History and Outcome of Febrile Neutropenia Outside the Oncology Setting: A Retrospective Study of 76 Cases Related to Non-Chemotherapy Drugs

International audienceBACKGROUND: Despite major advances in its prevention and treatment, febrile neutropenia remains a most concerning complication of cancer chemotherapy. Outside the oncology setting, however, only few data are currently available on febrile neutropenia related to non-chemotherapy drugs. We report here data on 76 patients with febrile neutropenia related to non-chemotherapy drugs, followed up in a referral center within a university hospital. PATIENTS AND METHODS: Data from 76 patients with idiosyncratic drug-induced febrile neutropenia were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis conducted at the Strasbourg University Hospital (Strasbourg, France). RESULTS: Mean patient age was 52.2 years old (range: 18-93) and gender ratio (F/M) 1.6, with several comorbidities present in 86.8% of patients. The most common causative drugs were: antibiotics (37.4%), antithyroid drugs (17.2%), neuroleptic and anti-epileptic agents (13.1%), non-steroidal anti-inflammatory agents and analgesics (8%), and platelet aggregation inhibitors (8%). Main clinical presentations upon hospitalization included isolated fever (30%), sore throat, acute tonsillitis and sinusitis (18.4%), documented pneumonia (18.4%), septicemia (14.5%), and septic shock (6.6%). Mean neutrophil count at nadir was 0.13 × 10(9)/L (range: 0-0.48). While in hospital, 22 patients (28.9%) worsened clinically and required intensive care unit placement. All patients were promptly treated with broad-spectrum antibiotics, and 45 (59.2%) with hematopoietic growth factors. Mean duration of hematological recovery (neutrophil count ≥1.5 × 10(9)/L) was 7.5 days (range: 2-21), which was reduced to 0.7 days (range: 2-16) (p = 0.089) with hematopoietic growth factors. Outcome was favorable in 89.5% of patients, whereas eight died. CONCLUSIONS: Like in oncology and myelosuppressive chemotherapy settings, idiosyncratic febrile neutropenia is typically serious, about 40% of patients exhibiting severe pneumonia, septicemia, and septic shock, with a mortality rate of 10%. Like in febrile, chemotherapy-related neutropenia, modern and timely management (immediate broad spectrum antibiotherapy, hematopoietic growth factors) may reduce infection-related mortality. All practitioners should be aware of this potential side-effect that may even occur in the event of "daily medication" exposur

Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia

BACKGROUND: Refractory hypoglycemia in patients with metastatic insulinoma is an important cause of morbidity and mortality. Everolimus could be a new therapeutic option. METHODS: Within the French Group, we conducted a retrospective, multicentric study of endocrine tumors to evaluate the time to the first recurrence of symptomatic hypoglycemia, after everolimus initiation, in patients with metastatic insulinoma and refractory hypoglycemia. Ongoing hyperglycemic medical options, tumor response, and safety information were recorded. RESULTS: Twelve patients with metastatic insulinoma and refractory hypoglycemia who were treated with everolimus between May 2007 and June 2011 were reviewed. Everolimus (starting dose, 10 mg/day, except in one patient, 5 mg/day) was given after a median of four previous therapeutic lines. Medication aimed at normalizing blood glucose levels in 11 patients. After a median duration of 6.5 months (range 1-35+ months), median time to the first recurrence of symptomatic hypoglycemia was 6.5 months (range 0 to 35+ months). Three patients discontinued everolimus because of cardiac and/or pulmonary adverse events at 1, 1.5, and 7 months after initiation, which led to two deaths. Three patients discontinued everolimus because of tumor progression at 2, 3, and 10 months after initiation, without recurrence of hypoglycemia. CONCLUSION: Everolimus appears to be a new effective treatment for patients with metastatic insulinoma and refractory hypoglycemia. Tolerance should be carefully monitored

A new specific succinate-glutamate metabolomic hallmark in SDHx-related paragangliomas

Paragangliomas (PGLs) are frequently associated with germline mutations in genes involved in energy metabolism. The purpose of the present study was to assess whether the tumor metabolomic profile of patients with hereditary and apparently sporadic PGLs enables the distinction of different subtypes of tumors. Twenty-eight unrelated patients with a histological diagnosis of PGLs were included in the present study. Twelve had germline mutations in SDHx genes (5 SDHB, 7 SDHD), 6 VHL, and 10 were apparently sporadic. Intact tumor samples from these patients (one per patient) were evaluated with (1)H high-resolution magic angle spinning (HRMAS) NMR spectroscopy. SDHx-related tumors were characterized by an increase in succinate levels in comparison to other tumor subtypes (p = 0.0001 vs VHL and p = 0.000003 vs apparently sporadic). Furthermore, we found significantly lower values of glutamate in SDHx-related tumors compared to other subtypes (p = 0.0007 vs VHL and p = 0.003 vs apparently sporadic). Moreover, SDHx-tumors also exhibited lower values of ATP/ADP/AMP (p = 0.01) compared to VHL. VHL tumors were found to have the highest values of glutathione (GSH) compared to other tumors. Based on 4 metabolites (succinate, glutamate, GSH, and ATP/ADP/AMP), tumors were accurately distinguished from the other ones on both 3- and 2-class PLS-DA models. The present study shows that HRMAS NMR spectroscopy is a very promising method for investigating the metabolomic profile of various PGLs. The present data suggest the existence of a specific succinate-glutamate hallmark of SDHx PGLs. The relevance of such a metabolomic hallmark is expected to be very useful in designing novel treatment options as well as improving the diagnosis and follow-up of these tumors, including metastatic ones

Manifestations rare d' allure auto-immune après allogreffe de moelle osseuse (à propos de 9 cas)

STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSTRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Stratégies diagnostiques et thérapeutiques des hyponatremies en médecine interne (étude rétrospective sur 90 patients)

STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les hypophysites primitives de l'adulte (à propos d'un cas.)

STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation de l'éducation thérapeutique aux anti-vitamines K de patients porteurs de valves mécaniques cardiaques (étude rétrospective menée au centre Lalance de 2006 à 2009)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

Les microparticules procoagulantes dans l'obésité (contribution à l'étude des complications thrombotiques artérielles et veineuses)

STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSTRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Retentissement de la grossesse dans l'angio-oedème héréditaire de type I, II et III (Etude rétrospective multicentrique de 63 patientes et 126 grossesses)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF