Making Sense of Censored Covariates: Statistical Methods for Studies of Huntington's Disease.

The landscape of survival analysis is constantly being revolutionized to answer biomedical challenges, most recently the statistical challenge of censored covariates rather than outcomes. There are many promising strategies to tackle censored covariates, including weighting, imputation, maximum likelihood, and Bayesian methods. Still, this is a relatively fresh area of research, different from the areas of censored outcomes (i.e., survival analysis) or missing covariates. In this review, we discuss the unique statistical challenges encountered when handling censored covariates and provide an in-depth review of existing methods designed to address those challenges. We emphasize each method's relative strengths and weaknesses, providing recommendations to help investigators pinpoint the best approach to handling censored covariates in their data.

Reporting Minority Race and Ethnicity in Cardiovascular and Thoracic Journals.

INTRODUCTION: Currently, there is no mandatory standard for reporting race and ethnicity in medical journals, presenting significant barriers to studying disparities in medical outcomes. We seek to investigate whether greater recent awareness of diversity and inclusion reflects in reporting of race and ethnicity by peer-reviewed cardiothoracic articles. METHODS: Pubmed was queried for clinical outcomes articles published from January 2017 to June 2023 in the Journal of Thoracic and Cardiovascular Surgery, Annals of Thoracic Surgery, Journal of Heart and Lung Transplantation, and CHEST Journal. Basic science, translational studies, and international studies were excluded. SAS Studio was used for statistical analysis. RESULTS: 817 papers were reviewed, 378 reported race/ethnicity with 354 (93%) reporting White, 267 (71%) reporting Black, 128 (34%) reporting Hispanic, and 119 (31%) reporting Asian. Over 8-y, there were no statistically significant changes in percent of articles that included White (odds ratio 0.808 95% confidence interval [0.624-1.047], P = 0.1068), Black (1.125 [0.984-1.288], P = 0.0857), or Asian (1.096 [0.960-1.250], P = 0.1751) groups. Hispanics were more likely to be reported in recent years (1.147 [1.006-1.307], P = 0.0397). Subset analysis was performed on cardiac (n = 157) and thoracic articles (n = 157) with no significant trends for race reporting in these subsets. CONCLUSIONS: Minorities remain underrepresented in reported patient populations in peer-reviewed cardiothoracic journals. Future efforts should prioritize accurately representing these populations in the literature. Inaccurate data and exclusion of minority populations can contribute to disparities observed in overall outcomes.

A single-cell atlas deconstructs heterogeneity across multiple models in murine traumatic brain injury and identifies novel cell-specific targets.

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution. We identify cell-specific targets and previously unrecognized roles for microglial and ependymal subtypes. Ependymal-4 was a hub of neuroinflammatory signaling. A distinct microglial lineage shared features with disease-associated microglia at 24 h, with persistent gene-expression changes in microglia-4 even 6 months after contusional TBI, contrasting all other cell types that mostly returned to naive levels. Regional and sexual dimorphism were noted. CEREBRI, our searchable atlas (https://shiny.crc.pitt.edu/cerebri/), identifies previously unrecognized cell subtypes/molecular targets and is a leverageable platform for future efforts in TBI and other diseases with overlapping pathophysiology.

Comparative osseointegration of hydrophobic tissue-level tapered implants-A preclinical in vivo study.

PURPOSE: To histometrically compare the osseointegration and crestal bone healing of a novel tapered, self-cutting tissue-level test implant with a standard tissue-level control implant in a submerged healing regimen. MATERIALS AND METHODS: In a mandibular minipig model, implants were inserted and evaluated histometrically after a healing period of 3, 6, and 12 weeks. The primary outcome was the evaluation of bone-to-implant contact (BIC) and secondary outcomes were primary stability as per insertion torque and first BIC (fBIC). Outcomes for the test and control implants were compared using Wilcoxon signed-rank tests and mixed linear regression models. RESULTS: Insertion torque values were significantly higher for the test (50.0 ± 26.4 Ncm) compared to the control implants (35.2 ± 19.7 Ncm, p = .0071). BIC values of test implants were non-inferior to those of control implants over the investigated study period. After 12 weeks, the corresponding values measured were 81.62 ± 11.12% and 90.41 ± 4.81% (p = .1763) for test and control implants, respectively. Similarly, no statistical difference was found for fBIC values, except for the 12 weeks outcome that showed statistically lower values for the test (-675.58 ± 590.88 µm) compared to control implants (-182.75 ± 197.40 µm, p = .0068). CONCLUSIONS: Novel self-cutting tissue-level implants demonstrated noninferior osseointegration and crestal bone height maintenance to the tissue-level implants. Histometric outcomes between both implants demonstrated test implants were statistically noninferior to control implants, despite substantial differences in the bone engagement mechanism and resulting differences in insertion torque and qualitative bone healing patterns.

