Identification of intracellular bacteria from multiple single-cell RNA-seq platforms using CSI-Microbes.

The study of the tumor microbiome has been garnering increased attention. We developed a computational pipeline (CSI-Microbes) for identifying microbial reads from single-cell RNA sequencing (scRNA-seq) data and for analyzing differential abundance of taxa. Using a series of controlled experiments and analyses, we performed the first systematic evaluation of the efficacy of recovering microbial unique molecular identifiers by multiple scRNA-seq technologies, which identified the newer 10x chemistries (3' v3 and 5') as the best suited approach. We analyzed patient esophageal and colorectal carcinomas and found that reads from distinct genera tend to co-occur in the same host cells, testifying to possible intracellular polymicrobial interactions. Microbial reads are disproportionately abundant within myeloid cells that up-regulate proinflammatory cytokines like IL1Β and CXCL8, while infected tumor cells up-regulate antigen processing and presentation pathways. These results show that myeloid cells with bacteria engulfed are a major source of bacterial RNA within the tumor microenvironment (TME) and may inflame the TME and influence immunotherapy response.

A comparative cohort study of surgical approaches for adult spinal deformity at a minimum 2-year follow-up.

STUDY DESIGN: This study was a retrospective multi-center comparative cohort study. MATERIALS AND METHODS: A retrospective institutional database of operative adult spinal deformity patients was utilized. All fusions > 5 vertebral levels and including the sacrum/pelvis were eligible for inclusion. Revisions, 3 column osteotomies, and patients with < 2-year clinical follow-up were excluded. Patients were separated into 3 groups based on surgical approach: 1) posterior spinal fusion without interbody (PSF), 2) PSF with interbody (PSF-IB), and 3) anteroposterior (AP) fusion (anterior lumbar interbody fusion or lateral lumbar interbody fusion with posterior screw fixation). Intraoperative, radiographic, and clinical outcomes, as well as complications, were compared between groups with ANOVA and χ2 tests. RESULTS: One-hundred and thirty-eight patients were included for study (PSF, n = 37; PSF-IB, n = 44; AP, n = 57). Intraoperatively, estimated blood loss was similar between groups (p = 0.171). However, the AP group had longer operative times (547.5 min) compared to PSF (385.1) and PSF-IB (370.7) (p < 0.001). Additionally, fusion length was shorter in PSF-IB (11.4) compared to AP (13.6) and PSF (12.9) (p = 0.004). There were no differences between the groups in terms of change in alignment from preoperative to 2 years postoperative. There were no differences in clinical outcomes. While postoperative complications were largely similar between groups, operative complications were higher in the AP group (31.6%) compared to the PSF (5.4%) and PSF-IB (9.1) groups (p < 0.001). CONCLUSION: While there were differences in intraoperative outcomes (operative time and fusion length), there were no differences in postoperative clinical or radiographic outcomes. AP fusion was associated with a higher rate of operative complications.

An electrophysiological correlate of sleep in a shark.

Sleep is a prominent physiological state observed across the animal kingdom. Yet, for some animals, our ability to identify sleep can be masked by behaviors otherwise associated with being awake, such as for some sharks that must swim continuously to push oxygenated seawater over their gills to breathe. We know that sleep in buccal pumping sharks with clear rest/activity cycles, such as draughtsboard sharks (Cephaloscyllium isabellum, Bonnaterre, 1788), manifests as a behavioral shutdown, postural relaxation, reduced responsiveness, and a lowered metabolic rate. However, these features of sleep do not lend themselves well to animals that swim nonstop. In addition to video and accelerometry recordings, we tried to explore the electrophysiological correlates of sleep in draughtsboard sharks using electroencephalography (EEG), electromyography, and electrooculography, while monitoring brain temperature. The seven channels of EEG activity had a surprising level of (apparent) instability when animals were swimming, but also when sleeping. The amount of stable EEG signals was too low for replication within- and across individuals. Eye movements were not measurable, owing to instability of the reference electrode. Based on an established behavioral characterization of sleep in draughtsboard sharks, we offer the original finding that muscle tone was strongest during active wakefulness, lower in quietly awake sharks, and lowest in sleeping sharks. We also offer several critical suggestions on how to improve techniques for characterizing sleep electrophysiology in future studies on elasmobranchs, particularly for those that swim continuously. Ultimately, these approaches will provide important insights into the evolutionary confluence of behaviors typically associated with wakefulness and sleep.

