An immune-protein score combining TRAIL, IP-10 and CRP for predicting severe COVID-19 disease.

COVID-19 patients are oftentimes over- or under-treated due to a deficit in predictive management tools. This study reports derivation of an algorithm that integrates the host levels of TRAIL, IP-10, and CRP into a single numeric score that is an early indicator of severe outcome for COVID-19 patients and can identify patients at-risk to deteriorate. 394 COVID-19 patients were eligible; 29% meeting a severe outcome (intensive care unit admission/non-invasive or invasive ventilation/death). The score's area under the receiver operating characteristic curve (AUC) was 0.86, superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The score differentiated severe patients who further deteriorated from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001). The score accurately predicted COVID-19 patients at-risk for severe outcome, and therefore has potential to facilitate timely care escalation and de-escalation and appropriate resource allocation.

Tocilizumab Treatment Effect on Iron Homeostasis in Severe COVID-19 Patients.

BACKGROUND: Tocilizumab has been proposed as an effective treatment for severe COVID-19. We aimed to investigate whether tocilizumab administration is associated with increased availability of serum iron which may possibly be associated with adverse effects on clinical outcomes. METHODS: We performed an observational, retrospective cohort study. We included adults, who were hospitalized in ICU with the diagnosis of severe COVID-19 infection eligible for tocilizumab treatment. Laboratory data including serum iron, ferritin, transferrin saturation, hemoglobin, and C-reactive protein levels of all patients were collected shortly before and 24 h, 48 h, and 72 h after tocilizumab administration. RESULTS: During the study period, 15 patients fulfilled the inclusion criteria and were eligible to receive tocilizumab treatment. Tocilizumab therapy was associated with a prominent increase in serum iron and transferrin saturation levels (26 ± 13 µg/dL and 15 ± 8% before treatment and 79 ± 32 µg/dL and 41 ± 15% 72 h after treatment, respectively, p < 0.001) and decrease in serum ferritin levels (1,921 ± 2,071 ng/mL before and 1,258 ± 1,140 ng/mL 72 h after treatment, p = 0.027). CONCLUSION: Treatment of severe COVID-19 patients with tocilizumab is associated with a profound increase in serum iron and ferritin saturation levels along with a decrease in ferritin levels. This may represent an undesirable side effect that may potentiate viral replication.

Accessing unproven interventions in the COVID-19 pandemic: discussion on the ethics of 'compassionate therapies' in times of catastrophic pandemics.

Since the onset of the SARS-CoV-2 pandemic, an array of off-label interventions has been used to treat patients, either provided as compassionate care or tested in clinical trials. There is a challenge in determining the justification for conducting randomised controlled trials over providing compassionate use in an emergency setting. A rapid and more accurate evaluation tool is needed to assess the effect of these treatments. Given the similarity to the Ebola Virus Disease (EVD) pandemic in Africa in 2014, we suggest using a tool designed by the WHO committee in the aftermath of the EVD pandemic: Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI). Considering the uncertainty around SARS-CoV-2, we propose using an improved MEURI including the Plan-Do-Study-Act tool. This combined tool may facilitate dynamic monitoring, analysing, re-evaluating and re-authorising emergency use of unproven treatments and repeat it in cycles. It will enable adjustment and application of outcomes to clinical practice according to changing circumstances and increase the production of valuable data to promote the best standard of care and high-quality research-even during a pandemic.

Development and validation of a knowledge-driven risk calculator for critical illness in COVID-19 patients.

Facing the novel coronavirus disease (COVID-19) pandemic, evidence to inform decision-making at all care levels is essential. Based on the results of a study by Petrilli et al., we have developed a calculator using patient data at admission to predict critical illness (intensive care, mechanical ventilation, hospice care, or death). We report a retrospective validation of the calculator on 145 consecutive patients admitted with COVID-19 to a single hospital in Israel. Despite considerable differences between the original and validation study populations, of 18 patients with critical illness, 17 were correctly identified (sensitivity: 94.4%, 95% CI, 72.7%-99.9%; specificity: 81.9%, 95% CI, 74.1%-88.2%). Of 127 patients with non-critical illness, 104 were correctly identified. Our results indicate that published knowledge can be reliably applied to assess patient risk, potentially reducing the cognitive burden on physicians, and helping policymakers better prepare for future needs.

