A deep-learning model to continuously predict severe acute kidney injury based on urine output changes in critically ill patients

BACKGROUND: Acute Kidney Injury (AKI), a frequentcomplication of pateints in theIntensive Care Unit (ICU), is associated with a high mortality rate. Early prediction of AKI is essential in order to trigger the use of preventive careactions.METHODS: The aim of this study was to ascertain the accuracy of two mathematical analysis models in obtaining a predictive score for AKI development. A deep learning model based on a urine output trends was compared with a logistic regression analysis for AKI prediction in stages 2 and 3 (defined as the simultaneous increase of serum creatinine and decrease of urine output, according to the Acute Kidney Injury Network (AKIN) guidelines). Two retrospective datasets including 35,573 ICU patients were analyzed. Urine output data were used to train and test the logistic regression and the deep learning model.RESULTS: The deep learning model definedan area under the curve (AUC) of 0.89 (±0.01), sensitivity=0.8 and specificity=0.84, which was higher than the logistic regression analysis. The deep learning model was able to predict 88% of AKI cases more than 12h before their onset: for every 6 patients identified as being at risk of AKI by the deep learning model, 5 experienced the event. On the contrary, for every 12 patients not considered to be at risk by the model, 2 developed AKI.CONCLUSION: In conclusion, by using urine output trends, deep learning analysis was able to predict AKI episodes more than 12h in advance, and with a higher accuracy than the classical urine output thresholds. We suggest that this algorithm could be integrated inthe ICU setting to better manage, and potentially prevent, AKI episodes

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review

Background Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. Methods For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. Results We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m2 in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. Conclusions The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study result

Correction: Etelcalcetide in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism. Multicenter Study in “Real Life”. J. Clin. Med. 2019, 8, 1066

The authors wish to make the following corrections to the previous publication [...

Ambulatory COVID-19 Patients Treated with Lactoferrin as a Supplementary Antiviral Agent: A Preliminary Study

SARS-CoV-2, an enveloped, single-stranded RNA virus causing COVID-19, exerts morbidity and mortality especially in elderly, obese individuals and those suffering from chronic conditions. In addition to the availability of vaccines and the limited efficacy of the first dose of vaccine against SARS-CoV-2 variants, there is an urgent requirement for the discovery and development of supplementary antiviral agents. Lactoferrin (Lf), a pleiotropic cationic glycoprotein of innate immunity, has been proposed as a safe treatment combined with other therapies in COVID-19 patients. Here, we present a small retrospective study on asymptomatic, paucisymptomatic, and moderate symptomatic COVID-19 Lf-treated versus Lf-untreated patients. The time required to achieve SARS-CoV-2 RNA negativization in Lf-treated patients (n = 82) was significantly lower (p &lt; 0.001) compared to that observed in Lf-untreated ones (n = 39) (15 versus 24 days). A link among reduction in symptoms, age, and Lf treatment was found. The Lf antiviral activity could be explained through the interaction with SARS-CoV-2 spike, the binding with heparan sulfate proteoglycans of cells, and the anti-inflammatory activity associated with the restoration of iron homeostasis disorders, which favor viral infection/replication. Lf could be an important supplementary treatment in counteracting SARS-CoV-2 infection, as it is also safe and well-tolerated by all treated patients

Etelcalcetide in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism. Multicenter Study in “Real Life”

