Influence of patients' clinical features at intensive care unit admission on performance of cell cycle arrest biomarkers in predicting acute kidney injury.

Objectives: Identification of acute kidney injury (AKI) can be challenging in patients with a variety of clinical features at intensive care unit (ICU) admission, and the capacity of biomarkers in this subpopulation has been poorly studied. In our study we examined the influence that patients' clinical features at ICU admission have over the predicting ability of the combination of urinary tissue inhibitor of metalloproteinase-2 (TIMP2) and insulin-like growth factor binding protein 7 (IGFBP7). Methods: Urinary [TIMP2]•[IGFBP7] were measured for all patients upon admission to ICU. We calculated the receiver operating characteristics (ROC) curves for AKI prediction in the overall cohort and for subgroups of patients according to etiology of ICU admission, which included: sepsis, trauma, neurological conditions, cardiovascular diseases, respiratory diseases, and non-classifiable causes. Results: In the overall cohort of 719 patients, 239 (33.2%) developed AKI in the first seven days. [TIMP2]•[IGFBP7] at ICU admission were significantly higher in AKI patients than in non-AKI patients. This is true not only for the overall cohort but also in the other subgroups. The area under the ROC curve (AUC) for [TIMP2]•[IGFBP7] in predicting AKI in the first seven days was 0.633 (95% CI 0.588-0.678), for the overall cohort, with sensitivity and specificity of 66.1 and 51.9% respectively. When we considered patients with combined sepsis, trauma, and respiratory disease we found a higher AUC than patients without these conditions (0.711 vs. 0.575; p=0.002). Conclusions: The accuracy of [TIMP2]•[IGFBP7] in predicting the risk of AKI in the first seven days after ICU admission has significant variability when the reason for ICU admission is considered.

Laryngeal Mask Airway Supreme vs. the Spritztube tracheal cannula in anaesthetised adult patients: A randomised controlled trial.

BACKGROUND: The Spritztube is a new supraglottic airway device combining the ability to allow extraglottic ventilation of the lungs with the opportunity to perform fibreoptic-assisted intubation. OBJECTIVES: To compare the Spritztube tracheal cannula with the Laryngeal Mask Airway Supreme (LMA-S) in anaesthetised adult patients. DESIGN: A single-centre, randomised controlled study. SETTING: Tertiary hospital. PATIENTS: Mechanically ventilated patients undergoing elective surgery in the supine position under general anaesthesia were included. Main exclusion criteria were a history of, or predicted, difficult airway management according to SIAARTI guidelines and absence of written informed consent. INTERVENTIONS: Patients received the LMA-S or Spritztube tracheal cannula to facilitate ventilation of the lungs. MAIN OUTCOME MEASURES: Successful placement (primary outcome), time required for insertion, number of attempts, subjective assessment of ease of insertion, safety and incidence of complications were recorded. RESULTS: One hundred and sixty seven patients were allocated to the LMA-S or Spritztube group, respectively, a total of 334 patients. In the LMA-S group, the device insertion failed in nine patients, compared with none in the Spritztube group (P = 0.002). Spritztube insertion was easy in 100% of cases compared with 94.6% of the cases in the LMA-S group (P = 0.03). The number of attempts was significantly higher with the LMA-S compared with the Spritztube (P = 0.0007), whereas the insertion times were comparable (P = 0.06). Except for the incidence of blood-staining, which was higher in the LMA-S group (P = 0.01), the number of complications was comparable in the two groups. CONCLUSION: The Spritztube was as effective as the LMA-S in maintaining the airway with all patients being successfully ventilated without difficulty. The success rate of achieving a patent airway was comparable between the groups, with a similar occurrence of complications. TRIAL REGISTRATION: NCT03443219.

Predicting Acute Kidney Injury in Intensive Care Unit Patients: The Role of Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor-Binding Protein-7 Biomarkers.

