Search

Abstract This study examined the sex-specific mortality risk and causes of death soon after hip fracture in Taiwan. The objective of this study was to evaluate the 30-day mortality risk and cause of death in patients with hip fracture and identify its associated risk factors. We conducted a retrospective cohort study using data from the National Health Insurance Research Database in Taiwan from 2000 to 2015. This study included patients aged 50 years or older who were admitted to a hospital with a hip fracture diagnosis for the first time. Of 285,891 patients hospitalized for their first hip fracture, 8,505 (2.98%) died within 30 days. The mortality risk of hip fracture declined from 3.76% in 2000 to 2.92% in 2015. Circulatory system diseases like ischemic heart disease and cerebrovascular disease were the most common cause of death and accounted for 22% of deaths within 30 days after fracture. Accidents and unintentional injuries caused 18% of deaths, followed by malignant neoplasms in 10% of deaths. Multivariate Cox regression identified older age, male sex, higher Charlson Comorbidity Index (CCI), suburban or rural residence, and lower income as risk factors for hip fracture mortality. The 30-day mortality risk of hip fractures has decreased but remains correlated with male sex, older age, and comorbidities. Circulatory diseases were the main cause of death. Early identification and treatment by experienced clinicians may optimize outcomes, minimize complications, and reduce mortality risk in the 30 days following hip fracture.

ABSTRACT Background Intraoperative radiotherapy (IORT) is considered a de‐escalating adjuvant treatment for breast cancer low‐risk patients. However, the broader criteria applied by the Taiwan IORT Study Cooperative Group led to an increased rate of locoregional recurrence (LRR) among patients receiving only IORT. Consequently, we revised the criteria for sole IORT treatment to include patients who meet the American Society for Radiation Oncology (ASTRO) eligibility standards. This study aims to investigate how aligning treatment strategies with ASTRO guidelines impacts oncological outcomes in patients receiving IORT. Methods From September 2014 to March 2022, a retrospective review of 632 patients with invasive breast cancer undergoing breast‐conserving surgery assessed outcomes following External Beam Radiation Therapy (EBRT), sole IORT, or IORT combined with supplemental EBRT (IORT+boost), with a mean follow‐up period of 4.71 ± 2.10 years. Strategic modifications following the ASTRO guidelines were implemented in April 2021 for sole IORT recipients. Results ASTRO‐suitable patients had significantly lower rates of LRR (0.00% vs. 10.64%), distant metastasis (0.00% vs. 4.00%), and any recurrence (0.00% vs. 7.79%) than non‐suitable patients (p

Abstract Background This study aimed to ascertain if the incorporation of intensity‐modulated radiotherapy (IMRT) with chemotherapy (CTx) offered any advantages for patients diagnosed with stage pT3N0 rectal cancer located in the proximal (upper) region following a complete total mesorectum excision (TME). Methods We retrospectively examined medical records of stage II/III rectal cancer patients who had undergone CTx or concurrent chemoradiation (CCRT) with IMRT after a successful TME. We juxtaposed a variety of survival outcomes across two patient cohorts. Each outcome was further classified according to Gunderson's risk stratification between proximal and distal (middle and low) rectal cancer patients, and we evaluated the factors associated with each outcome. Results The median follow‐up duration was 4.9 years. Our research comprised 236 rectal adenocarcinoma patients treated at our institution between 2007 and 2019. They received either the CTx (n = 135) or the CCRT (n = 101) with 10‐year locoregional recurrence‐free survival (LRRFS) of 90.1% and 96.1%, respectively (p = 0.163). However, after performing multivariate adjustments, a pattern emerged hinting at a better LRRFS for the CCRT group (p = 0.052). Perforation had a strong correlation with locoregional recurrence. No significant differences were observed in other survival between the two treatment arms and their respective subgroups. The CCRT group witnessed significantly higher immediate and chronic complications with p = 0.007 and 0.009, respectively. The CCRT group had two secondary cancer‐related fatalities (2%, one attributed to IMRT), and another reported by the CTx group (1%). The sole classified locoregional recurrence within the cohort of 37 individuals treated with CTx for proximal pT3N0 rectal cancer was, in fact, the development of sigmoid colon cancer. Conclusion The results suggest that for patients with proximal pT3N0 rectal cancer post‐TME, IMRT is better when not combined with CTx, except in highly perilous scenarios or those involving perforation.

