International Multicenter Observational Study Research Articles

Practice of Fluid and Vasopressor Therapy in Critically Ill Invasively Ventilated Patients (PRoFLUID)—study protocol for an international multicenter observational cohort study

Practice of Fluid and Vasopressor Therapy in Critically Ill Invasively Ventilated Patients (PRoFLUID)—study protocol for an international multicenter observational cohort study

Development and validation of a novel predictive model for postpancreatectomy hemorrhage using lasso-logistic regression: an international multicenter observational study of 9,631 pancreatectomy patients.

Hemorrhage following pancreatectomy represents a grave complication, exerting a significant impact on patient prognosis. The formulation of a precise predictive model for postpancreatectomy hemorrhage risk holds substantial importance in enhancing surgical safety and improving patient outcomes. This study utilized the patient cohort from the American College of Surgeons National Surgical Quality Improvement Program database, who underwent pancreatectomy between 2014 and 2017 (n=5779), as the training set to establish the Lasso-logistic model. For external validation, a patient cohort (n=3852) from the Chinese National Multicenter Database of Pancreatectomy Patients, who underwent the procedure between 2014 and 2020, was employed. A predictive nomogram for postpancreatectomy hemorrhage was developed, and polynomial equations were extracted. The performance of the predictive model was assessed through the receiver operating characteristic curve, calibration curve, and decision curve analysis. In the training and validation cohorts, 9.0% (520/5779) and 8.5% (328/3852) of patients, respectively, experienced postpancreatectomy hemorrhage. Following selection via lasso and logistic regression, only nine predictive factors were identified as independent risk factors associated with postpancreatectomy hemorrhage. These included five preoperative indicators (BMI, ASA ≥3, preoperative obstructive jaundice, chemotherapy within 90 days before surgery, and radiotherapy within 90 days before surgery), two intraoperative indicators (total operation time, vascular resection), and two postoperative indicators (postoperative septic shock, pancreatic fistula). The new model demonstrated high predictive accuracy, with an area under the receiver operating characteristic curve of 0.87 in the external validation cohort. Its predictive performance significantly surpassed that of the previous five postpancreatectomy hemorrhage risk prediction models (P<0.001, likelihood ratio test). The Lasso-logistic predictive model we developed, constructed from nine rigorously selected variables, accurately predicts the risk of PPH. It has the potential to significantly enhance the safety of pancreatectomy surgeries and improve patient outcomes.

Nodular number as a prognostic indicator in hepatic resection for intermediate-stage hepatocellular carcinoma: An international multicenter observational study.

e16271 Background: The role of hepatic resection in treating Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) is a subject of ongoing debate. This study aims to assess the prognostic significance of the number of nodular HCC in patients undergoing hepatic resection for intermediate-stage (BCLC stage B) HCC. Methods: An analysis was conducted using data from a multicenter database of patients who underwent curative-intent resection for BCLC intermediate-stage HCC. Patients were classified into binodular and tri(+)nodular (≥ 3 nodules) groups based on the number of tumor nodules. Long-term overall survival (OS) and recurrence-free survival (RFS) were compared between these groups. Univariate and multivariate Cox-regression analyses identified risk factors for OS and RFS. Additional comparisons were made with outcomes in patients with uninodular large HCC (single nodule &gt; 5 cm; BCLC stage A). Results: Of the 338 patients with BCLC intermediate-stage HCC, 187 (55.3%) had binodular and 151 (44.7%) had tri(+)nodular disease. Patients with binodular HCC showed significantly better median OS (49.6 months) and RFS (22.2 months) compared to those with tri(+)nodular HCC (33.5 and 13.7 months, P = 0.036 and 0.009, respectively), and outcomes comparable to those with uninodular large HCC (59.8 and 26.8 months, P = 0.144 and 0.311, respectively). Multivariate analyses indicated that binodular HCC was independently associated with improved OS and RFS following hepatic resection in BCLC intermediate-stage HCC. Conclusions: Patients with binodular HCC exhibit more favorable survival outcomes post-resection of BCLC intermediate-stage HCC compared to those with tri(+)nodular HCC, akin to outcomes observed in BCLC early-stage uninodular large HCC. These findings highlight the prognostic relevance of nodular number in stratifying and guiding surgical decisions for intermediate-stage HCC. [Table: see text]

