Takotsubo syndrome has been reported in patients with COVID-19, although minimal data are available. This investigation assessed the incidence and impact of takotsubo syndrome on patients ...hospitalized with COVID-19.
A retrospective cohort study was conducted using International Statistical Classification of Diseases, Tenth Revision, codes to identify patients with a primary diagnosis of COVID-19 with or without takotsubo syndrome in the National Inpatient Sample 2020 database. Outcomes between groups were compared after propensity score matching for patient and hospital demographics and comorbidities.
A total of 211,448 patients with a primary diagnosis of COVID-19 were identified. Of these, 171 (0.08%) had a secondary diagnosis of takotsubo syndrome. Before matching, patients with COVID-19 and takotsubo syndrome, compared with patients without takotsubo syndrome, were older (68.95 vs 64.26 years; P < .001); more likely to be female (64.3% vs 47.2%; P < .001); and more likely to have anxiety (24.6% vs 12.8%; P < .001), depression (17.5% vs 11.4%; P = .02), and chronic obstructive pulmonary disease (24.6% vs 14.7%; P < .001). The takotsubo syndrome group had worse outcomes than the non-takotsubo syndrome group for death (30.4% vs 11.1%), cardiac arrest (7.6% vs 2.1%), cardiogenic shock (12.9% vs 0.4%), length of hospital stay (10.7 vs 7.5 days), and total charges ($152,685 vs $78,468) (all P < .001). After matching and compared with the non-takotsubo syndrome group (n = 508), the takotsubo syndrome group (n = 170) had a higher incidence of inpatient mortality (30% vs 14%; P < .001), cardiac arrest (7.6% vs 2.8%; P = .009), and cardiogenic shock (12.4% vs 0.4%; P < .001); a longer hospital stay (10.7 vs 7.6 days; P < .001); and higher total charges ($152,943 vs $79,523; P < .001).
Takotsubo syndrome is a rare but severe in-hospital complication in patients with COVID-19.
Summary Background Antiretroviral regimens containing tenofovir disoproxil fumarate have been associated with renal toxicity and reduced bone mineral density. Tenofovir alafenamide is a novel ...tenofovir prodrug that reduces tenofovir plasma concentrations by 90%, thereby decreasing off-target side-effects. We aimed to assess whether efficacy, safety, and tolerability were non-inferior in patients switched to a regimen containing tenofovir alafenamide versus in those remaining on one containing tenofovir disoproxil fumarate. Methods In this randomised, actively controlled, multicentre, open-label, non-inferiority trial, we recruited HIV-1-infected adults from Gilead clinical studies at 168 sites in 19 countries. Patients were virologically suppressed (HIV-1 RNA <50 copies per mL) with an estimated glomerular filtration rate of 50 mL per min or greater, and were taking one of four tenofovir disoproxil fumarate-containing regimens for at least 96 weeks before enrolment. With use of a third-party computer-generated sequence, patients were randomly assigned (2:1) to receive a once-a-day single-tablet containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (tenofovir alafenamide group) or to carry on taking one of four previous tenofovir disoproxil fumarate-containing regimens (tenofovir disoproxil fumarate group) for 96 weeks. Randomisation was stratified by previous treatment regimen in blocks of six. Patients and treating physicians were not masked to the assigned study regimen; outcome assessors were masked until database lock. The primary endpoint was the proportion of patients who received at least one dose of study drug who had undetectable viral load (HIV-1 RNA <50 copies per mL) at week 48. The non-inferiority margin was 12%. This study was registered with ClinicalTrials.gov , number NCT01815736. Findings Between April 12, 2013 and April 3, 2014, we enrolled 1443 patients. 959 patients were randomly assigned to the tenofovir alafenamide group and 477 to the tenofovir disoproxil fumarate group. Viral suppression at week 48 was noted in 932 (97%) patients assigned to the tenofovir alafenamide group and in 444 (93%) assigned to the tenofovir disoproxil fumarate group (adjusted difference 4·1%, 95% CI 1·6–6·7), with virological failure noted in ten and six patients, respectively. The number of adverse events was similar between the two groups, but study drug-related adverse events were more common in the tenofovir alafenamide group (204 patients 21% vs 76 16%). Hip and spine bone mineral density and glomerular filtration were each significantly improved in patients in the tenofovir alafenamide group compared with those in the tenofovir disoproxil fumarate group. Interpretation Switching to a tenofovir alafenamide-containing regimen from one containing tenofovir disoproxil fumarate was non-inferior for maintenance of viral suppression and led to improved bone mineral density and renal function. Longer term follow-up is needed to better understand the clinical impact of these changes. Funding Gilead Sciences.
