Lama Elbahlawan

Heat shock protein 70-2+1267 AA homozygotes have an increased risk of septic shock in adults with community-acquired pneumonia

ObjectiveHeat shock protein (HSP)70-2 is an important immunomodulatory protein induced in response to inflammatory stimuli. We assessed whether HSP70-2+1267 genotype influenced the risk of septic shock in a prospective cohort study of community-acquired pneumonia and whether HSP70-2+1267 genotype is a better predictor of septic shock than the genotype at lymphotoxin-&agr; +250. DesignProspective cohort study. SettingA large, nonprofit, private hospital system in Memphis, TN. PatientsAdults admitted with community-acquired pneumonia between 1998 and 2001. Septic shock was defined according to consensus criteria (American College of Chest Physicians/Society of Critical Care Medicine, 1992). InterventionsBlood sampling. Measurements and Main ResultsA total of 343 subjects were enrolled; 30 had septic shock. HSP70-2+1267 and lymphotoxin-&agr; +250 genotype was determined using polymerase chain reaction and restriction enzyme digestion. HSP70-2+1267 AA genotype was the strongest predictor of septic shock (p = .0005; relative risk, 3.5). Lymphotoxin-&agr; +250 AA genotype was also associated with an increased risk of septic shock (p = .002; relative risk, 2.7). Logistic regression analysis found only age (p = .04) and HSP70-2+1267 genotype (p = .006) were predictors of septic shock. The greatest risk of septic shock was associated with carriage of the HSP70-2+1267 A/lymphotoxin-&agr; +250 A haplotype (p < .0001). ConclusionsHSP70-2+1267 genotype is a stronger predictor of septic shock in patients with community-acquired pneumonia than lymphotoxin-&agr; +250 genotype.

Outcomes of hematopoietic stem cell transplant patients who received continuous renal replacement therapy in a pediatric oncology intensive care unit

Objectives: To assess the long-term benefits of continuous renal replacement therapy (CRRT) in this patient population and to analyze factors associated with survival. Hematopoietic stem cell transplantation is being utilized as curative therapy for a variety of disorders. However, organ dysfunction is commonly associated with this therapy. Continuous renal replacement therapy (CRRT) is increasingly being used in the treatment of this multiorgan dysfunction. Design: Retrospective cohort study. Setting: A free-standing, tertiary care, pediatric oncology hospital. Patients: Twenty-nine allogeneic hematopoietic stem cell transplantation patients who underwent 33 courses of CRRT in the intensive care unit between January 2003 and December 2007. Interventions: Cox proportional hazards regressions models were used to examine the relationship between demographic and clinical variables and length of survival. Measurements and Main Results: The median length of survival post CRRT initiation was 31 days; only one patient survived >6 mos. Factors associated with increased risk of death included: higher bilirubin and blood urea nitrogen levels before and at 48 hrs into CRRT, lower Pao2/Fio2 ratios at 48 hrs of CRRT, and higher C-reactive protein levels, as well as lower absolute neutrophil counts at CRRT end. Conclusion: In this single-center study, CRRT was not associated with long-term survival in pediatric allogeneic hematopoietic stem cell transplantation patients. Clinical data exist, both before and during CRRT, that may be associated with length of survival. Lower C-reactive protein levels at CRRT end were associated with longer survival, suggesting that the ability to attenuate inflammation during CRRT may afford a survival advantage. These findings require confirmation in a prospective study. (Pediatr Crit Care Med 2010; 11:699–706)

Impact of continuous renal replacement therapy on oxygenation in children with acute lung injury after allogeneic hematopoietic stem cell transplantation

Acute lung injury (ALI) continues to carry a high mortality rate in children after allogeneic hematopoietic stem cell transplant (HSCT). Continuous renal replacement therapy (CRRT) is often used for these patients for various indications including renal failure and fluid overload, and may have a beneficial effect on oxygenation and survival. Therefore, we sought to determine the effect of CRRT on oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI, and to document survival to intensive care unit discharge in this at‐risk population receiving both mechanical ventilation and CRRT.

β2-Adrenergic receptor polymorphisms in African American children with status asthmaticus

Background: The β2-adrenergic receptor plays a central role in the bronchodilator response to β2-agonists in patients with asthma. Genetic polymorphisms within the gene coding for this receptor influence responsiveness of the receptor. A number of these polymorphisms differ in frequency in the African American and white populations. Objective: To determine the frequency of specific β2-adrenergic receptor polymorphisms in African American children with status asthmaticus and to examine whether a specific genotype is associated with the clinical response to therapy. Design: Cohort of African American children diagnosed with status asthmaticus. Setting: Tertiary care childrens hospital. Patients: A total of 31 African American children with status asthmaticus. Intervention: Blood samples were obtained from children at admission. Genotypes were determined by polymerase chain reaction amplification and restriction enzyme digestion. Main Outcome Measures: The requirement for admission to the pediatric intensive care unit, need for mechanical ventilation, institution of various therapies, and length of stay. Results: The genotypes of the polymorphic sites at amino acid positions 16 and 27 in the β2-adrenergic receptor were determined. There were no significant differences between the various genotypes in the percentage of children requiring pediatric intensive care unit admission, mechanical ventilation, terbutaline treatment, or length of stay. However, in children heterozygous for Glu at position 27 of the β2-adrenergic receptor, the percentage of patients requiring aminophylline treatment, in addition to β2-agonist therapy, was significantly higher than that seen in patients homozygous for Gln at that position (5/10 [50%] vs. 1/21 [5%], respectively; p = .002). Conclusions: African American children with status asthmaticus who have the Gln/Glu genotype at amino acid position 27 of the β2-adrenergic receptor may benefit from aminophylline treatment in addition to β2-agonist therapy.

