Background/Objectives: Advanced Parkinson's disease is characterized by severe motor fluctuations and disabling dyskinesias that often become refractory to conventional oral dopaminergic therapies. Methods: This study aimed to evaluate the clinical efficacy of levodopa-entacapone-carbidopa intestinal gel (LECIG) in 50 patients initiated during a four-year period at a tertiary movement disorders center. Motor outcomes were analyzed using Wilcoxon signed-rank and McNemar's tests, while multivariable logistic regression was employed to identify predictors of improvement. Results: LECIG initiation significantly reduced mean daily OFF time from 4.63 ± 0.75 to 1.62 ± 1.97 h (p < 0.0001) and total dyskinesia duration by 65% (p < 0.0001). Furthermore, the prevalence of early morning akinesia decreased from 80% to 26%, and delayed ON phenomena were completely eliminated (p < 0.0001). Subgroup analyses indicated that patients with troublesome dyskinesia (≥1 h/day) achieved significantly greater reductions in involuntary movements compared to those with lower baseline dyskinesia levels (p = 0.013). Conclusions: These findings suggest that LECIG provides a meaningful and sustained stabilization of motor complications, highlighting its role as a valuable device-aided therapy in managing advanced Parkinson's disease.

Osteoarthritis is the most common musculoskeletal disorder. It primarily affects people in their mid-40s and older. As the disease progresses, degenerative changes occur in the synovial membrane, subchondral bone, and cartilage. Ultimately, the entire joint and its surrounding tissues become structurally and functionally impaired. Several sets of biochemical markers have been proposed to enable timely diagnosis and anticipate disease progression. However, only a few of these markers are routinely used to evaluate disease activity in subgroups. We conducted a cross-sectional, single-center cohort study of 72 patients with knee osteoarthritis. Diagnoses were established based on clinical data and radiological findings. We examined two Wnt/β-catenin signaling inhibitors, serum DKK-1 and sclerostin, and two bone/cartilage metabolic regulatory factors, RANKL and OPG, correlating these with disease activity and pain scores (WOMAC, VAS, and KOFUS), radiographic stage, inflammatory molecules and indices, and bone mineral density. DKK-1 levels were higher in the intensive pain group (VAS > 5) and positively correlated with the KOFUS throughout the study. This correlation was stronger in individuals with a BMI < 30. Serum DKK-1 levels were higher in patients with lower bone mineral density. No significant modifications in SOST, RANKL, or OPG levels were found in any of the above settings. In our patient cohort with mild-to-moderate knee osteoarthritis (OA), sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were not related to pain or disease activity. In contrast, DKK-1 was an indicator of pain and low-grade flare-ups. Furthermore, DKK-1 was associated with the KOFUS and impaired bone turnover in non-obese subgroups. Confirming these relationships in larger groups of patients would contribute to more efficient use of DKK-1 in disease stratification algorithms.

In addition to the classically accepted pathophysiological features of Alzheimer’s disease (AD), increasing attention is paid to the role of the insulin-resistant state of the central nervous system. Glucagon-like peptide-1 receptor (GLP-1R) agonism demonstrated neuroprotective consequences by mitigating neuroinflammation and oxidative damage. The present review aims to offer a comprehensive overview of the neuroprotective properties of GLP-1R agonists (GLP-1RAs), with a particular focus on experimental animal models of AD. Ameliorated amyloid-β plaque and neurofibrillary tangle formation and deposition following exenatide, liraglutide, and lixisenatide treatment was confirmed in several models. The GLP-1RAs studied alleviated central insulin resistance, as evidenced by the decreased serine phosphorylation of insulin receptor substrate 1 (IRS-1) and restored downstream phosphoinositide 3-kinase/RAC serine/threonine–protein kinase (PI3K/Akt) signaling. Furthermore, the GLP-1RAs influenced multiple mitogen-activated protein kinases (extracellular signal-regulated kinase: ERK; c-Jun N-terminal kinase: JNK, p38) positively and suppressed glycogen synthase kinase 3 (GSK-3β) hyperactivation. A lower proportion of reactive microglia and astrocytes was associated with better neuronal preservation following their administration. Finally, restoration of cognitive functions, particularly spatial memory, was also observed for semaglutide and dulaglutide. GLP-1RAs, therefore, hold promising disease-modifying potential in the management of AD.

