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1.
J Trauma Acute Care Surg ; 80(2): 229-36, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26502211

ABSTRACT

BACKGROUND: Surgical site infections (SSIs) are important sources of morbidity, prolonged hospital stays, and readmissions, so they have become a major economic burden. We hypothesized that surgical wound assessment by sonography (SWATS) used at the bedside would detect wound fluid collections and that the presence of such collections would predict SSI better than standard clinical examination. If so, SWATS might be used to indicate early intervention that could prevent SSI morbidity. METHODS: A prospective, single-institution observational study was conducted on adult inpatients following open abdominal surgery for trauma, gastrointestinal pathology, or biliary pathology at high risk (>5%) for SSI using traditional wound classifications. After informed consent was obtained, SWATS was performed using a smartphone-based ultrasound system on postoperative Day 2 to 4 and again before discharge or at postoperative Day 30, whichever came first. Primary treating physicians delivered standard wound care and were blinded to SWATS. SSI was diagnosed if treatment was implemented for suspected or documented wound infection by the treating physician. Results were analyzed by χ test and two-sample pooled variance t test where appropriate, with significance set at p < 0.05. RESULTS: Forty-nine patients were studied. Nineteen patients had peri-incisional fluid collections found by SWATS. Eight of these patients went on to develop an SSI. SSI was significantly associated with the presence of fluid collections on SWATS (p = 0.009). SWATS had a sensitivity of 72.7% (0.43-0.92), a specificity of 71.1% (0.62-0.77), a positive predictive value of 42.1% (0.25-0.53), and a negative predictive value of 90.0% (0.79-0.97). CONCLUSION: SWATS has a high negative predictive value that may allow it be an effective screening tool for developing SSI in high-risk surgical wounds. SWATS has the potential to be a useful and cost-effective adjunct to the clinician by objectively suggesting need for early therapy. Further study with larger sample sizes and randomized, SWATS-based interventions are required to validate this small study and determine its place in clinical care. LEVEL OF EVIDENCE: Diagnostic study, level IV.


Subject(s)
Abdomen/surgery , Point-of-Care Systems , Surgical Wound Infection/diagnostic imaging , Abdominal Wound Closure Techniques , Adult , Aged , Aged, 80 and over , Female , Fluid Shifts , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Smartphone , Surgical Wound Infection/etiology , Ultrasonography
2.
Pediatr Dermatol ; 32(6): 808-12, 2015.
Article in English | MEDLINE | ID: mdl-26223454

ABSTRACT

OBJECTIVES: Hepatic hemangiomas are often found in association with multiple cutaneous infantile hemangiomas. Screening abdominal ultrasonography has been recommended for patients with five or more cutaneous lesions. We sought to determine whether hemangiomas found through screening had improved clinical outcomes. METHODS: Patients entered into our hepatic hemangioma registry between 1995 and 2012 were reviewed. RESULTS: Seventy-two patients with multiple cutaneous and hepatic hemangiomas were identified; 43 (60%) were detected through screening. The median age at diagnosis was 41 days for screened patients and 53 days for those not screened. Screening detected 40 (93%) multifocal and 3 (7%) diffuse hemangiomas, compared to 18 (62%) and 11 (38%), respectively, in the nonscreened group. Patients identified by screening had lower incidences of congestive heart failure and hypothyroidism and were less likely to receive treatment for their hemangiomas. The mortality rate in the children not screened was 28% (n = 8). None of the patients found by screening died (p < 0.001). Multivariate analysis of treated patients demonstrated that screening was a significant predictor of reduced mortality (p = 0.04). CONCLUSION: Hepatic hemangiomas found through screening ultrasonography are less likely to develop serious clinical sequelae. Although the reasons for this may include detection of hemangiomas that are less likely to progress to symptomatic disease, it appears that it also allows for earlier intervention for more concerning (e.g. diffuse) subtypes. Screening may allow for closer surveillance and earlier treatment before life-threatening progression in a subset of infants with liver hemangiomas, preventing complications and reducing mortality.


Subject(s)
Hemangioma, Capillary/epidemiology , Hemangioma/epidemiology , Liver Neoplasms/epidemiology , Neonatal Screening/methods , Registries , Skin Neoplasms/epidemiology , Cohort Studies , Comorbidity , Female , Follow-Up Studies , Hemangioma/diagnosis , Hemangioma, Capillary/congenital , Hemangioma, Capillary/diagnosis , Hospitals, Pediatric , Humans , Incidence , Infant , Infant, Newborn , Liver Neoplasms/diagnosis , Male , Monitoring, Physiologic , Multivariate Analysis , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Severity of Illness Index , Skin Neoplasms/diagnosis , Survival Rate
3.
J Pediatr Surg ; 50(5): 837-41, 2015 May.
Article in English | MEDLINE | ID: mdl-25783331

ABSTRACT

PURPOSE: Multifocal and diffuse hepatic hemangiomas are true infantile hemangiomas, which likely exist in a continuum. We reviewed our hepatic hemangioma registry to identify prognostic indicators for mortality. METHODS: Registry records entered between 1995 and 2012 were reviewed. Clinical characteristics were evaluated for prognostic significance using the multivariable Cox proportional hazards model. Survival data were analyzed using the Kaplan-Meier product-limit method. RESULTS: We identified 123 patients with multifocal (n=91) and diffuse (n=32) hepatic hemangiomas. Mortality was 16% (n=20); 40% (n=8) had multifocal and 60% (n=12) had diffuse lesions. A diagnosis of diffuse disease (hazard ratio: 9.9, 95% CI: 2.0-50.8, P=.002) and congestive heart failure (CHF) (hazard ratio: 3.9, 95% CI: 1.3-14.2, P=.031) were significant risk factors for mortality across the continuum; age at presentation, cardiomegaly, presence of shunts, and hypothyroidism were not statistically significant independent risk factors. Among patients with diffuse lesions, eight (67%) who died had abdominal compartment syndrome, which was also associated with mortality (P=.002). CONCLUSIONS: Hepatic hemangioma patients with CHF or diffuse disease are at higher risk for mortality. Patients with multifocal lesions without CHF may go undetected until lesions become diffuse. Aggressive treatment of symptomatic patients and close follow-up of asymptomatic patients may improve mortality.