Abstract Despite the abundance of research on the risk factors for mortality following hip fracture surgery, there has been a dearth of studies on prediction models in this population. The objective of this research was to explore the influencing factors and construct a clinical nomogram to predict one-year postoperative mortality in patients with hip fracture surgeries. Using the Ditmanson Research Database (DRD), we included 2333 subjects, aged ≥ 50 years who underwent hip fracture surgery between October, 2008 and August, 2021. The endpoint was all-cause mortality. A least absolute shrinkage and selection operator (LASSO) derived Cox regression was performed to select the independent predictors of one-year postoperative mortality. A nomogram was built for predicting one-year postoperative mortality. The prognostic performance of nomogram was evaluated. On the basis of tertiary points in a nomogram, the patients were divided into low, middle and high risk groups, and compared by the Kaplan–Meier analysis. Within 1 year after hip fracture surgery, 274 patients (11.74%) died. Variables retained in the final model comprised age, sex, length of stay, RBC transfusions, hemoglobin, platelet, and eGFR. The AUC for one-year mortality predictions were 0.717 (95% CI = 0.685–0.749). The Kaplan–Meier curves were significantly different among the three risk groups (p

Abstract Background The reactivation of herpes zoster (HZ) is associated with disease stress. However, the relationship between chondromalacia patella (CMP) and HZ remains poorly understood. This study investigated the relationship between CMP and the risk of developing HZ. Methods Data were collected from the Taiwan’s National Health Insurance Research Database. Patients with CMP diagnosed between 2000 and 2017 were assigned to the case group; patients without CMP were randomly selected from the same database and paired with controls matched by age and sex. The primary outcome was a diagnosis of HZ. All patients were followed until their diagnosis of HZ, their withdrawal from the NHI program, their death, or the end of 2017, whichever was earliest. The risk of developing HZ was compared between the case and control groups. Results In total, 22,710 patients with CMP and 90,840 matched controls were enrolled. The overall incidence rates of HZ in the CMP and control cohorts were 7.94 and 7.35 per 1,000 person-years, respectively. After potential confounders were controlled for, the case group exhibited a higher risk of HZ than did the control group [adjusted hazard ratio (aHR) = 1.06, p

Alcohol consumption causes alcoholic liver diseases (ALD). The aim of this study investigated whether the mechanisms of the effects of dehulled adlay on ALD by using a chronic ethanol feeding plus single binge model. Rats were pair-fed with a control liquid diets (C), ethanol liquid diet (E), or ethanol + dehulled adlay diet (EA) containing equal energy and dietary fiber for 5 weeks. The results revealed that dietary dehulled adlay ameliorated ethanol-induced increases in oxidative stress and inflammation and modulating nuclear factor erythroid 2-related factor 2-inflammasome and Toll-like receptor-4 signaling pathways. Furthermore, dehulled adlay arrested the decrease in occludin expression in the ileum and mitigated changes in the diversity and composition of the gut microbiota caused by alcohol exposure, which were significantly correlated with ALD biomarkers. Our results suggest that dietary dehulled adlay prevents ALD progression possibly by reducing hepatic oxidative stress and inflammation, and modulating gut dysbiosis.

