An Appraisal of the Quality of Development and Reporting of Predictive Models in Neurosurgery: A Systematic Review.

BACKGROUND AND OBJECTIVES: Significant evidence has indicated that the reporting quality of novel predictive models is poor because of confounding by small data sets, inappropriate statistical analyses, and a lack of validation and reproducibility. The Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) statement was developed to increase the generalizability of predictive models. This study evaluated the quality of predictive models reported in neurosurgical literature through their compliance with the TRIPOD guidelines. METHODS: Articles reporting prediction models published in the top 5 neurosurgery journals by SCImago Journal Rank-2 (Neurosurgery, Journal of Neurosurgery, Journal of Neurosurgery: Spine, Journal of NeuroInterventional Surgery, and Journal of Neurology, Neurosurgery, and Psychiatry) between January 1st, 2018, and January 1st, 2023, were identified through a PubMed search strategy that combined terms related to machine learning and prediction modeling. These original research articles were analyzed against the TRIPOD criteria. RESULTS: A total of 110 articles were assessed with the TRIPOD checklist. The median compliance was 57.4% (IQR: 50.0%-66.7%). Models using machine learning-based models exhibited lower compliance on average compared with conventional learning-based models (57.1%, 50.0%-66.7% vs 68.1%, 50.2%-68.1%, P = .472). Among the TRIPOD criteria, the lowest compliance was observed in blinding the assessment of predictors and outcomes (n = 7, 12.7% and n = 10, 16.9%, respectively), including an informative title (n = 17, 15.6%) and reporting model performance measures such as confidence intervals (n = 27, 24.8%). Few studies provided sufficient information to allow for the external validation of results (n = 26, 25.7%). CONCLUSION: Published predictive models in neurosurgery commonly fall short of meeting the established guidelines laid out by TRIPOD for optimal development, validation, and reporting. This lack of compliance may represent the minor extent to which these models have been subjected to external validation or adopted into routine clinical practice in neurosurgery.

Systematic Analysis of Biological Processes Reveals Gene Co-expression Modules Driving Pathway Dysregulation in Alzheimer's Disease.

Alzheimer's disease (AD) manifests as a complex systems pathology with intricate interplay among various genes and biological processes. Traditional differential gene expression (DEG) analysis, while commonly employed to characterize AD-driven perturbations, does not sufficiently capture the full spectrum of underlying biological processes. Utilizing single-nucleus RNA-sequencing data from postmortem brain samples across key regions-middle temporal gyrus, superior frontal gyrus, and entorhinal cortex-we provide a comprehensive systematic analysis of disrupted processes in AD. We go beyond the DEG-centric analysis by integrating pathway activity analysis with weighted gene co-expression patterns to comprehensively map gene interconnectivity, identifying region- and cell-type-specific drivers of biological processes associated with AD. Our analysis reveals profound modular heterogeneity in neurons and glia as well as extensive AD-related functional disruptions. Co-expression networks highlighted the extended involvement of astrocytes and microglia in biological processes beyond neuroinflammation, such as calcium homeostasis, glutamate regulation, lipid metabolism, vesicle-mediated transport, and TOR signaling. We find limited representation of DEGs within dysregulated pathways across neurons and glial cells, suggesting that differential gene expression alone may not adequately represent the disease complexity. Further dissection of inferred gene modules revealed distinct dynamics of hub DEGs in neurons versus glia, suggesting that DEGs exert more impact on neurons compared to glial cells in driving modular dysregulations underlying perturbed biological processes. Interestingly, we observe an overall downregulation of astrocyte and microglia modules across all brain regions in AD, indicating a prevailing trend of functional repression in glial cells across these regions. Notable genes from the CALM and HSP90 families emerged as hub genes across neuronal modules in all brain regions, suggesting conserved roles as drivers of synaptic dysfunction in AD. Our findings demonstrate the importance of an integrated, systems-oriented approach combining pathway and network analysis to comprehensively understand the cell-type-specific roles of genes in AD-related biological processes.

Investigating the relationship between heat load and shade seeking behaviour in dairy buffaloes.

The study presented in this Research Communication aimed to investigate the relationship between physiological responses, body surface temperature and shade-seeking behaviour in Nili Ravi dairy buffaloes during summer months. We enrolled 60 buffaloes, and each animal was observed for three consecutive days starting before sunrise until they moved towards the shade structures. A repeated measures ANOVA was employed to assess the changes in physiological parameters and body surface temperature between the early morning and the occurrence of shade-seeking behaviour. The average temperature humidity index and heat load index during the behavioural monitoring period (0400 to 1200 h) were 81.3 ± 6.5 and 92.9 ± 17, respectively (mean ± sd). There was no significant difference in core body temperature between sunrise and the time of shade-seeking event. However, the buffaloes had a slightly higher respiration rate at the time of shade-seeking (19.2 vs. 22.4 breaths/min). In addition, body surface temperature, measured at the flank region, shoulder, base of the ear and forehead was significantly higher at the occurrence of shade-seeking behaviour compared to the early morning. On average, the buffaloes sought shade when the surface temperature was 2°C higher than the temperature recorded before sunrise. Overall, the current findings suggest that body surface temperature, rather than core body temperature was strongly associated with shade-seeking behaviour in dairy buffaloes. These findings could be useful in developing strategies to mitigate the effects of heat stress in dairy buffalo herds and thereby improve animal welfare.

