Fractional CO2 Laser for Burn Scars: A Comparison of Patient Reported Outcomes Between Those With and Without Laser Treatment.

Burn reconstruction outcomes are an area of growing investigation. Although there is evidence of measured physical improvements in scar characteristics after laser treatment, there is little information on patient reported outcomes. The purpose of this study is to compare patient reported outcomes between burn survivors with and without laser treatment. The study included participants in the Burn Model Systems National Database at a single center; participants that received outpatient laser treatment for burn scars were compared to a matched group of burn survivors that did not receive laser. The following outcomes were examined: Satisfaction With Life Scale, Mental and Physical Component Summary of the Veterans Rand Survey, and the PROMIS Pain Intensity Scale. Regression analyses examined the associations between laser treatment and each outcome at 12 and 24 months. The study population included 287 adult burn survivors (65 laser group, 222 control group). The significant differences found between the two groups included: burn size (laser: 14.9, 13.5 SD, control: 8.9, 11.1 SD; p<0.001), insurance type (p=0.036), inhalation injury (laser: 17.2%, control: 2.7%; p<0.001), and ventilator requirement (laser: 27.7%, control: 13.5%; p=0.013). Laser treatment was not associated with any of the outcomes at both follow-up time points. Further research is needed to develop patient reported outcome measures that are more sensitive to the clinical changes experienced by burn survivors receiving laser treatment.

Multicenter evaluation of the Vetscan Imagyst system using Ocus 40 and EasyScan One scanners to detect gastrointestinal parasites in feces of dogs and cats.

The Vetscan Imagyst system (Zoetis) is a novel, artificial intelligence-driven detection tool that can assist veterinarians in the identification of enteric parasites in dogs and cats. This system consists of a sample preparation device, an automated digital microscope scanner, and a deep-learning algorithm. The EasyScan One scanner (Motic) has had good diagnostic performance compared with manual examinations by experts; however, there are drawbacks when used in veterinary practices in which space for equipment is often limited. To improve the usability of this system, we evaluated an additional scanner, the Ocus 40 (Grundium). Our objectives were to 1) qualitatively evaluate the performance of the Vetscan Imagyst system with the Ocus 40 scanner for identifying Ancylostoma, Toxocara, and Trichuris eggs, Cystoisospora oocysts, and Giardia cysts in canine and feline fecal samples, and 2) expand the assessment of the performance of the Vetscan Imagyst system paired with either the Ocus 40 or EasyScan One scanner to include a larger dataset of 2,191 fecal samples obtained from 4 geographic regions of the United States. When tested with 852 canine and feline fecal samples collected from different geographic regions, the performance of the Vetscan Imagyst system combined with the Ocus 40 scanner was correlated closely with manual evaluations by experts. Sensitivities were 80.0‒97.0% and specificities were 93.7‒100.0% across the targeted parasites. When tested with 1,339 fecal samples, the Vetscan Imagyst system paired with the EasyScan One scanner successfully identified the targeted parasite stages; sensitivities were 73.6‒96.4% and specificities were 79.7‒100.0%.

Comparison of DXA-based versus CT-based indices to predict prevalent fracture history in men with spinal cord injury.

Fracture risk prediction remains challenging in adults with spinal cord injury. Here, we compare the ability of CT- and DXA-derived indices to discriminate between those with and without prevalent osteoporotic fracture. Novel CT-derived indices may offer improved assessment of fragility fracture risk as well as improved monitoring of response to therapies. INTRODUCTION: Individuals with spinal cord injury are particularly susceptible to osteoporosis. As advanced imaging techniques become more readily available clinically, there is limited information on the relative strength of various outcomes for fracture risk prediction. The purpose of this study was to compare the ability of DXA-based versus CT-based indices to predict prevalent fracture history in adults with spinal cord injury. METHODS: Thirty-six men with known SCI underwent dual energy X-ray absorptiometry and computed tomography assessments of the lower extremities. We used age-adjusted area under the curve models to compare the predictive value for each bone parameter to identify prevalent fracture history. RESULTS: CT-based indices outperformed DXA-based indices at all sites. The site with the highest AUC was the trabecular BMD at the proximal tibial epiphysis. CONCLUSIONS: CT imaging may have clinical utility to improve fracture risk prediction in adults with SCI. More work is needed to confirm these findings and to assess the value of CT-based indices to predict incident fracture, monitor longitudinal bone loss, and monitor response to various therapies, both pharmacological and rehabilitation.

