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Background and Objectives : Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. Materials and Methods : This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The methodology involved detailed assessments including Sudoscan tests to evaluate sudomotor function and various cardiovascular reflex tests (CART). The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. Results : The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. Conclusions : On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

Chronic kidney disease (CKD) represents a significant public health issue, particularly prevalent among patients with type 2 diabetes mellitus (T2DM). CKD occurs in approximately 20% to 40% of adults with diabetes mellitus. Sudoscan potentially detects CKD early, providing a non-invasive and convenient alternative to traditional screening methods that rely on serum creatinine and urine albumin levels. This research involves 271 patients from a single medical center over one year, with all participants providing informed consent. The prevalence of CKD in our group was 26.5% ( n = 72). This study integrates a comprehensive examination, including anthropometric measurements, biochemical profiles, and Sudoscan's electrochemical skin conductance testing. CKD diagnosis was confirmed via estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). The aim of this study was to explore the utility of Sudoscan in detecting CKD among patients with T2DM. Statistical analysis reveals moderate correlations between Sudoscan scores and traditional CKD markers like eGFR and albuminuria. It is beneficial in settings where conventional testing is less accessible, suggesting potential for broader CKD screening programs. Key findings suggest that Sudoscan can identify early renal dysfunction with reasonable sensitivity and specificity. Integrating Sudoscan in regular CKD screening could enhance early detection, allowing for timely interventions to prevent progression to end-stage renal disease and reduce healthcare burdens associated with advanced CKD. The results contribute to the ongoing assessment of innovative technologies in managing chronic diseases related to diabetes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Nica et al.)

Introduction:  Cardiac autonomic neuropathy (CAN) is a disorder affecting the autonomic nerves that regulate the cardiovascular system, leading to irregular heart rate and blood pressure control. It is commonly associated with diabetes mellitus but can also result from other conditions such as autoimmune disorders, chronic kidney disease, alcohol abuse, and certain medications. Screening for CAN is essential, particularly in individuals with poor glycemic control, cardiovascular risk factors, or complications. Early identification of CAN is vital for timely intervention to prevent or manage cardiovascular complications effectively. Regular screening helps detect CAN before symptoms emerge, enabling early intervention to slow or halt its progression. This study examined the relationship between sudomotor function and cardiovascular reflex tests., Material and Methods:  This was a cross-sectional study conducted between June 2019 and June 2020. The study included 271 subjects aged 18 years and above who provided informed consent, were diagnosed with type 2 diabetes mellitus (T2DM), and were overweight or obese. Exclusion criteria encompassed patients with other types of diabetes, pregnant women, those with recent neoplasm diagnoses, stroke sequelae, history of myocardial infarction, or pelvic limb amputations. The assessment of cardiac autonomic neuropathy involved conducting an electrocardiogram and evaluating the QTc interval in the morning before taking medication. Additionally, cardiovascular reflex tests (CART) were conducted, including assessments of heart rate variability during deep breathing, the Valsalva maneuver, and changes in orthostatic position. Simultaneously, the diagnosis of CAN was assessed by performing a sweat test using a Sudoscan assessment (Impeto Medical, Moulineaux, France).  Results: More than half of the participants (52%, n=143) were female. Significant differences in statistical measures were noted between females and males regarding age, systolic blood pressure, fasting blood glucose, A1c level, total cholesterol, triglycerides, gamma-glutamyl transferase, and bilirubin levels. Within the CAN-diagnosed group (CAN+), 40.92% were classified as mild cases (n=90), 47.27% as moderate cases (n=104), and 11.81% as severe cases (n=26). Among the CAN+ group, 54% (n=119) were women. Electrochemical skin conductance was lower in the CAN+ group than the CAN- group in hands (67.34±15.51 μS versus 72.38±12.12 μS, p=0.008) and feet (73.37±13.38 μS versus 82.84 ±10.29 μS, p<0.001). The Sudoscan-CAN score significantly correlated with Ewing scores (r= 0.522, p<0.001). In multiple linear regression analysis, the Sudoscan-CAN score remained significantly associated with age, high BMI, long-standing diabetes, and Ewing score., Conclusions:   Sudoscan demonstrates potential in identifying patients with an increased risk of CAN. Its integration into clinical practice can improve patient outcomes through early detection, risk stratification, and personalized treatment approaches. Its non-invasive, portable, and user-friendly features render it suitable for utilization in outreach programs or resource-constrained settings as part of screening efforts designed to pinpoint high-risk individuals for additional assessment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Nica et al.)

