Dependability and Prognostic Value of Biomarkers in COVID-19 Associated Rhino-Orbito- Cerebral Mucormycosis- A Long Term Ambispective Study.

COVID-19 pandemic, which has exhibited a wide clinical spectrum and an unexpected surge in mucormycosis cases, understanding various biomarkers' roles becomes pivotal. As mucormycosis leads to clinical morbidity and mortality through angioinvasion and thromboembolism, unveiling the correlation between these markers and disease progression can shed light on the reasons behind mucormycosis's emergence as an epidemic, especially following the second wave of COVID-19. This long term ambispective observational study, conducted from May 2020 to July 2023, aimed to assess specific biomarkers as predictors of severity in COVID-19-associated mucormycosis (CAM). Biomarkers measured included ESR, CRP, D-dimer, IL-8, PCT, serum ferritin, and neutrophil-lymphocyte ratio (NLR) at different time points. Data analysis employed descriptive statistics, repeated measure ANOVA, Spearman correlations, ROC curve analysis, and logistic regression. Of 290 patients, 198 completed the 2-year follow-up. Elevated baseline biomarker levels significantly decreased with treatment initiation. CRP and NLR emerged as significant predictors of severe CAM, with odds ratio 2.926 (95% CI 1.466-4.360) and 2.203 (95% CI 0.863-1.040) respectively. Factors influencing CAM progression included age, CRP, and NLR, while all biomarkers independently predicted mortality. A death prediction model using CRP, PCT, D-dimer, NLR, and IL-8 demonstrated exceptional performance, with a sensitivity of 83.1% and specificity of 100%. Elevated inflammatory markers in CAM patients showed a decline with treatment, with NLR and CRP proving crucial for predicting severity. Serial monitoring of IL-8, CRP, PCT, NLR, D-dimer, and ferritin provides insights into disease progression and prognosis. The study underscores the importance of biomarker assessment in managing CAM, especially in the context of the unpredictable clinical spectrum of COVID-19 and the subsequent mucormycosis surge. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04921-3.

Heart Transplantation and Left Ventricular Assist Devices: Long-Term Prognosis and Effects on Mental Health.

Heart transplantation and left ventricular assist devices (LVADs) have emerged as crucial interventions for end-stage heart failure, dramatically improving patient outcomes. This narrative review examines their historical context, indications, procedures, and outcomes, as well as their impact on long-term survival, quality of life, functional status, and mental health. While heart transplantation remains the optimal treatment, donor scarcity limits its application. LVADs have become a viable alternative, either as a bridge to transplantation or as destination therapy. Both interventions demonstrate similar long-term survival rates and significant improvements in health-related quality of life and functional status. However, they present distinct long-term management challenges, including immunosuppression needs for transplant recipients and device-related issues for LVAD patients. Mental health effects are considerable, necessitating psychological support and adaptive coping strategies. Complications such as infection, bleeding, and thrombosis remain concerns for both interventions. Patient selection criteria, technological advancements, and long-term management strategies are critical factors in optimizing outcomes. Future research should focus on device miniaturization, enhanced biocompatibility, and less invasive insertion techniques to further advance these therapies and improve patient care in end-stage heart failure.

Outcomes of adolescent bariatric surgery: liver disease.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing among children in the United States as pediatric obesity rates continue to rise. As such, metabolic and bariatric surgery (MBS) has become a more recognized option for treatment of obesity and has been recommended by the American Academy of Pediatrics. Although MBS is known to improve many obesity-associated comorbidities, such as hypertension and type 2 diabetes, less is known about its effect as a treatment for MASLD. This article reviewed the impact MBS has on the course of liver disease as measured by histopathology, serum markers, and radiographic imaging, among adolescents with severe obesity. Improvements were seen in alanine transaminase (ALT) liver enzymes, rates of hepatocyte steatosis, and degree of fibrosis on histopathology, and fat content in the liver on computed tomography and magnetic resonance imaging. Greater improvements in ALT were seen in patients with higher baseline values and/or a higher stage of biopsy-confirmed steatohepatitis. Biopsy-proven MASLD and metabolic dysfunction-associated steatohepatitis (MASH) have even been shown to disappear completely, but fibrosis does not completely resolve by 12 months post-MBS. To better understand the outcome of pediatric MASLD following MBS treatment, more longitudinal radiographic data and liver histology in patients with fibrosis would be informative beyond 12 months post-MBS.