Summary Background NSABP B-40 was a 3 × 2 factorial trial testing whether adding capecitabine or gemcitabine to docetaxel followed by doxorubicin plus cyclophosphamide neoadjuvant chemotherapy would ...improve outcomes in women with operable, HER2-negative breast cancer and whether adding neoadjuvant plus adjuvant bevacizumab to neoadjuvant chemotherapy regimens would also improve outcomes. As reported previously, addition of neoadjuvant bevacizumab increased the proportion of patients achieving a pathological complete response, which was the primary endpoint. We present secondary patient outcomes, including disease-free survival, a specified endpoint by protocol, and data for distant recurrence-free interval, and overall survival, which were not prespecified endpoints but were collected prospectively. Methods In this randomised controlled trial (NSABP B-40), we enrolled women aged 18 years or older, with operable, HER2-non-amplified invasive adenocarcinoma of the breast, 2 cm or greater in diameter by palpation, clinical stage T1c–3, cN0, cN1, or cN2a, without metastatic disease and diagnosed by core needle biopsy. Patients received one of three docetaxel-based neoadjuvant regimens for four cycles: docetaxel alone (100 mg/m2 ) with addition of capecitabine (825 mg/m2 oral twice daily days 1–14, 75 mg/m2 docetaxel) or with addition of gemcitabine (1000 mg/m2 days 1 and 8 intravenously, 75 mg/m2 docetaxel), all followed by neoadjuvant doxorubicin and cyclophosphamide (60 mg/m2 and 600 mg/m2 intravenously) every 3 weeks for four cycles. Those randomly assigned to bevacizumab groups were to receive bevacizumab (15 mg/kg, every 3 weeks for six cycles) with neoadjuvant chemotherapy and postoperatively for ten doses. Randomisation was done (1:1:1:1:1:1) via a biased-coin minimisation procedure to balance the characteristics with respect to clinical nodal status, clinical tumour size, hormone receptor status, and age. Intent-to-treat analyses were done for disease-free survival and overall survival. This study is registered with ClinicalTrials.gov , number NCT00408408. Findings Between Jan 5, 2007, and June 30, 2010, 1206 patients were enrolled in the study. Follow-up data were collected from Oct 31, 2007 to March 27, 2014, and were available for overall survival in 1186 patients, disease-free survival in 1184, and distant recurrence-free interval in 1181. Neither capecitabine nor gemcitabine increased disease-free survival or overall survival. Median follow-up was 4·7 years (IQR 4·0–5·2). The addition of bevacizumab significantly increased overall survival (hazard ratio 0·65 95% CI 0·49–0·88; p=0·004) but did not significantly increase disease-free survival (0·80 0·63–1·01; p=0·06). Four deaths occurred on treatment due to vascular disorder (docetaxel plus capecitabine followed by doxorubicin plus cyclophosphamide group), sudden death (docetaxel plus capecitabine followed by doxorubicin plus cyclophosphamide group), infective endocarditis (docetaxel plus bevacizumab followed by doxorubicin plus cyclophosphamide and bevacizumab group), and visceral arterial ischaemia (docetaxel followed by doxorubicin plus cyclophosphamide group). The most common grade 3–4 adverse events in the bevacizumab group were neutropenia (grade 3, 99 17%; grade 4, 37 6%), hand-foot syndrome (grade 3, 63 11%), and hypertension (grade 3, 60 10%; grade 4, two <1%) and in the non-bevacizumab group were neutropenia (grade 3, 98 16%; grade 4, 36 6%), fatigue (grade 3, 53 9%), and hand-foot syndrome (grade 3, 43 7%). Interpretation The addition of gemcitabine or capecitabine to neoadjuvant docetaxel plus doxorubicin plus cyclophosphamide does not seem to provide any benefit to patients with operable breast cancer, and should not change clinical practice in the short term. The improved overall survival with bevacizumab contradicts the findings of other studies of bevacizumab in breast cancer and may indicate the need for additional investigation of this agent. Funding National Institutes of Health, Genentech, Roche Laboratories, Lilly Research Laboratories, and Precision Therapeutics.
