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Aims: Long-term clinical trials evaluating the effects of metabolic-bariatric surgery (MBS) on type 2 diabetes (T2D) demonstrate that a significant proportion of patients either fail to achieve remission or experience T2D recurrence over time. Furthermore, patients with recurrent T2D might require reinstitution of pharmacotherapy to control comorbidities (hypertension, dyslipidemia). This paper reviews therapeutic options in patients with T2D relapse. Data synthesis: Although presently there is no recommended pharmacological strategy, the available data support GLP-1 analogues (GLP-1a) as the most suitable option to control hyperglycemia post-MBS. Beside their efficacy in lowering glycemia and body weight while preserving lean mass, GLP-1a exert cardiovascular/renal-protection and are also safe and well tolerated in surgical patients. In addition, the s.c. route of administration of these medications circumvents the problem of changes in oral drugs bioavailability following MBS. Of note, the available data refers to liraglutide and needs to be confirmed with weekly GLP-1a agents. Information regarding the impact of MBS on the pharmacokinetics of lipid lowering and anti-hypertensive drugs is scarce and inconclusive. The findings indicate that timing from intervention is particularly important because of adaptive intestinal mechanisms. Conclusions: The recurrence of T2D following MBS is a clinically relevant issue. GLP-1a therapy represents the best option to improve glycemic and weight control with good tolerability. Long-term clinical trials will clarify the impact of these drugs on cardiovascular outcomes. A close monitoring of MBS patients is advised to guide drug dosage adjustments and ensure the control of cardiovascular risk factors.

Obstructive sleep apnea syndrome (OSAS) and obesity are frequently associated with hypertension (HTN), dyslipidemia (DLP), and insulin resistance (IR). In patients with obesity and OSAS scheduled for bariatric surgery (BS), guidelines recommend at least 4 weeks of preoperative continuous positive airway pressure (CPAP). Low-calorie ketogenic diets (LCKDs) promote pre-BS weight loss (WL) and improve HTN, DLP, and IR. However, it is unclear whether pre-BS LCKD with CPAP improves OSAS more than CPAP alone. We assessed the clinical advantage of pre-BS CPAP and LCKD in patients with obesity and OSAS. Seventy patients with obesity and OSAS were randomly assigned to CPAP or CPAP+LCKD groups for 4 weeks. The effect of each intervention on the apnea–hypopnea index (AHI) was the primary endpoint. WL, C-reactive protein (CRP) levels, HTN, DLP, and IR were secondary endpoints. AHI scores improved significantly in both groups (CPAP, p=0.0231; CPAP+LCKD, p=0.0272). However, combining CPAP and LCKD registered no advantage on the AHI score (p=0.863). Furthermore, body weight, CRP levels, and systolic/diastolic blood pressure were significantly reduced in the CPAP+LCKD group after 4 weeks (p=0.0052, p=0.0161, p=0.0008, and p=0.0007 vs baseline, respectively), and CPAP+LCKD had a greater impact on CRP levels than CPAP alone (p=0.0329). The CPAP+LCKD group also registered a significant reduction in serum cholesterol, LDL, and triglyceride levels (p=0.0183, p=0.0198, and p

Background: Roux-en-Y gastric bypass (RYGB) is currently one of the most performed bariatric procedures and it is associated with rapid weight loss. However, weight loss failure and weight regain after RYGB occurs in approximately 30% and 3–5% of patients, respectively, and represent a serious issue. RYGB pouch resizing is a surgical option that may be offered to selected patients with RYGB failure. The aim of this study is to assess long-term results of pouch resizing for RYGB failure. Materials and Methods: From February 2009 to November 2011, 20 consecutive patients underwent gastric pouch resizing for RYGB failure in our tertiary bariatric center. The primary outcome was the rate of failure (%EWL < 50% with at least one metabolic comorbidity) after at least 10 years from pouch resizing. Gastroesophageal Reflux Disease (GERD) was also assessed. Results: Twenty patients (18 women (90%)) were included and seventeen (85%) joined the study. The failure rate of pouch resizing was 47%. Mean %EWL and mean BMI were 47%, and 35.1 kg/m2, respectively. Some of the persistent co-morbidities further improved or resolved after pouch resizing. Seven patients (41%) presented GERD requiring daily PPI with a significantly lower GERD-HQRL questionnaire score after pouch resizing (p < 0.001). Conclusion: Pouch resizing after RYGB results in a failure rate of 47% at the 10-year follow-up while the resolution of comorbidities is maintained over time despite a significant weight regain.

Longevity is rightly considered one of the greatest achievements of modern society. Biomedical research has shown that aging is the major risk factor for many diseases, so to find the right answers to aging it is necessary to identify factors that can positively influence longevity. This study investigated the clinical status, nutritional behavior, lifestyle, and social and community determinants of the well-being of young older adults and nonagenarians/centenarians in Salerno and province through the judgment of their physicians. Data were collected through an online survey. Multivariate Poisson and logistic regression models were used to calculate significant predictors of the outcomes of interest. The interesting finding was that cardiovascular disease was a risk factor for young older adults, while it was a protective factor for nonagenarians/centenarians, meaning that as age increased, heart problems tended to decrease. Certain foods were found to be a significant protective factor for both young older adult and nonagenarian–centenarian patients. In addition, psychosomatic disorders were found to be determinant for the young older adults, while depression was a risk factor for the nonagenarians/centenarians because they were not always gratified by their long lives and often felt like a burden on the family. The protective significant variable among the determinants of community well-being for both young older adults and nonagenarians/centenarians was the retention of honorary achievement. Based on our results, we are able to support the hypothesis of a difference between the young older adults and the nonagenarians/centenarians in clinical status, nutritional behaviors, lifestyle, and determinants of community well-being. However, societies need more social and educational programs that are able to build “a new idea of old age” by improving and supporting the young older adults and the nonagenarians/centenarians, with the goal of intergenerational solidarity, well-being, and social inclusion, as well as preventive interventions on lifestyles and nutrition, which will allow us to provide a new key to understanding aging.

