Kimura’s disease: A clinicopathological study of 23 cases

IntroductionKimura’s disease (KD) is an uncommon lymphoproliferative fibroinflammatory disorder. Patients present with head and neck subcutaneous nodules with or without lymphadenopathy. Peripheral blood eosinophilia and elevated serum immunoglobulin E (IgE) levels are typical. This study was designed to delineate the clinicopathological features, pattern of care, and disease course of 23 Taiwanese patients with KD.MethodsWe retrospectively analyzed the clinical data of 23 consecutive cases (16 male and 7 female; age at diagnosis: 12–77 years) of KD diagnosed at our institution from 2015 to 2020.ResultsThe median time from presentation to diagnosis was 1 month. Twenty-one patients presented with unilateral or bilateral head and neck masses. The remaining two presented with right flank and right arm lesions, respectively. Peripheral blood eosinophilia was observed in nine, and elevated IgE levels were observed in four. All were diagnosed using either excisional or core-needle biopsy. Seven patients underwent fine needle aspiration without a diagnostic yield. Salivary gland and lymph node involvement was observed in three and seven patients, respectively. Most lesions showed tissue eosinophilia (100%) and florid follicular hyperplasia (78.26%). Three cases had histological KD-IgG4-RD overlap and three had comorbid IgG4-RD were recognized. Thirteen patients underwent surgical resection, one received adjuvant therapy, and two received prednisolone monotherapy.ConclusionKD should be considered in patients with subcutaneous masses, eosinophilia, and elevated IgE levels. Biopsy remains the gold standard of diagnosis. Increased recruitment of IgG4+ plasma cells is a common feature. Consideration of IgG4-RD in all KD patients may be prudent

Mechanical Characterization of Rabbit Pulmonary Vein Sleeves in In Vitro Intact Ring Preparation

BackgroundPulmonary vein (PV) sleeves, composed of cardiomyocytes, play certain roles in arrhythmogenesis. In the literature, it has been frequently reported that PV sleeves possess intrinsic spontaneous pacemaking activity and triggered activity in normal dogs and rabbits. In contrast, other research groups presented totally opposite findings which showed absence of such pacemakers in dogs, rabbits and rats. The present study was designed to clarify this puzzle and contradiction.MethodsA novel methodology using in vitro experimentation was used to examine the electromechanical activity of whole segments of PV sleeves. The ring preparation was composed of a small piece of left atrial (LA) free wall, PV ostium and sleeve from rabbits. A circumferential contraction of the PV sleeve was measured when the preparation was electrically driven from the LA free wall. Mechanical force of the ring preparation was measured using a force transducer. The action potentials were recorded using conventional intracellular recording technique in strip preparation.ResultsIn 15 rabbits, no spontaneous pacemaking activity or triggered activity was found in the in vitro ring preparation of PV sleeve. The circumferential contraction of PV sleeves was external calcium-dependent. Frequency-force relation displayed a negative staircase at 0.1–0.5 Hz and a positive staircase at 1–5 Hz. Post-rest potentiation was prominent between 15 s and 120 s. Intracellular action potential recording did not display any automaticity or triggered activity in PV sleeves.ConclusionIn an intact ring preparation of rabbit PV sleeves, intrinsic spontaneous pacemaking activity or triggered activity was not found

Yang-Dan-Tang, Identified from 15 Chinese Herbal Formulae, Inhibits Human Lung Cancer Cell Proliferation via Cell Cycle Arrest

Lung cancer has long been one of the most deadly forms of cancer. The majority of lung cancers are of the non-small-cell lung cancer (NSCLC) type. Here we used the non-small-cell lung carcinoma cell line A549 to screen 15 different traditional Chinese herbal medicine (CHM) formulae to explore the possible mechanisms of alternative medicine in lung cancer therapy. We identified three formulae (Formulae 3, 5, and 14) that substantially decreased the survival of A549 cells but did not affect MRC5 normal lung tissue cells. Formula 14, Yang-Dan-Tang, a modified decoction of Ramulus Cinnamomi Cassiae, was chosen for further characterization. Flow cytometry analysis showed that treatment of Formula 14 induced cell cycle arrest in G1 and G2 phase without causing significant cell death. These results were also confirmed by Western blot analysis, with decreased expression of G1/S and G2/M promoting cell cycle machinery including cyclin D3, cyclin B1, CDK4, and CDK6. This study provides further insight into the possible working mechanism of Yang-Dan-Tang in patients

