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1.
Spine J ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38849052

ABSTRACT

BACKGROUND CONTEXT: Isolated decompression and decompression with instrumented fusion are accepted surgical treatments for lumbar spondylolisthesis. Although isolated decompression is a less costly solution with similar patient-reported outcomes, it is associated with higher rates of re-operation than primary fusion. PURPOSE: To determine the costs associated with primary decompression, primary fusion, and decompression and fusion for degenerative spondylolisthesis. We further sought to establish at what revision rate is primary decompression still a less costly surgical treatment for degenerative lumbar spondylolisthesis. STUDY DESIGN/SETTING: A retrospective database study of the Medicare Provider Analysis and Review (MEDPAR) limited data set. PATIENT SAMPLE: Patients who underwent single-level fusion or decompression for degenerative spondylolisthesis. OUTCOME MEASURES: Cost of surgical care. METHODS: All inpatient stays that underwent surgery for single-level lumbar/lumbosacral degenerative spondylolisthesis in the 2019 calendar year (n=6,653) were queried from the MEDPAR limited data set. Patients were stratified into three cohorts: primary decompression (n=300), primary fusion (n=5,757), and revision fusion (n=566). Univariate analysis was conducted to determine cost differences between these groups and results were confirmed with multivariable regression. An economic analysis was then done to determine at what revision rate would primary decompression still be a less costly treatment choice. RESULTS: On univariate analysis, the cost of primary single-level decompression for spondylolisthesis was $14,690±9,484, the cost of primary single-level fusion was $26,376±11,967, and revision fusion was $26,686±11,309 (p<0.001). On multivariate analysis, primary fusion was associated with an increased cost of $3,751, and revision fusion was associated with increased cost of $7,502 (95%CI: 2,990-4,512, p<0.001). Economic analysis found that a revision rate less than or equal to 43.8% would still result in primary decompression being less costly for a practice than primary fusion for all patients. CONCLUSIONS: Isolated decompression for degenerative lumbar spondylolisthesis is a less costly treatment choice even with rates of revision fusion as high as 43.8%. This was true even with an assumed revision rate of 0% after primary fusion. This study solely looks at cost data, however, and many patients may still benefit from primary fusion when appropriately indicated.

2.
Sci Immunol ; 9(96): eadk8141, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848340

ABSTRACT

Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (TRMs) play an important role in site-specific immune memory, yet how LN TRMs form de novo after viral infection remains unclear. Here, we tracked the anatomical distribution of antiviral CD8+ T cells as they seeded skin and LN TRMs using a model of vaccinia virus-induced skin infection. LN TRMs localized to the draining LNs (dLNs) of infected skin, and their formation depended on the lymphatic egress of effector CD8+ T cells from the skin, already poised for residence. Effector CD8+ T cell transit through skin was required to populate LN TRMs in dLNs, a process reinforced by antigen encounter in skin. Furthermore, LN TRMs were protective against viral rechallenge in the absence of circulating memory T cells. These data suggest that a subset of tissue-infiltrating CD8+ T cells egress from tissues during viral clearance and establish a layer of regional protection in the dLN basin.


Subject(s)
Immunologic Memory , Lymph Nodes , Lymphatic Vessels , Memory T Cells , Mice, Inbred C57BL , Skin , Vaccinia virus , Animals , Lymph Nodes/immunology , Lymphatic Vessels/immunology , Skin/immunology , Memory T Cells/immunology , Mice , Immunologic Memory/immunology , Vaccinia virus/immunology , CD8-Positive T-Lymphocytes/immunology , Female , Vaccinia/immunology , Mice, Transgenic
3.
J Am Geriatr Soc ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888213

ABSTRACT

Precision medicine presents an opportunity to use novel, data-driven strategies to improve patient care. The field of precision medicine has undergone many advancements over the past few years. It has moved beyond incorporation of individualized genetic risk into medical decision-making to include multiple other factors such as unique social, demographic, behavioral, and clinical characteristics. Geriatric medicine stands to benefit heavily from the integration of precision medicine into its standard practices. Older adults, compared with other populations, have high clinical and biological heterogeneity that can alter the risks and benefits of different approaches to patient care. These factors have not been routinely considered previously by geriatricians. Yet, geriatricians' ability to address older adults' baseline heterogeneity is increasingly recognized as a cornerstone of delivering quality care in a geriatric medical practice. Given the shared focus of individualized decision-making, precision medicine is a natural fit for geriatric medicine. This manuscript provides, via cases and discussion, examples that illustrate how precision medicine can improve the care of our older patients today. We will share specific and existing tools and evidence, and review the existing multilevel barriers to further incorporate and implement these tools into clinical practice. We propose methods to address these barriers and to help realize the full potential of precision medicine for the care of older adults. We conclude with a brief discussion of potential future directions of research of precision medicine in the care of older adults.

