Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis.

Coccidioides is an endemic fungus that causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016 and 2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months, and 9 months post-transplant, patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (P = 0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.

Solid organ transplant recipients can be highly immune suppressed, and infection with Coccidioides (valley fever) after transplant can lead to severe infections in these patients. Our study showed that fluconazole was safe and effective for preventing Coccidioides in kidney transplant recipients.

Maternal and Fetal Radiation-Induced Cancer Risk From Computed Tomography Pulmonary Angiography During Pregnancy: A Retrospective Cohort Study Across a Multihospital Integrated Health Care Network.

OBJECTIVE: Computed tomography pulmonary angiogram (CTPA) is important to evaluate suspected pulmonary embolism in pregnancy but has maternal/fetal radiation risks. The objective of this study was to estimate maternal and fetal radiation-induced cancer risk from CTPA during pregnancy. METHODS: Simulation modeling via the National Cancer Institute's Radiation Risk Assessment Tool was used to estimate excess cancer risks from 17 organ doses from CTPA during pregnancy, with doses determined by a radiation dose indexing monitoring system. Organ doses were obtained from a radiation dose indexing monitoring system. Maternal and fetal cancer risks per 100,000 were calculated for male and female fetuses and several maternal ages. RESULTS: The 534 CTPA examinations had top 3 maternal organ doses to the breast, lung, and stomach of 17.34, 15.53, and 9.43 mSv, respectively, with a mean uterine dose of 0.21 mSv. The total maternal excess risks of developing cancer per 100,000 were 181, 151, 121, 107, 94.5, 84, and 74.4, respectively, for a 20-, 25-, 30-, 35-, 40-, 45-, and 50-year-old woman undergoing CTPA, compared with baseline cancer risks of 41,408 for 20-year-old patients. The total fetal excess risks of developing cancer per 100,000 were 12.3 and 7.3 for female and male fetuses, respectively, when compared with baseline cancer risks of 41,227 and 48,291. DISCUSSION: Excess risk of developing cancer from CTPA was small relative to baseline cancer risk for pregnant patients and fetuses, decreased for pregnant patients with increasing maternal age, and was greater for female fetuses than male fetuses.

First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody.

With most of the T cells residing in the tissue, not the blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics is important for studying their role in immune response and memory. This study presents the first use of dynamic positron emission tomography (PET) and kinetic modeling for in vivo measurement of CD8+ T cell biodistribution in humans. A 89Zr-labeled CD8-targeted minibody (89Zr-Df-Crefmirlimab) was used with total-body PET in healthy individuals (N = 3) and coronavirus disease 2019 (COVID-19) convalescent patients (N = 5). Kinetic modeling results aligned with T cell-trafficking effects expected in lymphoid organs. Tissue-to-blood ratios from the first 7 hours of imaging were higher in bone marrow of COVID-19 convalescent patients compared to controls, with an increasing trend between 2 and 6 months after infection, consistent with modeled net influx rates and peripheral blood flow cytometry analysis. These results provide a promising platform for using dynamic PET to study the total-body immune response and memory.

Prevalence of Comorbid Factors in Patients With Recurrent Clostridioides difficile Infection in ECOSPOR III, a Randomized Trial of an Oral Microbiota-Based Therapeutic.

BACKGROUND: Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter "VOS," formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI. METHODS: Adults with rCDI were randomized to receive VOS or placebo (4 capsules daily for 3 days) following standard-of-care antibiotics. In this post hoc analysis, the rate of rCDI through week 8 was assessed in VOS-treated participants compared with placebo for subgroups including (i) Charlson comorbidity index (CCI) score category (0, 1-2, 3-4, ≥5); (ii) baseline creatinine clearance (<30, 30-50, >50 to 80, or >80 mL/minute); (iii) number of CDI episodes, inclusive of the qualifying episode (3 and ≥4); (iv) exposure to non-CDI-targeted antibiotics after dosing; and (v) acid-suppressing medication use at baseline. RESULTS: Of 281 participants screened, 182 were randomized (59.9% female; mean age, 65.5 years). Comorbidities were common with a mean overall baseline age-adjusted CCI score of 4.1 (4.1 in the VOS arm and 4.2 in the placebo arm). Across all subgroups analyzed, VOS-treated participants had a lower relative risk of recurrence compared with placebo. CONCLUSIONS: In this post hoc analysis, VOS reduced the risk of rCDI compared with placebo, regardless of baseline characteristics, concomitant medications, or comorbidities.

