Search

Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

Background: We evaluated whether postpartum muscle mass affects the risk of type 2 diabetes mellitus (T2DM) in Korean women with gestational diabetes mellitus (GDM).Methods: A total of 305 women with GDM (mean age, 34.9 years) was prospectively evaluated for incident prediabetes and T2DM from 2 months after delivery and annually thereafter. Appendicular skeletal muscle mass (ASM) was assessed with bioelectrical impedance analysis at the initial postpartum visit, and ASM, either divided by body mass index (BMI) or squared height, and the absolute ASM were used as muscle mass indices. The risk of incident prediabetes and T2DM was assessed according to tertiles of these indices using a logistic regression model.Results: After a mean follow-up duration of 3.3 years, the highest ASM/BMI tertile group had a 61% lower risk of incident prediabetes and T2DM compared to the lowest tertile group, and this remained significant after we adjusted for covariates (adjusted odds ratio, 0.37; 95% confidence interval [CI], 0.15 to 0.92; P=0.032). Equivalent findings were observed in normal weight women (BMI 2), but this association was not significant for overweight women (BMI ≥23 kg/m2). Absolute ASM or ASM/height2 was not associated with the risk of postpartum T2DM.Conclusion: A higher muscle mass, as defined by the ASM/BMI index, was associated with a lower risk of postpartum prediabetes and T2DM in Korean women with GDM.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder caused by genetic or epigenetic alterations at two imprinting centers (ICs) in the 11p15.5 region. Delineation of the molecular defects is important for prognosis and predicting familial recurrence. We evaluated epigenetic alterations and potential epigenotype-phenotype correlations in Korean children with BWS.Forty children with BWS with proven genetic or epigenetic defects in the 11p15.5 region were included. The phenotype was scored using the BWS consensus scoring system. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), bisulfite pyrosequencing, a single-nucleotide polymorphism microarray, andPatients met the criteria for genetic testing, with a mean clinical score of 5.4±2.0. Methylation alterations were consistent between MS-MLPA and bisulfite pyrosequencing in all patients. Twenty-six patients (65.0%) had IC2 loss of methylation (IC2-LoM), 11 (27.5%) had paternal uniparental disomy (patUPD), and one (2.5%) had IC1 gain of methylation. Macroglossia and external ear anomalies were more common in IC2-LoM than in patUPD, and lateralized overgrowth was more common in patUPD than in IC2-LoM (allComprehensive molecular analysis of the 11p15.5 region revealed epigenotype-phenotype correlations in our BWS cohort. Bisulfite pyrosequencing can help clarify epigenotypes. Methylation levels were correlated with fetal growth and clinical severity in patients with BWS.

The differential benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) in cardiovascular or renal outcomes have not been fully investigated.Patients with diabetes prescribed SGLT2i or GLP1RA were retrospectively identified. Patients treated with antihyperglycemic medications other than SGLT2i or GLP1RA were used as a control group. Primary outcomes were composite ischemic events (acute coronary syndrome, coronary revascularization, and stroke) and a composite of heart failure and renal events (hospitalization for heart failure, renal death, initiation of renal replacement therapy, and renal admission).During a median 38.7 months of follow-up, the incidence of composite ischemic events tended to be lower in the GLP1RA group (annualized rate 0.82% per person-year) than in the other groups (1.68% per person-year in the SGLT2i group and 1.36% per person-year in the control group). The risk of a composite of heart failure and renal outcomes was significantly lower in the SGLT2i group than in the GLP1RA and control groups (0.86% per person-year, 2.33% per person-year, and 1.48% per person-year, respectively). The SGLT2i group had a slower decline in renal function over time compared to that in other groups.SGLT2i showed more benefits in heart failure and renal outcomes, whereas GLP1RA tended to have more favorable ischemic outcomes.

Leg length discrepancy (LLD) is a common problem that can cause long-term musculoskeletal problems. However, measuring LLD on radiography is time-consuming and labor intensive, despite being a simple task.To develop and evaluate a deep-learning algorithm for measurement of LLD on radiographs.In this Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study, radiographs were obtained to develop a deep-learning algorithm. The algorithm developed with two U-Net models measures LLD using the difference between the bilateral iliac crest heights. For performance evaluation of the algorithm, 300 different radiographs were collected and LLD was measured by two radiologists, the algorithm alone and the model-assisting method. Statistical analysis was performed to compare the measurement differences with the measurement results of an experienced radiologist considered as the ground truth. The time spent on each measurement was then compared.Of the 300 cases, the deep-learning model successfully delineated both iliac crests in 284. All human measurements, the deep-learning model and the model-assisting method, showed a significant correlation with ground truth measurements, while Pearson correlation coefficients and interclass correlations (ICCs) decreased in the order listed. (Pearson correlation coefficients ranged from 0.880 to 0.996 and ICCs ranged from 0.914 to 0.997.) The mean absolute errors of the human measurement, deep-learning-assisting model and deep-learning-alone model were 0.7 ± 0.6 mm, 1.1 ± 1.1 mm and 2.3 ± 5.2 mm, respectively. The reading time was 7 h and 12 min on average for human reading, while the deep-learning measurement took 7 min and 26 s. The radiologist took 74 min to complete measurements in the deep-learning mode.A deep-learning U-Net model measuring the iliac crest height difference was possible on teleroentgenograms in children. LLD measurements assisted by the deep-learning algorithm saved time and labor while producing comparable results with human measurements.

Conjunctival goblet cells (CGCs) are mucin-secreting cells in the eye and play essential roles for ocular surface homeostasis. Since various ocular surface pathologies are related to CGC dysfunction, CGC examination is important for the evaluation of ocular surface conditions. Recently we introduced moxifloxacin-based fluorescence microscopy (MBFM) for non-invasive CGC imaging. However, the imaging speed was up to 1 frame per second (fps) and needed to be improved for clinical applications. In this study, we developed a high-speed moxifloxacin-based, extended depth-of-field (EDOF) microscopy system that operates at a maximum imaging speed of 15 fps. The system used a deformable mirror for the high-speed axial sweeping of focal plane during single-frame acquisitions. The acquired images contained both in-focus and out-of-focus information, and deconvolution was used to filter the in-focus information. The system had a DOF of 800 [Formula: see text], field-of-view of 1.2 mm ×1.2 mm, and resolution of [Formula: see text]. Its performance was demonstrated by real-time, breathing-motion-insensitive CGC imaging of mouse and rabbit models, in vivo. High-speed EDOF microscopy has potentials for non-invasive, real-time CGC examinations of human subjects.

Pulmonary vein stump thrombosis (PVST) is uncommonly encountered postoperative in-situ thrombosis in the stump of pulmonary veins after lung resection. Data regarding the incidence and clinical behaviour of PVST are scarce. Thus, this study aims to investigate the incidence, clinical characteristics and outcome of PVST after lung resection in patients with lung cancer. Follow-up enhanced chest computed tomography (CT) scans acquired after the surgery were retrospectively reviewed to determine PVST presence for patients with lung cancer who underwent lung resection in two tertiary referral centres. Out of the 1885 patients with lung cancer who underwent lobectomy or more extensive lung resection, PVST was observed in 37 patients (2.0%) on their follow-up chest CT. Most stump thrombi were observed in the left superior pulmonary vein [35 (94.6%)] and in patients who underwent left upper lobectomy [34 (91.9%)]. At the last CT follow-up of each patient, 33 (89.2%) exhibited complete resolution, three partial resolution and one stabilization. Eleven (29.7%) patients received anticoagulant therapy after the diagnosis. The rate of complete PVST resolution did not differ significantly between the anticoagulation and nonanticoagulation groups. None of the PVST patients experienced systemic embolic events, regardless of anticoagulation. The PVST incidence diagnosed at routine chest CT follow-up following lung cancer surgery was 2%. PVST was characterized by a benign clinical course without progression and systemic embolization, regardless of anticoagulation. However, further studies are required to determine individualized therapeutic strategies, including anticoagulation.

