Postbariatric surgery hypoglycemia: Nutritional, pharmacological and surgical perspectives.

Post-bariatric hypoglycaemia (PBH) is a metabolic complication of bariatric surgery (BS), consisting of low post-prandial glucose levels in patients having undergone bariatric procedures. While BS is currently the most effective and relatively safe treatment for obesity and its complications, the development of PBH can significantly impact patients' quality of life and mental health. The diagnosis of PBH is still challenging, considering the lack of definitive and reliable diagnostic tools, and the fact that this condition is frequently asymptomatic. However, PBH's prevalence is alarming, involving up to 88% of the post-bariatric population, depending on the diagnostic tool, and this may be underestimated. Given the prevalence of obesity soaring, and an increasing number of bariatric procedures being performed, it is crucial that physicians are skilled to diagnose PBH and promptly treat patients suffering from it. While the milestone of managing this condition is nutritional therapy, growing evidence suggests that old and new pharmacological approaches may be adopted as adjunct therapies for managing this complex condition.

Sex difference in the safety and efficacy of bariatric procedures: a systematic review and meta-analysis.

With the prevalence of obesity alarmingly increasing, it is of primary interest to identify those factors predicting the success of anti-obesity therapeutic strategies currently adopted in clinical practice, and in particular, those of bariatric procedures showing the greatest success in terms of weight loss and maintenance in both the short and long term. Given sex-related differences in psychosocial status, hormonal homeostasis, and body fat distribution, it is likely that the response to different weight management strategies differs by sex. The objective was to elucidate the effect of sex on different bariatric procedures' efficacy and safety outcomes. Searches of PubMed, Cochrane, and Embase databases were performed, followed by hand-searching of reference lists from all relevant articles. We included all the studies evaluating the effect of bariatric procedures on body mass index loss (BMIL), and/or percentage excess weight loss (%EWL), and/or percentage excess body mass index loss, and/or percentage of responders, and/or short-/long-term complications and co-morbidity resolution, broken down by sex. Twenty-seven studies with a total of 114,919 patients were included. Men were more likely to achieve greater BMIL, consistent with higher male baseline BMI, and women were 2.87 times more likely to be classified as weight responders (95% confidence interval [CI]: 1.90-4.34), as well as to perform better in terms of %EWL (95% CI: .13-.54). Upon subgroup analysis based on bariatric procedure, women were more likely to be successful in terms of %EWL upon bioenteric intragastric balloon (BIB) placement (.72, 95% CI: .42-1.02). There was no sex difference regarding investigated co-morbidity resolution (hypertension, diabetes, and obstructive sleep apnea syndrome) or occurrence of short-term complications, whereas women were more likely to develop long-term complications, with an odds ratio of 1.97 (95% CI: 1.57-2.49). Sex does not have a clear effect on efficacy outcomes of bariatric procedures. Differentiating by procedure, BIB may be more effective in women, although results are discordant based on the weight loss outcome considered. If the short-term postoperative complication rate is similar across both sexes, long-term complications occur more frequently in women. To clarify the real effect of sex on bariatric procedure-derived health benefits, it is crucial to report sex-stratified results in future studies, as well as evaluate body composition changes that go beyond simple body weight reduction.

An extra virgin olive oil-enriched chocolate spread positively modulates insulin-resistance markers compared with a palm oil-enriched one in healthy young adults: A double-blind, cross-over, randomised controlled trial.

