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Objectives: Evaluate the prevalence of genetic factors in a large population of infertile subjects and define the seminological, hormonal, and ultrasonographic features for each alteration. Methods: This single-center retrospective study included male partners of infertile couples undergoing genetic investigations due to oligozoospermia or azoospermia evaluated from January 2012 to January 2022. The genetic investigations consist of karyotype, CFTR gene mutations plus variant of the IVS8-5T polymorphic trait, Y chromosome microdeletion, and Next Generation Sequencing panel to analyze genes implicated in congenital hypogonadotropic hypogonadism (CHH). Results: Overall, 15.4% (72/466) of patients received a diagnosis of genetic cause of infertility. Specifically, 23 patients (31.9%) harbor mutations in the CFTR gene, 22 (30.6%) have a 47, XXY karyotype, 14 (19.4%) patients show a Y chromosome microdeletion, 7 (9.7%) have structural chromosomal anomalies, and 6 (8.3%) have CHH. Overall, 80.6% of patients were azoospermic and 19.4% oligozoospermic (sperm concentration 3.5 ± 3.8 million/mL). Almost all patients presented hormonal alterations related to the specific genotype, while the main ultrasound alterations were testicular hypoplasia, calcifications/microcalcifications, and enlarged/hyperechoic epididymis. Conclusions: The prevalence of genetic abnormalities in males of infertile couples was 15.4% in our Center. CFTR gene disease-causing variants resulted in more frequent, with various clinical features, highlighting the complexity and heterogeneity of the presentation. Other investigations are needed to understand if conditions like ring chromosomes and other translocations are related to infertility or are incidental factors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the prevalence of DM among patients with ED and the impact of glycometabolic compensation and antihyperglycemic treatment on ED severity. Methods: In total, 1332 patients with ED were enrolled. The diagnosis was performed through the International-Index-of-Erectile-Function questionnaire. ED severity was considered according to presence/absence of spontaneous erections, maintenance/achievement deficiency and response to PDE5-i. DM patients were clustered according to antihyperglycemic treatment: "metformin"/"insulin"/"old antihyperglycemic drugs"/"new antihyperglycemic drugs". Results: The prevalence of DM patients was 15.8% (Group A, patients with ED and DM). Among these, the prevalence of spontaneous erections (21.0%) was lower than in the remaining patients (Group B, patients with ED without DM) (32.0%, p < 0.001). The prevalence of poor response to PDE5-i was lower in Group B (10.0%) than in Group A (35.0%, p < 0.001). Patients with good response to PDE5-i therapy showed lower HbA1c values than patients with poor/no response (6.6 ± 1.1% vs. 7.7 ± 1.9%, p = 0.02). The prevalence of absent response to PDE5-i was higher in patients treated with old antidiabetic drugs than in the population treated with new drugs (p = 0.03). Conclusion: The severity of ED and lower response to PDE5-i were higher in DM patients. A better glycometabolic profile, as well as new antihyperglycemic drugs, seem to have a positive effect on ED. [ABSTRACT FROM AUTHOR]

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/m2) 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/m2). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/m2. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Oxaliplatin-based chemotherapy remains the mainstay of first-line therapy in patients with metastatic colorectal cancer (mCRC). Unfortunately, only approximately 60% of treated patients achieve response, and half of responders will experience an early onset of disease progression. Furthermore, some individuals will develop a mixed response due to the emergence of resistant tumor subclones. The ability to predicting which patients will acquire resistance could help them avoid the unnecessary toxicity of oxaliplatin therapies. Furthermore, sorting out lesions that do not respond, in the context of an overall good response, could trigger further investigation into their mutational landscape, providing mechanistic insight towards the planning of a more comprehensive treatment. In this study, we validated a delta-radiomics signature capable of predicting response to oxaliplatin-based first-line treatment of individual liver colorectal cancer metastases. Findings could pave the way to a more personalized treatment of patients with mCRC. The purpose of this paper is to develop and validate a delta-radiomics score to predict the response of individual colorectal cancer liver metastases (lmCRC) to first-line FOLFOX chemotherapy. Three hundred one lmCRC were manually segmented on both CT performed at baseline and after the first cycle of first-line FOLFOX, and 107 radiomics features were computed by subtracting textural features of CT at baseline from those at timepoint 1 (TP1). LmCRC were classified as nonresponders (R−) if they showed progression of disease (PD), according to RECIST1.1, before 8 months, and as responders (R+), otherwise. After feature selection, we developed a decision tree statistical model trained using all lmCRC coming from one hospital. The final output was a delta-radiomics signature subsequently validated on an external dataset. Sensitivity, specificity, positive (PPV), and negative (NPV) predictive values in correctly classifying individual lesions were assessed on both datasets. Per-lesion sensitivity, specificity, PPV, and NPV were 99%, 94%, 95%, 99%, 85%, 92%, 90%, and 87%, respectively, in the training and validation datasets. The delta-radiomics signature was able to reliably predict R− lmCRC, which were wrongly classified by lesion RECIST as R+ at TP1, (93%, averaging training and validation set, versus 67% of RECIST). The delta-radiomics signature developed in this study can reliably predict the response of individual lmCRC to oxaliplatin-based chemotherapy. Lesions forecasted as poor or nonresponders by the signature could be further investigated, potentially paving the way to lesion-specific therapies. [ABSTRACT FROM AUTHOR]

While cross-sectional imaging has seen continuous progress and plays an undiscussed pivotal role in the diagnostic management and treatment planning of patients with rectal cancer, a largely unmet need remains for improved staging accuracy, assessment of treatment response and prediction of individual patient outcome. Moreover, the increasing availability of target therapies has called for developing reliable diagnostic tools for identifying potential responders and optimizing overall treatment strategy on a personalized basis. Radiomics has emerged as a promising, still fully evolving research topic, which could harness the power of modern computer technology to generate quantitative information from imaging datasets based on advanced data-driven biomathematical models, potentially providing an added value to conventional imaging for improved patient management. The present study aimed to illustrate the contribution that current radiomics methods applied to magnetic resonance imaging can offer to managing patients with rectal cancer. [ABSTRACT FROM AUTHOR]