Nowe możliwości leczenia wirusowego zapalenia wątroby typu C

Chronic hepatitis C (CHC) is the leading causes of chronic liver disease and its irreversible conse­quences: liver cirrhosis and hepatocellular carcino­ma. According to the estimates of the World Health Organization, about 1.5% (~71 million) of the global population exhibits the active infection of hepatitis C virus (HCV), and the number of deaths associated with its complications reaches 500,000 per year. Clinically, the disease may be insidious for many years, with mild and non characteristic symptoms. Diagnosis can be established only at the stage of advanced liver disease. Not rarely, serious extra­hepatic pathology develops following chronic HCV infection. Until 2014 the most commonly used anti­viral therapy consisted of combination of pegylated interferon and ribavirin. Its efficacy did not exceed 50%, and serious side effects were a significant ob­stacle to its use. Since 2015 new oral directly act­ing antiviral drugs (DAA) have been available in the treatment of CHC. They are characterized by a very favorable safety profile and high efficacy, mak­ing it possible to cure HCV infection in 90–95% of cases

Recurrence-associated chromosomal anomalies in meningiomas: Single-institution study and a systematic review with meta-analysis

•WHO grade II or III and loss of heterozygosity (LOH) on 1p, and 14q are responsible for recurrence of a sporadic meningioma.•WHO grading has greater impact on further tumour behaviour than molecular findings.•Sparse reporting of the rate of resection prevents full meta-analysing

The molecular pattern of histopathological progression to anaplastic meningioma – A case report

Meningiomas (MGs) are the most frequent primary tumours of the central nervous system (CNS) and exhibit a large spectrum of histological types and clinical phenotypes. The WHO classification of CNS tumours established strict diagnostic criteria of the benign (Grade 1), atypical (Grade 2) and anaplastic (Grade 3) subtypes. Combined with the resection rate, WHO grading has the most crucial role as the prognostic factor. Additionally, such biomarkers as Ki-67/MIB-1, progesterone receptors and phosphor-histone H3 were correlated with MG progression. Recently, it was suggested that the aggressive behaviour of some MGs is attributed to molecular alterations, regardless of their histopathology. The analysis of loss of heterozygosity (LOH) at chromosomes 1, 9, 10, 14 and 22 was performed. The presented case of WHO Grade 2 MG initially exhibited LOH at chromosomes 10, 14 and 22. In the first recurrence, the tumour genetic profiling revealed additional LOH at chromosome 1p and atypical histopathology. During the second recurrence, an aggressive phenotype was observed and tumour progressed to an anaplastic form. Considering the appearance of the tumour relapses, the set of molecular changes overtook the histopathological progression. The genetic and histopathological imbalance in the tumour progression in secondary anaplastic MGs has not been previously described. The evolution of genetic and histopathological changes was presented in the same patient. In the future, the individualised therapy of potentially more aggressive forms of MGs could be based on certain chromosome aberrations

Spektroskopia rezonansu magnetycznego w wewnątrzczaszkowych nowotworach pochodzenia glejowego

