3-month Outcome Research Articles

The implications of poor nutritional status on outcomes of geriatric trauma patients

BackgroundMalnutrition is shown to be associated with worse outcomes among surgical patients, yet its postdischarge outcomes in trauma patients are not clear. This study aimed to evaluate both index admission and postdischarge outcomes of geriatric trauma patients who are at risk of poor nutritional status. MethodsThis is a secondary analysis of the prospective observational American Association of Surgery for Trauma Frailty Multi-institutional Trial. Geriatric (≥65 years) patients presenting to 1 of the 17 Level I/II/III trauma centers (2019–2021) were included and stratified using the simplified Geriatric Nutritional Risk Index (albumin [g/dL] + body mass index [kg/m2]/10) into severe (simplified Geriatric Nutritional Risk Index <5), moderate (5.5> simplified Geriatric Nutritional Risk Index ≥5), mild level of nutritional risk (6> simplified Geriatric Nutritional Risk Index ≥5.5), and good nutritional status (simplified Geriatric Nutritional Risk Index ≥6) and compared. ResultsOf the 1,321 patients enrolled, 22% were at risk of poor nutritional status (mild: 13%, moderate: 7%, severe: 3%). The mean age was 77 ± 8 years, and the median [interquartile range] Injury Severity Score was 9 [5–13]. Patients at risk of poor nutritional status had greater rates of sepsis, pneumonia, discharge to the skilled nursing facility and rehabilitation center, index-admission mortality, and 3-month mortality (P < .05). On multivariable analyses, being at risk of severe level of nutritional risk was independently associated with sepsis (adjusted odds ratio 6.21, 95% confidence interval 1.68–22.90, P = .006), pneumonia (adjusted odds ratio 4.40, 95% confidence interval 1.21–16.1, P = .025), index-admission mortality (adjusted odds ratio 3.16, 95% confidence interval 1.03–9.68, P = .044), and 3-month mortality (adjusted odds ratio 8.89, 95% confidence interval 2.01–39.43, P = .004) compared with good nutrition state. ConclusionNearly one quarter of geriatric trauma patients were at risk of poor nutritional status, which was identified as an independent predictor of worse index admission and 3-month postdischarge outcomes. These findings underscore the need for nutritional screening at admission.

Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial

Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial. TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed. We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overall survival was slightly better in the endovascular thrombectomy group compared with medical treatment only (adjusted hazard ratio 0·70 [95% CI 0·50-0·99]). In patients with acute ischaemic stroke from large vessel occlusion with established large infarct, compared with medical treatment only, endovascular thrombectomy was associated at 12 months after stroke with better functional outcome, quality of life, and overall survival. These findings suggest that the benefits of endovascular thrombectomy in patients with an ischaemic stroke and a large infarct are sustained in the long term and support the use of endovascular thrombectomy in these patients. European Union Horizon 2020 Research and Innovation Programme.

Using Multimodal Assessments to Reevaluate Depression Designations for Spine Surgery Candidates.

Depression is common in spine surgery candidates and may influence postoperative outcomes. Ecological momentary assessments (EMAs) can overcome limitations of existing depression screening methods (e.g., recall bias, inaccuracy of historical diagnoses) by longitudinally monitoring depression symptoms in daily life. In this study, we compared EMA-based depression assessment with retrospective self-report (a 9-item Patient Health Questionnaire [PHQ-9]) and chart-based depression diagnosis in lumbar spine surgery candidates. We further examined the associations of each depression assessment method with surgical outcomes. Adult patients undergoing lumbar spine surgery (n = 122) completed EMAs quantifying depressive symptoms up to 5 times daily for 3 weeks preoperatively. Correlations (rank-biserial or Spearman) among EMA means, a chart-based depression history, and 1-time preoperative depression surveys (PHQ-9 and Psychache Scale) were analyzed. Confirmatory factor analysis was used to categorize PHQ-9 questions as somatic or non-somatic; subscores were compared with a propensity score-matched general population cohort. The associations of each screening modality with 6-month surgical outcomes (pain, disability, physical function, pain interference) were analyzed with multivariable regression. The association between EMA Depression scores and a depression history was weak (rrb = 0.34 [95% confidence interval (CI), 0.14 to 0.52]). Moderate correlations with EMA-measured depression symptoms were observed for the PHQ-9 (rs = 0.51 [95% CI, 0.37 to 0.63]) and the Psychache Scale (rs = 0.68 [95% CI, 0.57 to 0.76]). Compared with the matched general population cohort, spine surgery candidates endorsed similar non-somatic symptoms but significantly greater somatic symptoms on the PHQ-9. EMA Depression scores had a stronger association with 6-month surgical outcomes than the other depression screening modalities did. A history of depression in the medical record is not a reliable indication of preoperative depression symptom severity. Cross-sectional depression assessments such as PHQ-9 have stronger associations with daily depression symptoms but may conflate somatic depression symptoms with spine-related disability. As an alternative to these methods, mobile health technology and EMAs provide an opportunity to collect real-time, longitudinal data on depression symptom severity, potentially improving prognostic accuracy. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Developing a nomogram model for 3-month prognosis in patients who had an acute ischaemic stroke after intravenous thrombolysis: a multifactor logistic regression model approach

