Genital Dysplasia and Immunosuppression: Why Organ-Specific Therapy Is Important

Background Young patients with Crohn's disease (CD) show a high prevalence of human papillomavirus (HPV) which is the main cause of high-grade squamous intraepithelial lesions (HSIL). A major complication for patients undergoing immunocompromising therapy is the development of genital dysplasia. Methods We report the case of a 32-year-old patient with recurrent genital dysplasia under long-term therapy for CD with a focus on different drug-related, immunosuppressive mechanisms. Results Gynecological examination and biopsy revealed high-grade vulvar intraepithelial neoplasia (VIN) positive for HPV 16 treated with laser vaporization. Due to the combination of HPV positivity, intraoperative multilocularity, and CD, follow-up examinations were performed every 6 months. One year later, the patient showed a VIN at a new location and additionally, a cervical intraepithelial neoplasia (CIN), which were surgically treated. Catch-up HPV vaccination was applied accessorily. After the switch from a TNF-α blocker to vedolizumab, which acts as a gut-selective anti-integrin, the subsequent PAP smear, vulvoscopy, and colposcopy showed no more evidence of dysplasia. Conclusions This case report highlights that gut-selective immunosuppression with vedolizumab might be favorable in young HPV-positive patients due to a good side effect profile. Regular screening and HPV vaccination are a mainstay of dysplasia prevention and control. The risk for HPV-associated dysplasia in immunosuppressed patients is highly dependent on the choice of immunosuppressive therapy

Association of N-terminal pro-B-type natriuretic peptide with mortality in elderly (≥80 years) patients undergoing percutaneous coronary intervention

OBJECTIVES The aim of this study was to determine the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the prognostication of patients ≥80 years of age undergoing percutaneous coronary intervention (PCI). BACKGROUND Elderly patients with coronary artery disease in need of PCI represent a growing patient population. Advanced risk prediction in this frail and comorbid patient population is important. METHODS A total of 460 consecutive patients ≥80 years of age undergoing PCI for acute (ACS) or chronic coronary syndromes (CCS) at the University Hospital Zurich, Switzerland, between January 2016 and December 2018 and with available baseline NT-proBNP levels were included in the analysis. Patients were stratified according to baseline NT-proBNP levels. The primary endpoint was all-cause mortality at a median follow-up of 33 (interquartile range: 3-392) days. RESULTS Median baseline NT-proBNP levels were 1411 (457-3984) ng/L. All-cause mortality was 7.8% in the lowest and 27.8% in the highest NT-proBNP quartile group (p < 0.001). In patients with ACS, all-cause mortality was 4.8% and 30.4% in the lowest and the highest NT-proBNP quartile (p < 0.001), and corresponding rates in patients with CCS were 11.1% and 22.2% (p = 0.38). In multivariable Cox regression analysis, baseline NT-proBNP levels were independently associated with an increased risk of all-cause mortality (adjusted hazard ratio: 1.00, 95% confidence interval: 1.00-1.00, p = 0.04). CONCLUSIONS Baseline NT-proBNP levels were identified as independent predictor of mortality in elderly (≥80 years) patients undergoing PCI. Hence, baseline NT-proBNP allows for the identification of a high-risk elderly patient subset

Understanding the Impact of Sociocultural Gender on Post-acute Sequelae of COVID-19: a Bayesian Approach

Background Women are overrepresented amongst individuals suffering from post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Methods and Findings By using Bayesian models comprising >200 co-variates, we assessed the impact of social context in addition to biological data on PASC in a multi-centre prospective cohort study of 2927 (46% women) individuals in Switzerland. Women more often reported at least one persistent symptom than men (43.5% vs 32.0% of men, p<0.001) six (IQR 5–9) months after SARS-CoV-2 infection. Adjusted models showed that women with personality traits stereotypically attributed to women were most often affected by PASC (OR 2.50[1.25-4.98], p<0.001), in particular when they were living alone (OR 1.84[1.25-2.74]), had an increased stress level (OR 1.06[1.03-1.09]), had undergone higher education (OR 1.30[1.08-1.54]), preferred pre-pandemic physical greeting over verbal greeting (OR 1.71[1.44-2.03]), and had experienced an increased number of symptoms during index infection (OR 1.27[1.22-1.33]). Conclusion Besides gender- and sex-sensitive biological parameters, sociocultural variables play an important role in producing sex differences in PASC. Our results indicate that predictor variables of PASC can be easily identified without extensive diagnostic testing and are targets of interventions aiming at stress coping and social support. Competing Interest Statement CG has received research grants from the Novartis Foundation and speakers fees from Sanofi Genzyme, Switzerland outside of the submitted work. The University Hospital Zurich (CG, RRB, APP, MM, PAK) holds a research contract with GE Healthcare outside of the submitted work. CG and AM have received research grants from Bayer Pharmaceuticals outside of the submitted work. JCS and TS reports (full departmental disclosure) grants from Orion Pharma, Abbott Nutrition International, B. Braun Medical AG, CSEM AG, Edwards Lifesciences Services GmbH, Kenta Biotech Ltd, Maquet Critical Care AB, Omnicare Clinical Research AG, Nestle, Pierre Fabre Pharma AG, Pfizer, Bard Medica S.A., Abbott AG, Anandic Medical Systems, Pan Gas AG Healthcare, Bracco, Hamilton Medical AG, Fresenius Kabi, Getinge Group Maquet AG, Draeger AG, Teleflex Medical GmbH, Glaxo Smith Kline, Merck Sharp and Dohme AG, Eli Lilly and Company, Baxter, Astellas, Astra Zeneca, CSL Behring, Novartis, Covidien, Nycomed, and Phagenesis, outside of the submitted work. The money went into departmental funds, no personal financial gain applies. All other authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work