A predictive model for lung cancer screening nonadherence in a community setting health-care network.

BACKGROUND: Lung cancer screening (LCS) decreases lung cancer mortality. However, its benefit may be limited by nonadherence to screening. Although factors associated with LCS nonadherence have been identified, to the best of our knowledge, no predictive models have been developed to predict LCS nonadherence. The purpose of this study was to develop a predictive model leveraging a machine learning model to predict LCS nonadherence risk. METHODS: A retrospective cohort of patients who enrolled in our LCS program between 2015 and 2018 was used to develop a model to predict the risk of nonadherence to annual LCS after the baseline examination. Clinical and demographic data were used to fit logistic regression, random forest, and gradient-boosting models that were internally validated on the basis of accuracy and area under the receiver operating curve. RESULTS: A total of 1875 individuals with baseline LCS were included in the analysis, with 1264 (67.4%) as nonadherent. Nonadherence was defined on the basis of baseline chest computed tomography (CT) findings. Clinical and demographic predictors were used on the basis of availability and statistical significance. The gradient-boosting model had the highest area under the receiver operating curve (0.89, 95% confidence interval = 0.87 to 0.90), with a mean accuracy of 0.82. Referral specialty, insurance type, and baseline Lung CT Screening Reporting & Data System (LungRADS) score were the best predictors of nonadherence to LCS. CONCLUSIONS: We developed a machine learning model using readily available clinical and demographic data to predict LCS nonadherence with high accuracy and discrimination. After further prospective validation, this model can be used to identify patients for interventions to improve LCS adherence and decrease lung cancer burden.

Patient and Fetal Radiation-Induced Malignancy Risk From Imaging For Evaluation of Pulmonary Embolism in Pregnancy.

BACKGROUND: Imaging for diagnosis of suspected pulmonary embolism in pregnancy presents radiation concerns for patient and fetus. OBJECTIVES: Estimate the risks of radiation-induced breast cancer and childhood leukemia from common imaging techniques for the evaluation of suspected pulmonary embolism in pregnancy. METHODS: Breast and uterine absorbed doses for various imaging techniques were input into the National Cancer Institute Radiation Risk Assessment Tool to calculate risk of breast cancer for the patient and childhood leukemia for the fetus. Absorbed doses were obtained by synthesizing data from a recent systematic review and the International Commission on Radiological Protection. Primary outcomes were the estimated excess incidences of breast cancer and childhood leukemia per 100,000 exposures. RESULTS: Baseline incidences of breast cancer for a 30-year-old woman and childhood leukemia for a male fetus were 13,341 and 939, respectively. Excess incidences of breast cancer were 0.003 and 0.275 for a single and two-view chest radiograph, respectively, 9.53 and 20.6 for low- and full-dose computed tomography pulmonary angiography (CTPA), respectively, 0.616 and 2.54 for low- and full-dose perfusion scan, respectively, and 0.732 and 2.66 for low- and full-dose ventilation perfusion scan, respectively. Excess incidences of childhood leukemia were 0.004 and 0.007 for a single and two-view chest radiograph, respectively, 0.069 and 0.490 for low- and full-dose CTPA, respectively, 0.359 and 1.47 for low- and full-dose perfusion scan, respectively, and 0.856 and 1.97 for low- and full-dose ventilation perfusion scan, respectively. CONCLUSION: Excess cancer risks for all techniques were small relative to baseline cancer risks, with CTPA techniques carrying slightly higher risk of breast cancer for the patient and ventilation perfusion techniques a higher risk of childhood leukemia.

Fluorescent Probes Based on AIEgen-Mediated Polyelectrolyte Assemblies for Manipulating Intramolecular Motion and Magnetic Relaxivity.

Uniting photothermal therapy (PTT) with magnetic resonance imaging (MRI) holds great potential in nanotheranostics. However, the extensively utilized hydrophobicity-driven assembling strategy not only restricts the intramolecular motion-induced PTT, but also blocks the interactions between MR agents and water. Herein, we report an aggregation-induced emission luminogen (AIEgen)-mediated polyelectrolyte nanoassemblies (APN) strategy, which bestows a unique "soft" inner microenvironment with good water permeability. Femtosecond transient spectra verify that APN well activates intramolecular motion from the twisted intramolecular charge transfer process. This de novo APN strategy uniting synergistically three factors (rotational motion, local motion, and hydration number) brings out high MR relaxivity. For the first time, APN strategy has successfully modulated both intramolecular motion and magnetic relaxivity, achieving fluorescence lifetime imaging of tumor spheroids and spatio-temporal MRI-guided high-efficient PTT.

