Publications by authors named "Sijin Wen"

179 Publications

Nuclear Aurora-A kinase-induced hypoxia signaling drives early dissemination and metastasis in breast cancer: implications for detection of metastatic tumors.

Oncogene 2021 Jul 29. Epub 2021 Jul 29.

Department of Biochemistry, West Virginia University, Morgantown, WV, USA.

Metastatic breast cancer causes most breast cancer-associated deaths, especially in triple negative breast cancers (TNBC). The metastatic drivers of TNBCs are still poorly understood, and effective treatment non-existent. Here we reveal that the presence of Aurora-A Kinase (AURKA) in the nucleus and metastatic dissemination are molecularly connected through HIF1 (Hypoxia-Inducible Factor-1) signaling. Nuclear AURKA activates transcription of "hypoxia-induced genes" under normoxic conditions (pseudohypoxia) and without upregulation of oxygen-sensitive HIF1A subunit. We uncover that AURKA preferentially binds to HIF1B and co-localizes with the HIF complex on DNA. The mass-spectrometry analysis of the AURKA complex further confirmed the presence of CBP and p300 along with other TFIIB/RNApol II components. Importantly, the expression of multiple HIF-dependent genes induced by nuclear AURKA (N-AURKA), including migration/invasion, survival/death, and stemness, promote early cancer dissemination. These results indicate that nuclear, but not cytoplasmic, AURKA is a novel driver of early metastasis. Analysis of clinical tumor specimens revealed a correlation between N-AURKA presence and decreased patient survival. Our results establish a mechanistic link between two critical pathways in cancer metastasis, identifying nuclear AURKA as a crucial upstream regulator of the HIF1 transcription complex and a target for anti-metastatic therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-021-01969-1DOI Listing
July 2021

Outcomes of Idiopathic Pulmonary Fibrosis Improve with Obesity: A Rural Appalachian Experience.

South Med J 2021 Jul;114(7):424-431

From the Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Section of Internal Medicine, the Department of Radiology, and the Department of Biostatistics, School of Public Health, West Virginia University, Morgantown, and the US Environmental Protection Agency, Chapel Hill, North Carolina.

Objectives: Obesity can be an independent predictor of fibrosis in tissues, including the liver, heart, and skin. We evaluated a rural Appalachian cohort of idiopathic pulmonary fibrosis (IPF) for its relation to obesity.

Methods: Using American Thoracic Society 2018 diagnostic guidelines, an IPF cohort was systematically identified at an Appalachian academic medical center (2015-2019). The cohort was categorized in subgroups of body mass index (BMI) <30 or BMI ≥30 kg/m. Demographics, clinical variables, and treatment details were collected retrospectively and evaluated for their associations with obesity.

Results: In our IPF cohort (N = 138), a usual interstitial pneumonia pattern was less prevalent in the obese group (n = 49) relative to the nonobese group (69% vs 85%, respectively). The obese group was younger (mean age 73.27 ± 9.12 vs 77.97 ± 9.59 years) and had a higher prevalence of hypertension (90% vs 72%), hyperlipidemia (83% vs 68%), diabetes mellitus (47% vs 25%), sleep-disordered breathing (47% vs 25%), chronic pain disorders (28% vs 15%), and deep vein thrombosis (19% vs 7%). An increased proportion of obese-IPF patients was seen at a tertiary or an interstitial lung disease center, with more surgical lung biopsies performed and incident diagnosis (ie, within 6 months of presentation) assigned. Only a minority of patients underwent lung transplantation (3.6%), all of them from the obese-IPF subgroup. Approximately 30% of the total IPF cohort died, with a lower mortality observed in the obese group (35% vs 20%, 0.017). An increasing BMI predicted a better survival in the total IPF cohort (BMI 25-29.9, 20-24.9, and <20 had mortality rates of 20%, 47%, and 75%, respectively; 0.001).

Conclusions: Our study represents a first known effort to develop an IPF cohort in a rural Appalachian region. Although they shared an increased burden of comorbidities, the obese subgroup showed less advanced fibrosis with a lower mortality rate relative to nonobese subgroup, suggesting a potential "obesity paradox" in IPF. The study findings significantly advance our understanding of challenges posed by IPF in a rural population that also suffers from an alarming rate of obesity. We highlight the need for the multidisciplinary management of these patients and prospective studies to better define this complex relation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14423/SMJ.0000000000001275DOI Listing
July 2021

The Effect of Lumpectomy and Cavity Shave Margin Status on Recurrence and Survival in Breast-Conserving Surgery.

Am Surg 2021 Jul 1:31348211030464. Epub 2021 Jul 1.

Department of Surgery, 5631West Virginia University, Morgantown, WV, USA.

Background/objective: Cavity shave margins (CSMs) decrease rate of positive margins and need for re-excision. Recurrence data following breast-conserving surgery (BCS) are not always available in large cancer registries. We sought to define our recurrence and survival data in BCS with routine excision of CSMs.

Methods: A single institution, 10-year retrospective review of breast cancer patients who underwent BCS with routine CSMs was conducted. Cavity shave margin technique was standard. Cox proportional hazard analyses and the Kaplan-Meier method were used to estimate recurrence and survival.

Results: Breast-conserving surgery with CSM was performed in 839 patients. Re-excision rate to achieve negative margins was 8.5%. Fifty-two patients (75%) underwent margin re-excision vs 18 patients (25%) underwent salvage mastectomy. Positive margin rate stratified by tumor histology was highest for invasive lobular carcinoma followed by mixed invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS), followed by pure DCIS and lowest for IDC. Length of follow-up was (4.7 ± 2.6, years). Overall recurrence rate (locoregional and systemic) was 4.3%: highest in patients with negative lumpectomy margin but positive CSM (L-S+ = 15%) followed by positive lumpectomy and CSMs (L+S+ = 14%), followed by patients with positive lumpectomy margin but negative CSMs (L+S- = 13%) and lowest for negative lumpectomy and CSM (L-S- = 5%), ( = .0008). There was no difference in 5-year breast cancer-specific survival between the 4 subgroups: 96% for L-S-, 86.7% L-S+, 94.7% L+S+ and 90% L+S- ( = .094).

Conclusions: Recurrence following BCS with CSMs can be stratified based on both lumpectomy and cavity shave margin positivity. Routine excision of CSMs allows identification of these patient subsets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/00031348211030464DOI Listing
July 2021

Verifying intervention fidelity procedures for a palliative home care intervention with pilot study results.

Res Nurs Health 2021 Jun 30. Epub 2021 Jun 30.

School of Nursing, University of Kansas Medical Center, Kansas City, Kansas, USA.