Pancreatic heterotopy is a rare entity defined as the presence of abnormally located pancreatic tissue without any anatomical or vascular connection to the normal pancreas. Heterotopic pancreatic tissue can be found in various regions of the digestive system, such as the stomach, duodenum, and upper jejunum, with the less commonly reported location being the gallbladder. Gallbladder pancreatic heterotopia can be either an incidental finding or diagnosed in association with cholecystitis. Pancreatitis of the ectopic tissue has also been described. In this context, we report three cases of heterotopic pancreatic tissue in the gallbladder with different types of pancreatic tissue according to the Heinrich classification. One patient was a 24-year-old male who presented with acute pancreatitis symptoms and an ultrasonographical detected mass in the gallbladder, which proved to be heterotopic pancreatic tissue. The other two cases were female patients aged 24 and 32, respectively, incidentally diagnosed on histopathological examination after cholecystectomy for symptomatic cholelithiasis. Both cases displayed chronic cholecystitis lesions; one of them was also associated with low grade dysplasia of the gallbladder. Although a rare occurrence in general, pancreatic heterotopia should be acknowledged as a possible incidental finding in asymptomatic patients as well as a cause for acute cholecystitis or pancreatitis.

The piriformis syndrome is one of the most commonly misdiagnosed causes of lower back and gluteal pain caused by the compression of the sciatic nerve and the internal pudendal neurovascular bundle by the piriformis muscle. Although this syndrome was first suggested over 90 years ago, its diagnosis still represents a challenge for clinicians. In the present study, dissection was used to determine the intra- and extrapelvic anatomical course of the internal pudendal nerve and the data were compared with the information obtainable through MRI examination, in order to identify the piriformis syndrome and to differentiate it from other causes of internal pudendal neuralgia. Thorough dissections of the pelvis and deep gluteal region were conducted on female cadavers, which were correlated with MRI scans, in order to describe the course of the internal pudendal nerve in contact with the piriformis muscle. The dissection findings and MRI scans obtained allowed us to describe and demonstrate the compression points along the course of the sciatic nerve and the internal pudendal bundle, the anatomical correlations between the piriformis muscle and the nervous structures around it, emphasizing the areas most susceptible to possible nerve impingement syndromes. In the anatomic trajectory of the sciatic nerve and the internal pudendal bundle there are multiple contact points with anatomical structures that may lead to compression of the nerve structures, generating symptoms that comprise the piriformis syndrome. The present study sought to establish clear osseous landmarks that may help evaluate these associations and possible nerve compressions on pelvic MRI examination., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Goidescu et al.)

As diabetes prevalence is continuously increasing, better management is needed to achieve blood glucose control, in order to prevent complications and lessen the burden of this disease. Since the first measurement of glycosuria at the beginning of the 1900s', huge advances were made in monitoring glycemia. Continuous glucose monitoring systems revolutionized diabetes management, especially for patients with type 1 diabetes. Avoiding glycemic variability and maintaining optimal glycemic control is crucial for the evolution of patients with type 1 diabetes. The usefulness of glycemic monitoring devices can be extended to patients with type 2 diabetes. It is also important to note that in those patients at risk of developing high glycemic variability (e.g. patients with advanced chronic kidney disease), continuous glycemic monitoring may improve their prognosis. These monitoring systems can be classified according to the analytical method, the degree of invasiveness, the data availability and the mode of usage. The technology is constantly improving in bioanalytical performance, biocompatibility, length of wearing time, safety and clinical features. The aim of this review was to briefly present the main characteristics of glucose biosensors, glucose monitoring systems and their clinically utility., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Mihai et al.)

Renal cell carcinoma (RCC) accounts for over 90% of all renal malignancies, and mainly affects the male population. Obesity and smoking are involved in the pathogenesis of several systemic cancers including RCC. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway regulates cell growth, differentiation, migration, survival, angiogenesis, and metabolism. Growth factors, hormones, cytokine and many extracellular cues activate PI3K/AKT/mTOR. Dysregulation of this molecular pathway is frequently reported in human cancers including RCC and is associated with aggressive development and poor survival rate. mTOR is the master regulator of cell metabolism and growth, and is activated in many pathological processes such as tumour formation, insulin resistance and angiogenesis. mTOR inhibitors are used at present as drug therapy for RCC to inhibit cell proliferation, growth, survival, and the cell cycle. Temsirolimus and everolimus are two mTOR inhibitors that are currently used for the treatment of RCC. Drugs targeting the PI3K/AKT/mTOR signalling pathway may be one of the best therapeutic options for RCC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Miricescu et al.)

