Anaesthesia practice, quality indices including all-cause 30-day mortality associate to wrist fracture repositioning and surgery in Sweden: A perioperative register-based study 2018-2021.

BACKGROUND: Wrist fracture is one of most common fractures frequently requiring surgical anaesthesia. There is limited information related to the anaesthetic practice and quality including 30-day mortality associated with wrist fracture in Sweden in recent years. AIM: The aim of the present register-based study was to investigate the anaesthesia techniques used and quality indices including 30-day mortality associated with wrist fracture surgery in Sweden during the period 2018-2021. MATERIALS AND METHODS: All fracture repositions, and surgical interventions related to wrist fracture requiring anaesthesia in patients aged >18 years registered in the Swedish Perioperative Register (SPOR) between 2018 and 2021 were included in the analysis. Information on age, ASA class, anaesthesia technique, severe operative events, most reported side-effects during recovery room stay and all-cause 30-day mortality was collected. RESULTS: The data set included 25,147 procedures split into 14,796 females and 10,252 males (missing information n = 99) with a mean age of 52.9 ± 18.7 years and a significant age difference between females and males, 60.3 ± 15.4 and 42.2 ± 17.7 years, respectively. Mean age and ASA class increased during the study period (2018-2021), from 52.8 ± 18.6 to 54.0 ± 18.4 and ASA class 3-5 from 8.1% to 9.4% (p < .001 and p < .041, respectively). General anaesthesia (GA), GA combined with regional anaesthesia (RA), RA with or without sedation and sedation only was used in 41%, 13%, 40% and 6% of procedures, respectively, with minor changes over the study period. Pain at arrival in the recovery room (RR), (3.4%), severe pain during RR stay (2.1%), hypothermia (1.4%), postoperative nausea and vomiting (PONV) (1.2%) and urinary retention (0.5%) were the most reported side-effects during the RR stay. (RA) was associated with significantly lower occurrence of pain and PONV, and shorter RR stay, compared with GA (p < .001). The all-cause 30-day mortality was low (19 of 25,147 (0.08%)) with no differences over the period studied or anaesthetic technique. CONCLUSION: General anaesthesia or general anaesthesia combined with regional anaesthesia are the most used anaesthetic techniques for wrist fracture procedures in Sweden. Recovery room pain, PONV, hypothermia and urinary retention is reported in overall low frequencies, with no change over the period studied, but in lower frequencies for regional anaesthesia. All-cause 30-day mortality was low; 0.08% with no change over time or between anaesthetic techniques. Thus, the present quality review based on SPOR data supports high quality of perioperative anaesthesia care.

ICURE: Intensive care unit (ICU) risk evaluation for 30-day mortality. Developing and evaluating a multivariable machine learning prediction model for patients admitted to the general ICU in Sweden.

BACKGROUND: A prediction model that estimates mortality at admission to the intensive care unit (ICU) is of potential benefit to both patients and society. Logistic regression models like Simplified Acute Physiology Score 3 (SAPS 3) and APACHE are the traditional ICU mortality prediction models. With the emergence of machine learning (machine learning) and artificial intelligence, new possibilities arise to create prediction models that have the potential to sharpen predictive accuracy and reduce the likelihood of misclassification in the prediction of 30-day mortality. METHODS: We used the Swedish Intensive Care Registry (SIR) to identify and include all patients ≥18 years of age admitted to general ICUs in Sweden from 2008 to 2022 with SAPS 3 score registered. Only data collected within 1 h of ICU admission was used. We had 153 candidate predictors including baseline characteristics, previous medical conditions, blood works, physiological parameters, cause of admission, and initial treatment. We stratified the data randomly on the outcome variable 30-day mortality and created a training set (80% of data) and a test set (20% of data). We evaluated several hundred prediction models using multiple ML frameworks including random forest, gradient boosting, neural networks, and logistic regression models. Model performance was evaluated by comparing the receiver operator characteristic area under the curve (AUC-ROC). The best performing model was fine-tuned by optimizing hyperparameters. The model's calibration was evaluated by a calibration belt. Ultimately, we simplified the best performing model with the top 1-20 predictors. RESULTS: We included 296,344 first-time ICU admissions. We found age, Glasgow Coma Scale, creatinine, systolic blood pressure, and pH being the most important predictors. The AUC-ROC was 0.884 in test data using all predictors, specificity 95.2%, sensitivity 47.0%, negative predictive value of 87.9% and positive predictive value of 70.7%. The final model showed excellent calibration. The ICU risk evaluation for 30-day mortality (ICURE) prediction model performed equally well to the SAPS 3 score with only eight variables and improved further with the addition of more variables. CONCLUSION: The ICURE prediction model predicts 30-day mortality rate at first-time ICU admission superiorly compared to the established SAPS 3 score.

