Large Prospective Multicenter Study Research Articles

Coffee consumption and adverse cardiovascular events in patients with atrial fibrillation

BackgroundThere is some evidence of reduced major cardiovascular event (MACE) rates associated with moderate coffee consumption in the general population. However, there is concern about the potential risks of coffee consumption in patients with atrial fibrillation (AF). Therefore, we aimed to investigate the association between coffee consumption and MACE in AF patients.MethodsData of patients with documented AF enrolled in two large prospective observational multicenter cohort studies (Swiss-AF and Beat-AF) were analyzed. Follow-up information was obtained on a yearly basis. Coffee consumption was categorized into two main groups: “daily” and “not-daily” coffee consumers as well as additional subcategories. The primary endpoint was MACE, defined as a composite of stroke or systemic embolism, myocardial infarction, hospitalization for acute heart failure, and cardiovascular mortality. Secondary endpoints were the individual components of MACE and all-cause mortality. We performed time-updated multivariable adjusted Cox regression analyses to investigate the association between coffee consumption and MACE.ResultsThe incidence rate for MACE was 5.09 per 100 person-years (py) in daily and 7.49 per 100 py in not-daily consumers (median follow-up duration: 4.7 years). After adjustment for pre-selected confounding variables, daily coffee consumption was associated with a 23% lower hazard for MACE compared to not-daily consumption (hazard ratio (HR) (95% confidence interval (CI)) 0.77 (0.66; 0.89)). Patients with moderate coffee consumption (2–3 cups/day) had the lowest hazard for MACE compared to patients with not-daily coffee consumption (HR (95% CI) 0.74 (0.63; 0.87)).ConclusionsIn a population of AF patients, daily coffee consumption was associated with a reduced risk for MACE, hospitalization for acute heart failure, and all-cause mortality. The results were inconclusive for stroke or systemic embolism, myocardial infarction, and cardiovascular death. In this analysis, we found no evidence of an unfavourable association of daily coffee consumption in AF Patients with adverse outcome events.Trial registrationClinicalTrials.gov Identifier: NCT02105844.

Effect of high sensitivity C-reactive protein on uric acid-related cardiometabolic risk in patients with coronary artery disease—a large multicenter prospective study

Although serum uric acid (SUA) is a risk factor for cardiometabolic outcome, but it remains unclear which patients with coronary artery disease (CAD) benefit the most from SUA lowering therapy (ULT). The association of SUA level, systemic inflammation and cardiometabolic risk is still unclear. The current study is aimed to examine whether SUA-associated cardiometabolic risk is modulated by systemic inflammation in CAD patients. A total of 16,598 CAD patients with baseline high-sensitivity C-Reactive Protein (hsCRP) and SUA available were included. Baseline and follow-up data were collected. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infarction and stroke. In patients with hsCRP ≥ 2 mg/L, increasing quintiles of SUA were significantly associated with increased rates of 2-year MACCE (adjusted p < 0.001 for trend, p = 0.037 for interaction). Each unit increase in SUA levels was associated with a 11.3% increased risk of MACCE (adjusted p < 0.001, p = 0.002 for interaction). However, in patients with hsCRP < 2 mg/L, increasing quintiles of SUA were not associated with increased MACCE (adjusted p = 0.120). Elevated SUA levels are related to MACCE when hsCRP levels are 2 mg/L or more but not less than 2 mg/L. This finding suggests a potential benefit of combined ULT and anti-inflammation therapy in patients with hyperuricemia and greater systemic inflammation.

What Is Needed to Determine and Potentially Improve the Clinical Effectiveness and Cost-Effectiveness of Robot-Assisted Reconstructive Urinary Tract and Pelvic Floor Surgery?-ICI-RS 2024.

