Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis

AIMS: To assess, in tissue microarray (TMA), the proliferative activity of endometrial carcinoma using one of the minichromosome maintenance (MCM) proteins (MCM7), and to explore its potential value for prognosis. MCM proteins are essential for eukaryotic DNA replication and have recently been used to define the proliferative compartments in human tissues. METHODS AND RESULTS: Immunohistochemistry for MCM7 and Ki67 was performed on TMAs constructed from 212 cases of endometrial carcinoma. MCM7 and Ki67 expression was quantified according to the extent of nuclear staining. An analysis was carried out of the association between MCM7 expression and that of Ki67 and the clinicopathological characteristics of endometrial carcinoma. MCM7 and Ki67 immunoreactivity was clearly evident in the nuclei of tumour cells. MCM7 and Ki67 labelling indices in endometrial carcinomas correlated with each other (P < 0.001). A significant correlation existed between the MCM7 labelling index and histological grade (P = 0.008) and patients' age at diagnosis (P < 0.001). Well-differentiated carcinomas and younger patients had a lower MCM7 index. Poor survival was observed in patients with endometrial carcinoma with a high MCM7 index (P = 0.03) and MCM7 was found to be an independent prognostic factor by multivariate analysis (P = 0.04). The Ki67 labelling index correlated with histological grade (P = 0.01) but had no significant prognostic impact (P = 0.50). CONCLUSIONS: In this TMA study on endometrial carcinoma, MCM7 was found to be a more reliable and useful marker than Ki67 in assessing tumour proliferation and in the prognosis of patients.     

The Kinmen women-health investigation (KIWI): a menopausal study of a population aged 40-54

OBJECTIVES: This paper aims to report the methodology of a study of a cohort of middle-aged women in Taiwan, their age at menopause, and related factors and prevalence of menopausal symptoms, and to examine the relationships between symptoms and sociodemographic variables. METHODS: An epidemiological study of neuropsychological change during the menopausal transition among Chinese women aged 40-54 years old on the islet of Kinmen. RESULTS: Of a targeted population of 2256 individuals, 1497 (66%) participated in the study. The mean age at menarche was 15.6 years and that at menopause was 48 years. The hormone use rate at the time of study was 23% in surgical menopausal women, and 9% were past users. After excluding surgical menopausal and premenopausal women, 6% reported a current use of estrogen replacement therapy and 6% were past users. The most frequently reported discomforts for those women aged >45 were troubled sleep, backaches, and joint pain. Four symptom clusters: musculoskeletal, non-specific somatic complaints, urogenital, and vasomotor, were identified. After adjustment for age, the urogenital and vasomotor symptoms were significantly associated with menopausal status. CONCLUSIONS: The age at menopause did not differ much from Western studies, but the menopausal symptoms, especially the vasomotor symptoms, were much lower in our study population. Nevertheless, vasomotor symptoms were still significantly associated with menopausal status.     

Molecular cloning and physical characterization of integrated equine infectious anemia virus: molecular and immunologic evidence of its close relationship to ovine and caprine lentiviruses

Molecular clones of the integrated form of the genome of equine infectious anemia virus (EIAV), the etiologic agent of a naturally occurring, worldwide disease of horses, were obtained. The restriction map of a full-length genome was determined. Additional evidence for the close evolutionary relationship between EIAV and a prototype lentivirus (caprine arthritis encephalitis virus) was acquired by Southern blotting and immunological analyses. An interspecies radioimmunoassay was developed in which EIAV and ovine and caprine lentiviruses could be detected equally well. These studies make available precisely defined reagents to pursue the study of the mechanisms of pathogenesis of lentiviral induced diseases.     

Epidemiologic relationship between fluoroquinolone-resistant Salmonella enterica Serovar Choleraesuis strains isolated from humans and pigs in Taiwan (1997 to 2002)

