Acknowledgment of Ad Hoc Reviewers for Volume 13

Note

Acknowledgment of Ad Hoc Reviewers for Volume 13     

Prevalence, Risk Factors, and Accuracy of Cytologic Screening for Cervical Intraepithelial Neoplasia in Women with the Human Immunodeficiency Virus

Objectives.The objective was to evaluate the sensitivity and specificity of cervical cytology in women infected with the human immunodeficiency virus (HIV), risk factors for abnormal cytology in HIV-infected and uninfected women, and risk factors for histologic diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-infected women.Methods.Methods included a cross-sectional analysis of cervical cytology, colposcopic impression, and histology in 248 HIV-infected women and multivariate analyses of risk factors for abnormal cytology in 253 HIV-infected and 220 uninfected women and risk factors for CIN in 186 HIV-infected women.Results.The sensitivity and specificity of cytology for all CIN grades were 0.60 and 0.80 and, for high-grade CIN, 0.83 and 0.74. The prevalence of abnormal cytology was 32.9% in HIV-infected and 7.6% in HIV-negative women. Independent risk factors for abnormal cytology were immunodeficiency [odds ratio (OR) 8–17,P< 0.001] and human papillomavirus (HPV) infection (OR = 5,P< 0.001). The prevalence of CIN on histology was 32% in HIV-infected women, and the only independent risk factor for CIN was oncogenic HPV type (OR = 5,P= 0.005).Conclusion.Given the high prevalence of abnormal cytology and CIN in HIV-infected women, cytologic screening has significant limitations. Both immunodeficiency and type of HPV infection are important risk factors.     

Multimorbidity and healthcare utilization among early survivors of pediatric cancer

Early survivors of pediatric cancer are at increased risk of experiencing chronic conditions; however, little is known about the morbidity burden in this population. In this observational cohort study of commercially insured pediatric cancer survivors in the United States (2009–2014), we find that 22.5% of survivors had one chronic condition, and 36.3% had multiple. Compared with survivors without chronic conditions, the presence of multiple conditions significantly increased the odds of an emergency department visit by 70% (odds ratios [OR], 1.7; 95% confidence interval [CI], 1.4–2.1) and of a hospitalization almost four‐fold (OR, 3.8; 95% CI], 2.5–5.5). Findings are important for informing pediatric survivorship care plans in the years following completion of therapy.     

Cortical Atrophy Predicts Visual Performance in Long-Term Central Retinal Disease; GCL,pRNFL and Cortical Thickness Are Key Biomarkers

PurposeThe aim of this study was to assess both retinal and cortical structure in a cohort of patients with long-term acquired central retinal disease in order to identify potential disease biomarkers and to explore the relationship between the anterior and posterior visual pathways.MethodsFourteen participants diagnosed with long-term central retinal disease underwent structural assessments of the retina using spectral-domain optical coherence tomography, including macular ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness. Structural magnetic resonance imaging was used to measure visual cortex, including cortical volume of the entire occipital lobe and cortical thickness of the occipital pole and calcarine sulcus, representing the central and peripheral retina, respectively.ResultsMean thickness was significantly reduced in both the macular GCL and the inferior temporal pRNFL across patients. Cortical thickness was significantly reduced in both the occipital pole and calcarine sulcus, representing the central and peripheral retina, respectively. Disease duration significantly correlated with GCL thickness with a large effect size, whereas a medium effect size suggests the possibility that cortical thickness in the occipital pole may correlate with visual acuity.ConclusionsLong-term central retinal disease is associated with significant structural changes to both the retina and the brain. Exploratory analysis suggests that monitoring GCL thickness may be a sensitive biomarker of disease progression and reductions in visual cortical thickness may be associated with reduced visual acuity. Although this study is limited by its heterogeneous population, larger cohort studies would be needed to better establish some of the relationships detected between disease dependent structural properties of the anterior and posterior visual pathway given the effect sizes reported in our exploratory analysis.     

An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer

The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope (“supersite”) on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRA-Seq), we isolated a large panel of NTD-reactive and SARS-CoV-2–neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, forming a genetic cluster representing a public B cell clonotype. However, we also discovered a rare human antibody, COV2-3434, that recognizes a site of vulnerability on the SARS-CoV-2 S protein in the trimer interface (TI) and possesses a distinct class of functional activity. COV2-3434 disrupted the integrity of S protein trimers, inhibited the cell-to-cell spread of the virus in culture, and conferred protection in human angiotensin-converting enzyme 2–transgenic (ACE2-transgenic) mice against the SARS-CoV-2 challenge. This study provides insight into antibody targeting of the S protein TI region, suggesting this region may be a site of virus vulnerability.     

Virome of Ixodes ricinus,Dermacentor reticulatus,and Haemaphysalis concinna Ticks from Croatia

Tick-borne diseases are a serious threat to both public and veterinary health. In this study, we used high-throughput sequencing to characterize the virome of three tick species implicated in the spread of vector-borne disease throughout Croatia. Ten viruses were identified, including seven potential novel species within the viral families Flaviviridae, Nyamiviridae, Rhabdoviridae, Peribunyaviridae, Phenuiviridae, and Nairoviridae.     

How we make choices and sacrifices in medical education during the COVID-19 pandemic

Abstract

In this commentary, we highlight some of the pressing choices and sacrifices we must make in medical education during the COVID-19 pandemic.     

Clinical Outcomes and Resource Use for Infants With Hypoplastic Left Heart Syndrome During Bidirectional Glenn: Summary From the Joint Council for Congenital Heart Disease National Pediatric Cardiology Quality Improvement Collaborative Registry

The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) registry captures information on interstage management of infants with hypoplastic left heart syndrome (HLHS). The purpose of this study was to identify interstage risk factors for increased resource use and adverse outcomes during bidirectional Glenn (BDG) hospitalization. All infants in the NPC-QIC registry (31 United States hospitals) undergoing BDG surgery were included (December 2009 to August 2010). Patient demographics, interstage variables, operative procedures, and complications were recorded. Days of hospitalization, ventilation, inotrope use, and complications were surrogates of resource use. Logistic regression analysis determined the associations between predictor variables and resource use. Of 162 infants, 105 (65 %) were males. At BDG, the median age was 155 days (range 78–128), mean weight-for-age z-score was ?1.6 ± 1.1, mean length-for-age z-score was ?1.5 ± 1.7, and mean preoperative oxygen saturation was 78 % ± 7 %. Caloric recommendations were met in 60 % of patients, and 85 % of patients participated in a home-surveillance program. Median days of intubation, inotrope use, and hospitalization were 1, 2, and 7, respectively. There were 4 post-BDG deaths and 55 complications. In multivariate analysis, lower weight-for-age z-score, female sex, and aortic atresia with mitral stenosis were associated with a higher risk of BDG complications. Meeting caloric recommendations before BDG was associated with fewer hospitalization days. Lower weight-for-age z-score was an independent and potentially modifiable risk factor for BDG complications. HLHS infants who met caloric recommendations before BDG had a lower duration of hospitalization at BDG. These data justify targeting nutrition in interstage strategies to improve outcomes and decrease costs for patients with HLHS.