Efthymia Vlachaki

Accuracy of Magnetic Resonance Imaging in Diagnosis of Liver Iron Overload: A Systematic Review and Meta-analysis

BACKGROUND & AIMS Guidelines advocate use of magnetic resonance imaging (MRI) to estimate concentrations of iron in liver, to identify patients with iron overload, and to guide titration of chelation therapy. However, this recommendation was not based on a systematic synthesis and analysis of the evidence for MRIs diagnostic accuracy. METHODS We conducted a systematic review and meta-analysis to investigate the diagnostic accuracy of MRI in identifying liver iron overload in patients with hereditary hemochromatosis, hemoglobinopathy, or myelodysplastic syndrome; liver biopsy analysis was used as the reference standard. We searched MEDLINE and EMBASE databases, the Cochrane Library, and gray literature, and computed summary receiver operating curves by fitting hierarchical models. We assessed methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS Our final analysis included 20 studies (819 patients, total). Sensitivity and specificity values varied greatly, ranging from 0.00 to 1.00 and from 0.50 to 1.00, respectively. Because of substantial heterogeneity and variable positivity thresholds, we calculated only summary receiver operating curves (and summary estimate points for studies that used the same MRI sequences). T2 spin echo and T2* gradient-recalled echo MRI sequences accurately identified patients without liver iron overload (liver iron concentration > 7 mg Fe/g dry liver weight) (negative likelihood ratios, 0.10 and 0.05 respectively). However, these MRI sequences are less accurate in establishing a definite diagnosis of liver iron overload (positive likelihood ratio, 8.85 and 4.86, respectively). CONCLUSIONS Based on a meta-analysis, measurements of liver iron concentration by MRI may be accurate enough to rule out iron overload, but not to definitely identify patients with this condition. Most studies did not use explicit and prespecified MRI thresholds for iron overload, therefore some patients may have been diagnosed inaccurately with this condition. More studies are needed of standardized MRI protocols and to determine the effects of MRI surveillance on the development of chronic liver disease and patient survival.

Pure Red Cell Aplasia and Lymphoproliferative Disorders: An Infrequent Association

Pure red cell aplasia (PRCA) is a rare bone marrow failure syndrome defined by a progressive normocytic anaemia and reticulocytopenia without leukocytopenia and thrombocytopenia. Secondary PRCA can be associated with various haematological disorders, such as chronic lymphocytic leukaemia (CLL) or non-Hodgkin lymphoma (NHL). The aim of the present review is to investigate the infrequent association between PRCA and lymphoproliferative disorders. PRCA might precede the appearance of lymphoma, may present simultaneously with the lymphoid neoplastic disease, or might appear following the lymphomatic disorder. Possible pathophysiological molecular mechanisms to explain the rare association between PRCA and lymphoproliferative disorders are reported. Most cases of PRCA are presumed to be autoimmune mediated by antibodies against either erythroblasts or erythropoietin, by T-cells secreting factors selectively inhibiting erythroid colonies in the bone marrow or by NK cells directly lysing erythroblasts. Finally, focus is given to the therapeutical approach, as several treatment regimens have failed for PRCA. Immunosuppressive therapy and/or chemotherapy are effective for improving anaemia in the majority of patients with lymphoma-associated PRCA. Further investigation is required to define the pathophysiology of PRCA at a molecular level and to provide convincing evidence why it might appear as a rare complication of lymphoproliferative disorders.

High Prevalence of Helicobacter pylori Infection in Greek Patients with Myelodysplastic Syndromes

Background/Aims/Methods: To determine the frequency of Helicobacter pylori infection (Hp-I) in 73 patients with myelodysplastic syndromes (MDS) and 40 controls, serologic analyses of Hp and 13C-urease breath tests (INFAI) were performed. Gastric mucosal biopsy specimens were obtained to determine the presence of Hp-I using a rapid urease test, i.e. the Campylobacter-like organism (CLO) test, and cresyl violet staining. Peripheral blood (PB) flow cytometry for CD3, CD4, CD8, CD14, CD19 and CD34 was conducted in 35 patients and in controls. Results:Hp-I was detected by: (a) serology in 75.34% of patients (p = 0.000), (b) INFAI in 57.69% of patients, (c) CLO in 60.71% of patients and (d) histological confirmation in 80.36% of patients (p = 0.001). No correlation between Hp-I and CD3, CD4, CD8, CD14, CD19 expression, leukemic transformation or death was observed. However, in 20 cases, significant variation in the PB lymphocytic proportion possibly attributable to Hp-I was ascertained, in contrast to the expected MDS ratio. Conclusion: Although there is no evidence for a causal relationship between Hp-I and MDS, the increased prevalence of Hp-I among the MDS patients is an interesting finding that deserves further investigation as it may indicate a common factor causing susceptibilities to both MDS and Hp-I or that Hp might influence the pathophysiology of MDS.

