Use of Sotrovimab in Pregnancy: Experiences from the COVID-19 International Drug Pregnancy Registry.

INTRODUCTION: Available data regarding the safety and efficacy of sotrovimab in pregnant patients remain limited due to their exclusion from clinical trials. METHODS: The COVID-19 International Drug Pregnancy Registry (COVID-PR) was established to gather comprehensive safety data from pregnant women who have received monoclonal antibody (mAb) or antiviral treatments for mild, moderate, or severe coronavirus disease 2019 (COVID-19) during pregnancy. Participants actively contributed self-reported data concerning their COVID-19 symptoms, in addition to sociodemographic and health-related characteristics. Obstetric, neonatal, and infant outcomes were also documented, with follow-up extending up to 12 months after childbirth. RESULTS: As of 30 November 2023, sotrovimab was administered to 39 participants enrolled in the COVID-PR. At the time of this report, 26 participants had given birth, with nine deliveries performed via cesarean section. The infants' birthweight ranged from 2381 g to 4762 g, with a mean of 3439.91 g. Twenty-five infants were born at ≥37 weeks. A total of 31 adverse events (AEs) were reported by 12 participants. The most frequently reported AE was gestational hypertension, observed in three participants. COVID-19 re-infection, fatigue, gestational diabetes, headache, and morning sickness were each reported by two participants. Of the reported AEs, eight (in five participants) were classified as serious, including four AEs (prolonged labor, pre-eclampsia, polyhydramnios, premature labor) that affected pregnancy. Seven of these eight serious AEs (SAEs) were found to be unrelated to sotrovimab, with one event (urinary retention) not assessable. A total of 44 AEs were reported in 19 delivered infants or in utero fetuses. The most common were COVID-19 (n = 6 events), ear infection (n = 5 events), neonatal dyspnea (n = 3 events), and respiratory syncytial virus infection (n = 3 events). Sixteen AEs (in 11 infants/fetuses) were classified as serious, including one report each of fetal cardiac disorder, congenital ankyloglossia, persistent right umbilical vein, and congenital hydronephrosis; the latter was considered a major congenital malformation. For all assessable SAEs, causality of sotrovimab treatment was ruled out based on lack of a temporal relationship alone or in combination with absence of a plausible mechanism. CONCLUSION: A sizable proportion of sotrovimab-treated participants in the COVID-PR had underlying medical conditions associated with an increased risk of severe COVID-19. None of the assessable SAEs were considered to be related to sotrovimab treatment.

Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis is a rare, chronic cholestatic liver disease characterized by the destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. Whether elafibranor, an oral, dual peroxisome proliferator-activated receptor (PPAR) α and δ agonist, may have benefit as a treatment for primary biliary cholangitis is unknown. METHODS: In this multinational, phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients with primary biliary cholangitis who had had an inadequate response to or unacceptable side effects with ursodeoxycholic acid to receive once-daily elafibranor, at a dose of 80 mg, or placebo. The primary end point was a biochemical response (defined as an alkaline phosphatase level of <1.67 times the upper limit of the normal range, with a reduction of ≥15% from baseline, and normal total bilirubin levels) at week 52. Key secondary end points were normalization of the alkaline phosphatase level at week 52 and a change in pruritus intensity from baseline through week 52 and through week 24, as measured on the Worst Itch Numeric Rating Scale (WI-NRS; scores range from 0 [no itch] to 10 [worst itch imaginable]). RESULTS: A total of 161 patients underwent randomization. A biochemical response (the primary end point) was observed in 51% of the patients (55 of 108) who received elafibranor and in 4% (2 of 53) who received placebo, for a difference of 47 percentage points (95% confidence interval [CI], 32 to 57; P<0.001). The alkaline phosphatase level normalized in 15% of the patients in the elafibranor group and in none of the patients in the placebo group at week 52 (difference, 15 percentage points; 95% CI, 6 to 23; P = 0.002). Among patients who had moderate-to-severe pruritus (44 patients in the elafibranor group and 22 in the placebo group), the least-squares mean change from baseline through week 52 on the WI-NRS did not differ significantly between the groups (-1.93 vs. -1.15; difference, -0.78; 95% CI, -1.99 to 0.42; P = 0.20). Adverse events that occurred more frequently with elafibranor than with placebo included abdominal pain, diarrhea, nausea, and vomiting. CONCLUSIONS: Treatment with elafibranor resulted in significantly greater improvements in relevant biochemical indicators of cholestasis than placebo. (Funded by GENFIT and Ipsen; ELATIVE ClinicalTrials.gov number, NCT04526665.).

The assessment of knowledge and attitudes of men in Serbia about prostate cancer and possibilities for its early detection and treatment in 2011: a cross-sectional study.

