Postnatal renal tubule development: roles of tubular flow and flux.

PURPOSE OF REVIEW: Postnatal renal tubule development is critical to adult kidney function. Several postnatal changes regulate the differentiation and proliferation of renal tubular cells. Here, we review the literature and our efforts on thick ascending limb (TAL) development in Bartter syndrome (BS). RECENT FINDINGS: Glomerular filtrate quickly increases after birth, imposing fluid shear stress and circumferential stretch on immature renal tubules. Recent studies showed that kidney organoids under flow (superfusion) have better development of tubular structures and the expression of cilia and solute transporters. These effects are likely mediated by mechanosensors, such as cilia and the piezo1 channel. Improved renal oxygenation and sodium pump-dependent active transport can stimulate mitochondrial respiration and biogenesis. The functional coupling between transport and mitochondria ensures ATP supply for energy-demanding reactions in tubular cells, including cell cycle progression and proliferation. We recently discovered that postnatal renal medulla maturation and TAL elongation are impaired in Clc-k2-deficient BS mice. Primary cultured Clc-k2-deficient TAL cells have G1-S transition and proliferation delay. These developmental defects could be part of the early pathogenesis of BS and worsen the phenotype. SUMMARY: Understanding how tubular flow and transepithelial ion fluxes regulate renal tubule development may improve the treatment of congenital renal tubulopathies.

Icodextrin-induced acute generalized exanthematous pustulosis in a patient with peritoneal dialysis.

Icodextrin has been widely prescribed for peritoneal dialysis (PD) patients with inadequate ultrafiltration, but icodextrin induced acute generalized exanthematous pustulosis (AGEP) has been not well recognized in clinical practice. We described a young-aged female with IgA nephropathy and end stage kidney disease under continuous automated peritoneal dialysis. She developed skin erythema with exfoliation over the groin 7th day after initiation of icodextrin based PD dialysate. Initially, her scaling skin lesion with pinhead-sized pustules affected the bilateral inguinal folds, and then it extended to general trunk accompanied by pruritus. She was admitted because of deterioration of skin lesion on 14th day of icodextrin exposure. She was afebrile and physical examination was notable for widespread erythematous papules with pruritus extending over her groins and trunk. Pertinent laboratory examination showed leukocytosis of 18 970 cells/µL with neutrophile count of 17 642 cells/µL (92.3%), and c-reactive-protein: 3.39 mg/dL. Skin biopsy revealed multifocal sub corneal abscess with papillary dermal edema, and upper-dermal neutrophilia with perivascular accentuation, consistent with the diagnosis of AGEP. After discontinuation of PD, she underwent temporary high-flux haemodialysis with treatment of steroid and antihistamine. Her dermatologic lesion resolved without any skin sequalae completely within 4 days, and she underwent icodextrin-free peritoneal dialysis at 17th day. This case highlighted the fact that icodextrin-induced AGEP should be early recognized to avoid inappropriate management.

Inactivation of mitochondrial pyruvate carrier promotes NLRP3 inflammasome activation and gout development via metabolic reprogramming.

The nucleotide-binding and oligomerization domain, leucine-rich repeats, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in innate immunity and is involved in the pathogenesis of autoinflammatory diseases. Glycolysis regulates NLRP3 inflammasome activation in macrophages. However, how lactic acid fermentation and pyruvate oxidation controlled by the mitochondrial pyruvate carrier (MPC) affect NLRP3 inflammasome activation and autoinflammatory disease remains elusive. We found that the inactivation of MPC with genetic depletion or pharmacological inhibitors, MSDC-0160 or pioglitazone, increased NLRP3 inflammasome activation and IL-1ß secretion in macrophages. Glycolytic reprogramming induced by MPC inhibition skewed mitochondrial ATP-associated oxygen consumption into cytosolic lactate production, which enhanced NLRP3 inflammasome activation in response to monosodium urate (MSU) crystals. As pioglitazone is an insulin sens MSDC-itizer used for diabetes, its MPC inhibitory effect in diabetic individuals was investigated. The results showed that MPC inhibition exacerbated MSU-induced peritonitis in diabetic mice and increased the risk of gout in patients with diabetes. Altogether, we found that glycolysis controlled by MPC regulated NLRP3 inflammasome activation and gout development. Accordingly, prescriptions for medications targeting MPC should consider the increased risk of NLRP3-related autoinflammatory diseases.