Anomalous Aortic Origin of a Coronary Artery: Results from a Single Surgical Team in Spain.

OBJECTIVES: Anomalous aortic origin of a coronary artery is a rare congenital lesion in which a coronary artery arises from an anomalous location within the aorta. Anomalous aortic origin of a coronary artery has been associated with myocardial ischemia and it is considered the second most common cause of sudden cardiac arrest in young athletes. When surgical repair is indicated, surgical unroofing is the most commonly employed technique. Our objective is to describe the outcomes of our surgically treated patients. METHODS: We present a series of 16 adult patients who underwent surgical repair of anomalous aortic origin of a coronary artery. Patients were treated in three different institutions by the same surgeon. Surgical unroofing of the anomalous coronary artery was the surgical technique chosen in the majority of the patients. Follow-up was performed. RESULTS: Unroofing of an intramural anomalous coronary artery was the procedure performed in 11 patients. Three patients underwent neo-ostium creation; one patient underwent a David procedure with coronary reimplantation; and one patient was treated with coronary bypass grafting due to severe coronary atheromatous lesions. There were no perioperative deaths, and no major postoperative complications. Follow-up period was 73.8 months, the survival rate was 100%, and there were neither ischemia or heart failure reports. CONCLUSIONS: The surgical repair of anomalous aortic origin of a coronary artery by coronary unroofing or neo-ostium creation has demonstrated excellent early and late outcomes. Late survival was excellent. The follow-up period revealed no significant morbidity or complications.

Long-term treatment results of pembrolizumab monotherapy: reconsideration of immune checkpoint inhibitor monotherapy.

Objective: The extended outcomes of the KEYNOTE-024 study demonstrated a favorable 5-year overall survival (OS) rate of 31.9%. The present study investigated the outcomes of pembrolizumab monotherapy for advanced or recurrent non-small cell lung cancer (NSCLC) at our institution. Patient: The long-term outcomes of 102 patients with advanced or recurrent NSCLC treated with pembrolizumab monotherapy between March 2017 and December 2022 were retrospectively assessed. Results: This study included a total of 102 patients [mean age: 72 ± 9.6 years (range: 41-91 years), male/female=77/25; performance status (PS; 0, 1, 2, 3, 4)=49/38/15/0/0; smokers=91 (89%), non-squamous cell carcinoma/squamous cell carcinoma=66/36, PD-L1 tumor proportion score (TPS) ≥50%/1-49%=80/22, positive for EGFR mutation=5, advanced/postoperative recurrence=51/51, treatment line: first/second or later=81/21, treatment courses: median 8 (range: 1-39), objective response rate/disease control rate=44%/55%, immune-related adverse events (irAEs): 47, 5-year OS=34%]. On univariate analysis, PS, PD-L1 TPS, and irAEs were significant prognostic factors. On multivariate analysis, histology, PD-L1 TPS, and irAEs were significant prognostic factors. Conclusion: Pembrolizumab monotherapy demonstrated promising treatment outcomes for advanced or recurrent NSCLC, as evidenced by the significant association of PD-L1 TPS with irAEs and prognosis, suggesting its potential as a beneficial therapeutic option.

The Children's National Hospital Outcomes Registry: a plea for a benchmarking tool that provides longitudinal outcomes for patients and families.

