Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multi-centre, retrospective, cohort study during the COVID-19 pandemic

Introduction. Treatment with cladribine tablets is indicated in highly active relapsing-remitting multiple sclerosis (RRMS). Cladribine tablets proved safe and effective in the pivotal CLARITY trial, but that trial included primarily treatment-naïve patients. In clinical practice however, cladribine tablets are often given to patients who have failed other treatments. Therefore, this study investigated the real-world safety and efficacy of cladribine tablets. Material and methods. We gathered data from nine MS clinical centres across Poland for patients with RRMS who started treatment with cladribine tablets from December 2019 to June 2022. Results. We enrolled 140 patients, with follow-up data available for 136 in year 1 and for 66 in year 2. At baseline, the mean age was 35.6 years, mean disease duration was 7.3 years, median EDSS score was 2.5, and 94% of patients were treatment- -experienced. Thirty-nine patients (27.9%) had undergone COVID-19, and 94 (67.1%) were vaccinated against COVID-19. The annualised relapse rate (ARR) decreased from 1.49 at baseline to 0.33 in year 1 (p < 0.001) and to 0.25 in year 2 (p < 0.001). The percentage of relapse-free patients increased from 11.5% at baseline to 70.2% in year 1 and 82.1% in year 2. The percentage of patients with active lesions decreased from 91.4% at baseline to 36.2% in year 1 and 18.2% in year 2. EDSS score remained stable or improved in 83.7% of patients in year 1 and 89.6% in year 2. No evidence of disease activity (NEDA-3) was achieved in 42.7% of patients in year 1 and 66.7% in year 2. Only one patient (0.72%) had grade 4 lymphopenia and 21 (15.1%) had grade 3 lymphopenia. Varicella zoster virus infections occurred in three patients. Eight patients discontinued treatment with cladribine: five due to inefficacy, one due to lymphopenia, and two due to a personal decision. Conclusions. Cladribine tablets proved safe and effective in a real-world cohort of treatment-experienced patients. However, the efficacy measures improved to a lesser extent in our cohort than in the pivotal clinical trial, which is probably due to a higher proportion of treatment-experienced patients in our cohort

Mechanical thrombectomy in acute stroke – Five years of experience in Poland

Objectives Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. Methods and results We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. Results Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% – emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b–TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization – in 30.7%, mRS of 0–2 – in 31.4% and mRS of 6 in 22% of cases. Conclusion Our results can help harmonize standards for MT in Poland according to international guidelines

Clinical course and outcome of SARS-CoV-2 infection in multiple sclerosis patients treated with disease-modifying therapies — the Polish experience

Introduction. The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited.Materials and methods. This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health.Results. There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used.Conclusions and clinical implications. Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs

Natural raw materials and compounds which affect tyrosinase activity

W ramach poniższej pracy przedstawiono przegląd związków oraz wyciągów z surowców pochodzenia roślinnego charakteryzujących się wpływem na tyrozynazę - enzym odpowiadający za produkcję melaniny w skórze oraz brązowienie żywności. Przegląd dotyczy badań wykonanych w ciągu ostatnich kilku lat (głównie 2012 – 2017).Charakterystyką objęto związki o znacznej aktywności hamującej (m.in. glabrydyna, 6,7,4’-trihydroksyizoflawon czy oksyresweratrol) lub aktywującej (apigenina, hyperozyd, ikaryna) jak również wybrane wyciągi roślinne wpływające na ten enzym.Większość z opisywanych związków i wyciągów to inhibitory tyrozynazy, co jest działaniem pożądanym, ze względu na możliwość wykorzystania go w przemyśle farmaceutycznym, kosmetycznym oraz produkcji żywności.This thesis presents the review of studies about plant compounds and extracts which affect tyrosinase - an enzyme involved in melanine synthesis and responsible for browning of food. This survey largely includes studies from last few years (mostly 2012 – 2017).The characteristic contains compounds of significant inhibitory (glabridine, 6,7,4’trihydroxyisoflavone, oxyresveratrol etc.) or stimulatory (apigenin, hyperosid, icariin) activity on tyrosinase as well as the selected plant extracts affecting tyrosinase.Most of described compounds and extracts are tyrosinase inhibitors, which activity is eligible because of possibilityof using in pharmaceutical, cosmetological and food industry

