Relationship of Heterologous Virus Responses and Outcomes in Hospitalized COVID-19 Patients.

The clinical trajectory of COVID-19 may be influenced by previous responses to heterologous viruses. We examined the relationship of Abs against different viruses to clinical trajectory groups from the National Institutes of Health IMPACC (Immunophenotyping Assessment in a COVID-19 Cohort) study of hospitalized COVID-19 patients. Whereas initial Ab titers to SARS-CoV-2 tended to be higher with increasing severity (excluding fatal disease), those to seasonal coronaviruses trended in the opposite direction. Initial Ab titers to influenza and parainfluenza viruses also tended to be lower with increasing severity. However, no significant relationship was observed for Abs to other viruses, including measles, CMV, EBV, and respiratory syncytial virus. We hypothesize that some individuals may produce lower or less durable Ab responses to respiratory viruses generally (reflected in lower baseline titers in our study), and that this may carry over into poorer outcomes for COVID-19 (despite high initial SARS-CoV-2 titers). We further looked at longitudinal changes in Ab responses to heterologous viruses, but found little change during the course of acute COVID-19 infection. We saw significant trends with age for Ab levels to many of these viruses, but no difference in longitudinal SARS-CoV-2 titers for those with high versus low seasonal coronavirus titers. We detected no difference in longitudinal SARS-CoV-2 titers for CMV seropositive versus seronegative patients, although there was an overrepresentation of CMV seropositives among the IMPACC cohort, compared with expected frequencies in the United States population. Our results both reinforce findings from other studies and suggest (to our knowledge) new relationships between the response to SARS-CoV-2 and Abs to heterologous viruses.

Increased Pediatric Respiratory Syncytial Virus Case Counts Following the Emergence of SARS-CoV-2 Can Be Attributed to Changes in Testing.

BACKGROUND: Respiratory syncytial virus (RSV) circulation dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The "immunity debt" hypothesis proposes that the RSV-naїve pediatric population increased during the period of low transmission. However, the evidence supporting this hypothesis is limited, and the role of changing testing practices in the perceived surge has not been comprehensively evaluated. METHODS: We conducted a multicenter, retrospective analysis of 342 530 RSV encounters and 980 546 RSV diagnostic tests occurring at 32 US pediatric hospitals in 2013-2023. We used interrupted time series analysis to estimate pandemic-associated changes in RSV patient and test volume and to quantify changes in the proportions of patients requiring hospitalization, intensive care, or mechanical ventilation. We quantified the fraction of the shifts in case counts and in the age of diagnosed patients attributable to changes in testing. RESULTS: RSV patient volume increased 2.4-fold (95% confidence interval [CI]: 1.7, 3.5) in 2021-2023 relative to the pre-pandemic phase and was accompanied by an 18.9-fold increase (95% CI: 15.0, 23.9) in RSV test volume. Shifts in patient volume and in patient age were largely attributable to increased testing. The proportions of patients with RSV that required hospitalization, intensive care, or mechanical ventilation declined significantly across all patient age groups. CONCLUSIONS: A surge in RSV testing, rather than in viral circulation, likely underlies the increased case counts observed in 2021-2023. These findings warrant a critical assessment of the immunity debt hypothesis and highlight the importance of considering the testing denominator when surveillance strategies are dynamic.

Effective early antiretroviral therapy in perinatal-HIV infection reduces subsequent plasma inflammatory profile.

