Incidence, Predictors, and Outcomes of Pseudomonas aeruginosa Associated Acute Appendicitis in Children.

BACKGROUND: Pseudomonas aeruginosa (PSA) is an infectious pathogen associated with acute appendicitis; however, it is not consistently addressed by empirical antibiotic therapy, despite potential complications. OBJECTIVES: To investigate the incidence, predictors, and outcomes of PSA-associated acute appendicitis in children. METHODS: We conducted a retrospective analysis involving pediatric patients who underwent acute appendicitis surgery and had positive peritoneal cultures. Clinical, microbiological, and intraoperative data were extracted from medical records. RESULTS: Among 2523 children with acute appendicitis, 798 (31.6%) underwent peritoneal cultures, revealing 338 positive cases (42.3%), with PSA detected in 77 cases (22.8%). Children with PSA were three times more likely to exhibit high intraoperative grading ≥ 3 (93.4% vs. 76.8%, 95% confidence interval [95%CI] 1.2-8.3, P = 0.023) and nearly four times more likely to have polymicrobial cultures (88.3% vs. 62.1%, 95%CI 1.8-8.0, P < 0.001) than those without PSA in peritoneal cultures. Duration of symptoms did not predict PSA isolation (P = 0.827). Patients with PSA had longer median hospital stays (8 days, interquartile range [IQR] 7-10) than those with other pathogens (7 days, IQR 5-9) (P = 0.004). Antibiotic treatment duration, intensive care unit admission rates, readmission, and mortality were similar between the two groups (P = 0.893, 0.197, 0.760, and 0.761, respectively). CONCLUSIONS: PSA is a common pathogen in children diagnosed with acute appendicitis and positive peritoneal cultures. The likelihood of isolating PSA increases with high-grade intraoperative assessment and in the presence of multiple pathogens in peritoneal cultures, suggests antipseudomonal treatment.

The intraperitoneal bacteriology and antimicrobial resistance in acute appendicitis among children: a retrospective cohort study between the years 2007-2017.

This study aims to describe the microbiology and susceptibility profile of the intraperitoneal flora in complicated appendicitis. It is a retrospective cohort study including children < 18-year-old with pathologically confirmed appendicitis, from 2007 to 2017. It included 1466 children. Intraperitoneal samples were obtained from 655 (44.7%) patients, and 201 (30.7%) had positive culture with 395 pathogens. Gram-negative rods comprised 67.6%, Gram-positive cocci 21.5%, and anaerobes 10.9% of the isolates. Gram-positive cocci were detected in 67 (37.8%) patients. Milleri group Streptococci was the most frequently isolated Gram-positive (44.7%). The proportional rate of Milleri group Streptococci from Gram-positive cocci increased from 9.5 to 56.3% (P < 0.001, OR 12.214). Patients with Gram-positive cocci had longer hospital stay (mean 9.36 + 6.385 vs 7.72 + 4.582, P = 0.036, (CI -3.165, -0.105)) and more complicated disease (89.5% vs 78.4%, P = 0.045, OR 2.342). Patients with Milleri group Streptococci isolates readmitted more frequently (26.5% vs 13.2%, P = 0.05, OR 2.37). Resistance to amoxicillin-clavulanate, gentamicin, ceftazidime, piperacillin-tazobactam, and amikacin were detected in 29.1%, 6.5%, 2.3%, 1.2%, and 0.7% of the Gram-negative rods, respectively.Conclusion: The rates of Gram-positive cocci and particularly Milleri group Streptococci in peritoneal fluid are increasing. More complicated disease and longer hospital stay in Gram-positive cocci and higher readmission rate in Milleri group Streptococci. These emphasize the role of anti-Gram-positive antimicrobials. What is known: • Gram-negative rods are the main isolates in complicated appendicitis. • The choice of antibiotic regimen is an unsettled issue due to resistance. What is new: • Increased rate of Gram-positive cocci and Milleri group Streptococci. • More complicated disease, longer hospital stay, and higher readmission rate.

Eculizumab Is Safe and Effective as a Long-term Treatment for Protein-losing Enteropathy Due to CD55 Deficiency.

