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.

Endothelial microRNAs in INOCA patients with diabetes mellitus.

Ischemia with non-obstructive coronary artery (INOCA) is a common cause of hospital admissions, leading to negative outcomes and reduced quality of life. Central to its pathophysiology is endothelial dysfunction, which contributes to myocardial ischemia despite the absence of significant coronary artery blockage. Addressing endothelial dysfunction is essential in managing INOCA to alleviate symptoms and prevent cardiovascular events. Recent studies have identified diabetes mellitus (DM) as a significant factor exacerbating INOCA complications by promoting endothelial impairment and coronary microvascular dysfunction. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets in various biological processes, including endothelial dysfunction and cardiovascular diseases. However, research on miRNA biomarkers in INOCA patients is sparse. In this study, we examined a panel of circulating miRNAs involved in the regulation of endothelial function in INOCA patients with and without DM. We analyzed miRNA expression using RT-qPCR in a cohort of consecutive INOCA patients undergoing percutaneous coronary intervention. We detected a significant dysregulation of miR-363-5p and miR-92a-3p in INOCA patients with DM compared to those without DM, indicating their role as biomarkers for predicting and monitoring endothelial dysfunction in INOCA patients with DM.

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.

Frailty and Parkinson's disease: the role of diabetes mellitus.

Parkinson's disease (PD) is a chronic neurodegenerative disease associated with a progressive loss of dopaminergic neurons, clinically characterized by motor and non-motor signs. Frailty is a clinical condition of increased vulnerability and negative health outcomes due to the loss of multiple physiological reserves. Chronic hyperglycemia and insulin resistance, which characterize diabetes mellitus (DM), have been reported to alter dopaminergic activity, increase the risk of PD, and influence the development of frailty. Even though diabetes may facilitate the development of frailty in patients with PD, this relationship is not established and a revision of the current knowledge is necessary. Furthermore, the synergy between DM, PD, and frailty may drive clinical complexity, worse outcomes, and under-representation of these populations in the research. In this review, we aimed to discuss the role of diabetes in the development of frailty among patients with PD. We summarized the clinical characteristics and outcomes of patients with concomitant DM, PD, and frailty. Finally, interventions to prevent frailty in this population are discussed.

Time to negative conversion and cardiopulmonary performance in athletes with COVID-19.

Athletes with longer time to negative conversion for COVID-19 do not present reduction of exercise capacity. However, respiratory and ventilatory parameters are modified. https://bit.ly/3TMdrFL.

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.

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.

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.

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.

Emergency robotic surgery: the experience of a single center and review of the literature.

BACKGROUNDS: Laparoscopic surgery is widely used in abdominal emergency surgery (AES), and the possibility of extending this approach to the more recent robotic surgery (RS) arouses great interest. The slow diffusion of robotic technology mainly due to high costs and the longer RS operative time when compared to laparoscopy may represent disincentives, especially in AES. This study aims to report our experience in the use of RS in AES assessing its safety and feasibility, with particular focus on intra- and post-operative complications, conversion rate, and surgical learning curve. Our data were also compared to other experiences though an extensive literature review. METHODS: We retrospectively analysed a single surgeon series of the last 10 years. From January 2014 to December 2023, 36 patients underwent urgent or emergency RS. The robotic devices used were Da Vinci Si (15 cases) and Xi (21 cases). RESULTS: 36 (4.3%) out of 834 robotic procedures were included in our analysis: 20 (56.56%) females. The mean age was 63 years and 30% of patients were ≥ 70 years. 2 (5.55%) procedures were performed at night. No conversions to open were reported in this series. According to the Clavien-Dindo classification, 2 (5.5%) major complications were collected. Intraoperative and 30-day mortality were 0%. CONCLUSIONS: Our study demonstrates that RS may be a useful and reliable approach also to AES and intraoperative laparoscopic complications when performed in selected hemodynamically stable patients in very well-trained robotic centers. The technology may increase the minimally invasive use and conversion rate in emergent settings in a completely robotic or hybrid approach.

Endotyping Chronic Respiratory Diseases: T2 Inflammation in the United Airways Model.

Over the past 15 years, the paradigm of viewing the upper and lower airways as a unified system has progressively shifted the approach to chronic respiratory diseases (CRDs). As the global prevalence of CRDs continues to increase, it becomes evident that acknowledging the presence of airway pathology as an integrated entity could profoundly impact healthcare resource allocation and guide the implementation of pharmacological and rehabilitation strategies. In the era of precision medicine, endotyping has emerged as another novel approach to CRDs, whereby pathologies are categorized into distinct subtypes based on specific molecular mechanisms. This has contributed to the growing acknowledgment of a group of conditions that, in both the upper and lower airways, share a common type 2 (T2) inflammatory signature. These diverse pathologies, ranging from allergic rhinitis to severe asthma, frequently coexist and share diagnostic and prognostic biomarkers, as well as therapeutic strategies targeting common molecular pathways. Thus, T2 inflammation may serve as a unifying endotypic trait for the upper and lower airways, reinforcing the practical significance of the united airways model. This review aims to summarize the literature on the role of T2 inflammation in major CRDs, emphasizing the value of common biomarkers and integrated treatment strategies targeting shared molecular mechanisms.

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.

Prediabetes Increases the Risk of Frailty in Prefrail Older Adults With 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.