Post-intensive care syndrome and health-related quality of life in long-term survivors of cardiac arrest: a prospective cohort study.

Patients discharged from intensive care are at risk for post-intensive care syndrome (PICS), which consists of physical, psychological, and/or neurological impairments. This study aimed to analyze PICS at 24 months follow-up, to identify potential risk factors for PICS, and to assess health-related quality of life in a long-term cohort of adult cardiac arrest survivors. This prospective cohort study included adult cardiac arrest survivors admitted to the intensive care unit of a Swiss tertiary academic medical center. The primary endpoint was the prevalence of PICS at 24 months follow-up, defined as impairments in physical (measured through the European Quality of Life 5-Dimensions-3-Levels instrument [EQ-5D-3L]), neurological (defined as Cerebral Performance Category Score > 2 or Modified Rankin Score > 3), and psychological (based on the Hospital Anxiety and Depression Scale and the Impact of Event Scale-Revised) domains. Among 107 cardiac arrest survivors that completed the 2-year follow-up, 46 patients (43.0%) had symptoms of PICS, with 41 patients (38.7%) experiencing symptoms in the physical domain, 16 patients (15.4%) in the psychological domain, and 3 patients (2.8%) in the neurological domain. Key predictors for PICS in multivariate analyses were female sex (adjusted odds ratio [aOR] 3.17, 95% CI 1.08 to 9.3), duration of no-flow interval during cardiac arrest (minutes) (aOR 1.17, 95% CI 1.02 to 1.33), post-discharge job-loss (aOR 31.25, 95% CI 3.63 to 268.83), need for ongoing psychological support (aOR 3.64, 95% CI 1.29 to 10.29) or psychopharmacologic treatment (aOR 9.49, 95% CI 1.9 to 47.3), and EQ-visual analogue scale (points) (aOR 0.88, 95% CI 0.84 to 0.93). More than one-third of cardiac arrest survivors experience symptoms of PICS 2 years after resuscitation, with the highest impairment observed in the physical and psychological domains. However, long-term survivors of cardiac arrest report intact health-related quality of life when compared to the general population. Future research should focus on appropriate prevention, screening, and treatment strategies for PICS in cardiac arrest patients.

Efficacy and Tolerability of Intranasal Midazolam Administration for Antiseizure Treatment in Adults: A Systematic Review.

OBJECTIVE: The objective of this study was to assess the efficacy and tolerability of intranasal midazolam (in-MDZ) administration for antiseizure treatment in adults. METHODS: Embase and Medline literature databases were searched. We included randomized trials and cohort studies (excluding case series) of adult patients (≥ 18 years of age) examining in-MDZ administration for epilepsy, epileptic seizures, or status epilepticus published in English between 1985 and 2022. Studies were screened for eligibility based on predefined criteria. The primary outcome was the efficacy of in-MDZ administration, and the secondary outcome was its tolerability. Extracted data included study design, patient characteristics, intervention details, and outcomes. Risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: A total of 12 studies with 929 individuals treated with in-MDZ were included. Most studies were retrospective, with their number increasing over time. Administered in-MDZ doses ranged from 2.5 to 20 mg per single dose. The mean proportion of successful seizure termination after first in-MDZ administration was 72.7% (standard deviation [SD] 18%), and the proportion of seizure recurrence or persistent seizures ranged from 61 to 75%. Most frequent adverse reactions to in-MDZ were dizziness (mean 23.5% [SD 38.6%]), confusion (one study; 17.4%), local irritation (mean 16.6% [SD 9.6%]), and sedation (mean 12.7% [SD 9.7%]). CONCLUSIONS: Administration of in-MDZ seems promising for the treatment of prolonged epileptic seizures and seizure clusters in adults. Limited evidence suggests that intranasal administration is safe. Further research is warranted because of the heterogeneity of cohorts, the variation in dosages, and the lack of uniformity in defining successful seizure termination.

