Nationwide Network Research Articles

Training for transformation: examining food systems courses at US land-grant universities

Higher education institutions can play an essential role in preparing students to participate in movements for just and sustainable food systems change. For the past two decades, many United States land-grant universities (LGUs) have developed food systems education (FSE) courses. This study examined the extent to which FSE courses employ four capacities deemed crucial by the FSE literature: multidimensional approaches, interdisciplinarity, centering equity, and training students to take action in food systems. The syllabi of 171 undergraduate courses at 20 LGUs were obtained by contacting instructors, and their course descriptions and learning outcomes were analyzed. This subset of LGUs were identified from the membership list of the Menus of Change University Research Collaborative (MCURC), a nationwide network of colleges using campus dining halls and classrooms as living laboratories for food systems change. Most course descriptions and learning outcomes exhibited multidimensional approaches and interdisciplinarity. However, many failed to incorporate teaching content and practices that help students critically examine equity and social justice issues in food systems, or engage in transformative change. LGUs have both the resources and urgent responsibility to empower students to be part of movements to transform unjust, unsustainable food systems. The findings of this study, and an accompanying open-access syllabus website, aim to accelerate the development of FSE curricula that prepare students to change food systems.

Cohort profile: a nationwide study in Dutch CHEK2 c.1100delC families using the infrastructure of the HEreditary Breast and Ovarian cancer study Netherlands – Hebon-CHEK2

PurposeCHEK2 c.1100delC is associated with an increased breast cancer risk in women. While this variant is prevalent in the Netherlands (1% in the general population), knowledge of aetiology and prognosis...

Enabling patients with health-related social needs.

183 Background: Addressing health-related social needs (HRSNs) is essential to help ensure patients surviving cancer achieve optimal outcomes. Socioeconomic and environmental insecurities can make it challenging for patients to successfully complete their treatments. The US Oncology Network (The Network), has partnered with Findhelp, a resource facilitation tool enabling anyone with internet access to connect with community-based organizations providing discounted or free social services to meet resource needs. This alliance enables an enhanced level of assistance for patients in need, supporting optimal outcomes for those disadvantaged by various circumstances, such as HRSNs impacted by social drivers of health (SDoH). Methods: Beginning April 25 th , 2024, patients utilizing Navigating Cancer’s patient portal, across 302 community-based oncology clinics serving nearly 500,000 patients annually, could access information through a Findhelp website unique to practices in The Network. The investigators are collecting engagement data based on click rates to the Findhelp website link via the patient portal, the number of unique visitors to The Network’s Findhelp application, and the county, city, and zip code of users accessing the application. Data from the Findhelp website will be assessed to determine which insecurity categories (i.e. food, housing, goods, transit, health, money, care, education, work, legal) and areas across the nationwide network of practices receive the highest engagement, and if there is variability based on subgroup analyses. The subgroup analyses will be performed based on patient demographics and include age, gender, race, and geographic location. Results: Initial retrospective results from this prospective study reveals the average number of searches by patients prior to go-live was 106/day. Post go-live averages have been 4,369/day, a 4,037% uplift in engagement. Top searched needs have been health (26.5%), food (22.3%), and housing (21.1%). Additional data elements are being derived from aggregated, de-identified patient engagement and search activity by geographic location categorized by resource insecurity. Conclusions: Conclusions are being drawn based on outcome measures and cross walking with search and referral activities. The goal of the collaboration is to increase awareness of technologies and local organizations within communities bridging the resource gap by way of facilitating services through the Findhelp platform; ultimately empowering patients to overcome health-related social needs and barriers to care leading to improved access.

Two is better than one: Let's get married!

AbstractMarriage provides a key insight to American life. Marriage is a significant factor when analyzing our society and our current structure – a widening gap among social classes. The decline in marriages among middle and lower class reflects issues with education attainment and financial stability. Unfortunately, there has been no initiative to address the declining marriage rate. This Note proposes a two‐alternative approach to implementing family‐friendly policies and a nationwide network of Family Centers that will aid the current and next generation. Society will obtain a more educated, cooperative workforce, with a more stable family structure across all classes.

Mycosis Fungoides and Associated Malignancies in a Dutch Nationwide Retrospective Cohort Study.

