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Endocrine System Diseases - Top 30 Publications

Screening for Diabetic Retinopathy.

Vitamin D status and its association with insulin resistance among type 2 diabetics: A case -control study in Ghana.

Vitamin D plays a major role in physiological processes that modulate mineral metabolism and immune function with probable link to several chronic and infectious conditions. Emerging data suggests a possible influence of vitamin D on glucose homeostasis. This study sought to provide preliminary information on vitamin D status among Ghanaian type 2 diabetics and assessed its association with glucose homeostasis.

Modeling the shape and composition of the human body using dual energy X-ray absorptiometry images.

There is growing evidence that body shape and regional body composition are strong indicators of metabolic health. The purpose of this study was to develop statistical models that accurately describe holistic body shape, thickness, and leanness. We hypothesized that there are unique body shape features that are predictive of mortality beyond standard clinical measures. We developed algorithms to process whole-body dual-energy X-ray absorptiometry (DXA) scans into body thickness and leanness images. We performed statistical appearance modeling (SAM) and principal component analysis (PCA) to efficiently encode the variance of body shape, leanness, and thickness across sample of 400 older Americans from the Health ABC study. The sample included 200 cases and 200 controls based on 6-year mortality status, matched on sex, race and BMI. The final model contained 52 points outlining the torso, upper arms, thighs, and bony landmarks. Correlation analyses were performed on the PCA parameters to identify body shape features that vary across groups and with metabolic risk. Stepwise logistic regression was performed to identify sex and race, and predict mortality risk as a function of body shape parameters. These parameters are novel body composition features that uniquely identify body phenotypes of different groups and predict mortality risk. Three parameters from a SAM of body leanness and thickness accurately identified sex (training AUC = 0.99) and six accurately identified race (training AUC = 0.91) in the sample dataset. Three parameters from a SAM of only body thickness predicted mortality (training AUC = 0.66, validation AUC = 0.62). Further study is warranted to identify specific shape/composition features that predict other health outcomes.

Metabolic syndrome, serum uric acid and renal risk in patients with T2D.

Metabolic Syndrome (Mets) and increased serum uric acid (SUA), are well known renal risk predictors and often coexist in patients with type 2 diabetes (T2D). Whether they independently contribute to the onset of CKD is at present unclear.

Comorbidities of rheumatoid arthritis: Results from the Korean National Health and Nutrition Examination Survey.

This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010-2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17-2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24-3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05-3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05-2.77), depression (OR 2.38, 95% CI 1.47-3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15-4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment.

The relationship between diabetes and colorectal cancer prognosis: A meta-analysis based on the cohort studies.

Though a meta-analysis reported the effect of diabetes on colorectal prognosis in 2013, a series of large-scale long-term cohort studies has comprehensively reported the outcome effect estimates on the relationship between diabetes and colorectal prognosis, and their results were still consistent.

Range of Risk Factor Levels: Control, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes Mellitus.

Individuals with type 1 diabetes mellitus (T1DM) have a high risk of cardiovascular complications, but it is unknown to what extent fulfilling all cardiovascular treatment goals is associated with residual risk of mortality and cardiovascular outcomes in those with T1DM compared with the general population.

Reversion of BRCA1/2 Germline Mutations Detected in Circulating Tumor DNA From Patients With High-Grade Serous Ovarian Cancer.

