Cumulative Lifetime Violence and Bacterial Vaginosis Infection in Sexually Transmitted Infections: Findings From a Retrospective Cohort Study Among Black Women at Risk for HIV.

Introduction: Bacterial vaginosis is the most common vaginal condition among women of reproductive age and has been associated with sexually transmitted infections. This study examines the association between cumulative lifetime violence exposure, bacterial vaginosis, and sexually transmitted infections among Black women at risk for HIV. Methods: HIV-negative Black women in a retrospective cohort study (N=230) completed survey questions on cumulative violence (exposure to sexual or physical abuse before age 18 years and exposure to intimate partner violence or sexual violence [partner or other] after age 18 years and past year), bacterial vaginosis (lifetime and past year), and sexually transmitted infection diagnosis (lifetime and past year). Logistic regression models estimated the associations between cumulative violence, bacterial vaginosis, and sexually transmitted infections. Bacterial vaginosis was examined as a moderator in the association between cumulative violence and sexually transmitted infections. Results: Many women reported cumulative violence exposure (40%), lifetime bacterial vaginosis diagnosis (53%), and lifetime sexually transmitted infection diagnosis (73%). Cumulative violence experience was significantly associated with increased adjusted odds of lifetime bacterial vaginosis diagnosis (AOR=1.98; 95% CI=1.10, 3.54). Lifetime bacterial vaginosis diagnosis (AOR=2.76; 95% CI=1.45, 5.22) and past-year bacterial vaginosis diagnosis (AOR=2.16; 95% CI=1.14, 4.10) were significantly associated with increased odds of lifetime sexually transmitted infection diagnosis. Lifetime bacterial vaginosis diagnosis (AOR=2.10; 95% CI=1.19, 3.70) and past-year bacterial vaginosis diagnosis (AOR=3.00; 95% CI=1.70, 5.31) were significantly associated with past-year sexually transmitted infection diagnosis. Lifetime bacterial vaginosis infection significantly increased the odds of lifetime sexually transmitted infection diagnosis with increasing cumulative violence exposure. Conclusions: Our findings support educating and screening Black women who experience cumulative violence for bacterial vaginosis to reduce the risk of untreated bacterial vaginosis and sexually transmitted infections.

Challenges and Opportunities for Clinician Implicit Bias Training: Insights from Perinatal Care Stakeholders.

Introduction: In an attempt to address health inequities, many U.S. states have considered or enacted legislation requiring antibias or implicit bias training (IBT) for health care providers. California's "Dignity in Pregnancy and Childbirth Act" requires that hospitals and alternative birthing centers provide IBT to perinatal clinicians with the goal of improving clinical outcomes for Black women and birthing people. However, there is as yet insufficient evidence to identify what IBT approaches, if any, achieve this goal. Engaging the experiences and insights of IBT stakeholders is a foundational step in informing nascent IBT policy, curricula, and implementation. Methods: We conducted a multimethod community-based participatory research study with key stakeholders of California's IBT policy to identify key challenges and recommendations for effective clinician IBT. We used focus groups, in-depth interviews, combined inductive/deductive thematic analysis, and multiple techniques to promote rigor and validity. Participants were San Francisco Bay Area-based individuals who identified as Black or African American women with a recent hospital birth (n=20), and hospital-based perinatal clinicians (n=20). Results: We identified numerous actionable challenges and recommendations regarding aspects of (1) state law; (2) IBT content and format; (3) health care facility IBT implementation; (4) health care facility environment; and (5) provider commitment and behaviors. Patient and clinician insights overlapped substantially. Many respondents felt IBT would improve outcomes only in combination with other antiracism interventions. Health Equity Implications: These stakeholder insights offer policy-makers, health system leaders, and curriculum developers crucial guidance for the future development and implementation of clinician antibias interventions.

Global Trends of Prostate Cancer by Age, and Their Associations With Gross Domestic Product (GDP), Human Development Index (HDI), Smoking, and Alcohol Drinking.

