Search Results (2,473)

India’s population complexity presents varied challenges in genetic research, and while facilities have gained traction in tier-1 and -2 cities, reliance on international collaborations often delays such investigations. COVID-19 further exacerbated the issues with such sample sharing. Congenital Hyperinsulinism (CHI) is a rare genetic disorder of pancreatic β-cells causing hypoglycaemia in children due to abnormal insulin secretion. Given India’s high birth rate and consanguineous populations, annual CHI cases are estimated to be around up to 10,000, with up to 50% having unexplained genetic causes. Diffuse or atypical lesions in such patients often necessitate near-total-pancreatectomy, risking pancreatic exocrine insufficiency and diabetes, requiring lifelong therapy. Also, novel genetic variations complicate accurate diagnosis, risk assessment, and counselling, emphasising the need for rapid genetic assessment to prevent neurological injuries and inform treatment decisions. Despite significant efforts at many institutes, there are no dedicated organisations for CHI in India. With the implementation of the National Policy for Rare Diseases 2021, we plan to form a non-profit organisation, “Congenital Hyperinsulinism India Association (CHIA)”, comprising paediatric endocrinologists, paediatricians, geneticists, and independent researchers. The aims of this association are to generate a national database registry of patients, formulate a parent support group and CHIA consortium, design patient information leaflets, as well as foster genomic collaborations and promote clinical trials. Such steps will help sensitise the health authorities and policy makers, urging them to improve the allocation of health budgets for rare diseases, as well as empower patients and their families, contributing towards a better quality of life. Full article

Background: The human brain relies on complex synaptic communication regulated by key genes such as SYNGAP1. SYNGAP1 encodes the GTPase-Activating Protein (SYNGAP), a critical synaptic plasticity and neuronal excitability regulator. Impaired SYNGAP1 function leads to neurodevelopmental disorders (NDDs) characterized by intellectual disability (ID), epilepsy, and behavioral abnormalities. These variants disrupt Ras signaling, altering AMPA receptor transport and synaptic plasticity and contributing to cognitive and motor difficulties. Despite advancements, challenges remain in defining genotype–phenotype correlations and distinguishing SYNGAP1-related disorders from other NDDs, which could improve underdiagnosis and misdiagnosis. Brain Gene Registry: The Brain Gene Registry (BGR) was established as a collaborative initiative, consolidating genomic and phenotypic data across multiple research centers. This database allows for extensive analyses, facilitating improved diagnostic accuracy, earlier interventions, and targeted therapeutic strategies. The BGR enhances our understanding of rare genetic conditions and is critical for advancing research on SYNGAP1-related disorders. Conclusions: While no FDA-approved treatments exist for SYNGAP1-related disorders, several therapeutic approaches are being investigated. These include taurine supplementation, ketogenic diets, and molecular strategies such as antisense oligonucleotide therapy to restore SYNGAP1 expression. Behavioral and rehabilitative interventions remain key for managing developmental and cognitive symptoms. Advancing research through initiatives like the BGR is crucial for refining genotype–phenotype associations and developing precision medicine approaches. A comprehensive understanding of SYNGAP1-related disorders will improve clinical outcomes and patient care, underscoring the need for continued interdisciplinary collaboration in neurodevelopmental genetics. Full article

