Lipid metabolomic signature might predict subclinical atherosclerosis in patients with active rheumatoid arthritis.

OBJECTIVES: Although 1H-nuclear magnetic resonance (NMR)-based lipid/metabolomics has been used to detect atherosclerosis, data regarding lipid/metabolomic signature in rheumatoid arthritis (RA)-related atherosclerosis are scarce. We aimed to identify the distinct lipid/metabolomic profiling and develop a prediction score model for RA patients with subclinical atherosclerosis (SA). METHODS: Serum levels of lipid metabolites were determined using 1H-NMR-based lipid/metabolomics in 65 RA patients and 12 healthy controls (HCs). The occurrence of SA was defined as the presence of carotid plaques revealed in ultrasound images. RESULTS: Compared with HC, RA patients had significantly higher levels of phenylalanine and glycoprotein acetyls (GlycA) and lower levels of leucine and isoleucine. RA patients with SA had significantly higher levels of phenylalanine, creatinine, and glycolysis_total and lower levels of total lipid in HDL(HDL_L) than RA patients without SA. The Lasso logistic regression analysis revealed that age, creatinine, HDL_L, and glycolysis_total were significant predictors for the presence of SA. The prediction scoring algorithm was built as ( -0.657 + 0.011*Age + 0.004*Creatinine -0.120*HDL_L + 0.056*glycolysis-related measures), with AUC 0.90, sensitivity 83.3%, and specificity 87.2%. Serum phenylalanine levels were significantly decreased, and the levels of HDL_L and HDL_Particle were significantly increased in 20 RA patients, paralleling the decrease in disease activity score for 28-joints. CONCLUSIONS: With 1H-NMR-based lipid/metabolomics, distinct profiling of lipid metabolites was identified between RA patients and HC or between RA patients with and without SA. We further developed a scoring model based on lipid/metabolomics profiling for predicting RA-associated SA.

Long-term exposure to air pollution and risk of Sarcopenia in adult residents of Taiwan: a nationwide retrospective cohort study.

BACKGROUND: Sarcopenia is an age-related, multifactorial syndrome. Previous studies have shown that air pollutants are associated with inflammation and oxidative stress. However, the association between long-term exposure to air pollution and sarcopenia is not completely understood. METHODS: The Taiwan National Health Research Database (NHIRD) contains medical records of almost all Taiwanese residents. Daily air pollution data collected by the Taiwan Environmental Protection Agency was used to analyze concentrations of sulfur oxide (SO2), carbon monoxide (CO), nitrogen monoxide (NO), nitrogen dioxide (NO2), and particulate matter (PM2.5, PM10). The databases were merged according to the insurants' living area and the location of the air quality monitoring station. We categorized the pollutants into quartiles (Q1, Q2, Q3, and Q4). RESULTS: Our study population consisted of 286,044 patients, among whom 54.9% were female and 45.1% were male. Compared to Q1 levels of pollutants, Q4 levels of SO2 (adjusted hazard ratio [aHR] = 8.43; 95% confidence interval [CI] = 7.84, 9.07); CO (aHR = 3.03; 95%CI = 2.83, 3.25); NO (aHR = 3.47; 95%CI = 3.23, 3.73); NO2 (aHR = 3.72; 95%CI = 3.48, 3.98); PM2.5 (aHR = 21.9; 95% CI = 19.7, 24.5) and PM10 (aHR = 15.6; 95%CI = 14.1, 17.4) increased risk of sarcopenia. CONCLUSIONS: Our findings indicated a significantly increased risk of sarcopenia in both male and female residents exposed to high levels of air pollutants.

Epilepsy and Attention Deficit Hyperactivity Disorder: Connection, Chance, and Challenges.

