Total Hip Arthroplasty with Extra-small Femoral Stems in Extremely Hypoplastic Femurs: A Case-Series Study.

Background: Total hip arthroplasty (THA) in patients with hypoplastic femurs presents a significant challenge to orthopedic surgeons due to the limited space available for implant placement. Therefore, the extra-small femoral stems have been proposed as a solution to this problem, but there are limited data on the outcomes. We aimed to evaluate clinical and radiological outcomes of THA in patients with extremely hypoplastic femurs using the Bencox CM stem (Corentec), an extra-small femoral stem. Methods: We included 6 hips from 4 patients. The mean age of the patients was 41.2 years (range, 19.6-60.4 years). The mean height was 135.1 cm (range, 113.6-150.0 cm) with a mean body mass index of 25.7 kg/m2 (range, 21.3-31.1 kg/m2). The diagnoses for THA were sequelae of septic arthritis in childhood, pseudoachondroplasia, spondyloepiphyseal dysplasia, and juvenile rheumatoid arthritis. Preoperative computed tomography scans were conducted to assess the extent of proximal femoral hypoplasia. The clinical outcomes were assessed using the modified Harris Hip Score, while the radiological outcomes were evaluated using radiographs. The mean follow-up was 2.3 years (range, 1.0-5.9 years). Results: The average modified Harris Hip Score improved to 88.8 at the final follow-up. Intraoperative femoral fractures occurred in 2 cases (33.3%). During the follow-up, 1 stem underwent varus tilting from postoperative 6 weeks to 6 months without subsidence. Otherwise, all stems showed good osteointegration at the latest follow-up. No hip dislocations, periprosthetic joint infection, or loosening of the prosthesis occurred. Conclusions: The use of extra-small femoral stems in THA for extremely hypoplastic femurs can provide reasonable clinical and radiological outcomes with minimal complications. We suggest that this femoral stem could be a viable option for patients with extremely hypoplastic femurs.

Severe acquired hemophilia A associated with COVID-19 vaccination: A case report and literature review.

RATIONALE: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an antibody that inhibits coagulation factor VIII activity. More than half of patients with AHA cannot identify underlying disorders. The remaining patients are associated with malignancies, autoimmune diseases, skin diseases, infections, and medications. Here, we present a case of 56-year-old Korean man with underlying hypertension, dyslipidemia, and diabetes mellitus who developed AHA following the second dose of BNT162b2 COVID-19 vaccination. PATIENT CONCERNS: He presented with a large 20 × 30 cm-sized hematoma along the psoas muscle and intracranial hemorrhage, necessitating intensive care with mechanical ventilation and continuous renal replacement therapy. Laboratory testing demonstrated that activated partial thromboplastin time and prothrombin times were 74.7 seconds (normal range 29-43 seconds) and 17.2 seconds (normal range 12.5-14.7 seconds), respectively. DIAGNOSES: Laboratory tests confirmed AHA with undetectable factor VIII activity (<1.5%) and a positive factor VIII antibody with a titer of 8.49 Bethesda units/mL. INTERVENTIONS: Recombinant factor VIIa (NovoSeven®) was administered every 2 hours to control the bleeding, alongside immunosuppression with methylprednisolone 1 mg/kg daily and cyclophosphamide 2 mg/kg daily to eliminate the autoantibody. OUTCOMES: Despite the treatments, the patient developed sepsis and succumbed 14 weeks after admission. LESSONS: This rare case underscores the importance of monitoring for AHA following COVID-19 vaccination. Although the benefits outweigh the risks of vaccination, AHA should be considered in the differential diagnosis of unusual bleeding following the vaccinations. Early diagnosis and management before severe bleeding are critical for successfully controlling life-threatening bleeding.

A novel treatment strategy targeting cellular pathways with natural products to alleviate sarcopenia.

