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2.
J Med Chem ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995734

ABSTRACT

Herein, we report the synthesis and biological evaluation of a novel series of heparinoid amphiphiles as inhibitors of heparanase and SARS-CoV-2. By employing a tailor-made synthetic strategy, a library of highly sulfated homo-oligosaccharides bearing d-glucose or a C5-epimer (i.e., l-idose or l-iduronic acid) conjugated with various lipophilic groups was synthesized and investigated for antiviral activity. Sulfated higher oligosaccharides of d-glucose or l-idose with lipophilic aglycones displayed potent anti-SARS-CoV-2 and antiheparanse activity, similar to or better than pixatimod (PG545), and were more potent than their isosteric l-iduronic acid congeners. Lipophilic groups such as cholestanol and C18-aliphatic substitution are more advantageous than functional group appended lipophilic moieties. These findings confirm that fine-tuning of higher oligosaccharides, degree of sulfation, and lipophilic groups can yield compounds with potent anti-SARS-CoV-2 activity.

3.
J Hand Microsurg ; 16(3): 100051, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39035862

ABSTRACT

Purpose: As stakeholders seek to improve patient outcomes while maintaining cost-effectiveness in an increasingly expensive healthcare system, metrics such as patient satisfaction are becoming more important. This present study sought to identify factors associated with and independently predictive of better surgical satisfaction two years following hand and wrist surgery. Methods: Patients undergoing hand and wrist surgery at an urban outpatient institution were enrolled preoperatively into a surgical registry and assessed two years postoperatively. Patient satisfaction with surgery was measured at two years postoperatively with the Surgical Satisfaction Questionnaire (SSQ-8). Bivariate analysis determined associations between postoperative satisfaction and patient demographics, injury specifiers, medical history, and multiple patient-reported outcomes (PROs). Multivariable analysis determined independent predictors of two-year postoperative satisfaction following hand and wrist surgery. Results: Better surgical satisfaction was associated with having never smoked, no preoperative opioid use, lack of an accompanying legal claim, lack of a workers compensation claim, no clinical history of depression/anxiety, less comorbidities, and higher preoperative expectations.Various PROs relating to function, pain, activity, and general health at both baseline and two years demonstrated associations with postoperative satisfaction. Multivariable analysis confirmed that never smoking, lack of a legal claim, and better preoperative Brief Michigan Hand Questionnaire scores were independently predictive of better surgical satisfaction two years following hand and wrist surgery. Conclusion: At two years following hand and wrist surgery, better patient satisfaction was best predicted by never smoking, no related legal claim, and better baseline Brief Michigan Hand Questionnaire scores. Level of evidence: III.

4.
J Hand Microsurg ; 16(3): 100060, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39035863

ABSTRACT

Introduction: Opioid overprescribing has caused a substantial increase in opioid related deaths and billions of dollars in additional healthcare costs. Orthopaedic surgeons commonly prescribe opioids in the perioperative period; however, research has shown preoperative opioid use may be associated with worse postoperative outcomes. Despite this body of evidence, there are few studies investigating the association between preoperative opioid use and two-year outcomes after hand surgery. Materials and methods: This study evaluated two-year postoperative patient-reported outcomes in patients who used opioids prior to hand surgery, and those who did not. Patients completed pre and postoperative questionnaires including Patient-Reported Outcomes Measurement Information System (PROMIS) domains, the Brief Michigan Hand Questionnaire (BMHQ), and other questionnaires related to pain, function, and satisfaction. 342 patients undergoing upper-extremity surgery were enrolled into a prospective orthopaedic surgery outcome registry, and 69.9% completed the follow-up surveys. Preoperative opioid use and its association to patient outcome scores was analyzed through bivariate analysis. Significant associations were further tested by multivariable analysis to determine independent predictors. Results: Preoperative opioid use was associated with worse two-year PROMIS Fatigue (p â€‹< â€‹.01), PROMIS Anxiety (p â€‹< â€‹.01), PROMIS Depression (p â€‹< â€‹.01), SSQ-8 (p â€‹= â€‹.01), BMHQ (p â€‹= â€‹.01), NPS Hand (p â€‹< â€‹.01) and MODEMS met expectations (p â€‹= â€‹.03). No significant differences were observed in patient-reported outcome change scores. Multivariable analysis demonstrated that preoperative opioid use was predictive of worse two-year PROMIS Fatigue (p â€‹< â€‹.01), PROMIS Anxiety (p â€‹< â€‹.01), PROMIS Depression (p â€‹= â€‹.02), BMHQ (p â€‹= â€‹.01), SSQ-8 (p â€‹< â€‹.01), NPS Hand (p â€‹= â€‹.02) and MODEMS met expectations (p â€‹< â€‹.01). Conclusion: Preoperative opioid use was associated with worse patient-reported outcomes two years after elective hand surgery. There was no significant difference in the improvement from baseline between the two groups. Clinically significant differences were observed in follow-up PROMIS Anxiety, BMHQ and NPS - Hand scores. Clinically significant change scores were noted in both groups for PROMIS PF, PROMIS PI, PROMIS SS, BMHQ, and NPS - Hand.

