Cardiac involvement in pediatric hemolytic uremic syndrome.

BACKGROUND: Cardiac involvement is a known but rare complication of pediatric hemolytic uremic syndrome (HUS). We conducted a nationwide observational, retrospective case-control study describing factors associated with the occurrence of myocarditis among HUS patients. METHODS: Cases were defined as hospitalized children affected by any form of HUS with co-existent myocarditis in 8 French Pediatric Intensive Care Units (PICU) between January 2007 and December 2018. Control subjects were children, consecutively admitted with any form of HUS without coexistent myocarditis, at a single PICU in Lyon, France, during the same time period. RESULTS: A total of 20 cases of myocarditis were reported among 8 PICUs, with a mean age of 34.3 ± 31.9 months; 66 controls were identified. There were no differences between the two groups concerning the season and the typical, Shiga toxin-producing Escherichia coli (STEC-HUS), or atypical HUS (aHUS). Maximal leukocyte count was higher in the myocarditis group (29.1 ± 16.3G/L versus 21.0 ± 9.9G/L, p = 0.04). The median time between admission and first cardiac symptoms was of 3 days (range 0-19 days), and 4 patients displayed myocarditis at admission. The fatality rate in the myocarditis group was higher than in the control group (40.0% versus 1.5%, p < 0.001). Thirteen (65%) children from the myocarditis group received platelet transfusion compared to 19 (29%) in the control group (p = 0.03). CONCLUSION: Our study confirms that myocarditis is potentially lethal and identifies higher leukocyte count and platelet transfusion as possible risk factors of myocarditis. A higher resolution version of the Graphical abstract is available as Supplementary information.

Escherichia coli-associated hemolytic uremic syndrome and severe chronic hepatocellular cholestasis: complication or side effect of eculizumab?

BACKGROUND: Liver lesions of hemolytic uremic syndrome due to Shiga-toxin-producing Escherichia coli (STEC-HUS) are uncommon. CASE-DIAGNOSIS/TREATMENT: We report three observations of severe STEC-HUS with delayed hepatic involvement. They presented with multiple organ failure and received eculizumab; 15 days after the onset of STEC-HUS, cholestasis appeared and cytolysis worsened. Abdominal ultrasonography showed vesicular sludge. Liver biopsy performed 3 to 6 months after the STEC-HUS found cholangiolar proliferation and inflammatory portal fibrosis. Despite renal recovery, cholestasis persisted and worsened in two cases, leading to biliary cirrhosis and subsequent liver transplantation. Pathological examination of one native liver found thrombotic microangiopathy. CONCLUSIONS: Even though the pathological examination performed on one native liver demonstrated areas of thrombotic microangiopathy, we cannot completely rule out that eculizumab may have worsened the liver lesions. Before the efficacy of eculizumab in STEC-HUS is formally demonstrated, physicians should stay cautious in its use.

Rescue of Pap-Mas in Systemic JIA Using Janus Kinase Inhibitors, Case Report and Systematic Review.

INTRODUCTION: Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1ß represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as potential risk factors. We report on a new case with longitudinal immunomonitoring successfully treated by Janus Kinase inhibitors (JAKi) and review past clinical descriptions of this new entity. METHODS: We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment. RESULTS: Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-γ or IL-1ß/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis. CONCLUSIONS: JAKi represent a promising option in the treatment of lung disease associated with sJIA.

Chronic kidney disease consecutive to chemotherapy for chondroblastic osteosarcoma: A report on 6 pediatric cases.

BACKGROUND: The management of osteosarcoma in children and adolescents is based on poly-chemotherapy including several nephrotoxic drugs (e.g. ifosfamide, methotrexate, and cisplatinum). Chronic renal toxicity is a frequent complication but stage 5 chronic kidney disease requiring dialysis is rare. We report here a series of six pediatric patients with osteosarcoma displaying chronic kidney disease after chemotherapy. CASE-DIAGNOSIS/TREATMENT: We retrospectively reviewed the medical charts, mainly for clinical history, timing between chemotherapy and development of tubulopathy and CKD, type of therapies and global evolution (chronic dialysis and further renal transplantation, n=2; death, n=1). Notably, all patients suffered from chondroblastic osteosarcoma. CONCLUSIONS: Advanced chronic kidney disease can be a complication of osteosarcoma management that could more frequently lead to dialysis and further transplantation. It would be interesting to identify specific risk factors of such renal toxicity. The chondroblastic sub-type may be associated with such susceptibility, but this needs to be confirmed.

