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 challenges and perspectives in lung cancer care during COVID-19 waves.

PURPOSE OF REVIEW: In the era of the SARS-Cov2 pandemic, the multidisciplinary care of patients with lung cancer is the main challenge for clinicians. The depiction of complex networking between SARS-CoV2 and cancer cells is crucial to understanding the downstream signalling pathways leading to more severe clinical behaviour of COVID-19 among lung cancer patients. RECENT FINDINGS: The immunosuppressive status caused by both blunted immune response and active anticancer treatments (e.g. radiotherapy, chemotherapy) affects also the response to vaccines. Furthermore, the COVID-19 pandemic has significantly influenced early detection, therapeutic management, and clinical research for patients with lung cancer. SUMMARY: SARS-CoV-2 infection does undoubtedly represent a challenge for care of patients with lung cancer. Since symptoms of infection may overlap with underlying condition, diagnosis must be reached and treatment should start as soon as possible. Although any cancer treatment should be procrastinated as long as infection is not cured, every choice must be pondered on individual basis, according to clinical conditions. Underdiagnosis should be avoided, and both surgical and medical treatment must be tailored to each patient. Therapeutic scenario standardization represents a major challenge for clinicians and researchers.

Transient Receptor Potential (TRP) Channels in Tumor Vascularization.

Tumor diseases are unfortunately quick spreading, even though numerous studies are under way to improve early diagnosis and targeted treatments that take into account both the different characteristics associated with the various tumor types and the conditions of individual patients. In recent years, studies have focused on the role of ion channels in tumor development, as these proteins are involved in several cellular processes relevant to neoplastic transformation. Among all ion channels, many studies have focused on the superfamily of Transient Receptor Potential (TRP) channels, which are non-selective cation channels mediating extracellular Ca2+ influx. In this review, we examined the role of different endothelial TRP channel isoforms in tumor vessel formation, a process that is essential in tumor growth and metastasis.

Delirium in Nursing Home Residents: A Narrative Review.

Delirium is an important component of the geriatric syndromes and has been recognized to negatively influence the prognosis of older people in hospital and in a post-acute setting. About 2-5% of older people world-wide live in nursing homes and are characterized by functional impairment, cognitive decline, dementia, comorbidities, and polypharmacotherapy, all factors which influence the development of delirium. However, in this setting, delirium remains often understudied. Therefore, in this narrative review, we aimed to describe the latest evidence regarding delirium screening tools, epidemiology characteristics, outcomes, risk factors, and preventions strategies in nursing homes.

Frailty in Patients With Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous studies regarding the prevalence of frailty in patients with lung cancer and mortality in frail patients with lung cancer are inconsistent and require clarification. RESEARCH QUESTION: What is the prevalence and impact of frailty in patients with lung cancer? STUDY DESIGN AND METHODS: This systematic review and meta-analysis used a combination of free-text terms and medical subject headings terms, according to the database requirements in MEDLINE/PubMed, Scopus, and Cochrane Library from inception until November 15, 2020. RESULTS: A total of 2,571 articles were identified, and 16 articles involving 4,183 patients were included for study. The prevalence of frailty in lung cancer was 45% (95% CI, 28-61; I2 = 99.5%; P < .0001). In patients with lung cancer, frailty was associated with an increased hazard ratio for mortality (hazard ratio, 3.01; 95% CI, 1.77-5.10; P < .001). INTERPRETATION: The prevalence of frailty in lung cancer is 45%, which has a significant negative impact on survival of patients with lung cancer. These results highlight the importance of measuring frailty, which provides important prognostic information, and may provide opportunities for interventions to improve outcomes in patients with lung cancer.

The Prevalence and the Impact of Frailty in Hepato-Biliary Pancreatic Cancers: A Systematic Review and Meta-Analysis.

