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A maintained absolute lymphocyte count predicts the overall survival benefit from eribulin therapy, including eribulin re-administration, in HER2-negative advanced breast cancer patients: a single-institutional experience.
Watanabe, J, Saito, M, Horimoto, Y, Nakamoto, S
Breast cancer research and treatment. 2020;(1):211-220
Abstract
PURPOSE Eribulin methylate (eribulin) improved the overall survival (OS) of HER2-negative advanced breast cancer (HER2-ABC) patients; however, the mechanism underlying the OS improvement has not been clarified. Several reports suggest that eribulin promotes antitumor immunity via tumor micro-environment conditioning. Recently, a maintained baseline lymphocyte count was proposed as predictive marker for eribulin therapy in HER2-ABC patients; however, no associations with the OS have been noted. We retrospectively investigated the neutrophil-to-lymphocyte ratio and absolute lymphocyte count (ALC) in HER2-ABC patients receiving eribulin and assessed the utility of eribulin re-administration for further OS improvement. METHODS HER2-ABC patients who received eribulin therapy at Shizuoka Cancer Center between November 2011 and December 2018 were retrospectively analyzed. RESULTS A total of 144 HER2-ABC (108 estrogen receptor-positive [ER+], 36 ER-) patients were identified, and 32 patients (28 ER+ , 4 ER-) were re-administered with eribulin. In the ER+ subgroup, a multivariate analysis showed that an ALC ≥ 1000/μL and re-administration were significantly associated with the OS (hazard ratio [HR] 0.503; P = 0.034 and HR 0.366; P < 0.0001, respectively), and an ALC ≥ 1000/μL was also identified as the only predictive factor for re-administration (HR 0.329; P = 0.033). In contrast, a multivariate analysis in the ER- subgroup identified no predictive markers. CONCLUSION In HER2-ER + ABC patients, ALC was identified as a predictive marker for eribulin therapy, and the re-administration of eribulin is considered a valid therapeutic option for further improvement of the OS.
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Evaluation of the safety and tolerability of a nutritional Formulation in patients with ANgelman Syndrome (FANS): study protocol for a randomized controlled trial.
Herber, DL, Weeber, EJ, D'Agostino, DP, Duis, J
Trials. 2020;(1):60
Abstract
BACKGROUND Ketogenic and low-glycemic-index diets are effective in treating drug-resistant seizures in children with Angelman syndrome. Cognition, mobility, sleep, and gastrointestinal health are intrinsically linked to seizure activity and overall quality of life. Ketogenic and low-glycemic diets restrict carbohydrate consumption and stabilize blood glucose levels. The ketogenic diet induces ketosis, a metabolic state where ketone bodies are preferentially used for fuel. The use of exogenous ketones in promoting ketosis in Angelman syndrome has not been previously studied. The study formulation evaluated herein contains the exogenous ketone beta-hydroxybutyrate to rapidly shift the body towards ketosis, resulting in enhanced metabolic efficiency. METHODS/DESIGN This is a 16-week, randomized, double-blind, placebo-controlled, crossover study to assess the safety and tolerability of a nutritional formula containing exogenous ketones. It also examines the potential for exogenous ketones to improve the patient's nutritional status which can impact the physiologic, symptomatic, and health outcome liabilities of living with Angelman syndrome. DISCUSSION This manuscript outlines the rationale for a study designed to be the first to provide data on nutritional approaches for patients with Angelman syndrome using exogenous ketones. TRIAL REGISTRATION ClinicalTrials.gov, ID: NCT03644693. Registered on 23 August 2018. Last updated on 23 August 2018.
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On the Future Design of Bio-Inspired Polyetheretherketone Dental Implants.
Knaus, J, Schaffarczyk, D, Cölfen, H
Macromolecular bioscience. 2020;(1):e1900239
Abstract
Polyetheretherketone (PEEK) is a promising implant material because of its excellent mechanical characteristics. Although this polymer is a standard material in spinal applications, PEEK is not in use in the manufacturing of dental implants, where titanium is still the most-used material. This may be caused by its relative bio-inertness. By the use of various surface modification techniques, efforts have been made to enhance its osseointegrative characteristics to enable the polymer to be used in dentistry. In this feature paper, the state-of-the-art for dental implants is given and different surface modification techniques of PEEK are discussed. The focus will lie on a covalently attached surface layer mimicking natural bone. The usage of such covalently anchored biomimetic composite materials combines many advantageous properties: A biocompatible organic matrix and a mineral component provide the cells with a surrounding close to natural bone. Bone-related cells may not recognize the implant as a foreign body and therefore, may heal and integrate faster and more firmly. Because neither metal-based nor ceramics are ideal material candidates for a dental implant, the combination of PEEK and a covalently anchored mineralized biopolymer layer may be the start of the desired evolution in dental surgery.
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Insulin resistance and heart failure during treatment with sodium glucose cotransporter 2 inhibitors: proposed role of ketone utilization.
