Association of plasma GFAP with elevated brain amyloid is dependent on severity of white matter lesions in an Asian cognitively impaired cohort.

INTRODUCTION: While elevated blood glial fibrillary acidic protein (GFAP) has been associated with brain amyloid pathology, whether this association occurs in populations with high cerebral small vessel disease (CSVD) concomitance remains unclear. METHODS: Using a Singapore-based cohort of cognitively impaired subjects, we assessed associations between plasma GFAP and neuroimaging measures of brain amyloid and CSVD, including white matter hyperintensities (WMH). We also examined the diagnostic performance of plasma GFAP in detecting brain amyloid beta positivity (Aß+). RESULTS: When stratified by WMH status, elevated brain amyloid was associated with higher plasma GFAP only in the WMH- group (ß = 0.383; P < 0.001). The diagnostic performance of plasma GFAP in identifying Aß+ was significantly higher in the WMH- group (area under the curve [AUC] = 0.896) than in the WMH+ group (AUC = 0.712, P = 0.008). DISCUSSION: The biomarker utility of plasma GFAP in detecting brain amyloid pathology is dependent on the severity of concomitant WMH. Highlight: Glial fibrillary acidic protein (GFAP)'s association with brain amyloid is unclear in populations with high cerebral small vessel disease (CSVD).Plasma GFAP was measured in a cohort with CSVD and brain amyloid.Plasma GFAP was better in detecting amyloid in patients with low CSVD versus high CSVD.Biomarker utility of GFAP in detecting brain amyloid depends on the severity of CSVD.

A Nationwide Analysis of the Impact of Socioeconomic Status on Complications and Healthcare Utilizations After Total Knee Arthroplasty Using the Area Deprivation Index: Consideration of the Disadvantaged Patient.

INTRODUCTION: Socioeconomic status (SES) has been demonstrated to be an important prognostic risk factor among patients undergoing total joint arthroplasty. We evaluated patients living near neighborhoods with higher socioeconomic risk undergoing total knee arthroplasty (TKA) and if they were associated with differences in: 1) medical complications; 2) emergency department (ED) utilizations; 3) readmissions; and 4) costs of care. METHODS: A query of a national database from 2010 to 2020 was performed for primary TKAs. The Area Deprivation Index (ADI) is a weighted index comprised of 17 census-based markers of material deprivation and poverty. Higher numbers indicate a greater disadvantage. Patients undergoing TKA in zip codes associated with high ADI (90%+) were 1:1 propensity-matched to a comparison group by age, sex, and Elixhauser Comorbidity Index (ECI). This yielded 225,038 total patients, evenly matched between cohorts. Outcomes studied included complications, ED utilizations, readmission rates, and 90-day costs. Logistic regression models computed the odds ratios (OR) of ADI on the dependent variables. P-values less than 0.003 were significant. RESULTS: High ADI led to higher rates and odds of any medical complications (11.7 versus 11.0%; OR: 1.05, P = 0.0006), respiratory failures (0.4 versus 0.3%; OR: 1.28, P = 0.001), and acute kidney injuries (1.7 versus 1.5%; OR: 1.15, P < 0.0001). Despite lower readmission rates (2.9 versus 3.5%), high ADI patients had greater 90-day ED visits (4.2 versus 4.0%; OR: 1.07, P = 0.0008). The 90-day expenditures ($15,066 versus $12,459; P < 0.0001) were higher in patients who have a high ADI. CONCLUSION: Socioeconomically disadvantaged patients have increased complications and ED utilizations. Neighborhood disadvantage may inform healthcare policy and improve post-discharge care. The SES metrics, including ADI (which captures community effects), should be used to adequately risk-adjust or risk-stratify patients so that access to care for deprived regions and patients is not lost.

Modern Internet Search Analytics: Is There a Difference in What Patients are Searching Regarding the Operative and Nonoperative Management of Scoliosis?

