Aminopeptidasic Enzymes as Early Biomarkers of Cardiac Surgery-Associated Acute Kidney Injury and Long-Term Events.

BACKGROUND: Diagnosis of acute kidney injury (AKI) relies on serum creatinine (SCr) changes. This study investigated if urinary aminopeptidases are early and predictive biomarkers of cardiac surgery-associated AKI (CSA-AKI). METHODS: Glutamyl aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), dipeptidyl peptidase-4 (DPP4), proteinuria, albuminuria, N-acetyl-ß-D-glucosaminidase (NAG), and neutrophile gelatinase-associated lipocalin (NGAL) were measured in urine samples from 44 patients at arrival in the intensive care unit (ICU) after cardiac surgery. Sensitivity, specificity, and positive and negative predictive value for diagnosis of stages 1, 2, and 3 of AKI were analyzed for the highest quartile of each marker. We also studied the relationship with SCr after surgery, 6- and 12-month glomerular filtration rates (GFRs), and other long-term events over the next 5 years. RESULTS: GluAp diagnosed the maximal number of patients that developed stage 2 or 3 of AKI, increasing diagnostic sensitivity from 0% to 75%. In addition, GluAp and DPP4 were related to the decrease in GFR at 6 or 12 months after surgery. CONCLUSIONS: Urinary aminopeptidases are a potential tool for the early diagnosis of CSA-AKI, with GluAp being the most effective marker for diagnosing stage 2 or 3 of AKI at ICU admission. GluAp and DPP4 serve as predictive biomarkers for a decrease in GFR.

Underwater Endoscopic Mucosal Resection Vs Conventional Endoscopic Mucosal Resection for Superficial Nonampullary Duodenal Epithelial Tumors in the Western Setting.

BACKGROUND & AIMS: Conventional endoscopic mucosal resection (C-EMR) is established as the primary treatment modality for superficial nonampullary duodenal epithelial tumors (SNADETs), but recently underwater endoscopic mucosal resection (U-EMR) has emerged as a potential alternative. The majority of previous studies focused on Asian populations and small lesions (≤20 mm). We aimed to compare the efficacy and outcomes of U-EMR vs C-EMR for SNADETs in a Western setting. METHODS: This was a retrospective multinational study from 10 European centers that performed both C-EMR and U-EMR between January 2013 and July 2023. The main outcomes were the technical success, procedure-related adverse events (AEs), and the residual/recurrent adenoma (RRA) rate, evaluated on a per-lesion basis. We assessed the association between the type of endoscopic mucosal resection and the occurrence of AEs or RRAs using mixed-effects logistic regression models (propensity scores). Sensitivity analyses were performed for lesions ≤20 mm or >20 mm. RESULTS: A total of 290 SNADETs submitted to endoscopic resection during the study period met the inclusion criteria and were analyzed (C-EMR: n = 201, 69.3%; U-EMR: n = 89, 30.7%). The overall technical success rate was 95.5% and comparable between groups. In logistic regression models, compared with U-EMR, C-EMR was associated with a significantly higher frequency of overall delayed AEs (odds ratio [OR], 4.95; 95% CI, 2.87-8.53), postprocedural bleeding (OR, 7.92; 95% CI, 3.95-15.89), and RRAs (OR, 3.66; 95% CI, 2.49-5.37). Sensitivity analyses confirmed these results when solely considering either small (≤20 mm) or large (>20 mm) lesions. CONCLUSIONS: Compared with C-EMR, U-EMR was associated with a lower rate of overall AEs and RRAs, regardless of lesion size. Our results confirm the possible role of U-EMR as an effective and safe technique in the management of SNADETs.

Incidence of hypophosphataemia after ICU admission in mechanically ventilated patients and its relationship with risk factors for refeeding syndrome.

