Global Cohort Research Articles

Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study.

We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population.

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking. A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan-Meier curves with log-rank tests were used to analyze time-to-event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival. Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI-specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis. GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.

TAVI for treating severe aortic valve disease in cardiogenic shock: a single centre experience

Abstract Introduction Recent evidence shows the safety and efficacy of TAVI in patients with aortic valve disease (AVD) presenting in cardiogenic shock (CS). However, there is limited data regarding CS management in the cardiac intensive care unit (CICU) and its outcomes. We aimed to describe the CS features, pre-TAVI management and short-term clinical outcomes of a cohort of CS patients (pts) submitted to TAVI. Methods Single-centre retrospective registry of consecutive pts with AVD undergoing TAVI in CS, from January 2020 to October 2023. CS was defined as pre-procedural hypotension/hypoperfusion requiring vasoactive drugs or mechanical circulatory support (MCS) devices. The severity of CS was defined according to the SCAI classification. Procedural related outcomes according to the VARC-3 criteria and 30-day mortality were assessed. Results A total of 16 pts (1% of our global TAVI cohort, 62% male, mean age 79±5 years) meet the inclusion criteria. The majority (n=13) presented severe aortic stenosis, two had degenerated aortic bioprosthesis with severe regurgitation and one had native valve severe regurgitation. 6 pts (38%) had isolated left ventricle (LV) dysfunction and 10 (62%) had biventricular dysfunction. The admission LVEF was 33±8% and the mean transaortic gradient for those with aortic stenosis was 46±13mmHg. The EuroSCORE II estimated for a single non-CABG emergency procedure was 37±15%. All patients were refused for surgical treatment upon Heart Team discussion. At admission, 12 (75%) patients presented in CS SCAI-C, 1 (6%) in SCAI-D and 3 (19%) in SCAI-E. These last 3 patients presented in cardiac arrest upon admission to the CICU (time to ROSC from 2 to 15 minutes). The peak lactate level at 48 hours was 3.4 mmol/L [2.1-5.1] and the highest Vasoactive-Inotropic Score (VIS) during admission was 21 [11-45]. None of the patients needed MCS pre-TAVI. 5 (31%) patients required invasive mechanical ventilation and 5 (31%) renal replacement therapy. Median time between CICU admission and transfemoral TAVI was 2.5 days [IQR 1-7]. Procedural success was 100%, with 57% receiving a balloon-expandable and 43% a self-expandable valve. Post-TAVI CICU length of stay was 6 days [IQR 5-9]. Most common procedural complication were the need for permanent pacemaker implantation (n=2, 12%) and access-related bleeding (n=2, 12%). Hospital length-of-stay was 20±15 days. Thirty-day mortality was 12% (n=2). Conclusion In this cohort of CS patients selected for TAVI treatment, procedural success was achieved in all cases. While complications were similar to the general TAVI population, in-hospital mortality remained high but very acceptable. These results suggest that, if correctly selected, aortic valve disease patients in CS represent a niche for whom brief stabilization and urgent percutaneous valve treatment might impact their dismal prognosis.

Inflammatory Neuropathy Consortium base (INCbase): a protocol of a global prospective observational cohort study for the development of a prediction model for treatment response in chronic inflammatory demyelinating polyneuropathy

