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Objective: This study aimed to compare robotic pancreatoduodenectomy with vein resection (PD-VR) based on the incidence of severe postoperative complications (SPC)., Background: Robotic pancreatoduodenectomy has been gaining momentum in recent years. Vein resection is frequently required in this operation, but no study has compared robotic and open PD-VR using a matched analysis., Methods: This was an intention-to-treat study designed to demonstrate the noninferiority of robotic to open PD-VR (2011-2021) based on SPC. To achieve a power of 80% (noninferiority margin:10%; α error: 0.05; ß error: 0.20), a 1:1 propensity score-matched analysis required 35 pairs., Results: Of the 151 patients with PD-VR (open = 115, robotic = 36), 35 procedures per group were compared. Elective conversion to open surgery was required in 1 patient with robotic PD-VR (2.9%). One patient in both groups experienced partial vein thrombosis. SPC occurred in 7 (20.0%) and 6 patients (17.1%) in the robotic and open PD-VR groups, respectively ( P = 0.759; OR: 1.21 [0.36-4.04]). Three patients died after robotic PD-VR (8.6%) and none died after open PD-VR ( P = 0.239). Robotic PD-VR was associated with longer operative time (611.1 ± 13.9 minutes vs 529.0 ± 13.0 minutes; P < 0.0001), more type 2 vein resection (28.6% vs 5.7%; P = 0.0234) and less type 3 vein resection (31.4% vs 71.4%; P = 0.0008), longer vein occlusion time (30 [25.3-78.3] minutes vs 15 [8-19.5] minutes; P = 0.0098), less blood loss (450 [200-750] mL vs 733 [500-1070.3] mL; P = 0.0075), and fewer blood transfusions (intraoperative: 14.3% vs 48.6%; P = 0.0041) (perioperative: 14.3% vs 60.0%; P = 0.0001)., Conclusions: In this study, robotic PD-VR was noninferior to open PD-VR for SPC. Robotic and open PD-VR need to be compared in randomized controlled trials., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aging is the result of several complex and multifactorial processes, where several agents contribute to an increased intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms that are finely regulated and strictly interconnected, initiating or contributing to biological changes and anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic effects. Vitamin D (VitD) is known to have a positive impact not only on muscle and bone health but also on several extra-skeletal districts, due to the widespread presence of Vitamin D Receptors (VDRs). VitD and VDR could be molecules potentially targeting the hallmarks of the aging network. To date, evidence about the potential effects of VitD on the hallmarks of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seem to confirm the modulatory effect of VitD on some hallmarks of aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

Aims: Given the increasing number of individuals developing metabolic dysfunction-associated steatotic liver disease (MASLD) and the low rate of those with progressive liver disease, there is a pressing need to conceive affordable biomarkers to assess MASLD in general population settings. Herein, we aimed to investigate the performance of the ultrasound-derived fat fraction (UDFF) for hepatic steatosis in high-risk individuals., Methods: A total of 302 Europeans with obesity, type 2 diabetes, or a clinical history of hepatic steatosis were included in the analyses. Clinical, laboratory, and imaging data were collected using standardized procedures during a single screening visit in Rome, Italy. Hepatic steatosis was defined by controlled attenuation parameter (CAP) or ultrasound-based Hamaguchi's score. UDFF performance for hepatic steatosis was estimated by the area under the receiver operating characteristic curve (AUC)., Results: Overall, median (IQR) UDFF was 12% (7-20). UDFF was positively correlated with CAP (ρ = 0.73, p < 0.0001) and Hamaguchi's score (ρ = 0.79, p < 0.0001). Independent predictors of UDFF were circulating triglycerides, alanine aminotransferase (ALT), and ultrasound-measured visceral adipose tissue (VAT). UDFF AUC was 0.89 (0.85-0.93) and 0.92 (0.88-0.95) for CAP- and ultrasound-diagnosed hepatic steatosis, respectively. UDFF AUC for hepatic steatosis was higher than those of fatty liver index (FLI), hepatic steatosis index (HSI), CAP-score (CAPS), and ALT (p < 0.0001). Lower age, ALT, and VAT were associated with discordance between UDFF and ultrasound., Conclusions: UDFF may be a simple and accurate imaging biomarker to assess hepatic steatosis and monitor changes in hepatic fat content over time or in response to therapeutic interventions beyond clinical trials., (© 2024 John Wiley & Sons Ltd.)

Background: Visceral adiposity has been associated with an increased risk of critical illness in COVID-19 patients. However, if it also associates to a poor survival is still not well established. The aim of the study was to assess the relationship between abdominal fat distribution and COVID-19 mortality., Methods: In this six-month longitudinal cohort study, abdominal visceral (VAT) and subcutaneous adipose tissues (SAT) were measured by computed tomography in a cohort of 174 patients admitted to the emergency department with a diagnosis of COVID-19, during the first wave of pandemic. The primary exposure and outcome measures were VAT and SAT at hospital admission, and death at 30 and 180 days, respectively., Results: Overall survival was not different according to VAT (p = 0.94), SAT (p = 0.32) and VAT/SAT ratio (p = 0.64). However, patients in the lowest SAT quartile (thickness ≤ 11.25 mm) had a significantly reduced survival compared to those with thicker SAT (77 vs. 94% at day 30; 74 vs. 91% at day 180, p = 0.01). Similarly, a thinner SAT was associated with lower survival in Intensive Care Unit (ICU) admitted patients, independently of sex or age (p = 0.02). The VAT/SAT ratio showed a non-linear increased risk of ICU admission, which plateaued out and tended for inversion at values greater than 1.9 (p = 0.001), although was not associated with increased mortality rate., Conclusions: In our cohort, visceral adiposity did not increase mortality in patients with COVID-19, but low SAT may be associated with poor survival., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Mortality in type 2 diabetes is twice that of the normoglycemic population. Unravelling biomarkers that identify high-risk patients for referral to the most aggressive and costly prevention strategies is needed., Objective: To validate in type 2 diabetes the association with all-cause mortality of a 14-metabolite score (14-MS) previously reported in the general population and whether this score can be used to improve well-established mortality prediction models., Methods: This is a sub-study consisting of 600 patients from the "Sapienza University Mortality and Morbidity Event Rate" (SUMMER) study in diabetes, a prospective multicentre investigation on all-cause mortality in patients with type 2 diabetes. Metabolic biomarkers were quantified from serum samples using high-throughput proton nuclear magnetic resonance metabolomics., Results: In type 2 diabetes, the 14-MS showed a significant (p < 0.0001) association with mortality, which was lower (p < 0.0001) than that reported in the general population. This difference was mainly due to two metabolites (histidine and ratio of polyunsaturated fatty acids to total fatty acids) with an effect size that was significantly (p = 0.01) lower in diabetes than in the general population. A parsimonious 12-MS (i.e. lacking the 2 metabolites mentioned above) improved patient discrimination and classification of two well-established mortality prediction models (p < 0.0001 for all measures)., Conclusions: The metabolomic signature of mortality in the general population is only partially effective in type 2 diabetes. Prediction markers developed and validated in the general population must be revalidated if they are to be used in patients with diabetes., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Introduction: The first-choice vascular access to starting dialysis in patients with End Stage Renal Disease (ESRD) is autogenous distal arteriovenous-fistula (AVF) to spare vascular district avoiding proximal fistula complications. One of most significant exclusion criteria to create distal AVF is still now the presence of huge calcification of the feeding artery due to large numbers of early failure (EF) and failure in maturation (FTM). In recent years the possibility to use new devices able to deliver intravascular lithotripsy (IVL) to treat high calcified stenosis could be a possibility to recruit these marginal arteries to create distal AVF., Methods: ESRD patients with totally calcified radial artery wall were enrolled to participate to this prospective, single arm, multicentric study. The selected patients were treated with intraoperative IVL at surgical time, during anastomosis creation to soften calcified radial artery. Patients were followed 1 month after surgery with eco-doppler, for flow and vessels maturation assessment. At 3 month was investigated how many patients have started dialysis treatment with two needle cannulation and good efficiency., Results: Nineteen distal forearm radio-cephalic fistula were built in 19 patients. One-month doppler assessment showed mean AVF flow of 743 ml/min and efferent vein caliper of 6.46 mm. At 3 months 14 patient have started stable 2 needles dialysis (other three patients were not yet dialysis dependent CKD). Were observed one immediate failure, one failure in maturation, and two late failures at 4 and 16 months respectively. Sixteen months primary and secondary patency was 78.9% and 89.5% respectively., Conclusion: These results showed how intraoperative IVL could help to recruit huge calcified marginal artery to create autogenous distal forearm AVF, avoiding proximal AVF, risking distal ischemia syndrome, and sparing vascular district to eventually rebuilt more proximal AVF in future., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Living donor kidney transplantation (LDKTx) is recommended by all scientific societies. Living donor nephrectomy (LDN) is probably one of the safest surgical procedures, but it carries some risk for healthy donors. The aim of this study is to provide a snapshot of LDKTx activities in Italy and ask about safety measures implemented in LDN. Data on LDKTx were extracted from the national database. Safety measures were examined through a specific survey. Between 2001 and 2022 40,663 kidney transplants (31.4 per million population-pmp) were performed, including 4731 LDKTx (3.7 pmp). There was no postoperative death of the donor. After a median follow-up of 52.2 months [IQR:17.9-99.5], the 10-year donor survival rate was 93.38% (CI:97.52-98.94). There was evidence of renal disease in 65 donors (1.8%), including 42 (1.1%) with stage III end-stage renal disease. Twenty-nine out of 35 transplant centers (TC) involved in LDKTx responded to the survey (82.9%). Six TCs (21.4%) had a total experience of 20 or fewer LDN. Minimally invasive LDN was the first choice at 24 TC (82.8%). At 10 TC (37.0%) only one surgeon performed LDN. Nineteen TCs (65.5%) had a surgical safety checklist for LDN and 14 had a postoperative surveillance protocol. The renal artery was occluded in 3 TCs (10.3%) mainly by non-transfixion methods (including clips). Redundancy of key safety systems in the operating room was available in 22 of 29 centers (75.8%). In summary, LDKTx should be further implemented in Italy. Donor safety should be improved through the implementation of a national procedural protocol., (© 2023. The Author(s).)