Robot-assisted (RA) surgery has many advantages for urinary tract and pelvic floor reconstruction (UTPFR) but its application is only slowly increasing. Studies are limited in number, patients and follow-up duration. The low-volume high-complexity nature of UTPFR warrants specific research to evaluate the potential role of the RA approach. During its 2024 meeting in Bristol, the International Consultation on Incontinence-Research Society (ICI-RS) reviewed the current literature on RA UTPFR. Priority research questions and strategies were explored in a proposal. Four different topics were discussed. (1) Large multicentre prospective studies on RA UTPFR are needed to evaluate clinical effectiveness and safety. The RA approach needs to be prioritized in specific procedures and patients, to first improve patient care where gains are highest. (2) Models for cost-utility analysis for RA UTPFR are needed to (re)direct limited resources as efficiently as possible in a quickly changing technological field. (3) A modular curriculum for training UTPFR surgeons to become RA certified needs to be developed, to allow valid interpretation and comparison of outcomes. (4) Technological improvements to address tissue handling, accessibility, efficiency and sustainability are needed. Digitalization can be a gamechanger for RA UTPFR through telesurgery (training and expertize coverage), augmented reality and artificial intelligence providing intra-operative assistance, assessment and feedback. The proposal discussed the need for studies on clinical and cost effectiveness, safety, and training curriculum development for RA UTPFR. Recent technological developments hold great promise for RA UTPFR. High-priority research questions were identified.

Association between cardiac consultation and outcomes in patients with perioperative myocardial infarction/injury

Abstract Introduction Perioperative cardiac complications are a frequent occurrence and can lead to high short- and long-term mortality rates after major noncardiac surgery. No single intervention has yet demonstrated its effectiveness in treating perioperative myocardial infarction/injury (PMI). In this large prospective multicentre study, we aimed to evaluate the association between postoperative cardiac consultation and major adverse cardiac event (MACE) and all-cause death within 365 days in patients with PMI after undergoing major noncardiac surgery. Methods We prospectively included consecutive patients undergoing major inpatient noncardiac surgery at two hospitals who were eligible for the institutional active PMI surveillance and response programme. For this analysis, only patients with PMI who were directly transferred to the regular ward following surgery were included. In the case of a PMI, the standardised structured institutional response included assessing the patient for possible symptoms, recording a 12-lead ECG and a cardiac consultation. The specific scope of the PMI workup and management was determined by the attending clinical cardiologist following an institutional flowchart. Our primary endpoint was the occurrence of MACE (defined as a composite of cardiovascular death, MI, AHF, and life-threatening arrhythmia) within 365 days, excluding the initial PMI. All-cause death after 365 days was the secondary endpoint. Multivariable Cox proportional hazard models were used to evaluate the association of cardiac consultation with MACE and all-cause death after 365 days. Results During the period between October 2014 and September 2019, the BASEL-PMI study programme enrolled 14294 patients. After the exclusion of patients without PMI, with a postoperative ICU stay, multiple inclusion, or palliative setting 1048 patients remained. Among those, 434 patients received postoperative cardiac consultation (41.4%). Patients had a median age of 77 years and 44.8% were female. After adjustment, patients who received a postoperative cardiac consultation had a lower risk of having MACE after 365 days (adjusted hazard ratio [aHR] = 0.54, 95% confidence interval [CI] 0.37 - 0.79, p-value = 0.001) and a lower risk of death of any cause after 365 days (aHR = 0.66, 95%CI 0.44 - 1.00, p-value = 0.048). Conclusion In a large multicentre prospective cohort study, postoperative cardiac consultation in patients with PMI was associated with a reduced risk of MACE and all-cause death after 365 days.Kaplan-Meier curve for MACE

Lipoprotein (a), coronary artery disease risk, and MACE in individuals without standard modifiable risk factors in the UK Biobank

