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Hemic and Lymphatic Diseases - Top 30 Publications

Amelioration of Dalton's lymphoma-induced angiogenesis by melatonin.

For tumor to grow beyond 1-2 mm(3) size, tumor recruits new blood vessels referred as angiogenesis; therefore, targeting angiogenesis can be a promising strategy to suppress cancer progression. In this study, in order to develop a good angiogenesis model, we investigated effect of Dalton's lymphoma on angiogenesis and further monitored the role of melatonin on regulation of angiogenesis. To evaluate angiogenesis, endothelial cells were isolated from main thoracic aorta and cultured in vitro in the presence or absence of Dalton's lymphoma supplemented with or without melatonin to monitor their role on its proliferation and migration, a hallmark of angiogenesis. Chick chorioallantoic membrane as well as mice mesentery which allows in vivo studies of tumor angiogenesis and testing of anti-angiogenic molecules was used to validate the in vitro analysis. To further extend our understanding about the regulation of the angiogenesis, we evaluated expression of tissue inhibitor of metalloproteinases 3, vascular endothelial growth factor, vascular endothelial growth factor receptor, and fibroblast growth factor in Dalton's lymphoma cells and mesentery by semiquantitative and quantitative reverse transcription polymerase chain reaction analysis. Dalton's lymphoma ascites induced significant increase in endothelial cell proliferation, migration, and sprouting of the tertiary branching in chorioallantoic membrane and mesentery of Dalton's lymphoma-bearing mice, whereas melatonin treatment led to their inhibition in a dose-dependent manner. Semiquantitative and quantitative reverse transcription polymerase chain reaction analysis of melatonin-treated Dalton's lymphoma cells and mesentery tissue clearly demonstrated restoration of angiogenesis-related genes tissue inhibitor of metalloproteinases 3 and reduction of vascular endothelial growth factor, vascular endothelial growth factor receptor, and fibroblast growth factor messenger RNA expression. Taken together, our results strongly demonstrate that Dalton's lymphoma provides pro-angiogenic environment leading to significant increase in angiogenesis, and further melatonin treatment reduced the Dalton's lymphoma ascites-induced angiogenesis implying that Dalton's lymphoma can serve as a very good model to study angiogenesis as well as for screening of drugs that can target angiogenesis.

Intimate cross-talk between cancer cells and the tumor microenvironment of B-cell lymphomas: The key role of exosomes.

B-cell lymphomas are composed of tumor cells and the tumor microenvironment, which is conventionally thought to be composed of a mixture of stromal cells, blood vessels, immune cells, and non-cell components, such as extracellular matrix, cytokines, and chemokines. Exosomes, small endocytically derived vesicles that have been proved to be present in a variety of tumor niches and involved in mediating cell signaling networks, are increasingly regarded as important components of tumor microenvironment. In this review, we first focus on the biogenesis, biodistribution, transportation, and other general characteristics of exosomes and then highlight the vital roles of exosomes in lymphomagenesis and disease progression, particularly from the perspective of immune dysfunction, virus infection, and therapeutic resistance mechanisms.

Incomplete Miller-Fisher Syndrome with Advanced Stage Burkitt Lymphoma.

Lymphoma-associated incomplete Miller-Fisher syndrome is very rare.

Blinatumomab for Acute Lymphoblastic Leukemia.

Blinatumomab for Acute Lymphoblastic Leukemia.

Measurement of Hemoglobin A1c in Patients With Sickle Cell Trait-Reply.

Measurement of Hemoglobin A1c in Patients With Sickle Cell Trait.

Evolution of Purpura Fulminans.

Myeloproliferative Neoplasms.

Clinical features and prognostic factors of adult secondary hemophagocytic syndrome: Analysis of 47 cases.

This study aimed to investigate the relationship between clinical features and prognosis of adult secondary hemophagocytic syndrome (HPS).A retrospective analysis was conducted on the pathogenesis, clinical manifestations, laboratory examinations, treatment options, and prognosis of 47 patients with adult secondary HPS diagnosed from January 2013 to December 2015.The average age at disease onset was (46.26 ± 18.98) years with a male:female ratio of 1:1.14. Thirteen patients died, with the highest mortality rate in patients with HPS underlying blood system malignancy (33.33%, 2/6). The mortality rate in patients with HPS underlying autoimmune disorders was the lowest (18.75%, 3/16). The Kaplan-Meier analysis indicated that signs of hemorrhage, pulmonary and nervous system involvement, serous effusion, and decrease in the blood platelet count were associated with death. The Cox regression analysis revealed that signs of hemorrhage, pulmonary involvement, serous effusion, and nervous system involvement were independent risk factors of patient death.Adult secondary HPS has multiple etiologies and diversified clinical features. The risk of death increases in patients with signs of hemorrhage, serous effusion, pulmonary involvement, and nervous system involvement.

