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Importance: Recurrent urinary tract infections (rUTIs) affect 2-10% of adult women and are associated with a significant effect on quality of life, daily activities, and mental health., Objective: The aim of this study was to identify clinical characteristics associated with rUTIs among women seeking care for pelvic floor disorders at an academic tertiary urogynecology clinic., Study Design: A retrospective case-control study of women presenting to an academic tertiary urogynecology clinic was conducted. Cases were women with rUTIs, defined as ≥2 UTIs in 6 months or ≥3 within 1 year. Controls were women with no culture documented UTIs. Cases were matched 2:1 to controls by age and body mass index. Demographic and clinical characteristics were compared between cases and controls, and bivariate characteristics with P values ≤0.2 were assessed for an independent association with rUTIs by multivariable logistic regression., Results: A total of 285 cases with rUTIs were identified, and 150 matched controls had a mean (SD) age of 72 (11.8) years and a body mass index of 29.6 (6.7; calculated as weight in kilograms divided by height in meters squared). Multivariable analysis revealed that prolapse beyond the introitus (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.13-0.60), parity (OR, 1.33; 95% CI, 1.08-1.64), Charlson Comorbidity Index (OR, 1.66; 95% CI, 1.37-2.03), and postvoid residual volume ≥100 mL (OR, 4.05; 95% CI, 2.01, 8.18) were associated with rUTIs., Conclusions: In this ambulatory urogynecologic population, prolapse through the introitus was negatively associated with rUTIs, whereas parity, increased medical comorbidities, and elevated postvoid residual volume were positively associated with rUTI. Future research should seek an increased understanding of these factors associated with rUTI to implement effective preventive strategies., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2024 American Urogynecologic Society. All rights reserved.)

Objective: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma., Summary Background Data: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization., Methods: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics., Results: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients., Conclusions: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy for which factors predictive of disease-specific survival (DSS) are poorly defined., Methods: Patients from six centers (2005-2020) with clinical stage I-II MCC who underwent sentinel lymph node (SLN) biopsy were included. Factors associated with DSS were identified using competing-risks regression analysis. Risk-score modeling was established using competing-risks regression on a training dataset and internally validated by point assignment to variables., Results: Of 604 patients, 474 (78.5%) and 128 (21.2%) patients had clinical stage I and II disease, respectively, and 189 (31.3%) had SLN metastases. The 5-year DSS rate was 81.8% with a median follow-up of 31 months. Prognostic factors associated with worse DSS included increasing age (hazard ratio [HR] 1.03, p = 0.046), male sex (HR 3.21, p = 0.021), immune compromise (HR 2.46, p = 0.013), presence of microsatellites (HR 2.65, p = 0.041), and regional nodal involvement (1 node: HR 2.48, p = 0.039; ≥2 nodes: HR 2.95, p = 0.026). An internally validated, risk-score model incorporating all of these factors was developed with good performance (AUC 0.738). Patients with ≤ 4.00 and > 4.00 points had 5-year DSS rates of 89.4% and 67.2%, respectively. Five-year DSS for pathologic stage I/II patients with > 4.00 points (n = 49) was 79.8% and for pathologic stage III patients with ≤ 4.00 points (n = 62) was 90.3%., Conclusions: A risk-score model, including patient and tumor factors, based on DSS improves prognostic assessment of patients with clinically localized MCC. This may inform surveillance strategies and patient selection for adjuvant therapy trials., (© 2022. Society of Surgical Oncology.)

Background: The public health response to the global COVID-19 pandemic has varied widely by region. In Africa, uptake of effective COVID-19 vaccines has been limited by accessibility and vaccine hesitancy. The aim of this study was to compare perceptions of COVID-19 infection and vaccination between pregnant women and non-pregnant adults in four regions of Cameroon, located in Central Africa., Methods: A cross-sectional survey study was conducted at urban and suburban hospital facilities in Cameroon. Participants were randomly selected from a convenience sample of adult pregnant and non-pregnant adults in outpatient clinical settings between June 1st and July 14th, 2021. A confidential survey was administered in person by trained research nurses after obtaining written informed consent. Participants were asked about self-reported sociodemographics, medical comorbidities, perceptions of COVID-19 infection, and vaccination. Descriptive statistics were used for survey responses and univariate and multivariable logistic regression models were created to explore factors associated with COVID-19 vaccine acceptability., Results: Fewer than one-third of participants were interested in receiving the COVID-19 vaccine (31%, 257/835) and rates did not differ by pregnancy status. Overall, 43% of participants doubted vaccine efficacy, and 85% stated that the vaccine available in Africa was less effective than vaccine available in Europe. Factors independently associated with vaccine acceptability included having children (aOR = 1.5; p = 0.04) and higher education (aOR = 1.6 for secondary school vs primary/none; p = 0.03). Perceived risks of vaccination ranged from death (33%) to fetal harm (31%) to genetic changes (1%). Health care professionals were cited as the most trusted source for health information (82%, n = 681)., Conclusion: COVID-19 vaccine hesitancy and misinformation in Cameroon was highly prevalent among pregnant and non-pregnant adults in 2021 while vaccine was available but not recommended for use in pregnancy. Based on study findings, consistent public health messaging from medical professionals about vaccine safety and efficacy and local production of vaccine are likely to improve acceptability., Competing Interests: The authors have declared that no competing interests exist.

