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To assess the feasibility of fetoscopy-guided bipolar umbilical cord coagulation for selective fetal reduction in complicated monochorionic diamniotic (MCDA) twin pregnancies.MCDA twins undergoing fetoscopy-guided bipolar cord coagulation (BCC) were enrolled prospectively between December 2015 to March 2020 in a fetal medicine center.Twenty-three cases undergoing fetoscopy-guided BCC were finally analyzed, including 11 cases for type 2 selective intrauterine growth restriction, 4 cases for twin-twin transfusion syndrome, and 8 cases for a severe discordant anomaly. The overall survival rate was 78.3% (18/23).Fetoscopy-guided BCC is effective for selective fetal reduction in complicated monochorionic twin pregnancies.

Background. Gout is frequently accompanied by hypertension, obesity, and/or impaired glucose tolerance, which are often complicated with heavy smoking and dietary violations, especially in male patients.Objective. To determine the behavioral characteristics of gout patients that could impact the results of urate lowering therapy.Subjects and methods. The relationship between behavioral characteristics and results of urate lowering therapy were investigated in 74 male gout patients of Chengdu Rheumatism Hospital. The results of treatment were evaluated using serum uric acid contents before and after treatment, VAS pain score before and after treatment. Behavioral characteristics for the last ten years (smoking status, daily volume of drinking water, etc.) were accessed by means of retrospective survey.Results. In gout patients with poor treatment response, serum uric acid at the beginning of the treatment was already significantly lower (365.76 ± 163.06 μmol/L); this trend was also noted in a “slow progress” group, while patients with higher serum uric acid before treatment had notably better response to urate lowering therapy. During further analysis age negatively correlated with serum uric acid (r = –0.328; p = 0.002) and uric acid clearance ratio (r = –0.299; p = 0.002).In patients with uric acid clearance ratio above 40 % the prevalence of kidney diseases (stones or dysfunction) was significantly lower compared to other groups. There was no significant influence of hypertension, diabetes mellitus, fatty liver or hyperlipidaemia on uric acid clearance ratio (p > 0.05).Amount of drinking water also influenced the serum uric acid clearance ratio. Bigger amount of patients in the “fast progress” group (40.0 % compared to 30.44 and 25.0 %) tended to drink more water.Conclusion. In most gout patients, serum uric acid levels before treatment acted as the reliable predictor of good response to urate lowering therapy. Treatment response (serum uric acid clearance ratio) correlated positively with the hyperuricemia and drinking sufficient amounts of water, negatively – with prolonged smoking (more than 10 years) and age.

Background Regulatory T (Treg) cells play an essential role in peripheral immune tolerance. Bullous pemphigoid (BP) is the most common blistering disease and is caused by autoantibodies to two BP antigens: type XVII collagen and BP230. Recently, we reported that Treg cell dysfunction may cause the production of autoantibodies to BP antigens. Several studies have suggested an association between Treg cells and BP pathogenesis. However, Treg cells are heterogeneous in humans, leading to inconsistent results in previous studies. Objective To assess functional Treg subsets in BP. Methods We examined three distinct Treg subsets in conventional BP (cBP) patients before versus after systemic corticosteroid treatment, dipeptidyl peptidase-4 inhibitor-associated BP (DPP-4i-BP) patients, younger controls and older controls. Results We found that total Treg cells and all Treg cell subsets were increased in cBP patients before treatment and decreased by systemic corticosteroid treatment. In contrast, neither total Treg cells nor all Treg subsets were increased in DPP-4i-BP. Notably, CD45RA− Foxp3hi effector Treg cells positively correlated with disease severity in cBP, whereas CD45RA+Foxp3lo naive Treg cells positively correlated with the disease severity in DPP-4i-BP. Conclusion These findings suggest that Treg cells are differently involved in the pathogeneses of cBP and DPP-4i-BP.