BACKGROUND: The long-term immunologic effects of antiretroviral therapy (ART) in children with perinatally-acquired HIV (PHIV) have not been fully elucidated. Here, we investigated how the timing of ART initiation affects the long-term immune profile of children living with PHIV by measuring immunomodulatory plasma cytokines, chemokines, and adenosine deaminases (ADAs). METHODS: 40 PHIV participants initiated ART during infancy. 39 participant samples were available; 30 initiated ART ≤6 months (early-ART treatment); 9 initiated ART >6 months and <2 years (late-ART treatment). We compared plasma cytokine and chemokine concentrations and ADA enzymatic activities between early-ART and late-ART treatment 12.5 years later and measured correlation with clinical covariates. RESULTS: Plasma concentrations of 10 cytokines and chemokines (IFNγ, IL-12p70, IL-13, IL-17A, IL-IRA, IL-5, IL-6, and IL-9 as well as CCL7, CXCL10), ADA1, and ADA total were significantly higher in late-ART compared to early-ART treatment. Furthermore, ADA1 was significantly positively correlated with IFNγ, IL-17A, and IL-12p70. Meanwhile, total ADA was positively correlated with IFNγ, IL-13, IL-17A, IL-1RA, IL-6, and IL-12p70 as well as CCL7. CONCLUSIONS: Elevation of several pro-inflammatory plasma analytes in late-ART despite 12.5 years of virologic suppression compared to early-ART treatment suggests that early treatment dampens the long-term plasma inflammatory profile in PHIV participants. IMPACT: This study examines differences in the plasma cytokine, chemokine, and ADA profiles 12.5 years after treatment between early (≤6months) and late (>6 months and <2 years) antiretroviral therapy (ART) treatment initiation in a cohort of European and UK study participants living with PHIV. Several cytokines and chemokines (e.g., IFNγ, IL-12p70, IL-6, and CXCL10) as well as ADA-1 are elevated in late-ART treatment in comparison to early-ART treatment. Our results suggest that effective ART treatment initiated within 6 months of life in PHIV participants dampens a long-term inflammatory plasma profile as compared to late-ART treatment.

Precision Vaccine Adjuvants for Older Adults: A Scoping Review.

Older adults, defined as those ≥60 years of age, are a growing population vulnerable to infections including severe acute respiratory syndrome coronavirus 2. Although immunization is a key to protecting this population, immunosenescence can impair responses to vaccines. Adjuvants can increase the immunogenicity of vaccine antigens but have not been systematically compared in older adults. We conducted a scoping review to assess the comparative effectiveness of adjuvants in aged populations. Adjuvants AS01, MF59, AS03, and CpG-oligodeoxynucleotide, included in licensed vaccines, are effective in older human adults. A growing menu of investigational adjuvants, such as Matrix-M and CpG plus alum, showed promising results in early phase clinical trials and preclinical studies. Most studies assessed only 1 or 2 adjuvants and no study has directly compared >3 adjuvants among older adults. Enhanced preclinical approaches enabling direct comparison of multiple adjuvants including human in vitro modeling and age-specific animal models may derisk and accelerate vaccine development for older adults.

Advancing the Science of Vaccine Safety During the Coronavirus Disease 2019 (COVID-19) Pandemic and Beyond: Launching an International Network of Special Immunization Services.

Within 2 years after the start of the coronavirus disease 2019 (COVID-19) pandemic, novel severe acute respiratory syndrome coronavirus 2 vaccines were developed, rigorously evaluated in large phase 3 trials, and administered to more than 5 billion individuals globally. However, adverse events of special interest (AESIs) have been described post-implementation, including myocarditis after receipt of messenger RNA (mRNA) vaccines and thrombosis with thrombocytopenia syndrome after receipt of adenoviral vector vaccines. AESIs are rare (<1 to 10/100 000 vaccinees) and less frequent than COVID-19 complications, though they have associated morbidity and mortality. The diversity of COVID-19 vaccine platforms (eg, mRNA, viral vector, protein) and rates of AESIs both between and within platforms (eg, higher rate of myocarditis after mRNA-1273 vs BNT162b2 vaccines) present an important opportunity to advance vaccine safety science. The International Network of Special Immunization Services has been formed with experts in vaccine safety, systems biology, and other relevant disciplines to study cases of AESIs and matched controls to uncover the pathogenesis of rare AESIs and inform vaccine development.

Perinatally Human Immunodeficiency Virus-Infected Adolescents and Young Adults Demonstrate Distinct BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccine Immunogenicity.

BACKGROUND: Immunization of vulnerable populations with distinct immunity often results in suboptimal immunogenicity, durability, and efficacy. METHODS: Safety and immunogenicity profiles of BNT162b2 messenger RNA coronavirus disease 2019 (COVID-19) vaccine, among people living with human immunodeficiency virus (HIV), were evaluated in 28 perinatally HIV-infected patients under antiretroviral therapy (ART) and 65 healthy controls (HCs) with no previous history of COVID-19. Thus, we measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral and CD4+ T cell responses. Samples were collected before vaccination (baseline, day [D] 0), at the second dose (D21), and at 4 weeks (D28) and 6 months (D180) after D0. Proteomic profiles at D0 and D28 were assessed with a multiplexed proximity extension assay (Olink) on plasma samples. RESULTS: All HIV-infected patients mounted similar anti-SARS-CoV-2 humoral responses to those of HCs, albeit with lower titers of anti-trimeric S at D28 (P = .01). Only peripheral blood mononuclear cells of HIV-infected patients demonstrated at D28 an impaired ability to expand their specific (CD40L+) CD4+ T-cell populations. Similar humoral titers were maintained between the 2 groups at 6-months follow-up. We additionally correlated baseline protein levels to either humoral or cellular responses, identifying clusters of molecules involved in immune response regulation with inverse profiles between the 2 study groups. CONCLUSIONS: Responses of ART-treated HIV-infected patients, compared to those of HCs, were characterized by distinct features especially within the proteomic compartment, supporting their eligibility to an additional dose, similarly to the HC schedule.