Improvement in postoperative lung function in patients with moderate to severe airway obstruction after robotic-assisted thoracoscopic tracheobronchoplasty.

OBJECTIVE: The study objective was to examine pulmonary function and quality of life improvement after robotic-assisted thoracoscopic tracheobronchoplasty for patients with different degrees of obstructive airway disease. METHODS: We performed a retrospective review of a prospective database of patients who underwent robotic-assisted thoracoscopic tracheobronchoplasty between 2013 and 2020. RESULTS: A total of 118 patients underwent robotic-assisted thoracoscopic tracheobronchoplasty. Preoperative and postoperative pulmonary function tests were available for 108 patients. Postoperative pulmonary function tests at a median of 16 months demonstrated a significant increase in percent predicted forced expiratory volume in 1 second (preoperative median: 76.76% predicted, postoperative: 83% predicted, P = .002). Preoperative and postoperative St George Respiratory Questionnaires were available for 64 patients with a significant decrease in postoperative score at a median of 7 months (preoperative median: 61, postoperative: 41.60, P < .001). When stratified by preoperative degree of obstruction, robotic-assisted thoracoscopic tracheobronchoplasty improved forced expiratory volume in 1 second in moderate to very severe obstruction with a statistically significant improvement in moderate (preoperative median: 63.91% predicted, postoperative median: 73% predicted, P = .001) and severe (preoperative median: 44% predicted, postoperative median: 57% predicted, P = .007) obstruction. St George Respiratory Questionnaire scores improved for all patients. Improvement for mild (preoperative median: 61.27, postoperative median: 36.71, P < .001) and moderate (preoperative median: 57.15, postoperative median: 47.52, P = .03) obstruction was statistically significant. CONCLUSIONS: Robotic-assisted thoracoscopic tracheobronchoplasty improves obstruction and symptoms. With limited follow-up, subgroup analysis showed forced expiratory volume in 1 second improved in severe preoperative obstruction and quality of life improved in moderate obstruction. Future follow-up is required to determine robotic-assisted thoracoscopic tracheobronchoplasty effects on the most severe group, but we cannot conclude that increased degree of preoperative obstruction precludes surgery.

Achenbach syndrome: no need for skin biopsy.

As dermatologists with Achenbach syndrome, we argue against the need for skin biopsy to confirm the diagnosis in this benign condition.

Algorithmic Approach to the Diagnosis of Organizing Pneumonia: A Correlation of Clinical, Radiologic, and Pathologic Features.

Organizing pneumonia (OP), characterized histopathologically by patchy filling of alveoli and bronchioles by loose plugs of connective tissue, may be seen in a variety of conditions. These include but are not limited to after an infection, drug reactions, radiation therapy, and collagen vascular diseases. When a specific cause is responsible for this entity, it is referred to as "secondary OP." When an extensive search fails to reveal a cause, it is referred to as "cryptogenic OP" (previously called "bronchiolitis obliterans with OP"), which is a clinical, radiologic, and pathologic entity classified as an interstitial lung disease. The clinical presentation of OP often mimics that of other disorders, such as infection and cancer, which can result in a delay in diagnosis and inappropriate management of the underlying disease. The radiographic presentation of OP is polymorphous but often has subpleural consolidations with air bronchograms or solitary or multiple nodules, which can wax and wane. Diagnosis of OP sometimes requires histopathologic confirmation and exclusion of other possible causes. Treatment usually requires a prolonged steroid course, and disease relapse is common. The aim of this article is to summarize the clinical, radiographic, and histologic presentations of this disease and to provide a practical diagnostic algorithmic approach incorporating clinical history and characteristic imaging patterns.

Complex supramolecular fiber formed by coordination-induced self-assembly of benzene-1,3,5-tricarboxamide (BTA).