Entanglement Kinetics in Polymer Melts Are Chemically Specific.

We investigate the universality of entanglement kinetics in polymer melts. We compare predictions of a recently developed constitutive equation for disentanglement to molecular dynamics simulations of both united-atom polyethylene and Kremer-Grest models for polymers in shear and extensional flow. We confirm that entanglements recover on the retraction time scale, rather than the reptation time scale. We find that the convective constraint release parameter ß is independent of molecular weight, but that it increases with the ratio of Kuhn length bK to packing length p as ß âˆ¼ (bK/p)α, with an exponent α = 1.9, which may suggest that disentanglement rate correlates with an increase in the tube diameter. These results may help shed light on which polymers are more likely to undergo shear banding.

Guided internet-based LGBTQ-affirmative cognitive-behavioral therapy: A randomized controlled trial among sexual minority men in China.

OBJECTIVE: LGBTQ-affirmative cognitive-behavioral therapy (CBT) addresses minority stress to improve sexual minority individuals' mental and behavioral health. This treatment has never been tested in high-stigma contexts like China using online delivery. METHOD: Chinese young sexual minority men (n = 120; ages 16-30; HIV-negative; reporting depression and/or anxiety symptoms and past-90-day HIV-transmission-risk behavior), were randomized to receive 10 sessions of culturally adapted asynchronous LGBTQ-affirmative internet-based CBT (ICBT) or weekly assessments only. The primary outcome included HIV-transmission-risk behavior (i.e., past-30-day condomless anal sex). Secondary outcomes included HIV social-cognitive mechanisms (e.g., condom use self-efficacy), mental health (e.g., depression), and behavioral health (e.g., alcohol use), as well as minority stress (e.g., acceptance concerns), and universal (e.g., emotion regulation) mechanisms at baseline and 4- and 8-month follow-up. Moderation analyses examined treatment efficacy as a function of baseline stigma experiences and session completion. RESULTS: Compared to assessment only, LGBTQ-affirmative ICBT did not yield greater reductions in HIV-transmission-risk behavior or social-cognitive mechanisms. However, LGBTQ-affirmative ICBT yielded greater improvements in depression (d = -0.50, d = -0.63) and anxiety (d = -0.51, d = -0.49) at 4- and 8-month follow-up, respectively; alcohol use (d = -0.40) at 8-month follow-up; and certain minority stress (e.g., internalized stigma) and universal (i.e., emotion dysregulation) mechanisms compared to assessment only. LGBTQ-affirmative ICBT was more efficacious for reducing HIV-transmission-risk behavior for participants with lower internalized stigma (d = 0.42). Greater session completion predicted greater reductions in suicidality and rumination. CONCLUSIONS: LGBTQ-affirmative ICBT demonstrates preliminary efficacy for Chinese young sexual minority men. Findings can inform future interventions for young sexual minority men in contexts with limited affirmative supports.

Development of an intervention for patients following an anterior cruciate ligament rupture: an online nominal group technique consensus study.

