Lung Protective Mechanical Ventilation (MV) of critically ill adults and children is lifesaving but it may decrease diaphragm contraction and promote Ventilator Induced Diaphragm Dysfunction (VIDD). ...An ideal MV strategy would balance lung and diaphragm protection. Building off a Phase I pilot study, we are conducting a Phase II controlled clinical trial that seeks to understand the evolution of VIDD in critically ill children and test whether a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)) can balance lung and diaphragm protective ventilation to reduce time on MV. REDvent systematically adjusts PEEP, FiO2, inspiratory pressure, tidal volume and rate, and uses real-time measures from esophageal manometry to target normal levels of patient effort of breathing. This trial targets 276 children with pulmonary parenchymal disease. Patients are randomized to REDvent vs. usual care for the acute phase of MV (intubation to first Spontaneous Breathing Trial (SBT)). Patients in either group who fail their first SBT will be randomized to REDvent vs usual care for weaning phase management (interval from first SBT to passing SBT). The primary clinical outcome is length of weaning, with several mechanistic outcomes. Upon completion, this study will provide important information on the pathogenesis and timing of VIDD during MV in children and whether this computerized protocol targeting lung and diaphragm protection can lead to improvement in intermediate clinical outcomes. This will form the basis for a larger, Phase III multi-center study, powered for key clinical outcomes such as 28-day ventilator free days.
Clinical Trials Registration: NCT03266016
Background. Stroke patients with mild-moderate upper extremity motor impairments and minimal sensory and cognitive deficits provide a useful model to study recovery and improve rehabilitation. ...Laboratory-based investigators use lesioning techniques for similar goals. Objective. To determine whether stroke lesions in an upper extremity rehabilitation trial cohort match lesions from the preclinical stroke recovery models used to drive translational research. Methods. Clinical neuroimages from 297 participants enrolled in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study were reviewed. Images were characterized based on lesion type (ischemic or hemorrhagic), volume, vascular territory, depth (cortical gray matter, cortical white matter, subcortical), old strokes, and leukoaraiosis. Lesions were compared with those of preclinical stroke models commonly used to study upper limb recovery. Results. Among the ischemic stroke participants, median infarct volume was 1.8 mL, with most lesions confined to subcortical structures (61%) including the anterior choroidal artery territory (30%) and the pons (23%). Of ICARE participants, <1% had lesions resembling proximal middle cerebral artery or surface vessel occlusion models. Preclinical models of subcortical white matter injury best resembled the ICARE population (33%). Intracranial hemorrhage participants had small (median 12.5 mL) lesions that best matched the capsular hematoma preclinical model. Conclusions. ICARE subjects are not representative of all stroke patients, but they represent a clinically and scientifically important subgroup. Compared with lesions in general stroke populations and widely studied animal models of recovery, ICARE participants had smaller, more subcortically based strokes. Improved preclinical-clinical translational efforts may require better alignment of lesions between preclinical and human stroke recovery models.
Research imaging costs limit lesion-based analyses in already expensive large stroke rehabilitation trials. Despite the belief that lesion characteristics influence recovery and treatment response, ...prior studies have not sufficiently addressed whether lesion features are an important consideration in motor rehabilitation trial design.
Using clinically-obtained neuroimaging, evaluate how lesion characteristics relate to upper extremity (UE) recovery and response to therapy in a large UE rehabilitation trial.
We reviewed lesions from 297 participants with mild-moderate motor impairment in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study and their association with motor recovery, measured by the UE Fugl-Meyer (UE-FM). Significant lesion features identified on correlational and bivariate analysis were further analyzed for associations with recovery and therapy response using longitudinal mixed models.
Prior radiographic stroke was associated with less recovery on UE-FM in participants with motor impairment from subsequent subcortical stroke (-5.8 points) and in the overall sample (-3.6 points), but not in participants with cortical or mixed lesions. Lesion volume was also associated with less recovery, particularly after subcortical stroke. Every decade increase in age was associated with 1 less point of recovery on UE-FM. Response to specific treatment regimens varied based on lesion characteristics. Subcortical stroke patients experienced slightly less recovery with higher doses of upper extremity task-oriented training. Participants with cortical or mixed lesions experienced more recovery with higher doses of usual and customary therapy. Other imaging features (leukoaraiosis, ischemic vs. hemorrhagic stroke) were not significant.
ICARE clinical imaging revealed information useful for UE motor trial design: stratification of persons with and without prior radiographic stroke may be required in participants with subcortical stroke, the majority of motor rehabilitation trial participants. Most of the prior radiographic strokes were small and cortically-based, suggesting even minor prior brain injury remote to the acute stroke lesion may limit spontaneous and therapy-related recovery. Lesion location may be associated with response to different therapy regimens, but the effects are variable and of unclear significance.