Abstract Background A significant proportion of patients with coronary artery disease (CAD) lack standard modifiable risk factors (SMuRFs; smoking, hypercholesterolaemia, diabetes and hypertension), for example with recent analyses demonstrating that around 25% of patients with ST-elevation myocardial infarction are SMuRF-less(1). With continued focus on primary prevention in cardiovascular disease, the SMuRF-less subset is likely to increase over time. A body of evidence has implicated lipoprotein (a) in CAD, but no such studies have investigated this association in a purely SMuRF-less population. Purpose To investigate the role of lipoprotein (a) in predicting CAD risk and major adverse cardiovascular events (MACE) in a large, SMuRF-less cohort. Methods The UK Biobank is a large prospective multicentre study which recruited over 500,000 participants in the UK aged 37-73 years at entry between 2006-2010. SMuRFs were defined as 1) smoking (current or historical), 2) hypercholesterolaemia – lipid lowering medication on enrolment or total cholesterol &amp;gt;5.5mmol/L or LDL-C &amp;gt;3.5mmol/L, 3) previous diagnosis of diabetes mellitus, or HbA1c &amp;gt;48mmol/mol, 4) previous diagnosis of hypertension. MACE was defined as a composite of coronary artery disease – previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft surgery –, stroke, or all-cause mortality. Results Of the total UK Biobank cohort, 46,139 participants were identified as SMuRF-less together with a valid lipoprotein (a) level. Median follow-up duration was 12yrs. In univariate analyses (Table 1), there was no significant difference in lipoprotein (a) concentrations between individuals with and without MACE (16.9 vs. 17.1nmol/L respectively, p = 0.913). The overall event rate was low, with just 3% MACE (1381 events) overall. Older age, male gender, apolipoprotein A, apolipoprotein B, HbA1c level, HDL cholesterol level and body mass index were all associated with MACE. In regard to all-cause mortality alone, there was no association with lipoprotein (a) level, although the other aforementioned parameters were all significantly associated with this outcome. Similarly, lipoprotein (a) was not a significant predictor of stroke. However, there was a large difference in lipoprotein (a) levels between patients with and without CAD (27.2 vs. 17.1nmol/L respectively, p = 0.004). In Kaplan-Meier analysis, lipoprotein (a) level above the 77th percentile (60.3nmol/L) was significantly associated with CAD (p=0.032). In Cox regression models, despite the low event rate, lipoprotein (a) was a significant predictor of CAD (HR 1.00-1.01, p=0.01), and importantly the only potentially modifiable parameter (N = 39,433, 111 events, Table 2). Conclusion Lipoprotein (a) independently predicts CAD in those without SMuRFs, highlighting the importance of checking this parameter in such patients, particularly given the novel antisense technologies in development which may lower lipoprotein (a)(2).Univariate analysesCox regression for CAD

The impact of obesity on pediatric orthopedic polytrauma patients

Objectives: The effect of obesity on fracture care and management in the adult population has been well documented in the literature; there is a scarcity of evidence-based research reporting the impact of obesity on pediatric orthopedic polytrauma patients. The aim of this study was to objectively investigate the impact of obesity on pediatric orthopedic polytrauma patients to optimize care and fracture management. Methods: A single-center retrospective cohort study of pediatric polytrauma patients aged 2–18 years old admitted to a level 1 trauma center was conducted over three years. Patients were categorized based on their body mass index (BMI). A logistic regression model was used to identify significant variables between the study groups. Results: A total of 60 patients were included in the analysis and divided into normal weight group (n = 36) and overweight/obese group (n = 24). A trend of lower injury severity score (ISS) was observed in the overweight/obese group compared to the normal weight group. Non-orthopedic injuries, including head, chest, and abdominal injuries, were found to be less in the overweight/obese group. Higher rates of spine and extremity fractures were reported in the overweight/obese group, as well as the need for surgical fixation (P = 0.05). No specific differences in complications, outcome, or discharge facility were found between the two groups. Conclusion: The paradoxical association between BMI and ISS/non-orthopedic injuries, in contrast to spine and extremity fractures, reflects the complex relationship between obesity and polytrauma patterns. Large multi-center prospective studies are needed to predict clinical outcomes in pediatric orthopedic polytrauma patients.

Diagnosis Algorithm of Cardiac Sarcoidosis: Where Are We?

This commentary discusses the recently published article, "Speckle-tracking echocardiography as an effective screening tool for cardiac involvement among patients with systemic sarcoidosis in an Indian cohort: A prospective observational study". Owing to improved imaging modalities and increased awareness of cardiac sarcoidosis (CS), the prevalence of CS has risen. Given that CS is a relatively rare condition with high mortality, it is essential for the initial test to demonstrate high sensitivity. However, several guidelines offer differing opinions on the diagnosis algorithm for CS. This commentary highlighted the importance of speckle-tracking echocardiography as an effective screening tool. Due to its high negative predictive value (NPV), it would be useful to rule out cardiac involvement. Nevertheless, larger prospective multicenter studies are warranted to develop a more cost-effective diagnosis algorithm for CS.

