Predicting risk factors for thromboembolic complications in patients with sickle cell anaemia - lessons learned for prophylaxis.

OBJECTIVE: To assess the clinical and laboratory predictors of venous thromboembolism (VTE) in patients with sickle cell anaemia (SCA) and its relationship to morbidity and mortality. METHODS: This retrospective case-control study analysed data from patients with SCA that experienced VTE compared with matched control patients with SCA but no VTE (2:1 ratio). RESULTS: A total of 102 patients with SCA were enrolled (68 cases with VTE and 34 controls). Amongst the 68 cases (median age, 29.5 years), 26 (38.2%) presented with isolated pulmonary embolism (PE). A higher prevalence of splenectomy (73.5% versus 35.3%) was observed in the cases compared with the controls. A significantly higher prevalence of central venous catheter (CVC) insertion (42.6% versus 8.8%) was observed in the cases compared with the controls. High white blood cell counts, serum lactic dehydrogenase (LDH), bilirubin and C-reactive protein (CRP) and low haemoglobin (Hb) and HbF were significant risk factors for VTE. Forty-two cases (61.8%) developed acute chest syndrome, 10 (14.7%) had a stroke and seven (10.3%) died. CONCLUSIONS: VTE in patients with SCA has a high impact on morbidity and mortality. PE was the leading presentation of VTE, with CVC insertion, high LDH, bilirubin, CRP and white blood cell counts along with low Hb and HbF constituting other significant risk factors.

Formulation and In Vitro Evaluation of Pellets Containing Sulfasalazine and Caffeine to Verify Ileo-Colonic Drug Delivery.

The ColoPulse coating is a pH-dependent coating that can be used to target drug release to the ileo-colonic region. ColoPulse coated tablets and capsules have demonstrated their targeting capabilities in vivo in more than 100 volunteers and patients. However, so far the ColoPulse coating has not been used for multi-particulate pellet formulations. The sulfasalazine-caffeine method can be used to confirm ileo-colonic drug delivery in vivo. Caffeine serves as a release marker in this method, while sulfasalazine serves as a marker for colonic arrival. In this study, extrusion-spheronization was used to produce microcrystalline cellulose based pellets containing both caffeine and sulfasalazine. Dissolution tests revealed that a superdisintegrant, i.e., croscarmellose sodium or sodium starch glycolate, should be incorporated in the formulation to achieve acceptable release profiles for both sulfasalazine and caffeine. However, acceptable release profiles were only obtained when the pelletizing liquid consisted of ethanol/water 1/1 (v/v) but not with pure water. This phenomenon was ascribed to the differences in the degree of swelling of the superdisintegrant in the pelletizing liquid during the granulation process. The pellets were coated with the ColoPulse coating and showed the desired pH-dependent pulsatile release profile in vitro. In future clinical studies, ileo-colonic targeting should be verified.

Self-esteem and other risk factors for depressive symptoms among adolescents in United Arab Emirates.

BACKGROUND: Little is known about depressive symptoms among adolescents in the United Arab Emirates (UAE). This study aimed to identify the prevalence of depression and its association with self-esteem, individual, parental and family factors among adolescents aged 12 to 18 in UAE. METHODS: Six hundred adolescents, aged 12 to 18 years were recruited from 4 of 111 schools in a cross-sectional study. We administered Beck Depression Inventory Scale and Rosenberg Self-esteem Scale to measure self-report symptoms of depression and self-esteem. We used multiple linear regression to identify significant predictors of depression. RESULTS: Over 86% of the identified sample participated to the survey. The mean age of the sample was 14.3 (±1.3) with an excess of girls (61%). Depressive symptoms were detected in 17.2% (95% CI 14.2-20.7). There was an inverse relationship between self-esteem scores and depressive symptoms. Positive predictors of depressive symptoms, having controlled for age, gender, and ethnicity included experiencing neglect, being verbally abused in school, having no monthly allowance to spend in school, a history of physical morbidities requiring treatment, being a current or past smoker and a low family income. CONCLUSION: The high prevalence of depressive symptoms measured in this survey suggests a significant public health problem among adolescents in the UAE. Public health interventions aimed at facilitating education and early detection and potential treatment of depressive symptoms are a priority in the region.

Recall of physiology knowledge among medical interns: an exploratory study in Riyadh, Saudi Arabia.

