Prospective Multicenter Study Research Articles

[Analysis of compliance with lung protective mechanical ventilation strategy in patients with acute respiratory distress syndrome].

Objective: To assess the compliance with a lung protective ventilation strategy and to evaluate the relationship with prognosis in patients with acute respiratory distress syndrome (ARDS). Methods: In the prospective multicenter cohort study (CHARDS), patients with ARDS undergoing invasive mechanical ventilation were enrolled to collect essential information, mechanical ventilation data, and prognostic data. Compliance was operationally defined as tidal volume ≤7 ml/kg predicted body weight (PBW) or plateau pressure ≤30 cmH2O or driving pressure≤15 cmH2O. Tidal volume data collected 7 days prior to ventilation after ARDS diagnosis were categorized into four groups: standard group (Group A, 100% compliance), non-standard group (Group B, 50%-99% compliance, Group C,1%-49% compliance,and Group D,totally non-compliant). Plateau pressure and drive pressure measurements were recorded on the first day. Stepwise regression, specifically Logistics regression, was used to identify the factors influencing ICU survival. Results: A total of 449 ARDS patients with invasive mechanical ventilation were included; the proportion of mild, moderate, and severe patients was 71 (15.8%), 198 (44.1%) and 180 (40.1%), respectively. During the first 7 days, a total of 2880 tidal volume measurements were recorded with an average tidal volume of (6.89±1.93) ml/kg PBW. Of these measurements, 53.2% were found to be≤7 ml/kg PBW. The rates of compliance with lung protective mechanical ventilation were 29.8% (134/449), 24.5% (110/449), 23.6% (106/449), and 22% (99/449) in groups A, B, C, and D, respectively. In the standard group, the tidal volume for mild ARDS patients was 18.3%(13/71), while it was 81.7%(58/71)in the non-standard group. Similarly, in patients with moderate ARDS, the tidal volume was 25.8% (51/198) in the standard group, while it was 74.2% (147/198) in the non-standard group. Finally, in patients with severe ARDS, the tidal volume was 38.9% (70/180) in the standard group, while it was 61.1% (110/180) in the non-standard group. Notably, the compliance rate was higher in patients with moderate and severe ARDS in group A compared to patients with mild and moderate ARDS (18.3% vs. 25.8% vs. 38.9%, χ2=13.124, P=0.001). Plateau pressure was recorded in 221 patients, 95.9% (212/221) patients with plateau pressure≤30 cmH2O, and driving pressure was recorded in 207 patients, 77.8% (161/207) patients with a driving pressure ≤15 cmH2O.During the first 7 days, the mortality rate in the intensive care unit (ICU) was lower in the tidal volume standard group compared to the non-standard group (34.6% vs. 51.3%, χ2=10.464, P=0.001). In addition, the in-hospital mortality rate was lower in the standard group compared to the non-standard group (39.8% vs. 57%, χ2=11.016, P=0.001).The results of the subgroup analysis showed that the mortality rates of moderate and severe ARDS patients in the standard group were significantly lower than those in the non-standard group, both in the ICU and in the hospital (all P<0.05). However, there was no statistically significant difference in mortality among mild ARDS patients (all P>0.05). Conclusions: There was high compliance with recommended lung protective mechanical ventilation strategies in ARDS patients, with slightly lower compliance in patients with mild ARDS, and high compliance rates for plateau and drive pressures. The tidal volume full compliance group had a lower mortality than the non-compliance group, and showed a similar trend in the moderate-to-severe ARDS subgroup, but there was no significant correlation between compliance and prognosis in patients with mild ARDS subgroup.

Real-World Patent Foramen Ovale (PFO) Closure in Japan - 30-Day Clinical Outcomes From the AmplatzerTM PFO Occluder Japan Post-Marketing Surveillance Study.

The AmplatzerTM PFO Occluder was approved for marketing in Japan in May 2019, and the Amplatzer PFO Occluder Japan Post-marketing Surveillance (PFO Japan PMS) study was initiated in December 2019. This analysis presents 30-day clinical outcomes for PFO Japan PMS study patients.Methods and Results: PFO Japan PMS is a prospective single-arm non-randomized multicenter clinical study. Eligible patients were indicated for patent foramen ovale (PFO) closure and underwent an implant attempt with the AmplatzerTM PFO Occluder. Technical success was defined as successful delivery and release of the occluder; procedural success was defined as technical success with no serious adverse events (SAEs) within 1 day of the procedure. The primary safety endpoint includes predefined device- and/or procedure-related SAEs through 30 days after the procedure. From December 2019 to July 2021, 500 patients were enrolled across 53 Japanese sites. The mean (±SD) patient age was 52.7±15.4 years, and 29.8% of patients were aged >60 years. Technical and procedural success rates were both high (99.8% and 98.8%, respectively). Further, there was only one primary safety endpoint event (0.2%): an episode of asymptomatic paroxysmal atrial fibrillation that occurred 26 days after the procedure. In this real-world Japanese study with almost one-third of patients aged >60 years, PFO closure with the AmplatzerTM PFO Occluder was performed successfully and safely, with a low incidence of procedure-related atrial arrhythmias.