Surgical advancements in paediatric cardiovascular surgery have led to improved survival rates for those patients with the most complex CHDs leading to greater numbers of patients who are living well into adulthood. Despite this new era of long-term survival, our current reporting systems continue to focus largely on using short-term postoperative outcomes as the criteria to both rate and rank hospitals. Using such limited criteria to rate and rank hospitals may mislead the intended audiences: patients and families. The goal of this article is to describe the creation of a local benchmarking report which aims to retrospectively review long-term outcomes from our single centre. This report is updated annually and published on our cardiac surgery webpage in an effort to be as transparent as possible for our patient and family communities.

Three-Year Overall Survival Outcomes and Correlative Analyses in Patients With NSCLC and High (50%-89%) Versus Very High (≥90%) Programmed Death-Ligand 1 Expression Treated With First-Line Pembrolizumab or Cemiplimab.

Introduction: Responses to first-line programmed cell death protein 1 inhibition vary among patients with metastatic NSCLC and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) greater than or equal to 50%. We previously reported improved clinical outcomes to first-line programmed cell death protein 1 inhibition in patients with metastatic NSCLC with a PD-L1 TPS of greater than or equal to 90% versus 50% to 89% in a pilot study. Here, we report the three-year survival with first-line pembrolizumab and cemiplimab in two large independent cohorts of patients with PD-L1 TPS greater than or equal to 90% versus 50% to 89% and characterize genomic and immunophenotypic differences between these PD-L1 expression groups, which were largely unknown. Methods: We analyzed three-year outcomes of the following two independent cohorts: (1) a multicenter cohort of patients from four academic centers in the United States treated with pembrolizumab and (2) EMPOWER-Lung 1, randomized, phase III trial comparing first-line cemiplimab with chemotherapy. Tumor genomic profiling and multiplexed immunofluorescence were performed to evaluate genomic and immunophenotypic correlates of very high PD-L1 expression. Results: At three years of follow-up, progression-free survival (hazard ratio [HR], 0.69; p < 0.001) and overall survival (HR, 0.70; p < 0.01) to first-line commercial pembrolizumab were significantly improved in patients with a PD-L1 TPS greater than or equal to 90% versus 50% to 89%. In the EMPOWER-Lung 1, patients assigned to the cemiplimab arm with a PD-L1 TPS greater than or equal to 90% also had significant improvements in progression-free survival (HR, 0.53; p < 0.0001) and overall survival (HR, 0.63; p = 0.007) compared with those with a PD-L1 of 50% to 89%. Tumor genomic profiling of 553 NSCLC samples revealed that mutations in STK11 and SMARCA4 were significantly more frequent in tumors with a PD-L1 TPS of 50% to 89% compared with those with a PD-L1 TPS greater than or equal to 90% (Q < 0.15), whereas BRCA2 was enriched in NSCLC samples with a PD-L1 TPS greater than or equal to 90% (Q < 0.15). Multiplexed immunofluorescence on 93 NSCLC samples identified higher intratumoral CD8+PD1+ T cells (p = 0.02) in tumors with PD-L1 TPS greater than or equal to 90% versus 50% to 89%. Conclusion: Pembrolizumab and cemiplimab were found to have long-term survival benefit and favorable genomic and immunophenotypic profile in patients with advanced NSCLC with PD-L1 TPS greater than or equal to 90% compared with TPS 50% to 89%.

Mid-term outcomes of medial metal backed and all-polyethylene unicompartmental knee arthroplasty in obese patients: a retrospective propensity-matched analysis.

