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2.
Artigo em Inglês | MEDLINE | ID: mdl-32203069

RESUMO

BACKGROUND: Statins inhibit HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway. Epidemiological and pre-clinical evidence support an association between statin use and delayed prostate cancer (PCa) progression. Here, we evaluated the effects of neoadjuvant fluvastatin treatment on markers of cell proliferation and apoptosis in men with localized PCa. METHODS: Thirty-three men were treated daily with 80 mg fluvastatin for 4-12 weeks in a single-arm window-of-opportunity study between diagnosis of localized PCa and radical prostatectomy (RP) (ClinicalTrials.gov: NCT01992042). Percent Ki67 and cleaved Caspase-3 (CC3)-positive cells in tumor tissues were evaluated in 23 patients by immunohistochemistry before and after treatment. Serum and intraprostatic fluvastatin concentrations were quantified by liquid chromatography-mass spectrometry. RESULTS: Baseline characteristics included a median prostate-specific antigen (PSA) level of 6.48 ng/mL (IQR: 4.21-10.33). The median duration of fluvastatin treatment was 49 days (range: 27-102). Median serum low-density lipoprotein levels decreased by 35% after treatment, indicating patient compliance. Median PSA decreased by 12%, but this was not statistically significant in our small cohort. The mean fluvastatin concentration measured in the serum was 0.2 µM (range: 0.0-1.1 µM), and in prostatic tissue was 8.5 nM (range: 0.0-77.0 nM). At these concentrations, fluvastatin induced PCa cell death in vitro in a dose- and time-dependent manner. In patients, fluvastatin treatment did not significantly alter intratumoral Ki67 positivity; however, a median 2.7-fold increase in CC3 positivity (95% CI: 1.9-5.0, p = 0.007) was observed in post-fluvastatin RP tissues compared with matched pre-treatment biopsy controls. In a subset analysis, this increase in CC3 was more pronounced in men on fluvastatin for >50 days. CONCLUSIONS: Fluvastatin prior to RP achieves measurable drug concentrations in prostatic tissue and is associated with promising effects on tumor cell apoptosis. These data warrant further investigation into the anti-neoplastic effects of statins in prostate tissue.

3.
Sci Immunol ; 5(45)2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32139586

RESUMO

B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE+ and non-IgE-expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE+ B lineage cells in food allergy.

4.
Heart Rhythm ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32036023

RESUMO

BACKGROUND: Unexplained cardiac arrest (UCA) is rare in children. Despite investigations, the etiology in up to one-half of patients remains unknown. OBJECTIVE: The purpose of this study was to assess the management and outcomes of pediatric UCA survivors through the Canadian Pediatric Heart Rhythm Network. METHODS: A retrospective case series of children (age 1-19 years) who presented with UCA between January 1, 2004, and November 1, 2017, was conducted. Patients with known heart disease pre-UCA were excluded. UCA details, investigations, genetic test results, treatment, implantable cardioverter-defibrillator (ICD) data, subsequent diagnoses, and family screening data were collected. RESULTS: Forty-six patients (61% male) were survivors of sudden unexpected death and met inclusion criteria at 8 participating sites. Median age at UCA was 13.8 years (interquartile range [IQR] 9-16 years). Baseline retrievable investigations included electrocardiogram (96%), echocardiogram (85%), exercise stress test (73%), and cardiac magnetic resonance imaging (57%). The presumed etiology for the UCA was identified in 24 (52%), mainly long QT syndrome or catecholaminergic polymorphic ventricular tachycardia. Genetic testing was performed in 33 of 46 (72%), with pathogenic/likely pathogenic variants identified in 13 of 33 (39%) and variants of uncertain significance in 8 of 33 (24%). ICDs were implanted in 35 of 46 (76%). Over median follow-up of 36 months (IQR 17-57 months), 8 of 35 had arrhythmia events captured on device interrogation. Families of 26 of 46 patients(57%) underwent screening, leading to a cardiac diagnosis in 6 of 26 families. CONCLUSION: A cause for UCA was not identified in nearly 50% of patients despite extensive investigations, including cascade screening. A large proportion (75%) of ICD shocks occurred in patients without a diagnosis.