OBJECTIVE: To describe the incidence of hypophosphatemia in patients admitted to the ICU who have required mechanical ventilation. To analyze the presence of risk factors and its relationship with nutritional practice. DESIGN: Prospective observational study. SETTING: Polyvalent ICUs of 2 University Hospitals. PATIENTS OR PARTICIPANTS: Patients on invasive mechanical ventilation ≥72 h with normal level of phosphorus at admission. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Electrolyte levels (phosphorus, magnesium, potassium) were determined on admission to the ICU and at 96 h. Risk categories on admission, caloric intake, insulin doses and acid-base status during the first 4 days of admission were recorded. Incidence was calculated as the number of patients who developed hypophosphataemia after admission. Univariate analysis was performed for between-group comparison and multivariate analysis of potential risk factors. RESULTS: 89 patients were included. The incidence of hypophosphataemia was 32.6%. In these patients phosphorus decreased from 3.57 ±â€¯1.02 mmol/l to 1.87 ±â€¯0.65 mmol/l (52.3%). The mean kcal/kg/24 h provided in the first 4 days was 17.4 ±â€¯4.1, with no difference between the group that developed hypophosphataemia and the group that did not. Significant risk factors were insulin doses administered and pH and PaCO2 values. CONCLUSIONS: The incidence of hypophosphataemia at 96 h from admission in mechanically ventilated patients is high and unrelated to the risk category and hypocaloric nutritional practice used. Insulin dosis and acid-base status are the main determinants of its occurrence.

Evaluation of Intranasal Midazolam for Pediatric Sedation during the Suturing of Traumatic Lacerations: A Systematic Review.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of intranasal midazolam as part of a paediatric sedation and analgesic procedure during the suturing of traumatic lacerations in paediatric emergency departments. METHODOLOGY: A systematic review of clinical trials was completed in July 2021. The databases consulted were PUBMED, SCOPUS, WEB OF SCIENCE, NICE and Virtual Health Library. ELIGIBILITY CRITERIA: randomised and nonrandomised clinical trials. Two independent, blinded reviewers performed the selection and data extraction. The participants were 746 children, of whom, 377 received intranasal midazolam. All of the children were admitted to an emergency department for traumatic lacerations that required suturing. The quality of the articles was evaluated with the Jadad scale. This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: Nine studies were included in the review. The intranasal administration of midazolam in healthy children produces anxiolysis and minimal/moderate sedation without serious side effects. Although there are combinations of parenteral drugs that produce deeper sedation, they also have greater adverse effects. No significant differences in the initiation of sedation and the suture procedure were found between the intranasal route and the parenteral route. CONCLUSIONS: The use of intranasal midazolam in healthy children produces sufficiently intense and long-lasting sedation to allow for the suturing of traumatic lacerations that do not present other complications; therefore, this drug can be used effectively in paediatric emergency departments.

Comparison of two repositioning schedules for the prevention of pressure ulcers in patients on mechanical ventilation with alternating pressure air mattresses.

PURPOSE: The objective was to compare the effectiveness of repositioning every 2 or 4 h for preventing pressure ulcer development in patients in intensive care unit under mechanical ventilation (MV). METHODS: This was a pragmatic, open-label randomized clinical trial in consecutive patients on an alternating pressure air mattress (APAM) requiring invasive MV for at least 24 h in a university hospital in Spain. Eligible participants were randomly assigned to groups for repositioning every 2 (n = 165) or 4 (n = 164) h. The primary outcome was the incidence of a pressure ulcer of at least grade II during ICU stay. RESULTS: A pressure ulcer of at least grade II developed in 10.3% (17/165) of patients turned every 2 h versus 13.4% (22/164) of those turned every 4 h (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.46-1.71, P = 0.73). The composite end point of device-related adverse events was recorded in 47.9 versus 36.6% (HR 1.50, CI 95% 1.06-2.11, P = 0.02), unplanned extubation in 11.5 versus 6.7% (HR 1.77, 95% CI 0.84-3.75, P = 0. 13), and endotracheal tube obstruction in 36.4 versus 30.5%, respectively (HR 1.44, 95% CI 0.98-2.12, P = 0.065). The median (interquartile range) daily nursing workload for manual repositioning was 21 (14-27) versus 11 min/patient (8-15) (P < 0.001). CONCLUSIONS: A strategy aimed at increasing repositioning frequency (2 versus 4 h) in patients under MV and on an APAM did not reduce the incidence of pressure ulcers. However, it did increase device-related adverse events and daily nursing workload.

