Multidrug-Resistant (MDR) Urinary Tract Infections Associated with Gut Microbiota in CoV and Non-CoV Patients in a Urological Clinic during the Pandemic: A Single Center Experience.

The aim of the study was to compare the profile of COVID-19 (CoV)-infected patients with non-COVID-19 (non-CoV) patients who presented with a multidrug-resistant urinary tract infection (MDR UTI) associated with gut microbiota, as well as analyze the risk factors for their occurrence, the types of bacteria involved, and their spectrum of sensitivity. METHODS: We conducted a case-control study on patients admitted to the urology clinic of the "Parhon" Teaching Hospital in Iasi, Romania, between March 2020 and August 2022. The study group consisted of 22 CoV patients with MDR urinary infections associated with gut microbiota. For the control group, 66 non-CoV patients who developed MDR urinary infections associated with gut microbiota were selected. Electronic medical records were analyzed to determine demographics, characteristics, and risk factors. The types of urinary tract bacteria involved in the occurrence of MDR urinary infections and their sensitivity spectrum were also analyzed. RESULTS: Patients in both groups studied were over 60 years of age, with no differences in gender, environment of origin, and rate of comorbidities. Patients in the CoV group had a higher percentage of urosepsis (54.5% versus 21.2%, p < 0.05) and more hospitalization days (9.27 versus 6.09, p < 0.05). Regarding risk factors, the two groups had similar percentages of previous urologic interventions (95.45% versus 96.97%, p > 0.05), antibiotic therapy (77.3% versus 87.9%, p > 0.05), and the presence of permanent urinary catheters (77.27% versus 84.85%, p > 0.05). Escherichia coli (31.8% versus 42.4%, p > 0.05), Klebsiella spp. (22.7% versus 34.8%, p > 0.05), and Pseudomonas aeruginosa (27.3% versus 9.1%, p > 0.05) were the most common urinary tract bacteria found in the etiology of MDR urinary infections in CoV and non-CoV patients. A high percentage of the involved MDR urinary tract bacteria were resistant to quinolones (71.4-76.2% versus 80.3-82%, p > 0.05) and cephalosporins (61.9-81% versus 63.9-83.6%, p > 0.05), both in CoV and non-CoV patients. CONCLUSIONS: Patients with urological interventions who remain on indwelling urinary catheters are at an increased risk of developing MDR urinary infections associated with gut microbiota resistant to quinolones and cephalosporins. Patients with MDR UTIs who have CoV-associated symptoms seem to have a higher rate of urosepsis and a longer hospitalization length.

The Clash of the Titans: COVID-19, Carbapenem-Resistant Enterobacterales, and First mcr-1-Mediated Colistin Resistance in Humans in Romania.

(1) Background: Antibiotic resistance and coronavirus disease-19 (COVID-19) represent a dual challenge in daily clinical practice, inducing a high burden on public health systems. Hence, we aimed to dynamically evaluate the impact of COVID-19 on patients with carbapenem-resistant Enterobacterales (CRE) urinary tract infections (UTIs), as well as the antibiotic resistance trends after the onset of the pandemic. (2) Methods: We conducted a prospective study including patients with CRE UTIs who were enrolled both pre- and during the pandemic from 2019 to 2022. We further performed a standardized and comparative clinical, paraclinical, and microbiological assessment between patients with and without COVID-19. (3) Results: A total of 87 patients with CRE UTIs were included in this study (46 pre-pandemic and 41 during the pandemic, of which 21 had associated Severe Acute Respiratory Syndrome Coronavirus-2 infection). Klebsiella pneumoniae was the main etiological agent of the UTIs, with the majority of strains (82.7%) being carbapenemase producers (mainly OXA-48 producers), while five of the 34 colistin-resistant isolates were harboring the mobile colistin resistance-1 (mcr-1) gene. COVID-19 patients presented a significantly worse outcome with higher rates of intensive care unit (ICU) admissions (66.7% for COVID patients vs. 18.2% for non-COVID patients, p < 0.001), while the fatality rates were also considerably higher among patients with concomitant viral infection (33.3% vs. 12.1%, p < 0.001). Besides COVID-19, additional risk factors associated with increased mortality were urinary catheterization, sepsis with K. pneumoniae, impaired liver and kidney function, and an inappropriate initial empiric antibiotic therapy. (4) Conclusions: COVID-19 showed a pronounced negative impact on patients with CRE UTIs, with significantly longer hospitalizations and higher ICU admissions and mortality rates.