Background: Histological signs of carotid atheromatous plaque vulnerability, such as hemorrhage, neovascularization, atherothrombosis, and ulceration, develop against an unstable biological background. Declining renal function contributes to atherosclerotic progression and worsens cardiovascular outcomes. Methods: In a single-center prospective cohort study, we studied 41 endarterectomized patients with severe carotid atherosclerosis. The histological samples were stained with H&E to assess morphology and immunohistochemically labeled with antibodies for CRP and MMP-9 proteins. Complete blood count, the presence of serum biomarkers hsCRP, oxLDL, MCP-1, and MMP-9, and the level of eGFR were determined. Results: Twenty-eight patients with complicated plaques had significantly lower eGFR values: 79.5 (24–110) vs. 94 (69–114) (p = 0.004). Patients with eGFR > 90 mL/min/1.73m2 had a higher incidence of intraplaque hemorrhage and histologic complications of any cause (p = 0.012 and p = 0.003). Patients with bleeding and ulceration from the carotid plaque had a higher neutrophil/lymphocyte ratio. Significantly lower levels of MCP-1 were found in the serum of patients with massive inflammatory infiltrate of the carotid plaques, while serum levels of biomarkers like hsCRP, MMP-9, and oxLDL did not show differences in cases with plaque vulnerability. Conclusions: Signs of plaque vulnerability are associated with reduced renal function, a higher neutrophil/lymphocyte ratio, and lower serum levels of MCP-1 in advanced carotid artery stenosis disease.

Background/Objectives: Low-grade systemic inflammation, characteristic of heart failure (HF), is a nonspecific inflammatory syndrome that affects the entire body. Macrophage migration inhibitory factor 1 (MIF-1) is a pro-inflammatory cytokine, a key mediator of the innate immune response, and may serve as a potential biomarker of monocyte homing and activation in HF with reduced and mildly reduced ejection fraction (HFrEF, HFmrEF). Methods: We evaluated 70 hemodynamically stable patients with left ventricular EF (LVEF) < 50% by means of echocardiography and blood sampling. Results: We report significant correlations between MIF-1, LVEF (r = −0.33, p = 0.005), LV global longitudinal strain (LVGLS, r = 0.41, p = 0.0004), and tricuspid annular plane systolic excursion (TAPSE, r = −0.37, p = 0.001). MIF-1 levels in HFrEF patients were relatively higher, but not significantly different from those observed in HFmrEF. MIF-1 showed significant associations with TAPSE to systolic pulmonary artery pressure ratio (TAPSE/sPAP, p < 0.0001). Also, patients with TAPSE/sPAP < 0.40 mm/mmHg had significantly higher levels of MIF-1 (p = 0.009). Moreover, ischemic cardiomyopathy (ICM) was more frequent in patients with MIF-1 concentrations above 520 pg/mL (57.1% MIF-1hi vs. 28.6% MIF-1lo, p = 0.029). In terms of congestion, MIF-1 showed significant associations with the presence of peripheral edema (p = 0.007), but none was found with self-reported dyspnea (p = 0.307) and New York Heart Association (NYHA) class (p = 0.486). Also, no relationship was reported with N-terminal pro-B-type natriuretic peptide concentrations (NT-proBNP, r = 0.14, p = 0.263). However, the six-minute walk distance was greater in individuals in the MIF-1lo group when compared to those in the MIF-1hi group (404.0 ± 127.4 vs. 324.8 ± 124.1 m, p = 0.010). Conclusions: Beyond identifying inflammatory biomarkers related to disease severity, linking MIF-1 to various pathophysiological mechanisms may highlight the active involvement of the monocyte-macrophage system in HF. This system holds notable significance in congestion-related conditions, acting as a major source of reactive oxygen species that perpetuate inflammation.

