The Real-Life Use of a Protein-Sparing Modified Fast Diet by Nasogastric Tube (ProMoFasT) in Adults with Obesity: An Open-Label Randomized Controlled Trial.

BACKGROUND: Protein-sparing modified fast (PSMF) diet is a very-low-carbohydrate ketogenic diet administered to patients with obesity, which preserves lean mass and suppresses appetite as well as continuous enteral feeding. Thus, we aim to evaluate the effect of the PSMF diet administered continuously by nasogastric tube (NGT) or orally. METHODS: Patients with a body mass index (BMI) > 34.9 kg/m2 were randomly assigned to receive a whey protein PSMF formula through NGT (ProMoFasT) or orally. Data were collected at baseline and after 150 days. The endpoints were assessed in the intention-to-treat population. RESULTS: We enrolled 20 patients in the ProMoFasT group and 24 in the oral group. No differences in body weight, BMI or waist circumference between the two groups were found after 150 days. At follow-up, FFM (%) and MM (%) results were higher in the ProMoFasT group than the oral group (63.1% vs. 52.9%, p = 0.012 and 45.0% vs. 36.1%, p = 0.009, respectively) and FM (kg) and FM (%) were significantly lower in the ProMoFasT group (36.9 kg vs. 44.0 kg, p = 0.033 and 37.4% vs. 44.9%, p = 0.012, respectively). Insulin levels were lower in the ProMoFasT group than the oral group at follow-up (11.8 mU/L vs. 28.0 mU/L, p = 0.001, respectively). CONCLUSION: The ProMoFasT is more effective in improving body composition and glucometabolic markers than the same diet administered orally.

Immunonutrition in major oncologic head and neck surgery: Analysis of complications, plasmatic equilibrium, and costs.

BACKGROUND: Malnutrition, in patients with solid tumors, is associated with a worse clinical outcome and about 40% of patients affected by head and neck cancers (HNC) are malnourished at the time of cancer diagnosis. We investigated the potential benefit of a standardized immunonutritional protocol (INP) to patients with HNC receiving major ablative surgery. METHODS: An observational study was conducted enrolling 199 patients: 50 treated with the INP and 149 with standard enteral nutrition. Complication rates, need for medications, and costs were considered as outcomes. RESULTS: INP played a protective role in development of major surgical complications (OR 0.23, p = 0.023), albumin administration (RR 0.38, p = 0.018), and antibiotic duration (p < 0.001) and is cost-effective in patients with moderate or severe malnutrition (-6083€ and -11 988€, p < 0.05). CONCLUSIONS: Our study supports the utility of INP, and accurate nutritional screening can help to identify malnourished patients who would receive the most benefits from this protocol.

Safety and Feasibility of Fasting-Mimicking Diet and Effects on Nutritional Status and Circulating Metabolic and Inflammatory Factors in Cancer Patients Undergoing Active Treatment.

In preclinical studies, fasting was found to potentiate the effects of several anticancer treatments, and early clinical studies indicated that patients may benefit from regimes of modified fasting. However, concerns remain over possible negative impact on the patients' nutritional status. We assessed the feasibility and safety of a 5-day "Fasting-Mimicking Diet" (FMD) as well as its effects on body composition and circulating growth factors, adipokines and cyto/chemokines in cancer patients. In this single-arm, phase I/II clinical trial, patients with solid or hematologic malignancy, low nutritional risk and undergoing active medical treatment received periodic FMD cycles. The body weight, handgrip strength and body composition were monitored throughout the study. Growth factors, adipokines and cyto/chemokines were assessed by ELISA. Ninety patients were enrolled, and FMD was administered every three weeks/once a month with an average of 6.3 FMD cycles/patient. FMD was largely safe with only mild side effects. The patients' weight and handgrip remained stable, the phase angle and fat-free mass increased, while the fat mass decreased. FMD reduced the serum c-peptide, IGF1, IGFBP3 and leptin levels, while increasing IGFBP1, and these modifications persisted for weeks beyond the FMD period. Thus, periodic FMD cycles are feasible and can be safely combined with standard antineoplastic treatments in cancer patients at low nutritional risk. The FMD resulted in reduced fat mass, insulin production and circulating IGF1 and leptin. This trial was registered on Clinicaltrials.gov in July 2018 with the identifier NCT03595540.

Clinical efficacy of eucaloric ketogenic nutrition in the COVID-19 cytokine storm: A retrospective analysis of mortality and intensive care unit admission.