The prognosis of patients with mycosis fungoides is variable. As the current literature is scarce and shows mixed results this study investigates the incidence of other primary malignancies in mycosis fungoides patients. A retrospective, nationwide, population- based cohort study was performed with patients with mycosis fungoides between 2000 and 2020 in The Netherlands. All histopathology reports were requested from the Nationwide Network and Registry of Histo- and Cytopathology and screened for other primary malignancies. Lifelong incidence rates were used to compare the incidence of malignancies in mycosis fungoides patients and the general population. In total 1,024 patients were included with a mean follow-up of 10 years (SD 6). A total of 294 cases of other primary malignancies were found with 29% of the mycosis fungoides patients developing at least 1 other primary malignancy. Only cutaneous (odds ratio [OR] 2.54; CI 2.0-3.2) and haematological malignancies (OR 2.62; CI 2.00-3.42) had a statistically significant higher incidence than the Dutch population overall. Mycosis fungoides patients have a significantly increased risk of developing melanomas (OR 2.76; CI 2.11-3.59) and cutaneous squamous cell carcinomas mycosis fungoides (OR 2.34; CI 1.58-3.45). This study shows no association between mycosis fungoides and other solid organ tumours; however, such patients are significantly at risk of developing other haematological and cutaneous malignancies. Clinicians should be aware of this increased risk.

Phylo-geo haplotype network-based characterization of SARS-CoV-2 strains circulating in India (2020-2022).

Background & objectives Genetic analysis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains circulating in India during 2020-2022 was carried out to understand the evolution of potentially expanding and divergent clades. Methods SARS-CoV-2 sequences (n=612) randomly selected from among the sequences of samples collected through a nationwide network of Virus Research Diagnostic Laboratories during 2020 (n=1532) and Indian sequences available in Global Initiative on Sharing All Influenza Data during March 2020-March 2022 (n=53077), were analyzed using the phylo-geo haplotype network approach with reference to the Wuhan prototype sequence. Results On haplotype analysis, 420 haplotypes were revealed from 643 segregating sites among the sequences. Haplotype sharing was noted among the strains from different geographical regions. Nevertheless, the genetic distance among the viral haplotypes from different clades could differentiate the strains into distinct haplo groups regarding variant emergence. Interpretation & conclusions The haplotype analysis revealed that the G and GR clades were co-evolved and an epicentrefor the evolution of the GH, GK and GRA clades. GH was more frequently identified in northern parts of India than in other parts, whereas GK was detected less in north India than in other parts. Thus, the network analysis facilitated a detailed illustration of the pathways of evolution and circulation of SARS-CoV-2 variants.

Abstract Introduction

Abstract The 6th Kidney Cancer Research Summit (KCRS) took place on July 11th & 12th, 2024 as a hybrid event both in Boston, Massachusetts at the InterContinental Boston, and virtually via Zoom webinar. The conference format consists of oral presentations in an intimate setting that enables dynamic discussion among attendees. The meeting began with a keynote titled “How the Air We Breathe Can Impact Cancer,” showing the biological processes underlying how airborne microparticles drive inflammatory processes that fuel tumorigenesis. Sessions included Exploring Novel Drug Targets for RCC, Novel Imaging and Biomarkers to Guide RCC Patient Management, State of the Science, Trials in Progress, Clinical and Scientific Updates in Kidney Cancer, Immunotherapy Advances and Research, Oral Abstracts, and Rapid Abstracts. The KCRS was inaugurated in 2019 to congregate the community of researchers conducting projects involving kidney cancer with clinicians, industry partners, and patient advocates in order to foster new collaborations and generate constructive feedback. KCRS is funded through sponsors, partnerships, and grassroots supporters organized by KidneyCAN, a nationwide network of kidney cancer patients, caregivers, and family members who are committed to accelerating cures for kidney cancer. Basic through translational and clinical research are included, and the program is centered on projects funded through the Department of Defense’s Kidney Cancer Research Program awards. The goal is to give current and future projects the best chance to succeed and ensure the orientation of goals towards raising the standard of care and improving patient outcomes across all histological subtypes and stages of this disease. This supplement contains a complete list of scheduled abstract presentations that were accepted as of June 17th, 2024. Please be aware that some abstracts may have been withdrawn or rescheduled at the authors’ request.

