The potential impact and diagnostic value of inflammatory markers on diabetic foot progression in type II diabetes mellitus: A case-control study.

BACKGROUND: The wound-healing process in diabetic foot is affected by pro and anti-inflammatory markers, and any disruption in the inflammatory reaction interferes with tissue homeostasis, leading to chronic non-wound healing. AIM: This study aimed to determine the diagnostic value and effect of CRP, IL-6, TNF, and HbA1c on initiation the and progression of diabetic foot ulcers. METHOD: ELISA was used to quantify IL-6, TNF, CRP, and HbA1c in 205 patients with diabetes, and 105 were diabetic foot free. The prevalence and progression of diabetic foot were also evaluated. The area under the curve (AUC) was calculated using the receiver operating characteristic (ROC) curve to analyze the predictive values. Forward stepwise logistic regression analysis was used to compute the odds ratio (OR) and the corresponding 95% confidence intervals (CIs). RESULTS: CRP, IL-6, and FBS were found to be significant predictors of diabetic foot (OR=1.717, 95% CI=1.250-2.358, P=0.001; OR=1.434, 95% CI=1.142-1.802, P=0.002; and OR=1.040, 95% CI=1.002-1.080, P=0.037), respectively. The AUCs for CRP, IL-6, and HbA1c in predicting diabetic foot were 0.839, 0.728, and 0.834, respectively, demonstrating a good predictive value for each diagnostic marker. CONCLUSION: The current study demonstrated that IL-6, CRP, and HbA1c may be useful biomarkers to indicate diabetic foot progression. Furthermore, our findings showed a substantial relationship between CRP and HbA1c in individuals with diabetic foot conditions.

Association of rs1544410 and rs7975232 Polymorphisms and Serum Vitamin D Levels with Psoriasis Susceptibility and Severity: A Case-Control Study in Egyptian Patients.

Background: Vitamin D is a regulatory factor for skin immune functions through vitamin D receptor, which is expressed on many immune cells. Vitamin D receptor is located on chromosome 12q 13.11 and has many single nucleotide polymorphisms. Some of them were hypothesized to be associated with psoriasis. Psoriasis is a genetic disease that is greatly affected by environmental factors. Methods: A total of 135 psoriasis patients and 114 healthy controls were recruited. Both had a measurement of serum vitamin D and two vitamin D receptor variants:, rs1544410: G > A (HGVS:NC_000012.12:g.47846052) and rs7975232: C > A (HGVS: NC_000012.12:g.47845054). We assessed the relationship between vitamin deficiency as well as the two gene polymorphisms with psoriasis susceptibility and severity. Results: Serum vitamin D levels were not significantly different between cases and controls. However, a significant association between vitamin D levels and severity was observed. We attributed this to our finding that rs7975232 was more significantly polymorphic among cases than controls, while rs1544410 polymorphism did not show a significant difference among the 2 groups. Conclusion: We did not find a significant difference in serum vitamin D levels between cases and controls. Yet, psoriasis severity was significantly associated with serum vitamin D levels. We attributed this to other findings that the vitamin D receptor rs7975232 gene is polymorphic in psoriasis patients. At the same time, rs1544410 was not significantly more polymorphic in psoriasis patients. Both genes' polymorphisms were associated with severe psoriasis.

Selepressin in Septic Shock.

ABSTRACT: Sepsis and septic shock usually show a high mortality rate and frequently need of intensive care unit admissions. After fluid resuscitation, norepinephrine (NE) is the first-choice vasopressor in septic shock patients. However, high-NE doses are associated with increased rates of adverse effects and mortality. In this perspective, many authors have proposed the administration of non-adrenergic vasopressors (NAV). Selepressin is a selective vasopressin type 1A (V1A) receptor agonist and may be a valid option in this field, because it can decrease NE requirements and also limit the deleterious effects induced by high doses of catecholamines. Only few clinical data actually support selepressin administration in this setting. Here, we review the current literature on this topic analyzing some pathophysiological aspects, the rationale about the use of NAV, the possible use of selepressin differentiating animal, and human studies. Various issues remain unresolved and future trials should be focused on early interventions based on a multimodal activation of the vasopressive pathways using both alpha and V1A receptors pathways.

