Publications by authors named "Clark R Andersen"

74 Publications

High molecular weight sodium hyaluronate improves survival of syndecan-1-deficient septic mice by inhibiting neutrophil migration.

PLoS One 2021 30;16(4):e0250327. Epub 2021 Apr 30.

Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America.

Methods: Sepsis was induced by cotton smoke inhalation followed by intranasal administration of Pseudomonas aeruginosa in female (> 6 months) Balb/c and syndecan-1 knockout mice. Survival of mice, lung capillary endothelial glycocalyx integrity, lung water content, and vascular hyper-permeability were determined with or without HMW-SH treatment in these mice. Effects of HMW-SH on endothelial permeability and neutrophil migration were tested in in vitro setting.

Results: In septic wildtype mice, we found a severely damaged pulmonary microvascular endothelial glycocalyx and elevated levels of shed syndecan-1 in the circulation. These changes were associated with significantly increased pulmonary vascular permeability. In septic syndecan-1 knockout mice, extravascular lung water content was higher, and early death was observed. The administration of HMW-SH significantly reduced mortality and lung water content in septic syndecan-1 knockout mice, but not in septic wildtype mice. In in vitro setting, HMW-SH inhibited neutrophil migration and reduced cultured endothelial cell permeability increases. However, these effects were reversed by the addition of recombinant syndecan-1 ectodomain.

Conclusions: HMW-SH reduced lung tissue damage and mortality in the absence of syndecan-1 protein, possibly by reducing vascular hyper-permeability and neutrophil migration. Our results further suggest that increased shed syndecan-1 protein levels are linked with the inefficiency of HMW-SH in septic wildtype mice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250327PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087021PMC
April 2021

Influencers of the Decision to Undergo Contralateral Prophylactic Mastectomy among Women with Unilateral Breast Cancer.

Cancers (Basel) 2021 Apr 23;13(9). Epub 2021 Apr 23.

Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

(1) Background: The relatively high rate of contralateral prophylactic mastectomy (CPM) among women with early stage unilateral breast cancer (BC) has raised concerns. We sought to assess the influence of partners, physicians, and the media on the decision of women with unilateral BC to undergo CPM and identify clinicopathological variables associated with the decision to undergo CPM. (2) Patients and Methods: Women with stage 0 to III unilateral BC who underwent CPM between January 2010 and December 2017. Patients were surveyed regarding factors influencing their self-determined decision to undergo CPM. Partner, physician, and media influence factors were modeled by logistic regressions with adjustments for a family history of breast cancer and pathological stage. (3) Results: 397 (29.6%) patients completed the survey and were included in the study. Partners, physicians, and the media significantly influenced patients' decision to undergo CPM. The logistic regression models showed that, compared to self-determination alone, overall influence on the CPM decision was significantly higher for physicians ( = 0.0006) and significantly lower for partners and the media ( < 0.0001 for both). Fifty-nine percent of patients' decisions were influenced by physicians, 28% were influenced by partners, and only 17% were influenced by the media. The model also showed that patients with a family history of BC had significantly higher odds of being influenced by a partner than did those without a family history of BC ( = 0.015). (4) Conclusions: Compared to self-determination, physicians had a greater influence and partners and the media had a lower influence on the decision of women with unilateral BC to undergo CPM. Strong family history was significantly associated with a patient's decision to undergo CPM.
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http://dx.doi.org/10.3390/cancers13092050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123066PMC
April 2021

Microbiota Detection Patterns Correlate With Presence and Severity of Barrett's Esophagus.

Front Cell Infect Microbiol 2021 23;11:555072. Epub 2021 Feb 23.

Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX , United States.

Background: The microbiome has been increasingly associated with different disease processes, but its role in esophagus is largely unknown. Our goal was to determine the associations of the esophageal microbiota with Barrett's esophagus.

Methods: A total of 74 patients were included in this prospective study, including 34 patients with Barrett's esophagus and 40 patients without Barrett's esophagus. Esophageal swabs were obtained from the uvula, and mucosal biopsies were obtained from the proximal esophagus and distal esophagus in each patient. The microbiome of each sample was assessed using a customized Esophageal Microbiome qPCR array (EMB). For each clinical sample, we completed a detection/non-detection analysis for each organism in the EMB. The limit of detection (LOD) for each target was established by analysis of plasmid dilutions.

Results: Average age was 60.2 years. There were significantly different microbial detection patterns in patients with Barrett's esophagus compared to the control population. There were a greater number of organisms which had different likelihoods of detection in the distal esophagus, compared to the proximal esophagus or uvula. In addition, as the length of the Barrett's column increased, multiple organisms were less likely to be detected. This decreased likelihood occurred only in the distal esophagus. Beside Barrett's esophagus, no other demographic factors were associated with differences in detection patterns.

Conclusions: Microbial community structures differ between patients with and without Barrett's esophagus. Certain organisms are less likely to be detected as the severity of Barrett's esophagus worsens. These results suggest that particular organisms may have a protective effect against the development of Barrett's esophagus.
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http://dx.doi.org/10.3389/fcimb.2021.555072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942024PMC
June 2021

Role of mutational reversions and fitness restoration in Zika virus spread to the Americas.

Nat Commun 2021 01 26;12(1):595. Epub 2021 Jan 26.

World Reference Center for Emerging Viruses and Arboviruses, Institute for Human Infections and Immunity, and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.

Zika virus (ZIKV) emerged from obscurity in 2013 to spread from Asia to the South Pacific and the Americas, where millions of people were infected, accompanied by severe disease including microcephaly following congenital infections. Phylogenetic studies have shown that ZIKV evolved in Africa and later spread to Asia, and that the Asian lineage is responsible for the recent epidemics in the South Pacific and Americas. However, the reasons for the sudden emergence of ZIKV remain enigmatic. Here we report evolutionary analyses that revealed four mutations, which occurred just before ZIKV introduction to the Americas, represent direct reversions of previous mutations that accompanied earlier spread from Africa to Asia and early circulation there. Our experimental infections of Aedes aegypti mosquitoes, human cells, and mice using ZIKV strains with and without these mutations demonstrate that the original mutations reduced fitness for urban, human-amplifed transmission, while the reversions restored fitness, increasing epidemic risk. These findings include characterization of three transmission-adaptive ZIKV mutations, and demonstration that these and one identified previously restored fitness for epidemic transmission soon before introduction into the Americas. The initial mutations may have followed founder effects and/or drift when the virus was introduced decades ago into Asia.
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http://dx.doi.org/10.1038/s41467-020-20747-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838395PMC
January 2021

Omega-7 oil increases telomerase activity and accelerates healing of grafted burn and donor site wounds.