BACKGROUND: Acute kidney injury (AKI) diagnosis is based on a rise in serum creatinine and/or fall in urine output. It has been shown that there are patients that fulfill AKI definition but do not have AKI, and there are also patients with evidence of renal injury who do not meet any criteria for AKI. Recently the innovative and emerging proteomic technology has enabled the identification of novel biomarkers that allow improved risk stratification. METHODS: Tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7) were measured to a cohort of 719 consecutive patients admitted to Intensive Care Unit (ICU). The primary endpoint was the evaluation of clinical performances of the biomarkers focusing on the probability do develop AKI in the first 7 days. RESULTS: The Kaplan-Meier analysis considering the first 7 days of ICU stay suggested a lower risk of developing AKI (p < 0.0001) for patients with a negative (<0.3; TIMP-2*IGFBP7) test. CONCLUSION: (TIMP-2*IGFBP7) at ICU admission has a good performance in predicting AKI, especially in the first 4 days in ICU.

Impact of hyperhydration on the mortality risk in critically ill patients admitted in intensive care units: comparison between bioelectrical impedance vector analysis and cumulative fluid balance recording.

BACKGROUND: Studies have demonstrated a positive correlation between fluid overload (FO) and adverse outcomes in critically ill patients. The present study aims at defining the impact of hyperhydration on the Intensive Care Unit (ICU) mortality risk, comparing Bioelectrical Impedance Vector Analysis (BIVA) assessment with cumulative fluid balance (CFB) recording. METHODS: We performed a prospective, dual-centre, clinician-blinded, observational study of consecutive patients admitted to ICU with an expected length of ICU stay of at least 72 hours. During observational period (72-120 hours), CFB was recorded and cumulative FO was calculated. At the admission and daily during the observational period, BIVA was performed. We considered FO between 5% and 9.99% as moderate and a FO ≥ 10% as severe. According to BIVA hydration scale of lean body mass, patients were classified as normohydrated (>72.7%-74.3%), mild (>71%-72.7%), moderate (>69%-71%) and severe (≤ 69%) dehydrated and mild (>74.3%-81%), moderate (>81%-87%) and severe (>87%) hyperhydrated. Two multivariate logistic regression models were performed: the ICU mortality was the response variable, while the predictor variables were hyperhydration, measured by BIVA (BIVA model), and FO (FO model). A p-value <0.05 was considered to indicate statistical significance. RESULTS: One hundred and twenty-five patients were enrolled (mean age 64.8 ± 16.0 years, 65.6% male). Five hundred and fifteen BIVA measurements were performed. The mean CFB recorded at the end of the observational period was 2.7 ± 4.1 L, while the maximum hydration of lean body mass estimated by BIVA was 83.67 ± 6.39%. Severe hyperhydration measured by BIVA was the only variable found to be significantly associated with ICU mortality (OR 22.91; 95% CI 2.38-220.07; p < 0.01). CONCLUSIONS: The hydration status measured by BIVA seems to predict mortality risk in ICU patients better than the conventional method of fluid balance recording. Moreover, it appears to be safe, easy to use and adequate for bedside evaluation. Randomized clinical trials with an adequate sample size are needed to validate the diagnostic properties of BIVA in the goal-directed fluid management of critically ill patients in ICU.

[The validation of C-POT (Critical-Care Pain Observation Tool) scale: a tool for assessing pain in intensive care patients]. / La validazione della scala C-POT: uno strumento di rilevazione del dolore nei pazienti in terapia intensiva.

UNLABELLED: Pain in intensive care units is a frequent and often undermanaged problem, mainly because appropriate pain assessment tools for non communicative patients are still missing. The Critical-Care Pain Observation Tool (C-POT) is currently considered one of the best scales, both for psychometric properties and clinical feasibility. AIM: To preliminarily analyze the reliability and validity of the C-POT in a hospital setting, and its clinical feasibility. METHODS: 50 nursing staff members from three different critical care settings of Vicenza Hospital administered the C-POT to 121 in patients, at rest and after usual nursing care activities. In addition, NOPPAIN forms were completed during care activities and communicative patients were asked to rate their pain using numerical rating scale 0-10. Reliability, with Cronbach's alfa and inter-rater agreement (Spearman's non parametric rank correlation), as well as criterion, concurrent and discriminant validity were determined. RESULTS: A good internal consistency and good levels of agreement between independent raters were observed (ρSpearman 0.55 at rest and 0.66 during activity). Moderate correlations between C-POT and numerical rating scale 0-10, and between C-POT and NOPPAIN were found. Moreover, C-POT scores varied from rest to activities, and from non painful to painful procedures. DISCUSSION: C-POT showed good psychometric properties in terms of reliability and validity; these results, added to positive nurses evaluations, support its utility and use in the clinical setting.

