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COVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chloroquine for the treatment of COVID-19. PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19. We included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro. There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed. •No specific pharmacological treatments are available to date for COVID-19.•Chloroquine is a widely used, safe and cheap, effective in viral infections in pre-clinical studies.•Specific pre-clinical evidence and expert opinions suggest potential use against SARS-CoV-2.•A search in trial registries shows that 23 clinical trials are ongoing in China.•There is a urgent need of high-quality clinical data from different geographic areas.

Palliative care is patient and family-centered care that optimizes quality of life by anticipating, preventing, and treating suffering when “curative” therapies are futile. In the Intensive Care Unit (ICU), critically ill patients receive life-sustaining therapies with the goal of restoring or maintaining organ function. Palliative Care in the ICU is a widely discussed topic and it is increasingly applied in clinics. It encompasses symptoms control and end-of-life management, communication with relatives and setting goals of care ensuring dignity in death and decision-making power. However, effective application of Palliative Care in ICU presupposes specific knowledge and training which anesthesiologists and critical care physicians may lack. Moreover, logistic issues such protocols for patients’ selection, application models and triggers for consultation of external experts are still matter of debate. The aim of this review is to provide the anesthesiologists and intensivists an overview of the aims, current evidence and practical advices about the application of palliative care in ICU.

Background The mortality of critically ill patients with COVID-19 is high, particularly among those receiving mechanical ventilation (MV). Despite the high number of patients treated worldwide, data on respiratory mechanics are currently scarce and the optimal setting of MV remains to be defined. This scoping review aims to provide an overview of available data about respiratory mechanics, gas exchange and MV settings in patients admitted to intensive care units (ICUs) for COVID-19-associated acute respiratory failure, and to identify knowledge gaps. Main text PubMed, EMBASE, and MEDLINE databases were searched from inception to October 30, 2020 for studies providing at least one ventilatory parameter collected within 24 h from the ICU admission. The quality of the studies was independently assessed using the Newcastle–Ottawa Quality Assessment Form for Cohort Studies. A total of 26 studies were included for a total of 14,075 patients. At ICU admission, positive end expiratory pressure (PEEP) values ranged from 9 to 16.5 cm of water (cmH 2 O), suggesting that high levels of PEEP were commonly used for setting MV for these patients. Patients with COVID-19 are severely hypoxemic at ICU admission and show a median ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 ) ranging from 102 to 198 mmHg. Static respiratory system compliance (Crs) values at ICU admission were highly heterogenous, ranging between 24 and 49 ml/cmH 2 O. Prone positioning and neuromuscular blocking agents were widely used, ranging from 17 to 81 and 22 to 88%, respectively; both rates were higher than previously reported in patients with “classical” acute respiratory distress syndrome (ARDS). Conclusions Available data show that, in mechanically ventilated patients with COVID-19, respiratory mechanics and MV settings within 24 h from ICU admission are heterogeneous but similar to those reported for “classical” ARDS. However, to date, complete data regarding mechanical properties of respiratory system, optimal setting of MV and the role of rescue treatments for refractory hypoxemia are still lacking in the medical literature.

Candida spp . infections are a major cause of morbidity and mortality in critically ill patients. Candida auris is an emerging multi-drug-resistant fungus that is rapidly spreading worldwide. Since the first reports in 2009, many isolates across five continents have been identified as agents of hospital-associated infections. Independent and simultaneous outbreaks of C. auris are becoming a major concern for healthcare and scientific community. Moreover, laboratory misidentification and multi-drug-resistant profiles, rarely observed for other non-albicans Candida species, result in difficult eradication and frequent therapeutic failures of C. auris infections. The aim of this review was to provide an updated and comprehensive report of the global spread of C. auris , focusing on clinical and microbiological characteristics, mechanisms of virulence and antifungal resistance, and efficacy of available control, preventive, and therapeutic strategies.