Fidelity (consistency of intervention implementation) is essential to rigorous research. Intervention fidelity maintains study internal validity, intervention reproducibility, and transparency in the research conduct. The purpose of this manuscript is to describe intervention fidelity strategies/procedures developed for a pilot study testing a new palliative care nursing intervention (FamPALcare) for families managing advanced lung disease. The procedures described herein are based on the fidelity best practices recommendations from the NIH Consortium. An evidence-based checklist guided observational ratings of the fidelity procedures used and the intervention content implemented in each intervention session. Descriptive data on how participants understood (received), enacted, or used the intervention information were summarized. The fidelity checklist observational scores found ≥93% of the planned intervention content was implemented, and the fidelity strategies were adhered to consistently during each intervention session. The small variation (7%) in implementation was expected and related to participants' varying experiences, input, and/or questions. The helpfulness scale items include participants' ability to use home care resources, to anticipate and manage end-of-life symptoms, and to use Advance Directive forms. The high ratings (M = 4.4) on the 1-5 (very helpful) Likert Helpfulness Scale verified participants utilized the information from the intervention. Furthermore, there was an improvement in patients' breathlessness scores and completion of Advance Directive forms at 3 months after baseline. It is essential to plan intervention fidelity strategies to use throughout a study and to report fidelity results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nur.22166DOI Listing
June 2021

Toxicity assessment of concurrent gabapentin/pregabalin administration with high-dose melphalan in autologous hematopoietic cell transplant recipients.

Support Care Cancer 2021 Jun 30. Epub 2021 Jun 30.

Department of Pharmacy, West Virginia University Medicine, 1 Medical Center Drive, Morgantown, WV, 26506, USA.

A theoretical pharmacokinetic interaction mediated through L-amino acid transporter 1 and 2 exists between gabapentin (GP) and pregabalin (PG) with melphalan. Peripheral neuropathy is a common toxicity of various multiple myeloma regimens commonly utilized prior to autologous hematopoietic cell transplant (auto-HCT) with high-dose melphalan (HD-Mel). Therefore, it is likely concurrent administration of either GP or PG will occur in patients receiving HD-Mel conditioning for auto-HCT, which could potentially increase cellular uptake and worsen the mucosal injury. A retrospective chart review of adult patients from January 2012 to July 2016 who received HD-Mel (140-200 mg/m) at West Virginia University Medicine was performed to assess toxicity and outcomes in these patients. A total of 80 patients were included in the study, with 30 patients receiving GP or PG and 50 control patients. There were no significant differences in grade 2 or higher mucositis, admissions for nausea/vomiting/diarrhea, intravenous opioid requirements, oral topical therapies, antidiarrheal medication use, rescue anti-emetics, days of nausea or vomiting, pain scores, neutrophil or platelet engraftment, treatment-related mortality, progression-free survival, or overall survival. Our data suggest that it is safe to continue GP/PG therapy throughout HD-Mel therapy, with no negative transplant outcomes. Prospective studies or evaluations of larger databases are necessary to better characterize the clinical effect of concomitant therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-021-06385-5DOI Listing
June 2021

Formulation and In Vitro Characterization of PLGA/PLGA-PEG Nanoparticles Loaded with Murine Granulocyte-Macrophage Colony-Stimulating Factor.

AAPS PharmSciTech 2021 Jun 24;22(5):191. Epub 2021 Jun 24.

Department of Microbiology, Immunology, and Cell Biology, West Virginia University, PO Box 9177, Morgantown, West Virginia, 26506-9177, USA.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has demonstrated notable clinical activity in cancer immunotherapy, but it is limited by systemic toxicities, poor bioavailability, rapid clearance, and instability in vivo. Nanoparticles (NPs) may overcome these limitations and provide a mechanism for passive targeting of tumors. This study aimed to develop GM-CSF-loaded PLGA/PLGA-PEG NPs and evaluate them in vitro as a potential candidate for in vivo administration. NPs were created by a phase-separation technique that did not require toxic/protein-denaturing solvents or harsh agitation techniques and encapsulated GM-CSF in a more stable precipitated form. NP sizes were within 200 nm for enhanced permeability and retention (EPR) effect with negative zeta potentials, spherical morphology, and high entrapment efficiencies. The optimal formulation was identified by sustained release of approximately 70% of loaded GM-CSF over 24 h, alongside an average size of 143 ± 35 nm and entrapment efficiency of 84 ± 5%. These NPs were successfully freeze-dried in 5% (w/v) hydroxypropyl-β-cyclodextrin for long-term storage and further characterized. Bioactivity of released GM-CSF was determined by observing GM-CSF receptor activation on murine monocytes and remained fully intact. NPs were not cytotoxic to murine bone marrow-derived macrophages (BMDMs) at concentrations up to 1 mg/mL as determined by MTT and trypan blue exclusion assays. Lastly, NP components generated no significant transcription of inflammation-regulating genes from BMDMs compared to IFNγ+LPS "M1" controls. This report lays the preliminary groundwork to validate in vivo studies with GM-CSF-loaded PLGA/PEG-PLGA NPs for tumor immunomodulation. Overall, these data suggest that in vivo delivery will be well tolerated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1208/s12249-021-02049-zDOI Listing
June 2021

Impact of anti-anaerobic antibiotic activity on graft-versus-host disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients at an institution that utilizes antibiotic cycling.

Transpl Infect Dis 2021 Jun 24:e13676. Epub 2021 Jun 24.

Department of Pharmacy, West Virginia University Hospital, Morgantown, WV, USA.

Background: At our institution, antibiotic cycling for febrile neutropenia is utilized to increase heterogeneity of antibiotic exposure in patients who have undergone an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Development of acute graft-versus-host disease (aGVHD) has been associated with low diversity within stool microbiota. To date, discordant outcomes have been reported implicating anti-anaerobic antibiotic use with the development of aGVHD, and there is currently a lack of published data available in an antibiotic cycled environment. The objective of this study was to determine if there is a difference in the rate of aGVHD in patients who receive anti-anaerobic cycled antibiotics compared with other cycled antibiotics.

Methods: This was a retrospective, observational study evaluating rates of aGVHD in patients who received antibiotics with anaerobic vs non-anaerobic coverage post-allo-HSCT from January 2008 to January 2018. Univariate and multivariable analyses were performed to assess associations with aGVHD. Secondary outcomes include rate of all stages of aGVHD, progression-free survival, overall survival, 100-day treatment-related mortality (TRM), and 1-year TRM.

Results: A total of 273 patients were included in the study. Baseline characteristics were similar between groups, except patients who received anti-anaerobic antibiotics had more unrelated donors (P = .002), were more likely to get myeloablative preparatory regimens (P = .009), had less subtherapeutic calcineurin inhibitor serum concentrations (P = .001), and more often received T-cell depletion (P = .004). The incidence of grades II-IV aGVHD post-HSCT in patients who received anti-anaerobic antibiotics was 32.6% compared with 18.8% in patients who received other antibiotics (P = .015). Multivariable analysis showed that the occurrence of grades II-IV aGVHD was associated with cytomegalovirus reactivation (OR = 2.1, 95% CI = 1.0-4.5, P = .047), unrelated donors (OR = 6.1, 95% CI = 2.3-16.6, P < .001), and use of anti-anaerobic antibiotics (OR = 2.3, 95% CI = 1.1-4.8, P = .021). A 100-day TRM in patients who received anti-anaerobic antibiotics was 9.6% compared with 3.6% in patients who received other antibiotics (P = .046). One-year TRM in patients who received anti-anaerobic antibiotics was 25.2% compared with 13.8% in patients who received other antibiotics (P = .017). There was no statistically significant difference seen between groups in progression free survival or overall survival.

Conclusion: Variability in baseline characteristics limits ability to make strong conclusions, but patients who received antibiotics with anaerobic coverage during the first 30 days after an allogeneic HSCT appeared to be at an increased risk of developing aGVHD and TRM. Larger well-controlled trials are warranted to further clarify these relationships.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13676DOI Listing
June 2021

Half of geriatric trauma patients have significant ocular disease: Findings of a novel trauma provider eye examination for vision screening.