Hospital-acquired pressure ulcers and risk of hospital mortality in intensive care patients on mechanical ventilation.

RATIONALE, AIMS AND OBJECTIVES: Pressure ulcers (PUs) are a common and serious complication in critically ill patients. The aim of this study was to evaluate the relationship between the development of a PU and hospital mortality in patients requiring mechanical ventilation (MV) in an intensive care unit (ICU). METHODS: A prospective cohort study was performed over two years in patients requiring MV for ≥ 24 hours in a medical-surgical ICU. Primary outcome measure was hospital mortality and main independent variable was the development of a PU grade ≥ II. Hazard ratios (HRs) were calculated using a Cox model with time-dependent covariates. RESULTS: Out of 563 patients in the study, 110 (19.5%) developed a PU. Overall hospital mortality was 48.7%. In the adjusted multivariate model, PU onset was a significant independent predictor of mortality (adjusted HR, 1.28; 95% confidence interval, 1.003-1.65; P = 0.047). The model also included the Acute Physiology and Chronic Health Evaluation II score, total Sequential Organ Failure Assessment on day 3, hepatic cirrhosis and medical admission. CONCLUSION: Within the limitations of a single-centre approach, PU development appears to be associated with an increase in mortality among patients requiring MV for 24 hours or longer.

Comparison of alternating pressure mattresses and overlays for prevention of pressure ulcers in ventilated intensive care patients: a quasi-experimental study.

AIM: To compare the effectiveness of alternating pressure air mattresses vs. overlays to prevent pressure ulcers in mechanically ventilated patients in intensive care units. BACKGROUND: Pressure ulcers prevention is an important issue in the nursing of critically ill patients. It is not clear whether alternating pressure air mattresses are more effective than overlays to prevent pressure ulcers. DESIGN: Prospective quasi-experimental study. METHODS: A prospective quasi-experimental study was conducted among patients in the medical-surgery intensive care unit of a university hospital on mechanical ventilation ≥24 hours during two time periods (2001 and 2006). Overlays were used in 2001 and mattresses in 2006. Primary outcome was the incidence of pressure ulcers grade ≥II (according to the European Pressure Ulcer Advisory Panel) during intensive care unit stay. RESULTS: The study included 221 patients (116 in 2001 and 105 in 2006). Baseline characteristics were similar between groups except for a higher Acute Physiology and Chronic Health Evaluation III score, total and first-day respiratory Sequential Organ Failure Assessment Score on day 1 in overlay group. There was significantly lower incidence density in the mattress vs. overlay group (12·41 cases/1000 days vs. 18·67 cases/1000 days of stay). The multivariate analyses showed the use of the mattress to be a protective factor against pressure ulcer onset. CONCLUSION: This quasi-experiment study that alternative pressure air mattresses were more effective than alternating pressure air overlays in preventing pressure ulcers in mechanically ventilated critical care patients.

Pressure ulcer incidence and risk factors in ventilated intensive care patients.

