Cardiovascular Outcomes of Hypogonadal Men Receiving Testosterone Replacement Therapy: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To investigate the impact of testosterone replacement therapy (TRT) on cardiovascular outcomes in hypogonadal men. METHODS: A meta-analysis of 26 randomized controlled trials involving 10 941 participants was conducted. Various clinical outcomes, including all-cause mortality, cardiovascular-related mortality, myocardial infarction, stroke, congestive heart failure, atrial fibrillation, pulmonary embolism, and venous thrombosis, were assessed. RESULTS: No statistically significant differences were observed between the TRT group and the control group in terms of these clinical outcomes. Sensitivity analysis and publication bias assessment supported the robustness of the findings. Meta-regression analysis found no significant associations between clinical outcomes and potential covariates, including age, diabetes, hypertension, dyslipidemia, and smoking. DISCUSSION: Previous research on TRT and cardiovascular events, with comparisons to studies like the Testosterone Trials and the studies conducted by Vigen et al, Finkle et al, Layton et al, and Wallis et al, is provided. The significance of the systematic review and meta-analysis approach is emphasized, particularly its exclusive focus on hypogonadal patients. CONCLUSION: This study offers reassurance that TRT does not increase mortality risk or worsen cardiovascular outcomes in hypogonadal men. However, further research, especially long-term studies involving diverse populations, is essential to strengthen the evidence base and broaden the applicability of these findings.

Renal Cell Carcinoma Metastases to Thyroid and Pancreas: A Rare Occurrence.

OBJECTIVE: To report on a case of late metastases of clear cell renal carcinoma to the thyroid and pancreas. METHODS: A 51-year-old female with a history of nephrectomy 15 years prior for renal cell carcinoma presented with new metastases in the thyroid and pancreas, which were surgically excised. RESULTS: Pathology noted that both lesions were clear cell carcinomas, and the immunohistochemistry was consistent with metastases from clear cell renal carcinoma. CONCLUSION: 1) Renal cell carcinoma can present late metastases to unusual organs like the thyroid and pancreas. 2) A prior history of renal cell carcinoma should raise suspicions of metastases when evaluating a thyroid or pancreatic mass. 3) An ultrasound-guided fine needle aspiration biopsy of the thyroid may not be diagnostic. 4) The treatment of choice is surgical resection.

Clinical Outcomes of a Team Approach to Thyroidectomy.

OBJECTIVE: The aim of this study is to assess the rates of thyroidectomy complications performed by two attending surgeons operating together. STUDY DESIGN: This is a retrospective chart review. METHODS: This is a retrospective chart review from September 2008 through October 2013 of thyroidectomy cases performed by the head and neck team at Sanford Health. The primary intervention was the presence of two head and neck attendings during each procedure. Outcomes assessed include rates of temporary and permanent recurrent laryngeal nerve paralysis, and of permanent hypocalcemia. RESULTS: There were 282 patients that underwent a thyroid procedure with a total of 449 at-risk nerves. There were five (1.1 percent) cases of transient vocal cord paresis. There was one case (0.22 percent) of permanent vocal cord paresis after planned nerve resection in a patient with anaplastic thyroid carcinoma. There were no other cases of permanent vocal cord paresis. Of 156 total thyroidectomy cases, there was one case of chronic hypocalcemia (0.64 percent). CONCLUSIONS: A two-surgeon approach to thyroidectomy produces excellent functional outcomes. Further investigation into cost-effectiveness is warranted.

Revolutionizing diabetes care: unveiling tirzepatide's potential in glycemic control and beyond.

INTRODUCTION: Diabetes is a global public health challenge with rising prevalence. This review explores current diabetes understanding, diagnostic and management guidelines, economic impact, and lifestyle modifications as the primary approach. AREAS COVERED: Focusing on pharmacological interventions, we discuss the roles of GLP-1 agonists and GLP/GIP agonists in diabetes management and cardiovascular risk reduction. Tirzepatide, a novel medication, is highlighted for its unique mechanism of action. Clinical trials demonstrate its effectiveness in glucose control, weight reduction, and its potential impact on diabetes, obesity, NASH, and cardiovascular risks. EXPERT OPINION: Tirzepatide shows promise in diabetes treatment, offering glucose control and weight loss. It also holds potential for addressing comorbidities. However, cautious use is vital due to potential adverse effects and contraindications, including hypersensitivity reactions, pregnancy, and breastfeeding precautions. This review underscores tirzepatide as a valuable addition to diabetes therapies, with evolving prospects for enhanced patient outcomes as research advances.