OBJECTIVES: (1) To develop an intervention for to support patients diagnosed with an anterior cruciate ligament (ACL) rupture with decision-making regarding treatment. (2) To define evidence-based recommendations for the treatment of patients following an ACL rupture. DESIGN: Nominal group technique consensus study. SETTING: Online meetings with patients and key stakeholders working and receiving treatment in the National Health Service, UK. PARTICIPANTS: Consensus meetings composed of eight voting participants and five non-voting facilitators. Voting participants included five clinicians, one outpatient therapy manager and two patients with experience in an ACL rupture and reconstructive surgery. Non-voting facilitators supported group discussions and/or observed study procedures. This included a clinical academic expert, two methodology experts and two patient representatives. METHOD: Two online meetings were held. Pre-elicitation material was distributed ahead of the first meeting. Premeeting voting was conducted ahead of both meetings. A draft of the shared decision-making intervention and recommendations were shared ahead of the second meeting. Components were discussed and ranked for inclusion based on a 70% agreement threshold. RESULTS: The meetings led to the development of a shared decision-making intervention to support treatment decision-making following an ACL rupture. The intervention includes two components: (1) a patient information leaflet and key questions diagram and (2) option grid. The evidence-based recommendations encompass core components of treatment reaching the 70% threshold agreed by the group. The recommendations cover: (1) advice and education, (2) exercise guidance, (3) intervention delivery, (4) outcome measure use and (5) shared decision-making. CONCLUSION: This study has successfully developed a shared decision-making intervention to support ACL treatment decision-making, ready for testing in a future feasibility study. Evidence-based recommendations for the treatment of patients following ACL injury, ready for testing in a National Health Service (UK) setting, are also presented. TRIAL REGISTRATION NUMBER: NCT05529511.

The Role of Immunotherapy in the Management of Esophageal Cancer in Patients Treated with Neoadjuvant Chemoradiation: An Analysis of the National Cancer Database.

BACKGROUND: The current National Comprehensive Cancer Network advises neoadjuvant chemoradiotherapy followed by surgery for locally advanced cases of esophageal cancer. The role of immunotherapy in this context is under heavy investigation. METHODS: Patients with esophageal adenocarcinoma were identified in the National Cancer Database (NCDB) from 2004 to 2019. Three groups were generated as follows: (a) no immunotherapy, (b) neoadjuvant immunotherapy, and (c) adjuvant immunotherapy. Overall survival was evaluated using the Kaplan-Meier method and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality. RESULTS: Of the total 14,244 patients diagnosed with esophageal adenocarcinoma who received neoadjuvant chemoradiation, 14,065 patients did not receive immunotherapy, 110 received neoadjuvant immunotherapy, and 69 received adjuvant immunotherapy. When adjusting for established risk factors, adjuvant immunotherapy was associated with significantly improved survival compared to no immunotherapy and neoadjuvant immunotherapy during a median follow-up period of 35.2 months. No difference was noted among patients who received no immunotherapy vs. neoadjuvant immunotherapy in the same model. CONCLUSIONS: In this retrospective analysis of the NCDB, receiving adjuvant immunotherapy offered a significant survival advantage compared to no immunotherapy and neoadjuvant immunotherapy in the treatment of esophageal adenocarcinoma. The addition of neoadjuvant immunotherapy to patients treated with neoadjuvant chemoradiation did not improve survival in this cohort. Further studies are warranted to investigate the long-term outcomes of immunotherapy in esophageal cancer.

Stable isotopes reveal trophic ontogeny in Cisco (Coregonus artedi).

Cisco (Coregonus artedi) are a widespread, cold-water zooplanktivore native to North America. Although Cisco are generally referred to as an "obligate zooplanktivore," there is some evidence that the species exhibits considerable variability in trophic niche. Here, we assessed how Cisco body size relates to trophic position, that is, trophic ontogeny. We analysed 13C and 15N isotopes from Cisco ranging from 127 to 271 mm in body length (n = 66) from Trout Lake, Vilas County, Wisconsin, USA. 15N isotopes showed smaller Cisco had a trophic position of ~3, which steadily increased to ~3.5 for larger Cisco. Further, 13C isotope signatures showed Cisco transitioned to be more pelagically reliant (lower 13C signatures). Using gillnet catch data, we found that larger Cisco were using deeper habitats than smaller Cisco. Our results support that Cisco have significant variability in trophic niche even though they are traditionally thought of as an obligate planktivore. Overall, we emphasize that researchers should be cautious when generalizing Cisco trophic function, particularly when considering the broader food web.

Phosphonodiamidate prodrugs of phosphoantigens (ProPAgens) exhibit potent Vγ9/Vδ2 T cell activation and eradication of cancer cells.

The phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) is an established activator of Vγ9/Vδ2 T cells and stimulates downstream effector functions including cytotoxicity and cytokine production. In order to improve its drug-like properties, we herein report the design, synthesis, serum stability, in vitro metabolism, and biological evaluation of a new class of symmetrical phosphonodiamidate prodrugs of methylene and difluoromethylene monophosphonate derivatives of HMBPP. These prodrugs, termed phosphonodiamidate ProPAgens, were synthesized in good yields, exhibited excellent serum stability (>7 h), and their in vitro metabolism was shown to be initiated by carboxypeptidase Y. These phosphonodiamidate ProPAgens triggered potent activation of Vγ9/Vδ2 T cells, which translated into efficient Vγ9/Vδ2 T cell-mediated eradication of bladder cancer cells in vitro. Together, these findings showcase the potential of these phosphonodiamidate ProPAgens as Vγ9/Vδ2 T cell modulators that could be further developed as novel cancer immunotherapeutic agents.

Psychosocial Impact of Penile Cancer: An Unmet Need.

Penile cancer is a rare cancer, where patients not only need to deal with the anxiety around a cancer diagnosis, but also manage the consequences of treatment on their self-esteem, body image, and intimate relationships. Many find it embarrassing and difficult to talk to family and friends. Due to this, changes in urination and other physical effects of treatment, many will withdraw from social activities too. Patients need psychosocial support and more needs to be done to address this unmet need. Holistic and multidisciplinary approaches in clinic, with access to counseling, may help patients adjust to their new situation.

High-Throughput In Vivo Screening Identifies Differential Influences on mRNA Lipid Nanoparticle Immune Cell Delivery by Administration Route.

Immune modulation through the intracellular delivery of nucleoside-modified mRNA to immune cells is an attractive approach for in vivo immunoengineering, with applications in infectious disease, cancer immunotherapy, and beyond. Lipid nanoparticles (LNPs) have come to the fore as a promising nucleic acid delivery platform, but LNP design criteria remain poorly defined, making the rate-limiting step for LNP discovery the screening process. In this study, we employed high-throughput in vivo LNP screening based on molecular barcoding to investigate the influence of LNP composition on immune tropism with applications in vaccines and systemic immunotherapies. Screening a large LNP library under both intramuscular (i.m.) and intravenous (i.v.) injection, we observed differential influences on LNP uptake by immune populations across the two administration routes, gleaning insight into LNP design criteria for in vivo immunoengineering. In validation studies, the lead LNP formulation for i.m. administration demonstrated substantial mRNA translation in the spleen and draining lymph nodes with a more favorable biodistribution profile than LNPs formulated with the clinical standard ionizable lipid DLin-MC3-DMA (MC3). The lead LNP formulations for i.v. administration displayed potent immune transfection in the spleen and peripheral blood, with one lead LNP demonstrating substantial transfection of splenic dendritic cells and another inducing substantial transfection of circulating monocytes. Altogether, the immunotropic LNPs identified by high-throughput in vivo screening demonstrated significant promise for both locally- and systemically-delivered mRNA and confirmed the value of the LNP design criteria gleaned from our screening process, which could potentially inform future endeavors in mRNA vaccine and immunotherapy applications.

Pedunculated Osteochondroma Presenting as Verruca Vulgaris: A Diagnosis Requiring a High Index of Suspicion: Case Report.

Introduction: Osteochondromas are the most common benign tumors of the bone and can be sessile or pedunculated. Although osteochondromas are typically seen in the long bones, they are rarely seen in the small bones of the hand or foot. Verruca vulgaris, also known as the common wart, is one of the most common skin conditions presenting to physicians and must be distinguished either clinically or histologically from other hyperkeratotic conditions, including bone conditions such as bone tumors that can place pressure on the skin and cause callus formation that can mimic a wart or create skin deformity. A high index of suspicion for underlying bone mass or tumor should be entertained when evaluating patients for skin conditions, particularly of the hand or foot, with failure to improve with treatment. Case Report: This case report presents a 20-year-old male with a pedunculated osteochondroma of the left fourth distal phalanx with hyperkeratotic skin overlying the mass at the end of the toe. He was initially treated by a family doctor and podiatrist for verruca vulgaris for over 5 years with two treatments of liquid nitrogen cryotherapy and surgical excision of the mass when the treating podiatrist encountered bone and recommended radiographs. The family requested follow-up with our practice several days later after they were told the patient had a bone tumor. The patient requested surgical excision of the osteochondroma secondary to pain with activities and difficulties with his vocation as a pilot. Conclusion: All physicians must be mindful of an underlying bone tumor or mass in patients presenting with skin changes, particularly about the foot or hand. Knowledge that an underlying bone tumor can present as a verruca vulgaris may prevent a delay in diagnosis or unnecessary treatment when evaluating and treating a patient with a skin lesion. Fortunately, our case was a benign osteochondroma; a malignant tumor with a delay in diagnosis could lead to loss of limb or life.