Evaluating the epizootic and zoonotic threat of an H7N9 low-pathogenicity avian influenza virus (LPAIV) variant associated with enhanced pathogenicity in turkeys.

Between 2013 and 2017, the A/Anhui/1/13-lineage (H7N9) low-pathogenicity avian influenza virus (LPAIV) was epizootic in chickens in China, causing mild disease, with 616 fatal human cases. Despite poultry vaccination, H7N9 has not been eradicated. Previously, we demonstrated increased pathogenesis in turkeys infected with H7N9, correlating with the emergence of the L217Q (L226Q H3 numbering) polymorphism in the haemagglutinin (HA) protein. A Q217-containing virus also arose and is now dominant in China following vaccination. We compared infection and transmission of this Q217-containing 'turkey-adapted' (ty-ad) isolate alongside the H7N9 (L217) wild-type (wt) virus in different poultry species and investigated the zoonotic potential in the ferret model. Both wt and ty-ad viruses demonstrated similar shedding and transmission in turkeys and chickens. However, the ty-ad virus was significantly more pathogenic than the wt virus in turkeys but not in chickens, causing 100 and 33% mortality in turkeys respectively. Expanded tissue tropism was seen for the ty-ad virus in turkeys but not in chickens, yet the viral cell receptor distribution was broadly similar in the visceral organs of both species. The ty-ad virus required exogenous trypsin for in vitro replication yet had increased replication in primary avian cells. Replication was comparable in mammalian cells, and the ty-ad virus replicated successfully in ferrets. The L217Q polymorphism also affected antigenicity. Therefore, H7N9 infection in turkeys can generate novel variants with increased risk through altered pathogenicity and potential HA antigenic escape. These findings emphasize the requirement for enhanced surveillance and understanding of A/Anhui/1/13-lineage viruses and their risk to different species.

CD163+ Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma.

BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.

Riluzole for Degenerative Cervical Myelopathy: A Secondary Analysis of the CSM-PROTECT Trial.

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention: Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures: The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results: Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance: In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

Innate protection against intrarectal SIV acquisition by a live SHIV vaccine.

Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection against SIV/HIV (SHIV) acquisition. Here, we evaluated the efficacy of an SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded, as there was no cross-reactivity between SIV and SHIV envelope antibodies. After 8 low-dose intrarectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated efficacy, compared with 6 naive controls, suggesting protection was achieved in the absence of anti-envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for preventing viral acquisition, as none of the CD8-depleted macaques were infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity, identified mechanisms, and may provide opportunities for novel HIV vaccines or therapeutic strategy development.

Neighborhood Deprivation is Associated With Hospital Length of Stay, Discharge Disposition, and Readmission Rates for Patients Who Survive Hospitalization With Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is a leading cause of disability in the United States. Limited research exists on the influence of area-level socioeconomic status and outcomes after TBI. This study investigated the correlation between the Area Deprivation Index (ADI) and (1) 90-day hospital readmission rates, (2) facility discharge, and (3) prolonged (≥5 days) hospital length of stay (LOS). METHODS: Single-center retrospective review of adult (18 years or older) patients who were admitted for TBI during 2018 was performed. Patients were excluded if they were admitted for management of a chronic or subacute hematoma. We extracted relevant clinical and demographic data including sex, comorbidities, age, body mass index, smoking status, TBI mechanism, and national ADI. We categorized national ADI rankings into quartiles for analysis. Univariate, multivariate, and area under the receiver operating characteristic curve (AUROC) analyses were performed to assess the relationship between ADI and 90-day readmission, hospital LOS, and discharge disposition. RESULTS: A total of 523 patients were included in final analysis. Patients from neighborhoods in the fourth ADI quartile were more likely to be Black (P = .007), have a body mass index ≥30 kg/m2 (P = .03), have a Charlson Comorbidity Index ≥5 (P = .004), and have sustained a penetrating TBI (P = .01). After controlling for confounders in multivariate analyses, being from a neighborhood in the fourth ADI quartile was independently predictive of 90-day hospital readmission (odds ratio [OR]: 1.35 [1.12-1.91], P = .011) (model AUROC: 0.82), discharge to a facility (OR: 1.46 [1.09-1.78], P = .03) (model AUROC: 0.79), and prolonged hospital LOS (OR: 1.95 [1.29-2.43], P = .015) (model AUROC: 0.85). CONCLUSION: After adjusting for confounders, including comorbidities, TBI mechanism/severity, and age, higher ADI was independently predictive of longer hospital LOS, increased risk of 90-day readmission, and nonhome discharge. These results may help establish targeted interventions to identify at-risk patients after TBI.

