Dissociation Between Long-term Weight Loss Intervention and Blood Pressure: an 18-month Randomized Controlled Trial.

BACKGROUND: Obesity is associated with elevated blood pressure (BP). In patients with obesity and hypertension, weight loss lowers BP, but the long-term effect of weight loss on BP is less clear. OBJECTIVE: We aimed to assess the effect of long-term weight loss intervention on BP in normotensive and hypertensive subjects. DESIGN: Randomized controlled trial. PARTICIPANTS: Two hundred seventy-eight subjects (mean age 47.9 ± 9.3 years, 89% male, 56% hypertensive) with abdominal obesity or elevated serum triglycerides and low high-density lipoprotein cholesterol were recruited. INTERVENTION: Eighteen-month weight loss intervention. MAIN MEASURES: Body weight and BP were measured at baseline, after 6 and 18 months. RESULTS: After 6 months of intervention, in the weight loss phase, body mass index (BMI) decreased by an average of -2.2±1.5 kg/m2 (p<0.001) and both diastolic BP (DBP) and systolic BP (SBP) decreased by -2.1±8.8 mmHg and -2.3±12.9 mmHg, respectively (p<0.01 for both). The change in BMI was similar in normotensive and hypertensive subjects (-2.0±1.6 and -2.3±1.5, p = 0.246). However, DBP and SBP decreased significantly (-5.2±7.1 mmHg and -6.2±12.5 mmHg, respectively, p<0.001 for both) in hypertensive subjects, and increased in normotensive subjects (1.8±9.3 mmHg, p = 0.041 and 2.7±11.7 mmHg, p = 0.017, respectively). After 18 months, in the weight maintenance phase, BMI slightly increased (0.9±1.3 kg/m2, p<0.001) but remained significantly lower than at baseline (p<0.0001). Unlike BMI, DBP and SBP increased significantly in hypertensive subjects (p<0.001) and returned almost to baseline levels. CONCLUSION: Weight-loss intervention reduced BP in hypertensive patients, but this was not maintained in the long run. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01530724.

Effects of lifestyle interventions on epigenetic signatures of liver fat: Central randomized controlled trial.

BACKGROUND AND AIMS: In the CENTRAL trial context, we found diverse liver fat dynamics in response to different dietary interventions. Epigenetic mechanisms may contribute to the intraindividual variation. Moreover, genetic factors are involved in developing nonalcoholic fatty-liver disease (NAFLD), a disease reflected by an increase in intrahepatic fat (IHF). In this exploratory analysis, we primarily aimed to examine the effect of lifestyle interventions on DNA-methylation of NAFLD related genes associated with IHF. METHODS: For 120 participants from the CENTRAL trial, an 18-month regimen of either low-fat (LF) or Mediterranean-low carbohydrate (MED/LC) diets, with or without physical activity (PA+/PA-), was instructed. Magnetic resonance imaging was used to measure IHF%, which was analysed for association with CpG specific DNA-methylation levels of 41 selected candidate genes. Single-nucleotide polymorphisms known to be associated with NAFLD within the studied genes were genotyped by TaqMan assays. RESULTS: At baseline, participants (92% men; body mass index = 30.2 kg/m2 ) had mean IHF of 10.7% (59% NAFLD). Baseline-IHF% was inversely correlated with DNA-methylation at individual CpGs within AC074286.1, CRACR2A, A2MP1, FARP1 (P < .05 for all multivariate models). FARP1 rs9584805 showed association with IHF, with the prevalence of NAFLD and baseline methylation level of the CpG site (cg00071727) associated with IHF%. Following 18-month lifestyle intervention, differential DNA-methylation patterns were observed between diets at cg14335324 annotated to A2MP1 (P = .04, LF vs. MED/LC), and differential DNA-methylation between PA groups within AC074286.1, CRACR2A, and FARP1 CpGs (P < .05 for all, PA-vs. PA+). CONCLUSIONS: This study suggests epigenetic markers for IHF and potential epigenetic remodeling after long-term lifestyle interventions.

Atrial Fibrillation and Mortality in the Oldest Old after Surgery for Hip Fractures.