BackgroundINCbase is an international, multicenter prospective observational study using a customizable web-based modular registry to study the clinical, biological and electrophysiological variation and boundaries of chronic inflammatory demyelinating polyneuropathy (CIDP). The primary objective of INCbase is to develop and validate a clinical prediction model for treatment response.MethodsAll patients meeting clinical criteria for CIDP can be included in INCbase. Collected data include demographics, clinical history, diagnostics and various domains of clinical outcomes. Data is collected at a minimum of every 6 months for two years, and more frequently at the discretion of the investigational site to allow for assessment of unexpected changes in treatment response or clinical status. Participants can be enrolled in various sub-studies designed to capture data relevant to specific groups of interest. Data is entered directly into the web-based data entry system by local investigators and/or participants. Collection and local storage of biomaterial is optional. To develop a clinical prediction model for treatment response, newly diagnosed patients with active disease warranting start of first-line treatment will be included. The study population will be split into a development and validation cohort. Univariate and multivariate logistic regression analysis will be used to identify and combine predictors at start of treatment for treatment response at six months. Model performance will be assessed through discrimination and calibration in an external validation cohort. The externally validated prediction model will be made available to researchers and clinicians on the INCbase website.DiscussionWith this study, we aim to create a clinically relevant and implementable prediction model for treatment response to first line treatments in CIDP. INCbase enrollment started in April 2021, with 29 centers across 8 countries and 303 patients participating to date. This collaborative effort between academia, patient advocacy organizations and pharmaceutical industry will deepen our understanding of how to diagnose and treat CIDP.

Incorporating replication in higher education: Supervisors’ perspectives and institutional pressures

ABSTRACT Background: Even though replication research has gained traction within academia over the recent years, it is not often well-received as a stand-alone thesis topic by supervisors and university administrators. Methods: In this qualitative investigation, we delve into the perspectives of academic supervisors on the feasibility of replication as a thesis topic within the field of applied linguistics (AL). Drawing on Institutional Theory, administrative pressures facing supervisors on what to be considered permissible for a thesis were also explored. By conducting semi-structured e-mail interviews with a global cohort of AL supervisors and a thematic analysis of their responses, a nuanced landscape was brought to light. Results: Supervisors outlined numerous benefits associated with replication including fostering academic advancement as well as providing opportunities for reevaluating prior research. Nonetheless, they also pointed to several obstacles along the way, such as concerns over originality, constraints on time and resources, and the necessity for mentorship. Moreover, supervisors emphasized their pivotal role as decision-makers in accepting or rejecting replication for a thesis project, while acknowledging the partial influence of institutional pressures. Conclusions: Lastly, some implications and recommendations on allocating more resources to replication research are provided.

Clinical characterization, prognostic, and predictive values of HER2-low in patients with early breast cancer in the PALLAS trial (ABCSG-42/AFT-05/BIG-14–13/PrE0109)

BackgroundBidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC).MethodsPALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression’s value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models.ResultsFrom the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p < 0.001) and was more frequent in patients enrolled in North America (63.1%) than in Europe (53.4%) or other regions (53.4%) (p < 0.001). HER2 status was not significantly associated with iDFS in a multivariable Cox model (hazard ratio 0.93, 95% confidence interval 0.81 – 1.06). No significant interaction was observed between treatment arm and HER2 status for iDFS (p = 0.43). Similar results were obtained for DRFS and OS.ConclusionsIn this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes.

New insights on genetic background of major diabetic vascular complications

BackgroundBy 2045, it is expected that 693 million individuals worldwide will have diabetes and with greater risk of morbidity, mortality, loss of vision, renal failure, and a decreased quality of life due to the devastating effects of macro- and microvascular complications. As such, clinical variables and glycemic control alone cannot predict the onset of vascular problems. An increasing body of research points to the importance of genetic predisposition in the onset of both diabetes and diabetic vascular complications.ObjectivesPurpose of this article is to review these approaches and narrow down genetic findings for Diabetic Mellitus and its consequences, highlighting the gaps in the literature necessary to further genomic discovery.Material and methodsIn the past, studies looking for genetic risk factors for diabetes complications relied on methods such as candidate gene studies, which were rife with false positives, and underpowered genome-wide association studies, which were constrained by small sample sizes.ResultsThe number of genetic findings for diabetes and diabetic complications has over doubled due to the discovery of novel genomics data, including bioinformatics and the aggregation of global cohort studies. Using genetic analysis to determine whether diabetes individuals are at the most risk for developing diabetic vascular complications (DVC) might lead to the development of more accurate early diagnostic biomarkers and the customization of care plans.ConclusionsA newer method that uses extensive evaluation of single nucleotide polymorphisms (SNP) in big datasets is Genome-Wide Association Studies (GWAS).

