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Ischaemic brain infarction can occur without acute neurological symptoms (covert strokes) or with symptoms (overt strokes), both associated with poor health outcomes. We conducted a pilot study of the incidence of preoperative and postoperative (intraoperative or postoperative) covert strokes, and explored the relationship of postoperative ischaemic brain injury to blood levels of neurofilament light, a biomarker of neuronal damage.We analysed 101 preoperative (within 2 weeks of surgery) and 58 postoperative research MRIs on postoperative days 2-9 from two prospective cohorts collected at the University of Wisconsin (NCT01980511 and NCT03124303). Participants were aged65 yr and undergoing non-intracranial, non-carotid surgery.Preoperative covert stroke was identified in 2/101 participants (2%; Bayesian 95% confidence interval [CI], 0.2-5.4). This rate was statistically different from the postoperative ischaemic brain injury rate of 7/58 (12%, 4.9-21.3%; P=0.01) based on postoperative imaging. However, in a smaller group of participants with paired imaging (n=30), we did not identify the same effect (P=0.67). Patients with postoperative brain injury had elevated peak neurofilament light levels (median [inter-quartile range], 2.34 [2.24-2.64] logAlthough limited by a small sample size, these data suggest that preoperative covert stroke occurs more commonly than previously anticipated. Plasma neurofilament light is a potential screening biomarker for postoperative ischaemic brain injury.

Recent randomised controlled trials have failed to show a benefit in mortality by using processed electroencephalography (pEEG) to guide lighter anaesthesia. We performed a meta-analysis of mortality data from randomised trials of pEEG monitoring to assess the evidence of any protective effect of pEEG-guided light anaesthesia compared with deep anaesthesia in adults aged ≥18 yr.Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. In February 2022, we searched three databases (Cochrane CENTRAL, OVID Medline, EMBASE) for RCTs of pEEG monitoring that provided mortality data at 30 days, 90 days, and/or 1 yr or longer.We included 16 articles from 12 RCTs with 48 827 total participants. We observed no statistically significant mortality reduction with light anaesthesia compared with deep anaesthesia in patients aged ≥18 yr when all studies were pooled (odds ratio [OR]=0.99; 95% confidence interval (CI), 0.92-1.08). This result did not change significantly when analysing mortality at 30 days, 90 days, 1 yr or longer. We observed no mortality benefit for pEEG monitoring compared with usual care (OR=1.02; 95% CI, 0.89-1.18), targeting higher pEEG index values compared with lower values (OR=0.89; 95% CI, 0.60-1.32), or low pEEG index value alerts compared with no alerts (OR=1.02; 95% CI, 0.41-2.52).pEEG-guided lighter anaesthesia does not appear to reduce the risk of postoperative mortality. The absence of a plausible rationale for why deeper anaesthesia should increase mortality has hampered appropriate design of definitive clinical trials.CRD42022285195 (PROSPERO).

Case-control studies have associated delirium with blood-brain barrier (BBB) permeability. However, this approach cannot determine whether delirium is attributable to high pre-existing permeability or to perioperative changes. We tested whether perioperative changes in cerebrospinal fluid/plasma albumin ratio (CPAR) and plasma S100B were associated with delirium severity.Participants were recruited to two prospective cohort studies of non-intracranial surgery (NCT01980511, NCT03124303, and NCT02926417). Delirium severity was assessed using the Delirium Rating Scale-98. Delirium incidence was diagnosed with the 3D-Confusion Assessment Method (3D-CAM) or CAM-ICU (CAM for the ICU). CSF samples from 25 patients and plasma from 78 patients were analysed for albumin and S100B. We tested associations between change in CPAR (n=11) and S100B (n=61) and delirium, blood loss, CSF interleukin-6 (IL-6), and CSF lactate.The perioperative increase in CPAR and S100B correlated with delirium severity (CPAR ρ=0.78, P=0.01; S100B ρ=0.41, P0.001), delirium incidence (CPAR P=0.012; S100B P0.001) and CSF IL-6 (CPAR ρ=0.66 P=0.04; S100B ρ=0.75, P=0.025). Linear mixed-effect analysis also showed that decreased levels of S100B predicted recovery from delirium symptoms (P=0.001). Linear regression demonstrated that change in plasma S100B was independently associated with surgical risk, cardiovascular surgery, blood loss, and hypotension. Blood loss also correlated with CPAR (ρ=0.64, P=0.04), S100B (ρ=0.70, P0.001), CSF lactate (R=0.81, P=0.01), and peak delirium severity (ρ=0.36, P=0.01).Postoperative delirium is associated with a breakdown in the BBB. This increased permeability is dynamic and associated with a neuroinflammatory and lactate response. Strategies to mitigate blood loss may protect the BBB.