OBJECTIVES:
Treatments that prevent sepsis complications are needed. Circulating lipid and protein assemblies—lipoproteins play critical roles in clearing pathogens from the bloodstream. We ...investigated whether early inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) may accelerate bloodstream clearance of immunogenic bacterial lipids and improve sepsis outcomes.
DESIGN:
Genetic and clinical epidemiology, and experimental models.
SETTING:
Human genetics cohorts, secondary analysis of a phase 3 randomized clinical trial enrolling patients with cardiovascular disease (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab ODYSSEY OUTCOMES; NCT01663402), and experimental murine models of sepsis.
PATIENTS OR SUBJECTS:
Nine human cohorts with sepsis (total
n
= 12,514) were assessed for an association between sepsis mortality and
PCSK9
loss-of-function (LOF) variants. Incident or fatal sepsis rates were evaluated among 18,884 participants in a post hoc analysis of ODYSSEY OUTCOMES. C57BI/6J mice were used in
Pseudomonas aeruginosa
and
Staphylococcus aureus
bacteremia sepsis models, and in lipopolysaccharide-induced animal models.
INTERVENTIONS:
Observational human cohort studies used genetic
PCSK9
LOF variants as instrumental variables. ODYSSEY OUTCOMES participants were randomized to alirocumab or placebo. Mice were administered alirocumab, a PCSK9 inhibitor, at 5 mg/kg or 25 mg/kg subcutaneously, or isotype-matched control, 48 hours prior to the induction of bacterial sepsis. Mice did not receive other treatments for sepsis.
MEASUREMENTS AND MAIN RESULTS:
Across human cohort studies, the effect estimate for 28-day mortality after sepsis diagnosis associated with genetic
PCSK9
LOF was odds ratio = 0.86 (95% CI, 0.67–1.10;
p
= 0.24). A significant association was present in antibiotic-treated patients. In ODYSSEY OUTCOMES, sepsis frequency and mortality were infrequent and did not significantly differ by group, although both were numerically lower with alirocumab vs. placebo (relative risk of death from sepsis for alirocumab vs. placebo, 0.62; 95% CI, 0.32–1.20;
p
= 0.15). Mice treated with alirocumab had lower endotoxin levels and improved survival.
CONCLUSIONS:
PCSK9 inhibition may improve clinical outcomes in sepsis in preventive, pretreatment settings.
Abstract Background Lung cancer has been the leading cause of cancer death in China since the 1990s, and the disease burden is predicted to increase. The US National Lung Screening Trial (NLST) ...showed that annual low-dose CT resulted in a 15–20% mortality reduction in high-risk populations compared with chest x-ray, and the China National Cancer Center would like to confirm this finding in the Chinese population. Additionally, China has not yet developed national guidelines for lung and colorectal cancer screening, and scientific evidence from the Chinese population is needed to inform policy making. The China Cancer Screening Trial Feasibility Study seeks to obtain information necessary to design a long-term randomised lung and colorectal cancer screening trial. The primary objectives are to develop and test all data forms and data collection procedures; to assess the feasibility of recruitment and randomisation of participants into study arms, and the success of randomisation by comparing the distribution of baseline variables across arms, contamination in each arm, and compliance with screening exams and diagnostic follow-up after positive screening in each arm; to determine the positivity rates at each screening round in each arm; to identify and collect data for cancers in each arm over the study period; to develop and test procedures that collect and store biological samples; and to assess the performance of the organisations involved in designing, conducting, monitoring, and managing the study. Methods The study has been set up in three cites (Changsha, Hunan province; Lanzhou, Gansu province; and Haining, Zhejiang province) since August, 2014. Individuals at elevated risk of lung cancer were randomised into three arms: annual low-dose helical CT exams for 3 years (T0, T1, T2) and baseline colonoscopy (T0); two low-dose helical CT exams (T0, T2) plus annual faecal