Citations

We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371). This national multi-institutional study is ongoing.

Abstract Lichen planopilaris ( LPP ) is a rare form of cicatricial alopecia that has occasionally been reported in children. Because of the limited number of patients reported, little information is available about demographic characteristics, clinical presentation, or treatment options for these patients. A retrospective chart review of LPP cases in patients under 18 years of age from 1976 to 2013 was performed to further define clinicopathologic features of pediatric LPP . Four pediatric LPP patients ages 13 to 16 years were identified (three male, one female). One patient had scalp pruritus and one had other cutaneous findings of lichen planus ( LP ). Perifollicular scale and scarring were the most common physical examination findings, although changes mimicking those of alopecia areata were observed. Three patients were treated with topical or intralesional steroids. One patient was treated with minocycline. Histopathologic findings included perifollicular interface and perifollicular fibrosis in all cases. There was focal interfollicular interface in two cases and mild dermal mucin in one case. LPP is exceedingly rare in children. It may be misdiagnosed as alopecia areata in children because of the lack of symptoms and other features of LP . There should be a high index of suspicion for LPP in children with alopecia that is unresponsive to standard treatment or who have findings that are atypical for more common childhood alopecias.

Background— Congestion is the most frequent cause for hospitalization in acute decompensated heart failure. Although decongestion is a major goal of acute therapy, it is unclear how the clinical components of congestion (eg, peripheral edema, orthopnea) contribute to outcomes after discharge or how well decongestion is maintained. Methods and Results— A post hoc analysis was performed of 496 patients enrolled in the Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trials during hospitalization with acute decompensated heart failure and clinical congestion. A simple orthodema congestion score was generated based on symptoms of orthopnea (≥2 pillows=2 points, <2 pillows=0 points) and peripheral edema (trace=0 points, moderate=1 point, severe=2 points) at baseline, discharge, and 60-day follow-up. Orthodema scores were classified as absent (score of 0), low-grade (score of 1–2), and high-grade (score of 3–4), and the association with death, rehospitalization, or unscheduled medical visits through 60 days was assessed. At baseline, 65% of patients had high-grade orthodema and 35% had low-grade orthodema. At discharge, 52% patients were free from orthodema at discharge (score=0) and these patients had lower 60-day rates of death, rehospitalization, or unscheduled visits (50%) compared with those with low-grade or high-grade orthodema (52% and 68%, respectively; P =0.038). Of the patients without orthodema at discharge, 27% relapsed to low-grade orthodema and 38% to high-grade orthodema at 60-day follow-up. Conclusions— Increased severity of congestion by a simple orthodema assessment is associated with increased morbidity and mortality. Despite intent to relieve congestion, current therapy often fails to relieve orthodema during hospitalization or to prevent recurrence after discharge. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT00608491, NCT00577135.

Abstract Rationale Most immunocompetent patients diagnosed with latent tuberculosis infection (LTBI) will not progress to tuberculosis (TB) reactivation. However, current diagnostic tools cannot reliably distinguish nonprogressing from progressing patients a priori, and thus LTBI therapy must be prescribed with suboptimal patient specificity. We hypothesized that LTBI diagnostics could be improved by generating immunomarker profiles capable of categorizing distinct patient subsets by a combinatorial immunoassay approach. Objectives A combinatorial immunoassay analysis was applied to identify potential immunomarker combinations that distinguish among unexposed subjects, untreated patients with LTBI, and treated patients with LTBI and to differentiate risk of reactivation. Methods IFN-γ release assay (IGRA) was combined with a flow cytometric assay that detects induction of CD25+CD134+ coexpression on TB antigen–stimulated T cells from peripheral blood. The combinatorial immunoassay analysis was based on receiver operating characteristic curves, technical cut-offs, 95% bivariate normal density ellipse prediction, and statistical analysis. Risk of reactivation was estimated with a prediction formula. Measurements and Main Results Sixty-five out of 150 subjects were included. The combinatorial immunoassay approach identified at least four different T-cell subsets. The representation of these immune phenotypes was more heterogeneous in untreated patients with LTBI than in treated patients with LTBI or unexposed groups. Patients with IGRA(+) CD4+CD25+CD134+ T-cell phenotypes had the highest estimated reactivation risk (4.11 ± 2.11%). Conclusions These findings suggest that immune phenotypes defined by combinatorial assays may potentially have a role in identifying those at risk of developing TB; this potential role is supported by risk of reactivation modeling. Prospective studies will be needed to test this novel approach.

This present case pertains to a 48-year-old woman with a history of antiphospholipid syndrome, who presented with progressive fatigue, generalized weakness, and orthopnea acutely. She had a prior diagnosis of antiphospholipid syndrome with recurrent deep vein thromboses (DVTs) and repeated demonstration of lupus anticoagulants. She presented in cardiogenic shock with markedly elevated troponin and global myocardial dysfunction on echocardiography, and cardiac catheterization revealed minimal disease. Cardiac magnetic resonance imaging was performed, which revealed findings of perfusion defects and microvascular obstruction, consistent with the pathophysiology of catastrophic antiphospholipid syndrome (CAPS). Diagnosis was made based on supportive imaging, including head magnetic resonance imaging (MRI) revealing multifocal, acute strokes; microvascular thrombosis in the dermis; and subacute renal infarctions. The patient was anticoagulated with intravenous unfractionated heparin and received high-dose methylprednisolone, plasmapheresis, intravenous immunoglobulin, and one dose each of rituximab and cyclophosphamide. She convalesced with eventual myocardial recovery after a complicated course. The diagnosis of CAPS relies on the presence of (1) antiphospholipid antibodies and (2) involvement of multiple organs in a microangiopathic thrombotic process with a close temporal association. The myocardium is frequently affected, and heart failure, either as the presenting symptom or cause of death, is common. Despite echocardiographic evidence of myocardial dysfunction in such patients, MRIs of CAPS have not previously been reported. This case highlights the utility in assessing the involvement of the myocardium by the microangiopathic process with MRI. Because the diagnosis of CAPS requires involvement in multiple organ systems, cardiac MRI is likely an underused tool that not only reaffirms the pathophysiology of CAPS, but could also clue clinicians in to the possibility of a diffuse thrombotic process.

Analysis of the induced stress on undoped and boron-doped diamond (BDD) thin films by confocal Raman microscopy is performed in this study to investigate its correlation with sample chemical composition and the substrate used during fabrication. Knowledge of this nature is very important to the issue of long-term stability of BDD coated neurosurgical electrodes that will be used in fast-scan cyclic voltammetry, as potential occurrence of film delaminations and dislocations during their surgical implantation can have unwanted consequences for the reliability of BDD-based biosensing electrodes. To achieve a more uniform deposition of the films on cylindrically-shaped tungsten rods, substrate rotation was employed in a custom-built chemical vapor deposition reactor. In addition to visibly preferential boron incorporation into the diamond lattice and columnar growth, the results also reveal a direct correlation between regions of pure diamond and enhanced stress. Definite stress release throughout entire film thicknesses was found in the current Raman mapping images for higher amounts of boron addition. There is also a possible contribution to the high values of compressive stress from sp2 type carbon impurities, besides that of the expected lattice mismatch between film and substrate.