Objectives: To evaluate the effect of the SARS-CoV-2 lockdown on dietary habits, body weight, left hepatic lobe volume, use of micronutrient supplements, micronutrient status, frequency of physical activity, and evolution of comorbidities in patients undergoing preoperative care for BS. Materials and Methods: We prospectively evaluated the dietary habits (including use of micronutrient supplements and frequency of physical activity) of 36 patients who were candidates for BS from March to May 2020; 7-day food dietary records, body weight, left hepatic lobe volume by ultrasound, micronutrient status, and evolution of comorbidities were assessed. Results: All patients completed the study. Of the participants, 44.4% (16/36), 47.2% (17/36), and 27.8% (10/36) followed the preoperative indications for vegetables, fruits, and legumes, respectively, whereas over 50% did not. Furthermore, 30.6% (11/36) and 55.6% (20/36) of participants followed the prescribed recommendations for carbohydrates/sweets products and alcohol, respectively. A total of 61.1% (22/36) of participants experienced new foods and new culinary preparations. In addition, at the time of the study, we found that only 11.1% (4/36) were engaged in prescribed physical activity and only 36.1% (13/36) were taking prescribed micronutrient supplements. Compared to the initial weight, we observed an increased body weight and body mass index (+4.9%, p = 0.115; +1.89%, p = 0.0692, respectively), and no improvement in left hepatic lobe volume, micronutrient status, or comorbidities was recorded for any patient in the anamnesis. Conclusions: Lockdown determined by the SARS-CoV-2 pandemic has negatively affected the preoperative program of BS candidates, resulting in a postponement to the resumption of bariatric surgical activity.

Background: Hypoparathyroidism-related hypocalcemia is a common complication after total thyroidectomy (TT), particularly if there is a history of prior bariatric surgery. However, it is still unknown if it is the surgery timing or the type of bariatric intervention that increases the risk of developing this complication. Methods: We compared the risk of hypocalcemia (serum calcium levels < 8 mg/dL) and hypoparathyroidism (both transient and permanent) between patients with restrictive procedures (LSG and GB) and patients without a history of obesity surgery in the immediate post-operative period and after 12 months. Hypoparathyroidism was considered permanent if the plasma parathyroid hormone (PTH) levels at 6 months were less than 15 pg/mL and the patient still required oral calcium (calcium carbonate) and vitamin D supplementation, in addition to the supplements that were taken routinely before thyroidectomy. Results: From the 96 patients who underwent TT, 50% had a history of bariatric surgery: 36 LSG and 12 GB. The risk of hypocalcemia was similar in patients with a history of restrictive procedures (31.35%) and in controls (25%) (p = 0.49). Furthermore, hypocalcemia risk was similar between patients with a history of LSG (30.5%) and GB (33%) (p = 0.85). The prevalences of transient and permanent hypoparathyroidism were similar between patients with a history of restrictive procedures and in controls; similarly, no differences were detected between subjects undergoing LSG and GB. Conclusions: Restrictive bariatric surgery (LSG and GB) is not a risk factor for post-thyroidectomy hypocalcemia and hypoparathyroidism and thus did not require a different perioperative supplementation protocol compared to subjects without history of bariatric surgery undergoing TT.

Aims: Hypoglycemia is a serious complication of bariatric surgery. The aim of the present meta-analysis was to evaluate the rate and the timing of post-bariatric hypoglycemia (PBH) with different bariatric procedures using reliable data from continuous glucose monitoring (CGM). Data synthesis: Studies were systematically searched in the Web of Science, Scopus and PubMed databases according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of PBH was expressed as weighted mean prevalence (WMP) with pertinent 95% confidence intervals (95%CI). A total of 8 studies (16 datasets) enrolling 280 bariatric subjects were identified. The total WMP of PBH was 54.3% (95%CI: 44.5%–63.8%) while the WMP of nocturnal PBH was 16.4% (95%CI: 7.0%–34%). We found a comparable rate of PBH after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) (OR 1.62, 95%CI: 0.71–3.7; P = 0.248); likewise, the percent time spent in hypoglycemia was similar with the two procedures (mean difference 5.3%, 95%CI: −1.4%–12.0%; P = 0.122); however, RYGB was characterized by a higher glycemic variability than SG. Regression models showed that the time elapsed from surgical intervention was positively associated with a higher rate of both total PBH (Z-value: 3.32, P < 0.001) and nocturnal PBH (Z-value: 2.15, P = 0.013). Conclusions: PBH, both post-prandial and nocturnal, is more prevalent than currently believed. The rate of PBH increases at increasing time from surgery and is comparable after RYGB and SG with a higher glucose variability after RYGB.