Serum Proteins Associated with Blood–Brain Barrier as Potential Biomarkers for Seizure Prediction

As 30% of epileptic patients remain drug-resistant, seizure prediction is vital. Induction of epileptic seizure is a complex process that can depend on factors such as intrinsic neuronal excitability, changes in extracellular ion concentration, glial cell activity, presence of inflammation and activation of the blood–brain barrier (BBB). In this study, we aimed to assess if levels of serum proteins associated with BBB can predict seizures. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2, S100B, CCL-2, ICAM-1, P-selectin, and TSP-2 were examined in a group of 49 patients with epilepsy who were seizure-free for a minimum of seven days and measured by ELISA. The examination was repeated after 12 months. An extensive medical history was taken, and patients were subjected to a follow-up, including a detailed history of seizures. Serum levels of MMP-2, MMP-9, TIMP-1, CCL-2, and P-selectin differed between the two time points (p p p p p = 0.0035, respectively). General linear model analyses determined the predictors of seizures. Levels of MMP-2, MMP-9, and CCL-2 were found to influence seizure count in 1, 3, 6, and 12 months of observation. Serum levels of MMP-2, MMP-9, and CCL-2 may be considered potential biomarkers for seizure prediction and may indicate BBB activation

Blood-Brain Barrier-Associated Proteins Are Elevated in Serum of Epilepsy Patients

Blood–brain barrier (BBB) dysfunction emerges as one of the mechanisms underlying the induction of seizures and epileptogenesis. There is growing evidence that seizures also affect BBB, yet only scarce data is available regarding serum levels of BBB-associated proteins in chronic epilepsy. In this study, we aimed to assess serum levels of molecules associated with BBB in patients with epilepsy in the interictal period. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2, S100B, CCL-2, ICAM-1, P-selectin, and TSP-2 were examined in a group of 100 patients who were seizure-free for a minimum of seven days and analyzed by ELISA. The results were compared with an age- and sex-matched control group. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2 and S100B were higher in patients with epilepsy in comparison to control group (p < 0.0001; <0.0001; 0.001; <0.0001; <0.0001, respectively). Levels of CCL-2, ICAM-1, P-selectin and TSP-2 did not differ between the two groups. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2 and S100B are elevated in patients with epilepsy in the interictal period, which suggests chronic processes of BBB disruption and restoration. The pathological process initiating epilepsy, in addition to seizures, is probably the factor contributing to the elevation of serum levels of the examined molecules

Blood-Brain Barrier-Associated Proteins Are Elevated in Serum of Epilepsy Patients

Blood–brain barrier (BBB) dysfunction emerges as one of the mechanisms underlying the induction of seizures and epileptogenesis. There is growing evidence that seizures also affect BBB, yet only scarce data is available regarding serum levels of BBB-associated proteins in chronic epilepsy. In this study, we aimed to assess serum levels of molecules associated with BBB in patients with epilepsy in the interictal period. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2, S100B, CCL-2, ICAM-1, P-selectin, and TSP-2 were examined in a group of 100 patients who were seizure-free for a minimum of seven days and analyzed by ELISA. The results were compared with an age- and sex-matched control group. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2 and S100B were higher in patients with epilepsy in comparison to control group (p < 0.0001; <0.0001; 0.001; <0.0001; <0.0001, respectively). Levels of CCL-2, ICAM-1, P-selectin and TSP-2 did not differ between the two groups. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2 and S100B are elevated in patients with epilepsy in the interictal period, which suggests chronic processes of BBB disruption and restoration. The pathological process initiating epilepsy, in addition to seizures, is probably the factor contributing to the elevation of serum levels of the examined molecules

A 3D Printed Anatomically Pre-Contoured Plate for the Treatment of Y-T Humeral Condylar Fractures: A Feline Cadaveric Study