Comparative Analysis of Clinical Outcomes of High-power, Short-duration Ablation versus Low-power, Long-duration Ablation Strategy in Patients with Atrial Fibrillation: A Comprehensive Umbrella Review of Meta-analyses.

Atrial fibrillation (AF) affects around 33 million people worldwide, rendering it a common cardiac arrhythmia. Catheter ablation (CA) has evolved as a leading therapeutic intervention for symptomatic AF. This umbrella review systematically evaluates existing systematic reviews and meta-analyses to assess the safety, efficacy, and potential of high-power, short-duration (HPSD) ablation as an alternative therapy option for AF. A thorough exploration was undertaken across PubMed, the Cochrane Library, and Embase to identify pertinent studies for inclusion in this umbrella review. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was employed to assess the overall certainty of the evidence comprehensively, and the quality of the incorporated reviews was meticulously evaluated through use of the AMSTAR 2 tool, the Cochrane Collaboration tool, and the Newcastle-Ottawa scale. In this study, we initially identified 35 systematic reviews and meta-analyses, narrowing them down to a final selection of 11 studies, which collectively integrated data from 6 randomized controlled trials and 26 observational studies. For primary efficacy outcomes, the HPSD approach led to a non-significant decrease in the risk of atrial tachyarrhythmia recurrence (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.70-1.12; I 2 = 90%; P = .31) and a significantly reduced risk of AF recurrence (RR, 0.53; 95% CI, 0.42-0.67; I 2 = 0%; P < .00001) compared to the low-power, long-duration (LPLD) approach. In terms of primary safety outcomes, the HPSD approach significantly reduced the risk of esophageal thermal injury (ETI) (RR, 0.71; 95% CI, 0.61-0.83; I 2 = 0%; P < .00001) and facilitated a non-significant decrease in the risk of other major complications (RR, 0.87; 95% CI, 0.73-1.03; I 2 = 0%; P = .10). In conclusion, HPSD therapy is safer and more effective than LPLD therapy, facilitating decreased AF recurrence rates along with reductions in ETI, total procedure duration, ablation number, ablation time, fluoroscopy time, and acute pulmonary vein reconnection.

Ipilimumab immune-related adverse reactions: a case report.

Ipilimumab is an immunomodulating agent approved by the Food and Drug Administration (FDA) as of March 2011 for the treatment of metastatic melanoma. The medication works by inhibiting cytotoxic T-lymphocyte antigen 4, which typically works to down-regulate the T-cell response and protects self-antigens from recognition by the immune system. Since the T-cells are no longer down-regulated by this antigen, they are allowed to proliferate, thereby helping to prevent melanoma tumor evasion. As a result of the up-regulation of the immune system, numerous immune-mediated adverse effects have been reported including colitis, dermatitis, hepatitis and rarely hypophysitis. Typically, these effects are treated with high-dose steroids and most eventually resolve. We present a case of autoimmune (lymphocytic) hypophysitis following treatment with four doses of ipilimumab 3mg/kg and discuss the work-up, treatment and prognosis of the event.

Ketosis-resistant diabetes: a rare case in unlikely territory.