Purpose Germline BRCA1 or BRCA2 mutations in patients with high-grade serous ovarian cancer (HGSC) are associated with favorable responses to chemotherapy. However, secondary intragenic (reversion) mutations that restore protein function lead to clinically significant rates of acquired resistance. The goal of this study was to determine whether reversion mutations could be found in an unbiased manner in circulating cell-free DNA (cfDNA) to predict treatment response in HGSC. Patients and Methods Plasma and tumor samples were obtained from 30 patients with HGSC with either BRCA1 or BRCA2 germline mutation. Two cohorts were ascertained: patients with a malignancy before undergoing primary HGSC debulking surgery (n = 14) or patients at disease recurrence (n = 16). Paired tumor and plasma samples were available for most patients (24 of 30). Targeted amplicon, next-generation sequencing was performed using primers that flanked germline mutations, whose design did not rely on prior knowledge of reversion sequences. Results Five patients were identified with intragenic mutations predicted to restore BRCA1/2 open reading frames, including two patients with multiple independent reversion alleles. Reversion mutations were only detected in tumor samples from patients with recurrent disease (five of 16) and only in cfDNA from patients with a tumor-detected reversion (three of five). Findings from a rapid autopsy of a patient with multiple independent reversions indicated that reversion-allele frequency in metastatic sites is an important determinant of assay sensitivity. Abundance of tumor-derived DNA in total cell-free DNA, as measured by TP53 mutant allele frequency, also affected assay sensitivity. All patients with reversions detected in tumor-derived DNA were resistant to platin- or poly ADP ribose polymerase inhibitor-based chemotherapy. Conclusion Reversion mutations can be detected in an unbiased analysis of cfDNA, suggesting clinical utility for predicting chemotherapy response in recurrent HGSC.

Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology.

Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ-specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP.

Proteomics in pediatric cystic craniopharyngioma.

Adamantinomatous craniopharyngioma (ACP) is still often burdened by a poor prognosis in children as far as the risk of recurrence and the quality of life are concerned. Therefore, many efforts are now dedicated to investigate the molecular characteristics of this tumor aiming at finding new therapeutic options. ACP is prevalently a cystic lesion so that an increasing number of researches are focused on the analysis of its cystic content. In the present article, the main results of the current proteomic analysis (PA) on the ACP fluid are summarized. Both "bottom-up" and "top-down" approaches have been utilized. In the bottom-up approach, proteins and peptides are enzymatically or chemically digested prior to liquid chromatography and mass spectrometry analyses. The bottom-up approach pointed out several proteins of the inflammation (namely, α2-HS-glycoprotein, α1-antichymotrypsin and apolipoproteins) as possibly involved in the genesis and growth of the cystic component of ACP. The top-down strategy analyzes proteins and peptides in the intact state, making it particularly suitable for the identification of peptides and low molecular weight proteins and for the characterization of their possible isoforms and post-translational modifications. The top-down approach disclosed the presence of the thymosin β family. Thymosin β4, in particular, which is involved in the cytoskeleton organization and migration of several tumors, could play a role in the progression of ACP. Finally, PA was utilized to investigate alterations in cyst fluid character after treatment with interferon-α. The analyzed samples showed a progressive reduction of the levels of α-defensins (proteins involved in the inflammatory-mediated response) after the intracystic injection of interferon-α, thus reinforcing the hypothesis that inflammation contributes to ACP cyst pathogenesis. Additional studies on the solid component of ACP are still necessary to further validate the previous results and to identify possible markers for targeted therapy.

Models of human adamantinomatous craniopharyngioma tissue: Steps toward an effective adjuvant treatment.

Even though ACP is a benign tumor, treatment is challenging because of the tumor's eloquent location. Today, with the exception of surgical intervention and irradiation, further treatment options are limited. However, ongoing molecular research in this field provides insights into the pathways involved in ACP pathogenesis and reveal a plethora of druggable targets. In the next step, appropriate models are essential to identify the most suitable and effective substances for clinical practice. Primary cell cultures in low passages provide a proper and rapid tool for initial drug potency testing. The patient-derived xenograft (PDX) model accommodates ACP complexity in that it shows respect to the preserved architecture and similar histological appearance to human tumors and therefore provides the most appropriate means for analyzing pharmacological efficacy. Nevertheless, further research is needed to understand in more detail the biological background of ACP pathogenesis, which provides the identification of the best targets in the hierarchy of signaling cascades. ACP models are also important for the continuous testing of new targeting drugs, to establish precision medicine.

Validation of full-field optical coherence tomography in distinguishing malignant and benign tissue in resected pancreatic cancer specimens.

Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States. The minority of patients can undergo curative-intended surgical therapy due to progressive disease stage at time of diagnosis. Nonetheless, tumor involvement of surgical margins is seen in up to 70% of resections, being a strong negative prognostic factor. Real-time intraoperative imaging modalities may aid surgeons to obtain tumor-free resection margins. Full-field optical coherence tomography (FF-OCT) is a promising diagnostic tool using high-resolution white-light interference microscopy without tissue processing. Therefore, we composed an atlas of FF-OCT images of malignant and benign pancreatic tissue, and investigated the accuracy with which the pathologists could distinguish these.

