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Introduction: The effects of bariatric surgery on skeletal health raise many concerns. Trabecular bone score (TBS) is obtained through the analysis of lumbar spine dual X-ray absorptiometry (DXA) images and allows an indirect assessment of skeletal microarchitecture (MA). The aim of our study was to evaluate the changes in bone mineral density (BMD) and alterations in bone microarchitecture assessed by TBS in morbidly obese women undergoing Roux-en-Y gastric bypass (RYGB), over a three-year follow-up. Material/Methods: A prospective study of 38 morbidly obese white women, aged 46.3 ± 8.2 years, undergoing RYGB was conducted. Biochemical analyses and DXA scans with TBS evaluation were performed before and at one year and three years after surgery. Results: Patients showed normal calcium and phosphorus plasma concentrations throughout the study. However, 25-hydroxyvitamin D (25(OH)D3) decreased, and 71% of patients had a vitamin D deficiency at three years. BMD at femoral neck and lumbar spine (LSBMD) significantly decreased 13.53 ± 5.42% and 6.03 ± 6.79%, respectively, during the three-year follow-up; however Z-score values remained above those for women of the same age. TBS was within normal ranges at one and three years (1.431 ± 106 and 1.413 ± 85, respectively), and at the end of the study, 73.7% of patients had normal bone MA. TBS at three years correlated inversely with age (r = −0.41, p = 0.010), body fat (r = −0.465, p = 0.004) and greater body fat deposited in trunk (r = −0.48, p = 0.004), and positively with LSBMD (r = 0.433, p = 0.007), fat mass loss (r = 0.438, p = 0.007) and lean mass loss (r = 0.432, p = 0.008). In the regression analysis, TBS remained associated with body fat (β = −0.625, p = 0.031; R2 = 0.47). The fracture risk, calculated by FRAX® (University of Sheffield, Sheffield, UK), with and without adjustment by TBS, was low. Conclusion: Women undergoing RYGB in the mid-term have a preserved bone MA, assessed by TBS.

PurposeNivolumab is a monoclonal antibody that blocks the activation of programmed death-1 receptor, promoting T-cell activation against cancer cells. Thyroid dysfunction (TD) is a common immune-related adverse event (irAE) induced by nivolumab. We report the prevalence, patterns and outcomes of nivolumab-induced TD among cancer patients in our center.MethodsAll patients treated with nivolumab during 2016 were included. We assessed thyroid function tests, thyroid autoimmunity, thyroid imaging, and clinical outcome during nivolumab therapy as well as overall survival (OS).ResultsSeventy-three patients (55 with non-small-cell lung cancer [NSCLC], 9 with melanoma and 9 with Hodgkin lymphoma) were included. Median of follow up: 390.5 days. Seventeen patients (23.3%) developed TD during treatment. Thyrotoxicosis was reported in seven patients. Serum thyroid-stimulating hormone (TSH) nadir occurred after a median of 51 days (95% CI: 35–71). Thyroid antibodies were positive in three of the seven patients. Five of the seven hyperthyroid patients became hypothyroid later, and four of them required levothyroxine treatment. Primary hypothyroidism occurred in ten patients. Serum TSH peak occurred after a median of 110 days [95% CI: 85.2–197]. Thyroid autoimmunity was positive in one patient. In patients with NSCLC, TD was associated with better OS (HR = 0.4 [95% CI: 0.17–0.94]; p = 0.035).ConclusionsTD induced by nivolumab is a common and heterogeneous irAE. Thyrotoxicosis develops earlier than hypothyroidism. A pattern consistent with a transient thyroiditis followed by hypothyroidism was observed in one-third of patients. Our results suggest that patients with NSCLC and nivolumab-induced TD might have better survival.

Predicting which acromegaly patients could benefit from somatostatin receptor ligands (SRL) is a must for personalized medicine. Although many biomarkers linked to SRL response have been identified, there is no consensus criterion on how to assign this pharmacologic treatment according to biomarker levels. Our aim is to provide better predictive tools for an accurate acromegaly patient stratification regarding the ability to respond to SRL. We took advantage of a multicenter study of 71 acromegaly patients and we used advanced mathematical modelling to predict SRL response combining molecular and clinical information. Different models of patient stratification were obtained, with a much higher accuracy when the studied cohort is fragmented according to relevant clinical characteristics. Considering all the models, a patient stratification based on the extrasellar growth of the tumor, sex, age and the expression of E-cadherin, GHRL , IN1-GHRL , DRD2 , SSTR5 and PEBP1 is proposed, with accuracies that stand between 71 to 95%. In conclusion, the use of data mining could be very useful for implementation of personalized medicine in acromegaly through an interdisciplinary work between computer science, mathematics, biology and medicine. This new methodology opens a door to more precise and personalized medicine for acromegaly patients.