Anxiety and depression in colorectal cancer survivors: Are there differences by sexual orientation?

OBJECTIVE: To examine sexual minority compared to heterosexual survivors' health-related anxiety, anxiety, and depression. METHODS: Four hundred and eighty eligible survivors participated in a telephone survey, which measured their anxiety and depression. These survivors were diagnosed with stage I, II, or III colorectal cancer an average of three years prior to the survey and were recruited from four cancer registries. As explanatory factors, we considered individual, social and contextual characteristics, prior psychological factors, psychological responses to cancer, and characteristics of cancer and its treatments. Using forward selection with generalized linear models or logistic regression models, we identified significant correlates for each outcome. RESULTS: Prior to adjusting for covariates, depression was similar for all survivors, while sexual minority survivors had worse health-related anxiety and anxiety compared to heterosexual survivors. After adjustment, these differences were no longer statistically significant. Individual, social and contextual characteristics, characteristics of cancer, and psychological responses to cancer explained 44% of the variance in anxiety and 60% of the variance in depression. CONCLUSION: There are modifiable factors associated with health-related and generalized anxiety as well as depression that can be changed to improve cancer survivorship among diverse survivors.

Health-related quality of life among colorectal cancer survivors of diverse sexual orientations.

BACKGROUND: The purpose of this study was to examine the health-related quality of life of sexual minority survivors in comparison with heterosexual survivors. METHODS: Four hundred eighty eligible survivors participated in a telephone survey that measured survivors' outcomes, which consisted of physical and mental quality of life and self-rated fair or poor health. These survivors were diagnosed with stage I, II, or III colorectal cancer an average of 3 years before the survey and were recruited from 4 cancer registries. Using forward selection with generalized linear models or logistic regression models, the authors considered 4 domains-personal factors, environmental factors, health condition characteristics, and body function and structure-as correlates for each survivorship outcome. RESULTS: The authors found that unadjusted physical quality of life and self-rated fair/poor health were similar for all survivors. Sexual minority survivors had poorer unadjusted mental quality of life in comparison with heterosexual survivors. After adjustments for covariates, this difference was no longer statistically significant. Three domains (personal factors, health condition characteristics, and body function and structure) explained colorectal cancer survivors' fair/poor health and 46% of the variance in physical quality of life, whereas 56% of the variance in mental quality of life was explained by personal factors, body function and structure, and environmental factors. CONCLUSIONS: This study has identified modifiable factors that can be used to improve cancer survivors' quality of life and are, therefore, relevant to ongoing efforts to improve the survivorship experience.

Predictive Value of Direct Disk Diffusion Testing from Positive Blood Cultures in a Children's Hospital and Its Utility in Antimicrobial Stewardship.

Accurate and early susceptibility results could reduce overuse of broad-spectrum antibiotics for empirical treatment of bacteremia. Direct disk diffusion testing (dDD) using nonstandardized inocula directly from blood cultures could facilitate earlier narrowing of antibiotics. To determine the predictive value of dDD compared with standardized antimicrobial susceptibility testing (AST), we performed a retrospective cohort study of 582 blood cultures from 495 pediatric patients with bacteremia. Positive and negative predictive value (PPV: number of isolates susceptible by both dDD and AST divided by the total number of isolates susceptible by dDD; NPV: number of isolates not susceptible [either intermediate or resistant] by both dDD and AST divided by the total number of isolates not susceptible by dDD), sensitivity, specificity, and 95% confidence interval were calculated for each bacterium-antibiotic combination. We evaluated the Antibiotic Spectrum Index of prescribed antibiotics to assess change in antibiotic prescribing after availability of Gram stain, dDD, and AST results. dDD results were available a median of 21 h before AST results. dDD had PPVs of ≥96% for most organism-antibiotic pairs, including 100% (CI 96 to 100%) for Staphylococcus aureus with oxacillin and 99% (CI 93 to 100%) for Enterobacterales with ceftriaxone. NPVs of dDD were variable and frequently lower than the PPV. Very major errors and major errors occurred in 31/5,454 (0.6%) and 231/5,454 (4.2%) organism-antibiotic combinations, respectively. Antibiotics were narrowed in 30% of cases after a dDD result and a further 25% of cases after AST result. dDD is highly predictive of susceptibility for many common organism-antibiotic combinations and provides actionable information one day earlier than standard susceptibility approaches. dDD has the potential to facilitate earlier deescalation to narrow-spectrum antibiotic treatment.

