Citations

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non–muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non–muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody–drug conjugates for metastatic bladder cancer.

Abstract The common side effects of COVID‐19 vaccination were mostly self‐restricted local reactions that quickly resolved. Nevertheless, rare autoimmune hepatitis cases have been reported in some vaccinated with mRNA COVID‐19 vaccines. This article presents a young man who developed fulminant hepatitis a few days after vaccination with the first dose of the AstraZeneca COVID‐19 vaccine. A 35‐year‐old man was admitted to our hospital with generalized weakness, abdominal pain, and jaundice. He received the first dose of the AstraZeneca COVID‐19 vaccine 8 days earlier. He was admitted to the hospital with a chief complaint of abdominal pain. On admission and because of his high D‐dimers, low platelet count, and low Fibrinogen level, vaccine‐induced immune thrombosis thrombocytopenia was suspected, which was ruled out later. Then, after a surge in his liver function tests, decreasing platelet, and abnormal clotting tests, fulminant hepatitis was considered for this patient. Several bacterial, viral, and autoimmune etiologies were then suspected, with all ruled out. Thus, fulminant hepatitis secondary to his AstraZeneca COVID‐19 vaccine was confirmed. Unfortunately, he died 3 days later of disseminated intravascular coagulopathy, after which a liver necropsy was performed, indicating drug/toxin‐induced hepatitis.

Importance National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains unclear. Objective To compare treatment with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) with or without hypofractionated radiation therapy with historical data and establish standards for therapy in borderline resectable PDAC. Design, Setting, and Participants This prospective, multicenter, randomized phase 2 clinical trial conducted from February 2017 to January 2019 among member institutions of National Clinical Trials Network cooperative groups used standardized quality control measures and included 126 patients, of whom 70 (55.6%) were registered to arm 1 (systemic therapy; 54 randomized, 16 following closure of arm 2 at interim analysis) and 56 (44.4%) to arm 2 (systemic therapy and sequential hypofractionated radiotherapy; all randomized before closure). Data were analyzed by the Alliance Statistics and Data Management Center during September 2021. Interventions Arm 1: 8 treatment cycles of mFOLFIRINOX (oxaliplatin, 85 mg/m 2 ; irinotecan, 180 mg/m 2 ; leucovorin, 400 mg/m 2 ; and infusional fluorouracil, 2400 mg/m 2 ) over 46 hours, administered every 2 weeks. Arm 2: 7 treatment cycles of mFOLFIRINOX followed by stereotactic body radiotherapy (33-40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions). Patients without disease progression underwent pancreatectomy, which was followed by 4 cycles of treatment with postoperative FOLFOX6 (oxaliplatin, 85 mg/m 2 ; leucovorin, 400 mg/m 2 ; bolus fluorouracil, 400 mg/m 2 ; and infusional fluorouracil, 2400 mg/m 2 over 46 hours). Main Outcomes and Measures Each treatment arm’s 18-month overall survival (OS) rate was compared with a historical control rate of 50%. A planned interim analysis mandated closure of either arm for which 11 or fewer of the first 30 accrued patients underwent margin-negative (R0) resection. Results Of 126 patients, 62 (49%) were women, and the median (range) age was 64 (37-83) years. Among the first 30 evaluable patients enrolled to each arm, 17 patients in arm 1 (57%) and 10 patients in arm 2 (33%) had undergone R0 resection, leading to closure of arm 2 but continuation to full enrollment in arm 1. The 18-month OS rate of evaluable patients was 66.7% (95% CI, 56.1%-79.4%) in arm 1 and 47.3% (95% CI 35.8%-62.5%) in arm 2. The median OS of evaluable patients in arm 1 and arm 2 was 29.8 (95% CI, 21.1-36.6) months and 17.1 (95% CI, 12.8-24.4) months, respectively. Conclusions and Relevance This randomized clinical trial found that treatment with neoadjuvant mFOLFIRINOX alone was associated with favorable OS in patients with borderline resectable PDAC compared with mFOLFIRINOX treatment plus hypofractionated radiotherapy; thus, mFOLFIRINOX represents a reference regimen in this setting. Trial Registration ClinicalTrials.gov Identifier: NCT02839343