Background and purpose To determine in vivo magnetic resonance spectroscopy (MRS) characteristics of intracranial glial tumours and to assess MRS reliability in glioma grading and discrimination between different histopathological types of tumours. Material and methods Analysis of spectra of 26 patients with glioblastomas, 6 with fibrillary astrocytomas, 4 with anaplastic astrocytomas, 2 with pilocytic astrocytoma, 3 with oligodendrogliomas, 3 with anaplastic oligodendrogliomas and 17 control spectra taken from healthy hemispheres. Results All tumours’ metabolite ratios, except for Cho/Cr in fibrillary astrocytomas (p = 0.06), were statistically signiflcantly different from the control. The tumours showed decreased Naa and Cr contents and a high Cho signal. The Lac-Lip signal was high in grade III astrocytomas and glioblastomas. Reports that Cho/Cr ratio increases with glioma's grade whereas Naa/Cr decreases were not confirmed. Anaplastic astrocytomas compared to grade II astrocytomas had a statistically significantly greater ml/Cr ratio (p = 0.02). In pilocytic astrocytomas the Naa/Cr value (2.58 ± 0.39) was greater, whilst the Cho/Naa ratio was lower (2.14 ± 0.64) than in the other astrocytomas. The specific feature of oligodendrogliomas was the presence of glutamate/glutamine peak Glx. However, this peak was absent in two out of three anaplastic oligodendrogliomas. Characteristically, the latter tumours had a high Lac-Lip signal. Conclusions MRS in vivo cannot be used as a reliable method for glioma grading. The method is useful in discrimination between WHO grade I and WHO grade II astrocytomas as well as oligodendrogliomas from other gliomas.Wstęp i cel pracy Ustalenie charakterystyki spektroskopii magnetycznego rezonansu jądrowego (magnetic resonance spectroscopy – MRS) u chorych z nowotworami wewnątrzczaszkowymi pochodzenia glejowego oraz ocena przydatności tego badania w diagnostyce różnicowej typów histologicznych glejaków. Materiał i metody Przeprowadzono analizę widm MRS nowotworów u 26 chorych z glejakami wielopostaciowymi, 6 z gwiaździakami włókienkowymi, 4 z gwiaździakami anaplastycznymi, 2 z włosowatokomórkowymi, 3 ze skąpodrzewiakami, 3 ze skąpodrzewiakami anaplastycznymi oraz 17 widm kontrolnych pochodzących ze zdrowych półkul mózgu. Wyniki Wszystkie wskaźniki metaboliczne w przypadkach nowotworów, z wyjątkiem Cho/Cr w gwiaździakach włókienkowych (p = 0,06), różniły się znamiennie od tych w grupie kontrolnej. Nowotwory wykazywały zmniejszoną zawartość Naa i Cr oraz wysoki sygnał Cho. Sygnał Lac-Lip był wysoki w gwiaździakach III stopnia wg WHO i glejakach wielopostaciowych. Nie udało się potwierdzić doniesień, że wskaźnik Cho/Cr rośnie, a wskaźnik Naa/Cr maleje wraz ze wzrostem stopnia złośliwości glejaka. Gwiaździaki anaplastyczne wykazywały znamiennie wyższy wskaźnik ml/Cr (p = 0,02) w porównaniu z gwiaździakami II stopnia wg WHO. W gwiaździakach włosowatokomórkowych wartość Naa/Cr (2,58 ± 0,39) była większa, a Cho/Naa mniejsza (2,14 ± 0,64) niż w innych gwiaździakach. Skąpodrzewiaki charakteryzowała obecność szczytu glutaminianu/glutaminy (Glx), którego jednak nie obserwowano w 2 spośród 3 przypadków skąpodrzewiaków anaplastycznych. Dla tych ostatnich symptomatyczna była obecność silnego sygnału Lac-Lip. Wnioski Badanie MRS in vivo nie jest niezawodną metodą różnicującą glejaki wewnątrzczaszkowe. Wydaje się użyteczne w diagnostyce różnicowej gwiaździaków I i II stopnia wg WHO oraz w odróżnianiu skąpodrzewiaków od pozostałych glejaków

Low Content of Cyclosporine A and Its Metabolites in the Colostrum of Post-Transplant Mothers

The rate of post-transplant mothers who breastfeed while on immunosuppression is progressively increasing. Data on breastfeeding while on cyclosporine-based regimens are limited. Therefore, we assessed the amount of cyclosporine and its metabolites that might be ingested by a breastfed infant by measuring the concentration of cyclosporine and its metabolites in the colostrum of seven post-transplant mothers. The mean concentration of cyclosporine in the colostrum was 22.40 ± 9.43 mcg/L, and the estimated mean daily dose of the drug was 1049.22 ± 397.41 ng/kg/24 h. Only three metabolites (AM1, DHCsA, and THCsA) had mean colostrum amounts comparable to or higher than cyclosporine itself, with the daily doses being 468.51 ± 80.37, 2757.79 ± 1926.11, and 1044.76 ± 948.56 ng/kg/24 h, respectively. Our results indicate a low transfer of cyclosporine and its metabolites into the colostrum in the first two days postpartum and confirm the emerging change to the policy on breastfeeding among post-transplant mothers. A full assessment of the safety of immunosuppressant exposure via breastmilk will require further studies with long-term follow-ups of breastfed children

