The cause of death in bacterial meningitis.

BACKGROUND: Death from bacterial meningitis is rarely attributed to the actual event causing death. The present study therefore categorized and characterized the cause and time of death due to bacterial meningitis. METHODS: In a cohort of patients > 15 years of age with community acquired bacterial meningitis the medical records were reviewed, and a clinical cause of death categorized into six main categories: 1) CNS complications, 2) Systemic complications, 3) Combination of systemic and CNS complications, 4) Sudden death, 5) Withdrawal of care, or 6) Unknown. RESULTS: We identified 358 patients of which 84 (23%) died in-hospital. Causes of death were ascribed to CNS complications in 43%, Systemic complications in 39%, Combined CNS and systemic complications in 4%, Sudden death in 7% and withdrawal of care in 5%. Brain herniation, circulatory failure, intractable seizures and other brain injury were the most common specific causes of death within 14 days from admission (55%). CONCLUSION: Fatal complications due to the primary infection - meningitis - is most common within 14 days of admission. The diversity of complications causing death in meningitis suggest that determining the clinical cause of death is essential to the evaluation of novel treatment strategies.

Early versus late diagnosis in community-acquired bacterial meningitis: a retrospective cohort study.

OBJECTIVES: To examine clinical characteristics and outcome of patients with late diagnosis of community-acquired bacterial meningitis (CABM). METHODS: We conducted a chart review of all adults with proven CABM in three centres in Denmark from 1998 through to 2014. Patients were categorized as early diagnosis of CABM immediately on admission, or late diagnosis if CABM was not listed in referral or admission records and neither lumbar puncture nor antibiotic therapy for meningitis was considered immediately on admission. We used modified Poisson regression analysis to compute adjusted relative risks with 95% CIs for predictors of late diagnosis and in-hospital mortality. RESULTS: A total of 113/358 (32%) patients were categorized as late diagnosis demonstrating a variety of tentative diagnoses of which 81/113 (72%) were non-infectious. We observed several statistically significant baseline differences (p <0.05) in patients with late versus early diagnosis including age >65 years (56/113, 50% versus 67/245, 27%), neck stiffness (35/97, 36% versus 183/234, 78%), concomitant pneumonia (26/113, 23% versus 26/245, 11%), and meningococcal meningitis (6/113, 5% versus 52/245, 21%). These variables remained statistically significant in multivariate analysis. Moreover, late diagnosis was associated with increased in-hospital mortality (41/113, 36% versus 43/245, 18%; adjusted relative risk 1.7, 95% CI 1.2-2.5). CONCLUSIONS: Late diagnosis of CABM was common and patients were admitted with mostly non-infectious diagnoses. Absence of neck stiffness did not rule out CABM and special attention should be given to patients with pneumonia and the elderly. Late diagnosis was associated with incorrect patient management and increased mortality.

Macular and peripapillary retinal nerve fibre layer thickness in patients with cyanotic congenital heart disease.

PURPOSE: To evaluate macular and retinal nerve fibre layer (RNFL) measurements in patients with cyanotic congenital heart disease (cCHD) using spectral domain optical coherence tomography (OCT). PATIENTS AND METHODS: Thirty patients with cCHD (18 females and 12 males, mean age 10.9 years) and 60 healthy controls (35 females and 25 males, mean age 11.2 years) underwent complete ophthalmologic examination and OCT measurements of macular and peripapillary RNFL thickness. RESULTS: Patients with cCHD had significantly thinner measurements in all macular subfields compared with healthy controls (P<0.001). There was no significant difference in peripapillary RNFL thickness between the two groups, with the exception of the upper quadrant, for which thickness measurements were higher in patients with cCHD (P=0.021). CONCLUSIONS: Patients with cCHD showed a significant decrease in macular thickness and a thickened superior quadrant RNFL thickness when compared with healthy controls. This may represent the damage caused by the effect of hypoxia.

Genome-wide identification of Streptococcus pneumoniae genes essential for bacterial replication during experimental meningitis.

