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1

Kutluk, M. Tezer, and Akif Yeşilipek. "Pediatric cancer registry in Turkey 2009-2020 (TPOG & TPHD)." Journal of Clinical Oncology 39, no. 15_suppl (2021): e22519-e22519. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e22519.

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e22519 Background: Global actions on pediatric cancer control is targeting to improve the survival rates in low and middle income countries which already exceeded 80% in high income countries. Almost 300.000 pediatric cancer cases annually are expected in children and adolescents aged 0-14 globally. Pediatric cancer registry must be a priority within the pediatric cancer control programs. Here, we present the most updated results of the pediatric cancer registry in Turkey. Methods: Pediatric cancer registry has been established by the Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association in 2002. The childhood cancer cases registered between 2009-2020 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 12 years from 2009 to 2020, 21792 cases were registered. For all cases, median age was 6.7 year (0-19; M/F 12198/9584, 4 hermaphrodite, 6 unknown). Age distribution was 0-4 yrs, 40.9%; 5-9 yrs, 23.7%; 10-14 yrs, 23.4%; 15-19 yrs, 12.0%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (5208, 23.9%, 5.5, 3004/2204); Lymphoma & other RES tumors (4103, 18.8%, 9.8, 2733/1367, 1 hermaphrodite & 2 unknown); CNS [brain & spinal] (3269, 15.0%, 6.8, 1794/1474, 1 unkown); Symphatetic system (1794, 8.2%, 2.4, 933/861); Retinoblastoma (610, 2.8%, 1.4, 339/271); Renal (1079, 5.0%, 3.1, 524/553, 1 hermaphrodite & 1 unknown); Liver (376, 1.7%, 2.2, 216/160); Malignant bone (1448, 6.6%, 12.5, 787/661); Soft tissue sarcomas (1554, 7.1%, 7.6, 888/666); Germ cell (1461, 6.7%, 9.3, 547/910, 2 hermaphrodite, 2 unknown); Carcinoma & other malignant epithelial (745, 3.4%, 13.5, 362/383); Other/non-specific malignant (145, 0.7%, 7.9, 71/74). Five year survival rate was found as 72%. Conclusions: This registry shows the imrovement of survival rates to 72% in Turkey which is comparable with middle income countries. The pediatric cancer control community is investing on the control of childhood cancer for further improvement and this registry became a valuable source for pediatric oncology community at national and international level.
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Hulin, Cyrille, Thierry Facon, Chaim Shustik, et al. "Effect of Age on Efficacy and Safety Outcomes in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Receiving Lenalidomide and Low-Dose Dexamethasone (Rd): The First Trial." Blood 124, no. 21 (2014): 81. http://dx.doi.org/10.1182/blood.v124.21.81.81.

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Abstract Background: In the pivotal FIRST trial, a randomized, international, multicenter phase 3 study, continuous Rd compared with melphalan-prednisone-thalidomide (MPT) improved progression-free survival (PFS) which was the primary endpoint (HR = 0.72; P < 0.01). The interim overall survival (OS) analysis showed a 22% reduction in risk of death with continuous Rd vs. MPT (HR = 0.78; P = 0.02) (Facon, Blood 2013). This analysis evaluates outcomes based on age, which was a stratification parameter, and compared pts aged ≤ 75 yrs and > 75 yrs. Methods: Pts with NDMM were randomized to continuous Rd until progressive disease (PD) (N = 535); 18 cycles (72 weeks [wks]) of Rd (Rd18; N = 541); or 12 cycles (72 wks) of MPT (N = 547). Starting doses were reduced in pts aged > 75 yrs: dexamethasone (20 vs. 40 mg), melphalan (0.20 vs. 0.25 mg/kg), and thalidomide (100 vs 200 mg). The primary endpoint was PFS (continuous Rd vs. MPT) and the secondary endpoint were OS, overall response rate, time to response, duration of response, time to Tx