Incorporating knowledge of disease-defining hub genes and regulatory network into a machine learning-based model for predicting treatment response in lupus nephritis after the first renal flare.

BACKGROUND: Identifying candidates responsive to treatment is important in lupus nephritis (LN) at the renal flare (RF) because an effective treatment can lower the risk of progression to end-stage kidney disease. However, machine learning (ML)-based models that address this issue are lacking. METHODS: Transcriptomic profiles based on DNA microarray data were extracted from the GSE32591 and GSE112943 datasets. Comprehensive bioinformatics analyses were performed to identify disease-defining genes (DDGs). Peripheral blood samples (GSE81622, GSE99967, and GSE72326) were used to evaluate the effect of DDGs. Single-sample gene set enrichment analysis (ssGSEA) scores of the DDGs were calculated and correlated with specific immunology genes listed in the nCounter panel. GSE60681 and GSE69438 were used to examine the ability of the DDGs to discriminate LN from other renal diseases. K-means clustering was used to obtain the separate gene sets. The clustering results were extended to data derived using the nCounter technique. The least absolute shrinkage and selection operator (LASSO) algorithm was used to identify genes with high predictive value for treatment response after the first RF in each cluster. LASSO models with tenfold validation were built in GSE200306 and assessed by receiver operating characteristic (ROC) analysis with area under curve (AUC). The models were validated by using an independent dataset (GSE113342). RESULTS: Forty-five hub genes specific to LN were identified. Eight optimal disease-defining clusters (DDCs) were identified in this study. Th1 and Th2 cell differentiation pathway was significantly enriched in DDC-6. LCK in DDC-6, whose expression positively correlated with various subsets of T cell infiltrations, was found to be differentially expressed between responders and non-responders and was ranked high in regulatory network analysis. Based on DDC-6, the prediction model had the best performance (AUC: 0.75; 95% confidence interval: 0.44-1 in the testing set) and high precision (0.83), recall (0.71), and F1 score (0.77) in the validation dataset. CONCLUSIONS: Our study demonstrates that incorporating knowledge of biological phenotypes into the ML model is feasible for evaluating treatment response after the first RF in LN. This knowledge-based incorporation improves the model's transparency and performance. In addition, LCK may serve as a biomarker for T-cell infiltration and a therapeutic target in LN.

Trichomonas infection in pregnant women: a nationwide cohort study.

Trichomoniasis is the most prevalent sexually transmitted infection worldwide, and is associated with adverse pregnancy outcomes. However, Trichomonas vaginalis (TV) has received little public health attention, and only limited data are available on prevalence of TV and other Trichomonas-associated syndromes in pregnant women. This study aimed to determine associations between pregnancy and incident trichomoniasis-related diseases. Data of pregnant women were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. The pregnant cohort included 113,781 women, and cases were randomly matched by age, and index year with those of non-pregnant women (n = 113,781). Risk of incident trichomoniasis-related diseases was also not significantly different between pregnant and non-pregnant women. However, after stratifying by age or level of care, the younger subgroup among pregnant women had a higher risk of incident trichomoniasis-related diseases than did the younger subgroup in non-pregnant women, while the elder subgroup among pregnant women had a lower risk of incident trichomoniasis-related diseases than did the same subgroup in non-pregnant women (all p < 0.05). The higher level of care (medical center) subgroup among pregnant women had a lower risk of incident trichomoniasis-related diseases than did the same subgroup in non-pregnant women. In conclusions, although pregnancy is not significantly associated with risk of trichomoniasis-related diseases, data of the present study support an enhanced high level of medical care for pregnant women, emphasizing the potential of high medical care in reduced incidence of trichomoniasis-related diseases. This may be an effective strategy for reducing various pregnancy complications associated with trichomoniasis-related diseases.

