Factors Associated With Anal High-Grade Intraepithelial Lesions and Carcinoma Among Young Men Who Have Sex With Men and Transgender Women With HIV in Atlanta.

OBJECTIVE: This study aimed to evaluate factors associated with anal high-grade intraepithelial lesions (HSIL) and anal carcinoma among young men who have sex with men (MSM) and transgender women (TW) with HIV in Atlanta, GA, to better inform screening guidelines and preventative measures. MATERIALS AND METHODS: Cross-sectional retrospective chart review was completed for cisgender MSM and TW with HIV aged 13-25 years at the Grady Ponce and Family Youth Clinic in Atlanta, GA, from 2009 to 2020. High-grade anal disease was defined as anal intraepithelial neoplasia (AIN) 2, 3, or anal carcinoma (AIN 2+). Associations between clinical and demographic factors with AIN 2+ were estimated using logistic regression. Adjusted odds ratios (aORs) and associated 90% CIs are reported. RESULTS: One hundred nine MSM and TW with HIV who underwent anoscopy were included. One hundred three participants received anal biopsies, and 62% had AIN 2+. Being incompletely or unvaccinated against human papillomavirus (HPV, 0-2 doses) relative to being fully vaccinated (3 doses; aOR = 5.85; 90% CI = 1.28-26.83; p = .06) and having ever received surgical treatment for anogenital HPV (aOR = 2.89; 90% CI = 1.10-7.65; p = .07) were associated with AIN 2+, controlling for age and CD4 T-cell count at time of biopsy. CONCLUSIONS: Our study found a high prevalence of anal HSIL among young MSM and TW with HIV. Those who had ever received surgical treatment for anogenital HPV and those who were incompletely or unvaccinated against HPV were more likely to have HSIL. Our data emphasize the urgent need to improve HPV vaccination efforts and to pursue larger surveillance studies of anal HSIL and carcinoma among young MSM and TW with HIV.

Structural basis for nonneutralizing antibody competition at antigenic site II of the respiratory syncytial virus fusion protein.

Palivizumab was the first antiviral monoclonal antibody (mAb) approved for therapeutic use in humans, and remains a prophylactic treatment for infants at risk for severe disease because of respiratory syncytial virus (RSV). Palivizumab is an engineered humanized version of a murine mAb targeting antigenic site II of the RSV fusion (F) protein, a key target in vaccine development. There are limited reported naturally occurring human mAbs to site II; therefore, the structural basis for human antibody recognition of this major antigenic site is poorly understood. Here, we describe a nonneutralizing class of site II-specific mAbs that competed for binding with palivizumab to postfusion RSV F protein. We also describe two classes of site II-specific neutralizing mAbs, one of which escaped competition with nonneutralizing mAbs. An X-ray crystal structure of the neutralizing mAb 14N4 in complex with F protein showed that the binding angle at which human neutralizing mAbs interact with antigenic site II determines whether or not nonneutralizing antibodies compete with their binding. Fine-mapping studies determined that nonneutralizing mAbs that interfere with binding of neutralizing mAbs recognize site II with a pose that facilitates binding to an epitope containing F surface residues on a neighboring protomer. Neutralizing antibodies, like motavizumab and a new mAb designated 3J20 that escape interference by the inhibiting mAbs, avoid such contact by binding at an angle that is shifted away from the nonneutralizing site. Furthermore, binding to rationally and computationally designed site II helix-loop-helix epitope-scaffold vaccines distinguished neutralizing from nonneutralizing site II antibodies.

Incidence of Sexually Transmitted Infections in Youth with HIV During Pre-COVID and COVID Era.