Evaluation of low-dose glucocorticoid regimen in association with cyclophosphamide in patients with glomerulonephritis.

BACKGROUND: The treatment of most glomerulonephritides is still based on a combination of an oral corticosteroid and an alkylating agent, with favorable outcomes, but with serious side effects. The objective of this study was to reduce the cumulative corticosteroid dose in patients with high risk of corticosteroid-related adverse events by replacing daily oral corticosteroids with intravenous (iv) methylprednisolone pulses, associated with monthly pulse i.v. cyclophosphamide (according to KDIGO guidelines) in patients with glomerulonephritis. METHODS: This was a retrospective cohort study conducted at a single nephrology centre. In the course of a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5 g per day at the end of these 6 months, received a combination of corticosteroids and cyclophosphamide. Patients were divided in two groups: group 1 (23 patients)-included patients with high risk of corticosteroid-related adverse events received monthly methylprednisolone 1 g/day, 3 days and i.v. cyclophosphamide for 6 months, and group 2 (84 patients)-received oral corticosteroids (as per KDIGO recommended dose) and i.v. cyclophosphamide. The primary outcome-time to a combined end-point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission [proteinuria < 0.3 g per 24 h (urinary protein-creatinine rate < 300 mg/g [< 30 mg/mmol]]; partial remission (proteinuria > 0.3 but < 3.5 g per 24 h or a decrease in proteinuria by at least 50% from the initial value) and adverse events. RESULTS: At 6 months, there was no difference in the primary composite end-point: 8.7% patients from the group 1 and 20.2% patients from the group 2 (P = 0.199) reached this end-point. Similar data were also recorded at 12 months. Secondary end-points were also similar between treatment groups. More patients receiving oral corticosteroids experienced infections, but without statistical significance. CONCLUSION: Our data indicate that low i.v. dose corticosteroids and cyclophosphamide administered monthly in patients with high risk of corticosteroid-related adverse events and primary glomerulonephritis are equally effective, with fewer metabolic disorders and infections.

Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE), by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup). Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO): 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort). RESULTS: In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30-3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72-4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12-3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60-4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56-3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29-5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4%) Cox regression analysis. CONCLUSIONS: The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

Tissue advanced glycation end products (AGEs), measured by skin autofluorescence, predict mortality in peritoneal dialysis.

PURPOSE: The relation between tissue AGEs and mortality in end-stage renal disease (ESRD) is documented, but only in hemodialysis (HD) patients. This study aimed to measure and compare tissue AGEs levels in patients receiving either HD or peritoneal dialysis (PD) and to study the effect of these products on all-cause, cardiovascular or sepsis-related mortality. METHODS: Tissue AGEs were noninvasively assessed in 304 dialysis patients (202 on chronic HD and 102 on continuous ambulatory PD) by measuring skin autofluorescence using a validated Autofluorescence Reader (AGE Reader, DiagnOptics b.v., Groningen, The Netherlands). RESULTS: There was no difference in regard to AGEs levels between the HD (3.6 ± 0.8 AU)- and PD (3.5 ± 0.7 AU, p = 0.2)-treated patients. Diabetic patients had higher AGEs values in the HD group (3.97 ± 0.81 vs. 3.52 ± 0.77, p = 0.002), but not in the PD group (3.68 ± 0.6 vs. 3.45 ± 0.70, p = 0.26). In PD patients, increasing AGEs levels were associated with an elevated risk of all-cause mortality (a 2.09-fold increase for each increment of 1 AU in AGEs values) and sepsis (a 3.44-fold increase for each increment of 1 AU in AGEs values)-related mortality. Performing a similar analysis in diabetic patients, AGEs was associated only with sepsis-related mortality (a 3.08-fold increase for each increment of 1 AU in AGEs values). CONCLUSIONS: This is the first study that demonstrates a relationship between tissue AGEs levels and sepsis-related mortality in PD-treated or diabetic ESRD patients. Future studies are necessary to evaluate the non-cardiovascular effects of tissue AGEs in ESRD patients.

Plasma endocan levels associate with inflammation, vascular abnormalities, cardiovascular events, and survival in chronic kidney disease.

Plasma endocan levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. There are currently no data on endocan in patients with chronic kidney disease (CKD). Therefore, we measured plasma endocan in 251 patients with CKD (stage 1-5) and 60 control individuals. Plasma endocan concentrations correlated with estimated glomerular filtration rate (eGFR), different markers of inflammation (pentraxin 3 and high-sensitivity C-reactive protein), and vascular abnormalities (flow-mediated vasodilation (FMV) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed with respect to plasma endocan. Patients with CKD showed significantly increased plasma endocan (4.7 [IQR 1.9-9.4] compared with controls [IQR 1.1-1.5] ng/ml), with values progressively higher across stages of CKD. On univariate analysis, plasma endocan concentrations correlated negatively with eGFR and FMV, but positively with both markers of inflammation and CIMT. However, on multivariate analysis only high-sensitivity C-reactive protein, FMV, and CIMT remained significantly associated with plasma endocan. On Cox survival analysis, endocan levels were associated with all-cause mortality and CVE in these patients. Thus, plasma endocan increases in the presence of decreasing eGFR and influences all-cause mortality and CVE in patients with CKD independent of traditional and nontraditional risk factors.

Protein-energy wasting, as well as overweight and obesity, is a long-term risk factor for mortality in chronic hemodialysis patients.

INTRODUCTION: In patients with end-stage renal disease on chronic hemodialysis (HD), protein-energy wasting (PEW) is very common and is associated with increased morbidity and mortality. Evaluation of nutritional status should be performed regularly in all such patients, using multiple methods. In this study, we analyzed the influence of several nutritional markers on long-term (5 years) survival of HD patients in one center. This is the first study on the long-term influence of nutritional status on mortality in dialysis patients ever conducted in Romania. MATERIALS AND METHODS: We included all prevalent HD patients in our center. Those with ongoing acute illnesses and with inflammation (C-reactive protein ≥ 6.0 mg/l) were excluded. In the remaining subjects (N = 149, 82 males, mean age 55 years old), we performed the following measurements of nutritional status: estimation of dietary protein intake by normalized protein equivalent of nitrogen appearance (nPNA), subjective global assessment (SGA), body mass index (BMI), tricipital skinfold thickness, mid-arm circumference, assessment of body composition by bioelectrical impedance analysis (BIA), and pre-dialysis serum creatinine, albumin, and total cholesterol. We used receiver operating characteristic curves to determine the cutoff points for most of the variables, and we applied the Kaplan-Meier estimator and the Cox's proportional hazards model (stepwise method) to analyze the influence of these variables on survival. RESULTS: In univariate analysis, general factors including age ≥ 65 years, male gender, dialysis vintage ≥ 2 years, and the presence of diabetes and heart failure were all significant predictors of mortality. Among nutritional parameters, BMI ≥ 25 kg/m(2), SGA-B (mild PEW), nPNA < 1.15 g/kg per day, and the BIA-derived phase angle (PhA) <5.58° were also significantly associated with reduced survival. All of these factors maintained statistical significance in multivariate analysis, except for male gender and heart failure. CONCLUSION: We showed that low values of SGA, nPNA, and PhA independently predict mortality in HD patients. In conjunction with an earlier study, we demonstrated that the relative risk of death associated with these markers is highest during the first year of monitoring and it decreases in the following 4 years, although it still remains significantly increased. On the other hand, overweight and obesity were also associated with lower survival after 5 years, whereas this association was not apparent after 1 year.

