Type 2 Diabetes Medication and Cardiovascular Benefits.

Diabetes mellitus remains one of the most common and disabling diseases in the world. Patients with diabetes tend to have more cardiovascular complications, regardless of their prior cardiac history. Tight glycemic control has been shown to prevent microvascular complications as it relates to nephropathy and retinopathy; however, it hasn't been proven beneficial in patients with macrovascular diseases, i.e., cardiovascular disease. In fact, two groups of diabetic medications, dual peroxisome-proliferator-activated receptor - agonists and sulfonylurea, are known to worsen cardiovascular disease. Patients using this group of medications have shown increased heart failure readmission rates and increased risk for cardiovascular death. Insulin and Metformin have been the gold standard treatment for diabetes management to prevent worsening cardiac outcomes, and now a newer class of medications have demonstrated similar results. These drug classes includes sodium glucose cotransporter 2(SGLT 2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon like peptide-1 (GLP 1) analogues.

Candida Dubliniensis Tricuspid Valve Endocarditis.

Infective endocarditis is a common complication in patients using intravenous drugs. Fungal endocarditis is a rare clinical entity and diagnosis are often delayed. Only a few cases of candida dubliniensis have been reported in the literature so far. These cases usually present in patients with a history of intravenous drug abuse. If a patient with valvular endocarditis continues to have fever despite antibiotics, then fungal infection should be suspected. Fungal endocarditis is usually treated surgically along with a prolonged course of antifungal treatment. We report an interesting case of a young female who initially presented with fever and chills and was subsequently found to have a significantly large tricuspid mass. Upon further study it was found to be of fungal origin which was later confirmed by biopsy cultures.

Management of Antiplatelet Agents in Patients with History of Coronary Artery Disease in Various Medical Conditions.

Antiplatelet agents are the mainstay of treatment for patients with acute coronary syndrome (ACS) or stable ischemic heart disease (SIHD). The most commonly used antiplatelet agents are aspirin and clopidogrel. Newer agents such as ticagrelor are becoming more commonplace as new studies have shown more cardiovascular benefits with these group of medications. The duration of use of these agents in setting of stable disease versus ACS is variable. We have tried to delineate the usage and duration of these agents in patients with the history of ACS or SIHD in numerous medical conditions. We have delved into available guidelines from American College of Cardiology/American Heart Association, Society of Thoracic Surgeons, and American College of Gastroenterology for our review article.

Pulmonary Hypertension: Brief Review Article.

Pulmonary hypertension (PH) is defined as mean pulmonary artery pressure (mPAP) 25 mmHg or greater at rest; this measurement is obtained during right heart catheterization. The exact prevalence of PH in the U.S. is unknown. Advances in hemodynamic studies of the right heart side and pulmonary circulations has helped improve our understanding of this condition. This better understanding aids the development of treatment agents aimed at improving quality of life, morbidity and mortality. Awareness of this condition and understanding the classification of PH and the available treatment modalities is crucial hence we aim to briefly review the classification, diagnosis and treatment of PH in this article.

Statins and Abnormal Liver Enzymes.

Statins are a group of essential medications used in ischemic heart disease, stroke, and peripheral vascular disease. In patients with these medical conditions, they have been proven to decrease mortality and morbidity. However, statins can cause transient elevation of liver enzymes in some patients, which has led to the unnecessary cessation of these agents prematurely. Physicians also face a dilemma when determining if they should utilize statins in patients whose liver enzymes are elevated at baseline. This dilemma may prevent physicians from prescribing statins when clinically indicated, and safe. The purpose of this article is to review existing literature that provides guidance on the utilization of statins in clinical scenarios where liver enzymes are elevated at baseline or when liver enzymes increase after the initiation of statin-based therapy.

An Unusual Case of GI Bleeding: Could Histolasmosis be the Culprit?