Sci Rep 2021 Jan 13;11(1):975. Epub 2021 Jan 13.

Department of Anesthesiology, Medical Branch, University of Texas, 301 University Blvd, Galveston, TX, 77555-1102, USA.

This study investigated the efficacy of Omega-7 isolated from the sea buckthorn oil (Polyvit Co., Ltd, Gangar Holding, Ulaanbaatar, Mongolia) in ovine burn wound healing models. In vitro, proliferation (colony-forming rate) and migration (scratch) assays using cultured primary ovine keratinocytes were performed with or without 0.025% and 0.08% Omega-7, respectively. The colony-forming rate of keratinocytes in the Omega-7 group at 72 and 96 h were significantly higher than in the control (P < 0.05). The percentage of closure in scratch assay in the Omega-7 group was significantly higher than in the control at 17 h (P < 0.05). In vivo, efficacy of 4% Omega-7 isolated from buckthorn oil was assessed at 7 and 14 days in grafted ovine burn and donor site wounds. Telomerase activity, keratinocyte growth factor, and wound nitrotyrosine levels were measured at day 14. Grafted sites: Un-epithelialized raw surface area was significantly lower and blood flow was significantly higher in the Omega-7-treated sites than in control sites at 7 and 14 days (P < 0.05). Telomerase activity and levels of keratinocyte growth factors were significantly higher in the Omega-7-treated sites after 14 days compared to those of control (P < 0.05). The wound 3-nitrotyrosine levels were significantly reduced by Omega-7. Donor sites: the complete epithelialization time was significantly shorter and blood flow at day 7 was significantly higher in the Omega-7-treated sites compared to control sites (P < 0.05). In summary, topical application of Omega-7 accelerates healing of both grafted burn and donor site wounds. Omega-7 should be considered as a cost-efficient and effective supplement therapy for burn wound healing.
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http://dx.doi.org/10.1038/s41598-020-79597-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806965PMC
January 2021

Inflammatory Myositis in Cancer Patients Receiving Immune Checkpoint Inhibitors.

Arthritis Rheumatol 2021 05 1;73(5):866-874. Epub 2021 Apr 1.

University of Texas MD Anderson Cancer Center, Houston.

Objective: To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes.

Methods: We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available.

Results: A total of 9,088 patients received an ICI. Thirty-six patients (0.40%) were identified as having ICI-myositis: 17 patients (47%) with ICI-myositis alone and 19 (53%) with overlap manifestations (5 patients with myocarditis, 5 with myasthenia gravis, and 9 with both). The incidence of ICI-myositis was 0.31% in those receiving ICI monotherapy and 0.94% in those receiving combination ICI therapy (relative risk 3.1 [95% confidence interval 1.5-6.1]). Twenty-five patients (69%) received ≥1 treatment in addition to glucocorticoids: plasmapheresis in 17 patients (47%), intravenous immunoglobulin in 12 (33%), and biologics in 11 (31%). Patients with overlap conditions had worse outcomes than those with myositis alone, and 79% of them developed respiratory failure. Eight patients died as a result of ICI-myositis, and all had overlap syndrome with myasthenia gravis or myocarditis (P < 0.05); 75% of these patients had a concomitant infection.

Conclusion: ICI-myositis is a rare but severe adverse event. More than half of the patients presented with overlap manifestations and had deleterious outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies have yet to be determined.
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http://dx.doi.org/10.1002/art.41604DOI Listing
May 2021

Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Kidney: The MD Anderson Cancer Center Experience.

Cancers (Basel) 2020 Oct 11;12(10). Epub 2020 Oct 11.

Department of Pediatrics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Limited information exists on the clinical behavior of the Ewing sarcoma family of tumors (ESFT) of the kidney. We reviewed the records of 30 patients (aged 8-69 years) with ESFT of the kidney seen at our institution between 1990 and 2013. We analyzed the event-free survival (EFS) and overall survival (OS) for associations with patient demographics, disease group, tumor size, tumor thrombus, and treatment. Six patients (20%) had tumors confined to the kidney (Group I), seven (23.3%) had local tumor extension beyond the kidney (Group II), and 17 (56.7%) had distant metastasis at diagnosis (Group III). Twenty-five (83.3%) patients underwent radical (19 upfront, five delayed) or partial (one upfront) nephrectomy, 25 (83.3%) chemotherapy and four (13.3%) radiotherapy. The 4-year EFS and OS were 43% (95% CI, 26-61%) and 63% (95% CI, 46-81%), respectively. EFS and OS were significantly associated with disease group and chemotherapy ( < 0.039). The presence of tumor thrombus in renal vein and/or inferior vena cava was associated with worse EFS ( = 0.053). Patients with disease confined to the kidney treated with nephrectomy and adjuvant chemotherapy have favorable outcomes. Local tumor extension beyond the kidney, tumor thrombus, and distant metastasis are unfavorable factors that warrant intensification or novel approaches of therapy.
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http://dx.doi.org/10.3390/cancers12102927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599660PMC
October 2020

Accelerated Failure Time Survival Model to Analyze Morris Water Maze Latency Data.

J Neurotrauma 2021 02 19;38(4):435-445. Epub 2020 Oct 19.

The Moody Project for Translational Traumatic Brain Injury Research, University of Texas Medical Branch, Galveston, Texas, USA.

