Long-term outcomes five years after selective dorsal rhizotomy

<p>Abstract</p> <p>Background</p> <p>Selective dorsal rhizotomy (SDR) is a well accepted neurosurgical procedure performed for the relief of spasticity interfering with motor function in children with spastic cerebral palsy (CP). The goal is to improve function, but long-term outcome studies are rare. The aims of this study were to evaluate long-term functional outcomes, safety and side effects during five postoperative years in all children with diplegia undergoing SDR combined with physiotherapy.</p> <p>Methods</p> <p>This study group consisted of 35 children, consecutively operated, with spastic diplegia, of which 26 were Gross Motor Function Classification System (GMFCS) levels III–V. Mean age was 4.5 years (range 2.5–6.6). They were all assessed by the same multidisciplinary team at pre- and at 6, 12, 18 months, 3 and 5 years postoperatively. Clinical and demographic data, complications and number of rootlets cut were prospectively registered. Deep tendon reflexes and muscle tone were examined, the latter graded with the modified Ashworth scale. Passive range of motion (PROM) was measured with a goniometer. Motor function was classified according to the GMFCS and measured with the Gross Motor Function Measure (GMFM-88) and derived into GMFM-66. Parent's opinions about the children's performance of skills and activities and the amount of caregiver assistance were measured with Pediatric Evaluation Disability Inventory (PEDI).</p> <p>Results</p> <p>The mean proportion of rootlets cut in S2-L2 was 40%. Muscle tone was immediately reduced in adductors, hamstrings and dorsiflexors (p < 0.001) with no recurrence of spasticity over the 5 years. For GMFCS-subgroups I–II, III and IV–V significant improvements during the five years were seen in PROM for hip abduction, popliteal angle and ankle dorsiflexion (p = 0.001), capacity of gross motor function (GMFM) (p = 0.001), performance of functional skills and independence in self-care and mobility (PEDI) (p = 0.001).</p> <p>Conclusion</p> <p>SDR is a safe and effective method for reducing spasticity permanently without major negative side effects. In combination with physiotherapy, in a group of carefully selected and systematically followed young children with spastic diplegia, it provides lasting functional benefits over a period of at least five years postoperatively.</p

Health-related quality of life after vertebral or hip fracture: a seven-year follow-up study

<p>Abstract</p> <p>Background</p> <p>The negative impact of vertebral and hip low-energy fractures on health-related quality-of-life (HRQOL) has been demonstrated previously, but few prospective long-term follow-up studies have been conducted. This study aims to (i) investigate the changes and long-term impact of vertebral or hip fracture and between fracture groups on HRQOL in postmenopausal women prospectively between two and seven years after the inclusion fracture, (ii) compare HRQOL results between fracture and reference groups and (iii) study the relationship between HRQOL and physical performance, spinal deformity index and bone mineral density at seven-year follow-up.</p> <p>Methods</p> <p>Ninety-one women examined two years after a low-energy vertebral or hip fracture were invited to a new examination seven years after the diagnosis. HRQOL was examined using the SF-36 questionnaire and was compared with an age and sex-matched reference group. Physical function was assessed using tests and questionnaires. Bone mineral density was measured. Radiographs of the spine were evaluated using the visual semiquantitative technique. A longitudinal and cross-sectional design was used in this study. Statistical analyses included descriptive statistics, Student's <it>t</it>-tests, ANCOVA, and partial correlation.</p> <p>Results</p> <p>Sixty-seven women participated. In the 42 women (mean age 75.8, SD 4.7) with vertebral fracture as inclusion fracture, bodily pain had deteriorated between two and seven years and might be explained by new fracture. Remaining pronounced reduction of HRQOL was seen in all domains except general health and mental health at seven-year follow-up in women with vertebral fractures compared to the reference group (p < 0.05). All 25 women (mean age 75.0, SD 4.7) with hip fracture as inclusion fracture had no significant changes in HRQOL between two and seven years and did not differ from the reference group regarding HRQOL after seven years. The vertebral group had significantly lower values for bodily pain, vitality, role-emotional function and mental health compared to the hip group. HRQOL showed a positive relationship between physical activity, static balance and handgrip strength.</p> <p>Conclusion</p> <p>The long-term reduction of HRQOL in women with vertebral fracture emerged clearly in this study. The relationships between HRQOL and physical performance in women with vertebral and hip fracture raise questions for more research.</p

Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model

<p>Abstract</p> <p>Background</p> <p>Ectonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS) when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO) in a large animal model.</p> <p>Methods</p> <p>A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg). The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8) or saline (0.9 mg/ml, n = 8), twenty minutes after balloon inflation. Area at risk (AAR) was evaluated by <it>ex vivo </it>SPECT. IS and MO were evaluated by <it>ex vivo </it>MRI.</p> <p>Results</p> <p>No differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 ± 4.2% vs 69.4 ± 5.0%, p = NS) or MO (10.7 ± 4.8% vs 11.4 ± 4.8%, p = NS), but apyrase prolonged the post-ischemic reactive hyperemia.</p> <p>Conclusion</p> <p>Apyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction.</p

Genomic subtypes of breast cancer identified by array comparative genomic hybridization display distinct molecular and clinical characteristics

