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1
Mohammad Shah, Syed Tahir, Mohammad Farooq, Nadia Akbar, and Majid Bahir Mughal. "Subinguinal Cremasteric Disruption and Venous Ligation for Varicocele Repair." Pakistan Journal of Medical and Health Sciences 15, no. 5 (May 30, 2021): 943–46. http://dx.doi.org/10.53350/pjmhs21155943.
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Aim: To evaluate the outcome of subinguinal cremasteric disruption and venous ligation for the treatment of varicocele with regard to improvement in semen parameters, recurrence hydrocele formation and testicular atrophy. Methods: The clinical study was carried out from July 2016 to June 2019. Fifty-nine patients were included in the study. Varicocele repair was done as a day case surgery under local anesthesia using cremasteric disruption and venous ligation technique. The treatment outcomes studied were improvement in semen parameters and complications like recurrence, hydrocele formation and testicular atrophy. Results: Seventy-four varicocelectomies were done in fifty-nine patients. Semen parameters improved in those nineteen patients who had abnormal semen parameters before surgery and nine out of these nineteen (47.36%) got their semen count normal after varicocele repair. There were five recurrences (6.75%). No hydrocele formation or testicular atrophy occurred during one year of follow up. Conclusion: Day case varicocelectomy by subinguinal cremasteric disruption and venous ligation is a simple, economical choice with minimal morbidity and comparable outcomes. Keywords: Varicocele, Subinguinal cremasteric disruption and venous ligation, complication
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Zhang, Man-Li, Ling-Qian Wang, Yong Qi, Yi Wu, Dong-Hui Zhou, and Lu-Lin Li. "Comparative genomic analysis of three geographical isolates from China reveals high genetic stability of Plutella xylostella granulovirus." PLOS ONE 16, no. 1 (January 14, 2021): e0243143. http://dx.doi.org/10.1371/journal.pone.0243143.
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In this study, the genomes of three Plutella xylostella granulovirus (PlxyGV) isolates, PlxyGV-W and PlxyGV-Wn from near Wuhan and PlxyGV-B from near Beijing, China were completely sequenced and comparatively analyzed to investigate genetic stability and diversity of PlxyGV. PlxyGV-W, PlxyGV-B and PlxyGV-Wn consist of 100,941bp, 100,972bp and 100,999bp in length with G + C compositions of 40.71–40.73%, respectively, and share nucleotide sequence identities of 99.5–99.8%. The three individual isolates contain 118 putative protein-encoding ORFs in common. PlxyGV-W, PlxyGV-B and PlxyGV-Wn have ten, nineteen and six nonsynonymous intra isolate nucleotide polymorphisms (NPs) in six, fourteen and five ORFs, respectively, including homologs of five DNA replication/late expression factors and two per os infectivity factors. There are seventeen nonsynonymous inter isolate NPs in seven ORFs between PlxyGV-W and PlxyGV-B, seventy three nonsynonymous NPs in forty seven ORFs between PlxyGV-W and PlxyGV-Wn, seventy seven nonsynonymous NPs in forty six ORFs between PlxyGV-B and PlxyGV-Wn. Alignment of the genome sequences of nine PlxyGV isolates sequenced up to date shows that the sequence homogeneity between the genomes are over 99.4%, with the exception of the genome of PlxyGV-SA from South Africa, which shares a sequence identity of 98.6–98.7% with the other ones. No events of gene gain/loss or translocations were observed. These results suggest that PlxyGV genome is fairly stable in nature. In addition, the transcription start sites and polyadenylation sites of thirteen PlxyGV-specific ORFs, conserved in all PlxyGV isolates, were identified by RACE analysis using mRNAs purified from larvae infected by PlxyGV-Wn, proving the PlxyGV-specific ORFs are all genuine genes.
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Amiewalan, Florence O., and Frankie O. Balogun. "Foraminiferal analysis of AE-1 well, Agbada formation Onshore, Western Niger Delta Basin: Implication for biozonation and age dating." Global Journal of Pure and Applied Sciences 26, no. 2 (November 2, 2020): 107–18. http://dx.doi.org/10.4314/gjpas.v26i2.3.
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Foraminiferal and sedimentological analysis was carried out using ditch cutting samples from intervals 2700 ft. - 10,185 ft. in AE-1 well. The samples were composited at 60 ft. into ninety four (94) ditch cutting samples. The standard micropaleontological sample procedures to recover the foraminiferal biofacies assemblages was utilized, followed by analysis and interpretation of the obtained results. The sedimentological analysis reveals five lithofacies - sandstone, sandy shale, shaly sand, mudstone and sandy clay which constitute part of the Agbada Formation of the Niger Delta. The foraminiferal fauna recovered from the samples studied comprised of twenty four species grouped into nineteen genera from niniteen families and nineteen subfamilies. A few number of miscellaneous microfossils such as Ostracoda, Holothuroidea and Echinoderm remains were recovered. The total count of foraminiferal defined from this well is four hundred and nineteen (419). The planktic foraminiferal count was two hundred and forty two (242) (57.8 % of the total count) while the benthics foraminiferal count was one hundred and seventy seven (177) (42.2 % of the total count). Among the benthic forms, the calcareous consists of one hundred and forty nine forms (149) (33.4 % of the total benthic count) while the agglutinating benthic forms were thirty seven (37) (8.8 % of the total benthic count). One (1) planktic (Chiloguembelinacubensis) and three (3) benthic (Eponidesberthelotianus, Hanzawaiastratonii and Nonionellaauris) informal foraminiferal zones were established in the well. The age of the AE-1 well sediments has been interpreted to belong to Early Oligocene - Early Miocene in comparism with foraminiferal markers species whose stratigraphic ranges are well established in the Niger Delta and globally. This inferred the presence of the Rupelian - Burdigalian sediments in the Niger Delta.
Keywords: Foraminiferal, Biozone, Age, Rupelian, Burdigalian.
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Nordin, Peter, and Bo Stenquist. "Five-year results of curettage-cryosurgery for 100 consecutive auricular non-melanoma skin cancers." Journal of Laryngology & Otology 116, no. 11 (November 2002): 893–98. http://dx.doi.org/10.1258/00222150260369390.
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Large excisions or Mohs’ micrographic surgery (MMS) are often the suggested treatments for non-melanoma skin cancers (NMSCs) of the external ear. This five-year follow-up attempts to evaluate whether curettage-cryosurgery could be an alternative therapy for selected auricular NMSCs.One hundred auricular NMSCs, selected at a skin tumour clinic, were treated by a thorough curettage, with different-sized curettes, followed by cryosurgery in a double freeze-thaw cycle. Seventy-seven basal cell carcinomas (BCCs), 13 squamous cell carcinomas (SCCs), six SCCs in situ, and four basosquamous carcinomas were included. The mean diameter of the tumours was 18 mm (range 5–70). Morphoeiform BCCs, recurrent BCCs with fibrotic component, and most of the SCCs were selected for MMS.Seventy-one patients with 81 tumours were followed-up for at least five years with only one recurrence. Nineteen patients with 19 tumours, followed-up for two to four years, died from other causes with no sign of recurrence at their last visit. Patients followed-up for less than two years were excluded. No major problems were registered after treatment. The cosmetic result was good or acceptable in most patients.In carefully selected patients a thorough curettage followed by freezing with liquid nitrogen in a double freeze-thaw cycle could be a safe and inexpensive therapy even for large NMSCs of the external ear.
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Hakel-Smith, Nancy, and Paula Ritter-Gooder. "Content Validation of Defining Characteristics of Nineteen Prevalent Nutrition Diagnoses in Adult Hospitalized Patients." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 1125. http://dx.doi.org/10.1093/cdn/nzaa055_010.
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Abstract Objectives To validate the content of 19 prevalent nutrition diagnoses (NDs), 17 from the Nutrition Care Process Terminology (NCPT) and two other NDs, identified by Clinical Registered Dietitian Nutritionists (CRDN) in an acute-care hospital and identify critical defining characteristics (signs and/or symptoms). Methods Using a descriptive research design with survey methodology, a ND Validation Instrument was completed by seven CRDNs with knowledge of NDs. Each ND included a label, a definition, and a mean number of 14 defining characteristics (range 1–33). CRDNs were asked to read labels, definitions and think about adult hospitalized patients and use a 4-point Likert scale (very, quite, very little, and not at all characteristic) to rate the 264 defining characteristics. Diagnostic content validity (DCV) scores using weighted means were calculated. Critical defining characteristics were identified with a DCV score of ≥0.80. Results The CRDNs had 13.29 ± 5.09 years of clinical experience and 12.57 ± 5.26 years using NDs at the study site. Seventy-one % of the CRDNs held a graduate degree. The DCV scores of 264 critical characteristics ranged from 0.32 to 1.00. Twenty-four % (n = 64) of the characteristics were validated with a mean of 3.36 critical characteristics per diagnosis (range: 1–10). Eighty-nine % (n = 57) of the critical characteristics were in three of the five NCPT assessment categories: (Food/Nutrition-Related History; Anthropometric measurements and Nutrition-focused physical findings. Conclusions Content validation of 19 NDs resulted in the identification of 24% (N = 64) of characteristics as valid with 89% (N = 57) clustered in three of the five NCPT assessment categories. The low content validity of 76% (N = 200) of the characteristics suggests that the criteria are not representative or consistent with the definitions of the NDs. Identification of a minimum number of critical characteristics and assessment categories for each diagnosis will make it easier for CRDNs to learn the signs/symptoms and to recognize them when present in patients, to make an accurate diagnosis. Further validation studies with larger samples and various patient populations, nationally and internationally, are needed to refine critical characteristics and assessment categories. Funding Sources None.
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Wilcock, B. P., and R. L. Peiffer. "Morphology and Behavior of Primary Ocular Melanomas in 91 Dogs." Veterinary Pathology 23, no. 4 (July 1986): 418–24. http://dx.doi.org/10.1177/030098588602300411.
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Primary ocular melanocytic neoplasms from 91 dogs were divided into two groups by histologic criteria. Seventy-five were benign and composed of spindle-shaped and large polyhedral melanocytes similar to those of human ocular melanocytomas. Fifty-nine of these originated in the uvea where most resulted in uveitis, glaucoma, or hyphema prior to enucleation. None metastasized. Nineteen melanocytomas were limbal tumors. None metastasized, but three of nine incompletely excised tumors were found within the anterior chamber 2 to 3 years after the initial removal. Sixteen uveal melanocytic neoplasms were histologically malignant. Three had confirmed metastases, all within 3 months of enucleation. Cell type or pattern of growth within the globe were not predictive of biologic behavior. Our data suggest that the mitotic index is the best criterion for histologic identification of ocular melanomas with high metastatic potential. We propose that the classification of primary ocular melanomas be simplified to include only two categories: melanocytoma (benign) and melanoma (potentially malignant). Further behavioral data may justify a grading scheme for melanomas based upon mitotic index.
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Hølmebakk, T., and A. Nesbakken. "Surgery for Pilonidal Disease." Scandinavian Journal of Surgery 94, no. 1 (March 2005): 43–46. http://dx.doi.org/10.1177/145749690509400111.
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Background and Aims: Surgery for pilonidal disease carries a considerable risk of complications, recurrence, and cosmetic sequelae. The present study evaluates the four procedures performed in our institution. Material and Methods: Operations from 1999 through 2002 were retrospectively assessed. Cosmetic result and overall satisfaction were reported on visual analogue scales. Results: Seventy-three procedures were performed in 71 patients: excision with open granulation in nine; excision and primary suture in 25; rhomboid plasty in 23; and lay-open in 16 patients. Infections were as frequent after rhomboid plasty (40 %) as after excision and primary suture (43 %). Nineteen recurrences (26 %) were observed during a median follow-up of 20 months, and the estimated five-year actuarial recurrence rate was 44 %. Recurrence occurred in 1/9 (11 %) after excision with granulation, in 4/23 (17 %) after excision and suture, in 5/25 (20 %) after rhomboid plasty, and in 9/16 patients (56 %) after lay-open. The cosmetic result was satisfactory only in 22/53 (42 %) patients; the result was poor in 16/53 (30 %) patients. Conclusion: Results after surgery for pilonidal disease are modest and should be compared to conservative management in a randomised trial.
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Biscotti, Nello, and Andrea Pieroni. "The hidden Mediterranean diet: wild vegetables traditionally gathered and consumed in the Gargano area, Apulia, SE Italy." Acta Societatis Botanicorum Poloniae 84, no. 3 (2015): 327–38. http://dx.doi.org/10.5586/asbp.2015.031.
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<p>Despite the extensive bio-scientific literature concerning the Mediterranean diet, which emerged in the last three decades, systematic ethnography-centered investigations on a crucial portion of this food system, linked to the traditional consumption of non-cultivated vegetables, are still largely lacking in many areas of the Mediterranean Basin.</p><p>In this research, an ethnobotanical field study focusing on wild vegetables traditionally gathered and consumed locally, was conducted in a few centers and villages located in the Gargano area, northern Apulia, SE Italy, by interviewing twenty-five elderly informants. The folk culinary uses of seventy-nine botanical taxa of wild vascular plants, belonging to nineteen families, were recorded, thus showing a remarkable resilience of traditional environmental knowledge (TEK) related to wild food plants. In particular, approximately one-fourth of the recorded wild vegetables are still very commonly gathered and consumed nowadays, while ten taxa have never been reported in previous ethnobotanical studies conducted in Southern Italy. These findings demonstrate the crucial cultural role played by folk cuisines in preserving TEK, despite significant socio-economic changes that have affected the study area during the past four decades.</p>
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Grimm, Jodi J., Matthew M. Wise, Mark H. Meissner, and Stephen C. Nicholls. "The Incidence of Popliteal Artery Aneurysms in Patients with Abdominal Aortic Aneurysms." Journal for Vascular Ultrasound 31, no. 2 (June 2007): 71–73. http://dx.doi.org/10.1177/154431670703100201.
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Purpose We sought to evaluate the incidence of popliteal artery aneurysms (PAAs) in patients who have a diagnosis of abdominal aortic aneurysm (AAA). Methods It has been previously documented that patients with AAA have a greater incidence of PAA. During the past 11 years, 163 patients presented to the Vascular Laboratory at Harborview Medical Center with an AAA. Seventy-one (44%) of these patients had popliteal arteries evaluated using duplex ultrasound (Advanced Technology Laboratory 3000, 5000, 9000). The popliteal artery was measured in the anteroposterior and transverse diameters. A PAA was defined as an artery larger than 1.5 cm and/or an ectatic artery with thrombus present. Results Fourteen patients had a PAA; six patients (43%) had PAA bilaterally, for a total of 20 aneurysms. Nineteen (95%) aneurysms had thrombus present. Various interventional treatments were used: five limbs (25%) received an arterial bypass graft, two (10%) underwent amputation, and two (10%) received thrombolytic therapy Conclusions There is a high incidence of PAA in patients with AAA (19.7% in this series). Patients with a diagnosis of AAA should be screened for PAA and considered for elective repair to prevent the high rate of complications associated with these lesions.