STUDY DESIGN: Observational Study. OBJECTIVES: This study aimed to investigate the most searched types of questions and online resources implicated in the operative and nonoperative management of scoliosis. METHODS: Six terms related to operative and nonoperative scoliosis treatment were searched on Google's People Also Ask section on October 12, 2023. The Rothwell classification was used to sort questions into fact, policy, or value categories, and associated websites were classified by type. Fischer's exact tests compared question type and websites encountered between operative and nonoperative questions. Statistical significance was set at the .05 level. RESULTS: The most common questions concerning operative and nonoperative management were fact (53.4%) and value (35.5%) questions, respectively. The most common subcategory pertaining to operative and nonoperative questions were specific activities/restrictions (21.7%) and evaluation of treatment (33.3%), respectively. Questions on indications/management (13.2% vs 31.2%, P < .001) and evaluation of treatment (10.1% vs 33.3%, P < .001) were associated with nonoperative scoliosis management. Medical practice websites were the most common website to which questions concerning operative (31.9%) and nonoperative (51.4%) management were directed to. Operative questions were more likely to be directed to academic websites (21.7% vs 10.0%, P = .037) and less likely to be directed to medical practice websites (31.9% vs 51.4%, P = .007) than nonoperative questions. CONCLUSIONS: During scoliosis consultations, spine surgeons should emphasize the postoperative recovery process and efficacy of conservative treatment modalities for the operative and nonoperative management of scoliosis, respectively. Future research should assess the impact of website encounters on patients' decision-making.

The Association of Dental Caries or Dental Implant Placement Within One Year of Primary Total Hip Arthroplasty on Medical and Implant Complications.

INTRODUCTION: Total hip arthroplasty (THA) adverse events among patients who have dental diagnoses remain unclear. We sought to determine if dental caries or dental implant placements increased: 1) 90-day medical complications; 2) 90-day readmissions; and 3) 2-year implant-related complications, including periprosthetic joint infections (PJIs) after THA. METHODS: A nationwide database for primary THAs from 2010 to 2021 was queried to compare three patient cohorts. Patients who had a history of dental implants or caries within 12 months prior to THA (n = 1,179) or 12 months after THA (n = 1,218) were case-matched to patients who did not have dental history (n = 6,090) by age and comorbidities. Outcomes included 90-day complications, 90-day readmissions, and 2-year implant-related complications. Logistic regression models computed the odds ratios (OR) of complications and readmissions. P values less than 0.006 were significant. RESULTS: Patients who had dental caries or implant placement 12 months before or after THA experienced 1.6-fold greater odds of 90-day medical complications compared to case-matched patients. Readmissions within 90 days increased for patients who had a dental history before (11.7 versus 8.3%; OR: 1.49, P < 0.0001) and after (14.2 versus 8.3%; OR: 1.84, P < 0.0001) THA compared to case-matched patients. A dental caries diagnosis or dental implant placement within 12 months following THA increased 2-year implant complications compared to case-matched patients (15.2 versus 9.3%; OR: 1.69, P < 0.0001), including PJIs (5.3 versus 2.8%; OR: 1.98, P < 0.0001), dislocations (4.4 versus 2.7%; OR: 1.63, P = 0.002), and THA revisions (3.9 versus 2.5%; OR: 1.61, P = 0.005). CONCLUSION: Dental diagnoses within 12 months of THA are associated with increased medical complications. Dental diagnoses occurring 12 months after THA are associated with greater implant-related complications, including PJIs. Delaying invasive dental procedures for 12 months after THA may be advisable.

The ABC toxin complex from Yersinia entomophaga can package three different cytotoxic components expressed from distinct genetic loci in an unfolded state: the structures of both shell and cargo.

Bacterial ABC toxin complexes (Tcs) comprise three core proteins: TcA, TcB and TcC. The TcA protein forms a pentameric assembly that attaches to the surface of target cells and penetrates the cell membrane. The TcB and TcC proteins assemble as a heterodimeric TcB-TcC subcomplex that makes a hollow shell. This TcB-TcC subcomplex self-cleaves and encapsulates within the shell a cytotoxic `cargo' encoded by the C-terminal region of the TcC protein. Here, we describe the structure of a previously uncharacterized TcC protein from Yersinia entomophaga, encoded by a gene at a distant genomic location from the genes encoding the rest of the toxin complex, in complex with the TcB protein. When encapsulated within the TcB-TcC shell, the C-terminal toxin adopts an unfolded and disordered state, with limited areas of local order stabilized by the chaperone-like inner surface of the shell. We also determined the structure of the toxin cargo alone and show that when not encapsulated within the shell, it adopts an ADP-ribosyltransferase fold most similar to the catalytic domain of the SpvB toxin from Salmonella typhimurium. Our structural analysis points to a likely mechanism whereby the toxin acts directly on actin, modifying it in a way that prevents normal polymerization.

