Pediatric traumatic hemorrhagic shock consensus conference recommendations.

ABSTRACT: Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization of prehospital blood products, (3) use of hemostatic adjuncts, (4) tourniquet use, (5) prehospital airway and blood pressure management, and (6) conventional coagulation tests or thromboelastography-guided resuscitation. A total of 21 recommendations are detailed in this article: 2 clinical recommendations, 14 expert consensus statements, and 5 good practice statements. The statement, the panel's voting outcome, and the rationale for each statement intend to give pediatric trauma providers the latest evidence and guidance to care for pediatric trauma patients experiencing hemorrhagic shock. With a broad multidisciplinary representation, the Pediatric Traumatic Hemorrhagic Shock Consensus Conference systematically evaluated the literature and developed clinical recommendations, expert consensus, and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock.

Blood banking considerations in pediatric trauma.

ABSTRACT: Transfusion of blood products to a hemorrhaging pediatric trauma patient requires seamless partnership and communication between trauma, emergency department, critical care, and transfusion team members. To avoid confusion and delays, understanding of blood banking principles and mutually agreed upon procedures and policies must be regularly updated as knowledge evolves. Because pediatric patients require specialized considerations distinct from those in adults, this brief review covers transfusion principles, policies, and procedures specific to the resuscitation of pediatric trauma patients.

Pediatric traumatic hemorrhagic shock consensus conference research priorities.

BACKGROUND: Traumatic injury is the leading cause of death in children and adolescents. Hemorrhagic shock remains a common and preventable cause of death in the pediatric trauma patients. A paucity of high-quality evidence is available to guide specific aspects of hemorrhage control in this population. We sought to identify high-priority research topics for the care of pediatric trauma patients in hemorrhagic shock. METHODS: A panel of 16 consensus multidisciplinary committee members from the Pediatric Traumatic Hemorrhagic Shock Consensus Conference developed research priorities for addressing knowledge gaps in the care of injured children and adolescents in hemorrhagic shock. These ideas were informed by a systematic review of topics in this area and a discussion of these areas in the consensus conference. Research priorities were synthesized along themes and prioritized by anonymous voting. RESULTS: Eleven research priorities that warrant additional investigation were identified by the consensus committee. Areas of proposed study included well-designed clinical trials and evaluations, including increasing the speed and accuracy of identifying and treating hemorrhagic shock, defining the role of whole blood and tranexamic acid use, and assessment of the utility and appropriate use of viscoelastic techniques during early resuscitation. The committee recommended the need to standardize essential definitions, data elements, and data collection to facilitate research in this area. CONCLUSION: Research gaps remain in many areas related to the care of hemorrhagic shock after pediatric injury. Addressing these gaps is needed to develop improved evidence-based recommendations for the care of pediatric trauma patients in hemorrhagic shock.

Lung T-Cell Profile Alterations are Associated with Bronchiolitis Obliterans Syndrome in Cystic Fibrosis Lung Transplant Recipients.

The contribution of T-cells after lung transplant (LTx) remains controversial with no current consensus of their role concerning chronic lung allograft dysfunction. Using flow cytometry to assess T-cell subsets of bronchoalveolar lavage fluid (BALF) in 16 cystic fibrosis (CF) LTx recipients, we identified a decline in CD4+ T-cell frequency and an increase in CD8+ T-cell frequency in patients who developed severe bronchiolitis obliterans syndrome (BOS) (N = 10) when comparing baseline (6 months post-LTx) and follow-up (most recent bronchoscopy-clinical or surveillance per protocol). Comparing BOS to No BOS cohorts, significant differences were found in CD4+ T-cell frequency [17.4 (12.5, 28.2) vs 46.6 (44.4, 48.4), p = 0.003] and CD8+ T-cell frequency [65.6 (62.8, 75.3) vs 39.2 (32.2, 43.3), p = 0.014], respectively. The mean difference of the CD4:CD8 ratio was 0.87 units lower (95% CI - 1.44 to - 0.30, p = 0.006) than patients without BOS, while the median difference of the CD4:CD8 ratio was 0.92 units lower (95% CI - 1.83 to - 0.009, p = 0.048). Therefore, our results suggest that T-cell profiles measured through flow cytometry of BALF in the CF LTx population are associated with the development of severe BOS. Further work is needed in larger patient populations to validate our findings and to determine if this is useful for recipients who underwent LTx for other indications.