Meningitis is the most serious of invasive infections caused by the Gram-positive bacterium Streptococcus pneumoniae. Vaccines protect only against a limited number of serotypes, and evolving bacterial resistance to antimicrobials impedes treatment. Further insight into the molecular pathogenesis of invasive pneumococcal disease is required in order to enable the development of new or adjunctive treatments and/or pneumococcal vaccines that are efficient across serotypes. We applied genomic array footprinting (GAF) in the search for S. pneumoniae genes that are essential during experimental meningitis. A total of 6,000 independent TIGR4 marinerT7 transposon mutants distributed over four libraries were injected intracisternally into rabbits, and cerebrospinal fluid (CSF) was collected after 3, 9, and 15 h. Microarray analysis of mutant-specific probes from CSF samples and inocula identified 82 and 11 genes mutants of which had become attenuated or enriched, respectively, during infection. The results point to essential roles for capsular polysaccharides, nutrient uptake, and amino acid biosynthesis in bacterial replication during experimental meningitis. The GAF phenotype of a subset of identified targets was followed up by detailed studies of directed mutants in competitive and noncompetitive infection models of experimental rat meningitis. It appeared that adenylosuccinate synthetase, flavodoxin, and LivJ, the substrate binding protein of a branched-chain amino acid ABC transporter, are relevant as targets for future therapy and prevention of pneumococcal meningitis, since their mutants were attenuated in both models of infection as well as in competitive growth in human cerebrospinal fluid in vitro.

Hearing loss and cochlear damage in experimental pneumococcal meningitis, with special reference to the role of neutrophil granulocytes.

Hearing loss is a well-known sequelae from meningitis, affecting up to 25% of survivors. However, the principal components of the infectious and inflammatory reaction responsible for the sensorineural hearing loss remain to be identified. The present study aimed to investigate the impact of an augmented neutrophil response on the development of hearing loss and cochlear damage in a model of experimental pneumococcal meningitis in rats. Hearing loss and cochlear damage were assessed by distortion product oto-acoustic emissions (DPOAE), auditory brainstem response (ABR) and histopathology in rats treated with ceftriaxone 28 h after infection. Rats were treated with Granulocyte Colony Stimulating Factor (G-CSF) initiated prior to infection, 28 h after infection or with ceftriaxone only. Rats were followed for 7 days, and assessment of hearing was performed before infection and 24 h and day 8 after infection. Pretreatment with G-CSF increased hearing loss 24 h after infection and on day 8 compared to untreated rats (Mann-Whitney, P = 0.012 and P = 0.013 respectively). The increased sensorineural hearing loss at day 8 was associated with significantly decreased spiral ganglion cell counts (P = 0.0006), increased damage to the organ of Corti (P = 0.007), increased areas of inflammatory infiltrates (P = 0.02) and increased white blood cell (WBC) counts in cerebrospinal fluid on day 8 after infection (P = 0.0084). Initiation of G-CSF 28 h after infection did not significantly affect hearing loss or cochlear pathology compared to controls. In conclusion, the inflammatory host reaction contributes significantly to the development of hearing loss in experimental meningitis.

Elevated levels of erythrocyte-conjugated dienes indicate increased lipid peroxidation in schistosomiasis mansoni patients.

Schistosoma mansoni causes liver disease by inducing granulomatous inflammation. This favors formation of reactive oxygen species, including superoxide ions, hydrogen peroxide and hydroxyl radicals all of which may induce lipid peroxidation. We have evaluated lipid peroxidation in 18 patients with hepatosplenic schistosomiasis mansoni previously treated with oxamniquine followed by splenectomy, ligature of the left gastric vein and auto-implantation of spleen tissue, by measuring levels of erythrocyte-conjugated dienes and plasma malondialdehyde (MDA). Age-matched, healthy individuals (N = 18) formed the control group. Erythrocyte-conjugated dienes were extracted with dichloromethane/methanol and quantified by UV spectrophotometry, while plasma MDA was measured by reaction with thiobarbituric acid. Patient erythrocytes contained two times more conjugated dienes than control cells (584.5 +/- 67.8 vs 271.7 +/- 20.1 micromol/l, P < 0.001), whereas the increase in plasma MDA concentration (about 10%) was not statistically significant. These elevated conjugated dienes in patients infected by S. mansoni suggest increased lipid peroxidation in cell membranes, although this was not evident when a common marker of oxidative stress, plasma MDA, was measured. Nevertheless, these two markers of lipid peroxidation, circulating MDA and erythrocyte-conjugated dienes, correlated significantly in both patient (r = 0.62; P < 0.01) and control (r = 0.57; P < 0.05) groups. Our data show that patients with schistosomiasis have abnormal lipid peroxidation, with elevated erythrocyte-conjugated dienes implying dysfunctional cell membranes, and also imply that this may be attenuated by the redox capacity of antioxidant agents, which prevent accumulation of plasma MDA.