5.
Exp Physiol ; 109(6): 992-1003, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38711207

ABSTRACT

Young individuals with post-traumatic stress disorder (PTSD) display peripheral vascular and autonomic nervous system dysfunction, two factors potentially stemming from a redox imbalance. It is currently unclear if these aforementioned factors, observed at rest, alter peripheral haemodynamic responses to exercise in this population. This study examined haemodynamic responses to handgrip exercise in young individuals with PTSD following acute antioxidant (AO) supplementation. Thirteen young individuals with PTSD (age 23 ± 3 years), and 13 age- and sex-matched controls (CTRL) participated in the study. Exercise-induced changes to arm blood flow (BF), mean arterial pressure (MAP) and vascular conductance (VC) were evaluated across two workloads of rhythmic handgrip exercise (3 and 6 kg). The PTSD group participated in two visits, consuming either a placebo (PL) or AO prior to their visits. The PTSD group demonstrated significantly lower VC (P = 0.04) across all exercise workloads (vs. CTRL), which was significantly improved following AO supplementation. In the PTSD group, AO supplementation improved VC in participants possessing the lowest VC responses to handgrip exercise, with AO supplementation significantly improving VC responses (3 and 6 kg: P < 0.01) by blunting elevated exercise-induced MAP responses (3 kg: P = 0.01; 6 kg: P < 0.01). Lower VC responses during handgrip exercise were improved following AO supplementation in young individuals with PTSD. AO supplementation was associated with a blunting of exercise-induced MAP responses in individuals with PTSD displaying elevated MAP responses. This study revealed that young individuals with PTSD exhibit abnormal, peripherally mediated exercise responses that may be linked to a redox imbalance.


Subject(s)
Antioxidants , Dietary Supplements , Exercise , Hand Strength , Stress Disorders, Post-Traumatic , Humans , Hand Strength/physiology , Antioxidants/administration & dosage , Male , Female , Young Adult , Stress Disorders, Post-Traumatic/physiopathology , Exercise/physiology , Adult , Hemodynamics/drug effects , Hemodynamics/physiology , Blood Pressure/physiology , Blood Pressure/drug effects , Regional Blood Flow/physiology , Regional Blood Flow/drug effects
6.
Sci Rep ; 14(1): 10573, 2024 05 08.
Article in English | MEDLINE | ID: mdl-38719983

ABSTRACT

Multiple sclerosis (MS) is a chronic neurological disease characterized by inflammatory demyelination that disrupts neuronal transmission resulting in neurodegeneration progressive disability. While current treatments focus on immunosuppression to limit inflammation and further myelin loss, no approved therapies effectively promote remyelination to mitigate the progressive disability associated with chronic demyelination. Lysophosphatidic acid (LPA) is a pro-inflammatory lipid that is upregulated in MS patient plasma and cerebrospinal fluid (CSF). LPA activates the LPA1 receptor, resulting in elevated CNS cytokine and chemokine levels, infiltration of immune cells, and microglial/astrocyte activation. This results in a neuroinflammatory response leading to demyelination and suppressed remyelination. A medicinal chemistry effort identified PIPE-791, an oral, brain-penetrant, LPA1 antagonist. PIPE-791 was characterized in vitro and in vivo and was found to be a potent, selective LPA1 antagonist with slow receptor off-rate kinetics. In vitro, PIPE-791 induced OPC differentiation and promoted remyelination following a demyelinating insult. PIPE-791 further mitigated the macrophage-mediated inhibition of OPC differentiation and inhibited microglial and fibroblast activation. In vivo, the compound readily crossed the blood-brain barrier and blocked LPA1 in the CNS after oral dosing. Direct dosing of PIPE-791 in vivo increased oligodendrocyte number, and in the mouse experimental autoimmune encephalomyelitis (EAE) model of MS, we observed that PIPE-791 promoted myelination, reduced neuroinflammation, and restored visual evoked potential latencies (VEP). These findings support targeting LPA1 for remyelination and encourage development of PIPE-791 for treating MS patients with advantages not seen with current immunosuppressive disease modifying therapies.