Supplementary Figures S1 to S5

Purpose:Report relevance of molecular groups to clinicopathologic features, germline SMARCB1/SMARCA4 alterations (GLA), and survival of children with atypical teratoid rhabdoid tumor (ATRT) treated in two multi-institutional clinical trials.Materials and Methods:Seventy-four participants with newly diagnosed ATRT were treated in two trials: infants (SJYC07: age < 3 years; n = 52) and children (SJMB03: age 3–21 years; n = 22), using surgery, conventional chemotherapy (infants), or dose-dense chemotherapy with autologous stem cell rescue (children), and age- and risk-adapted radiotherapy [focal (infants) and craniospinal (CSI; children)]. Molecular groups ATRT-MYC (MYC), ATRT-SHH (SHH), and ATRT-TYR (TYR) were determined from tumor DNA methylation profiles.Results:Twenty-four participants (32%) were alive at time of analysis at a median follow-up of 8.4 years (range, 3.1–14.1 years). Methylation profiling classified 64 ATRTs as TYR (n = 21), SHH (n = 30), and MYC (n = 13), SHH group being associated with metastatic disease. Among infants, TYR group had the best overall survival (OS; P = 0.02). However, outcomes did not differ by molecular groups among infants with nonmetastatic (M0) disease. Children with M0 disease and 2 residual tumor had a 5-year progression-free survival (PFS) of 72.7 ± 12.7% and OS of 81.8 ± 11%. Infants with M0 disease had a 5-year PFS of 39.1 ± 11.5% and OS of 51.8 ± 12%. Those with metastases fared poorly [5-year OS 25 ± 12.5% (children) and 0% (infants)]. SMARCB1 GLAs were not associated with PFS.Conclusions:Among infants, those with ATRT-TYR had the best OS. ATRT-SHH was associated with metastases and consequently with inferior outcomes. Children with nonmetastatic ATRT benefit from postoperative CSI and adjuvant chemotherapy.

Germline methodology

BackgroundAccumulating evidence supports sex differences in pharmacodynamic and pharmacokinetic drug profiles. However, recommended anaesthetic drug doses are not sex-adjusted, likely due to limited studies comparing sexes. Our objective was to systematically synthesise studies of anaesthetic key performance indicators (anaesthesia awareness), and markers of relatively lighter anaesthesia, time to emergence and dosing to achieve adequate depth of anaesthesia, for females and males.MethodsMEDLINE, Embase, and the Cochrane library databases. Studies were identified from inception of database to August 2nd, 2022. Controlled clinical trials (randomised and non-randomised) and prospective cohort studies that reported outcomes by sex for awareness with post-operative recall, connected consciousness during anaesthesia, depth of anaesthesia, and emergence from anaesthesia. Two authors undertook search, review, selection, and data abstraction. Risk of bias was assessed using the Newcastle Ottawa Scale. Results were synthesized by random effects meta-analysis where possible, or narrative form. Results were expressed as odds ratios (ORs) and mean differences (MDs) with corresponding 95% confidence intervals (CIs).ResultsOf the 19,749 studies identified from literature search, 66 citations of 64 studies (98,243 participants; 53,143 females and 45,100 males) were eligible for inclusion, of which 44 contributed to meta-analysis. Females had a higher incidence of awareness with post-operative recall (33 studies, OR 1.37, 95%CI 1.09 to 1.75) and connected consciousness during anaesthesia (3 studies, OR 2.09, 95% CI 1.04 to 4.23) than males. Time to emergence was faster in females than in males, including time to eye-opening (10 studies, MD -2.28 min, 95% CI -3.58 to -0.98), and time to response to command (6 studies, MD - 2.84 min, 95% CI -4.07 to -1.62). Data on depth of anaesthesia were heterogenous limiting synthesis to a qualitative review which did not identify differences by sex.ConclusionFemale sex was associated with a greater incidence of anaesthetic awareness, as well as faster emergence from anaesthesia. These data suggest reappraisal of anaesthetic care, including whether similar drug dosing for females and males represents best care. Equitable outcomes for females undergoing general anaesthesia warrants strategic focus in future research.Systematic review registrationPROSPERO CRD42022336087.