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced non-small cell lung cancer (NSCLC). Emerging evidence suggests a potential association between elevated body mass index (BMI) and enhanced ICI efficacy, yet this relationship remains inconclusive and warrants further investigation. This study aims to evaluate the impact of BMI on treatment efficacy and survival outcomes in advanced NSCLC patients treated with first-line ICI therapy. Methods: A retrospective study was conducted at a multi-center registry to evaluate the impact of baseline BMI on overall survival (OS) and progression-free survival (PFS) in patients with stage IV NSCLC who received first-line ICI therapies. Treatment regimens included pembrolizumab or the combination of ipilimumab and nivolumab, administered either as monotherapy or in combination with chemotherapy, at the oncology department between January 2018 and December 2023. BMI was categorized according to the World Health Organization (WHO) classification, and OS and PFS were evaluated using Kaplan–Meier survival analysis and the Cox proportional hazards regression model. Results: Among 346 patients, 12.72% were underweight, 45.38% normal weight, 29.19% overweight, and 12.72% obese. Overweight and obese patients were more likely to receive pembrolizumab (p = 0.039) and less likely to undergo chemotherapy (p = 0.012). No significant differences in median overall survival (OS, log-rank: p = 0.155) or progression-free survival (PFS, log-rank: p = 0.370) were observed across BMI categories. However, differences emerged upon further analysis of PD-L1 levels (OS, log-rank: p = 0.029; PFS, log-rank: p = 0.044), additional chemotherapy (OS, log-rank: p = 0.009; PFS, log-rank: p = 0.021), type of immune checkpoint inhibitor (OS, log-rank: p < 0.001; PFS, log-rank: p < 0.001), and histologic diagnosis (OS, log-rank: p = 0.011; PFS, log-rank: p = 0.003). Conclusions: BMI was not an independent predictor of survival outcomes in advanced NSCLC treated with ICI. Incorporating BMI with other patient-specific factors into personalized immunotherapy strategies highlights the importance of tailored approaches to improve patient care and clinical outcomes. Full article

Background/Objectives: The present study updates the Spanish registry of patients with urea cycle disorders (UCD), originally established in 2013, to provide comprehensive epidemiological data and evaluate the impact of therapeutic strategies and newborn screening (NBS) on clinical outcomes. Methods: This retrospective, multicenter study focuses on 255 Spanish UCD patients. It includes all living and deceased cases up to February 2024, analyzing demographic, clinical, and biochemical variables. Results: The incidence of UCD in Spain over the past decade was 1:36,063 births. The most common defects were ornithine transcarbamylase deficiency (OTCD) and argininosuccinate synthetase deficiency. Early-onset (EO) cases comprised 32.7%, and 10.6% were diagnosed through NBS. Global mortality was 14.9%, higher in carbamoylphosphate synthetase 1 deficiency (36.8%) and male OTCD patients (32.1%) compared to other defects (p = 0.013). EO cases presented a higher mortality rate (35.8%) than late-onset (LO) cases (7.1%) (p < 0.0001). The median ammonia level in deceased patients was higher at 1058 µmol/L (IQR 410–1793) than in survivors at 294 µmol/L (IQR 71–494) (p < 0.0001). Diagnosis through NBS improved survival and reduced neurological impairment compared to symptomatic diagnosis. Neurological impairment occurred in 44% of patients, with worse neurological outcomes observed in patients with argininosuccinate lyase deficiency, arginase 1 deficiency, hyperornithinemia-hyperammonemia-homocitrullinuria, EO presentations, pre-2014 diagnosis, and patients with higher levels of ammonia at diagnosis. Among transplanted patients (20.6%), survival was 95.2%, with no significant neurological differences compared to non-transplanted patients. Conclusions: This updated analysis highlights the positive impact of NBS and advanced treatments on mortality and neurologic outcomes. Persistent neurological challenges underscore the need for further therapeutic strategies. Full article

Background: Biosimilars represent a fundamental advancement in global healthcare, offering significant cost containment while maintaining both therapeutic efficacy and safety in the management of chronic diseases. The cost savings generated by adopting biosimilars could be reinvested to foster innovation in the healthcare sector and enhance patient access to advanced therapies. Methods: A comprehensive analysis was conducted within an Italian healthcare organization which, through its hospital network, serves over 3.5 million individuals. Usage patterns, expenditure, and patient coverage for the principal biosimilar agents across various therapeutic areas were examined. Data were extracted from institutional registries, and a year-over-year comparison from 2022 to 2024 was performed to evaluate trends in consumption, biosimilar adoption among treatment-naïve patients, incurred costs, potential and actual savings, as well as therapeutic switching profiles. Results: The analysis revealed a marked shift towards biosimilar formulations for the majority of the evaluated biological agents between 2022 and 2024. However, for certain active substances, a reduced market penetration of biosimilars was observed, and critical issues persist that will necessitate future interventions. Conclusions: The results demonstrate a consistent upward trajectory in biosimilar adoption, underscoring significant progress toward their integration into routine clinical practice—a transition that has generated substantial savings over the three-year period considered. Assuming a complete transition to biosimilars, the cumulative potential savings over the three-year period would amount to EUR 7,172,372.99 in 2022, EUR 6,209,289.05 in 2023, and EUR 23,536,824.05 in 2024. This trend aligns with strategic objectives to enhance the sustainability of the Italian National Health Service (SSN) through optimized resource allocation and improved patient access. Full article