BACKGROUND: Ketosis-resistant diabetes is a syndrome that has undergone numerous classification schemes in the past. In 1979, the National Diabetes Data Group (NDDG) introduced an association of malnutrition and diabetes. In 1985, the World Health Organization (WHO) created a new diabetes category called malnutrition-related diabetes mellitus (MRDM). MRDM consisted of two subclasses: fibrocalculous pancreatic diabetes (FCPD) and protein-deficient pancreatic diabetes (PDPD). Ketosis-resistant diabetes of the young (KRDY) was included in the subclass of PDPD. We report a rare case of a 37-year-old Sudanese immigrant with ketosis-resistant diabetes. CASE: A previously healthy 37-year-old male presented with increased lethargy, polydipsia, polyuria and weight loss for the last seven to eight months. The patient had immigrated to the U.S. from his native country of Sudan about seven years earlier. He was hemodynamically stable. Physical exam was unremarkable with no evidence of retinopathy or neuropathy. Initial laboratory findings revealed a random blood sugar of 1,409 mg/dl and hemoglobin A1C of 17.8 percent. Urinalysis showed negative proteinuria, positive glycosuria, but only trace ketones were detected. Interestingly, the patient's serum ketones were negative. Arterial blood gas revealed PH 7.37, PCO2 47, P02 108 and HCO3 27. Further diagnostic workup revealed C-peptide 0.36, insulin antibodies less than 2, glutamic acid decarboxylase (GAD) antibodies less than 0.5, ICA 512 antibodies 2.9 and negative anti-islet cell antibodies. An abdominal ultrasound did not show any evidence of pancreatic calcifications or any pathology. Aggressive fluid resuscitation and intravenous insulin was initiated. The patient's hospital course was uncomplicated. He responded well to intravenous insulin drip and hydration. He was eventually transitioned to subcutaneous insulin. He was discharged three days later on a home regimen that included Lantus 28 units SQ at night, Novolog 8 units SQ with meals and a sliding scale with Novolog as needed. The patient's recent follow-up appointment revealed adequate glycemic control with HbA1C level of 7 percent. CONCLUSION: Our patient did not meet criteria for either type 1 or type 2 diabetes mellitus. After a literature review of atypical etiologies of diabetes and comparing them to our patient, we concluded that the most likely diagnosis was KRDY. In light of a high influx of refugees and immigrants to the U.S., we should entertain. KRDY and other rare causes of diabetes mellitus in patients not satisfying criteria of either type 1 or type 2 diabetes.

A Review of Clinical Studies Assessing the Therapeutic Efficacy of Escitalopram: A Step Towards Development.

BACKGROUND: Major depression is a debilitating, sometimes fatal disorder, deteriorating the quality of life and well-being. Escitalopram showed highly selective and dose-dependent inhibitory activity on human serotonin transport. Selective serotonin reuptake inhibitors (SSRIs) are the first-line drugs to manage major depressive disorder (MDD). OBJECTIVE: The objective of this study is to explore the therapeutic potential of escitalopram, a clinically approved drug to manage MDD and panic disorders. METHODS: It emphasizes comparative and clinical trial studies with several pharmacological targets reviewed from the data available on PubMed, Science Direct, Clinicaltrails.gov, and from many reputed foundations. RESULTS: To highlight the clinical efficacy, safety, recent development, and stable formulation of escitalopram with an increased bioavailability profile. Evidence-based on the available clinical and pharmacoeconomic data, escitalopram represents an effective first-line treatment option for MDD patients. CONCLUSION: The present review highlights the placebo-controlled clinical studies and the recent development that can be helpful for further research perspectives.

Formulation, Development, and in-vitro Evaluation of Escitalopram Fast Dissolving Tablets.

BACKGROUND: Escitalopram, a selective serotonin reuptake inhibitor (SSRI), acts by increasing the serotonin level in the brain and is used widely for the management of depression and anxiety disorders. However, the poor dissolution rate of escitalopram due to less water solubility is a consequential problem confronting the pharmaceutical industry in developing pharmaceutical dosage forms for oral delivery systems. OBJECTIVE: The present work aims to deliver a novel formulation for improving the dissolution profile and, thus, the bioavailability of escitalopram. METHODS: Fast Dissolving Tablets (FDT) are expected to enable quick drug release, which will improve the drug's dissolving profile, allowing for the initial increase in plasma concentration mandatory in an acute depression attack. The use of co-processed excipients in tablets has been shown to increase the compressibility and disintegration properties of the tablets, resulting in improved in-vitro drug release and bioavailability. As co-processed excipients, a mixture of banana powder (a natural super disintegrant with nutritional value) and microcrystalline cellulose (a highly compressible substance with good wicking and absorption capacity) was used. RESULTS: The tablets were made using a response surface, randomised central composite design, and a direct compression technique. The manufactured tablets were found to be released more than 95% of the drug within 10 minutes and showed an improved drug release profile than the available marketed formulation. CONCLUSION: After confirming in-vivo potential, the fast release formulation exhibited impressive in-vitro findings and may prove to be a boon in treating acute depression attacks.

Hypogonadotrophic hypogonadism in type 2 diabetes, obesity and the metabolic syndrome.