Refractory Thrombocytopenia Is a Valid Early Diagnostic Criteria for Hepatic Veno-Occlusive Disease in Children.

We compared the incidence of refractory thrombocytopenia (RT) and platelet transfusion requirements (PTR) in 35 children who developed veno-occlusive disease (VOD) with 35 matched control subjects who underwent hematopoietic stem cell transplant but did not develop VOD. RT developed in 100% of the VOD patients, at a median of 8 days before VOD diagnosis, as compared with 71.5% of the control group. VOD patients required more platelet transfusions than control subjects (median PTR, 6.9 mL/kg [range, .57 to 17.59] versus 3.57 mL/kg [range, 0 to 14.63], respectively) with a statistically significant difference (P < .0001). The number of days with platelet requirements was significantly higher for VOD patients as compared with control subjects (median 68% versus 39%, P =< .0001). The PTR peaked at ~12 mL/kg/day, 2 days before VOD diagnosis, whereas the PTR in the control population was 5 mL/kg/day. The positive predictive value of developing VOD was 88.9% (95% confidence interval, 66.5% to 97%) in patients who were given >7 mL/kg/day of platelets during the at-risk period of days +3 to +13 after transplant. For patients who received >8 mL/kg/day of platelets, the positive predictive value of developing VOD was 86.7% (95% confidence interval, 61.2% to 96.4%). There was no difference in the PTR in patients with mild to moderate VOD as compared with severe VOD; however, the PTR was higher in patients whose VOD did not resolve. The median daily PTR after the diagnosis of VOD in 17 patients who got defibrotide as compared with those who did not get defibrotide was 6.04 mL/kg and 5.72 mL/kg, respectively, but the difference was not statistically significant (P = .56). On univariate and multivariate analysis use of intravenous immunoglobulin was significantly associated with VOD (P = .0088) but was not significantly associated with fatal VOD. In conclusion, RT occurs in 100% of patients at a median of 8 days before VOD diagnosis. VOD should be suspected in any patient with RT after the exclusion of other causes of consumptive thrombocytopenia, especially if they require >7 mL/kg/day of platelets.

Cytoplasmic Fibrillar Aggregates in Gallbladder Epithelium Are a Frequent Mimic of Cystoisospora in Pediatric Cholecystectomy Specimens.

CONTEXT.­: Cystoisospora belli is an intracellular parasite associated with gastrointestinal disease in immunocompromised hosts. Although infection has been classically associated with intestinal disease, studies have identified Cystoisospora in the gallbladder of immunocompetent patients based on hematoxylin-eosin morphology. Recently, the identity of this histologic finding as Cystoisospora has been questioned based on negative results of nucleic acid studies. OBJECTIVE.­: To determine the prevalence of this histologic feature in pediatric patients, we retrospectively reviewed all cholecystectomy specimens from a pediatric hospital during a 24-month period. DESIGN.­: In 180 cholecystectomy specimens, we identified 11 cases (6.1%) with classical histologic features previously described to represent Cystoisospora organisms. To further investigate these structures, we retrieved tissue from paraffin-embedded blocks and performed electron microscopy. RESULTS.­: Ultrastructural examination identified ovoid perinuclear cytoplasmic structures composed of dense fibrillar aggregates rather than organisms. Patients with positive cases were similar in age to controls (positive cases: mean patient age 13.4 years [range, 2-23 years]; negative cases: mean patient age 14.7 years [range, 12 weeks-31 years]; P = .35). There was no significant association of this finding with cholelithiasis (54.5% versus 65.1%, P = .52), cholesterolosis (0% versus 22.5%, P = .12), acute cholecystitis (9.1% versus 10.1%, P > .99), or chronic cholecystitis (45.5% versus 66.3%, P = .20). CONCLUSIONS.­: To our knowledge, this is the first positive identification of these structures as cytoplasmic fibrillar aggregates rather than parasitic inclusions by ultrastructural examination, and the first study of this histologic finding in pediatric cholecystectomies.