Traumatic brain injury (TBI) induces cognitive deficits clinically and in animal models. Learning and memory testing is critical when evaluating potential therapeutic strategies and treatments to manage the effects of TBI. We evaluated three data analysis methods for the Morris water maze (MWM), a learning and memory assessment widely used in the neurotrauma field, to determine which statistical tool is optimal for MWM data. Hidden platform spatial MWM data aggregated from three separate experiments from the same laboratory were analyzed using 1) a logistic regression model, 2) an analysis of variance (ANOVA) model, and 3) an accelerated failure time (AFT) time-to-event model. The logistic regression model showed no significant evidence of differences between treatments among any swims over all days of the study,  > 0.11. Although the ANOVA model found significant evidence of differences between sham and TBI groups on three out of four swims on the third day, results are potentially biased due to the failure of this model to account for censoring. The time-to-event AFT model showed significant differences between sham and TBI over all swims on the third day,  < 0.045, taking censoring into account. We suggest AFT models should be the preferred analytical methodology for latency to platform associated with MWM studies.
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http://dx.doi.org/10.1089/neu.2020.7089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875609PMC
February 2021

Impact of Lagtime, Health Insurance Type, and Income Status at Diagnosis on the Long-Term Survival of Adolescent and Young Adult Cancer Patients.

J Adolesc Young Adult Oncol 2021 Apr 14;10(2):164-174. Epub 2020 Jul 14.

Division of Pediatrics and Patient Care, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Delays in diagnosis can affect the short-term survival outcomes of adolescent and young adult (AYA) cancer patients. We sought to determine the extent to which delayed diagnosis, health insurance type, and income status are associated with the long-term survival of AYA cancer patients. We reviewed an institutional cohort of 268 patients age 15-29 years who were diagnosed with the most common neoplasms of the AYA population between 2001 and 2003. We grouped patients by the time of onset of cancer symptomatology to verified diagnosis (lagtime to diagnosis; short or long), health insurance type at diagnosis (public or private), zip-code-based median household income (≤U.S. $50,000 or >U.S. $50,000), and demographic variables. Overall survival (OS) and late OS (LOS; the time from the 5-year anniversary of cancer diagnosis to death from any cause) were the outcomes of interest. OS and LOS did not differ between those with short or long lagtimes to diagnosis for all cancer and for specific cancer types. Among patients with long lagtimes, those with private insurance had significantly better LOS than those with public insurance ( = 0.03). Compared with those who had public insurance, patients who had private insurance at diagnosis had significantly better LOS ( = 0.008). Patients with household incomes >U.S. $50,000 had better LOS than those with household incomes ≤U.S. $50,000 ( = 0.02). Patients with public insurance and household incomes ≤U.S. $50,000 had the poorest LOS. AYA cancer patients with either public health insurance or a low household income at diagnosis are at risk of an inferior LOS.
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http://dx.doi.org/10.1089/jayao.2020.0041DOI Listing
April 2021

Superior Effects of Nebulized Epinephrine to Nebulized Albuterol and Phenylephrine in Burn and Smoke Inhalation-Induced Acute Lung Injury.

Shock 2020 12;54(6):774-782

Department of Anesthesiology, The University of Texas Medical Branch, Galveston, Texas.

The severity of burn and smoke inhalation-induced acute lung injury (BSI-ALI) is associated with alveolar and interstitial edema, bronchospasm, and airway mucosal hyperemia. Previously, we have reported beneficial effects of epinephrine nebulization on BSI-ALI. However, the underlying mechanisms of salutary effects of nebulized epinephrine remain unclear. The present study compared the effects of epinephrine, phenylephrine, and albuterol on a model of BSI-ALI. We tested the hypothesis that both α1- and β2-agonist effects are required for ameliorating more efficiently the BSI-ALI. Forty percent of total body surface area, 3rd-degree cutaneous burn, and 48-breaths of cotton smoke inhalation were induced to 46 female Merino sheep. Postinjury, sheep were mechanically ventilated and cardiopulmonary hemodynamics were monitored for 48 h. Sheep were allocated into groups: control, n = 17; epinephrine, n = 11; phenylephrine, n = 6; and albuterol, n = 12. The drug nebulization began 1 h postinjury and was repeated every 4 h thereafter. In the results, epinephrine group significantly improved oxygenation compared to other groups, and significantly reduced pulmonary vascular permeability index, lung wet-to-dry weight ratio, and lung tissue growth factor-β1 level compared with albuterol and control groups. Epinephrine and phenylephrine groups significantly reduced trachea wet-to-dry weight ratio and lung vascular endothelial growth factor-A level compared with control group. Histopathologically, epinephrine group significantly reduced lung severity scores and preserved vascular endothelial-cadherin level in pulmonary arteries. In conclusion, the results of our studies suggest that nebulized epinephrine more effectively ameliorated the severity of BSI-ALI than albuterol or phenylephrine, possibly by its combined α1- and β2-agonist properties.
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http://dx.doi.org/10.1097/SHK.0000000000001590DOI Listing
December 2020

Blood carboxyhemoglobin elimination curve, half-lifetime, and arterial-venous differences in acute phase of carbon monoxide poisoning in ovine smoke inhalation injury model.

Biochem Biophys Res Commun 2020 05 18;526(1):141-146. Epub 2020 Mar 18.

Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address:

Smoke inhalation injury (SII) affects more than 50,000 people annually causing carbon monoxide (CO) poisoning. Although the increased blood level of carboxyhemoglobin (CO-Hb) is frequently used to confirm the diagnosis of SII, knowledge of its elimination in the acute phase is still limited. The aim of this study is to determine CO-Hb elimination rates and their differences in arterial (aCO-Hb) and mixed-venous (vCO-Hb) blood following severe SII in a clinically relevant ovine model. Forty-three chronically instrumented female sheep were subjected to SII (12 breaths, 4 sets) through tracheostomy tube under anesthesia and analgesia. After the SII, sheep were awakened and placed on a mechanical ventilator (FiO = 1.0, tidal volume 12 mL/kg, and PEEP = 5cmHO) and monitored. Arterial and mixed-venous blood samples were withdrawn simultaneously for blood gas analysis at various time points to determine CO-HB half-lifetime and an elimination curve. The mean of highest aCO-Hb level during SII was 70.8 ± 13.9%. The aCO-Hb elimination curve showed an approximated exponential decay during the first 60 min. Per mixed linear regression model analysis, aCO-Hb significantly (p < 0.001) declined (4.3%/minute) with a decay constant lambda of 0.044. With this lambda, mean lifetime and half-lifetime of aCO-Hb were 22.7 and 15.7 min, respectively. The aCO-Hb was significantly lower compared to vCO-Hb at all-time points (0-180 min). To our knowledge, this is the first report describing CO-Hb elimination curve in the acute phase after severe SII in the clinically relevant ovine model. Our data shows that CO-Hb is decreasing in linear manner with supportive mechanical ventilation (0-60 min). The results may help to understand CO-Hb elimination curve in the acute phase and improvement of pre-hospital and initial clinical care in patients with CO poisoning.
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http://dx.doi.org/10.1016/j.bbrc.2020.03.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477924PMC
May 2020

Reply to "Predictors of Failing the American Board of Radiology Core Examination".