Background and objectives C3 glomerulopathy and idiopathic Ig-associated membranoproliferative GN are kidney diseases characterized by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients develop kidney failure within 10 years. Design, setting, participants, & measurements To improve identification of patients with poor prognosis, we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histologic scoring system, we analyzed 156 native diagnostic kidney biopsies from a retrospective cohort of 123 patients with C3 glomerulopathy and 33 patients with Ig-associated membranoproliferative GN. We used linear regression, survival analysis, and Cox proportional hazards models to assess the relationship between histologic and clinical parameters with outcome. Results Frequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane double contours, and endocapillary hypercellularity. Multivariable analysis showed negative associations between eGFR and crescents, interstitial inflammation, and interstitial fibrosis/tubular atrophy. Proteinuria positively associated with endocapillary hypercellularity and glomerular basement membrane double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at the time of biopsy, cellular/fibrocellular crescents, segmental sclerosis, and interstitial fibrosis/tubular atrophy scores. Conclusions Our detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy scores were significant determinants of deterioration in kidney function.

4020 Background: High grade (G3) GEPNENs are a rare and heterogeneous disease entity for which there is little prospective treatment data. EP chemotherapy is the treatment standard but this may not be appropriate for all G3 GEPNEN pts. CAPTEM has demonstrated activity in G3 GEPNENs and may be a promising alternative. EA2142 aimed to determine if CAPTEM was superior to EP in pts with G3 GEPNENs. Methods: This was a multicenter, randomized (1:1) phase II trial for pts with a locally advanced and unresectable or metastatic well differentiated G3 neuroendocrine tumor (NET) or a poorly differentiated, non-small cell G3 neuroendocrine carcinoma (NEC) of suspected gastrointestinal origin and an ECOG PS of 0-2. Pathology must have demonstrated a Ki-67 of 20-100% or at least 10 mitoses/10 high powered field. Pts were randomized to receive capecitabine 750 mg/m2 orally every 12 hours on days 1-14 and temozolomide 200 mg/m2 orally once daily on days 10-14 of a 28-day treatment cycle (Arm A) or etoposide 100 mg/m2 daily on days 1-3 with either cisplatin 25 mg/m2 daily on days 1-3 or carboplatin AUC 5 on day 1 of a 21-day treatment cycle (Arm B). Restaging scans were performed every 8 weeks and toxicity monitored per CTCAEv4. Final statistical plan was to accrue 80 pts to detect a 67% improvement in progression free survival (PFS) (primary endpoint) with CAPTEM as compared to EP, 80% power and one-sided significance level of 0.10. A planned interim analysis for efficacy and futility was conducted. Results: A total of 67 pts were enrolled (Arm A, n=32; Arm B, n=35). Male 58%, African American 4%, Asian 3%. Mean age 61. Among 63 eligible pts, primary tumor site pancreatic 56%, non-pancreatic 43%. Poorly differentiated 57%, well differentiated 33%, unknown 10%. Mean Ki-67 48% (Arm A), 60% (Arm B). The study was closed prior to full accrual due to futility at 57.7% information time. In the interim analysis, among 62 eligible pts, PFS, overall survival and response rate with CAPTEM were 2.43 months (mos) (95% CI 2.04, 7.72), 12.6 mos, 9% respectively vs 5.36 mos (95% CI 2.14, 7.23), 13.6 mos and 10% with EP. Toxicity was evaluable in 57 pts with Grade (G) 3/4 events occurring in 29% of pts on Arm A, 66% of pts on Arm B. G3/4 events occurring in more than 5% of pts on Arm A—febrile neutropenia (n=2); abdominal pain (n=2); diarrhea (n=2); nausea (n=2); neutropenia (n=2); dehydration (n=2) and on Arm B—anemia (n=8); febrile neutropenia (n=2); fatigue (n=2); lymphopenia (n=2); neutropenia (n=12); thrombocytopenia (n=4); leukopenia (n=6). There was one G5 event on Arm A due to sepsis. Conclusions: CAPTEM does not appear to be superior to EP chemotherapy as front-line treatment for pts with G3 NENs but does demonstrate a more favorable toxicity profile. Studies assessing G3 NET independently of G3 NEC are needed. Clinical trial information: NCT02595424.