The prognostic utility of Lactate/Albumin*Age score in septic patient with normal lactate level

BackgroundA previous study has shown that the lactate/albumin*age (LAA) score is useful for predicting mortality in patients with sepsis admitted to the ICU. We aimed to evaluate the clinical significance of the LAA score in patients with sepsis who presented to the emergency department (ED) MethodsThis retrospective observational study used data from the Korean Shock Society Registry collected between January 2017 and December 2021. The prognostic performance of the LAA score for predicting the 28-day mortality was evaluated. Lactate and albumin levels were measured immediately after arrival to the ED. ResultsOf the 5346 patients with sepsis, data from 3240 were analyzed. The area under the receiver operating characteristic curve (AUROC) of the LAA score (0.737, 95 % confidence interval (CI) 0.716–0.757), was higher than that of lactate (0.699, 95 % CI 0.677–0.720, p < 0.001), lactate/albumin (LA) ratio (0.730, 95 % CI 0.709–0.751, p = 0.016), and Sequential Organ Failure Assessment (SOFA) score (0.698, 95 % confidence interval 0.676–0.720, p = 0. 004), and Acute Physiology and Chronic Health Evaluation (APACHE) II scores (0.672; 95 % confidence interval 0.649–0.694, p < 0.001). The optimal cut-off value for the LAA score was 119.9. In the Kaplan-Meier analysis according to the optimal cutoff value, the 28-day mortality rates were higher in the high LAA score group (log-rank test, p < 0.001). The LAA score was independently associated with 28-day mortality in the multivariate Cox proportional hazards model (adjusted hazard ratio 2.07, 95 % CI 1.76–2.43, p < 0.001). In the normal (<2 mmol/L) lactate group, the AUROC value for LAA score was higher than LA ratio (normal group 0.674 vs 0.634, p < 0.004). In patients over 65 years old, LAA score (0.731) showed a higher AUROC value than LA ratio (0.725). (p < 0.001) ConclusionThe LAA score may be used as an independent predictor of mortality in patients with sepsis in the emergency department. Our results show that it performs better than serum lactate alone, LA ratio, and SOFA and APACHE II scores. While this suggests that the LAA could provide clinicians with a useful tool for timely early intervention and care planning in patients with a poor prognosis, further validation in large multicenter prospective studies are necessary to confirm its reliability and practicality as a readily available and objective biomarker.

Pre-transplant Loco-Regional Therapy for Hepatocellular Carcinoma and Post-transplant Outcomes: A National Study.

The ultimate preferred treatment for hepatocellular carcinoma (HCC) complicated with cirrhosis and portal hypertension is an orthotopic liver transplant (OLT). Loco regional therapy (LRT) has emerged to prevent tumor growth and progression of disease beyond the Milan criteria to achieve transplant. There is a paucity of data regarding safety, posttransplant survival benefits, and tumor recurrence rate achieved by these LRT modalities. We aim to assess and compare the five-year survival rate and tumor recurrence rate with or without LRT in patients after OLT with diagnosed HCC utilizing the nation's largest dataset. This is a retrospective observational study approved by Saint Louis University institutional review board. We utilized the largest dataset from the years 2003-2013 where pertaining data were gathered from Organ Procurement Transplant Network (OPTN) standard analysis and research files (STAR) through novel linkages with Medicare bills. Descriptive and comparative statistics were performed. 2412 (51.6%) patients received any form of locoregional therapy (single or combination) out of 4669 total study sample size. The overall five-year survival in the study sample was 76.1%. There was statistically no significant improvement seen in five-year posttransplant survival in the group that received one mode of LRT (adjusted hazard ratio (aHR) 0.97, P<0.64) or a combination of LRT (aHR 0.94, P<0.58) in comparison to those that received none after adjusting donor and recipient clinical characteristics. However, five-year survival trended higher among those treated with combination therapy over those treated with single LRT or none. Overall HCC recurrence was 4.8%, while no significant difference was noted when comparing above-mentioned groups. Five-year posttransplant survival and HCC recurrence rate were also found to have no difference when compared between above-mentioned groups after adjusting explant pathology. This is the largest retrospective study comparing liver transplant patients with HCC who received LRT to none. Although it did not show any statistically significant benefit of single or combination of LRT on survival or tumor recurrence after liver transplant for HCC patients, the outcomes encourage the safe and feasible use of LRT as a bridging therapy. Our study also suggests an observed pattern of improved posttransplant survival and tumor recurrence rate with combination loco-regional therapy. Larger multicenter prospective studies will be required to achieve the effect size to determine the best therapies for maximizing patient survival cost-effectively.