Local Excision for organ preservation in early REctal cancer with No Adjuvant treatment (LORENA Trial): prospective observational study protocol

IntroductionLocal resection (LR) is an alternative to total mesorectal excision (TME) that avoids its associated morbidity to the detriment of oncological radicality in early stages of rectal cancer. There are several conditioning factors for the success of this strategy, such as poor prognosis histological factors (PPHF), involvement of resection margins, clinical under staging, or complications that may lead to the indication for radical surgery with TME. Patients and methodAn international multicenter prospective observational open-label study has been designed. Consecutive patients diagnosed with early rectal cancer (cT1N0 on MRI +/− endorectal ultrasound) whose lower limit is a maximum of 2 cm proximal to the ano-rectal junction will be included. The primary objective of the study is to determine the overall prevalence of PPHF after LR and requiring TME or postoperative radio-chemotherapy. DiscussionThe prevalence of PPHF conditioning the success of LR in early distal rectal cancer has been scarcely studied in the literature, and there are very few prospective data. Considering the increasing interest in the watch and wait strategy in rectal cancer and its possible application in early-stage tumors, it seems necessary to know this information.The results of this study will help guide clinical practice in patients with early distal rectal cancer. It will also provide quality information for the design of future comparative studies to improve organ preservation success in these patients.Trial registration number: NCT05927584.

Let's Agree to Disagree on Operative Versus Nonoperative Treatment for Distal Radius Fractures in Older People: Protocol for a Prospective International Multicenter Cohort Study.

Distal radius fractures are the most frequently encountered fractures in Western societies, typically affecting patients aged 50 years and older. Although this is a common injury, the best treatment for these fractures in older patients is still under debate. This prospective study aims to compare the outcome of operatively and nonoperatively treated distal radius fractures in the older population. Only patients with distal radius fractures for which equipoise regarding the optimal treatment exists will be included. This prospective international multicenter observational cohort study will be designed as a natural experiment. Natural experiments are observational studies in which treatment allocation is determined by factors outside the control of the investigators but also (largely) independent of patient characteristics. Patients aged 65 years and older with an acute distal radius fracture will be considered for inclusion. Treatment allocation (operative vs nonoperative) will be based on the local preferences of the treating hospital either in Switzerland or the Netherlands. Hence, the process governing treatment allocation resembles that of randomization. Patients will be identified after treatment has been initiated. Based on the radiographs and baseline information of the patient, an expert panel of 6 certified trauma surgeons from 2 regions will provide their treatment recommendation. Only patients for whom the experts disagree on treatment recommendations will ultimately be included in the study (ie, for whom there is a clinical equipoise). For these patients, both operative and nonoperative treatment of distal radius fractures are viable, and treatment choice is predominantly determined by personal or local preference. The primary outcome will be the Patient-Rated Wrist Evaluation score at 12 weeks. Secondary outcomes will include the Physical Activity Score for the Elderly, the EQ questionnaire, pain, the living situation, range of motion, complications, and radiological outcomes. By including outcomes such as living situation and the Physical Activity Score for the Elderly, which are not relevant for younger cohorts, valuable information to tailor treatment to the needs of the older population can be gained. According to the sample size collection, which was based on the minimal important clinical difference of the Patient-Rated Wrist Evaluation, 92 patients will have to be included, with at least 46 patients in each treatment group. Enrollment began in July 2023 and is expected to continue until summer 2024. The final follow-up will be 2 years after the last patient is included. Although many trials on this topic have previously been published, there remains an ongoing debate regarding the optimal treatment for distal radius fractures in older patients. This observational study, which will use a fairly new methodological study design, will provide further information on treatment outcomes for older patients with distal radius fractures for which to date equipoise exists regarding the optimal treatment. DERR1-10.2196/52917.

