Plasma proteome profiling in giant cell arteritis.

OBJECTIVES: This study aimed to identify plasma proteomic signatures that differentiate active and inactive giant cell arteritis (GCA) from non-disease controls. By comprehensively profiling the plasma proteome of both patients with GCA and controls, we aimed to identify plasma proteins that (1) distinguish patients from controls and (2) associate with disease activity in GCA. METHODS: Plasma samples were obtained from 30 patients with GCA in a multi-institutional, prospective longitudinal study: one captured during active disease and another while in clinical remission. Samples from 30 age-matched/sex-matched/race-matched non-disease controls were also collected. A high-throughput, aptamer-based proteomics assay, which examines over 7000 protein features, was used to generate plasma proteome profiles from study participants. RESULTS: After adjusting for potential confounders, we identified 537 proteins differentially abundant between active GCA and controls, and 781 between inactive GCA and controls. These proteins suggest distinct immune responses, metabolic pathways and potentially novel physiological processes involved in each disease state. Additionally, we found 16 proteins associated with disease activity in patients with active GCA. Random forest models trained on the plasma proteome profiles accurately differentiated active and inactive GCA groups from controls (95.0% and 98.3% in 10-fold cross-validation, respectively). However, plasma proteins alone provided limited ability to distinguish between active and inactive disease states within the same patients. CONCLUSIONS: This comprehensive analysis of the plasma proteome in GCA suggests that blood protein signatures integrated with machine learning hold promise for discovering multiplex biomarkers for GCA.

Update on Atypical Femoral Fractures.

➤ Atypical femoral fractures (AFFs) are stress fractures between the lesser trochanter and the metaphyseal flare that are most commonly related to prolonged (3 to 5 years) antiresorptive medication use.➤ An important finding is a visible transverse line in the lateral cortex, known as the "dreaded black line." Complete fractures are transverse and have minimal comminution.➤ Prodromal symptoms including hip, groin, thigh, and knee pain are present in more than one-half of cases and are usually misdiagnosed.➤ Nonoperative treatment for all patients with AFF includes withdrawal of bisphosphonates, assessment for secondary causes of osteoporosis, and optimization of vitamin D and calcium.➤ Incomplete fractures without a visible line can initially be treated nonoperatively with protected weight-bearing.➤ Intramedullary nailing is indicated for complete fractures and incomplete fractures with a visible fracture line. Delayed healing after fixation should be anticipated.➤ Treatment with parathyroid hormone (PTH) analogs (teriparatide and abaloparatide) after AFF prevents other fractures in high-risk patients, but the effect on healing of the fracture is unclear.

From formulation to structure: 3D electron diffraction for the structure solution of a new indomethacin polymorph from an amorphous solid dispersion.

3D electron diffraction (3DED) is increasingly employed to determine molecular and crystal structures from micro-crystals. Indomethacin is a well known, marketed, small-molecule non-steroidal anti-inflammatory drug with eight known polymorphic forms, of which four structures have been elucidated to date. Using 3DED, we determined the structure of a new ninth polymorph, σ, found within an amorphous solid dispersion, a product formulation sometimes used for active pharmaceutical ingredients with poor aqueous solubility. Subsequently, we found that σ indomethacin can be produced from direct solvent evaporation using dichloromethane. These results demonstrate the relevance of 3DED within drug development to directly probe product formulations.

The Impact of Spine Injuries on Amateur Athletes: An Exploratory Analysis of Sport-Related Patient-Reported Outcomes.