Ontogeny of plasma cytokine and chemokine concentrations across the first week of human life.

INTRODUCTION/BACKGROUND & AIMS: Early life is marked by distinct and rapidly evolving immunity and increased susceptibility to infection. The vulnerability of the newborn reflects development of a complex immune system in the face of rapidly changing demands during the transition to extra-uterine life. Cytokines and chemokines contribute to this dynamic immune signaling network and can be altered by many factors, such as infection. Newborns undergo dynamic changes important to health and disease, yet there is limited information regarding human neonatal plasma cytokine and chemokine concentrations over the first week of life. The few available studies are limited by small sample size, cross-sectional study design, or focus on perturbed host states like severe infection or prematurity. To characterize immune ontogeny among healthy full-term newborns, we assessed plasma cytokine and chemokine concentrations across the first week of life in a robust longitudinal cohort of healthy, full-term African newborns. METHODS: We analyzed a subgroup of a cohort of healthy newborns at the Medical Research Council Unit in The Gambia (West Africa; N = 608). Peripheral blood plasma was collected from all study participants at birth (day of life (DOL) 0) and at one follow-up time point at DOL 1, 3, or 7. Plasma cytokine and chemokine concentrations were measured by bead-based cytokine multiplex assay. Unsupervised clustering was used to identify patterns in plasma cytokine and chemokine ontogeny during early life. RESULTS: We observed an increase across the first week of life in plasma Th1 cytokines such as IFNγ and CXCL10 and a decrease in Th2 and anti-inflammatory cytokines such as IL-6 and IL-10, and chemokines such as CXCL8. In contrast, other cytokines and chemokines (e.g. IL-4 and CCL5, respectively) remained unchanged during the first week of life. This robust ontogenetic pattern did not appear to be affected by gestational age or sex. CONCLUSIONS: Ontogeny is a strong driver of newborn plasma-based levels of cytokines and chemokines throughout the first week of life with a rising IFNγ axis suggesting post-natal upregulation of host defense pathways. Our study will prove useful to the design and interpretation of future studies aimed at understanding the neonatal immune system during health and disease.

Assessing the relationship between symptoms and health care utilization in colorectal cancer survivors of different sexual orientations.

OBJECTIVE: The purpose of this study was to determine the association of physical and psychological symptoms with health care utilization in sexual minority and heterosexual colorectal cancer survivors. METHODS: Four hundred eighteen colorectal cancer survivors who were in remission an average of 3 years after their diagnosis were surveyed about their non-emergency health care visits during the preceding 3 months. Survivors reported whether they had experienced any of 21 symptoms common among colorectal cancer survivors in the past week. The relation between having had two or more health care visits in the preceding 3 months and symptoms experienced was assessed using logistic regression, controlling for cancer registry, sexual orientation, sex, age, race/ethnicity, income, and comorbidities. RESULTS: Of the survivors, 12% reported no symptoms, while 12% reported six or more symptoms. Sexual minority survivors reported significantly more weight concerns and more health-related and general anxiety as well as worse body image than heterosexual survivors. Frequent worrying about weight and experiencing sore skin around the anal area or stoma were the two symptoms that significantly contributed towards explaining survivors' increased health care utilization. CONCLUSION: Weight concerns, which are more common among the heaviest survivors, may prompt survivors to seek help from health care providers, which may lead to more frequent visits. On the other hand, some symptoms, despite their prevalence, had no relationship with the frequency of health care visits, raising questions about whether survivors share these concerns with providers.

Ethical climate in contemporary paediatric intensive care.