5.
Urology ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32004556

RESUMO

OBJECTIVE: To compare a simultaneous vs sequential approach to residual post chemotherapy mass resections in metastatic testis cancer. METHODS: A retrospective review was performed of patients who underwent retroperitoneal and thoracic/cervical resection of post chemotherapy residual masses between 2002 and 2018. Group 1: "Simultaneous" (Combined Retroperitoneal and Thoracic/Cervical resections on the same date); Group 2: "Sequential" (Retroperitoneal and Thoracic/Cervical resections at separate dates). RESULTS: During the study period, 35 simultaneous and 17 sequential resections were performed. The median age at surgery was 28 years (Range 16-61). The median follow-up from last surgical procedure was 62.7 months (Range 0.4-194). Histology revealed teratoma in 38 (73.1%) patients, necrosis in 8 (15.4%) and viable tumor in 6 (11.5%). Discordant pathology findings between thoracic/cervical and abdominal resections were noted in 16 (30.8%) patients. No differences were observed between the simultaneous vs sequential groups in median operating time (585 minutes vs 545 minutes, P = .64), blood loss (1300 vs 1300 mls, P = .42), or length of stay (9 vs 11 days, P = .14). There was no difference between the 5-year (65.7% vs 68.6%) relapse-free survival between the 2 groups (P = .84) or the 5-year (88.6% vs 100%) overall and disease-specific survival (P = .25). CONCLUSION: Simultaneous resection of retroperitoneal and thoracic/cervical post chemotherapy metastases is a feasible in some patients. It requires multidisciplinary collaboration and a longer primary procedure.

6.
PLoS One ; 15(2): e0228642, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027714

RESUMO

Cerebral Blood Flow Velocity waveforms acquired via Transcranial Doppler (TCD) can provide evidence for cerebrovascular occlusion and stenosis. Thrombolysis in Brain Ischemia (TIBI) flow grades are widely used for this purpose, but require subjective assessment by expert evaluators to be reliable. In this work we seek to determine whether TCD morphology can be objectively assessed using an unsupervised machine learning approach to waveform categorization. TCD beat waveforms were recorded at multiple depths from the Middle Cerebral Arteries of 106 subjects; 33 with Large Vessel Occlusion (LVO). From each waveform, three morphological features were extracted, quantifying onset of maximal velocity, systolic canopy length, and the number/prominence of peaks/troughs. Spectral clustering identified groups implicit in the resultant three-dimensional feature space, with gap statistic criteria establishing the optimal cluster number. We found that gap statistic disparity was maximized at four clusters, referred to as flow types I, II, III, and IV. Types I and II were primarily composed of control subject waveforms, whereas types III and IV derived mainly from LVO patients. Cluster morphologies for types I and IV aligned clearly with Normal and Blunted TIBI flows, respectively. Types II and III represented commonly observed flow-types not delineated by TIBI, which nonetheless deviate from normal and blunted flows. We conclude that important morphological variability exists beyond that currently quantified by TIBI in populations experiencing or at-risk for acute ischemic stroke, and posit that the observed flow-types provide the foundation for objective methods of real-time automated flow type classification.

7.
Am J Hum Genet ; 106(2): 143-152, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32032513

RESUMO

Advances in genomics have transformed our ability to identify the genetic causes of rare diseases (RDs), yet we have a limited understanding of the mechanistic roles of most genes in health and disease. When a novel RD gene is first discovered, there is minimal insight into its biological function, the pathogenic mechanisms of disease-causing variants, and how therapy might be approached. To address this gap, the Canadian Rare Diseases Models and Mechanisms (RDMM) Network was established to connect clinicians discovering new disease genes with Canadian scientists able to study equivalent genes and pathways in model organisms (MOs). The Network is built around a registry of more than 500 Canadian MO scientists, representing expertise for over 7,500 human genes. RDMM uses a committee process to identify and evaluate clinician-MO scientist collaborations and approve 25,000 Canadian dollars in catalyst funding. To date, we have made 85 clinician-MO scientist connections and funded 105 projects. These collaborations help confirm variant pathogenicity and unravel the molecular mechanisms of RD, and also test novel therapies and lead to long-term collaborations. To expand the impact and reach of this model, we made the RDMM Registry open-source, portable, and customizable, and we freely share our committee structures and processes. We are currently working with emerging networks in Europe, Australia, and Japan to link international RDMM networks and registries and enable matches across borders. We will continue to create meaningful collaborations, generate knowledge, and advance RD research locally and globally for the benefit of patients and families living with RD.