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery., (© 2023. The Author(s).)

Cutaneous myoepithelioma is a rare neoplasm of the skin that has become more widely recognized in recent years despite significant diagnostic pitfalls. It is a benign neoplasm with a high recurrence rate if not excised radically, and must be distinguished from its malignant counterpart. Few cases have been described so far and, to our knowledge, no cases in the finger of a child exist in the literature. We report the case of a 15 year-old boy affected by a rare form of locally aggressive spindle-cell myoepithelioma, and suggest a new multidisciplinary approach combining surgical excision and custom brachytherapy., (Copyright © 2023 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Background: The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT)., Methods: One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m 2 ) participated in lifestyle intervention trials at our medical center. All underwent baseline measurements of bone strength (failure load and stiffness) using μFEA from HR-pQCT of the distal radius and tibia. In addition, SO indices [appendicular lean mass/weight (ALM/W) and percent body fat (FM%)] by dual-energy X-ray absorptiometry and handgrip strength (HGS) by dynamometry were assessed. SO was diagnosed and staged based on the 2022 ESPEN and EASO expert consensus statement., Results: Both ALM/W and HGS were positively correlated explaining 28% to 36% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). In contrast, FM% was negatively correlated explaining 22% to 31% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). The associations of SO indices with failure load and stiffness remained significant after controlling for age, sex, race/ethnicity, diabetes, and 25-OH vitamin D (ALM/W: R 2 =  0.301 to 0.448, HGS: R 2 =  0.346 to 0.472, FM%: R 2 =  0.299 to 0.432) ( p < 0.001 to 0.011). SO was diagnosed in 75/189 (40%) participants with 66/75 (88%) having functional or metabolic complications (stage II). Participants with SO had lower failure load and stiffness at the distal radius than participants with no SO (both p < 0.05)., Conclusion: These findings demonstrate that lower muscle mass and strength and higher fat mass may impair bone quality. Therefore, interventions that focus on preserving muscle mass and strength while reducing fat mass may be important to decrease fracture risk when older adults with obesity undertake lifestyle intervention therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Gregori, Paudyal, Barnouin, Celli, Segoviano-Escobar, Armamento-Villareal, Napoli, Qualls and Villareal.)

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 HbA 1c or individualized HbA 1c 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., (© 2023. The Author(s).)

Pancreas sparing total duodenectomy (PSTD) is an exceedingly rare procedure that is performed mostly for benign disease, widely involving the duodenum, that cannot be treated otherwise. PSTD requires meticulous dissection as well as reconstruction of both biliary and pancreatic drainage. Despite these technical aspects appear to be ideal for robotic assistance, robotic PSTD has not been described yet.Robotic PSTD was successfully performed in two patients. In both patients biliary and pancreatic drainage were reconstructed on the second jejunal loop, which was pulled in the duodenal bed. In the first patient, gastro-jejunostomy was performed on the blind end of the neo-duodenum (Billorth I type gastric reconstruction). In the second patient, gastro-jejunostomy was achieved in an antecolic position, 40 cm downstream the neo-ampulla in the second patient (Billorth II type gastric reconstruction). In both patients, indication to PSTD was duodenal polyps not amenable to endoscopic removal. The first patient suffered from prolonged delayed gastric emptying, but she is currently doing well 5 years and beyond after the procedure. The second patient complained of mild delayed gastric emptying that resolved spontaneously. He is now doing well 5 months after surgery.We have shown the feasibility of robotic PSTD in what we believe to be a world premiere. Further experience is required to refine the procedure and improve outcomes., (© 2023. Italian Society of Surgery (SIC).)

Careful preoperative planning is key in minimally invasive radical antegrade modular pancreatosplenectomy (MI-RAMPS). This retrospective study aims to show the practical implications of computed tomography distance between the right margin of the tumor and either the left margin of the spleno-mesenteric confluence (d-SMC) or the gastroduodenal artery (d-GDA). Between January 2011 and June 2022, 48 minimally invasive RAMPS were performed for either pancreatic cancer or malignant intraductal mucinous papillary neoplasms. Two procedures were converted to open surgery (4.3%). Mean tumor size was 31.1 ± 14.7 mm. Mean d-SMC was 21.5 ± 18.5 mm. Mean d-GDA was 41.2 ± 23.2 mm. A vein resection was performed in 10 patients (20.8%) and the pancreatic neck could not be divided by an endoscopic stapler in 19 operations (43.1%). In patients requiring a vein resection, mean d-SMC was 10 mm (1.5-15.5) compared to 18 mm (10-37) in those without vein resection (p = 0.01). The cut-off of d-SMC to perform a vein resection was 17 mm (AUC 0.75). Mean d-GDA was 26 mm (19-39) mm when an endoscopic stapler could not be used to divide the pancreas, and 46 mm (30-65) when the neck of the pancreas was stapled (p = 0.01). The cut-off of d-GDA to safely pass an endoscopic stapler behind the neck of the pancreas was 43 mm (AUC 0.75). Computed tomography d-SMC and d-GDA are key measurements when planning for MI-RAMPS., (© 2023. The Author(s).)