Perioperative Health Interventions in Children With Chronic Neuromuscular Conditions Undergoing Major Musculoskeletal Surgery: A Scoping Review.

Children with chronic neuromuscular conditions (CCNMC) have many coexisting conditions and often require musculoskeletal surgery for progressive neuromuscular scoliosis or hip dysplasia. Adequate perioperative optimization may decrease adverse perioperative outcomes. The purpose of this scoping review was to allow us to assess associations of perioperative health interventions (POHI) with perioperative outcomes in CCNMC. Eligible articles included those published from January 1, 2000 through March 1, 2022 in which the authors evaluated the impact of POHI on perioperative outcomes in CCNMC undergoing major musculoskeletal surgery. Multiple databases, including PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature, Web of Science, the Cochrane Library, Google Scholar, and ClinicalTrials.gov, were searched by using controlled vocabulary terms and relevant natural language keywords. Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines were used to perform the review. A risk of bias assessment for included studies was performed by using the Risk of Bias in Non-randomized Studies of Interventions tool. A total of 7013 unique articles were initially identified, of which 6286 (89.6%) were excluded after abstract review. The remaining 727 articles' full texts were then reviewed for eligibility, resulting in the exclusion of 709 (97.5%) articles. Ultimately, 18 articles were retained for final analysis. The authors of these studies reported various impacts of POHI on perioperative outcomes, including postoperative complications, hospital length of stay, and hospitalization costs. Because of the heterogeneity of interventions and outcome measures, meta-analyses with pooled data were not feasible. The findings reveal various impacts of POHI in CCNMC undergoing major musculoskeletal surgery. Multicenter prospective studies are needed to better address the overall impact of specific interventions on perioperative outcomes in CCNMC.

Cross-site validation of lung cancer diagnosis by electronic nose with deep learning: a multicenter prospective study

BackgroundAlthough electronic nose (eNose) has been intensively investigated for diagnosing lung cancer, cross-site validation remains a major obstacle to be overcome and no studies have yet been performed.MethodsPatients with lung cancer, as well as healthy control and diseased control groups, were prospectively recruited from two referral centers between 2019 and 2022. Deep learning models for detecting lung cancer with eNose breathprint were developed using training cohort from one site and then tested on cohort from the other site. Semi-Supervised Domain-Generalized (Semi-DG) Augmentation (SDA) and Noise-Shift Augmentation (NSA) methods with or without fine-tuning was applied to improve performance.ResultsIn this study, 231 participants were enrolled, comprising a training/validation cohort of 168 individuals (90 with lung cancer, 16 healthy controls, and 62 diseased controls) and a test cohort of 63 individuals (28 with lung cancer, 10 healthy controls, and 25 diseased controls). The model has satisfactory results in the validation cohort from the same hospital while directly applying the trained model to the test cohort yielded suboptimal results (AUC, 0.61, 95% CI: 0.47─0.76). The performance improved after applying data augmentation methods in the training cohort (SDA, AUC: 0.89 [0.81─0.97]; NSA, AUC:0.90 [0.89─1.00]). Additionally, after applying fine-tuning methods, the performance further improved (SDA plus fine-tuning, AUC:0.95 [0.89─1.00]; NSA plus fine-tuning, AUC:0.95 [0.90─1.00]).ConclusionOur study revealed that deep learning models developed for eNose breathprint can achieve cross-site validation with data augmentation and fine-tuning. Accordingly, eNose breathprints emerge as a convenient, non-invasive, and potentially generalizable solution for lung cancer detection.Clinical trial registrationThis study is not a clinical trial and was therefore not registered.

Evaluation of serological assays for the diagnosis of childhood tuberculosis disease: a study protocol

BackgroundTuberculosis (TB) poses a major public health challenge, particularly in children. A substantial proportion of children with TB disease remain undetected and unconfirmed. Therefore, there is an urgent need for a highly sensitive point-of-care test. This study aims to assess the performance of serological assays based on various antigen targets and antibody properties in distinguishing children (0–18 years) with TB disease (1) from healthy TB-exposed children, (2) children with non-TB lower respiratory tract infections, and (3) from children with TB infection.MethodsThe study will use biobanked plasma samples collected from three prospective multicentric diagnostic observational studies: the Childhood TB in Switzerland (CITRUS) study, the Pediatric TB Research Network in Spain (pTBred), and the Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infections in children and adolescents (ProPAED) study. Included are children diagnosed with TB disease or infection, healthy TB-exposed children, and sick children with non-TB lower respiratory tract infection. Serological multiplex assays will be performed to identify M. tuberculosis antigen-specific antibody features, including isotypes, subclasses, Fc receptor (FcR) binding, and IgG glycosylation.DiscussionThe findings from this study will help to design serological assays for diagnosing TB disease in children. Importantly, those assays could easily be developed as low-cost point-of-care tests, thereby offering a potential solution for resource-constrained settings.ClinicalTrials.gov IdentifierNCT03044509.