The aim of the study was to explore the factors associated with the recall of basic medical physiology knowledge among medical interns and to determine the level of retained basic science knowledge. Two hundred and four interns, 114 women and 90 men, working in two major tertiary medical care centers, King Fahad Medical City (KFMC; 29 students) and King Khalid University Hospital (KKUH; 117 students), in Riyadh city, participated in the study. An anonymous knowledge test with 10 validated multiple-choice questions was developed specifically for this purpose. One hundred and forty-six interns (117 working at KKUH and 29 at KFMC) had graduated from medical schools adopting a conventional instructional system, whereas 58 (3 from KKUH and 55 from KFMC had graduated from schools adopting an integrated system (hybrid problem-based learning). Fifty-two students (26%) gained a score ≥60%, whereas 152 students (74%) obtained <60% of the score. Higher scores were associated with younger age ( P < 0.01), traditional curriculum ( P < 0.001), interns from KKUH ( P < 0.001), and candidates for postgraduate studies ( P < 0.02). There was no significant association between recall of physiology knowledge and all other variables studied, including sex. Multivariate analyses show that age and traditional curriculum are the only significant predictors of knowledge retention. Almost three-fourths of the interns scored <60%, and higher scores were significantly associated with younger interns, traditional curriculum, working in KKUH, and interns preparing for graduate studies. However, the difference between the two curricula disappears when the influence of hospital training is considered.

Secondary HLH Case Report Highlighting Clinical Challenges.

A 19-year-old patient with relapsed acute myeloid leukemia (AML) developed severe and prolonged cytopenia and unexplained jaundice and fever after salvage chemotherapy. His workup revealed hemophagocytosis on the bone marrow biopsy. He was treated for HLH (hemophagocytic lymphohistiocytosis) secondary to AML and chemotherapy. The patient died on day 56 after starting his salvage chemotherapy. Unexpectedly, after his death, the microbiology laboratory reported positive mycobacterial growth from a bronchoalveolar lavage (BAL) sample taken during the workup of his fever. This case illustrates the difficulties in the diagnostic workup of HLH to identify triggers in a timely manner so that a targeted and specific therapy can be administered quickly, given the rapid and deadly evolution of the HLH process.

Management of cancer-associated upper extremity deep vein thrombosis with and without venous catheters at a tertiary care center.

INTRODUCTION: Data on management of upper extremity deep vein thrombosis (UEDVT) in patients with cancer is limited. The objective of this study was to determine risk factors for UEDVT and the rates of recurrence and bleeding in a real-world setting. METHODS: Retrospective review of consecutive patients assessed for cancer-associated UEDVT. Outcome measures were recurrent venous thromboembolism (VTE), and major and clinically relevant non-major bleeding (CRNMB). Risk factors for recurrent VTE and bleeding were assessed. RESULTS: Mean duration of follow-up was 7.2 months. Two hundred cases were identified; 69% were associated with a central line. Non-line associated UEDVT occurred more frequently in the setting of breast cancer, lung cancer and documented local mass effect. The incidence of recurrent VTE was 18.5%, of which 14 (37.8%) were ipsilateral UEDVT. The risk of recurrence is higher with male gender (HR 2.0, 95% CI; 1.0-4.0). Major and CRNMB occurred in 1% and 11.5%, respectively. Concurrent use of an antiplatelet agent was associated with a higher risk of CRNMB compared to anticoagulant therapy alone (HR 3.9, 95% CI; 1.4-10.7). CONCLUSIONS: Presence of a venous catheter was the primary risk factor for UEDVT, however, extrinsic compression by local tumour may be just as important for some cancer types. Furthermore, the majority of recurrent events did not occur in the same upper limb suggesting that UEDVT may be predictive of increased thrombotic risk rather than just a local effect of catheters.

Prognostic role of KIR genes and HLA-C after hematopoietic stem cell transplantation in a patient cohort with acute myeloid leukemia from a consanguineous community.