Non-Invasive Hemodynamic Whole-Body Bioimpedance Indices for the Early Detection of Cancer Treatment-Related Cardiotoxicity: A Retrospective Observational Study.

INTRODUCTION: Patients undergoing chemotherapy are extremely vulnerable to cardiotoxicity. Early detection of cardiac dysfunction is of vital importance to optimize the management of these patients. OBJECTIVE: The aim of this study was to test the effectiveness of non-invasive hemodynamic whole-body bioimpedance (WBI) technology as a modality to detect heart failure in patients undergoing chemotherapy treatment. METHODS: This retrospective observational trial included 84 patients treated at the cardio-oncology outpatient clinic of the Rabin Medical Center. Clinical assessments were performed including biomarker testing and measurement of hemodynamic and volume status parameters as measured by WBI. RESULTS: We included 84 patients with a median age of 64.8 years, and 40.5% were males. Clinical heart failure was detected in 43% of the whole group. Patients were divided into two groups according to baseline NT-proBNP levels with a cut-off of 900 pg/mL. Left ventricular ejection fraction did not differ between the groups. Those with NT-proBNP >900 pg/mL had lower levels of stroke index, cardiac index, and Granov-Goor index (GGI; 25.9 vs. 34.0, 2.0 vs. 2.3, 8.3 vs. 11.4, respectively, with p < 0.001 for all comparisons). The optimal cut-off value for the GGI to detect NT-proBNP >900 pg/mL was 8.3. The area under the curve of a GGI cut-off <8.3 to detect NT-proBNP >900 pg/mL was 0.81 (positive predictive value 95% and negative predictive value 72%), with a 51% sensitivity and 98% specificity. CONCLUSION: GGI, a parameter measured by WBI, can reliably correlate to biomarker evidence of heart failure in patients after chemotherapy. Its use as a screening tool for cardiotoxicity in patients with ongoing anticancer therapy is promising.

Hemodynamic response to fluid removal during hemodialysis: categorization of causes of intradialytic hypotension.

Background: Intradialytic hypotension is a clinically significant problem, however, the hemodynamics that underlie ultrafiltration and consequent hypotensive episodes has not been studied comprehensively. Methods: Intradialytic cardiac output, cardiac power and peripheral resistance changes from pretreatment measurements were evaluated using a novel regional impedance cardiographic device (NICaS, NI Medical, Peta Tikva, Israel) in 263 hemodialysis sessions in 54 patients in dialysis units in the USA and Brazil with the goal of determining the various hemodynamic trends as blood pressure decreases. Results: Hypotensive episodes occurred in 99 (13.5%) of 736 intra- and postdialytic evaluations. The hemodynamic profiles of the episodes were categorized: (i) The cardiac power index significantly decreased in 35% of episodes by 36%, from 0.66 [95% confidence interval (CI) 0.60-0.72] to 0.43 (95% CI 0.37-0.48) [w/m2] with a small reduction in the total peripheral resistance index. (ii) The total peripheral resistance index significantly decreased in 37.4% of episodes by 33%, from 3342 (95% CI 2824-3859) to 2251 (95% CI 1900-2602) [dyn × s/cm5 × m2] with a small reduction in the cardiac power index. (iii) Both the cardiac power index and total peripheral resistance index significantly decreased in 27.3% of episodes, the cardiac power index by 25% from 0.63 (95% CI 0.57-0.70) to 0.48 (95% CI 0.42-0.53) [w/m2] and the total peripheral resistance index by 23% from 2964 (95% CI 2428-3501) to 2266 (95% CI 1891-2642). Conclusions: The hemodynamic profiles clearly define specific hemodynamic mechanisms of cardiac power reduction and/or vasodilatation as underlying intradialytic hypotensive episodes. A reduction in cardiac power (reduction of both blood pressure and cardiac output) could be the result of preload reduction due to a high ultrafiltration rate with not enough refilling or low target weight. A reduction in peripheral resistance (reduction in blood pressure and increase in cardiac output) could be the result of relative vasodilatation as arteries do not contract to compensate for volume reduction due to autonomous dysfunction. As both phenomena are independent, they may appear at the same time. Based on these results, a reduction of ultrafiltration rate and an increase in target weight to improve preload or immediate therapeutic actions to increase peripheral resistance are rational measures that could be taken to maintain blood pressure and prevent hypotensive ischemic complications in dialysis patients.