Background/Objectives: The objective was to compare the results of segmentectomy and lobectomy in the treatment of c-stage IA lung cancer in terms of tumor recurrence and 5-year survival. Methods: An observational study was performed using 3533 patients included in the registry of the Spanish VATS Group (GEVATS) of the Spanish Society of Thoracic Surgery (SECT) between 2016 and 2018. A total of 1004 lobectomies and 83 segmentectomies in c-stage IA were selected. Two comparable groups were selected through 2:1 propensity score matching with patient-, tumor- and surgery-related variables, leaving 166 lobectomies and 83 segmentectomies. Tumor recurrence was analyzed by Fisher’s test and overall, cancer-specific, recurrence-free and disease-free survival by Kaplan-Meier and Log-rank tests. Results: Overall recurrence was 23.7% in both groups, with a predominance of locoregional recurrence in segmentectomy (16.2% vs. 11.2%) and distant recurrence in lobectomy (12.5% vs. 7.5%). There was no difference between the two groups in any of the survival types. Overall survival at 5 years was 73.5% (95% CI: 65.5–82.4%) in the lobectomy group vs. 73.1% (95% CI: 60.1–88.9%) in the segmentectomy group. Conclusions: Anatomic segmentectomy may be a valid option in the treatment of c-stage IA lung cancer since the recurrence and long-term survival outcomes compared to lobectomy are equivalent. Full article

Atypical teratoid rhabdoid tumors are rare embryonal tumors of the nervous system mainly seen in very young children with aggressive behavior and dismal prognosis when treated with conventional chemotherapy only. More recent multimodal strategies combining, variably, high dose chemotherapy, radiotherapy and or intrathecal chemotherapy have led to some stride in survival. We present the results of the most recent clinical trials and registry data for patients treated with these multimodal approaches with survival ranging from 37.1% to 88.9%. We review the current consensus of the molecular characterization of these tumors into 3 subgroups (ATRT-TYR, ATRT-SHH and ATRT-MYC) and discuss the potential clinical impact of molecular subgrouping on survival. We explore other therapeutic tools including intrathecal chemotherapy and maintenance and possible new targeted agents for patients failing multimodal strategies Full article

Background: A subset of patients with locally advanced or metastatic bladder cancer (la/mBC) do not receive systemic oncological treatment. The reasons for refraining from systemic treatment are poorly investigated, as are the characteristics of patients who turn out to be long-term survivors despite lack of treatment. Methods: This retrospective observational cohort study included patients with registration compatible with la/mBC who did not undergo systemic treatment. They were seen at a single tertiary university hospital covering one of 5 Danish regions in the study period from 1 January 2012 until 31 December 2022. Patients were identified through a coding system, and detailed patient information was obtained in the electronic medical records. Results: The initial study population consisted of 472 patients registered with la/mBC according to codes in the patient registries but with no registration of systemic oncological treatment. Out of the total cohort, 159 patients were registered correctly, while the rest of the population were excluded due to misclassification, as 10.8% did not have la/mBC and 55.5% had received oncological treatment. Among correctly registered patients, the median overall survival was 2.6 months (95% CI 0.26; 4.94) from being diagnosed with la/mBC. The most common reasons for lack of treatment were poor general condition (74.2%), patient preference (19.5%), and poor renal function (11.9%). Conclusions: Our study found that a significant amount of patients in a cohort of suspected la/mBC not undergoing treatment either received oncological treatment or did not have la/mBC, demonstrating a misclassification in the system. This should be taken into consideration when evaluating data about survival time for this patient group. The poorest survival of untreated la/mBC is associated with a high tumor burden and specifically liver metastasis. Full article