INTRODUCTION: There is a lack of information on return to sport and patient-reported outcome measures (PROMs) in amateur athletes after isolated spine injuries. METHODS: A single-center cohort study in amateur athletes aged 18 to 60 with isolated spine injuries; clinical data collection and follow-up via telephone interview and standardized PROMs (Short-Form 36, Oswestry and Neck Disability Index, Tampa Scale of Kinesiophobia, Hospital Anxiety and Depression Scale, Pain Visual Analog Scale). Bivariate analyses of potential influencing factors on PROMs were conducted using the Wilcoxon Signed-Rank Test. p-values < 0.05 were considered statistically significant. RESULTS: Out of the 80 included participants, 78% (n = 62) were active in sport at follow-up. PROMs were slightly worse than those described for the age-adjusted general population. There were consistent associations of better PROMs with having reached the subjective preinjury level of performance in sport, while injury severity and surgical or conservative therapy did not show consistent associations with PROMs. CONCLUSION: Most amateur athletes resume their sports activity after a spine injury. Better outcomes are associated with individuals' resumption of sport and subjective level of performance, while injury severity and surgical or conservative therapy do not show consistent associations with PROMs, highlighting the importance of patient education, rehabilitation, and encouragement.

The impact of telemonitoring on correct drug use, complications and quality of life among patients with multiple myeloma (ITUMM): A study protocol for an open-label, parallel-group, randomized controlled trial.

INTRODUCTION: Multiple myeloma (MM) is the second most common hematologic malignancy. MM is associated with significant morbidity due to its end-organ destruction and is a disease of the older population. Although survival rates for MM have improved over the last decade, due to an increase in treatment options, the disease remains incurable. Expensive (oral) agents are widely used in MM patients; however, tools for supporting patients in complex treatment regimens are scarce. To investigate if a tool will support MM patients and healthcare professionals, the MM e-coach was developed and tested. The aim of this study is to study the impact of telemonitoring on adherence, complications and quality of life in patients with MM (ITUMM study). METHODS: A two-arm open-label parallel-group randomized controlled trial will be conducted between March 2021 and June 2024 to compare the telemonitoring (MM e-coach) with standard MM care. This study aimed to recruit 150 patients with recently diagnosed multiple myeloma (RDMM), starting first or second line of treatment. Blinded primary outcome is adherence by pill count after start of treatment at 1-3 months. Secondary outcomes are patient reported outcomes: GFI, EQ-5D-5L, EORTC-QLQ-C30, SDM-Q-9, MARS-5, single item questions, PREMs, adverse events, OS and PFS. Patient reported outcomes were developed and integrated in the e-coach MM to regularly measure digitized outcomes of MM patients from time of RDMM until 12 months post-diagnosis. Online measurements will be performed at baseline (0), 3, 6, 9 and 12 months. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Ethics Committee of the Isala klinieken in The Netherlands (No. 201111) at 25 February 2021. Study results will be disseminated to the relevant healthcare communities by publication in peer-reviewed journals, and at scientific and clinical conferences. STUDY REGISTRATION NUMBER: ClinicalTrials.gov number: NCT05964270 and ABR number: NL75771.075.20.

Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort.

BACKGROUND: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To investigate clinical laboratory markers of SARS-CoV-2 and PASC. DESIGN: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024). SETTING: 83 enrolling sites. PARTICIPANTS: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection. MEASUREMENTS: Participants completed questionnaires and standard clinical laboratory tests. RESULTS: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero. LIMITATION: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined. CONCLUSION: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC. PRIMARY FUNDING SOURCE: National Institutes of Health.

Effect of estradiol with or without micronized progesterone on cholinergic-related cognitive performance in postmenopausal women.