Ethical climate (EC) has been broadly described as how well institutions respond to ethical issues. Developing a tool to study and evaluate EC that aims to achieve sustained improvements requires a contemporary framework with identified relevant drivers. An extensive literature review was performed, reviewing existing EC definitions, tools and areas where EC has been studied; ethical challenges and relevance of EC in contemporary paediatric intensive care (PIC); and relevant ethical theories. We surmised that existing EC definitions and tools designed to measure it fail to capture nuances of the PIC environment, and sought to address existing gaps by developing an EC framework for PIC founded on ethical theory. In this article, we propose a Paediatric Intensive Care Ethical Climate (PICEC) conceptual framework and four measurable domains to be captured by an assessment tool. We define PICEC as the collective felt experience of interdisciplinary team members arising from those factors that enable or constrain their ability to navigate ethical aspects of their work. PICEC both results from and is influenced by how well ethical issues are understood, identified, explored, reflected on, responded to and addressed in the workplace. PICEC encompasses four, core inter-related domains representing drivers of EC including: (1) organisational culture and leadership; (2) interdisciplinary team relationships and dynamics; (3) integrated child and family-centred care; and (4) ethics literacy. Future directions involve developing a PICEC measurement tool, with implications for benchmarking as well as guidance for, and evaluation of, targeted interventions to foster a healthy EC.

Bacteriology of pediatric breast abscesses beyond the neonatal period.

BACKGROUND: Limited data exist regarding the presentation and bacteriology of nonneonatal pediatric breast abscess. OBJECTIVE: To determine the bacteriology and characteristic presentation of pediatric breast abscesses in a tertiary care center. METHODS: Cross-sectional study of patients age 1 month to 21 years admitted to a pediatric Emergency Department (ED) between 1996 and 2018 with a breast abscess. Patients with pre-existing conditions were excluded. Records were reviewed to determine demographics, history, physical exam findings, wound culture results, imaging and ED disposition. We used descriptive statistics to describe prevalence of different bacteria. RESULTS: We identified 210 patients who met study criteria. Median age was 13.6 years [IQR 6.6, 17.4], and 91% (191/210) were females. Ninety-two patients (43.8%) were 'pre-treated' with antibiotics prior to ED visit, and 33/210 (16%) were febrile. Ultrasound was obtained in 85 patients (40.5%), 69 patients had a single abscess and 16 had multiple abscesses. Most patients were treated with antibiotics and 100 had a surgical intervention, of these 89 had I&D and 11 a needle aspiration. Admission rate was 45%. Culture results were available for 75 (75%). Thirty-three (44%) had a negative culture, or grew non-aureus staphylococci or other skin flora. Culture were positive for MSSA 21 (28%), MRSA 13 (17%), Proteus mirabilis 2 (2.6%), Serratia 1 (1.3%). Other organisms include Gram-negative bacilli, group A Streptococcus and enterococcus. CONCLUSIONS: Non-neonatal pediatric breast abscess bacteriology is no different than data published on other skin abscesses. MRSA coverage should be considered based on local prevalence in skin infections.

Variation in hospital performance measures from the Turkey Ministry of Health.

BACKGROUND: The Turkish healthcare system has seen broad population-based improvements in expanded health insurance coverage and access to healthcare services. Hospital performance in this national system is understudied. We aimed to identify trends in hospital performance over time following implementation of the Health Transformation Program and describe how regional outcomes correlate with regional vital statistics. OBJECTIVE: We examine hospital performance data collected by the PHA from 2013 to 2015. We aim to identify the temporal variation in hospital performance for nearly 30 individual measures and to describe the relationship between hospital-level performance measures and regional vital statistics. METHODS: We conducted a retrospective cohort study of 674 public hospitals in Turkey using baseline data from 2013 and follow-up data from 2014-15 collected by the Turkish Statistical Institution and the Public Hospital Agency. We report demographic and socioeconomic data across 12 geographic regions and analyze 29 hospital-level performance measures across four domains: (i) health services; (ii) administrative services; (iii) financial services and (iv) quality measures. We examine temporal variation, and study correlation between performance measures and regional vital statistics. We fit mixed-effects linear regression models to estimate linear trend over time accounting for within-hospital residual correlation. We prepared our manuscript in accordance with guidelines set by the STROBE statement for cohort studies. RESULTS: During the 3 years of study period, 21 of 29 measures improved and 8 measures worsened. All but three measures demonstrated significant differences across regions of the country. Several measures, including inpatient efficiency, patient satisfaction and audit score, are associated with regional infant mortality and life expectancy. CONCLUSIONS: Evidence of temporal improvement in hospital-level performance may suggest some positive changes within the Turkish national healthcare system. Correlation of some measures with regional level health outcomes suggests a quality measurement strategy to monitor performance changes in the future. Although hospital-level functions have improved performance, the results of our study may help achieve further improvement for the health of the country's citizens.