Background: Cardiogenic shock (CS) is a frequent presentation of anterior ST-elevation myocardial infarction (STEMI); however, data regarding disease progression and outcomes in inferior STEMI complicated by CS are scarce. The present study aims to analyze the prevalence, patterns of disease progression, and outcomes of inferior STEMI-CS. Methods: The INSTINCT (Inferior ST-elevation myocardial Infarction complicated by Cardiogenic shock) Registry retrospectively included consecutive patients who developed CS following inferior STEMI treated at three centers in Italy from 2015 to 2023. Data regarding CS stage according to the Society of Cardiovascular Angiography and Interventions (SCAI) upon diagnosis of shock and during disease progression and in-hospital outcomes were collected. Patients were defined “worsening” (WPs) if the SCAI stage increased. Results: A total of 130 patients developed CS after inferior STEMI and were included in the analysis, the mean age was 69.8 ± 12.4 years, and 31.5% were female. The rate of in-hospital mortality was 22.3%; predictors of in-hospital mortality were cardiopulmonary resuscitation (CPR) > 20 min or refractory cardiac arrest (CA) (OR [CI]: 9.67 [3.17–29.51]), persistently low systolic blood pressure (SBP) (OR [CI]: 12.91 [2.47–68.82]), and increase in lactates (OR [CI]: 3.53 [1.42–7.87]) during medical management. Twenty (15.4%) patients experienced worsening CS; WPs had a significantly higher rate of in-hospital mortality (13 [65%] vs. 15 [13.6%], p < 0.001), major bleeding (4 [20%] vs. 7 [6.4%], p = 0.044), and mechanical circulatory support weaning failure (7 [35%] vs. 3 [2.7%], p = 0.032). Conclusions: The in-hospital mortality rate of inferior STEMI complicated by CS was 22.3%. Predictors of in-hospital mortality included prolonged CPR, persistently low SBP, and elevated lactates. Progression through SCAI stages was rare but associated with significantly higher mortality and complication rates. Full article

Chronic hepatitis B is linked with considerable liver-related morbidity and mortality globally. Human leukocyte antigen (HLA) polymorphisms affect the susceptibility and outcome of many immune-mediated diseases and infections. Our aim was to study the impact of HLA alleles on HVB-infected individuals in a Greek population. In total, 107 patients with chronic HBV infection (cHBV group) and 101 with spontaneous clearance (SC-group) of hepatitis B surface antigen (HBsAg) were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci by single-specific primer polymerase chain reaction (PCR-SSP). The HLA alleles’ frequencies were compared between the two patient groups and healthy individuals from the North Greece Bone Marrow Donor Registry (14506 samples). We found a significantly increased frequency of HLA-C*01 and HLA-DRB1*16 alleles in the cHBV group versus the SC-group. The frequency of HLA-A*01, HLA-B*08, HLA-C*01, HLA-C*08, HLA-DRB1*03, and HLA-DQB1*05 alleles was significantly higher in cHBV patients versus healthy individuals, while the frequency of the HLA-B*38 allele was significantly lower. Our study showed an association of specific HLA alleles with either susceptibility or protection against chronic HBV infection. Full article