Emergency response and preparedness among Polish human milk banks: a comparison of the COVID-19 pandemic and the 2022 Ukrainian refugee crisis.

In recent years, Poland has faced two major emergencies: the COVID-19 pandemic, a global-scale public health emergency in 2020, and the outbreak of a full-scale war in Ukraine, which forced over 9 million Ukrainians-mostly women and children-to flee from their country through the Polish-Ukrainian border in 2022. In 2020 and 2022, we conducted two online questionnaires with human milk bank personnel to assess the impact of these emergencies on the human milk banking sector and its preparedness to face them. All 16 human milk bank entities operating in Poland were contacted and invited to participate in the study. For the first questionnaire, which was distributed in 2020, we obtained a 100% response rate. For the second questionnaire, the response rate was 88%, i.e., 14 out of 16 human milk banks completed the questionnaire. We compared these two emergencies in terms of the extent to which the potential of the Polish human milk bank network was exploited to support vulnerable infants who were not breastfed. Our findings indicate that recommendations to provide donor human milk to infants separated from their mothers during the COVID-19 pandemic were never fully implemented. Meanwhile, during the refugee crisis, national legislation allowing equal access to public healthcare for Ukrainian citizens were rapidly implemented, enabling a more effective response by human milk banks to support vulnerable infants. However, no specific measures were introduced to support refugees outside the standard criteria for donor human milk provision. Our results highlight the limited response from the sector during emergencies and the underutilization of the potential of a nationwide network of professional human milk banks. Drawing on Polish experiences, we emphasize the importance of having procedures and legal regulations regarding human milk banking in place even in non-crisis settings, which would facilitate a rapid emergency response. We also emphasize the need to include the implementation of emergency procedures in building a strong and resilient human milk banking system.

Poverty Governance in the Delegated Welfare State: Privatization, Commodification, and the U.S. Health Care Safety Net

Abstract Due to forces of retrenchment and fiscal austerity in the contemporary U.S. welfare state, the federal government has increasingly delegated the funding of public programs to private entities. How does privatization influence the way marginalized populations experience the social safety net? To develop insights on delegated poverty governance, this study examines a longstanding public-private program—Federally Qualified Health Centers (FQHCs)—which comprise a nationwide network of clinics serving over thirty million predominantly low-income patients in medically underserved areas. I conducted a case study drawing on in-depth interviews with patients and staff in a small-town FQHC in the Rust Belt. Unlike other social welfare programs, I found a pronounced absence of stigma associated with the FQHC, largely due to features of the delegated policy design, the blended institutional setting, and strategic organizational decisions. However, low-income patients were also unaware of their rights to treatment when encountering paternalistic enforcement of overdue billing rules, which resulted in delayed or foregone health care. Due to underlying tensions surrounding commodification, I argue that privatization of the safety net may quell the stigma of government programs among the poor while simultaneously disentitling individuals from their rights of social citizenship.

Implementation and Evaluation of a National Multidisciplinary Kidney Genetics Clinic Network Over 10 Years

IntroductionDiagnostic genomic sequencing is the emerging standard of care in nephrology. There is a growing need to scale up the implementation of genomic diagnostics nationally to improve patient outcomes. MethodsThis pragmatic study provided genomic or genetic testing to patients with suspected monogenic kidney disease through a national network of kidney genetics clinics. We sought to evaluate the experiences of implementing genomic diagnostics across Australia and associated diagnostic outcomes between 2013 and 2022. ResultsWe successfully established and expanded a nationwide network of 20 clinics as of 2022, concurrently developing laboratory, research, and education programs to scale the clinical application of genomics in nephrology. We report on an Australian cohort of 1,506 kidney patients, of whom 1,322 received their test results. We assessed barriers to implementation in the nephrology context and, where possible, applied real-time solutions to improve clinical processes over ten years. ConclusionDeveloping a multidisciplinary kidney genetics model across multiple health services nationally was highly successful. This model supported optimal care of individuals with monogenic kidney disease in an economically responsible way. It has continued to evolve with technological and service developments and is now set to scale further as genomic testing for kidney patients transitions to healthcare system funding.

Diamond Gymnura natalensis and duckbill Aetomylaeus bovinus rays undertake nationwide coastal migrations.