OBJECTIVES: Our primary objective was to explore the effect of a eucaloric ketogenic diet (EKD) on mortality, admission to the intensive care unit, and need for non-invasive ventilation in hospitalized patients with COronaVIrus Disease 19 (COVID-19), in comparison to a eucaloric standard diet. Secondary objectives were verification of the safety and feasibility of the diet and its effects on inflammatory parameters, particularly interleukin-6. METHODS: The study is a retrospective analysis of 34 patients fed with an EKD in comparison to 68 patients fed with a eucaloric standard diet, selected and matched using propensity scores 1:2 to avoid the confounding effect of interfering variables. Our hypothesis was that an EKD would reduce mortality, admission to the intensive care unit, and need for non-invasive ventilation in patients with COVID-19. RESULTS: The preliminary multivariate analysis showed a statistically significant difference in survival (P = 0.046) and need for the intensive care unit (P = 0.049) for the EKD compared with a eucaloric standard diet. Even considering the EKD start day as a time-dependent variable, the results maintain a positive trend for application of the diet, and it is not possible to reject the null hypothesis (P < 0.05). Interleukin-6 concentrations between t0 and t7 (7 d after the beginning of the diet) in the ketogenic nutrition group show a trend that is almost significant (P = 0.062). The EKD was safe and no adverse events were observed. CONCLUSIONS: These results show a possible therapeutic role of an EKD in the clinical management of COVID-19. Currently, a prospective controlled randomized trial is running to confirm these preliminary data.

Fasting-mimicking diet and hormone therapy induce breast cancer regression.

Approximately 75% of all breast cancers express the oestrogen and/or progesterone receptors. Endocrine therapy is usually effective in these hormone-receptor-positive tumours, but primary and acquired resistance limits its long-term benefit1,2. Here we show that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet3-5 enhances the activity of the endocrine therapeutics tamoxifen and fulvestrant by lowering circulating IGF1, insulin and leptin and by inhibiting AKT-mTOR signalling via upregulation of EGR1 and PTEN. When fulvestrant is combined with palbociclib (a cyclin-dependent kinase 4/6 inhibitor), adding periodic cycles of a fasting-mimicking diet promotes long-lasting tumour regression and reverts acquired resistance to drug treatment. Moreover, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia. In patients with hormone-receptor-positive breast cancer receiving oestrogen therapy, cycles of a fasting-mimicking diet cause metabolic changes analogous to those observed in mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity. These results support further clinical studies of a fasting-mimicking diet as an adjuvant to oestrogen therapy in hormone-receptor-positive breast cancer.

Effects of the Postoepartive Dietetic/Behavioral Counseling on the Weight Loss After Bariatric Surgery.

OBJECTIVE: Weight outcomes after bariatric surgery are due to an adequate adjustment of eating behavior to the new gastrointestinal conditions created by operation. The efficacy of dietary/behavior counseling for promoting weight loss and maintenance in a growing number of bariatric patients was investigated. MATERIAL AND METHODS: One hundred seventy-six non-diabetic obese patients undergoing Roux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG) were investigated. The first group (CO, 88 subjects, 16 male) attended a standard surgical follow-up, while in the second (DIET, 88 subjects, 15 male) the surgeon was supported by a dietitian, and patients received behavioral-dietary sessions on individual request. Data prior to the operation and at 2 years were considered, the weight outcome being regarded as successful when postoperative body mass index (BMI) value was lower than 30 kg/m2. RESULTS: Weight results were better (p < 0.01) in the RYGBP than in the SG patients. In comparison to CO, in the DIET group a greater adherence to the bariatric program was observed (76% vs. 41%, < 0.01), while body weight data and prevalence of successful cases at 2 years (87 ± 23 vs. 83 ± 16 kg and 27% vs.33%, respectively) were similar. CONCLUSIONS: After RYSG and SG, postoperative dietetic/behavioral sessions delivered on patient's request does not influence weight results. The dietetic intervention promotes the adherence to bariatric program and prevents postoperative follow-up loss. In a dietitian/behavioral strategy after RYGBP and SG, a cognitive reinforcement of the compliance to bariatric program and a strengthening of the motivation to changes could promote better weight results.

Disordered eating and weight loss after bariatric surgery.