Maternal cardiovascular hemodynamics in normotensive versus preeclamptic pregnancies: a prospective longitudinal study using a noninvasive cardiac system (NICaS™).

BACKGROUND: Preeclampsia is among the most common medical complications of pregnancy. The clinical utility of invasive hemodynamic monitoring in preeclampsia (e.g., Swan-Ganz catheter) is controversial. Thoracic impedance cardiography (TIC) and Doppler echocardiography are noninvasive techniques but they both have important limitations. NICaS™ (NI Medical, PetachTikva, Israel) is a noninvasive cardiac system for determining cardiac output (CO) that utilizes regional impedance cardiography (RIC) by noninvasively measuring the impedance signal in the periphery. It outperformed any other impedance cardiographic technology and was twice as accurate as TIC. METHODS: We used the NICaS™ system to compare the hemodynamic parameters of women with severe preeclampsia (PET group, n = 17) to a cohort of healthy normotensive pregnant women with a singleton pregnancy at term (control group, n = 62) (1/2015-6/2015). Heart rate (HR), stroke volume (SV), CO, total peripheral resistance (TPR) and mean arterial pressure (MAP) were measured 15-30 min before CS initiation, immediately after administering spinal anesthesia, immediately after delivery of the fetus and placenta, at the abdominal fascia closure and within 24-36 and 48-72 h postpartum. RESULTS: The COs before and during the CS were significantly higher in the control group compared to the PET group (P < .05), but reached equivalent values within 24-36 h postpartum. CO peaked at delivery of the newborn and the placenta and started to decline afterwards in both groups. The MAP and TPR values were significantly higher in the PET group at all points of assessment except at 48-72 h postpartum when it was still significantly higher for MAP while the TPR only exhibited a higher trend but not statistically significant. The NICaS™ device noninvasively demonstrated low CO and high TPR profiles in the PET group compared to controls. CONCLUSIONS: The immediate postpartum period is accompanied by the most dramatic hemodynamic changes and fluid shifts, during which the parturient should be closely monitored. The NICaS™ device may help the clinician to customize the most optimal management for individual parturients. Our findings require validation by further studies on larger samples.

The Hemodynamics of Labor in Women Undergoing Vaginal and Cesarean Deliveries as Determined by Whole Body Bioimpedance.

OBJECTIVE: The objective of this study was to assess the hemodynamics of labor, delivery, and 48 hours postpartum in women undergoing vaginal and cesarean deliveries by utilizing a whole body bioimpedance-based device. MATERIALS AND METHODS: A prospective longitudinal single-center observational study was performed between September 2014 and September 2015. The hemodynamics of low-risk women undergoing spontaneous vaginal delivery were compared with those undergoing elective cesarean sections. Cardiac index (CI), stroke index, total peripheral resistance index (TPRI), and mean arterial pressure (MAP) were assessed at different time points during delivery and in the immediate postpartum period (1, 24, and 48 hours postpartum). RESULTS: Eighty-seven women were evaluated, 63 parturients in the vaginal delivery group and 24 in the cesarean delivery group. Normal vaginal delivery was characterized by a reduction in MAP and CI after epidural anesthesia, whereas elective cesarean sections were characterized by a rise in MAP and CI after spinal anesthesia. As labor progressed, CI increased reaching its peak during the second stage. Immediately following delivery, TPRI declined to its nadir with no significant change in CI. As opposed to vaginal delivery, in cesarean delivery, TPRI peaked within 1-hour postpartum resulting in a significant decline in CI. CONCLUSION: Whole body bioimpedance can be used effectively to assess the hemodynamics of vaginal and cesarean deliveries.

Maternal hemodynamics in late gestation and immediate postpartum in singletons vs. twin pregnancies.