INTRODUCTION: One-year mortality following hip fractures increases steeply with age, from 2% in the 60- to 69-year-old population up to 28% in the oldest old (older than 90 years). Of the various factors that contribute to hip fractures, atrial fibrillation (AF) is an independent risk factor at any age. OBJECTIVE: The objective of this study was to assess the association of AF with mortality among the oldest old with hip fractures. METHOD: This is a retrospective cohort study of 701 persons above age 90 years who underwent orthopedic repair for a hip fracture during 2000-2018. Of them, 218 (31%) had AF at hospital admission. The primary outcome was survival following surgery. We compared patient characteristics and 30-day, 180-day, 1-year, and 3-year survival between patients with and without AF. RESULTS: The adjusted odds ratio for 30-day postoperative mortality for those with AF versus without AF group was 1.03 (95% confidence interval [CI] 0.63-1.66). Survival estimates were higher among those without AF than with AF at 180 days postoperative: 0.85 (95% CI 0.82-0.89) versus 0.68 (95% CI 0.61-0.74), p < 0.001; at 1 year postoperative: 0.68 (95% CI 0.63-0.72) versus 0.48 (95% CI 0.42-0.55), p < 0.001; and at 3 years postoperative: 0.47 (95% CI 0.42-0.52) versus 0.28 (95% CI 0.27-0.34), p < 0.001. CONCLUSIONS: Among individuals aged >90 years, operated for hip fractures, mortality was similar for those with and without AF at 30 days postoperative. However, the survival curves diverged sharply after 180 days. Our findings suggest that AF is not an immediate surgical risk factor, but rather confers increased long-term risk in this population.

Does the physician in triage strategy improve door-to-balloon time for patients with STEMI?

BACKGROUND: The physician in triage (PIT) strategy was implemented in the emergency department (ED) of the Soroka University Medical Center (SUMC) to improve overcrowding and waiting time. Our objective in the current study was to assess the impact of the PIT strategy on door-to-balloon time for the treatment of acute ST-elevation myocardial infarction (STEMI). METHODS: The PIT programme began on January 2016, working weekdays between 8:00 and 23:00 hours. We included patients who visited the ED and were diagnosed with STEMI, from November 2014 to February 2018. The primary outcome was improvement in door-to-balloon (D2B) time <90 min between the preintervention and postintervention period. The analysis included a comparison between the two time periods using univariate tests, a time trend analysis illustrated by the locally weighted scatterplot smoothing curves and a regression analysis using generalised estimating equation models. To determine the impact of the PIT, as opposed to other changes in the department, we stratified the population arriving after January 2016 to patients arriving during PIT hours versus patients arriving on weekends and at nights (23:00-8:00 hours). RESULTS: In all, 415 patients met all the inclusion criteria of which 237 (57.1%) visited on weekdays 8:00-23:00 hours. The per cent of patients with D2B <90 min was 13.9% higher for postintervention versus preintervention visits (p=0.006). D2B time was significantly shorter by 9 min for postintervention visits (p=0.001). In the postintervention period, patients arriving between 8:00 and 23:00 hours on weekdays were more likely to have D2B <90 min than those arriving nights and weekends; 90/146 (61.6%) vs 47.2% (51/108), respectively, p=0.02. ORs for D2B <90 min was 2.04 (95% CI 1.06 to 3.91) for weekday visits, and 1.90 (0.88 to 4.12) for weekend and night visits. CONCLUSION: The PIT model in SUMC is associated with D2B reduction for patients with STEMI. To achieve further reduction, both targeted interventions should be performed and PIT strategy should be applied for full time, including nights and weekends.

Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial.