Type 2 diabetes, depressive symptoms and trajectories of cognitive decline in a national sample of community-dwellers: A prospective cohort study.

We examined the individual and synergistic effects of type 2 diabetes and elevated depressive symptoms on memory and executive function trajectories over 10 and eight years of follow-up, respectively. Our sample comprised 10,524 community-dwellers aged ≥50 years in 2002-03 from the English Longitudinal Study of Ageing. With respect to memory (word recall), participants with either diabetes or elevated depressive symptoms recalled significantly fewer words compared with those free of these conditions (reference category), but more words compared with those with both conditions. There was a significant acceleration in the rate of memory decline in participants aged 50-64 years with both conditions (-0.27, 95% CI, -0.45 to -0.08, per study wave), which was not observed in those with either condition or aged ≥65 years. With respect to executive function (animal naming), participants aged ≥65 years with diabetes or those with elevated depressive symptoms named significantly fewer animals compared with the reference category, while those with both conditions named fewer animals compared with any other category. The rate of executive function decline was significantly greater in participants with both conditions (-0.54, 95% CI, -0.99 to -0.10; and -0.71, 95% CI, -1.16 to -0.27, per study wave, for those aged 50-64 and ≥65 years, respectively), but not in participants with either condition. Diabetes and elevated depressive symptoms are inversely associated with memory and executive function, but, individually, do not accelerate cognitive decline. The co-occurrence of diabetes and elevated depressive symptoms significantly accelerates cognitive decline over time, especially among those aged 50-64 years.

Long Noncoding RNA MNX1-AS1 Knockdown Inhibits Cell Proliferation and Migration in Ovarian Cancer.

Long noncoding RNAs (lncRNAs) have recently emerged as pivotal regulators that govern fundamental biological processes and disease pathogenesis. LncRNA MNX1-AS1 has been reported to promote cell proliferation and invasion in gallbladder cancer, but its biological role and regulatory mechanism in ovarian cancer are poorly defined. In this study, it was found that higher expression of lncRNA MNX1-AS1 is closely associated with International Federation of Gynecology and Obstetrics stage and lymphatic metastasis in ovarian cancer patients. RNA interference (RNAi) to downregulate the expression of lncRNA MNX1-AS1 was used in the ovarian cancer cell lines, OVCA433 and SKOV-3. CCK-8, EdU staining, and colony formation assays was used to test the viability and proliferation ability of these cells. Wound healing and transwell migration assays were performed to determine the migration ability of the cells. Cell cycle progression and apoptotic assays were carried out using flow cytometry. These in vitro loss-of-function experiments revealed that downregulation of lncRNA MNX1-AS1 suppressed cell proliferation, colony formation, cell migration ability, induced cell cycle arrest at the G0/G1 phase, and promoted apoptosis. Furthermore, MNX1-AS1 knockdown altered the protein expressions of CDK4, cyclin D, Bax, and Bcl-2. These findings demonstrated for the first time that lncRNA MNX1-AS1 functions as an oncogene in ovarian cancer and could be a potential target for this disease.

Favorable Effect on Blood Volume Control in Hemodialysis Patients with Type 2 Diabetes after Switching from Insulin Therapy to Liraglutide, a Human Glucagon-like Peptide-1 Analog--Results from a Pilot Study in Japan-.

Hemodialysis patients are advised to limit the intake of foods in order to control volume status and body weight (BW). We report the clinical course of five Japanese hemodialysis patients with type 2 diabetes mellitus (T2DM) who were switched from insulin to liraglutide, and the efficacy of the treatment, especially in terms of changes in interdialysis weight gain (IDWG).

Differential adipokine DNA methylation and gene expression in subcutaneous adipose tissue from adult offspring of women with diabetes in pregnancy.