Introduction: Women are at a higher risk of developing Alzheimer's disease (AD), and the decline in estrogens post-menopause is thought of as a factor increasing this risk. Estradiol (E2) is important in supporting cholinergic neuronal integrity, and cholinergic functioning may be negatively impacted following the loss of E2 post-menopause. The use of exogenous E2 has been observed to enhance cholinergically mediated cognitive performance in healthy post-menopausal women, which indicates a potentially protective mechanism. However, E2 is often co-administered with progestin or progesterone to prevent endometrial proliferation. Progesterone/progestins have previously been shown to have a detrimental effect on E2-mediated biological and cognitive effects mediated by cholinergic systems in preclinical models, therefore the present study aimed to assess whether progesterone would modify the effect of E2 to influence cognition during cholinergic blockade. Methods: Twenty participants completed 3-months of oral E2 treatment with micronized progesterone (mPRO) or with placebo (PLC) in a repeated-measures within-subjects crossover design, in which they also completed five anticholinergic challenge days per hormone treatment condition. During the challenge participants were administered low or high doses of the nicotinic cholinergic antagonist mecamylamine, the muscarinic cholinergic antagonist scopolamine, or placebo. Following drug administration participants performed cognitive tests sensitive to cholinergic tone, assessing attention, episodic memory, and working memory. Results: Significant decrements were found on some tasks when participants were taking E2+mPRO compared to E2 alone. Specifically, under more challenging task conditions and larger anticholinergic doses, participants showed poorer performance on the Critical Flicker Fusion task and the Stroop test and responded more conservatively on the N-back working memory task. Other tasks showed no differences between treatments under cholinergic blockade. Discussion: The findings show that mPRO when taken in concert with E2, was detrimental to effortful cognitive performance, in the presence of cholinergic blockade. These results are important for assessing the impact of combined postmenopausal hormone treatment on cognitive performance that is dependent on cholinergic functioning after menopause.

Modulation of the pharmacokinetics of soluble ACE2 decoy receptors through glycosylation.

The Spike of SARS-CoV-2 recognizes a transmembrane protease, angiotensin-converting enzyme 2 (ACE2), on host cells to initiate infection. Soluble derivatives of ACE2, in which Spike affinity is enhanced and the protein is fused to Fc of an immunoglobulin, are potent decoy receptors that reduce disease in animal models of COVID-19. Mutations were introduced into an ACE2 decoy receptor, including adding custom N-glycosylation sites and a cavity-filling substitution together with Fc modifications, which increased the decoy's catalytic activity and provided small to moderate enhancements of pharmacokinetics following intravenous and subcutaneous administration in humanized FcRn mice. Most prominently, sialylation of native glycans increases exposures by orders of magnitude, and the optimized decoy is therapeutically efficacious in a mouse COVID-19 model. Ultimately, an engineered and highly sialylated decoy receptor produced using methods suitable for manufacture of representative drug substance has high exposure with a 5- to 9-day half-life. Finally, peptide epitopes at mutated sites in the decoys generally have low binding to common HLA class II alleles and the predicted immunogenicity risk is low. Overall, glycosylation is a critical molecular attribute of ACE2 decoy receptors and modifications that combine tighter blocking of Spike with enhanced pharmacokinetics elevate this class of molecules as viable drug candidates.

Changes in Left Ventricular Function and Outcomes After Trancatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

Background: Transcatheter edge-to-edge repair (TEER) improved outcomes in patients with heart failure (HF) and severe secondary mitral regurgitation (SMR) compared with guideline-directed medical therapy (GDMT) alone regardless of the severity of baseline left ventricular ejection fraction (LVEF). The study aimed to evaluate the effect of early changes in LVEF after TEER and GDMT alone in patients with HF and severe SMR. Methods: Within the COAPT trial, we evaluated outcomes according to changes in LVEF from baseline to 30 days. The primary outcome was all-cause death or HF hospitalization (HFH) between 30 days and 2 years. Results: Among 432 patients with paired echocardiographic data, 182 (42.1%) had increased LVEF (LVEF change 6.0% ± 4.9%) and 250 (57.9%) had a decrease or no change in LVEF (LVEF change -6.6% ± 5.6%) from baseline to 30 days. LVEF at 30 days increased more frequently with GDMT alone compared with TEER plus GDMT (51.4% vs 33.0%; P = .0001). Between 30 days and 2 years, there were no significant differences in death or HFH in the increase LVEF and the decrease LVEF groups (58.8% vs 51.4%; multivariable-adjusted HR, 0.97; 95% CI, 0.87-1.08; P = .59). TEER plus GDMT reduced the 30-day to 2-year rate of death or HFH compared with GDMT alone consistently in patients with increase LVEF and decrease LVEF (Pint = 0.75). Conclusions: Among patients with HF and severe SMR, early improvements in LVEF were more frequent with GDMT alone compared with TEER plus GDMT but were not associated with subsequent outcomes at 2 years. TEER reduced death or HFH during 2-year follow-up irrespective of early LVEF changes.