Opioid Use Prior to Adult Spine Deformity Correction Surgery is Associated With Worse Pre- and Postoperative Back Pain and Prolonged Opioid Demands.

STUDY DESIGN: Prospective multicenter database post-hoc analysis. OBJECTIVES: Opioids are frequently prescribed for painful spinal conditions to provide pain relief and to allow for functional improvement, both before and after spine surgery. Amidst a current opioid epidemic, it is important for providers to understand the impact of opioid use and its relationship with patient-reported outcomes. The purpose of this study was to evaluate pre-/postoperative opioid consumption surrounding ASD and assess patient-reported pain outcomes in older patients undergoing surgery for spinal deformity. METHODS: Patients ≥60 years of age from 12 international centers undergoing spinal fusion of at least 5 levels and a minimum 2-year follow-up were included. Patient-reported outcome scores were collected using the Numeric Rating Scale for back and leg pain (NRS-B; NRS-L) at baseline and at 2 years following surgery. Opioid use, defined based on a specific question on case report forms and question 11 from the SRS-22r questionnaire, was assessed at baseline and at 2-year follow-up. RESULT: Of the 219 patients who met inclusion criteria, 179 (81.7%) had 2-year data on opioid use. The percentages of patients reporting opioid use at baseline (n = 75, 34.2%) and 2 years after surgery (n = 55, 30.7%) were similar (P = .23). However, at last follow-up 39% of baseline opioid users (Opi) were no longer taking opioids, while 14% of initial non-users (No-Opi) reported opioid use. Regional pre- and postoperative opioid use was 5.8% and 7.7% in the Asian population, 58.3% and 53.1% in the European, and 50.5% and 40.2% in North American patients, respectively. Baseline opioid users reported more preoperative back pain than the No-Opi group (7.0 vs 5.7, P = .001), while NRS-Leg pain scores were comparable (4.8 vs 4, P = .159). Similarly, at last follow-up, patients in the Opi group had greater NRS-B scores than Non-Opi patients (3.2 vs 2.3, P = .012), but no differences in NRS-Leg pain scores (2.2 vs 2.4, P = .632) were observed. CONCLUSIONS: In this study, almost one-third of surgical ASD patients were consuming opioids both pre- and postoperatively world-wide. There were marked international variations, with patients from Asia having a much lower usage rate, suggesting a cultural influence. Despite both opioid users and nonusers benefitting from surgery, preoperative opioid use was strongly associated with significantly more back pain at baseline that persisted at 2-year follow up, as well as persistent postoperative opioid needs.

Infant mortality and social causality: Lessons from the history of Britain's public health movement, c. 1834-1914.

