Krzysztof Małyszczak

Physical and psychological impairments of women with upper limb lymphedema following breast cancer treatment

Objective: The aim of the study was to identify factors associated with worse physical and emotional functioning of breast cancer survivors with upper extremity lymphedema.

Evaluation of early cerebral metabolic, perfusion and microstructural changes in HCV-positive patients: a pilot study.

BACKGROUND & AIMS The aim of the study was to evaluate early metabolic perfusion, and microstructural cerebral changes in patients with the hepatitis C virus (HCV) infection and normal appearing brain on plain MR using advanced MR techniques, as well as to assess correlations of MR measurements with the liver histology activity index (HAI). METHODS Fifteen HCV-positive patients and 18 control subjects underwent single voxel MR spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI), using a 1.5T MR unit. MRS metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr) were calculated. PWI values of relative cerebral blood volume (rCBV) were assessed from 8 areas including several cortical locations, basal ganglia, and fronto-parietal white matter. DTI fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from 14 white matter tracts. RESULTS Compared to controls, HCV-positive patients showed significantly (p < 0.05) lower NAA/Cr ratios within frontal and parietal white matters, lower rCBV values within frontal and temporo-parietal cortices, decreased FA values, as well as increased ADC values in several white matter tracts. We also found elevated rCBV values in basal ganglia regions. The increase in mI/Cr and Cho/Cr ratio was correlated with a higher HAI score. CONCLUSIONS The results of advanced MR techniques indicate neurotoxicity of HCV reflected by neuronal impairment within white matter, cortical hypoperfusion, and disintegrity within several white matter tracts. Hyperperfusion in basal ganglia may be an indicator of brain inflammation in HCV patients. Our findings may suggest a biologic link between HCV-related liver disease and cerebral dysfunction.

Value of Perfusion-Weighted MR Imaging in the Assessment of Early Cerebral Alterations in Neurologically Asymptomatic HIV-1-Positive and HCV-Positive Patients

Background and Purpose Asymptomatic central nervous system (CNS) involvement occurs in the early stage of the human immunodeficiency virus (HIV) infection. It has been documented that the hepatitis C virus (HCV) can replicate in the CNS. The aim of the study was to evaluate early disturbances in cerebral microcirculation using magnetic resonance (MR) perfusion-weighted imaging (PWI) in asymptomatic HIV-1-positive and HCV-positive patients, as well as to assess the correlation between PWI measurements and the clinical data. Materials and Methods Fifty-six patients: 17 HIV-1-positive non-treated, 18 HIV-1-positive treated with combination antiretroviral therapy (cART), 7 HIV-1/HCV-positive non-treated, 14 HCV-positive before antiviral therapy and 18 control subjects were enrolled in the study. PWI was performed with a 1.5T MR unit using dynamic susceptibility contrast (DSC) method. Cerebral blood volume (CBV) measurements relative to cerebellum (rCBV) were evaluated in the posterior cingulated region (PCG), basal ganglia (BG), temporoparietal (TPC) and frontal cortices (FC), as well as in white matter of frontoparietal areas. Correlations of rCBV values with immunologic data and liver histology activity index (HAI) were analyzed. Results Significantly lower rCBV values were found in the right TPC and left FC as well as in PCG in HIV-1-positive naïve (p = 0.009; p = 0.020; p = 0.012), HIV-1 cART treated (p = 0.007; p = 0.009; p = 0.033), HIV-1/HCV-positive (p = 0.007; p = 0.027; p = 0.045) and HCV-positive patients (p = 0.010; p = 0.005; p = 0.045) compared to controls. HIV-1-positive cART treated and HIV-1/HCV-positive patients demonstrated lower rCBV values in the right FC (p = 0.009; p = 0.032, respectively) and the left TPC (p = 0.036; p = 0.005, respectively), while HCV-positive subjects revealed lower rCBV values in the left TPC region (p = 0.003). We found significantly elevated rCBV values in BG in HCV-positive patients (p = 0.0002; p<0.0001) compared to controls as well as to all HIV-1-positive subjects. There were no significant correlations of rCBV values and CD4 T cell count or HAI score. Conclusions PWI examination enables the assessment of HIV-related as well as HCV-related early cerebral dysfunction in asymptomatic subjects. HCV-infected patients seem to reveal the most pronounced perfusion changes.

