Parkes Weber syndrome associated with two somatic pathogenic variants in RASA1.

Parkes Weber syndrome is associated with autosomal dominant inheritance, caused by germline heterozygous inactivating changes in the RASA1 gene, characterized by multiple micro arteriovenous fistulas and segmental overgrowth of soft tissue and skeletal components. The focal nature and variable expressivity associated with this disease has led to the hypothesis that somatic "second hit" inactivating changes in RASA1 are necessary for disease development. We report a 2-yr-old male with extensive capillary malformation and segmental overgrowth of his lower left extremity. Ultrasound showed subcutaneous phlebectasia draining the capillary malformation; magnetic resonance imaging showed overgrowth of the extremity with prominence of fatty tissues, fatty infiltration, and enlargement of all the major muscle groups. Germline RASA1 testing was normal. Later somatic testing from affected tissue showed two pathogenic variants in RASA1 consistent with the c.934_938del, p.(Glu312Argfs*14) and the c.2925del, p.(Asn976Metfs*20) with variant allele fractions of 3.6% and 4.2%, respectively. The intrafamilial variability of Parkes Weber syndrome involving segmental overgrowth of soft tissue, endothelium, and bone is strongly suggestive of a somatic second-hit model. There are at least two reports of confirmed second somatic hits in RASA1 To our knowledge, this is the first report of an individual with two somatic pathogenic variants in the RASA1 gene in DNA from a vascular lesion.

The Cost-Effectiveness of Platelet-Rich Plasma Compared With Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis.

PURPOSE: To examine the cost-effectiveness of a series (total of 3 injections) of intra-articular platelet-rich plasma (PRP) injections in comparison to that of hyaluronic acid (HA) viscosupplementation for the treatment of symptomatic knee osteoarthritis. METHODS: Outcome data regarding the use of PRP or HA injections for the treatment of symptomatic knee osteoarthritis were determined from the highest-quality data (Level I) available in the literature until 2015. Health utility values were then derived from these high-quality data. Costs were determined by examining typical charges for patients undergoing a series of either PRP or HA injections for the treatment of this condition at a large private orthopaedic practice. These health utility values and costs were used to create an expected-value decision analysis model. RESULTS: The results of the model revealed that the cost per quality-adjusted life-year (QALY) of a series of PRP injections was $8,635.23/QALY and that of a series of HA injections was $5,331.75/QALY. A series of PRP injections was associated with a higher initial cost than a series of HA injections (difference, $1,433.67); however, PRP was also more effective (higher utility value) than HA by 0.11 QALYs (0.69 vs 0.58, P = .0062) at 1 year. The incremental cost-effectiveness ratio of the use of PRP injections as opposed to HA was $12,628.15/QALY. CONCLUSIONS: Although a series of either PRP ($8,635.23/QALY) or HA ($5,331.75/QALY) injections for the treatment of symptomatic knee osteoarthritis would be considered cost-effective (cost per QALY < $50,000), PRP injections were not more cost-effective than HA injections. However, PRP was significantly more effective at 1 year, and being associated with an incremental cost-effectiveness ratio of $12,628.15/QALY when compared with HA, a series of PRP injections should be considered a reasonable and acceptable alternative to HA injections for the treatment of symptomatic knee osteoarthritis. LEVEL OF EVIDENCE: Level II, economic and decision analysis of Level I studies.

A usability and safety analysis of electronic health records: a multi-center study.

To characterize the variability in usability and safety of EHRs from two vendors across four healthcare systems (2 Epic and 2 Cerner). Twelve to 15 emergency medicine physicians participated from each site and completed six clinical scenarios. Keystroke, mouse click, and video data were collected. From the six scenarios, two diagnostic imaging, laboratory, and medication tasks were analyzed. There was wide variability in task completion time, clicks, and error rates. For certain tasks, there were an average of a nine-fold difference in time and eight-fold difference in clicks. Error rates varied by task (X-ray 16.7% to 25%, MRI: 0 to 10%, Lactate: 0% to 14.3%, Tylenol: 0 to 30%; Taper: 16.7% to 50%). The variability in time, clicks, and error rates highlights the need for improved implementation optimization. EHR implementation, in addition to vendor design and development, is critical to usable and safe products.

