Long-term efficacy and safety of percutaneous ethanol injection (PEI) in cystic thyroid nodules: A systematic review and meta-analysis.

BACKGROUND: Percutaneous ethanol injection (PEI) is used for the treatment of benign cystic thyroid nodules. This systematic review and meta-analysis aimed to obtain strong evidence of its long-term efficacy and safety. METHODS: PubMed, CENTRAL, Scopus and Web of Science databases were searched until November 2020 for studies reporting data on volume reduction rate (VRR), compressive symptoms and cosmetic concerns. Associated complications were assessed. A random-effects model was designed to pool the data. RESULTS: Out of 385 papers, nine studies evaluating 1667 nodules were finally included. Overall, VRR at 6, 12, 24, 36, 60 and 120 months was 77%, 81%, 72%, 68%, 74% and 69%, respectively. Significant reductions in the compressive symptoms and cosmetic concerns were observed. No permanent complications were observed. CONCLUSIONS: The present meta-analysis showed that PEI could significantly reduce the volume of benign cystic thyroid nodules. This reduction was already effective at 6 months post-treatment, and the effect was stable over time.

Fibrosis-4 Index vs Nonalcoholic Fatty Liver Disease Fibrosis Score in Identifying Advanced Fibrosis in Subjects With Nonalcoholic Fatty Liver Disease: A Meta-Analysis.

INTRODUCTION: In subjects with nonalcoholic fatty liver disease (NAFLD), advanced fibrosis (AF) carries the highest risk of adverse liver-related events. To reduce the number of unnecessary biopsies, several noninvasive tools (NITs) for the risk stratification of fibrosis have been developed. We conducted this meta-analysis to assess the performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis scores (NFS), the 2 most common NITs, for the appropriate selection of subjects with AF for biopsy. METHODS: Four databases were searched until December 2020 (CRD42021224766). Original articles reporting data on the performance of FIB-4 and NFS, interpreted according to standard cutoffs in subjects with biopsy-proven NAFLD, were included. Separate data extractions were performed according to the lower cutoff, the higher cutoff, and the dual threshold approach. The numbers of subjects classified as true-negative, true-positive, false-negative, and false-positive were extracted. Summary operating points were estimated using a random-effects model. RESULTS: Eighteen studies evaluating 12,604 subjects were included. Participants were adult outpatients with biopsy-proven NAFLD or nonalcoholic steatohepatitis. Overall, a weak-to-moderate performance was found for both scores. The head-to-head comparison showed FIB-4 to be associated with a higher performance in ruling in and NFS in ruling out AF in the single threshold approach, whereas, with the dual threshold approach, a lower prevalence of indeterminate findings was found for FIB-4. DISCUSSION: This meta-analysis suggested that currently available NITs have a limited performance in identifying AF among subjects with NAFLD. Further studies are needed to optimize existing thresholds or develop new NITs.

How to better stratify the risk of differentiated thyroid carcinomas: the key role of radioactive iodine therapy, age, and gender.

PURPOSE: The risk of relapse of differentiated thyroid carcinomas (DTC) and their indication for radioactive iodine therapy (RAI) are assessed according to ATA risk stratification system principally based on tumor-nodes-metastasis (TNM) staging. However, while establishing the indication for RAI may be a "dilemma," performing it can improve the risk stratification. We aimed to evaluate whether (1) the stratification of risk of recurrence differs when TNM is considered with or without peri-RAI findings and (2) the assessment of the risk of disease-specific mortality is improved by adding age and gender. METHODS: From our database, all DTC patients treated with thyroidectomy and RAI from 1992 to 2017 were included. Subjects with a follow-up shorter than 1 year and positive thyroid antibodies were excluded. Patients were classified into (1) a three-category ATA model based on TNM (basic model) and (2) a five-category model based on TNM plus peri-RAI findings, i.e., thyroglobulin and 131I whole-body scan (advanced model). Relapse was proven by histology and/or imaging. Differences in disease-free survival (DFS) and overall survival (OS) were assessed. RESULTS: We enrolled 907 patients; of these, 4.4% died and 21% suffered recurrence. According to the basic model, there were 11.8% high-risk, 32.9% intermediate-risk, and 55.3% low-risk patients. According to the advanced model, 29.9% of patients were re-classified in a higher risk category and the five categories of this model displayed significantly different risks of relapse and death. The estimate of DFS was significantly higher in the advanced model than in the basic one (ΔC-index = + 6.8%, P < .001). By adding age and gender to the advanced model, the highest performance in predicting death was achieved (ΔC-index = + 5.1%, P < .001). CONCLUSIONS: The peri-RAI findings are essential in order to carefully stratify the risk of DTC recurrence. Integrating these data with age and gender enables those cases at highest risk of death to be identified.

