Pediatric severe factor XI deficiency: A multicenter study.

BACKGROUND: Factor XI (FXI) deficiency is a rare autosomal recessive bleeding disorder. Only scarce publications address its clinical features in children. The increased prevalence of FXI deficiency in Israel enabled data collection for this large multicenter cohort study. OBJECTIVE: Some hemostatic challenges may be unique or more common in children, such as bleeding in the neonatal period or trauma-related injury. The current study was designed to explore the potential impact of these differences in children with severe FXI deficiency. METHODS: Medical files of all children with FXI level under 15% followed at five tertiary centers were evaluated. The retrieved data comprised demographic and clinical characteristics, including bleeding episodes, surgical interventions, treatment strategies, as well as laboratory features. RESULTS: Sixty children, whose median age at diagnosis was 4.2 years and their median FXI level was 4%, were included. Three children experienced triggered intracranial hemorrhage (ICH) and two children had major bleeds. No bleeding complications occurred in surgeries in which hemostatic treatment consisting mostly of tranexamic acid or fresh frozen plasma was applied (n = 45). In contrast, excessive bleeding was noted in 25% of surgical procedures performed without hemostatic preparation (p = .002). CONCLUSION: This study's findings confirm the generally favorable outcome of this rare bleeding disorder, with no spontaneous bleeds or cases of perinatal ICH. Nonetheless, proper diagnosis and adequate hemostasis in the surgical setting are imperative. Unlike previous studies in adults, our pediatric study suggests an association between the severity of FXI deficiency and bleeding tendency.

Factor VII Deficiency in Patients Receiving Chronic Packed Cell Transfusions.

Acquired factor VII deficiency is a rare coagulopathy that has not been reported in transfusion-dependent patients so far. In this study, we reviewed files of 26 transfusion-dependent patients for coagulation profiles, factor V levels, factor VII levels, possible environmental factors influencing factor VII levels, and bleeding history. In 26 of 29 patients (89.6%), we found mild factor VII deficiency (<60%) with levels ranging between 35% and 56%. Bleeding history was unremarkable. We concluded that transfusion-dependent patients may have mild factor VII deficiency with no bleeding tendency under physiologic conditions.

The etiologic, microbiologic, clinical and outcome characteristics of immunocompetent young children <2 years of age hospitalized with acute neutropenia.

BACKGROUND: To describe the etiologic, microbiologic, clinical and outcome characteristics of acute neutropenia (absolute neutrophil count, ANC, <1.5 × 109/L) in hospitalized immunocompetent children. METHODS: Serious bacterial infections (SBI) were defined as culture-positive blood, urine, cerebrospinal fluid, articular fluid or stool infections, alveolar pneumonia, Brucellosis and Rickettsiosis. RESULTS: 431/671 (64.2%) healthy infants and children hospitalized with acute neutropenia were <2 years of age; 176 (40.8%), 167 (38.8%) and 88 (20.4%) patients were aged 0-3, 4-12 and 13-24 months, respectively. There were 19 (4.4%), 53 (12.3%), 140 (32.5%) and 209 (50.8%) patients with ANC count <200, 200-500, 501-1000 and 1001-1500 × 109 cells/L, respectively. Severe neutropenia (<500 × 109/L) was recorded in 72 (16.7%) patients. Fever >38 °C was present in 208/431 (48.3%) patients. Blood cultures were positive in 10 (2.3%), with Brucella melitensis, Staphylococcus aureus and Enterobacter spp. identified in 4, 3 and 2 patients, respectively; 5/10 patients with positive blood cultures were <3 months of age. Overall, 55/431 (12.7%) and 65/431 (15.1%) patients were diagnosed with SBIs and bacterial infections, respectively. Nasal washings-PCR for respiratory viruses was positive in 139/293 (47.4%) patients tested. An infectious etiology (bacterial and/or viral) was diagnosed in 190/431 (44.1%) patients. Three patients were diagnosed with acute lymphocytic leukemia. Resolution of neutropenia was achieved in 111/208 (53.4%) evaluable patients (63%, 50.6% and 48% of patients aged 0-3, 4-12 and >12 months, respectively and 56.8%, 53.5% and 52% of patients with severe, moderate and mild neutropenia, respectively). CONCLUSION: Acute neutropenia is common in immunocompetent children <2 years of age and is frequently associated with viral infections. We showed a substantial involvement of bacterial infections and particularly SBIs in the etiology of acute neutropenia. After a 1-month follow-up, resolution of neutropenia occurred in half of the patients, without association with age subgroups and with neutropenia severity.

