Therapeutic efficacy of platelet-rich plasma in the management of rib fractures.

BACKGROUND: This study aimed to investigate the therapeutic efficacy of platelet-rich plasma (PRP) therapy in patients with rib fractures. METHODS: This study retrospectively collected data from patients with acute rib fractures at Ming-Sheng General Hospital from 2020 to 2022 and excluded those who underwent surgical intervention or with severe extrathoracic injuries. PRP was extracted using the patient's blood and injected via ultrasound guidance near the fracture site. Patients self-assessed pain levels and medication usage at 0, 1, 2, 4, and 8 weeks. Pulmonary function tests were conducted at 4 weeks. RESULTS: This study included 255 patients, with 160 and 95 patients in the conservative (only pain medications administered) and PRP groups (PRP and analgesics administered), respectively. The PRP group reported lower pain levels than the conservative group at 2 and 4 weeks. No substantial differences in medication usage were observed between the groups. The PRP group demonstrated considerably lower pain levels and medication usage than the conservative group in severe rib fractures (≥3 ribs) and improved lung function at 4 weeks. After propensity score matching, the PRP group still had a better treatment outcome in pain control and lung function recovery. CONCLUSION: PRP demonstrated considerable therapeutic efficacy in patients with severe rib fractures, resulting in reduced pain, decreased medication usage, and improved lung function but with no substantial benefits in patients with mild rib fractures.

Increased risk of chronic fatigue syndrome following pneumonia: A population-based Cohort study.

BACKGROUND: Chronic fatigue syndrome (CFS) has been linked to several conditions, including infections, immune system changes, or emotional stress. Our study aimed to assess the risk of CFS after a pneumonia diagnosis using data from National Health Insurance Research Database of Taiwan. METHODS: In this nested case-control study, we identified 2,000,000 adult patients from a nationwide population-based health insurance claims database spanning from January 1, 2000, to December 31, 2017. Each case diagnosed with a pathogenic infection was matched with a corresponding control using propensity scores. We excluded individuals under 20 years of age, those with a history of pathogenic infections before the index date, or those with more than one potential pathogen. To estimate hazard ratios (HR) and the adjusted hazard ratio (aHR) with their respective 95 % confidence intervals (CI), we applied univariable and multivariable Cox proportional hazard models. The multivariable analysis incorporated adjustments for age, sex, and comorbidity-related confounders. RESULTS: The relationship between infection and the subsequent risk of CFS was assessed using Cox proportional hazards regression analysis. The incidence density rates were 6.13 and 8.70 per 1000 person-years among the non-pulmonary infection and pulmonary infection populations, respectively (adjusted hazard ratio [HR] = 1.4, 95 % confidence interval [CI] 1.32-1.5). Patients infected with Pseudomonas, Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, and influenza virus exhibited a significantly higher risk of CFS than those without these pathogens (p < 0.05). Additionally, patients with pneumonia had a significantly increased risk of thromboembolism compare with control group (p < 0.05).

Structural Variances in Curcumin Degradants: Impact on Obesity in Mice.

Some thermal degradants of curcuminoids have demonstrated moderate health benefits in previous studies. Feruloyl acetone (FER), recently identified as a thermal degradant of curcumin, has been previously associated with anticancer and antioxidative effects, yet its other capabilities remain unexplored. Moreover, earlier reports suggest that methoxy groups on the aromatic ring may influence the functionality of the curcuminoids. To address these gaps, an animal study was conducted to investigate the antiobesity effects of both FER and its demethoxy counterpart (DFER) on mice subjected to a high-fat diet. The results demonstrated the significant prevention of weight gain and enlargement of the liver and various adipose tissues by both samples. Furthermore, these supplements exhibited a lipid regulatory effect in the liver through the adiponectin/AMPK/SIRT1 pathway, promoted thermogenesis via AMPK/PGC-1α activation, and positively influenced gut-microbial-produced short-chain fatty acid (SCFA) levels. Notably, DFER demonstrated superior overall efficacy in combating obesity, while FER displayed a significant effect in modulating inflammatory responses. It is considered that SCFA may be responsible for the distinct effects of FER and DFER in the animal study. Future studies are anticipated to delve into the efficacy of curcuminoid degradants, encompassing toxicity and pharmacokinetic evaluations.