failure, time to 2nd AMT, health-related quality of life, safety. Results: The proportion of pts aged > 75 yrs was > 34% across treatment (Tx) arms. In pts ≤ 75 yrs, 37% had ISS stage III vs. 51% in > 75 yrs. ECOG score ≥ 1 was observed in 74% and 69% of pts aged > 75 and ≤ 75 yrs, respectively. Severe renal impairment (CrCl < 30 mL/min) was observed in 14% of pts > 75 vs. 7% in ≤ 75 yrs. PFS and OS outcomes favored continuous Rd over MPT in both age groups. With a median follow-up of 37 months (mos), PFS was 27.4 mos in continuous Rd pts vs. 21.8 mos in MPT pts aged ≤ 75 yrs (HR = 0.68; P < 0.001); a trend for improved PFS was also seen for pts aged > 75 yrs (HR = 0.81; P = 0.11) (Table 1). PFS for continuous Rd vs. Rd18 pts was also increased in both age groups (HR = 0.68; P < 0.001 and HR = 0.75; P = 0.03, respectively). Response rates were consistently higher with continuous Rd vs. MPT in pts aged ≤ 75 yrs (77% vs. 66%; P < 0.001) and > 75 yrs (71% vs. 55%; P < 0.001). Duration of response with continuous Rd was longer vs. MPT in pts aged ≤ 75 yrs (40 vs. 22 mos) and pts > 75 yrs (31 vs. 24 mos). The interim analysis of OS showed an improved trend for continuous Rd vs. MPT in pts aged ≤ 75 yrs (HR = 0.77; P = 0.06) and > 75 yrs (HR = 0.80; P= 0.16). Grade 3–4 adverse events (AEs) in ≥ 10% of pts were similar across age subgroups (Table 2). Tx discontinuation due to AEs was comparable across the Tx groups and independent of age. Conclusions:Regardless of age (≤ 75 vs. > 75 yrs), continuous Rd was effective, increased PFS and interim OS, and was generally well tolerated vs. MPT in NDMM pts. Duration of response was improved with continuous Rd vs. MPT and Rd18, irrespective of age, and with a more profound benefit observed in younger pts. Continuous Rd represents a new clinical option and standard of care for these pts in the first-line setting. Abstract 81. Table 1 PFS, OS and Response Aged ≤ 75 yrs Aged > 75 yrs All pts ITT population Continuous Rd (n = 349) Rd18 (n = 348) MPT (n = 359) Continuous Rd (n = 186) Rd18 (n = 193) MPT (n = 188) Continuous Rd (n = 535) Rd18 (n = 541) MPT (n = 547) Median PFS, mos 27.4 21.3 21.8 21.2 19.4 19.2 25.5 20.7 21.2 PFS HR (95% CI); P-value Continuous Rd vs. Rd18 0.68 (0.55–0.83); P < 0.01 0.75 (0.58–0.98); P = 0.03 0.70 (0.60–0.82); P < 0.01 Continuous Rd vs. MPT 0.68 (0.56–0.83); P < 0.01 0.81 (0.62–1.05); P = 0.11 0.72 (0.61–0.85); P < 0.01 4-yr OS, % 66 61 58 47 47 39 59 56 51 OS HR (95% CI); P-value Continuous Rd vs. Rd18 0.88 (0.67–1.16); P = 0.36 0.94 (0.69–1.29); P = 0.70 0.90 (0.73–1.10); P = 0.31 Continuous Rd vs. MPT 0.77 (0.59–1.01); P = 0.06 0.80 (0.59–1.09); P = 0.16 0.78 (0.64–0.96); P = 0.02 Response rate (≥ PR), % 77 77 66 71 66 55 75 73 62 Duration of response (≥ PR), mos 40 23 22 31 20 24 35 22 22 CI, confidence interval; ITT, intent to treat; PR, partial response. Table 2 Grade 3–4 AEs Observed in ≥ 10% of Pts Aged ≤ 75 yrs Aged > 75 yrs Safety population, % Continuous Rd (n = 347) Rd18 (n = 348) MPT (n = 357) Continuous Rd (n = 185) Rd18 (n = 192) MPT (n = 184) Neutropenia 28 25 47 28 29 40 Thrombocytopenia 8 9 13 9 7 7 Anemia 18 12 20 19 23 17 Leukopenia 5 6 11 4 5 8 Infections 29 21 16 29 23 20 DVT and/or PE 10 6 8 7 8 4 Peripheral sensory neuropathy 1 1 10 1 0 8 Tx discontinuation due to AEs 28 18 28 32 25 30 DVT, deep-vein thrombosis; PE, pulmonary embolism. Disclosures Hulin: Celgene: Honoraria. Off Label Use: Lenalidomide used in newly diagnosed multiple myeloma patients. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Belch:Janssen, Celgene, Onyx: Honoraria. Petrucci:Celgene, Janssen-Cilag, Sanofi, Bristol-Myers Squibb: Honoraria. Dührsen:Celgene: Honoraria, Research Funding. Song:Celgene: Consultancy, Honoraria, Research Funding. Houck:Celgene: Employment. Chen:Celgene: Employment. Ervin-Haynes:Celgene: Employment.