Adolescents and young adults (AYAs) living with HIV have high rates of co-sexually transmitted infections (STIs). During the coronavirus disease (COVID) pandemic, STI prevention strategies, including access to testing/treatment facilities, availability of health care workers, and condom availability, may have decreased. This study aimed to determine if differences in STI incidence for first infection and reinfection existed between the pre-COVID and COVID eras in a cohort of AYAs living with HIV in Atlanta, GA. Retrospective chart review was conducted for all patients between ages 13 and 24 at the Grady Ponce Clinic. Two eras were identified: a pre-COVID era (January 1, 2009-December31, 2019) and a COVID era (January 1, 2020-June 30, 2021). STIs recorded included gonorrhea, chlamydia, human papillomavirus, syphilis, trichomonas, herpes simplex virus, lymphogranuloma venereum, hepatitis C, bacterial vaginosis, and chancroid. First and recurrent incidence rates for any STIs were reported. Our sample included 766 sexually active AYAs with HIV. A total of 721 patients were included in the pre-COVID era and 583 (80.9%) had at least one STI. A total of 337 patients were included in the COVID era, and 158 had at least one STI (46.9%). The overall first STI incidence rate increased from 42.47 to 58.67 per 100 person-years (PY) and the recurrent STI incidence rate increased from 121.50 to 169.85 per 100 PY from the pre-COVID to the COVID era (p < 0.001). Our study demonstrated significantly higher incidence rates of first and recurrent STIs in AYAs living with HIV in the COVID era. We urge continuation of existing STI prevention programs to avoid secondary clinical and economic adverse effects of increased infections.

Reactive Case Detection and Treatment and Reactive Drug Administration for Reducing Malaria Transmission: A Systematic Review and Meta-Analysis.

Many countries pursuing malaria elimination implement "reactive" strategies targeting household members and neighbors of index cases to reduce transmission. These strategies include reactive case detection and treatment (RACDT; testing and treating those positive) and reactive drug administration (RDA; providing antimalarials without testing). We conducted systematic reviews of RACDT and RDA to assess their effect on reducing malaria transmission and gathered evidence about key contextual factors important to their implementation. Two reviewers screened titles/abstracts and full-text records using defined criteria (Patient = those in malaria-endemic/receptive areas; Intervention = RACDT or RDA; Comparison = standard of care; Outcome = malaria incidence/prevalence) and abstracted data for meta-analyses. The Grading of Recommendations, Assessment, Development, and Evaluations approach was used to rate certainty of evidence (CoE) for each outcome. Of 1,460 records screened, reviewers identified five RACDT studies (three cluster-randomized controlled trials [cRCTs] and two nonrandomized studies [NRS]) and seven RDA studies (six cRCTs and one NRS); three cRCTs comparing RDA to RACDT were included in both reviews. Compared with RDA, RACDT was associated with nonsignificantly higher parasite prevalence (odds ratio [OR] = 1.85; 95% CI: 0.96-3.57; one study) and malaria incidence (rate ratio [RR] = 1.30; 95% CI: 0.94-1.79; three studies), both very low CoE. Compared with control or RACDT, RDA was associated with non-significantly lower parasite incidence (RR = 0.73; 95% CI: 0.36-1.47; 2 studies, moderate CoE), prevalence (OR = 0.78; 95% CI: 0.52-1.17; 4 studies, low CoE), and malaria incidence (RR = 0.93; 95% CI: 0.82-1.05; six studies, moderate CoE). Evidence for reactive strategies' impact on malaria transmission is limited, especially for RACDT, but suggests RDA might be more effective.

Sleep Characteristics in Pediatric Anti-N-methyl-d-aspartate (NMDA) Receptor Encephalitis: A Retrospective Cohort Study.

