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Background: The transmission and fatal risk of severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease first discovered in China in 2009, still needed further quantification. This research aimed to analyze the SFTS clusters and assess the transmission and mortality risk for SFTS. Methods: Both epidemiological investigation and case reports regarding SFTS clusters in China during 2011–2021 were obtained from the Public Health Emergency Information Management System of the Chinese Center for Disease Control and Prevention Information System. The transmission risk was evaluated by using the secondary attack rate (SAR) and relative risk (RR). Mortality risk factors were analyzed using a logistic regression model. Results: There were 35 SFTS clusters during 2011–2021 involving 118 patients with a fatality rate of 22.0%. The number of clusters annually increased seasonally from April to September. The clusters mainly occurred in Anhui (16 clusters) and Shandong provinces (8 clusters). The SAR through contact with blood or bloody fluids was much higher than that through contact with non-bloody fluids (50.6% vs 3.0%; χ2 = 210.97, P < 0.05), with an RR of 16.61 [95% confidence interval (CI): 10.23–26.97]. There was a statistically significant difference in the SAR between exposure to the blood of a deceased person during burial preparation and exposure to the living patients' blood (66.7% vs 34.5%; χ2 = 6.40, P < 0.05), with an RR of 1.93 (95% CI: 1.11–3.37). The mortality risk factors were a long interval from onset to diagnosis [odds ratio (OR) = 1.385), 95% CI: 1.083–1.772, P = 0.009) and advanced age (OR: 1.095, 95% CI: 1.031–1.163, P = 0.01). Conclusions: The SFTS clusters showed a high mortality rate and resulted in a high SAR. Contact with a bleeding corpse was associated with a higher infection risk, compared with contacting the blood from living patients. It is important to promote early detection and appropriate case management of patients with SFTS, as well as improved handling of their corpses, to prevent further transmission and mortality. [ABSTRACT FROM AUTHOR]

Background: Despite the continued improvement in the surgical techniques during primary total knee arthroplasty (TKA), literatures indicate that up to 10 to 20% patients are not satisfied with their outcomes. Psychological factors in this dissatisfaction are yet to be clearly identified. The aim of this study is to develop a method to assess whether the patient's current mental state is suitable enough to accept a TKA surgery. Methods: Preoperative demographic and clinical data of 532 patients who underwent TKA were prospectively obtained from January 2012 until December 2016. We recorded the scores evaluated by SF-36 questionnaire and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) preoperatively and 1 year postoperatively. Preoperative Life Satisfaction Rating (LSR) is emphatically evaluated. Results: Poor preoperative score of LSR was a significant predictor of dissatisfaction after TKA. Patients with low LSR reported significant pain and stiffness, although there was no remarkable effect on functionality of the replaced joint. The results also showed that age and BMI were not strong predictors of satisfaction in TKA. Conclusion: Our outcomes can help clinicians evaluate whether a patient's current mental status is favorable for TKA. If patients have extreme low scores of LSR (less than 10), a psychological intervention should be recommended for better satisfaction following a TKA surgery. This would also allow surgeons to individually assess the risks and benefits of surgery. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is one of the worst cancers with bad prognosis despite systemic chemotherapy and radiotherapy after surgery.Methods: In this study, 71 patients with GBM were enrolled and randomly assigned to two groups: Receiving radiotherapy with concomitant and adjuvant temozolomide (TMZ) (TMZ, standard therapy) after surgery, or receiving radiotherapy with concomitant and adjuvant local delivery of nimustine (ACNU) rendezvousing with oral TMZ (rendezvous therapy). In the follow-up of all patients and the progression-free survival (PFS), overall survival (OS), Karnofsky performance score (KPS) and toxicities were recorded.Results: For the whole cohort, the median OS was 18.0 months, and the median PFS was 7.8 months. A significantly longer OS was observed in patients received rendezvous therapy than those who receiving standard therapy (18.5 months vs. 16.0 months; P = 0.014), as well as PFS (8.8 months vs. 7.0 months; P = 0.008). The KPS ≥70 rates were 81.8%, 40.9%, 20.5% in 1, 2, and 3 years for the rendezvous therapy group, significantly superior to standard therapy group. The most common toxicities were tolerable gastrointestinal reaction, liver dysfunction, and hematological toxicities, which were relieved with symptomatic treatment. Grade 3 or 4 toxicity was documented in 8 (18.3%) patients in rendezvous therapy group, while it was observed in 6 (22.2%) patients in standard therapy group during whole treatment process.Conclusions: Compared to standard therapy, the antitumor effects of rendezvous therapy were more effective in GBM patients without increasing the toxicities. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the value of pirarubicin (THP) photosensitizer fluorescence cystoscopy for the early diagnosis of bladder cancer. From January 2012 to June 2015, 25 patients with painless gross hematuria, were injected with THP 15 min prior to surgery and subsequently underwent fluorescence cystoscopy examination. Locations of tumors were recorded and biopsies were performed (total of 109 biopsies) under white and fluorescence light guidance. Biopsies were conducted at the THP-positive and -negative areas under white light and THP-positive areas under fluorescence light. Positive rate of bladder tumor tissue at the THP-positive areas detected under fluorescence light was 92.86%. The sensitivity and specificity were 100 and 96.15%, respectively. The positive rate of tumor tissue at the THP-positive areas detected under white light was 70.97%. The sensitivity and specificity were 100 and 84.74%, respectively. Fifty biopsies taken at the THP-negative areas under white light were found to be non-urothelial carcinoma tumor lesions. Thus, applying (THP) photosensitizer fluorescence cystoscopy for early-period bladder cancer diagnosis is safe, effective and practical. It showed a high degree of specificity and a low rate of false positives. It was a convenient visual diagnostic method for the early detection of non-muscular invasive bladder cancer. [ABSTRACT FROM AUTHOR]