PURPOSES: Aberrant eating patterns are frequently observed in bariatric patients. Since bariatric operations produce alterations in food transit and in appetite/satiety balance, postoperative eating behavior changes are not surprising. METHODS: 88 consecutive obese patients undergoing Roux-en-Y gastric bypass (RYGBP, 50 cases) and Sleeve Gastrectomy (SG, 38 cases) were retrospectively evaluated. Beside anthropometric data measurement, eating behavior was assessed by direct interview prior to the operation and at the first and second postoperative years: patients were considered as eating disordered (ED) when referred habitual occurrence of binge eating and nibbling/grazing. Weight loss was assessed by percent of BMI loss (% Δ BMI). Together with standard follow-up, patients received additional behavioral/dietetic support upon request. RESULTS: Postoperative ED patients showed lower % Δ BMI than the not ED ones at one (30.7% ± 8,5 vs. 26.8% ± 10, p < 0.02) and two (32% ± 10.3 vs. 27.4% ± 12.9, p < 0.05) years after operation, the follow-up rate being 82% and 76%, respectively, without differences between RYGBP and SG group. After RYGBP, an improvement of eating behavior was observed (ED patients from 75 to 28% at 1 year and to 27% at 2 years), while no changes were observed after SG. In SG patients, the number of additional behavioral/dietetic support sessions throughout the follow-up was positively associated with % Δ BMI. DISCUSSION: The postoperative normalization of eating pattern has a role in weight loss after bariatric surgery. Behavioral/dietetic support is indicated in all SG patient, while after RYGBP is useful only when weight loss is unsatisfactory. LEVEL OF EVIDENCE: III: retrospective cohort study.

The predictive dysphagia score (PreDyScore) in the short- and medium-term post-stroke: a putative tool in PEG indication.

PURPOSE: We performed an evaluation of dysphagia in an unselected series of strokes to identify factors causing persisting dysphagia at 1 month after onset and to formulate a predictive score. METHODS: We evaluated the association between dysphagia and clinical aspects (univariate analysis) at the 7th and 30th days after admission. We performed a multivariate logistic regression at the 30th day on the factors that were significant. We computed a simple score for predicting persistent dysphagia. RESULTS: We recruited 249 patients. At the 7th day, 94 patients were dysphagic (37.75%). Factors associated with dysphagia included TACI (OR 3.85), mRS ≥ 3 (OR 4.45), malnutrition (OR 2.69), and BMI ≥ 20 (OR 0.52). At the 30th day, 217 patients remained in the study, and dysphagia persisted in 75 (36.76%). The factors that were associated with dysphagia were age > 74 years (OR 1.99), TACI (OR 5.82), mRS score ≥ 3 (OR 4.31), malnutrition (OR 3.27), and BMI ≥ 20 (OR 0.45). The multivariate analysis indicated that mRS ≥ 3 (OR 1.80) and BMI ≥ 20 (OR 0.45) remained significantly associated with dysphagia. The best correlation with dysphagia was the sum of mRS and the reciprocal of the BMI multiplied by 100 ((mRS + 1 ∕ BMI) × 100). We named this score PreDyScore that ranged between 3.7 and 10.47. Using < 6 and > 8 as cutoffs, the sensitivity was 67.03%, and the specificity 95.65%. CONCLUSION: BMI < 20 and mRS ≥ 3 are easily measurable bedside predictive factors of persistent dysphagia. PreDyScore showed good sensitivity and very good specificity and enables the prediction of persistent dysphagia with great accuracy in any clinical setting.

Serum Leptin and Adiponectin Concentration in Type 2 Diabetes Patients in the Short and Long Term Following Biliopancreatic Diversion.

BACKGROUND: A deranged adipokine system is implicated in obesity and in type 2 diabetes mellitus (T2DM), and the lack of remission of T2DM after bariatric surgery could be also accounted for by the postoperative persistence of this condition. METHODS: Thirty T2DM patients undergoing biliopancreatic diversion (BPD) with a wide range of baseline body mass index (BMI) were evaluated prior to and at 1 and 5 years following BPD. Besides the usual clinical evaluations, acute insulin response (AIR) to intravenous glucose load as a parameter of insulin secretion and the serum leptin and adiponectin concentration were measured throughout the follow-up period in all patients. RESULTS: A long-term T2DM remission was observed in 21 patients (70 %). Serum leptin level reduced at the first year and remained substantially unchanged at a long term in both the remitter and non-remitter patients, while following the operation, a progressive significant increase of serum adiponectin level was observed only in remitter patients (from 9.2 to 12.3 µg/mL at 1 year and to 15.18 µg/mL at 5 years in the remitters and from 8.8 to 8.75 µg/mL at 1 year and to 11.8 µg/mL at 5 years in the non-remitters). Serum leptin mean values were positively associated with the BMI ones both prior to and following BPD (p < 0.005), while serum adiponectin values were positively related (p < 0.04) to the postoperative AIR data. CONCLUSIONS: The improvement of the pattern of cytokine production, as evidenced by postoperative rise in serum adiponectin concentration, might play a role in T2DM remission after bariatric surgery.