Artificial intelligence-based, semi-automated segmentation for the extraction of ultrasound-derived radiomics features in breast cancer: a prospective multicenter study

Abstract Purpose To investigate the feasibility of an artificial intelligence (AI)-based semi-automated segmentation for the extraction of ultrasound (US)-derived radiomics features in the characterization of focal breast lesions (FBLs). Material and methods Two expert radiologists classified according to US BI-RADS criteria 352 FBLs detected in 352 patients (237 at Center A and 115 at Center B). An AI-based semi-automated segmentation was used to build a machine learning (ML) model on the basis of B-mode US of 237 images (center A) and then validated on an external cohort of B-mode US images of 115 patients (Center B). Results A total of 202 of 352 (57.4%) FBLs were benign, and 150 of 352 (42.6%) were malignant. The AI-based semi-automated segmentation achieved a success rate of 95.7% for one reviewer and 96% for the other, without significant difference (p = 0.839). A total of 15 (4.3%) and 14 (4%) of 352 semi-automated segmentations were not accepted due to posterior acoustic shadowing at B-Mode US and 13 and 10 of them corresponded to malignant lesions, respectively. In the validation cohort, the characterization made by the expert radiologist yielded values of sensitivity, specificity, PPV and NPV of 0.933, 0.9, 0.857, 0.955, respectively. The ML model obtained values of sensitivity, specificity, PPV and NPV of 0.544, 0.6, 0.416, 0.628, respectively. The combined assessment of radiologists and ML model yielded values of sensitivity, specificity, PPV and NPV of 0.756, 0.928, 0.872, 0.855, respectively. Conclusion AI-based semi-automated segmentation is feasible, allowing an instantaneous and reproducible extraction of US-derived radiomics features of FBLs. The combination of radiomics and US BI-RADS classification led to a potential decrease of unnecessary biopsy but at the expense of a not negligible increase of potentially missed cancers.

A Comparison Study of Lymph Node Tuberculosis and Sarcoidosis Involvement to Facilitate Differential Diagnosis and to Establish a Predictive Score for Tuberculosis

Among 441 patients screened, 192 patients were included in the final analysis. The multivariate analysis showed that weight loss, necrotic granuloma, normal serum lysozyme level and hypergammaglobulinemia were significantly associated with TB. A risk score of TB was built based on these variables and was able to discriminate TB versus sarcoidosis with an AUC of 0.85 (95%CI: 0.79–0.91). Using the Youden’s J statistic, its most discriminant value (−0.36) was associated with a sensitivity of 80% and a specificity of 75%. Conclusion: We developed a score based on weight loss, necrotic granuloma, normal serum lysozyme level and hypergammaglobulinemia with an excellent capacity to discriminate TB versus sarcoidosis. This score needs still to be validated in a multicentric prospective study.

Echocardiographic evaluation of ventricular performance in VA-ECMO weaning: results from a observational multicentric prospective study