Despite many studies of potential delirium biomarkers, delirium pathophysiology remains unclear. Evidence shows that the quality of reporting delirium biomarker studies is sub-optimal. Better reporting of delirium biomarker studies is needed to understand delirium pathophysiology better. To improve robustness, transparency and uniformity of delirium biomarker study reports, the REDEEMS (Reporting Essentials for DElirium bioMarker Studies) guideline was developed by an international group of delirium researchers through a three-stage process, including a systematic review, a three-round Delphi study, and a follow-up consensus meeting. This process resulted in a 9-item guideline to inform delirium fluid biomarker studies. To enhance implementation of the REDEEMS guideline, this Explanation and Elaboration paper provides a detailed explanation of each item. We anticipate that the REDEEMS guideline will help to accelerate our understanding of delirium pathophysiology by improving the reporting of delirium biomarker research and, consequently the capacity to synthesise results across studies.

This scientific commentary refers to ‘Extremes of baseline cognitive function determine the severity of delirium: a population study’ by Tsui et al. (https://doi.org/10.1093/brain/awad062).

Study DesignRetrospective cohort studyObjectivesTo investigate the effect of perioperative gabapentin administration on postoperative pain and opioid use in elderly patients after elective posterior lumbar fusion.MethodsThis was a single-center study of patients over the age of 65 who underwent elective posterior lumbar fusion. The cohort was stratified into two groups based on perioperative gabapentin administration defined as use both in the immediate preoperative period and postoperatively during hospitalization. Mean daily visual analogue scale (VAS) pain scores and mean daily morphine equivalent dosage (MED) during the postoperative hospital stay were compared between these groups using traditional regression and inverse probability weighting.ResultsThere were 350 patients who received gabapentin perioperatively and 78 patients who did not receive gabapentin. Multivariate regression did not demonstrate a difference in daily MED (ß=-6.6 mg, p=0.816) or daily pain scores (ß=0.04, p=0.257) averaged over the first seven postoperative days. Sub-analysis stratifying by each individual postoperative day also did not demonstrate a difference in MED or pain scores.ConclusionThis study did not find perioperative gabapentin administration to be beneficial in reducing postoperative VAS pain scores or opioid use in the acute postoperative period for elderly patients undergoing posterior lumbar fusion. These findings are consistent with recent literature suggesting gabapentin is of minimal benefit in postoperative multimodal analgesia regimens.Level of Evidence3

Over the past two decades, the U.S. Geological Survey (USGS) National Earthquake Information Center (NEIC) has overcome many operational challenges. These range from minor disruptions, such as power outages, to significant operational changes, including system reconfiguration to handle unique earthquake sequences and the need to handle distributed work during a pandemic. Our ability to overcome crises is built on the development and implementation of a continuity of operations plan, well-designed infrastructure, adaptive software systems, experienced staff, and extensive collaboration. The NEIC does not operate in a vacuum but benefits from contributions of United States and international seismic networks. Similarly, the overall resilience of earthquake monitoring in the United States and around the globe benefits from the NEIC’s role as the national center for the Advanced National Seismic System (ANSS). Here, we highlight significant adaptations the NEIC has made in the face of crises. We discuss the COVID-19 pandemic, which represents the most significant operational crisis to impact the NEIC. The NEIC has maintained continuous operations during the ongoing COVID-19 pandemic by shifting from a fully onsite operations center to a distributed hybrid of onsite and telework staffing. We then discuss cases in which the NEIC has supported regional monitoring in the face of significant crises. In 2018, the NEIC assisted the Hawaiian Volcano Observatory with the Kīlauea volcano eruption by responding to large events, implementing contingency monitoring procedures, and calculating moment magnitudes for the low-frequency caldera collapses. Impacts of a crisis extend beyond the immediate response and often require a significant postevent assessment and a rebuilding phase. After the 2017 Hurricane Maria, the NEIC, the USGS National Strong-Motion Program, and the USGS Albuquerque Seismological Laboratory worked with the Puerto Rico Seismic Network and the Puerto Rico Strong-Motion program to assess, plan, and implement upgrades at sites that experienced storm damage.