Bleomycin (BLM) is used clinically in combination with a number of other agents for the treatment of several types of tumours. Members of the BLM family of drugs include zorbamycin (ZBM), phleomycin D1, BLM A2 and BLM B2. By manipulating the BLM biosynthetic machinery, we have produced two new BLM analogues, BLM Z and 6′-deoxy-BLM Z, with the latter exhibiting significantly improved DNA cleavage activity. Here we determined the DNA sequence specificity of BLM Z, 6′-deoxy-BLM Z and ZBM, in comparison with BLM, with high precision using purified plasmid DNA and our recently developed technique. It was found that ZBM had a different DNA sequence specificity compared with BLM and the BLM analogues. While BLM and the BLM analogues showed a similar DNA sequence specificity, with TGTA sequences as the main site of cleavage, ZBM exhibited a distinct DNA sequence specificity, with both TGTA and TGTG as the predominant cleavage sites. These differences in DNA sequence specificity are discussed in relation to the structures of ZBM, BLM and the BLM analogues. Our findings support the strategy of manipulating the BLM biosynthetic machinery for the production of novel BLM analogues, difficult to prepare by total synthesis; some of which could have beneficial cancer chemotherapeutic properties. [ABSTRACT FROM AUTHOR]

Crohn’s disease (CD) is an idiopathic inflammatory bowel disease involving the small and/or large intestine. More than 50% of Western CD patients and up to 88% of Asian CD patients may have small intestinal involvement. Video capsule endoscopy (VCE) has a higher diagnostic yield than small bowel barium radiography and computed tomography enterography for the detection of small intestinal involvement of CD. VCE also provides diagnostic yields comparable to magnetic resonance- (MR-) based enterography or enteroclysis and may have several advantages over MR-based tests for the detection of early small intestinal lesions. Several studies have suggested the use of VCE-based disease activity scoring systems to evaluate small intestinal mucosal disease activity, although their clinical relevance needs to be further studied. A possible indication for VCE is recurrence monitoring after complete surgical excision of CD-involved segments but its usefulness and efficacy compared with conventional endoscopy should be evaluated. The capsule retention rate ranges from 0 to 5.4% in suspected CD patients and from 0 to 13.2% in established CD patients. If VCE is necessary, significant small bowel stricture should be ruled out before VCE by performing a patency capsule study and/or small bowel radiological study in suspected or established CD patients. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the role of preoperative cardiac computed tomography (CT) for adults with congenital cardiac septal defect (CSD). Methods: Sixty-five consecutive patients who underwent preoperative CT and surgery for CSD were included. The diagnostic accuracy of CT and the concordance rate of the subtype classification of CSD were evaluated using surgical findings as the reference standard. Sixty-five patients without CSD who underwent cardiac valve surgery were used as a control group. An incremental value of CT over echocardiography was described retrospectively. Results: Sensitivity and specificity of CT for diagnosis of CSD were 95 % and 100 %, respectively. The concordance rate of subtype classification was 91 % in CT and 92 % in echocardiography. The maximum size of the defect measured by CT correlated well with surgical measurement ( r = 0.82), and the limit of agreement was -0.9 ± 7.42 mm. In comparison with echocardiography, CT was able to detect combined abnormalities in three cases, and exclusively provided correct subtype classification or clarified suspected abnormal findings found on echocardiography in seven cases. Conclusions: Cardiac CT can accurately demonstrates CSD in preoperative adult patients. CT may have an incremental role in preoperative planning, particularly in those with more complex anatomy. Key Points: • Cardiac CT can demonstrate cardiac septal defect accurately in preoperative planning. • Cardiac CT can demonstrate combined abnormalities of cardiac septal defect. • Cardiac CT may have an incremental role over echocardiography in complex anatomy. [ABSTRACT FROM AUTHOR]

Objective. To establish and validate a nomogram to predict the overall survival (OS) and cancer-specific survival (CSS) in patients with nasopharyngeal carcinoma (NPC) receiving radiotherapy by integrating multiple independent prognostic factors. Materials and Methods. Data from 5663 patients with NPC who received definite radiotherapy between 2004 and 2018 were included and divided into training and validation cohorts. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors of patients with NPC after radiotherapy. Thereafter, the predictive accuracy of the nomogram model was evaluated. Results. Age, race, marital status, pathological type, tumor size, T stage, N stage, M stage, American Joint Committee on Cancer stage, and chemotherapy were independent factors affecting the prognosis of patients with NPC receiving radiotherapy. Nomograms with a concordance index of 0.726 (95% confidence interval (CI): 0.675–0.777) and 0.732 (95% CI: 0.680–0.785) were able to predict OS and CSS, respectively. The area under the curve showed excellent predictive performance. Additionally, the calibration curve indicated that the predicted survival rate was consistent with the actual survival rate, and the decision curve indicated its clinical value. The established risk stratification system was able to accurately stratify patients receiving radiotherapy for NPC into three risk subgroups with significant differences in prognosis (P < 0.05). Conclusions. The constructed nomogram had good prognostic performance and could be used as an effective tool to evaluate the prognosis of patients with NPC after radiotherapy. This nomogram could be further used to guide clinical decisions and personalized treatment plans. [ABSTRACT FROM AUTHOR]

Objective. Constipation in patients with mild spinal cord disease is not well investigated yet. We aimed to investigate anorectal function and the effect of biofeedback therapy in constipated patients with mild spinal cord diseases. Material and methods. A total of 14 constipated patients with myelopathy and 32 with radiculopathy were enrolled retrospectively. All patients were able to walk independently. The control group comprised of 100 constipated patients without any neurologic problem. Colonic transit time and the presence of dyssynergia were assessed before biofeedback therapy. All patients answered structured questionnaires on constipation, before and after biofeedback therapy. Results. The mean rectosigmoid colonic transit time of the myelopathy group was significantly delayed (myelopathy, 18.6 ± 14.6 h; radiculopathy, 12.8 ± 11.9 h; control, 9.6 ± 11.2 h; p = 0.032). Delay in total colonic transit time was more frequent in the myelopathy group (myelopathy, 57.1%; radiculopathy, 23.3%; control, 18.5%; p = 0.004). On anorectal manometry, the squeezing pressure of the anal sphincter was decreased in the myelopathy group (myelopathy, 132.3 ± 73.3 mmHg; radiculopathy, 179.9 ± 86.1 mmHg; control 200.4 ± 82.4 mmHg; p < 0.05). The success rate of biofeedback therapy was lower in the myelopathy group (28.6% for myelopathy vs. 62.0% for control group; p = 0.034). The response rate to biofeedback therapy was similar between radiculopathy and control group (62.5% for radiculopathy vs. 62.0% for control group; p = 1.000). Conclusions. In constipation associated with mild myelopathy, delayed colonic transit and dyssynergic defecation were major pathophysiologic abnormalities and biofeedback was less effective compared with control group. However, in the radiculopathy group, biofeedback was as effective as in the control group. [ABSTRACT FROM AUTHOR]

