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Cardiovascular Diagnosis and Therapy Feb 2020Hypertrophic cardiomyopathy is a genetically determined disorder resulting in left ventricular hypertrophy. In a majority of the estimated 20 million people affected... (Review)
Review
Hypertrophic cardiomyopathy is a genetically determined disorder resulting in left ventricular hypertrophy. In a majority of the estimated 20 million people affected worldwide, left ventricular outflow obstruction is present at rest or with provocation. The presence and degree of obstruction influence the symptomatic presentation, treatment strategies and prognosis of affected individuals. Pharmacologic therapy with beta-adrenergic blocking drugs and calcium channel blockers is the principal treatment strategy in symptomatic patients with left ventricular outflow obstruction but is ineffective in many patients. When symptoms of exertional shortness of breath, chest pain and/or syncope prove refractory to medical therapy and there is persisting left ventricular outflow obstruction, or when there is drug intolerance, septal reduction strategies (surgical myectomy and alcohol septal ablation) are quite effective. Selection of the optimal septal reduction strategy for a given patient has become controversial and is determined largely by the medical system providing treatment strategies for the patient. Regretably, there are no randomized trials comparing myectomy and ablation and none are anticipated. The comprehensive Hypertrophic Cardiomyopathy Guideline Statements published in 2011 and 2014 differ significantly with the earlier statement favoring surgical myectomy and the more recent statement giving equal class I status to the two septal reduction strategies in adult patients with drug-refractory symptoms. Recently published studies of long-term follow-up of patients after alcohol septal ablation in Europe, where surgical myectomy is rarely performed, confirm long-term safety and effectiveness with survival free of cardiac events exceeding 96% at 15 years. The lesser degree of discomfort and more rapid recovery associated with the minimally invasive catheter-based alcohol ablation procedure coupled with the recently published long-term safety data favor an increased use of this strategy in symptomatic adult patients with hypertrophic obstructive cardiomyopathy (HOCM).
PubMed: 32175226
DOI: 10.21037/cdt.2019.07.02 -
Journal of Health Psychology Jul 2023The COVID-19 pandemic continues to impact global psychological wellbeing. To investigate the sustained impact of COVID-19 on wellbeing, the current study longitudinally...
The COVID-19 pandemic continues to impact global psychological wellbeing. To investigate the sustained impact of COVID-19 on wellbeing, the current study longitudinally assessed fear of COVID-19, anxiety, depression, intolerance of uncertainty, worry, sleep quality, loneliness and alcohol use during the pandemic in the United Kingdom. Timepoint 1 (T1; = 445) took place in February 2021 following the highest number of pandemic-related deaths in the UK. Timepoint 2 (T2, = 198) took place in June 2021 when pandemic-related deaths had declined considerably, and many had been vaccinated. At T1, COVID-19 fear predicted elevated levels of anxiety, depression, intolerance of uncertainty, worry, sleep quality and loneliness. At T2, we observed that levels of COVID-19 fear, depression, loneliness and sleep quality decreased. However, COVID-19 fear continued to predict elevated intolerance of uncertainty, worry and impaired sleep quality. These findings demonstrate the longitudinal impact of COVID-19 fear on psychological wellbeing.
Topics: Humans; Pandemics; COVID-19; Fear; Anxiety; United Kingdom; Depression
PubMed: 36397647
DOI: 10.1177/13591053221134848 -
Journal of Personality Disorders Jun 2021Despite increasing recognition that intolerance of uncertainty is a transdiagnostic dimension of psychopathology, very little research has investigated its relevance for...
Despite increasing recognition that intolerance of uncertainty is a transdiagnostic dimension of psychopathology, very little research has investigated its relevance for externalizing psychopathology and related risky/impulsive behavior. Ninety-five unselected adults (ages 19-55, 53% men) recruited from the community completed a measure of intolerance of uncertainty, externalizing traits and problems, and risky/impulsive behavior. Higher levels of intolerance of uncertainty were associated with greater endorsement of externalizing symptoms (e.g., aggression, alcohol/marijuana use, problematic impulsivity) and last-month risky and impulsive behaviors. Relations between intolerance of uncertainty and externalizing symptoms/risky behaviors were mediated by a motivation to engage in these behaviors to avoid distress, but not by the motivation to experience pleasurable emotions. Findings suggest that difficulty tolerating uncertainty may confer risk for the externalizing spectrum of psychopathology by increasing the likelihood that an individual will engage in risky behaviors to alleviate distressing or unpleasant emotions.