HYPOTHESIS: In the quest for large but well-controlled supramolecular structures, the discotic benzene-1,3,5-tricarboxamide (BTA) has received quite some attention, because it can form hydrogen-bonded stacks that can be regarded as supramolecular polymers of which the single BTA molecule is the monomer. In this report, we consider a more complex BTA-based supramolecular polymer, namely one that is built up from supramolecular 'monomers'. EXPERIMENTS: We design a tris-ligand L3 consisting of a BTA core carrying three dipicolinic acid (DPA) groups. L3 itself is too small to form polymers, but in the presence of appropriate metal ions, each L3 can form three coordination bonds and so form (L3)n clusters that are large enough to stack successfully: at an appropriate metal dose, long and stable filaments with a cross-sectional diameter of 12 nm appear. We monitor the growth process by UV-vis spectroscopy and light scattering, and use small angle X-ray scattering (SAXS), TEM as well as molecular simulation to confirm the filamentous structure of the fibers and determine their dimensions. FINDINGS: The formation and structure of the fiber are very similar for various transition metal ions, which enables introducing different functionalities, e.g., magnetic relaxivity, by proper choice of the metal ions. Hence, we obtain a doubly supramolecular polymer, connected axially by hydrogen bonds, and radially by coordination bonds. Not only does this realize a higher level of complexity, but it also allows to easily introduce and vary metal-derived functionalities.

Robotic-assisted tracheobronchoplasty: Quality of life and pulmonary function assessment on intermediate follow-up.

OBJECTIVE: The initial description of robotic tracheobronchoplasty for the treatment of tracheobronchomalacia demonstrated feasibility, safety, and short-term symptomatic and functional improvement. The purpose of the current study was to demonstrate intermediate outcomes in postoperative pulmonary function and quality of life after robotic tracheobronchoplasty. METHODS: We retrospectively reviewed prospectively collected clinical data from 42 patients who underwent robotic tracheobronchoplasty from May 2016 to December 2017. The Institutional Review Board or equivalent ethics committee of the Northwell Health approved the study protocol and publication of data. Patient written consent for the publication of the study data was waived by the Institutional Review Board. RESULTS: A total of 42 patients underwent robotic tracheobronchoplasty during the study period. Median total follow-up is 40 months. There was 1 death since surgery from an unrelated disease. Significant decreases in St George's Respiratory Questionnaire total score (preoperative mean: 64.01, postoperative mean: 38.91, P = .002), St George's Respiratory Questionnaire symptom score (preoperative median: 82.6, postoperative median: 43.99, P < .001), and St George's Respiratory Questionnaire impact score (preoperative median: 55.78, postoperative median: 25.95, P < .001) were apparent at a median follow-up of 13 months. Comparison of preoperative and postoperative pulmonary function tests revealed a significant increase in percent predicted forced expiratory volume in 1 second (preoperative median: 74% vs postoperative median: 82%, P = .001), forced vital capacity (preoperative median: 68.5% vs postoperative median: 80.63%, P < .001), and peak expiratory flow (preoperative median: 61.5% vs postoperative median: 75%, P = .02) measured at a median follow-up of 29 months. CONCLUSIONS: Robotic tracheobronchoplasty is associated with low intermediate-term mortality. Robotic tracheobronchoplasty results in significant improvement in quality of life and postoperative pulmonary function. Longer-term follow-up is necessary to continue to elucidate the effect of robotic tracheobronchoplasty on halting pathologic progression of tracheobronchomalacia and to determine the long-term impact of tracheobronchoplasty on symptomatic and functional improvement.

Comparison of Guidelines for Evaluation of Suspected Pulmonary Embolism in Pregnancy: A Cost-effectiveness Analysis.

BACKGROUND: Pulmonary embolism (PE) remains a leading cause of maternal mortality, yet diagnosis remains challenging. International diagnostic guidelines vary significantly in their recommendations, making it difficult to determine an optimal policy for evaluation. RESEARCH QUESTION: Which societal-level diagnostic guidelines for evaluation of suspected PE in pregnancy are an optimal policy in terms of its cost-effectiveness? STUDY DESIGN AND METHODS: We constructed a complex Markov decision model to evaluate the cost-effectiveness of each identified societal guidelines for diagnosis of PE in pregnancy. Our model accounted for risk stratification, empiric treatment, diagnostic testing strategies, as well as short- and long-term effects from PE, treatment with low-molecular-weight heparin, and radiation exposure from advanced imaging. We considered clinical and cost outcomes of each guideline from a US health care system perspective with a lifetime horizon. Clinical effectiveness and costs were measured in time-discounted quality-adjusted life years (QALYs) and US dollars, respectively. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $100,000/QALY. One-way, multiway, and probabilistic sensitivity analyses were performed. RESULTS: We identified six international societal-level guidelines. Base-case analysis showed the guideline proposed by the American Thoracic Society and Society of Thoracic Radiology (ATS-STR) yielded the highest health benefits (22.90 QALYs) and was cost-effective, with an ICER of $7,808 over the guidelines proposed by the Australian Society of Thrombosis and Haemostasis and the Society of Obstetric Medicine of Australia and New Zealand (ASTH-SOMANZ). All remaining guidelines were dominated. The ATS-STR guideline-recommended strategy yielded an expected additional 2.7 QALYs/100 patients evaluated over the ASTH-SOMANZ. Conclusions were robust to sensitivity analyses, with the ATS-STR guidelines optimal in 86% of probabilistic sensitivity analysis scenarios. INTERPRETATION: The ATS-STR guidelines for diagnosis of suspected PE in pregnancy are cost-effective and generate better expected health outcomes than guidelines proposed by other medical societies.

