Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung. IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD.

The accumulated and analyzed evidence suggests that conservative treatment, type I emphysematous pyelonephritis, bilateral emphysematous pyelonephritis and thrombocytopenia seem to be significant risk factors for mortality in patients with emphysematous pyelonephritis. These data may be taken into consideration when treating patients with this devastating infection.

No abstract

PURPOSE Whether cancer is associated with worse prognosis among patients with COVID-19 is unknown. We aimed to quantify the effect (if any) of the presence as opposed to absence of cancer on important clinical outcomes of patients with COVID-19 by carrying out a systematic review and meta-analysis. METHODS We systematically searched PubMed, medRxiv, COVID-19 Open Research Dataset (CORD-19), and references of relevant articles up to April 27, 2020, to identify observational studies comparing patients with versus without cancer infected with COVID-19 and to report on mortality and/or need for admission to the intensive care unit (ICU). We calculated pooled risk ratios (RR) and 95% CIs with a random-effects model. The meta-analysis was registered with PROSPERO (CRD42020181531). RESULTS A total of 32 studies involving 46,499 patients (1,776 patients with cancer) with COVID-19 from Asia, Europe, and the United States were included. All-cause mortality was higher in patients with versus those without cancer (2,034 deaths; RR, 1.66; 95% CI, 1.33 to 2.07; P < .0001; 8 studies with 37,807 patients). The need for ICU admission was also more likely in patients with versus without cancer (3,220 events; RR, 1.56; 95% CI, 1.31 to 1.87; P < .0001; 26 studies with 15,375 patients). However, in a prespecified subgroup analysis of patients > 65 years of age, all-cause mortality was comparable between those with versus without cancer (915 deaths; RR, 1.06; 95% CI, 0.79 to 1.41; P = .71; 8 studies with 5,438 patients). CONCLUSION The synthesized evidence suggests that cancer is associated with worse clinical outcomes among patients with COVID-19. However, elderly patients with cancer may not be at increased risk of death when infected with COVID-19. These findings may inform discussions of clinicians with patients about prognosis and may guide health policies.

Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

BackgroundThe Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Task Force recently introduced a new clinical score termed quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) for identification of patients at risk of sepsis outside the intensive care unit (ICU). We attempted to compare the discriminatory capacity of the qSOFA versus the Systemic Inflammatory Response Syndrome (SIRS) score for predicting mortality, ICU-free days, and organ dysfunction-free days in patients with suspicion of infection outside the ICU.MethodsThe Weill Cornell Medicine Registry and Biobank of Critically Ill Patients is an ongoing cohort of critically ill patients, for whom biological samples and clinical information (including vital signs before and during ICU hospitalization) are prospectively collected. Using such information, qSOFA and SIRS scores outside the ICU (specifically, within 8 hours before ICU admission) were calculated. This study population was therefore comprised of patients in the emergency department or the hospital wards who had suspected infection, were subsequently admitted to the medical ICU and were included in the Registry and Biobank.ResultsOne hundred fifty-two patients (67% from the emergency department) were included in this study. Sixty-seven percent had positive cultures and 19% died in the hospital. Discrimination of in-hospital mortality using qSOFA [area under the receiver operating characteristic curve (AUC), 0.74; 95% confidence intervals (CI), 0.66–0.81] was significantly greater compared with SIRS criteria (AUC, 0.59; 95% CI, 0.51–0.67; p = 0.03). The qSOFA performed better than SIRS regarding discrimination for ICU-free days (p = 0.04), but not for ventilator-free days (p = 0.19), any organ dysfunction-free days (p = 0.13), or renal dysfunction-free days (p = 0.17).ConclusionsIn patients with suspected infection who eventually required admission to the ICU, qSOFA calculated before their ICU admission had greater accuracy than SIRS for predicting mortality and ICU-free days. However, it may be less clear whether qSOFA is also better than SIRS criteria for predicting ventilator free-days and organ dysfunction-free days. These findings may help clinicians gain further insight into the usefulness of qSOFA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1658-5) contains supplementary material, which is available to authorized users.

No abstract

Administration of probiotics is associated with lower incidence of ventilator-associated pneumonia than control. Given the increasing antimicrobial resistance, this promising strategy deserves consideration in future studies, which should have active surveillance for probiotic-induced diseases.