Comparison of the etiologic, microbiologic, clinical and outcome characteristics of febrile vs. non-febrile neutropenia in hospitalized immunocompetent children.

We compared the etiologic, microbiologic, clinical, and outcome picture among febrile and non-febrile immunocompetent children hospitalized during 2013-2015 with acute neutropenia (absolute neutrophil count < 1.5 × 109/L). Serious bacterial infections (SBI) were defined as culture-positive blood, urine, cerebrospinal fluid, articular fluid or stool infections, pneumonia, brucellosis, and rickettsiosis. Overall, 664 children < 18 years of age were enrolled; 407 (62.2%) had fever > 38.0 °C and 247 (37.8%) were non-febrile at admission. There were 425 (64.0%), 125 (18.8%), 48 (7.2%), and 66 (9.9%) patients aged 0-24 months, 2-6, 7-12, and > 12 years, respectively. No differences were recorded in the distribution of febrile vs. non-febrile patients among the age groups nor among the 3 neutropenia severity groups (< 0.5, 0.5-1.0 and 1.0-1.5 × 109/L). SBI infections were diagnosed in 98 (14.8%) patients, with higher rates among febrile patients vs. non-febrile patients (16.8% vs. 11.5%, P = 0.06). Brucellosis and rickettsiosis were diagnosed in 15.4% and 23.1% tests performed, respectively. 295/688 (42.9%) virologic examinations returned positive. Among patients < 24 months, more febrile ones had viral infectious compared with afebrile patients (P = 0.025). Acute leukemia was diagnosed in 6 patients. Neutropenia resolved in 163/323 (50.5%) patients during a 1-month follow-up. No differences were recorded in neutropenia resolution between febrile and non-febrile children among all 3 severity groups. Severe neutropenia was rare and occurred mainly in very young patients. SBIs were more common among febrile patients compared with non-febrile patients, but there was no association between severity of neutropenia or its resolution and the presence or absence of fever at diagnosis.

Positive Outcomes of Denosumab Treatment in 2 Patients With Cherubism.

Cherubism is a rare autosomal dominant disease whose severity ranges widely, from asymptomatic to life-threatening. Bilateral symmetrical painless expansion of the mandible and maxilla resulting in a typical appearance of the face resembling a cherub, are the highlighted features of the condition. In most cases, cherubism-induced lesions in the jaws appear around the age of 3 years and tend to expand and increase in numbers until puberty. Treatment options for cherubism range from observation to surgical correction and various pharmacologic therapies. Given the excess sensitivity of cherubism osteoclasts to RANKL (receptor activator of nuclear factor κB ligand) and the positive effects of denosumab (XGEVA; Amgen, Thousand Oaks, CA) treatment in patients with giant cell granuloma, we have designed a treatment based on denosumab for 2 cherubism patients that achieves what we consider promising results.

Treatment of transfusion-dependent congenital dyserythropoietic anemia Type I patients with pegylated interferon alpha-2a.

