BACKGROUND AND PURPOSE:We aimed to investigate the association between fluoxetine use and the survival of hospitalised coronavirus disease (COVID-19) pneumonia patients.METHODS:This retrospective case-control study used data extracted from the medical records of adult patients hospitalised with moderate or severe COVID-19 pneumonia at the Uzsoki Teaching Hospital of the Semmelweis University in Budapest, Hungary between 17 March and 22 April 2021. As a part of standard medical treatment, patients received anti-COVID-19 therapies as favipiravir, remdesivir, baricitinib or a combination of these drugs; and 110 of them received 20 mg fluoxetine capsules once daily as an adjuvant medication. Multivariable logistic regression was used to evaluate the association between fluoxetine use and mortality. For excluding a fluoxetine-selection bias potentially influencing our results, we compared baseline prognostic markers in the two groups treated versus not treated with fluoxetine.RESULTS:Out of the 269 participants, 205 (76.2%) survived and 64 (23.8%) died between days 2 and 28 after hospitalisation. Greater age (OR [95% CI] 1.08 [1.05-1.11], p<0.001), radiographic severity based on chest X-ray (OR [95% CI] 2.03 [1.27-3.25], p=0.003) and higher score of shortened National Early Warning Score (sNEWS) (OR [95% CI] 1.20 [1.01-1.43], p=0.04) were associated with higher mortality. Fluoxetine use was associated with an important (70%) decrease of mortality (OR [95% CI] 0.33 [0.16-0.68], p=0.002) compared to the non-fluoxetine group. Age, gender, LDH, CRP, and D-dimer levels, sNEWS, Chest X-ray score did not show statistical difference between the fluoxetine and non-fluoxetine groups supporting the reliability of our finding.CONCLUSION:Provisional to confirmation in randomised controlled studies, fluoxetine may be a potent treatment increasing the survival for COVID-19 pneumonia.

Paradoxically, higher serum levels of osteoprotegerin (OPG: a vascular calcification inhibitor) have been associated with increased arterial stiffness, risk of cardiovascular disease and all-cause mortality. A few studies reported that post-transplant OPG levels are associated with mortality in kidney transplant (KT) recipients. In this study, this association was assessed in a cohort of prevalent KT recipients, adjusting for previously untested potential confounders, including fibroblast growth factor 23 (FGF23) and interleukin 6 (IL-6). Socio-demographic and clinical parameters, medical and transplant history, and laboratory data were collected from 982 prevalent KT recipients. The association between serum OPG and all-cause mortality over a 6-year follow-up period was examined using Kaplan-Meier survival curves and multivariable-adjusted Cox regression models. Participants with high serum OPG were more likely female, older, deceased donor KT recipients and have more comorbidity, lower eGFR, higher FGF23, higher IL-6, and longer dialysis vintage. Each 1 pmol/l higher serum OPG level was associated with a 49% higher risk of mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.49 [1.40-1.61]). This association persisted after adjusting for confounders (HR [95% CI]: 1.20 [1.10-1.30]). In conclusion, serum OPG was associated with all-cause mortality independent of several novel confounders in prevalent KT recipients.

Objective: The role of biochemical and functional markers of microvascular dysfunction to predict cardiovascular outcomes in nondialyzed chronic kidney disease (CKD) remains unclear. In this prospective cohort study, we assessed whether biochemical [serum level of angiopoietin-2 (Ang-2), asymmetric and symmetric dimethylarginin] and functional (laser Doppler flowmetry) measures of microvascular function predicted cardiovascular events, cardiovascular and all-cause mortality in CKD patients.Methods: Postocclusive reactive hyperemia area (PORHHA), acetylcholine and sodium nitroprusside-mediated flow changes were estimated by laser Doppler flowmetry, and Ang-2, asymmetric and symmetric dimethylarginin were assessed in 105 CKD patients at baseline. Multiple failure time Cox-regression analyses with backward elimination were performed to determine the predictors of the combined endpoint of cardiovascular mortality and cardiovascular events or all-cause mortality and cardiovascular events during a median of 66.6 (interquartile range 39.8-80.4) months of follow-up.Results: In univariate models lnAng-2 and lnPORH(HA) both predicted the cardiovascular outcome besides age, diabetes, baseline cardiovascular disease, brachial pulse pressure and log C-reactive protein. In multivariate analysis lnPORHHA [hazard ratio: 0.66 (95% confidence interval: 0.49-0.89) per ln(mU s)], age [1.03 (1.01-1.06) per year], log C-reactive protein [1.31 (1.06-1.64) per ln(mg/l)] and diabetes [3.33 (1.70-6.53)] remained significant predictors of the cardiovascular outcome, whereas lnAng-2 did not enter the model. Neither of the microvascular variables were an independent predictor of all-cause mortality and cardiovascular events.Conclusion: Among the functional and biochemical microvascular parameters PORHHA seems to improve cardiovascular risk assessment in CKD. Nevertheless the robustness of traditional risk factors seems to outweigh the role of microvascular biomarkers on all-cause mortality and cardiovascular events at this time.