BACKGROUND: Frailty has been associated with increased mortality among hepatobiliary pancreatic (HBP) cancer patients. Nevertheless, estimates of frailty prevalence in HBP cancers and the precise average effect regarding mortality remains uncertain. The present systematic review and meta-analysis aimed to quantify: (1) the prevalence of frailty in patients with liver and pancreatic cancers and (2) the impact of frailty on mortality in patients affected by liver and pancreatic cancers. METHODS: MEDLINE/PubMed database search was conducted from inception until 1 November 2021, the pooled prevalence and relative risk (RR) estimate were calculated. RESULTS: A total of 34,276 patients were identified and the weighted prevalence of frailty was 39%; (95% [C.I.] 23-56; I2 = 99.9%, p < 0.0001). Frailty was significantly associated with increased mortality RR 1.98 (95% [C.I.] 1.49-2.63; I2 = 75.9%, p = 0.006). CONCLUSIONS: Frailty prevalence is common among HBP cancer patients and exerts a significant negative impact on survival. These findings are characterized by significant heterogeneity and caution is warranted on their interpretation. However, stratification of patients with HBP cancer by frailty status may provide prognostic information and may inform priorities for decision-making strategy.

Evolving concepts in COPD and lung cancer: a narrative review.

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) represent leading causes of morbidity and mortality worldwide. Common risk factors lead to an increased inflammatory response, enhances oxidative stress, and changes in lung microenvironment contributing to fine-tuned interaction between these respiratory disorders. Despite evidence that COPD represents a main risk factor for LC, assessment of LC risk features among COPD patients is not routinely considered in the clinical practice. In LC patients concurrent COPD may impact on clinical scenario influencing the response to treatment. Better understanding LC and COPD coexistence may impact on clinical scenario influencing therapeutic approach. In this review, we describe the basis of this network and how the complex interplay between these respiratory disorders affects the clinical decision-making process.

Minimally Invasive Approach to Gastric GISTs: Analysis of a Multicenter Robotic and Laparoscopic Experience with Literature Review.

Background: Gastrointestinal stromal tumors (GISTs) are most frequently located in the stomach. In the setting of a multidisciplinary approach, surgery represents the best therapeutic option, consisting mainly in a wedge gastric resection. (1) Materials and methods: Between January 2010 to September 2020, 105 patients with a primary gastrointestinal stromal tumor (GISTs) located in the stomach, underwent surgery at three surgical units. (2) Results: A multi-institutional analysis of minimally invasive series including 81 cases (36 laparoscopic and 45 robotic) from 3 referral centers was performed. Males were 35 (43.2%), the average age was 66.64 years old. ASA score ≥3 was 6 (13.3%) in the RS and 4 (11.1%) in the LS and the average tumor size was 4.4 cm. Most of the procedures were wedge resections (N = 76; 93.8%) and the main operative time was 151 min in the RS and 97 min in the LS. Conversion was necessary in five cases (6.2%). (3) Conclusions: Minimal invasive approaches for gastric GISTs performed in selected patients and experienced centers are safe. A robotic approach represents a useful option, especially for GISTs that are more than 5 cm, even located in unfavorable places.

Impact of the number of comorbidities on cardiac sympathetic derangement in patients with reduced ejection fraction heart failure.

INTRODUCTION: Heart failure (HF) is frequently associated with comorbidities. 123I-metaiodobenzylguanidine (123I-mIBG) imaging constitutes an effective tool to measure cardiac adrenergic innervation and to improve prognostic stratification in HF patients, including the risk of major arrhythmic events. Although comorbidities have been individually associated with reduced cardiac adrenergic innervation, thus suggesting increased arrhythmic risk, very comorbid HF patients seem to be less likely to experience fatal arrhythmias. We evaluated the impact of the number of comorbidities on cardiac adrenergic innervation, assessed through 123I-mIBG imaging, in patients with systolic HF. METHODS: Patients with systolic HF underwent clinical examination, transthoracic echocardiography and cardiac 123I-mIBG scintigraphy. The presence of 7 comorbidities/conditions (smoking, chronic obstructive pulmonary disease, diabetes mellitus, peripheral artery disease, atrial fibrillation, chronic ischemic heart disease and chronic kidney disease) was documented in the overall study population. RESULTS: The study population consisted of 269 HF patients with a mean age of 66±11 years, a left ventricular ejection fraction (LVEF) of 31±7%, and 153 (57%) patients presented ≥3 comorbidities. Highly comorbid patients presented a reduced late heart to mediastinum (H/M) ratio, while no significant differences emerged in terms of early H/M ratio and washout rate. Multiple regression analysis revealed that the number of comorbidities was not associated with mIBG parameters of cardiac denervation, which were correlated with age, body mass index and LVEF. CONCLUSION: In systolic HF patients, the number of comorbidities is not associated with alterations in cardiac adrenergic innervation. These results are consistent with the observation that very comorbid HF patients suffer lower risk of sudden cardiac death.

