Patient/family views on data sharing in rare diseases: study in the European LeukoTreat project

The purpose of this study was to explore patient and family views on the sharing of their medical data in the context of compiling a European leukodystrophies database. A survey questionnaire was delivered with help from referral centers and the European Leukodystrophies Association, and the questionnaires returned were both quantitatively and qualitatively analyzed. This study found that patients/families were strongly in favor of participating. Patients/families hold great hope and trust in the development of this type of research. They have a strong need for information and transparency on database governance, the conditions framing access to data, all research conducted, partnerships with the pharmaceutical industry, and they also need access to results. Our findings bring ethics-driven arguments for a process combining initial broad consent with ongoing information. On both, we propose key item-deliverables to database participants.     

EZH2, new diagnosis and prognosis marker in acute myeloid leukemia patients

PurposeAcute myeloid leukemia (AML) is a heterogeneous disease. The discovery of novel discriminative biomarkers remains of utmost value for improving outcome predictions. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase of H3K27me3. It is frequently up-regulated in human cancers and associated with silencing of differentiation genes. We aimed herein to investigate the prevalence and prognosis impact of somatic EZH2 mutations and their potential associations with other prognostic markers FLT3, NPM1, DNMT3A and IDH2.Materials and methodsOur study population was composed of 211 Tunisian patients with de novo AML and 14 healthy donors. The 11 last exons coding the set domain of EZH2 were investigated by PCR and Sanger sequencing.ResultsEZH2 mutations were identified in 66/211 (31%) patients with a sex ratio of 1.06. The presence of EZH2 mutations was statistically significantly associated with failure consolidation therapy (p = 0.004). There were no differences in the incidence of EZH2 mutations and FLT3-ITD, NPM1, DNMT3A and IDH2 mutations. When EZH2 mutations were associated with those of FLT3 or IDH2, a short duration of progression free survival was observed (p < 0.05). Moreover, CD7 aberrant markers conferred a poor prognosis in EZH2 mutated patients (p < 0.05).ConclusionsGiven these data we conclude that EZH2 mutations are frequent in our patients, and can be used as a prognosis marker in combination with FLT3, IDH2 mutations and CD7 marker, to stratify AML patients and to guide therapeutic decisions.     

Primary cutaneous plasmacytoma

Primary cutaneous plasmacytoma (PCP) is a rare cutaneous B cell lymphoma. We report a case of PCP in a 64 year old woman presenting with a nodular lesion of the left cheek. Histologically, the lesion was composed predominately of variably maturated plasma cells with monotypic expression of lambda chain. Extracutaneous localizations of the disease had been excluded. The prognosis of PCP is better than that of the metastatic cutaneous lesion of myeloma. The main prognosis factors are the size tumor and clinical presentation (solitary, versus multiple lesions). Solitary lesions of the PCP are treated by surgical excision and sometimes local radiotherapy.     

Malignant proliferating trichilemmal tumor

Proliferating trichilemmal tumor (PTT) is a rare distinctive lesion that usually occurs in the scalp of elderly women. About 40 cases of malignant PTTs have been reported. Alternatively, some authors have proposed that all PTT are squamous cell carcinomas. We report a case of a malignant PTT on the scalp in 44-year-old man. Clinical features and histological criteria for diagnosis of malignant versus benign PTT are discussed.     

Emergency feasibility in medical intensive care unit of extracorporeal life support for refractory cardiac arrest

