Short-term glucose variability as a determinant of the healing rate of diabetic foot ulcer: A retrospective study.

BACKGROUND: The aim of this study was to describe the clinical characteristics of people with diabetic foot ulcer (DFU) according to glucose variability (GV) and to investigate the relationship between GV and DFU outcome in a population with type 2 diabetes (T2D) and DFU. METHODS: This is a retrospective study of 300 individuals aged 64.3 years (181 males) treated for DFU in a tertiary-care center with a regular follow-up for 6 months. Laboratory measurements and clinical assessments were collected at baseline. According to the coefficient of variation (CV) cut-off (≥36%), people were divided into two groups (low and high GV). RESULTS: Compared with low GV group (n = 245), high GV group (n = 55) had significant longer duration of diabetes [low vs high GV, mean ± Standard Deviation (SD), 17.8 ± 11.8 vs 22.4 ± 10.8, P = 0.012], higher levels of glycated haemoglobin [median (IQR), 7.4 (6.6, 8.8) vs 8.2 (7.0, 9.6), P = 0.010] and urinary albumin excretion [25.2 (11.9, 77.0) vs 48.0 (23.2, 106.0), P = 0.031]. Moreover, 10 days self-monitoring of blood glucose-derived glycemic metrics were significantly different between groups. No differences among clinical features were found. The multiple logistic regression analysis identified CV and SD as negative predictors of healing. CONCLUSIONS: In a population of people with T2D and DFU treated in a tertiary-care center, individuals with high GV had a 3-fold higher risk of healing failure, as compared with those with low GV. CV and SD were related to poor healing within 6 months follow-up.

Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease: The STARDUST Randomized Clinical Trial.

Importance: Peripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high cardiovascular risk. Objective: To examine the effect of liraglutide on peripheral perfusion measured as peripheral transcutaneous oxygen pressure (TcPo2) in individuals with type 2 diabetes and PAD. Design, Setting, and Participants: This open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022, with a final follow-up on December 30, 2022, at University of Campania "Luigi Vanvitelli," Naples, Italy. Fifty-five individuals with type 2 diabetes, PAD, and TcPo2 between 30 and 49 mm Hg were included. Interventions: Patients were randomized to receive 1.8 mg of subcutaneous liraglutide or conventional treatment of cardiovascular risk factors (control group) for 6 months. Main Outcomes and Measures: Coprimary outcomes were the change from baseline of peripheral perfusion between groups and the comparison of the proportion of individuals who reached 10% increase of TcPo2 from baseline in each group. Results: Fifty-five participants (mean [SD] age, 67.5 [8.5] years; 43 [78%] male) were randomized (27 to the liraglutide group and 28 to the control group) and analyzed. Participants had a median (IQR) hemoglobin A1c level of 6.9% (6.5%-7.8%) and a mean (SD) TcPo2 of 40.3 (5.7) mm Hg. Transcutaneous Po2 increased over time in both groups, with significant differences favoring the liraglutide group after 6 months (estimated treatment difference, 11.2 mm Hg; 95% CI, 8.0-14.5 mm Hg; P < .001). The 10% increase of TcPo2 occurred in 24 participants (89%) in the liraglutide group and 13 (46%) in the control group (relative risk, 1.91; 95% CI, 1.26-2.90; P < .001). Compared with the control group, individuals in the liraglutide group had a significant reduction of C-reactive protein (-0.4 mg/dL; 95% CI, -0.7 to -0.07 mg/dL; P = .02), urinary albumin to creatinine ratio (-119.4 mg/g; 95% CI, -195.0 to -43.8 mg/g; P = .003), and improvement of 6-minute walking distance (25.1 m; 95% CI, 21.8-28.3 m; P < .001). Conclusions and Relevance: In this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcPo2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes. Trial Registration: ClinicalTrials.gov Identifier: NCT04881110.

Two years with GIOIA 'Effects of gliflozins and gliptins on markers of cardiovascular damage in type 2 diabetes': A prospective, multicentre, quasi-experimental study on sodium-glucose cotransporter 2 and dipeptidyl peptidase-4 inhibitors in diabetes clinical practice.

