Current management of late onset neonatal bacterial sepsis in five European countries

Late onset neonatal sepsis (LOS) has a high mortality and the optimal management is poorly defined. We aimed to evaluate new expert panel-derived criteria to define LOS and characterize the current management and antibiotic susceptibility of LOS-causing organisms in Europe. A prospective observational study enrolled infants aged 4 to 90 days in five European countries. Clinical and laboratory findings as well as empiric treatment were recorded and patients were followed until the end of antibiotic therapy. Failure was defined as a change of primary antibiotic, no resolution of clinical signs, appearance of new signs/pathogens or death. Antibiotic therapy was considered appropriate if the organism was susceptible to at least one empiric antibiotic. 113 infants (median age 14 days, 62 % ≤1500 g) were recruited; 61 % were culture proven cases (28 CoNS, 24 Enterobacteriaceae, 11 other Gram-positives and 6 Gram-negative non-fermentative organisms). The predictive value of the expert-panel criteria to identify patients with a culture proven LOS was 61 % (95 % CI 52 % to 70 %). Around one third of Enterobacteriaceae were resistant to ampicillin + or cefotaxime + gentamicin but only 10 % to meropenem. Empiric treatment contained a total of 43 different antibiotic regimens. All-cause mortality was 8 % with an additional 45 % classified as failure of empiric therapy, mainly due to change of primary antibiotics (42/60). Conclusions: The expert panel—derived diagnostic criteria performed well identifying a high rate of culture proven sepsis. Current management of LOS in Europe is extremely variable suggesting an urgent need of evidence-based guidelines.     

Relapse in medulloblastoma: what can be done after abandoning high-dose chemotherapy? A mono-institutional experience

Purpose

We retrospectively report strategies used for medulloblastoma patients progressing after craniospinal irradiation where we aimed for: symptom control, a satisfactory quality of life, accrual in phase 1–2 trials, when available, and the first two conditions could no longer be satisfied by already experienced second-line strategies.

Methods

Surgery was used in cases of doubtful relapse or when only one site was affected. Radiotherapy was given whenever possible, especially to relieve symptoms. The main chemotherapy regimens were oral temozolomide/etoposide, intravenous (iv.) cisplatin/etoposide, iv. gemcitabine/oxaliplatin, an oral sonic hedgehog pathway inhibitor and oral melphalan.

Results

Between 1998 and 2011, we treated 18 patients relapsed after median 20 months. Nine had relapsed locally, four had dissemination, three single metastases, and two had one synchronous local and metastatic recurrence. Responses to chemotherapy were seen in 32 % of cases. The median hospital stay for treatments/complications was 19 days. The 1- and 3-year progression-free survival (PFS) rates were 28?±?10 % and 0 %, respectively, for OS, they were 44?±?12 % and 22?±?10 % but no patient was cured. The median PFS after a first relapse was 7 months (range 1–29); the median OS was 7 months (range 4–44). No patients died due to treatment toxicity. Late recurrence (more than 1–2 years after diagnosis) and involvement of single sites were favorable prognostic factors.

Conclusions

Without succeeding in patients cure, we ensured them further treatment with short hospital stay thus affording low personal and social costs. The chances of cure may emerge from tailored therapies according to genetic stratification.     

Modern management of phagocyte defects

Phagocytic neutrophil granulocytes are among the first immune cells active at sites of infection, forming an important first‐line defense against invading microorganisms. Congenital immune defects concerning these phagocytes may be due to reduced neutrophil numbers or function. Management of affected patients depends on the type and severity of disease. Here, we provide an overview of causes and treatment of diseases associated with congenital neutropenia, as well as defects of the phagocytic respiratory burst.     