Continuous intra-jejunal infusion of levodopa-carbidopa intestinal gel (LCIG) is a long-term proven and effective treatment in advanced Parkinson’s Disease (APD). Efficacy and safety of 16-h administration of LCIG has already been established. Additional benefits of 24-h LCIG administration have been reported in several case series and small clinical studies. The aim of this retrospective study was to compare the characteristics of patients who needed 24-h LCIG from the beginning of the DAT (device-aided treatment) with those who remained with the standard 16-h LCIG treatment and to identify particular motives if any. We initiated LCIG in 150 patients out of which in case of 62 patients (41,3%) due to unsatisfactory initial clinical benefits continuous 24-h LCIG was deemed necessary. Despite the subjective complaints and more severe clinical condition, at baseline evaluation we found statistically significant differences between 16-h LCIG cohort and 24-h LCIG cohort only in case of incidence of freezing (47% vs 65%, p = 0.03) and sudden off (32% vs 48%, p = 0.04). Wake hours/daytime LCIG does not always sufficiently improve the patient's quality of life in some patients due to persistent nighttime troublesome symptoms. Instead of labeling the patient as a non-responder, it is worth trying the 24-h LCIG dosage in a carefully selected group of patients, as there is currently no consensus on reliable criteria that serve the decision in these patients.

Levodopa–entacapone–carbidopa intestinal gel infusion is a relatively new treatment option for advanced Parkinson’s disease. We aimed to describe and analyze the characteristics of de novo levodopa–entacapone–carbidopa intestinal gel therapy in 20 consecutive patients with advanced Parkinson’s disease. We assessed the profile of motor complications by evaluating the following: motor fluctuations, dyskinesias, and the freezing phenomenon at baseline (before the testing period) and before discharge. The treatment significantly reduced the duration of daily hours spent in off time compared with baseline pre-treatment values from a mean of 4.8 ± 0.9 h/day to a mean of 1.4 ± 0.5 h per day (p < 0.001). The duration and severity of peak-dose dyskinesia were also significantly reduced compared with baseline values. Out of the 10 patients who reported freezing, 8 did not present this complication at the pre-discharge assessment. Significant improvements were observed in Hoehn and Yahr scale scores in both the on and off states. The levodopa–entacapone–carbidopa intestinal gel therapy was well tolerated during the follow-up period immediately after initiation. Despite a relatively severe stage of the disease, all patients experienced a significant improvement in motor fluctuations, dyskinesias, and the freezing phenomenon.

Heart failure and mental health conditions frequently coexist and have a negative impact on health-related quality of life and prognosis. We aimed to evaluate depression and anxiety symptoms and to determine the association between psychological distress and cardiac parameters in heart failure with reduced and mildly reduced ejection fraction. A total of 43 patients (33 male, mean age 64 ± 10 years) with heart failure and left ventricular systolic dysfunction (29 with HFrEF, 14 with HFmrEF) underwent comprehensive echocardiographic evaluation. All study participants completed questionnaires for the assessment of depression (PHQ-9), anxiety (GAD-7), and health-related quality of life (MLHFQ). Ten (34%) patients with HFrEF and two (14%) participants with HFmrEF had moderate-to-severe depression symptoms. Significant anxiety symptoms were more frequent in HFrEF (10 vs. 2 patients; 34% vs. 14%). Poor quality of life was also more common among patients with HFrEF (17 vs. 5 patients; 59% vs. 36%), showing higher MLHFQ scores (p = 0.009). Moreover, PHQ-9, GAD-7, and MLHFQ scores showed significant correlations between NYHA class severity and the presence of peripheral edema. The symptoms of dyspnea correlated with both PHQ-9 and MLHFQ scores. Significant correlations were observed between MLHFQ scores and a large number of clinical features, such as exercise capacity, 6MWT distance, the need for furosemide, echocardiographic parameters (LVEDVI, LVESVI, LVEF, LVGLS, SVI), and laboratory variables (albumin, GFR, NT-proBNP). In the multiple linear regression analysis, dyspnea proved to be a significant predictor of higher PHQ-9 and MLHFQ scores, even after adjusting for potential confounders. High symptom burden due to psychological distress is common among patients with HFrEF and HFmrEF. More efficient control of congestion may improve depression, anxiety symptoms, and health-related quality of life.

