Tommy Schonfeld

Early Emergence of Ganciclovir-Resistant Human Cytomegalovirus Strains in Children with Primary Combined Immunodeficiency

Children with primary combined immunodeficiency (CID) and human cytomegalovirus (HCMV) infection often deteriorate despite antiviral therapy. In this study, the emergence of ganciclovir-resistant strains was examined in 6 children with CID and HCMV infection, using sequence analysis of the HCMV UL97 gene and virus susceptibility assays. Mutations in the proposed ATP binding site associated with ganciclovir resistance were found in 4 of the 6 children. In 1 patient with B severe CID, an unusual multiplicity of mutations was found in the UL97 substrate binding domain between aa 590-606. All mutations were detected within 10 days to 3 weeks from initiation of therapy. The emergence of resistant strains in children with CID appears earlier than in other groups of HCMV-infected patients. These findings may have relevance to the cellular pathways involved in viral DNA repair and mutagenesis, and they indicate the need for early and frequent genotypic monitoring and prompt therapeutic modification in this patient population.

Hemophagocytic lymphohistiocytic syndrome: Unrecognized cause of multiple organ failure.

Objective To describe an often-unrecognized clinical picture of multiple organ failure in hemophagocytic lymphohistiocytic syndrome (HLS). Design Retrospective chart review. Setting A ten-bed pediatric intensive care unit (PICU) in a tertiary children’s university hospital. Patients A total of 11 children (age, 5 months to 13 yrs) who fulfilled the criteria for the diagnosis of familial- or infectious-associated hemophagocytic lymphohistiocytosis and who required intensive care support for organ failure. Intervention None. Main Results During a 10-yr period, 5,439 children were hospitalized in our PICU. A total of 11 children were diagnosed as suffering with HLS. Of these 11 patients, three (27%) had the familial form and eight had the infectious-associated form. After admission to the PICU, seven patients (63%) were diagnosed as suffering with HLS and each had one or more organ failures (patients 3–7, 9, and 10). All presented with fever, hepatomegaly, and splenomegaly; in addition, all had at least two of the following: anemia, neutropenia, or thrombocytopenia. All 11 had lymphohistiocytic accumulation in bone marrow (n = 10), lymph node (n = 2), lung (n = 2), and/or liver (n = 1). Organ failure was noted most often in the respiratory system (n = 7) attributable to severe, acute respiratory distress syndrome and pleural effusion. Of the 11 patients, six had cardiovascular involvement that manifested as shock in three and as capillary leak syndrome in three. Renal failure occurred in four patients. Of these, two required hemodiafiltration and one required peritoneal dialysis. Liver failure occurred in three and central nervous system involvement and coma in three. Most of the patients required massive therapeutic intervention, including assisted ventilation (n = 6), inotropic support (n = 3), and hemofiltration (n = 3). A total of seven patients (63%) died. Conclusions Hemophagocytic lymphohistiocytic syndrome in the pediatric population may have a dramatic clinical picture, with multiple organ failure as a presenting symptom or early in the disease course, mandating intensive support in the PICU.