5.
Article in English | MEDLINE | ID: mdl-38960805

ABSTRACT

OBJECTIVE: To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective single-center cohort study. SETTING: University-affiliated tertiary care academic medical center. PARTICIPANTS: Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001). CONCLUSIONS: Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications.

7.
Sci Rep ; 14(1): 13221, 2024 06 08.
Article in English | MEDLINE | ID: mdl-38851807

ABSTRACT

In exploring nature's potential in addressing diabetes-related conditions, this study investigates the therapeutic capabilities of 3-formyl chromone derivatives. Utilizing in silico methodologies, we focus on 6-substituted 3-formyl chromone derivatives (1-16) to assess their therapeutic potential in treating diabetes. The research examined the formyl group at the chromone's C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO-LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of - 8.5 kcal mol-1. This result outperformed the affinity of the reference standard dapagliflozin (- 7.9 kcal mol-1) as well as two other compounds that target human IDE, namely vitexin (- 8.3 kcal mol-1) and myricetin (- 8.4 kcal mol-1). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein-ligand complex at the active site.


Subject(s)
Chromones , Hypoglycemic Agents , Molecular Docking Simulation , Chromones/chemistry , Chromones/pharmacology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Computer Simulation
8.
J Clin Med ; 13(12)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38930056

ABSTRACT

Given the high morbidity and mortality associated with cardiopulmonary arrest, there have been multiple trials aimed at better monitoring and augmenting coronary, cerebral, and systemic perfusion. This article aims to elucidate these interventions, first by detailing the physiology of cardiopulmonary resuscitation and the available tools for managing cardiopulmonary arrest, followed by an in-depth examination of the newest advances in the monitoring and delivery of advanced cardiac life support.

9.
Cell Rep Med ; 5(5): 101529, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38703765

ABSTRACT

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.


Subject(s)
Genome-Wide Association Study , Head , Neoplasms , Humans , Head/anatomy & histology , Neoplasms/genetics , Neoplasms/pathology , Female , Male , Polymorphism, Single Nucleotide/genetics , Genetic Variation , Organ Size/genetics , Signal Transduction/genetics , Adult , Genetic Predisposition to Disease
10.
Article in English | MEDLINE | ID: mdl-38745357

ABSTRACT

BACKGROUND: Trauma patients are at increased risk for venous thromboembolism events (VTE). The decision of when to initiate VTE chemoprophylaxis (VTEP) and with what agent remains controversial in patients with severe traumatic brain injury (TBI). METHODS: This comparative effectiveness study evaluated the impact of timing and agent for VTEP on outcomes for patients with severe TBI (AIS Head = 3,4, or 5). Data was collected at 35 Level 1 and 2 trauma centers from January 1, 2017 to June 1, 2022. Patients were placed into analysis cohorts: No VTEP, low-molecular weight heparin (LMWH) ≤ 48 hours, LMWH>48 hours, Heparin≤48 hours, Heparin>48 hours. Propensity score matching accounting for patient factors and injury characteristics was used with logistic regression modeling to evaluate in-hospital mortality, VTE events, and discharge disposition. Neurosurgical intervention after initiation of VTEP was used to evaluate extension of intracranial hemorrhage. RESULTS: Of 12,879 patients, 32% had no VTEP, 36% LMWH, and 32% Heparin. Overall mortality was 8.3% and lowest among patients receiving LMWH≤48 hours (4.1%). VTE rates were lower with use of LMWH (1.6 vs 4.5%, OR 2.98, 95% CI 1.40-6.34, p = 0.005) without increasing mortality or neurosurgical interventions. VTE rates were lower with early prophylaxis (2.0 vs 3.5%, OR 1.76, 95% CI 1.15-2.71, p = 0.01) without increasing mortality (p = 1.0). Early VTEP was associated with more non-fatal intracranial operations (p < 0.001). However, patients undergoing neurosurgical intervention after VTEP initiation had no difference in rates of mortality, withdrawal of care, or unfavorable discharge disposition (p = 0.7, p = 0.1, p = 0.5). CONCLUSIONS: In patients with severe TBI, LMWH usage was associated with lower VTE incidence without increasing mortality or neurosurgical interventions. Initiation of VTEP≤48 hours decreased VTE incidence and increased non-fatal neurosurgical interventions without affecting mortality. LMWH is the preferred VTEP agent for severe TBI, and initiation ≤48 hours should be considered in relation to these risks and benefits. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level III.