Plasma Free Hemoglobin Generation Using the EOS PMP™ Oxygenator and the CentriMag® Blood Pump.

Hemolysis is a known consequence of extracorporeal membrane oxygenation (ECMO) resulting from shear force within the different components of the extracorporeal circuit. The primary aim of this study was to evaluate the EOS PMP™ oxygenator for generation of plasma free hemoglobin (PfHg) over 24 hours at nominal operating range flow rates. The EOS ECMO™ (LivaNova, Inc.; formerly Sorin, Arvada, CO) is equipped with a plasma tight polymethylpentene (PMP) hollow fiber oxygenator. We hypothesized that PfHg generation would be elevated in circuits with higher flow rates, because of the significant pressure drop across the oxygenator according to manufacturer provided flow charts. Generated PfHg concentrations were compared with PfHg concentrations from blood not exposed to an ECMO circuit. The secondary aim was to evaluate circuit flow-rate-induced changes in platelet count and platelet function over 24 hours. Circuits contained a CentriMag® (St. Jude Medical, St. Paul, MN) blood pump and an EOS ECMO PMP™ oxygenator. Circuits in triplicate were run continuously for 24 hours at three flow rates [1, 3, and 5 liters per minute {LPM}]. PfHg was analyzed at baseline, 6, 12, 18, and 24 hours. Platelet count and function were measured at baseline and 24 hours. Concentrations of PfHg at baseline for circuits operating at 1, 3, and 5 LPM were 24.4 ± 4.0, 38.4 ± 28.6, and 26.7 ± 6.9 mg/dL, respectively. PfHg concentrations after 24 hours were statistically compared for the three flow rates using analysis of variance; PfHg concentrations at 1 LPM (181.4 ± 29.1 mg/dL), 3 LPM (145.9 ± 8.7 mg/dL), and 5 LPM (100.1 ± 111.3 mg/dL) circuits. The F-test was not statistically significant (p = .632), indicating that PfHg generation at 24 hours was similar among the three flow rates. Excessive hemolysis using PfHg levels in the EOS PMP™ membrane oxygenator was not observed.

Classification of Indeterminate Melanocytic Lesions by MicroRNA Profiling.

PURPOSE: Identification of indeterminate melanocytic skin lesions capable of neoplastic progression is suboptimal and may potentially result in unnecessary morbidity from surgery. MicroRNAs (miRs) may be useful in classifying indeterminate Spitz tumors as having high or low risk for malignant behavior. METHODS: RNA was extracted from paraffin-embedded tissues of benign nevi, benign Spitz tumors, indeterminate Spitz tumors, and Spitzoid melanomas in adults (n = 62) and children (n = 28). The expression profile of 12 miRs in adults (6 miRs in children) was analyzed by real-time polymerase chain reaction. RESULTS: Benign Spitz lesions were characterized by decreased expression of miR-125b and miR-211, and upregulation of miR-22, compared with benign nevi (p < 0.05). A comparison of Spitzoid melanomas to benign nevi revealed overexpression of miR-21, miR-150, and miR-155 in the malignant primaries (p < 0.05). In adults, Spitzoid melanomas exhibited upregulation of miR-21, miR-150, and miR-155 compared with indeterminate Spitz lesions. Indeterminate Spitz lesions with low-risk pathologic features had lower miR-21 and miR-155 expression compared with Spitzoid melanoma tumors in adults (p < 0.05), while pathologic high-risk indeterminate Spitz lesions had increased levels of miR-200c expression compared with low-risk indeterminate lesions (p < 0.05). Pediatric Spitzoid melanomas exhibited increased miR-21 expression compared with indeterminate Spitz lesions (p < 0.05). Moreover, miR-155 expression was increased in indeterminate lesions with mitotic counts >1 and depth of invasion >1 mm, suggesting miR-155 expression is associated with histological characteristics. CONCLUSIONS: miR expression profiles can be measured in indeterminate Spitz tumors and correlate with markers of malignant potential.