Migration is a critical aspect of ocean ecosystems, and understanding this phenomenon answers ecological and management questions. Given the difficulty in tracking ocean animals across large distances, the extent to which different ray species perform long-distance movements, such as migrations, remains unknown. This study used passive acoustic telemetry to track the movements of endemic diamond Gymnura natalensis and critically endangered duckbill Aetomylaeus bovinus rays along the South African coastline using a collaborative nationwide network of coastal acoustic receivers for up to 7 years. Duckbill rays were detected significantly more frequently than diamond rays, but both species moved between the south and east coasts of South Africa (traveling up to 1167 km). Tagged individuals were detected significantly more often in their tagging locations during summer months but traveled significantly further distances during winter months. Furthermore, movement models fitted to individual duckbill rays' annual net-squared displacement identified most individual annual movements as migratory. This evidence suggests that both diamond and duckbill rays make eastward winter migrations and return to specific areas along the coastline during the summer months. The exceptions to this were diamond rays tagged on the east coast that were not found to migrate seasonally, which supports previous research that there is intraspecific variability in migrations for ray species. These findings have implications for understanding ray migration not only on a global scale but also locally for spatial management interventions and population delineation.

Raising the Bar for Real-World Data in Oncology: Approaches to Quality Across Multiple Dimensions.

Electronic health record (EHR)-based real-world data (RWD) are integral to oncology research, and understanding fitness for use is critical for data users. Complexity of data sources and curation methods necessitate transparency into how quality is approached. We describe the application of data quality dimensions in curating EHR-derived oncology RWD. A targeted review was conducted to summarize data quality dimensions in frameworks published by the European Medicines Agency, The National Institute for Healthcare and Excellence, US Food and Drug Administration, Duke-Margolis Center for Health Policy, and Patient-Centered Outcomes Research Institute. We then characterized quality processes applied to curation of Flatiron Health RWD, which originate from EHRs of a nationwide network of academic and community cancer clinics, across the summarized quality dimensions. The primary quality dimensions across frameworks were relevance (including subdimensions of availability, sufficiency, and representativeness) and reliability (including subdimensions of accuracy, completeness, provenance, and timeliness). Flatiron Health RWD quality processes were aligned to each dimension. Relevancy to broad or specific use cases is optimized through data set size and variable breadth and depth. Accuracy is addressed using validation approaches, such as comparison with external or internal reference standards or indirect benchmarking, and verification checks for conformance, consistency, and plausibility, selected on the basis of feasibility and criticality of the variable to the intended use case. Completeness is assessed against expected source documentation; provenance by recording data transformation, management procedures, and auditable metadata; and timeliness by setting refresh frequency to minimize data lags. Development of high-quality, scaled, EHR-based RWD requires integration of systematic processes across the data lifecycle. Approaches to quality are optimized through knowledge of data sources, curation processes, and use case needs. By addressing quality dimensions from published frameworks, Flatiron Health RWD enable transparency in determining fitness for real-world evidence generation.

League of VetaHumanz SuperPower Pack Program: Introducing Young People from Diverse Backgrounds to STEM Learning Activities and Veterinary Science Careers.

League of VetaHumanz uses a nationwide network of university-community partnerships to provide veterinary STEM learning experiences for children who are more likely to lack access to enriching, supplemental educational opportunities due to systemic barriers based on their race, ethnicity, or socioeconomic status. To include participation beyond in-person programming, SuperPower Packs, self-guided, learning experiences, were developed. Leveraging social cognitive career theory and the "Batman Effect," SuperPower Packs are designed to build self-efficacy, and seed STEM and veterinary science career aspirations by engaging children in STEM learning through connections with a veterinary role model. Four SuperPower Packs were developed. Beginning in the fall of 2021, for 17 months, 16,655 SuperPower Packs were distributed to children in 23 states. A small portion of children who received the game (3.8%, N = 614, 6-12 years old) returned evaluation surveys that measured activity engagement, likelihood of role model identification and demographics. Participants indicated variation in their experiences, but mean scale scores show desirable perceptions of engagement (MRange = 2.38 - 2.90/3) and role model identification (MRange = 2.15 - 2.94/3). These positive learning and role model experiences help set the stage to encourage youth to pursue similar learning and career opportunities in the future.