NK cell activity is tuned by a balance of activating and inhibitory signals transmitted via their respective receptors, including killer immunoglobulin-like receptors (KIRs). The impact of NK cells on graft-versus-leukemia following hematopoietic stem cell transplantation (HSCT) is well established. These effects sometimes lead to GvHD. The link between KIR/HLA interaction and GvHD remains unclear. Herein, we studied the impact of the KIR/HLA interaction on HSCT outcomes in a longitudinal follow-up study of a highly consanguineous HLA-matched related cohort. Peripheral blood DNA was collected from HSCT donor-recipient pairs (n = 87), including 41 AML pairs. KIR and HLA were genotyped and significant results were only measured when matching KIR (donor) with HLA (recipients). GvHD was observed in 47% of patients. KIR2DL1_C2 and 2DS2_C1 (P = 0.02 and 0.04, respectively) matching was associated with an increased incidence of acute GvHD in AML donor-recipient pairs. The rate of chronic GvHD also rose in AML patients who were matched for KIR2DS1_C2 (P = 0.004) and had either KIR2DL2 or KIR2DS2 (P = 0.03). In conclusion, matching of KIR2DL1, 2DS1, and 2DS2 in donors with their HLA-C ligands in recipients is associated with increased GvHD, and holds potential for selection of HSCT donors.

Spectrum of bone marrow pathology and hematological abnormalities in methylmalonic acidemia.

Patients with isolated methylmalonic acidemia (MMA) may present with a wide range of hematological complications including anemia, leukopenia, thrombocytopenia, and pancytopenia. However, there are very limited data on the development of hemophagocytosis or myelodysplasia in these patients. We report three patients with isolated MUT related MMA who presented with severe refractory pancytopenia during acute illness. Their bone marrow examination revealed a wide spectrum of pathology varying from bone marrow hypoplasia, hemophagocytosis to myelodysplasia with ring sideroblasts. We discuss their management and outcome. This report emphasizes the need for bone marrow examination in these patients with refractory or unexplained severe cytopenia, to confirm bone marrow pathology, and to rule out other diseases with similar clinical presentation for a better clinical outcome.

Genetic non-discrimination policy in Canada: Assessing windows of opportunity for policy change.

As the ease of obtaining genetic information for both the diagnosis and treatment of diseases has become increasingly common, so have concerns about the misuse of such information. The obstacles Canada faces in adopting genetic non-discrimination legislation have left health leaders with a lack of clear direction. Using the Kingdon agenda-setting framework, this article will identify lost opportunities for policy change and will analyze the potential for the adoption of a genetic non-discrimination policy in Canada. Windows of opportunity for policy change have existed in the past, but these windows have closed prior to a policy being adopted. More recently, the alignment of problem, policy, and politics streams in the agenda-setting process has resulted in a new window of opportunity. The adoption of a clear and coherent policy will provide the public with protection and health leaders with greater direction around genetic information.

Thalassemia Major: Transplantation or Transfusion and Chelation.

Thalassemia is the most common monogenic hematologic disease that affects millions in the world and kills thousands of patients every year. Without transfusion or transplantation, patients with thalassemia major are expected to die within months of diagnosis. However, long-term transfusion and chelation therapy is highly challenging for many developing countries where the disease is prevalent, representing a major and unsustainable health burden. Stem cell transplantation is the only cure for thalassemia. It has witnessed major developments that have made it less toxic, more successful, and feasible for a larger number of patients with diverse comorbidities and from a wider range of donors. Advances in human leukocyte antigen typing have greatly refined alternate donor selection with results of matched unrelated donors similar to matched sibling donors. Novel strategies such as haploidentical and cord blood transplantation have increased the possibility of patients with no healthy donor to get a better opportunity to survive and avoid chronic transfusion complications. Cost-effectively, transplantation should be considered the primary treatment of choice in the presence of a suitable related or unrelated donor and at centers with a satisfactory experience in the field of transplantation and particularly, in managing those with thalassemia. Despite some complications such as graft-versus-host disease and late conditioning effects, the overall improvement in the quality of life of thalassemia is difficult to deny. Unfortunately, the number of transplants for thalassemia represents only a minority of all transplants conducted globally and the essential requirement for transplants for thalassemia in limited-resources countries should mandate the transplant societies, including Worldwide Network for Blood and Marrow Transplantation, to collaborate to help initiate and support specialized transfusion and transplant programs for managing thalassemia.

Outcomes of low-molecular-weight heparin treatment for venous thromboembolism in patients with primary and metastatic brain tumours.