immunochemical test (OC-faecal immunochemical tests at T0, T1, T2); and annual InSure-faecal immunochemical tests combined with Septin 9 test (T0, T1, T2). A randomly selected 6 or 9 block size was used for randomisation. Staff at screening centres and all the participants were blinded to the order of randomisation, and enrolment was done by each screening centre. All participants will be followed for at least 3 years from randomisation to yield data stated in the study objectives. This study was approved by the ethics committee of Cancer Hospital, Chinese Academy of Medical Science, in June, 2014 (14-058/848). All participants signed informed consent forms before recruitment. Findings As of March 31, 2015, 2700 eligible participants, 900 in each study centre, were randomised into the three arms. Participants were stratified on the basis of sex and age (50–54 years, 55–59 years, 60–64 years, 65–69 years, and 70–74 years) in each centre. Low-dose spiral CT abnormality and non-calcified nodule/mass distribution were assessed. In each arm, compliance with the screening exams, positivity rates at the baseline screening, and compliance with diagnostic follow-up after positive screening exams were also studied. Interpretation This is the first randomised trial of lung and colorectal cancer screening in China. Results from the Feasibility Study will help to develop a practical design for the Randomised Cancer Screening Trial in China. Funding Cancer Institute and Hospital, Chinese Academy of Medical Sciences, and The National Health and Family Plan Committee of China.
Background The cause of corticosteroid-resistant (CR) asthma is unknown. Objective We sought to perform gene microarray analyses by using bronchoalveolar lavage (BAL) cells from well-characterized ...subjects with CR asthma and subject with corticosteroid-sensitive (CS) asthma to elucidate the differential expression of genes that contribute to the development of corticosteroid resistance. Methods The patients were characterized as having CR or CS asthma based on FEV1 percent predicted improvement after a 1-week course of oral prednisone. Expression of selected gene targets was verified by means of real-time PCR and ELISA. Results Microarray analyses demonstrated significantly higher levels (>3-fold increase, P < .05) of transcripts for TNF-α, IL-1α, IL-1β, IL-6, CXCL1, CXCL2, CXCL3, CXCL8 (IL-8), CCL3, CCL4, and CCL20 in BAL cells of subjects with CR asthma. These findings, confirmed by means of RT-PCR in additional BAL samples, were consistent with classical macrophage activation by bacterial products. In contrast, markers of alternatively activated macrophages, arginase I and CCL24, were decreased. Genes associated with activation of the LPS signaling pathway (early growth response 1, dual-specificity phosphatase 2, molecule possessing ankyrin repeats induced by LPS, and TNF-α–induced protein 3) were significantly increased in BAL samples from subjects with CR asthma ( P < .05). These patients had significantly higher amounts (1444.0 ± 457.3 pg/mg total protein) of LPS in BAL fluid than seen in subjects with CS asthma (270.5 ± 216.0 pg, P < .05), as detected by using the LAL assay and confirmed by means of gas chromatographic/mass spectrometric analysis. Prolonged exposure to LPS induced functional steroid resistance to dexamethasone in normal human monocytes, as demonstrated by persistently increased IL-6 levels in the presence of dexamethasone. Conclusions Classical macrophage activation and induction of LPS signaling pathways along with high endotoxin levels detected in BAL fluid from subjects with CR asthma suggest that LPS exposure might contribute to CR asthma.
Interest and application of stereotactic radiosurgery for multiple brain metastases continue to increase. Various planning systems are available for linear accelerator (linac)–based single-isocenter ...multiple metastasis radiosurgery. Two of the most advanced systems are BrainLAB Multiple Metastases Elements (MME), a dynamic conformal arc (DCA) approach, and Varian RapidArc (RA), a volumetric modulated arc therapy (VMAT) approach. In this work, we systematically compared plan quality between the 2 techniques.