OBJECTIVES: Loss of the complement inhibitor CD55 leads to a syndrome of early-onset protein-losing enteropathy (PLE), associated with intestinal lymphangiectasia and susceptibility to large-vein thrombosis. The in vitro and short-term treatment benefits of eculizumab (C5-inhibitor) therapy for CD55-deficiency have been previously demonstrated. Here we present the 18-months treatment outcomes for 3 CD55-deficiency patients with sustained therapeutic response. METHODS: Three CD55-deficiency patients received off-label eculizumab treatment. Clinical and laboratory treatment outcomes included frequency and consistency of bowl movements, weight, patient/parent reports of overall well-being, and serum albumin and total protein levels. Membrane attack complex deposition on leukocytes was tested by flow cytometry, before and during eculizumab treatment. RESULTS: Marked clinical improvement was noted in all 3 patients with resolution of PLE manifestations, that is, diarrhea, edema, malabsorption, overall well-being, growth, and quality of life. In correlation with the clinical observations, we observed progress in all laboratory outcome parameters, including increase in albumin and total protein levels, and up to 80% reduction in membrane attack complex deposition on leukocytes (P < 0.001). The progress persisted over 18 months of treatment without any severe adverse events. CONCLUSIONS: CD55-deficiency patients present with early-onset diarrhea, edema, severe hypoalbuminemia, abdominal pain, and malnutrition. Targeted therapy with the terminal complement inhibitor eculizumab has positive clinical and laboratory outcomes in PLE related to CD55 loss-of-function mutations, previously a life-threatening condition. Our results demonstrate the potential of genetic diagnosis to guide tailored treatment, and underscore the significant role of the complement system in the intestine.

Emergency or urgent splenectomy in children for non-traumatic reasons.

Emergency splenectomy is rarely performed since a widespread consensus exists towards conservative management of splenic injury. However, in selected conditions, mainly hematological, there is a role for emergency or urgent splenectomy. This study aims to retrospectively review these cases and discuss outcome in relation to the pre-existing splenic pathologies. Between 2000 and 2015, 12 patients, five girls, and seven boys, with a median age of six years (3 months-13.11 years), underwent emergency or urgent splenectomy for non-traumatic conditions. All patients had major associated disorders; mainly hematological (11 cases) including hemolytic anemia with pancytopenia (1), sickle cell anemia (1), AML (1), ALL (2), CML (1), T cell lymphoma (1), Burkitt lymphoma (1), and ITP (3). One patient had a microvillous inclusion disease. Indications for splenectomy included diffuse resistant splenic abscesses (4), intracranial hemorrhage (4) or hypersplenism (3) with refractory thrombocytopenia, and spontaneous splenic rapture (1). Nine patients improved following surgery but three died, owing to massive intracranial hemorrhage (1) and severe respiratory failure (2) despite aggressive management.Conclusions: Rarely, an emergency splenectomy is required in complex settings, mostly refractory hematological conditions, in a deteriorating patient when all other measurements have failed. A multidisciplinary team approach is mandatory in the treatment of these complex cases. What is known • Conservative treatment is advised for splenic injury. • Many hematological disorders are responsible of splenic pathology. What is new • Emergency splenectomy in children for reasons other than trauma is a treatment of last resort that should be performed in a multidisciplinary context. • The outcome of emergency splenectomy in children for reasons other than trauma depends on the underlying medical condition.

Hypogammaglobulinemia in the early period after liver transplantation in children.

Data, on the kinetic and serum levels of immunoglobulins in the immediate post-liver transplantation (LTx) period, are sparse with existing studies limited to adults or case reports of children. The aim of this study is to describe the phenomenon of hypogammaglobulinemia (HGG) in the immediate post-transplantation period among children undergoing LTx. A retrospective 10-yr chart review was conducted of all children who underwent LTx at a fourth-level pediatric medical center. Fifty-seven, of the 76 children who underwent LTx, were included in the study. Seventeen (29.8%) (mean age, 6.8 ± 5.2 yr) had HGG (11-IgG, 1-IgG+IgA, 1-IgG+IgM, 4-IgG+IgA+IgM), detected at 2 to 25 d after transplantation. Abdominal fluid was drained for 5 to 42 d; the amount drained until detection of HGG measured 27-668 mL/kg. HGG was associated with increased infection rate 0.9 episodes/patient vs. 0.17 episodes/patient (p < 0.01) in children without detected HGG. In conclusion, HGG is not rare in the immediate post-LTx period in children, and it may place patients at increased risk of infection. Further studies are needed to delineate the rate of occurrence, risk factors, and clinical implications of hypogammaglobulinemia in this patient population.

Simultaneous Renal Transplantation With Bilateral Nephrectomy and Ureterocystoplasty.

Bladder augmentation (BA) may be required before renal transplantation in children with end stage renal disease (ESRD). Herein we report a case of a 7-year-old boy with ESRD, contracted bladder and severe bilateral reflux secondary to posterior urethral valve (PUV), successfully managed by simultaneous bilateral nephrectomy, bilateral ureterocystoplasty and renal transplantation.

