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Background Patients with early breast cancer (EBC) achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) have a favorable prognosis. Breast surgery might be avoided in patients in whom the presence of residual tumor can be ruled out with high confidence. Here, we investigated the diagnostic accuracy of contrast-enhanced MRI (CE-MRI) in predicting pCR and long-term outcome after NACT. Methods Patients with EBC, including patients with locally advanced disease, who had undergone CE-MRI after NACT, were retrospectively analyzed ( n  = 246). Three radiologists, blinded to clinicopathologic data, reevaluated all MRI scans regarding to the absence (radiologic complete remission; rCR) or presence (no-rCR) of residual contrast enhancement. Clinical and pathologic responses were compared categorically using Cohen’s kappa statistic. The Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). Results Overall rCR and pCR (no invasive tumor in the breast and axilla (ypT0/is N0)) rates were 45% (111/246) and 29% (71/246), respectively. Only 48% (53/111; 95% CI 38–57%) of rCR corresponded to a pCR (= positive predictive value - PPV). Conversely, in 87% (117/135; 95% CI 79–92%) of patients, residual tumor observed on MRI was pathologically confirmed (= negative predictive value - NPV). Sensitivity to detect a pCR was 75% (53/71; 95% CI 63–84%), while specificity to detect residual tumor and accuracy were 67% (117/175; 95% CI 59–74%) and 69% (170/246; 95% CI 63–75%), respectively. The PPV was significantly lower in hormone-receptor (HR)-positive compared to HR-negative tumors (17/52 = 33% vs. 36/59 = 61%; P  = 0.004). The concordance between rCR and pCR was low (Cohen’s kappa − 0.1), however in multivariate analysis both assessments were significantly associated with RFS (rCR P  = 0.037; pCR P  = 0.033) and OS (rCR P = 0.033; pCR P  = 0.043). Conclusion Preoperative CE-MRI did not accurately predict pCR after NACT for EBC, especially not in HR-positive tumors. However, rCR was strongly associated with favorable RFS and OS.

PurposeIntensive care unit (ICU) hospitalization is challenging for the family members of the patients. Most family members report some level of anxiety and depression, sometimes even resulting in post-traumatic stress disorder (PTSD). An association has been reported between lack of information and PTSD. This study had three aims: to quantify the psychological burden of family members of critically ill patients, to explore whether a website with specific information could reduce PTSD symptoms, and to ascertain whether a website with information about intensive care would be used.MethodA multicenter double-blind, randomized, placebo-controlled trial was carried out in Austria and Switzerland.ResultsIn total, 89 members of families of critically ill patients (mean age 47.3 ± 12.9 years, female n = 59, 66.3%) were included in the study. 46 relatives were allocated to the intervention website and 43 to the control website. Baseline Impact of Event Scale (IES) score was 27.5 ± 12.7. Overall, 50% showed clinically relevant PTSD symptoms at baseline. Mean IES score for the primary endpoint (~ 30 days after inclusion, T1) was 24 ± 15.8 (intervention 23.9 ± 17.9 vs. control 24.1 ± 13.5, p = 0.892). Hospital Anxiety and Depression Scale (HADS - Deutsch (D)) score at T1 was 12.2 ± 6.1 (min. 3, max. 31) and did not differ between groups. Use of the website differed between the groups (intervention min. 1, max. 14 vs. min. 1, max. 3; total 1386 “clicks” on the website, intervention 1021 vs. control 365). Recruitment was prematurely stopped in February 2020 due to coronavirus disease 2019 (COVID-19).ConclusionFamily members of critically ill patients often have significant PTSD symptoms and online information on critical illness did not result in reduced PTSD symptoms.

Measuring the resilience of historic areas is challenging due to their heterogeneity in scale, heritage type, multi-hazard exposure, and socio-cultural context, creating the need for a flexible framework aligned with the latest Intergovernmental Panel on Climate Change (IPCC) approaches. This study introduces the SHELTER framework, which takes the historic area as its primary unit of analysis while enabling a cross-scalar assessment, from artefact/building scale to urban and transregional contexts. Developed through a co-creation strategy and an extensive literature review, the framework integrates indicators for multidimensional, cross-scale, and systemic resilience assessment and monitoring. The indicators span hazards such as heatwaves, earthquakes, floods, subsidence, and wildfires and capture exposure and vulnerability, the latter being understood as the sensitivity and coping, adaptive, and transformative capacities of communities. Refinement using the RACER methodology yielded a concise yet comprehensive shortlist of indicators, providing both general overviews and specific insights tailored to historic environments. The framework’s efficacy was tested across five case studies, demonstrating adaptability and suitability in diverse historic areas. Overall, SHELTER moves beyond a traditional focus on physical vulnerability and risk management, offering a replicable, holistic set of resilience indicators that supports consistent assessment and monitoring while respecting the singularities of historic settings.