The ultrasound risk stratification systems for thyroid nodule have been evaluated against papillary carcinoma. A meta-analysis.

Thyroid imaging reporting and data systems (TIRADS) are used to stratify the malignancy risk of thyroid nodule by ultrasound (US) examination. We conducted a meta-analysis to evaluate the pooled cancer prevalence and the relative prevalence of papillary, medullary, follicular thyroid cancer (PTC, MTC, and FTC) and other malignancies among nodules included in studies evaluating their performance. Four databases were searched until February 2020. Original articles with at least 1000 nodules, evaluating the performance of at least one TIRADS among AACE/ACE/AME, ACR-TIRADS, ATA, EU-TIRADS, or K-TIRADS, and reporting data on the histological diagnosis of malignant lesions were included. The number of malignant nodules, PTC, FTC, MTC and other malignancies in each study was extracted. For statistical pooling of data, a random-effects model was used. Nine studies were included, evaluating 19,494 thyroid nodules. The overall prevalence of malignancy was 34% (95%CI 21 to 49). Among 6162 histologically proven malignancies, the prevalence of PTC, FTC, MTC and other malignancies was 95%, 2%, 1%, and 1%, respectively. A high heterogeneity was found for all the outcomes. A limited number of studies generally conducted using a retrospective design was found, with possible selection bias. Acknowledging this limitation, TIRADSs should be regarded as accurate tools to diagnose PTC only. Proposed patterns and/or cut-offs should be revised and other strategies considered to improve their performance in the assessment of FTC, MTC and other malignancies.

Ultrasound systems for risk stratification of thyroid nodules prompt inappropriate biopsy in autonomously functioning thyroid nodules.

OBJECTIVE: Ultrasound (US) risk stratification systems (RSSs) have been developed to reduce the number of unnecessary fine-needle aspiration (FNA) biopsies in patients with thyroid nodules. Autonomously functioning thyroid nodules (AFTN) account for 5%-10% of palpable lesions and are very rarely malignant. The present study was undertaken to investigate how RSSs classify AFTNs and whether RSSs are able to avoid unnecessary FNA biopsies in such cases. METHODS: Patients with AFTN who had undergone US, scintigraphy and thyroid function evaluation from December 2016 to December 2017 were selected. US images were retrospectively reviewed and AFTN reclassified according to AACE/ACE/AME, ACR-TIRADS, ATA, BTA, EU-TIRADS, K-TIRADS and TIRADS. Risk class and indication for FNA were assessed. RESULTS: A number of 87 AFTNs from 85 consecutive patients were enrolled. A median diameter of 22 mm (range 10-59) was found, with an ovoid isoechoic nodule being the most frequent US presentation. When AFTNs were reclassified according to US RSSs, the most common categories were low and intermediate risk. AFTNs were assessed as being at high risk/high suspicion/malignant in 1%-9%, with good agreement among AACE/ACE/AME, ATA, EU-TIRADS, K-TIRADS and TIRADS. Remarkably, FNA was indicated in 27%-90% of AFTNs. A statistically significant difference among the systems was found; 8% of cases were nonclassifiable by one or more US RSS. CONCLUSIONS: Ultrasound RSSs prompt inappropriate FNA in a significant number of patients with AFTN.