Association between weekly exercise minutes and resting IL-6 in adults with chronic spinal cord injury: findings from the fracture risk after spinal cord injury exercise study.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To assess associations between weekly aerobic exercise minutes and resting interleukin-6 (IL-6), C-reactive protein (CRP), or leptin levels in adults with chronic spinal cord injury (SCI). SETTING: Three hundred and forty-four community-dwelling men and women with SCI duration of > 1 year. METHODS: CRP, IL-6, and leptin levels were quantified by ultra-sensitive enzyme-linked immunoassay. Smoking, medication use, comorbidities, and aerobic exercise minutes per week were assessed by self-reported questionnaire. Body composition was determined by whole-body dual-energy X-ray absorptiometry. Generalized linear models were used to assess associations. RESULTS: In multivariable modeling, resting IL-6 levels were 0.001 pg/mL lower for every 1 min of weekly aerobic exercise. IL-6 levels increased with increasing android-to-gynoid fat ratio, in active/ever smokers compared to never smokers, and in individuals with skin pressure injuries compared to those without. IL-6 levels were lower in active ibuprofen users compared to nonusers. We found no association between weekly exercise minutes and CRP or leptin when designing similar models. CONCLUSIONS: Increasing aerobic exercise minutes is associated with lower IL-6 levels in adults with chronic SCI when considering body composition, smoking, skin pressure injuries, and ibuprofen use. CRP and leptin did not demonstrate an association with exercise when considering the similar variables. The use of these biomarkers in assessing the therapeutic value of future exercise-related interventions will be paramount for meaningful health improvement among those with SCI. Although a large, prospective dataset, this cross-sectional study cannot assign causation. Future prospective studies are needed to confirm these findings.

Evolution of viral variants in remdesivir-treated and untreated SARS-CoV-2-infected pediatrics patients.

Detailed information on intrahost viral evolution in SARS-CoV-2 with and without treatment is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 from the upper respiratory tract of nine hospitalized children, three of whom were treated with remdesivir, revealed that remdesivir treatment suppressed viral load in one patient but not in a second infected with an identical strain without any evidence of drug resistance found. Reduced levels of subgenomic RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. These likely arose from within-host evolution, although superinfection cannot be excluded in one case. Although our dataset is small, observed sample-to-sample heterogeneity in variant frequencies across four of nine patients suggests the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalization could compromise the penetration of remdesivir into the lung, limiting the drugs in vivo efficacy, as has been observed in other lung infections.

Parents as Advocates for Pediatric Palliative Care.

Caring for a child with a serious or life-limiting illness presents many challenges for families and health care providers. Through that experience (and, many times, as it ends), parents are compelled to find and make meaning from their ultimate loss and the many losses along the way. In this Advocacy Case Study, we describe the experiences that led a bereaved mother to seek to harness the insights from her own family's loss to help support other families facing the challenges and complexities of a child's serious illness. Her family initially established a family foundation to advocate for palliative care. She later partnered with her family's general pediatrician and the American Academy of Pediatrics to educate providers and bring parent voices to health care provider discussions. This work eventually led to the development of the Courageous Parents Network, a nonprofit focused on making these parent and provider voices widely available to families and providers through a Web-based collection of videos, blogs, podcasts, and printable guides. Through these insights, the organization addresses feelings of isolation, anxiety, and grief. In addition, these voices illustrate the power and benefits of the growing acceptance of pediatric palliative care practices. Important lessons learned through these efforts include: (1) the power of stories for validation, healing, and understanding; (2) opportunity to extend the reach of pediatric palliative care through provider education and skill-building; (3) critical importance of the parent-provider advocacy collaboration; and (4) necessity of market testing and continuous improvement.

