Quality of Life Assessment in Romanian Patients with Spinal Muscular Atrophy Undergoing Nusinersen Treatment.

Spinal muscular atrophy (SMA), identified over a century ago, is characterized by severe muscle wasting and early mortality. Despite its rarity, the high carrier frequency of the responsible genetic mutations and the variability in its manifestations make it a significant research focus. This prospective cross-sectional descriptive study evaluated health-related quality of life (HRQoL) across eight health domains in 43 Romanian SMA patients treated with nusinersen, using the SF-36 questionnaire to analyze influencing factors. The survey was conducted online with informed consent, and the data were analyzed using MedCalc software, employing both parametric and non-parametric statistical tests for accurate interpretation. The results revealed significant variations in HRQoL. Most patients were non-ambulatory (74.4%), reflecting SMA's impact on mobility. Urban residents reported better outcomes, particularly in physical functioning (p = 0.014), which may be attributed to improved access to healthcare services. Younger participants (under 14), represented by proxy responses, noted better general health (p = 0.0072) and emotional well-being (p = 0.0217) compared to older participants. These findings suggest that younger patients or their proxies perceive a better health status, highlighting the need for age-specific approaches in SMA management and the potential optimistic bias associated with proxy reporting on perceived health outcomes.

Bacterial Resistances and Sensibilities in a Tertiary Care Hospital in Romania-A Retrospective Analysis.

The increase in bacterial resistance is currently a global burden for the health care system. In order to evaluate the resistance rates of several bacteria from the most encountered cultures in clinical practice, we performed a retrospective analysis of all of the positive cultures from the year 2021 in a tertiary care hospital in Romania. Our analysis captured 3299 positive cultures. The median age of the patients was 62 years (IQR: 41-71 years old) with a slight predominance among females (53.1%). Overall, the most common cultures were urocultures, wound secretion cultures and blood cultures, and the most common identified bacteria were Escherichia coli, Staphylococcus aureus and Klebsiella spp. Positive cultures with the highest resistance rates were found in the bronchial aspirate cultures, catheter tip cultures, urocultures and blood cultures. Escherichia coli (n = 996) had the highest resistance to ampicillin (19.8%) and trimetoprim-sulfametoxazole (16.4%), while Staphylococcus aureus (n = 698) presented the highest resistance rates to clindamycin (27.4%) and oxaciline (19.7%). Klebsiella (n = 481) presented the highest resistance rates to piperaciline-tazobactam (25.2%) and ampicillin (20.4%), whereas Acinetobacter baumanii (n = 123) presented a resistance rate of more than 50% to carbapenems, gentamicin, ciprofloxacin and ceftazidime. The aim of our study was to identify bacterial resistance rates in order to provide updated clinical data to guide physicians in choosing the best empirical antibiotic treatment, especially in the west part of Romania.

Novel Biomarkers in Evaluating Cardiac Function in Patients on Hemodialysis-A Pilot Prospective Observational Cohort Study.

Chronic kidney disease patients treated by hemodialysis present a high cardiovascular morbidity and mortality. There is an imperative need for novel biomarkers for identifying these patients and to offer possible therapeutically interventions. We performed a prospective observational cohort study on 77 patients in the period of October 2021-October 2023. We measured serum plasma levels of interleukin 1-beta, galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion site. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. The mean age was 61.02 (±11.81) years, with 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54%), and more than two-thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-beta was correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle telesystolic diameter. Galectin 3 values were negatively correlated with aortic valve fibrosis and mitral valve calcifications, and human suppression tumorigenicity factor 2 was negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better assess cardiovascular disease in patients on maintenance hemodialysis.

Time-to-Treatment Delays and Their Prognostic Implications in Pharyngeal Cancer-An Exploratory Analysis in Western Romania.

