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Abstract Background Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF. Methods KF patients, males (n = 214) and females (n = 107), that had undergone computer tomography (CT) assessment for CAC and AVC were selected from three CKD cohorts. All patients underwent non-contrast multi-detector cardiac CT scanning, with CAC and AVC scoring based on the Agatston method. Baseline biochemical measurements were retrieved from cohort databases, including plasma analyses for inflammation markers (IL-6, TNF, hsCRP) and oxidative stress by skin autofluorescence measuring advanced glycation end-products (AGE), amongst other variables. Results Sex-disaggregated analyses revealed that CAC score was associated with age in both males and females (both p

BackgroundEarly life factors may predict cardiovascular disease (CVD), but the pathways are still unclear. There is emerging evidence of an association of early life factors with apolipoproteins, which are linked to CVD. The study objective was to assess the associations between birth variables and adult apolipoproteins (apoA1 and apoB, and their ratio) in a population-based cohort.MethodsThe LifeGene Study is a prospective cohort comprising index participants randomly sampled from the general population. Blood samples were collected between 2009 and 2016. In this sub-study, we used birth variables, obtained from a national registry for all participants born 1973 or later, including birth weight and gestational age, while adult CVD risk factors included age, sex, body mass index (BMI), lipids, and smoking history. We employed univariate and multivariate general linear regression to explore associations between birth variables, lipid levels and other adult CVD risk factors. The outcomes included non-fasting apoA1 and apoB and their ratio, as well as total cholesterol and triglycerides. A total of 10,093 participants with both birth information and lipoprotein levels at screening were included. Of these, nearly 42.5% were men (n = 4292) and 57.5% were women (n = 5801).ResultsThe mean (standard deviation) age of men was 30.2 (5.7) years, and for women 28.9 (5.8) years. There was an increase of 0.022 g/L in apoA1 levels per 1 kg increase in birth weight (p = 0.005) after adjusting for age, sex, BMI, gestational age, and smoking history. Similarly, there was a decrease of 0.023 g/L in apoB levels per 1 kg increase in birth weight (pConclusionsLower birth weight was associated with an adverse adult apolipoprotein pattern, i.e., a higher apoB/apoA1 ratio, indicating increased risk of future CVD manifestations. The study highlights the need of preconception care and pregnancy interventions that aim at improving maternal and child outcomes with long-term impacts for prevention of cardiovascular disease by influencing lipid levels.

Abstract The effect of metabolic syndrome (MetS) and clusters of its components on central blood pressure (CBP) has not been well characterized. We aimed to describe the effect of MetS and clusters of its components on CBP in a large population and to identify whether this effect differs in men and women. We studied 15,609 volunteers (43% women) from 10 cohorts worldwide who participated in the Metabolic syndrome and Artery REsearch Consortium. MetS was defined according to the NCEP-ATP III criteria (GHTBW, glucose, high-density lipoprotein cholesterol, triglyceride, blood pressure, waist circumference). CBP was measured noninvasively and acquired from pulse wave analysis by applanation tonometry. MetS was associated with a 50% greater odds of having higher CSBP. After controlling for age, male sex, non HDL cholesterol, diabetes mellitus, and mean arterial pressure, only specific clusters of MetS components were associated with a higher CSBP; and some of them were significant in women but not in men. We identified “risky clusters” of MetS variables associated with high CSBP. Future studies are needed to confirm they identify subjects at high risk of accelerated arterial aging and, thus, need more intensive clinical management.

Abstract Kidney failure and associated uraemia have implications for the cardiovascular system, brain, and blood–brain barrier (BBB). We aim to examine BBB disruption, by assessing brain-derived neurotropic factor (BDNF), neuron-specific enolase (NSE) levels, and gut-blood barrier (GBB) disruption by trimethylamine N-oxide (TMAO), in chronic kidney disease (CKD) patients. Additionally, endothelial tight-junction protein expressions and modulation via TMAO were assessed. Serum from chronic kidney disease (CKD) female and male haemodialysis (HD) patients, and controls, were used to measure BDNF and NSE by enzyme-linked immunosorbent assays, and TMAO by mass spectrometry. Immunofluorescent staining of subcutaneous fat biopsies from kidney transplant recipients, and controls, were used to measure microvascular expression of tight-junction proteins (claudin-5, occludin, JAM-1), and control microvasculature for TMAO effects. HD patients versus controls, had significantly lower and higher serum levels of BDNF and NSE, respectively. In CKD biopsies versus controls, reduced expression of claudin-5, occludin, and JAM-1 were observed. Incubation with TMAO significantly decreased expression of all tight-junction proteins in the microvasculature. Uraemia affects BBB and GBB resulting in altered levels of circulating NSE, BDNF and TMAO, respectively, and it also reduces expression of tight-junction proteins that confer BBB maintenance. TMAO serves as a potential candidate to alter BBB integrity in CKD.