BACKGROUND: We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots. METHODS: We performed an 18-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to isocaloric low-fat or Mediterranean/low-carbohydrate (MED/LC) diet+28 g walnuts/day with/without added moderate physical activity (PA; 80% aerobic; supervised/free gym membership). Overall primary outcome was body fat redistribution, and the main specific end point was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots (deep and superficial subcutaneous, liver, pericardial, muscle, pancreas, and renal sinus) by magnetic resonance imaging. RESULTS: Of 278 participants (age, 48 years, 89% men, body mass index, 30.8 kg/m2), 86% completed the trial with good adherence. The low-fat group preferentially decreased reported fat intake (-21.0% versus -11.5% for the MED/LC; P<0.001), and the MED/LC group decreased reported carbohydrates intake (-39.5% versus -21.3% for the low-fat group; P<0.001). The PA+ groups significantly increased the metabolic equivalents per week versus the PA- groups (19.0 versus 2.1; P=0.009). Whereas final moderate weight loss was indifferent, exercise attenuated the waist circumference rebound with the greatest effect in the MED/LCPA+ group (P<0.05). VAT (-22%), intrahepatic (-29%), and intrapericardial (-11%) fats declines were higher than pancreatic and femur intermuscular fats (1% to 2%) loss. Independent of weight loss, PA+ with either diet had a significantly greater effect on decreasing VAT (mean of difference, -6.67cm2; 95% confidence interval, -14.8 to -0.45) compared with PA-. The MED/LC diet was superior to the low-fat diet in decreasing intrahepatic, intrapericardial, and pancreatic fats (P<0.05 for all). In contrast, renal sinus and femoral intermuscular fats were not differentially altered by lifestyle interventions but by weight loss per se. In multivariate models further adjusted for weight loss, losing VAT or intrahepatic fat was independently associated with improved lipid profile, losing deep subcutaneous adipose tissue with improved insulin sensitivity, and losing superficial subcutaneous adipose tissue remained neutral except for an association with decreased leptin. CONCLUSIONS: Moderate weight loss alone inadequately reflects the significant lifestyle effects on atherogenic and diabetogenic fat depots. The MED/LC diet mobilizes specific ectopic fat depots, and exercise has an independent contribution to VAT loss. Fat depots exhibit diverse responsiveness and are differentially related to cardiometabolic markers. Distinct lifestyle protocols may uniquely induce fat mobilization from specific anatomic sites. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01530724.

The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content.

BACKGROUND & AIM: It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes. METHODS: In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months. RESULTS: Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (-6.6% absolute units [-41% relatively]) and 18 months (-4.0% absolute units [-29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes. CONCLUSIONS: %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss. LAY SUMMARY: High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724.

HNF1A variant, energy-reduced diets and insulin resistance improvement during weight loss: The POUNDS Lost trial and DIRECT.

AIM: To determine whether weight-loss diets varying in macronutrients modulate the genetic effect of hepatocyte nuclear factor 1α (HNF1A) rs7957197 on weight loss and improvement of insulin resistance. MATERIALS AND METHODS: We analysed the interaction between HNF1A rs7957197 and weight-loss diets with regard to weight loss and insulin resistance improvement among 722 overweight/obese adults from a 2-year randomized weight-loss trial, the POUNDS Lost trial. The findings were replicated in another independent 2-year weight-loss trial, the Dietary Intervention Randomized Controlled Trial (DIRECT), in 280 overweight/obese adults. RESULTS: In the POUNDS Lost trial, we found that a high-fat diet significantly modified the genetic effect of HNF1A on weight loss and reduction in waist circumference (P for interaction = .006 and .005, respectively). Borderline significant interactions for fasting insulin and insulin resistance (P for interaction = .07 and .06, respectively) were observed. We replicated the results in DIRECT. Pooled results showed similar significant interactions with weight loss, waist circumference reduction, and improvement in fasting insulin and insulin resistance (P values for interaction = .001, .005, .02 and .03, respectively). Greater decreases in weight, waist circumference, fasting insulin level and insulin resistance were observed in participants with the T allele compared to those without the T allele in the high-fat diet group (P = .04, .03 and .01, respectively). CONCLUSIONS: Our replicable findings provide strong evidence that individuals with the HNF1A rs7957197 T allele might obtain more benefits in weight loss and improvement of insulin resistance by choosing a hypocaloric and high-fat diet.

Intrahepatic fat, abdominal adipose tissues, and metabolic state: magnetic resonance imaging study.

BACKGROUND: Intrahepatic fat (IHF) is best known to associate with waist circumference (WC) and visceral adipose tissue (VAT), but its relation to abdominal subcutaneous adipose tissue is controversial. While IHF ≥ 5% dichotomously defines fatty liver, %IHF is rarely considered as a continuous variable that includes the normal range. In this study, we aimed to evaluate %IHF association with abdominal fat subdepots, pancreatic, and renal-sinus fats. METHODS: We evaluated %IHF, abdominal fat subdepots, %pancreatic, and renal-sinus fats, among individuals with moderate abdominal obesity, using 3-Tesla magnetic resonance imaging. RESULTS: Among 275 participants, %IHF widely ranged (0.01%-50.4%) and was lower in women (1.6%) than men (7.3%; P < .001). In an age, sex, and WC-adjusted models, VAT area (P < .006) was directly associated with %IHF, while superficial-subcutaneous adipose tissue proportion was inversely associated with %IHF (P < .006). In these models, renal-sinus fat was positively associated with %IHF (P = .005). In an age, sex, WC, and VAT-adjusted models, elevated liver enzymes, glycemic, lipid, and inflammatory biomarkers were associated with increased %IHF (P < .003 for all). In these models, the associations remained robust even within the normal range strata of IHF < 5% for triglycerides and chemerin (P ≤ .004 for all). For the diagnosis of fatty liver, the joint area under the curve of WC, alanine-aminotransferase, triglycerides/high-density lipoprotein cholesterol, and homeostasis model assessment of insulin resistance was 0.84(95% CI, 0.79-0.89). CONCLUSIONS: Intrahepatic fat is differentially associated with abdominal fat subdepots. Intrahepatic-fat as a continuous variable could be predicted by specific traditional parameters, even within the current normal range, and partially independent of VAT.