Systematic Analysis of Biological Processes Reveals Gene Co-expression Modules Driving Pathway Dysregulation in Alzheimer's Disease.

Alzheimer's disease (AD) manifests as a complex systems pathology with intricate interplay among various genes and biological processes. Traditional differential gene expression (DEG) analysis, while commonly employed to characterize AD-driven perturbations, does not sufficiently capture the full spectrum of underlying biological processes. Utilizing single-nucleus RNA-sequencing data from postmortem brain samples across key regions-middle temporal gyrus, superior frontal gyrus, and entorhinal cortex-we provide a comprehensive systematic analysis of disrupted processes in AD. We go beyond the DEG-centric analysis by integrating pathway activity analysis with weighted gene co-expression patterns to comprehensively map gene interconnectivity, identifying region- and cell-type-specific drivers of biological processes associated with AD. Our analysis reveals profound modular heterogeneity in neurons and glia as well as extensive AD-related functional disruptions. Co-expression networks highlighted the extended involvement of astrocytes and microglia in biological processes beyond neuroinflammation, such as calcium homeostasis, glutamate regulation, lipid metabolism, vesicle-mediated transport, and TOR signaling. We find limited representation of DEGs within dysregulated pathways across neurons and glial cells, indicating that differential gene expression alone may not adequately represent the disease complexity. Further dissection of inferred gene modules revealed distinct dynamics of hub DEGs in neurons versus glia, highlighting the differential impact of DEGs on neurons compared to glial cells in driving modular dysregulations underlying perturbed biological processes. Interestingly, we note an overall downregulation of both astrocyte and microglia modules in AD across all brain regions, suggesting a prevailing trend of functional repression in glial cells across these regions. Notable genes, including those of the CALM and HSP90 family genes emerged as hub genes across neuronal modules in all brain regions, indicating conserved roles as drivers of synaptic dysfunction in AD. Our findings demonstrate the importance of an integrated, systems-oriented approach combining pathway and network analysis for a comprehensive understanding of the cell-type-specific roles of genes in AD-related biological processes.

Development and Validation of a Questionnaire to Measure a Medical Student's Interest in the Subject of Community Medicine.

Background: Lack of interest has been cited by many studies as the predominant cause for students undervaluing the subject of Community Medicine. However, there are few valid and reliable tools that could measure this interest. To develop and validate a questionnaire to measure a medical student's interest in the subject of Community Medicine. Material and Methods: Cross-sectional study conducted at MTMC Jamshedpur. The Community Medicine Interest Questionnaire (CMIQ) was developed in two phases: item generation and item reduction. Items were generated through a review of the literature, focused group discussions, and in-depth interviews. In the item reduction phase, the content and construct validity of the questionnaire were ascertained. Content validity was carried out by a group of experts based on three parameters: the interrater agreement on the representativeness of the item, the interrater agreement on the clarity of the items, and the content validity index. The construct validity was ascertained through pilot testing of 480 responses from undergraduate medical students. Exploratory factor analysis through principal axis factoring and Promax rotation. Results: Twenty-five items were generated. Three of these items were removed following expert validation. Furthermore, three items were removed after pilot testing. The resulting CMIQ consisted of 19 items distributed over three dimensions: feeling, value, and predisposition to reengage toward the subject. The internal consistency of each of the subscales was ascertained. Conclusions: CMIQ is a valid and reliable tool that can be used to measure such interest for providing educational interventions.

Association of Malnutrition with Surgical and Hospital Outcomes after Spine Surgery for Spinal Metastases: A National Surgical Quality Improvement Program Study of 1613 Patients.