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Makanya, A. N., J. N. Maina, T. M. Mayhew, S. A. Tschanz, and P. H. Burri. "A stereological comparison of villous and microvillous surfaces in small intestines of frugivorous and entomophagous bats: species, inter-individual and craniocaudal differences." Journal of Experimental Biology 200, no. 18 (1997): 2415–23. http://dx.doi.org/10.1242/jeb.200.18.2415.

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The extents of functional surfaces (villi, microvilli) have been estimated at different longitudinal sites, and in the entire small intestine, for three species of bats belonging to two feeding groups: insect- and fruit-eaters. In all species, surface areas and other structural quantities tended to be greatest at more cranial sites and to decline caudally. The entomophagous bat (Miniopterus inflatus) had a mean body mass (coefficient of variation) of 8.9 g (5%) and a mean intestinal length of 20 cm (6%). The surface area of the basic intestinal tube (primary mucosa) was 9.1 cm2 (10%) but this was amplified to 48 cm2 (13%) by villi and to 0.13 m2 (20%) by microvilli. The total number of microvilli per intestine was 4 x 10(11) (20%). The average microvillus had a diameter of 8 nm (10%), a length of 1.1 microns (22%) and a membrane surface area of 0.32 micron 2 (31%). In two species of fruit bats (Epomophorus wahlbergi and Lisonycteris angolensis), body masses were greater and intestines longer, the values being 76.0 g (18%) and 76.9 g (4%), and 73 cm (16%) and 72 cm (7%), respectively. Surface areas were also greater, amounting to 76 cm2 (26%) and 45 cm2 (8%) for the primary mucosa, 547 cm2 (29%) and 314 cm2 (16%) for villi and 2.7 m2 (23%) and 1.5 m2 (18%) for microvilli. An increase in the number of microvilli, 33 x 10(11) (19%) and 15 x 10(11) (24%) per intestine, contributed to the more extensive surface area but there were concomitant changes in the dimensions of microvilli. Mean diameters were 94 nm (8%) and 111 nm (4%), and mean lengths were 2.8 microns (12%) and 2.9 microns (10%), respectively. Thus, an increase in the surface area of the average microvillus to 0.83 micron 2 (12%) and 1.02 microns 2 (11%) also contributed to the greater total surface area of microvilli. The lifestyle-related differences in total microvillous surface areas persisted when structural quantities were normalised for the differences in body masses. The values for total microvillous surface area were 148 cm2g-1 (20%) in the entomophagous bat, 355 cm2g-1 (20%) in E. wahlbergi and 192 cm2g-1 (17%) in L. angolensis. This was true despite the fact that the insecteater possessed a greater length of intestine per unit of body mass: 22 mm g-1 (8%) versus 9-10 mm g-1 (9-10%) for the fruit-eaters.
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Santos, G. M. G., K. C. Silva-Santos, T. R. R. Barreiros, et al. "233 HIGH NUMBERS OF ANTRAL FOLLICLES INFLUENCE THE IN VITRO EMBRYO PRODUCTION, BUT NOT THE CONCEPTION RATE OF FIXED-TIME ARTIFICIAL INSEMINATION IN NELORE CATTLE." Reproduction, Fertility and Development 27, no. 1 (2015): 206. http://dx.doi.org/10.1071/rdv27n1ab233.