Progressive changes in pulmonary gas exchange during invasive respiratory support for COVID-19 associated acute respiratory failure: A retrospective study of the association with 90-day mortality.

BACKGROUND: Ratio of arterial pressure of oxygen and fraction of inspired oxygen (P/F ratio) together with the fractional dead space (Vd/Vt) provides a global assessment of pulmonary gas exchange. The aim of this study was to assess the potential value of these variables to prognosticate 90-day survival in patients with COVID-19 associated ARDS admitted to the Intensive Care Unit (ICU) for invasive ventilatory support. METHODS: In this single-center observational, retrospective study, P/F ratios and Vd/Vt were assessed up to 4 weeks after ICU-admission. Measurements from the first 2 weeks were used to evaluate the predictive value of P/F ratio and Vd/Vt for 90-day mortality and reported by the adjusted hazard ratio (HR) and 95% confidence intervals [95%CI] by Cox proportional hazard regression. RESULTS: Almost 20,000 blood gases in 130 patients were analyzed. The overall 90-day mortality was 30% and using the data from the first ICU week, the HR was 0.85 [0.77-0.94] for every 10 mmHg increase in P/F ratio and 1.61 [1.20-2.16] for every 0.1 increase in Vd/Vt. In the second week, the HR for 90-day mortality was 0.82 [0.75-0.89] for every 10 mmHg increase in P/F ratio and 1.97 [1.42-2.73] for every 0.1 increase in Vd/Vt. CONCLUSION: The progressive changes in P/F ratio and Vd/Vt in the first 2 weeks of invasive ventilatory support for COVID-19 ARDS were significant predictors for 90-day mortality.

Acute-Phase Neurofilament Light and Glial Fibrillary Acidic Proteins in Cerebrospinal Fluid Predict Long-Term Outcome After Severe Traumatic Brain Injury.

BACKGROUND: This study investigated trajectory profiles and the association of concentrations of the biomarkers neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in ventricular cerebrospinal fluid (CSF) with clinical outcome at 1 year and 10-15 years after a severe traumatic brain injury (sTBI). METHODS: This study included patients with sTBI at the Neurointensive Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. The injury was regarded as severe if patients had a Glasgow Coma Scale ≤ 8 corresponding to Reaction Level Scale ≥ 4. CSF was collected from a ventricular catheter during a 2-week period. Concentrations of NfL and GFAP in CSF were analyzed with enzyme-linked immunosorbent assay. The Glasgow Outcome Scale (GOS) was used to assess the 1-year and 10-15-year outcomes. After adjustment for age and previous neurological diseases, logistic regression was performed for the outcomes GOS 1 (dead) or GOS 2-5 (alive) and GOS 1-3 (poor) or GOS 4-5 (good) versus the independent continuous variables (NfL and GFAP). RESULTS: Fifty-three patients with sTBI were investigated; forty-seven adults are presented in the article, and six children (aged 7-18 years) are described in Supplement 1. The CSF concentrations of NfL gradually increased over 2 weeks post trauma, whereas GFAP concentrations peaked on days 3-4. Increasing NfL and GFAP CSF concentrations increased the odds of GOS 1-3 outcome 1 year after trauma (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.07-2.80, p = 0.025; and OR 1.61, 95% CI 1.09-2.37, p = 0.016, respectively). Similarly, increasing CSF concentrations of NfL and GFAP increased the odds for GOS 1-3 outcome 10-15 years after trauma (OR 2.04, 95% CI 1.05-3.96, p = 0.035; and OR 1.60, 95% CI 1.02-2.00, p = 0.040). CONCLUSIONS: This study shows that initial high concentrations of NfL and GFAP in CSF are both associated with higher odds for GOS 1-3 outcome 1 year and 10-15 years after an sTBI, implicating its potential usage as a prognostic marker in the future.