Background: Malnutrition is a common condition that may exacerbate many medical and surgical pathologies. However, few have studied the impact of malnutrition on surgical outcomes for patients undergoing surgery for metastatic disease of the spine. This study aims to evaluate the impact of malnutrition on perioperative complications and healthcare resource utilization following surgical treatment of spinal metastases. Methods: We conducted a retrospective cohort study using the 2011-2019 American College of Surgeons National Surgical Quality Improvement Program database. Adult patients with spinal metastases who underwent laminectomy, corpectomy, or posterior fusion for extradural spinal metastases were identified using the CPT, ICD-9-CM, and ICD-10-CM codes. The study population was divided into two cohorts: Nourished (preoperative serum albumin values ≥ 3.5 g/dL) and Malnourished (preoperative serum albumin values < 3.5 g/dL). We assessed patient demographics, comorbidities, intraoperative variables, postoperative adverse events (AEs), hospital LOS, discharge disposition, readmission, and reoperation. Multivariate logistic regression analyses were performed to identify the factors associated with a prolonged length of stay (LOS), AEs, non-routine discharge (NRD), and unplanned readmission. Results: Of the 1613 patients identified, 26.0% were Malnourished. Compared to Nourished patients, Malnourished patients were significantly more likely to be African American and have a lower BMI, but the age and sex were similar between the cohorts. The baseline comorbidity burden was significantly higher in the Malnourished cohort compared to the Nourished cohort. Compared to Nourished patients, Malnourished patients experienced significantly higher rates of one or more AEs (Nourished: 19.8% vs. Malnourished: 27.6%, p = 0.004) and serious AEs (Nourished: 15.2% vs. Malnourished: 22.6%, p < 0.001). Upon multivariate regression analysis, malnutrition was found to be an independent and associated with an extended LOS [aRR: 3.49, CI (1.97, 5.02), p < 0.001], NRD [saturated aOR: 1.76, CI (1.34, 2.32), p < 0.001], and unplanned readmission [saturated aOR: 1.42, CI (1.04, 1.95), p = 0.028]. Conclusions: Our study suggests that malnutrition increases the risk of postoperative complication, prolonged hospitalizations, non-routine discharges, and unplanned hospital readmissions. Further studies are necessary to identify the protocols that pre- and postoperatively optimize malnourished patients undergoing spinal surgery for metastatic spinal disease.

The Impact of Preoperative Spinal Injection Timing on Postoperative Complications of Lumbar Decompression Surgery.

BACKGROUND AND OBJECTIVES: Epidural steroid injections (ESIs) are commonly used for lower back pain management. The effect of these injections on lumbar decompression surgery outcomes is hitherto underexplored. The study objective was to determine the impact of ESIs on postoperative rates of medical and surgical complications and to define the appropriate interval before lumbar decompression surgery. METHODS: This retrospective all-payer database analysis identified 587 651 adult patients undergoing one- to three-level laminectomies from January 2010 to October 2021. A 2:1 propensity score match accounting for comorbidities, levels of surgery, and demographics was performed to create two cohorts: (1) 43 674 patients who had received an ESI in the 90 days before laminectomy and (2) 87 348 patients who had not received an ESI. The primary outcome was the rates of medical and surgical complications between groups at 30 days postoperatively. Patients were divided into five cohorts based on injection time before surgery: 1 to 30 days, 31 to 45 days, 46 to 60 days, 61 to 75 days, and 76 to 90 days. Logistic regression was performed between groups to identify temporal associations of complication rates. Confidence intervals of 95% are provided when appropriate. P values < .01 were considered significant. RESULTS: Rates of medical complications within 30 days of surgery were significantly higher in those with ESI compared with control (4.83% vs 3.9%, P < .001). Cerebrospinal fluid (CSF) leak rates were increased in the ESI group at 0.28% vs 0.1% (P < .001), but surgical site infection rates were not significantly different between groups (1.31% vs 1.42% P = .11). ESI performed within 30 days was associated with increased odds of CSF leak (OR: 5.32, 95% CI: 3.96-7.15). CONCLUSION: Preoperative ESI increases the risk of CSF leak and medical complications after lumbar decompression. Because these complications were significantly associated with ESIs given 1 to 30 days before surgery, avoiding ESIs at least 30 days before surgery may be advisable.

Racial differences in P2Y12 inhibitor responsiveness in patients undergoing neuro-endovascular procedures: A cohort from the Middle East.

BACKGROUND: Data on P2Y12 inhibitors responsiveness from the middle east is scarce. We sought to investigate patient responsiveness to P2Y12 inhibitors within a cohort of major races that characterize the UAE population. The secondary objective was to assess risk factors for hyper and hypo-responsiveness in this population. METHODS: We conducted a cross-sectional study on adults who received either clopidogrel or ticagrelor treatments and had platelet responsiveness testing before undergoing neuro-endovascular interventions at our quaternary care hospital between March 2015 and April 2019. RESULTS: During the study period, 249 subjects met the inclusion criteria. Overall, 17.3 % were hyper-responsive and 25.7 % were hypo-responsive to P2Y12 inhibitors. When comparing between the P2Y12 inhibitors, rates of hyper-responsiveness were significantly higher to ticagrelor when compared to clopidogrel (11 versus 6 %, p = 0.02 respectively). Contrarily, hypo-responsiveness rates were significantly higher in clopidogrel treated patients compared to their ticagrelor treated counterparts (23 versus 2 %, p < .001 respectively). Patients of Middle-Eastern origin showed a significantly higher rate of hypo-responsiveness to both clopidogrel and ticagrelor when compared to other races (41.1 % and 26.7 %, P < 0.001 respectively). Asians showed the highest rates of hyper-responsiveness for both agents. Multivariate logistic regression analysis showed that proton pump inhibitors and statin combination, (OR: 6.39, 95 %CI [1.60, 25.392]), and Middle East vs. Indian subcontinent patients (OR: 4.67, 95 %CI [1.79-12.14]) were independent predictors of hypo-responsiveness to both P2Y12 inhibitors. CONCLUSION: This study demonstrated a high rate of hypo-responsiveness to P2Y12 inhibitors in a UAE cohort of patients undergoing neuro-endovascular procedures. In addition, therapeutic responsiveness to P2Y12 inhibitors varied markedly based on the racial background. Future larger studies are needed to evaluate genetic variations that may contribute to this rate of hypo-responsiveness in our population.

