Hereditary transthyretin-mediated amyloidosis with polyneuropathy: baseline anthropometric, demographic and disease characteristics of patients from a reference center

ABSTRACT Background: Hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy is a rare, inherited, multisystem, and often fatal disease caused by a variant in transthyretin (TTR) gene. Baseline characteristics of patients, especially anthropometric data, are scarce in the literature, and they are relevant to define effective treatment strategies. Objective: This study aimed to describe baseline demographic, anthropometric, and disease characteristics in a cohort of patients from a reference center in Brazil. Methods: Symptomatic patients not previously included in clinical trials and eligible for treatment were enrolled. Ethnicity, state of residence, age, sex, weight, height, body mass index (BMI), TTR variant, and Polyneuropathy Disability Score (PND) at diagnosis were analyzed. Results: Among the 108 patients enrolled, 58.33% were male, 60.19% were Caucasian, and 83.33% lived in the Southeast region. Mean age was 51.61 (±16.37) years, mean weight was 65.76 (±15.16) kg, mean height was 168.33 (±10.26) cm, and mean BMI was 23.11 (±4.45) kg/m2. The most prevalent variant was V30M (86.11%). Patients with PND score 0 presenting autonomic neuropathy were 14.81%. Patients with PND score I-II and III-IV were 52.78 and 32.41%, respectively. Mean weight and BMI were significantly lower in patients with sensory-motor manifestations. Conclusions: This is the largest cohort of patients in Brazil for whom anthropometric characteristics have been described. Baseline demographic, anthropometric, and disease data indicate that delay in diagnosis of hATTR amyloidosis with polyneuropathy is still a problem and that efforts must be made to expedite diagnosis and maximize opportunities for new disease-modifying treatments.

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P403 Post hoc examination of VISIBLE 1 data for baseline predictors of response to 2 or 3 IV doses of vedolizumab for adults with moderate-to-severe ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.532 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S372-S373

Author(s):

W Sandborn ◽

E V Loftus ◽

F Baert ◽

J Jansson ◽

J Chen ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Severe Ulcerative Colitis ◽

Mayo Score ◽

Disease Characteristics ◽

Predictors Of Response ◽

Baseline Characteristics ◽

Post Hoc ◽

Disease Location ◽

Baseline Demographic

Abstract Background Vedolizumab (VDZ) is a gut-selective α 4β 7 integrin monoclonal antibody approved for IV administration for moderate to severe ulcerative colitis (UC). The phase 3 VISIBLE 1 study evaluated SC VDZ for UC maintenance therapy. After 2 IV doses, 56.1% patients had a clinical response at week 6; among patients who received a third induction infusion, clinical response rates were 79.7%. In this post hoc analysis, we examined baseline characteristics as predictors of clinical response to IV induction with VDZ. Methods In the VISIBLE 1 study (NCT02611830; EudraCT 2015-000480-14), patients (patients) received IV VDZ 300 mg at Weeks 0 and 2. At Week 6, clinical responders were randomised to maintenance SC therapy; nonresponders were given a third IV dose and reassessed at Week 14. As endoscopy was only available at Week 6, the clinical response at Week 6 was defined as ≥3 points and ≥30% reduction in complete Mayo score from Week 0 and at Week 14 as a ≥2 points and ≥25% reduction in partial Mayo score from Week 0. Both definitions also included an accompanying decrease in rectal bleeding subscore ≥1 or absolute subscore ≤1. Results Overall, 383 patients received ≥1 dose of IV VDZ. Of these, 56.1% responded at Week 6 after 2 VDZ doses. Of the 143 patients who received 3 IV doses, 79.7% responded at Week 14. No clinically meaningful differences in baseline demographic and disease characteristics were observed between patients who responded after 2 or 3 IV doses (Table). Differences in disease location and partial Mayo score (< or ≥6) were observed between the responders and nonresponders in the 3 IV dose group. Baseline characteristics were evaluated descriptively to assess predictors of clinical response after 2 or 3 IV VDZ doses. Conclusion Clinical response was achieved by most patients after either 2 or 3 IV VDZ infusions in the VISIBLE 1 trial. Post hoc analyses revealed no clinically meaningful differences in baseline characteristics or disease characteristics that could serve as predictors of response following 2 or 3 VDZ infusions. Further real-world experience may elucidate potential predictors of response to VDZ.