Abstract Funding Acknowledgements None. Background Although temporary mechanical circulatory support devices are increasingly used in the management of cardiogenic shock (CS), several open question regarding the kind of support and timing of institution/weaning remains open. Echocardiography is widely applied to drive the weaning process from VA-ECMO although there are no standardized protocols. Purpose We sought to evaluate the accuracy of echocardiographic indices in predicting successful weaning from VA-ECMO in CS patients. We tested total isovolumic time (tIVT), an index of ventricular performance(1,2), and longitudinal function (MAPSE) on top of the commonly used parameters (left ventricular ejection fraction, LVEF; E/e’ at mitral valve; left ventricular velocity time integral, LV VTI; TAPSE; right ventricular S’ at tissue Doppler imaging, RV S’). Methods Multicentric prospective study on adults receiving VA-ECMO due to refractory CS and/or cardiac arrest (CA) from 2012 to 2020. Echocardiography was performed at VA-ECMO placement and during the weaning trials. Waning trials were performed daily starting from 48 hours after VA-ECMO institution. A stepwise decrease of VA-ECMO blood flow was applied, until reaching 1 or 1.5 L/min. Successful weaning was defined as removal of VA-ECMO with no requirement for further MCS in the following 30 days. Results 76 patients were enrolled (23.8% female, 54.2±10.6 years-old), 52.6% due to CA. Median duration of VA-ECMO was 58 hours; 47 (61.8%) had intra-aortic balloon pump (IABP) inserted upfront. In-hospital mortality was 62.4% overall, 40% for CS without CA. 6 of the 32 weaned patients died in hospital for multiorgan failure due to septic shock. The baseline echocardiographic parameters associated with successful weaning were (Figure 1-A): stroke volume (SV) &amp;gt;13.2 ml (HR 4.12 [1.71-9.95], p 0.002), tIVT &amp;gt;23.6 min/sec (HR 0.14 [0.02-1.03], p 0.053), LV VTI &amp;gt;6.6 cm (HR 4.99 [1.94-12.87], p&amp;lt;0.001), MAPSE &amp;gt;6.15 mm (HR 4.42 [1.90-10.24], p 0.001), TAPSE &amp;gt;11 mm (HR 10.13 [1.37-7.02], p 0.023), RV S’ &amp;gt;7 cm (HR 5.40 [1.45-20.12], p 0.012). LVEF, E/e’ and S’ at mitral valve did not reach the statistical significance. Figure 1-B shows Kaplan-Meier analysis on echocardiographic indices collected during the last weaning trial; figure 2 details HR of all these parameters. Conclusions Echocardiography is pivotal in defining cardiac recovery and monitoring the weaning trial. Indices reflecting ventricular performance and delivered flow from LV were associated with weaning success both at VA-ECMO institution and throughout the weaning trials. Parameters reflecting ventricular activation and systo-diastolic interaction already demonstrated superiority in defining ventricular performance. Considering the known limitations of LVEF (HR, loading and LV dyssynchrony dependence), tIVT and MAPSE should be introduced in the standard evaluation in the acute setting.

Impact of perioperative high-protein nutritional support on postoperative outcomes in the treatment of primary lung cancer: Russian prospective multicenter comparative study (NUTRILUNC-study)

BACKGROUND: Up to 60% of lung cancer pts experience weight loss. Prevalence of sarcopenia in patients (pts) with non-small cell lung cancer (NSCLC) is about 43% and is an independent predictor of worse overall survival. It was shown that nutritional support improves outcomes in pts with cancer. AIM: To evaluate impact of perioperative nutritional support on surgical treatment outcomes of patients with NSCLC. MATERIALS AND METHODS: Patients with primary NSCLC (n=112, 69 males), aged 57,2±8,2, awaiting lung surgery and being at risk of malnutrition (Nutritional Risk Screening Assessment 2002 score ≥3) were randomized into 2 groups. Study group (n=55) received oral nutritional support (Nutridrink Compact Protein, Nutricia LLC), 250 ml/d (36 g of protein, 612 kcal) for 14 d before and 14 d after surgery in addition to standard diet. Control group (n=57) had a standard diet. The number of respiratory complications after surgery, length of hospitalization, anthropometric, functional, laboratory parameters, quality of life (according to Quality of Life Questionnaire Core-30) were assessed. Results were presented as mean ± standard deviation. Differences were considered significant at p ≤0.05. RESULTS: In the study group there were fewer respiratory complications (p 0.01), and a shorter length of hospitalization (p=0.03). Body weight in the study group did not change significantly, while in the control group it decreased (0.15±3.7 kg versus loss of 3.47±3.6 kg). Results of six-minute walk test and hand grip dynamometry were higher in the study group then in the control group (411.8±56.0 m versus 383.2±52.1 m; 33.5±8.4 kg versus 27.1±6.8 kg). Quality of life was better in the study group, p 0.05. The total protein and albumin levels were higher in the study group (70.9±5.6 g/l versus 63.1±4.0 g/l; 38.5±5.8 g/l versus 33.2±3.0 g/l). One patient in study group experienced 1st grade diarrhea. CONCLUSION: In patients with NSCLC at risk of malnutrition perioperative nutritional support with high protein oral nutritional support has a positive effect on surgical treatment outcomes.