What are the historical conditions under which a sociologically informed understanding of health inequality can emerge in the public sphere? We seek to address this question through the lens of a strategically chosen historical puzzle-the stubborn persistence of and salient variation in high infant mortality rates across British industrial towns at the dawn of the previous century-as analysed by Arthur Newsholme, the Medical Officer of the Local Government Board. In doing so, we retrace the historical processes through which the evolving public health movement gradually helped crystallise a scientific understanding of the social causes of excess mortality. We map the dominant ideology of the public sphere at the time, chart the shifting roles of the state, and retrace the historical origins and emergence of 'public health' as a distinctive category of state policy and public discourse. We situate the public health movement in this historical configuration and identify the cracks in the existing ideological and administrative edifice through which this movement was able to articulate a novel approach to population health-one that spotlights the political economy of social inequality. We relate this historical sequence to the rise of industrial capitalism, the social fractures that it spawned, and the organised counter-movements that it necessitated.

How Do Quantitative Tissue Imaging Outcomes in Acute Ischemic Stroke Relate to Clinical Outcomes?

BACKGROUND AND PURPOSE: Infarct volume and other imaging markers are increasingly used as surrogate measures for clinical outcome in acute ischemic stroke research, but how improvements in these imaging surrogates translate into better clinical outcomes is currently unclear. We investigated how changes in infarct volume at 24 hours alter the probability of achieving good clinical outcome (modified Rankin Scale [mRS] 0-2). METHODS: Data are from endovascular thrombectomy patients from the randomized controlled ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial. Infarct volume at 24 hours was manually segmented on non-contrast computed tomography or diffusion-weighted magnetic resonance imaging. Probabilities of achieving good outcome based on infarct volume were obtained from a multivariable logistic regression model. The probability of good outcome was plotted against infarct volume using linear spline regression. RESULTS: A total of 1,099 patients were included in the analysis (median final infarct volume 24.9 mL [interquartile range: 6.6-92.2]). The relationship between total infarct volume and good outcome probability was nearly linear for infarct volumes between 0 mL and 250 mL. In this range, a 10% increase in the probability of achieving mRS 0-2 required a decrease in infarct volume of approximately 34.0 mL (95% confidence interval: -32.5 to -35.6). At infarct volumes above 250 mL, the probability of achieving mRS 0-2 probability was near zero. The relationships of tissue-specific infarct volumes and parenchymal hemorrhage volume generally showed similar patterns, although variability was high. CONCLUSION: There seems to be a near-linear association between total infarct volume and probability of achieving good outcome for infarcts up to 250 mL, whereas patients with infarct volumes greater than 250 mL are highly unlikely to have a favorable outcome.

Severe (>100 Degrees) Thoracic Adolescent Idiopathic Scoliosis - A Comparison of Surgical Approaches.

STUDY DESIGN: Retrospective. OBJECTIVE: Severe curves >100° in adolescent idiopathic scoliosis (AIS) are rare and require careful operative planning. The aim of this study was to assess baseline, perioperative, and 2-year differences between anterior release with posterior instrumentation (AP), posterior instrumentation with posterior column osteotomies (P), and posterior instrumentation with 3-column vertebral osteotomies (VCR). METHODS: Two scoliosis datasets were queried for primary cases of severe thoracic AIS (≥100°) with 2-year follow-up. Pre- and 2-year postoperative radiographic measures (2D and estimated 3D kyphosis), clinical measurements, and SRS-22 outcomes were compared between three approaches. RESULTS: Sixty-one patients were included: 16 AP (26%), 38 P (62%), 7 VCR (11%). Average age was 14.4 ± 2.0 years; 75.4% were female. Preoperative thoracic curve magnitude (AP: 112°, P: 115°, VCR: 126°, P = 0.09) and T5-T12 kyphosis (AP: 38°, P: 59°, VCR: 70°, P = 0.057) were similar between groups. Estimated 3D kyphosis was less in AP vs P (-12° vs 4°, P = 0.016). Main thoracic curves corrected to 36° in AP vs 49° and 48° for P and VCR, respectively (P = 0.02). Change in estimated 3D kyphosis was greater in AP vs P and VCR (34° vs 13°, P = 0.009; 34° vs 7°, P = 0.046). One incomplete spinal cord injury had residual deficits (P; 1/61, 1.6%). All SRS-22 domains improved postoperatively. CONCLUSION: All approaches obtained satisfactory coronal and sagittal correction, but AP had smaller residual coronal deformity and greater kyphosis restoration than the other approaches. This information may help inform the decision of whether to include an anterior release for large thoracic AIS curves.

