Search

ImportanceThe BCG vaccine—used worldwide to prevent tuberculosis—confers multiple nonspecific beneficial effects, and intravesical BCG vaccine is currently the recommended treatment for non–muscle-invasive bladder cancer (NMIBC). Moreover, BCG vaccine has been hypothesized to reduce the risk of Alzheimer disease and related dementias (ADRD), but previous studies have been limited by sample size, study design, or analyses.ObjectiveTo evaluate whether intravesical BCG vaccine exposure is associated with a decreased incidence of ADRD in a cohort of patients with NMIBC while accounting for death as a competing event.Design, Setting, and ParticipantsThis cohort study was performed in patients aged 50 years or older initially diagnosed with NMIBC between May 28, 1987, and May 6, 2021, treated within the Mass General Brigham health care system. The study included a 15-year follow-up of individuals (BCG vaccine treated or controls) whose condition did not clinically progress to muscle-invasive cancer within 8 weeks and did not have an ADRD diagnosis within the first year after the NMIBC diagnosis. Data analysis was conducted from April 18, 2021, to March 28, 2023.Main Outcomes and MeasuresThe main outcome was time to ADRD onset identified using diagnosis codes and medications. Cause-specific hazard ratios (HRs) were estimated using Cox proportional hazards regression after adjusting for confounders (age, sex, and Charlson Comorbidity Index) using inverse probability scores weighting.ResultsIn this cohort study including 6467 individuals initially diagnosed with NMIBC between 1987 and 2021, 3388 patients underwent BCG vaccine treatment (mean [SD] age, 69.89 [9.28] years; 2605 [76.9%] men) and 3079 served as controls (mean [SD] age, 70.73 [10.00] years; 2176 [70.7%] men). Treatment with BCG vaccine was associated with a lower rate of ADRD (HR, 0.80; 95% CI, 0.69-0.99), with an even lower rate of ADRD in patients aged 70 years or older at the time of BCG vaccine treatment (HR, 0.74; 95% CI, 0.60-0.91). In competing risks analysis, BCG vaccine was associated with a lower risk of ADRD (5-year risk difference, −0.011; 95% CI, −0.019 to −0.003) and a decreased risk of death in patients without an earlier diagnosis of ADRD (5-year risk difference, −0.056; 95% CI, −0.075 to −0.037).Conclusions and RelevanceIn this study, BCG vaccine was associated with a significantly lower rate and risk of ADRD in a cohort of patients with bladder cancer when accounting for death as a competing event. However, the risk differences varied with time.

To characterize pulmonary toxicities associated with the use of novel immune checkpoint inhibitors Adverse event reports from immune checkpoint inhibitors targeting PD-1/L1 and CTLA-4 were captured from the W.H.O pharmacovigilance database (VigiBase) up until Dec. 31st 2019 and were analyzed to evaluate for measures of association between the use of immune checkpoint inhibitors and pulmonary toxicities. Disproportionality analysis using both frequentist and Bayesian approaches were used to detect signals between pulmonary immune-related adverse events and the use of these agents. A total of 9202 adverse pulmonary immune checkpoint inhibitor-related events were captured up until 2019. Adverse pulmonary events were compromised of 1305 airway, 18 alveolar, 5491 interstitial, 898 pleural, 560 vascular and 939 non-specific pulmonary events. We found a common association between all immune checkpoint inhibitors studied and pneumonitis, interstitial lung disease, pulmonary embolism and respiratory failure. We also noted other associations between immune checkpoint inhibitors, however not as uniformly across agents. Most of these immune-related adverse drug reactions were noted to be severe and accounted for a significant source of mortality in the reported cases. Immune checkpoint inhibitors are associated with a spectrum of inflammatory pulmonary toxicities. The breadth of pulmonary complications and prevalence may be underappreciated with the use of these agents.

INTRODUCTION AND OBJECTIVE:Tobacco use has been shown to be an independent risk factor for postoperative morbidity following a variety of major surgeries. While tobacco use is both a risk factor fo...

INTRODUCTION AND OBJECTIVE:Acute urinary retention due to benign prostatic hyperplasia (BPH) is an indication for surgery, yet many patients experience delays to surgical intervention. We assess th...

The impact of anemia in postoperative complications following radical cystectomy (RC) is not completely elucidated and its association with direct hospital costs has not been characterized in depth. Our goal is to determine the association between anemia, 90-day surgical complications and the expenditure attributed to preoperative anemia in patients undergoing RC.We captured all patients who underwent RC between 2003 and 2017 using the Premier Hospital Database (Premier Inc, Charlotte, NC). Patient, hospital and surgical characteristics were evaluated. Anemia was defined by a corresponding diagnostic code that was present on admission prior to RC. Unadjusted patients' demographic characteristics with and without anemia, hospital and surgeon characteristics were compared, and multivariable regression models were developed to evaluate 90-day complications and total direct hospital costs.The cohort included 83,470 patients that underwent RC between 2003 and 2017 and 11% were found to be anemic. On multivariable analysis, preoperative anemia more than doubled the odds of having a complication (odds ratio 2.19 (1.89-2.53)) and significantly increased the risk of major complications (odds ratio 1.51 (1.31-1.75)) at 90-days after RC. Anemic patients had significantly higher 90-days total direct costs due to higher laboratory, pharmacologic, radiology and operating room costs.Anemic cystectomy patients face a 50% increase in the risk of major complications within the first 90-days after surgery. This increased risk persisted after adjusting for patient, hospital and surgical factors. Our study suggests hematocrit level prior to RC may be used as a pre-exisitng condition for increased risk of surgical complications.

