Search

Advancements in neoadjuvant regimens for esophageal adenocarcinoma have enabled some patients to achieve complete pathologic response at time of esophagectomy. There are currently limited data detailing this trend or the implications of complete pathologic response on survival. The National Cancer Database was used to identify 16,169 patients with esophageal adenocarcinoma that received trimodal therapy including esophagectomy between 2006 and 2020. Of these, 11.4% had complete pathologic response at esophagectomy. Patient factors, staging characteristics, and survival trends were evaluated. In patients diagnosed between 2016 and 2020, the rate of complete pathologic response was 17.5%. Female sex (OR 1.295, 95% CI 1.134-1.481, p = 0.0001), Black race (OR 1.729, 95% CI 1.362-2.196, p = 0.0002), Hispanic ethnicity (OR 1.418, 95% CI 1.073-1.875, p = 0.0141), and later era of diagnosis (2016-2020 OR 2.898, 95% CI 2.508-3.349, p < 0.0001) were independent predictors of complete pathologic response. Clinical stage II disease was associated with an increased probability of complete pathologic response (OR 1.492, 95% CI 1.19-1.871) while clinical stage III disease had a decreased probability of complete pathologic response (OR 0.762, 95% CI 0.621-0.936, p < 0.0001). Complete pathologic response conveyed a strong survival benefit, with a median survival of 86.4 months (95% CI 73.9-102.1) versus 30.7 months (95% CI 29.8-31.7, p < 0.0001) in those without complete pathologic response. Four-year median survival was also higher in those with complete pathologic response (63.3%, 95% CI 60.8-66.0% vs. 39.2%, 95% CI 38.4-40.1%, p < 0.0001). In summary, complete pathologic response is associated with a profound survival advantage in patients with esophageal adenocarcinoma. Such knowledge carries implications for patient counseling, prognostication, and surveillance and demonstrates a need for improved identification of complete clinical response prior to esophagectomy., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Micronutrient deficiencies are common and frequently co-occurring among people living with HIV (PLHIV) globally, with consequences for their health and clinical outcomes. Previous reviews of the influence of micronutrient supplementation on HIV outcomes were conducted in the pre-highly active antiretroviral therapy (pre-HAART) era or included both HAART-naive and HAART-experienced individuals; thus, the evidence in the context of HAART is inconclusive., Objective: A systematic review and meta-analysis was conducted to evaluate the effect of micronutrient supplementation on important clinical outcomes among PLHIV on HAART., Data Sources: Original research articles published up to August 2022 in the following medical literature databases were identified and examined: PubMed/Medline, Embase, Web of Science, and Google Scholar., Data Extraction: Randomized controlled trials (RCTs) and pre-post intervention studies that evaluated the relationship of micronutrient supplementation and HIV-related outcomes were included. A total of 32 studies investigating the effect of micronutrient supplementation on HIV outcomes in PLHIV on HAART were included. The main outcomes of interest were disease progression, CD4 lymphocyte count, viral load, weight, body mass index (BMI), hemoglobin, and anemia. The Cochrane Risk of Bias (RoB) 2 and ROBINS-I tools were used to assess the risk of bias in included studies, and GRADE was used to assess the certainty of the evidence., Data Analysis: Vitamin D supplementation increased serum 25-hydroxyvitamin D concentration by 23.2 nmol/L (95% CI: 11.8 to 34.6; 6 RCTs, 567 participants; low-certainty evidence), but had little to no effect on CD4 lymphocyte counts (mean difference [MD]: 60 cells/µL; 95% CI: -35 to 155; 4 RCTs, 127 participants; low-certainty evidence). The effect of vitamin D on CD4 lymphocyte counts was greater among those with baseline CD4 count <350 cells/µL compared with counterparts with higher CD4 lymphocyte counts. Evidence from single RCTs suggests a beneficial effect of vitamin D on the incidence of sputum-smear-positive tuberculosis (hazard ratio = 0.54; 95% CI: 0.31, 0.92; 4000 participants; low-certainty evidence), and vitamin E (MD = 0.2 g/dL; 95% CI: 0.1, 0.3; 18 participants; moderate-certainty evidence) and selenium (MD = 0.30 g/dL; 95% CI: 0.29, 0.31; 97 participants; high-certainty evidence) on hemoglobin, and selenium on BMI (MD: -0.5; 95% CI: -0.51, -0.49; high-certainty evidence). Zinc supplementation had little to no effect on CD4 lymphocyte count overall, but for every 10-µg/dL higher serum zinc concentration, the predicted change in CD4 lymphocyte count from meta-regression was lower by 28 cells/µL (95% CI: -54, -3; 5 RCTs). Moderate- or high-certainty evidence indicates that there is probably no effect of zinc supplementation on log10 viral load, vitamin D on BMI and lumbar spine bone mineral density, and multiple micronutrient (MMN) supplementation on hemoglobin. The evidence is very uncertain about the effect of zinc supplementation on hemoglobin concentration and BMI, vitamin D supplementation on lumbar spine bone mineral density, vitamin E on CD4 lymphocyte count, and MMN supplementation on CD4 lymphocyte count., Conclusion: Zinc and vitamin D supplementation may promote immune recovery in a substantial proportion of PLHIV on HAART, and selenium and vitamin E supplementation may prevent anemia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Associations between immune-related adverse events (irAEs) from checkpoint inhibitor therapy and outcomes have been previously evaluated, with most prior research finding a positive association between toxicity and survival. This prior research has generally reported on more common tumor types. We use a unique data resource of a federally-funded basket trial ((NCT02834013) for patients with rare cancers (N = 684) to evaluate associations between irAEs and overall survival and progression-free survival., Methods: Patients were treated with nivolumab and ipilimumab; the trial was opened at > 1000 sites. Landmark Cox regression models were used to assess first cycle irAE associations with progression-free and overall survival., Results: We found that grade 1-2 treatment-related irAEs in the first cycle of therapy were associated with longer overall survival (OS) (multivariable hazard ratio, 95% confidence interval, p-value: 0.61, 0.49-0.75, p < .001) compared to no treatment-related irAE, while grade 3-4 irAEs were associated with shorter OS (HR = 1.41, 95% CI = 1.04-1.90, p = .025). Similar, but weaker, associations were observed with progression-free survival (PFS) and grade 1-2 treatment-related irAEs: HR = 0.83, 95% CI = 0.67-1.01, p = .067 and grade 3-4: HR = 1.35, 95% CI = 1.02-1.78, p = .037 compared to no treatment-related irAEs. Grade 1-2 dermatologic toxicity was associated with improved OS compared to other grade 1-2 toxicities (HR = 0.67, 95% CI = 0.52-0.85, p = .002). There was no significant OS difference between patients with Grade 1-2 fatigue, gastrointestinal, metabolic, hepatic, endocrine, and thyroid toxicities vs other Grade 1-2 toxicities., Conclusions: In this large cohort of patients with rare tumors receiving checkpoint inhibitor therapy, grade of irAE in the first cycle was predictive for survival., (Published by Oxford University Press 2024.)

