Background: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. Methods: This systematic review was registered at PROSPERO under CRD42020177154. We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31^st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. Results: Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10 mg/L, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49 U/L, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88 pg/mL, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 to 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). Discussion: This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors that predict severe COVID-19 outcomes and will inform clinical scores to support early decision-making.

Scope: Preclinical models have demonstrated the anti‐inflammatory and lipid‐lowering effects of curcumin. Innovative formulations have been developed to overcome the poor bioavailability of native curcumin. The study hypothesizes that the bioavailability of micellar curcumin is superior to native curcumin and investigates the potential anti‐inflammatory and proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration lowering effects.Methods and results: In this double‐blind, randomized, crossover trial, 15 healthy volunteers receive micellar or native curcumin (105 mg day⁻¹) for 7 days with a ≥7 days washout period. Curcumin and metabolite concentrations are quantified by high‐performance liquid chromatography with fluorescence detection (HPLC‐FD), and pharmacokinetics are calculated. To analyze anti‐inflammatory effects, blood samples (baseline, 2 h, 7 days) are stimulated with 50 ng mL⁻¹lipopolysaccharides (LPS). Interleukin (IL)‐6, tumor‐necrosis factor (TNF‐α), and PCSK9 concentrations are quantified. Micellar curcumin demonstrates improved bioavailability (≈39‐fold higher maximum concentrations, ≈14‐fold higher area‐under‐the‐time‐concentration curve,p< 0.001) but does not reduce pro‐inflammatory cytokines in the chosen model. Subjects receiving micellar curcumin have significantly lower PCSK9 concentrations (≈10% reduction) after 7 days compared to baseline (p= 0.038).Conclusion: Micellar curcumin demonstrates an improved oral bioavailability but does not show anti‐inflammatory effects in this model. Potential effects on PCSK9 concentrations warrant further investigation.

Prior studies suggest that the use of personal protective equipment might impair the quality of critical care. We investigated the influence of personal protective equipment on out-of-hospital cardiopulmonary resuscitation. Randomised controlled non-inferiority triple-crossover study. Forty-eight emergency medical service providers, randomized into teams of two, performed 12 min of basic life support (BLS) on a manikin after climbing 3 flights of stairs. Three scenarios were completed in a randomised order: Without personal protective equipment, with personal protective equipment including a filtering face piece (FFP) 2 mask with valve, and with personal protective equipment including an FFP2 mask without valve. The primary outcome was mean depth of chest compressions with a pre-defined non-inferiority margin of 3.5 mm. Secondary outcomes included other measurements of CPR quality, providers' subjective exhaustion levels, and providers' vital signs, including end-tidal CO2. Differences regarding the primary outcome were well below the pre-defined non-inferiority margins for both control vs. personal protective equipment without valve (absolute difference 1 mm, 95% CI [-1, 2]) and control vs. personal protective equipment with valve (absolute difference 1 mm, [-0.2, 2]). This was also true for secondary outcomes regarding quality of chest compressions and providers' vital signs including etCO2. Subjective physical strain after BLS was higher in the personal protective equipment groups (Borg 4 (SD 3) without valve, 4 (SD 2) with valve) than in the control group (Borg 3 (SD 2)). PPE including masks with and without expiration valve is safe for use without concerns regarding the impairment of CPR quality.

The International Society of Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score is widely used to predict mortality in critically ill - typically septic - patients. The objective of this study was to investigate whether the ISTH DIC-2001 and DIC-2018 score can be used to predict the 30-day mortality in non-septic patients in an intensive care unit (ICU). In this single-center, prospective observational study we included all patients ≥18 years of age who were admitted to a medical ICU with a focus on cardiovascular diseases between August 2012 and 2013. The DIC-2001 and DIC-2018 scores were calculated on admission (DIC-2001-0h and DIC-2018-0h) and 72 hours thereafter (DIC-2001-72h and DIC-2018-72h) and were classified as overt when ≥ 5 for DIC-2001 and ≥ 4 for DIC-2018. A total of 233 patients were included in this study. Excluding septic patients and patients after routine surgery/procedures, we calculated the DIC score for 167 patients (32.4% female; median age 64.9 years). Overt DIC-2001-0h, DIC-2018-0h and overt DIC-2001-72h scores were associated with a significantly higher 30-day mortality rate (52.9% vs. 25.0%, 46.2% vs 21.2%, and 57.1% vs. 23.7%; p < 0.04). The DIC-2001 scores and the DIC-2018-0h score significantly predicted the 30-day mortality. This study suggests that the DIC score may be applied to non-septic ICU populations, and indicates that it is a useful tool for mortality prediction, regardless of the underlying disease.