Sarcopenia is a condition marked by a significant reduction in muscle mass and strength, primarily due to the aging process, which critically impacts muscle protein dynamics, metabolic functions, and overall physical functionality. This condition leads to increased body fat and reduced daily activity, contributing to severe health issues and a lower quality of life among the elderly. Recognized in the ICD-10-CM only in 2016, sarcopenia lacks definitive treatment options despite its growing prevalence and substantial social and economic implications. Given the aging global population, addressing sarcopenia has become increasingly relevant and necessary. The primary causes include aging, cachexia, diabetes, and nutritional deficiencies, leading to imbalances in protein synthesis and degradation, mitochondrial dysfunction, and hormonal changes. Exercise remains the most effective intervention, but it is often impractical for individuals with limited mobility, and pharmacological options such as anabolic steroids and myostatin inhibitors are not FDA-approved and are still under investigation. This review is crucial as it examines the potential of natural products as a novel treatment strategy for sarcopenia, targeting multiple mechanisms involved in its pathogenesis. By exploring natural products' multi-targeted effects, this study aims to provide innovative and practical solutions for sarcopenia management. Therefore, this review indicates significant improvements in muscle mass and function with the use of specific natural compounds, suggesting promising alternatives for those unable to engage in regular physical activity.

Comparison of the treatment outcomes of different neoadjuvant chemoradiotherapy regimens for resectable locally advanced esophageal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by radical esophagectomy is the standard treatment for locally advanced esophageal squamous cell cancer (LA-ESCC). However, various nCRT regimens have been used and their comparative efficacy and safety remain unclear. METHODS: Patients with histologically confirmed LA-ESCC who underwent nCRT followed by radical esophagectomy between January 2016 and February 2022 were enrolled in our study. Three different nCRT regimens were retrospectively compared: Conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP) (Conv-FP), hypofractionated RT + FP (Hypo-FP), and regimens from the CROSS trial (CROSS). The overall survival (OS), pathological complete response (pCR) rates, toxicities, and treatment compliance were analyzed. RESULTS: Among the 600 patients, 225 received Conv-FP, 255 received Hypo-FP, and 120 received the CROSS regimen. OS at 1 year were 78.7%, 83.9%, and 88.1% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (p < 0.001). The pCR rates were 30.6%, 33.9%, and 35.0%, respectively (p = 0.653). The overall incidence of grade 3 toxicities was 10.2%. Hematologic and non-hematologic toxicities of grade ≥ 3 were observed in 8.4% and 11.4%, 0% and 7.6%, 5.5% and 0.8% in Conv-FP, Hypo-FP, and CROSS, respectively (p = 0.002 and 0.030). Weight loss > 5% was observed in 44.0%, 51.4%, and 32.5%, respectively (p < 0.001). In the multivariate analysis, clinical T-stage (p = 0.004), N-stage (p = 0.012), the use of FP chemotherapy regimen (p = 0.013), surgical resection (p < 0.001), hematologic toxicity (p = 0.001), and weight loss (p = 0.004) were significantly associated with poor OS. CONCLUSION: The choice of nCRT regimen did not significantly affect the pCR rates in patients with LA-ESCC. However, the CROSS regimen demonstrated better OS and lower toxicity, suggesting it may be the optimal treatment option among the groups. SYNOPSIS: This study compared three different neoadjuvant chemoradiotherapy (nCRT) regimens for locally advanced esophageal squamous cell cancer (LA-ESCC): Conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP), hypofractionated RT + FP, and regimens from the CROSS trial. The overall survival (OS), pathological complete response (pCR) rates, toxicities, and treatment compliance were analyzed. Results showed that the choice of nCRT regimen did not significantly affect pCR rates, but the CROSS regimen showed better OS and lower toxicity, suggesting it may be the optimal treatment option. DATA AVAILABILITY: Data availability is limited due to institutional data protection law and confidentiality of patient data.

Lymph node metrics following neoadjuvant therapy to refine patient selection for adjuvant chemotherapy in resected pancreatic cancer: A multi-institutional analysis.

BACKGROUND: In patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high-risk features on histopathologic examination. We evaluated the interaction between post-NAT lymph node metrics and AC receipt on survival. METHODS: Patients who received NAT followed by pancreatectomy (2010-2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS. RESULTS: Of 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien-Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post-NAT LNP rates were not different, and median LNR was 0.1, in AC and non-AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non-AC (24 vs. 20 months, respectively; p = 0.04). CONCLUSIONS: LNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC.

Longitudinal multiomic profiling and corticosteroid modulation of the immediate innate immune response to an adenovirus-vector vaccine.

Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.

Factors Associated with Postoperative Recurrence in Stage I to IIIA Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data.

Purpose: Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion: Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Eight-Year Prevalence Trends of Lumbar Spondylolysis and Isthmic Spondylolisthesis in Adolescent Males: A Population-Based Study from a Nationwide Military Draft Medical Examination Database in South Korea.