Eosinophilic pneumonia associated with heroin inhalation: a case report

ZusammenfassungMedikamente sind eine bekannte Ursache für eine Lungeneosinophilie. Es gibt einige Fallberichte über Patienten mit akuter eosinophiler Pneumonie in Verbindung mit Kokainkonsum. Veränderte Gewohnheiten des Heroinkonsums, mit Verschiebung vom intravenösen Gebrauch zum Heroinrauchen/Inhalation, können zu häufigerem Auftreten einer Heroin-verursachten Lungeneosinophilie führen. Berichtet wird der Fall eines Patienten, der ungefähr 10 Jahre lang Heroin inhaliert hatte. Er präsentierte sich mit Fieber, Husten, Atemnot und pleuritischem Schmerz in der Brust. Die Röntgenuntersuchung des Thorax zeigte einen einseitigen Pleuraerguß mit segmentaler Atelektase. Die Analyse des Pleuraergusses und der bronchoalveolaren Lavage zeigte eine signifikante Eosinophilie, womit die Diagnose einer eosinophilen Pneumonie gegeben war. Durch Heroinabstinenz und Kortikosteroidbehandlung konnte eine schnelle Genesung erzielt werden.SummaryDrugs are known to be a cause of pulmonary eosinophilia and several case reports of acute eosinophilic pneumonia associated with the use of cocaine have been reported. The changing pattern of heroin use, with a shift from intravenous use to smoking/inhalation of the substance, may lead to increased prevalence of heroin-induced pulmonary eosinophilia. We report on a case of a patient who had been inhaling heroin for about ten years. He presented with fever, cough, dyspnea and pleuritic chest pain. Chest radiograph showed unilateral pleural effusion with segmental atelectasis. Examination of pleuritic fluid aspirate and bronchoalveolar lavage fluid revealed significant eosinophilia. He was diagnosed with acute eosinophilic pneumonia. Rapid remission was achieved after heroin abstinence and initiation of corticosteroid treatment.

Haematoma caused by bone marrow aspiration and trephine biopsy

We report a case of a bone marrow aspiration and trephine biopsy (BMATB) associated haematoma in an 85-years old male without any predisposing risk factors. Six days after BMATB, he suffered from a massive thigh and buttock haematoma and a fall in haematocrit. It is important to know that BMATB can have complications aiding early recognition and therapy.

Total remission of severe immune thrombocytopenia after short term treatment with romiplostim.

Immune thrombocytopenia (ITP) in adults is an acquired chronic immune-mediated disorder defined by isolated thrombocytopenia. In recent years, an improved understanding of the pathophysiology of ITP has been achieved and it is now accepted that the disorder is due to increased platelet destruction and decreased platelet production from megakary-ocytes. Thrombopoietin (TPO)-receptor agonists (romiplostim and eltrombopag) are new therapeutic modalities in the treatment of ITP. Here we describe a case of an elderly patient with severe ITP who presented complete remission after short-term use of romiplostim (only 3 weekly doses). This finding is quite interesting as the TPO-receptor agonists are, so far, believed to rarely lead to off-treatment sustained remission. The common notion of long-term use of romiplostim could be reexamined in future studies. Furthermore, the short term treatment with romiplostim may reduce the cost and the risk of side effects.

Insulin sensitivity assessment with euglycemic insulin clamp in adult β-thalassaemia major patients

Objective:  To assess insulin sensitivity in young adult normoglycemic β‐thalassaemia major patients.

Iron chelation therapy of transfusion-dependent β-thalassemia during pregnancy in the era of novel drugs: is deferasirox toxic?

