In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to SL-401, an interleukin-3 receptor targeted biologic agent.

Blastic plasmacytoid dendritic cell neoplasm is an aggressive malignancy derived from plasmacytoid dendritic cells. There is currently no accepted standard of care for treating this neoplasm, and therapeutic strategies have never been prospectively evaluated. Since blastic plasmacytoid dendritic cell neoplasm cells express high levels of interleukin-3 receptor α chain (IL3-Rα or CD123), antitumor effects of the interleukin-3 receptor-targeted drug SL-401 against blastic plasmacytoid dendritic cell neoplasm were evaluated in vitro and in vivo. The cytotoxicity of SL-401 was assessed in patient-derived blastic plasmacytoid dendritic cell neoplasm cell lines (CAL-1 and GEN2.2) and in primary blastic plasmacytoid dendritic cell neoplasm cells isolated from 12 patients using flow cytometry and an in vitro cytotoxicity assay. The cytotoxic effects of SL-401 were compared to those of several relevant cytotoxic agents. SL-401 exhibited a robust cytotoxicity against blastic plasmacytoid dendritic cell neoplasm cells in a dose-dependent manner. Additionally, the cytotoxic effects of SL-401 were observed at substantially lower concentrations than those achieved in clinical trials to date. Survival of mice inoculated with a blastic plasmacytoid dendritic cell neoplasm cell line and treated with a single cycle of SL-401 was significantly longer than that of untreated controls (median survival, 58 versus 17 days, P<0.001). These findings indicate that blastic plasmacytoid dendritic cell neoplasm cells are highly sensitive to SL-401, and support further evaluation of SL-401 in patients suffering from blastic plasmacytoid dendritic cell neoplasm.

Microbiological profile of multidrug resistant bacteria before and during COVID-19 in CHU Mohammed VI.

Background and Objectives: A new type of corona virus has caused Corona virus disease-19 and, subsequently, a global pandemic. All individuals are prone to the disease, so drastic measures were taken to prevent its spread. This study aimed to evaluate the impact of COVID-19 on the progression of the antimicrobial resistance rate by comparing two periods: before and during COVID-19. Materials and Methods: We used a cross-sectional design to investigate the Antimicrobial Resistance (AMR) rate before (03/2019 to 03/2020) and during COVID-19 (03/2020 to 03/2021) in a University Hospital in Marrakech. The data were analyzed using SPSS Version 25.0. Results: Among the 7106 specimens, there was a significant increase in the multidrug-resistant bacterial from 27.38% to 35.87% during COVID-19 (p<0.001), particularly in blood culture, cerebrospinal fluid, catheter, and pus. However, there was a non-significant change in puncture fluid, expectoration, protected distal sampling, joint fluid, stool culture, and genital sampling. A decrease in Multidrug-resistant bacteria (MDRB) was observed only in cytobacteriological urine tests (p<0.05). According to species, there was an increase in extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus. Conclusion: In our study, it is particularly noticeable that the MDRB has increased. These results highlight the importance that the pandemic has not been able to slow the progression.

A young child with acute perforated appendicitis due to Comamonas kerstersii: a rare case report.

Comamonas species are rarely associated with human infections. Recent reports found that Comamonas kerstersii was associated with severe diseases such as abdominal infection and bacteremia. However, Comamonas kerstersii may be confused with Comamonas testosteroni using the automatic bacterial identification systems currently available. An 8-year-old boy who had a right iliac fossa pain and classic migration of pain at the temperature of 38.9°C. The positive strain of aerobic and anaerobic bottles of blood cultures was identified. The patient was diagnosed as acute peritonitis and perforated appendix with abdominal abscess. The bacterium was identified by routine methods, MALDI-TOF-MS. The patient was treated with exploratory laparotomy, appendectomy, tube drainage, and prescribing antibiotic treatment. The patient was discharged with complete recovery. The organisms were confirmed as Comamonas kerstersii by MALDI-TOFMS and a combination of the other results. Our findings suggest that Comamonas kerstersii infection occurs most often in association with perforated appendix and bacteremia. We presume that Comamonas kerstersii is an opportunistic pathogen or commensal with the digestive tract and appendix bacteria.

Multidrug-Resistant Bacteria Isolated from Blood Culture Samples in a Moroccan Tertiary Hospital: True Bacteremia or Contamination?