J Trauma Acute Care Surg 2021 Jul;91(1):148-153

From the Division of Trauma, Surgical Critical Care and Acute Care Surgery, Department of Surgery (J.M.B., D.J.G., K.C.C., A.W.), West Virginia University; West Virginia University School of Medicine (J.D.); West Virginia University Health Sciences Research and Graduate Education (A.A.); Division of Biostatistics (S.W.), West Virginia University School of Public Health; and Department of Ophthalmology (J.N., A.B.), West Virginia University, Morgantown, West Virginia.

Background: Geriatric ground level fall is a common admission diagnosis for trauma centers in the United States. Visual health has been linked to fall risk reduction in older adult but is rarely fully evaluated during a trauma admission. Using a commercial application and a questionnaire, we developed and tested a trauma provider eye examination (TPEE) to screen visual health. This study used the TPEE to (1) evaluate the prevalence of undiagnosed or undertreated visual disease in geriatric trauma patients and (2) determine the feasibility and reliability of the TPEE to screen for vision disease.

Methods: This prospective study included patients older than 60 years evaluated by the trauma service from June 2019 to May 2020. Patients with ocular or globe trauma were excluded. The primary outcome was significant abnormal vision (SAV) found using the TPEE. Ophthalmology performed a dilated examination as the criterion standard for comparison. We assessed the feasibility and reliability of the TPEE. Fisher's exact test and logistic model were used in the data analysis.

Results: Enrollment concluded with 96 patients. Mean age was 75 years, and fall (79%) was the most common mechanism of injury. Significant abnormal vision was common: undiagnosed disease was found in 39% and undertreated in 14%. Trauma provider examination was 94% sensitive and 92% specific for SAV cases. Congruence between TPEE and ophthalmology examination was highest in pupil examination (86%), visual fields (58%), and Amsler grid (52%). Multivariate analysis found that a combination of an abnormal Amsler test and abnormal visual field defect was significantly associated with SAV (odds ratio, 4.1; p = 0.03).

Conclusion: Trauma provider eye examination screening can identify patients with visual deficits. Given the association between visual deficits and fall risk, older adults may benefit from such a screening or a formal ophthalmology referral.

Level Of Evidence: Therapeutic/Care Management, level II.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0000000000003156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243858PMC
July 2021

Copy number alterations identify a smoking-associated expression signature predictive of poor outcome in head and neck squamous cell carcinoma.

Cancer Genet 2021 Aug 28;256-257:136-148. Epub 2021 May 28.

Department of Biochemistry, Program in Cancer Cell Biology USA. Electronic address:

Cigarette smoking is a risk factor for the development of head and neck squamous cell carcinoma (HNSCC), partially due to tobacco-induced large-scale chromosomal copy-number alterations (CNAs). Identifying CNAs caused by smoking is essential in determining how gene expression from such regions impact tumor progression and patient outcome. We utilized The Cancer Genome Atlas (TCGA) whole genome sequencing data for HNSCC to directly identify amplified or deleted genes correlating with smoking pack-year based on linear modeling. Internal cross-validation identified 35 CNAs that significantly correlated with patient smoking, independent of human papillomavirus (HPV) status. The most abundant CNAs were chromosome 11q13.3-q14.4 amplification and 9p23.1/9p24.1 deletion. Evaluation of patient amplicons reveals four different patterns of 11q13 gene amplification in HNSCC resulting from breakage-fusion-bridge (BFB) events. . Predictive modeling identified 16 genes from these regions that denote poorer overall and disease-free survival with increased pack-year use, constituting a smoking-associated expression signature (SAES). Patients with altered expression of signature genes have increased risk of death and enhanced cervical lymph node involvement. The identified SAES can be utilized as a novel predictor of increased disease aggressiveness and poor outcome in smoking-associated HNSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cancergen.2021.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273756PMC
August 2021

Clinical Characteristics and Outcomes of COVID-19 in West Virginia.

Viruses 2021 05 5;13(5). Epub 2021 May 5.

West Virginia Clinical and Translational Science Institute, Morgantown, WV 26505, USA.

This study examines the clinical characteristics, outcomes and types of management in SARS-CoV-2 infected patients, in the hospitals affiliated with West Virginia University. We included patients from West Virginia with SARS-CoV-2 infection between 15 April to 30 December 2020. Descriptive analysis was performed to summarize the characteristics of patients. Regression analyses were performed to assess the association between baseline characteristics and outcomes. Of 1742 patients, the mean age was 47.5 years (±22.7) and 54% of patients were female. Only 459 patients (26.3%) reported at least one baseline symptom, of which shortness of breath was most common. More than half had at least one comorbidity, with hypertension being the most common. There were 131 severe cases (7.5%), and 84 patients (4.8%) died despite treatment. The mean overall length of hospital stay was 2.6 days (±6.9). Age, male sex, and comorbidities were independent predictors of outcomes. In this study of patients with SARS-CoV-2 infection from West Virginia, older patients with underlying co-morbidities had poor outcomes, and the in-hospital mortality was similar to the national average.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13050835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148202PMC
May 2021

Assessing brain injury topographically using MR neurite orientation dispersion and density imaging in multiple sclerosis.

J Neuroimaging 2021 May 25. Epub 2021 May 25.

Neuroimaging Unit, Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center (VUMC), Nashville, Tennessee, USA.

Background And Purpose: Axonal injury is a key player of disability in persons with multiple sclerosis (pwMS). Yet, detecting and measuring it in vivo is challenging. The neurite orientation dispersion and density imaging (NODDI) proposes a novel framework for probing axonal integrity in vivo. NODDI at 3.0 Tesla was used to quantify tissue damage in pwMS and its relationship with disease progression.

Methods: Eighteen pwMS (4 clinically isolated syndrome, 11 relapsing remitting, and 3 secondary progressive MS) and nine age- and sex-matched healthy controls underwent a brain MRI, inclusive of clinical sequences and a multi-shell diffusion acquisition. Parametric maps of axial diffusivity (AD), neurite density index (ndi), apparent isotropic volume fraction (ivf), and orientation dispersion index (odi) were fitted. Anatomically matched regions of interest were used to quantify AD and NODDI-derived metrics and to assess the relations between these measures and those of disease progression.

Results: AD, ndi, ivf, and odi significantly differed between chronic black holes (cBHs) and T2-lesions, and between the latter and normal appearing white matter (NAWM). All metrics except ivf significantly differed between NAWM located next to a cBH and that situated contra-laterally. Only NAWM odi was significantly associated with T2-lesion volume, the timed 25-foot walk test and disease duration.

Conclusions: NODDI is sensitive to tissue injury but its relationship with clinical progression remains limited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jon.12876DOI Listing
May 2021

COVID-19 and neuroinflammation: a literature review of relevant neuroimaging and CSF markers in central nervous system inflammatory disorders from SARS-COV2.

J Neurol 2021 May 19. Epub 2021 May 19.

Department of Neurology, Wayne State University, Detroit, MI, USA.

Background: The literature on neurological manifestations in COVID-19 patients has been rapidly increasing with the pandemic. However, data on CNS inflammatory disorders in COVID-19 are still evolving. We performed a literature review of CNS inflammatory disorders associated with coronavirus disease-2019 (COVID-19).