The emergence of ciprofloxacin-resistant Salmonella enterica serovar Choleraesuis in recent years has become an important public health issue in Taiwan. The resistant strains that cause human infections are considered to be from pigs. In this study, we characterized 157 swine and 42 human Salmonella serovar Choleraesuis isolates by pulsed-field gel electrophoresis (PFGE) and drug susceptibility testing to investigate the epidemiologic relationship among the isolates. By PFGE analyses, two major clusters (clusters GA and GB) were identified. Isolates in cluster GA were of both human and swine origins, while those in cluster GB were from pigs only. Among the various genotypes identified, genotype gt-1a was the most prevalent, which was found in 71% (30 of 42) and 48% (76 of 157) of human and swine isolates, respectively. The susceptibility tests for the 106 gt-1a isolates identified 44 susceptibility profiles and showed that 73% of human isolates and 34% of swine isolates were resistant to three fluoroquinolones (ciprofloxacin, enrofloxacin, and norfloxacin). Our findings indicate that a clonal group of Salmonella serovar Choleraesuis may have been circulating in human and swine populations in Taiwan for years and that the fluoroquinolone-resistant Salmonella serovar Choleraesuis strains most likely evolved from a gt-1a clone that emerged in 2000 and that then caused widespread infections in humans and pigs. Nevertheless, it is still debatable whether those Salmonella infections in humans are caused by isolates derived from pigs, on the basis of the higher fluoroquinolone and other antimicrobial resistance percentages in human isolates than in pig isolates.     

Associations between Circulating Markers of Cholesterol Homeostasis and Macrovascular Events among Patients Undergoing Hemodialysis

Current strategies targeting serum cholesterol bring limited benefits to mortality and macrovascular events prevention among hemodialysis patients. Direct measurements and analysis on circulating markers of cholesterol homeostasis could be promising solutions to this bottleneck. We prospectively enrolled 90 maintenance hemodialysis patients and 9 healthy controls in 2019 for 1 year. We measured circulating desmosterol and lathosterol as markers for cholesterol synthesis and campesterol and sitosterol for cholesterol absorption. At baseline, hemodialysis patients showed higher levels of campesterol (p = 0.023) compared to healthy controls. During follow-up, we identified 14 (15.4%) patients who experienced macrovascular events. Comparisons of cholesterol homeostasis markers between cohorts with and without macrovascular events showed no significant differences in markers of cholesterol synthesis or absorption. Using logistic regression analysis, the odds ratio was not statistically significant for the prediction of macrovascular events after full-adjusting for age, sex, diabetes, serum albumin, cholesterol, and triglyceride. We concluded that hemodialysis patients demonstrated higher level of cholesterols absorption, indicated by circulating campesterol compared to healthy subjects. Markers for cholesterol homeostasis were not significantly associated with macrovascular events during a 1-year follow-up. Our results shed light on the novel therapeutic target of modulating cholesterol absorption in HD patients.     

Association between Reduced Serum Zinc and Diastolic Dysfunction in Maintenance Hemodialysis Patients

Diastolic dysfunction is an emerging challenge among hemodialysis (HD) patients, and the associations between serum zinc with echocardiographic parameters and diastolic function remain uncertain. A total of 185 maintenance HD patients were stratified by the tertiles of serum zinc level to compare their clinical characteristics and echocardiography. Correlations of serum zinc levels with echocardiographic parameters were examined using Pearson’s analysis. Univariate and multivariate logistic regression analyses were performed to investigate the determinants of E/e’ ratio >15 and left atrial volume index (LAVI) > 34 mL/m², both indicators of diastolic dysfunction. Patients belonging to the first tertile of serum zinc level had a significantly higher E/e’ ratio and LAVI. Serum zinc levels were negatively correlated with E (r = −0.204, p = 0.005), E/e’ ratio (r = −0.217, p = 0.003), and LAVI (r = −0.197, p = 0.007). In a multivariate analysis, older age, diabetes, coronary artery disease, and lower serum zinc levels (OR = 0.974, 95% CI = 0.950–0.999, p = 0.039) were significantly associated with E/e’ ratio >15. Furthermore, diabetes and lower serum zinc levels (OR = 0.978, 95% CI = 0.958–0.999, p = 0.041) were significantly associated with LAVI >34 mL/m². Reduced serum zinc level was significantly associated with diastolic dysfunction among HD patients. Further prospective studies are warranted to investigate whether zinc supplementation can attenuate cardiac dysfunction in maintenance HD patients.     

Risks of AKI and Major Adverse Clinical Outcomes in Patients with Severe Acute Respiratory Syndrome or Coronavirus Disease 2019