Effectiveness and Limitations of Hand Hygiene Promotion on Decreasing Healthcare–Associated Infections

BACKGROUND: Limited data describe the sustained impact of hand hygiene programs (HHPs) implemented in teaching hospitals, where the burden of healthcare-associated infections (HAIs) is high. We use a quasi-experimental, before and after, study design with prospective hospital-wide surveillance of HAIs to assess the cost effectiveness of HHPs. METHODS AND FINDINGS: A 4-year hospital-wide HHP, with particular emphasis on using an alcohol-based hand rub, was implemented in April 2004 at a 2,200-bed teaching hospital in Taiwan. Compliance was measured by direct observation and the use of hand rub products. Poisson regression analyses were employed to evaluate the densities and trends of HAIs during the preintervention (January 1999 to March 2004) and intervention (April 2004 to December 2007) periods. The economic impact was estimated based on a case-control study in Taiwan. We observed 8,420 opportunities for hand hygiene during the study period. Compliance improved from 43.3% in April 2004 to 95.6% in 2007 (p<.001), and was closely correlated with increased consumption of the alcohol-based hand rub (r = 0.9399). The disease severity score (Charlson comorbidity index) increased (p = .002) during the intervention period. Nevertheless, we observed an 8.9% decrease in HAIs and a decline in the occurrence of bloodstream, methicillin-resistant Staphylococcus aureus, extensively drug-resistant Acinetobacter baumannii, and intensive care unit infections. The intervention had no discernable impact on HAI rates in the hematology/oncology wards. The net benefit of the HHP was US$5,289,364, and the benefit-cost ratio was 23.7 with a 3% discount rate. CONCLUSIONS: Implementation of a HHP reduces preventable HAIs and is cost effective

Renal and survival benefits of seventeen prescribed Chinese herbal medicines against oxidative-inflammatory stress in systemic lupus erythematosus patients with chronic kidney disease: a real-world longitudinal study

Background: Systemic lupus erythematosus (SLE) significantly links to LN, a type of CKD with high mortality despite modern Western treatments. About 70% of SLE patients develop LN, and 30% advance to end-stage renal disease (ESRD). Concerns about glucocorticoid side effects and LN worsening due to oxidative stress prompt alternative treatment searches. In Taiwan, over 85% of SLE patients opt for complementary methods, especially Chinese herbal medicine (CHM). We pinpointed seventeen CHMs for SLE (PRCHMSLE) with antioxidative and anti-inflammatory properties from national health insurance data (2000–2017). Our primary aim was to assess their impact on renal and survival outcomes in SLE patients progressing to CKD (SLE-CKD), with a secondary focus on the risks of hospitalization and hyperkalemia.Methods: We established a propensity-matched cohort of 1,188 patients with SLE-CKD, comprising 594 PRCHMSLE users and 594 nonusers. We employed Cox proportional hazards models and restricted mean survival time (RMST) analyses to assess the renal and survival outcomes of PRCHMSLE users. Moreover, we performed pooling and network analyses, specifically focusing on the renal effects linked to PRCHMSLE.Results: PRCHMSLE use was associated with decreased adjusted hazard ratios for ESRD (0.45; 95% confidence interval, 0.25–0.79, p = 0.006), all-cause mortality (0.56; 0.43–0.75, p &lt; 0.0001), non-cardiovascular mortality (0.56; 0.42–0.75, p &lt; 0.0001), and hospitalization (0.72; 0.52–0.96, p = 0.009). Hyperkalemia risk did not increase. Significant differences in RMST were observed: 0.57 years (95% confidence interval, 0.19–0.95, p = 0.004) for ESRD, 1.22 years (0.63–1.82, p &lt; 0.0001) for all-cause mortality, and 1.21 years (0.62–1.80, p &lt; 0.0001) for non-cardiovascular mortality, favoring PRCHMSLE use. Notably renoprotective PRCHMSLE included Gan-Lu-Ying, Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), Jia-Wei-Xiao-Yao-San, and Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi). Network analysis highlighted primary treatment strategies with central components like Liu-Wei-Di-Huang-Wan, Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi), Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), and Zhi-Bai-Di-Huang-Wan.Conclusion: This work underscores the pronounced renal and survival benefits associated with the seventeen PRCHMSLE in the treatment of SLE-CKD, concurrently mitigating the risks of hospitalization and hyperkalemia. This highlights their potential as alternative treatment options for individuals with this condition

