No abstract

Rapid response teams (RRT), alternatively termed medical emergency teams, have become part of the clinical landscape in the majority of adult hospitals throughout Australia and New Zealand. These teams aim to bring critical care expertise to the bedside of clinically deteriorating patients residing in general hospital wards with the aim of preventing adverse outcomes, in particular death or cardiorespiratory arrests. While the concept of RRT has considerable face validity, there is little high quality evidence of their effectiveness and much uncertainty as to the optimal methods for identifying patients in need of RRT and calling the RRT (afferent limb) and how, and with whom, the RRT should then respond (efferent limb). Adverse unintended consequences of RRT systems and the opportunity costs involved in maintaining such systems have not been subject to study, amid concerns RRT may be compensating for other potentially remediable system of care failures. This article presents an overview of the current state of play of RRT in hospital practice as they pertain to the care of adult patients and identifies several issues around their implementation and evaluation that should be subject to further research.

No abstract

Relatively few RRT activations are associated with acute resuscitation plans, and most interventions during RRT responses are low level. The high rate of post-RRT deaths and transfers to higher-level care units calls for the prospective identification of such patients in targeting appropriate care.

Purpose The Acute Disease Quality Initiative (ADQI) Workgroup recently released a consensus definition of sepsis-associated acute kidney injury (SA-AKI), combining Sepsis-3 and Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria. This study aims to describe the epidemiology of SA-AKI. Methods This is a retrospective cohort study carried out in 12 intensive care units (ICUs) from 2015 to 2021. We studied the incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes of SA-AKI based on the ADQI definition. Results Out of 84,528 admissions, 13,451 met the SA-AKI criteria with its incidence peaking at 18% in 2021. SA-AKI patients were typically admitted from home via the emergency department (ED) with a median time to SA-AKI diagnosis of 1 day (interquartile range (IQR) 1–1) from ICU admission. At diagnosis, most SA-AKI patients (54%) had a stage 1 AKI, mostly due to the low urinary output (UO) criterion only (65%). Compared to diagnosis by creatinine alone, or by both UO and creatinine criteria, patients diagnosed by UO alone had lower renal replacement therapy (RRT) requirements (2.8% vs 18% vs 50%; p < 0.001), which was consistent across all stages of AKI. SA-AKI hospital mortality was 18% and SA-AKI was independently associated with increased mortality. In SA-AKI, diagnosis by low UO only, compared to creatinine alone or to both UO and creatinine criteria, carried an odds ratio of 0.34 (95% confidence interval (CI) 0.32–0.36) for mortality. Conclusion SA-AKI occurs in 1 in 6 ICU patients, is diagnosed on day 1 and carries significant morbidity and mortality risk with patients mostly admitted from home via the ED. However, most SA-AKI is stage 1 and mostly due to low UO, which carries much lower risk than diagnosis by other criteria. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-023-07138-0.

Inactivated whole-cell vaccines present a full repertoire of antigens to the immune system. Formalin treatment, a standard method for microbial inactivation, can modify or destroy protein antigenic epitopes. We tested the hypothesis that photochemical inactivation with psoralen and UVA light (PUVA), which targets nucleic acid, would improve the immunogenicity of an Enterotoxigenic E. coli (ETEC) vaccine relative to a formalin-inactivated counterpart. Exposure of ETEC H10407 to PUVA using the psoralen drug 4′-Aminomethyltrioxsalen hydrochloride (AMT) yielded replication-incompetent bacteria that retained their metabolic activity. CFA/I-mediated mannose-resistant hemagglutination (MRHA) was equivalent for PUVA-inactivated and live ETEC, but was severely reduced for formalin–ETEC, indicating that PUVA preserved fimbrial protein functional integrity. The immunogenicity of PUVA–ETEC and formalin–ETEC was compared in mice ± double mutant heat-labile enterotoxin (dmLT) adjuvant. Two weeks after an intramuscular prime/boost, serum anti-ETEC IgG titers were similar for the two vaccines and were increased by dmLT. However, the IgG responses raised against several conserved ETEC proteins were greater after vaccination with PUVA–ETEC. In addition, PUVA–ETEC generated IgG specific for heat-labile toxin (LT) in the absence of dmLT, which was not a property of formalin–ETEC. These data are consistent with PUVA preserving ETEC protein antigens in their native-like form and justify the further testing of PUVA as a vaccine platform for ETEC using murine challenge models.

Purpose of the studyDespite mature rapid response systems (RRS) for clinical deterioration, individuals activating RRS have poor outcomes, with up to one in four dying in hospital. We aimed to derive and validate a risk prediction tool for estimating risk of 28-day mortality among hospitalised patients following rapid response team (RRT) activation.Study designAnalysis of prospectively collected data on 1151 consecutive RRT activations involving 800 inpatients at a tertiary adult hospital. Patient characteristics, RRT triggers and actions, and mortality were ascertained from medical records and death registries. A multivariable risk prediction regression model, derived from 600 randomly selected patients, was validated in the remaining 200 patients. Main outcome was accuracy of weighted risk score (measured by area under receiver operator curve (AUC)) and performance characteristics for various cut-off scores.ResultsAt 28 days, 150 (18.8%) patients had died. Increasing age, emergency admission, chronic liver disease, chronic kidney disease, malignancy, after-hours RRT activation, increasing National Early Warning Score, major/intense RRT intervention and multiple RRT activations were predictors of mortality. The risk score (0–105) in derivation and validation cohorts had AUCs 0.86 (95% CI 0.82 to 0.89) and 0.82 (95% CI 0.75 to 0.90), respectively. In the validation cohort, cut-off score of 32.5 or higher maximised sensitivity: 81.6% (95% CI 68.4% to 92.1%), specificity: 56.2% (95% CI 49.4% to 63.6%), positive likelihood ratio (LR): 1.9 (95% CI 1.5 to 2.3) and negative LR: 0.3 (95% CI 0.2 to 0.6).ConclusionA validated risk score predicted risk of post-RRT death with more than 80% accuracy, helping to identify patients for whom targeted rescue care may improve survival.

Hemangioblastomas are benign tumors of undetermined origin, and account for up to 2.5% of all intracranial tumors. They may occur either sporadically or as a manifestation of von Hippel-Lindau (VHL) syndrome. Central nervous system (CNS) hemangioblastomas are pathologically diagnosed by gross and microscopic morphology, with further support of the diagnosis conferred by a characteristic immunohistochemistry profile including PAX8 negativity. Although renal hemangioblastomas have previously been reported to be PAX8 positive, CNS hemangioblastoma positive PAX8 expression has never been reported. We reviewed 11 cases of cerebellar hemangioblastoma from our institution over a 7-year period (2010 to 2017). Tissue was stained for PAX8 to determine immunohistochemical labeling. Of 11 reviewed cases of cerebellar hemangioblastoma, 7 exhibited PAX8 immunohistochemical expression. A review of the literature found no previously reported cases of positive PAX8 labeling in cerebellar hemangiomas. PAX8 negativity is not as specific for cerebellar hemangioblastoma as previously thought, and caution must be used when relying solely on a panel of PAX2, PAX8, and inhibin A for pathologic diagnosis.