Effect of feeding on the pharmacokinetics of vilazodone in dogs

Vilazodone (VLZ) is a drug approved for the treatment of major depressive disorder in humans but no data are available for dogs. The present study aimed to evaluate the pharmacokinetics of a single oral 40 mg dose of VLZ in healthy Labrador dogs (n = 6) in fasted and fed conditions. Dogs were randomly divided in two (n = 3) groups in a cross-over study design (2 x 2). Group I was administered with VLZ at 40 mg/dog after fasting over-night. Group II was fed prior to and after administration of the same dose. A two-week wash-out period was observed. Plasma samples collected underwent LC-MS/MS analysis. VLZ concentrations were quantified in dogs' plasma in two different windows of time: 30 min to 10 h for the fasted group and 4 h to 35 h for the fed group. The values for t(1/2 lambda z) were statistically different between the groups (fed, 4.6 +/- 1.1 h vs fasted, 1.7 +/- 0.2 h). Tmax drastically changed between the groups (fed, 10 h vs fasted, 1.5 h), while C-max did not significantly vary (fed, 39.4 +/- 5.6 ng/mL vs fasted, 38.7 +/- 4.8 ng/mL). The AUC value was always statistically higher in the fed group. As a result, the average relative oral fasted bioavailability of VLZ was low, 28.8 +/- 6.1%. In conclusion, feeding can affect the pharmacokinetics of VLZ in the dog

The correlation of clinical and chromosomal alterations of benign meningiomas and their recurrences

Meningiomas (MGs) are the frequent benign intracranial tumors. Their complete removal does not always guarantee relapse-free survival. Recurrence-associated chromosomal anomalies in MGs haves been proposed as prognostic factors in addition to the World Health Organisation (WHO) grading, tumor size and resection rate. The aim of this study was to evaluate the frequency of deletions on chromosomes in sporadic MGs and to correlate them with the clinical findings and tumor behaviour. Along with survival, the tumor recurrence was the main endpoint. Chromosomal loss of heterozygosity (LOH) was studied. 46 benign MGs were subjected to the analysis, complete tumor resection was intended and no early mortalities were observed. Incomplete removal was related to parasagittal location and psammomatous hisptopathology (p<0.01). Chromosomal alterations were present in 82.6% of cases; LOH at 22q (67.4%) and 1p (34.8%) were the most frequent and associated with male sex (p=0.04). Molecular findings were not specific for any of the histopathologic grade. Tumor recurrence (14 of 46) correlated with tumor size (≥35mm), LOH at 1p, 14q, coexistence of LOH at 1p/14q, 10q/14q, ‘complex karyotype’ status (≥2 LOHs excluding 22q), patient age (younger <35), and Simpson grading of resection rate (≥3 of worse prognosis). The last 3 variables were independent significant prognostic factors in multivariate analysis and of the same importance in recurrence prediction (Receiver Operating Characteristic curves comparison p>0.05). Among the cases of recurrence, tumor progression was observed in 3 of 14. In 2 cases, LOH on 1p and/or coexistence of LOH 1p/14q correlated with anaplastic transformation

Cerebral venous and sinus thrombosis complicated by heparin-induced thrombocytopenia

Zakrzepica żył i zatok mózgu (CVT) jest rzadko występującą postacią żylnej choroby zakrzepowo- zatorowej, o rocznej zapadalności 2–4/1 000 000. Nowoczesne techniki obrazowania, przede wszystkim rezonans magnetyczny w połączeniu z flebografią rezonansu magnetycznego (MR-v) oraz flebografią tomografii komputerowej (CT-v), znacznie usprawniły proces diagnostyczny CVT. Niedawno opublikowane uzgodnieniowe zalecenia dotyczące postępowania w CVT rekomendują stosowanie terapeutycznych dawek heparyny niefrakcjonowanej (UFH) lub drobnocząsteczkowej (LMWH) w leczeniu wstępnym tej choroby oraz podawanie antagonistów witaminy K we wtórnej prewencji CVT. W pracy przedstawiono sposób leczenia pacjentki z CVT, u której w trakcie otrzymywania LMWH w dawkach terapeutycznych rozwinęła się małopłytkowość indukowana heparyną (HITT). W artykule podkreślono wagę właściwego monitorowania wstępnego leczenia heparyną oraz omówiono strategię leczenia HITT w Polsce, gdzie większość antykoagulantów zarejestrowanych do stosowania u pacjentów z HITT jest praktycznie niedostępna. Hematologia 2011; 2, 4: 363–369Cerebral venous and sinus thrombosis (CVT) is a rare form of venous thromboembolism, with annual incidence of 2–4 per million. Modern imaging techniques, particularly magnetic resonance imaging (MRI) combined with MR-venography and computed tomography venography (CT-v), have greatly improved the diagnosis of CVT. Recently published consensus-based guidelines on the treatment of CVT recommend therapeutic doses of unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) for the initial treatment of the disease followed by vitamin K antagonists for secondary CVT prevention. In this paper, we describe the management of patient with acute CVT who developed heparin induced thrombocytopenia thrombosis (HITT) while receiving therapeutic doses of LMWH. This report highlights the importance of careful monitoring of initial treatment with heparin, and discusses the strategy of HITT management in Poland, where most anticoagulants licensed for HITT treatment are virtually not achievable. Hematologia 2011; 2, 4: 363–36