BackgroundSevere acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) are closely related. The effect of AKI on the clinical outcomes of these two conditions is unclear.MethodsThis retrospective, territory-wide cohort study used an electronic public healthcare database in Hong Kong to identify patients with SARS or COVID-19 by diagnosis codes, virologic results, or both. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death.ResultsWe identified 1670 patients with SARS and 1040 patients with COVID-19 (median ages, 41 versus 35 years, respectively). Among patients with SARS, 26% met the primary endpoint versus 5.3% of those with COVID-19. Diabetes mellitus, abnormal liver function, and AKI were factors significantly associated with the primary endpoint among patients with either SARS or COVID-19. Among patients with SARS, 7.9%, 2.1%, and 3.7% developed stage 1, stage 2, and stage 3 AKI, respectively; among those with COVID-19, 6.6%, 0.4%, and 1.1% developed stage 1, stage 2, and stage 3 AKI, respectively. In both groups, factors significantly associated with AKI included diabetes mellitus and hypertension. Among patients with AKI, those with COVID-19 had a lower rate of major adverse clinical outcomes versus patients with SARS. Renal function recovery usually occurred within 30 days after an initial AKI event.ConclusionsAKI rates were higher among patients with SARS than those with COVID-19. AKI was associated with major adverse clinical outcomes for both diseases. Patients with diabetes mellitus and abnormal liver function were also at risk of developing severe consequences after SARS and COVID-19 infection.     

Association between lymphovascular invasion and oncological outcome in node-negative upper tract urothelial carcinoma with different stage

ObjectivesTo evaluate the prognostic impact of lymphovascular invasion (LVI) on node-negative upper tract urothelial carcinoma (UTUC) in patients treated with radical nephroureterectomy (RNU).Materials and methodsA retrospective study was performed in single tertiary referral center of middle Taiwan between 2001 and 2015. Seven hundred and twenty-eight patients were diagnosed of UTUC and underwent RNU with ipsilateral bladder cuff excision including 303 and 195 patients with N0 and Nx status respectively. LVI status was assessed as a prognostic factor for cancer-specific (CSS) and overall survival (OS) using univariate and multivariate Cox regression analysis.ResultsLVI was observed in 82 patients (16.5%). LVI presentation associated with smoking status, advanced tumor stage, high tumor grade, positive surgical margin, and consequence lung/liver/bone metastasis. In the multivariate analysis, LVI was failed to predict CSS, OS, and disease-free survival (DFS) (hazard ratio [HR] [95% confidence interval [CI]: 1.07 [0.55–2.09], 1.05 [0.62–1.79], 1.15 [0.69–1.92], in CSS, OS, DFS, respectively). In the subgroup analysis of pT1-2 disease, the CSS, OS, and DFS were associated with LVI status (HR [95% CI]: 2.29 [0.44–11.84], 3.17 [1.16–8.67], 2.66 [1.04–6.79], in CSS, OS, DFS, respectively). In contrast, there was no difference in pT3 disease.ConclusionIn conclusion, LVI status was not associated with survival outcomes of node-negative UTUC in our study. The subgroup analysis showed different prognostic impacts of LVI status in node-negative UTUC with T1-2 and T3 stage. Further evidence to clarify the prognostic effect is needed to make LVI became a practical factor in clinical decision-making.     

Retrospective study of functional outcomes and disability after non-ischaemic vascular causes of spinal cord dysfunction

Objective: Describe demographic characteristics, functional outcomes and disability following rehabilitation for non-ischemic vascular spinal cord dysfunction (SCDys).Design: Retrospective, open cohort, case series.Setting: Tertiary rehabilitation unit, Victoria, Australia.Participants: Patients with non-ischemic vascular SCDys admitted over a 21-year-period (01/01/1995–31/12/2015) were identified using International Classification of Diseases codes.Outcome Measures: Demographic characteristics, etiology, neurologic classification, length of stay (LOS), and complications. On admission and discharge, the following were collected: functional independence measure (FIM) motor subscale, details on bowel, bladder, mobility, living arrangement, and support services.Results: 36 patients (female 58%; mean age 69 ± 16 years) were identified. The main causes of non-ischemic vascular SCDys were epidural hematoma (39%), dural arteriovenous fistula (17%), and arteriovenous malformation (11%). 22 cases (61%) were iatrogenic. Most (86%) had incomplete paraplegia. Urinary tract infection was the most common complication (64%). Median LOS in rehabilitation was 68 days. Significant improvement in FIM motor scores was observed from admission (median 25, interquartile range [IQR] 20–38) to discharge (median 69, IQR 38–77) (P < 0.001). On discharge, 4 patients (11%) walked >100 m unaided, 6 (17%) walked >100 m with assistive device, 10 (28%) walked >10 m with assistive device, 15 (41%) were wheelchair dependent and 1 (3%) patient remained non-mobile. 20 patients (56%) were discharged home, 8 (22%) to nursing home, and 8 (22%) transferred to another hospital.Conclusion: Most patients returned home with significantly improved functional outcomes compared to rehabilitation admission, but with the majority having ongoing major disabilities based on FIM motor scores.