Changes in quality of life 1 year after intensive care: a multicenter prospective cohort of ICU survivors

BackgroundWith survival rates of critical illness increasing, quality of life measures are becoming an important outcome of ICU treatment. Therefore, to study the impact of critical illness on quality of life, we explored quality of life before and 1 year after ICU admission in different subgroups of ICU survivors.MethodsData from an ongoing prospective multicenter cohort study, the MONITOR-IC, were used. Patients admitted to the ICU in one of eleven participating hospitals between July 2016 and June 2021 were included. Outcome was defined as change in quality of life, measured using the EuroQol five-dimensional (EQ-5D-5L) questionnaire, and calculated by subtracting the EQ-5D-5L score 1 day before hospital admission from the EQ-5D-5L score 1 year post-ICU. Based on the minimal clinically important difference, a change in quality of life was defined as a change in EQ-5D-5L score of ≥ 0.08. Subgroups of patients were based on admission diagnosis.ResultsA total of 3913 (50.6%) included patients completed both baseline and follow-up questionnaires. 1 year post-ICU, patients admitted after a cerebrovascular accident, intracerebral hemorrhage, or (neuro)trauma, on average experienced a significant decrease in quality of life. Conversely, 11 other subgroups of ICU survivors reported improvements in quality of life. The largest average increase in quality of life was seen in patients admitted due to respiratory disease (mean 0.17, SD 0.38), whereas the largest average decrease was observed in trauma patients (mean -0.13, SD 0.28). However, in each of the studied 22 subgroups there were survivors who reported a significant increase in QoL and survivors who reported a significant decrease in QoL.Conclusions This large prospective multicenter cohort study demonstrated the diversity in long-term quality of life between, and even within, subgroups of ICU survivors. These findings emphasize the need for personalized information and post-ICU care.Trial registration: The MONITOR-IC study was registered at ClinicalTrials.gov: NCT03246334 on August 2nd 2017.

Updates in diagnosis and treatment of pediatric antiphospholipid syndrome.

This review offers an overview of the most important recent articles on pediatric APS. Non-thrombotic extra criteria manifestations were prevalent in pediatric APS. Pregnancy morbidity has been described as the first manifestation of APS at youth age, impairing gestational outcomes. The 2023 APS criteria were developed for adult APS patients, and there is still a lack of pediatric-specific APS criteria. Catastrophic APS was more commonly reported as the initial manifestation of pediatric APS than in adults. Regarding treatment, direct oral anticoagulants have been recently approval for pediatric patients with venous thrombosis. New approaches have been proposed for severe cases, for arterial thrombosis, and rituximab for refractory cases. Recurrences typically occurred early and were associated with older age at diagnosis. Current studies highlighted the multifaceted nature of pediatric APS. Further large prospective multicenter studies evaluating new medications capable of reducing recurrence risk and improving prognosis in this population will be required.

Probability assessment of pulmonary embolism using clinical and laboratory variables in hospitalized patients: A single-center, retrospective observational study

IntroductionPulmonary embolism (PE) probability assessment relies on clinical scoring systems, which have limitations for certain patient populations. We aimed to investigate the use of laboratory values for PE probability assessment. Materials and methodsThis retrospective single-center observational study included patients with suspected PE. Nineteen variables were examined. Logistic regression analysis adjusted for confounding factors was performed, and significant variables were used to develop a scoring method. Receiver operating characteristic (ROC) curves were used to detect PE and determine the optimal cutoff value. Well's scores were also estimated. ResultsThe model achieved an accuracy of 84.6 %. Hypocapnia, fever, alkaline phosphatase (ALP), D-dimer, and lactate levels had predictive values. The slope was negative for hypocapnia, ALP, and lactate, and positive for fever and D-dimer levels. Fever, with an adjusted odds ratio (OR) of 1.995, received a score of 2 for values above the cutoff, whereas the remaining variables were assigned a score of 1. Patients with PE had significantly higher scores (mean ± SD: 2.07 ± 0.91) than those without PE (1.80 ± 1.13; P = 0.001). The area under the ROC curve was 0.585 (95 % confidence interval: 0.563–0.606; P = 0.001). Using a cutoff score of 1.5 based on the maximum Youden's index, the scoring system achieved a sensitivity of 73.1 % and specificity of 43.4 %. The Well's score demonstrated a sensitivity of 51.1 % and specificity of 75.1 %. ConclusionThis study showed statistically significant laboratory values for the probability assessment of PE and the tentative scoring system (PAPEL score). Larger prospective multicenter studies are required to validate this scoring method in a wider population.

