[New, innovative prognosis calculator for patients with metastatic spinal tumors]. / Új, innovatív prognóziskalkulátor áttétes gerinctumoros betegek számára.

Background and purpose: The aim of our research was to create a scoring system that predicts prognosis and recommends therapeutic options for patients with metastatic spine tumor. Increasing oncological treatment opportunities and prolonged survival have led to a growing need to address clinical symptoms caused by meta-stases of the primary tumor. Spinal metastases can cause a significant reduction in quality of life due to the caused neurological deficits. A scoring system that predicts prognosis with sufficient accuracy could help us to achieve personalised treatment options. Methods: Methods - We performed a retrospective clinical research of data from patients over 18 years of age who underwent surgery due to symptomatic spinal metastasis at the National Institute of Mental Disorders, Neurology and Neurosurgery between 2008 and 2018. Data from 454 patients were analysed. Survival analysis (Kaplan-Meier, log-rank, Cox model) was performed, network science-based correlation analysis was used to select the proper prognostic factors of our scoring system, such that its C value (predictive ability index) was maximized. Results: Multivariate Cox analysis resulted in the identification of 5 independent prognostic factors (primary tumour type, age, ambulatory status, internal organ metastases, serum protein level). Our system predicted with an average accuracy of 70.6% over the 10-year study period. Conclusion: Our large case series of surgical dataset of patients with symptomatic spinal metastasis was used to create a risk calculator system that can help in the choice of therapy. Our risk calculator is also available online at https://emk.semmelweis.hu/gerincmet.

Sterile, abscess-like cerebral lesion during trastuzumab therapy after HER2 status switch in a triple negative breast cancer patient: a case report and literature review.

BACKGROUND: Breast cancer is a global health problem - it is the most common malignancy among women. Triple negative breast cancers (TNBC) account for 10-20% of female breast cancer. Most TNBC cases confer poor prognosis. Brain metastasis appears in more than 15% in the triple negative breast cancer population, which causes serious decrease in survival. Changes of immunophenotype are not uncommon in breast cancer, offering new therapeutic options in cases where targetable proteins or pathways are being identified. CASE PRESENTATION: After five lines of chemotherapy and 82 months following the first diagnosis, our patient with brain metastatic triple negative breast cancer had human epidermal growth factor receptor 2 (HER2) genetic heterogeneity in the metastatic tissue sample interpreted as HER2 status conversion. After the removal of the metastasis, we started first line therapy for metastatic HER2 positive cancer with trastuzumab and paclitaxel. After the first cycle of trastuzumab, on day 8, she had a seizure, and neurosurgical examination showed an abscess-like lesion. The punctate proved to be sterile by microbiological and pathological examination, so we continued cytostatic therapy without the anti-HER2 antibody. 3 months later, we could not identify the previous abscess-like lesion in the control computer tomography (CT) scan, and our patient had no neurological deficits. CONCLUSION: We emphasize the importance of regular tissue confirmation of predictive markers in progressive tumorous disease even if our presented case is not unequivocally a "conversion case". Tumor subtype is determined according to algorithms and definitions published in guidelines, nevertheless, use of different guidelines may lead to controversial interpretation in cases where HER2 genetic heterogeneity is present. Furthermore, we suggest that seronegative, aseptic intracranial fluid effusion after the removal of a brain metastasis may possibly be a side effect of trastuzumab.

Research on the predicting power of the revised Tokuhashi system: how much time can surgery give to patients with short life expectancy?

OBJECT: The primary treatment option for symptomatic metastatic spinal tumors is surgery. Prognostic systems are designed to assist in the establishment of the indication and the choice of surgical methodology. The best-known prognostic system is the revised Tokuhashi system, which has a predictive ability of about 60%. In our study, we are attempting to find the reason for its poor predictive ability, despite its proper separation ability. METHODS: We have designed a one-center-based retrospective clinical trial, by which we would like to test the feasibility and the inaccuracy of the revised Tokuhashi system. In our database, there are 329 patients who underwent surgery. Statistical analysis was performed. RESULTS: A significant increase in survival time was observed in the 'conservative' category. Earlier studies reported OS 0.15 at the 180-day control time, in contrast with our 0.38 OS value. The literature suggested supportive care for this category, but in our population, every patient underwent surgery. Our population passes the 0.15 OS value on day 475. We propose an adjustment of the Tokuhashi category scores. We observed significant success in resolving pain. Motor functions were improved or stabilized compared to changes in vegetative dysfunction. CONCLUSION: According to our results, the Tokuhashi scoring system makes very conservative predictions and prefers non-surgical palliative or supportive care. Surgical treatment increases the life expectancy of patients in poor condition. We propose modifying the therapeutic options of the revised Tokuhashi system, taking into consideration modern spine surgery techniques.

