Contribution of Syphilis to Adverse Pregnancy Outcomes in People Living With and Without HIV in South Brazil: 2008 to 2018.

BACKGROUND: Syphilis coinfection among pregnant people living with HIV (PLH) may worsen pregnancy outcomes. We evaluated the impact of syphilis coinfection on pregnancies in south Brazil. METHODS: Data were extracted from hospital records between January 1, 2008, and December 31, 2018. Preterm birth (PTB), low birth weight (LBW <2500 g), and a composite adverse infant outcome (AIO: HIV vertical transmission, loss to follow-up before HIV diagnosis, stillbirth, congenital syphilis) were evaluated among pregnancies without HIV and syphilis (PWOH + S), PLH monoinfection, syphilis monoinfection (PLS), and PLH with syphilis (PLH + S). RESULTS: Among 48,685 deliveries where patients were tested for HIV and syphilis, 1353 (2.8%) occurred in PLH; of these, 181 (13.4%) were HIV/syphilis coinfected (PLH + S). Among PLH, 2.4% of infants acquired HIV and 13.1% were lost to follow-up before HIV diagnosis. Among all PLS, 70.5% of infants acquired congenital syphilis. Across the cohort, 1.2% stillbirths/neonatal deaths occurred. Thirty-seven percent of PLH + S did not initiate antiretroviral therapy versus 15.4% of PLH monoinfection ( P < 0.001). Less than half (37.6%) of PLH + S had VDRL titers ≥1:16 compared with 21.7% of PLS only ( P < 0.001). Among PLH, syphilis coinfection and unknown/high VDRL titers (≥1:16) increased AIO risk more (adjusted relative risk [aRR], 3.96; 95% confidence interval [CI], 3.33-4.70) compared with low VDRL titers (≤1:8; aRR, 3.51; 95% CI, 2.90-4.25). Unsuppressed viremia (≥50 copies/mL) was associated with risk of PTB (aRR, 1.43; 95% CI, 1.07-1.92) and AIO (aRR, 1.38; 95% CI, 1.11-1.70) but not LBW. Lack of prenatal care was significant in predicting PTB and LBW in all PLH and PLS monoinfection. CONCLUSIONS: Syphilis coinfection worsens AIOs in all women and compounds negative effects of HIV infection during pregnancy. Effective syphilis treatment and HIV viral load suppression are paramount for optimal obstetric care.

The Impact of Homemade Laparoscopic Box Trainers on Medical Student Surgical Skills: A Randomized Control Pilot Study.

Objective: While instructional videos are commonly used in surgical education, there is a paucity of data on home laparoscopic box trainers. This pilot study evaluated impacts of augmenting instructional videos with these devices. Design: This was a randomized controlled pilot study evaluating laparoscopic surgical performance on the LapSim virtual surgical simulator before and after a 2 week curriculum of instructional videos alone (n = 8, 47.1%) vs videos plus a home laparoscopic box trainer (n = 9, 52.9%). The LapSim recorded mistake number, time, and instrument path length to complete each task. Participants completed surveys about their perceptions of surgery before and after the course. Participants: Preclinical medical students were recruited. Those with extensive surgical experience or did not complete the course were excluded. Results: For the box trainer group vs the videos alone group: mean change in mistakes was -10.0 (standard deviation [SD]:17.1) vs +.5 (SD:21.59) (P = .28); mean change in time was -433.24 (SD:304.67) seconds vs -366.16 (SD:240.10) seconds (P = .62); mean change in instrument path length was -4.27 (SD:4.38) meters vs -3.19 (SD:4.86) meters (P = .64). The box trainer group ranked "I feel as though surgery comes naturally" 1.58 points higher (95% confidence interval [CI]: .85, 2.32; P < .01) and "I am worried about being skilled at surgery" 1.26 points lower (95% CI: 2.29, -.24; P = .02) upon completing the study. The videos alone group reported no significant changes in survey responses. Conclusion: Home laparoscopic box trainers can generate confidence and reduce anxiety regarding surgical fields. This study provides a framework for future larger scale works.

The impact of expanding gynecologic oncology care to ovarian cancer patients in small cities and rural communities.