GPT-4 as a Source of Patient Information for Anterior Cervical Discectomy and Fusion: A Comparative Analysis Against Google Web Search.

STUDY DESIGN: Comparative study. OBJECTIVES: This study aims to compare Google and GPT-4 in terms of (1) question types, (2) response readability, (3) source quality, and (4) numerical response accuracy for the top 10 most frequently asked questions (FAQs) about anterior cervical discectomy and fusion (ACDF). METHODS: "Anterior cervical discectomy and fusion" was searched on Google and GPT-4 on December 18, 2023. Top 10 FAQs were classified according to the Rothwell system. Source quality was evaluated using JAMA benchmark criteria and readability was assessed using Flesch Reading Ease and Flesch-Kincaid grade level. Differences in JAMA scores, Flesch-Kincaid grade level, Flesch Reading Ease, and word count between platforms were analyzed using Student's t-tests. Statistical significance was set at the .05 level. RESULTS: Frequently asked questions from Google were varied, while GPT-4 focused on technical details and indications/management. GPT-4 showed a higher Flesch-Kincaid grade level (12.96 vs 9.28, P = .003), lower Flesch Reading Ease score (37.07 vs 54.85, P = .005), and higher JAMA scores for source quality (3.333 vs 1.800, P = .016). Numerically, 6 out of 10 responses varied between platforms, with GPT-4 providing broader recovery timelines for ACDF. CONCLUSIONS: This study demonstrates GPT-4's ability to elevate patient education by providing high-quality, diverse information tailored to those with advanced literacy levels. As AI technology evolves, refining these tools for accuracy and user-friendliness remains crucial, catering to patients' varying literacy levels and information needs in spine surgery.

Conceptualizing Sexual Wellbeing: A Qualitative Investigation to Inform Development of a Measure (Natsal-SW).

Despite increasing scientific and policy interest in sexual wellbeing, it remains poorly conceptualized. Many studies purporting to measure it instead measure related but distinct concepts, such as sexual satisfaction. This lack of conceptual clarity impedes understanding, measuring, and improving sexual wellbeing. We present qualitative research from multi-stage, mixed-methods work to develop a new measure of sexual wellbeing (Natsal-SW) for the fourth British National Survey of Sexual Attitudes & Lifestyles. Literature review and discussion generated a conceptual framework with seven proposed domains: respect, self-esteem, comfort, self-determination, safety and security, forgiveness, and resilience. Semi-structured interviews with 40 adults aged 18-64 then explored whether and how these domains aligned with participants' own understandings, experiences, and language of sexual wellbeing. Data were analyzed thematically. Participants conceptualized sexual wellbeing as distinct from sexual satisfaction and sexual health and as multidimensional, dynamic, and socially and structurally influenced. All seven proposed domains resonated with accounts of sexual wellbeing as a general construct. The personal salience of different domains and their dimensions varied between individuals (especially by gender and sexual orientation) and fluctuated individually over time. This study clarifies dimensions of domains that participants considered important, providing an empirical basis to inform development of a new measure of sexual wellbeing.

How-To Create an Orthopaedic Systematic Review: A Step-by-Step Guide Part I: Study Design.

Systematic reviews are conducted through a consistent and reproducible method to search, appraise, and summarize information. Within the evidence-based pyramid, systematic reviews can be at the apex when incorporating high-quality studies, presenting the strongest form of evidence given their synthesis of results from multiple primary studies to level IV evidence, depending on the studies they incorporate. When combined and supplemented with a meta-analysis using statistical methods to pool the results of three or more studies, systematic reviews are powerful tools to help answer research questions. The aim of this review is to serve as a guide on how to: 1) design; 2) execute; and 3) publish an orthopaedic arthroplasty systematic review and meta-analysis. In Part I, we discuss how to develop an appropriate research question as well as source and screen databases. To date, commonly used databases to source studies include PubMed/MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science. Although not all-encompassing, this paper serves as a starting point for those interested in performing and/or critically reviewing lower extremity arthroplasty systematic reviews and meta-analyses.

