Fish Oil Derivatives in Hypertriglyceridemia: Mechanism and Cardiovascular Prevention: What Do Studies Say?

Hypertriglyceridemia is a type of dyslipidemia characterized by high triglyceride levels in the blood and increases the risk of cardiovascular disease. Conventional management includes antilipidemic medications such as statins, lowering LDL and triglyceride levels as well as raising HDL levels. However, the treatment may be stratified using omega-3 fatty acid supplements such as eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA), aka fish oil derivatives. Studies have shown that fish oil supplements reduce the risk of cardiovascular diseases; however, the underlying mechanism and the extent of reduction in CVD need more clarification. Our paper aims to review the clinical trials and observational studies in the current literature, investigating the use of fish oil and its benefits on the cardiovascular system as well as the proposed underlying mechanism.

Predictive Value of Voiding Efficiency After Active Void Trial in Men Undergoing BPH Surgery.

OBJECTIVES: To determine the predictive value of voiding efficiency on acute urinary retention after discharge from BPH surgery. MATERIALS AND METHODS: We performed a prospective observational cohort study of three surgeons' practices from 2019 to present. All men included underwent trial of void on post-operative day one after transurethral resection of prostate or Holmium enucleation of prostate . Active filling void trials were performed on all patients and voiding efficiency (percent of bladder volume emptied) was calculated. Multivariable logistic regression was performed to determine predictors of developing acute urinary retention. RESULTS: During the study period, 188 men met inclusion criteria. 110 (59%) men underwent Holmium enucleation of prostate , and 78 (41%) underwent transurethral resection of prostate. The median age of our cohort was 70 (IQR 65-75). The median prostate size was 100g (IQR 61-138g). Nineteen patients (10%) returned after discharge with acute urinary retention requiring catheterization. On post-operative day one, the median voiding efficiency was 75% (IQR 55%-94%). On multivariable analysis, patients with a voiding efficiency less than 50% were 3.8 times more likely (95% confidence interval 1.1-12.8) to develop subsequent retention compared to a voiding efficiency of greater than 75%. Increasing pre-operative prostate size was associated with lower risk of urinary retention after discharge (aOR 0.8, 95%CI 0.6-0.9). CONCLUSIONS: Voiding efficiency after an active void trial helps stratify risk of urinary retention in patients undergoing benign prostate surgery. High-risk patients include those with voiding efficiencies less than 50% and smaller pre-operative prostate sizes (<80g).

Thiamine Supplementation in Patients With Alcohol Use Disorder Presenting With Acute Critical Illness : A Nationwide Retrospective Observational Study.

BACKGROUND: Thiamine supplementation is recommended for patients with alcohol use disorder (AUD). The authors hypothesize that critically ill patients with AUD are commonly not given thiamine supplementation. OBJECTIVE: To describe thiamine supplementation incidence in patients with AUD and various critical illnesses (alcohol withdrawal, septic shock, traumatic brain injury [TBI], and diabetic ketoacidosis [DKA]) in the United States. DESIGN: Retrospective observational study. SETTING: Cerner Health Facts database. PATIENTS: Adult patients with a diagnosis of AUD who were admitted to the intensive care unit with alcohol withdrawal, septic shock, TBI, or DKA between 2010 and 2017. MEASUREMENTS: Incidence and predicted probability of thiamine supplementation in alcohol withdrawal and other critical illnesses. RESULTS: The study included 14 998 patients with AUD. Mean age was 52.2 years, 77% of participants were male, and in-hospital mortality was 9%. Overall, 7689 patients (51%) received thiamine supplementation. The incidence of thiamine supplementation was 59% for alcohol withdrawal, 26% for septic shock, 41% for TBI, and 24% for DKA. Most of those receiving thiamine (n = 3957 [52%]) received it within 12 hours of presentation in the emergency department. The predominant route of thiamine administration was enteral (n = 3119 [41%]). LIMITATION: Specific dosing and duration were not completely captured. CONCLUSION: Thiamine supplementation was not provided to almost half of all patients with AUD, raising a quality-of-care issue for this cohort. Supplementation was numerically less frequent in patients with septic shock, DKA, or TBI than in those with alcohol withdrawal. These data will be important for the design of quality improvement studies in critically ill patients with AUD. PRIMARY FUNDING SOURCE: National Institutes of Health.

A Comprehensive Review of Alternative Therapies for the Management of Chronic Pain Patients: Acupuncture, Tai Chi, Osteopathic Manipulative Medicine, and Chiropractic Care.