11.
Ann Thorac Surg ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38735511

ABSTRACT

BACKGROUND: We describe outcomes and management strategies for single-ventricle and bilaterally discontinuous pulmonary arteries (PAs) originating from bilateral ductus arteriosus. METHODS: We reviewed 22 patients with aforementioned anatomy and PA centralization from 1995 to 2023, excluding those with biventricular repair. RESULTS: Median age at centralization was 9 days (minimum-maximum, 0 days-2 years). Centralization was performed with systemic-to-pulmonary shunt (n =20 [91%]; 2 after bilateral ductal stents) or bidirectional cavopulmonary connection (n = 2 [9%]) using pericardial roll (n = 14 [64%]), patch-augmented direct anastomosis (n = 7 [32%]), and interposition graft (n = 1 [5%]) techniques. Concurrent total anomalous pulmonary venous connection (TAPVC, n = 11 [50%]) was associated with significantly inferior survival (P = .01). Five patients (23%) died at a median of 59 days (minimum-maximum, 6-257 days) after centralization, all with noncardiac TAPVC. At the latest follow-up for 17 survivors (median, 13.5 years; minimum-maximum, 0.5-25.1 years after centralization), 12 completed Fontan, 4 completed second-stage palliation, and 1 received a transplant before second-stage palliation. PA reintervention was required in 14 patients (64%), including 3 with reoperations independent of staged palliation. Echocardiography from baseline to before the second stage demonstrated branch PA growth with significantly increased diameters (left, P = .0006; right, P = .0002); z-scores significantly increased for right (P = .004) but not left (P = .11). CONCLUSIONS: Successful single-ventricle palliation is possible, although high risk, for patients with bilateral discontinuous ductal PAs. Early postcentralization mortality remains substantial, particularly with associated noncardiac TAPVC. Many require reintervention to maintain PA growth, typically concurrently with staged palliation.

12.
Liver Transpl ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38771635

ABSTRACT

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with significant morbidity and mortality. While liver transplantation is the definitive treatment, continuous terlipressin infusion for HRS-AKI may provide benefit and, as such, was assessed in a population composed of candidates for liver transplant (LT). Fifty hospitalized LT-eligible patients with HRS-AKI received a single bolus followed by continuous terlipressin infusion. Acute-on-chronic liver failure grade 3, serum creatinine (SCr)>5.0 mg/dL, or Model for End-Stage Liver Disease (MELD) ≥35 were exclusions. Fifty hospitalized patients who received midodrine and octreotide or norepinephrine for HRS-AKI served as a historical comparator cohort. Complete response (CR) was defined as a ≥30% decrease in SCr with end-of-treatment (EOT) SCr≤1.5, partial response as a ≥30% decrease in SCr with EOT SCr>1.5, and nonresponse as a <30% decrease in SCr. CR rate was significantly higher in the terlipressin cohort compared to the historical cohort (64% vs. 16%, p <0.001). Survival, while numerically higher in those who received terlipressin, was statistically similar (D30: 94% vs. 82%, p =0.12; D90: 78% vs. 68%, p =0.37). Renal replacement therapy (RRT) was more common among terlipressin NR than CR and PR (70% vs. 3% vs. 13%, p < 0.001). EOT MELD and SCr were significantly lower within terlipressin cohort (MELD: 19 vs. 25, SCr: 1.4 vs. 2.1 mg/dL, p <0.001). Sixteen of 40 terlipressin-treated patients received LT-alone (terlipressin CR in 10/16). One patient on terlipressin had a hypoxic respiratory failure that responded to diuretics; one possibly had drug-related rash. With continuous terlipressin infusion, a CR rate of 64% was observed with a favorable safety profile. Terlipressin use was associated with lower EOT MELD and SCr than the historical midodrine and octreotide/norepinephrine cohort; LT-alone was accomplished in a high proportion of complete terlipressin responders.