BACKGROUND: Diagnosis and treatment for pharyngeal cancer are decisive in determining prognosis. Diagnosis delays are frequent, representing a significant cause of avoidable mortality, and an important factor in subpar survival across the continuous HNC care delivery. METHODS: The present study represents a retrospective analysis of medical records from Western Romania, which included 180 patients, to evaluate the impact of time-to-treatment delay on patients diagnosed with pharyngeal cancer. The data analyses were performed using the Kaplan-Meier method R (version 3.6.3) packages, including tidyverse, final-fit, mcgv, survival, stringdist, janitor, and Hmisc. RESULTS: The mean days from diagnosis until the end of treatment were higher for the nasopharynx group. Cox regression analysis regarding diagnosis to treatment duration categories showed an increased risk mortality by 3.11 times (95%CI: 1.51-6.41, p = 0.0021) with a Harrell's C-index of 0.638 (95%CI: 0.552-0.723). The hypopharynx and oropharynx locations increased risk mortality by 4.59 (95%CI: 1.55-13.55) and 5.49 times (95%CI: 1.79-16.81) compared to the nasopharynx location. CONCLUSIONS: The findings of this study led to the conclusion that it seems there is a trend of mortality risk for oropharynx and hypopharynx cancers due to delays in the time to treatment over 70 days, standing as a basis for further research as there is an imperative need for prospective multicenter studies.

Acute Kidney Disease following Acute Kidney Injury in Children-A Retrospective Observational Cohort Study on Risk Factors and Outcomes.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding AKD in children are scarce. The purpose of our study was to explore the risk factors for developing AKD based on exposures and susceptibilities in children with AKI doubled by the biological parameters from the first day of identified AKI. In addition, we followed the trajectory of AKD following an acute kidney injury (AKI) episode in children during hospital admission and after discharge with special considerations towards mortality and progression to new-onset CKD. Methods: We retrospectively evaluated 736 children, ages between 2 and 18 years old, with identified AKI during hospital admission in a tertiary care hospital from west Romania over a 9-year period. Results: AKD incidence following an AKI episode was 17%. Patients who developed AKD were older, with higher baseline serum creatinine, urea, C reactive protein and lower proteins, haemoglobin and sodium levels. In the adjusted model, no biological parameters influenced AKD development. Regarding certain exposures and personal susceptibilities in children with AKI, only anaemia independently increased the risk of AKD development by 2.47 times. However, out of the AKI causes, only the intrinsic causes of AKI independently increased the risk of progressing to AKD (glomerulonephritis by 4.94 and acute tubule-interstitial nephritis by 2.76 times). AKD increased the overall mortality by 2.6 times. The factors that independently increased the risk of CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: Only anaemia, glomerulonephritis and acute tubule-interstitial nephritis increased the risk of AKD development in children with AKI. AKD was an independent risk factor for mortality and new-onset CKD in children.

Acute kidney injury in children: incidence, awareness and outcome-a retrospective cohort study.

The primary objective was to determine the epidemiologic influence of AKI awareness among physicians in a mixt paediatric population, including neonates. This single-centre, multiyear, observational retrospective study included all admitted patients between first of July 2014 and 31 December 2021. AKI was identified in 2194 patients out of the 128,036 hospital admissions with 129,936 serum creatinine measurements. Matching comparisons were used between AKI aware and AKI non-aware patients. The overall incidence of AKI was 1.65%. Stage 1 was identified in 24.24% of the AKI cases, stage 2 in 31.03% and stage 3 in 44.71%. The most prevalent cause of AKI was represented by prerenal AKI in 85.64% of the cases, followed by 12.16% renal causes respectively 2.18% postrenal causes. Exposure to sepsis, critical illness, hypovolemic shock and mechanical ventilation increased mortality by 2.09, 4.69, 4.64- and 4.93-times (p = 0.001). Cancer and heart failure increased mortality by 4.22 (p < 0.001) respectively 2.17 times (p = 0.001). The presence of AKI increased mortality by 79.11 times while only half of the AKI associated deaths were recognized by physicians. AKI increased hospitalization more than 4 times the average stay. AKI awareness was dependent of lower age and severity. Also, awareness increased mortality and prolonged hospitalization. 1 in 3 neonates and 1 in 4 children were AKI aware. The physician's awareness of AKI diagnosis is in general low due to lack of appliance of current guidelines in exploring exposures and susceptibilities for AKI screening.