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction are Altered in Parkinson's Disease and Related Disorders.

BACKGROUND: Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects. OBJECTIVE: To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders. METHODS: Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n1  = 51, n2  = 101), corticobasal degeneration (CBD) (n1  = 11, n2  = 3), progressive supranuclear palsy (PSP) (n1  = 22, n2  = 21), multiple system atrophy (MSA) (n1  = 31, n2  = 26), and healthy control (HC) (n1  = 48, n2  = 30) participants, as well as Alzheimer's disease (AD) (n2  = 23) patients in the second cohort. RESULTS: Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25-0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; ß-estimate = -0.025 to -0.038, P < 0.05) and cognitive decline (NPTX2; ß-estimate = 0.32, P = 0.021). CONCLUSIONS: These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Presence of neural surface and onconeural autoantibodies in cerebrospinal fluid and serum in neurological diseases presents a potential risk for misdiagnosis.

BACKGROUND AND PURPOSE: Autoantibodies have been found to contribute to pathology and are used in the diagnosis of some neurological diseases. We examined the prevalence of autoantibodies in patients with various neurological diseases and whether patients who had autoantibodies differed in age, sex, or disability from those who did not. METHODS: We examined the prevalence of neural surface and onconeural autoantibodies in cerebrospinal fluid (CSF) and serum from patients with multiple sclerosis (n = 64), Parkinson disease plus atypical parkinsonism (n = 150), amyotrophic lateral sclerosis (n = 43), or autoimmune encephalitis (positive control; n = 7) and a healthy control group (n = 37). A total of 12 onconeural autoantibodies and six neural surface autoantibodies were tested in all participants. RESULTS: Autoantibodies were present in all cohorts. The prevalence of autoantibodies was high (>80%) in the autoimmune encephalitis cohort but low (<20%) in all other cohorts. When comparing patients within cohorts who were positive for autoantibodies to patients who were not, there was no difference in age, sex, and disability. This was apart from the multiple sclerosis and Parkinson disease plus atypical parkinsonism cohorts, where those with positivity for autoantibodies in the CSF were significantly older. CONCLUSIONS: The presence of the autoantibodies examined does not appear to have a substantial clinical impact within the diseases examined in this study. The presence of autoantibodies in all cohorts presents a risk for misdiagnosis when the method is used incorrectly on patients with atypical clinical presentation.

SCRN1: A cerebrospinal fluid biomarker correlating with tau in Alzheimer's disease.