The Use of Endoclips in Thoracoscopic Correction of Esophageal Atresia: Advantages or Complications?

Background: Thoracoscopic correction of esophageal atresia (EA) with tracheoesophageal fistula (TEF) has been increasingly widespread, but is still one of the most advanced pediatric surgical skills. This procedure has a challenging learning curve, and usually initially requires a longer operative time than the open approach; furthermore to perform this intervention, the surgeon must be very experienced in endocorporeal knotting. In our opinion, standardization of the technique and the application of "tricks" (including the use of titanium endoclips for TEF closure) to make surgical steps easier, faster, and safe would be useful to the surgeon and to the patient above all. Materials and Methods: We present our experience in thoracoscopic treatment of EA/TEF over the past 12 years; during this period, we have treated 32 neonates. We reviewed all patient clinical records evaluating demographics, surgical technique, postoperative period, and long-term follow-up. Results: Thirty-one patients were affected by type C EA (five presented with a long-gap defect); one by type E EA. Mean gestational age was 36 + 5 weeks (29-41). Mean weight at surgery was 2340 g (990-3715 g). Through a transpleural thoracoscopic approach, after Azygos vein division, TEF was closed by sutures (silk/polydioxanone [PDS]) in 4 patients while in the remaining 28 two 5 mm titanium endoclips were applied. Esophageal anastomosis was then performed with 8-12 interrupted 5/0 absorbable sutures. We had two intraoperative complications in endoclips application (migration and misplacement), which were immediately resolved. After a contrast study on sixth to seventh postoperative day (average eighth), in the absence of leakage, oral feeding was started and chest tube removed. Four to six weeks after surgery, patients underwent endoscopic evaluation. At a follow-up of 9 years, we had no postoperative complications due to endoclips: neither TEF recurrence, nor problems due to clips dislocation. Conclusions: Although the benefits of thoracoscopic correction of EA/TEF are still discussed, we agree with this part of recent literature that considers thoracoscopic approach as a feasible, safe, and advantageous alternative to the traditional open approach. We also want to emphasize that in our experience, TEF closure by titanium endoclips is fast, reducing operative time, and effective, with no reported long-term complications in our case series. Overall success rate after clips application is, in our series, 100%. The only limit we have found, above all for low-weight patients, is the diameter of the clip applier which needs a 5 mm access even if the surgeon uses 3 mm operative instruments.

Routine Adoption of Urinary [IGFBP7]∙[TIMP-2] to Assess Acute Kidney Injury at Any Stage 12 hours After Intensive Care Unit Admission: a Prospective Cohort Study.

The urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]∙[IGFBP7]) have been introduced to improve risk prediction of severe acute kidney injury (AKI) within 12 hours of measurement. We performed a prospective cohort study to evaluate if the predictive value of [TIMP-2]∙[IGFBP7] for AKI might continue after 12 hours. We enrolled 442 critically ill adult patients from June to December 2016. Urine samples were collected at admission for [TIMP-2]∙[IGFBP7] measurement. Baseline patient characteristics were recorded including patients' demographics, prior health history, and the main reason for admission to build a logistic regression model to predict AKI. AKI occurrence differed between patients with [TIMP-2]∙[IGFBP7] ≤0.3 and >0.3 (ng/ml)2/1000 (31.9% and 68.10% respectively; p < 0.001). Patients with AKI had higher biomarker values compared to those without AKI (0.66 (0.21-2.84) vs 0.22 (0.08-0.63) (ng/ml)2/1000; p < 0.001). [TIMP-2]∙[IGFBP7] at ICU admission had a lower performance in predicting AKI at any stage within 48 hours and 7 days after measurement (area under the receiver operating characteristic curve (AUC) equal to 0.70 (95%CI 0.65-0.76), AUC 0.68 (95%CI 0.63-0.73)). In the logistic regression model, 0.1 (ng/ml)2/1000-unit increment was likely to increase the risk of AKI by 2% (p = 0.002).

