Empiric treatment of patients with sepsis and septic shock and place in therapy of cefiderocol: a systematic review and expert opinion statement.

Carbapenem-resistant Gram-negative bacteria are frequent causes of sepsis and septic shock in intensive care unit (ICU) and thus considered a public health threat. Until now, the best available therapies consist of combinations of preexisting or new antibiotics with ß-lactamase inhibitors (either new or preexisting). Several mechanisms of resistance, especially those mediated by metallo-ß-lactamases (MBL), are responsible for the inefficacy of these treatments, leaving an unmet medical need. Intravenous cefiderocol has been recently approved by the American Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of complicated urinary tract infections and nosocomial pneumonia due to Gram-negative, when limited therapeutical options are available. In addition, its ability to hijack bacterial iron uptake mechanisms makes cefiderocol stable against the whole Ambler ß-lactamase inhibitors and increases the in vitro efficacy against Gram-negative pathogens (e.g., Enterobacterales spp., Pseudomonas aeruginosa, and Acinetobacter baumannii). Trials have already demonstrated their non-inferiority to comparators. In 2021, ESCMID guidelines released a conditional recommendation supporting the use of cefiderocol against metallo-ß-lactamase-producing Enterobacterales and against Acinetobacter baumannii. This review provides the opinion of experts about the general management of empiric treatment of patients with sepsis and septic shock in the intensive care unit and detects the proper place in therapy of cefiderocol considering recent evidence sought through a systematic search.

Cardiac arrest during a diving session: A case report and differential diagnosis.

We report a case of out-of-hospital cardiac arrest occurred in a 61-year-old recreational female diver. After resuscitation, the patient was referred to the hospital. With data provided by witnesses and appropriate medical investigations, drowning related to a failed rebreather system was the most plausible explanation. Patient outcome was favorable.

Ventilator-Associated Pneumonia in Patients with COVID-19: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to estimate the pooled occurrence of ventilator-associated pneumonia (VAP) among patients admitted to an intensive care unit with COVID-19 and mortality of those who developed VAP. We performed a systematic search on PubMed, EMBASE and Web of Science from inception to 2nd March 2021 for nonrandomized studies specifically addressing VAP in adult patients with COVID-19 and reporting data on at least one primary outcome of interest. Random effect single-arm meta-analysis was performed for the occurrence of VAP and mortality (at the longest follow up) and ICU length of stay. Twenty studies were included in the systematic review and meta-analysis, for a total of 2611 patients with at least one episode of VAP. The pooled estimated occurrence of VAP was of 45.4% (95% C.I. 37.8-53.2%; 2611/5593 patients; I2 = 96%). The pooled estimated occurrence of mortality was 42.7% (95% C.I. 34-51.7%; 371/946 patients; I2 = 82%). The estimated summary estimated metric mean ICU LOS was 28.58 days (95% C.I. 21.4-35.8; I2 = 98%). Sensitivity analysis showed that patients with COVID-19 may have a higher risk of developing VAP than patients without COVID-19 (OR 3.24; 95% C.I. 2.2-4.7; P = 0.015; I2 = 67.7%; five studies with a comparison group).

Endocrine Challenges in Patients with Continuous-Flow Left Ventricular Assist Devices.

Heart failure (HF) remains a leading cause of morbidity, hospitalization, and mortality worldwide. Advancement of mechanical circulatory support technology has led to the use of continuous-flow left ventricular assist devices (LVADs), reducing hospitalizations, and improving quality of life and outcomes in advanced HF. Recent studies have highlighted how metabolic and endocrine dysfunction may be a consequence of, or associated with, HF, and may represent a novel (still neglected) therapeutic target in the treatment of HF. On the other hand, it is not clear whether LVAD support, may impact the outcome by also improving organ perfusion as well as improving the neuro-hormonal state of the patients, reducing the endocrine dysfunction. Moreover, endocrine function is likely a major determinant of human homeostasis, and is a key issue in the recovery from critical illness. Care of the endocrine function may contribute to improving cardiac contractility, immune function, as well as infection control, and rehabilitation during and after a LVAD placement. In this review, data on endocrine challenges in patients carrying an LVAD are gathered to highlight pathophysiological states relevant to this setting of patients, and to summarize the current therapeutic suggestions in the treatment of thyroid dysfunction, and vitamin D, erythropoietin and testosterone administration.

Citations and metrics of journals discontinued from Scopus for publication concerns: the GhoS(t)copus Project.