Risk Factors for Readmission Following Surgical Decompression for Spinal Epidural Abscesses: An Analysis of 4595 Patients.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The study aimed to (1) compare baseline demographics of patients undergoing surgery for SEA who were/were not readmitted; (2) identify risk factors for 90-day readmissions; and (3) quantify 90-day episode-of-care health care costs. BACKGROUND: Spinal epidural abscess (SEA), while rare, occurring ~2.5-5.1/10,000 admissions, may lead to permanent neurologic deficits and mortality. Definitive treatment often involves surgical intervention via decompression. METHODS: A search of the PearlDiver database from 2010 to 2021 for patients undergoing decompression for SEA identified 4595 patients. Cohorts were identified through the International Classification of Disease, Ninth Revision (ICD-9), ICD-10, and Current Procedural Terminology codes. Baseline demographics of patients who were/were not readmitted within 90 days following decompression were aggregated/compared, identifying factors associated with readmission. Using Bonferroni correction, a P-value<0.001 was considered statistically significant. RESULTS: Readmission within 90 days of surgical decompression occurred in 36.1% (1659/4595) of patients. While age/gender were not associated with readmission rate, alcohol use disorder, arrhythmia, chronic kidney disease, ischemic heart disease, and obesity were associated with readmission. Readmission risk factors included fluid/electrolyte abnormalities, obesity, paralysis, tobacco use, and pathologic weight loss (P<0.0001). Mean same-day total costs ($17,920 vs. $8204, P<0.001) and mean 90-day costs ($46,050 vs. $15,200, P<0.001) were significantly higher in the readmission group. CONCLUSION: A substantial proportion of patients (36.1%) are readmitted within 90 days following surgical decompression for SEA. The top 5 risk factors in descending order are fluid/electrolyte abnormalities, pathologic weight loss, tobacco use, pre-existing paralysis, and obesity. This study highlights areas for perioperative medical optimization that may reduce health care utilization.

Dietary Intakes of Long-Chain Polyunsaturated Fatty Acids and Impulsivity: Comparing Non-Restricted, Vegetarian, and Vegan Diets.

BACKGROUND: Research suggests a link between deficiencies in omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) and impulsivity among psychiatric populations. However, this association is less evident in non-clinical populations. As omega-3 LCPUFAs are predominantly sourced through fish consumption, non-fish dieters may be more vulnerable to higher impulsivity. METHODS: This cross-sectional observational study explored the association between lower intakes of omega-3 LCPUFA food sources and higher self-reported measures of impulsivity among healthy adults consuming non-restricted, vegetarian, and vegan diets. RESULTS: The results from the validated Food Frequency Questionnaire showed significantly lower estimated omega-3 LCPUFA intakes among vegans and vegetarians when compared with people consuming non-restricted diets. Furthermore, although all groups scored within the normal range of impulsivity measures, vegans scored comparatively higher. Vegans also scored significantly higher in impulsivity control relating to attention than those consuming non-restricted diets. CONCLUSIONS: The significantly lower omega-3 LCPUFA dietary intakes in the vegan diets were associated with higher scores in the second-order attentional aspect of self-reported impulsiveness.

How-To Create an Orthopaedic Systematic Review: A Step-by-Step Guide. Part III: Executing a Meta-Analysis.

At the top of the evidence-based pyramid, systematic reviews stand out as the most powerful, synthesizing findings from numerous primary studies. Specifically, a quantitative systematic review, known as a meta-analysis, combines results from various studies to address a specific research question. This review serves as a guide on how to: (1) design; (2) perform; and (3) publish an orthopedic arthroplasty systematic review. In Part III, we focus on how to design and perform a meta-analysis. We delineate the advantages and disadvantages of meta-analyses compared to systematic reviews, acknowledging their potential challenges due to time constraints and the complexities posed by study heterogeneity and data availability. Despite these obstacles, a well-executed meta-analysis contributes precision and heightened statistical power, standing at the apex of the evidence-based pyramid. The design of a meta-analysis closely mirrors that of a systematic review, but necessitates the inclusion of effect sizes, variability measures, sample sizes, outcome measures, and overall study characteristics. Effective data presentation involves the use of forest plots, along with analyses for heterogeneities and subgroups. Widely-used software tools are common in this domain, and there is a growing trend toward incorporating artificial intelligence software. Ultimately, the intention is for these papers to act as foundational resources for individuals interested in conducting systematic reviews and meta-analyses in the context of orthopaedic arthroplasty, where applicable.

