The emerging role of oxylipins in thrombosis and diabetes.

The prevalence of cardiovascular disease (CVD), the leading cause of death in the US, is predicted to increase due to the shift in age of the general population and increase in CVD risk factors such as obesity and diabetes. New therapies are required to decrease the prevalence of CVD risk factors (obesity and diabetes) as well as reduce atherothrombosis, the major cause of CVD related mortality. Oxylipins, bioactive metabolites derived from the oxygenation of polyunsaturated fatty acids, play a role in the progression of CVD risk factors and thrombosis. Aspirin, a cyclooxygenase-1 inhibitor, decreases atherothrombotic associated mortality by 25%. These potent effects of aspirin have shown the utility of modulating oxylipin signaling pathways to decrease CVD mortality. The role of many oxylipins in the progression of CVD, however, is still uncertain or controversial. An increased understanding of the role oxylipins play in CVD risk factors and thrombosis could lead to new therapies to decrease the prevalence of CVD and its associated mortality

Week 26 results from the PaTH Forward Open-Label Extension Trial Support TransCon PTH as a potential hormone replacement therapy for patients with hypoparathyroidism

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Open-Label Extension of a Randomized Trial Investigating Safety and Efficacy of rhPTH(1-84) in Hypoparathyroidism

Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for treating HypoPT. The present study (NCT03364738) was a phase 4, 1-yr open-label extension of PARALLAX. Patients received only 2 doses of rhPTH(1-84) in PARALLAX and were considered treatment-naive at the start of the current study. rhPTH(1-84) was initiated at 50 μg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and healthcare resource utilization (HCRU) were assessed. The mean age of the 22 patients included was 50.0 yr; 81.8% were women, and 90.9% were White. By the end of treatment (EOT), 95.5% of patients had albumin-corrected serum calcium values in the protocol-defined range of 1.88 mmol/L to the upper limit of normal. Serum phosphorus was within the healthy range, and albumin-corrected serum calcium-phosphorus product was below the upper healthy limit throughout, while mean 24-h urine calcium excretion decreased from baseline to EOT. Mean supplemental doses of calcium and active vitamin D were reduced from baseline to EOT (2402-855 mg/d and 0.8-0.2 μg/d, respectively). Mean serum bone turnover markers, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and type I collagen C-telopeptide increased 2-5 fold from baseline to EOT. The HCRU, disease-related symptoms and impact on HRQoL improved numerically between baseline and EOT. Nine patients (40.9%) experienced treatment-related adverse events; no deaths were reported. Treatment with rhPTH(1-84) once daily for 1 yr improved HRQoL, maintained eucalcemia in 95% of patients, normalized serum phosphorus, and decreased urine calcium excretion. The effects observed on urine calcium and the safety profile are consistent with previous findings. CLINICAL TRIAL IDENTIFIER: NCT03364738

A clinical study of arrhythmias associated with acute coronary syndrome: a hospital based study of a high risk and previously undocumented population

Background: ACS represents a global epidemic. Arrhythmia in ACS is common. Careful investigation may lead to further improvement of prognosis. Retrospectively analyzed the year- round data of our center. Study was undertaken to analyze the incidence, frequency and type of arrhythmias in ACS. This is to aid timely intervention and to modify the outcome. Identification of the type of arrhythmia is of therapeutic and prognostic importance.Methods: This cross sectional analytical study was conducted in the Department of Cardiology, Apollo Hospitals Dhaka, from January 2019 to January 2020 with ACS patients. Enrolled consecutively and data analyzed.Results: There were 500 patients enrolled considering inclusion and exclusion criteria. Sample was subdivided into 3 groups on the type of ACS. Group-I with UA, Group-II with NSTE - ACS and Group-III with STE - ACS. Different types of arrhythmia noted. Types of arrhythmia were correlated with type of ACS. 500 patients included. Mean age 55.53±12.70, 71.6% male and 28.4% female. 60.4% hypertensive, 46.2% diabetic, 20.2% positive family history of CAD, 32.2% current smoker, 56.4% dyslipidaemic and 9.6% asthmatic. 31.2% UA, 39.2% NSTE-ACS and 29.6% STE-ACS. Type of arrhythmias noted. 22% sinus tachycardia, 20.2% sinus bradycardia, 9% atrial fibrillation, 5.2% ventricular ectopic, 4.8% supra ventricular ectopic, 2.8% bundle branch block, 2.2% atrio-ventricular block, 1% broad complex tachycardia, 0.4% narrow complex tachycardia, 0.2% sinus node dysfunction and 32.2% without any arrhythmia. Significant incidences of arrhythmia detected - respectively 29.8%, 39.2% and 31%, p<0.001.Conclusions: In conclusion, arrhythmias in ACS are common. More attention should be paid to improve their treatment and prognosis