Endovascular Repair of One-hundred Urgent and Emergent free or Contained Thoraco-abdominal Aortic Aneurysms Ruptures. An International Multi-Center Trans-Atlantic experience.

To analyze the outcomes of urgent/emergent endovascular aortic repair of patients with free/contained ruptured thoracoabdominal aortic aneurysms (rTAAA). Endovascular repair of rTAAA has been scarcely described in emergent setting. An international multicenter retrospective observational study (ClinicalTrials.govID:NCT05956873) from January-2015 to January-2023 in 6 European and 1 United States Vascular Surgery Centers. Primary end-points were technical success, 30-day and/or in-hospital mortality and follow-up survival. A total of 100 rTAAA patients were included (75 male; mean age 73y). All patients (86 contained and 14 free ruptures) were symptomatic and treated within 24-hours from diagnosis: multi-branched off-the-shelf devices (Zenith t-branch,Cook Medical Inc.Bjaeverskov,Denmark) in 88 patients, physician-modified endografts in 8, patient-specific device or parallel grafts in two patients each. Primary technical success was achieved in 89 patients and 30-day and/or in-hospital mortality was 24%. Major adverse events (MAEs) occurred in 34% of patients (permanent dialysis and paraplegia in 4 and 8 patients, respectively). No statistical differences were detected in mortality rates between free and contained ruptured patients (43%vs.21%; P =0.075). Multivariate analysis revealed contained rupture favoring technical success (Odd-Ratio10.1;95%Confidence-Interval:3.0-33.6; P =<0.001). MAEs (OR9.4;95%C-I:2.8-30.5; P =<0.001) and pulmonary complications (OR11.3;95%CI:3.0-41.5; P =<0.001) were independent risk factors for 30-day and/or in-hospital mortality. Median follow-up time was 13 months (interquartile range 5-24); 1-year survival rate was 65%. Aneurysm diameter>80mm (Hazard-Ratio:2.0;95%CI:1.0-30.5; P =0.037), technical failure (HR:2.6;95%CI:1.1-6.5; P =0.045) and pulmonary complications (HR:3.0;95%CI:1.2-7.9; P =0.021) were independent risk factors for follow-up mortality. Endovascular repair of rTAAA shows high technical success; the presence of free rupture alone appear not to correlate with early mortality. Effective prevention/management of post-operative complications is crucial for survival.

The Advent of Semi-Elective Lung Transplantation-Prolonged Static Cold Storage at 10°C.

Since the early days of clinical lung transplantation the preservation of donor organs has become a fairly standardized procedure and most centers do follow similar processes. This includes the use of low-potassium high dextran flush solutions and static cold storage (SCS) in a cooler filled with ice. Depending on the length of SCS, organs usually arrive at the recipient hospital at a temperature of 0°C-4°C. The question of the optimal storage temperature for donor lung preservation has been revisited as data from large animal experiments demonstrated that organs stored at 10°C experience less mitochondrial damage. Thus, prolonged cold ischemic times can be better tolerated at 10°C-even in pre-damaged organs. The clinical applicability of these findings was demonstrated in an international multi-center observational study including three high-volume lung transplant centers. Total clinical preservation times of up to 24hrs have been successfully achieved in organs stored at 10°C without hampering primary organ function and short-term outcomes. Currently, a randomized-controlled trial (RCT) is recruiting patients with the aim to compare standard SCS on ice with prolonged SCS protocol at 10°C. If, as anticipated, this RCT confirms data from previous studies, lung transplantation could indeed become a semi-elective procedure.

