Systematic review and network meta-analysis (NMA) for cladribine tablets in achieving sustained disability improvement (SDI) in multiple sclerosis.

INTRODUCTION: This study was performed to compare probabilities of SDI on the Expanded Disability Status Scale (EDSS) in patients with relapsing-remitting multiple sclerosis (RRMS), treated with cladribine tablets (CT) or fingolimod (FTY), natalizumab (NAT), alemtuzumab (ALE) and ocrelizumab (OCR). CLINICAL RATIONALE FOR THE STUDY: Progression of neurological disability as measured by the EDSS has been a common endpoint in multiple sclerosis (MS) trials. Novel therapies can not only slow this process, but in some patients even reverse it. This effect can be measured by the sustained disability improvement (SDI) - an endpoint that seems to continuously gain importance in clinical practice. Despite that, SDI has rarely been explored as an outcome in MS clinical studies, mostly as post-hoc analyses from randomised trials or as retrospective analyses based on patient registry records. MATERIAL AND METHODS: A systematic review was conducted in Medline, Embase and Cochrane to identify clinical trials (RCT or non-RCT) evaluating 6-month SDI. An indirect comparison via network meta-analysis (NMA) was performed. Bayesian inference with Markov chains Monte Carlo methods were applied. RESULTS: Eight trials presenting SDI results and applicable for NMA were included: six non-RCTs, with control groups selected by propensity score matching, and two RCTs. NMA results revealed that probability of achieving 6-month SDI with CT was significantly higher compared to all other high efficacy disease-modifying drugs with available data - HR (95% Crl - Bayesian Credibility Interval) vs. FTY: 4.98 (2.11-11.79); vs. NAT: 3.12 (1.31-7.27); vs. ALE: 9.29 (3.40-25.21). The main results were confirmed in the sensitivity analyses. CONCLUSIONS: Of all considered therapies, treatment with cladribine tablets was associated with a higher probability of sustained disability improvement in RRMS patients. As this conclusion is based on available clinical data of limited quality, future studies, as well as real-world data, would be valuable to provide further evidence regarding the comparative effectiveness of RRMS therapies.

Frameless x-ray-based lead re-implantation after partial hardware removal of deep brain stimulation system with preservation of intracerebral trajectories.

BACKGROUND: Deep brain stimulation (DBS) is an established treatment for patients with medical refractory movement disorders with continuously increasing use also in other neurological and psychiatric diseases. Early and late complications can lead to revision surgeries with partial or complete DBS-system removal. In this study, we aimed to report on our experience with a frameless x-ray-based lead re-implantation technique after partial hardware removal or dysfunction of DBS-system, allowing the preservation of intracerebral trajectories. METHODS: We describe a surgical procedure with complete implant removal due to infection except for the intracranial part of the electrode and with non-stereotactic electrode re-implantation. A retrospective analysis of a patient series treated using this technique was performed and the surgical outcome was evaluated including radiological and clinical parameters. RESULTS: A total of 8 DBS-patients with lead re-implantation using the frameless x-ray-based method were enrolled in the study. A revision of 14 leads was performed, whereof a successful lead re-implantation could be achieved without any problems in 10 leads (71%). In two patients (one patient with dystonia and one patient with tremor), the procedure was not successful, so we placed both leads frame-based stereotactically. CONCLUSIONS: The described x-ray-based technique allows a reliable frameless electrode re-implantation after infection and electrode dysfunction and might represent an efficient alternative to frame-based procedures for lead revision making the preservation of intracerebral trajectories possible.

Cladribine tablets versus other disease-modifying oral drugs in achieving no evidence of disease activity (NEDA) in multiple sclerosis-A systematic review and network meta-analysis.