The addition of hormone therapy to tamoxifen does not prevent hot flashes in women at high risk for developing breast cancer.

Tamoxifen significantly reduces the risk of developing breast cancer in women at increased-risk. The usefulness of tamoxifen has been limited by its side effect profile, especially its propensity to worsen vasomotor symptoms. Hormone therapy (HT) has long been utilized to reduce vasomotor symptoms in peri- and post-menopausal women. The aim of this study was to compare the incidence of hot flashes, weight gain and other side effects associated with taking tamoxifen alone versus tamoxifen in combination with HT in high-risk women. One hundred eighty high-risk women were enrolled into one of two parallel study cohorts to receive tamoxifen alone (93 women) or tamoxifen with HT (87 women). Women were monitored at baseline, 3 months and then yearly for assessments of menopausal symptoms and toxicities associated with tamoxifen alone versus tamoxifen plus HT. We also assessed for differences in menopausal symptoms and toxicities by type of HT (estrogen vs. estrogen and progestin combination). Hot flash scores increased at 3 months and at 1 year compared with baseline in women on tamoxifen alone as well as for women on HT. Women on tamoxifen with estrogen only replacement had the greatest increase in hot flash scores, although this was not significantly different than the increase seen with tamoxifen alone. About 47% of participants on tamoxifen gained weight and there was a strong trend towards less weight gain in women on the combination of tamoxifen and HT, most pronounced for those on tamoxifen with estrogen alone replacement therapy. The addition of HT to tamoxifen therapy does not ameliorate tamoxifen-induced vasomotor symptoms. Tamoxifen associated weight gain, however, may be lessened by the addition of HT.

Cytomegalovirus infection in the first year after pediatric kidney transplantation.

Cytomegalovirus is common in adult recipients (prevalence of 40-90%). Children are typically seronegative but immunosuppression may prone to primary-infection or viral reactivation, with potentially severe consequences. CMV infection incidence in pediatric kidney transplant recipients has seldom been investigated. The aim of our study was to evaluate the incidence and timing of CMV infection during the first year after renal transplantation. We assembled a retrospective cohort of 136 children who had received a kidney transplant between 2003 and 2014 with a year follow-up. The patients were classified regarding CMV infection as high risk (D+/R-), intermediate risk (R+) or low risk (D-/R-). CMV infection was defined by the viral replication remaining asymptomatic whereas CMV disease concerned viral replication with clinical and/or biological symptoms. Oral valganciclovir was used as prophylaxis for high-risk recipients. A total of 38 patients (27.9%) developed CMV infection, 13 (40.6%) of the 32 D+/R-, 24 (45.3%) of the 53 R+ and 1 (2.0%) of the 51 D-/R-. Of these 38 infected patients, 10 developed tissue-invasive disease. During the first year after kidney transplantation, 27.9% of recipients developed CMV infection. This study confirms the influence of donor and recipient CMV status on infection propensity and highlights the importance of adequate follow-up for intermediate risk patients.

[Use of hypnosis in radiotherapy as an alternative to general anesthesia in pediatric radiation oncology]. / Radiothérapie des enfants de moins de cinq ans : peut-on limiter les anesthésies itératives par les rituels et l'hypnose ?

BACKGROUND: General anesthesia (GA) is often needed for radiotherapy (RT) in young children. This study aimed to evaluate the place of the rituals and/or hypnosis in pediatric in a reference center in pediatric radiation oncology in Rhône-Alpes Auvergne. METHODS: This observational study retrospectively collected data on AG in children<5 years treated by RT in Leon-Berard regional center, Lyon, France between 2003 and 2014. Two-time periods, before and after 2008 have been compared, the second one introducing accompaniment methods such as hypnosis systematically. Explanatory analyses of AG were performed using logistic regression. RESULTS: One hundred and thirty-two children benefited from RT in that period and were included (70 patients until 2008, 62 after 2008). Fifty-three percent were irradiated under GA. There was significant reduction (P<0.1) in the use of GA after 2008. The use of GA was not significantly associated with the RT techniques. The patients more likely to undergo RT without GA were the oldest and the patients treated for abdominal lesions (P<0.01). DISCUSSION: The study confirms that rituals and hypnosis can be used instead of GA in about half of patients under 5 years, even also with high-technicity RT requiring optimal immobilization.