OBJECTIVE: To assess the national and regional trend in the prevalence of lumbar spondylolysis and isthmic spondylolisthesis for adolescent males in South Korea from 2015 to 2022. METHODS: A total of 2,666,277 Korean adolescent males were routinely examined at regional Military Manpower Administration offices. The data gathered from Military Manpower Administration were retrospectively collected to measure the prevalence and 95% confidence interval of lumbar spondylolysis and isthmic spondylolisthesis according to the year and region in South Korea. The Spearman correlation analysis was performed to assess the correlation between lumbar spondylolysis, isthmic spondylolisthesis, and several factors including height, weight, current smoking rate, and occasional and high-risk alcohol consumption. RESULTS: The prevalence of spondylolysis per 10,000 individuals showed a gradual increasing trend from 2015 to 2022 On the contrary, the prevalence of isthmic spondylolisthesis per 10,000 individuals decreased over a consecutive 8-year period. There were no statistical differences in the prevalence of spondylolysis and isthmic spondylolisthesis between Greater Seoul and the countryside. The prevalence of isthmic spondylolisthesis was significantly correlated with occasional (r=0.81, P=0.015) and high-risk alcohol consumption (r=0.86, P=0.007). CONCLUSIONS: The prevalence of lumbar spondylolysis among adolescent men has increased, whereas isthmic spondylolisthesis has shown a decline over a consecutive 8-year period. The trends in prevalence for both lumbar spondylosis and isthmic spondylolisthesis were similar across the regions in South Korea. Notably, there was a significant correlation between the prevalence of isthmic spondylolisthesis and the rate of alcohol consumption in adolescent men.

The prognostic role of aspartate transaminase to platelet ratio index on outcomes after nonemergent major hepatectomy.

INTRODUCTION: Noninvasive screening methods to identify patients preoperatively with abnormal liver texture remain limited. Aspartate transaminase to platelet ratio index has been validated to predict fibrosis in patients with hepatitis C; however, its use as a predictor of postoperative outcomes in patients without viral hepatitis remains unknown. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program dataset to identify patients who underwent a major hepatectomy between 2014 and 2021. We excluded patients who underwent emergent operations, patients with viral hepatitis, and patients with ascites. Aspartate transaminase to platelet ratio index was calculated using the following equation: (aspartate transaminase/40)/(platelet count) × 100. An aspartate transaminase to platelet ratio index ≥0.7 was used to identify patients with significant fibrosis. Univariable analysis was performed to identify factors associated with aspartate transaminase to platelet ratio index ≥0.7, perioperative transfusion, serious morbidity, overall morbidity, and 30-day mortality. Multivariable logistic regression analysis was performed to identify adjusted predictors of these outcomes. RESULTS: Of the 8,933 patients who met inclusion criteria, 1,170 (13.1%) patients had an aspartate transaminase to platelet ratio index ≥0.7. A perioperative blood transfusion was administered to 2,497 (28.0%). The number of patients who experienced overall morbidity, serious morbidity, and mortality were 3,195 (35.8%), 2,665 (29.8%), and 238 (2.7%), respectively. Aspartate transaminase to platelet ratio index ≥0.7 was an independent predictor of transfusion (odds ratio: 1.51 [1.32-1.72], P < .001), overall morbidity (1.16 [1.01-1.33], P = .032), and mortality (1.56 [1.12-2.13], P = .006). Transfusion was an independent predictor of overall morbidity (2.50 [2.26-2.76], P < .001), serious morbidity (2.51 [2.26-2.79], P < .001), and mortality (3.28 [2.49-4.33], P < .001). CONCLUSION: An aspartate transaminase to platelet ratio index ≥0.7 is associated with perioperative transfusion, overall morbidity, and 30-day mortality. The aspartate transaminase to platelet ratio index may serve as a noninvasive tool to risk stratify patients before elective major hepatectomy.

Comparison of the Oncologic Outcomes for Patients with Middle to Lower Esophageal Squamous Cell Carcinoma Undergoing Surgical Treatment Using the Ivor-Lewis or McKeown Operation.