How recovery definitions vary by service use pathway: Findings from a national survey of adults.

OBJECTIVE: How people define recovery may affect their recovery goals, service use, and ultimately their outcomes. We examined recovery definitions among adults in recovery from an alcohol use disorder (AUD) who had different service use histories. METHOD: We analyzed online survey data from 1,492 adults with resolved lifetime AUD in "treated recovery" (any use of specialty services, such as inpatient or outpatient rehabilitation; n = 375), "assisted recovery" (any use of lay services, such as mutual-help groups, and no use of specialty services; n = 174), or "independent recovery" (no use of specialty or lay services; n = 943). Surveys assessed recovery definitions using the 39-item What Is Recovery? (WIR) scale. We compared endorsement of WIR domains and individual recovery elements across groups using survey-weighted chi-square tests and logistic regression. RESULTS: Endorsement of WIR scale domains was significantly lower among the independent than treated and assisted groups, but few differences emerged between the treated and assisted groups. Two recovery elements were endorsed by approximately equivalent majorities of all groups: "being honest with myself" (92.7%-94.8%) and "taking care of my physical health" (87.4%-90.9%). Five additional elements were similarly endorsed by large majorities (≥ 85%) in each group, albeit at lower levels in the independent group. CONCLUSIONS: People who have experienced AUD and have not obtained alcohol services may have a narrower definition of recovery compared to those accessing treatment or attending mutual-help groups. This suggests a need to broaden alcohol services to better match varied recovery definitions; however, some highly endorsed elements suggest commonalities across recovery pathways. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinical Characteristics of Charcot-Marie-Tooth Disease Type 4J.

BACKGROUND AND OBJECTIVES: Charcot-Marie-Tooth disease type 4J (CMT4J) is caused by autosomal recessive variants in the Factor-Induced Gene 4 (FIG4) gene. Recent preclinical work has demonstrated the feasibility of adeno-associated virus serotype 9-FIG4 gene therapy. This study aimed to further characterize the CMT4J phenotype and evaluate feasibility of validated CMT-related outcome measures for future clinical trials. METHODS: This cross-sectional study enrolled children and adults with genetically confirmed CMT4J, with 2 documented disease-causing variants in the FIG4 gene. Patients were recruited through the Inherited Neuropathy Consortium network. Disease severity was assessed using standardized CMT-specific outcome measures and exploratory biomarkers including muscle MRI fat fraction, electrophysiology, and neurofilament light chain levels. Descriptive statistics and correlation analyses were conducted to explore relationships between variables. RESULTS: We recruited a total of 19 patients, including 14 pediatric patients (mean age 10.9 ± 3.9 years) and 5 adults (mean age 40.0 ± 13.9 years). The most frequent symptoms were gross motor delay and distal more than proximal muscle weakness, which were observed in 14 of 19 patients. The most common non-neuromuscular symptoms were cognitive and respiratory deficits, each seen in 8 of 19 patients. We denoted asymmetric weakness in 2 patients and nonuniform slowing of conduction velocities in 6 patients. Charcot-Marie-Tooth Disease Pediatric Scale (CMTPedS), Pediatric Quality of Life Inventory, and Vineland Adaptive Behavior Scale scores were affected in most patients. We observed a significant positive correlation between neurofilament light chain levels and CMTPedS, but the study was underpowered to observe a correlation between CMTPedS and MRI fat fraction. DISCUSSION: We obtained baseline clinical and biomarker data in a broad cohort with CMT4J in pediatric and adult patients. Motor delay, muscle weakness, and respiratory and cognitive difficulties were the most common clinical manifestations of CMT4J. Many patients had nerve conduction studies with nonuniform slowing, and 2 had an asymmetric pattern of muscle weakness. We observed that the neurofilament light chain levels correlated with the CMTPedS in the pediatric population. This study showed feasibility of clinical outcomes including CMTPedS in assessment of disease severity in the pediatric patient population and provided baseline characteristics of exploratory biomarkers, neurofilament light chain levels, and muscle MRI fat fraction. The coronavirus disease 2019 pandemic affected some of the visits, resulting in a reduced number of some of the assessments.