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Pereira-Lorenzo, S., J. Fernández-López, and J. Moreno-González. "Variability and Grouping of Northwestern Spanish Chestnut Cultivars. II. Isoenzyme Traits." Journal of the American Society for Horticultural Science 121, no. 2 (March 1996): 190–97. http://dx.doi.org/10.21273/jashs.121.2.190.
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Two-hundred and ninety-five trees sampled from seventy-five local chestnut (Castanea sativa Mill.) cultivars in northwestern Spain, which had been previously studied morphologically, were further analyzed for five isoenzyme systems, encoded by seven loci. Objectives of this study were to 1) describe the intracultivar and intercultivar variability by isoenzyme analysis and to compare it with the morphological variation and 2) establish a classification of the cultivars and to discuss its relation to the morphological classification. Variability within and among cultivars was detected, confirming the previous morphological results. The level of the observed heterozygosity in this Spanish population was higher than expected and also higher than that found in other European populations. Because of the great diversity discovered, this material seems to be worthy for introducing and maintaining in a germplasm bank. Nineteen main clusters were identified for the twenty-three most widely distributed cultivars. On the average, 61% of the trees belonging to a specific cultivar was included in the same cluster. The remaining 39% was scattered in other clusters, which indicates intracultivar variability. Therefore there is opportunity for selection within cultivars. Two clusters included three important cultivars each. This suggests possible synonymies. No correlation between morphological traits and the isoenzymic alleles was detected. The isoenzyme technique identified a higher number of cultivars increasing the information obtained with morphological traits. Correlations between the frequency of some of the alleles and the altitude and other environmental variables suggest that selection of the best adapted genotypes has occurred.
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Gill, K. S., E. L. Lubbers, B. S. Gill, W. J. Raupp, and T. S. Cox. "A genetic linkage map of Triticum tauschii (DD) and its relationship to the D genome of bread wheat (AABBDD)." Genome 34, no. 3 (June 1, 1991): 362–74. http://dx.doi.org/10.1139/g91-058.
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One hundred and seventy-eight loci have been mapped in Triticum tauschii (Coss.) Schmal. (2n = 14, DD) and Triticum aestivum L. em. Thell. (2n = 42, AABBDD). Thirty-five loci were mapped by aneuploid analysis in T. aestivum. One hundred and fifty-two loci, including 143 restriction fragment length polymorphisms (RFLPs), 8 proteins, and 1 leaf rust resistance gene, were mapped in an F2 population (60 plants) of T. tauschii. One hundred and twenty-seven loci were placed in linkage groups belonging to seven D-genome chromosomes of T. tauschii. The source of the probes was a PstI genomic library of T. tauschii, which gave 13% single-low copy clones. Four restriction endonucleases (DraI, EcoRI, EcoRV, HindIII) gave 75% polymorphism between the two parents. Nineteen clones detected multiloci ranging from two to nine in number. Deletions–insertions and point mutations were equally important for generating RFLPs. A hypervariable sequence was identified, which may have potential use in varietal fingerprinting. One marker was found to be linked to a rust-resistance gene. The map will be useful for determining genetic relationships in the Triticeae and for tagging genes of economic importance.Key words: restriction fragment length polymorphism, Triticum aestivum, leaf rust, isozymes, Aegilops squarrosa.
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Woollacott, Marjorie H., Anne Shumway-Cook, and Lewis M. Nashner. "Aging and Posture Control: Changes in Sensory Organization and Muscular Coordination." International Journal of Aging and Human Development 23, no. 2 (September 1986): 97–114. http://dx.doi.org/10.2190/vxn3-n3rt-54jb-x16x.
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The following study examined two aspects of balance control in the older adult: 1) the coordination of the timing and the amplitude of muscle responses to postural perturbations, and 2) the ability of the participant to reorganize sensory inputs and subsequently modify postural responses as a consequence of changing environmental conditions. Coordination of muscle activity in postural responses of twelve elderly (sixty-one to seventy-eight years) participants were compared to those of young (nineteen to thirty-eight years) adults using a movable platform and recording the electromyographic activity of muscles of the legs. The following changes were noted in the timing and amplitude of muscle activity within a postural response synergy: 1) increases in the absolute latency of distal muscle responses were observed in all older adults; 2) in five of the twelve older adults temporal reversals of proximal and distal muscle response onset were observed; and 3) there was a breakdown in the correlation of the amplitude of responses within a synergy. The ability of the older adult to balance under conditions of reduced or conflicting sensory information was also impaired. When confronted with functionally inappropriate visual and/or somatosensory inputs, half of the older group lost balance. In most instances, however, the older participants were able to maintain stability during subsequent responses to conflicting stimuli.
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Baghlaf, Khlood, Vanessa Muirhead, and Cynthia Pine. "Relationships between children’s sugar consumption at home and their food choices and consumption at school lunch." Public Health Nutrition 23, no. 16 (January 20, 2020): 2941–49. http://dx.doi.org/10.1017/s1368980019003458.
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AbstractObjective:To investigate the relationships between children’s food and drink choices at school lunch for children who consume high and low sugar intakes at home.Design:Children’s food and drink consumption at home was assessed using diet diaries over three consecutive days. Children were classified as ‘high’ or ‘low’ sugar consumers at home using the WHO recommendation that free sugars should be less than 10 % of their daily total energy intake. A purposive sample of children was then selected and observed during school lunch, recording food selections, food left on plates and content of packed lunches.Setting:Six primary schools in Newham and Kent, England.Participants:Parents and children aged 6–7 years.Results:Seventy-one parents completed diet diaries. From the seventy-one, thirty-nine children were observed during school lunch. Twenty children were high sugar consumers, nineteen children were low sugar consumers; thirty-one children had a school meal. Eleven of the fifteen children (73 %) who had school meals and who were high sugar consumers selected a high-sugar dessert rather than fruit. Only five of the sixteen (31 %) children who had school meals and were low sugar consumers at home chose a high-sugar dessert. Most of the children who had packed lunches had sweet items, despite school policies.Conclusions:Children who consumed high sugar intake at home tended to select foods high in sugar for school meals or had packed lunches containing high-sugar foods. The implications for public health programmes include healthy eating workshops and implementing school food policies.
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Ramaswamy, Srinivas V., Amol G. Amin, Servet Göksel, Charles E. Stager, Shu-Jun Dou, Hana El Sahly, Soraya L. Moghazeh, Barry N. Kreiswirth, and James M. Musser. "Molecular Genetic Analysis of Nucleotide Polymorphisms Associated with Ethambutol Resistance in Human Isolates ofMycobacterium tuberculosis." Antimicrobial Agents and Chemotherapy 44, no. 2 (February 1, 2000): 326–36. http://dx.doi.org/10.1128/aac.44.2.326-336.2000.
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ABSTRACT Ethambutol (EMB) is a central component of drug regimens used worldwide for the treatment of tuberculosis. To gain insight into the molecular genetic basis of EMB resistance, approximately 2 Mb of five chromosomal regions with 12 genes in 75 epidemiologically unassociated EMB-resistant and 33 EMB-susceptible Mycobacterium tuberculosis strains isolated from human patients were sequenced. Seventy-six percent of EMB-resistant organisms had an amino acid replacement or other molecular change not found in EMB-susceptible strains. Thirty-eight (51%) EMB-resistant isolates had a resistance-associated mutation in only 1 of the 12 genes sequenced. Nineteen EMB-resistant isolates had resistance-associated nucleotide changes that conferred amino acid replacements or upstream potential regulatory region mutations in two or more genes. Most isolates (68%) with resistance-associated mutations in a single gene had nucleotide changes in embB, a gene encoding an arabinosyltransferase involved in cell wall biosynthesis. The majority of these mutations resulted in amino acid replacements at position 306 or 406 of EmbB. Resistance-associated mutations were also identified in several genes recently shown to be upregulated in response to exposure of M. tuberculosis to EMB in vitro, including genes in theiniA operon. Approximately one-fourth of the organisms studied lacked mutations inferred to participate in EMB resistance, a result indicating that one or more genes that mediate resistance to this drug remain to be discovered. Taken together, the results indicate that there are multiple molecular pathways to the EMB resistance phenotype.
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BRASHEARS, M. M., D. JARONI, and J. TRIMBLE. "Isolation, Selection, and Characterization of Lactic Acid Bacteria for a Competitive Exclusion Product To Reduce Shedding of Escherichia coli O157:H7 in Cattle." Journal of Food Protection 66, no. 3 (March 1, 2003): 355–63. http://dx.doi.org/10.4315/0362-028x-66.3.355.
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Lactic acid bacteria (LAB) were selected on the basis of characteristics indicating that they would be good candidates for a competitive exclusion product (CEP) that would inhibit Escherichia coli O157:H7 in the intestinal tract of live cattle. Fecal samples from cattle that were culture negative for E. coli O157:H7 were collected. LAB were isolated from cattle feces by repeated plating on deMan Rogosa Sharpe agar and lactobacillus selection agar. Six hundred eighty-six pure colonies were isolated, and an agar spot test was used to test each isolate for its inhibition of a four-strain mixture of E. coli O157:H7. Three hundred fifty-five isolates (52%) showed significant inhibition. Seventy-five isolates showing maximum inhibition were screened for acid and bile tolerance. Most isolates were tolerant of acid at pH levels of 2, 4, 5, and 7 and at bile levels of 0.05, 0.15, and 0.3% (oxgall) and were subsequently identified with the API system. Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus delbreukii, Lactobacillus salivarius, Lactobacillus brevis, Lactobacillus cellobiosus, Leuconostoc spp., and Pediococcus acidilactici were the most commonly identified LAB. Nineteen strains were further tested for antibiotic resistance and inhibition of E. coli O157:H7 in manure and rumen fluid. Four of these 19 strains showed susceptibility to all of the antibiotics, 13 significantly reduced E. coli counts in manure, and 15 significantly reduced E. coli counts in rumen fluid (P < 0.05) during at least one of the sampling periods. One of the strains, M35, was selected as the best candidate for a CEP. A 16S rRNA sequence analysis of M35 revealed its close homology to Lactobacillus crispatus. The CEP developed will be used in cattle-feeding trials.
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Friedmann, Alison M., Melissa M. Hudson, Howard J. Weinstein, Sarah S. Donaldson, Larry Kun, Nancy J. Tarbell, and Michael P. Link. "Treatment of Unfavorable Childhood Hodgkin’s Disease With VEPA and Low-Dose, Involved-Field Radiation." Journal of Clinical Oncology 20, no. 14 (July 15, 2002): 3088–94. http://dx.doi.org/10.1200/jco.2002.03.051.
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PURPOSE: Between January 1990 and April 1993, 56 pediatric patients with Hodgkin’s disease were treated on a single-arm trial at three institutions with a regimen designed to maintain high cure rates while minimizing the potential late effects of treatment, such as infertility, second malignant neoplasms, and cardiopulmonary injury. PATIENTS AND METHODS: The regimen used combined-modality therapy with six cycles of vinblastine, etoposide, prednisone, and doxorubicin (VEPA) chemotherapy and low-dose, involved-field radiation. Unfavorable features comprised bulky presentations of localized (stage I or II) disease or advanced (stage III or IV) Hodgkin’s disease. RESULTS: Of 56 patients enrolled, 26 (46%) had unfavorable presentations of stage I/II disease and 30 (54%) had advanced (stage III/IV) disease. Seventy-nine percent of the patients are alive without disease at a median follow-up time of 8.9 years from diagnosis. Nineteen patients had events at a median of 1.5 years (range, 0.4 to 7.9 years) from diagnosis; 17 patients relapsed, one died of cardiomyopathy, and one died of accidental injuries. Survival and event-free survival (EFS) estimates at 5 years for the entire cohort were 81.9% (SE, 5.2%) and 67.8% (SE, 6.3%), respectively. Five-year EFS by stage was 100% for stage I, 79.2% (SE, 8.3%) for stage II, 70% (SE, 14.5%) for stage III, and 49.5% (SE, 11.3%) for stage IV patients. CONCLUSION: Combined-modality therapy with VEPA chemotherapy and low-dose, involved-field radiation is adequate for disease control of early-stage patients with unfavorable features, but it is inferior to other standard regimens for advanced-stage patients.
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Walker, Evan Justin, Ryan Mcmahan, Deborah Barnes, Mary Katen, Daniela Lamas, and Rebecca Sudore. "Who, what, where, when, and how? Advance care planning documentation practices and accessibility in the electronic health record." Journal of Clinical Oncology 35, no. 31_suppl (November 1, 2017): 2. http://dx.doi.org/10.1200/jco.2017.35.31_suppl.2.
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2 Background: Documenting patients’ advance care planning (ACP) wishes is essential to providing value aligned care, as is having this documentation readily accessible. Early ACP is increasingly being recognized as integral to oncologic care, however, little is known about current documentation practices. In this cross-sectional study, we describe ACP documentation practices and accessibility of documented ACP discussions in the electronic health record (EHR). Methods: Participants were recruited from outpatient clinics at the San Francisco VA, were ≥60 years old, with ≥2 chronic/serious conditions and ≥2 primary care visits in the past year. ACP documentation was abstracted from the EHR in 2013-2015 and included any prior legal forms/orders and ACP discussions documented within the prior five years. Frequency and type of ACP documentation was calculated using percentages and means. For discussions, author discipline and location of documentation was determined. Discussions were deemed “accessible” if documented in a designated ACP posting location or “not easily accessible” if recorded as free text in progress notes. Results: The mean age of 414 participants was 71 years (SD ± 8), 9% were women, 43% were non-white, and 51% had documented ACP including 149 (36%) with ACP forms and 138 (33%) with ACP discussions. Seventy-five (54%) discussions were documented by social workers and 49 (36%) by primary care providers. However, 76 (55%) discussions were not easily accessible. For 27 (18%) participants with advance directives, subsequent discussions documented a change in treatment preferences. Nineteen (70%) discussions reporting a change in wishes were not easily accessible. Conclusions: Half of chronically ill, older patients had documented ACP wishes, including a third with documented ACP discussions. Most discussions were documented by social workers and were not easily accessible, although discussions often represented changes from prior advance directives. Clinician education and EHR changes to ensure documented discussions are accessible are important patient-safety and quality improvement targets to ensure patients’ wishes are honored.
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Rubin, C. M., L. L. Robison, J. D. Cameron, W. G. Woods, M. E. Nesbit, W. Krivit, T. H. Kim, R. D. Letson, and N. K. Ramsay. "Intraocular retinoblastoma group V: an analysis of prognostic factors." Journal of Clinical Oncology 3, no. 5 (May 1985): 680–85. http://dx.doi.org/10.1200/jco.1985.3.5.680.