Venous thromboembolism (VTE) is one of the most common complications in patients with brain tumours. There is limited data available in the literature on VTE treatment in these patients. We conducted a matched retrospective cohort study of patients with primary or metastatic brain cancer who were diagnosed with cancer-associated VTE. Patients were selected after a retrospective chart review of consecutive patients who were diagnosed with cancer-associated VTE between January 2010 and January 2014 at the Juravinski Thrombosis Clinic, Hamilton, Canada. Controls were age- and gender-matched patients with cancer-associated VTE from the same cohort, but without known brain tumours. A total of 364 patients with cancer-associated VTE were included (182 with primary or metastatic brain tumours and 182 controls). The median follow-up duration was 6.7 (interquartile range 2.5-15.8) months. The incidence rate of recurrent VTE was 11.0 per 100 patient-years (95 % CI; 6.7-17.9) in patients with brain tumours and 13.5 per 100 patient-years (95 % CI; 9.3-19.7) in non-brain tumour group. The incidence of major bleeding was 8.6 per 100 (95 % CI; 4.8-14.7) patient-years in patients with brain tumours versus 5.0 per 100 patient-years (95 % CI; 2.8-9.2) in controls. Rate of intracranial bleeding was higher in brain tumour patients (4.4 % vs 0 %, p-value=0.004). In summary, rates of recurrent VTE and major bleeding were not significantly different in patients with cancer-associated VTE in the setting of primary or metastatic brain tumours compared those without known brain tumours. However, greater numbers of intracranial bleeds were observed in patients with brain tumours.

Protein signatures as potential surrogate biomarkers for stratification and prediction of treatment response in chronic myeloid leukemia patients.

There is unmet need for prediction of treatment response for chronic myeloid leukemia (CML) patients. The present study aims to identify disease-specific/disease-associated protein biomarkers detectable in bone marrow and peripheral blood for objective prediction of individual's best treatment options and prognostic monitoring of CML patients. Bone marrow plasma (BMP) and peripheral blood plasma (PBP) samples from newly-diagnosed chronic-phase CML patients were subjected to expression-proteomics using quantitative two-dimensional gel electrophoresis (2-DE) and label-free liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of 2-DE protein fingerprints preceding therapy commencement accurately predicts 13 individuals that achieved major molecular response (MMR) at 6 months from 12 subjects without MMR (No-MMR). Results were independently validated using LC-MS/MS analysis of BMP and PBP from patients that have more than 24 months followed-up. One hundred and sixty-four and 138 proteins with significant differential expression profiles were identified from PBP and BMP, respectively and only 54 proteins overlap between the two datasets. The protein panels also discriminates accurately patients that stay on imatinib treatment from patients ultimately needing alternative treatment. Among the identified proteins are TYRO3, a member of TAM family of receptor tyrosine kinases (RTKs), the S100A8, and MYC and all of which have been implicated in CML. Our findings indicate analyses of a panel of protein signatures is capable of objective prediction of molecular response and therapy choice for CML patients at diagnosis as 'personalized-medicine-model'.

Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies.

Background. We studied DNA chimerism in cell-free DNA (cfDNA) in patients treated with HSCT. Methods. Chimerism analysis was performed on CD3+ cells, polymorphonuclear (PMN) cells, and cfDNA using 16 small tandem repeat loci. The resulting labeled PCR-products were size-fractionated and quantified. Results. Analyzing samples from 191 patients treated with HSCT for nonneoplastic hematologic disorders demonstrated that the cfDNA chimerism is comparable to that seen in PMN cells. Analyzing leukemia patients (N = 126) showed that, of 84 patients with 100% donor DNA in PMN, 16 (19%) had evidence of clinical relapse and >10% recipient DNA in the plasma. Additional 16 patients of the 84 (19%) showed >10% recipient DNA in plasma, but without evidence of relapse. Eight patients had mixed chimerism in granulocytes, lymphocytes, and plasma, but three of these patients had >10% recipient DNA in plasma compared to PMN cells and these three patients had clinical evidence of relapse. The remaining 34 patients showed 100% donor DNA in both PMN and lymphocytes, but cfDNA showed various levels of chimerism. Of these patients 14 (41%) showed laboratory or clinical evidence of relapse and all had >10% recipient DNA in cfDNA. Conclusion. Monitoring patients after HSCT using cfDNA might be more reliable than cellular DNA in predicting early relapse.