BACKGROUND: The upper mediastinum is the most common metastatic site of esophageal squamous cell carcinoma (ESCC), and complete dissection of this region is important for oncologic reasons. This study aimed to compare the oncologic outcomes and completeness of upper mediastinal dissection for ESCC patients undergoing the Ivor-Lewis (IL) or McKeown (MK) operations. METHODS: Between 2013 and 2018, 680 patients (IL, 433; MK, 247) underwent upfront esophagectomy with two-field lymph node (LN) dissection for mid-to-lower ESCCs. Propensity score-matching (1:1 ratio) was performed to minimize the effects of confounding factors. RESULTS: The mean age was 64.5 ± 8.8 years, and 635 (93.4%) of the patients were male. The median follow-up period was 71.66 months (interquartile range [IQR], 59.60-91.04 months). The IL group had a higher mean age, lower body mass index, higher proportion of advanced T and N, and higher adjuvant therapy rates, but these differences were well-balanced after propensity score-matching. The mean number of dissected LNs at the mediastinum and at the right recurrent laryngeal nerve (RLN) were similar between the two groups after matching, whereas the IL group exhibited a slightly greater number of dissected LNs at the left RLN. Among the matched patients, the IL and MK groups exhibited similar 5-year overall survival (OS: 75.1% vs 78.0%; p = 0.368). The multivariate model showed no differences in OS, disease-free survival, or recurrence-free survival for locoregional, upper mediastinum, or neck between the two groups. CONCLUSIONS: This study suggests that both the IL and MK operations are oncologically feasible for patients with mid-to-lower ESCC.

18F-Fluorodeoxyglucose Positron Emission Tomography-Based Risk Score Model for Prediction of Five-Year Survival Outcome after Curative Resection of Non-Small-Cell Lung Cancer.

The aim of our retrospective study is to develop and assess an imaging-based model utilizing 18F-FDG PET parameters for predicting the five-year survival in non-small-cell lung cancer (NSCLC) patients after curative surgery. A total of 361 NSCLC patients who underwent curative surgery were assigned to the training set (n = 253) and the test set (n = 108). The LASSO regression model was used to construct a PET-based risk score for predicting five-year survival. A hybrid model that combined the PET-based risk score and clinical variables was developed using multivariate logistic regression analysis. The predictive performance was determined by the area under the curve (AUC). The individual features with the best predictive performances were co-occurrence_contrast (AUC = 0.675) and SUL peak (AUC = 0.671). The PET-based risk score was identified as an independent predictor after adjusting for clinical variables (OR 5.231, 95% CI 1.987-6.932; p = 0.009). The hybrid model, which integrated clinical variables, significantly outperformed the PET-based risk score alone in predictive accuracy (AUC = 0.771 vs. 0.696, p = 0.022), a finding that was consistent in the test set. The PET-based risk score, especially when integrated with clinical variables, demonstrates good predictive ability for five-year survival in NSCLC patients following curative surgery.

Impact of multidrug resistance on outcomes in hematologic cancer patients with bacterial bloodstream infections.

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003-2007) to 39.7% (2018-2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum ß-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes.

Mitral valve repair with leaflet resection versus preservation for degenerative posterior leaflet prolapse.

OBJECTIVES: The optimal technique for repairing posterior mitral valve leaflet prolapse remains undetermined. We aimed to compare leaflet resection and neochordae implantation in patients undergoing mitral valve repair for posterior leaflet prolapse, focusing on transmitral pressure gradient and recurrence of mitral regurgitation. METHODS: We enrolled patients undergoing mitral valve repair using either leaflet resection or neochordae implantation for single-segment prolapse of posterior mitral valve leaflet between 2000 and 2021 at our institution. Longitudinal outcomes were evaluated after adjustments with inverse-probability-of-treatment weighting. Repeat echocardiographic measurements (n = 3473, 5.4/patient) of transmitral pressure gradient and significant (moderate or severe) mitral regurgitation recurrence were estimated using nonlinear mixed-effect models. Subgroup analyses were conducted based on the size and type of prosthesis. RESULTS: Among 639 patients, leaflet resection was used in 479 (75.0%) and neochordae implantation was used in 160 (25.0%). In the inverse-probability-of-treatment weighting adjusted cohort, the risk of death (P = .623) and mitral valve reoperation (P = .340) did not significantly differ between the 2 groups during a median follow-up of 97.3 months. Echocardiographic data showed comparable mean (at 5 years, 3.8 vs 4.0 mm Hg; P = .442) and peak (9.6 vs 10.4 mm Hg; P = .131) pressure gradients between groups, which persisted in most subgroup analyses. However, neochordae implantation was associated with a higher probability of significant mitral regurgitation recurrence compared with leaflet resection (at 5 years, 16.1% vs 7.0%; P < .001). CONCLUSIONS: Leaflet resection yielded similar clinical outcomes and transmitral pressure gradients compared with neochordae implantation after mitral valve repair, with a lower mitral regurgitation recurrence rate. These findings underscore the need to reassess the efficacy of neochordae implantation relative to leaflet resection.