Background:. There is no consensus on the duration of prophylactic antibiotic use for autologous breast reconstruction after mastectomy. We attempted to standardize the use of prophylactic antibiotics after mastectomy using a deep inferior epigastric perforator flap for the breast reconstruction procedure. Methods:. This retrospective case series included 108 patients who underwent immediate breast reconstruction with a deep inferior epigastric perforator flap at the Ditmanson Medical Foundation Chia-Yi Christian Hospital between 2012 and 2019. Patients were divided into three groups based on the duration of prophylactic antibiotic administration (1, 3, and >7 days) for patients with drains. Data were analyzed between January and April 2021. Results:. The prevalence of surgical site infection in the breast was 0.93% (1/108), and in the abdomen it was 0%. The patient groups did not differ by age, body mass index, smoking status, or neoadjuvant chemotherapy. Only one patient experienced surgical site infection in the breast after half-deep necrosis of the inferior epigastric perforator flap. There were no significant differences in surgical site infection based on the duration of prophylactic antibiotic use. The operation time, methods of breast surgery, volume of fluid drainage in the first 3 days of the abdominal and breast drains, and day of removal of the abdominal and breast drains did not affect surgical site infection. Conclusion:. Based on these data, we do not recommend extending prophylactic antibiotics beyond 24 hours in deep inferior epigastric perforator reconstruction.

Caulerpa lentillifera (CL), also called sea grape, is a type of edible green alga which was reported to have antioxidative and immunomodulatory potential. This study aimed to investigate the hepatoprotective effects of CL in a rat model of chronic ethanol exposure. Wistar rats were assigned to four groups and supplied with an isocaloric control liquid diet (group C), an ethanol liquid diet (group E), a control liquid diet supplemented with 5% CL (group CC), or an ethanol liquid diet supplemented with 5% CL (group EC) for a 12-week experimental period. Ethanol feeding induced steatosis, inflammation, and changes in the gut microbiota by the end of the study, whereas CL supplementation significantly improved liver injuries and decreased circulatory endotoxin levels. Moreover, we also found that CL reversed ethanol-induced elevation of hepatic toll-like receptor 4 (TLR4), MyD88 protein expression, the phosphorylated-nuclear factor (NF)-κB-to–NF–κB ratio, and proinflammatory cytokine concentrations. Additionally, CL also increased the abundance of Akkermansia and tight junction proteins and diminished the Firmicutes-to-Bacteroidetes ratio. Dietary CL inhibited the progression of alcoholic liver disease, and some of the possible mechanisms may be strengthening the intestinal barrier function, alleviating dysbiosis, and modulating the TLR4 pathway.

BackgroundStroke survivors are prone to osteoporosis and fractures. However, bone mineral density (BMD) testing and osteoporosis treatment were underutilized in patients with recent stroke. We aimed to examine whether stroke has an impact on the utilization of BMD testing and osteoporosis treatment as well as the determinants of their utilization in stroke patients using nationwide population-based data in Taiwan.MethodsWe identified patients aged 55 years and older who were hospitalized for hemorrhagic or ischemic stroke as the stroke cohort, and age- and sex-matched patients hospitalized for reasons other than stroke, fracture, or fall as the non-stroke cohort. We used the Fine-Gray sub-distribution hazard competing risk regression model to determine the predictors for BMD testing and osteoporosis treatment.ResultsA total of 32997 stroke patients and 32997 age- and sex-matched controls comprised the stroke and non-stroke cohorts, respectively. BMD testing and osteoporosis treatment were performed in 1.0% and 5.2% of the stroke patients, respectively, within one year after hospitalization while these measures were performed in 0.8% and 4.7% of the controls. Stroke patients were more likely to receive BMD testing (adjusted hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.11–1.58) and osteoporosis treatment (adjusted HR 1.19; 95% CI 1.11–1.29). Female sex, osteoporosis, prior BMD testing, and low-trauma fractures after stroke increased the likelihood of using BMD testing and osteoporosis treatment whereas greater stroke severity reduced the likelihood of receiving both measures.ConclusionsBoth BMD testing and osteoporosis treatment were underutilized among stroke survivors even though they had a higher chance of receiving both measures than non-stroke patients.