ObjectivesThis study is to establish a nomination graph model for individualised early prediction of the 3-month prognosis of patients who had an acute ischaemic stroke (AIS) receiving intravenous thrombolysis with...

Protective Effects of Early Neonatal Methylxanthine Treatment on Cognitive and Language Outcomes in Premature Infants with and without High-Risk Perinatal Factors.

Caffeine and theophylline are methylxanthines and nonselective adenosine antagonists commonly used to treat apnea of prematurity. Both human and animal data suggest that xanthines also have clinically important long-term neuroprotective effects in the presence of inflammation in the perinatal period as seen following hypoxic-ischemic brain insults. Moreover, these protective effects appear to be more robust when administered shortly (&lt;48 h) after preterm birth. To evaluate the importance of the postdelivery therapeutic window, we collected and analyzed medical data from preterm infants meeting criteria (23-30 weeks' gestational age [GA]), born at the University of Connecticut Health Center (UCHC), and cared for at the UCHC/Connecticut Children's Medical Center (CCMC) NICU from 1991 to 2017 (n = 858). Eighteen-month follow-up data included cognitive and language scores from the Neonatal Neurodevelopmental Follow-Up Clinic records, with a retention of 81% of subjects (n = 696). Differences were analyzed via multivariate ANOVA and ANCOVA. Analyses showed that infants who received xanthine treatment within the first 48 h after preterm birth showed significantly better 18-month behavioral outcomes than those treated later than 48 h, despite a lack of a priori differences in GA, birth, or length of stay. The positive effect of early xanthine therapy was particularly robust for infants exposed prenatally to the inflammatory conditions of chorioamnionitis and/or preeclampsia. Current findings are consistent with human and animal data, showing that caffeine exerts protective effects, at least in part via attenuation of inflammation. Results add to the evidence supporting routine immediate prophylactic neuroprotective xanthine therapy (i.e., caffeine) in preterm infants. Findings also add important new evidence of the augmented value of caffeine for infants with inflammatory exposure due to mothers with preeclampsia or chorioamnionitis.

Unlocking the Potential of the HEART Pathway: Predicting MACE and Facilitating Nurse-Physician Collaboration in Chest Pain Unit.

The HEART pathway serves as a tool for predicting major adverse cardiac events (MACE) among patients presenting with acute chest pain, aiding in early discharge of low-risk patients and reducing unnecessary cardiac investigations. This study aimed to evaluate physician-nurse reliability of the HEART pathway. Moreover investigates the efficacy of HEART pathway to predict 3-month MACE in patients with acute chest pain. We conducted a prospective study on 97 patients experiencing acute chest pain. A team of three professionals - a nurse, a cardiology resident, and a cardiology attending physician - performed risk stratification. We assessed inter-rater reliability among the raters as well as explored 3-month MACE outcomes. Excellent pairwise agreements were found between the raters. Overall agreement among raters was excellent, with an ICC of 0.84 (95% CI: 0.73 - 0.97). The HEART pathway score exhibited strong predictive power (AUC: 0.85) for 3-month MACE. At a cut-off score of 4, sensitivity, specificity, and negative predictive values were 87.5%, 58.9%, and 95.8%, respectively. The HEART pathway score effectively predicts 3-month MACE in patients with acute non-traumatic chest pain. Moreover, the high agreement among the attending physician, the resident physician, and the nurse suggests that nurses could use this tool, potentially reducing the workload on physicians.