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The aim of this study was to compare the conception rates to fixed-time artificial insemination (FTAI) and in vitro embryo production between Nelore cows with high or low antral follicle counts (AFC). First, multiparous Nelore cows (Bos indicus, n = 547, 40–60 days postpartum) were subjected to synchronization of ovulation. Randomly during their oestrous cycle (Day 0), cows received an intravaginal device containing 1.9 g of P4 (CIDR®) and 2 mg of oestradiol benzoate (Estrogin®), intramuscularly. At device removal (Day 8), cows received 500 µg of PGF2α (Ciosin®), 300 IU of eCG (Novormon®), and 1 mg of oestradiol cipionate (ECP®), intramusculary. All cows were inseminated 48 h after P4 device removal. Antral follicles = 3 mm were counted using an intravaginal microconvex transducer (Day 0), and cows were assigned to groups of high (G-High, = 25 follicles, n = 183), intermediate (G-Intermediate, 16–20 follicles, n = 183), or low AFC (G-Low, = 10 follicles, n = 181). In another study to compared the in vitro embryo production, Nelore cows (n = 66, 72–96 months) were subjected to ultrasound-guided follicular aspiration using an intravaginal microconvex array transducer (7.5 MHz). The COC were selected and cows were assigned to groups according to the oocyte production: G-High (n = 22, = 40 oocytes), G-Intermediate (n = 25, 18–25 oocytes), or G-Low (n = 19, = 7 oocytes). Previously tested semen from a single bull was used for IVF using a previously described protocol (Silva-Santos et al. 2014 Reprod. Domest. Anim. 49, 228–232). The oocyte and embryo production (viable embryo: grade I, II, III; vitrifiable embryo: grade I, II) were evaluated. The number of follicles was evaluated by Kruskal-Wallis, and the chi-square test was used for data on oocyte and embryo production (P = 0.05). The average follicular population was 30.7 ± 5.7 (G-High), 18.6 ± 1.64 (G-Intermediate), and 7.8 ± 2.4 follicles (G-Low; P < 0.05), but there were no differences in the conception rates among groups (51.9 v. 48.6 v. 58.6%, respectively; P > 0.05). The total number of oocytes recovered were 1109 (G-High), 534 (G-Intermediate), and 101 (G-Low; P < 0.05). The mean number of viable oocytes was 40.4 ± 10.6 (G-High), 14.8 ± 3.0 (G-Intermediate), and 3.8 ± 1.1 (G-Low; P < 0.05) and the percentage of viable oocytes was 80% (G-High), 69% (371/534, G-Intermediate), and 71% (G-Low; P < 0.05). Cleavage rate was 79% (G-High), 74% (348/472, G-Intermediate), and 71% (G-Low; P < 0.05), and blastocyst rate was 42% (G-High), 32% (153/472, G-Intermediate), and 13% (G-Low; P < 0.05). The number of viable embryos was 18.4 ± 6.7 (G-High), 6.1 ± 3.6 (G-Intermediate), and 0.6 ± 0.7 (G-Low; P < 0.05) and the percentage of vitrifiable embryos was 81% (G-High), 77% (118/153, G-Intermediate), and 58% (G-Low; P < 0.05). Therefore, Nelore cows with high oocyte production had ~10-fold higher oocyte production and produced ~30-fold more embryos compared with the low AFC group. In conclusion, AFC had no influence on the conception rates to FTAI; however, Nelore cows with high oocyte production exhibited higher in vitro embryo production.
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Перескоков, Михаил Львович, та Дарья Алексеевна Якимова. "ОПЫТ СТАТИСТИЧЕСКОГО И ПРОСТРАНСТВЕННОГО АНАЛИЗА КЕРАМИКИ ГЛЯДЕНОВСКОГО КОСТИЩА (ПО МАТЕРИАЛАМ РАСКОПОК 2015–2018 ГОДОВ): ПЕРВЫЕ РЕЗУЛЬТАТЫ". Археология Евразийских степей, № 2 (30 квітня 2021): 175–90. http://dx.doi.org/10.24852/2587-6112.2021.2.175.190.

