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.

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.

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.

Imaging of Ganglioneuroma: A Literature Review and a Rare Case of Cystic Presentation in an Adolescent Girl.

Retroperitoneal ganglioneuroma is a rare neuroectodermal tumor with a benign nature. We performed a literature review among 338 studies. We included 9 studies, whose patients underwent CT and/or MRI to characterize a retroperitoneal mass, which was confirmed to be a ganglioneuroma by histologic exam. The most common features of ganglioneuroma are considered to be a solid nature, oval/lobulated shape, and regular margins. The ganglioneuroma shows a progressive late enhancement on CT. On MRI it appears as a hypointense mass in T1W images and with a heterogeneous high-intensity in T2W. The MRI-"whorled sign" is described in the reviewed studies in about 80% of patients. The MRI characterization of a primitive retroperitoneal cystic mass should not exclude a cystic evolution from solid masses, and in the case of paravertebral location, the differential diagnosis algorithm should include the hypothesis of ganglioneuroma. In our case, the MRI features could have oriented towards a neurogenic nature, however, the predominantly cystic-fluid aspect and the considerable longitudinal non-invasive extension between retroperitoneal structures, misled us to a lymphatic malformation. In the literature, it is reported that the cystic presentation can be due to a degeneration of a well-known solid form while maintaining a benign character: the distinguishing malignity character is the revelation of immature cells on histological examination.

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.

Sialylation status in placentas from pregnancies with SARS-CoV-2 infection.

INTRODUCTION: Recent investigations suggest the potential negative impact of SARS-CoV-2 infection on pregnant women and pregnancy outcome. In addition, some studies have described pathological changes in the placental tissue of SARS-CoV-2-positive mothers, which are related or not to the infection severity and/or infection trimester. Among the various molecules involved in the normal structure and functionality of the placenta, sialic acids (Sias) seem to play an important role. Hence, we aimed to investigate possible changes in the distribution and content of Sias with different glycosidic linkages, namely α2,3 and α2,6 Galactose- or N-acetyl-Galactosamine-linked Sias and polymeric Sia (PolySia), in placentas from pregnant women infected by SARS-CoV-2 during the three different pregnancy trimesters. METHODS: α2,3 and α2,6 Galactose-linked Sias were evaluated by lectin histochemistry (Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA), respectively), while immunohistochemistry was used for PolySia detection. RESULTS: Data showed lower levels of α2,3 Galactose-linked Sias in the trophoblast and underlying basement membrane/basal plasma membrane in placentas from women infected during the second and third infection trimester compared with uninfected cases and those infected during first trimester. On the other hand, higher levels of PolySia were detected in the trophoblast during the second and third infection trimester. CONCLUSIONS: Our findings suggest that changes in the sialylation status of trophoblast and its basement membrane/basal plasma membrane, together with other concomitant factors, could be at the basis of the most common placental histopathological alterations and gestational complications found especially in pregnancies with SARS-CoV-2 infection during the second and third trimester.

Antiinflammatory Activities of Curcumin and Spirulina: Focus on Their Role against COVID-19.

Nutraceuticals have for several years aroused the interest of researchers for their countless properties, including the management of viral infections. In the context of the COVID-19 pandemic, studies and research on the antiviral properties of nutraceuticals have greatly increased. More specifically, over the past two years, researchers have focused on analyzing the possible role of nutraceuticals in reducing the risk of SARS-CoV-2 infection or mitigating the symptoms of COVID-19. Among nutraceuticals, turmeric, extracted from the rhizome of the Curcuma Longa plant, and spirulina, commercial name of the cyanobacterium Arthrospira platensis, have assumed considerable importance in recent years. The purpose of this review is to collect, through a search of the most recent articles on Pubmed, the scientific evidence on the role of these two compounds in the fight against COVID-19. In the last two years many hypotheses, some confirmed by clinical and experimental studies, have been made on the possible use of turmeric against COVID-19, while on spirulina and its possible role against SARS-CoV-2 infection information is much less. The demonstrated antiviral properties of spirulina and the fact that these cyanobacteria may modulate or modify some mechanisms also involved in the onset of COVID-19, lead us to think that it may have the same importance as curcumin in fighting this disease and to speculate on the possible combined use of these two substances to obtain a synergistic effect.