Vitamin D emerged as an important prognostic biomarker in heart failure (HF), with currently highly debated therapeutic implications. Several trials on vitamin D supplementation in HF showed improvements in left ventricular (LV) remodeling and function and health-related quality of life (HRQoL), which did not translate into mid- to long-term beneficial effects regarding physical performance and mortality. We addressed total 25-hydroxyvitamin D (25(OH)D), serum albumin, and uric acid (UA) levels, focusing mainly on vitamin D deficiency, as potential markers of LV systolic dysfunction in HF with reduced and mildly reduced ejection fraction (HFrEF, HFmrEF). Seventy patients with LVEF < 50% were comprehensively evaluated using ECG, echocardiography, lung ultrasound (LUS), blood sampling, and the six-minute walk test (6MWT). HRQoL was also assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Statistically significant positive correlations were found between LVEF, 25(OH)D, serum UA, and albumin, respectively (p = 0.008, p = 0.009, and p = 0.001). Serum UA (7.4 ± 2.4 vs. 5.7 ± 2.1, p = 0.005), NT-proBNP levels (1090.4 (675.2–2664.9) vs. 759.0 (260.3–1474.8), p = 0.034), and MLHFQ scores (21.0 (14.0–47.0) vs. 14.5 (4.5–25.5), p = 0.012) were significantly higher, whereas 25(OH)D concentrations (17.6 (15.1–28.2) vs. 22.7 (19.5–33.8), p = 0.010) were lower in subjects with severely reduced LVEF. Also, 25(OH)D was independently associated with LVEF in univariate and multiple regression analysis, maintaining its significance even after adjusting for confounders such as age, NT-proBNP, the presence of chronic coronary syndrome, hypertension, and anemia. According to our current findings, 25(OH)D is closely associated with LVEF, further supporting the need to establish correct vitamin D supplementation schemes and dietary interventions in HF. The changes in LVEF, 25(OH)D, serum UA, and albumin levels in HFrEF and HFmrEF indicate a similar pathophysiological background.

BACKGROUND:Atherosclerosis is a progressive disease that results from endothelial dysfunction, inflammatory arterial wall disorder and the formation of the atheromatous plaque. This results in carotid artery stenosis and is responsible for atherothrombotic stroke and ischemic injury. Low-grade plaque inflammation determines biological stability and lesion progression.METHODS:Sixty-seven cases with active perilesional inflammatory cell infiltrate were selected from a larger cohort of patients undergoing carotid endarterectomy. CD68+, iNOS2+ and Arg1+ macrophages and CD31+ endothelial cells were quantified around the atheroma lipid core using digital morphometry, and expression levels were correlated with determinants of instability: ulceration, thrombosis, plaque hemorrhage, calcification patterns and neovessel formation.RESULTS:Patients with intraplaque hemorrhage had greater CD68+ macrophage infiltration (p = 0.003). In 12 cases where iNOS2 predominated over Arg1 positivity, the occurrence of atherothrombotic events was significantly more frequent (p = 0.046). CD31 expression, representing neovessel formation, correlated positively with atherothrombosis (p = 0.020).CONCLUSIONS:Intraplaque hemorrhage is often described against the background of an intense inflammatory cell infiltrate. Atherothrombosis is associated with the presence of neovessels and pro-inflammatory macrophages expressing iNOS2. Modulating macrophage polarization may be a successful therapeutic approach to prevent plaque destabilization.

Osteoarthritis (OA) is a complex disease of whole joints with progressive cartilage matrix degradation and chondrocyte transformation. The inflammatory features of OA are reflected in increased synovial levels of IL-1β, IL-6 and VEGF, higher levels of TLR-4 binding plasma proteins and increased expression of IL-15, IL-18, IL-10 and Cox2, in cartilage. Chondrocytes in OA undergo hypertrophic and senescent transition; in these states, the expression of Sox-9, Acan and Col2a1 is suppressed, whereas the expression of RunX2, HIF-2α and MMP-13 is significantly increased. NF-kB, which triggers many pro-inflammatory cytokines, works with BMP, Wnt and HIF-2α to link hypertrophy and inflammation. Altered carbohydrate metabolism and the upregulation of GLUT-1 contribute to the formation of end-glycation products that trigger inflammation via the RAGE pathway. In addition, a glycolytic shift, increased rates of oxidative phosphorylation and mitochondrial dysfunction generate reactive oxygen species with deleterious effects. An important surveyor mechanism, the YAP/TAZ signaling system, controls chondrocyte differentiation, inhibits ageing by protecting the nuclear envelope and suppressing NF-kB, MMP-13 and aggrecanases. The inflammatory microenvironment and synthesis of key matrix components are also controlled by SIRT1 and mTORc. Senescent chondrocytes represent the functional end stage of hypertrophic differentiation and characteristically upregulate p16 and p21, but also a variety of inflammatory cytokines, chemokines and metalloproteinases, developing the senescence-associated secretory phenotype. Senolysis with dendrobin, miR29b-5p and other agents has been shown to be efficient under experimental conditions, and appears to be a promising tool for the treatment of OA, as it restores COL2A1 and aggrecan synthesis, suppressing NF-kB and destructive metalloproteinases.