Obesity is a worldwide pandemic health issue. Obesity is associated with the pathogenesis of type 2 diabetes, hypertension, dyslipidemia, cardiovascular diseases, cancer, and kidney diseases. This systemic disease can affect the kidneys by two mechanisms: Indirectly through diabetes mellitus (DM) and hypertension and directly through adipokines secreted by adipose tissue. Obesity is a risk factor for chronic kidney disease (CKD), which is associated with an increased risk of morbidity and mortality among the adult population. Increased visceral adipose tissue leads to renal glomerular hyperfiltration and hyperperfusion, which may lead to glomerular hypertrophy, proteinuria, and CKD development. Adipokines are hormones produced by fat tissue. They are involved in energy homeostasis, sugar and fat metabolism, reproduction, immunity, and thermogenesis control. Hormones and cytokines secreted by adipose tissue contribute to the development and progression of CKD. Decreased serum or urinary adiponectin levels are specific in diabetic and non-diabetic CKD patients, while leptin presents increased levels, and both are associated with the development of glomerulopathy. Excessive adipose tissue is associated with inflammation, oxidative stress (OS), insulin resistance and activation of the renin angiotensin-aldosterone system (RAAS). Therefore, adipose tissue dysfunction plays an important role in the development of CKD., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Miricescu et al.)

The cingulate cortex is part of the limbic system. Its function and connectivity are organized in a rostro-caudal and ventral-dorsal manner which was addressed by various other studies using rather coarse cortical parcellations. In this study, we aim at describing its function and connectivity using invasive recordings from patients explored for focal drug-resistant epilepsy. We included patients that underwent stereo-electroencephalographic recordings using intracranial electrodes in the University Emergency Hospital Bucharest between 2012 and 2019. We reviewed all high frequency stimulations (50 ​Hz) performed for functional mapping of the cingulate cortex. We used two methods to characterize brain connectivity. Effective connectivity was inferred based on the analysis of cortico-cortical potentials (CCEPs) evoked by single pulse electrical stimulation (SPES) (15 ​s inter-pulse interval). Functional connectivity was estimated using the non-linear regression method applied to 60 ​s spontaneous electrical brain signal intervals. The effective (stimulation-evoked) and functional (non-evoked) connectivity analyses highlight brain networks in a different way. While non-evoked connectivity evidences areas having related activity, often in close proximity to each other, evoked connectivity highlights spatially extended networks. To highlight in a comprehensive way the cingulate cortex's network, we have performed a bi-modal connectivity analysis that combines the resting-state broadband h 2 non-linear correlation with cortico-cortical evoked potentials. We co-registered the patient's anatomy with the fsaverage FreeSurfer template to perform the automatic labeling based on HCP-MMP parcellation. At a group level, connectivity was estimated by averaging responses over stimulated/recorded or recorded sites in each pair of parcels. Finally, for multiple regions that evoked a clinical response during high frequency stimulation, we combined the connectivity of individual pairs using maximum intensity projection. Connectivity was assessed by applying SPES on 2094 contact pairs and recording CCEPs on 3580 contacts out of 8582 contacts of 660 electrodes implanted in 47 patients. Clinical responses elicited by high frequency stimulations in 107 sites (pairs of contacts) located in the cingulate cortex were divided in 10 groups: affective, motor behavior, motor elementary, versive, speech, vestibular, autonomic, somatosensory, visual and changes in body perception. Anterior cingulate cortex was shown to be connected to the mesial temporal, orbitofrontal and prefrontal cortex. In the middle cingulate cortex, we located affective, motor behavior in the anterior region, and elementary motor and somatosensory in the posterior part. This region is connected to the prefrontal, premotor and primary motor network. Finally, the posterior cingulate was shown to be connected with the visual areas, mesial and lateral parietal and temporal cortex., Competing Interests: Declaration of competing interest Andrei Barborica PhD is also Vice-President and Chief Technological Officer of FHC Inc, the manufacturer of the electrical stimulator and stereotactic fixture used in Bucharest. The other authors have nothing to disclose in relation to this work., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Starting from a typical case, we try to highlight the main critical elements, both in the diagnostic algorithm and in the therapeutic one. We hereby present a 54-year old patient, known with hepatic steatosis and renal microlithiasis, which undergoes an ultrasonography in ambulatory, on the background of unsystematised abdominal discomfort; the ultrasound reveals the presence of a tumoral mass in the right iliac fossa., (Celsius.)