Abstract: Idiopathic normal pressure hydrocephalus (iNPH) is a reversible dementia characterized by gait disturbance, incontinence and dementia. This study investigates the neuropsychological characteristics and changes of regional cerebral blood flow (rCBF) in patients with iNPH. Ten patients who met the criteria of probable iNPH and 13 normal control subjects were evaluated. The general cognitive function and detailed neuropsychological functions were measured by K-MMSE and comprehensive neuropsychological battery. Tc-99m-ethyl cysteinate dimmer (Tc-99m-ECD) single photon emission computed tomography (SPECT) was performed to measure the rCBF and statistical parametric mapping (SPM) and statistical probabilistic brain anatomic map (SPAM) was applied to the objective analysis of SPECT data. On the neuropsychological examination, all the patients showed abnormality in memory, psychomotor speed and frontal executive function. SPM analysis of SPECT images revealed that rCBF in bilateral thalami, right prefrontal area, bilateral anterior and posterior cingulate gyri, right caudate nucleus, and left parahippocampal gyrus was significantly decreased in patients with iNPH compared to normal controls (uncorrected P<0.005). In SPAM analysis, rCBF reduction was observed in bilateral prefrontal area, anterior, posterior cingulate gyri and caudate nuclei. We have found that rCBF changes occurred predominantly in prefrontal and subcortical areas, the changes were associated with frontal subcortical circuit, and the affected frontal subcortical circuit may contribute to the cognitive decline seen in the iNPH patients. The reduction of rCBF and clinical cognitive impairment are closely connected in patients with iNPH. [Copyright &y& Elsevier]

Background: Universal Zero-Markup Drug Policy (UZMDP) mandates no price mark-ups on any drug dispensed by a healthcare institution, and covers the medicines not included in the China’s National Essential Medicine System. Five tertiary hospitals in Beijing, China implemented UZMDP in 2012. Its impacts on these hospitals are unknown. We described the effects of UZMDP on a participating hospital, Jishuitan Hospital, Beijing, China (JST). Methods: This retrospective longitudinal study examined the hospital-level data of JST and city-level data of tertiary hospitals of Beijing, China (BJT) 2009–2015. Rank-sum tests and join-point regression analyses were used to assess absolute changes and differences in trends, respectively. Results: In absolute terms, after the UZDMP implementation, there were increased annual patient-visits and decreased ratios of medicine-to-healthcare-charges (RMOH) in JST outpatient and inpatient services; however, in outpatient service, physician work-days decreased and physician-workload and inflation-adjusted per-visit healthcare charges increased, while the inpatient physician work-days increased and inpatient mortality-rate reduced. Interestingly, the decreasing trend in inpatient mortality-rate was neutralized after UZDMP implementation. Compared with BJT and under influence of UZDMP, JST outpatient and inpatient services both had increasing trends in annual patient-visits (annual percentage changes[APC] = 8.1% and 6.5%, respectively) and decreasing trends in RMOH (APC = -4.3% and -5.4%, respectively), while JST outpatient services had increasing trend in inflation-adjusted per-visit healthcare charges (APC = 3.4%) and JST inpatient service had decreasing trend in inflation-adjusted per-visit medicine-charges (APC = -5.2%). Conclusion: Implementation of UZMDP seems to increase annual patient-visits, reduce RMOH and have different impacts on outpatient and inpatient services in a Chinese urban tertiary hospital. [ABSTRACT FROM AUTHOR]

Background: Hypermethylation of DLX4 (distal-less homeobox 4) has been disclosed in a variety of cancers. Our work was aimed to examine the pattern of DLX4 methylation and further investigate its clinical relevance in patients with myelodysplastic syndrome (MDS). Methods: Real-time quantitative methylation-specific PCR and bisulfite sequencing PCR were carried out to detect the level of DLX4 methylation. Clinical significance of DLX4 methylation was analyzed between the DLX4 hypermethylated and non-hypermethylated patients. Results: DLX4 was significantly hypermethylated in MDS patients than controls (p<0.001). No significant differences were observed between the hypermethylated and non-hypermethylated MDS patients in white blood cells, platelets, age, WHO classifications, FAB classifications, IPSS risks, and common gene mutations (p>0.05). However, DLX4 hypermethylated patients tended to have higher hemoglobin (HB) than DLX4 non-hypermethylated patients (p=0.079). Moreover, there was a trend that male patients, poor karyotype patients, and IPSS Int-2/High patients had a higher frequency of DLX4 hypermethylation (p=0.067, 0.065, and 0.068). DLX4 hypermethylated patients had significantly shorter overall survival than DLX4 non-hypermethylated patients (p=0.004). Multivariate analysis confirmed the prognostic value of DLX4 methylation in MDS patients (p<0.001). Conclusions: Our study indicated that DLX4 hypermethylation was a frequent event and acted as an independent prognostic biomarker in de novo MDS patients. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This study aimed to determine whether regional cerebral blood flow (rCBF) is abnormal in patients who have Transient Global Amnesia (TGA). Methods: We obtained noninvasive rCBF measurements using Tc-99m-ethyl cysteinate diamer Single Photon Emission Computed Tomography (SPECT) in 7 patients diagnosed with TGA within 4 days of onset of the amnestic episode while the patients were still symptomatic and in 17 age-matched healthy control subjects. We assessed memory functioning using the Hopkins''s Verbal Learning Test (HVLT) and Statistical Parametric Mapping to compare rCBF across diagnostic groups. Results: The patients with TGA were significantly impaired in their performance on the 20-minute delayed recall of the HVLT. They also exhibited significantly decreased rCBF on their SPECT scans in the inferior and middle frontal gyrus bilaterally, with more prominent left-sided reductions in the superior temporal, precentral, and postcentral gyri, as well as increased rCBF primarily in the right hemisphere within the middle temporal, superior temporal, and inferior frontal gyri, cerebellum, and thalamus, compared with the normal control group. Conclusion: These findings suggest that lateralized abnormalities in brain functioning are an important component of the pathophysiology of TGA. Lateralized abnormalities may disrupt functions that are relatively specific to the left hemisphere, including receptive language, symbolic representation, and the processing of local features in the environment, while preserving anterograde memory processes. Increased flow to the right hemisphere centered on regions that subserve the functions of expressive language and visuospatial processing, and may represent processes that compensate for flow reductions to the left hemisphere. [Copyright &y& Elsevier]