BackgroundReported bacteraemia outcomes following inactive empirical antibiotics (as judged by in vitro testing) are conflicting, potentially reflecting heterogeneous effects of species, minimum inhibitory concentration (MIC) breakpoints defining resistance/susceptibility, and times to rescue therapy.MethodsWe investigated adult inpatients with Escherichia coli bacteraemia at Oxford University Hospitals, UK, from 04-February-2014 to 30-June-2021 receiving empirical amoxicillin-clavulanate with/without other antibiotics. We analysed 30-day all-cause mortality from index blood culture using Cox models by in vitro amoxicillin-clavulanate susceptibility (activity) using the EUCAST resistance breakpoint (>8/2mg/L), categorical MIC, and a higher resistance breakpoint (>32/2mg/L), adjusting for other antibiotic activity and multiple confounders including comorbidities, vital signs, and blood tests.Results1720 E. coli bacteraemias (1626 patients) were treated with empirical amoxicillin-clavulanate. 30-day mortality was 193/1400 (14%) [any active baseline therapy] and 52/320 (16%) [inactive baseline therapy] (p=0.17). With EUCAST breakpoints, there was no evidence that mortality differed for inactive vs. active amoxicillin-clavulanate (adjusted HR, aHR=1.27 [95%CI 0.83-1.93;p=0.28]), nor of an association with other antibiotic activity (p>0.18). Considering categorical amoxicillin-clavulanate MIC, MICs>32/2 were associated with mortality (aHR=1.85 vs. MIC=2/2 [0.99-3.73;p=0.054]). Using the higher resistance breakpoint, MICs>32/2 were independently associated with higher mortality (aHR=1.82 [1.07-3.10;p=0.027]), as were MICs>32/2 with active baseline aminoglycoside (aHR=2.34 [1.40-3.89;p=0.001), but not MICs>32/2 with active baseline non-aminoglycoside antibiotic(s) (aHR=0.87 [0.40-1.89;p=0.72).ConclusionsEUCAST-defined amoxicillin-clavulanate resistance was not associated with increased mortality, but a higher resistance breakpoint was. Additional active baseline non-aminoglycoside antibiotics prevented amoxicillin-clavulanate resistance-associated mortality, but active baseline aminoglycosides did not. Granular phenotyping and comparison with clinical outcomes may improve AMR breakpoints.SummaryIn patients with E. coli bacteraemia, high-level resistance to baseline empirical amoxicillin-clavulanate (minimum inhibitory concentration >32/2 mg/L) was associated with increased 30-day mortality, which was not compensated for by single-dose aminoglycosides.

Background: Optimal management of primary aldosteronism (PA) is crucial due to the increased risk of cardiovascular and cerebrovascular diseases. Adrenal venous sampling (AVS) is the gold standard method for determining subtype but is technically challenging and invasive. Some PA patients do not benefit clinically from surgery. We sought to develop an algorithm to improve decision- making before engaging in AVS and surgery in clinical practice.Methods: We conducted the ongoing Korean Primary Aldosteronism Study at two tertiary centers. Study A involved PA patients with successful catheterization and a unilateral nodule on computed tomography and aimed to predict unilateral aldosterone-producing adenoma (n=367). Study B involved similar patients who underwent adrenalectomy and aimed to predict postoperative outcome (n=330). In study A, we implemented important feature selection using the least absolute shrinkage and selection operator regression.Results: We developed a unilateral PA prediction model using logistic regression analysis: lowest serum potassium level ≤3.4 mEq/L, aldosterone-to-renin ratio ≥150, plasma aldosterone concentration ≥30 ng/mL, and body mass index

Background Although a number of studies have reported on the health effects of fine particulate matter (PM2.5) exposure, particularly in North American and European countries as well as China, the evidence about intermediate to high levels of PM2.5 exposures is still limited. We aimed to investigate the associations between long-term exposure to PM2.5 and risk of cardiopulmonary disease incidence in Taiwan with intermediate levels of PM2.5 exposure. Methods A cohort of Taiwanese adults, who participated in the 2001, 2005, 2009 and 2013 National Health Interview Surveys, was followed through 2016 to identify cardiopulmonary disease onset. Exposure to PM2.5 was estimated by incorporating a widespread monitoring network of air quality monitoring stations and microsensors. We used time-dependent Cox regression models to examine the associations between the PM2.5 exposures and health outcomes, adjusting for individual characteristics and ecological covariates. The natural cubic spline functions were used to explore the non-linear effects of the PM2.5 exposure. Results A total of 62 694 adults from 353 towns were enrolled. Each 10-μg/m3 increase in 5-year average exposure to PM2.5 was associated with a 4.8% increased risk of incident ischaemic heart disease (95% CI: -3.3, 13.6), 3.9% increased risk of incident stroke (95% CI: -2.9, 11.1), 6.7% increased risk of incident diabetes (95% CI: 1.1, 12.7), 15.7% increased risk of incident lung cancer (95% CI: -0.9, 35.1) and 11.5% increased risk of incident chronic obstructive pulmonary disease (95% CI: -0.8, 25.2). The concentration-response curve showed that there was no statistical evidence of non-linearity for most of the disease outcomes except for ischaemic heart disease (P for non-linearity = 0.014). Conclusions Long-term exposure to intermediate levels of ambient PM2.5 was associated with cardiopulmonary health outcomes. Our study adds value to future application and national burden of disease estimation in evaluating the health co-benefits from ambient air pollution reduction policy in Asian countries.

Steroid-resistant rejection (SRR) in liver transplant occurs in about 10% of T cell-mediated rejection; prognosis of SRR is known to be worse than steroid-sensitive rejection (SSR). Only a few studies describe treatment methods or features for SRR, and there is no clear consensus yet. Therefore, the purpose of this study is to describe the difference between SSR and SRR and to compare the effect of the SRR treatment method performed our institution.This study is a 10-year, retrospective cohort study at Seoul St Mary's Hospital; clinical data were collected from January 2008 to December 2017. Of 663 cases, 154 patients (23.3%) underwent steroid pulse therapy for rejection; we excluded 30 patients who did not undergo liver biopsy. A total of 124 patients (18.7%) with biopsy-proven rejection were analyzed for this study.Child-Turcotte-Pugh score, cold ischemia time, and cytomegalovirus (CMV) infection showed a statistically significant difference in 2 groups. Multivariate analysis was performed on risk factors of SRR at first rejection. CMV infection and total bilirubin at first rejection and numbers of rejection were significant results. Both overall survival and allograft survival rate of SSR are higher than SRR (P.001). Of second-line treatment patients, 13 patients (54.2%) recovered, and 11 patients (45.8%) failed to recover. Survival was the highest in patients using antithymocyte globulin and in patients with liver retransplant.When the first rejection in liver transplant occurs, patients with high bilirubin level ​​and previous CMV infections are more likely to have SRR, so if they do not respond to steroid pulse therapy for the first time, either using antithymocyte globulin or liver retransplant preparation should be considered.