Abstract Introduction Breast cancer is a profoundly heterogeneous disease with respect to biologic and clinical behavior. Gene-expression profiling has been used to dissect this complexity and to stratify tumors into intrinsic gene-expression subtypes, associated with distinct biology, patient outcome, and genomic alterations. Additionally, breast tumors occurring in individuals with germline BRCA1 or BRCA2 mutations typically fall into distinct subtypes. Methods We applied global DNA copy number and gene-expression profiling in 359 breast tumors. All tumors were classified according to intrinsic gene-expression subtypes and included cases from genetically predisposed women. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to identify significant DNA copy-number aberrations and genomic subgroups of breast cancer. Results We identified 31 genomic regions that were highly amplified in > 1% of the 359 breast tumors. Several amplicons were found to co-occur, the 8p12 and 11q13.3 regions being the most frequent combination besides amplicons on the same chromosomal arm. Unsupervised hierarchical clustering with 133 significant GISTIC regions revealed six genomic subtypes, termed 17q12, basal-complex, luminal-simple, luminal-complex, amplifier, and mixed subtypes. Four of them had striking similarity to intrinsic gene-expression subtypes and showed associations to conventional tumor biomarkers and clinical outcome. However, luminal A-classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having a better prognosis, whereas the latter group included also luminal B and the majority of BRCA2-mutated tumors. The basal-complex subtype displayed extensive genomic homogeneity and harbored the majority of BRCA1-mutated tumors. The 17q12 subtype comprised mostly HER2-amplified and HER2-enriched subtype tumors and had the worst prognosis. The amplifier and mixed subtypes contained tumors from all gene-expression subtypes, the former being enriched for 8p12-amplified cases, whereas the mixed subtype included many tumors with predominantly DNA copy-number losses and poor prognosis. Conclusions Global DNA copy-number analysis integrated with gene-expression data can be used to dissect the complexity of breast cancer. This revealed six genomic subtypes with different clinical behavior and a striking concordance to the intrinsic subtypes. These genomic subtypes may prove useful for understanding the mechanisms of tumor development and for prognostic and treatment prediction purposes

Women in Charnley class C fail to improve in mobility to a higher degree after total hip replacement

BACKGROUND: The Charnley comorbidity classification organizes patients into 3 classes: (A) 1 hip involved, (B) 2 hips involved, and (C) other severe comorbidities. Although this simple classification is a known predictor of health-related quality of life (HRQoL) after total hip replacement (THR), interactions between Charnley class, sex, and age have not been investigated and there is uncertainty regarding whether A and B should be grouped together. METHODS: We selected a nationwide cohort of patients from the Swedish Hip Arthroplasty Register operated with THR due to primary osteoarthritis between 2008 and 2010. For estimation of HRQoL, we used the generic health outcome questionnaire EQ-5D of the EuroQol group. This consists of 2 parts: the EQ-5D index and the EQ VAS estimates. We modeled the EQ-5D index and the EQ VAS against the self-administered Charnley classification. Confounding was controlled for using preoperative HRQoL values, pain, and previous contralateral hip surgery. RESULTS: We found that women in class C had a poorer EQ-5D outcome than men. This effect was mostly due to the fact that women failed to improve in the mobility dimension; only 40% improved, while about 50% of men improved. Age did not interact with Charnley class. We also found that the classification performed best without splitting or aggregating classes. INTERPRETATION: Our results suggests that the self-administered Charnley classification should be used in its full capacity and that it may be interesting to devote special attention to women in Charnley class C

Concurrent and predictive validity of physical activity measurement items commonly used in clinical settings- data from SCAPIS pilot study.

BACKGROUND: As the understanding of how different aspects of the physical activity (PA) pattern relate to health and disease, proper assessment is increasingly important. In clinical care, self-reports are the most commonly used assessment technique. However, systematic comparisons between questions regarding concurrent or criterion validity are rare, as are measures of predictive validity. The aim of the study was to examine the concurrent (using accelerometry as reference) and predictive validity (for metabolic syndrome) of five PA questions. METHODS: A sample of 948 middle-aged Swedish men and women reported their PA patterns via five different questions and wore an accelerometer (Actigraph GT3X) for a minimum of 4 days. Concurrent validity was assessed as correlations and ROC-analyses. Predictive validity was assessed using logistic regression, controlling for potential confounders. RESULTS: Concurrent validity was low-to-moderate (r &lt;0.35 and ROC AUC &lt;0.7) with large misclassifications regarding time spent sitting/sedentary and in moderate-to vigorous PA. The predictive validity of the questions was good, and one question (PHAS) showed an 80 % decreased odds-ratio of having metabolic syndrome, after taking potential confounders into consideration. DISCUSSION: In this mixed sample of adults, both concurrent and predictive validity vaired between items and between measures of the physical activity pattern. The PHAS and WALK items are proposed for assessment of adherence to PA recommendations. CONCLUSION: Assessing PA patterns using self-report measures results in methodological problems when trying to predict individual risk for the metabolic syndrome, as the concurrent validity generally was low. However, several of the investigated questions may be useful for assessing risk at a group level, showing better predictive validity.SCAPI