Heat-related illness and dementia: a study integrating epidemiological and experimental evidence.

BACKGROUND: Heat-related illness (HRI) is commonly considered an acute condition, and its potential long-term consequences are not well understood. We conducted a population-based cohort study and an animal experiment to evaluate whether HRI is associated with dementia later in life. METHODS: The Taiwan National Health Insurance Research Database was used in the epidemiological study. We identified newly diagnosed HRI patients between 2001 and 2015, but excluded those with any pre-existing dementia, as the study cohort. Through matching by age, sex, and the index date with the study cohort, we selected individuals without HRI and without any pre-existing dementia as a comparison cohort at a 1:4 ratio. We followed each cohort member until the end of 2018 and compared the risk between the two cohorts using Cox proportional hazards regression models. In the animal experiment, we used a rat model to assess cognitive functions and the histopathological changes in the hippocampus after a heat stroke event. RESULTS: In the epidemiological study, the study cohort consisted of 70,721 HRI patients and the comparison cohort consisted of 282,884 individuals without HRI. After adjusting for potential confounders, the HRI patients had a higher risk of dementia (adjusted hazard ratio [AHR] = 1.24; 95% confidence interval [CI]: 1.19-1.29). Patients with heat stroke had a higher risk of dementia compared with individuals without HRI (AHR = 1.26; 95% CI: 1.18-1.34). In the animal experiment, we found cognitive dysfunction evidenced by animal behavioral tests and observed remarkable neuronal damage, degeneration, apoptosis, and amyloid plaque deposition in the hippocampus after a heat stroke event. CONCLUSIONS: Our epidemiological study indicated that HRI elevated the risk of dementia. This finding was substantiated by the histopathological features observed in the hippocampus, along with the cognitive impairments detected, in the experimental heat stroke rat model.

Gestational age-specific reference intervals for androgens in pregnancy.

BACKGROUND: Androgen could impact cervical remodelling during pregnancy, and a higher level is associated with adverse pregnancy outcomes. A population-based gestation age-specific reference interval (RI) of total testosterone (TT), androstenedione (A4), and 17-hydroxyprogesterone (17-OHP) can help to diagnose maternal hyperandrogenism. METHODS: We enrolled 600 healthy Chinese women to obtain longitudinal serum samples across gestation. The serum androgen profile was measured by liquid chromatography-tandem mass spectrometry. The equations for medians of TT, A4, and 17-OHP were generated by MedCal, and the variances adjusted for 2-level modeling were generated by MLwiN, a system for the specification and analysis of a range of multilevel models. RESULTS: A4 and TT levels increased across the gestation, and they closely correlated with each other (R = 0.90, P=<0.001), whereas 17-OHP level decreased from 5th gestational week to 16th gestational week and then increased afterward towards the end of pregnancy. Women diagnosed with preeclampsia (PE) were found to have a significantly higher level of A4, TT, and 17-OHP when compared with non-PE cases with p ≤0.01, whereas mothers carrying male versus female fetuses have comparable levels of A4, TT, and 17-OHP. CONCLUSION: The study highlights a methodology for constructing gestational age-specific TT, A4, and 17-OHP levels to provide a better interpretation of results in a cohort of healthy Chinese women. The observation in PE supports previous findings, and the higher levels of TT, A4, and 17-OHP were observed before the onset of PE.

Characteristics of "do not resuscitate" orders among elderly patients receiving mechanical ventilation in the intensive care unit in Taiwan.

