Inhaled Carbon Monoxide Provides Cerebral Cytoprotection in Pigs

Carbon monoxide (CO) at low concentrations imparts protective effects in numerous preclinical small animal models of brain injury. Evidence of protection in large animal models of cerebral injury, however, has not been tested. Neurologic deficits following open heart surgery are likely related in part to ischemia reperfusion injury that occurs during cardiopulmonary bypass surgery. Using a model of deep hypothermic circulatory arrest (DHCA) in piglets, we evaluated the effects of CO to reduce cerebral injury. DHCA and cardiopulmonary bypass (CPB) induced significant alterations in metabolic demands, including a decrease in the oxygen/glucose index (OGI), an increase in lactate/glucose index (LGI) and a rise in cerebral blood pressure that ultimately resulted in increased cell death in the neocortex and hippocampus that was completely abrogated in piglets preconditioned with a low, safe dose of CO. Moreover CO-treated animals maintained normal, pre-CPB OGI and LGI and corresponding cerebral sinus pressures with no change in systemic hemodynamics or metabolic intermediates. Collectively, our data demonstrate that inhaled CO may be beneficial in preventing cerebral injury resulting from DHCA and offer important therapeutic options in newborns undergoing DHCA for open heart surgery

Recomanacions per a l'entrenament i la prevenció de lesions en gimnastes de rítmica d'elit

Objectiu: Identificar els factors de risc en gimnastes de rítmica d'alt nivell i aconsellar recomanacions per prevenir el risc de lesions. Mètodes: Enquesta retrospectiva d'un any d'historial esportiu a 20 gimnastes que competien en l'àmbit nacional (mitjana d'edat, 17,1 anys; rang, 14,8-18,8 anys). Les hores d'entrenament per setmana, els minuts d'estiraments per dia i hores d'entrenament aeròbic per setmana es van analitzar com un risc potencial de factors de risc per a lesions esportives. La majoria de lesions registrades exigien deixar els entrenaments (time off); les lesions més severes (mínim de 7 dies sense activitat esportiva) eren lesions de parts blanes: tendó i/o múscul i fractures. Resultats: De les 20 gimnastes, 13 (65%) van tenir lesions que les van obligar a deixar els entrenaments i altres activitats esportives, 4 (20%) van ser lesions més severes. Van ser 17 (85%) les que van contestar que van presentar lesions musculotendinoses i 5 (25%) van patir fractures. Van ser 16 subjectes (80%) de la mostra els que van presentar lumbàlgia o fractures d'estrès lumbar, 8 amb necessitat de repòs. Una gimnasta va tenir una commoció cerebral. La regressió logística indica que l'entrenament i els estiraments, en gimnàstica rítmica estan associats a lesions de la unió musculotendinosa. En l'anàlisi multivariant es va trobar que els estiraments eren l'únic predictor independent de les lesions de la unió musculotendinosa; amb cada minut addicional es fa disminuir el risc aproximadament un 10% (p ≤ 0,01). Els exercicis d'estirament i de condicionament són els dos factors independents de predicció de fractures. El risc de fractura va ser valorat com a > 60% per cada hora setmanal addicional d'entrenament (odds ratio [OR] = 1,62; p = 0,03) i minva gairebé al 20% per cada minut addicional d'estiraments diaris (OR = 0,81; p = 0,04). Cap de les variables estudiades va ser predictiva de dolor o lesió lumbar. Conclusions: Les lesions en gimnàstica rítmica es podrien reduir incrementant el temps que es dedica als estiraments per dia (almenys 40 minuts), i limitant l'entrenament a un màxim de 6 hores per setmana