The prognostic value of carbohydrate antigen 125 (Ca 125) is emerging also in pancreatic cancer (PDAC). In this study, we aim to define the prognostic value of Ca 125 in resected PDAC of the head of the pancreas. This is a single-center, retrospective study. Data from patients with a pre-operative assay of Ca 125 who underwent a pancreatic resection for PDAC between 2010 and 2018 were analyzed. As per National Comprehensive Cancer Guidelines, tumors were classified in resectable (R-PDAC), borderline resectable (BR-PDAC), and locally advanced (LA-PDAC). The Kaplan-Meier method was used to evaluate the overall survival. Cox proportional hazard regression was used to evaluate the role of pre-operative Ca 125 in predicting survival (while adjusting for confounders). The maximally selected log-rank statistic was used to identify a Ca 125 cut-off defining two groups with different survival probability. Inclusion criteria were met by 207 patients (R-PDAC: 80, BR-PDAC: 91, and LA-PDAC: 36). Ca 125 predicted overall survival before and after adjusting for confounding factors in all categories of anatomic resectability (R-PDAC: HR = 4.3; p = 0.0249) (BR-PDAC: HR = 7.82; p = 0.0024) (LA-PDAC: HR = 11.4; p = 0.0043). In BR-PDAC and LA-PDAC (n = 127), the division in two groups (high vs. low Ca 125) correlated with T stage (p = 0.0317), N stage (p = 0.0083), mean LN ratio (p = 0.0292), and tumor grading (p = 0.0143). This study confirmed the prognostic value of Ca125 in resected pancreatic cancer and, therefore, the importance of biologic over anatomic resectability. Ca 125 should be routinely assayed in surgical candidates with PDAC., (© 2023. The Author(s).)

This retrospective analysis of the prospective IGOMIPS registry reports on 1191 minimally invasive pancreatic resections (MIPR) performed in Italy between 2019 and 2022, including 668 distal pancreatectomies (DP) (55.7%), 435 pancreatoduodenectomies (PD) (36.3%), 44 total pancreatectomies (3.7%), 36 tumor enucleations (3.0%), and 8 central pancreatectomies (0.7%). Spleen-preserving DP was performed in 109 patients (16.3%). Overall incidence of severe complications (Clavien-Dindo ≥ 3) was 17.6% with a 90-day mortality of 1.9%. This registry analysis provided some important information. First, robotic assistance was preferred for all MIPR but DP with splenectomy. Second, robotic assistance reduced conversion to open surgery and blood loss in comparison to laparoscopy. Robotic PD was also associated with lower incidence of severe postoperative complications and a trend toward lower mortality. Fourth, the annual cut-off of ≥ 20 MIPR and ≥ 20 MIPD improved selected outcome measures. Fifth, most MIPR were performed by a single surgeon. Sixth, only two-thirds of the centers performed spleen-preserving DP. Seventh, DP with splenectomy was associated with higher conversion rate when compared to spleen-preserving DP. Eighth, the use of pancreatojejunostomy was the prevalent reconstruction in PD. Ninth, final histology was similar for MIPR performed at high- and low-volume centers, but neoadjuvant chemotherapy was used more frequently at high-volume centers. Finally, this registry analysis raises important concerns about the reliability of R1 assessment underscoring the importance of standardized pathology of pancreatic specimens. In conclusion, MIPR can be safely implemented on a national scale. Further analyses are required to understand nuances of implementation of MIPR in Italy., (© 2023. The Author(s).)

Novel antidiabetic drugs have the ability to produce anti-inflammatory effects regardless of their glucose-lowering action. For this reason, these molecules (including GLP-1 RAs and DPP-4is) were hypothesized to be effective against COVID-19, which is characterized by cytokines hyperactivity and multiorgan inflammation. The aim of our work is to explore the potential protective role of GLP-1 RAs and DPP-4is in COVID-19 (with the disease intended to be a model of an acute stressor) and non-COVID-19 patients over a two-year observation period. Retrospective and one-versus-one analyses were conducted to assess the impact of antidiabetic drugs on the need for hospitalization (in both COVID-19- and non-COVID-19-related cases), in-hospital mortality, and two-year mortality. Logistic regression analyses were conducted to identify the variables associated with these outcomes. Additionally, log-rank tests were used to plot survival curves for each group of subjects, based on their antidiabetic treatment. The performed analyses revealed that despite similar hospitalization rates, subjects undergoing home therapy with GLP-1 RAs exhibited significantly lower mortality rates, even over a two-year period. These individuals demonstrated improved survival estimates both within hospital and non-hospital settings, even during a longer observation period.