BACKGROUND: We aimed to examine the global disease burden and trends of prostate cancer incidence and mortality by age, and their associations with gross domestic product (GDP), human development index (HDI), smoking, and alcohol drinking. MATERIALS AND METHODS: We retrieved the Global Cancer Observatory (GLOBOCAN) database for the incidence and mortality of prostate cancer in 2020; the World Bank for GDP per capita; the United Nations for HDI; the WHO Global Health Observatory for prevalence of smoking and alcohol drinking; the Cancer Incidence in 5 Continents (CI5), WHO mortality database, for trend analysis. We presented the prostate cancer incidence and mortality using age-standardized rates. We examined their associations with GDP, HDI, smoking, and alcohol drinking by Spearman's correlations and multivariable regression. We estimated the 10-year trend of incidence and mortality by joinpoint regression analysis with average annual percent change with 95% confidence intervals in different age groups. RESULTS: A wide variation in the burden of prostate cancer with the highest mortality found in low-income countries while the highest incidence was observed in high-income countries. We found moderate to high positive correlations for GDP, HDI, and alcohol drinking with prostate cancer incidence, whilst a low negative correlation was observed for smoking. Globally, there was an increasing incidence but decreasing mortality of prostate cancer, and such trends were particularly prominent in Europe. Notably, the incidence increase was also found in the younger population aged <50 years. CONCLUSIONS: There was a global variation in the burden of prostate cancer associated with GDP, HDI, smoking, and alcohol drinking.

Characterising a syndemic among black women at risk for HIV: the role of sociostructural inequity and adverse childhood experiences.

Objectives Black women disproportionately experience STIs (including HIV/AIDS), gender-based violence, substance misuse and mental health conditions. Addressing a gap in syndemic research, we characterised comorbidity overlap within the context of sociostructural inequities and adverse childhood experiences (ACEs) among black women in Baltimore, Maryland. Methods Between 2015 and 2018, black women (n=305) were recruited from STI clinics in Baltimore, Maryland. Among those with complete survey data (n=230), we conducted a latent class analysis to differentiate women based on their profile of the following syndemic comorbidities: STIs, adult sexual victimisation, substance misuse and mental health disorders. We then examined the association between ACEs and syndemic latent class membership. Results Thirty-three percent of women experienced three to nine ACEs before age 18 years, and 44% reported four to six comorbidities. The two-class latent class solution demonstrated the best fit model, and women were categorised in either class 1 (past-year STI; 59%) or class 2 (syndemic comorbidities; 41%). Women in class 2 were more likely to report unstable housing (10% vs 3%) and identify as bisexual/gay (22% vs 10%) than women in class 1. ACEs were significantly associated with an increased likelihood of class 2 membership. Conclusions This study reinforces the importance of screening for ACEs and offering trauma-informed, integrated care for black women with syndemic comorbidities. It also highlights the critical nature of tailoring interventions to improve sociostructural equity, preventing and reducing syndemic development.

Infection Rate after Transperineal Prostate Biopsy with and without Prophylactic Antibiotics: Results from a Systematic Review and Meta-Analysis of Comparative Studies.

PURPOSE: We performed a systematic review comparing the incidence of infectious complications following transperineal ultrasound-guided prostate biopsy (TPB) in cases utilizing antibiotic prophylaxis (AP) vs cases not utilizing antibiotic prophylaxis (NAP). MATERIALS AND METHODS: The incidences of complications were pooled using the Cochran-Mantel-Haenszel method with the random effect model and expressed as risk ratio (RR). RR higher than 1 indicates an increased risk of complication in patients undergoing TPB without antibiotics. Statistical significance was set at p <0.05 and 95% CI. RESULTS: A total of 1,748 papers were retrieved. After the screening process, 8 studies were included in the quantitative analysis (4 retrospective, and 4 prospective and nonrandomized), reporting on 3,662 patients. A total of 2,368 patients underwent TPB utilizing AP and 1,294 underwent TPB utilizing NAP. The pooled rates of post-biopsy fever from 6 available studies reporting this parameter were 0.69% in the AP group and 0.47% in the NAP group (RR: 1.02, 95% CI: 0.02-44.55, p=0.99). The pooled rates of post-biopsy genitourinary infections from 8 available studies reporting this parameter were 0.11% in the AP group and 0.31% in the NAP group (RR: 2.09, 95% CI: 0.54-8.10, p=0.29). The pooled rates of post-biopsy sepsis over 8 studies reporting this parameter were 0.13% in the AP group and 0.09% in the NAP group (RR: 1.09, 95% CI: 0.21-5.61, p=0.92). The pooled rates of post-biopsy readmission for infections over 8 studies reporting this parameter were 0.13% in the AP group and 0.23% in the NAP group (RR: 1.29, 95% CI: 0.31-5.29, p=0.73). Death due to post-biopsy sepsis did not occur in any study. CONCLUSIONS: This systematic review found no significant difference in infection rate, fever, sepsis or readmission rate after TPB between those cases utilizing AP and those cases without AP.