Reclassification of CADILLAC risk score with lung ultrasound at admission in patients with STEMI in a one-year follow-up

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): JC-M received Original Research Projects Grant from the Catalan Society of Cardiology and LR-S received Scholarship for Training and Research from the Association of Ischemic Heart Disease and Cardiological Critical Care of the Spanish Society of Cardiology. Introduction Lung ultrasound (LUS) has emerged as a valuable diagnostic and prognostic tool in heart failure (HF) and shows promise in risk stratification for ST-segment elevation myocardial infarction (STEMI) during the acute phase. Current risk stratification scales for STEMI primarily rely on the Killip scale to assess the severity of heart failure (HF) upon admission. However, these scales were developed before the widespread use of LUS, and as a result, LUS findings have not been incorporated into any existing risk stratification scales for STEMI. Purpose To assess the potential improvement in prognostic predictive value achieved by incorporating LUS findings into a current risk score for STEMI. Methods In a prospective multicenter cohort study, an independent operator conducted LUS, and offline B-line counting was performed upon admission. Patients were categorized as having wet lung (at least one site with ≥3 B-lines) or dry lung based on LUS results. The CADILLAC score was calculated, and patients were classified as either low risk (≤2 points) or medium/high risk (&amp;gt;2 points). We evaluated the Net Reclassification Index (NRI) and conducted a Receiver Operating Characteristics (ROC) comparison based on the prediction of a composite endpoint which included death, hospitalization for HF, acute coronary syndrome, or stroke within one year following revascularization. Results The CADILLAC score was computed for 353 patients after excluding those admitted with Killip IV. Among these, 216 (61.2%) had a low-risk score (≤2), and 137 (38.8%) had a medium-high score. LUS significantly reclassified CADILLAC results, resulting in an absolute NRI of 12.4%. ROC comparison of models comprising CADILLAC and CADILLAC + LUS demonstrated that the addition of LUS significantly improved the accuracy of predicted risk (0.722 vs. 0.770, p=0.05). Conclusion The inclusion of LUS findings in the CADILLAC score enhances its prognostic capacity.Figure 1

Erratum: Prevalence of mental disorders, psychosocial distress, and perceived need for psychosocial support in cancer patients and their relatives stratified by biopsychosocial factors: rationale, study design, and methods of a prospective multi-center observational cohort study (LUPE study)

Erratum: Prevalence of mental disorders, psychosocial distress, and perceived need for psychosocial support in cancer patients and their relatives stratified by biopsychosocial factors: rationale, study design, and methods of a prospective multi-center observational cohort study (LUPE study)

Prognostic evaluation of ST-segment elevation acute myocardial infarction according to lung ultrasound in the acute phase

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): JC-M received an Original Research Projects Grant from the Catalan Society of Cardiology and LR-S received Scholarship for Training and Research from the Association of Ischemic Heart Disease and Cardiological Critical Care of the Spanish Society of Cardiology. Introduction Lung ultrasound (LUS) has emerged as a useful diagnostic and prognostic tool in heart failure (HF) and has shown promise in risk stratification for ST-segment elevation myocardial infarction (STEMI) in the acute phase. These studies consistently indicate that the degree of pulmonary congestion, assessed by the number of B-lines on LUS, is significantly associated with a worse prgnosis during hospitalization and short-term follow-up in STEMI patients. However, this prognostic value has mainly been evaluated during hospital admission or a few days after discharge without a long-term follow-up. Purpose To assess the prognostic value of LUS at one year in patients admitted for STEMI. Methods In a prospective multicenter cohort study involving STEMI patients, an independent operator performed LUS during the first 24 hours after revascularization and offline B-line counting was conducted. LUS results were assessed both as a categorical [wet (at least one site with ³3 B-lines)/dry lung] and continuous variable (total number of B-lines). The primary endpoint was a composite of death or hospitalization for HF, acute coronary syndrome, or stroke within one year. Results A total of 173 patients were included. The composite endpoint occurred in 13.7% of the patients over a median follow-up of 368 days. LUS was able to predict the composite outcome with hazard ratios (HR) of adjusted hazard ratios of 4.85 (95% CI 2.79-8.43) for having a wet lung and 1.13 (95% CI 1.09-1.18) for each B-line. After and adjustment for sex, age, chronic kidney disease, previous atrial fibrillation, Killip class and left ventricular ejection fraction HR was 1.72 (95% CI 0.91-3.28) for having a wet lung and 1.06 (95% CI 1.00-1.11) for each B-line. Conclusion Detecting B-lines on LUS predicts adverse events at one year in STEMI patients.Kaplan-Meier curves

Patterns of opioid use after surgical discharge: a multicentre, prospective cohort study in 25 countries.