Comorbidities are common in children with epilepsy, with nearly half of the patients having at least one comorbidity. Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder characterized by hyperactivity and inattentiveness level disproportional to the child's developmental stage. The burden of ADHD in children with epilepsy is high and can adversely affect the patients' clinical outcomes, psychosocial aspects, and quality of life. Several hypotheses were proposed to explain the high burden of ADHD in childhood epilepsy; the well-established bidirectional connection and shared genetic/non-genetic factors between epilepsy and comorbid ADHD largely rule out the possibility of a chance in this association. Stimulants are effective in children with comorbid ADHD, and the current body of evidence supports their safety within the approved dose. Nonetheless, safety data should be further studied in randomized, double-blinded, placebo-controlled trials. Comorbid ADHD is still under-recognized in clinical practice. Early identification and management of comorbid ADHD are crucial to optimize the prognosis and reduce the risk of adverse long-term neurodevelopmental outcomes. The identification of the shared genetic background of epilepsy and ADHD can open the gate for tailoring treatment options for these patients through precision medicine.

The Sizes and Composition of HDL-Cholesterol Are Significantly Associated with Inflammation in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using 1H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.

Administration of Bevacizumab and the Risk of Chronic Kidney Disease Development in Taiwan Residents: A Population-Based Retrospective Cohort Study.

Vascular endothelial growth factor (VEGF) plays a significant role as a pro-angiogenic and pro-permeability factor within the kidney. Bevacizumab is a pharmaceutical monoclonal anti-VEGF antibody that inhibits the growth of new blood vessels, which blocks blood supply and thereby restricts tumor growth. Thus, we conducted a nationwide study to explore the risk of chronic kidney disease (CKD) development in Taiwan residents after bevacizumab therapy. We drew data from the extensive National Health Insurance Research Database (NHIRD), which encompasses data from >99% of Taiwan's population from 1995 onwards. Individuals who received bevacizumab between 2012-2018 were identified as the bevacizumab cohort, with the index date set at the first usage. We randomly selected dates within the study period for the control group to serve as index dates. We excluded patients with a history of CKD prior to the index date or those <20 years old. In both cohorts, patients' propensity scores matched in a 1:1 ratio based on sex, age, index year, income, urbanization level, comorbidities, and medications. We found patients treated with bevacizumab had a significantly higher risk of contracting CKD than patients without bevacizumab (adjusted hazard ratio = 1.35, 95% confidence interval = 1.35-1.73). The risk of CKD was 1.35-fold higher in participants with bevacizumab treatment than those in the control group. These findings suggest that close monitoring of CKD development after bevacizumab administration is needed.

Dual-lumen power injectable peripherally inserted central catheters in allogeneic hematopoietic stem cell transplantation: A prospective observational study.

AIMS AND OBJECTIVES: To explore whether dual-lumen power injectable peripherally inserted central catheters (PICCs) could be effectively and safely applied in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and for serum cyclosporine level monitoring. BACKGROUND: Compared to conventional central venous access devices, PICC provides a feasible route not only for fluid infusion, but also for blood sample collection in patients undergoing oncological treatments. DESIGN: A prospective observational study was conducted according to the STROBE guidelines. METHODS: We prospectively evaluated the applications and complications of power injectable PICCs in 52 consecutive allo-HSCT recipients. We also compared the cyclosporine levels in 188 paired blood samples, simultaneously obtained via power injectable PICCs and percutaneous venous puncture, to investigate whether power injectable PICC is a feasible route for cyclosporine concentration monitoring in allo-HSCT. RESULTS: The median PICC placement duration was 29 days. The insertion-site blood oozing and central line-associated bloodstream infection rates were 36.5% (19/52) and 26.9% (14/52), respectively, indicating the feasibility of these PICCs for various applications in allo-HSCT. No power injectable PICC-related thrombotic adverse events were identified; 90.4% (47/52) of cases with power injectable PICC removal occurred because of lack of medical utility, suggesting that power injectable PICC-related complications were manageable. However, cyclosporine levels in samples obtained via these PICCs were significantly higher than those in samples obtained via percutaneous venous puncture (261.5 ± 139.2 vs. 232.4 ± 253.6 ng/ml; p = 0.019 [set 1]; 254.8 ± 89.3 vs. 225.1 ± 233.3 ng/ml; p<0.001 [set 2]; 283.6 ± 103.9 vs. 238.0 ± 254.7 ng/ml; p = 0.006 [set 3]; 291.0 ± 94.9 vs. 266.0 ± 274.7 ng/ml; p = 0.016 [set 4]). CONCLUSION: The power injectable PICC is a feasible venous access device for allo-HSCT. RELEVANCE TO CLINICAL PRACTICE: The dual-lumen power injectable PICCs provided a reliable access for blood sample collection, decreasing the number of blind percutaneous venous punctures in allo-HSCT. However, its application in cyclosporine level monitoring needs further investigation.