BACKGROUND:severe carotid artery stenosis is a major cause of ischemic stroke and consequent neurological deficits. The most important steps of atherosclerotic plaque development, leading to carotid stenosis, are well-known; however, their exact timeline and intricate causal relationships need to be more characterized.METHODS:in a cohort of 119 patients, who underwent carotid endarterectomy, we studied the histological correlations between arterial calcification patterns and localization, the presence of the inflammatory infiltrate and osteopontin expression, with ulceration, thrombosis, and intra-plaque hemorrhage, as direct signs of vulnerability.RESULTS:in patients with an inflammatory infiltrate, aphasia was more prevalent, and microcalcification, superficial calcification, and high-grade osteopontin expression were characteristic. Higher osteopontin expression was also correlated with the presence of a lipid core. Inflammation and microcalcification were significantly associated with plaque ulceration in logistic regression models; furthermore, ulceration and the inflammatory infiltrate were significant determinants of atherothrombosis.CONCLUSION:our results bring histological evidence for the critically important role of microcalcification and inflammatory cell invasion in the formation and destabilization of advanced carotid plaques. In addition, as a calcification organizer, high-grade osteopontin expression is associated with ulceration, the presence of a large lipid core, and may also have an intrinsic role in plaque progression.

Background: Peripheral arterial disease is Occlusive disease of the arteries of the extremity. Common causes are Atherosclerosis (most common), Buerger's disease, vasculitis and other arteritis, thromboembolism etc. Peripheral arterial disease (PAD) is a treacherous disease as it remains asymptomatic for so long. As PAD progresses, it may lead to classical intermittent claudication and critical limb ischemia. DHEAS has been demonstrated to have an antiatherosclerotic effect by prevention of platelet aggregation, uptake of cholesterol and a decrease in the proliferation of vascular smooth muscle cells. Testosterone causes vasodilation of the peripheral arteries by acting on the endothelium of the vessels and in turn results in release of nitric oxide (NO) which is a vasodilator and helps in vasodilation. Testosterone suppresses expression of vascular cell adhesion molecule-1 (proinammatory cytokines), anti-inammatory factors by its derivative 5-dihydrotestosterone which is the earliest step in atherosclerosis. Interestingly Testosterone and DHEAS also has benecial effects on cardiac ischemia, angina and chronic heart failure. The aim of this study is to look for any relationship of Testosterone and DHEAS in Peripheral Arterial Disease. Total 50 patients both inpatients and out Methods: patients were studied. The period of study was from September 2016 to June 2018. Patients who were proven to have peripheral arterial disease on colour doppler were taken for study. The study was done to look if any relationship is present between serum testosterone and dehydroepiandrosterone sulfate (DHEA-S) in a peripheral arterial disease patients. Data were documented and stored in a proper database format. At the end of data collection from the samples, data analysis was done using SPSS 16 software and appropriate tests of signicance were applied. For categorical variables Chi-square test and Fischer's Exact test was used. For comparing two groups of mean student's t-test was used. To correlate more than two continuous data Pearson and Spearman Correlation Coefcient was used. P value <0.05 considered as statistically signicant. Our results showed that total serum testosterone Results: and DHEA-S were not signicantly decreased in PAD patients in comparison to the control group. We could not observe any signicant correlation. These results express that there is no signicant correlation Conclusion: of Serum Testosterone and Dehydroepiandosterone with Peripheral arterial Disease. In our study there are signicant correlations with inammatory markers (C reactive protein, Interleukin6, Homocysteine) Lipid prole (cholesterol, Triglyceride, HDL, VLDL) and HbA1C with serum Testosterone and Dehydroepiandosterone in Peripheral Arterial Disease

