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Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection.

Diabetic neuropathy (DN) is one of the main microvascular complications of both type 1 and type 2 diabetes mellitus. Sometimes, this could already be present at the time of diagnosis for type 2 diabetes mellitus (T2DM), while it appears in subjects with type 1 diabetes mellitus (T1DM) almost 10 years after the onset of the disease. The impairment can involve both somatic fibers of the peripheral nervous system, with sensory-motor manifestations, as well as the autonomic system, with neurovegetative multiorgan manifestations through an impairment of sympathetic/parasympathetic conduction. It seems that, both indirectly and directly, the hyperglycemic state and oxygen delivery reduction through the vasa nervorum can determine inflammatory damage, which in turn is responsible for the alteration of the activity of the nerves. The symptoms and signs are therefore various, although symmetrical painful somatic neuropathy at the level of the lower limbs seems the most frequent manifestation. The pathophysiological aspects underlying the onset and progression of DN are not entirely clear. The purpose of this review is to shed light on the most recent discoveries in the pathophysiological and diagnostic fields concerning this complex and frequent complication of diabetes mellitus.

Cardiac hypertrophy develops in response to increased workload to reduce ventricular wall stress and maintain function and efficiency. Pathological hypertrophy can be adaptive at the beginning. However, if the stimulus persists, it may progress to ventricular chamber dilatation, contractile dysfunction, and heart failure, resulting in poorer outcome and increased social burden. The main pathophysiological mechanisms of pathological hypertrophy are cell death, fibrosis, mitochondrial dysfunction, dysregulation of Ca2+-handling proteins, metabolic changes, fetal gene expression reactivation, impaired protein and mitochondrial quality control, altered sarcomere structure, and inadequate angiogenesis. Diabetic cardiomyopathy is a condition in which cardiac pathological hypertrophy mainly develop due to insulin resistance and subsequent hyperglycaemia, associated with altered fatty acid metabolism, altered calcium homeostasis and inflammation. In this review, we summarize the underlying molecular mechanisms of pathological hypertrophy development and progression, which can be applied in the development of future novel therapeutic strategies in both reversal and prevention.

Diabetic patients are frequently affected by coronary microvascular dysfunction (CMD), a condition consisting of a combination of altered vasomotion and long-term structural change to coronary arterioles leading to impaired regulation of blood flow in response to changing cardiomyocyte oxygen requirements. The pathogenesis of this microvascular complication is complex and not completely known, involving several alterations among which hyperglycemia and insulin resistance play particularly central roles leading to oxidative stress, inflammatory activation and altered barrier function of endothelium. CMD significantly contributes to cardiac events such as angina or infarction without obstructive coronary artery disease, as well as heart failure, especially the phenotype associated with preserved ejection fraction, which greatly impact cardiovascular (CV) prognosis. To date, no treatments specifically target this vascular damage, but recent experimental studies and some clinical investigations have produced data in favor of potential beneficial effects on coronary micro vessels caused by two classes of glucose-lowering drugs: glucagon-like peptide 1 (GLP-1)-based therapy and inhibitors of sodium-glucose cotransporter-2 (SGLT2). The purpose of this review is to describe pathophysiological mechanisms, clinical manifestations of CMD with particular reference to diabetes, and to summarize the protective effects of antidiabetic drugs on the myocardial microvascular compartment.

Background Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels. Methods Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale. Results Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8–38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients. Conclusions Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.

Background and Objectives: With the increasing life expectancy, the frequency of total thyroidectomies in elderly patients has risen, raising concerns regarding hemorrhage and recurrent laryngeal nerve palsy compared to the general population. Therefore, considering the frequent alteration of the coagulation status in such patients, innovative methods able to reach an accurate hemostasis appear highly desirable. This retrospective multicentric study aimed to compare the postoperative outcomes of patients treated with conventional hemostasis with patients treated with the Harmonic Scalpel (HS) and gelatin–thrombin matrix (Floseal). Materials and Methods: Patients undergoing total thyroidectomy were retrospectively enrolled and categorized into two groups: Group A patients underwent surgery with the Harmonic Scalpel and Floseal, while Group B underwent traditional hemostasis surgery with ligations and monopolar electrocautery. The primary endpoint was the drain output after 24 and 48 h and the presence of significant blood loss. Secondary endpoints included the presence of seroma, wound infection, hematoma, laryngeal nerve palsy, surgery duration, and onset of post-surgical hypocalcemia. Results: From January 2014 to January 2024, 870 individuals participated in the study. Group A (gelatin–thrombin and HS) comprised 502 patients, while Group B (Standard Hemostasis—control group) comprised 368 patients. The 24 h drain output was 52 ± 25 mL in Group A vs. 113 ± 27 mL in Group B, p = 0.003, while the 48 h drain output was 95 ± 29 mL in Group A and 113 ± 27 mL in Group B (p = 0.002). Significant blood loss occurred in eight patients (2.2%) of Group B vs. three cases (0.6%) in Group A (p = 0.039). Also, neck hematoma (p = 0.012), seroma (p = 0.005), and reoperation (p = 0.052) values were significantly lower in Group A. Conclusions: Surgery aided with HS, and gelatin–thrombin was associated with lower major and minor complications compared to the conventional approach, guarantying reduced operative time, ensuring hemostasis, and preserving parathyroid glands, even in elderly patients.