Blood Transfusion Policy among European Pediatric Intensive Care Physicians

The objective of this study was to define current blood transfusion practices among European pediatric intensive care physicians treating critically ill children. A questionnaire of case scenarios was administered to members of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC). Of the 258 members of the ESPNIC, 134 (51.9%) pediatric intensive care physicians completed the questionnaire. The suggested blood transfusion thresholds for case scenario 1 (post–orthopedic surgery child) ranged from <7.0 g/dl to 11 g/dl. A total of 57.3% suggested 7 g/dl, 33.6% suggested 8 g/dl, and 6.9% suggested 9 g/dl as a hemoglobin threshold for transfusion (mean, 7.54 ± 0.75). For case scenarios 2 to 4, the suggested hemoglobin thresholds were 7 g/dl to 12 g/dl. For case scenario 2 (a child with acute respiratory distress syndrome), 22.4% suggested 8 g/dl, 15.7% suggested 9 g/dl, and 41% suggested 10 g/dl as a hemoglobin threshold for transfusion (mean, 9.40 ± 1.27 g/dl). For case scenario 3 (a post–cardiac surgery infant), 20.1% suggested 7 g/dl, 24.6% suggested 8 g/dl, 21.6% suggested 9 g/dl, and 23.9% suggested 10 g/dl as a hemoglobin threshold for transfusion (mean, 8.72 ± 1.24 g/dl). For case scenario 4 (a child with septic shock), 23.1% suggested 8 g/dl, 16.4% suggested 9 g/dl, and 41% suggested 10 g/dl as a hemoglobin threshold for transfusion (mean, 9.45 ± 1.24 g/dl). The threshold for transfusion was not statistically different ( P > .05) between the physicians according to their subspecialty, years of experience, or country of origin. The suggested volume of transfused blood was 10 to 15 ml/kg in 427 responses (82.6%) and 20 ml/kg in 89 responses (17.2%). Most physicians, 78/128 (60.9%), did not consider the age of the transfused blood an important factor in their decision to transfuse. Of the 106 (79.1%) physicians who detailed their considerations for elevating the thresh- old for transfusion, 82 (77.3%) gave a general nonspecific indication, 47 (44.3%) stated hemodynamic instability and shock, and 40 (37.7%) an ongoing bleeding. The hemoglobin threshold for blood transfusion and transfusion volume varies among European pediatric intensive care physicians, for the same patient.

Computerized Scoring System for the Diagnosis of Foreign Body Aspiration in Children

Objectives: Foreign body aspiration (FBA) is a life-threatening event in children. The gold standard for diagnosis is bronchoscopy, but there is no consensus regarding indications for the procedure. The aim of this study was to formulate a predictive model for assessing the probability of FBA in suspected cases as an aid in the decision to perform diagnostic bronchoscopy. Methods: The files of 150 patients who underwent bronchoscopy for suspected FBA at our center between 1996 and 2004 were reviewed for medical history, physical examination, and radiologic studies. The findings were analyzed by logistic regression. Results: Using the file data, we formulated a predictive model wherein each parameter received a numeric coefficient representing its significance in evaluating suspected FBA. The most significant parameters were age 10 to 24 months, foreign body in the childs mouth and severe respiratory complaints during the choking episode, hypoxemia, dyspnea or stridor following the acute event, unilateral signs on lung auscultation, abnormal tracheal radiogram, unilateral infiltrate or atelectasis, and local hyperinflation or obstructive emphysema on chest radiogram. Conclusions: In our predictive model, every case of suspected FBA can be assigned a score based on the specific parameters present, which is then entered into a probability formula to determine the likelihood of a positive diagnosis. This model may serve as a useful tool for deciding on the use of bronchoscopy in all children with suspected FBA.

Bi-Level Positive Airway Pressure Ventilation in Pediatric Oncology Patients With Acute Respiratory Failure

The aim of the study was to describe our experience with bi-level positive airway pressure (BiPAP) ventilation in oncology children with acute respiratory failure, hospitalized in a single tertiary pediatric tertiary center. This was a retrospective cohort study of all pediatric oncology patients in our center admitted to the intensive care unit with acute hypoxemic or hypercarbic respiratory failure from January 1999 through May 2006, who required mechanical ventilation with BiPAP. Fourteen patients met the inclusion criteria with a total of 16 events of respiratory failure or impending failure: 12 events were hypoxemic, 1 was combined hypercarbic and hypoxemic, and 3 had severe respiratory distress. Shortly after BiPAP ventilation initiation, there was a statistically significant improvement in the respiratory rate (40.4 ± 9.3 to 32.5 ± 10.1, P < .05] and a trend toward improvement in arterial partial pressure of oxygen (PaO 2; 71.3 ± 32.7 to 104.6 ± 45.6, P = .055). The improvement in the respiratory status was sustained for at least 12 hours. In 12 (75%) events there was a need for sedation during ventilation; 12 children needed inotropic support during the BiPAP ventilation. Bi-level positive airway pressure ventilation failed in 3 (21%) children who were switched to conventional ventilation. All of them have died during the following days. One child was recategorized to receive palliative care while on BiPAP ventilator and was not intubated. In 12 of 16 BiPAP interventions (75%; 11 patients), the children survived to pediatric intensive care unit (PICU) discharge without invasive ventilation. No major complications were noted during BiPAP ventilation. Bi-level positive airway pressure ventilation is well tolerated in pediatric oncology patients suffering from acute respiratory failure and may offer noninferior outcomes compared with those previously described for conventional invasive ventilation. It appears to be a feasible initial option in children with malignancy experiencing acute respiratory failure.