Utility of Blood Cultures and Empiric Antibiotics in Febrile Pediatric Hemophilia Patients With Central Venous Access Devices.

BACKGROUND: Children with hemophilia frequently require long-term central venous access devices (CVADs) for regular infusion of factor products. Hemophilia patients are not immunocompromised, but the presence and use of CVADs are associated with infections including bacteremia. Currently, the utility of blood cultures in evaluation of the febrile hemophilia patient with an indwelling CVAD is unknown, nor is optimal empiric antibiotic use. METHODS: We performed a retrospective cross-sectional study of febrile immunocompetent hemophilia patients with CVADs presenting to a large academic urban pediatric emergency department from 1995 to 2017. We used a natural language processing electronic search, followed by manual chart review to construct the cohort. We analyzed rate of pathogen recovery from cultures of blood in subgroups of hemophilia patients, the pathogen profile, and the reported pathogen susceptibilities to ceftriaxone. RESULTS: Natural language processing electronic search identified 181 visits for fever among hemophilia patients with indwelling CVADs of which 147 cases from 44 unique patients met study criteria. Cultures of blood were positive in 56 (38%) of 147 patients (95% confidence interval, 30%-47%). Seventeen different organisms were isolated (10 pathogens and 7 possible pathogens) with Staphylococcus aureus and coagulase-negative Staphylococcus species as the most common. Thirty-four percent of isolates were reported as susceptible to ceftriaxone. Positive blood cultures were more common in cases involving patients with inhibitors (n = 71) versus those without (n = 76), odds ratio, 7.4 (95% confidence interval, 3.5-15.9). This was observed irrespective of hemophilia type. CONCLUSIONS: Febrile immunocompetent hemophilia patients with indwelling CVADs have high rates of bacteremia. Empiric antimicrobial therapy should be targeted to anticipated pathogens and take into consideration local susceptibility patterns for Staphylococcus aureus.

Transgender individuals' cancer survivorship: Results of a cross-sectional study.

BACKGROUND: Transgender individuals' cancer prevalence and transgender cancer survivors' health needs have received scarce attention. The current study compared transgender and cisgender individuals' cancer prevalence and described the health needs of transgender cancer survivors. METHODS: The authors used Behavioral Risk Factor Surveillance System data on 95,800 cisgender and transgender individuals who self-reported a cancer diagnosis. Using multiple logistic regression, they estimated cancer prevalence and calculated odds ratios with 95% confidence intervals of physical, psychological, overall health, and health behaviors of transgender survivors compared with cisgender survivors. RESULTS: After adjusting for confounders, transgender men had a significantly higher (>2-fold) number of cancer diagnoses compared with cisgender men, but not cisgender women. Cancer prevalence among gender nonconforming individuals and transgender women was not significantly different from that of cisgender men and cisgender women. Gender nonconforming survivors had significantly greater physical inactivity, heavy episodic alcohol use, and depression compared with cisgender men and cisgender women. Transgender men survivors were significantly more likely to report poor physical health and greater medical comorbidities and were less likely to report smoking compared with cisgender men and cisgender women. Transgender women survivors were significantly more likely to report diabetes compared with cisgender men and cisgender women and were more likely to report cardiovascular disease compared with cisgender women. CONCLUSIONS: Clinicians should be aware of the higher prevalence of cancer among transgender men and a potential survivorship bias among transgender individuals. Transgender survivors have considerable variation in their risk profile. Clinicians and health services can target gender nonconforming survivors' depression and health behaviors to improve survival and should address the complex comorbidities of transgender men and transgender women.

Cyclic AMP in human preterm infant blood is associated with increased TLR-mediated production of acute-phase and anti-inflammatory cytokines in vitro.

