Academic literature on the topic 'Mark 4:35-41'

Background: Emergency medicine in Romania has developed fast since inception. The need for faster diagnostic capabilities due to the high workload pre- and in-hospital made point-of-care ultrasound (POCUS) a logical next step. The advantages of POCUS are well known, but implementation presents challenges. Our goal was to study how a straightforward method of implementation would work locally. Methods: Two prospective observational studies were conducted at 6 months (prehospital) and 4 months (in-hospital). The protocol used was extended focused assessment sonography in trauma (eFAST), and the shock index (SI) was used to stratify patients. Voluntary sampling was conducted by emergency physicians. The primary outcomes were patient numbers, type of case use, results, and accuracy. Results: The prehospital study registered 34 patients: 41% traumas, 35% cardiac arrest, 18% shock, and 6% acute respiratory distress. The in-hospital study patients were 78: 36% traumas, 6% cardiac arrests, 41% shock, and 17% acute respiratory distress. A total of 88.5% of the cases were confirmed with definitive imagistic findings. Conclusion: The studies mark an increase in POCUS usage and use in complicated cases. Providing supervision and feedback into clinical practice resulted in a further increase in POCUS usage, the second study having an 88.5% accuracy when compared to the final diagnostic proving the increased efficiency of a longitudinal training approach.

Abstract Background: The anti-TIGIT antibody vibo in combination with pembro was well tolerated across all doses in the dose-escalation phase of the ongoing phase 1 study in pts with advanced solid tumors (NCT02964013); promising antitumor activity of vibo + pembro was observed in anti-PD-1/PD-L1-naive NSCLC. We present initial results of the dose-expansion phase in pts with advanced cervical cancer naive to PD-1/PD-L1 inhibitors. Methods: Pts with histologically confirmed, locally advanced, or metastatic cervical cancer who failed prior standard-of-care chemotherapy or who experienced early progression on definitive chemoradiation and were naive to PD-1/PD-L1 inhibitors were randomly assigned 1:1 to receive 1 of 2 doses of vibo (200 or 700 mg) + pembro (200 mg) Q3W for ≤35 cycles (~2 y) or until PD, toxicity, or pt withdrawal. Primary end points were safety and tolerability. Secondary and exploratory end points included ORR, DOR, and PFS by investigator review per RECIST v1.1. Results: Median age of the 80 pts with cervical cancer was 49 y; 58% had an ECOG PS of 1; 53% received ≥2 prior lines of therapy; and 61% had PD-L1-positive tumors. 41 pts received vibo 200 mg, and 39 received vibo 700 mg. Median follow-up was 12 mo (range, 5-26). Treatment-related AEs (TRAEs) occurred in 27 pts in each treatment group (66%, vibo 200 mg; 69%, vibo 700 mg). The most frequent TRAEs (≥15%) were rash (22%), increased lipase (17%), and pruritus (17%) with vibo 200 mg + pembro and pruritus (28%), pyrexia (21%), rash (15%), and fatigue (15%) with vibo 700 mg + pembro. Grade 3 or 4 TRAEs occurred in 29% (vibo 200 mg + pembro) and 18% (vibo 700 mg + pembro). No deaths due to TRAEs were reported. Efficacy is reported in the Table. Conclusions: Vibo + pembro was safe in pts with advanced cervical cancer. Antitumor activity was comparable between the 2 doses of vibo studied and responses were observed irrespective of PD-L1 status. Based on these data, the RP2D for vibo remains 200 mg Q3W. Efficacy By Treatment Group By PD-L1 Statusa Vibo 200 mg + Pembro n = 41 Vibo 700 mg + Pembro n = 39 PD-L1-positive n = 49 PD-L1-negative n = 21 Confirmed ORR, % (95% CI) 15 (6-29) 23 (11-39) 20 (10-34) 14 (3-36) CR, n (%) 2 (5) 5 (13) 6 (12) 1 (5) PR, n (%) 4 (10) 4 (10) 4 (8) 2 (10) SD, n (%) 12 (29) 7 (18) 14 (29) 3 (14) PD, n (%) 18 (44) 19 (49) 20 (41) 12 (57) Median DOR, months (range)b Not reached (10 to 31+) Not reached (4+ to 35+) Not reached (4+ to 35+) Not reached (21 to 27+) Median PFS, months (95% CI) 2 (2-4) 2 (2-4) 4 (2-4) 2 (1-4) CR, complete response; DOR, duration of response; PD, progressive disease; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SD, stable disease. aPD-L1 status was unknown in 10 patients; data were pooled across treatment groups. PD-L1 positivity was defined as combined positive score (CPS) ≥1 or when CPS was missing, as tumor proportion score ≥1% or mononuclear immune cell density score ≥2. b“+” indicates no PD present at the time of the last disease assessment. Citation Format: Ronnie Shapira-Frommer, Ruth Perets, Mark Voskoboynik, Kathryn Mileham, Adnan Nagrial, Brian Stein, Vincent Chung, Martin Gutierrez, Diana Chen, Tanya Keenan, Mohini Rajasagi, Jane Healy, Sun Young Rha. Safety and efficacy of vibostolimab (vibo) plus pembrolizumab (pembro) in patients (pts) with cervical cancer naive to PD-1/PD-L1 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT508.