Antihypertensive efficacy and safety of azilsartan medoxomil in patients with diabetes mellitus in real clinical practice. According to the CONSTANT study

Background. Obesity and associated diseases are the most common comorbidities in patients with arterial hypertension (AH). The combination of AH and type 2 diabetes mellitus (DM2) significantly exacerbates the cardiovascular risk in this patients. BP control is one of the key components of the multivariate approach to reducing the risk of DM 2 complications. The use of drugs with pronounced antihypertensive properties and at the same time the ability to improve metabolic parameters should be a priority in this category of patients. Assessing the efficacy and safety of azilsartan medoxomil, the last molecule from the ARB class in patients with AH and DM 2 is an urgent task.Purpose. Evaluation of antihypertensive efficacy and safety of azilsartan medoxomil in patients with AH and DM 2 and overweight or obesity.Materials and methods. 235 overweight or obese patients with AH and DM2 enrolled in the international multicenter observational non-interventional prospective study CONSTANT with azilsartan medoxomil according to the approved label. The observation period is 6 months.Results. The dynamics of SBP by visit 4 (6 months) was 29,7±14,5 mmHg, DBP - 13,36±10,9 mmHg (r≤0,001). Overall, the group achieved BP targets in 211 (89.41%) DM patients enrolled in the study. Response to therapy (reduction in SBP by at least 20 mmHg, DBP of 10 mm Hg) was obtained in 177 (75.0%) patients. Glycated hemoglobin (p&lt;0.001) and fasting glucose (p&lt;0.001) significantly decreased in patients with AH and DM. A decrease in total cholesterol, triglycerides, and LDL was observed, including in DM patients not taking statins (p&lt;0.001). Overall, a decrease in waist circumference was observed across the group (p&lt;0.005).Conclusion. Azilsartan medoxomil in real clinical practice proved to be a highly effective antihypertensive drug in patients with AH and DM. The ability of the drug, including in combination with other drugs, to improve the metabolic profile, reduce the volume of adipose tissue makes it a priority drug of choice in patients with AH, obesity and type 2 DM.

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

BackgroundEarly mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave.MethodsThis is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs.ResultsMobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates.ConclusionsOur findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility.Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021).

Antihypertensive efficacy and safety of azilsartan medoxomil in patients with CАD, obesity and metabolic disorders. According to the CONSTANT study

Background: epidemiological studies show that the most common arterial hypertension (AH) is complicated by coronary artery disease (CAD), such patients are classified as very high risk. Effective BP control in this category of patients is critical. Therefore, assessing the efficacy and safety of current antihypertensive drugs in patients with AH and CAD against obesity or overweight is an important task.Purpose. Evaluation of antihypertensive efficacy and safety of azilsartan medoxomil in patients with overweight or obesity and stable CAD.Materials and methods. 335 patients with stable CAD and overweight or obese enrolled in the international multicenter observational non-interventional prospective study CONSTANT with azilsartan medoxomil according to the approved label. The observation period is 6 months.Results. The dynamics of SBP by visit 4 (6 months) was 30,1±15,3 mmHg, DBP – 12,5±10,4 mmHg (r≤0,001). Overall, 84,5% of patients enrolled in the study achieved BP targets across the group. Response to therapy (reduction in SBP by at least 20 mm Hg, DBP of 10 mm Hg) was obtained in 75,2% of patients. In patients who did not take statins, the level of cholesterol, triglycerides and LDL decreased significantly (p&lt;0,001), the HDL did not change significantly. In patients with diabetes mellitus, a decrease in glycated hemoglobin was recorded (p&lt;0,001). Overall, a decrease in waist circumference was observed across the group (p&lt;0,005).Conclusion. Azilsartan medoxomil has high antihypertensive properties, the ability to influence the metabolic profile and volume of adipose tissue, as well as tolerability comparable to placebo, which makes it the drug of choice in patients with AH with CAD and obesity or overweight in real clinical practice.