Melatonin receptor type 1 (MTNR1A or MT1) is known to play an important role in cancer progression; however, its prognostic value for resected gastric adenocarcinoma (RGA) is unknown. In this study, we examined the potential of MT1 as a prognostic biomarker for RGA. The expression of the MT1 was evaluated in 67 patients with RGA by immunohistochemistry, and the relationship between MT1 levels and RGA prognosis was analyzed by Chi-square test, multivariate Cox regression, Kaplan-Meier method, and log-rank test. High MT1 expression was associated with a poor survival rate (29.0%, p=0.002) and the occurrence of metastasis (62.9%, p=0.004). Kaplan-Meier survival analysis and log rank tests revealed that patients with high expression of the MT1 had significantly shorter median overall survival compared to those with low expression (33.0 vs. 65.0 months, respectively; p=0.02). Multivariate Cox analysis indicated that the calculated death risk (hazard ratio [HR]) in patients with high expression levels of the MT1 increased to 2.68 (95% confidence interval [CI] 1.21-5.94, p=0.015), which was higher compared to those with low levels. HR of death was also high in patients with advanced T stage (2.51; 95 % CI 1.00-6.26, p=0.049) and metastasis (5.02; 95% CI 1.94-13.03, p=0.001). Our results showed that high MT1 expression in primary gastric adenocarcinoma tissues was associated with the occurrence of metastasis and poor prognosis. It may have prognostic significance as a potential biomarker in patients with RGA.

Objective This investigation assessed the profibrotic role that extracellular histones play in the pathogenesis of coal workers' pneumoconiosis (CWP). Methods The correlation of extracellular histones with small opacity profusion (SOP) and transforming growth factor-β (TGF-β) was analyzed. The stimulating effect of extracellular histones on pulmonary fibroblast was assessed in vitro. Results The levels of extracellular histones in plasma were positively correlated with SOP and TGF-β in the coal miners investigated. Plasma collected from patients with CWP caused apparent lung fibroblast proliferation, while anti-H4 antibody antagonized the stimulating effect of the patient plasma by blocking histone H4. In vitro experiments showed that extracellular histones directly stimulated fibroblast proliferation. Conclusion Consistent with our hypothesis, the concentrations of extracellular histones were indices of the severity of pulmonary fibrosis in simple CWP, and extracellular histones-targeted intervention could inhibit the proliferation of lung fibroblast.

Owing to their capacity to rapidly spread across the population, airborne pathogens represent a significant risk to global health. Indeed, several of the past major global pandemics have been instigated by respiratory pathogens. A greater understanding of the immune cells tasked with protecting the airways from infection will allow for the development of strategies that curb the spread and impact of these airborne diseases. A specific subset of memory T-cell resident in both the upper and lower respiratory tract, termed tissue-resident memory (Trm), have been shown to play an instrumental role in local immune responses against a wide breadth of both viral and bacterial infections. In this review, we discuss factors that influence respiratory tract Trm development, longevity, and immune surveillance and explore vaccination regimes that harness these cells, such approaches represent exciting new strategies that may be utilized to tackle the next global pandemic.

