Background and objectives

Oxidative stress is a hallmark and mediator of CKD. Diminished antioxidant defenses are thought to be partly responsible. However, there is currently no way to prospectively assess antioxidant defenses in humans. Tin protoporphyrin (SnPP) induces mild, transient oxidant stress in mice, triggering increased expression of select antioxidant proteins (e.g., heme oxygenase 1 [HO-1], NAD[P]H dehydrogenase [quinone] 1 [NQO1], ferritin, p21). Hence, we tested the hypothesis that SnPP can also variably increase these proteins in humans and can thus serve as a pharmacologic "stress test" for gauging gene responsiveness and antioxidant reserves.

Background and objectives

Large, randomized, controlled trials targeting higher hemoglobin level with erythropoiesis-stimulating agents for Western patients with CKD showed harm. However, the effect of anemia correction using erythropoiesis-stimulating agents may differ between CKD subpopulations. The Prevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease study, a multicenter, randomized, open-label, parallel-group study, aimed to examine the effect of targeting hemoglobin levels of 11–13 g/dl using darbepoetin alfa with reference to a low-hemoglobin target of 9–11 g/dl on kidney outcome in patients with advanced CKD without diabetes in Japan.

Background and objectives

This study aimed to investigate the association between in-hospital trajectories of serum sodium and risk of in-hospital and 1-year mortality in patients in hospital.

The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in patients with metastatic pancreatic cancer who were enrolled in two phase II randomized studies of GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used to simultaneously measure 38 cell surface or intracellular markers in peripheral blood mononuclear cells obtained from a phase IIa patient subcohort (N = 38). CITRUS, an algorithm for identification of stratifying subpopulations in multidimensional cytometry datasets, was used to identify single-cell signatures associated with clinical outcome. Patients with a higher abundance of CD8⁺CD45RO^–CCR7^–CD57⁺ cells and a lower abundance of CD14⁺CD33⁺CD85j⁺ cells had improved overall survival [median overall survival, range (days) 271, 43–1,247] compared with patients with a lower abundance of CD8⁺CD45RO^–CCR7^–CD57⁺ cells and higher abundance of CD14⁺CD33⁺CD85j⁺ cells (77, 24–1,247 days; P = 0.0442). The results from this prospective–retrospective biomarker analysis were validated by flow cytometry in 200 patients with pancreatic cancer enrolled in a phase IIb study (P = 0.0047). The identified immune correlates provide potential prognostic or predictive signatures that could be employed for patient stratification.

We conducted a 7-year case–control study of people ≥30 years of age on the prevalence of influenza, gastroenteritis, hepatitis, and pneumonia infections to indirectly examine whether these infections correlated to malignant cancer formation. Data were extracted from a large medical claims database of a Japanese social health insurance system; the case group included 2,354 people with their first cancer diagnosis in the 7th year of this study, and the control group included 48,395 people with no cancer diagnosis by the 7th year. The yearly prevalence rates of influenza, gastroenteritis, hepatitis, and pneumonia infections increased throughout the study period. Age-adjusted ORs and 95% confidence intervals (CI) in cases 1 year before cancer detection were significantly higher—for influenza 1.29 (95% CI, 1.14–1.46), for gastroenteritis 1.60 (95% CI, 1.41–1.82), for hepatitis 3.38 (95% CI, 2.12–5.37), for pneumonia 2.36 (95% CI, 1.79–3.13), and for any of these four diseases 1.55 (95% CI, 1.40–1.70). In influenza infections, significant ORs were found only in the 2nd and 6th years before cancer diagnosis. For each cancer site, an increased rate of infection prior to cancer diagnosis was observed. Here, we showed that increased infections during the precancerous stage, a possible surrogate for tumor-induced immune suppression, correlated to eventual cancer development.

Background:

Incentive payments for chronic diseases in British Columbia were intended to support primary care physicians in providing more comprehensive care, but research shows that not all physicians bill incentives and not all eligible patients have them billed on their behalf. We investigated patient and physician characteristics associated with billing incentives for chronic diseases in BC.

Background:

Care services have not been sufficiently adapted to meet the comprehensive care needs of women living with HIV. Our study objective was to engage patients and providers in codesigning care recommendations to improve care for this population in the province of Quebec.

Background:

Patients with multimorbidity often require services across different health care settings, yet team processes among settings are rarely implemented. We explored perceptions of specialists and family physicians collaborating in a telemedicine interprofessional consultation for patients with multimorbidity to better understand the value of bringing physicians together across the boundaries of health care settings.