A Global Trend Analysis of Kidney Cancer Incidence and Mortality and Their Associations with Smoking, Alcohol Consumption, and Metabolic Syndrome.

BACKGROUND: Kidney cancer is a major urological disease globally, with more than 400 000 new cases diagnosed every year. OBJECTIVE: To investigate incidence and mortality trends for kidney cancer and their associations with modifiable risk factors for kidney cancer. DESIGN, SETTING, AND PARTICIPANTS: The most up-to-date figures on kidney cancer incidence and mortality were collected from the GLOBOCAN database and the Cancer Incidence in Five Continents (CI5). Data on total alcohol consumption and the prevalence of smoking, overweight, diabetes, and hypertension were extracted from the World Health Organization Global Health Observatory data repository. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Age-standardized rates (ASRs) for incidence and mortality and their correlations with potential risk factors for kidney cancer were investigated. Multivariable linear regression analysis was also conducted. The 10-yr temporal patterns for incidence are presented as the average annual percent change with 95% confidence interval using joinpoint regression analysis. RESULTS AND LIMITATIONS: Globally, there is wide variation in kidney cancer incidence and mortality. There were positive correlations between rates of smoking, alcohol consumption, and overweight and ASRs of kidney cancer incidence and mortality. Multivariable regression analysis revealed that alcohol consumption and overweight were significant risk factors for kidney cancer incidence, while smoking and alcohol consumption were significant risk factors for kidney cancer mortality. There was an increasing trend for the incidence of kidney cancer globally, with a particularly prominent trend for European countries. Of note, increasing incidence of kidney cancer is evident even for younger individuals aged <50 yr. However, cancer registries vary by country and period and there is a lack of data regarding the severity of risk factors and disease characteristics such as the distribution of histological groups, tumor grading, and staging. CONCLUSIONS: There is an increasing trend for kidney cancer incidence globally, particularly in European countries and the younger population. Modifiable risk factors for kidney cancer incidence and mortality have been identified. The increasing incidence of kidney cancer among younger individuals is worrying and warrants early action on possible preventive measures. PATIENT SUMMARY: The incidence of kidney cancer has been increasing globally, particularly in European countries and the younger population. Risk factors include smoking, alcohol consumption, overweight, and hypertension, and these factors are all modifiable.

Intravesical Chemohyperthermia vs. Bacillus Calmette-Guerin Instillation for Intermediate- and High-Risk Non-muscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.

Background: The efficacy of intravesical chemotherapy maintenance for patients with non-muscle invasive bladder cancer (NMIBC) is inferior compared to intravesical bacillus Calmette-Guerin (BCG). How intravesical chemohyperthermia (CHT) compares with BCG is under investigation. Objective: To compare the oncological outcomes and safety profile between intravesical CHT and BCG treatment for intermediate- and high-risk NMIBC. Methods: We performed a systematic review and meta-analysis of clinical studies comparing CHT with BCG for intermediate- and high-risk NMIBC patients. A comprehensive literature search on OVID MEDLINE, EMBASE, and Cochrane Library was conducted. Risk of bias was assessed by the Cochrane RoB tool and ROBINS-I. Certainty of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: A total of 2,375 articles were identified and five studies were finally included. Among them, four randomised trials comprising 327 patients (CHT group: 156 patients; BCG group: 171 patients) were included in the meta-analysis. There were no significant differences in the 24-36 months recurrence rates (CHT: 29.5%, BCG: 37.4%; RR: 0.83, 95% CI 0.61-1.13; moderate certainty of evidence) and the 24-36 months progression rates (CHT: 4.4%, BCG: 7.6%, RR = 0.62, 95% CI 0.26-1.49; low certainty of evidence). There were also no significant differences in grade 1-2 adverse events (CHT group: 59.9%, BCG group 54.5%; RR = 1.10, 95% CI 0.93-1.30; moderate certainty of evidence) and grade 3 or above adverse events (CHT group: 23.2%, BCG group 22.5%; RR = 0.99, 95% CI 0.69-1.43; low certainty of evidence). Conclusions: Intravesical CHT had equivalent oncological outcomes and similar safety profile when compared to BCG maintenance therapy for patients with intermediate- and high-risk NMIBC. CHT is a possible alternative treatment in the times of BCG shortage.