Background: Novel biomarkers of vascular disease in diabetes could help identify new mechanistic pathways. Osteocalcin, osteoprotegerin, and osteopontin are key molecules involved in bone and vascular calcification processes, both of which are compromised in diabetes. We aimed to evaluate possible associations of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease (CVD) and diabetic retinopathy (DR) among people with type 2 diabetes (T2D)., Materials and Methods: Osteocalcin, osteoprotegerin, and osteopontin concentrations were measured at enrolment in 848 participants with T2D from the Sapienza University Mortality and Morbidity Event Rate (SUMMER) Study (ClinicalTrials.gov: NCT02311244). Logistic regression models and propensity score matching were used to assess possible associations of osteocalcin, osteoprotegerin, and osteopontin with a history of CVD and with evidence of any grade of DR adjusting for confounders., Results: Previous CVD was reported in 139 (16.4%) participants, while 144 (17.0%) had DR. After adjusting for possible confounders, osteocalcin but not osteoprotegerin or osteopontin concentrations were associated with a history of CVD (Odds Ratio [OR] and 95% CI for one standard deviation (SD) increase in osteocalcin concentrations (natural log): 1.35 (1.06-1.72), p = 0.014). Associations with prevalent DR were seen for osteoprotegerin (OR for one SD increase in osteoprotegerin concentrations (natural log): 1.25 (1.01-1.55), p = 0.047) and osteopontin (OR for one SD increase in osteopontin concentrations (natural log): 1.25 (1.02-1.53), p = 0.022), but not osteocalcin., Conclusions: In T2D, higher serum osteocalcin concentrations are associated with macrovascular complications and higher osteoprotegerin and osteopontin concentrations with microvascular complications, suggesting that these osteokines might be involved in pathways directly related to vascular disease., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Purpose: The aim of this study was to evaluate the relationships between health literacy, unrealistic optimism, and adherence to glycometabolic disease management related to erectile dysfunction (ED) in male patients with type 2 diabetes (T2D) or preDM., Materials and Methods: This prospective observational study enroled 167 consecutive patients with T2D and ED. All patients underwent the following examinations: (a) medical history collection; (b) Body Mass Index (BMI) determination; (c) hormonal and biochemical assessment; (d) duration of T2D, complications and treatment; (e) International Index of Erectile Function-5 questionnaire to assess ED; and (f) validated questionnaire to evaluate health literacy, unrealistic optimism, and treatment adherence., Results: Overall, mean age was 62.5 ± 9.4 years (range: 20-75) and mean BMI was 28.4 ± 4.8 kg/m 2 (range: 18.4-46.6). The mean IIEF-5 score was 15.4 ± 5.2 (range: 5-25). The majority of patients showed high health literacy. However, low health literacy was found in patients with higher IIEF-5 scores and high BMI. Unrealistic optimism was low in most patients. Higher adherence to treatment was found in patients who reported regular physical activity, who followed a diet, and in patients with a family history of T2D. Regarding anti-diabetic treatment, patients treated with insulin showed higher health literacy than patients not treated with other medications, whereas higher adherence was found in patients using SGLT2-i., Conclusions: This study highlighted the close relationship between metabolic compensation, BMI, ED, and psychological attitudes, including health literacy and unrealistic optimism., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Purpose: Bone is one of the main targets of hormones and endocrine diseases are frequent causes of secondary osteoporosis and fractures in real-world clinical practice. However, diagnosis of skeletal fragility and prediction of fractures in this setting could be a challenge, since the skeletal alterations induced by endocrine disorders are not generally captured by dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD), that is the gold standard for diagnosis of osteoporosis in the general population. The aim of this paper is to review the existing evidence related to bone quality features in endocrine diseases, proposing assessment with new techniques in the future., Methods: A comprehensive search within electronic databases was performed to collect reports of bone quality in primary hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypercortisolism, growth hormone deficiency, acromegaly, male hypogonadism and diabetes mellitus., Results: Using invasive and non-invasive techniques, such as high-resolution peripheral quantitative computed tomography or DXA measurement of trabecular bone score (TBS), several studies consistently reported altered bone quality as predominant determinant of fragility fractures in subjects affected by chronic endocrine disorders., Conclusions: Assessment of skeletal fragility in endocrine diseases might take advantage from the use of techniques to detect perturbation in bone architecture with the aim of best identifying patients at high risk of fractures., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Type-2 diabetes mellitus (DM) represents one of the most important risk factors for cardiovascular diseases (CVD). Hyperglycemia and glycemic variability are not the only determinant of the increased cardiovascular (CV) risk in diabetic patients, as a frequent metabolic disorder associated with DM is dyslipidemia, characterized by hypertriglyceridemia, decreased high-density lipoprotein (HDL) cholesterol levels and a shift towards small dense low-density lipoprotein (LDL) cholesterol. This pathological alteration, also called diabetic dyslipidemia, represents a relevant factor which could promotes atherosclerosis and subsequently an increased CV morbidity and mortality. Recently, the introduction of novel antidiabetic agents, such as sodium glucose transporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs), has been associated with a significant improvement in CV outcomes. Beyond their known action on glycemia, their positive effects on the CV system also seems to be related to an ameliorated lipidic profile. In this context, this narrative review summarizes the current knowledge regarding these novel anti-diabetic drugs and their effects on diabetic dyslipidemia, which could explain the provided global benefit to the cardiovascular system.

Introduction: Psychosocial factors frequently occur in kidney transplant recipients (KTRs), leading to behavioral alterations and reduced therapeutic adherence. However, the burden of psychosocial disorders on costs for KTRs is unknown. The aim of the study is to identify predictors of healthcare costs due to hospital admissions and emergency department access in KTRs., Methods: This is a longitudinal observational study conducted on KTRs aged >18 years, excluding patients with an insufficient level of autonomy and cognitive disorder. KTRs underwent psychosocial assessment via two interviews, namely the Mini-International Neuropsychiatric Interview 6.0 (MINI 6.0) and the Diagnostic Criteria for Psychosomatic Research Interview (DCPR) and via the Edmonton Symptom Assessment System Revised (ESAS-R) scale, a self-administrated questionnaire. Sociodemographic data and healthcare costs for hospital admissions and emergency department access were collected in the 2016-2021 period. Psychosocial determinants were as follows: (1) ESAS-R psychological and physical score; (2) symptomatic clusters determined by DCPR (illness behavior cluster, somatization cluster, and personological cluster); and (3) ICD diagnosis of adjustment disorder, anxiety disorder, and mood disorder. A multivariate regression model was used to test the association between psychosocial determinants and total healthcare costs., Results: A total of 134 KTRs were enrolled, of whom 90 (67%) were men with a mean age of 56 years. A preliminary analysis of healthcare costs highlighted that higher healthcare costs are correlated with worse outcomes and death ( p < 0.001). Somatization clusters ( p = 0.020) and mood disorder ( p < 0.001) were positively associated with costs due to total healthcare costs., Conclusions: This study showed somatization and mood disorders could predict costs for hospital admissions and emergency department access and be possible risk factors for poor outcomes, including death, in KTRs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zerbinati, Guerzoni, Napoli, Preti, Esposito, Caruso, Bulighin, Storari, Grassi and Battaglia.)