INTRODUCTION: Assuming full control of the relapsing-remitting multiple sclerosis (RRMS) is the main target for practitioners. Disease control could be defined as no clinical relapse, absence of 3-month confirmed disability progression expressed on the Expanded Disability Status Scale (EDSS), as well as no disease activity on magnetic resonance imaging (MRI). NEDA-3 (no evidence of disease activity) is a composite endpoint used primarily in clinical trials, comprising these 3 measurements of disease activity. The aim of this study is to compare cladribine tablets (CT) with oral disease-modifying drugs (DMDs) - fingolimod (FTY), dimethyl fumarate (DMF), and teriflunomide (TERI) - with regard to NEDA-3 and its clinical (relapse and disability progression) and MRI (no new T1 Gd+ lesions or no new T2 lesions or no enlargement of existing lesions) components occurrence during a 24-month follow-up. METHODS: In June 2018, a systematic review of MEDLINE, Embase and Cochrane database was performed. Due to the lack of head-to-head trials directly comparing cladribine tablets to oral drugs of interest, an indirect network meta-analysis (NMA) was applied, with placebo as a common comparator. NMA was performed with Bayesian approach and Markov chain Monte Carlo (MCMC) method for estimating posterior distributions. Additional data used in the analysis were taken from conference abstracts or post hoc analyses of pooled data from the clinical studies. RESULTS: Six randomised clinical trials (RCTs) presenting NEDA, with active treatment compared to placebo, were included in the NMA: CLARITY (CT), FREEDOMS and FREEDOMS II (FTY), CONFIRM and DEFINE (DMF) and TEMSO (TERI). The rate of NEDA-3 was significantly higher in cladribine tablets vs DMF: OR (odds ratio)=1.76 (95% CrI [credible intervals]: 1.02-3.03) and TERI: OR=2.78 (95% CrI: 1.60-4.83), but not vs FTY. For the MRI NEDA results were as follows - cladribine tablets vs DMF: OR=1.87 (95% CrI: 1.18-2.97); cladribine tablets vs TERI: OR=6.59 (95% CrI: 4.32-10.09); cladribine tablets vs FTY: OR=1.58 (95% CrI: 1.10-2.29). The comparison of clinical NEDA did not reach significance vs either DMF or TERI and evaluation vs FTY was not possible because of lack of data. CONCLUSIONS: Cladribine in the form of tablets was significantly more effective in achieving NEDA-3 than DMF and TERI, but there was no significant difference vs FTY. Cladribine tablets was more effective than all oral comparators considering the MRI NEDA. For clinical NEDA, the superiority vs DMF and vs TERI was not confirmed, and vs FTY evaluation was not possible.

Treatment of very large cranial defects with individually shaped polypropylene polyester knitwear prostheses: a series of 11 cases.

BACKGROUND: Very large cranial defects are not very common in neurosurgical practice and there is not any widely acknowledged standard of their treatment. One of the useful methods in such cases is individual forming of polypropylene-polyester knitwear. Such material was used in the past but before 2008 it was available only as standardized plates. Currently, it can be also produced as individually-shaped implants. The authors give their definition of very large cranial defects and present their experience with this cranioplastic method in such defects. METHODS: The authors collected data on 11 cases of patients with very large cranial defects, from a total of 156 cases, operated on in 5 Polish neurosurgical departments. The necessary implants were prepared for individual patients according to the data provided by a computed tomography examination and with the use of computer aided machining. RESULTS: All defects were larger than 120 cm2 (129 to 178 cm2) and exceeded 1/4 of the calvaria area. Patients were operated between 2008 to 2012. In all patients, a very good aesthetic result and correct skull reconstruction was achieved. The follow-up time in all cases exceeded 1 year and reached 4 years in one case. No complications were observed. CONCLUSIONS: Individually pre-shaped polypropylene-polyester knitwear prostheses are a good alternative to the existing cranioplasty methods, particularly in very large cranial defects.

[Epidemiology and diagnosis of breast cancer]. / Epidemiologia oraz diagnostyka raka piersi.

Breast cancer is the most common cancer in women. Family history of breast cancer, age at menarche, number of pregnancies and births, history of breast biopsies, use of hormone replacement therapy and time from the last menstrual period are the key events to note. In addition, a high percentage of cases has been demonstrated in women with a genetically conditioned cancer, i.e. mutations in genes BRCA1, BRCA2, syndromes of Li-Fraumeni, Cowden and Peutz-Jeghers. Over 90% of cases are local or regional when detected. The diagnostics approach consists of self-control, breast palpation by the doctor, breast imaging usually with ultrasound, mammography and magnetic resonance. To confirm the diagnosis, a fine-, core-needle or mammotome biopsy is performed. The final diagnosis is based on a wide panel of immunohistochemical and cytogenetic tests. Histological examination provides accurate assessment of the tumor type, grade, estrogen and progesterone hormone receptor status, HER2 overexpression and Ki67 proliferation index. The data makes possible to qualify to one of four groups of breast cancer biological subtypes, which allows individualized treatment of the patient.