The Molecular Heterogeneity of Store-Operated Ca2+ Entry in Vascular Endothelial Cells: The Different roles of Orai1 and TRPC1/TRPC4 Channels in the Transition from Ca2+-Selective to Non-Selective Cation Currents.

Store-operated Ca2+ entry (SOCE) is activated in response to the inositol-1,4,5-trisphosphate (InsP3)-dependent depletion of the endoplasmic reticulum (ER) Ca2+ store and represents a ubiquitous mode of Ca2+ influx. In vascular endothelial cells, SOCE regulates a plethora of functions that maintain cardiovascular homeostasis, such as angiogenesis, vascular tone, vascular permeability, platelet aggregation, and monocyte adhesion. The molecular mechanisms responsible for SOCE activation in vascular endothelial cells have engendered a long-lasting controversy. Traditionally, it has been assumed that the endothelial SOCE is mediated by two distinct ion channel signalplexes, i.e., STIM1/Orai1 and STIM1/Transient Receptor Potential Canonical 1(TRPC1)/TRPC4. However, recent evidence has shown that Orai1 can assemble with TRPC1 and TRPC4 to form a non-selective cation channel with intermediate electrophysiological features. Herein, we aim at bringing order to the distinct mechanisms that mediate endothelial SOCE in the vascular tree from multiple species (e.g., human, mouse, rat, and bovine). We propose that three distinct currents can mediate SOCE in vascular endothelial cells: (1) the Ca2+-selective Ca2+-release activated Ca2+ current (ICRAC), which is mediated by STIM1 and Orai1; (2) the store-operated non-selective current (ISOC), which is mediated by STIM1, TRPC1, and TRPC4; and (3) the moderately Ca2+-selective, ICRAC-like current, which is mediated by STIM1, TRPC1, TRPC4, and Orai1.

SARS-CoV-2 Infection: A Clinical and Histopathological Study in Pregnancy.

During pregnancy, SARS-CoV-2 infection is associated with several adverse outcomes, including an increased risk of pre-eclampsia, preterm delivery, hypertensive disorders, gestational diabetes, and fetal growth restriction related to the development of placenta vascular abnormalities. We analyzed human placenta from full-term, uncomplicated pregnancies with SARS-CoV-2 infection during the first, second, or third trimesters of gestation. We studied, by the immunohistochemistry technique, the expression of CD34 and podoplanin (PDPN) as markers of vasculogenesis to find any differences. As secondary outcomes, we correlated maternal symptoms with placental histological alterations, including fibrin deposits, lymphocyte infiltration in the villi, edema, and thrombi. Our results showed a PDPN expression around the villous stroma as a plexiform network around the villous nucleus of fetal vessels; significant down-regulation was observed in the villous stroma of women infected during the third trimester. CD34 showed no changes in expression levels. During SARS-CoV-2 infection, the most common maternal symptoms were fever, anosmia, ageusia and asthenia, and the majority were treated with paracetamol, corticosteroids and azithromycin. Patients that required multiple symptomatic treatments evidenced a large amount of fibrin deposition in the villi. Certainly, PDPN plays a key role in healthy placental vasculogenesis and thus in its proper physiology, and SARS-CoV-2 surely alters its normal expression. Further studies are necessary to understand what mechanisms are being altered to try to avoid possible complications for both the mother and fetus in terms of the contagions that will still occur.

Role of Endothelial Progenitor Cells in Frailty.

Frailty is a clinical condition closely related to aging which is characterized by a multidimensional decline in biological reserves, a failure of physiological mechanisms and vulnerability to minor stressors. Chronic inflammation, the impairment of endothelial function, age-related endocrine system modifications and immunosenescence are important mechanisms in the pathophysiology of frailty. Endothelial progenitor cells (EPCs) are considered important contributors of the endothelium homeostasis and turn-over. In the elderly, EPCs are impaired in terms of function, number and survival. In addition, the modification of EPCs' level and function has been widely demonstrated in atherosclerosis, hypertension and diabetes mellitus, which are the most common age-related diseases. The purpose of this review is to illustrate the role of EPCs in frailty. Initially, we describe the endothelial dysfunction in frailty, the response of EPCs to the endothelial dysfunction associated with frailty and, finally, interventions which may restore the EPCs expression and function in frail people.