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Validity of Recreational Marathon Runners’ Self-Reported Anthropometric Data

Perceptual and Motor Skills ◽

10.1177/0031512520930159 ◽

2020 ◽

Vol 127 (6) ◽

pp. 1068-1078

Author(s):

Pantelis T. Nikolaidis ◽

Beat Knechtle

Keyword(s):

Body Mass ◽

Assessment Method ◽

Fat Percentage ◽

Anthropometric Data ◽

Anthropometric Measures ◽

Marathon Runners ◽

Present Sample ◽

Large Samples ◽

Anthropometric Characteristics ◽

Recreational Runners

While studies on large samples of recreational runners have often relied on participants’ self-reported height and body mass, the validity of these data have not been investigated for this population. Hence, this study sought to examine the validity of self-reported anthropometric measures among recreational marathon runners. Female ( n = 32) and male ( n = 135) recreational marathon runners were requested to estimate their body mass and height (and we calculated their self-reported body mass index [BMI]), after which we took actual measures of their body mass and height and calculated their actual BMI. Participants’ self-reported values underestimated their actual body mass by 0.65 kg ( p < .001, η2 = 0.222) and their actual BMI by 0.35 kg ⋅ m−2 ( p < .001, η2 = 0.245). There was a significant Assessment Method × Sex Interaction for both body mass ( p = .019, η2 = 0.033) and BMI ( p = .017, η2 = 0.034), as women underestimated body mass values more than men. Participants overestimated their height by 0.44 cm ( p < .001, η2 = 0.075), but the interaction of sex and assessment method for height was not statistically significant. Underestimates of body mass correlated with marathon racing speed ( r = .24, p = .006) and body fat percentage ( r = −.29, p = .001) in men, but not in women ( p > .05). The disagreement between self-reported and measured anthropometric data in the present sample was lower than has been previously reported for the general population, suggesting that marathon runners may more accurately self-perceive and/or report their anthropometric characteristics. These findings are of practical value for health professionals and researchers (e.g., nutritionists and exercise physiologists) questionnaires to recreational marathon runners.

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Tazemetostat (TAZ) in relapsed/refractory (R/R) follicular lymphoma (FL): Propensity-score matched analysis of E7438-G000-101 trial outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18627 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18627-e18627

Author(s):

David Proudman ◽

Deepshekhar Gupta ◽

Dave Nellesen ◽

Alex Wong ◽

Jay Yang ◽

...

Keyword(s):