AcFibroMASH Index for the Diagnosis of Fibrotic MASH and Prediction of Liver-related Events: An International Multicenter Study

Background & AimsMetabolic dysfunction-associated steatohepatitis (MASH) and fibrotic MASH are significant health challenges. This multi-national study aimed to validate the acMASH index (including serum creatinine and aspartate aminotransferase concentrations) for MASH diagnosis and develop a new index (acFibroMASH) for non-invasively identifying fibrotic MASH and exploring its predictive value for liver-related events (LREs). MethodsWe analyzed data from 3,004 individuals with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) across 29 Chinese and nine international cohorts to validate the acMASH index and develop the acFibroMASH index. Additionally, we utilized the independent external data from a multi-national cohort of 9,034 patients with MAFLD to examine associations between the acFibroMASH index and the risk of LREs. ResultsIn the pooled global cohort, the acMASH index identified MASH with an AUROC of 0.802 (95%CI 0.786-0.818). The acFibroMASH index (including the acMASH index plus liver stiffness measurement) accurately identified fibrotic MASH with an AUROC of 0.808 in the derivation cohort and 0.800 in the validation cohort. Notably, the AUROC for the acFibroMASH index was 0.835 (95% CI 0.786-0.882), superior to that of the FAST score at 0.750 (95% CI 0.693-0.800, P<0.01) in predicting the 5-year risk of LREs. Patients with acFibroMASH >0.39 had a higher risk of LREs than those with acFibroMASH <0.15 (adjusted-hazard ratio: 11.23 95%CI 3.98-31.66). ConclusionsThis multi-ethnic study validates the acMASH index as a reliable, non-invasive test for identifying MASH. The newly proposed acFibroMASH index is a reliable test for identifying fibrotic MASH and predicting the risk of LREs.

Bibliometric Analysis of the Development of Entrepreneurial Ecosystem Research in Global Publications

This study conducts a comprehensive bibliometric analysis of the field of entrepreneurial ecosystems, mapping the evolving landscape of research from 1995 to 2024. Utilizing VOSviewer for visual network analysis, the research identifies central themes, examines co-authorship and institutional collaboration networks, and highlights the temporal progression of key topics. The findings reveal "entrepreneurial ecosystem" as a nexus connecting diverse research themes such as innovation, economic growth, and sustainability. Significant emphasis is placed on the integration of digital technologies and sustainability within entrepreneurial practices, reflecting shifting academic and practical priorities. The analysis of co-authorship networks shows robust collaboration among leading scholars and institutions, predominantly from Western regions, with increasing contributions from a global cohort. The study underscores the importance of incorporating diverse perspectives to fully understand the multifaceted nature of entrepreneurial ecosystems and suggests future research directions focusing on digital transformation and sustainability in entrepreneurship.

The Role of Innovation Management in Creative Economy-Based Product Development in West Java Province

This study conducts a comprehensive bibliometric analysis of the field of entrepreneurial ecosystems, mapping the evolving landscape of research from 1995 to 2024. Utilizing VOSviewer for visual network analysis, the research identifies central themes, examines co-authorship and institutional collaboration networks, and highlights the temporal progression of key topics. The findings reveal "entrepreneurial ecosystem" as a nexus connecting diverse research themes such as innovation, economic growth, and sustainability. Significant emphasis is placed on the integration of digital technologies and sustainability within entrepreneurial practices, reflecting shifting academic and practical priorities. The analysis of co-authorship networks shows robust collaboration among leading scholars and institutions, predominantly from Western regions, with increasing contributions from a global cohort. The study underscores the importance of incorporating diverse perspectives to fully understand the multifaceted nature of entrepreneurial ecosystems and suggests future research directions focusing on digital transformation and sustainability in entrepreneurship.

Temporal Dynamics of Hepatitis B Infection and Relation of Childhood Vaccination Program in Türkiye: A Longitudinal Study.