Development and validation of quick Acute Kidney Injury-score (q-AKI) to predict acute kidney injury at admission to a multidisciplinary intensive care unit.

AKI is associated with increased risk of death, prolonged length of stay and development of de-novo chronic kidney disease. The aim of our study is the development and validation of prediction models to identify the risk of AKI in ICU patients up to 7 days. We retrospectively recruited 692 consecutive patients admitted to the ICU at San Bortolo Hospital (Vicenza, Italy) from 1 June 2016 to 31 March 2017: 455 patients were treated as the derivation group and 237 as the validation group. Candidate variables were selected based on a literature review and expert opinion. Admission eGFR< 90 ml/min /1.73 mq (OR 2.78; 95% CI 1.78-4.35; p<0.001); SOFAcv ≥ 2 (OR 2.23; 95% CI 1.48-3.37; p<0.001); lactate ≥ 2 mmol/L (OR 1.81; 95% CI 1.19-2.74; p = 0.005) and (TIMP-2)•(IGFBP7) ≥ 0.3 (OR 1.65; 95% CI 1.08-2.52; p = 0.019) were significantly associated with AKI. For the q-AKI score, we stratified patients into different AKI Risk score levels: 0-2; 3-4; 5-6; 7-8 and 9-10. In both cohorts, we observed that the proportion of AKI patients was higher in the higher score levels.

Airway management with Fastrach laryngeal mask versus Spritztube: a prospective randomized manikin-based study.

BACKGROUND: A new promising device, the Spritztube (ST), was developed combining the ability to perform both supraglottic ventilation and orotracheal fibreoptic intubation using the same device, allowing an easy passage from supraglottic ventilation to tracheal ventilation avoiding apnea. The present study aims to compare the speed and the subjective ease of insertion of the novel tracheal tube (Spritztube®) compared to the intubating laryngeal mask airway Fastrach™ (FT-LMA) in a simulation environment. METHODS: Each participant received verbal instruction and practical demonstration concerning "technique of insertion" for both devices on manikin and, in a randomized order, used both devices. Time of placement (T1), time of inflation (T2), the elapsed procedural time (T3), ease of insertion, time of exchange maneuver for intubation (T4), success rates and number of attempts were recorded for each EAD. RESULTS: Forty-seven participants were enrolled. The ST was judged as easier insertion than FT-LMA (P<0.001) having also a significant higher success rate than FT-LMA (P<0.001). Number of attempts for insertion was similar. Number of attempts for exchange to ETI was significantly more for FT-LMA (P<0.001). FT-LMA was applied 11 s faster than the ST (median T3 Fastrach: 13 s, ST: 24 s, P<0.001) as the exchange maneuver for ETI (median T4 FT-LMA: 13 s, ST: 24 s, P<0.001). CONCLUSIONS: In a manikin simulation setting, insertion and intubation with and ST was performed 11 s slower than with use of a FT-LMA.

Development of the New Kibou® Equipment for Continuous Renal Replacement Therapy from Scratch to the Final Configuration.

A new technology has recently appeared in the area of extracorporeal therapies for critically ill patients with acute kidney injury. The International Renal Research Institute of Vicenza was involved from the beginning in the development of a new continuous renal replacement therapy (CRRT) equipment with peculiar characteristics. We report the overall experience from design of the new machine to its in vitro and in vivo testing. Kibou® (Asahi Kasei Kuraray Medical Co., Ltd., Tokyo, Japan) is a new multifunctional machine designed for delivering RRT. Kibou® carries out many features of the fourth generation CRRT machines including the possibility of a dynamic prescription and reduction of nursing workload. We describe our first experience with this new device, focusing on several usability and performance parameters. A specific in vitro protocol was designed to analyze the various characteristics and accuracy of performance of the machine. Furthermore, a preliminary in vivo alpha trial with 12 CRRT sessions was performed to test, characterize and evaluate the machine in terms of usability, flexibility and reliability. The in vitro evaluation confirmed an adequate design and a good usability of the machine with accurate delivery of prescribed parameters. No adverse events were observed during the in vivo test that confirmed usability and safety together with accuracy of treatment delivery in different modalities. In general, the machine was rated by physicians and nurses involved in the evaluation as practical and easy to use, although a specific training is required to familiarize with the equipment. A large-scale multicenter beta trial is required to confirm the results reported in this preliminary evaluation in terms of safety, accuracy and performance of Kibou®.