BACKGROUND: This retrospective study compares the outcomes of unicompartmental medial fixed-bearing knee arthroplasty (mUKA), involving a cemented metal-backed (MB) or an all-polyethylene (AP) tibial component, performed in obese patients with a body mass index (BMI) > 30 with a follow-up of at least 5 years. METHODS: The institutional database was mined for primary mUKAs involving an MB or an AP tibial component (MB-UKA and AP-UKA groups, respectively) performed from January 2015 to August 2019. Patient demographics and patient-reported outcome measures (PROMs) were compared and a propensity score matching (PSM) analysis (1:1) using multiple variables was conducted. RESULTS: PSM analysis yielded 37 pairs of obese MB-UKA and AP-UKA patients. At 5 years, the Knee Society Function Score (KSFS) was 75.1 ± 10.6 in MB-UKA and 79.4 ± 9.1 in AP-UKA patients (p = 0.029), and the Oxford Knee Score (OKS) was 38.1 ± 4.4 in MB-UKA and 40.6 ± 5.7 in AP-UKA patients (p = 0.011). CONCLUSION: At five-year follow-up, in a matched group of obese MB-UKA and AP-UKA patients, the AP-UKA group achieved better KSFSs and OKSs. Both the AP and the MB tibial components were able to bring about a significant improvement of the most widely used PROMs.

Use of Web-Based Surveys to Collect Long-Term Pediatric Outcomes in Patients With Twin-Twin Transfusion Syndrome Treated With Fetoscopic Laser Photocoagulation: Observational Study.

Background: In the United States, patients with monochorionic diamniotic twins who undergo in utero fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS) may travel great distances for care. After delivery, many parents cannot return to study sites for formal pediatric evaluation due to geographic location and cost. Objective: The aim of this study was to collect long-term pediatric outcomes in patients who underwent FLP for TTTS. Methods: We assessed the feasibility of using a web-based survey designed in REDCap (Research Electronic Data Capture; Vanderbilt University) to collect parent-reported outcomes in children treated for TTTS at a single center during 2011-2019. Patients with ≥1 neonatal survivor were invited via email to complete 5 possible questionnaires: the child status questionnaire (CSQ); fetal center questionnaire (FCQ); Ages & Stages Questionnaires, Third Edition (ASQ-3); Modified Checklist for Autism in Toddlers, Revised With Follow-Up (M-CHAT-R/F); and thank you questionnaire (TYQ). The R programming language (R Foundation for Statistical Computing) was used to automate survey distribution, scoring, and creation of customized reports. The survey was performed in 2019 and repeated after 12 months in the same study population in 2020. Results: A total of 389 patients in 26 different states and 2 international locations had an email address on file and received an invitation in 2019 to complete the survey (median pediatric age 48.9, IQR 1.0-93.6 months). Among surveyed mothers in 2019, the overall response rate was 37.3% (145/389), and the questionnaire completion rate was 98% (145/148), 87.8% (130/148), 71.1% (81/100), 86.4% (19/22), and 74.3% (110/148) for the CSQ, FCQ, ASQ-3, M-CHAT-R/F, and TYQ, respectively. In 2020, the overall response rate was 57.8% (56/97), and the questionnaire completion rate was 96.4% (54/56), 91.1% (51/56), 86.1% (31/36), 91.7% (11/12), and 80.4% (45/56) for the CSQ, FCQ, ASQ-3, M-CHAT-R/F, and TYQ, respectively. Conclusions: This is the first study to use both REDCap and computer automation to aid in the dissemination, collection, and reporting of surveys to collect long-term pediatric outcomes in the field of fetal medicine.

Developing machine learning models for personalized treatment strategies in early breast cancer patients undergoing neoadjuvant systemic therapy based on SEER database.