2p24 Gain region harboring MYCN gene compared with MYCN amplified and nonamplified neuroblastoma: biological and clinical characteristics.

Although the role of MYCN amplification in neuroblastoma is well established, the biological and clinical characteristics of the 2p gain region harboring the MYCN gene remain unclear. The aim of this study was to compare the biological and clinical characteristics of these tumors with MYCN amplified and nonamplified neuroblastoma and to determine their impact on disease outcome. Samples from 177 patients were analyzed by fluorescence in situ hybridization, including MYCN, 1p, 17q, and 11q regions; 2p gain was identified in 25 patients, MYCN amplification in 31, and no amplification in 121 patients. Patients with 2p gain had a significantly worse 5-year event-free survival rate than patients with no MYCN amplified (P < 0.001), and an intermediate 5-year overall survival rate difference existed between the MYCN amplified tumors (P = 0.025) and nonamplified (P = 0.003) groups. All of the 2p gain samples were associated with segmental and/or numerical alterations in the other tested regions. The presence of segmental alterations with or without MYCN amplification was recently found to be the strongest predictor of relapse in a multivariate analysis. The results of the present study suggest that the determination of MYCN gene copy number relative to chromosome 2, when evaluating MYCN status at diagnosis, may help to reveal the underlying genetic pattern of these tumors and better understand their clinical behavior.

Nitric oxide for post-liver-transplantation hypoxemia in pediatric hepatopulmonary syndrome: case report and review.

HPS is rare in the pediatric population. Liver transplantation is the ultimate treatment for severe HPS. There are only a few case reports and one series of children in whom HPS was the main indication for liver transplantation. Outcome was good in most of them, with full regression of the pulmonary process. However, hypoxemia in the early post-operative course can have severe consequences, and effective treatment modalities are needed. There are rare instances of the use of iNO for the treatment of post-operative hypoxemia. We describe a 10.5-yr-old boy with severe HPS owing to chronic liver disease after bone marrow transplantation. Liver transplantation from a living related donor (the same sister who donated the bone marrow) was complicated by severe hypoxemia on POD 2. iNO was administered via the ventilator circuit and, after extubation, through nasal prongs. It was slowly tapered down and stopped on POD 10. The child had an otherwise uneventful course and was discharged home on POD 21 with normal oxygen saturation. Liver transplantation should be offered to children with severe HPS. iNO can reverse the hypoxemia that may occur after the operation.

Reduced levels of miR-34a in neuroblastoma are not caused by mutations in the TP53 binding site.

Neuroblastoma (NB) is the most common extracranial solid tumor in children below the age of 5 years. miR-34a, located in chromosome band 1p36, has been recently implicated as a tumor suppressor gene in NB. In addition, it has been shown that miR-34a is activated by TP53 by binding to a TP53 binding site upstream to the mature miR-34a. We studied NB tumors from 57 patients for miR-34a expression levels, 1p status, mutations in the TP53 coding region and mutations of the TP53 binding site. Reduced expression levels of miR-34a were identified in tumors harboring 1p36.3 Loss (P = 0.028). No mutations were identified in the coding region of TP53, or in the TP53 binding site. Thus, mutations in the binding site are not an additional mechanism for the inactivation of miR-34a in NB. Other regulatory mechanisms controlling miR-34a expression and its relationship to TP53 should be further explored.

Living-related donor liver transplantation for children with fulminant hepatic failure in Israel.

BACKGROUND: Liver transplantation is considered the treatment of choice for most children with deteriorating fulminant hepatic failure (FHF). Living-related donor liver transplantation (LDLT) has been suggested as an alternative to cadaveric liver transplantation to overcome the shortage of organ donors. However, experience with LDLT for children with FHF is limited in the Western world. OBJECTIVE: To present the experience with LDLT for children with FHF in a major referral center in Israel. METHODS: The files of all children who underwent primary LDLT for FHF were reviewed for demographic, clinical, and laboratory parameters before and after transplantation. RESULTS: : During 1996 to 2007, 13 children diagnosed with FHF underwent primary LDLT. Median age was 4 years (range 0.75-14 years); the causes of FHF were acute hepatitis A in 4 patients and were unknown in 9 patients. Short-term complications, documented in 12 children, included mainly hepatic artery thrombosis (n = 5), which warranted retransplantation in 3 cases, and biliary leaks (n = 3). Three patients died within the first month after LDLT of severe intraoperative bleeding (n = 1), severe brain edema (n = 1), and multiorgan failure (n = 1). Long-term complications were less common and included mainly ascending cholangitis (n = 3). Patient survival rate was 68% at 1 year and 57% at 5 years. None of the donors had long-term complications. CONCLUSIONS: Among children with FHF, LDLT can serve as a timely and lifesaving alternative to cadaveric donation, and could reduce the dependence on cadaveric livers in this setting.

