Citations

PurposeDespite the intra- and intertumoral heterogeneity seen in glioblastoma multiforme (GBM), there is little definitive data on the underlying cause of the differences in patient survivals. Serial imaging assessment of tumor growth allows quantification of tumor growth kinetics (TGK) measured in terms of changes in the velocity of radial expansion seen on imaging. Because a systematic study of this entire TGK phenotype—growth before treatment and during each treatment to recurrence —has never been coordinately studied in GBMs, we sought to identify whether patients cluster into discrete groups on the basis of their TGK.Patients and MethodsFrom our multi-institutional database, we identified 48 patients who underwent maximally safe resection followed by radiotherapy with imaging follow-up through the time of recurrence. The patients were then clustered into two groups through a k-means algorithm taking as input only the TGK before and during treatment.ResultsThere was a significant survival difference between the clusters ( P = .003). Paradoxically, patients among the long-lived cluster had significantly larger tumors at diagnosis ( P = .027) and faster growth before treatment ( P = .003) but demonstrated a better response to adjuvant chemotherapy ( P = .048). A predictive model was built to identify which cluster patients would likely fall into on the basis of information that would be available to clinicians immediately after radiotherapy (accuracy, 90.3%).ConclusionDichotomizing the heterogeneity of GBMs into two populations—one faster growing yet more responsive with increased survival and one slower growing yet less responsive with shorter survival—suggests that many patients who receive standard-of-care treatments may get better benefit from select alternative treatments.

Aims and Background HuR is a member of the family of ELAV (embryonic lethal abnormal vision)-like proteins that stabilize several cellular mRNAs by binding to AU-rich elements in the 3’ untranslated region of the mRNA. Cyclooxygenase-2 (COX-2) is a well known enzyme that promotes tumor growth and metastasis. Recent studies have shown that HuR can stabilize the mRNA of COX-2, and cytoplasmic expression of HuR is associated with increased COX-2 expression in some cancers. The aim of this study was to investigate the correlation between COX-2 and HuR in Ewing sarcoma. Methods The expression patterns for HuR and COX-2 were assessed via immunochemical analysis of 70 Ewing sarcoma samples. Results Nuclear HuR expression was observed in 12 of 70 (17.1%) cases, but cytoplasmic expression was not observed. COX-2 expression was seen in 25 of 70 (35.7%) samples. Nuclear HuR and COX-2 were simultaneously expressed in 8 of 70 (11.4%) samples. The expression of nuclear HuR was significantly associated with COX-2 expression (P = 0.014). Neither HuR nor COX-2 expression showed a correlation with age or sex. Conclusions COX-2 expression in Ewing sarcoma may not be directly related to mRNA stabilization by HuR. However, a correlation between COX-2 expression and nuclear HuR expression through indirect mRNA stabilization can be suggested.

Obesity is a risk factor for complications following many orthopaedic procedures. The purpose of this study was to investigate whether obesity was an independent risk factor increasing the rate of complications following periacetabular osteotomy (PAO) and to determine whether radiographic correction after PAO was affected by obesity.We retrospectively collected demographic, clinical and radiographic data on 280 patients (231 women; 82.5% and 49 men; 17.5%) who were followed for a mean of 48 months (12 to 60) after PAO. A total of 65 patients (23.2%) were obese (body mass index (BMI) > 30 kg/m2). Univariate and multivariate analysis demonstrated that BMI was an independent risk factor associated with the severity of the complications. The average probability of a patient developing a major complication was 22% (95% confidence interval (CI) 11.78 to 38.21) for an obese patient compared with 3% (95% CI 1.39 to 6.58) for a non-obese patient The odds of a patient developing a major complication were 11 times higher (95% CI 4.71 to 17.60, p < 0.0001) for an obese compared with a non-obese patient.Following PAO surgery, there was no difference in radiographic correction between obese and non-obese patients. PAO procedures in obese patients correct the deformity effectively but are associated with an increased rate of complications.Cite this article: Bone Joint J 2015;97-B:29–34.

SummaryBackground and AimsPSC is an autoimmune biliary inflammatory disorder that is often associated with inflammatory bowel disease (IBD), with 50%‐75% of patients with PSC having coexisting IBD, most commonly ulcerative colitis. Currently, no medical therapies have been shown to improve the disease course or slow its progression. However, ongoing research has resulted in a growing interest in the use of antibiotics for treatment of PSC, of which vancomycin is the most studied. In this review, we summarise the current evidence on the use of vancomycin in PSC and comment on future research areas of interest.MethodsA comprehensive PUBMED and EMBASE literature search for articles on vancomycin, PSC, therapeutic options and microbiome was performed.ResultsTwo randomised clinical trials, three case series and two case reports were included in the study. These include uncontrolled data from at least 98 patients that include promising improvements in biochemistry and imaging. Optimal dosing regimens are unclear.ConclusionVancomycin is one of the most studied antibiotics used in the treatment of PSC with promising results. There is not currently sufficient evidence to support treatment recommendations. Further research is needed to establish if vancomycin is a PSC treatment.

Abstract The synucleinopathies—Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure—result from distinct patterns of abnormal α‐synuclein aggregation throughout the nervous system. Autonomic dysfunction in these disorders results from variable involvement of the central and peripheral autonomic networks. The major pathologic hallmark of Parkinson's disease and dementia with Lewy bodies is Lewy bodies and Lewy neurites; of multiple system atrophy, oligodendroglial cytoplasmic inclusions; and of pure autonomic failure, peripheral neuronal cytoplasmic inclusions. Clinical manifestations include orthostatic hypotension, thermoregulatory dysfunction, gastrointestinal dysmotility, and urogenital dysfunction with neurogenic bladder and sexual dysfunction. Strong evidence supports isolated idiopathic rapid eye movement sleep disorder as a significant risk factor for the eventual development of synucleinopathies with autonomic and/or motor involvement. In contrast, some neurologically normal elderly individuals have Lewy‐related pathology. Future work may reveal protective or vulnerability factors that allow some patients to harbor Lewy pathology without overt autonomic dysfunction. © 2018 International Parkinson and Movement Disorder Society