Assessment of Nursing Response to a Real-Time Alerting Tool for Sepsis: A Provider Survey.

Background: An information technology solution to provide a real-time alert to the nursing staff is necessary to assist in identifying patients who may have sepsis and avoid the devastating effects of its late recognition. The objective of this study is to evaluate the perception and adoption of sepsis clinical decision support. Methods: A cross-sectional survey over a three-week period in 2015 was conducted in a major tertiary care facility. A sepsis alert was launched into five pilot units (including: surgery, medical-ICU, step-down, general medicine, and oncology). The pilot unit providers consisted of nurses from five inpatient units. Frequency, summary statistics, Chi-square, and nonparametric Kendall tests were used to determine the significance of the association and correlation between six evaluation domains. Results: A total of 151 nurses responded (53% response rate). Questions included in the survey addressed the following domains: usability, accuracy, impact on workload, improved performance, provider preference, and physician response. The level of agreeability regarding physician response was significantly different between units (p=0.0136). There were significant differences for improved performance (p=0.0068) and physician response (p=0.0503) across levels of exposure to the alert. The strongest correlations were between questions related to usability and the domains of: accuracy (τ=0.64), performance (τ=0.66), and provider preference (τ=0.62), as well as, between the domains of: provider performance and provider preference (τ=0.67). Discussion: Performance and preference of providers were evaluated to identify strengths and weaknesses of the sepsis alert. Effective presentation of the alert, including how and what is displayed, may offer better cognitive support in identifying and treating septic patients.

Autologous chondrocyte implantation in the patella: a multicenter experience.

BACKGROUND: Cartilage defects in the patella are common, and a subset of patients does not respond to nonoperative measures. While most cartilage repair techniques have demonstrated good outcomes in the femoral condyles, the patellofemoral compartment poses special challenges. HYPOTHESIS: Repair of patellar cartilage defects with autologous chondrocyte implantation (ACI) will provide lasting improvements in pain and function. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients were treated at 1 of 4 participating cartilage repair centers with ACI for cartilage defects in the patella; bipolar (patella + trochlea) defects were included as well. All patients were followed prospectively for at least 4 years with multiple patient-reported outcome instruments, including the International Knee Documentation Committee, Short Form-12, modified Cincinnati Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Knee Society scores. Treatment failure was defined as structural failure of the graft combined with pain requiring revision surgery. RESULTS: A total of 110 patients were available for analysis. As a group, they experienced both statistically significant and clinically important improvements in pain and function in all physical outcome scales. The International Knee Documentation Committee improved from 40 ± 14 preoperatively to 69 ± 20 at the last follow-up; the Cincinnati Rating Scale, from 3.2 ± 1.2 to 6.2 ± 1.8; and the Western Ontario and McMaster Universities Osteoarthritis Index, from 50 ± 22 to 29 ± 22 (all P < .0001). Ninety-two percent of patients stated that they would choose to undergo ACI again, and 86% rated their knees as good or excellent at the time of final follow-up. Nine patients (8%) were considered treatment failures, and 16% reported that their knees were not improved. CONCLUSION: Cartilage repair in the patellofemoral joint is arguably not without its challenges. Autologous chondrocyte implantation remains off-label in the patella, a fact that needs to be discussed with prospective patients during the informed consent process. However, when performed with attention to patellofemoral biomechanics, self-rated subjective good and excellent outcomes can be achieved in more than 80% of patients treated with ACI, even in a patient population with large and frequently bipolar defects such as the one presented in this study. However, final functional scores, although significantly improved, still reflected residual disability in this challenging group of patients.

Autologous chondrocyte implantation and anteromedialization for isolated patellar articular cartilage lesions: 5- to 11-year follow-up.