13.
Ann Diagn Pathol ; 72: 152323, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38733674

ABSTRACT

High risk features in colorectal adenomatous polyps include size >1 cm and advanced histology: high-grade dysplasia and villous architecture. We investigated whether the diagnostic rates of advanced histology in colorectal adenomatous polyps were similar among institutions across the United States, and if not, could differences be explained by patient age, polyp size, and/or CRC rate. Nine academic institutions contributed data from three pathologists who had signed out at least 100 colorectal adenomatous polyps each from 2018 to 2019 taken from patients undergoing screening colonoscopy. For each case, we recorded patient age and sex, polyp size and location, concurrent CRC, and presence or absence of HGD and villous features. A total of 2700 polyps from 1886 patients (mean age: 61 years) were collected. One hundred twenty-four (5 %) of the 2700 polyps had advanced histology, including 35 (1 %) with HGD and 101 (4 %) with villous features. The diagnostic rate of advanced histology varied by institution from 1.7 % to 9.3 % (median: 4.3 %, standard deviation [SD]: 2.5 %). The rate of HGD ranged from 0 % to 3.3 % (median: 1 %, SD: 1.2 %), while the rate of villous architecture varied from 1 % to 8 % (median: 3.7 %, SD: 2.5 %). In a multivariate analysis, the factor most strongly associated with advanced histology was polyp size >1 cm with an odds ratio (OR) of 31.82 (95 % confidence interval [CI]: 20.52-50.25, p < 0.05). Inter-institutional differences in the rate of polyps >1 cm likely explain some of the diagnostic variance, but pathologic subjectivity may be another contributing factor.


Subject(s)
Adenomatous Polyps , Colorectal Neoplasms , Humans , Adenomatous Polyps/pathology , Adenomatous Polyps/epidemiology , Adenomatous Polyps/diagnosis , Middle Aged , Male , Female , Colorectal Neoplasms/pathology , Colorectal Neoplasms/epidemiology , Aged , Colonoscopy , Colonic Polyps/pathology , Colonic Polyps/diagnosis , Colonic Polyps/epidemiology , Adult , United States/epidemiology , Risk Factors
14.
BMJ Open ; 14(5): e079227, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38719307

ABSTRACT

INTRODUCTION: Person-centred care (PCC) is provision of care that is respectful of and responsive to individual patient preferences, needs and values, and ensures that patient values guide all clinical decisions. While there is a large body of evidence on the benefits of PCC in high-income countries, little research exists on PCC in Ghana and Sub-Saharan Africa at large. Most studies on PCC have focused on maternity care as part of the global movement of respectful maternity care. The few studies on patient experiences and health system responsiveness beyond maternal health also highlight gaps in patient experience and satisfaction as well as discrimination in health facilities, which leads to the most vulnerable having the poorest experiences. The protocol for this scoping review aims to systematically map the extent of literature focused on PCC in Ghana by identifying patient expectations and preferences, barriers and facilitators, and interventions. METHODS AND ANALYSIS: The protocol will be guided by the Arksey and O'Malley methodological framework and recommendations by Levac et al. A comprehensive search strategy will be used to search for published articles in PubMed, EMBASE, Web of Science and the African Journals Online from their inception to August 2022. Grey literature and reference lists of included studies will also be searched. Two independent reviewers will perform the literature search, eligibility assessments and study selection. Any disagreements will be resolved through discussion with a third reviewer. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram for the scoping reviews will be used to outline the study selection process. Extracted data from the included articles will be synthesised and reported under key concepts derived from the outcomes of the scoping review. ETHICS AND DISSEMINATION: This scoping review does not require ethical approval. The findings will be disseminated through publications and conference presentations. SCOPING REVIEW REGISTRATION: OSF Registration DOI 10.17605/OSF.IO/ZMDH9.