This study aimed to compare the long-term outcomes of breast-conserving surgery plus radiotherapy (BCS + RT) and mastectomy in early breast cancer (EBC) patients who received neoadjuvant systemic therapy (NST), and sought to construct and authenticate a machine learning algorithm that could assist healthcare professionals in formulating personalized treatment strategies for this patient population. We analyzed data from the Surveillance, Epidemiology, and End Results database on EBC patients undergoing BCS + RT or mastectomy post-NST (2010-2018). Employing propensity score matching (PSM) to minimize potential biases, we compared breast cancer-specific survival (BCSS) and overall survival (OS) between the two surgical groups. Additionally, we trained and validated six machine learning survival models and developed a cloud-based recommendation system for surgical treatment based on the optimal model. Among the 13,958 patients, 9028 (64.7%) underwent BCS + RT and 4930 (35.3%) underwent mastectomy. After PSM, there were 3715 patients in each group. Compared to mastectomy, BCS + RT significantly improved BCSS (p < 0.001) and OS (p < 0.001). Prognostic variables associated with BCSS were utilized to develop machine learning models. In both the training and validation cohorts, the random survival forest (RSF) model demonstrated superior predictive performance (0.847 and 0.795), not only outperforming other machine learning models, including Rpart (0.725 and 0.707), Xgboost (0.762 and 0.727), Glmboost (0.748 and 0.788), Survctree (0.764 and 0.766), and Survsvm (0.777 and 0.790), but also outperforming the classical COX model (0.749 and 0.782). Lastly, a web-based prediction tool was built to facilitate clinical application [ https://jhren.shinyapps.io/shinyapp1 ]. After adjusting other confounders, BCS + RT was associated with improved outcomes in patients with EBC after NST, compared to those who underwent mastectomy. Moreover, the RSF model, a reliable tool, can predict long-term outcomes for patients, providing valuable guidance for operative methods and postoperative follow-up.

The Price We Pay for Progression in Shock Care: Economic Burden, Accessibility, and Adoption of Shock-Teams and Mechanical Circulatory Support Devices.

PURPOSE OF REVIEW: Cardiogenic shock (CS) is associated with high in-hospital and long-term mortality and morbidity that results in significant socio-economic impact. Due to the high costs associated with CS care, it is important to define the short- and long-term burden of this disease state on resources and review strategies to mitigate these. RECENT FINDINGS: In recent times, the focus on CS continues to be on improving short-term outcomes, but there has been increasing emphasis on the long-term morbidity. In this review we discuss the long-term outcomes of CS and the role of hospital-level and system-level disparities in perpetuating this. We discuss mitigation strategies including developing evidence-based protocols and systems of care, improvement in risk stratification and evaluation of futility of care, all of which address the economic burden of CS. CS continues to remain the pre-eminent challenge in acute cardiovascular care, and a combination of multi-pronged strategies are needed to improve outcomes in this population.

Long-term outcomes of left bundle branch area pacing compared with right ventricular pacing in TAVI patients.

BACKGROUND: New-onset permanent pacemaker implantation (PPMI) is still a common complication after transcatheter aortic valve implantation (TAVI) with adverse clinical outcomes. OBJECTIVE: The purpose of this study was to investigate whether left bundle branch area pacing (LBBAP) improves long-term clinical results compared with traditional right ventricular pacing (RVP) in patients requiring PPMI after TAVI. METHODS: A total of 237 consecutive patients undergoing RVP (N = 117) or LBBAP (N = 120) after TAVI were retrospectively included. Long-term outcomes, including all-cause death, heart failure rehospitalization (HFH), and left ventricular ejection fraction (LVEF) change compared to baseline, were obtained until 5 years post-TAVI. RESULTS: The mean age of the overall population was 74 years, with a mean surgical risk score of 4.4%. The paced QRS duration was significantly longer in the RVP group compared with the LBBAP group (151 ± 18 vs 122 ± 12 ms; P < .001). No difference was found between the 2 groups in all-cause death (13.7% vs 13.3%; adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.37-1.58; P = .466) or the composite endpoint of death and HFH (29.9% vs 19.2%; adjusted HR, 1.22; 95% CI, 0.70-2.13; P = .476); however, the risk of HFH was significantly higher in the RVP group at 5 years after TAVI (21.4% vs 7.5%; adjusted HR, 2.26; 95% CI, 1.01-5.08; P = .048). There was greater improvement of LVEF over time in the LBBAP group (P = .046 for LVEF changes over time between groups). CONCLUSIONS: LBBAP improved long-term clinical outcomes compared with RVP in patients undergoing PPMI after TAVI in terms of less HFH and better LVEF improvement.