Apigenin and hesperidin augment the toxic effect of doxorubicin against HepG2 cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies, with an increasing incidence. Despite the fact that systematic chemotherapy with a doxorubicin provides only marginal improvements in survival of the HCC patients, the doxorubicin is being used in transarterial therapies or combined with the target drug - sorafenib. The aim of the study was to evaluate the effect of natural flavonoids on the cytotoxicity of the doxorubicin against human hepatocellular carcinoma cell line HepG2. METHODS: The effect of apigenin and its glycosides - cosmosiin, rhoifolin; baicalein and its glycosides - baicalin as well as hesperetin and its glycosides - hesperidin on glycolytic genes expression of HepG2 cell line, morphology and cells' viability at the presence of doxorubicin have been tested. In an attempt to elucidate the mechanism of observed results, the fluorogenic probe for reactive oxygen species (ROS), the DNA oxidative damage, the lipid peroxidation and the double strand breaks were evaluated. To assess impact on the glycolysis pathway, the mRNA expression for a hexokinase 2 (HK2) and a lactate dehydrogenase A (LDHA) enzymes were measured. The results were analysed statistically with the one-way analysis of variance (ANOVA) and post hoc multiple comparisons. RESULTS: The apigenin and the hesperidin revealed the strongest effect on the toxicity of doxorubicin. Both flavonoids simultaneously changed the expression of the glycolytic pathway genes - HK2 and LDHA, which play a key role in the Warburg effect. Although separate treatment with doxorubicin, apigenin and hesperidin led to a significant oxidative DNA damage and double strand breaks, simultaneous administration of doxorubicin and apigenin or hesperidin abolished these damage with the simultaneous increase in the doxorubicin toxicity. CONCLUSION: The obtained results indicate the existence of a very effective cytotoxic mechanism in the HepG2 cells of the combined effect of doxorubicin and apigenin (or hesperidin), not related to the oxidative stress. To explain this synergy mechanism, further research is needed, The observed intensification of the cytotoxic effect of doxorubicin by this flavonoids may be a promising direction of the research on the therapy of hepatocellular carcinoma, especially in a chemoembolization.

Diagnostic value of lateral ventricle ratio: a retrospective case-control study of 112 acute subdural hematomas after non-severe traumatic brain injury.

PRIMARY OBJECTIVE: To evaluate correlation between the lateral ventricle ratio (LVR) and the risk of conservative treatment failure (CTF) among patients with acute subdural hematoma (ASDH) after non-severe traumatic brain injury (TBI), we retrieved from the hospital database and performed a retrospective analysis of 1339 cases with TBI treated during the 2008-2016 period. METHODS AND PROCEDURES: 112 patients with ASDH, GCS≥ 9 and initial conservative treatment were enrolled. They were divided according to the final treatment method applied (surgical or conservative). Clinical and radiological data was evaluated. We used ROC curve analysis and multivariate logistic regression model to identify risk factors of CTF. MAIN OUTCOMES AND RESULTS: LVR higher than 1.48 calculated on admission CT scans was the strongest predictor of CTF, with sensitivity of 78.9% and specificity of 93.5% (AUC: 0.774-0.994). LVR, prolonged prothrombin time and coexisting traumatic subarachnoid hemorrhage were independent risk factors. CONCLUSIONS: Despite limitations, study results support the view that patients after non-severe TBI with ASDH and with lateral ventricle asymmetry, defined as LVR> 1.48, require surgical treatment. LVR seems to be indirect, but still the closest method to quantify intracranial compliance. Thus, in the selected group of patients without clinical symptoms of critically diminished compensatory reserve, LVR could indicate those who need a surgical decompression.

Intracerebral electroencephalography in targeting anterior thalamic nucleus for deep brain stimulation in refractory epilepsy.

BACKGROUND: Results of DBS of ATN in refractory epilepsy depend on accuracy of the electrode's location. We searched for characteristic intraoperative, intracerebral EEG recording pattern from anterior thalamic nuclei (ATNs) as a biological marker for verifying the electrode's position. METHODS: There were six patients with refractory epilepsy scheduled for deep brain stimulation (DBS) procedure. At surgery, to map the target, we recorded EEG from each lead of DBS electrodes. One patient underwent a 24 hours EEG with continuous recording from both ATNs before internalization of stimulator units. RESULTS: In all patients we recorded spontaneous bioelectric activity of ATNs. The pattern of the recording from the ATN was similar in all cases. In the one patient where 24-hour recording was done with simultaneous scalp EEG, a complex partial seizure was captured. CONCLUSION: This is the first report of using DBS electrode for intraoperative EEG recordings from the ATN in patients with refractory epilepsy. Since we managed to find the characteristic pattern of bioelectric activity of ATN, this technique seems to be a promising method for targeting this structure during the operation.

Intracranial video-EEG monitoring in presurgical evaluation of patients with refractory epilepsy.