Background: Difficulty scoring systems are important for the safe, stepwise implementation of new procedures. We designed a retrospective observational study for building a difficulty score for robotic pancreatoduodenectomy., Methods: The difficulty score (PD-ROBOSCORE) aims at predicting severe postoperative complications after robotic pancreatoduodenectomy. The PD-ROBOSCORE was developed in a training cohort of 198 robotic pancreatoduodenectomies and was validated in an international multicenter cohort of 686 robotic pancreatoduodenectomies. Finally, all centers tested the model during the early learning curve (n = 300). Growing difficulty levels (low, intermediate, high) were defined using cut-off values set at the 33rd and 66th percentile (NCT04662346)., Results: Factors included in the final multivariate model were a body mass index of ≥25 kg/m 2 for males and ≥30 kg/m 2 for females (odds ratio:2.39; P < .0001), borderline resectable tumor (odd ratio:1.98; P < .0001), uncinate process tumor (odds ratio:1.69; P < .0001), pancreatic duct size <4 mm (odds ratio:1.59; P < .0001), American Society of Anesthesiologists class ≥3 (odds ratio:1.59; P < .0001), and hepatic artery originating from the superior mesenteric artery (odds ratio:1.43; P < .0001). In the training cohort, the absolute score value (odds ratio = 1.13; P = .0089) and difficulty groups (odds ratio = 2.35; P = .041) predicted severe postoperative complications. In the multicenter validation cohort, the absolute score value predicted severe postoperative complications (odds ratio = 1.16, P < .001), whereas the difficulty groups did not (odds ratio = 1.94, P = .082). In the learning curve cohort, both absolute score value (odds ratio:1.078, P = .04) and difficulty groups (odds ratio: 2.25, P = .017) predicted severe postoperative complications. Across all cohorts, a PD-ROBOSCORE of ≥12.51 doubled the risk of severe postoperative complications. The PD-ROBOSCORE score also predicted operative time, estimated blood loss, and vein resection. The PD-ROBOSCORE predicted postoperative pancreatic fistula, delayed gastric emptying, postpancreatectomy hemorrhage, and postoperative mortality in the learning curve cohort., Conclusion: The PD-ROBOSCORE predicts severe postoperative complications after robotic pancreatoduodenectomy. The score is readily available via www.pancreascalculator.com., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: The risk of fragility fractures is increased in both type 1 and type 2 diabetes. Numerous biochemical markers reflecting bone and/or glucose metabolism have been evaluated in this context., Objective: This review summarizes current data on biochemical markers in relation to bone fragility and fracture risk in diabetes., Methods: A group of experts from the International Osteoporosis Foundation and European Calcified Tissue Society reviewed the literature focusing on biochemical markers, diabetes, diabetes treatments, and bone in adults., Results: Although bone resorption and bone formation markers are low and poorly predictive of fracture risk in diabetes, osteoporosis drugs seem to change bone turnover markers (BTMs) in diabetics similarly to nondiabetics, with similar reductions in fracture risk. Several other biochemical markers related to bone and glucose metabolism have been correlated with bone mineral density and/or fracture risk in diabetes, including osteocyte-related markers such as sclerostin, glycated hemoglobin A1c (HbA1c) and advanced glycation end products, inflammatory markers, and adipokines, as well as insulin-like growth factor-1 and calciotropic hormones., Conclusion: Several biochemical markers and hormonal levels related to bone and/or glucose metabolism have been associated with skeletal parameters in diabetes. Currently, only HbA1c levels seem to provide a reliable estimate of fracture risk, while BTMs could be used to monitor the effects of antiosteoporosis therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The trabecular and cortical bone assessed by bone strain index seems not to be significantly affected in NHPT., Introduction: The natural history and bone involvement of normocalcemic hyperparathyroidism (NHPT) are not fully clarified yet. The bone strain index (BSI) is a deformation index based on the finite element method and can be applied to DXA scans. In this study, we aim to assess BSI in subjects with NHPT., Method: A case-control study included 170 subjects: 40 subjects with NHPT, 50 subjects with primary hypercalcemic hyperparathyroidism (PHPT), and 80 controls (age- and sex-matched with the NPTH group)., Results: Lumbar spine (LS) bone mineral density (BMD), femoral neck (FN) BMD, total hip (TH) BMD, and TBS were similar between NHPT and both PHPT and controls. FN-BSI was lower in NHPT compared to PHPT (1.52 ± 0.31 vs 1.72 ± 0.42 p = 0.031) while there were no differences between NHPT and controls. TH-BSI was lower in NHPT compared to PHPT (1.36 ± 0.23 vs 1.52 ± 0.34, p = 0.030), while there were no differences between NHPT and controls. LS-BSI was not different between NHPT and both PHPT and controls., Conclusion: The trabecular and cortical bones assessed by BSI seem not to be significantly impaired in NHPT. Further prospective studies are needed to confirm these findings and to give an insight into the natural history of NHPT to improve knowledge and management of this condition., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Oxidative stress, a key mediator of cardiovascular disease, metabolic alterations, and cancer, is independently associated with menopause and obesity. Yet, among postmenopausal women, the correlation between obesity and oxidative stress is poorly examined. Thus, in this study, we compared oxidative stress states in postmenopausal women with or without obesity. Body composition was assessed via DXA, while lipid peroxidation and total hydroperoxides were measured in patient's serum samples via thiobarbituric-acid-reactive substances (TBARS) and derivate-reactive oxygen metabolites (d-ROMs) assays, respectively. Accordingly, 31 postmenopausal women were enrolled: 12 with obesity and 19 of normal weight (mean (SD) age 71.0 (5.7) years). Doubled levels of serum markers of oxidative stress were observed in women with obesity in women with obesity compared to those of normal weight (H 2 O 2 : 32.35 (7.3) vs. 18.80 (3.4) mg H 2 O 2 /dL; malondialdehyde (MDA): 429.6 (138.1) vs. 155.9 (82.4) mM in women with or without obesity, respectively; p < 0.0001 for both). Correlation analysis showed that both markers of oxidative stress increased with an increasing body mass index (BMI), visceral fat mass, and trunk fat percentage, but not with fasting glucose levels. In conclusion, obesity and visceral fat are associated with a greater increase in oxidative stress in postmenopausal women, possibly increasing cardiometabolic and cancer risks.

We evaluated the sex-specific difference in response upon participation in an exercise program with respect to the risk of adverse clinical outcomes among patients with peripheral artery disease (PAD) and claudication. The records of 400 PAD patients were assessed between 2012 and 2015. Two hundred of them were addressed to a walking program prescribed at the hospital and executed at home at symptom-free walking speed (Ex), while the remaining 200 acted as a control group (Co). The number and date of deaths, all-cause hospitalizations, and amputations for a 7-year period were collected from the regional registry. At baseline, no differences were observed (M EX n = 138; F EX n = 62; M CO n = 149; F CO n = 51). The 7-year survival rate was significantly higher in F EX (90%) than in M EX (82% hazard ratio, HR: 0.542 95% CI 0.331-0.885), F CO (45%, HR: 0.164 95% CI 0.088-0.305), and M CO (44%; HR: 0.157 95% CI 0.096-0.256). A significantly lower rate of hospitalization ( p < 0.001) and amputations ( p = 0.016) was observed for the Ex group compared to the Co group, without differences by sex. In conclusion, in PAD patients, active participation in a home-based pain-free exercise program was associated with a lower rate of death and better long-term clinical outcomes, particularly among women.

Background: Open pancreatoduodenectomy with vein resection (OPD-VR) is now standard of care in patients who responded to neoadjuvant therapies. Feasibility of robotic pancreatoduodenectomy (RPD) with vein resection (RPD-VR) was shown, but no study provided a detailed description of the technical challenges associated with this formidable operation. Herein, we describe the trips and tricks for technically successful RPD-VR., Methods: The vascular techniques used in RPD-VR were borrowed from OPD-VR, as well as from our experience with robotic transplantation of both kidney and pancreas. Vein resection was classified into 4 types according to the international study group of pancreatic surgery. Each type of vein resection was described in detail and shown in a video., Results: Between October 2008 and November 2021, a total of 783 pancreatoduodenectomies were performed, including 233 OPDs-VR (29.7%). RPD was performed in 256 patients (32.6%), and RPDs-VR in 36 patients (4.5% of all pancreatoduodenectomies; 15.4% of all pancreatoduodenectomies with vein resection; 14.0% of all RPDs). In RPD-VR vein resections were: 4 type 1 (11.1%), 10 type 2 (27.8%), 12 type 3 (33.3%) and 10 type 4 (27.8%). Vascular patches used in type 2 resections were made of peritoneum (n = 8), greater saphenous vein (n = 1), and deceased donor aorta (n = 1). Interposition grafts used in type 4 resections were internal left jugular vein (n = 8), venous graft from deceased donor (n = 1) and spiral saphenous vein graft (n = 1). There was one conversion to open surgery (2.8%). Ninety-day mortality was 8.3%. There was one (2.8%) partial vein thrombosis, treated with heparin infusion., Conclusions: We have reported 36 technically successful RPDs-VR. We hope that the tips and tricks provided herein can contribute to safer implementation of RPD-VR. Based on our experience, and according to data from the literature, we strongly advise that RPD-VR is performed by expert surgeons at high volume centers., (© 2023. The Author(s).)

This paper is one of the outcomes of the 5th International Conference "Controversies in Vitamin D" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Little is known about the changes in organs and tissues that may make elder patients more vulnerable to acute stressors such as SARS-CoV-2 infection., Methods: In 80 consecutive elderly patients with SARS-CoV-2 infection, we evaluated the association between the descending thoracic aorta calcium score, L1 bone density and T12 skeletal muscle density measured on the same scan by high-resolution computed tomography., Results: At median regression, the ln-transformed DTA calcium score was inversely associated with L1 bone density (-0.02, 95%CI -0.04 to -0.01 ln-Agatston units for an increase of 1 HU) and with T12 muscle density (-0.03, -0.06 to -0.001 ln-Agatston units for an increase of 1 HU). At penalized logistic regression, an increase of 1 ln-Agatston unit of DTA calcium score was associated with an OR of death of 1.480 (1.022 to 2.145), one of 1 HU of bone density with an OR of 0.981 (0.966 to 0.996) and one of 1 HU of muscle density with an OR of 0.973 (0.948 to 0.999). These relationships disappeared after correction for age and age was the stronger predictor of body composition and death., Conclusions: Age has a big effect on the relationship between vascular calcifications, L1 bone density and T12 muscle density and on their relationship with the odds of dying.