Rationale: The novel coronavirus disease-19 (COVID-19) has presented major challenges for global health systems. Given limited availability of diagnostic testing and delays in test results during the first wave of the pandemic, our hospital used computed tomography (CT) to risk stratify patients with suspected COVID-19. The aim of this study was to describe the various patterns of disease on chest CT and relate them to chest x-ray (CXR) findings. Methods: This is a retrospective review of 559 symptomatic patients infected with COVID-19 (diagnosed by real-time reverse transcription polymerase chain reaction) admitted from March 2020 to May 2020 at Temple University Hospital (Philadelphia, PA) who received admission CXR and chest CT scans that were performed within 24 hours of admission. Scans were independently reviewed by a group of radiologists. CXRs was interpreted as “consistent with COVID-19” if there were lower lobe peripheral opacities. Chest CTs were evaluated for the presence of ground glass opacities, consolidations, interlobular septal thickening, centrilobular nodules, and crazy paving pattern. Chest CT was also assessed for background lung disease (emphysema, interstitial lung disease). Results: Of the 559 patients, median age was 58 years old, 55.5% were female, and 56.7% were African American. Median BMI was 31.61. Median duration of symptoms at time of chest imaging was 5 days. 153 (27.4%) of patient's admission CXR was not consistent with COVID-19. Of those, 124 (81%) had abnormalities on chest CT. Median number of lobes involved with disease on CT was 3.8 and 317 patients (56.7%) had all 5 lobes with disease. The most common abnormalities found were ground glass opacities (n=507, 90.7%), consolidations (n=224, 40%) and centrilobular nodules (n=127, 22.7%). Less common findings included pleural effusion (n=62, 11.8%), lymphadenopathy (n=55, 9.8%), pericardial effusion (n=24, 4.2%), and pneumothorax (n=3, 0.53%). Of note, 82 (14.7%) patients were found to have emphysema, and 2 (0.35%) were found to have interstitial lung disease. Conclusion: We present one of the largest reviews of CT scans in patients admitted for COVID-19. The majority of our population had significant burden of disease on CT at time of presentation. Ground glass opacities and consolidations were the predominant findings. Most patients did not have background emphysema or interstitial lung disease. The fact that many patients with normal CXR had abnormalities on chest CT highlights the utility of chest CT in evaluating patients with COVID-19.

Rationale: The novel coronavirus disease-19 (COVID-19) has overwhelmed global healthcare systems. It would be beneficial to identify clinical signs that predict adverse outcomes to anticipate clinical deterioration and optimize management. COVID-19 has presented with a variety of patterns on computed tomography (CT) and these findings may assist in disease stratification. This study aims to identify potential CT characteristics that may portend adverse outcomes. Methods: This is a retrospective review of 559 symptomatic patients infected with COVID-19 admitted from March 2020 to May 2020 at Temple University Hospital (Philadelphia, PA) who received thorax CT scans on admission. These scans were independently reviewed by a chest radiologist and evaluated for the presence of ground glass opacities, consolidations, interlobular septal thickening, enlarged pulmonary artery (PA) diameter, centrilobular nodules, and crazy paving pattern. Common CT findings were then associated with a combined adverse inpatient outcome (requiring high-flow oxygen, mechanical ventilation, and/or death) through univariate and multivariate logistic regression. Results: Of the 559 patients, 182 (32.6%) required high-flow oxygen, mechanical ventilation, and/or died. The cohort with adverse outcomes were older (mean age 65.0 years vs 56.7 years, p