Objective: As patient life expectancy has increased and people are living longer than before, the rate of mechanical ventilation among elderly patients in the intensive care unit has increased. Older patients who receive mechanical ventilation and have multiple comorbidities are more likely to have a do not resuscitate order than are younger patients with fewer comorbidities. The aim of our study was to describe the patient characteristics and predictive factors of do not resuscitate orders during hospitalization among elderly patients who received ventilation in the intensive care unit. Methods: This was a retrospective review of the electronic medical records of patients in the intensive care unit of a teaching hospital in southern Taiwan. We enrolled patients admitted to the general intensive care unit from January 1, 2018, to September 31, 2020, and patients older than 80 years who experienced respiratory failure, were intubated and received mechanical ventilation. We analyzed patient demographics, disease severity during hospitalization and comorbidities. If a patient had multiple admissions to the intensive care unit, only the first admission was recorded. Results: Of the 305 patients over 80 years of age with respiratory failure who were intubated and placed on a ventilator, 66 were excluded because of incomplete data, and 13 were excluded because they had already signed a do not resuscitate order prior to admission to the hospital. Ultimately, 226 patients were included in this study. A higher acute physiology and chronic health evaluation II score (>30) was also associated with an increased likelihood of a do not resuscitate order (odds ratio (OR) = 3.85, 95% CI = 1.09-13.62, p = 0.0362). Patients who had acute kidney injury or cerebrovascular accident were more likely to have a do not resuscitate order (OR = 2.74, 95% CI = 1.03-7.28, p = 0.0428 and OR = 7.32, 95% CI = 2.02-26.49, p = 0.0024, respectively). Conclusion: Our study showed that older age, greater disease severity, and certain critical interventions were associated with a greater propensity for do not resuscitate orders, which is crucial for understanding patient preferences and guiding end-of-life care discussions. These findings highlight the importance of clinical severity and specific health events in predicting end-of-life care preferences in older patient groups.

Early outcomes of the Oxford unicompartmental knee arthroplasty: 140 cases from a single institute in Taiwan.

BACKGROUND: The clinical and radiologic outcomes of the Oxford unicompartmental knee arthroplasty utilizing Microplasty® instrumentation have not been extensively investigated in Taiwanese patients. Despite the efficacy of this treatment for unicompartmental knee diseases, its specific impact on this population remains unknown. METHODS: We retrospectively analyzed prospectively collected data of patients who underwent OUKA with MP between 2018 and 2021, including demographic information, component position, preoperative and postoperative knee range of motion (ROM), numeric rating scale (NRS), and 2011 Knee Society Score-functional activity score (2011 KSS-FAS). We compared preoperative and postoperative data and analyzed the correlation between clinical and radiographic outcomes. RESULTS: Among 140 patients with an average age of 66.8 years, predominantly female, the majority exhibited components that fell within the radiographically acceptable tolerance ranges. The mean 2.5-year follow-up revealed significant improvements in knee ROM from 102.6° ± 12.9° to 127.3° ± 9.8° ( p < 0.05), pain reduction from 7.7 ± 0.8 to 0.4 ± 0.7 ( p < 0.001), and KSS-FAS from 30.7 ± 10.5 to 94.3 ± 5.2 ( p < 0.001). Notably, a tibial component medial overhang within tolerance predicted shorter hospital stays, and a higher preoperative KSS correlated with lower postoperative NRS. No independent variables were identified as predictors of a higher postoperative KSS. CONCLUSION: Our study on OUKA with MP in Taiwanese patients reveals promising early clinical and radiographic outcomes. Tibial component medial overhang <3 mm is associated with shorter hospital stays, and a higher preoperative KSS predicts lower NRS at 1 year postoperatively.

Shock index to predict outcomes in patients with trauma following traffic collisions: a retrospective cohort study.

PURPOSE: Taiwan, which has a rate of high vehicle ownership, faces significant challenges in managing trauma caused by traffic collisions. In Taiwan, traffic collisions contribute significantly to morbidity and mortality, with a high incidence of severe bleeding trauma. The shock index (SI) and the modified shock index (MSI) have been proposed as early indicators of hemodynamic instability. In this study, we aimed to assess the efficacy of SI and MSI in predicting adverse outcomes in patients with trauma following traffic collisions. METHODS: This retrospective cohort study was conducted at Chi Mei Hospital from January 2015 to December 2020. The comprehensive analysis included 662 patients, with data collected on vital signs and outcomes such as mortality, blood transfusion, emergent surgical intervention (ESI), transarterial embolization (TAE), and intensive care unit (ICU) admission. Optimal cutoff points for SI and MSI were identified by calculating the Youden index. Logistic regression analysis was used to assess outcomes, adjusting for demographic and injury severity variables. RESULTS: An SI threshold of 1.11 was associated with an increased risk of mortality, while an SI of 0.84 predicted the need for blood transfusion in the context of traffic collisions. Both SI and MSI demonstrated high predictive power for mortality and blood transfusion, with acceptable accuracy for TAE, ESI, and ICU admission. Logistic regression analyses confirmed the independence of SI and MSI as risk factors for adverse outcomes, thus, providing valuable insights into their clinical utility. CONCLUSIONS: SI and MSI are valuable tools for predicting mortality and blood transfusion needs in patients with trauma due to traffic collisions. These findings advance the quality of care for patients with trauma during their transition from the emergency room to the ICU, facilitating prompt and reliable decision-making processes and improving the care of patients with trauma.