AIM: To assess and compare the metabolic and vascular effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in the clinical practice of patients with type 2 diabetes in Italy. MATERIALS AND METHODS: GIOIA is a 2-year prospective, multicentre, quasi-experimental study that enrolled patients with type 2 diabetes initiating SGLT-2i or DPP-4i for inadequate glycaemic control [glycated haemoglobin (HbA1c) >7%] between March 2018 and March 2021. The primary endpoints were changes in markers of organ damage [carotid intima-media thickness (CIMT), albuminuria, myocardial function] and HbA1c from baseline to year 2. RESULTS: In total, 1150 patients were enrolled in the study (SGLT-2i n = 580, DPP-4i n = 570). Patients initiated on SGLT-2i were younger (about 6 years) and heavier (about 11 kg), had higher HbA1c level (1% more), more albuminuria and cardiovascular events (16% more) than patients initiated on DPP-4i. CIMT and echocardiographic parameters were not significantly different. Propensity score matching yielded two groups, each consisting of 155 patients with diabetes with similar baseline characteristics. Despite a significant similar reduction in HbA1c levels in both groups (-0.8%), more patients on SGLT-2i had regression of CIMT and albuminuria (22% and 10%, respectively, p < .001 vs. DPP-4i); more patients on DPP-4i had progression of CIMT and albuminuria (23% and 28%, respectively, p < .001 vs. SGLT-2i). Left ventricular ejection fraction improved slightly (3%, p = .043) on SGLT-2i only. CONCLUSIONS: In a real-world setting, both SGLT-2i and DPP-4i improve glycaemic control persisting after 2 years of treatment, with a robust effect on both CIMT and albuminuria regression for SGLT-2i as compared with DPP-4i in the propensity score matching.

Telemedicine for type 2 diabetes during COVID-19 pandemic: experience from a tertiary diabetes center.

BACKGROUND: Telemedicine was largely employed during COVID-19 pandemic to guarantee continuity of care in a period of dramatic reduction of face-to-face visits. The aim of this study was to describe the clinical characteristics of a cohort of patients with type 2 diabetes followed by tele-visits and to evaluate the changes in the glyco-metabolic control during a 12-month follow-up. METHODS: This retrospective observational study included 136 adults aged >18 years with at least three tele-visits over a 12-month follow-up period, in a Diabetes Center of the Southern Italy, from April 2020 to March 2022. Data related to glycemic and lipid profile, therapy, presence of micro or macrovascular complications, and other clinical features were extracted at three time points, at first visit (T0), after 6 months (T1) and after 12 months (T2). RESULTS: Mean diabetes duration and median HbA1c values were 11.6 years and 7.0%, respectively. Thirty-eight participants (27.9%) presented macro- or microvascular complications. Glycemic control remained stable over time, without clinically significant changes of HbA1c (T0 vs. T1 vs. T2, median [IQR], 7.0 [6.2-7.3], 6.6 [6.0-7.5], 6.9 [6.2-7.5], P=0.095) and fasting glucose. Lipid profile slightly improved, although without significant clinical change. Glucose lowering therapy was modified in 84 patients (61.8%) and remained unchanged in 52 patients (38.2%) during the follow-up. No participant in the study developed any complications during the 12-month follow-up. CONCLUSIONS: People with type 2 diabetes followed by telemedicine were adults with fair glucose control generally free from chronic complications, whose diabetes control did not worsen during a 12-month follow-up.

Psychometric properties of health-related quality of life instruments used in survivors of critical illness: a systematic review.

BACKGROUND AND OBJECTIVES: Health-related quality of life (HRQoL) is a patient-reported measure of health status. However, research on the psychometric properties of HRQoL instruments used post-critical care is less common. We conducted a systematic review assessing the psychometric properties of HRQoL instruments used in adult survivors following critical illness. METHODS: Three databases were systematically searched between 1990 and June 2022. Screening articles for eligibility, we selected either development studies for new tools or studies that evaluated psychometric properties, and whose target population represented adult survivors following critical illness. Methodological quality was assessed using the COnsensus-Based Standards for the selection of health Measurement INstruments (COSMIN) checklist. The results of each psychometric property were then assessed for criteria of good psychometric properties (sufficient, insufficient or indeterminate) and qualitatively summarised. Finally, we graded the quality of the evidence using a modified GRADE approach. RESULTS: We retrieved 13 eligible studies from 2,983 records identifying 10 HRQoL instruments used post-critical illness. While high-quality evidence for the considered PROMs was limited primarily due to risk of bias, seven instruments demonstrated sufficient levels of reliability, four instruments presented sufficient hypothesis testing, and two instruments showed sufficient responsiveness. Except the Short Form-36, evidence for psychometric properties of other individual measures was limited to a few studies. CONCLUSION: There was limited evidence demonstrated for the psychometric properties of the included PROMs evaluating HRQoL. Further research is warranted to evaluate the psychometric properties of HRQoL measures, strengthening the evidence for administering these instruments in survivors following critical illness.