INTRODUCTION: Secernin-1 (SCRN1) is a neuronal protein that co-localizes with neurofibrillary tangles in Alzheimer's disease (AD), but not with tau inclusions in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), or Pick's disease. METHODS: We measured SCRN1 concentration in cerebrospinal fluid (CSF) using a novel mass spectrometric parallel reaction monitoring method in three clinical cohorts comprising patients with neurochemically characterized AD (n = 25) and controls (n = 28), clinically diagnosed Parkinson's disease (PD; n = 38), multiple system atrophy (MSA; n = 31), PSP (n = 20), CBD (n = 8), healthy controls (n = 37), and neuropathology-confirmed AD (n = 47). RESULTS: CSF SCRN1 was significantly increased in AD (P < 0.01, fold change = 1.4) compared to controls (receiver operating characteristic area under the curve = 0.78) but not in CBD, PSP, PD, or MSA. CSF SCRN1 positively correlated with CSF total tau (R = 0.78, P = 1.1 × 10-13 ), phosphorylated tau181 (R = 0.64, P = 3.2 × 10-8 ), and Braak stage and negatively correlated with Mini-Mental State Examination score. DISCUSSION: CSF SCRN1 is a candidate biomarker of AD, reflecting tau pathology. HIGHLIGHTS: We developed a parallel reaction monitoring assay to measure secernin-1 (SCRN1) in cerebrospinal fluid (CSF). CSF SCRN1 was increased in Alzheimer's disease compared to healthy controls. CSF SCRN1 remained unchanged in Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, or corticobasal degeneration compared to controls. CSF SCRN1 correlated strongly with CSF phosphorylated tau and total tau. CSF SCRN1 increased across Braak stages and negatively correlated with Mini-Mental State Examination score.

Interactive Interventions Can Improve Hand Hygiene and Aseptic Techniques During Perioperative Care-Experience From the "Safe Hands" Project.

PURPOSE: This paper evaluates a theory-driven, interactive hand hygiene (HH) intervention, the Safe Hands project, based on theories of organizational learning and culture including leadership support, dialogue and co-creation. DESIGN: This prospective quasi-experimental study used unobtrusive overt observations to evaluate adherence to HH recommendations after implementing an infection-prevention intervention. METHODS: The primary outcome was differences in HH practices "Before aseptic/clean procedure" (WHO moment 2), "After body fluid exposure risk" (WHO moment 3) and performance of aseptic techniques. One operating room (OR) department served as the study hospital and the other as the control hospital, both at Swedish university hospitals. Adherence to HH guidelines was measured 4 times during 2015 to 2017. FINDINGS: The intervention site displayed a significant improvement in adherence to HH guidelines and aseptic techniques. WHO 2; from 23.8% to 36.2%, (P = .014), WHO 3; from 22.2% to 42.3%, (P = .002), and aseptic techniques; from 17.5% to 31.6%, (P = .003). No changes in adherence were identified at the control site. The use of contaminated gloves decreased post intervention at the study operating department. CONCLUSIONS: This study shows that implementing tailored interventions that are underpinned by theories from organizational learning and culture can improve adherence to hand hygiene in a complex setting as the OR up to 6 months post-intervention. The interprofessional co-creation of standards operating procedures addressing specific care procedures and emphasizing the importance of aseptic techniques can be an acceptable and feasible way to reduce the risks of contaminating medical devices and patients during perioperative care.

A co-created nurse-driven catheterisation protocol can reduce bladder distension in acute hip fracture patients - results from a longitudinal observational study.

BACKGROUND: Urinary retention is common in elderly patients undergoing acute hip fracture surgery. Avoiding overfilling the urinary bladder is important to avoid detrusor muscle damage and associated motility problems. The aim of this study was to analyse associations between the co-creation of a nurse-driven urinary catheterisation protocol and the incidence of bladder distension in patients undergoing hip fracture surgery. METHODS: This is a single-centre implementation intervention with a retrospective longitudinal observation design, using five measures points, spanning from June 2015 to March 2020. The intervention was theory driven and the participants, together with the facilitators and researcher, co-created a nurse-driven urinary catheterisation protocol. Data were retrieved from the hip fracture register. Uni- and multivariable logistic regressions were used for analyses of changes in bladder distension and urinary volume of ≥500 ml over the years. RESULTS: A total of 3078 patients were included over a five-year period. The implementation intervention was associated with a reduction in the proportion of patients with bladder distension of 31.5% (95% confidence interval 26.0-37.0), from year 1 to year 5. The multivariable analysis indicated a 39% yearly reduction in bladder distension, OR 0.61 (95% confidence interval 0.57-0.64, p <  0001). There was a reduction in the proportion of patients with a bladder volume of ≥500 ml of 42.8% (95% confidence interval 36.2-49.4), from year 1 to year 5. The multivariable analysis found a 41% yearly reduction in patients with a bladder volume of ≥500 ml, OR 0.59 (95% confidence interval 0.55-0.64, p <  0.0001). The intervention was associated with improved documentation of both catheter indications and removal plans. CONCLUSION: The use of predefined catheter indications and a tighter bladder scanning schedule were associated with a reduction in the incidence of both bladder distension and urine volume ≥ 500 ml in hip fracture patients. Registered nurses can play an active role in the facilitation of timely and appropriate catheter treatment in patients with hip fractures. TRIAL REGISTRATION: Clinical Trial Registry ISRCTN 17022695 registered retrospectively on 23 December 2021, in the end of the study, after data collection.

Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study.

OBJECTIVE: Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of ≥1.0 compared to patients without long-term cognitive decline at 3 months postsurgery. METHODS: Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. RESULTS: Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). INTERPRETATION: Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort. Ann Neurol 2020;87:370-382.

Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.

BACKGROUND: Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function. METHODS: In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid ß (Aß1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery. RESULTS: CSF and blood concentrations of T-tau, neurone-specific enolase, and Aß1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aß1-42. CONCLUSIONS: The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.

Validation of the Nottingham Hip Fracture Score (NHFS) for the prediction of 30-day mortality in a Swedish cohort of hip fractures.

BACKGROUND: Hip fracture is a common osteoporotic fracture with great morbidity and mortality. The utility of ASA classification is limited, as most patients are ≥ASA 3. A reliable predictor of mortality risk could support decision-making. We aimed to evaluate Nottingham hip fracture score (NHFS) for the prediction of 30-day mortality and then to recalibrate the formula converting NHFS to risk of 30-day mortality. METHODS: All patients >60 years with surgically treated hip fracture surgery during 2015-16 were assessed. Data was extracted manually from routinely collected clinical data in registry and medical records. Discriminative performance of NHFS and ASA was assessed with C-statistics. The conversion formula from NHFS to risk of 30-day mortality was recalibrated using logistic binominal regression. Observed vs expected ratios of 30-day mortality were compared with the 2012 NHFS-formula and recalibration was performed in a split dataset. RESULTS: 1864 patients were included, with 213 deaths within 30 days. C-statistic were 0.64 for NHFS and 0.62 for ASA. Comparing expected values from the 2012-revision with our observed deaths gave a ratio of 1.37. Relating predicted levels of 30-day mortality based on 70% of our cohort vs. 30% test portion of our Swedish dataset gave a ratio of 0.97. DISCUSSION: NHFS underestimated mortality in our cohort and showed poor discrimination. Revision of the formula based on a split dataset improved calibration. We suggest NHFS to be routinely implemented to support clinical judgements, expand preoperative assessment and escalate intraoperative monitoring.

Supraclavicular block with Mepivacaine vs Ropivacaine, their impact on postoperative pain: a prospective randomised study.