BACKGROUND: Preterm infants are at high risk of infection and have distinct pathogen recognition responses. Suggested mechanisms include soluble mediators that enhance cellular levels of cAMP. The aim of this study was to assess the relationship between blood cAMP concentrations and TLR-mediated cytokine production in infants during the first month of life. METHODS: Cord and serial peripheral blood samples (days of life 1-28) were obtained from a cohort of very preterm (<30 weeks' gestational age) and term human infants. Whole-blood concentrations of cAMP and FSL-1 and LPS in vitro stimulated cytokine concentrations were measured by ELISA and multiplex bead assay. RESULTS: cAMP concentrations were higher in cord than in peripheral blood, higher in cord blood of female preterm infants, and lower at Days 1 and 7 in infants exposed to chorioamnionitis, even after adjusting for leukocyte counts. TLR2 and TLR4-mediated TNF-α, IL-1ß, IL-6, IL-12p70, and IL-10 production in vitro increased over the first month of life in preterm infants and were positively correlated with leukocyte-adjusted cAMP levels and reduced by exposure to chorioamnionitis. CONCLUSIONS: The ontogeny of blood cAMP concentrations and associations with chorioamnionitis and TLR-mediated production of cytokines suggest that this secondary messenger helps shape distinct neonatal pathogen responses in early life.

COVID-19 Misinformation Spread in Eight Countries: Exponential Growth Modeling Study.

BACKGROUND: The epidemic of misinformation about COVID-19 transmission, prevention, and treatment has been going on since the start of the pandemic. However, data on the exposure and impact of misinformation is not readily available. OBJECTIVE: We aim to characterize and compare the start, peak, and doubling time of COVID-19 misinformation topics across 8 countries using an exponential growth model usually employed to study infectious disease epidemics. METHODS: COVID-19 misinformation topics were selected from the World Health Organization Mythbusters website. Data representing exposure was obtained from the Google Trends application programming interface for 8 English-speaking countries. Exponential growth models were used in modeling trends for each country. RESULTS: Searches for "coronavirus AND 5G" started at different times but peaked in the same week for 6 countries. Searches for 5G also had the shortest doubling time across all misinformation topics, with the shortest time in Nigeria and South Africa (approximately 4-5 days). Searches for "coronavirus AND ginger" started at the same time (the week of January 19, 2020) for several countries, but peaks were incongruent, and searches did not always grow exponentially after the initial week. Searches for "coronavirus AND sun" had different start times across countries but peaked at the same time for multiple countries. CONCLUSIONS: Patterns in the start, peak, and doubling time for "coronavirus AND 5G" were different from the other misinformation topics and were mostly consistent across countries assessed, which might be attributable to a lack of public understanding of 5G technology. Understanding the spread of misinformation, similarities and differences across different contexts can help in the development of appropriate interventions for limiting its impact similar to how we address infectious disease epidemics. Furthermore, the rapid proliferation of misinformation that discourages adherence to public health interventions could be predictive of future increases in disease cases.

Cancer survivors' access to care and quality of life: Do sexual minorities fare worse than heterosexuals?

BACKGROUND: Adults with poor access to care are known to have worse quality of life (QOL). The purpose of the current study was to determine differences in cancer survivors' access to care by sexual orientation and to examine the association between access to care and QOL. METHODS: The current secondary data analysis used 4 years of Behavioral Risk Factor Surveillance System data regarding adult men and women who self-reported a history of cancer. Among the 70,524 cancer survivors, a total of 1931 self-identified as sexual minorities, defined as lesbian, gay, bisexual, or other nonheterosexual orientation. RESULTS: Sexual minority women had significantly more access deficits compared with heterosexual women (42.7% vs 28.0%; P < .0001), whereas men of different sexual orientations had similar access to care. Among sexual minority women, those with access deficits had higher odds of poor physical QOL compared with heterosexual women (odds ratio [OR], 2.0 [95% CI, 1.2-3.4] vs OR, 1.3 [95% CI, 1.2-1.5]), poor mental QOL (OR, 1.8 [95% CI, 1.1-3.1] vs OR, 1.5 [95% CI, 1.3-1.7]), and difficulties concentrating (OR, 2.0 [95% CI, 1.2-3.5] vs OR, 1.7 [95% CI, 1.4-1.9]). Sexual minority men with access deficits had greater odds of difficulty concentrating compared with heterosexual men (OR, 4.3 [95% CI, 2.0-9.3] vs OR, 1.5 [95% CI, 1.2-1.9]). Among men, sexual minority status increased the odds of poor mental QOL (OR, 1.49 [95% CI, 1.11-2.01]). CONCLUSIONS: Access to care among sexual minority cancer survivors needs improvement. Sexual minority women should be a focus of future research because their poor access to care more strongly relates to worse QOL.