Low serum alanine aminotransferase (ALT) levels are associated with poor outcomes in acute ischemic stroke patients regardless of age

Studies have indicated that reduced serum ALT levels are commonly linked to aging and are known to predict poor outcomes in many clinical conditions as potential frailty indicators. There are close connections between the brain and peripheral organs, particularly the liver. In patients with acute ischemic stroke (AIS), the interactive effects may change ALT levels, which in turn influence stroke outcomes. Whether ALT has potential neuroprotective effects or is an indicator of frailty in AIS patients remains unknown.This retrospective analysis examined 572 AIS patients in Beijing Luhe Hospital between August 2020 and June 2021. Patient demographics and laboratory results were assembled. The National Institutes of Health Stroke Scale (NIHSS) was used to analyze stroke severity. Modified Rankin Score (mRS) determined stroke outcome 3 months after AIS, with mRS≤2 indicating a favorable outcome. Based on serum ALT measurements, patients were classified into three tertiles (T1-T3). Binary logistic regression analysis evaluated the correlation between ALT tertiles and AIS outcomes.Of the patients, 66 exhibited unfavorable outcomes. The median ALT level in this group was 13 (IQR: 11–18.25), which was lower than in the favorable outcomes cohort (16; IQR: 11–22). A decline in ALT corresponded with a higher incidence of poor outcomes at 3 months (T1, 15.5 %; T2, 11.4 %; T3, 7.0 %; p = 0.03). The lowest ALT tertile (T1) was independently linked to an adverse 3-month outcome (OR 2.50 95 %CI 1.24–5.07, p = 0.038) compared to the highest tertile. ALT levels demonstrated no correlation with age (T1, 62.59 ± 12.64; T2, 64.01 ± 11.47; T3, 65.12 ± 11.27; p > 0.05).Regardless of age, lower serum ALT levels are independently associated with poorer outcomes in AIS patients. This finding suggests the potential pivotal part of the liver in AIS outcomes, highlighting the need to consider both neurological and liver functions post-stroke.

Females and Housing First: An analysis of 18-month outcomes in a randomized controlled trial.

The main objective of this research was to qualitatively examine the impacts of Housing First (HF) specifically on those participants who identified themselves as female in response to question asking what their gender was. The data analyzed are from a larger, muti-site, randomized controlled trial. χ2 analysis was used to compare the life changes (coded as positive, neutral, or negative) experienced by 64 females (42 HF and 22 TAU). An in-depth qualitative analysis was conducted on 45 of these participants (23 HF and 22 TAU). Significantly more female HF participants reported making positive life changes from baseline to 18-month than those in TAU. Relative to females in TAU, female HF participants reported a number of specific positive changes, including enhanced safety, improved recovery in mental illness, greater reductions in drug use, and individual changes. The implications of findings for strengthening HF programs to meet the unique needs of female participants are discussed.

Intracranial Pressure Thresholds for Cerebral Autoregulation Impairment: Age-Stratified Analysis of Ultra-Low-Frequency Pressure Reactivity Index (UL-PRx) in Traumatic Brain Injury.

The study investigated the effectiveness of low-frequency sampling in detecting alterations in cerebrovascular reactivity (CVR) associated with changes in intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across different age groups. The primary objective was to investigate an ICP threshold that indicates a decrease in CVR as evidenced by a significant increase in the ultra-low-frequency pressure reactivity index (UL-PRx). Additionally, the study aimed to develop an age-based categorization method for patients with TBI to investigate the differences between these ICP thresholds in different age groups. In this retrospective analysis, data from 263 patients with TBI were prospectively collected. ICP and mean arterial pressure were extracted from the hospital database at 5-min intervals. Demographic details, clinical presentation, computed tomography scans, neurosurgical interventions, and 12-months outcome were recorded. ICP versus UL-PRx values were categorized into ICP bins and graphically represented with boxplots for each age group, illustrating how as ICP values rise, there is a bin (age-tailored ICP [AT-ICP]) beyond which UL-PRx shows a sudden increase, indicating CVR loss. Homogeneous age groups were established to obtain a consistent AT-ICP threshold. The discriminatory ability of the AT-ICP thresholds was compared with the guideline-recommended thresholds by calculating the area under the Receiver Operating Characteristic curve of the ICP-derived indices (dose above threshold, and the hourly dosage above threshold). Age groups 0-5, 6-20, 21-60, 61-70, and 71-85years were the best age subdivisions, corresponding to AT-ICP thresholds of 20, 30, 35, 25, and 30mmHg, respectively. The AT-ICP thresholds exhibited better discriminative ability compared with the guideline-recommended thresholds. The AT-ICP thresholds offer a novel approach for estimating CVR impairment and the developed method represents an alternative solution to address the age stratification issue in patients with TBI.