PURPOSE: Differences in hemodynamic changes during a cesarean section (CS) between twin and singleton pregnancies are poorly defined. The Non-Invasive Cardiac System (NICaS) is an impedance device that measures cardiac output (CO) and its derivatives. We compared maternal cardiac parameters using NICaS™ in singleton and twins before and during delivery, as well at the early puerperium in healthy women undergoing CS at term. METHODS: This prospective longitudinal study included women with twin (n = 27) or singleton pregnancies (n = 62) whose hemodynamic parameters were assessed by NICaS before an elective CS, after spinal anesthesia, immediately after delivery, after fascia closure, and within 24-36 and 48-72 h postpartum. RESULTS: By 24-36 h postpartum, the mean arterial pressure and the total peripheral resistance equaled preoperative values in both groups. The CO increased throughout the CS and peaked immediately after delivery in the singleton group (P < 0.0001), after which it abruptly began to decline until reaching a nadir 24-36 h after delivery (P < 0.0001), while it remained steady throughout the CS and then dropped until 24-36 h after delivery in the twin group (P < 0.05). None of the studied parameters differed significantly between the groups for the 24-36 and 48-72 h postpartum measurements. CONCLUSIONS: Hemodynamic parameters immediately before, during and shortly after CS in singleton and twin pregnancies are equivalent. Further evaluations of the value of NICaS™ in assessing cardiovascular-related pregnancy complications are warranted.

The utilization of solid organs for transplantation in the setting of infection with multidrug-resistant organisms: an expert opinion.

Organ transplantation remains the optimal treatment for many patients suffering from end-stage organ disease. Increasing numbers of patients admitted to intensive care units, among them potential heart-beating, brain-dead organ donors, are exposed to infections with multidrug-resistant organisms, in particular carbapenem-resistant Klebsiella pneumoniae (CR-KP). An extensive literature search failed to reveal any information regarding the eligibility for transplantation of organs from such donors. For this reason, in 2009, the Israel Transplant Center, together with the Israeli Society for Infectious Diseases, established a working group with the intention of developing a national-specific approach to the use of these organs. In this viewpoint article, we present an algorithm based on expert opinion and our clinical experience with a donor who was found to be an asymptomatic carrier of CR-KP.

Surfactant for the Treatment of ARDS in a Patient With COVID-19.

Patients with COVID-19 report severe respiratory symptoms consistent with ARDS. The clinical presentation of ARDS in COVID-19 is often atypical, as patients with COVID-19 exhibit a disproportionate hypoxemia compared with relatively preserved lung mechanics. This pattern is more similar to neonatal respiratory distress syndrome secondary to surfactant deficiency, which has been shown to benefit from exogenous surfactant. We present our experience with exogenous surfactant treatment in a patient with COVID-19 experiencing COVID-19-related ARDS. The patient responded with improved oxygenation, and we believe surfactant was the catalyst for the successful extubation and clinical improvement of the patient.

Enteral and supplemental parenteral nutrition enriched with omega-3 polyunsaturated fatty acids in intensive care patients - A randomized, controlled, double-blind clinical trial.

BACKGROUND & AIMS: Enteral nutrition (EN) and parenteral nutrition (PN) enriched with omega-3 polyunsaturated fatty acids (PUFA) have beneficial effects in critical illness. This study aimed to assess the combined effect of EN and supplemental PN enriched with omega-3 PUFA on blood oxygenation in intensive care unit (ICU) patients. METHODS: Single-center, prospective, randomized, controlled, double-blind, phase III trial conducted from 10/2013 to 11/2017. A total of 100 ICU patients (18-85 years, APACHE II score > 15) requiring mechanical ventilation were randomly assigned to received combined EN and PN either with omega-3 PUFA (omega-3 group) or without (control group) for up to 28 days. Primary endpoint: 'change of PaO2/FiO2 from day (D) 1 to D4'. Secondary endpoints: lung function parameters, ICU complications, length of hospital stay, days free of ICU care/ventilation/sedation/catecholamine treatment, mortality, erythrocyte fatty acid composition, inflammatory parameters. Safety parameters: standard laboratory assessment, vital signs, physical examination, SOFA score, adverse events. RESULTS: Combined EN and PN covered energy requirements to more than 80%. Blood oxygenation (ΔPaO2/FiO2 from D1 to D4: -1.3 ± 83.7, n = 42, and 13.3 ± 86.1, n = 39, in omega-3 and control group, respectively, p = 0.7795) and other lung function parameters did not differ between groups but days free of catecholamine treatment were significantly higher in the omega-3 group (~4 days, p = 0.0481). On D6, significantly more patients in the omega-3 group tolerated EN alone (51.0% vs. 29.8%, p = 0.0342). Eicosapentaenoic acid (EPA) content in erythrocytes was significantly increased in the omega-3 group at last observation compared with the control group (ΔEPA: 0.928 ± 0.808% vs. -0.024 ± 0.190%, p < 0.0001). No further significant group differences were detected. CONCLUSIONS: Enteral and supplemental PN both enriched with omega-3 PUFA did not improve lung function but allowed earlier weaning from catecholamine treatment and PN. Supplemental PN succeeded to adequately cover energy requirements in critically ill patients. TRIAL REGISTRATION: www.clinicaltrials.gov, registration number: NCT01162928.