PURPOSE: To assess the knowledge and attitudes of men in Serbia about prostate cancer (PCa) and possibilities for its early detection and treatment in 2011. METHODS: This cross-sectional study included 407 men of various ages and education levels selected randomly and divided in 2 groups according to age (up to 40 and over 40 years). The assessment of knowledge and attitudes was based on a survey made up of 12 multiple choice questions conducted with direct contact with respondents from October 15th to December 15th 2011 with their voluntary consent. The results were evaluated in the total sample and between the groups. RESULTS: Patient groups significantly differed according to knowledge about PCa treatment success (p<0.001) and stage in which PCa is most frequently detected (p<0.001) as well as according to attitudes about community-based interventions for increasing the awareness of PCa (p<0.001). Sixty-one percent of respondents over 50 years hadn't done preventive prostate examination despite recommendations. Ninety percent of all respondents believed the community-based intervention should have been implemented in Serbia to increase the men's awareness of PCa. CONCLUSION: The study reported lack of men's knowledge about PCa in Serbia in 2011, while there was a common agreement among men on the necessity of spreading more information about this disease.

Primary dorsal buccal mucosa graft urethroplasty for anterior urethral strictures in patients with lichen sclerosus.

PURPOSE: To report our ongoing experience with dorsal buccal mucosa graft (BMG) urethroplasty for the primary repair of anterior urethral strictures in patients with lichen sclerosus (LS). PATIENTS AND METHODS: A total of 32 men with LS underwent BMG urethroplasty from January 2010 to September 2012. In 27 patients, stricture was limited to the penile urethra, while in five patients, both bulbar and penile urethra were involved. In these five patients, the entire anterior urethra was replaced with BMG. In nine (28.1%) younger patients (mean age 38.2 years, range 33-45), with adverse local conditions and significant scarring, two-stage repair was done. The paired t test was performed on preoperative and postoperative Qmax as well as on preoperative and postoperative post-void residual urine volume, and the Fisher exact test was used to assess success between treatment groups. The chi-squared test was used to compare categorical data. RESULTS: The overall success rate was 90.6%. Complications occurred in 9.4% of the patients (3 of 32) including hematoma in two patients and fistula in one patient. In this cohort of patients, mean preoperative Qmax was 6.2 ml per second (range 2.6-10.2) versus 18.2 (range 15.8-21.2) postoperatively (at 9 months), which was statistically significant (p < 0.002). Also, mean preoperative post-void residual urine volume was 110 ml (range 75-180) versus 19 ml (range 10-40) postoperatively at 9 months, which was statistically significant (p < 0.004). CONCLUSION: Buccal mucosa is the most reliable graft for repairing anterior urethral strictures in patients with LS. Minimal complications are observed, even in cases of long stenosis completely afflicting anterior urethra.

Diode laser vaporization of prostate as treatment for benign prostatic enlargement: initial results of 73 patients with 1 year follow-up.

OBJECTIVE: Our objective is to evaluate the efficacy, safety and 12 month outcome of a 980 nm diode laser with Twister fiber in the treatment of benign prostatic enlargement. MATERIALS AND METHODS: Between February 2011 and January 2013, 73 patients with benign pros- tatic enlargement had undergone diode laser vaporization of prostate at our institution. The fol- lowing parameters were assessed at baseline, and after a follow-up period of 3 and 12 months: International Prostate Symptom Score, peak urinary flow rate, post-void residual urine volume, and quality of life score. RESULTS: The procedure was completed successfully in all patients with no intraoperative complications. At 12 months postoperatively the percentage improvements in IPSS was -69.09%, Qmax +197%, PVR -88.54%, and QoL -68.29%. CONCLUSION: Diode laser vaporization of prostate is safe and effective method for treatment of benign prostatic enlargement.

Genitourinary injuries associated with pelvic fractures.

INTRODUCTION: Pelvic fractures represent approximately 3% of all skeletal injuries. About 15% of patients with pelvic fractures have associated bladder or urethral injuries. The most common causes of pelvic fracture are motor vehicle accidents, motorcycle crashes, motor vehicles striking pedestrians, and falls. MATERIAL AND METHODS: Retrospective study included the patients treated in the Emergency Center, Clinical Center of Serbia, Belgrade, between 2000 and 2009. Of 7445 patients, there were 894 injuries of the urinary tract and 376 pelvic fractures; 55 patients with pelvic fractures (14.6%) had bladder or urethral injuries. There were 31 patients with bladder injuries, 22 patients with urethral injuries, and two patients with associated injuries of the posterior urethra and the bladder neck. RESULTS: The bladder injuries were treated by surgical exploration, cystostomy, suture of the bladder lesions and urethral catheterization. Urethral injuries were treated by primary cystostomy and urethral reconstruction and catheterization in 18 patients (82%), while cystofix-cystostomy was performed in four patients (18%). DISCUSSION: Genitourinary injuries increase overall mortality in patients with pelvic fracture, compared with traumas without associated GU injuries. These patients require multidisciplinary approach, preferably in tertiary institutions.