(1) Background: Anatomically pre-contoured plates usually require only minimal or even no intraoperative contouring. For complex cases, such plates also assist the surgeon as an anatomical template during fracture reduction. In this study, we present our experience of using a 3D printing technology for the treatment of bicondylar humeral fractures in feline cadavers. (2) Methods: Surgeries were performed on 15 pairs of front limbs amputated at the scapula. The limbs were obtained from 15 adult cats without obvious pathology of the skeleton. After flexion of the elbow and subperiosteal elevation of the anconeus muscle, the humeral Y-T fractures were created using a bone chisel and mallet. A custom-made anatomically pre-contoured interlocking plate was used to reduce and stabilise the medial aspect of the humeral condyle to the humeral diaphysis. After reduction of the humeral condyle, a positional locking screw was then inserted from the medial to the lateral side and a straight 2.4/2.7 interlocking bone plate was used to stabilise the lateral part of the condyle to the humeral diaphysis. (3) Results: The length of the humerus ranged from 98.2 to 107.0 mm and did not differ significantly between the left and right bone. The diameter of the isthmus of the humeral condyle ranged from 5.2 to 5.5 mm and did not differ significantly between the left and right bone. In all 30 limbs, bicondylar fracture was accompanied by epicondylar comminution. In 7/30 limbs (4 left, 3 right) the fracture of the humeral shaft was also present. In the left limbs, the postoperative articular surface defect of the humeral condyle was small (2 mm) in 2/15 cases in which the condylar screw was incorrectly inserted. In the right limbs, the postoperative articular surface defect of the humeral condyle was small (<1 mm) in 14/15 cases and moderate (1–2 mm) in 1 case. (4) Conclusions: 3D printing and the technology of metal powder sintering offers a wide range of possibilities for the development of new surgical implants. The anatomically pre-contoured bone plate appears to be a valuable tool in the reduction and stabilisation of Y-T humeral fractures in adult domestic cats weighing 3.0 to 4.5 kg

Three-Dimensional Models of Liver Vessels for Navigation during Laparotomic Attenuation of Intrahepatic Portosystemic Shunt in Dogs

Laparotomic attenuation of an intrahepatic portosystemic shunt (IHPSS) is more difficult than an extrahepatic one, and results in a higher risk of complications because the identification of the aberrant vessel in the liver remains often a challenge. Excessive preparation and traction of the parenchyma results in trauma, bleeding, and prolonged surgery, which is what worsens the prognosis. Therefore, based on computed tomographic angiography, we printed 3-dimensional (3D) individual patient liver models, scaled 1:1, and used them for surgery planning and as a guide during intraoperative identification of the shunt in four dogs with IHPSS. The advantages of the 3D technology are simple and precise planning of the surgery, fast intraoperative identification of the shunt, and low invasive dissection of the liver parenchyma. We conclude that 3D technology can potentially raise the recovery rate. To the best of our knowledge, this was the first application of 3D models in the surgery of canine IHPSS

Comparison of the Ventral Approach to the Canine Hip Joint Using Gelpi Retractors and an Elastic O-Ring Wound Retractor

This study included 10 fresh adult cadavers of large breed dogs (6 males and 4 females). Their weight ranged from 25 to 45 kg (mean ± SD: 33.9 ± 6.2 kg). The breeds represented were crossbreed dogs (n = 5), German shepherds (n = 2), Bernese mountain dogs (n = 1), American Staffordshire terriers (n = 1), and Gordon setters (n = 1). Access to the target area and identification of the femoral head and neck was achieved with two Gelpi retractors inserted orthogonally and with the O-WR in all procedures. In each dog, the approach to the hip joint was made on the left and right sides. There was no significant difference in the area of the surgical wound bed between the two sides using either the Gelpi retractors (−0.52 ± 1.87 cm2; CI 95%: −1.86, 0.81 cm2; p = 0.398) or the O-WR (−0.27 ± 2.34 cm2; CI 95%: −1.94, 1.41 cm2; p = 0.729). The area of the surgical wound bed was 6.28 ± 1.72 cm2 (2.72–9.70 cm2) for the Gelpi retractors and 6.34 ± 1.81 cm2 (4.13–10.77 cm2) for the O-WR, and the difference between the Gelpi retractors and the O-WR was not significant (−0.06 ± 1.72 cm2; CI 95%: −0.86, 0.74 cm2; p = 0.879