Objective: We aimed to characterize the impact of body mass index (BMI) on stroke in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). Methods: We queried the Extracorporeal Life Support Organization registry for patients receiving ECPR (2020–2024). Patients were categorized into five BMI groups: underweight (<18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), class 1 obesity (30–34.9 kg/m²), and class 2 obesity or above (≥35 kg/m²). A generalized additive model (GAM) analysis was used to identify the BMI range with the greatest stroke risk. Multivariable regression was used to compare odds of stroke between standard BMI groups and normal weight. Propensity score matching was used to compare stroke and mortality between normal weight and the BMI group with the highest predicted stroke risk. Results: Of 6390 patients (median age = 57.5, 68.6% male), 470 (7.4%) had a stroke during ECMO support (4.5% ischemic; 3.4% hemorrhagic). A total of 9.6% (n = 131) of class 1 obesity patients experienced stroke compared with 6.6% (n = 111) of normal weight, 6.9% (n = 79) of class 2 obesity or above, 6.9% (n = 143) of overweight, and 5.4% (n = 6) of underweight patients (p = 0.01). The GAM analysis showed a highest predicted stroke risk for class 1 obesity patients (n = 1366), which was confirmed by multivariable regression (adjusted odds ratio (aOR) = 1.63, 95%CI = 1.01–2.62, p = 0.045). After propensity matching (n = 357 each), class 1 obesity was associated with ischemic (aOR = 2.01, 95%CI = 1.02–4.08, p = 0.047) but not hemorrhagic stroke. Odds of hospital mortality were higher in both class 1 and 2 obesity patients compared with normal weight. Conclusions: Class 1 obesity was associated with increased odds of ischemic but not hemorrhagic stroke compared with normal weight patients. Full article

Background/Objectives: The diagnosis of hepatocellular carcinoma (HCC) mainly relies on imaging, with biopsy reserved for cases where imaging results are inconclusive. While biopsy offers histological confirmation and can guide treatment decisions, its impact on survival outcomes in HCC patients remains uncertain. This study aimed to examine biopsy practices and evaluate their effects on survival rates in HCC patients. Methods: We analyzed data from 18,304 HCC patients in the Korean Primary Liver Cancer Registry from 2008 to 2019. We compared overall survival (OS) and transplant-free survival (TFS) between patients who underwent a biopsy and those diagnosed solely based on imaging. Results: From 2008 to 2019, liver biopsy rates varied, reaching a peak of 12.44% in 2009 and declining to 8.18% in 2012, with the majority of patients (90.3%) diagnosed through imaging. Trans-arterial chemoembolization was the most common treatment overall (40.5%), especially in the non-biopsy group. Sorafenib use increased significantly in both groups after 2015. Patients who underwent biopsy had lower OS (43.1 ± 1.29 months) and TFS (42.45 ± 1.28 months) compared to those diagnosed via imaging (OS: 54.5 ± 0.48 months, TFS: 52.57 ± 0.47 months, p < 0.001 for both). However, Cox regression analysis indicated that biopsy was not a significant risk factor for OS (HR: 1.021, p = 0.502) or TFS (HR: 1.013, p = 0.674). Subgroup analysis suggested that biopsy may benefit patients with advanced stage IV-B by enabling more aggressive treatment strategies. Conclusions: Liver biopsy rates fluctuated over time, with the majority of HCC diagnoses made through imaging. Although biopsy does not significantly affect OS or TFS, it may provide advantages in advanced cases, such as stage IV-B, by guiding more aggressive treatment strategies. Full article

Objectives: this study aimed to compare the admission volume and characteristics of patients with traumatic orthopaedic injuries before, during, between, and after the COVID-19 lockdowns in metropolitan Victoria, Australia. Methods: A multi-centre, registry-based cohort study with an interrupted time series analysis was conducted using data from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) for patients with a date of injury from January 2017 to June 2022. Weekly admission volume, injury event characteristics, and in-hospital outcomes were analysed before, during, between, and after the two periods of COVID-19 lockdowns in metropolitan Melbourne (i.e., five periods). Results: During the first week of lockdown in Victoria (L1), the number of weekly orthopaedic trauma admissions declined by 24% relative to the preceding week, IRR 0.76 (95%CI 0.67, 0.87). However, the volume of admissions during the subsequent lockdown (L2) approximated pre-COVID levels. An immediate increase in orthopaedic trauma admissions occurred during the intermission (time between lockdowns) and post-COVID periods by 33% and 20%, respectively, compared to the preceding week. During periods of lockdown, patients were older (61 versus 58 years old), and a higher proportion were injured at home (38% versus 28%); fewer due to motor vehicle collisions (8% versus 11%). The pattern of injury by intent, body region injured, injury severity, and in-hospital mortality were unchanged. Conclusions: the impact of COVID-19 lockdowns on the volume and characteristics of hospitalised orthopaedic trauma was not uniform across consecutive lockdowns, but favoured injuries that occurred at home. Full article