Acute kidney injury (AKI) is a common complication in patients undergoing liver transplantation (LT) for end-stage liver disease (ESLD), and renal replacement therapy (RRT) is required in many cases. This study was performed to identify the prognostic factors for patients undergoing RRT owing to AKI before living donor liver transplantation (LDLT).From January 2010 to December 2018, LDLT was performed in 464 adult patients in our center. We reviewed 33 patients who underwent RRT before LDLT among 464 consecutive cases. Patients who continued to RRT after LDLT or who underwent subsequent kidney transplantation were considered to have not recovered from renal impairment.Among 33 patients, there were 23 patients in the recovery group and 10 patients in the nonrecovery group. The preoperative duration of RRT was shorter in the recovery group, but it was not statistically significant. In the nonrecovery group, diabetes mellitus was found to have a higher prevalence and ischemic time was longer. Other perioperative factors were not significantly different between the 2 groups. After LDLT, the peak total bilirubin level was higher, and the intensive care unit stay was longer in the nonrecovery group. The overall survival rate was higher in the recovery group.Liver transplant recipients who maintain RRT after LDLT have poor outcome. It is necessary to know the risk factors and manage them well, perioperatively.

Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that regulate gene expression. We investigated whether variants in BET genes are associated with survival outcomes for lung cancer. To do this, the associations between 77 variants in BET family genes and survival outcomes were analyzed in 773 non‐small‐cell lung cancer (NSCLC) patients who underwent surgery (349 and 424 patients in the discovery and validation cohorts, respectively). We found that six variants were significantly associated with overall survival (OS) in the discovery cohort, and one variant (rs2506711C>T) was replicated in the validation cohort. BRD3 rs2506711C>T is located in the repressed area and has a strong linkage disequilibrium with rs2427964C>T in the promoter region. BRD3 rs2427964C>T was significantly associated with worse OS in the discovery cohort, validation cohort, and combined analysis. In a luciferase assay, promoter activity in the BRD3 rs2427964 T allele was significantly higher than that in the BRD3 rs2427964 C allele, which selectively bound with the transcriptional repressor SIN3A. Knockdown of BRD3 with BRD3‐specific siRNA decreased the proliferation and migration of lung cancer cells while also increasing the rate of apoptosis. These results suggest that BRD3 rs2427964C>T increases BRD3 expression through increased promoter activity, which is associated with poor prognosis for lung cancer., In this study, we investigated the association of BET gene variants with survival of patients with non‐small‐cell lung cancer (NSCLC). We observed that the rs2427964C>T SNP in the BRD3 promoter region was associated with poorer survival outcome. BRD3 promoter activity was higher in rs2427964_T than in rs2427964_C, which selectively bound with the transcriptional repressor SIN3A. Additionally, BRD3 silencing decreased the proliferation and migration of NSCLC cells. Our data suggest that elevated BRD3 expression regulated by rs2427964C>T leads to reduced overall survival in patients with NSCLC.

In patients with leg length discrepancy (LLD) and consequent pelvic obliquity, either the longitudinal axis of the pelvis or a line perpendicular to the ground may be used as the longitudinal reference line for measuring the lateral center-edge angle (LCEA). We aimed to (1) systematically inspect which longitudinal reference line has been used for measuring the LCEA in previous studies; (2) evaluate the frequency of change in the radiographical classification of acetabular overcoverage or undercoverage per the longitudinal reference line; and (3) validate the trigonometric method, predicting the change in the LCEA according to the LLD.Studies investigating the LCEA published between January 1976 and July 2019 in the MEDLINE database were categorized according to the longitudinal reference line used. Further, in a retrospective analysis of 238 patients surgically treated for LLD, the LCEA was first measured on standing pelvic radiographs using the longitudinal axis of the pelvis (pLCEA) and measured again using a line perpendicular to the ground (gLCEA). Femoral head coverage was categorized as undercoverage, normal, or overcoverage based on the pLCEA and gLCEA. The theoretically calculated difference between the pLCEA and gLCEA (dLCEA) as determined using a trigonometric method was compared with the dLCEA measured on radiographs.Of 229 previous studies, 188 did not specify the longitudinal reference line. The number of patients who were diagnosed with acetabular overcoverage using the pLCEA and gLCEA was one and fourteen, respectively (P0.001). The number of patients who were diagnosed with acetabular undercoverage using the pLCEA and gLCEA was one and zero, respectively (P=1.000). There was no difference (P=0.433) between the theoretically calculated (9±5 degrees) and measured (9±5 degrees) dLCEAs.The definition of the longitudinal reference line should be clarified when measuring the LCEA. The trigonometric method can accurately predict the change in the LCEA according to LLD in concentric hips without proximal femoral and pelvic deformities.Level IV-diagnostic study.

Summary Objective The purpose of this study was to determine whether TAE negatively impacted perioperative outcomes in patients who underwent open surgery for pelvic trauma. Methods We retrospectively reviewed the medical records and radiographs of patients who had open surgery for an acute pelvic trauma between February 2014 and May 2017. The patients were classified into two groups: those who underwent TAE and those who did not. We evaluated preoperative demographics and perioperative outcomes between the two groups. Injury type-specific comparisons were also performed. Results A total of 136 patients (50 TAE and 86 non-TAE) were included in this study. There were significant differences in preoperative demographics including the type of injury, injury severity score, revised trauma score, surgical approach, initial blood pressure, and the amount of transfusion within 24 h between the two groups. However, no differences in perioperative outcomes were identified except for the amount of total transfusion. There were significant differences between the two groups in the injury type-specific comparisons, specifically in the amount of transfusion within 24 h in patients with pelvic ring injury and in the injury severity score in patients with acetabular fracture. However, there was no difference in perioperative outcomes between the groups for either injury type. Conclusion In the present study, we were unable to identify negative effects of TAE on perioperative outcomes. Therefore, when considering open surgery subsequent to TAE, there is no evidence of increased risk for negative perioperative outcomes, especially with respect to bone healing and deep infection.

Background/Aims: Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs.Methods: Patients with TPE and MPE with pleural f luid ADA levels ≥ 40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve.Results: A total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural f luid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40 to 56 IU/L (3 points), pleural CEA level ≥ 6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥ 6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965.Conclusions: A scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.

Introduction Patients with aspiration pneumonia (AP) exhibit higher mortality than those with non-AP. However, data regarding predictors of short-term prognosis in patients with community-acquired AP are limited. Methods Patients hospitalized with community-acquired pneumonia (CAP) were retrospectively classified into aspiration pneumonia (AP) and non-AP groups. The AP patients were further divided into nonsurvivors and survivors by 30-day mortality, and various clinical variables were compared between the groups. Results Of 1249 CAP patients, 254 (20.3%) were classified into the AP group, of whom 76 patients (29.9%) died within 30 days. CURB-65, pneumonia severity index (PSI), and Infectious Diseases Society of America/American Thoracic Society criteria for severe CAP (SCAP) showed only modest prognostic performance for the prediction of 30-day mortality (c-statistics, 0.635, 0.647, and 0.681, respectively). Along with the PSI and SCAP, Eastern Cooperative Oncology Group performance status (ECOG-PS) and blood biomarkers, including, N-terminal of prohormone brain natriuretic peptide (NT-proBNP) and albumin, were independent predictors of 30-day mortality. In models based on clinical prediction rules, including CURB-65, PSI, and SCAP, the addition of ECOG-PS further improved their c-statistics compared to the clinical prediction rules alone. In the four combinations based on SCAP, ECOG-PS, and two blood biomarkers (NT-proBNP and albumin), the c-statistics further increased to reach approximately 0.8. Conclusions CURB-65, PSI, and SCAP exhibited only modest discriminatory power in predicting the 30-day mortality of patients with community-acquired AP. The addition of performance status and blood biomarkers, including NT-proBNP and albumin, further increased prognostic performance, showing good predictive accuracy in the SCAP-based model.

