This report presents a series of 5 pediatric patients with disseminated pilocytic astrocytomas and frequent nonfusion activating mutations. Genetic variants in these patients' tumors include BRAF p.Val600Glu, BRAF p.Val600Asp, and KRAS p.Gly60_Gln62ins7. The 2 patients with -mutated tumors were treated with dabrafenib or a combination of dabrafenib plus trametinib. The patients had either near complete resolution of the primary tumor (BRAF p.Val600Glu) or a stable primary tumor (BRAF p.Val600Asp). Both patients showed improvement in leptomeningeal dissemination without significant toxicity. Genomic testing of disseminated pilocytic astrocytomas, particularly those arising at extracerebellar locations, may result in the identification of mutations associated with ERK/MAPK activation. Patients with these activating mutations may benefit from targeted therapies.
Drobysheva A, Ahmad M, White R, Wang H, Leenen FH. Cardiac sympathetic innervation and PGP9.5 expression by cardiomyocytes after myocardial infarction: effects of central MR blockade. Am J Physiol Heart Circ Physiol 305: H1817-H1829, 2013. First published October 11, 2013; doi:10.1152/ajpheart.00445.2013.-Central mechanisms involving mineralocorticoid receptor (MR) activation contribute to an increase in sympathetic tone after myocardial infarction (MI). We hypothesized that this central mechanism also contributes to cardiac sympathetic axonal sprouting and that central MR blockade reduces cardiac sympathetic hyperinnervation post-MI. Post-MI, tyrosine hydroxylase (TH) and norepinephrine transporter protein content in the noninfarcted base of the heart remained unaltered. In contrast, protein gene product (PGP)9.5 protein was increased twofold in the base of the heart and sixfold in the peri-infarct area at 1 wk post-MI and was associated with increased ubiquitin expression. These changes persisted to a lesser extent at 4 wk post-MI and were no longer present at 12 wk. Cardiac myocytes rather than sympathetic axons were the main source of this elevated PGP9.5 expression. At 7-10 days post-MI, in the peri-infarct area, sympathetic hyperinnervation was observed with a fourfold increase in growth-associated protein 43, a twofold increase in TH, and a 50% increase in PGP9.5-positive fibers compared with the epicardial side of the left ventricle in sham rats. Central infusion of the MR blocker eplerenone markedly attenuated these increases in nerve densities but did not affect overall cardiac PGP9.5 and ubiquitin protein overexpression. We conclude that central MR activation contributes to sympathetic hyperinnervation, possibly by decreasing cardiac sympathetic activity post-MI, or by affecting other mechanisms, such as the expression of nerve growth factor. Marked PGP9.5 expression occurs in cardiomyocytes early post-MI, which may contribute to the increase in ubiquitin. myocardial infarction; cardiac sympathetic hyperinnervation; brain mineralocorticoid receptors; eplerenone; ubiquitin; protein gene product 9.5 CARDIAC REMODELING after myocardial infarction (MI) affects both infarcted and noninfarcted areas of the heart and contributes to the impairment of ventricular performance (19,43,44). Cardiac sympathetic hyperactivity enhances maladaptive cardiac remodeling post-MI and plays a major role in the development of chronic heart failure (CHF) (5, 31). In humans with mild CHF, there is a selective increase in cardiac sympathetic activity, which is followed by augmented sympathetic outflow to skeletal muscle and the kidneys as CHF progresses (16,38). In rats, direct recordings from cardiac sympathetic nerves demonstrate that cardiac sympathetic nerve activity (CSNA) increased twofold within hours after MI (40). In conscious sheep, CSNA was significantly increased by the second hour post-MI and remained elevated for at least 1 wk (14).Increased CSNA may also contribute to the development of cardiac sympathetic hyperi...