Kinetic Estimated Glomerular Filtration Rate in Predicting Paediatric Acute Kidney Disease.

Kinetic estimation of glomerular filtration rate (KeGFR) has proved its utility in predicting acute kidney injury (AKI) in both adults and children. Our objective is to assess the clinical utility of KeGFR in predicting AKI severity and progression to acute kidney disease (AKD) in patients already diagnosed with AKI and to examine major adverse kidney events at 30 days (MAKE30). We retrospectively calculated the KeGFR within the first 24 h of identified AKI (KeGFR1) and in the 24 h prior to AKD (KeGFR2) in all admitted children under 18 years old. The cohort consisted of 803 patients with AKI. We proposed a new classification of KeGFR stages, from 1 to 5, and assessed the predictive value of KeGFR stages for AKD development and MAKE30. AKI severity was associated with lower KeGFRs. KeGFR1 and KeGFR2 predicted AKD with AUC values between 0.777 and 0.841 respectively, p < 0.001. KeGFR2 had the best performance in predicting MAKE30 (AUC of 0.819) with a sensitivity of 66.67% and specificity 87.7%. KeGFR1 stage 3, 4 and 5 increased the risk of AKD by 3.07, 6.56 and 28.07 times, respectively, while KeGFR2 stage 2, 3, 4 and 5 increased the risk of AKD 2.79, 3.58, 32.75 and 80.14 times. Stage 5 KeGFR1 and KeGFR2 stages 3, 4 and 5 increased the risk of MAKE30 by 7.77, 4.23. 5.89 and 69.42 times in the adjusted models. KeGFR proved to be a useful tool in AKI settings. KeGFR dynamics can predict AKI severity, duration and outcomes.

Trends in mortality and comorbidities in hemodialysis patients between 2012 and 2017 in an East-European Country: a retrospective study.

PURPOSE: The aim of this study was to evidence trends and changes in mortality, comorbid conditions, prognosis, and causes of death after 5 years of continuous evolution of hemodialysis (HD) patients in Romania. METHODS: We included two cohorts of stable HD patients (901 from 2012 and 1396 from 2017). Both cohorts were followed up for 1 year. The 5-year survivors of the 2012 cohort were identified in 2017 and their data changes were assessed. RESULTS: The 2017 patients were older, with longer time on dialysis, higher serum creatinine and urea levels, and required higher ultrafiltration volume per dialysis. They also had lower hemoglobin, lower C-reactive protein, higher albumin, higher calcium bicarbonate, and higher parathyroidectomy prevalence. The 2017 cohort presented with lower average dialysis flow, less administration of iron sucrose, had more catheters, lower hepatitis C prevalence, higher diabetes mellitus prevalence, higher heart valve calcifications, higher heart rate disorders, higher prevalence of left ventricular hypertrophy, and lower ejection fraction. Cardiovascular disease was the main cause of death in both years (50% in 2012 and 45.6% in 2017), followed by sepsis and cancer. The mortality was higher in 2017 compared to 2012 (14.1 vs 6.6%). The 5-year mortality was 37.2% with an average of 7.44%/year. The risk of death increased with age, higher C-reactive protein, higher phosphate, lower hemoglobin, and lower albumin. CONCLUSION: Cardiovascular disease remains the main causes of death in HD-treated patients but with decreasing trend. Developing regional therapeutic strategies for quality care with early intervention will most likely improve mortality.

Hepatitis C and hepatitis B virus infection in hemodialysis patients after nationwide direct antiviral agents therapy-experience of 10 Romanian HD centers.