Observational cohort study of IP-10's potential as a biomarker to aid in inflammation regulation within a clinical decision support protocol for patients with severe COVID-19.

BACKGROUND: Treatment of severely ill COVID-19 patients requires simultaneous management of oxygenation and inflammation without compromising viral clearance. While multiple tools are available to aid oxygenation, data supporting immune biomarkers for monitoring the host-pathogen interaction across disease stages and for titrating immunomodulatory therapy is lacking. METHODS: In this single-center cohort study, we used an immunoassay platform that enables rapid and quantitative measurement of interferon γ-induced protein 10 (IP-10), a host protein involved in lung injury from virus-induced hyperinflammation. A dynamic clinical decision support protocol was followed to manage patients infected with severe acute respiratory syndrome coronavirus 2 and examine the potential utility of timely and serial measurements of IP-10 as tool in regulating inflammation. RESULTS: Overall, 502 IP-10 measurements were performed on 52 patients between 7 April and 10 May 2020, with 12 patients admitted to the intensive care unit. IP-10 levels correlated with COVID-19 severity scores and admission to the intensive care unit. Among patients in the intensive care unit, the number of days with IP-10 levels exceeding 1,000 pg/mL was associated with mortality. Administration of corticosteroid immunomodulatory therapy decreased IP-10 levels significantly. Only two patients presented with subsequent IP-10 flare-ups exceeding 1,000 pg/mL and died of COVID-19-related complications. CONCLUSIONS: Serial and readily available IP-10 measurements potentially represent an actionable aid in managing inflammation in COVID-19 patients and therapeutic decision-making. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04389645, retrospectively registered on May 15, 2020.

BMI and pneumonia outcomes in critically ill covid-19 patients: An international multicenter study.

OBJECTIVE: Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID-19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID-19. METHODS: Patients admitted to intensive care units for COVID-19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28-day mortality, respectively. RESULTS: A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9-72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m2 (25.4-32.3); a total of 1,080 patients (73.9%) required IMV; and the 28-day mortality estimate was 36.1% (95% CI: 33.0-39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12-1.45) per 5 kg/m2 . An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06-2.64]). CONCLUSIONS: In critically ill COVID-19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed.

Effectiveness and safety of colistin: prospective comparative cohort study.

BACKGROUND: Colistin has re-entered clinical use by necessity. We aimed to assess its effectiveness and safety compared with newer antibiotics. METHODS: This was a single-centre, prospective cohort study. Inclusion criteria were microbiologically documented pneumonia, urinary tract infection, surgical site infection, meningitis or bacteraemia treated appropriately with colistin versus imipenem, meropenem or ampicillin/sulbactam (comparators). All consecutive patients were included, only once, between May 2006 and July 2009. The primary outcome was 30 day mortality. Multivariable and Cox regression survival analyses were used to adjust comparisons between groups. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals are reported. RESULTS: Two hundred patients treated with colistin and 295 patients treated with comparators were included. Treatment with colistin was associated with older age, admission from healthcare facilities, mechanical ventilation and lower rate of early appropriate antibiotic treatment. The 30 day mortality was 39% (78/200) for colistin versus 28.8% (85/295) for comparators; unadjusted OR 1.58 (1.08-2.31). In the adjusted analysis the OR was 1.44 (0.91-2.26) overall and 1.99 (1.06-3.77) for bacteraemic patients (n = 220). At the end of follow-up, treatment with colistin was significantly associated with cumulative mortality; adjusted HR 1.27 (1.01-1.60) overall and 1.65 (1.18-2.31) among patients with bacteraemia. Nephrotoxicity at the end of treatment was more frequent with colistin; OR adjusted for other risk factors for nephrotoxicity 3.31 (1.54-7.08). Treatment with colistin was followed by increased incidence of Proteus spp. infections during a 3 month follow-up. CONCLUSIONS: The need for colistin treatment is associated with poorer survival. Adjusted analyses suggest that colistin is less effective and more toxic than beta-lactam antibiotics.