Elevated levels of erythrocyte-conjugated dienes indicate increased lipid peroxidation in schistosomiasis mansoni patients

Schistosoma mansoni causes liver disease by inducing granulomatous inflammation. This favors formation of reactive oxygen species, including superoxide ions, hydrogen peroxide and hydroxyl radicals all of which may induce lipid peroxidation. We have evaluated lipid peroxidation in 18 patients with hepatosplenic schistosomiasis mansoni previously treated with oxamniquine followed by splenectomy, ligature of the left gastric vein and auto-implantation of spleen tissue, by measuring levels of erythrocyte-conjugated dienes and plasma malondialdehyde (MDA). Age-matched, healthy individuals (N = 18) formed the control group. Erythrocyte-conjugated dienes were extracted with dichloromethane/methanol and quantified by UV spectrophotometry, while plasma MDA was measured by reaction with thiobarbituric acid. Patient erythrocytes contained two times more conjugated dienes than control cells (584.5 ± 67.8 vs 271.7 ± 20.1 æmol/l, P < 0.001), whereas the increase in plasma MDA concentration (about 10 percent) was not statistically significant. These elevated conjugated dienes in patients infected by S. mansoni suggest increased lipid peroxidation in cell membranes, although this was not evident when a common marker of oxidative stress, plasma MDA, was measured. Nevertheless, these two markers of lipid peroxidation, circulating MDA and erythrocyte-conjugated dienes, correlated significantly in both patient (r = 0.62; P < 0.01) and control (r = 0.57; P < 0.05) groups. Our data show that patients with schistosomiasis have abnormal lipid peroxidation, with elevated erythrocyte-conjugated dienes implying dysfunctional cell membranes, and also imply that this may be attenuated by the redox capacity of antioxidant agents, which prevent accumulation of plasma MDA.

Surgical hepatosplenic mansonic schistosomiasis in adolescents: repercussions of the post-treatment schistosomotic burden on the hepatic functional reserve.

Schistosomiasis mansoni affects the hepatic functional reserve. Clinical treatment with oxamniquine is not 100% effective and there has been found strain of this parasite resistant to this drug. The aims of this investigation were: (1) to examine the presence of residual parasite burden after medical and surgical treatment on adolescents with surgical schistosomiasis mansoni and (2) to assess the effect on the hepatic functional reserve in patients with and without residual infection. Twenty nine children with hepatosplenic schistosomiasis mansoni and bleeding esophageal varices were treated with oxamniquine. They underwent splenectomy, ligature of the left gastric vein and autologous implantation of spleen tissue into the greater omentum. After a mean post-operative follow up of five years they underwent rectal biopsy for schistosomotic egg search. They were divided in patients with and without infection. In 20 patients the submucosal egg search was negative, however, in 9 it was positive. The hepatic functional reserve in the patients without infection was as follows: 17 were Child-Pugh A and 3 Child-Pugh B. In the patients who were still infected 6 were Child-Pugh A and 3 Child-Pugh B. The chi2 analysis of the hepatic functional reserve showed chi2 = 3.19 - p= 0.07. From the results the following conclusion can be drawn: residual infection or reinfection in the follow up period had not interfered with the distribution of the hepatic functional reserve of the patients in this series. However, there was a trend for a decrease of this parameter in patients with residual infection.

Autotransplant of spleen tissue in children with schistosomiasis: evaluation of splenic function after splenosis.

Autotransplantation of spleen tissue has been done, in the past ten years, in children with schistosomiasis mansoni with bleeding varices. The purposes of this investigation were: (1) to study the morphology and function of the remnant spleen tissue; (2) to quantify the production of tuftsin; and (3) to assess the immune response to pneumococcal vaccine of these patients. Twenty three children, who underwent splenectomy and autologous implantation of spleen tissue into the greater omentum were included in this investigation. The average postoperative follow-up is five years. Splenosis was proved by colloid liver-spleen scans. Search for Howell-Jolly bodies assessed the filtration function. Tuftsin and the titer of pneumococcal antibodies were quantified by ELISA. Splenosis was evident in all children; however, it was insufficient in two. Howell-Jolly bodies were found only in these two patients. The mean tuftsin serum concentration (335.0 +/- 29.8 ng/ml) was inside the normal range. The immune response to pneumococcal vaccination was adequate in 15 patients; intermediate in four; and inadequate in four. From the results the following conclusions can be drawn: splenosis was efficient in maintaining the filtration splenic function in more than 90% and produced tuftsin inside the range of normality. It also provided the immunologic splenic response to pneumococcal vaccination in 65% of the patients of this series.