INTRODUCTION: Non-pharmacologic alternative therapies for pain have been around for a long time, some for hundreds of years. They have been used throughout history to treat many issues. RECENT FINDINGS: Currently, alternative medicine is most frequently used to treat musculoskeletal pain, and between 59 and 90% of patients utilizing alternative therapies for chronic pain claimed they were helpful and can serve as an effective adjunctive for the treatment of chronic pain. Some examples of alternative therapies that will be discussed in this review include acupuncture, tai chi, osteopathic manipulation, and chiropractic care. Acupuncture, traditionally a Chinese practice, is becoming more popular across the world to attempt to relieve pain. It involves the placement of thin needles at various points in the body. The efficacy of acupuncture for pain is heavily debated. More research and discussion are necessary to determine the exact role it plays in the treatment of chronic pain. Tai chi is also a traditional Chinese practice that is often used as a form of meditation and for potential health benefits. Tai chi involves a series of complex movements such as squatting combined with deep breathing to achieve relaxation and pain reduction. Osteopathic manipulative treatment (OMT) is a technique used by both osteopathic physicians (DO) as well as other health professionals to manage a wide range of conditions in any given patient. The technique involves utilization and manipulation of the musculoskeletal system to achieve potential health benefits. OMT has been used as therapy for many issues but is commonly used for pain conditions. Alternative therapies may serve as an effective adjunctive treatment modality for the management of chronic pain conditions. There has been a tremendous amount of research dictating the effectiveness of alternative therapies for chronic pain management. The purpose of this review is to provide a comprehensive evidence-based update of alternative therapy used for the management of chronic pain conditions.

Pharmacological options for the treatment of chronic migraine pain.

Migraine is a debilitating neurological condition with symptoms typically consisting of unilateral and pulsating headache, sensitivity to sensory stimuli, nausea, and vomiting. The World Health Organization (WHO) reports that migraine is the third most prevalent medical disorder and second most disabling neurological condition in the world. There are several options for preventive migraine treatments that include, but are not limited to, anticonvulsants, antidepressants, beta blockers, calcium channel blockers, botulinum toxins, NSAIDs, riboflavin, and magnesium. Patients may also benefit from adjunct nonpharmacological options in the comprehensive prevention of migraines, such as cognitive behavior therapy, relaxation therapies, biofeedback, lifestyle guidance, and education. Preventative therapies are an essential component of the overall approach to the pharmacological treatment of migraine. Comparative studies of newer therapies are needed to help patients receive the best treatment option for chronic migraine pain.

Assessment of bleeding incidences associated with rivaroxaban therapy in adults with solid tumors.

PURPOSE: Report bleeding incidences associated with rivaroxaban in adult patients with solid tumor malignancies requiring anticoagulation therapy. METHODS: This retrospective review was conducted at Indiana University Health, University Hospital and the Simon Cancer Center in Indianapolis, IN from January 2013 - February 2016. Patients were included if they had a solid tumor malignancy and prescribed rivaroxaban. Data were collected on 144 patients. Major bleeding was defined as bleeding requiring treatment (local, systemic treatment, blood cell transfusions) or hospitalization and minor bleeding was defined as bleeding not requiring treatment or hospitalization. RESULTS: Sixty-four (44%) patients experienced bleeding while on rivaroxaban. There were six cancer types that had a higher incidence of bleeding: bladder, breast, melanoma, pancreas, prostate, and renal cell cancers; 40% (6/15) of patients with bladder cancer experienced bleeding; 54% (7/13) with breast cancer experienced bleeding; 40% (4/10) of patients with melanoma experienced bleeding; 58% (11/19) of patients with pancreatic cancer experienced bleeding; 45% (10/22) of patients with prostate cancer experienced bleeding; and 56% (5/9) of patients with renal cell carcinoma experienced bleeding. No other data collected identified increased incidence of bleeding. CONCLUSIONS: Patients on rivaroxaban with a diagnosis of bladder, breast, melanoma, pancreas, prostate, or renal cell cancers had a higher incidence of bleeding compared to other solid tumors. Major bleeding was higher in bladder, breast, pancreas, and renal cell carcinomas, while minor bleeding was higher in patients with melanoma and prostate cancer.

BDNF: An Oncogene or Tumor Suppressor?

Neurotrophins are a family of growth factors that are vital to the proper development of the central nervous system. Their effects on cells are governed by the expression and activation of the tyrosine kinase receptors TrkA, TrkB and TrkC. TrkB has been immensely implicated in mediating neuronal migration, development and differentiation. It has also been shown to protect several neuronal cell types from an array of cytotoxic stressors after activation by its conjugate ligand brain-derived neurotrophic factor (BDNF). Over the past two decades, it has been shown that TrkB and BDNF are up-regulated in many types of cancers, conferring aggressive phenotypes underpinned by their resistance to several standard chemotherapeutic agents. This resistance to chemotherapy is modulated by the downstream targets of the TrkB receptor which include the well-characterized PI3K /Akt growth pathway, a hallmark of uncontrolled cancer cell growth and proliferation. Pre-clinical efforts to develop inhibitors of this receptor are promising, and such inhibitors also seem to sensitize cancer cells to standard chemotherapies. However, new evidence suggests that BDNF overexpression in the hypothalamus has immunoaugmenting properties, eliciting an increased anti-tumor immune response and reducing the activity of several proteins that would normally confer resistance to chemotherapeutic agents. In the current work, we provide a global analysis of the physiological consequences of TrkB receptor activation in vitro and discuss the dynamic consequences of TrkB activation in vivo. Finally, we propose a clinically-feasible option for increasing BDNF expression in the hypothalamus to more readily utilize the oncolytic effects of BDNF.