PURPOSE: The aim of this study was to determine the incidence of pressure ulcers (PUs) in ventilated patients in all intensive care units (ICUs) in Granada (Spain) and identify risk factors for their development. MATERIALS AND METHODS: A prospective cohort study in 9 medical-surgical ICUs was conducted. Two hundred ninety-nine patients with more than 24 hours on mechanical ventilation (MV) were enrolled during 2 periods in a 5-month study. Pressure ulcers of patients were measured according to the European Pressure Ulcer Advisory Panel. RESULTS: Of the 299 patients initially enrolled, 47 (16%) developed PUs of at least grade II severity. The incidence density of PUs was 13.4 cases per 1000 patient-days of ICU stay and 19.6 cases per 1000 patient-days on MV. Logistic regression identified first-day respiratory sequential organ failure assessment (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.026-2.360; P = .037), fourth-day cardiovascular sequential organ failure assessment (OR, 1.33; 95% CI, 1.066-1.664; P = .012), age (OR, 1.042; 95% CI, 1.013-1.072; P = .004), winter period (OR, 4.60; 95% CI, 1.99-10.59; P < .001), and length of MV before PUs (OR, 1.042; 95% CI, 1.005-1.080; P = .024) as significant independent predictors of PU development. CONCLUSIONS: Among other factors previously known in ventilated patients, duration of MV and winter period were identified as risk factors for PUs.

Positive-end expiratory pressure reduces incidence of ventilator-associated pneumonia in nonhypoxemic patients.

OBJECTIVE: To analyze the effect on clinical outcomes of prophylactic positive end expiratory pressure in nonhypoxemic ventilated patients. DESIGN: Multicenter randomized controlled clinical trial. SETTING: One trauma and two general intensive care units in two university hospitals. PATIENTS: One hundred thirty-one mechanically ventilated patients with normal chest radiograph and PaO2/FiO2 above 250. INTERVENTIONS: Patients were randomly allocated to receive mechanical ventilation with 5-8 cm H2O of positive end-expiratory pressure (PEEP) (PEEP group, n = 66) or no-PEEP (control group, n = 65). MEASUREMENTS AND MAIN RESULTS: Primary end-point variable was hospital mortality. Secondary outcomes included microbiologically confirmed ventilator-associated pneumonia, acute respiratory distress syndrome, barotrauma, atelectasis, and hypoxemia (PaO2/FiO2 <175). Both groups were similar at randomization in demographic characteristics, intensive care unit admission diagnoses, severity of illness, and risk factors for ventilator-associated pneumonia. Hospital mortality rate was similar (p = 0.58) between PEEP (29.7%) and control (25.4%) groups. Ventilator-associated pneumonia was detected in 16 (25.4%) patients in the control group and 6 (9.4%) in the PEEP group (relative risk, 0.37; 95% confidence interval = 0.15-0.84; p = 0.017). The number of patients who developed hypoxemia was significantly higher in the control group (34 of 63 patients, 54%) than in the PEEP group (12 of 64, 19%) (p < 0.001), and the hypoxemia developed after a shorter period (median [interquartile range]) in the control group than in the PEEP group (38 [20-70] hrs vs. 77 [32-164] hrs, p < 0.001). Groups did not significantly differ in incidence of acute respiratory distress syndrome (14% in controls vs. 5% in the PEEP group, p = 0.08), barotrauma (8% vs. 2%, respectively, p = 0.12), or atelectasis (27% vs. 19%, respectively, p = 0.26). CONCLUSIONS: These findings indicate that application of prophylactic PEEP in nonhypoxemic ventilated patients reduces the number of hypoxemia episodes and the incidence of ventilator-associated pneumonia.

Toward the synthesis of thapsigargin: enantioselective synthesis of 7,11-dihydroxyguaianolides.

[reaction: see text] The enantioselective synthesis of a 7,11-dihydroxyguaianolide bearing the stereochemistry present in thapsigargin, a potent and selective inhibitor of the Ca(2+) SERCA-ATPase pumps, is described. Starting from (+)-dihydrocarvone, the synthesis presents two key steps. The first one involves the photochemical rearrangement of a gamma,delta-unsaturated ketone eudesmane into the corresponding guaiane. The second step consists of the regioselective oxidation of an unprotected tetrahydroxylated ketone to provide a dihydroxylactone with the required stereochemistry.

Incidence of acute respiratory distress syndrome and its relation to age.