SARS-CoV-2 evolution during treatment of chronic infection.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.

Further evaluation and validation of the VETSCAN IMAGYST: in-clinic feline and canine fecal parasite detection system integrated with a deep learning algorithm.

BACKGROUND: Fecal examinations in pet cats and dogs are key components of routine veterinary practice; however, their accuracy is influenced by diagnostic methodologies and the experience level of personnel performing the tests. The VETSCAN IMAGYST system was developed to provide simpler and easier fecal examinations which are less influenced by examiners' skills. This system consists of three components: a sample preparation device, an automated microscope scanner, and analysis software. The objectives of this study were to qualitatively evaluate the performance of the VETSCAN IMAGYST system on feline parasites (Ancylostoma and Toxocara cati) and protozoan parasites (Cystoisospora and Giardia) and to assess and compare the performance of the VETSCAN IMAGYST centrifugal flotation method to reference centrifugal and passive flotation methods. METHODS: To evaluate the diagnostic performance of the scanning and algorithmic components of the VETSCAN IMAGYST system, fecal slides were prepared by the VETSCAN IMAGYST centrifugal flotation technique with pre-screened fecal samples collected from dogs and cats and examined by both an algorithm and parasitologists. To assess the performance of the VETSCAN IMAGYST centrifugal flotation technique, diagnostic sensitivity and specificity were calculated and compared to those of conventional flotation techniques. RESULTS: The performance of the VETSCAN IMAGYST algorithm closely correlated with evaluations by parasitologists, with sensitivity of 75.8-100% and specificity of 93.1-100% across the targeted parasites. For samples with 50 eggs or less per slide, Lin's concordance correlation coefficients ranged from 0.70 to 0.95 across the targeted parasites. The results of the VETSCAN IMAGYST centrifugal flotation method correlated well with those of the conventional centrifugal flotation method across the targeted parasites: sensitivity of 65.7-100% and specificity of 97.6-100%. Similar results were observed for the conventional passive flotation method compared to the conventional centrifugal flotation method: sensitivity of 56.4-91.7% and specificity of 99.4-100%. CONCLUSIONS: The VETSCAN IMAGYST scanning and algorithmic systems with the VETSCAN IMAGYST fecal preparation technique demonstrated a similar qualitative performance to the parasitologists' examinations with conventional fecal flotation techniques. Given the deep learning nature of the VETSCAN IMAGYST system, its performance is expected to improve over time, enabling it to be utilized in veterinary clinics to perform fecal examinations accurately and efficiently.

Medullary Serotonergic Binding Deficits and Hippocampal Abnormalities in Sudden Infant Death Syndrome: One or Two Entities?

Sudden infant death syndrome (SIDS) is understood as a syndrome that presents with the common phenotype of sudden death but involves heterogenous biological causes. Many pathological findings have been consistently reported in SIDS, notably in areas of the brain known to play a role in autonomic control and arousal. Our laboratory has reported abnormalities in SIDS cases in medullary serotonin (5-HT) receptor 1A and within the dentate gyrus of the hippocampus. Unknown, however, is whether the medullary and hippocampal abnormalities coexist in the same SIDS cases, supporting a biological relationship of one abnormality with the other. In this study, we begin with an analysis of medullary 5-HT1A binding, as determined by receptor ligand autoradiography, in a combined cohort of published and unpublished SIDS (n = 86) and control (n = 22) cases. We report 5-HT1A binding abnormalities consistent with previously reported data, including lower age-adjusted mean binding in SIDS and age vs. diagnosis interactions. Utilizing this combined cohort of cases, we identified 41 SIDS cases with overlapping medullary 5-HT1A binding data and hippocampal assessment and statistically addressed the relationship between abnormalities at each site. Within this SIDS analytic cohort, we defined abnormal (low) medullary 5-HT1A binding as within the lowest quartile of binding adjusted for age and we examined three specific hippocampal findings previously identified as significantly more prevalent in SIDS compared to controls (granular cell bilamination, clusters of immature cells in the subgranular layer, and single ectopic cells in the molecular layer of the dentate gyrus). Our data did not find a strong statistical relationship between low medullary 5-HT1A binding and the presence of any of the hippocampal abnormalities examined. It did, however, identify a subset of SIDS (~25%) with both low medullary 5-HT1A binding and hippocampal abnormalities. The subset of SIDS cases with both low medullary 5-HT1A binding and single ectopic cells in the molecular layer was associated with prenatal smoking (p = 0.02), suggesting a role for the exposure in development of the two abnormalities. Overall, our data present novel information on the relationship between neuropathogical abnormalities in SIDS and support the heterogenous nature and overall complexity of SIDS pathogenesis.

