Temporal Trends in Treatment and Outcomes of Endometrial Carcinoma in the United States, 2005-2020.

Endometrial cancer has continued to see a rising incidence in the US over the years. The main aim of this study was to assess current trends in patients' characteristics and outcomes of treatment for endometrial carcinoma over 16 years. A dataset from the National Cancer Database (NCDB) for patients diagnosed with endometrial carcinoma from 2005 to 2020 was used in this retrospective, case series study. The main outcomes and measures of interest included tumor characteristics, hospitalization, treatments, mortality, and overall survival. Then, 569,817 patients who were diagnosed with endometrial carcinoma were included in this study. The mean (SD) age at diagnosis was 62.7 (11.6) years, but 66,184 patients (11.6%) were younger than 50 years, indicating that more patients are getting diagnosed at younger ages. Of the patients studied, 37,079 (6.3%) were Hispanic, 52,801 (9.3%) were non-Hispanic Black, 432,058 (75.8%) were non-Hispanic White, and 48,879 (8.6%) were other non-Hispanic. Patients in the 4th period from 2017 to 2020 were diagnosed more with stage IV (7.1% vs. 5.2% vs. 5.4% vs. 5.9%; p < 0.001) disease compared with those in the other three periods. More patients with severe comorbidities (Charlson Comorbidity Index score of three) were seen in period 4 compared to the first three periods (3.9% vs. ≤1.9%). Systemic chemotherapy use (14.1% vs. 17.7% vs. 20.4% vs. 21.1%; p < 0.001) and immunotherapy (0.01% vs. 0.01% vs. 0.2% vs. 1.1%; p < 0.001) significantly increased from period 1 to 4. The use of laparotomy decreased significantly from 42.1% in period 2 to 16.7% in period 4, while robotic surgery usage significantly increased from 41.5% in period 2 to 64.3% in period 4. The 30-day and 90-day mortality decreased from 0.6% in period 1 to 0.2% in period 4 and 1.4% in period 1 to 0.6% in period 4, respectively. Over the period studied, we found increased use of immunotherapy, chemotherapy, and minimally invasive surgery for the management of endometrial cancer. Overall, the time interval from cancer diagnosis to final surgery increased by about 6 days. The improvements observed in the outcomes examined can probably be associated with the treatment trends observed.

Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements.

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices.

Understanding Barriers to Human Papillomavirus Vaccination among Parents of 9-10-Year-Old Adolescents: A Qualitative Analysis.

HPV vaccination rates remain low among US adolescents, with only 54% completing the series in 2019. The vaccine is recommended at age 11-12 but can be given as early as age 9. Although it has been found that offering the vaccine earlier improves completion rates by age 13, parents remain reluctant to allow their younger children to initiate this vaccine. The purpose of this study was to better understand parental beliefs regarding receipt of the HPV vaccine among their children at ages 9-10. A 40 min phone interview was completed with 21 participants who were asked about their vaccine viewpoints. Even after receiving one-on-one education from a patient navigator, many caretakers expressed inadequate knowledge of the HPV vaccine and limited exposure to both positive and negative influences. The biggest concern was vaccine side effects, often resulting from a lack of medical understanding. Most parents were reluctant to vaccinate their children at a school-based clinic or pharmacy and believed that the government should not mandate HPV vaccination for public school attendance. Our study provides insight into parental beliefs and attitudes about HPV vaccination at age 9-10 years and barriers that need to be addressed.

Immunogenicity of 2 or 3 Doses of 9vHPV Vaccine in U.S. Female Individuals 15 to 26 Years of Age.

Immunogenicity of Two or Three Doses of 9vHPV VaccineThis noninferiority trial examined two versus three doses of 9-valent human papillomavirus (9vHPV) vaccine in individuals 15 to 26 years of age in the United States. In an unplanned interim analysis of female participants, two doses of 9vHPV vaccine appeared to elicit similar rates of seroconversion and antibody titers for each of the nine HPV genotypes to three doses at 1 month postvaccination.

Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention.

Importance: The current method of BRCA testing for breast and ovarian cancer prevention, which is based on family history, often fails to identify many carriers of pathogenic variants. Population-based genetic testing offers a transformative approach in cancer prevention by allowing for proactive identification of any high-risk individuals and enabling early interventions. Objective: To assess the lifetime incremental effectiveness, costs, and cost-effectiveness of population-based multigene testing vs family history-based testing. Design, Setting, and Participants: This economic evaluation used a microsimulation model to assess the cost-effectiveness of multigene testing (BRCA1, BRCA2, and PALB2) for all women aged 30 to 35 years compared with the current standard of care that is family history based. Carriers of pathogenic variants were offered interventions, such as magnetic resonance imaging with or without mammography, chemoprevention, or risk-reducing mastectomy and salpingo-oophorectomy, to reduce cancer risk. A total of 2000 simulations were run on 1 000 000 women, using a lifetime time horizon and payer perspective, and costs were adjusted to 2022 US dollars. This study was conducted from September 1, 2020, to December 15, 2023. Main Outcomes and Measures: The main outcome measure was the incremental cost-effectiveness ratio (ICER), quantified as cost per quality-adjusted life-year (QALY) gained. Secondary outcomes included incremental cost, additional breast and ovarian cancer cases prevented, and excess deaths due to coronary heart disease (CHD). Results: The study assessed 1 000 000 simulated women aged 30 to 35 years in the US. In the base case, population-based multigene testing was more cost-effective compared with family history-based testing, with an ICER of $55 548 per QALY (95% CI, $47 288-$65 850 per QALY). Population-based multigene testing would be able to prevent an additional 1338 cases of breast cancer and 663 cases of ovarian cancer, but it would also result in 69 cases of excess CHD and 10 excess CHD deaths per million women. The probabilistic sensitivity analyses show that the probability that population-based multigene testing is cost-effective was 100%. When the cost of the multigene test exceeded $825, population-based testing was no longer cost-effective (ICER, $100 005 per QALY; 95% CI, $87 601-$11 6323). Conclusions and Relevance: In this economic analysis of population-based multigene testing, population-based testing was a more cost-effective strategy for the prevention of breast cancer and ovarian cancer when compared with the current family history-based testing strategy at the $100 000 per QALY willingness-to-pay threshold. These findings support the need for more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management.

One dose versus two doses of COVID-19 vaccine for the prevention of breakthrough infections among people previously infected with SARS-Cov-2.

Studies have suggested the effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 reinfection among those previously infected. However, it is not yet clear if one dose of the vaccine is enough to prevent breakthrough infections compared to two doses. Using data from Optum deidentified COVID-19 Electronic Health Record (EHR) data set, we assessed breakthrough infection risks in individuals previously infected, comparing those with one vaccine dose to those with two doses. Propensity scores were applied to mitigate confounding factors. Follow-up spanned 6 months, beginning 2 weeks postvaccination. Among 213 845 individuals, those receiving one vaccine dose had a significantly higher breakthrough infection risk than the two-dose group (HR 1.69, 95% CI 1.54-1.85). This pattern was observed across genders, racial/ethnic groups, age categories, and vaccine types. This study reveals a substantial disparity in the risk of breakthrough infections between individuals receiving one versus two doses of the COVID-19 vaccine, suggesting that a single dose may not provide adequate protection against reinfection.