Subject(s)
Multiple Sclerosis , Receptors, Lysophosphatidic Acid , Remyelination , Animals , Multiple Sclerosis/drug therapy , Multiple Sclerosis/metabolism , Receptors, Lysophosphatidic Acid/antagonists & inhibitors , Receptors, Lysophosphatidic Acid/metabolism , Remyelination/drug effects , Humans , Mice , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism , Oligodendroglia/metabolism , Oligodendroglia/drug effects , Brain/metabolism , Brain/drug effects , Brain/pathology , Cell Differentiation/drug effects , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/metabolism , Mice, Inbred C57BL , Myelin Sheath/metabolism , Myelin Sheath/drug effects , Lysophospholipids/metabolism , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects
7.
Sci Rep ; 14(1): 11411, 2024 05 18.
Article in English | MEDLINE | ID: mdl-38762586

ABSTRACT

The high burden of anaemia during pregnancy underscores the urgent need to gain a comprehensive understanding of the factors contributing to its widespread occurrence. Our study assessed the prevalence and the trends of moderate-to-severe anaemia (MSA) in late pregnancy (28 to 36 weeks) and then investigated the key determinants driving this prevalence among women in Lagos, Nigeria. We conducted a secondary data analysis involving 1216 women enrolled in the Predict-PPH study between January and March 2023. We employed a multivariate binary logistic regression model with a backward stepwise selection approach to identify significant predictors of MSA. The study revealed a 14.5% prevalence of MSA during pregnancy. Independent predictors of MSA included having given birth to two or more children (adjusted odds ratio = 1.46, 95% confidence interval: 1.03-2.07), having a maternal body mass index (BMI) of 28 kg/m2 or higher (adjusted odds ratio = 1.84, 95% confidence interval: 1.29-2.61), having less than tertiary education (adjusted odds ratio = 1.51, 95% confidence interval: 1.08-2.11), and being unemployed (adjusted odds ratio = 1.97, 95% confidence interval: 1.19-3.26). It is crucial for pregnant women, particularly those with higher parities and elevated BMI, to be monitored regularly for anaemia and its consequences during their antenatal care. Additionally, addressing the link between low education, unemployment, and anaemia necessitates comprehensive strategies that empower women in terms of education and economic status to enhance the overall well-being of individuals and communities, ultimately reducing the prevalence of anaemia and associated health issues in pregnancy.


Subject(s)
Anemia , Pregnancy Complications, Hematologic , Pregnancy Trimester, Third , Humans , Female , Pregnancy , Nigeria/epidemiology , Anemia/epidemiology , Adult , Prevalence , Cross-Sectional Studies , Pregnancy Complications, Hematologic/epidemiology , Young Adult , Risk Factors , Body Mass Index
8.
Elife ; 122024 Apr 05.
Article in English | MEDLINE | ID: mdl-38578680