Prevention and management of cytomegalovirus infection and disease in kidney transplant: A consensus statement of the Transplantation Society of Taiwan.

Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care.

Oral administration of Lactobacillus delbrueckii subsp. lactis LDL557 attenuates airway inflammation and changes the gut microbiota in a Der p-sensitized mouse model of allergic asthma.

BACKGROUND: Lactic acid bacteria may be used as probiotics to prevent or treat various diseases, and Lactobacillus delbrueckii has an inhibitory effect on the development of atopic diseases. OBJECTIVE: This study explored the effects of L. delbrueckii subsp. lactis strain LDL557 administration on a mouse asthma model resulting from Dermatophoides pteronyssinus (Der p) sensitization and investigated the associated gut microbiota. METHODS: Der p-sensitized and challenged BALB/c mice were orally administered with three different doses of live (low, 107 colony-forming units (CFU); medium, 108 CFU; high, 109 CFU) and heat-killed (109 cells) LDL557 in 200 µL of PBS daily, starting 2 weeks before Der p sensitization and lasting 4 weeks. After the allergen challenge, airway responsiveness to methacholine and the influx of inflammatory cells to the lungs were assessed. The gut microbiome was obtained by sequencing the V3-V4 region of the 16S rRNA gene from mice stool samples. RESULTS: LDL557 in the live (109 CFU) and heat-killed (109 cells) conditions reduced the airway hyper-responsiveness after stimulation with methacholine, inflammatory cell infiltration, and mucus production. These effects were similar to those in groups treated with dexamethasone. No significant change in the gut microbiota was observed after LDL557 treatment, except for the tendency of heat-killed LDL557 to change the gut microbial profile to a greater extent than live LDL557. CONCLUSION: In summary, we found that live and heat-killed LDL557 had the beneficial effect of preventing Der p-induced allergic inflammation in a mouse model of asthma.

Selenite selectively kills lung fibroblasts to treat bleomycin-induced pulmonary fibrosis.

BACKGROUND: Interstitial lung disease (ILD) treatment is a critical unmet need. Selenium is an essential trace element for human life and an antioxidant that activates glutathione, but the gap between its necessity and its toxicity is small and requires special attention. Whether selenium can be used in the treatment of ILD remains unclear. METHODS: We investigated the prophylactic and therapeutic effects of selenite, a selenium derivative, in ILD using a murine model of bleomycin-induced idiopathic pulmonary fibrosis (IPF). We further elucidated the underlying mechanism using in vitro cell models and examined their relevance in human tissue specimens. The therapeutic effect of selenite in bleomycin-administered mice was assessed by respiratory function and histochemical changes. Selenite-induced apoptosis and reactive oxygen species (ROS) production in murine lung fibroblasts were measured. RESULTS: Selenite, administered 1 day (inflammation phase) or 8 days (fibrotic phase) after bleomycin, prevented and treated deterioration of lung function and pulmonary fibrosis in mice. Mechanistically, selenite inhibited the proliferation and induced apoptosis of murine lung fibroblasts after bleomycin treatment both in vitro and in vivo. In addition, selenite upregulated glutathione reductase (GR) and thioredoxin reductase (TrxR) in murine lung fibroblasts, but not in lung epithelial cells, upon bleomycin treatment. GR and TrxR inhibition eliminates the therapeutic effects of selenite. Furthermore, we found that GR and TrxR were upregulated in the human lung fibroblasts of IPF patient samples. CONCLUSIONS: Selenite induces ROS production and apoptosis in murine lung fibroblasts through GR and TrxR upregulation, thereby providing a therapeutic effect in bleomycin-induced IPF.

The Evolution of Upper Tract Urothelial Carcinoma Management in Kidney Recipients.