Lactoferrin Ameliorates Ovalbumin-Induced Asthma in Mice through Reducing Dendritic-Cell-Derived Th2 Cell Responses.

Asthma is a chronic respiratory disease with symptoms such as expiratory airflow narrowing and airway hyperresponsiveness (AHR). Millions of people suffer from asthma and are at risk of life-threatening conditions. Lactoferrin (LF) is a glycoprotein with multiple physiological functions, including antioxidant, anti-inflammatory, antimicrobial, and antitumoral activities. LF has been shown to function in immunoregulatory activities in ovalbumin (OVA)-induced delayed type hypersensitivity (DTH) in mice. Hence, the purpose of this study was to investigate the roles of LF in AHR and the functions of dendritic cells (DCs) and Th2-related responses in asthma. Twenty 8-week-old male BALB/c mice were divided into normal control (NC), ovalbumin (OVA)-sensitized, and OVA-sensitized with low dose of LF (100 mg/kg) or high dose of LF (300 mg/kg) treatment groups. The mice were challenged by intranasal instillation with 5% OVA on the 21st to 27th day after the start of the sensitization period. The AHR, cytokines in bronchoalveolar lavage fluid, and pulmonary histology of each mouse were measured. Serum OVA-specific IgE and IgG1 and OVA-specific splenocyte responses were further detected. The results showed that LF exhibited protective effects in ameliorating AHR, as well as lung inflammation and damage, in reducing the expression of Th2 cytokines and the secretion of allergen-specific antibodies, in influencing the functions of DCs, and in decreasing the level of Th2 immune responses in a BALB/c mouse model of OVA-induced allergic asthma. Importantly, we demonstrated that LF has practical application in reducing DC-induced Th2 cell responses in asthma. In conclusion, LF exhibits anti-inflammation and immunoregulation activities in OVA-induced allergic asthma. These results suggest that LF may act as a supplement to prevent asthma-induced lung injury and provide an additional agent for reducing asthma severity.

Long-term exposure to air pollution and the risk of developing sudden sensorineural hearing loss.

BACKGROUND: The association between exposure to air pollution and sudden sensorineural hearing loss (SSNHL) has not been extensively discussed in the literature. Therefore, we conducted this nationwide study to evaluate the risk of SSNHL in Taiwanese residents with exposure to air pollution. METHODS: We enrolled subjects aged older than 20 years with no history of SSNHL from 1998 to 2010, and followed up until developing SSNHL, withdrawn from the National Health Insurance program, and the end of the database (2011/12/31). The air quality data are managed by Taiwan Environmental Protection Administration. The annual concentrations of PM2.5, SO2, CO, NO, and NO2 from 1998 to 2010 were classified into the three levels according to tertiles. We calculated the annual average of pollutants from baseline until the end of the study, and classified into tertiles. The adjusted hazard ratio (aHR) was estimated by using the multivariate Cox proportional hazard model. RESULTS: When considered continuous air pollutants concentration, subjects who exposed with higher concentration of CO (aHR = 2.16, 95% CI 1.50-3.11), NO (aHR = 1.02, 95% CI 1.01-1.03), and NO2 (aHR = 1.02, 95% CI 1.01-1.04) developing significant higher risk of SSNHL. When classified air pollutants concentration into low, moderate and high level by tertiles, and selected low level as reference, patients exposed with moderate (aHR = 1.56, 95% CI 1.20-2.04) or high level (aHR = 1.33, 95% CI 1.01-1.75) of PM2.5 showed significant higher risk of developing SSNHL. CONCLUSION: This study indicated an increased risk of SSNHL in residents with long-term exposure to air pollution. Nevertheless, further experimental, and clinical studies are needed to validate the study findings.

Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice.

Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 µg/µL) injection at the same time point; and (ii) UCMSC exosome (1.2 µg/µL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.

Scrub typhus and depression: a nationwide cohort analysis.

BACKGROUND: Studies on the relationship between depression and scrub typhus are limited. We conducted a retrospective cohort study to investigate whether scrub typhus is a risk factor for depression. METHODS: Using Taiwan's National Health Insurance Research Database, this study investigated the incidence of depression, and its risk factors, in patients diagnosed with scrub typhus between 2000 and 2010. Scrub typhus patients who did not have a history of depression before the index date were enrolled. For each patient with scrub typhus, four controls without a history of scrub typhus and depression were randomly selected and frequency matched by sex, age, year of the index date, and comorbidities. The follow-up period was from the time of initial scrub typhus diagnosis to the date of diagnosis of depression, censoring, or December 31, 2010. Cox proportional hazards regression models were used to analyze the risk of depression according to sex, age, and comorbidities. RESULTS: The study comprised a 5238-patient scrub typhus group and a 20,952-patient non-scrub typhus group with similar sex and age distributions. During the follow-up period, the cumulative incidence of depression was higher in the scrub typhus than the non-scrub typhus group (log-rank test P < 0.001). In the scrub typhus group, 45 patients developed depression, yielding an incidence rate of 1.67 per 1000 person-years, and in the non-scrub typhus group, 117 patients developed depression, yielding an incidence rate of 1.08 per 1000 person-years. This yielded a crude hazard ratio (HR) of 1.55 (95% confidence interval [CI] 1.41-1.70) and adjusted HR (aHR) of 1.56 (95% CI 1.42-1.71). Compared with the non-scrub typhus group, the risk of depression in the scrub typhus group was higher in patients of both sexes (men: aHR = 1.46, 95% CI 1.29-1.64; women: aHR = 1.68, 95% CI 1.45-1.96), in patients aged younger than 65 (≤ 49 years: aHR = 1.95, 50-64 years: aHR = 1.73), and in patients without comorbidities (aHR = 2.06, 95% CI 1.85-2.29). CONCLUSIONS: The risk of depression was 1.56-fold higher in patients with scrub typhus than in the general population.

HBV infection increases the risk of macular degeneration: the roles of HBx-mediated sensitization of retinal pigment epithelial cells to UV and blue light irradiation.

BACKGROUND: Hepatitis B virus (HBV) infection is strongly associated with hepatocellular carcinoma due to the main pathogenic X protein of HBV (HBx). Whether HBV infection and the HBx protein could result in macular degeneration (MD) is not known. The aim of this study is to assess the association and underlying mechanisms between HBV infection and MD. METHODS: The National Health Research Institutes in Taiwan built a large database, the National Health Insurance Research Database (NHIRD), which includes the claims data from the Taiwan National Health Insurance (NHI) program. The Taiwan NHI is a single-payer, compulsory health insurance program for Taiwan citizens. The data for the present study were derived from the Longitudinal Health Insurance Database, which contains the claims data of 1 million insured people within the NHIRD, including beneficiary registration, inpatient and outpatient files, drug use, and other medical services. In this study, we first investigated the association of HBV infection and the risk of MD by a population-based cohorts study enrolling 39,796 HBV-infected patients and 159,184 non-HBV-infected patients. RESULTS: After adjustment of age, sex, and comorbidities, the risk of MD was significantly higher in the HBV-infected cohort than in the non-HBV-infected cohort (adjusted HR = 1.31; 95% CI = 1.17-1.46). In vitro, we provided evidence to demonstrate that overexpression of HBx in the human retinal pigment epithelial (RPE) cell line, ARPE19, significantly reduced cell viability and clonogenic survival upon UV and blue light irradiation. By gene microarray analysis, we further showed that almost all genes in DNA repair pathways including base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination were significantly down-regulated in the UV-induced cell death of HBx-transfected ARPE19 cells. CONCLUSIONS: The HBx protein may sensitize RPE cells to UV and blue light irradiation and increase the risk of HBV-infection-associated MD through down-regulation of multiple DNA repair pathways.