High blood glucose variability may predict poor outcomes in patients with spontaneous cerebellar hemorrhage undergoing surgical operation: a retrospective study

BackgroundElevated blood glucose (BG) variability has been reported as an independent risk factor for poor prognosis in a variety of diseases. This study aimed to investigate the association between BG variability and clinical outcomes in patients with spontaneous cerebellar hemorrhage (SCH) undergoing surgical operation.MethodsThis retrospective cohort study of the consecutive patients admitted to the department of Neurosurgery, the Affiliated Hospital of Qingdao University between January 2014 and June 2022 with the diagnosis of SCH underwent surgical intervention. BG analysis was continuously and routinely performed. BG variability was represented by the standard deviation (SD) of the serial measurements within the first 7 days. The general characteristics, imageological information, blood glucose level, and surgical information were reviewed and compared through medical records.ResultsA total of 115 patients (65 male and 50 female) were enrolled. Out of all 115 patients, the overall clinical outcomes according to the modified Rankin Scale (mRS) were poor (mRS 3–6) in 31 patients (26.96%) and good (mRS 0–2) in 84 patients (73.04%). Twelve of the 115 patients died during hospitalization, and the mortality rate was 10.43%. Multivariate logistic regression analysis showed that SD of BG (odds ratio (OR), 4.717; 95% confidence interval (CI), 1.054–21.115; P = 0.043), GCS (OR, 0.563; 95% CI, 0.330–0.958; P = 0.034), and hematoma volume (OR, 1.395; 95% CI, 1.118–1.748; P = 0.003) were significant predictors. The area under the ROC curve of SD of BG was 0.911 (95% CI, 0.850–0.973; P < 0.001) with a sensitivity and specificity of 90.3% and 83.3%, respectively, and the cut-off value was 1.736.ConclusionsHigh BG Variability is independently correlated with the 6-month poor outcomes in patients with SCH undergoing surgical operation.

Inpatient Skin-to-skin Care Predicts 12-Month Neurodevelopmental Outcomes in Very Preterm Infants

To examine the relationship between inpatient skin-to-skin care rates and neurodevelopmental scores measured at 12months in very preterm (VPT) infants. From a retrospective review of medical records of 181 VPT infants (<32weeks gestational age [GA] at birth), we derived skin-to-skin care rate, ie, total minutes of skin-to-skin care each infant received over the number of days of hospital stay. We used scores on the Capute Scales from routine follow-up assessments at 12months to measure neurodevelopmental outcomes. Families averaged approximately 17minutes/day of skin-to-skin care (2days/week, 70minutes/session), although there was substantial variability. Variation in skin-to-skin rate was positively associated with outcomes at 12months corrected age (r=0.25, P<.001). Skin-to-skin rate significantly predicted 6.2% unique variance in 12-month neurodevelopmental outcomes, after adjusting for GA, socioeconomic status (SES), health acuity, and visitation frequency. A 20-minute increase in skin-to-skin care per day was associated with a 10-point increase (0.67 SDs) in neurodevelopmental outcomes at 12months. GA and infant health acuity did not moderate these relations. VPT infants who experienced more skin-to-skin care during hospitalization demonstrated higher scores on 12-month neurodevelopmental assessments. Results provide evidence that skin-to-skin care confers extended benefits to VPT infants through the first year of life. Skin-to-skin care offers promise as a family-centered intervention designed to promote positive developmental outcomes in at-risk infants.

The Impact of Sex and Arterial Stiffness Interactions on the Outcome after an Acute Ischemic Stroke: A Retrospective Cohort Study.