Constructing and sampling partite, 3-uniform hypergraphs with given degree sequence.

Partite, 3-uniform hypergraphs are 3-uniform hypergraphs in which each hyperedge contains exactly one point from each of the 3 disjoint vertex classes. We consider the degree sequence problem of partite, 3-uniform hypergraphs, that is, to decide if such a hypergraph with prescribed degree sequences exists. We prove that this decision problem is NP-complete in general, and give a polynomial running time algorithm for third almost-regular degree sequences, that is, when each degree in one of the vertex classes is k or k - 1 for some fixed k, and there is no restriction for the other two vertex classes. We also consider the sampling problem, that is, to uniformly sample partite, 3-uniform hypergraphs with prescribed degree sequences. We propose a Parallel Tempering method, where the hypothetical energy of the hypergraphs measures the deviation from the prescribed degree sequence. The method has been implemented and tested on synthetic and real data. It can also be applied for χ2 testing of contingency tables. We have shown that this hypergraph-based χ2 test is more sensitive than the standard χ2 test. The extra sensitivity is especially advantageous on small data sets, where the proposed Parallel Tempering method shows promising performance.

[Neurosurgical treatment of tumors of the pineal region - literature review and overview of cases at OMIII]. / A pineális régió tumorainak idegsebészeti ellátása ­ irodalmi áttekintés és az OMIII beteganyagának vizsgálata.

Pineal region tumors account for less than 1% of adult supratentorial tumors. Their treatment requires a multimodality approach. Previously, the treatment of choice was direct surgery, which is associated with high surgical risk. Advances in minimally invasive techniques and onco-radiotherapy offer a safe and multimodal personalized therapy. The aim of our study was to describe the practice of our Institute based on combined endoscopic and radiotherapy techniques. We performed a retrospective clinical study. We processed data from 23 adult patients who underwent endoscopic third ventricle fenestration and pineal tumor biopsy between 2014 and 2023. Descriptive statistics, t-test, Fisher's exact test and Kaplan-Meier analysis were performed. Clinical improvement with endoscopic intervention was achieved in 78.3% of cases. Significant increase in preoperative performance status was observed in the postoperative period (p=2.755e-5), and radiotherapy resulted in regression or stable disease. Our results suggest a safe treatment with good clinical outcome and an excellent alternative to direct surgery.

Supplementary valproate therapy for glioma patients: An alternative opportunity to enhance the efficiency of radio-chemotherapy / A valproátterápia túlélésre gyakorolt hatása gliomás betegekben: Alternatív terápiás lehetoség a radiokemoterápia eredményességének javítására