ObjectivePatients with ulcerative colitis (UC) diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN: high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in patients with UC with LGD and create a visual web tool to effectively communicate the risk.DesignIn our retrospective multicentre validated cohort study, adult patients with UC with an index diagnosis of LGD, identified from four UK centres between 2001 and 2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from three external centres (n=198). The validated model was embedded in a web tool to calculate patient-specific risk.ResultsFour clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD >1 cm (HR 2.7; 95% CI 1.2 to 5.9), unresectable or incomplete endoscopic resection (HR 3.4; 95% CI 1.6 to 7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR 3.1; 95% CI 1.5 to 6.7) and multifocality (HR 2.9; 95% CI 1.3 to 6.2). In the validation cohort, this four-variable model accurately predicted future AN cases with overall calibration Observed/Expected=1.01 (95% CI 0.64 to 1.52), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up.ConclusionMulticohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator (www.UC-CaRE.uk) can support treatment decision-making.

Background Ultrasound is commonly used for evaluating rotator cuff tears. However, little training in ultrasound imaging is provided during orthopedic residents’ training period. Therefore, we performed this study to determine how many ultrasound scans are required for orthopedic residents to be competent and self-confident in the diagnosis of supraspinatus tendon tears and to investigate whether senior residents outperformed junior residents. Methods We studied two third-year residents who had no previous experience of shoulder ultrasound and evaluated their ability to detect rotator cuff pathologies. Their learning curves were plotted using a cumulative summation analysis with a 20% acceptable failure rate compared to arthroscopic findings. Downward, upward, and horizontal cumulative summation trends indicated incompetence, exceptional competence, and competence, respectively. The diagnostic accuracy of third-year residents was compared with that of second-year residents and the number of cases required to gain self-confidence was evaluated. Results Cumulative summation analysis showed that after 26–28 scans, residents achieved the competence to correctly diagnose supraspinatus tears: an upward trend was observed from the beginning for full-thickness tears and a downward trend was observed for partial-thickness tears. Sensitivity and specificity were 0.95 and 0.79, respectively, for third-year residents and 0.91 and 0.58, respectively, for second-year residents. Residents reported self-confidence after 30 ultrasound scans for the detection of rotator cuff tears. Conclusions The number of scans that novices needed to be competent for detecting rotator cuff tears was approximately 30 cases, and the diagnostic accuracy of third-year residents was significantly higher than that of second-year residents.

Although previous studies have shown that aerobic and resistance exercise increase high-density lipoprotein cholesterol (HDL-C) levels, the optimal type of exercise has not been determined. Therefore, the purpose of this study was to investigate the association of jogging (a type of aerobic exercise) and weight training (a type of resistance exercise) with HDL-C levels in Taiwanese adults.The data used in this cross-sectional study were obtained from the Taiwan Biobank (TWB), which is a national health resource that contains the genetic information of Taiwanese volunteers aged 30-70 years. A total of 75,635 subjects (47,881 women and 27,754 men) were included in this study. The subjects were divided into four groups: jogging (Compared with no exercise, jogging, weight training, and mixed exercise were all associated with higher HDL-C levels (β = 2.5470, 2.6249, and 3.2117, respectively). As seen, the β value was highest for the mixed exercise group, followed by weight training and then jogging (In the current study, jogging and weight training were individually associated with higher levels of HDL-C. Engaging in both activities was associated with much higher levels of HDL-C. Our findings suggest that regular jogging and weight training might play an important role in increasing HDL-C levels.

Background and Objectives: Health-related physical fitness reduces the risk of chronic disease, promotes quality of life, and has enormous economic benefits considering the global health care costs resulting from obesity. However, relatively limited information is available regarding the dose–response relationship between scientific physical fitness and obesity risk. This study aimed to determine the associations of scientific physical fitness with body mass index (BMI) distribution and overweight/obesity risk among adults aged 23–64 years in Taiwan. Materials and Methods: We conducted a cross-sectional study and reviewed data derived from the Scientific Physical Fitness Testing Program, Sports Administration, Ministry of Education, Taiwan. Responses from 16,939 participants from the database (7761 men and 9178 women, aged 23–64 years) were collected in this study. Each participant completed a series of scientific physical fitness measurements, including cardiorespiratory fitness (3 min progressive knee-up and step [3MPKS] test), muscular fitness (hand grip strength), and flexibility (sit-and-reach test). Anthropometric measurements included body height, weight, and BMI. The quartiles of scientific physical fitness results were identified as the dependent variable in the multiple linear and multiple logistic regression analysis to determine the associations of the scientific physical fitness measurements with BMI distribution and overweight/obesity risk, as well as the dose–response relationship. Results: The 3MPKS test was significantly associated with BMI (quartile 1 (Q1): β = 1.900; quartile 2 (Q2): β = 1.594; quartile 3 (Q3): β = 1.079 for men, and Q1: β = 1.454; Q2: β = 0.882; Q3: β = 0.555 for women), overweight (Q1: odds ratio (OR) = 2.117; Q2: OR = 2.056; Q3: OR = 2.063 for men, and Q1: OR = 3.036; Q2: OR = 2.542; Q3: OR = 1.959 for women), and obesity (Q1: OR = 6.530; Q2: OR = 5.747; Q3: OR = 3.557 for men, and Q1: OR = 3.238; Q2: OR = 1.431 for women) risk compared with quartile 4 (Q4) as the reference group with a dose–response relationship. In addition, relative hand grip strength was significantly associated with BMI (Q2: β = −0.922; Q3: β = −1.865; Q4: β = −3.108 for men, and Q2: β = −1.309; Q3: β = −2.161; Q4: β = −2.759 for women), overweight (Q2: OR = 0.806; Q3: OR = 0.697; Q4: OR = 0.278 for men, and Q2: OR = 0.667; Q3: OR = 0.398; Q4: OR = 0.228 for women), and obesity (Q1: OR = 0.528; Q2: OR = 0.206; Q3: OR = 0.049 for men, and Q1: OR = 0.351; Q2: OR = 0.129; Q3: OR = 0.051 for women) risk compared with Q1 as the reference group with a dose–response relationship. Conclusions: Higher levels of performance of the 3MPKS and relative grip strength tests were associated with lower BMI and overweight/obesity risk in both sexes. However, the sit-and-reach test was only partially related to BMI and overweight/obesity risk in both sexes. Cardiorespiratory fitness and muscular fitness were effective predictors of BMI distribution and overweight/obesity risk in Taiwanese adults.