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A retrospective analysis of the University of Minnesota (Minneapolis) experience with retinoblastoma is presented. Seventy-five patients were diagnosed with retinoblastoma between 1958 and 1983, of which 53 (71%) had at least one Reese-Ellsworth group V eye. Nineteen group V patients and one group II patient developed extraocular disease recurrence. The cumulative actuarial rate of recurrence at 12 years was 36% for patients with group V disease. The median time from diagnosis to recurrence for unilateral patients was seven months and for bilateral patients 28 months (P = .001). Patients developing extraocular disease had a 10-year actuarial survival rate postrecurrence of 34%. The four long-term survivors of extraocular recurrences had had isolated orbital or local soft tissue recurrences only. Features of group V patients associated with extraocular recurrences were identified by univariate life table analyses. Clinical poor-risk factors included the nongenetic form of the disease (P = .03) and male sex (P = .02). Pathologic poor risk factors included rubeosis (P = .01), undifferentiated histology (P = .03), large tumor size (P = .05), and intraocular extension to the anterior segment (P = .02), retinal pigment epithelium (P = .03), choroid (P less than .001), and optic nerve beyond the lamina cribrosa (P = .02). Treatment-associated poor-risk factors included an optic nerve length of less than 5 mm removed at enucleation (P = .003). Multivariate life table analyses demonstrated the following parameters to be independent poor-prognostic factors: optic nerve length of less than 5 mm removed at enucleation (P = .001), optic nerve involvement (P = .004), and large tumor size (P = .01). These results will help to identify patients with retinoblastoma who are at greatest risk for extraocular recurrence.
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Frankel, A. E., M. A. Weir, P. D. Hall, M. Holguin, C. Cable, D. A. Rizzieri, and D. E. Hogge. "Induction of remission in patients with acute myeloid leukemia without prolonged myelosuppression using diphtheria toxin-interleukin 3 fusion protein." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 7068. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.7068.
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7068 The recombinant diphtheria toxin fusion protein, DT388IL3, composed of the catalytic and translocation domains of diphtheria toxin (DT388) fused to human interleukin-3 (IL3) showed selective cytotoxicity to acute myeloid leukemia (AML) stem cells both in vitro and in vivo and was prepared for a phase I clinical study (Urieto, Protein Exp Purif 33, 123, 2004). FDA approval (BB IND#11314) and IRB approvals were obtained. Seventy-five AML patients were screened and thirty-one patients treated. The median age of treated patients was 62 years (range, 25- 81 years). There were sixteen males and fifteen females. Disease was de novo in three, first relapse in ten, second relapse in eight, and refractory in ten patients. Four patients had a history of MDS, and one had a history of secondary AML. One patient each had previously received an autologous or allogeneic stem cell transplant. Cytogenetics were unfavorable in ten, intermediate in nineteen, and not done in two. Seven patients were treated with 4 μg/kg, eight patients were treated with 5.3 μg/kg, thirteen patients treated with 7.1 μg/kg, and three patients treated with 9.4 μg/kg DT388IL3. Drug-related toxicities were mild to moderate and transient including fever, chills, hypotension, hypoxemia, and hypoalbuminemia. Consistent with an absence of toxicity to normal hematopoietic progenitors, responses occurred in the absence of prolonged myelosuppression. Among thirty evaluable patients, we have observed one CR of 8 months duration, two partial remissions (PRs) lasting one and three months and three minimal responses with clearance of peripheral blasts and marrow blast cytoreductions of 89%, 90% and 93% lasting one to two months. Dose escalation is proceeding. No significant financial relationships to disclose.
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Hassan, Mahmuda, Ferdousi Choudhury, Marium Begum, Hamidur Rahman, and Sayeba Akhter. "Immediate Perinatal Outcome of Neonates with Maternal Hypertensive Disorders in Pregnancy." Journal of Nepal Paediatric Society 33, no. 3 (December 15, 2013): 190–95. http://dx.doi.org/10.3126/jnps.v33i3.9252.
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Introduction: Hypertensive disorders of pregnancy seem to be one of the major causes of maternal morbidity and mortality leading to 10-15% of maternal deaths especially in the developing world. This study examines the perinatal outcome of neonates with mothers having hypertensive disorder of pregnancy. Materials and Methods: Seventy three mothers and their newborn babies were selected. Mothers with Gestational hypertension, preeclampsia, eclampsia, chronic hypertension, preeclampsia superimposed on chronic hypertension were included. Gestational diabetics (GDM), chronic maternal diseases, infant of diabetic mother (IDM), babies with major congenital malformations were excluded. Results: Thirty five mothers (47.9%) had regular antenatal check up (ANC) and 38 (52%) had irregular. Nineteen mothers (26%) were primipara and 54 (74%) were multipara. Forty four mothers (60%) had positive family history or had own history of hypertensive disorder during their previous pregnancy. 13 mothers (17.8%) had normal vaginal delivery (NVD), 60 mothers (82.19%) had lower uterine cesarean section (LUCS). 30 babies (41%) were admitted. 44 mothers (60%) had gestational hypertension, 21 had (28.6%) pre-eclamtic toxemia (PET), 3 had (4.1%) eclampsia, 5 had (6.8%) essential hypertension 3 of them subsequently developed PET. Mean maternal age 26.86 years, gestational age 34.15 (±1.46)weeks among admitted and 36.30 (±1.6)weeks among non-admitted group. Mean birth weight was 1.69 (±0.39) kg. among admitted and 2.71 (±0.31) kg. in non-admitted babies. Seven pregnancies (9.58%) were twin, macerated 1 twin among was among 2 pregnancies (2.7%), 5 intra uterine death (IUD) observed in single pregnancy. Conclusion: Significant number of babies with maternal hypertensive disorder of pregnancy needed hospitalization, mean birth weight and gestational age was less than that of the non-admitted group. DOI: http://dx.doi.org/10.3126/jnps.v33i3.9252 J. Nepal Paediatr. Soc. 2013;33(3):190-195
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Radzak, Kara. "Concussion prevention strategies: A Survey of division I and division II female soccer teams." Neurology 93, no. 14 Supplement 1 (September 30, 2019): S5.3—S6. http://dx.doi.org/10.1212/01.wnl.0000580876.33479.c5.
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ObjectiveThe purpose of this study is to evaluate concussion prevention strategies being used in NCAA Division I and Division II women's soccer and characterize the beliefs of Certified Athletic Trainers (ATs) on concussion prevention methods.BackgroundWhile much attention has been paid to decreasing concussion rates in collegiate woman's soccer, it is unknown what prevention strategies are currently being performed. Additionally, ATs’ beliefs on the efficacy of concussion prevention practices for these athletes is unknown.Design/MethodsParticipants included ATs employed at any of the 334 Division I or 273 Division II universities working with woman's soccer. A survey instrument of structured questions followed by open-ended follow up questions was developed to identify if teams utilized cervical strengthening programs, headgear, or other techniques for concussion prevention. Questions also address ATs' beliefs on the effectiveness of cervical strengthening, headgear and mouthguards in concussion prevention. Data were collected via questionnaire e-mailed through Qualtrics survey software. Responses were received from 222 ATs (37.8% response rate). Data were analyzed via descriptive statistics.ResultsSome form of cervical strengthening or stability for concussion prevention was performed by 38 teams (17.12%) and seven (3.15%) were unsure. The majority (69.86%) believe such programs will aid in concussion prevention. Equipment for concussion prevention was report by 36 (16.59%). Text responses included mouthpieces (n = 3) and headgear (n = 31). Seventy-eight (35.49%) reported players on their team wear headgear. Nineteen (8.76%) believe headgear prevents concussions. Forty-five (20.74%) believe mouthguards prevent concussions. Proper soccer technique is implemented by 151 (69.59%) and 14 (0.06%) cite nutritional strategies for concussion prevention.ConclusionsAlthough most ATs believe that cervical strengthening aids concussion prevention, few programs are implementing this strategy. Disconnect exists between available evidence and the perceptions held by ATs regarding mouthguards and headgear for concussion prevention.
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Pecundo, Melissa H., Thomas Edison E. dela Cruz, Tao Chen, Kin Israel Notarte, Hai Ren, and Nan Li. "Diversity, Phylogeny and Antagonistic Activity of Fungal Endophytes Associated with Endemic Species of Cycas (Cycadales) in China." Journal of Fungi 7, no. 7 (July 18, 2021): 572. http://dx.doi.org/10.3390/jof7070572.
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The culture-based approach was used to characterize the fungal endophytes associated with the coralloid roots of the endemic Cycas debaoensis and Cycas fairylakea from various population sites in China. We aim to determine if the assemblages of fungal endophytes inside these endemic plant hosts are distinct and could be explored for bioprospecting. The isolation method yielded a total of 284 culturable fungal strains. Identification based on the analysis of the internal transcribed spacer (ITS) rDNA showed that they belonged to two phyla, five classes, eight orders and 22 families. At least 33 known genera and 62 different species were confirmed based on >97% ITS sequence similarity. The most frequent and observed core taxa in the two host species regardless of their population origin were Talaromyces, Penicillium, Fusarium, Pochonia and Gliocladiopsis. Seventy percent was a rare component of the fungal communities with only one or two recorded isolates. Contrary to common notions, diversity and fungal richness were significantly higher in C. debaoensis and C. fairylakea collected from a botanical garden, while the lowest was observed in C. debaoensis from a natural habitat; this provides evidence that garden management, and to a minor extent, ex-situ conservation practice, could influence fungal endophyte communities. We further selected nineteen fungal isolates and screened for their antagonistic activities via a co-cultivation approach against the phytopathogens, Diaporthe sp. and Colletotrichum sp. Among these, five isolates with high ITS similarity matches with Hypoxylon vinosupulvinatum (GD019, 99.61%), Penicillium sp. (BD022, 100%), Penicillifer diparietisporus (GD008, 99.46%), Clonostachys rogersoniana (BF024, 99.46%) and C. rosea (BF011, 99.1%), which showed exceptional antagonistic activities against the phytopathogenic fungi with a significant inhibition rate of 70–80%. Taken together, our data presented the first and most comprehensive molecular work on culturable fungal endophytes associated with the coralloid roots of cycads. Our study also demonstrated that about 5% of fungal endophytes were not detected by the high-throughput sequencing approach, implying the equal importance of a culture-dependent approach to study fungal communities of cycads. We further highlighted the potential role of endemic and rare plants to discover and isolate unique plant-associated fungal taxa with excellent biocontrol properties.
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Shrestha, Bikash lal. "Informed Consent In Patients Undergoing ENT Surgery: What Do Patients Want To Know?" Philippine Journal of Otolaryngology-Head and Neck Surgery 25, no. 2 (December 3, 2010): 18–22. http://dx.doi.org/10.32412/pjohns.v25i2.623.
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Objective: To determine patient satisfaction with the informed consent process in ear, nose and throat (ENT) diseases requiring surgery. Specifically, to determine relationships between educational levels of patients and their satisfaction with information given by doctors versus self-gathered information; whether complications of the operation were explained to, and could be listed by patients; the types of complications patients expected to be informed about and the importance of this information to them; their familiarity with the term “informed consent” and their preference for written or spoken information; and whether they were convinced about what they consented to.
Methods:
Design: Cross-sectional Descriptive Study
Setting: Tertiary Public Hospital
Patients: One Hundred
Results: There were 55 males and 45 females (average age 26.7 years, range 4 - 74 years). Ten percent (all children) had no formal education, 56% had primary to high school education, 23% had certificate level education, and 11% had a baccalaureate or masters degree. Ninety-five percent claimed they knew what informed consent was. Ninety percent were satisfied with the information given to them by doctors. Eighty percent, mainly with educational levels of high school and above, preferred to receive written information from doctors. Twenty three percent accessed other sources of information. Those with certificate level education talked with previously operated patients (10%) or read magazines (2%), while the internet was favored by almost all of those with baccalaureate degrees (8%) and all those with masters degrees (2%). Of those who accessed self-gathered information, 21% were not satisfied while only 2% were satisfied. Seventy percent considered the information given by doctors very important. Similarly, seventy percent (mostly from the higher educational levels) considered the impact of information provided by the doctor completely convincing for decision making, while thirty percent (mostly from lower educational levels) only found the information partly convincing. Forty nine percent (again from the lower educational levels), could not list even a single complication. Nineteen percent, with educational levels of certificate and above, wanted to know all complications of surgery, including those that were very rare while fifty six percent wanted to know most of the complications.
Conclusion: We should not underestimate the importance of the outpatient consultation, the importance of written material and non medical information sources as patients’ expectations are quite high and the majority of them wanted to be informed about most complications. We should also find ways to improve the provision of patient information, and where possible and appropriate, as per specific patient groups.
Key words: Informed consent, otorhinolaryngology, surgical procedures
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Mäkelä, J. T., and M. Niskasaari. "Stoma Care Problems after Stoma Surgery in Northern Finland." Scandinavian Journal of Surgery 95, no. 1 (March 2006): 23–27. http://dx.doi.org/10.1177/145749690609500105.
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Background and Aims: Stoma-related complications and problems in stoma care are common after gastrointestinal surgery requiring the construction of a stoma. The frequency and types of such complications and problems were evaluated in a patient cohort operated on in Oulu University Hospital. Material and Methods: A detailed questionnaire concerning clinical problems and stoma care was mailed to 163 stoma patients operated on during the years from 1995 to 2001 in Oulu University Hospital. One hundred and nineteen patients (70 percent) answered the questions adequately. The clinical variables concerning stoma complications and the patients' symptoms, problems with stoma care and adaptation to the situation were recorded. Special attention was paid to the patients' general wellbeing and social problems. Results: Thirty-five patients (30%) had stoma complications, most commonly parastomal hernias (18 cases). Patients with an ileostomy had more difficulties with stoma handling more often than the patients with a colostomy. Seventy-eight patients (66%) were well adapted to their stoma, including 49 (72%) of the patients with a colostomy and 25 (56%) of the patients with an ileostomy. Of the 41 non-adapted patients, 12 did not accept their altered body image, ten had problems in social life and nine had difficulties because of faecal leakage. The quality of life analysis of 114 patients showed that their physical condition was better than before the operation in 55 cases (48%), unchanged in 16 (14%) and worse in 43 (38%). General mental health was better than before the operation in 52 cases (46%), unchanged in 23 (20%) and worse in 39 (34%) patients. Social functioning had improved after stoma surgery in 38 cases (34%), remained unchanged in 27 (24%) and deteriorated in 46 (42%) patients after stoma surgery. Patients with a colostomy reported worse subjective physical condition, mental health and social functioning than the patients with an ileostomy. Conclusions: Two-thirds of the patients had adapted to their stoma. The patients with an ileostomy had difficulties in stoma handling and the patients with a colostomy reported their physical, mental and social wellbeing to be affected.
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Lesho, Emil, Julie Ake, Xiao-Zhe Huang, Dana M. Cash, Mikeljon Nikolich, Melissa Barber, Kathleen Robens, Eric Garnett, Luther Lindler, and Paul Scott. "Amount of Usage and Involvement in Explosions Not Associated with Increased Contamination of Prehospital Vehicles with Multi-drug-resistant Organisms." Prehospital and Disaster Medicine 28, no. 2 (January 7, 2013): 107–9. http://dx.doi.org/10.1017/s1049023x12001781.