Routine adoption of TIMP2 and IGFBP7 biomarkers in cardiac surgery for early identification of acute kidney injury.

BACKGROUND AND PURPOSE: Acute Kidney Injury (AKI) is a severe complication affecting many hospitalized patients after cardiac surgery, with negative impacts on short- and long-term clinical outcomes and on healthcare costs. Recently, clinical interest has been aimed at defining and classifying AKI, identifying risk factors and developing diagnostic strategies to identify patients at risk early on. Achieving an early and accurate diagnosis of AKI is a crucial issue, because prevention and timely detection may help to prevent negative clinical outcomes and avoid AKI-associated costs. In this retrospective study, we evaluate the NephroCheck Test as a diagnostic tool for early detection of AKI in a high-risk population of patients undergoing cardiac surgery at the San Bortolo Hospital of Vicenza. METHODS: We assessed the ability of the NephroCheck Test to predict the probability of developing CSA-AKI (cardiac surgery-associated AKI) and evaluated its accuracy as a diagnostic test, by building a multivariate logistic regression model for CSA-AKI prediction. RESULTS: Based on our findings, when the results of the NephroCheck Test are included in a multivariate model its performance is substantially improved, as compared to the benchmark model, which only accounts for the other clinical factors. We also define a rule - in terms of a probability cut-off - for discriminating cases that are at higher risk of developing AKI of any stage versus those in which AKI is less likely. CONCLUSIONS: Our study has implications in clinical practice: when a Nephrocheck Test result is >0.3 ng/dL, an automated electronic alert prompts the physician to intervene by following a checklist of preventive measures.

Interventional approach to reduce thromboembolic risk in patients with atrial fibrillation ineligible for oral anticoagulation.

The annual incidence of stroke in patients with nonrheumatic atrial fibrillation averages 5% per year and increases with age, left ventricular dysfunction, hypertension, diabetes or prior stroke. Since in nonrheumatic atrial fibrillation 91% of left atrial thrombi are located in the left atrial appendage, in patients ineligible for oral anticoagulation it was suggested the percutaneous closure of left atrial appendage as a therapeutic option to reduce embolic risk. In this article we report our initial experience with this procedure, which was uneventful and efficacious at short-term follow-up. In conclusion, the interventional approach in patients with atrial fibrillation ineligible for oral anticoagulation seems feasible and promising, and deserves further investigation.

Four-side near-infrared spectroscopy measured in a paediatric population during surgery for congenital heart disease.

In this study we monitored renal, hepatic and muscular oxygen saturations by near-infrared spectroscopy and we evaluated the correlation with variables that could affect tissue oxygenation in 16 paediatric patients during surgical heart procedure. We considered the following phases: 1) basal time (after induction of anaesthesia and before median sternotomy), 2) before starting cardiopulmonary bypass, 3) 15 min after starting it, 4) at half time, 5) 15 min before the end, 6) at the end, 7) 15 min after the end, and 8) 10 min before paediatric intensive care unit admission. Heart rate, mean arterial pressure, peripheral oxygen saturation, serum lactate, haemoglobin, blood gas analysis, and rectal temperature were registered. We found a decrease of all monitored regional saturations (rSO(2)) (cerebral P = 0.006, hepatic P = 0.005) before starting the bypass. After this time, cerebral saturation gradually increased without reaching the basal value; renal and liver saturations increased after starting bypass; muscular rSO(2) increased in the second half (P = 0.005). A statistically significative inverse correlation between cerebral rSO(2) and pH was observed. In conclusion, during paediatric heart surgery a vulnerable period was identified. We underline the necessity to monitor this phase.