Background: Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids.Methods: The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors.Results: The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT.Conclusion: The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

To provide real-world experiences of treating polypoidal choroidal vasculopathy (PCV) patients with photodynamic therapy (PDT) plus intravitreal injection of ranibizumab or intravitreal injection of aflibercept alone. Retrospective chart review of patients with PCV in a single tertiary referral center in Taiwan. Chart review of PCV patients treated with PDT and injection of ranibizumab or injection of aflibercept. A total of 101 eyes of 101 patients (38 females and 63 males) were reviewed. Of those, 48 and 53 eyes received primary/adjunctive PDT along with injections of ranibizumab or intravitreal injections of aflibercept only, respectively. Initial visual acuity (VA) and central subfield choroidal thickness were similar between the two groups (p > 0.05). In addition, changes in VA at 3, 6, and 12 months post treatment were similar. The central retinal thickness decreased with either treatment (p p > 0.05). In the subgroup analysis of pachychoroid and non-pachychoroid patients, better initial VA and post-treatment VA at 3 months and 6 months was noted in the latter group of patients treated with anti-vascular endothelial growth factor monotherapy (p

BackgroundHemihyperplasia and hemihypoplasia result in leg length discrepancy (LLD) by causing skeletal asymmetry. Beckwith–Wiedemann syndrome (BWS) and Silver–Russell syndrome (SRS) are opposite growth-affecting disorders caused by opposite epigenetic alterations at the same chromosomal locus, 11p15, to induce hemihyperplasia and hemihypoplasia, respectively. Because of their somatic mosaicism, BWS and SRS show a wide spectrum of clinical phenotypes. We evaluated the underlying epigenetic alterations and potential epigenotype-phenotype correlations, focusing on LLD, in a group of individuals with isolated hemihyperplasia/hemihypoplasia.ResultsWe prospectively collected paired blood-tissue samples from 30 patients with isolated hemihyperplasia/hemihypoplasia who underwent surgery for LLD. Methylation-specific multiplex-ligation-dependent probe amplification assay (MS-MLPA) and bisulfite pyrosequencing for differentially methylated regions 1 and 2 (DMR1 and DMR2) on chromosome 11p15 were performed using the patient samples. Samples from patients showing no abnormalities in MS-MLPA or bisulfite pyrosequencing were analyzed by single nucleotide polymorphism (SNP) microarray andCDKN1CSanger sequencing. We introduced a metric named as the methylation difference, defined as the difference in DNA methylation levels between DMR1 and DMR2. The correlation between the methylation difference and the predicted LLD at skeletal maturity, calculated using a multiplier method, was evaluated. Predicted LLD was standardized for stature. Ten patients (33%) showed epigenetic alterations in MS-MLPA and bisulfite pyrosequencing. Of these, six and four patients had epigenetic alterations related to BWS and SRS, respectively. The clinical diagnosis of hemihyperplasia/hemihypoplasia was not compatible with the epigenetic alterations in four of these ten patients. No patients showed abnormalities in SNP array or theirCDKN1Csequences. The standardized predicted LLD was moderately correlated with the methylation difference using fat tissue (r = 0.53;p = 0.002) and skin tissue (r = 0.50;p = 0.005) in all patients.ConclusionsIsolated hemihyperplasia and hemihypoplasia can occur as a spectrum of BWS and SRS. Although the accurate differentiation between isolated hemihyperplasia and isolated hemihypoplasia is important in tumor surveillance planning, it is often difficult to clinically differentiate these two diseases without epigenetic tests. Epigenetic tests may play a role in the prediction of LLD, which would aid in treatment planning.

Background: Heart rate (HR) monitored by a wearable device (WD) has demonstrated its clinical feasibility for thyrotoxicosis subjects. However, the association of HR monitored by wearables with hypothyroidism has not been examined. We assessed the association between serum thyroid hormone concentration and three WD-HR parameters in hypothyroid subjects.Methods: Forty-four subjects scheduled for radioactive iodine therapy (RAI Tx) after thyroid cancer surgery were included. Thirty subjects were prepared for RAI Tx by thyroid hormone withdrawal (hypothyroidism group) and 14 subjects by recombinant human thyrotropin (control group). Three WD-HR parameters were calculated from the HR data collected during rest, during sleep, and from 2:00 AM to 6:00 AM, respectively. We analyzed the changes in conventionally measured resting HR (On-site rHR) and WDHR parameters relative to thyroid hormone levels.Results: Serum free thyroxine (T4) levels, On-site rHR, and WD-HR parameters were lower in the hypothyroid group than in the control group at the time of RAI Tx. WD-HR parameters also reflected minute changes in free T4 levels. A decrease in On-site rHR and WD-HR parameters by one standard deviation (On-site rHR, approximately 12 bpm; WD-HR parameters, approximately 8 bpm) was associated with a 0.2 ng/dL decrease in free T4 levels (P

BACKGROUND: Doctors with various specializations and experience order brain computed tomography (CT) to rule out intracranial hemorrhage (ICH). Advanced artificial intelligence (AI) can discriminate subtypes of ICH with high accuracy. OBJECTIVE: The purpose of this study was to investigate the clinical usefulness of AI in ICH detection for doctors across a variety of specialties and backgrounds. METHODS: A total of 5702 patients’ brain CTs were used to develop a cascaded deep-learning-based automated segmentation algorithm (CDLA). A total of 38 doctors were recruited for testing and categorized into nine groups. Diagnostic time and accuracy were evaluated for doctors with and without assistance from the CDLA. RESULTS: The CDLA in the validation set for differential diagnoses among a negative finding and five subtypes of ICH revealed an AUC of 0.966 (95% CI, 0.955–0.977). Specific doctor groups, such as interns, internal medicine, pediatrics, and emergency junior residents, showed significant improvement with assistance from the CDLA (p= 0.029). However, the CDLA did not show a reduction in the mean diagnostic time. CONCLUSIONS: Even though the CDLA may not reduce diagnostic time for ICH detection, unlike our expectation, it can play a role in improving diagnostic accuracy in specific doctor groups.

This study highlights the clinical features and treatment response of polypoidal choroidal vasculopathy (PCV) among three different branching vascular network (BVN) morphologies in optical coherence tomography angiography (OCTA), and further correlates the BVN features with those under fluorescent angiography (FA) and indocyanine green angiography (ICGA). In total, we reviewed 70 eyes with PCV followed up for > 12 months. OCTA, ICGA and FA images were obtained at baseline and post-treatments. BVN was assessed using OCTA and divided into three types by a previously described BVN classification: type 1 (trunk), type 2 (glomeruli), and type 3 (stick). At baseline, type 1 BVN had the poorest vision and thinnest subfoveal choroidal thickness (SFCT), whereas type 3 had the best vision and thickest SFCT. The aforementioned trend sustained after treatments. Each BVN morphology in OCTA showed typical features in FA + ICGA and encompassed significant correlation (p = 0.004). In conclusion, OCTA is an innovative imaging tool for the detection and classification of BVN in PCV. Furthermore, OCTA has advantages of being noninvasive and free of systemic toxicities. The BVN can be divided into three types based on morphological characteristics in OCTA, which play crucial roles in clinical presentations and treatment outcomes.

Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.

Background and purpose Previous studies have identified that the reverse shock index multiplied by the Glasgow Coma Scale score (rSIG) is a good predictor of mortality in trauma patients. However, it is unknown if rSIG has utility as a predictor for massive transfusion (MT) in trauma patients. The present study evaluated the ability of rSIG to predict MT in trauma patients. Methods This was a retrospective, observational study performed at a level 1 trauma center. Consecutive patients who presented to the trauma center emergency department between January 2016 and December 2018 were included. The predictive ability of rSIG for MT was assessed as our primary outcome measure. Our secondary outcome measures were the predictive ability of rSIG for coagulopathy, in-hospital mortality, and 24-h mortality. We compared the prognostic performance of rSIG with the shock index, age shock index, and quick Sequential Organ Failure Assessment. Results In total, 1627 patients were included and 117 (7.2%) patients received MT. rSIG showed the highest area under the receiver operating characteristic (AUROC) curve (0.842; 95% confidence interval [CI], 0.806–-0.878) for predicting MT. rSIG also showed the highest AUROC for predicting coagulopathy (0.769; 95% CI, 0.728–0.809), in-hospital mortality (AUROC 0.812; 95% CI, 0.772–0.852), and 24-h mortality (AUROC 0.826; 95% CI, 0.789–0.864). The sensitivity of rSIG for MT was 0.79, and the specificity of rSIG for MT was 0.77. All tools had a high negative predictive value and low positive predictive value. Conclusion rSIG is a useful, rapid, and accurate predictor for MT, coagulopathy, in-hospital mortality, and 24- h mortality in trauma patients.