Generalizability of sodium-glucose co-transporter-2 inhibitors cardiovascular outcome trials to the type 2 diabetes population: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular outcome trials of sodium-glucose co-transporter-2 inhibitors (SGLT2i CVOTs) found the agents to be associated with clinical benefits in terms of cardiovascular and renal outcomes. We performed a meta-analysis to assess and compare the overall prevalence of eligibility for the enrollment criteria of CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, and VERTIS-CV among unselected patients with type 2 diabetes. METHODS: This meta-analysis was registered in PROSPERO (CRD42020172032). PubMed, CENTRAL, Scopus and Web of Science were researched in March 2020. Studies evaluating the prevalence of eligibility for each SGLT2i CVOT were selected. Endpoints were estimated using a random-effects model. RESULTS: Five studies, evaluating 1,703,519 patients with type 2 diabetes, were included. Overall, the prevalence of eligible patients according to the enrollment criteria of CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, and VERTIS-CV was 36.4%, 49.5%, 17.0% and 19.0%, respectively. In head-to-head comparisons, DECLARE-TIMI 58 was associated with the highest odds of eligibility (1.74 versus CANVAS, 5.15 versus EMPA-REG OUTCOME and 4.81 versus VERTIS-CV), followed by CANVAS and EMPA-REG OUTCOME/VERTIS-CV. A high heterogeneity was found for all the outcomes. CONCLUSIONS: The present review showed that a considerable number of patients counseled in clinical practice could have been eligible for SGLT2i CVOTs. Particularly, dapagliflozin was shown to be the SGLT2i with the largest generalizability of findings from its CVOT according to the odds ratio of eligibility for the enrollment criteria among unselected patients with type 2 diabetes. Further country- or region-specific studies are needed to confirm the applicability of our results.

Confusion in the nomenclature of ketogenic diets blurs evidence.

Ketogenic diets have been proposed as a non-pharmacological strategy for the management of several chronic conditions. Their efficacy and safety have been evaluated in the field of neurology, oncology and endocrinology for disorders including cancer, dementia, drug-resistant epilepsy, migraines, obesity, polycystic ovary syndrome and type 2 diabetes mellitus. The nutritional requirements of these subjects are expected to differ significantly. Indeed, although all ketogenic diets restrict carbohydrates, each intervention is characterized by a specific daily calorie intake, macronutrient composition and duration. However, the adopted nomenclature was often unclear to the general reader; also, the same abbreviations for different protocols were used. This possibly resulted in mistakes in the interpretation of the available evidence and limited the impact of studies on the topic in the clinical practice. Adopting a clear and consistent vocabulary is key in any context. Here, we present a practical and clinically-based proposal for the classification and abbreviation of ketogenic diets.

Efficacy and safety of very low calorie ketogenic diet (VLCKD) in patients with overweight and obesity: A systematic review and meta-analysis.

Very low calorie ketogenic diet (VLCKD) has been proposed as a promising option to achieve a significant weight loss in a short time period. We conducted a systematic review and meta-analysis to evaluate its efficacy and safety in patients with overweight and obesity. Four databases were searched on May 2019. Studies reporting data on body weight, body mass index (BMI), waist circumference, body composition, blood pressure, HbA1c, lipids, and markers of liver and kidney function were selected. Discontinuation was also assessed. Twelve studies were included. VLCKD was associated with weight losses of -10.0 kg (I2 = 6%) and - 15.6 kg (I2 = 37%) in studies with a ketogenic phase up to and of at least four weeks, respectively. The weight lost during the ketogenic phase was stable in the subsequent follow-up up to two years (p = 0.12). Also, VLCKD was associated with reductions of BMI (-5.3 kg/m2), waist circumference (-12.6 cm), HbA1c (-0.7%), total cholesterol (-28 mg/dl), triglycerides (-30 mg/dl), AST (-7 U/l), ALT (-8 U/l), GGT (-8 U/l), systolic and diastolic blood pressure (-8 and - 7 mmHg, respectively). No changes in LDL cholesterol, HDL cholesterol, serum creatinine, serum uric acid and serum potassium were found. Serum sodium increased during VLCKD (+1.6 mEq/l). The overall prevalence of patients discontinuing VLCKD was 7.5% and this was similar to patients undergoing a low calorie diet (p = 0.83). The present review supports the use of VLCKD as an effective strategy for the management of overweight and obesity. Future guidelines should include a specific recommendation for this intervention.