Outcomes of dialytic modalities in a large incident registry cohort from Eastern Europe: the Romanian Renal Registry.

BACKGROUND: Studies comparing survival in hemodialysis (HD) or peritoneal dialysis (PD) patients reported controversial results, mainly during the first 2 years of treatment. Moreover, there is a significant geographic variation in the use of these modalities. We aimed to compare the survival of HD and PD patients using data from the Romanian Renal Registry. METHODS: In an intention-to-treat analysis using Kaplan-Meier and Cox proportional hazard (CPH) models, survival was compared between 8,252 incident HD patients and 1,000 incident PD patients treated between 2008 and 2011. The patients were followed from the dialysis initiation and stratified by modality on day 90. The time on dialysis was separated into four periods (3-12, 12-24, 24-36 and >36 months), and outcome comparisons were made. RESULTS: Mean survival time was 46.3 (44.9-47.6) months in PD group and 45.8 (45.3-46.3) months in HD group (p = 0.9, log-rank test). In the multivariate CPH models, age, diabetes-associated kidney disease (DM), primary renal disease and center size significantly influenced survival. In the first year of therapy, the mortality was higher in HD than in PD patients (HR = 1.34 (1.12-1.60), p = 0.001), while in the second and third year, HD patients survived better (HR = 0.69 (0.53-0.89), p = 0.005); HR = 0.56 (0.41-0.78), p = 0.001) and after 36 months, the survival difference was not statistically significant (HR = 0.63 (0.34-1.13), p = 0.1), respectively. CONCLUSIONS: Despite the survival advantage for PD patients during the first year and that of HD in the next 2 years of dialysis, the overall survival in HD and PD patients was similar and was influenced by age, DM and center size.

Procalcitonin: diagnostic value in systemic infections in chronic kidney disease or renal transplant patients.

PURPOSE: Although procalcitonin (PCT) has been described as a marker of infection and inflammation, it has not been extensively studied in patients with chronic kidney disease (CKD), end stage renal disease, or renal transplant. METHODS: PCT was routinely tested in 82 (56 dialyzed patients and 28 renal transplant recipients) consecutive cases with a strong clinical suspicion of infection, during a 6-month period, in a single referral unit. RESULTS: During the study period, 58/82 cases had confirmed infections as per definition. Patients with confirmed infections had higher values for PCT [median = 2.5 ng/mL, interquartile range (IR) = 0.9-5 ng/mL] than those without (median = 0.3 ng/mL, IR = 0.1-0.5 ng/mL), p < 0.001. Overall, for a cutoff value of 0.5 ng/mL, the sensitivity of the test was 93.1 % and the specificity 78.6. CONCLUSION: Our data indicate that significantly elevated PCT concentrations offer good sensitivity and specificity for the early diagnosis of systemic bacterial infection in patients with CKD.

Vascular access in chronic dialysis: a plastic surgeon's approach.

Thirty-five years after Brescia et al. (N Engl J Med 275:1089-1092, 1966) realized the first peripheral autogenous arteriovenous fistula, the "Achilles' heel" of chronic dialysis is still the absence of a good-quality permanent vascular access. The number of patients depending on hemodialysis is increasing. Until 10 years ago, in Romania, there was a need to treat isolated critical cases. Nowadays, every dialysis center needs algorithms for a standardized approach, adaptable for each case. We reviewed 171 consecutive arteriovenous fistulas (132 patients) performed in adults in identical standard conditions: use of an inflatable tourniquet during the vascular dissection, microsurgical techniques, and use of only autogenous tissues. We analyzed our results, the technical difficulties encountered, and their management in long-term follow-up. The aim of this study was to set up the basic principles of our algorithms. Our approach, based on our education as plastic surgeons involved in hand surgery and microsurgery, might present the advantage of sparing renal patients vascular capital.

Salmeterol/fluticasone combination in COPD: is together better?