Methods: We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords; "SARS-CoV-2 and neurological complication", "SARS-CoV-2 and CNS Complication" looking for reports of transverse myelitis, longitudinally extensive transverse myelitis, neuromyelitis optica, myelitis, Myelin Oligodendrocyte Glycoprotein Antibody Disorder (MOGAD), Acute Disseminated Encephalomyelitis (ADEM), Acute Hemorrhagic Necrotizing Encephalitis/Acute Hemorrhagic Leukoencephalitis (AHNE/AHLE), Cytotoxic lesion of the Corpus Callosum/Mild Encephalopathy Reversible Splenium Lesion(CLOCC/MERS) and Optic neuritis published between December 01, 2019 and March 15, 2021.

Results: Our literature search revealed 43 patients meeting the diagnosis of myelitis, including Transverse Myelitis, ADEM, AHNE/AHLE or CLOCC/MERS and Optic neuritis. Acute myelitis was most commonly associated with non-severe COVID-19 and all reported cases of AHNE/AHLE had severe COVID-19 infection. Based on IDSA/ATS criteria of either requiring vasopressor for septic shock or mechanical ventilation, 49% (n = 18) patients were considered to have a severe COVID infection. There were 7 (n = 19%) fatalities.

Conclusion: To our knowledge, this is among the first reviews that includes the clinical features, neuroimaging, CSF findings and outcomes in COVID-19-associated CNS inflammatory disorders. Our observational review study reveals that although rare, myelitis, ADEM, AHNE and CLOCC can be associated with COVID-19 infection. Further studies using MRI imaging and CSF analysis in early diagnosis and intervention of these disorders are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-021-10611-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131883PMC
May 2021

SMAD4 loss is associated with response to neoadjuvant chemotherapy plus hydroxychloroquine in patients with pancreatic adenocarcinoma.

Clin Transl Sci 2021 May 18. Epub 2021 May 18.

Division of Surgical Oncology, Department of Surgery, West Virginia University, Morgantown, West Virginia, USA.

SMAD4, a tumor suppressor gene, is lost in up to 60%-90% of pancreatic adenocarcinomas (PDAs). Loss of SMAD4 allows tumor progression by upregulating autophagy, a cell survival mechanism that counteracts apoptosis and allows intracellular recycling of macromolecules. Hydroxychloroquine (HCQ) is an autophagy inhibitor. We studied whether HCQ treatment in SMAD4 deficient PDA may prevent therapeutic resistance induced by autophagy upregulation. We retrospectively analyzed the SMAD4 status of patients with PDA enrolled in two prospective clinical trials evaluating pre-operative HCQ. The first dose escalation trial demonstrated the safety of preoperative gemcitabine with HCQ (NCT01128296). More recently, a randomized trial of gemcitabine/nab-paclitaxel +/- HCQ evaluated Evans Grade histopathologic response (NCT01978184). The effect of SMAD4 loss on response to HCQ and chemotherapy was studied for association with clinical outcome. Fisher's exact test and log-rank test were used to assess response and survival. Fifty-two patients receiving HCQ with neoadjuvant chemotherapy were studied. Twenty-five patients had SMAD4 loss (48%). 76% of HCQ-treated patients with SMAD4 loss obtained a histopathologic response greater than or equal to 2A, compared with only 37% with SMAD4 intact (p = 0.006). Although loss of SMAD4 has been associated with worse outcomes, in the current study, loss of SMAD4 was not associated with a detriment in median overall survival in HCQ-treated patients (34.43 months in SMAD4 loss vs. 27.27 months in SMAD4 intact, p = 0.18). The addition of HCQ to neoadjuvant chemotherapy in patients with PDA may improve treatment response in those with SMAD4 loss. Further study of the relationship among SMAD4, autophagy, and treatment outcomes in PDA is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cts.13029DOI Listing
May 2021

Incorporating a Usual Care Comparator into a Study of Meditation and Music Listening for Older Adults with Subjective Cognitive Decline: A Randomized Feasibility Trial.

J Alzheimers Dis Rep 2021 Mar 11;5(1):187-206. Epub 2021 Mar 11.

Department of Communication Sciences and Disorders, West Virginia University HSC, Morgantown, WV, USA.

Background: Recent studies suggest meditation and music listening (ML) may improve cognitive and psychosocial outcomes in adults with subjective cognitive decline (SCD). However, lack of a usual care group has limited conclusions.

Objective: To assess the: 1) feasibility of incorporating an enhanced usual care (EUC) comparator in a trial of Kirtan Kriya meditation (KK) and ML for adults experiencing SCD; and 2) preliminary effects of active treatment (KK/ML) versus an EUC program.

Methods: Forty participants with SCD were randomized 1:1:2 to a 12-week KK, ML, or EUC program. KK and ML participants were asked to practice 12 minutes/day; EUC participants were given a comprehensive educational packet regarding healthy aging and strategies for improving/maintaining brain health and asked to record any activities or strategies used. Feasibility was assessed using measures of retention, adherence, treatment expectancies, and participant satisfaction, as well as information from exit questionnaires and daily practice/activity logs. Cognitive functioning, stress, mood, sleep-quality, and health-related quality of life (QOL) were measured pre- and post-intervention using well-validated instruments.

Results: Thirty-two participants (80%) completed the 3-month study, with retention highest in the EUC group ( < 0.05). Active treatment participants averaged 6.0±0.4 practice sessions/week, and EUC participants, 7.5±0.6 brain health activities/week. Treatment expectancies were similar across groups. EUC participants indicated high satisfaction with the program and study. Despite limited study power, the active treatment group showed significantly greater gains in subjective memory functioning (ps≤0.025) and nonsignificant improvements in cognitive performance (TMT-B), perceived stress, QOL, and mood (ps≤0.08) compared to the EUC group.

Conclusion: Findings of this pilot feasibility trial suggest incorporation of an EUC program is feasible, and that participation in a simple 12-week relaxation program may be helpful for adults with SCD versus engagement in an EUC program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/ADR-200249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075554PMC
March 2021

Capecitabine as Maintenance Therapy for High-Risk, Resected Colorectal Cancer.

Gastrointest Tumors 2021 Apr 10;8(2):81-86. Epub 2021 Mar 10.

Department of Medicine, West Virginia University, Morgantown, West Virginia, USA.

Introduction: In 2020, colorectal cancer will be the fourth most frequently diagnosed malignant neoplasm and the second leading cause of site-specific, cancer-related deaths in the USA. Notably, 80% of the new cases are, by staging criteria, potentially curable even those with completely resected stage 4 disease. If slightly more than half the losses can be attributed to metastatic disease at presentation, then the remaining portion of deaths may be linked to disease relapse after surgery and, if applicable, adjuvant chemotherapy. The inference that these therapies are not curative for a significant number of subjects poses a role for maintenance therapy.

Objective: To assess event-free survival (EFS) of patients who received capecitabine as maintenance therapy following treatment according to current guidelines.

Methods: Clinical outcomes data were collected for 35 subjects treated with capecitabine as maintenance therapy. Descriptive statistical analyses were conducted on collective data related to duration of maintenance therapy and disease or clinical status from surgery to initial event. Kaplan-Meier method and log-rank test were used to analyze EFS and overall survival.