[Phlebitis due to venous catheters. Causes and occurrence]. / Venfloninduceret flebit. Arsager og hyppighed.

Seventy-nine patients admitted to Frederiksberg Hospital had peripheral intravenous catheters inserted to aid treatment. We followed the patients in order to determine the frequency of phlebitis, and to isolate mechanical and chemical parameters that increase the risk of phlebitis. The frequency of phlebitis was 27.8%. We found that 35.8% of all complications evolve when the catheter has been inserted for more than 72 hours, and that 45.5% of patients treated with antibiotics develop phlebitis. Furthermore, it seems that acetyl salicylic acid reduces the number of cases with phlebitis. Catheters inserted around the wrist have a higher frequency of phlebitis. Changing the catheters every 72 hours significantly reduces the frequency of phlebitis by 40%. The risk of developing a septic condition due to catheter-induced phlebitis seems small because we suggest that phlebitis is an inflammatory reaction to the plastic-catheter, and not infectious.

Densities of nitric oxide synthesizing nerves in smooth muscles of human gut during fetal development.

BACKGROUND/PURPOSE: Nitric oxide (NO) plays a role in inhibitory neurotransmission in the sphincteric and nonsphincteric smooth muscles. However, the relative contribution of NO synthesizing innervation to these functionally diverse parts of the gut, particularly during development, is unknown. METHODS: Gastrointestinal sphincters and adjoining nonsphincteric bowel segments were obtained from 14 human fetuses (gestation, 12 to 23 weeks). NO synthesizing nerves were examined by nicotinamide adenine deoxinucleotide phosphate (NADPH) diaphorase histochemistry. The densities of NADPH-positive nerves in the smooth muscles were quantified using a computerized image analyzing system on random sections. RESULTS: The NO synthesizing nerve density in intestinal smooth muscles decreased during fetal development as a result of increased interspacing between myenteric ganglia and a disproportionately larger increase in smooth muscle area than neuronal area. The nerve densities were lower in sphincteric regions than the adjoining nonsphincteric regions at the same gestation. CONCLUSION: These findings may have relevance to the occurrence of congenital dysmotility disorders of the sphincteric regions.

Anti-interleukin-8 monoclonal antibody reduces free radical production and improves hemodynamics and survival rate in endotoxic shock in rabbits.

BACKGROUND: Although high levels of interleukin-8 (IL-8) have been found in patients with sepsis and a monoclonal antibody (MoAb) against IL-8 has been successfully used in some animal models of inflammation, no specific therapeutic agent against IL-8 has been tested for the treatment of sepsis. We studied the effects of a MoAb against IL-8 in the treatment of endotoxic shock with a prospective randomized rabbit endotoxic shock model. METHODS: Twenty New Zealand white rabbits were anesthetized and divided into four groups: normal, anti-IL-8, control-Ab, and lipopolysaccharide (LPS). Anti-IL-8 and control-Ab groups received a MoAb (immunoglobulin G, 3 mg/kg) 5 minutes before the LPS injection. All groups, except the normal group, received a continuous 20-minute infusion of LPS (500 micrograms/kg). The normal group received NaCl (0.9%) rather than LPS. RESULTS: The 7-day survival rates were 100% for normal group, 80% for anti-IL-8 group, 40% for control-Ab group, and 0% for LPS group. Compared with the LPS group, anti-IL-8 rabbits had a smaller decrease in mean arterial blood pressure (p < 0.05) and increased urinary volume (p < 0.05). Anti-IL-8 rabbits had lower plasmatic levels of IL-1 beta, less free radical production (p < 0.05), and a higher survival rate (p < 0.01). CONCLUSIONS: IL-8 plays a significant role in endotoxic shock, and IL-8 blockage results in attenuation of the hypotensive and tachypneic effects of LPS, reduced free radical production, and an increased survival rate after lethal endotoxic shock.