Conservative approach to the treatment of injured liver and spleen in children: association with reduced mortality.

BACKGROUND: Previous analyses of the safety of the conservative versus the operative approach to the treatment of liver and spleen blunt injuries in children often failed to account for differences in quality of care and expertise among dedicated pediatric trauma center, non-pediatric centers, centers without trauma units, and non-trauma centers. To eliminate this potential bias, the present study examined changes in the rate of surgery and their impact on outcome within the same medical centers over time. METHODS: The Israel Trauma Registry was searched for patients <18 years who were treated for non-penetrating liver or spleen injuries from 1998 to 2004. Patients were grouped by period, 1998-2000 and 2001-2004, and compared for type of injury, severity of injury, type of treatment, and inpatient mortality. RESULTS: The earlier period (1998-2000) was characterized by a significantly higher rate of operations compared with the later period (2001-2004) (P = 0.001) and higher in-hospital mortality (P = 0.04). Injury severity scores, type of organs injured, and accompanying injuries were similarly distributed in the two groups. CONCLUSIONS: Despite the similarity in the severity and characteristics of the intraabdominal injuries in 1998-2000 and in 2001-2004, the proportion of children treated conservatively increased over time, concomitant with a significant drop in inpatient mortality. We attribute this shift over a relatively short interval to increased experience and greater acceptance of conservative management in this setting.

ImmuKnow: a new parameter in immune monitoring of pediatric liver transplantation recipients.

Lifelong immunosuppression is mandatory for optimal graft and patient survival following liver transplantation. Nevertheless, graft rejection or numerous adverse events associated with overimmunosuppression or underimmunosuppression cannot be completely avoided. The ImmuKnow assay measures cell-mediated immunity and is able to discern between conditions of overimmunosuppression and underimmunosuppression. The aim of this study was to evaluate the ImmuKnow assay in the evaluation of the immune function in pediatric liver transplant recipients and to assess its correlation with the patients' clinical and biochemical status. Eighty-nine whole blood samples were collected from 23 liver transplant recipients that were 1 to 18 years old. The net state of immune function was determined by the quantitative measurement of the intracellular adenosine 5-triphosphate level in CD4+ lymphocytes after phytohemagglutinin stimulation. Comprehensive clinical data were correlated with the ImmuKnow assay results. In 23 of the 28 samples collected during clinical quiescence, ImmuKnow results were correlated with the clinical status, expressing the patient's moderate immune function. However, a correlation between measured therapeutic drug levels and clinical quiescence was found in only 18 of the 28 samples. In 6 patients who suffered from clinical complications, ImmuKnow measurements showed a wide range of deviations, expressing the unstable immunological status of these patients. In conclusion, the ImmuKnow assay correlates with the clinical status of liver-transplanted children. It serves as a reliable and unique parameter of the cellular immune function. We conclude that the ImmuKnow assay, together with existing clinical tools, may allow for the immune monitoring of pediatric liver recipients.

Colorectal carcinoma in childhood: a retrospective multicenter study.

OBJECTIVES: Colorectal carcinoma, a common adult malignancy, has an estimated childhood incidence of 0.3 to 1.5/million in Western countries and 0.2/million in Israel. Diagnosis is difficult because adult screening measures are unfeasible in children. The tumor is frequently associated with predisposing genetic factors, aggressive biological behavior, and poor prognosis. The aim of this multicenter study was to document the clinical profile, treatment and prognosis of colorectal carcinoma in children in Israel. PATIENTS AND METHODS: The clinical, laboratory, therapeutic, and prognostic parameters of all 7 children from 4 medical centers in Israel who were diagnosed with colorectal carcinoma over a 25-y period were reviewed. RESULTS: Patients presented with rectal bleeding (4 of 7), abdominal pain (2 of 7), and abdominal distension (2 of 7). Average time to diagnosis was 6 months. Six patients underwent surgery (1 refused), and 5 received chemotherapy. Histopathological studies showed poorly differentiated mucinous adenocarcinoma, signet-ring type, in 4 cases, moderately differentiated adenocarcinoma in 2, and well-differentiated carcinoma in 1. Three patients died of the disease, 2 shortly after diagnosis. One patient with recurrent metastatic disease was lost to follow-up. CONCLUSION: Colorectal carcinoma in children is characterized by aggressive tumor behavior and delayed diagnosis, resulting in a worse prognosis than in adults. Heightened physician awareness of the possibility of this disease in children, with special attention to adolescents with predisposing factors and rectal bleeding, could help to improve outcome.