Objectives: This study aimed to evaluate the clinical characteristics and clinical course of Asian elderly-onset Crohn’s disease (EOCD) patients in a large well-defined cohort of South Korean IBD patients. Materials and methods: From the Asan inflammatory bowel disease registry, we identified 29 EOCD patients (diagnosed with CD in age of 60 years or over) out of 2989 CD patients (1.0%). After excluding two patients with unclear data, 27 EOCD were matched with 108 young-onset CD (YOCD) and 108 middle age-onset CD (MOCD) for the interval from symptom onset to diagnosis (±3 years) and follow-up duration (±3 years). Results: Females were predominant in the EOCD group (59.3%) compared to MOCD (31.5%) and YOCD (29.6%) groups (p = .012). In EOCD group, terminal ileal location was the most common (63.0%) at diagnosis, whereas ileocolonic location in other groups (57.4% in MOCD and 78.7% in YOCD, respectively) (p < .001). Patients with perianal fistula at CD diagnosis were less common (14.8% in EOCD vs. 28.7% in MOCD vs. 49.1% in YOCD, p < .001). During follow-up, thiopurines were used less frequently in the EOCD group (48.1% in EOCD vs. 87.0% in MOCD vs. 89.8% in YOCD, p < .001), but the risk for intestinal resection was comparable among three groups (p = .583). Conclusions: EOCD may have a better clinical course than MOCD and YOCD, as demonstrated by the similar risk for intestinal resection despite the less frequent use of thiopurines. [ABSTRACT FROM AUTHOR]

Background: Incidence of and risk factors for intestinal free perforation (FP) in patients with Crohn's disease (CD) are not established.Aim: To establish rate of and risk factors for FP in a large cohort of CD patients.Methods: Medical records of CD patients who visited Asan Medical Center from June 1989 to December 2012 were reviewed. After matching the FP patients to controls (1:4) by gender, year, and age at CD diagnosis, and disease location, their clinical characteristics were compared using conditional logistic regression analysis.Results: Among 2043 patients who were included in our study cohort, 44 patients (2.15%) developed FP over a median follow-up period of 79.8 months (interquartile range 37.3-124.6), with an incidence of 3.18 per 1000 person-years [95% confidence interval (CI) 2.37-4.28]. All 44 patients underwent emergency surgery, and eight patients underwent reoperation within 12 months (8/44, 18.2%). Multivariable-adjusted analysis revealed that anti-TNF therapy [odds ratio (OR), 3.73; 95% CI 1.19-11.69; p = 0.024] was associated with an increased risk of FP.Conclusions: The incidence of FP in a large cohort of Korean CD patients was 2.15%, which was similar to that in Western reports. Anti-TNF therapy could be risk factors for FP. [ABSTRACT FROM AUTHOR]

Background and Aim Limited data are available regarding mortality from inflammatory bowel disease in non-Caucasian populations. Herein, we evaluated overall and cause-specific mortality in a hospital-based cohort of Korean inflammatory bowel disease patients. Methods We determined mortality in 2414 Crohn's disease patients and 2798 ulcerative colitis patients diagnosed between 1977 and 2013. Standardized mortality ratios were calculated in several demographic and phenotypic subgroups. Results During the mean 9-year follow up, 114 patients died: 35 with Crohn's disease and 79 with ulcerative colitis. The overall standardized mortality ratios were 1.40 (95% confidence interval: 0.97-1.94) in Crohn's disease and 0.73 (0.58-0.91) in ulcerative colitis. In Crohn's disease, female sex, age < 30 years at diagnosis, disease duration > 10 years, ileocolonic disease at diagnosis, perianal fistula, intestinal resection, and ever-use of corticosteroids were associated with higher mortality. In ulcerative colitis, male sex, age ≥ 30 years at diagnosis, disease duration ≤ 5 years, proctitis at diagnosis, and no history of colectomy were associated with lower mortality, while primary sclerosing cholangitis was associated with higher mortality. In both Crohn's disease and ulcerative colitis, high mortality rates due to nonmalignant gastrointestinal causes (standardized mortality ratios: 4.59 and 2.32, respectively) and gastrointestinal malignancies (standardized mortality ratios: 16.59 and 3.45, respectively) were observed. Cardiovascular mortality was lower in ulcerative colitis (standardized mortality ratio: 0.47). Conclusions The overall mortality tended to be higher in Crohn's disease patients than in the general population; it was slightly lower in ulcerative colitis patients than in the general population. [ABSTRACT FROM AUTHOR]