AIMS: To investigate if extra virgin olive oil (EVOO) or palm oil enriched chocolate spreads consumption leads to different results in terms of plasma ceramides concentration, glucose and lipid metabolism, inflammatory markers and appetite regulation in young healthy subjects. METHODS: In a 2-week, double-blind, cross-over, randomised controlled trial, 20 healthy, normal-weight subjects with a mean age of 24.2 years (SD: 1.2), consumed chocolate spread snacks (73% of energy [%E] from fat, 20% from carbohydrates and 7% from proteins), providing 570 Kcal/day added to an isocaloric diet. The chocolate spreads were identical, except for the type of fat: EVOO oil, rich in monounsaturated fatty acids (MUFAs), or palm oil, rich in Saturated Fatty Acids (SFAs). RESULTS: EVOO-enriched chocolate spread consumption led to better circulating sphingolipids and glucose profile, with reduced plasma ceramide C16:0, ceramide C16:0/ceramide C22:0-ceramide C24:0 ratio and sphingomyelin C18:0 (P = 0.030, P= 0.032 and P = 0.042, respectively) compared to the palm oil-enriched chocolate spread diet. HOMA-IR and plasma insulin were lower, while the Quicki and the McAuley Index were higher after the EVOO diet compared to the palm oil diet (P = 0.046, P = 0.045, P = 0.018 and P = 0.039 respectively). Subjects maintained a stable weight throughout the study. No major significant changes in total cholesterol, triglycerides, HDL, inflammatory markers, and appetite-regulating hormones/visual analogue scale were observed between the groups. CONCLUSIONS: Partially replacing SFAs with MUFAs in a chocolate-based snack as part of a short-term isocaloric diet in healthy individuals may limit SFAs detrimental effects on insulin sensitivity and decrease circulating harmful sphingolipids in young adults.

Platelet Effects of Anti-diabetic Therapies: New Perspectives in the Management of Patients with Diabetes and Cardiovascular Disease.

In type 2 diabetes, anti-thrombotic management is challenging, and current anti-platelet agents have demonstrated reduced efficacy. Old and new anti-diabetic drugs exhibited-besides lowering blood glucose levels-direct and indirect effects on platelet function and on thrombotic milieu, eventually conditioning cardiovascular outcomes. The present review summarizes existing evidence on the effects of glucose-lowering agents on platelet properties, addressing pre-clinical and clinical research, as well as drug-drug interactions with anti-platelet agents. We aimed at expanding clinicians' understanding by highlighting new opportunities for an optimal management of patients with diabetes and cardiovascular disease. We suggest how an improvement of the thrombotic risk in this large population of patients may be achieved by a careful and tailored combination of anti-diabetic and anti-platelet therapies.

Hobnail variant of papillary thyroid carcinoma showing goiter-like presentation and rapid growth.

SUMMARY: We present the case of a 47-year-old Caucasian previously healthy woman with a voluminous thyroid nodule occupying almost the entire anterior neck region. The lesion had progressively increased in size during the previous 3 months and the patient presented intermittent symptoms of dysphagia and odynophagia with a slight change in voice. Fine needle aspiration showed papillary carcinoma. Based on imaging and cytological findings, the patient underwent total thyroidectomy. The surgical sample revealed a totally enlarged thyroid gland (weight: 208 g) with the presence of a poly-lobulated lesion centrally located and involving the isthmus and both lobes. Hobnail features were present in more than 30% of the neoplastic cells in agreement with the criteria for this subtype. Psammoma bodies and focal necrosis were also present. The extra-thyroidal extension included strap muscles and peri-esophageal glands. Immunohistochemistry using VE1 antibody for detecting BRAF-V600E mutation resulted positive. The final diagnosis was papillary thyroid carcinoma (PTC) hobnail variant (HVPTC)-pT4a. The HVPTC is a rare entity and, in most cases, appears like a unifocal lesion with a maximum tumor size of 8 cm reported so far. To our knowledge, this represents the largest tumor ever described (14 cm), showing rapid growth and with multinodular goiter-like aspect. LEARNING POINTS: HVPTC is an aggressive variant of PTC, usually associated with radioactive iodine refractoriness, and a higher mortality rate compared to classic PTC. However, there is a marked individual variability in this association. HVPTC usually appears as small unifocal lesion but a multinodular goiter presentation may occur. The present case highlights that despite of the histology, our patient achieved a high ablation success rate after radioactive iodine therapy.

Donor Preconditioning with Inhaled Sevoflurane Mitigates the Effects of Ischemia-Reperfusion Injury in a Swine Model of Lung Transplantation.