Assessing the efficacy of VerifyNow platelet-function testing in predicting postoperative hemorrhagic complications of neuroendovascular surgery: A systematic review and meta-analysis (part 2).

BACKGROUND: Dual antiplatelet therapy is used to reduce the risk of thromboembolic complications in neuroendovascular surgery. However, the predictive utility of preoperative platelet-sensitivity testing for decreasing bleed risk in patients undergoing endovascular neurointervention remains unclear. OBJECTIVE: We conducted a systematic review and meta-analysis to illustrate the association between platelet response and risk of hemorrhagic complications from neuroendovascular surgery, examine the efficacy of the VerifyNow platelet reactivity unit (PRU) assay in predicting hemorrhagic outcomes, and assess whether a clinically useful threshold for platelet response can be defined to standardize guidelines. METHODS: PubMed, Embase, and Scopus were searched. Articles were screened for relevance by title and abstract, followed by full text. RESULTS: Of 735 resultant articles, 17 studies of 2084 patients undergoing neuroendovascular intervention were included. Diagnoses included both intracranial and extracranial pathologies, of which 37.8% were treated with flow diversion, 22.4% with stent-assisted coil embolization, 14.3% with intracranial stenting, 12.8% with simple coil embolization, 5.8% with balloon-assisted coil embolization, 2.0% with extracranial stenting, and 4.8% with an alternate method. Precisely, 52.9% (9 out of 17) of studies determined platelet hyperresponse to be an independent predictor of postoperative hemorrhagic complications, with 11.8% (2 out of 17) of studies reporting a similar but non-statistically significant trend. 35.3% (6 out of 17) of studies found no relationship between platelet response and postoperative hemorrhagic complications. The estimated clinical threshold for PRU to prevent hemorrhagic complications varied considerably across studies (range: <46-118 PRU). Meta-analysis found platelet hyperresponse to have more than a 3-fold increased risk of hemorrhagic complications compared to normoresponders (relative risk = 3.2, p = 0.001). CONCLUSION: Although this meta-analysis shows the predictive utility of the P2Y12 assay for postoperative hemorrhagic complications in neuroendovascular surgery, the optimal therapeutic threshold for minimizing bleeding risk is still uncertain. To better understand the utility of the P2Y12 assay in the perioperative period, further prospective research is needed.

Assessing the efficacy of VerifyNow platelet-function testing in predicting postoperative thromboembolic complications of neuroendovascular surgery: A systematic review and meta-analysis (part 1).

BACKGROUND: Despite the heavily debated use of routine platelet-function testing, the VerifyNow Platelet Reactivity Unit (PRU) assay has been increasingly adopted as standard of care for assessing risk of postoperative thromboembolic complications of neuroendovascular surgery. OBJECTIVE: We conducted a systematic review and meta-analysis to examine the relationship between platelet response and risk of ischemic events from neuroendovascular surgery, assess the efficacy of point-of-care platelet-function testing in predicting thromboembolic outcomes, and assess whether a clinically useful threshold for platelet response can be defined in order to standardize guidelines. METHODS: PubMed, Embase, and Scopus were searched. Following deduplication, articles were first screened for relevance by title and abstract, followed by full text. RESULTS: Of 735 resultant articles, 22 studies consisting of 3266 patients undergoing neuroendovascular intervention were included. Diagnoses included both intracranial and extracranial pathologies, of which 45.8% were treated with flow diversion, 16.4% with stent-assisted coil embolization, 15.8% with intracranial stenting, 12.0% with simple coil embolization, 3.4% with balloon-assisted coil embolization, 3.6% with extracranial stenting, and 3.0% with an alternate method. 54.5% (12/22) of studies determined platelet hyporesponse to be an independent predictor of postoperative thromboembolic complications, with 27.3% (6/22) of studies reporting a similar, but non-statistically significant trend. 18.2% (4/22) of studies found no relationship between platelet response and postoperative thromboembolic complications. The estimated clinical threshold for PRU to prevent thromboembolic complications varied greatly across studies (Range: > 144-295 PRU). Meta-analysis found platelet hyporesponse to have a 2.23-fold increased risk of thromboembolic complications compared to normoresponders (RR = 2.23, P = 0.03). CONCLUSION: While PRU demonstrates a significant predictive value for postoperative thromboembolic complications of neuroendovascular surgery, the target therapeutic threshold for minimizing ischemic events remains unclear. Further studies, such as large multicenter cohorts of the existing data, are needed to standardize guidelines.

Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD.

Functional loss of TDP-43, an RNA binding protein genetically and pathologically linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leads to the inclusion of cryptic exons in hundreds of transcripts during disease. Cryptic exons can promote the degradation of affected transcripts, deleteriously altering cellular function through loss-of-function mechanisms. Here, we show that mRNA transcripts harboring cryptic exons generated de novo proteins in TDP-43-depleted human iPSC-derived neurons in vitro, and de novo peptides were found in cerebrospinal fluid (CSF) samples from patients with ALS or FTD. Using coordinated transcriptomic and proteomic studies of TDP-43-depleted human iPSC-derived neurons, we identified 65 peptides that mapped to 12 cryptic exons. Cryptic exons identified in TDP-43-depleted human iPSC-derived neurons were predictive of cryptic exons expressed in postmortem brain tissue from patients with TDP-43 proteinopathy. These cryptic exons produced transcript variants that generated de novo proteins. We found that the inclusion of cryptic peptide sequences in proteins altered their interactions with other proteins, thereby likely altering their function. Last, we showed that 18 de novo peptides across 13 genes were present in CSF samples from patients with ALS/FTD spectrum disorders. The demonstration of cryptic exon translation suggests new mechanisms for ALS/FTD pathophysiology downstream of TDP-43 dysfunction and may provide a potential strategy to assay TDP-43 function in patient CSF.

5-year stroke rates in nonvalvular atrial fibrillation after watchman compared to direct oral anticoagulants.

BACKGROUND: The WATCHMAN device (Boston Scientific; Marlborough, MA, USA) is noninferior to warfarin in preventing ischemic strokes while reducing bleeding risks associated with long term anticoagulation in nonvalvular atrial fibrillation (AFib). The device's performance compared to direct oral anticoagulants (DOAC) is less well known. OBJECTIVE: To compare 5-year major bleeding and ischemic stroke rates in patients with nonvalvular AFib who received a WATCHMAN device or DOAC therapy after a major bleeding event. METHODS: This retrospective, multicenter, 1:1 matched cohort study was derived from the PearlDiver Mariner database from 2010 to 2020. Patients with nonvalvular AFib on oral anticoagulation who had a major bleeding event were identified. Those who received either WATCHMAN or DOAC after resolution of the bleeding event were selected. The two groups were exactly matched 1:1 based on various comorbidities. Rates of ischemic stroke, transient ischemic attack (TIA), major bleeding, and hemorrhagic stroke were compared over 5 years. RESULTS: Each cohort consisted of 2248 patients after 1:1 matching. The mean CHADS2-VASC score was 4.81 ±â€¯1.25. At 5 years, the WATCHMAN cohort had significantly lower rates of major bleeding events [OR 0.24 (0.21, 0.27)], TIAs [OR 0.75 (0.58, 0.95)], and ischemic strokes [OR 0.72 (0.61, 0.86)]. There was no significant difference in hemorrhagic strokes [OR 1.14 (0.83, 1.58)]. CONCLUSION: Even in a high-risk population, the WATCHMAN is comparable to DOAC therapy in the primary prevention of hemorrhagic strokes and may provide benefit in the rates of bleeding events, TIAs, and ischemic strokes.

Test Retest Reproducibility of Organ Volume Measurements in ADPKD Using 3D Multimodality Deep Learning.

RATIONALE AND OBJECTIVES: Following autosomal dominant polycystic kidney disease (ADPKD) progression by measuring organ volumes requires low measurement variability. The objective of this study is to reduce organ volume measurement variability on MRI of ADPKD patients by utilizing all pulse sequences to obtain multiple measurements which allows outlier analysis to find errors and averaging to reduce variability. MATERIALS AND METHODS: In order to make measurements on multiple pulse sequences practical, a 3D multi-modality multi-class segmentation model based on nnU-net was trained/validated using T1, T2, SSFP, DWI and CT from 413 subjects. Reproducibility was assessed with test-re-test methodology on ADPKD subjects (n = 19) scanned twice within a 3-week interval correcting outliers and averaging the measurements across all sequences. Absolute percent differences in organ volumes were compared to paired students t-test. RESULTS: Dice similarlity coefficient > 97%, Jaccard Index > 0.94, mean surface distance < 1 mm and mean Hausdorff Distance < 2 cm for all three organs and all five sequences were found on internal (n = 25), external (n = 37) and test-re-test reproducibility assessment (38 scans in 19 subjects). When averaging volumes measured from five MRI sequences, the model automatically segmented kidneys with test-re-test reproducibility (percent absolute difference between exam 1 and exam 2) of 1.3% which was better than all five expert observers. It reliably stratified ADPKD into Mayo Imaging Classification (area under the curve=100%) compared to radiologist. CONCLUSION: 3D deep learning measures organ volumes on five MRI sequences leveraging the power of outlier analysis and averaging to achieve 1.3% total kidney test-re-test reproducibility.

