Probiotics and Gut Microbiota in Obesity: Myths and Realities of a New Health Revolution.

Obesity and its comorbidities are humans' most prevalent cardio-metabolic diseases worldwide. Recent evidence has shown that chronic low-grade inflammation is a common feature in all highly prevalent chronic degenerative diseases. In this sense, the gut microbiota is a complete ecosystem involved in different processes like vitamin synthesis, metabolism regulation, and both appetite and immune system control. Thus, dysbiosis has been recognised as one of the many factors associated with obesity due to a predominance of Firmicutes, a decrease in Bifidobacterium in the gut, and a consequent short-chain fatty acids (SCFA) synthesis reduction leading to a reduction in incretins action and intestinal permeability increase. In this context, bacteria, bacterial endotoxins, and toxic bacterial by-products are translocated to the bloodstream, leading to systemic inflammation. This review focuses on gut microbiota composition and its role in obesity, as well as probiotics and prebiotics benefits in obesity.

Specialized Proresolving Lipid Mediators: A Potential Therapeutic Target for Atherosclerosis.

Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty acids, integrated into four families: Lipoxins, Resolvins, Protectins, and Maresins. SPMs have generated interest in recent years due to their ability to promote the resolution of inflammation associated with the pathogeneses of numerous illnesses, particularly CVD. Several preclinical studies in animal models have evidenced their ability to decrease the progression of atherosclerosis, intimal hyperplasia, and reperfusion injury via diverse mechanisms. Large-scale clinical trials are required to determine the effects of SPMs in humans. This review integrates the currently available knowledge of the therapeutic impact of SPMs in CVD from preclinical and clinical studies, along with the implicated molecular pathways. In vitro results have been promising, and as such, SPMs could soon represent a new therapeutic alternative for CVD.

Metabolic Syndrome: Is It Time to Add the Central Nervous System?

Metabolic syndrome (MS) is a set of cardio-metabolic risk factors that includes central obesity, hyperglycemia, hypertension, and dyslipidemias. The syndrome affects 25% of adults worldwide. The definition of MS has evolved over the last 80 years, with various classification systems and criteria, whose limitations and benefits are currently the subject of some controversy. Likewise, hypotheses regarding the etiology of MS add more confusion from clinical and epidemiological points of view. The leading suggestion for the pathophysiology of MS is insulin resistance (IR). IR can affect multiple tissues and organs, from the classic "triumvirate" (myocyte, adipocyte, and hepatocyte) to possible effects on organs considered more recently, such as the central nervous system (CNS). Mild cognitive impairment (MCI) and Alzheimer's disease (AD) may be clinical expressions of CNS involvement. However, the association between MCI and MS is not understood. The bidirectional relationship that seems to exist between these factors raises the questions of which phenomenon occurs first and whether MCI can be a precursor of MS. This review explores shared pathophysiological mechanisms between MCI and MS and establishes a hypothesis of a possible MCI role in the development of IR and the appearance of MS.

Exploring Phytotherapeutic Alternatives for Obesity, Insulin Resistance and Diabetes Mellitus.

At present, the pathologic spectrum of obesity-insulin resistance (IR)-diabetes mellitus (DM) represents not only a pressing matter in public health but also a paramount object of study in biomedical research, as they constitute major risk factors for cardiovascular disease (CVD), and other chronic non-communicable diseases (NCD). Phytotherapy, the use of medicinal herbs (MH) with treatment purposes, offers a wide array of opportunities for innovation in the management of these disorders; mainly as pharmacological research on small molecules accumulates. Several MH has displayed varied mechanisms of action relevant to the pathogenesis of obesity, IR and DM, including immunological and endocrine modulation, reduction of inflammation and oxidative stress (OS), regulation of appetite, thermogenesis and energy homeostasis, sensitisation to insulin function and potentiation of insulin release, among many others. However, the clinical correlates of these molecular phenomena remain relatively uncertain, with only a handful of MH boasting convincing clinical evidence in this regard. This review comprises an exploration of currently available preclinical and clinical research on the role of MH in the management of obesity, IR, and DM.

Phytotherapy for Cardiovascular Disease: A Bench-to-Bedside Approach.