How to manage patients with suspected upper tract urothelial carcinoma in the pandemic of COVID-19?

BACKGROUND: The pandemic of COVID-19 has disrupted the clinical pathway for patients with suspected upper tract urothelial carcinoma (UTUC). This aims to investigate the optimal management of UTUC during the pandemic by determining 1) Whether a three-month delay of RNU leads to worsened overall survival, 2) Whether radical nephroureterectomy (RNU) can be performed without prior diagnostic ureteroscopy (URS). METHODS: Consecutive patients with RNU performed for suspected UTUC in four hospitals in Hong Kong and Taiwan were included. Patients with histologically proven UTUC and with RNU performed within one year were dichotomized into early (≤3 months) and delayed (>3 months) RNU groups. Diagnostic performances of predictive models based on pre-URS factors (gross haematuria, suspicious or malignant urine cytology, and filling defect or contrast-enhancing mass on computed tomography), with or without URS, were analysed using receiver operating characteristics and area under curve (AUC). Overall survival was analysed using Kaplan-Meier method and multivariate Cox regression analysis. RESULTS: Between 2000 and 2019, 665 patients underwent RNU, and 491 of them had prior diagnostic URS. The early RNU group had a better overall survival (P = 0.015). Early RNU was associated with a better overall survival upon multivariate analysis (HR 1.55, 95% CI 1.03-2.33, P = 0.035). Large tumour size, multi-focal tumour, T2 or above disease, and positive nodal status were associated with a poorer overall survival. A combination of any 2 out of the 3 pre-URS factors achieved a positive predictive value of 99.5 to 100%. Presence of all 3 pre-URS factors achieved an AUC of 0.851 with URS, and AUC of 0.809 without URS. CONCLUSIONS: A delay of RNU for over 3 months was associated with poorer overall survival and has to be avoided despite the current COVID-19. We can also consider direct RNU based on clinical factors alone. This also avoids URS hospitalization and expedites the clinical pathway of UTUC.

Perioperative Outcomes of Robot-Assisted Radical Cystectomy with Intracorporeal Versus Extracorporeal Urinary Diversion.

PURPOSE: This study was designed to investigate and compare the perioperative outcomes of intracorporeal urinary diversion (ICUD) versus extracorporeal urinary diversion (ECUD) following robotic-assisted radical cystectomy (RARC) in patients with localized bladder cancer from the Asian Robot-Assisted Radical Cystectomy (RARC) Consortium. METHODS: The Asian RARC registry was a multicenter registry involving nine centers in Asia. Consecutive patients who underwent RARC were included. Patient and disease characteristics, intraoperative details, and perioperative outcomes were reviewed and compared between the ICUD and ECUD groups. Postoperative complications were the primary outcomes, whereas secondary outcomes were the estimated blood loss and the duration of hospitalization. Multivariate regression analyses were performed to adjust potential confounders. RESULTS: From 2007 to 2020, 556 patients underwent RARC; 55.2% and 44.8% had ICUD and ECUD, respectively. ICUD group had less estimated blood loss (423.1 ± 361.1 vs. 541.3 ± 474.3 mL, p = 0.002) and a shorter hospital stay (15.7 ± 12.3 vs 17.8 ± 11.6 days, p = 0.042) than the ECUD group. Overall complication rates were similar between the two groups. Upon multivariate analysis, ICUD was associated with less estimated blood loss (Regression coefficient: - 143.06, 95% confidence interval [CI]: - 229.60 to - 56.52, p = 0.001) and a shorter hospital stay (Regression coefficient: - 2.37, 95% CI: - 4.69 to - 0.05, p = 0.046). In addition, ICUD was not associated with any increased risks of minor, major, and overall complications. CONCLUSIONS: RARC with ICUD was safe and technically feasible with similar postoperative complication rates as ECUD, with additional benefits of reduced blood loss and a shorter hospitalization.

