Background: s/Aims: Pancreaticoduodenectomy (PD) is the standard treatment for periampullary tumors, but it is technically challenging. Evidence directly comparing open, laparoscopic, robotic, and hybrid approaches is limited. This study conducts a network meta-analysis (NMA) to compare the perioperative and oncologic outcomes of open PD (OPD), laparoscopic PD (LPD), robotic PD (RPD), and hybrid PD. Methods: We searched PubMed, EMBASE, and the Cochrane Library for studies published between January 1994 and August 2024.We included randomized controlled trials and comparative observational studies that evaluated at least two PD approaches. Perioperative outcomes were the primary endpoints, while oncologic safety served as a secondary endpoint. A random-effects NMA was performed, establishing treatment hierarchies through ranking probabilities (PROSPERO ID: CRD420250365864). Results: A total of 78 studies were included (5 randomized and 73 retrospective). RPD was associated with lower blood loss compared to OPD (mean difference [MD], –163.85 mL) and LPD (MD, –84.14 mL). Hospital stays were also shorter for RPD compared to OPD (MD, –2.50 days) and LPD (MD, –1.88 days). In contrast, OPD was the most time-efficient approach compared to LPD (MD, –77.61 minutes) and RPD (MD, –73.30 minutes). Mortality rates, severe complications, clinically relevant postoperative pancreatic fistula rates, and reoperation rates were comparable across all surgical approaches. In terms of oncologic safety, lymph node yield and R0 resection rates were similar for all modalities. Conclusions While OPD is the most time-efficient approach, RPD provides significant advantages in reducing intraoperative blood loss and shortening hospital stays compared to both LPD and OPD.

Mitochondrial bioenergetics plays a fundamental role in neuronal development and function. Prenatal exposure to corticosterone in rats (Corti.Pup) has previously been shown to cause delayed neurodevelopment and synaptic plasticity deficits, showing attention deficit hyperactivity disorder (ADHD) - like behaviors. However, the underlying mitochondrial metabolic adaptations remain unclear. This study investigated mitochondrial function and metabolic remodeling in prefrontal cortex neurons of Corti.Pups, focusing on oxidative phosphorylation, calcium handling, and redox balance. We assessed neuronal viability, reactive oxygen species (ROS) production, and oxygen consumption rate (OCR) through experiments conducted in both neuron-glia co-culture and neuron-only conditions. Furthermore, we evaluated electron transport chain (ETC) activity, mitochondrial membrane potential (MMP), and mitochondrial Ca2+ uptake in purified isolated mitochondria. In results, Corti.Pup neurons exhibited increased vulnerability to glutamate-induced excitotoxicity in the absence of glial support. Despite reduced ROS production, these neurons showed elevated mitochondrial OCR and proton leak, coupled with decreased non-mitochondrial OCR and ETC complex activity. Surprisingly, MMP remained elevated despite ETC dysfunction, and mitochondrial Ca2+ uptake was suppressed. These features indicate mitochondrial metabolic reprogramming, prioritizing MMP maintenance over ATP synthesis. The observed mitochondrial inefficiency and compensatory adaptations may impair energy production, contributing to delayed neuronal development in Corti.Pups. These findings suggest that mitochondrial dysfunction and metabolic remodeling play central roles in the pathogenesis of neurodevelopmental disorders such as ADHD.

