Longitudinal Muscle Biopsies Reveal Inter- and Intra-Subject Variability in Cancer Cachexia: Paving the Way for Biopsy-Guided Tailored Treatment.

In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research.

Adherence to Treatment, Arterial Stiffness and Cognitive Function in Irbesartan- Treated Newly Diagnosed Hypertensive Patients.

OBJECTIVE: Non-adherence to antihypertensive agents leads to reduced blood pressure (BP) control. Data supporting the correlation of adherence with arterial stiffness (AS) are few. Furthermore, the causal relationship between AS and cognitive dysfunction (CO/DY) has not been clearly established. It is suggested that angiotensin II receptor blockers (ARBs) exhibit the lowest discontinuation rate among antihypertensive drugs. DESIGN AND METHODS: We followed up with patients receiving monotherapy with irbesartan. CO/DY was assessed with the Mini-Mental State Examination (MΜSE) and other tests. RESULTS: Patients [n=77; mean age: 56±11 years; 39 men (50.6%)] were followed-up for 16.1±10.9 months. At the end of follow up, significant reductions were observed in mean peripheral systolic BP (135±117 vs 153±11 mmHg; p<0.005), mean peripheral diastolic BP (85±11 vs 95±10 mmHg; p<0.005), mean central systolic BP (130±11 vs 142±12 mmHg; p<0.005) as well as in mean central diastolic BP (85±8 vs 95±97 mmHg; p<0.005). AS indices [carotid-femoral pulse wave velocity and augmentation index] also improved significantly: 7.7±1.4 vs 8.2±1.4 m/sec (p<0.005), and 29.1±8.3 vs 32.3±9.1 (p<0.005), respectively. At the end of the study, a significant improvement was observed in the MMSE test (29.7±0.7 vs. 29.2±0.9; p<0.02), as well as a significant reduction in 24h urine albumin (94±82 vs. 204±112 mg/24h, p<0.005). The level of adherence was high in 60/77 (77.9%), medium in 9/77 (11.6%) and low in 8/77 (10.38%) patients. CONCLUSION: Hypertensive patients receiving mono-therapy with an ARB showed reduced AS, cognitive improvement, significant reductions in BP (peripheral and central) and decreased 24h urinary albumin excretion.

Arterial Stiffness, Cognitive Dysfunction and Adherence to Antihypertensive Agents. Is there a Link to Hypertensive Patients?

The incidence of hypertension (HTN) and its cardiovascular (CV) complications are increasing throughout the world. Blood pressure (BP) control remains unsatisfactory worldwide. Medical inertia and poor adherence to treatment are among the factors that can partially explain, why BP control rate remains low. The introduction of a method for measuring the degree of adherence to a given medication is now a prerequisite. Complex treatment regimes, inadequate tolerance and frequent replacements of pharmaceutical formulations are the most common causes of poor adherence. In contrast, the use of stable combinations of antihypertensive drugs leads to improved patient adherence. We aim to review the relationships between arterial stiffness, cognitive function and adherence to medication in patients with HTN. Large artery stiffening can lead to HTN. In turn, arterial stiffness induced by HTN is associated with an increased CV and stroke risk. In addition, HTN can induce disorders of brain microcirculation resulting in cognitive dysfunction. Interestingly, memory cognitive dysfunction leads to a reduced adherence to drug treatment. Compliance with antihypertensive treatment improves BP control and arterial stiffness indices. Early treatment of arterial stiffness is strongly recommended for enhanced cognitive function and increased adherence.

Arterial damage and cognitive decline in chronic kidney disease patients.

In the general population aortic stiffening, assessed by carotid femoral pulse wave velocity (cf-PWV), is associated with cognitive dysfunction (CO/DY). Data in chronic kidney disease (CKD) are limited. This study tests the hypothesis that large artery stiffness and microvascular damage in CKD patients are related to the damage of brain microcirculation reflected by impaired cognitive function. A cross-sectional study enrolled 151 patients (mean age 58.4 years; 64.5% males; 44 patients with CKD stage 1; 47 with stage 2; 25 with stage 3; and 35 with stage 4). Cognitive impairment, assessed by the Mini Mental State Examination (MMSE), the Clock - drawing test (Clock-test), and the Instrumental Activity of Daily Living (IADL), was considered as primary outcome. We measured systolic and pulse pressures at the brachial and aortic sites and cf-PWV. Our patients revealed a significant linear deterioration in all the domains of cognitive function according to CKD stages. High values of cf-PWV (P = 0.029) and aortic pulse pressure (aPP) (P < 0.026) were independent determinants of cognitive decline assessed by the MMSE. The present trial supports the hypothesis of an interaction between the kidney, large artery damage, central pressure pulsatility, and the injury of brain microcirculation. In clinical practice, cf-PWV and aPP measurements may help to predict cognitive decline. Whether the reduction in aortic stiffness following an aggressive treatment translates into improved cognitive outcomes remains to be determined.

Alterations in arterial blood parameters in patients with liver cirrhosis and ascites.

In cirrhotic patients, in addition to hepatocytes and Kuppfer cells dysfunction circulatory anatomic shunt and ventilation/perfusion (V(A)/ Q) ratio abnormalities can induce decrease in partial pressure of oxygen in arterial blood (PaO(2)), in oxygen saturation of hemoglobin (SaO(2)) as well as various acid-base disturbances. We studied 49 cases of liver cirrhosis (LC) with ascites compared to 50 normal controls. Causes were: posthepatic 37 (75.51%), alcoholic 7 (14.24%), cardiac 2 (4.08%), and cryptogenic 3 (6.12%). Complications were: upper gastrointestinal bleeding 24 (48.97), hepatic encephalopathy 20 (40.81%), gastritis 28 (57.14%), hepatoma 5 (10.2%), renal hepatic syndrome 2 (4.01%), HbsAg (+) 24 (48.97%), and hepatic pleural effusions 7 (14.28%). Average PaO(2) and SaO(2) were 75.2 mmHg and 94.5 mmHg, respectively, compared to 94.2 mmHg and 97.1 mmHg of the control group, respectively (p value in both PaO(2) and SaO(2 )was p<0.01). Respiratory alkalosis, metabolic alkalosis, metabolic acidosis, respiratory acidosis and metabolic acidosis with respiratory alkalosis were acid-base disturbances observed. In conclusion, portopulmonary shunt, intrapulmonary arteriovenous shunt and V(A)/Q inequality can induce a decrease in PaO(2) and SaO(2) as well as various acid-base disturbances. As a result, pulmonary resistance is impaired and patients more likely succumb to infections and adult respiratory distress syndrome.