Excessive opioid prescribing following surgery contributes to the growing opioid crisis. Prescribing practices are modifiable, yet data to guide appropriate prescription of opioids at surgical discharge remain sparse. This study aimed to evaluate factors associated with opioid consumption following discharge from surgery. An international prospective multicentre cohort study was performed recruiting adult patients undergoing common general, orthopaedic, gynaecological and urological surgery, with follow-up 7 days after discharge. The primary outcome measures were the quantities of prescribed and consumed opioids in oral morphine milligram equivalents. Descriptive and multivariable analyses were performed to investigate factors associated with the primary outcome measures. This analysis included 4273 patients from 144 hospitals in 25 countries. Overall, 1311 (30.7%) patients were prescribed opioids at discharge. For those patients prescribed opioids, mean (SD) 179 (240) oral morphine milligram equivalents were prescribed, yet only 81 (145) oral morphine milligram equivalents were consumed within the first 7 days after discharge. An increased dose of opioids prescribed at discharge was associated with an increased dose of opioids consumed during the follow-up period (β = 0.33 (95%CI 0.31-0.34), p < 0.001). The risk of prescribing more opioids than patients consumed increased as quantities of opioids prescribed at discharge exceeded 100 oral morphine milligram equivalents, independent of patient comorbidity, procedure and pain. Patients were prescribed more than twice the quantity of opioids they consumed in the first 7 days following discharge from surgery. Our data suggest that the current quantities of opioids provided at discharge exceed patient needs and may contribute to increasing community opioid use and circulation.

Cardiogenic shock in general intensive care unit: a nationwide prospective analysis of epidemiology and outcome

Abstract Funding Acknowledgements None. Background Cardiogenic shock (CS) is a heterogenous, life-threatening disease burdened by a mortality up to 50%. An increasing incidence of the CS related to other etiological causes, including acute decompensated heart failure, has been reported. However, most of the epidemiological data are derived from patients admitted to dedicated acute cardiac care units. Epidemiology and management of CS patients admitted to general intensive care unit (ICU) in Italy is yet unexplored. Purpose To describe the epidemiology, patients feature, management and outcome of CS patients admitted to Italian general ICUs. Methods Prospective multicentric epidemiological study. Over 600 thousand patients admitted to 316 hundred Italian general intensive care units from 2011 to 2018 were screened trough PROSAFE software. The Margherita PROSAFE project is an observational project for the continuous electronic collection of data on patients admitted to ICUs; it is developed by the GiViTI (Gruppo italiano per la valutazione degli interventi in terapia intensiva - Italian Group for the Evaluation of Interventions in Intensive Care Medicine). The primary outcome of the analysis was hospital mortality. Secondary outcomes included description of patients features and management. Results 11661 patients (72.1±12.1 years old.; 39.5% women) with a diagnosis of CS were included in the analysis. ICU and in-hospital mortality were respectively 45.5 % and 53.9%. Highest mortality was observed for pulmonary embolism (58.4%), right heart failure (56.3%) and acute decompensated heart failure (ADHF) (44.2%). 46.9% of patients presented with more than 3 organ failure (panel A). CS commonest aetiologies were ADHF (63,3%), acute myocardial infarction (19.8%) and right heart failure (11%). Invasive mechanical ventilation was used in the 88.6% of cases. Intra-aortic balloon pump was placed in 15.2%, with higher frequency in ischemic aetiologies (43.9%) and ADHF (13.7%); VA-ECMO was most frequently placed in the right heart failure (3.7%) and acute myocardial infarction (2.6%) groups. The factors independently associated with increased hospital mortality were increasing age (p &amp;lt;0.001), lower Glasgow coma scale (p &amp;lt;0.001), hypoxemia (PaO2 &amp;lt;100, OR: 1.91; 95% Cl: 1.58 – 2.3; p &amp;lt;0.001), bradycardia (OR: 1.84; 95% Cl: 1.49 – 2.26; p &amp;lt;0.001), hypotension (OR: 1.27; 95% Cl: 1.12 – 1.43; p &amp;lt;0.001), bilirubin above 12 mg/dl (OR: 7.90; 95% Cl: 2.56 – 24.3), increased creatinine (p &amp;lt;0.001) and reduced platelets (&amp;lt;50000 U/mL, OR: 2.43; 95% Cl: 1.78 – 3.31; p &amp;lt;0.001) (panel B). Curiously, in the predictive model a BMI above normal values was protective as well as tachycardia compared to severe bradycardia (panel C). Conclusions The etiology of CS in general intensive care units is heterogeneous with acute heart failure being the commonest. The mortality rate remains unacceptably high with right heart failure and acute heart failure being burden by the worst outcome.

Clinical effectiveness of drop-in mental health services at paediatric hospitals: A non-randomised multi-site study for children and young people and their families - study protocol.

Despite the high prevalence of mental health difficulties in children and young people with long-term health conditions (LTCs), these difficulties and experiences are often overlooked and untreated. Previous research demonstrated the effectiveness of psychological support provided via a drop-in mental health centre located in a paediatric hospital. The aim of this prospective non-randomised single-arm multi-centre interventional study is to determine the clinical effectiveness of drop-in mental health services when implemented at paediatric hospitals in England. It is hypothesised that families who receive psychological interventions through the drop-in services will show improved emotional and behavioural symptoms. Outcomes will be measured at baseline and at 6-month follow-up. The primary outcome is the difference in the total difficulties score on the Strengths and Difficulties Questionnaire (SDQ) reported by parent or child at 6 months. Secondary outcomes include self and parent reported Paediatric Quality of Life Inventory (PedsQL), self-reported depression (PHQ-9) and anxiety measures (GAD-7) and family satisfaction (CSQ-8). This trial aims to determine the clinical effectiveness of providing psychological support in the context of LTCs through drop-in mental health services at paediatric hospitals in England. These findings will contribute to policies and practice addressing mental health needs in children and young people with other long-term health conditions. ISRCTN15063954, Registered on 9 December 2022.