Hepatitis B is a significant infectious disease on a global scale. The implementation of vaccination programs and other preventive measures (e.g., serologic screening of blood donors) leads to lower rates of new infections with the hepatitis B virus. This study aimed to investigate and compare the evolution of hepatitis B incidence, prevalence and mortality rates along with vaccination rates in Türkiye and worldwide between 1990 and 2019. The study analyzed open datasets (the Global Burden of Disease and Our World in Data) using descriptive and joinpoint regression analysis to uncover substantial declines in hepatitis B rates from 1990 to 2019, both in Türkiye and globally. The average annual percentage change (AAPC) for incidence rates was -1.81 in Türkiye and -1.481 in the global cohort. For prevalence, the AAPC was -2.5244 in Türkiye and -1.4104 globally. The vaccination rates increased over time and remained at 95% since 2009, suggesting that vaccination efforts effectively reduced the risk of hepatitis B infection among children. This study provided important perspectives for assessing Türkiye's performance in this field and guiding future strategies.

Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20years. Limited data exist on CMMRD-associated lymphomas and their outcome. We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first. The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%. Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL.

Worldwide CTEPH Registry: Long-Term Outcomes With Pulmonary Endarterectomy, Balloon Pulmonary Angioplasty, and Medical Therapy.

The European Chronic Thromboembolic Pulmonary Hypertension registry (CTEPH), conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context. Participation in this international global registry included 34 centers in 20 countries. Between February 2015 and September 2016, 1009 newly diagnosed, consecutive patients were included and followed until September 2019. Overall, 605 patients (60%) underwent PEA and 185 (18%) underwent BPA; 76% of the 219 remaining patients not receiving mechanical intervention (ie, neither PEA nor BPA) were treated with pulmonary hypertension drugs. Oof patients undergoing PEA and BPA, 38% and 78% also received drugs for pulmonary hypertension, respectively. Median age at diagnosis was higher in the BPA and No PEA/BPA groups than in the PEA group: 66 and 69, respectively, versus 60 years. Pulmonary vascular resistance (PVR) was similar in all groups, with an average of 643 dynes/(s·cm-5). During an observation period (>3 years; ≤5.6 years), death was reported in 7%, 11%, and 27% of patients treated by PEA and BPA, and those receiving no mechanical intervention (P<0.001). In Kaplan-Meier analysis, 3-year survival was 94%, 92%, and 71% in the 3 groups, respectively. PEA 3-year survival improved by 5% from that observed between 2007 and 2012. There was no survival difference in patients receiving vitamin K antagonists and non-vitamin K oral anticoagulants (P=0.756). In Cox regression, reduced mortality was associated with: PEA and BPA in the global cohort; history of venous thromboembolism and lower PVR in the PEA group; lower right atrial pressure in the BPA group; and use of pulmonary hypertension drugs, oxygen therapy, and lower right atrial pressure, as well as functional class in the group receiving no mechanical intervention. This second international CTEPH registry reveals important improvement in patient survival since the introduction of BPA and an approved drug for pulmonary hypertension. The type of anticoagulation regimen did not influence survival. URL https://clinicaltrials.gov; Unique identifier: NCT02656238.

Proteinuria and albuminuria among a global primary CVD prevention cohort of PWH: prevalence and associated factors.

To determine baseline prevalence of proteinuria and albuminuria among REPRIEVE participants and evaluate associated risk factors. Cross sectional analysis of a baseline sample of participants from the REPRIEVE Trial. REPRIEVE is an international primary cardiovascular prevention RCT of pitavastatin calcium vs. placebo among PWH on antiretroviral therapy. A representative subset (2791 participants) had urine collected at study entry. Urine protein to creatinine ratios (uPCR) and albumin to creatinine ratios (uACR) were classified as normal, moderately increased and severely increased. These were dichotomized to Normal or Abnormal for log-binomial regression analysis. Demographic, cardiometabolic, and HIV-specific data were compared among those with normal versus abnormal results. Overall, median age 49 years, 41% female sex, 47% black or African American race, 36% had eGFR <90 mL/min/1.73 mm2. For uPCR, 27% had moderately or severely increased values. For uACR, 9% had moderately or severely increased values. In the fully adjusted model for proteinuria, female sex, older age, residence in sub-Saharan Africa or East Asia, lower BMI, lower CD4 cell count, and use of TDF were associated with abnormal values. In the fully adjusted model for albuminuria, a diagnosis of HTN was associated with abnormal values. Abnormal proteinuria and albuminuria remain common (27% and 9%) despite controlled HIV. Lower current CD4 count and TDF use were strongly associated with proteinuria. Certain modifiable comorbidities, including HTN and smoking, were associated with abnormal values. In PWH with preserved eGFR, urine measures identify subclinical kidney disease and afford the opportunity for intervention.