Association between metabolic dysfunction-associated steatotic liver disease and myosteatosis measured by computed tomography.

BACKGROUND: In 2023, the concept of metabolic dysfunction-associated steatotic liver disease (MASLD) was introduced as an alternative to non-alcoholic fatty liver disease (NAFLD). We aimed to assess the quantity and quality of skeletal muscle using each of these diagnostic classifications. METHODS: This cross-sectional study included 18 154 participants (11 551 [63.6%] men and 6603 [36.4%] women, mean age 53.0 ± 8.8). The participants were classified into four categories: neither steatotic liver disease (SLD), NAFLD only, MASLD only or both SLDs. An appendicular skeletal muscle mass adjusted for body mass index of <0.789 for men and <0.512 for women was defined as sarcopenia. The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area and intermuscular/intramuscular adipose tissue. Myosteatosis was defined by a T-score < -1.0 of the NAMA/TAMA index, which was calculated by dividing the NAMA by the TAMA and multiplying by 100. RESULTS: Using subjects with neither SLD as a reference, the multivariable-adjusted odds ratios (ORs) for sarcopenia were significantly increased in those with MASLD, with adjusted ORs (95% confidence interval [CI]) of 2.62 (1.94-3.54) in the MASLD-only group and 2.33 (1.92-2.82) in the both SLDs group, while the association was insignificant in those with NAFLD only (adjusted OR [95% CI]: 2.16 [0.67-6.94]). The OR for myosteatosis was also elevated in the MASLD groups, with an OR (95% CI) of 1.75 (1.52-2.02) in subjects with MASLD only and 1.70 (1.57-1.84) in those with both SLDs, while it was slightly decreased in subjects with NAFLD only (0.52 [0.29-0.95]). CONCLUSIONS: Employing the MASLD concept rather than that of the NAFLD proved to be more effective in distinguishing individuals with reduced muscle mass and compromised muscle quality.

Recombinant Human IL-32θ Induces Polarization Into M1-like Macrophage in Human Monocytic Cells.

The tumor microenvironment (TME) is formed by several immune cells. Notably, tumor-associated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32θ was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) was generated using an Escherichia coli expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32θ. The mRNA level of M1 macrophage markers (IL-1ß, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFß, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.

Clinical Implications of Polypharmacy for Patients with New-Onset Atrial Fibrillation Based on Real-World Data: Observations from the Korea National Health Insurance Service Data.

Background: Polypharmacy is commonly observed in atrial fibrillation (AF) and is associated with poorer clinical outcomes. Our study aimed to elucidate the polypharmacy prevalence, its associated risk factors, and its relationship with adverse clinical outcomes using a 'real-world' database. Methods: This study included 451,368 subjects without prior history of AF (median age, 54 [interquartile range, 48.0-63.0] years; 207,748 [46.0%] female) from the Korea National Health Insurance Service-Health Screening (NHIS-HealS) database between 2002 and 2013. All concomitant medications prescribed were collected, and the intake of five or more concomitant drugs was defined as polypharmacy. During the follow-up, all-cause death, major bleeding events, transient ischemic attack (TIA) or ischemic stroke, and admission due to worsened heart failure were recorded. Results: Based on up to 7.7 (6.8-8.3) years of follow-up and 768,306 person-years, there were 12,241 cases of new-onset AF identified. Among patients with new-onset AF (40.0% females, median age 63.0 [54.0-70.0] years), the polypharmacy prevalence was 30.9% (3784). For newly diagnosed AF, factors, such as advanced age (with each increase of 10 years, odds ratios (OR) 1.32, 95% confidence interval (CI) 1.26-1.40), hypertension (OR 4.00, 95% CI 3.62-4.43), diabetes mellitus (OR 3.25, 95% CI 2.86-3.70), chronic obstructive pulmonary disease (COPD) (OR 3.00, 95% CI 2.51-3.57), TIA/ischemic stroke (OR 2.36, 95% CI 2.03-2.73), dementia history (OR 2.30, 95% CI 1.06-4.98), end-stage renal disease (ESRD) or chronic kidney disease (CKD) (OR 1.97, 95% CI 1.38-2.82), and heart failure (OR 1.95, 95% CI 1.69-2.26), were found to be independently correlated with the incidence of polypharmacy. Polypharmacy significantly increased the incidence and risk of major bleeding (adjusted hazard ratio (aHR) 1.26, 95% CI 1.12-1.41). The study observed a statistically significant increase in the incidence of all-cause mortality, however, the risk for all-cause mortality elevated but did not show significance (aHR 1.11, 95% CI 0.99-1.24). The risk of stroke and admission for heart failure did not change with polypharmacy. Conclusions: In our investigation using data from a nationwide database, polypharmacy was widespread in new-onset AF population and was related to major bleeding events. However, polypharmacy does not serve as an independent risk factor for adverse outcomes, with exception of major bleeding event. For AF patients, ensuring tailored medication for comorbidities as well as reducing polypharmacy are essential considerations.