INTRODUCTION: Urothelial cancers were one of the most common malignancies in patients with kidney transplants. Although radical nephroureterectomy is still the standard of care in current guidelines, studies have shown that significantly improved perioperative outcomes can be achieved for patients who underwent bilateral nephroureterectomy. Our study provides evidence on the outcome of bilateral nephroureterectomy and unilateral nephroureterectomy in kidney recipients with upper tract urothelial carcinoma. MATERIAL AND METHODS: In the study, the data of patients from a single center, Chang Gung Memorial Hospital Linkou branch, were collected retrospectively from 1981 to 2023. The patient's detailed information was collected through the medical records in the hospital. RESULTS: A total of 44 cases of kidney recipients with upper urinary tract urothelial carcinoma were collected in this study. Of the patients, 19 nephroureterectomies were performed before 2008 and 24 afterward. Incidental findings of contralateral tumors were noted in 3 out of 6 patients who underwent bilateral nephroureterectomy before 2008 and 3 out of 12 after 2008. Contralateral upper urinary tract urothelial carcinoma after unilateral nephroureterectomy was noted in 3 patients within a median of 8.1 years. The progression-free survival of bilateral nephroureterectomy was significantly better compared with a unilateral group (not reached, 15.8 years, respectively). DISCUSSION: Our study, along with previous studies, provides evidence that bilateral nephroureterectomy may be a better treatment option in kidney recipients with upper tract urothelial carcinoma. Our study has several limitations based on its retrospective nature.

Long-term follow-up of non-myasthenic patients with early-stage thymoma who underwent extended thymectomy or limited resection.

BACKGROUD: The standard resection for early-stage thymoma is total thymectomy and complete tumour excision with or without myasthenia gravis but the optimal surgery mode for patients with early-stage non-myasthenic thymoma is debatable. This study analysed the oncological outcomes for non-myasthenic patients with early-stage thymoma treated by thymectomy or limited resection in the long term. METHODS: Patients who had resections of thymic neoplasms at Taipei Veteran General Hospital, Taiwan between December 1997 and March 2013 were recruited, exclusive of those combined clinical evidence of myasthenia gravis were reviewed. A total of 113 patients were retrospectively reviewed with pathologic early stage (Masaoka stage I and II) thymoma who underwent limited resection or extended thymectomy to compare their long-term oncologic and surgical outcomes. RESULTS: The median observation time was 134.1 months [interquartile range (IQR) 90.7-176.1 months]. In our cohort, 52 patients underwent extended thymectomy and 61 patients underwent limited resection. Shorter duration of surgery (p < 0.001) and length of stay (p = 0.006) were demonstrated in limited resection group. Six patients experienced thymoma recurrence, two of which had combined myasthenia gravis development after recurrence. There was no significant difference (p = 0.851) in freedom-from-recurrence, with similar 10-year freedom-from-recurrence rates between the limited resection group (96.2 %) and the thymectomy group (93.2 %). Tumour-related survival was also not significantly different between groups (p = 0.726).result CONCLUSION: Patients with early-stage non-myasthenic thymoma who underwent limited resection without complete excision of the thymus achieved similar oncologic outcomes during the long-term follow-up and better peri-operative results compared to those who underwent thymectomy.

Festivity: The Effects of Traditional Holidays on the Graft Function Among Stable Kidney Recipients.

PURPOSE: We observed transient elevations in creatinine levels among kidney recipients after three traditional holidays in Taiwan. This retrospective cohort study aimed to compare the changes in eGFR levels after Chinese New Year, Dragon Boat Festival, and Mid-Autumn Festival, all of which are associated with high-calorie and high-fat diets. MATERIALS AND METHODS: We conducted a retrospective analysis of 364 kidney recipients with stable graft function who were following at Chang Gung Memorial Hospital Linkou from 2018 to 2020. The graft function before and after the festival was determined by calculating the eGFR level using the serum creatinine measured during clinic visits prior to and following the festival. The patients were then categorized into subgroups based on their sex, BMI, and co-morbidities. The eGFR levels before and after the festival were evaluated and compared within these subgroups. RESULTS: A total of 301 kidney recipients have been finally included in this retrospective cohort study. The analysis showed a significant decrease in overall eGFR levels after Chinese New Year (from 56.92 ± 29.70 to 55.14 ± 24.79, P = .006), Mid-Autumn Festival (from 54.03 ± 24.61 to 53.35 ± 24.33, P = .008), and Dragon Boat Festival only in 2020 (from 50.98 ± 24.35 to 49.99 ± 23.45, P = .018). The analysis of subgroups suggested a tendency of renal function decline after all 3 traditional holidays in patient groups with DM or hypertension or nonoverweight status. CONCLUSION: In this study, we observed a significant decline in renal function among kidney recipients following traditional holidays in Taiwan, particularly among recipients with hypertension or diabetes mellitus or those who were not overweight.