Topics: Adult; Female; Humans; Impulsive Behavior; Male; Middle Aged; Psychopathology; Risk-Taking; Substance-Related Disorders; Uncertainty; Young Adult
PubMed: 31682196
DOI: 10.1521/pedi_2019_33_456 -
PloS One 2022Non-alcoholic fatty liver disease (NAFLD) ranks first among liver diseases in Western countries. NAFLD is typically associated with obesity and diabetes, however it also...
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) ranks first among liver diseases in Western countries. NAFLD is typically associated with obesity and diabetes, however it also develops in lean individuals without metabolic syndrome. The prevalence of lean NAFLD is 7 percent in the U.S. and 25-30 percent in some Asian countries. NAFLD starts with excess liver fat accumulation (NAFL), progresses to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of lean NASH-HCC and how it differs from obese NASH-HCC is not well understood.
METHODS
In this work, we generated a mouse model of lean and obese NASH-HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to compare progression to NASH-HCC in lean versus obese mice. Comparisons were made at the organismal, histological, and molecular level by investigating fatty acid metabolism in the plasma of these mice.
RESULTS
Obese mice showed more pronounced glucose intolerance and insulin resistance, higher levels of plasma cholesterol and triglycerides, and higher penetrance of NASH compared to lean mice. Despite the abnormal metabolic profile of obese mice, male obese and lean mice developed HCC with similar penetrance (53.3% and 53.8%, respectively), albeit lean mice showed faster tumor progression as evidenced by the larger tumor size and lower HCC-free survival. None of the female lean mice developed HCC, while 50% of female obese mice developed HCC. Both groups of mice showed a reduction in plasma polyunsaturated fatty acids (PUFAs), however, the levels were higher towards the endpoint in obese mice compared to lean mice.
CONCLUSIONS
Unhealthy diet composition appears to drive progression to NASH-HCC rather than the organismal effects of obesity. PUFA levels may increase due to systemic inflammation in obese mice and act as suppressors of tumor progression, thus delaying HCC progression in obese mice compared to lean mice. These models could be used to further dissect the molecular pathogenesis of lean and obese NASH-HCC and address the mechanisms whereby PUFAs may be implicated in hepatocarcinogenesis.
Topics: Animals; Carcinoma, Hepatocellular; Cholesterol; Choline; Diet, High-Fat; Disease Models, Animal; Disease Progression; Female; Fructose; Liver; Liver Neoplasms; Male; Mice; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity
PubMed: 35994501
DOI: 10.1371/journal.pone.0272623 -
BMC Infectious Diseases Jun 2023To explore correlation between the dose of norepinephrine and the timing of starting enteral nutrition in septic shock (SS) patients.
BACKGROUND
To explore correlation between the dose of norepinephrine and the timing of starting enteral nutrition in septic shock (SS) patients.
METHODS
Totally 150 SS patients treated with enteral nutrition (EN) in Shiyan People's Hospital from Dece20 to July 2022 were included in this retrospective analysis. Patients were divided into tolerance group (n = 97) and intolerance group (n = 53) according to whether EN was tolerated or not. The study indexes include baseline characteristics [gender, age, weight, body mass index (BMI), scores of acute physiology and chronic health evaluation II system (APACHE II), comorbidity, time in-hospital, prognosis], clinical indexes [mean arterial pressure (MAP), time of mechanical ventilation (MV), norepinephrine dose at the time of starting EN, using of sedative drug, gastrointestinal motility drugs and cardiotonic drugs], EN indexes (timing of starting EN, speed of EN infusion, calorie of EN per day, EN target percent), and gastrointestinal intolerance index [residual gastric volume > 250 ml, vomiting, aspiration, gastrointestinal bleeding, blood lactic acid (BLA)]. Student-t test and Mann-Whitney test were used for test of measurement data. Chi-square test and fisher exact test were used for comparison of categorical data.
