A chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. ...Reproducing a proliferative stimulation ex vivo is critical to decipher the mechanisms of leukemogenesis in these malignancies. However, functional studies of CLL cells remains limited since current ex vivo B cell receptor (BCR) stimulation protocols are not sufficient to induce the proliferation of these cells, pointing out the need of mandatory BCR co-factors in this process. Here, we investigated benefits of several BCR co-stimulatory molecules (IL-2, IL-4, IL-15, IL-21 and CD40 ligand) in multiple culture conditions. Our results demonstrated that BCR engagement (anti-IgM ligation) concomitant to CD40 ligand, IL-4 and IL-21 stimulation allowed CLL cells proliferation ex vivo. In addition, we established a proliferative advantage for ZAP70 positive CLL cells, associated to an increased phosphorylation of ZAP70/SYK and STAT6. Moreover, the use of a tri-dimensional matrix of methylcellulose and the addition of TLR9 agonists further increased this proliferative response. This ex vivo model of BCR stimulation with T-derived cytokines is a relevant and efficient model for functional studies of CLL as well as lymphoproliferative malignancies.
Because of chronic anemia, hypogonadotropic hypogonadism, and iron chelation, pregnancy in homozygous and heterozygous compound beta-thalassemia patients stays a challenge. Pregnancies of transfused ...beta-thalassemia women registered in the French National Registry, conducted between 1995 and 2015, are described. These pregnancies were compared with pregnancies in healthy women and to data previously published in the literature. Fifty-six pregnancies of 37 women were studied. There were 5 twin pregnancies. Assisted reproductive technologies (ART) were used in 9 pregnancies. Median term at delivery was 39 amenorrhea weeks, and median weight at birth was 2780 g. Cesarean section was performed in 53.6% of the pregnancies. There were 6 thromboembolic events, 6 serious infections, 6 pregnancy-induced hypertensions (PIH), 6 intrauterine growth retardations (IUGR), 5 severe hemorrhages, 4 gestational diabetes, 3 alloimmunizations, 2 heart diseases, and 1 pre-eclampsia. There were 5 infections and 4 osteoporosis in the first year of post-partum. ART and cesarean sections were more often used in the beta-thalassemia group, compared to control subjects. Thromboembolic events, PIH, hemorrhage at delivery, and IUGR were more frequent in the beta-thalassemia group. Time to delivery was not different, but infant weight at birth was significantly smaller in the beta-thalassemia group. In the post-partum period, global maternal complications were more frequent in the beta-thalassemia group. Pregnancy in transfused beta-thalassemia women is safe with rare obstetrical and fetal complications. Cesarean section remains often chosen, and infant weight at birth remains smaller than that in the general population, despite delivery at full term.
•Similar mortality for Scedosporium and Lomentospora-related infections in children.•Median time to death for children with Lomentospora-infections was less than a week.•Infection of the brain and ...blood were associated with high mortality.•Voriconazole administration and surgery for antifungal treatment improve survival.
Current knowledge on infections caused by Scedosporium spp. and Lomentospora prolificans in children is scarce. We therefore aim to provide an overview of risk groups, clinical manifestation and treatment strategies of these infections.
Pediatric patients (age ≤18 years) with proven/probable Scedosporium spp. or L. prolificans infection were identified in PubMed and the FungiScope® registry. Data on diagnosis, treatment and outcome were collected.
Fifty-five children (median age 9 years IQR: 5–14) with invasive Scedosporium spp. (n = 33) or L. prolificans (n = 22) infection were identified between 1990 and 2019. Malignancy, trauma and near drowning were the most common risk factors. Infections were frequently disseminated. Most patients received systemic antifungal therapy, mainly voriconazole and amphotericin B, plus surgical treatment.
Overall, day 42 mortality was 31%, higher for L. prolificans (50%) compared to Scedosporium spp. (18%). L. prolificans infection was associated with a shorter median survival time compared to Scedosporium spp. (6 days IQR: 3–28 versus 61 days IQR: 16–148). Treatment for malignancy and severe disseminated infection were associated with particularly poor outcome (HR 8.33 95% CI 1.35–51.40 and HR 6.12 95% CI 1.52–24.66, respectively). Voriconazole use at any time and surgery for antifungal treatment were associated with improved clinical outcome (HR 0.33 95% CI 0.11–0.99 and HR 0.09 95% CI 0.02–0.40, respectively).
Scedosporium spp. and L. prolificans infections in children are associated with high mortality despite comprehensive antifungal therapy. Voriconazole usage and surgical intervention are associated with successful outcome.
•Patients treated with ruxolitinib are at higher risk of mycobacterial infection.•Tuberculosis under ruxolitinib can occur without any prior tuberculosis.•Mycobacterial infections under ruxolitinib ...can occur early or late.
Ruxolitinib is a JAK-1/JAK-2 inhibitor indicated for the treatment of polycythemia vera and primary or secondary myelofibrosis. Only one patient (0.2%) was diagnosed with tuberculosis among the 485 patients receiving ruxolitinib in the four pivotal trials. Fourteen cases of tuberculosis have since been reported. We observed two (3%) mycobacterial infections (one due to Mycobacterium tuberculosis and one due to Mycobacterium avium complex) in our cohort of 65 patients receiving ruxolitinib. This observation suggests that the rate of mycobacterial infection might be higher than that observed in the pivotal trials and that atypical mycobacterial infections can also occur.
