Toxicities of CAR T-cell therapy: a review of current literature.

The chimeric antigen receptor (CAR) design, first invented by Zelig Eshhar, paved the way for the use of genetically modified T-cells in targeted therapy against cancer cells. Since then, it has gone through many generations, especially with the integration of co-stimulation in the second and third-generation CARs. However, it also mounts a hyperactive immune response named as cytokine release syndrome with the release of several cytokines eventually resulting in multiple end-organ toxicities. The severity of cytokine release syndrome depends upon certain factors such as the tumor burden, choice of co-stimulation, and degree of lymphodepletion, and can manifest as pulmonary edema, vascular leak, renal dysfunction, cardiac problems, hepatic failure, and coagulopathy. Many grading criteria have been used to define these clinical manifestations but they lack harmonization. Neurotoxicity has also been significantly associated with CAR T-cell therapy but it has not been studied much in previous literature. This review aims to provide a comprehensive account of the clinical manifestations, diagnosis, management, and treatment of CAR T-cell associated neurotoxicity.

How well does the virtual format of oncology multidisciplinary team meetings work? An assessment of participants' perspectives and limitations: A scoping review.

BACKGROUND: Virtual multidisciplinary team meetings (VMDTM) provide a standard of care that is not limited by physical distance or social restrictions. And so, when the COVID-19 pandemic imposed irrefutable social restrictions and made in-person meetings impossible, many hospitals switched to the VMDTMs. Although the pandemic might have highlighted the ease of VMDTMs, these virtual meetings have existed over the past decade, albeit less in importance. Despite their recent importance, no review has previously assessed the feasibility of VMDTMs through the eyes of the participants, the barriers participants face, nor their comparison with the in-person format. We undertook this scoping review to map existing literature and assess the perspectives of VMDTM participants. MATERIAL AND METHODS: We searched MEDLINE, Embase, CINAHL, and Google Scholar from inception till July 1st, 2023 to select studies that evaluated the perspectives of participants of VMDTMs regarding the core components that make up a VMDMT. Four authors, independently, extracted data from all included studies. Two authors separated data into major themes and sub-themes. RESULTS: We identified six core, intrinsic aspects of a VMDTM that are essential to its structure: (1) organization, (2) case discussion and decision-making, (3) teamwork and communication, (4) training and education, (5) technology, and (6) patient-related aspect. VMDTMs have a high overall satisfaction rating amongst participants. The preference, however, is for a hybrid model of multidisciplinary teams. VMDTMs offer support to isolated physicians, help address complex cases, and offer information that may not be available elsewhere. The periodical nature of VMDTMs is appropriate for their consideration as CMEs. Adequate technology is paramount to the sustenance of the format. CONCLUSION: VMDTMs are efficient and offer a multidisciplinary consensus without geographical limitations. Despite certain technical and social limitations, VMDTM participants are highly satisfied with the format, although the preference lies with a hybrid model.

Hepatic encephalopathy with proton pump inhibitor use in post tips patients: a systematic review and meta-analysis.

INTRODUCTION: Hepatic encephalopathy (HE) after Trans-jugular intrahepatic portosystemic shunt (TIPS) is a common clinical problem. According to recent studies, Proton pump inhibitor (PPI) use can serve as an independent risk factor for HE. We performed a systematic review and meta-analysis to analyze the association between HE with PPI use versus without PPI use in patients undergoing TIPS. EVIDENCE ACQUISITION: We conducted a comprehensive literature search from inception through February 15th, 2022 on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases. Odds ratio (OR) was calculated when comparing dichotomous variables of patients with HE vs no HE in PPI use versus no PPI use in post TIPS patients. A 95% confidence interval (CI) and P values (<0.05 considered significant) were also generated. EVIDENCE SYNTHESIS: The search strategy yielded a total of 27 articles. We finalized four studies with a total of 825 patients. There was statistically significant difference in TIPS patients with HE in PPI users versus non-PPI users (OR 3.39 [1.79-6.43], P<0.01, I2=55.5%). Pooled mean average days to hospitalization was 215.2 days to hospitalization for hepatic encephalopathy in non-PPI users compared to 139.5 days in PPI users. CONCLUSIONS: Our study determines that there is a higher risk of post-TIPS HE in patients on PPI therapy vs. patients not receiving PPI therapy. We recommend using PPIs at a lower tolerable dose where necessary. Larger studies are needed to draw stronger conclusions.

Transesophageal echocardiography-associated gastrointestinal injuries: systematic review and pooled rates of gastrointestinal injuries.