Prediction of Early Kidney Transplant Graft Outcome: Insulin Resistance Index.

BACKGROUND: New-onset diabetes after transplantation and increased insulin resistance have both been shown to affect graft performance and survival after kidney transplantation. Thus, we aimed to evaluate the predictive roles of different insulin resistance indices on early graft function in kidney transplant recipients. MATERIALS AND METHODS: We conducted a retrospective analysis of non-diabetic patients who received kidney transplantation between January 1, 2018 and December 31, 2021. The primary outcome was the predictive role of different insulin resistance indices on early graft function of serum creatinine level and estimated glomerular filtration rate at 1, 3, 6, and 12 months. The secondary outcome analyzed was the possible clinical predictive factors for poor kidney graft function at 12 months. RESULTS: Among 123 kidney transplantation patients, stratification with homeostatic model assessment for insulin resistance showed no significant difference in kidney graft function outcome at 1, 3, 6, and 12 months. However, patients with a higher insulin-to-glucose ratio exhibited a significantly higher serum creatinine level at 3 and 6 months and a significantly lower estimated glomerular filtration rate level at 3, 6, and 12 months. Using multivariate logistic regression analysis, patients with a higher insulin-to-glucose ratio were associated with a poorer kidney graft function 12 months after transplantation. CONCLUSION: Patients with a higher baseline insulin resistance with an insulin-to-glucose ratio ≥of 0.092 exhibited a significantly worse early kidney graft function. Thus, with the identification of patients with increased insulin resistance, early intervention, and preventive measures can be implemented to enhance graft performance further.

Sugammadex shortens operation time and improves operation turnover efficacy in video-assisted thoracoscopic surgery.

BACKGROUND: This study compared sugammadex and neostigmine as agents for routine neuromuscular blockade reversal in video-assisted thoracoscopic surgery (VATS) to determine the optimal choice that achieves a shorter operation time and improved turnover efficiency while enhancing postoperative outcomes and ensuring patient safety during thoracic surgery. METHODS: This prospective study, conducted from July 2022 to March 2023, compared the effect of sugammadex and neostigmine on operation time and turnover efficiency in VATS, involving 60 participants randomly assigned to either group, with the primary objective of identifying the optimal anesthesia reversal choice for improved outcomes and patient safety during thoracic surgery. RESULTS: In the study, the sugammadex group showed a significantly shorter total operation room occupancy time (130 ± 7 vs 157 ± 7 minutes; p = 0.009) than the neostigmine group. Patients in the neostigmine group had higher mean pulse rates when leaving the operation room (85 ± 3 vs 73 ± 3 beats/min; p = 0.002) and 120 minutes later in the postanesthesia care unit (76 ± 2 vs 68 ± 2; p = 0.016). CONCLUSION: This study's findings suggest that sugammadex may enhance total operating room occupancy time, operation turnover efficacy, and respiratory recovery outcomes in VATS, potentially improving patient care and anesthesia management.

A multiomic investigation of lung adenocarcinoma molecular subtypes.

