One Week of Hospitalization Following Elective Hip Surgery Induces Substantial Muscle Atrophy in Older Patients

Objectives

Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women.

Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products

Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by a mutation in either the TSC1 or TSC2 tumour suppressor gene. The disease is characterized by a broad phenotypic spectrum that can include seizures, mental retardation, renal dysfunction and dermatological abnormalities. TSC2 encodes tuberin, a putative GTPase activating protein for rap1 and rab5. The TSC1 gene was recently identified and codes for hamartin, a novel protein with no significant homology to tuberin or any other known vertebrate protein. Here, we show that hamartin and tuberin associate physically in vivo and that the interaction is mediated by predicted coiled-coil domains. Our data suggest that hamartin and tuberin function in the same complex rather than in separate pathways.      

A decreased functional capacity of CD4+ T cells underlies the impaired DTH reactivity in old mice

The data presented in this paper show that the in vivo delayed-type-hypersensitivity (DTH) reaction to both H-2 and non-H-2 alloantigens declines with increasing age. It is also shown that cells generated in vitro are capable to transfer DTH to young naive syngeneic recipients. Using this in vitro system it could be demonstrated that cells from old CBA/Rij mice induced lower DTH responses than cells from young CBA/Rij mice. Depletion experiments with the effector T cell population showed that the DTH effector phase is mediated by CD4+ T cells. Lower responses in old mice were not due to increased CD8+ suppressor T cell activity, since after removal of the CD8+ T cells old CD4+ cells were still less effective in the generation of DTH effector T cells than young CD4+ cells. Addition of IL-2 containing supernatant to in vitro cultures did not improve the subsequent DTH response. From these data it can be concluded that the reduced DTH responses in old mice are not solely due to CD8+ suppressor cell activity and/or lack of IL-2, but that rather intrinsic defects of the CD4+ T cell population appear to play a major role in the impaired DTH reactivity during ageing.     

How Are Indeterminate Pulmonary Nodules at Diagnosis Associated with Survival in Patients with High-Grade Osteosarcoma?

BackgroundPulmonary metastases are a poor prognostic factor in patients with osteosarcoma; however, the clinical significance of subcentimeter lung nodules and whether they represent a tumor is not fully known. Because the clinician is faced with decisions regarding biopsy, resection, or observation of lung nodules and the potential impact they have on decisions about resection of the primary tumor, this remains an area of uncertainty in patient treatment. Surgical management of the primary tumor is tailored to prognosis, and it is unclear how aggressively patients with indeterminate pulmonary nodules (IPNs), defined as nodules smaller than 1 cm at presentation, should be treated. There is a clear need to better understand the clinical importance of these nodules.Questions/purposes(1) What percentage of patients with high-grade osteosarcoma and spindle cell sarcoma of bone have IPNs at diagnosis? (2) Are IPNs at diagnosis associated with worse metastasis-free and overall survival? (3) Are there any clinical or radiologic factors associated with worse overall survival in patients with IPN?MethodsBetween 2008 and 2016, 484 patients with a first presentation of osteosarcoma or spindle cell sarcoma of bone were retrospectively identified from an institutional database. Patients with the following were excluded: treatment at another institution (6%, 27 of 484), death related to complications of neoadjuvant chemotherapy (1%, 3 of 484), Grade 1 or 2 on final pathology (4%, 21 of 484) and lack of staging chest CT available for review (0.4%, 2 of 484). All patients with abnormalities on their staging chest CT underwent imaging re-review by a senior radiology consultant and were divided into three groups for comparison: no metastases (70%, 302 of 431), IPN (16%, 68 of 431), and metastases (14%, 61 of 431) at the time of diagnosis. A random subset of CT scans was reviewed by a senior radiology registrar and there was very good agreement between the two reviewers (κ = 0.88). Demographic and oncologic variables as well as treatment details and clinical course were gleaned from a longitudinally maintained institutional database. The three groups did not differ with regard to age, gender, subtype, presence of pathological fracture, tumor site, or chemotherapy-induced necrosis. They differed according to local control strategy and tumor size, with a larger proportion of patients in the metastases group presenting with larger tumor size and undergoing nonoperative treatment. There was no differential loss to follow-up among the three groups. Two percent (6 of 302) of patients with no metastases, no patients with IPN, and 2% (1 of 61) of patients with metastases were lost to follow-up at 1 year postdiagnosis but were not known to have died. Individual treatment decisions were determined as part of a multidisciplinary conference, but in general, patients without obvious metastases received (neo)adjuvant chemotherapy and surgical resection for local control. Patients in the no metastases and IPN groups did not differ in local control strategy. For patients in the IPN group, staging CT images were inspected for IPN characteristics including number, distribution, size, location, presence of mineralization, and shape. Subsequent chest CT images were examined by the same radiologist to reevaluate known nodules for interval change in size and to identify the presence of new nodules. A random subset of chest CT scans were re-reviewed by a senior radiology resident (κ = 0.62). The association of demographic and oncologic variables with metastasis-free and overall survival was first explored using the Kaplan-Meier method (log-rank test) in univariable analyses. All variables that were statistically significant (p < 0.05) in univariable analyses were entered into Cox regression multivariable analyses.ResultsFollowing re-review of staging chest CTs, IPNs were found in 16% (68 of 431) of patients, while an additional 14% (61 of 431) of patients had lung metastases (parenchymal nodules 10 mm or larger). After controlling for potential confounding variables like local control strategy, tumor size, and chemotherapy-induced necrosis, we found that the presence of an IPN was associated with worse overall survival and a higher incidence of metastases (hazard ratio 1.9 [95% CI 1.3 to 2.8]; p = 0.001 and HR 3.6 [95% CI 2.5 to 5.2]; p < 0.001, respectively). Two-year overall survival for patients with no metastases, IPN, or metastases was 83% [95% CI 78 to 87], 65% [95% CI 52 to 75] and 45% [95% CI 32 to 57], respectively (p = 0.001). In 74% (50 of 68) of patients with IPNs, it became apparent that they were true metastatic lesions at a median of 5.3 months. Eighty-six percent (43 of 50) of these patients had disease progression by 2 years after diagnosis. In multivariable analysis, local control strategy and tumor subtype correlated with overall survival for patients with IPNs. Patients who were treated nonoperatively and who had a secondary sarcoma had worse outcomes (HR 3.6 [95% CI 1.5 to 8.3]; p = 0.003 and HR 3.4 [95% CI 1.1 to 10.0]; p = 0.03). The presence of nodule mineralization was associated with improved overall survival in the univariable analysis (87% [95% CI 39 to 98] versus 57% [95% CI 43 to 69]; p = 0.008), however, because we could not control for other factors in a multivariable analysis, the relationship between mineralization and survival could not be determined. We were unable to detect an association between any other nodule radiologic features and survival.ConclusionThe findings show that the presence of IPNs at diagnosis is associated with poorer survival of affected patients compared with those with normal staging chest CTs. IPNs noted at presentation in patients with high-grade osteosarcoma and spindle cell sarcoma of bone should be discussed with the patient and be considered when making treatment decisions. Further work is required to elucidate how the nodules should be managed.Level of EvidenceLevel III, prognostic study.     