Pulse pressure (PP) reflects increased large artery stiffness, which is caused, in part, by arterial calcification in patients with chronic kidney disease. PP has been shown to predict both cardiovascular and cerebrovascular events in various patient populations, including kidney transplant (KTX) recipients. Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in hemodialysis patients. Here we tested the hypothesis that OPG is associated with increased pulse pressure. We cross-sectionally analyzed the association between serum OPG and PP in a prevalent cohort of 969 KTX patients (mean age: 51+/-13 years, 57% male, 21% diabetics, mean eGFR 51+/-20 ml/min/1.73 m(2)). Independent associations were tested in a linear regression model adjusted for multiple covariables. PP was positively correlated with serum OPG (rho = 0.284, p < 0.001). Additionally, a positive correlation was seen between PP versus age (r = 0.358, p < 0.001), the Charlson Comorbidity Index (r = 0.232, p < 0.001), serum glucose (r = 0.172, p < 0.001), BMI (r = 0.133, p = 0.001) and serum cholesterol (r = 0.094, p = 0.003). PP was negatively correlated with serum Ca, albumin and eGFR. The association between PP and OPG remained significant after adjusting for multiple potentially relevant covariables (beta = 0.143, p < 0.001). We conclude that serum OPG is independently associated with pulse pressure in kidney transplant recipients.

Disorders of bone and mineral metabolism affect almost all patients with advanced chronic kidney disease (CKD). High prevalence of decreased bone mineral density has been reported in this population; however, the role and diagnostic utility of bone density measurements are not well established. The incidence of bone fractures is high in patients with ESRD, but the association between fractures and bone density is not obvious. A recent meta-analysis suggested that decreased density at the radius might be associated with higher overall fracture risk. Changes in bone mineral density reflect several underlying pathological processes, such as vitamin D deficiency, estrogen deficiency and changes in bone turnover. The response of bone to these factors and processes is not uniform: it can vary in different compartments of the same bone or in different bones of the skeleton. Therefore, it is important to differentiate between the various types of bone. This may be possible by proper selection of the measurement site or using methods such as quantitative bone computed tomography. Previous studies used different methods and measured bone mineral density at diverse sites of the skeleton, which makes the comparison of their results very difficult. The association between changes in bone mineral metabolism and cardiovascular mortality is well known in ESRD patients. Studies also suggest that low bone density itself might be an indicator for high risk of cardiovascular events and poor overall outcome in this population. Some of the risk factors of low bone mineral density, such as vitamin D or estrogen deficiency, are potentially modifiable. Further studies are needed to elucidate if interventions modifying these risk factors will have an impact on clinical outcomes. In this review, we discuss the options for and problems of assessment of bone density and summarize the literature about factors associated with low bone density and its link to clinical outcomes in patients on maintenance dialysis.