Background: This study aimed to evaluate the influence of maternal diabetes in the risk of neurodevelopmental disorders in offspring in the prenatal and postnatal periods.Methods: This cohort study included singleton gestational diabetes mellitus (GDM) pregnancies >22 weeks’ gestation with live newborns between 1991 and 2008. The control group was randomly selected and matched (1:2) for maternal age, weeks of gestation and birth year. Cox regression models estimated the effect of GDM on the risk of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and maternal type 2 diabetes mellitus (T2DM). Moreover, interaction between maternal T2DM and GDM-ADHD relationship was evaluated.Results: Children (n=3,123) were included (1,073 GDM; 2,050 control group). The median follow-up was 18.2 years (interquartile range, 14.2 to 22.3) (n=323 with ADHD, n=36 with ASD, and n=275 from women who developed T2DM). GDM exposure was associated with ADHD (hazard ratio [HR]crude, 1.67; 95% confidence interval [CI], 1.33 to 2.07) (HRadjusted, 1.64; 95% CI, 1.31 to 2.05). This association remained significant regardless of the treatment (diet or insulin) and diagnosis after 26 weeks of gestation. Children of mothers who developed T2DM presented higher rates of ADHD (14.2 vs. 10%, P=0.029). However, no interaction was found when T2DM was included in the GDM and ADHD models (P>0.05). GDM was not associated with an increased risk of ASD (HRadjusted, 1.46; 95% CI, 0.74 to 2.84).Conclusion: Prenatal exposure to GDM increases the risk of ADHD in offspring, regardless of GDM treatment complexity. However, postnatal exposure to maternal T2DM was not related to the development of ADHD.

Background: Sarcopenia and diabetes contribute to the development of frailty. Therefore, accessible methods, such as muscle ultrasounds (MUSs), to screen for sarcopenia should be implemented in clinical practice. Methods: We conducted a cross-sectional pilot study including 47 patients with diabetes (mean age: 77.72 ± 5.08 years, mean weight: 75.8 kg ± 15.89 kg, and body mass index: 31.19 ± 6.65 kg/m2) categorized as frail by the FRAIL Scale or Clinical Frailty Scale and confirmed by Fried’s Frailty Phenotype or Rockwood’s 36-item Frailty Index. We used the SARC-F questionnaire to identify sarcopenia. The Short Physical Performance Battery (SPPB) and the Timed Up and Go (TUG) tests were used to assess physical performance and the risk of falls, respectively. In addition, other variables were measured: fat-free mass (FFM) and Sarcopenia Risk Index (SRI) with the bioimpedance analysis (BIA); thigh muscle thickness (TMT) of the quadriceps with MUS; and hand-grip strength with dynamometry. Results: We observed correlations between the SARC-F and FFM (R = −0.4; p < 0.002) and hand-grip strength (R = −0.5; p < 0.0002), as well as between the TMT and FFM of the right leg (R = 0.4; p < 0.02) and the SRI (R = 0.6; p < 0.0001). We could predict sarcopenia using a logistic regression model with a ROC curve (AUC = 0.78) including FFM, handgrip strength, and TMT. The optimal cut-off point for maximum efficiency was 1.58 cm for TMT (sensitivity = 71.4% and specificity = 51.5%). However, we did not observe differences in the TMT among groups of greater/less frailty based on the SARC-F, SPPB, and TUG (p > 0.05). Conclusions: MUSs, which correlated with the BIA (R = 0.4; p < 0.02), complemented the diagnosis, identifying regional sarcopenia of the quadriceps in frail patients with diabetes and improving the ROC curve to AUC = 0.78. In addition, a TMT cut-off point for the diagnosis of sarcopenia of 1.58 cm was obtained. Larger studies to validate the MUS technique as a screening strategy are warranted.

Background/Objectives: Obesity is associated with cognitive decline, and metabolic bariatric surgery (MBS) can improve both physical and cognitive outcomes. However, cognitive improvements post-surgery are variable. This study explores the role of skeletal muscle health, specifically muscle strength and mass, in cognitive performance after MBS, aiming to identify factors that influence cognitive recovery. Methods: In this prospective study, 55 patients scheduled for MBS were assessed 1 month before and 12 months after surgery. Body composition, including appendicular lean mass (ALM) and fat mass, was measured using dual-energy X-ray absorptiometry (DXA). Handgrip strength (HGS) was assessed via dynamometry, and neurocognitive performance was evaluated using a standardized test battery. Results: Significant improvements in cognitive performance were observed at 12 months post-surgery in attention, memory, language, executive functions and overall cognitive performance. Regarding body composition, significant reductions were observed in fat mass and body mass index (BMI). A decrease in ALM and no changes in HGS were observed; however, when adjusted for body size, both showed an increase. Regression analysis identified baseline HGS, but not muscle mass, as a significant predictor of cognitive performance at 12 months post-surgery. Conclusions: MBS leads to significant improvements in cognitive function. Our results suggest that baseline HGS may play a role in predicting cognitive outcomes post-surgery, highlighting the need for comprehensive assessments of both physical and cognitive health in patients undergoing MBS. Further longitudinal studies are needed to explore causal relationships and the potential reversibility of cognitive deficits post-surgery.