Gene Therapy in a Patient with Sickle Cell Disease.

Antimicrobial resistance patterns, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients with hematological disease: A monocenter retrospective study in China.

The aim of this retrospective analysis was to evaluate the antimicrobial resistance, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients in a single hematological center in China. A retrospective case-control study of 157 adult hematological patients with 168 episodes of E coli bacteremia was initiated from April 2012 to July 2015. Antimicrobial susceptibility as well as antimicrobial co-resistance rates were analyzed. Clinical features and outcomes were also studied. In addition, risk factors for septic shock and death were investigated. Among the 553 positive blood isolates during the study period, the prevalence of E coli was 33.3% and ESBL production strains represented 61.9% of those examined. In all the E coli strains isolated, 85.6% were multidrug-resistance (MDR), 2.4% were extensive drug resistance (XDR), and 6.0% were resistant to carbapenems. More MDR phenotype was noted in ESBL-EC strains (98.6% vs 62.8%, P<.001) and isolates from neutropenic patients (98.6% vs 62.8%, P < .001). In the antimicrobial susceptibility test, carbapenems and amikacin exhibited not only higher in vitro activity against E coli (94.0% and 92.0%, respectively), but lower co-resistance rates to other antibiotics. Carbapenem resistant strains retained full sensitivity to tigecycline and 60% to amikacin. Piperacillin/tazobatam was the third sensitive drug to both ESBL-EC (77.1%) and non-ESBL-EC (86.0%). In our series, 81.6% episodes received appropriate initial antibiotic treatment and no significant decrease in it was found in bacteremia due to ESBL E coli and patients with neutropenia, septic shock. Septic shock was noted in 15.5% patients and the overall 30-day mortality rate was 21.7%. Multivariate analysis revealed that induction chemotherapy (OR 2.126; 95% CI 1.624-11.332; P = .003) and polymicrobial infection (OR 3.628; 95% CI 1.065-21.219; P = .041) were risk factors for septic shock, whereas male (OR 2.223; 95% CI 1.132-12.022; P < .01) and septic shock (OR 52.359; 95% CI 19.951-292.690; P = .030) were risk factors for death.In the hematology department, ESBL-producing and MDR are widely prevalent in E coli bacteremia which is still a major life-threatening problem, especially for patients with septic shock. For empirical antimicrobial therapy, combination based on aminoglycoside, especially amikacin, will be helpful to increase the antimicrobial coverage against ESBL-EC while combining tigecycline with aminoglycoside should be considered for seriously carbapenem-resistant infectious patients.

Gene Therapy in a Patient with Sickle Cell Disease.

Cutaneous leukocytoclastic vasculitis: about 85 cases.

Clinical manifestation, etiology and outcome of leukocytoclastic vasculitis are little studied. The aim of our study was to examine epidemiological, clinical etiological, and evolutionary characteristics of this entity. We conducted a cross-sectional data collection from medical records of 85 patients with leukocytoclastic vasculitis in the Department of Dermatology at the Farhat Hached University Hospital, Sousse between January 2000 and December 2013. Epidemiological, clinical, paraclinical, etiological data sheets had been completed for each patient. The average age of patients was 47.65 years, ranging between 10 and 78 years. Fifty-three women and 32 men were registered (sex ratio = 0.6). Cutaneous manifestations were dominated by vascular purpura (88.2%). The most common causes of leukocytoclastic vasculitis were systemic diseases (51%), infection (20%) and neutrophilic dermatoses (14.5%). Other causes were drugs (9.1%) and hematologic malignancies (5.4%). The cause of leukocytoclastic vasculitis was not detected in 30 patients (35, 3%). Two predictive factors associated with the acute outcome were retained: the presence of a recent infection (p= 0.014) and drug intake before the rash (p= 0.013). Chronic evolution was positively correlated with antinuclear antibodies (p= 0.009) and cryoglobulinemia (p=0.025). Our study highlights the multitude of causes of leukocytoclastic vasculitis. The search for an underlying disease is an imperative in order to ensure better therapeutic management.

A rare cause of exophthalmia: intraorbital cavernous hemangioma (about a case).