Hyponatremia in the early phase of acute myocardial infarction (AMI) is a well-known predictor of poor prognosis. However, little is known about the clinical implication of sodium levels at discharge in hospital survivors after AMI. The study included 1290 consecutive patients (64 ± 12 years; 877 men) who survived the index hospitalization after AMI. We determined the 12-month mortality rates of these patients. Patients who died during the 12-month follow-up had lower sodium levels at discharge than those who had survived (137 ± 6 vs. 139 ± 4 mmol/L; P < 0.014). Hyponatremia at discharge, defined as a serum sodium level ≤135 mmol/L, was present in 210 patients (16.3 %). In the Cox-proportional hazard model, hyponatremia at discharge (hazard ratio, 2.264; 95 % confidence interval, 1.119-4.579; P = 0.023) was an independent predictor of 12-month mortality. Moreover, hyponatremia at discharge had an incremental prognostic value over conventional risk factors ( χ = 7, P = 0.007), and conventional risk factors and log N-terminal Pro-B-type natriuretic peptide combined ( χ = 5, P = 0.021). In the subgroup analysis, the 12-month mortality of patients with hyponatremia at discharge was significantly higher than in those without, irrespective of age, Killip class, left ventricular ejection fraction, percutaneous coronary intervention at index hospitalization, and prescription of diuretics at discharge. Hyponatremia at discharge is an independent predictor of 12-month mortality in hospital survivors after AMI. [ABSTRACT FROM AUTHOR]

BackgroundThe impact of genetic variation in thethiopurine S-methyltransferase (TPMT)gene on thiopurine-induced leukopenia has been well demonstrated. Although xanthine dehydrogenase (XDH)is the second major contributor to azathioprine breakdown, polymorphisms inXDHhave rarely been studied in IBD patients. We aim to access association betweenXDHvariants and thiopurine-induced leukopenia by gene–gene interaction in a Crohn’s disease (CD) population.StudyA total of 964 CD patients treated with thiopurines were recruited from a tertiary referral center. The association between fourXDHvariants (p.Gly172Arg, p.Asn1109Thr, p.Arg149Cys, and p.Thr910Lys) and thiopurine-induced leukopenia was analyzed in cases with early leukopenia (n = 66), late leukopenia (n = 264), and in controls without leukopenia (n = 632). Three non-synonymous SNPs, which we previously reported association with thiopurine-induced leukopenia,NUDT15(p.Arg139Cys),SUCLA2(p.Ser199Thr), andTPMT *3Cwere selected for epistasis analysis with theXDHvariants.ResultsThere was no significant association for two variants ofXDHand thiopurine-induced leukopenia. In the epistasis analysis, onlyXDH(p.Asn1109Thr) *SUCLA2(p.Ser199Thr) showed a statistically significant association with early leukopenia [odds ratio (OR) = 0.16;p = 0.03]. After genotype stratification, a positive association on the background ofSUCLA2wild-type (199Ser) between theXDH(p.Asn1109Thr) and early leukopenia (OR = 4.39;p = 0.01) was detected.ConclusionGenes associated with thiopurine-induced leukopenia can act in a complex interactive manner. Further studies are warranted to explore the mechanisms underlying the effects of the combination ofXDH(p.Asn1109Thr) andSUCLA2(199Ser) on thiopurine-induced leukopenia. [ABSTRACT FROM PUBLISHER]

Polycystic ovary syndrome (PCOS), characterized with menstrual irregularities, hyperandrogenism and ovulatory abnormalities, is usually companied with insulin resistance (IR) and accounts for one of the most prevalent reproductive dysfunction of premenopausal women. Despite accumulating investigations, diagnostic standards of this pathological condition remain obscure. The aim of present study is to characterize the plasma metabolic characteristics of PCOS patients with and without IR, and subsequently identify the potential biomarkers for the diagnosis of PCOS and its IR complication. A total of 59 plasma samples from eligible healthy controls (CON, n = 19), PCOS patients without IR (non-IR PCOS, n = 19) and PCOS patients with IR (IR PCOS, n = 21) were profiled by an ultra high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOFMS) followed by multivariate statistical analysis. Compared to the healthy controls, significant decrease in the levels of phosphocholines (PCs) and lyso PC (18:2), and increase in trilauric glyceride level were observed in the plasma of IR PCOS. Meanwhile, the significant increase in the levels of saturated fatty acids (palmitic acid and stearic acid) and decanoylcarnitine, and decrease in PC (36:2) and PS (36:0) were found in non-IR PCOS patients. Trilauric glyceride and decanoylcarnitine were identified as the potential biomarkers with the highest sensitivity and specificity for the diagnosis of PCOS patients with and without IR, respectively. Furthermore, based on these alterations of metabolites, MetPA network pathway analysis suggested a profound involvement of the abnormalities of glycerophospholipid, glycerolipid and fatty acid metabolisms in the pathogenesis of PCOS and IR complications. Collectively, LC–MS-based metabolomics provides a promising strategy for complementary diagnosis of PCOS and its IR complication and offers a new insight to understand their pathogenesis mechanisms. [ABSTRACT FROM AUTHOR]

Impaired renal function is regarded as a risk factor for vascular disease, and is associated with an increasing pulse wave velocity. Both renal dysfunction and arterial stiffness are associated with cognitive impairment and dementia. However, there have been few studies that have evaluated the relationship between albuminuria and arterial stiffness and Alzheimer's disease (AD). We investigated renal dysfunction and arterial stiffness in AD, as compared to normal controls, patients with subjective memory impairment (SMI), and patients with mild cognitive impairment (MCI). Case-control comparisons were made between 29 patients with AD, 27 with MCI, 14 with SMI, and 25 healthy controls. All patients underwent clinical and neuropsychological assessments. The urine albumin/creatinine ratio and estimated glomerular filtration rate (eGFR) were determined. Pulse wave velocity and the ankle-brachial index were used to evaluate arterial stiffness. The urine albumin/creatinine ratio and eGFR were significantly different in patients with AD, compared with the results from cognitive normal controls. The pulse wave velocity was increased and the ankle-brachial index was decreased in AD. The eGFR was well correlated with other indices and decreasing eGFR was independently associated with cognitive decline. In conclusion, albuminuria, a decreased glomerular filtration rate, an increased pulse wave velocity, and a decreased ankle-brachial index were associated with AD. These finding suggests that impaired renal functions and arterial stiffness are related to AD, in which a vascular mechanism plays a prominent role in the cognitive dysfunction associated with the disease. [ABSTRACT FROM AUTHOR]