International audience; BACKGROUND: Liver steatosis in morbidly obese individuals undergoing bariatric surgery increases liver volume and may complicate the surgical procedure. This study aimed to assess whether a 4-week supplementation with omega-3 polyunsaturated fatty acids (PUFA) is effective in reducing liver left lateral section (LLLS) volume. PATIENTS AND METHODS: This randomized controlled trial included morbidly obese individuals with metabolic syndrome undergoing bariatric surgery at 3 French bariatric centers between 2017 and 2020. The experimental group had a 4-week preoperative supplementation with omega-3 PUFA, whereas the control group had only placebo. The primary outcome was the reduction of the LLLS volume measured with Magnetic Resonance Imaging (MRI). RESULTS: 42 patients were randomized and 37 completed the study (19 in the experimental group and 18 in the placebo group). The mean LLLS volume decreased of 3.3% (±9.6) in the experimental group vs 1.0% (±18.3) in the placebo group, indicating that omega-3 PUFA were not effective in reducing the LLLS volume compared to the placebo (p = 0.3741). Omega-3 PUFA supplementation was not effective in reducing total liver volume, liver steatosis, rate of liver injuries during surgery and operative time. CONCLUSION: A 4-week preoperative supplementation with omega-3 PUFA was not effective in reducing LLLS volume in morbidly obese individuals undergoing bariatric surgery.

Longevity is rightly considered one of the greatest achievements of modern society, an achievement understood as the possibility of increasing the healthy part of life and not only its full duration. This study investigated the phenomenon of regional longevity in Cilento by analyzing the association between longevity indicators and some environmental factors, in order to understand if factors such as altitude, climate, UNESCO protected areas, and hinterland can directly or indirectly influence the measure of healthy living and lead to longevity. Demographic and environmental data were collected through the Archives of the Cilento municipalities, the National Institute of Statistics, the Italian Institute for Environmental Protection and Research, and the Italian National Commission for UNESCO. The Geographically Weighted Regression were used to determine the association between longevity indicators and environmental factors. Correlation analysis between the longevity indicators was investigated in order to have a complete picture of longevity in Cilento. It was discovered that Cilento longevity is mainly found in the central area of the territory and from there, by age groups, it widens towards the south-eastern area. This designated area is part of the hilly area of the Cilento, at an altitude between 400 and 700 m above sea level. The towns of this area are part of the UNESCO heritage and are characterized by a transitional climate between Mediterranean and temperate climate. Moreover, the correlation analysis between the six indicators of longevity has confirmed a linear relationship between the six variables and this indicates that in the years to come there will be the probabilities of a generational turn over between the old, great old, nonagenarians and current centenarians, provided that the SARS-CoV-2 pandemic subsides.

The link between obesity epidemic in fertile age and fertility reduction, in relation with BMI increase, has been demonstrated. An inverse proportionality between BMI and anti-Müller hormone (AMH) has been investigated. This hormone is strictly related to ovarian function. It has been demonstrated that it is significantly decreased in obese women.The aim of this study was evaluation of AMH levels in 53 obesity women with BMI35, at 3 and 6 months after laparoscopic sleeve gastrectomy (LSG). Specific evaluation of comorbidities and of gynecological effects of weight loss was also evaluated.Cohort of 53 women was considered, treated with LSG. A progressive increase of AMH levels after LSG was confirmed, with statistically significant results at followup of 6 months. In these patients, we also observed an improvement in the menstrual cycle and resolution of dysmenorrhea. All considered comorbidities were ameliorated at both followup.LSG determined a significant increase of AMH level in women, at early followup, with a comprehensive amelioration of gynecological status. Larger cohorts and a better evaluation of ovarian function after LSG will lead to more powerful results of the effect of weight loss on women.

Obesity is a well-recognized global health problem, and bariatric surgery (BS)-induced weight reduction has been demonstrated to improve survival and obesity-related conditions. Sleeve gastrectomy (SG) is actually one of the most performed bariatric procedures. The underlying mechanisms of weight loss and its maintenance after SG are not yet fully understood. However, changes to the taste function could be a contributing factor. Data on the extent of the phenomenon are limited. The primary objective was to assess, through validated questionnaires, the percentage of patients who report an altered perception of post-SG taste and compare the frequency of intake of the different food classes before SG and after 1 year follow-up. The secondary objective was to evaluate the total body weight change. Materials and Methods: We prospectively investigated the changes in food choice and gustatory sensitivity of 52 patients (55.8% females) 12 months after SG. The mean initial weight and body mass index (BMI) were 130.9 ± 24.7 kg and 47.4 ± 7.1 kg/m2, respectively. The frequency of food intake was assessed by food-frequency questionnaire, while changes in taste perception were assessed using the taste desire and enjoyment change questionnaire. The change in total body weight was also assessed. Results: A significant decrease in the intake frequency of bread and crackers (p < 0.001), dairy products and fats (p < 0.001), sweets and snacks (p < 0.001) and soft drinks (p < 0.001), and a significant increase in the frequency of vegetable and fruit consumption (p < 0.001) were observed at 12 months after SG in both genders. On the contrary, we found no significant changes in the frequency of meat and fish intake in females (p = 0.204), whereas a significant change was found in males (p = 0.028). Changes in perceived taste intensity of fatty foods (p = 0.021) and tart foods (p = 0.006) for females and taste of bitter foods for females and males (p = 0.002; p = 0.017) were found. Regarding the change in food desire for both genders, there was a decrease in the desire for sweet, fatty, and salty foods, whereas there was an increasing trend in the desire for tart foods, especially for females. Significant reduction in total body weight and BMI was observed in both genders at the time of follow-up. Conclusions: Based on our findings, we are able to support the evidence that changes in taste, desire, and enjoyment of taste are very common after SG, with a reduced preference for food with high sugar and fat content and an increased postoperative preference for low-sugar and -fat foods. However, further investigation is needed to clarify this issue. The molecular, hormonal, and central mechanisms underlying these changes in taste perception need to be further elucidated, as they could identify new targets able to modify obesogenic eating behavior, opening up a novel personalized therapeutic approach to obesity.