Machine learning with electrocardiograms to optimize mortality risk stratification in patients with suspected acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute (NHLBI) and National Center for Advancing Translational Sciences (NCATS). Background The importance of risk stratification in patients with suspected acute coronary syndrome (ACS) extends beyond diagnosis and immediate treatment. It influences the precision of care delivery and the allocation of resources to those at highest risk of adverse events. Purpose We sought to evaluate the prognostic value of electrocardiogram (ECG) feature-based machine learning models to risk-stratify long-term mortality in those with suspected ACS. Methods This was a multicenter prospective observational cohort study of consecutive, non-traumatic patients evaluated at the emergency department for suspected ACS. The derivation cohort included 4,015 patients from a University Medical Center (age 59±16 years, 47% women, 80% training with 10-fold cross-validation and 20% testing). Ascertainment of all-cause death was based on numerous data sources, including the Centers for Disease Control and Prevention’s National Death Index registry. We trained six machine learning methods for survival analysis using 73 morphological ECG features from presenting prehospital 10-second 12-lead ECGs. We used predicted risk scores in a variational Bayesian Gaussian mixture model to define three risk groups corresponding to low, moderate, and high-risk and compared the resulting classification performance against the HEART score. The external testing cohort included 3,095 patients from a University (age 59±15 years, 44% women). Results The mortality rate was 20.3% in the derivation cohort after an average follow-up period of 3.53 years (IQR 1.75 - 5.32). Extra Survival Trees outperformed other forecasting models during cross-validation. In the internal testing cohort, the derived risk groups were significantly predictive of survival (Kaplan-Meier log-rank test statistic = 121.14, p&amp;lt;0.001), outperforming the classification performance using the HEART score (Figure 1). Our machine learning-based risk stratification model detected &amp;gt;90% of death events missed by low-risk HEART score (Figure 2). Ruling-out the low-risk group, it achieved a negative predictive value of 93.4% with a sensitivity of 85.9% (compared to 89.0% and 75.0%, respectively, for the HEART score). This classification performance generalized well to our external testing cohort. Compared to those in the low-risk group, patients at moderate (OR = 3.62 [1.35-9.74]) and high (OR = 6.12 [2.38-15.75]) risk had significantly higher odds of 30-day cardiovascular death (n=109, 3.5%). Conclusions Using only features from the 10-second 12-lead ECG, we derived and externally validated a machine learning model that stratifies the mortality risk of patients during long-term follow up. This model outperformed current standard of care based on the HEART score. Future work should validate the potential of this decision-support tool in influencing treatment plans and resource allocation.Figure 1.Clustering performanceFigure 2.Sankey diagram

Characteristics, management and prognosis of patients with coronary artery disease undergoing coronary intervention and atrial fibrillation

Abstract Funding Acknowledgements None. Introduction The selection of antithrombotic treatment in patients with ischaemic heart disease (IHD) and atrial fibrillation (AF) represents a challenge when trying to balance ischaemic and haemorrhagic risk. However, there is little "real-life" data on the selected antithrombotic treatment and its short and long-term prognosis. Methods A Prospective multicentre study that includes patients with IHD [acute coronary syndrome (ACS) or chronic coronary syndrome (CCS)] and AF admitted to 13 Spanish centres. The objective is to describe the characteristics, antithrombotic treatment and prognosis of patients undergoing PCI and AF. Results 373 patients were included. The average age was 77.6 ± 9.8 years (28% women). Patients had a high ischaemic and haemorrhagic risk [CHA2DS2VASc 4 (2-5) and HASBLED 3 (2-4)], with 25.5% being frail according to the Clinical Frailty Scale. The main reason for admission was ACS (44.8% NSTEMI, 22.2% STEMI and 33% CCS ), and 49.8% of patients had multivessel disease. 70.3% of patients underwent revascularisation, mainly percutaneously (92.2%). Among those percutaneously revascularised, the most used antithrombotic treatment was triple therapy with double antiplatelet therapy (DAPT) + oral anticoagulant (OAC) (62.5%), followed by double therapy with monoantiplatelet therapy + OAC (29.2%). In revascularised patients over 80, the most selected antithrombotic therapy was similar: 60.5% and 28.9%, respectively. The most used OAC was apixaban (42.3%), followed by vitamin K antagonists (17.3%). One-year survival was 88.5%. 2.6% of patients presented an ischemic stroke, and 4.8% suffered a new ACS. At the same time, haemorrhagic events (BARC ≥2) were 8.9%. Conclusions A high ischaemic and haemorrhagic risk co-exists in patients with IHD and AF. In our setting, triple therapy, mainly with the use of DOACs over VKA, is the preferred therapy. The long-term mortality of this subgroup of patients with IHD is high (&amp;gt;10%), with a rate of haemorrhagic events (8.9%) higher than ischaemic events (4.8%).Characteristics of patients