Safety and Tolerability of Continuous Inhaled Iloprost Therapy for Severe Pulmonary Hypertension in Neonates and Infants.

This is a single-center retrospective study to assess the safety and tolerability of continuous inhaled iloprost use as rescue therapy for refractory pulmonary hypertension (PH) in critically ill neonates and infants. A retrospective chart review was performed on 58 infants and data were collected at baseline, 1, 6, 12, 24, 48 and 72 h of iloprost initiation. Primary outcomes were change in heart rate (HR), fraction of inspired oxygen (FiO2), mean airway pressures (MAP), blood pressure (BP) and oxygenation index (OI). Secondary outcomes were need for extracorporeal membrane oxygenation (ECMO) and death. 51 patients treated for >6 h were analyzed in 2 age groups, neonate (≤28 days: n = 32) and infant (29-365 days: n = 19). FiO2 (p < 0.001) and OI (p = 0.01) decreased, while there were no significant changes in MAP, BP and HR. Of the fifteen patients placed on ECMO, seven were bridged off ECMO on iloprost and eight died. Twenty-four out of fifty-one patients (47%) recovered without requiring ECMO, while twelve (23%) died. Iloprost as add-on therapy for refractory PH in critically ill infants in the NICU has an acceptable tolerability and safety profile. Large prospective multicenter studies using iloprost in the neonatal ICU are necessary to validate these results.

Primary Embolization of Cerebral Arteriovenous Malformations With Intention to Cure: A Systematic Review of Literature and Meta-Analysis.

The treatment of brain arteriovenous malformations (AVMs) involves multiple approaches, including embolization, microsurgical resection, and radiosurgery. With the advent of new embolisates, dual-lumen balloon catheters, detachable tip microcatheters, and transvenous embolization, endovascular AVM obliteration has become more effective. Although adjuvant embolization and embolization are commonly used, the safety and effectiveness of curative embolization remain unclear. We conducted a systematic literature review using PubMed, Ovid Medline, and Web of Science to identify studies reporting outcomes in patients with AVMs who underwent primary embolization with the intention to cure. We collected data on patient characteristics, AVM features, complications, and radiographic and clinical outcomes for meta-analysis. We identified 25 studies with a total of 1425 patients with 1427 AVMs who underwent curative embolization. Of these patients, 70% were low grade (pooled = 61% [39-82]), 67% were <3 cm (pooled = 78% [60-92]), and 75% were in superficial locations (pooled = 80% [72-86]). At last radiographic follow-up (mean, 16.7 ± 10.9 months), the full obliteration rate was 52% (pooled = 61% [43-77]) and retreatment rate was 25% (pooled = 17% [8.3-27]). At last clinical follow-up (mean, 24.2 ± 13.3 months), the poor clinical outcome rate was 7.9% (pooled = 4.4% [1.3-8.7]) and symptomatic complication rate was 13% (pooled = 13% [8-19]). There was no significant difference in the rate of radiographic cure, need for retreatment, and poor outcomes between ruptured and unruptured AVMs. Symptomatic complications were more common in the treatment of unruptured AVMs. The primary outcomes showed high heterogeneity (I2 = 72%-94%). Curative embolization of AVM is primarily reserved for small and low-grade AVMs, with highly variable outcomes. Our findings suggest poor radiographic outcomes and increased risk of complications. Outcomes are highly dependent on patient selection and technique used. Large multicenter prospective studies are required to further guide patient selection, categorize clinical and radiographic outcomes, and identify subgroup of patients that may benefit from curative embolization.