Upper gastrointestinal (GI) injuries are associated with transesophageal echocardiography (TEE) complications. We reviewed rates and various types of complications with GI injuries. A comprehensive literature search using five databases was conducted. Pooled rates were calculated for overall injuries, pooled GI complications, lacerations, and perforations with a 95% confidence interval (CI). A total of 26 studies involving 55,319 patients met inclusion criteria. The overall rate of adverse events was 0.51% (95% CI 0.3% to 0.7%). Bleeding was the most commonly reported adverse event, followed by dysphagia and lacerations. The highest rate of adverse events was observed in liver transplant patients (1.35%), followed by critically ill patients in the intensive care unit (1.1%), hospitalized patients (1.1%), patients undergoing intraoperative TEE (0.7%), and those undergoing cardiac procedures (0.67%). The pooled complication rate for bleeding was 0.17% (95% CI 0.1% to 0.3%), while odynophagia/dysphagia had a rate of 0.27% (95% CI -0.1% to 0.5%) and lacerations had a rate of 0.12% (95% CI -0.1% to 0.5%). A subgroup analysis comparing variceal and nonvariceal cohorts from three studies showed no significant difference in bleeding rates. Our study findings showed a low risk of esophageal injury in patients undergoing TEE.

Comparing adalimumab and infliximab in the prevention of postoperative recurrence of Crohn's disease: a systematic review and meta-analysis.

Background: Crohn's disease is a relapsing disease that often requires operative management. Prevention of postoperative recurrence (POR) is critical to maintain remissions. Biologic agents have proven to be most successful in remission maintenance. We made a direct head-to-head comparison of the 2 anti-tumor necrosis factor agents, infliximab (IFX) and adalimumab (ADA), to compare endoscopic and clinical POR of Crohn's disease. Methods: We conducted a comprehensive literature search in 7 databases, including Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science Core Collection, KCI-Korean Journal Index, SciELO, and Global Index Medicus. Odds ratios (OR) were calculated with 95% confidence intervals (CI) and P-values (<0.05 considered significant). We evaluated the total rates of endoscopic recurrence, endoscopic recurrence at 1 year, and clinical recurrence rates of IFX and ADA in a direct head-to-head comparison. Results: The search strategy yielded a total of 393 articles. Three studies with a total of 268 participants were included. Our meta-analysis showed no statistically significant difference in total endoscopic recurrence rate between ADA and IFX (27.1% vs. 32.3%, OR 0.696, 95%CI 0.403-1.201; P=0.193; I 2=0%). Nor was there any significant difference between the drugs in endoscopic recurrence rate at 1 year (OR 0.799, 95%CI 0.329-1.940; P=0.620) or clinical recurrence rate (OR 0.477, 95%CI 0.477-1.712; P=0.755). Conclusions: ADA and IFX show comparable efficacy in preventing POR endoscopically and clinically. The clinical decision should be based on cost, side-effects, tolerability, and patient preferences. Additional studies, particularly randomized controlled trials, are needed to determine generalizability.

An assessment of knowledge, attitude, and practice regarding organ donation among students and physicians.

OBJECTIVE: To assess the knowledge, attitude and practice of students and physicians regarding tissue and organ donation at a teaching hospital. Methods: The cross-sectional study was conducted at the Dow University of Health Sciences, Karachi, in 2019, and comprised physicians and students of ether gender. Data was collected using a 43-item self-administered questionnaire. Dichotomous questions were scored as 1 or 0, while multiple-option questions were scored as 2, 1 or 0. Data was analysed using SPSS 25. RESULTS: Of the 859 subjects, 761(88.6%) were students with a mean age of 20.3±1.5 years and 98(11.4%) were physicians with a mean age of 30.6±9.4. Among the students, 630(82.8%) were medical students, while 131(17.2%) were dental. The largest group among the students was of those in the second year of their studies 271(35.6%). Besides, 531(69.8%) and 64(65.3%) physicians were females. Compared to males, female students reported better mean scores in terms of attitude, while higher practice scores were obtained by both male students and physicians (p=0.021). Muslim subjects scored comparatively lower in knowledge, attitude and practice terms than non-Muslims (p<0.05). CONCLUSIONS: There were high knowledge and attitude scores, while scores reflecting practice were low. Effective measures should be taken to encourage medical professionals to donate organs and promote organ donation.

Role of prophylactic hemoclip placement in prevention of delayed post-polypectomy bleeding for large colon polyps: a meta-analysis of randomized controlled trials.

BACKGROUND: Polypectomy is a widely used and effective procedure to treat precancerous polyps. Delayed post-polypectomy bleeding (DPPB), a common complication of polypectomy, may diminish the utility of this procedure. Previous data on the efficacy of hemoclips has been conflicting, therefore we aimed to collectively evaluate and analyze the data to reach a definitive conclusion on the efficacy of using hemoclips to prevent incidences of DPPB in patients with large polyps (≥10 mm). METHODS: We identified a total of 261 studies based on our previously defined search strategy. After screening, we included 6 randomized controlled trials. A meta-analysis was performed comparing the use of prophylactic application of hemoclips to a standard group without prophylactic clip placement for large polyps. RESULTS: We found a statistically significant reduction in the incidence of DPPB when using hemoclips for large polyps. The overall incidence of DPPB was lower in the hemoclip group compared to the standard group for all large polyps ≥10 mm (relative risk 0.51, 95% confidence interval 0.35-0.75; P=0.01; I 2=0%). CONCLUSIONS: The use of hemoclips in achieving hemostasis for large polyps has a beneficial effect and appears to prevent DPPB. This reinforces the routine clinical practice of using hemoclips in polypectomy procedures.