Being small for gestational age is not an independent risk factor for mortality in neonates with congenital diaphragmatic hernia: a multicenter study.

BACKGROUND: Congenital diaphragmatic hernia (CDH) accounts for 8% of all major congenital anomalies. Neonates who are small for gestational age (SGA) generally have a poorer prognosis. We sought to identify risk factors and variables associated with outcomes in neonates with CDH who are SGA in comparison to neonates who are appropriate for gestational age (AGA). METHODS: We used the multicenter Diaphragmatic Hernia Research & Exploration Advancing Molecular Science (DHREAMS) study to include neonates enrolled from 2005 to 2019. Chi-squared or Fisher's exact tests were used to compare categorical variables and t tests or Wilcoxon rank sum for continuous variables. Cox model analyzed time to event outcomes and logistic regression analyzed binary outcomes. RESULTS: 589 neonates were examined. Ninety were SGA (15.3%). SGA patients were more likely to be female (p = 0.003), have a left sided CDH (p = 0.05), have additional congenital anomalies and be diagnosed with a genetic syndrome (p < 0.001). On initial single-variable analysis, SGA correlated with higher frequency of death prior to discharge (p < 0.001) and supplemental oxygen requirement at 28 days (p = 0.005). Twice as many SGA patients died before repair (12.2% vs 6.4%, p = 0.04). Using unadjusted Cox model, the risk of death prior to discharge among SGA patients was 1.57 times the risk for AGA patients (p = 0.029). There was no correlation between SGA and need for ECMO, pulmonary hypertensive medication at discharge or oxygen at discharge. After adjusting for confounding variables, SGA no longer correlated with mortality prior to discharge or incidence of unrepaired defects but remained significant for oxygen requirement at 28 days (p = 0.03). CONCLUSION: Infants with CDH who are SGA have worse survival and poorer lung function than AGA infants. However, the outcome of SGA neonates is impacted by other factors including gestational age, genetic syndromes, and particularly congenital anomalies that contribute heavily to their poorer prognosis.

Management of blunt pancreatic trauma: what's new?

Pancreatic injuries are relatively uncommon but present a major challenge to the surgeon in terms of both diagnosis and management. Pancreatic injuries are associated with significant mortality, primarily due to associated injuries, and pancreas-specific morbidity, especially in cases of delayed diagnosis. Early diagnosis of pancreatic trauma is a key for optimal management, but remains a challenge even with more advanced imaging modalities. For both penetrating and blunt pancreatic injuries, the presence of main pancreatic ductal injury is the major determinant of morbidity and the major factor guiding management decisions. For main pancreatic ductal injury, surgery remains the preferred approach with distal pancreatectomy for most injuries and more conservative surgical management for proximal ductal injuries involving the head of the pancreas. More recently, nonoperative management has been utilized, especially in the pediatric population, with the potential for increased rates of pseudocyst and pancreatic fistulae and the potential for the need for further intervention and increased hospital stay. This review presents recent data focusing on the diagnosis, management, and outcomes of blunt pancreatic injury.

Endothelial cells potentiate oxidant-mediated Kupffer cell phagocytic killing.

Phagocytosis and killing of circulating organisms by Kupffer cells (KCs) are discrete, important components of host defense. However, the killing mechanism(s) are not fully understood, and the potential role of adjacent nonparenchymal cells such as hepatic endothelial cells has not been defined. Rat KCs -/+ an hepatic endothelial cell enriched cellular fraction (HECEF) were incubated with Candida parapsilosis and assayed for phagocytosis and phagocytic killing by validated fluorochromatic vital staining. The role of reactive oxygen metabolites in KC phagocytic functions was examined by inhibition with superoxide dismutase and/or catalase. Diphenyleneiodonium and allopurinol were used to examine the potential roles of NADPH oxidase and xanthine oxidase, respectively, in generating these toxic oxidants. Coculture with HECEF increased KC phagocytic activity (from 75% to 88%) and candidacidal activity (from 20% to 31%). Superoxide dismutase, catalase, diphenyleneiodonium, or allopurinol caused inhibition of candidacidal activity, but did not affect phagocytosis, and did not block the potentiation of phagocytosis or of killing caused by coculture with HECEF. Reactive oxygen intermediates generated by both NADPH oxidase and xanthine oxidase-dependent pathways are important in KC killing of Candida parapsilosis. In vitro, KC phagocytosis and killing are potentiated (via a non-oxidant-mediated mechanism) by coculture with a preparation of hepatic non-parenchymal cells composed primarily of endothelial cells.