Background: Rates of sleep problems in children with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis are unknown. Methods: We used a retrospective observational cohort database of children with a diagnosis of NMDA receptor encephalitis at a single freestanding institution. One-year outcomes were assessed with the pediatric modified Rankin Score (mRS), with 0 to 2 as good and 3 or greater as poor outcome. Results: Ninety-five percent (39/41) of children with NMDA receptor encephalitis had sleep dysfunction at onset; 34% (11/32) reported sleep problems at 1 year. Sleep problems at onset and propofol use were not associated with poor outcomes at 1 year. Poor sleep at 1 year correlated with mRS scores (range 2-5) at 1 year. Discussion: High rates of sleep dysfunction occur in children with NMDA receptor encephalitis. Persistent sleep problems at 1 year may correlate with outcomes as assessed by mRS at 1 year. Further studies comparing the relationship of poor sleep with outcomes in NMDA receptor encephalitis are needed.

The neutrophil-to-lymphocyte ratio is associated with intubation in pediatric anti-NMDA receptor encephalitis: A retrospective study.

Background The neutrophil-to-lymphocyte ratio (NLR) may predict poor outcomes in adult anti-NMDAR encephalitis (NMDARE). The association of NLR with outcomes in pediatric NMDARE was examined. Methods Pediatric NMDARE patients (N = 36) were retrospectively studied. Results High NLR (>6) had a higher proportion of tumors (43% versus 7%) and higher intubation rates (100% versus 38%, p = 0.008). Multivariate analyses showed that high NLR did not correlate with one-year outcomes, inpatient length of stay (LOS), or with tumor, but was associated with intubation and rehabilitation LOS. Conclusion NLR is associated with intubation and rehabilitation LOS. Further investigation is needed for prognostic biomarkers in NMDARE.

Incidence, Reinfection, and Discrepancy Between Sexual Practice and Anatomic Site Positivity of Sexually Transmitted Infections in Youth With HIV.

BACKGROUND: This study aimed to determine the overall incidence and reinfection rates of sexually transmitted infections (STIs) and the discrepancy between self-reported exposure history and anatomic site positivity of STIs among adolescents and young adults (AYAs) with HIV in Atlanta, GA. METHODS: Retrospective chart review was conducted on all patients 13-24 years of age at the Grady Ponce and Family Youth Clinic from January 1, 2009 to December 31, 2018. Data were collected on patient demographics, self-reported sexual history and STI events. First STI incidence and incidence of reinfections were calculated by dividing new cases over corresponding person follow-up time. RESULTS: A total of 626 sexually active AYAs with HIV were included in analysis. The mean age at first observation was 18.9 (SD: ±2.8) years; 72% were male, 92% were Black and 80% were horizontally infected. The cumulative first STI incidence rate was 45.49 cases per 100 person-years, and the recurrent STI incidence rate was 119.86 cases per 100 person-years. Among all Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) cases, the most common site of infection was the rectum (48.6% and 49.6%, respectively). Disagreement between exposure history and presence of GC or CT infection was statistically significant for nearly all anatomic sites and types of intercourse. CONCLUSIONS: AYAs with HIV in Atlanta have disproportionately high first and recurrent incidence rates of STIs, with many patients not reporting exposure at their site of infection. There is considerable need to increase screening for STIs, including routine extragenital testing for GC and CT, among AYAs with HIV regardless of self-reported exposure history.

Electroencephalography characteristics to predict one-year outcomes in pediatric anti-NMDA receptor encephalitis.

BACKGROUND: Electrographic characteristics (extreme delta brush, posterior dominant rhythm and slow waves) may predict outcomes in anti-NMDA receptor encephalitis (NMDARE). However, whether changes in EEG sleep architecture predict outcomes are unknown. We examine electrophysiological characteristics including sleep architecture in a pediatric NMDARE population and correlate with outcomes at one year. METHODS: Retrospective chart and EEG review was performed in pediatric NMDARE patients at a single center. Patients with first EEGs available within 48 h of admission, prior to treatment, and one-year follow-up data were included. EEGs were independently reviewed by two epileptologists, and a third when disagreement occurred. Clinical outcomes included modified Rankin scale (mRS) at one year. RESULTS: Nine patients (6 females) (range 1.9-16.7 years) were included. Five of nine patients had loss of posterior dominant rhythm (PDR) and three of nine patients had absent sleep architecture. Loss of PDR correlated with a worse mRS score at one year (2.8 versus 0.5, p = 0.038). Loss of PDR and loss of sleep architecture was associated with increased inpatient rehabilitation stay and in higher number of immunotherapy treatments administered. In multivariate analysis, absence of sleep architecture (p = 0.028), absence of PDR (p = 0.041), and epileptiform discharges (p = 0.041) were predictors of mRS at one year. CONCLUSIONS: Loss of normal PDR, absence of sleep architecture, and epileptiform discharges are associated with worse outcomes at one year which has not been reported before. EEG characteristics may help prognosticate in NMDARE. Larger studies are needed to confirm these findings.