BEYOND 2 years: durability of metabolic benefits by simplification of complex insulin regimens in type 2 diabetes.

PURPOSE: To assess the magnitude and durability of the metabolic benefits by simplification of complex insulin treatments in patients with type 2 diabetes inadequately controlled by a full basal-bolus insulin regimen. Herein we report the results of the scheduled 2-year extension of the BEYOND trial. METHODS: Originally, 305 participants with inadequate glycemic control (HbA1c > 7.5%) were randomly assigned to intensification of basal-bolus insulin regimen (n = 101), to a fixed-ratio combination (basal insulin + GLP-1RA, n = 102), or to an association of basal insulin plus an SGLT-2 inhibitor (gliflo-combo, n = 102). The primary efficacy outcome was change from baseline in HbA1c at 24 months assessed by an intention-to-treat analysis. A per-protocol analysis was also performed. RESULTS: Fifty-five percent of patients completed the study in the two comparison arms. Compared with patients randomized to basal-bolus, patients of the other groups experienced non statistically different reductions in HbA1c level according to either an intention-to-treat analysis (-0.8 ± 1.1%, -0.7 ± 1.1%, and -1.3 ± 1.1%, mean ± SD, fixed-ratio, gliflo-combo and basal bolus, respectively) or per-protocol analysis (-1.2 ± 1.0%, -1.2 ± 1.1%, and -1.3 ± 1.0%, respectively). The final HbA1c level (per protocol) was 7.2 ± 0.8%, 7.3 ± 0.9%, and 7.5 ± 0.9%, respectively (P = NS). Treatment satisfaction (DTSQ) increased in both exchange groups, whereas the proportion of patients with hypoglycemia was lower. CONCLUSION: Simplification of complex insulin regimen may be a durable option in at least one-half of patients with type 2 diabetes. CLINICAL TRIAL REGISTRATION: Clinical trial registration no. NCT04196231, clinicaltrials.gov.

Glucose control during breakthrough SARS-CoV-2 infections in vaccinated patients with type 1 diabetes.

AIMS: This study aims at evaluating the trend of glycemic control metrics during the infection of SARS-CoV-2 in individuals with Type 1 Diabetes (T1D) using a Continuous Glucose Monitoring (CGM) system and vaccinated against COVID-19. MATERIALS AND METHODS: This is a retrospective study of T1D subjects who got a breakthrough SARS-CoV-2 infection between November 2021 and February 2022. Data of glycemic control of CGM-derived metrics were compared 14 days before COVID-19 (Time 1), 14 days during COVID-19 (Time 2) and 14 days after COVID-19 (Time 3). RESULTS: A total of 106 patients with T1D and breakthrough SARS-CoV-2 infection was included in the analysis. A significant reduction of GMI [%, 7.41 ± 1.60 vs 7.52 ± 1.63, P = 0.006)] and increase of TIR [%, 54.6 ± 20.4 vs 52.1 ± 19.7, P = 0.026] were observed at Time 3 as compared with Time 2. There was a significant reduction of SD (P < 0.001) and CV (P < 0.001) at Time 3 and Time 2 as compared with Time 1, associated with significant changes of mean glucose levels, TBR level 1 and total daily insulin doses. CONCLUSIONS: Breakthrough SARS-CoV-2 infection did not worsen glycemic control in vaccinated people with T1D.

Prediction of classical versus non classical papillary thyroid carcinoma subtypes from cytology of nodules classified according to TIRADS.

