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.

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.

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.

Liver Fibrosis and 8-Year All-Cause Mortality Trajectories in the Aging Cohort of the Salus in Apulia Study.

Age is a major contributor to the liver fibrosis rate and its adverse health-related outcomes, including mortality, but older populations are still under-explored. We investigated multimorbidity and inflammatory biomarkers in relation to the increasing liver fibrosis risk to delineate 8-year all-cause mortality trajectories in 1929 older adults from the population-based Salus in Apulia Study. Liver fibrosis risk was assumed using the fibrosis-4 (FIB-4) score, assigned to three liver fibrosis risk groups (low, intermediate, high). In the secondary analyses, the APRI score was also calculated to allow for comparisons. Male subjects (prevalence difference: -13.49, 95% confidence interval (CI): -18.96 to -8.03), a higher multimorbidity burden (effect size, ES: -0.14, 95% CI: -0.26 to -0.02), a higher prevalence of physical frailty (ES: 6.77, 95% CI: 0.07 to 13.47), and a more pronounced inflammatory pattern as indicated by tumor growth factor-α circulating levels (ES: -0.12, 95% CI: -0.23 to -0.01) were significantly more common in the highest-risk FIB-4 score group. Liver function characterized by lipid profile and platelet levels worsened with increasing FIB-4 risk score. The 8-year risk of death was nearly double in subjects in the highest-risk FIB-4 score group, even after controlling for possible confounders. Furthermore, a steeper mortality curve was clearly observed for FIB-4 scores as compared with the APRI scoring system with respect to liver fibrosis risk. In conclusion, using a scoring tool based on simple routine biomarkers to detect liver fibrosis risk may enhance biological knowledge of age-related outcomes of chronic liver disease and be helpful in the clinical setting to identify subjects at risk for adverse health-related outcomes, including mortality.

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.

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.

Non Alcoholic Fatty Liver Disease Is Positively Associated with Increased Glycated Haemoglobin Levels in Subjects without Diabetes.

Screening for non-alcoholic fatty liver disease (NAFLD) is key step for primary management of fatty liver in the clinical setting. Excess weight subjects carry a greater metabolic risk even before exhibiting pathological patterns, including diabetes. We characterized the cross-sectional relationship between routine circulating biomarkers and NAFLD in a large sample of diabetes-free subjects with overweight or obesity, to elucidate any independent relationship. A population sample of 1232 consecutive subjects with a body mass index of at least 25 kg/m2, not receiving any drug or supplemental therapy, was studied. Clinical data and routine biochemistry were analyzed. NAFLD was defined using the validated fatty liver index (FLI), classifying subjects with a score ≥ 60% as at high risk. Due to extreme skewing of variables of interest, resampling matching for age and sex was performed. Our study population was characterized by a majority of females (69.90%) and a prevalence of NAFLD in males (88.90%). As a first step, propensity score matching was explicitly performed to balance the two groups according to the FLI cut-off. Based on the resulting statistical trajectories, corroborated even after data matching, we built two logistic regression models on the matched population (N = 732) to verify any independent association. We found that each unit increase of FT3 implicated a 50% increased risk of NAFLD (OR 1.506, 95%CI 1.064 to 2.131). When including glycated haemoglobin (HbA1c) in the model, free-triiodothyronine (FT3) lost significance (OR 1.557, 95%CI 0.784 to 3.089) while each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold (OR 2.32, 95%CI 1.193 to 4.512). Glucose metabolism dominates a key pathway along the hazard trajectories of NAFLD, turned out to be key biomarker in monitoring the risk of fatty liver in diabetes-free overweight subjects. Each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold, in our study.

Performance of Fatty Liver Index in Identifying Non-Alcoholic Fatty Liver Disease in Population Studies. A Meta-Analysis.