A Quantitative Analysis Investigating the Prevalence of "Manels" in Major Urology Meetings.

BACKGROUND: Female representation in urological meetings is important for gender equity. OBJECTIVE: Our objective was to examine the prevalence of "manels" or all-male speaking panels at urological meetings. DESIGN, SETTING, AND PARTICIPANTS: Urology meetings organized by major urological associations/societies from December 2019 to November 2020 were reviewed. Meeting information and details of the faculty were retrieved. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were: (1) the percentage of male faculty in all included sessions and (2) the overall proportion of manels. We made further comparisons between manel and multigender sessions. Male and female faculty were stratified by quartiles of publications, citations, and H-index, and their mean numbers of sessions were compared. RESULTS AND LIMITATIONS: Among 285 meeting sessions, 181 (63.5%) were manels. The mean percentage of male faculty was 86.9%. Male representation was very high in urology meetings for most disciplines and urological associations/societies, except for female urology meeting sessions and those organized by the International Continence Society. Nonmanel sessions had higher numbers of chairs/moderators (p = 0.027), speakers (p < 0.001), and faculty (p < 0.001) than manel sessions. A total of 1037 faculty members were included, and 900 of them (86.8%) were male. Male faculty had longer mean years of practice (23.8 vs 17.7 yr, p < 0.001) and was more likely to include professors (43.2% vs 17.5%, p < 0.001) than female faculty. Male faculty within the first quartile (ie, lower quartile) of publications and H-index had a significantly higher number of sessions than female faculty within the same quartile. CONCLUSIONS: Our study showed that manels are prevalent in urology meetings. There is evidence showing that males received more opportunities than females. A huge gender imbalance exists in urology meetings; urological associations and societies should actively strive for greater gender parity. PATIENT SUMMARY: Women are under-represented in urology meetings. Urological associations and societies should play an active role to ensure a more balanced gender representation.

The use of artificial intelligence for the diagnosis of bladder cancer: a review and perspectives.

PURPOSE OF REVIEW: White light cystoscopy is the current standard for primary diagnosis and surveillance of bladder cancer. However, cancer changes can be subtle and may be easily missed. With the advancement of deep learning (DL), image recognition by artificial intelligence (AI) proves a high accuracy for image-based diagnosis. AI can be a solution to enhance bladder cancer diagnosis on cystoscopy. RECENT FINDINGS: An algorithm that classifies cystoscopic images into normal and tumour images is essential for AI cystoscopy. To develop this AI-based system requires a training dataset, an appropriate type of DL algorithm for the learning process and a specific outcome classification. A large data volume with minimal class imbalance, data accuracy and representativeness are pre-requisite for a good dataset. Algorithms developed during the past two years to detect bladder tumour achieved high performance with a pooled sensitivity of 89.7% and specificity of 96.1%. The area under the curve ranged from 0.960 to 0.980, and the accuracy ranged from 85.6 to 96.9%. There were also favourable results in the various attempts to enhance detection of flat lesions or carcinoma-in-situ. SUMMARY: AI cystoscopy is a possible solution in clinical practice to enhance bladder cancer diagnosis, improve tumour clearance during transurethral resection of bladder tumour and detect recurrent tumours upon surveillance.

Immune Checkpoints Inhibitors and Chemotherapy as First-Line Treatment for Metastatic Urothelial Carcinoma: A Network Meta-Analysis of Randomized Phase III Clinical Trials.