Use of Immune Profiling Panel to assess the immune response of septic patients for prediction of worsening as a composite endpoint

Sepsis induces intense, dynamic and heterogeneous host response modulations. Despite improvement of patient management, the risk of mortality and healthcare-associated infections remains high. Treatments to counterbalance immune response are under evaluation, but effective biomarkers are still lacking to perform patient stratification. The design of the present study was defined to alleviate the limitations of existing literature: we selected patients who survived the initial hyperinflammatory response and are still hospitalized at day 5–7 after ICU admission. Using the Immune Profiling Panel (IPP), a fully automated RT-qPCR multiplex prototype, we optimized a machine learning model combining the IPP gene expression levels for the identification of patients at high risk of worsening, a composite endpoint defined as death or secondary infection, within one week after sampling. This was done on 332 sepsis patients selected from two retrospective studies. The IPP model identified a high-risk group comprising 30% of patients, with a significant increased proportion of worsening events at day 28 compared to the low-risk group (49% vs. 28%, respectively). These preliminary results underline the potential clinical application of IPP for sepsis patient stratification in a personalized medicine perspective, that will be confirmed in a larger prospective multicenter study.

Nerve transfer for upper extremity reanimation in people with spinal cord injury: A 2-year follow-up case series

Objective To describe the 2-year functional outcomes of nerve transfer (NT) for upper extremity reanimation. Study Design A prospective case series. Setting A highly specialized rehabilitation hospital for spinal cord injury (SCI) in Italy. Intervention Upper limb nerve transfer (32 NTs, 15 upper limbs). Participants Twelve male individuals with traumatic SCI (AIS A or B, neurological level from C4 to C7) were enrolled; 24-month follow-up data were available for 11. Outcome measures We evaluated the strength recovery of recipient muscles through the Medical Research Council (MRC) Scale for Muscle Strength. Upper limb function and independence were assessed with the Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) test version 1 and the Spinal Cord Independent Measure III (SCIM III). Patient satisfaction was also evaluated. Results After 24 months, median MRC scores (range) were: triceps 2 (1–2); extensor digitorum communis 3 (1–4); extensor pollicis longus 2.5 (1–4); flexor digitorum profundus 2 (0–4); flexor pollicis longus 2 (0–4). No complication occurred. GRASSP prehension ability and prehension performance total scores significantly improved at 24 months from 1 (0–4) to 2 (0–7) and from 1 (0–8) to 5 (0–-22), respectively. The SCIM III self-care sub-scale score improved at 24-month follow-up (p = 0.009). This study has important limitations, including a limited generalizability of the results and a small sample size that does not allow definitive conclusions to be drawn. A large multicenter prospective study is needed to confirm our findings. Conclusions NT represents a functional surgery option with few complications for the resuscitation of upper limbs in persons with tetraplegia.

Diagnosis of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: data from a practice-based longitudinal cohort

BackgroundA large prospective multicenter cohort study with systematic follow-up recently reported a 2.3% 2-year cumulative incidence of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE). ObjectivesThe present investigation aimed to determine the reported prevalence and incidence of CTEPH diagnosis after acute PE in real-world practice over a 12-year period. MethodsThis study was based on nationwide ambulatory billing claims and drug prescription data of all residents with public health insurance in Germany from 2010 to 2021. ResultsA total of 573 972 patients with acute PE (median age, 71 years; 57.4% women) were identified between 2010 and 2021. Prevalence of CTEPH among patients with history of PE increased during the period from 0.4% in 2010 to 0.9% in 2021. CTEPH was diagnosed in 2556 patients after acute PE, with most (17.6%) diagnoses reported within the first 3 months after the index PE event. The cumulative incidence rate after 3 months (first quarter) was calculated at 0.08% and after the first 2 years (eighth quarter) at 0.36%; it was 0.75% over the entire (90-month) follow-up period. Patients with CTEPH diagnosis during follow-up more often had right ventricular dysfunction at the index acute PE (14.9% vs 8.3%; P < .001). ConclusionThe low CTEPH incidence rate after acute PE in the present analysis suggests low awareness of CTEPH. It further suggests a lack of systematic follow-up protocols for acute PE survivors in the real world. Improved implementation of existing recommendations on follow-up strategies after PE is warranted.

Immunogenicity of COVID-19 booster vaccination in IEI patients and their one year clinical follow-up after start of the COVID-19 vaccination program.