Abstract The predictive value of the pretreatment prognostic nutritional index (PNI) for head and neck cancer (HNC) remains controversial. We conducted a meta-analysis to assess the predictive value of PNI in HNC patients. A systematic search through internet databases including PubMed, Embase, and Cochrane Library for qualified studies estimating the association of PNI with HNC patient survival was performed. Overall survival (OS), progression-free survival (PFS), disease-specific survival (DSS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) data were collected and evaluated. A random-effects model was used to calculate the pooled hazard ratios (pHRs) and corresponding 95% confidence intervals (CIs). A total of 7815 HNC patients from 14 eligible studies were involved. Pooled analysis showed that low pretreatment PNI was correlated with poor OS (pHR: 1.93, 95% CI 1.62–2.30, p

Abstract Introduction Intraoperative radiotherapy (IORT) is more convenient than standard whole breast external beam radiotherapy (EBRT) as a sole adjuvant radiotherapy for breast cancer. The impact of age on breast cancer course and treatment strategy is still under investigation, and the peak age for breast cancer in Taiwan is much younger than that in Western countries. We aimed to review the oncological outcomes of sole IORT compared with standard EBRT in a country with younger breast cancer patients. Patients and methods We reviewed patients with invasive breast cancer who received breast-conserving surgery (BCS) from September 2014 to December 2016. The clinicopathologic characteristics and oncological outcomes of eligible patients who received EBRT or IORT as sole adjuvant radiotherapy after BCS were collected and reviewed. Results A total of 170 patients were enrolled with a mean follow-up time of 3.53 ± 0.82 years. The risk of locoregional recurrence was 2.44% for EBRT versus 10.64% for IORT (p = 0.024). IORT was a significant risk factor of locoregional recurrence (p = 0.005). The hazard ratios (HRs) for locoregional recurrence in the IORT group compared with the EBRT group were significantly higher in non-suitable risk group patients (HR = 7.02, p = 0.009) and in patients under 50 years old (HR = 10.42, p = 0.011). Conclusions Locoregional recurrence was significantly higher in patients who received IORT than in those who underwent EBRT. IORT should not be used alone in patients under 50 years old who do not belong to a suitable group.

Abstract Salivary gland epithelial cells (SGECs) have been implicated in the pathogenesis of Sjögren’s syndrome due to aberrant antigen-presentation function. This study examined the hypothesis that oral dysbiosis modulates the antigen-presentation function of SGECs, which regulates CD4 T cell proliferation in primary Sjögren’s syndrome (pSS). Saliva samples from 8 pSS patients and 16 healthy subjects were analyzed for bacterial 16S ribosomal DNA. As a result, 39 differentially abundant taxa were identified. Among them, the phylum Proteobacteria comprised 21 taxa, and this phylum was mostly enriched in the healthy controls. The proteobacterium Haemophilus parainfluenzae was enriched in the healthy controls, with the greatest effect size at the species level. Treatment of A253 cells in vitro with H. parainfluenzae upregulated PD-L1 expression, and H. parainfluenzae-pretreated A253 cells suppressed CD4 T cell proliferation. The suppression was partially reversed by PD-L1 blockade. Among low-grade xerostomia patients, salivary abundance of H. parainfluenzae decreased in pSS patients compared to that in non-pSS sicca patients. Our findings suggest that H. parainfluenzae may be an immunomodulatory commensal bacterium in pSS.

Abstract Background It has been shown that iron deficiency anemia (IDA) is associated with psychosocial consequences and psychiatric morbidity. However, the association between adults with IDA and psychiatric disorders has not been clarified. The purpose of this study was to investigate the psychiatric disorder morbidity of an IDA group in comparison with a non-IDA group and to examine the risk of psychiatric disorders in IDA patients treated with iron supplementation. Methods All study subjects were 20 years of age or over with newly diagnosed IDA enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. We matched IDA and non-IDA subjects according to age and gender in a 1:2 ratio. Our primary outcome was diagnosis of psychiatric disorders and the patients were monitored until the end of 2013. A multivariate Cox proportional hazards regression model was used to explore the risk of psychiatric disorders in patients with IDA after adjustment for confounders, including demographic characteristics and comorbidities. Results The adjusted hazard ratios (aHRs) of psychiatric disorders was 1.52 (95% CI = 1.45–1.59) in the IDA group compared with the non-IDA group. Among the different types of psychiatric disorders, the IDA group was associated with significantly higher incidence and risks of anxiety disorders, depression, sleep disorders, and psychotic disorders (p