Hyponatremiahyposmolarreset osmostatsyndrome of inappropriate antidiuresiselderly

Lai et al. report the case of an elderly gentleman who presented with resolving neurologic findings from a transient ischemic attack and who was found to have hyponatremia with a serum sodium concentration of 123 mmol/L. Hypoosmolality was confirmed, and a diluting defect identified with a urine osmolality that ranged between 167 and 285 mOsm/kg. As the urine osmolality rose to > 400 mOsm/kg with water deprivation, a diagnosis of syndrome of inappropriate antidiuresis (SIAD) from reset osmostat was entertained.

Hyponatremia, the most common electrolyte disorder, is present in 2%–4% of ambulatory patients and up to 22% of geriatric inpatients (1). Clinicians classify hyponatremia into three main categories: hypovolemic (decreased intravascular volume from salt and water loss with inadequate replacement), euvolemic (normal intravascular volume, but increased water dilutes sodium), and hypervolemic (total body water is increased, usually causing edema, while intravascular volume is often decreased). Less frequent causes are pseudohyponatremia (due to decreased water in a fixed volume of plasma, usually due to increased lipids or protein) and water shifting due to increased osmolality (most commonly due to glucose). While the most extreme examples of hypovolemic and hypervolemic states can be determined by physical examination, in many cases the patient is euvolemic clinically.

Chronic obstructive pulmonary disease (COPD) is characterised by persistent respiratory symptoms and airflow limitation, which is caused by small airway disease (bronchiolitis) and alveolar destruction (emphysema) [1]. Patients primarily suffering from severe emphysema are often limited in exercise capacity due to the consequences of hyperinflation [2].

The diagnostic process of idiopathic interstitial pneumonias (IIPs) is complex and the underlying mechanisms that participate in these diseases still need to be fully understood. In 2015, the European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-Associated Interstitial Lung Disease introduced the term "interstitial pneumonia with autoimmune features" (IPAF) to identify subjects with IIP and features suggesting background autoimmunity but not characterisable connective tissue disease (CTD) [1]. The need for a proper clinical, serological and morphological assessment of IIP was highlighted to identify potential subjects with IPAF and CTD-ILD. However, the measurement of anti-neutrophil cytoplasmic antibodies (ANCAs) is not included in the definition of IPAF and ANCA serological testing is only recommended in idiopathic pulmonary fibrosis (IPF) when a clinical suspicion of vasculitis exists [2]. As current research evaluates the prognostic relevance of autoimmune features in IIP, the clinical importance of ANCA positivity still needs to be determined.

Purpose:

Unleashing the immune system by PD-1 and/or CTLA-4 blockade can cause severe immune-related toxicity necessitating immunosuppressive treatment. Whether immunosuppression for toxicity impacts survival is largely unknown.

Purpose:

The development of leptomeningeal melanoma metastases (LMM) is a rare and devastating complication of the late-stage disease, for which no effective treatments exist. Here, we performed a multi-omics analysis of the cerebrospinal fluid (CSF) from patients with LMM to determine how the leptomeningeal microenvironment shapes the biology and therapeutic responses of melanoma cells.

Purpose:

Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both in vitro and in patients with ABC.

Purpose:

Preclinical data demonstrating androgen receptor (AR)–positive (AR⁺) triple-negative breast cancer (TNBC) cells are sensitive to AR antagonists, and PI3K inhibition catalyzed an investigator-initiated, multi-institutional phase Ib/II study TBCRC032. The trial investigated the safety and efficacy of the AR-antagonist enzalutamide alone or in combination with the PI3K inhibitor taselisib in patients with metastatic AR⁺ (≥10%) breast cancer.

Purpose:

In the phase III DUO trial, duvelisib, an oral dual PI3K-, inhibitor, demonstrated significantly improved efficacy versus ofatumumab [median (m) progression-free survival (PFS), 13.3 vs. 9.9 months (HR, 0.52; P < 0.0001); overall response rate [ORR], 74% vs. 45% (P < 0.0001)], with a manageable safety profile in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). We report results from patients with progressive disease (PD) after ofatumumab who crossed over to duvelisib in the DUO trial.

Nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP), is increasingly associated with multidrug-resistant Gram-negative pathogens. This study describes the in vitro activity of ceftazidime-avibactam, ceftazidime, and relevant comparator agents against bacterial pathogens isolated from patients with NP, including VAP, enrolled in a ceftazidime-avibactam phase 3 trial. Gram-positive pathogens were included if coisolated with a Gram-negative pathogen. In vitro susceptibility was determined at a central laboratory using Clinical and Laboratory Standards Institute broth microdilution methods. Of 817 randomized patients, 457 (55.9%) had ≥1 Gram-negative bacterial pathogen(s) isolated at baseline, and 149 (18.2%) had ≥1 Gram-positive pathogen(s) coisolated. The most common isolated pathogens were Klebsiella pneumoniae (18.8%), Pseudomonas aeruginosa (15.8%), and Staphylococcus aureus (11.5%). Ceftazidime-avibactam was highly active in vitro against 370 isolates of Enterobacteriaceae, with 98.6% susceptible (MIC₉₀, 0.5 μg/ml) compared with 73.2% susceptible for ceftazidime (MIC₉₀, >64 μg/ml). The percent susceptibility values for ceftazidime-avibactam and ceftazidime against 129 P. aeruginosa isolates were 88.4% and 72.9% (MIC₉₀ values of 16 μg/ml and 64 μg/ml), respectively. Among ceftazidime-nonsusceptible Gram-negative isolates, ceftazidime-avibactam percent susceptibility values were 94.9% for 99 Enterobacteriaceae and 60.0% for 35 P. aeruginosa. MIC₉₀ values for linezolid and vancomycin (permitted per protocol for Gram-positive coverage) were within their respective MIC susceptibility breakpoints against the Gram-positive pathogens isolated. This analysis demonstrates that ceftazidime-avibactam was active in vitro against the majority of Enterobacteriaceae and P. aeruginosa isolates from patients with NP, including VAP, in a phase 3 trial. (This study has been registered at ClinicalTrials.gov under identifier NCT01808092.)

The RESTORE-IMI 1 phase 3 trial demonstrated the efficacy and safety of imipenem-cilastatin (IMI) combined with relebactam (REL) for treating imipenem-nonsusceptible infections. The objective of this analysis was to compare the outcomes among patients meeting eligibility requirements based on central laboratory susceptibility versus local laboratory susceptibility. Patients with serious infections caused by imipenem-nonsusceptible, colistin-susceptible, and imipenem-REL-susceptible pathogens were randomized 2:1 to IMI-REL plus placebo or colistin plus IMI for 5 to 21 days. The primary endpoint was a favorable overall response. Key endpoints included the clinical response and all-cause mortality. We compared outcomes between the primary microbiological modified intent-to-treat (mMITT) population, where eligibility was based on central laboratory susceptibility testing, and the supplemental mMITT (SmMITT) population, where eligibility was based on local, site-level testing. The SmMITT (n = 41) and MITT (n = 31) populations had similar baseline characteristics, including sex, age, illness severity, and renal function. In both analysis populations, favorable overall response rates in the IMI-REL treatment group were >70%. Favorable clinical response rates at day 28 were 71.4% for IMI-REL and 40.0% for colistin plus IMI in the mMITT population, whereas they were 75.0% for IMI-REL and 53.8% for colistin plus IMI in the SmMITT population. Day 28 all-cause mortality rates were 9.5% for IMI-REL and 30.0% for colistin plus IMI in the mMITT population, whereas they were 10.7% for IMI-REL and 23.1% for colistin plus IMI in the SmMITT population. The outcomes in the SmMITT population were generally consistent with those in the mMITT population, suggesting that outcomes may be applicable to the real-world use of IMI-REL for treating infections caused by imipenem-nonsusceptible Gram-negative pathogens. (This study has been registered at ClinicalTrials.gov under identifier NCT02452047.)