Kingella Kingae Chest Mass Mimicking a Tumor in an 11-Month-Old Baby.

Kingella kingae has been recognized as a common etiology of pediatric osteoarticular infections, especially among children younger than 5 years of age. In recent years, there have been reported cases of unusual manifestations. We report a rare case of a chest mass mimicking a tumor in an 11-month-old baby.

Life-threatening airway obstruction secondary to mass in children-a preventable event?

OBJECTIVES: To investigate the management of children with life-threatening airway obstruction from large mediastinal masses. METHODS: Review of the medical records of children with mediastinal masses and severe airway obstruction who were admitted to a multidisciplinary pediatric intensive care unit. RESULTS: Eight patients with 12 life-threatening events were identified. Five events (in 4 patients) occurred before hospital admission, and 3 patients had more than 1 choking episode. Five patients underwent cardiorespiratory resuscitation (2 before admission), and 2 underwent emergency endotracheal intubation because of severe airway obstruction; the eighth patient could not be weaned off the ventilator until the mediastinal mass was resected. Median time from appearance of the initial symptoms to diagnosis was 8.5 days, and median time from the onset of alarming signs to admission was 2 days. CONCLUSIONS: Severe airway obstruction in children with an anterior mediastinal mass is not rare and can lead to complete obstruction, requiring cardiorespiratory resuscitation. Physician awareness and preparedness for respiratory complications are essential for proper management of children with mediastinal masses.

Two year experience with minimal access surgery at Schneider Children's Medical Center of Israel.

BACKGROUND: The minimal access surgery revolution has only just begun to impact on pediatric surgery, thanks mainly to technologic advances and evidence of the benefits of minimally invasive procedures in this population. OBJECTIVES: To review the current status of MAS in a pediatric tertiary care center in Israel, in terms of feasibility, safety, and effect on standard practices. METHODS: We reviewed the files of all children who underwent a MAS procedure in our department during the period April 2002 to July 2004, and compared the findings with those of children treated by standard practices. RESULTS: A total of 301 procedures were performed in 271 patients: 107 thoracoscopic and 194 laparoscopic. There were no major intraoperative complications. The total conversion rate was 3.65%: 0 for thoracoscopy and 5.6% for laparoscopy (11/194). Twenty-four types of procedures were performed during the study period. The thoracoscopies accounted for 92.24% of all thoracic procedures in the department (107/116), and routine abdominal laparoscopic procedures replaced open surgery in 30-100% of cases (total 44.8%, 194/433). CONCLUSIONS: MAS procedures appear to be safe for a wide range of indications in children. In our center they currently account for a significant percentage of pediatric surgeries. We suggest that the integration of MAS training in the residency programs of pediatric surgeons be made a major long-term goal. The creation of a pediatric MAS study group that would allow for multi-institutional studies is especially important in Israel where a relatively large number of pediatric surgery departments handle a small annual number of patients.

Compliance with surgical antibiotic prophylaxis guidelines in pediatric surgery.

INTRODUCTION: Surgical antibiotic prophylaxis (AP) guidelines balance the need to prevent infection with the risks of adverse drug effects. Our aim was to assess compliance with AP guidelines. METHODS: A retrospective study was performed in a pediatric medical center. Included were patients aged 0 to 18 years that underwent clean-contaminated surgery during a 1-year period (2008-2009) and required AP. Compliance with four AP bundle guidelines was evaluated. Risk factors for noncompliance were identified using univariate and multivariate analyses. RESULTS: AP was given to 239 of 247 (96.8%) of patients. Complete compliance with AP guidelines was achieved in 16 of 247 (6.5%) patients. Compliance with guidelines for appropriate antibiotic, drug dose, correct timing, and treatment duration were found in 97.1, 52.2, 31.9, and 35.9% of patients, respectively. Multivariable analysis showed that inappropriate timing was associated with age ≥ 4 years (p = 0.002), urgent surgery (p = 0.0018), surgical department AP administration (p = 0.0001), and night-time surgery (p = 0.015). Incorrect AP dose was associated with presence of comorbidities (p = 0.006). No risk factor was related to incorrect AP duration. CONCLUSIONS: We have found a low rate of full compliance with AP guidelines. AP should only be given in the operating room. Increased awareness to AP guidelines is needed.