Background:
There has been a surge in high-level studies investigating platelet-rich plasma (PRP) for tendon and ligament injuries. A number of meta-analyses have been published, but few studies have ...focused exclusively on tendon and ligament injuries.
Purpose:
To perform a meta-analysis assessing the ability of PRP to reduce pain in patients with tendon and ligament injuries.
Study Design:
Systematic review and meta-analysis.
Methods:
This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of the literature was carried out in April 2017 using electronic databases PubMed, MEDLINE, and the Cochrane Library. Only level 1 studies were included. Platelet and leukocyte count, injection volume, kit used, participant age/sex, comparator, and activating agent used were recorded. The short-term and long-term efficacy of PRP was assessed using the visual analog scale (VAS) to measure pain intensity. Injury subgroups (rotator cuff, tendinopathy, anterior cruciate ligament, and lateral epicondylitis) were evaluated. Funnel plots and the Egger test were used to screen for publication bias, and sensitivity analysis was performed to evaluate the effect of potential outliers by removing studies one at a time.
Results:
Thirty-seven articles were included in this review, 21 (1031 participants) of which could be included in the quantitative analysis. The majority of studies published investigated rotator cuff injuries (38.1%) or lateral epicondylitis (38.1%). Seventeen studies (844 participants) reported short-term VAS data, and 14 studies (771 participants) reported long-term VAS data. Overall, long-term follow-up results showed significantly less pain in the PRP group compared with the control group (weighted mean difference WMD, –0.84; 95% CI, –1.23 to –0.44; P < .01). Patients treated with PRP for rotator cuff injuries (WMD, –0.53; 95% CI, –0.98 to –0.09; P = .02) and lateral epicondylitis (WMD, –1.39; 95% CI, –2.49 to –0.29; P = .01) reported significantly less pain in the long term. Substantial heterogeneity was reported at baseline (I2 = 72.0%; P < .01), short-term follow-up (I2 = 72.5%; P < .01), long-term follow-up (I2 = 76.1%; P < .01), and overall (I2 = 75.8%; P < .01). The funnel plot appeared to be asymmetric, with some missingness at the lower right portion of the plot suggesting possible publication bias.
Conclusion:
This review shows that PRP may reduce pain associated with lateral epicondylitis and rotator cuff injuries.
Background:
Many clinical trials have investigated the use of platelet-rich plasma (PRP) to treat rotator cuff–related abnormalities. Several meta-analyses have been published, but none have focused ...exclusively on level 1 randomized controlled trials.
Purpose:
To assess the efficacy of PRP for rotator cuff–related abnormalities and evaluate how specific tendon involvement, the inclusion of leukocytes, and the use of gel/nongel formulations affect pain and functional outcomes.
Study Design:
Systematic review and meta-analysis.
Methods:
The literature was screened following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Baseline, short-term, and long-term data were extracted for the Constant score, University of California, Los Angeles (UCLA) score, visual analog scale (VAS) for pain, retear rate, Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons (ASES) score. The 100-point modified Coleman Methodology Score (CMS) was used to assess methodological quality. Funnel plots and the Egger test were used to screen for publication bias, and sensitivity analysis was performed to evaluate the effect of potential outliers.
Results:
A total of 18 level 1 studies were included in this review, 17 (1116 patients) of which could be included in quantitative analysis. The mean modified CMS was 79.4 ± 10.39. The Constant scores of patients who received PRP were significantly better short term (weighted mean difference WMD, 2.89 95% CI, 0.89-4.90; P < .01) and long term (WMD, 2.66 95% CI, 1.13-4.19; P < .01). The VAS scores were significantly improved short term (WMD, –0.45 95% CI, –0.75 to −0.15; P < .01). Sugaya grade IV and V retears in PRP-treated patients were significantly reduced long term (odds ratio OR, 0.34 95% CI, 0.20-0.57; P < .01). In PRP-treated patients with multiple tendons torn, there were reduced odds of retears (OR, 0.28 95% CI, 0.13-0.60; P < .01). Patients who received leukocyte-rich PRP had significantly better Constant scores compared with the leukocyte-poor PRP group, but there was no difference in VAS scores. Patients receiving PRP gel reported higher Constant scores compared with the controls, whereas those receiving nongel PRP treatments did not, although there was no difference in VAS scores. Long-term odds of retears were decreased, regardless of leukocyte content (leukocyte-poor PRP: OR, 0.36 95% CI, 0.16-0.82; leukocyte-rich PRP: OR, 0.32 95% CI, 0.16-0.65; all P < .05) or usage of gel (nongel: OR, 0.42 95% CI, 0.23-0.76; gel: OR, 0.17 95% CI, 0.05-0.51; all P < .01).