Depression and neuroticism in patients with chronic hepatitis C: Correlation with peripheral blood mononuclear cells activation

BACKGROUND Hepatitis C virus (HCV) infection is commonly associated with cognitive dysfunction and depression, which could be related to direct brain infection. Viral sequences and proteins were found in brain macrophage/microglia cells and these cells were reported to be activated. Since blood leukocytes cross blood-brain barrier, activation state of peripheral blood mononuclear cells (PBMC) could reflect the state of brain immune cells. OBJECTIVE The aim of the study was to determine whether depression and neuroticism in chronic HCV infection correlates with the expression of key cytokines and chemokines in PBMC. DESIGN We studied 24 HCV-positive patients undergoing treatment with interferon and ribavirin. Patients were tested for depression using Beck Depression Inventory (BDI) and Montgomery Åsberg Depression Rating Scale (MADRS), while neuroticism was assessed by the Revised Eysenck Personality Inventory (N/EPO-R). Transcripts representing 28 various cytokines and chemokines were measured by real-time quantitative PCR in PBMC. RESULTS Prior to therapy BDI and MADRS positively correlated with viral load while neuroticism correlated with IL-3, IL-8 and M-CSF transcription levels. Six months after therapy there was positive correlation between depression and/or neuroticism scores and the levels of proinflammatory cytokines TNF-α and IL-12 transcripts, as well as IL-8, IL-10, IL-16, MCP-1, MCP-2, MIP-1-alpha, MIP-1-beta, and TGF-beta, and IFN-β transcripts. CONCLUSION Activation of PBMC, as measured by the level of cytokine and chemokine transcripts, correlates with depression and neuroticism scores. These findings suggest a pivotal role of immune cells activation in depression and possibly neurocognitive dysfunction among chronic hepatitis C patients.

Replication of hepatitis C virus in peripheral blood mononuclear cells in patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin.

INTRODUCTION Hepatitis C virus (HCV) is a primarily hepatotropic virus, but hepatocytes are not the only localization of its replication. It is still unclear if extrahepatic HCV replication, measured as the detection of HCV RNA negative strand in peripheral blood mononuclear cells (PBMCs) before initiation of treatment, has an influence on therapy response. Detection of HCV RNA in extrahepatic sites for assessment of therapy efficacy is not routinely used in clinical practice. The aim of the study was to evaluate whether the replication of HCV in PBMCs affects the rate of sustained virological response (SVR). MATERIALS AND METHODS The study group comprised 55 patients with chronic hepatitis C, originally treatment naive. They were treated with pegylated interferon (PEG-IFN) alpha 2a and ribavirin, with the standard dosing schedule. Parallel serum samples for HCV RNA and PBMC samples for HCV RNA negative strand were obtained at baseline, at the end of treatment and 24 weeks after finishing therapy. RESULTS Undetectable HCV RNA in serum at the end of therapy was found in 48 patients (87.3%), while 33 patients (60.0%) achieved sustained virological response (SVR) (51% for HCV genotype 1 and 78% for genotype 3, respectively). Fifteen individuals (31.3%) were relapsers. Factors associated with significantly higher rate of SVR were young age, mild or no fibrosis and infection with HCV genotype 3. HCV RNA negative strand in PBMCs before treatment was found in 21.8% (12 out of 55 patients). HCV RNA negative strand was detected at baseline more frequently in patients who later achieved SVR. Relapse appeared significantly more often in patients with negative strand at the end of therapy: in 2 out of 15 individuals compared to 0 out of 33 patients (p=0.03). CONCLUSIONS Presence of negative HCV RNA strand in PBMCs before treatment may be suggested as a potential marker of good treatment response. Detection of negative strand at the end of therapy is a predictor of relapse.