Rationale: Coronavirus disease 2019 (COVID-19) has provoked an unprecedented global pandemic. Invasive mechanical ventilation (IMV) rates in COVID-19 have been reported to be from 2.3% to 33%. The wide range in reported intubation rates is attributed in part to diverging institutional practices for the care of patients presenting with hypoxemic respiratory failure. The role of high flow nasal therapy (HFNT) in the treatment of COVID-19 has been controversial and underreported. Objectives: To report a retrospective analysis comparing the outcomes of patients treated with HFNT and IMV for hypoxemic respiratory failure secondary to COVID-19. Methods: This was an analysis of consecutive patients admitted to Temple University Hospital between March 10, 2020, and May 17, 2020, for moderate to severe hypoxemic respiratory failure from COVID-19 pneumonia. Patients were divided into three groups: IMV group-not placed on HFNT prior to intubation. HFNT group-received only HFNT. HFNT to intubation group-received HFNT prior to intubation. Comparisons were made between demographics, baseline laboratory values, and outcomes. Results: 1396 patients admitted to Temple University Hospital between March 10, 2020, and May 17, 2020 with suspected COVID-19 infection were retrospectively screened for this study. 837 patients tested positive for COVID-19 by nasopharyngeal RT-PCR or deemed positive based on clinical features. There were no statistically significant differences in terms of demographics between all three groups. However, the intubation and HFNT to intubation groups had a higher incidence of malignancy compared to the HFNT only group. There was a higher incidence of smoking in the intubation group (59.2%) and HFNT to intubation group (53.7%) compared to HFNT only group (29.2%). Laboratory data were similar between all three groups besides admission BUN/creatinine. In terms of therapies, high-dose steroids were administered more frequently to patients in the HFNT (84.3%) and HFNT to intubation (90.2%) groups compared to the intubated group (56.5%). Overall, 49 (28.1%) were intubated, 84 (48.2%) were treated with HFNT only, and 41 (23.5%) progressed from HFNT to intubation. The mortality was 36.7% in the intubation group, 6% in the HFNT only group, and 43.9% in the HFNT to intubation group. Overall mortality was 25.7%. Conclusion: Our institutional decision to utilize HFNT as the primary treatment for moderate to severe hypoxemic respiratory failure led to a low intubation rate thus reducing overall morbidity and mortality. In the appropriate clinical context HFNT should be the considered the oxygen modality of choice in moderate to severe hypoxemic respiratory failure secondary to COVID-19 pneumonia.

BackgroundSurges in COVID-19 disease cases can rapidly overwhelm healthcare resources; triaging to appropriate levels of care can assist in resource planning. At the beginning of the pandemic, we developed a simple triage tool, the Temple COVID-19 Pneumonia Triage Tool (TemCOV) based on a combination of clinical and radiographic features that are readily available on presentation to categorize and predict illness severity.MethodsWe prospectively examined 579 sequential cases admitted to Temple University Hospital who were assigned severity categories on admission. Our primary outcome was to compare the performance of TemCOV in predicting patients who have the highest likely of admission to the ICU at 24 and at 72 hours to other standard triage tools: the National Early Warning System (NEWS), the Modified Early Warning System (MEWS) and the CURB65 score. Additional endpoints included need for invasive mechanical ventilation (IMV) within 72 hours, total hospital admission charges, and mortality.Results26% of patients fell within our highest risk Category 4 and were more likely to require ICU admission at 24 hours (OR 11.51) and 72 hours (OR 8.6). Additionally they had the highest likelihood of needing IMV (OR 29.47) and in-hospital mortality (OR 2.37)., TemCOV performed similar to MEWS in predicting ICU admission at 24 hours (receive operator characteristic (ROC) curve area under the curve (AUC) 0.77 vs. 0.74, p=0.21) but better than NEWS2 and CURB65 (ROC AUC 0.77 vs. 0.69 and 0.77 vs. 0.64, respectively, pConclusionTemCOV is a simple triage score that can be used upon hospitalization in patients with COVID-19 that predicts the need for hospital resources such as ICU bed capacity, invasive mechanical ventilation and personnel staffing.

Red blood cells (RBCs) are biocompatible carriers that can be employed to deliver different bioactive substances. In the past few decades, many strategies have been developed to encapsulate or attach drugs to RBCs. Osmotic-based encapsulation methods have been industrialized recently, and some encapsulated RBC formulations have reached the clinical stage for treating tumors and neurological diseases. Inspired by the intrinsic properties of intact RBCs, some advanced delivery strategies have also been proposed. These delivery systems combine RBCs with other novel systems to further exploit and expand the application of RBCs. This review summarizes the clinical progress of drugs encapsulated into intact RBCs, focusing on the loading and clinical trials. It also introduces the latest advanced research based on developing prospects and limitations of intact RBCs drug delivery system (DDS), hoping to provide a reference for related research fields and further application potential of intact RBCs based drug delivery system.