Evaluation of Expressed MicroRNAs as Prospective Biomarkers for Detection of Breast Cancer.

Background: Early detection and screening of breast cancer (BC) might help improve the prognosis of BC patients. This study evaluated the use of serum microRNAs (miRs) as non-invasive biomarkers in BC patients. Methods: Using quantitative real-time polymerase chain reaction, we evaluated the serum expression of four candidate miRs (miR-155, miR-373, miR-10b, and miR-34a) in 99 Egyptian BC patients and 40 healthy subjects (as a control). The miRs expression was correlated with clinicopathological data. In addition, the sensitivity and specificity of the miRs were determined using receiver operating characteristic (ROC) curve analysis. Results: Serum miR-155, miR-373, and miR-10b expression were significantly upregulated (p < 0.001), while serum miR-34a was downregulated (p < 0.00) in nonmetastatic (M0) BC patients compared to the control group. In addition, serum miR-155 and miR-10b were upregulated in BC patients with large tumor sizes and extensive nodal involvement (p < 0.001). ROC curve analysis showed high diagnostic accuracy (area under the curve = 1.0) when the four miRs were combined. Serum miR-373 was significantly upregulated in the human epidermal growth factor 2−negative (p < 0.001), estrogen receptor−positive (p < 0.005), and progesterone receptor (PR)-positive (p < 0.024) in BC patients, and serum miR-155 was significantly upregulated in PR-negative (p < 0.001) BC patients while both serum miR-155 and miR-373 were positively correlated with the tumor grade. Conclusions: Circulating serum miR-155, miR-373, miR-10b, and miR-34a are potential biomarkers for early BC detection in Egyptian patients and their combination shows high sensitivity and specificity.

Perspectives of patients, family members, health professionals and the public on the impact of COVID-19 on mental health.

BACKGROUND: The coronavirus (COVID-19) pandemic has seen a global surge in anxiety, depression, post-traumatic stress disorder (PTSD), and stress. AIMS: This study aimed to describe the perspectives of patients with COVID-19, their family, health professionals, and the general public on the impact of COVID-19 on mental health. METHODS: A secondary thematic analysis was conducted using data from the COVID-19 COS project. We extracted data on the perceived causes and impact of COVID-19 on mental health from an international survey and seven online consensus workshops. RESULTS: We identified four themes (with subthemes in parenthesis): anxiety amidst uncertainty (always on high alert, ebb and flow of recovery); anguish of a threatened future (intense frustration of a changed normality, facing loss of livelihood, trauma of ventilation, a troubling prognosis, confronting death); bearing responsibility for transmission (fear of spreading COVID-19 in public; overwhelming guilt of infecting a loved one); and suffering in isolation (severe solitude of quarantine, sick and alone, separation exacerbating grief). CONCLUSION: We found that the unpredictability of COVID-19, the fear of long-term health consequences, burden of guilt, and suffering in isolation profoundly impacted mental health. Clinical and public health interventions are needed to manage the psychological consequences arising from this pandemic.

Correlation of quantitative computed tomography derived bone density values with Hounsfield units of a contrast medium computed tomography in 98 thoraco-lumbar vertebral bodies.

INTRODUCTION: Vertebral fractures in patients with bone density reduction are often a major challenge for the surgeon, as reduced bone density can lead to screw loosening. Several options are available to determine bone density preoperatively. In our study, we investigated the correlation of Hounsfield units (HU) of a contrast medium computed tomography (CT) to the bone density values of a quantitative computed tomography (QCT) and computed a formula to estimate bone density values using HU. MATERIALS AND METHODS: In our retrospective data analysis, we examine 98 vertebral bodies from 35 patients who received a contrast medium CT of the spine and a QCT, performed no longer than 1 month apart. The determined HU from the contrast medium CT were compared with the bone density values of the QCT and examined for correlations. Linear logistic regression was used to estimate bone density values base on HU. RESULTS: A strong correlation was found between the HU measured in the CT and the bone density values (r = 0.894, p < 0.001), irrespective of patients' gender. We also found no correlation differences when the HU were measured at different levels. Bland-Altman plot demonstrated good agreement between the two measurements. The following formula was developed to estimate bone density values using HU: QCT-value = 0.71 × HU + 13.82. CONCLUSIONS: Bone density values correlate well to HU measured in contrast medium CT. Using simple formula, the bone density of a contrast medium CT of vertebral bodies can be estimated based on HU without additional examinations and unnecessary costs.