PURPOSE: Our purposes were: 1) to estimate the prediction performance (PP) of cytology in identifying papillary thyroid carcinoma (PTC) subtypes; 2) to explore how the PTC subtypes distribute among the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) categories. METHODS: Nodules were included if both the histology with the PTC subtype report and the cytology report with the possible PTC subtype were available. The PP was calculated by making the proportion of True positives/False positives+false negatives. RESULTS: 309 cytologically "suspicious for malignancy" and "malignant" thyroid nodules with PTC histology were evaluated. ACR TI-RADS categorization for classical PTC was significantly different from non-classical PTC (p-value 0.02). For the whole cohort the PP of cytologically classical cases was 0.74, while that of cytologically non classical cases was 0.41. ACR TI-RADS categorization was not significantly different for aggressive vs non-aggressive PTC subtypes (p-value 0.1). When considering only aggressive or non-aggressive PTC subtypes, the PP of cytologically classical cases was respectively 0.86 and 0.87, while that of cytologically non classical cases was respectively 0.27 and 0.22. The PP of cytologically classical cases was 0.73 and 0.79, respectively for macroPTCs and microPTCs, while that of cytologically non classical cases was 0.55 and 0.33, respectively for macroPTCs and microPTCs. CONCLUSION: Cytology examination reliably performed in predicting classical PTC versus non classical PTC subtypes. ACR TI-RADS categorization was significantly different among classical PTC versus non classical PTC subtypes.

An updated algorithm for an effective choice of continuous glucose monitoring for people with insulin-treated diabetes.

PURPOSE: Continuous Glucose Monitoring (CGM) is a key tool for insulin-treated people with diabetes (PwD). CGM devices include both real-time CGM (rtCGM) and intermittently scanned CGM (isCGM), which are associated with an improvement of glucose control and less hypoglycemia in clinical trials of people with type 1 and type 2 diabetes. METHODS: This is an expert position to update a previous algorithm on the most suitable choice of CGM for insulin-treated PwD in light of the recent evidence and clinical practice. RESULTS: We identified six different clinical scenarios, including type 1 diabetes, type 2 diabetes, pregnancy on intensive insulin therapy, regular physical exercise, new onset of diabetes, and frailty. The use of rtCGM or isCGM is suggested, on the basis of the predominant clinical issue, as suboptimal glucose control or disabling hypoglycemia, regardless of baseline HbA1c or individualized HbA1c target. CONCLUSION: The present algorithm may help to select the best CGM device based on patients' clinical characteristics, needs and clinical context, offering a further opportunity of a "tailored" therapy for people with insulin-treated diabetes.

Impact of Current Technology in Laparoscopic Adrenalectomy: 20 Years of Experience in the Treatment of 254 Consecutive Clinical Cases.

BACKGROUND: Laparoscopic adrenalectomy (LA), which avoids large abdomen incisions, is considered the gold standard technique for the treatment of benign small- and medium-size adrenal masses (<6 cm) and weighing < 100 g. A trascurable mortality and morbidity rate, short hospitalization and patient rapid recovery are the main advantages compared to traditional surgery. During the past decade, a new surgical technology has been developed that expedites a "clipless" adrenalectomy. Here, the authors analyze a clinical series of 254 consecutive patients who were affected by adrenal gland neoplasms and underwent LA by the transabdominal lateral approach over the two last decades. A literature review is also presented. METHODS: Preoperative, intraoperative and postoperative data from 254 patients who underwent LA between January 2003 and December 2022 were retrospectively collected and reviewed. Diagnosis was obtained on the basis of clinical examination, laboratory values and imaging techniques. Doxazosin was preoperatively administered in the case of pheochromocytoma (PCC) while spironolactone and potassium were employed to treat Conn's disease. The same surgeon (CG) performed all the LA and utilized the same laparoscopic transabdominal lateral approach. Different dissection tools-ultrasonic, bipolar or mixed scissors-and hemostatic agents were used during this period. The following results were obtained: 254 patients were included in the study; functioning tumors were diagnosed in 155 patients, 52 patients were affected by PCCs, 55 by Conn's disease, 48 by Cushing's disease. Surgery mean operative time was 137.33 min (range 100-180 min) during the learning curve adrenalectomies and 98.5 min (range 70-180) in subsequent procedures. Mean blood loss was respectively 160.2 mL (range 60-280) and 96.98 mL (range 50-280) in the first 30 procedures and the subsequent ones. Only three conversions (1.18%) to open surgery occurred. No mortality or postoperative major complications were observed, while minor complications occurred in 19 patients (3.54%). In 153 out of 155 functioning neoplasms, LA was effective in the normalization of the endocrine profile. According to our experience, a learning curve consisting of 30 cases was identified. In fact, a lower operative time and a lower complication rate was reported following 30 LA. CONCLUSIONS: LA is a safe procedure, even for masses larger than 6 cm and PCCs. Undoubtedly, the development of surgical technology has made it possible reducing operative times, performing a "clipless" adrenalectomy and extending the indications in the treatment of more complex patients. A multidisciplinary team, in referral high-volume centers, is recommended in the management of adrenal pathology. A 30-procedure learning curve is necessary to improve surgical outcomes.