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AbstractIntroductionThe role of explosions and patient transport vehicles as sources and vectors of Gram-negative, multidrug-resistant organisms (MDROs) that predominate infections following lengthy evacuations after disasters due to natural hazards and in current war-trauma patients is unknown.Hypothesis/ProblemDamaged or heavily-used vehicles could be sources of the MDROs subsequently linked to nosocomial infections.MethodsFrom January through May 2008 in Iraq, inside surfaces of heavily-used, tactical vehicles (Experimental Group) were sampled with sterile, pre-moistened swabs. Swabs, along with positive and negative controls, were shipped to the reference laboratory in Washington, DC, where they underwent culture, identification and susceptibility testing, and pulsed-field gel electrophoresis. Multidrug-resistant organisms were defined according to the standard Centers for Disease Control and Prevention definitions. High risk organisms (HROs) were defined as susceptible E. coli, A. baumannii, P. aeruginosa, Enterobacter spp, or Klebsiella spp. Concurrently, new counterparts (Control Group) were similarly surveyed in a storage lot in Georgia, USA. Groups were compared using the Chi-squared test.ResultsOne hundred thirty-nine consecutive vehicles including all available ambulances were sampled, yielding 153 swabs. Nineteen were lost or damaged during shipping. Seventy-nine swabs yielded growth of one or more Gram-negative bacteria. The amount and genotype of MDROs in heavily-used vehicles, including those involved in roadside bombings, were compared to control vehicles and to strains isolated from wounds and environmental surfaces at the base hospital. Predominant organisms included P. agglomerans (34%), S. flexneri (8%), E. vulneris (6%), Pseudomonas sp. (6%), and K. pneumonia (6%). No MDROs were isolated. Thirteen vehicles (eight of 94 experimental and five of 45 control) yielded HRO. There was no difference in contamination rates (P = .63). No HROs were isolated from ambulances. No clonal association existed between vehicle and hospital strains.ConclusionGiven the implications that this knowledge gap has on military and civilian prehospital reservoirs of infection, further study is warranted to confirm these findings and identify targets for preventive intervention throughout civilian disaster and military casualty evacuation chains.LeshoE, AkeJ, HuangX, CashDM, NikolichM, BarberM, RobensK, GarnettE, LindlerL, ScottP. Amount of usage and involvement in explosions not associated with increased contamination of prehospital vehicles with multi-drug-resistant organisms. Prehosp Disaster Med. 2013;28(2):1-3..
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Hauser, Elisabeth, Erhard Tietze, Reiner Helmuth, Ernst Junker, Kathrin Blank, Rita Prager, Wolfgang Rabsch, Bernd Appel, Angelika Fruth, and Burkhard Malorny. "Pork Contaminated with Salmonellaenterica Serovar 4,[5],12:i:−, an Emerging Health Risk for Humans." Applied and Environmental Microbiology 76, no. 14 (May 14, 2010): 4601–10. http://dx.doi.org/10.1128/aem.02991-09.
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ABSTRACT Salmonella enterica subsp. enterica serovar 4,[5],12:i:− is a monophasic variant of S. enterica serovar Typhimurium (antigenic formula 4,[5],12:i:1,2). Worldwide, especially in several European countries and the United States, it has been reported among the 10 most frequently isolated serovars in pigs and humans. In the study reported here, 148 strains of the monophasic serovar isolated from pigs, pork, and humans in 2006 and 2007 in Germany were characterized by various phenotypic and genotypic methods. This characterization was done in order to investigate their clonality, the prevalence of identical subtypes in pigs, pork, and humans, and the genetic relatedness to other S. enterica serovar Typhimurium subtypes in respect to the pathogenic and resistance gene repertoire. Two major clonal lineages of the monophasic serovar were detected which can be differentiated by their phage types and pulsed-field gel electrophoresis (PFGE) profiles. Seventy percent of the strains tested belonged to definite phage type DT193, and those strains were mainly assigned to PFGE cluster B. Nineteen percent of the strains were typed to phage type DT120 and of these 86% belonged to PFGE cluster A. Sixty-five percent of the isolates of both lineages carried core multiresistance to ampicillin, streptomycin, tetracycline, and sulfamethoxazole encoded by the genes bla TEM1-like, strA-str B, tet(B), and sul2. No correlation to the source of isolation was observed in either lineage. Microarray analysis of 61 S. enterica serovar 4,[5],12:i:− and 20 S. enterica serovar Typhimurium isolates tested determining the presence or absence of 102 representative pathogenicity genes in Salmonella revealed no differences except minor variations in single strains within and between the serovars, e.g., by presence of the virulence plasmid in four strains. Overall the study indicates that in Germany S. enterica serovar 4,[5],12:i:− strains isolated from pig, pork, and human are highly related, showing their transmission along the food chain. Since the pathogenicity gene repertoire is highly similar to that of S. enterica serovar Typhimurium, it is essential that interventions are introduced at the farm level in order to limit human infection.
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Diaz, Heidi Torres, Ruth Serrano, Jason E. Bowling, Gregory Anstead, and Heta Javeri. "802. Use of N-Acetylcysteine for Prevention and Treatment of Isoniazid Induced Liver Injury During Treatment of Mycobacterial Infections." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S287—S288. http://dx.doi.org/10.1093/ofid/ofy210.809.
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Abstract Background Hepatotoxicity secondary to therapy for Mycobacterium tuberculosis (MTB) is a common complication that may lead to treatment interruption. N-Acetylcysteine (NAC) exerts a hepatoprotective effect by repleting glutathione stores and enhancing the cellular antioxidant defense mechanism. NAC has been found to be protective against liver toxicity in animals treated for MTB infection. Randomized controlled trials have shown that its use in humans also decreases the risk of hepatotoxicity associated with anti-MTB treatment but there is minimal data regarding its utility for treatment of liver toxicity. Methods Patients who received NAC from January 2012 to March 2018 for prophylaxis and treatment of increasing liver function tests (LFTs) while on isoniazid (INH) were included. A retrospective review of the medical record system was performed. Results Nineteen patients were included. Eight received NAC for treatment. The average age was 49 years. Seventy percent of patients were male. The mean BMI was 25. Five patients had underlying liver cirrhosis and two had hepatic steatosis. Eleven patients had Hepatitis C (HCV) and one had active Hepatitis B infection. Ten patients had MTB pulmonary infection, thee had latent TB infection, two meningitis, and three had disseminated disease. One patient was treated for atypical mycobacterial infection. The dose of NAC used was 600 mg oral twice daily and the duration was variable. The prophylaxis group had stable LFTs during treatment, except for two patients whose enzymes increased more than three times the upper limit of normal. These two patients had underlying HCV and liver cirrhosis. Only one required discontinuation of INH. This group received NAC for an average of 47 days. The treatment group had a favorable trend of liver enzymes after NAC initiation, with levels significantly improving by day 14 (Figures 1 and 2). Three patients did not require discontinuation of antibiotics. INH was stopped prior to NAC initiation in four patients. No side effects of NAC were documented in any patient. Conclusion NAC is a safe and effective measure to prevent and treat hepatotoxicity secondary to INH therapy. More studies are needed to determine its optimal dose and duration for this indication. Disclosures All authors: No reported disclosures.
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Gerszten, Peter C., Steven A. Burton, Cihat Ozhasoglu, Kevin J. McCue, and Annette E. Quinn. "RADIOSURGERY FOR BENIGN INTRADURAL SPINAL TUMORS." Neurosurgery 62, no. 4 (April 1, 2008): 887–96. http://dx.doi.org/10.1227/01.neu.0000318174.28461.fc.
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Abstract OBJECTIVE The role of stereotactic radiosurgery for the treatment of intracranial benign tumors is well established. There is less experience and more controversy regarding its use for benign tumors of the spine. This study evaluated the clinical efficacy of radiosurgery as part of the treatment paradigm of selected benign tumors of the spine. METHODS Seventy-three benign intradural extramedullary spinal tumors were treated with a radiosurgery technique and prospectively evaluated. Patient ages ranged from 18 to 85 years (mean age, 44 yr); the follow-up period was 8 to 71 months (median, 37 mo). Lesion location included 43 cervical, five thoracic, 19 lumbar, and six sacral. Tumor histology included neurofibroma (25 cases), schwannoma (35 cases), and meningioma (13 cases). Twenty-one cases were associated with neurofibromatosis Type 1, and nine patients had neurofibromatosis Type 2. Nineteen tumors (26%) had previously undergone open surgical resection, and six tumors (8%) had previously been treated with conventional external beam irradiation techniques. RESULTS Similar radiation doses were prescribed for all three histopathologies. The maximum intratumoral dose was 1500 to 2500 cGy (mean, 2164 Gy). Tumor volume ranged from 0.3 to 93.4 cm3 (mean, 10.5 cm3; median, 4.11 cm3). Radiosurgery was used for the treatment of postsurgical radiographic progression in 18 cases; it was used as the primary treatment modality in 14 cases; it was used for treatment of radiographic tumor progression in nine cases; and it was used for the treatment of postsurgical residual tumor in two cases. Long-term pain improvement occurred in 22 out of 30 cases (73%). Long-term radiographic tumor control was demonstrated in all cases. Three patients experienced new symptoms attributed to radiation-induced spinal cord toxicity 5 to 13 months after treatment. CONCLUSION Single fraction radiosurgery was found to be clinically effective for the treatment of benign extramedullary spinal neoplasms. Although surgical extirpation remains the primary treatment option for most benign spinal tumors, radiosurgery was demonstrated to have short-term clinical benefits for the treatment of such lesions. The long-term efficacy of spinal radiosurgery for such tumors will be determined with longer follow-up periods. Its role in patients with neurofibromatosis will also be further defined with greater clinical experience.
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Risavi, Brian L., K. J. Sabotchick, and Christopher J. Heile. "Portable Suction Unit Failure in a Rural EMS System." Prehospital and Disaster Medicine 28, no. 4 (April 18, 2013): 388–90. http://dx.doi.org/10.1017/s1049023x13000393.
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AbstractIntroductionPortable suction units used by EMS personnel are utilized infrequently and often are powered by batteries. Lack of use and inspection often results in failure of the device when it is needed. The purpose of this study was to examine the incidence of portable suction unit failure in a rural EMS system and to identify the reasons for failures.MethodsA convenience sample was obtained through both random inspections by the staff of a regional EMS council and data from twice monthly checks reported by respective EMS agencies following a standard protocol for each unit. A standard protocol was used, including checking the vacuum level on each suction unit and inspecting the tubing, canister, and battery. Each inspector assessed whether the unit was capable of achieving 300 mmHg of suction within four seconds. Also, the unit was inspected for any signs of misalignment or dry rot of the gasket, kinking of suction hose, damage to the suction canister, weak/dead battery, or defective pump. Findings were recorded.ResultsOver a two-year period, 9,631 suction unit inspections were completed. There were 233 failures (2.4%) noted. The majority (126, 54.1%) were due to battery failure. Seventy-three units failed due to other reasons (not recorded, switch failure, battery not seated). Ten inspections failed due to incorrect assembly. Nineteen inspections failed due to defects with the suction canister. Five inspections failed due to kinked/disconnected suction tubing.ConclusionOnly a relatively small percentage of inspections of suction units revealed failures (4.6% Advanced Life Support, 8.6% Basic Life Support) using the above-stated criteria. However, given the importance of airway management and potential complications associated with airway compromise, including aspiration pneumonia, hypoxia, and hemodynamic instability, this is of concern relative to the morbidity and mortality that could be related to airway failure. Due to the relative infrequency of use and the nature of portable suction units, the potential for lack of maintenance and deficiencies in routine inspection may impact the functional status of these devices in EMS agencies. Clearly, improved documentation of battery installation date, charging in accordance with manufacturer recommendations, and thorough inspection of the portable suction unit in its entirety will ensure readiness of these devices. Additionally, more rigorous documentation and analysis of inspections should be a focus of EMS agencies.RisaviBL,SabotchickKJ,HeileCJ.Portable suction unit failure in a rural EMS system.Prehosp Disaster Med.2013;28(4):1-3.
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Liu, Terrence, Donglu Xie, Beverley Adams-Huet, Jade Le, Christina Yek, Dipti Ranganathan, Robert W. Haley, David Greenberg, and Ricardo La Hoz. "Solid Organ Transplantation (SOT) and Data Mining: Bloodstream Infections (BSI) Have a Significant Impact on One-Year Survival, and qSOFA ≥ 2 Predicts 30-Day Mortality." Open Forum Infectious Diseases 4, suppl_1 (2017): S10. http://dx.doi.org/10.1093/ofid/ofx162.025.
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Abstract Background We created a retrospective and prospective database of SOT recipients using innovative data mining tools. This study describing the epidemiology of BSI in SOT serves as a proof of concept of such techniques in clinical research. Methods The design of the study was a retrospective, single-center, cohort study. Data mining tools were used to extract information from the electronic medical record and merged it with data from the SRTR (Figure 1). First SOT from January 1, 2010 to December 31, 2015 were included. Charts of subjects with positive blood cultures were manually reviewed and adjudicated using CDC/NHSN and SCCM/ESICM criteria. The 1-year cumulative incidence was calculated using the Kaplan–Meier method. Cox proportional hazards models were used to identify risk factors for BSI and 1-year mortality. BSI was analyzed as a time-dependent covariate in the mortality model. Fisher’s exact test and chi-square were used to identify risk factors for 30-day mortality and MDRO. Results A total of 917 SOT recipients met inclusion criteria. Seventy-five patients experienced at least one BSI. The cumulative incidence was 8.4% (95% CI 6.8–10.4) (Figure 2). The onset of the first BSI episode was: 30 episodes (40%) <1 month, 33 (44%) 1–6 months, and 12 (16%) >6 months. The most common pathogens were Klebsiella sp. (16%), Vancomycin-resistant E. faecium (12%), E. coli (12%), CoNS (12%), and Candida sp. (9.3%). Nineteen isolates (25%) were identified as MDRO; the risk of MDRO was highest <1 month compared with 1–6 and >6 months (44.8 vs. 12.1 vs. 16.7; P = 0.01). The most common source of BSI was CLABSI (29%) (Figure 3). In multivariable analysis, the risk of BSI was associated with organ type (HR [95% CI] = Multiorgan 3.5 [1.1–11.6], liver 2.5 [1.1–5.4], heart 2.4 [1.1–5.1]) and acquisition of a BSI was associated with a higher 1-year mortality (HR = 8.7 [5.1–14.7]). In univariable analysis, a polymicrobial BSI (14.7 vs. 57.1%; P = 0.02), qSOFA ≥ 2 (0.0 vs. 25.5%; P = 0.02) and septic shock (3.9 vs. 52.2%; P < 0.001) were associated with an increased risk of death at 30 days. Conclusion A BSI significantly affects the 1-year survival of SOT recipients. A qSOFA ≥ 2 can be used to identify patients at risk for death. Additionally, this study illustrates the potential of data mining tools to study infectious complications. Disclosures All authors: No reported disclosures.
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Gul, Zartash, Stephan Anderson, Stacey Slone, Saurabh Chhabra, Gregory Monohan, Dianna Howard, Amber Lawson, and John Hayslip. "Is Rituximab Needed With High Dose Chemotherapy and Autologous Stem Cell Transplant When Patients With Non-Hodgkin’s Lymphoma Have Been Exposed To It?" Blood 122, no. 21 (November 15, 2013): 5552. http://dx.doi.org/10.1182/blood.v122.21.5552.5552.