Impact of Thyroid Status on Incident Kidney Dysfunction and Chronic Kidney Disease Progression in a Nationally Representative Cohort

ObjectiveTo examine the relationship between thyroid status and incident kidney dysfunction/chronic kidney disease (CKD) progression. Patients and MethodsWe examined incident thyroid status, ascertained by serum thyrotropin (TSH) levels measured from January 1, 2007, through December 31, 2018, among 4,152,830 patients from the Optum Labs Data Warehouse, containing deidentified retrospective administrative claims data from a large national health insurance plan and electronic health record data from a nationwide network of provider groups. Associations of thyroid status, categorized as hypothyroidism, euthyroidism, or hyperthyroidism (TSH levels >5.0, 0.5-5.0, and <0.5 mIU/L, respectively), with the composite end point of incident kidney dysfunction in patients without baseline kidney dysfunction and CKD progression in those with baseline CKD were examined using Cox models. ResultsPatients with hypothyroidism and hyperthyroidism had higher risk of incident kidney dysfunction/CKD progression in expanded case-mix analyses (reference: euthyroidism): adjusted hazard ratios (aHRs) (95% CIs) were 1.37 (1.34 to 1.40) and 1.42 (1.39 to 1.45), respectively. Incrementally higher TSH levels in the upper reference range and TSH ranges for subclinical, mild overt, and overt hypothyroidism (≥3.0-5.0, >5.0-10.0, >10.0-20.0, and >20.0 mIU/L, respectively) were associated with increasingly higher risk of the composite end point (reference: TSH level, 0.5 to <3.0 mIU/L): aHRs (95% CIs) were 1.10 (1.09 to 1.11), 1.37 (1.34 to 1.40), 1.70 (1.59 to 1.83), and 1.70 (1.50 to 1.93), respectively. Incrementally lower TSH levels in the subclinical (<0.5 mIU/L) and overt (<0.1 mIU/L) hyperthyroid ranges were also associated with the composite end point: aHRs (95% CIs) were 1.44 (1.41 to 1.47) and 1.48 (1.39 to 1.59), respectively. ConclusionIn a national cohort, TSH levels in the upper reference range or higher (≥3.0 mIU/L) and below the reference range (<0.5 mIU/L) were associated with incident kidney dysfunction/CKD progression.

Self-reported characteristics of people seeking primary care physiotherapy in Denmark: A cross-sectional study.

Limited knowledge exists on the self-reported characteristics of patients seeking primary care physiotherapy in Denmark. To describe primary symptom site, co-occurrent pain sites, pain intensity, symptom duration, and number of symptom episodes in patients seeking primary care physiotherapy using patient-reported data. Cross-sectional study of patients seeking primary care physiotherapy within a nationwide network of clinics in Denmark (FysioDanmark® ). Data from the FysioDanmark® clinical database with patient-reported information obtained from questionnaires distributed to patients prior to their first consultation were used. This included primary symptom site, co-occurrent pain sites, pain intensity (0-10 numeric rating scale), symptom duration, and number of symptom episodes. Data from 61,097 patients (57% female) aged 42years (interquartile range 29-53) and 63,566 first visits were included. The most common reasons for seeking care were back- (22.9%), non-specific- (19.8%) and shoulder symptoms (15.9%). The majority of patients (89.4%) reported symptoms lasting longer than 7days, and many experienced recurrent episodes. Median pain intensity ranged from 3 to 5 across primary symptom sites and age groups. In general, females reported higher pain intensity than males. Danish patients seeking primary care physiotherapy most commonly presented with back, non-specific, and shoulder symptoms, with mild-to-moderate pain lasting longer than 7days, and many with recurrent episodes.

Effectiveness of multimodal participant recruitment in SPARK, a large, online longitudinal research study of autism.