Absent leptomeningeal collateralization is associated with greatest benefit from mechanical thrombectomy in the 6-24 hour time window.

INTRODUCTION: The impact of leptomeningeal collateralization on the efficacy of mechanical thrombectomy (MT) in patients with anterior circulation large vessel occlusion (aLVO) presenting in the 6-24 h time window remains poorly elucidated. PATIENTS AND METHODS: Retrospective multicenter study of aLVO patients presenting between 6 and 24 h after stroke onset who received MT plus Best Medical Treatment (BMT) or BMT alone. Leptomeningeal collateralization was assessed using single-phase computed tomography angiography (grade 0: no filling; grade 1: filling ⩽50%; grade 2: filling >50% but <100%; grade 3: filling 100% of the occluded territory). Inverse probability of treatment weighted ordinal regression was performed to assess the association between treatment and shift of the modified Rankin Scale (mRS) score toward lower categories at 3 months. We used interaction analysis to explore differential treatment effects on functional outcomes (probabilities for each mRS subcategory at 3 months) at different collateral grades. RESULTS: Among 363 included patients, 62% received MT + BMT. Better collateralization was associated with better functional outcomes at 3 months in the BMT alone group (collateral grade 1 vs 0: acOR 5.06, 95% CI 2.33-10.99). MT + BMT was associated with higher odds of favorable functional outcome at 3 months (acOR 1.70, 95% CI 1.11-2.62) which was consistent after adjustment for collateral status (acOR 1.54, 95% CI 1.01-2.35). Regarding treatment effect modification, patients with absent collateralization had higher probabilities for a mRS of 0-4 and a lower mortality at 3 months for the MT + BMT group. DISCUSSION AND CONCLUSION: In the 6-to-24-h time window, aLVO patients with absent leptomeningeal collateralization benefit most from MT + BMT, indicating potential advantages for this group despite their poorer baseline prognosis.

Prediction of outcomes after cardiac arrest by a generative artificial intelligence model.

Aims: To investigate the prognostic accuracy of a non-medical generative artificial intelligence model (Chat Generative Pre-Trained Transformer 4 - ChatGPT-4) as a novel aspect in predicting death and poor neurological outcome at hospital discharge based on real-life data from cardiac arrest patients. Methods: This prospective cohort study investigates the prognostic performance of ChatGPT-4 to predict outcomes at hospital discharge of adult cardiac arrest patients admitted to intensive care at a large Swiss tertiary academic medical center (COMMUNICATE/PROPHETIC cohort study). We prompted ChatGPT-4 with sixteen prognostic parameters derived from established post-cardiac arrest scores for each patient. We compared the prognostic performance of ChatGPT-4 regarding the area under the curve (AUC), sensitivity, specificity, positive and negative predictive values, and likelihood ratios of three cardiac arrest scores (Out-of-Hospital Cardiac Arrest [OHCA], Cardiac Arrest Hospital Prognosis [CAHP], and PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages [PROLOGUE score]) for in-hospital mortality and poor neurological outcome. Results: Mortality at hospital discharge was 43% (n = 309/713), 54% of patients (n = 387/713) had a poor neurological outcome. ChatGPT-4 showed good discrimination regarding in-hospital mortality with an AUC of 0.85, similar to the OHCA, CAHP, and PROLOGUE (AUCs of 0.82, 0.83, and 0.84, respectively) scores. For poor neurological outcome, ChatGPT-4 showed a similar prediction to the post-cardiac arrest scores (AUC 0.83). Conclusions: ChatGPT-4 showed a similar performance in predicting mortality and poor neurological outcome compared to validated post-cardiac arrest scores. However, more research is needed regarding illogical answers for potential incorporation of an LLM in the multimodal outcome prognostication after cardiac arrest.

Performance of large language models on advocating the management of meningitis: a comparative qualitative study.