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Abstract Introduction The value of Rituximab with High dose chemotherapy and autologous stem cell transplant (auto-HCT) has been evaluated in some retrospective studies. It is noted that the addition Rituximab to auto-HCT results in significant improvement in overall (OS) and disease free survival (DFS). However, it is unclear that the addition of Rituximab with auto-HCT would result in significant benefit in patients who have received prior Rituximab based therapy. Methods We retrospectively evaluated twenty seven consecutive patients who had B cell non-Hodgkin's lymphoma (NHL) and underwent auto- HCT at Markey cancer center between January 2010 and December 2012. All patients received 375 mg/m2of Rituximab with chemotherapy. Rituximab was not administered with high dose chemotherapy (BEAM: BCNU, Etoposide, Cytarabine and Melphalan) prior to auto-HCT. All patients received GCSF starting day 5 after auto-HCT. Results There were 27 patients who underwent auto-HCT for NHL. Median age of the patients was 60 years (36-72 years). Nineteen patients were male and 8 patients were female. Fifteen patients were in complete remission (CR) and the rest were in partial remission (PR). Patients had: Diffuse large B cell lymphoma (DLBCL=11 patients): Mantle cell lymphoma (MCL=13 patients): follicular lymphoma (3 patients). Median CD 34 count of infused cells was 4.14 x 106 cell/kg (2.26- 9.45). Median time to neutrophil recovery was 11 days (9-14). Median lymphocyte count at day 30 after auto HCT was 1130 x 10 6/l (320- 5180). After a median follow up of 7.9 months (3.0- 32.4) eight patients had relapsed. Five patients who had relapsed had refractory disease before auto-HCT. Non -Relapse mortality (NRM) is shown in figure 1. Median overall survival and disease free survival were not reached. Seventy percent patients had not relapsed. We did not find any factors associated with relapse. Conclusion We performed a retrospective study to evaluate the impact of Rituximab with high dose chemotherapy and in patients with NHL. Review of literature showed that median 2 year and 5 year OS was 80% and 69% in patients who received Rituximab with auto HCT. Median 2 year DFS was 67%. In our study 70% patients were relapse free at a median follow up of 8 months. We would need a longer follow up to determine the efficacy of Rituximab with auto- HCT in patients with NHL who had prior exposure to Rituximab. Disclosures: Off Label Use: The use of Thymoglobulin® for GVHD prevention. Hayslip:Sanofi: Research Funding; Janssen: Research Funding; Pfizer: Research Funding; Celgene: Research Funding.
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Iglebekk, Wenche, Carsten Tjell, and Peter Borenstein. "Pain and other symptoms in patients with chronic benign paroxysmal positional vertigo (BPPV)." Scandinavian Journal of Pain 4, no. 4 (October 1, 2013): 233–40. http://dx.doi.org/10.1016/j.sjpain.2013.06.004.
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AbstractBackground and aimA diagnosis of chronic benign paroxysmal positional vertigo (BPPV) is based on brief attacks of rotatory vertigo and concomitant nystagmus elicited by rapid changes in head position relative to gravity. However, the clinical course of BPPV may vary considerably from a self-limiting to a persisting and/or recurrent disabling problem. The authors’ experience is that the most common complaints of patients with chronic BPPV are nautical vertigo or dizziness with other symptoms including neck pain, headache, widespread musculoskeletal pain, fatigue, and visual disturbances. Trauma is believed to be the major cause of BPPV in individuals younger than fifty years. Chronic BPPV is associated with high morbidity. Since these patients often suffer from pain and do not have rotatory vertigo, their symptoms are often attributed to other conditions. The aim of this study was to investigate possible associations between these symptoms and chronic BPPV.MethodsDuring 2010 a consecutive prospective cohort observational study was performed. Diagnostic criteria: (A) BPPV diagnosis confirmed by the following: (1) a specific history of vertigo/dizziness evoked by acceleration/deceleration, (2) nystagmus in the first position of otolith repositioning maneuvers, and (3) appearing and disappearing nystagmus during the repositioning maneuvers; (B) the disorder has persisted for at least six months. (C) Normal MRI of the cerebrum. Exclusion criteria: (A) Any disorder of the central nervous system (CNS), (B) migraine, (C) active Ménière’s disease, and (D) severe eye disorders. Symptom questionnaire (‘yes or no’ answers during a personal interview) and Dizziness Handicap Inventory (DHI) were used.ResultsWe included 69 patients (20 males and 49 females) with a median age of 45 years (range 21-68 years). The median duration of the disease was five years and three months. The video-oculography confirmed BPPV in more than one semicircular canal in all patients. In 15% there was a latency of more than 1 min before nystagmus occurred. The Dizziness Handicap Inventory (DHI) median score was 55.5 (score >60 indicates a risk of fall). Seventy-five percent were on 50-100% sick leave. Eighty-one percent had a history of head or neck trauma. Nineteen percent could not recall any history of trauma. In our cohort, nautical vertigo and dizziness (81%) was far more common than rotatory vertigo (20%). The majority of patients (87%) reported pain as a major symptom: neck pain (87%), headache (75%) and widespread pain (40%). Fatigue (85%), visual disturbances (84%), and decreased concentration ability (81%) were the most frequently reported symptoms. In addition, unexpected findings such as involuntary movements of the extremities, face, neck or torso were found during otolith repositioning maneuvers (12%). We describe one case, as an example, how treatment of his BPPV also resolved his chronic, severe pain condition.ConclusionThis observational study demonstrates a likely connection between chronic BPPV and the following symptoms: nautical vertigo/dizziness, neck pain, headache, widespread pain, fatigue, visual disturbances, cognitive dysfunctions, nausea, and tinnitus.ImplicationsPatients with complex pain conditions associated with nautical vertigo and dizziness should be evaluated with the Dizziness Handicap Inventory (DHI)-questionnaire which can identify treatable balance disorders in patients with chronic musculoskeletal pain.
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Bavinzski, Gerhard, Monika Killer, Andreas Gruber, Andrea Reinprecht, Cordell E. Gross, and Bernd Richling. "Treatment of basilar artery bifurcation aneurysms by using Guglielmi detachable coils: a 6-year experience." Journal of Neurosurgery 90, no. 5 (May 1999): 843–52. http://dx.doi.org/10.3171/jns.1999.90.5.0843.
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Object. The authors retrospectively analyzed the results of their 6-year experience in the treatment of basilar artery (BA) bifurcation aneurysms by using Guglielmi detachable coils (GDCs).Methods. This analysis involved 45 BA tip aneurysms in 16 men and 29 women who ranged in age from 23 to 78 years (mean 50 years). Seventy-five percent of the aneurysms had ruptured and 25% remained unruptured. Of the group whose aneurysms hemorrhaged, 14 patients were Hunt and Hess Grade I or II and 20 were Hunt and Hess Grades III to V; 32 patients were treated within 2 weeks of their subarachnoid hemorrhage (SAH). Initially, treatment with GDCs was limited to poor-grade high-risk patients who refused surgery or patients in whom surgery proved unsuccessful. Later in the study, good-grade patients with narrow-necked aneurysms were also treated using GDCs.The length of clinical follow up ranged from 1 to 72 months (average 27.4 months) in the 37 surviving patients. In 33 of the 45 aneurysms treated with coil placement, good to excellent results were achieved. There were 12 poor results (27%) including one in a patient from the non-SAH group who suffered a thrombotic complication due to an underlying vasculitis. Eight deaths were recorded in this group of 45 patients. One of these deaths was caused by a complication related to anesthesia, one by unknown causes, and six resulted from complications of the disease. One patient rebled on the 2nd day after the endovascular procedure. The mortality and permanent morbidity rates directly related to the intervention were 2.2% and 4.4%, respectively.Angiographic studies obtained immediately postintervention demonstrated 99 to 100% occlusion in 30 (67%) of the aneurysms; nine (20%) were more than 90% occluded; and six (13%) were less than 90% occluded by the GDCs. Follow-up angiograms were obtained in 31 patients between 2 and 72 months after coil placement. Nineteen (61%) of the follow-up angiograms revealed stable results (that is, no change from initial treatment). Twelve of the 31 showed coil compaction, but only eight of these lesions could accept additional coils.In large aneurysms recanalization was seen in 57%, and some of the larger lesions required as many as four embolizations (mean 1.7) to achieve optimal occlusion. When small-necked aneurysms were analyzed as a subset, a stable angiographic result was seen in 92%.Conclusions. Use of GDCs led to excellent clinical and angiographic results in the majority of patients with BA tip aneurysms included in this limited follow-up study. Rebleeding was encountered in one of the 34 previously ruptured BA aneurysms treated with GDCs, and no hemorrhages have been documented in the 11 unruptured aneurysms treated with GDCs in this series. Long-term follow-up studies are necessary before it is possible to compare adequately the treatment of aneurysms with coil placement to the gold standard of aneurysm clipping.
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Linden, Erica, Steven L. McAfee, Bimalangshu R. Dey, Karen Ballen, Susan Saidman, Christine Colby, Megan Sykes, and Thomas R. Spitzer. "Outcomes of Patients with Engraftment Syndrome (ES) Following Nonmyeloablative Hematopoietic Stem Cell Transplant (SCT) for Hematologic Malignancy(HM)." Blood 106, no. 11 (November 16, 2005): 3661. http://dx.doi.org/10.1182/blood.v106.11.3661.3661.
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Abstract ES may accompany hematologic recovery following SCT and is characterized by fever and rash, in addition to one of the following clinical syndromes: noncardiogenic pulmonary edema, hepatic dysfunction, renal dysfunction, weight gain, or transient encephalopathy. A retrospective analysis was performed to evaluate the incidence of ES using a published clinical definition (Spitzer TR, Bone Marrow Transplant2001; 27:893–898), the use of corticosteroids in the peri-engraftment period, the relationship of ES to the development of GVHD, and the fate of the patient’s chimerism. Seventy-three patients with a HM (NHL, n=45; HD, n=9; AML, n=6; ALL, n=1; CLL, n=6; MDS, n=1; MM, n=4) who were treated with a nonmyeloablative conditioning regimen consisting of cyclophosphamide, antithymocyte globulin, thymic irradiation, cyclosporine, and hematopoietic SCT (bone marrow, n =57; peripheral blood stem cells, n =15) were analyzed. Chimerism was assessed weekly for the first 100 days, then q6 months by VNTR/STR analysis and/or flow cytometry. In the absence of full donor chimerism (FDC) or evidence of acute GVHD, donor leukocyte infusions (DLI) were given beginning 5 weeks post-transplant to convert mixed chimerism (MC) to FDC and thus maximize a graft-versus-tumor effect. Thirty-five (50%) patients met the clinical definition of ES, presenting with fever and rash (100% of ES patients), hepatic dysfunction (74.3%), fluid retention/weight gain (60%), noncardiogenic pulmonary edema (22.9%), renal dysfunction (22.9%), and transient encephalopathy (5.7%). Three (4.1%) patients never engrafted and thus were censored from the population. Median time to engraftment was 13 (range 9 to 18) days in ES patients and 14 (range 9 to 21) days in non-ES patients. The incidence of significant (≥ grade II) aGVHD was 45.7% in ES patients versus 22.9% in non-ES patients. The incidence of chronic GVHD was similar in both groups (63.6% in ES patients vs. 68.0% in non-ES patients). Loss of donor chimerism (LDC) was seen at a lower rate in ES patients (15.2%) vs. non-ES patients (36.4%). Conversely, full donor chimerism (FDC) was higher in ES patients (48.5%) versus non-ES patients (36.4%). Corticosteroids were administered based on clinical suspicion of ES. Thirty two (91.4%) of ES patients and nineteen (54.3%) of non-ES patients received steroids. Resolution of clinical abnormalities occurred in twenty seven (84.4%) of ES patients and eighteen (94.7%) of patients who did not fulfill the criteria for ES. In conclusion, patients with ES had a higher propensity to develop clinically significant acute GVHD, suggesting that ES may represent early GVHD. However, those who developed LDC and ES had indistinguishable clinical presentations of their ES. Thus, ES represents heterogeneous populations of patients with diverse immunologic alloreactivity (either GVH or HVG reactivity). The high incidence of ES (and of both GVHD and LDC) in this population of patients suggests that competing GVH and HVG alloreactivity following nonmyeloablative conditioning (and in all likelihood the occurrence of a “cytokine storm”) might be responsible for the clinical manifestations of this syndrome.
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Quintás-Cardama, Alfonso, Hagop M. Kantarjian, Rajyalakshmi Luthra, Susan o'Brien, Elias Jabbour, Gautam Borthakur, Farhad Ravandi, et al. "Efficacy of Frontline Nilotinib Therapy in Patients (Pts) with Newly Diagnosed Philadelphia Chromosome (Ph)-Positive Chronic Myeloid Leukemia in Early Chronic Phase (CML-CP)." Blood 118, no. 21 (November 18, 2011): 454. http://dx.doi.org/10.1182/blood.v118.21.454.454.
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Abstract Abstract 454 Efficacy of Frontline Nilotinib Therapy in Patients (Pts) with Newly Diagnosed Philadelphia Chromosome (Ph)-Positive Chronic Myeloid Leukemia in Early Chronic Phase (CML-CP) Alfonso Quintás-Cardama, Hagop Kantarjian, Raja Luthra, Susan O'Brien, Elias Jabbour, Gautam Borthakur, Farhad Ravandi, Guillermo Garcia-Manero, Stefan Faderl, Marina Konopleva, William Wierda, Elizabeth Burton, Jorge Cortes 1MD Anderson Cancer Center, University of Texas, Houston, TX Background: In 2005, we initiated a phase II study of nilotinib as 1st line therapy in pts with newly diagnosed CML-CP to investigate the efficacy and safety of nilotinib as frontline therapy for pts with CML-CP. Methods: The primary objective was to estimate the proportion of pts attaining major molecular response (MMR) at 12 months (mo). Pts with untreated CML-CP within 6 mo from diagnosis were eligible and received nilotinib 400 mg twice daily. Results: 100 pts (41% female) have received for a median of 24 mo (range 1 to 72mos). Median age was 49 years (range 17–86). Median WBC, PB blasts, PB basophils, hemoglobin, and platelet count was 42.6, 0%, 2.5%, 12.3, 307, respectively. Five pts (5%) had a variant Philadelphia chromosome and 1 (1%) had deletion of derivative chromosome 9. Seventy-two (72%), 20 (20%), and 8 (8%) pts had low, intermediate, and high Sokal risk score. Among the 102 CP pts who were not in CHR at the start, 100 (98%) achieved CHR (one discontinued after 2 weeks without adverse events). Among 73 CP pts followed for at least 12 mo, 69 (95%) achieved a complete cytogenetic response (CCyR). MMR at 18 mo has been achieved in 51 (89%) pts, including 30 (52%) with a complete molecular response (CMR)(Table 1). The median time to achieve CCyR, MMR was 6 mo each. Grade 3–4 thrombocytopenia, neutropenia, and anemia occurred in 9%, 12%, and 6% pts. The most frequent non-hematologic toxicities were rash (62%), pain (57%), and elevated transaminases (45%) and bilirubin (42%). However, grade 3–4 non-hematologic adverse events (possible, probable or suspected relationship only) were rare, including: pain and increased bilirubin (4% each), elevated lipase, fatigue, and elevated transaminases (2% each), and hyperglycemia (1%). One (1%) pt experienced QTc prolongation (grade 2; QTc prolonged from 444msec to 483msec), not associated with arrhythmias and resolved after a brief treatment interruption. Forty-five (45%) pts had transient treatment interruptions (median days off-nilotinib 7 [range 1–68]) and 27 (27%) had dose reductions. Of the patients that were dose reduced, their current or last known dose was either 200mg daily (n=7), 200mg twice daily (n=14), or 400mg daily (n=6). Nineteen (19%) pts terminated nilotinib therapy due to toxicity (n=7), personal reasons or loss to follow-up (n=7), loss of MCyR (n=2), progression to BP (n=2), or death (n=1). Of the pts who discontinued therapy, 3 were tested for BCR-ABL1 mutations; 2 were found to have mutations (F359C and Y253H). The 48 mo probability of EFS (event= loss of CHR, loss of MCyR, AP/BP, or death) is 88%. The annual rate of events during the first 48 mo of follow-up was 4%, 0%, 2%, 5%, and 0% and the rate of transformation 2%, 0%, 0%, and 0%, respectively. The best response achieved on nilotinib by the 2 pts that transformed to BP was CCyR and PCyR, respectively. The overall survival at 48 mos is 96%. One pt died due to stroke, unrelated to nilotinib. No other vascular events have been observed to date. Conclusion: Nilotinib 400 mg twice daily induces CCyR in 78% of pts as early as 3 mo and MMR in 86% at 12 mo after the start of therapy, with very low rates of progression to AP/BP and a mild toxicity profile. Disclosures: No relevant conflicts of interest to declare.