Hattori, Y
Heart failure reviews. 2020;(3):403-408
Abstract
Sodium glucose cotransporter 2 (SGLT2) inhibitors reduce the rate of hospitalization for heart failure in individuals with type 2 diabetes, but the underlying mechanisms remain elusive. Modestly elevated circulating β-hydroxybutyrate (βOHB) during treatment with SGLT2 inhibitors causes different beneficial effects on organs and cells, depending on succinyl-CoA:3-ketoacid CoA transferase (SCOT) levels. In the heart, in which SCOT is highly expressed/up-regulated, βOHB may be an alternative energy source apart from fat and glucose oxidation. The type 2 diabetic failing heart may be energy inefficient. In skeletal muscle, in which SCOT is not highly expressed/down-regulated, βOHB may cause antioxidant effects, resulting in amelioration of insulin resistance, which could lead to improvement in cardiac insulin resistance with metabolic, endocrine, and cytokine alterations. Although various mechanisms have been suggested, we postulate that the potential impact of SGLT2 inhibitors on heart failure lies in fuel energetics and amelioration of insulin resistance with ketone utilization depending upon SCOT levels.
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Incidence of peripheral neuropathy associated with eribulin mesylate versus vinorelbine in patients with metastatic breast cancer: sub-group analysis of a randomized phase III study.
Wu, Y, Wang, Q, Zhang, J, Cao, J, Wang, B, Hu, X
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2020;(8):3819-3829
Abstract
BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most significant neurologic complications of chemotherapy, impacting patient's behavior and quality of life. CIPN is mostly sensory, with rare incidences of autonomic dysfunction and other neuropathy. METHODS We conducted a single-center sub-group analysis of patients with metastatic breast cancer enrolled in a phase III study (NCT02225470) set up to compare eribulin mesylate (1.4 mg/m2 on days 1 and 8 every 21 days) with vinorelbine (25 mg/m2 on days 1, 8, and 15 every 21 days). The analysis investigated incidence of peripheral neuropathy, time to onset of neuropathy, and safety. RESULTS Our analysis included 110 women with a mean age of 50.7 (SD = 10.9). The median accumulated dose of eribulin was 11.2 mg/m2 and 125.0 mg/m2 for vinorelbine. Among patients in the eribulin group, a performance status (ECOG PS) of 2 was correlated with peripheral sensory neuropathy (p = 0.015), and accumulated eribulin dose (≥ 10 mg/m2) was associated with all neuropathy and peripheral sensory neuropathy (p = 0.003 and p = 0.007, respectively). In the vinorelbine group, patient age (≥ 65 years) was positively associated with all neuropathy (p = 0.043). The time to onset of neuropathy appeared to be longer for eribulin versus vinorelbine (35.3 vs. 34.6 weeks; p = 0.046), with a significantly higher incidence of autonomic neuropathy at weeks 2 and 10 observed among patients receiving vinorelbine (p = 0.008 and p = 0.043, respectively). CONCLUSION Vinorelbine is associated with a higher incidence of autonomic neuropathy than eribulin in patients with metastatic breast cancer. Furthermore, the onset of neurotoxicity appears to occur earlier with vinorelbine than eribulin.
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Application of polyetheretherketone cages through minimally invasive oblique retroperitoneal approach for the treatment of lumbar polymicrobial spondylodiscitis: A STROBE-compliant retrospective study with 7 cases.
Luo, W, Zhu, Y, Zhao, ZH, Ou, YS
Medicine. 2020;(17):e18594
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Abstract
Despite the plethora of evidence in support of the use of structural osseous autograft in lumbar spondylodiscitis, attention has recently been turned to the addition of synthetic materials such as polyetheretherketone (PEEK) to restore anterior vertebral column support.From January 2015 to April 2017, 7 patients with lumbar polymicrobial spondylodiscitis were surgically treated with a minimally invasive oblique retroperitoneal approach to the infected focus. The patients underwent a standard lateral minimally invasive oblique retroperitoneal approach using direct lateral interbody fusion system. The PEEK cages were loaded with autologous bone graft. All the patients underwent posterior fixation with percutaneous pedicle screw instrumentation. Lumbar function was measured using Oswestry Disability Index, and pain was measured with visual analog scale. Fusion and subsidence were also recorded.The study included 5 female and 2 male patients. The median age was 58.9 years. The duration of follow-up was 31.8 ± 6.1 months (range: 24-47). All patients recovered from the infection without relapse within 24-month follow-up. Visual analog scale significantly declined from 7.57 ± 0.53 before surgery to 1.57 ± 0.53 at 12-month follow-up. Mean Oswestry Disability Index decreased from 72.14 ± 6.82 before surgery to 22.28 ± 2.13 after surgery. All patients had solid fusion at 2-year follow-up. Fusion occurred at 6 to 15 months (mean 9.8 months).The specific use of PEEK cages in lumbar polymicrobial spondylodiscitis suggests reliable outcome in terms of clinical and imaging outcomes in our limited cases.