Serum Total Bilirubin, not Cholelithiasis, is Influenced by UGT1A1 Polymorphism, Alpha Thalassemia and ß(s) Haplotype: First Report on Comparison between Arab-Indian and African ß(s) Genes.

BACKGROUND: We explored the potential relationship between steady state serum bilirubin levels and the incidence of cholelithiasis in the context of UGT1A1 gene A(TA)nTAA promoter polymorphism in Omani sickle cell anemia (SCA) patients, homozygotes for African (Benin and Bantu) and Arab-Indian ß(S) haplotypes, but sharing the same microgeographical environment and comparable life style factors. METHODS: 136 SCA patients were retrospectively studied in whom imaging data including abdominal CT scan, MRI or Ultrasonography were routinely available. Available data on the mean steady state hematological/biochemical parameters (n=136), ß(s) haplotypes(n=136), α globin gene status (n=105) and UGT1A1 genotypes (n=133) were reviewed from the respective medical records. RESULTS: The mean serum total bilirubin level was significantly higher in the homozygous UGT1A1(AT)7 group as compared to UGT1A1(AT)6 group. Thus, not cholelithiasis but total serum bilirubin was influenced by UGT1A1 polymorphism in this SCA cohort. CONCLUSION: As observed in other population groups, the UGT1A1 (AT)7 homozygosity was significantly associated with raised serum total bilirubin level, but the prevalence of gallstones in the Omani SCA patients was not associated with α thalassaemia, UGT1A1 polymorphism, or ß(s) haplotypes.

Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD) over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX) for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m(2) seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR) in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR) in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals.

Allogeneic hematopoietic stem cell transplantation in adolescent and adult patients with high-risk T cell acute lymphoblastic leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is often recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (≥CR2) and sometimes in high-risk (HR) patients in first complete remission (CR1). Between January 1995 and July 2009, 53 patients with HR T-ALL underwent allo-SCT at our institution. Median age was 18 years (range, 14-51). Thirty-two patients (60.3%) were in CR1, 18 (34%) were in ≥CR2, and 3 (5.7%) were in relapse. The cumulative incidence of nonrelapse mortality at 5 years was 22.5%. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 40.2%, and that of chronic GVHD was 43.7%. The majority of relapses (88.9%) occurred within 1 year after SCT. The cumulative incidence of relapse (CIR) at 5 years was 35.6%. CIR was 29.8% in patients in CR1, 35.3% in patients in ≥CR2 and all patients transplanted in relapse had disease recurrence post-allo-SCT (P = .000). Overall survival (OS) and disease-free survival (DFS) at 5 years were 43.5% and 41.8%, respectively. The 5-year OS was 53.5% (95% CI 34.5%-72.5%) and 5-year DFS was 52% (95% CI 33%-71%) in patients who underwent allo-SCT in CR1, compared with 31.9% (95% CI, 9%-54.8%) and 29.4% (95% CI 7.6%-51.2%) in those who underwent allo-SCT in ≥CR2. On multivariate analysis, disease status at SCT remained significantly associated with OS (P = .007), DFS (P = .002), and CIR (P = .000). The presence of extramedullary disease at diagnosis had no effect on the different outcomes. Grade II-IV acute GVHD was significantly associated with a lower OS (P = .006) and DFS (P = .01). Our data indicate that allo-SCT represents an effective treatment for HR T-ALL, particularly when performed in CR1.

Vascular function and handgrip strength in rheumatoid arthritis patients.

OBJECTIVE: To examine the relationship of handgrip strength with forearm blood flow (BF) and vascular resistance (VR) in rheumatoid arthritis (RA) patients. METHODS: Forearm BF at rest (RBF) and after upper arm occlusion (RHBF), and handgrip strength were examined in 78 individuals (RA = 42 and controls (CT) = 36). Subsequently, VR at rest (RVR) and after occlusion (RHVR) were calculated. RESULTS: The patients' RBF (P = 0.02) and RHBF (P = 0.0001) were less, whereas RVR (P = 0.002) and RHVR (P = 0.0001) were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P = 0.0001). Finally, handgrip strength was directly associated with RBF (r = 0.43; P = 0.0001), and RHBF (r = 0.5; P = 0.0001), and inversely related to RVR (r = -0.3; P = 0.009) and RHVR (r = -0.3; P = 0.007). CONCLUSION: The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals.