The aim of this work was to evaluate the pharmacokinetics of amikacin in Mexican patients with different renal functions receiving once-daily dosing regimens and the influence of clinical and demographical covariates that may influence the optimization of this antibiotic. A prospective study was performed in a total of 63 patients with at least one determination of amikacin plasma concentration. Population pharmacokinetic (PK) parameters were estimated by nonlinear mixed-effects modeling; validations were performed for dosing recommendation purposes based on PK/pharmacodynamic simulations. The concentration-versus-time data were best described by a one-compartment open model with proportional interindividual variability associated with amikacin clearance (CL) and volume of distribution (V); residual error followed a homoscedastic trend. Creatinine clearance (CL_CR) and ideal body weight (IBW) demonstrated significant influence on amikacin CL and V, respectively. The final model [CL (liters/h) = 7.1 x (CL_CR/130)^0.84 and V (liters) = 20.3 x (IBW/68)^2.9] showed a mean prediction error of 0.11 mg/liter (95% confidence interval, –3.34, 3.55) in the validation performed in a different group of patients with similar characteristics. There is a wide variability in amikacin PK parameters in Mexican patients. This leads to inadequate dosing regimens, especially in patients with augmented renal clearance (CL_CR of >130 ml/min). Optimization based on the final population PK model in Mexican patients may be useful, since reliability and clinical applicability have been demonstrated in this study.

Pseudomonas aeruginosa exploits intrinsic and acquired resistance mechanisms to resist almost every antibiotic used in chemotherapy. Antimicrobial resistance in P. aeruginosa isolates recovered from cystic fibrosis (CF) patients is further enhanced by the occurrence of hypermutator strains, a hallmark of chronic infections in CF patients. However, the within-patient genetic diversity of P. aeruginosa populations related to antibiotic resistance remains unexplored. Here, we show the evolution of the mutational resistome profile of a P. aeruginosa hypermutator lineage by performing longitudinal and transversal analyses of isolates collected from a CF patient throughout 20 years of chronic infection. Our results show the accumulation of thousands of mutations, with an overall evolutionary history characterized by purifying selection. However, mutations in antibiotic resistance genes appear to have been positively selected, driven by antibiotic treatment. Antibiotic resistance increased as infection progressed toward the establishment of a population constituted by genotypically diversified coexisting sublineages, all of which converged to multidrug resistance. These sublineages emerged by parallel evolution through distinct evolutionary pathways, which affected genes of the same functional categories. Interestingly, ampC and ftsI, encoding the β-lactamase and penicillin-binding protein 3, respectively, were found to be among the most frequently mutated genes. In fact, both genes were targeted by multiple independent mutational events, which led to a wide diversity of coexisting alleles underlying β-lactam resistance. Our findings indicate that hypermutators, apart from boosting antibiotic resistance evolution by simultaneously targeting several genes, favor the emergence of adaptive innovative alleles by clustering beneficial/compensatory mutations in the same gene, hence expanding P. aeruginosa strategies for persistence.

Dalbavancin offers a possible treatment option for infectious peritonitis associated with peritoneal dialysis (PD) due to its coverage of Gram-positive bacteria and pharmacokinetic properties. We aimed to evaluate the clinical pharmacokinetics (PK) and pharmacodynamics of dalbavancin in a prospective, randomized, open-label, crossover PK study of adult patients with end-stage renal disease ESRD who were receiving PD. Sampling occurred prior to a single 30-min infusion of dalbavancin at 1,500 mg and at 1, 2, 3, 4, and 6 h and 7 and 14 days postadministration. Concentration-time data were analyzed via noncompartmental analysis. Pharmacodynamic parameters against common infectious peritonitis-causing pathogens were evaluated. Ten patients were enrolled. Patients were a median of 55 years old and had a median weight of 78.2 kg, 50% were female, and 70% were Caucasian. The terminal plasma half-life of dalbavancin was 181.4 ± 35.5 h. The day 0 to day 14 dalbavancin mean area under the curve (AUC) was 40,573.2 ± 9,800.3 mg·h/liter. The terminal-phase half-life of dalbavancin within the peritoneal fluid was 4.309 x 10⁸ ± 1.140 x 10⁹ h. The day 0 to day 14 dalbavancin mean peritoneal fluid AUC was 2,125.0 ± 1,794.3 mg·h/liter. The target plasma AUC/MIC was attained with the intravenous dose in all 10 patients for all Staphylococcus and Streptococcus species at the recommended MIC breakpoints. The intraperitoneal arm of the study was stopped early, because the first 3 patients experienced moderate to severe pain and bloating within 1 h following the administration of dalbavancin. Dalbavancin at 1,500 mg administered intravenously can be utilized without dose adjustment in peritoneal dialysis patients and will likely achieve the necessary peritoneal fluid concentrations to treat peritonitis caused by typical Gram-positive pathogens.