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В статье представлены результаты апробации комплексной методики изучения керамического материала Гляденовского костища (конец VI в. до н.э. – V в. н.э.). Гляденовское костище – сложный культовый объект, имеющий слабо стратифицированный культурный слой, что существенно усложняет решение вопросов хронологии памятника. Предлагаемая методика может помочь в решении данной задачи. Исследование включало следующие этапы. Была создана база данных керамики, которая отражает качественные признаки орнаментации. Статистическая таблица учитывала технику нанесения орнамента, отдельные элементы орнамента, комбинации элементов – орнаментальные мотивы, а так же и орнаментальные композиции в целом. Сложные композиции дают уникальный набор признаков. Данные представлены в бинарном коде и подвержены статистическому анализу, который выполнялся последовательно двумя методами: кластерным иерархическим анализом и методом главных компонент. После этого, полученные результаты кластеризации и группировки распределения в координатах ГК. Выделенные кластеры и группы отражают стилистические и хронологические особенности керамики Гляденовского костища. После этого инструментами ГИС проведен пространственный анализ расположения керамического материала в пространстве культурного слоя, с учетом результатовстатистического анализа. Подтвержден стратиграфический принцип формирования культурного слоя костища. Выявлены особенности распределения различных типов керамики в пространстве памятника.
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Pruskowski, Kaitlin A., and Leopoldo C. Cancio. "507 Outcomes After the Administration of Hydroxocobalamin." Journal of Burn Care & Research 41, Supplement_1 (2020): S90. http://dx.doi.org/10.1093/jbcr/iraa024.139.

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Abstract Introduction Hydroxocobalamin is administered to patients after injures sustained during structure fires or fires in enclosed spaces. It is unknown how the administration of hydroxocobalamin affects patient outcomes, however, there have been reports of increased risk of acute kidney injury (AKI). The purpose of this study was to determine the population in which hydroxocobalamin is administered and to assess outcomes in patients who receive this medication in the ICU setting. Methods This was a retrospective chart review that included all patients admitted to the burn ICU between July 2016 and April 2019. Patients were included if they received hydroxocobalamin after ICU admission. Patients who received hydroxocobalamin in the pre-ICU or pre-hospital setting were not included in this analysis. Data collected included demographic information, number of hydroxocobalamin doses administered, burn size (% TBSA), presence of inhalation injury (II), lactate levels during the first 72 hours of hospitalization, carboxyhemoglobin levels, need for continuous renal replacement therapy (CRRT), and in-hospital mortality. Results Thirty-five patients received hydroxocobalamin after ICU admission. Patients were, on average, 48 ± 19 years old with a 25.5 ± 24.8% TBSA burn. Twenty-nine patients (82.9%) who received hydroxocobalamin in the ICU were diagnosed with II via bronchoscopy. The median 24-hour fluid resuscitation requirement was 7.4 mL/kg/% TBSA (IQR 4.6, 12.7). Twenty-two patients (63%) who received hydroxocobalamin developed AKI during the first 72 hours of admission. Twenty-one patients (60%) required CRRT during their hospital stay; 42.8% of patients were started on CRRT during the resuscitation period. The mean admission lactate level was 4.4 ± 2.3 mmol/L. On average, lactate clearance occurred in 34.6 hours; 11 (31.4%) patients did not clear lactate within 72 hours. One patient had a carboxyhemoglobin level greater than 10% on admission. Ten (28.9%) patients died during their hospital stay. Conclusions Most patients who receive hydroxocobalamin after ICU admission developed AKI within the first 72 hours. Further studies on the relationship between the administration of hydroxocobalamin and the development of AKI and in-hospital mortality are warranted. Applicability of Research to Practice The use of hydroxocobalamin may carry an increased risk of AKI. Providers should be aware of this risk when prescribing this medication.
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Serdán Ruiz, David Leonardo, Katterine Kariuxy Vásquez Bone, and Ana Emperatriz Yupa Pallchisaca. "LAS INFECCIONES EN EL TRACTO URINARIO EN LA MUJER EMBARAZADA Y SU INCIDENCIA EN LA MORBILIDAD Y MORTALIDAD DE NEONATOS." Universidad Ciencia y Tecnología 24, no. 106 (2020): 102–8. http://dx.doi.org/10.47460/uct.v24i106.402.