Propensity Score ◽

Single Agent ◽

Objective Response ◽

Prior History ◽

Cell Transplant ◽

Phase 2 ◽

Matched Sample ◽

Hematopoietic Stem ◽

Disease Characteristics ◽

Baseline Characteristics

e18627 Background: Oncology drug development often requires the use of non-randomized, open-label, phase 2 basket studies to better understand the early activity and safety of a potential new therapy. As such, baseline demographics and disease characteristics may differ between cohorts which can impact the perception of efficacy between cohorts. TAZ, a first-in-class, oral enhancer of zeste homolog 2 (EZH2) inhibitor was approved by the US FDA after demonstrating single-agent, antitumor activity in a phase 2 study in adults with wild-type (WT) or mutant (MT) EZH2 R/R FL who had received ≥2 prior systemic therapies (NCT01897571). Differences between the cohorts in baseline characteristics known to be prognostic for clinical outcomes were noted, with the WT EZH2 cohort enrolling more patients with poor-risk features. This analysis assessed outcomes in the 2 groups after minimizing differences in baseline characteristics by creating a matched sample of directly comparable WT and MT patients. Methods: Propensity scores for each WT (n = 54) and MT (n = 45) EZH2 patient in the study were generated, based on the likelihood of being selected given their baseline characteristics. Characteristics identified for inclusion in the model were chosen if they were prognostic based on peer-reviewed literature and where larger differences were observed between cohorts at baseline: ECOG performance status, number of prior lines of anticancer therapy, progression of disease within 24 months, double refractory status, and prior history of hematopoietic stem cell transplant. Patients were matched 1:1 on propensity score, using a nearest-neighbor approach with caliper restrictions. Baseline covariates between the two matched groups were found to be sufficiently balanced. Objective response rate (ORR) point estimates were measured for the matched WT and MT EZH2 groups, and progression-free survival (PFS) was described using Kaplan-Meier analyses. Results: The propensity-matched sample included 56 patients (28 WT and 28 MT). Prior to matching, ORR was 35% (95% CI [22%, 48%]) in the WT and 69% (95% CI [55%, 83%]) in MT EZH2 groups; after matching, the ORR was 50% (95% CI [31%, 69%]) and 71% (95% CI [54%, 88%]), respectively. Median PFS was 11.1 months (95% CI [5.4, 16.7]) in the WT and 13.8 months (95% CI [11.1, 22.1]) in the MT EZH2 groups prior to matching, and 14.3 months (95% CI [11.1, inf]) and 14.8 (95% CI [10.7, inf]) months in the WT and MT EZH2 matched groups, respectively. Conclusions: As expected, efficacy remained higher in the MT EZH2 group; however, after adjustment, the ORR and PFS improved in the WT EZH2 group. This hypothesis-generating analysis suggests that outcomes in patients with WT EZH2 R/R FL treated with TAZ may have been more similar to those in the MT EZH2 group in the phase 2 trial had the baseline disease characteristics been more equally matched.

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Diphtheria: the patch remains

The Journal of Laryngology & Otology ◽

10.1258/002221503770716250 ◽

2003 ◽

Vol 117 (10) ◽

pp. 807-810 ◽

Cited By ~ 11

Author(s):

Raj Nandi ◽

Mriganka De ◽

Simon Browning ◽

Prabhati Purkayastha ◽

A. K. Bhattacharjee

Keyword(s):

Early Diagnosis ◽

Respiratory Tract ◽

Respiratory Distress ◽

Retrospective Analysis ◽

Fatal Disease ◽

Disease Characteristics ◽

Intravenous Antibiotics ◽

Number Of Patients ◽

History Of ◽

Clinical Records

This study analysed the number of patients admitted with diphtheria to a teaching hospital in the state of Assam in India over a period of five years and compared the disease characteristics and management with outcomes and incidences of diphtheria reported in the literature. It was a retrospective analysis of data elicited from clinical records of patients admitted to hospital.A total of 101 admissions were recorded during a five-year period between March 1997 to March 2002, mostly with pharyngeal diphtheria (90 per cent). The majority of patients had no history of immunization (70 per cent). Significant presenting features were a tonsillar patch, sore throat, respiratory distress and fever. All patients were treated with anti-diphtheritic serum and intravenous antibiotics. Steroids were given to 81 per cent of patients and tracheostomy was carried out in 10 per cent of cases. The mortality was 16 per cent.Diphtheria of the respiratory tract remains a potentially fatal disease commonly presenting with membranous pharyngitis. Early diagnosis and treatment with anti-diphtheritic serum and antibiotics remain the cornerstone of treatment. Inadequate immunization cover is deemed responsible for the continued menace of diphtheria.

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Health-related Physical Fitness in Older Adult Europeans: The IN COMMON SPORT Study

10.21203/rs.3.rs-153079/v1 ◽

2021 ◽

Author(s):

Jose M Cancela ◽

Irimia Mollinedo-Cardalda ◽

Manuela Ferreira ◽

Pedro Bezerra

Keyword(s):

Physical Fitness ◽

Lower Limb ◽

Senior Citizens ◽

Eastern European ◽

Anthropometric Data ◽

Hand Grip ◽

Lower Limb Strength ◽

Anthropometric Characteristics ◽

Health Related ◽

European Group

Abstract Background This comparative descriptive study analysed the physical fitness and the anthropometric data of senior citizens participating in "IN COMMON SPORTS" project, in accordance with their place of residence. MethodsA total of 418 participants divided into two groups: Eastern European Group (EEG) and Southern European Group (SEG). Each participants' anthropometric characteristics (body mass index, body fat and waist hip ratio) and fitness (Senior Fitness Test and Hand grip) were studied. Results The Subjects from the SEG showed significantly lower anthropometric values than those from the EEG. The SEG subjects presented significant differences in physical fitness, with best values for upper and lower limb strength and aerobic resistance, while those from the EEG presented significantly better values for lower limb flexibility. Conclusion Senior citizens aged 60+ years present differences in physical fitness in accordance with their country of residence; the Southern Europeans having the best physical fitness.

