Circulation 62 Suppl I Google Scholar. Circulation J Am Med Assoc Circulation 58 Suppl I Moulopoulus SD, Topaz S, Kolff WL Diastolic balloon pumping with carbon dioxide in the aorta — a mechanical assistance to the failing circulation. A wider spectrum of patient application Thorac Cardiovasc Surg Report of a cooperative trial. N Engl J Med Scheidt S Preservation of ischemic myocardium with intraaortic balloon pumping.
Reduced perioperative myocardial infarction with preoperative intra-aortic balloon counterpulsation. Br Heart J Long term follow-up of patients undergoing intraaortic balloon pumping counterpulsation and operation.
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Gonzalez, M. Percutaneous intraaortic balloon pumping: Initial experience. Intensive Care Med 8, — Download citation. Accepted : 24 August Issue Date : May RH and IDH2 p.
Percutaneous intraaortic balloon pumping: Initial experience
RH mutations [ 9 , 12 , 41 , 47 , 54 ]. Nevertheless, while the genetic profiles of brain astrocytomas have been largely established, those of uncommon IMAs remain to be defined. The present study aimed to correlate clinical, radiological and molecular data of IMAs to improve the current knowledge about the prognosis and molecular profile of these tumors. For the present study, the following inclusion criteria were defined: pathological diagnosis of LG or HG astrocytoma and spine location.
We excluded cases with a secondary supratentorial location at diagnosis. Grade III astrocytoma diagnosis was based on mitotic activity, high cellularity, nuclear atypia without features of glioblastoma necrosis and microvascular proliferation. To note, for the three grade III astrocytomas, as surgical resection was not complete according to surgical reports, we could not exclude undersampled glioblastoma. Twenty-six of the tumors were grade I pilocytic astrocytomas, 17 were grade II diffuse astrocytomas, 3 were grade III astrocytomas and 12 grade IV astrocytomas.
For the remaining cases, imaging features were collected from MRI reports. The imaging features assessed were location, signal T1 and T2 intensity, contrast enhancement, well-delineated vs. Clinical variables were collected based on clinical and surgical reports: age, gender, extent of surgery biopsy, partial or total resection , adjuvant treatments, follow-up duration and survival status.
For 54 cases, sufficient material from the primary resection samples was available for molecular analysis. For the remaining 7 cases, we used subsequent surgery samples to perform our molecular tests. For each RNA sample, more than 20, total mapped reads were considered, as recommended by the manufacturer ThermoFisher Scientific , with at least 5 control genes expressed over reads.
The algorithm uses normalized read coverage across amplicons to predict the copy number or ploidy state. Sample read coverage was compared to a baseline coverage constructed from 10 male control diploid DNA samples. Copy number variation CNV data were filtered to exclude regions with low confidence, as recommended by the manufacturer ThermoFisher.
For RNA analyses, reads were aligned with the hg19 human reference genome, and fusions were identified by using Ion Reporter software v5. Survival data were subjected to Kaplan-Meier analysis and the log-rank test. Multivariate Cox regression method was also applied. To include categorical variables in the multivariate models, we created dummy variables as follows.
In some cases, the total resection variable could be not included because of the problem of singular matrix decomposition for estimating model parameters. Kaplan-Meier curves of OS a, c and EFS b, d for all cases a, b and only for resected partial and gross total resection cases c, d. We observed heterogeneity in terms of the extent of surgical resection Table 1. Therefore, given this heterogeneity, we applied multivariate Cox survival analysis to assess the potential contribution of surgery considering the two dummy variables: biopsy and total resection to OS and EFS, independently of tumor grade.
No significant difference was observed between grade I pilocytic and grade II diffuse astrocytomas in terms of infiltration. As shown in Fig. Multivariate Cox regression combining grade I vs. II and two surgery variables biopsy and total resection revealed that only the absence of surgery i. Additional analyses showed that none of the other clinico-radiological variables listed in Table 2 contributed to the prognosis independent of the biopsy variable data not shown.
The molecular findings are summarized in Fig. Pathogenic hotspot mutations were identified: BRAF p. In contrast to brain astrocytomas, no hotspot IDH1 p.
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RH or IDH2 p. RH mutations were identified, and none of our cases harbored the 1p19q codeletion. The figure summarizes the clinico-pathological features and molecular alterations found in the 61 IMAs. The most frequent one was the H3F3A p. VE mutations. We compared the molecular profiles of IMAs described above to those of their brain counterparts using a series of gliomas analyzed in the routine diagnostic setting of our laboratory.
At least one molecular alteration was found in IDH1 p. For HG astrocytomas, no comparison between grade III astrocytomas of the brain and spine was possible because of the small number of samples from the spine.
However, all grade IV astrocytomas, either in the brain or in the spine, harbored at least one mutation. RH and non- IDH2 p. GV mutation case For the third case case 55 , no molecular alterations could be identified.