Cefiderocol inhibited 97.5% of 478 Gram-negative isolates from cancer patients at ≤4 mg/liter. It had potent activity against extended-spectrum β-lactamase-positive Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CRE), and nonfermenting Gram-negative bacilli, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter species isolates. Amikacin, ceftazidime-avibactam, and meropenem had appreciable activity against non-CRE Enterobacteriaceae. No comparators were active against multidrug-resistant P. aeruginosa isolates. Only trimethoprim-sulfamethoxazole had appreciable activity against S. maltophilia isolates. Overall, cefiderocol was associated with the lowest level of resistance.

Antituberculosis (anti-TB) drug development is dependent on informative trials to secure the development of new antibiotics and combination regimens. Clofazimine (CLO) and pyrazinamide (PZA) are important components of recommended standard multidrug treatments of TB. Paradoxically, in a phase IIa trial aiming to define the early bactericidal activity (EBA) of CLO and PZA monotherapy over the first 14 days of treatment, no significant drug effect was demonstrated for the two drugs using traditional statistical analysis. Using a model-based analysis, we characterized the statistically significant exposure-response relationships for both drugs that could explain the original findings of an increase in the numbers of CFU with CLO treatment and no effect with PZA. Sensitive analyses are crucial for exploring drug effects in early clinical trials to make the right decisions for advancement to further development. We propose that this quantitative semimechanistic approach provides a rational framework for analyzing phase IIa EBA studies and can accelerate anti-TB drug development.

In India and China, indigenous drug manufacturers market arbitrarily combined parenteral β-lactam and β-lactamase inhibitors (BL-BLIs). In these fixed-dose combinations, sulbactam or tazobactam is indiscriminately combined with parenteral cephalosporins, with BLI doses kept in ratios similar to those for the approved BL-BLIs. Such combinations have been introduced into clinical practice without mandatory drug development studies involving pharmacokinetic/pharmacodynamic, safety, and efficacy assessments being undertaken. Such unorthodox combinations compromise clinical outcomes and also potentially contribute to resistance development.

In patients with renal impairment (n = 22 of 39), the median serum concentrations of linezolid, PNU-142300, and PNU-142586 were 1.6-, 3.3-, 2.8-fold higher, respectively, than in patients without renal impairment. Metabolite concentrations in paired samples were poorly correlated with linezolid concentrations (r² = 0.26 for PNU-142300 and 0.06 for PNU-142586). Linezolid and its metabolites share potential toxicophores that deserve characterization to mitigate higher myelosuppression risk in patients with renal impairment.

Genomic analysis of a patient's tumor is the cornerstone of precision oncology, but it does not address whether metastases should be treated differently. Here we tested whether comparative single-cell RNA sequencing (scRNA-seq) of a primary small intestinal neuroendocrine tumor to a matched liver metastasis could guide the treatment of a patient's metastatic disease. Following surgery, the patient was put on maintenance treatment with a somatostatin analog. However, the scRNA-seq analysis revealed that the neuroendocrine epithelial cells in the liver metastasis were less differentiated and expressed relatively little SSTR2, the predominant somatostatin receptor. There were also differences in the tumor microenvironments. RNA expression of vascular endothelial growth factors was higher in the primary tumor cells, reflected by an increased number of endothelial cells. Interestingly, vascular expression of the major VEGF receptors was considerably higher in the liver metastasis, indicating that the metastatic vasculature may be primed for expansion and susceptible to treatment with angiogenesis inhibitors. The patient eventually progressed on Sandostatin, and although consideration was given to adding an angiogenesis inhibitor to her regimen, her disease progression involved non-liver metastases that had not been characterized. Although in this specific case comparative scRNA-seq did not alter treatment, its potential to help guide therapy of metastatic disease was clearly demonstrated.

This study was an analysis of a national sample of U.S. medical office visits from 2014 to 2016, a period when evidence of effectiveness was emerging for a variety of beneficial type 2 diabetes agents with regard to potential reduction in diabetes comorbidities. Ideal therapy was defined as an American Diabetes Association–identified beneficial agent plus metformin. The associations between atherosclerotic cardiovascular disease or obesity and use of these agents were explored.

Researchers investigated pain perception in patients with diabetic foot ulcers (DFUs) by analyzing pre- and postoperative physical function (PF), pain interference (PI), and depression domains of the Patient-Reported Outcome Measurement Information System (PROMIS). They hypothesized that 1) because of painful diabetic peripheral neuropathy (DPN), a majority of patients with DFUs would have high PROMIS PI scores unchanged by operative intervention, and 2) the initially assessed PI, PF, and depression levels would be correlated with final outcomes. Seventy-five percent of patients with DFUs reported pain, most likely because of painful DPN. Those who reported high PI and low PF were likely to report depression. PF, PI, and depression levels were unchanged after operative intervention or healing of DFUs.