Offspring of women with diabetes in pregnancy are at increased risk of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic mechanisms. The adipokines leptin, adiponectin, and resistin (genes: LEP, ADIPOQ, RETN) play key roles in the pathophysiology of T2DM. We hypothesized that offspring exposed to maternal diabetes exhibit alterations in epigenetic regulation of subcutaneous adipose tissue (SAT) adipokine transcription. We studied adipokine plasma levels, SAT gene expression, and DNA methylation of LEP, ADIPOQ, and RETN in adult offspring of women with gestational diabetes (O-GDM, N = 82) or type 1 diabetes (O-T1DM, N = 67) in pregnancy, compared to offspring of women from the background population (O-BP, N = 57).

Appraising the holistic value of Lenvatinib for radio-iodine refractory differentiated thyroid cancer: A multi-country study applying pragmatic MCDA.

The objective of the study was to reveal through pragmatic MCDA (EVIDEM) the contribution of a broad range of criteria to the value of the orphan drug lenvatinib for radioiodine refractory differentiated thyroid cancer (RR-DTC) in country-specific contexts.

Diabetes mellitus in patients with chronic obstructive pulmonary disease-The impact on mortality.

Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There is evidence to support a connection between COPD and diabetes mellitus (DM), another common medical disorder. However, additional research is required to improve our knowledge of these relationships and their possible implications. In this study, we investigated the impact of DM on patient outcomes through the clinical course of COPD.

Inherited variants in genes somatically mutated in thyroid cancer.

Tumour suppressor genes when mutated in the germline cause various cancers, but they can also be somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic well-differentiated thyroid cancer (WDTC).

Altered glucose metabolism and hypoxic response in alloxan-induced diabetic atherosclerosis in rabbits.

Diabetes mellitus accelerates atherosclerosis that causes most cardiovascular events. Several metabolic pathways are considered to contribute to the development of atherosclerosis, but comprehensive metabolic alterations to atherosclerotic arterial cells remain unknown. The present study investigated metabolic changes and their relationship to vascular histopathological changes in the atherosclerotic arteries of rabbits with alloxan-induced diabetes. Diabetic atherosclerosis was induced in rabbit ilio-femoral arteries by injecting alloxan (100 mg/kg), injuring the arteries using a balloon, and feeding with a 0.5% cholesterol diet. We histologically assessed the atherosclerotic lesion development, cellular content, pimonidazole positive-hypoxic area, the nuclear localization of hypoxia-inducible factor-1α, and apoptosis. We evaluated comprehensive arterial metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using 18F-fluorodeoxyglucose and pimonidazole. Plaque burden, macrophage content, and hypoxic areas were more prevalent in arteries with diabetic, than non-diabetic atherosclerosis. Metabolomic analyses highlighted 12 metabolites that were significantly altered between diabetic and non-diabetic atherosclerosis. A half of them were associated with glycolysis metabolites, and their levels were decreased in diabetic atherosclerosis. The uptake of glucose evaluated as 18F-fluorodeoxyglucose in atherosclerotic lesions increased according to increased macrophage content or hypoxic areas in non-diabetic, but not diabetic rabbits. Despite profound hypoxic areas, the nuclear localization of hypoxia-inducible factor-1α decreased and the number of apoptotic cells increased in diabetic atherosclerotic lesions. Altered glycolysis metabolism and an impaired response to hypoxia in atherosclerotic lesions under conditions of insulin-dependent diabetes might be involved in the development of diabetic atherosclerosis.

Interleukin-10 and prostaglandin E2 have complementary but distinct suppressive effects on Toll-like receptor-mediated dendritic cell activation in ovarian carcinoma.