Objective To report the feasibility, complications, and outcomes of emergency extracorporeal life support (ECLS) in refractory cardiac arrests in medical intensive care unit (ICU). Design and setting Prospective cohort study in the medical ICU in a university hospital in collaboration with the cardiosurgical team of a neighboring hospital. Patients Seventeen patients (poisonings: 12/17) admitted over a 2-year period for cardiac arrest unresponsive to cardiopulmonary resuscitation (CPR) and advanced cardiac life support, without return of spontaneous circulation. Interventions ECLS femoral implantation under continuous cardiac massage, using a centrifugal pump connected to a hollow-fiber membrane oxygenator. Measurements and results Stable ECLS was achieved in 14 of 17 patients. Early complications included massive transfusions (n = 8) and the need for surgical revision at the cannulation site for bleeding (n = 1). Four patients (24%) survived at medical ICU discharge. Deaths resulted from multiorgan failure (n = 8), thoracic bleeding (n = 2), severe sepsis (n = 2), and brain death (n = 1). Massive hemorrhagic pulmonary edema during CPR (n = 5) and major capillary leak syndrome (n = 6) were observed. Three cardiotoxic-poisoned patients (18%, CPR duration: 30, 100, and 180 min) were alive at 1-year follow-up without sequelae. Two of these patients survived despite elevated plasma lactate concentrations before cannulation (39.0 and 20.0 mmol/l). ECLS was associated with a significantly lower ICU mortality rate than that expected from the Simplified Acute Physiology Score II (91.9%) and lower than the maximum Sequential Organ Failure Assessment score (> 90%). Conclusions Emergency ECLS is feasible in medical ICU and should be considered as a resuscitative tool for selected patients suffering from refractory cardiac arrest. This article is discussed in the editorial available at:     

T Cell-Replete Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for Hodgkin Lymphoma Relapsed after Autologous Transplantation: Reduced Incidence of Relapse and of Chronic Graft-versus-Host Disease Compared with HLA-Identical Related Donors

Allogeneic hematopoietic stem cell transplantation (SCT) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) relapsing after autologous SCT (ASCT), but the incidence of disease relapse is still high. We performed a retrospective study on 64 patients with HL relapsing after ASCT to compare outcomes after HLA-identical SCT (HLAid-SCT; n?=?34) and haploidentical SCT with post-transplantation cyclophosphamide (PT-Cy) (Haplo-SCT; n?=?30). All patients engrafted, with a significantly shorter median time for neutrophil and platelet engraftment after HLAid compared with Haplo-SCT (14 days versus 19 days and 11 days versus 23 days, respectively; P?<?.005). With a median follow-up of 47 months, 3-year overall survival (OS), 3 -year progression-free survival (PFS), and 1-year nonrelapse mortality (NRM) were 53%, 44% and 17%, respectively. Recipients of Haplo-SCT were less likely to experience disease relapse (3-year cumulative incidence of relapse, 13% versus 62%; P?=?.0001) and chronic graft- versus-host disease (GVHD; 3% versus 32%; P?=?.003), resulting in improved PFS (60% versus 29%; P?=?.04) and GVHD-free/relapse-free survival (47% versus 17%; P?=?.06). The 3-year OS did not differ between the 2 groups (56% versus 54%; P?not significant), and NRM was higher after Haplo-SCT, but the difference did not reach statistical significance (26% versus 9%; P?=?.09). On multivariate Cox regression analysis, receipt of Haplo-SCT (hazard ratio [HR], .17; P?=?.02) and achieving optimal disease control (complete remission before SCT: HR, .6; P?<?.0001) were the only independent variables associated with a reduced risk of disease relapse. Haplo-SCT is a valid option for patients with HL relapsing after ASCT, with a reduced incidence of relapse compared with HLAid SCT.     

Long-term liver disease in methylmalonic and propionic acidemias

Background and objectives

Patients affected with methylmalonic acidemia (MMA) and propionic acidemia (PA) exhibit diverse long-term complications and poor outcome. Liver disease is not a reported complication. The aim of this study was to characterize and extensively evaluate long-term liver involvement in MMA and PA patients.

The expression of MDM2 in gastrointestinal stromal tumors: immunohistochemical analysis of 35 cases

Background

Gastrointestinal stromal tumors (GIST) are the most common primary mesenchymal tumors of the digestive system. The assessment of their biological behavior still remains a scientific challenge. To date, there are no well-established biological prognostic markers of GIST. Our aim is to study the expression of the MDM2 oncoprotein in GIST through an immunohistochemical analysis.