Subject(s)
Hemangioma/epidemiology , Liver Neoplasms/epidemiology , Registries , Risk Assessment , Aged , Female , Hemangioma/diagnosis , Humans , Infant , Infant, Newborn , Kaplan-Meier Estimate , Liver Neoplasms/diagnosis , Male , Massachusetts/epidemiology , Middle Aged , Neoplasm Staging , Risk Factors , Survival Rate/trends
4.
J Pediatr ; 166(4): 1048-54.e1-5, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25681199

ABSTRACT

OBJECTIVES: To test the hypothesis that somatic phosphatidylinositol-4,5-bisphospate 3-kinase, catalytic subunit alpha (PIK3CA) mutations would be found in patients with more common disorders including isolated lymphatic malformation (LM) and Klippel-Trenaunay syndrome (KTS). STUDY DESIGN: We used next generation sequencing, droplet digital polymerase chain reaction, and single molecule molecular inversion probes to search for somatic PIK3CA mutations in affected tissue from patients seen at Boston Children's Hospital who had an isolated LM (n = 17), KTS (n = 21), fibro-adipose vascular anomaly (n = 8), or congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (n = 33), the disorder for which we first identified somatic PIK3CA mutations. We also screened 5 of the more common PIK3CA mutations in a second cohort of patients with LM (n = 31) from Seattle Children's Hospital. RESULTS: Most individuals from Boston Children's Hospital who had isolated LM (16/17) or LM as part of a syndrome, such as KTS (19/21), fibro-adipose vascular anomaly (5/8), and congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (31/33) were somatic mosaic for PIK3CA mutations, with 5 specific PIK3CA mutations accounting for ∼ 80% of cases. Seventy-four percent of patients with LM from Seattle Children's Hospital also were somatic mosaic for 1 of 5 specific PIK3CA mutations. Many affected tissue specimens from both cohorts contained fewer than 10% mutant cells. CONCLUSIONS: Somatic PIK3CA mutations are the most common cause of isolated LMs and disorders in which LM is a component feature. Five PIK3CA mutations account for most cases. The search for causal mutations requires sampling of affected tissues and techniques that are capable of detecting low-level somatic mosaicism because the abundance of mutant cells in a malformed tissue can be low.


Subject(s)
Abnormalities, Multiple , DNA/genetics , Klippel-Trenaunay-Weber Syndrome/genetics , Lymphatic Abnormalities/genetics , Mutation , Phosphatidylinositol 3-Kinases/genetics , Vascular Malformations/genetics , Child , Child, Preschool , Class I Phosphatidylinositol 3-Kinases , Female , High-Throughput Nucleotide Sequencing , Humans , Infant , Klippel-Trenaunay-Weber Syndrome/diagnosis , Klippel-Trenaunay-Weber Syndrome/metabolism , Lymphatic Abnormalities/diagnosis , Lymphatic Abnormalities/metabolism , Male , Phosphatidylinositol 3-Kinases/metabolism , Polymerase Chain Reaction , Vascular Malformations/diagnosis , Vascular Malformations/metabolism
5.
J Virol ; 82(16): 7758-67, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18524831

ABSTRACT

The human immunodeficiency virus type 1 (HIV-1) Nef protein upregulates the expression of the invariant chain (Ii)/major histocompatibility complex class II (MHC-II) complex at the cell surface. This complex appears to reach the antigen-loading endosomal compartment at least in part via an indirect pathway in which it is internalized from the cell surface via the adaptor protein 2 (AP-2) complex. Here we provide evidence for a competition model to explain how Nef upregulates the expression of Ii at the cell surface. In this model, Nef and Ii compete for binding to AP-2. In support of this model, Nef decreased the rate of internalization of Ii from the cell surface. The AP-binding dileucine motif in Nef, ENTSLL(165), was necessary and sufficient for the upregulation of Ii. In addition, two leucine-based AP-binding motifs in the Ii cytoplasmic tail, DDQRDLI(8) and EQLPML(17), were critical for the efficient upregulation of Ii by Nef. Experiments using Nef variants in which the native dileucine-based sorting motif was replaced with similar motifs from cellular transmembrane proteins allowed modulation of AP-binding specificity. Analysis of these variants suggested that the binding of Nef to AP-2 is sufficient to upregulate Ii at the plasma membrane. Finally, interference with the expression of AP-2 caused an upregulation of Ii at the plasma membrane, and this decreased the effect of Nef. These data indicate that Nef usurps AP-2 complexes to dysregulate Ii trafficking and potentially interfere with antigen presentation in the context of MHC-II.


Subject(s)
Gene Expression Regulation, Viral , Gene Products, nef/biosynthesis , Gene Products, nef/physiology , Histocompatibility Antigens Class II/physiology , Adaptor Protein Complex 2/metabolism , Amino Acid Motifs , Antigen Presentation , Binding, Competitive , CD4-Positive T-Lymphocytes/metabolism , Cell Membrane/metabolism , Cytoplasm/metabolism , HeLa Cells , Histocompatibility Antigens Class II/chemistry , Humans , Leucine/chemistry , Leukocytes, Mononuclear/metabolism , Models, Biological
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