Risk of Atrial Fibrillation in Patients with Different Cancer Types in Taiwan.

Atrial fibrillation (AF) commonly occurs in approximately 2% of cancer patients, and the incidence of AF among cancer patients is greater than in the general population. This observational study presented the incidence risk of AF among cancer patients, including specific cancer types, using a population database. The Taiwan Cancer Registry was used to identify cancer patients between 2008 and 2017. The diagnosis of AF was based on the International Classification of Diseases codes (ICD-9-CM: 427.31 or ICD-10-CM: I48.0, I48.1, I48.2, and I48.91) in Taiwan national health insurance research datasets. The incidence of developing AF in the cancer population was calculated as the number of new-onset AF cases per person-year of follow-up during the study period. The overall incidence of AF among cancer patients was 50.99 per 100,000 person-years. Patients aged older than 65 years and males had higher AF incidence rates. Lung cancer males and esophageal cancer females showed the highest AF incidence risk (185.02 and 150.30 per 100,000 person-years, respectively). Our findings identified esophageal, lung, and gallbladder cancers as the top three cancers associated with a higher incidence of AF. Careful monitoring and management of patients with these cancers are crucial for early detection and intervention of AF.

The role of adjuvant radiotherapy for intracranial malignant meningiomas: analysis of a nationwide database.

PURPOSE: This study aimed to examine the effect of postoperative radiotherapy on survival outcomes in patients with malignant meningiomas. METHODS: We identified patients with malignant meningioma diagnosed between 2007 and 2018 using the Taiwan Cancer Registry and followed them up using the death registry. Survival was compared between patients with and without adjuvant radiotherapy. The potential confounding factors evaluated in this study included age, sex, comorbidities, and the Charlson Comorbidity Index (CCI). RESULTS: The analysis included 204 patients; 94 (46%) received adjuvant radiotherapy. The two groups had similar sex distributions (p = 0.53), mean age (p = 0.33), histologic subtype (p = 0.13), and CCI (p = 0.62). The prognosis of malignant meningioma was poor, with a median overall survival (OS) of 2.4 years. The median OS was 3.0 years (interquartile range (IQR) [1.4-6.1], and 2.0 years (IQR [0.5-3.9]) in the radiotherapy and non-radiotherapy groups, respectively (p = 0.001). However, Kaplan-Meier curves with the log-rank test showed no significant difference in OS between the two groups (p = 0.999). Controlling for age group, sex, histologic subtype, treatment, comorbidities, and CCI, adjuvant radiotherapy did not impart a survival benefit (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.6‒1.26); however, only factor of higher comorbidity score (HR = 2.03, 95%CI: 1.04‒3.94) was associated with unfavorable survival. CONCLUSION: This population-based retrospective analysis suggests that the role of radiotherapy remains unclear and underscores the need for randomized clinical trials to assess the usefulness of adjuvant radiotherapy in malignant meningioma.

Association between Sjögren syndrome, sociodemographic factors, comorbid conditions, and optic neuritis: a Taiwanese population-based study.