Serum uric acid is associated with incident metabolic syndrome independent of body shape index and body roundness index in healthy individuals.

BACKGROUND AND AIMS: Elevated serum uric acid (SUA) levels, body shape index (BSI) and body roundness index (BRI) were associated with incident metabolic syndrome (MetS). We aimed to investigate the relationship among the SUA level, BSI, and BRI on the incidence of MetS. METHODS AND RESULTS: We retrospectively included 6221 healthy individuals from annual health exams at our hospital between 2016/1/1 and 2016/12/31. We defined hyperuricemia as SUA levels greater than 7 mg/dl in men and 6 mg/dl in women and MetS according to the contemporary definition. The study cohort included 6221 healthy individuals with an overall incidence rate of MetS of 9.8%. Compared with the normouricemic group, the hyperuricemic group had a greater incidence of MetS (17.2% vs. 9.6%, P < 0.001). After full adjustment for confounders, the SUA level was significantly associated with incident MetS in addition to body mass index (BMI) (adjusted OR [aOR]: 1.161, 95% CI: 1.071-1.259, P < 0.001), BRI (aOR: 1.196, 95% CI: 1.104-1.296, P < 0.001), and BSI (aOR: 1.297, 95% CI: 1.200-1.403, P < 0.001). Regarding the anthropometric indices, BMI and BRI were independent predictors of incident MetS, but the BSI lost its significant association in multivariate logistic regression analyses. In sensitivity analyses, various thresholds of elevated SUA levels remained associated with incident MetS. CONCLUSION: We showed a dose-response effect of SUA on incident MetS independent of BMI, BRI and BSI in healthy individuals. Future studies can use SUA levels to stratify cardiometabolic risk in healthy individuals. CLINICAL TRIALS: ClinicalTrials.gov with the identification number NCT03473951.

Prognostic role of RECK in pathological outcome-dependent buccal mucosa squamous cell carcinoma.

BACKGROUND: Buccal mucosal squamous cell carcinoma (BMSCC) is an aggressive oral cancer. Moreover, reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a well-known tumor suppressor in many cancers. Our aim was to investigate the association of RECK expression with prognosis in BMSCC patients with different clinicopathological features. MATERIALS AND METHODS: The expression level of RECK was determined by immunohistochemistry using tissue microarrays containing specimens from 193 BMSCC patients. The association of RECK expression with outcomes in BMSCC patients stratified by different clinicopathological features was analyzed by Cox proportional hazards models. RESULTS: The low expression level of RECK was associated with shorter disease-specific survival, especially in patients with age >40 years, moderate or poor cell differentiation, advanced pathological stage, and history of postoperative radiotherapy. However, the low expression level of RECK was not associated with poor disease-free survival, except in BMSCC patients with age ≦40 years, advanced pathological stage and lymph node metastasis. Furthermore, RECK-knockdowned cells showed higher cell viability and abilities of invasion/migration, indicating that RECK might be a tumor suppressor for tumor progression in oral cancer. CONCLUSION: The low expression of RECK might be a potential prognostic biomarker for pathological outcome-dependent BMSCC patients.

Patient and health care system characteristics are associated with delayed treatment of tuberculosis cases in Taiwan.