BACKGROUND: Supraclavicular block (SCB) with long-acting local anaesthetic is commonly used for surgical repair of distal radial fractures (DRF). Studies have shown a risk for rebound pain when the block fades. This randomised single-centre study aimed to compare pain and opioid consumption the first three days post-surgery between SCB-mepivacaine vs. SCB-ropivacaine, with general anaesthesia (GA) as control. METHODS: Patients (n = 90) with ASA physical status 1-3 were prospectively randomised to receive; SCB with mepivacine 1%, 25-30 ml (n = 30), SCB with ropivacaine 0.5%, 25-30 ml (n = 30) or GA (n = 30) with propofol/fentanyl/sevoflurane. Study objectives compared postoperative pain with Numeric Rating Scale (NRS) and sum postoperative Opioid Equivalent Consumption (OEC) during the first 3 days post-surgery between study-groups. RESULTS: The three groups showed significant differences in postoperative pain-profile. Mean NRS at 24 h was significantly lower for the SCB-mepivacaine group (p = 0.018). Further both median NRS and median OEC day 0 to 3 were significanly lower in the SCB-mepivacaine group as compared to the SCB-ropivacaine group during the first three days after surgery; pain NRS 1 (IQR 0.3-3.3) and 2.7 (IQR 1.3-4.2) (p = 0.017) and OEC 30 mg (IQR 10-80) and 85 mg (IQR 45-125) (p = 0.004), respectively. The GA-group was in between both in pain NRS and median sum OEC. Unplanned healthcare contacts were highest among SCB-ropivacaine patients (39.3%) vs. SCB-mepivacaine patients (0%) and GA-patients (3.4%). CONCLUSIONS: The potential benefit of longer duration of analgesia, associated to a long-acting local anaesthetic agent, during the early postoperative course must be put in perspective of potential worse pain progression following block resolution. TRIAL REGISTRATION: NCT03749174 (clinicaltrials.gov, Nov 21, 2018, retrospectively registered).

The influence of time-to-surgery on mortality after a hip fracture.

BACKGROUND: The effect of time-to-surgery on mortality in acute hip fracture (AHF) patients has been debated and studies are inconsistent regarding from what time limit mortality starts to increase. At Sahlgrenska University Hospital/Mölndal, surgery is recommended within 24 hours leaving little time for pre-operative optimization. However, internationally the definition of early surgery varies between 24 and 48 hours and over. This retrospective study was initiated to investigate the relation between time-to-surgery and 30-day mortality. METHOD: Data of AHF patients from January 2007 through December 2016 were collected. The variables analysed were: age, gender, American Society of Anesthesiologists physical status classification, surgical method (prosthesis or osteosynthesis) and time-to-surgery, along with 30-day mortality. Primary outcome was 30-day mortality related to time-to-surgery divided into groups. Secondary outcome was 30-day mortality related to time-to-surgery analysed hour-by-hour. RESULTS: From 10,844 eligible patients, 9,270 patients were included into the study. Mean time-to-surgery was 19.4 hours and overall 30-day mortality was 7.6%. Adjusted Cox regression analysis revealed an increased mortality rate in patients with time-to-surgery >48 hours. In the hour-by-hour analysis, significant mortality increase was observed at 39 hours of time-to-surgery. Patients with time-to-surgery >24 hours did not have increased mortality compared to patients with time-to-surgery <24 hours. CONCLUSION: In AHF patients, a time-to-surgery exceeding 39-48 hours was associated with increased mortality. Patients with surgeries performed before 39-48 hours did not have increased mortality and this time may, in some patients, be used for optimization prior surgery even if time-to-surgery exceeds 24 hours.

Dementia and CSF-biomarkers for Alzheimer's disease predict mortality after acute hip fracture.

BACKGROUND: Mortality is high after an acute hip fracture (AHF) surgery. Are cognitive impairment and/or altered levels of Alzheimer's Disease (AD)-biomarkers in cerebrospinal fluid (CSF) predictors of mortality in AHF-patients, as retrospective studies indicate? METHODS: Prospective single-center study including 373 AHF-patients, operated in spinal anesthesia. Cognitive status was evaluated by clinical dementia rating (CDR); CSF was analyzed for AD-biomarker concentrations (total tau (T-tau), phosphorylated tau (P-tau), amyloid beta ratio (Aß42/Aß40). CDR and biomarker levels were related to mortality up to one-year post-surgery, using univariate logistic regression analysis. RESULTS: Survival analyses showed that mortality was associated to the degree of dementia. In the entire patient cohort 30-, 90-, and 365-day mortality rates were 7.2%, 15.5%, and 25.5%, respectively, but only 2.7%, 5.5%, and 12.6%, for cognitively intact vs 16.3%, 31.7%, and 42.3% for demented patients (OR = 2.2-2.8 [CI = 1.6-4.9]; P = .0001). High CSF T-tau (OR = 1.19 [CI = 1.05-1.33]; P = .004) and low Aß42/Aß40-ratio (OR = 0.85 [CI = 0.74-0.97]; P = .017) were associated with increased 90-day mortality. Analysis of 4 subgroups (Cognitive impairment ± and Biomarkers ±) showed significant associations of dementia and CSF biomarker concentrations to mortality after an AHF. Even cognitively intact patients presenting with abnormal AD-biomarkers showed an increased 90-day mortality which, however, was statistically insignificant. CONCLUSIONS: Cognitive impairment and altered CSF biomarker concentrations indicative of AD pathology can predict increased mortality in patients with an AHF, and so probably even before clinical dementia diagnosis by early biomarker analysis; a notion that may have substantial clinical implications by improving perioperative treatment and postoperative rehabilitation.