Outcomes of chronic myeloid leukemia patients after therapeutic failure to conventional tyrosine kinase inhibitors and asciminib.

Patients with chronic myeloid leukemia (CML) who have failed conventional tyrosine kinase inhibitors (cTKIs) and asciminib constitute a complex group of patients with few therapeutic options. A retrospective descriptive multicenter observational study was carried out including patients with CML who had presented a therapeutic failure to ≥ 2 cTKIs and asciminib, and had received or were not candidates to ponatinib. Of the 19 patients enrolled, 8 patients failed asciminib due to intolerance and 11 due to resistance. The most common strategy for intolerant patients was to initiate a previously administered cTKI (6/8) with dose adjustments or symptomatic management of adverse events (AEs). Of the patients who failed due to resistance, only patients who underwent progenitor transplantation achieved profound long-term responses. A frequent strategy was to use ponatinib (4/11) in patients previously considered non-candidates, with poor responses in patients in whom dose reductions were used, and severe AEs in patients at standard doses. In the remaining patients, cTKIs and other agents (interferon, hydroxyurea, citarabine, busulfan) were used with poor responses. Patients who progressed to advanced stages had a dismal prognosis. With a median follow-up of 11.2 months, overall survival of the global cohort was 73%; 100% for intolerant patients, 71% for resistant patients and 25% for those who discontinue asciminib in accelerated/blastic phase.

Malignant transformation and tumour recurrence in sacrococcygeal teratoma: a global, retrospective cohort study.

Sacrococcygeal teratoma (SCT) is a rare congenital tumour. The risk of malignancy and recurrence are not well defined. Previous studies are small and report differing conclusions about the timing of surgery and the duration of follow-up. We studied the risk of malignant transformation and SCT recurrence after surgery to address these gaps. This was a global retrospective cohort study. Data of consecutive SCT patients was obtained from 145 institutes in 62 countries. Malignant transformation, defined as malignancy at initial resection, malignant recurrence or death due to malignancy, and its risk factors were analysed. Of the 3612 included patients, 3407 entered analysis. Risk of malignant transformation of the initial tumour, was 3.3%, 5.1%, 10.1%, and 32.9% at age three months, six months, one year, and two years, respectively. After six years, the censored risk of malignancy (64%) did not further increase. Recurrent SCT was diagnosed in 349 (10·2%) children with 126 (36·1%) malignant recurrences. Risk factors for recurrence were Altman type II (odds ratio (OR): 1·6, 95% confidence interval (CI): 1·2-2·3), Altman type III (OR: 1·6, 95% CI: 1·2-2·3), initial immature histology (OR: 1·9, 95% CI: 1·4-2·6), and initial malignant histology (OR: 4·0, 95% CI: 2·9-5·4). The risk of malignancy at initial resection in SCT increases with age reaching a plateau at six years of age. Recurrence after resection occurred in 10% of patients and 36% of these were malignant at that time. Altman type II or type III, and immature or malignant histology were associated with recurrence. level III.

Impact of primary dressings on healing of venous leg ulcers: a French cohort study from the healthcare insurance database.