BACKGROUND: Isolated chondral lesions of the patella are particularly challenging to treat, and long-term studies of treated isolated patellar lesions are limited. Previous short-term studies have reported favorable outcomes of autologous chondrocyte implantation (ACI) of the patella and/or trochlea, with a trend toward improvement when anteromedialization (AMZ) of the tibial tubercle was performed with the procedure. HYPOTHESIS: Autologous chondrocyte implantation with concomitant AMZ for symptomatic isolated patellar lesions provides functional and symptomatic improvement in patients at a minimum 5-year follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with failed primary treatment of isolated patellar full-thickness articular cartilage defects and patellofemoral malalignment who were treated with ACI and AMZ of the tibial tubercle at least 5 years prior were contacted for final postoperative outcome scores. Outcome scales including the International Knee Documentation Committee (IKDC), Lysholm, modified Cincinnati Knee Rating System, and 12-item Short Form Health Survey (SF-12) scores were assessed at baseline and final follow-up. RESULTS: Of 27 eligible patients, 23 (25 knees) were available for assessment at a mean follow-up of 7.6 years (range, 5.1-11.4 years). Significant improvements from baseline to final follow-up were observed in the IKDC score (from 42.5 to 75.7; P < .0001), modified Cincinnati Knee Rating System score (from 3.0 to 7.0; P < .0001), Lysholm score (from 40.2 to 79.3; P < .0001), and SF-12 score (physical component score: from 41.2 to 47.6; P = .002; mental component score: from 48.1 to 60.7; P = .0001). Most patients (83%; 19/23) rated their surgery as good or excellent. The overall reoperation rate was 40% (10/25) largely because of periosteal hypertrophy (33%). One patient failed at 5.9 years postoperatively and underwent patellofemoral arthroplasty. CONCLUSION: Combined ACI and AMZ resulted in significant improvements in symptoms and function with a low incidence of adverse events in patients with isolated symptomatic patellar chondral defects after a mean follow-up of more than 7 years.

A benefit-risk analysis of natalizumab in the treatment of patients with multiple sclerosis when considering the risk of progressive multifocal leukoencephalopathy.

BACKGROUND: Natalizumab is a highly effective treatment for patients with relapsing-remitting multiple sclerosis (RRMS). Treatment with natalizumab has been associated with progressive multifocal leukoencephalopathy (PML), a rare yet serious disease of the brain. Published studies have quantified the PML risk by the presence of anti-JC virus antibodies, previous immunosuppressant use, and duration of natalizumab treatment. OBJECTIVES: The aim of this analysis was to evaluate the net benefits and risks for patients with RRMS receiving natalizumab treatment compared with fingolimod, interferon-ß, and no treatment across PML risk sub-groups. RESEARCH DESIGN AND METHODS: Based on previously validated MS model structures, a Markov cohort model was developed to assess the impact of treatment on quality-adjusted life years (QALYs). Natalizumab-treated patients were classified by PML risk sub-groups and analysed separately for short-term (2 years) and long-term (20 years) time horizons. MAIN OUTCOME MEASURES: Main outcome measures included total QALYs by PML risk sub-group and the increase in PML risk associated with natalizumab treatment which offsets the quality of life benefit of comparator treatments. RESULTS: Results showed higher QALYs with natalizumab versus all other comparators across PML risk sub-groups over both time horizons. For the QALYs of natalizumab to equal the QALYs of fingolimod, interferon-ß, and no treatment, the risk of PML would have to increase 4.6-84.2 times, 24.0-444.3 times, and 5.7-106.1 times, respectively (short term), and 1.4-123.4 times, 1.5-138.3 times, and 2.2-193.7 times, respectively (long term). CONCLUSION: This study shows that natalizumab generates the most net health benefits in terms of quality-adjusted life years compared with fingolimod, interferon-ß, or no treatment, even when the risk of natalizumab-associated PML is taken into consideration. This study is limited by the availability of published data around natalizumab-associated PML, as well as the constraints of the model used to conduct the analysis.

Factors associated with treatment failure in vertebral osteomyelitis requiring spinal instrumentation.