Ketogenic diets as treatment of obesity and type 2 diabetes mellitus.

During the last decades, several interventions for the management of overweight and obesity have been proposed. Among diets, the first studies focused on the effect of water only and total fasting diets with or without proteins. Unfortunately, they were found to be associated with adverse events which lead to the abandon of these strategies. Interestingly, despite the radical approach, total fasting was effective and generally well tolerated. A strict connection between protein-calorie malnutrition and increased in morbidity and mortality in hospitalized patients was found at that time. Then, the seminal works of Blackburn and his collaborators lead to the introduction of the protein-sparing modified fast. Encouraged by the early results using this intervention, diets evolved to the current very-low-calorie ketogenic diets (VLCKD). In the present review, results of studies on the VLCKDs are presented and discussed, with a particular reference to the protocolled VLCKD. Also, a recent proposal on the nomenclature on the ketogenic diets is reported. Available evidence suggests VLCKDs to be effective in achieving a rapid and significant weight loss by means of an easily reversible intervention which could be repeated, if needed. Muscle mass and strength are preserved, resting metabolic rate is not impaired, hunger, appetite and mood are not worsened. Symptoms and abnormal laboratory findings can be there, but they have generally been reported as of mild intensity and transient. Preliminary studies suggest VLCKDs to be a potential game-changer in the management of type 2 diabetes too. Therefore, VLCKDs should be considered as an excellent initial step in properly selected and motivated patients with obesity or type 2 diabetes, to be delivered as a part of a multicomponent strategy and under strict medical supervision.

Performance of contrast-enhanced ultrasound (CEUS) in assessing thyroid nodules: a systematic review and meta-analysis using histological standard of reference.

BACKGROUND: The present study was undertaken to systematically review the literature on the reliability of using contrast-enhanced ultrasound (CEUS) to assess thyroid nodules. To avoid the potential bias in studies using a cytological standard of reference, here we aimed to meta-analyze data from studies adopting histological diagnosis as the gold standard. METHODS: A comprehensive literature exploration of PubMed and Scopus was conducted. The search was updated until June 2018 and references of the retrieved articles screened. Only original articles reporting the histological follow-up of nodules previously undergone CEUS evaluation were eligible for inclusion. Pooled sensitivity, specificity, PPV, and NPV of CEUS were calculated by DerSimonian and Laird method (random-effects model). RESULTS: The literature search retrieved 1885 articles, and 14 were included for the study. There were Chinese, Italian, German, and Austrian authors. All studies used SonoVue. The overall number of reported nodules was 1515, of which 775 were classified as positive at CEUS and 740 as negative. Pooled sensitivity, specificity, PPV, and NPV of CEUS were 85% (95% CI 83-88), 82% (95% CI 77-87), 83% (95% CI 77-88), and 85% (95% CI 81-88), respectively. Moderate inconsistency was present for specificity and PPV. There was publication bias for sensitivity and NPV. CONCLUSIONS: CEUS reaches good performance in discriminating between malignant and benign thyroid lesions.