AJR Am J Roentgenol 2020 04;214(4):W73

University of Texas Medical Branch at Galveston, Galveston, TX

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http://dx.doi.org/10.2214/AJR.19.22417DOI Listing
April 2020

Effect of high-fat diet on peripheral blood mononuclear cells and adipose tissue in early stages of diet-induced weight gain.

Br J Nutr 2019 12;122(12):1359-1367

Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77550, USA.

Subcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.
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http://dx.doi.org/10.1017/S0007114519002472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908754PMC
December 2019

Predictors for Failing the American Board of Radiology Core Examination.

AJR Am J Roentgenol 2019 09 5;213(3):485-489. Epub 2019 Jun 5.

Department of Radiology, University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX 77555.

Since the American Board of Radiology (ABR) instituted its new board certification pathway, our residency program has had more residents fail the core examination than was typical with the prior pathway. We performed a single-center retrospective study to evaluate predictors of ABR core examination failure. Data regarding U.S. Medical Licensing Examination (USMLE) steps 1 and 2, ACR diagnostic radiology in-training examinations, the number of image interpretations, academic degree (doctor of medicine or doctor of osteopathy), status as an American or foreign medical graduate, and Alpha Omega Alpha national medical honor society status were gathered and evaluated through logistic regression and generalized additive logistic regression. Data were gathered for all residents who took the ABR core examination from 2013 to 2017. Six of 30 residents (20%) failed the ABR core examination on the first attempt. The ACR in-training examination scores for 1st- and 3rd-year residents were significantly related to ABR core examination failure ( = 0.027 and = 0.035, respectively), with significant nonlinearity ( = 0.037 and = 0.033, respectively). The suggested baseline percentile score was the 30th percentile for 1st-year residents and the 20th percentile for 3rd-year residents. USMLE step 1 and 2 scores were significantly related to ABR core examination failure ( = 0.041 and = 0.043, respectively), without significant nonlinearity ( = 0.35 and = 0.09, respectively). However, residents with scores of less than 220 on USMLE steps 1 and 2 seemed to be at risk. Low scores on USMLE steps 1 and 2 and 1st- and 3rd-year ACR in-training examinations were associated with ABR core examination failure. If validated more broadly, these cutoffs may serve as predictors of ABR core examination failure and may facilitate identification and remediation of at-risk residents.
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http://dx.doi.org/10.2214/AJR.18.21007DOI Listing
September 2019

Is insulin resistance the cause of fibromyalgia? A preliminary report.

PLoS One 2019 6;14(5):e0216079. Epub 2019 May 6.

Pain and Headache Center, Eagle River, Alaska, United States of America.

Fibromyalgia (FM) is one of the most frequent generalized pain disorders with poorly understood neurobiological mechanisms. This condition accounts for an enormous proportion of healthcare costs. Despite extensive research, the etiology of FM is unknown and thus, there is no disease modifying therapy available for this condition. We show that most (if not all) patients with FM belong to a distinct population that can be segregated from a control group by their glycated hemoglobin A1c (HbA1c) levels, a surrogate marker of insulin resistance (IR). This was demonstrated by analyzing the data after introducing an age stratification correction into a linear regression model. This strategy showed highly significant differences between FM patients and control subjects (p < 0.0001 and p = 0.0002, for two separate control populations, respectively). A subgroup of patients meeting criteria for pre-diabetes or diabetes (patients with HbA1c values of 5.7% or greater) who had undergone treatment with metformin showed dramatic improvements of their widespread myofascial pain, as shown by their scores using a pre and post-treatment numerical pain rating scale (NPRS) for evaluation. Although preliminary, these findings suggest a pathogenetic relationship between FM and IR, which may lead to a radical paradigm shift in the management of this disorder.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216079PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502334PMC
May 2019

Club Cell Protein, CC10, Attenuates Acute Respiratory Distress Syndrome Induced by Smoke Inhalation.

Shock 2020 03;53(3):317-326

University of Texas Medical Branch, Galveston, Texas.

Objectives: To evaluate the dose effects of Recombinant human Club cell 10-kDa protein (rhCC10) on lung function in a well-characterized ovine model of acute respiratory distress syndrome (ARDS) induced by smoke inhalation injury (SII); specifically, the potential of rhCC10 protein to control the inflammatory response and protect pulmonary tissue and function following SII.

Design: Randomized, controlled, prospective, and large animal translational studies.

Setting: University large animal intensive care unit.

Subjects: Thirty-six adult female sheep were surgically prepared and allocated into five groups (Sham (no SII), n = 6; 1 mg/kg/d CC10, n = 8; 3 mg/kg/d CC10, n = 7; 10 mg/kg/d CC10, n = 8; Control SII, n = 7).

Interventions: All groups except the sham group were subjected to SII with cooled cotton smoke. Then, the animals were placed on a ventilator, treated with 1, 3, and 10 mg/kg/d of intravenous rhCC10 or vehicle, divided evenly into two administrations per day every 12 h, fluid resuscitated, and monitored for 48 h in a conscious state.

Measurements And Main Results: The group treated with 10 mg/kg/d rhCC10 attenuated changes in the following variables: PaO2/FiO2 ratio, oxygenation index, and peak inspiratory pressure; neutrophil content in the airway and myeloperoxidase levels; obstruction of the large and small airways; systemic leakage of fluid and proteins, and pulmonary edema.

Conclusions: In this study, high-dose rhCC10 significantly attenuated ARDS progression and lung dysfunction and significantly reduced systemic extravasation of fluid and proteins, normalizing fluid balance. Based on these results, rhCC10 may be considered a novel therapeutic option for the treatment of SII-induced ARDS.
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http://dx.doi.org/10.1097/SHK.0000000000001365DOI Listing
March 2020

Cutaneous nontuberculous mycobacteria infections: A retrospective case series of 78 patients from the Texas Gulf Coast region.