Patients with vertebral osteomyelitis may require instrumentation for spinal stabilization. Determining the optimal duration and type of antimicrobial therapy for these patients is challenging. The aim of this study was to examine risk factors for treatment failure, in particular antimicrobial duration, in a cohort of patients requiring spinal instrumentation for vertebral osteomyelitis. We conducted a retrospective cohort study of all patients with vertebral osteomyelitis who had spinal instrumentation between January 2002 and January 2012 at the University of Maryland Medical Center. The primary outcome measure was treatment failure >4 weeks postoperatively. We identified 131 patients with vertebral osteomyelitis requiring spinal instrumentation, 94 of whom had >4 weeks of follow-up and were included in the primary analysis. Treatment failure occurred in 22 of the 94 patients (23%) at a median of 4 months after surgery. Among patients who failed therapy, 20 of 22 failed within 1 year of surgery. Cervical and thoracic infection sites and the presence of negative cultures were associated with fewer treatment failures. Addition of rifampin and the use of chronic suppressive antimicrobials did not affect treatment failure rate. Twenty-three percent of patients with spinal instrumentation for vertebral osteomyelitis experienced treatment failure. Treatment failure almost always occurred within the first year of spinal instrumentation.

Sclerotherapy for intra-abdominal lymphatic malformations in children.

PURPOSE: Sclerotherapy is well described as a treatment for lymphatic malformations (LMs) in the head, neck, and other soft tissue areas. This study aims to evaluate the effectiveness of intralesional sclerotherapy as primary treatment for intra-abdominal LMs in children. METHODS: We conducted a retrospective review from 2008 to 2012 of all children with intra-abdominal LMs treated with sclerotherapy at our tertiary children's hospital. RESULTS: In this study, five patients underwent sclerotherapy as a primary intervention for intra-abdominal LMs. The ages of these patients ranged from 12 to 52 months at the time of initial treatment. Doxycycline was used as the primary sclerotherapy agent. The patients required between three and five (median 3) sclerosing treatments over a period that ranged from 5 to 366 days (median 28). No child has required an operation and all LMs have decreased in size. The median decease in maximum diameter is 62% (21-67). Complete resolution has not been attained but all have experienced symptomatic relief with a median follow-up of 3 (1-24) months. CONCLUSIONS: Sclerotherapy is an effective first-line therapy for intra-abdominal LMs in the pediatric population and should be considered when treating these difficult lesions.

The association of near infrared spectroscopy-derived StO2 measurements and biomarkers of endothelial activation in sepsis.

Near infrared spectroscopy (NIRS) may be utilized in conjunction with a vascular occlusion test to quantify a tissue bed's ability to re-oxygenate by measuring continuous tissue oxygen saturation recovery rate. We hypothesize that NIRS recovery slope will be associated with expression of endothelial biomarkers, thus, making it a feasible bedside surrogate for assessing endothelial activation/dysfunction in patients with sepsis. A secondary analysis of a prospective, multicenter, observational study was done on a convenience sample of adult patients at four university emergency departments consisting of patients with septic shock, sepsis without shock and patients without infection. At enrollment we measured the NIRS-derived measurements and collected plasma to assay biomarkers of endothelial activation. 186 patients were enrolled in the study. The mean age was 63 (± 16) years with 60 % male gender. Univariate analysis assessing the linear relationship between the recovery slope with endothelial biomarkers, found a weak but statistical significant association between NIRS recovery slope and soluble fms-like tyrosine kinase-1 (sFLT-1) and tPAI-1 (r = -0.08, p < 0.0001 and r = -0.06, p = 0.002). When adjusting for diabetes, age and sequential organ failure assessment score at enrollment, only sFLT-1 persisted having a statistically significant association (r = -0.04, p = 0.01). We found a weak, but statistically significant relationship between NIRS-derived measurements and biomarkers of endothelial activation/dysfunction in patients with sepsis. This study fails to support the use of NIRS-derived measurements as a clinical or research tool to identify patients with endothelial cell activation/dysfunction and informs researchers that this is not a robust option for identifying this lesion at the bedside.

Biomarkers of endothelial cell activation in early sepsis.