Background Although adoption of new clinical criteria for dementia with Lewy bodies (DLB) leads to an increase in the proportion of patients diagnosed with probable DLB, the sensitivity of clinical diagnostic criteria of DLB is low, and there are no generally accepted clinical or imaging biomarkers to distinguish DLB from other types of dementia. In this study, we investigated whether neurocirculatory abnormalities and cardiac sympathetic denervation differed in controls and patients with subjective memory impairment (SMI), mild cognitive impairment (MCI), Alzheimer's disease (AD), and DLB. We also assessed whether spontaneous features of Parkinsonism might be related to the neurocirculatory abnormalities and cardiac sympathetic denervation found in DLB. Methods Twenty-two consecutive patients with probable DLB were enrolled in this study; 25 age-matched controls, 14 SMI, 24 MCI, and 37 AD patients were also evaluated. Metaiodobenzylguanidine (MIBG) uptake was assessed using the ratio of the heart to the upper mediastinum (H/M ratio), and orthostatic vital signs and ambulatory 24-hour blood pressure monitoring values were recorded. Results The mean H/M ratio was significantly lower and the proportion of orthostatic hypotension was higher in patients with DLB than in controls, SMI, MCI and AD patients. In patients with DLB, spontaneous Parkinsonism was not related to the degree of cardiac sympathetic denervation nor did it influence neurocirculatory abnormalities. Conclusion Our results suggest that MIBG scintigraphy and autonomic function tests may be useful for distinguishing between DLB and AD in clinical practice. Myocardial postganglionic sympathetic denervation and autonomic dysfunctions are present in patients with DLB regardless of spontaneous Parkinsonism. [ABSTRACT FROM AUTHOR]

An imbalance between T helper 1 (Th1) and T helper 2 (Th2) cells has been reported to increase plaque instability in patients with unstable angina (UA). MicroRNAs play a vital role in the differentiation of CD4+ T cells. However, the role of microRNAs in regulation of Th1/Th2 balance in UA remains unclear. In this study, we aimed to elucidate microRNA expression profiles of circulating CD4+ T cells in UA and to explore the function of microRNAs in the Th1/Th2 balance. A total of 53 patients with UA and 31 control subjects without coronary artery disease were enrolled. Microarray analysis of the microRNA expression profiles of CD4+ T cells revealed that miR-155 was the most significantly upregulated microRNA of the 451 differentially expressed microRNAs. The upregulation of miR-155 expression was positively correlated with the percentage of Th1 cells and interferon-gamma (IFN-γ) levels in patients with UA. In addition, overexpression of miR-155 in human circulating CD4+ T cells promoted Th1 differentiation. Further studies identified IFN-γ receptor alpha chain ( IFN-γ Rα) mRNA as a direct and functional target of miR-155. A luciferase reporter assay verified that miR-155 directly targeted IFN-γ Rα mRNA. Small-interfering RNA-mediated knockdown of IFN-γ Rα mRNA showed effects similar to those of ectopic miR-155 expression. Thus, our study indicated that upregulation of miR-155 in circulating CD4+ T cells in patients with UA promoted a shift in the Th1/Th2 balance toward Th1 dominance by repressing IFN-γ Rα, which may subsequently enhance plaque instability. J. Cell. Physiol. 230: 2498-2509, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background and purpose White matter hyperintensities (WMHs) in the cholinergic pathways are associated with cognitive performance in Alzheimer's disease (AD) and Parkinson disease dementia (PDD). This study aimed to evaluate the relationship between loss of white matter cholinergic pathways and cognitive function in patients with AD, diffuse Lewy body disease (DLB), and PDD. Methods The subjects included 20 patients with AD, 17 with DLB, 21 with PDD, and 20 healthy controls. The extent of WMHs within cholinergic pathways was assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS) and was compared among the different diseases. Results The mean CHIPS scores were similar among the three dementia groups (AD vs. DLB vs. PDD = 34.6 ± 17.9 vs. 32.4 ± 14.1 vs. 31.8 ± 14.5, p = 0.781 by ANCOVA) and higher than those of controls (11.5 ± 7.6, p = 0.001 by ANCOVA). Conclusions Losses of cholinergic pathways were similar among AD, DLB, and PDD groups, and more severe cognitive dysfunction was associated with elevated WMHs. These findings suggest that interruption of acetylcholine pathways may be related to cognitive dysfunction in these three diseases, even though they have different pathological mechanisms. [ABSTRACT FROM AUTHOR]

Highlights: [•] Plasma phospholipid fatty acid profile for PCOS patients with and without IR has been characterized. [•] An GC–MS followed by multivariate statistical analysis was employed. [•] C24:1 n-9 and C20:3 n-6 were identified as the potential FA biomarkers of PCOS and its IR, respectively. [•] GC–MS-based FA profile might provide a complementary approach for diagnosis of PCOS and its IR. [ABSTRACT FROM AUTHOR]