Results: Of the entire cohort, 26 subjects have no evidence of disease (NED), a median of 5.5 years from surgery. Kaplan-Meier analyses indicated a 5-year EFS rate of 74% (95% CI: 60-90%). Eighteen of these 26 patients received capecitabine ≥30 months. Eight of the 17 subjects treated with capecitabine therapy for <30 months developed progressive disease; the majority of the relapses occurred within 20 months of surgery. The difference between the two groups was statistically significant. Six subjects died, only two of who had metastatic disease at the time of death; the other four had NED at least 4 years from surgery. Five patients with resected stage 4 disease who received capecitabine as maintenance therapy were alive >5 years from surgery.

Conclusion: The findings and analyses of this cohort of patients suggest that maintenance capecitabine therapy reduces the risk of disease progression and cancer-related death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000513960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077449PMC
April 2021

Coronavirus testing disparities associated with community level deprivation, racial inequalities, and food insecurity in West Virginia.

Ann Epidemiol 2021 07 2;59:44-49. Epub 2021 Apr 2.

West Virginia Clinical and Translational Sciences Institute, Morgantown, WV; West Virginia University School of Medicine, Morgantown, WV.

Purpose: Social determinants of health and racial inequalities impact healthcare access and subsequent coronavirus testing. Limited studies have described the impact of these inequities on rural minorities living in Appalachia. This study investigates factors affecting testing in rural communities.

Methods: PCR testing data were obtained for March through September 2020. Spatial regression analyses were fit at the census tract level. Model outcomes included testing and positivity rate. Covariates included rurality, percent Black population, food insecurity, and area deprivation index (a comprehensive indicator of socioeconomic status).

Results: Small clusters in coronavirus testing were detected sporadically, while test positivity clustered in mideastern and southwestern WV. In regression analyses, percent food insecurity (IRR = 3.69×10, [796, 1.92×10]), rurality (IRR=1.28, [1.12, 1.48]), and percent population Black (IRR = 0.88, [0.84, 0.94]) had substantial effects on coronavirus testing. However, only percent food insecurity (IRR = 5.98 × 10, [3.59, 1.07×10]) and percent Black population (IRR = 0.94, [0.90, 0.97]) displayed substantial effects on the test positivity rate.

Conclusions: Findings highlight disparities in coronavirus testing among communities with rural minorities. Limited testing in these communities may misrepresent coronavirus incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.annepidem.2021.03.009DOI Listing
July 2021

Sublingual Buprenorphine/Naloxone and Multi-Modal Management for High-Risk Chronic Pain Patients.

J Clin Med 2021 Mar 2;10(5). Epub 2021 Mar 2.

Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine, Morgantown, WV 26506, USA.

Patients with chronic pain managed with opioid medications are at high risk for opioid overuse or misuse. West Virginia University (WVU) established a High-Risk Pain Clinic to use sublingual buprenorphine/naloxone (bup/nal) plus a multimodal approach to help chronic pain patients with history of Substance Use Disorder (SUD) or aberrant drug-related behavior. The objective of this study was to report overall retention rates and indicators of efficacy in pain control from approximately six years of High-Risk Pain Clinic data. A retrospective chart review was conducted for a total of 78 patients who enrolled in the High-Risk Pain Clinic between 2014 and 2020. Data gathered include psychiatric diagnoses, prescribed medications, pain score, buprenorphine/naloxone dosing, time in clinic, and reason for dismissal. A linear mixed effects model was used to assess the pain score from the Defense and Veterans Pain Rating Scale (DVPRS) and daily bup/nal dose across time. The overall retention of the High-Risk Pain Clinic was 41%. The mean pain score demonstrated a significant downward trend across treatment time ( < 0.001), while the opposite trend was seen with buprenorphine dose ( < 0.001). With the benefit of six years of observation, this study supports buprenorphine/naloxone as a safe and efficacious component of comprehensive chronic pain treatment in patients with SUD or high-risk of opioid overuse or misuse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10050973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957677PMC
March 2021

Comparison of the visual outcome between macula-on and macula-off rhegmatogenous retinal detachment based on the duration of macular detachment.

BMJ Open Ophthalmol 2021 11;6(1):e000615. Epub 2021 Mar 11.

Ophthalmology, West Virginia University, Morgantown, West Virginia, USA.

Objective: To compare the visual outcomes between macula-on and macula-off primary rhegmatogenous retinal detachment (RRD) based on the duration of macular detachment (DMD).

Methods And Analysis: Retrospective study including 96 eyes with RRD (34 macula-on and 62 macula-off) repaired between June 2012 and March 2020. The final visual acuity (VA) was compared after the patients were divided by the status of the macula and their DMD.

Results: The mean final VA of patients with macula-on RRD (group A) was logarithm of the minimum angle of resolution (logMAR) 0.04±0.07, which was not statistically different from that of individuals with macula-off RRD with DMD ≤3 days (group B; logMAR 0.05±0.06) (p=0.79). There were statistically significant differences in the final VA between group A and patients with macula-off RRD with DMD of 4-7 days (group C; logMAR 0.15±0.15) (p=0.017) as well as between group A and those with macula-off RRD with DMD ≥8 days (group D; logMAR 0.36±0.29) (p<0.001). There was no significant difference in the final VA between group B and C (p=0.33).

Conclusion: The mean final VA of patients with macula-on RRD was comparable to that of the macula-off patients with DMD ≤3 days. Our findings suggest that if macula-on RRD could not be immediately repaired, a repair within 72 hours may result in similar outcomes, even if the macula detaches within that time frame. However, once the macula detaches, we do not observe statistically significant differences in outcome for repairs done within 7 days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjophth-2020-000615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957123PMC
March 2021

Perilesional neurodegenerative injury in multiple sclerosis: Relation to focal lesions and impact on disability.

Mult Scler Relat Disord 2021 Apr 5;49:102738. Epub 2021 Jan 5.

Neuroimaging Unit, Neuro-immunology Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Neurology, VA Hospital, TN Valley Healthcare System, Nashville, TN, USA. Electronic address:

Background: Axonal injury is the primary source of irreversible neurological decline in persons with multiple sclerosis (pwMS). Identifying and quantifying myelin and axonal loss in lesional and perilesional tissue in vivo is fundamental for a better understanding of multiple sclerosis (MS) outcomes and patient impairment. Using advanced magnetic resonance imaging (MRI) methods, consisting of selective inversion recovery quantitative magnetization transfer imaging (SIR-qMT) and multi-compartment diffusion MRI with the spherical mean technique (SMT), we conducted a cross-sectional pilot study to assess myelin and axonal damage in the normal appearing white matter (NAWM) surrounding chronic black holes (cBHs) and how this pathology correlates with disability in vivo. We hypothesized that lesional axonal transection propagates tissue injury in the surrounding NAWM and that the degree of this injury is related to patient disability.

Methods: Eighteen pwMS underwent a 3.0 Tesla conventional clinical MRI, inclusive of T1 and T2 weighted protocols, as well as SIR-qMT and SMT. Regions of interests (ROIs) were manually delineated in cBHs, NAWM neighboring cBHs (perilesional NAWM), distant ipsilateral NAWM and contra-lateral distant NAWM. SIR-qMT-derived macromolecular-to-free pool size ratio (PSR) and SMT-derived apparent axonal volume fraction (V) were extracted to infer on myelin and axonal content, respectively. Group differences were assessed using mixed-effects regression models and correlation analyses were obtained by bootstrapping 95% confidence interval.