PURPOSE: The objective of this study was to investigate the association of endothelial-related markers with organ dysfunction and in-hospital mortality to validate our earlier findings in a multicenter study. We hypothesize that (i) endothelial biomarkers will be associated with organ dysfunction and mortality in sepsis and that (ii) soluble fms-like tyrosine kinase 1 (sFlt-1) holds promise as a novel prognostic marker in sepsis. METHODS: This was a prospective, multicenter, observational study of a convenience sample of emergency department (ED) patients with a suspected infection presenting to one of four urban, academic medical center EDs between January 2009 and January 2010. We collected plasma while the patients were in the ED and subsequently assayed endothelial-related biomarkers, namely, sFlt-1, soluble E-selectin, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and plasminogen activator inhibitor 1 (PAI-1). Outcomes were organ dysfunction and in-hospital mortality. RESULTS: We enrolled a total of 166 patients: 63 with sepsis (38%), 61 with severe sepsis (37%), and 42 with septic shock (25%). All endothelial biomarkers were significantly associated with sepsis severity, P < 0.002. We found a significant intercorrelation between all biomarkers, strongest between sFlt-1 and PAI-1 (r = 0.61, P < 0.001) and PAI-1 and soluble E-selectin and soluble intercellular adhesion molecule 1 (r = 0.49, P < 0.001). Among the endothelial biomarkers, sFlt-1 had the strongest association with Sequential Organ Failure Assessment score (r = 0.58, P < 0.001). Soluble fms-like tyrosine kinase 1 and PAI-1 had the highest area under the operating receiver characteristic curve for mortality of 0.87. CONCLUSIONS: This multicenter validation study confirms that markers of endothelial activation are associated with sepsis severity, organ dysfunction, and mortality in sepsis. This supports the hypothesis that the endothelium plays a central role in the pathophysiology of sepsis and may serve as a more accurate prediction tool and a target for therapies aimed at ameliorating endothelial cell dysfunction. In addition, sFLT-1 holds promise as a novel sepsis severity biomarker.

Embolization of a bleeding Dieulafoy lesion of the duodenum in a child. Case report and review of the literature.

We report an adolescent with chronic, recurrent upper gastrointestinal bleeding in whom extensive prior investigations failed to reveal the source of bleeding. Angiography accurately identified a bleeding Dieulafoy lesion of the duodenum which was successfully embolized. The clinical history, angiographic appearances and treatment of this rare lesion are presented.

Single center experience of a vancomycin resistant enterococcal endocarditis cohort.

OBJECTIVES: Vancomycin resistant enterococcus (VRE) infective endocarditis (IE) is an increasing nosocomial problem. We describe the clinical management and outcomes of a cohort of patients with VRE IE at a tertiary endocarditis referral center. METHODS: Retrospective review of all proven cases of VRE IE, from July 2000 through January 2008 was performed. Demographics, comorbidities and therapeutic details were collected and analyzed to assess for risk factors and clinical outcomes. RESULTS: Fifty cases of VRE IE were identified: 26 (52%) were Enterococcus faecium and 24 were Enterococcus faecalis. Vancomycin resistant E. faecalis IE was associated with the presence of a central venous line, liver transplantation, and mitral valve infection while VR E. faecium IE was significantly associated with tricuspid valve infection (p=0.03). The median duration of bacteremia was 14 days for E. faecium and 4 days for E. faecalis, respectively (p=0.002). Factors associated with mortality on bivariate analysis were hemodialysis via a catheter with VR E. faecium (OR=11.7. CI 1.1-122, p=0.02) and liver transplantation with both species. Combination antimicrobial therapy (OR=0.5 CI=0.06-3.2, p=0.1) and valve surgery (OR 1.3 CI 0.8-20, p=0.02) trended toward improved survival with E. faecalis on bivariate analysis. On multivariate analysis, none of the associations were significant. CONCLUSIONS: Hemodialysis and liver transplantation were factors associated with acquisition of VRE IE. There was a higher mortality and prolonged bacteremia with VR E. faecium IE than VR E. faecalis IE. Although not significant, combination antimicrobial therapy and surgical intervention trended toward improved survival.

Bone presence between the central peg's radial fins of a partially cemented pegged all poly glenoid component suggest few radiolucencies.