Systemic lupus erythematosus, endothelial progenitor cells and intracellular Ca2+ signaling: A novel approach for an old disease.

Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease featured by an increased cardiovascular risk that may lead to premature patient's death. It has been demonstrated that SLE patients suffer from early onset endothelial dysfunction which is due to the impairment of endogenous vascular repair mechanisms. Vascular integrity and homeostasis are maintained by endothelial progenitor cells (EPCs), which are mobilized in response to endothelial injury to replace damaged endothelial cells. Two main EPCs subpopulations exist in peripheral blood: endothelial colony forming cells (ECFCs), which represent truly endothelial precursors and can physically engraft within neovessels, and myeloid angiogenic cells (MACs), which sustain angiogenesis in a paracrine manner. Emerging evidence indicates that ECFCs/MACs are down-regulated and display compromised angiogenic activity in SLE, thereby contributing to the pathogenesis of this disease. Intracellular calcium (Ca2+) signaling plays a crucial role in maintaining vascular integrity by stimulating migration, proliferation and tube formation in both ECFCs and MACs. Herein, we illustrate the evidences that support the role played by EPCs dysfunction in SLE. Subsequently, we discuss about the hypothesis that the Ca2+ handling machinery is compromised in SLE-derived ECFCs and MACs, thereby resulting in their reduced pro-angiogenic activity. Finally, we speculate about the proposal to exploit intracellular Ca2+ signaling to improve ECFCs' reparative phenotype and suggest this strategy as a new approach to treat SLE patients.

COVID-19 and the elderly: insights into pathogenesis and clinical decision-making.

The elderly may represent a specific cluster of high-risk patients for developing COVID-19 with rapidly progressive clinical deterioration. Indeed, in older individuals, immunosenescence and comorbid disorders are more likely to promote viral-induced cytokine storm resulting in life-threatening respiratory failure and multisystemic involvement. Early diagnosis and individualized therapeutic management should be developed for elderly subjects based on personal medical history and polypharmacotherapy. Our review examines the pathogenesis and clinical implications of ageing in COVID-19 patients; finally, we discuss the evidence and controversies in the management in the long-stay residential care homes and aspects of end-of-life care for elderly patients with COVID-19.

Risk of acute myocardial infarction after transurethral resection of prostate in elderly.

BACKGROUND: Benign prostatic hyperplasia is a frequent disease among elderly, and is responsible for considerable disability. Benign prostatic hyperplasia can be clinically significant due to lower urinary tract symptoms that take place because the gland is enlarged and obstructs urine flow. Transurethral resection of the prostate remains the gold standard treatment for patients with moderate or severe symptoms who need active treatment or who either fail or do not want medical therapy. Moreover, perioperative and postoperative surgery complications as cardiovascular ones still occur. The incidence of acute myocardial infarction in patients undergoing transurethral resection of the prostate is controversial. The first studies showed an increase in mortality and relative risk of death from myocardial infarction in transurethral resection of the prostate group vs open prostatectomy but these results are in contrast with more recent data. DISCUSSION: Given the conflicting evidence of the studies in the literature, in this review we are going to discuss the factors that may influence the risk of myocardial infarction in elderly patients undergoing prostate surgery. We analyzed the possible common factors that lead to the development of myocardial infarction and benign prostatic hyperplasia (cardiovascular and metabolic), the stressor factors related to prostatectomy (surgical and haemodynamic) and the risk factors specific of the elderly population (comorbidity and therapies). SUMMARY: Although transurethral resection of the prostate is considered at low risk for severe complications, there are several reports indicating that cardiovascular events in elderly patients undergoing this surgical operation are more common than in the general population. Several cardio-metabolic, surgical and aging-related factors may help explain this observation but results in literature are not concord, especially due to the fact that most data derive from retrospective studies in which selection bias cannot be excluded. Subsequently, further studies are necessary to clarify the incidence of acute myocardial infarction in old people.