Abstract Background Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p

Cardio-pulmonary diseases, which were once regarded as a man's illness, have been one of the leading causes of morbidity and mortality for both men and women in many countries in recent years. Both gender and sex influence the functional and structural changes in the human body and therefore play an important role in disease clinical manifestation, treatment choice, and/or response to treatment and prognosis of health outcomes. The gender dimension integrates sex and gender analysis in health sciences and medical research, however, it is still relatively overlooked suggesting the need for empowerment in the medical research community. Latest advances in the field of cardiovascular research have provided supportive evidence that the application of biological variables of sex has led to the understanding that heart disease in females may have different pathophysiology compared to males, particularly in younger adults. It has also resulted in new diagnostic techniques and a better understanding of symptomatology, while gender analysis has informed more appropriate risk stratification and prevention strategies. The existing knowledge in the pulmonary field shows the higher prevalence of pulmonary disorders among females, however, the role of gender as a socio-cultural construct has yet to be explored for the implementation of targeted interventions. The purpose of this review is to introduce the concept of gender dimension and its importance for the cardiopulmonary continuum with a focus on shared pathophysiology and disease presentation in addition to interrelation with chronic kidney disease. The review presents basic knowledge of what gender dimension means, and the application of sex and gender aspects in cardiovascular medicine with a specific focus on early pulmonary development, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). Early vascular aging and inflammation have been presented as a potential pathophysiological link, with further interactions between the cardiopulmonary continuum and chronic kidney disease. Finally, implications for potential future research have been provided to increase the impact of gender dimension on research excellence that would add value to everybody, foster toward precision medicine and ultimately improve human health.

BackgroundThis study aims to describe associations of obesity and CKD in a Swedish urban population. The impact of fat mass, from bioimpedance analysis, on eGFR based on cystatin C and/or creatinine is studied.Methods5049 participants from Malmö Diet and Cancer Study the cardiovascular arm (MDCS-CV) with available body mass composition (single frequency bioimpedance analysis) and cystatin C measured at baseline were selected. Body mass index (kg/m2) was used to define overweight/obesity. eGFR was calculated using cystatin C (eGFRCYS) and creatinine (eGFRCR) equations: Chronic Kidney Disease Epidemiology Collaboration 2012 (CKD-EPICR, CKD-EPICYS, CKD-EPICR-CYS), eGFRCYS based on Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised equation (LMrev), and Modified Full Age Spectrum creatinine-based equation (EKFCCR). Two different fat mass index (FMI) z-scores were calculated: FMI z-scoreLarsson and FMI z-scoreLee.ResultsLower eGFRCYS and eGFRCR-CYS following multiple adjustments were prevalent in overweight/obese subjects. Increase in FMI z-scoreLarsson or FMI z-scoreLee was related to decrease in predicted CAPA, CKD-EPICYS, CKD-EPICR-CYS and CAPA-LMrev equation.ConclusioneGFRCYS, in contrast to combined eGFRCR-CYS and eGFRCR, demonstrate the strongest association between FMI and kidney function.

Purpose: The study was designed to evaluate clinical and laboratory determinants pulse wave velocity (PWV) ratio in women at the age of 50–65 years without overt cardiovascular disease but having elevated cardiovascular risk, such as hypertension, obesity, diabetes and hypercholesterolemia. Materials and methods: We analyzed data from 1170 women enrolled in the national-wide primary prevention program. Univariate and multivariate linear regression analysis was used to establish independent risk factors in groups based on clinical data, laboratory values, and comorbidities. Arterial stiffness was evaluated using applanation tonometry technique (SphygmoCor). The PWV ratio was calculated by dividing cfPWV to crPWV. Results: In multivariate logistic regression analysis, age (OR = 1.109, p