OBJECTIVES: We aimed to examine the adherence of large language models (LLMs) to bacterial meningitis guidelines using a hypothetical medical case, highlighting their utility and limitations in healthcare. METHODS: A simulated clinical scenario of a patient with bacterial meningitis secondary to mastoiditis was presented in three independent sessions to seven publicly accessible LLMs (Bard, Bing, Claude-2, GTP-3.5, GTP-4, Llama, PaLM). Responses were evaluated for adherence to good clinical practice and two international meningitis guidelines. RESULTS: A central nervous system infection was identified in 90% of LLM sessions. All recommended imaging, while 81% suggested lumbar puncture. Blood cultures and specific mastoiditis work-up were proposed in only 62% and 38% sessions, respectively. Only 38% of sessions provided the correct empirical antibiotic treatment, while antiviral treatment and dexamethasone were advised in 33% and 24%, respectively. Misleading statements were generated in 52%. No significant correlation was found between LLMs' text length and performance (r=0.29, p=0.20). Among all LLMs, GTP-4 demonstrated the best performance. DISCUSSION: Latest LLMs provide valuable advice on differential diagnosis and diagnostic procedures but significantly vary in treatment-specific information for bacterial meningitis when introduced to a realistic clinical scenario. Misleading statements were common, with performance differences attributed to each LLM's unique algorithm rather than output length. CONCLUSIONS: Users must be aware of such limitations and performance variability when considering LLMs as a support tool for medical decision-making. Further research is needed to refine these models' comprehension of complex medical scenarios and their ability to provide reliable information.

Misconceptions and do-not-resuscitate preferences of healthcare professionals commonly involved in cardiopulmonary resuscitations: A national survey.

Aims: To assess the DNR preferences of critical care-, anesthesia- and emergency medicine practitioners, to identify factors influencing decision-making, and to raise awareness for misconceptions concerning CPR outcomes. Methods: A nationwide multicenter survey was conducted in Switzerland confronting healthcare professionals with a case vignette of an adult patient with an out-of-hospital cardiac arrest (OHCA). The primary outcome was the rate of DNR Code Status vs. CPR Code Status when taking the perspective from a clinical case vignette of a 70-year-old patient. Secondary outcomes were participants' personal preferences for DNR and estimates of survival with good neurological outcome after in- and out-of-hospital cardiac arrest. Results: Within 1803 healthcare professionals, DNR code status was preferred in 85% (n = 1532) in the personal perspective of the case vignette and 53.2% (n = 932) when making a decision for themselves. Main predictors for a DNR Code Status regarding the case vignette included preferences for DNR Code Status for themselves (n [%] 896 [58.5] vs. 87 [32.1]; adjusted odds ratio [OR] 2.97, 95% confidence interval [CI] 2.25-3.92; p < 0.001) and lower estimated OHCA survival (mean [±SD] 12.3% [±11.8] vs. 14.7%[±12.8]; adjusted OR 0.98, 95% CI 0.97-0.99; p = 0.001). Physicians chose a DNR order more often when compared to nurses and paramedics. Conclusions: The estimation of outcomes following cardiac arrest and personal living conditions are pivotal factors influencing code status preferences in healthcare professionals. Healthcare professionals should be aware of cardiac arrest prognosis and potential implications of personal preferences when engaging in code status- and end-of-life discussions with patients and their relatives.

Violence against healthcare professionals in intensive care units: a systematic review and meta-analysis of frequency, risk factors, interventions, and preventive measures.