GLP-1 receptor agonist added to insulin versus basal-plus or basal-bolus insulin therapy in type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: Current guidelines recommend that antihyperglycaemic treatment in patients with type 2 diabetes not achieving the HbA1c target on basal insulin should be intensified with a glucagon-like peptide-1 receptor agonist (GLP-1RA) or basal-plus/basal-bolus (BP/BB) insulin regimen. We conducted a systematic review and meta-analysis to compare the effects of GLP-1RA/insulin combinations versus BP/BB. METHODS: The review was registered on PROSPERO (CRD42017079547). PubMed, Scopus, CENTRAL, and ClinicalTrials.gov were searched until July 2018. All randomized controlled trials (RCTs) reporting HbA1c , body weight, daily insulin dose, hypoglycaemic events, and discontinuation due to lack of efficacy were included. A subgroup analysis on different combinations of GLP-1RA and insulin was performed. RESULTS: Out of 1885 retrieved papers, 13 RCTs were included in the review. Compared with BP/BB, GLP-1RA/insulin combinations were associated with a similar HbA1c reduction (Δ = -0.06%; 95% confidence interval [CI], -0.14 to 0.02; P = 0.13; I2  = 52%), greater weight loss (Δ = -3.72 kg; 95% CI, -4.49 to -2.95; P < 0.001; I2  = 89%), and lower incidence of hypoglycaemic events (relative risk [RR] = 0.46; 95% CI, 0.38-0.55; P < 0.001; I2  = 99%). The daily insulin dosage among GLP-1RA/insulin users was 30.3 IU/day (95% CI, -41.2 to -19.3; P < 0.001; I2  = 94%), lower than with BP/BB. No difference was found for discontinuation due to lack of efficacy. CONCLUSIONS: The present review supports treatment intensification with GLP-1RA added to insulin versus BP/BB in uncontrolled type 2 diabetes. This could provide similar antihyperglycaemic efficacy while leading to weight loss and sparing of hypoglycaemia and insulin dose. As a consequence, a considerable number of patients with type 2 diabetes could be potentially shifted from BP/BB to GLP-1RA/insulin combinations.

Unstimulated high-sensitive thyroglobulin is a powerful prognostic predictor in patients with thyroid cancer.

Background Differentiated thyroid carcinoma (DTC) has an excellent prognosis and the role of high-sensitive thyroglobulin measured during levothyroxine (ON-T4 hs-Tg) testing to discriminate patients with structural from not-evidence of disease (SED and NED, respectively) has been investigated. We conducted a systematic review and meta-analysis evaluating the performance of ON-T4 hs-Tg in two clinical scenarios considering its negative predictive value (NPV) as primary outcome: (1) diagnostic performance of Tg when undetectable value and NED status are simultaneously demonstrated; (2) prognostic performance of undetectable Tg in predicting NED in the subsequent follow-up. Methods This systematic review and meta-analysis were registered on PROSPERO (CRD42019125092). PubMed, Scopus, CENTRAL and Web of Science were searched until February 12, 2019. Original articles reporting data on SED/NED in patients with detectable/undetectable ON-T4 hs-Tg were selected. Summary operating points were estimated using a random-effects model. Results Out of 1413 retrieved papers, 10 studies evaluating 1796 patients were included. Participants were outpatients diagnosed with DTC, treated with near-total (NTx) or total thyroidectomy (TTx) with or without radioactive iodine (RAI). The NPV of ON-T4 hs-Tg for diagnostic and prognostic performance was 99.4% (95% CI 98.9-99.9; I2 = 13%) and 99.4% (95% CI 98.8-100; I2 = 0%), respectively. Conclusions Our findings show that ON-T4 hs-Tg is an excellent diagnostic tool and prognostic factor to rule-out SED. A high level of evidence is provided to decrease the intensity and frequency of follow-up in those DTC patients having undetectable high-sensitive Tg.

Efficacy and safety of MWA versus RFA and CA for renal tumors: A systematic review and meta-analysis of comparison studies.