Results: In comparison to perilesional NAWM, both PSR and V values were reduced in cBHs (p < 0.0001) and increased in distant contra-lateral NAWM ROIs (p < 0.001 for PSR and p < 0.0001 for V) but not ipsilateral NAWM (p = 0.176 for PSR and p = 0.549 for V). V values measured in cBHs correlated with those in perilesional NAWM (Pearson rho = 0.63, p < 0.001). No statistically relevant associations were seen between PSR/V values and clinical and/or MRI metrics of the disease with the exception of cBH PSR values, which correlated with the Expanded Disability Status Scale (Pearson rho = -0.63, p = 0.03).

Conclusions: Our results show that myelin and axonal content, detected by PSR and V, are reduced in perilesional NAWM, as a function of the degree of focal cBH axonal injury. This finding is indicative of an ongoing anterograde/retrograde degeneration and suggests that treatment prevention of cBH development is a key factor for preserving NAWM integrity in surrounding tissue. It also suggests that measuring changes in perilesional areas over time may be a useful measure of outcome for proof-of-concept clinical trials on neuroprotection and repair. PSR and V largely failed to capture associations with clinical and MRI characteristics, likely as a result of the small sample size and cross-sectional design, however, longitudinal assessment of a larger cohort may unravel the impact of this pathology on disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2021.102738DOI Listing
April 2021

A Prospective Trial Evaluating the Safety and Systemic Response From the Concurrent Use of Radiation Therapy with Checkpoint Inhibitor Immunotherapy in Metastatic Non-Small Cell Lung Cancer.

Clin Lung Cancer 2021 Jan 25. Epub 2021 Jan 25.

WVU Cancer Institute, West Virginia University, Morgantown, WV.

Introduction/background: This study assessed the safety and systemic (abscopal) response from the addition of local stereotactic body radiation therapy (SBRT) to checkpoint inhibitor (CPI) immunotherapy in patients with metastatic non-small cell lung cancer.

Patients/methods: Thirty-five patients with at least 2 sites of measurable disease on PET/CT received standard-of-care CPI immunotherapy alone (n = 19), or in combination with 4 cycles doublet carboplatin/pemetrexed chemotherapy (n = 16), and 3 to 5 fractions SBRT to a single extracranial target lesion between cycles 1 to 2 of the systemic therapy. Adverse events were assessed using CTCAE version 5.0. Best systemic objective response rate (ORR) was assessed using iRECIST criteria, excluding any irradiated lesion(s). Additional SBRT to a different target lesion was offered to patients who continued on immunotherapy with unconfirmed progressive disease or mixed response.

Results: Fifteen patients (44%) experienced 22 grade 1 to 2 toxicities potentially attributable to radiation, most commonly pneumonitis (n = 9) and fatigue (n = 6), and no grade 3 to 5 radiation-induced toxicities. Patients undergoing combined CPI-chemotherapy received a lower median biologically effective dose of SBRT than those undergoing CPI monotherapy (43.2 vs. 60Gy), but had a higher rate of radiation-induced toxicity (56% vs. 32%, P < .01). The best systemic ORR was 53%, with 20.5% stable disease and 26.5% progressive disease. Fifteen patients underwent a subsequent course of SBRT based on their response, among which 3 (20%) had progression-free intervals of 12, 16, and 10 months thereafter.

Conclusions: Addition of SBRT to CPI immunotherapy (with/without chemotherapy) is safe. The favorable systemic response observed warrants further assessment with a randomized trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2021.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310528PMC
January 2021

Prescription drug monitoring program policy reform: human and veterinary practitioner prescribing in West Virginia, 2008-2020.

J Public Health Policy 2021 Jun 12;42(2):249-257. Epub 2021 Feb 12.

Department of Epidemiology, West Virginia University, 64 Medical Center Dr., Morgantown, WV, 26506, USA.

No study has examined Prescription Drug Monitoring Program (PDMP) data for West Virginia or among specialty practices, such as veterinary medicine. The objectives of this study were to conduct time series modeling to describe the PDMP policy reform impact on prescribing rates for human and veterinary providers. We obtained data from the WV PDMP for 2008 through 2020 for the number of opioid prescriptions filled and providers. We estimated prescribing rates for human and veterinary providers separately based upon the top five opioids prescribed by veterinarians. We estimated temporal effects using a Bayesian log-normal time series model for humans and veterinarians separately. Throughout the study period prescribing rates increased significantly for veterinarians, and decreased for human providers, particularly during 2018 after implementation of the Opioid Reduction Act. Findings provide novel insight into the differential impact of policy on specialty practices and highlight decreasing human opioid prescribing observed elsewhere.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1057/s41271-021-00275-0DOI Listing
June 2021

Relevance and Clinical Significance of Magnetic Resonance Imaging of Neurological Manifestations in COVID-19: A Systematic Review of Case Reports and Case Series.

Brain Sci 2020 Dec 21;10(12). Epub 2020 Dec 21.

Department of Neurology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA.

We performed a systematic literature review of neuroimaging, predominantly focusing on magnetic resonance imaging (MRI) findings associated with neurological manifestations of coronavirus disease-2019 (COVID-19). We screened articles from PubMed, Google Scholar and Scopus, looking for reports that would potentially have neuroimaging findings in patients with COVID-19. Data analysis was performed with patient-based data based on the availability of clinical characteristics and outcomes for each individual patient from the studies. Chi square and Wilcoxon rank-sum tests were used to report COVID-19 severity and outcomes based on neurological imaging indicators and pathophysiology. A total of 171 patients with COVID-19 having neurological complications, from 134 studies, were identified in our review. The most common neuroimaging finding was ischemic stroke (62, 36.2%) cases, followed by CNS inflammatory disorder (44, 25.7%), and hemorrhagic stroke (41, 24.0%). Around 51% of all the fatal COVID-19 cases had an ischemic stroke. Among patients with ischemic stroke, the mean age of those who suffered from COVID-19 infection was 57.5 years (SD = 15.4) whereas it was 50.7 years (SD = 15.1) among those without stroke/other diagnosis. Fatality was more common in patients with ischemic stroke compared to those with other diagnosis (40% vs. 22%, = 0.011). The most frequently published neuroimaging findings in patients with COVID-19 were ischemic stroke, CNS inflammatory disorder, and hemorrhagic disorder. In those studies, ischemic stroke was associated with fatality, and was more frequently seen in older patients. Based on our findings, early usage of MRI in COVID-19 patients may be recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci10121017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766893PMC
December 2020

High prevalence of co-occurring substance use in individuals with opioid use disorder.

Addict Behav 2021 03 4;114:106752. Epub 2020 Dec 4.

West Virginia University School of Medicine (WVU SOM), Morgantown, WV 26505, USA; West Virginia Clinical and Translational Science Institute, Morgantown, WV 26505, USA.

Objective: Funding to address the current opioid epidemic has focused on treatment of opioid use disorder (OUD); however, rates of other substance use disorders (SUDs) remain high and non-opioid related overdoses account for nearly 30% of overdoses. This study assesses the prevalence of co-occurring substance use in West Virginia (WV) to inform treatment strategies. The objective of this study was to assess the prevalence of, and demographic and clinical characteristics (including age, gender, hepatitis C virus (HCV) status) associated with, co-occurring substance use among patients with OUD in WV.