Background:

Limited treatment options are available for oral mucositis, a common, debilitating complication of cancer therapy. We examined the association between daily delivery time of radiotherapy and the severity of oral mucositis in patients with head and neck cancer.

Background:

The recent expansion of treatment options in acute myeloid leukemia (AML) has necessitated a greater understanding of patient preferences for treatment benefits, about which little is known.

Skeletal muscle wasting is a devastating consequence of cancer that contributes to increased complications and poor survival, but is not well understood at the molecular level. Herein, we investigated the role of Myocilin (Myoc), a skeletal muscle hypertrophy-promoting protein that we showed is downregulated in multiple mouse models of cancer cachexia. Loss of Myoc alone was sufficient to induce phenotypes identified in mouse models of cancer cachexia, including muscle fiber atrophy, sarcolemmal fragility, and impaired muscle regeneration. By 18 months of age, mice deficient in Myoc showed significant skeletal muscle remodeling, characterized by increased fat and collagen deposition compared with wild-type mice, thus also supporting Myoc as a regulator of muscle quality. In cancer cachexia models, maintaining skeletal muscle expression of Myoc significantly attenuated muscle loss, while mice lacking Myoc showed enhanced muscle wasting. Furthermore, we identified the myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain of function significantly deterred cancer-induced muscle wasting and dysfunction in a preclinical model of pancreatic ductal adenocarcinoma (PDAC). Finally, compared with noncancer control patients, MYOC was significantly reduced in skeletal muscle of patients with PDAC defined as cachectic and correlated with MEF2c. These data therefore identify disruptions in MEF2c-dependent transcription of Myoc as a novel mechanism of cancer-associated muscle wasting that is similarly disrupted in muscle of patients with cachectic cancer.Significance:This work identifies a novel transcriptional mechanism that mediates skeletal muscle wasting in murine models of cancer cachexia that is disrupted in skeletal muscle of patients with cancer exhibiting cachexia.

BACKGROUND AND PURPOSE:

Endovascular embolization only has been advocated for treatment of brain arteriovenous malformations in recent trials. Our aim was to evaluate the results of embolization only in a cohort of patients who were enrolled in the A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) study at 39 clinical sites in 9 countries.

Clinicians from two hospitals in Boston report that the majority of even the sickest patients with COVID-19 -- those who require ventilators in intensive care units -- get better when they receive existing guideline-supported treatment for respiratory failure.

A new report offers insights that can help clinicians distinguish between patients with COVID-19 infections and those with other conditions that may mimic COVID-19 symptoms.

The tech giant has often been accused of mistreating workers, but our desire for instant gratification is part of the problem

Tim Bray resigned as an Amazon vice-president last week. “Who he?” I hear you say. And why is this news significant? Answers: first, Bray is an ubergeek who’s an alumnus of many of the outfits in tech’s hall of fame (including DEC, Sun Microsystems, the OED project at the University of Waterloo, Google’s Android team and, eventually, Amazon Web Services); and second, he resigned on an issue of principle – something as rare as hen’s teeth in the tech industry.

In his blog, he wrote: “I quit in dismay at Amazon firing whistleblowers who were making noise about warehouse employees frightened of Covid-19.” It was an expensive decision. Bray said the decision to resign would probably cost him more than a million dollars in salary and shares, and that he regretted leaving a job he enjoyed, working with good colleagues. “So I’m pretty blue.”

Groups across the country are putting tablets in the hands of COVID patients so their families can see them, sometimes for the last time

If there's a ventilator shortage, doctors and ethicists say priority should be given to people with the best chance of recovery and most years likely left to live

Growing evidence suggests the covid-19 outbreak may not have started at Wuhan’s Huanan Seafood Market in December after all. Finding its origins may help us stop it happening again

Our brains influence all aspects of our lives, including our sexual desires. This means brain injuries can have some surprising effects, says Amee Baird

Almost 200,000 surgeries and other procedures were shelved indefinitely, as hospitals braced for a deluge that never quite materialized

The novel coronavirus has been discovered in the semen of infected male individuals, according to Chinese researchers, potentially raising the prospect that the virus could potentially be sexually transmitted.