Abstract Background Breastfeeding benefits both mothers and infants. Even though Taiwan national policy promotes exclusive breastfeeding (EBF), the rates in Taiwan are below those in other developed countries. This study aimed to investigate factors associated with EBF cessation at 1 and 2 months postpartum. Methods This study was conducted in a community hospital in southern Taiwan between December 2016 and June 2017. Birth mothers (n = 1077) were interviewed by telephone at 1 and 2 months postpartum to collect information on infant feeding patterns (EBF since birth or not) and reasons for EBF cessation. Multivariate logistic regression models were used to determine risk factors associated with EBF cessation at 1 and 2 months. Results At 1 month, 432 participants (40.1%) maintained EBF. Factors associated with cessation were lack of tertiary education, primiparity, perceived low milk quantity, mother/infant separation, medical condition in mother, inconvenience/fatigue due to breastfeeding, and baby-centered factors. At 2 months, 316 participants (29.3%) maintained EBF. Factors associated with cessation were lack of tertiary education, primiparity, perceived low milk quantity, and return to work. Conclusions Education level, primiparity, perceived low milk quantity, and return to work are associated with premature cessation of EBF in Taiwan. Strategies about health education, family support, and baby-mother friendly environment can be used to achieve higher EBF rate.

Background: The field of physician health is gaining increasing attention; however, most research and interventions have concentrated on factors such as job stress, mental health, and substance abuse. The risks of major cancers in physicians remain unclear. We used a propensity score-matched analysis to investigate the risk of cancer in physicians relative to the general population who had no healthcare-related professional background. Methods: Data were obtained from the National Health Insurance system in Taiwan. The physician cohort contained 29,713 physicians, and each physician was propensity score-matched with a person from the general population. Results: The physicians demonstrated a 0.90-fold lower risk of all-cancers (95% confidence interval [CI] = 0.83 – 0.96) when compared with the general population. Female physicians had a higher risk of cancer than male physicians (adjusted hazard ratio [HR] = 1.59; 95% CI = 1.28 – 1.96). Physicians had higher risks of prostate (HR = 1.26; 95% CI = 1.00 – 1.59) and thyroid cancers (HR = 3.16; 95% CI = 1.69 – 5.90) when compared with the general population. Conclusion: Physicians have lower rates of overall cancer risk than the general population. Female physicians have higher cancer risks than male physicians. Male physicians have higher risks of thyroid and prostate cancer relative to the general population.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in the world. It has been the most prevalent malignancy in Taiwan for consecutive thirteen years. Despite the diversity of its etiologic and pathophysiologic factors, a biological process named as epithelial-mesenchymal transition (EMT) is indispensable in the progression of epithelial cancer. Our aim is to investigate the correlation between the expression of 8 EMT-related proteins (E-cadherin, β-catenin, claudin-1, CD44, N-cadherin, fibronectin, vimentin, S100A4) and the clinicopathologic features of CRC in Taiwan, along with the DNA CpG epigenetic status of CD44 gene. In immunohistochemical assessment, decreased expression of E-cadherin is statistically associated with the progression of cancer stage, while decreased expression of claudin-1 as well as increased β-catenin nuclear translocation and N-cadherin expression is statistically associated with the progression of histopathologic grade. E-cadherin, nuclear β-catenin and claudin-1 are also associated with other important prognostic factors, including nodal metastasis, tumor deposits, and elevated serum CA 19-9 levels. In addition, the left-sided colon and rectal cancers show increased nuclear translocation of β-catenin compared to the right-sided colon cancers, while the rectal cancers show increased fibronectin expression compared to the right-sided and left-sided colon cancers. Moreover, vimentin is aberrantly expressed in one case of signet-ring cell carcinoma. The DNA methylation levels of CD44 gene promoter between the tumoral and non-tumorous tissues by NGS comparison showed statistical difference on six CpG sites. However, such difference may not be sufficient because these DNA methylation proportions are too low to inactivate CD44 gene. Our results demonstrate the expression of E-cadherin, claudin-1, and nuclear β-catenin is closely related to the clinicopathologic prognostic determinants of CRC in Taiwan. The DNA methylation level of CD44 gene and its protein expression, however, show no correlation with the clinicopathologic features in CRC.

