Human Aging and Age-Related Diseases: From Underlying Mechanisms to Pro-Longevity Interventions.

As human life expectancy continues to rise, becoming a pressing global concern, it brings into focus the underlying mechanisms of aging. The increasing lifespan has led to a growing elderly population grappling with age-related diseases (ARDs), which strains healthcare systems and economies worldwide. While human senescence was once regarded as an immutable and inexorable phenomenon, impervious to interventions, the emerging field of geroscience now offers innovative approaches to aging, holding the promise of extending the period of healthspan in humans. Understanding the intricate links between aging and pathologies is essential in addressing the challenges presented by aging populations. A substantial body of evidence indicates shared mechanisms and pathways contributing to the development and progression of various ARDs. Consequently, novel interventions targeting the intrinsic mechanisms of aging have the potential to delay the onset of diverse pathological conditions, thereby extending healthspan. In this narrative review, we discuss the most promising methods and interventions aimed at modulating aging, which harbor the potential to mitigate ARDs in the future. We also outline the complexity of senescence and review recent empirical evidence to identify rational strategies for promoting healthy aging.

Esophageal cancer: current status and new insights from inflammatory markers - a brief review.

Esophageal cancer (EC) poses a significant challenge to the healthcare system due to its profound impact on cancer-related morbidity and mortality worldwide. This malignancy ranks among the most arduous conditions confronting the surgeon. EC arises from a complex interplay of genetic predispositions and environmental factors. While the incidence of esophageal adenocarcinoma (EAC) is on the rise in the West, esophageal squamous cell carcinoma (ESCC) remains prevalent in the East. Chronic inflammation plays a pivotal role in the initiation and progression of EC. Accordingly, serum inflammatory markers, growth factors, and cytokines have been shown to be clinically useful. Thus, evaluating serum cytokine levels for EC prediction is a safe and feasible screening method. Given the aggressive nature and poor prognosis of the disease, innovative approaches to diagnosis, prognosis, and management of EC are indispensable. This review discusses the major risk factors and the current landscape of EC, with a specific focus on the potential contributions of new inflammatory markers to enhance disease management and improve patient outcomes.

Local intramuscular administration of ANG1 and VEGF genes using plasmid vectors mobilizes CD34+ cells to peripheral tissues and promotes angiogenesis in an animal model.

INTRODUCTION: Patients with peripheral artery disease have poor prognosis despite advances in vascular surgery. Therefore, attempts have been made at using gene and cell therapy to stimulate angiogenesis in the lower limbs in patients with critical lower limb ischemia (CLI). METHODS: The study included 30 rats divided into 3 groups. An intramuscular injection of a therapeutic gene or cells in the right hind limb was administered in each group: angiopoietin-1 (ANG1) plasmid in group 1, ANG1/vascular endothelial growth factor (ANG1/VEGF) bicistronic construct in group 2, and naked plasmid in group 3 (control). After 3 months of follow-up, tissue samples were harvested, and vessels that stained positively for CD34 cells were quantified. RESULTS: The highest CD34+ cell count was noted in the ANG1/VEGF group (98.26 cells), followed by the ANG1 group (80.31) and control group (47.93). The CD34+ cell count was significantly higher in the ANG1/VEGF and ANG1 groups than in the control group. There was no significant difference in the CD34+ cell count between the ANG1/VEGF and ANG1 groups. CONCLUSION: Our study confirmed that therapy with ANG1 plasmid alone or ANG1/VEGF bicistronic construct is safe and effective in a rat model. The therapy resulted in the recruitment of more CD34+ vascular endothelial cells than in the control group receiving naked plasmid.

The Impact of the COVID-19 Emergency on Life Activities and Delivery of Healthcare Services in the Elderly Population.