Transfusion with packed red blood cells while awaiting lung transplantation is associated with reduced survival after lung transplantation.

BACKGROUND: The effect of pretransplant transfusion of red blood cells on survival after lung transplantation (LTx) has not been studied. METHODS: The UNOS database was queried from 2005 to 2013 to compare survival in recipients receiving a transfusion while on the LTx wait list. RESULTS: Of 12 283 adult patients undergoing single or bilateral LTx from May 2005 onwards, 11 801 met inclusion criteria, among whom 512 required transfusion while on the LTx wait list. Transfusion was associated with a higher mortality hazard in unadjusted Cox proportional hazards analysis (HR=1.296; 95% CI: 1.124, 1.494; P<.001), and in a multivariable Cox model (HR=1.178; 95% CI: 1.013, 1.369; P=.033) after multiple imputation was used to complete data on covariates. Propensity score matching was used to match transfusion recipients to nonrecipients on the likelihood of having received transfusions on the wait list, calculated from characteristics at the time of listing. Unadjusted Cox regression stratified on the matched pairs also demonstrated an association between transfusion receipt on the wait list and higher post-transplant mortality hazard (HR=1.494; 95% CI: 1.127, 1.979; P=.005). CONCLUSIONS: Blood transfusion while on the LTx wait list was associated with diminished patient survival after transplantation.

The Bethesda System for Reporting Thyroid Cytopathology is applicable to frozen section diagnosis in children.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) offers standardized and widely understood diagnostic categories for reporting thyroid cytology diagnoses. We compared the utility of TBSRTC categories in pediatric cytology diagnoses and pediatric intraoperative frozen section diagnoses. We examined the experience of our primary and referral care center over a 20-year period. This included 182 thyroidectomy patients who underwent 64 preoperative fine-needle aspirations and 91 intraoperative frozen section evaluations, including 38 patients evaluated sequentially by each method. All diagnoses were retrospectively reclassified into TBSRTC categories and correlated with the final thyroidectomy diagnoses. For each sampling method, malignant final diagnoses were observed at similar frequencies to rates predicted by TBSRTC. Malignant final diagnoses following fine-needle aspiration or frozen section diagnoses in TBSRTC categories other than malignant or suspicious for malignancy most often resulted from difficulty in detecting papillary carcinoma, including difficulty detecting the nuclear characteristics of papillary carcinoma in frozen sections. The limitations of needle biopsy and frozen section evaluations differ, yet serial utilization of these procedures was rarely informative. Based on the experience of our institution, classification of cytology and frozen section diagnosis by TBSRTC predicts a risk of malignancy similar to the guidance offered by TBSRTC. We recommend including a TBSRTC category when reporting either thyroid cytology or frozen section diagnoses in children.

The College of American Pathologists guidelines for whole slide imaging validation are feasible for pediatric pathology: a pediatric pathology practice experience.