Background and Objectives: Direct-acting antiviral agents (DAA) are a safe and highly effective treatment for hepatitis C virus (HCV) infection. However, the uptake of DAA treatment remains a challenge. This study aims to examine the reasons for DAA refusal among HCV patients covered by the Taiwan National Health Insurance system. Materials and Methods: This retrospective observational study covered the period from January 2009 to December 2019 and was conducted at a single hepatitis treatment center in Taiwan. This study involved chart reviews and phone-based surveys to confirm treatment status and refusal causes. To confirm treatment status, subjects with HCV without treatment records were phone-contacted to confirm treatment status. Patients who did not receive treatment were invited back for treatment. If the patient refused, the reason for refusal was discussed. Results: A total of 3566 patients were confirmed with DAA treatment; 418 patients (179 patients who were lost to contact or refused the survey and 239 patients who completed the survey of DAA refusal) were included in the no-DAA-therapy group. Factors associated with receiving DAAs were hemoglobin levels, hepatitis B virus co-infection, and regular gastroenterology visits. Meanwhile, male sex, platelet levels, and primary care physician visits were associated with DAA refusal. The leading causes of treatment refusal were multiple comorbidities, low health literacy, restricted access to hospitals, nursing home residence, and old age. The rate of DAA refusal remains high (10%). Conclusions: The reasons for treatment refusal are multifactorial, and addressing them requires complex interventions.

Abstract Background With advancement of hemodialysis (HD) technique, late fistula failure (LFF) remains a problem significantly affecting life quality of patients. We attempt to identify factors affecting LFF in patients on chronic HD in Taiwan from the National Health Insurance Research Database. Methods This case–control study enrolled patients over 18 years old and who received regular HD for more than 3 months. LFF was defined as the first fistula failure episode beyond 3 months of chronic HD. We analyzed characteristics, comorbidities and medicine and investigated the association factors of LFF by logistic regression model. A trend test was conducted for risk in different provider levels. Sensitivity tests were conducted to test consistency. Results Of 1558 patients recruited, 772 (49.6%) were identified as LFF cases and 786 were identified as controls. The data showed that patients with diabetes mellitus (DM) had 42% increased rate of LFF. Patients receiving more than 10 HD sessions per month had a 90% increased rate of LFF; patients receiving chronic HD in private clinics had a 49% reduction rate of LFF. There were no significant differences in age, dialysis frequency, and comorbidities among different provider levels. There was a significant trend of risk reduction of the event from medical centers, regional hospitals, district hospitals, to private clinics. The sensitivity tests revealed similar results. Conclusions The factors associated with LFF include DM and receiving more HD sessions; on the contrary, receiving HD in private clinics is associated with less risk of LFF.

Colorectal cancer (CRC) is one of the most common cancers worldwide and its incidence is increasing; therefore, an understanding of its oncogenic mechanisms is critical for improving its treatment and management. Methylglyoxal (MGO) has a highly reactive aldehyde group and has been suggested to play a role in oncogenesis. However, no standardized data are currently available on MGO levels in colorectal precancerous and cancerous lesions. We collected 40 matched colorectal tumor and peritumor tissues from patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive cancer (IC). MGO levels increased between LGD, HGD, and IC tumor tissues (215.25 ± 39.69, 267.45 ± 100.61, and 587.36 ± 123.19 μg/g protein, respectively; p = 0.014). The MGO levels in peritumor tissue increased and were significantly higher than MGO levels in tumor tissue (197.99 ± 49.40, 738.09 ± 247.87, 933.41 ± 164.83 μg/g protein, respectively; p = 0.002). Tumor tissue MGO levels did not correlate with age, sex, underlying disease, or smoking status. These results suggest that MGO levels fluctuate in progression of CRC and warrants further research into its underlying mechanisms and function in tumor biology.