Purpose: To demonstrate the relevance of clinico-biological correlation in the interpretation of positive blood cultures (BC) for multidrug-resistant (MDR) bacteria, among adult and pediatric patients, in order to distinguish between true bacteremia (TB) and contaminations and to evaluate the impact on patient management. Patients and Methods: This six-month study was conducted at Mohammed VI University Hospital in Marrakech. All MDR bacteria isolated from BCs carried out on hospitalized patients during this period were included. For each positive BC to MDR microorganism, demographic and clinical characteristics, laboratory findings, therapeutic and evolution data were collected. Results: TB was considered in 157 (94.6%) of the 166 positive-culture episodes for MDR bacteria, while 9 (5.4%) were classified as false-positive. Contamination rate was 0.2% (9/3824). TB and contaminations occurred mainly in intensive care units (ICUs), with the neonatal ICU being the most concerned (p = 0.016). Clinical signs of sepsis were present in all TB patients, with a significant difference between the two groups (p = 0.000). CRP values were higher in the TB group (p = 0.000). The most isolated true pathogens were ESBL-producing Enterobacterales (50%) and carbapenem-resistant Enterobacterales (33.3%). They also predominated in contaminated BCs. Isolation of the same microorganism from other sites was significantly associated with TB (p = 0.012). In contrast to the contaminations group, the difference in the clinical course of TB patients, according to whether or not they received appropriate probabilistic antibiotics, was statistically significant (p = 0.000). These patients had longer hospital stays and longer durations of antibiotic therapy. The overall mortality rate was 39.6%. Conclusion: Distinguishing between MDR-positive BCs representing clinically significant bacteremia or simple contamination requires a careful clinical, biological, and microbiological confrontation of each MDR positive BC in order to avoid unnecessary overuse of broad-spectrum antibiotics and thus reduce resistance selective pressure.

Expression analysis of mitotic spindle checkpoint genes in breast carcinoma: role of NDC80/HEC1 in early breast tumorigenicity, and a two-gene signature for aneuploidy.

BACKGROUND: Aneuploidy and chromosomal instability (CIN) are common abnormalities in human cancer. Alterations of the mitotic spindle checkpoint are likely to contribute to these phenotypes, but little is known about somatic alterations of mitotic spindle checkpoint genes in breast cancer. METHODS: To obtain further insight into the molecular mechanisms underlying aneuploidy in breast cancer, we used real-time quantitative RT-PCR to quantify the mRNA expression of 76 selected mitotic spindle checkpoint genes in a large panel of breast tumor samples. RESULTS: The expression of 49 (64.5%) of the 76 genes was significantly dysregulated in breast tumors compared to normal breast tissues: 40 genes were upregulated and 9 were downregulated. Most of these changes in gene expression during malignant transformation were observed in epithelial cells.Alterations of nine of these genes, and particularly NDC80, were also detected in benign breast tumors, indicating that they may be involved in pre-neoplastic processes.We also identified a two-gene expression signature (PLK1 + AURKA) which discriminated between DNA aneuploid and DNA diploid breast tumor samples. Interestingly, some DNA tetraploid tumor samples failed to cluster with DNA aneuploid breast tumors. CONCLUSION: This study confirms the importance of previously characterized genes and identifies novel candidate genes that could be activated for aneuploidy to occur. Further functional analyses are required to clearly confirm the role of these new identified genes in the molecular mechanisms involved in breast cancer aneuploidy. The novel genes identified here, and/or the two-gene expression signature, might serve as diagnostic or prognostic markers and form the basis for novel therapeutic strategies.

Epidemiology of Respiratory Pathogens in Children with Severe Acute Respiratory Infection and Impact of the Multiplex PCR Film Array Respiratory Panel: A 2-Year Study.

Sever acute respiratory infections (SARIs) are a public health issue that are common in children and are associated with an important morbidity and mortality rate worldwide. Although SARI are mainly caused by viruses, they are still a cause of antibiotic overuse. The use of molecular methods especially real-time multiplex PCR allowed to detect a wide range of respiratory viruses and their subtype as well as some atypical bacteria. The aim of this study was to investigate the epidemiology of respiratory pathogens detected in children admitted with SARI and to highlight the role of real-time multiplex PCR in the rapid diagnosis of viral and bacterial SARI. This work is a descriptive observational study from January 2018 to December 2019 including nasopharyngeal secretions collected from 534 children hospitalised in paediatric department. The detection of respiratory viruses and bacteria was performed by the FilmArray® Respiratory Panel. A total of 387 (72.5%) children were tested positive for at least one respiratory pathogen, and 23.3% of them were coinfected with more than one pathogen. Viral aetiology was found in 91.2% (n = 340). The most common viruses detected were HRV (n = 201) and RSV (n = 124), followed by PIV (n = 35) influenza A (n = 29) and human metapneumovirus (n = 27). Bacteria was found in 8.8% (n = 47), and Bordetella pertussis was the most detected. Respiratory syncytial virus and Bordetella pertussis were significantly higher in infants less than 6 months old. The detection of RSV and influenza A presented a pic in winter, and HMPV was statistically significant in spring (p < 0.01). This study described the epidemiology of respiratory pathogens involved in severe respiratory infections in children that were affected by several factors such as season and age group. It also highlighted the importance of multiplex PCR in confirming viral origin, thus avoiding irrational prescription of antibiotics in paediatric settings.

