Variable Performance in 6 Commercial SARS-CoV-2 Antibody Assays May Affect Convalescent Plasma and Seroprevalence Screening.

OBJECTIVES: Serologic detection of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is needed for definition of convalescent plasma donors, for confounding SARS-CoV-2 presentation, and for seroprevalence studies. Reliable serologic assays with independent validation are required. METHODS: Six SARS-CoV-2 antibody assays from Beckman Coulter, Euroimmun (IgG, IgA), Roche, and Siemens (Centaur, Vista) were assessed for specificity (n = 184), sensitivity (n = 154), and seroconversion in a defined cohort with clinical correlates and molecular SARS-CoV-2 results. RESULTS: Assay specificity was 99% or greater for all assays except the Euroimmun IgA (95%). Sensitivity at more than 21 days from symptom onset was 84%, 95%, 72%, 98%, 67%, and 96% for Beckman Coulter, Centaur, Vista, Roche, Euroimmun IgA, and Euroimmun IgG, respectively. Average day of seroconversion was similar between assays (8-10 d), with 2 patients not producing nucleocapsid antibodies during hospitalization. CONCLUSIONS: SARS-CoV-2 nucleocapsid antibodies may be less reliably produced early in disease than spike protein antibodies. Assessment of convalescent plasma donors at more than 30 days from symptom onset and seroprevalence studies should use assays with defined sensitivity at time points of interest because not all assays detected antibodies reliably at more than 30 days.

Herpes Simplex Virus-1 qPCR in the Diagnosis of Lower Respiratory Tract Infections in Organ Transplant Recipients and Critically Ill Patients.

OBJECTIVES: To determine a quantitative herpes simplex virus (HSV) DNA threshold in lower respiratory tract specimens that correlates with positive viral culture and clinical outcomes. METHODS: Bronchoalveolar lavage and bronchial wash samples from 53 HSV culture-positive and 61 culture-negative matched controls were tested using HSV-1 and HSV-2 quantitative polymerase chain reaction (qPCR). RESULTS: Median viral culture turnaround time was 21.8 days and 9.9 days for culture-negative and culture-positive specimens, respectively. Using an HSV-1 viral load threshold of 1.62 × 103 copies/mL, there was 93% agreement with viral culture. An HSV-1 viral load ≥1.3 × 104 copies/mL was associated with worse clinical outcome compared to a viral load <1.3 × 104 copies/mL (hazard ratio [HR] = 4.27, P = .017), and there was a trend of worse outcome compared to patients with undetectable HSV-1 DNA (HR = 1.60, P = .056). CONCLUSIONS: qPCR has clinical utility for rapid accurate identification of HSV-1 in lower respiratory tract specimens.

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease.

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management.

Liver protects metastatic prostate cancer from induced death by activating E-cadherin signaling.

Liver is one of the most common sites of cancer metastasis. Once disseminated, the prognosis is poor as these tumors often display generalized chemoresistance, particularly for carcinomas that derive not from the aerodigestive tract. When these cancers seed the liver, the aggressive cells usually undergo a mesenchymal to epithelial reverting transition that both aids colonization and renders the tumor cells chemoresistant. In vitro studies demonstrate that hepatocytes drive this phenotypic shift. However, the in vivo evidence and the molecular signals that protect these cells from induced death are yet to be defined. Herein, we report that membrane surface E-cadherin-expressing prostate cancer cells were resistant to cell death by chemotherapeutic drugs but E-cadherin null cells or those expressing E-cadherin only in the cytoplasm were sensitive to death signals and chemotherapies both in vitro and in vivo. While cell-cell E-cadherin ligandation reduced mitogenesis, this chemoprotection was proliferation-independent as killing of both 5-ethynyl-2'-deoxyuridine-positive (or Ki67+ ) and 5-ethynyl-2'-deoxyuridine-negative (Ki67- ) cells was inversely related to membrane-bound E-cadherin. Inhibiting the canonical survival kinases extracellular signal-regulated protein kinases, protein kinase B, and Janus kinase, which are activated by chemotherapeutics in epithelial cell-transitioned prostate cancer, abrogated the chemoresistance both in cell culture and in animal models of metastatic cancer. For disseminated tumors, protein kinase B disruption in itself had no effect on tumor survival but was synergistic with chemotherapy, leading to increased killing. CONCLUSION: Liver microenvironment-driven phenotypic switching of carcinoma cells and subsequent survival signaling results in activation of canonical survival pathways that protect the disseminated prostate cancer liver micrometastases in a proliferation-independent manner, and these pathways can be targeted as an adjuvant treatment to improve the efficacy of traditional chemotherapeutics (Hepatology 2016;64:1725-1742).

Uso de lâminas de 0, 7 a 1 mm de largura e incisões coronais no transplante capilar: Táticas cirúrgica para melhorar a densidade e naturalidade / Use of blades of 0.7 to 1 mm in diameter and coronal incisions in hair transplantation: Surgical approach to improve density and natural results

The hair transplant evolved greatly in the past two decades primarily by the use of microscopes to make follicular units. The use of Micro blades is another step to reduce the surgical trauma and increase the naturalness of the result. Coronal incisions help to maintain the correct directionof hair placed. The goal of this work is to show our experience with the use of blades 0.7 to 1 mm in diameter, with coronal incisions for hair transplantatiQn. Method: We evaluated 131 consecutive surgeries from June 2011 to June 2012, in which all patients operated on by the some surgeon with the use of microblades 0.7 to 1 mm wide using coronal incisions. Results: The postoperative results were considered satisfacfory by the patients and the surgical team. Conclusion: The use of small blades with coronal incisions helps to give more density with little surgical trauma. The results were considered natural with good cosmetic density...

O transplante capilar evoluiu muito nas últimas duas décadas, principalmente com o uso de microscópios para lapidar unidades foliculares. A utilização de microlâminas é mais um avanço para diminuir o trauma cirúrgico e aumentar a naturalidade do resultado. As incisões coronais ajudam a manter a direção correta dos cabelos colocados. O objetivo deste trabalho é mostrar nossa experiência com o uso de lâminas de 0.7 a 1 mm de diâmetro, com incisões coronais para o transplante capilar. Método: Foram avaliadas 131 cirurgias consecutivas de junho de 2011 a junho de 2012, em que todos os pacientes foram operados pelo mesmo cirurgião, com o uso de microlâminas de 0.7 a 1 mm de largura utilizando a técnica coronal para a incisão. Resultados: Os resultados pós-operatórios foram considerados satisfatórios pelos pacientes e pela equipe cirúrgica. Conclusão: O uso de lâminas pequenas nas incisões coronárias promove maior densidade com pouco trauma cirúrgico. Os resultados foram considerados naturais com boa densidade cosmética...