Aim: To assess a time-dependent change of arterial stiffness gradient (PWVratio calculated by dividing carotid-femoral to carotid-radialPWV), a marker of vascular aging, in high cardiovascular risk cohort. Methods: This cohort study (n = 689) was conducted during the period 2010–2019 at Vilnius University Hospital Santaros Klinikos. Participants were referred by the primary health care institutions according to Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program which recruited men at the age of 40–55 years and women at the age of 50–65 years without overt cardiovascular disease; they underwent a detailed cardiovascular risk assessment and arterial stiffness evaluation and were repeatedly examined after the mean follow-up of 965.63 ± 511.98 days. Results: The cohort was comprised of 40.2% male participants. Cardiovascular risk factors were distributed as follows: 19.5% subjects had diabetes mellitus, 52.69% left ventricular hypertrophy, 95.21% hypertension, 99.13% dyslipidemia. During the follow-up period 52.1% of patients presented PWV ratio increase. In spite of the difference in age between men and women, PWV ratio progression adjusted for follow-up time and age was more pronounced in males (OR 1.72, p = 0.032). In the subanalysis, we found that in men, as compared to women, there was a more pronounced decrease in carotid-radialPWV (p < 0.001). The carotid-femoralPWV increased both in men and in women. Glucose level, abdominal obesity, mean arterial blood pressure, menopause was related to the change of the PWV ratio. Conclusion: In this high cardiovascular risk cohort, the change in arterial stiffness gradient is related to abdominal obesity, mean arterial blood pressure, and menopause.

Vascular calcification (VC) is linked to post-transplant cardiovascular events and hypercalcemia which may influence kidney graft function in the long term. We aimed to evaluate whether pretransplant aortic arch calcification (AoAC) can predict post-transplant cardiovascular or cerebrovascular events (CVEs), and to assess its association with post-transplant plasma calcium levels and renal function in one-year follow-up. Our single-center observational prospective study enrolled 37 kidney transplant recipients (KTR) without previous history of vascular events. Two radiologists evaluated pretransplant AoAC on chest X-ray as suggested by Ogawa et al. in 2009. Cohen’s kappa coefficient was 0.71. The mismatching results were repeatedly reviewed and resulted in consensus. Carotid-femoral (cfPWV) and carotid-radial pulse wave velocity (crPWV) was measured using applanation tonometry before and one year after transplantation. Patient clinical, biochemical data, and cardiovascular/CVE rate were monitored within 1 year. We found out that eGFR1year correlated with eGFRdischarge and calcium based on hospital discharge data (β = 0.563, p = .004 and β = 51.360, p = .026, respectively). Multivariate linear regression revealed that donor age, donor gender, and recipient eGFRdischarge (R-squared 0.65, p = .002) better predict eGFR1year than AoAC combined with recipient eGFRdischarge (R-squared 0.35, p = .006). During 1-year follow-up, four (10.81%) patients experienced cardiovascular events, which were predicted by PWV ratio (HR 7.549, p = .045), but not related to AoAC score (HR 1.044, p = .158). In conclusion, KTR without previous vascular events have quite low cardiovascular/CVE rate within 1-year follow-up. VC evaluated as AoAC on pretransplant chest X-ray together with recipient eGFRdischarge could be related to kidney function in one-year follow-up.

Background and Objectives: Kidney transplant recipients represent a unique population with metabolic abnormalities, altered nutritional and immune status, as well as an imbalanced regulation of adipocytokine metabolism. Leptin is a hormonally active protein mainly produced by fat tissue that modulates appetite, satiety, and influences growth, energy, and bone metabolism. There has been great interest in the role of this hormone in chronic kidney disease-related protein energy wasting; thus, a positive leptin correlation with body mass index and fat mass was confirmed. This study was designed to determine the association of pre and post-kidney transplant leptin concentration with nutritional status and body composition. Materials and Methods: We studied 65 kidney transplant recipients. Nutritional status was evaluated before kidney transplantation and 6 months later using three different malnutrition screening tools (Subjective Global Assessment Scale (SGA), Malnutrition Inflammation Score (MIS), and Geriatric Nutritional Risk Index (GNRI)), anthropometric measurements, and body composition (bioelectrical impedance analysis (BIA)). Demographic profile, serum leptin levels, and other biochemical nutritional markers were collected. Statistical analysis was performed with R software. Results: Median age of the studied patients was 45 years, 42% were females, and 12% had diabetes. Leptin change was associated with body weight (p < 0.001), waist circumference (p < 0.001), fat mass (p < 0.001) and body fat percentage (p < 0.001), decrease in parathyroid hormone (PTH) (p < 0.001) transferrin (p < 0.001), diabetes mellitus (p = 0.010), and residual renal function (p = 0.039), but not dependent on dialysis vintage, estimated glomerular filtration rate (eGFR), or delayed graft function at any time during the study. After adjustment for age and sex, body mass index (BMI) (p < 0.001), fat mass (p < 0.001), and body fat percentage (p < 0.001) were independent variables significantly associated with post-transplant leptin change. Lower leptin values were found both before and after kidney transplantation in the SGA B group. GNRI as a nutritional status tool was strongly positively related to changes in leptin within the 6-month follow-up period. Conclusions: Kidney transplant recipients experience change in leptin concentration mainly due to an increase in fat mass and loss of muscle mass. GNRI score as compared to SGA or MIS score identifies patients in whom leptin concentration is increasing alongside an accumulation of fat and decreasing muscle mass. Leptin concentration evaluation in combination with BIA, handgrip strength measurement, and GNRI assessment are tools of importance in defining nutrition status in the early post-kidney transplant period.