BACKGROUND: The decline of the incidence rate of tuberculosis in Taiwan has been partly attributed to the launch of the directly observed therapy short course (DOTS) program in 2006, followed by the DOTS-Plus in 2007. However, with the phasing out of the specialized tuberculosis care system and the declining incidence, clinical workers in Taiwan might become less familiar with the presentation of tuberculosis. Complementing the patient-pathway analysis with health system delay estimates, the objective of this study is twofold: to estimate the alignment between patient care initiation and the availability of prompt diagnostic and treatment services, and to identify the risk factors of delayed tuberculosis treatment. METHODS: The study population included all Taiwanese patients with incident tuberculosis in 2013. We (1) identified 11,507 incident tuberculosis patients from the 2013 National TB Registry, and (2) linked 10,932 Taiwanese from the registry to the 2012-2013 National Health Insurance Research Database. We assessed patient's care-seeking pathways and associated the determinants of health system delay in a Cox model. RESULTS: The overall health system delay was 46 days. We found that 20.5 and 3.5% of 10,932 tuberculosis patients were diagnosed and treated respectively at the initial visit to seek care for TB-related symptoms. Risk factors related to the prolonged health system delay included female gender (adjusted HR = 0.921, 95% CI: 0.884, 0.960), age > =65 years (adjusted HR = 0.720, 95% CI: 0.692, 0.750), non-severe (chest X-ray without cavities) (adjusted HR =0.721, 95% CI 0.683-0.760), chronic respiratory diseases (adjusted HR = 0.544, 95% CI: 0.522, 0.566), living in long-term care facilities (adjusted HR = 0.580, 95% CI: 0.525,0.640), an initial visit at a primary care clinic (adjusted HR = 0.588, 95% CI: 0.565, 0.612), and living in southern Taiwan (adjusted HR = 0.887, 95% CI: 0.798, 0.987). CONCLUSIONS: The low access to TB diagnostic and treatment services at the initial visit and the prolonged health system delay indicate inefficiency in the health care system. Strengthening training of physicians at public hospitals and health workers at nursing homes might improve the efficiency and timeliness of tuberculosis diagnosis and treatment in Taiwan.

Health Care Visits as a Risk Factor for Tuberculosis in Taiwan: A Population-Based Case-Control Study.

OBJECTIVES: To assess whether health care visits of nontuberculous patients are a risk factor for contracting tuberculosis. METHODS: We conducted a case-control study nested within the cohort of 1 million individuals from the health insurance database in Taiwan between 2003 and 2010. We identified incident cases of tuberculosis through International Classification of Diseases, Ninth Revision (ICD-9) codes and prescription of antituberculosis drugs. We identified 4202 case participants and 16 808 control participants matched by age, gender, and date of diagnosis to estimate the association between frequency of health care visits and incidence of tuberculosis. RESULTS: Frequency of health care visits was associated with increased risk of tuberculosis in a dose-dependent manner after adjustment for other medical comorbidities (P for trend < .001). Compared with individuals with fewer than 5 visits per year, those with more than 30 had a 77% increase in tuberculosis risk (adjusted odds ratio = 1.77; 95% confidence interval [CI] = 1.60, 1.97). CONCLUSIONS: Frequent health care visits of nontuberculous patients appear to be a risk factor for contracting tuberculosis. PUBLIC HEALTH IMPLICATIONS: Efforts should focus on educating the general population to avoid unnecessary hospital visits, strengthening active case finding, and intensifying infection control in all health care settings.

Online platform for applying space-time scan statistics for prospectively detecting emerging hot spots of dengue fever.

BACKGROUND: Cases of dengue fever have increased in areas of Southeast Asia in recent years. Taiwan hit a record-high 42,856 cases in 2015, with the majority in southern Tainan and Kaohsiung Cities. Leveraging spatial statistics and geo-visualization techniques, we aim to design an online analytical tool for local public health workers to prospectively identify ongoing hot spots of dengue fever weekly at the village level. METHODS: A total of 57,516 confirmed cases of dengue fever in 2014 and 2015 were obtained from the Taiwan Centers for Disease Control (TCDC). Incorporating demographic information as covariates with cumulative cases (365 days) in a discrete Poisson model, we iteratively applied space-time scan statistics by SaTScan software to detect the currently active cluster of dengue fever (reported as relative risk) in each village of Tainan and Kaohsiung every week. A village with a relative risk >1 and p value <0.05 was identified as a dengue-epidemic area. Assuming an ongoing transmission might continuously spread for two consecutive weeks, we estimated the sensitivity and specificity for detecting outbreaks by comparing the scan-based classification (dengue-epidemic vs. dengue-free village) with the true cumulative case numbers from the TCDC's surveillance statistics. RESULTS: Among the 1648 villages in Tainan and Kaohsiung, the overall sensitivity for detecting outbreaks increases as case numbers grow in a total of 92 weekly simulations. The specificity for detecting outbreaks behaves inversely, compared to the sensitivity. On average, the mean sensitivity and specificity of 2-week hot spot detection were 0.615 and 0.891 respectively (p value <0.001) for the covariate adjustment model, as the maximum spatial and temporal windows were specified as 50% of the total population at risk and 28 days. Dengue-epidemic villages were visualized and explored in an interactive map. CONCLUSIONS: We designed an online analytical tool for front-line public health workers to prospectively detect ongoing dengue fever transmission on a weekly basis at the village level by using the routine surveillance data.