BACKGROUND: To assess the frequency, risk factors, consequences, and prevention of violence against healthcare workers in intensive care units. METHODS: PubMed, Scopus, Google Scholar, EMBASE, Cochrane, and Web of Science were searched for studies on violence against healthcare workers in adult intensive care units. Risk factors, patient characteristics, and implications for healthcare workers were collected. Study quality, bias, and level of evidence were assessed using established tools. RESULTS: Seventy-five studies with 139,533 healthcare workers from 32 countries were included. The overall median frequency of violence was 51% (IQR 37-75%). Up to 97% of healthcare workers experienced verbal violence, and up to 82% were victims of physical violence. Meta-analysis of frequency revealed an average frequency of 31% (95% CI 22-41%) for physical violence, 57% for verbal violence (95% CI 48-66%), and 12% for sexual violence (95% CI 4-23%). Heterogeneity was high according to the I2 statistics. Patients were the most common perpetrators (median 56%), followed by visitors (median 22%). Twenty-two studies reported increased risk ratios of up to 2.3 or odds ratios of up to 22.9 for healthcare workers in the ICU compared to other healthcare workers. Risk factors for experiencing violence included young age, less work experience, and being a nurse. Patients who exhibited violent behavior were often male, older, and physically impaired by drugs. Violence was underreported in up to 80% of cases and associated with higher burnout rates, increased anxiety, and higher turnover intentions. Overall the level of evidence was low. CONCLUSIONS: Workplace violence is frequent and underreported in intensive care units, with potential serious consequences for healthcare workers, calling for heightened awareness, screening, and preventive measures. The potential risk factors for violence should be further investigated. SYSTEMATIC REVIEW REGISTRATION: The protocol for this review was registered with Prospero on January 15, 2023 (ID CRD42023388449).

Sustained effort network for treatment of status epilepticus/European academy of neurology registry on adult refractory status epilepticus (SENSE-II/AROUSE).

BACKGROUND: Status Epilepticus (SE) is a common neurological emergency associated with a high rate of functional decline and mortality. Large randomized trials have addressed the early phases of treatment for convulsive SE. However, evidence regarding third-line anesthetic treatment and the treatment of nonconvulsive status epilepticus (NCSE) is scarce. One trial addressing management of refractory SE with deep general anesthesia was terminated early due to insufficient recruitment. Multicenter prospective registries, including the Sustained Effort Network for treatment of Status Epilepticus (SENSE), have shed some light on these questions, but many answers are still lacking, such as the influence exerted by distinct EEG patterns in NCSE on the outcome. We therefore initiated a new prospective multicenter observational registry to collect clinical and EEG data that combined may further help in clinical decision-making and defining SE. METHODS: Sustained effort network for treatment of status epilepticus/European Academy of Neurology Registry on refractory Status Epilepticus (SENSE-II/AROUSE) is a prospective, multicenter registry for patients treated for SE. The primary objectives are to document patient and SE characteristics, treatment modalities, EEG, neuroimaging data, and outcome of consecutive adults admitted for SE treatment in each of the participating centers and to identify factors associated with outcome and refractoriness. To reach sufficient statistical power for multivariate analysis, a cohort size of 3000 patients is targeted. DISCUSSION: The data collected for the registry will provide both valuable EEG data and information about specific treatment steps in different patient groups with SE. Eventually, the data will support clinical decision-making and may further guide the planning of clinical trials. Finally, it could help to redefine NCSE and its management. TRIAL REGISTRATION: NCT number: NCT05839418.

Association Between Dose Escalation of Anesthetics and Outcomes in Patients With Refractory Status Epilepticus.

BACKGROUND AND OBJECTIVES: To investigate the association between dose escalation of continuously administered IV anesthetics and its duration with short-term outcomes in adult patients treated for refractory status epilepticus (RSE). METHODS: Clinical and electroencephalographic data of patients with RSE without hypoxic-ischemic encephalopathy who were treated with anesthetics at a Swiss academic medical center from 2011 to 2019 were assessed. The frequency of anesthetic dose escalation (i.e., dose increase) and its associations with in-hospital death or return to premorbid neurologic function were primary endpoints. Multivariable logistic regression analysis was performed to identify associations with endpoints. RESULTS: Among 111 patients with RSE, doses of anesthetics were escalated in 57%. Despite patients with dose escalation having a higher morbidity (lower Glasgow Coma Scale [GCS] score at status epilepticus [SE] onset, more presumably fatal etiologies, longer duration of SE and intensive care, more infections, and arterial hypotension) as compared with patients without, the primary endpoints did not differ between these groups in univariable analyses. Multivariable analyses revealed decreased odds for death with dose escalation (odds ratio 0.09, 95% CI 0.01-0.86), independent of initial GCS score, presumably fatal etiology, SE severity score, SE duration, and nonconvulsive SE with coma, with similar functional outcome among survivors compared with patients without dose escalation. DISCUSSION: Our study reveals that anesthetic dose escalation in adult patients with RSE is associated with decreased odds for death without increasing the proportion of surviving patients with worse neurofunctional state than before RSE. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that anesthetic dose escalation decreases the odds of death in patients with RSE.