Dendritic cells (DC) have the potential to instigate a tumour-specific immune response, but their ability to prime naïve lymphocytes depends on their activation status. Thus, for tumour immunotherapy to be effective, the provision of appropriate DC activation stimuli such as Toll-like receptor (TLR) agonists is crucial in order to overcome immunosuppression associated with the tumour microenvironment. To address this, we investigated how ovarian carcinoma (OC)-associated ascites impedes activation of DC by TLR agonists. Our results show that ascites reduces the TLR-mediated up-regulation of CD86 and partially inhibits the production of the pro-inflammatory cytokines interleukin 6 (IL-6), IL-12 and tumour necrosis factor α (TNFα) in monocyte-derived DC from healthy controls. We further observe an impaired T cell stimulatory capacity of DC upon activation with TLR agonists in the presence of ascites, indicating that their functionality is affected by the immunosuppressive factors. We identify IL-10 and prostaglandin E2 (PGE2) as the pivotal immunosuppressive components in OC-associated ascites compromising TLR-mediated DC activation. Interestingly, IL-10 is present in both ascites from patients with malignant OC and in peritoneal fluid from patients with benign ovarian conditions and both fluids have similar ability to reduce TLR-mediated DC activation. However, depletion of IL-10 from ascites revealed that the presence of paracrine IL-10 is not crucial for ascites-mediated suppression of DC activation in response to TLR activation. Unlike IL-10, PGE2 is absent from peritoneal fluid of patients with benign conditions and selectively reduces TNFα induction in response to TLR-mediated activation in the presence of OC-associated ascites. Our study highlights PGE2 as an immunosuppressive component of the malignant OC microenvironment rendering PGE2 a potentially important target for immunotherapy in OC.

Primary, secondary and compensated hypogonadism: a novel risk stratification for infertile men.

Recently, the cohort of men from the European Male Ageing Study has been stratified into different categories distinguishing primary, secondary and compensated hypogonadism. A similar classification has not yet been applied to the infertile population. We performed a cross-sectional study enrolling 786 consecutive Caucasian-European infertile men segregated into eugonadal [normal serum total testosterone (≥3.03 ng/mL) and normal luteinizing hormone (≤9.4 mU/mL)], secondary (low total testosterone, low/normal luteinizing hormone), primary (low total testosterone, elevated luteinizing hormone) and compensated hypogonadism (normal total testosterone; elevated luteinizing hormone). In this cross-sectional study, logistic regression models tested the association between semen parameters, clinical characteristics and the defined gonadal status. Eugonadism, secondary, primary and compensated hypogonadism were found in 80, 15, 2, and 3% of men respectively. Secondary hypogonadal men were at highest risk for obesity [OR (95% CI): 3.48 (1.98-6.01)]. Primary hypogonadal men were those at highest risk for azoospermia [24.54 (6.39-161.39)] and testicular volume <15 mL [12.80 (3.40-83.26)]. Compensated had a similar profile to primary hypogonadal men, while their risk of azoospermia [5.31 (2.25-13.10)] and small testicular volume [8.04 (3.17-24.66)] was lower. The risk of small testicular volume [1.52 (1.01-2.33)] and azoospermia [1.76 (1.09-2.82)] was increased, although in a milder fashion, in secondary hypogonadal men as well. Overall, primary and compensated hypogonadism depicted the worst clinical picture in terms of impaired fertility. Although not specifically designed for infertile men, European Male Ageing Study categories might serve as a clinical stratification tool even in this setting.

Testosterone level and endothelial dysfunction in patients with vasculogenic erectile dysfunction.

The association between endothelial dysfunction and late onset hypogonadism (LOH) in patients with vasculogenic erectile dysfunction (ED) is not yet well settled. Our objective was to assess the association between LOH and endothelial dysfunction in patients with vasculogenic ED. Throughout 2014-2015 a total of 90 men were enrolled in this cross-sectional observational study. Of them 60 patients with a clinical diagnosis of ED were further subdivided into two equal groups: patients with vasculogenic ED and LOH (A); patients with vasculogenic ED and euogonadal (B). Thirty age-matched men with no ED or hypogonadism were enrolled as control group (C). All patients were subjected to detailed medical and sexual history, total testosterone (TT), calculated free (FT) and bioavailable testosterone (BT), flow cytometric evaluation for endothelial progenitor cells (EPCs) (CD45negative/CD34positive/CD144positive) and endothelial microparticles (EMPs) (CD45negative/CD144positive/annexin V positive). The mean age ± SD of the three groups A, B and C were 51.3 ± 11.1, 53.6 ± 10.6 and 48.3 ± 5 years, respectively, with insignificant age differences (p = 0.089). The diagnostic criteria of LOH were adapted according to European male aging study, 2010. The means of TT(ng/mL) were 2.32 ± 0.21, 6.43 ± 0.36 and 5.37 ± 0.30 in groups A, B and C, respectively. There were highly significant differences between group A and groups B and C (p < 0.001 for each). The means of EPCs were 0.43 ± 0.070, 0.22 ± 0.05 and 0.032 ± 0.013 in groups A, B and C, respectively. The means of EMPs were 0.15 ± 0.029, 0.056 ±  .013 and 0.014 ± 0.002 in groups A, B and C, respectively. There were significant differences between group C and groups A and B (p < 0.05 for each). This study clearly demonstrated that there is a significant association between LOH and the higher expression of EPCs and EMPs in patients with vasculogenic ED.