Whole slide imaging (WSI) is rapidly transforming educational and diagnostic pathology services. Recently, the College of American Pathologists Pathology and Laboratory Quality Center (CAP-PLQC) published recommended guidelines for validating diagnostic WSI. We prospectively evaluated the guidelines to determine their utility in validating pediatric surgical pathology and cytopathology specimens. Our validation included varied pediatric specimen types, including complex or less common diagnoses, in accordance with the guidelines. We completed WSI review of 60 surgical pathology cases and attempted WSI review of 21 cytopathology cases. For surgical pathology cases, WSI diagnoses were highly concordant with glass slide diagnoses; a discordant diagnosis was observed in 1 of 60 cases (98.3% concordance). We found that nucleated red blood cells and eosinophilic granular bodies represented specific challenges to WSI review of pediatric specimens. Cytology specimens were more frequently discordant or failed for technical reasons, with overall concordance of 66.7%. Review of pediatric cytopathology specimens will likely require image capture in multiple focal planes. This study is the first to specifically evaluate WSI review for pediatric specimens and demonstrates that specimens representing the spectrum of pediatric surgical pathology practice can be reviewed using WSI. Our application of the proposed CAP-PLQC guidelines to pediatric surgical pathology specimens is, to our knowledge, the first prospective implementation of the CAP-PLQC guidelines.

Plasma exchange on venovenous extracorporeal membrane oxygenation with bivalirudin anticoagulation.

A pediatric patient requiring venovenous (VV) extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation developed heparin-induced thrombocytopenia. Unfractionated heparin was discontinued, and a bivalirudin infusion was started. During the lung transplant evaluation, he was found to have allosensitization, requiring treatment with plasma exchange along with pulse methylprednisolone, rituximab, bortezomib, and pooled immunoglobulin infusion. We describe our experience with successful plasma exchange for allosensitization during bivalirudin anticoagulation on VV ECMO in a pediatric patient.

Quality improvement methodologies increase autologous blood product administration.

Whole blood from the heart-lung (bypass) machine may be processed through a cell salvaging device (i.e., cell saver [CS]) and subsequently administered to the patient during cardiac surgery. It was determined at our institution that CS volume was being discarded. A multidisciplinary team consisting of anesthesiologists, perfusionists, intensive care physicians, quality improvement (QI) professionals, and bedside nurses met to determine the challenges surrounding autologous blood delivery in its entirety. A review of cardiac surgery patients' charts (n = 21) was conducted for analysis of CS waste. After identification of practices that were leading to CS waste, interventions were designed and implemented. Fishbone diagram, key driver diagram, Plan-Do-Study-Act (PDSA) cycles, and data collection forms were used throughout this QI process to track and guide progress regarding CS waste. Of patients under 6 kg (n = 5), 80% had wasted CS blood before interventions, whereas those patients larger than 36 kg (n = 8) had 25% wasted CS before interventions. Seventy-five percent of patients under 6 kg who had wasted CS blood received packed red blood cell transfusions in the cardiothoracic intensive care unit within 24 hours of their operation. After data collection and didactic education sessions (PDSA Cycle I), CS blood volume waste was reduced to 5% in all patients. Identification and analysis of the root cause followed by implementation of education, training, and management of change (PDSA Cycle II) resulted in successful use of 100% of all CS blood volume.

Hyperbilirubinemia complicating plasma-free hemoglobin and antifactor Xa level monitoring on venovenous extracorporeal membrane oxygenation.

Optical spectrophotometric methods are used to detect both plasma-free hemoglobin and antifactor Xa level, so hyperbilirubinemia can interfere with the measurement of both the monitoring laboratory tests for extracorporeal membrane oxygenation (ECMO) due to similar absorbance wavelengths. We present a seven-year-old child with acute respiratory failure on venovenous ECMO who developed an acute increase in plasma-free hemoglobin and undetectable antifactor Xa level due to acute hyperbilirubinemia from hepatic dysfunction related to antifungal therapy.

Interstitial lung disease in a child with antisynthetase syndrome.

INTRODUCTION: Antisynthetase Syndrome is associated with interstitial lung disease in adult patients, but this has not been described in children. MATERIALS AND METHODS: A 13-year-old with interstitial lung disease due to Antisynthetase Syndrome and pulmonary arterial hypertension underwent emergent bilateral lung transplantation after a rapid clinical decline. CONCLUSION: We present the clinical, radiographic, and histological findings of a child with interstitial lung disease due to Antisynthetase Syndrome.