Objective: To assess postoperative 90-day outcomes after minimally invasive (laparoscopic/robot-assisted) total pancreatectomy (MITP) in selected patients versus open total pancreatectomy (OTP) among European centers., Background: Minimally invasive pancreatic surgery is becoming increasingly popular but data on MITP are scarce and multicenter studies comparing outcomes versus OTP are lacking. It therefore remains unclear if MITP is a valid alternative., Methods: Multicenter retrospective propensity-score matched study including consecutive adult patients undergoing MITP or OTP for all indications at 16 European centers in 7 countries (2008-2017). Patients after MITP were matched (1:1, caliper 0.02) to OTP controls. Missing data were imputed. The primary outcome was 90-day major morbidity (Clavien-Dindo ≥3a). Secondary outcomes included 90-day mortality, length of hospital stay, and survival., Results: Of 361 patients (99MITP/262 OTP), 70 MITP procedures (50 laparoscopic, 15 robotic, 5 hybrid) could be matched to 70 OTP controls. After matching, MITP was associated with a lower rate of major morbidity (17% MITP vs. 31% OTP, P = 0.022). The 90-day mortality (1.4% MITP vs. 7.1% OTP, P = 0.209) and median hospital stay (17 [IQR 11-24] MITP vs. 12 [10-23] days OTP, P = 0.876) did not differ significantly. Among 81 patients with PDAC, overall survival was 3.7 (IQR 1.7-N/A) versus 0.9 (IQR 0.5-N/ A) years, for MITP versus OTP, which was nonsignificant after stratification by T-stage., Conclusion: This international propensity score matched study showed that MITP may be a valuable alternative to OTP in selected patients, given the associated lower rate of major morbidity., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Celiac disease is a rising disorder and is becoming frequently diagnosed in recent years. To date, the only available treatment is the gluten-free diet (GFD). The role of gluten on components of metabolic syndrome and on related inflammatory response is still unclear due to controversial results. In recent years, scientific focus on this topic has been growing up, in particular regarding the role of the GFD on glycometabolic parameters and diabetes. In addition, studies on the remaining components showed discordant results, which was likely due to heterogeneous and large celiac disease populations and to the lack of prospective studies. Furthermore, knowledge about the role of the GFD on inflammatory cytokines and the relationship among vitamin D and celiac disease, metabolic syndrome (MS) and GFD is needed. In this narrative review, we provided evidence regarding the role of the GFD on glycometabolic parameters, cholesterol, triglycerides, waist circumference, blood pressure and inflammatory cascade, also evaluating the role of vitamin D, trying to summarize whether this nutritional pattern may be a value-added for subjects with dysmetabolic conditions. Finally, due to the limited findings and very low-certainty evidence, predominantly based on observational studies, the real effects of a GFD on different components of MS, however, are unclear; nevertheless, an improvement in HDL levels has been reported, although data on glycemic levels are discordant.

Purpose: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort., Methods: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included., Results: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%., Conclusion: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Triangle pancreatoduodenectomy adds to the conventional procedure the en bloc removal of the retroperitoneal lympho-neural tissue included in the triangular area bounded by the common hepatic artery (CHA), the superior mesenteric artery (SMA), and the superior mesenteric vein/portal vein. We herein aim to show the feasibility of "cold" triangle robotic pancreaticoduodenectomy (C-Tr-RPD) for pancreatic cancer (PDAC)., Methods: Cold dissection corresponds to sharp arterial divestment performed using only the tips of robotic scissors. After division of the gastroduodenal artery, triangle dissection begins by lateral-to-medial divestment of the CHA and anterior-to-posterior clearance of the right side of the celiac trunk. Next, after a wide Kocher maneuver, the origin of the SMA, and the celiac trunk are identified. After mobilization of the first jejunal loop and attached mesentery, the SMA is identified at the level of the first jejunal vein and is divested along the right margin working in a distal-to-proximal direction. Vein resection and reconstruction can be performed as required. C-Tr-RPD was considered feasible if triangle dissection was successfully completed without conversion to open surgery or need to use energy devices. Postoperative complications and pathology results are presented in detail., Results: One hundred twenty-seven consecutive C-Tr-RPDs were successfully performed. There were three conversions to open surgery (2.3%), because of pneumoperitoneum intolerance (n = 2) and difficult digestive reconstruction. Thirty-four patients (26.7%) required associated vascular procedures. No pseudoaneurysm of the gastroduodenal artery was observed. Twenty-eight patients (22.0%) developed severe postoperative complications (≥ grade III). Overall 90-day mortality was 7.1%, declining to 2.3% after completion of the learning curve. The median number of examined lymph nodes was 42 (33-51). The rate of R1 resection (7 margins < 1 mm) was 44.1%., Conclusion: C-Tr-RPD is feasible, carries a risk of surgical complications commensurate to the magnitude of the procedure, and improves staging of PDAC., (© 2022. The Author(s).)

Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and N -terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their association with clinical outcome. A series of 44 patients affected by advanced non-small cell lung cancer or renal cell carcinoma, without bone metastases, and treated with ICIs as monotherapy were enrolled. CTX-I and PINP plasma levels were assessed at baseline and after 3 months of ICIs treatment by ELISA kits. A significant increase of CTX-I with a concomitant decreasing trend towards the reduction of PINP was observed after 3 months of treatment. Intriguingly, CTX-I increase was associated with poor prognosis in terms of treatment response and survival. These data suggest a direct relationship between ICIs treatment, increased osteoclast activity and potential fracture risk. Overall, this study reveals that ICIs may act as triggers for skeletal events, and if confirmed in larger prospective studies, it would identify a new class of skeletal-related irAEs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier GmbH.)

Obesity is a multifactorial disease strongly associated with insulin resistance and/or type 2 diabetes mellitus. Correct nutrition represents a valid strategy to fight these dysmetabolic pathologies responsible for numerous diseases, including inflammatory and cardiovascular ones. Medical nutrition therapy, including a Mediterranean diet (MD) and a very low-calorie ketogenic diet (VLKCD), is the first-line treatment for prediabetes/diabetes and overweight/obesity. Eighty patients (forty women and forty men) affected by overweight/obesity and type 2 diabetes mellitus or impaired glucose tolerance or impaired fasting glucose (51 (ys) ± 1.75; BMI (kg/m 2 ) 33.08 ± 1.93; HA1c (%): 6.8% ± 0.25) were enrolled at the University Service of Diet Therapy, Diabetology and Metabolic Diseases, Policlinico Riuniti Hospital of Foggia, and subjected to a very-low-calorie Mediterranean diet and a very-low-calorie ketogenic Mediterranean diet for thirty days. Both diets result in a marked decrease in body weight (kg) and BMI (kg/m 2 ). At the same time, only the very-low-calories ketogenic Mediterranean diet reduced waist and hip circumferences. Both diets helped reduce fat mass, but a major loss was achieved in a very low-calorie ketogenic Mediterranean diet. Among gluco-metabolic parameters, only the very-low-calorie ketogenic Mediterranean diet group showed a significant decrease in fasting blood glucose and HbA1c, insulin, C-peptide total cholesterol, LDL, and triglycerides. The results of our study seem to show that the very-low-calorie ketogenic Mediterranean diet is a good strategy to improve rapidly metabolic, anthropometric, and body composition parameters in patients with prediabetes or diabetes and overweight/obesity.