Gastrointestinal (GI) histoplasmosis is a rare disease with variable manifestations. We report a case of a male patient who developed disseminated histoplasmosis with prominent manifestations of GI bleeding, and esophagogastroduodenoscopy and colonoscopy revealed atypical ulcers. With the treatment of itraconazole, patient's GI bleeding stopped, and follow up endoscopies revealed resolution of the ulcers.

Keratins regulate ß-cell mitochondrial morphology, motility, and homeostasis.

Loss of the epithelial intermediate filament protein keratin 8 (K8) in murine ß cells leads to irregular insulin vesicles and decreased insulin levels. Because mitochondria are central in glucose-stimulated insulin secretion, the relationship between keratins and ß-cell mitochondrial function and morphology was investigated. ß cells in murine K8-knockout (K8-/-) islets of Langerhans have increased numbers of mitochondria, which are rounder and have diffuse cristae, as seen by electron microscopy. The mitochondrial network in primary cultured K8-/- ß cells is more fragmented compared with K8+/+ mitochondria, correlating with decreased levels of mitofusin 2 and the mitofusin 2- and keratin-binding protein trichoplein. K8-/- ß-cell mitochondria have decreased levels of total and mitochondrial cytochrome c, which correlates with a reduction in electron transport complexes I and IV. This provokes loss of mitochondrial membrane potential and reduction of ATP and insulin amount, as seen in K8-/- ß cells. Mitochondria in K8 wild-type ß cells and MIN6 insulinoma cells overexpressing K8 and 18 are more stationary compared with mitochondria in keratin-deficient cells. In conclusion, keratins, likely through trichoplein-mitofusin interactions, regulate both structural and dynamic functions of ß-cell mitochondria, which could have implications for downstream insulin secretion.-Silvander, J. S. G., Kvarnström, S. M., Kumari-Ilieva, A., Shrestha, A., Alam, C. M., Toivola, D. M. Keratins regulate ß-cell mitochondrial morphology, motility, and homeostasis.

Prosthetic Aortic Valve Endocarditis Following Transcatheter Aortic Valve Implantation.

Infective endocarditis after transcatheter aortic valve implantation is a life-threating complication, resulting in high in-hospital and one-year mortality. With the ongoing evolution of transcatheter aortic interventions, the proportion of endocarditis cases encountered by health care providers will continue to rise. Early diagnosis of infective endocarditis is of paramount importance to institute appropriate treatment with antibiotics and/or surgery to avoid negative clinical outcomes. In this review, we outline our experience with two cases of infective endocarditis following transcatheter aortic valve implantation and briefly review the literature on the incidence, microbiology, diagnosis, and management of this condition.

Critical Role of AMPK/FoxO3A Axis in Globular Adiponectin-Induced Cell Cycle Arrest and Apoptosis in Cancer Cells.

Adiponectin predominantly secreted from adipose tissue has exhibited potent anti-proliferative properties in cancer cells via modulating cell cycle and apoptosis. FoxO3A, a Forkhead box O member of the transcription factor, plays a critical role in modulating expression of genes involved in cell death and/or survival. In this study, we investigated the role of FoxO3A signaling in anti-cancer activities of adiponectin. Herein, we have shown that treatment with globular adiponectin (gAcrp) increases p27 but decreases cyclinD1 expression in human hepatoma (HepG2) and breast (MCF-7) cancer cells. Gene ablation of FoxO3A prevented gAcrp-induced increase in p27 and decreased in cyclin D1 expression, and further ameliorated cell cycle arrest by gAcrp, indicating a critical role of FoxO3A in gAcrp-induced cell cycle arrest of cancer cells. Moreover, treatment with gAcrp also induced caspase-3/7 activation and increased Fas ligand (FasL) expression in both HepG2 and MCF-7 cells. Transfection with FoxO3A siRNA inhibited gAcrp-induced caspase-3/7 activation and FasL expression, suggesting that FoxO3A signaling also plays an important role in gAcrp-induced apoptosis of cancer cells. We also found that gene silencing of AMPK prevented gAcrp-induced nuclear translocation of FoxO3A in HepG2 and MCF-7 cells. In addition, suppression of AMPK also blocked gAcrp-induced cell cycle arrest and further attenuated gAcrp-induced caspase-3/7 activation, indicating that AMPK signaling plays a pivotal role in both gAcrp-induced cell cycle arrest and apoptosis via acting as an upstream signaling of FoxO3A. Taken together, our findings demonstrated that AMPK/FoxO3A axis plays a cardinal role in anti-proliferative effect of adiponectin in cancer cells.