Vascular calcification (VC) is linked to post-transplant cardiovascular events in the long term. We aimed to evaluate whether pretransplant chest X-ray based aortic arch calcification (AoAC) or pulse wave velocity measurement can better predict post- transplant cardiovascular or cerebrovascular events, and to assess the progression of calcification within 2 years. Methods: Our single-center observational longitudinal study enrolled 40 kidney transplant recipients (KTR) without previous history of vascular events (no cardiovascular, cerebrovascular events, no peripheral artery disease). Two radiologists evaluated pretransplant and postransplant (after 2 years) AoAC on chest X-ray by using two different AoAC scales: AoAC grade evaluation [1] and AoAC score as suggested by Ogawa et al. in 2009 [2]. Cohen’s kappa coefficient was 0.75. The mismatching results were repeatedly reviewed and resulted in consensus. Carotid-femoral (cfPWV) and carotid-radial pulse wave velocity (crPWV) was measured using applanation tonometry and the PWV ratio (cfPWV/rPWV) was calculated. Patient clinical, biochemical data and cardiovascular/cerebrovascular event rate were monitored within 2 years. Results: During 2-year follow-up 5 patients experienced cardiovascular events, which were predicted by PWV ratio, but not related to AoAC. In 3 patients, we observed progression of AoAC, in others – AoAC was less evident or remained unchanged in 2-years follow-up. AoAC score [2] could better describe the extent of vascular calcification in KTR. Conclusions: KTR without previous vascular events have quite low cardiovascular/ cerebrovascular event rate within 2-year follow-up, which are better predicted by pretransplant PWV ratio. AoAC postransplant regression is evident even when using simplified chest X- ray scales.

Abstract Background Cardiovascular diseases (CVDs) are the most common cause of death worldwide. CVDs share heterogeneous pathophysiologic mechanisms, one of which includes increased oxidative stress. Main Body Surplus levels of reactive oxygen species induce damage to cellular macromolecules such as DNA, proteins, and lipids. Increased reactive oxygen species result in decreased nitric oxide availability, vasoconstriction, and the development of procoagulant and proinflammatory states in blood vessels. Conclusion Improved knowledge of biomolecular processes triggered by oxidative stress has helped develop tools for assessing oxidative stress markers and applying them in clinical settings. Nevertheless, some research gaps should be filled, specifically by defining the most clinically relevant biomarkers for oxidative stress with high sensitivity and specificity for CVD.

Cardiovascular disease (CVD) remains one of the leading causes for increased morbidity and mortality in chronic kidney disease (CKD). Kidney transplantation is the preferred treatment option for CKD G5. Improved perioperative and postoperative care, personalized immunosuppressive regimes, and refined matching procedures of kidney transplants improves cardiovascular health in the early posttransplant period. However, the long-term burden of CVD is considerable. Previously underrecognized, the role of the complement system alongside innate immunity, inflammaging, structural changes in the glomerular filtration barrier and early vascular ageing also seem to play an important role in the posttransplant management. This review provides up-to-date knowledge on these pathways that may influence the cardiovascular and renal continuum and identifies potential targets for future therapies. Arterial destiffening strategies and the applicability of sodium-glucose cotransporter 2 inhibitors and their role in cardiovascular health after kidney transplantation are also addressed.

Gender refers to the socially constructed roles, behaviours, expressions and identities of girls, women, boys, men and gender diverse people. Gender-related factors are seldom assessed as determinants of health outcomes, despite their powerful contribution. The Gender Outcomes INternational Group: to Further Well-being Development (GOING-FWD) project developed a standard five-step methodology applicable to retrospectively identify gender-related factors and assess their relationship to outcomes across selected cohorts of non-communicable chronic diseases from Austria, Canada, Spain, Sweden. Step 1 (identification of gender-related variables): Based on the gender framework of the Women Health Research Network (ie, identity, role, relations and institutionalised gender), and available literature for a certain disease, an optimal ‘wish-list’ of gender-related variables was created and discussed by experts. Step 2 (definition of outcomes): Data dictionaries were screened for clinical and patient-relevant outcomes, using the International Consortium for Health Outcome Measurement framework. Step 3 (building of feasible final list): a cross-validation between variables per database and the ‘wish-list’ was performed. Step 4 (retrospective data harmonisation): The harmonisation potential of variables was evaluated. Step 5 (definition of data structure and analysis): The following analytic strategies were identified: (1) local analysis of data not transferable followed by a meta-analysis combining study-level estimates; (2) centrally performed federated analysis of data, with the individual-level participant data remaining on local servers; (3) synthesising the data locally and performing a pooled analysis on the synthetic data and (4) central analysis of pooled transferable data. The application of the GOING-FWD multistep approach can help guide investigators to analyse gender and its impact on outcomes in previously collected data.