Association of viral hepatitis and bipolar disorder: a nationwide population-based study.

BACKGROUND: Bipolar disorder (BD), a type of psychiatric mood disorder, is manifested by chronic and recurrent mood fluctuations. This study aims to determine whether hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a risk factor for BD. METHODS: A total of 48,215 patients with newly diagnosed viral hepatitis from 2000 to 2010 were identified and frequency-matched with 192,860 people without hepatitis. Both groups were followed until diagnosis with BD, withdrawal from the national health insurance program, or the end of 2011. Patients with viral hepatitis were grouped into 3 cohorts: HBV infection, HCV infection, and HBV/HCV coinfection. The association between viral hepatitis and BD were examined using Cox proportional hazards regression models. RESULTS: The incidence of BD was higher in HBV/HCV coinfection than in the control group, with an adjusted hazard ratio of 2.16 (95% confidence interval 1.06-4.41) when adjusted for sex, age, and comorbidity. After further adjustment, we noted that an age more than 65 years and female may be associated with an increased risk of BD in patients with chronic hepatitis B and C. CONCLUSION: Viral hepatitis may be associated with increased risk of subsequent BD.

Age-related hearing loss and dementia: a 10-year national population-based study.

Age-related hearing loss (ARHL) is postulated to affect dementia. Our study aims to investigate the relationship between ARHL and the prevalence, and 10-year incidence of dementia in the Taiwan National Health Insurance Research Database (NHIRD). We selected patients diagnosed with ARHL from the NHIRD. A comparison cohort comprising of patients without ARHL was frequency-matched by age, sex, and co-morbidities, and the occurrence of dementia was evaluated in both cohorts. The ARHL cohort consisted of 4108 patients with ARHL and the control cohort consisted of 4013 frequency-matched patients without ARHL. The incidence of dementia [hazard ratio (HR), 1.30; 95% confidence interval (CI 1.14-1.49); P = 0.002] was higher among ARHL patients. Cox models showed that being female (HR, 1.34; 95% CI 1.07-1.68), as well as having co-morbidities, including chronic liver disease and cirrhosis, rheumatoid arthritis, hypertension, diabetes mellitus, stroke, head injury, chronic kidney disease, coronary artery disease, alcohol abuse/dependence, and tobacco abuse/dependence (HR, 1.27; 95% CI 1.11-1.45), were independent risk factors for dementia in ARHL patients. We found ARHL may be one of the early characteristics of dementia, and patients with hearing loss were at a higher risk of subsequent dementia. Clinicians should be more sensitive to dementia symptoms within the first 2 years following ARHL diagnosis. Further clinical studies of the relationship between dementia and ARHL may be necessary.

Outcome and late effects among acute myeloid leukemia survivors: a nationwide population-based study.