OBJECTIVE: Pegylated IFN-α2a has been reported in two case reports as being efficacious in treating CDA-I patients. This study aims to assess its efficacy on a series of CDA-I patients. METHODS: Study sample consisted of seven CDA type 1 transfusion-dependent patients. They received pegylated interferon alpha-2a at an initial dose of 90-180 µg once a week, tapered according to clinical response and side effects. Good response was defined as Hb ≥ 10 g/dL for ≥3 months, partial response was defined as 7 ≤ Hb<10 g/dL for ≥3 months, and no response was defined as HB < 7 g/dL for over 3 months on treatment. Time to response was defined as the time needed to achieve hemoglobin levels ≥ 10 g/dL without transfusion. Patients were evaluated periodically by abdominal ultrasounds to rule out liver adenomas. RESULTS: Five patients (71%) had a good response to treatment. One patient stopped treatment due to side effects. One patient had partial response. One patient, with more severe phenotype and poor compliance, had poor response to treatment. No abnormal findings were found in ultrasound examination. No effect on serum ferritin level could be established. CONCLUSION: Pegylated interferon α2a therapy is efficacious in CDA-I patients with a reasonable safety profile.

Septic arthritis in children: Updated epidemiologic, microbiologic, clinical and therapeutic correlations.

BACKGROUND: Septic arthritis (SA) is an infection characterized by significant epidemiologic and microbiologic differences between developed and developing regions and between age groups. OBJECTIVES: To determine the epidemiologic, clinical, microbiologic and therapeutic aspects of pediatric SA in Southern Israel. METHODS: A retrospective case-series study based on the records of children <16 years of age admitted with SA at Soroka Medical Center, Beer-Sheva, during 2006-2013. RESULTS: 189 patients were enrolled. There were 119 (63%) Bedouin and 70 (37%) Jewish children. The knee (39.7%), hip (28%) and ankle (13.8%) were the most commonly involved joints. Blood and/or synovial fluid cultures were positive in 48 (25.4%) patients. Overall SA incidence among children <16 years and <5 years was 11.7 and 25.4/100,000, respectively, without changes throughout the study period. SA incidence among Bedouin children was higher than among Jewish children (15.4 vs. 8.3/100,000 cases). Staphylococcus aureus was the most commonly isolated pathogen (18, 19.5% of all patients), followed by Kingella kingae (10, 5.3%)-(37.5% and 20.8% among culture-positive patients, respectively). The number of children with culture-positive SA that required surgery was higher than those with culture-positive SA treated conservatively (P < 0.001). Hospitalization was longer in children treated surgically than in those treated conservatively (P < 0.001). CONCLUSION: This study is the largest single-center series on pediatric SA published in the last five years and provided an updated picture on incidence and the microbiologic, clinical and therapeutic aspects of pediatric SA in Southern Israel. The study supports a regional presentation pattern of SA and may guide its therapeutic management.

Mucormycosis in children with haematological malignancies is a salvageable disease: a report from the Israeli Study Group of Childhood Leukemia.

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2·2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004-2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3·75; 95% CI 1·51-9·37; P = 0·004) and with increasing age (OR 3·58; 95% CI 1·24-9·77; P = 0·01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9·43; 95% CI 1·47-60·66; P = 0·02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6·42; 95% CI, 1·01-40·94; P = 0·05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 ± 8% and five-year overall survival was 70 ± 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable.

Central venous catheter-associated bloodstream infections in children diagnosed with intestinal failure in Southern Israel.