Long-Term Outcomes of Allergic Bronchopulmonary Aspergillosis and Aspergillus Colonization in Children and Adolescents with Cystic Fibrosis.

Observational studies indicate that Aspergillus colonization and allergic bronchopulmonary aspergillosis (ABPA) in people with cystic fibrosis (CF) are associated with poorer lung health and increased disease severity. We performed a longitudinal observational cohort study to analyse long-term outcomes of Aspergillus colonization and ABPA in children with CF. Anonymised UK CF Registry data from 2009 to 2019 for patients aged 8-17 years in 2009-2010 were collected. For the baseline cohort analysis, patients were classified based on the presence of Aspergillus colonization and ABPA in 2009 and/or 2010. For the longitudinal analysis, patients were categorised according to annual Aspergillus colonization and ABPA status. Comparisons made were (1) Aspergillus positive vs. negative; (2) excluding those with ABPA: Aspergillus positive vs. negative; and (3) ABPA positive vs. negative. Primary outcome was percentage predicted FEV1 decline and secondary outcomes included BMI decline, mortality, lung transplant, and IV antibiotic use. Of the 1675 children, 263 had Aspergillus colonization in the baseline cohort, 260 were diagnosed with ABPA, and 80 had both. Baseline cohort analysis showed significantly lower lung function (p < 0.0001) and increased antibiotic treatment (p < 0.001) in those with Aspergillus colonization and in those with ABPA. Longitudinal analysis showed ABPA was associated with increased decline in lung function (p < 0.00001) and BMI (p < 0.00001). Aspergillus colonization was associated with increased decline in BMI (p = 0.005) but not lung function (p = 0.30). ABPA was associated with increased decline in long-term lung function and BMI in children and young people with CF. Aspergillus colonization was associated with lower lung function at baseline, but no increased rate of decline was observed long-term.

Impact of Newly Diagnosed Left Bundle Branch Block on Long-Term Outcomes in Patients with STEMI.

Background/Objectives: This study assessed the long-term prognostic implications of newly developed left bundle branch block (LBBB) in patients with ST-elevation myocardial infarction (STEMI) and a single coronary lesion, following primary percutaneous coronary intervention (PCI). Methods: Among 3526 patients admitted with acute myocardial infarction between January 2011 and December 2013, 42 were identified with STEMI, a single coronary lesion, and newly diagnosed LBBB. A control group of 42 randomly selected STEMI patients without LBBB was also included. All participants were prospectively evaluated with a median follow-up duration of 9.4 years. Demographic, clinical, and laboratory data were analyzed to assess the impact of LBBB on long-term outcomes. Results: The baseline characteristics were similar between the groups. The STEMI with new LBBB group had significantly higher rates of new myocardial infarction, revascularization, and mortality, highlighting the severe prognostic implications and elevated risk for adverse outcomes compared to STEMI without LBBB. The multivariate Cox regression analysis demonstrated that the presence of LBBB (HR: 2.15, 95% CI: 1.28-3.62, p = 0.003), lower LVEF (HR: 1.45, 95% CI: 1.22-1.72, p < 0.001), and longer pain-to-admission time (HR: 1.32, 95% CI: 1.09-1.61, p = 0.008) were significant independent predictors of adverse outcomes. Conclusions: Newly acquired LBBB in STEMI patients is associated with poorer long-term outcomes. Early identification and management of factors such as reduced LVEF and timely hospital admission, specifically in patients with new-onset LBBB, can improve prognosis.

Long-Term Outcomes in Patients Managed with the EndurantTM Endograft under Elective Setting.

