GATA3 and TGF-ß in normal placenta and pre-eclampsia.

GATA3 plays critical roles in the development and function of various tissues and organs throughout the body. Likewise, TGF-ß signaling is critical for placental development and can interact with GATA3. We aimed to investigate the involvement of the multifunctional cytokine and transcription factor in trophoblast development. By using immunohistochemistry, we evaluated the localization and expression level of GATA3 and TGF-ß in placentas at term of normal pregnancy and with pre-eclampsia. Up-regulation of both GATA3 and TGF-ß was observed in pathological placentas, with localization in the villus epithelium (syncytiotrophoblast) stroma and decidua. Our data show altered expression of TGF-ß and GATA3, which downstream could lead to a cascade of events that negatively influence trophoblast development and contribute to the pathogenesis of pre-eclampsia.

Contrast-Enhanced Ultrasound as a Diagnostic Procedure in Renal Diseases: A Case Report.

Standard ultrasound (US) finds wide use in renal diseases as a screening procedure, but it is not always able to characterize lesions, especially in differential diagnosis between benign and malignant lesions. In contrast, contrast-enhanced ultrasonography (CEUS) is appropriate in differentiating between solid and cystic lesions as well as between tumors and pseudotumors. We show the case of a nephropathic patient who showed a complex, large, growing renal mass, characterized through a CEUS. This seventy-five-year-old diabetic heart patient showed a 6 cm-complex and plurisected cyst on ultrasound of left kidney. Laboratory data showed the presence of stage IIIb chronic renal failure with GFR 30 ml/min, creatinine 2.33 mg/dl, azotemia 88 mg/dl. The patient performed abdominal CT without contrast medium, showing at the level of the left upper pole, a roundish formation with the dimensions of approximately 70x53x50 mm. At the semiannual checkup, the nephrology examination showed a slight rise in creatinine and, therefore, after six months, it was decided to perform a CT scan without contrast medium again. CT showed a slight increase in the size of the mass located at the left kidney (74x56x57 mm). Given the increased size of the left mass, albeit modest, a CEUS was performed to reach a diriment diagnosis. CEUS concluded for complex cystic formation with presence of intraluminal solid-corpuscular material, with thrombotic-hemorrhagic etiology, in progressive phase of organization, classifiable as Bosniak type II cyst. CEUS in the kidneys is a cost-effective and valuable imaging technique; it is accurate in the characterization of indeterminate lesions and complex cysts.

Prediabetes Increases the Risk of Frailty in Older Adults With Prefrail Hypertension: Beneficial Effects of Metformin.

BACKGROUND: Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and frailty among older individuals. METHODS: We screened elders with prefrail hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months. RESULTS: We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r, 0.880; P<0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r, 0.809; P<0.0001). Prediabetes was found to significantly (P<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (P<0.0001). CONCLUSIONS: Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.

The relationship between muscle strength and epicardial fat in healthy adults.

BACKGROUND: Muscular strength and muscle mass are considered key factors for healthy ageing. Modification of body composition and redistribution of adipose tissue has been described in advanced age. Muscle strength has an important predictive role for health outcomes. However, little is known regarding the relationship between muscle strength and epicardial fat. METHODS AND MATERIALS: In a cohort of healthy adults following physical capacity evaluations, anthropometric measurements, handgrip strength (HGS), echocardiography and bioimpedance analysis (BIA) were performed. Kruskal-Wallis test, Spearman's correlation and regression analysis adjusted for confounders were applied. RESULTS: A total population of 226 adults, age range 18-83 years, were included. Epicardial fat thickness resulted significantly associated with age p < 0.001, HGS (p < 0.001). Regression analysis adjusted for confounders revealed an independent relationship between handgrip strength and epicardial fat thickness: regression coefficient: -1.34; R2 = 0.27 and p = 0.044. CONCLUSIONS: The relationship between epicardial fat and muscle strength is inverse and independent. Implementation of HGS measurement may be useful for the identification of subjects with excessive epicardial fat and cardiovascular risk. Measurement of epicardial fat could be helpful in the early detection of physical decline associated to ageing.

Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age.

Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamatergic transmission can be mediated by ionotropic glutamate receptors (iGluRs), which mediate rapid synaptic depolarization that can be associated with Ca2+ entry and activity-dependent change in the strength of synaptic transmission, as well as by metabotropic glutamate receptors (mGluRs), which mediate slower postsynaptic responses through the recruitment of second messenger systems. A wealth of evidence reported over the last three decades has shown that this dogmatic subdivision between iGluRs and mGluRs may not reflect the actual physiological signaling mode of the iGluRs, i.e., α-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid (AMPA) receptors (AMPAR), kainate receptors (KARs), and N-methyl-D-aspartate (NMDA) receptors (NMDARs). Herein, we review the evidence available supporting the notion that the canonical iGluRs can recruit flux-independent signaling pathways not only in neurons, but also in brain astrocytes and cerebrovascular endothelial cells. Understanding the signaling versatility of iGluRs can exert a profound impact on our understanding of glutamatergic synapses. Furthermore, it may shed light on novel neuroprotective strategies against brain disorders.

Frail hypertensive older adults with prediabetes and chronic kidney disease: insights on organ damage and cognitive performance - preliminary results from the CARYATID study.

BACKGROUND: Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR). METHODS: We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min. RESULTS: 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable. CONCLUSIONS: Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.

Current use of artificial intelligence in the diagnosis and management of acute appendicitis.

INTRODUCTION: Acute appendicitis is a common and time-sensitive surgical emergency, requiring rapid and accurate diagnosis and management to prevent complications. Artificial intelligence (AI) has emerged as a transformative tool in healthcare, offering significant potential to improve the diagnosis and management of acute appendicitis. This review provides an overview of the evolving role of AI in the diagnosis and management of acute appendicitis, highlighting its benefits, challenges, and future perspectives. EVIDENCE ACQUISITION: We performed a literature search on articles published from 2018 to September 2023. We included only original articles. EVIDENCE SYNTHESIS: Overall, 121 studies were examined. We included 32 studies: 23 studies addressed the diagnosis, five the differentiation between complicated and uncomplicated appendicitis, and 4 studies the management of acute appendicitis. CONCLUSIONS: AI is poised to revolutionize the diagnosis and management of acute appendicitis by improving accuracy, speed and consistency. It could potentially reduce healthcare costs. As AI technologies continue to evolve, further research and collaboration are needed to fully realize their potential in the diagnosis and management of acute appendicitis.

Robotic versus open resection for colorectal liver metastases in a "referral centre Hub&Spoke learning program". A multicenter propensity score matching analysis of perioperative outcomes.

Background: Surgical resection is still considered the optimal treatment for colorectal liver metastasis (CRLM). Although laparoscopic and robotic surgery demonstrated their reliability especially in referral centers, the comparison between perioperative outcomes of robotic liver resection (RLR) and open (OLR) liver resection are still debated when performed in referral centers for robotic surgery, not dedicated to HPB. Our study aimed to verify the efficacy and safety of perioperative outcomes after RLR and OLR for CRLM in an HUB&Spoke learning program (H&S) between a high volume center for liver surgery and high volume center for robotic surgery. Methods: We analyzed prospective databases of Pineta Grande Hospital (Castel Volturno) and Robotic Surgical Units (Foligno-Spoleto and Arezzo) from 2011 to 2021. A 1:1 propensity score matching (PSM) was performed according to baseline characteristics of patients, solitary/multiple CRLM, anterolateral/posterosuperior location. Results: 383 patients accepted to be part of the study (268 ORL and 115 RLR). After PSM, 45 patients from each group were included. Conversion rate was 8.89 %. RLR group had a significantly lower blood loss (226 vs. 321 ml; p=0.0001), and fewer major complications (13.33 % vs. 17.78 %; p=0.7722). R0 resection was obtained in 100% of OLR (vs.95.55%, p =0.4944. Hospital stay was 8.8 days in RLR (vs. 15; p=0.0001).Conclusion: H&S represents a safe and effective program to train general surgeons also in Hepatobiliary surgery providing R0 resection rate, blood loss volume and morbidity rate superimposable to referral centers. Furthermore, H&S allow a reduction of health mobility with consequent money saving for patients and institutions.