Concurrence of seizures and peri-ictal delirium in the critically ill - its frequency, associated characteristics, and outcomes.

BACKGROUND: To assess the frequency, clinical features, and outcome of peri-ictal delirium in adult patients experiencing seizures during intensive care. METHODS: This observational study was conducted at a Swiss intensive care unit from 2015 to 2020. Patients aged ≥ 18 years with seizures were categorized as peri-ictal delirious (Intensive Care Delirium Screening Checklist [i.e., ICDSC] ≥ 4) or not (i.e., ICDSC < 4) within 24 h of seizures. The frequency of peri-ictal delirium and in-hospital death were defined as the primary endpoints. Illness severity and treatment characteristics between delirious and non-delirious patients were secondary endpoints. Logistic regression was used to compare in-hospital death and differences regarding clinical characteristics between delirious and non-delirious patients. RESULTS: 48% of 200 patients had peri-ictal delirium for a median of 3 days. Delirious patients were older (median age 69 vs. 62 years, p = 0.002), had lower Simplified Acute Physiology Scores II (SAPS II; median 43 vs. 54, p = 0.013), received neuroleptics more frequently (31 vs. 5%, p < 0.001), were mechanically ventilated less often (56% vs. 73%, p = 0.013) and shorter (median 3 vs. 5 days, p = 0.011), and had decreased odds for in-hospital death with delirium (OR = 0.41, 95% CI 0.20-0.84) in multivariable analyses. CONCLUSIONS: Delirium emerged in every second patient experiencing seizures and was associated with lower SAPS II, shorter mechanical ventilation, and better outcomes, contradicting assumptions that altered cerebral function, from seizures and delirium, are linked to unfavorable outcomes.

Translation of patients' advance directives in intensive care units: are we there yet?

OBJECTIVES: This review examined studies regarding the implementation and translation of patients' advance directives (AD) in intensive care units (ICUs), focusing on practical difficulties and obstacles. METHODS: The digital PubMed and Medline databases were screened using predefined keywords to identify relevant prospective and retrospective studies published until 2022. RESULTS: Seventeen studies from the United States, Europe, and South Africa (including 149,413 patients and 1210 healthcare professionals) were identified. The highest prevalence of ADs was described in a prospective study in North America (49%), followed by Central Europe (13%), Asia (4%), Australia and New Zealand (4%), Latin America (3%), and Northern and Southern Europe (2.6%). While four retrospective studies reported limited effects of ADs, four retrospective studies, one survey and one systematic review indicated significant effects on provision of intensive care, higher rates of do-not-resuscitate orders, and care withholding in patients with ADs. Four of these studies showed shorter ICU stays, and lower treatment costs in patients with ADs. One prospective and two retrospective studies reported issues with loss, delayed or no transmission of ADs. One survey revealed that 91% of healthcare workers did not regularly check for ADs. Two retrospective studies and two survey revealed that the implementation of directives is further challenged by issues with their applicability, phrasing, and compliance by the critical care team and family members. CONCLUSIONS: Although ADs may improve intensive- and end-of-life care, insufficient knowledge, lack of awareness, poor communication between healthcare providers and patients or surrogates, lack of standardization of directives, as well as ethical and legal concerns challenge their implementation.