Korabbi vizsgalatok eredmenyei alapjan az erfali tagulekonysag parameterei osszefuggest mutatnak a cardiovascularis mortalitassal hemodializalt betegekben. A kulonboző parameterek relativ prognosztikus erteket ugyanakkor egy kozos kohorszban eddig nem vizsgaltak. Modszer: Dializis előtt es utan 98 betegnel mertuk a carotis-femoralis pulzushullam terjedesi sebesseget, a carotis augmentacios indexet, a carotis pulzusnyomasat es a carotis-brachialis pulzusnyomas amplifikaciojat. A betegeket 29 honapig (median) (tartomany 1–35) kovettuk, majd a cardiovascularis mortalitas es a kiindulaskor mert tagulekonysagi parameterek kozotti osszefuggest vizsgaltuk log-rank tesztek, illetve a korhoz, diabeteshez es korabban meglevő cardiovascularis megbetegedeshez illesztett Cox-fele regresszios modellek alkalmazasaval. Eredmenyek: A kovetes alatt 40 beteg halt meg (mortalitasi rata 20,7/100 betegev), koztuk 25-en cardiovascularis ok kovetkezteben. A dializis előtt es utan mert pulzushullam-terjedesi sebesseget tercilisei, illetve a dializis előtt mert pulzusnyomas-amplifikacio tercilise szignifikans osszefuggest mutattak a cardiovascularis mortalitassal (log-rank p-ertekek 0,012 es 0,011 a pre- es posztdializis pulzushullam-terjedesi sebesseg, illetve <0,001 es 0,321 a pre- es posztdializis pulzusnyomas-amplifikacio eseten). Az augmentacios indexek, illetve a carotispulzusnyomas-ertekek nem alltak osszefuggesben a cardiovascularis mortalitassal. Cox-modellben az 1 m/s-mal gyorsabb pre- es posztdializis pulzushullam-terjedesi sebessegehez tartozo relativ riziko 1,24 (1,07–1,44) es 1,17 (1,06–1,28) volt. 10%-kal kisebb predializispulzusnyomas-amplifikacioval jaro rizikonovekedes 41% (3–92%) volt. Egy kozos modellben vizsgalva mind a predializispulzushullam-terjedesi sebesseg, mind a pulzusnyomas-amplifikacio szignifikans osszefuggest mutatott a cardiovascularis tulelessel [relativ riziko: 1,23 (1,07–1,42) es 1,39 (1,02–1,89)]. Kovetkeztetes: Hemodializalt betegekben az erfali tagulekonysagot leiro kulonboző parameterek kozul a pulzushullam-terjedesi sebesseg a meres idejetől fuggetlen, konzekvens osszefuggest mutat a cardiovascularis mortalitassal. Ugyanakkor a predializispulzusnyomas-amplifikacios ertek tovabbi prognosztikus informaciot hordoz. | Previous studies demonstrated that different parameters of arterial stiffness are related to cardiovascular mortality in hemodialysis patients. The relative prognostic value of these parameters has not previously been evaluated in one cohort. Patients and Methods: : Carotid-femoral pulse wave velocity, carotid augmentation index, carotid pulse pressure and carotid-brachial pulse pressure amplification were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1–34) and the association of these parameters with cardiovascular mortality was assessed using log-rank tests and Cox proportional hazards regressions. Results: During follow-up, 40 patients died (mortality rate 20.7/100 patient-year), of which 25 died of cardiovascular causes. Increasing pre- and postdialysis pulse wave velocity tertiles and decreasing predialysis pulse pressure amplification tertiles were significantly related to cardiovascular mortality (p-values are 0.012 and 0.011 for pre- and postdialysis pulse wave velocity, and <0.001 and 0,321 for pre- and postdialysis pulse pressure amplification, respectively). Neither the carotid augmentation index nor carotid pulse pressure was related to cardiovascular mortality. In the Cox-regression, the adjusted hazard ratios for 1 m/s higher pre- and postdialysis pulse wave velocity were 1.24 (1.07–1.44) and 1.17 (1.06–1.28), respectively. The hazard ratio for 10% lower predialysis pulse pressure amplification was 1.41 (1.03–1.92). When included in the same model, both predialysis pulse wave velocity and pulse pressure amplification remained significantly associated with cardiovascular mortality (relative risk: 1.23 [1.07–1.42] and 1.39 [1.02–1.89]). Conclusion: Among different stiffness parameters, pulse wave velocity is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis pulse pressure amplification seems to provide additional prognostic information.