J Am Acad Dermatol 2019 Sep 16;81(3):730-739. Epub 2019 Apr 16.

Department of Dermatology, University of Texas Medical Branch, Galveston, Texas.

Background: The incidence of cutaneous nontuberculous mycobacteria (NTM) infections is increasing. These infections are a diagnostic and therapeutic challenge.

Objective: We investigated the clinical features, diagnosis, and management of cutaneous NTM infections.

Methods: A retrospective case series studied 78 patients from a Gulf Coast tertiary referral center diagnosed with cutaneous NTM infection by culture or stain of a skin biopsy specimen.

Results: A history of trauma, procedure, or environmental exposure was common. The mean time between the initial evaluation and diagnosis was 12 weeks. Only 15% of acid-fast bacillus-positive cultures had a positive acid-fast bacillus smear, and only 43% of those accompanied by skin biopsy specimen had a positive Fite stain. Immunosuppressed patients were more likely to have a positive Fite stain. Treatment included surgery and multiple antibiotics. Immunosuppressed patients and Mycobacterium abscessus group infections were more likely to have persistent disease.

Limitations: M chelonae and M abscessus isolates were indistinguishable and therefore were reported together. Five cases were not confirmed by culture.

Conclusions: Even with clinical suspicion, the diagnosis of NTM infection can be difficult. Results of acid-fast bacillus smears and special stains are frequently negative. Antibiotic resistance is common. Multidrug treatment is often required, and surgical therapy may be needed.
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http://dx.doi.org/10.1016/j.jaad.2019.04.022DOI Listing
September 2019

Finding the Hidden (Statistical) Platform.

Crit Care Med 2019 03;47(3):480-483

Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX The Moody Project for Translational Traumatic Brain Injury Research, Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX.

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http://dx.doi.org/10.1097/CCM.0000000000003611DOI Listing
March 2019

Use of Isokinetic Dynamometry to Assess Muscle Function in Burned Patients is a Reliable Tool to Assist Progressive Resistance Exercise Prescription.

J Burn Care Res 2019 Jan 9. Epub 2019 Jan 9.

Department of Surgery, The University of Texas Medical Branch Galveston, TX.

Isokinetic dynamometry is used during exercise testing and rehabilitation to obtain a quantitative strength measurement on which progressive strength training programs can be based. This study assesses the test-retest reliability of isokinetic leg function in the knee flexors and extensors at 150 degrees/second in children and young adults with severe burns to be used for rehabilitation exercise program prescription. In 39 severely burned patients (49 ± 14% total body surface area burn [TBSA], mean ± SD; 34 ± 21% TBSA 3 rd degree; 14 ± 5 years, 153.3 ± 16.5 cm height; 53.8 ± 17.9 kg) knee flexion/extension isokinetic dynamometry at 150 degrees/second was performed on each patient's dominant leg in two sessions. The patient was acquainted with the test and performed 1 set of 10 repetitions at 150 degrees/second. A second session of 1 set of 10 repetitions at 150 degrees/second was performed within 24 hours of the first. Muscle function outcomes were knee flexion/extension peak torque, average peak torque, and average power. One-sample paired t-tests were performed for all muscle function outcomes; intraclass correlation coefficients and r2 values with session two as a function of session one were calculated. Sessions did not differ significantly in knee extension or flexion for any muscle function outcome or the hamstrings to quadriceps ratio. All intraclass correlation coefficients were >0.89 and r2 >0.79. Test-retest isokinetic dynamometry functional measurements in the knee flexors and extensors at 150 degrees/second are reliable in the burn population and may aid resistance rehabilitation program prescriptions.
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http://dx.doi.org/10.1093/jbcr/irz003DOI Listing
January 2019

Modulation of Peroxynitrite Reduces Norepinephrine Requirements in Ovine MRSA Septic Shock.

Shock 2019 11;52(5):e92-e99

Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas.

Vascular hypo-responsiveness to vasopressors during septic shock is a challenging problem. This study is to test the hypothesis that reactive nitrogen species (RNS), such as peroxynitrite, are major contributing factors to vascular hypo-responsiveness in septic shock. We hypothesized that adjunct therapy with peroxynitrite decomposition catalyst (PDC) would reduce norepinephrine requirements in sepsis resuscitation. Fourteen female Merino sheep were subjected to a "two-hit" injury (smoke inhalation and endobronchial instillation of live methicillin-resistant Staphylococcus aureus [1.6-2.5 × 10 CFUs]). The animals were randomly allocated to control: injured, fluid resuscitated, and titrated norepinephrine, n = 7; or PDC: injured, fluid resuscitated, titrated norepinephrine, and treated with PDC, n = 7. One-hour postinjury, an intravenous injection of PDC (0.1 mg/kg) was followed by a continuous infusion (0.04 mg/kg/h). Titration of norepinephrine started at 0.05 mcg/kg/min based on their mean arterial pressure. All animals were mechanically ventilated and monitored in the conscious state for 24 h. The mean arterial pressure was well maintained in the PDC with significantly less norepinephrine requirement from 7 to 23 h after injury compared with control. Total norepinephrine dose, the highest norepinephrine rate, and time on norepinephrine support were also significantly lower in PDC. Modified sheep organ failure assessment scores at 6 to 18 h postinjury were significantly lower in PDC compared with control. PDC improved survival rate at 24 h (71.4% vs. 28.6%). PDC treatment had no adverse effects. In conclusion, the modulation of RNS may be considered an effective adjunct therapy for septic shock, in the case of hypo-responsiveness to norepinephrine.
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http://dx.doi.org/10.1097/SHK.0000000000001297DOI Listing
November 2019

Quantification of muscle triglyceride synthesis rate requires an adjustment for total triglyceride content.

J Lipid Res 2018 10 21;59(10):2018-2024. Epub 2018 Aug 21.