The life expectancy of thalassemic patients has increased, and now approaches that of healthy individuals, thanks to improved treatment regimens. However, pregnancy in women with β-Thalassemia Μajor remains a challenging condition. Recent advances in managing this haemoglobinopathy offer the potential for safe pregnancies with favorable outcome. However, clinical data regarding the use of chelation therapy during pregnancy are limited, and it is unclear whether these agents impose any risk to the developing fetus. Successful pregnancies following unintentional treatment with deferoxamine or deferasirox have rarely been reported. Generally, chelators are not recommended during pregnancy. Regarding the new oral chelators, data on fetotoxicity are lacking. In the present study, we describe the evolution and successful outcome of nine pregnancies in six Greek thalassemic women who received deferasirox inadvertently during early pregnancy, and review the literature regarding fetal anomalies due to chelators. Use of chelation before embarking upon a non-programmed pregnancy remains a difficult and unresolved question. In our study, chelation treatment during pregnancy did not prevent the delivery of healthy children. Nonetheless, the use of deferasirox is contraindicated in pregnant women, based on the product label. Deferasirox should only be used during pregnancy if the potential benefit outweighs the potential fetal risk.

Potential impact of Helicobacter pylori-related metabolic syndrome on upper and lower gastrointestinal tract oncogenesis

Both Helicobacter pylori infection and metabolic syndrome present significant global public health burdens. Metabolic syndrome is closely related to insulin resistance, the major underlying mechanism responsible for metabolic abnormalities, and Helicobacter pylori infection has been proposed to be a contributing factor. There is growing evidence for a potential association between Helicobacter pylori infection and insulin resistance, metabolic syndrome and related morbidity, including abdominal obesity, type 2 diabetes mellitus, dyslipidemia, hypertension, all of which increase mortality related to cardio-cerebrovascular disease, neurodegenerative disorders, nonalcoholic fatty liver disease and malignancies. More specifically, insulin resistance, metabolic syndrome and hyperinsulinemia have been associated with upper and lower gastrointestinal tract oncogenesis. Apart from cardio-cerebrovascular, degenerative diseases and nonalcoholic fatty liver disease, a number of studies claim that Helicobacter pylori infection is implicated in metabolic syndrome-related Barretts esophagus and esophageal adenocarcinoma development, gastric and duodenal ulcers and gastric oncogenesis as well as lower gastrointestinal tract oncogenesis. This review summarizes evidence on the potential impact of Helicobacter pylori-related metabolic syndrome on gastroesophageal reflux disease-Barretts esophagus-esophageal adenocarcinoma, gastric atrophy-intestinal metaplasia-dysplasia-gastric cancer and colorectal adenoma-dysplasia-colorectal cancer sequences. Helicobacter pylori eradication might inhibit these oncogenic processes, and thus further studies are warranted.

Treatment of chronic hepatitis C with direct‐acting antivirals in patients with β‐thalassaemia major and advanced liver disease

Interferon‐based regimens for chronic hepatitis C (CHC) were often deferred in patients with β‐thalasaemia major (β‐TM) due to poor efficacy and tolerance. Current guidelines recommend direct‐acting antivirals (DAAs) for these patients. The aim of this study was to assess the safety and efficacy of DAAs in patients with β‐TM and advanced liver disease due to CHC. Patients were recruited from eight liver units in Greece. The stage of liver disease was assessed using transient elastography and/or liver histology. Five regimens were used: sofosbuvir (SOF) + ribavirin (RBV); SOF + simeprevir ± RBV; SOF + daclatasvir ± RBV; ledipasvir/SOF ± RBV and ombitasvir/paritaprevir‐ritonavir + dasabuvir ± RBV. Sixty‐one patients (median age 43 years) were included. The majority of patients was previously treated for hepatitis C (75%) and had cirrhosis (79%). Viral genotype distribution was: G1a: n = 10 (16%); G1b: n = 22 (36%); G2: n = 2 (3%); G3: n = 14 (23%); G4: n = 13 (22%). The predominant chelation therapy was a combination of deferoxamine and deferiprone (35%). Overall sustained virological response rates were 90%. All treatment regimens were well tolerated and no major adverse events or drug‐drug interactions were observed. Approximately half of the patients who received RBV (7/16, 44%) had increased needs for blood transfusion. Treatment of CHC with DAAs in patients with β‐TM and advanced liver disease was highly effective and safe.