Empowering the biomedical research community: Innovative SAS deployment on the All of Us Researcher Workbench.

OBJECTIVES: The All of Us Research Program is a precision medicine initiative aimed at establishing a vast, diverse biomedical database accessible through a cloud-based data analysis platform, the Researcher Workbench (RW). Our goal was to empower the research community by co-designing the implementation of SAS in the RW alongside researchers to enable broader use of All of Us data. MATERIALS AND METHODS: Researchers from various fields and with different SAS experience levels participated in co-designing the SAS implementation through user experience interviews. RESULTS: Feedback and lessons learned from user testing informed the final design of the SAS application. DISCUSSION: The co-design approach is critical for reducing technical barriers, broadening All of Us data use, and enhancing the user experience for data analysis on the RW. CONCLUSION: Our co-design approach successfully tailored the implementation of the SAS application to researchers' needs. This approach may inform future software implementations on the RW.

Is more care recipient time at home also a family caregiver-centered quality of life measure?

BACKGROUND: Time in healthcare facilities is associated with worse patient quality of life (QoL); however, impact on family caregiver QoL is unknown. We evaluate care recipient days not at home-days in the emergency department (ED), inpatient (IP) care, and post-acute care (PAC)-to understand how care recipient days not at home correspond to family caregiver QoL. METHODS: Secondary data were linked to care recipient utilization data. Elastic net machine learning models were used to evaluate the impact of a single day of utilization in each setting on binary QoL outcomes. We also compared composite weighted and unweighted "days not at home" variables. Two time periods, 6 and 18 months, were used to predict three caregiver QoL measures (self-rated health, depressive symptoms, and subjective burden). RESULTS: In the 6-month timeframe, a single day of ED utilization was associated with increased likelihood of poor QoL for all three assessed outcomes (range: 1.4%-3.2%). A day of PAC was associated to a modest degree with increased likelihood of caregiver burden (0.2%) and depressive symptoms (0.1%), with a slight protective effect for self-rated health (-0.1%). An IP day had a slight protective effect (-0.2 to -0.1%). At 18 months, ED and IP had similar, albeit more muted, relationships with caregiver burden and depressive symptoms. PAC had a slight protective effect for caregiver burden (-0.1%). Cumulative days in all settings combined generally was not associated with caregiver QoL. CONCLUSION: Whereas total care recipient time away from home had some negative spillovers to family caregivers, the countervailing effects of unique settings on caregiver QoL may mask net QoL effects. This finding limits the utility of a single care recipient home time measure as a valid caregiver-centered measure. Considering cumulative care recipient time in individual settings separately may be needed to reveal the true net effects on caregiver QoL.

The Influence of Nutrition Intervention on the P1NP and CTX-1 Response to an Acute Exercise Bout: A Systematic Review with Meta-Analysis.