Due to the prevailing pandemic of the coronavirus disease COVID-19, we are experiencing emotional and social isolation, which negatively affects mental and physical health, particularly among the elderly population. In this study, we performed a cross-sectional analysis based on computer-assisted telephone interviews of 500 Polish adults aged 60 years or older in order to determine the impact of the SARS-CoV-2 pandemic on the older population's behavior, life activity, and delivery of healthcare services. According to our study, COVID-19 infection entailed a substantial change in older people's behavior. Over 50%, nearly 80%, and more than 25% of the surveyed participants reduced their social, recreational, and professional activities, respectively. The most significant change in senior's behavior due to the fear of COVID-19 infection was observed in patients (1) with cardiac and pulmonary problems, (2) being on multi-drug therapy, (3) vaccinated against influenza, and (4) with several mental difficulties including loneliness, social isolation, and depression. Furthermore, we demonstrated that 10% of participants canceled planned hospitalization due to the fear of COVID-19 infection. This was observed primarily in patients suffering from chronic heart and lung diseases, vaccinated against influenza, exhibiting the reluctance to carry out more complex daily activities, and with a higher level of anxiety, social loneliness, and malnutrition. Thus, these groups of seniors require more attention; hence, we propose telemedicine as a strategy directed to them that provides clinical healthcare and information regarding measurements, control, and protection against SARS-CoV-2 during the prevailing COVID-19 pandemic. We believe this strategy may improve treatment outcomes, reduce comorbidities-related complications and unnecessary hospitalizations.

Clinical Characteristics, Preventive Care and Attitude to Telemedicine among Patients with Diabetic Retinopathy: A Cross-Sectional Study.

Diabetic retinopathy (DR) is the most frequent and one of the most severe complications of both types of diabetes. Despite the development of versatile diabetes management programs in most developed countries, many patients remain at increased risk for developing this life-limiting and life-threatening condition. This cross-sectional analysis objective was to examine and compare the prevalence of diabetic retinopathy and comorbidities, as well as the clinical characteristics, prevention patterns, and attitude to telemedicine in patients with diabetes. We found that, when compared to the non-DR group, patients with DR significantly more often utilize clinical preventive services and counseling; however, there is still a significant gap in the receipt of preventative care. Moreover, in the DR subgroup, inadequate diabetic control and the presence of various signs and symptoms of diseases were observed. Although less than a fifth of all patients use mobile applications to monitor their health status, the patients indicate their willingness to use telemedical technology, particularly if it is recommended by the physician and provided without additional costs. The evolution of telemedicine offers a possibility of inexpensive, continuous monitoring of the disease that could improve treatment outcomes. Our observations emphasize DR's perception as a complex disease in which education and continuous monitoring, particularly with telemedicine methods, are critical for further improvement in chronic care.

Double VEGF/HGF Gene Therapy in Critical Limb Ischemia Complicated by Diabetes Mellitus.

Critical leg ischemia (CLI) complicated by diabetes mellitus (DM), which is a very common and dangerous disease, represents the ultimate stage of peripheral arterial disease. Patients are treated with antiplatelet drugs, statins and limb revascularization, but a significant number of patients are not candidate for revascularization. Literature shows that in such cases, gene therapy could be a perfect therapeutic option. The aim of our study was to evaluate efficacy of double vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) gene therapy in patients with CLI complicated by DM. We observed that 90 days after administration, serum level of VEGF and ankle-brachial index increased significantly (p < 0.001) and rest pain decreased significantly compared with the control group (p < 0.002). Moreover considerable improvement in vascularization was observed in computed tomography angiography (P = 0.04). Based on the results of this study, we suggest that the therapy with pIRES/VEGF165/HGF bicistronic plasmid administration is a safe and effective method of treatment of patients with both CLI and DM. Graphical abstract.

A rare case of acute pancreatitis: a diagnostic conundrum and unusual complications.

A 63-year-old man with a history of recurrent idiopathic acute pancreatitis (AP) was admitted to our surgical ward due to severe abdominal pain. He denied chronic excessive alcohol use. Other typical causes of AP, such as gallstones, hypertriglyceridemia, and trauma, were ruled out. After considering all possible etiologies, the most likely factor producing AP was medication that had been administered to him two weeks before the very first episode of the disease. Medication should always be considered as a possible trigger of AP, especially if the first episode occurs shortly after drug administration and the etiology is unclear. During patient's hospitalization, laboratory reports revealed significant fluctuations in the serum levels of pancreatic enzymes, which can be attributed to recurrent bacteremia. After the 30-day period of hospitalization and long-lasting antibiotic therapy, he was discharged in a good condition with normal levels of serum pancreatic enzymes.