Background and aims: Although the use of Continuous Glucose Monitoring (CGM) is rapidly extending, little evidence is currently available on daily glycemic excursions after different bariatric procedures. We assessed glycemic patterns after sleeve gastrectomy (SG) and roux-en-Y gastric bypass (RYGB) using CGM. Methods and results: Cross-sectional study in subjects who had undergone RYGB (n = 22) or SG (n = 29) since at least 1 year, without pre-surgery or in current diabetes (T2DM) remission. All subjects underwent 7 day-CGM (Dexcom G4 PLATINUM), which provides glucose variability (GV), number and time spent in hypoglycemia, hypoglycemia patterns (postprandial, nocturnal or mixed). All indexes of GV were higher after RYGB than after SG (p < 0.001). Twenty-eight (55%) subjects experienced hypoglycemia. The number of events was higher after RYGB than SG (p = 0.017) while it did not differ in subjects with or without pre-surgery T2DM (p = 0.129). Overall, 9 (32%) subjects presented hypoglycemia exclusively during the postprandial period, 8 (29%) an exclusively nocturnal pattern and 11 (39%) a mixed pattern. The nocturnal pattern was more frequent after SG than RYGB (53.8% vs 6.7%, p = 0.036) while no difference was observed in subjects with or without pre-surgery T2DM (p = 0.697). Hypoglycemia symptoms were more frequent in subjects with postprandial than in those with nocturnal pattern (77.8% vs 12.5%, p = 0.015). Conclusions: RYGB is characterized by a greater GV and a higher number of hypoglycemia events mostly post-prandial and symptomatic, while SG is associated with nocturnal and often asymptomatic hypoglycemia. These findings suggest that post-bariatric hypoglycemia is a more complex, not exclusively, postprandial phenomenon.

To assess dietary habits in a cohort of patients at minimum follow-up of 4 years after sleeve gastrectomy (SG) by comparing their dietary records to the Italian Mediterranean diet (IMD) recommendations. We prospectively evaluated in 74 patients who had the SG in 2014 dietary habits by a 7-day food dietary records, weight and micronutrient status, evolution of comorbidities, use of micronutrient supplements, and frequency of physical activity. The IMD recommendations in terms of daily/weekly portions of fruits, vegetables, and complex carbohydrates were followed by 40.5%, 35.1%, and 40.5% of the participants, respectively. Concerning milk/dairy, olive oil, poultry, fish/shellfish, eggs, legumes, processed/red meat, and cold cuts, 54.1%, 85.1%, 44.5%, 75.7%, 67.6%, 35.1%, 87.8%, and 55.4% of the participants, respectively, followed the IMD recommendations. Weight regain appeared in 37.8% of participants, while physical activity was reported by the 54.0% of them. Deficiencies of vitamin B12, vitamin D, folate, iron, and anemia were found present in 6.8%, 8.1%, 24.3%, 33.8%, and 59.5% of the participants, respectively, and 18.9% of them were found to take micronutrient supplements. Improvement/remission of type 2 diabetes, hypertension, or obstructive sleep apnea was 73.3%, 64.7%, and 100% respectively. In this prospective cohort with a minimum follow-up of 4 years after SG, we found an inadequate intake of fruit, vegetables, poultry, and complex carbohydrates according to the IMD recommendations; the frequency of physical activity and the use of micronutrients supplements were also inadequate. This may contribute to weight regain and micronutrient deficiencies in the long term.

Background The Elipse™ intragastric balloon (EIGB) is a new swallowable balloon for weight loss (WL). Preserving metabolically active fat-free mass (FFM) and resting metabolic rate (RMR) during WL are crucial to maximize fat mass (FM) loss. After EIGB placement, a standard low-calorie diet (LCD) is generally prescribed. A low-calorie ketogenic diet (LCKD) has proven to be safe and effective in reducing FM while preserving FFM and RMR. Objective To prospectively compare the effects on WL, FM, FFM, and RMR in two groups of patients who were randomized to two different diets: LCKD and a standard LCD after EIGB placement. Methods WL, FM, FFM, and RMR were measured before EIGB and at 4 months in 48 patients who received either a LCKD (n = 24) or a standard LCD (n = 24). Compliance in following the prescribed diet was determined with food frequency questionnaires in all patients. The impact of LCKD and LCD on renal function was also evaluated. Results The LCKD group showed a significantly lower decrease in FFM and RMR when compared with the LCD group (3.55 vs 14.3%, p p p = 0.0606). Compliance in following the prescribed diets, without negative impact on renal function, was found. Conclusion Based on our findings, despite the small sample size, we were able to support the hypothesis that LCKD is associated with an increased FM loss while reducing the FFM loss and the RMR, without interfering with renal function after EIGB.