BACKGROUND: Cement penetration problems and/or cement-induced bone necrosis may contribute to glenoid component failures. An all polyethylene component was developed that promotes biologic fixation between radial fins of its central peg and utilizes minimal cement fixation for its peripheral pegs, but it has little published data. We hypothesized better bone presence between the radial fins would be associated with less overall radiolucencies. This study's purpose was to utilize computed tomography (CT) and plain films to assess for bone between the central peg's radial fins and to assess overall component radiolucencies. MATERIALS AND METHODS: Thirty-five of 48 consecutively performed total shoulder arthroplasties (TSA) for primary glenohumeral osteoarthritis were in patients able to participate a minimum 2 years after surgery. All had reamed humeral head bone packed between radial fins of the central peg and minimal cement for the peripheral pegs. Thin cut (0.625 mm) CT scans, standardized plain films, Simple Shoulder Tests (SST), and Constant scores were obtained. A musculoskeletal radiologist calculated Yian CT scores, bone presence between fins on CT, and Lazarus radiolucency scores. RESULTS: At a mean of 43 months, by CT: 1) better Yian scores correlated with more bone between fins, and 2) bone was present in 6/6 inter-fin compartments in 23/35 shoulders, averaging 4.5/6 overall. Mean Lazarus radiolucency score was 0.45. Mean SST and Constant scores were 10.3 and 81.3, respectively. CONCLUSION: TSA utilizing autologous bone in inter-fin compartments of the central peg and minimal peripheral peg cement maintained bone presence a minimum 2 years post-op. More bone imparted fewer overall component radiolucencies.

Diagnostic imaging of vascular anomalies.

Medical imaging has become critically important in the diagnosis and treatment planning of vascular anomalies. The classification of lesions into fast-flow and slow-flow categories, the identification of a soft tissue mass, and the determination of the extent of the lesions are all facilitated by the use of magnetic resonance imaging, ultrasonography, catheter angiography, and other imaging studies. The use of these imaging techniques in the diagnosis and assessment of vascular tumors, malformations, and combined malformation syndromes is discussed in this article.

Continuous cardiac index monitoring: A prospective observational study of agreement between a pulmonary artery catheter and a calibrated minimally invasive technique.

INTRODUCTION: Continuous cardiac index (CCI) monitoring can provide information to assist in hemodynamic support. However, pulmonary artery catheters (PAC) pose logistic challenges in acute care settings. We hypothesized that CCI measured with a calibrated minimally invasive technique (LiDCO/PulseCO, UK) would have good agreement with the PAC. METHODS: We performed a prospective observational study in post-operative cardiac surgery patients. All patients had a PAC with CCI monitoring capability. We connected the LiDCO apparatus to a radial artery line and performed a one-time calibration with a lithium dilution indicator. In order to test the least invasive method possible, we used a peripheral intravenous (IV) line for indicator delivery rather than the conventional central line technique. We recorded paired PAC/LiDCO-PulseCO CCI measurements every minute for 3h. We blinded investigators and clinicians to minimally invasive data with an opaque shield over the monitor. We assessed agreement with Bland-Altman analysis. RESULTS: We obtained 1485 paired measurements in 8 subjects. The mean CI was 2.9L/min/m(2). By Bland-Altman plot, PAC and LiDCO measurements showed minimal bias (-0.01), but the 95% limits of agreement (+/-2SD) of+/-1.3L/min/m(2) were relatively wide with respect to the mean. CONCLUSIONS: This calibrated minimally invasive (i.e. radial arterial line and peripheral IV) technique demonstrated low bias compared with CCI measured by PAC. However, the relatively wide confidence limits indicate that differences in the two measurements could still be clinically significant.

Bonding of stainless steel brackets to enamel with a new self-etching primer.

The purpose of this study was to measure the shear bond strength of stainless steel brackets bonded to enamel in vitro with a recently developed self-etching primer (Transbond Plus Self Etching Primer, 3M Unitek, Monrovia, Calif). Forty-eight extracted human teeth were obtained and randomly divided into 4 groups of 12: (1) control group with a conventional etchant and separate primer, (2) experimental group with the self-etching primer, left for 15 seconds before bonding, (3) same as group 2, but with the primer left for 2 minutes before bonding, (4) same as group 2, but with the primer left for 10 minutes before bonding. For each group, stainless steel brackets were mounted onto the prepared enamel, stored for 24 hours at 37 degrees C, and tested in a testing machine with a crosshead speed of 1 mm/min. There was no significant difference in the bond strength between the 4 groups as determined by analysis of variance (ANOVA) (P <.05). Under the conditions of these experiments, a 10-minute delay in bonding after application of the self-etching primer might not be deleterious to adhesion.