OBJECTIVES: To study the clinical, epidemiological, and microbiological associations between intestinal failure (IF) and central line-associated infections (CLABSI) in patients with central vein catheters (CVCs) during 2005-2016. METHODS: We compared retrospectively CLABSI rates according to background disease, type of line access, pathogen distribution, and antibiotic susceptibilities. RESULTS: One hundred and fourteen children (64.1% < 4 years) were enrolled. Main diagnoses were persistent diarrhea (20, 17.5%), short bowel syndrome (13, 11.4%), continuous-TPN w/o diarrhea (11, 9.7%), very early-onset inflammatory bowel disease (VEO-IBD, 8, 7%), Hirschsprung's disease (3, 2.6%), non-oncologic hematologic conditions (13, 11.4%), and other diseases (46, 40.4%). 152.749 catheter days were recorded; 71.1% had Hickman's catheters. Two hundred and nine CLABSI episodes were recorded in 58 patients (82% with IF, 13.7 and 8.2/1000 catheter days in IF, and non-gastrointestinal conditions, P = 0.09). More CLABSI were recorded in continuous TPN vs. VEO-IBD or persistent diarrhea (38.8 vs.15.8 and 12.8/1000 catheter days, P < 0.004). Among patients with Hickman in jugular vein, highest CLBSI incidence was in continuous TPN, VEO-IBD, and persistent diarrhea (29.9, 15.84, and 12.49 episodes/1000 catheter days, respectively). CVCs were removed in 38.8% CLABSI. Two hundred and thirty-five pathogens were isolated (Enterobacteriaceae spp. in 39% of IF patients, mostly in persistent diarrhea and short bowel syndrome patients, 47.6% and 34.8%, respectively). Coagulase-negative Staphylococcus was the commonest pathogen in continuous TPN, VEO-IBD, and Hirschsprung's (71.4%, 55.6% and 46.1%, respectively). CONCLUSIONS: CLABSI rates in IF patients were among the highest reported. We reported a "hierarchy" in CLABSI incidence among patients with IF and showed that CLABSI incidence and etiology were different as function of background diseases and CVC insertion site.

Purpuric rash and fever among hospitalized children aged 0-18 years: Comparison between clinical, laboratory, therapeutic and outcome features of patients with bacterial versus viral etiology.

BACKGROUND: The evaluation of children with purpuric rash and fever (PRF) is controversial. Although many of them have viral infections, on occasion such patients may be infected with Neisseria meningitidis. We described all children aged 0-18 years with PRF in southern Israel during the period 2005 ̶ 2016 and compared their microbiologic, laboratory, clinical and outcome characteristics in relation to various etiologies of this syndrome. METHODS: Data were summarized from electronic patient and microbiology files. Viral diagnoses were made by serology and/or PCR. RESULTS: Sixty-nine children with PRF were admitted; 30 (43.48%), 9 (13.04%) and 30 (43.48%) had a syndrome of bacterial, viral or non-established etiology, respectively. N. meningitidis infection was diagnosed in 16/69 (23.19%) patients and in 16/30 (53.33%) patients with bacterial etiology; 14/30 (46.67%) patients suffered from a non-invasive bacterial disease (9 with Rickettsial disease). Adenovirus and Influenza B (3 and 2 cases, respectively) represented the most frequent etiologic agents among patients with viral etiology. More patients with PRF of bacterial etiology were older, of Bedouin ethnicity, looked ill on admission, had higher rates of meningitis and were treated more frequently with antibiotics compared with patients with non-bacterial PRF. Fatality rates among patients with bacterial, viral and non-established etiology were 5/30 (16.7%), 0% and 2/39 (5.1%). CONCLUSIONS: Although PFR was uncommon, high rates of meningococcal infections were recorded in children with PRF, which was associated with high fatality rates. Rickettsial infections were frequent, emphasizing the need for a high index of suspicion for this disease in endemic geographic areas.

The Infectious and Noninfectious Etiology, Clinical Picture and Outcome of Neutropenia in Immunocompetent Hospitalized Children.

BACKGROUND: Acquired neutropenia in immunocompetent children is common, and its differential diagnosis ranges from benign causes to life-threatening diseases. We described the etiology, clinical picture and outcome of new-onset neutropenia in immunocompetent children assessed in the emergency department and hospitalized at our medical center. METHODS: Previously healthy children admitted with neutropenia (absolute neutrophil count <1.5 × 10(9)/L) were included. Serious bacterial infections were defined as culture-positive blood, urine, cerebrospinal fluid, articular fluid or stool infections, pneumonia, Brucellosis and Rickettsiosis. RESULTS: A total of 601 patients (5 days-202 months old) were enrolled; 3 (0.5%), 48 (8%), 165 (27.5%) and 385 (64%) had absolute neutrophil counts <0.2, 0.2-0.5, 0.5-1.0 and 1.0-1.5 × 10(9)/L, respectively. Associated leukopenia and thrombocytopenia were diagnosed in 186 (39%) and 71 (11.8%) patients. Three hundred sixteen of 601 (52.6%) and 519 of 601 (86.4%) were <2 or 36 months of age, respectively. Fever at admission was present in 27.6% patients. Serious bacterial infections were diagnosed in 106 (17.6%) patients. Brucellosis and rickettsiosis were diagnosed in 8 of 52 (15.4%) and 9 of 39 (23.1%) tests obtained. Respiratory syncytial virus was diagnosed in 17 of 33 (51.5%) nasal washes. An infectious etiology was determined in 171 (28.5%) patients. Acute leukemia was diagnosed in 6 patients. A significant correlation was found between resolution of neutropenia and patient age, infectious etiology and severity of neutropenia. CONCLUSIONS: (1) Severe neutropenia was rare; (2) More than half of patients were <2 months of age; (3) An infectious etiology was diagnosed in a high number of patients, and serious bacterial infections were frequent and (4) Brucella spp. and rickettsial infections were frequent etiologies associated with neutropenia in our setting.