Background: This study aims to describe the technique and the results of double-layer continuous suture hepaticojejunostomy (HJ) following pancreatoduodenectomy (PD) and total pancreatectomy (TP)., Methods: A prospectively maintained database was analyzed retrospectively to identify incidence and severity of biliary leaks (BL) (ISGLS definition), as well as of HJ stenosis (HJS), cholangitis, and need for redo-HJ (in patients with a follow-up ≥3 years) in a consecutive series of 800 procedures (PD = 603; TP = 197). Predictors of biliary complications were also identified., Results: BLs occurred in 5 patients (0.6%), including 2 (0.3%) combined pancreatic and biliary leaks. Rates of HJS, cholangitis, and need for redo-HJ were 6.1%, 5.4%, and 2.0%, respectively. Incidence of BL was 0.6% in open procedures (4/587) and 0.4% in robotic operations (1/213). Incidence of late biliary complications was also equivalent in open and robotic procedures. Occurrence of BL was predicted by ASA IV status and duodenal cancer, HJS by any associated vascular procedure and hepatic duct size < 8 mm, cholangitis by any associated vascular procedure and normal bilirubin/hepatic enzymes, and redo HJ by history of cholecystectomy and neuroendocrine tumor/cancer., Discussion: Double layer continuous suture HJ is associated with low BL rates, and an acceptable incidence of late complications., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Several studies have showed good/excellent results of thermal-ablation (TA) to reduce volume of benign thyroid nodule (TN). Nevertheless, no systematic review has reported information about clinical achievements with TA. Being the latter of high interest, this systematic review was undertaken to achieve high evidence about the efficacy of TA in reducing TN-related symptoms and cosmetic concerns. Radiofrequency (RFA) and laser (LA) therapies were considered. A comprehensive literature search of online databases was performed on January 2022 looking for studies reporting clinical results obtained by RFA or LA in terms of VAS (namely, Visual Analogic Scale) and cosmetic concerns. Initially, 318 records were found and 14 were finally included in the meta-analysis. VAS data were available in all RFA studies and the pooled mean reduction was of 3.09 points with significant heterogeneity. Cosmetic score data were available in 11 RFA studies and the pooled mean reduction was of 1.45 with significant heterogeneity. Regarding LA studies, 4 series reported VAS data and the pooled mean reduction was of 2.61 points with significant heterogeneity. The analysis of LA data about cosmetic concerns was not performed due to data paucity. Importantly, heterogeneities were not explained by meta-regression analyses using several covariates (i.e., baseline TN volume, follow-up duration, volume reduction rate). This systematic review showed that clinical data about TN TA efficacy are sparse and affected by high unexplained inconsistency. International societies should give indication about how we should clinically select and evaluate patients undergoing TN TA., (© 2022. The Author(s).)

Background: This is a proof of concept, as a pilot study, with the aim to evaluate continuous glucose monitoring metrics (CGM) in subjects with type 2 diabetes (T2DM), treated with nutritional therapy and metformin, before and after testosterone replacement therapy (TRT)., Methods: In this longitudinal observational study, subjects affected by T2DM and starting TRT for documented ED and hypogonadism were enrolled. All subjects mounted a CGM system during the v0 visit, one week before the beginning of the TRT (week-1), during v2, four weeks after the start of TRT (week 4), and v4 (week 12). CGM was worn for about 144 h after each visit., Results: A total of seven patients, referring to our clinic for erectile dysfunction (ED), were studied (aged 63.3 ± 2.3 years). Mean (± standard deviation) total testosterone level was 2.3 ± 0.6 ng/mL at baseline. After TRT, total testosterone level was 4.6 ± 3.04 ng/mL at week 4 and 3.93 ± 4.67 ng/mL at week 12. No significant differences were observed in TIR, TAR, TBR, estimated HbA1c, AUC below, and AUC above limit during the intervention period., Conclusions: This is the first study evaluating the effects of TRT on daily glucose excursions in subjects with T2DM and hypogonadism. Though we did not find any significant difference in key CGM metrics during the 12 weeks of TRT, this study confirms the glycometabolic safety of the TRT even on the most novel standardized glycemic targets.

Hypoparathyroidism is the only endocrine deficiency for which hormone replacement therapy is not the standard of care. Although conventional treatments may control hypocalcaemia, other complications such as hyperphosphatemia, kidney stones, peripheral calcifications, and bone disease remain unmet needs. This meta-analysis (PROSPERO registration number CRD42019126881) aims to evaluate and compare the efficacy and safety of PTH 1-34 and PTH 1-84 in restoring calcium metabolism in chronic hypoparathyroidism. EMBASE, PubMed, and CENTRAL databases were searched for randomized clinical trials or prospective studies published between January 1996 and March 2021. English-language trials reporting data on replacement with PTH 1-34 or PTH 1-84 in chronic hypoparathyroidism were selected. Three authors extracted outcomes, one author performed quality control, all assessed the risk of biases. Overall, data from 25 studies on 588 patients were analyzed. PTH therapy had a neutral effect on calcium levels, while lowering serum phosphate (-0.21 mmol/L; 95% confidence interval [CI], -0.31 to -0.11 mmol/L; p < 0.001) and urinary calcium excretion (-1.21 mmol/24 h; 95% CI, -2.03 to -0.41 mmol/24 h; p = 0.003). Calcium phosphate product decreased under PTH 1-84 therapy only. Both treatments enabled a significant reduction in calcium and calcitriol supplementation. PTH therapy increased bone turnover markers and lumbar spine mineral density. Quality of life improved and there was no difference in the safety profile between PTH and conventionally treated patients. Results for most outcomes were similar for the two treatments. Limitations of the study included considerable population overlap between the reports, incomplete data, and heterogeneity in the protocol design. In conclusion, the meta-analysis of data from the largest collection to date of hypoparathyroid patients shows that PTH therapy is safe, well-tolerated, and effective in normalizing serum phosphate and urinary calcium excretion, as well as enabling a reduction in calcium and vitamin D use and improving quality of life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Osteoporosis represents a relevant cause of morbidity in adult Thalassemia Major (TM) population. Antiresorptive drugs such as bisphosphonates were demonstrated effective in preventing bone loss. Teriparatide (TP) is an anabolic agent approved for osteoporosis management in the general population, but its use has been very limited in TM patients so far. We evaluated TP efficacy and safety in TM-associated osteoporosis in real-life clinical practice. Retrospective evaluation of 11 TM patients (6 males, 5 females; mean age = 45 ± 4.38 years) with severe osteoporosis and multiple fractures under TP treatment. Mean TP treatment duration was 19 ± 7 months. TP withdrawal was due to poor compliance and side effects (fever and osteo-muscular pain) in two and three patients, respectively. After 12 and 24 months, BMD significantly increased at lumbar (+ 19% and 22%) and femoral sites (+ 13% and 13%). Osteocalcin and cross-laps levels increased after 12 and 24 months (+ 225 and + 54.2%; + 159 and 141%, respectively). No new fractures were detected during TP treatment. Baseline VAS score values (3 ± 3) did not significantly change after 12 and 24 months (3 ± 3 and 2 ± 3, respectively). Five out of eleven patients developed side effects. TP might be an effective treatment for TM-associated osteoporosis since it improves BMD, especially at the lumbar spine, and prevents fragility fractures. TM patients may have a higher frequency of side effects, especially muscle and bone pain under TP treatment, as compared to no TM population. Further studies are needed., (© 2022. The Author(s).)