Összefoglaló. Bevezetés: A gliomák, ezen belül a glioblastoma kezelése továbbra is megoldatlan onkológiai problémát jelent. A szekunder szimptómás epilepsziabetegség megjelenése pozitív prognosztikai faktornak tekintheto a korai diagnosztizálás és az antiepileptikumok potenciális tumorellenes hatásának köszönhetoen. A valproát túlélést hosszabbító hatása már több mint 20 éve az alap- és klinikai kutatások tárgyát képezi. Napjainkban ismert citotoxikus, proapoptotikus, antiangiogenetikus és hiszton-deacetiláz-gátló hatásmechanizmusa. Célkituzés: Kutatásunk célja a valproát túlélést hosszabbító hatásának vizsgálata egy hazai gliomás betegcsoportban. Módszer: Egycentrumos, retrospektív klinikai vizsgálatot végeztünk. A vizsgálatba 122 felnott beteget vontunk be, akiknél 2000 januárja és 2018 januárja között supratentorialis glioma miatt mutét történt, és rohamtevékenység miatt antiepileptikumot (valproát, levetiracetám, karbamazepin) szedtek. Egyúttal gyógyszert nem szedo kontrollcsoportot is kialakítottunk. A populációt vizsgálati és kontrollcsoportokra osztottuk 28 : 52 arányban. Leíró statisztikai, Kaplan-Meier- és log-rank analízist végeztünk. Eredmények: A vizsgált szövettani kategóriák túlélési analízise az irodalmi adatokkal megegyezo értékeket mutatott. A progressziómentes (PFS: p = 0,031) és a teljes (OS: p = 0,027) túlélés tekintetében is szignifikáns eltérés mutatkozott a különbözo antiepileptikumot szedo betegcsoportok között, amely még kifejezettebbé vált a valproátot és az egyéb antiepileptikumot szedo betegek túlélési idejének összehasonlítása során (PFS: p = 0,006; OS: p = 0,015). Következtetés: Vizsgálatunkban a valproát betegeink PFS- és OS-idejének meghosszabbodását eredményezte. Az irodalmi adatok és kutatásunk alapján megfontolandónak tartjuk a valproát elso vonalban történo alkalmazását onkoterápiában részesülo, epilepsziás, agyi gliomás betegekben. Orv Hetil. 2021; 162(24): 960-967. INTRODUCTION: Gliomas still prove to be a serious oncological problem. The presence of epilepsy may present a favorable prognosis due to early diagnosis and the potential antitumor effects of antiepileptic drugs. The survival prolongation effect of valproate has been studied for more than 20 years, nowadays its proapoptotic, anti-angiogenetic, cytotoxic and histone deacetylase inhibitory effects are well known. OBJECTIVE: Our goal was to investigate the survival-enhancing effects of valproate in a Hungarian patient cohort of primary brain tumors. METHOD: A single-center based retrospective clinical trial was designed. In our study, we included 122 patients harboring supratentorial glioma who underwent surgery and experienced seizures between 2000 January and 2018 January. The patients were grouped by the antiepileptic therapies and survival analysis was performed. RESULTS: The Kaplan-Meier curves of the histological categories showed the survival values consistent with the data of the literature. The progression-free (PFS: p = 0.031) and the overall (OS: p = 0.027) survival of the antiepileptic drug categories were significantly different. It was performed by comparing the valproate group and the population formed by the other groups which also showed a significant increase in the survival values (PFS: p = 0.006; OS: p = 0.015). CONCLUSION: Our results show that valproate increases the PFS and OS period of glioma patients in comparison to other antiepileptic drugs. Our data suggest that the use of valproic acid should be considered as a first-line antiepileptic agent in certain well-selected epileptic patients with glioma as a supplement to the oncotherapy. Orv Hetil. 2021; 162(24): 960-967.

Efficiently sampling the realizations of bounded, irregular degree sequences of bipartite and directed graphs.

Since 1997 a considerable effort has been spent on the study of the swap (switch) Markov chains on graphic degree sequences. All of these results assume some kind of regularity in the corresponding degree sequences. Recently, Greenhill and Sfragara published a breakthrough paper about irregular normal and directed degree sequences for which rapid mixing of the swap Markov chain is proved. In this paper we present two groups of results. An example from the first group is the following theorem: let [Formula: see text] be a directed degree sequence on n vertices. Denote by Δ the maximum value among all in- and out-degrees and denote by [Formula: see text] the number of edges in the realization. Assume furthermore that [Formula: see text]. Then the swap Markov chain on the realizations of [Formula: see text] is rapidly mixing. This result is a slight improvement on one of the results of Greenhill and Sfragara. An example from the second group is the following: let d be a bipartite degree sequence on the vertex set U ⊎ V, and let 0 < c1 ≤ c2 < |U| and 0 < d1 ≤ d2 < |V| be integers, where c1 ≤ d(v) ≤ c2: ∀v ∈ V and d1 ≤ d(u) ≤ d2: ∀u ∈ U. Furthermore assume that (c2 - c1 - 1)(d2 - d1 - 1) < max{c1(|V| - d2), d1(|U| - c2)}. Then the swap Markov chain on the realizations of d is rapidly mixing. A straightforward application of this latter result shows that when a random bipartite or directed graph is generated under the Erdos-Rényi G(n, p) model with mild assumptions on n and p then the degree sequence of the generated graph has, with high probability, a rapidly mixing swap Markov chain on its realizations.