BACKGROUND: Lung adenocarcinoma-an aggressive and life-threatening malignancy-is a type of non-small-cell lung cancer. Despite medical advancements, the prognosis of lung adenocarcinoma remains unfavorable, likely because of its heterogeneous nature. Furthermore, few subtype-specific treatments are available for lung adenocarcinoma. This study was conducted to explore the molecular subtypes of lung adenocarcinoma. METHODS: We performed a joint analysis of transcriptome and proteome data from East Asian patients with lung adenocarcinoma (nonsmokers, 86.5%). RESULTS: Four novel subtypes were identified based on distinct molecular characteristics: subtypes I, II, III, and IV. In patients with subtype I lung adenocarcinoma, eukaryotic translation initiation factor 4 gamma 1 activates cell proliferation; inhibiting this factor suppresses tumor growth, and reducing its level induces autophagy. Subtype II is characterized by Kristen rat sarcoma viral oncogene homolog-activating oncogenesis; the onset age of this subtype is the lowest among all subtypes. Subtype III manifests as an advanced disease at diagnosis; it is characterized by a core serum response-related oncogenic signature, which indicates poor overall survival in Western patients with lung cancer. Subtype IV is more common in men than in women; it has astroglial characteristics. A Connectivity Map analysis revealed that the oncogenic expression patterns corresponding to subtypes I, II, III, and IV can be reversed by the inhibitors of Inhibitor of κB (IκB) kinase (eg, withaferin A), mammalian target of rapamycin (eg, everolimus), Src proto-oncogene (Src) (eg, saracatinib), and Transforming Growth Factor (TGF)-ß/Smad (eg, LY-364947), respectively. CONCLUSION: This study introduced an innovative multiomics data analysis pipeline. Using this approach, we successfully identified four molecular subtypes of lung adenocarcinoma and their candidate therapeutic agents. The newly identified subtypes can be combined with the current biomarkers to generate a comprehensive roadmap for treatment decision-making.

Opposite effects of RWA and SDO on war support: Chinese public opinion toward Russia's war in Ukraine.

Previous research has identified the combined effects of Right-Wing Authoritarianism (RWA) and Social Dominance Orientation (SDO) on individuals' militant attitudes. Much of the existing studies have been conducted in the United States and Europe, where political cleavage is drawn between liberalism and conservatism and where RWA and SDO are aligned with conservatism. In this article, we argue that in a different ideological backdrop where RWA and SDO are not bound by conservative ideology, their influence on war support varies. We use the case study of China, in which socialist ideology upholds authoritarianism but opposes social dominance. We hypothesize that in a war in which the state acquiesces, regime loyalists high on RWA and low on SDO tend to back the war, while regime critics low on RWA and high on SDO are less supportive. Using longitudinal data with a nationwide online sample (Time 1: N = 1000, Time 2: N = 500) collected during the war in Ukraine, we confirmed the opposite effects of RWA (measured by the traditionalism subscale) and SDO (measured by the dominance subscale) on war support. The findings extend our understanding of the impacts of authoritarianism and social dominance in a context beyond the United States and Europe.

Prognostic factors for recurrence-free survival in resected pathologic N2-stage III non-small cell lung cancer treated with upfront surgery.

BACKGROUND: The standard treatment for pathological N2 (pN2) non-small-cell lung cancer (NSCLC) patients is definitive chemoradiation. Surgery might be beneficial for resectable pN2 disease, so we investigated the recurrence-free interval of upfront surgery for selected patients with resectable pN2 disease. METHODS: The clinicopathologic characteristics of patients with pN2 NSCLC who underwent upfront anatomical resection at Taipei Veterans General Hospital from 2011 January to 2019 December were retrospectively reviewed. A Cox regression model was used to identify prognostic factors of recurrence-free survival (RFS). RESULTS: In total, 84 patients after curative lung anatomic resection were analyzed, with a 44-month median survival. The 1-, 3-, and 5-year RFS rates were 63.1%, 31.3%, and 19.9%, respectively, with a median RFS of 18.9 months. Multivariable cox regression analysis identified that the significant predictor for RFS was a tumor size of more than 3 cm (hazard ratio [HR] = 1.74, 95% CI, 1.07-2.83, p = 0.027). Visceral pleural invasion, LN harvest number, tumor stage, and N2 status including single zone (N2a) or multiple zones (N2b) were not prognostic factors in this study. CONCLUSION: Upfront surgery for resectable N2 disease achieved favorable outcomes in selected patients, especially better recurrence control with limited tumor size. Therapeutic advances might encourage surgeons to aggressive intervention.