Incidence, predictors, and outcome of conduction disorders after transcatheter self-expandable aortic valve implantation.

The aims of the present study were to investigate the incidence and characteristics of conduction disorders (CDs) after transcatheter aortic valve implantation (TAVI), to analyze the predictors of permanent pacemaker (PPM) implantation, and to evaluate the outcomes of CDs over time. In particular, we sought to investigate whether the depth of deployment and other technical aspects of valve implantation might predict the need for PPM implantation after TAVI. TAVI has been reported to favor the onset or worsening of CDs often requiring PPM implantation. A total of 70 patients with aortic stenosis due to dystrophic calcification underwent TAVI with third-generation CoreValve Revalving System from May 2007 to April 2009. We collected electrocardiograms at baseline, during TAVI, during hospitalization and at the 1-, 3-, 6-, and 12-month follow-up visits thereafter. The clinical, anatomic, and procedural variables were tested to identify the predictors of PPM implantation. The PPM dependency at follow-up was analyzed. Six patients were excluded from the analysis because of a pre-existing PPM. Of the 64 patients, 32 (50%) had one or more atrioventricular-intraventricular CDs at baseline. TAVI induced a worsening in the CDs in 49 (77%) of the 64 patients, with 25 (39%) requiring in-hospital PPM implantation. On multivariate analysis, the independent predictors of PPM implantation were the depth of the prosthesis implantation (p = 0.039) and the pre-existing right bundle branch block (p = 0.046). A trend in the recovery of the CDs over time was recorded, although 2 patients required PPM implantation 1 month after discharge for late complete atrioventricular block. In conclusion, TAVI often induces or worsens CDs, requiring PPM in more than one third of patients, although a trend in the recovery of CDs during the midterm was recorded. The independent predictors of PPM implantation were the depth of prosthesis implantation and pre-existing right bundle branch block.

Expanding the eligibility for transcatheter aortic valve implantation the trans-subclavian retrograde approach using: the III generation CoreValve revalving system.

OBJECTIVES: Our aim was to assess the safety and feasibility of the retrograde trans-subclavian approach to transcatheter aortic valve implantation (TAVI) in selected high-risk patients with aortic stenosis (AS) and severe peripheral vasculopathy. BACKGROUND: TAVI is an emerging therapeutic option to treat inoperable/high-risk patients affected by symptomatic AS. However, these patients are also often affected by severe iliac-femoral arteriopathy, rendering the transfemoral approach unemployable for percutaneous revalving procedure. METHODS: From among those patients in our department between May 2007 and December 2008, who were refused surgical aortic valve replacement because of high surgical risk and were ineligible for transfemoral percutaneous aortic valve replacement, we scheduled 3 for TAVI by the subclavian approach. Procedures were performed by a combined team of cardiologists, cardiac surgeons, and anesthetists in the catheterization laboratory. The III generation CoreValve Revalving System (CoreValve Inc., Irvine, California) with an 18-F delivery system was introduced in all cases by the left subclavian artery. RESULTS: Prosthetic valves were successfully implanted in all 3 cases, leading to a fall in transvalvular gradient without significant paravalvular regurgitation. No intraprocedural or periprocedural complications occurred. Two patients developed an atrioventricular block requiring the implantation of a permanent pacemaker. All patients were discharged in asymptomatic status, with good prosthesis performance. No adverse events occurred within the 3-month follow-up. CONCLUSIONS: TAVI by subclavian retrograde approach seems safe and feasible in inoperable/high-risk patients with AS and peripheral vasculopathy, who are neither eligible for surgical valve replacement nor transfemoral percutaneous aortic valve implantation. Further studies are needed to evaluate the long-term efficacy of this new therapy.

Is it possible to percutaneously close an atrial septal defect in babies who weigh less than four kilograms? Report of a successful case.

A 14-mm Amplatzer septal occluder was implanted in a 3.8-kg baby with a fenestrated atrial septal defect. The patient was eligible for percutaneous closure because of the high surgical risk due to his poor condition. In conclusion, despite the low weight of the baby, the Amplatzer septal occluder proved to be safe and effective.