Purpose: Our study aimed to explore the correlation between Sjögren syndrome, sociodemographic factors, comorbid conditions, and optic neuritis. Methods: This retrospective, nationwide, population-based, matched case-control investigation involved 33,190 individuals diagnosed with optic neuritis, identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes 377.30 for optic neuritis or 377.32 for retrobulbar neuritis. Patient data were extracted from the Taiwan National Health Insurance Research Database. Demographic characteristics, the presence of Sjögren syndrome, and pre-existing comorbid conditions were analyzed using univariate logistic regression. Continuous variables were assessed with a paired t-test. Adjusted logistic regression was employed to compare the prognosis odds ratio (OR) of patients with optic neuritis to controls. Results: After adjusting for confounding variables, individuals with Sjögren syndrome exhibited a significantly higher likelihood of developing optic neuritis compared to controls (adjusted OR, 9.79; 95% confidence interval [CI], 7.28-12.98; p < 0.0001). Other conditions associated with increased odds of optic neuritis included rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus, and granulomatous vasculitis (adjusted OR: 1.57, 95% CI: 1.33-1.86; adjusted OR: 2.02, 95% CI: 1.65-2.48; adjusted OR: 140.77, 95% CI: 35.02-565.85; adjusted OR: 2.38, 95% CI: 1.71-3.30; adjusted OR: 18.28, 95% CI: 2.21-151.45, respectively), as well as systemic infections such as human herpes viral infection and tuberculosis infection (adjusted OR: 1.50, 95% CI: 1.35-1.66; adjusted OR: 4.60, 95% CI: 3.81-5.56, respectively). Discussion: Our findings strongly support the existence of an association between Sjögren syndrome, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus, granulomatous vasculitis, human herpes viral infection, tuberculosis, and optic neuritis.

Retinoblastoma Incidence in Taiwan Over a Recent 20-Year Period: A Comprehensive Nationwide Study.

Purpose: Continuous advancements in medical diagnostic technology and the growing availability of resources suggest a potential for fluctuations in the incidence rate of retinoblastoma (Rb). This study aimed to analyze incidence data of Rb patients in Taiwan from 1999 to 2018, utilizing the nationwide Taiwan Cancer Registry (TCR) database. Additionally, we investigated the treatment modalities used for these Rb patients and compared them with those observed in other countries. Patients and Methods: We conducted a retrospective cohort study utilizing data from the TCR database. The study cohort comprised individuals who were newly diagnosed with Rb between 1999 and 2018. The incidence of Rb was calculated as the number of patients with Rb per million live births, both for the entire population and for different gender groups and time periods. The trends in Rb incidence from 1999 to 2018 across various age groups and sexes were presented with the linear trend test. Results: From 1999 to 2018, a total of 248 cases of Rb were identified. The overall incidence rate over this 20-year period was 60.20 cases per million live births, corresponding to 1 case per 16,611 live births. Incidence rates for each 5-year period between 1999 and 2018 exhibited no significant differences. The study cohort was predominantly male, with 134 cases (54.03%) being males and 114 cases (45.97%) being females, resulting in an overall male-to-female sex ratio of 1.18. Females had lower relative risk than males (RR: 0.92, 95% CI: 0.72-1.19). Primary surgical intervention was the preferred treatment modality for over 75% of the cases. Conclusion: This retrospective epidemiology study, using TCR from 1999 to 2018, indicated that no discernible trend of retinoblastoma incidence in Taiwan. Nevertheless, continuous monitoring of incidence rates and exploration of treatment strategies for retinoblastoma within the Taiwanese population are important to address potential changes in developing medical practices.

The Efficacy of On-Site Integration Screening and Microelimination Programs for Chronic Hepatitis C in a Detection Center: A Comparison of the Treatment Outcomes and Characteristics of Incarcerated Patients and Outpatients.

We aimed to analyze the different patient characteristics and treatment outcomes (such as sustained viral response, SVR) between incarcerated patients with chronic hepatitis C (CHC) and those with CHC from the outpatient department through an on-site integrated screening and microelimination program in a detection center. In this retrospective study, which ran from May 2021 to April 2022, we included 32 consenting male prisoners aged at least 20 years who were willing to participate in the study. Members of the control group (who received DAAs in an outpatient setting) were selected from the treated CHC patient databank of individuals who received DAA regimens at Chi Mei Hospital between January 2021 and December 2022. The patients in the two groups did not differ significantly in terms of age, FIB-4 score, HCV RNA, HBV coinfection, hemogram findings, coagulation profiles, and renal function tests. However, the patients in the incarcerated group had a significantly different genotype distribution compared to the control group, significantly lower liver enzyme levels, and higher albumin and bilirubin levels compared to those in the control group. The rate of SVR to DAA treatment obtained among incarcerated patients did not differ significantly from that obtained among patients in the control group. Loss to follow-up (for several reasons) is a major reason for treatment discontinuation among these patients.