OBJECTIVE: Patients with ovarian cancer from smaller cities and rural communities face unique challenges in accessing comprehensive care. This study compares management strategies, outcomes, and access to care for patients in a small city and surrounding rural communities before and after establishing a full-time gynecologic oncology (GO) office. METHODS: A local tumor registry was used to identify patients diagnosed with ovarian cancer before and after a full-time GO office was established. Quantitative analyses were used to compare disease characteristics, management strategies, overall survival, and distance traveled for care between cohorts. RESULTS: Out of 381 patients, 171 women were diagnosed prior to establishing a full-time GO office (pre-GO) and 210 after (post-GO). Post-GO patients were more likely to undergo surgery by a GO specialist (97.1% versus 53.2%, p < 0.01), receive surgery locally (79.0% versus 43.3%, p < 0.01), and undergo complete lymph node dissection (63.3% versus 38.6%, p < 0.01). Patients treated with chemotherapy by GO increased from 10.3% pre-GO to 76.9% post-GO. 5-year survival rates were 33.8% versus 49.5% in the pre-GO and post-GO groups, respectively (p < 0.01). Median survival time increased from 30.8 months to 52.5 months from pre-GO to post-GO time periods. Distance patients traveled for surgery decreased from a mean of 47.9 miles pre-GO to 26.8 miles post-GO. CONCLUSION: After establishing a full-time GO office within a small city, local patients had significantly improved overall survival and access to care. These results highlight the benefit of expanding GO care into small cities with surrounding rural communities and may be used to address public health discrepancies for women across the country.

Empiric treatment for peritonsillar abscess: A single-center experience with medical therapy alone.

PURPOSE: Compare the use of medical therapy alone (MTA) with surgical therapy (ST) for the empiric treatment of peritonsillar abscess (PTA). MATERIALS AND METHODS: A consecutive cohort of patients treated for PTA at our institution from May 2013 to February 2019 was analyzed. Demographics, disease characteristics, management strategies, and treatment outcomes were compared between treatment groups. Primary outcomes included treatment failure, defined as the need for follow-up surgical intervention, and complications within 2-weeks of empiric treatment. RESULTS: 306 patients (72.7%) received MTA while 115 (27.3%) underwent ST. There was no significant difference in the rate of treatment failure between the MTA (7.2%) and ST (6.1%) groups (p = 0.879). Complications were rare in both groups (1.6% with MTA versus 0.9% with ST; p = 0.898). Dysphagia (p = 0.011), trismus (p = 0.045), larger abscesses (p < 0.001), and hospital admission (p < 0.001) were more common in the ST group. Corticosteroid prescriptions were a common component of MTA (53.3%) and less often used with ST (33.9%; p = 0.001). After adjusting for abscess size, there remained no significant difference in the rate of treatment failure between groups. Univariate analyses demonstrated no significant independent predictors of treatment failure including age, sex, race, tonsillitis history, smoking history, presenting signs and symptoms, abscess size, hospital admission, and corticosteroid prescriptions. CONCLUSIONS: MTA may be a safe and effective alternative to surgical drainage for the empiric treatment of PTA, warranting larger-scale prospective analyses. Abscess size did not appear to influence treatment failure; however, careful patient selection is likely to optimize treatment outcomes.

Ineffective penicillin treatment and absence of partner treatment may drive the congenital syphilis epidemic in Brazil.

BACKGROUND: Reducing congenital syphilis has been the focus of Brazilian health programs for decades, yet the cases continue to increase. Although health interventions have targeted HIV screening and treatment, syphilis management continues to be challenging. Syphilis during pregnancy may enhance the HIV maternal seroconversion risk. The potential factors fueling the syphilis epidemic were evaluated in south Brazil, an area of high HIV or syphilis endemicity. OBJECTIVE: We hypothesized that ineffective treatment because of a lack of partner treatment, late presentation to care, and reinfection of previously treated mothers were potential drivers of syphilis mother-to-child transmission. STUDY DESIGN: Data on women diagnosed with syphilis during pregnancy between January 1, 2008 and December 31, 2018 were obtained from a large urban hospital in Porto Alegre, Brazil. The patients were stratified into effective vs ineffective treatment groups according to the World Health Organization guidelines. Crude and adjusted risk ratios for the prediction of congenital syphilis and adverse fetal or neonatal outcomes were computed using Poisson regression. RESULTS: Nearly 56,000 pregnant women delivered over the 11-year period; 1541 (2.8%) had confirmed syphilis during pregnancy, with 934 (61%) receiving ineffective syphilis treatment because of late presentation and diagnosis, delayed treatment initiation, and loss to follow-up with no treatment recorded. Ineffective treatment was associated with maternal education, prenatal care, timing of syphilis diagnosis, venereal diseases research laboratory titers, and maternal HIV coinfection. On multivariate regression analysis, ineffective treatment (adjusted risk ratio, 4.52; 95% confidence interval, 2.35-8.69), absence of prenatal care (adjusted risk ratio, 9.31; 95% confidence interval, 3.77-23.0), syphilis diagnosis at delivery (adjusted risk ratio, 3.08; 95% confidence interval, 2.07-4.58), and maternal nontreponemal titers ≥1:64 (1.09-1.93) were associated with an increased risk of fetal loss. Ineffective treatment (adjusted risk ratio, 1.71; 95% confidence interval, 1.59-1.84), year of diagnosis 2014 to 2016 (adjusted risk ratio, 1.07; 95% confidence interval, 1.02-1.13), absence of prenatal care (adjusted risk ratio, 1.44; 95% confidence interval, 1.17-1.76), and maternal nontreponemal titers >1:4 were associated with an increased risk of congenital syphilis. Although partner treatment reduced the congenital syphilis risk (adjusted risk ratio, 0.60; 95% confidence interval, 0.55-0.66), only 31.8% of partners received treatment. Maternal HIV coinfection was not associated with an increased risk of fetal loss, low birthweight, preterm birth, congenital syphilis, or symptomatic neonatal infection. CONCLUSION: Public health initiatives promoting effective syphilis treatment in pregnancy, increased access to high-quality prenatal care, and partner treatment should be considered to reduce congenital syphilis.