ABSTRACT

Heterogeneity in endothelial cell (EC) sub-phenotypes is becoming increasingly appreciated in atherosclerosis progression. Still, studies quantifying EC heterogeneity across whole transcriptomes and epigenomes in both in vitro and in vivo models are lacking. Multiomic profiling concurrently measuring transcriptomes and accessible chromatin in the same single cells was performed on six distinct primary cultures of human aortic ECs (HAECs) exposed to activating environments characteristic of the atherosclerotic microenvironment in vitro. Meta-analysis of single-cell transcriptomes across 17 human ex vivo arterial specimens was performed and two computational approaches quantitatively evaluated the similarity in molecular profiles between heterogeneous in vitro and ex vivo cell profiles. HAEC cultures were reproducibly populated by four major clusters with distinct pathway enrichment profiles and modest heterogeneous responses: EC1-angiogenic, EC2-proliferative, EC3-activated/mesenchymal-like, and EC4-mesenchymal. Quantitative comparisons between in vitro and ex vivo transcriptomes confirmed EC1 and EC2 as most canonically EC-like, and EC4 as most mesenchymal with minimal effects elicited by siERG and IL1B. Lastly, accessible chromatin regions unique to EC2 and EC4 were most enriched for coronary artery disease (CAD)-associated single-nucleotide polymorphisms from Genome Wide Association Studies (GWAS), suggesting that these cell phenotypes harbor CAD-modulating mechanisms. Primary EC cultures contain markedly heterogeneous cell subtypes defined by their molecular profiles. Surprisingly, the perturbations used here only modestly shifted cells between subpopulations, suggesting relatively stable molecular phenotypes in culture. Identifying consistently heterogeneous EC subpopulations between in vitro and ex vivo models should pave the way for improving in vitro systems while enabling the mechanisms governing heterogeneous cell state decisions.


Subject(s)
Atherosclerosis , Coronary Artery Disease , Humans , Atherosclerosis/metabolism , Chromatin/metabolism , Coronary Artery Disease/genetics , Endothelial Cells/metabolism , Genome-Wide Association Study
9.
BMC Public Health ; 24(1): 1028, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609913

ABSTRACT

BACKGROUND: Most previous clinical studies investigating the connection between prenatal anaemia and postpartum haemorrhage (PPH) have reported conflicting results. OBJECTIVES: We examined the association between maternal prenatal anaemia and the risk of PPH in a large cohort of healthy pregnant women in five health institutions in Lagos, Southwest Nigeria. METHODS: This was a prospective cohort analysis of data from the Predict-PPH study that was conducted between January and June 2023. The study enrolled n = 1222 healthy pregnant women giving birth in five hospitals in Lagos, Nigeria. The study outcome, WHO-defined PPH, is postpartum blood loss of at least 500 milliliters. We used a multivariable logistic regression model with a backward stepwise conditional approach to examine the association between prenatal anaemia of increasing severity and PPH while adjusting for confounding factors. RESULTS: Of the 1222 women recruited to the Predict-PPH study between January and June 2023, 1189 (97·3%) had complete outcome data. Up to 570 (46.6%) of the enrolled women had prenatal anaemia while 442 (37.2%) of those with complete follow-up data had WHO-defined PPH. After controlling for potential confounding factors, maternal prenatal anaemia was independently associated with PPH (adjusted odds ratio = 1.37, 95% confidence interval: 1.05-1.79). However, on the elimination of interaction effects of coexisting uterine fibroids and mode of delivery on this association, a sensitivity analysis yielded a lack of significant association between prenatal anaemia and PPH (adjusted odds ratio = 1.27, 95% confidence interval: 0.99-1.64). We also recorded no statistically significant difference in the median postpartum blood loss in women across the different categories of anaemia (P = 0.131). CONCLUSION: Our study revealed that prenatal anaemia was not significantly associated with PPH. These findings challenge the previously held belief of a suspected link between maternal anaemia and PPH. This unique evidence contrary to most previous studies suggests that other factors beyond prenatal anaemia may contribute more significantly to the occurrence of PPH. This highlights the importance of comprehensive assessment and consideration of various maternal health factors in predicting and preventing this life-threatening obstetric complication.


Subject(s)
Anemia , Postpartum Hemorrhage , Pregnancy , Humans , Female , Nigeria/epidemiology , Postpartum Hemorrhage/epidemiology , Prospective Studies , Anemia/epidemiology , Family , Vitamins
10.
Org Lett ; 26(16): 3355-3360, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38604973

ABSTRACT

A two-step protocol for the conversion of alkyl-substituted alkynes to 1,3-enynes is reported. In this α-methenylation process, an iron-catalyzed propargylic C-H functionalization delivers tetramethylpiperidine-derived homopropargylic amines which undergo facile Cope elimination upon N-oxidation to afford the enyne products. A range of aryl alkyl and dialkyl acetylenes were found to be suitable substrates for this process, which constitutes an alkyne analogue for the Eschenmoser methenylation of carbonyl derivatives. In addition, a new bench-stable precatalyst for iron-catalyzed propargylic C-H functionalization is reported.