What do women with gynecologic cancer know about HPV and their individual disease? A pilot study.

BACKGROUND: The vaccinations against human papilloma virus (HPV) are highly effective in preventing persistent infection. The level of knowledge about HPV and the consequences of an infection with this virus are low in the general population and in patients who suffer from HPV-associated diseases. We aimed to compare the level of knowledge about HPV and about the women's individual malignant disease between women with and without HPV-associated gynecologic cancer as well as the knowledge about individual malignant diseases. METHODS: In a pilot study, 51 women with HPV-related cancer (cervical cancer: n=30; vulvar or vaginal cancer: n=21) and 60 women with non-HPV associated gynecologic malignancies (ovarian cancer: n=30; endometrial cancer, n=30) were included. They answered a questionnaire including questions about personal medical history, risk factors for cancer development, and HPV. RESULTS: The general level of knowledge of the term "HPV" was low (29.7%, 33/111) and it was similar in patients with HPV-related and non-HPV-associated cancer (18/60, 30.0% vs. 15/51, 29.4%, respectively; p=1.000). When asked about their disease, 80% (24/30) of women with ovarian cancer correctly named their diagnosis, followed by women with cervical cancer (73.3%, 22/30), endometrial cancer (70%, 21/30) and vaginal or vulvar cancer (42.9%, 9/21; p=0.008). CONCLUSION: The level of knowledge about HPV and the malignant diseases the patient suffered from was low. This applied even to patients with HPV associated malignancies.

Safety and Quality Within the Healthcare Supply Chain: A Great Unknown.

Quality and safety in healthcare have emerged as key factors impacting on both clinical effectiveness and clinical outcomes. While improving the healthcare supply chain has been extensively researched, the impact of the healthcare supply chain on clinical safety has received little attention in the literature, largely due to the complexity of such studies and the involvement of multiple stakeholders. This research proposes an evaluation model using key performance measurements for an electronic procurement system that enables digital transformation of the healthcare supply chain. The model will be tested before and after the introduction of an electronic procurement system in the healthcare supply chain for small and medium sized healthcare providers to provide evidence of both the usefulness of the model itself within industry and to further contribute to the knowledge base. Future use of the model may provide benchmarking and important data and insights to enable enhanced clinical safety in the healthcare supply chain.

Complete androgen insensitivity syndrome diagnosed after inguinal surgery in era of modern technology: a case report.

Introduction: Androgen Insensitivity Syndrome (AIS) is a rare X-linked recessive disorder of sexual development. It results from mutations in the Androgen Receptor (AR) gene located on chromosome Xq11-12. Affected individuals have a male genotype but a female phenotype. Case presentation: A 20-year-old female presented to the emergency room with a history of pain in the bilateral inguinal region. In ultrasonography (USG), bilateral inguinal hernia was suspected. While performing an emergency operation for hernia repair, hernia was revealed as bilateral abdominal testis. Then, after a gynecology consultation, a bilateral orchidectomy was done. Postoperative karyotyping showed a male genotype. Then the patient was discharged on hormone replacement therapy to maintain normal bone mineral density and secondary sexual characteristics. Discussion: AIS presents with primary amenorrhea in pubertal females. The growth spurt and secondary sexual characteristics are normal except for absent axillary and pubic hair. There is a short-blind vagina, but the uterus is absent, and the abdominal testis presents as an inguinal hernia. Serum gonadotropin level, karyotyping, and imaging studies are done to reach a diagnosis. Management includes gonadectomy, genitoplasty, and hormone replacement therapy. Conclusion: The objective of this report was to make clinicians aware that AIS can present as a bilateral inguinal hernia. In acute presentations, it can be misdiagnosed as a strangulated femoral hernia only later to be identified as an undescended abdominal testis during surgery. An absence of proper clinical judgment and reliance on USG for imaging can often lead to misdiagnosis in acute settings.