Cortical reafferentation following left subcortical hemorrhage: a serial functional MR study

A 48-year-old patient who had aphasia due to a left subcortical hemorrhage underwent three follow-up examinations to assess MR signal changes accompanying recovery. A word classification task was applied. During the 6-month follow-up period, we observed a dynamic change from negative toward positive blood oxygenation level-dependent MR signals, i.e., task-related reafferentation of eloquent cortices occurred. Clinical improvement from aphasia paralleled the MR signal changes.     

Preterm Infants 30–36 Weeks' Gestation in Victoria — Where Should They Be Delivered?

Summary: There is little doubt that very preterm infants <30 weeks' gestation should be born in level-3 perinatal centres. For preterm infants 30–36 weeks' gestation, however, the optimum place of birth is not so clear-cut. The aims of this study of livebirths 30–36 weeks' gestational age born in Victoria were to determine: 1) the proportions delivered outside level-3 centres, and 2) for infants born outside level-3 centres, the proportions transferred after birth to a level-3 nursery in the first days after birth. Data on the number of livebirths 30–36 weeks' gestational age in Victoria in the 3 years 1994–1996, inclusive, were supplied by the Victorian Perinatal Data Collection Unit. Data were obtained from the Newborn Emergency Transport Service (NETS) on all transfers within the first 3 days after birth to a level-3 centre for infants born outside level-3 centres. For the 3 years 1994–1996 there were 11,375 livebirths 30–36 weeks' gestational age in Victoria. The proportion born outside a level-3 perinatal unit was 57.9% overall, and rose with increasing gestational age, from 10.9% at 30 weeks to 69.0% at 36 weeks. Of the 6,587 livebirths outside a level-3 centre, 808 (12.3%) were transferred within the first 3 days after birth by NETS to a level-3 centre, the proportions falling with increasing maturity, being 73.7%, 48.5%, 28.4%, 26.9%, 18.8%, 11.8%, and 7.0% at 30, 31, 32, 33, 34, 35, and 36 weeks, respectively. These data may help medical practitioners when determining the place of delivery for infants 30–36 weeks' gestation.     

Understanding Atypical Emotions Among Children with Autism

Children with autism are said to be poor mind readers: They have a limited understanding of the role that mental states play in determining emotions and behavior. In this research, 23 high-functioning children from the autistic spectrum (M age 9 years 3 months), 42 6-year-old controls, and 43 10-year-old controls were presented with six emotion-evoking stories and they were asked to explain protagonists' typical and atypical emotions. In the case of typical emotions, as expected on the basis of the mindblind hypothesis, children from the autistic spectrum gave few mental state explanations, referring to fewer than even the 6-year-old control group. However, in the case of atypical emotions, the autistic group performed as well as the 10-year-old controls. Their explanations for the atypical emotions demonstrate that children from the autistic spectrum indeed have the capacity to mind read (with respect to both desires and beliefs), although they do not always use this capacity in the same way as normally developing children. It is argued that the mind-reading capacity of high-functioning children from the autistic spectrum might be basically intact; unused in everyday circumstances but not necessarily defective.