BACKGROUND: Myocardial and neuronal injury occur commonly after noncardiac surgery. We examined whether patients who had perioperative myocardial injury (PMI) also incurred neuronal injury, and whether myocardial and neuronal injury were associated with similar changes in inflammatory markers or overlapping clinical predictors. METHODS: A total of 114 individuals >65 yr old were recruited from two ongoing perioperative cohort studies (NCT02926417; NCT03124303). Plasma samples were collected before and daily after surgery to process assays for troponin I (PMI), neurofilament light (NfL; neuronal injury) and multiplexed plasma cytokines (inflammation). The primary outcome was the change in NfL in individuals with PMI (>40 pg ml(−1) increase in troponin above preoperative values). We conducted logistic regression to identify if there were shared clinical predictors for myocardial and neuronal injury. RESULTS: Ninety-six patients had paired NfL and troponin data. Twenty-three of 94 subjects (24%) with PMI had greater increases in NfL (median [inter-quartile range, IQR]: 29 pg ml(−1) [3–95 pg ml(−1)]; 2.8-fold increase) compared with subjects with no troponin increase (8 pg ml(−1) [3–20]; 1.3-fold increase; P=0.008). PMI was associated with increased interleukin (IL)-1ra (P=0.005), IL-2 (P=0.045), IL-8 (P=0.002), and IL-10 (P

Purpose: Report relevance of molecular groups to clinicopathologic features, germline SMARCB1/SMARCA4 alterations (GLA), and survival of children with atypical teratoid rhabdoid tumor (ATRT) treated in two multi-institutional clinical trials. Materials and Methods: Seventy-four participants with newly diagnosed ATRT were treated in two trials: infants (SJYC07: age < 3 years; n = 52) and children (SJMB03: age 3–21 years; n = 22), using surgery, conventional chemotherapy (infants), or dose-dense chemotherapy with autologous stem cell rescue (children), and age- and risk-adapted radiotherapy [focal (infants) and craniospinal (CSI; children)]. Molecular groups ATRT-MYC (MYC), ATRT-SHH (SHH), and ATRT-TYR (TYR) were determined from tumor DNA methylation profiles. Results: Twenty-four participants (32%) were alive at time of analysis at a median follow-up of 8.4 years (range, 3.1–14.1 years). Methylation profiling classified 64 ATRTs as TYR (n = 21), SHH (n = 30), and MYC (n = 13), SHH group being associated with metastatic disease. Among infants, TYR group had the best overall survival (OS; P = 0.02). However, outcomes did not differ by molecular groups among infants with nonmetastatic (M0) disease. Children with M0 disease and Conclusions: Among infants, those with ATRT-TYR had the best OS. ATRT-SHH was associated with metastases and consequently with inferior outcomes. Children with nonmetastatic ATRT benefit from postoperative CSI and adjuvant chemotherapy.

Recent trials are conflicting as to whether titration of anaesthetic dose using electroencephalography monitoring reduces postoperative delirium. Titration to anaesthetic dose itself might yield clearer conclusions. We analysed our observational cohort to clarify both dose ranges for trials of anaesthetic dose and biological plausibility of anaesthetic dose influencing delirium.We analysed the use of sevoflurane in an ongoing prospective cohort of non-intracranial surgery. Of 167 participants, 118 received sevoflurane and were aged65 yr. We tested associations between age-adjusted median sevoflurane (AMS) minimum alveolar concentration fraction or area under the sevoflurane time×dose curve (AUC-S) and delirium severity (Delirium Rating Scale-98). Delirium incidence was measured with 3-minute Diagnostic Confusion Assessment Method (3D-CAM) or CAM-ICU. Associations with previously identified delirium biomarkers (interleukin-8, neurofilament light, total tau, or S100B) were tested.Delirium severity did not correlate with AMS (Spearman's ρ=-0.014, P=0.89) or AUC-S (ρ=0.093, P=0.35), nor did delirium incidence (AMS Wilcoxon P=0.86, AUC-S P=0.78). Further sensitivity analyses including propofol dose also demonstrated no relationship. Linear regression confirmed no association for AMS in unadjusted (log (IRR)=-0.06 P=0.645) or adjusted models (log (IRR)=-0.0454, P=0.735). No association was observed for AUC-S in unadjusted (log (IRR)=0.00, P=0.054) or adjusted models (log (IRR)=0.00, P=0.832). No association of anaesthetic dose with delirium biomarkers was identified (P0.05).Sevoflurane dose was not associated with delirium severity or incidence. Other biological mechanisms of delirium, such as inflammation and neuronal injury, appear more plausible than dose of sevoflurane.NCT03124303, NCT01980511.