ChatGPT as a Source of Patient Information for Lumbar Spinal Fusion and Laminectomy: A Comparative Analysis Against Google Web Search.

STUDY DESIGN: Retrospective Observational Study. OBJECTIVE: The objective of this study was to assess the utility of ChatGPT, an artificial intelligence chatbot, in providing patient information for lumbar spinal fusion and lumbar laminectomy in comparison with the Google search engine. SUMMARY OF BACKGROUND DATA: ChatGPT, an artificial intelligence chatbot with seemingly unlimited functionality, may present an alternative to a Google web search for patients seeking information about medical questions. With widespread misinformation and suboptimal quality of online health information, it is imperative to assess ChatGPT as a resource for this purpose. METHODS: The first 10 frequently asked questions (FAQs) related to the search terms "lumbar spinal fusion" and "lumbar laminectomy" were extracted from Google and ChatGPT. Responses to shared questions were compared regarding length and readability, using the Flesch Reading Ease score and Flesch-Kincaid Grade Level. Numerical FAQs from Google were replicated in ChatGPT. RESULTS: Two of 10 (20%) questions for both lumbar spinal fusion and lumbar laminectomy were asked similarly between ChatGPT and Google. Compared with Google, ChatGPT's responses were lengthier (340.0 vs. 159.3 words) and of lower readability (Flesch Reading Ease score: 34.0 vs. 58.2; Flesch-Kincaid grade level: 11.6 vs. 8.8). Subjectively, we evaluated these responses to be accurate and adequately nonspecific. Each response concluded with a recommendation to discuss further with a health care provider. Over half of the numerical questions from Google produced a varying or nonnumerical response in ChatGPT. CONCLUSIONS: FAQs and responses regarding lumbar spinal fusion and lumbar laminectomy were highly variable between Google and ChatGPT. While ChatGPT may be able to produce relatively accurate responses in select questions, its role remains as a supplement or starting point to a consultation with a physician, not as a replacement, and should be taken with caution until its functionality can be validated.

The real time to surgery: Limited delay after medical optimization does not impact hip fracture surgery outcomes.

INTRODUCTION: Current U.S./Canadian guidelines recommend hip fracture surgery within 48 h of injury to decrease morbidity/mortality. Multiple studies have identified medical optimization as the key component of time to surgery, but have inherent bias as patients with multiple co-morbidities often take longer to optimize. This study aimed to evaluate time from medical optimization to surgery (TMOS) to determine if "real surgical delay" is associated with: 1) mortality and 2) complications for geriatric hip fracture patients. METHODS: A retrospective chart review of geriatric hip fractures treated from 2015-2018 at a single, level-1 trauma center was conducted. Univariate logistic regression was performed to identify association between TMOS and post-operative complication rates. For mortality, the Wilcoxon test was used to compare TMOS for patients discharged following surgery to those who were not. RESULTS: A total of 884 hip fractures were treated operatively, with median TMOS 16.2 h (5.0-22.5, 1st-3rd quartiles). Univariate logistic regression models did not identify an association between TMOS and complication rates. For patients successfully discharged, median TMOS was 16.2 h (5.0-22.3, 1st-3rd quartiles). For the cohort of patients not successfully discharged, median TMOS was 19.1 h (10.1-25.9, 1st-3rd quartiles, p = 0.16). CONCLUSION: "Real surgical delay", or TMOS is not associated with increased complications or with inpatient mortality for geriatric hip fracture patients. With few exceptions, our institution adhered to the 48-hour time window from injury to hip surgery. We maintain the belief timely surgery following optimization plays a crucial role in the geriatric hip fracture patient outcomes.

Market resilience of orthopaedic hip/knee arthroplasty sales during COVID-19.