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Tiippana, Elina, Katri Hamunen, Tarja Heiskanen, Teija Nieminen, Eija Kalso, and Vesa K. Kontinen. "New approach for treatment of prolonged postoperative pain: APS Out-Patient Clinic." Scandinavian Journal of Pain 12, no. 1 (July 1, 2016): 19–24. http://dx.doi.org/10.1016/j.sjpain.2016.02.008.
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AbstractBackground and aimsPersistent postoperative pain (PPP) is a significant clinical problem. Several patient-related risk factors for PPP have been identified, including a previous chronic pain problem, young age, female gender and psychological vulnerability. Intra- and postoperative risk factors include surgical complications such as infections, haematoma, nerve damage and repeated surgery. As the length of hospital stay has been shortened, some patients may be discharged despite ongoing pain and insufficient analgesic medication. The challenge is to identify patients at high risk of developing PPP and to create a targeted care pathway to ensure effective and safe pain treatment especially in the subacute postoperative phase at home. This observational study describes the first two years of the Acute Pain Service Out-Patient Clinic (APS-OPC) at the Helsinki University Hospital.MethodsPatient characteristics, known risk factors, and details of treatment of PPP for the first 200 patients referred to our APS-OPC were retrospectively collected from the medical records. The APS-OPC clinic functions in close collaboration with the Multidisciplinary Pain Clinic (MPC), and the number of patients in need of physiotherapist, psychologist or psychiatrist counselling was recorded, as well as the number of patients referred to the MPC for further PPP management.ResultsPatients were referred to the APS-OPC from different surgical specialities, the two most common being thoracic and orthopaedic surgery. Seventy per cent of the patients (139/200) presented symptoms indicating neuropathic postsurgical pain. The patients had, on average, five risk factors for PPP. The median time from surgery to the first contact to the APS-OPC was two months, and the median duration of follow-up was 2.8 months (0–16 months). The median number of contacts with APS-OPC was 3 (range 1–14). Every fourth patient needed only one contact to the APS-OPC. Nineteen per cent of the patients had an appointment with the physiotherapist and 20% with a psychologist or psychiatrist. At discharge after surgery, 54% of the patients were using weak opioids, 32% strong opioids and 71% gabapentinoids; at discharge from the APS-OPC, these numbers were 20%, 6% and 43%, respectively. Twenty-two per cent of the patients were referred to the MPC for further pain management.ConclusionsThe APS-OPC provides a fluent fast-track method of ensuring effective multimodal analgesia in the subacute recovery phase after surgery. Even strong opioids can be safely used after discharge and then tapered off in close supervision of the APS-OPC anaesthesiologist. As the APS-OPC was implemented in close collaboration with the MPC, the multidisciplinary resources are easily available during the course of the APS-OPC treatment.ImplicationsThe first two years of the APS-OPC have shown that a significant number of surgical patients benefit from continuing active pain management after discharge from hospital. This fast-track service provides physician-supervised titration of analgesics to improve pain relief in the subacute phase. An important task of the APS-OPC is to ensure that strong opioids are not inappropriately continued after recovery. Another goal of the APS-OPC is to identify patients in need of multidisciplinary pain management services to prevent chronification.
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Marcotte, Nathalie, Marie-Claude Michel, Louise Deschenes, Nathalie Letarte, Daniel Froment, Emilie Lemieux-Blanchard, France Varin, et al. "Descriptive Analysis of Bortezomib Use in Multiple Myeloma in Four Adult University Teaching Hospitals in Quebec, Canada." Blood 126, no. 23 (December 3, 2015): 5573. http://dx.doi.org/10.1182/blood.v126.23.5573.5573.
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Abstract Background: Bortezomib, a reversible inhibitor of the 26S proteasome widely used in the treatment of multiple myeloma, is now being used in various other indications. Pharmacy directors gave the Therapeutic Drug Management Program (TDMP - www.pgtm.qc.ca) the mandate to evaluate bortezomib use in four University Hospitals in Quebec, Canada. Objectives: Describe bortezomib use for all indications in our hospitals and review its utilisation in the treatment of multiple myeloma. Methods: A review of pharmacy databases was performed to identify patients who received bortezomib between June1st 2012 and May 31st 2013. The pharmaceutical and medical records of every patient who received bortezomib were reviewed to assess the treatment, pathology and adverse events. Results: Two hundred and thirty two bortezomib regimens were administered to 227 different patients during the study period. Median age was 68. The most frequent indication (55%) was first-line treatment of multiple myeloma (n=128) followed by treatment of relapsed/refractory disease (31%) (n=73). Various other indications, including amyloidosis (n=17), lymphoplasmacytic lymphoma (n=12) and mantle cell lymphoma (n=2), represented 13% of the population. At the time of data analysis, 35% of patients were still treated with bortezomib, 25% had finished their planned treatment and 34% had discontinued treatment because of adverse events or disease progression. Fifteen patients (6%) died during the study period. Among the 45 patients eligible for autologous stem cell transplant (ASCT), the main regimen used was the association of bortezomib and dexamethasone (VelDex) (n=27), primarily using subcutaneous bortezomib (n=24) at 1.3 mg/m2 (n=30). Median treatment duration was four cycles. Twenty-eight patients have undergone ASCT and only two progressed. The association of bortezomib, melphalan and prednisone (VMP) (54.2%) followed by VelDex (29%) and the association of cyclophosphamide, bortezomib and dexamethasone (CyborD) (16.8%) were the regimens used in the population (n=83) not eligible to ASCT. Response rate using international uniform response criteria for multiple myeloma was 47.9% excluding patients still receiving treatment at the time of data collection. Seventy three patients received bortezomib for relapsed/refractory myeloma. Of these patients, thirty two (43.8%) discontinued therapy, nineteen due to disease progression, eight for the occurrence of side effects and five for other reasons. The initial dose was variable, from 1.0 to 1.6 mg/m2, and close to half of this patient population received CYBorD (49.4%), followed by VelDex (30.2%) and VMP protocols (15%). The number of cycles for patients who completed treatment (4 to 9) as well as the median exposure time (57 to 223 days) was also highly variable. Respectively 8.5% and 10.9% of the population treated with bortezomib for multiple myeloma were hospitalized (n=17) or had to discontinue treatment (n=22) because of adverse events (mostly hematologic toxicity, peripheral neuropathy or gastro-intestinal toxicity). Conclusions: Bortezomib is widely used in the treatment of multiple myeloma. Treatment algorithms should be developed and implemented to optimize the use of bortezomib, particularly in the relapsed/refractory setting. Standard regimens should also be implemented in each center. The utilisation of pre-printed orders for the prescription of chemotherapy regimens promotes uniform prescription. A review of the literature should be performed and recommendations should be made for the use of bortezomib in off-label indications like amyloidosis and lymphoplasmacytic lymphoma. Disclosures Off Label Use: bortezomib use in amyloidosis and lymphoplasmacitic lymphoma. Lemieux-Blanchard:celgene: Membership on an entity's Board of Directors or advisory committees; Amgen and Janssen: Other: preceptorship. Bérard:Janssen: Honoraria. Sebag:Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Novartis: Honoraria.
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Rolston, Kenneth V. I., Scott A. McConnell, Jack Brown, and Kenneth C. Lamp. "Daptomycin Use in Cancer Patients with Neutropenia." Blood 110, no. 11 (November 16, 2007): 2289. http://dx.doi.org/10.1182/blood.v110.11.2289.2289.
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Abstract Infections occurring during neutropenia in cancer patients (pts) frequently involve Gram-positive pathogens and are complicated by antibiotic resistance. Outcomes for infections due to either methicillin-resistant or -susceptible Staphylococcus aureus (MRSA, MSSA) treated with vancomycin are considered suboptimal by many clinicians (Sakoulas G. J Clin Microbiol2004;42:2398–402). New effective agents are needed for treatment. Data were collected retrospectively as part of an ongoing registry (Cubicin Outcomes Registry and Experience; CORE, 2005 and 2006 program years). Data were collected on demographic and microbiologic characteristics; prior, concomitant and follow-up antibiotics; DAP regimen; and clinical data. Outcomes were assessed at the end of DAP therapy by the investigator who, in most cases, was the infectious disease physician involved in the treatment of the patient. The definitions for clinical outcome were: Cure - clinical signs and symptoms resolved (and/or) no additional antibiotic therapy necessary (or) negative culture reported at the end of therapy; Improved - partial resolution of clinical signs and symptoms (and/or) additional antibiotic therapy warranted at the end of therapy; Failure - inadequate response to therapy: worsening or new/recurrent signs and symptoms (or) need for a change in antibiotic therapy (or) positive culture reported at the end of therapy. Pts reported with neutropenia during DAP, a history of cancer, and evaluable for outcome (cure, improved, failure) were analyzed. Eighty-four pts had a history of cancer and had neutropenia during DAP treatment, of these, 72 (86%) were evaluable for DAP outcome. Sixty-five of 72 (90%) pts had either cure (n=40, 56%) or improved (n=25, 35%) as an outcome. Success rates (cure plus improved) stratified by the lowest WBC during DAP were; 29/34 (85%) for < 100 cells/m3, 26/28 (93%) for 100–499 cells/m3, and 10/10 (100%) for 500–1000 cells/m3, P=0.32. The median (range) time to clinical response in those successfully treated (data reported in 47 pts) was 4 days (1–21). Fifty-nine of 72 (82%) had a hematological malignancy. Fifty-eight percent were male, 22% were ≥66 yrs old, 7% had an initial CrCl <30 mL/min, 18% received DAP in an ICU. Eighty-eight percent of pts received antibiotics before DAP, most frequently with vancomycin (83%), cefepime (17%), and linezolid (16%). The most frequent reason for switching to DAP was prior clinical failure / resistance (54%). The major infections being treated with DAP were bacteremia (76%), UTI / pyelonephritis (10%), and uncomplicated skin and skin structure (6%). Seventy-four percent of pts with a WBC < 100 cells/m3 had a bacteremia. The most common Gram-positive pathogens reported were vancomycin-resistant enterococci (52%), coagulase-negative staphylococci (21%), and S. aureus (14%; 7/11, 64% were MRSA). The median (range) initial DAP dose was 6.0 mg/kg (3–7). The median (range) DAP duration of therapy was 13 days (1–86). Nineteen percent of the pts received DAP as an outpatient at some time during their therapy. There were 37 adverse events (AE) reported in 20 (28%) pts; however, only three AEs in 3 pts (4%) were assessed as possibly related to DAP. The data from the registry provide useful information about the clinical characteristics of neutropenic cancer patients treated with DAP for primarily bacteremia. Most of the pts were bacteremic and there was no difference in outcome regardless of the degree of neutropenia. These data require confirmation via prospective clinical trials.
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Brady, Anna, Sarah Gibson, Lisa Rybicki, Eric Hsi, Edward Copelan, Matt Kalaycio, Mikkael A. Sekeres, et al. "Expression of Phosphorylated Signal Transducer and Activator of Transcription 5 (pSTAT5) Is Associated with An Increased Risk of Death In Acute Myeloid Leukemia." Blood 116, no. 21 (November 19, 2010): 1675. http://dx.doi.org/10.1182/blood.v116.21.1675.1675.
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Abstract Abstract 1675 Background: Acute myeloid leukemia (AML) is characterized by rapid growth, resistance to therapy, and poor overall survival. Clinical and biologic prognostic markers can help define pathogenesis, guide treatment, and identify novel therapies. Phosphorylated signal transducer and activator of transcription 5 (pSTAT5) is one such potential marker. The transcription factor STAT5 regulates many aspects of cell growth, survival, and differentiation. Constitutive activation of STAT5 (by phosphorylation) has been identified in a number of malignancies, including AML. We investigated whether the level of pSTAT5 expression correlates with complete remission (CR) rates, progression-free survival (PFS), and overall survival (OS) in patients (pts) with newly diagnosed AML. Methods: From 1999 to 2005, all adult pts with newly diagnosed AML (WHO criteria) receiving induction chemotherapy and with an available diagnostic bone marrow biopsy performed at our institution were evaluated. B5-fixed bone marrow core biopsies were reviewed for areas with the highest concentration of blasts. A tissue microarray was constructed using 1 mm cores. The cores were arrayed in duplicate in the majority of samples. Immunohistochemistry was performed for pSTAT5 with anti-pSTAT5 a/b Y695/99 mouse monoclonal antibody (AX1; Advantex Bioreagents) using automated stainers and heat-induced epitope retrieval. In each case, five hundred blasts were counted. The percentage of cells staining positive for pSTAT5 expression was determined by a pathologist blinded to clinical results. Standard metaphase karyotypes were classified into cytogenetic (CG) risk groups by CALGB criteria. Cox proportional hazards analysis was used to identify univariate and multivariate prognostic factors for CR, PFS, and OS, including age at diagnosis, history of an antecedent hematologic disorder (AHD), WBC at diagnosis, pSTAT5 expression, and CG risk group. Results: Adequate tissue and clinical data were available in 112 pts. The median age was 57 years, and median WBC at diagnosis 12.0 K/ μL. Twenty six percent of pts had favorable CG, 41% intermediate risk, 27% high risk, and 6% other (unknown or could not be classified). Nineteen percent of pts had an AHD. pSTAT5 expression was absent in 58% of pts. The remainder of the pts had: 1–5% pSTAT5 (25% of pts), 10% pSTAT5 (11% of pts), 20% pSTAT5 (4% of pts), 30% pSTAT5 (1% of pts), and 50% pSTAT5 (2% of pts). Seventy percent of all pts achieved a CR following induction chemotherapy. Sixty-four percent of pts received post-remission chemotherapy, 3.6% an autologous transplant, and 13.6% an allogeneic transplant in first CR. Median PFS and OS were 9.6 months and 16.0 months, respectively. On univariate analysis, age, history of AHD, WBC at diagnosis, CG risk, and any pSTAT5 expression were prognostic factors for PFS and OS. In multivariable analyses controlling for the above prognostic factors, pSTAT5 expression > 0 was also significantly associated with an increased risk of death (HR 1.96, 95% CI 1.19–3.23, p=0.008), progression or death (HR 1.64, 95% CI 1.01–2.66, p=0.046), and relapse after achieving CR (HR 2.31, 95% CI 1.16–4.63, p=0.018). pSTAT5 expression was not a predictor of achievement of CR. Conclusions: pSTAT5 expression in newly diagnosed adults with AML is associated with a decreased PFS, decreased OS, and increased risk of relapse. Validation of its prognostic value requires additional study. Agents targeting this signaling pathway might improve the outcome of pts with AML. Disclosures: No relevant conflicts of interest to declare.