Computerized lung acoustic monitoring can help to differentiate between various chest radiographic densities in critically ill patients.

BACKGROUND: Complementary bedside lung monitoring modalities are often sought in order to assist in the differentiation between several lung opacities in the intensive care unit (ICU). OBJECTIVES: To evaluate the use of computerized lung acoustic monitoring as a complementary approach in the differentiation between various chest radiographic densities in critically ill patients. METHODS: Lung vibration intensity was assessed in 82 intensive care patients using vibration response imaging. Patients were classified according to their primary findings on chest radiography (CXR): consolidation (n = 35), congestion (n = 10), pleural effusion (n = 15), atelectasis/hypoinflation (n = 10) and normal findings (n = 12). Sixty patients were mechanically ventilated and 22 patients were spontaneously breathing. RESULTS: Significantly elevated vibration intensity was detected in patients with consolidation, as opposed to pleural effusion, atelectasis and normal CXR (p < 0.01, Mann-Whitney U test). Vibration intensity was also increased for congestion, but this increase was not significant. The positive predictive value of CXR lung opacity in combination with increased vibration intensity to detect consolidations and/or congestions was 95% (20/21). Furthermore, vibration intensity was significantly higher in mechanically ventilated patients compared to spontaneously breathing patients (p = 0.001, Mann-Whitney U test). Differences related to gender, age and body position were not significant. CONCLUSIONS: Computerized lung acoustic monitoring at the bedside was found to be a useful, readily available, noninvasive, adjunctive tool in the differentiation between various CXR densities in critically ill patients.

A Time Frame for Testing Negative for SARS-COV2 in People with Obesity.

OBJECTIVE: Obesity is a major risk factor for becoming seriously ill with the 2019 novel coronavirus (COVID-19). One difficulty faced by clinicians and by patients is the unknown time frame of hospitalization until discharge of symptomatic patients. METHODS: We followed 34 patients with laboratory-confirmed COVID-19 infection who recovered fromthe infection. All diagnoses were given using semi-quantitative RT-PCR on nasopharyngeal swabs. Envelope protein gene (E), RNA-dependent RNA polymerase gene (RdRP), and nucleocapsid gene (N) were measured by RT-PCR. Weight was measured and height was self-reported. RESULTS: Mean ± SD age was 51.8 ± 16.7 years. Mean ± SD body mass index (BMI) was 27.4 ± 4.7 kg/m2. 26% (9/34) had obesity, with BMI above 30 kg/m2. Fifteen patients had BMI between 25 and 29.9 kg/m2. The mean length of hospital stay was longer for those with a BMI >25 kg/m2 (n = 24) than for those with a normal BMI (19.2 vs. 16.0 days, p = 0.08). Comparing people with obesity (BMI >30 kg/m2 or above) to those without obesity, the difference was larger (20.6 vs. 16.0 days, p = 0.06). A trend for correlation between body weight and the time to negative detection of RdRp gene was found (r = 0.33, p = 0.09). CONCLUSIONS: Our results highlight the need for priority of early detection and testing, and early therapy for people with obesity and COVID-19 infections.

Clinical Course and Outcomes of Severe Covid-19: A National Scale Study.

Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined. METHODS: This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020. Demographic and clinical data including clinical management were collected and subjected to a multivariable analysis; primary outcome was mortality. RESULTS: This study included 156 patients (median age = 72 years (range = 22-97 years)); 69% (108 of 156) were male. Eighty-nine percent (139 of 156) of patients had at least one comorbidity. One hundred three patients (66%) required invasive mechanical ventilation. As of 8 May 2020, the median length of stay in the ICU was 10 days (range = 0-37 days). The overall mortality rate was 56%; a multivariable regression model revealed that increasing age (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), the presence of sepsis (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), and a shorter ICU stay(OR = 0.90 for each day, 95% CI = 0.84-0.96) were independent prognostic factors. CONCLUSIONS: In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.

Prediction of extubation outcome: a randomised, controlled trial with automatic tube compensation vs. pressure support ventilation.

INTRODUCTION: Tolerance of a spontaneous breathing trial is an evidence-based strategy to predict successful weaning from mechanical ventilation. Some patients may not tolerate the trial because of the respiratory load imposed by the endotracheal tube, so varying levels of respiratory support are widely used during the trial. Automatic tube compensation (ATC), specifically developed to overcome the imposed work of breathing because of artificial airways, appears ideally suited for the weaning process. We further evaluated the use of ATC in this setting. METHODS: In a prospective study, patients who had received mechanical ventilation for more than 24 hours and met defined criteria for a weaning trial, underwent a one-hour spontaneous breathing trial with either ATC (n = 87) or pressure support ventilation (PSV; n = 93). Those tolerating the trial were immediately extubated. The primary outcome measure was the ability to maintain spontaneous, unassisted breathing for more than 48 hours after extubation. In addition, we measured the frequency/tidal volume ratio (f/VT) both with (ATC-assisted) and without ATC (unassisted-f/VT) at the start of the breathing trial as a pretrial predictor of extubation outcome. RESULTS: There were no significant differences in any of the baseline characteristics between the two groups apart from a significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score in the ATC group (p = 0.009). In the PSV group, 13 of 93 (14%) patients failed the breathing trial compared with only 6 of 87 (6%) in the ATC group; this observed 8% difference, however, did not reach statistical significance (p = 0.12). The rate of reintubation was not different between the groups (total group = 17.3%; ATC = 18.4% vs. PSV = 12.9%, p = 0.43). The percentage of patients who remained extubated for more than 48 hours was similar in both groups (ATC = 74.7% vs. PSV = 73.1%; p = 0.81). This represented a positive predictive value for PSV of 0.85 and ATC of 0.80 (p = 0.87). Finally, the ATC-assisted f/VT was found to have a significant contribution in predicting successful liberation and extubation compared with the non-significant contribution of the unassisted f/VT (unassisted f/VT, p = 0.19; ATC-assisted f/VT, p = 0.005). CONCLUSIONS: This study confirms the usefulness of ATC during the weaning process, being at least as effective as PSV in predicting successful extubation outcome and significantly improving the predictive value of the f/VT. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16080446.

Changes in regional distribution of lung sounds as a function of positive end-expiratory pressure.

INTRODUCTION: Automated mapping of lung sound distribution is a novel area of interest currently investigated in mechanically ventilated, critically ill patients. The objective of the present study was to assess changes in thoracic sound distribution resulting from changes in positive end-expiratory pressure (PEEP). Repeatability of automated lung sound measurements was also evaluated. METHODS: Regional lung sound distribution was assessed in 35 mechanically ventilated patients in the intensive care unit (ICU). A total of 201 vibration response imaging (VRI) measurements were collected at different levels of PEEP between 0 and 15 cmH2O. Findings were correlated with tidal volume, oxygen saturation, airway resistance, and dynamic compliance. Eighty-two duplicated readings were performed to evaluate the repeatability of the measurement. RESULTS: A significant shift in sound distribution from the apical to the diaphragmatic lung areas was recorded when increasing PEEP (paired t-tests, P < 0.05). In patients with unilateral lung pathology, this shift was significant in the diseased lung, but not as pronounced in the other lung. No significant difference in lung sound distribution was encountered based on level of ventilator support needed. Decreased lung sound distribution in the base was correlated with lower dynamic compliance. No significant difference was encountered between repeated measurements. CONCLUSIONS: Lung sounds shift towards the diaphragmatic lung areas when PEEP increases. Lung sound measurements are highly repeatable in mechanically ventilated patients with various lung pathologies. Further studies are needed in order to fully appreciate the contribution of PEEP increase to diaphragmatic sound redistribution.