The impact of discharge contracture on return to work after burn injury: A Burn Model System investigation.

INTRODUCTION: Despite many advances in burn care, the development of extremity contracture remains a common and vexing problem. Extremity contractures have been documented in up to one third of severely burned patients at discharge. However, little is known about the long-term impact of these contractures. The purpose of this study was to examine the association of extremity contractures with employment after burn injury. METHODS: We obtained data from the Burn Model System database from 1994 to 2003. We included in the study cohort all adult patients who were working prior to injury and identified those discharged with and without a contracture in one of the major extremity joints (shoulder, elbow, wrist, hip, knee and ankle). We classified contracture severity according to mild, moderate and severe categories. We performed descriptive analyses and predictive modeling to identify injury and patient factors associated with return to work (RTW) at 6, 12, and 24 months. RESULTS: A total of 1,203 participant records met criteria for study inclusion. Of these, 415 (35%) had developed a contracture at discharge; 9% mild, 12% moderate, and 14% severe. Among 801 (67%) participants who had complete data at 6 months after discharge, 70% of patients without contracture had returned to work compared to 45% of patients with contractures (p < 0.001). RTW increased at each subsequent follow-up time point for the contracture group, however, it remained significantly lower than in no-contracture group (both p < 0.01). In multivariable analyses, female sex, non-Caucasian ethnicity, larger burn size, alcohol abuse, number of in-hospital operations, amputation, and in-hospital complications were associated with a lower likelihood of employment. In adjusted analyses, discharge contracture was associated with a lower probability of RTW at all 3 time points, although its impact significantly diminished at 24 months. CONCLUSIONS: This study indicates an association between discharge contracture and reduced employment 6, 12 and 24 months after burn injury. Among many other identified patient, injury, and hospitalization related factors that are barriers to RTW, the presence of a contracture at discharge adds a significant reintegration burden for working-age burn patients.

Utilization of lipopolysaccharide challenge in cynomolgus macaques to assess IL-10 receptor antagonism.

The current era of drug discovery has been marked by a significant increase in the development of immune modulating agents to address a range of diseases such as cancer, chronic inflammation, and other conditions of dysregulated immunity. Non-clinical evaluation of these agents in animal models can be challenging, as the presence of an active immune state is often required in order to detect the effects of the test agent. Modulation of interleukin (IL)-10 signaling represents this type of situation in that altering IL-10 action in vivo can be difficult to appreciate in the absence of an ongoing immune response. The study presented here reports on the use of lipopolysaccharide (LPS) challenge in cynomolgus macaques to induce predictable inflammatory cytokine responses. The results showed that IL-10 receptor (IL-10R) blockade with an antagonist monoclonal antibody (mAb) dramatically enhanced the LPS-induced cytokine response, thus demonstrating in vivo pharmacologic activity of this immunomodulatory antibody. We submit that this approach could be applied to other cases where the intent of a candidate therapeutic is to modulate components of inflammatory cytokine responses.

Maternal Smoking Before and During Pregnancy and the Risk of Sudden Unexpected Infant Death.