Invasive fungal infection (IFI) is a leading cause of infection-related mortality among patients with cancer and prolonged neutropenia and among allogeneic hematopoietic stem cell transplant ...recipients with graft-versus-host disease. Invasive candidiasis was the principal IFI in the period predating fluconazole prophylaxis, whereas today, invasive aspergillosis and other mold infections cause the majority of deaths from fungal infection in this patient population. The changing epidemiology of IFI, in addition to advances made in antifungal therapeutics and early diagnosis of IFI, warrant a reevaluation of earlier strategies aimed at prevention and early treatment of IFI that were developed several years ago. Here, we propose that persistent neutropenic fever is nonspecific for an IFI and should not be used as the sole criterion for empirical modification in the antifungal regimen in a patient receiving mold-active prophylaxis. We explore the potential benefits and gaps in knowledge associated with employing chest CT scans and laboratory markers as diagnostic adjuncts for IFI. Finally, we discuss the implications of newer antifungal agents and diagnostic adjuncts in the design of future clinical trials to evaluate prophylaxis and early prevention strategies.
Invasive mold infections (IMD) are an emerging concern due to the growing prevalence of patients at risk, encompassing but not limited to allogeneic hematopoietic stem cell transplant recipients, ...hematological malignancies patients, solid organ transplant recipients and intensive care unit patients. In contrast with invasive aspergillosis and mucormycosis, other hyalohyphomycoses and phaeohyphomycoses remain poorly known. We conducted a retrospective analysis of the clinical, biological, microbiological and evolutive features of 92 IMD having occurred in patients in our tertiary-care center over more than 25 years. A quarter of these infections were due to multiple molds. Molds involved were
spp. (36.2% of IMD with a single agent, 43.5% of IMD with multiple agents), followed by
spp. (respectively 14.5% and 26.1%) and
spp. (respectively 13.0% and 8.7%). Mortality at day 84 was higher for
spp.,
spp. or multiple pathogens IMD compared with
or other pathogens (51.7% vs. 17.6%,
< 0.05). Mortality at day 84 was also influenced by host factor: higher among hematology and alloHSCT patients than in other patients (30.6% vs. 20.9% at day 42 and 50.0% vs. 27.9% at day 84,
= 0.041). Better awareness, understanding and treatments are awaited to improve patient prognosis.
Cola beverage and delayed elimination of methotrexate Santucci, Raoul; Levêque, Dominique; Herbrecht, Raoul
BJCP. British journal of clinical pharmacology/British journal of clinical pharmacology,
November 2010, Letnik:
70, Številka:
5
Journal Article
Recenzirano
Odprti dostop
AIMS
To report a case of severe delayed methotrexate elimination attributable to consumption of a cola beverage.
METHODS
To investigate unexplained low urinary pH in a lymphoma patient treated with ...high‐dose methotrexate.
RESULTS
Unexpected urinary acidity, despite administration of large amounts of sodium bicarbonate, could be attributed to repeated consumption of a cola beverage. It resulted in a delayed elimination of methotrexate and acute renal failure. Discontinuation of cola drinks, increase in calcium folinate rescue and in sodium bicarbonate allowed satisfactory elimination of methotrexate on day 12 after infusion and recovery from renal impairment without other severe toxicity. No other cause of delay in methotrexate elimination could be identified.
CONCLUSIONS
Cola beverages have a low pH due to their phosphoric acid content that is excreted by renal route. We recommend patients receiving high dose methotrexate abstain from any cola drink within 24 h before and during methotrexate administration and until complete elimination of the drug.
Primary invasive cutaneous aspergillosis is a rare fungal infection that occurs mostly in immunocompromised patients. Newborns of very low birth weight present a high risk for this type of infection ...due to an immaturity of the cutaneous barrier and of the immune system.
We describe here a case of simultaneous invasive cutaneous aspergillosis in two preterm twins. Two male preterm bichorionic biamniotic twins (A & B) were born at a general hospital by spontaneous normal delivery at 24 weeks and 6 days of gestation. They were transferred to our hospital where they receive surfactant, antibiotics and hydrocortisone. Six days later, twin A showed greenish lesions in the umbilical region. The spectrum of antibiotic therapy was broadened and fluconazole was added. The umbilical catheters of the two twins were removed and replaced by epicutaneo-cava venous catheters and the cultures were positive for Aspergillus fumigatus. Fluconazole was replaced in both twins by liposomal amphotericin B and the incubators were changed. The serum galactomannan was also positive for both twins. At day 10, yellowish lesions appeared in the abdominal region in twin B. He died on day 18 following complications related to his prematurity. Concerning the twin A, serum galactomannan was negative on day 30; liposomal amphotericin B was stopped 1 week later, with a relay by econazole (cream). His condition improved and on day 66 he was transferred for follow-up at the general hospital where he was born.
The source of contamination by A. fumigatus was not identified, but other similar cases from the literature include construction work at or near the hospital, oximeter sensors, latex finger stalls, non-sterile gloves, humidifying chambers of incubators, bedding and adhesive tapes. The skin fragility of preterm newborns is an excellent potential entry point for environmental fungal infections. These cases highlight the importance of suspecting primary cutaneous aspergillosis in extremely low birth weight neonates with rapidly progressive necrotic lesions.
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