BACKGROUND: Although nutrition and exercise both influence bone metabolism, little is currently known about their interaction, or whether nutritional intervention can modulate the bone biomarker response to acute exercise. Improved understanding of the relationships between nutrition, exercise and bone metabolism may have substantial potential to inform nutritional interventions to protect the bone health of exercising individuals, and to elucidate mechanisms by which exercise and nutrition influence bone. OBJECTIVE: The aim was to synthesise available evidence related to the influence of nutrition on the response of the bone biomarkers procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX-1) to acute exercise, using a systematic review and meta-analytic approach. METHODS: Studies evaluating the influence of nutritional status or intervention on the bone biomarker response to an acute exercise bout were included and separated into four categories: (1) feeding status and energy availability, (2) macronutrients, (3) micronutrients and (4) other. Studies conducted on healthy human populations of any age or training status were included. Meta-analysis was conducted when data from at least five studies with independent datasets were available. In the case of insufficient data to warrant meta-analysis, results from individual studies were narratively synthesised and standardised mean effect sizes visually represented. RESULTS: Twenty-two articles were included. Of these, three investigated feeding status or energy availability, eight macronutrients, eight micronutrients (all calcium) and six other interventions including dairy products or collagen supplementation. Three studies had more than one intervention and were included in all relevant outcomes. The largest and most commonly reported effects were for the bone resorption marker CTX-1. Meta-analysis indicated that calcium intake, whether provided via supplements, diet or infusion, reduced exercise-induced increases in CTX-1 (effect size - 1.1; 95% credible interval [CrI] - 2.2 to - 0.05), with substantially larger effects observed in studies that delivered calcium via direct infusion versus in supplements or foods. Narrative synthesis suggests that carbohydrate supplementation may support bone during acute exercise, via reducing exercise-induced increases in CTX-1. Conversely, a low-carbohydrate/high-fat diet appears to induce the opposite effect, as evidenced by an increased exercise associated CTX-1 response, and reduced P1NP response. Low energy availability may amplify the CTX-1 response to exercise, but it is unclear whether this is directly attributable to energy availability or to the lack of specific nutrients, such as carbohydrate. CONCLUSION: Nutritional intervention can modulate the acute bone biomarker response to exercise, which primarily manifests as an increase in bone resorption. Ensuring adequate attention to nutritional factors may be important to protect bone health of exercising individuals, with energy, carbohydrate and calcium availability particularly important to consider. Although a wide breadth of data were available for this evidence synthesis, there was substantial heterogeneity in relation to design and intervention characteristics. Direct and indirect replication is required to confirm key findings and to generate better estimates of true effect sizes.

2024 Update to the 2020 ACC/AHA Clinical Performance and Quality Measures for Adults With Heart Failure: A Report of the American Heart Association/American College of Cardiology Joint Committee on Performance Measures.

This document describes performance measures for heart failure that are appropriate for public reporting or pay-for-performance programs and is meant to serve as a focused update of the "2020 ACC/AHA Clinical Performance and Quality Measures for Adults With Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures." The new performance measures are taken from the "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines" and are selected from the strongest recommendations (Class 1 or Class 3). In contrast, quality measures may not have as much evidence base and generally comprise metrics that might be useful for clinicians and health care organizations for quality improvement but are not yet appropriate for public reporting or pay-for-performance programs. New performance measures include optimal blood pressure control in patients with heart failure with preserved ejection fraction, the use of sodium-glucose cotransporter-2 inhibitors for patients with heart failure with reduced ejection fraction, and the use of guideline-directed medical therapy in hospitalized patients. New quality measures include the use of sodium-glucose cotransporter-2 inhibitors in patients with heart failure with mildly reduced and preserved ejection fraction, the optimization of guideline-directed medical therapy prior to intervention for chronic secondary severe mitral regurgitation, continuation of guideline-directed medical therapy for patients with heart failure with improved ejection fraction, identifying both known risks for cardiovascular disease and social determinants of health, patient-centered counseling regarding contraception and pregnancy risks for individuals with cardiomyopathy, and the need for a monoclonal protein screen to exclude light chain amyloidosis when interpreting a bone scintigraphy scan assessing for transthyretin cardiac amyloidosis.