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Keane, Colm, Linda Shen, Erica Han, Jamie P. Nourse, Rod Lea, Peter Mollee, Devinder S. Gill, and Maher K. Gandhi. "Tissue Microarray in DLBCL Patients receiving R-CHOP Chemo-Immunotherapy Shows Survival Benefit for Coexpression of LMO2/BCL6." Blood 118, no. 21 (November 18, 2011): 1585. http://dx.doi.org/10.1182/blood.v118.21.1585.1585.
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Abstract Abstract 1585 Background: Diffuse Large B-cell Lymphoma (DLBCL) is a heterogeneous disease with variable outcome within international prognostic index (IPI) categories. Previous studies indicate expression of germinal centre B-cell (GCB) markers predict good outcome and that non-GCB sub-types may benefit from alternate therapies. A variety of immunohistochemical combinations have been proposed. However results are inconsistent and there is limited data comparing strategies. The need for a robust, practical method to distinguish GCB-DLBCL remains. We evaluated co-expression of the GCB proteins LMO2 and BCL6 with the Choi, Hans and Tally algorithms in patients treated with R-CHOP chemo-immunotherapy. Patients and Methods: Seventy-five DLBCL patients, chosen solely on availability of material for tissue microarray, were studied using immunohistochemistry for FOXP1, MUM1, CD10, BCL6, LMO2 and GCET1 on original biopsies. Clinical data was obtained from a prospectively maintained database. Results were correlated with event free (EFS) and overall survival (OS). Results: The cohort was typical for DLBCL described in the literature with 63% of patients aged over 60. The International Prognostic Index (IPI) predicted overall survival (p<0.001) with 36% of patients with a low IPI score (0,1), 41% with intermediate score (2,3) and 23% with a high IPI score (4,5). The three year event free and overall survival (EFS and OS) were 68% and 73% respectively with a median follow up of 37 months. None of the cell of origin algorithm predicted for EFS or OS. The Hans (49%) and Choi algorithms (43%) typed similar number of patients as GCB but the Tally method (26%) typed patients less frequently as GCB. This difference was statistically different (p=0.014). No single marker predicted for outcome, however there was a trend for patients who were BCL6 positive to have improved outcome (p=0.06). 53% of patients were positive for BCL6. BCL6 was a significant predictor of improved event free survival on univariate analysis (p=0.016). Interestingly, patients who were positive for both LMO2 and BCL6 (26% of total) had a significantly improved outcome on univariate analysis for both event free (p=0.01) and overall survival (p=0.0036). LM02/BCL6 dual positivity retained significance for event free survival independent of IPI on multivariate analysis (p=0.017). It was not possible to demonstrate independence from IPI for overall survival using Cox regression as none of the nineteen dual positive patients have died. There was no significant differences between patients who were LMO2/BCL6 positive and the rest of the cohort with respect to any of the IPI factors. Of note, LMO2 on its own was independent of IPI with regards to overall survival despite not reaching significance at the univariate level (p=0.049). In the subgroup of patients who were positive for BCL6 approximately half were also positive for LMO2. There was a significant difference in overall survival between these BCL6 single positive and BCL6/LMO2 dual positive tumours (p=0.003) with improved outcome seen in the dual positive patients. Similarly those LMO2 positive patients who were BCL6 negative had very poor outcome compared to LMO2/BCL6 dual positive tumours (p=0.0002). Dual positivity for BCL6/LMO2 was strongly associated with germinal centre phenotype with eighty per cent of these patients typing for this cell of origin (p=0.0004). Germinal centre DLBCL as typed by the Choi algorithm could be separated into two significantly different groups with different overall survival based on LMO2/BCL6 dual positivity (p=0.01) Conclusion: LMO2/BCL6 dual positivity is a prognostic marker in DLBCL treated with R-CHOP that is independent of IPI, and predicts outcome in GCB typed tumours. Should these findings be prospectively validated, the strategy would be easily transferable to the diagnostic laboratory. Disclosures: No relevant conflicts of interest to declare.
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Fruchart, Christophe, Josette Briere, Renaud Ciappuccini, Olivier Casasnovas, Herve Tilly, Franck Morschhauser, Catherine Sebban, et al. "Upfront Consolidation Combining Yttrium-90 Ibritumomab Tiuxetan and High Dose Therapy with Stem-Cell Transplantation in Poor Risk Patients with Diffuse Large B-Cell Lymphoma." Blood 120, no. 21 (November 16, 2012): 812. http://dx.doi.org/10.1182/blood.v120.21.812.812.
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Abstract Abstract 812 Background: High dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) is considered as a relevant option for upfront consolidation in patients with poor risk aggressive lymphomas (Fitoussi, hematologica 2011; 96(8):1136-1143). Adding Y90-Ibritumomab Tiuxetan to BEAM regimen would improve outcomes in relapse or refractory lymphomas. We evaluated the safety and efficacy of standard-dose Y90-Ibritumomab Tiuxetan combined with high-dose BEAM after first line induction treatment in patients under 65 years of age with poor prognosis diffuse large B-cell lymphoma (DLBCL). (clinicaltrials.gov: NCT00689169). Methods and Patients: Pathologically proven CD20+ DLBCL patients, 18–65 years of age, with IPI ≥ 2, in CR, CRu or PR according to the IWG 1999 criteria after rituximab-containing induction therapy were included. Patients received Rituximab 250 mg/m2 on d-21, Rituximab 250 mg/m2 followed by Y90-Ibritumomab Tiuxetan 0.4mCi/kg on d-14, BEAM started on d-7 followed by ASCT. FDG-PET scans evaluated using Juweid criteria were performed before transplant in all patients, but were not decisional. Patients were analyzed by immunochemistry for CD10, BCL6, MUM1 and BCL2 expression. End of treatment assessment was done at day 100 (D100). The primary end point was event-free survival (EFS) at 2 years. Results: Seventy five consecutive patients were enrolled from August 2007 to December 2008. Median age was 49 years (19–64) with 7 pts (9%) older than 60 years. The IPI score was 2 in 28 pts (37%) and >2 in 47 pts (63%), bulky disease ≥ 10 cm in 29 pts (39%) and mediastinal involvement in 20 pts (26%). Thirty six patients received 4 (14 pts) or 6 (22 pts) cycles of R-CHOP and 39 had 4 cycles of R-ACVBP as induction treatment. After induction, 63 patients (84%) were in CR or CRu and 12 (16%) were in PR, 21 pts (28%) presented with positive PET. Four pts progressed before they completed the treatment including 2 with positive PET. Median follow-up was 34 months for the 71 patients eligible for analysis. Median time to reach a neutrophil count > 500/μL and platelet count > 20 000/μL was 11 days. Neutropenic fever (100%) and mucositis (78%) occurred in most patients. Other adverse events (AE) were usually mild to moderate in severity. Twenty three AE were reported as serious, mostly infection (n=9). One of them was fatal due to septic shock. The 2-yr EFS and overall survival (OS) was 79% (95% CI: 67–88%) and 83% (95% CI: 70–88%) respectively. Fourteen pts relapsed including 9 before D100. The Overall Response Rate (CR+CRu+PR) was 83%, 59 patients (81%) achieved a CR/CRu, 2 pts were in PR. The 2-year DFS was 91% (95% CI: 80% – 96%). There were no differences in OS (p=0.9) and EFS (p=0.8) between patients in CR/Cru or in PR. Positive PET imaging before transplant did not predict treatment failure. Nineteen pts with positive PET after induction were consolidated with Y90-Ibritumomab Tiuxetan and BEAM, one died of sepsis, 18 achieved a CR/CRu and 3 relapsed at 9, 14 and 20 month. Mediastinal involvement, non-GCB phenotype and high BCL2 expression did not affect outcome. IPI score (2 v >2) and bulky disease at diagnosis appeared to be prognosis factors for OS: 96% v 75% (p = 0.02) and 91% v 70% (p=0.02) respectively, but not for EFS: 2 years EFS 89% v 73% (p = 0.09) and 84% v 70% (p=0.1) respectively. Conclusions: Adding Y90 Ibritumomab Tiuxetan to BEAM is safe without an increase in transplant-related toxicity. First line consolidation with Y90 Ibritumomab Tiuxetan and HDT induced high rates of EFS and OS in poor prognosis patients with DLBCL irrespectively of PET status after induction treatment and warrants randomized study. Disclosures: Gisselbrecht: roche: Consultancy, Research Funding; baxter: Research Funding.
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Advani, Anjali, Sarah Gibson, Elizabeth Douglas, Tao Jin, Matt Kalaycio, Edward A. Copelan, Mikkael A. Sekeres, Ronald Sobecks, Shawnda Sungren, and Eric Hsi. "Histone H4 Acetylation as a Prognostic Factor for Patients with Acute Lymphocytic Leukemia in First Relapse." Blood 112, no. 11 (November 16, 2008): 1482. http://dx.doi.org/10.1182/blood.v112.11.1482.1482.
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Abstract Imbalances in histone acetylation can lead to changes in transcriptional dysregulation of genes involved in cell cycle progression and/or apoptosis. We have previously demonstrated that histone H4 acetylation is associated with improved relapse-free survival in newly diagnosed patients with acute lymphocytic leukemia (ALL) (Advani et al., ASH abstract #2798, 2007). However, the prognostic significance of histone acetylation in the relapsed setting is unclear. Therefore, we evaluated histone H4 acetylation in patients with ALL in first relapse, and the prognostic impact of acetylation on response to salvage therapy and overall survival (OS). Methods: From 1996 to 2007, patients with ALL in first relapse and an available diagnostic bone marrow biopsy performed at the Cleveland Clinic were evaluated. B5-fixed bone marrow core biopsies were reviewed for areas with the highest concentration of blasts. A tissue microarray was constructed using 1 mm tissue cores. The cores were arrayed in duplicate in the majority of samples. Immunohistochemistry was performed for acetyl-H4 (1:200 dilution; polyclonal; Upstate Biotech, Lake Placid, NY) using automated stainers and heat induced epitope retrieval. In each case, five hundred blasts were counted and only strong nuclear staining was classified as positive. Based on the distribution of cell counts, cases were classified as strongly positive if nuclear staining occurred in ≥ 40% of the blasts. Cytogenetic (CG) risk was defined by CALGB criteria. Cox proportional hazards analysis was used to identify univariate and multivariate risk factors for response to salvage therapy and OS at the time of relapse. Results: Thirty-nine patients had adequate tissue and clinical data for analysis. The median age at relapse was 39 yrs (range 20–67) and median time from diagnosis to first relapse was 13.2 months (range 1.4–39.0). Seventy-nine percent of patients had ALL derived from B-cell, 18% T-cell, and 3% mixed lineage. Thirty-one percent of patients had poor risk CG, 46% normal karyotype, 10% miscellaneous abnormalities, and 13% unknown CG. At the time of relapse, 13% of patients had central nervous system involvement in addition to blood/bone marrow disease. Thirty-three pts (85%) had acetylated histone H4. Most patients received re-induction with a high-dose cytarabine-based regimen (48%). However, the remainder received anthracycline/vincristine/prednisone (30%), methotrexate/vincristine/asparaginase/decadron (13%), or clofarabine/cytarabine (9%). Ten pts (26%) achieved a complete remission (CR) after salvage therapy. Nineteen pts (49%) proceeded to allogeneic bone marrow transplant (BMT) with a related or unrelated donor. The median OS for all patients was 6.1 months. The median OS for pts proceeding to BMT was superior to pts not proceeding to BMT (12.8 months versus 4.7 months, p<0.001). There was a trend towards an improved OS after relapse in patients with histone acetylation, HR=0.40, 95% CI 0.16–1.03, p=0.058 on univariate analysis. This trend remained on multivariate analysis when age, time from diagnosis to relapse, CG risk group, and immunophenotype were included in the analysis (HR=0.40, 95% CI 0.13–1.20, p=0.10). No patients with non-acetylated histone H4 were able to proceed to BMT because of refractory disease or death/complications related to salvage therapy. Conclusions: Acetylation of histone H4 is associated with a trend towards an improved OS in patients with ALL in relapse. This may be related to the fact that no patients with non-acetylated histone H4 were able to proceed to BMT. Although this data will need to be evaluated prospectively in a larger number of patients, this data provides rationale for the incorporation of histone deacetylase inibitors into salvage regimens for patients with relapsed/refractory ALL, particularly in patients not expressing acetylated histone H4.
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macconnell, scott. "Jean-Louis Vignes: California's Forgotten Winemaker." Gastronomica 11, no. 1 (2011): 89–92. http://dx.doi.org/10.1525/gfc.2011.11.1.89.
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This article represents a first step in the process of restoring the legacy of pioneer California winemaker Jean-Louis Vignes (1780–1862). Vignes was a native of France who established and operated a commercial winery (El Aliso) in Los Angeles for 22 years (1833–1855). The article includes the first known photograph of Vignes discovered by the author. While prominent twentieth-century American wine historians have acknowledged Vignes, the author emphasizes a key distinction made by French historian Leonce Jore. Vignes left France to go to the Sandwich Islands as part of a commercial enterprise that traveled with Catholic missionaries (Picpus Fathers). Only after five years of frustration did Vignes move to Los Angeles and establish a winery. The author uses the remembrances of well-known nineteenth-century commentator William Heath Davis [Seventy-Five Years in California (San Francisco, 1929)] to give some personal insights into Vignes as a winemaker. Davis visited him at El Aliso three times as a young man and lived long enough (1909) to validate Vignes’s vision for the potential of winemaking in California. The article also includes the first known full citation for Vignes’s gravesite at Evergreen Cemetery in Los Angeles.