Salvage Radiotherapy for Loco-Regional Recurrence of Esophageal Cancer Following Surgery.

Purpose: There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer. Materials and Methods: We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT). Results: The patients' median age was 65 (41-86). The median disease-free interval (DFI) was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023). Conclusion: Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

Clinical Utility of Tumor-Naïve Presurgical Circulating Tumor DNA Detection in Early-Stage NSCLC.

OBJECTIVES: The use of tumor-informed circulating tumor DNA (ctDNA) testing in patients with early-stage disease before surgery is limited, mainly owing to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected NSCLC. METHOD: We analyzed presurgical plasma samples from 895 patients with EGFR and anaplastic lymphoma kinase-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histologic diagnosis, histologic subtypes, and clinical-to-pathologic TNM upstaging. RESULTS: Presurgical ctDNA detection was observed in 55 of 414 patients (13%) with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (2-year recurrence-free survival 69% versus 91%; log-rank p < 0.001), approaching that of clinical stage II LUAD. Presurgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict presurgical ctDNA detection. Moreover, presurgical ctDNA detection was predictive of the postsurgical discovery of International Association for the Study of Lung Cancer grade 3 tumors (p < 0.001) and pathologic TNM upstaging (p < 0.001). Notably, presurgical ctDNA detection strongly correlated with higher programmed death-ligand 1 expression in tumors (positive rates 28% versus 55%, p < 0.001), identifying a subgroup likely to benefit from anti-programmed death-ligand 1 therapies. CONCLUSION: These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need for tumor tissue profiling. Furthermore, it is clinically useful in identifying patients at high risk who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

Trends in Hospital Stay, Complication Rate, and Mortality in Hip Fracture Patients: A Two-Decade Comparison at a National Tertiary Referral Center.

Background: Since the turn of the century, the age-adjusted incidence of proximal femoral fractures has caused a plateau or fall. However, it was anticipated that the number of patients with proximal femoral fractures would rise as life expectancy rose and the population over 80 years old expanded. The aim of this study was to compare the length of hospital stay, complication rate, and mortality in patients with proximal femoral fractures between two different time periods: 20 years ago and the present. Methods: We conducted a retrospective review of medical records of patients aged 65 years and above who underwent surgery for proximal femoral fractures between January 2000 and December 2001 and between January 2020 and December 2021. We collected information on age, gender, fracture type, length of hospital stay, and complication rate. Dates of death were obtained from the Ministry of the Interior and Safety. Results: We included 136 patients who were operated on between 2000 and 2001 and 134 patients between 2020 and 2021. The average age increased significantly from 71.6 years to 79.0 years (p < 0.001). The length of hospital stay decreased dramatically from 15.1 days to 6.0 days (p < 0.001). There was no statistically significant difference in delirium, urinary tract infection, or pneumonia. No difference was found in 30-day or 1-year mortality between the two groups. Conclusions: The complication rate and mortality between the two time periods appeared comparable, although the length of hospital stay decreased substantially. Therefore, we recommend considering expedited discharge from the acute care hospital for elderly hip fracture patients while implementing an individualized approach for better outcomes.