PURPOSE: Thermal ablation procedures represent an alternative treatment option for patients with T1a renal tumors. Radiofrequency ablation (RFA) and cryoablation (CA) are the most used and studied techniques, while microwave ablation (MWA) has progressively emerged in recent years. Our aim was to assess the effectiveness and safety of MWA in comparison to RFA and CA for the treatment of primary renal tumors. METHOD: Pubmed, CENTRAL, Web of Science and Scopus were searched until March 2023 to identify studies aimed at comparing the efficacy and safety of MWA with those of RFA and CA for the treatment of patients with primary renal tumors. We compared MWA and RFA/CA primary technique efficacy, local recurrences, overall and cancer-specific survival, major and overall complications, and eGFR changes. Moreover, subgroup analyses were conducted (MWA vs RFA; MWA vs CA; MWA vs RFA/CA in T1a renal tumors). RESULTS: Ten retrospective studies with 2258 thermal ablations were included (508 MWA and 1750 RFA /CA). MWA had fewer local recurrences (OR = 0.31; 95% CI, 0.16, 0.62; p = 0.0008) than RFA/CA; the other outcomes were not significantly different. In subgroup analyses, MWA resulted to have fewer overall complications than RFA (OR = 0.60; 95% CI, 0.38, 0.97; p = 0.04) and CA (OR = 0.49; 95% CI, 0.28, 0.85; p = 0.01); moreover, MWA was associated with fewer recurrences than CA (OR = 0.30; 95% CI, 0.11, 0.84; p = 0.02). In T1a renal tumors subgroup analysis, the outcomes were not significantly different. CONCLUSIONS: MWA is an ablative procedure as effective and safe as RFA or CA for the treatment of renal tumors.

Thyroid Nodules with Indeterminate FNAC According to the Italian Classification System: Prevalence, Rate of Operation, and Impact on Risk of Malignancy. An Updated Systematic Review and Meta-analysis.

A thyroid nodule classified as indeterminate on fine-needle aspiration cytology (FNAC), hereafter referred to as an indeterminate thyroid nodule (ITN), represents a clinical dilemma. The Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) divides ITNs into low- and high-risk categories (i.e., TIR3A and TIR3B, respectively) to better manage patients. This study aimed to achieve high-evidence estimates of the prevalence, rate of operation, and risk of malignancy of ITNs, including TIR3A and TIR3B ITNs. This systematic review was conducted according to MOOSE to retrieve all original studies citing ICCRTC. The last search was performed in February 2022. The risk of bias of the included studies was assessed. Separate proportion meta-analyses were performed with a random-effect model using OpenMeta[Analyst]. The online search processed 271 studies, and 33 were finally considered. First, the cancer prevalence among ITNs was 32.4%. Second, the cancer prevalence among TIR3As was 12.4%, with heterogeneity (I2 90%) explained by a linear correlation between sample size and cancer rate (p = 0.009). Third, the cancer prevalence among TIR3Bs was 44.4%, with heterogeneity (I2 75%) explained by the inverse correlation between sample size and cancer rate (p = 0.031). Fourth, the prevalence of ITNs, TIR3A, and TIR3B among FNACs was 29.6%, 12.6%, and 12.9%, respectively, with sample size and TIR3B prevalence being inversely correlated (p = 0.04). Fifth, the operation rates of ITNs, TIR3A, and TIR3B were 54.3%, 48.3%, and 75.2%, respectively, and the sample size and TIR3A operation rate were inversely correlated (p = 0.010). These data strongly support the division of ITNs into low- and high-risk subcategories. Importantly for clinical practice, the cancer rate among ITNs is significantly influenced by the study sample size.

Very-low-calorie ketogenic diet for the management of obesity, overweight and related disorders.

INTRODUCTION: Very-low-calorie ketogenic diet (VLCKD) is a promising lifestyle intervention for the management of overweight and obesity. It is characterized by a restriction of both calories and carbohydrates, while assuring the adequate proteins, fats and micronutrients intake. Significant results in terms of excess body weight loss have been reported and this strategy considered also in the preoperative settings. Improvements in hypertension, type 2 diabetes and dyslipidemia follows. EVIDENCE ACQUISITION: PubMed and Google Scholar were searched for papers reporting data on VLCKD as a strategy for the management of overweight, obesity and related disorders in adults. EVIDENCE SYNTHESIS: Four main documents are available in the literature and were included in the present narrative review. CONCLUSIONS: The present review discusses available evidence and provides practical recommendations for the management of VLCKD.

