Diagnostic and Therapeutic Advances in Blastic Plasmacytoid Dendritic Cell Neoplasm: A Focus on Hematopoietic Cell Transplantation

AbstractBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is an exceedingly rare disorder categorized under acute myeloid leukemia by the World Health Organization. Phenotypically, malignant cells coexpress CD4+ and CD56+ without coexpressing common lymphoid or myeloid lineage markers. BPDCN frequently expresses CD123, TCL1, BDCA-2, and CD2AP. Restriction of CD2AP expression to plasmacytoid dendritic cells makes it a useful tool to help confirm diagnosis. Clonal complex chromosome aberrations are described in two-thirds of cases. Eighty percent of BPDCN cases present with nonspecific dermatological manifestations, prompting inclusion in the differential diagnosis of atypical skin rashes refractory to standard treatment. Prognosis is poor, with a median survival of less than 18 months. No prospective randomized data exist to define the most optimal frontline chemotherapy. Current practice considers acute myeloid leukemia-like or acute lymphoblastic leukemia–like regimens acceptable for induction treatment. Unfortunately, responses are short-lived, with second remissions difficult to achieve, underscoring the need to consider hematopoietic cell transplantation early in the disease course. Allografting, especially if offered in first remission, can result in long-term remissions. Preclinical data suggest a potential role for immunomodulatory agents in BPCDN. However, further research efforts are needed to better understand BPDCN biology and to establish evidence-based treatment algorithms that might ultimately improve overall prognosis of this disease

Potential role of killer immunoglobulin receptor genes among individuals vaccinated against hepatitis B virus in Lebanon

AIM: To explore the role of killer immunoglobulin receptor (KIR) genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus. METHODS: We recruited 101 voluntary participants between March 2010 and December 2011. Sera samples from vaccinated and non-vaccinated participants were tested for the presence of anti-HBs antibodies as a measure of protection against hepatitis B, hepatitis B surface antigen and hepatitis B core antibody as indicators of infection by enzyme-linked immunosorbent assay. KIR gene frequencies were determined by polymerase chain reaction. RESULTS: Sera samples from 99 participants were tested for the levels of anti-HBs as an indicator of protection (≥ 10 mIU/mL) following vaccination as defined by the World Health Organization international reference standard. Among the vaccinated participants, 47% (35/74) had anti-HBs titers above 100 mIU/mL, 22% (16/74) had anti-HBs ranging between 10-100 mIU/mL, and 20% (15/74) had values of less than 10 mIU/mL. We report the lack of significant association between the number of vaccine dosages and the titer of antibodies among our vaccinated participants. The inhibitory KIR2DL1, KIR2DL4, KIR3DL1, KIR3DL2, and KIR3DL were detected in more than 95%, whereas KIR2DL2, KIR2DL3, KIR2DL5 (KR2DL5A and KIR2DL5B) were expressed in 56%, 84% and 42% (25% and 29%) of participants, respectively. The observed frequency of the activating KIR genes ranged between 35% and 55% except for KIR2DS4, detected in 95% of the study participants (40.6% 2DS4*001/002; 82.2% 2DS4*003/007). KIR2DP1 pseudogene was detected in 99% of our participants, whereas KIR3DP*001/02/04 and KIR3DP1*003 had frequencies of 17% and 100%, respectively. No association between the frequency of KIR genes and anti-HBs antibodies was detected. When we compared the frequency of KIR genes between vaccinated individuals with protective antibodies titers and those who lost their protective antibody levels, we did not detect a significant difference. KIR2DL5B was significantly different among different groups of vaccinated participants (group I > 100 mIU/mL, group II 10-100 mIU/mL, group III < 10 mIU/mL and group IV with undetectable levels of protective antibodies). CONCLUSION: To our knowledge, this is the first study screening for the possible role of KIR genes among individuals vaccinated against hepatitis B virus (HBV). Our results can be used to design larger studies to better understand the role of KIR genes in protection against or susceptibility to HBV post vaccination

Molecular characterization, toxin detection and resistance testing of human clinical Clostridium difficile isolates from Lebanon