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VE mutation case The OS-related results detailed in Supplementary Table S4 a showed that only the H3K27M mutation made a significant contribution as a poor prognostic factor independent of the other variables in the model. Regarding EFS, Supplementary Table S4 b only the biopsy and the H3K27M mutation variables contributed significantly and negatively to prognosis, independently of the other variables in the model.
Integration of some clinico-radiological criteria with histology is commonly performed for the diagnosis of brain gliomas [ 20 , 49 ]. In the present study, we observed that these criteria were not helpful for IMAs.
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In brain gliomas, contrast enhancement is generally a common feature of HG gliomas [ 36 , 49 ], although it is a non-specific finding and can also be found in grade I pilocytic astrocytoma [ 31 , 33 , 40 , 49 ]. Interestingly, similar infiltrative patterns were observed in both grade I pilocytic and grade II diffuse IMAs, while grade I pilocytic and grade II diffuse brain astrocytomas are, by definition, well-circumscribed and diffuse neoplasms, respectively.
Our data are thus consistent with the literature and suggest that these classical radiological features are not helpful in the differential diagnosis between LG and HG IMAs. Nevertheless, even if the histological grade can be challenging to assess in the spine [ 32 , 41 ], it remains the most powerful prognostic marker [ 21 , 52 ], with LG IMAs associated with better outcomes than HG IMAs [ 11 , 21 , 55 ]. Our study showed that the tumor grade was associated with better OS, while EFS was strongly impacted by tumor grade and surgery, with a higher rate of disease progression in cases in which only biopsy could be performed.
In the literature, the impact of surgery on outcomes remains highly debated [ 16 , 39 ]. It is interesting to note that although the univariate analysis showed that the EFS was longer in grade I pilocytic IMAs than in grade II diffuse IMAs, the multivariate analysis showed that when the type of surgery was taken into account, the distinction between grade I and II did not add significant prognostic value. This result was explained by the fact that, within each group of patients treated with the same type of surgery, the difference in EFS between grades I and II was not statistically significant.
This result is consistent with Diaz et al. This outcome strongly contrasts with brain location, for which most grade I pilocytic astrocytomas are classically associated with better outcomes. IMAs also appear to be molecularly distinct from brain astrocytomas. However, the most frequent breakpoints found in IMAs were different than those usually found in brain grade I pilocytic astrocytomas, as also described by Faulkner et al.
The impact of the presence of the KIAABRAF fusion on prognosis remains debated [ 14 ], with some studies showing associations with better outcomes for pediatric LG gliomas [ 22 , 24 ]. Molecular alterations of grade II diffuse astrocytomas differ according to their location. IDH mutations were found in half of the brain astrocytoma cases, but only in 2 of the 61 IMAs with non-canonical mutations. IDH mutations are generally rare and mostly non-canonical in midline locations [ 35 ].
Previous reports of non-canonical IDH mutations in the spine are scarce and restricted to very few cases [ 8 , 9 , 12 , 41 , 54 ] with Takai et al. RS mutation that we found [ 47 ]. Among the 2 IDH-mutated cases, one died, and one progressed to a higher grade, as also reported by Takai et al. RS-mutated grade II spinal cord astrocytoma [ 47 ]. This finding could suggest that rare IDH mutations could be related to more aggressive behavior in LG IMAs, but this hypothesis must be confirmed in a larger cohort.
We observed BRAF p. Clinical trials involving FGFR inhibitors showed promising effects as targeted treatments for gliomas [ 15 , 18 ]. Because of their potentially clinical implications, it could be interesting to test these fusion genes. Anaplastic evolution occurred in only two grade II diffuse IMAs in this cohort, in agreement with previous studies that reported only one of fifteen grade II diffuse [ 39 ] and six of thirteen grade III IMAs progressing to a higher grade [ 38 ].
All of the H3F3A mutations identified in our cohort consisted of the recurrent hotspot p. We did not find any other mutations in genes encoding histone variants H3. Alvi et al. K27M mutations were identified in our cohort, in agreement with Shankar et al. In conclusion, these specific clinico-radiological and molecular landscapes of IMAs suggest that diagnostic algorithms commonly used in the brain must be reviewed to be confirmed as appropriate for those in the spine. Moreover, classical molecular alterations such as IDH mutations, EGFR and TERT promoter mutations, associated with diagnosis and prognosis in the brain, do not seem to occur with the same frequency, have the same implications in spine or at least, deserve further study.
In the brain, assessment of IDH mutations has been shown, as Ellezam et al. In the spine, because of the rarity of IDH mutations, the absence of IDH mutations cannot help to distinguish grade I pilocytic astrocytoma from grade II diffuse astrocytoma. RH in IMAs. In addition, the prognostic implications of molecular alterations in IMAs must be well characterized since implications similar to those observed in the brain cannot be established.
K27M mutation is an important molecular alteration to assess because of its prognostic implications. Mod Pathol —