Abstract Despite tremendous advancement in the understanding and manipulation of immune checkpoint molecules in immunotherapeutic design, there are still vast limitations in treatment efficacy. Immunotherapy manipulates the immune checkpoint blockade (ICB), blocking negative regulators of the immune system-preventing tumor immune evasion. Combination therapy enhances the mechanistic actions of each individual component, enhancing tumoricidal behavior. Thermal ablation to induce cancer cell death as a therapeutic adjuvant is an understudied area. B16-F10 melanoma cells were grown at 37°C or 41°C. B16-F10 cells grown at 41°C decreased cell migration by 70% in 24 hours. B16-F10 cell proliferation was decreased at 41°C by 62% at 48 hours and 94% at 72 hours. Protein expression profiles were evaluated under hyperthermic conditions in vitro. Expression of pERK and ERK decreased by 86% and 50% and Caspase-3 increased by 31% at 41°C. Cell stress can induce death pathways and the heat shock protein response simultaneously, therefore we investigated inducible Hsp70 expression. Hsp70 expression was undetectable at 37°C and 188% at 41°C. Cytokine analysis of conditioned media showed that at 41°C, TNF-α expression was increased and IL-4 expression was decreased, suggesting a proinflammatory shift in cytokine profiles at higher temperatures. In support of our data, hyperthermia-induced TNF-α apoptotic responses have been reported. Programmed cell death ligand (PD-L1) is expressed by tumors to suppress immune cells and induce tolerogenic phenotypes within the tumor microenvironment. We observed that hyperthermic potentiation decreased the expression of this checkpoint molecule in B16-F10 by 35%. Therefore, we hypothesize that hyperthermia modulates the tumor microenvironment to enhance their responsiveness to checkpoint immunotherapies. Based on these promising in vitro results, we plan to further explore the clinical aspect of our findings through a translation in vivo. B16-F10 cells will be implanted onto C57BL/6 mice and treated with infrared radiation in combination with either anti-PD-L1, anti-PD-1, or IL-15. Citation Format: Nicole DeSouza, Danielle Quaranto, Kaci Kopec, Jan Geliebter, Raj K. Tiwari, Mark D. Hurwitz. Intratumoral manipulation of melanoma using novel hyperthermic treatment to enhance anti-PD-L1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3226.

Background: Hanging is caused by suspension of the body by a ligature encircling the neck. The person may use any article readily available for this purpose, like a rope, saree, belt, bed sheet etc. Most times, Ligature mark and material may be the only evidence available in deaths due to either hanging or strangulation. Their thorough examination and analysis is extremely helpful in differentiation and provide vital medicolegal information. Material and Method: Present study was conducted among the dead bodies brought to the mortuary of Swaroop Rani Nehru hospital MLN Medical College Allahabad. Out of 2654 cases autopsied during the study period from 01/05/2016 to 30/4/2017; 184 cases (6.93%) were caused by violent asphyxial death. Out of that 120 (65.2%) cases including hanging (94) and strangulation (26) were taken for study. Results and Conclusion: The young adults of the age group of 21-40 years contributed for majority of cases with 66(55%) of cases of hanging and 16(13.3%) of cases of strangulation. The position of knot was seen on the right side in 42(35%) cases. Duppatta was most commonly used ligature material 41(34.16%). The most common external finding was cyanosis seen in 84 (70%) and 26 (21.66%) cases of hanging and strangulation, respectively. Present study provides vital information for the Doctors, Police and concerned authorities in investigating cases of Hanging and strangulation.