Analysis of Serum of Patients With Alzheimer’s Disease for the Level of Advanced Glycation End Products

Data on the serum level of advanced glycation end products (AGEs) in Alzheimer’s disease (AD) patients are scarce, although a specific biochemical marker easy to detect in body fluids is desired for an early diagnosis of disease and to monitor the effects of therapeutic treatment. In the current study, the content of AGEs was examined with an immunochemical assay in the sera of AD patients, in the frame of a search for a biochemical marker of disease. Subjects with AD and vascular dementia (VaD) were included in the study (n = 30; age range, 68-70 years). The results were compared to the healthy control groups. The enzyme-linked immunosorbent assay (ELISA) inhibition test for the determination of AGEs is based on a rabbit anti-AGE, affinity-purified antibody and a model AGE-myoglobin antigen, in which a serum sample treated with proteinase K is used as an inhibitor. For the measurement of immune complexes and anti-AGE antibodies, the corresponding ELISA tests have been applied. The AGE level in the VaD group (49.5 UAGE) was higher than in AD patients (46.1 UAGE). The level of total AGEs in the sera of AD patients was significantly lower than in the control group (50/51.6 UAGE). These relations were not observed with regard to the immune complexes and anti-AGE antibody levels in AD (70.2 UIC/0.027 UIgG) and VaD (83 UIC/0.034 UIgG) patients because the levels of these parameters were similar to the controls (76.2 UIC/0.042 UIgG). The work revealed the lower level of circulating serum AGEs in patients with AD in relation to healthy controls.

Co-Infection of the Hepatitis C Virus With Other Blood-Borne and Hepatotropic Viruses Among Hemophilia Patients in Poland

Background The prevalence of HCV infection in people with hemophilia is substantially higher than that in the general population (63% - 98%). Multiple transfusions and substitutive therapy have also been linked to a high risk of HBV and HIV transmission. However, the prevalence of other blood-borne viral infections in this population is less well known. Objectives This study aimed to assess the prevalence of co-infection with HBV and other blood-borne viruses in Polish HCV-infected hemophiliacs. Methods Seventy-one individuals, the majority of whom were male (94.36%), who had congenital bleeding disorders (60 had hemophilia A, five had hemophilia B, and six had other factor deficiencies) and HCV infection, which was defined as the presence of positive anti-HCV antibodies, were included in this study. The study group was divided into two subgroups according to the year in which blood donors were first tested for HBsAg in Poland. The serological markers were screened using commercially available enzyme immunoassays according to the manufacturer’s instructions. The molecular tests were performed using real-time PCR technology with commercial assays according to the manufacturer’s instructions. Results The spontaneous elimination rate of HCV RNA was 29.6%. The HCV genotype 1 was detected in 28 patients (65.1%), genotype 2 in one patient (2.3%), genotype 3 in 11 patients (25.6%), genotype 4 in two patients (4.7%), and a mixed infection with genotypes 1 and 4 was detected in one person (2.3%). Fifty-three patients (74.6%) were anti-HBc positive. Among the seven HBsAg(+) patients, three individuals were HBV-DNA positive. No occult hepatitis B was detected. In six HBsAg positive patients, the HCV RNA was positive, while one patient was also infected with HIV. The prevalence rate of past infection with HAV in the study group was 30.9%, with a tendency for a higher prevalence in older patients. The prevalence of CMV and EBV infection was high and similar to that seen in the general population. All the patients were HGV and HTLV-1 negative. Conclusions The diagnostics and management of infections with hepatotropic viruses, particularly HBV, are neglected in hemophilic patients. All patients with coagulation disorders and a history of exposure to non-inactivated blood products should be screened for blood-borne infections. The prevalence of other potentially blood-borne viral infections exhibited a pattern similar to that observed in the general population.

Distress and functioning in mixed anxiety and depressive disorder.