Methods

It was a retrospective study of 35 cases of GIST diagnosed from 2009 to 2012 in the department of pathology of Hassan II university hospital, Fès, Morocco. MDM2 immunohistochemical staining was performed on archival paraffin-embedded and formalin-fixed specimens (with a threshold of nuclear positivity >?10%). Analysis of correlations between MDM2 immunoexpression and clinicopathological features of GIST has been performed.

Results

The mean age was 55.23 years (range 25–84 years) with a male predominance (sex ratio?=?1.5). The stomach was the main site of GIST, with 17 cases (48.57%) followed by the small bowel (9 cases, 25.71%). The spindle cell type GIST was the most frequent morphological variant (29 cases, 82.85%). Tumor necrosis was present in 8 cases (22.85%). Two patients (5.71%) had very low risk GIST, 5 (14.28%) had low risk GIST, 7 patients (20%) had intermediate risk tumors. The remaining 21 cases (60%) had high risk GIST. At the time of diagnosis, 9 patients (25.71%) had metastatic tumors. At immunohistochemical analysis, 40% of cases (14 patients) stained positive for MDM2. Of these MDMD2-positive tumors, 11/14 (78.57%) had high risk tumors and 8/14 cases (57.14%) presented with metastatic GIST. MDM2 positivity was significantly associated with the metastatic status (p?=?0.001).

Conclusion

The current study suggests that MDM2 immunohistochemical expression is a negative histoprognostic factor in GIST with a statistically significant correlation with metastasis.

     

Distinct Zika Virus Lineage in Salvador,Bahia, Brazil

Sequencing of isolates from patients in Bahia, Brazil, where most Zika virus cases in Brazil have been reported, resulted in 11 whole and partial Zika virus genomes. Phylogenetic analyses revealed a well-supported Bahia-specific Zika virus lineage, which indicates sustained Zika virus circulation in Salvador, Bahia’s capital city, since mid-2014.Key words: Zika virus, ZIKV, flaviviruses, Bahia, Brazil, mosquito-borne infections, outbreak surveillance, metagenomic next-generation sequencing, viral genome assembly, capture probe enrichment, phylogenetic analysis, molecular clock, viruses, vector-borne infectionsZika virus is an arthropodborne RNA virus primarily transmitted by mosquitoes of the species Aedes (1). The virus has 2 genotypes: African, found only in the continent of Africa; and Asian, associated with outbreaks in Southeast Asia, several Pacific islands, and, recently, the Americas (2). In May 2015, Brazil reported its first autochthonous cases of Zika virus infection, which occurred in northeast Brazil (3,4). As of June 30, 2016, all 27 federal states in Brazil had confirmed Zika virus transmission (http://www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=270&gid=35262&lang=en).The rapid geographic expansion of Zika virus transmission and the virus’s association with microcephaly and congenital abnormalities (5) demand a rapid increase in molecular surveillance in areas that are most affected. Molecular surveillance is particularly relevant for regions where other mosquitoborne viruses, particularly dengue and chikungunya viruses, co-circulate with Zika virus (2); surveillance on the basis of clinical symptoms alone is highly inaccurate. Genetic characterization of circulating Zika virus strains can help determine the origin and potential spread of infection in travelers returning from Zika virus–endemic countries. Previous analyses have suggested that Zika virus was introduced in the Americas at least 1 year before the virus’s initial detection in Brazil (1). The state of Bahia, Brazil, reported most (93%) suspected Zika virus infections in Brazil during 2015 (2), including cases of Zika virus–associated fetal microcephaly (6); however, except for 1 complete genome, no genetic information from the region has been available (2,7). We report molecular epidemiologic findings resulting from 11 new complete and partial Zika virus genomes recovered from serum samples from patients at the Hospital Aliança in the city of Salvador in Bahia, Brazil.