Expanded Newborn Screening for Inborn Errors of Metabolism in Hong Kong: Results and Outcome of a 7 Year Journey.

Newborn screening (NBS) is an important public health program that aims to identify pre-symptomatic healthy babies that will develop significant disease if left undiagnosed and untreated. The number of conditions being screened globally is expanding rapidly in parallel with advances in technology, diagnosis, and treatment availability for these conditions. In Hong Kong, NBS for inborn errors of metabolism (NBSIEM) began as a pilot program in October 2015 and was implemented to all birthing hospitals within the public healthcare system in phases, with completion in October 2020. The number of conditions screened for increased from 21 to 24 in April 2016 and then to 26 in October 2019. The overall recruitment rate of the NBS program was 99.5%. In the period between October 2015 and December 2022, 125,688 newborns were screened and 295 were referred back for abnormal results. The recall rate was reduced from 0.26% to 0.12% after the implementation of second-tier testing. An inherited metabolic disorder (IMD) was eventually confirmed in 47 infants, making the prevalence of IMD in Hong Kong 1 in 2674. At the time of the NBS result, 78.7% of the newborns with IMD were asymptomatic. There were two deaths reported: one newborn with methylmalonic acidemia cobalamin B type (MMACblB) died after the initial crisis and another case of carnitine palmitoyltransferase II deficiency (CPTII) died at 18 months of age after metabolic decompensation. The most common IMD noted were disorders of fatty acid oxidation metabolism (40%, 19 cases), closely followed by disorders of amino acid metabolism (38%, 18 cases), with carnitine uptake defect (19.1%, 9 cases) and citrullinemia type II (17%, 8 cases) being the two most common IMD picked up by the NBSIEM in Hong Kong. Out of the all the IMDs identified, 19.1% belonged to diverse ethnic groups. False negative cases were reported for citrullinemia type II and congenital adrenal hyperplasia during this period.

Association between statin use and tuberculosis risk in patients with bronchiectasis: a retrospective population-based cohort study in Taiwan.

BACKGROUND: Chronic airway diseases have been associated with an increased risk of tuberculosis (TB); however, data in patients with bronchiectasis is limited. Statins have been shown to exhibit anti-inflammatory effects by modulating the inflammatory response. This study investigated whether statin treatment could reduce the risk of TB in patients with bronchiectasis. METHODS: We conducted a retrospective cohort study using a nationwide population database of patients with bronchiectasis who did or did not receive statin treatment. The defined daily dose (DDD) of statin, current or past statin user and statin exposure time were measured for the impact of statin use. The primary outcome was the incidence of new-onset TB. Considering of potential immortal time bias due to stain exposure time, Cox regression models with time-dependent covariates were employed to estimate HRs with 95% CIs for TB incidence among patients with bronchiectasis. RESULTS: Patients with bronchiectasis receiving statin treatment had a decreased risk of TB. After adjusting for age, sex, income, comorbidities and Charlson Comorbidity Index, statin users had a 0.59-fold lower risk of TB incidence compared with non-statin users (95% CI 0.40 to 0.88; p=0.0087). Additionally, compared with non-statin users, statin treatment was a protective factor against TB in users with a cumulative DDD greater than 180 per year, with an HR of 0.32 (95% CI 0.12 to 0.87; p=0.0255). CONCLUSIONS: Statin treatment demonstrated a dose-dependent protective effect and was associated with a reduced risk of TB in patients with bronchiectasis. These findings suggest that statins may play a role in lowering TB risk by modulating airway inflammation in this patient population.