Background/Objectives: Arterial stiffness (AS) is an independent predictor of cardiovascular events and is associated with a poor prognosis. While AS may represent a novel therapeutic target, recent evidence shows that it is sexually dimorphic. The aim of this study was to evaluate relative sex differences in arterial stiffness and their possible impact on the outcome of acute ischemic stroke. Methods: We retrospectively evaluated a cohort of adult patients with the following inclusion criteria: acute ischemic stroke, which occurred within 24 h from the onset of symptoms, confirmed through neuroimaging examinations, additional evaluations including extracranial and transcranial arterial ultrasound examinations, transthoracic echocardiography, a 12-lead resting ECG, and continuous 24 h in-hospital blood pressure monitoring. Based on the 24 h blood pressure monitoring, the following parameters were evaluated: systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and arterial stiffness index (ASI). The modified Rankin scale (mRS) was assessed at 90 days to evaluate the 3-month clinical outcome, defining an unfavorable outcome as an mRS score ≥ 3. To assess the factors associated with unfavorable outcomes, a stepwise logistic regression model was performed on the total sample size, and the analyses were replicated after stratifying by sex. Results: A total of 334 patients (176 males, 158 females) were included in the analysis. There was a significant sex-dependent impact of ASI on the 90-day unfavorable Rankin score (mRS score ≥ 3) as only men had a reduced likelihood of favorable outcomes with increasing arterial stiffness (OR:1.54, 95% CI: 1.06-2.23; P-interaction = 0.023). Conclusions: The influence of ASI on the 3-month functional outcome after acute ischemic stroke is at least in part sex-related, suggesting that, in males, higher ASI values are associated with a worse outcome.

Three-month treatment outcome of medication-overuse headache according to classes of overused medications, use of acute medications, and preventive treatments

Medication overuse headache (MOH) is a chronic headache disorder that results from excessive use of acutely symptomatic headache medications, leading to more frequent and severe headaches. This study aims to assess the 3-month treatment outcomes in MOH patients, focusing on the types and usage of overused medications, as well as preventive treatments. This prospective cross-sectional study analyzed the treatment outcomes of 309 MOH patients from April 2020 to March 2022. Patients were advised to discontinue overused medications immediately and offered preventive treatments based on clinical judgment. Data on headache characteristics, medication use, and impact on daily life were collected at baseline and 3 months. Results showed overall significant improvements in headache-related variables in patients completing the 3-month treatment follow-up. The median number of headache days per month decreased from 15 days at baseline to 8 days after 3 months (p < 0.001). Patients who overused multiple drug classes demonstrated increased disability levels (mean Headache Impact Test-6 score: 62 at baseline vs. 56 at 3 months, p < 0.01). Those who continued overusing medications reported more days of severe headache (mean 18 days at baseline vs. 14 days at 3 months, p < 0.05) and greater impact (mean Migraine Disability Assessment score: 35 at baseline vs. 28 after 3 months, p < 0.05) compared to the baseline. Differences in headache outcomes were evident across different preventive treatment groups, with generalized estimating equation analyses highlighting significant associations between clinical characteristics, overused medication classes, and preventive treatments. Most MOH clinical features significantly improved after 3 months of treatment. However, notable interactions were observed with certain clinical presentations, suggesting possible influences of overused medication classes, usage patterns, and preventive treatment types on MOH treatment outcomes. This study underscores the importance of individualized treatment strategies and the potential benefits of discontinuing overused medications.

Effect of a peer-led emergency department behavioral intervention on non-fatal opioid overdose: 18-month outcome in the Navigator randomized controlled trial.

Emergency departments (EDs) provide an opportunity to identify people at risk of overdose and reduce the risk. We evaluated the effect of an ED behavioral intervention delivered by peer recovery support specialists (PRSSs) on non-fatal opioid overdose. Two-arm, randomized trial. Two EDs in Rhode Island, USA. ED patients presenting with an opioid overdose, complications of opioid use disorder or a recent history of opioid overdose (November 2018-May 2021). Among 648 participants, the mean age was 36.9years, 68.2% were male and 68.5% were White. Participants were randomized to receive a behavioral intervention from a PRSS (n = 323) or a licensed clinical social worker (LICSW) (n = 325). PRSS and LICSW used evidence-based interviewing and intervention techniques, informed by their lived experience (PRSS) or clinical theory and practice (LICSW). We identified non-fatal opioid overdoses in the 18 months following the ED visit through linkage to statewide emergency medical services data using a validated case definition. The primary outcome was any non-fatal opioid overdose during the 18-month follow-up period. Among 323 participants randomized to the PRSS arm, 81 (25.1%) had a non-fatal opioid overdose during follow-up, compared with 95 (29.2%) of 325 participants randomized to the LICSW arm (P = 0.24). There was no statistically significant difference in the effectiveness of randomization to the PRSS arm versus the LICSW arm on the risk of non-fatal opioid overdose, adjusting for the history of previous overdose (relative risk = 0.86, 95% confidence interval = 0.67-1.11). In Rhode Island, USA, over one-in-four emergency department patients at high risk of overdose experience a non-fatal opioid overdose in the 18 months post-discharge. We found no evidence that the risk of non-fatal opioid overdose differs for emergency department patients receiving a behavioral intervention from a peer recovery support specialist versus a licensed clinical social worker.