Previous studies have demonstrated that the majority of patients with an inborn error of immunity (IEI) develop a spike (S)-specific IgG antibody and T-cell response after two doses of the mRNA-1273 COVID-19 vaccine, but little is known about the response to a booster vaccination. We studied the immune responses 8 weeks after booster vaccination with mRNA-based COVID-19 vaccines in 171 IEI patients. Moreover, we evaluated the clinical outcomes in these patients one year after the start of the Dutch COVID-19 vaccination campaign. This study was embedded in a large prospective multicenter study investigating the immunogenicity of COVID-19 mRNA-based vaccines in IEI (VACOPID study). Blood samples were taken from 244 participants 8 weeks after booster vaccination. These participants included 171 IEI patients (X-linked agammaglobulinemia (XLA;N=11), combined immunodeficiency (CID;N=4), common variable immunodeficiency (CVID;N=45), isolated or undefined antibody deficiencies (N=108) and phagocyte defects (N=3)) and 73 controls. SARS-CoV-2-specific IgG titers, neutralizing antibodies, and T-cell responses were evaluated. One year after the start of the COVID-19 vaccination program, 334 study participants (239 IEI patients and 95 controls) completed a questionnaire to supplement their clinical data focusing on SARS-CoV-2 infections. After booster vaccination, S-specific IgG titers increased in all COVID-19 naive IEI cohorts and controls, when compared to titers at 6 months after the priming regimen. The fold-increases did not differ between controls and IEI cohorts. SARS-CoV-2-specific T-cell responses also increased equally in all cohorts after booster vaccination compared to 6 months after the priming regimen. Most SARS-CoV-2 infections during the study period occurred in the period when the Omicron variant had become dominant. The clinical course of these infections was mild, although IEI patients experienced more frequent fever and dyspnea compared to controls and their symptoms persisted longer. Our study demonstrates that mRNA-based booster vaccination induces robust recall of memory B-cell and T-cell responses in most IEI patients. One-year clinical follow-up demonstrated that SARS-CoV-2 infections in IEI patients were mild. Given our results, we support booster campaigns with newer variant-specific COVID-19 booster vaccines to IEI patients with milder phenotypes.

Organ involvement in newly diagnosed sarcoidosis patients in the Netherlands: The first large European multicentre prospective study

BackgroundClinical presentation and prevalence of organ involvement is highly variable in sarcoidosis and depends on ethnic, genetic and geographical factors. These data are not extensively studied in a Dutch population. AimTo determine the prevalence of organ involvement and the indication for systemic immunosuppressive therapy in newly diagnosed sarcoidosis patients in the Netherlands. MethodsTwo large Dutch teaching hospitals participated in this prospective cohort study. All adult patients with newly diagnosed sarcoidosis were prospectively included and a standardized work-up was performed. Organ involvement was defined using the WASOG instrument. ResultsBetween 2015 and 2020, a total of 330 patients were included, 55% were male, mean age was 46 (SD 14) years. Most of them were white (76%). Pulmonary involvement including thoracic lymph node enlargement was present in 316 patients (96%). Pulmonary parenchymal disease was present in 156 patients (47%). Ten patients (3%) had radiological signs of pulmonary fibrosis. Cutaneous sarcoidosis was present in 74 patients (23%). Routine ophthalmological screening revealed uveitis in 29 patients (12%, n = 256)). Cardiac and neurosarcoidosis were diagnosed in respectively five (2%) and six patients (2%). Renal involvement was observed in 11 (3%) patients. Hypercalcaemia and hypercalciuria were observed in 29 (10%) and 48 (26%, n = 182) patients, respectively. Hepatic involvement was found in 6 patients (2%). In 30% of the patients, systemic immunosuppressive treatment was started at diagnosis. ConclusionsHigh–risk organ involvement in sarcoidosis is uncommon at diagnosis. Indication for systemic immunosuppressive therapy was present in a minority of patients.

Management of long bone fractures and traumatic hip dislocations in paediatric patients: study protocol for a prospective global multicentre observational cohort registry

IntroductionManagement controversy and clinical equipoise exist in treatments of long bone fractures and traumatic hip dislocation in paediatric patients due to the lack of high-quality clinical evidence. This protocol describes...