Multicomponent bandages (MCBs) are recommended by the French Authority for Health (Haute Autorité de Santé) as first-line treatment for venous leg ulcers (VLUs). A first analysis of the data collected from the French administrative healthcare database (Système National des Données de Santé (SNDS)) on 25,255 patients with a VLU supported superiority of MCBs versus short stretch bandages when considering the healing outcomes and costs associated with closure of these wounds. The aim of this study was to assess how beneficial the primary dressing (technology lipido-colloid nano-oligosaccharide factor (TLC NOSF) or control dressing group (CDG)) could be, when used in combination with MCBs in the treatment of VLUs. Data from the SNDS were collected for patients meeting the following inclusion criteria: treatment for a VLU with MCBs and with the same dressing type (TLC-NOSF or CDG) during the whole treatment period. Healing outcomes were documented on the global cohorts and propensity score-matched cohorts. The mean healthcare cost and the ecological impact were calculated for those patients healed within the study period. In total, 12,507 patients met the criteria for treatment with both MCBs and TLC-NOSF dressings (n=1134) versus MCBs and CDG (n=11,373); with 1134 and 2268 patients per group following propensity score matching. Healing outcomes were favourable for the TLC-NOSF group in the global cohort and were enhanced in the propensity score-matched cohorts. At every point of the analysis, the adjusted healing rates were significantly higher in the TLC-NOSF group than in the CDG group (p<0.001). In the propensity score-matched cohorts (n=3402), the healing rate at three months was 52% in the TLC-NOSF group versus 37% in the CDG group (p<0.001). The median healing time was 87 days versus 125.5 days in the TLC-NOSF and CDG groups, respectively (p<0.0001). TLC-NOSF dressings significantly reduced the average treatment cost per healed ulcer (€2099) by 23.7% compared with dressings without TLC-NOSF (€2751) (p<0.001), as well as the resources used. This SNDS analysis confirms, in the largest real-life study performed in VLU management, the superiority of the TLC-NOSF dressings versus those not impregnated with the NOSF compound. Better clinical outcomes associated with cost savings and a positive ecological impact support the combination of MCBs and TLC-NOSF dressings and should be considered as an optimal standard of care for the global management of VLUs. These outcomes reinforce the current positions of the international guidelines on the use of NOSF impregnated dressings (UrgoStart range; Laboratoires Urgo, France) in this pathology.

Retinoblastoma Outcomes Based on the 8th Edition American Joint Committee on Cancer Pathological Classification in 1411 Patients

PurposeTo evaluate the outcomes of retinoblastoma (RB) based on the 8th edition of the American Joint Committee on Cancer (AJCC) pathological classification in a global cohort of patients. DesignRetrospective, multicentre, intercontinental collaborative study Participants1411 patients Intervention(s)Primary enucleation with/without adjuvant chemotherapy/radiotherapy Main outcomes(s)Orbital tumor recurrence, tumor-related metastasis, tumor-related death ResultsBased on the 8th edition AJCC pathological classification, 645 (46%) eyes belonged to pT1, 164 (11%) to pT2, 493 (35%) to pT3, and 109 (8%) to pT4 categories. At a mean follow-up of 38 months (median, 35 months; <1-149 months), orbital tumor recurrence was seen in 8 (1%), 5 (3%), 22 (4%) and 25 (23%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related metastasis was seen in 7 (1%), 5 (3%), 40 (8%), and 46 (43%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related death was seen in 12 (2%), 7 (4%), 64 (13%), and 64 (59%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively. Multivariate Cox proportional hazards analysis of outcomes revealed pT category and adjuvant therapy as independent predictors of outcomes. Categories pT3b (p=0.005), pT3c (p<0.001), pT3d (p<0.001), and pT4 (p<0.001) had a greater hazard for orbital recurrence; categories pT2a (p=0.015), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related metastasis; and categories pT2a (p=0.068), pT2b (p=0.004), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related death when compared to the pT1 category. Patients who did not receive adjuvant therapy had greater hazards of orbital tumor recurrence in categories pT3b (p=0.005), pT3c (p=0.003), and pT4 (p=0.002); greater hazards of tumor-related metastasis in categories pT3a (p=0.001), pT3b (p=0.01), pT3c (p=0.001), and pT4 (p=0.007); and tumor-related death in categories pT3a (p<0.001), pT3b (p=0.009), pT3c (p=0.018), and pT4 (p<0.001) when compared to those who received adjuvant therapy. ConclusionThe 8th edition AJCC pathological classification predicts outcomes in patients undergoing primary enucleation for RB, and adjuvant therapy is associated with a lower risk of orbital recurrence, tumor-related metastasis, and tumor-related death in the pT3 and pT4 categories.