Subject(s)
Patient-Centered Care , Review Literature as Topic , Ghana , Databases, Bibliographic , Humans , Patient Preference
15.
Science ; 384(6695): 528-532, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38696557

ABSTRACT

Marine stratocumulus clouds are the "global reflectors," sharply contrasting with the underlying dark ocean surface and exerting a net cooling on Earth's climate. The magnitude of this cooling remains uncertain in part owing to the averaged representation of microphysical processes, such as the droplet-to-drizzle transition in global climate models (GCMs). Current GCMs parameterize cloud droplet size distributions as broad, cloud-averaged gammas. Using digital holographic measurements of discrete stratocumulus cloud volumes, we found cloud droplet size distributions to be narrower at the centimeter scale, never resembling the cloud average. These local distributions tended to form pockets of similar-looking cloud regions, each characterized by a size distribution shape that is diluted to varying degrees. These observations open the way for new modeling representations of microphysical processes.

16.
Front Immunol ; 15: 1382619, 2024.
Article in English | MEDLINE | ID: mdl-38779671

ABSTRACT

Introduction: Antibodies against the SARS-CoV-2 spike protein are a critical immune determinant for protection against the virus. While virus neutralization is a key function of spike-specific antibodies, antibodies also mediate Fc-dependent activities that can play a role in protection or pathogenesis. Methods: This study characterized serum antibody responses elicited after two doses of heterologous adenovirus-vectored (Ad26/ Ad5) vaccines. Results: Vaccine-induced antibody binding titers and Fc-mediated functions decreased over six months, while neutralization titers remained stable. Comparison of antibody isotypes elicited after Ad26/Ad5 vs. LNP-mRNA vaccination and after infection showed that anti-spike IgG1 were dominant and produced to high levels in all groups. The Ad26/Ad5 vaccines also induced IgG4 but not IgG2 and IgG3, whereas the LNP-mRNA vaccines elicited a full Ig spectrum (IgM, IgG1-4, IgA1-2). Convalescent COVID-19 patients had mainly IgM and IgA1 alongside IgG1. Despite these differences, the neutralization potencies against early variants were similar. However, both vaccine groups had antibodies with greater Fc potencies of binding complement and Fcg receptors than the COVID-19 group. The Ad26/Ad5 group also displayed a greater potency of RBD-specific antibody-mediated cellular phagocytosis. Discussion: Antibodies with distinctive quality were induced by different vaccines and infection. The data imply the utility of different vaccine platforms to elicit antibody responses with fine-tuned Fc activities.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Female , Immunoglobulin G/immunology , Immunoglobulin G/blood , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Male , Immunoglobulin Fc Fragments/immunology , Immunoglobulin Fc Fragments/genetics , Ad26COVS1/immunology , Adult , Middle Aged , Adenoviridae/immunology , Adenoviridae/genetics , Genetic Vectors , Immunoglobulin A/immunology , Immunoglobulin A/blood
17.
bioRxiv ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38798486

ABSTRACT

Post-stroke hyperglycemia occurs in 30% - 60% of ischemic stroke patients as part of the systemic stress response, but neither clinical evidence nor pre-clinical studies indicate whether post-stroke hyperglycemia affects stroke outcome. Here we investigated this issue using a mouse model of permanent ischemia. Mice were maintained either normoglycemic or hyperglycemic during the interval of 17 - 48 hours after ischemia onset. Post-stroke hyperglycemia was found to increase infarct volume, blood-brain barrier disruption, and hemorrhage formation, and to impair motor recovery. Post-stroke hyperglycemia also increased superoxide formation by peri-infarct microglia/macrophages. In contrast, post-stroke hyperglycemia did not increase superoxide formation or exacerbate motor impairment in p47 phox-/- mice, which cannot form an active superoxide-producing NADPH oxidase-2 complex. These results suggest that hyperglycemia occurring hours-to-days after ischemia can increase oxidative stress in peri-infarct tissues by fueling NADPH oxidase activity in reactive microglia/macrophages, and by this mechanism contribute to worsened functional outcome.