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis.

Studies have suggested that metformin can potentially decrease the incidence of cancer and improve survival outcomes. However, the association between metformin use and the incidence and survival of endometrial cancer (EC) remains controversial. So, a meta-analysis was performed. An electronic search was conducted using PubMed, EMBASE, and Web of Science. The outcome measures were relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) comparing the EC incidence and survival in patients treated with and without metformin. Eleven studies involving 766,926 participants were included in this study. In the pooled analysis of five studies which evaluated the association of metformin use with the incidence of EC, we found that metformin use was associated with a 13% reduction in EC risk among patients with diabetes (RR = 0.87, 95% CI: 0.80-0.95; p = 0.006). In the pooled analysis of six retrospective cohort studies evaluating the effect of metformin on the survival of EC patients, we found that, relative to nonuse, metformin use significantly improved the survival of EC patients (HR = 0.63, 95% CI: 0.45-0.87; p = 0.006). This study showed that metformin use was significantly associated with a decreased incidence of EC in diabetes and a favorable survival outcome of EC patients.

Be Careful What You Ask For: Effects of Benefit Descriptions on Diabetes Patients' Benefit-Risk Tradeoff Preferences.

As more studies report on patient preferences for diabetes treatment, identifying diabetes outcomes other than glycated hemoglobin (HbA1c) to describe effectiveness is warranted to understand patient-relevant, benefit-risk tradeoffs.

Cost-Effectiveness Analysis of Systemic Therapies in Advanced Pancreatic Cancer in the Canadian Health Care System.

To assess the cost-effectiveness of gemcitabine (G), G + 5-fluorouracil, G + capecitabine, G + cisplatin, G + oxaliplatin, G + erlotinib, G + nab-paclitaxel (GnP), and FOLFIRINOX in the treatment of advanced pancreatic cancer from a Canadian public health payer's perspective, using data from a recently published Bayesian network meta-analysis.

A Cost-Effectiveness Evaluation of Germline BRCA1 and BRCA2 Testing in UK Women with Ovarian Cancer.

To evaluate the long-term cost-effectiveness of germline BRCA1 and BRCA2 (collectively termed "BRCA") testing in women with epithelial ovarian cancer, and testing for the relevant mutation in first- and second-degree relatives of BRCA mutation-positive individuals, compared with no testing. Female BRCA mutation-positive relatives of patients with ovarian cancer could undergo risk-reducing mastectomy and/or bilateral salpingo-oophorectomy.

Subclinical inflammation associated with prolonged TIMP-1 upregulation and arterial stiffness after gestational diabetes mellitus: a hospital-based cohort study.

Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother. Some clinical studies have suggested subclinical inflammation and vascular dysfunction after GDM. We aimed to study whether concentrations of high-sensitivity C-reactive protein (hsCRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-8 (MMP-8) and -9, as well as values of arterial stiffness differ between women with and without a history of GDM a few years after delivery. We also investigated possible effects of obesity on the results.

Bioinformatics analysis to screen the key prognostic genes in ovarian cancer.

Ovarian cancer (OC) is a gynecological oncology that has a poor prognosis and high mortality. This study is conducted to identify the key genes implicated in the prognosis of OC by bioinformatic analysis.

Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis.

Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell-driven autoimmune disease caused by impaired central tolerance, are susceptible to chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop APECED-like phenotypes, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or autoreactive CD4 T cell depletion rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or epidermal growth factor receptor (EGFR) activity decreases fungal burden. Fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development.