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La infección del tracto urinario de origen bacteriano es una patología frecuente en la mujer embarazada. Constituye un importante factor de riesgo asociado con el desarrollo de sepsis neonatal. La sepsis neonatal es una infección invasiva generalmente acompañada de bacteriemia que se presenta en el neonato en el primer mes de vida. Es una de las causas principales de morbilidad y mortalidad neonatal. El objetivo de esta investigación fue mostrar la relación entre la infección en el tracto urinario en la madre embrazada y la morbilidad y mortalidad del neonato. Se realizó un estudio de casos y controles que incluyó una muestra intencional y no probabilística de 224 pacientes, dividida en dos grupos de interés: 70 casos de neonatos nacidos de mujeres diagnosticadas conla infección y 154 controles de neonatos nacidos de mujeres sanas. Se realizó un análisis bivariado aplicando la prueba Chi cuadrado y estimando el Odds Ratio con apoyo del software OpenEpi, v3. El estudio mostró que los neonatos nacidos de madres con infección del tracto urinario tienen mayor riesgo de desarrollar sepsis neonatal, y sugiere que esta patología, una vez diagnosticada, puede ser tratada con eficacia evitando consecuencias graves para la salud del recién nacido.
 Palabras Clave: Infección, tracto urinario, sepsis neonatal, riesgo en el embarazo.
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 [3]L. Gilstrap, "Medical Complications of pregnancy", Obstretic and ginecology clinics, vol. 28, nº 25, pp. 340-348, 2015.
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 [9]A. Verdecia, N. Antuch , S. Rousseaux y I. Reyes,"Riesgos maternos asociados a sepsis neonatal precoz", Rev Inf Cient, vol. 9, nº 1, p. 74‐83, 2017.
 [10]M. Singer, C. Deutschman, C. Seymour, M. ShankarHari, D. Annane y M. Bauer, "The Third International Consensus Definitions for Sepsis and Septic Shock",JAMA, vol. 315, nº 8, pp. 801-810, 2016.
 [11]G. Fajardo, R. Flores y A. Cárcamo , "Caracterización general de sepsis neonatal temprana", Rev. Fac. Cienc. Méd., vol. 5, nº 2, pp. 28-35, 2017.
 [12]R. Pérez , J. Lona , M. Quiles , M. Verdugo y E.Ascencio , "Sepsis neonatal temprana, incidencia y factores de riesgo asociados en un hospital público del occidente de México", Rev Chilena Infectol, vol. 32, nº 4, pp. 387-392, 2016.
 [13]O. Aríz, A. Clemades, J. Faure, Y. Pérez y N. García, "Sepsis neonatal de inicio precoz en una unidad de cuidados neonatales: gérmenes asociados", Acta Médica del Centro, vol. 13, nº 2, pp. 151-159, 2019.
 [14]G. Samudio, L. Monzón y G. Ortiz, "Sepsis neonatal tardía nosocomial en una unidad de terapia intensiva: agentes etiológicos y localización más frecuente", Rev. chil. infectol , vol. 35, nº 5, pp. 547- 552 , 2018.
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 [16]A. Garaboa, Y. Sarmiento, C. Marquéz y M. Portal, "El recién nacido pretérmino con infección de inicio precoz", Rev Ciencias Médicas , vol. 19, nº 6, pp. 1014-1027 , 2015 .
 [17]T. Zea-Vera, T. Ochoa y Turin C, "Unificando los criterios de sepsis neonatal tardía: propuesta de un algoritmo de vigilancia diagnóstica", Rev Peru Med ExpSalud Publica , vol. 31, nº 2, pp. 358-563 , 2014 .
 [18]I. Belleste, R. Alonso, M. González, A. Campo y R. Amador, "Repercusión de la sepsis neonatal tardía en la morbilidad y mortalidad", Revista Cubana de Obstetricia y Ginecología, vol. 44, nº 1, pp. 1-9, 2018.
 [19]C. Fernandez., "Sepsis de origen precoz", Asturias: Hospital Central de Asturias, 2017.