Granulomatosis with polyangiitis is rare in children. We report a case of a 12-year-old male who presented with new symptoms of left eyelid swelling and ptosis. Magnetic resonance imaging showed an enhancing orbital mass suspicious for a neoplasm. Excisional biopsy was performed. Microscopic examination revealed fibrovascular tissue with dense collagenous fibrosis and mixed inflammatory infiltrate that included many plasma cells. Many small and medium-sized blood vessels showed granulomatous and necrotizing vasculitis with disruption of the vessel walls and fibrinoid necrosis. Immunostain for IgG highlighted the numerous plasma cells, approximately 50% of which were positive for IgG4 immunostain. A diagnosis of granulomatosis with polyangiitis was suggested, with recommendation of serologic testing for anti-neutrophil cytoplasmic antibodies. Serum anti-neutrophil cytoplasmic antibodies were borderline high with a cytoplasmic staining pattern. The patient improved with steroid and methotrexate therapy. Granulomatosis with polyangiitis can present as an orbital mass in up to 30% of children. It may be misdiagnosed as IgG4-related disease since the inflammatory background in both conditions may be rich in plasma cells with a high proportion of IgG4+ plasma cells, and accompanied by fibrosis and obliterated blood vessels. The differential diagnosis in this location should also include inflammatory pseudotumor and inflammatory myofibroblastic tumor. Knowledge of this unusual manifestation of granulomatosis with polyangiitis and its diagnostic pitfalls can facilitate early diagnosis and treatment.
Context.— Smart glasses are a wearable technology that enable hands-free data acquisition and entry. Objective.— To develop a surgical pathology grossing application on a smart glass platform. Design.— An existing logistics software for the Google Glass Enterprise smart glass platform was used to create surgical pathology grossing protocols. The 2 grossing protocols were developed to simulate grossing a complex (heart) and a simple (kidney) specimen. For both protocols, users were visually prompted by the smart glass device to perform each task, record measurements, or document the field of view. In addition to measuring the total time of the protocol performance, each substep within the protocol was automatically recorded. Subsequently, a report was generated that contained the dictation, images, voice recordings, and the timing of each step. The application was tested by 3 users using the 2 grossing protocols. The users were tracked across 3 grossing procedures for each protocol. Results.— For the complex specimen grossing the average time across repeated procedures was not significantly different between users ( P = .999). However, when grossing times of the complex specimen were compared for repeated performances of the same user, a significant reduction in grossing times was observed with each repetition ( P = .002). For the simple specimen, the average grossing time across multiple attempts was different among users ( P = .03); however, no improvement in grossing time was observed with repeated performance ( P = .499). Conclusions.— Augmented reality based grossing applications can provide automated data collection to track the changes in grossing performance over time.
In the clinical classification of cholelithiasis, biliary sludge (BS) is distinguished as the pre-stone stage. Ursodeoxycholic acid (UDCA) is a drug with an evidence base for effective and safe effects on BS. The therapeutic equivalence of various UDCA drugs remains an important issue for clinical practice. Aim. To conduct a comparative analysis of the effectiveness of the use of UDCA: Ursofalk with other UDCA drugs for the treatment of BS in a fixed dose of 10 mg/kg of body weight. Material and methods. The observation group consisted of 225 patients with various types of BS. In randomized groups, the comparison of the effectiveness of UDCA drugs in the dissolution of BS was determined by the data of ultrasound of the gallbladder. Dynamic ultrasound cholecystography using a standardized technique was performed to study the effect of the compared drugs on the contractile function of the liver. When analyzing the impact of ursotherapy on the clinical manifestations of BS, the dynamics of biliary pain syndrome and dyspeptic disorders were evaluated. Results. A comparative analysis of the effectiveness of UDCA drugs for BS lysis with a high degree of confidence established the advantage of Ursofalk: after 3 months in 80%, and after 6 months of therapy in 95.65% of patients, a regression of BS was detected. In the group of patients who took other UDCA, the corresponding indicators were 46.36% and 67.27%. The greatest effectiveness of ursotherapy was demonstrated in the BS variant by the type of suspension of hyperechogenic particles, the lowest in the variant by the type of putty-like bile in the form of mobile or fixed clots. In the last variant of BS, the relationship between the success of lysis with the extension of the UDCA intake period to 6 months and the preferred choice of Ursofalk was traced. Normalization of the contractile function of the gallbladder was noted in patients who took Ursofalk. Conclusion. From the standpoint of therapeutic effectiveness, the drug of choice for the treatment of BS, regardless of its type, is Ursofalk, which has proven the best dynamics of BS litolysis, recovery of the contractile function of the gastrointestinal tract, and relief of clinical symptoms.