Factors Associated With Lung Cancer Screening Adherence Among Patients With Negative Baseline CT Results in a Community Health Care Setting.

PURPOSE: Lung cancer screening (LCS) decreases lung cancer mortality; however, that reduction depends upon screening adherence. The purpose of this study was to determine factors associated with adherence rate for LCS among patients with negative baseline CT results in a multi-integrated health care network. METHODS: A retrospective analysis was conducted among patients with negative baseline CT results in a multi-integrated health care network LCS program between January 2015 and January 2020. The two outcomes were adherence for the first and second subsequent LCS studies. Negative baseline result was defined as a Lung CT Screening Reporting and Data System score 0, 1, or 2. Adherence was defined as undergoing a follow-up study within 11 to 15 months of a prior scan. Multivariable logistic regression was used to determine significant predictors of adherence, adjusting for patient demographics, median household income (on the basis of geocoding ZIP codes from the US Census Bureau), smoking history, screening sites, and provider specialty. RESULTS: A total of 30.7% (512 of 1,668) and 16.3% (270 of 1,660) of patients were adherent for the first two annual subsequent screens, respectively. First-year adherence was higher among former smokers and varied by site and provider specialty. Second-year adherence was higher among former smokers and varied by site, provider specialty, and pack-years smoked. CONCLUSIONS: Adherence to LCS in a multihospital integrated health care network was poor and even lower at year 2. The identified factors associated with adherence may serve as targets to increase LCS adherence and decrease lung cancer mortality.

CT pulmonary angiography in pregnancy: Specific conversion factors to estimate effective radiation dose from dose length product: A retrospective cross-sectional study across a multi-hospital integrated healthcare network.

PURPOSE: Effective dose describes radiation-related cancer risk from CT scans and is estimated using a readily available conversion factor (k-factor), which varies by body part and study type. To purpose of this study is to determine the specific k-factor for CTPA in pregnant patients and its predictive factors. METHODS: This retrospective cross-sectional study evaluates CTPA in pregnancy across a multihospital integrated healthcare network from January 2012 to April 2017. Patient and CTPA-related data were obtained from the electronic health record and a radiation dose index monitoring system. Each patient's effective dose was determined by patient-specific Monte-Carlo simulation with Cristy phantoms and divided by patient dose-length-product to determine the k-factor. K-factor for pregnant patients was compared to the k-factor for adults of standard physique with a one-sample t-test. Bivariate and multivariable analyses were performed for patient and CT predictors of k-factor. RESULTS: A total of 534 patients were included. The mean k-factor for all patients was 0.0249 (mSv·mGy-1·cm-1), 78% greater than k-factor of 0.014 (p < 0.001) suggested for the general adult population. Multivariable analysis demonstrated lower k-factors with increasing pitch (p = 0.0002), patient size (p < 0.001), and scan length (p < 0.0001). The 120 kVp (p < 0.001) and 140 kVp (p = 0.0028) analyses showed a larger k-factor than 80 and 100 kVp studies combined. CONCLUSIONS: Specific k-factor for CTPA in pregnant patients is greater than the previously used generic chest CT k-factor and should be used to estimate the effective dose for CTPA exams in pregnancy.

Supramolecular virus-like particles by co-assembly of triblock polypolypeptide and PAMAM dendrimers.