Multicentric MFI30 study: Standardization of flow cytometry analysis of CD30 expression in non-Hodgkin lymphoma.

CD30 transmembrane receptor, a member of the tumor necrosis factor receptor family, is expressed in different lymphomas. Brentuximab vedotin (BV), a CD30 monoclonal antibody (Ab)-drug conjugate, is effective in CD30-positive lymphomas. However, the response to BV is not always correlated to CD30 expression detected by immunohistochemistry (IHC). The objectives of this study were to standardize and evaluate CD30 intensity by flow cytometry (FCM) in non-Hodgkin's lymphomas. Twelve centers analyzed 161 cases on standardized cytometers using normalized median fluorescence intensity (nMFI30) of three different Abs, of which one clone can recognize the same epitope as BV. FCM distinguished four groups of cases: negative group (n = 110) which showed no expression with the three clones; high positive group (n = 13) which gave nMFI30 > 5% with all tested clones; dim positive group (n = 17) which showed nMFI30 > 1% with all tested clones and <5% for at least one; discordant group (n = 21) with positive and negative expression of the different clones. In consistency with the literature, CD30 was positive in all anaplastic large cell lymphomas, in some diffuse large B-cell lymphomas (DLBCL), and in other rare lymphomas. FCM results were concordant with those of IHC in 77% of cases. Discrepancies could be explained by clones-related differences, microenvironment, or intracytoplasmic staining. Interestingly, FCM was more sensitive than IHC in 11% of cases, especially in DLBCL. Multicenter standardized FCM of specific CD30 could improve case detection and extend the treatment of BV to various CD30-positive lymphomas.

Ex vivo effects of high-density lipoprotein exposure on the lipopolysaccharide-induced inflammatory response in patients with severe cirrhosis.

UNLABELLED: High-density lipoproteins (HDL) are known to neutralize lipopolysaccharide (LPS). Because patients with cirrhosis have lower HDL levels, this may contribute to LPS-induced ex vivo monocyte overproduction of proinflammatory cytokines. However, the effects of HDL on cytokine production by monocytes from patients with cirrhosis have never been studied. The aim of this study was to determine the effects of HDL on LPS-induced proinflammatory cytokine production in whole blood and isolated monocytes from patients with severe cirrhosis and controls. Plasma levels of HDL and cytokines were determined. The effects of reconstituted HDL (rHDL) on LPS-induced cytokine production in whole blood were assessed by cytokine array and on tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) production in isolated monocytes. Plasma HDL levels were significantly lower in patients with cirrhosis than in controls. Plasma levels of TNF-alpha and IL-6 were significantly higher in patients with cirrhosis than in controls. Incubation of rHDL with whole blood prevented LPS-induced TNF-alpha and IL-6 overproduction in patients with cirrhosis. LPS-induced TNF-alpha production and CD14 expression were significantly more marked in cirrhotic monocytes than in control monocytes, and both decreased significantly after rHDL incubation. LPS-induced down-regulation of scavenger receptor, class B, type I (SR-BI) expression was abolished in cirrhotic monocytes. CONCLUSIONS: This study shows that rHDL abolishes the LPS-induced overproduction of proinflammatory cytokines in whole blood from patients with severe cirrhosis. These results were confirmed in isolated monocytes from these patients. This suggests that administration of rHDL might be a useful strategy for the treatment of cirrhosis to limit LPS-induced cytokine overproduction.

[Severe thrombopenia as single sign of hemophagocytosis in a patient with cirrhosis and lethal infection of ascitis fluid by Escherichia coli]. / Thrombopénie sévère d'aggravation rapide comme seul signe d'une hémophagocytose chez un malade atteint de cirrhose avec infection léthale du liquide d'ascite par Escherichia coli.

Hemophagocytosis is defined by a systemic macrophages activation, phagocyting the blood elements. This syndrome can be primary or secondary to multiple causes such as neoplasia or infections. We report here the first case of a hemophagocytosis caused by an Escherichia coli infection of ascitis fluid.

How to facilitate early diagnosis of CNS involvement in malignant lymphoma.

INTRODUCTION: Making the diagnosis of secondary CNS involvement in lymphoma can be difficult due to unspecific signs and symptoms, limited accessibility of brain/myelon parenchyma and low sensitivity and/or specifity of imaging and cerebrospinal fluid (CSF) examination currently available. Areas covered: MRI of the total neuroaxis followed by CSF cytomorphology and flow cytometry are methods of choice when CNS lymphoma (CNSL) is suspected. To reduce the numerous pitfalls of these examinations several aspects should be considered. New CSF biomarkers might be of potential diagnostic value. Attempts to standardize response criteria are presented. Expert commentary: Diagnosing CNSL remains challenging. Until diagnostic methods combining high sensitivity with high specifity are routinely introduced, high level of awareness and optimal utilization of examinations currently available are needed to early diagnose this potentially devastating disease.