Background: Real-world data on currently used biologic agents in patients with severe asthma are lacking. Methods: In this retrospective study, we recorded between 16 May 2020 and 31 December 2024 consecutive patients who presented to our asthma outpatient clinic received a diagnosis of uncontrolled severe asthma and were treated with biologic agents. Outcomes included a comparison of disease phenotypic characteristics, as well as asthma control, lung function, longitudinal use of corticosteroids, and hospitalizations due to exacerbations at baseline and post-biologic treatment at 6-month follow-up. Results: We identified 80 patients with uncontrolled severe asthma treated with biologic agents. The median age (95% CI) at the time of diagnosis was 67.0 (61.0 to 70.0) years. Most patients were female (65.0%, n = 52) and never smokers (51.3%, n = 41). The median value of ACT (95% CI) was 15 (15 to 16) at the time of diagnosis. The mean FEV₁% predicted ±SD at the baseline was 68.9 ± 22.0. The median value of blood eosinophils (95% CI) was 365 (252 to 448) K/μL in the overall population. One-third (36.3%) of patients were hospitalized due to severe asthma exacerbation in the previous year. Longitudinal use of oral corticosteroids was recorded in 11.3% of included patients. Three patients (3.8%) were treated with omalizumab, 23 patients (28.8%) with mepolizumab, 33 patients (41.2%) with benralizumab and 21 patients (26.2%) with tezepelumab. The median value of ACT (95% CI) post-biologic treatment at 6-month follow-up was 20 (20 to 21), p < 0.0001. The mean FEV₁% predicted ±SD at 6-month follow-up was 77.6 ± 25.2, p = 0.12. The median value of blood eosinophils (95% CI) 6 months after initiation of biologic treatment was 100 (40 to 121) K/μL, p < 0.0001. Elimination of hospitalizations due to asthma flares was recorded in 97.5% of patients (p < 0.0001). With regard to the longitudinal use of oral corticosteroids, we noticed that 96.2% of patients achieved discontinuation. No treatment-related adverse events were noticed. Conclusions: The administration of current biologic agents in patients with severe asthma seems to be both effective and safe, sparing the toxicity of oral corticosteroids. Full article

Background: While various techniques for the surgical correction of urethral strictures exist, data on their trends and perioperative outcomes are limited. Methods: Data from the German Nationwide Inpatient Data (GRAND) registry (2005–2023) were used to estimate the trends, baseline characteristics, and perioperative outcomes of the surgical techniques for urethral stricture correction. Results: A total of 500,937 patients underwent surgery. Internal urethrotomy was the most frequently performed procedure (n = 413,095, 82%), followed by urethral dilatation (n = 39,619, 8%), meatoplasty (n = 30,774, 6%), urethroplasty with buccal mucosa (n = 12,351, 2%), urethral excision with primary anastomosis (n = 3428, 0.7%), urethroplasty with preputial skin (n = 1585, 0.3%), and drug-coated balloon dilatation (n = 85, <0.1%). In recent years, internal urethrotomy declined; urethroplasty was relatively stable, and drug-coated balloon dilatation emerged as a promising treatment modality. Internal urethrotomy and urethral dilatation were predominantly performed in older patients (median age of 71 years), while urethroplasty was performed in younger (56 years). Preputial skin urethroplasty had a shorter hospital stay compared to buccal mucosa (−0.4 days, p = 0.02), with no significant differences in transfusion or sepsis rates. Conclusions: Internal urethrotomy remains the most frequently used technique despite declining utilization. Preputial skin urethroplasty presents similar perioperative outcomes compared to buccal mucosa urethroplasty. Full article