Methods: This retrospective study utilized the West Virginia Clinical and Translation Science Institute Integrated Data Repository, comprised of Electronic Medical Record (EMR) data from West Virginia University Medicine. Deidentified data were extracted from inpatient psychiatric admissions and emergency department (ED) healthcare encounters between 2009 and 2018. Eligible patients were those with OUD who had a positive urine toxicology screen for opioids at the time of their initial encounter with the healthcare system. Extracted data included results of comprehensive urine toxicology testing during the study timeframe.

Results: 3,127 patients met the inclusion criteria of whom 72.8% had co-occurring substance use. Of those who were positive for opioids and at least one additional substance, benzodiazepines were the most common co-occurring substances (57.4% of patients yielded a positive urine toxicology screen for both substances), followed by cannabis (53.1%), cocaine (24.5%) and amphetamine (21.6%). Individuals who used co-occurring substances were younger than those who were positive for opioids alone (P < 0.001). There was a higher prevalence of individuals who used co-occurring substances that were HCV positive in comparison to those who used opioids alone (P < 0.001). There were limited gender differences noted between individuals who used co-occurring substances and those who used opioids alone. Among ED admissions who were positive for opioids, 264 were diagnosed with substance toxicity/overdose, 78.4% of whom had co-occurring substance use (benzodiazepines: 65.2%; cannabis: 44.4%; cocaine: 28.5%; amphetamine: 15.5%). Across the 10-year timespan, the greatest increase for the entire sample was in the rate of co-occurring amphetamine and opioid use (from 12.6% in 2014 to 47.8% in 2018).

Conclusions: These data demonstrate that the current substance use epidemic extends well beyond opioids, suggesting that comprehensive SUD prevention and treatment strategies are needed, especially for those substances which do not yet have any evidence-based and/or medication treatments available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.addbeh.2020.106752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934179PMC
March 2021

Pathologic Fibrinolysis is More Common in a Rural Trauma Setting.

Am Surg 2020 Dec 15:3134820973726. Epub 2020 Dec 15.

Department of Surgery, Division of Trauma, Acute Care Surgery and Surgical Critical Care, 53422West Virginia University, Morgantown, WV, USA.

Introduction: Fibrinolysis (lysis) has been extensively studied in trauma patients. Many studies on the distribution of lysis phenotype have been conducted in setting with short prehospital time. This study aimed to evaluate the distribution of lysis phenotypes in a population with prolonged prehospital times in a rural environment.

Methods: A retrospective study was performed at an American College of Surgeons-verified level 1 trauma center, serving a large rural population. Full trauma team activations from January 1, 2017 to August 31, 2018 were evaluated, and all patients with an ISS>15 analyzed. Thromboelastography was routinely performed on all participants on arrival. Lysis phenotypes were classified based on LY30 results: shutdown (≤.8%), physiologic (.9-2.9%), and hyper (>2.9%).

Results: 259 patients were evaluated, 134 (52%) presented direct from the scene. For scene patients, lysis distribution was 24% physiologic, 49% shutdown, and 27% hyper. Transferred patients demonstrated a reduction in physiologic lysis to 14% ( = .03), shutdown present in 66%, and hyper in 20%. Empiric prehospital tranexamic acid was given to 18 patients, physiologic lysis was present in 6%, shutdown 72%, and hyper 22%; this increase was not statistically significant ( = .5).

Conclusion: Fibrinolysis phenotypes are not consistent across all trauma populations. This study showed rural trauma patients had a significantly increased rate of pathologic lysis. This was consistent for scene and transfer patients who received care at another facility prior to arrival for definitive care. Future studies to evaluate the factors influencing these differences are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003134820973726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203746PMC
December 2020

Predictors of diabetes risk perception among college students.

J Am Coll Health 2020 Oct 13:1-7. Epub 2020 Oct 13.

Department of Biostatistics, School of Public Health, West Virginia University, Morgantown, West Virginia, USA.

Objective: To explore the diabetes knowledge and future disease risk perception of college students. 697 college students were purposefully recruited at a large state university and completed an online survey. Diabetes knowledge, future disease risk perception, lifestyle, and demographic factors were assessed. The majority of students (56%) reported a family history of diabetes but perceived their diabetes risk as low/moderate (90%). Logistic regression indicated higher knowledge (OR, 1.07; 95% CI, 1.01-1.13), age (OR, 1.08; 95% CI, 1.00-1.16), bodymassindex (BMI) (OR, 4.90; 95% CI, 2.33-10.30) and family history of diabetes (OR, 4.30; 95% CI, 1.97-9.40) increased perception of future diabetes risk. Those who self-rated their health as good/excellent and read food labels regularly/often had lower perceived future risk of diabetes. Results highlight the importance of educating college students on diabetes risk factors as well as primary/secondary prevention for reducing diabetes incidence in this age group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07448481.2020.1825222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041907PMC
October 2020

Risk factors associated with infection of blood-borne virus among people who used methamphetamine.

BMC Infect Dis 2020 Oct 9;20(1):742. Epub 2020 Oct 9.

Department of Epidemiology, School of Public Health, West Virginia University, One Medical Center Drive, Morgantown, WV, 26506, USA.

Background: The surge of methamphetamine use has been a complicating factor compounding the steeply increasing number of drug overdose deaths in the U.S. Infection from blood-borne viruses including hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV, related to methamphetamine use continue to grow. This study aims to examine the risk factors associated with HBV, HCV and HIV among people who used methamphetamine.

Methods: People who ever used methamphetamine were identified from five National Health and Nutrition Examination Survey (NHANES) cohorts, 2007 to 2016. The outcome was either positive or negative for blood-borne viruses as identified from laboratory tests. Weighted statistics for the combined ten years of data were calculated by multiplying the weighted variable for laboratory measurements by 0.2. We examined the association of sexual activities (sexual partners, sexual identity), drug use behaviors (poly-drug use, injection drug use, frequency of drug use, age started using methamphetamine), demographics, and socio-economic status with blood-borne viruses using bivariate and multivariable logistic regression models.

Results: There were 1132 participants representing approximately 11,996,319 persons who ever used methamphetamine in the U.S. Blood-borne viruses' positive rate was 13.0 per 100,000. Multivariable logistic regression analyses showed significant associations of blood-borne infections with age 40-49 years (vs. age 20-29 years, adjusted odds ratio 4.77, 95% CI 1.11-20.55), age 50-59 years (vs. age 20-29 years, 10.25, 2.40-43.82), living within poverty index 1-1.9 (vs. poverty index > = 2, 2.55; 1.19-5.49), living below the poverty threshold (vs. poverty index > = 2, 2.55; 1.11-5.86), having lower than high school education (vs. equal or higher than high school education, 3.13; 1.51-6.46), sexual identity as other than heterosexual (vs. heterosexual, 5.60; 1.72-18.28), using methamphetamine and heroin and cocaine (vs. using methamphetamine alone, 4.24; 1.06-16.92), injection drug use (vs. no injection drug use, 3.15; 1.61-6.16), and started using methamphetamine at age above 25 (vs. started using methamphetamine at age between 10 and 17, 2.09; 1.01-4.35).

Conclusions: Among people who use methamphetamine, those who use polysubstance, or who inject substances, are in urgent need for vaccination and interventions to avoid further harm from blood borne infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-020-05464-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547473PMC
October 2020

Electrophysiological Evidence of Early Cortical Sensitivity to Human Conspecific Mimic Voice as a Distinct Category of Natural Sound.