Evaluating and Updating the IMPACT Model to Predict Outcomes in Two Contemporary North American Traumatic Brain Injury Cohorts.

The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) model is a widely recognized prognostic model applied after traumatic brain injury (TBI). However, it was developed with patient cohorts that may not reflect modern practice patterns in North America. We analyzed data from two sources: the placebo arm of the phase II double-blinded, multicenter, randomized controlled trial Prehospital Tranexamic Acid for TBI (TXA) cohort and an observational cohort with similar inclusion/exclusion criteria (Predictors of Low-risk Phenotypes after Traumatic Brain Injury Incorporating Proteomic Biomarker Signatures [PROTIPS] cohort). All three versions of the IMPACT model-core, extended, and laboratory-were evaluated for 6-month mortality (Glasgow Outcome Scale Extended [GOSE] = 1) and unfavorable outcomes (GOSE = 1-4). Calibration (intercept and slope) and discrimination (area under the receiver operating characteristic curve [ROC-AUC]) were used to assess model performance. We then compared three model updating methods-recalibration in the large, logistic recalibration, and coefficient update-with the best update method determined by likelihood ratio tests. In our calibration analysis, recalibration improved both intercepts and slopes, indicating more accurate predicted probabilities when recalibration was done. Discriminative performance of the IMPACT models, measured by AUC, showed mortality prediction ROCs between 0.61 and 0.82 for the TXA cohort, with the coefficient updated Lab model achieving the highest at 0.84. Unfavorable outcomes had lower AUCs, ranging from 0.60 to 0.79. Similarly, in the PROTIPS cohort, AUCs for mortality ranged from 0.75 to 0.82, with the coefficient updated Lab model also showing superior performance (AUC 0.84). Unfavorable outcomes in this cohort presented AUCs from 0.67 to 0.73, consistently lower than mortality predictions. The closed testing procedure using likelihood ratio tests consistently identified the coefficient update model as superior, outperforming the original and recalibrated models across all cohorts. In our comprehensive evaluation of the IMPACT model, the coefficient updated models were the best performing across all cohorts through a structured closed testing procedure. Thus, standardization of model updating procedures is needed to reproducibly determine the best performing versions of IMPACT that reflect the specific characteristics of a dataset.

Increasing plasma calprotectin (S100A8/A9) is associated with 12-month mortality and unfavourable functional outcome in critically ill COVID-19 patients

BackgroundCalprotectin (S100A8/A9) is a pro-inflammatory mediator primarily released from neutrophils. Previous studies have revealed associations between plasma calprotectin, disease severity and in-hospital mortality in unselected COVID-19 patients.ObjectiveWe aimed to assess whether plasma calprotectin dynamics during the first week of intensive care are associated with mortality and functional outcome in critically ill COVID-19 patients.MethodsThis prospective study included 498 COVID-19 patients admitted to six intensive care units (ICUs) in Sweden between May 2020 and May 2021. Blood samples were collected on ICU admission and on day 7. The primary outcome was 12-month mortality. Secondary outcomes were functional outcome of survivors at 3 and 12 months, and the need for invasive mechanical ventilation (IMV) or continuous renal replacement therapy (CRRT) during the ICU stay. Functional outcome was assessed by the Glasgow Outcome Scale Extended (GOSE, range 1–8, with < 5 representing an unfavourable outcome). Associations between plasma calprotectin and outcomes were examined in binary logistic regression analyses adjusted for age, sex, BMI, hypertension, smoking, and creatinine.ResultsHigh plasma calprotectin on admission and day 7 was independently associated with increased 12-month mortality. Increasing calprotectin from admission to day 7 was independently associated with higher mortality at 12 months [OR 2.10 (95% CI 1.18–3.74), p = 0.012], unfavourable functional outcome at 3 months [OR 2.53 (95% CI 1.07–6.10), p = 0.036], and the use of IMV [OR 2.23 (95% CI 1.10–4.53), p = 0.027)] and CRRT [OR 2.07 (95% CI 1.07–4.00), p = 0.031)]. A receiver operator characteristic (ROC) model including day 7 calprotectin and age was a good predictor of 12-month mortality [AUC 0.79 (95% CI 0.74–0.84), p < 0.001]. Day 7 calprotectin alone predicted an unfavourable functional outcome at 3 months [AUC 0.67 (95% CI 0.58–0.76), p < 0.001].ConclusionIn critically ill COVID-19 patients, increasing calprotectin levels after admission to the ICU are associated with 12-month mortality and unfavourable functional outcome in survivors. Monitoring plasma calprotectin dynamics in the ICU may be considered to evaluate prognosis in critical COVID-19.Study registration: ClinicalTrials.gov Identifier: NCT04974775, registered April 28, 2020.