Signs of a Glucose- and Insulin-Independent Gut-Bone Axis and Aberrant Bone Homeostasis in Type 1 Diabetes.

CONTEXT: Gut hormones seem to play an important role in postprandial bone turnover, which also may be affected by postprandial plasma glucose excursions and insulin secretion. OBJECTIVE: To investigate the effect of an oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion (IIGI) on bone resorption and formation markers in individuals with type 1 diabetes and healthy controls. METHODS: This observational case-control study, conducted at the Center for Clinical Metabolic Research, Gentofte Hospital, Hellerup, Denmark, included 9 individuals with C-peptide negative type 1 diabetes and 8 healthy controls matched for gender, age, and body mass index. Subjects underwent an OGTT and a subsequent IIGI. We analyzed changes in bone resorption assessed by measurements of carboxy-terminal type I collagen crosslinks (CTX) and in bone formation as assessed by procollagen type I N-terminal propeptide (PINP) concentrations. RESULTS: Baseline CTX and PINP levels were similar in the 2 groups. Both groups exhibited significantly greater suppression of CTX during OGTT than IIGI. PINP levels were unaffected by OGTT and IIGI, respectively, in healthy controls. Participants with type 1 diabetes displayed impaired suppression of CTX-assessed bone resorption and inappropriate suppression of PINP-assessed bone formation during OGTT. CONCLUSION: Our data suggest the existence of a gut-bone axis reducing bone resorption in response to oral glucose independently of plasma glucose excursions and insulin secretion. Subjects with type 1 diabetes showed impaired suppression of bone resorption and reduced bone formation during OGTT, which may allude to the reduced bone mineral density and increased fracture risk characterizing these individuals.

Circulating levels of endothelial progenitor cells are associated with better cognitive function in older adults with glucagon-like peptide 1 receptor agonist-treated type 2 diabetes.

AIMS: To evaluate cognitive function in subjects with type 2 diabetes (T2D) treated with glucagon-like peptide 1 receptor agonist (GLP-1RA) plus metformin or metformin alone and its association with endothelial progenitor cells (EPCs). METHODS: Adults with T2D treated with GLP-1RA plus metformin (GLP-1RA + MET) or MET alone for at least 12 months were included. Montreal Cognitive Assessment test (MoCA), Mini-Mental State Examination (MMSE), Mini Nutritional Assessment (MNA) and disability tests were administered. Circulating levels of seven EPCs phenotypes were measured by flow cytometry. RESULTS: A total of 154 elderly patients were included, of whom 78 in GLP-1RA + MET group and 76 in MET group. The GLP-1RA + MET group showed better cognitive function as indicated by a significant higher MoCA and MMSE scores, and higher levels of CD34+ CD133+, CD133+ KDR+, and CD34+ CD133+ KDR+ as compared with MET group. The number of CD34+ CD133+ KDR+ cells was an independent predictor of higher MoCA, MMSE and MNA scores. CONCLUSIONS: People with T2D on GLP-1RA + MET treatment had better cognitive function and higher circulating levels of EPCs as compared with those on MET alone warranting further studies to understand the interrelationship between EPCs, GLP-RA treatment and cognitive health.

Biochemical predictors of diabetic foot osteomyelitis: A potential diagnostic role for parathormone.