Abstract  The aim of the present study was to evaluate the validity of mixed anxiety and depressive disorder (MADD) with reference to functional characteristics and symptomatic characteristics in comparison with anxiety disorders, depressive disorders, and groups showing subthreshold symptoms (exclusively depressive or anxiety related). The present study was carried out in the following three medical settings: two psychiatric and one primary care. Patients seeking care in psychiatric institutions due to anxiety and depressive symptoms and attending primary medical settings for any reason were taken into account. A total of 104 patients (65 women and 39 men, mean age 41.1 years) were given a General Health Questionnaire (GHQ‐30), Global Assessment of Functioning (GAF) and Present State Examination questionnaire, a part of Schedules for Clinical Assessment in Neuropsychiatry, Version 2.0. There were no statistically relevant differences between MADD and anxiety disorders in median GHQ score (19 vs 16) and median GAF score (median 68.5 vs 65). When considering depressive disorders the median GHQ score (28) was higher, and median GAF score (59) was lower than that in MADD. In groups with separated subthreshold anxiety or depressive symptoms, median GHQ scores (12) were lower and median GAF scores (75) were higher than that in MADD. The most frequent symptoms of MADD are symptoms of generalized anxiety disorder (GAD) and depression. Mixed anxiety and depressive disorder differs significantly from GAD only in higher rates of depressed mood and lower rates of somatic anxiety symptoms. Distinction from depression was clearer; six of 10 depressive symptoms are more minor in severity in MADD than in the case of depression. Distress and interference with personal functions in MADD are similar to that of other anxiety disorders. A pattern of MADD symptoms locates this disorder between depression and GAD.

Stage of liver fibrosis in patients with congenital bleeding disorders and infected with hepatitis C virus

INTRODUCTION Hepatitis C virus (HCV) is the major cause of chronic liver disease in patients with hemophilia. However, since liver biopsy should not be routinely used in these patients, the accurate assessment of the stage of fibrosis has been limited so far. OBJECTIVES The aim of this study was to determine the stage of liver fibrosis in HCV‑infected patients with hemophilia by using noninvasive methods of fibrosis assessment, and to analyze the influence of risk factors on liver fibrosis. PATIENTS AND METHODS The study included 71 HCV‑infected patients with hemophilia and other congenital bleeding disorders. Patients were divided into 3 groups: HCV-RNA negative after successful treatment, HCV-RNA negative after spontaneous elimination of infection, and HCV‑RNA positive. Liver fibrosis was measured with shear wave elastography and FibroTest. The risk factors for liver fibrosis were analyzed, including demographic factors, HCV genotype, coinfections, and comorbidities. RESULTS Cirrhosis or significant fibrosis (METAVIR score >F2) was observed in 26.8% of the patients. The stage of fibrosis was associated with age and estimated duration of infection (P <0.001). Active and past HBV infection did not affect fibrosis. The stage of liver fibrosis was lower in patients with spontaneous clearance of HCV (P = 0.007). CONCLUSIONS Patients in our study had a similar stage of liver fibrosis to that reported by other studies on hemophilia. The older age and long duration of infection are the main risk factors for advanced fibrosis. Noninvasive methods such as shear wave elastography and FibroTest may allow a proper assessment of the fibrosis stage in hemophilia patients, particularly when used together and in correlation with other clinical parameters. They may also be useful in other groups of HCV‑infected patients.

Mixed anxiety and depressive disorder before and after psychodynamic group psychotherapy: a 1-year follow-up study.

Abstract Objective. The aim of our study was to observe the outcome of MADD in comparison with depressive (DD) and anxiety (AD) disorders. Method. Patients treated with 12 weeks of group psychodynamic psychotherapy in a psychiatric day care ward were examined using SCAN 2.1 at admission and 1 year after admission. Treatment was indicated on the basis of diagnosis of ICD-10 – F4–F6. A total of 139 patients were included, 110 (79.1%) of whom were examined at the follow-up point. Results. The prevalence of MADD increased from 22.7% at the baseline to 33.6% at the end. The outcome of MADD was statistically different from the outcome of DD (χ2=18.4, P=0.0025), but not different from the outcome of comorbid DD and AD (χ2=1.8, P=0.84), nor generalized anxiety disorder (χ2=8.1, P=0.15), nor other AD (χ2=5.3, P=0.38). Conclusion. MADD is a useful diagnosis of a transitional or residual form of comorbid DD and AD in some specific population groups. A diagnosis of personality disorder can sustain long-term diagnosis of MADD.