BACKGROUND: Understanding of pathogenesis and treatment for acute myeloid leukemia (AML) is growing. However, studies regarding the outcomes and late effects among AML survivors are relatively limited. METHODS: This nationwide population-based study used medical records from the Taiwanese National Health Insurance Research Database. A total of 3356 AML patients diagnosed from 2000 to 2008 were analyzed. The physiological and psychological morbidities in AML survivors were compared to those identified from a normal population. This study also compared late effects among AML survivors treated by intensive chemotherapy alone and allogeneic hematopoietic stem cell transplantation (allo-HSCT). RESULTS: The incidence of AML in Taiwan has increased from 1.07 per 100,000 persons in 2000 to 2.17 per 100,000 persons in 2008 (p < 0.0001). With the median overall survival (OS) time of 0.98 years, 25.0 % of AML patients in this study cohort received best supportive care alone. Compared to the normal population, AML survivors had higher rates of hypertension (hazard ratio [HR] 1.69; 95 % confidence interval [CI] 1.18-2.42; p < 0.01), cardiovascular disease (HR 2.53; 95 % CI 1.39-4.61; p < 0.01), diabetes (HR 2.27; 95 % CI 1.48-3.48; p < 0.001), and psychological disorders (HR 1.45; 95 % CI 1.04-2.04; p < 0.05). Although patients undergoing allo-HSCT had a better OS than did patients treated with intensive chemotherapy alone (median not reached vs. 1.53 years; p < 0.0001), diabetes was found more often among allo-HSCT recipients than among patients receiving intensive chemotherapy only (HR 2.93; 95 % CI 1.21-7.08; p < 0.05). CONCLUSION: Regular physical and psychological surveillance of AML survivors is needed especially for those receiving allo-HSCT.

Increased risk of fracture in patients with bipolar disorder: a nationwide cohort study.

OBJECTIVES: Bipolar disorder (BD) is a systemic inflammatory disease, and disrupted bone metabolism due to the inflammatory process can cause fracture. Despite evidence of an association between lower bone mineral density and an increased risk of fracture among patients with depression, schizophrenia, and anorexia nervosa, whether BD is a risk factor for subsequent fracture is unknown. To determine the association between BD and fracture and to examine the risk factors for fracture among patients with BD. METHODS: In this study, we enrolled patients diagnosed with BD from the Taiwan National Health Insurance Research Database. Patients newly diagnosed with BD (ICD-9-CM 296) from 2001 to 2008 were included in the BD cohort, and the date of the initial diagnosis of BD was used as the index date. The comparison cohort, comprising participants without BD, was frequency matched to the BD cohort by age, sex, and index year, and the occurrence of fracture was evaluated in both cohorts. RESULTS: The BD and comparison cohorts were comprised of 47,271 patients with BD and 1,89,084 frequency-matched participants without BD, respectively. The incidence of fracture was higher among patients with BD than among the controls. Cox models showed that BD was an independent risk factor for fracture irrespective of comorbidities [hazard ratio (HR) = 1.79, 95 % confidence interval (CI) = 1.73-1.84, p < .001]. CONCLUSION: Our study showed that patients with BD have a higher risk of subsequent fracture. Additional prospective clinical studies investigating the relationship between BD and fracture are warranted.

Thalassemia Phenotypes and Genotypes in Taiwan: A Retrospective Study Based on Thalassemia Screening of Young Men for Military Conscription.

Prenatal thalassemia studies from Taiwan show that one-third of fetuses with genetic abnormalities have ß-thalassemia major (ß-TM). However, the phenotypes and genotypes of adult thalassemia warrant further investigation. From September 2006 to April 2014, 741 male candidates drafted for military service with mean corpuscular volume (MCV) <80 fL and serum ferritin >20 µg/L were analyzed. The results showed that the detection rates of α- and ß-thalassemia (α- an ß-thal) were 50.20% (372/741) and 49.12% (364/741), respectively. Only five patients (0.67%) were diagnosed with both α- and ß-thal. The - -(SEA)/αα mutation was found in 76.88% (286/372) of α-thal patients. Heterozygous mutations in IVS-II-654 (C > T) and codons 41/42 (-TCTT) accounted for 55.77% (203/364) of ß-thal cases. The leukocyte counts for α- and ß-thal were 6241.74 ± 1552.99 and 6622.87 ± 1814.41 × 10(9)/L, respectively (p = 0.007). The α-thal patients had lower red blood cell (RBC) mass (5.85 ± 0.44 × 10(12)/L vs. 6.09 ± 0.45 × 10(12)/L; p < 0.001) and higher hemoglobin (Hb) (12.82 ± 0.72 vs. 12.35 ± 0.71 g/dL; p < 0.001) than ß-thal patients. Mean serum ferritin values were 169.67 and 241.36 µg/L, respectively, in α- and ß-thal patients (p < 0.001), indicating more profound ineffective erythropoiesis in ß-thal. Only four of the 741 patients underwent further hematological follow-up. Our study suggests that iron overload might be a potential problem in ß-thal patients; therefore, regular follow-up is highly recommended.