BACKGROUND: Postoperative delirium is associated with increases in the neuronal injury biomarker, neurofilament light (NfL). Here we tested whether two other biomarkers, glial fibrillary acidic protein (GFAP) and tau, are associated with postoperative delirium. METHODS: A total of 114 surgical patients were recruited into two prospective biomarker cohort studies with assessment of delirium severity and incidence. Plasma samples were sent for biomarker analysis including tau, NfL, and GFAP, and a panel of 10 cytokines. We determined a priori to adjust for interleukin-8 (IL-8), a marker of inflammation, when assessing associations between biomarkers and delirium incidence and severity. RESULTS: GFAP concentrations showed no relationship to delirium. The change in tau from preoperative concentrations to postoperative Day 1 was greater in patients with postoperative delirium (P

Requirements for the undergraduate major in Hispanic literature and offerings of Spanish peninsular and Latin American literature courses surveying the canon, masterpieces, major works, major authors, major trends, or representative works at fifty-six selected US colleges and universities were examined for academic years 1990–91, 2002–03, 2013–14, and 2017–18. The number of literature survey courses at these institutions decreased during this 27-year period, as did the number of schools requiring such courses. The composition of the literature survey courses also changed, most notably to incorporate other cultural products and approaches.

A 6-month-old, neutered male, Vietnamese potbellied pig presented for evaluation of exercise intolerance and intermittent episodes of exertional cyanosis. Initial diagnostic evaluation revealed arterial hypoxemia. Transthoracic echocardiogram revealed double-outlet right ventricle (DORV) and a subaortic ventricular septal defect. Agitated saline contrast study confirmed the entry of saline contrast from the right ventricle into both pulmonary artery and aorta. Due to deterioration of clinical status, the patient was euthanized 3 months later. Gross necropsy examination was performed confirming the congenital cardiac defects noted on the echocardiogram. To the authors knowledge, this is the first case report of DORV in a Vietnamese potbellied pig.

Background The primary objective of this study is to evaluate the peri-procedural major and minor complications associated with percutaneous femoral arterial access using modified Seldinger’s technique in dogs that underwent cardiac catheterization. Methods Medical records of 62 client owned dogs that underwent percutaneous femoral arterial access for interventional cardiac procedures were retrospectively evaluated. Post-procedural manual compression was used for hemostasis. Peri-procedural vascular access complications (that occurred from procedure time to discharge) were evaluated. Vascular access complications were divided into two groups: minor complications that did not require specific therapy and major complications that did require an intervention to address the complication associated with vascular access. Results The minor complication rate was 30.6% (19/62) with most dogs experiencing minor bruising and small hematomas. The major complication rate was 3.2% (2/62). Both major complications were associated with bleeding with one dog requiring blood transfusion and the other dog requiring fluid therapy. No peri-procedural mortality associated with vascular access was noted. Conclusion This retrospective study suggests that percutaneous femoral arterial access using the modified Seldinger’s technique with post-procedural manual compression for hemostasis is viable option for vascular access during cardiac catheterization and associated with no peri-procedural mortality in dogs. The lower rate of complications noted in this study may be related to operator experiences and as such complication rate at a single center may not reflect the experience at other centers.

A 3-year-old, male neutered, domestic short-haired cat presented for evaluation of respiratory distress. Transthoracic echocardiography revealed a left-to-right shunting ventricular septal defect, a left-to-right shunting patent ductus arteriosus, and a vegetative growth on the aortic valve leaflet consistent with aortic valve endocarditis. Because of poor response to therapy, the owner elected euthanasia, and a necropsy was performed. Gross necropsy examination confirmed the congenital cardiac defects, and aortic valve endocarditis was noted on the echocardiogram. Histopathological examination revealed diffuse interstitial pneumonia and evidence for systemic septic embolism including renal infarcts and brain microabscesses. To the authors' knowledge, this is the first case report of aortic valve endocarditis in a cat in association with congenital cardiac malformations.