The association between air pollutants and Meniere’s disease has not been explored. The present study investigated the relationship between meteorological factors and air pollutants on Meniere’s disease. Participants, aged ≥ 40 years, of the Korean National Health Insurance Service-Health Screening Cohort were included in this study. The 7725 patients with Meniere’s disease were matched with 30,900 control participants. The moving average meteorological and air pollution data of the previous 7 days, 1 month, 3 months, and 6 months before the onset of Meniere’s disease were compared between the Meniere’s disease and control groups using conditional logistic regression analyses. Additional analyses were conducted according to age, sex, income, and residential area. Temperature range; ambient atmospheric pressure; sunshine duration; and levels of SO2, NO2, O3, CO, and PM10 for 1 month and 6 months were associated with Meniere’s disease. Adjusted ORs (odds ratios with 95% confidence interval [CI]) for 1 and 6 months of O3 concentration were 1.29 (95% CI 1.23–1.35) and 1.31 (95% CI 1.22–1.42), respectively; that for the 1 and 6 months of CO concentration were 3.34 (95% CI 2.39–4.68) and 4.19 (95% CI 2.79–6.30), respectively. Subgroup analyses indicated a steady relationship of O3 and CO concentrations with Meniere’s disease. Meteorological factors and air pollutants were associated with the rate of Meniere’s disease. In particular, CO and O3 concentrations were positively related to the occurrence of Meniere’s disease.

To investigate the structure–function correlation analysed by full-field electroretinography (ffERG) and optical coherence tomography (OCT) in typical and pericentral subtypes of retinitis pigmentosa (RP). A retrospective, cross-sectional, observational study of right eyes was conducted. The primary analysis used ffERG data to compare the RP subtypes. The subgroup analysis was used to correlate the structure, analysed by OCT, and function, determined by ffERG. Linear regressions explored the relationship between best-corrected visual acuity (BCVA) and multiple parameters. A total of 188 eyes were included. Amplitudes of responses of rod, rod-cone, cone, and 30 Hz flicker of typical type were lower than those of pericentral and other types. In the subgroup analysis, 41 and 21 eyes of the typical and pericentral types were studied, respectively. The correlation between the estimated preserved photoreceptor area and all ffERG amplitude parameters were significant in the typical type, but not in pericentral type. Old age, decreased intact ellipsoid zone length, typical type, and thin central retinal thickness were negatively correlated with BCVA. Typical type RP developed more extensive degeneration and poorer BCVA compared to others. Strong structure–function correlation was found in typical type while not in pericentral type. OCT may be a useful tool for monitoring RP status in typical type, providing useful parameters for the prediction of BCVA.

Objectives: To assess whether virtual non-contrast (VNC) computed tomography (CT) images acquired from dual-energy CT (DECT) have sufficient image quality to replace true non-contrast (TNC) CT images in CT angiography (CTAG). Methods: This study enrolled 63 consecutive patients who underwent a CTAG that included a single-energy non-contrast scan, followed by a post-contrast DECT scan. Comparison of attenuation and noise between TNC and VNC images was made by drawing circular regions of interest (ROI) on a picture archiving and communication system (PACS) workstation within the aortic lumen at the levels of the renal arteries, the aortic bifurcation and right femoral artery. Mean attenuation and image noise (one standard deviation) were registered in Hounsfield units (HU). The VNC images were subjectively evaluated for artifacts such as subtraction of calcifications or architectural distortion based on TNC image as a standard of reference. Results: Most attenuations of the VNCs were higher than TNC, except right femoral artery of reader 2. Most image noises of TNC were higher than VNC, except abdominal aorta in reader 1. In qualitative image analysis, mean scores of VNC according to the 5-point scale were 3.68 and 3.63 (reader 1 and reader 2, respectively) which mean good to excellent to diagnose. Conclusion: HUs and VNC image noises are different from TNC images in CTAG. VNC images have sufficient image quality to replace TNC images in the diagnosis of calcific lesions. Advances in knowledge: VNC images acquired from DECT have image quality adequate to replace TNC images in the diagnosis of the calcific lesion on the CTAG. VNC images based on DECT can avoid excessive and unnecessary patient exposure to radiation during CTAG.

A high rate of Meniere’s disease (MD) in patients with osteoporosis has been suggested. This research intended to estimate the bidirectional association of MD with osteoporosis. The ≥40-year-old population in the Korean National Health Insurance Service-Health Screening Cohort 2002–2019 was examined. In study I, 9529 patients with MD and 38,116 control I participants were analyzed for a previous history of osteoporosis. In study II, 65,858 patients with osteoporosis and 65,858 control II participants were analyzed for a previous history of MD. Stratified Cox proportional hazard models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MD for osteoporosis in study I and of osteoporosis for MD in study II. The rate of a prior history of osteoporosis was 13.3% for the MD group and 11.3% for the control I group. The patients with MD had a 1.12 times higher HR for previous osteoporosis (95% CI = 1.04–1.20). In study II, the rate or a prior history of MD was 3.7% for patients with osteoporosis and 2.0% for the control II group. The patients with osteoporosis had a 1.50 times higher HR for previous MD (95% CI = 1.40–1.61). Most subgroups according to age, sex, and comorbid conditions demonstrated consistent bidirectional associations between MD and osteoporosis. Adult patients with MD had a greater risk of osteoporosis. In addition, adult patients with osteoporosis also showed a higher risk of MD.

Differential leukocyte counts of pleural fluid are routinely recommended for the early diagnosis and management of exudative pleural effusions. Rapid automated cellular analysis agrees strongly with standard manual microscopic counts and has become a reality in many clinical laboratories. However, discordant results sometimes observed between automated and manual analyses raise concern about using automated analysis to aid prompt differential diagnosis. This study aimed to evaluate the real-world disagreement between automated and manual leukocyte analyses in exudative pleural effusions and to investigate whether the discordant results occur in specific cellular ranges or randomly. We conducted a retrospective study of patients who were diagnosed with parapneumonic pleural effusions (PPE), tuberculous pleural effusions (TPE), and malignant pleural effusions (MPE) between September 2018 and December 2020. Differential and predominant leukocyte counts were performed using an automated XN-350 analyzer with a two-part differential count consisting of polymorphonuclear (PMN) and mononuclear (MN) leukocytes and a manual method with Wright-stained cytospin slides. We compared the two methods on cases of 109 PPEs, 50 TPEs, and 116 MPEs. Although the overall correlation between the two methods for differential leukocyte counts was excellent, there were etiologic variations; MPEs showed a lower correlation compared to PPEs and TPEs. Automated-PMN predominance almost corresponded to manual cytospin-neutrophilic predominance. In contrast, ~10% of the automated-MN predominance did not correspond with the cytospin-lymphocytic predominance. These discrepancies occurred most in the automated-MN% range of 51% to 60%, followed by 61% to 70%. The PMN% range ≥50% and30% on the automated analysis reliably corresponds to the neutrophilic and lymphocytic predominance, respectively. However, the MN% range of 51% to 70% may not coincide with lymphocytic predominance on manual cytospin analysis. This range leaves the potential cause of exudative pleural effusions open.