Characteristics and outcome of critically ill patients with coronavirus disease-2019 (COVID-19) pneumonia admitted to a tertiary care center in the United Arab Emirates during the first wave of the SARS-CoV-2 pandemic. A retrospective analysis.

BACKGROUND: The aim of this study was to describe the clinical characteristics and outcome of patients with coronavirus disease-2019 (COVID-19) pneumonia admitted to an intensive care unit (ICU) of a tertiary care center in the United Arab Emirates (UAE) and to identify early risk factors for in-hospital mortality in these patients. METHODS: A total of 371 adult patients (>18 years) admitted to the ICU of Al Ain Hospital between March 16 and July 19, 2020 with SARS-CoV-2 infection confirmed using real-time reverse transcription polymerase chain reaction (rt-PCR) on nasopharyngeal swabs were included. RESULTS: The mean patient age was 53 years (standard deviation = 13). Patients were mostly male (n = 314 [84.6%]) and of South Asian origin (n = 231 [62.3%]). Invasive mechanical ventilation was required in 182 (49.1%) patients for a median of 11 days (25-75% interquartile range: 6-17). During the ICU stay, renal replacement therapy was required in 87 (23.5%) and vasopressor therapy in 190 (51.2%) patients. ICU and hospital lengths of stay were 9 (IQ: 5-17) and 18 (IQ: 13-29) days, respectively and ICU and hospital mortality rates were both 20.2%. In a multivariable analysis with in-hospital mortality as the dependent variable, greater Acute Physiology and Chronic Health Evaluation II score on ICU admission, diarrhea prior to hospital admission, greater, admission from hospital ward, and higher lactate dehydrogenase levels and neutrophil:lymphocyte ratio on admission to the ICU were independently associated with higher risk of in-hospital mortality. CONCLUSION: In this cohort of patients admitted to the ICU of a tertiary hospital in the UAE, COVID-19 pneumonia was associated with high morbidity and mortality rates. Identifying patients at high risk of death may help detect future therapeutic targets.

Do ventilatory parameters influence outcome in patients with severe acute respiratory infection? Secondary analysis of an international, multicentre14-day inception cohort study.

PURPOSE: To investigate the possible association between ventilatory settings on the first day of invasive mechanical ventilation (IMV) and mortality in patients admitted to the intensive care unit (ICU) with severe acute respiratory infection (SARI). MATERIALS AND METHODS: In this pre-planned sub-study of a prospective, multicentre observational study, 441 patients with SARI who received controlled IMV during the ICU stay were included in the analysis. RESULTS: ICU and hospital mortality rates were 23.1 and 28.1%, respectively. In multivariable analysis, tidal volume and respiratory rate on the first day of IMV were not associated with an increased risk of death; however, higher driving pressure (DP: odds ratio (OR) 1.05; 95% confidence interval (CI): 1.01-1.1, p = 0.011), plateau pressure (Pplat) (OR 1.08; 95% CI: 1.04-1.13, p < 0.001) and positive end-expiratory pressure (PEEP) (OR 1.13; 95% CI: 1.03-1.24, p = 0.006) were independently associated with in-hospital mortality. In subgroup analysis, in hypoxemic patients and in patients with acute respiratory distress syndrome (ARDS), higher DP, Pplat, and PEEP were associated with increased risk of in-hospital death. CONCLUSIONS: In patients with SARI receiving IMV, higher DP, Pplat and PEEP, and not tidal volume, were associated with a higher risk of in-hospital death, especially in those with hypoxemia or ARDS.