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How Do Head and Neck Cancer Patients Prioritize Treatment Outcomes Before Initiating Treatment?

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.4.877 ◽

2000 ◽

Vol 18 (4) ◽

pp. 877-877 ◽

Cited By ~ 126

Author(s):

Marcy A. List ◽

John Stracks ◽

Laura Colangelo ◽

Pamela Butler ◽

Natasha Ganzenko ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Treatment Effects ◽

Performance Status ◽

Treatment Strategies ◽

Individual Variability ◽

Lower Priority ◽

Disease Characteristics

PURPOSE: To determine, pretreatment, how head and neck cancer (HNC) patients prioritize potential treatment effects in relationship to each other and to survival and to ascertain whether patients’ preferences are related to demographic or disease characteristics, performance status, or quality of life (QOL). PATIENTS AND METHODS: One hundred thirty-one patients were assessed pretreatment using standardized measures of QOL (Functional Assessment of Cancer Therapy-Head and Neck) and performance (Performance Status Scale for Head and Neck Cancer). Patients were also asked to rank a series of 12 potential HNC treatment effects. RESULTS: Being cured was ranked top priority by 75% of patients; another 18% ranked it second or third. Living as long as possible and having no pain were placed in the top three by 56% and 35% of patients, respectively. Items that were ranked in the top three by 10% to 24% of patients included those related to energy, swallowing, voice, and appearance. Items related to chewing, being understood, tasting, and dry mouth were placed in the top three by less than 10% of patients. Excluding the top three rankings, there was considerable variability in ratings. Rankings were generally unrelated to patient or disease characteristics, with the exception that cure and living were of slightly lower priority and pain of higher priority to older patients compared with younger patients. CONCLUSION: The data suggest that, at least pretreatment, survival is of primary importance to patients, supporting the development of aggressive treatment strategies. In addition, results highlight individual variability and warn against making assumptions about patients’ attitudes vis-à-vis potential outcomes. Whether patients’ priorities will change as they experience late effects is currently under investigation.

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Impact of Changing Treatment Strategies on Outcomes in Pediatric Ulcerative Colitis

Inflammatory Bowel Diseases ◽

10.1093/ibd/izz072 ◽

2019 ◽

Vol 25 (11) ◽

pp. 1838-1844 ◽

Cited By ~ 5

Author(s):

Rishi Bolia ◽

Jeremy Rajanayagam ◽

Winita Hardikar ◽

George Alex

Keyword(s):

Ulcerative Colitis ◽

Hospital Admissions ◽

Treatment Strategies ◽

Median Number ◽

Cumulative Probability ◽

Therapeutic Drug ◽

Disease Outcomes ◽

Group 2 ◽

Group 1 ◽

Baseline Demographic

Abstract Background In recent years, treatment strategies for ulcerative colitis have evolved with an early step-up approach, the availability of biologicals, and therapeutic drug monitoring. We carried out this study to evaluate the effect of these changes on disease outcomes. Methods In this retrospective review, 2 time periods were defined: Group 1 (2005–2010) and Group 2 (2011–2016). Baseline demographic, endoscopic parameters, and medication use were compared. Overall colectomy rate, number of disease flares per year, and number of hospital admissions per year were compared between the 2 groups. Results Group 1 had 71 children, and in children in Group 2. The use of 5-ASA increased in Group 2 (Group 2, 99.2% vs. Group 1, 84.5%, P = 0.0007). In addition, infliximab and thiopurines were introduced earlier in the disease course. The 2-year cumulative probability of colectomy decreased from 14% to 3% (P = 0.02) between the 2 periods. No change in median number of flares per year [Group 1, 0.41 (IQR 0.6) vs. Group 2, 0.62 (IQR 0.91), P = 0.28] or median number of hospital admissions per year [Group 1, 0.30 (IQR 0.77) vs. Group 2, 0.21 (IQR 0.75), P = 0.52] was seen. Thereafter, we proceeded to identify the changes in treatment strategies that were responsible for the reduction in colectomy and we found that the use of infliximab OR 3.7 (95% CI 1.1–11.7), P = 0.02, was independently associated with it. Conclusions A reduction in 2-year colectomy rates has been observed in patients with pediatric ulcerative colitis since biologics have become available for its treatment. The numbers of disease-flares rates and hospital admissions remain unchanged.