At present, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, and global trends suggest that this panorama will persist or worsen in the near future. Thus, optimization of treatment strategies and the introduction of novel therapeutic alternatives for CVD represent key objectives in contemporary biomedical research. In recent years, phytotherapy-defined as the therapeutic use of whole or minimally modified plant components-has ignited large scientific interest, with a resurgence of abundant investigation on a wide array of medicinal herbs (MH) for CVD and other conditions. Numerous MH have been observed to intervene in the pathophysiology of CVD via a myriad of molecular mechanisms, including antiinflammatory, anti-oxidant, and other beneficial properties, which translate into the amelioration of three essential aspects of the pathogenesis of CVD: Dyslipidemia, atherosclerosis, and hypertension. Although the preclinical data in this scenario is very rich, the true clinical impact of MH and their purported mechanisms of action is less clear, as large-scale robust research in this regard is in relatively early stages and faces important methodological challenges. This review offers a comprehensive look at the most prominent preclinical and clinical evidence currently available concerning the use of MH in the treatment of CVD from a bench-to-bedside approach.

DE-INTENSIFICATION OF DIABETES TREATMENT IN ELDERLY PATIENTS WITH TYPE 2 DIABETES MELLITUS.

Objective: De-intensification of diabetes treatment is recommended in elderly patients with tight glycemic control at high risk of hypoglycemia. However, rates of de-intensification in endocrine practice are unknown. We conducted a retrospective study to evaluate the rate of de-intensification of antidiabetic treatment in elderly patients with type 2 diabetes mellitus (T2DM) and tight glycemic control. Methods: All patients with ≥2 clinic visits over a 1-year period at a major academic diabetes center were included. De-intensification of diabetes treatment was defined as a decrease or discontinuation of any antidiabetic drug without adding another drug, or a reduction in the total daily dose of insulin or a sulfonylurea drug with or without adding a drug without risk of hypoglycemia. Results: Out of 3,186 unique patients, 492 were ≥65 years old with T2DM and hemoglobin A1c (HbA1c) <7.5% (<58 mmol/mol). We found 308 patients treated with a sulfonylurea drug or insulin, 102 of whom had hypoglycemia as per physician note. Among these 102 patients, 38 (37%) were advised to de-intensify therapy. In a subgroup analysis of patients ≥75 years old with HbA1c <7% (<53 mmol/mol), we found that out of 23 patients treated with a sulfonylurea drug or insulin and reporting hypoglycemia, 11 (43%) were advised de-intensification of therapy. There were no significant predictors of de-intensification of treatment. Conclusion: Our study suggests that de-intensification of antidiabetic medications is uncommon in elderly patients with T2DM. Strategies may need to be developed to prevent the potential harm of overtreatment in this population. Abbreviations: ADA = American Diabetes Association; CGM = continuous glucose monitoring; HbA1c = hemoglobin A1c; T2DM = type 2 diabetes mellitus; UKPDS = United Kingdom Prospective Diabetes Study.

Thyroid Abscess: Challenges in Diagnosis and Management.

Thyroid abscess is an uncommon infectious pathology. The thyroid is highly resistant to infection due to high iodine content, capsular encasement, and rich vascularity. Acute suppurative thyroiditis represents <1% of thyroid diseases that could potentially become a life-threatening endocrine emergency. A 48-year-old woman with AIDS presented with 3 days of fever, tender neck swelling, and methicillin-resistant Staphylococcus aureus bacteremia. Apart from leukocytosis, initial laboratory values including thyroid function tests were normal. The initial plain computed tomography scan of the neck and ultrasound scan of the neck were inconclusive as well. By day 4, she worsened, and on repeat computed tomography scan of the neck with contrast, multiloculated abscesses in the thyroid and retro pharynx were seen, which needed emergent drainage. Acute suppurative thyroiditis, a rare disease, occurs in patients with either preexisting disorders of the thyroid or in the immunocompromised. The most common pathogen is Staphylococcus aureus. In our case, we highlight the fact that initial imaging may be negative in the early stages of acute suppurative thyroiditis and lead to an erroneous diagnosis of subacute thyroiditis. There are less than 5 cases of methicillin-resistant Staphylococcus aureus suppurative thyroiditis reported.

Breaking the Barriers in Resident Education: A Quality Improvement Initiative.

