High-flow nasal oxygen versus conventional oxygen therapy and noninvasive ventilation in COVID-19 respiratory failure: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Noninvasive methods of respiratory support, including noninvasive ventilation (NIV), continuous positive airway pressure (CPAP), and high-flow nasal oxygen (HFNO), are potential strategies to prevent progression to requirement for invasive mechanical ventilation in acute hypoxaemic respiratory failure. The COVID-19 pandemic provided an opportunity to understand the utility of noninvasive respiratory support among a homogeneous cohort of patients with contemporary management of acute respiratory distress syndrome. We performed a network meta-analysis of studies evaluating the efficacy of NIV (including CPAP) and HFNO, compared with conventional oxygen therapy (COT), in patients with COVID-19. METHODS: PubMed, Embase, and the Cochrane library were searched in May 2023. Standard random-effects meta-analysis was used first to estimate all direct pairwise associations and the results from all studies were combined using frequentist network meta-analysis. Primary outcome was treatment failure, defined as discontinuation of HFNO, NIV, or COT despite progressive disease. Secondary outcome was mortality. RESULTS: We included data from eight RCTs with 2302 patients, (756 [33%] assigned to COT, 371 [16%] to NIV, and 1175 [51%] to HFNO). The odds of treatment failure were similar for NIV (P=0.33) and HFNO (P=0.25), and both were similar to that for COT (reference category). The odds of mortality were similar for all three treatments (odds ratio for NIV vs COT: 1.06 [0.46-2.44] and HFNO vs COT: 0.97 [0.57-1.65]). CONCLUSIONS: Noninvasive ventilation, high-flow nasal oxygen, and conventional oxygen therapy are comparable with regards to treatment failure and mortality in COVID-19-associated acute respiratory failure. PROSPERO REGISTRATION: CRD42023426495.

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.

Subclinical Contrast-Induced Acute Kidney Injury in Patients Undergoing Cerebral Computed Tomography.

INTRODUCTION: The nephrotoxicity of modern contrast media remains controversial. Novel biomarkers of kidney damage may help in identifying a subclinical structural renal injury not revealed by widely used markers of kidney function. OBJECTIVE: The aim of this study was to investigate clinical (contrast-induced acute kidney injury [CI-AKI]) and subclinical CI-AKI (SCI-AKI) after intra-arterial administration of Iodixanol and Iopamidol in patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. METHODS: This is a prospective observational monocentric study. Urinary sample was collected at 4-8 h after contrast medium exposure to measure neutrophil gelatinase associated lipocalin (NGAL) and the product tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), while blood samples were collected at 24 and 48 h after exposure to measure serum creatinine. RESULTS: One hundred patients were enrolled, of whom 53 were exposed to Iodixanol and 47 to Iopamidol. Patients in Iodixanol and Iopamidol groups were comparable in terms of demographics, pre-procedural and procedural data. No patient developed CI-AKI according KDIGO criteria, while 13 patients reported SCI-AKI after exposure to iodine-based medium contrast (3 patients in Iodixanol group and 10 patients in Iopamidol group), defined by positive results of NGAL and/or [TIMP-2] × [IGFBP7]. A positive correlation was found between NGAL and [TIMP-2] × [IGFBP7] in the analysed population (Spearman's rho 0.49, p < 0.001). In logistic regression analysis, Iopamidol exposure showed higher risk for SCI-AKI compared to Iodixanol (OR 4.5 [95% CI 1.16-17.52], p = 0.030), even after controlling for eGFR and volume of contrast medium used. CONCLUSIONS: This study showed that intra-arterial modern contrast media administration may have a nephrotoxic effect in a population without pre-existing chronic kidney disease. Further investigations on larger scale are warranted to confirm if Iopamidol exposed patients to increased risk of SCI-AKI compared to Iodixanol.

Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein-7 (IGFBP7) levels are associated with adverse outcomes in patients in the intensive care unit with acute kidney injury.

The G1 cell cycle inhibitors tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as novel biomarkers for the prediction of moderate to severe acute kidney injury (AKI) risk. However, the prognostic value of [TIMP-2]•[IGFBP7] in predicting adverse outcomes in intensive care unit (ICU) patients with AKI was not previously described. To evaluate this, we conducted a cohort study, measuring [TIMP2]•[IGFBP7] levels in critically ill patients admitted to the ICU and classified the patients as NephroCheck (NC) (+) or NC (-) according to [TIMP-2]•[IGFBP7] values and AKI (+) or AKI (-) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We then evaluated the incidence of continuous renal replacement therapy initiation, all-cause mortality and a composite endpoint of both in the four groups. Baseline [TIMP-2]•[IGFBP7] values were available for 719 patients, of whom 239 developed AKI and 151 met the composite endpoint. Compared to NC (-)/AKI (+) patients, NC (+)/AKI (+) patients had a significant risk of ICU mortality and the composite endpoint. Kaplan-Meier curves showed that the survival estimate for the composite endpoint of NC (+)/AKI (+) patients was 34.4%; significantly worse than NC (-)/AKI (+) patients (67.4%). Multivariate analyses showed strong association between NC positivity and the composite endpoint. The inflammatory marker, procalcitonin, was an additional prognostic biomarker to compare and confirm the incremental value of NephroCheck. No association between procalcitonin and the composite endpoint was found, especially in patients with AKI, suggesting that NephroCheck may be more kidney specific. Thus, the [TIMP-2]•[IGFBP7] values can serve to identify patients with AKI at increased risk for adverse outcomes in the ICU.

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.

The impact of implementing the single provider model of emergency medicine in a paediatric hospital: a retrospective cohort analysis.

STUDY OBJECTIVE: The Meyer Pediatric Hospital in Florence, Italy recently implemented the single provider model of emergency medicine. Prior to these changes, patients were triaged to a paediatric surgeon or paediatrician based on the complaint. The authors assess the outcomes of patients evaluated by surgeons prior to this change and compare them with those of patients seen by emergency physicians. METHODS: A retrospective, cohort study was performed reviewing patients seen in the emergency department between 2005 and 2008 for the three most common surgical complaints encountered before the systems change: head trauma, testicular pain and abdominal pain. Outcomes include misdiagnoses, consultation rates, dispositions, imaging, interventions and surgeries. RESULTS: A total of 2415 patient visits were included. Emergency physicians saw more patients (1388 vs 1027) and obtained more consultations (25.6% vs 8.1%) than surgeons. Patients triaged directly to surgeons were more likely to be admitted to the hospital (10.3% vs 7.6%), undergo urgent interventions (9.5% vs 6.7%), undergo surgery (8.0% vs 4.8%), have more radiographic images to evaluate head trauma (12.1% vs 5.3%), be misdiagnosed (1.0% vs 0.3%) and have more plain films for abdominal pain (3.1% vs 1.3%). There is an overall trend towards fewer missed diagnoses by emergency physicians (0.3% vs 0.9%), but this difference is only statistically significant in the abdominal pain subset analysis (p=0.032, combined data p=0.052). CONCLUSIONS: The single provider model of emergency medicine where emergency physicians manage all patients presenting to the emergency department appears to be a safe and efficient model of emergency medical care.