RESULTS
There were 51 (52.58%) male and 46 (47.42%) female patients with a median age of 66.4 ± 12.8 years old in tolerance group. There were 29 (54.72%) male and 24 (45.28%) female patients with a median age 67.3 ± 12.5 years old in intolerance group. The weight and BMI were significantly higher in intolerance group than those of tolerance group (both P < 0.001). There was no significant difference of comorbidity rate between two groups (all P > 0.05). Before the overlapping time of EN and norepinephrine, there were significantly more patients receiving gastrointestinal motility drugs in intolerance group compared with tolerance group (58.49% vs. 20.62%, P < 0.001). Patients in tolerance group had significantly less residual volume in gastric than that of intolerance group (188.00 ± 52.32 vs. 247.83 ± 34.95, P < 0.001). The rate of residual volume in gastric > 250ml (9.28% vs. 37.74%, P < 0.001), vomiting (15.46% vs. 35.85%, P = 0.004) and aspiration(16.49% vs. 33.96%, P = 0.018) were significantly lower in tolerance group than those of intolerance group. The BLA in tolerance group was significantly lower than that of intolerance group (1.84 ± 0.63 vs. 2.90 ± 1.5 3mmol/L,P < 0.001). There were significantly more patients with increased BLA (75.47% vs. 30.93%, P < 0.001) and > 2mmol BLA rising (43.40% vs. 8.25%, P < 0.001) in intolerance group than those of tolerance group. Patients in tolerance group had significantly lower time of starting EN (40.97 ± 9.53 vs. 49.85 ± 11.61 h, P < 0.001), dose of NE(0.23 ± 0.07 vs. 0.28 ± 0.10 ug/kg/min, P = 0.049), mortality in hospital (18.56% vs. 49.06%, P < 0.001) and mortality in ICU (16.49% vs. 37.74%, P < 0.001) compared with intolerance group. The EN target percent (92.78% vs. 56.60%, P < 0.001) and calorie of EN during overlapping period (20.22 ± 5.99 vs. 16.21 ± 2.52 kcal/kg/day, P < 0.001) in tolerance group were significantly higher than those of intolerance group.
CONCLUSIONS
SS patients should be comprehensively evaluated according to their condition. Obese patients are more prone to EN intolerance, and those who can tolerate EN should be implemented as soon as possible. The use dose of NE is significantly related to EN tolerance. When the use dose is low, EN tolerance is greater.
Topics: Humans; Male; Female; Middle Aged; Aged; Enteral Nutrition; Norepinephrine; Shock, Septic; Retrospective Studies; Intensive Care Units; Prognosis; Vomiting
PubMed: 37291494
DOI: 10.1186/s12879-023-08366-x -
BMJ Open Diabetes Research & Care Sep 2021Uncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is β-cell failure or insulin resistance (IR). Therefore, we... (Observational Study)
Observational Study
INTRODUCTION
Uncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is β-cell failure or insulin resistance (IR). Therefore, we determined the prevalence, phenotype and characteristics of Abnl-GT due to β-cell failure versus IR in 486 African-born blacks (male: 64%, age: 38±10 years (mean±SD)) living in America.
RESEARCH DESIGN AND METHODS
Oral glucose tolerance test were performed. Abnl-GT is a term which includes both diabetes and prediabetes and was defined as fasting plasma glucose (FPG) ≥5.6 mmol/L and/or 2-hour glucose ≥7.8 mmol/L. IR was defined by the lowest quartile of the Matsuda Index (≤2.98) and retested using the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR) (≥2.07). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell failure was defined as Abnl-GT without IR. Beta-cell compensation was assessed by the Disposition Index (DI). Fasting lipids were measured. Visceral adipose tissue (VAT) volume was obtained with abdominal CT scan.
RESULTS
The prevalence of Abnl-GT was 37% (182/486). For participants with Abnl-GT, IR occurred in 38% (69/182) and β-cell failure in 62% (113/182). Compared with Africans with Abnl-GT-IR, Africans with Abnl-GT-β-cell failure had lower body mass index (BMI) (30.8±4.3 vs 27.4±4.0 kg/m), a lower prevalence of obesity (52% vs 19%), less VAT (163±72 vs 107±63 cm), lower triglyceride (1.21±0.60 vs 0.85±0.42 mmol/L) and lower FPG (5.9±1.4 vs 5.3±0.6 mmol/L) and 2-hour glucose concentrations (10.0±3.1 vs 9.0±1.9 mmol/L) (all p<0.001) and higher DI, high-density lipoprotein (HDL), low-density lipoprotein particle size and HDL particle size (all p<0.01). Analyses with Matsuda Index and HOMA-IR yielded similar results. Potential confounders such as income, education, alcohol and fiber intake did not differ by group.