Maternal HIV and syphilis are not syndemic in Brazil: Hot spot analysis of the two epidemics.

While the annual incidence of HIV diagnosis in pregnancy in Brazil remains relatively stable, rates of maternal syphilis increased over six-fold in the past decade. We hypothesized that maternal HIV and syphilis are two distinct epidemics. Data on all cases of maternal HIV or syphilis detected in pregnancy between January 1, 2010 to December 31, 2018 were requested from the Brazilian Ministry of Health. In order to evaluate how the epidemics evolved over the time period, ArcGIS software was used to generate spatiotemporal maps of annual rates of detection of maternal HIV and syphilis in 2010 and 2018. We utilized Euclidean-distance hot spot analysis to identify state-specific clusters in 2010 and 2018. From 2010 to 2018, there were 66,631 cases of maternal HIV, 225,451 cases of maternal syphilis, and 150,414 cases of congenital syphilis in Brazil. The state of Rio Grande do Sul had the highest rate of maternal HIV detection in both 2010 and 2018. Hot spots of maternal HIV were identified in the three most Southern states in both 2010 and 2018 (99% confidence, z-score >2.58, p <0.01). While syphilis incidence >30 per 1,000 live births in 2018 in four states, only the two coastal states of Rio de Janeiro and Espirito Santo in Southeastern Brazil were significant hot spots (90% confidence, z-score 1.65-1.95, p <0.10). Contrary to the general assumption, HIV and syphilis epidemics in Brazil are not syndemic in pregnant women. There is a spatial cluster of maternal HIV in the South, while syphilis is increasing throughout the country, more recently on the coast. Focusing on maternal HIV hot spots in the Southern states is insufficient to curtail the maternal and congenital syphilis epidemics throughout the country. New strategies, including ongoing hot spot analysis, are urgently needed to monitor, identify and treat maternal syphilis.

Failure to recognize Low non-treponemal titer syphilis infections in pregnancy May lead to widespread under-treatment.

OBJECTIVES: Rates of maternal syphilis have increased five-fold in Brazil in the past decade. While penicillin remains the only appropriate treatment for maternal syphilis, we hypothesized that low non-treponemal titers (<1:16) may lead to reduced penicillin treatment in Brazil. METHODS: Using Brazilian Ministry of Health data on women diagnosed with maternal syphilis between January 1, 2010, and December 31, 2018, we conducted a random-effects logistic regression model with a cluster correction at the state level to evaluate predictive factors of penicillin treatment. RESULTS: We observed yearly increases in cases of pregnant women with syphilis from 2010 to 2018. There was significant variation by state: 52,451 cases were reported in São Paulo, followed by 26,838 in Rio de Janeiro. Among 215,937 cases of maternal syphilis, 91·3% received penicillin. In the random-effects model, a non-treponemal titer ≥1:16 was associated with 1·44 higher odds of receiving penicillin (95% confidence interval [CI]: 1·391·48), and prenatal care was associated with a 2·12 increased odds of receiving penicillin (95% CI: 2·022·21). Although there is an association between the absence of prenatal care and inadequate treatment for syphilis, 83·2% of women in this cohort who did not receive penicillin were engaged in prenatal care. CONCLUSIONS: Providers may inappropriately exclude low non-treponemal titers and thereby fail to use penicillin treatment in maternal syphilis. While the cause of the maternal syphilis epidemic in Brazil is multifactorial, we believe our findings can be used to develop targeted interventions throughout Brazil as well as shape public health initiatives globally.

Predictors of SARS-CoV-2 Infection in Youth at a Large, Urban Healthcare Center in California, March-September 2020.