SPARK launched in 2016 to build a US cohort of autistic individuals and their family members. Enrollment includes online consent to share data and optional consent to provide saliva for genomic analysis. SPARK's recruitment strategies include social media and support of a nation-wide network of clinical sites. This study evaluates SPARK's recruitment strategies to enroll a core study population. Individuals who joined between January 31, 2018, and May 29, 2019 were included in the analysis. Data include sociodemographic characteristics, clinical site referral, the website URL used to join, how the participant heard about SPARK, enrollment completion (online registration, study consents, and returning saliva sample), and completion of the baseline questionnaire. Logistic regressions were performed to evaluate the odds of core participant status (completing enrollment and baseline questionnaire) by recruitment strategy. In total, 31,715 individuals joined during the study period, including 40% through a clinical site. Overall, 88% completed online registration, 46% returned saliva, and 38% were core participants. Those referred by a clinical site were almost twice as likely to be core participants. Those who directly visited the SPARK website or performed a Google search were more likely to be core participants than those who joined through social media. Being a core participant may be associated with the "personal" connection and support provided by a clinical site and/or site staff, as well as greater motivation to seek research opportunities. Findings from this study underscore the value of adopting a multimodal recruitment approach that combines social media and a physical presence.

Sociodemographic Inequities in Telemedicine Use Among US Patients Initiating Treatment in Community Cancer Centers During the Ongoing COVID-19 Pandemic, 2020-2022.

Although telemedicine was seen as a way to improve cancer care during the coronavirus disease (COVID-19) pandemic, there is limited information regarding inequities in its uptake. This study assessed sociodemographic factors associated with telemedicine use among patients initiating treatment for 20 common cancers. This retrospective cohort study used deidentified electronic health record-derived patient data from a nationwide network of community cancer practices, linked to area-level Census information. We included adults (age 18 years and older) who initiated first-line systemic cancer treatment between March 2020 and December 2022 (follow-up through March 2023). Exposures include race/ethnicity, insurance status, and area-level social determinants of health (eg, block group socioeconomic status [SES]). The outcome was telemedicine use within 90 days after treatment initiation. Associations were examined using logistic regression models adjusted for age, sex, performance status, stage, and cancer type. This study included 36,993 patients (48.6% women; median age, 69 years), of whom 15.1% used telemedicine services. Black (12.2%; odds ratio [OR], 0.78 [95% CI, 0.70 to 0.88]) and uninsured (9.2%; OR, 0.59 [95% CI, 0.48 to 0.73]) patients were less likely to use telemedicine services than their White and well-insured counterparts (14.5% and 15.0%, respectively). Patients in rural (9.7%; OR, 0.54 [95% CI, 0.46 to 0.57]), suburban (11.8%; OR, 0.67 [95% CI, 0.61 to 0.74]), and low SES areas (9.9%; OR, 0.39 [95% CI, 0.35 to 0.43]) were less also likely to use telemedicine than their counterparts in urban (16.6%) or high SES (21.6%) areas. Nearly one sixth of patients initiating cancer treatment during the pandemic used telemedicine, but there were substantial inequities. The proliferation of telemedicine may perpetuate cancer care inequities if marginalized populations do not have equitable access.

Ongoing attempts towards decolonising a British D.Clin.Psy. research space

In this article, a summary is provided of certain actions towards decolonising the research space within a British D.Clin.Psy. programme, and some of the thinking that informed these actions. The importance of decolonisation in universities, and in clinical psychology – despite the ‘challenges’ that it seems to pose to some - is discussed. Genuine efforts towards decolonisation are rendered distinct from more general equality, diversity and inclusion activities - unlike ‘diversification’, decolonisation demands systemic changes in spaces, such that colonising / recolonising functions cease to operate. It is noted that some British D.Clin.Psy. programmes have made concrete steps towards decolonisation; and in complementing such initiatives, and also in drawing inspiration from experiences and perspectives from elsewhere in the world, some actions towards decolonisation in Plymouth University’s D.Clin. Psy. programme’s research space have been initiated. These have included recognising, challenging and providing alternatives to the Western and Eurocentric models that have dominated how we have traditionally thought and taught about, and conducted research in, clinical psychology; communicating the importance of recognising the adoption of the Western ‘scientific method’ as a deliberate epistemological and ontological choice; and, actively supporting the undertaking of social justice and community-orientated research by D.Clin.Psy. trainees. In the interests of collaboration and mutual support, a suggestion is made to establish a nationwide network devoted to the meaningful decolonisation of clinical psychology in the UK.

Japanese carnivorous plant groups and organisations

The 13th ICPS International Conference, held in Himeji City, Japan, in May 2023, was supported by a nation-wide network of carnivorous plant groups and organisations in Japan.