Purpose We performed a systematic review to assess the clinical features of cyclophosphamide-associated bladder cancer. Materials and Methods MEDLINE, Web of Science, and Cochrane Library were searched from inception to August 2020 according to PRISMA guidelines. Studies that associated bladder cancer with prior cyclophosphamide use on an individual level were included. Results We identified 121 studies spanning over a 50-year period with 285 patients. The most common malignant indication for cyclophosphamide was lymphoma (25%), while the most common non-malignant indication was ANCA-associated vasculitides (26%). Hematuria and dysuria were the most prevalent symptoms prior to a cyclophosphamide-associated bladder cancer diagnosis, and median age at diagnosis was 55 years. Conventional urothelial carcinoma (UC) was the most common bladder-associated diagnosis (74%), although a broad range of cancer types were represented, notably leiomyosarcoma and squamous cell carcinoma. About half of bladder cancers were muscle invasive at diagnosis and median latency time was 10.0 years; 33% of patients had a bladder cancer related death. Conclusions We describe the largest pooled analysis of patients with cyclophosphamide-associated bladder cancer. These bladder cancers have a propensity for younger age at diagnosis, more advanced stage at diagnosis, and variant histology. There was a substantial number of patients with latency time of ≥20 years independent of cumulative cyclophosphamide dose. These findings support consideration of screening and long-term surveillance of cancer survivors with a history of cyclophosphamide therapy for bladder cancer.

Testicular cancer is the most commonly diagnosed solid-organ neoplasm among young men, with variable incidence across racial groups. Testicular cancer incidence has increased since the 1970s, most notably among white men. Such trends in testicular cancer remain poorly understood. We investigated age-adjusted incidence rates of testicular cancer from 1975 to 2015 using Surveillance, Epidemiology and End Results data to further understand the nature of the temporal trends and potential drivers of disease. Across this time period, white men had the highest incidence and the largest increase in rate; however, we also note more recent increases in the incidence of testicular cancer across all racial groups being examined. PATIENT SUMMARY: We analyzed the rate of testicular cancer in the United States between 1975 and 2015. In that time, white patients had the highest rate and increase in rate of testicular cancer, but non-white patients also had increasing rates of disease.

Purpose Does surgical approach (minimally invasive vs. open) and type (radical vs. partial nephrectomy) affects opioid use and workplace absenteeism. Materials and Methods Retrospective multivariable regression analysis of 2,646 opioid-naïve patients between 18 and 64 undergoing radical or partial nephrectomy via either a minimally invasive vs. open approach for kidney cancer in the United States between 2012 and 2017 drawn from the IBM Watson Health Database was performed. Outcomes included: (1) opioid use in opioid-naïve patients as measured by opioid prescriptions in the post-operative setting at early, intermediate and prolonged time periods and (2) workplace absenteeism after surgery. Results Patients undergoing minimally invasive surgery had a lower odds of opioid use in the early and intermediate post-operative periods (early: odds ratio [OR], 0.77; 95% confidence interval [CI], 0.62–0.97; p=0.02, intermediate: OR, 0.60; 95% CI, 0.48–0.75; p, Graphical Abstract

Rapid infusion catheters (RICs) allow expedient conversion of peripheral intravenous (PIV) catheters to peripheral sheaths; however, little is known about potential complications. In this case, a 64-year-old male polytrauma patient had a 20-gauge PIV catheter in the right cephalic vein upsized to an 8.5 French (Fr) RIC without incident during an arrest with pulseless electrical activity (PEA). On RIC post-placement day two, the patient developed edema and ecchymosis extending from the right dorsal mid-hand to the antecubital fossa, just distal to the RIC insertion point. Compartments were soft; the volar surface (including an arterial line location), fingers, and upper arm were normal. The RIC flushed and returned blood appropriately. Ultrasound revealed a noncompressible cephalic vein either related to the catheter or thrombosis, and imaging of the hand showed an ulnar styloid fracture and a minimally displaced triquetral fracture. The RIC was removed immediately. Over the next week, the areas of ecchymosis developed bullae and then sloughed, leaving open wounds extending into the dermis. The patient later expired from unrelated causes. The area and timing of the skin necrosis were highly suspicious for a catheter-associated complication, despite the presence of the arterial line and small distal fractures. The necrosis was potentially due to thrombosis of the superficial venous outflow system, leading to congestion and skin compromise, but we found no similar reports. Alternatively, the catheter may have ruptured the vein and caused a gravity-dependent ecchymosis, but the volar surface was not impacted, and the catheter was functioning properly. The RIC may also have encroached on the arterial space, decreasing flow, but we would have expected distal hand changes. The only published reports we could find on RIC complications involved a lost guide wire, fragmentation of a catheter during placement, and a case of compartment syndrome, raising the question of whether skin necrosis is truly a rare event or simply underreported with the RIC. Although the exact causal relationship remains unknown in our case, RICs should be removed as soon as possible after immediate stabilization.

A single extracellular stimulus can promote diverse behaviors among isogenic cells by differentially regulated signaling networks. We examined Ca(2+) signaling in response to VEGF (vascular endothelial growth factor), a growth factor that can stimulate different behaviors in endothelial cells. We found that altering the amount of VEGF signaling in endothelial cells by stimulating them with different VEGF concentrations triggered distinct and mutually exclusive dynamic Ca(2+) signaling responses that correlated with different cellular behaviors. These behaviors were cell proliferation involving the transcription factor NFAT (nuclear factor of activated T cells) and cell migration involving MLCK (myosin light chain kinase). Further analysis suggested that this signal decoding was robust to the noisy nature of the signal input. Using probabilistic modeling, we captured both the stochastic and deterministic aspects of Ca(2+) signal decoding and accurately predicted cell responses in VEGF gradients, which we used to simulate different amounts of VEGF signaling. Ca(2+) signaling patterns associated with proliferation and migration were detected during angiogenesis in developing zebrafish.