Longitudinal Assessment of Blood-Based Inflammatory, Neuromuscular, and Neurovascular Biomarker Profiles in Intensive Care Unit-Acquired Weakness: A Prospective Single-Center Cohort Study.

The diagnosis of intensive care unit (ICU)-acquired weakness (ICUAW) and critical illness neuromyopathy (CINM) is frequently hampered in the clinical routine. We evaluated a novel panel of blood-based inflammatory, neuromuscular, and neurovascular biomarkers as an alternative diagnostic approach for ICUAW and CINM. Patients admitted to the ICU with a Sequential Organ Failure Assessment score of ≥ 8 on 3 consecutive days within the first 5 days as well as healthy controls were enrolled. The Medical Research Council Sum Score (MRCSS) was calculated, and motor and sensory electroneurography (ENG) for assessment of peripheral nerve function were performed at days 3 and 10. ICUAW was defined by an MRCSS < 48 and CINM by pathological ENG alterations, both at day 10. Blood samples were taken at days 3, 10, and 17 for quantitative analysis of 18 different biomarkers (white blood cell count, C-reactive protein, procalcitonin, C-terminal agrin filament, fatty-acid-binding protein 3, growth and differentiation factor 15, syndecan 1, troponin I, interferon-γ, tumor necrosis factor-α, interleukin-1α [IL-1α], IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13, and monocyte chemoattractant protein 1). Results of the biomarker analysis were categorized according to the ICUAW and CINM status. Clinical outcome was assessed after 3 months. Between October 2016 and December 2018, 38 critically ill patients, grouped into ICUAW (18 with and 20 without) and CINM (18 with and 17 without), as well as ten healthy volunteers were included. Biomarkers were significantly elevated in critically ill patients compared to healthy controls and correlated with disease severity and 3-month outcome parameters. However, none of the biomarkers enabled discrimination of patients with and without neuromuscular impairment, irrespective of applied classification. Blood-based biomarkers are generally elevated in ICU patients but do not identify patients with ICUAW or CINM. ClinicalTrials.gov identifier: NCT02706314.

Treat-and-Extend Versus Pro re nata Regimens of Ranibizumab and Aflibercept in Neovascular Age-Related Macular Degeneration: A Comparative Study from Routine Clinical Practice.

Anti-vascular endothelial growth factor (VEGF) is generally given using pro re nata or "treat-and-extend" (T&E) regimens for neovascular age-related macular degeneration (nAMD). Randomized clinical trials have reported that T&E is superior to Pro re nata (PRN), but results from clinical trials may not always be replicated in clinical practice. Real-world data comparing T&E and PRN regimens for nAMD are limited. The objective of this work was to report 24-month outcomes of PRN versus T&E regimens for ranibizumab and aflibercept to treat nAMD in routine clinical practice. We conducted a retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project (FRB). Treatment-naïve eyes starting nAMD treatment with at least three injections using a T&E or PRN regimen were tracked by using the FRB. The primary outcome was the mean change in visual acuity (VA) measured by the number of letters read on a logarithm of the minimum angle of resolution chart at 2years versus baseline. The secondary outcome was the number of injections at 2years. From January 1, 2015 to January 31, 2019, 3313 eyes from 2948 patients with nAMD were included: 1243 eyes from 1065 patients were classified as PRN and 2070 eyes from 1935 patients started a T&E regimen. At 24months, patients on the T&E regimen experienced significantly greater mean (95% confidence interval) improvement in VA than those on PRN (+ 4.2 [3.1, 5.2] vs. + 1.3 [0.1, 2.6] letters; p < 0.001), with more injections (14.9 standard deviation(SD) 4.3) vs. 9.8(SD 4.3); p < 0.001). Eyes treated with a T&E regimen had better VA outcomes from VEGF inhibitors than eyes treated PRN. This large real-world data assessment supports previous data from randomized clinical trials that the T&E regimen delivers better outcomes than PRN.