Departments of Internal Medicine, University of Texas Medical Branch, Galveston, TX

Intramyocellular triglyceride (imTG) in skeletal muscle plays a significant role in metabolic health, and an infusion of [C]palmitate can be used to quantitate the in vivo fractional synthesis rate (FSR) and absolute synthesis rate (ASR) of imTGs. However, the extramyocellular TG (emTG) pool, unless precisely excised, contaminates the imTG pool, diluting the imTG-bound tracer enrichment and leading to underestimation of FSR. Because of the difficulty of excising the emTGs precisely, it would be advantageous to be able to calculate the imTG synthesis rate without dissecting the emTGs from each sample. Here, we tested the hypothesis that the ASR of total TGs (tTGs), a combination of imTGs and emTGs, calculated as "FSR × tTG pool," reasonably represents the imTG synthesis. Muscle lipid parameters were measured in nine healthy women at 90 and 170 min after the start of [C]palmitate infusion. While the measurements of tTG content, enrichment, and FSR did not correlate ( > 0.05), those of the tTG ASR were significantly correlated ( = 0.947, < 0.05). These results demonstrate that when imTGs and emTGs are pooled, the resulting underestimation of imTG FSR is balanced by the overestimation of the imTG content. We conclude that imTG metabolism is reflected by the measurement of the tTG ASR.
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http://dx.doi.org/10.1194/jlr.D082321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168308PMC
October 2018

Determinants of skeletal muscle protein turnover following severe burn trauma in children.

Clin Nutr 2019 06 4;38(3):1348-1354. Epub 2018 Jun 4.

Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA; Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas, USA.

Background & Aims: Burns remain the fifth cause of non-fatal pediatric injuries globally, with muscle cachexia being a hallmark of the stress response to burns. Burn-induced muscle wasting is associated with morbidity, yet the determinants of muscle protein catabolism in response to burn trauma remains unclear. Our objective was to determine the effect of patient and injury characteristics on muscle protein kinetics in burn patients.

Methods: This retrospective, observational study was performed using protein kinetic data from pediatric patients who had severe burns (>30% of the total body surface area burned) and underwent cross-limb stable isotope infusions between 1999 and 2008 as part of prospective clinical trials. Mixed multiple regression models were used to assess associations between patient/injury characteristics and muscle protein fractional synthesis rate (FSR), net balance (NB), and rates of phenylalanine appearance (Ra; index of protein breakdown) and disappearance (Rd; index of protein synthesis) across the leg.

Results: A total of 268 patients who underwent 499 studies were analyzed. Increasing time post injury was associated with greater FSR (p < 0.001) and NB (p = 0.01). Males were more catabolic than females (as indicated by lower NB, p = 0.04 and greater Ra, p = 0.008), a consequence of higher protein breakdown rather than lower synthesis. Increasing burn size was associated with higher protein synthesis rate (as indicated by higher FSR, p = 0.019) and higher protein breakdown rates (as indicated by greater Ra, p = 0.001). FSR was negatively associated with age (p < 0.001).

Conclusions: Data from this large patient cohort show that injury severity, sex, and time post injury influence skeletal muscle wasting in burned children. These findings suggest that individual patient characteristics should be considered when devising therapies to improve the acute care and rehabilitation of burn survivors.
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http://dx.doi.org/10.1016/j.clnu.2018.05.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279601PMC
June 2019

The Safety and Efficacy of Propranolol in Reducing the Hypermetabolic Response in the Pediatric Burn Population.

J Burn Care Res 2018 10;39(6):963-969

Shriners Hospitals for Children and Department of Psychiatry, University of Texas Medical Branch, Galveston, Texas.

Pediatric burn patients often have hypertension and tachycardia for several years post-injury. Propranolol has shown to be effective in treating the hypermetabolic state secondary to a major burn injury. This study was conducted to document a safe and effective dosing regimen for three different age groups. One hundred four burn-injured children with a 30% to 92% total body surface area burn were treated for 1 to 2 years with propranolol in the outpatient setting. Guardians of the patients were instructed on how to take and monitor the systolic blood pressure and heart rate, and document their vital signs several times a day. The documentation was reviewed with the guardian and patient, and based on age-specific vital sign parameters, propranolol dosing adjustment was done to measure at least 15% to 20% reduction in admission heart rate. Mean doses for the age groups were as follows: 0 to 3 years 5.2 ± 2.8 mg/kg/day, 4 to 10 years 4.2 ± 1.8 mg/kg/day, and 11 to 18 years 2.9 ± 1.4 mg/kg/day. The propranolol dose decreased as time post-burn increased. On selected patients, propranolol was stopped due to changes in the heart rate, but at all times, it was safe and effective. No adverse effects were noted. The dosing regimen was not affected by burn size or gender. Propranolol can be safely stopped abruptly with no rebound hypertension. Individuals older than 10 years required a lower dose per kilogram following the burn injury than prepubertal burn survivors. Propranolol proved to be both safe and effective in the management of cardiovascular changes occurring in the hypermetabolic state.
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http://dx.doi.org/10.1093/jbcr/iry014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198736PMC
October 2018

Discharge Patterns for Ischemic and Hemorrhagic Stroke Patients Going From Acute Care Hospitals to Inpatient and Skilled Nursing Rehabilitation.

Am J Phys Med Rehabil 2018 09;97(9):636-645

From the Department Occupational Therapy, University of Texas Medical Branch, Galveston, Texas (IH, TAR); Division of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas (AK, KJO); Preventive Medicine & Community Health, University of Texas Medical Branch, Galveston, Texas (WC, Y-FK, CRA); Department of Clinical Research and Leadership, George Washington University, Washington, District of Columbia (TM); and Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas (JSG).

Objective: The aim of the study was to explore variation in acute care use of inpatient rehabilitation facilities and skilled nursing facilities rehabilitation after ischemic and hemorrhagic stroke.

Design: A secondary analysis of Medicare claims data linked to inpatient rehabilitation facilities and skilled nursing facilities assessment files (2013-2014) was performed.

Results: The sample included 122,084 stroke patients discharged to inpatient or skilled nursing facilities from 3677 acute hospitals. Of the acute hospitals, 3649 discharged patients with an ischemic stroke (range = 1-402 patients/hospital, median = 15) compared with 1832 acute hospitals that discharged patients with hemorrhagic events (range = 1-73 patients/hospital, median = 4). The intraclass correlation coefficient examined variation in discharge settings attributed to acute hospitals (ischemic intraclass correlation coefficient = 0.318, hemorrhagic intraclass correlation coefficient = 0.176). Patients older than 85 yrs and those with greater numbers of co-morbid conditions were more likely to discharge to skilled nursing facilities. Comparison of self-care and mobility across stroke type suggests that patients with ischemic stroke have higher functional abilities at admission.