Background Diaphragmatic hernia (DH) presenting acutely can be a potentially life-threatening condition. Its management continues to be debatable. Methods A bibliographic search using major databases was performed using the terms “emergency surgery” “diaphragmatic hernia,” “traumatic diaphragmatic rupture” and “congenital diaphragmatic hernia.” GRADE methodology was used to evaluate the evidence and give recommendations. Results CT scan of the chest and abdomen is the diagnostic gold standard to evaluate complicated DH. Appropriate preoperative assessment and prompt surgical intervention are important for a clinical success. Complicated DH repair is best performed via the use of biological and bioabsorbable meshes which have proven to reduce recurrence. The laparoscopic approach is the preferred technique in hemodynamically stable patients without significant comorbidities because it facilitates early diagnosis of small diaphragmatic injuries from traumatic wounds in the thoraco-abdominal area and reduces postoperative complications. Open surgery should be reserved for situations when skills and equipment for laparoscopy are not available, where exploratory laparotomy is needed, or if the patient is hemodynamically unstable. Damage Control Surgery is an option in the management of critical and unstable patients. Conclusions Complicated diaphragmatic hernia is a rare life-threatening condition. CT scan of the chest and abdomen is the gold standard for diagnosing the diaphragmatic hernia. Laparoscopic repair is the best treatment option for stable patients with complicated diaphragmatic hernias. Open repair is considered necessary in majority of unstable patients in whom Damage Control Surgery can be life-saving.

Background Prophylactic central neck lymph-nodes dissection is still a topic of major debate in Literature. There is a lack of randomized controlled trials proving advantages in its application in terms of overall survival and local recurrence. Due to the recent rapid increase of elderly population, differentiated tumor carcinoma diagnosis increased in patients over 65 years old. The aim of this study was to compare recurrence rate, complications rate and histological features of tumors in elderly population. Methods A retrospective study was carried out collecting data from 371 patients with differentiated thyroid cancer without clinical evidence of lymph-nodes involvement in three Italian referral centers from 2005 to 2015. All patients were aged ≥ 65 years and were divided in two groups based on the performed surgery (total thyroidectomy alone or associated with central lymph-nodes dissection). Moreover, patients were stratified according to the age between 65 and 74 years old and over 75 years old. Results Total thyroidectomy alone was performed in 184 patients (group A) and total thyroidectomy with prophylactic central neck dissection was performed in 187 cases (group B). There was a statistically significant difference in complications between the groups in terms of neck hematoma (0.5% group A vs 3.7% group B), temporary hypoparathyroidism (11.4% group A vs 21.4% group B), and temporary unilateral recurrent nerve injury (1.5% group A vs 6.4% group B). Lymph nodes recurrence rate was 9.2% in group A and 8.5% in group B, with no statistically significant difference. There was a statistically significant difference in patients over 75 years old in terms of temporary hypoparathyroidism (24% group A vs 11% group B), permanent hypoparathyroidism (2,7% group A vs 0,3% group B) and recurrent nerve injury (9,5% group A vs 2% group B). Conclusions The role of prophylactic central neck dissection is still controversial, especially in elderly patients, and an aggressive surgical approach should be carefully evaluated. The Authors reported a similar low recurrence rate between total thyroidectomy and total thyroidectomy associated with prophylactic central neck dissection, with increased postoperative complications in the lymphadenectomy group and in patients over 75 years old, advocating a tailored surgical approach in elderly population.

Background: Schwannomas, also called neurinomas, are rare benign tumors of the neural cells that can develop from the sheaths of nervous structures of several districts, although the most frequent sites are the cranial nerves (25%–45%). Rarely, cases show neck schwannomas in the thyroid parenchyma, while the cases of thyroid-bed schwannomas mimicking a thyroid-gland lesions are anecdotal. Methods: We report the case of a 70-year-old man with a preoperative-imaging diagnosis of a thyroid neoplasm, confirmed as Thyr 4 by fine-needle cytology. Results: During surgery, an extra-thyroidal lesion was discovered, determined to be a neck schwannoma through definitive pathology. A literature review of cases of thyroid-bed-lesion schwannomas misinterpreted as thyroid neoplasms was carried out. Conclusions: In the case of suspicious extra-thyroidal lesions, we advocate for a close routine cooperation between the cytologist, the radiologist, and the surgeon in the attempt to reach an accurate preoperative diagnosis.

Objectives Bilateral recurrent nerve damage still represents one of the main complications following thyroid surgery, even though the nerve intraoperative monitoring has allowed the decrease of this injury. This observational retrospective study aims to define the onset modalities and the recovery time of different clinical conditions that may occurs after thyroidectomy. Methods From a total of 1417 patients who underwent total thyroidectomy for benign tumors between 2017 and 2022 in ENT Unit of University of Campania “L. Vanvitelli,” this study involved 30 patients with bilateral vocal folds motility deficit. These patients (28 F, 2 M), aged from 24 to 78 years old (average age 51.7), presented a bilateral vocal fold motility deficit. Five patients of the study developed an acute respiratory failure upon the awakening that required a nasotracheal prolonged safe extubation. The other 25 patients underwent 9 months diagnostic and therapeutic process, which started approximately 30 days after thyroid surgery. Results Indeed, there are several outcomes of these complications, like functional laryngeal defects, which are mainly related to respiratory and phonatory activities. These clinical manifestations can evolve in different ways within a context of a wide range of possibilities, from the spontaneous bilateral or monolateral recovery to the necessity of a functional or surgical restoration. Conclusion This study allowed the acquisition of useful information about prognostic indications and an adequate therapeutic process, based on the specific clinical characteristics.