Pilot Study to Investigate the Use of In-Clinic Sensing to Identify Optimal Stimulation Parameters for Deep Brain Stimulation Therapy in Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) programming is time intensive. Recent advances in sensing technology of local field potentials (LFPs) may enable improvements. Few studies have compared the use of this technology with standard of care. OBJECTIVE/HYPOTHESIS: Sensing technology of subthalamic nucleus (STN) DBS leads in Parkinson's disease (PD) is reliable and predicts the optimal contacts and settings as predicted by clinical assessment. MATERIALS AND METHODS: Five subjects with PD (n = 9 hemispheres) with bilateral STN DBS and sensing capable battery replacement were recruited. An LFP sensing review of all bipolar contact pairs was performed three times. Contact with the maximal beta peak power (MBP) was then clinically assessed in a double-blinded fashion, and five conditions were tested: 1) entry settings, 2) off stimulation, 3) MBP at 30 µs, 4) MBP at 60 µs, and 5) MBP at 90 µs. RESULTS: Contact and frequency of the MBP power in all hemispheres did not differ across sessions. The entry settings matched with the contact with the MBP power in 5 of 9 hemispheres. No clinical difference was evident in the stimulation conditions. The clinician and subject preferred settings determined by MBP power in 7 of 9 and 5 of 7 hemispheres, respectively. CONCLUSIONS: This study indicates that STN LFPs in PD recorded directly from contacts of the DBS lead provide consistent recordings across the frequency range and a reliably detected beta peak. Furthermore, programming based on the MBP power provides at least clinical equivalence to standard of care programming with STN DBS.

Adaptations of an Effective Evidence-Based Pediatric Weight Management Intervention.

Current childhood obesity treatment programs do not address medically underserved populations or settings where all members of an interdisciplinary team may not exist-either within one organization or within the community. In this paper, we describe the use of a community-academic partnership to iteratively adapt Epstein's Traffic Light Diet (TLD), into Building Healthy Families (BHF), a community-placed evidence-based pediatric weight management intervention (PWMI) and evaluate its effectiveness in reducing BMI z scores. Nine cohorts of families completed BHF. Participants included children aged 6-12 years with obesity (M = 9.46, SD = 1.74). The Framework for Reporting Adaptations and Modifications-Expanded guided our classification of modifications across BHF cohorts. Using the FRAME reporting structure, the changes that were documented were (1) planned and occurred pre-implementation, (2) based on decisions from local stakeholders (e.g., school administrator, members of the implementation team), and (3) specific to changes in content and context-with a focus on implementation and potential for local scale-up. The nature of the adaptations included adding elements (whole of family approach), removing elements (calorie counting), and substituting elements (steps for minutes of physical activity). Across 9 cohorts, 84 families initiated the BHF program, 69 families successfully completed the 12-week program, and 45 families returned for 6-month follow-up assessments. Results indicated that the BMI z score in children was reduced by 0.31 ± 0.17 at 6 months across all cohorts. Reduction in BMI z score ranged from 0.41 in cohort 4 to 0.13 in cohort 5. Iterative adaptations to BHF were completed to improve the fit of BHF to the setting and participants and have contributed to a sustained community PWMI that adheres to the underlying principles and core elements of other evidence-based PWMIs. Monitoring adaptations and related changes to outcomes can play a role in long-term sustainability and effectiveness.

Incomplete HPV Vaccination among Individuals Aged 27-45 Years in the United States: A Mixed-Effect Analysis of Individual and Contextual Factors.

Background: In the United States, the human papillomavirus (HPV) vaccine is approved for use in individuals up to age 45. Individuals 15 years and older require three doses of the vaccine to complete the recommended dosing series. Incomplete HPV vaccination rates (i.e., one or two doses) among those over age 26, however, remain high. This study examined the independent effects of individual- and neighborhood-level factors on incomplete HPV vaccination rates in the United States (U.S.) among those aged 27-45 years. Methods: This retrospective cohort study used administrative data from Optum's de-identified Clinformatics® Data Mart Database to identify individuals aged 27-45 years who received one or more doses of HPV vaccine between July 2019 and June 2022. Multilevel multivariable logistic regression models were applied to the data on 7662 individuals identified as being fully or partially vaccinated against HPV, nested within 3839 neighborhoods across the U.S. Results: Approximately half of the patients in this study (52.93%) were not completely vaccinated against HPV. After adjusting for all other covariates in the final model, being older than 30 years old decreased the odds of not completing the HPV vaccine series. Participants living in South-region neighborhoods of the U.S. had enhanced odds of not completing the vaccine series compared with those residing in Northeast-region neighborhoods (aOR 1.21; 95% CrI 1.03-1.42). There was significant clustering of incomplete HPV vaccination rates at the neighborhood level. Conclusions: This study revealed that individual- and neighborhood-level factors were associated with the risk of not completing the HPV vaccine series among individuals aged 27-45 years in the U.S. Interventions to improve HPV vaccination series completion rates for this age group should take into consideration both individual and contextual factors.