CONCLUSIONS
Beta-cell failure occurred in two-thirds of participants with Abnl-GT and may be a more frequent determinant of Abnl-GT in Africans than IR. As BMI category, degree of glycemia and lipid profile appeared more favorable when Abnl-GT was due to β-cell failure rather than IR, the clinical course and optimal interventions may differ.
TRIAL REGISTRATION NUMBER
NCT00001853.
Topics: Adult; Blood Glucose; Female; Glucose Intolerance; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged
PubMed: 34531244
DOI: 10.1136/bmjdrc-2021-002447 -
Journal of Diabetes Investigation Sep 2020Although moderate alcohol consumption lowers the risk of type 2 diabetes in European populations, the same cannot be assumed for Japanese patients with diabetes related...
AIMS/INTRODUCTION
Although moderate alcohol consumption lowers the risk of type 2 diabetes in European populations, the same cannot be assumed for Japanese patients with diabetes related to low insulin secretion rather than resistance. We aimed to evaluate the effects of daily alcohol consumption on glucose tolerance and diabetes development risk in Japanese populations.
MATERIALS AND METHODS
This retrospective study randomly enrolled 452 men and 659 women aged 40-78 years in 2005 (Gifu, Japan). The participants completed a 75-g oral glucose tolerance test and medical questionnaire. The homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function and insulinogenic index were used to estimate insulin sensitivity and secretion. The relationships between alcohol consumption and these parameters were analyzed using logistic regression after adjusting for potential confounders. The 5-year changes in hemoglobin A1c levels were also evaluated.
RESULTS
The adjusted odds ratios for elevated homeostasis model assessment of β-cell function values (<40%) in the 0-19.9 g/day, 20.0-39.9 g/day and ≥ 40 g/day alcohol consumption groups were 0.98, 1.46 and 2.68, respectively. Alcohol consumption induced a significant decrease in the insulin secretion level among the ≥40 g/day drinkers, especially in men. However, there was no risk of increased insulin resistance based on the homeostasis model assessment of insulin resistance (<2.5) results. The 5-year risk of elevated hemoglobin A1c levels (≥6.5%) was increased according to increase in alcohol consumption in both men and women.
CONCLUSIONS
Daily alcohol consumption was associated with reduced insulin secretion and an increased diabetes development risk in Japanese populations.
Topics: Adult; Aged; Alcohol Drinking; Biomarkers; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucose Intolerance; Humans; Insulin Secretion; Japan; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors
PubMed: 32227447
DOI: 10.1111/jdi.13260 -
United European Gastroenterology Journal Feb 2021Inability to advance to an oral diet, or oral feeding intolerance, is a common complication in patients with acute pancreatitis associated with worse clinical outcomes....
BACKGROUND
Inability to advance to an oral diet, or oral feeding intolerance, is a common complication in patients with acute pancreatitis associated with worse clinical outcomes. The factors related to oral feeding intolerance are not well studied.
OBJECTIVE
We aimed to determine the incidence and risk factors of oral feeding intolerance in acute pancreatitis.
METHODS
Patients were prospectively enrolled in the Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience, an international acute pancreatitis registry, between 2015 and 2018. Oral feeding intolerance was defined as worsening abdominal pain and/or vomiting after resumption of oral diet. The timing of the initial feeding attempt was stratified based on the day of hospitalization. Multivariable logistic regression was performed to assess for independent risk factors/predictors of oral feeding intolerance.