Outcomes and risk factors for death in patients with coronavirus disease-2019 (COVID-19) pneumonia admitted to the intensive care units of an Egyptian University Hospital. A retrospective cohort study.

BACKGROUND: The characteristics, outcomes, and risk factors for in-hospital death of critically ill intensive care unit (ICU) patients with coronavirus disease-2019 (COVID-19) have been described in patients from Europe, North America and China, but there are few data from COVID-19 patients in Middle Eastern countries. The aim of this study was to investigate the characteristics, outcomes, and risk factors for in-hospital death of critically ill patients with COVID-19 pneumonia admitted to the ICUs of a University Hospital in Egypt. METHODS: Retrospective analysis of patients with COVID-19 pneumonia admitted between April 28 and July 29, 2020 to two ICUs dedicated to the isolation and treatment of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Cairo University Hospitals. Diagnosis was confirmed in all patients using real-time reverse transcription polymerase chain reaction on respiratory samples and radiologic evidence of pneumonia. RESULTS: Of the 177 patients admitted to the ICUs during the study period, 160 patients had COVID-19 pneumonia and were included in the analysis (mean age: 60 ± 14 years, 67.5% males); 23% of patients had no known comorbidities. The overall ICU and hospital mortality rates were both 24.4%. The ICU and hospital lengths of stay were 7 (25-75% interquartile range: 4-10) and 10 (25-75% interquartile range: 7-14) days, respectively. In a multivariable analysis with in-hospital death as the dependent variable, ischemic heart disease, history of smoking, and secondary bacterial pneumonia were independently associated with a higher risk of in-hospital death, whereas greater PaO2/FiO2 ratio on admission to the ICU was associated with a lower risk. CONCLUSION: In this cohort of critically ill patients with COVID-19 pneumonia, ischemic heart disease, history of smoking, and secondary bacterial pneumonia were independently associated with a higher risk of in-hospital death.

Correlation of Bone Density Values of Quantitative Computed Tomography and Hounsfield Units Measured in Native Computed Tomography in 902 Vertebral Bodies.

OBJECTIVE: Due to the increasing age of patients, the evaluation of bone density is crucial, especially in preparation for spinal surgery. The aim of this study was to determine bone density using a computed tomography (CT) and to correlate Hounsfield units (HU) with bone density values of a quantitative computed tomography (QCT). METHODS: The study is a monocentric, retrospective data analysis. We examined 902 vertebral bodies from a total of 369 patients who received a CT of the thoracolumbar spine in the period from 2015 to 2019 and compared the HU with values of a QCT. A general equation for calculation the QCT values was established. RESULTS: We found a significant correlation between the Hounsfield units and the corresponding QCT-values (r = 0.944, P < 0.001). We also demonstrated that the calculated QCT values are independent of patient sex (P < 0.942). Furthermore, we could not demonstrate differences in the correlation of the 3 measured levels (axial, sagittal, and coronary) to the QCT values. The QCT-values can be calculated on the basis of a native CT of the lumbar spine using the equation: QCT = 17.8 + 0.7 × HU. CONCLUSIONS: The equation allows calculating bone density values without the need for an additional QCT and without further radiation exposure or costs. With this measuring method it is possible to obtain additional information from a computed tomography.

A biomechanical comparison of a cement-augmented odontoid screw with a posterior-instrumented fusion in geriatric patients with an odontoid fracture type IIb.