To date, it is unclear which factors trigger or cause the severe course of disease. [...]there is only limited evidence concerning extrapulmonary manifestations of COVID-19. [...]a subgroup of COVID-19 patients exhibit a hyperinflammatory pattern similar to secondary hemophagocytic lymphohistiocytosis (sHLH) [1, 2], a syndrome that can be triggered by viruses like EBV. [...]we speculated whether critically ill COVID-19 patients show evidence of EBV- or CMV-infection or reactivation and quantified EBV as well as CMV DNA levels in blood by PCR. [...]levels of EBV viremia correlate with IL-6 in COVID-19 patients but not in non-COVID-19 patients. Since EBV can induce immune dysregulation and expression of IL-6 in peripheral blood mononuclear cells (PBMCs) via deoxyuridine triphosphate nucleotidohydrolase (dUTPase) in vitro [3], one might speculate that EBV acts as an additional inflammatory trigger in critically ill COVID-19 patients. [...]we compared COVID-19 patients to an appropriate control group.

We present the VROnSite platform that supports immersive training of first responder units’ on-site squad leaders. Our training platform is fully immersive, entirely untethered to ease use and provides two means of navigation—abstract and natural walking—to simulate stress and exhaustion, two important factors for decision making. With the platform’s capabilities, we close a gap in prior art for first responder training. Our research is closely interlocked with stakeholders from multiple fire brigades to gather early feedback in an iterative design process. In this paper, we present the system’s design rationale, provide insight into the process of training scenario development and present results of a user study with 41 squad leaders from the firefighting domain. Virtual disaster environments with two different navigation types were evaluated using quantitative and qualitative measures. Participants considered our platform highly suitable for training of decision making in complex first responder scenarios and results show the importance of the provided navigation technologies in this context.

PurposeThe optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes.MethodsPreplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization.ResultsA total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome.ConclusionsProtective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.

PurposeThe 2021 guidelines endorsed by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) recommend using highly malignant electroencephalogram (EEG) patterns (HMEP; suppression or burst-suppression) at > 24 h after cardiac arrest (CA) in combination with at least one other concordant predictor to prognosticate poor neurological outcome. We evaluated the prognostic accuracy of HMEP in a large multicentre cohort and investigated the added value of absent EEG reactivity.MethodsThis is a pre-planned prognostic substudy of the Targeted Temperature Management trial 2. The presence of HMEP and background reactivity to external stimuli on EEG recorded > 24 h after CA was prospectively reported. Poor outcome was measured at 6 months and defined as a modified Rankin Scale score of 4–6. Prognostication was multimodal, and withdrawal of life-sustaining therapy (WLST) was not allowed before 96 h after CA.Results845 patients at 59 sites were included. Of these, 579 (69%) had poor outcome, including 304 (36%) with WLST due to poor neurological prognosis. EEG was recorded at a median of 71 h (interquartile range [IQR] 52–93) after CA. HMEP at > 24 h from CA had 50% [95% confidence interval [CI] 46–54] sensitivity and 93% [90–96] specificity to predict poor outcome. Specificity was similar (93%) in 541 patients without WLST. When HMEP were unreactive, specificity improved to 97% [94–99] (p = 0.008).ConclusionThe specificity of the ERC-ESICM-recommended EEG patterns for predicting poor outcome after CA exceeds 90% but is lower than in previous studies, suggesting that large-scale implementation may reduce their accuracy. Combining HMEP with an unreactive EEG background significantly improved specificity. As in other prognostication studies, a self-fulfilling prophecy bias may have contributed to observed results.

Introduction Acute kidney injury is a frequent complication in critically ill patients with and without COVID-19. The aim of this study was to evaluate the incidence of, and risk factors for, acute kidney injury and its effect on clinical outcomes of critically ill COVID-19 patients in Tyrol, Austria. Methods This multicenter prospective registry study included adult patients with a SARS-CoV-2 infection confirmed by polymerase chain reaction, who were treated in one of the 12 dedicated intensive care units during the COVID-19 pandemic from February 2020 until May 2022. Results In total, 1042 patients were included during the study period. The median age of the overall cohort was 66 years. Of the included patients, 267 (26%) developed acute kidney injury during their intensive care unit stay. In total, 12.3% ( n  = 126) required renal replacement therapy with a median duration of 9 (IQR 3–18) days. In patients with acute kidney injury the rate of invasive mechanical ventilation was significantly higher with 85% ( n  = 227) compared to 41% ( n  = 312) in the no acute kidney injury group ( p  < 0.001). The most important risk factors for acute kidney injury were invasive mechanical ventilation (OR = 4.19, p  < 0.001), vasopressor use ( OR  = 3.17, p  < 0.001) and chronic kidney disease (OR = 2.30, p  < 0.001) in a multivariable logistic regression analysis. Hospital and intensive care unit mortality were significantly higher in patients with acute kidney injury compared to patients without acute kidney injury (Hospital mortality: 52.1% vs. 17.2%, p  < 0.001, ICU-mortality: 47.2% vs. 14.7%, p  < 0.001). Conclusion As in non-COVID-19 patients, acute kidney injury is clearly associated with increased mortality in critically ill COVID-19 patients. Among known risk factors, invasive mechanical ventilation has been identified as an independent and strong predictor of acute kidney injury. Graphical abstract