Background and Objectives: Early vascular aging determines a more rapid course of age-related arterial changes. It may be induced by a proinflammatory state, caused by hyperuricemia and metabolic syndrome and their interrelationship. However, the impact of serum uric acid (SUA) on early arterial stiffening and vascular function remains uncertain. Materials and Methods: A total of 696 participants (439 women aged 50–65 and 257 men aged 40–55) from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program were enrolled in the study. They underwent anthropometric measurements and laboratory testing along with arterial parameters’ evaluation. Quality carotid stiffness (QCS), carotid-radial pulse wave velocity (crPWV), carotid-femoral pulse wave velocity (cfPWV), flow-mediated dilatation (FMD), and carotid intima-media thickness (CIMT) were registered. Results: We found that hyperuricemia was significantly associated with inflammation, registered by high-sensitivity C-reactive protein in both sexes. A very weak but significant association was observed between cfPWV and SUA in men and in women, while, after adjusting for risk factors, it remained significant only in women. A positive, weak, but significant association was also observed for QCS, both right and left in women. No relationship was observed between crPWV, FMD, CIMT, and SUA.

Background. The aim of this paper is to share the initial results of LLDN in high-volume university centre that is performing laparoscopic nephrectomies for other indications. Materials and methods. During 2017, four LLDNs were performed. The transperitoneal approach was used in all cases and the kidney was removed using a suprapubic incision. All donors and recipients were prospectively analysed within six-month follow-up. The patients’ clinical, laboratory, and operation-related data were collected from direct interviews with them and from medical records. All patients signed written informed consent. Results. One male and three females donated their left kidneys by using the LLDN technique. The mean age was 58 ± 9 years; two of them with a history of previous cholecystectomy. All donated kidneys had a single renal artery and renal vein. Pre-operative average eGFR was 94.2 ± 7.1 ml/min/1.73 m2, immediately after LLDN 57.5 ± 10.3 ml/min/1.73 m2, after one month 56.0 ± 9.1 ml/min/1.73 m2. There were no intraoperative complications; surgery duration was 223.75 ± 21.74 min, the cold ischemia time was 77.5 ± 28.77 min, and the warm ischemia time 6.37 ± 3.14 min. There was one postoperative donor complication, one case of acute kidney injury, and one case of prolonged postoperative abdominal pain. The only recipient complication was one case of acute kidney rejection; there were no cases of delayed graft function. Conclusions. Our initial experience confirms that LLDN is an approach that is easy to learn, especially in a high-volume university hospital with expertise in performing laparoscopic nephrectomies for other indications.

Background. Gastric antral vascular ectasia (GAVE) is currently recognized as an important cause of upper gastrointestinal (GI) haemorrhage, being responsible for about 4% of non-variceal upper GI haemorrhages and typically presents in middle-aged females. GAVE, also called “watermelon stomach”, is diagnosed through esophagogastroduodenoscopy and is characterized by the presence of visible columns of red tortuous enlarged vessels along the longitudinal folds of the antrum. The pathogenesis is still obscure and many hypotheses have been proposed such as mechanical stress, humoral and autoimmune factors. In the last two decades, numerous therapeutic strategies have been proposed, including surgical, endoscopic, and medical choices, yet successful treatment of GAVE continues to be a challenge. Currently, given the rapid response, safety, and efficacy, endoscopic ablative modalities have largely usurped medical treatments as first-line therapy, particularly using argon plasma coagulation. The actual GAVE prevalence in patients with end-stage renal disease (ESRD) is not clear, yet in difficult cases it should be considered as a cause of erythropoietin resistance. Case presentation. We report four clinical cases of GAVE syndrome patients diagnosed with stage 4 to 5 chronic kidney disease. All patients presented with anaemia and GI haemorrhage, the origin of which turned out to be GAVE syndrome. Conclusions. GAVE syndrome is a serious condition in ESRD patients, especially in those presenting with treatment-refractory anaemia. Realization of its aetiology and characteristics is essential to suspect, diagnose, and treat gastric ectasia. Only proper diagnosis and well-timed disease treatment can significantly improve a patient’s medical condition and future prognosis.