RESULTS
Of 1233 acute pancreatitis patients included in the study, 160 (13%) experienced oral feeding intolerance. The incidence of oral feeding intolerance was similar irrespective of the timing of the initial feeding attempt relative to hospital admission day (p = 0.41). Patients with oral feeding intolerance were more likely to be younger (45 vs. 50 years of age), men (61% vs. 49%), and active alcohol users (44% vs. 36%). They also had higher blood urea nitrogen (20 vs. 15 mg/dl; p < 0.001) and hematocrit levels (41.7% vs. 40.5%; p = 0.017) on admission; were more likely to have a nonbiliary acute pancreatitis etiology (69% vs. 51%), systemic inflammatory response syndrome of 2 or greater on admission (49% vs. 35%) and at 48 h (50% vs. 26%), develop pancreatic necrosis (29% vs. 13%), moderate to severe acute pancreatitis (41% vs. 24%), and have a longer hospital stay (10 vs. 6 days; all p < 0.04). The adjusted analysis showed that systemic inflammatory response syndrome of 2 or greater at 48 h (odds ratio 3.10; 95% confidence interval 1.83-5.25) and a nonbiliary acute pancreatitis etiology (odds ratio 1.65; 95% confidence interval 1.01-2.69) were independent risk factors for oral feeding intolerance.
CONCLUSION
Oral feeding intolerance occurs in 13% of acute pancreatitis patients and is independently associated with systemic inflammatory response syndrome at 48 h and a nonbiliary etiology.
Topics: Abdominal Pain; Adult; Age Factors; Alcohol Drinking; Blood Urea Nitrogen; Eating; Female; Food Intolerance; Hematocrit; Humans; Length of Stay; Male; Middle Aged; Pancreatitis; Prospective Studies; ROC Curve; Regression Analysis; Risk Factors; Sex Factors; Smoking; Vomiting
PubMed: 32883182
DOI: 10.1177/2050640620957243 -
Biomedicines May 2024Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and...
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS).
METHODS
This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab = 31; omalizumab = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS).
RESULTS
ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly ( < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD).
CONCLUSIONS
This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.
PubMed: 38790987
DOI: 10.3390/biomedicines12051025 -
Acta Biochimica Et Biophysica Sinica Jun 2020Alcoholism leads to organ injury including mitochondrial defect and apoptosis with evidence favoring a role for autophagy dysregulation in alcoholic damage. Parkin...
Alcoholism leads to organ injury including mitochondrial defect and apoptosis with evidence favoring a role for autophagy dysregulation in alcoholic damage. Parkin represents an autosomal recessive inherited gene for Parkinson's disease and an important member of selective autophagy for mitochondria. The association between Parkinson's disease and alcoholic injury remains elusive. This study aimed to examine the effect of parkin deficiency on chronic alcohol intake-induced organ injury in brain, liver and skeletal muscle (rectus femoris muscle). Adult parkin-knockout (PRK-/-) and wild-type mice were placed on Liber-De Carli alcohol liquid diet (4%) for 12 weeks prior to assessment of liver enzymes, intraperitoneal glucose tolerance, protein carbonyl content, apoptosis, hematoxylin and eosin morphological staining, and mitochondrial respiration (cytochrome c oxidase, NADH:cytochrome c reductase and succinate:cytochrome c reductase). Autophagy protein markers were monitored by western blot analysis. Our data revealed that chronic alcohol intake imposed liver injury as evidenced by elevated aspartate aminotransferase and alanine transaminase, glucose intolerance, elevated protein carbonyl formation, apoptosis, focal inflammation, necrosis, microvesiculation, autophagy/mitophagy failure and dampened mitochondrial respiration (complex IV, complexes I and III, and complexes II and III) in the brain, liver and rectus femoris skeletal muscle. Although parkin ablation itself did not generate any notable effects on liver enzymes, insulin sensitivity, tissue carbonyl damage, apoptosis, tissue morphology, autophagy or mitochondrial respiration, it accentuated alcohol intake-induced tissue damage, apoptosis, morphological change, autophagy/mitophagy failure and mitochondrial injury without affecting insulin sensitivity. These data suggest that parkin plays an integral role in the preservation against alcohol-induced organ injury, apoptosis and mitochondrial damage.
Topics: Alcohol Drinking; Animals; Autophagy; Brain; Liver; Mice; Mice, Knockout; Muscle, Skeletal; Ubiquitin-Protein Ligases
PubMed: 32427312
DOI: 10.1093/abbs/gmaa041