Primary graft dysfunction (PGD) and ischemia-reperfusion injury (IRI) occur in up to 30% of patients undergoing lung transplantation and may impact on the clinical outcome. Several strategies for the prevention and treatment of PGD have been proposed, but with limited use in clinical practice. In this study, we investigate the potential application of sevoflurane (SEV) preconditioning to mitigate IRI after lung transplantation. The study included two groups of swines (preconditioned and not preconditioned with SEV) undergoing left lung transplantation after 24-hour of cold ischemia. Recipients' data was collected for 6 hours after reperfusion. Outcome analysis included assessment of ventilatory, hemodynamic, and hemogasanalytic parameters, evaluation of cellularity and cytokines in BAL samples, and histological analysis of tissue samples. Hemogasanalytic, hemodynamic, and respiratory parameters were significantly favorable, and the histological score showed less inflammatory and fibrotic injury in animals receiving SEV treatment. BAL cellular and cytokine profiling showed an anti-inflammatory pattern in animals receiving SEV compared to controls. In a swine model of lung transplantation after prolonged cold ischemia, SEV showed to mitigate the adverse effects of ischemia/reperfusion and to improve animal survival. Given the low cost and easy applicability, the administration of SEV in lung donors may be more extensively explored in clinical practice.

The Mediterranean diet increases glucagon-like peptide 1 and oxyntomodulin compared with a vegetarian diet in patients with type 2 diabetes: A randomized controlled cross-over trial.

AIM: To compare a Mediterranean diet (MED) with a high-fibre vegetarian diet (HFV) in terms of hunger-satiety perception through post-prandial assessment of appetite-related hormones glucagon-like peptide 1 (GLP-1) and oxyntomodulin, as well as self-rated visual analogue scale (VAS) quantification, in overweight/obese subjects with type 2 diabetes (T2D). MATERIALS AND METHODS: Twelve T2D subjects (Male to female ratio = 7:5), mean age 63 ± 8.5 years, were enrolled in a randomized, controlled, crossover study. Participants consumed an MED meal as well as an isocaloric meal rich in complex carbohydrate as well as an isocaloric MED meal in two different visits with a 1-week washout period between the two visits. Appetite ratings, glucose/insulin, and gastrointestinal hormone concentrations were measured at fasting and every 30' until 210' following meal consumption. RESULTS: GLP-1 and oxyntomodulin levels were significantly higher following MED meal compared with HFV meals (210' area under the curve, p < 0.022 and p < 0.023, respectively). Both MED and HFV meal resulted in a biphasic pattern of GLP-1 and oxyntomodulin, although MED meal was related to a delayed, significantly higher second GLP-1 peak at 150' compared with that of HFV meal (p < 0.05). MED meal was related to lower glucose profile compared with HFV meal (p < 0.039), whereas we did not observe significant changes in terms of self-reported VAS scores and insulin trend. CONCLUSIONS: In T2D overweight/obese subjects, an MED meal is more effective than a HFV meal in terms of post-prandial plasma glucose homoeostasis and GLP-1 and oxyntomodulin release. These changes were not confirmed by VAS appetite self-assessment over a 210' period.

Prognosis of patients with differentiated thyroid carcinomas having a preoperative cytological report of indeterminate at low or high risk. A multicenter study.

BACKGROUND: Italian cytology system for thyroid fine-needle aspiration (FNA) includes indeterminate lesions at low- (Tir 3A) and high-risk (Tir 3B). The present retrospective multicenter study was undertaken to compare the histological type of cancers and disease-free survival in these two groups. METHODS: Eight institutions participated. Thyroid cancer patients diagnosed and followed-up after Tir 3A or Tir 3B were reviewed. Histological diagnosis was adopted as the gold standard. Patients were defined with cancer recurrence or no evidence of disease. Disease-free survival (DFS) was calculated. A non-parametric statistical analysis was used. DFS was estimated by Kaplan-Meier method and Hazard Ratio (HR) defined the slope of curves. RESULTS: Two hundred and nine patients (median DFS 24 months) were enrolled and a 6.3% of these recurred. Tir 3B group had higher age (p = 0.014), larger cancer size (p = 0.0002), shorter DFS (p = 0.003), higher number of aggressive cancers (p = 0.006), and relapse frequency double than Tir 3A. At survival curves analysis, Tir 3B group had HR of 2.37 with respect to Tir 3A. At Cox's proportional hazard regression analysis histology was the only significant predictor of relapse. CONCLUSIONS: While patients with thyroid FNA of Tir 3B should be addressed to surgery due to high likelihood of more aggressive cancer, a diagnostic surgery could be avoided in patients with Tir 3A if concurrent unsuspicious clinical features are found.