Predicting the Severity and Prognosis of Trismus after Intensity-Modulated Radiation Therapy for Oral Cancer Patients by Magnetic Resonance Imaging

To develop magnetic resonance imaging (MRI) indicators to predict trismus outcome for post-operative oral cavity cancer patients who received adjuvant intensity-modulated radiation therapy (IMRT), 22 patients with oral cancer treated with IMRT were studied over a two-year period. Signal abnormality scores (SA scores) were computed from Likert-type ratings of the abnormalities of nine masticator structures and compared with the Mann-Whitney U-test and Kruskal–Wallis one-way ANOVA test between groups. Seventeen patients (77.3%) experienced different degrees of trismus during the two-year follow-up period. The SA score correlated with the trismus grade (r = 0.52, p<0.005). Patients having progressive trismus had higher mean doses of radiation to multiple structures, including the masticator and lateral pterygoid muscles, and the parotid gland (p<0.05). In addition, this group also had higher SA-masticator muscle dose product at 6 months and SA scores at 12 months (p<0.05). At the optimum cut-off points of 0.38 for the propensity score, the sensitivity was 100% and the specificity was 93% for predicting the prognosis of the trismus patients. The SA score, as determined using MRI, can reflect the radiation injury and correlate to trismus severity. Together with the radiation dose, it could serve as a useful biomarker to predict the outcome and guide the management of trismus following radiation therapy

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Recapitulation of Fibromatosis Nodule by Multipotential Stem Cells in Immunodeficient Mice

Musculoskeletal fibromatosis remains a disease of unknown etiology. Surgical excision is the standard of care, but the recurrence rate remains high. Superficial fibromatosis typically presents as subcutaneous nodules caused by rapid myofibroblast proliferation followed by slow involution to dense acellular fibrosis. In this study, we demonstrate that fibromatosis stem cells (FSCs) can be isolated from palmar nodules but not from cord or normal palm tissues. We found that FSCs express surface markers such as CD29, CD44, CD73, CD90, CD105, and CD166 but do not express CD34, CD45, or CD133. We also found that FSCs are capable of expanding up to 20 passages, that these cells include myofibroblasts, osteoblasts, adipocytes, chondrocytes, hepatocytes, and neural cells, and that these cells possess multipotentiality to develop into the three germ layer cells. When implanted beneath the dorsal skin of nude mice, FSCs recapitulated human fibromatosis nodules. Two weeks after implantation, the cells expressed immunodiagnostic markers for myofibroblasts such as α-smooth muscle actin and type III collagen. Two months after implantation, there were fewer myofibroblasts and type I collagen became evident. Treatment with the antifibrogenic compound Trichostatin A (TSA) inhibited the proliferation and differentiation of FSCs in vitro. Treatment with TSA before or after implantation blocked formation of fibromatosis nodules. These results suggest that FSCs are the cellular origin of fibromatosis and that these cells may provide a promising model for developing new therapeutic interventions

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

The global response: How cities and provinces around the globe tackled Covid-19 outbreaks in 2021

Background: Tackling the spread of COVID-19 remains a crucial part of ending the pandemic. Its highly contagious nature and constant evolution coupled with a relative lack of immunity make the virus difficult to control. For this, various strategies have been proposed and adopted including limiting contact, social isolation, vaccination, contact tracing, etc. However, given the heterogeneity in the enforcement of these strategies and constant fluctuations in the strictness levels of these strategies, it becomes challenging to assess the true impact of these strategies in controlling the spread of COVID-19.Methods: In the present study, we evaluated various transmission control measures that were imposed in 10 global urban cities and provinces in 2021 Bangkok, Gauteng, Ho Chi Minh City, Jakarta, London, Manila City, New Delhi, New York City, Singapore, and Tokyo.Findings: Based on our analysis, we herein propose the population-level Swiss cheese model for the failures and pit-falls in various strategies that each of these cities and provinces had. Furthermore, whilst all the evaluated cities and provinces took a different personalized approach to managing the pandemic, what remained common was dynamic enforcement and monitoring of breaches of each barrier of protection. The measures taken to reinforce the barriers were adjusted continuously based on the evolving epidemiological situation.Interpretation: How an individual city or province handled the pandemic profoundly affected and determined how the entire country handled the pandemic since the chain of transmission needs to be broken at the very grassroot level to achieve nationwide control