Effects of initiating moderate wine intake on abdominal adipose tissue in adults with type 2 diabetes: a 2-year randomized controlled trial.

OBJECTIVE: To generate evidence-based conclusions about the effect of wine consumption on weight gain and abdominal fat accumulation and distribution in patients with type 2 diabetes. DESIGN: In the 2-year randomized controlled CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, patients following a Mediterranean diet were randomly assigned to drink 150 ml of mineral water, white wine or red wine with dinner for 2 years. Visceral adiposity and abdominal fat distribution were measured in a subgroup of sixty-five participants, using abdominal MRI. SETTING: Ben-Gurion University of the Negev, Soroka-Medical Center and the Nuclear Research Center Negev, Israel. SUBJECTS: Alcohol-abstaining adults with well-controlled type 2 diabetes. RESULTS: Forty-eight participants (red wine, n 27; mineral water, n 21) who completed a second MRI measurement were included in the 2-year analysis. Similar weight losses (sd) were observed: red wine 1·3 (3·9) kg; water 1·0 (4·2) kg (P=0·8 between groups). Changes (95 % CI) in abdominal adipose-tissue distribution were similar: red wine, visceral adipose tissue (VAT) -3·0 (-8·0, 2·0) %, deep subcutaneous adipose tissue (DSAT) +5·2 (-1·1, 11·6) %, superficial subcutaneous adipose tissue (SSAT) -1·9 (-5·0, 1·2) %; water, VAT -3·2 (-8·9, 2·5) %, DSAT +2·9 (-2·8, 8·6) %, SSAT -0·15 (-3·3, 2·9) %. No changes in antidiabetic medication and no substantial changes in energy intake (+126 (sd 2889) kJ/d (+30·2 (sd 690) kcal/d), P=0·8) were recorded. A 2-year decrease in glycated Hb (ß=0·28, P=0·05) was associated with a decrease in VAT. CONCLUSIONS: Moderate wine consumption, as part of a Mediterranean diet, in persons with controlled diabetes did not promote weight gain or abdominal adiposity.

Effects of Initiating Moderate Alcohol Intake on Cardiometabolic Risk in Adults With Type 2 Diabetes: A 2-Year Randomized, Controlled Trial.

BACKGROUND: Recommendations for moderate alcohol consumption remain controversial, particularly in type 2 diabetes mellitus (T2DM). Long-term randomized, controlled trials (RCTs) are lacking. OBJECTIVE: To assess cardiometabolic effects of initiating moderate alcohol intake in persons with T2DM and whether the type of wine matters. DESIGN: 2-year RCT (CASCADE [CArdiovaSCulAr Diabetes & Ethanol] trial). (ClinicalTrials.gov: NCT00784433). SETTING: Ben-Gurion University of the Negev-Soroka Medical Center and Nuclear Research Center Negev, Israel. PATIENTS: Alcohol-abstaining adults with well-controlled T2DM. INTERVENTION: Patients were randomly assigned to 150 mL of mineral water, white wine, or red wine with dinner for 2 years. Wines and mineral water were provided. All groups followed a Mediterranean diet without caloric restriction. MEASUREMENTS: Primary outcomes were lipid and glycemic control profiles. Genetic measurements were done, and patients were followed for blood pressure, liver biomarkers, medication use, symptoms, and quality of life. RESULTS: Of the 224 patients who were randomly assigned, 94% had follow-up data at 1 year and 87% at 2 years. In addition to the changes in the water group (Mediterranean diet only), red wine significantly increased high-density lipoprotein cholesterol (HDL-C) level by 0.05 mmol/L (2.0 mg/dL) (95% CI, 0.04 to 0.06 mmol/L [1.6 to 2.2 mg/dL]; P < 0.001) and apolipoprotein(a)1 level by 0.03 g/L (CI, 0.01 to 0.06 g/L; P = 0.05) and decreased the total cholesterol-HDL-C ratio by 0.27 (CI, -0.52 to -0.01; P = 0.039). Only slow ethanol metabolizers (alcohol dehydrogenase alleles [ADH1B*1] carriers) significantly benefited from the effect of both wines on glycemic control (fasting plasma glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c) compared with fast ethanol metabolizers (persons homozygous for ADH1B*2). Across the 3 groups, no material differences were identified in blood pressure, adiposity, liver function, drug therapy, symptoms, or quality of life, except that sleep quality improved in both wine groups compared with the water group (P = 0.040). Overall, compared with the changes in the water group, red wine further reduced the number of components of the metabolic syndrome by 0.34 (CI, -0.68 to -0.001; P = 0.049). LIMITATION: Participants were not blinded to treatment allocation. CONCLUSION: This long-term RCT suggests that initiating moderate wine intake, especially red wine, among well-controlled diabetics as part of a healthy diet is apparently safe and modestly decreases cardiometabolic risk. The genetic interactions suggest that ethanol plays an important role in glucose metabolism, and red wine's effects also involve nonalcoholic constituents. PRIMARY FUNDING SOURCE: European Foundation for the Study of Diabetes.

CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials.

Little is known about whether cholesteryl ester transfer protein (CETP) genetic variation may modify the effect of weight-loss diets varying in fat content on changes in lipid levels. We analyzed the interaction between the CETP variant rs3764261 and dietary interventions on changes in lipid levels among 732 overweight/obese adults from a 2 year randomized weight-loss trial [Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST)], and replicated the findings in 171 overweight/obese adults from an independent 2 year weight-loss trial [Dietary Intervention Randomized Controlled Trial (DIRECT)]. In the POUNDS LOST, participants with the CETP rs3764261 CC genotype on the high-fat diet had larger increases in HDL cholesterol (P = 0.001) and decreases in triglycerides (P = 0.007) than those on the low-fat diet at 6 months, while no significant difference between these two diets was observed among participants carrying other genotypes. The gene-diet interactions on changes in HDL-cholesterol and tri-glyc-erides were replicated in the DIRECT (pooled P for interaction ≤ 0.01). Similar results on trajectory of changes in HDL cholesterol and triglycerides over the 2 year intervention were observed in both trials. Our study provides replicable evidence that individuals with the CETP rs3764261 CC genotype might derive greater effects on raising HDL cholesterol and lowering triglycerides by choosing a low-carbohydrate/high-fat weight-loss diet instead of a low-fat diet.

Effect of changes in food groups intake on magnesium, zinc, copper, and selenium serum levels during 2 years of dietary intervention.

BACKGROUND: Essential elements in serum are related to specific changes in food groups intake. OBJECTIVE: To address the effect of 2-year food intake changes in an intervention study on serum concentrations of magnesium, zinc, copper, and selenium. METHOD: Two hundred thirty-one participants, a subgroup of the Dietary Intervention Randomized Control Trial (DIRECT) study (age = 52 years; body mass index = 32.8 kg/m(2); 85% males) randomized to low-fat, Mediterranean, or low-carbohydrate diets in a 2-year dietary intervention trial were followed for serum concentrations determined using inductively coupled plasma-mass spectrometry. Changes in the intake of 11 food groups were evaluated by food frequency questionnaires. RESULTS: Using multivariate regression models, adjusted for age, sex, baseline body weight (kg), and changes in intakes of 11 food groups (g/d), at 12 months, serum element elevations were observed mainly in the low-carbohydrate group: selenium, by increasing consumption of fats and oils (ß = 0.415, p = 0.009) and legumes (ß = 0.183, p = 0.010) and decreasing fruit intake (ß = -0.438, p = 0.030); copper, by increasing consumption of legumes (ß = 0.453, p = 0.018) and dairy products (ß = 0.320, p = 0.039); magnesium by increasing fish consumption (ß = 0.374, p = 0.042) in the low-carbohydrate group and in the entire study population (ß = 0.237, p = 0.016); and zinc exclusively in the low-fat group by decreasing consumption of fats and oils (ß = -0.575, p = 0.022). At 24 months, serum elements were elevated mainly in the low-fat diet group, mostly by decreasing intake of snacks, sweets, and cakes: zinc (ß = -0.570, p = 0.027), copper (ß = -0.649, p = 0.012), and selenium (ß = -0.943, p < 0.001). Also in this group, magnesium levels were elevated by increasing vegetable intake (ß = 0.395, p = 0.041), copper by increasing fruit intake (ß = 0.375, p = 0.025), and selenium by increasing consumption of bread, pasta, and cereals (ß = 0.751, p = 0.011). The entire group, further adjusted to assigned diet type, increased selenium (ß = 0.294, p = 0.004) and copper (ß = 0.220, p = 0.038) by increasing consumption of bread, pasta, and cereals; selenium level was also predicted by decreasing consumption of snacks, sweets, and cakes (ß = -0.256, p = 0.014). Introducing energy expenditure, expressed in metabolic equivalents (MET = 1 kcal·kg(-1)·h(-1)), as an additional variable emphasized the negative effect of sweets and cakes on increasing serum concentrations of zinc, copper, and selenium after 24 months (ß = -0.549, p = 0.021; ß = -0.669, p = 0.012; ß = -0.982, p < 0.001, respectively), especially in the low-fat diet group. No significant associations between changes in food groups intake and the 4 elements were found in the Mediterranean diet group. CONCLUSIONS: During this 2-year intervention, serum concentrations of 4 essential elements were associated with a diversity of food group intake patterns. Comprehensive predictors for elevating zinc, copper, and selenium in serum included decreasing consumption of sweets and cakes while increasing consumption of bread, cereals, and pasta.