Immune checkpoints inhibitors (ICIs) were considered as second-line treatments in metastatic urothelial carcinoma (mUC) based on better survival benefit and safety profile than chemotherapy (CTX). We aimed to assess different ICIs regimens in the efficacy and safety for front-line treatments in mUC patients. A comprehensive literature search was performed and Phase II-III randomized controlled trials (RCTs) on ICIs for patients with mUC were included. The outcome was evaluated by overall survival (OS), progression of free survival (PFS), objective response rate (ORR), and grade 3-5 adverse events. Network meta-analysis was used to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were applied to rank the included treatments for each outcome. Results: The survival benefit of a single ICI was non-inferiority to chemotherapy (CTX). Although no superior effects were indicated, combination therapy (either ICIs plus CTX or ICIs plus ICIs) presented better OS compared with CTX alone. In terms of PFS, combination therapy produced a noticeable benefit over CTX. Regarding the SUCRA ranking, atezolizumab plus CTX was associated with the best ranking for OS and pembrolizumab plus CTX was the best in PFS. In terms of safety, a single ICI had better safety profile than CTX and combination therapy had a similar risk of grade 3-5 adverse events with CTX. Conclusions: Our NMA results revealed that combination therapy has better ranking compared with monotherapy in OS and acceptable AEs. ICIs alone present non-inferior OS but a lower incidence of AEs compared with CTX.

Feminine gender norms and syndemic harmful drinking, sexual violence, and sexually transmitted infections among Black women at risk for HIV.

BACKGROUND: This study examined the associations between feminine gender ideologies (i.e., socially constructed attitudes and beliefs of women's appropriate behavior and roles) and the syndemic comorbidities of harmful alcohol use, sexual violence, and sexually transmitted infections (STI), which disproportionately affect Black women. METHODS: Black women, aged 18-44 (n = 305) were recruited from STI clinics in Baltimore, MD into a retrospective cohort study. A survey assessed feminine gender ideologies using a measure of hyperfemininity and sexual hyperfemininity (subscale of sexual domains), harmful drinking (AUDIT), lifetime STI (Y/N and count), and syndemic burden (no burden [0-1 morbidity] and syndemic burden [2-3 comorbidities]). Multivariable regression models identified correlates of harmful drinking, STI, and syndemic burden. The analytic sample included (n = 231) women with complete data. RESULTS: Nearly half of our sample reported high hyperfemininity and high sexual hyperfemininity, 23% reported harmful drinking, 39% experienced sexual violence as an adult, and 74% reported a lifetime STI. High sexual hyperfemininity (Adjusted Odds Ratio [AOR] = 1.94, 95% Confidence Interval [CI]: 1.00-3.76) and sexual violence (AOR = 2.82, 95%CI: 1.43-5.58) were associated with greater odds of harmful drinking. Experiencing sexual violence in adulthood was associated with an increased count of lifetime STIs (Adjusted Incidence Rate Ratio [AIRR] = 1.33, 95%CI: 1.06-1.68). Syndemic burden affected 41% of our sample. High sexual hyperfemininity was associated with experiencing syndemic burden in unadjusted models (OR = 1.98, 95%CI: 1.16-3.37), but was not significant after controlling for confounders. CONCLUSIONS: Interventions to reduce harmful drinking and STIs among Black women in the U.S. should address sexual gender ideologies and sexual violence.

Clear cell carcinoma of the urinary bladder: a systematic review.

PURPOSE: We conducted a systematic review of the literature on primary clear cell carcinoma (CCC) of the urinary bladder. METHODS: A literature search using keywords and MeSH terms related to "clear cell carcinoma", "clear cell adenocarcinoma", "mesonephroma" and "urinary bladder" in EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials was performed. A manual search was performed with web-based search engine Google Scholar. Reference lists of the included studies were screened for additional articles. Articles up till 16th July 2020 were retrieved. Observational human studies on primary CCC in urinary bladder with English full-text were included for further analysis. RESULTS: 904 articles were identified and 44 articles were included for further analysis. Data including clinical features, tumour characteristics, treatment and oncological outcomes were reviewed. There were 70 patients (44 females and 26 males) reported in literatures and included in this review. Gross haematuria was the most common presentation (79.7%), followed by irritative urinary symptoms (47.5%). Regarding the histology, tubulocystic pattern is the most common histologic pattern (49.1%), and 52.6% had muscle invasion. Most cases were CK7 (96.6%) and CK20 (88.9%) positive. CA125 (96%) was commonly positive, indicating its potential origin from mullerian duct. Most patients received surgery (95.5%) as primary treatment. However, the oncological outcomes were unsatisfactory with a 2-year survival rate of 60.0%. CONCLUSION: Clear cell carcinoma is an uncommon subtype of bladder cancer which can be diagnosed by histology and immunohistochemical staining result. The majority of patients presented with muscle invasion and had a poor survival despite aggressive treatment.