Cavernous hemangioma is the most frequent primary benign vascular tumor of the orbit in the adult; the median age of diagnosis is 42 years with a female predominance. This tumor develops slowly and has no tendency for spontaneous regression; it is electively located at the level of the retro-ocular muscular cone but it can develop in the extraconic space. Clinically it appears as progressive irreducible, non-pulsating, painless (unless there's an unexpected complication) exophthalmia, associated with decrease in visual acuity in 2/3 of cases. The diagnosis is easily confirmed by imaging, which allows to precisely locate the tumor in relation to the optic nerve and the oculomotor muscles and to indicate the type of surgical approach. Surgical resection should be complete; it is usually simple because the tumor is limited and perfectly cleavable. Surgical approach is established on the basis of tumor volume and above all of the seat of the lesion. Functional prognosis is good and recurrences are rare. We here report the case of a 44-year old patient with orbital cavernous hemangioma revealed by exophthalmia.

Splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a rare B-cell lymphoma, well defined according to the 2016 WHO classification of tumors of the hematopoietic tissue, which can raise diagnostic problems. We report the case of a 72-year old patient, hospitalised for exploration of a massive splenomegaly confirmed by computed tomography (CT). Laboratory tests were normal. The patient underwent splenectomy. Microscopic examination of the surgical specimen showed widespread lymphomatous proliferation in small cells associated with CD20 marker. CD 5 and CD 43 were negative. The diagnosis of SMZL was retained. SMZL accounts for less than 2% of non-Hodgkin lymphomas. It affects subjects older than 50 years, and it is usually characterized by the presence of a massive splenomegaly without lymphadenopathies. Blood count shows inconsistent presence of villous lymphocytes in three quarters of cases. The diagnosis is essentially based on anatomopathological evaluation and shows constant nodular involvement or sometimes diffuse involvement of white pulp of the splenic parenchyma.Tumor cells are small in size with B lymphoid markers expression: CD19, CD20, CD22, CD79. They are negative for CD5, CD10, cyclin D1 and CD43. No specific cytogenetic abnormality in SMZL has been identified. SMZL is an indolent lymphoma whose treatment is not codified, depending on prognostic factors. Mortality is related to the risk of its transformation to large cell lymphoma.

Recombinant esterase from Corynebacterium pseudotuberculosis in DNA and subunit recombinant vaccines partially protects mice against challenge.

We tested the efficacy of the esterase encoded by cp1002_RS09720 from Corynebacteriumpseudotuberculosis in recombinant subunit and DNA caseous lymphadenitis (CLA) vaccines. This target was predicted as one of the best CLA vaccine candidates by mature epitope density analysis.

Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis.

Eosinophilic granulomatosis with polyangiitis is an eosinophilic vasculitis. Mepolizumab, an anti-interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis.

How is patient care for multiple myeloma advancing?

Treatment of multiple myeloma has undergone profound changes in the past years thanks to the increased understanding of the biology of the disease and the new treatment options. New drugs and effective approaches are currently available for the treatment of multiple myeloma, including immunomodulatory agents, proteasome inhibitors and autologous stem cell transplantation. Areas covered: We have described the recent updated criteria to start treatment in multiple myeloma and summarized clinical data from major studies including most recent agents. Particularly, results with pomalidomide, carfilzomib, ixazomib, monoclonal antibodies such as elotuzumab, daratumumab, and checkpoint inhibitors have been reported. Both transplant and non-transplant settings have been covered. Expert commentary: Despite the successful improvement in overall survival and time to relapse, multiple myeloma still remains incurable. Therefore, there is still an unmet need for new treatment strategies with novel mechanisms of action, like monoclonal antibodies, novel immunomodulators, and novel proteasome inhibitors. Implementation of these novel drugs in rationally designed therapies with a good balance of efficacy and safety should be carefully considered in order to improve outcome.

Silicone Injection-Related Granulomatous Hypercalcemia.

Cosmetic filler injections are known to cause a number of acute and chronic effects, including local inflammation, nodule formation and granulomatous reaction. The timeline of these events is highly variable, occurring from hours to decades following injection. In few cases, systemic effects have been observed. We report a case of granulomatous disease secondary to illicit silicone injection causing recalcitrant hypercalcemia. Additionally, we review the pathophysiology of inflammation in cosmetic filler injections, the prevailing understanding of hypercalcemia in granulomatous disease and summarize the most effective treatment modalities for this rare condition.

The Enhanced International Prognostic Index for Diffuse Large B-cell Lymphoma.