Delirium screening in the emergency department: evaluation and intervention.

BACKGROUND: Between 8-17% of older adults, and up to 40% of those arriving from nursing homes, present with delirium upon admission to the Emergency Department (ED). However, this condition often remains undiagnosed by ED medical staff. We investigated the prevalence of delirium among patients aged 65 and older admitted to the ED and assessed the impact of a prospective study aimed at increasing awareness. METHODS: The study was structured into four phases: a "pre-intervention period" (T0); an "awareness period" (T1), during which information about delirium and its diagnosis was disseminated to ED staff; a "screening period" (T2), in which dedicated evaluators screened ED patients aged 65 and older; and a "post-intervention period" (T3), following the departure of the evaluators. Delirium screening was conducted using the Brief Confusion Assessment Method (bCAM) questionnaire. RESULTS: During the T0 and T1 periods, the rate of delirium diagnosed by ED staff was below 1%. The evaluators identified a delirium rate of 14.9% among the screened older adults during the T2 period, whereas the rate among those assessed by ED staff was between 1.6% and 1.9%. Following the evaluators' departure in the T3 period, the rate of delirium diagnosis decreased to 0.89%. CONCLUSIONS: This study underscores that a significant majority of older adult delirium cases remain undetected by ED staff. Despite efforts to increase awareness, the rate of diagnosis did not significantly improve. While the presence of dedicated delirium evaluators slightly increased the diagnosis rate among patients assessed by ED staff, this rate reverted to pre-intervention levels after the evaluators left. These findings emphasize the necessity of implementing mandatory delirium screening during ED triage and throughout the patient's stay.

Management of diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is an acute life-threatening emergency in patients with diabetes, it can result in serious morbidity and mortality. Management of DKA requires reversing metabolic derangements, correcting volume depletion, electrolyte imbalances and acidosis while concurrently treating the precipitating illness. There are still controversies regarding certain aspects of DKA management. Different society guidelines have inconsistencies in their recommendations, while some aspects of treatment are not precise enough or have not been thoroughly studied. These controversies may include issues such as optimal fluid resuscitation, rate and type of Insulin therapy, potassium and bicarbonate replacement. Many institutions follow common society guidelines, however, other institutions either develop their own protocols for internal use or do not routinely use any protocols, resulting in inconsistencies in treatment and increased risk of complications and suboptimal outcomes. The objectives of this article are to review knowledge gaps and controversies in the treatment of DKA and provide our perspective on these issues. Moreover, we believe that special patient factors and comorbidities should receive more careful attention and consideration. Factors like pregnancy, renal disease, congestive heart failure, acute coronary syndrome, older age, use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and site of care all impact the treatment approach and require tailored management strategies. However, guidelines often lack sufficient recommendations regarding specific conditions and comorbidities, we aim to address unique circumstances and provide an approach to managing complex patients with specific conditions and co-morbidities. We also sought to examine changes and trends in the treatment of DKA, illuminate on aspects of latest research with a perspective towards future developments and modifications.

[Physicians' strikes--ethical considerations].