A prospective cohort study regarding usability of serum RIPK3 as a biomarker in relation to early hematoma growth and neurological outcomes after acute intracerebral hemorrhage

ObjectiveThe receptor-interacting protein kinase 3 (RIPK3) is a pivotal component for triggering necroptosis. We intended to investigate predictive effects of serum RIPK3 levels on early hematoma growth (EHG) and poor neurological outcome after acute intracerebral hemorrhage (ICH). MethodsIn this prospective cohort study, 183 ICH patients and 100 controls were enrolled for measuring serum RIPK3 levels. National Institutes of Health Stroke Scale (NIHSS) and hematoma volume were recorded as the severity indicators. EHG and poststroke 6-month unfavorable outcome (modified Rankin Scale scores of 3–6) were registered as the two prognostic parameters. Multivariate analyses were implemented to discern relevance of serum RIPK3 to ICH severity and prognosis. ResultsSerum RIPK3 levels of patients, which were dramatically higher than those of controls, were independently related to NIHSS scores, hematoma volume, EHG, 6-month mRS scores and unfavorable outcome. Risks of EHG and unfavorable outcome were linearly pertinent to and efficiently discriminated by RIPK3 levels under restricted cubic spline and receiver operating characteristic curve respectively. RIPK3 levels nonsignificantly interacted with age, gender, hypertension, etc. Predictive ability of RIPK3 levels resembled those of NIHSS scores and hematoma volume. The prediction models, in which serum RIPK3, NIHSS scores and hematoma volume were integrated, were visually displayed via nomograms. The models’ predictive capabilities substantially surpassed that of serum RIPK3, NIHSS scores and hematoma volumes alone. The models kept stable under calibration curve. ConclusionA profound increase of serum RIPK3 levels after ICH is tightly relevant to severity, EHG and poor neurological outcomes, assuming that serum RIPK3 may emerge as a valuable prognostic predictor of ICH.

Incidence, risk factors, and impact of post-return of spontaneous circulation events in patients with out-of-hospital cardiac arrest: A population-based study in Tokyo, Japan

AimPatients with the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) are unstable and often experience rearrest, after which ROSC may be reattained. This study investigated the incidence and risk factors of post-ROSC events (rearrest and subsequent reattainment of ROSC) and their impact on outcomes in patients with prehospital ROSC following OHCA. MethodsPatients with OHCA and prehospital ROSC were identified from the Tokyo Fire Department database between 1 January 2018 and 31 December 2022. The factors associated with post-ROSC events and their impact on 1-month favourable neurological outcome (cerebral performance category scale: 1 or 2) were assessed using multivariable logistic regression analysis. ResultsOverall, 64,000 individuals experienced OHCA, and 6,190 (9.7%) had ROSC. Rearrest was confirmed in 28.4% of patients with ROSC, and was associated with age, time of emergency call, location of cardiac arrest, dispatcher instruction regarding cardiopulmonary resuscitation, first recorded cardiac rhythm, bystander cardiopulmonary resuscitation, defibrillation by a bystander, response time, and prehospital interventions. ROSC reattainment was confirmed in 34.5% of patients with rearrest and associated with the first recorded cardiac rhythm and defibrillation by a bystander. Patients without rearrests had the highest proportion of favourable neurological outcomes, followed by those with solved and unsolved rearrests (38.6% vs. 22.4% and 4.4%, P < 0.001). The difference remained significant after adjustment for confounders. ConclusionThis study revealed population-based incidence and risk factors of post-ROSC events. Rearrest was common, leading to unfavourable neurological outcome; however, its deleterious impact may be mitigated by successful resuscitation efforts.