To explore the prognostic value of the enhanced International Prognostic Index (NCCN-IPI) for Asian patients with diffuse large B-cell lymphoma (DLBCL) treated in the rituximab era.

Fanconi Anemia and Laron Syndrome.

Fanconi anemia (FA) is a condition characterized by genetic instability and short stature, which is due to growth hormone (GH) deficiency in most cases. However, no apparent relationships have been identified between FA complementation group genes and GH. In this study, we thereby considered an association between FA and Laron syndrome (LS) (insulin-like growth factor 1 [IGF-1] deficiency).

Circularly permuted TRAIL plus thalidomide and dexamethasone versus thalidomide and dexamethasone for relapsed/refractory multiple myeloma: a phase 2 study.

Circularly permuted TRAIL (CPT) has exhibited promising efficacy as a mono-therapy or in combination with thalidomide for patients with multiple myeloma (MM). In this phase 2 study, the safety and efficacy of CPT in combination with thalidomide and dexamethasone (CPT + TD) was evaluated in patients with pretreated relapsed/refractory MM (RRMM).

Macrophage activation syndrome complicating family lymphohistiocytosis.

Macrophage activation syndrome (MAS) is an anatomoclinic entity due to inappropriate macrophage activation. It is a rare pathology, characterized by clinical signs that are not very specific and by biological elements. Their association must evoke the diagnosis. It can be classified as primary or secondary, its prognosis is still unclear. We report the case of a 3-year and 4-month-old infant admitted to our department with primary MAS in order to remind clinicians the importance of suspecting primary cause in specific situations.

A primary intestinal lymphangiectasia hiding the diagnosis of pleural and pericardial tuberculosis: a clinical observation.

Primary intestinal lymphangiectasia (Waldmann's disease) is an exudative enteropathy characterized by lymph leakage into the small bowel lumen leading to hypoalbuminemia, hypogammaglobulinemia and lymphopenia (particularly T-cell). The diagnosis is based on viewing the duodenal lymphangiectasia. A 20 years old female patient, treated for a primary intestinal lymphangiectasia, has consulted for anasarca. Etiological work-up reveals pleural and pericardial tuberculosis. The clinical aggravation of an enteropathy, particularly in adulthood, requires a search for a secondary etiology. Tuberculosis should be sought systematically.

A non-EDTA-dependent pseudothrombocytopenia: about a case.

Pseudothrombocytopenia is a rare phenomenon in laboratory explained by in vitro agglutination of platelets. Microscopic examination of the peripheral blood smear is of key importance to confirm the diagnosis and to avoid any inappropriate or dangerous clinical and therapeutic decision. Its occurrence in a patient, under treatment with heparin, raises the problem of differential diagnosis of heparin-induced thrombocytopenia. The aim of this study was to eliminate any confusion between this purely artefactual phenomenon and heparin-induced thrombocytopenia.

The safety of daratumumab for the treatment of multiple myeloma.

The overall survival of patients with multiple myeloma (MM) has changed dramatically in the last decade. MM remains an incurable plasma cell disorder but immunotherapy with monoclonal antibodies (MoAbs) has emerged as a promising treatment. Areas covered: Fully published, clinical trials including patients with relapsed or refractory MM were reviewed. Safety data of daratumumab (DARA) single-agent or in combination regimens have been addressed. Additionally, infusion-related reactions, data on special populations, and DARA-interference with laboratory testing, including assessment of MM response in patients have also been addressed. Expert opinion: Daratumumab both as single agent and in combination regimens has shown a favorable safety profile without significant increase in toxicities. Extensive clinical development of DARA is currently ongoing and given the efficacy that has been seen with this drug in clinical trials, DARA is likely to change the landscape of myeloma treatment.

Case 3-2017: A Man with Cardiac Sarcoidosis and New Diplopia and Weakness.

Case 14-2017 - A 20-Year-Old Man with Pain and Swelling of the Left Calf and a Purpuric Rash

Cytomegalovirus retinitis in a patient with secondary acute lymphosarcoma leukemia undergoing allogeneic hematopoietic stem-cell transplantation: A rare case report: a care-compliant article.

Cytomegalovirus (CMV) retinitis is a common opportunistic infection in immunocompromised patients, which may lead to blindness. CMV retinitis is not an uncommon infectious disease in patients with immune regulatory abnormalities, for example, human immunodeficiency virus (HIV) patients. However, CMV retinitis in a patient with acute lymphosarcoma leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) phase is very rare.