OBJECTIVES: Maternal smoking during pregnancy is an established risk factor for sudden unexpected infant death (SUID). Here, we aim to investigate the effects of maternal prepregnancy smoking, reduction during pregnancy, and smoking during pregnancy on SUID rates. METHODS: We analyzed the Centers for Disease Control and Prevention Birth Cohort Linked Birth/Infant Death Data Set (2007-2011: 20 685 463 births and 19 127 SUIDs). SUID was defined as deaths at <1 year of age with International Classification of Diseases, 10th Revision codes R95 (sudden infant death syndrome), R99 (ill-defined or unknown cause), or W75 (accidental suffocation or strangulation in bed). RESULTS: SUID risk more than doubled (adjusted odds ratio [aOR] = 2.44; 95% confidence interval [CI] 2.31-2.57) with any maternal smoking during pregnancy and increased twofold between no smoking and smoking 1 cigarette daily throughout pregnancy. For 1 to 20 cigarettes per day, the probability of SUID increased linearly, with each additional cigarette smoked per day increasing the odds by 0.07 from 1 to 20 cigarettes; beyond 20 cigarettes, the relationship plateaued. Mothers who quit or reduced their smoking decreased their odds compared with those who continued smoking (reduced: aOR = 0.88, 95% CI 0.79-0.98; quit: aOR = 0.77, 95% CI 0.67-0.87). If we assume causality, 22% of SUIDs in the United States can be directly attributed to maternal smoking during pregnancy. CONCLUSIONS: These data support the need for smoking cessation before pregnancy. If no women smoked in pregnancy, SUID rates in the United States could be reduced substantially.

Mutations in NRXN1 and NRXN2 in a patient with early-onset epileptic encephalopathy and respiratory depression.

Early infantile epileptic encephalopathy (EIEE) is a severe disorder associated with epilepsy, developmental delay and intellectual disability, and in some cases premature mortality. We report the case of a female infant with EIEE and strikingly suppressed respiratory dysfunction that led to death. Postmortem research evaluation revealed hypoplasia of the arcuate nucleus of the medulla, a candidate region for respiratory regulation. Genetic evaluation revealed heterozygous variants in the related genes NRXN1 (c.2686C>T, p.Arg896Trp) and NRXN2 (c.3176G>A, p.Arg1059Gln), one inherited from the mother with family history of sudden infant death syndrome (SIDS) and one from the father with family history of febrile seizures. Although there are no previous reports with the digenic combination of NRXN1 and NRXN2 variants, patients with biallelic loss of NRXN1 in humans and double neurexin 1α/2α knockout mice have severe breathing abnormalities, corresponding to the respiratory phenotype of our patient. These observations and the known interaction between the NRXN1 and NRXN2 proteins lead us to hypothesize that digenic variants in NRXN1 and NRXN2 contributed to the phenotype of EIEE, arcuate nucleus hypoplasia, respiratory failure, and death.

Decisional burden among parents of children with cancer.

BACKGROUND: Despite growing evidence and support for shared decision making, little is known about the experiences of parents who hold more active roles than they wish. METHODS: This was a prospective cohort study of 372 parents of children with cancer and their oncologists at 2 academic pediatric hospitals. Parents were surveyed within 12 weeks of the diagnosis, and they were assessed for associated factors and outcomes of holding a more active decision-making role than they preferred. Parents were asked about their preferred and actual roles in decision making. Oncologists were asked to estimate parental preferences. RESULTS: Most parents preferred to share decision making with the oncologist (64% [236 of 372]); however, 13% (49 of 372) preferred oncologist-led decision making. Most parents fulfilled their ideal decision-making role (66% [244 of 372]), but a notable minority were either more involved (14% [52 of 372]) or less involved than they preferred (20% [76 of 372]; P < .0001 [McNemar test]). Oncologists recognized parents' preferred roles in 49% of cases (167 of 341); 24% (82 of 341) of parents preferred more active roles than the oncologist recognized, and 27% (92 of 341) preferred less active roles than recognized. No parent or communication characteristics were found that were associated with parents' holding a more active role than desired in decision making. Parents who held more active roles in decision making than they wished had higher odds of decisional regret (odds ratio, 3.75; 95% confidence interval, 2.07-6.80; P < .0001). CONCLUSIONS: Although many parents fulfill their desired roles in decision making about their child's cancer, some are asked to take on more active roles than they wish. Holding a more active role than desired may lead to increased decisional regret.

Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor.

The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylation, and functional pathway analyses on serial biopsies of vincristine-treated CTVTs and found that regression occurs in sequential steps; activation of the innate immune system and host epithelial tissue remodeling followed by immune infiltration of the tumor, arrest in the cell cycle, and repair of tissue damage. We identified CCL5 as a possible driver of CTVT regression. Changes in gene expression are associated with methylation changes at specific intragenic sites. Our results underscore the critical role of host innate immunity in triggering cancer regression.

Outcome Trends of Adult Cancer Patients Receiving Inpatient Rehabilitation: A 13-Year Review.

OBJECTIVE: This study describes characteristics and trends of inpatient rehabilitation among cancer patients within the United States over a 13-yr period. DESIGN: This was a retrospective study of data from the Uniform Data System for Medical Rehabilitation from 2002 to 2014. Patients older than 17 yrs admitted to inpatient rehabilitation facilities with a diagnosis of malignant cancer were included. Trends of rehabilitation outcomes including length of stay, Functional Independence Measure (FIM) Instrument scores, and discharge location were examined. RESULTS: Data from 115,570 cancer patients were evaluated. Mean age was 66 ± 14 yrs and 49% were women. Mean length of stay decreased over time (2002: 14 days to 2014: 13 days; P < 0.0005). Patient's admission total FIM scores decreased over time (2002: 68 ± 18 to 2014: 61 ± 16; P < 0.0005). The FIM change score increased over time (2002: 19 ± 16 to 2014: 25 ± 17; P < 0.0005). The greatest significant functional gains occurred in self care and transfers. Most patients (>70%) were discharged to the community. CONCLUSIONS: Cancer patients receiving acute inpatient rehabilitation demonstrated significant improvements in functional outcomes from admission to discharge. Cancer patients became more independent in important activities of daily living, thereby potentially reducing caregiver burden and ensuring safer discharges back to the community. This study suggests potential benefit of inpatient rehabilitation for appropriate cancer patients.

Variables affecting functional improvement in chordoma patients admitted to an inpatient rehabilitation facility: A retrospective review.

STUDY DESIGN: Retrospective chart review of patients after surgical resection of chordoma admitted to an inpatient rehabilitation facility. OBJECTIVE: To evaluate the characteristics associated with improving two or more functional levels and therefore classifying as a substantial responder after an inpatient rehabilitation facility stay in post-resection chordoma patients. SETTING: Acute inpatient rehabilitation facility in the United States. METHODS: A total of 40 patients were admitted to an inpatient rehabilitation facility from 2010-2015 after chordoma resection. Demographics, tumor management information, lengths of stay and functional independence measures on admission and discharge were collected. Substantial responders were identified as individuals who improved two or more functional levels based on total FIM score change. Logistic regression was used to analyze the available data for association of quantitative and categorical variables with being a substantial responder. RESULTS: The categorical variables analyzed in this study (sex, readmission to an acute hospital, Charlson Comorbidity Index, tumor level, nerve sacrifice, recurrent tumor and metatases) were not associated with being a substantial responder. The quantitative variables age and length of stay at the inpatient rehabilitation facility were individually associated with being a substantial responder, while length of stay at the acute hospital was not. CONCLUSIONS: Patients who were younger were more likely to be classified as substantial responders. Patients with longer lengths of stay at the inpatient rehabilitation facility were also more likely to be classified as substantial responders.

Skeletal Muscle Injury Biomarkers: Assay Qualification Efforts and Translation to the Clinic.