Background: In cardiac arrest survivors, metabolic parameters [pH value, lactate concentration, and base deficit (BD)] are routinely added to peri-arrest factors (including age, sex, bystander cardiopulmonary resuscitation, shockable first rhythm, resuscitation duration, adrenaline dose) to enhance early outcome prediction. However, the additional value of this strategy remains unclear.Methods: We used our resuscitation database to screen all patients ≥18 years who had suffered in- or out-of-hospital cardiac arrest (IHCA, OHCA) between January 1st, 2005 and May 1st, 2019. Patients with incomplete data, without return of spontaneous circulation or treatment with sodium bicarbonate were excluded. To analyse the added value of metabolic parameters to prognosticate neurological function, we built three models using logistic regression. These models included: (1) Peri-arrest factors only, (2) peri-arrest factors plus metabolic parameters and (3) metabolic parameters only. Receiver operating characteristics curves regarding 30-day good neurological function (Cerebral Performance Category 1-2) were analysed.Results: A total of 2,317 patients (OHCA: n = 1842) were included. In patients with OHCA, model 1 and 2 had comparable predictive value. Model 3 was inferior compared to model 1. In IHCA patients, model 2 performed best, whereas both metabolic (model 3) and peri-arrest factors (model 1) demonstrated similar power. PH, lactate and BD had interchangeable areas under the curve in both IHCA and OHCA.Conclusion: Although metabolic parameters may play a role in IHCA, no additional value in the prediction of good neurological outcome could be found in patients with OHCA. This highlights the importance of accurate anamnesis especially in patients with OHCA.

In former studies, the arterio-alveolar carbon dioxide gradient (ΔCO₂) predicted in-hospital mortality after initially survived cardiac arrest. As early outcome predictors are urgently needed, we evaluated ΔCO₂ as predictor for good neurological outcome in our cohort. We retrospectively analyzed all patients ≥18 years of age after non-traumatic in- and out of hospital cardiac arrest in the year 2018 from our resuscitation database. Patients without advanced airway management, incomplete datasets or without return of spontaneous circulation were excluded. The first arterial pCO₂ after admission and the etCO₂ in mmHg at the time of blood sampling were recorded from patient's charts. We then calculated ΔCO₂ (pCO₂ - etCO₂). For baseline analyses, ΔCO₂ was dichotomized into a low and high group with separation at the median. Good neurological outcome on day 30, expressed as Cerebral Performance Category 1-2, defined our primary endpoint. Survival to 30 days was used as secondary endpoint. Out of 302 screened patients, 128 remained eligible for analyses. ΔCO₂ was lower in 30-day survivors with good neurological outcome (12.2 mmHg vs. 18.8 mmHg, p = 0.009) and in 30-day survivors (12.5 mmHg vs. 20.0 mmHg, p = 0.001). In patients with high ΔCO₂, a cardiac etiology of arrest was found less often. They had a higher body mass index, longer duration of resuscitation, higher amounts of epinephrine, lower pO₂ levels but both higher pCO2 and blood lactate levels, resulting in lower blood pH and HCO₃^- levels at admission. In a crude binary logistic regression analysis, ΔCO₂ was associated with 30-day neurological outcome (OR = 1.041 per mmHg of ΔCO₂, 95% CI 1.008-1.074, p = 0.014). This association persisted after the adjustment for age, sex, witnessed arrest and shockable first rhythm. However, after addition of the duration of resuscitation or the cumulative epinephrine dosage to the model, ΔCO₂ lost its association. ΔCO₂ at admission after a successfully resuscitated cardiac arrest is associated with 30 days survival with good neurological outcome. However, a higher ΔCO₂ may rather be a surrogate for unfavorable resuscitation circumstances than an independent outcome predictor.