Current data on acute haematogenous osteomyelitis in children in Southern Israel: epidemiology, microbiology, clinics and therapeutic consequences.

BACKGROUND: Acute haematogenous osteomyelities (AHO) is the most common form of osteomyelitis, occurring when bone is infected secondary to transient bacteremia. The prevalence, aetiology and outcome of AHO may vary from region to region and period to period. The study objectives were to define the epidemiology, clinical, laboratory and imaging characteristics and treatment consequences of AHO in children in southern Israel. METHODS: This was a retrospective cohort study, enrolling all children <16 years of age hospitalized with AHO. Epidemiologic, clinical, laboratory and imaging data were recorded from medical charts. RESULTS: Ninety-one patients were diagnosed with AHO (52.7 % <4 years of age). Most children (80.24 %) did not receive antibiotic treatment prior to diagnosis. During 2005-2012 the AHO incidence was 5.6:100,000; the AHO incidence in the Bedouin and Jewish population was 7.3 and 4.1:100,000, respectively. Fifty-four (57.8 %) patients were afebrile at admission and 34 (37.4 %) showed leukocytosis >15,000/mm(3). The most involved bone was tibia (39.6 %), followed by femur (19.8 %), humerus (8.8 %) and pelvis (8.8 %). Positive cultures were reported in 26 (28.6 %) patients. The most common pathogen was methicillin-susceptible Staphylococcus aureus (MSSA, 18 patients, 19.8 %). There was only one case of MRSA. More positive cultures were recorded among children requiring surgery compared to children treated conservatively (P < 0.01). MSSA representation in cases requiring surgical intervention was higher than in cases treated conservatively (P = 0.01). There were nine bone biopsies and 33 bone aspirations (MSSA in 44.4 % and 24.2 %, respectively). The longest hospitalization was observed in patients with humerus-AHO (14.8 ± 12.2 days). There was no difference in the number of days of hospitalization between patients who received previous antibiotics compared with children who did not receive antibiotics before admission. CONCLUSIONS: Tibia was the most frequently involved bone, but humeral AHO required more surgical intervention and longer hospitalization. Negative cultures were frequent, MSSA was the most commonly involved pathogen and MRSA was rare. Culture positive AHO was associated with higher requirement for surgical intervention.

Spinal Epidural Hematoma Following Cupping Glass Treatment in an Infant With Hemophilia A.

A 6 months old infant, diagnosed with a rare mutation causing severe hemophilia A, presented with spinal epidural hematoma. Parents later admitted the infant had glass cupping therapy performed within 2 weeks of the onset of symptoms. The rare mutation, rare bleeding complication, and the eventual course of therapy applied in this case will be discussed in our case report.

Skin Necrosis and Purpura Fulminans in Children With and Without Thrombophilia--A Tertiary Center's Experience.