Mediastinal Tumors in Children: A Single Institution Experience

Mediastinal masses in children are a heterogeneous group of asymptomatic or potentially life-threatening congenital, infectious, or neoplastic lesions that present complex diagnostic and therapeutic dilemmas. Some patients are asymptomatic; in others, the mass may compress mediastinal structures and cause sudden asphyxia. In these cases, close cooperation is needed among pediatric surgeons, anesthesiologists, intensivists, oncologists, and radiologists. The files of 45 children with mediastinal masses admitted between 1986 and 1999 to the Pediatric Intensive Care Unit (PICU) of Schneider Childrens Medical Center of Israel were reviewed. Twenty-one were admitted for perioperative care, and 21 for emergency care, including 19 with respiratory distress. Five of the emergency care group had asphyxia and 10 needed assisted ventilation. Two children were admitted for evaluation and 1 for leukopheresis. The children admitted on an emergency basis had more clinical findings than the postoperative group: almost 80% had dyspnea and more than 45% had oxygen desaturation; 33% had cough and noisy breathing, and 25%, superior vena cava syndrome or hepatosplenomegaly. Eight patients (17.8%) had benign disease and 37 (82.2%) malignant disease. The patients with a benign mass were significantly younger than the patients with a malignant mass (p<0.005); in 5 cases (12.5%), a congenital anomaly presented as a mediastinal mass. Most of the malignant masses were of hematologic origin (40.5%), followed by neurogenic tumors (27%). Twenty-seven patients underwent surgery, including 6 emergency procedures (3 partial resections, 2 biopsies, 1 lymph node biopsy). There were no intraoperative or postoperative deaths. The present series emphasizes the complex care children with a mediastinal mass require. They should be treated in a tertiary center with a multidisciplinary approach.

Central apnoeas in infants with bronchiolitis admitted to the paediatric intensive care unit

Aim:  To further characterize apnoea(s) complicating bronchiolitis because of respiratory syncytial virus (RSV), to describe the incidence of this complication and identify possible risk factors for apnoea(s) and its development.

Pulmonary inflammatory myofibroblastic tumorinvading the left atrium

Inflammatory myofibroblastic tumor is a rare solid tumor that most often affects children and young adults. Although benign, the tumor may be very aggressive locally. We describe a 9-year-old boy with primary inflammatory myofibroblastic tumor of the left upper lobe involving the left atrium.

Laryngomalacia: a cause for early near miss for SIDS

Six infants had recurrent apnea of infancy episodes (near miss sudden infant death syndrome) during their neonatal period. Physical examination and laboratory investigation were normal. Polygraphic sleep monitoring revealed recurrent obstructive sleep apnea. These infants underwent fiberoptic endoscopy which showed that airway obstruction occurred at the laryngeal orifice as a result of laryngomalacia. It is suggested that laryngomalacia may be a cause for early apnea of infancy.

Differential Leukocyte Count in Acute Gastroenteritis An Aid to Early Diagnosis

The total and differential leukocyte counts of 238 infants with acute gastroenteritis were evaluated as an aid in differentiating between nonbacterial and bacterial infection. In contrast to the total leukocyte count, which was noncontributory, the absolute band count and the ratio between band and total neutrophil count (B/N ratio) were helpful, with the highest values seen in patients with Shigellosis. A B/N ratio greater than 0.10 can help differentiate Shigella, Salmonella, and Campylobacter infections from E. coli and nonbacterial gastroenteritis with a sensitivity of 84.3 per cent and a specificity of 74.5 per cent.