Objective: To understand which social, epidemiologic, and clinical risk factors are associated with SARS-CoV-2 infection in youth accessing care in a large, urban academic institution. Methods: We conducted a prospective cohort study with case-control analyses in youth who received testing for SARS-CoV-2 at our academic institution in Los Angeles during the first wave of the COVID-19 pandemic (March-September 2020). Results: A total of 27,976 SARS-CoV-2 assays among 11,922 youth aged 0-24 years were performed, including 475 youth with positive SARS-CoV-2 results. Positivity rate was higher among older, African American, and Hispanic/Latinx youth. Cases were more likely to be from non-English-speaking households and have safety-net insurance. Zip codes with higher proportion of Hispanic/Latinx and residents living under the poverty line were associated with increased SARS-CoV-2 cases. Youth were more likely to have positive results if tested for exposure (OR 21.5, 95% CI 14.6-32.1) or recent travel (OR 1.5, 95% CI 1.0-2.3). Students were less likely to have positive results than essential worker youth (OR 0.5, 95% CI 0.3-0.8). Patterns of symptom presentation varied significantly by age group; number of symptoms correlated significantly with age in SARS-CoV-2 cases (r = 0.030, p < 0.001). SARS-CoV-2 viral load did not vary by symptom severity, but asymptomatic youth had lower median viral load than those with symptoms (21.5 vs. 26.7, p = 0.009). Conclusions: Socioeconomic factors are important drivers of SARS-CoV-2 infection in youth. Presence of symptoms, exposure, and travel can be used to drive testing in older youth. Policies for school reopening and infection prevention should be tailored differently for elementary schools and universities.

Prospective cohort study of children exposed to hepatitis C virus through a pregnancy screening program.

OBJECTIVES: Porto Alegre, in south Brazil, has one of the highest hepatitis C virus (HCV) infection rates in the country (84.4 cases/100 000 in 2018). Prenatal screening of HCV, however, has not been routinely offered. METHODS: A longitudinal study of pregnant women with HCV and their infants was conducted between January 2014 and December 2018. Screening for HCV antibodies was offered to all women delivering at the study tertiary institution. HCV RT-PCR was performed if the woman was seropositive. Infants were followed prospectively. RESULTS: Among 18 953 pregnant women delivering infants during the study period, 17 810 were screened for HCV antibodies (93.9%) with 130 positive results (HCV seroprevalence 0.7%). HCV-RNA was detectable in 57/117 cases (48.7%). HCV viremia was associated with the use of injectable drugs (P = 0.03), inhaled/crack drug use (P = 0.02), having an HCV-seropositive partner, and ≥3 lifetime sexual partners (P < 0.01). Genotype 1 was most prevalent (68%) during pregnancy. Among 43 children with follow-up, six (13%) were HCV-infected (transmission rate 13.9%); 50% were infected with genotype 3. Two infants (33%) cleared their infection; the mothers had genetic polymorphisms associated with clearance. CONCLUSION: HCV vertical transmission was high in the study population, with HCV infection during pregnancy being vastly underdiagnosed. Public health efforts must focus on this vulnerable population for disease prevention and early treatment.

CTDSP1 inhibitor rabeprazole regulates DNA-PKcs dependent topoisomerase I degradation and irinotecan drug resistance in colorectal cancer.

Irinotecan specifically targets topoisomerase I (topoI), and is used to treat various solid tumors, but only 13-32% of patients respond to the therapy. Now, it is understood that the rapid rate of topoI degradation in response to irinotecan causes irinotecan resistance. We have published that the deregulated DNA-PKcs kinase cascade ensures rapid degradation of topoI and is at the core of the drug resistance mechanism of topoI inhibitors, including irinotecan. We also identified CTD small phosphatase 1 (CTDSP1) (a nuclear phosphatase) as a primary upstream regulator of DNA-PKcs in response to topoI inhibitors. Previous reports showed that rabeprazole, a proton pump inhibitor (PPI) inhibits CTDSP1 activity. The purpose of this study was to confirm the effects of rabeprazole on CTDSP1 activity and its impact on irinotecan-based therapy in colon cancer. Using differentially expressing CTDSP1 cells, we demonstrated that CTDSP1 contributes to the irinotecan sensitivity by preventing topoI degradation. Retrospective analysis of patients receiving irinotecan with or without rabeprazole has shown the effects of CTDSP1 on irinotecan response. These results indicate that CTDSP1 promotes sensitivity to irinotecan and rabeprazole prevents this effect, resulting in drug resistance. To ensure the best chance at effective treatment, rabeprazole may not be a suitable PPI for cancer patients treated with irinotecan.