Comparative survival analysis of bladder preservation therapy versus radical cystectomy in muscle-invasive bladder cancer.

BACKGROUND: Bladder preservation therapy is an alternative to radical cystectomy in patients with muscle-invasive bladder cancer (MIBC). The purpose of this study is to compare survival outcomes between bladder preservation therapy and radical cystectomy in MIBC patients using an Asian nationwide cancer registry database. METHODS: From the Taiwan Cancer Registry database and the Taiwan National Health Insurance Research Database, we identified bladder cancer patients from 2008 to 2018. The patients with urothelial carcinoma and clinical stage T2-T4aN0-1 M0 were included. Propensity score matching by age, gender, clinical stage, cT classification, and Charlson Comorbidity Index score was used between those receiving bladder preservation therapy or radical cystectomy. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared using the Kaplan-Meier method. Multivariate Cox regression models were used to determine the predictive factors of OS, CSS, and DFS. RESULTS: Following the propensity score matching, 393 MIBC patients were analyzed, 131 (33.3%) receiving bladder preservation therapy and 262 (66.7%) receiving radical cystectomy. After 5 years of the follow-up period the overall duration was with a median of 15.6 months. The treatment groups did not differ significantly in OS, CSS, and DFS (p = 0.2681, 0.7208, and 0.3616, respectively). In multivariable Cox regression models, bladder preservation therapy remained non-inferior to radical cystectomy in OS (adjusted hazard ratio [aHR] 1.08; 95% confidence interval [CI], 0.77-1.50; p = 0.6689), CSS (aHR, 1.06; 95% CI, 0.72-1.57; p = 0.7728), and DFS (aHR, 0.76; 95% CI, 0.46-1.27; p = 0.2929). Additionally, among patients ≥80 years, the use of bladder preservation therapy compared with radical cystectomy resulted in an equivalent OS, CSS and DSS. CONCLUSION: In Asian populations, bladder preservation therapy yielded similar survival outcomes as radical cystectomy in MIBC patients. Based on the results, it is evident that a multidisciplinary approach and shared decision-making are recommended for bladder cancer treatment.

The LEAP checklist for laboratory evaluation and analytical performance characteristics reporting of clinical measurement procedures.

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the LEAP checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners.

Aberrant trophoblastic differentiation in human cancer: An emerging novel therapeutic target (Review).

Various types of human cancer may develop aberrant trophoblastic differentiation, including histological changes and altered expression of ß­human chorionic gonadotropin (ß­hCG). Aberrant trophoblastic differentiation in epithelial cancer is usually associated with poor differentiation, tumor metastasis, unfavorable prognosis and treatment resistance. Since ß­hCG­targeting vaccines have failed in an early phase II trial, it is crucial to obtain a better understanding of the molecular pathogenesis of trophoblastic differentiation in human cancer. The present review summarizes the clinical and translational research on this topic with the aim of accelerating the development of an effective targeted therapy. Ectopic expression of ß­hCG promotes proliferation, migration, invasion, vasculogenesis and epithelial­mesenchymal transition (EMT) in vitro, and enhances metastatic and tumorigenic capabilities in vivo. Signaling cascades modulated by ß­hCG include the TGF­ß receptor pathway, EMT­related pathways, the c­MET receptor tyrosine kinase and mitogen­activated protein kinase/ERK pathways, and the SMAD2/4 pathway. Taken together, these findings indicated that TGF­ß receptors, c­MET and ERK1/2 are potential therapeutic targets. Nevertheless, further investigation on the molecular basis of aberrant trophoblastic differentiation is mandatory to improve the design of precision therapy for this aggressive type of human cancer.

A pathologically expanded, clonal lineage of IL-21 producing CD4+ T cells drives Inflammatory neuropathy.