Abstract: Etelcalcetide is a new calcimimetic indicated for the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients. Etelcalcetide ecacy in SHPT has been ascertained only in randomized controlled trials. This multicenter study was carried out in “real world” setting that is dierent from randomized controlled trials (RCTs) to (1) evaluate the eectiveness of etelcalcetide in SHPT, (2) to assess calcium, phosphorus, alkaline phosphatase changes, (3) to register gastrointestinal side eects. Data were collected from twenty-three dialysis units with n = 1190 patients on the charge. From this cohort, n = 168 (14%) patients were on treatment with etelcalcetide, and they were evaluated for statistics. A median weekly dose of etelcalcetide was 15 mg (7.5–45 mg). Patients were either naïve (33%) or switched from cinacalcet to obtain better control of SHPT with reduced side eects or pills burden. Serum parathyroid hormone (PTH) declined over time from a median value of 636 pg/mL to 357 pg/mL. The median time for responders (intact PTH (iPTH) range: two to nine times the upper normal limit) was 53 days; the percentage of responders increased (from baseline 27% to 63%) being similar in switched-patients and naïve-patients. Few patients had symptomatic hypocalcemia requiring etelcalcetide withdrawal (four cases (3%) at 30-day control, two cases (2%) at 60-day, one case (1%) at 90-day control). Side eects with etelcalcetide were lower (3–4%) than that registered during cinacalcet treatment (53%). Etelcalcetide is a new therapeutic option for SHPT with low side eects and pills burden. Etelcalcetide may improve adherence to therapy, avoiding unremitting SHP. It remains to be assessed whether etelcalcetide may reduce parathyroidectomy, vascular calcification, or mortality. Being etelcalcetide very potent in suppressing PTH levels, even in severe SHPT, future studies should evaluate the potential risk of more adynamic bone disease during long-term therapy

Home Pulse Pressure Predicts Death and Cardiovascular Events in Peritoneal Dialysis Patients

Increased arterial hypertension represents a prevalent condition in peritoneal dialysis patients that is often related to volume expansion. Pulse pressure is a robust predictor of mortality in dialysis patients, but its association with mortality is unknown in peritoneal patients. We investigated the relationship between home pulse pressure and survival in 140 PD patients. During a mean follow-up of 35 months, 62 patients died, and 66 experienced the combined event death/CV events. In a crude COX regression analysis, a five-unit increase in HPP was associated with a 17% increase in the hazard ratio of mortality (HR: 1.17, 95% CI 1.08–1.26 p p = 0.001). Similar results were obtained considering the combined event death–CV events as an outcome. Home pulse pressure represents, in part, arterial stiffness, and it is strongly related to all-cause mortality in peritoneal patients. In these high cardiovascular risk populations, it is important to maintain optimal blood pressure control, but it is fundamental to consider all the other cardiovascular risk indicators, such as pulse pressure. Home pulse pressure measurement is easy and feasible and can add important information for the identification and management of high-risk patients

Oxidized LDL, Gamma-Glutamyltransferase and Adverse Outcomes in Older Adults

OBJECTIVES: Gamma-glutamyltransferase (GGT) is a biomarker of liver disease and oxidative stress which was associated with all-cause and cardiovascular (CV) mortality in the general population and in patients with high risk conditions. This study aims at assessing whether oxLDL modifies the relationship between GGT, all-cause, and CV mortality in elderly individuals from the general population. DESIGN: Observational longitudinal study. SETTING: Population-based cohort of older individuals (>65 years) free of liver disease. PARTICIPANTS: One thousand and thirty-eight individuals from the Invecchiare in Chianti (InCHIANTI) study. MEASUREMENTS: Serum GGT level, oxidized low-density lipoprotein (oxLDL), CV comorbidities, all-cause and CV mortality. RESULTS: The median age of the study population (n = 1,038) was 74 years (inter-quartile range: 69-79), 152 individuals (15%) had past CV events. During a median follow-up of 9 years, 401 individuals died, 168 of them (42%) for CV causes. In adjusted analyses, GGT predicted all-cause mortality (HR for 20 U/L increase in serum GGT: 1.11, 95% CI: 1.02-1.21, P = .02) and CV mortality (HR: 1.17, 95% CI: 1.03-1.33; P = .02). Furthermore, in an analysis for interaction circulating oxLDL amplified the effect of GGT on all-cause mortality (P = .003). CONCLUSION: Circulating oxLDL amplifies the effect of GGT on mortality in the elderly. The mechanism for this association remains unknown and requires further research, including studying the potential role of GGT in oxidative stress. These results are consistent with the hypothesis of a causal role of GGT in the CV morbidity and mortality in older individuals and indicate that oxLDL plays a crucial role in the interpretation of the link between GGT and the risk of adverse clinical events in this population