Inhibition of NF-kappaB by IkappaB prevents cytokine-induced NO production and promotes enterocyte apoptosis in vitro.

Nuclear factor-kappaB (N-kappaB) plays a key role in gut inflammation. NF-kappaB up-regulates proinflammatory genes encoding cytokines, adhesion molecules, and inducible nitric oxide synthase (iNOS). However, NF-kappaB has also been shown to up-regulate protective or anti-apoptotic factors. We utilized an adenoviral vector carrying a super-repressor form of the inhibitor of NF-kappaB, IkappaB, to examine the effects of NF-kappaB inhibition on cytokine-induced nitric oxide production and apoptosis in rat small intestinal epithelial cells (IEC-6). Chemical inhibitors of NF-kappaB, including pyrrolidine dithiocarbamate (PDTC), tosyl-lysine-chloromethylketone (TLCK), genistein, and N-acetyl-leu-leu-norleucinal (n-LLnL) were also utilized. Treatment of AdIkappaB-transfected cells with cytomix [1000 U/mL IFN-gamma, 1 nM IL-1beta, and 10 ng/mL tumor necrosis factor alpha (TNFalpha)] or TNFalpha-containing cytokine combinations resulted in inhibition of cytokine-induced nitrite production and a marked increase in apoptosis compared to control cells. Apoptosis occurred independently of nitric oxide (NO) production since exogenous sources of NO did not inhibit apoptosis. Inducible NOS and clAP were down-regulated in AdIkappaB-transfected cells treated with cytomix. TLCK and LLnL treatment also induced apoptosis in cytomix-treated cells, while PDTC and genistein did not. Thus, although NF-kappaB up-regulates various pro-inflammatory genes, it may also have protective or anti-apoptotic effects in enterocytes. NF-kappaB appears necessary for upregulating cIAP in IEC-6 cells upon cytokine exposure.

Development of a novel age-specific pediatric trauma score.

BACKGROUND/PURPOSE: Trauma scoring systems are needed to provide efficient triage of injured patients and to assess differences in outcomes and quality of care between different trauma centers. Current scoring systems used in pediatric trauma are not age specific, and thus have significant limitations. METHODS: The authors queried the Pennsylvania Trauma Outcome Study for all children 0 to 16 years entered in the database from 1993 to 1996. Age-specific threshold values for systolic blood pressure, pulse, and respiratory rate were established. Using coded scores for these age-specific values and Glasgow Coma Scale, an age-specific pediatric trauma score (ASPTS) was derived. Triage ASPTS (T-ASPTS) consisted of the integer sum of coded scores for the 4 variables, whereas ASPTS was calculated using weighted coefficients derived from logistic regression for each variable. RESULTS: T-ASPTS correlated with mortality rate. Using a threshold score of less than 10, T-ASPTS predicted mortality rate with a sensitivity of 96.97% and a specificity of 88.83%. T-ASPTS predicted mortality rate and percentage of patients with Injury Severity Score greater than 20 with similar sensitivity to the Revised Trauma Score (RTS), but T-ASPTS was more specific. The ASPTS predicted probability of survival more accurately than the RTS. CONCLUSIONS: ASPTS performs favorably as both a triage score and as a tool for predicting probability of survival for outcomes analysis. Further comparisons to existing trauma scores are needed to verify the utility of ASPTS.

Improved functional outcome for severely injured children treated at pediatric trauma centers.