Virus-like particles are of special interest as functional delivery vehicles in a variety of fields ranging from nanomedicine to materials science. Controlled formation of virus-like particles relies on manipulating the assembly of the viral coat proteins. Herein, we report a new assembly system based on a triblock polypolypeptide C4-S10-BK12 and -COONa terminated PAMAM dendrimers. The polypolypeptide has a cationic BK12 block with 12 lysines; its binding with anionic PAMAM triggers the folding of the peptide's middle silk-like block and leads to formation of virus-like nanorods, stabilized against aggregation by the long hydrophilic "C" block of the polypeptide. Varying the dendrimer/polypeptide mixing ratio hardly influences the structure and size of the nanorod. However, increasing the dendrimer generation, that is, increasing the dendrimer size results in increased particle length and height, without affecting the width of the nanorod. The branched structure and well-defined size of the dendrimers allows delicate control of the particle size; it is impossible to achieve similar control over assembly of the polypeptide with linear polyelectrolyte as template. In conclusion, we report a novel protein assembling system with properties resembling a viral coat; the findings may therefore be helpful for designing functional virus-like particles like vaccines.

Necrotic Ulceration of the Hand Case Review: Think Beyond Infection.

Neutrophilic dermatosis of the dorsal hands is a rare neutrophilic dermatosis that can be associated with inflammatory bowel disease, rheumatoid arthritis, and underlying malignancies. The occurrence of trauma as an initiating factor and its early features of pain and inflammation followed by blistering or ulceration mean that it can be mistaken for necrotizing infection. Neutrophilic dermatosis of the dorsal hands should be considered in all patients who present with such features confined to the back of the hands, particularly those with negative microbiological results or lack of response to antibiotic therapy. A case review design was used to analyze the presentation of a woman aged 65 years in the United Kingdom, seeking care for a painful rash on the hand in the emergency department that was subsequently diagnosed as neutrophilic dermatosis of the dorsal hands. Emergency clinician awareness of neutrophilic dermatosis of the dorsal hands as a rare differential diagnosis for patients presenting with necrotic ulceration may prevent unnecessary antibiotic therapy and surgical intervention.

Sex Differences in Coronary Arterial Calcification in Symptomatic Patients.

Despite the increasing use of Coronary Artery Calcium (CAC) scoring for cardiovascular risk stratification in asymptomatic patients, the gender differences in CAC among symptomatic patients have not been well evaluated. We analyzed patients presenting to the emergency department (ED) with chest pain suggesting possible coronary artery disease (CAD) who received coronary computed tomography angiography (CCTA). Ordinal logistic regression was used to determine the odds ratio for the association of traditional cardiovascular risk factors and CAC. Patients with a CAC score ≥ 100 were followed for cardiovascular events or changes in medical management. Our cohort included 542 individuals (263 male, 279 female). Ordinal logistic regression model showed that among traditional cardiovascular risk factors, male sex had the highest odds ratio (OR) of 3.04 (p < 0.001, 95% CI [2.01, 4.59]) for the presence of CAC. Also, males had more diffuse distribution of coronary atherosclerosis (p=0.01). Subgroup analysis revealed that obesity was a bigger risk factor in male patients (OR 2.16), while smoking showed the greatest effect (OR 4.27) on CAC in women. Of patients who had CAC > 100 with an average follow-up of 346 days, there was an increase in both aspirin and statin use, yet significant sex differences were observed especially in patients with non-obstructive lesions on CCTA. Among male patients with non-obstructive lesions, 68.2% were on aspirin and 86.4% were on statin therapy after the CCTA compared to 27.3% and 45.5% respectively in their female counterparts. In conclusion, sex not only is the most powerful predictor for higher CAC among traditional cardiovascular risk factors in symptomatic patients but also influences the contribution of various traditional risk factors to elevated CAC. Furthermore, the discovery of CAD led to the initiation of medical therapy in male patients more frequently than in female patients, even after adjusting for the degree of luminal stenosis detected on coronary CT angiography.

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

A Community-transmitted Case of Severe Acute Respiratory Distress Syndrome (SARS) Due to SARS-CoV-2 in the United States.

This is the first known community transmission case of the novel coronavirus disease (COVID-19) in the United States, with significant public health implications. Diagnosis of COVID-19 is currently confirmed with PCR based testing of appropriate respiratory samples. Given the absence of travel or known exposure history, this patient did not meet the criteria for testing according to CDC guidelines at the time of her presentation. Since this case, any patient with severe disease (eg, ARDS or pneumonia) requiring hospitalization without an explanatory diagnosis can be tested even if no clear source of exposure is identified. While influencing national health policies for revising screening criteria, this case also highlighted significant knowledge gaps in diagnosis and treatment and a desperate need for early, widespread, fast and cheap testing for COVID-19.