AIMS: The aims of this study were to evaluate parathormone (PTH) levels in people with diabetic foot ulcers (DFU) and investigate the relationship between PTH levels and osteomyelitis (OM) in this population. MATERIALS AND METHODS: Eighty-eight patients were admitted for DFU in a tertiary-care centre from October 2021 to May 2022. OM was diagnosed by clinical, laboratory, and radiological evaluations. Laboratory measurements and clinical parameters were collected from medical records. Participants in the study were divided into two groups according to the diagnosis of OM (patients with OM, group 1 [n = 54] and patients without OM, group 2 [n = 34]). RESULTS: Compared with group 2, patients in group 1 were younger and had a longer duration of diabetes. Erythrocyte sedimentation rate and fibrinogen were significantly higher in group 1 compared with group 2. PTH levels were significantly lower (group 1 vs. group 2, median [interquartile range] 16.2 (11.6, 31.0) vs. 23.7 (17.0, 38.1), p = 0.008) and alkaline phosphatase was significantly higher (97.0 (79.0, 112.0) vs. 88.0 (63.0, 107.0), p = 0.031) in group 1. In multiple linear regression analysis, the only independent predictors of PTH concentrations were alkaline phosphatase levels (ß-coefficient 0.441, p < 0.001) and the presence of OM (ß-coefficient -0.290, p = 0.038). CONCLUSIONS: In a population of patients with diabetes and OM admitted to a tertiary university centre, PTH levels were lower as compared with diabetic individuals without OM. The OM and alkaline phosphatase levels were independent predictors of PTH levels in this selected population.

Neuroimmunoendocrinology of SARS-CoV 2 Infection.

This review is aimed at illustrating and discussing the neuroimmune endocrinological aspects of the SARS-CoV-2 infection in light of the studies on this topic that have so far appeared in the literature. The most characteristic findings and pending controversies were derived by PubMed and Scopus databases. We included original and observational studies, reviews, meta-analysis, and case reports. The entry of the coronavirus into susceptible cells is allowed by the interaction with an ecto-enzyme located on human cells, the angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 also targets the central nervous system (CNS), including hypothalamic-pituitary structures, as their tissues express ACE2, and ACE2 mRNA expression in hypothalamus and pituitary gland cells has been confirmed in an autoptic study on patients who died of COVID 19. SARS-CoV-2 infection may cause central endocrine disorders in acute phase and in post-COVID period, particularly due to the effects of this virus at CNS level involving the hypothalamic-pituitary axis. The aggression to the hypothalamus-pituitary region may also elicit an autoimmune process involving this axis, responsible consequently for functional disorders of the satellite glands. Adrenal, thyroid and gonadal dysfunctions, as well as pituitary alterations involving GH and prolactin secretions, have so far been reported. However, the extent to which COVID-19 contributes to short- and long-term effects of infection to the endocrine system is currently being discussed and deserves further detailed research.

Varicocele: An Endocrinological Perspective.

Varicocele affects 15% of male population but it is more frequently identified in patients searching medical care for infertility. The impact of varicocele on semen production and fertility is known, but the relationship between clinical varicocele and impaired hormonal production is not clear. In published literature there are some studies regarding hormonal alterations in patients with varicocele but no review in which all the hormonal findings are explained. The aim of this review is to evaluate, by most common search engine, what is known about hormonal alterations in varicocele-bearing patients, to verify if a cause-effect relationship is documented and to give a useful contribution to in clinical management of this kind of patients. We found contradictory results about hormonal status from literature. Some studies confirmed a decrease of testosterone levels and higher FSH and LH levels that normalize after varicocelectomy, others found lower than normal levels of dihydrotestosterone due to decreased activity of epididymal 5-α-reductase. Lower circulating Anti-Müllerian Hormone levels, accompanied by a decreased Inhibin-B level, were reported as indicators of the decreased Sertoli cells function in varicocele-bearing adult patients. The finding of higher basal 17-OH-progesterone concentrations in patients with varicocele was explained by some authors with a testicular C-17,20-lyase deficiency. There is no doubt that varicocele could led to hormonal alterations. This review proposes that the impaired free sexual steroid levels are the result of a slight, deep-rooted defect in the testes of a certain amount of men with varicocele but further multicentre, randomized controlled studies remain mandatory to better clarify the hormonal features of patients with varicocele and to assess the utility of hormonal evaluation for establishing the duration of varicocele and for better identifying patients who need surgical correction.

Repeat thyroid FNAC: Inter-observer agreement among high- and low-volume centers in Naples metropolitan area and correlation with the EU-TIRADS.