Inflammatory neuropathies, which include CIDP (chronic inflammatory demyelinating polyneuropathy) and GBS (Guillain Barre Syndrome), result from autoimmune destruction of the peripheral nervous system (PNS) and are characterized by progressive weakness and sensory loss. CD4+ T cells play a key role in the autoimmune destruction of the PNS. Yet, key properties of pathogenic CD4+ T cells remain incompletely understood. Here, we use paired scRNAseq and scTCRseq of peripheral nerves from an inflammatory neuropathy mouse model to identify IL-21 expressing CD4+ T cells that are clonally expanded and multifunctional. These IL-21-expressing CD4+ T cells are comprised of two transcriptionally distinct expanded populations, which express genes associated with Tfh and Tph subsets. Remarkably, TCR clonotypes are shared between these two IL-21-expressing populations, suggesting a common lineage differentiation pathway. Finally, we demonstrate that IL-21 signaling is required for neuropathy development and pathogenic T cell infiltration into peripheral nerves. IL-21 signaling upregulates CXCR6, a chemokine receptor that promotes CD4+ T cell localization in peripheral nerves. Together, these findings point to IL-21 signaling, Tfh/Tph differentiation, and CXCR6-mediated cellular localization as potential therapeutic targets in inflammatory neuropathies.

Association of alcohol consumption, betel nut chewing, and cigarette smoking with mortality in patients with head and neck cancer among the Taiwanese population: A nationwide population-based cohort study.

OBJECTIVES: This study investigated the association of alcohol consumption, betel nut chewing, and cigarette smoking (ABC) with mortality in patients with head and neck cancer (HNC). This nationwide population-based cohort study determined whether ABC habits were associated with overall or cancer-specific mortality in patients with HNC in Taiwan. METHODS: Data from the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database were used to identify patients with HNC from 2011 to 2017. All the identified patients were monitored until the date of death or the end of 2017. Poisson regression models were employed to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs) associated with the effect of ABC habits on mortality. RESULTS: A total of 31,246 patients with HNC were analyzed in this study. The results revealed that betel nut chewing alone exhibited the strongest effect, significantly increasing the risk of overall mortality (adjusted IRR = 1.44, 95% CI = 1.27-1.63). Additionally, betel nut chewing alone was significantly associated with cancer-specific mortality (adjusted IRR = 1.51, 95% CI = 1.30-1.44). Stratified analyses by sex and tumor location indicated that the effect of betel nut chewing alone on overall or cancer-specific mortality remained significant across both sexes, and among patients with oral cancer and patients with oropharyngeal cancer. CONCLUSIONS: ABC habits, particularly betel nut chewing, are significantly associated with diminished survival rates in patients with HNC. Accordingly, the implementation of an integrated campaign targeting the prevention of betel nut chewing would be one of the effective public health strategies for improving outcomes for HNC patients.

Review on the screening of urine glucose for early diagnosis of type 2 diabetes mellitus in school children and adolescents with obesity in Hong Kong.

OBJECTIVES: Obesity and type 2 diabetes mellitus (T2DM) are growing health concerns. Since 2005, Student Health Service (SHS) and Hong Kong Paediatric Society formulated a protocol on urine glucose screening (UGS) for early diagnosis of T2DM in students with obesity in Hong Kong. This study reviews students with T2DM captured by this screening program and compare the data with the Hong Kong Children Diabetes Registry (HKCDR) database, to see if the UGS program facilitates early diagnosis of T2DM. METHODS: Students between the ages of 10-18 years old with age- and sex-specific body mass index (BMI) >97th percentile who attended SHS between the school years from 2005/06 to 2017/18 were recruited for UGS. Those tested positive for random urine glucose underwent diagnostic testing for T2DM according to ADA guidelines. Demographic data and investigatory results from UGS and HKCDR within the same time period were compared. RESULTS: A total of 216,526 students completed UGS in the said period; 415 (0.19 %) students were tested positive for urine glucose of which 121 students were diagnosed with T2DM. UGS picked up 23 % of the newly diagnosed T2DM cases. When compared to the HKCDR database, students diagnosed via UGS were significantly younger, less obese, and had fewer diabetic related complications. The negative predictive value of UGS is high and can effectively rule out T2DM. CONCLUSIONS: Urine glucose screening is an inexpensive and simple test that allows for early diagnosis of T2DM among obese school students. Other methods including POCT HbA1c can be explored to improve program effectiveness.