BACKGROUND: Controversy exists regarding the impact of pediatric trauma centers (PTC) on survival for injured children. However, functional outcome for children treated at PTC compared with adult trauma centers (ATC) has not been evaluated. METHODS: An analysis of children entered in the Pennsylvania Trauma Outcome Study between 1993 and 1997 was conducted. Patients were stratified according to type of trauma center: PTC; Level I ATC; Level II ATC; or ATC with added qualifications (AQ). Functional outcome at discharge was analyzed. RESULTS: For severely injured children, there was an overall trend toward improved functional outcome at PTC compared with ATC AQ and ATC I, but no difference compared with ATC II. PTC showed improved functional outcome at discharge for head injury compared with ATC AQ and ATC I. CONCLUSION: There is an overall trend toward improved functional outcome at discharge for children treated at PTC compared with those treated at ATC AQ and ATC I. Improved outcome for head injury may be a key factor contributing to improved outcome at PTC.

Salmonella typhimurium induces apoptosis in human monocyte-derived macrophages.

Salmonella species represent a leading cause of gastroenteritis worldwide. More recently, they have been proposed as putative vaccine delivery vehicles in humans. Oral infection with Salmonella leads to invasion of the intestinal epithelial barrier and subsequent interaction with mucosal macrophages. In this study, we investigated the fate of Salmonella typhimurium-infected human macrophages differentiated from blood monocytes by GM-CSF. Wild type S. typhimurium strain SL1344 induced macrophage surface blebbing and caused the release of host cytoplasmic lactate dehydrogenase beginning 30 min post-infection. Three hours later more than 80% of the macrophages in the culture were killed. In contrast, during the same period, macrophages infected with the non-invasive S. typhimurium strain BJ66 remained viable. Chromatin fragmentation is a hallmark of cells undergoing apoptosis. Using TUNEL analysis, we observed chromatin fragmentation in macrophages infected with SL1344 but not in BJ66 infected cells. Consistent with this observation, we found that pretreatment of human macrophages with an inhibitor of caspase-3, a member of the pro-apoptotic enzyme family shown to be involved in S. typhimurium-induced killing of mouse macrophages, reduced SL1344-mediated cytotoxicity by 40%. Our study provides the first evidence that invasive S. typhimurium induces apoptosis in human macrophages that were differentiated from blood monocytes by GM-CSF, and that cell death is a caspase-dependent phenomenon.

Impact of pediatric trauma centers on mortality in a statewide system.

BACKGROUND: Regional pediatric trauma centers (PTC) were established to optimize the care of injured children. However, because of the relative shortage of PTC, many injured children continue to be treated at adult trauma centers (ATC). As a result, a growing controversy has evolved regarding the impact of PTC and ATC on outcome for injured children. METHODS: A retrospective analysis of 13,351 injured children entered in the Pennsylvania Trauma Outcome Study between 1993 and 1997 was conducted. Patients were stratified according to mechanism of injury, injury severity, specific organ injury, and type of trauma center: PTC; Level I ATC (ATC I); Level II ATC (ATC II); or ATC with added qualifications to treat children (ATC AQ). Mortality was the major outcome variable measured. RESULTS: Most injured children were treated at a PTC or ATC AQ. The majority of children below 10 years of age were admitted to PTC. Patients treated at PTC and ATC had similar injury severity as determined by median Injury Severity Score, mean Revised Trauma Score, and Glasgow Coma Scale. Overall survival was significantly better at PTC and ATC AQ compared with ATC I and ATC II. Survival for head, spleen, and liver injuries was significantly better at PTC compared with ATC AQ, ATC I, or ATC II. Children who sustained moderate or severe head injuries were more likely to undergo neurosurgical intervention and have a better outcome when treated at a PTC. Despite similar mean Abbreviated Injury Scores for spleen and liver, significantly more children underwent surgical exploration (especially splenectomy) for spleen and liver injuries at ATC compared with PTC. CONCLUSION: Children treated at PTC or ATC AQ have significantly better outcome compared with those treated at ATC. Severely injured children (Injury Severity Score > 15) with head, spleen, or liver injuries had the best overall outcome when treated at PTC. This difference in outcome may be attributable to the approach to operative and nonoperative management of head, liver, and spleen injuries at PTC.