Pancreatic Ductal Adenocarcinoma: Update of CT-Based Radiomics Applications in the Pre-Surgical Prediction of the Risk of Post-Operative Fistula, Resectability Status and Prognosis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related deaths worldwide. Surgical resection is the main driver to improving survival in resectable tumors, while neoadjuvant treatment based on chemotherapy (and radiotherapy) is the best option-treatment for a non-primally resectable disease. CT-based imaging has a central role in detecting, staging, and managing PDAC. As several authors have proposed radiomics for risk stratification in patients undergoing surgery for PADC, in this narrative review, we have explored the actual fields of interest of radiomics tools in PDAC built on pre-surgical imaging and clinical variables, to obtain more objective and reliable predictors. METHODS: The PubMed database was searched for papers published in the English language no earlier than January 2018. RESULTS: We found 301 studies, and 11 satisfied our research criteria. Of those included, four were on resectability status prediction, three on preoperative pancreatic fistula (POPF) prediction, and four on survival prediction. Most of the studies were retrospective. CONCLUSIONS: It is possible to conclude that many performing models have been developed to get predictive information in pre-surgical evaluation. However, all the studies were retrospective, lacking further external validation in prospective and multicentric cohorts. Furthermore, the radiomics models and the expression of results should be standardized and automatized to be applicable in clinical practice.

Artificial Intelligence to Early Predict Liver Metastases in Patients with Colorectal Cancer: Current Status and Future Prospectives.

BACKGROUND: Artificial Intelligence (AI)-based analysis represents an evolving medical field. In the last few decades, several studies have reported the diagnostic efficiency of AI applied to Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) to early detect liver metastases (LM), mainly from colorectal cancer. Despite the increase in information and the development of different procedures in several radiological fields, an accurate method of predicting LM has not yet been found. This review aims to compare the diagnostic efficiency of different AI methods in the literature according to accuracy, sensibility, precision, and recall to identify early LM. METHODS: A narrative review of the literature was conducted on PubMed. A total of 336 studies were screened. RESULTS: We selected 17 studies from 2012 to 2022. In total, 14,475 patients were included, and more than 95% were affected by colorectal cancer. The most frequently used imaging tool to early detect LM was found to be CT (58%), while MRI was used in three cases. Four different AI analyses were used: deep learning, radiomics, machine learning, and fuzzy systems in seven (41.18%), five (29.41%), four (23.53%), and one (5.88%) cases, respectively. Four studies achieved an accuracy of more than 90% after MRI and CT scan acquisition, while just two reported a recall rate ≥90% (one method using MRI and CT and one CT). CONCLUSIONS: Routinely acquired radiological images could be used for AI-based analysis to early detect LM. Simultaneous use of radiomics and machine learning analysis applied to MRI or CT images should be an effective method considering the better results achieved in the clinical scenario.

Ventilatory efficiency in post-COVID-19 athletes.