Severe Hypoglycemia During Successful Treatment of Diffuse Hemangiomatosis with Propranolol

Abstract: A 27‐day‐old male infant with diffuse hemangiomatosis of the skin and liver was treated with oral propranolol at a dosage of 2 mg/kg per day. Five months later skin and liver hemangiomas regressed almost completely. After 160 days of onset of propranolol, the patient presented with seizures on waking up. Laboratory examinations showed blood glucose of 15 mmol (n.v. 50–110) and increased ketone bodies. Propranolol was recommenced at a lower dosage the day after the crisis and then withdrawn when the baby was aged ten months. Hypoglycemia is the most frequent and insidious side effect of propranolol, mainly occurring in circumstances with diminished oral intake. Although the risk appears small, increased vigilance for hypoglycemia in children on chronic propranolol treatment who have decreased caloric intake for any reason seems prudent.     

Multiple mechanisms of telomere maintenance exist and differentially affect clinical outcome in diffuse malignant peritoneal mesothelioma

PURPOSE: This study aims to investigate the prevalence of the two known telomere maintenance mechanisms, telomerase activity (TA) and alternative lengthening of telomeres (ALT), and to assess their prognostic relevance in diffuse malignant peritoneal mesothelioma (DMPM). EXPERIMENTAL DESIGN: In 44 DMPM specimens obtained from 38 patients, TA was determined using the telomeric repeat amplification protocol and ALT was detected by assaying ALT-associated promyelocytic leukemia nuclear bodies. The prognostic significance of telomere maintenance mechanisms was analyzed by Cox regression in the overall series and in a subset of 29 patients who underwent a uniform treatment regimen consisting of cytoreductive surgery and hyperthermic i.p. chemotherapy. RESULTS: Telomere maintenance mechanisms were detectable in 86.4% of DMPM: ALT or TA alone was found in 18.2% or 63.6% of lesions, respectively, whereas two cases (4.6%) were ALT+/TA+. TA and ALT proved to be inversely associated (P = 0.002). In the overall series, TA was prognostic for 4-year relapse (TA+ versus TA-, hazard ratio, 3.30; 95% confidence interval, 1.23-8.86; P = 0.018) and cancer-related death (TA+ versus TA-, hazard ratio, 3.56; 95% confidence interval, 1.03-12.51; P = 0.045), whereas ALT failed to significantly affect clinical outcome. These results held true also in the subset of patients submitted to uniform treatment with cytoreductive surgery and hyperthermic i.p. chemotherapy. CONCLUSIONS: Our results indicate that both known telomere maintenance mechanisms, TA and ALT, are present in DMPM and differentially affect patient prognosis.     

Chlamydia infection and lymphomas: association beyond ocular adnexal lymphomas highlighted by multiple detection methods

PURPOSE: Chlamydia psittaci (Cp) has been associated to ocular adnexal lymphomas (OAL) with variable geographic distribution. Herein, we used multiple Chlamydia detection tools to identify Cp elementary bodies-containing cell and to assess Cp prevalence in both nodal and extranodal lymphomas. EXPERIMENTAL DESIGN: TETR-PCR, immunohistochemistry, immunofluorescence, electron microscopy, and laser-capture microdissection were done in 35 OALs to define their effect in Chlamydia detection and, moreover, to identify the Cp cellular carrier. Cp prevalence was screened by TETR-PCR in 205 extraorbital lymphomas and 135 nonneoplastic controls. RESULTS: Twenty-six (74%) OALs were associated with Cp infection: immunohistochemistry, immunofluorescence, and laser-capture microdissection-assisted PCR showed that monocytes/macrophages were the Cp carriers; electron microscopy showed the presence of intact Cp elementary bodies into these cells. Immunohistochemistry and TETR-PCR showed a 70% concordance rate (P = 0.001). Cp DNA was equally prevalent in non-OAL, nodal, and extranodal lymphomas: among the latter, it was more common in diffuse large B-cell lymphomas of the skin (P = 0.03) and Waldeyer's ring. CONCLUSIONS: This multiparametric approach shows, for the first time, that monocytes/macrophages are the carriers of Cp, Cp seems preferentially associated with lymphomas arising in organs primarily exposed to antigens. The clinical implications of these findings deserve to be prospectively investigated.