Conclusion:
Long-term retear rates were significantly decreased in patients with rotator cuff–related abnormalities who received PRP. Significant improvements in PRP-treated patients were noted for multiple functional outcomes, but none reached their respective minimal clinically important differences. Overall, our results suggest that PRP may positively affect clinical outcomes, but limited data, study heterogeneity, and poor methodological quality hinder firm conclusions.
Abstract
Introduction: Esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal cancers worldwide but is less common in the developed world. Our aim was to report patient and tumor ...characteristics of individuals diagnosed with ESCC within the underserved Los Angeles County population. Methods: Review of the hospital pathology database identified 65 cases of patients ages 18-80 with a pathologic diagnosis of ESCC from 2003-2015. A retrospective chart review of electronic health records was conducted excluding patients of unknown ethnicity leaving 61 patients. Patients were characterized by gender, age, alcohol and tobacco use, and family history. Endoscopy and pathology reports were reviewed to confirm tumor location, length, and pathological staging. Frequency counts and percentages were reported for categorical characteristics. A chi-square test or Fisher’s Exact test was performed to assess if characteristic variables differed by ethnicity. Results: Patients identified with ESCC in our cohort were predominantly Hispanic (59%, n=36) and 41% were non-Hispanic (n=10 Asian, n=10 African Americans, and n=5 Caucasian). ESCC was more commonly diagnosed in males vs. females in Hispanics and non-Hispanics (83.3% and 80% vs 16.7% and 20%, p=0.75). Age of diagnosis was between the ages of 18-60 years in nearly 56% and greater than 60 years in 44% of Hispanics and non-Hispanics (p=0.97). Most Hispanics and non-Hispanics had exposure to alcohol (74.1% and 85%, p=0.48) or tobacco (53.9% and 68.2%, p=.31). Most Hispanic and non-Hispanics did not have a family history of cancer (72% and 80%, p=0.73). Tumor location was most often proximal in Hispanic and non-Hispanics (66.7% and 83.3%, p=0.16) and of similar length (p=0.29). Most tumors in both Hispanic and non-Hispanic patients were moderately/poorly differentiated (82.9% and 91.3%, p=0.46). Hispanics were less likely to present with metastatic ESCC as compared to non-Hispanic patients (42.3% vs. 75%, p=0.03). Conclusion: ESCC in both groups within the Los Angeles County population were diagnosed most often in the proximal esophagus of males with history of exposure to alcohol and/or tobacco. Despite similar patient and tumor characteristics, ESCC in Hispanics was less often metastatic at the time of diagnosis compared to non-Hispanics. Despite the small numbers, our study is one of the few to include a large cohort of Hispanics and support further investigation of factors in different ethnicities that may be protective against advanced disease.
Citation Format: Divya Ayyala, Caron Park, Yanling Ma, Gregory Idos, Anisa Shaker. Retrospective study of patients with esophageal squamous cell carcinoma in an urban safety net county hospital abstract. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D103.
INTRODUCTION:
Esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal cancers worldwide but is less common in the developed world. Our aim was to report patient and tumor ...characteristics of individuals diagnosed with ESCC within the underserved Los Angeles County population.
METHODS:
Review of the hospital pathology database identified 65 cases of patients ages 18-80 with a pathologic diagnosis of ESCC from 2003-2015. A retrospective chart review of electronic health records was conducted excluding patients of unknown ethnicity leaving 61 patients. Patients were characterized by gender, age, alcohol and tobacco use, and family history. Endoscopy and pathology reports were reviewed to confirm tumor location, length, and pathological staging. Frequency counts and percentages were reported for categorical characteristics. A chi-square test or Fisher’s Exact test was performed to assess if characteristic variables differed by ethnicity.