Background: Scopus is a leading bibliometric database. It contains the largest number of articles cited in peer-reviewed publications . The journals included in Scopus are periodically re-evaluated to ensure they meet indexing criteria and some journals might be discontinued for publication concerns. These journals remain indexed and can be cited. Their metrics have yet to be studied. This study aimed  to evaluate the main features and metrics of journals discontinued from Scopus for publication concerns, before and after their discontinuation, and to determine the extent of predatory journals among the discontinued journals. Methods: We surveyed the list of discontinued journals from Scopus (July 2019). Data regarding metrics, citations and indexing were extracted from Scopus or other scientific databases, for the journals discontinued for publication concerns.  Results: A total of 317 journals were evaluated. Ninety-three percent of the journals (294/318) declared they published using an Open Access model. The subject areas with the greatest number of discontinued journals were  Medicine (52/317; 16%),  Agriculture and Biological Science (34/317; 11%), and  Pharmacology, Toxicology and Pharmaceutics (31/317; 10%). The mean number of citations per year after discontinuation was significantly higher than before (median of difference 64 citations, p<0.0001), and so was the number of citations per document (median of difference 0.4 citations, p<0.0001). Twenty-two percent (72/317) were included in the Cabell's blacklist. The DOAJ currently included only 9 journals while 61 were previously included and discontinued, most for 'suspected editorial misconduct by the publisher'. Conclusions: The citation count of journals discontinued for publication concerns increases despite discontinuation and predatory behaviors seemed common. This paradoxical trend can inflate scholars' metrics prompting artificial career advancements, bonus systems and promotion. Countermeasures should be taken urgently to ensure the reliability of Scopus metrics both at the journal- and author-level for the purpose of scientific assessment of scholarly publishing.

Update I. A systematic review on the efficacy and safety of chloroquine/hydroxychloroquine for COVID-19.

PURPOSE: To assess efficacy and safety of chloroquine (CQ)/hydroxychloroquine (HCQ) for treatment or prophylaxis of COVID-19 in adult humans. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Ceftazidime-Avibactam Combination Therapy Compared to Ceftazidime-Avibactam Monotherapy for the Treatment of Severe Infections Due to Carbapenem-Resistant Pathogens: A Systematic Review and Network Meta-Analysis.

Ceftazidime-avibactam (CZA) is a novel beta-lactam beta-lactamase inhibitor combination approved for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and for hospital-acquired/ventilator-associated pneumonia. The aim of this systematic review (PROSPERO registration number: CRD42019128927) was to evaluate the effectiveness of CZA combination therapy versus CZA monotherapy in the treatment of severe infections. The databases included in the search, until February 12th, 2020, were MEDLINE by PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized studies published in peer-reviewed journals and in the English language. The primary outcome was all-cause mortality (longest follow-up) evaluated in patients with the diagnosis of infection with at least one pathogen; secondary outcomes were clinical and microbiological improvement/cure. Thirteen studies were included in the qualitative synthesis: 7 RCTs and 6 retrospective studies All the six retrospective studies identified carbapenamase-producing Enterobacteriaceae (CRE) as the cause of infection and for this reason were included in the network meta-analysis (NMA); the quality of the studies, assessed using the New Castle-Ottawa Scale, was moderate-high. In all the six retrospective studies included in the NMA, CZA was used in large part for off-label indications (mostly blood stream infections: 80-100% of patients included). No difference in mortality rate was observed in patients undergoing CZA combination therapy compared to CZA monotherapy [n = 503 patients, direct evidence OR: 0.96, 95% CI: 0.65-1.41].

Association between night/after-hours surgery and mortality: a systematic review and meta-analysis.

BACKGROUND: The association between night/after-hours surgery and patients' mortality is unclear. METHODS: The protocol of this systematic review was registered in PROSPERO (CRD42019128534). We searched Medline, PubMed, and EMBASE from inception until August 29, 2019 for studies examining an association between timing of surgical procedures (time of anaesthesia induction or surgery start) and mortality (within 30 days or in-hospital) in adult patients. Studies reporting patients' mortality after surgery performed during the weekend only were excluded. All analyses were done using the random-effects model. RESULTS: We included 40 observational studies (36 retrospective and four prospective) that examined a total of 2 957 065 patients. Twenty-eight studies were judged of good quality and 12 of poor quality according to Newcastle-Ottawa score, owing to a lack of adequate comparability between study groups. Primary analysis from adjusted estimates demonstrated as association between night/after-hours surgery and a higher risk of mortality (odds ratio [OR]=1.16; 95% confidence interval [CI], 1.06-1.28; P=0.002; number of studies=18; I2=67%) based on low certainty evidence. Analysis from unadjusted estimates demonstrated a consistent association (OR=1.47; 95% CI, 1.19-1.83; P=0.0005; studies=38, I2=97%; low certainty). The number of centres per study had no credible subgroup effect on the association between the time of surgery and mortality. We were unable to evaluate the subgroup effect of urgency of surgery because of high heterogeneity. CONCLUSIONS: Night/after-hours surgery may be associated with a higher risk of mortality. Patients' and surgical characteristics seem not to completely explain this finding. However, the certainty of the evidence was low.

A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19.

PURPOSE: 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. METHODS: PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19. RESULTS: 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. CONCLUSIONS: 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.

Fake news and patient-family-physician interaction in critical care: concepts, beliefs and potential countermeasures.

Fake news has been defined as fabricated information mimicking media content in form but not in organizational process or intent. Science and medicine are deeply affected by this increasing phenomenon. Critical care represents a hot spot for fake news due to the high risk of conflictive communication, the rapid turnaround of clinical news and high prevalence of unpleasant information. Communication with patients' relatives is one of the hardest aspects. The relationship between physicians and families is pivotal to improve relatives' comfort, and reduce anxiety and pain. Fake news may undermine this relationship, posing an alternative truth between the critical care physician and relatives, which must be countered without worsening their suffering. The aim of this review is to provide intensivists an overview of concepts, characteristics and risk to better understand the fake news phenomenon and counter its potentially devastating effects.