The role of bone cement for the development of intraoperative hypotension and hypoxia and its impact on mortality in hemiarthroplasty for femoral neck fractures.

Background and purpose - The bone cement implantation syndrome characterized by hypotension and/or hypoxia is a well-known complication in cemented arthroplasty. We studied the incidence of hypotension and/or hypoxia in patients undergoing cemented or uncemented hemiarthroplasty for femoral neck fractures and evaluated whether bone cement was an independent risk factor for postoperative mortality.Patients and methods - In this retrospective cohort study, 1,095 patients from 2 hospitals undergoing hemiarthroplasty with (n = 986) and without (n = 109) bone cementation were included. Pre-, intra-, and postoperative data were obtained from electronic medical records. Each patient was classified for grade of hypotension and hypoxia during and after prosthesis insertion according to Donaldson's criteria (Grade 1, 2, 3). After adjustments for confounders, the hazard ratio (HR) for the use of bone cement on 1-year mortality was assessed.Results - The incidence of hypoxia and/or hypotension was higher in the cemented (28%) compared with the uncemented group (17%) (p = 0.003). The incidence of severe hypotension/hypoxia (grade 2 or 3) was 6.9% in the cemented, but not observed in the uncemented group. The use of bone cement was an independent risk factor for 1-year mortality (HR 1.9, 95% CI 1.3-2.7), when adjusted for confounders.Interpretation - The use of bone cement in hemiarthroplasty for femoral neck fractures increases the incidence of intraoperative hypoxia and/or hypotension and is an independent risk factor for postoperative 1-year mortality. Efforts should be made to identify patients at risk for BCIS and alternative strategies for the management of these patients should be considered.

Prolonged vasopressor support during hip-fracture surgery is a risk factor for enhanced mortality.

BACKGROUND: Hip fracture is a common injury in the elderly population and is associated with high morbidity and mortality. Intraoperative hypotension is commonly noted, and is often treated with vasopressors (VP), however, to what extent is unknown. We set out to examine retrospectively how many hip fracture-patients received VP perioperatively and further to investigate if VP treatment is connected to increased mortality. METHOD: Data on VP treatment were captured from medical and anaesthesia journals, and if so, data were investigated to find potential confounders. Patients were divided into (a) no VP, (b) VP by injection, (c) VP by infusion <3 hours, and (d) VP by infusion ≥3 hours to achieve stratification. RESULTS: Nine hundred and ninety-seven patients were included. About 80.4% received VP treatment. The 30-day mortality rates in subgroups were 3.6%, 5.4%, 6.4% and 19.1% respectively. The 90-day mortality rates were 6.7%, 10.3%, 11.6% and 30.3% respectively. Finally, the same patient groups had 365-day mortality rates of 12.8%, 20.0%, 23.3% and 44.9% respectively. We found a significant increase in mortality (30-90-365 days) in patients receiving VP infusion ≥3 hours, after adjusting for confounding factors. There was no increased mortality in patients treated by injection and by infusion <3 hours after adjustment for confounding factors vs untreated patients. CONCLUSION: Vasopressor treatment is common during hip fracture surgery. Patients treated with VP infusion ≥3 hours have increased mortality, while patients treated with injections or infusion <3 hours have not. We suggest that the prolonged use of VP treatment is linked to increased mortality.

