We thank Gray et al for constructive comments to our article regarding vagotomy and Parkinson's disease (PD). 1 These authors have previously hypothesized that the appendix may be a primary source for pathological aggregation of a-synuclein with secondary spread to the brain 2 and contend that our results instead provide support for this hypothesis. In our study, we detected no protective effect following superselective vagotomy, in which only part of the stomach is surgically denervated. In the opinion of Gray et al, this largely excludes a gastric origin for PD initiation. However, this claim is based on the hypothesis that only a single gastrointestinal region serves as the point of initiation, which is not supported by the many reports of widespread a-synucleinopathy throughout the entire gastrointestinal tract. 3,4 Also, Holmqvist et al recently demonstrated that injections of PD brain lysate or recombinant fibrillar a-synuclein into the duodenum of rats is readily transported through the vagal nerve and reaches the dorsal motor nucleus of the vagus. 5 Thus, at least in animal models, it has now been demonstrated that a-synuclein originating outside the stomach and appendix propagates to the brainstem. To us, it seems more probable that many gastrointestinal regions (including the appendix) more or less simultaneously serve as initiation points in PD pathogenesis. In this explanatory framework, only a full truncal vagotomy would efficiently prevent ascending a-synuclein propagation to the dorsal motor nucleus of the vagus. Nevertheless, we have performed an initial reanalysis of our data set, in which we adjusted the analysis for the presence/absence of previous appendicitis. This did not change the risk estimates.Gray et al also wondered whether we were able to discriminate the PD risk reduction after selective vagotomy vis-avis superselective vagotomy. However, owing to issues regarding procedure code validation, we chose to group patients with truncal and selective vagotomy together. These procedures both require pyloroplasty, which has robust entries in our database. For this reason, we cannot comment on any difference in risk reduction between these two vagotomy subtypes. Furthermore, given that truncal and selective vagotomy are grouped together, the effect of truncal vagotomy might actually have been underestimated in our original report.In summary, we find the "appendix hypothesis" of Gray et al highly interesting and an inspiration for important future studies. We do, however, not believe that the observed lack of protection after superselective vagotomy in itself points to any particular gastrointestinal region as being a more important point of origin for further spread.
Summary: This article describes the triple use of autologous amnion graft as a new procedure in the treatment of myelomeningocele and in myelomeningocele with split cord malformation. The first amnion graft was used as a physical and mechanical barrier to protect the myelomeningocele (MMC) from desiccation and mechanical stress directly after birth. A second graft was used as a dura substitute to close the cerebrospinal fluid compartment. Autologous amnion seems to be the ideal dural graft for closure of an MMC and for an MMC with split cord malformation. A tension-free and watertight closure was obtained. With the epithelium side placed to the spinal cord and due to its beneficial effect on scar formation, the risk for tethering cord syndrome is reduced when using autologous amnion as a dural graft. The regenerative properties of autologous amnion may contribute to repair neural damage. Finally, a third amnion graft was placed beneath the perforator flap used to close the skin defect to provide a watertight barrier and to stimulate flap survival.
OBJECTIVE IDH-mutant diffuse low-grade gliomas (dLGGs; WHO grade 2) are often considered to have a more indolent course. In particular, in patients with 1p19q codeleted oligodendrogliomas, survival can be very long. Therefore, extended follow-up in clinical studies of IDH-mutant dLGG is needed. The authors’ primary aim was to determine results after a minimum 10-year follow-up in two hospitals advocating different surgical policies. In one center early resection was favored; in the other center an early biopsy and wait-and-scan approach was the dominant management. In addition, the authors present survival and health-related quality of life (HRQOL) in stratified groups of patients with IDH-mutant astrocytoma and oligodendroglioma. METHODS The authors conducted a retrospective, population-based, parallel cohort study with extended long-term follow-up. The inclusion criteria were histopathological diagnosis of IDH-mutant supratentorial dLGG from 1998 through 2009 in patients aged 18 years or older. Follow-up ended January 1, 2021; therefore, all patients had primary surgery more than 10 years earlier. In region A, a biopsy and wait-and-scan approach was favored, while early resections were advocated in region B. Regional referral practice ensured population-based data, since referral to respective centers was based strictly on the patient’s residential address. Previous data from EQ-5D-3L, European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, and EORTC BN20 questionnaires were reanalyzed with respect to the current selection of IDH-mutant dLGG and to molecular subgroups. The prespecified primary endpoint was long-term regional comparison of overall survival. Secondarily, between-group differences in long-term HRQOL measures were explored. RESULTS Forty-eight patients from region A and 56 patients from region B were included. Early resection was performed in 17 patients (35.4%) from region A compared with 53 patients (94.6%) from region B (p < 0.001). Characteristics at baseline were otherwise similar between cohorts. Overall survival was 7.5 years (95% CI 4.1–10.8) in region A compared with 14.6 years (95% CI 11.5–17.7) in region B (p = 0.04). When stratified according to molecular subgroups, there was only a statistically significant survival benefit in favor of early resection for patients with astrocytomas. The were no apparent differences in the different HRQOL measures between cohorts. CONCLUSIONS In an extended follow-up of patients with IDH-mutant dLGGs, early resection was associated with a sustained and clinically relevant survival benefit. The survival benefit was not counteracted by any detectable reduction in HRQOL.
This is the first randomised trial to compare the efficacy of HATCP graft with autograft in terms of stability of CLO in children. Because of problems with the HATCP the trial was stopped. We do not recommend HATCP graft in its current structure for use in unfixed CLOs. Cite this article: Bone Joint J 2016;98-B:1554-62.
Background Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected “high-risk” patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in two Scandinavian countries with similar public healthcare systems. Methods Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored. Results A total of 642 patients were included (male:female ratio 1.4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy. Conclusions Despite geographical population-based case selection, similar healthcare organization and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.
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