Korábbi vizsgálatok eredményei alapján az érfali tágulékonyság paraméterei összefüggést mutatnak a cardiovascularis mortalitással hemodializált betegekben. A különböző paraméterek relatív prognosztikus értékét ugyanakkor egy közös kohorszban eddig nem vizsgálták.Módszer:Dialízis előtt és után 98 betegnél mértük a carotis-femoralis pulzushullám terjedési sebességét, a carotis augmentációs indexét, a carotis pulzusnyomását és a carotis-brachialis pulzusnyomás amplifikációját. A betegeket 29 hónapig (medián) (tartomány 1–35) követtük, majd a cardiovascularis mortalitás és a kiinduláskor mért tágulékonysági paraméterek közötti összefüggést vizsgáltuk log-rank tesztek, illetve a korhoz, diabeteshez és korábban meglévő cardiovascularis megbetegedéshez illesztett Cox-féle regressziós modellek alkalmazásával.Eredmények:A követés alatt 40 beteg halt meg (mortalitási ráta 20,7/100 betegév), köztük 25-en cardiovascularis ok következtében. A dialízis előtt és után mért pulzushullám-terjedési sebességet tercilisei, illetve a dialízis előtt mért pulzusnyomás-amplifikáció tercilise szignifikáns összefüggést mutattak a cardiovascularis mortalitással (log-rank p-értékek 0,012 és 0,011 a pre- és posztdialízis pulzushullám-terjedési sebesség, illetve <0,001 és 0,321 a pre- és posztdialízis pulzusnyomás-amplifikáció esetén). Az augmentációs indexek, illetve a carotispulzusnyomás-értékek nem álltak összefüggésben a cardiovascularis mortalitással. Cox-modellben az 1 m/s-mal gyorsabb pre- és posztdialízis pulzushullám-terjedési sebességéhez tartozó relatív rizikó 1,24 (1,07–1,44) és 1,17 (1,06–1,28) volt. 10%-kal kisebb predialízispulzusnyomás-amplifikációval járó rizikónövekedés 41% (3–92%) volt. Egy közös modellben vizsgálva mind a predialízispulzushullám-terjedési sebesség, mind a pulzusnyomás-amplifikáció szignifikáns összefüggést mutatott a cardiovascularis túléléssel [relatív rizikó: 1,23 (1,07–1,42) és 1,39 (1,02–1,89)].Következtetés:Hemodializált betegekben az érfali tágulékonyságot leíró különböző paraméterek közül a pulzushullám-terjedési sebesség a mérés idejétől független, konzekvens összefüggést mutat a cardiovascularis mortalitással. Ugyanakkor a predialízispulzusnyomás-amplifikációs érték további prognosztikus információt hordoz.

In previous studies, different parameters of arterial stiffness were related to cardiovascular mortality in hemodialysis patients, but their relative prognostic value has not previously been evaluated in 1 cohort. Carotid-femoral pulse wave velocity (PWV), the carotid augmentation index, carotid pulse pressure (CPP) and carotid-brachial pulse pressure amplification (AMP) were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1–34) and the association of these parameters with cardiovascular mortality were assessed using log-rank tests and Cox proportional hazards regressions. During follow-up, 25 patients died of cardiovascular causes. Increasing pre- and postdialysis PWV tertiles and decreasing predialysis AMP tertiles were significantly related to cardiovascular mortality (p = 0.012 and 0.011 for PWV, respectively; < 0.001 for AMP). Neither the carotid augmentation index nor carotid pulse pressure were related to cardiovascular mortality. The adjusted hazard ratios for 1 m/s higher pre- and postdialysis PWV were 1.24 (1.07–1.44) and 1.17 (1.06–1.28), respectively. The hazard ratio for 10% lower predialysis AMP was 1.41 (1.03–1.92). When included in the same model, both predialysis PWV and AMP remained significantly associated with cardiovascular mortality. Among different stiffness parameters, PWV is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis AMP seems to provide additional prognostic information.