The C-reactive protein-to-albumin ratio is a proven prognostic predictor of nasopharyngeal carcinoma. However, the role of the C-reactive protein-to-albumin ratio in other head and neck cancers remains unclear. This meta-analysis explored the prognostic value of the C-reactive protein-to-albumin ratio in head and neck cancers. A systematic search was conducted. Outcomes of interest included overall survival, disease-free survival, and distant metastasis–free survival. The hazard ratio with 95% confidence interval was pooled using a random-effects model. A total of 11 publications from the literature were included, allowing for the analysis of 7080 participants. Data pooling demonstrated that pretreatment C-reactive protein-to-albumin ratio had a hazard ratio of 1.88 (95% CI: 1.49−2.37, p < 0.001) for predicting overall survival, 1.91 (95% CI: 1.18−3.08, p = 0.002) for disease-free survival, and 1.46 (95% CI: 1.08−1.96, p = 0.001) for distant metastasis–free survival. Subgroup analysis showed that the C-reactive protein-to-albumin ratio is a significant prognostic marker for various head and neck cancers. An elevated pretreatment C-reactive protein-to-albumin ratio predicts a worse prognosis for patients with head and neck cancers. Therefore, the C-reactive protein-to-albumin ratio could serve as a potential prognostic biomarker facilitating treatment stratification.

Previous research has suggested an association between antidepressants use and clinical restless legs syndrome (RLS) in patients, but there has never been a single study investigating the risk of RLS in irritable bowel syndrome (IBS) patients treated with antidepressants. Hence, we aimed to explore the association between IBS and RLS and to examine the risk of RLS in IBS patients treated with antidepressants. With the use of the National Health Insurance Research Database of Taiwan, 27,437 adults aged ≥ 20 years with newly diagnosed IBS (ICD-9-CM Code 564.1) and gender- and age-matched 54,874 controls without IBS were enrolled between 2000 and 2012. All patients were followed-up until RLS diagnosis, withdrawal from the National Health Insurance program, or end of 2013. We used the Cox proportional hazards model to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of RLS. RLS was more prevalent in IBS patients than in the non-IBS group (7.57 versus 3.36 per 10,000 person-years), with an increased risk of RLS (adjusted HR [aHR], 1.91; 95% CI, 1.52-2.40). Multivariate Cox proportional hazards analysis identified older age (age, 51-65 years; aHR, 1.67; 95% CI, 1.09-2.56; and age > 65; aHR, 1.59; 95% CI, 1.02-2.48), hypothyroidism (aHR, 4.24; 95% CI, 1.92-9.37), CAD (aHR, 1.70; 95% CI, 1.17-2.48), and depression (aHR, 3.15; 95% CI, 2.14-4.64) as independent RLS risk factors in IBS patients. In addition, the male SSRIs users were associated with significantly higher risk of RLS (aHR, 3.05 95% CI, 1.34-6.92). Our study showed that the IBS group has higher risk of RLS. Moreover, SSRIs use may increase the risk of RLS in male IBS patients.

Extensive genetic studies have identified a large number of causal genetic variations in many human phenotypes; however, these could not completely explain heritability in complex diseases. Some researchers have proposed that the "missing heritability" may be attributable to gene-gene and gene-environment interactions. Because there are billions of potential interaction combinations, the statistical power of a single study is often ineffective in detecting these interactions. Meta-analysis is a common method of increasing detection power; however, accessing individual data could be difficult. This study presents a simple method that employs aggregated summary values from a "case" group to detect these specific interactions that based on rare disease and independence assumptions. However, these assumptions, particularly the rare disease assumption, may be violated in real situations; therefore, this study further investigated the robustness of our proposed method when it violates the assumptions. In conclusion, we observed that the rare disease assumption is relatively nonessential, whereas the independence assumption is an essential component. Because single nucleotide polymorphisms (SNPs) are often unrelated to environmental factors and SNPs on other chromosomes, researchers should use this method to investigate gene-gene and gene-environment interactions when they are unable to obtain detailed individual patient data.