Dementias Among Older Males and Females in the U.S. Medicare System With and Without HIV.

BACKGROUND: Despite the growing concern that people with HIV (PWH) will experience a disproportionate burden of dementia as they age, very few studies have examined the sex-specific prevalence of dementia, including Alzheimer disease and related dementias (AD/ADRD) among older PWH versus people without HIV (PWOH) using large national samples. METHODS: We constructed successive cross-sectional cohorts including all PWH aged 65+ years from U.S. Medicare enrollees and PWOH in a 5% national sample of Medicare data from 2007 to 2019. All AD/ADRD cases were identified by ICD-9-CM/ICD-10-CM diagnosis codes. Prevalence of AD/ADRD was calculated for each calendar year by sex-age strata. Generalized estimating equations were used to assess factors associated with dementia and calculate the adjusted prevalence. RESULTS: PWH had a higher prevalence of AD/ADRD, which increased over time compared with PWOH, especially among female beneficiaries and with increasing age. For example, among those aged 80+ years, the prevalence increased from 2007 to 2019 (females with HIV: 31.4%-44.1%; females without HIV: 27.4%-29.9%; males with HIV: 26.2%-33.3%; males without HIV: 21.0%-23.5%). After adjustment for demographics and comorbidities, the differences in dementia burden by HIV status remained, especially among older age groups. CONCLUSIONS: Older Medicare enrollees with HIV had an increased dementia burden over time compared with those without HIV, especially women and older subjects. This underscores the need to develop tailored clinical practice guidelines that facilitate the integration of dementia and comorbidity screening, evaluation, and management into the routine primary care of aging PWH.

Incidence of human papillomavirus-related cancers among males and females aged 15-34 years in the United States.

Postmarket surveillance of the incidence of human papillomavirus (HPV)-related cancers is essential to monitor the effectiveness of HPV vaccines. We directly compared HPV-related cancer incidences during the pre- and postvaccine era to assess the effects of HPV vaccination among vaccine-eligible age groups in the United States using data from the US Cancer Statistics database. The 5-year average annual incidence rates for HPV-related cancers decreased in 2015-2019 compared with 2002-2006 among females aged 15-24 years and 25-34 years. Overall, a decrease in young males was not observed, whereas males aged 25-34 years experienced a slight decline in oropharyngeal squamous cell carcinoma between 2005-2009 and 2015-2019. Incidence rates for HPV-related cancers statistically significantly decreased in the vaccine era compared with the prevaccine era among females aged 15-34 years, suggesting the potential early effects of the introduction of HPV vaccination in the United States.

Assessing incident depression among older people with and without HIV in U.S.

PURPOSE: Despite substantially higher prevalence of depression among people living with HIV/AIDS (PLWHA), few data exist on the incidence and correlates of depression in this population. This study assessed the effect of HIV infection, age, and cohort period on the risk of developing depression by sex among older U.S. Medicare beneficiaries. METHODS: We constructed a retrospective matched cohort using a 5% nationally representative sample of Medicare beneficiaries (1996-2015). People with newly diagnosed (n = 1309) and previously diagnosed (n = 1057) HIV were individually matched with up to three beneficiaries without HIV (n = 6805). Fine-Gray models adjusted for baseline covariates were used to assess the effect of HIV status on developing depression by sex strata. RESULTS: PLWHA, especially females, had higher risk of developing depression within five years. The relative subdistribution hazards (sHR) for depression among three HIV exposure groups differed between males and females and indicated a marginally significant interaction (p = 0.08). The sHR (95% CI) for newly and previously diagnosed HIV (vs. people without HIV) were 1.6 (1.3, 1.9) and 1.9 (1.5, 2.4) for males, and 1.5 (1.2, 1.8) and 1.2 (0.9, 1.7) for females. The risk of depression increased with age [sHR 1.3 (1.1, 1.5), 80 + vs. 65-69] and cohort period [sHR 1.3 (1.1, 1.5), 2011-2015 vs. 1995-2000]. CONCLUSIONS: HIV infection increased the risk of developing depression within 5 years, especially among people with newly diagnosed HIV and females. This risk increased with older age and in recent HIV epidemic periods, suggesting a need for robust mental health treatment in HIV primary care.

Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines.

The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-amplifying RNA (saRNA) vaccine followed by a UK authorised mRNA vaccine (BNT162b2) in individuals with and without previous COVID-19, and compared these responses with those who received an authorised vaccine alone. 35 subjects receiving saRNA (saRNA group) as part of the COVAC1 clinical trial and an additional 40 participants receiving an authorised SARS-CoV-2 vaccine only (non-saRNA group) were recruited. Antibody responses were measured by ELISA and a pseudoneutralisation assay for wildtype, Delta and Omicron variants. Cellular responses were measured by IFN-Æ´ ELISpot and an activation induced marker (AIM) assay. Approximately 50% in each group had previous COVID-19 prior to vaccination, confirmed by PCR or antibody positivity on ELISA. All of those who received saRNA subsequently received a full course of an authorised vaccine. The majority (83%) of those receiving saRNA who were COVID-19 naïve at baseline seroconverted following the second dose, and those with previous COVID-19 had an increase in antibody titres two weeks following saRNA vaccination (median 27-fold), however titres were lower when compared to mRNA vaccination. Two weeks following the 2nd authorised mRNA vaccine dose, binding and neutralising antibody titres were significantly higher in the saRNA participants with previous COVID-19, compared to non-saRNA, or COVID-19 naive saRNA participants. Cellular responses were again highest in this group, with a higher proportion of spike specific CD8+ than CD4+ T cells when compared to those receiving the mRNA vaccine only. These findings suggest an immunological benefit of increased antigen exposure, both from natural infection and vaccination, particularly evident in those receiving heterologous vaccination with saRNA and mRNA.

Impact assessment of a provider-targeted national vaccine messaging campaign on human papillomavirus vaccination rates among US adolescent males.

Initial uptake of the cancer-preventative human papillomavirus (HPV) vaccine in the US was slow, especially among adolescent males. To address this, the US Centers for Disease Control and Prevention (CDC) partnered with the Hager Sharp communications development company to launch a national campaign in 2015 to improve physician counseling and rebrand the vaccine as cancer prevention. In this study, we compared HPV vaccination rates among 13-17-year-old males before (2010-2014) and after (2015-2019) the CDC-Hager Sharp campaign using National Immunization Survey-Teen data to determine the potential impact of this campaign on improving vaccine uptake among adolescent males. Employing provider-verified vaccination data available for 49,644 males from 2010 to 2014 and 47,943 males from 2015 to 2019, we found that the adjusted prevalence ratios of 13-17-year-old males who initiated and completed the vaccine series increased approximately 5-fold between the 2010-2014 and 2015-2019 periods. Increases in post-campaign initiation/completion rates were greatest among respondents with mothers who were married or had attended college, respondents who lived in the Northeast or Midwest, and those from households with annual incomes > $75,000. Together, these data suggest that the campaign contributed to the observed increase in HPV vaccine uptake among adolescent males. Although sociodemographic disparities were identified, the greater improvement in vaccination rates observed among individuals with higher socio-demographic status may simply reflect their relatively poorer rates of initial vaccine uptake. Overall, the data suggest that provider-targeted campaigns can be a useful tool to boost vaccinations and should be considered for inclusion in future vaccination campaigns.