8.
PLoS One ; 15(2): e0228751, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049976

RESUMO

BACKGROUND: Primary cutaneous CD30+ lymphoproliferative disorders (CD30CLPD) are the second most common type of cutaneous T cell lymphoma (CTCL) and include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Case reports and small patient series suggest an association of CD30CLPD with atopic disorders. However, the prevalence of atopy in patients with CD30CLPD in retrospective studies depends on patients' recall which is not always reliable. More objective criteria of atopy include evidence of skin reactivity to allergens (positive prick test) and evidence of allergen-specific IgE in serum. This study was undertaken to test the hypothesis that atopy is prevalent in patients with CD30CLPD using serologic criteria of allergen-specific IgE antibodies to aeroallergens and Staphylococcal aureus enterotoxin superantigens (SSAgs). METHODS: We tested serum samples of CD30CLPD for common IgE-specific airborne allergens with the Phadiatop test, which if positive, is regarded as serologic evidence of atopy in adults. Sera were also tested for IgE antibodies reactive to three Staphylococcal enterotoxins with superantigenic properties (SSAg-IgE). Control sera were obtained from adult subjects evaluated for rhino-sinusitis and a negative Phadiatop test. Patients' history of an atopic disorder was obtained by retrospective chart review. FINDINGS: Nearly 50% of patients with the most common LyP types (A and C) had a positive Phadiatop test for allergic sensitization to common airborne allergens, and total serum IgE (IgE-t) was increased compared to non-atopic controls. At the IgE antibody concentration generally used to define serologic atopy (≥ 0.35 kUA/L), 8/31 (26%) samples of CD30CLPD and 7/28 (25%) samples of LyP were reactive to at least one SSAg-IgE compared to 3/52 (6%) control specimens (P = 0.016 and P = 0.028, respectively). TSST1-IgE was detected in 7 (23%) specimens of CD30CLPD, often together with SEB-IgE; SEA-IgE ≥ 0.35 kUA/L was not detected. For control specimens, TSST1-IgE exceeded the 0.35 kUA/L threshold in 3 (6%) specimens. CONCLUSIONS: Patients with LyP types A and C have serologic evidence of atopy against common airborne antigens and SSAgs when compared to control adult subjects who had rhino-sinusitis and a negative Phadiatop test for aero-IgEs. Serologic evidence of atopy exceeded that determined by LyP patients' personal history. The findings support our hypothesis that an atopic diathesis may contribute to the pathogenesis of the most common types of LyP (A and C).

9.
Can Urol Assoc J ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31977306

RESUMO

INTRODUCTION: Active surveillance (AS) is an accepted management strategy for low-risk prostate cancer (PCa), but its role in the management of favorable intermediate-risk PCa remains controversial. Most reports studying the role of AS for these men generally lack long-term followup and include small numbers of patients. Our objective was to report the outcomes of men diagnosed with Gleason grade groups (GGG) 2 and 3 PCa who were managed expectantly. METHODS: Using administrative datasets and pathology reports, we identified all men who were diagnosed with GGG 2 and 3 PCa and managed expectantly between 2002 and 2011 in Ontario, Canada. Outcomes and associated factors were estimated using cumulative incidence function methods and multivariable Cox regression models, respectively. RESULTS: We identified 926 men who were managed expectantly (AS [n=374] or watchful waiting [n=552]). The eight-year cancer-specific survival was 94% and 89% for the AS and watchful waiting cohorts, respectively. Among AS men, 266 (71%) received treatment after a followup of approximately eight years. Cumulative AS discontinuation rates at one and five years were 30.5% and 65.1%, respectively. CONCLUSIONS: Expectant management of GGG 2 and 3 PCa may be an option for certain men. Notably for AS patients, the cancer-specific mortality at eight years was 6%, and over 65% of men underwent treatment within five years. Further studies are required to evaluate which patients, based on disease-specific features and competing health risks, would benefit the most from a conservative strategy.