Comparing Sonazoid contrast-enhanced ultrasound to contrast-enhanced CT and MRI for differentially diagnosing renal lesions: a prospective multicenter study.

To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.

Activated clotting time-guided heparinization during open AAA surgery: a pilot study

BackgroundArterial thrombo-embolic complications (TEC) are still common during and after non-cardiac arterial procedures (NCAP). While unfractionated heparin has been used during NCAP for more than 70 years to prevent TEC, there is no consensus regarding the optimal dosing strategy. The aim of this pilot study was to test the effectiveness and feasibility of an activated clotting time (ACT)-guided heparinization protocol during open abdominal aortic aneurysm (AAA) surgery, in anticipation of a randomized controlled trial (RCT) investigating if ACT-guided heparinization leads to better clinical outcomes compared to a single bolus of 5000 IU of heparin.MethodsA prospective multicentre pilot study was performed. All patients undergoing elective open repair for an AAA (distal of the superior mesenteric artery) between March 2017 and January 2020 were included. Two heparin dosage protocols were compared: ACT-guided heparinization with an initial dose of 100 IU/kg versus a bolus of 5000 IU. The primary outcome was the effectiveness and feasibility of an ACT-guided heparinization protocol with an initial heparin dose of 100 IU/kg during open AAA surgery. Bleeding complications, TEC, and mortality were investigated for safety purposes.ResultsA total of 50 patients were included in the current study. Eighteen patients received a single dose of 5000 IU of heparin and 32 patients received 100 IU/kg of heparin with additional doses based on the ACT. All patients who received the 100 IU/kg dosing protocol reached the target ACT of > 200 s. In the 5000 IU group, TEC occurred in three patients (17%), versus three patients (9.4%) in the 100 IU/kg group. Bleeding complications were found in six patients (33%) in the 5000 IU group and in 9 patients (28%) in the 100 IU/kg group. No mortality occurred in either group.ConclusionsThis pilot study demonstrated that ACT-guided heparinization with an initial dose of 100 IU/kg appears to be feasible and leads to adequate anticoagulation levels. Further randomized studies seem feasible and warranted to determine whether ACT-guided heparinization results in better outcomes after open AAA repair.

Multimorbidity-associated emergency hospital admissions: a “screen and link” strategy to improve outcomes for high-risk patients in sub-Saharan Africa: a prospective multicentre cohort study protocol

Background The prevalence of multimorbidity (the presence of two or more chronic health conditions) is rapidly increasing in sub–Saharan Africa. Hospital care pathways that focus on single presenting complaints do not address this pressing problem. This has the potential to precipitate frequent hospital readmissions, increase health system and out-of-pocket expenses, and may lead to premature disability and death. We aim to present a description of inpatient multimorbidity in a multicentre prospective cohort study in Malawi and Tanzania. Primary objectives Determine prevalence of multimorbid disease among adult medical admissions and measure patient outcomes. Health Economic: Measure economic costs incurred and changes in health-related quality of life (HRQoL) at 90 days post-admission. Situation analysis: Qualitatively describe pathways of patients with multimorbidity through the health system. Secondary objectives Determine hospital readmission free survival and markers of disease control 90 days after admission. Health Economic: Present economic costs from patient and health system perspective, sub-analyse costs and HRQoL according to presence of different diseases. Situation analysis: Understand health literacy related to their own diseases and experience of care for patients with multimorbidity and their caregivers. Methods This is a prospective longitudinal cohort study of adult (≥18 years) acute medical hospital admissions with nested health economic and situation analysis in four hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Malawi; 3) Hai District Hospital, Boma Ng’ombe, Tanzania; 4) Muhimbili National Hospital, Dar-es-Salaam, Tanzania. Follow-up duration will be 90 days from hospital admission. We will use consecutive recruitment within 24 hours of emergency presentation and stratified recruitment across four sites. We will use point-of-care tests to refine estimates of disease pathology. We will conduct qualitative interviews with patients, caregivers, healthcare providers and policymakers; focus group discussions with patients and caregivers, and observations of hospital care pathways.