Trends in Oropharyngeal Cancer Incidence Among Adult Men and Women in the United States From 2001 to 2018.

Background: The human papillomavirus (HPV) vaccine was approved in 2006 and has been shown to decrease vaccine-related HPV types in the oropharynx. Its impact on the incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) has not been examined. We investigated the impact of HPV vaccination on the incidence of HPV-related OPSCC in the US among male and female adults from different age groups. Methods: The US Cancer Statistics 2001-2018 database and the National Cancer Institute (NCI)'s Surveillance Epidemiology and End Results (SEER) program were used in this study. OPSCC incidence was age-adjusted to the US standard population in 2000. Cause-specific 5-year survival probability was calculated using 60 monthly intervals in SEER*Stat software. Results: Incidence of HPV-related OPSCC was much higher in males than in females. Age-adjusted annual incidence of OPSCC was significantly lower in 2014-2018 than in 2002-2006 among males 20-44 years old (11.4 vs 12.8 per 1,000,000, rate ratio 0.89, 95% confidence interval 0.84-0.93) and among females 20-44 years old (3.0 vs 3.6 per 1,000,000, rate ratio 0.86, 95% confidence interval 0.78-0.95), but increased in both 45-64 year old and 65+ year old males and females. Joinpoint regression revealed a significant joint in the HPV-OPSCC incidence trend for 20-44-year-old males in 2008 at which time the incidence began to decrease. Except for 20-44 year old females (74.8% in 2002-2006 vs. 75.7% in 2009-2013, p=0.84), cancer-specific 5-year survivals significantly improved for males and females of all age groups. Conclusions: HPV-related OPSCC was much more common in males. Incidence of HPV-related OPSCC declined among young adults during the vaccination era compared with pre-vaccination era. Cancer-specific 5-year survival was significantly improved in young males but not in young females.

Vulvar Cancer Incidence in the United States and its Relationship to Human Papillomavirus Vaccinations, 2001-2018.

The human papillomavirus (HPV) vaccine was indicated for the prevention of vulvovaginal cancers in 2008, but its impact on the incidence of vulvar cancers within the US is unknown. To determine this, we conducted a secondary analysis of 88,942 vulvar cancer cases among women 20+ years old using the US Cancer Statistics 2001-2018 databases. Data were stratified by tumor behavior (in situ or invasive), age (20-44, 45-64, 65+ years old), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic), and US census region (Northeast, South, Midwest, West), and incidence rates and average annual percentage changes (AAPC) were calculated by group. Reversing previous trends, the incidence of vulvar carcinoma in situ significantly decreased between 2001 and 2018 among women from all age groups, races/ethnicities, and regions (combined AAPC,  -4.3; 95% confidence interval (CI), -4.7 to -3.8). The incidence of invasive vulvar squamous cell carcinoma decreased significantly among 20- to 44-year-old women (AAPC, -0.8; 95% CI, -1.3 to -0.3), but significantly increased among those 45 to 64 (AAPC, 2.3; 95% CI, 1.8-2.8) and 65+ years old (AAPC, 1.2; 95% CI, 1.1-1.4). Regardless of tumor behavior, incidence was highest among non-Hispanic Whites and the Midwest region. Overall, the significant declines in vulvar carcinoma in situ among all ages, as well as invasive vulvar cancer among younger women, are encouraging and complement other recent data suggesting HPV vaccinations are already reducing anal and cervical cancer incidence. Over time, further declines in vulvar carcinoma incidence are likely as uptake and completion rates of the HPV vaccine increase in the US. PREVENTION RELEVANCE: We found evidence that HPV vaccinations likely contributed to a decrease in the incidences of vulvar carcinoma in situ and invasive vulvar carcinoma among 20- to 44-year-old women between 2001 and 2018. Our data add to the growing evidence that HPV vaccinations are reducing the incidence of HPV-related anogenital cancers.

Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function.