Neurological evolution of severe baclofen intoxication: from brain death mimic to recovered brain function.

Patients with brain death have by definition irreversible and complete loss of brainstem reflexes. Before a definite diagnosis of brain death can be confirmed, all potential confounders must be thoroughly excluded. Baclofen intoxication is a rare cause of brain death mimic characterised by transient deep coma and absence of brainstem reflexes and might be mistaken with brain death. We report the case of a female patient in her 70s who ingested baclofen with suicidal intent and was admitted with a deep coma and loss of all brainstem reflexes and a spontaneous burst-suppression pattern in the electroencephalography which resolved over 10 hours. After a state mimicking brain death for 6 hours, the patient experienced complete recovery. Severe baclofen intoxication can mimic brain death clinically and is associated with temporary pathological electroencephalographic findings. Awareness of this toxidrome is crucial, as appropriate management can lead to full recovery.

Red blood cell distribution width for the prediction of outcomes after cardiac arrest.

The red blood cell distribution width (RDW) is a routinely available blood marker that measures the variation of the size/volume of red blood cells. The aim of our study was to investigate the prognostic value of RDW in cardiac arrest patients and to assess whether RDW improves the prognostic value of three cardiac arrest-specific risk scores. Consecutive adult cardiac arrest patients admitted to the ICU of a Swiss university hospital were included. The primary outcome was poor neurological outcome at hospital discharge assessed by Cerebral Performance Category. Of 702 patients admitted to the ICU after cardiac arrest, 400 patients (57.0%) survived, of which 323 (80.8%) had a good neurological outcome. Higher mean RDW values showed an independent association with poor neurological outcomes at hospital discharge (adjusted OR 1.27, 95% CI 1.14 to 1.41; p < 0.001). Adding the maximum RDW value to the OHCA- CAHP- and PROLOGUE cardiac arrest scores improved prognostic performance. Within this cohort of cardiac arrest patients, RDW was an independent outcome predictor and slightly improved three cardiac arrest-specific risk scores. RDW may therefore support clinical decision-making.

Sex-related differences in adult patients with status epilepticus: a seven-year two-center observation.

BACKGROUND: Conflicting findings exist regarding the influence of sex on the development, treatment, course, and outcome of status epilepticus (SE). Our study aimed to investigate sex-related disparities in adult SE patients, focusing on treatment, disease course, and outcome at two Swiss academic medical centers. METHODS: In this retrospective study, patients treated for SE at two Swiss academic care centers from Basel and Geneva from 2015 to 2021 were included. Primary outcomes were return to premorbid neurologic function, death during hospital stay and at 30 days. Secondary outcomes included characteristics of treatment and disease course. Associations with primary and secondary outcomes were assessed using multivariable logistic regression. Analysis using propensity score matching was performed to account for the imbalances regarding age between men and women. RESULTS: Among 762 SE patients, 45.9% were women. No sex-related differences were found between men and women, except for older age and lower frequency of intracranial hemorrhages in women. Compared to men, women had a higher median age (70 vs. 66, p = 0.003), had focal nonconvulsive SE without coma more (34.9% vs. 25.5%; p = 0.005) and SE with motor symptoms less often (52.3% vs. 63.6%, p = 0.002). With longer SE duration (1 day vs. 0.5 days, p = 0.011) and a similar proportion of refractory SE compared to men (36.9% vs. 36.4%, p = 0.898), women were anesthetized and mechanically ventilated less often (30.6% vs. 42%, p = 0.001). Age was associated with all primary outcomes in the unmatched multivariable analyses, but not female sex. In contrast, propensity score-matched multivariable analyses revealed decreased odds for return to premorbid neurologic function for women independent of potential confounders. At hospital discharge, women were sent home less (29.7% vs. 43.7%, p < 0.001) and to nursing homes more often (17.1% vs. 10.0%, p = 0.004). CONCLUSIONS: This study identified sex-related disparities in the clinical features, treatment modalities, and outcome of adult patients with SE with women being at a disadvantage, implying that sex-based factors must be considered when formulating strategies for managing SE and forecasting outcomes.