Background The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO 2 clearance after 2 h of treatment. Methods We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25–7.35, PaCO 2  ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO 2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO 2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. Results Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO 2 reduction from baseline to 2 h were − 6.8 mmHg (± 8.7) in the HFNT and − 9.5 mmHg (± 8.5) in the NIV group ( p  = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO 2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p  = 0.0003). Both treatments had a significant effect on PaCO 2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. Conclusions HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO 2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. Trial registration : The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

To assess efficacy and safety of chloroquine (CQ)/hydroxychloroquine (HCQ) for treatment or prophylaxis of COVID-19 in adult humans. MEDLINE, PubMed, EMBASE and two pre-print repositories (bioRxiv, medRxiv) were searched from inception to 8th June 2020 for RCTs and nonrandomized studies (retrospective and prospective, including single-arm, studies) addressing the use of CQ/HCQ in any dose or combination for COVID-19. Thirty-two studies were included (6 RCTs, 26 nonrandomized, 29,192 participants). Two RCTs had high risk, two ‘some concerns’ and two low risk of bias (Rob2). Among nonrandomized studies with comparators, nine had high risk and five moderate risk of bias (ROBINS-I). Data synthesis was not possible. Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low. Patients with COVID-19 should be treated with CQ/HCQ only if monitored and within the context of high quality RCTs. High quality data about efficacy/safety are urgently needed. •As of June 2020 there is no high quality evidence regarding hydroxychloroquine (HCQ) as treatment or prophylaxis of COVID-19.•Treatment with HCQ may be associated with no reduction of in-hospital death compared to standard care.•High dosages, comorbidities and combinations with macrolides may increase the risk of death and cardiac adverse events.•Post-exposure prophylaxis with HCQ probably has no effect on preventing COVID-19-like symptoms.•HCQ should not be used outside high-quality RCTs in patients with COVID-19.

Table 1 Summary of findings in studies of the HFNT with regard to dyspnea, comfort, and respiratory rate Study Type Design Intervention (N) Control (N) Treatment methods Measurement method Dyspnea Comfort Respiratory rate Bell N. [6] Emerg Med Australas 2015 AHRF RCT HFNT (48) COT (52) HFNT: flow 50 L/m, FiO2 30% titrated to SpO2 95% COT: discretion of the treating physician Dyspnea: Borg Scale Comfort: Likert Scale HFNT§ HFNT§ (1 h) HFNT§ (2 h) Frat J.P. [7] N Engl J Med 2015 AHRF RCT HFNT (106) COT (94) NIV (110) HFNT: flow 50 L/m, FiO2 100% then titrated to SpO2 92% COT: O2 titrated to SpO2 94% Dyspnea: VAS Comfort: VAS HFNT§ (10, 15, 30 min) NS HFNT§ (5, 10, 15, 30 min) AHFR acute hypoxemic respiratory failure, ARF acute respiratory failure, CPAP continuous positive airway pressure, COT conventional oxygen therapy, HFNT high-flow nasal treatment, h hours, IPAP inspiratory positive airway pressure, N number of patients, NA not available, NIV noninvasive ventilation, NS not statistically significant, PES esophageal pressure, PSV pressure support ventilation, RCT randomized controlled trial, VAS visual analog scale §Comparison between intervention and control with a statistically significant p value in favor of (the specified intervention) Heterogeneity in case-mix, the tools used for outcome assessment and measurement time-points precluded performance of meta-analysis. N Engl J Med. 2015;372:2185–96.View ArticleGoogle Scholar Lemiale V, Mokart D, Mayaux J, Lambert J, Rabbat A, Demoule A, Azoulay E. The effects of a 2-h trial of high-flow oxygen by nasal cannula versus Venturi mask in immunocompromised patients with hypoxemic acute respiratory failure: a multicenter randomized trial. Ann Emerg Med. 2017;70:465–472 e462.View ArticleGoogle Scholar Azoulay E, Lemiale V, Mokart D, Nseir S, Argaud L, Pene F, Kontar L, Bruneel F, Klouche K, Barbier F, Reignier J, Berrahil-Meksen L, Louis G, Constantin JM, Mayaux J, Wallet F, Kouatchet A, Peigne V, Theodose I, Perez P, Girault C, Jaber S, Oziel J, Nyunga M, Terzi N, Bouadma L, Lebert C, Lautrette A, Bige N, Raphalen JH, Papazian L, Darmon M, Chevret S, Demoule A. Effect of High-Flow Nasal Oxygen vs Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure: The HIGH Randomized Clinical Trial.