Purpura fulminans (PF) is a very rare clinicopathologic skin disorder comprising dermal microvascular thrombosis associated with perivascular hemorrhage of multiple origins. It may occur as the presenting symptom of severe congenital deficiency of protein C (PC) or protein S (PS) during the newborn period, or later in life following oral anticoagulant therapy with vitamin K antagonists, or of sepsis that may be associated with disseminated intravascular coagulation. Treatment consists of anticoagulants and PC concentrates during acute episodes. We report our experience in the diagnosis and management of pediatric PF. The medical records of the 6 children aged 2-16 years (median: 5 years) who presented with PF to our tertiary care center between 1996 and 2013 were studied. The thrombophilia workup revealed either the presence of congenital homozygous PC deficiency, prothrombotic polymorphisms (factor V Leiden and FIIG20210A heterozygosity), acquired PC/PS deficiency, or no discernible thrombophilia. The skin necrosis resolved following conservative fresh-frozen plasma/anticoagulant therapy in 2 cases, whereas 3 children required interventional plastic surgery. The sixth case, a 10-year-old child with severe PC deficiency, heterozygous factor V Leiden, and FIIG20210A, received recombinant activated PC. PF in childhood is rare and has multiple etiologies. Understanding of the variable pathogenesis and risk factors will facilitate diagnosis and appropriate clinical management.

Clinical and laboratory parameter dynamics as markers of blood stream infections in pediatric oncology patients with fever and neutropenia.

BACKGROUND: Identifying markers associated with blood stream infection (BSI) in children with fever and neutropenia (FN) could lead to a substantial reduction in unnecessary treatment. STUDY OBJECTIVE: The aim of this study was to determine the association between clinical/laboratory parameters and BSI in pediatric oncology patients with FN. METHODS: This prospective study was conducted between 2007 and 2010 at the Pediatric oncology unit. Clinical and laboratory parameters were obtained from all hospitalized FN patients. Linear regression and trends were calculated to determine the association between clinical/laboratory parameters and BSI. RESULTS: Of the 195 FN episodes in 73 children, BSIs were identified in 38 (19%) episodes. Gram-positive bacteria, gram-negative bacteria, and fungi caused 47%, 43%, and 10% of all BSIs, respectively. Mean fever duration was longer in the BSI group (5 d) compared with the non-BSI group (2 d, P=0.01). Mean (±SD) monocyte count at admission was lower in the BSI group compared with the non-BSI group (0.06±0.1 vs. 0.14±0.33 cells/mm, respectively, P=0.05). Mean C-reactive protein (CRP) levels at hospitalization days 5 to 8 were higher in children with BSI (P<0.001). Increment trends of monocyte and platelet levels and decrement trend of CRP levels were noted in the BSI group but not in the non-BSI group (P<0.01 for all). CONCLUSIONS: Prolonged fever, lower monocyte count at admission, higher CRP levels between the fifth and the eighth hospitalization days, increment trends of monocyte and platelet levels, and CRP level decrement were associated with BSI. These factors may serve as markers for BSI in pediatric oncology patients with FN.

Influenza A/H1N1 in pediatric oncology patients.

BACKGROUND: Our aim was to determine the clinical and epidemiological features of pandemic influenza A/H1N1 in immunocompromised children with solid tumors and hematological malignancies. PATIENTS AND METHODS: A prospective study was conducted during the H1N1 pandemic between August 2009 and February 2010 in a pediatric hematology-oncology unit. Demographic and clinical data were obtained from all children with suspected H1N1 infection (high fever with or without respiratory symptoms). Laboratory diagnosis of influenza A/H1N1 was performed by means of polymerase chain reaction analysis of nasopharyngeal wash specimens. RESULTS: We identified 57 episodes of suspected influenza A/H1N1 infection in 40 children. In all episodes, children were treated with oseltamivir and antibiotics until influenza A/H1N1 results were received. Of all episodes, 13 (22.8%) tested positive for influenza A/H1N1. Two of the H1N1-positive children (15.4%) had been previously immunized against influenza A/H1N1. No differences between H1N1-positive and H1N1-negative children were noted in terms of demographic features, clinical presentation, laboratory findings, and underlying disease.Three polymerase chain reaction-positive (23.0%) children and 1 H1N1-negative (2.3%) child were admitted to the pediatric intensive care unit and were mechanically ventilated (P=0.03). One (7.7%) H1N1-positive patient died versus none of the H1N1-negative patients (P=0.2). The condition of all other children in both the groups improved rapidly during hospitalization. CONCLUSIONS: Febrile hospitalized pediatric oncology patients, with and without pandemic influenza A/H1N1, had a similar demographic and clinical presentation with a relatively good outcome. This was probably because of early antiviral treatment and possibly because of the relatively low virulence of the virus. Immunization should be encouraged in these patients.