Background. Treatment decisions made by patients with chronic kidney disease are crucial in the renal transplantation process. These decisions are influenced, amongst other factors, by attitudes towards different treatment options, which are modulated by knowledge and perceptions about the disease and its treatment and many other subjective factors. Here we study the attitude of dialysis patients to renal transplantation and the association of sociodemographic characteristics, patient perceptions and experiences with this attitude.Methods. In a cross-sectional study, all patients from eight dialysis units in Budapest, Hungary, who were on haemodialysis for at least 3 months were approached to complete a self-administered questionnaire. Data collected from 459 patients younger than 70 years were analysed in this manuscript.Results. Mean age of the study population was 53 +/- 12 years, 54% were male and the prevalence of diabetes was 22%. Patients with positive attitude to renal transplantation were younger (51 +/- 11 versus 58 +/- 11 years), better educated, more likely to be employed (11% versus 4%) and had prior transplantation (15% versus 7%)(P < 0.05 for all). In a multivariate model, negative patient perceptions about transplantation, negative expectations about health outcomes after transplantation and the presence of fears about the transplant surgery were associated, in addition to incre- asing age, with unwillingness to consider transplantation.Conclusions. Negative attitudes to renal transplantation are associated with potentially modifiable factors. Based on this we suggest that it would be necessary to develop standardized, comprehensible patient information systems and personalized decision support to facilitate modality selection and to enable patients to make fully informed treatment decisions.

Experimental and clinical trials in the field of bone biology helped to clarify the role of receptors, which belong to the tumor necrosis factor family, such as osteoprotegerin and receptor activator of nuclear factor kappaB (RANK), in the regulation of bone remodeling. The ligand of the receptor activator of nuclear factor kappaB (RANKL) is a stimulator of bone resorption, while osteoprotegerin is the soluble "decoy" receptor to RANKL, protecting thereby bone from resorption. Pathological states of bone remodeling (like osteoporosis) are associated with imbalance in the activity of osteoprotegerin and the receptor activator of nuclear factor kappaB. Recent studies, however, also indicate that the osteoprotegerin/RANKL/RANK system has important roles in the regulation of the immune and vascular system as well. In this review we summarize the function and regulation of osteoprotegerin, its role in pathological states--primarily in cardiovascular diseases--and its relevance as a marker of cardiovascular risk. Finally, we present our prospective trial performed among the chronic dialyzed patients, where we examined the association between the cardiovascular mortality, osteoprotegerin levels and the arterial stiffness.

A csontbiologia teren vegzett vizsgalatok vezettek a tumornekrozis-faktorok csaladjaba tartozo receptorok, igy az osteoprotegerin es a receptor activator of nuclear factor κB (RANK) szerepenek tisztazasahoz a csontatepules folyamatanak szabalyozasaban. A RANK receptor ligandja (RANKL) a csontreszorpcio stimulatora, mig az osteoprotegerin a csont keringő, szolubilis protektora. A csontatepules koros allapotai (igy az osteoporosis is) osszefuggnek az osteoprotegerin es a RANKL kozti egyensulyi allapot megbomlasaval. Az elmult evek eredmenyei ramutattak arra is, hogy az osteoprotegerin/RANKL/RANK rendszer fontos szerepet jatszik az immun- es a vascularis rendszer szabalyozasaban. Kozlemenyunkben az elsődlegesen „csontprotektor” hatasukent megismert osteoprotegerin funkciojat, szabalyozasat es patologias allapotokban – dontően a cardiovascularis megbetegedesekben – jatszott szerepet, rizikomarkerkent valo alkalmazhatosagat foglaljuk ossze. Vegul kronikus hemodializalt betegeink kozott vegzett prospektiv vizsgalatunkat ismertetjuk, amelyben az ezen betegek cardiovascularis mortalitasa, OPG-szerumszintje es erfali tagulekonysaga kozti osszefuggest vizsgaltuk – pozitiv eredmennyel. | Experimental and clinical trials in the field of bone biology helped to clarify the role of receptors, which belong to the tumor necrosis factor family, such as osteoprotegerin and receptor activator of nuclear factor κB (RANK), in the regulation of bone remodeling. The ligand of the receptor activator of nuclear factor κB (RANKL) is a stimulator of bone resorption, while osteoprotegerin is the soluble “decoy” receptor to RANKL, protecting thereby bone from resorption. Pathological states of bone remodeling (like osteoporosis) are associated with inbalance in the activity of osteoprotegerin and the receptor activator of nuclear factor κB. Recent studies, however, also indicate that the osteoprotegerin/RANKL/RANK system has important roles in the regulation of the immune and vascular system as well. In this review we summarize the function and regulation of osteoprotegerin, its role in pathological states – primarily in cardiovascular diseases – and its relevance as a marker of cardiovascular risk. Finally, we present our prospective trial performed among the chronic dialyzed patients, where we examined the association between the cardiovascular mortality, osteoprotegerin levels and the arterial stiffness.