Recent work shows a high prevalence of low testosterone and inappropriately low LH and FSH concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity, and other features of the metabolic syndrome (obesity and overweight, hypertension and hyperlipidemia) in patients with type 2 diabetes. However, the duration of diabetes or HbA1c were not related to HH. Furthermore, recent data show that HH is also observed frequently in patients with the metabolic syndrome without diabetes but is not associated with type 1 diabetes. Thus, HH appears be related to the two major conditions associated with insulin resistance: type 2 diabetes and the metabolic syndrome. CRP concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and CRP concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations in type 2 diabetic men have also been related to a significantly lower hematocrit and thus to an increased frequency of mild anemia. Low testosterone concentrations are also related to an increase in total and regional adiposity, and to lower bone density. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates symptoms related to sexual dysfunction, and features of the metabolic syndrome, insulin resistance and inflammation.

Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes.

OBJECTIVE: After the demonstration that one-third of male patients with type 2 diabetes have hypogonadotrophic hypogonadism, we have shown that patients with hypogonadotrophic hypogonadism also have markedly elevated C-reactive protein (CRP) concentrations. We have now hypothesized that type 2 diabetic subjects with hypogonadotrophic hypogonadism may have a lower hematocrit because testosterone stimulates, whereas chronic inflammation suppresses, erythropoiesis. RESEARCH DESIGN AND METHODS: Seventy patients with type 2 diabetes at a tertiary referral center were included in this study. RESULTS: The mean hematocrit in patients with hypogonadotrophic hypogonadism (n = 37), defined as calculated free testosterone (cFT) of <6.5 ng/dl, was 40.6 +/- 1.1%, whereas that in eugonadal patients (n = 33) was 43.3 +/- 0.7% (P = 0.011). The hematocrit was related to cFT concentration (r = 0.46; P < 0.0001); it was inversely related to plasma CRP concentration (r = 0.41; P < 0.0004). Patients with CRP <3 mg/l had a higher hematocrit (42.7 +/- 0.7%) than those with CRP >3 mg/l (39.9 +/- 1.1%; P < 0.05). The prevalence of normocytic normochromic anemia (hemoglobin <13 g/dl) was 23% in the entire group, whereas it was 37.8% in the men with hypogonadotrophic hypogonadism and 3% in the eugonadal men (P < 0.01). Erythropoietin concentration was elevated or high normal in all 11 patients with anemia in whom it was tested. CONCLUSIONS: We conclude that hypogonadotrophic hypogonadism in male type 2 diabetic subjects is associated with a lower hematocrit and a frequent occurrence of mild normocytic normochromic anemia with normal or high erythropoietin concentrations. In these patients, hematocrit is also inversely related to CRP concentration. Thus, low testosterone and chronic inflammatory mechanisms may contribute to mild anemia. Such patients may also have a high risk of atherosclerotic cardiovascular events in view of their markedly elevated CRP concentrations.

Insulin resistance and PPAR insulin sensitizers.

Drugs that reverse insulin resistance are of importance as insulin resistance is frequently associated with type 2 diabetes. The three peroxisome proliferator-activated receptors (PPARs) PPARalpha, PPAR90 and PPARgamma are essential for the actions of the many insulin sensitizers. PPARalpha activation enhances free fatty acid oxidation and potentiates anti-inflammatory effects, while PPARgamma is essential for normal adipocyte differentiation and proliferation, as well as fatty acid uptake and storage. Thiazolidinediones (TZDs) are selective ligands of PPARgamma and act as insulin sensitizers. TZDs also suppress free fatty acids via the inhibition of lipolysis in adipose tissue. Insulin sensitizers currently under development include partial PPARgamma agonists and antagonists, and dual PPARalpha/PPARgamma agonists. Given that TZDs show anti-inflammatory, anti-oxidant and antiprocoagulant properties in addition to their insulin sensitizing and antilipotoxic properties, a case may be made for initiating TZD therapy early in the treatment of type 2 diabetes, particularly in those patients at risk of cardiovascular disease. TZDs may also be an important therapeutic option in the treatment of metabolic syndrome.

Nonsurgical carotid revascularization.