In hypoparathyroidism (HypoPT), calcium supplementation is virtually always required, although the disease is likely to be associated with an increased risk of nephrolithiasis. The use of calcium citrate (Ca-Cit) theoretically could have a positive impact on the nephrolithiasis risk because citrate salts are used to reduce this risk. Our objective was to evaluate the potential therapeutic advantage of Ca-Cit in comparison with calcium carbonate (CaCO 3 ) in HypoPT, on nephrolithiasis risk factors, as well as to their ability to maintain desirable serum calcium levels. We also evaluated these preparations on quality of life (QOL). This randomized, double-blind, crossover trial recruited 24 adults with postsurgical chronic hypoparathyroidism at Campus Bio-Medico University of Rome. Participants were randomized 1:1 to Ca-Cit or CaCO 3 for 1 month and then crossed over to the other treatment for another month. The primary outcomes were changes in albumin-adjusted serum calcium and in ion activity product of calcium oxalate levels (AP[CaOx] index). Secondary efficacy outcomes included changes in SF-36 survey score, fatigue score, constipation, and adverse events. No difference in terms of AP(CaOx) index was observed between the two groups. However, Ca-Cit was associated with a significant reduction in the oxalate/creatinine ratio compared with CaCO 3 (-2.46 mmol/mol [SD 11.93] versus 7.42 mmol/mol [SD 17.63], p = 0.029). Serum calcium and phosphorus concentration was not different between the two calcium preparations. Ca-Cit was associated with less constipation (p = 0.047). No difference was found in QOL scores. Although Ca-Cit did not modify the AP(CaOx) index when compared with CaCO 3, it was associated with a reduction in urinary oxalate excretion that could have a potential beneficial effect on nephrolithiasis risk. These results are likely to have clinical implications in HypoPT, particularly those who do not tolerate CaCO 3 and those affected by nephrolithiasis. A longer-term experience is needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Competing Interests: We declare no competing interests.

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and revascularization through percutaneous coronary interventions (PCI) significantly improves survival. In this setting, poor glycaemic control, regardless of diabetes, has been associated with increased incidence of peri-procedural and long-term complications and worse prognosis. Novel antidiabetic agents have represented a paradigm shift in managing patients with diabetes and cardiovascular diseases. However, limited data are reported so far in patients undergoing coronary stenting. This review intends to provide an overview of the biological mechanisms underlying hyperglycaemia-induced vascular damage and the contrasting actions of new antidiabetic drugs. We summarize existing evidence on the effects of these drugs in the setting of PCI, addressing pre-clinical and clinical studies and drug-drug interactions with antiplatelet agents, thus highlighting new opportunities for optimal long-term management of these patients.

Background: The purpose of this study was to evaluate the effect of diet and antihyperglycemic drugs on erectile dysfunction (ED) in a setting of subjects affected by diabetes mellitus (DM) or preDM., Methods: This is a prospective observational study on 163 consecutive subjects with preDM or DM. All patients have undergone a medical evaluation (age, Body Mass Index (BMI), family history of DM, duration of DM, smoking, physical activity, dyslipidemia, cardiovascular comorbidities, and testosterone and HbA1c levels) and the International Index of Erectile Function (IIEF)-5 questionnaire., Results: Overall, the mean age was 62.8 ± 9.3 years, and the mean BMI was 28.4 ± 4.6 kg/m 2 . The IIEF-5 score mean value was 14.4 ± 6.2 (range 4-25). Among all confounders investigated for their association with the IIEF-5 score, only age and the duration of DM among diabetic patients showed a significant trend. The IIEF-5 score was higher in patients using GLP-1a compared to insulin (16.7 ± 4.7 vs. 12.9 ± 6.2; p = 0.02). This association was confirmed after adjustment for age and duration of DM ( p = 0.01). All other treatments were similar (14.9 ± 6.2, 14.8 ± 9.2, 15.3 ± 5.4, and 13.6 ± 6.8 for metformin, sulfonylureas (SU), dipeptidyl-peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) treatment, respectively)., Conclusions: This prospective observational study increases attention and focus on the effect of antihyperglycemic drugs and diet on ED, above all about the role of new classes, showing a significant higher IIEF-5 mean value in patients using GLP-1a compared to patients on insulin treatment.

Molecular differences between cortical and trabecular bone, of relevance to understanding the pathophysiological basis of bone diseases, can be determined only through effective isolation methods for RNA and proteins. Here we present a TRIzol-based method, which combines bone pulverization and homogenization to extract simultaneously total RNA and proteins from human cortical and trabecular bone from the same carrot. RNA integrity and purity were determined as the 260/280 nm and 260/230 nm absorbance ratios and the 28S/18S rRNA ratio. Protein integrity and quality were evaluated by Coomassie blue staining. Reverse transcription quantitative polymerase chain reaction and immunoblotting for bone-specific genes and proteins were performed to verify the suitability of the isolated material in downstream applications. The 260/280 nm and 260/230 nm absorbance ratios were, on average, less than or equal to 1.8. Bands on agarose gel were consistent with intact RNA, with mean 28S/18S ratios of 1.68 ± 0.35 and 1.88 ± 0.10 for cortical and trabecular bone, respectively. Band patterns after Coomassie blue staining confirmed protein integrity. Successful gene and protein expression analysis, with relevant differences between the two compartments, highlighted the suitability of the material in downstream applications. The method presented here is appropriate and effective for the study of human bone.

Mouse models suggest that undercarboxylated osteocalcin (ucOC), produced by the skeleton, protects against type 2 diabetes development, whereas human studies have been inconclusive. We aimed to determine if ucOC or total OC is associated with incident type 2 diabetes or changes in fasting glucose, insulin resistance (HOMA-IR), or beta-cell function (HOMA-Beta). A subcohort (n = 338; 50% women; 36% black) was identified from participants without diabetes at baseline in the Health, Aging, and Body Composition Study. Cases of incident type 2 diabetes (n = 137) were defined as self-report at an annual follow-up visit, use of diabetes medication, or elevated fasting glucose during 8 years of follow-up. ucOC and total OC were measured in baseline serum. Using a case-cohort design, the association between biomarkers and incident type 2 diabetes was assessed using robust weighted Cox regression. In the subcohort, linear regression models analyzed the associations between biomarkers and changes in fasting glucose, HOMA-IR, and HOMA-Beta over 9 years. Higher levels of ucOC were not statistically associated with increased risk of incident type 2 diabetes (adjusted hazard ratio = 1.06 [95% confidence interval, 0.84-1.34] per 1 standard deviation [SD] increase in ucOC). Results for %ucOC and total OC were similar. Adjusted associations of ucOC, %ucOC, and total OC with changes in fasting glucose, HOMA-IR, and HOMA-Beta were modest and not statistically significant. We did not find evidence of an association of baseline undercarboxylated or total osteocalcin with risk of incident type 2 diabetes or with changes in glucose metabolism in older adults. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)