Prevalence of the Absence of Cirrhosis in Subjects with NAFLD-Associated Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is most commonly considered as a complication of cirrhosis. However, an increasing number of HCC in subjects with non-alcoholic fatty liver disease (NAFLD) without cirrhosis is being reported. We conducted a meta-analysis to assess the prevalence of the absence of cirrhosis in NAFLD-associated HCC. METHODS: Four databases were searched until March 2021 (CRD42021242969). The original articles included were those reporting data on the presence or absence of cirrhosis among at least 50 subjects with NAFLD-associated HCC. The number of subjects with absent cirrhosis in each study was extracted. For statistical pooling of data, a random-effects model was used. Subgroup analyses according to the continent, target condition and reference standard for the diagnosis of cirrhosis were conducted. RESULTS: Thirty studies were included, evaluating 13,371 subjects with NAFLD-associated HCC. The overall prevalence of cases without cirrhosis was 37% (95%CI 28 to 46). A higher prevalence was reported in Asia versus Europe, North America and South America (45, 36, 37 and 22%, respectively) as well as in studies adopting histology only as the reference standard for the diagnosis of cirrhosis versus histology and other modalities (e.g., radiology, endoscopy, biochemistry or overt clinical findings) (53 and 27%, respectively). No difference was found between studies including subjects with non-alcoholic steatohepatitis (NASH) only, versus NAFLD with or without NASH (p = 0.385). One in three subjects with NAFLD-associated HCC presented without cirrhosis. This should be reflected in future guidelines and surveillance programs adapted to allow for the early detection of these cancers too.

Modified Technique for Wirsung-Pancreatogastric Anastomosis after Pancreatoduodenectomy: A Single Center Experience and Systematic Review of the Literature.

BACKGROUND: The mortality rate following pancreaticoduodenectomy (PD) has been decreasing over the past few years; nonetheless, the morbidity rate remains elevated. The most common complications after PD are post-operative pancreatic fistula (POPF) and delayed gastric emptying (DGE) syndrome. The issue as to which is the best reconstruction method for the treatment of the pancreatic remnant after PD is still a matter of debate. The aim of this study was to retrospectively analyze the morbidity rate in 100 consecutive PD reconstructed with Wirsung-Pancreato-Gastro-Anastomosis (WPGA), performed by a single surgeon applying a personal modification of the pancreatic reconstruction technique. METHODS: During an 8-year period (May 2012 to March 2020), 100 consecutive patients underwent PD reconstructed with WPGA. The series included 57 males and 43 females (M/F 1.32), with a mean age of 68 (range 41-86) years. The 90-day morbidity and mortality were retrospectively analyzed. Additionally, a systematic review was conducted, comparing our technique with the existing literature on the topic. RESULTS: We observed eight cases of clinically relevant POPF (8%), three cases of "primary" DGE (3%) and four patients suffering "secondary" DGE. The surgical morbidity and mortality rate were 26% and 6%, respectively. The median hospital stay was 13.6 days. The systematic review of the literature confirmed the originality of our modified technique for Wirsung-Pancreato-Gastro-Anastomosis. CONCLUSIONS: Our modified double-layer WPGA is associated with a very low incidence of POPF and DGE. Also, the technique avoids the risk of acute hemorrhage of the pancreatic parenchyma.

Proton Pump Inhibitors and Fractures in Adults: A Critical Appraisal and Review of the Literature.