Thirty patients with 4 to 10 metastases (217 total; median 7.5; Vmin = 0.014 cm3; Vmax = 17.73 cm3) were planned with both Varian RA and MME at 2 different institutions with extensive experience in each respective technique. All plans had a single isocenter and used Varian linac equipped with high-definition multileaf collimator. RA plans used 2 to 4 noncoplanar VMAT arcs with 10 MV flattening filter-free beam. MME plans used 4 to 9 noncoplanar DCAs and 6 MV flattening filter-free beam, (minimum planning target volume PTVmin = 0.49 cm3; PTVmax = 27.32 cm3; PTVmedian = 7.05 cm3). Prescriptions were 14 to 24 Gy in a single fraction. Target coverage goal was 99% of volume receiving prescription dose (D99% ≥ 100%). Plans were evaluated by Radiation Therapy Oncology Group/Paddick conformity index (CI) score, 12 Gy volume (V12Gy), V8Gy, V5Gy, mean brain dose (Dmean), and beam-on time.
Conformity was favorable among RA plans (median: MME CIRTOG = 1.38; RA CIRTOG = 1.21; P < .0001). V12Gy and V8Gy were lower for RA plans (median: MME V12 = 23.7 cm3; RA V12 = 19.2 cm3; P = .0001; median: MME V8Gy = 53.6 cm3; RA V8Gy = 44.1 cm3; P = .024). V5Gy was lower for MME plans (median: MME V5Gy = 141.4 cm3; RA V5Gy = 142.8 cm3; P = .009). Mean brain was lower for MME plans (median: MME Dmean = 2.57 Gy; RA Dmean = 2.76 Gy; P < .0001).
For linac-based multiple metastasis stereotactic radiosurgery, RapidArc VMAT facilitates favorable conformity and V12Gy/V8Gy volume compared with the MME DCA plan. MME planning facilitates reduced dose spill at levels ≤V5Gy.
Abstract The concepts of “cardiometabolic risk,” “metabolic syndrome,” and “risk stratification” overlap and relate to the atherogenic process and development of type 2 diabetes. There is confusion ...about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. With the objectives of clarifying these concepts and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group reviewed the evidence related to emerging cardiovascular risk factors and Canadian guideline recommendations in order to present a detailed analysis and consolidated approach to the identification and management of cardiometabolic risk. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. “Global cardiometabolic risk” is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider risk factors related to ethnicity in order to appropriately evaluate everyone in their diverse patient populations.
Background Noninvasive sputum sampling has enabled the identification of biomarkers in asthmatic patients. Studies of discrete cell populations in sputum can enhance measurements compared with whole ...sputum in which changes in rare cells and cell-cell interactions can be masked. Objective We sought to enrich for sputum-derived human bronchial epithelial cells (sHBECs) and sputum-derived myeloid type 1 dendritic cells (sDCs) to describe transcriptional coexpression of targets associated with a type 2 immune response. Methods A case-control study was conducted with patients with mild asthma (asthmatic cases) and healthy control subjects. Induced sputum was obtained for simultaneous enrichment of sHBECs and sDCs by using flow cytometry. Quantitative PCR was used to measure mRNA for sHBEC thymic stromal lymphopoietin (TSLP) , IL33 , POSTN , and IL25 and downstream targets in sDCs (OX40 ligand OX40L , CCL17 , PPP1R14A , CD1E , CD1b , CD80 , and CD86 ). Results Final analyses for the study sample were based on 11 control subjects and 13 asthmatic cases. Expression of TSLP , IL33 , and POSTN mRNA was increased in sHBECs in asthmatic cases ( P = .001, P = .05, and P = .04, respectively). Expression of sDC OX40L and CCL17 mRNA was increased in asthmatic cases ( P = .003 and P = .0001, respectively). sHBEC TSLP mRNA expression was strongly associated with sDC OX40L mRNA expression ( R = 0.65, P = .001) and less strongly with sDC CCL17 mRNA expression. sHBEC IL33 mRNA expression was associated with sDC OX40L mRNA expression ( R = 0.42, P = .04) but not sDC CCL17 mRNA expression. Conclusions Noninvasive sampling and enrichment of select cell populations from sputum can further our understanding of cell-cell interactions in asthmatic patients with the potential to enhance endotyping of asthmatic patients.
PDF