New interest in fibrinogen as an ischemic risk factor.

Platelet-fibrin clot formation is a key process in acute arterial thrombosis. The relationship between thrombin-induced platelet-fibrin clot strength (P-FCS) and fibrinogen levels in patients with cardiovascular disease (CVD) and COVID-19 has not been studied. In thhe current study, the contribution of fibrinogen to P-FCS has been explored in healthy subjects (n=157), patients hospitalized with COVID-19 (n=116), and patients with CVD (n=93) using thrombelastography (TEG 6s) with citrate cartridge. We found that thrombin-induced P-FCS, fibrin clot strength (F-CS) and fibrinogen levels (FLEV) were higher among patients with CVD and COVID-19 compared to HS (p<0,05 for all) and highest among patients with COVID-19. P-FCS, an established risk factor for post-PCI ischemic event occurrences, was associated with both F-CS and FLEV (R2=0.67, p<0.001 for both comparisons. These data indicate that fibrinogen levels strongly influence the viscoelastic strength of the platelet-fibrin clot, fibrinogen may be an important driving factor for arterial thrombosis in the presence of potent platelet inhibition and may be as equally important a risk factor as high platelet reactivity. Since P-FCS is significantly associated with fibrinogen levels, the role of fibrinogen as a risk factor for arterial ischemic event occurrences should be further studied to improve antithrombotic therapy personalization.

Where should we go - Estimating travel times for modelling accessibility to 24-hour emergency departments in Canada.

Estimating travel time to 24-hour emergency services is an important component to modelling accessibility of health services, particularly for rural areas. However, methods used to estimate travel time vary significantly, are not representative of the residential population, and are not openly validated. This makes the assessment of travel-based accessibility metrics between studies incomparable. To address this issue and develop a standardized measurement of emergency service access, this study utilized small geographic units (Dissemination Areas - DA) and geographical boundaries representative of municipal equivalents (Census Subdivision - CSD). Estimated travel times between the centroid of an inhabited DA to each 24-hr emergency department was computed with population-weighted travel times generated for each CSD. This dataset provides a nationally consistent measurement of proximity to emergency services accounting for travel pathing and population distribution. This methodology can be extended to generate estimated shortest travel routes for other healthcare resources or develop actual travel routes based on individuals' experiences with the healthcare system.

Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after fecal microbiota transplant in inflammatory bowel disease.

Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.

Improved postural control in a patient having adult spinal deformity and previous thoraco-lumbar scoliosis surgery: a Chiropractic Biophysics® case report.

Background: There is evidence indicating patients with spinal deformity have impaired postural control and balance issues. Often, previous surgical intervention excludes the older patient from further invasive procedures leaving them with limited treatment options. The purpose of this case is to report on the clinically significant improvement in postural control as measured by force plate after a multimodal treatment program of Chiropractic Biophysics® (CBP®) posture rehabilitation as well as balance rehabilitation in an elderly patient with long-standing spinal deformity including thoracic hyperkyphosis and a T10-L4 Harrington rod instrumentation for thoracolumbar scoliosis. Case Description: A 69-year-old female presented with the main complaint of balance and gait impairment as well as back pain and headaches. Balance assessment on a force plate showed impaired balance, in the vestibular challenging condition (eyed closed; standing on foam). Radiography showed a forward stooped posture and surgical hardware. Treatment was directed at posture by CBP methods and balance rehabilitation by a whole-body vibration exercise program. Treatment progressed over a 10-month period. The patient experienced relief of back pains and headaches. There was a clinically significant improvement in posturography including a 102 cm reduction in center of pressure (COP) path length. There was an inch reduction in forward sagittal stoop. Conclusions: A non-surgical rehabilitation program demonstrated a clinically significant improvement in balance performance in an elderly female diagnosed with osteopenia, spinal deformity, and previous spine deformity surgery. This approach to improving postural stability is important and further investigations should be undertaken.