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8

Thomas, Deborah A., Susan O'Brien, Jeffrey Jorgensen, et al. "Significance of Minimal Residual Disease (MRD) by Multiparameter Flow Cytometry (MFC) In Adults with De Novo Acute Lymphoblastic Leukemia (ALL) After Therapy with the Modified Hyper-CVAD Regimen." Blood 116, no. 21 (2010): 2145. http://dx.doi.org/10.1182/blood.v116.21.2145.2145.

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Abstract Abstract 2145 The hyper-CVAD regimen is an effective frontline program for de novo adult ALL [Kantarjian, JCO 18:547, 2000; Kantarjian, Cancer 101:2788, 2004]. Intensive cycles of hyper-CVAD (fractionated cyclophosphamide, vincristine [VCR], doxorubicin, dexamethasone) alternate with high dose methotrexate (MTX) and cytarabine every 21 days for 8 courses, followed by maintenance therapy with POMP (6-mercaptopurine, MTX, VCR, prednisone) interrupted with early and late intensifications. The regimen was modified in 1999 in order to improve on the results. Induction chemotherapy was administered in a laminar air flow room for pts aged 60 years or older owing to high induction mortality rate (17%). Rituximab 375 mg/m2 (days 1 & 11 of hyper-CVAD, days 1 & 8 of MTX-cytarabine for 8 total doses) was given if CD20 expression was > 20% owing to association with increased propensity for relapse [Thomas D, Blood 113:6330, 2009]. CNS prophylaxis alternated intrathecal MTX day 2 with cytarabine day 7 of the first 3 courses for low CNS risk and first 4 courses for high CNS risk (in the absence of CNS disease). The maintenance phase was extended from 24 to 30 mos with modifications of the early and late intensifications (hyper-CVAD followed by MTX-L-asparaginase mos 6 & 7 and 18 & 19) in order to reduce incidence of late relapses. Newly diagnosed or primary refractory (1 course only) pts with Philadelphia chromosome negative B-lymphoblastic leukemia (n=126) were treated with this modified hyper-CVAD regimen without anthracycline intensification (pts age 30 years or less have been allocated to treatment with the pediatric-inspired augmented Berlin-Frankfurt-Muenster regimen since 2006). Median age was 43 yrs (range, 15–83). CD20 expression was noted in 49%. Overall CR rate of the group was 93%; the rate of MRD negativity by 4- or 6-color MFC (sensitivity of 0.01%) at the time of CR in 95 evaluable pts was 72%. Overall, MRD positivity by MFC at the time of CR was associated with a higher relapse rate (52% versus 21%, p=.01) and lower 3-yr CR duration rates (45% versus 78%, p=.01). The CD20 positive pts (n=57) who were treated with rituximab had a higher rate of MRD negativity by MFC at CR than their CD20 negative counterparts (81% versus 58%, p=.02). MRD positivity by MFC after hyper-CVAD and rituximab was associated with a significantly lower 3-yr CR duration rate (24% versus 82%, p=.002), but survival rates were not statistically different (27% versus 70%) likely due in part to deaths in CR in the older subset of the MRD-negative group. In contrast, for the CD20 negative subset, presence of detectable MRD by MFC at the time of CR was not associated a with lower 3-yr CR duration rate (58% versus 63%). Dectectable MRD by MFC at the time of CR, despite subsequent eradication with consolidation chemotherapy in the majority of patients, predicts for increased risk of disease recurrence. Strategies to improve the MRD negativity rate at the time of CR (e.g., addition of monoclonal antibodies directed at other lymphoblast antigens such as CD22 for the CD20 negative subset and use of the newer anti-CD20 monoclonal antibodies for the CD20 positive subset) may further improve outcome after frontline therapy with the modified hyper-CVAD regimens. Disclosures: Thomas: Novartis: Honoraria; Bristol-Meyer-Squibb: Honoraria; Pfizer:; Amgen: Research Funding. Off Label Use: Imatinib for de novo Philadelphia positive ALL. Dasatinib for de novo Philadelphia positive ALL. Rituximab for CD20 positive ALL and Burkitt leukemia/lymphoma. Nelarabine for de novo T-lymphoblastic leukemia/lymphoma.