Result of the Physiologic Pacing Registry, an international multicenter prospective observational study of conduction system pacing

Conduction system pacing (CSP), including both left bundle branch area pacing (LBBAP) and His-bundle pacing (HBP) has been proposed as an alternative therapy option for patients with indication for cardiac pacing to treat bradycardia or heart failure. The purpose of this study was to evaluate implant success, safety, and electrical performances of HBP and LBBAP in the multinational Physiological Pacing Registry. The international prospective observational registry included 44 sites from 16 countries globally between November 2018 and May2021. Of 870 subjects enrolled, CSP lead implantation was attempted in 849 patients. Subjects with successful CSP lead implantation were followed for 6 months (5 ± 2 months). CSP lead implantation was successful in 768 patients (90.4%). Implant success was 95.2% (239/251) for LBBAP and 88.5% (529/598) for HBP (P = .002). Procedural duration and fluoroscopy duration were comparable between LBBAP and HBP (P = .537). Capture threshold at implant was 0.69 ± 0.39 V at 0.46 ± 0.15 ms in LBBAP and 1.44 ± 1.03 V at 0.71 ± 0.33 ms in HBP (P <.001). Capture threshold at 6 months was 0.79 ± 0.33 V at 0.44 ± 0.13 ms in LBBAP and 1.59 ± 0.97 V at 0.67 ± 0.31 ms in HBP (P <.001). Pacing threshold rise ≥1 V was observed at 6 months in 3 of 208 (1.4%) of LBBAP and 55 of 418 (13.2%) of HBP (P <.001). Serious adverse events related to implant procedure or CSP lead occurred in 5 of 251 (2.0%) with LBBAP and 25 of 598 (4.2%) with HBP (P = .115). This large prospective multicenter study demonstrates that CSP is technically feasible in most patients with relatively higher implant success and suggests that, with current technology, LBBAP may have better pacing parameters than HBP.

Prognostic significance of nodular number in patients undergoing hepatic resection of intermediate-stage hepatocellular carcinoma (BCLC Stage B): An international multicenter observational study

Prognostic significance of nodular number in patients undergoing hepatic resection of intermediate-stage hepatocellular carcinoma (BCLC Stage B): An international multicenter observational study

Ventilator-associated pneumonia in neurocritically ill patients: insights from the ENIO international prospective observational study

BackgroundAcute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality.MethodsPre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included.ResultsOut of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p < 0.001) were used. Independent risk factors for VAP occurrence were male gender, the use of IP, hypothermia, and the occurrence of tracheobronchitis during ICU stay. VAP was not an independent risk factor for ICU mortality (Hazard Ratio, HR = 0.71 95%CI 0.43–1.16, p = 0.168), but was independently associated with longer ICU stay (OR = 2.55 95%CI 2.01–3.23, p < 0.001).ConclusionsVAP is common in ABI patients. Male gender, IP and EVD insertion, tracheobronchitis, and the use of therapeutic hypothermia were significantly associated with VAP occurrence. VAP did not affect mortality but increased ICU-LOS.

AMplitude spectral area of ventricular fibrillation and amiOdarone Study in patients with out-of-hospital cArdIaC arrest. The MOSAIC study.

Antiarrhythmic drugs are recommended for out of hospital cardiac arrest (OHCA) with shock-refractory ventricular fibrillation (VF). Amplitude Spectral Area (AMSA) of VF is a quantitative waveform measure that describes the amplitude-weighted mean frequency of VF, it correlates with intramyocardial adenosine triphosphate (ATP) concentration, it is a predictor of shock efficacy and an emerging indicator to guide defibrillation and resuscitation efforts. How AMSA might be influenced by amiodarone administration is unknown. In this international multicentre observational study, all OHCAs receiving at least one shock were included. AMSA values were calculated by retrospectively analysing the pre-shock ECG interval of 2 s. Multivariable models were run and a propensity score based on the probability of receiving amiodarone was created to compare two randomly matched samples. 2,077 shocks were included: 1,407 in the amiodarone group and 670 in the non-amiodarone group. AMSA values were lower in the amiodarone group [8.8 (6-12.7) mV·Hz vs. 9.8 (6-14) mV·Hz, p = 0.035]. In two randomly matched propensity score-based groups of 261 shocks, AMSA was lower in the amiodarone group [8.2 (5.8-13.5) mV·Hz vs. 9.6 (5.6-11.6), p = 0.042]. AMSA was a predictor of shock success in both groups but the predictive power was lower in the amiodarone group [Area Under the Curve (AUC) non-amiodarone group 0.812, 95%CI: 0.78-0.841 vs. AUC amiodarone group 0.706, 95%CI: 0.68-0.73; p < 0.001]. Amiodarone administration was independently associated with the probability of recording lower values of AMSA. In patients who have received amiodarone during cardiac arrest the predictive value of AMSA for shock success is significantly lower, but still statistically significant.