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P3628Contemporary coronary artery disease prevalence in a valvular heart disease population undergoing surgery

European Heart Journal ◽

10.1093/eurheartj/ehz745.0486 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T J Carvalho Mendonca ◽

C Strong ◽

D Roque ◽

L Morais ◽

J P Reis ◽

...

Keyword(s):

Coronary Artery ◽

Treatment Strategies ◽

Disease Prevalence ◽

Valve Surgery ◽

Heart Valve Surgery ◽

Left Main ◽

All Cause Mortality ◽

Baseline Characteristics ◽

Artery Disease

Abstract Background Patients undergoing heart valve surgery are routinely evaluated for the presence of Coronary Artery Disease (CAD), with the standard practice of combining valve intervention with a revascularization procedure, notably Coronary Artery Bypass Graft (CABG). Older studies suggest rates as high as 50% prevalence of CAD in this population. However, CAD prevalence, its treatment and prognostic implication has been questioned recently. Objectives The goal of this study is to evaluate the baseline characteristics, prevalence of CAD and treatment strategies in a contemporary population with valvular heart disease (VHD) referred for valve surgery. Methods In a national multicentre registry, consecutive patients, from Jan 2015 to Dec 2016, with a formal indication for heart valve surgery referred for a pre-op routine coronary angiogram were systematically analysed. Baseline characteristics, valve pathology and CAD prevalence and patterns were determined. Obstructive CAD was defined as luminal angiographic stenosis ≥70% (≥50% for left main artery). The prognostic impact of the different valve disease and CAD treatment strategies were assessed. Results 1175 patients (mean age 72.5±10.1; male 49.2%) fulfilled the clinical or echocardiographic indication for valve surgery by European guidelines. Valvular disease prevalence was: aortic stenosis (66.7%), aortic regurgitation (6.6%), mitral stenosis (6%), mitral regurgitation (19.2%), tricuspid regurgitation (7.5%). Mean follow-up time was 29.06±18.46 months. Prevalence of comorbidities was: Diabetes Mellitus (DM) 26%, chronic obstructive pulmonary disease (COPD) 5.7% and chronic kidney disease (CKD) 23.4%. Mean Euroscore II was 2.6%. Obstructive CAD was present in 27.3% patients. Mean Syntax score was 10.2 (<22 in 88%, 23–32 in 10.2% and >33 in 1.8%). Left main artery and 3-vessel disease were found in 13.1% and 11.8% of patients with CAD, respectively. Valvular surgery was ultimately performed in 80.3%. In patients with CAD, 57.3% were revascularized. All-cause mortality rate during follow-up was 12.9%, with 7.8% from cardiovascular causes. In univariate analysis DM, COPD, CKD, NYHA class, obstructive CAD and no surgery (p<0.05) were associate with mortality on follow up. In multivariate analysis obstructive CAD (OR 2.36, 95% CI 1.53–3.65, p<0.01) and no surgery (OR 6.05, 95% CI 3.95–9.30, p<0.01) persisted as independent all-cause mortality predictors. Conclusion In a contemporary cohort of patients with VHD and surgical indication, CAD prevalence is lower (27.3%) than described in literature. Mortality rates were higher in patients with obstructive CAD, worse NYHA functional class and in those who never underwent surgery.