Discharge characteristics and care transitions of hospitalized patients with COVID-19.

Little is known about the follow-up healthcare needs of patients hospitalized with coronavirus disease 2019 (COVID-19) after hospital discharge. Due to the unique circumstances of providing transitional care in a pandemic, post-discharge providers must adapt to specific needs and limitations identified for the care of COVID-19 patients. In this study, we conducted a retrospective chart review of all hospitalized COVID-19 patients discharged from an Emory Healthcare Hospital in Atlanta, GA from March 26 to April 21, 2020 to characterize their post-discharge care plans. A total of 310 patients were included in the study (median age 58, range: 23-99; 51.0% female; 69.0% African American). The most common presenting comorbidities were hypertension (200, 64.5%), obesity (BMI≥30) (138, 44.5%), and diabetes mellitus (112, 36.1%). The median length of hospitalization was 5 days (range: 0-33). Sixty-seven patients (21.6%) were admitted to the intensive care unit and 42 patients (13.5%) received invasive mechanical ventilation. The most common complications recorded at discharge were electrolyte abnormalities (124, 40.0%), acute kidney injury (86, 27.7%) and sepsis (55, 17.7%). The majority of patients were discharged directly home (281, 90.6%). Seventy-five patients (24.2%) required any home service including home health and home oxygen therapy. The most common follow-up need was an appointment with a primary care provider (258, 83.2%). Twenty-four patients (7.7%) had one or more visit to an ED after discharge and 16 patients (5.2%) were readmitted. To our knowledge, this is the first large study to report on post-discharge medical care for COVID-19 patients.

Characteristics and outcomes of COVID-19 positive patients with diabetes managed as outpatients.

We analyzed disease outcomes for patients with diabetes and laboratory-confirmed COVID-19 who were managed outpatient and followed by the Emory COVID-19 Virtual Outpatient Management Clinic (ECVOMC). The rate of hospitalization for patients with diabetes was double the overall rate of hospitalization for patients in the ECVOMC.

Broadly neutralizing antibodies with few somatic mutations and hepatitis C virus clearance.

Here, we report the isolation of broadly neutralizing mAbs (bNAbs) from persons with broadly neutralizing serum who spontaneously cleared hepatitis C virus (HCV) infection. We found that bNAbs from two donors bound the same epitope and were encoded by the same germline heavy chain variable gene segment. Remarkably, these bNAbs were encoded by antibody variable genes with sparse somatic mutations. For one of the most potent bNAbs, these somatic mutations were critical for antibody neutralizing breadth and for binding to autologous envelope variants circulating late in infection. However, somatic mutations were not necessary for binding of the bNAb unmutated ancestor to envelope proteins of early autologous transmitted/founder viruses. This study identifies a public B cell clonotype favoring early recognition of a conserved HCV epitope, proving that anti-HCV bNAbs can achieve substantial neutralizing breadth with relatively few somatic mutations, and identifies HCV envelope variants that favored selection and maturation of an anti-HCV bNAb in vivo. These data provide insight into the molecular mechanisms of immune-mediated clearance of HCV infection and present a roadmap to guide development of a vaccine capable of stimulating anti-HCV bNAbs with a physiologic number of somatic mutations characteristic of vaccine responses.