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9

Bishr, Amr S., Salma M. Abdelaziz, Ibrahim S. Yahia, Mahmoud A. Yassien, Nadia A. Hassouna, and Khaled M. Aboshanab. "Association of Macrolide Resistance Genotypes and Synergistic Antibiotic Combinations for Combating Macrolide-Resistant MRSA Recovered from Hospitalized Patients." Biology 10, no. 7 (2021): 624. http://dx.doi.org/10.3390/biology10070624.

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Macrolide-resistant methicillin-resistant Staphylococcus aureus (MAC-MRSA) is one of the most clinically relevant pathogens due to its significant ability of resistance acquisition to different antimicrobial agents. This study aimed to evaluate antimicrobial susceptibility and the use of different combinations of azithromycin with other antibiotics for combating MAC resistance. Seventy-two Staphylococci (38.5%) (n = 187), showed resistance to MACs; of these, 53 isolates (73.6%, n = 72) were S. aureus and 19 (26.4%, n = 72) were coagulase-negative staphylococci (CoNS). Out of the 53 S. aureus and 19 CoNS isolates, 38 (71.7%, n = 53) and 9 (47.4%, n = 19) were MRSA and methicillin-resistant CoNS, respectively. The constitutive MACs, lincosamides and streptogramin-B (cMLS) comprised the predominant phenotype among S. aureus isolates (54.7%) and CoNS isolates (78.9%). The PCR analysis showed that the ermC gene was the most prevalent (79.2%), followed by msrA (48.6%), and ermA (31.9%). Azithromycin combinations with either linezolid, ceftriaxone, gentamicin, or cefotaxime provided synergy in 42.1%, 44.7%, 31.6% and 7.9% of the 38 MAC-MRSA isolates, respectively. Statistical analysis showed significant association between certain MAC resistance genotypes and the synergistic effect of certain azithromycin combinations (p value < 0.05). In conclusion, azithromycin combinations with either linezolid, or ceftriaxone showed synergism in most of the MAC-resistant MRSA clinical isolates.
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10

Dagher, Hiba, Anne-Marie Chaftari, Ray Y. Hachem, et al. "356. The Role of Procalcitonin in Antimicrobial Stewardship Among Cancer Patients Admitted with COVID-19." Open Forum Infectious Diseases 8, Supplement_1 (2021): S282. http://dx.doi.org/10.1093/ofid/ofab466.557.

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Abstract Background Procalcitonin (PCT) has been used to guide antimicrobial therapy in bacterial infections. With the wide spread use of empiric use of antibiotics in cancer patients admitted with COVID-19 disease, we aimed to evaluate the role of PCT in decreasing the duration of empiric antimicrobial therapy among cancer patients admitted with COVID-19. Methods We conducted a retrospective study of cancer patients admitted to MD Anderson Cancer Center who had a PCT test done within 72 hours of admission following their COVID-19 diagnosis between March 1, 2020 and June 6, 2021. Patients were divided into 2 groups of PCT < 0.25 ng/mL and PCT >=0.25 ng/mL. We assessed pertinent cultures including blood and respiratory, as well as antibacterial use and duration of empiric antibacterial therapy. Results We identified 544 patients with a median age of 62 years (range, 14-93). There were 312 (57%) patients that had at least one culture obtained from a sterile or infected site within 7 days following admission. None of the patients who had PCT< 0.25 had a positive culture whereas 41/111 (37%) patients with PCT >= 0.25 had at least one positive culture [P< 0.0001]. Among the 373 patients who had a PCT < 0.25, 129 (35%) patients received more than 72 hours of IV antibiotics compared to 87/171 (51%) among patients with PCT >=0.25 [P= 0.0003]. Conclusion These results confirm the correlation between a PCT level greater than 0.25 and a documented bacterial infection. Furthermore, procalcitonin could be useful in enhancing antimicrobial stewardship in cancer patients with COVID-19 by reducing the duration of antimicrobial therapy beyond the initial empiric 72 hours until PCT results become available. Disclosures Natalie J Dailey Garnes, MD, MPH, AlloVir (Other Financial or Material Support, collaborator on research protocol)
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