Abstract. We aim to assess the prevalence of vitamin D deficiency (VDD) in patients scheduled for bariatric surgery (BS), and to identify factors that might be associated with VDD. We conducted a cross-sectional observational study involving all consecutive patients scheduled for BS from 2017 to 2019. The exclusion criteria were missing data for vitamin D levels, intake of vitamin D supplements in the 3 months prior to serum vitamin D determination, and renal insufficiency. A total of 206 patients (mean age and body mass index [BMI] of 34.9 ± 10.7 years, and 44.3 ± 6.99 kg/m2, respectively) met the inclusion criteria and were enrolled for data analysis. VDD (

Background Previous studies have demonstrated significant advantages from a preoperative dietetic regimen for candidates to bariatric procedure. Objectives Evaluation of safety, efficacy, and acceptability of a very low-calorie ketogenic diet in patients before bariatric surgery. Setting University Hospital. Methods A standardized 30-day sequential preoperative diet regimen has been analyzed, optimizing metabolic response with gradual carbohydrate reintroduction. Patients were given a dedicated KetoStationkit, for use during the first 10 days of the scheme, followed by a hypocaloric scheme for 20 days. The study group underwent routine laboratory tests and anthropometric measurements (percent weight loss, body mass index, waist circumference) at enrollment (T0), after 10 days (T1), and after 30 days (T2). Ketone body levels were measured in the plasma and urine. Results Between January 2015 and September 2015, 119 patients were included in the study. Mean body mass index was 41.5 ± 7.6 kg/m2. Weight, body mass index, and waist circumference at T0 and T1, T0 and T2, and T1 and T2 decreased significantly (P Conclusion Our results confirm the acceptability, safety, and significant advantage of a very low-calorie ketogenic diet for reducing weight and liver volume of patients in preparation for bariatric surgery.

Glioblastoma multiforme is the most common and aggressive primary brain cancer with only ∼3% of patients surviving more than 3 years from diagnosis. Several mechanisms are involved in drug and radiation resistance to anticancer treatments and among them one of the most important factors is the tumor microenvironment status, characterized by cancer cell hypersecretion of interleukins and cytokines. The aim of our research was the synthesis of a nanocarrier of quercetin combined with temozolomide, to enhance the specificity and efficacy of this anticancer drug commonly used in glioblastoma treatment. The nanohydrogel increased the internalization and cytotoxicity of quercetin in human glioblastoma cells and, when co-delivered with temozolomide, contribute to an improved anticancer effect. The nanohydrogel loaded with quercetin had the ability to recognize CD44 receptor, a brain cancer cell marker, through an energy and caveolae dependent mechanism of internalization. Moreover, nanohydrogel of quercetin was able to reduce significantly IL-8, IL-6, and VEGF production in pro-inflammatory conditions with interesting implications on the mechanism of glioblastoma cells drug resistance. In summary, novel CD44 targeted polymeric based nanocarriers appear to be proficient in mediating site-specific delivery of quercetin via CD44 receptor in glioblastoma cells. This targeted therapy lead to an improved therapeutic efficacy of temozolomide by modulating the brain tumor microenvironment. Glioblastoma multiforme is the most common and aggressive primary brain cancer with only approximate to 3% of patients surviving more than 3 years from diagnosis. Several mechanisms are involved in drug and radiation resistance to anticancer treatments and among them one of the most important factors is the tumor microenvironment status, characterized by cancer cell hypersecretion of interleukins and cytokines. The aim of our research was the synthesis of a nanocarrier of quercetin combined with temozolomide, to enhance the specificity and efficacy of this anticancer drug commonly used in glioblastoma treatment. The nanohydrogel increased the internalization and cytotoxicity of quercetin in human glioblastoma cells and, when co-delivered with temozolomide, contribute to an improved anticancer effect. The nanohydrogel loaded with quercetin had the ability to recognize CD44 receptor, a brain cancer cell marker, through an energy and caveolae dependent mechanism of internalization. Moreover, nanohydrogel of quercetin was able to reduce significantly IL-8, IL-6, and VEGF production in pro-inflammatory conditions with interesting implications on the mechanism of glioblastoma cells drug resistance. In summary, novel CD44 targeted polymeric based nanocarriers appear to be proficient in mediating site-specific delivery of quercetin via CD44 receptor in glioblastoma cells. This targeted therapy lead to an improved therapeutic efficacy of temozolomide by modulating the brain tumor microenvironment.

Bariatric surgery (BS) has grown exponentially in France, and long-term anemia due to micronutrient deficiencies has become common. The objective of this study was to assess the long-term risk of anemia after BS and to investigate the factors associated with the occurrence of this complication. Data from the French National Health Service database on patients who had undergone gastric bypass (GB), sleeve gastrectomy (SG), or adjustable gastric banding (AGB), between 2008 and 2016 were extracted. Only patients with a primary intervention were considered. Data from 306,298 patients (143.733 SG, 79.188 GB, and 36.413 AGB) were analyzed. Overall, 12.930 of them (5.0%) had a diagnosis of anemia due to micronutrient deficiencies as main diagnosis or related diagnosis at time of a hospital stay between 2008 and 2016. In multivariate analysis, GB surgery, female gender, age younger than 52 years, and 25-OH vitamin D deficiency were positively associated with the occurrence of anemia whereas hospital procedural volume was negatively associated. The risk to be diagnosed with anemia after BS was 13.0% after a GB, 5.6% after a SG and 4.0% after an AGB (Log-rank p