Nitrergic innervation of the human gut during early fetal development.

Classically, development of the human enteric nervous system has been characterized by the early appearance (between 9 and 12 weeks' gestation) of adrenergic and cholinergic nerves. The development of peptidergic innervation occurs much later. Recent studies have indicated that nitric oxide is involved in the nonadrenergic noncholinergic innervation of the gut, mediating its relaxation. The authors have investigated the ontogeny of nitrergic (nitric oxide synthase-containing) neurons of the developing gut. Bowel segments from the esophagus, pylorus, and ileocecal and rectosigmoid regions of 14 fetuses (gestational age range, 12 to 23 weeks) were studied with nicotinamide adenosine dinucleotide phosphate (NADPH) diaphorase histochemistry. By 12 weeks' gestation, nitrergic neurons had appeared in the myenteric ganglia, at all levels of the gut, and had begun plexus formation. Nitrergic innervation in the submucous plexus becomes evident after 14 weeks. As gestational age increases, nitrergic innervation becomes richer and more organized. Increasing numbers of nitrergic nerve fibers are seen in the circular muscle; some of these fibers project from the myenteric plexus. By 23 weeks' gestation, nitrergic innervation has matured to the pattern observed in the postnatal gut. Thus, the onset and pace of development of nitrergic innervation are similar to adrenergic and cholinergic innervation and occur before peptidergic innervation. This study provides morphological evidence of the ontogenetic significance of nitrergic innervation in the human gut and supports previous suggestions that nitric oxide has a pathophysiological role in developmental gut motility disorders.

Surgical hepatosplenic schistosomiasis mansoni in children: a Doppler duplex study of the portal vein and the hepatic artery.

From January 1990 to September 1993, 25 children with hepatosplenic schistosomiasis mansoni and oesophageal varices underwent splenectomy, ligature of the left gastric vein and autoimplantation of 100 g of spleen into the great omentum at the University Hospital, Recife, Brazil. The diameters and the blood flow velocities of the portal vein and the hepatic artery were measured before and after surgery. A Doppler Duplex (Aloka 680) with a convex transductor of 3.5 MHz was used. Post-operative follow-up revealed (i) a significant decrease in the mean diameter of the portal vein from 12.6 +/- 2.1 mm to 9.6 +/- 1.9 mm, (ii) a significant increase in the mean diameter of the hepatic artery from 5.0 +/- 1.4 mm to 5.3 +/- 1.2 mm, (iii) a significant decrease in the mean blood flow velocity in the portal vein from 31.1 +/- 8.0 cm/s to 22.4 +/- 7.1 cm/s, and (iv) no significant change in blood flow velocity in the hepatic artery. The study supports the concept that surgical treatment for portal hypertension in patients with hepatosplenic schistosomiasis mansoni, which includes splenectomy, results in a decrease of venous portal blood flow to the liver associated with an increase in the arterial hepatic blood flow. The physiological implications of these haemodynamic changes in the long term remain to be investigated.

Hipertensäo portal esquistossomótica na criança-avaliaçäo critica / Schistomotic portal hypertension in children-Critical evaluation

Esplenectomia, ligadura de veia gástrica esquerda e auto-implante esplênico tem sido a conduta cirúrgica adotada para as crianças portadoras de hepato-esplenomegalia esquistossomótica, com indicaçäo cirúrgica. A esclerose endoscópica das varizes esofageanas é reservada para os casos de recidiva. Quarenta crianças, sendo vinte e três do sexo masculino e dezessete do sexo feminino, portadoras de esquistossomose hepatoesplênica com varizes esofageanas, foram submetidas a esta conduta, entre janeiro de 1990 e dezembro de 1994. Após seguimento pós-operatório médio de 36 meses, houve recidiva hemorrágica em três pacientes, com controle do sangramento por escleroterapia endoscópica das varizes esofageanas. No seguimento endoscópico houve o desaparecimento das varizes em cinco pacientes e reduçäo das varizes de grosso para médio calibres em oito dos dezesseis pacientes. Entretanto, a análise estatística näo revelou diferença significativa entre a frequência dos graus das varizes antes do tratamento e por ocasiäo da última valiaçäo endoscópica. A evoluçäo clínica dos pacientes faz supor que a conduta proposta tenha, até o momento, sido efetiva