Despite the large number of patients worldwide being on proton pump inhibitors (PPIs) for acid-related gastrointestinal disorders, uncertainty remains over their long-term safety. Particularly, the potential side effects of these drugs on bone health have been evaluated in the last years. The purpose of our narrative review is to gather and discuss results of clinical studies focusing on the interactions between PPIs and fracture risk. Data generated mainly from nested case-control studies and meta-analysis suggest that long-term/high-dose PPIs users are characterized by an increased risk of fragility fractures, mainly hip fractures. However, in these studies, the PPIs-induced bone impairment is often not adjusted for different confounding variables that could potentially affect bone health, and exposure to PPIs was reported using medical prescriptions without adherence evaluation. The mechanisms of the PPI-related bone damage are still unclear, but impaired micronutrients absorption, hypergastrinemia, and increased secretion of histamine may play a role. Clinicians should pay attention when prescribing PPIs to subjects with a preexistent high risk of fractures and consider antiosteoporotic drugs to manage this additive effect on the bone. However, further studies are needed to clarify PPIs action on the bone.

Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy for Remission of Type 2 Diabetes.

CONTEXT: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the bariatric procedures most commonly used for the management of obesity. Whether one or the other is associated with a higher chance of remission of type 2 diabetes (T2D) is unclear. OBJECTIVE: This work aims to compare the efficacy of RYGB and SG for T2D remission at 1, 3, and 5 years after surgery. DATA SOURCES: Four databases were searched until January 2020. STUDY SELECTION: Randomized controlled studies with at least 12 months of follow-up of patients with T2D allocated to RYGB or SG were selected. DATA EXTRACTION: To ensure uniformity, broad and narrow criteria for T2D remission were defined. The number of patients achieving remission of T2D at each assessment was extracted. Data were pooled using a random-effects model. DATA SYNTHESIS: Ten studies were included, evaluating 778 patients. The overall prevalence of achievement of broad and narrow criteria for T2D remission was 73% and 53% at the 1-year, 60% and 48% at the 3-year, and 51% and 43% at the 5-year assessment. Compared to SG, RYGB was associated with a higher chance of achieving broad and narrow criteria for remission at 1 year after surgery (risk ratio [RR] = 1.34 vs RR = 1.22) and broad criteria for remission at 5 years (RR = 1.18). No other differences were found. CONCLUSIONS: The present meta-analysis suggests a more favorable effect of RYGB than SG on achieving T2D remission in the short-term only, although the evidence currently available does not clarify whether differences in this outcome are confirmed long term or fade thereafter.

A family history of type 2 diabetes as a predictor of fatty liver disease in diabetes-free individuals with excessive body weight.

Comprehensive screening for non-alcoholic fatty liver disease (NAFLD) may help prompt clinical management of fatty liver disease. A family history, especially of diabetes, has been little studied as a predictor for NAFLD. We characterized the cross-sectional relationship between a family history of type 2 diabetes (FHT2D) and NAFLD probability in 1185 diabetes-free Apulian (Southern-Italy) subjects aged > 20 years with overweight or obesity not receiving any drug or supplementation. Clinical data and routine biochemistry were analysed. NAFLD probability was defined using the fatty liver index (FLI). A first-degree FHT2D was assessed by interviewing subjects and assigning a score of 0, 1, or 2 if none, only one, or both parents were affected by type 2 diabetes mellitus (T2DM). Our study population featured most females (70.9%, N = 840), and 48.4% (N = 574) of the sample had first-degree FHT2D. After dividing the sample by a FHT2D, we found a higher BMI, Waist Circumference (WC), and diastolic blood pressure shared by FHT2D subjects; they also showed altered key markers of glucose homeostasis, higher triglyceride levels, and worse liver function. FLI scores were significantly lower in subjects without a first-degree FHT2D. After running logistic regression models, a FHT2D was significantly associated with the NAFLD probability, even adjusting for major confounders and stratifying by age (under and over 40 years of age). A FHT2D led to an almost twofold higher probability of NAFLD, regardless of confounding factors (OR 2.17, 95% CI 1.63 to 2.89). A first-degree FHT2D acts as an independent determinant of NAFLD in excess weight phenotypes, regardless of the age group (younger or older than 40 years). A NAFLD risk assessment within multidimensional screening might be useful in excess weight subjects reporting FHT2D even in the absence of diabetes.