Vascular endothelial growth factor blockade prevents the beneficial effects of ß-blocker therapy on cardiac function, angiogenesis, and remodeling in heart failure.

BACKGROUND: Impaired angiogenesis in the post-myocardial infarction heart contributes to the progression to heart failure. The inhibition of vascular endothelial growth factor (VEGF) signaling has been shown to be crucial for the transition from compensatory hypertrophy to cardiac failure. Importantly, ß-adrenergic receptor blocker therapy has been also shown to improve myocardial perfusion by enhancing neoangiogenesis in the failing heart. METHODS AND RESULTS: Eight weeks from surgically induced myocardial infarction, heart failure rats were randomized to receive bisoprolol (B) or vehicle. At the end of a 10-week treatment period, echocardiography revealed reduced cardiac diameters and improved cardiac function in B-treated compared with vehicle-treated rats. Moreover, B treatment was associated with increased cardiac angiogenesis and in vivo coronary perfusion and reduced cardiac fibrosis. Importantly, 2 weeks after B treatment was started, increased cardiac VEGF expression and Akt and endothelial NO synthase activation were observed by comparing B-treated with drug-untreated failing hearts. To test whether the proangiogenic effects of B act via activation of VEGF pathway, rats were intravenously injected with adenoviral vector encoding a decoy VEGF receptor (Ad-Flk) or a control adenovirus (Ad-C), at the start of the treatment with B. After 10 weeks, histological analysis revealed reduced capillary and coronary perfusion in B-treated plus Ad-Flk rats compared with B-treated plus Ad-C rats. Moreover, VEGF inhibition counteracted the positive effects of B on cardiac function and remodeling. CONCLUSIONS: ß-Blockade promotes cardiac angiogenesis in heart failure via activation of VEGF signaling pathway. ß-Blocker-induced enhancement of cardiac angiogenesis is essential for the favorable effects of this therapy on cardiac function and remodeling.

Oral anticoagulation therapy in heart failure patients in sinus rhythm: a systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) patients show high morbidity and mortality rate with increased risk of malignant arrhythmia and thromboembolism. Anticoagulation reduces embolic event and death rates in HF patients with atrial fibrillation, but if antithrombotic therapy is beneficial in patients with HF in sinus rhythm is still debated. METHODOLOGY AND PRINCIPAL FINDINGS: We conducted a systematic review of prospective, randomized controlled trials (RCTs) to assess the efficacy and safety of oral anticoagulant therapies (OATs) compared to antiplatelet treatment in HF patients in sinus rhythm. MEDLINE, Web of Science, CENTRAL and Scopus databases were searched up to May 2012. Four RCTs were identified and a total of 3663 patients were included in the meta-analysis. Patients with both ischemic and non-ischemic HF were included. There was no significant difference in mortality (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.86 to 1.19) between OATs group and antiplatelet drug group. OATs have reduced ischemic stroke risk (OR 0.49, 95% CI 0.32 to 0.74), but have increased major bleeding risk (OR 2.01, 95% CI 1.40 to 2.88) compared to antiplatelet treatment. CONCLUSION: In HF patients in sinus rhythm OATs do not show a better risk-benefit profile compared to antiplatelet treatment in cardioembolism prevention. Warfarin and aspirin seem to be similar in reducing mortality. Warfarin reduces the incidence of ischemic stroke, but increases major bleedings. Thus, it is possible to speculate that aspirin prescription be indicated in patients with high risk of bleeding, whereas warfarin could be preferred in patients with high thromboembolic risk.