INTRODUCTION: In 2013, the American College of Cardiology and American Heart Association updated the cholesterol guideline. Despite strong evidence supporting the recommendations, a discernible gap exists in the number of residents who practice them. Our study aimed to identify barriers hindering residents from guideline implementation. METHODS: Twenty eight residents were administered a preintervention and postintervention questionnaire to identify barriers in guideline application. The questionnaire was categorized into three barriers: knowledge, attitude, and behavior. A multifaceted educational intervention consisting of directed teaching sessions and supervised patient encounters was conducted. RESULTS: Our analysis showed that our residents lacked awareness, familiarity, and self-efficacy in using the cholesterol guideline. The intervention led to significant improvements in awareness (79% vs. 43%, p = .0129), familiarity (61% vs. 29%, p = .0306), and self-efficacy (65% vs. 16%, p = .0018) and achieved a 31% increase in knowledge (p = .0001), 38% in attitude (p = .0001), and 20% in behavior (p = .019). The overall improvement in scores averaged 30% (p = .0001). CONCLUSION: Our quality improvement initiative successfully improved our resident's comprehension and applicability of the 2013 ACC/AHA cholesterol guideline. We recommend a multifaceted educational approach tailored toward addressing specific barriers to improve the practice of evidence-based medicine.

Fatal Pulmonary Embolism in the Setting of Immune Reconstitution Inflammatory Syndrome Attributed to Ovarian Tuberculosis.

In developed countries, tuberculosis remains a health care challenge due to human immunodeficiency virus (HIV) and immigration from endemic regions. The Centers for Disease Control and Prevention reported 9557 new cases in 2015, with extrapulmonary involvement in 20.2% of the cases. We present a 33-year-old woman from Cape Town, South Africa, who developed abdominal pain and fever while working on a cruise ship. She sought medical where she underwent computed tomography of her chest, abdomen, and pelvis with findings suggestive of pulmonary tuberculosis and an 8.9-cm pelvic mass. HIV testing was positive and the patient was started on antiretroviral therapy. Bronchoscopy confirmed the presence of acid-fast bacilli, and she was started on rifampin, isoniazid, pyrazinamide, and ethambutol. She remained persistently febrile, raising suspicion for immune reconstitution inflammatory syndrome. However, despite empiric antibiotics, the patient remained persistently febrile, tachycardic, and on day 10 of admission she went into ventricular fibrillation and expired. Autopsy revealed an occlusive thrombus in the left main pulmonary artery in addition to necrotizing granulomata in multiple organs and bilateral tubo-ovarian abscesses. Postmortem cultures for were positive for Mycobacterium tuberculosis, all consistent with disseminated Mycobacterium tuberculosis. Although previous reports underscore the association between tuberculosis and hypercoagulability, the exact mechanism remains unknown. In this article, we report a case of disseminated tuberculosis complicated by bilateral tubo-ovarian abscesses with fatal pulmonary thrombus formation.

In utero virilization secondary to a maternal Krukenberg tumor: case report and review of literature.

BACKGROUND: Krukenberg tumors are ovarian metastatic adenocarcinomas with a primary origin usually located in the stomach, colon, gallbladder, pancreas, or breast. Occasionally, these tumors produce virilization in the affected individual due to androgen production by luteinization of the tumoral stroma. It is believed that during pregnancy these tumors are more likely to increase androgen production due to the elevated levels of human chorionic gonadotropin (hCG). High maternal androgens can cross the placenta producing virilization of the female fetus. CASE PRESENTATION: A 46,XX newborn female, whose mother was diagnosed with a metastatic ovarian tumor during her second trimester of gestation associated with worsening hirsutism and acne, was found to have ambiguous genitalia at birth. Testosterone levels in both the mother and infant were elevated. Follow-up laboratory tests showed progressive normalization of circulating androgens after delivery. CONCLUSIONS: Krukenberg tumors are rare and may produce virilization of the mother and the female fetus when present during pregnancy.

Left Atrial Size and Heart Failure Hospitalization in Patients with Diastolic Dysfunction and Preserved Ejection Fraction.