Automated Speech Analysis in Bipolar Disorder: The CALIBER Study Protocol and Preliminary Results.

Background: Bipolar disorder (BD) involves significant mood and energy shifts reflected in speech patterns. Detecting these patterns is crucial for diagnosis and monitoring, currently assessed subjectively. Advances in natural language processing offer opportunities to objectively analyze them. Aims: To (i) correlate speech features with manic-depressive symptom severity in BD, (ii) develop predictive models for diagnostic and treatment outcomes, and (iii) determine the most relevant speech features and tasks for these analyses. Methods: This naturalistic, observational study involved longitudinal audio recordings of BD patients at euthymia, during acute manic/depressive phases, and after-response. Patients participated in clinical evaluations, cognitive tasks, standard text readings, and storytelling. After automatic diarization and transcription, speech features, including acoustics, content, formal aspects, and emotionality, will be extracted. Statistical analyses will (i) correlate speech features with clinical scales, (ii) use lasso logistic regression to develop predictive models, and (iii) identify relevant speech features. Results: Audio recordings from 76 patients (24 manic, 21 depressed, 31 euthymic) were collected. The mean age was 46.0 ± 14.4 years, with 63.2% female. The mean YMRS score for manic patients was 22.9 ± 7.1, reducing to 5.3 ± 5.3 post-response. Depressed patients had a mean HDRS-17 score of 17.1 ± 4.4, decreasing to 3.3 ± 2.8 post-response. Euthymic patients had mean YMRS and HDRS-17 scores of 0.97 ± 1.4 and 3.9 ± 2.9, respectively. Following data pre-processing, including noise reduction and feature extraction, comprehensive statistical analyses will be conducted to explore correlations and develop predictive models. Conclusions: Automated speech analysis in BD could provide objective markers for psychopathological alterations, improving diagnosis, monitoring, and response prediction. This technology could identify subtle alterations, signaling early signs of relapse. Establishing standardized protocols is crucial for creating a global speech cohort, fostering collaboration, and advancing BD understanding.

Description and first insights on a large genomic biobank of lung transplantation.

The main limitation to long-term lung transplant (LT) survival is chronic lung allograft dysfunction (CLAD), which leads to irreversible lung damage and significant mortality. Individual factors can impact CLAD, but no large genetic investigation has been conducted to date. We established the multicentric Genetic COhort in Lung Transplantation (GenCOLT) biobank from a rich and homogeneous sub-part of COLT cohort. GenCOLT collected DNA, high-quality GWAS (genome-wide association study) genotyping and robust HLA data for donors and recipients to supplement COLT clinical data. GenCOLT closely mirrors the global COLT cohort without significant variations in variables like demographics, initial disease and survival rates (P > 0.05). The GenCOLT donors were 45 years-old on average, 44% women, and primarily died of stroke (54%). The recipients were 48 years-old at transplantation on average, 45% women, and the main underlying disease was chronic obstructive pulmonary disease (45%). The mean follow-up time was 67 months and survival at 5 years was 57.3% for the CLAD subgroup and 97.4% for the non-CLAD subgroup. After stringent quality controls, GenCOLT gathered more than 7.3 million SNP and HLA genotypes for 387 LT pairs, including 91% pairs composed of donor and recipient of European ancestry. Overall, GenCOLT is an accurate snapshot of LT clinical practice in France and Belgium between 2009 and 2018. It currently represents one of the largest genetic biobanks dedicated to LT with data available simultaneously for donors and recipients. This unique cohort will empower to run comprehensive GWAS investigations of CLAD and other LT outcomes.