Conclusions: This study suggests demographic and clinical differences among stroke patients admitted for postacute rehabilitation at inpatient rehabilitation facilities and skilled nursing facilities settings. Furthermore, examination of variation in ischemic and hemorrhagic stroke discharges suggests acute facility-level differences and indicates a need for careful consideration of patient and facility factors when comparing the effectiveness of inpatient rehabilitation facilities and skilled nursing facilities rehabilitation.
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http://dx.doi.org/10.1097/PHM.0000000000000932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095808PMC
September 2018

Poverty, population density, and the epidemiology of burns in young children from Mexico treated at a U.S. pediatric burn facility.

Burns 2018 08 7;44(5):1269-1278. Epub 2018 Mar 7.

Shriners Hospitals for Children in Galveston Texas, 77550, USA; Department of Surgery at the University of Texas Medical Branch, Galveston, TX 77555, USA.

Introduction: Children 5 and younger are at risk for sustaining serious burn injuries. The causes of burns vary depending on demographic, cultural and socioeconomic variables. At this pediatric burn center we provided medical care to children from Mexico with severe injuries. The purpose of this study was to understand the impact of demographic distribution and modifiable risk factors of burns in young children to help guide prevention.

Methods: A retrospective chart review was performed with children 5 and younger from Mexico who were injured from 2000-2013. The medical records of 447 acute patients were reviewed. Frequency counts and percentages were used to identify geographic distribution and calculate incidence of burns. Microsoft Powermap software was used to create a geographical map of Mexico based on types of burns. A binomial logistic regression was used to model the incidence of flame burns as opposed to scald burns in each state with relation to population density and poverty percentage. In all statistical tests, alpha=0.05 for a 95% level of confidence.

Results: Burns were primarily caused by flame and scald injuries. Admissions from flame injuries were mainly from explosions of propane tanks and gas lines and house fires. Flame injuries were predominantly from the states of Jalisco, Chihuahua, and Distrito Federal. Scalds were attributed to falling in large containers of hot water or food on the ground, and spills of hot liquids. Scald injuries were largely from the states of Oaxaca, Distrito Federal, and Hidalgo. The odds of a patient having flame burns were significantly associated with poverty percentage (p<0.0001) and population density (p=0.0085). Increasing levels of poverty led to decrease in odds of a flame burn, but an increase in the odds of scald burns. Similarly, we found that increasing population density led to a decrease in the odds of a flame burn, but an increase in the odds of a scald burn.

Conclusions: Burns in young children from Mexico who received medical care at this pediatric burn center were attributed to flame and scalds. Potential demographic associations have been identified. Different states in Mexico have diverse cultural and socioeconomic variables that may influence the etiology of burns in young children and this information may help efficiently tailor burn prevention campaigns for burn prevention efforts in each region.

Applicability Of Research To Practice: This information will be used to develop and help modify existing prevention campaigns.
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http://dx.doi.org/10.1016/j.burns.2018.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453533PMC
August 2018

Adapting the Elixhauser comorbidity index for cancer patients.

Cancer 2018 05 1;124(9):2018-2025. Epub 2018 Feb 1.

Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas.

Background: This study was designed to adapt the Elixhauser comorbidity index for 4 cancer-specific populations (breast, prostate, lung, and colorectal) and compare 3 versions of the Elixhauser comorbidity score (individual comorbidities, summary comorbidity score, and cancer-specific summary comorbidity score) with 3 versions of the Charlson comorbidity score for predicting 2-year survival with 4 types of cancer.

Methods: This cohort study used Texas Cancer Registry-linked Medicare data from 2005 to 2011 for older patients diagnosed with breast (n = 19,082), prostate (n = 23,044), lung (n = 26,047), or colorectal cancer (n = 16,693). For each cancer cohort, the data were split into training and validation cohorts. In the training cohort, competing risk regression was used to model the association of Elixhauser comorbidities with 2-year noncancer mortality, and cancer-specific weights were derived for each comorbidity. In the validation cohort, competing risk regression was used to compare 3 versions of the Elixhauser comorbidity score with 3 versions of the Charlson comorbidity score. Model performance was evaluated with c statistics.

Results: The 2-year noncancer mortality rates were 14.5% (lung cancer), 11.5% (colorectal cancer), 5.7% (breast cancer), and 4.1% (prostate cancer). Cancer-specific Elixhauser comorbidity scores (c = 0.773 for breast cancer, c = 0.772 for prostate cancer, c = 0.579 for lung cancer, and c = 0.680 for colorectal cancer) performed slightly better than cancer-specific Charlson comorbidity scores (ie, the National Cancer Institute combined index; c = 0.762 for breast cancer, c = 0.767 for prostate cancer, c = 0.578 for lung cancer, and c = 0.674 for colorectal cancer). Individual Elixhauser comorbidities performed best (c = 0.779 for breast cancer, c = 0.783 for prostate cancer, c = 0.587 for lung cancer, and c = 0.687 for colorectal cancer).

Conclusions: The cancer-specific Elixhauser comorbidity score performed as well as or slightly better than the cancer-specific Charlson comorbidity score in predicting 2-year survival. If the sample size permits, using individual Elixhauser comorbidities may be the best way to control for confounding in cancer outcomes research. Cancer 2018;124:2018-25. © 2018 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.31269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910176PMC
May 2018

Effects of Community-Based Exercise in Adults With Severe Burns: A Randomized Controlled Trial.

Arch Phys Med Rehabil 2020 01 31;101(1S):S36-S41. Epub 2018 Jan 31.

Department of Surgery, University of Texas Medical Branch, Galveston, TX; Shriners Hospitals for Children, Galveston, TX. Electronic address:

Objective: To investigate the efficacy of community-based exercise programs in the rehabilitation of adult patients with burns compared with standard of care (SOC).

Design: Randomized controlled trial, with 2:1 randomization.

Setting: Assessments were performed in a hospital setting. The intervention was performed in a community setting.

Participants: Adult patients (N=45) with ≥30% total body surface area burns were randomized to participate in a community-based exercise program (n=31) or SOC (n=14). Patient sampling was consecutive and referred.

Interventions: The community-based exercise program consisted of 12 weeks of exercise with a community-based trainer after hospital discharge. The SOC group did not receive exercise training.