PURPOSE: Possible surgical therapies for odontoid fracture type IIb include odontoid screw osteosynthesis (OG) with preservation of mobility or dorsal C1/2 fusion with restriction of cervical rotation. In order to reduce material loosening in odontoid screw osteosynthesis in patients with low bone density, augmentation at the base of the axis using bone cement has been established as a suitable alternative. In this study, we compared cement-augmented OG and C1/2 fusion according to Harms (HG). METHODS: Body donor preparations of the 1st and 2nd cervical vertebrae were randomized in 2 groups (OG vs. HG). The range of motion (ROM) was determined in 3 principle motion plains. Subsequently, a cyclic loading test was performed. The decrease in height of the specimen and the double amplitude height were determined as absolute values as an indication of screw loosening. Afterward, the ROM was determined again and loosening of the screws was measured in a computed tomography. RESULTS: A total of 16 were included. Two groups of 8 specimens (OG vs. HG) from patients with a median age of 80 (interquartile range (IQ) 73.5-85) years and a reduced bone density of 87.2 (IQ 71.2-104.5) mg/cc dipotassium hydrogen phosphate were examined for their biomechanical properties. Before and after exposure, the OG preparations were significantly more mobile. At the time of loading, the OG had similar loading properties to HG decrease in height of the specimen and the double amplitude height. Computed tomography revealed similar outcomes with regard to the screw loosening rate (62.5 vs. 87.5%, p = 0.586). CONCLUSION: In patients with an odontoid fracture type IIb and reduced bone density, cement-augmented odontoid screw yielded similar properties in the loading tests compared to the HG. It may, therefore, be considered as a primary alternative to preserve cervical mobility in these patients.

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts.

BACKGROUND: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. METHODS: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1-15, 2002 (SOAP study, n = 3147), and May 8-18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. RESULTS: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1-7) days after admission in SOAP and 2 (1-6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. CONCLUSION: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies.

Current use of inotropes in circulatory shock.

BACKGROUND: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. METHODS: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. RESULTS: A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81-90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). CONCLUSION: Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.

Core Outcome Measures for Trials in People With Coronavirus Disease 2019: Respiratory Failure, Multiorgan Failure, Shortness of Breath, and Recovery.

OBJECTIVES: Respiratory failure, multiple organ failure, shortness of breath, recovery, and mortality have been identified as critically important core outcomes by more than 9300 patients, health professionals, and the public from 111 countries in the global coronavirus disease 2019 core outcome set initiative. The aim of this project was to establish the core outcome measures for these domains for trials in coronavirus disease 2019. DESIGN: Three online consensus workshops were convened to establish outcome measures for the four core domains of respiratory failure, multiple organ failure, shortness of breath, and recovery. SETTING: International. PATIENTS: About 130 participants (patients, public, and health professionals) from 17 countries attended the three workshops. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Respiratory failure, assessed by the need for respiratory support based on the World Health Organization Clinical Progression Scale, was considered pragmatic, objective, and with broad applicability to various clinical scenarios. The Sequential Organ Failure Assessment was recommended for multiple organ failure, because it was routinely used in trials and clinical care, well validated, and feasible. The Modified Medical Research Council measure for shortness of breath, with minor adaptations (recall period of 24 hr to capture daily fluctuations and inclusion of activities to ensure relevance and to capture the extreme severity of shortness of breath in people with coronavirus disease 2019), was regarded as fit for purpose for this indication. The recovery measure was developed de novo and defined as the absence of symptoms, resumption of usual daily activities, and return to the previous state of health prior to the illness, using a 5-point Likert scale, and was endorsed. CONCLUSIONS: The coronavirus disease 2019 core outcome set recommended core outcome measures have content validity and are considered the most feasible and acceptable among existing measures. Implementation of the core outcome measures in trials in coronavirus disease 2019 will ensure consistency and relevance of the evidence to inform decision-making and care of patients with coronavirus disease 2019.

The clinical spectrum of pulmonary thromboembolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: A European case series.