Advanced Parkinson’s disease (APD) cannot be treated efficiently using the classical medications however, in recent decades invasive therapeutical methods were implemented and confirmed as effective. One of these methods makes it possible to continue the levodopa (LD) supplementation as a gel administered directly into the upper intestine. However, there are a number of unanswered questions regarding this method. Therefore, we retrospectively analyzed a 10-year period of selected patients that were treated with levodopa/carbidopa intestinal gel (LCIG). We included all APD patients with motor fluctuations and dyskinesia at presentation. LCIG treatment was started in 150 patients: on average these patients received LD for 10.6 ± 4.4 years with a frequency of 5.2 ± 1.0/day until the introduction of LCIG. The estimated and the real LCIG dose differed significantly (mean: 1309 ± 321 mg vs. 1877 ± 769 mg). The mean duration of LCIG administration was 19.8 ± 3.6 h, but in a number of 62 patients we had to administer it for 24 h, to maximize the therapeutic benefit. A carefully and individually adjusted LCIG treatment improves the quality of life of APD patients, but questions remain unresolved even after treating a large number of patients. It is important to share the ideas and observations based on the real-life experience related to the optimal timing, the appropriate dose and duration of administration of the LCIG.

Peripheral arterial disease (PAD) is frequently associated with atherosclerotic manifestations of the carotids and coronaries. Polyvascular involvement and low ankle–brachial index predict major cardiovascular events and high mortality. Cathepsin S (Cat S) promotes the inflammatory pathways of the arterial wall, while Cystatin C (Cys C) functions as its inhibitor; therefore, Cys C was proposed to be a biomarker of progression in PAD. In a single-center observational study, we investigated the correlations of serum Cys C and Cat S/Cys C ratio in a group of 90 PAD patients, predominantly with polyvascular involvement. Cys C and Cat S/Cys C were associated with ankle–brachial index (ABI) scores <0.4 in univariate and multiple regression models. Furthermore, both markers correlated positively with the plasma Von Willebrand Factor Antigen (VWF: Ag) and Von Willebrand Factor collagen-binding activity (VWF: CB). In addition, Cat S/Cys C was significantly decreased, whereas Cys C increased in subjects with three-bed atherosclerotic involvement. According to our results, high serum Cys C and low Cat S/Cys C ratios may indicate severe peripheral arterial disease and polyvascular atherosclerotic involvement.

Abstract Alzheimer’s disease represents one of the unsolved problems of modern medicine, which assumes a significant financial burden in the research, medical, and social fields as well. Treatments intended for preventing and slowing neurodegenerative processes are the subject of a considerable amount of research and clinical trials, but the results are still insignificant regarding the clinical applicability. Initially, we believed that slow neurodegeneration can be traced back entirely to the accumulation of β-amyloid proteins with atypical structure and behavior in certain areas of the brain. This theory was constantly supplemented by the observation of intracellularly aggregating neurofibrillary tangles and the formulation of neuroinflammatory mechanisms. In this regard Alzheimer’s disease-associated neuroinflammation is an immunological response to the presence of β-amyloid oligomers, which initially leads to microglial activation and inflammatory cytokine release. Over time, this process becomes chronic, extending to astrocytes, neurons, and brain microvascularization, and leading to functional impairment, which is clinically manifested in cognitive and memory deficits. The defined central role of neuroinflammation was overturned by the therapeutic failure of drugs with anti-inflammatory capacity. Subsequently, our knowledge was completed by the recognition of how oxidative stress and the altered brain insulin signaling influences metabolic processes, opening new perspectives for drug development. Despite this, new drug candidates are successively failing, as complex regulatory mechanisms have been identified that question the initial triggering role of the β-amyloid and the final impairing effect of the inflammation. The aim of this study is to summarize and present the biochemical and pathophysiological knowledge that contributed to the currently available more comprehensive picture and a more detailed understanding of the processes of Alzheimer’s disease. Properly planned and executed preclinical experiments are essential to establish further clinical conclusions. By the comparison of the currently used rodent models, we tried to draw attention to the complexity of animal experiments and the importance of their multi-level (behavioral, biochemical, histological) evaluation.