Urinary crystals are the most diverse forms of urine sediments. Reference images for typical urinary crystals are common, however, but images for interpreting atypical urinary crystals are very rare. The authors reviewed various forms and solubility tests of urine crystals to interpret atypical crystals found in clinical specimens.We reviewed textbooks on urinary crystals and articles published in PubMed. Some atypical crystals were confirmed using a solubility test.The classification, shape, chemical structure, and solubility of the crystals were summarized. In the solubility test, some crystals showed different results; therefore, a new solubility test was proposed based on the literature review. We presented various types of calcium oxalates.These review articles will be helpful in the examination of atypical crystals found in clinical specimens. The solubility test requires additional studies to discriminate the inconsistent results between the authors.

Background:Arthroscopic superior capsular reconstruction (ASCR) is a method for treating irreparable chronic rotator cuff tears. However, the extent to which ASCR can be performed with regard to the patient’s age has yet to be determined.Purpose:To compare the surgical outcomes of ASCR for the treatment of irreparable rotator cuff tears (IRCTs) in patients aged Study Design:Cohort study; Level of evidence, 3.Methods:Of 105 patients with IRCTs who underwent ASCR between March 2013 and June 2020, 73 patients were enrolled in this study based on the selection criteria. Polypropylene mesh augmentation to the graft was used in 18 of 36 patients in the younger adults group (age, Results:The mean age of the patients was 59.2 ± 3.8 years in the younger adults group and 70.5 ± 4.1 years in the older adults group. Both groups showed improvement based on the clinical and radiological outcomes at the final follow-up. The mean American Shoulder and Elbow Surgeons scores improved from 52.3 ± 15.4 to 77.3 ± 13.5 in the younger adults group ( P < .001) and from 45.7 ± 16.1 to 76.6 ± 11.4 in the older adults group ( P < .001). The mean visual analog scale for pain scores improved from 5.5 ± 1.2 to 2.1 ± 0.9 in the younger adults group ( P < .001) and from 5.5 ± 1.4 to 2.1 ± 1.2 in the older adults group ( P < .001). The graft healing rate was significantly higher in the younger adults group (81%) than in the older adults group (65%) ( P = .049). Subgroup analysis showed that after mesh augmentation, the healing rate in the younger adults group (84%) was similar to that in the older adults group (85%) ( P = .299).Conclusion:ASCR resulted in a favorable surgical outcome for both younger and older adult patients with IRCT. The younger patients had lower graft failure rates and superior surgical outcomes. In older patients, ASCR using polypropylene mesh augmentation may reduce graft failure and result in surgical outcomes similar to those in younger patients.

Diabetes, a chronic metabolic disorder, is characterized by persistent hyperglycemia. This study aimed to evaluate the hypoglycemic and antioxidant activities of lactic acid bacteria strains isolated from humans and food products and investigate the probiotic properties of the selected four strains. The hypoglycemic activity of the isolated strains was examined by evaluating the α-glucosidase and α-amylase inhibitory activities. The antioxidant activity was measured using the DPPH, ABTS, and FRAP assays. Four strains (Lactiplantibacillus plantarum MG4229, MG4296, MG5025, and Lacticaseibacillus paracasei MG5012) exhibited potent α-glucosidase inhibitory (>75%) and α-amylase inhibitory (>85%) activities, which were comparable to those of acarbose (>50%; 1000 μg/mL). Similarly, the radical scavenging and antioxidant activities of the four strains were comparable to those of ascorbic acid (50 μg/mL). Additionally, the probiotic properties of the four selected strains were examined based on acid and bile salt tolerance, auto-aggregation ability, and antibiotic resistance. The four strains were resistant to pH 2 (>50% of survivability) and 0.5% bile salt (>80% of survivability). Therefore, we suggest that the selected strains with hypoglycemic, antioxidant, probiotic properties can potentially prevent diabetes. Supplementary Information The online version contains supplementary material available at 10.1007/s00284-021-02588-5.

This study aimed to investigate the association of previous stain use with hearing impairment in an adult population. Data from the ≥ 40-year-old population in the Korean National Health Insurance Service Health Screening Cohort were used. The hearing impairment group was classified based on the national registry of hearing-impaired persons. Control participants were randomly selected and matched for age, sex, income, and region of residence. The number of days of statin prescription during the 2 years before the diagnosis of hearing impairment was compared between the hearing impairment group and the control group using conditional logistic regression analysis. Additional analyses were conducted according to age and sex. The number of days of previous statin use was not different between the hearing impairment group and the control group (adjusted odds ratio [aOR] = 0.94, 95% confidence interval (CI) = 0.86–1.02, P = 0.118). According to age, in the ≥ 70-year-old group, those with hearing impairment had 11% lower rates of previous statin use than those in the control group (aOR = 0.89, 95% CI = 0.80–0.99, P = 0.039). According to sex, in the male group, 12% lower rates of previous statin use were observed among those with hearing impairment than among those in the control group (aOR = 0.88, 95% CI = 0.79–0.99, P = 0.037). Previous statin use might have an effect on reducing the prevalence of hearing impairment in elderly individuals and men.

We report three additional cases of intra-articular acetabular osteochondroma in multiple hereditary exostoses patients in order to raise the awareness of this rare location, to prompt early diagnosis, and to present various treatment options according to the patient's condition. A 2.5-year-old boy presenting with an out-toeing gait had a large acetabular osteochondroma causing lateral displacement of the femoral head and acetabular dysplasia. Mass excision through hip subluxation via anterior approach and concomitant Dega osteotomy resulted in a congruent, well-developed, and well-covered hip joint at 11-year follow-up. A 10-year-old boy showing a pedunculated osteochondroma arising from the triradiate cartilage was successfully treated by arthroscopic excision. Normal development of the hip joint was observed at skeletal maturity. A 6-year-old boy presented with a painless limp. Acetabular osteochondroma could be confirmed by computed tomography scan, which was excised through hip subluxation by anterior approach. Persistent coxa valga and femoral head uncovering were addressed by femoral varization osteotomy at 9 years of age. A high index of suspicion is required to detect a lesion at this rare location. Various procedures may be considered according to the pathoanatomy. Acetabular dysplasia, coxa valga, and femoroacetabular impingement by femur neck mass, if associated, should be addressed in due time.

Bone age is considered an indicator for the diagnosis of precocious or delayed puberty and a predictor of adult height. We aimed to evaluate the performance of a deep neural network model in assessing rapidly advancing bone age during puberty using elbow radiographs. In all, 4437 anteroposterior and lateral pairs of elbow radiographs were obtained from pubertal individuals from two institutions to implement and validate a deep neural network model. The reference standard bone age was established by five trained researchers using the Sauvegrain method, a scoring system based on the shapes of the lateral condyle, trochlea, olecranon apophysis, and proximal radial epiphysis. A test set (n = 141) was obtained from an external institution. The differences between the assessment of the model and that of reviewers were compared. The mean absolute difference (MAD) in bone age estimation between the model and reviewers was 0.15 years on internal validation. In the test set, the MAD between the model and the five experts ranged from 0.19 to 0.30 years. Compared with the reference standard, the MAD was 0.22 years. Interobserver agreement was excellent among reviewers (ICC: 0.99) and between the model and the reviewers (ICC: 0.98). In the subpart analysis, the olecranon apophysis exhibited the highest accuracy (74.5%), followed by the trochlea (73.7%), lateral condyle (73.7%), and radial epiphysis (63.1%). Assessment of rapidly advancing bone age during puberty on elbow radiographs using our deep neural network model was similar to that of experts. • Bone age during puberty is particularly important for patients with scoliosis or limb-length discrepancy to determine the phase of the disease, which influences the timing and method of surgery. • The commonly used hand radiographs–based methods have limitations in assessing bone age during puberty due to the less prominent morphological changes of the hand and wrist bones in this period. • A deep neural network model trained with elbow radiographs exhibited similar performance to human experts on estimating rapidly advancing bone age during puberty.