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Arhin, Kwame. "A note on the Asante akonkofo: a non-literate Sub-elite, 1900–1930." Africa 56, no. 1 (January 1986): 25–31. http://dx.doi.org/10.2307/1159731.
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Opening ParagraphFollowing the growing interest in recent years in social stratification in Asante in the nineteenth and twentieth centuries (Arhin, 1983a: 2–22; 1983b: 475; McCaskie, 1983: 23–44; Wilks, 1975: 166–719), this note offers a preliminary study of a body of men who became known in Kumasi and the capital towns of the other Asante chiefdoms – in particular Bekwai, Juaben and Mampon – as the akonkofo in the first phase of colonial rule, 1896–1930. The argument of the paper, written in the light of the views of Daaku (1970, 1971) is that the akonkofo, an intermediary group between office holders and non-holders of office (Arhin, 1983a) could emerge as a distinctive sociopolitical category only in the colonial period. The first section of this article, on the origin of the akonkofo, describes the factors that inhibited the rise of ‘merchant princes’ in Asante before colonial rule; the second, on the akonkofo in Kumasi, offers a kind of social portrait of the akonkofo; and the third section, on the position of the akonkofo in Asante society, examines the relationship of the akonkofo to traditional authority. My sources are archival and written. I have also recorded interviews with Barima Owusu-Ansah, over seventy-five years old, and a leading authority on Asante law and constitution, and with Baffour Osei Akoto, senior spokesman (okyeame) of the Asantehene and just turned seventy, as well as conversations with sundry officials at the Asantehene's court.
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Virág, Ágnes. "Multimodal conceptual patterns of Hungary in political cartoons." Cognitive Linguistic Studies 7, no. 1 (August 19, 2020): 222–53. http://dx.doi.org/10.1075/cogls.00055.vir.
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Abstract Conventionalized positive images of Hungary have been overemphasized in political caricatures ever since the nineteenth century (Tamás 2012, 2014). The present article explores the multimodal representations of hungary in cartoons in the period between 1989 and 1990, during which negative images of Hungary became prominent due to the weak financial situation of the country and the political system change. The corpus involves seventy-five cartoons from the satirical magazine Ludas Matyi. Two major claims are justified by adopting Paula Pérez-Sobrino’s (2017) multimodal identification procedure: (1) the interpretation of verbal elements (e.g., labels, verbal texts, and verbal symbols) in political cartoons influences the identification of multimodal conceptual patterns; (2) the dominant patterns that structure the representation of hungary in political cartoons are metonymy-based visual and multimodal metaphors, and both of them occur in metaphorical scenarios. The corpus analysis indicates that the two main target frames, financial crisis and political changes, appear through the sources of human body and object in metaphorical scenarios, such as ordinary scenes, motion, hospital, sport, tale, love, feast, stunt, begging, and church scenes. Apart from identifying the representations of Hungary, visual metonymies as well as textual cues need to be revealed in order to understand what metaphtonymy scenarios are intended in the cartoons.
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"Role of Minimal Invasive Thoracic Surgery in Thai Lung Cancer Patients." Journal of the Medical Association of Thailand 104, no. 6 (June 15, 2021): 916–20. http://dx.doi.org/10.35755/jmedassocthai.2021.06.12472.
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Objective: To assess the outcome of minimal invasive surgery in terms of intra and post-operative complication, length of tube duration, hospital stay, and cost-effective in lung resection of Thai urban population that underwent video assisted thoracoscopic surgery (VATS) and open thoracotomy (OT). Materials and Methods: The present study was a retrospective cohort between 2006 and 2019. One hundred seventy-eight patients underwent pulmonary resection. All patients were diagnosed either primary or secondary lung cancer. All medical records were collected at Vajira Hospital. All various factors were analyzed to evaluate an outcome between both groups. Results: One hundred nineteen patients were performed by VATS, whereas 59 patients were performed by OT. Tube duration and length of hospital stay were shorter in VATS groups with five days versus seven days (p=0.001) and six days versus eleven days (p=0.001). The operative time was longer and more blood loss in OT groups compare to VATS groups with 180 minutes versus 70 minutes (p=0.001) and 100 mL versus 20 mL (p=0.001). In post-operative outcome, there was no difference in terms of arrhythmia, pneumonia, and 30 days mortality. However, there were slightly higher cost during hospital stay in VATS compared to OT at 3,329.9 USD versus 2,685.7 USD (p=0.001). Conclusion: VATS is associated with shorter length of tube duration, hospital stay, and less blood loss with no difference of post-operative outcome in lung cancer patients. Keywords: Video assisted thoracoscopic surgery; cancer; open thoracotomy
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Mehta, Sharuti, Anil Kumar Sharma, and Rajesh Kumar Singh. "Ethnobotany, Pharmacological activities and Bioavailability studies of “King of Bitter” (Kalmegh): A Review (2010-2020)." Combinatorial Chemistry & High Throughput Screening 24 (March 10, 2021). http://dx.doi.org/10.2174/1386207324666210310140611.
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Background: Andrographis paniculata, commonly known as “Kalmegh”, is an annual herbaceous plant from family Acanthaceae. The whole plant of A. paniculata has explored for multiple pharmacological activities and is scientifically recognized by in-vivo and in-vitro studies. Various biotechnologically engineered techniques have been explored to enhance the bioavailability of this plant. Objective: In this review, we aim to present comprehensive recent advances in the ethnopharmacology, phytochemistry, specific pharmacology, safety and toxicology and bioavailability of A. paniculata and its pure compounds. Possible directions for future research are also outlined in brief, which will encourage advance investigations on this plant. Methods: Information on the recent updates of the present review is collected from different electronic scientific databases such as Science Direct, PubMed, Scopus, and Google Scholar. All the composed information is classified into different sections according to the objective of the paper. Results: More than hundred research and review papers have been studied and incorporated in the present manuscript. After vast literature search of A. paniculata, we present a noteworthy report of various phytoconstituents present in plant, which are accountable for potential therapeutic properties of the plant. Forty-five of studied articles give general information about introduction, ethnobotany and traditional uses of the plant. Twenty-two papers enclosed information about the phytoconstituents present in different parts of A. paniculata and seventy-two papers briefly outlined the pharmacological activities like antioxidant, anti-dengue, anti-ulcerogenic, antifungal, some miscellaneous activities like activity against SARS-CoV-2, antidiarrhoeal. Nineteen studies highlighted the research work conducted by various researchers to increased bioavailability of A. paniculata and two studies reported the safety and toxicology of the plant. Conclusion: This review incorporated the scientifically validated research work encompassing the ethnobotanical description of the subjected plant, phytochemical profile, various pharmacological activities, and recent approaches to enhance the bioavailability of active metabolites.
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Alkhayat, Nawaf, Mohammad Alshahrani, Ghaleb Elyamany, Qanita Sedick, Walid Ibrahim, Hasna Hamzi, Amal Binhassan, et al. "Clinicopathologic features and therapy outcome in childhood Hodgkin’s lymphoma: a report from tertiary care center in Saudi Arabia." Journal of the Egyptian National Cancer Institute 33, no. 1 (August 16, 2021). http://dx.doi.org/10.1186/s43046-021-00078-0.
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Abstract Background Hodgkin lymphoma (HL) is lymphoid neoplasm usually affecting lymphatic system; it accounts 3.6% of cancers in Saudi Arabia. Modern treatment protocols had shown particular success rates in overall-survival (OS) and event-free-survival (EFS). In our study, we reviewed the medical records of 80 pediatric and young adolescent patients diagnosed HL from January 2006 to July 2020, treated at tertiary care hospital in Riyadh, Saudi Arabia. Demographic, clinical, and pathological data were explored. First line therapy was ABVD, COG, COPP, R-CHOP, or radiotherapy alone in 53/80 (66.4%), 24/80 (30%), 1/80 (1.2%), 1/80 (1.2%), or 1/80 (1.2%) patients; respectively. Response assessment was done by CT + / − PET scan after first 2 cycles then every 2 cycle and end of therapy. Another assessment was done if any clinical suspicion of recurrence. Results Median age 11 (range 3–16) years. Males to females 1.3:1. Seventy-two out of eighty (90%) patients showed first complete remission (CR1) and maintained remission for median 40 (range 7–136) months. Eight out of eighty (10%) patients showed refractory disease. Nineteen patients received salvage therapy (ICE or ESHAP/brentuximab vedotin or gemcitabine/brentuximab vedotin), 14/19 (73.7%) had 2nd complete remission (CR2) for median time 24 (ranged 9–78) months, while 5/19 (26.3%) did not show any response. Five-year OS and EFS were 95% and 75%. Two patients had 2ry malignant neoplasms, one had AML and died, the other had malignant fibrous histocytoma and still alive. None of our patients had fertility problem. Also, they did not experience chronic pulmonary or cardiotoxicity. Classic Hodgkin’s lymphoma: nodular sclerosis subtype was more prominent (55%) than mixed cellularity subtype (22.5%), which is similar to several European and US studies, lymphocyte rich (11.25%) and lymphocyte depleted (0%), while nodular lymphocyte predominant Hodgkin’s lymphoma (11.25%). Conclusions Our study provided unique descriptive study of childhood HL, in Saudi Arabia, with valuable insight into the long-term outcome and late toxicity. Our results are comparable to other studies in the Middle East and European countries.
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Agar, Georgie, Chloe Brown, Daniel Sutherland, Sean Coulborn, Chris Oliver, and Caroline Richards. "Sleep disorders in rare genetic syndromes: a meta-analysis of prevalence and profile." Molecular Autism 12, no. 1 (February 25, 2021). http://dx.doi.org/10.1186/s13229-021-00426-w.
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Abstract Background Sleep disorders are common in people with intellectual disability (ID) and autism, with growing evidence of diverse sleep profiles across ID associated genetic syndromes. Documenting the prevalence and profile of specific sleep disorders in syndromes will quantify syndrome-driven ‘risk’, inform prognosis and enhance understanding of aetiology of sleep disorders. Method Following PRISMA guidelines for meta-analysis, we searched Ovid PsycINFO, Ovid MEDLINE, Ovid Embase, Web of Science and PubMed Central with use of syndrome-specific keywords and 60 sleep-related search terms. We screened and extracted papers that reported sleep disorder prevalence data for five or more individuals within a genetic syndrome, and applied quality criteria to produce a quality-effects prevalence model of six types of sleep disorder across nineteen syndromes. Relative risk estimates were calculated for the prevalence of each sleep disorder in each syndrome. Results Two hundred and seventy three papers were identified, generating 463 prevalence estimates for Angelman, CHARGE, Cornelia de Lange, Down, fragile X, Prader–Willi, Rett, Smith–Magenis and Williams syndromes, mucopolysaccharidoses (MPS disorders), neurofibromatosis and tuberous sclerosis complex. Prevalence estimates were higher in genetic syndromes than published equivalents for typically developing individuals, with few exceptions. Between-syndrome differences for some disorders were evident; sleep-disordered breathing was most prevalent in MPS disorders (72–77%), while excessive daytime sleepiness was highest in Smith–Magenis syndrome (60%). Conversely, insomnia, which was reported at a higher rate than TD estimates in all syndromes except fragile X, was not associated with specific genetic risk. This suggests insomnia could emerge because of the individual’s environment or associated developmental delay, rather than any specific genetic syndromes. Limitations Due to the broad scope of the meta-analysis, only syndromes previously identified as reporting preliminary sleep research were included. Other syndromes may also experience elevated prevalence rates of specific types of sleep disorder. Only English language papers were included. Conclusions Differing prevalence rates between types of sleep disorder suggest differing causal mechanisms, such as cranio-facial morphology in Down and Prader–Willi syndromes and the build-up of mucopolysaccharides in MPS disorders. Priorities for clinical assessment and intervention for sleep disorders are discussed.
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"Group Work Practices of Social Work Effecting In Changing the Integrated Child Development Programes in India and How Can It Change the World Problem." Journal of Nursing & Healthcare 3, no. 1 (January 10, 2018). http://dx.doi.org/10.33140/jnh/03/01/00001.
Full textAbstract:
Nineteen per cent of world’s children live in India. Of all the children in the world, one in five is an Indian. India is home to more than one billion people, of which 42 per cent are children, defined as persons under 18 years of age. Women and children constitute seventy two percent of the population of India. The women and children homogenous whole. A great deal of heterogeneity exist. The form of marginalize and vulnerable group of sc, st, obc, and other religious minorities suffer multiple challenge. Women from these group and even more disadvantages as they are subject to additional discrimination on account of societal construct of gender and the consequently adverse power balance. The main problem with the minorities is that no proper database of these have been done. The Integrated Child Development Services (ICDS) Scheme since 1975 for delivery of an integrated package of services relating to health, nutrition and non-formal education to children in the age group 0-6 years, pregnant women and nursing mothers. This package is aimed at improvement in the nutritional and health status of children in this age group, reduction in the incidence of mortality, morbidity, malnutrition and school drop-out rates, and enhancement of the capability of the mother to look after the health and nutritional needs of the child through proper nutrition and health education In short, these objectives which envisage the laying of the foundation for the proper psychological, physical and social development of the child, with appropriate support from the mother, aim at the ultimate goal of human resource development, in its broadest sense. The twin objective of this strategy being comprehensive child development and family welfare, effective coordination in the states, between the departments and agencies that are responsible for the major inputs in the program Wherever this convergence of the maternal and child health services and the ICDS program have been achieved Early childhood period (0-6 years) deserves special attention. It is due to the fact of accumulated scientific evidences that powerfully demonstrates in instituting either family and or centre based early childhood interventions so as to nurture (i) psycho - social development (cognition, motor, social, emotional and language) through maturation and interaction in an properly designed appropriate environment suiting to the child and (ii) generating long term social, economic and educational benefits in terms of lower rates of grades repetition; increased earning potential; reduction in juvenile delinquency; increased social mobilization; reduced social and economic inequalities; psycho - social readiness for school; reduction of drop out rate ; expanding universalization of elementary education ; improved parent - child interaction and finally reducing high developmental costs at later stage of life due to inadequate care. Numerically also, children less than 6 years of age constitute about 15 % of the total population. Of the total child population, 2.07 crore (6 per cent) are infants who are below 1 year; 4.17 crore (12 per cent) are toddlers in the age group of 1-2 years; and 7.73 crores (22.2 per cent) are pre scholars in the age group of 3-5 years. Thus one of the salient demographic features of our country is that it has a sizeable proportion of young population. India is not only home to 21 per cent of developing world’s young children but its young child population size is larger than the total population size of many countries. In 2016, about 25 million infants were immunization services and their mothers will require maternal health services. Similarly, pre school education services will need to be provided for 72 million children in 2016. No other nation in the world including China is likely to enjoy the benefits of such a large young population. This was done with the help of ICDS Programe. By using group work Today, social workers are not only the bridge linking clients to other helpers, they also provide their clients with hope, and encourage their first steps towards a new life. Social workers usually stand in the front line, and reach out to the clients soon after problems occur. They provide an initial assessment of the situation and mobilize other needed services. Social work uses a team approach and is multi-disciplined. Its goal is to provide a service to those who need help.