BACKGROUND Venous thromboembolism (VTE) post lung transplantation is common and has been associated with worse post transplant survival . We report a comprehensive single center review of VTE incidence in the first post transplant year, investigate modifiable risk factors and assess impact on short term outcomes. METHODS Retrospective review of all lung transplant recipients between August 2016 to 2018 at Temple University Hospital. Patients were followed for 1 year post transplant. All patients were screened for deep venous thrombosis (DVT) within the first 2 weeks with a venous duplex study. Pre transplant, intra operative, post operative variables, and peri-operative practice patterns were compared between VTE positive and VTE negative groups. Logistic regression modeling was used to identify risk factors for early VTE (VTE within 30 days after transplant). RESULTS A total of 235 patients were included in the study, 58 patients (24.7%) developed a VTE in the first post transplant year. Median time to diagnosis was 17 days. Of the patients with VTE, 76% had an isolated DVT, 13.5 % had an isolated pulmonary embolism (PE), and 10.3% had concomitant DVT and PE. In a multivariate logistic regression model, cardiopulmonary bypass (CPB) (OR 1.93 p = 0.015) and interruption of VTE prophylaxis (OR 4.42 p CONCLUSION VTE post lung transplant is common despite the use of prophylactic anticoagulation . CPB use and interruption of DVT prophylaxis are risk factors for early post transplant VTE. Measures to ensure consistent and uninterrupted prophylaxis may help decrease VTE incidence after lung transplantation.

Background: Determine the impact of tobacco smoking status on patients hospitalized with COVID-19 pneumonia in the need for ICU care, mechanical ventilation and mortality. Methods: We performed a retrospective cohort study, that involved chart review. All adults 18 years or older with a diagnosis of COVID-19 pneumonia hospitalized from March 15th, 2020 to May 06th, 2020 with a positive reverse transcription polymerase chain reaction (RT-PCR) nasopharyngeal swab for COVID-19. We used chi-squared test for categorical variables and student t-tests or Wilcoxon rank sum tests for continuous variables. We further used adjusted and unadjusted logistic regression to assess risk factors for mortality and intubation.Results: Among 577 patients hospitalized with COVID-19 pneumonia, 268 (46.4%) had a history of smoking including 187 former and 81 active smokers. The former smokers when compared with non-smokers were predominantly older with more comorbidities. Also, when compared with never smokers D Dimer levels were elevated in active (p=0.05) and former smokers (pConclusions: In our cohort of hospitalized patients with COVID-19 pneumonia, former smokers had higher need for non-invasive respiratory support on admission, ICU care, and mortality compared to non-smokers. Also, active smokers versus non-smokers needed more mechanical ventilation.

Introduction Use of high flow nasal therapy (HFNT) to treat COVID-19 pneumonia has been greatly debated around the world due to concern for increased healthcare worker transmission and delays in invasive mechanical Ventilation (IMV). Herein we analyze the utility of the ROX index to predict the need and timing for IMV in a retrospective analysis of patients with COVID-19 with moderate to severe hypoxemic respiratory failure treated with HFNT. Methods This was a retrospective analysis of 129 consecutive patients with COVID-19 admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to May 17, 2020 with moderate to severe hypoxemic respiratory failure treated with High Flow nasal therapy (HFNT). HFNT patients were divided into two groups: HFNT only and HFNT progressed to IMV. The primary outcome was the ability of the ROX index to predict the need of IMV. Secondary outcomes were mortality, rates of intubation, length of stay (LOS) and rates of nosocomial infections in our cohort treated with HFNT were also reported. Results 837 patients with COVID-19 were screened, 129 met inclusion criteria. The mean age was 60.8(+13.6) years, BMI 32.6(+8), 58(45 %) were female, 72(55.8%) were African American, 40 (31%) Hispanic. 48 (37.2%) were smokers. Of the 129, 89 were HFNT only group whereas 40 in the HFNT progressed to IMV group. Mean time to intubation was 2.5 days(+ 3.3). The 89 HFNT only patients had a significant improvement in ROX from initiation of HFNT at all recorded time points. In contrast, the ROX in HFNT progressed to IMV patients remained unchanged or decreased over time. ROX index of less than 5 at HFNT initiation was predictive of progression to IMV (OR = 2.137, p = 0,052). Any decrease in ROX index after HFNT initiation was predictive of intubation (OR= 14.67, p 0), peak D-dimer >4000 and admission GFR < 60 ml/min were very strongly predictive of need for IMV (ROC = 0.86, p=0.001). Mortality was 11.2% in HFNT only group versus 47.5% in the HFNT progressed to IMV group (p = 0.0001). Mortality and need for pulmonary vasodilators were higher in the HNFT progressed to IMV group. Conclusion ROX index is a valuable, noninvasive tool to evaluate patients with moderate to severe hypoxemic respiratory failure in COVID-19 treated with HFNT. ROX helps predicts need for IMV and thus limiting morbidity and mortality associated with IMV.