CONTEXT: Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome associated with diastolic function abnormalities. It remains unclear which factors, if any, can predict the transition from asymptomatic diastolic dysfunction to an overt symptomatic phase. MATERIALS AND METHODS: Patients hospitalized with suspected heart failure between January 2012 and November 2014 with a transthoracic echocardiogram demonstrating preserved systolic function were screened (n = 425). Patients meeting the American College of Cardiology Foundation/American Heart Association definition for HFpEF (n = 40) were matched in a 1:1 fashion to individuals admitted for hypertensive urgency with diastolic dysfunction and neither pulmonary edema nor history of heart failure (n = 40). The clinical records and echocardiograms of all eighty patients included in this retrospective study were reviewed. RESULTS: Patients with HFpEF had higher body mass index (BMI), creatinine, beta-blocker use, and Grade 2 diastolic dysfunction when compared to the hypertensive control population. Echocardiographic analysis demonstrated higher right ventricular systolic pressures, left ventricular mass index, E/A, and E/e' in patients with HFpEF. Similarly, differences were observed in most left atrial (LA) parameters including larger LA maximum and minimum volume indices, as well as smaller LA-emptying fractions in the heart failure group. Multivariate logistic regression analysis revealed LA minimum volume index (odds ratio [OR]: 1.23 [1.09-1.38], P = 0.001) to have the strongest association with heart failure hospitalization after adjustment for creatinine (OR: 7.09 [1.43-35.07], P = 0.016) and BMI (OR: 1.11 [0.99-1.25], P = 0.074). CONCLUSION: LA minimum volume index best correlated with HFpEF in this patient cohort with diastolic dysfunction.

Intrathyroidal Clear Cell Tumor of Parathyroid Origin with Review of Literature.

Water-clear cell adenoma (WCCA) of the parathyroid gland is an exceedingly rare neoplasm. To date, 17 cases have been reported in the literature, with only one of them being intrathyroidal. Here we report a case of a 34-year-old woman who presented for evaluation of a goiter and was found to have a thyroid nodule and abnormal thyroid function tests (TFT). Fine needle aspiration biopsy of the nodule revealed thyroid follicular cells without atypia and subsequent Afirma® Gene Expression Classifier (GEC) testing results were suspicious for malignancy. As a result, the patient underwent a right thyroid lobectomy and isthmusectomy. Histological sections revealed an intrathyroidal nodule consistent with a clear cell neoplasm of parathyroid origin. The histologic appearance together with the immune profile was diagnostic of WCCA, with diffuse positivity for GATA3, focal weak positivity for parathyroid hormone, and negativity for PAX8, thyroglobulin, TTF1, synaptophysin, chromogranin, and S100p. Our study focuses on the clinical presentation, current management strategies, and review of the available literature surrounding this rare diagnosis. The ultimate goal is to help endocrinologists and surgeons establish a foundational treatment plan for intrathyroidal clear cell tumor cases.

An Occult Malignancy Behind a Demyelinating Disease: POEMS Syndrome.

We report a case of a 38-year-old man presenting with bilateral lower extremity weakness and paresthesias that progressed during a 4-month period to severe polyneuropathy forcing the patient to be bed bound. Throughout his multiple hospitalizations, he was treated erroneously for chronic inflammatory demyelinating polyneuropathy, without significant improvement in his symptoms. In addition, he developed hepatosplenomegaly (organomegaly); endocrinopathies such as diabetes mellitus, central hypogonadism, and hypothyroidism; monoclonal spike evidenced in the serum electrophoresis; and hyperpigmentation of skin, altogether consistent with POEMS syndrome. During his last hospitalization he developed excruciating pain on his left hip, and imaging revealed the presence of a 9 × 6 cm osteolytic mass with sclerotic rim in the left acetabulum. Biopsy of the mass confirmed an isolated IgG lambda plasmacytoma. The patient received radiation to his left acetabular lesion followed by left hip replacement. Subsequently, the patient underwent autologous bone marrow transplant. Eighteen months after his initial presentation, he had satisfactory clinical response and is functional without significant limitations. POEMS syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell disorder, which can oftentimes be overlooked and misdiagnosed. The median age of presentation is 51 years, and only 31% of the cases occur in fairly young patients under the age of 45 as evidenced in this case. As clinicians, we should be aware of the constellation of features associated with POEMS syndrome and be able to recognize them promptly.