Injuries and training recommendations in elite rhythmic gymnastics

Objective: To identify risk factors for injury in rhythmic sportive gymnastics and to provide recommendations for reducing the risk of injury. Methods: A one-year retrospective survey of injuries in twenty national-level rhythmic gymnasts (ages 14.8 to 18.8 years; mean age 17.1 years). Hours of rhythmic gymnastics (RG) training per week, minutes of stretching per day, and hours of conditioning per week, were analyzed as potential risk factors for injury. Main outcome measures were injuries that required time off, major injuries (at least 7 days off), injuries to muscle-tendon units, and fractures. Results: Thirteen (65%) of 20 gymnasts sustained time-loss injuries, and 4 gymnasts (20%) reported major injuries. Seventeen (85%) gymnasts reported muscle-tendon unit injuries and 5 (25%) suffered fractures. Sixteen (80%) of the gymnasts reported back pain or stress fractures of the back, 8 of whom required time off training. One gymnast (5%) incurred a concussion. Logistic regression indicated that rhythmic gymnastics training and stretching were associated with muscle-tendon unit injury. On multivariate analysis, stretching was found to be the only independent predictor of muscle-tendon unit injuries with each additional minute lowering the risk by approximately 10% (p ≥ 0.01). Conditioning and stretching were both independent predictors of fractures. The risk of fracture was estimated to increase by over 60% for each additional hour of weekly conditioning (odds ratio = 1.62; p = 0.03) and decrease by almost 20% for each additional minute of daily stretching (odds ratio = 0.81; p = 0.04). None of the variables studied were predictive of back pain or injury. Conclusions: Injuries in rhythmic gymnastics may be reduced by increasing the amount of time spent stretching per day (at least 40 minutes), and limiting conditioning to a maximum of 6 hours per week

Hypergammaglobulinemia in the pediatric population as a marker for underlying autoimmune disease: a retrospective cohort study

Background: The significance of hypergammaglobulinemia as a marker of immune activation is unknown, as a differential diagnosis for hypergammaglobulinemia in children has not been adequately established. The goal of this study was to identify conditions associated with hypergammaglobulinemia in children, with the hypothesis that elevated immunoglobulin levels may precede or predict the development of autoimmune conditions. Methods: We reviewed the medical records for all children with IgG level ≥2000 mg/dL treated at a tertiary care children’s hospital from January 1, 2000 through December 31, 2009. We compared clinical and laboratory features of these patients, and developed an algorithm to predict the likelihood of underlying autoimmunity based on these characteristics. Results: After excluding children who had received IVIG, a total of 442 patients with hypergammaglobulinemia were identified. Of these, nearly half had autoimmune conditions, most frequently systemic lupus erythematosus and lupus-related disorders. Autoimmune gastrointestinal disorders such as inflammatory bowel disease were also common. Infectious diseases were the next largest category of diseases, followed with much less frequency by malignant, drug-related, and other conditions. In comparison with non-autoimmune conditions, patients with autoimmune disease had higher IgG levels, lower white blood cell counts, lower hemoglobin values, and lower C-reactive protein (CRP) levels. Multivariable logistic regression confirmed that CRP (P = 0.002), white blood cell count (P < 0.001), hemoglobin (P = 0.015), and female gender (P < 0.001) are independent risk factors for autoimmune disease in patients with high IgG levels. Conclusions: In a cohort of pediatric patients at a tertiary care children’s hospital, hypergammaglobulinemia was most commonly associated with autoimmune diseases. In female patients with hypergammaglobulinemia, the presence of leukopenia, anemia, and normal CRP was 95% predictive of underlying autoimmune disease

Assessment of axial bone rigidity in rats with metabolic diseases using CT-based structural rigidity analysis

Objectives: This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone. Methods: A total of 30 rats were divided equally into normal, ovariectomized, and partially nephrectomized groups. Cortical and trabecular bone segments from each animal underwent micro-CT to assess their average and minimum axial rigidities using structural rigidity analysis. Following imaging, all specimens were subjected to uniaxial compression and assessment of mechanically-derived axial rigidity. Results: The average structural rigidity-based axial rigidity was well correlated with the average mechanically-derived axial rigidity results (R$^2$ = 0.74). This correlation improved significantly (p < 0.0001) when the CT-based Structural Rigidity Analysis (CTRA) minimum axial rigidity was correlated to the mechanically-derived minimum axial rigidity results (R$^2$ = 0.84). Tests of slopes in the mixed model regression analysis indicated a significantly steeper slope for the average axial rigidity compared with the minimum axial rigidity (p = 0.028) and a significant difference in the intercepts (p = 0.022). The CTRA average and minimum axial rigidities were correlated with the mechanically-derived average and minimum axial rigidities using paired t-test analysis (p = 0.37 and p = 0.18, respectively). Conclusions: In summary, the results of this study suggest that structural rigidity analysis of micro-CT data can be used to accurately and quantitatively measure the axial rigidity of bones with metabolic pathologies in an experimental rat model. It appears that minimum axial rigidity is a better model for measuring bone rigidity than average axial rigidity