IntroductionCurrently the main diagnostic modality for COVID-19 (Coronavirus disease-2019) is reverse transcriptase polymerase chain reaction (RT-PCR) via nasopharyngeal swab which has high false negative rates. We evaluated the performance of high-resolution computed tomography (HRCT) imaging in the diagnosis of suspected COVID-19 infection compared to RT-PCR nasopharyngeal swab alone in patients hospitalized for suspected COVID-19 infection.MethodsThis was a retrospective analysis of 324 consecutive patients admitted to Temple University Hospital. All hospitalized patients who had RT-PCR testing and HRCT were included in the study. HRCTs were classified as Category 1, 2 or 3. Patients were then divided into four groups based on HRCT category and RT-PCR swab results for analysis.ResultsThe average age of patients was 59.4 (±15.2) years and 123 (38.9%) were female. Predominant ethnicity was African American 148 (46.11%). 161 patients tested positive by RT-PCR, while 41 tested positive by HRCT. 167 (52.02%) had category 1 scan, 63 (19.63%) had category 2 scan and 91 (28.35%) had category 3 HRCT scans. There was substantial agreement between our radiologists for HRCT classification (κ = 0.64). Sensitivity and specificity of HRCT classification system was 77.6 and 73.7 respectively. Ferritin, LDH, AST and ALT were higher in Group 1 and D-dimers levels was higher in Group 3; differences however were not statistically significant.ConclusionDue to its high infectivity and asymptomatic transmission, until a highly sensitive and specific COVID-19 test is developed, HRCT should be incorporated into the assessment of patients who are hospitalized with suspected COVID-19.Key PointsKey QuestionCan High Resolution CT chest (HRCT) improve diagnostic accuracy of current Nasopharyngeal swab in suspected COVID-19 patients?Bottom LineIn this retrospective analysis, our novel HRCT classification identified 20% of all COVID-19 patients who had negative nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) tests but had HRCT findings consistent with COVID-19 pneumonia. These patients were ruled out for other infections and laboratory markers were similar to other RT-PCR positive patientsWhy Read onOur new HRCT classification when combined with RT-PCR can improve diagnostic accuracy while promptly improving triaging in COVID-19 patients.