A comprehensive protocol for physiokinesis therapy and enhanced recovery after surgery in patients undergoing video-assisted thoracoscopic surgery lobectomy.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy has recently been adopted as the gold standard surgical option for the treatment of early stage non-small cell lung cancer. Enhanced recovery after surgery (ERAS) is being progressively adopted in thoracic surgery to improve the postoperative outcomes. Even if the benefits of ERAS are universally accepted, to date a standardized and uniform approach has not been described in the medical literature. The Italian VATS group has recently proposed to include in the VATS lobectomy database a structured protocol for ERAS. METHODS: The ERAS section of the Italian VATS group is proposing a comprehensive ERAS protocol within the VATS lobectomy database, allowing the prospective collection of a dedicated set of data. Separate sections of the protocol are dedicated to different topics of ERAS. This study is specifically dedicated to the section of physiokinesis therapy. The medical literature will be extensively reviewed and a physiotherapy (PT) protocol of ERAS will be presented and discussed. A seta of structured clinical pathways will also be suggested for adoption in the VATS Group database. DISCUSSION: Pre- and post-operative adoption of an ERAS protocol in patients undergoing VATS lobectomy may promote an improved post-operative course, a shorter hospital stay and an overall more comfortable patients' experience. The mainstays of a physiokinesis therapy ERAS protocol are patients' education, constant physical and respiratory therapy sessions, and adoption of adequate devices. Although many studies have investigated the usefulness of physical and respiratory physiokinesis therapy, a comprehensive ERAS protocol for VATS lobectomy patients has not yet been described. The proposed ERAS platform, adopted by the VATS Group database, will contribute to a prospective data collection and allow a scientific analysis of the results.

A brief introduction to probability.

The theory of probability has been debated for centuries: back in 1600, French mathematics used the rules of probability to place and win bets. Subsequently, the knowledge of probability has significantly evolved and is now an essential tool for statistics. In this paper, the basic theoretical principles of probability will be reviewed, with the aim of facilitating the comprehension of statistical inference. After a brief general introduction on probability, we will review the concept of the "probability distribution" that is a function providing the probabilities of occurrence of different possible outcomes of a categorical or continuous variable. Specific attention will be focused on normal distribution that is the most relevant distribution applied to statistical analysis.

Erratum to nodal management and upstaging of disease: initial results from the Italian VATS Lobectomy Registry.

[This corrects the article DOI: 10.21037/jtd.2017.06.12.].

Nodal management and upstaging of disease: initial results from the Italian VATS Lobectomy Registry.

BACKGROUND: VATS lobectomy is an established option for the treatment of early-stage NSCLC. Complete lymph node dissection (CD), systematic sampling (SS) or resecting a specific number of lymph nodes (LNs) and stations are possible intra-operative LN management strategies. METHODS: All VATS lobectomies from the "Italian VATS Group" prospective database were retrospectively reviewed. The type of surgical approach (CD or SS), number of LN resected (RN), the positive/resected LN ratio (LNR) and the number and types of positive LN stations were recorded. The rates of nodal upstaging were assessed based on different LN management strategies. RESULTS: CD was the most frequent approach (72.3%). Nodal upstaging rates were 6.03% (N0-to-N1), 5.45% (N0-to-N2), and 0.58% (N1-to-N2). There was no difference in N1 or N2 upstaging rates between CD and SS. The number of resected nodes was correlated with both N1 (OR =1.02; CI, 1.01-1.04; P=0.03) and N2 (OR =1.02; CI, 1.01-1.05; P=0.001) upstaging. Resecting 12 nodes had the best ability to predict upstaging (6 N1 LN or 7 N2 LN). The finding of two positive LN stations best predicted N2 upstaging [area under the curve (AUC) of receiver operating characteristic (ROC) =0.98]. CONCLUSIONS: Nodal upstaging (and, indirectly, the effectiveness of intra-operative nodal management) cannot be predicted based on the surgical technique (CD or SS). A quantitative assessment of intra-operative LN management may be a more appropriate and measurable approach to justify the extension of LN resection during VATS lobectomy.