Machine learning-based detection of sarcopenic obesity and association with adverse outcomes in patients undergoing surgical treatment for spinal metastases.

OBJECTIVE: The distributions and proportions of lean and fat tissues may help better assess the prognosis and outcomes of patients with spinal metastases. Specifically, in obese patients, sarcopenia may be easily overlooked as a poor prognostic indicator. The role of this body phenotype, sarcopenic obesity (SO), has not been adequately studied among patients undergoing surgical treatment for spinal metastases. To this end, here the authors investigated the role of SO as a potential prognostic factor in patients undergoing surgical treatment for spinal metastases. METHODS: The authors identified patients who underwent surgical treatment for spinal metastases between 2010 and 2020. A validated deep learning approach evaluated sarcopenia and adiposity on routine preoperative CT images. Based on composition analyses, patients were classified with SO or nonsarcopenic obesity. After nearest-neighbor propensity matching that accounted for confounders, the authors compared the rates and odds of postoperative complications, length of stay, 30-day readmission, and all-cause mortality at 90 days and 1 year between the SO and nonsarcopenic obesity groups. RESULTS: A total of 62 patients with obesity underwent surgical treatment for spinal metastases during the study period. Of these, 37 patients had nonsarcopenic obesity and 25 had SO. After propensity matching, 50 records were evaluated that were equally composed of patients with nonsarcopenic obesity and SO (25 patients each). Patients with SO were noted to have increased odds of nonhome discharge (OR 6.0, 95% CI 1.69-21.26), 30-day readmission (OR 3.27, 95% CI 1.01-10.62), and 90-day (OR 4.85, 95% CI 1.29-18.26) and 1-year (OR 3.78, 95% CI 1.17-12.19) mortality, as well as increased time to mortality after surgery (12.60 ± 19.84 months vs 37.16 ± 35.19 months, p = 0.002; standardized mean difference 0.86). No significant differences were noted in terms of length of stay or postoperative complications when comparing the two groups (p > 0.05). CONCLUSIONS: The SO phenotype was associated with increased odds of nonhome discharge, readmission, and postoperative mortality. This study suggests that SO may be an important prognostic factor to consider when developing care plans for patients with spinal metastases.

The Impact of Preoperative Antithrombotic Therapy on the Risks for Thrombo-ischemic Events and Bleeding among Patients Undergoing Elective Spine Surgery.

STUDY DESIGN: Retrospective matched analysis. PURPOSE: To evaluate the effect of antithrombotic drug therapy on the rates of thrombo-ischemic or bleeding events 90 days following elective spine surgery. OVERVIEW OF LITERATURE: Thrombo-ischemic and bleeding complications in patients undergoing spine surgery are major causes of morbidity. Many patients who pursue elective spine surgery are concurrently receiving antithrombotic therapy for unrelated conditions; however, at this time, the effects of preoperative antithrombotic use on postoperative bleeding and thrombosis are unclear. METHODS: Using an all-payer claims database, patients who underwent elective cervical and lumbar spine interventions between January 1, 2010, and June 30, 2018, were identified. Individuals were categorized into groups taking and not taking antithrombotics. A 1:1 analysis was constructed based on comorbidities found to be independently associated with bleeding or ischemic complications using logistic regression models. The primary outcomes were the rates of thrombo-ischemic events and bleeding complications. RESULTS: A total of 660,866 patients were eligible for inclusion. Following the matching procedure, 56,476 patient records were analyzed, with 28,238 in each group. The antithrombotic agent group had significantly greater odds of developing any 90-day thromboischemic event after surgery: deep vein thrombosis (odds ratio [OR], 3.61; 95% confidence interval [CI], 3.06-4.25), pulmonary embolism (OR, 3.93; 95% CI, 3.34-4.62), myocardial infarction (OR, 6.20; 95% CI, 5.69-6.76), and ischemic stroke (OR, 3.76; 95% CI, 3.31-4.27). In addition, the antithrombotic agent group had an increased likelihood of experiencing hematoma (OR, 1.54; 95% CI, 1.35-1.76) and need for transfusion (OR, 2.61; 95% CI, 2.29-2.96). CONCLUSIONS: Patients taking antithrombotic medications before elective surgery of the cervical and lumbar spine had increased risks of both ischemic and bleeding events. Spine surgeons should carefully consider these implications when appraising patients for surgery, given the lack of guidelines on perioperative management of antithrombotic agents.