Delayed gangrenous penile necrosis following prolonged utilization of penile constriction ring.

Penile strangulation secondary to utilization of a constrictive ring is a rare urologic emergency that requires urgent decompression to prevent prolonged vascular obstruction resulting in necrosis and gangrene. Current literature is mainly comprised of case presentations that focus on management in the acute setting via removal of the ring. Herein, we describe surgical management of a patient who presents in delayed fashion after self-removal of the constrictive ring. We discuss our penectomy-sparing technique of debridement and split thickness skin graft.

A Transplant-Inclusive Value-Based Kidney Care Payment Model.

In the United States, kidney care payment models are migrating toward value-based care (VBC) models incentivizing quality of care at lower cost. Current kidney VBC models will continue through 2026. We propose a future transplant-inclusive VBC (TIVBC) model designed to supplement current models focusing on patients with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD). The proposed TIVBC is structured as an episode-of-care model with risk-based reimbursement for "referral/evaluation/waitlisting" (REW, referencing kidney transplantation), "primary hospitalization to 180 days posttransplant," and "long-term graft survival." Challenges around organ acquisition costs, adjustments to quality metrics, and potential criticisms of the proposed model are discussed. We propose next steps in risk-adjustment and cost-prediction to develop as an end-to-end, TIVBC model.

Development of a novel rapid response event review process for quality improvement.

INTRODUCTION: Rapid response team (RRT) and code activation events occur relatively commonly in inpatient settings. RRT systems have been the subject of a significant amount of analysis, although this has been largely focused on the impact of RRT system implementation and RRT events on patient outcomes. There is reason to believe that the structured assessment of RRT and code events may be an effective way to identify opportunities for system improvement, although no standardised approach to event analysis is widely accepted. We developed and refined a protocolised system of RRT and code event review, focused on sustainable, timely and high value event analysis meant to inform ongoing improvement activities. METHODS: A group of clinicians with expertise in process and quality improvement created a protocolised analytic plan for rapid response event review, piloted and then iteratively optimised a systematic process which was applied to all subsequent cases to be reviewed. RESULTS: Hospitalist reviewers were recruited and trained in a methodical approach. Each reviewer performed a chart review to summarise RRT events, and collect specific variables for each case (coding). Coding was then reviewed for concordance, at monthly interdisciplinary group meetings and 'Action Items' were identified and considered for implementation. In any 12-month period starting in 2021, approximately 12-15 distinct cases per month were reviewed and coded, offering ample opportunities to identify trends and patterns. CONCLUSION: We have developed an innovative process for ongoing review of RRT-Code events. The review process is easy to implement and has allowed for the timely identification of high value improvement opportunities.

Distinct transcriptional alterations distinguish Lewy body disease from Alzheimer's disease.