Severe H1N1-associated acute respiratory failure in immunocompromised children†

Severe pandemic influenza A (H1N1) infection can lead to acute respiratory failure (ARF) with associated high mortality. Children with malignancy may be at higher risk of H1N1‐associated ARF because of underlying primary disease or immunosuppression associated with chemotherapy.

A Critical Care and Transplantation-Based Approach to Acute Respiratory Failure after Hematopoietic Stem Cell Transplantation in Children

Abstract Acute respiratory failure contributes significantly to nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Although there is a trend of improved survival over time, mortality remains unacceptably high. An understanding of the pathophysiology of early respiratory failure, opportunities for targeted therapy, assessment of the patient at risk, optimal use of noninvasive positive pressure ventilation, strategies to improve alveolar recruitment, appropriate fluid management, care of the patient with chronic lung disease, and importantly, a team approach between critical care and transplantation services may improve outcomes.

Association of IL-1β -511 polymorphism with severe veno-occlusive disease in pediatric-matched allogeneic hematopoietic stem cell transplantation.

Single nucleotide polymorphisms (SNPs) of the interleukin 1 (IL-1) family have been implicated in acute graft-versus-host disease and mortality postallogeneic hematopoietic stem cell transplantation (HSCT) in adults. Hepatic veno-occlusive disease (VOD) is a well-known complication of HSCT and can result in an increased risk of mortality. In this study, we sought to investigate the association of both patient and donor genotypes at the IL-1&bgr; −511 cytidine/thymidine (C/T) polymorphic site with hepatic VOD and mortality in an exclusive pediatric cohort undergoing matched myeloablative allogeneic HSCT. Donor TT genotype was associated with higher cumulative incidence of grade III-IV hepatic VOD at 3 months after transplantation relative to donor CT and CC genotypes (25±13.1% in TT, 2.9±2.9% in CT, and 3.6±3.6% in CC; P=0.024). Neither recipient nor donor IL-1&bgr; −511 single nucleotide polymorphisms genotypes were associated with mortality or relapse. Our findings suggest that donor, rather than host, genotype at the IL-1&bgr; −511 polymorphic site may associate with higher risk for severe VOD after matched allogeneic HSCT. Our findings challenge the assumption that host factors are exclusively responsible for VOD and suggest a novel role for the donor inflammasome pathway in inducing injury and microvascular disease after HSCT, which merits further study in a larger cohort analysis.

Impact of neutrophil recovery on oxygenation in pediatric oncology patients with acute hypoxemic respiratory failure.

Neutrophil recovery has been implicated in deterioration of oxygenation and exacerbation of lung injury in pediatric oncology patients. Our objectives were to determine the impact of neutrophil recovery on oxygenation in pediatric oncology patients with acute hypoxemic respiratory failure (AHRF) and to identify risk factors that result in oxygenation worsening. A cohort of 24 neutropenic pediatric oncology patients with AHRF in whom neutrophil recovery occurred during a course of mechanical ventilation was evaluated. Oxygenation index (OI) and PaO2/FiO2 ratio showed a trend of improvement after neutrophil recovery. Mean PaO2/FiO2 pre-recovery was 205±48.67 versus 225±72.24 postrecovery (P=0.08), whereas mean pre-recovery OI was 9.39±0.96 compared with 8.31±1.1 postrecovery (P=0.078). Seven episodes (24% of the total episodes) of recovery were characterized by worsening of oxygenation. Tripling absolute neutrophil count on Day+2 compared with Day+1 postrecovery was associated with 28-fold increase in risk of oxygenation worsening. In conclusion, resolution of neutropenia lead to significant deterioration of oxygenation in 24% of episodes of neutrophil recovery in a pediatric oncology cohort with AHRF. Our findings suggest that a faster ANC increment in the 2 days after recovery is associated with an increased risk of oxygenation worsening.

Continuous Renal Replacement Therapy in Children Post-Hematopoietic Stem Cell Transplantation: The Present and the Future

Allogeneic hematopoietic stem cell transplantation (HSCT) use has expanded markedly to treat different disorders like hematologic malignancies, immunodeficiency, and inborn errors of metabolism. However, it is commonly associated with complications that limit the benefit of this therapy. Acute renal failure occurs commonly after HSCT and results in increased risk of mortality. In many instances, children post-HSCT develop acute renal insufficiency in the context of other organ failure, necessitating intensive care unit admission for management. Recently, continuous renal replacement therapy (CRRT) has emerged as the favored modality of renal replacement therapy in the care of critically ill children who are hemodynamically unstable. Currently, CRRT is being utilized more often in the care of critically ill post- HSCT children to treat renal failure or to prevent fluid overload (FO). FO > 20% has been shown in many studies to be an independent risk of mortality in critically ill children and therefore, many clinicians will initiate this therapy due to FO even without overt renal failure. CRRT may be beneficial in disease processes as acute lung injury due to removal of fluid. CRRT results in improved oxygenation in post-HSCT children with acute lung injury and this improvement is sustained for at least 48 hours after initiation of this therapy. Survival in post-HSCT children requiring this therapy ranges from 17% to 45%, however, long term survival is still poor. This review will discuss current practice of CRRT in children post-HSCT, as well as future directions.

Successful Use of a Rapid Response Team in the Pediatric Oncology Outpatient Setting

In a clinic setting, the RRT, in conjunction with the ICU intensivist, succesfully treated a septic patient with fluid resuscitation and a vasoactive medication, and subsequently facilitated a quick transport to a higher level of care. St. Jude Childrens Research Hospitals successful use of the RRT in the clinic setting suggests that RRTs can be used to improve patient outcomes across the spectrum of inpatient as well as outpatient hospital settings. Our experience suggests that RRTs can be beneficial in filling a gap in patient safety in outpatient clinics.