Abstract. Micronutrient deficiencies (MD) shortly after sleeve gastrectomy (SG) are frequent and patients with obesity often show MD preoperatively. Our aim was to assess whether the correction of MD before SG could play a role in preventing early postoperative MD. Eighty patients (58 females, 22 males) who underwent SG were evaluated retrospectively. Patients were divided according to whether they had received preoperative MD correction (Group A, n = 42; 30 females, 12 males) or not (Group B, n = 38; 28 females, 10 males). Micronutrient status was assessed preoperatively, at 3 and 12-months after SG in both groups. After SG, Group A and Group B patients received the same multivitamin supplement and followed the same diet. Nutrient intake of all patients was evaluated by food frequency questionnaires. Before SG, patients of Group A had no MD, whereas patients of Group B were mostly deficient in vitamin B12 (10.5%, 3 women, 1 man), folate (15.8%, 5 women, 1 man), 25-vitamin D (39.5%, 10 women, 5 men), iron (26.3%, 8 women, 2 men), and zinc (7.9%, 2 women, 1 men). At 3- and 12-month follow-up, no patient in group A had developed new MD, whereas all patients of Group B continued to be deficient in one or more micronutrient, despite systematic postoperative supplementation. No statistical differences (p

The impact of bariatric surgery (BS) on the sexual functioning of patients is poorly studied. Our aim was to analyze the sexual function, depressive symptoms, and self-esteem of morbidly obese women (MOW) undergoing BS. Quality of sexual life was prospectively evaluated in 43 consecutive MOW (18–50 years) who underwent BS. Female sexual function index (FSFI), Beck depression inventory (BDI), and Rosenberg self-esteem scale (RSES) questionnaires were administered to evaluate sexual satisfaction, depressive symptoms, and self-esteem, respectively. A control group of 36 healthy, non-obese, female patients (HW) was recruited for comparison. Results of questionnaires were compared between three periods (before BS and at 3- and 6-month follow-up) and between MOW and HW. Before BS, the FSFI score was significantly lower in MOW compared to HW (17 ± 12 vs 27 ± 8, p = 0.0001) while at 3- and 6-month post-BS, a significant amelioration (p = 0.01) occurred. In particular, after BS, all components of the FSFI score (sexual desire, excitement, lubrification, orgasm, satisfaction, and pain) were ameliorated. The pre-BS BDI score was higher in MOW than in HW (8 ± 6 vs 5 ± 5, p = 0.004) while at postoperative months 3 and 6, a significant amelioration was found (p = 0.025 and 0.005, respectively). Before BS, no significant differences occurred in the RSES score between MOW and HW (30 ± 7 vs 32 ± 6, p = 0.014), whereas the MOW RSES scores at 6-month post-BS were improved when compared with the HW RSES scores. BS results in a significant improvement in the quality of sexual life, depressive symptoms, and self-esteem in MOW.

In the worldwide context of graft shortage, several strategies have been explored to increase the number of grafts available for liver transplantation (LT). These include the use of marginal and living donors, split livers, and the improvement of marginal donor grafts (machine perfusion). However, recent advances in the understanding of liver organogenesis, stem cells, and matrix biology provide novel insights in tissue engineering. Today, the newest technologies and discoveries open the door to the development of new methods for organ implementation such as the recellularization of natural scaffolds, liver organoids, bio-printing, and tissue or generation of chimeric organs. These approaches might potentially to generate an unlimited source of grafts (allogenic or chimeric) which will be used in the near future for LT or as a temporary bridge toward LT. This qualitative review focuses on all methods of organ implementation and highlights the newest developments in tissue engineering and regenerative medicine.

BACKGROUND: Recent evidence has indicated an increased risk of Barrett's esophagus (BE) in the long term after sleeve gastrectomy (SG). AIM: The aim of the study is to investigate the spectrum of gastroesophageal reflux disease (GERD) symptoms as well as the prevalence of BE, at minimum 5 years after SG in patients who underwent SG in different bariatric centers of two countries: France and Italy. PATIENTS AND METHODS: Five high volume outpatient centers dedicated to bariatric surgery that routinely perform upper GI endoscopy before any bariatric procedures were invited to participate in the study. From January 2017 to June 2018, each center during scheduled postoperative evaluation after surgery asked a minimum 10 consecutive patients, which had performed SG at least 5 years before and with no evidence of BE preoperatively, to undergo another upper GI endoscopy. RESULTS: Ninety (66 F) consecutive patients were enrolled. The mean follow-up was 78 +/- 15 months, and the mean total body weight loss was 25 +/- 12%. The prevalence of BE was 18.8% with no significant difference among centers. Weight loss failure was significantly associated with BE (p \textless 0.01). The prevalence of GERD symptoms, erosive esophagitis, and the usage of PPIs increased from 22%, 10%, and 22% before the SG to 76%, 41%, and 52% at the time of follow-up, respectively (p \textless 0.05). CONCLUSIONS: This multicenter study show a high rate of BE at least 5 years after SG. Weight loss failure was significantly associated with BE. We suggest to provide systematic endoscopy in these patients to rule out this condition.