Lewy body dementia and Alzheimer's disease (AD) are leading causes of cognitive impairment, characterized by distinct but overlapping neuropathological hallmarks. Lewy body disease (LBD) is characterized by alpha-synuclein aggregates in the form of Lewy bodies as well as the deposition of extracellular amyloid plaques, with many cases also exhibiting neurofibrillary tangle (NFT) pathology. In contrast, Alzheimer's disease is characterized by amyloid plaques and neurofibrillary tangles. Both conditions often co-occur with additional neuropathological changes, such as vascular disease and TDP-43 pathology. To elucidate shared and distinct molecular signatures underlying these mixed neuropathologies, we extensively analyzed transcriptional changes in the anterior cingulate cortex, a brain region critically involved in cognitive processes. We performed bulk tissue RNAseq from the anterior cingulate cortex and determined differentially expressed genes (q-value < 0.05) in control (n = 81), Lewy body disease (n = 436), Alzheimer's disease (n = 53), and pathological amyloid cases consisting of amyloid pathology with minimal or no tau pathology (n = 39). We used gene set enrichment and weighted gene correlation network analysis (WGCNA) to understand the pathways associated with each neuropathologically defined group. Lewy body disease cases had strong up-regulation of inflammatory pathways and down-regulation of metabolic pathways. The Lewy body disease cases were further subdivided into either high Thal amyloid, Braak NFT, or low pathological burden cohorts. Compared to the control cases, the Lewy body disease cohorts consistently showed up-regulation for genes involved in protein folding and cytokine immune response, as well as down-regulation of fatty acid metabolism. Surprisingly, concomitant tau pathology within the Lewy body disease cases resulted in no additional changes. Some core inflammatory pathways were shared between Alzheimer's disease and Lewy body disease but with numerous disease-specific changes. Direct comparison of Lewy body disease cohorts versus Alzheimer's disease cases revealed strong enrichment of synaptic signaling, behavior, and neuronal system pathways. Females had a stronger response overall in both Lewy body and Alzheimer's disease, with several sex-specific changes. Overall, the results identify genes commonly and uniquely dysregulated in neuropathologically defined Lewy body disease and Alzheimer's disease cases, shedding light on shared and distinct molecular pathways. Additionally, the study underscores the importance of considering sex-specific changes in understanding the complex transcriptional landscape of these neurodegenerative diseases.

A Survey of Current Approaches to Inguinal Hernia Repair by Pediatric General Surgeons in the United States.

INTRODUCTION: Inguinal hernia repair (IHR) is a common pediatric operation performed via open or laparoscopic approaches. The objective of this survey study was to assess current approaches to IHR in a national sample of pediatric general surgeons. METHODS: A REDCap survey was distributed to all pediatric general surgeons at 21 US institutions in 2023. Descriptive statistics were used to analyze responses. RESULTS: The response rate was 70.0% (145/207) with median fellowship graduation year of 2011. Respondents reported they were primarily taught either an open (73.1%) or laparoscopic (6.9%) technique in fellowship, while 18.6% reported being taught both techniques equally. Overall, 60.7% of respondents reported currently performing both laparoscopic and open IHR, while 27.6% reported performing only open IHR and 11.7% reported performing only laparoscopic IHR. During unilateral open IHR, 75.8% of respondents check for and repair a contralateral inguinal hernia, most commonly by placing a laparoscope via the hernia sac (76.3%). Selective mesh use in adolescents was similar between laparoscopic and open repair approaches. For recurrent hernias, 37.2% of respondents indicated performing the approach that was not performed previously, while 38.6% and 22.8% indicated they routinely perform a laparoscopic or open approach, respectively, regardless of initial repair approach. CONCLUSION: Over two thirds of surgeons reported incorporating laparoscopic IHR into their practice despite nearly three-quarters of respondents indicating they were primarily taught an open approach in training. Training in laparoscopic IHR has been increasing over time, and respondents reported a wide variety of laparoscopic and open repair techniques. LEVEL OF EVIDENCE: IV.

Myotonic dystrophy type 1 testing, 2024 revision: A technical standard of the American College of Medical Genetics and Genomics (ACMG).

Myotonic dystrophy type 1 (DM1) is a form of muscular dystrophy causing progressive muscle loss and weakness. Although clinical features can manifest at any age, it is the most common form of muscular dystrophy with onset in adulthood. DM1 is an autosomal dominant condition, resulting from an unstable CTG expansion in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. The age of onset and the severity of the phenotype are roughly correlated with the size of the CTG expansion. Multiple methodologies can be used to diagnose affected individuals with DM1, including polymerase chain reaction, Southern blot, and triplet repeat-primed polymerase chain reaction. Recently, triplet repeat interruptions have been described, which may affect clinical outcomes of a fully-variable allele in DMPK. This document supersedes the Technical Standards and Guidelines for Myotonic Dystrophy originally published in 2009 and reaffirmed in 2015. It is designed for genetic testing professionals who are already familiar with the disease and the methods of analysis.