Thiamine as a Renal Protective Agent in Septic Shock. A Secondary Analysis of a Randomized, Double-Blind, Placebo-controlled Trial.

RATIONALE: Acute kidney injury (AKI) is common in patients with sepsis and has been associated with high mortality rates. The provision of thiamine to patients with sepsis may reduce the incidence and severity of sepsis-related AKI and thereby prevent renal failure requiring renal replacement therapy (RRT). OBJECTIVES: To test the hypothesis that thiamine supplementation mitigates kidney injury in septic shock. METHODS: This was a secondary analysis of a single-center, randomized, double-blind trial comparing thiamine to placebo in patients with septic shock. Renal function, need for RRT, timing of hemodialysis catheter placement, and timing of RRT initiation were abstracted. The baseline creatinine and worst creatinine values between 3 and 24 hours, 24 and 48 hours, and 48 and 72 hours were likewise abstracted. RESULTS: There were 70 patients eligible for analysis after excluding 10 patients in whom hemodialysis was initiated before study drug administration. Baseline serum creatinine in the thiamine group was 1.2 mg/dl (interquartile range, 0.8-2.5) as compared with 1.8 mg/dl (interquartile range, 1.3-2.7) in the placebo group (P = 0.3). After initiation of the study drug, more patients in the placebo group than in the thiamine group were started on RRT (eight [21%] vs. one [3%]; P = 0.04). In the repeated measures analysis adjusting for the baseline creatinine level, the worst creatinine levels were higher in the placebo group than in the thiamine group (P = 0.05). CONCLUSIONS: In this post hoc analysis of a randomized controlled trial, patients with septic shock randomized to receive thiamine had lower serum creatinine levels and a lower rate of progression to RRT than patients randomized to placebo. These findings should be considered hypothesis generating and can be used as a foundation for further, prospective investigation in this area.

Positron Emission Tomography/Computed Tomography for Gynecologic Malignancies.

IMPORTANCE: Positron emission tomography/Computed tomography(PET/CT) is widely used for gynecologic cancers. OBJECTIVE: To determine when PET/CT should be used for gynecologic cancers. EVIDENCE ACQUISITION: PubMed was reviewed for articles on PET/CT of all gynecologic cancers. National Comprehensive Cancer Network, Society of Gynecologic Oncology, and American College of Radiology guidelines were reviewed. RESULTS: Whole-body PET/CT is useful for (1) initial staging of cervical and endometrial cancer, posttherapy assessment, radiation therapy planning, and posttreatment surveillance of cervical cancer, and (2) assessment of recurrence of cervical, endometrial, or ovarian cancer in the presence of symptoms. It is also useful for staging and recurrence of uterine sarcomas, and for staging of vulvar and vaginal cancer. CONCLUSIONS: Positron emission tomography/Computed tomography is clinically valuable for a variety of gynecologic cancers. RELEVANCE: PET/CT plays an important role in detection of initial disease and recurrence of gynecologic malignancies.

Omega-3 PUFA supplementation and the response to evoked endotoxemia in healthy volunteers.

SCOPE: Fish oil-derived n-3 PUFA may improve cardiometabolic health through modulation of innate immunity. However, findings in clinical studies are conflicting. We hypothesized that n-3 PUFA supplementation would dose-dependently reduce the systemic inflammatory response to experimental endotoxemia in healthy humans. METHODS AND RESULTS: The Fenofibrate and omega-3 Fatty Acid Modulation of Endotoxemia (FFAME) study was an 8-wk randomized double-blind trial of placebo or n-3 PUFA supplementation (Lovaza 465 mg eicosapentaenoic acid (EPA) + 375 mg docosahexaenoic acid (DHA)) at "low" (1/day, 900 mg) or "high" (4/day, 3600 mg) dose in healthy individuals (N = 60; age 18-45; BMI 18-30; 43% female; 65% European-, 20% African-, 15% Asian-ancestry) before a low-dose endotoxin challenge (LPS 0.6 ng/kg intravenous bolus). The endotoxemia-induced temperature increase was significantly reduced with high-dose (p = 0.03) but not low-dose EPA + DHA compared to placebo. Although there was no statistically significant impact of EPA + DHA on individual inflammatory responses (tumor necrosis factor-α (TNF-α), IL-6, monocyte chemotactic protein (MCP-1), IL-1 receptor agonist (IL-1RA), IL-10, C-reactive protein (CRP), serum amyloid A (SAA)), there was a pattern of lower responses across all biomarkers with high-dose (nine of nine observed), but not low-dose EPA + DHA. CONCLUSION: EPA + DHA at 3600 mg/day, but not 900 mg/day, reduced fever and had a pattern of attenuated LPS induction of plasma inflammatory markers during endotoxemia. Clinically and nutritionally relevant long-chain n-3 PUFA regimens may have specific, dose-dependent, anti-inflammatory actions.