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ObjectiveCardiovascular disease is the leading cause of morbidity and mortality in the USA. Thyroid analogs have emerged as a potential new therapeutic agent for cardiovascular disease. Thyroid hormones beneficially influence cardiac contractility and serum lipids but can also confer harmful effects

Nodular regenerative hyperplasia (NRH) and hepatoportal sclerosis, also known as obliterative portal venopathy (OPV), are two causes of non-cirrhotic portal hypertension (NCPH). NCPH is an increasingly recognized entity that can be seen in association with collagen vascular diseases and with the use of medications such as azathioprine and didanosine, but oftentimes the etiology remains unidentified. We herein report a case of NCPH occurring due to OPV and NRH in a 64-year-old woman with myasthenia gravis (MG), status post-thymectomy. Portal hypertension was diagnosed incidentally on computed tomography in the absence of predisposing factors. Extensive work-up to determine the etiology of any underlying liver disease was unrevealing. NRH and OPV were identified on liver biopsy. Subsequently, the patient had variceal bleeding that necessitated transjugular intrahepatic portosystemic shunt placement. A few similar cases of NCPH occurring in the setting of MG have been previously reported, suggesting that the immunological mechanisms involved in the pathogenesis of myasthenia may also have contributed to the development of NCPH.

Osteoporosis, a global health problem, is now frequently recognized to be secondary to alterations in the pituitary-bone axis. This review examines the current evidence for how dysregulation of the pituitary-bone axis leads to osteoporotic bone loss. Specifically, perimenopausal bone loss in the context of follicle-stimulating hormone action, and hyperthyroid bone loss in the context of thyroid-stimulating hormone action are explored. From the reviewed scientific findings, recommendations for early diagnosis and better clinical management of bone loss are made.

OBJECTIVES: Clostridium difficile infection (CDI) in the elderly has a higher prevalence, greater morbidity and mortality, and lower response to conventional treatment than the general population. Fecal microbiota transplant (FMT) is highly effective therapy for CDI but has not been studied specifically in the elderly. This study aims to determine the long-term efficacy and safety of FMT for recurrent (RCDI), severe (SCDI), and complicated (CCDI) CDI in elderly patients. METHODS: A multicenter, long-term follow-up study was performed with demographic, pre-FMT, and post-FMT data collected from elderly patients with RCDI, SCDI, and CCDI, through a 47-item questionnaire. Outcome measures included primary and secondary cure rates, early (

Background & Aims Our understanding of malignancy associated with immunosuppression in patients with inflammatory bowel disease (IBD) comes from studies of individuals with no history of cancer. We investigated whether patients with IBD and a history of cancer who were subsequently immunosuppressed have an increased risk of developing incident cancer. Methods We performed a retrospective analysis of data from 333 patients with IBD treated at 8 academic medical centers who developed cancer and subsequently received treatment with anti–tumor necrosis factor (TNF), anti-TNF with an antimetabolite (thiopurines, methotrexate), antimetabolites, or no subsequent exposure to immunosuppressive agents (controls). We collected data on their primary outcomes of incident cancers (new or recurrent). Hazard ratios (HRs) were calculated by using Cox proportional hazards and Kaplan-Meier survival curves; study groups were compared by using the log-rank test. Results During the follow-up period, 90 patients (27%) developed an incident cancer. Patient characteristics between groups differed, but matching was not possible because of the relatively small sample sizes. There was no difference in time to incident cancer ( P = .14) or type of incident cancer ( P = .61) among the 4 groups. After adjusting for recurrence risk for type of prior cancer, there was no difference in risk of incident cancer (HR for anti-TNF, 0.32; 95% confidence interval [CI], 0.09–1.09; HR for anti-TNF with an antimetabolite, 0.64; 95% CI, 0.26–1.59; HR for an antimetabolite, 1.08; 95% CI, 0.54–2.15) or time to subsequent cancer between study arms ( P = .22). Conclusion On the basis of a retrospective study, in patients with IBD and a history of cancer, exposure to an anti-TNF agent or an antimetabolite after cancer was not associated with an increased risk of incident cancer, compared with patients who did not receive immunosuppression. Larger, matched, prospective studies are needed to confirm these findings.

