Improved survival for dose-intensive chemotherapy in primary mediastinal B-cell lymphoma: a systematic review and meta-analysis of 4,068 patients.

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct clinicopathologic entity. Currently, there is a paucity of randomized prospective data to inform on optimal front-line chemoimmunotherapy (CIT) and use of consolidative mediastinal radiation (RT). To assess if distinct CIT approaches are associated with disparate survival outcomes, we performed a systematic review and meta-analysis comparing dose-intensive (DI-CIT) versus standard CIT for the front-line treatment of PMBCL. Standard approach (S-CIT) was defined as R-CHOP-21/CHOP-21, with or without RT. DI-CIT were defined as regimens with increased frequency, dose, and/or number of systemic agents. We reviewed data on 4,068 patients (2,517 DI-CIT; 1,551 S-CIT) with a new diagnosis of PMBCL. Overall survival for DI-CIT patients was 88% (95% CI: 85-90) compared to 80% for the S-CIT cohort (95% CI: 74-85). Meta-regression revealed an 8% overall survival (OS) benefit for the DI-CIT group (P<0.01). Survival benefit was maintained when analyzing rituximab only regimens; OS was 91% (95% CI: 89-93) for the rituximab-DI-CIT arm compared to 86% (95% CI: 82-89) for the R-CHOP-21 arm (P=0.03). Importantly, 55% (95% CI: 43-65) of the S-CIT group received RT compared to 22% (95% CI: 15-31) of DI-CIT patients (meta-regression P<0.01). To our knowledge, this is the largest meta-analysis reporting efficacy outcomes for the front-line treatment of PMBCL. DI-CIT demonstrates a survival benefit, with significantly less radiation exposure, curtailing long-term toxicities associated with radiotherapy. As we await results of randomized prospective trials, our study supports the use of dose-intensive chemoimmunotherapy for the treatment of PMBCL.

Antibiotic prophylaxis for onabotulinum toxin A injections: systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: To our knowledge, there are no evidence-based recommendations regarding the optimal prophylactic antibiotic regimen for intradetrusor onabotulinum toxin type A (BTX) injections. This systematic review and meta-analysis was aimed at investigating the optimal prophylactic antibiotic regimen to decrease urinary tract infection (UTI) in patients undergoing BTX for overactive bladder syndrome (OAB). METHODS: A systematic search of MEDLINE, Embase, CINAHL, and Web of Science was conducted from inception through 30 June 2022. All randomized controlled trials and prospective trials with > 20 subjects undergoing BTX injections for OAB in adults that described prophylactic antibiotic regimens were included. Meta-analysis performed to assess UTI rates in patients with idiopathic OAB using the inverse variance method for pooling. RESULTS: A total of 27 studies (9 randomized controlled trials, 18 prospective) were included, representing 2,100 patients (69% women) with 19 studies of idiopathic OAB patients only, 6 of neurogenic only, and 2 including both. No studies directly compared antibiotic regimens for the prevention of UTI. Included studies favor the use of antibiotics in patients with idiopathic OAB and favor continuing antibiotics for 2-3 days after the procedure for prevention of UTI. Given the heterogeneity of the data, direct comparisons of antibiotic type or duration could not be performed. Meta-analysis found a 10% UTI rate at 4 weeks and 15% at 12 weeks post-injection. CONCLUSIONS: Although there are insufficient data to support the use of a specific antibiotic regimen, available studies favor the use of prophylactic antibiotics for 2-3 days in idiopathic OAB patients undergoing BTX injection. Future trials are needed to determine the optimal regimens to prevent UTI in patients undergoing BTX for OAB.

The Effect of Early Severe Hyperoxia in Adults Intubated in the Prehosptial Setting or Emergency Department: A Scoping Review.

BACKGROUND: The detrimental effects of hyperoxia exposure have been well-described in patients admitted to intensive care units. However, data evaluating the effects of short-term, early hyperoxia exposure in patients intubated in the prehospital setting or emergency department (ED) have not been systematically reviewed. OBJECTIVE: Our aim was to quantify and describe the existing literature examining the clinical outcomes in ED patients exposed to hyperoxia within the first 24 h of mechanical ventilation. METHODS: This review was performed in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews. Two rounds of review using Rayyan QCRI software were performed for title and abstract screening and full-text search. Of the 2739 articles, 27 articles were retrieved after initial screening, of which 5 articles were excluded during the full-text screening, leaving 22 articles for final review and data extraction. RESULTS: Of 22 selected publications, 9 described patients with traumatic brain injury, 6 with cardiac arrest, 3 with multisystem trauma, 1 with stroke, 2 with septic shock, and 1 was heterogeneous. Three studies were randomized controlled trials. The available data have widely heterogeneous definitions of hyperoxia exposure, outcomes, and included populations, limiting conclusions. CONCLUSIONS: There is a paucity of data that examined the effects of severe hyperoxia exposure in the acute, post-intubation phase of the prehospital and ED settings. Further research with standardized definitions is needed to provide more detailed guidance regarding early oxygen titration in intubated patients.

Immunotherapy Use Prior to Liver Transplant in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide, and its incidence has increased rapidly in the United States over the past two decades. Liver transplant is considered curative, but is not always possible, and pre-transplant immunotherapy is of great interest as a modality for downstaging the tumor burden. We present a review of the literature on pre-liver transplant immunotherapy use in patients with HCC. Our literature search queried publications in Ovid MEDLINE, Ovid Embase, and Web of Science, and ultimately identified 24 original research publications to be included for analysis. We found that the role of PD-1 and PD-L1 in risk stratification for rejection is of special interest to researchers, and ongoing randomized clinical trials PLENTY and Dulect 2020-1 will provide insight into the role of PD-1 and PD-L1 in liver transplant management in the future. This literature search and the resulting review represents the most thorough collection, analysis, and presentation of the literature on the subject to date.

Effect of Vitamin D on Experimental Autoimmune Neuroinflammation Is Dependent on Haplotypes Comprising Naturally Occurring Allelic Variants of CIITA (Mhc2ta).

An increasing body of evidence associates low vitamin D levels with increased risk of multiple sclerosis (MS), suggesting the possibility of a gene-environment interaction for this environmental factor in MS pathogenesis. Moreover, it has been shown that vitamin D downregulates major histocompatibility complex (MHC) class II expression in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We here report about the impact of a dietary vitamin D supplementation on EAE in the rat strains having functionally relevant allelic variations in the CIITA (Mhc2ta) gene, a master regulator of MHC class II expression. Full length myelin oligodendrocyte glycoprotein (MOG)-EAE was induced in DA.PVGav1-Vra4 congenic rats harboring the Vra4 locus from PVG strain in the EAE- susceptible DA background, and compared to the parental strains. The congenic rats fed with either vitamin D supplemented, deprived or regular diet developed an intermediate clinical EAE phenotype, in contrast to DA and PVG strains. Immunopathological studies revealed vitamin D dose-dependent effect on demyelination and inflammatory infiltration of the central nervous system (CNS), expression of MHC class II and CIITA, as well as downregulation of a range of pro-inflammatory genes. Taken together, our findings demonstrate an impact of vitamin D on the target tissue pathology and peripheral immune response during EAE in DA.PVGav1-Vra4 congenic strain. Thereby, our data provide evidence of a modulatory effect of vitamin D in context of genetic variances in the Vra4 locus/Mhc2ta gene in MS-like neuroinflammation, with potential relevance for the human demyelinating disease.