Chronic obstructive pulmonary disease represents one of the chronic conditions for which many therapies have become available during the last few decades. They are aimed at reducing symptoms such as dyspnea, cough and sputum and many of them are given on inhalatory route. Among them, bronchodilators, such as; salmeterol or formoterol and inhaled steroids, such as budesonide or fluticasone have each proven their effectiveness in improving many clinical outcomes such as dyspnea, exacerbations number, lung function decline or health status. Currently combinations of these two classes are available in an attempt to make the inhalatory therapy more effective. These studies analyse the effectiveness of salmeterol/fluticasone combination from a clinical point of view and for a short period of time.

Quality of life following lung cancer surgery: what about before?

Lung cancer is the major malignancy worldwide with cigarette smoking being the main risk-factor. In lung cancer patients, quality of life is considered the strongest prognostic factor for survival irrespective of initial performance status, weight loss, stage of disease, number of metastatic sites, and type of treatment. The study evaluates the health-related quality of life of patients after surgical intervention using a generic questionnaire, the Medical Outcome Study Questionnaire Short Form, and compares this outcome with a normal healthy population, lung cancer patients, and coronary artery bypass grafting patients. Compared with healthy controls and coronary bypass patients, lung cancer patients had significantly higher impaired physical functioning scores, comparable with mean scores for anxiety and depression. However, health-related quality of life in lung cancer remains an issue which needs further assessment.

The reproducibility of the circadian BP rhythm in treated hypertensive patients with polycystic kidney disease and mild chronic renal impairment--a prospective ABPM study.

BACKGROUND: Diurnal BP rhythm is known to be abnormal (reduced BP fall with sleep) in chronic renal failure, dialysis and renal transplantation patients. In subjects with primary hypertension and with reduced diurnal BP fall with sleep there is consistent evidence of increased target-organ damage. However, the few studies that have addressed the reproducibility of diurnal rhythm in normal or hypertensive subjects have concluded that the BP fall with sleep is poorly reproducible. It is not known whether the same is true for patients with renal disease. METHODS: In 30 subjects with autosomal polycystic kidney disease (ADPKD), mild chronic renal failure and normal office BP levels on standardised anti-hypertensive treatment, ambulatory blood pressure monitoring (ABPM) was done three times over a twelve month period to assess the reproducibility of blood pressure fall with sleep. RESULTS: When comparing ABPM 2 with the ABPM 1 recording (3 months difference between measurements) only 43.3% of the patients maintained the initial dipping category (defined by quartiles of the ABPM 1 diurnal BP distribution). The same proportion of subjects had a similar dipping category, when ABPM 3 was compared to ABPM 1 (9 months difference between measurements), but a large (24%) subset of patients had dramatic shifts in their amplitude in nocturnal BP fall, significantly greater than those recorded after a shorter inter-measurement interval. Equally important, our study reveals the fact that, with time, there is no tendency to decrease circadian variation: a similar proportion (a quarter to one third) of patients increased or decreased their amplitude in nocturnal BP fall, at 3 and 9 months. When several ABPM measurements are repeated for the same patients, the repeatability is even worse, since only 36.6% of our study population maintained the initial dipping category across all three ABPM determinations (ABPM 1 and ABPM 2 and ABPM 3). CONCLUSIONS: There is a widespread abnormality in diurnal BP rhythm in ADPKD patients with renal impairment, but the extent of this abnormality varies considerably over time. It is too simplistic to assume that, having arbitrarily categorised subjects into "dippers" or "non-dippers", these labels will always be valid. Thus, it would be unwise to extrapolate the impact of a single baseline circadian BP profile on organ target end points.

[The link between glomerulonephritis and hydatid disease ]. / Relatia glomerulonefrita boala hidatica.

The presence of glomerular damage was evaluated for 338 patients, adults (298) and children (40), with pulmonary or hepatic hydatid disease. A descriptive study was used. The glomerular syndrome was present in 2 children (5%) with hydatid disease, 22 adults (11%) with liver echinococcosis and 28 adults (18%) with pulmonary echinococcosis. An early stage diagnosis and proper treatment will determine the reversibility of glomerulonephritis.