OBJECTIVE: Reviewing our experience in intracranial video-EEG monitoring in the presurgical evaluation of patients with refractory epilepsy. METHODS: We report on 62 out of 202 (31%) patients with refractory epilepsy, who underwent a long term video-EEG monitoring (LTM). The epileptogenic zone (EZ) was localised either based on the results of LTM or after intracranial EEG recordings from depth, subdural or foramen ovale electrodes. The decision on the location of the electrodes was based upon semiology of the seizures, EEG findings and the lesions visualised in MRI brain scan. Intraoperative corticography was carried out before and right after the resection of the seizure onset zone. RESULTS: The video-EEG monitoring could localise EZ in 43 (69%) cases based. The remaining patients underwent invasive diagnostics: 10 (53%) had intracerebral depth electrodes, 6 (31%) depth and subdural and 3 (16%) foramen ovale electrodes. Intracranial video EEG recordings showed seizure focus in all the patients. Ten of them had EZ in mesial temporal structures, 4 in accessory motor area, 3 at the base of the frontal lobe and 2 in parietal lobe. There was one case of an asymptomatic intracerebral haematoma at the electrode. All patients were subsequently operated on. In 15 (79%) cases the seizures subsided (follow-up from 2 to 5 years), in 4 (21%) they decreased. CONCLUSIONS: The intracranial EEG is required in all patients with normal MRI (so-called nonlesional cases) in whom EZ is suspected to be located in the hippocampus, insula or in the basal parts of the frontal lobe.

New Flexible Flame Retardant Coatings Based on Siloxane Resin and Ethylene-Vinyl Chloride Copolymer.

This work presents the effectiveness of a phosphorus-containing flame retardant based on siloxane resin and ethylene-vinyl chloride copolymer as a back-coating of fabrics. The possibility of improving flame retardant efficiency of this composition by introducing fumed silica, montmorillonite, carbon nanotubes, and graphite was evaluated. The effect of each additive on the efficiency of the composition was examined separately. Flammability tests of flame retardant-coated fabrics (natural and synthetic) were carried out using pyrolysis combustion flow calorimetry (PCFC), cone calorimetry, and limiting oxygen index determination. An assessment of the ignitability of upholstered furniture containing flame retardant fabric, resistance to washing, antifungal activity, and some of the utility properties of the final newly-developed flame-retardant coating was conducted.

Isolated neurosarcoidosis mimicking intracranial tumours - Analysis of 3 cases.

Isolated neurosarcoidosis (INS), as a disease of low prevalence, is commonly overlooked in differential diagnosis, and its discovery on histopathological examination usually comes as a surprise. Preoperative diagnosis is difficult because the clinical picture of INS is non-specific. Its symptoms depend on the location of the lesions, and the MRI results are similar to those found in meningiomas or optic nerve gliomas. Although up to 5% of all sarcoidosis patients present with neurological symptoms, those with INS are exceptionally infrequently encountered. Three cases of INS are presented here, analysing their clinical course and radiological images, in order to determine characteristic traits that might lead to a correct diagnosis.

Activity of superoxide dismutase obtained from senile cataract lens - effect of diabetes mellitus.

The activity of Cu,Zn superoxide dismutase in the fluid obtained from eye lens capsules after cataract surgery was investigated in samples obtained from patients with senile cataract and with senile cataract combined with diabetes mellitus. Two parameters were measured and compared: the frequency of occurrence of detected superoxide dismutase activity and the relative activity of the enzyme in samples derived from senile cataract patients versus those from the patients affected additionally by diabetes mellitus. It was confirmed that the decrease of superoxide dismutase activity during cataract was additionally promoted by diabetes mellitus.

Evaluation of outcome after surgical treatment of cervical disc disease with DERO C-Disc PEEK cages.

BACKGROUND AND PURPOSE: To evaluate the efficacy of surgical treatment of cervical disc disease using a relatively novel type of cage, to assess the association between changes in cervical spine curvature and pain intensity as well as quality of life, to assess how often implants of different sizes were applied, and to analyze statistically the occurrence of surgical procedures performed on each spinal level. MATERIAL AND METHODS: The study group included 30 patients (19 [63%] women and 11 [37%] men), with a mean age of 48.8 years. Clinical assessment included, among other things, the visual analogue scale (VAS) for pain and the neck disability index (NDI). In addition to these questionnaires, each patient was neurologically examined pre- and postoperatively as well as during the follow-up visits one and three months after surgery. Radiological evaluation consisted of measurements of general and local lordosis of the cervical spine based on radiographs. RESULTS: Fifty-two cages were used during surgical procedures in the studied group of patients. Cages of seven out of ten different available sizes were used. Oblique cages (for lordosis correction) sized 4/6 mm (68%) and 5/7 mm (12%) were most often used. Implants of three sizes (8 mm, 10 mm, 7/9 mm) were not used. Surgical procedures most commonly involved levels C5/C6 (39%) and C6/C7 (33%). CONCLUSIONS: Surgical treatment of cervical disc disease with DERO C-Disc PEEK cages improved neurological condition of patients, decreased pain, improved quality of life and restored pathologically changed lordotic curvature of the cervical spine to near normal values. In the analyzed group of patients no significant correlations between changes in cervical spine curvature (general and local lordosis) and intensity of pain (VAS) as well as quality of life (NDI) were observed.