Human monkeypox is a zoonotic Orthopoxvirus resembling smallpox in clinical course, making it difficult to distinguish it from smallpox and varicella. Laboratory diagnostics are critical components of illness identification and surveillance, and novel tests are required for more precise and quick diagnosis. The majority of human infections occur in Central Africa, where monitoring in remote regions with little infrastructure is challenging but may be performed using evidence-based methods and teaching materials that educate public health personnel on the fundamental principles of this infection. New medications and vaccinations showed promising results for the treatment and prevention of the disease, but more studies are required to show their efficacy in the actual endemic settings. Thus, more studies are needed on the virus's epidemiology, ecology, and biology in endemic locations to better understand and prevent human infections. This review discussed the etiology, epidemiology, and clinical course of the monkeypox and indicated diagnostic and treatment approaches for this disease.

AbstractThe coronavirus disease 2019 (COVID‐19) has various presentations, of which immune dysregulation or the so‐called cytokine storm syndrome (COVID‐CSS) is prominent. Even though cytokines are vital regulators of body immunoinflammatory responses, their exaggerated release can be harmful. This hyperinflammatory response is more commonly observed during severe COVID‐19 infections, caused by the excessive release of pro‐inflammatory cytokines, such as interleukin‐1 (IL‐1), IL‐6, IL‐8, tumour necrosis factor, granulocyte‐macrophage colony‐stimulating factor, and interferon‐gamma, making their blockers and antagonists of great interest as therapeutic options in this condition. Thus, the pathophysiology of excessive cytokine secretion is outlined, and their most important blockers and antagonists are discussed, mainly focussing on tocilizumab, an interleukin‐6 receptor blocker approved to treat severe COVID‐19 infections.

Remdesivir has appeared to be the most effective medication against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is broadly administered to the coronavirus disease 2019 (COVID-19) patients around the world. Remdesivir is an RNA polymerase inhibitor with a broad spectrum of antiviral activities against RNA viruses in in-vitro and in-vivo models of SARS-CoV, the Middle East respiratory syndrome (MERS), and SARS-CoV-2. Remdesivir is the first Food and Drug Administration (FDA) approved anti-SARS-CoV-2 treatment for adult and pediatric patients and has been used intravenously for patients requiring hospitalization for COVID-19. However, questions have been raised about the value of remdesivir in treating COVID-19, and governing bodies worldwide have been hesitant to approve this medication. Nevertheless, in the context of the public health emergency and the urgent need for effective treatments for patients with COVID-19, remdesivir has been approved by several authorities worldwide. Here, we discuss characteristics and applications of remdesivir, and various challenging studies with different outcomes about its efficacy are also reviewed.

Objectives: The current study aimed to compare the efficacy of the two different prophylactic antibiotic regimens (2-days vs. 7-days) in preventing surgical site infection in coronary artery bypass grafting (CABG). Methods : Patients undergoing CABG were included in this randomized, double-blind, placebo-controlled trial. From 2016 to 2017, 370 cases were allocated to one of two groups. The groups received prophylactic antibiotic therapy for either 2-days or 7-days. All CABG patients were followed for days for surgical site infections. Two of the patients died after surgery, and 3 patients did not show up during the three-month follow-up evaluation and thus did not meet the study criteria. Results: Of the remaining 365 patients who participated in the full study, 198 (54.2%) were male, and 167 (45.7%) were female patients. The mean age of these cases was 58.64± 11.4. Of the 365 study participants who received prophylactic antibiotics prior to surgery, 16 patients developed surgical site infections (legs and sternum). Among these 16 patients, nine cases belong to the 7-days prophylactic antibiotic therapy group (2.4%), and seven cases belong to the 2-day prophylactic antibiotic therapy group (1.9%) (P=0.771). Conclusion: Comparison of two 2-day and 7-day prophylactic antibiotic regimens showed no significant difference in the incidence of post-surgical infection in the two groups.