Oxygen Consumption with High-Flow Nasal Oxygen versus Mechanical Ventilation- An International Multicenter Observational Study in COVID-19 Patients (PROXY-COVID).

The COVID-19 pandemic led to local oxygen shortages worldwide. To gain a better understanding of oxygen consumption with different respiratory supportive therapies, we conducted an international multicenter observational study to determine the precise amount of oxygen consumption with high-flow nasal oxygen (HFNO) and with mechanical ventilation. A retrospective observational study was conducted in three intensive care units (ICUs) in the Netherlands and Spain. Patients were classified as HFNO patients or ventilated patients, according to the mode of oxygen supplementation with which a patient started. The primary endpoint was actual oxygen consumption; secondary endpoints were hourly and total oxygen consumption during the first two full calendar days. Of 275 patients, 147 started with HFNO and 128 with mechanical ventilation. Actual oxygen use was 4.9-fold higher in patients who started with HFNO than in patients who started with ventilation (median 14.2 [8.4-18.4] versus 2.9 [1.8-4.1] L/minute; mean difference = 11.3 [95% CI 11.0-11.6] L/minute; P < 0.01). Hourly and total oxygen consumption were 4.8-fold (P < 0.01) and 4.8-fold (P < 0.01) higher. Actual oxygen consumption, hourly oxygen consumption, and total oxygen consumption are substantially higher in patients that start with HFNO compared with patients that start with mechanical ventilation. This information may help hospitals and ICUs predicting oxygen needs during high-demand periods and could guide decisions regarding the source of distribution of medical oxygen.

Current practices in nutrition therapy in cardiac surgery patients: An international multicenter observational study.

Cardiac surgery patients with a prolonged stay in the intensive care unit (ICU) are at high risk for acquired malnutrition. Medical nutrition therapy practices for cardiac surgery patients are unknown. The objective of this study is to describe the current nutrition practices in critically ill cardiac surgery patients worldwide. We conducted a prospective observational study in 13 international ICUs involving mechanically ventilated cardiac surgery patients with an ICU stay of at least 72 h. Collected data included the energy and protein prescription, type of and time to the initiation of nutrition, and actual quantity of energy and protein delivered (maximum: 12 days). Among 237 enrolled patients, enteral nutrition (EN) was started, on average, 45 h after ICU admission (range, 0-277 h; site average, 53 [range, 10-79 h]). EN was prescribed for 187 (79%) patients and combined EN and parenteral nutrition in 33 (14%). Overall, patients received 44.2% (0.0%-117.2%) of the prescribed energy and 39.7% (0.0%-122.8%) of the prescribed protein. At a site level, the average nutrition adequacy was 47.5% (30.5%-78.6%) for energy and 43.6% (21.7%-76.6%) for protein received from all nutrition sources. Critically ill cardiac surgery patients with prolonged ICU stay experience significant delays in starting EN and receive low levels of energy and protein. There exists tremendous variability in site performance, whereas achieving optimal nutrition performance is doable.