Strikes in general represent a solution based on a form of coercion. Historically, the striker caused direct damage to his employer, who was responsible for the perceived unfair treatment of the employee. In the case of strikes in the public sector, the employer is generally not harmed, but innocent citizens suffer in order to pressure the government agencies, a questionable practice from an ethical viewpoint. Physicians' strikes have more serious ethical problems. They cause suffering and death to innocent citizens. They violate the ethical codes to which physicians have committed themselves as professionals, and they seriously impair the trust of the public in physicians. Better and more ethical ways to provide fair compensation for physicians must be employed, perhaps like those used for judges and members of the IDF.

Neutrophil to lymphocyte ratio as an early indicator for ureteral catheterization in patients with renal colic due to upper urinary tract lithiasis.

PURPOSE: To evaluate whether the neutrophil-to-lymphocyte ratio (NLR) can predict the need for ureteral catheterization in patients with renal colic. MATERIALS AND METHODS: We retrospectively studied 15,887 patients with renal colic between 2005 and 2019. Patients with prior antibiotics treatment (156), with hematological diseases (15), with negative computerized tomography scan (CTS) for stone disease (473) or with no available laboratory findings (1750) were excluded. A ureteral double J stent (DJS) was inserted in case of ongoing pain, fever, sepsis, single kidney and elevated blood creatinine levels concomitant with hydronephrosis. A cut-off value of 2.1 NLR was determined to stratify and to compare patients using multivariable logistic regression models. A locally weighted scatterplot smoothing (LOWESS) plot was also applied to show the relationship between NLR and predicted probability for DJS insertion. RESULTS: Thirteen-thousand and 493 patients with a mean age of 42.7 years (30% females and 70% males) were included in the study. Five-hundred and 57 patients (4.1%) underwent early DJS insertion: 5.3% vs. 1.5% of patients with high vs. low NLR, respectively, (p<0.001). High NLR was significantly associated with longer hospitalization time, admission to the intensive care unit and overall mortality within a month from admission (p<0.05). LOWESS plot showed that NLR value >2.1 escalates progressively the probability for DJS insertion. CONCLUSIONS: A high NLR is associated with the need for early internal DJS insertion due to urolithiasis. The NLR is easily calculated from simple blood tests and based on our results can be used for clinical decision making in patients with renal colic needing renal decompression.

Diabetic ketoacidosis in pregnancy - Case series, pathophysiology, and review of the literature.

OBJECTIVE: Diabetic ketoacidosis (DKA) during pregnancy is a life-threatening emergency for both the mother and the fetus. The pathophysiology of DKA in pregnancy has its own characteristics due to multiple factors, such as insulin resistance, accelerated starvation and respiratory alkalosis, thus creating ketosis-prone state, with DKA occurring at milder degrees of hyperglycemia, even in normoglycemic levels, which can result in delayed diagnosis and treatment with potential for adverse metabolic consequences. STUDY DESIGN: In this article, we presented 8 clinical cases of DKA during pregnancy. We discuss the spectrum of the clinical picture, the entity of euglycemic DKA vs hyperglycemic DKA, the period of pregnancy in appearance of episode of DKA and triggers of DKA. CONCLUSION: The treatment of DKA in pregnant women must be started immediately and must be accentuated on intravenous fluids, insulin and electrolyte replacement. DKA in pregnancy may be euglycemic. Prevention, early recognition, immediate hospitalization, and aggressive management remain the cornerstones in DKA management in pregnancy.

Dietary intervention to reverse carotid atherosclerosis.