Main Outcome Measures: Change in lean body mass index, peak torque, and peak oxygen consumption from discharge to 12 weeks postdischarge, presented as mean ± SE.

Results: The community-based exercise program group showed a significant increase in peak oxygen consumption compared with SOC (community-based exercise program: Δ=7.723±1.522mL/kg/min, P=.0006; SOC: Δ=2.200±1.150mL/kg/min, P=.0765; community-based exercise program vs SOC, P=.0236). The community-based exercise program group exhibited a significant within group increase in lean body mass index (Δ=1.107±0.431kg/m, P=.0003; SOC: Δ=1.323±0.873kg/m, P=.2808). Both groups showed significant within-group increases in peak torque (community-based exercise program: Δ=35.645±7.566Nm, P=.0003; SOC: Δ=34.717±11.029Nm, P=.0082). No significant differences were noted between the 2 groups for lean body mass index or peak torque.

Conclusions: Patients who participate in a community-based exercise program show significant improvements in cardiopulmonary fitness compared with SOC, supporting the use of a community-based exercise program as an alternative therapy to SOC in adults with severe burns.
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http://dx.doi.org/10.1016/j.apmr.2017.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092257PMC
January 2020

One-Year Comparison of a Community-Based Exercise Program Versus a Day Hospital-Based Exercise Program on Quality of Life and Mental Health in Severely Burned Children.

Arch Phys Med Rehabil 2020 01 26;101(1S):S26-S35. Epub 2017 Nov 26.

Department of Psychology, University of Texas Medical Branch/Shriners Hospitals for Children, Galveston, TX.

Objective: To compare the effects of long-term psychosocial functioning and mental health of a "day hospital"-based exercise program (DAYEX) versus a community-based exercise program (COMBEX).

Design: A prospective design that consisted of 2 groups (DAYEX and COMBEX).

Setting: A children's hospital specialized in burn care.

Participants: Patients (N=18; DAYEX [n=9], COMBEX [n=9]) were assessed at intensive care unit discharge and up to 1 year postburn.

Interventions: The Child Health Questionnaires (CHQ-Child Form [CHQ-CF87] and CHQ-Parent Form [CHQ-PF28]) were used to assess changes in quality of life from discharge to 1 year postburn.

Main Outcome Measures: CHQ-PF28 and CHQ-CF87.

Results: Demographic characteristics and total body surface area burned were similar in both groups. Length of hospital stay was significant in the COMBEX group. CHQ-CF87 and CHQ-PF28 documented significant improvements in both groups between discharge and 1 year. Significance was evident in Physical Functioning, Bodily Pain, Self-Esteem, Change in Health, and Family Activities. CHQ-CF87 showed improvement in Family Cohesion in COMBEX more than DAYEX. CHQ-PF28 showed improvement in Role/Social Limitations-Emotional, Bodily Pain, and Family Activities in COMBEX more than DAYEX.

Conclusions: The proposed COMBEX program is feasible and beneficial physically, psychosocially, and mentally. The results show some improvements in the COMBEX group in optimizing function and health in severely burned children. The COMBEX group performed at least as well as the DAYEX group. Larger-scale studies are needed to validate current findings.
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http://dx.doi.org/10.1016/j.apmr.2017.10.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970960PMC
January 2020

Characterization of Adipose-Derived Stem Cells Following Burn Injury.

Stem Cell Rev Rep 2017 Dec;13(6):781-792

Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.

Severe burns induce a prolonged inflammatory response in subcutaneous adipose tissue that modulates signaling in adipose-derived stem cells (ASCs), which hold potential for healing burn wounds or generating skin substitutes. Using a 60% rat scald burn model, we conducted a series of experiments to determine which cells isolated from the adipose tissue produced inflammatory mediators and how these changes affect ASC fate and function. The stromal vascular fraction (SVF), adipocytes, and ASCs were isolated from adipose tissue at varying times up to 4 weeks postburn and from non-injured controls. Endpoints included inflammatory marker expression, expression of ASC-specific cell-surface markers, DNA damage, differentiation potential, and proliferation. Inflammatory marker expression was induced in adipocytes and the SVF at 24 and 48 h postburn; expression of inflammatory marker mRNA transcripts and protein returned to normal in the SVF isolated 1 week postburn. In enriched ASCs, burns did not alter cell-surface expression of stem cell markers, markers of inflammation, differentiation potential, or proliferative ability. These results suggest that adipocytes and the SVF produce large quantities of inflammatory mediators, but that ASCs do not, after burns and that ASCs are unaffected by burn injury or culturing procedures.. They also suggest that cells isolated over 48 h after injury are best for cell culture or tissue engineering purposes.
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http://dx.doi.org/10.1007/s12015-017-9721-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730636PMC
December 2017

Propranolol kinetics in plasma from severely burned adults.

Burns 2017 Sep 20;43(6):1168-1174. Epub 2017 Jun 20.

Department of Surgery, University of Texas Medical Branch, Galveston, TX, United States; Institute for Translational Sciences and Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, TX, United States; Shriners Hospitals for Children(®) - Galveston, Galveston, TX, United States. Electronic address:

Objectives: The aim of this study was to determine the appropriate propranolol dosing strategy for reducing heart rate in severely burned adults.

Methods: A total of 26 patients (≥18 years) with burns covering ≥30% of the total body surface area were included in this IRB-approved study. Plasma propranolol concentrations were determined in a placebo group (n=10) or following one of three dosing strategies: Q6 (n=4), Q8 (n=6), and Q24 (n=6). Blood was collected just before dosing and at regular intervals over two dosing periods with corresponding heart rate and blood pressure recordings. Statistical significance was determined by one-way ANOVA followed by the appropriate post-hoc test.

Results: Heart rate was 86±2 bpm for Q6, 93±3 bpm for Q8, and 90±4 bpm for Q24. The Q8 group had a significantly higher heart rate than the Q6 group (p=0.0001). Plasma propranolol concentrations were significantly higher in the Q6 dosing strategy than in the Q8 dosing strategy (p=0.02).

Conclusions: Heart rate can be decreased to a similar degree with Q6 and Q24 dosing strategies, with the Q8 dosing strategy being less effective. Q6 dosing is recommended to maintain reduced heart rate throughout dosing periods.
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http://dx.doi.org/10.1016/j.burns.2016.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173765PMC
September 2017