10.
IEEE Trans Biomed Eng ; 67(3): 883-892, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31217091

RESUMO

OBJECTIVE: Transcranial Doppler (TCD) ultrasonography measures pulsatile cerebral blood flow velocity in the arteries and veins of the head and neck. Similar to other real-time measurement modalities, especially in healthcare, the identification of high-quality signals is essential for clinical interpretation. Our goal is to identify poor quality beats and remove them prior to further analysis of the TCD signal. METHODS: We selected objective features for this purpose including Euclidean distance between individual and average beat waveforms, cross-correlation between individual and average beat waveforms, ratio of the high-frequency power to the total beat power, beat length, and variance of the diastolic portion of the beat waveform. We developed an iterative outlier detection algorithm to identify and remove the beats that are different from others in a recording. Finally, we tested the algorithm on a dataset consisting of more than 15 h of TCD data recorded from 48 stroke and 34 in-hospital control subjects. RESULTS: We assessed the performance of the algorithm in the improvement of estimation of clinically important TCD parameters by comparing them to that of manual beat annotation. The results show that there is a strong correlation between the two, that demonstrates the algorithm has successfully recovered the clinically important features. We obtained significant improvement in estimating the TCD parameters using the algorithm accepted beats compared to using all beats. SIGNIFICANCE: Our algorithm provides a valuable tool to clinicians for automated detection of the reliable portion of the data. Moreover, it can be used as a pre-processing tool to improve the data quality for automated diagnosis of pathologic beat waveforms using machine learning.

11.
Pediatr Allergy Immunol ; 31(2): 186-196, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31301691

RESUMO

BACKGROUND: Hazelnut-specific IgE antibodies (sIgEs) in serum support the diagnosis of hazelnut allergy, but extract-based tests have low diagnostic specificity, commonly leading to over-diagnosis. Measuring sensitization to individual allergen components may enhance the diagnosis of hazelnut allergy. We systematically examined data on diagnostic accuracy of sIgE to commercially available hazelnut components to compare their individual contributions in diagnosing hazelnut allergy. METHODS: Seven databases were searched for diagnostic studies on patients suspected of having hazelnut allergy. Studies employing component-specific IgE testing on patients whose final diagnosis was determined by oral food challenges were included in the meta-analysis. Study quality was assessed as recommended by Cochrane. RESULTS: Seven cross-sectional studies and one case-control study were identified, seven presenting data on children (N = 635), and one on a mixed age population. Overall, the diagnostic accuracies of sIgE to both Cor a 9 and Cor a 14 were significantly higher than for Cor a 1-sIgE (P < .05). In children, the specificity of Cor a 14-sIgE at 0.35 kUA /L cutoff was 81.7% (95% CI 77.1, 85.6), and 67.3% (60.3, 73.6) for Cor a 9-sIgE. The specificities for Cor a 1-sIgE and hazelnut-sIgE were 22.5% (7.4, 51.2) and 10.8% (3.4, 29.8), respectively. The sensitivity of Cor a 1-sIgE (60.2% [46.9, 72.2]) was lower than for hazelnut extract-sIgE (95.7% [88.7, 98.5]), while their specificities did not differ significantly. CONCLUSION: sIgE to Cor a 14 and Cor a 9 hazelnut storage proteins increases diagnostic specificity in assessing hazelnut allergy in children. The combined use of hazelnut extract and hazelnut storage proteins may improve diagnostic value.

12.
Curr Opin Urol ; 30(2): 245-250, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31834082

RESUMO

PURPOSE OF REVIEW: Approximately 30% of clinical stage 1 (CS1) nonseminomatous germ cell tumours (NSGCT) and 15-20% of CS1 seminoma relapse without adjuvant treatment. Despite this, the 5-year survival for CS1 is 99%. The purpose of this review is to assess if active surveillance should be standard for all patients with CS1 testis cancer independent of risk factors. RECENT FINDINGS: Recent data from Princess Margaret Cancer Centre suggest a nonrisk-adapted surveillance approach avoids treatment in ∼70% of patients. Most relapse early at a median time of 7.4 months. The majority of relapses are confined to the retroperitoneum (66%) and only one modality of treatment is required: chemotherapy only in 61% and RPLND only in 73%. SUMMARY: Surveillance is the preferred option and a safe proven strategy for the management of CS1 disease independent of risk factors. The prognosis for CS1 disease is excellent and the decision to offer surveillance or adjuvant treatment needs to highlight the treatment-related morbidity in an otherwise fit and healthy young man.