Gastroesophageal reflux disease (GERD) is present in half of the obese candidates for bariatric surgery. Variability of symptoms and new onset of GERD are often debated. Prior studies have demonstrated that sleeve gastrectomy (SG) is associated with significant weight loss. We prospectively evaluated the effect of a standardized SG technique on GERD symptoms in 104 patients. All patients were surveyed on the presence of heartburn and/or regurgitation with a specific questionnaire (GERD-HRQL). Esophagogastroduodenoscopy (EGDS) was performed in the preoperative phase and after 12 months. All patients completed a 12-month follow-up. In the preoperative phase, 27.9% presented GERD symptoms (29 cases), while endoscopic findings were observed in 19.2% (20 cases). Preoperative GERD was ameliorated/solved in 65.5% of cases. The mean value of the GERD-HRQL score was significantly lower in postoperative evaluation (33.8 vs 19.4; p

The growing number of patients on waiting lists for liver transplantation and the shortage of organs have forced many centers to adopt extended criteria for graft selection, moving the limit of acceptance for marginal livers. Steatotic grafts that were, in the past, considered strictly unacceptable for transplantation because of the high risk of early nonfunction are now considered as a potential resource for organ implementation. Several methods to diagnose, measure, classify, and stage steatosis exist, but none can be considered qualitatively and quantitatively "the ideal method" to date. Clinical, biological, and imaging data can be very helpful to estimate graft steatosis, but histology still remains the gold standard. There is an increasing need for rapid and reliable tools to assess graft steatosis. Herein, we present a comprehensive review of the approaches that are currently used to quantify steatosis in liver grafts.

Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.

Before bariatric surgery (BS), moderate weight loss, left hepatic lobe volume reduction, and micronutrient deficiency (MD) identification and correction are desirable.The objective of this study was to assess the safety and the effectiveness of a 4-week preoperative ketogenic micronutrient-enriched diet (KMED) in reducing body weight (BW), left hepatic lobe volume, and correcting MD in patients scheduled for BS.In this prospective pilot study, a cohort of morbidly obese patients (n = 27, 17 females, 10 males) with a mean body mass index (BMI) of 45.2 kg/m(2) scheduled for BS underwent a 4-week preoperative KMED. Their BW, BMI, fat mass (FM), fat-free mass (FFM), resting metabolic rate (RMR), left hepatic lobe volume, micronutrient status, and biochemical and metabolic patterns were measured before and after the 4-week KMED. Patient compliance was assessed by validated questionnaires (3-day estimated food records and 72-h recall). Qualitative methods (5-point Likert questionnaire) were used to measure diet acceptability and side effects.All patients completed the study. We observed highly significant decreases in BW (- 10.3%, p < 0.001, in males; - 8.2%, p < 0.001, in females), left hepatic lobe volume (- 19.8%, p < 0.001), and an amelioration of patient micronutrient status. All patients showed a high frequency of acceptability and compliance in following the diet. No adverse side effect was reported.This study demonstrates that a 4-week preoperative KMED is safe and effective in reducing BW, left hepatic lobe volume, and correcting MD in obese patients scheduled for BS.

The epidemic of obesity parallels that of chronic kidney disease (CKD). Obesity worsens the course of CKD, mainly defined by an abnormal glomerular filtration rate (GFR). Patients with severe obesity stages (II and III with body mass index >35 kg/m2) are eligible for bariatric surgery (BS), which is the most efficient method of achieving durable weight loss. BS may reverse glomerular hyperfiltration and albuminuria, improve adipocytokine profile, and relieve diabetes and hypertension. Obesity remission after BS might prevent the progression of renal failure in populations with morbid obesity. However, evidence for the beneficial effect of BS on renal function is scant. This lack of knowledge is mainly due to methodologic reasons, which are addressed in this review. The reversibility of hyperfiltration due to the presence of functional renal reserve hampers the interpretation of changes in true GFR after BS. This true GFR is only obtained with the renal clearance of an exogenous filtration marker. Estimation of GFR is generally provided by prediction equations, namely by modification of diet in renal diseases or by chronic kidney disease-epidemiology collaborative group. These equations are not accurate because the serum levels of both creatinine and cystatin C depend on extrarenal factors, which are modified by BS. Comparing the slopes of measured GFR according to various durations of exposure with morbid obesity would be critical in providing reliable data. Herein, we review the current knowledge on the effects of BS on kidney function; we specify the methodologic issues and particularities of the dietary management of CKD patients to propose reliable directions for future clinical research.

Background We recently showed that an 8-week preoperative protein-enriched diet (PED) is associated with significant reductions in body weight and fat mass (FM) without significant loss of fat-free mass (FFM) in morbidly obese patients scheduled for laparoscopic sleeve gastrectomy (LSG).Objectives The objective of this study is to evaluate the impact of PED vs a normal protein diet (NPD) on total weight loss (TWL), FM, FFM, and resting metabolic rate (RMR) in patients after LSG.Methods Before LSG and at 3, 6, and 12 months after, we prospectively measured and compared total body weight (TBW), FM, FFM, and RMR in 60 male patients who received either a NPD (n = 30) with protein intake 1.0 g/kg of ideal body weight, or a PED (n = 30) with protein intake 2.0 g/kg of ideal body weight. Compliance in following the prescribed diet was determined with food frequency questionnaires in all patients. The impact of NPD and PED on renal function was also evaluated.Results Despite non-significant variation in total body weight (TBW), FM decreased more significantly (p < 0.01) with the PED compared to the NPD. In addition, the PED group showed a significantly (p < 0.01) lower decrease in FFM and RMR when compared with the NPD group. Both groups showed high compliance in following the prescribed diets, without negative impact on renal function.Conclusion PED is more effective than NPD in determining FM loss and is associated with a lower decrease in FFM and RMR, without interfering with renal function in male patients after LSG.