Objectives: Some patients with suspected ST-segment elevation (STE) myocardial infarction (STEMI) show STE that does not fulfill the current criteria for STEMI. The purpose of this study was to investigate the characteristics and prognoses of patients with minimal STEMI. Methods: Between November 2007 and December 2011, 546 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI were enrolled. Results: The minimal STE group had a higher proportion of women (30.2 vs. 21.0%, p = 0.031), better pre-PCI antegrade flow (Thrombolysis in Myocardial Infarction flow 2-3, 30.2 vs. 18.8%, p = 0.006) and better collateralization (Rentrop score 2-3, 27.4 vs. 18.1%, p = 0.024) compared to the definite STE group. Multivariate analysis showed that each of them were independent predictors for minimal STE. However, 1-year mortality of the minimal STE group did not differ from that of the definite STE group (7.1 vs. 9.3%, log-rank p = 0.315). Conclusions: Female gender, good collateral flow and good pre-PCI antegrade flow were independent predictors for minimal STE in patients with STEMI. However, minimal STE was not related to a good prognosis in patients with STEMI. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background & Aims: The natural course of chronic hepatitis B virus (HBV) infection is characterized by different immune responses, ranging from immune tolerant (IT) to immune activated (IA) stages. In our study, we investigated the natural killer (NK) cells activity in patients at different immunological stages of chronic HBV infection. Methods: Blood samples obtained from 57 HBeAg positive patients with chronic hepatitis B (CHB), including 15 patients in the immune tolerant (IT) stage, 42 patients in the immune activated (IA) stage, and 18 healthy individuals (HI). The analyses included flow cytometry to detect NK cells, the determination of cytokine levels as well as of surface receptor expression and cytotoxicity. Results: NK cells in peripheral blood were significantly lower in patients in the IA stage of CHB compared to HI (p<0.05). Patients in the IA stage of CHB had lower levels of NK cells activating receptor NKp30 and NKG2D expression, cytokine interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, as compared to patients in the IT stage and HI, respectively (p<0.05). Cytotoxicity of NK cells was lower in patients in the IA stage of CHB compared to patients in the IT stage and HI, respectively (p<0.05). The level of IFN-γ but not level of TNF-α and cytotoxicity of NK cells was inversely correlated with serum HBV load in patients with CHB. Peripheral NK cells activity did not correlate with ALT level. Conclusion: NK cells activity was lower in CHB patients, especially in those in the IA stage. [ABSTRACT FROM AUTHOR]

Objective. The long-term efficacy of azathioprine (AZA) in steroid-dependent ulcerative colitis (UC) is still unclear. We aimed to evaluate the efficacy of AZA in patients with steroid-dependent UC. Material and methods. We retrospectively reviewed die medical records of 106 patients with steroid-dependent UC who were administered AZA. Three-year outcomes of AZA therapy were evaluated. The outcome of the treatment was defined as (1) success, indicating induction and maintenance of remission throughout the study period (complete success) or remission followed by infrequent and short relapses (partial success); or (2) failure, indicating the absence of remission, frequent or prolonged relapses, infliximab administration, or colectomy. Results. Of the 106 patients, 73 (68.9%) continued on AZA for >6 months (AZA therapy group) and 33 (31.1%) discontinued AZA within 6 months due to intolerance (AZA intolerance group, n = 20), colectomy (n = 6), or follow-up loss (n = 7). Three-year outcomes for 106 patients were success in 54.7% (complete success, 35.8%; partial success, 18.9%), failure in 32.1% (frequent or prolonged relapses, 12.3%; infliximab administration, 5.6%; colectomy, 14.2%), and follow-up loss or death in 13.2%. The success rate increased to 71.2% (complete success, 46.6%; partial success, 24.7%) when the analysis was confined to the 73 patients who continued AZA for > 6 months. The 3-year success rate was higher in the AZA therapy group (71.2%) than the AZA intolerance group (25.0%) (p < 0.001). Conclusions. AZA is an effective treatment for steroid-dependent UC. The efficacy of AZA is well sustained over 3 years. [ABSTRACT FROM AUTHOR]

Background and Aim Chronic constipation is frequently seen in women who have undergone hysterectomy or delivery. However, reports regarding anorectal physiologic features in those patients are rare. Patients with constipation associated with either radical hysterectomy or vaginal delivery were analyzed in order to clarify the anorectal physiologic features and the effectiveness of biofeedback therapy. Methods Of the constipated patients, a hysterectomy group ( n = 40), delivery group ( n = 41), and a control group ( n = 89), who had no history of either surgery or delivery before developing functional constipation were included. Their anorectal physiological tests and the effectiveness of biofeedback therapy were investigated. Results The volume of desire to defecate was greater in the hysterectomy group than in the control group (86.5 ± 55.0 mL vs 62.9 ± 33.7 mL; P = 0.03), and more than 240 mL of maximal volume of toleration was more frequently noted in the hysterectomy group (32.5%) than in the delivery group (14.6%) and control group (13.5%) ( P = 0.02).The failure of balloon expulsion was more frequently noted in the delivery group (44.0%) than in the hysterectomy group (15.0%) and control group (25.0%) ( P = 0.01). The defecation satisfaction score was significantly increased after biofeedback therapy in the hysterectomy group (2.0 ± 2.7 vs 7.8 ± 1.5, P < 0.001), the delivery group (1.6 ± 2.1 vs 6.7 ± 2.0, P < 0.001), and the control group (2.5 ± 2.7 vs 6.9 ± 2.1, P < 0.001). Conclusions Rectal hyposensitivity could have been the characteristic mechanism in the hysterectomy group, whereas dyssynergic defecation could have been the cause in the delivery group. Biofeedback therapy was effective for both groups. [ABSTRACT FROM AUTHOR]

Abstract: Background: It is still controversial whether carotid plaque is associated with cardiovascular events in patients with coronary artery disease (CAD). The aim of the present study is to evaluate the impact of carotid plaque on long term clinical outcomes especially in patients with CAD. Methods: The study population consisted of 1390 consecutive patients with angiographically proven CAD. All subjects underwent carotid scanning 1day before or after coronary angiogram and were followed up for major adverse cardiovascular events (MACE; death, myocardial infarction, stroke, revascularization, restenosis and hospitalization for heart failure) during a mean of 54.2±23.9months. Results: Patients with carotid plaque (n=433) were older, had higher prevalence of cardiovascular risk factors and acute coronary syndrome (34.2% vs. 24.6%, p<0.001) than those without carotid plaque (n=957). On univariate analysis, the presence of carotid plaque was a predictor of cardiac death, hard MACE (death, myocardial infarction and stroke) and total MACE, whereas carotid intima-media thickness (CIMT) was a predictor of total MACE. Multivariate analysis revealed that carotid plaque was associated with cardiac death (HR 6.99, 95% CI 1.88–25.95, p=0.004), hard MACE (HR 1.89, 95% CI 1.18–3.04, p=0.008) and total MACE (HR 1.47, 95% CI 1.13–1.90, p=0.004), whereas CIMT was associated only with total MACE (HR 1.39, 95% CI 1.06–1.81, p=0.017). Conclusions: Carotid plaque is a strong predictor of future cardiac death and MACE in patients with CAD. This study suggests that carotid plaque has additional value for secondary prevention and more important prognostic factor than CIMT in patients with CAD. [Copyright &y& Elsevier]

