Citations

“Later onset” of systemic mastocytosis (SM) has been associated with a poorer prognosis. We examined clinical and laboratory findings, associated disorders, and survival in an older mastocytosis population. After receiving Mayo Clinic Institutional Review Board approval, we identified 42 patients aged 70 years and older at the time of diagnosis of SM. Associated disorders, cytogenetic abnormalities, laboratory findings, and survival were recorded. Only 10 patients had no associated hematologic disorder. Single or multiple chromosomal abnormalities, exclusive of the KIT Asp816Val mutation, were detected in eight patients (19%). KIT Asp816Val mutation was present in 14 patients, negative in three, and not tested in 25. Slight to marked bone marrow hypercellularity was observed in 33 patients (79%). Concurrent hematologic abnormalities included chronic myelomonocytic leukemia (n = 7), acute myelocytic leukemia (n = 1), myelodysplastic syndrome (MDS; n = 7), eosinophilia (n = 7), myelofibrosis (n = 1), myeloproliferative disorder (n = 1), multiple myeloma (n = 1), B‐cell lymphoma (n = 1), and thrombocytopenia (n = 4). Eight patients had a hematologic disorder that preceded the diagnosis of SM. Tryptase levels were elevated in 38 of 39 patients tested. Survival from the diagnosis of SM was poor for patients with associated thrombocytopenia, leukemias, and MDS. In conclusion, patients with SM diagnosed at age 70 or older have an increased risk of secondary hematologic disorders and abnormal laboratory findings. Cytogenetic abnormalities are common, and survival is short in many SM patients with associated leukemias, MDS, or eosinophilia. Am. J. Hematol. 88:406–408, 2013. © 2013 Wiley Periodicals, Inc.

Objective— Endothelial outgrowth cells (EOC) decrease inflammation and improve endothelial repair. Inflammation aggravates kidney injury in renal artery stenosis (RAS), and may account for its persistence upon revascularization. We hypothesized that EOC would decrease inflammatory (M1) macrophages and improve renal recovery in RAS. Approach and Results— Pigs with 10 weeks of RAS were studied 4 weeks after percutaneous transluminal renal angioplasty (PTRA+stenting) or sham, with or without adjunct intrarenal delivery of autologous EOC (10×10 6 ), and compared with similarly treated normal controls (n=7 each). Single-kidney function, microvascular and tissue remodeling, inflammation, oxidative stress, and fibrosis were evaluated. Four weeks after PTRA, EOC were engrafted in injected RAS-kidneys. Stenotic-kidney glomerular filtration rate was restored in RAS+EOC, RAS+PTRA, and RAS+PTRA+EOC pigs, whereas stenotic-kidney blood flow and angiogenesis were improved and fibrosis attenuated only in EOC-treated pigs. Furthermore, EOC increased cell proliferation and decreased the ratio of M1 (inflammatory)/M2 (reparative) macrophages, as well as circulating levels and stenotic-kidney release of inflammatory cytokines. Cultured-EOC released microvesicles in vitro and induced phenotypic switch (M1-to-M2) in cultured monocytes, which was inhibited by vascular endothelial growth factor blockade. Finally, a single intrarenal injection of rh-vascular endothelial growth factor (0.05 μg/kg) in 7 additional RAS pigs also restored M1/M2 ratio 4 weeks later. Conclusions— Intrarenal infusion of EOC after PTRA induced a vascular endothelial growth factor–mediated attenuation in macrophages inflammatory phenotype, preserved microvascular architecture and function, and decreased inflammation and fibrosis in the stenotic kidney, suggesting a novel mechanism and therapeutic potential for adjunctive EOC delivery in experimental RAS to improve PTRA outcomes.

A Nobel pursuit

Background: Single infusions of ketamine have been used successfully to achieve improvement in depressed patients. Side effects during the infusions have been common. It is not known whether serial infusions or lower infusion rates result in greater efficacy. Methods: Ten depressed patients were treated with twice weekly ketamine infusions of ketamine 0.5 mg/kg administered over 100 min until either remission was achieved or four infusions were given. Side effects were assessed with the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). Patients were followed naturalistically at weekly intervals for four weeks after completion of the infusions. Results: Five of 10 patients achieved remission status. There were no significant increases on the BPRS or YMRS. Two of the remitting patients sustained their improvement throughout the four week follow-up period. Conclusions: Ketamine infusions at a lower rate than previously reported have demonstrated similar efficacy and excellent tolerability and may be more practically available for routine clinical care. Serial ketamine infusions appear to be more effective than a single infusion. Further research to test relapse prevention strategies with continuation ketamine infusions is indicated.