Our institution (University Hospital "L. Vanvitelli" - Naples, Italy) is a high-volume (HV) center in Naples metropolitan area and many patients are referred there to repeat thyroid fine-needle aspiration cytology (FNAC) after initial FNAC performed in low-volume institutions (LV). The aims of the study were to 1) examine the inter-observer agreement between HV and LV institutions according to the Italian thyroid cytology system, and 2) explore how the discordant FNAC reports were distributed in the European Thyroid Imaging and Reporting Data System (EU-TIRADS) categories. All consecutive cases of repeat FNAC performed at University Hospital "L. Vanvitelli" from January 2016 to December 2021 were retrospectively reviewed. Fleiss' kappa (κ) was used to assess the inter-observer agreement, and categorical variables were compared by chi-square testing. P < 0.05 was considered statistically significant. A total of 124 nodules from 124 adults (mean age 49 years; mean maximum diameter 19 mm) were evaluated. Initial FNAC reports at LV were: 4 (3.2%) TIR1c, 64 (51.6%) TIR2, 48 (38.7%) TIR3A, 8 (6.5%) TIR3B, 0 TIR4, 0 TIR5. The overall FNAC reports were significantly different between the LV and HV institutions. At repeated FNAC, cytological diagnosis was unchanged in 64 (51.6%) cases including TIR2 and TIR3A results. A downgraded FNAC diagnosis (i.e., TIR2 vs TIR3A, TIR2 vs TIR3B) was observed in 36 (29%) nodules. An upgraded FNAC diagnosis (i.e., TIR3B vs TIR2, TIR3B vs TIR3A, TIR4 vs TIR3A, TIR5 vs TIR2, TIR5 vs TIR3B) was recorded in 24 (19.4%) nodules. The weighted inter-observer agreement between LV and HV institutions was poor (κ=0.133). Changed FNAC results were significantly (p=0.0023) more frequent in nodules at intermediate/high-risk (i.e., EU-TIRADS 4/5) than in those at no/low risk (EU-TIRADS 2/3) [i.e., 32/48 (66.7%) and 28/76 (36.8%), respectively]. Downgraded FNAC results were significantly more frequent in EU-TIRADS 2/3 (p=0.001) while upgraded FNAC were present only in EU-TIRADS 4/5 (24/24, 100.0%). The inter-observer agreement among LV and HV thyroid services was poor. The EU-TIRADS 4 and 5 categories included all the malignant nodules with FNAC results reclassified as higher risk (i.e., TIR3B-TIR4-TIR5) by the high-volume cytology service.

Mediterranean Diet and Thyroid: An Interesting Alliance.

The Mediterranean diet, recognized as being cultural heritage by UNESCO, is mostly plant-based and includes a high consumption of whole-grain, fruit, and vegetables with a moderate consumption of alcohol during meals. Thus, it provides a small amount of saturated fatty acids and a high quantity of antioxidants and fiber. For this reason, it has been considered to have an important role in preventing cardiovascular diseases, chronic kidney diseases, type 2 diabetes mellitus, and cancer, but its relationship with thyroid function and diseases is still under debate. The aim of this review was to search for the possible correlation between the Mediterranean diet and thyroid function, and to critically evaluate the pathophysiological link between selected food intake and thyroid disorders.

European Safety Analysis of mRNA and Viral Vector COVID-19 Vaccines on Glucose Metabolism Events.

Few data have been published on the effects of impaired glucose metabolism induced by COVID-19 vaccines. We decided to perform a study to describe Individual Case Safety Reports (ICSRs) of impaired glucose metabolism events reported in the European database (Eudravigilance, EV). ICSRs were retrieved from the online website of Eudravigilance. The reporting odds ratios (ROR) were computed to assess the reporting frequency for COVID-19 mRNA vaccines compared to COVID-19 viral vector-based vaccines. A total of 3917 ICSRs with a COVID-19 vaccine suspected were retrieved, with a total of 4275 impaired glucose metabolism events. Overall, the most reported events were related to "high glucose levels" (2012; 47.06%). The mRNA vaccines were associated with an increased reporting frequency of "type 1 diabetes mellitus" (ROR 1.86; 95% CI 1.33-2.60), "type 2 diabetes mellitus" (ROR 1.58; 95% CI 1.03-2.42), "high glucose levels" (ROR 1.16; 95% CI 1.06-1.27), "diabetes mellitus inadequate control" (ROR 1.63; 95% CI 1.25-2.11), and "hypoglycemia" (ROR 1.62; 95% CI 1.41-1.86) compared to viral vector-based vaccines. mRNA COVID-19 vaccines were associated with an increased reporting frequency of alterations of glucose homeostasis compared to viral-vector COVID-19 vaccines. Clinicians should be aware of these events to better manage glycemic perturbations. Larger nationwide studies are warranted to verify these findings.