Sputnik V vaccine perception and hesitancy in a tertiary health care centre transformed to Covid-19 vaccine centre: A case study.

BACKGROUND: Sputnik V vaccine was approved in India in April 2021 to tackle the pandemic situation. However, there was lack of information on the effects, side effects, and peoples' perception toward it. The present case study aims to evaluate the vaccine coverage, the awareness, and perception toward it and compare the adverse effects after each dose. MATERIALS AND METHODS: A unique case study was conducted in a sample of 200 participants comparing 2 groups of population who took first and second dose of Sputnik V vaccine during June to November 2021. The data were collected by a prevalidated questionnaire, follow-up telephonic interviews focused on knowledge, awareness, side effects of vaccine, and analyzed using descriptive statistics such as frequency, percentages, mean, and standard deviation. RESULTS: The vaccine coverage for first and second doses were 98.3% and 96.5%, respectively. The mean age of the participant was 29 + 9.5 years and majority 68.5% were males. Seventeen percent experienced the S/E for the vaccine with 9.5% from second dose. There were usual side effects; however, it was more after second dose of vaccination. Friends and healthcare workers were the main source of information (33.5%) and motivation (43%). Majority (73.5%) were aware of the side effects. Forty three point five percent took vaccine attributed to its protective role, availability, and peer pressure. There was no significant association between type of doses and side effects of the respective doses of vaccine. CONCLUSION: The vaccine coverage was >90%. Participants were well aware of the vaccine and side effects which were more in second dose. However, there was no significant difference between the two doses of vaccine.

Outcomes Following 2-Level Cervical Interventions with Cage-and-Plate, Zero-Profile, or Arthroplasty Constructs.

BACKGROUND: Though cage-and-plate constructs are widely used for disk height restoration in surgery for cervical disc disease, concerns over range of motion limitations and adjacent disc space violations have fueled the development of artificial disc and zero-profile constructs. This study investigated the outcomes of patients undergoing two-level cervical interventions via arthroplasty, cage-and-plate, or zero-profile constructs. METHODS: Patients undergoing two-level anterior cervical procedures between 2010 and 2020 were identified using an all-payer claims database. Logistic regression models were utilized to develop criteria for a 1:1:1-exact match procedure. The primary outcome was the need for additional surgery within 30 months, and the secondary outcomes included medical and surgical complications observed within 30 days of index intervention. P values < 0.05 were considered statistically significant. RESULTS: 133,831 patients were identified as undergoing two-level anterior cervical interventions. Seven thousand three hundred seventy-one records were analyzed through a 1:1:1 match. Patients who received zero-profile versus cage-and-plate constructs had significantly decreased odds of requiring additional surgery within 30 months (Odds Ratio [OR] 0.64; 95% Confidence Interval [CI] 0.51-0.81). However, postoperative medical complications were increased among patients who received zero-profile constructs compared to cage-and-plate (OR 1.59; 95%CI 1.07-2.37). Patients who underwent arthroplasty also had decreased odds for additional surgery versus cage-and-plate (OR 0.75; 95%CI 0.60-0.93). There was no significant difference between arthroplasty and cage-and-plate constructs in developing postoperative surgical or medical complications. CONCLUSIONS: Among patients undergoing two-level interventions, cage-and-plate constructs were associated with increased odds of additional surgery within 30 months following index procedures when compared to zero-profile constructs or arthroplasty.

Divergent patterns of healthy aging across human brain regions at single-cell resolution reveal links to neurodegenerative disease.

Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Previous studies reported that chronological age correlates with differential gene expression across different brain regions. However, prior datasets have not disambiguated whether expression associations with age are due to changes in cell numbers and/or gene expression per cell. In this study, we leveraged single nucleus RNA-sequencing (snRNAseq) to examine changes in cell proportions and transcriptomes in four different brain regions, each from 12 donors aged 20-30 years (young) or 60-85 years (old). We sampled 155,192 nuclei from two cortical regions (entorhinal cortex and middle temporal gyrus) and two subcortical regions (putamen and subventricular zone) relevant to neurodegenerative diseases or the proliferative niche. We found no changes in cellular composition of different brain regions with healthy aging. Surprisingly, we did find that each brain region has a distinct aging signature, with only minor overlap in differentially associated genes across regions. Moreover, each cell type shows distinct age-associated expression changes, including loss of protein synthesis genes in cortical inhibitory neurons, axonogenesis genes in excitatory neurons and oligodendrocyte precursor cells, enhanced gliosis markers in astrocytes and disease-associated markers in microglia, and genes critical for neuron-glia communication. Importantly, we find cell type-specific enrichments of age associations with genes nominated by Alzheimer's disease and Parkinson's disease genome-wide association studies (GWAS), such as apolipoprotein E (APOE), and leucine-rich repeat kinase 2 (LRRK2) in microglia that are independent of overall expression levels across cell types. We present this data as a new resource which highlights, first, region- and cell type-specific transcriptomic changes in healthy aging that may contribute to selective vulnerability and, second, provide context for testing GWAS-nominated disease risk genes in relevant subtypes and developing more targeted therapeutic strategies. The data is readily accessible without requirement for extensive computational support in a public website, https://brainexp-hykyffa56a-uc.a.run.app/.