T cells depend on the phosphatase CD45 to initiate T cell receptor signaling. Although the critical role of CD45 in T cells is established, the mechanisms controlling function and localization in the membrane are not well understood. Moreover, the regulation of specific CD45 isoforms in T cell signaling remains unresolved. By using unbiased mass spectrometry, we identify the tetraspanin CD53 as a partner of CD45 and show that CD53 controls CD45 function and T cell activation. CD53-negative T cells (Cd53-/-) exhibit substantial proliferation defects, and Cd53-/- mice show impaired tumor rejection and reduced IFNγ-producing T cells compared with wild-type mice. Investigation into the mechanism reveals that CD53 is required for CD45RO expression and mobility. In addition, CD53 is shown to stabilize CD45 on the membrane and is required for optimal phosphatase activity and subsequent Lck activation. Together, our findings reveal CD53 as a regulator of CD45 activity required for T cell immunity.

Incident depression among Medicare beneficiaries with disabilities and HIV.

OBJECTIVE: Despite disproportionally high prevalence of HIV and depression in persons with disabilities, no data have been published on the incidence and correlates of depression in Medicare beneficiaries with disabilities. We assessed the effect of HIV infection on developing depression in this population. DESIGN: We conducted a retrospective matched cohort study using a 5% sample of Medicare beneficiaries who qualified for disability coverage (1996-2015). METHODS: Beneficiaries with incident ( n  = 2438) and prevalent ( n  = 5758) HIV were individually matched with beneficiaries without HIV (HIV-, n  = 20 778). Fine-Gray models with death as a competing risk were used to assess the effect of HIV status, age, and cohort period on developing depression by sex strata. RESULTS: Beneficiaries with HIV had a higher risk of developing depression within 5 years ( P  < 0.0001). Sex differences were observed ( P  < 0.0001), with higher subdistribution hazard ratios (sHR) in males with HIV compared with controls. The risk decreased with age ( P  < 0.0001) and increased in recent years ( P  < 0.0001). There were significant age-HIV ( P  = 0.004) and period-HIV ( P  = 0.006) interactions among male individuals, but not female individuals. The sHR was also higher within the first year of follow-up among male individuals, especially those with incident HIV. CONCLUSION: Medicare enrollees with disabilities and HIV had an increased risk of developing depression compared to those without HIV, especially among males and within the first year of HIV diagnosis. The HIV-depression association varied by sex, age, and cohort period. Our findings may help guide screening and comprehensive management of depression among subgroups in this vulnerable population.

BRCA testing and testing results among women 18-65 years old.

Since the 1990 s discovery of BRCA1 and BRCA2 pathogenic variants in breast or ovarian cancer patients, genetic testing has been recommended as part of a targeted, individualized approach for cancer prevention and treatment in eligible individuals. The aim of this study was to assess trends in BRCA test rates and results among adult women aged 18 to 65 in the US between 2007 and 2017. Using Clinformatics© Data Mart (CDM) Electronic Health Records, we included 223,211 women 18-65 years old with documented BRCA testing results from 1/1/2007-9/30/2017. Positive results indicated the presence of pathogenic variantss. BRCA test rates increased significantly from 34 per 100,000 women in 2007 to 488 per 100,000 women in 2016 (APC 30.8, 95% confidence interval 26.6-35.1). Documented positive results decreased from 86.1% in 2007 to 78.0% in 2017(APC -0.6, 95% confidence interval -1.4-0.2). From 2007 to 2017, decreasing trends in the rates of documented positive results were observed among all three age groups (18-39, 40-54, and 55-65 years; largest in 40-54 group). In 2015-2017, women with positive test results were less likely to be non-Hispanic Whites, cancer patients, or living in the Northeast or an area with average household income ≥$50,000. Between 2007 and 2017, increasing use of BRCA testing for cancer prevention and treatment occurred, correlating to the observed decreasing documented positive test rate. The utilization of testing and corresponding test results differed significantly across races/ethnicities, suggestive of a divergent application of the same testing criteria.