13.
Pediatr Cardiol ; 41(2): 407-413, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31853581

RESUMO

To analyze the prevalence, types, and risk factors for cardiac arrhythmias associated with peripherally inserted central catheters (PICCs) in children. This is a case-control single center retrospective study. From 3180 PICCs inserted in children (< 18 years old) between 2009 and 2013, cases with new onset arrhythmias were identified. Demographics, type and timing of arrhythmias, and possible risk factors were analyzed. ECGs, rhythm strips, physicians' records, and anti-arrhythmic management were confirmatory. The level of the PICC's tip in the superior vena cava (SVC) or right atrium (RA) was ascertained from chest X-rays and counted in rib units (RU) and vertebra units (VU). Cases were matched (1:1 ratio) to controls by weight and date of insertion. Descriptive statistics were performed. A two-sided p value < 0.05 was considered significant. Thirty-one children (1%) developed arrhythmias, 16/31 (56%) were males, and 24/31 (77%) were < 1-year age. Arrhythmias were atrial 22 (71%), ventricular 4 (13%), and undetermined 5 (16%). Median PICC dwell time was 16 days. 14/31 (45%) cases and 9/31 (29%) controls had underlying structural heart disease. PICCs central tip position was lower among cases than controls (RU 6 vs 5). Odds Ratio for developing arrhythmia was 4.5 (95% CI 0.98-20.83) if the tip lays below 6.25RU. Arrhythmias were resolved with anti-arrhythmic agents in 52% (16/31) and with PICC exchange/manipulation in 32% (10/31) cases. Two children died unrelated to arrhythmia. Prevalence of arrhythmias associated with PICCs in children is low (1%). Arrhythmias are 4.5 times more likely when PICC's central tip position is deeper than 6.25RU.

15.
Cells ; 8(12)2019 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-31847394

RESUMO

Liquid biopsy-based biomarkers, such as microRNAs, represent valuable tools for patient management, but often do not make it to integration in the clinic. We aim to explore issues impeding this transition, in the setting of germ cell tumors, for which novel biomarkers are needed. We describe a model for identifying and validating clinically relevant microRNAs for germ cell tumor patients, using both in vitro, in vivo (mouse model) and patient-derived data. Initial wide screening of candidate microRNAs is performed, followed by targeted profiling of potentially relevant biomarkers. We demonstrate the relevance of appropriate (negative) controls, experimental conditions (proliferation), and issues related to sample origin (serum, plasma, cerebral spinal fluid) and pre-analytical variables (hemolysis, contaminants, temperature), all of which could interfere with liquid biopsy-based studies and their conclusions. Finally, we show the value of our identification model in a specific scenario, contradicting the presumed role of miR-375 as marker of teratoma histology in liquid biopsy setting. Our findings indicate other putative microRNAs (miR-885-5p, miR-448 and miR-197-3p) fulfilling this clinical need. The identification model is informative to identify the best candidate microRNAs to pursue in a clinical setting.

16.
BJU Int ; 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31863617

RESUMO

OBJECTIVES: To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT). PATIENTS AND METHODS: A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes. RESULTS: In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high-intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T-stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow-up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR-free survival (hazard ratio 6.624, 95% confidence interval 2.243-19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5-9.5) and 23.5 (15.75-25) respectively, while in the final follow-up the median (IQR) values were 7 (3.5-11) and 6 (5-12.25), respectively (P = 0.088 and P < 0.001). At last follow-up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter. CONCLUSIONS: sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31872899