Background/Objectives: Device selection during endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs) remains an important issue for ensuring endograft durability. This study evaluated the early and follow-up outcomes of elective EVAR with the Endurant platform. Methods: A single-center retrospective analysis was conducted including consecutive elective EVAR procedures with the Endurant II/IIs (2008 to 2024) device. Primary outcomes were technical success, mortality and major complications at 30 days. Survival, endoleak I/III and freedom from reintervention were secondary outcomes. Cox proportional hazards models were employed for risk-adjusted follow-up outcomes. Results: In total, 361 patients were included (72.7 ± 7 years; 96% males; mean AAA diameter 62 ± 14 mm); 92% received a bifurcated device, and 89% conformed to the instructions for use. Technical success was 99.7%. Intra-operative adjunctive procedures included 4.4% proximal cuffs and 1.7% endoanchors. The thirty-day mortality rate was 0.6%, and the major complication rate was 4.1%. Survival was 81% (SE 4.8%), 72% (SE 6.4%) and 52% (SE 9.2%) at 4, 6 and 8 years, with aneurysm-related mortality at 1.7%. Freedom from endoleak Ia was 76% (SE 7.3%) at 6 years, freedom from endoleak Ib was 79% (SE 7.4%) at 7 years and freedom from endoleak III was 94% (SE 3.7%) at 5 years. Freedom from reintervention was 71% (SE 6.1%) and 55% (SE 7.9%) at 5 and 7 years, respectively. No device-related co-factor affected long-term outcomes. Conclusions: Endurant II/IIs endograft is a safe and effective EVAR solution with excellent early outcomes and low long-term aneurysm-related mortality. The need for reintervention in the long term affected less than 50% of cases.

Revisiting PPAR agonists: novel perspectives in the treatment of primary biliary cholangitis.

INTRODUCTION: In primary biliary cholangitis (PBC), approximately 40% of the patients respond incompletely to first-line treatment with ursodeoxycholic acid (UDCA), resulting in a poorer prognosis. Although obeticholic acid (OCA) is approved as a second-line therapy, it is not well-tolerated by patients with significant itching or advanced cirrhosis. Peroxisome proliferator-activated receptor (PPAR) agonists, including fibrates traditionally known as antihyperlipidemic agents, have emerged as potent alternatives for treating PBC patients with an incomplete response to UDCA. AREAS COVERED: This article provides a detailed overview of the mechanisms of PPAR agonists and evaluates their efficacy and adverse events, focusing on findings from recent phase III clinical trials. EXPERT OPINION: PPAR agonists are significant alternatives in the treatment of PBC, showing the potential to enhance biochemical responses, reduce mortality, and alleviate pruritus. Long-term outcomes for PBC patients, particularly those with advanced disease, and longitudinal data on the antipruritic effects of PPAR agonists require further investigation. Combining PPAR agonists with other treatments and advancing personalized approaches may enhance therapeutic efficacy and patient outcomes. This study provides future perspectives on the roles of PPAR agonists in PBC management.

15 Years of Vacuum Bell Therapy for Pectus Excavatum: Long-term Outcomes and Influencing Factors.

BACKGROUND: Long-term results and factors affecting outcomes of vacuum bell therapy for pectus excavatum are relatively unknown. METHODS: We conducted a retrospective study on patients (<18y) treated with vacuum bell therapy between May 2008 and October 2021. Primary outcome was treatment success; secondary outcomes were analysis of daily time spent on treatment, treatment duration, complications, long-term follow-up, treatment for patients awaiting a Nuss procedure, treatment for female patients, and factors affecting outcomes. RESULTS: Of 259 patients treated with vacuum bell therapy, 18.9% (n = 49/259) were still being treated, 17.4% (n = 45/259) were lost to follow-up and 63.7% (n = 165/259) completed treatment, with a 52.1% (n = 86/165) success rate. Median follow-up was 64.0 months (interquartile range 48.0-87.0). More time spent daily on vacuum bell therapy, total treatment duration, and overnight use led to a higher success rate (P = 0.002, P < 0.001, P < 0.001 resp.). Complications (22.8%, n = 59/259) were minor, recurrence occurred in 2.3% (n = 2/86) of patients. Of the patients treated while awaiting a Nuss procedure, 26.7% (n = 4/15) no longer required the Nuss procedure. Breast growth made 39.3% (n = 11/28) of female patients quit treatment. Deeper deformities (P = 0.02, P = 0.009), flexible chest wall (P = 0.007) and symptomatic pectus excavatum (P = 0.02) resulted in lower success rates. CONCLUSIONS: Vacuum bell therapy is successful in up to 52.1% of patients. Overnight vacuum bell use and treatment while awaiting a Nuss procedure should be encouraged. Older patients with a stiff chest wall can be successfully treated with prolonged treatment. For female patients watchful waiting or early treatment, to prevent challenges during breast growth, is preferred. LEVEL OF EVIDENCE: Level II.

