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.

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.

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.