A Case of Diabetic Muscle Infarction Despite Good Diabetic Control

Case Presentation A 52 year-old female with type 2 diabetes of 10-year durationwas admitted with worsening of shooting pain and swellingof her lower extremities over the previous nine days. Thepain was rated 10/10 in severity, was worse in the right side ascompared to the left, radiated from her lower legs to thighs, andlimited her mobility for the previous five days. She reportedno history of trauma, fever, chills, skin changes, or medicationnoncompliance. She was managing her diabetes with twoinjections of premixed insulin. Her other medical problemsinclude a history of congestive heart failure with an ejectionfraction of 45%, coronary artery disease, stage 4 chronic kidneydisease, and hypertension. A review of systems was remarkablefor exertional dyspnea and mild ascites

Step Stress Partially Accelerated Life Tests and Estimating Costs of Maintenance Service Policy for the Power Function Distribution under Progressive Type-II Censoring

The present paper illustrates how to analyze and design the accelerated life testing (ALTg) plans for the improvement of the quality and reliability of the product. We focus on estimating the costs of maintenance service policy because it plays a very important role in manufacturing organization and providing cost-effective equipment and maintenance.. When the lifetime of units follows power function distribution, the partially step-stress accelerated life test is assumed. The maximum likelihood estimates (MLEs) are obtained under the progressive Type-II censoring. Using the Fisher Information matrix, the asymptotic variance and covariance matrix are obtained. The confidence intervals (CIs) of the estimators are also constructed. Furthermor, a simulation study is conducted to check the results accuracy

Accelerated Life Test Plans and Age-Replacement Policy under Warranty on Burr Type-X distribution with Type-II Censoring

In this paper, we describe how to design and analyze the accelerated life testing (ALTg) plans for the improvement of the quality and the reliability of the product. We also focus on finding the expected cost rate and the expected total cost for age-replacement under warranty policy. The problem is studied using constant stress, under the assumption that the lifetimes of the units follow Burr Type-X distribution for predicting the cost of age replacement under warranty policy. Asymptotic variance and covariance matrix of the estimators are obtained by using the Fisher Information Matrix. Confidence intervals for parameters and respective errors are also obtained. A simulation study is performed to illustrate the statistical properties of the parameters and confidence bound. In the last, numerical examples are also carried out to illustrate the theoretical results

Recent advances in the management of hyponatremia in cancer patients

Hyponatremia is the most frequently encountered electrolyte disorder in cancer patients and is usually multifactorial in its origin. In this review, we discuss the predisposing factors, pathophysiology, clinical symptomatology, and currently available diagnostic and therapeutic options for the management of hyponatremia. In addition to paraneoplastic syndromes, concurrent chemotherapy and comorbidities predispose oncology patients to the risk of hyponatremia. Initial symptoms and signs can be subtle and the prompt evaluation and initiation of treatment is of paramount importance to prevent neurocognitive and other complications. The syndrome of inappropriate antidiuresis (SIAD) is the most common cause of hyponatremia, and the use of serum and urine parameters that distinguish SIAD from other etiologies is discussed. Individualized treatment is preferred depending on the underlying cause and severity of hyponatremia. The treatment of hyponatremia is reviewed and the importance of avoiding rapid overcorrection of the sodium level to reduce the risk of osmotic demyelination syndrome is emphasized. Vasopressin receptor antagonists (vaptans) offer a direct approach to the management of euvolemic and hypervolemic hyponatremia, but the indications for their use and long-term safety need to be clarified. The treatment of hyponatremia is likely to reduce complications and improve survival in cancer patients

Potassium hydroxide (KOH) wet preparation for the laboratory diagnosis of suppurative corneal ulcer

Background: Suppurative keratitis is a common ophthalmic condition mostly caused by fungi. Apart from fungal culture, wet preparation using 10% Potassium hydroxide (KOH) for microscopic detection of fungal elements is a rapid and accurate method of laboratory diagnosis. Purpose: This prospective and cross sectional study was undertaken in order to evaluate the diagnostic sensitivity of wet preparation microscopy using KOH for detection of fungal agents from suppurative corneal ulcer patients. Methodology: Fifty six (56) consecutive clinically suspected patients of suppurative corneal ulcer attending Rajshahi Medical College Hospital (RMCH) during the period from July, 06 to June, 07 were included. Corneal swabs were taken aseptically for detection of bacteria in gram-stained smear and culture. Conventional mechanical corneal scrapings were collected under topical anesthesia and utilized for microscopic detection of fungal agents in KOH wet preparation and fungal cultures in the department of Microbiology of Rajshahi Medical College. Results: Culture yielded microbial growths in 47(83.93%) out of 56 samples of corneal ulcer that included 24 (42.86%) pure fungal growths, 14 (25.0%) pure bacterial growths and 09 (16.07%) mixed microbial growths (both bacteria and fungi). Direct microscopical examination using 10% KOH wet preparation detected 28 fungal agents out of total 33 fungal cases (combining both pure and mixed fungal growths in culture). Diagnostic sensitivity of wet preparation microscopy was found to be 84.85% by comparing its performance to fungal culture yields, which is the ‘gold standard’ for laboratory diagnosis. Conclusion: This limited study has revealed that wet preparation can be a tentative diagnosis of fungal keratitis and can be accurately relied upon for initiating prompt anti-fungal therapy and also recommended as a cost-effective method for laboratory diagnosis especially where culture facility is not available