Clostridium (Clostridioides) difficile is the main cause for nosocomial diarrhoea in industrialised nations. Epidemiologic data on the pathogen’s occurrence in other world regions are still scarce. In this context we characterized with phenotypic and molecular genetic methods C. difficile isolates stemming from hospitalised patients with diarrhoea in Lebanon. From 129 stool samples of symptomatic patients at a tertiary care University hospital in Lebanon, a total of 107 C. difficile strains were cultivated and underwent ribotyping, toxin gene detection and antibiotic resistance testing. Ribotype 014 (RT014, 16.8%) predominated, followed by RT002 (9.3%), RT106 (8.4%) and RT070 (6.5%). Binary toxin gene-positive isolates (RT023, RT078 and RT126) were rarely detected and RT027 was absent. Interestingly, within one isolate only the toxin A gene (tcdA) was detected. Multiple-locus variable-number tandem repeat analysis (MLVA) revealed strong strain diversity in most RTs. The isolates were sensitive to metronidazole and vancomycin, and only a small proportion of strains displayed resistance against moxifloxacin, rifampicin, and clarithromycin (5.6%, 1.9%, and 2.8%), respectively. The data indicate that the genetic strain composition of Lebanese strains differs markedly from the situation seen in Europe and North America. Especially the epidemic RTs seen in the latter regions were almost absent in Lebanon. Interestingly, most strains showed almost no resistance to commonly used antibiotics that are suspected to play a major role in the development of C. difficile infection, despite frequent use of these antibiotics in Lebanon. Thus, the role of antimicrobial resistance as a major driving force for infection development remains uncertain in this area

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Élaboration de nanoparticules par ablation laser de cibles métalliques en milieu liquide et applications en catalyse

Nous avons élaboré des nanoparticules par ablation laser en milieux liquides, avec un laser YAG ( = 532 nm, pulse : 10Hz, 8ns, 40mJ) focalisé sur des cibles métalliques (Ni, Pd, Au) et bimétalliques (Au75Ag25, Ni75Pd25). Les caractéristiques physico-chimiques des nanoparticules formées ont été étudiées par ICP, TEM, EDX, UV-vis, XPS et PIXE. Dans le cas d'une cible de Ni dans l'eau des nanoparticules NiO, dont la taille diminue avec le temps d'ablation laser, ont été obtenues. L'effet du solvant sur les caractéristiques des nanoparticules a été étudié pour le Pd (eau et toluène) et l'Au (eau et MCH). Dans le cas du Pd, les particules obtenues dans l'eau présentent la structure cfc attendue ; celles obtenues dans le toluène ont une structure différente et sont souvent enrobées de carbone. Ceci est parfois le cas pour les plus grosses particules d'Au synthétisées dans le MCH. Les colloïdes de Pd déposés sur a-Al2O3 ont été testés dans l'oxydation totale du méthane. Les colloïdes d'or dans le MCH, testés dans l'époxydation du trans-stilbène, ont montré une bonne activité et une très bonne sélectivité en époxyde des plus petites particules d'or non supportées. Dans le cas des bimétalliques, nous avons obtenu des nanoparticules Au-Ag de composition identique à celle de la cible ; pour Ni-Pd, les particules obtenues sont homogènes en composition, mais celle-ci varie en fonction du temps d'ablation, et tend vers la composition nominale de la cible pour les plus forts temps. En conclusion, l'ablation laser en milieu liquide s'avère prometteuse pour obtenir des nanoparticules en solution, qui peuvent trouver des applications en catalyse, en particulier en milieu liquideWe synthesized colloidal nanoparticles by laser ablation in liquids using a YAG laser ( = 532 nm, pulse : 10Hz, 8ns, 40mJ) focused on metallic (Ni, Pd, Au) and bimetallic (Au75Ag25, Ni75Pd25) targets. The physico-chemical characteristics of the nanoparticles formed in solution were studied by ICP, TEM, EDX, UV-vis, XPS and PIXE. For Ni target in water, NiO nanoparticles were obtained. Their mean size decreases when laser ablation time increases. The effect of the solvent on the nanoparticles characteristics was studied for a Pd target (water and toluene) and on Au target (water and MCH). In the case of Pd, the particles obtained in water present fcc structure ; those obtained in toluene have a different structure and are often coated with carbon. This is also the case for some of the larger Au particles synthesized in MCH. Pd aqueous colloids were disposited on a-Al2O3, and were tested in the reaction of total oxidation of methane. Gold colloids in MCH were used as-prepared in the reaction of epoxidation of trans-stilbene, showing a good activity and a very food selectivity towards epoxide for the smallest unsupported gold particles. For bi-metallic samples Au75Ag25 and Ni75Pd25. We succeeded in preparing Au-Ag nanoparticles with homogeneous composition, similar to the one of the target. For Ni-Pd, the particles obtained are homogeneous in composition but it depends on the time of ablation, and approaches the nominal composition of the target for the higest time of ablation. In concoulsion, laser ablation in liquids is a promising method to obtain solutions of nanoprticles, which may find applications, particularly for catalysis in liquid mediaLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Pulmonary Embolism in a Sarcoidosis Patient Double Heterozygous for Methylenetetrahydrofolate Reductase Gene Polymorphisms and Factor V Leiden and Homozygous for the D-Allele of Angiotensin Converting Enzyme Gene