Palonosetron versus first-generation 5-hydroxytryptamine type 3 receptor antagonists for emesis prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation.

First-generation 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists (RAs) are currently the standard of care for prophylaxis against allo-HSCT-induced emesis. However, the efficacy of this combination in allo-HSCT recipients is not entirely satisfying. We sought to compare the efficacy of first-generation 5-HT3 RAs with that of second-generation 5-HT3 RAs in emesis prevention in allo-HSCT recipients. A total of 51 consecutive patients undergoing allo-HSCT for various hematological diseases in our institution were retrospectively reviewed. Patients who received daily first-generation 5-HT3 RAs, and 60-h palonosetron for emesis prophylaxis were stratified into the standard (n = 23) and palonosetron (n = 28) groups, respectively. Emesis severity and rescue therapy requirements in patients between these two groups were compared. Our results showed patients in standard and palonosetron groups had comparable severity of both acute and delayed emesis. However, 52.2 % of the patients in the standard group required rescue therapy, compared to only 21.4 % of the patients in the palonosetron group (p = 0.046). Subgroup analysis showed rescue therapy for acute emesis was required by 26.1 % of the patients in the standard group and by only 3.6 % of the patients in the palonosetron group (p = 0.037). In conclusion, palonosetron and first-generation 5-HT3 RAs were at least equally effective in emesis prophylaxis for allo-HSCT recipients. Patients receiving palonosetron, especially for acute emesis, required rescue therapy less frequently than those receiving first-generation 5-HT3 RAs.

Intravitreal ranibizumab injection is associated with an increased risk of chronic kidney disease: a population-based study in Taiwan.

Systemic vascular endothelial growth factor (VEGF) blockade has been the top adjunctive chemotherapy since 1990. Anti-VEGF therapy has also been associated with worsened renal function in some patients. However, the association between patient outcomes and use of intravitreal VEGF inhibitors remains controversial. Thus, it is necessary to determine the action mechanism and long-term renal effects of ranibizumab. The National Health Insurance Research Database (NHIRD) is one of the largest global databases that are extensively used for epidemiological research. NHIRD contains the medical information of all insureds, such as inpatient, outpatient, emergency, and traditional Chinese medicine records. We selected subjects aged ≥ 20 years who recently administered ranibizumab for the ranibizumab cohort. Non-ranibizumab cohort consisted of subjects who did not receive ranibizumab, and the index date was a random date between 2008 and 2018. We excluded subjects with missing sex and age records and those in which the date of primary outcome was before the index date. The two cohorts were matched via 1:1 propensity score matching based on sex, age, index year, hypertension, diabetes mellitus, hyperlipidemia, stroke, coronary artery disease, alcoholism, chronic obstructive pulmonary disease, and age-related macular degeneration, retinal vein occlusion, and diabetic macular edema. Medical confounders were angiotensin I-converting enzyme inhibitors, statins, corticosteroids, VEGF inhibitors including bevacizumab and aflibercept, lithium, amphotericin B, adefovir, NSAIDS, cisplatin, and calcineurin inhibitors. Among 48,248 participants aged ≥ 20 years, 24,136 (50%) received ranibizumab (13,565 male [56.20%] and 10,571 female [43.80%]). Moreover, 24,136 participants who did not receive ranibizumab were matched by age, sex, comorbidities, and medications. Subjects who received ranibizumab exhibited a significantly higher risk of CKD than those who did not receive ranibizumab (adjusted hazard ratio = 1.88, 95% CI = 1.79-1.96). Our findings revealed that exposure to intravitreal ranibizumab is an independent risk factor for CKD. Therefore, physicians and ophthalmologists should make the patients aware of such a correlation to increase patient safety and decrease the CKD burden.