11.
Sci Adv ; 10(14): eadj9305, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38569042

ABSTRACT

The power and scope of disease modeling can be markedly enhanced through the incorporation of broad genetic diversity. The introduction of pathogenic mutations into a single inbred mouse strain sometimes fails to mimic human disease. We describe a cross-species precision disease modeling platform that exploits mouse genetic diversity to bridge cell-based modeling with whole organism analysis. We developed a universal protocol that permitted robust and reproducible neural differentiation of genetically diverse human and mouse pluripotent stem cell lines and then carried out a proof-of-concept study of the neurodevelopmental gene DYRK1A. Results in vitro reliably predicted the effects of genetic background on Dyrk1a loss-of-function phenotypes in vivo. Transcriptomic comparison of responsive and unresponsive strains identified molecular pathways conferring sensitivity or resilience to Dyrk1a1A loss and highlighted differential messenger RNA isoform usage as an important determinant of response. This cross-species strategy provides a powerful tool in the functional analysis of candidate disease variants identified through human genetic studies.


Subject(s)
Pluripotent Stem Cells , Animals , Mice , Humans , Phenotype
12.
Surg Open Sci ; 19: 24-27, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38585040

ABSTRACT

The treatment of diverticulitis is experiencing a shift in management due to a number of large scale clinical trials. For instance, clinicians are beginning to recognize that avoidance of antibiotics in uncomplicated diverticulitis is not associated with worse outcomes. Additionally, while the decision to proceed with elective surgical resection for recurrent uncomplicated disease is less conclusive and favors a patient-centric approach, complicated disease with a large abscess denotes more aggressive disease and would likely benefit from elective surgical resection. Lastly, in patient with acutely perforated diverticulitis who require urgent surgical intervention, laparoscopic lavage is generally not recommended due to high re-intervention rates and the preferred surgical procedure is primary anastomosis with or without diversion due to high morbidity and low rates of Hartmann reversal.

13.
Spine J ; 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38499062

ABSTRACT

BACKGROUND CONTEXT: Left-digit bias is a behavioral heuristic or cognitive "shortcut" in which the leftmost digit of a number, such as patient age, disproportionately influences surgical decisions. PURPOSE: To determine if left-digit bias in patient age influences the decision to perform arthrodesis with instrumentation vs decompression in lumbar spinal stenosis (LSS). DESIGN: Retrospective cohort. PATIENT SAMPLE: Patients with an ICD-10 diagnosis of lumbar stenosis or spondylolisthesis identified in the 2017-2021 National Surgical Quality Improvement Program (NSQIP) database. OUTCOME MEASURES: The primary outcome was the percent of patients who underwent arthrodesis with instrumentation (AwI). Matched age group comparisons without left-digit differences (ie, 76/77 vs 78/79, 80/81 vs 82/83, etc.) were performed to isolate the effect of the heuristic. Secondary outcomes including peri-operative events and complications were also compared within AwI and decompression cohorts. METHODS: Using CPT codes, procedures were classified as either AwI or decompression. Patients were grouped into 6 cohorts based on 2-year age windows (74/75, 76/77, 78/79, 80/81, 82/83, 84/85). The cohorts were propensity matched with neighboring age groups based on the presence of spondylolisthesis, demographics, and comorbidities. The primary comparison was between those aged 78/79 vs 80/81. RESULTS: After matching, the primary cohort consisted of two groups of 1,550 patients (aged 78/79 and 80/81). Patients aged 80/81 were less likely to undergo AwI than patients aged 78/79 (23.5% vs 27.2%, p=.021). AwI procedures occurred at similar rates between age groups with the same left digit. Within the decompression and AwI cohorts, there were no differences in secondary outcomes between patients aged 78/79 and 80/81. CONCLUSIONS: LSS patients aged 80/81 are less likely to undergo AwI than patients aged 78/79, regardless of comorbidities. This was not seen when comparing patients with similar left digits in age. Until objective measures of physiologic capacity are established, left-digit bias may influence clinical decisions.