PURPOSE: The incidence of acute respiratory distress syndrome (ARDS) was previously considered to be relatively low, at less than 10 cases per 100,000 inhabitants per year, but recent reports suggest a higher incidence, especially in elderly patients. The objective was to determine the incidence and mortality of ARDS in our setting, both overall and by age group. MATERIALS AND METHODS: We conducted a prospective, observational study of patients older than 14 years, admitted to the intensive care units of all hospitals in a province of southern Spain (Granada) during a 5-month period in 2001. American-European Consensus Conference criteria for ARDS were used. Patients were divided into 5 age groups, and the hospital mortality was recorded. RESULTS: During the study period, 61 Granada-residing patients developed ARDS criteria. This represents an overall incidence of 23 cases per 100,000 inhabitants per year in the province. The incidence of ARDS in the age groups of 15 to 29, 30 to 44, 45 to 59, 60 to 74, and older than 74 years was 4.6, 13.6, 21.6, 51, and 73.9 cases per 100,000 inhabitants per year, respectively. The overall hospital mortality rate was 66%. CONCLUSIONS: The incidence of ARDS is higher than reported a decade ago and is especially elevated in the elderly. The mortality remains high.

Laser flash photolysis in a O3/Cl2 mixture at 266 nm in a very low-pressure flow system.

The laser flash photolysis in a very low-pressure flow system with mass spectrometry detection technique was developed for the study of oxidation reactions of chlorofluorocarbons. In this work, we have studied the UV photolysis of O3 in the presence of Cl2 at room temperature, which presents two catalytic cycles of O3 depletion with efficiencies dependent on the partial pressures in the photoreactor. The ozone dissociation was initiated with fourth harmonic pulses of a Nd:YAG laser. The detection of the reactants and the final and intermediate reaction products was performed with real-time mass spectrometry. The variations of the O3, Cl2 and ClO concentration were measured. The equations system associated to a proposed kinetic scheme was solved numerically and excellent agreement with the experimental results was obtained. The results from this work allowed the determination of the wall loss rates of the O(1D), Cl and ClO radicals.

Quantification of lung water by transpulmonary thermodilution in normal and edematous lung.

PURPOSE: To analyze the accuracy of the transpulmonary thermodilution method in the determination of extravascular lung water (EVLW). MATERIAL AND METHODS: Acute lung injury was produced in eight adolescent pigs weighing 28 to 35 kg by bronchoalveolar lung lavage. EVLW was measured by transpulmonary thermodilution method before and after the intratracheal introduction of 250 or 500 mL of saline solution in different lung injury conditions. No corrections for anatomic dead space were made. RESULTS: When 250 mL was introduced, 195 +/- 17 mL was detected in normal (uninjured) lungs versus 74 +/- 57 mL in edematous (injured) lungs (P <.05). When 500 mL was introduced, 343 +/- 67 mL was detected in normal lungs versus 160 +/- 51 mL in edematous lungs (P <.001). Considering all determinations together, there was a very high negative correlation between the baseline EVLW and the percentage of EVLW detected (r = -0.92, P <.001). CONCLUSION: The transpulmonary thermodilution method is very accurate to detect changes in EVLW in normal lungs. In edematous lung, this method may underestimate the EVLW.

Valoración de la eficacia de clorpropamida mediante determinación de glucohemoglobina / Evaluation of the efficacy of chlorpropamide by glucohemoglobin determination

Durante tres meses se estudió a 22 pacientes diabéticos cuya edad fluctuaba entre 26 y 68 años, a los que se administró clorpropamida utilizando un método para valorar el grado de control alcanzado durante el tratamiento, así como la glucemia en ayunas (que al início fue de 256 mg% y disminuyó a 123.7 mg %), la glucosuria de 24 horas (promedio inicial, 21.7 g/l; final, l.7 g/l) y la hemoglobina glucosilada (que bajó de 12.3% a 9.8%). Los datos obtenidos permiten confirmar la bondad terapéutica de clorpropamida y la utilidad de la hemoglobina glucosilada para valorar el grado de control de pacientes diabéticos