Management of Enteral Feeding and Application of Probiotics in Very Low Birth Weight Infants - A National Survey in German NICUs.

BACKGROUND: The advantage of breast milk feeding, and supplementation of probiotics is well known and proven. However, the lack of reliable amounts of colostrum and/or transient breast milk during the first few postnatal days might inhibit timely enteral nutrition. METHODS: The aim of this nationwide survey in German Level-1 neonatal intensive care units (NICUs) was to collect data regarding the management of feeding in the first days of life in very low birth weight infants (VLBWIs, birth weight<1500 g). In addition, we analyzed differences in the use of probiotics. An online survey was sent to all 163 Level-1 NICUs in Germany. RESULTS: 110/163 (67.5%) hospitals participated in our study. One-fifth of all participants used exclusively breast milk. The reported incidence of necrotizing enterocolitis (NEC) was lower in NICUs that exclusively used breast milk in VLBWIs (p=0.08). Two-thirds start enteral feeding independent of gestational age during the first 12 hours postnatally with either breast milk or formula. 80% of all participants checked gastric residuals routinely. The use of probiotics differs widely concerning duration and interruption during antibiotic therapy. CONCLUSION: The exclusive use of breast milk is associated with a lower incidence of NEC. The result of our survey emphasizes the paramount importance of nutrition with mother`s milk. In case of insufficient availability of mother`s milk, the use of human donor milk still appears to be superior to formula feeding. The implementation of human donor milk banks should therefore be promoted.

Management of prolonged meconium evacuation in preterm infants: A survey-based analysis in German Neonatal Intensive Care Units.

AIM: Due to the functional immaturity of bowel motility, a delayed passage frequently requires evacuation of meconium in preterm infants. Often rectal enemas and oral laxatives are used to manage these bowel evacuation disorders. METHODS: An online survey was sent to all 163 high-level Neonatal Intensive Care Units (NICUs) in Germany. The participants were queried on rectal enemas, laxative therapy and outcome incidences. RESULTS: A total of 110/163 (67.5%) hospitals participated in the study. 103/110 (93.6%) participating sites applied rectal enemas in cases of delayed meconium evacuation and 63/110 (57.3%) additionally used oral laxatives. In total, 15 different solutions and 7 different application systems were used for rectal instillation. Preterm infants receiving enemas within the first 48 hours after birth were found to have a significantly lower incidence of FIP (p = 0.006). Altogether 8 different oral laxatives were utilised. CONCLUSION: Therapeutic approaches to the management of prolongated meconium evacuation differ widely among German NICUs. Our survey highlights the diversity of applied substances, means of application and differences in duration and frequency of interventions. Macrogol was commonly used in neonates as an oral laxative despite the lack of approval from the manufacturer.

High Levels of Morbidity and Mortality Among Pediatric Hematopoietic Cell Transplant Recipients With Severe Sepsis: Insights From the Sepsis PRevalence, OUtcomes, and Therapies International Point Prevalence Study.

OBJECTIVES: Pediatric severe sepsis is a major cause of morbidity and mortality worldwide, and hematopoietic cell transplant patients represent a high-risk population. We assessed the epidemiology of severe sepsis in hematopoietic cell transplant patients, describing patient outcomes compared with children with no history of hematopoietic cell transplant. DESIGN: Secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study, comparing demographics, sepsis etiology, illness severity, organ dysfunction, and sepsis-related treatments in patients with and without hematopoietic cell transplant. The primary outcome was hospital mortality. Multivariable logistic regression models were used to determine adjusted differences in mortality. SETTING: International; 128 PICUs in 26 countries. PATIENTS: Pediatric patients with severe sepsis prospectively identified over a 1-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In patients with severe sepsis, 37/567 (6.5%) had a history of hematopoietic cell transplant. Compared with patients without hematopoietic cell transplant, hematopoietic cell transplant patients had significantly higher hospital mortality (68% vs 23%; p < 0.001). Hematopoietic cell transplant patients were more likely to have hospital acquired sepsis and had more preexisting renal and hepatic dysfunction than non-hematopoietic cell transplant patients with severe sepsis. History of hematopoietic cell transplant, renal replacement therapy, admission from inpatient floor, and number of organ dysfunctions at severe sepsis recognition were independently associated with hospital mortality in multivariable analysis; hematopoietic cell transplant conferred the highest odds of mortality (odds ratio, 4.00; 95% CI, 1.78-8.98). In secondary analysis of hematopoietic cell transplant patients compared with other immunocompromised patients with severe sepsis, history of hematopoietic cell transplant remained independently associated with hospital mortality (odds ratio, 3.03; 95% CI, 1.11-8.27). CONCLUSIONS: In an international study of pediatric severe sepsis, history of hematopoietic cell transplant is associated with a four-fold increased odds of hospital mortality after adjustment for potential measured confounders. Hematopoietic cell transplant patients more often originated from within the hospital compared to children with severe sepsis without hematopoietic cell transplant, possibly providing an earlier opportunity for sepsis recognition and intervention in this high-risk population.

Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial.

PURPOSE: We prospectively studied the efficacy of high dose therapy (HDT) versus an oral maintenance treatment (OMT) in patients with stage IV soft tissue sarcoma (STS). PATIENTS AND METHODS: Both groups were pretreated with the CEVAIE combination consisting of carboplatin, etoposide, vincristine, actinomycin D, ifosfamide, and epirubicin. HDT consisted of a tandem cycle of thiotepa (600 mg/m(2)) plus cyclophosphamide (4,500 mg/m(2)) and melphalan (120 mg/m(2)) plus etoposide (1,800 mg/m(2)). This treatment was compared with OMT, consisting of four cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus etoposide (10 days 2 x 25 mg/m(2)/day), and 4 cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus idarubicin (10 days 4 x 5 mg/m(2)). Eligibility criteria were: diagnosis confirmed by reference pathology, primary stage IV, below 22 years of age, and having completed the study therapy. RESULTS: From 96 patients 45 were treated with HDT and 51 with OMT. The main risk parameters were equally distributed in both arms. After a median follow-up of 57.4 months, 11/45 (24.4%) patients in the HDT-arm and 26/51 (57.8%) patients in OMT-arm were alive. Kaplan-Meier analysis demonstrated an overall survival for the whole group of 0.27 (OMT group: 0.52, HDT group 0.27, log rank P = 0.03). The proportional hazard analysis for patients with rhabdomyosarcoma (RMS) or "RMS-like" tumors (77.1% of all patients) demonstrated an independent benefit of OMT on outcome. CONCLUSION: Oral maintenance therapy seems to be a promising option for patients with RMS-like stage IV tumors.

Rhinocerebral zygomycosis in a young girl undergoing allogeneic stem cell transplantation for severe aplastic anaemia.

We report on a 10-year-old girl with severe aplastic anaemia who developed rhinocerebral infection caused by Absidia corymbifera and a possible co-infection caused by Alternaria alternata. Despite prolonged neutropenia, therapy with liposomal amphotericin B and posaconazole improved the clinical condition. Subsequently, the girl underwent allogeneic haematopoietic stem cell transplantation (HSCT) for the underlying disease, but the fungal infection remained under control with the antifungal treatment. No severe side effect of the antifungal drugs was noted. Unfortunately, the girl died 5 months after HSCT due to disseminated adenovirus infection.

In lymphatic cells par-4 sensitizes to apoptosis by down-regulating bcl-2 and promoting disruption of mitochondrial membrane potential and caspase activation.

Inhibition of apoptosis is a hallmark of malignancies of the hematopoetic system. Previous studies in nonhematopoetic cells demonstrated that the prostate-apoptosis-response-gene-4 (Par-4) is up-regulated in cells undergoing programmed cell death and that Par-4 exerts its proapoptotic effect by down-regulating Bcl-2. After showing the aberrant expressional pattern of Par-4 in neoplastic lymphocytes as well as demonstrating inverse expressional patterns of Par-4 and Bcl-2 in malignant cells of patients suffering from acute lymphocytic leukemia, we assessed the functional consequences of Par-4 overexpression during apoptosis in Jurkat T lymphocytes. We show that in lymphatic cells Par-4 overexpression decreases the level of Bcl-2, whereas Bax, the proapoptotic counterpart of Bcl-2, retains unaltered levels. Moreover, Par-4 overexpression is accompanied by cleavage of poly(ADP-ribose) polymerase (PARP). Despite these effects, overexpression of Par-4 alone is not sufficient to induce apoptosis but markedly increases the rate of apoptosis on treatment with different chemotherapeutic agents. On chemotherapeutic treatment Par-4 overexpression enhances disruption of mitochondrial membrane potential, PARP-cleaving activity, as well as activation of caspase-3. The hypothesis of caspase-dependency of Par-4-promoted apoptosis is additionally supported by demonstrating complete abrogation of programmed cell death after pretreatment with a broad spectrum caspase-inhibitor. On inhibition of caspase-3 overexpression of Par-4 enables lymphatic cells to alternatively activate caspases-9, -6, and -7 by diminishing the influence of the inhibitors of apoptosis proteins (IAPs) cIAP1 and XIAP. Our study is the first to identify Par-4 as a proapoptotic protein in lymphatic cells, outlining a model of action evaluating the role of Bcl-2/Bax, as well as demonstrating the impact of Par-4 expression on PARP cleavage, disruption of mitochondrial membrane potential, caspase activation, and interactions with inhibitors of apoptosis proteins.