Steadily, cancer is becoming the first cause of mortality, with over 9 million deaths estimated in 2018. Increasing evidence supports a direct association between obesity, type 2 diabetes mellitus (T2DM) and cancer, with a higher risk of cancer mortality especially for some of the most common malignancies, such as breast, colon, and rectal cancers. So far, several mechanisms underlying the cancer-diabetes relationship have been investigated revealing dysregulations of the insulin-insulin-like growth factor (IGF) system as the most important paradigm. Other molecular mechanisms that seem to play a role in the association cancer-T2DM consist of alteration of the signaling pathways activated by inflammatory cytokines, adipocytokines or adhesion molecules. The overall aim of this review is to provide an overview of the molecular mechanisms linking obesity, T2DM and cancer, as related to the receptors and signaling pathways involved in these associations.

Melanomas can exhibit a wide range of unusual morphologies due to the neural crest origin of melanocytes. Several authors have documented variations in size and shape of cells, cytoplasmic features and inclusions, nuclear features and cell architecture. Metastatic melanoma with rhabdomyoblastic differentiation is an extremely rare condition with poor prognosis. Few studies concerning rhabdoid or rhabdomyoblastic differentiation in melanoma are currently available and the current report highlights some of the most important immunohistochemical features of this rare entity. We report on a case of a rhabdomyoblastic metastatic melanoma showing intense positivity for both melanocytic and rhabdoid markers in two cell populations dissociated within the tumor with multiple mismatches in immunomarker expression. Improved recognition of this rare morphological pattern may provide the means for developing new techniques to identify novel therapeutic targets, which would improve the prognostic outlook for these patients.

Basal cell carcinoma (BCC) represents the most common skin malignancy, which has been linked over time to multifactorial causes. It usually occurs on sun-exposed areas in people with fair skin and with predilection for men. BCC usually affects elderly patients and has an extremely wide range of histological subtypes, which can present clinically under different variants, some with really challenging differentials. Although BCC may occur in familial settings, such as nevoid BCC syndrome, Rombo or Bazex-Dupré-Christol syndromes, nonsyndromic multiple BCCs have also been described in the scientific literature. In this review, we discuss in detail the latest scientific concepts regarding BCC, its etiology, pathogenesis, genetic bases of disease, morphology and immunophenotype, as well as the currently known genetic syndromes, which may lead to development of multiple BCCs, especially in young adults.

Conventional schwannoma represents a benign peripheral nerve sheath tumor derived from Schwann cells, which usually arises in the fourth or fifth decade of life, in the subcutaneous tissue of the distal extremities, or in the head and neck region of adult patients, with no gender predilection. In addition to the classic type, at least 11 different histopathological subtypes have been described and unawareness of these uncommon histopathological entities may lead to diagnostic pitfalls and risk of mistreatment. Recently described in the scientific literature, microcystic/reticular schwannoma is still relatively unknown to both surgeons and pathologists. The purpose of this paper is to highlight its existence by describing an additional case that occurred in the retroauricular area, and to further characterize its clinical, histopathological and immunohistochemical features. We reviewed the literature and compared the current case with others that have been documented thus far, discussing all possible differential diagnoses.

Extra Musculoskeletal manifestations are a distinct clinical entity that refers to a combination of clinical features, which are found in multiple rheumatic diseases. Besides the standard manifestations, other organs can be damaged such as the vascular system, skin, gastrointestinal tract, musculoskeletal system, cardiopulmonary system, hematologic system, kidneys, and the central nervous system. Among the gastrointestinal MCTD symptoms, the most frequent are the esophageal ones. Treatment of patients with MCTD must be performed by both medical and surgical multidisciplinary teams in order to provide a management suitable for the patients' needs. All authors have contributed significantly and have been involved in the writing of the manuscript in draft and any revision stages, and have read and approved its final version.