Transanal Endorectal Pull-Through for Hirschsprung's Disease: Complications and Lessons from Our Practice and the Literature.

BACKGROUND/OBJECTIVES: Hirschsprung's disease (HD) is a congenital disorder characterised by the absence of ganglion cells in the distal bowel, resulting in functional obstruction. The transanal endorectal pull-through (TEPT) procedure, a minimally invasive approach, aims to treat HD by removing the aganglionic segment. This study assessed the feasibility, safety, and efficacy of single-stage TEPT in paediatric patients, focusing on postoperative complications, bowel function, and quality of life. METHODS: A retrospective cohort study was conducted on 150 children who underwent single-stage TEPT from January 2005 to December 2023 at the Medical University of Gdansk. Data were collected from medical records, including demographics, preoperative assessments, surgical details, postoperative management, and follow-up outcomes. Statistical analyses were performed using Microsoft Excel 365 and the programming language Python 3.12. The mean age at surgery was 13 months, with a male-to-female ratio of 2.75:1. The mean operative time was 129 min, and the mean hospital stay was seven days. RESULTS: Postoperative complications included anastomotic leak (4%), wound infections (15%), and enterocolitis (26%). Redo surgeries were required in 18% of cases due to persistent constipation and obstructive symptoms. This article includes a comprehensive review of the literature. CONCLUSIONS: TEPT demonstrates a favourable safety profile and efficacy in treating HD, though significant concerns include complications such as enterocolitis and the need for additional surgeries. Surgical expertise and thorough preoperative and postoperative management are crucial to optimising patient outcomes.

"Gastrointestinal Quality of Life After Congenital Duodenal Obstruction Repair: A Nationwide Long-term Follow-up Study".

BACKGROUND: Congenital duodenal obstruction (CDO) is one of the most common gastrointestinal congenital anomalies. Still, patient-reported long-term results are limited. The aims of this study were to evaluate the long-term gastrointestinal quality of life (QoL), generic QoL, patient-reported scar appearance, and reinterventions after CDO repair. METHODS: Patients who underwent surgery for CDO in Norway from 1995 to 2020 were invited to answer the validated questionnaires PedsQL and PedsQL gastrointestinal symptom scale and a study-specific questionnaire on general health and scar assessment. Parent-proxy reports were used for patients <12 years and patients with cognitive impairment. Scores were compared with an American and Norwegian control group for gastrointestinal and generic QoL, respectively. RESULTS: Of 186 eligible patients, eight were deceased, 25 had unretrievable contact information, and 79 did not respond. There were no significant differences between included (n = 74) and not included (n = 112) patients regarding baseline data. The mean follow-up time was 13.3 (SD = 6.6) years. Patients with CDO had significantly lower overall gastrointestinal QoL than controls (85.9 versus 90.0, p = 0.010). The most common symptoms were gas/bloating, constipation, food/drink limits, and reflux. Generic QoL was similar between the CDO population and controls (84.4 versus 85.3, p = 0.530). Twenty-one (28 %) patients had some degree of pain and/or concern related to the surgical scar. Nine (12 %) patients had reoperations related to the CDO repair; four due to adhesive small bowel obstruction. CONCLUSION: A notable portion of patients report troublesome gastrointestinal symptoms and cosmetic concerns regarding their surgical scar after CDO repair. Even so, generic QoL was good. LEVEL OF EVIDENCE: IV.