BACKGROUND: Associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and chronic kidney disease (CKD) have been extensively studied, with most studies reporting that individuals with the D allele have a higher risk. Although some factors, such as ethnicity, may moderate the association between ACE I/D polymorphisms and CKD risk, gender-dependent effects on the CKD risk remain controversial. OBJECTIVES: This study investigated the gender-dependent effects of ACE I/D polymorphisms on CKD risk. DATA SOURCES: PubMed, the Cochrane library, and EMBASE were searched for studies published before January 2013. STUDY ELIGIBILITY CRITERIA PARTICIPANTS AND INTERVENTIONS: Cross-sectional surveys and case-control studies analyzing ACE I/D polymorphisms and CKD were included. They were required to match the following criteria: age >18 years, absence of rare diseases, and Asian or Caucasian ethnicity. STUDY APPRAISAL AND SYNTHESIS METHODS: The effect of carrying the D allele on CKD risk was assessed by meta-analysis and meta-regression using random-effects models. RESULTS: ETHNICITY [ODDS RATIO (OR): 1.24; 95% confidence interval (CI): 1.08-1.42] and hypertension (OR: 1.55; 95% CI: 1.04-2.32) had significant moderate effects on the association between ACE I/D polymorphisms and CKD risk, but they were not significant in the diabetic nephropathy subgroup. Males had higher OR for the association between ACE I/D polymorphisms and CKD risk than females in Asians but not Caucasians, regardless of adjustment for hypertension (p

Objective. In this study, we investigated whether RAAS gene single nucleotide polymorphisms (SNPs) and their interactions were associated with end-stage renal stage (ESRD). Methodology and Results. This was a case-control study for 647 ESRD cases and 644 controls. AGT (M235T (rs699) and T174M (rs4762)), AGTR1 (A1166C (rs5186) and C573T (rs5182)), ACE (I/D (rs1799752) and G2350A (rs4343)), and CYP11B2 C-344T (rs1799998) were genotyped and compared between cases and controls to identify SNPs associated with ESRD susceptibility. Multifactor dimensionality reduction (MDR) was used to identify gene-gene interactions. Several RAAS genes were associated with ESRD: AGT M235T, ACE I/D, ACE G2350A, and CYP11B2 C-344T. By MDR analysis, a three-locus model (ACE ID/ACE G2350A/CYP11B2 C-344T) of gene-gene interaction was the best for predicting ESRD risk, and its maximum testing accuracy was 56.08% and maximum cross-validation consistency was 9/10. ESRD risk was higher with the simultaneous occurrence of ACE I/D DD-ACE G2350A AA. AGT, ACE, and CYP11B2 gene polymorphisms are associated with ESRD. Conclusions. The gene-gene interaction effects of ACE I/D, ACE G2350A, and CYP11B2 C-344T polymorphisms are more important than individual factors for ESRD development among Han Chinese.

Inflammation induced by infectious and noninfectious triggers in the kidney may lead to end stage renal disease (ESRD). Toll-like receptor 9 (TLR-9) a receptor for CpG DNA is involved in activation of immune cells in renal disease and may contribute to chronic inflammatory disease progression through an interleukin-6 (IL-6) dependent pathway. Previous studies indicate that -1237T/C confers regulatory effects on TLR-9 transcription. To date the effect of TLR-9 polymorphisms on ESRD remains unknown. We performed a case-control study and genotyped 630 ESRD patients and 415 controls for -1237T/C, -1486T/C and 1635G/A by real-time PCR assays and assessed plasma concentration of IL-6 by ELISA. Haplotype association analysis was performed using the Haploview package. A luciferase reporter assay and real-time PCR were used to test the function of the -1237T/C promoter polymorphism. A significant association between -1237T/C in TLR-9 and ESRD was identified. The TCA, TTA and CCA haplotype of TLR-9 were associated with ESRD. ESRD patients carrying -1237TC had a higher mean plasma IL-6 level when compared with -1237TT. The TLR-9 transcriptional activity of the variant -1237CC allele is higher than the -1237TT allele. The results indicate that in a Han Chinese population the presence of the C allele of -1237T/C in the TLR-9 gene increases susceptibility towards development of ESRD. In vitro studies demonstrate that -1237T/C may be involved in the development of ESRD through transcriptional modulation of TLR-9.