Recently, the rates of contralateral prophylactic mastectomy (CPM) have increased significantly with no clear evidence of improvement in overall survival or breast cancer (BC) specific survival. In 2016, American Society of Breast Surgeons (ASBS) provided a consensus statement regarding when CPM should be-, can be- or may be offered and when it should be discouraged. In light of new recommendations, our study aimed to review factors that influenced the choice of CPM at our institution. Methods: This retrospective study was approved by the IRB. Patients who underwent CPM between January 2011 and May 2014 were included. Medical records were reviewed for documentation of risk factors that led to CPM. Patients were stratified into four categories based on the consensus statement. CPM “should be considered” included carriers of BRCA1/2 mutation, patients with strong FH (2 or more first degree relatives with BC) but not tested for BRCA and patients with history of mantle radiation; CPM “can be considered” included patients with intermediate FH (one first degree or multiple second/third degree relatives with BC), carriers of non-BRCA gene mutation, patients with prior history of BC and patients with strong FH but tested negative for BRCA; CPM “may be considered" included patients with psychological factors, those who denied adjuvant therapy and patients with multicentric disease in the index side. CPM “should be discouraged” included patients with advanced disease at the time of diagnosis, patients with weak FH (one second or third degree relative with BC) and patients with no significant FH or unknown FH. Results: Between January 2011 and May 2014, CPM was performed in 261 women ranging from 24 to 83 years (mean, 50 years). The number and percentage of women in each risk group is summarized in Table. Discussion: Based on the results, only 13% of the 261 women satisfied the criteria for when CPM "should be considered”, 38% for when CPM "can be or may be considered”, and in the remaining 49% CPM should have been discouraged. In light of the growing controversy regarding the overall benefit of CPM, it is important that the women with average-risk are well informed about the surgical risks vs. the benefits of CPM. Summary of the risks factors associated with contralateral prophylactic mastectomy (n=261)CPM should be considered for those at significant risk of CBC (total 13%) Carriers for BRCA 1/2 mutation2911.1%Strong Family history (patient not tested for BRCA)20.8%History of mantle radiation31.1%CPM can be considered for those at lower risk of CBC (total 30.6%) Intermediate family history6023%Carriers for non-BRCA gene mutation31.1%History of prior breast carcinoma135%Strong Family history, BRCA negative41.5%CPM may be considered for other reasons (total 7.6%) Psychological factors62.3%Patient denied adjuvant chemo or radiation therapy31.1%Multicentric disease in the index breast114.2%CPM should be discouraged (48.8%) Advanced disease at diagnosis41.5%Weak family history7829.8%No family history4115.6%Unknown family history, no other significant personal history51.9%CPM: contralateral prophylactic mastectomy; CBC: contralateral breast cancer Citation Format: Drobysheva A, Butt Y, Sahoo S. Assessment of risk factors in women undergoing contralateral prophylactic mastectomy after breast cancer diagnosis: Experience at an academic medical center [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-14.
ObjectivesGraves’ disease (GD) is rare in children under age five years. Antithyroid drugs are typically first-line therapy but carry the risks of agranulocytosis and liver dysfunction.Case presentationA male infant with multiple congenital anomalies, left ventricular hypertrophy, and neurologic dysfunction developed GD at five months of life. The presence of chronic hepatitis complicated medical management. Potassium iodide was effective temporarily, but urgent thyroidectomy was required at nine months of age. Postoperatively, the patient developed a thyroid function pattern consistent with impaired pituitary sensitivity to thyroid hormone (TH) that responded to the addition of liothyronine. Exome sequencing revealed a heterozygous de novo duplication of the ATAD3 gene cluster, suggesting a possible mitochondrial disorder.ConclusionsThis case describes the youngest child to date to be diagnosed with endogenous GD and to successfully undergo definitive treatment with thyroidectomy. An underlying defect in mitochondrial function is suspected, suggesting a potential novel pathophysiologic link to early-onset thyroid autoimmunity. Additionally, this case illustrated the development of impaired pituitary sensitivity to TH following thyrotoxicosis of postnatal onset, which may contribute to our understanding of hypothalamic-pituitary-thyroid (HPT) axis development.
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