Apical pulmonary lesions suspected of malignancy visible on neck CT angiography performed for acute stroke: Prevalence, treatment, and clinical implications - the PLEURA study.

BACKGROUND: Computed tomography angiography (CTA) of the supraaortic arteries is commonly used for acute stroke workup and may reveal apical pulmonary lesions (APL). AIM: To determine the prevalence, follow-up algorithms, and in-hospital outcomes of stroke patients with APL on CTA. METHODS: We retrospectively included consecutive adult patients with ischemic stroke, transient ischemic attack, or intracerebral hemorrhage and available CTA at a tertiary hospital between January 2014 and May 2021. We reviewed all CTA reports for the presence of APL. APL were classified as malignancy suspicious or benign appearing based on radiological-morphological criteria. We performed regression analyses to investigate the impact of malignancy suspicious APL on different in-hospital outcome parameters. RESULTS: Among 2715 patients, APL on CTA were found in 161 patients (5.9% [95%CI: 5.1-6.9]; 161/2715). Suspicion of malignancy was present in one third of patients with APL (36.0% [95%CI: 29.0-43.7]; 58/161), 42 of whom (72.4% [95%CI: 60.0-82.2]; 42/58) had no history of lung cancer or metastases. When performed, further investigations confirmed primary or secondary pulmonary malignancy in three-quarters (75.0% [95%CI: 50.5-89.8]; 12/16), with two patients (16.7% [95%CI: 4.7-44.8]; 2/12) receiving de novo oncologic therapy. In multivariable regression, the presence of radiologically malignancy suspicious APL was associated with higher NIHSS scores at 24 h (beta = 0.67, 95%CI: 0.28-1.06, p = 0.001) and all-cause in-hospital mortality (aOR = 3.83, 95%CI: 1.29-9.94, p = 0.01). CONCLUSIONS: One in seventeen patients shows APL on CTA, of which one-third is malignancy suspicious. Further work-up confirmed pulmonary malignancy in a substantial number of patients triggering potentially life-saving oncologic therapy.

Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.

BACKGROUND AND AIMS: To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19). METHODS: We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL. RESULTS: We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively. CONCLUSIONS: Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.

External validation of the PROLOGUE score to predict neurological outcome in adult patients after cardiac arrest: a prospective cohort study.

BACKGROUND: The PROLOGUE score (PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages) is a novel prognostic model for the prediction of neurological outcome after cardiac arrest, which showed exceptional performance in the internal validation. The aim of this study is to validate the PROLOGUE score in an independent cohort of unselected adult cardiac arrest patients and to compare it to the thoroughly validated Out-of-Hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP) scores. METHODS: This study included consecutive adult cardiac arrest patients admitted to the intensive care unit (ICU) of a Swiss tertiary teaching hospital between October 2012 and July 2022. The primary endpoint was poor neurological outcome at hospital discharge, defined as a Cerebral Performance Category (CPC) score of 3 to 5 including death. RESULTS: Of 687 patients included in the analysis, 321 (46.7%) survived to hospital discharge with good neurological outcome, 68 (9.9%) survived with poor neurological outcome and 298 (43.4%) died. The PROLOGUE score showed an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI 0.80 to 0.86) and good calibration for the prediction of the primary outcome. The OHCA and CAHP score showed similar performance (AUROC 0.83 and 0.84 respectively), the differences between the three scores were not significant (p = 0.495). In a subgroup analysis, the PROLOGUE score performed equally in out-of-hospital and in-hospital cardiac arrest patients whereas the OHCA and CAHP score performed significantly better in OHCA patients. CONCLUSION: The PROLOGUE score showed good prognostic accuracy for the early prediction of neurological outcome in adult cardiac arrest survivors in our cohort and might support early goals-of-care discussions in the ICU. Trial registration Not applicable.