Bimetallic nickel complexes containing imidazole-based phenolate ligands as efficient catalysts for the copolymerization of carbon dioxide with epoxides.

The utilization of hexadentate imidazole-derived diamine-bisphenolate ligands to construct structurally well-defined bimetallic nickel catalysts that enable the mediation of the copolymerization of carbon dioxide with alicyclic epoxides was reported for the first time. A series of dinickel carboxylate/nitrophenolate complexes were facilely prepared through a one-pot procedure and their structures were fully determined by single crystal X-ray structural analysis. Dinickel complexes 1-10 were used as single-component catalysts, and were evaluated for the copolymerization of CO2 and cyclohexene oxide (CHO), for which acetato-incorporated complex 1 was proved to exhibit the best activity. Not only has the controllability of binickel catalyst 1 for CO2/CHO copolymerization been demonstrated, but also an "immortal" character for the same polymerization has been realized. Furthermore, detailed kinetic studies of polymerization catalysis of this type were undertaken, and the kinetics results revealed a first-order dependence on both Ni complex 1 and CHO concentrations. This is a successful example of the introduction of the easily accessible nitrogen-heterocycle group, the imidazole moiety, into phenolate ligands for the development of high-performance homogeneous catalysts towards the bimetallic complex-catalyzed copolymerization of CO2 and epoxides.

A combination of oxygenation and driving pressure can provide valuable information in predicting the risk of mortality in ARDS patients.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common life-threatening condition in critically ill patients. Itis also an important public health issue because it can cause substantial mortality and health care burden worldwide. The objective of this study was to investigate therisk factors that impact ARDS mortality in a medical center in Taiwan. METHODS: This was a single center, observational study thatretrospectively analyzed data from adults in 6 intensive care units (ICUs) at Taichung Veterans General Hospital in Taiwan from 1st October, 2018to30th September, 2019. Patients needing invasive mechanical ventilation and meeting the Berlin definition criteria were included for analysis. RESULTS: A total of 1,778 subjects were screened in 6 adult ICUs and 370 patients fulfilled the criteria of ARDS in the first 24 hours of the ICU admission. Among these patients, the prevalenceof ARDS was 20.8% and the overall hospital mortality rate was 42.2%. The mortality rates of mild, moderate and severe ARDS were 35.9%, 43.9% and 46.5%, respectively. In a multivariate logistic regression model, combination of driving pressure (DP) > 14cmH2O and oxygenation (P/F ratio)≤150 was an independent predictor of mortality (OR2.497, 95% CI 1.201-5.191, p = 0.014). Patients with worse oxygenation and a higher driving pressure had the highest hospital mortality rate(p<0.0001). CONCLUSIONS: ARDS is common in ICUs and the mortality rate remains high. Combining oxygenation and respiratory mechanics may better predict the outcomes of these ARDS patients.

Genetic Susceptibility of HLA Alleles to Non-Steroidal Anti-Inflammatory Drug Hypersensitivity in the Taiwanese Population.