Prognostic Factors of Surgical Complications and Overall Survival of Patients with Metastatic Spinal Tumor.

OBJECTIVE: Oncologic treatments increase the incidence of spinal metastases. Surgical treatment of spinal metastases results in a high complication rate, which must set against the expected benefits. The aim of this article was to study the effect of several prognostic factors on surgical complications and survival time using an extended database of patients with spinal metastases. METHODS: This retrospective study comprised 337 patients with spinal metastases who were surgically treated between 2008 and 2015. Demographic and clinical features, oncologic histories, surgical interventions, and end results were collected. Descriptive statistical methods were used to analyze the cohort of patients. Kaplan-Meier formula and log-rank test were used to examine overall survival times. RESULTS: Median overall survival time was 222 days (range, 175-274 days). Age, preoperative motor disorders, preoperative Frankel grade categories, Karnofsky performance scale, type of primary tumor, and presence of internal metastasis had a significant negative effect on overall survival. Complications such as bleeding or need for intensive care could be predicted preoperatively based on preoperative performance status, type of primary tumor, affected vertebral levels, and type of surgical interventions. CONCLUSIONS: Spinal metastatic disease is a challenging surgical problem. If the exact prognostic factors are known preoperatively, surgical outcome and overall survival can be predicted more precisely. Our results could provide a basis for a future multicenter prospective study to determine the best treatment protocol for patients with spinal metastases.

Analysis of Four Scoring Systems for the Prognosis of Patients with Metastasis of the Vertebral Column.

OBJECTIVE: Metastatic spinal diseases are common health problems and there is no consensus on the appropriate treatment of metastases in several conditions. Using clinical measures (e.g., survival time and functional status), prognosis prediction systems advise on the appropriate interventions. The aim of this article is to assess and compare 4 widely used scoring systems (revised Tokuhashi, Tomita, van der Linden, and modified Bauer scores) on a single-center cohort. METHODS: A retrospective study was designed of 329 patients who were subjected to surgery because of metastatic spinal diseases. Subpopulations according to the classifications of the 4 scoring systems were identified. The overall survival was calculated with the Kaplan-Meier formula. The difference between the survival curves of subpopulations was analyzed with log-rank tests. The consistency rates for the 4 scoring systems are calculated as well. RESULTS: The follow-up period was 8 years. The median survival time was 222 days. The overall survival of prognostic categories in 3 scoring systems was significantly different from each other, but we found no differences between the categories of the van der Linden system. In this cohort, the revised Tokuhashi system gave the best approximation for survival, with a mean predictive capability 60.5%. CONCLUSIONS: The evaluation of 4 standard scoring systems showed that 3 were self-consistent, although none of systems was able to predict the survival in our cohort. Based on the predictive capability, the revised Tokuhashi system may provide the best predictions with careful examination of individual cases.

Oral administration of pyrophosphate inhibits connective tissue calcification.

Various disorders including pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI), which are caused by inactivating mutations in ABCC6 and ENPP1, respectively, present with extensive tissue calcification due to reduced plasma pyrophosphate (PPi). However, it has always been assumed that the bioavailability of orally administered PPi is negligible. Here, we demonstrate increased PPi concentration in the circulation of humans after oral PPi administration. Furthermore, in mouse models of PXE and GACI, oral PPi provided via drinking water attenuated their ectopic calcification phenotype. Noticeably, provision of drinking water with 0.3 mM PPi to mice heterozygous for inactivating mutations in Enpp1 during pregnancy robustly inhibited ectopic calcification in their Enpp1-/- offspring. Our work shows that orally administered PPi is readily absorbed in humans and mice and inhibits connective tissue calcification in mouse models of PXE and GACI PPi, which is recognized as safe by the FDA, therefore not only has great potential as an effective and extremely low-cost treatment for these currently intractable genetic disorders, but also in other conditions involving connective tissue calcification.