Background/Objectives: To evaluate the long-term impact of a structured diabetic foot education program on major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs) in individuals with type 1 diabetes. Methods: Retrospective cohort study including 327 adults with type 1 diabetes who participated in a structured diabetic foot education program between 1990 and 2014. The program included 10 h of education focused on diabetes self-management and foot care. Participants were encouraged to attend annual refresher sessions. The primary outcomes were the first occurrence of MALE (major amputation or lower-limb revascularization) and MACE (non-fatal stroke, non-fatal myocardial infarction, or all-cause death). Cox proportional hazards models were used to assess associations between the number of educational programs (EPs) attended (1, 2–3, >3) and outcomes. Results: Participants attended a median of two EPs during a median follow-up of 26.3 years. Of the total number of events, 21 were MALEs (crude incidence of 1.9 per 1000 person-years) and 108 were MACEs (incidence of 12.9 per 1000 person-years). Risk of MALE was not associated with the number of EPs attended (p = 0.384). In contrast, participants who attended >3 EPs had a significantly lower risk of MACE compared with those attending only one program (HR 0.48, 95% CI 0.24–0.99, p = 0.044), although this association was attenuated after adjusting for smoking status. Conclusions: Frequent participation in a structured diabetic foot education program was associated with fewer cardiovascular events, but this benefit was diminished by smoking. Integrating tobacco cessation into education programs may enhance their long-term impact.

Acromegaly is caused by excess growth hormone (GH) produced by a pituitary tumor. First-generation somatostatin receptor ligands (SRLs) are the first-line treatment. Several studies have linked E-cadherin loss and epithelial-mesenchymal transition (EMT) with resistance to SRLs. Our aim was to study EMT and its relationship with SRLs resistance in GH-producing tumors. We analyzed the expression of EMT-related genes by RT-qPCR in 57 tumors. The postsurgical response to SRLs was categorized as complete response, partial response, or nonresponse if IGF-1 was normal, had decreased more than 30% without normalization, or neither of those, respectively. Most tumors showed a hybrid and variable EMT expression profile not specifically associated with SRL response instead of a defined epithelial or mesenchymal phenotype. However, high SNAI1 expression was related to invasive and SRL-nonresponsive tumors. RORC was overexpressed in tumors treated with SRLs before surgery, and this increased expression was more prominent in those cases that normalized postsurgical IGF-1 levels under SRL treatment. In conclusion, GH-producing tumors showed a heterogeneous expression pattern of EMT-related genes that would partly explain the heterogeneous response to SRLs. SNAI1 and RORC may be useful to predict response to SRLs and help medical treatment decision making.

Objectives: With the increasing prevalence of diabetes and frailty among older adults, there is an urgent need for precision medicine that incorporates comprehensive geriatric assessments, including frailty detection. This scoping review aims to map and synthesize the available evidence on validated tools for detecting pre-frailty and frailty in community-dwelling elderly individuals with diabetes and outpatient diabetes patients. Specifically, it addresses: (1) What validated tools are available for detecting pre-frailty and frailty in this population? (2) How are these tools associated with outcomes such as glycemic control, hypoglycemia, and metabolic phenotypes? (3) What gaps exist in the literature regarding these tools? Methods: The review followed PRISMA-ScR guidelines, conducting a systematic search across PubMed, Cochrane Library, and Web of Science. The inclusion criteria focused on studies involving individuals aged 70 years and older with diabetes, emphasizing tools with predictive capacity for disability and mortality. Results: Eight instruments met the inclusion criteria, including the Frailty Index, Physical Frailty Phenotype, and Clinical Frailty Scale. These tools varied in domains such as physical, psychological, and social aspects of frailty and their association with glycemic control, hypoglycemia, and metabolic phenotypes. The review identified significant gaps in predicting diabetes-related complications and their clinical application. Conclusions: Routine management of older adults with diabetes should incorporate frailty detection, as it is crucial for their overall health. Although widely used, the reviewed tools require refinement to address the unique characteristics of this population. Developing tailored instruments will enhance precision medicine, leading to more effective, individualized interventions for elderly individuals with diabetes.