Background One of the most effective surgeries for sustainable weight loss in morbidly obese patients is laparoscopic sleeve gastrectomy (LSG). The present study aimed to assess the adherence of LSG patients with respect to following post-operative dietary requirements and micronutrient supplementation, as well as to investigate their perceived barriers in achieving optimal adherence. Methods Retrospective data analysis was performed (3, 6, 9 and 12 months after LSG) using the medical records of 96 morbidly obese patients who had undergone LSG at our institution during 2011–2013. Data collected from patient records were: adherence to prescribed diet; adherence to prescribed consumption of fruit, vegetables, legumes and cereals; use of prescribed micronutrient supplements; and barriers to diet and micronutrient therapy adherence. Data were analysed using spss, version 14.0 (SPSS Inc., Chicago, IL, USA). Results At 3, 6, 9 and 12 months post-LSG, the rates of patient non-adherence to a prescribed diet were 39%, 45%, 51% and 74%, respectively. In particular, there was a low consumption of fruit, vegetables, legumes and cereals compared to the post-surgery prescription. In addition, the rates of patient non-adherence to prescribed micronutrient supplements at 3, 6, 9 and 12 months post-LSG were 43%, 51%, 59% and 67%, respectively. The main reasons for patient non-adherence to diet were poor self-discipline (72%) and poor family support (11%) whereas difficulty swallowing pills or capsules (61%) and cost (20%) were reported as the main barriers to post-LSG adherence. Conclusions Morbidly obese patients who have undergone LSG do not follow exactly the post-operative dietary guidelines, including micronutrient therapy.

Obese patients with preoperative gout often suffer of gouty attacks after bariatric surgery (BS), probably due to the lack of an adequate postoperative diet. Background: Obese patients with preoperative gout often suffer of gouty attacks after bariatric surgery (BS), probably due to the lack of an adequate postoperative diet. Objectives: The objectives of the study are to assess whether sleeve gastrectomy (SG) is effective in reducing the frequency of gouty attacks and also whether a postoperative low-purine diet (LPD) may further reduce these attacks as compared to a normal-purine diet (NPD) in a series of patients suffering of gout before SG. Methods: In this retrospective study, we measured and compared total body weight (TBW), body mass index (BMI), uric acid levels (UAL), anti-gout medication (allopurinol) requirements, and frequency in gouty attacks in 40 patients that underwent SG and who received either a LPD (n=24) or NPD (n=16). Compliance in following the prescribed diet was assessed in both groups study. Results: Before surgery, LPD and NPD patients had hyperuricemia and were receiving allopurinol. One year after SG, LPD and NPD groups showed a significant decrease in serum UAL (p&nbsp

Background Weight loss before laparoscopic sleeve gastrectomy (LSG) is desirable because it can reduce visceral fat and liver size thereby facilitating the surgical procedure. Preoperative very-low-energy diets have been demonstrated to decrease weight, visceral fat, and liver size. However, no studies have been conducted using the Mediterranean-protein-enriched diet (MPED) or on the amount of preoperative weight loss attributed to the loss of fat-free mass (FFM). Objectives To evaluate the effect of the MPED on weight, visceral fat, liver size, fat mass (FM), and FFM in obese patients undergoing LSG. Setting University Hospital, Italy. Materials and Methods Obese male patients (n = 37) with a mean body mass index (BMI) of 45.2 kg/m 2 scheduled for LSG underwent an 8-week preoperative MPED. Their weight, visceral fat, body composition, liver size, and biochemical and metabolic patterns were measured before and after the diet. Patient compliance was assessed by the presence of ketonuria and weight loss. Qualitative methods (5-point Likert questionnaire) were used to measure diet acceptability and side effects. Results We observed highly significant decreases in weight, liver size, visceral fat, and FM; however, there was no significant reduction in FFM. All tested patients showed a high frequency of acceptability and compliance in following the diet, and no secondary effects were observed. Conclusion Based on our findings, we were able to support the hypothesis that MPED might be associated with significant reductions in weight loss, FM, and liver size without a significant loss of FFM.

The development and testing of a portable bioanalytical device which was capable for real-time monitoring of binding assays was demonstrated. The device was based on arrays of nine optoelectronic transducers monolithically integrated on silicon chips. The optocouplers consisted of nine silicon avalanche diodes self-aligned to nine silicon nitride waveguides all converging to a single silicon detector. The waveguides were biofunctionalized by appropriate recognition molecules. Integrated thick polymer microchannels provided the necessary fluidic functions to the chip. A single sided direct contact scheme through a board-to-board receptacle was developed and combined with a portable customized readout and control instrument. Real-time detection of deleterious mutations in BRCA1 gene related to predisposition to hereditary breast/ovarian cancer was performed with the instrument developed using PCR products. Detection was based on waveguided photons elimination through inte raction with fluorescently labeled PCR products. Detection of single biomolecular binding events was also demonstrated using nanoparticles as labels. In addition, label-free monitoring of bioreactions in real time was achieved by exploiting wavelength filtering on photonic crystal engineered waveguides. The proposed miniaturized sensing device with proper packaging and accompanied by a portable instrument can find wide application as a platform for reliable and cost effective point-of-care diagnosis.

Thyroid hormones (TH) are major modulators of energy metabolism and thermogenesis. It is generally believed that 3,5,3'-triiodo-l-thyronine (T3) is the only active form of TH, and that most of its effects are mediated by nuclear T3 receptors, which chiefly affect the transcription of target genes. Some of these genes encode for the proteins involved in energy metabolism. However, a growing volume of evidence now indicates that other iodothyronines may be biologically active. Several mechanisms have been proposed to explain the calorigenic effect of TH, but none has received universal acceptance. Cold acclimation/exposure and altered nutritional status are physiological conditions in which a modulation of energy expenditure is particularly important. TH seem to be deeply involved in this modulation, and this article will review some aspects of their possible influence in these conditions.