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The ketogenic diet and dermatology: a primer on current literature.
Fomin, DA, Handfield, K
Cutis. 2020;(1):40-43
Abstract
The ketogenic diet has been therapeutically employed from antiquity and is still utilized today in many disease states. With the boom of the complementary and alternative health movement over the last 2 decades, the lay population has grown more interested in disease prevention and treatment via dietary and lifestyle changes and enhancing health and human performance. The ketogenic diet, whether exclusive or intermittent, has been purported by health care professionals and laypersons alike to meet these demands. In this review article, we look to the current literature for proven and possible mechanisms by which ketones and a ketogenic diet may be utilized in the field of dermatology and direct our readers to pursue further research for this promising potential treatment option.
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Potential Therapeutic Effects of Exogenous Ketone Supplementation for Type 2 Diabetes: A Review.
Walsh, JJ, Myette-Côté, É, Neudorf, H, Little, JP
Current pharmaceutical design. 2020;(9):958-969
Abstract
Type 2 diabetes (T2D) is among the most prevalent non-communicable lifestyle diseases. We propose that overnutrition and low levels of physical activity can contribute to a vicious cycle of hyperglycemia, inflammation and oxidative stress, insulin resistance, and pancreatic β-cell dysfunction. The pathophysiological manifestations of T2D have a particular impact on the vasculature and individuals with T2D are at high risk of cardiovascular disease. Targeting aspects of the vicious cycle represent therapeutic approaches for improving T2D and protecting against cardiovascular complications. The recent advent of exogenous oral ketone supplements represents a novel, non-pharmacological approach to improving T2D pathophysiology and potentially protecting against cardiovascular disease risk. Herein, we review the emerging literature regarding the effects of exogenous ketone supplementation on metabolic control, inflammation, oxidative stress, and cardiovascular function in humans and highlight the potential application for breaking the vicious cycle of T2D pathophysiology.
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The dark side of the spoon - glucose, ketones and COVID-19: a possible role for ketogenic diet?
Paoli, A, Gorini, S, Caprio, M
Journal of translational medicine. 2020;(1):441
Abstract
The novel coronavirus disease (COVID-19) is posing a serious challenge to the health-care systems worldwide, with an enormous impact on health conditions and loss of lives. Notably, obesity and its related comorbidities are strictly related with worse clinical outcomes of COVID-19 disease. Recently, there is a growing interest in the clinical use of ketogenic diets (KDs), particularly in the context of severe obesity with related metabolic complications. KDs have been proven effective for a rapid reduction of fat mass, preserving lean mass and providing an adequate nutritional status. In particular, the physiological increase in plasma levels of ketone bodies exerts important anti-inflammatory and immunomodulating effects, which may reveal as precious tools to prevent infection and potential adverse outcomes of COVID-19 disease. We discuss here the importance of KDs for a rapid reduction of several critical risk factors for COVID-19, such as obesity, type 2 diabetes and hypertension, based on the known effects of ketone bodies on inflammation, immunity, metabolic profile and cardiovascular function. We do believe that a rapid reduction of all modifiable risk factors, especially obesity with its metabolic complications, should be a pillar of public health policies and interventions, in view of future waves of SARS-CoV-2 infection.
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Acute coffee ingestion with and without medium-chain triglycerides decreases blood oxidative stress markers and increases ketone levels.
McAllister, MJ, Waldman, HS, Rentería, LI, Gonzalez, AE, Butawan, MB, Bloomer, RJ
Canadian journal of physiology and pharmacology. 2020;(4):194-200
Abstract
Ingestion of ketone supplements, caffeine, and medium-chain triglycerides (MCTs) may all be effective strategies to increase blood levels of the ketone body beta-hydroxybutyrate (D-BHB). However, acute ingestion of a bolus of lipids may increase oxidative stress (OS). The purpose of the study was to investigate the impact of adding varying amounts of MCTs to coffee on blood levels of D-BHB and markers of OS. Ten college-aged men ingested coffee with 0, 28, and 42 g of MCT in a randomized order. Blood samples were collected pre- as well as 2 and 4 h postprandial and analyzed for D-BHB, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), glucose, triglycerides (TAG), insulin, and OS markers: advanced oxidation protein products (AOPP), glutathione (GSH), malondialdehyde (MDA), and hydrogen peroxide (H2O2). All three treatments resulted in a significant increase in D-BHB, HDL-c, and TC as well as a significant decrease in TAG, MDA, H2O2, and insulin. The 42 g treatment was associated with significantly higher levels of AOPP and MDA. Acute ingestion of coffee results in favorable changes to markers of cardiometabolic health that were not impacted by the addition of 28 g of MCT. However, 42 g of MCT caused significantly greater OS.