BACKGROUND:Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in haemodialysis patients. The link between OPG and aortic stiffening--a consequence of arterial calcification--has not been previously evaluated in this population, and it is not known whether OPG-related mortality risk is mediated by arterial stiffening.METHODS:At baseline, OPG and aortic pulse wave velocity (PWV) were measured in 98 chronic haemodialysis patients who were followed for a median of 24 months. The relationship between OPG and PWV was assessed by multivariate linear regression. The role of PWV in mediating OPG related cardiovascular mortality was evaluated by including both OPG and PWV in the same survival model.RESULTS:At baseline mean (standard deviation) PWV was 11.2 (3.3) m/s and median OPG (interquartile range) was 11.1 (7.5-15.9) pmol/L. There was a strong, positive, linear relationship between PWV and lnOPG (P = 0.009, model R(2) = 0.540) independent of covariates. During follow-up 23 patients died of cardiovascular causes. In separate univariate survival models both PWV and lnOPG were related to cardiovascular mortality [hazard ratios 1.31 (1.14-1.50) and 8.96 (3.07-26.16), respectively]. When both PWV and lnOPG were entered into the same model, only lnOPG remained significantly associated with cardiovascular mortality [hazard ratio 1.11 (0.93-1.33) and 7.18 (1.89-27.25), respectively).CONCLUSION:In haemodialysis patients OPG is strongly related to PWV and OPG related cardiovascular mortality risk is, in part, mediated by increased PWV.

BACKGROUND:The validation of ambulatory blood pressure monitoring devices is necessary to obtain information on their accuracy. The objective of the present study was to evaluate the accuracy of the Tensioday oscillometric ambulatory blood pressure monitor according to the protocols of the British Hypertension Society and the Association for the Advancement of Medical Instrumentation (AAMI).DESIGN:We followed the phases recommended by the British Hypertension Society protocol: before-use calibration, in-use assessment, after-use calibration, static device validation and report of the evaluation. However, we expanded on the protocol to accommodate features required by the AAMI.METHOD:The accuracy of calibration of three Tensioday devices was tested before and after the in-use phase when each of three devices was performing 10 24 h sessions of ambulatory monitoring. As all three devices passed these phases, the accuracy of blood pressure measurement was tested in one arbitrarily selected device on 85 subjects for systolic and 85 for diastolic blood pressure values. This was done by comparing three sequential same-arm blood pressure readings obtained by the device with three readings obtained by two observers using standard mercury sphygmomanometer. The comparisons were carried out while resting in the seated, supine and standing positions for all subjects. The results were used to grade the performance of the device according to the British Hypertension Society protocol and to calculate the mean +/- standard deviation of the difference between the device and the observers, as required by the AAMI.RESULTS:The Tensioday device achieved an overall grade of A for both the systolic and diastolic measurements, and had a mean difference compared with the observer-measured blood pressure of 1.4 +/- 5.3/1.0 +/- 4.7 mmHg, which satisfies the AAMI criteria for accuracy. The British Hypertension Society grading did not change when patients with low, medium, and high blood pressure were analysed separately. The AAMI accuracy criteria were fulfilled in the standing and lying positions as well.CONCLUSION:On the basis of these results, the Tensioday ambulatory blood pressure monitoring device can be recommended for clinical use for ambulatory monitoring. The accuracy of the device needs, however, further testing in special situations, such as in pregnancy, in elderly patients and during exercise.