PURPOSE: End-stage kidney disease patients (ESKD) receiving hemodialysis (HD) are at a greater risk of hepatitis virus (HV) infections due to the invasive nature of the procedures, frequent hospital stays and surgeries, as well as the immune deficiency status of ESKD. THE AIM: This study was to reassess the hepatitis virus infections prevalence in the HD population in Romania after 5 years of oral DAAs therapy and assess the impact on HD patients' outcomes in two cohorts (2015 and 2019). METHODS: We compared ESKD patients treated with HD in 10 HD centers from the historical regions of Romania in 2015 (n = 1401, Mean age 59.7 ± 12.92 years) with patients treated in the same centers in 2019 (n = 1698, mean age 61 ± 12.93 years). All patients went through HD therapy for more than 90 days. RESULTS: The patients from the 2019 cohort were significantly older (p = 0.005), had a longer duration of HD therapy (p < 0.0001), and had more vascular calcifications (p = 0.015); the crude one-year mortality rate did not differ from the 2015 cohort (9.9 vs. 10.7%, p = 0.46). The prevalence of HBV infection did not differ between the cohorts (4.7% vs. 4.8, p = 0.604) but the prevalence of HCV significantly decreased from 2015 to 2019 (16.9 vs. 10.5%, p < 0.0001). CONCLUSION: After 15 years of a nationwide infection prevention program for HV infections and 5 years of DAAs treatment in Romania, the prevalence of HBV did not change but HCV infections decreased significantly, however, it still remained high.

Chronic kidney disease in cancer patients, the analysis of a large oncology database from Eastern Europe.

INTRODUCTION: Kidney dysfunction is prevalent in oncology patients and has an impact on their treatment and quality of life. The aim of our study was to analyze the prevalence of CKD in a large cohort of several types of cancer patients in an East European Region. MATERIAL AND METHODS: We conducted an observational retrospective cohort study on 5831 consecutive, biopsy-diagnosed cancer patients between January 2019 -December 2020 in the largest oncology hospital and outpatient clinic in Western Romania. 4342 subjects were included in the statistical analysis. RESULTS AND DISCUSSION: From the 24 cancer types, the most prevalent cancers were represented by: breast (22.02%), lung (10.18%) and colonic cancer (9.51%). The prevalence of CKD (G3 -G5) was 12.27% after the first year of follow-up and 13.42 after the second year. The prevalence of CKD was higher in patients with renal (50%), urinary tract (33.6%) and pancreatic cancers (19.6%) and lower in patients with colonic cancers (5.3%) and brain tumors (2.5%). At the end of our 2-year survey period, 0,7% of the CKD cases had an eGFR around 6 ml/min/1.73m2 -an indication for renal replacement therapy. CONCLUSION: Oncology patients have a significantly higher prevalence of CKD compared to the general population, dependent of the age of the patients and the type of cancer. The prevalence of advanced CKD was surprisingly high (stages G4-G5 Pre-Dialysis 22.15%) one third of the CKD- G5 patients having indication for initiation of renal replacement therapy. An onco- nephrology team should be needed for the best medical care of these patients.

Exploring the relation between mortality and left ventricular structure and function in stable hemodialysis treated patients, a longitudinal multicenter cohort study.

Left ventricular (LV) structure and function anomalies are frequent during the CKD continuum and are associated with increased risk of mortality. Cross section and longitudinal ultrasound data are available for advanced CKD and transition to ESKD. Less information is available about LV changes during stable, long-term hemodialysis (HD) treatment. All stable HD patients from 9 HD centers (1034 patients, 671 males, age 58.71 ± 12.94 years) have been enrolled in January 2015. The cohort was followed-up for 4 years, kidney transplantation or death. Yearly, two-dimensional and M-mode continuous and Pulse Doppler echocardiography were performed. During the follow-up, the prevalence of cardiovascular comorbidities significantly increased (p < 0.0001), coronary artery disease (CAD) from 73.5 to 88.8%, peripheral artery disease (PAD) from 29 to 40.9%, cerebral vascular disease (CVD) from 20.4 to 30.8%, heart valves calcification (VC) from 65.6 to 89.3% and left ventricular hypertrophy (LVH) from 67.6 to 76.5%. The mortality risk increased with the presence of CAD (1.59-fold), PAD (1.61-fold), CVD (1.59-fold), and VC (1.77-fold). Mortality risk was increased in those with LVEF < 50% (LVEF 40-49% 1.5-fold and LVEF < 40% 2.3 fold). Among the survivors of the first year, LVEF varied (> 5% decrease, > 5% increase and ± 5% variations). More than 5% increase of LVEF was associated with higher mortality risk (crude 1.5-fold, adjusted 1.43-fold) compared to stationary EF (p = 0.001). Cardiovascular disease progresses during stable long-term HD therapy and increases mortality risk. HF becomes highly prevalent but only HF with decreased LVEF < 50% is associated with increased risk of mortality.