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Necrotizing Enterocolitis Incidence, Characteristics, and Outcomes in Neonatal Down Syndrome Patients

American Journal of Perinatology ◽

10.1055/s-0037-1603688 ◽

2017 ◽

Vol 34 (13) ◽

pp. 1368-1374

Author(s):

Urbee Haque ◽

Yongjie Miao ◽

Carl Backes ◽

Clifford Cua

Keyword(s):

Down Syndrome ◽

Necrotizing Enterocolitis ◽

Demographic Data ◽

Ductus Arteriosus ◽

Term Infants ◽

Obstructive Lesion ◽

Medical Issues ◽

Increased Risk ◽

Baseline Characteristics ◽

Baseline Demographic

Introduction Neonates with Down syndrome (nDS) have multiple medical issues that may place them at an increased risk of necrotizing enterocolitis (NEC). The goal of this study was to determine the incidence, characteristics, and outcomes of nDS patients that developed NEC. Methods Data from the Pediatric Health Information Systems database on all nDS were reviewed. Demographics, medical conditions, development of NEC, and mortality were recorded. Patients were divided into nDS patients who developed NEC (nDS-NEC) versus nDS patients who did not develop NEC (nDS-nNEC). Results Incidence of NEC in nDS patients was 6.6% (381/5,737). Baseline demographic data indicated nDS-NEC patients were more likely to be born earlier, have a diagnosis of congenital diaphragmatic hernia, ventricular septal defect, patent ductus arteriosus, Ebstein's anomaly, or a left-sided obstructive lesion versus nDS-nNEC patients. The odds ratio for death in the nDS-NEC patients was 2.5 (95% confidence interval, 1.8–3.3) versus the nDS-NEC patients. Conclusion The incidence of NEC in nDS patients requiring admission to a children's hospital after birth is much higher than that reported for term infants. Baseline characteristics differ in nDS patients that may place them at a higher risk for NEC. nDS-NEC patients have an increased morbidity and a significantly higher mortality compared with the nDS-nNEC patients.

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Characterization of Wnt signaling pathway (WSP) aberrations in advanced prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.203 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 203-203

Author(s):

Fady Ghali ◽

Devin Patel ◽

Christina Jamieson ◽

J Kellogg Parsons ◽

Rana R. McKay

Keyword(s):

Prostate Cancer ◽

Wnt Signaling ◽

Signaling Pathway ◽

De Novo ◽

Wnt Signaling Pathway ◽

Treatment Strategies ◽

Activating Mutations ◽

Disease Characteristics ◽

Activating Mutation ◽

Visceral Metastases

203 Background: Aberrations in Wnt signaling pathway (WSP) are implicated in disease progression and resistance of multiple malignancies including prostate cancer (PCa). We sought to characterize the clinical phenotype and molecular genotype of PCa patients with WSP alterations. Methods: Eligible patients included those with PCa having undergone clinical-grade next generation DNA sequencing of tumor derived from prostate or metastasis tissue. We identified patients with somatic activating mutations in CTNNB1 and RSPO2, or inactivating mutations in APC, RNF43, or ZNRF3. Patient and disease characteristics were collected. Clinical and outcome parameters were associated with WSP mutation status using STATA(V. 13.1, College Station, Texas). Results: A total of 169 patients were identified of whom 29 (18.1%) had a WSP activating mutation. Median age of the overall cohort was 64.85 (IQR 56.77, 70.36). 115 (68.0%) patients had Gleason 8-10 disease, 34 (20.1%) presented with de novo metastatic disease, 85 (50.3%) developed CRPC and 23 (13.6%) developed visceral metastases. Clinical characteristics were similar between biomarker groups. There was no association with the presence of a Wnt activating mutation and RB1, p53, pTEN, or BRCA1/2 alteration. Median time to CRPC was 39.42 (IQR 14.50 – 87.52) and 24.39 (IQR 14.99 – 46.03) months for no-WSP and WSP-aberrant respectively. Median 5-year OS was 83.7% (95% CI 73.0-90.4%) and 79.6% (95% CI 52.9 – 92.2%) months for no-WSP and WSP-aberrant respectively. Table evaluates biomarker status with time to CRPC development and overall survival (OS). Conclusions: We observe that somatic WSP activating mutations are present in 18.1% of patients with mPCa, consist with prior reports. Understanding the clinical significance of WSP alterations is critical to inform treatment strategies in patients with advanced disease.[Table: see text]

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