Association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and macular degeneration in patients with diabetes: a nationwide population-based study in Taiwan.

AIMS: Evidence showed that SGLT2 inhibitors have greater protective effects against retinal diseases compared to other hypoglycemic agents. Thus, we explore the association between SGLT2 inhibitor usage and macular degeneration (MD) in Taiwanese patients with diabetes. METHODS: The National Health Insurance (NHI) program's claim data are released as the National Health Insurance Research Database (NHIRD). This database covers more than 99% of the residents in Taiwan. We included data on patients who were newly diagnosed with type 2 diabetes mellitus (ICD-9-CM: 250, exclude 250.1x; ICD-10-CM: E11), with an age at diagnosis of over 20 years as our study population. Patients who received (sodium-glucose cotransporter 2 inhibitor) SGLT2i (ATC code: A10BK) over 90 days in 2016-2019 were defined as the SGLT2i cohort. Conversely, patients who did never received SGLT2i were defined as the non-SGLT2i cohort. The exclusion criteria were having MD before the index date, receiving SGLT2i within 1-89 days, and missing data on sex, age, or days of SGLT2i usage. Two cohorts were matched by 1:1 propensity score matching, which was based on age, sex, payroll bracket grade, urbanization, comorbidities, and medications. RESULTS: Compared to non-SGLT2i cohort, patients who received SGLT2i had a significantly lower risk of MD (adjusted hazard ratio = 0.70, 95%CI = 0.66-0.75). CONCLUSIONS: We found that SGLT2is has a strong protective effect against MD in patients with diabetes. SGLT2is may have benefits beyond glycemic control in patients with DR. However, additional clinical and experimental studies are required.

Effect of nocturia in patients with different severity of obstructive sleep apnea on polysomnography: A retrospective observational study.

Objective: Obstructive sleep apnea (OSA) is one of the etiologies of nocturia. We analyzed polysomnography (PSG) results to determine correlated factors related to nocturia in OSA patients with different severity. Methods: Patients with suspected OSA were examined using PSG. They were divided into two groups based on the presence of nocturia. Nocturia was defined as a patient who needed to void at least once. Apnea-hypopnea index (AHI) was employed to classify patients according to degrees of severity: AHI<5 events/h, 5 events/h≤AHI<15 events/h, 15 events/h≤AHI<30 events/h, and AHI≥30 events/h, defined as normal, mild OSA, moderate OSA, and severe OSA, respectively. Demographic variables, PSG parameters, International Prostate Symptom Scores (IPSSs), and quality of life scores due to urinary symptoms were analyzed. Results: In total 140 patients, 114 patients had OSA (48 had mild OSA; 34 had moderate OSA; and 32 had severe OSA) and 107 patients had nocturia. The total IPSS was significantly higher in nocturia patients in all groups except the group of severe OSA patients. With the increasing severity of OSA, more correlated factors related to nocturia were determined. In mild OSA patients, nocturia related to increased age (p=0.025), minimum arterial blood oxygenation saturation (p=0.046), and decreased AHI of non-rapid eye movement (p=0.047), AHI of total sleep time (p=0.010), and desaturation index (p=0.012). In moderate OSA patients, nocturia related to increased age (p<0.001), awake time (p=0.025), stage 1 sleep (p=0.033), and sleep latency (p=0.033), and decreased height (p=0.044), weight (p=0.025), and sleep efficiency (p=0.003). In severe OSA patients, nocturia related to increased weight (p=0.011), body mass index (p=0.009), awake time (p=0.008), stage 1 sleep (p=0.040), arousal number (p=0.030), arousal index (p=0.013), periodic limb movement number (p=0.013), and periodic limb movement index (p=0.004), and decreased baseline arterial blood oxygenation saturation (p=0.046). Conclusion: Our study revealed that there were more correlated factors related to nocturia with increasing severity of OSA. This study helps in clinical education and treatment for OSA patients with different severity.