The Dynamic Model of Health Assets: a model development.

AIM: Epidemiological research on resistance and resilience can build on models of health developed in health promotion. Nevertheless, these models need to be adjusted to approaches currently employed in epidemiology; namely, included concepts should be easy to operationalize, and links between them should be simple enough to enable statistical modeling. In addition, these models should include both individual and environmental assets. The objective of this study is to consolidate the current knowledge on health assets, adjust them to epidemiological research needs, and propose a new model of health assets for epidemiological studies on health. DESIGN: The conceptual paper was conducted according to the guidelines for the model development. METHODS: The development of the new model was made from the perspective of salutogenesis - the branch of health promotion studying the origins of health. The analysis of literature on health promotion, public health, and positive psychology was conducted to find the links connecting individual and environmental assets. RESULTS: The newly developed Dynamic Model of Health Assets circularly links individual characteristics, actions, environments, and support. Each preceding component of the model contributes to the following one; each component also independently contributes to resistance and resilience. The new model may guide large-scale epidemiological research on resistance and resilience. The model's components are easy to operationalize; the model allows for constructing multilevel models and accounting for the dynamic nature of the relationships between components. It is also generic enough to be adjusted to studying contributors to resistance and resilience to different specific diseases. CONCLUSION: The new model can guide epidemiological studies on resistance and resilience.

The CATFISH study: An evaluation of a water fluoridation program in Cumbria, UK.

OBJECTIVES: The objective was to assess the effectiveness of a Water Fluoridation program on a contemporary population of children. METHODS: The study used a longitudinal prospective cohort design. In Cumbria, England, two groups of children were recruited and observed over a period of 5-6 years. The Birth Cohort consisted of families recruited from two hospitals in Cumbria where children were conceived after water fluoridation was reintroduced. The systemic and topical effects of community water fluoridation were evaluated in the Birth Cohort. The Older Cohort were approximately 5 years old and recruited from primary schools in Cumbria, shortly after water fluoridation was reintroduced. The predominantly topical effects of fluoridated water were evaluated in the Older Cohort. The primary outcome was the proportion of children with clinical evidence of caries experience in their primary (Birth Cohort) or permanent teeth (Older Cohort). Unadjusted and adjusted regression models were used for analysis. RESULTS: The final clinical examinations for the Birth Cohort involved 1444 participants (mean age 4.8 years), where 17.4% of children in the intervention group were found to have caries experience, compared to 21.4% in the control group. A beneficial effect of water fluoridation was observed adjusting for deprivation (a socioeconomic measure), sex, and age, (adjusted odds ratio 0.74 95% CI 0.55 to 0.98). The final Older Cohort clinical examinations involved 1192 participants (mean age 10.8 years) where 19.1% of children in the intervention group were found to have caries experience compared to 21.9% in the control group (adjusted odds ratio 0.80, 95% CI 0.58 to 1.09). For both the Birth Cohort and Older Cohort there was evidence of a beneficial effect on dmft/DMFT count (IRR 0.61, 95% CI 0.44, 0.86) and (IRR 0.69, 95% CI 0.52, 0.93) respectively. No conclusive proof was found to indicate that the effectiveness of water fluoridation differed across area deprivation quintiles. CONCLUSIONS: In the contemporary context of lower caries levels and widespread use of fluoride toothpaste, the impact of water fluoridation on the prevalence of caries was smaller than previous studies have reported. It is important to consider the clinical importance of the absolute reduction in caries prevalence against the use of other dental caries preventive measures.

The 2023 WSES guidelines on the management of trauma in elderly and frail patients.

BACKGROUND: The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. METHODS: Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. RESULTS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patient's directives, family feelings and representatives' desires, and all decisions should be shared. CONCLUSIONS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

Impact of preoperative mental health diagnosis on postoperative opioid use patterns in spine fusion surgery: A systematic literature review.