Spatial decision on allocating automated external defibrillators (AED) in communities by multi-criterion two-step floating catchment area (MC2SFCA).

BACKGROUND: The occurrence of out-of-hospital cardiac arrest (OHCA) is a critical life-threatening event which frequently warrants early defibrillation with an automated external defibrillator (AED). The optimization of allocating a limited number of AEDs in various types of communities is challenging. We aimed to propose a two-stage modeling framework including spatial accessibility evaluation and priority ranking to identify the highest gaps between demand and supply for allocating AEDs. METHODS: In this study, a total of 6135 OHCA patients were defined as demand, and the existing 476 publicly available AEDs locations and 51 emergency medical service (EMS) stations were defined as supply. To identify the demand for AEDs, Bayesian spatial analysis with the integrated nested Laplace approximation (INLA) method is applied to estimate the composite spatial risks from multiple factors. The population density, proportion of elderly people, and land use classifications are identified as risk factors. Then, the multi-criterion two-step floating catchment area (MC2SFCA) method is used to measure spatial accessibility of AEDs between the spatial risks and the supply of AEDs. Priority ranking is utilized for prioritizing deployment of AEDs among communities because of limited resources. RESULTS: Among 6135 OHCA patients, 56.85 % were older than 65 years old, and 79.04 % were in a residential area. The spatial distribution of OHCA incidents was found to be concentrated in the metropolitan area of Kaohsiung City, Taiwan. According to the posterior mean estimated by INLA, the spatial effects including population density and proportion of elderly people, and land use classifications are positively associated with the OHCA incidence. Utilizing the MC2SFCA for spatial accessibility, we found that supply of AEDs is less than demand in most areas, especially in rural areas. Under limited resources, we identify priority places for deploying AEDs based on transportation time to the nearest hospital and population size of the communities. CONCLUSION: The proposed method will be beneficial for optimizing resource allocation while considering multiple local risks. The optimized deployment of AEDs can broaden EMS coverage and minimize the problems of the disparity in urban areas and the deficiency in rural areas.

Reduction of global 5-hydroxymethylcytosine is a poor prognostic factor in breast cancer patients, especially for an ER/PR-negative subtype.

DNA methylation at the 5 position of cytosine (5 mC) is an epigenetic hallmark in cancer. The 5 mC can be converted to 5-hydroxymethylcytosine (5 hmC) through a ten-eleven-translocation (TET). We investigated the impact of 5 mC, 5 hmC, TET1, and TET2 on tumorigenesis and prognosis of breast cancer. Immunohistochemistry was used to assess the levels of 5 mC, 5 hmC, TET1, and TET2 in the corresponding tumor adjacent normal (n = 309), ductal carcinoma in situ (DCIS, n = 120), and invasive ductal carcinoma (IDC, n = 309) tissues for 309 breast ductal carcinoma patients. 5 mC, 5 hmC, TET1-n, and TET2-n were significantly decreased during DCIS and IDC progression. In IDC, the decrease of 5 hmC was correlated with the cytoplasmic mislocalization of TET1 (p < 0.001) as well as poor disease-specific survival (DSS) (adjusted hazard ratio [AHR] 1.95, p = 0.003) and disease-free survival (DFS) (AHR 1.91, p = 0.006). The combined decrease of 5 mC and 5 hmC was correlated with worse DSS (AHR 2.19, p = 0.008) and DFS (AHR 1.99, p = 0.036). Stratification analysis revealed that the low level of 5 mC was associated with poor DSS (AHR 1.89, p = 0.044) and DFS (AHR 2.02, p = 0.035) for the ER/PR-positive subtype. Conversely, the low level of 5 hmC was associated with worse DSS (AHR 2.77, p = 0.002) and DFS (AHR 2.69, p = 0.006) for the ER/PR-negative subtype. The decreases of 5 mC, 5 hmC, TET1-n, and TET2-n were biomarkers of tumor development. The global reduction of 5 hmC was a poor prognostic factor for IDC, especially for ER/PR-negative subtype.