14.
Evol Appl ; 17(3): e13650, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38524684

ABSTRACT

Plant collections held by botanic gardens and arboreta are key components of ex situ conservation. Maintaining genetic diversity in such collections allows them to be used as resources for supplementing wild populations. However, most recommended minimum sample sizes for sufficient ex situ genetic diversity are based on microsatellite markers, and it remains unknown whether these sample sizes remain valid in light of more recently developed next-generation sequencing (NGS) approaches. To address this knowledge gap, we examine how ex situ conservation status and sampling recommendations differ when derived from microsatellites and single nucleotide polymorphisms (SNPs) in garden and wild samples of two threatened oak species. For Quercus acerifolia, SNPs show lower ex situ representation of wild allelic diversity and slightly lower minimum sample size estimates than microsatellites, while results for each marker are largely similar for Q. boyntonii. The application of missing data filters tends to lead to higher ex situ representation, while the impact of different SNP calling approaches is dependent on the species being analyzed. Measures of population differentiation within species are broadly similar between markers, but larger numbers of SNP loci allow for greater resolution of population structure and clearer assignment of ex situ individuals to wild source populations. Our results offer guidance for future ex situ conservation assessments utilizing SNP data, such as the application of missing data filters and the usage of a reference genome, and illustrate that both microsatellites and SNPs remain viable options for botanic gardens and arboreta seeking to ensure the genetic diversity of their collections.

15.
J Adolesc Health ; 74(5): 1053-1056, 2024 May.
Article in English | MEDLINE | ID: mdl-38416101

ABSTRACT

PURPOSE: We describe trends in psilocybin exposures among adolescents and young adults as reported to US poison centers over the past decade. METHODS: We queried the National Poison Data System for cases involving psilocybin during January 1, 2013-December 31, 2022. Persons aged 13-25 years were included. We examined exposures to psilocybin by demographics, clinical effects, level of care, and medical outcome. RESULTS: During the 10-year study period, 4,055 psilocybin-involved exposures were reported among adolescents and young adults, 2,667 (65.8%) being single substance exposures. Most single substance cases received medical attention (adolescents: 75.3% [n = 1,176], young adults: 72.1% [n = 797]). We did not find significant change in the number of cases during 2013-2018. Cases started increasing in 2019. In 2022, cases more than tripled among adolescents and more than doubled among young adults, compared to 2018 (p < .0001). DISCUSSION: Continued national surveillance is critical to determine the impact of psilocybin exposures on youth as it becomes increasingly available.


Subject(s)
Poisons , Psilocybin , Adolescent , Young Adult , Humans , United States/epidemiology , Poison Control Centers , Databases, Factual
16.
Am J Dermatopathol ; 46(3): 137-146, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38354382

ABSTRACT

ABSTRACT: Most melanocytic tumors are classified as benign or malignant based on clinical morphology, histology, and immunohistochemical (IHC) analysis. A subset of more challenging cases with ambiguous features may require further evaluation with established ancillary diagnostic molecular studies, including fluorescence in situ hybridization and/or single nucleotide polymorphism array, to increase diagnostic certainty. More recently, a diagnostic gene expression-profiling (GEP) assay and an IHC stain for the detection of PRAME (PReferentially expressed Antigen in MElanoma) have been developed. The use of PRAME IHC has been validated in cases of unequivocal and ambiguous melanocytic proliferations via comparing results with fluorescence in situ hybridization and/or single nucleotide polymorphism array. A study comparing performance metrics of PRAME IHC and diagnostic GEP has not been previously published. Herein, we evaluated the use of PRAME IHC in 55 melanocytic tumors with challenging histomorphology by comparing the results with diagnostic GEP and final histomorphologic diagnosis. Intertest agreement occurred in 88% of cases. PRAME IHC supported the final diagnosis in 89% of cases with a sensitivity of 79%, specificity of 95%, and positive predictive value of 88.2%. GEP agreed with the final diagnosis in 88% of cases with a sensitivity of 65%, 97% specificity, and positively predicted melanoma in 91.7% of cases. Because the results of this study align with past publications evaluating the performance metrics of PRAME IHC, showing it to be as sensitive as and more cost effective than all other ancillary molecular tests, we propose the use of PRAME IHC as the optimal first-line diagnostic tool for ambiguous melanocytic proliferations.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/diagnosis , Melanoma/genetics , Melanoma/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Skin Neoplasms/pathology , In Situ Hybridization, Fluorescence , Immunohistochemistry , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Gene Expression , Antigens, Neoplasm/genetics
17.
Int J Gynaecol Obstet ; 166(1): 343-352, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38234155