Összefoglaló. Bevezetés: Az előrehaladott Parkinson-kór bizonyos fázisában a motoros komplikációk már nem befolyásolhatók hatékonyan a hagyományos orális, illetve transdermalis gyógyszerekkel. Ilyenkor meg kell fontolni, komplex felmérési és döntési folyamatot követően, az invazív eszközös terápiák bevezetését. Célkitűzés: A döntéshozatal és a fontosabb klinikai paraméterek elemzése levodopa-karbidopa intestinalis géllel kezelt betegeinknél az elfogadás időtartamának függvényében. Módszer: Retrospektíven vizsgáltuk azon betegeink adatait, akiknél a marosvásárhelyi 2. Sz. Ideggyógyászati Klinikán 2011. június 1. és 2019. december 31. között vezettük be a levodopa-karbidopa intestinalis géllel történő terápiát. A kezelés elfogadásához szükséges időintervallum szerint két csoportot alkottunk: egy hónap vagy annál rövidebb, illetve egy hónapnál több idő az első, célzott kivizsgálás és a tesztelés megkezdése között. Eredmények: A vizsgált időszakban 163 betegnél teszteltük orrszondán a kezelés hatékonyságát, közülük 127 esetben történt meg a terápia véglegesítése. A döntéshozatal 56 betegnél egy hónap vagy annál rövidebb időt, míg 71 betegnél egy hónapnál több időt igényelt. A dyskinesisek átlagos időtartamának szempontjából szignifikáns különbséget találtunk a két csoport között (3,1 ± 0,7 vs. 2,8 ± 0,8 óra, p = 0,02). Az eszközös terápia bevezetése előtti levodopa-átlagadag 821,5 ± 246,6 mg volt, naponta átlagosan 5-ször adagolva. A kiegészítő terápiák alkalmazási arányai: a dopaminagonisták 80,3%-ban, a katechol-O-metiltranszferáz-gátlók 62,2%-ban, illetve a monoaminoxidáz-B-gátlók 68,5%-ban. Az átlagos off időtartam 4,7 ± 1,1 óra volt, és 85 betegünknél tapasztaltunk 2,9 ± 0,8 óra átlag-időtartamú dyskinesist. Következtetés: Hamarabb fogadják el az eszközös terápiát azok az előrehaladott Parkinson-kóros betegek, akiknek hosszabb időtartamú a napi dyskinesisük, illetve régebbi a betegségük. A terápiás irányelvek gyakorlatba ültetésekor figyelembe kell venni a helyi sajátosságokat: a kiegészítő gyógyszerekhez, illetve az eszközös terápiákhoz való hozzáférést. Orv Hetil. 2021; 162(21): 839–847. Summary. Introduction: In advanced stages of Parkinson’s disease, motor complications cannot be effectively controlled with conventional therapies. In such cases, the complex assessment and decision-making process that leads to device-aided therapies should be considered. Objective: To analyze the decision-making and key clinical parameters, as a function of duration of acceptance, patients treated with levodopa-carbidopa intestinal gel. Method: We retrospectively examined the data of patients who started levodopa-carbidopa intestinal gel therapy at the 2nd Department of Neurology Târgu Mureş, between 1 June 2011 and 31 December 2019. Two groups were formed: less than one month and more than one month between the first targeted examination and the start of testing. Results: Therapeutic efficiency was tested with nasal tube on 163 patients, out of whom 127 patients remained on treatment. Decision-making took one month or less for 56 patients and more than a month for 71 patients. Duration of dyskinesias was significantly different between the two groups (3.1 ± 0.7 vs 2.8 ± 0.8 hours, p = 0.02). Mean dose of levodopa prior to the introduction of device-aided therapy was 821.5 ± 246.6 mg, administered 5 times daily. Dopamine agonists were used in 80.3%, catechol-O-methyltransferase inhibitors in 62.2%, and monoamine oxidase-B inhibitors in 68.5% of cases. The mean off-time was 4.7±1.1 hours and data from 85 patients showed 2.9 ± 0.8 hours of dyskinesia. Conclusion: Device-aided therapy is adopted sooner by patients with advanced Parkinson’s disease with longer disease duration and more dyskinesias. Local specificities, such as access to add-on medication and device-aided therapies, must be taken into account when implementing therapeutic guidelines. Orv Hetil. 2021; 162(21): 839–847.