Health system delay among patients with tuberculosis in Taiwan: 2003-2010.

BACKGROUND: Taiwan has integrated the previous vertical tuberculosis (TB) control system into the general health care system. With the phase out of the specialized TB care system and the declining TB incidence, it is likely that clinical workers become less familiar with the presentation of TB, resulting in delay in TB diagnosis and treatment. METHODS: We used the detailed information of health care visits in the Taiwan National Health Insurance database to analyze the temporal pattern of the health system delay (HSD) among 3,117 patients with TB between 2003 and 2010. RESULTS: The median HSD was 29 days (interquartile range 5-73 days), and the median delay increased from 26 days in 2003 to 33.5 days in 2008, thereafter slightly decreased to 32 days in 2010. Patient factors associated with a longer HSD included: aged 45-64 and ≧65 years (as compared to aged <30 years); females (as compared to males); an initial visit as an outpatient (as compared to an inpatient). Provider factors were an initial visit to a provider not specialized in TB (as compared to a TB-related provider), to a primary care clinic or to a medical center (as compared to a district hospital), and in Central region, Northern region, KaoPing region, Southern region and Taipei region (as compared to in Eastern region). Longer distances from the point of initial visit to that of treatment were associated with longer HSD. Patients who switched among different levels or different types of medical care services during their illness exhibited the longest HSD. CONCLUSIONS: In countries where the TB care systems are being restructured from a vertical to a horizontal system, it is critical to monitor HSD and be aware of its increase. The potential increase in the HSD from 2003 to 2008 observed in this study is concerning and the decline of HSD after 2008 might be attributed to the launch of contact investigation. Our results call for actions to improve the efficiency of TB diagnosis in the health care system and to increase the awareness of TB among physicians and the general public.

Usual source of care and the quality of primary care: a survey of patients in Guangdong province, China.

INTRODUCTION: Usual source of care (USC) refers to the provider or place a patient consults when sick or in need of medical advice. No studies have been conducted in China to compare the quality of primary care provided with or without USC. The purpose of this study was to fill this gap in the literature by examining the quality of primary care provided between those having a USC and those without. Results of the study would provide implications for policymakers in terms of improving primary care performance in China, and help guide patients in their health care seeking behaviors. METHODS: A cross-sectional survey with patients was conducted in Guangdong province of China, using the Chinese validated Primary Care Assessment Tool (PCAT). ANOVA was performed to compare the overall and ten domains of primary care quality for patients with and without USC. Multivariate analyses were used to assess the association between USC and quality of primary care attributes while controlling for sociodemographic and health care characteristics. RESULTS: The study added evidence that having a USC can provide higher quality of primary care to patients than those without a USC. Results of this study showed that the PCAT score associated with those having a USC was significantly higher than those not having a USC. Moreover, the study showed that having a usual provider of care was also independently and significantly associated with patients' satisfaction with care. CONCLUSIONS: This study added evidence that in China, patients with a USC reported higher quality of medical care experiences compared with those without a USC. The efforts to improve quality of care should include policies promoting USC.

Artificial intelligence-enabled electrocardiography contributes to hyperthyroidism detection and outcome prediction.