BACKGROUND: Human leukocyte antigen (HLA) genes are important in many immune processes and contribute to many adverse drug reactions. Whether genetic variations in the HLA region are associated with non-steroid anti-inflammatory drug (NSAID) hypersensitivity remains uncertain. Therefore, the aim of our study was to identify HLA genetic variations in patients with NSAID hypersensitivity in the Taiwanese population. METHODS: This hospital-based, retrospective case-control study enrolled 37,156 participants with NSAID exposure from the Taiwan Precision Medicine Initiative (TPMI), who were all genotyped and imputed to fine map HLA typing. Our study assigned 1217 cases to the NSAID allergy group and 12,170 controls to a matched group. Logistic regression analyses were utilized to explore associations between HLA alleles and NSAID hypersensitivity. RESULTS: Overall, 13,387 patients were genotyped for eight major HLA alleles. Allele frequencies were different between the two groups. In the NSAID allergy group, the genotype frequencies of HLA-A*02:01, HLA-A*34:01, and HLA-DQA1*06:01 were found to be markedly elevated compared to the control group, a significance that persisted even after applying the Bonferroni correction. Furthermore, the risk of NSAID allergy demonstrated a significant association with HLA-A*02:01 (OR = 1.29, p < 0.001) and HLA-A*34:01 (OR = 9.90, p = 0.001), in comparison to their respective counterparts. Notably, the genotype frequency of HLA-B*46:01 exhibited a significant increase in the severe allergy group when compared with the mild allergy group. CONCLUSIONS: We identified HLA genotypes linked to the onset and severity of NSAID hypersensitivity. Our findings establish a basis for precision prescription in future clinical applications.

Treatment Outcomes and Risk Factors for Incomplete Treatment after Definitive Chemoradiotherapy for Non-Resectable or Metastatic Esophageal Cancer.

Among patients with unresectable or metastatic esophageal cancer who receive definitive chemotherapy or chemoradiotherapy, the rates of treatment-related adverse events and incomplete treatment remain high. We conducted this study to investigate survival after definitive treatments and identify predicting factors for incomplete treatment. The data of patients who received definitive chemotherapy or chemoradiotherapy for esophageal cancer were retrospectively examined. The patients were assigned to Group 1: incomplete definitive treatment; Group 2: complete definitive treatment; or Group 3: complete definitive treatment with additional salvage surgery. The data of 273 patients (90, 166, and 17 in Groups 1, 2, and 3, respectively) were analyzed. In the survival analysis, the median overall survival of Groups 1, 2, and 3 were 2.6, 10.3, and 29.5 months, respectively. A significant difference in 3-year overall survival was observed among the groups (2.2%, 12.4%, and 48.5%, p < 0.001). In multivariable analysis, the independent risk factors for incomplete definitive treatment included poor performance score (hazard ratio (HR): 5.23, p = 0.001), bone metastasis (HR: 2.18, p = 0.024), airway invasion (HR: 2.90, p = 0.001), and liver cirrhosis (HR: 3.20, p = 0.026). Incomplete definitive treatment is associated with a far worse prognosis. Poor performance, bone metastasis, airway invasion, and liver cirrhosis are risk factors for incomplete treatment.

NLRP3 Inflammasome Activates Endothelial-to-Mesenchymal Transition via Focal Adhesion Kinase Pathway in Bleomycin-Induced Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis has poor clinical outcomes despite antifibrotic treatment. The nucleotide-binding domain leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3) inflammasome and endothelial-to-mesenchymal transition (EndoMT) were shown to be involved in the pathogenesis of pulmonary fibrosis. However, the detailed mechanism is unknown. Our study aimed to investigate the role of the NLRP3 inflammasome in the regulation of EndoMT in pulmonary fibrosis. The inhibition of the NLRP3 inflammasome via a caspase-1 inhibitor, Ac-YVAD-cmk (YVAD), was intraperitoneally administered to male C57BL/6 mice (8-12 weeks old) one hour before bleomycin intratracheal injection (1.5 U/kg). Immunohistochemical staining, Masson's trichrome staining, enzyme-linked immunosorbent assay, immunofluorescence, and Western blotting were used to assess the activity of the NLRP3 inflammasome and EndoMT in lung samples from mice. Human pulmonary microvascular endothelial cells (HPMECs) were used as a model of EndoMT in vitro with YVAD and bleomycin stimulation. We observed the activation of the NLRP3 inflammasome and EndoMT (decreased vascular endothelial cadherin with increased alpha-smooth muscle actin and vimentin) in the lung samples after bleomycin. However, inhibition of the NLRP3 inflammasome significantly reduces EndoMT via inhibiting focal adhesion kinase (FAK). In vitro studies also confirmed these findings. In conclusion, NLRP3 inflammasome inhibition could reduce lung inflammation and fibrosis via the regulation of EndoMT by the FAK pathway.