Inflammation has emerged as an important contributor to heart failure (HF) development and progression. Current research data highlight the diversity of immune cells, proteins, and signaling pathways involved in the pathogenesis and perpetuation of heart failure. Chronic inflammation is a major cardiovascular risk factor. Proinflammatory signaling molecules in HF initiate vicious cycles altering mitochondrial function and perturbing calcium homeostasis, therefore affecting myocardial contractility. Specific anti-inflammatory treatment represents a novel approach to prevent and slow HF progression. This review provides an update on the putative roles of inflammatory mediators involved in heart failure (tumor necrosis factor-alpha; interleukin 1, 6, 17, 18, 33) and currently available biological and non-biological therapy options targeting the aforementioned mediators and signaling pathways. We also highlight new treatment approaches based on the latest clinical and experimental research.

Arterial stiffness (AS) is a complex vascular phenomenon with consequences for central hemodynamics and left-ventricular performance. Circulating biomarkers have been associated with AS; however, their value in heart failure is poorly characterized. Our aim was to evaluate the clinical and biomarker correlates of AS in the setting of heart failure with reduced ejection fraction (HFrEF). In 78 hospitalized, hemodynamically stable patients (20 women, 58 men, mean age 65.8 ± 1.41 years) with HFrEF, AS was measured using aortic pulse wave velocity (PWV). Serum OPG, RANKL, sclerostin, and DKK-1 were determined, and the relationships between the clinical variables, vascular-calcification-related biomarkers, and PWV were evaluated by correlation analysis and linear and logistic regression models. OPG and the OPG/RANKL ratio were significantly higher in the group of patients (n = 37, 47.4%) with increased PWV (>10 m/s). PWV was positively correlated with age, left-ventricular ejection fraction, and carotid intima-media thickness (cIMT), and negatively correlated with the glomerular filtration rate. OPG and cIMT were significantly associated with PWV in the logistic regression models when adjusted for hypertension, EF, and the presence of atherosclerotic manifestations. Elevated serum OPG, together with cIMT, were significantly related to increased AS in the setting of HFrEF.

Abstract Background The Wnt/β-catenin signaling pathway plays an important role in endothelial inflammation, vascular calcification, contributing to atherosclerosis development and progression. Sclerostin and Dickkopf-1 (DKK-1) are soluble extracellular canonical Wnt signaling inhibitors frequently associated with atherosclerotic disease. Purpose We investigated the possible association between carotid intima-media thickness (cIMT) and circulating levels of sclerostin and DKK-1 in patients with heart failure with reduced ejection fraction (HFrEF). Methods 65 patients with HFrEF were assigned to one of two groups based on cIMT measurements: 30 patients had normal cIMT, whereas 35 patients showed pathological cIMT. CIMT was assessed by vascular ultrasonography, and values above 0.9 mm were considered abnormal. Serum sclerostin and DKK-1 levels were measured using commercially available ELISA kits. Unpaired t-test and Mann-Whitney test were used for statistical analysis (p<0.05 was considered statistically significant). Results Patients belonging to the group with abnormal cIMT were older (70±9 years vs. 57±12 years, p<0.0001), had higher systolic blood pressure (123±16 mm Hg vs. 112±15 mm Hg, p=0.005), and had more often type 2 diabetes mellitus (40.00% vs. 13.33%, p=0.017). Sclerostin levels were significantly higher in the abnormal cIMT population (537.91±816.69 pg/mL vs. 276.37±173.21 pg/mL, p=0.017), whereas serum DKK-1 concentrations did not differ significantly (398.34±218.73 pg/mL vs. 352.35±188.08 pg/mL, p=0.498). The two groups had similar C-reactive protein levels (1.78±2.77 mg/dL vs. 1.88±2.77 mg/dL, p=0.200), estimated glomerular filtration rates (73.60±22.32 mL/min/1.73m2 vs. 66.25±23.69 mL/min/1.73m2, p=0.254) and body mass index (27.58±4.95 kg/m2 vs. 26.65±5.75 kg/m2, p=0.490). Conclusion Patients with HFrEF and increased cIMT had elevated levels of serum sclerostin. DKK-1 levels did not increase with the progression of cIMT. Further studies with large sample size are needed to establish the involvement of these proteins in vascular calcification and atherosclerosis in the setting of HFrEF. Funding Acknowledgement Type of funding sources: None.