J Speech Lang Hear Res 2020 10 16;63(10):3539-3559. Epub 2020 Sep 16.

Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown.

Purpose From an anthropological perspective of hominin communication, the human auditory system likely evolved to enable special sensitivity to sounds produced by the vocal tracts of human conspecifics whether attended or passively heard. While numerous electrophysiological studies have used stereotypical human-produced verbal (speech voice and singing voice) and nonverbal vocalizations to identify human voice-sensitive responses, controversy remains as to when (and where) processing of acoustic signal attributes characteristic of "human voiceness" per se initiate in the brain. Method To explore this, we used animal vocalizations and human-mimicked versions of those calls ("mimic voice") to examine late auditory evoked potential responses in humans. Results Here, we revealed an N1b component (96-120 ms poststimulus) during a nonattending listening condition showing significantly greater magnitude in response to mimics, beginning as early as primary auditory cortices, preceding the time window reported in previous studies that revealed species-specific vocalization processing initiating in the range of 147-219 ms. During a sound discrimination task, a P600 (500-700 ms poststimulus) component showed specificity for accurate discrimination of human mimic voice. Distinct acoustic signal attributes and features of the stimuli were used in a classifier model, which could distinguish most human from animal voice comparably to behavioral data-though none of these single features could adequately distinguish human voiceness. Conclusions These results provide novel ideas for algorithms used in neuromimetic hearing aids, as well as direct electrophysiological support for a neurocognitive model of natural sound processing that informs both neurodevelopmental and anthropological models regarding the establishment of auditory communication systems in humans. Supplemental Material https://doi.org/10.23641/asha.12903839.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1044/2020_JSLHR-20-00063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060013PMC
October 2020

Analysis of patient-specific factors contributing to effectiveness of glucagon-like peptide-1 receptor agonists.

J Am Pharm Assoc (2003) 2020 Nov - Dec;60(6):937-942. Epub 2020 Aug 8.

Background: Glucagon-like peptide-1 receptor (GLP-1) agonists are antidiabetic medications used to improve hemoglobin A1c (HbA1c) and promote weight loss. Per the Veterans Affairs/Department of Defense guidelines for the management of type 2 diabetes, GLP-1 agonists are expected to lower HbA1c by 1%-1.5%. The clinical pharmacy specialist in the women's health primary care clinic at the Louis A. Johnson Veterans Affairs Medical Center noted cases of women started on GLP-1 agonists achieving greater than expected HbA1c reduction.

Objectives: The primary objective of this study was to determine if there are any patient-specific factors that may increase the effectiveness of GLP-1 agonists. Secondary objectives included an analysis of average weight and HbA1c, use of the Pearson rank correlation test to determine if there is a correlation between weight change and HbA1c reduction, and an analysis of HbA1c reduction associated with each GLP-1 agonist prescribed.

Methods: A retrospective chart review was conducted. Data collected from the charts included age, sex, height, GLP-1 agonist prescribed, and HbA1c and weight before and after GLP-1 agonist initiation. For primary outcomes, statistical analyses were run between 2 groups: patients who had an HbA1c reduction of greater than 1.5% and patients who had an HbA1c reduction less than or equal to 1.5%.

Results: Women were more likely to have an HbA1c reduction of greater than 1.5% (P = 0.001). Patients with a lower baseline weight were more likely to attain an HbA1c reduction greater than 1.5% (P = 0.045). Higher baseline HbA1c was correlated with an increased likelihood of HbA1c reduction greater than 1.5% (P = 0.001).

Conclusion: GLP-1 agonists may be more effective at reducing HbA1c in female patients, those with a lower baseline weight, and those with a higher baseline HbA1c.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.japh.2020.06.023DOI Listing
June 2021

Intraoperative Radiation Therapy Versus Whole Breast Radiation for Early-Stage Breast Cancer Treatment in Rural Appalachia.

Am Surg 2020 Dec 10;86(12):1666-1671. Epub 2020 Aug 10.

24041 Department of Surgery, West Virginia University, Morgantown, WV, USA.

Background: Intraoperative radiation therapy (IORT) is an alternate accelerated form of radiation following breast-conserving surgery (BCS). Lack of data regarding long-term outcomes has limited adoption. We report our experience with IORT in patients undergoing BCS versus whole breast radiation therapy (WBRT).

Methods: Retrospective review of patients undergoing BCS with IORT versus WBRT (2012-2017). Inclusion: low grade, T1-2N0M0, estrogen receptor/progesterone receptor positive, and Her2-negative infiltrating ductal carcinomas. IORT was delivered as a single fraction of radiation (20 Gy) intraoperatively. Outcomes were compared using Fisher's test for discrete variables or Wilcoxon signed-rank test for continuous variables. Kaplan-Meier method was used to estimate disease-free survival (DFS).

Results: Fifty-one patients (44%) received IORT, and 66 (56%) received WBRT. There was no difference in age, tumor size, receptor status, or in-breast recurrence (1.9% vs 0%, all > .05). Length of follow-up was longer in the WBRT group due to time to inception of IORT (mean ± SD: 44 ± 8.1 vs 73 ± 13 months, < .001). There was no difference in DFS between the 2 groups (HR 2.5; = .44). IORT patients experienced delay to BCS (mean ± SD: 38 ± 12.7 vs 27 ± 12.2 days, < .001) likely due to coordination of care. Analysis demonstrated IORT patients would have traveled a mean distance of 20 miles to the closest WBRT center (range 1-70, miles) for a mean travel time of 31 minutes (range 4-90, minutes) per WBRT treatment.

Discussion: IORT produces noninferior oncologic outcomes and decreased skin toxicity compared with WBRT. It can be convenient for patients in rural regions with limited health care access.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003134820940735DOI Listing
December 2020

Prospective assessment of Clostridioides (formerly Clostridium) difficile colonization and acquisition in hematopoietic stem cell transplant patients.

Transpl Infect Dis 2020 Dec 16;22(6):e13438. Epub 2020 Aug 16.

Department of Pharmacy, West Virginia University Medicine, Morgantown, WV, USA.

Background: Patients undergoing hematopoietic stem cell transplant (HSCT) possess numerous risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) and experience a high rate of diarrhea. Colonization rates of Clostridium difficile vary greatly among subgroup analyses with recent studies demonstrating colonization rates in the blood and marrow transplant units up to nine times that of the general population.

Methods: The primary objectives of this study were to identify the rate of C difficile colonization and acquisition in HSCT patients admitted to the blood and marrow transplant unit. This was a prospective study that included all adult patients admitted for hematopoietic stem cell transplantation. Stool specimens were routinely collected on admission and weekly thereafter for a maximum of six samples per patient.

Results: Forty-two patients met inclusion criteria and had baseline samples available for analysis. The rate of C difficile colonization on admission was 24%, and an additional 9% of patients acquired the organism during admission. Twelve percent of patients developed CDI that was diagnosed clinically. Univariate analysis showed an increased risk of colonization for patients with three or more prior chemotherapy cycles.

Conclusions: Given high colonization rates coupled with high risk of CDI in this population, providers must be judicious when testing for CDI and interpreting test results for HSCT patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13438DOI Listing
December 2020
-->