Performance and Interlaboratory Reproducibility of Droplet Digital Polymerase Chain Reaction (ddPCR) and Real Time PCR for KIT D816V Mutation Detection: A Nationwide Pilot Study By the RIMA (Rete Italiana Mastocitosi) Association

Systemic Mastocytosis (SM) is a rare hematological neoplasm, but its incidence is probably underestimated because of the heterogeneity of clinical symptoms and presentation that may cause diagnostic difficulties especially outside reference centers. Detection of the activating D816V KIT mutation in the bone marrow or peripheral blood is one of the minor criteria for the diagnosis of SM, but it poses some challenges since in the indolent forms (the most frequent) the mast cell burden is very low. For this reason, the National Comprehensive Cancer Network and the European Competence Network on Mastocytosis (ECNM) recommend a high-sensitivity PCR-based assay, such as Allele-Specific Oligonucleotide-Real Time Quantitative PCR (ASO-qPCR) or ddPCR, while Sanger and Next Generation Sequencing are considered not adequate. Accurate quantitation of allele burden (AB) is also desirable since it offers diagnostic (an AB³10% qualifies as a B-finding according to the latest WHO classification) and prognostic information and might be used to monitor response to tyrosine kinase inhibitors. Despite the widespread routine availability of real time and digital PCR technologies, a map of labs across Italy offering KIT D816V testing with adequate sensitivity is lacking, nor have cooperative efforts aimed to check lab performance and reproducibility of diagnostic results ever been performed. Based on these premises, RIMA undertook, with the sponsorship of the GIMEMA Working Party on Chronic Myeloproliferative Neoplasms, a project aimed to: i) build a nationwide network of competent reference laboratories performing KIT D816V mutation testing; ii) promote harmonization of local procedures and ensure adequate proficiency and cross-comparability of results. The pilot phase of this project involved 7 labs (L) spread across the country (Milan, Bologna, Verona, Florence, Rome, Naples, Pavia) serving one or more reference clinical centers for the diagnosis and management of SM. First, a survey aimed to assess the techniques and procedures in use in each participating lab was conducted. Five labs (L2-L6) used a commercial ddPCR assay (KIT p.D816V c.2447A&amp;gt;T, Assay ID dHsaCP2000023; Bio-Rad); one lab (L7) used a home brew ASO-qPCR assay; one lab (L1) used a commercial semi-quantitative real time PCR-based assay (PlentiPlex Mastocytosis D816V kit; Pentabase). All labs performed analyses in duplicate or triplicate using DNA as input material, with amounts variable from 50 to 250ng/replicate. Reported limit of detection (LoD) was 0.0003% for the home brew method and 0.01% for the commercial methods. Subsequently, a round robin test to evaluate and compare performance in terms of sensitivity and inter-lab reproducibility was carried out. Mutated and wild-type DNA isolated from HMC-1.2 and HL-60 cells, respectively, was mixed and diluted to mimic different D816V ABs, from 10% down to 0.01%. Dilutions were externally assessed by the UK Wessex Genomics Laboratory Service, using an accredited ddPCR assay with a limit of detection (LoD) of 0.01%. Of note, the sixth dilution (D6) was scored as slightly below their LoD (0.008%; 3 positive droplets only). Identical batches of blinded vials were then distributed and analyzed in parallel by the 7 participating labs according to their own routine protocols. Positivity/negativity as scored by L1-7 and AB values as scored by L2-7 are detailed in Table 1. All the evaluated methods proved highly accurate in the detection and, for ddPCR and ASO-qPCR, in the quantitation of the KIT D816V (R 2 between 0.988 and 0.998). A very high degree of concordance was achieved, for all dilutions, across different labs and methods (CV between 0.07 and 0.8). D6 was scored borderline by L1 and positive by all other labs. This pilot experience demonstrates that the evaluated PCR-based methods may reliably identify and quantitate the KIT D816V mutation down to an AB of 0.01% with a high degree of cross-comparability of results, thus assisting clinicians in the diagnosis and monitoring of SM patients. To the best of our knowledge, this is the first cooperative effort aimed to assess the performance and reproducibility of KIT D816V mutation testing in SM. Involvement of additional Italian labs is already planned, and further implementation within the ECNM will be proposed. Definition of common SOPs, uniform sample requirements and web-based reporting following the GIMEMA LabNet model will be pursued.