INTRODUCTION: The coronavirus 2019 (COVID-19) pandemic led to a marked decrease in elective surgical volume and orthopaedic device sales. The aim of this paper was to quantify this decrease and the related financial impact on the largest hip/knee arthroplasty companies by: (1) tracking individual hip/knee company valuations; (2) calculating aggregate changes in overall hip/knee arthroplasty market valuations; and (3) quantifying quarterly hip/knee revenues relative to prior years. MATERIALS AND METHODS: Financial data on the top five hip/knee arthroplasty companies by size between January 1, 2019, and October 1, 2020, was collected from a Wall Street financial database, S&P Capital IQ. Changes in valuation of these companies were compared against benchmark market indices, the S&P500 and Vanguard Healthcare ETF. U.S. hip/knee arthroplasty-specific revenue for Q1 and Q2 of 2019 and 2020 was collected from Securities Exchange Commission 10-Q forms. Quarterly revenue changes were calculated using 1-2Q19 revenues as baselines and aggregate to approximate the overall hip/knee arthroplasty market. RESULTS: The top five hip/knee companies lost $179.2 billion (32.7% loss) in market value from pre COVID-19 market highs to COVID-19 market lows (March 2020), while S&P500 and Vanguard Healthcare ETF decreased 36.1 and 33.2%, respectively. From market lows to October 2020, arthroplasty companies rallied 38.6% while the S&P500 and Vanguard Healthcare ETF regained 43.5 and 56.4% respectively. Notably, this occurred while aggregate 1Q/2Q20 revenue lagged 7.1/41.8% relative to 2019, with an overall decrease of $1.58B (24.8%). CONCLUSIONS: Similar to the overall market and healthcare sector, the top five hip/knee arthroplasty companies have recovered from their COVID market lows. Our results reveal that the valuations of hip/knee companies remained robust during COVID, even as revenues fell, likely due to strong investor confidence in the industry outlook and the greater overall healthcare system utilization.

Preoperative Depression Screening for Primary Total Knee Arthroplasty: An Evaluation of Its Modifiability on Outcomes in Patients Who Have Depression.

INTRODUCTION: Few studies have evaluated preoperative depression screenings in patients who have depression. We studied whether depression screenings before total knee arthroplasty (TKA) were associated with lower: 1) medical complications; 2) emergency department (ED) utilizations and readmissions; 3) implant complications; and 4) costs. METHODS: A nationwide sample from January 1, 2010 to April 30, 2021 was collected using an insurance database. Depression patients were 1:1 propensity-score matched based on those who had (n=29,009) and did not have (n=29,009) pre-operative depression screenings or psychotherapy visits within 3 months of TKA. A case-matched population who did not have depression was compared (n=144,994). A 90-day period was used to compare complications and healthcare utilization and 2-year follow-up for periprosthetic joint infections (PJIs) and implant survivorship. Costs were 90-day reimbursements. Logistic regression models computed odds ratios (OR) of depression screening on dependent variables. P-values less than 0.001 were significant. RESULTS: Patients who did not receive preoperative screening were associated with higher medical complications (18.7 versus 5.2%, OR:4.15, P < 0.0001) and ED utilizations (11.5 versus 3.2%, OR: 3.93, P < 0.0001) than depressed patients who received screening. Patients who had screening had lower medical complications (5.2 versus 5.9%, OR: 0.88, P < 0.0001) and ED utilizations compared to patients who did not have depression (3.2 versus 3.8%, OR: 0.87, P = 0.0001). Two-year PJI incidences (3.0 versus 1.3%, OR: 2.63, P < 0.0001) and TKA revisions (4.3 versus 2.1%, OR: 2.46, P < 0.0001) were greater in depression patients who were not screened preoperatively versus screened patients. Depression patients who had screening had lower PJIs (1.3 versus 1.8%, OR: 0.74, P < 0.0001) compared to non-depressed patients. Reimbursements ($13,949 versus $11,982; P < 0.0001) were higher in depression patients who did not have screening. CONCLUSIONS: Pre-operative screening was associated with improved outcomes in depression patients.

Blood-based biomarkers of cerebral small vessel disease.