Sarcoidosis is a multisystem granulomatous disease of unknown etiology and pathogenesis. It presents in patients younger than 40 years of age. The lungs are the most commonly affected organ. Till the present day, there is no single specific test that will accurately diagnose sarcoidosis; as a result, the diagnosis of sarcoidosis relies on a combination of clinical, radiologic, and histologic findings. Patients with sarcoidosis have been found to have an increased risk of pulmonary embolism compared to the normal population. MTHFR and factor V Leiden mutations have been reported to increase the risk of thrombosis in patients. We hereby present a case of a middle aged man with sarcoidosis who developed a right main pulmonary embolism and was found to be double heterozygous for methylenetetrahydrofolate reductase gene polymorphisms and factor V Leiden and homozygous for the D-allele of the angiotensin converting enzyme gene

A Rare Case of Rectovaginal Fistula Due to Consensual Sexual Intercourse

Rectovaginal fistulae after sexual intercourse are rare. We report a healthy recently married 21-year-old woman who presented to the Jordan Healthcare Centre, Amman, Jordan in 2014 with a five-week history of passing flatus and stool from the vagina. Six weeks prior, she had sustained a rectovaginal injury during initial consensual sexual intercourse, leading to the development of a distal rectovaginal fistula. A successful transvaginal repair was performed nine weeks after presentation which resulted in the complete resolution of her symptoms

Primary synovial sarcoma of the kidney: a case report of complete pathological response at a Lebanese tertiary care center

Abstract Background Primary synovial sarcoma of the kidney is a rare type of soft tissue sarcoma. Its presenting features can resemble those of other renal tumors; rendering its early diagnosis, a dilemma. Several cases of renal synovial sarcoma have been reported in the literature with varying treatment options and outcomes. This article describes a rare case of primary renal synovial sarcoma and reviews all cases in the literature. Case presentation A 26-year-old male presented with flank pain and hematuria. Initially diagnosed with Wilm’s tumor, revision of pathology and histology, along with the immunohistochemical profile, confirmed, nevertheless, the diagnosis of primary monophasic synovial sarcoma of the kidney with the SYT-SSX2 fusion transcript. Follow-up, post nephrectomy, revealed recurrence within the lungs and at the surgical bed. Surgical resection followed by adjuvant chemotherapy regimen constituting of Doxorubicin and Ifosfamide, achieved complete pathological response. Conclusion In this case report, we emphasize the need for accurate diagnosis and prompt treatment. We propose multimodality treatment approach including surgery along with anthracycline-based chemotherapy to induce complete remission

Clinical Characteristics and Outcomes of Decompensated Cirrhosis Patients Admitted to Hospitals With Acute Pulmonary Embolisms: A Nationwide Analysis

INTRODUCTION: Cirrhosis is a significant cause of mortality and morbidity worldwide. Recent studies suggested that cirrhosis is associated with an increased risk of venous thromboembolism (VTE), which disproves the old belief that chronic liver disease coagulopathy is considered protective against VTE. We conducted a retrospective study which is to our knowledge the first of its kind to assess clinical characteristics and outcomes of decompensated cirrhosis (DC) patients admitted with acute pulmonary embolism (APE). METHODOLOGY: We used the National Inpatient Sample database for the years 2016-2019. All adults admitted to the hospitals with a primary diagnosis of APE were included. Patients less than 18 years old, missing race, gender, or age were excluded. Patients were divided into two groups, either having DC or not. A multivariate logistic regression model was built by using only variables associated with the outcome of interest on univariable regression analysis at P \u3c 0.05. RESULTS: 142 million discharges were included in the NIS database between the years 2016 and 2019, of which 1,294,039 met the study inclusion criteria, 6,200 patients (0.5%) had DC. For adult patients admitted to the hospitals with APE, odds of inpatient all-cause mortality were higher in the DC group than in patients without DC; OR of 1.996 (95% CI, 1.691-2.356, P-value \u3c 0.000). Also, vasopressor use, mechanical ventilation, and cardiac arrest were more likely to occur in the DC group, OR of 1.506 (95% CI, 1.254-1.809, P-value \u3c 0.000), OR of 1.479 (95% CI, 1.026-2.132, P-value 0.036), OR of 1.362 (95% CI, 1.050-1.767, P-value 0.020), respectively. In addition, DC patients tend to have higher total hospital charges and longer hospital length of stay, coefficient of 14521 (95% CI, 6752-22289, P-value \u3c 0.000), and a coefficient of 1.399 (95% CI, 0.848-1.950, P-value \u3c 0.000), respectively. CONCLUSION: This study demonstrates that DC is a powerful predictor of worse hospital outcomes in patients admitted with APE. An imbalance between clotting factors and natural anticoagulants produced by the liver is believed to be the primary etiology of thrombosis in patients with DC. The burden of APE can be much more catastrophic in cirrhotic than in non-cirrhotic patients; therefore, those patients require closer monitoring and more aggressive treatment