ABSTRACT

OBJECTIVES: There is currently a limited ability to accurately identify women at risk of postpartum hemorrhage (PPH). We conducted the "Predict-PPH" study to develop and evaluate an antepartum prediction model and its derived risk-scoring system. METHODS: This was a prospective cohort study of healthy pregnant women who registered and gave birth in five hospitals in Lagos, Nigeria, from January to June 2023. Maternal antepartum characteristics were compared between women with and without PPH. A predictive multivariable model was estimated using binary logistic regression with a backward stepwise approach eliminating variables when P was greater than 0.10. Statistically significant associations in the final model were reported when P was less than 0.05. RESULTS: The prevalence of PPH in the enrolled cohort was 37.1%. Independent predictors of PPH such as maternal obesity (adjusted odds ratio [aOR] 3.25, 95% confidence interval [CI] 2.47-4.26), maternal anemia (aOR 1.32, 95% CI 1.02-1.72), previous history of cesarean delivery (aOR 4.24, 95% CI 3.13-5.73), and previous PPH (aOR 2.65, 95% CI 1.07-6.56) were incorporated to develop a risk-scoring system. The area under the receiver operating characteristic curve (AUROC) for the prediction model and risk scoring system was 0.72 (95% CI 0.69-0.75). CONCLUSION: We recorded a relatively high prevalence of PPH. Our model performance was satisfactory in identifying women at risk of PPH. Therefore, the derived risk-scoring system could be a useful tool to screen and identify pregnant women at risk of PPH during their routine antenatal assessment for birth preparedness and complication readiness.


Subject(s)
Postpartum Hemorrhage , Humans , Female , Postpartum Hemorrhage/epidemiology , Nigeria/epidemiology , Pregnancy , Prospective Studies , Adult , Risk Assessment , Risk Factors , Prevalence , Young Adult , Logistic Models , ROC Curve , Cohort Studies
18.
J Orthop Trauma ; 38(5): 247-253, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38259060

ABSTRACT

OBJECTIVES: To assess the relationship between patient smoking status and fracture-related infection (FRI) characteristics including patient symptoms at FRI presentation, bacterial species of FRI, and rates of fracture union. DESIGN: Retrospective cohort study. SETTING: Urban level 1 trauma center. PATIENT SELECTION CRITERIA: All patients undergoing reoperation for FRI from January 2013 to April 2021 were identified through manual review of an institutional database. OUTCOME MEASURES AND COMPARISONS: Data including patient demographics, fracture characteristics, infection presentation, and hospital course were collected through review of the electronic medical record. Patients were grouped based on current smoker versus nonsmoker status. Hospital course and postoperative outcomes of these groups were then compared. Risk factors of methicillin-resistant Staphylococcus aureus (MRSA) infection, Staphylococcus epidermidis infection, and sinus tract development were evaluated using multivariable logistic regression. RESULTS: A total of 301 patients, comprising 155 smokers (51%) and 146 nonsmokers (49%), undergoing FRI reoperation were included. Compared with nonsmokers, smokers were more likely male (69% vs. 56%, P = 0.024), were younger at the time of FRI reoperation (41.7 vs. 49.5 years, P < 0.001), and had lower mean body mass index (27.2 vs. 32.0, P < 0.001). Smokers also had lower prevalence of diabetes mellitus (13% vs. 25%, P = 0.008) and had higher Charlson Comorbidity Index 10-year estimated survival (93% vs. 81%, P < 0.001). Smokers had a lower proportion of S. epidermidis infections (11% vs. 20%, P = 0.037), higher risk of nonunion after index fracture surgery (74% vs. 61%, P = 0.018), and higher risk of sinus tracts at FRI presentation (38% vs. 23%, P = 0.004). On multivariable analysis, smoking was not found to be associated with increased odds of MRSA infection. CONCLUSIONS: Among patients who develop a FRI, smokers seemed to have better baseline health regarding age, body mass index, diabetes mellitus, and Charlson Comorbidity Index 10-year estimated survival compared with nonsmokers. Smoking status was not significantly associated with odds of MRSA infection. However, smoking status was associated with increased risk of sinus tract development and nonunion and lower rates of S. epidermidis infection at the time of FRI reoperation. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Diabetes Mellitus , Fractures, Bone , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Male , Retrospective Studies , Smoking/adverse effects , Staphylococcal Infections/microbiology , Hospitals
19.
Arch Sex Behav ; 53(3): 1197-1211, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38212437