Liver Steatosis: Better Predictor of CKD in MAFLD Than Liver Fibrosis as Determined by Transient Elastography With Controlled Attenuation Parameter.

Background: Changing the term/concept of the non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction associated fatty liver disease (MAFLD) may broaden the pathological definition that can include chronic renal involvement, and, possibly, changes chronic kidney disease's (CKD's) epidemiological association with liver disease, because CKD is associated with metabolic disorders and almost all patients with CKD present some form of an atherogenic dyslipidemia. Our study explores the relationship between MAFLD and CKD using Transient Elastography (TE) with a Controlled Attenuated Parameter (CAP). Methods: We evaluated 335 patients with diabetes with MAFLD and with high CKD risk using TE with CAP (FibroScan®). The CKD was defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Logistic regression and stepwise multiple logistic regression were used to evaluate the factors associated with CKD. In addition, a receiver operating characteristic curve (ROC) analysis was used to assess the performance of CAP and TE in predicting CKD and its optimal threshold. Results: The prevalence of CKD in our group was 60.8%. Patients with CKD had higher mean liver stiffness measurements (LSM) and CAP values than those without CKD. We found that hepatic steatosis was a better predictor of CKD than fibrosis. Univariate regression showed that CAP values >353 dB/m were predictive of CKD; while the multivariate regression analysis (after adjustment according to sex, body mass index (BMI), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc), and fasting glucose) showed that CAP values >353 dB/m were more strongly associated with the presence of CKD compared to the LSM (fibrosis) values. Conclusion: In patients with MAFLD, CAP-assessed steatosis appears to be a better predictor of CKD compared to LSM-assessed hepatic fibrosis.

Rapid decline of kidney function in diabetic kidney disease is associated with high soluble Klotho levels.

BACKGROUND: Klotho is found in two forms: a transmembrane form and a soluble form (s-Klotho). In order to be excreted, s-Klotho, that is too large to be filtered, will probably reach the proximal convoluted tubule by a transcytosis process. The aim of our study was to show the relationship between the levels of s-Klotho and tubular injury in patients with diabetic kidney disease (DKD), using as tubular injury marker the kidney injury molecule-1 (KIM-1). METHODS: Our study included 63 DKD patients (stages 1-5, mean eGFR 65.15±32.45ml/min) with a mean age 58.13±12 years. In all patients we determined serum levels of: KIM-1 and s-Klotho using ELISA, urinary albumin/creatinine ratio (UACR) and reduction in the estimated glomerular filtration rate (eGFR) per year. RESULTS: We found a strong statistically significant correlation of s-Klotho with the rate of reduction of eGFR/year (r=0.714, p=0.0004) and with the tubular injury marker KIM-1 (r=0.758, p=0.005) and strong correlations of UACR with the rate of reduction of eGFR/year (r=0.53, p<0.01), KIM-1 (r=0.49, p<0.05) and s-Klotho (r=0.52, p<0.01). CONCLUSION: Despite previous published data, that shows a decrease of s-Klotho in chronic kidney disease, in our study the rapid annual decline of kidney function but not the level of eGFR was associated with increased s-Klotho. A possible explanation could be a more severe proximal tubule injury that could lead to a reduction of tubular excretion of s-Klotho as suggested by the correlation of s-Klotho levels with the serum levels of KIM-1.