Skeletal muscle (SKM) injury or myopathy results in structural or functional defects in SKMs that can be caused by variety of factors such as (1) genetic, (2) drug-induced, (3) disease progression (cachexia), or (4) aging (sarcopenia). Creatine kinase (CK) and aspartate transaminase (AST) activity assays have been routinely used as SKM injury biomarkers, but they lack sensitivity and tissue specificity. In collaboration with the Predictive Safety Testing Consortium, we evaluated the diagnostic performance of a muscle injury biomarker panel (MIP) compared to CK and AST and their correlation with the histology scores across 34 different rat studies. The MIP panel included the analytes skeletal troponin I, myosin light chain 3, fatty acid binding protein 3, and a CK mass (versus activity) assay. The area under the receiver operator characteristic curve for MIP panel ranged from 0.82 to 0.91 as compared to 0.71 and 0.82 for CK and AST activity assays, respectively. Because the MIP biomarkers outperformed the routine biomarkers, the European Medicines Agency and U.S. Food and Drug Administration posted Letters of Support encouraging further study of these analytes and acknowledged the utility of the MIP panel. Ongoing efforts are directed toward the application of the MIP panel biomarkers in clinical studies and regulatory qualification.

Characterization of Cancer Patients in Inpatient Rehabilitation Facilities: A Retrospective Cohort Study.

OBJECTIVES: To identify the types of cancer patients admitted to inpatient medical rehabilitation and to describe their rehabilitation outcomes. DESIGN: Retrospective cohort study. SETTING: U.S. inpatient rehabilitation facilities (IRFs). PARTICIPANTS: Adult patients (N=27,952) with a malignant cancer diagnosis admitted to an IRF with a cancer-related impairment between October 2010 and September 2012 were identified from the Uniform Data System for Medical Rehabilitation database. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic, medical, and rehabilitation characteristics for patients with various cancer tumor types were summarized using data collected from the Inpatient Rehabilitation Facility-Patient Assessment Instrument. Rehabilitation outcomes included the percentage of patients discharged to the community and acute care settings, and functional change from admission to discharge. Functional status was measured using the FIM instrument. RESULTS: Cancer patients constituted about 2.4% of the total IRF patient population. Cancer types included brain and nervous system (52.9%), digestive (12.0%), bone and joint (8.7%), blood and lymphatic (7.6%), respiratory (7.1%), and other (11.7%). Overall, 72% were discharged to a community setting, and 16.5% were discharged back to acute care. Patients with blood and lymphatic cancers had the highest frequency of discharge back to acute care (28%). On average, all cancer patient groups made significant functional gains during their IRF stay (mean FIM total change ± SD, 23.5±16.2). CONCLUSIONS: In a database representing approximately 70% of all U.S. patients in IRFs, we found that patients with a variety of cancer types are admitted to inpatient rehabilitation. Most cancer patients admitted to IRFs were discharged to a community setting and, on average, improved their function. Future research is warranted to understand the referral patterns of admission to postacute care rehabilitation and to identify factors that are associated with rehabilitation benefit in order to inform the establishment of appropriate care protocols.

Reduced serum myostatin concentrations associated with genetic muscle disease progression.

Myostatin is a highly conserved protein secreted primarily from skeletal muscle that can potently suppress muscle growth. This ability to regulate skeletal muscle mass has sparked intense interest in the development of anti-myostatin therapies for a wide array of muscle disorders including sarcopenia, cachexia and genetic neuromuscular diseases. While a number of studies have examined the circulating myostatin concentrations in healthy and sarcopenic populations, very little data are available from inherited muscle disease patients. Here, we have measured the myostatin concentration in serum from seven genetic neuromuscular disorder patient populations using immunoaffinity LC-MS/MS. Average serum concentrations of myostatin in all seven muscle disease patient groups were significantly less than those measured in healthy controls. Furthermore, circulating myostatin concentrations correlated with clinical measures of disease progression for five of the muscle disease patient populations. These findings greatly expand the understanding of myostatin in neuromuscular disease and suggest its potential utility as a biomarker of disease progression.