Proton magnetic resonance spectroscopy (1H‐MRS) is a safe, noninvasive way of quantifying in vivo biochemical and metabolite concentration levels in individuals withAutismSpectrumDisorders (ASD). Findings to date suggestASDis associated with widespread reduction inN‐acetylaspartate (NAA), creatine plus phosphocreatine (Cr), choline‐containing compounds (Cho),myo‐inositol (mI), and glutamate plus glutamine plus gamma‐Aminobutyric Acid (Glx); however, variable findings, and even substantial increases, are not uncommon depending on the study and/or region‐of‐interest. Widespread reduction ofNAA,Cr,Cho,mI, andGlxinASDlikely reflects impaired neuronal function and/or metabolism related to abnormal neurodevelopmental processes. Future studies should attempt to relate1H‐MRSfindings to histological findings and control for variability in subject age and functioning level; this would assist in evaluating the relationship between1H‐MRSmetabolic levels and neuronal and glial cell densities, as well as neurodevelopmental process associated withASD. Furthermore, more longitudinal1H‐MRSstudies are needed in both control andASDsubjects to attempt to standardize metabolite levels across different developmental periods in well‐defined endophenotypes. This will provide for a standard rubric for which metabolic aberrations (as well as treatment responses) can be measured. With higher magnetic field strengths and spectral‐editing techniques capable of quantifying less‐concentrated metabolites,1H‐MRSwill continue to be an important tool inASDresearch.Autism Res2013, 6: 119–133.© 2013 International Society for Autism Research, Wiley Periodicals, Inc.

ObjectivesThe purpose of this study was to evaluate the left main (LM) coronary artery anatomy using three‐dimensional (3D) quantitative coronary angiography (QCA) software as compared to intravascular ultrasound (IVUS).BackgroundPercutaneous intervention of the LM coronary artery is becoming more common in selected patients with LM coronary artery disease (CAD). Quantification of LM CAD by conventional angiography can be difficult. IVUS is considered the gold standard to evaluate LM anatomy and severity of CAD but entails additional steps, catheters, and expertise. Our objective was to compare a novel quantitative angiographic analysis system with IVUS for LM anatomy.MethodsFifty five patients underwent both coronary angiography and IVUS of the LM. LM measurements were analyzed with 3D QCA (IC‐PRO, Paieon, Israel) software using IVUS as the reference standard. The measurements included proximal, middle, distal minimal luminal diameter (MLD) and area. Additionally, lesion MLD, minimal luminal area were recorded by both systems. Bland–Altman plots were used to investigate agreement between the two imaging systems.ResultsOf the 55 patients in our cohort, average age was 66 ± 11 years (25% female). By Bland‐Altman analysis there was very good agreement between 3D QCA and IVUS for measures of MLD and minimal lumen area (MLA). However, there was poor concordance in the estimation of plaque burden between the two methods.ConclusionsOur data demonstrate that 3D QCA software has fair agreement when compared with IVUS for imaging of LM MLD and MLA. These results suggest that 3D QCA could potentially be helpful to guide intervention of the LM. © 2012 Wiley Periodicals, Inc.

Background: Current recommendations for surgical management of early-stage breast cancer include breast-conserving surgery with postoperative irradiation. However, studies show that mastectomy is still being used by women with early-stage breast cancer. Methods: Review of the medical literature published between 2000 and 2010 to determine the factors associated with the decision of patients for surgical treatment in early-stage breast cancer. Results: The following patient characteristics affect the surgical decision-making process in early-stage breast cancer: age, socioeconomic factors, geographic area in which the patient lives, proximity to a radiation therapy center, testing for BRCA gene, breast imaging, and decision aids. Conclusions: Of increasing importance in the decision making about treatment of women with early-stage breast cancer are the woman's perception of having a surgical choice and the influence of that choice on postoperative quality of life.

AbstractBackground and AimsPositron emission tomography with computed tomography (PET/CT) has been used to detect metastasis in the diagnosis of esophageal adenocarcinoma (EAC). However, the utility of PET/CT to assess primary tumor for endoscopic resectability and prognosis in early EAC remains unclear. We conducted a retrospective study to determine the association of PET/CT findings with histopathological tumor invasion depth and survival outcomes.MethodsEAC patients who underwent PET/CT followed by endoscopic mucosal resection (EMR) were included. Pathology on EMR and survival outcomes from a prospectively maintained database was retrieved. Two radiologists independently reviewed the PET/CT using the following parameters: detection of malignancy, fluorodeoxyglucose (FDG) uptake intensity, FDG focality, FDG eccentricity, esophageal thickness, maximal standard uptake value (SUVmax), and SUVmax ratio (lesion/liver).ResultsThere were 72 eligible patients: 42 (58.3%) had T1a lesions, and 30 (41.7%) had ≥ T1b. Only SUVmax ratio was associated with tumor invasion depth (odds ratio = 2.77, 95% confidence interval 1.26–7.73, P = 0.0075). Using a cut‐off of 1.48, the sensitivity and specificity of SUVmax ratio for identification of T1a lesions were 43.3% and 80.9%, respectively. Adjusting the SUVmax ratio to 2.14, 16.7% (5/30) of ≥ T1b patients were identified without any false‐positive cases. Multivariate analysis showed SUVmax ratio, Charlson comorbidity index, and esophagectomy were independent predictors for survival.ConclusionsSUVmax ratio (lesion/liver) is more accurate in predicting endoscopic resectability and mortality for EAC than other PET/CT parameters and appears promising as a useful adjunct to the current diagnostic work‐up.