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients., Competing Interests: Competing interests: ZE: Advisory boards: Array, Pfizer, OncoSec, Regeneron, Genentech, Novartis, Natera. Research funding: Novartis, Pfizer, Boehringer-Ingelheim. JFT: Advisory boards: BMS Australia, MSD Australia, GSK, Provectus Inc. Travel support: GSK, Provectus Inc and Novartis. TJH: Research funding: Genentech, SkylineDX. EKB: Research funding: SkylineDx, Honorarium: Excite International inc. DEG: Honoraria: BMS, Novartis, Q biotics. GK; Advisory Board: Merck. AVA: Advisory Boards: Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Provectus, Sanofi, Sirius Medical, 4SC Research funding: Amgen, Merck-Pfizer. JV: Speaker: Caste Biosciences. GB: Research funding: Istari Oncology, Delcath, Oncosec Medical, Replimune, Checkmate Pharmaceuticals. ROB: Advisory boards: Amgen, BD/BARD, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche and Sanofi Genzyme. Research funding: Bristol-Myers Squibb, SkyLineDx. Speaker honorarium: Roche and Pfizer. Shareholder in SATMEG Ventures AB. NIK: Advisory boards: Bristol-Myers Squibb, AstraZeneca, Regeneron, Array, Immunocore, Merck, Incyte, Jounce Therapeutics,Pfizer,Novartis, Nektar,Castle Biosciences, Instil Bio. Research funding: Bristol-Myers Squibb, Merck, Novartis, Celgene, Replimune, Amgen, Regneron, HUYA, GlaxoSmithKline Stocks: Bellicum Pharmaceuticals, Amarin Corporation, Asensus Surgical., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma., Methods: An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed., Results: Of 112 patients, median age at T-VEC initiation was 69 years (range 21-93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE)., Conclusions: T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response., (© 2021. Society of Surgical Oncology.)

Background: In sentinel lymph node (SLN)-positive melanoma, two randomized trials demonstrated equivalent melanoma-specific survival with nodal surveillance vs completion lymph node dissection (CLND). Patients with microsatellites, extranodal extension (ENE) in the SLN, or >3 positive SLNs constitute a high-risk group largely excluded from the randomized trials, for whom appropriate management remains unknown., Study Design: SLN-positive patients with any of the three high-risk features were identified from an international cohort. CLND patients were matched 1:1 with surveillance patients using propensity scores. Risk of any-site recurrence, SLN-basin-only recurrence, and melanoma-specific mortality were compared., Results: Among 1,154 SLN-positive patients, 166 had ENE, microsatellites, and/or >3 positive SLN. At 18.5 months median follow-up, 49% had recurrence (vs 26% in patients without high-risk features, p < 0.01). Among high-risk patients, 52 (31%) underwent CLND and 114 (69%) received surveillance. Fifty-one CLND patients were matched to 51 surveillance patients. The matched cohort was balanced on tumor, nodal, and adjuvant treatment factors. There were no significant differences in any-site recurrence (CLND 49%, surveillance 45%, p = 0.99), SLN-basin-only recurrence (CLND 6%, surveillance 14%, p = 0.20), or melanoma-specific mortality (CLND 14%, surveillance 12%, p = 0.86)., Conclusions: SLN-positive patients with microsatellites, ENE, or >3 positive SLN constitute a high-risk group with a 2-fold greater recurrence risk. For those managed with nodal surveillance, SLN-basin recurrences were more frequent, but all-site recurrence and melanoma-specific mortality were comparable to patients treated with CLND. Most recurrences were outside the SLN-basin, supporting use of nodal surveillance for SLN-positive patients with microsatellites, ENE, and/or >3 positive SLN., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the influence of injury site and severity as predictors of mental health outcomes in the initial 12 months following traumatic injury. Using a multisite, longitudinal study, participants with a traumatic physical injury (N = 1,098) were assessed during hospital admission and followed up at 3 months (N = 932, 86%) and at 12 months (N = 715, 71%). Injury site was measured using the Abbreviated Injury Scale 90, and objective injury severity was measured using the Injury Severity Score. Participants also completed the Hospital Anxiety and Depression Scale and the Clinician Administered Post-traumatic Stress Disorder (PTSD) Scale. A random intercept mixed modelling analysis was conducted to evaluate the effects of site and severity of injury in relation to anxiety, PTSD, and depressive symptoms. Injury severity, as well as head and facial injuries, was predictive of elevated PTSD symptoms, and external injuries were associated with both PTSD and depression severity. In contrast, lower extremity injuries were associated with depressive and anxiety symptoms. The findings suggest that visible injuries are predictive of reduced mental health, particularly PTSD following traumatic injury. This has clinical implications for further advancing the screening for vulnerable injured trauma survivors at risk of chronic psychopathology., (Copyright © 2018 John Wiley & Sons, Ltd.)

The 22q11.2 deletion syndrome is one of the most common deletion syndromes in newborns. Some affected newborns may be diagnosed shortly after birth because of the presence of heart defects, palatal defects, or severe immune deficiencies. However, diagnosis is often delayed in patients presenting with other associated conditions that would benefit from early recognition and treatment, such as speech delays, learning difficulties, and schizophrenia. Fluorescence in situ hybridization (FISH) is the gold standard for deletion detection, but it is costly and time consuming and requires a whole blood specimen. Our goal was to develop a suitable assay for population-based screening of easily collectible specimens, such as buccal swabs and dried blood spots (DBS). We designed a pyrosequencing assay and validated it using DNA from FISH-confirmed 22q11 deletion syndrome patients and normal controls. We tested DBS from nine patients and paired buccal cell and venous blood specimens from 20 patients. Results were 100% concordant with FISH assay results. DNA samples from normal controls (n = 180 cell lines, n = 15 DBS, and n = 88 buccal specimens) were negative for the deletion. Limiting dilution experiments demonstrated that accurate results could be obtained from as little as 1 ng of DNA. This method represents a reliable and low-cost alternative for detection of the common 22q11.2 microdeletions and can be adapted to high-throughput population screening., (Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)