Pulmonary haemodynamics and right ventricular function in cemented vs uncemented total hip arthroplasty-A randomized trial.

BACKGROUND: Bone cement implantation syndrome (BCIS) is a feared complication in orthopaedic surgery with a huge impact on post-operative morbidity. In this randomized trial, we evaluated the effects of bone cement on pulmonary and systemic haemodynamics in patients receiving either cemented or uncemented hip arthroplasty for isolated femoral neck fracture. METHODS: Twenty-two patients were randomized to receive either cemented (n = 10) or uncemented (n = 12) total hip arthroplasty. Surgery was performed under total intravenous anaesthesia in the lateral position. All patients were catheterized with radial- and pulmonary artery catheters, for continuous measurements of mean arterial pressure (MAP), pulmonary arterial pressure (PAP), cardiac output, right ventricular (RV) end-diastolic volume (RVEDV) and RV ejection fraction (RVEF). Haemodynamic measurements and blood gas analyses were performed after induction of anaesthesia, during surgery before and immediately after bone cementation and prosthesis insertion, 10 and 20 minutes after insertion and during skin closure. RESULTS: Pulmonary vascular resistance index (PVRI) increased during and after prosthesis insertion by 45% and 20% in the cemented and uncemented group, respectively (P < 0.005). Systolic and mean PAP increased by 18% and 17% in the cemented group, which was not seen in the uncemented group (P < 0.001). There was a trend for a more pronounced fall in RVEF in the cemented group, while there were no differences in cardiac output or stroke volume between groups. CONCLUSION: The use of bone cement in total hip arthroplasty increases pulmonary vascular resistance and the afterload of the RV with potentially negative effects on RV performance.

Inhaled prostacyclin for the prevention of increased pulmonary vascular resistance in cemented hip hemiarthroplasty-A randomised trial.

BACKGROUND: Bone cementation may cause pulmonary vasoconstriction and ventilation/perfusion abnormalities in patients undergoing cemented hip hemiarthroplasty. In this randomised trial, we tested the hypothesis that intra-operative inhalation of prostacyclin could attenuate the increase in pulmonary vascular resistance index (PVRI, primary endpoint) when compared to inhaled saline in this group of patients. METHODS: Twenty-two patients with displaced femoral neck fractures were allocated to receive inhaled aerosolised prostacyclin (20 ng/kg/min) (n = 11) or inhaled saline (NaCl, 9 mg/mL) (n = 11). All patients received total intravenous anaesthesia and were catheterised with radial and pulmonary artery fast response thermodilution catheters, for measurements of arterial and pulmonary arterial pressures, cardiac output, right ventricular ejection fraction and effective pulmonary arterial elastance. Haemodynamic measurements were performed after induction of anaesthesia, during surgery before and immediately after bone cementation and prosthesis insertion, 10 and 20 min after insertion and during skin closure. RESULTS: During the surgical procedure, PVRI increased both in the saline (44%, P < 0.001) and the prostacyclin (36%, P = 0.019) groups, with a less pronounced increase in the prostacyclin group (P = 0.031). Effective pulmonary arterial elastance increased both in the saline (44%, P < 0.001) and the prostacyclin groups (29%, P = 0.032), with a trend for a less pronounced increase in the prostacyclin group (P = 0.084). Right ventricular ejection fraction decreased significantly in both groups with no difference between the groups. CONCLUSION: Inhalation of prostacyclin attenuates the increase in pulmonary vascular resistance in patients undergoing cemented hip hemiarthroplasty and could potentially attenuate/prevent haemodynamic instability induced by an increase in right ventricular afterload seen in this procedure.

Identification of tissue-specific cell death using methylation patterns of circulating DNA.

Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic ß-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.