Background/Aims: The role of vitamin D in the process of vascular calcification is unclear in patients with chronic kidney disease. We investigated whether serum 25-hydroxyvitamin D [25(OH)D] is associated with vascular calcification in predialysis and dialysis patients. Methods: We included 86 predialysis and 139 dialysis patients. The simple vascular calcification score (SVCS) was evaluated by examining plain X-rays of the pelvis and hands as described previously. The carotid-to-femoral pulse wave velocity (CF-PWV) was assessed with a commercially available device. Results: We found a high prevalence of vitamin D deficiency in our population (78.2%). Vascular calcification was present in 46.2% of all patients. Higher calcification (SVCS >3) was significantly associated with lower 25(OH)D levels in predialysis and dialysis patients. Multiple logistic regression analysis for SVCS >3 showed that 25(OH)D levels were negative independent predictors in predialysis (OR: 0.781; 95% CI: 0.623-0.908, p = 0.019) and dialysis patients (OR: 0.805; 95% CI: 0.749-0.853, p = 0.009). Lower 25(OH)D levels were associated with higher CF-PWV in predialysis patients, but this inverse relationship was no longer present in multivariate analysis. Conclusion: We showed an independent relationship between low serum 25(OH)D levels and vascular calcification in both predialysis and dialysis patients. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

There have been no studies that have assessed the possible correlation between conduction abnormality (CA) and systemic embolism, or the long-term outcomes of patients with infective endocarditis (IE). In this study, 82 consecutive patients with IE and interpretable electrocardiography (ECG) were admitted to Kyungpook National University Hospital from July 2002 to June 2008. ECGs obtained at the time of admission or during hospitalization were analyzed. Patients with CA, which was defined as atrioventricular or intraventricular block, of 'new' or 'of unknown duration' were considered as those with CA. Composite events were defined as the composite of death and embolic events. Twenty-three (28%) patients had CA classified as new ( n = 11) or of unknown duration ( n = 12). No significant differences were found between patients with and without CA in terms of age and gender. Mean follow-up duration was 21 ± 23 months. Patients with CA had more frequent embolic events ( p = 0.001) and composite events ( p = 0.002) during hospitalization, and had more frequent composite events ( p < 0.001) during follow-up than those without CA. Kaplan-Meier survival curves showed that patients with CA had a higher composite event rate during follow-up ( p = 0.003). However, there was no significant difference between the two groups regarding mortality rates during hospitalization and follow-up. In multivariate analysis, CA was an independent predictor of embolic event rates during hospitalization [odds ratio (OR) 5.198, 95% confidence interval (CI) 1.086-24.867, p = 0.039] and of composite event rates during follow-up (OR 27.168, 95% CI 4.590-160.802, p < 0.001). CA is associated with increased frequency of embolic events during hospitalization and follow-up. Moreover, CA might be a useful predictor of embolic event occurrences during both hospitalization and follow-up. [ABSTRACT FROM AUTHOR]

Little is known about risk factors for 6-month major adverse cardiac events (MACEs) in 30-day survivors after acute myocardial infarction (AMI). We investigated predictors of 6-month MACE in 30-day survivors after MI from the Korea Acute Myocardial Infarction Registry (KAMIR). From November 2005 to January 2008, 9,706 patients (6,983 men, mean age 64.0 ± 12.4 years) who survived >30 days after AMI were analyzed. The primary end point was 6-month MACEs including death, MI, and revascularization. During 6-month follow-up, 317 patients (3.2%) had MACEs including 66 (0.6%) deaths, 23 (0.2%) recurrent MIs, and 218 (2.2%) revascularizations. In multivariate logistic regression analysis, factors reflecting demographics (body mass index), severity of left ventricular systolic dysfunction (Killip class >I, in-hospital cardiogenic shock, use of intra-aortic balloon pump), residual myocardial ischemia (previous coronary heart disease, multivessel disease), and electrical instability (ventricular tachycardia/ventricular fibrillation on admission) were independent predictors of 6-month MACEs after adjustment for clinical, angiographic, and procedural data. Plasma level of N-terminal pro–B-type natriuretic peptide provided an additional prognostic value predicting 6-month MACEs. In conclusion, this study provides useful prognostic information for clinicians to advise patients who have survived the acute phase of MI. More intensive management is needed in survivors after MI with these high-risk features. [Copyright &y& Elsevier]

BACKGROUND In addition to dermatologists and plastic surgeons, physicians of other medical specialties also provide cosmetic laser and light treatment. OBJECTIVE This study aimed to determine the major decision factors in patients who received cosmetic laser or intense pulsed light treatment and how they perceived different medical specialties in providing such services. METHODS The method of factor analysis was adopted to extract the common characteristics (major decision factors) from a list of 17 items patients would regard as important when they planned to receive laser and intense pulsed light treatment. In addition, the level of recognition of different medical specialties in cosmetic patients was indirectly forecast using an analytic hierarchy process. RESULTS Medical competence (0.3296) was the most important decision factor, followed by recommendation (0.2198), friendliness (0.1350), cost (0.1307), complete service (0.0984), and the physical attributes of the physician (0.0865). Dermatologists and plastic surgeons outscored cosmetic practitioners in five factors except for cost, in which the plastic surgeons were weakest. CONCLUSION Medical competence and recommendation are the core issues for cosmetic patients. Dermatologists and plastic surgeons gain better overall recognition than physicians of other medical specialties in cosmetic patients. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s00330-020-07552-8 [ABSTRACT FROM AUTHOR]