Thomas Ardiles

INTRODUCTION: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. METHODS: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. RESULTS: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. CONCLUSIONS: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01209169.

BACKGROUND: Agitation and delirium are common in mechanically ventilated adult intensive care unit (ICU) patients and may contribute to delayed extubation times. Difficult-to-wean ICU patients have been associated with an increased risk of longer ICU length of stays and mortality. The purpose of this systematic review and meta-analysis is to evaluate the evidence of dexmedetomidine facilitating successful mechanical ventilation extubation in difficult-to-wean ICU patients and clinical outcomes. METHODS: A literature search was conducted using MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Global Health, Cochrane Central Register of Controlled Trials, Clinical Trial Registries, and the Health Technology Assessment Database from inception to December 5, 2019. Randomized controlled trials evaluating dexmedetomidine with the intended purpose to facilitate mechanical ventilation liberation in adult ICU patients (≥18 years) experiencing extubation failure were included. The primary outcome of time to extubation was evaluated using the weighted mean difference (WMD), with a random effects model. Secondary analyses included hospital and ICU length of stay, in-hospital mortality, hypotension, and bradycardia. RESULTS: = .005) and ICU length of stay (WMD: -3.04 days; 95% CI: -4.66 to -1.43). Hypotension risk was increased with dexmedetomidine (risk ratio [RR]: 1.62, 95% CI: 1.05-2.51), but there was no difference in bradycardia risk (RR: 3.98, 95% CI: 0.70-22.78). No differences were observed in mortality rates (RR: 1.30, 95% CI: 0.45-3.75) or hospital length of stay (WMD: -2.67 days; 95% CI: -7.73 to 2.39). CONCLUSIONS: Dexmedetomidine was associated with a significant reduction in the time to extubation and shorter ICU stay in difficult-to-wean ICU patients. Although hypotension risk was increased with dexmedetomidine, no differences in other clinical outcomes were observed.

OBJECTIVES: To evaluate the relationship among ICU patient-to-pharmacist ratio, perceived quality of patient care, and pharmacist burnout. DESIGN: A prospective, multicenter, time-motion study conducted over a 10-month period (from May 1, 2022, to February 28, 2023). SETTING: Adult ICU, PICU, or neonatal ICU. SUBJECTS: ICU clinical pharmacists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 128 ICU pharmacists completed 703 unique time-motion observation days and recorded their time associated with direct/indirect patient care activities, Maslach Burnout Inventor survey scores, and perceived quality of patient care provided (5-point Likert scale). Total pharmacist time on direct and indirect patient care activities were 5.9 ± 1.9 and 3.3 ± 1.7 hours per shift, respectively. The number of assigned patients in the ICU and overall (ICU and non-ICU) per shift was 19.3 ± 12.9 and 23.4 ± 17.9, respectively. The overall frequency of pharmacist burnout was 38.1%. Burnout was associated with incremental increases in the number of assigned total patients (odds ratio [OR], 1.03; 95% CI, 1.01-1.05) and overtime worked (OR, 1.18; 95% CI, 1.03-1.35). Higher compared with lower perceived quality of patient care was associated with significantly smaller assigned ICU patients (17.0 ± 7.4 vs. 30.6 ± 23.8, respectively; p < 0.001). Additional direct patient care time allocated per patient was predictive of a high quality of care perception (OR, 1.53; 95% CI, 1.03-2.05). Burnout was inversely associated with high quality of care (OR, 0.59; 95% CI, 0.36-0.96). The ICU patient-to-pharmacist ratio between 16:1 and 19:1 was associated with the highest perceived quality of patient care and comprehensive patient assessment completion rates. CONCLUSIONS: Critical care pharmacist practice models across healthcare institutions are inconsistent regarding patient assignments and time allocated toward direct and indirect patient care activities. The ICU patient-to-pharmacist ratio range between 16:1 and 19:1 may optimize quality of care and burnout risk at large academic institutions.

Acute and chronic pulmonary complications are a very important cause of morbidity and mortality in sickle cell disease. The Acute Chest Syndrome (ACS) is the most common form of acute pulmonary disease and will be reviewed in this article. Early recognition and aggressive treatment of ACS are important for successful management. The development of pulmonary hypertension is a very important cause of chronic pulmonary disease and contributes to mortality. Because of the increased numbers of sickle cell patients living to adulthood, it is important for primary care providers to become familiar with these complications.

Polymyositis-dermatomyositis (PM-DM) is a chronic inflammatory disorder that mainly involves muscles and skin. Clinically amyopathic dermatomyositis (CADM) is a unique subset of PM-DM with typical skin manifestations but little or no evidence of musculoskeletal involvement. Many cases of dermatomyositis and CADM are associated with internal malignancy, but pulmonary manifestations can also been seen; the most common of which is interstitial lung disease. Pleural effusion is a rare complication and may be difficult to differentiate from other causes, such as infections, heart failure, or malignancy. We report a patient with CADM complicated by rapidly progressive pleural effusions. Based on findings of this patient, as well as literature review, we suggest that the etiology of massive pleural effusion in this setting is most likely related to local immune pleuritis associated with underlying interstitial lung disease due to dermatomyositis. Optimal management should be individualized and may include immunosuppressive agents, as well as antimicrobials, and potentially other agents.