18.
LGBT Health ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38800875

ABSTRACT

Purpose: Tobacco use is a major health disparity for lesbian, gay, bisexual, and transgender (LGBT) populations compared with heterosexual/cisgender populations. In this scoping review, we aimed to determine if LGBT tobacco use disparities are improving or worsening over time and if trends in disparities differed across subgroups. Methods: We included articles that longitudinally explored youth and adult LGB tobacco use in the United States and Canada after searching four databases and capturing records through July 2022. Two reviewers independently screened the title/abstract and full text of 2326 and 45 articles, respectively. Eleven articles from 18 larger assessments met inclusion criteria, spanning data collection from 1996 to 2020. Results: All studies consistently demonstrated tobacco disparities for LGB populations. No articles examined longitudinal transgender tobacco disparities. Most studies focused on smoking combustible cigarettes. Disparities in heavy or daily use for all LGB youth subgroups compared with heterosexual samples appear to be shrinking longitudinally. Results for early-onset, current, and lifetime smoking were less consistent. Adult evidence was relatively sparse; however, after 2010, studies show diminishing disparities over time, except for current smoking by bisexual women. Conclusions: Large tobacco use disparities persist for LGB populations, although the size of disparities may be decreasing for some groups. Initiatives for lesbian and bisexual women and girls should be prioritized, in addition to interventions addressing LGB smoking broadly. Surveillance instruments should uniformly and consistently assess LGBT identities and tobacco use behaviors.

19.
JTCVS Open ; 18: 221-231, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38690419

ABSTRACT

Objectives: Current National Comprehensive Cancer Network guidelines recommend definitive chemoradiation rather than surgery for patients with locally advanced clinical stage T3 and N2 (stage IIIB) lung cancer involving the chest wall. The data supporting this recommendation are controversial. We studied whether surgery confers a survival advantage over definitive chemoradiation in the National Cancer Database. Methods: We identified all patients with clinical stage T3 and N2 lung cancer in the National Cancer Database from 2004 to 2017 who underwent a lobectomy with en bloc chest wall resection and compared them with patients with clinical stage T3 and N2 lung cancer who had definitive chemoradiation. We used propensity score matching to minimize confounding by indication while excluding patients with tumors in the upper lobes to exclude Pancoast tumors. We used 1:1 propensity score matching and Kaplan-Meir survival analyses to estimate associations. Results: Of 4467 patients meeting all inclusion/exclusion criteria, 210 (4.49%) had an en bloc chest wall resection. Patients undergoing surgical resection were younger (mean age = 60.3 ± 10.3 years vs 67.5 ± 10.4 years; P < .001) and had more adenocarcinoma (59.0% vs 44.5%; P < .001) but were otherwise similar in terms of sex (37.1% female vs 42.0%; P = .167) and race (Whites 84.3% vs 84.0%; P = .276) compared with the definitive chemoradiation group. After resection, there was an unadjusted 30- and 90-day mortality rate of 3.3% and 9.5%, respectively. A substantial survival benefit with surgical resection persisted after propensity score matching (log-rank P < .001). Conclusions: In this large observational study, we found that in select patients, en bloc chest wall resection for locally advanced clinical stage T3 and N2 lung cancer was associated with improved survival compared with definitive chemoradiation. National Comprehensive Cancer Network guidelines should be revisited.

20.
Am J Epidemiol ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775290

ABSTRACT

Electronic medical records (EMR) are important for rapidly compiling information to determine disease characteristics (e.g., symptoms) and risk factors (e.g., underlying comorbidities, medications) for disease-related outcomes. To assess EMR data accuracy, agreement between EMR abstractions and patient interviews was evaluated. Symptoms, medical history, and medication usage among COVID-19 patients collected from EMR and patient interviews were compared using overall agreement (same answer in EMR and interview), reported agreement (yes answer in both EMR and interview among those who reported yes in either), and Kappa statistics. Overall, patients reported more symptoms in interviews than in EMR abstractions. Overall agreement was high (≥50% for 20/23 symptoms), but only subjective fever and dyspnea had reported agreement of ≥50%. Kappa statistics for symptoms were generally low. Reported medical conditions had greater agreement with all condition categories (10/10) having ≥50% overall agreement and half (5/10) having ≥50% reported agreement. More non-prescription medications were reported in interviews than in EMR abstractions leading to low reported agreement (28%). Discordance was observed for symptoms, medical history, and medication usage between EMR abstractions and patient interviews. Investigations utilizing EMR to describe clinical characteristics and identify risk factors should consider the potential for incomplete data, particularly for symptoms and medications.

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