PURPOSE: To describe the clinical characteristics and outcomes of coronavirus disease-2019 (COVID-19)-associated pulmonary thromboembolism (PTE). MATERIALS AND METHODS: A case series of five patients, representing the clinical spectrum of COVID-19 associated PTE. Patients were admitted to four hospitals in Germany, Italy, and France. Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was confirmed using a real-time reverse transcription polymerase chain reaction test. RESULTS: The onset of PTE varied from 2 to 4 weeks after the occurrence of the initial symptoms of SARS-CoV-2 infection and led to deterioration of the clinical picture in all cases. PTE was the primary reason for hospital admission after a 2-week period of self-isolation at home (1 patient) and hospital readmission after initial uncomplicated hospital discharge (2 patients). Three of the patients had no past history of clinically relevant risk factors for venous thromboembolism (VTE). Severe disease progression was associated with concomitant increases in IL-6, ferritin, and D-Dimer levels. The outcome from PTE was related to the extent of vascular involvement, and associated complications. CONCLUSION: PTE is a potential life-threatening complication, which occurs frequently in patients with COVID-19. Intermediate therapeutic dose of anticoagulants and extend thromboprophylaxis are necessary after meticulous risk-benefit assessment.

Randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS): protocol for a randomized controlled trial.

BACKGROUND: Albumin is a key regulator of fluid distribution within the extracellular space and has several properties beyond its oncotic activity. The accumulating evidence suggests that supplementation of albumin may provide survival advantages only when the insult is severe as in patients with septic shock. METHODS/DESIGN: The randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS) investigates whether the replacement with albumin and the maintenance of its serum levels of at least 30 g/l for 28 days improve survival in patients with septic shock compared to resuscitation and volume maintenance without albumin. Adult patients (≥ 18 years) with septic shock are randomly assigned within a maximum of 24 h after the onset of septic shock after obtaining informed consents to treatment or control groups. Patients assigned to the treatment group receive a 60-g loading dose of human albumin 20% over 2-3 h. Serum albumin levels are maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion. The control group is treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. The primary endpoint is 90 days mortality and secondary endpoints include 28-day, 60-day, ICU, and in-hospital mortality, organ dysfunction/failure, total amount of fluid administration and total fluid balance in the ICU, and lengths of ICU and hospital stay. In total, 1412 patients need to be analysed, 706 per group. For the sample size estimation, a 15% reduction in 90-day mortality is assumed, i.e. an absolute reduction of 7.5% points to 42.5% (relative risk 1.18). Assuming a dropout rate of 15%, a total of 1662 patients need to be allocated. DISCUSSION: The results of the clinical trial may influence the treatment of patients with septic shock. The expected improvement in patient survival may result in a reduction in the resources currently used in the treatment of these patients and in the socioeconomic burden of this disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03869385 . Registration on 18 July 2019. Protocol version: Final 3.0.

Pulmonary embolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: a narrative review.

BACKGROUND: Preliminary reports have described significant procoagulant events in patients with coronavirus disease-2019 (COVID-19), including life-threatening pulmonary embolism (PE). MAIN TEXT: We review the current data on the epidemiology, the possible underlying pathophysiologic mechanisms, and the therapeutic implications of PE in relation to COVID-19. The incidence of PE is reported to be around 2.6-8.9% of COVID-19 in hospitalized patients and up to one-third of those requiring intensive care unit (ICU) admission, despite standard prophylactic anticoagulation. This may be explained by direct and indirect pathologic consequences of COVID-19, complement activation, cytokine release, endothelial dysfunction, and interactions between different types of blood cells. CONCLUSION: Thromboprophylaxis should be started in all patients with suspected or confirmed COVID-19 admitted to the hospital. The use of an intermediate therapeutic dose of low molecular weight (LMWH) or unfractionated heparin can be considered on an individual basis in patients with multiple risk factors for venous thromboembolism, including critically ill patients admitted to the ICU. Decisions about extending prophylaxis with LMWH after hospital discharge should be made after balancing the reduced risk of venous thromboembolism (VTE) with the risk of increased bleeding events and should be continued for 7-14 days after hospital discharge or in the pre-hospital phase in case of pre-existing or persisting VTE risk factors. Therapeutic anticoagulation is the cornerstone in the management of patients with PE. Selection of an appropriate agent and correct dosing requires consideration of underlying comorbidities.

International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019.

OBJECTIVES: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials. DESIGN: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically. SETTING: International. SUBJECTS: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers). INTERVENTIONS: None. MEASUREMENTS: None. MAIN RESULTS: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. CONCLUSIONS: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.