RESUMO

BACKGROUND: Peanut allergy diagnosis relies on clinical reactivity to peanut supported by detection of specific IgE (sIgE) antibodies. Extract-based sIgE tests have low specificity, so component-resolved diagnostics may complement whole-extract testing. METHODS: We systematically collected peanut allergen component data in seven databases and studied the diagnostic accuracy of peanut storage proteins (Arah1, 2, 3) and cross-reactive peanut proteins (Arah8 PR-10 and Arah9 lipid transfer protein) through meta-analyses. The systematic literature review included studies employing peanut components and oral food challenge (OFC) as reference standard in patients suspected of peanut allergy. Data for component sIgE at pre-defined detection thresholds were extracted and combined in random-effects bivariate meta-analyses. Risk of bias was assessed as recommended by Cochrane, with two additional quality items of importance for this review. RESULTS: Nineteen eligible studies presented data suitable for meta-analysis. In cross-sectional pediatric studies, the pooled sensitivity of Arah2-sIgE at 0.35 kUA /L cutoff was 83.3% [95% CI 75.6, 88.9] and specificity in diagnosing objective peanut allergy was 83.6% [95% CI 77.4, 88.4]. Compared with 0.1 and 1.0 kUA /L, this threshold provided the best diagnostic accuracy. At 0.35 kUA /L, Arah1 and Arah3 had comparable specificity (86.0% and 88.0%, respectively) but significantly lower sensitivity compared with Arah2 (37.0% and 39.1%, respectively; P < .05). CONCLUSION: sIgE to Arah2 can enhance the certainty of diagnosis and reduce the number of OFC necessary to rule out clinical peanut allergy in unclear cases.

18.
Front Neurol ; 10: 1072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681147

RESUMO

Transcranial Doppler (TCD) ultrasound has been demonstrated to be a valuable tool for assessing cerebral hemodynamics via measurement of cerebral blood flow velocity (CBFV), with a number of established clinical indications. However, CBFV waveform analysis depends on reliable pulse onset detection, an inherently difficult task for CBFV signals acquired via TCD. We study the application of a new algorithm for CBFV pulse segmentation, which locates pulse onsets in a sequential manner using a moving difference filter and adaptive thresholding. The test data set used in this study consists of 92,012 annotated CBFV pulses, whose quality is representative of real world data. On this test set, the algorithm achieves a true positive rate of 99.998% (2 false negatives), positive predictive value of 99.998% (2 false positives), and mean temporal offset error of 6.10 ± 4.75 ms. We do note that in this context, the way in which true positives, false positives, and false negatives are defined caries some nuance, so care should be taken when drawing comparisons to other algorithms. Additionally, we find that 97.8% and 99.5% of onsets are detected within 10 and 30 ms, respectively, of the true onsets. The algorithm's performance in spite of the large degree of variation in signal quality and waveform morphology present in the test data suggests that it may serve as a valuable tool for the accurate and reliable identification of CBFV pulse onsets in neurocritical care settings.

19.
Can Urol Assoc J ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31702544

RESUMO

INTRODUCTION: The management of advanced prostate cancer (PCa) continues to evolve with the emergence of new diagnostic and therapeutic strategies. As a result, there are multiple areas in this landscape with a lack of high-level evidence to guide practice. Consensus initiatives are an approach to establishing practice guidance in areas where evidence is unclear. We conducted a Canadian-based consensus forum to address key controversial areas in the management of advanced PCa. METHODS: As part of a modified Delphi process, a core scientific group of PCa physicians (n=8) identified controversial areas for discussion and developed an initial set of questions, which were then reviewed and finalized with a larger group of 29 multidisciplinary PCa specialists. The main areas of focus were non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), oligometastatic prostate cancer, genetic testing in prostate cancer, and imaging in advanced prostate cancer. The predetermined threshold for consensus was set at 74% (agreement from 20 of 27 participating physicians). RESULTS: Consensus participants included uro-oncologists (n=13), medical oncologists (n=10), and radiation oncologists (n=4). Of the 64 questions, consensus was reached in 30 questions (n=5 unanimously). Consensus was more common for questions related to biochemical recurrence, sequencing of therapies, and mCRPC. CONCLUSIONS: A Canadian consensus forum in PCa identified areas of agreement in nearly 50% of questions discussed. Areas of variability may represent opportunities for further research, education, and sharing of best practices. These findings reinforce the value of multidisciplinary consensus initiatives to optimize patient care.

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