Video-assisted thoracic surgery lobectomy in patients with reduced pulmonary function: a single-center series.

Video-assisted thoracic surgery (VATS) is currently considered a 'gold standard' approach for pulmonary lobectomy in patients with early-stage lung cancer, displaying equal or superior results compared with an open traditional approach. In patients with limited pulmonary function, VATS lobectomy may reduce the impact of surgery and allow outcomes similar to patients with normal pulmonary function. The preliminary analysis of our initial, single center series of VATS lobectomy showed less complications and shorter postoperative length of stay compared with a historical series of open lobectomy patients. Patients with reduced predicted preoperative FEV1% (ppoFEV1%) who underwent VATS lobectomy had similar outcomes compared with patients with normal ppoFEV1, but longer postoperative length of stay.

ISMETT: An International Collaboration on Organ Transplantation.

The Institute of the Mediterranean for Transplantation and High Specialty Therapies (ISMETT) is a multi-organ transplant and high specialty center located in Palermo, Italy and managed by the University of Pittsburgh Medical Center. Clinical transplant activity started in 1999 and, herein, we illustrate the outcomes achieved over the past 15 years. In total, ISMETT has performed 997 liver transplants (83.9% adults, 16.1% pediatrics) with a significant percentage of liver transplants from cadaver split livers (17%) and partial grafts from living donors (11.5%). Among liver transplant recipients, the overall five-year graft survival was 74.3% in the adult population and 79% in the pediatric population. ISMETT has also performed 419 kidney transplants in total: 211 from cadaveric donors (22 double), 176 from living donors, and 32 combined (19 with liver, 11 with pancreas, and 2 with heart). The 5-year renal graft survival was 82.2% (cadaveric donor) and 92.2% (living donor). More recently, in 2005, ISMETT started pancreas, lung, and heart transplant programs. In total, 16 pancreas transplants have been performed, of which 12 were simultaneous pancreas-kidney transplants, 1 was pancreas after kidney, and 3 were pancreas alone transplants. One pancreatic islet transplant was also performed in a patient who had already undergone kidney transplantation. Patient and pancreas graft survivals at 1 year were 86.7% and 73.3%, respectively, and 80% and 73.3% at five years (pancreas survival is defined as normoglycemia and insulin-independence). Lung transplant has been performed in 133 patients (116 double and 17 single lung). Eleven were pediatric (8% of all transplants). The 1-month, 1-year, and 5-year overall graft survivals were, 93.8%, 81.4%, and 75.6%, respectively. Heart transplantation has been performed in 133 adults (85% were male). Coronary artery disease and cardiomyopathy were the leading underlying heart disease diagnoses leading to transplant. Mechanical support (ventricular assist device or extracorporeal membrane oxygenation) as a bridge to transplant was used in 18% of the heart transplant cases. One-year heart graft survival was 83% and 5-year heart graft survival was 81%.

Metastasis at a tracheostomy site as the presenting sign of late recurrent breast cancer.

BACKGROUND: Metastasis in a tracheostomy site occurs rarely, usually from head and neck primary tumors. Breast cancer relapse to a tracheostomy has not been described to date. METHODS AND RESULTS: A 71-year-old women presented with symptoms typical of central airway obstruction, 10 years after mastectomy for breast cancer. Fifteen months before admission, when cancer follow-up was negative, she also had surgery for cerebral aneurysm and a tracheostomy. On admission, CT showed a solid mass infiltrating the tracheostomy tract and projecting into the airway. Tracheal obstruction palliation was achieved by laser resection of the endotracheal growth and stenting. Histology documented breast cancer metastasis. CONCLUSIONS: Tracheostomy site metastasis was the presenting sign of late-onset relapse of breast cancer. This case supports the concept of surgery-driven interruption of micrometastatic cancer dormancy, in that the initial recurrence developed in a tracheostomy that was surgically created several years after resection of the primary tumor.