Immune Checkpoint Inhibitor-Induced Pancreatic Injury: Clinical and Radiological Profile and Response to Steroids.

Background and Aims: Immune checkpoint inhibitor therapy causes numerous immune-related adverse events, including autoimmune pancreatic injury (AIPI), which results in rapid organ atrophy. We profiled the clinico-radiological features, short-term natural history, and response to steroids of AIPI. Methods: We retrospectively reviewed medical records of 229/11,165 (2.1%) adult patients with AIPI. One hundred and ten out of 229 (48%) had abdominal computerized tomography (CT) scan at lipase elevation; data of 110 without pancreatic metastases were analyzed. We analyzed serial CT-based pancreas volumetry data in 48 patients with AIPI (32 with normal CT and 16 with pancreatitis on CT at lipase elevation). We examined impact of steroids on pain and disease course. Results: In AIPI (n = 229), median lipase elevation was 4x upper limit of normal (range: 3-40x). The injury was more often asymptomatic than painful (143/229 (62%) vs 86/229 (38%), P < .000). Majority (83/110 (75%) had normal CT, often in painless vs painful disease: 51/57 (90%) vs 32/53 (60%), P < .001) 25% had interstitial pancreatitis. On serial pancreas volumetry, marked volume (cc) loss occurred 1 year after vs 3 months before lipase elevation in both normal CT (median 81.6 vs 61.3, P = .00) and pancreatitis on CT groups (91.8 vs 60.5, P = .00), ≥20% volume loss occurred in 47% vs 73%, respectively (P = .08). Steroids, when used did not mitigate pain, biochemical relapse, pancreas volume loss or 1-year diabetes incidence (7.2%). Conclusion: Autoimmune pancreatic injury (AIPI) is uniquely characterized by painless lipase elevation, normal pancreas on CT and rapid pancreatic volume loss on follow-up. Steroids do not appear to have a role in management.

Human Papillomavirus Vaccination Uptake in the Rio Grande Valley: Results from a Pilot Community-Based Educational and School-Based Vaccination Program and Its Expansion.

Human papillomavirus (HPV) vaccine is a safe and effective strategy for reducing HPV morbidity and mortality. Schools have become an increasingly attractive setting for delivering vaccinations and supporting vaccination health literacy and decisional support. This study assesses the effectiveness of a community-based, physician-led HPV education campaign (starting in 2016) and onsite middle school-based HPV vaccination program across six school districts (2017, 2019, 2020) in a rural, medically underserved Texas area (Rio Grande Valley). Pre- and post-intervention HPV vaccination rates were tracked against the 2016 National Immunization Survey-Teen target rates (initiation: 49.3%; completion: 32.9%). Summary statistics were stratified by gender, school district, and grade level. The study reached 19,951 students who received HPV vaccines directly or indirectly through our program (10,289 females; 9662 males) (August 2016-August 2022). Of those, 2145 students (1074 females; 1071 males) were vaccinated directly through our program. The overall HPV up-to-date (UTD) rates were 58.8%. The overall median age at HPV vaccine initiation and HPV-UTD (range) was 11 years (9-21) and 12 years (9-20). The overall median interval between HPV vaccine doses (range) was 291 days (146-2968). Recommending HPV vaccine initiation at younger ages increases HPV vaccine completion and providing access to HPV vaccines encourages on-time vaccination and completion.

Treatment of Arrhythmias During Pregnancy.

Cardiac disease is the most common cause of maternal mortality in developed nations. Cardiac arrhythmias are frequent among patients with structural heart disease and may require immediate treatment to prevent hemodynamic instability leading to acute maternal and fetal decompensation. Antiarrhythmic therapy during pregnancy should follow the same principles recommended for nonpregnant individuals. Although multidisciplinary management is recommended, obstetricians, and maternal-fetal medicine specialists may sometimes need to emergently recognize and treat rhythm anomalies before support services become available.

Characteristics, treatment, and outcome of diverticulitis after immune checkpoint inhibitor treatment in patients with malignancies.