The Effect of Perioperative Ketorolac on the Clinical Failure Rate of Meniscal Repair

Background: There has been recent interest in the effect of nonsteroidal anti-inflammatory medications on musculoskeletal healing. No studies have yet addressed the effect of these medications on meniscal healing. Hypothesis The administration of ketorolac in the perioperative period will result in higher rates of meniscal repair clinical failure. Study design Cohort study; Level of evidence, 3. Methods: A total of 110 consecutive patients underwent meniscal repair at our institution between August 1998 and July 2001. Three patients were lost to follow-up, and the remaining 107 (mean age, 15.9 ± 4.4 years) had a minimum 5-year follow-up (mean follow-up, 5.5 years). Thirty-two patients (30%) received ketorolac perioperatively. The primary outcome measure was reoperation for continued symptoms of meniscal pathology. Asymptomatic patients were evaluated by the International Knee Documentation Committee (IKDC) Subjective Knee Form, Short Form–36 (SF-36) Health Survey, and Knee Outcome Osteoarthritis Score (KOOS). Results: Kaplan-Meier survivorship revealed no difference in reoperation rates with and without the administration of perioperative ketorolac (P = .95). There was an overall failure rate of 35% (37/107 patients), with a 34% failure rate in patients receiving ketorolac (11/32 patients). Multivariable Cox regression confirmed that age, duration of symptoms, meniscal tear type, fixation technique, concurrent anterior cruciate ligament repair, and ketorolac usage did not have an impact on the rate of failure (P > .05 for all; ketorolac use, P > .50). Female sex (P = .04) and medial location (P = .01) were predictive of an increased risk for reoperation. Conclusion: Failure of meniscal repair was not altered with the administration of perioperative ketorolac. Further work studying the effects of longer term anti-inflammatory use after meniscal repair is necessary before stating that this class of medications has no effect on meniscal healing. Clinical Relevance Results of this study suggest that nonsteroidal anti-inflammatory ketorolac can be administered perioperatively during a meniscal repair procedure to harness its benefits of decreased narcotic requirement, decreased pain, and shorter length of hospital stay without negatively influencing the long-term outcome of the surgery

Local stimulation of articular cartilage repair by transplantation of encapsulated chondrocytes overexpressing human fibroblast growth factor 2 (FGF-2) in vivo

Background Defects of articular cartilage are an unsolved problem in orthopaedics. In the present study, we tested the hypothesis that gene transfer of human fibroblast growth factor 2 (FGF-2) via transplantation of encapsulated genetically modified articular chondrocytes stimulates chondrogenesis in cartilage defects in vivo. Methods Lapine articular chondrocytes overexpressing a lacZ or a human FGF-2 gene sequence were encapsulated in alginate and further characterized. The resulting lacZ or FGF-2 spheres were applied to cartilage defects in the knee joints of rabbits. In vivo, cartilage repair was assessed qualitatively and quantitatively at 3 and 14 weeks after implantation. Results In vitro, bioactive FGF-2 was secreted, leading to a significant increase in the cell numbers in FGF-2 spheres. In vivo, FGF-2 continued to be expressed for at least 3 weeks without leading to differences in FGF-2 concentrations in the synovial fluid between treatment groups. Histological analysis revealed no adverse pathologic effects on the synovial membrane at any time point. FGF-2 gene transfer enhanced type II collagen expression and individual parameters of chondrogenesis, such as the cell morphology and architecture of the new tissue. Overall articular cartilage repair was significantly improved at both time points in vivo. Conclusions The data suggest that localized overexpression of FGF-2 enhances the repair of cartilage defects via stimulation of chondrogenesis, without adverse effects on the synovial membrane. These results may lead to the development of safe gene-based therapies for human articular cartilage defects

Effect of transforming growth factor-ß1 (TGF-ß1) released from a scaffold on chondrogenesis in an osteochondral defect model in the rabbit