Physical activity after surgically obtained weight loss: study with a SenseWear armband in subjects undergoing biliopancreatic diversion.

BACKGROUND: This study aimed to understand the role of the extra load of body mass in limiting physical activity and in preventing an active lifestyle in severely obese patients. MATERIALS AND METHODS: The study was carried out in a University Hospital setting, and investigates severely obese patients, having undergone biliopancreatic diversion (BPD) for obesity and control subjects with a body weight closely similar to that of the BPD subjects; energy intake was evaluated by alimentary interview and energy expenditure was assessed with the Body Media SenseWear® Pro armband (SWA). RESULTS: SWA metabolic efficiency (MET) was negatively associated with body mass index values (ρ = -0.464, p < 0.01), and the SWA overall energy expenditure was very similar to the energy alimentary intake in the obese patients and in the control subjects. Among the controls, the MET mean value was higher (p < 0.05) than that observed both in obese and in BPD subjects (1.392 ± 0.211 vs. 1.149 ± 0.181 and 1.252 ± 0.284, respectively); furthermore, in comparison with the obese and the BPD groups, among the control individuals a greater number of active persons (27% vs. 0 and 7%, respectively) and a lower number of sedentary persons (27% vs. 70 and 43%, respectively) was found (p < 0.01). CONCLUSIONS: These preliminary results suggest the reliability of SWA data in assessing energy expenditure and tend to rule out the hypothesis that in severely obese patients the extra load of body mass by itself is a main factor limiting physical activity and leading to a sedentary lifestyle.

Appetite control and gastrointestinal hormonal behavior (CCK, GLP-1, PYY 1-36) following low doses of a whey protein-rich nutraceutic.

Whey proteins represent the most satiating nutrients. In particular, their effects are due to enterohormonal changes (CCK, GLP-1 and PYY 1-36) observed after their exclusive ingestion. Glucomannan has important satiety property due to volume increase following gelification. The aim of the study is the evaluation of subjective rate of hunger and enterohormone concentrations (CCK, GLP-1, PYY 1-36) following oral loading of a mixture containing WP (8 g) or casein (8 g) plus glucomannan (1 g) (Colordiet®, Inpha DUEMILA Srl Lecco, Italy). The study was conducted as a double-blind crossover with five healthy volunteers (BMI 22-26 kg/m2 aging 18-65 years) in acute and a wash-out period of 1 week between the first and the second evaluation. From the analysis of the data, we observe that the load with WP induces a significant decrease in the desire to eat after 90 min (P < 0.0446) when compared with casein. As far as plasma hormones are concerned, there was a significant increase only in GLP-1 at 90 min after WP (P < 0.00166) and 180 min after casein (T0 vs. T180 P = 0.000129). There is a significant correlation between the increase in GLP-1 and decrease of desire to eat (R = -0.93). There is a tendency to the increasing of CCK after 90 min, which is not significant (P = 0.091). These results could be due to (a) the low number of cases or (b) the low dose of protein used. The present study suggests that a mixture of WP plus glucomannan exerts a decrease in the desire to eat which is correlated to enterohormonal modification (GLP-1 increase) despite the low content of protein (8 g) and the presence of glucomannan, which could reduce the fast absorption of WP in relation to the net forming during the gelification of the gastric environment.

Body weight at developmental age in siblings born to mothers before and after surgically induced weight loss.

BACKGROUND: To gain insight into the role of epigenetic factors in determining body weight in adolescence, we studied the body weight of siblings born to the same mother before and after biliopancreatic diversion (BPD) for obesity. The study was performed in a university hospital during a 20-year period. METHODS: The siblings born before and after BPD were retrospectively rated by their mother as normal, overweight, or obese at 1, 6, and 12 years. RESULTS: At 1 and 6 years, the body weight was rated as similar in the subsets. However, at 12 years of age, a greater percentage of those born before BPD were considered overweight (42% versus 33%) and obese (22% versus 3%; P <.009) than their counterparts born after BPD. Considering only the subjects aged 21-25 years at the study period, the body weight and body mass index in subjects born before BPD were greater (P <.02 and P <.012, respectively) than in those born after BPD (79.5 ± 16.5 kg versus 66.7 ± 11.8 kg, and 27.5 ± 3.9 kg/m(2) versus 23.4 ± 3.7 kg/m(2), respectively). CONCLUSION: The results of the present study, in which the influences of the genetic pattern and environmental and educational factors were minimized, show that adolescents born to post-BPD mothers weigh less than their siblings born to the same mother before BPD when she was still obese. An insulin-resistant milieu during pregnancy could account for the greater body weight later in adolescence.