BACKGROUND: It is currently unknown whether dietary weight loss interventions can induce regression of carotid atherosclerosis. METHODS AND RESULTS: In a 2-year Dietary Intervention Randomized Controlled Trial-Carotid (DIRECT-Carotid) study, participants were randomized to low-fat, Mediterranean, or low-carbohydrate diets and were followed for changes in carotid artery intima-media thickness, measured with standard B-mode ultrasound, and carotid vessel wall volume (VWV), measured with carotid 3D ultrasound. Of 140 complete images of participants (aged 51 years; body mass index, 30 kg/m(2); 88% men), higher baseline carotid VWV was associated with increased intima-media thickness, age, male sex, baseline weight, blood pressure, and insulin levels (P<0.05 for all). After 2 years of dietary intervention, we observed a significant 5% regression in mean carotid VWV (-58.1 mm(3;) 95% confidence interval, -81.0 to -35.1 mm(3); P<0.001), with no differences in the low-fat, Mediterranean, or low-carbohydrate groups (-60.69 mm(3), -37.69 mm(3), -84.33 mm(3), respectively; P=0.28). Mean change in intima-media thickness was -1.1% (P=0.18). A reduction in the ratio of apolipoprotein B(100) to apolipoprotein A1 was observed in the low-carbohydrate compared with the low-fat group (P=0.001). Participants who exhibited carotid VWV regression (mean decrease, -128.0 mm(3); 95% confidence interval, -148.1 to -107.9 mm(3)) compared with participants who exhibited progression (mean increase, +89.6 mm(3); 95% confidence interval, +66.6 to +112.6 mm(3)) had achieved greater weight loss (-5.3 versus -3.2 kg; P=0.03), greater decreases in systolic blood pressure (-6.8 versus -1.1 mm Hg; P=0.009) and total homocysteine (-0.06 versus +1.44 mumol/L; P=0.04), and a higher increase of apolipoprotein A1 (+0.05 versus -0.00 g/L; P=0.06). In multivariate regression models, only the decrease in systolic blood pressure remained a significant independent modifiable predictor of subsequent greater regression in both carotid VWV (beta=0.23; P=0.01) and intima-media thickness (beta=0.28; P=0.008) levels. CONCLUSIONS: Two-year weight loss diets can induce a significant regression of measurable carotid VWV. The effect is similar in low-fat, Mediterranean, or low-carbohydrate strategies and appears to be mediated mainly by the weight loss-induced decline in blood pressure. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique Identifier: NCT00160108.

Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.

BACKGROUND: Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates. METHODS: In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie. RESULTS: The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels). CONCLUSIONS: Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. (ClinicalTrials.gov number, NCT00160108.)

Effect of changes in the intake of weight of specific food groups on successful body weight loss during a multi-dietary strategy intervention trial.

BACKGROUND: Distinct weight loss dietary strategies are associated with changes in specific food groups. OBJECTIVE: To address the effect of changes in specific weight of food groups on weight loss in a 2-year low-fat, Mediterranean, low-carbohydrate intervention trial (DIRECT). METHODS: We assessed changes in the intake of 12 food groups among 322 participants (body mass index [BMI] = 31 kg/m(2); age = 52 years; 86% men), using a validated electronic food frequency questionnaire. RESULTS: The weight of the 3592.9 ± 1558 (g/d ± SD) of baseline food consumed consisted mainly of liquids, excluding water (32.6% of total weight of food); vegetables (18.8%), fruits (17.7%), dairy (9.0%), meat (7.7%), and bread/cereal/pasta/potatoes (7.1%). Participants significantly reduced food intake by 283.73 ± 1342 (g/d ± SD) at 6 months and by 963.36 ± 1869 (g/d ± SD) at 24 months (p < 0.05 as compared with baseline). Food weight changes were similar across diet groups (p = 0.366), whereas 6-month body weight loss was -4.6 ± 4.4 kg, -4.7 ± 4.9 kg, and -6.4 ± 6.6 kg for low-fat, Mediterranean, and low-carbohydrate groups, respectively; p < 0.026). In multivariate regression models, adjusted for age, sex, baseline body weight, and changes in weight intake of 12 food groups (g/d), independent dietary predictors (standardized-ß) at 6 months (rapid weight loss phase) were as follows: decreased consumption of sweets and cakes (ß = 0.493; p = 0.008) in the low-fat group, tendency toward increased crude legumes (ß = -0.196; p = 0.061) in the Mediterranean group, and increased vegetable intake (ß = -0.249; p = 0.018) in the low-carbohydrate diet group. In the entire group, in models further adjusted for diet type, leading predictors for rapid weight loss phase were as follows: increased vegetables by ~140 g/d (ß = -0.116; p = 0.045) and decreased intake of sweets and cakes by ~30 g/d (ß = 0.162; p = 0.010). Universal predictors for 2-year successful weight loss in the entire group were as follows: increased intake of vegetables (ß = -0.192; p = 0.007) and meat (ß = -0.146; p = 0.026) and decreased intake of eggs (ß = 0.187; p = 0.003), processed legumes (ß = 0.195; p = 0.002), and beverages (ß = 0.135; p = 0.032). CONCLUSIONS: Two-year weight loss is associated with a decrease of ~1 kg of total food consumed and may be achieved by a variety of changes in specific food groups within different diet strategies. Universal predictors of successful weight loss in the rapid weight loss phase across all diet strategies are increasing the weight of intake of vegetables and decreasing the weight of intake of sweets and cakes.