Articular cartilage repair might be stimulated by the controlled delivery of therapeutic factors. We tested the hypotheses whether TGF-ß1 can be released from a polymeric scaffold over a prolonged period of time in vitro and whether its transplantation modulates cartilage repair in vivo. Unloaded control or TGF-ß1 poly(ether-ester) copolymeric scaffolds were applied to osteochondral defects in the knee joints of rabbits. In vitro, a cumulative dose of 9 ng TGF-ß1 was released over 4 weeks. In vivo, there were no adverse effects on the synovial membrane. Defects treated with TGF-ß1 scaffolds showed no significant difference in individual parameters of chondrogenesis and in the average cartilage repair score after 3 weeks. There was a trend towards a smaller area (42.5 %) of the repair tissue that stained positive for safranin O in defects receiving TGF-ß1 scaffolds. The data indicate that TGF-ß1 is released from emulsioncoated scaffolds over a prolonged period of time in vitro and that application of these scaffolds does not significantly modulate cartilage repair after 3 weeks in vivo. Future studies need to address the importance of TGF-ß1 dose and release rate to modulate chondrogenesis

Evidence-based decision support for pediatric rheumatology reduces diagnostic errors.

BACKGROUND: The number of trained specialists world-wide is insufficient to serve all children with pediatric rheumatologic disorders, even in the countries with robust medical resources. We evaluated the potential of diagnostic decision support software (DDSS) to alleviate this shortage by assessing the ability of such software to improve the diagnostic accuracy of non-specialists. METHODS: Using vignettes of actual clinical cases, clinician testers generated a differential diagnosis before and after using diagnostic decision support software. The evaluation used the SimulConsult® DDSS tool, based on Bayesian pattern matching with temporal onset of each finding in each disease. The tool covered 5405 diseases (averaging 22 findings per disease). Rheumatology content in the database was developed using both primary references and textbooks. The frequency, timing, age of onset and age of disappearance of findings, as well as their incidence, treatability, and heritability were taken into account in order to guide diagnostic decision making. These capabilities allowed key information such as pertinent negatives and evolution over time to be used in the computations. Efficacy was measured by comparing whether the correct condition was included in the differential diagnosis generated by clinicians before using the software ( unaided ), versus after use of the DDSS ( aided ). RESULTS: The 26 clinicians demonstrated a significant reduction in diagnostic errors following introduction of the software, from 28% errors while unaided to 15% using decision support (p \u3c 0.0001). Improvement was greatest for emergency medicine physicians (p = 0.013) and clinicians in practice for less than 10 years (p = 0.012). This error reduction occurred despite the fact that testers employed an open book approach to generate their initial lists of potential diagnoses, spending an average of 8.6 min using printed and electronic sources of medical information before using the diagnostic software. CONCLUSIONS: These findings suggest that decision support can reduce diagnostic errors and improve use of relevant information by generalists. Such assistance could potentially help relieve the shortage of experts in pediatric rheumatology and similarly underserved specialties by improving generalists\u27 ability to evaluate and diagnose patients presenting with musculoskeletal complaints. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02205086

A Modern Cohort of Duodenal Obstruction Patients: Predictors of Delayed Transition to Full Enteral Nutrition

Background:. A common site for neonatal intestinal obstruction is the duodenum. Delayed establishment of enteral nutritional autonomy continues to challenge surgeons and, since early institution of nutritional support is critical in postoperative newborns, identification of patients likely to require alternative nutritional support may improve their outcomes. Therefore, we aimed to investigate risk factors leading to delayed establishment of full enteral nutrition in these patients. Methods:. 87 patients who were surgically treated for intrinsic duodenal obstructions from 1998 to 2012 were reviewed. Variables were tested as potential risk factors. Median time to full enteral nutrition was estimated using the Kaplan-Meier method. Independent risk factors of delayed transition were identified using the multivariate Cox proportional hazards regression model. Results:. Median time to transition to full enteral nutrition was 12 days (interquartile range: 9–17 days). Multivariate Cox analysis identified three significant risk factors for delayed enteral nutrition: gestational age (GA) ≤ 35 weeks (P < .001), congenital heart disease (CHD) (P = .02), and malrotation (P = .03). Conclusions:. CHD and Prematurity are most commonly associated with delayed transition to full enteral nutrition. Thus, in these patients, supportive nutrition should strongly be considered pending enteral nutritional autonomy