ABSTRACT

Latinx gay, bisexual, and other men who have sex with men (LMSM) report lower pre-exposure prophylaxis (PrEP) use than their white, non-Latinx counterparts. We hypothesize that this disparity is partially attributable to social ecological factors that can be addressed via prevention interventions. In this retrospective study, we first examined data from 253 LMSM to determine whether theorized associations existed between acquisition of a PrEP prescription (uptake) in relation to several social ecological factors based on a conceptual framework of determinants of access to and uptake of PrEP for LMSM. We also explored relations between frequency of PrEP use (adherence) and social ecological factors with a subsample of 33 LMSM who had initiated PrEP 12 months prior to assessment. In this study, individual-level factors from this framework included age and socioeconomic status. Perceived access to medical care represented both individual- and community-level determinants of PrEP uptake and adherence. Interpersonal-level factors were social support and relationship status. Structural/cultural-level factors were sexual identity development status, the masculinity norm of heterosexual self-presentation, traditional Latinx masculine gender role beliefs of machismo and caballerismo, racial identity, and immigration status. Results indicated that older men and those who endorsed the synthesis/integration status of sexual identity development were more likely to acquire a PrEP prescription during their lifetime in comparison to peers. PrEP adherence was linked with being older, reporting higher socioeconomic status, reporting more appraisal social support, self-identifying as white-Latinx, being U.S.-born, and endorsing less sexual identity uncertainty and more heterosexual self-presentation. Results specify modifiable factors that may inform tailored, community-based prevention efforts to increase PrEP use and decrease existing HIV/AIDS disparities among LMSM.


Subject(s)
HIV Infections , Sexual and Gender Minorities , Humans , Male , Hispanic or Latino , HIV Infections/prevention & control , Homosexuality, Male , Retrospective Studies , White
20.
Quant Imaging Med Surg ; 14(1): 1086-1107, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38223128

ABSTRACT

Background and Objective: Diffusion tensor imaging (DTI) has been implemented in a breadth of scientific investigations of optic neuropathies, though it has yet to be fully adopted for diagnosis or prognosis. This is potentially due to a lack of standardization and weak replication of results. The aim of this investigation was to review DTI results from studies specific to three distinct optic neuropathies in order to probe its current clinical utility. Methods: We reviewed the DTI literature specific to primary open-angle glaucoma (POAG), optic neuritis (ON), and traumatic optic neuropathy (TON) by systematically searching the PubMed database on March 1st, 2023. Four distinct DTI metrics are considered: fractional anisotropy (FA), along with mean diffusivity (MD, axial diffusivity (AD), and radial diffusivity (RD). Results from within-group, between-group, and correlational studies were thoroughly assessed. Key Content and Findings: POAG studies most consistently report a decrease in FA, especially in the optic radiations, followed in prevalence by an increase in RD and then MD, whilst AD yields conflicting results between studies. It is notable that there is not an equal distribution of investigated DTI metrics, with FA utilized the most, followed by MD, RD, and AD. Studies of ON are similar in that the most consistent findings are specific to FA, RD, and MD. These results are specific to the optic nerve and radiation since only one study measured the intermediary regions. More studies are needed to assess the effect that ON has on the tracts of the visual system. Finally, only three studies assessing DTI of TON have been performed to date, displaying low to moderate replicability of results. To improve the level of agreement between studies assessing each optic neuropathy, an increased level of standardization is recommended. Conclusions: Both POAG and ON studies have yielded some prevalent DTI findings, both for contrast and correlation-based assessments. Although the clinical need is high for TON, considering the limitations of the current diagnostic tools, too few studies exist to make confident conclusions. Future use of standardized and longitudinal DTI, along with the foreseen methodological and technical improvements, is warranted to effectively study optic neuropathies.

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