Nodular regenerative hyperplasia (NRH) and hepatoportal sclerosis, also known as obliterative portal venopathy (OPV), are two causes of non-cirrhotic portal hypertension (NCPH). NCPH is an increasingly recognized entity that can be seen in association with collagen vascular diseases and with the use of medications such as azathioprine and didanosine, but oftentimes the etiology remains unidentified. We herein report a case of NCPH occurring due to OPV and NRH in a 64-year-old woman with myasthenia gravis (MG), status post-thymectomy. Portal hypertension was diagnosed incidentally on computed tomography in the absence of predisposing factors. Extensive work-up to determine the etiology of any underlying liver disease was unrevealing. NRH and OPV were identified on liver biopsy. Subsequently, the patient had variceal bleeding that necessitated transjugular intrahepatic portosystemic shunt placement. A few similar cases of NCPH occurring in the setting of MG have been previously reported, suggesting that the immunological mechanisms involved in the pathogenesis of myasthenia may also have contributed to the development of NCPH.

Pituitary hormones orchestrate the structure and function of various organ systems in the body. A specific, limited function is ascribed to each pituitary hormone. We have come to appreciate that pituitary hormones have profound effects on bone, so much so that the “pituitary-bone axis” is now understood to be integral to skeletal biology. All pituitary hormones play a part in bone regulation, including growth hormone (GH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), prolactin and oxytocin. In mice, reduction in hormone levels due to haploinsufficiency for any one of several pituitary hormones or their receptors alters bone dynamics, while the “primary” target organ remains unaffected. This finding indicates that bone is the more sensitive organ. An in-depth insight into the mechanism of action of each hormone gives us a better understanding of bone pathophysiology and opens up new avenues for treatment of osteoporosis. In this chapter, we discuss the interaction of each pituitary hormone with bone and the potential that targeting these interactions holds in management of osteoporosis.

Osteoporosis is a leading cause of morbidity in patients with inflammatory bowel disease (IBD). Bone loss is an early systemic process and occurs even before clinical disease manifests. Bone disease is attributed to vitamin D deficiency, steroid use, and/or systemic inflammation. In this review, we discuss the molecular pathways of bone loss mediated by inflammatory cytokines and other mediators. Further research will hopefully clarify the mechanisms of inflammation-induced bone loss in IBD and guide effective treatment modalities.

In nonneuronopathic type 1 Gaucher disease (GD1), mutations in the glucocerebrosidase gene (GBA1) gene result in glucocerebrosidase deficiency and the accumulation of its substrate, glucocerebroside (GL-1), in the lysosomes of mononuclear phagocytes. This prevailing macrophage-centric view, however, does not explain emerging aspects of the disease, including malignancy, autoimmune disease, Parkinson disease, and osteoporosis. We conditionally deleted the GBA1 gene in hematopoietic and mesenchymal cell lineages using an Mx1 promoter. Although this mouse fully recapitulated human GD1, cytokine measurements, microarray analysis, and cellular immunophenotyping together revealed widespread dysfunction not only of macrophages, but also of thymic T cells, dendritic cells, and osteoblasts. The severe osteoporosis was caused by a defect in osteoblastic bone formation arising from an inhibitory effect of the accumulated lipids LysoGL-1 and GL-1 on protein kinase C. This study provides direct evidence for the involvement in GD1 of multiple cell lineages, suggesting that cells other than macrophages may be worthwhile therapeutic targets.

The use of antiretroviral therapy has significantly reduced the number of deaths due to HIV/AIDS. However, no current therapy can suppress the virus completely, and as the HIV-infected population continues to live longer new complications are emerging from the persistence of the virus and use of antiretroviral therapy. This review summarizes the clinical evidence linking HIV-associated osteoporosis to direct infection and antiretroviral therapy (ART) use. The purported molecular mechanisms involved in bone loss are also reviewed. Additionally, recommendations regarding the pharmacologic management of HIV/ART-related osteoporosis are given.