BACKGROUND: Hyperthyroidism is frequently under-recognized and leads to heart failure and mortality. Timely identification of high-risk patients is a prerequisite to effective antithyroid therapy. Since the heart is very sensitive to hyperthyroidism and its electrical signature can be demonstrated by electrocardiography, we developed an artificial intelligence model to detect hyperthyroidism by electrocardiography and examined its potential for outcome prediction. METHODS: The deep learning model was trained using a large dataset of 47,245 electrocardiograms from 33,246 patients at an academic medical center. Patients were included if electrocardiograms and measurements of serum thyroid-stimulating hormone were available that had been obtained within a three day period. Serum thyroid-stimulating hormone and free thyroxine were used to define overt and subclinical hyperthyroidism. We tested the model internally using 14,420 patients and externally using two additional test sets comprising 11,498 and 596 patients, respectively. RESULTS: The performance of the deep learning model achieves areas under the receiver operating characteristic curves (AUCs) of 0.725-0.761 for hyperthyroidism detection, AUCs of 0.867-0.876 for overt hyperthyroidism, and AUC of 0.631-0.701 for subclinical hyperthyroidism, superior to a traditional features-based machine learning model. Patients identified as hyperthyroidism-positive by the deep learning model have a significantly higher risk (1.97-2.94 fold) of all-cause mortality and new-onset heart failure compared to hyperthyroidism-negative patients. This cardiovascular disease stratification is particularly pronounced in subclinical hyperthyroidism, surpassing that observed in overt hyperthyroidism. CONCLUSIONS: An innovative algorithm effectively identifies overt and subclinical hyperthyroidism and contributes to cardiovascular risk assessment.

Hyperthyroidism occurs when the thyroid gland produces too much hormone and can cause various symptoms including faster heartbeat, weight loss, and nervousness. Diagnosis is often missed, which can lead to heart problems and even death. Measurements of the heart's electrical activity can be obtained using Electrocardiograms (ECGs). We made a computational model that can detect hyperthyroidism from ECGs. Our model was better able to identify people with hyperthyroidism than currently available methods, especially the more severe forms of the condition. If future work demonstrates our model is safe and accurate, it could potentially be used to detect hyperthyroidism sooner, enabling faster treatment and improved health of people with hyperthyroidism.

Pioglitazone use increases risk of Alzheimer's disease in patients with type 2 diabetes receiving insulin.

Pioglitazone is an insulin resistance inhibitor widely used as monotherapy or combined with metformin or insulin in treating type 2 diabetes mellitus (T2DM). This study further investigated the relationship between pioglitazone use and the risk of developing Alzheimer's disease (AD) in patients newly diagnosed with T2DM, and examined the potential impact of insulin use on this association. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Our data exhibited that the risk of developing AD in the pioglitazone group was 1.584-fold (aHR = 1.584, 95% CI 1.203-1.967, p < 0.05) higher than that in the non-pioglitazone controls. Compared to patients without both insulin and pioglitazone, higher cumulative risk of developing AD was found in patients receiving both insulin and pioglitazone (aHR = 2.004, 95% CI = 1.702-2.498), pioglitazone alone (aHR = 1.596, 95% CI = 1.398-1.803), and insulin alone (aHR = 1.365, 95% CI = 1.125-1.572), respectively (all p < 0.05). A similar observation also found in the evaluation the use of diabetic drugs with a cumulative defined daily dose (cDDD). No interaction between pioglitazone and major risk factors (comorbidities) of AD was observed. In conclusion, alternative drug therapies may be an effective strategy for reducing risk of developing AD in T2DM patients.

Acute kidney disease following COVID-19 vaccination: a single-center retrospective study.

