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.     

Shoulder dystocia: a comparison of patients with and without diabetes mellitus

Background: The study was aimed to compare pregnancies complicated with shoulder dystocia, of patients with and without diabetes mellitus. Methods: A comparison of all singleton, vertex, term deliveries between the years 1988–1999, complicated with shoulder dystocia with and without diabetes mellitus was performed. Statistical analysis was done using receiver operating characteristic curve analysis. Results: Using a receiver operating characteristic curve analysis, the area under the curve for birth weight was 0.92 (95% CI 0.90–0.93). However, for birth weight of 4,000 g the sensitivity was only 56% with specificity of 95%. While comparing shoulder dystocia between patients with (n=38) and without diabetes mellitus (n=207), neonates of the diabetic patients were significantly heavier (mean birth weight 4,244.2±515.1 vs. 4,051.6±389.5; P=0.008) and had higher rate of Apgar scores lower than 7 at 1 min (50.0% vs. 25.9%; P=0.030), but not at 5 min (2.6% vs. 2.0%; P=0.083) when compared to the non-diabetic group. No significant differences were noted regarding perinatal mortality between the groups (0% vs. 4.3%; P=0.362). Conclusions: The newborn of the diabetic mother complicated with shoulder dystocia does not appear to be at an increased risk for perinatal morbidity compared with the newborn of the non-diabetic mother. Presented in part at the Society for Gynecologic Investigation 50th Annual Scientific Meeting, Washington, DC, 27–30 March 2003.     

Complications of combined radical hysterectomy and pelvic radiation

Long-term gastrointestinal (GI) and urinary tract (UT) complications were evaluated in 48 women treated by radical hysterectomy (RH) and pelvic node dissection (PND) and in 25 women who received 5000–5400 rad of external pelvic radiation (RT) after RH-PND. No major complications developed in the surgery-only group, but the 5-year minor GI complication rate was 4% and the 5-year minor UT complication rate was 10%. In 9 patients receiving RT at 200 rad/day, one major GI complication (13%) and one major UT complication (14%) developed. In 16 patients receiving RT at 180 rad/day only minor GI complications (7%) and minor UT complications (13%) developed. The conclusion is that after RH-PND, adjunctive RT delivered at 180 rad/day through four ports results in acceptable, minimal complications.     

dPQL: a lossless distributed algorithm for generalized linear mixed model with application to privacy-preserving hospital profiling

ObjectiveTo develop a lossless distributed algorithm for generalized linear mixed model (GLMM) with application to privacy-preserving hospital profiling.Materials and MethodsThe GLMM is often fitted to implement hospital profiling, using clinical or administrative claims data. Due to individual patient data (IPD) privacy regulations and the computational complexity of GLMM, a distributed algorithm for hospital profiling is needed. We develop a novel distributed penalized quasi-likelihood (dPQL) algorithm to fit GLMM when only aggregated data, rather than IPD, can be shared across hospitals. We also show that the standardized mortality rates, which are often reported as the results of hospital profiling, can also be calculated distributively without sharing IPD. We demonstrate the applicability of the proposed dPQL algorithm by ranking 929 hospitals for coronavirus disease 2019 (COVID-19) mortality or referral to hospice that have been previously studied.ResultsThe proposed dPQL algorithm is mathematically proven to be lossless, that is, it obtains identical results as if IPD were pooled from all hospitals. In the example of hospital profiling regarding COVID-19 mortality, the dPQL algorithm reached convergence with only 5 iterations, and the estimation of fixed effects, random effects, and mortality rates were identical to that of the PQL from pooled data.ConclusionThe dPQL algorithm is lossless, privacy-preserving and fast-converging for fitting GLMM. It provides an extremely suitable and convenient distributed approach for hospital profiling.     

A Phase I/II study of docetaxel, etoposide, and carboplatin before concurrent chemoradiotherapy with cisplatin and etoposide in limited-stage small cell lung cancer

Summary Limited stage small cell lung cancer (LS-SCLC) is an infrequent but aggressive tumor. No major advances in the treatment of this disease have been achieved in recent years. This study was conducted to determine the maximum-tolerated dose (MTD) and efficacy of docetaxel, etoposide, and carboplatin (DEC) given before definitive chest radiotherapy with concurrent cisplatin and etoposide. Seventeen untreated LS-SCLC patients received docetaxel 50 mg/m², etoposide 50–80 mg/m², and carboplatin AUC = 5–6, intravenously on day 1 followed by etoposide 100–160 mg/m² orally on days 2 and 3 every 21 days for two cycles followed by once daily radiotherapy to a total dose of 50 Gy given concurrently with cisplatin (60 mg/m², d1) and etoposide (120 mg/m², d1 and 240 mg/m² day 2–3) for 2 cycles. All patients were assessable for toxicity and 15 for response. The most frequent toxicity was grade 3 and 4 neutropenia in 41% of patients during DEC and in 57% with chemoradiation. The MTD for DEC was docetaxel 50 mg/m² plus carboplatin AUC = 5 and etoposide 50/100 mg/m² with growth factor support. Significant nonhematologic toxicities were primarily radiation-related esophagitis (43%). One patient (6%) died from toxicity. The overall response rate was 82% with 10 patients (59%) achieving a complete response. The median survival was 12.1 months (95% CI, 6.4–17.8 months) and the 1-year survival rate was 47%. This novel approach produced similar efficacy results to current two drug regimens but was associated with significant neutropenia. Alternative strategies to increase complete response rates and survival are needed.