Rapid decline of kidney function in diabetic kidney disease is associated with high soluble Klotho levels / El rápido deterioro de la función renal en la nefropatía diabética se asocia con niveles elevados de Klotho soluble

BACKGROUND: Klotho is found in two forms: a transmembrane form and a soluble form (s-Klotho). In order to be excreted, s-Klotho, that is too large to be filtered, will probably reach the proximal convoluted tubule by a transcytosis process. The aim of our study was to show the relationship between the levels of s-Klotho and tubular injury in patients with diabetic kidney disease (DKD), using as tubular injury marker the kidney injury molecule-1 (KIM-1). METHODS: Our study included 63 DKD patients (stages 1-5, mean eGFR 65.15 ± 32.45 ml/min) with a mean age 58.13 ± 12 years. In all patients we determined serum levels of: KIM-1 and s-Klotho using ELISA, urinary albumin/creatinine ratio (UACR) and reduction in the estimated glomerular filtration rate (eGFR) per year. RESULTS: We found a strong statistically significant correlation of s-Klotho with the rate of reduction of eGFR/year (r = 0.714, p = 0.0004) and with the tubular injury marker KIM-1 (r = 0.758, p = 0.005) and strong correlations of UACR with the rate of reduction of eGFR/year (r = 0.53, p < 0.01), KIM-1 (r = 0.49, p < 0.05) and s-Klotho (r = 0.52, p < 0.01). CONCLUSION: Despite previous published data, that shows a decrease of s-Klotho in chronic kidney disease, in our study the rapid annual decline of kidney function but not the level of eGFR was associated with increased s-Klotho. A possible explanation could be a more severe proximal tubule injury that could lead to a reduction of tubular excretion of s-Klotho as suggested by the correlation of s-Klotho levels with the serum levels of KIM-1

ANTECEDENTES: Klotho se encuentra en el organismo en dos formas: una forma transmembranaria y una forma soluble (s-Klotho). Para excretarse s-Klotho, que es demasiado grande para ser filtrado, llegará en el túbulo contorneado proximal por un proceso de transcitosis. El objetivo del presente estudio es indicar la relación entre el nivel de s-Klotho y lesión tubular en los pacientes con la enfermedad renal diabética (DKD), utilizando como marcador de lesión tubular renal kidney injury molecule-1 (KIM-1). MÉTODOS: Nuestro estudio incluye 63 pacientes con DKD (etapas 1-5, eGFR medio 65,15 +/− 32,45 ml/min) con una edad media de 58,13 +/− 12 años. En todos los pacientes hemos determinado el nivel sérico de: KIM-1 y s-Klotho utilizando el método ELISA, coeficiente albúmina/creatinina urinaria (UACR) y la reducción de la tasa de filtración glomerular estimada (eGFR) al año. RESULTADOS: Hemos encontrado una correlación fuerte significativa desde el punto de vista estadístico de s-Klotho con una tasa de reducción de eGFR/año (r = 0,714, p = 0,0004) y con el marcador de lesión tubular KIM-1 (r = 0,758, p = 0,005) y una fuerte correlación de UACR con una tasa de reducción de eGFR/año (r = 0,53, p < 0,01), KIM-1 (r = 0,49, p < 0,05) y s-Klotho (r = 0,52, p < 0,01). CONCLUSIONES: A pesar de los datos publicados anteriormente en la literatura, que demuestran una reducción de s-Klotho en la enfermedad crónica de riñones, en nuestro estudio, la disminución rápida anual de la función renal y no el nivel de eGFR se correlaciona con el crecimiento de s-Klotho. Una posible explicación podría ser una lesión tubular proximal más grave que podría llevar a la reducción de la excreción tubular de s-Klotho, sugerida por la correlación de s-Klotho con el nivel sérico de KIM-1