Limitation in exercise capacity has not been described in athletes affected by SARS-CoV-2 infection. However, patients who have recovered from COVID-19 without cardiopulmonary impairment show exaggerated ventilatory response during exercise. Therefore, we aimed to evaluate the ventilatory efficiency (VEf) in competitive athletes recovered from COVID-19 and to characterize the ventilation versus carbon dioxide relationship (VE/VCO2 ) slope in this population. Thirty-seven competitive athletes with COVID-19 were recruited for this study. All participants underwent spirometry, echocardiography, and cardiopulmonary exercise testing (CPET). z-FVC values and end-title pressure of CO2 (PET CO2 ) were lower in the third tertile compared with the first tertile: -0.753 ± 0.473 vs. 0.037 ± 0.911, p = 0.05; 42.2 ± 2.7 vs. 37.1 ± 2.5 mmHg, p < 0.01. VE/VCO2 slope was significantly correlated to maximal VCO2 /VE and maximal VO2 /VE: coefficient = -0.5 R2 = 0.58, p < 0.0001 and coefficient = -0.3 R2 = 0.16, p = 0.008. Competitive athletes affected by SARS-CoV-2 infection, without cardio-respiratory disease sequel, may present ventilatory inefficiency (ViE), without exercise capacity limitation. FVC is higher in athletes with better ventilatory performance during exercise, and increased VE/VCO2 slope is inversely correlated to max VCO2 /VE and max VO2 /VE.

The role of body composition on cardio-respiratory fitness in futsal competitive athletes.

Futsal is an intermittent high intensity sport which has become popular worldwide. Body composition and physical fitness have been studied in different sports disciplines. However, little is known regarding body composition and cardio-respiratory performance in competitive futsal players. Body composition parameters were analyzed by electrical impedance body composition analyzer in 31 competitive male futsal players. All participants performed spirometry, handgrip strength and cardiopulmonary exercise testing. Significant correlations were observed between muscle mass and spirometry parameters and peak VO2 (p≤0.05). Fat mass resulted inversely correlated with peak VO2% predicted and hand grip strength (p≤0.05). Regression analysis showed that muscle mass significantly predicts respiratory parameters (p<0.01) and reduced fat mass is associated with increased peak VO2 % predicted and handgrip strength (p<0.01). In futsal competitive athletes increased muscle mass is associated with higher spirometry parameters and fat mass is inversely associated with lower cardiorespiratory fitness.

Functional and Clinical Importance of SGLT2-inhibitors in Frailty: From the Kidney to the Heart.

SGLT2 (sodium-glucose cotransporter 2) enables glucose and sodium reabsorption in the kidney. SGLT2-inhibitors (also known as gliflozins, which include canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) act by increasing glycosuria, thereby reducing glycemia. These drugs are critical to reach and keep glycemic control, a crucial feature, especially in patients with comorbidities, like frail individuals. Several studies evaluated the effects of SGLT2-inhibitors in different settings beyond diabetes, revealing that they are actually pleiotropic drugs. We recently evidenced the favorable effects of SGLT2-inhibition on physical and cognitive impairment in frail older adults with diabetes and hypertension. In the present overview, we summarize the latest clinical and preclinical studies exploring the main effects of SGLT2-inhibitors on kidney and heart, emphasizing their potential beneficial actions in frailty.

Self-reported side effects following COVID-19 vaccination in athletes: A retrospective study.

Billions of coronavirus disease 19 (COVID-19) vaccines have been administered worldwide. However, limited data on side effects have been reported in athletes. This study aimed to describe the incidence of side effects following COVID-19 vaccination in athletes and to identify the factors associated with the main side effects in this population. Information on COVID-19 vaccination, side effects, and overall symptom duration was retrospectively collected from recreational and competitive athletes. A total of 460 participants were included in this study. Fever and arm pain were more frequently reported after the first-dose vaccination, 9.6% vs 4.6%, p = .007 and 81.3% vs 24.9%, p ≤ .001. Myalgia was more common after the second-dose vaccination, 0.65% vs. 7.1% p ≤ .001. Males were more likely to present with arm pain after the first and second vaccinations. Those with SARS-CoV-2 infection before vaccination were less likely to present with arm pain after the first dose of vaccination (OR: 0.162, p ≤ .001) and more likely to present with fever after the second dose of vaccination (OR: 3.442, p = .046). First-dose vaccination with the BNT162b2 vaccine compared to other brands was characterized by lower odds of fever (OR: 0.394, p = .017). Our results indicated mild adverse effects and a short duration of symptoms in athletes following COVID-19 vaccination.