Implication of nutritional status for adverse outcomes after surgery for metastatic spine tumors.

OBJECTIVE: Surgery for metastatic spinal tumors can have a substantial impact on patients' quality of life by alleviating pain, improving function, and correcting spinal instability when indicated. The decision to operate is difficult because many patients with cancer are frail. Studies have highlighted the importance of preoperative nutritional status assessments; however, little is known about which aspects of nutrition accurately inform clinical outcomes. This study investigates the interaction and prognostic importance of various nutritional and frailty measures in patients with spinal metastases. METHODS: A retrospective analysis of consecutive patients who underwent surgery for spinal metastases between 2014 and 2020 at the Massachusetts General Hospital was performed. Patients were stratified according to the New England Spinal Metastasis Score (NESMS). Frailty was assessed using the metastatic spinal tumor frailty index. Nutrition was assessed using the prognostic nutritional index (PNI), preoperative body mass index, albumin, albumin-to-globulin ratio, and platelet-to-lymphocyte ratio. Outcomes included postoperative survival and complication rates, with focus on wound-related complications. RESULTS: This study included 154 individuals (39% female; mean [SD] age 63.23 [13.14] years). NESMS 0 and NESMS 3 demonstrated the highest proportions of severely frail patients (56.2%) and nonfrail patients (16.1%), respectively. Patients with normal nutritional status (albumin-to-globulin ratio and PNI) had a better prognosis than those with poor nutritional status when stratified by NESMS. Multivariable regression adjusted for NESMS and frailty showed that a PNI > 40.4 was significantly associated with decreased odds of 90-day complications (OR 0.93, 95% CI 0.85-0.98). After accounting for age, sex, primary tumor pathology, physical function, nutritional status, and frailty, a preoperative nutrition consultation was associated with a decrease in postoperative wound-related complications (average marginal effect -5.00%; 95% CI -1.50% to -8.9%). CONCLUSIONS: The PNI was most predictive of complications and may be a key biomarker for risk stratification in the 90 days following surgery. Nutrition consultation was associated with a reduced risk of wound-related complications, attesting to the importance of this preoperative intervention. These findings suggest that nutrition plays an important role in the postsurgical course and should be considered when developing a treatment plan for spinal metastases.

Hospital Outcomes in Patients Hospitalized for COVID-19 Pneumonia: The Effect of SARS-CoV-2 Vaccination and Vitamin D Status.

SARS-CoV-2 vaccination promises to improve outcomes for patients with COVID-19 pneumonia (most notably those with advanced age and at high risk for severe disease). Here, we examine serum 25-Hydroxyvitamin D (25(OH)D) status and outcomes in both old (>70 years) and young vaccinated (n = 80) and unvaccinated (n = 91) subjects, who were hospitalized due to COVID-19 pneumonia in a single center (Connolly Hospital Dublin). Outcomes included ICU admission and mortality. Serum 25(OH)D levels were categorized as D30 (<30 nmol/L), D40 (30-49.99 nmol/L) and D50 (≥50 nmol/L). In multivariate analyses, D30 was independently associated with ICU admission (OR: 6.87 (95% CI: 1.13-41.85) (p = 0.036)) and mortality (OR: 24.81 (95% CI: 1.57-392.1) (p = 0.023)) in unvaccinated patients, even after adjustment for major confounders including age, sex, obesity and pre-existing diabetes mellitus. While mortality was consistently higher in all categories of patients over 70 years of age, the highest observed mortality rate of 50%, seen in patients over 70 years with a low vitamin D state (D30), appeared to be almost completely corrected by either vaccination, or having a higher vitamin D state, i.e., mortality was 14% for vaccinated patients over 70 years with D30 and 16% for unvaccinated patients over 70 years with a 25(OH)D level greater than 30 nmol/L. We observe that high mortality from COVID-19 pneumonia occurs in older patients, especially those who are unvaccinated or have a low vitamin D state. Recent vaccination or having a high vitamin D status are both associated with reduced mortality, although these effects do not fully mitigate the mortality risk associated with advanced age.