Human gastrointestinal sphincters: study on the maturation of the nitric oxide innervation

Estudos histoqyímicos relevam uma inervaçäo noradrenérgica dos esfincteres gastrointestinais mais densa do que as regiöes näo-esfincterianas. também tem sido mostrado uma rica rede interconectante de fibras nervosas óxido-nitrérgicas inibitórias adivindas da gânglia mioentérica e se distribuindo dentro da camada muscular circular, especialmente nas regioSes esfincterianas. a presente investigaçäo estudou, no intestino humano em desenvolvimento, a histomorfometria da inervaçäo óxido-nitrérgica diárias intestinais selecionadas, particularmente, das regiSes esfincterianas. Segmnetos da junçäo gastro-esofagiana, regiäo gastro-piloro-duodenal, regiäo íleo-cecal e reto distal de 14 fetos de idade gestacional entre 12 e 23 semanas, foram usados para mapeamento histoquímico da nicotinamida adenosina de óxido nuleotídeo fosfato diaforase. Imagens de secçSes randonizadas foram selecionadas para histofometria, usando um sistema computadorizado de análise de imagens. A partir dos resultados, as seguintes conclusSes foram tiradas: 1- existe uma rede muito rica em nervos óxido-nitrérgicos interconectado a gânglia mioentérica e a camada muscular circular de todos os níveis selecionados. sendo mais densa na junçäo gastro-esofagiana, piloro, junçäo íleo-cecal e esfincter anal interno; 2- existe uma correlaçäo linear negativa entre a atividade neuronal mioentérica óxido-nitrérgica (densidade ganglionar) e a idade gestacional, a qual pode ser expressa pela equaçäo: Densidade ganglionar = 30,158- 1,0313 x idade gestacional. O esôfago, o piloro e esfíncter anal interno foram as regiöes com as mais baixas densidades ganglionares. Esses achados sugerem que a inervaçäo óxodo-nitrergica naqulas áreas, associada com densidade ganglionares relativamente baixas, torna possível levantar a hipótese de ue a normalidade ou retardo da maturaçäo desta inervaçäo inibitória poderia estar envolvida na patogênes de algumas anomalias congênitas como a estemose hipertrófica do piloro e acalásia do esfíncter anal interno

Síndrome de budd-chiari após transplante de fígado de tamanho reduzido / Budd-Chiari syndrome sfter liver transplantation of the size reduction

Um caso de síndrome de Budd-Chiari desenvolvido em uma criança de dois anos primariamente portadora de atresia de vias biliares, logo após ter se submetido a um transplante hepático em que foi usado o segmento lateral esquerdo do fígado de um doador de 54 anos, é relatado. A maior susceptibilidade a complicaçöes vasculares, após transplante de segmentos de fígado, por inadequaçäo conteúdo-continente é assinalada. O transplante com o fígado total de doador de dois anos foi a soluçäo final para a insuficiência hepato-renal desenvolvida a partir do acotovelamento da anastomose da veia hepática esquerda-cava inferior com consequente necrose hepática maciça, hemorragia e trombose das veias centro-lobulares. O relato é original na literatura

Splenic embolization in children: long-term efficacy.

Eighteen partial splenic embolization procedures (PSEs) were performed in 17 children for hypersplenism (13) and/or esophageal variceal hemorrhage (12). The underlying disease was biliary atresia (BA) in nine children, portal vein thrombosis (PVT) in four, and biliary cirrhosis (BC) in four. From 20% to 90% of the spleen was embolized. Immediate morbidity was high, albeit minor, and the initial hospitalization was protracted for an average of 16 days. The children were followed from 4 to 81 months (average, 34.2). Four patients with BA patients subsequently had liver transplantation at an average of 20 months after PSE. In ten of 13 patients with hypersplenism, hematologic indexes returned to and remained normal throughout follow-up. The three exceptional patients (who had only 20%, 60% and 60% splenic embolization) developed recurrent mild hypersplenism, one of whom was reembolized and is free from hypersplenism 22 months later. Variceal hemorrhage was ameliorated in all 12 patients (average, 2.4 episodes of hemorrhage per year before PSE, 0.5 per year afterwards). Overwhelming postsplenectomy sepsis did not occur in an aggregate follow-up of 48.5 years. PSE is a legitimate treatment alternative for hypersplenism and for esophageal varices in children.