We argue why interpretability should have primacy alongside empiricism for several reasons: first, if machine learning (ML) models are beginning to render some of the high-risk healthcare decisions instead of clinicians, these models pose a novel medicolegal and ethical frontier that is incompletely addressed by current methods of appraising medical interventions like pharmacological therapies; second, a number of judicial precedents underpinning medical liability and negligence are compromised when ‘autonomous’ ML recommendations are considered to be en par with human instruction in specific contexts; third, explainable algorithms may be more amenable to the ascertainment and minimisation of biases, with repercussions for racial equity as well as scientific reproducibility and generalisability. We conclude with some reasons for the ineludible importance of interpretability, such as the establishment of trust, in overcoming perhaps the most difficult challenge ML will face in a high-stakes environment like healthcare: professional and public acceptance.

This study investigated the association of previous use of proton pump inhibitors (PPIs) with the rate of hearing impairment. The ≥40-year-old population in the Korean National Health Insurance Service-Health Screening Cohort was enrolled. The 6626 registered hearing-impaired patients were matched with 508,240 control participants for age, sex, income, region of residence, and index date (date of hearing impairment diagnosis). The prescription histories of PPIs were collected for 2 years before the index date. The odds ratios of the duration of PPI use for hearing impairment were analyzed using conditional logistic regression. Subgroups of age/sex and severity of hearing impairments were additionally analyzed for the relation of PPI use with hearing impairment. PPI use for 30–365 days was associated with a 1.65-times higher odds of hearing impairment (95% confidence interval (CI) = 1.47–1.86 for 30–365 days of PPI medication). PPI use for ≥365 days was also related to 1.52-times higher odds of hearing impairment (95% CI = 1.35–1.72, p &lt, 0.001). All age and sex subgroups demonstrated a positive association between PPI use and hearing impairment. Severe hearing impairment showed consistently higher odds of a relation with PPI use. PPI use was associated with an increased rate of hearing impairment.

Background Alcohol consumption is one of the modifiable risk factors for intracerebral hemorrhage, which accounts for approximately 10–20% of all strokes worldwide. We evaluated the association of stroke with genetic polymorphisms in the alcohol metabolizing genes, alcohol dehydrogenase 1B (ADH1B, rs1229984) and aldehyde dehydrogenase 2 (ALDH2, rs671) genes based on alcohol consumption. Methods Data were available for 19,500 Taiwan Biobank (TWB) participants. We used logistic regression models to test for associations between genetic variants and stroke. Overall, there were 890 individuals with ischemic stroke, 70 with hemorrhagic stroke, and 16,837 control individuals. Participants with ischemic but not hemorrhagic stroke were older than their control individuals (mean ± SE, 58.47 ± 8.17 vs. 48.33 ± 10.90 years, p Conclusions Our study suggests that the ADH1B rs1229984 TC + CC genotype and alcohol exposure of at least 150 ml/week may increase the risk of developing hemorrhagic stroke among Taiwanese adults.

Paraprobiotics, inactivated microbial cells, regulate immune system and exhibit antioxidant and anti-inflammatory activities in patients with weakened immunity or the elderly. This study evaluated the anti-tumor effects of heat-killed

In terms of public health, obesity and overweight have become major concerns worldwide. Nevertheless, regarding body composition, it is important to have a more precise understanding of the fat-to-muscle ratio. Hence, this study aimed to adopt bioelectrical impedance measurements to test body fat percentage (BF%) and to determine the associations between health-related physical fitness and both body fat (BF) distribution and BF obesity risk in Taiwanese adults. We conducted a cross-sectional study and reviewed data derived from Taiwan’s Scientific Physical Fitness Survey. From the database, responses from 17,970 participants aged 23–64 years were collected in this study. Each participant completed a series of health-related physical fitness measurements, including cardiorespiratory fitness (3 min of a progressive knee-up and step (3MPKS) test), muscular fitness (hand-grip strength), and flexibility (sit-and-reach test). The BF% of each participant was assessed using the bioelectrical impedance analysis method. BF% was negatively associated with low performance on the 3MPKS (β = 11.314, p < 0.0001 for men; β = 12.308, p < 0.0001 for women), hand-grip strength (β = 2.071, p < 0.0001 for men; β = 0.859, p < 0.0001 for women), and sit-and-reach (β = 0.337, p = 0.008 for women) tests but was positively associated with sit-and-reach (β = −0.394, p = 0.004 for men). A risk of BF obesity for low performance of 3MPKS (odds ratio (OR) = 26.554, p < 0.0001 for men; OR = 25.808, p < 0.0001 for women), hand-grip strength (OR = 1.682, p < 0.0001 for men; OR = 1.234, p < 0.0001 for women), and sit-and-reach (OR = 1.142, p = 0.007 for women) tests was observed. These results suggest that low levels of cardiorespiratory fitness, muscular fitness, and flexibility are associated with an increased risk of BF obesity.

Although the modified barium swallowing study (MBSS) is considered the gold standard for assessing aspiration risk, aspiration of lipid-soluble barium can cause chemical pneumonitis or impair radiologic interpretation of the lungs. Water-soluble contrast agents (WSCAs) may avoid these complications while maintaining sensitivity on aspiration. This prospective, observational, case-control cohort trial evaluated all patients3 years old referred for swallowing study from September 2015 to November 2017. Repeat evaluations of individuals were excluded. High-risk patients were evaluated by WSCA (iohexol)-based swallowing study (WSS) and others by MBSS. The study included 829 evaluations of 762 patients. After excluding 74 evaluations, 365 WSSs and 390 MBSSs were performed. The most frequent underlying condition was brain lesion, followed by aspiration pneumonia. Aspiration occurred more frequently in WSS (147 patients: 40.3%) than in MBSS (36 patients: 9.2%) (P = .00). However, neither aspiration volume (6.72 cc [3.09-10.35] vs 5.53 cc [2.21-8.85]) nor radiographic alterations differed between the 2 groups (P.05). Moreover, the swallowed (16.62 cc [8.45-24.79]) and aspirated amounts of iohexol were not correlated with radiologic changes or deterioration (P.05). Switching to oral feeding following WSS was more frequent (164 patients: 44.9%), whereas aspiration pneumonia was not (P = .00). WSS did not prolong the interval to patient discharge (P = .06) or induce an allergic reaction or chemotoxicity over 1 week. The absence of aspiration-induced complications and adverse drug effects suggests that, compared with MBSS, WSS may increase aspiration sensitivity and early switching to oral feeding.

Long diagnostic wait times hinder international efforts to address antibiotic resistance in M. tuberculosis. Pathogen whole genome sequencing, coupled with statistical and machine learning models, offers a promising solution. However, generalizability and clinical adoption have been limited by a lack of interpretability, especially in deep learning methods. Here, we present two deep convolutional neural networks that predict antibiotic resistance phenotypes of M. tuberculosis isolates: a multi-drug CNN (MD-CNN), that predicts resistance to 13 antibiotics based on 18 genomic loci, with AUCs 82.6-99.5% and higher sensitivity than state-of-the-art methods; and a set of 13 single-drug CNNs (SD-CNN) with AUCs 80.1-97.1% and higher specificity than the previous state-of-the-art. Using saliency methods to evaluate the contribution of input sequence features to the SD-CNN predictions, we identify 18 sites in the genome not previously associated with resistance. The CNN models permit functional variant discovery, biologically meaningful interpretation, and clinical applicability.

MED-02 is a complex supplement containing two probiotic strains