Age-associated cerebral small vessel disease (CSVD) represents a clinically heterogenous condition, arising from diverse microvascular mechanisms. These lead to chronic cerebrovascular dysfunction and carry a substantial risk of subsequent stroke and vascular cognitive impairment in aging populations. Owing to advances in neuroimaging, in vivo visualization of cerebral vasculature abnormities and detection of CSVD, including lacunes, microinfarcts, microbleeds and white matter lesions, is now possible, but remains a resource-, skills- and time-intensive approach. As a result, there has been a recent proliferation of blood-based biomarker studies for CSVD aimed at developing accessible screening tools for early detection and risk stratification. However, a good understanding of the pathophysiological processes underpinning CSVD is needed to identify and assess clinically useful biomarkers. Here, we provide an overview of processes associated with CSVD pathogenesis, including endothelial injury and dysfunction, neuroinflammation, oxidative stress, perivascular neuronal damage as well as cardiovascular dysfunction. Then, we review clinical studies of the key biomolecules involved in the aforementioned processes. Lastly, we outline future trends and directions for CSVD biomarker discovery and clinical validation.

Serum Placental Growth Factor as a Marker of Cerebrovascular Disease Burden in Alzheimer's Disease.

BACKGROUND: Concomitant cerebrovascular diseases (CeVD) have been identified as an important determinant of Alzheimer's disease (AD) progression. Development of robust blood-based biomarkers will provide critical tools to evaluate prognosis and potential interventional strategies for AD with CeVD. OBJECTIVE: This study investigated circulating placental growth factor (PlGF), a potent pro-angiogenic factor related to endothelial dysfunction and vascular inflammation, in an Asian memory clinic cohort of non-demented individuals as well as AD, including its associations with neuroimaging markers of CeVD. METHODS: 109 patients with AD, 76 cognitively impaired with no dementia (CIND), and 56 non-cognitively impaired (NCI) were included in this cross-sectional study. All subjects underwent 3T brain magnetic resonance imaging to assess white matter hyperintensities (WMH), lacunes, cortical infarcts, and cerebral microbleeds (CMBs). Serum PlGF concentrations were measured by electrochemiluminescence immunoassays. RESULTS: Serum PlGF was elevated in AD, but not CIND, compared to the NCI controls. Adjusted concentrations of PlGF were associated with AD only in the presence of significant CeVD. Elevated PlGF was significantly associated with higher burden of WMH and with CMBs in AD patients. CONCLUSIONS: Serum PlGF has potential utility as a biomarker for the presence of CeVD, specifically WMH and CMBs, in AD. Further studies are needed to elucidate the underlying pathophysiological mechanisms linking PlGF to CeVD, as well as to further assess PlGF's clinical utility.

Serum Brevican as a Biomarker of Cerebrovascular Disease in an Elderly Cognitively Impaired Cohort.

In the brain, the extracellular matrix (ECM) composition shapes the neuronal microenvironment and can undergo substantial changes with cerebral pathology. Brevican is integral to the formation of the ECM's neuroprotective perineuronal nets (PNNs). Decreased brevican levels were reported in vascular dementia (VaD) but not in Alzheimer's disease (AD). However, the status of brevican in clinical cohorts with high concomitance of AD pathological burden and cerebrovascular disease (CeVD) is unclear. In this study, 32 non-cognitively impaired (NCI), 97 cognitively impaired no dementia (CIND), 46 AD, and 23 VaD participants recruited from memory clinics based in Singapore underwent neuropsychological and neuroimaging assessments, together with measurements of serum brevican. Association analyses were performed between serum brevican and neuroimaging measures of CeVDs, including white matter hyperintensities (WMHs), lacunes, cortical infarcts, and cerebral microbleeds. Using an aggregated score for CeVD burden, only CIND participants showed lower brevican levels with higher CeVD compared to those with lower CeVD burden (p = 0.006). Among the CeVD subtypes assessed, only elevated WMH burden was associated with lower brevican levels (OR = 2.7; 95% CI = 1.3-5.5). Our findings suggest that brevican deficits may play a role in early cerebrovascular damage in participants at risk of developing dementia.

Sequence analysis of Discoknowium, an A5 mycobacteriophage.

Discoknowium is a temperate A5 bacteriophage that infects the bacterial host Mycobacterium smegmatis. Isolated from a rat fecal sample, Discoknowium's genome is 50,222 bp in length, contains 84 genes and 1 tRNA, and shares 82%-98% nucleotide identity with other A5 subcluster phages.