BACKGROUND: Fatty liver index (FLI) is a non-invasive tool used to stratify the risk of non-alcoholic fatty liver disease (NAFLD) in population studies; whether it can be used to exclude or diagnose this disorder is unclear. We conducted a meta-analysis to assess the prevalence of NAFLD in each FLI class and the performance of FLI in detecting NAFLD. METHODS: Four databases were searched until January 2021 (CRD42021231367). Original articles included were those reporting the performance of FLI and adopting ultrasound, computed tomography, or magnetic resonance as a reference standard. The numbers of subjects with NAFLD in FLI classes <30, 30-60, and ≥60, and the numbers of subjects classified as true/false positive/negative when adopting 30 and 60 as cut-offs were extracted. A random-effects model was used for pooling data. RESULTS: Ten studies were included, evaluating 27,221 subjects without secondary causes of fatty liver disease. The prevalence of NAFLD in the three FLI classes was 14%, 42%, and 67%. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for positive results, likelihood ratio for negative results, and diagnostic odds ratio were 81%, 65%, 53%, 84%, 2.3, 0.3, and 7.8 for the lower cut-off and 44%, 90%, 67%, 76%, 4.3, 0.6, and 7.3 for the higher cut-off, respectively. A similar performance was generally found in studies adopting ultrasound versus other imaging modalities. CONCLUSIONS: FLI showed an adequate performance in stratifying the risk of NAFLD. However, it showed only weak evidence of a discriminatory performance in excluding or diagnosing this disorder.

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.

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.

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.

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.

Nutritional domains in frailty tools: Working towards an operational definition of nutritional frailty.

Different methods have been proposed for the assessment of the nutritional status in frailty phenotypes. In the present narrative review article, we have summarized the number and specifications of nutritional items in existing frailty tools, in order to develop a possible means of assessment and operational definition of the nutritional frailty phenotype. In six different databases until December 2019, we searched for original articles regarding frailty tools (i.e., scales, indexes, scores, questionnaires, instruments, evaluations, screening, indicators), analyzing each tool regarding nutritional items. We identified 160 articles describing 71 frailty tools. Among the selected frailty tools, 54 were community-based (70 %), 17 hospital-based (22 %), 4 validated in long-term care institutions for older adults (LTCIOA) (5.1 %) and 2 validated in both community- and hospital-based settings, including LTCIOA (2.5 %). Fifty-two of these tools (73 %) included at least one nutritional item. Twenty-two (42 %) reported two or more nutritional items. The items were grouped in the following categories: A) anthropometric measurements, B) laboratory measurements, and C) other nutritional-related measurements. Anthropometric measurements stood out compared to all other items. Nutritional items are included in the majority of frailty tools, strengthening the concept that they may have a direct implication on an increased risk of adverse health-related outcomes in frail subjects. This supports the development of the concept of nutritional frailty as an independent frailty phenotype. Subsequent steps will be to assess the contribution of each nutritional item to a possible operational definition of nutritional frailty and define the items that may best identify this new frailty phenotype.

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.

Efficacy and safety of patient-led versus physician-led titration of basal insulin in patients with uncontrolled type 2 diabetes: a meta-analysis of randomized controlled trials.

INTRODUCTION: Insulin is the most effective antihyperglycemic treatment and basal insulin is the preferred initial formulation in patients with type 2 diabetes. However, its effects are dose-dependent, so adequate titration is necessary to reach targets. We performed a meta-analysis to compare the efficacy and safety of patient-led versus physician-led titration of basal insulin in patients with uncontrolled type 2 diabetes. RESEARCH DESIGN AND METHODS: Four databases were searched from database inception through March 2020. Randomized controlled studies with at least 12 weeks of follow-up of patients with type 2 diabetes allocated to patient-led versus physician-led titration of basal insulin were selected. Data on glycemic endpoints (hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), hypoglycemia) and other outcomes (insulin dose, body weight, patient-reported outcomes, adverse events, rescue medication, discontinuation) were extracted. Data were pooled using a random-effects model. RESULTS: Six studies evaluating 12 409 patients were finally included. Compared with the physician-led performance, patient-led titration was associated with a statistically significant higher basal insulin dose (+6 IU/day), leading to benefits on HbA1c (-0.1%) and FPG (-5 mg/dL), despite a higher risk of any level hypoglycemia (relative risk=1.1) and a slight increase in body weight (+0.2 kg). No difference was found for the other outcomes. CONCLUSIONS: The present study showed that patient-led titration of basal insulin was not inferior to physician-led titration in patients with uncontrolled type 2 diabetes. Therefore, diabetes self-management education and support programs on basal insulin should be widely adopted in clinical practice and patients provided with tools to self-adjust their dose when necessary.