Background: Rare cases of de novo or relapsed kidney diseases associated with vaccination against coronavirus disease 2019 (COVID-19) have been increasingly reported. The aim of this study was to report the incidence, etiologies, and outcomes of acute kidney disease (AKD) following COVID-19 vaccination. Methods: This retrospective study extracted cases from renal registry of a single medical center from 1 March 2021 to 30 April 2022, prior to the significant surge in cases of the Omicron variant of COVID-19 infection in Taiwan. Adult patients who developed AKD after COVID-19 vaccination were included. We utilized the Naranjo score as a causality assessment tool for adverse vaccination reactions and charts review by peer nephrologists to exclude other causes. The etiologies, characteristics, and outcomes of AKD were examined. Results: Twenty-seven patients (aged 23 to 80 years) with AKD were identified from 1,897 vaccines (estimated rate of 13.6 per 1000 patient-years within the renal registry). A majority (77.8%) of vaccine received messenger RNA-based regimens. Their median (IQR) Naranjo score was 8 (6-9) points, while 14 of them (51.9%) had a definite probability (Naranjo score ≥ 9). The etiologies of AKD included glomerular disease (n = 16) consisting of seven IgA nephropathy, four anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (AAN), three membranous glomerulonephritis, two minimal change diseases, and chronic kidney disease (CKD) with acute deterioration (n = 11). Extra-renal manifestations were found in four patients. Over a median (IQR) follow-up period of 42 (36.5-49.5) weeks, six patients progressed to end-stage kidney disease (ESKD). Conclusion: Besides glomerulonephritis (GN), the occurrence of AKD following COVID-19 vaccination may be more concerning in high-risk CKD patients receiving multiple doses. Patients with the development of de novo AAN, concurrent extra-renal manifestations, or pre-existing moderate to severe CKD may exhibit poorer kidney prognosis.

Lactic acidosis associated with standard dose linezolid in a kidney recipient with impaired renal function.

Severe lactic acidosis, a mitochondrial toxicity caused by the recommended standard dosage of linezolid (LZD), may occur in patients with impaired renal function. We describe an adult male who underwent kidney transplantation with stably impaired renal function, severe dyspnea, and abdominal discomfort. He received a standard oral dose of LZD (600 mg twice daily) and azithromycin for three weeks with a reduced immunosuppressant dose due to pulmonary non-tuberculosis mycobacterial infection. He was alert and afebrile, with a blood pressure of 140/60 mmHg. Pertinent laboratory data showed: pH 7.12, PaCO2 13.6 mmHg; HCO3- 4.3 mmol/L and serum lactate 18.4 mmol/L. His trough serum LZD concentration reached toxic levels (21.4 µg/mL). With hemodialysis, his clinical symptoms improved, with a decline in serum LZD (9.8µg/mL) and lactate (3.2 mmol/L). Chronic standard dose LZD in patients with impaired renal function can lead to life-threatening lactic acidosis, especially in coexisting conditions that reduce LZD metabolism.

Case report: Severe rhabdomyolysis and acute liver injury in a high-altitude mountain climber.

Concurrent severe rhabdomyolysis and acute liver damage are rarely reported in the setting of acute high-altitude illness (AHAI). We described a 53-year-old healthy mountain climber who experienced headache and dyspnea at the summit of Snow Mountain (Xueshan; 3,886 m above sea level) and presented to the emergency room with generalized malaise, diffuse muscle pain, and tea-colored urine. His consciousness was alert, and he had a blood pressure of 114/74 mmHg, heart rate of 66/min, and body temperature of 36.8°C. Myalgia of the bilateral lower limbs, diminished skin turgor, dry oral mucosa, and tea-colored urine were notable. Urinalysis showed positive occult blood without red blood cells. The most striking blood laboratory data included creatine kinase (CK) 33,765 IU/L, inappropriately high aspartate aminotransferase (AST) 2,882 IU/L and alanine aminotransferase (ALT) 2,259 IU/L (CK/AST ratio 11.7, CK/ALT ratio 14.9), creatinine 1.5 mg/dl, serum urea nitrogen (BUN) 26 mg/dl, total bilirubin 1.7 mg/dl, ammonia 147 µg/ml, lactate 2.5 mmol/L, and prothrombin time 17.8 s. The meticulous search for the underlying causes of acute liver injury was non-revealing. With volume repletion, mannitol use, and urine alkalization coupled with avoidance of nephrotoxic and hepatotoxic agents, his clinical features and laboratory abnormality completely resolved in 3 weeks. Despite rarity, severe rhabdomyolysis and/oracute liver injury as a potential life-threatening condition requiring urgent management may occur in high-altitude hypobaric hypoxia.