Surfactant impairs coagulation in-vitro: a risk factor for pulmonary hemorrhage?

BACKGROUND: Pulmonary hemorrhage (PHEM) complicates the hospital course of 3-5% of preterm infants with respiratory distress syndrome (RDS), and bears a high mortality rate. Impaired thrombin generation and poor clot formation in premature neonates affect PHEM severity. OBJECTIVES: We evaluated the impact of surfactant upon in-vitro clot formation in order to assess the role of surfactant in the pathogenesis of PHEM. METHODS: Blood samples were obtained from healthy volunteers for measuring complete blood count, PT, PTT, and platelet function. Surfactant at increasing concentrations was added to blood samples, and whole blood clotting assays were performed using rotation thromboelastogram (ROTEM®, Pentapharm Munich, Germany) and whole blood platelet adhesion and aggregation (Impact-R®, Diamed, Switzerland). RESULTS: The mean PT level increased from 10.05 ± 033 to 11.64 ± 0.85 sec (p=0.06) in the presence of surfactant. Platelet aggregation with the agonists adenosine diphosphate and epinephrine significantly decreased with escalating surfactant concentration (p<0.001). Adhesion, manifested by surface coverage (SC), significantly decreased with increasing surfactant concentration: mean SC 9.25 ± 2.96 compared to 6.1 ± 0.96 and 0.05 ± 0.058 with 0/0.1/5mg/ml surfactant, respectively, p<0.001 Whole blood ROTEM studies showed a trend towards lengthening of clotting time with increased surfactant concentration and lower clot strength. CONCLUSION: The presence of surfactant impairs coagulation in-vitro. The risk of PHEM may therefore be greater in extremely premature infants. Future studies are required to assess the clinical significance and relevance of our preliminary findings.

[Microbiological characteristics of pathogens causing bacteremia among hospitalized pediatric oncology patients with fever and neutropenia].

BACKGROUND: Bacterial infections are a major threat to pediatric oncology patients with fever and neutropenia. Current management consists of empiric broad-spectrum antibiotics and prompt medical evaluation. Local bacterial susceptibility rates were published in 2005, and the local protocol (piperacillin and amikacin) was established as an adequate empiric treatment with -100% efficiency against the common pathogens in our pediatric hemato-oncology ward. AIM: To characterize the spectrum of bacteria isolated from blood cultures at the pediatric hemato-oncology ward between 2008- 2010, and to evaluate the current protocol. METHODS: A prospective study, conducted in the pediatric hemato-oncologic ward among hospitalized children (2 months - 18 years) with fever and neutropenia. Blood cultures from peripheral blood and central lines were obtained from all patients at admission. Bacterial resistance to various antimicrobial agents was determined. RESULTS: During 2008-2010, 195 admissions (105 children) due to fever and neutropenia were recorded. Approximately 30% of all blood cultures were positive for a pathogen with -50% Gram positive bacteria mostly CONS. The most prevalent Gram negative bacteria were acinetobacter and klebsiella spp. Candida species were isolated from 7% of positive cultures. Susceptibility rates for the current empiric antimicrobial regimen were about 90%. CONS bacteremia rate increased from 4% in 2000-2002 to 29% in 2008-2010 (p < 0.01). CONCLUSIONS: The currently applied empiric antimicrobial protocol is an optimal first line regimen, considering the susceptibility of the most common pathogens. Judicious use of carbapenems for gram negative bacteria and glycopeptides or other novel antimicrobial agents in cases of CONS bacteremia is required.