Objective: Primary frozen shoulder causes significant pain and progressively restricts shoulder movements. Diagnosis is made clinically based on patient history and physical examination. Management is mainly non-invasive owing to its self-limiting clinical course. However, clinical practice guidelines for frozen shoulder have not yet been developed in Korea. The developed guidelines aim to provide evidence-based recommendations for the diagnosis and treatment of frozen shoulder. Methods: A guideline development committee reviewed the literature from four databases (PubMed, Embase, Cochrane Library, and KMbase). Using the Population, Intervention, Comparator, and Outcome (PICO) framework, the committee formulated two backgrounds and 16 key questions to address common clinical concerns. Recommendations were made using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Results: Diabetes, thyroid disease, and dyslipidemia significantly increase the risk of developing a frozen shoulder. Although frozen shoulder is often self-limiting, some patients may experience long-term functional disabilities. Ultrasound and magnetic resonance imaging should be used as adjunctive tools alongside clinical diagnosis, and rather than as independent diagnostic methods. Noninvasive approaches, such as medications, physical modalities, exercises, electrical stimulation, and manual therapy, may reduce pain and improve shoulder function. Other noninvasive interventions have limited evidence, and their application should be based on clinical judgment. Intra-articular steroid injections are recommended for treatment, and physiotherapy or hydrodilation with steroid injections can also be beneficial. Conclusion These guidelines provide evidence-based recommendations for diagnosing and treating primary frozen shoulder.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. Methods: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. Results: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. Conclusions We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Background: Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas. Methods: This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis. Results: In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively). Conclusions There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue diseaseILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone.Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

Background: The association between endovascular treatment (EVT) case volume per hospital and clinical outcomes has been reported, but the exact volume threshold has not been determined. This study aimed to examine the case volume threshold in this context. Methods: National audit data on the quality of acute stroke care in patients admitted via emergency department, within 7 days of onset, in hospitals that treated ≥ 10 stroke cases during the audit period were analyzed. Ischemic stroke cases treated with EVT during the last three audits (2013, 2014, and 2016) were selected for the analysis. Annual EVT case volume per hospital was estimated and analyzed as a continuous and a categorical variable (in quartiles). The primary outcome measure was 1-year mortality as a surrogate of 3-month functional outcome. As post-hoc sensitivity analysis, replication of the study results was examined using the 2018 audit data. Results: We analyzed 1,746 ischemic stroke cases treated with EVT in 120 acute care hospitals. The median annual EVT case volume was 12.0 cases per hospital, and mortality rates at 1 month, 3 months, and 1 year were 12.7%, 16.6%, and 23.3%, respectively. Q3 and Q4 had 33% lower odds of 1-year mortality than Q1. Adjustments were made for predetermined confounders. Annual EVT case volume cut-off value for 1-year mortality was 15 cases per year (P < 0.02). The same cut-off value was replicated in the sensitivity analysis. Conclusion Annual EVT case volume was associated with 1-year mortality. The volume threshold per hospital was 15 cases per year.

Objective: Muscle quantity and quality can be measured with an automated system on CT. However, the effects of contrast phases on the muscle measurements have not been established, which we aimed to investigate in this study. Materials and Methods: Muscle quantity was measured according to the skeletal muscle area (SMA) measured by a convolutional neural network-based automated system at the L3 level in 89 subjects undergoing multiphasic abdominal CT comprising unenhanced phase, arterial phase, portal venous phase (PVP), or delayed phase imaging. Muscle quality was analyzed using the mean muscle density and the muscle quality map, which comprises normal and low-attenuation muscle areas (NAMA and LAMA, respectively) based on the muscle attenuation threshold. The SMA, mean muscle density, NAMA, and LAMA were compared between PVP and other phases using paired t tests. Bland-Altman analysis was used to evaluate the inter-phase variability between PVP and other phases. Based on the cutoffs for low muscle quantity and quality, the counts of individuals who scored lower than the cutoff values were compared between PVP and other phases. Results: All indices showed significant differences between PVP and other phases (p < 0.001 for all). The SMA, mean muscle density, and NAMA increased during the later phases, whereas LAMA decreased during the later phases. Bland-Altman analysis showed that the mean differences between PVP and other phases ranged -2.1 to 0.3 cm2 for SMA, -12.0 to 2.6 cm2 for NAMA, and -2.2 to 9.9 cm2 for LAMA.The number of patients who were categorized as low muscle quantity did not significant differ between PVP and other phases (p ≥ 0.5), whereas the number of patients with low muscle quality significantly differed (p ≤ 0.002). Conclusion SMA was less affected by the contrast phases. However, the muscle quality measurements changed with the contrast phases to greater extents and would require a standardization of the contrast phase for reliable measurement.

Background: and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. Methods: This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). Results: Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. Conclusions Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.