Clinically relevant factors associated with quantitative optical coherence tomography angiography metrics in deep capillary plexus in patients with diabetes.

BACKGROUND: To test clinically relevant factors associated with quantitative artifact-free deep capillary plexus (DCP) metrics in patients with diabetes mellitus (DM). METHODS: 563 eligible eyes (221 with no diabetic retinopathy [DR], 135 with mild DR, 130 with moderate DR, and 77 with severe DR) from 334 subjects underwent optical coherence tomography-angiography (OCT-A) with a swept-source OCT (Triton DRI-OCT, Topcon, Inc., Tokyo, Japan). Strict criteria were applied to exclude from analysis those DCP images with artifacts and of poor quality, including projection artifacts, motion artifacts, blurriness, signal loss, B-scan segmentation error, or low-quality score. A customized MATLAB program was then used to quantify DCP morphology from the artifact-free DCP images by calculating three metrics: foveal avascular zone (FAZ), vessel density (VD), and fractal dimension (FD). RESULTS: 166 (29.5%) eyes were excluded after quality control, leaving in the analysis 397 eyes (170 with no DR, 101 with mild DR, 90 with moderate DR, 36 with severe DR) from 250 subjects. In the multiple regression models, larger FAZ area was associated with more severe DR (ß = 0.687; p = 0.037), shorter axial length (AL) (ß = - 0.171; p = 0.003), thinner subfoveal choroid thickness (ß = - 0.122; p = 0.031), and lower body mass index (BMI) (ß = - 0.090; p = 0.047). Lower VD was associated with more severe DR (ß = - 0.842; p = 0.001), shorter AL (ß = 0.107; p = 0.039), and poorer visual acuity (VA) (ß = - 0.133; p = 0.021). Lower FD was associated with more severe DR (ß = - 0.891; p < 0.001) and with older age (ß = - 0.142; p = 0.004). CONCLUSIONS: Quantitative artifact-free DCP metrics are associated with VA, DR severity, AL, subfoveal choroidal thickness, age, and BMI in diabetic patients. The effects of ocular and systemic factors should be considered for meaningful interpretations of DCP changes in DM patients.

A diaminocyclohexyl analog of SNS-032 with improved permeability and bioavailability properties.

The identification of a selective CDK2, 7, 9 inhibitor 4 with improved permeability is described. Compound 4 exhibits comparable CDK selectivity profile to SNS-032, but shows improved permeability and higher bioavailability in mice.

Modifications of the isonipecotic acid fragment of SNS-032: analogs with improved permeability and lower efflux ratio.

Modifications of the isonipecotic acid fragment of SNS-032 results in analogs which are more permeable and lower effluxed than SNS-032. The enantiomerically pure synthesis and the in vivo profile of analog 20 is described.

Maternal glutaric acidemia, type I identified by newborn screening.

We report two women with glutaric acidemia type I in whom the diagnosis was unsuspected until a low carnitine level was found in their newborn children. Both mothers had low carnitine in plasma. In the first, organic acid analysis was only done after fibroblast studies revealed normal carnitine uptake. Having learned from the first family, organic acid analysis was done immediately in the mother of family 2. In both, the plasma acylcarnitine profile was normal but both excreted the metabolites typical of their disorder. One of the women was a compound heterozygote for distinct mutations in the glutaric acid dehydrogenase gene, whereas the second was either homozygous or hemizygous for a mutation in Exon 6 of the gene.