Carotid endarterectomy is a well-established treatment of improving the carotid luminal diameter and preventing strokes, and the indications and complications are well-defined. Carotid angioplasty and stent placements are relatively newer ways of treating carotid artery stenosis. In certain contexts, they may have some advantages over carotid endarterectomy. However, the success rates, morbidity, and mortality associated with these procedures are less well characterized. In earlier comparative studies, the incidence of ipsilateral stroke rate was higher with angioplasty, but in later studies, this trend is reversing. Angioplasty may also have an edge in specific situations like patients with coexisting significant coronary arterial disease, contralateral carotid artery occlusion, and in instances when the narrowing is long and at multiple sites. Protective devices like distal occlusion balloon and filter protection devices may reduce the incidence of stroke. We are still awaiting the results of some major randomized head-to-head trials comparing carotid endarterectomy and stenting.

Angiotensin receptor blockers in congestive heart failure: evidence, concerns, and controversies.

Heart failure results in neurohormonal activation of which the renin-angiotensin-aldosterone system (RAS) is the main mediator. Activation of this system leads to the production of angiotensin II (ATII), which leads to multiple adverse short-term and long-term effects, including hemodynamic dysfunction, renal dysfunction, inflammation, and cardiac remodeling. Angiotensin-converting enzyme inhibitors (ACEIs) exert favorable effects in congestive heart failure (CHF) by inhibiting the production of ATII. It has been shown that ACEIs may not be able to suppress the production of ATII completely because there are RAS-independent mechanisms of ATII production. Hence, it was thought that angiotensin receptor blockers (ARBs) might be more useful in CHF because they directly block the ATII receptors. Many studies have been done to evaluate the role of ARBs in CHF. We reviewed these studies and have attempted to define the place and ARBs in the therapy for CHF.

Prevalence of stroke and associated risk factors in Asian Indians living in the state of Georgia, United States of America.

This study is the first attempt to assess the prevalence of stroke and associated risk factors in Asian Indians living in the United States. The overall prevalence of stroke is 2.77% (men 3.72% and women 1.77%). Stroke was significantly associated with systemic hypertension, diabetes mellitus, coronary artery disease, end-stage renal disease, and family history of stroke and myocardial infarction.

Prevalence of diabetes mellitus and related conditions in Asian Indians living in the United States.

This study is the first attempt to evaluate the prevalence of diabetes mellitus and related conditions in Asian Indians living in the United States. A community-based survey of 1,046 Asian Indian immigrants living in and around the Atlanta metro area of Georgia was conducted and found an overall prevalence of diabetes mellitus of 18.3% (22.5% in men and 13.6% in women). This prevalence of diabetes mellitus in Asian Indians is much higher than in whites, blacks, and Hispanics living in the United States.

Association of poor glycemic control with prolonged hospital stay in patients with diabetes admitted with exacerbation of congestive heart failure.

OBJECTIVE: To establish a relationship between the control of blood glucose levels and the severity of congestive heart failure (CHF) in a retrospective review of medical records of patients with diabetes admitted with acute exacerbation of CHF and to assess the potential correlation between the number of days of hospitalization and the baseline and in-hospital glycemic status. METHODS: Medical records were reviewed to identify patients with diabetes admitted to a tertiary care center with exacerbation of CHF. Patients in whom any new complications developed that could have prolonged the hospitalization were excluded from the study. The number of days of hospitalization attributable to CHF were noted and statistically correlated with the glycemic control. RESULTS: Data on 100 patients included in the study are presented. The duration of hospitalization ranged from 1 day to 2 weeks (mean, 4.79 +/- 3.03 days). The in-hospital glycemic control strongly correlated positively with the number of days of hospitalization (r = 0.499; 95% confidence interval [CI], 0.325 to 0.643). The admission blood glucose level also showed a strong positive correlation with the days of hospitalization (r = 0.587; 95% CI, 0.426 to 0.720). The mean hemoglobin A1c (HbA1c) correlated positively with the number of days in the hospital (r = 0.653; 95% CI, 0.508 to 0.764). The 51 patients with uncontrolled diabetes (HbA1c >7%) were hospitalized for a mean period of 6.3 +/- 3.2 days, in comparison with a mean duration of 3.2 +/- 1.9 days for the 49 patients with good outpatient glycemic control (HbA1c < or =7%). CONCLUSION: Patients with diabetes admitted with exacerbation of CHF who have poor baseline or in-hospital glycemic control have a prolonged hospitalization.