Open biomass burning (OBB) has significant impacts on air pollution, climate change and potential human health. OBB has gathered wide attention but with little focus on the annual variation of pollutant emission. Central and eastern China (CEC) is one of the most polluted regions in China. This study aims to provide a state-of-the-art estimation of the pollutant emissions from OBB in CEC from 2003 to 2015, by adopting the satellite observation dataset – the burned area product (MCD64Al) and the active fire product (MCD14 ML) – along with local biomass data (updated biomass loading data and high-resolution vegetation data) and local emission factors. The successful adoption of the double satellite dataset for long-term estimation of pollutants from OBB with a high spatial resolution can support the assessing of OBB on regional air quality, especially for harvest periods or dry seasons. It is also useful to evaluate the effects of annual OBB management policies in different regions. Here, monthly emissions of pollutants were estimated and allocated into a 1×1 km spatial grid for four types of OBB including grassland, shrubland, forest and cropland. From 2003 to 2015, the emissions from forest, shrubland and grassland fire burning had an annual fluctuation, whereas the emissions from crop straw burning steadily increased. The cumulative emissions of organic carbon (OC), elemental carbon (EC), methane (CH4), nitric oxide (NOx), non-methane volatile organic compounds (NMVOCs), sulfur dioxide (SO2), ammonia (NH3), carbon monoxide (CO), carbon dioxide (CO2) and fine particles (PM2.5) were 3.64×103, 2.87×102, 3.05×103, 1.82×103, 6.4×103, 2.12×102, 4.67×102, 4.59×104, 9.39×105 and 4.13×103 Gg in these years, respectively. Crop straw burning was the largest contributor for all pollutant emissions, by 84 %–96 %. For the forest, shrubland and grassland fire burning, forest fire burning emissions contributed the most, and emissions from grassland fire were negligible due to little grass coverage in this region. High pollutant emissions concentrated in the connection area of Shandong, Henan, Jiangsu and Anhui, with emission intensity higher than 100 tons per square kilometer, which was related to the frequent agricultural activities in these regions. Peak emission of pollutants occurred during summer and autumn harvest periods including May, June, September and October, during which ∼ 50 % of the total pollutant emissions were emitted in these months. This study highlights the importance of controlling the crop straw burning emissions. From December to March, the crop residue burning emissions decreased, while the emissions from forest, shrubland and grassland exhibited their highest values, leading to another small peak in emissions of pollutants. Obvious regional differences in seasonal variations of OBB were observed due to different local biomass types and environmental conditions. Rural population, agricultural output, economic levels, local burning habits, social customs and management policies were all influencing factors for OBB emissions.

Background The use of high-flow nasal therapy (HFNT) to treat COVID-19 pneumonia has been greatly debated around the world due to concerns about increased health care worker transmission and delays in invasive mechanical ventilation (IMV). Herein, we analyzed the utility of the noninvasive ROX (ratio of oxygen saturation) index to predict the need for and timing of IMV. Objective This study aimed to assess whether the ROX index can be a useful score to predict intubation and IMV in patients receiving HFNT as treatment for COVID-19–related hypoxemic respiratory failure. Methods This is a retrospective cohort analysis of 129 consecutive patients with COVID-19 admitted to Temple University Hospital in Philadelphia, PA, from March 10, 2020, to May 17, 2020. This is a single-center study conducted in designated COVID-19 units (intensive care unit and other wards) at Temple University Hospital. Patients with moderate and severe hypoxemic respiratory failure treated with HFNT were included in the study. HFNT patients were divided into two groups: HFNT only and intubation (ie, patients who progressed from HFNT to IMV). The primary outcome was the value of the ROX index in predicting the need for IMV. Secondary outcomes were mortality, rate of intubation, length of stay, and rate of nosocomial infections in a cohort treated initially with HFNT. Results Of the 837 patients with COVID-19, 129 met the inclusion criteria. The mean age was 60.8 (SD 13.6) years, mean BMI was 32.6 (SD 8) kg/m², 58 (45%) were female, 72 (55.8%) were African American, 40 (31%) were Hispanic, and 48 (37.2%) were nonsmokers. The mean time to intubation was 2.5 (SD 3.3) days. An ROX index value of less than 5 at HFNT initiation was suggestive of progression to IMV (odds ratio [OR] 2.137, P=.052). Any further decrease in ROX index value after HFNT initiation was predictive of intubation (OR 14.67, P Conclusions The ROX index helps decide which patients need IMV and may limit eventual morbidity and mortality associated with the progression to IMV.