Palatine and nasopharyngeal tonsils are lymphatic flesh clusters of tissue of the respiratory and digestive tract's epithelium. There is not much literature pertaining to the histological assessment of resected tonsils though anecdotal case reports of choristoma, squamous cell cysts of the tonsil have been reported which mimicked chronic tonsillitis. Tonsils also are an important site for head and neck cancer in adults. AIM #ENTITYSTARTX00026;To study the histological features of routine tonsillectomy specimens and to study for the presence of choristomatic tissue or any other benign pathology as a cause of chronic tonsillitis. PATIENTS #ENTITYSTARTX00026;Fifty consecutive tonsillectomy specimens, which were received in the department of Pathology, Gandhi Medical College, were evaluated with regards to clinical information. Among 50 patients, a slight predominance of men (56 %) over women (44 %) was observed.The mesenchymal tissue consisted mainly of epithelium and lymphoid tissue with cartilage in a single case and fat in three cases. The role of imaging techniques, in assessing the need for early surgical intervention in cases with chronic tonsillitis, can be determined by assessing the micropathology of tonsillectomy specimens and is an arena for further research. We discussed the role of FDG-PET scan in the assessment of the same.

Back ground: The calcineurin inhibitor (CNI) tacrolimus (TAC) has been reported to be effective for induction and maintenance of remission in patients with refractory ulcerative colitis (UC). However, CNI has nephrotoxic potential leading to acute and chronic renal damage in some cases. To date, little is known about the influence of long term administration of oral TAC on renal function in patients with UC. Aim: The aim of our study was to evaluate the incidence and the severity of renal function impairment in UC patient who received TAC treatment. Methods: In this retrospective study, the medical charts of 71 adult patients with steroid-refractory UC treated with TAC between 2012 and 2014 in a single Japanese center were analyzed. In principle, TAC was orally administrated as a 2 week-induction (target trough levels 10-15ng/ml) followed by a maintenance therapy (target trough levels 5-10ng/ml). Estimated glomerular filtration rate (eGFR) was evaluated during the treatment. Acute kidney injury (AKI) was defined by the RIFLE (Risk of renal dysfunction, Injury to the kidney, Failure of function, Loss of function and End-stage kidney disease) consensus criteria using the maximal change in serum creatinine (Scr) and eGFR during the TAC treatment compared with baseline value before treatment. Results: The mean duration of TAC administration was 210 days. At 12weeks, TAC produced a clinical response in 54 patients (76.1%) and remission was achieved in 29 of those 54 (40.8%). The AKI rate during TAC treatment was 46.5% (33 of 71 patients). RIFLE class R (Scr increase > 1.5 times or eGFR decrease > 25%) accounted for 27 patients (38.0%), and RIFLE class I (Scr increase > 2 times or eGFR decrease > 50%) for six (8.5%). The AKI rate was 76.8% (10/13) in patients who had been administrated TAC for more than 1 year and 37.5% (18/48) in patients with TAC treatment within 6 months (p=0.006). After withdrawal of TAC, renal function impairment (eGFR decrease > 25%) was still observed in 10 patients (14.1%). Conclusions: Oral TAC therapy appears to be effective for patients with refractory UC. However, renal function impairment was frequently observed during this treatment. Thus, careful monitoring of renal function must be required to avoid irreversible chronic renal damage during long-term administration of TAC.

Background/Purpose: Childhood obesity is a growing epidemic in the United States. However, healthcare providers, including medical students and residents, do not feel prepared to diagnose obesity, perform counseling, or treat obesity and its complications. The purpose of this study is to design a web-based module to adequately deliver educational content pertinent to medical students on the topic of pediatric obesity. The effectiveness of the module was evaluated in terms of content mastery and overall satisfaction using a pre-test, post-test, and post-test survey. We hypothesize that there will be a significant increase in knowledge on key content areas related to the topic of pediatric obesity after viewing the web-based module. Methods: An IRB approved, prospective study of 217 third year U.S. medical students was performed. Students were given a pre-test followed by educational content delivered in the form of a web-based module, then a post-test. Test questions centered on areas of the assessment, evaluation, counseling, treatment, and complications of pediatric obesity. Participants served as their own controls to compare pretest and posttest scores. Overall satisfaction with both the content and method of delivery of the web-based module was assessed using a post-test survey. Results: Completing the web-based module resulted in improved scores when comparing post-test to pre-test scores. Average scores increased from 77.4% correct on the pre-test to 93.6% on the post-test, an overall 16.2% increase in content mastery (95% CI 13.9-18.5, p