A rare case of acute pancreatitis: a diagnostic conundrum and unusual complications.

A 63-year-old man with a history of recurrent idiopathic acute pancreatitis (AP) was admitted to our surgical ward due to severe abdominal pain. He denied chronic excessive alcohol use. Other typical causes of AP, such as gallstones, hypertriglyceridemia, and trauma, were ruled out. After considering all possible etiologies, the most likely factor producing AP was medication that had been administered to him two weeks before the very first episode of the disease. Medication should always be considered as a possible trigger of AP, especially if the first episode occurs shortly after drug administration and the etiology is unclear. During patient's hospitalization, laboratory reports revealed significant fluctuations in the serum levels of pancreatic enzymes, which can be attributed to recurrent bacteremia. After the 30-day period of hospitalization and long-lasting antibiotic therapy, he was discharged in a good condition with normal levels of serum pancreatic enzymes.

Zenker diverticulum: Experience in surgical treatment of large diverticula.

The purpose of this retrospective study is to show that transcervical diverticulectomy (TD) in treatment of Zenker diverticulum (ZD) can still be a first choice procedure in selected patients and in experienced hands its safety might be compared to the minimally invasive endoscopic diverticulostomy.The study cohort consisted of 44 patients (18 male, 26 female) operated for (ZD). All the patients underwent open diverticulectomy. The decision to choose open surgical repair depended on surgical risk, age of the patient, size of the diverticular septum (the distance between the top of the diverticulum and its bottom on barium study), and patient's preference.Mean age of patients was 64.6 ±â€Š11.9 years; range: 26 to 88 years. A total of 36.4% out of them finished 70 years. Postoperative mortality was nil. Two major complications (4.5%) requiring surgical intervention occurred: leak and hematoma.Data were analyzed by t test for independent samples using Statistica 12.5 software. P value <0.05 was considered statistically significant.Surgical treatment of patients with ZD should be individualized. Large Zenker diverticula with the septum longer than 6 cm should preferably be resected through an open approach because it is not possible to remove the septum completely during one-step endoscopic procedure and diverticulostomy creates a weak and large common cavity in the esophagus. Surgical repair is effective for all sizes of diverticula, but its most serious complications such as leakage or laryngeal nerve injury should be considered, especially in elderly patients with comorbidities. However, age alone should not be the main criterion if choosing the treatment option.

The association between total leukocyte count and longevity: Evidence from longitudinal and cross-sectional data.

The aim of the study was to evaluate the relationship between age-dependent changes in total leukocyte count (TLC) and certain selected differential counts expressed as frequencies (granulocytes, band cells, eosinophils, lymphocytes, and monocytes) and longevity in physically healthy men and women aged 45+. Longitudinal data on cell counts from 142 subjects (68 men and 74 women; all aged 45-70 and examined for 25 years) were compared with cross-sectional data from 225 subjects (113 men and 112 women; this group was divided into four categories of average lifespan; i.e.: 53, 63, 68, and 76+ years of age). ANOVA, t-test, and regression analysis were employed. Secular changes in leukocyte count were controlled. Men had continuously higher TLC compared with women. Moreover, sex differences in patterns of changes with age were found. The longitudinal assessment revealed a U-shaped pattern of changes in TLC in men (y=0.0026x(2)-0.2866x+14.4374; R(2)=0.852) and women (y=0.0048x(2)-0.5386x+20.922; R(2)=0.938), whereas the cross-sectional comparison showed an inverted U-shaped pattern in men (y=-0.0021x(2)+0.2421x; R(2)=0.417) and women (y=-0.0017x(2)+0.2061x; R(2)=0.888). In general, the comparison of longitudinal and cross-sectional data on changes with age in TLC indicates that longevity favors individuals with lower yet normal TLC and this correlation is more pronounced in men. In conclusion, our findings are in line with previous longitudinal studies of aging and suggest that lower TLC within the normal range (4.0-10.0 × 10(3)µL(-1)) can be a useful predictor of longevity in physically healthy individuals.