RESULTS:
Patients identified with ESCC in our cohort were predominantly Hispanic (59%, n = 36) and 41% were non-Hispanic (n = 10 Asian, n = 10 African Americans, and n = 5 Caucasian). ESCC was more commonly diagnosed in males vs. females in Hispanics and non-Hispanics (83.3% and 80% vs 16.7% and 20%,
P
= 0.75). Age of diagnosis was between the ages of 18-60 years in nearly 56% and greater than 60 years in 44% of Hispanics and non-Hispanics (
P
= 0.97). Most Hispanics and non-Hispanics had exposure to alcohol (74.1% and 85%,
P
= 0.48) or tobacco (53.9% and 68.2%,
P
= .31). Most Hispanic and non-Hispanics did not have a family history of cancer (72% and 80%,
P
= 0.73). Tumor location was most often proximal in Hispanic and non-Hispanics (66.7% and 83.3%,
P
= 0.16) and of similar length (
P
= 0.29). Most tumors in both Hispanic and non-Hispanic patients were moderately/poorly differentiated (82.9% and 91.3%,
P
= 0.46). Hispanics were less likely to present with metastatic ESCC as compared to non-Hispanic patients (42.3% vs. 75%,
P
= 0.03).
CONCLUSION:
ESCC in both groups within the Los Angeles County population were diagnosed most often in the proximal esophagus of males with history of exposure to alcohol and/or tobacco. Despite similar patient and tumor characteristics, ESCC in Hispanics was less often metastatic at the time of diagnosis compared to non-Hispanics. Despite the small numbers, our study is one of the few to include a large cohort of Hispanics and support further investigation of factors in different ethnicities that may be protective against advanced disease.
To assess the efficacy of platelet-rich plasma (PRP) for lateral epicondylitis and evaluate its impact on pain and functional outcomes.
This study followed Preferred Reporting Items and Systematic ...Reviews and Meta-Analyses guidelines. A comprehensive literature search was conducted in September 2019 and repeated in April 2020 using electronic databases PubMed, MEDLINE, and the Cochrane Library. Baseline and 3-, 6-, and 12-month data were extracted for visual analog scale (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH), and modified Mayo Clinic performance index for the elbow (MAYO) scores. Only level 1 studies with patients who had not undergone surgery were included. Outcomes data, study design, demographic variables, PRP formulation, and comparator treatments were recorded. Statistical analyses of pooled weighted mean differences (WMDs) were performed and compared with estimated minimal clinically important difference (MCID) values. The Coleman Methodology Score (CMS) was used to assess methodological quality, and the Cochrane risk-of-bias assessment was performed.
This review included 16 level I studies, 9 of which (581 total patients, 281 receiving single injections of PRP) were quantitatively analyzed. The average age was 41.5 years, 56.8% of patients were female, and mean follow-up was 7.5 months. The mean CMS was 78.94 ± 12.74 (range 59 to 97), and 5 of 16 studies were at low risk for bias. Patients who received PRP had significantly improved VAS scores at 3 months (WMD –0.85; 95% confidence interval CI –1.03, –0.66; P < .01) and 6 months (WMD –0.74; 95% CI –0.98, –0.50; P < .01) compared with those who received autologous whole blood, though MAYO scores were statistically equivalent. Comparing PRP to corticosteroids, VAS and DASH scores were not significantly different at 3 months, although PRP was superior at 6 months for VAS (WMD –1.70; 95% CI –2.65, –0.75; P < .01) and DASH (WMD –6.23; 95% CI –10.78, –1.69; P < .01). Most differences in VAS and DASH scores exceeded the 5% absolute difference estimate for their respective MCIDs but fell short of the 10% estimate.
Considering the small number of comparable studies, lack of quantification of specific PRP content, considerable heterogeneity between randomized control trials, and most effect sizes being equivocal within the framework of 2 estimated MCID values, the authors can neither scientifically support nor discourage the usage of PRP for lateral epicondylitis despite finding statistically significant improvements in pain and functional outcomes.
I, prognostic.
The classic “trimodal” distribution of death has been described in adult patients, but the timing of mortality in injured children is not well understood. The purpose of this study was to define the ...temporal distribution of mortality in pediatric trauma patients.
A retrospective cohort of patients with mortality from the National Trauma Data Bank (2007–2014) was analyzed. Categorical comparison of ‘dead on arrival’, ‘death in the emergency department’, and early (≤24h) or late (>24h) inpatient death was performed. Secondary analyses included mortality by pediatric age, predictors of early mortality, and late complication rates.
Children (N=5463 deaths) had earlier temporal distribution of death compared to adults (n=104,225 deaths), with 51% of children dead on arrival or in ED compared to 44% of adults (p<0.001). For patients surviving ED resuscitation, children and adolescents had a shorter median time to death than adults (1.2 d and 0.8 days versus 1.6 days, p<0.001). Older age, penetrating mechanism, bradycardia, hypotension, tube thoracostomy, and thoracotomy were associated with early mortality in children.
Injured children have higher incidence of early mortality compared to adults. This suggests that injury prevention efforts and strategies for improving early resuscitation have potential to improve mortality after pediatric injury.
Level III: Retrospective cohort study.
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