Tuberous Sclerosis Complex in a 17-month-old: A Case Report.

Tuberous sclerosis complex is a rare autosomal dominant genetic disorder that affects multiple organ systems, primarily affecting the central nervous system. It develops with a pathogenic mutation in tumour suppressor genes i.e. Tuberous Sclerosis Complex 1 or Tuberous Sclerosis Complex 2 which codes for protein hamartin and tuberin leading to unopposed hyperactivation of the mammalian target of the rapamycin signalling pathway. It presents with a triad of facial angiofibroma, intellectual disability, and epilepsy. We present a case of a 17-month female toddler with abnormal body movement with loss of consciousness and later developing into generalised jerky movements. On magnetic resonance imaging, a diagnosis of tuberous sclerosis was made. The patient underwent symptomatic management with anti-epileptic. As seizures in these cases are subtle, they remain undiagnosed for a long time leading to delays in management and developing refractory seizures. Keywords: angiofibroma; case reports; seizures; tuberous sclerosis; tumor suppressor gene.

Utility of the Parkland Grading Scale to determine intraoperative challenges during laparoscopic cholecystectomy: a validation study on 206 patients at an academic medical center in Nepal.

BACKGROUND: Most of the scoring systems to predict difficult laparoscopic cholecystectomy are based on pre-operative clinical and radiological findings. Recently the Parkland Grading Scale system was introduced as a simple intra-operative grading scale. This study aims to utilize the Parkland Grading Scale system to assess the intraoperative challenges during laparoscopic cholecystectomy. METHOD: This was a prospective, cross-sectional study done at Chitwan Medical College and Teaching Hospital, Chitwan, Nepal. All the patients underwent laparoscopic cholecystectomy from April 2020 to March 2021. Based on the initial intra-operative finding, Parkland Grading Scale was noted and at the end of the surgery, the level of difficulty was given by the operating surgeon. All the pre-operative, intra-operative, and post-operative findings were compared with the scale. RESULTS: Out of 206 patients, there were 176 (85.4%) females, and 30 (14.6%) males. The median age was 41 years (Range 19-75). The median body mass index was 23.67 kg/m2. There were 35(17%) patients with a history of previous surgery. The rate of conversion to open surgery was 5.8%. According to Parkland Grading Scale, 67(32.5%), 75(36.4%), 42(20.4%), 15(7.3%), and 7(3.4%) were graded as grade 1, 2, 3, 4, and 5 respectively. There was a difference in the Parkland grading scale in patients with a history of acute cholecystitis, gallbladder wall thickness, pericholecystic collection, stone size, and body mass index (p < 0.05). The total operative time, level of difficulty in surgery, rate of help needed from colleagues or replacement as the main surgeon, bile spillage, drain placement, gallbladder decompression, and conversion rate all increased with an increase in scale (p < 0.05). There was a significant increase in the development of post-operative fever, and post-operative hospital stay as the scale increased (p < 0.05). The Tukey-Kramer test for all pair-wise comparisons revealed that each grade was significantly different from each other (p < 0.05) on the difficulty of surgery except for grade 4 from 5. CONCLUSION: Parkland Grading Scale system is a reliable intra-operative grading system to assess the difficulty in laparoscopic cholecystectomy and helps the surgeon to change the strategy of surgery. An increase in scale is associated with an increased difficulty level of the surgery.