Performance of EU-TIRADS in malignancy risk stratification of thyroid nodules: a meta-analysis.

OBJECTIVE: Several thyroid imaging reporting and data systems (TIRADS) have been proposed to stratify the malignancy risk of thyroid nodule by ultrasound. The TIRADS by the European Thyroid Association, namely EU-TIRADS, was the last one to be published. DESIGN: We conducted a meta-analysis to assess the prevalence of malignancy in each EU-TIRADS class and the performance of EU-TIRADS class 5 vs 2, 3 and 4 in detecting malignant lesions. METHODS: Four databases were searched until December 2019. Original articles reporting the performance of EU-TIRADS and adopting histology as reference standard were included. The number of malignant nodules in each class and the number of nodules classified as true/false positive/negative were extracted. A random-effects model was used for pooling data. RESULTS: Seven studies were included, evaluating 5672 thyroid nodules. The prevalence of malignancy in each EU-TIRADS class was 0.5% (95% CI: 0.0-1.3), 5.9% (95% CI: 2.6-9.2), 21.4% (95% CI: 11.1-31.7), and 76.1% (95% CI: 63.7-88.5). Sensitivity, specificity, PPV, NPV, LR+, LR- and DOR of EU-TIRADS class 5 were 83.5% (95% CI: 74.5-89.8), 84.3% (95% CI: 66.2-93.7), 76.1% (95% CI: 63.7-88.5), 85.4% (95% CI: 79.1-91.8), 4.9 (95% CI: 2.9-8.2), 0.2 (95% CI: 0.1-0.3), and 24.5 (95% CI: 11.7-51.0), respectively. A further improved performance was found after excluding two studies because of limited sample size and low prevalence of malignancy in class 5. CONCLUSIONS: A limited number of studies generally conducted using a retrospective design was found. Acknowledging this limitation, the performance of EU-TIRADS in stratifying the risk of thyroid nodules was high. Also, EU-TIRADS class 5 showed moderate evidence of detecting malignant lesions.

Efficacy and safety of flash glucose monitoring in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis.

INTRODUCTION: Flash glucose monitoring (FGM) is a factory-calibrated sensor-based technology for the measurement of interstitial glucose. We performed a systematic review and meta-analysis to assess its efficacy and safety in patients with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: PubMed, CENTRAL, Scopus and Web of Science were searched in July 2019. Twelve studies with a follow-up longer than 8 weeks, evaluating 2173 patients on prandial insulin, multiple daily insulin injections or continuous subcutaneous insulin infusion were included. The following data were extracted: HbA1c, time in range, time above 180 mg/dL, time below 70 mg/dL, frequency of hypoglycemic events, number of self-monitoring of blood glucose (SMBG) measurements, total daily insulin dose, patient-reported outcomes, adverse events, and discontinuation rate. A comparison with SMBG was conducted. RESULTS: FGM use was associated with a reduction in HbA1c (-0.26% (-3 mmol/mol); p=0.002) from baseline to the last available follow-up, which correlated with HbA1c levels at baseline (-0.4% (-4 mmol/mol) for each 1.0% (11 mmol/mol) of HbA1c above 7.2% (55 mmol/mol)). Also, a decrease in time below 70 mg/dL was found (-0.60 hours/day; p=0.04). Favorable findings in patient-reported outcomes and no device-related serious adverse events were reported. When compared with SMBG, FGM was characterized by no statistically different change in HbA1c (p=0.09), with lower number of SMBG measurements per day (-3.76 n/day; p<0.001) and risk of discontinuation (relative risk=0.42; p=0.001). A limited number of studies, with a heterogeneous design and usually with a short-term follow-up and without specific training, were found. CONCLUSIONS: The present review provides evidence for the use of FGM as an effective strategy for the management of diabetes.