The effect of guideline-based antimicrobial therapy on the outcome of fracture-related infections (EAT FRI Study)

AimThis study investigated the compliance with a guideline-based antibiotic regimen on the outcome of patients surgically treated for a fracture-related infection (FRI). MethodIn this international multicenter observational study, patients were included when diagnosed with an FRI between 2015 and 2019. FRI was defined according to the FRI consensus definition. All patients were followed for at least one year. The chosen antibiotic regimens were compared to the published guidelines from the FRI Consensus Group and correlated to outcome. Treatment success was defined as the eradication of infection with limb preservation. ResultsA total of 433 patients (mean age 49.7 ± 16.1 years) with FRIs of mostly the tibia (50.6%) and femur (21.7%) were included. Full compliance of the antibiotic regime to the published guidelines was observed in 107 (24.7%) cases. Non-compliance was mostly due to deviations from the recommended dosing, followed by the administration of an alternative antibiotic than the one recommended or an incorrect use or non-use of rifampin. Non-compliance was not associated with a worse outcome: treatment failure was 12.1% in compliant versus 13.2% in non-compliant cases (p = 0.87). ConclusionsWe report good outcomes in the treatment of FRI and demonstrated that minor deviations from the FRI guideline are not associated with poorer outcomes.

Performance of D-Dimers in Patients with Prior History of Venous Thromboembolism Based on Anticoagulation Status

Background: D-dimers frequently stay elevated in patients with prior history of venous thromboembolism (VTE). Moreover, D-dimers seem to have lower diagnostic yield in patients presenting with a suspicion of recurrent VTE and it is not clear how D-dimers perform in patients on anticoagulation. Aim: To evaluate the performance of D-dimers in patients with a history of VTE based on anticoagulation status. Methods: The PREDICTORS study is an international prospective multicenter observational cohort study of outpatients with suspected VTE recurrence. The aim is to improve the performance of diagnostic strategies in patients with a suspicion of recurrent VTE. Pre-test clinical probability was assessed, and D-dimers were performed based on local clinical practices. Negative D-dimers were determined based on the manufacturer's threshold for every commercial assay used in each center. Recurrent VTE events (defined as proximal deep venous thrombosis or segmental or more proximal pulmonary embolism) at enrollment and during the 3-month follow-up were assessed and all suspected recurrent events were independently adjudicated. Results: D-dimer measurements were used in the diagnostic management of 482 patients, of which, 168 patients were on anticoagulation and 314 were not on anticoagulation. At enrollment, the prevalence of recurrent VTE was 29.9% (144/482). Moreover, at the index suspicion, 35.1% (169/482) had negative D-dimers. Amongst patients on anticoagulation, 4/90 (4.4%; 95%CI 1.2%-11.0%) and 21/78 (26.9%) had recurrent VTE at enrollment in patients with negative and positive D-dimers, respectively. During follow-up, no recurrent VTE occurred in patients with negative D-dimers. Amongst patients without anticoagulation, 2/79 (2.5%; 95%CI 0.3%-8.9%) and 117/235 (49.8%) had recurrent VTE at enrollment in patients with negative and positive D-dimers, respectively. One recurrent VTE occurred during follow-up amongst patients with initial negative D-dimers (1.3%; 95%CI 0.0-7.0%). Conclusion: In patients presenting with a suspected recurrent VTE, the prevalence of VTE was high, including in patients receiving anticoagulant therapy. Prevalence of VTE based on D-dimers positivity was comparable between patients on anticoagulation and patients without anticoagulation. False negative rate of D-dimers appears to be higher in patients with a suspicion of recurrent VTE than in patients with a suspected first thromboembolic event. Further studies are needed to assess if a change in the D-dimers cut-off could improve diagnostic yield.

Association of fecal and serum microRNA profiles with gastrointestinal cancer and chronic inflammatory enteropathy in dogs.