Cytochrome P450s (CYPs or P450s) have been long recognized as very important enzymes in the metabolism of xenobiotic and endogenous compounds, but only a few CYPs have been functionally characterized in insects. The effort in functional characterization of insect P450s is heavily hindered by technical difficulties in preparing active, individual P450 enzymes directly from the target insect. In this paper, we describe the functional expression of two additional pyrethroid resistance-associated CYP9A genes (CYP9A12andCYP9A17) from the polyphagous pestHelicoverpa armigerain the facileEscherichia coli. The functionality ofE. coliproduced CYP9A12, CYP9A14, and CYP9A17 was investigated and activities of these CYP9As were compared against three probe substrates after reconstitution with NADPH-dependent cytochrome P450 reductase. The results showed that active forms of CYP9A12 and CYP9A17 were expressed inE. coliwith a content of about 1.0–1.5 nmol mg−1protein in membrane preparations.In vitroassays showed that CYP9A14 was capable of catalyzing O-dealkylation of methoxyresorufin (MROD), ethoxyresorufin (EROD), and benzyloxyresorufin (BROD), while CYP9A12 and CYP9A17 exhibited only MROD and EROD activities. Kinetic studies demonstrated that CYP9A14 had the greatestkcat/Kmvalue for MROD, and CYP9A17 for EROD, while the lowestkcat/Kmvalues for both MROD and EROD were observed for CYP9A12. The distinct biochemical traits suggest that the three paralogous CYP9As may play different roles in xenobiotic metabolism in this important pest.

Structured AbstractObjectives The objective of this study was to perform a systematic review of the orthodontic literature with regard to efficiency, effectiveness and stability of treatment outcome with clear aligners compared with treatment with conventional brackets. Methods An electronic search without time or language restrictions was undertaken in October 2014 in the following electronic databases: Google Scholar, the Cochrane Oral Health Group's Trials Register, Scopus, CENTRAL, MEDLINE via OVID, EMBASE via OVID and Web of Science. We also searched the reference lists of relevant articles. Quality assessment of the included articles was performed. Two authors were responsible for study selection, validity assessment and data extraction. Results Four controlled clinical trials including a total of 252 participants satisfied the inclusion criteria. We grouped the trials into four main comparisons. One randomized controlled trial was classified as level 1B evidence, and three cohort studies were classified as level 2B evidence. Clear aligners appear to have a significant advantage with regard to chair time and treatment duration in mild-to-moderate cases based on several cross-sectional studies. No other differences in stability and occlusal characteristics after treatment were found between the two systems. Conclusions Despite claims about the effectiveness of clear aligners, evidence is generally lacking. Shortened treatment duration and chair time in mild-to-moderate cases appear to be the only significant effectiveness of clear aligners over conventional systems that are supported by the current evidence.

Rosuvastatin is a frequently used probe in transporter-mediated drug-drug interaction (DDI) studies. This report describes the development of a physiologically based pharmacokinetic (PBPK) model of rosuvastatin for prediction of pharmacokinetic (PK) DDIs. The rosuvastatin model predicted the observed single (i.v. and oral) and multiple dose PK profiles, as well as the impact of coadministration with transporter inhibitors. The predicted effects of rifampin and cyclosporine (6.58-fold and 5.07-fold increase in rosuvastatin area under the curve (AUC), respectively) were mediated primarily via inhibition of hepatic organic anion-transporting polypeptide (OATP)1B1 (Inhibition constant (Ki ) ∼1.1 and 0.014 µM, respectively) and OATP1B3 (Ki ∼0.3 and 0.007 µM, respectively), with cyclosporine also inhibiting intestinal breast cancer resistance protein (BCRP; Ki ∼0.07 µM). The predicted effects of gemfibrozil and its metabolite were moderate (1.88-fold increase in rosuvastatin AUC) and mediated primarily via inhibition of hepatic OATP1B1 and renal organic cation transporter 3. This model of rosuvastatin will be useful in prospectively predicting transporter-mediated DDIs with novel pharmaceutical agents in development.