A population-based study of the epidemiology and clinical features of adults with acute myeloid leukemia in Algeria: report on behalf of the Algerian Acute Leukemia Study Group.

BACKGROUND AND OBJECTIVES: In Algeria, the incidence of hematologic malignancies has been difficult to estimate for many years. Today, many hematological centers, including 14 university hospitals, have been developed in the entire north and have useful epidemiological data pertinent to acute myeloid leukemia (AML). We studied the incidence of AML and its subtypes, age distribution, geographic distribution and trends in the rate of diagnosis over the last 5 years in Algeria. Secondary goals were to study trends of referral of AML cases from various regions to specific centers to assess the needs for health infrastructure and change of current practices. DESIGN AND SETTING: Retrospective analysis of nationwide survey of all adult cases of AML (>16 years) diagnosed between 1 January 2006 and 31 December 2010. PATIENTS AND METHODS: A survey form was distributed to all departments of hematology at the 15 participating centers. RESULTS: The 1426 cases of AML diagnosed during the study period represented an annual incidence of 0.91/100000 persons with a male to female (M/F) ratio of 1:16 and a median age of 45 years (range, 16-82 years). Nationally, 20% of cases AML were diagnosed in the whole western region of the country, 47% in the central and 33% in the east. There was a trend of continuous increase in the rate with age and in the rate of diagnosis over the last 5 years. The most common subtype was M2, followed by M4 and M5. CONCLUSION: An overall increase in the number of AML patients diagnosed nationwide over the last five years indicates a need for additional health care resources including curative and therapy-intense strategies, such as stem cell transplant facilities to optimize outcome. The relatively younger age of patients compared to the Western countries may be due to the demographic composition of our population.

Successful treatment of steroid-refractory autoimmune thrombocytopenia associated with Castleman disease with anti-CD-20 antibody (rituximab).

Multicentric Castleman disease (MCD) is a lymphoproliferative disorder of incompletely understood etiology and with various clinical presentations. The best therapeutic option for this disease is not well established. MCD is known to be associated with autoimmune phenomena. A 70-year-old female patient of MCD with progressive nodal disease associated with autoimmune thrombocytopenia failed steroid treatment and showed a transient response to intravenous immunoglobulin. The patient achieved complete recovery of her platelet count and a very good response in nodal disease after 3 weekly doses of anti-CD-20 antibody (rituximab). Anti-CD20 antibody treatment could be a good therapeutic option for MCD, mainly when associated with immune-related disorders.

[Prevalence of extra-hepatic manifestations in infection with hepatitis C virus: study of 140 cases]. / Prévalence des manifestations extra hépatiques au cours des infections par le virus de l'hépatite C : etude de 140 cas

AIM: To determine the extrahepatic manifestations (EHM) in chronic hepatitis C and to correlate signs with age, sex, degree of fibrosis and genotype of hepatitis C virus. METHODS: One hundred forty cases of chronic infection by hepatitis C virus were investigated in a period of 10 years. By interrogation, clinical examination and laboratory tests, the EHM were determined. Correlations with age, sex, viral genotype and degree of fibrosis were determined by the chi2 test. RESULTS: Mean age of our patients was 59 years (16-85 years). 74% were women. The genotype 1b was found in 75% of cases. The clinical EHM were found in 62% of cases: buccal dryness in 17.1% of cases, arthralgias in 33% of cases and fatigue in 65% of cases. 25% of patients had at least one biological EHM associated with chronic hepatitis C: proteinuria in 3 cases, cryoglobulinemia in 4 cases, dysthyroidism in 8 cases and more frequently a positive immunologie test. During the follow-up, we found one case of breast cancer, one case of rectal cancer, 2 cases of MALT lymphoma and one case pf splenic lymphoma. A positive correlation was found between the prevalence of EHM in chronic hepatitis C and the female sex. A degree of fibrosis ³ 2 in METAVIR classification was significantly associated with more important frequency of EHM. CONCLUSION: EHM should be screened systematically in chronic infection with HCV. Pathogenic mechanisms in a B lymph node proliferation or diabetes and outcome of these abnormalities under antiviral therapy should be further investigated.