Reliable biomarkers to differentiate gastrointestinal cancer (GIC) from chronic inflammatory enteropathy (CIE) in dogs are needed. Fecal and serum microRNAs (miRNAs) have been proposed as diagnostic and prognostic markers of GI disease in humans and dogs. Dogs with GIC have fecal and serum miRNA profiles that differ from those of dogs with CIE. (a) identify miRNAs that differentiate GIC from CIE, (b) use high-throughput reverse transcription quantitative real-time PCR (RT-qPCR) to establish fecal and serum miRNA panels to distinguish GIC from CIE in dogs. Twenty-four dogs with GIC, 10 dogs with CIE, and 10 healthy dogs, all client-owned. An international multicenter observational prospective case-control study. Small RNA sequencing was used to identify fecal and serum miRNAs, and RT-qPCR was used to establish fecal and serum miRNA panels with the potential to distinguish GIC from CIE. The best diagnostic performance for distinguishing GIC from CIE was fecal miR-451 (AUC: 0.955, sensitivity: 86.4%, specificity: 100%), miR-223 (AUC: 0.918, sensitivity: 90.9%, specificity: 80%), and miR-27a (AUC: 0.868, sensitivity: 81.8%, specificity: 90%) and serum miR-20b (AUC: 0.905, sensitivity: 90.5%, specificity: 90%), miR-148a-3p (AUC: 0.924, sensitivity: 85.7%, specificity: 90%), and miR-652 (AUC: 0.943, sensitivity: 90.5%, specificity: 90%). Slightly improved diagnostic performance was achieved when combining fecal miR-451 and miR-223 (AUC: 0.973, sensitivity: 95.5%, specificity: 90%). When used as part of a diagnostic RT-qPCR panel, the abovementioned miRNAs have the potential to function as noninvasive biomarkers for the differentiation of GIC and CIE in dogs.

Benefit and toxicity of programmed death-1 blockade vary by ethnicity in patients with advanced melanoma: an international multicentre observational study.

Programmed cell death receptor-1 (PD-1) monotherapy is a standard treatment for advanced cutaneous melanoma, but its efficacy and toxicity are defined in white populations and remain poorly characterized in other ethnic groups, such as East Asian, Hispanic and African. To determine the efficacy and toxicity of PD-1 monotherapy in different ethnic groups. Clinical data for patients with unresectable or advanced melanoma treated with anti-PD-1 monotherapy between 2009 and 2019 were collected retrospectively from five independent institutions in the USA, Australia and China. Tumour response, survival and immune-related adverse events (irAEs) were compared by ethnicity (white vs. East Asian/Hispanic/African) across different melanoma subtypes: nonacral cutaneous (NAC)/unknown primary (UP) and acral/mucosal/uveal. In total, 1135 patients were included. White patients had significantly higher objective response rate (ORR) [54%, 95% confidence interval (CI) 50-57% vs. 20%, 95% CI 13-28%; adjusted P < 0·001] and longer progression-free survival (14·2 months, 95% CI 10·7-20·3 vs. 5·4 months, 95% CI 4·5-7·0; adjusted P < 0·001) than East Asian, Hispanic and African patients in the NAC and UP subtypes. White ethnicity remained independently associated with a higher ORR (odds ratio 4·10, 95% CI 2·48-6·81; adjusted P < 0·001) and longer PFS (hazard ratio 0·58, 95% CI 0·46-0·74; adjusted P < 0·001) in multivariate analyses after adjustment for age, sex, primary anatomical location, metastasis stage, baseline lactate dehydrogenase level, mutational status and prior systemic treatment. White and East Asian/Hispanic/African patients shared similar ORR and progression-free survival in acral/mucosal/uveal melanomas. Similar melanoma-subtype-specific ethnic discrepancies were observed in complete response rate and overall survival. White patients had higher rates of gastrointestinal irAEs but lower rates of endocrine, liver and other rare types of irAEs. These differences in irAEs by ethnicity were not attributable to varying melanoma subtypes. Ethnic discrepancy in clinical benefit is specific to melanoma subtype, and East Asian, Hispanic and African patients with NAC and UP melanomas have poorer clinical benefits than previously recognized. The ethnic discrepancy in toxicity observed across different melanoma subtypes warrants an ethnicity-based irAE surveillance strategy. More research is needed to elucidate the molecular and immunological determinants of these differences. What is already known about this topic? There is a great difference in response to immunotherapy between different subtypes of melanoma (cutaneous, mucosal, acral and uveal) in patients with advanced disease. What does this study add? Our data show for the first time that there are differences between different ethnic groups in terms of both response and toxicity to immunotherapy beyond the well-appreciated discrepancies due to melanoma subtype.