Cerebrospinal fluid neurofilament light in suspected sporadic Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease. It is invariably fatal and displays a short clinical disease stage. The key event in sCJD is the propagation of a beta-sheet rich conformer of the physiological PrPC protein, known as PrPSc. Neuropathological disease characteristics include gliosis, neuronal loss and spongiform degeneration; disease clinical manifestations refer to mental and visual disabilities, cognitive impairment, gait or limb ataxia, myoclonus and mutism. Definite sCJD diagnosis requires post-mortem brain material histopathological examination. However, highly certain pre-mortem differential diagnosis is desired to exclude other treatable disorders and to reduce disease transmission risks. Detection and/or quantification of cerebrospinal fluid (CSF) biomarkers reflecting neuronal damage and PrPC misfolding in the diseased brain significantly enhance pre-mortem diagnosis. Previously established and newly identified biomarkers are used towards this direction. Increased CSF Neurofilament light chain (NFL) concentrations have been reported in several neurological disorders, including prion diseases. In the present study, we analyzed CSF NFL levels in two independent patient cohorts, consisting of highly suspected sCJD cases that were further classified as sCJD or non-CJD according to established diagnostic criteria. CSF NFL concentrations were increased in sCJD compared to non-CJD cases in both cohorts (area under the curve (with 95% confidence interval) equal to 0.89 (0.82 to 0.97) and 0.86 (0.77 to 0.96), respectively. CSF NFL was associated neither to age nor to sex but correlated with total-tau concentrations in both cohorts. Overall, our data provide independent validation of CSF NFL utility in sCJD differential diagnosis

Results from Polish Spondyloarthritis Initiative registry (PolSPI) : methodology and data from : the first year of observation

Objectives: Report on one-year results from the Polish Spondyloarthritis Initiative registry (PolSPI), containing the cross-sectional analysis of clinical and imaging data as well as database methodology. Material and methods: The PolSPI registry includes patients with axial (axSpA) and peripheral (per- SpA) spondyloarthritis according to ASAS classification criteria, and/or patients with ankylosing spondylitis according to modified New York criteria, psoriatic arthritis according to CASPAR criteria, arthropathy in inflammatory bowel disease, reactive arthritis, juvenile spondyloarthritis or undifferentiated spondyloarthritis. Epidemiologic data and history of signs, symptoms and treatment of spondyloarthritis are collected and assessment of disease activity is performed. Radiographic images of sacroiliac joint, cervical and lumbar spine, and results of bone densitometry are collected. Every 6 months blood samples for inflammatory markers, and for long-term storage are taken. Results: During a one-year period from September 2015 to August 2016, 63 patients were registered on an electronic database; 44 (69.8%) of patients were classified as axial spondyloarthritis (axSpA) and 19 (30.2%) as peripheral spondyloarthritis (perSpA) according to ASAS criteria. Statistically significant differences between axSpA and perSpA were discovered in the percentage of HLA-B27 antigen occurrence (92.6% and 50%, respectively), BASDAI (2.8% and 4.1%, respectively), DAS 28 (2.66% and 4.03%, respectively), percentage of peripheral arthritis (20% and 88.8%, respectively), enthesitis (26.7% and 70.6%, respectively), dactylitis (6.7% and 88.9%, respectively), as well as extra-articular symptoms: acute anterior uveitis (26.7% and 5.6% , respectively) and psoriasis (6.9% and 55.6%, respectively). Patients with axSpA had significantly higher mean grade of sacroiliac involvement according to New York criteria, higher mSASSS score, and lower T-score in femoral neck in bone densitometry. Conclusions: At the early stage of the disease patients with axSpA compared to those with perSpA, have more advanced structural damage of sacroiliac joints and spine, and lower bone mineral density in the femoral neck. In the upcoming years the PolSPI registry will prospectively follow-up patients with SpA, recording response to treatment and carrying out research on interaction of inflammation and bone remodelling