Opioids are frequently prescribed for patients undergoing procedures such as spinal fusion surgery for the management of chronic back pain. However, the association between a preoperative mental health illness, such as depression or anxiety, and opioid use patterns after spinal fusion surgery remain unclear. Therefore, we performed a systematic literature review in accordance with PRISMA guidelines to identify articles from the PubMed Database that analyzed the relationship between preoperative mental health illness and postoperative opioid usage after spinal fusion surgery on June 1, 2023. The Methodological Index for Nonrandomized Studies (MINORS) was utilized to evaluate the quality of included articles. Seven studies with 139,580 patients and a mean MINORS score of 18 ± 0.5 were included in qualitative synthesis. The most common spine surgery performed was lumbar fusion (59 %) and the mean age across studies ranged from 50 to 62 years. The range of postoperative opioid usage patterns analyzed ranged from 1 to 24 months. The majority of studies (6/7; 86 %) reported that a preoperative diagnosis of mental health illness was associated with increased opioid dependence after spinal fusion surgery. Preoperative use of opioids for protracted periods was shown to be associated with postoperative chronic opioid dependence. Consensus findings suggest that having a preoperative diagnosis of a mental health illness such as depression or anxiety is associated with increased postoperative opioid use after spinal fusion surgery. Patient comorbidities, including diagnoses of mental health illness, must be considered by the spine surgeon in order to reduce rates of postoperative opioid dependence.

Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

BACKGROUND AND OBJECTIVES: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. METHODS: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. RESULTS: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. DISCUSSION: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Ion Dyshomeostasis in the Early Hyperacute Phase after a Temporary Large-Vessel Occlusion Stroke.

Element dysregulation is a pathophysiologic hallmark of ischemic stroke. Prior characterization of post-stroke element dysregulation in the photothrombotic model demonstrated significant element changes for ions that are essential for the function of the neurovascular unit. To characterize the dynamic changes during the early hyperacute phase (<6 h), we employed a temporary large-vessel occlusion stroke model. The middle cerebral artery was temporarily occluded for 30 min in male C57BL/6 mice, and coronal brain sections were prepared for histology and X-ray fluorescence microscopy from 5 to 120 min post-reperfusion. Ion dysregulation was already apparent by 5 min post-reperfusion, evidenced by reduced total potassium in the lesion. Later time points showed further dysregulation of phosphorus, calcium, copper, and zinc. By 60 min post-reperfusion, the central portion of the lesion showed pronounced element dysregulation and could be differentiated from a surrounding region of moderate dysregulation. Despite reperfusion, the lesion continued to expand dynamically with increasing severity of element dysregulation throughout the time course. Given that the earliest time point investigated already demonstrated signs of ion disruption, we anticipate such changes may be detectable even earlier. The profound ion dysregulation at the tissue level after reperfusion may contribute to hindering treatments aimed at functional recovery of the neurovascular unit.

A method for the quantitative analysis of polar anionic pesticides in milk/infant formula, cereals and fruit and vegetables using ion chromatography coupled to tandem mass spectrometry.

Polar pesticides such as anionic or ionisable compounds have always provided a challenge for analytical chemists. Methods of analysis have been developed using a range of techniques including normal phase chromatography, ion-pairing, derivatisation and HILIC or multi-mode chromatography. These work well with some of these compounds but, except for HILIC, all of them have their limitations and none of them cover the range required by legislation. Some of these compounds, glyphosate, chlorate and phosphonic acid, are found regularly in a range of food matrices, and therefore reliable methods of analysis are essential. This study describes an ion chromatography method with tandem mass spectrometry detection which not only covers the full range of compounds required by legislation but also can be expanded to include other anionic or ionisable pesticides and metabolites. These include glyphosate and its metabolites, glufosinate and its metabolites, ethephon and its metabolites as well as fosetyl aluminium, chlorate and perchlorate. The method is fully validated according to the performance criteria from the SANTE guidelines for the analysis of pesticides in food and feed over a wide range of matrices, including milk, infant formula, cereals and fruits and vegetables. Over 300 food samples have analysed as part of our routine monitoring program.