PURPOSE: Immune checkpoint inhibitors (ICIs) are efficacious for treating various malignancies. In addition to immune-related adverse events (irAEs), growing evidence suggests that ICIs might also be associated with diverticulitis. We aim to assess the clinical presentations and management of colonic diverticulitis among cancer patients after ICI treatment. METHODS: A retrospective study was conducted on ICI-treated adult cancer patients between 01/2010 and 06/2020. Patients were grouped based on when diverticulitis developed relative to ICI treatment, either before (controls) or after (cases). Patient clinical characters, treatment, and outcomes were compared between both groups. RESULTS: 77 eligible patients were included: 63 patients developed diverticulitis after ICI exposure (46 had initial episode after ICI exposure, 17 had a history of diverticulitis prior then recurred after ICI exposure), and 14 had diverticulitis before ICI exposure. Diverticulitis occurred after a median of 129 days after ICI initiation. Clinical characteristics overlapped with traditional diverticulitis. 93% of patients had symptom resolution after treatment, while 23.8% experienced complications. These patients exhibited higher rates of hospitalization (87% vs 48%, P = 0.015) and surgery/interventional radiology procedures (27% vs 0, P = 0.002), and worse overall survival (P = 0.022). History of diverticulitis was not associated with a more severe disease course. Immunosuppressants (e.g., corticosteroids) were rarely required unless for concurrent ICI-mediated colitis. CONCLUSION: Colonic diverticulitis can occur after ICI therapy at very low incidence (0.5%). Its clinical presentation, evaluation, and management are similar to traditional diverticulitis, but associated with higher complication rates requiring surgical intervention and has lower overall survival.

The genomic landscape of low-grade serous ovarian/peritoneal carcinoma and its impact on clinical outcomes.

OBJECTIVE: Low-grade serous carcinoma (LGSOC) is a rare epithelial ovarian/peritoneal cancer characterized by younger age at diagnosis, relative chemoresistance, prolonged overall survival (OS), and mutations in the mitogen activated protein kinase (MAPK) pathway compared to high-grade serous carcinoma. We describe the genomic profile of LGSOC by next generation sequencing (NGS) and evaluated its potential relationship to clinical outcomes. METHODS: The study included 215 women with LGSOC with: 1) pathologically confirmed LGSOC, 2) availability of NGS data, and 3) adequate clinical data. Clinical subgroups were compared for progression-free survival (PFS) and OS. Multivariable Cox regression analysis was performed. RESULTS: Median age at diagnosis was 46.6 years. The majority had a stage III ovarian primary. One or more mutations were identified in 140 (65.1%) cases; 75 (34.9%) had none. The most common mutations were KRAS (n = 71; 33.0%), NRAS (n = 24; 11.2%), and BRAF (n = 18; 8.4%). Patients with MAPK-mutated tumors (n = 113) (52.6%) had a significantly longer OS compared to those with tumors lacking MAPK pathway mutations (n = 102) (47.4%) [median OS, 147.8 months (95% CI,119.0-176.6) versus 89.5 months (95% CI, 61.4-117.7) (p = 0.01)], respectively. Median OS for patients with MAPK-mutated tumors was also significantly better than for patients whose tumors had no mutations (n = 75) [median OS, 147.8 months (95% CI, 119.0-176.6) versus 78.0 months (95% CI, 57.6-98.3)], respectively (p = 0.001). Median OS for patients with non-MAPK-mutated tumors (n = 27) was 125.1 months (95% CI, 83.9-166.3). In multivariable analysis, having a MAPK mutation was associated with improved OS. CONCLUSIONS: Patients with MAPK-mutated tumors have a significantly improved OS compared to those without MAPK-mutated tumors.

Automation of semen analysis using flow cytometer in comparison with manual methods.

In order to standardize techniques and limit the effect of human factors on the results of analyses of biological fluids, automation seems to be mandatory. In an attempt to automate semen analysis, computer assisted sperm analysis (CASA) system has been developed, however its use is still limited and its practical applications have many criticisms. In a trial to automate semen analysis, this study aimed to evaluate the usefulness of flow cytometer in the detection of some seminal parameters in comparison with the traditional manual methods. Isolated spermatogenic cells and isolated sperms from semen and EDTA blood of volunteers were analyzed by flow cytometer in order to define their respective regions. Ejaculates of 28 male patients were subjected to routine semen analyses, leucocytes detection by peroxidase test and monoclonal antibody CD53 using flow cytometer after preparation of the patients' semen samples for flow cytometeric analysis. A highly significant correlation (r=0.96, p= 0.001) of absolute neutrophils (pus cells) detected by peroxidase versus flow cytometer using CD53 monoclonal antibody. A poor correlation (r=0.39, p=0.035) of sperm counts assessed by manual technique and flow cytometer and a spurious sperm counts of 1.08 million/ml detected by flow cytometery in azoospermic patients. Flow cytometer could be used for the assessment of pus cells in semen but seems to be non reliable for the assessment of sperm count if gating depend on sperm size and granularity alone.