The Veterans Health Administration (VHA) provides maternity care by paying for Veterans to receive pregnancy-related care in community settings and by utilizing maternity care coordinators (MCCs) at each medical facility. The purpose of this qualitative descriptive study was to understand the MCC's experiences performing their role across VA facilities. Thirty MCCs were recruited and interviewed virtually using Microsoft Teams. Interviews were recorded and transcribed verbatim. Using thematic analysis, transcripts were coded, and themes were derived. MCC's roles include being a liaison, care coordinator, and supporter. MCCs improve Veterans' care during pregnancy and postpartum by education, monitoring health status, and connecting Veterans to providers within VA and the community. Across VA facilities, there was variation in how MCCs engaged with Veterans and in the services provided. A challenge shared was the lack of dedicated time to the role. In the VA, MCCs are valuable in ensuring high-quality care coordination of pregnant/postpartum Veterans despite the fragmentation of care between VA and community providers. To improve inconsistencies in how the MCC program is implemented, systematic strategies such as ensuring dedicated time are needed., (Published by Oxford University Press on behalf of the Society of Behavioral Medicine 2024.)

Soft casts have been introduced as an efficacious strategy to manage hand burns that simplifies wound care for families. We hypothesized that the outpatient use of soft casts in pediatric hand burns would be viewed as acceptable by patient caregivers and providers, logistically feasible, and result in satisfactory clinical outcomes. A review was performed of pediatric clinic patients managed with soft casts since implementation (9/2022-9/2023). Patient caregivers and providers were surveyed. The primary outcome was the acceptability of soft casts as a management strategy (questions targeted care burden, overall satisfaction, comfort, pragmatism, and healing concerns). The secondary outcome was feasibility (effect on clinic workflow, and efficiency). Survey responses were collected from 70% of caregivers and 95% of providers. Responses overwhelmingly favored soft cast acceptability. Among providers, 84% agreed that "the soft cast method simplified the hand burn care experience in our clinic" and 100% indicated "the soft cast was easy for parents to manage at home" (Likert range 7-10, mode 10). Thirty-three English-speaking patients with partial and full-thickness hand burns were managed with soft casts. A mean of 1.8 reapplications (mode 1, range 1-5) was required with a median healing time of 13 days. No infections were attributed to the use of soft casting, and only 1 patient ultimately required grafting. Overall, the introduction of soft casts as a management strategy for pediatric hand burns was acceptable and feasible. The clinical outcomes assessed suggest soft casts are associated with good wound healing with minimal wound care responsibilities for patients and families., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was success in 66 participants transitioned to enteral therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Genome-wide association studies typically evaluate the autosomes and sometimes the X Chromosome, but seldom consider the Y or mitochondrial (MT) Chromosomes. We genotyped the Y and MT Chromosomes in heterogeneous stock (HS) rats (Rattus norvegicus), an outbred population created from 8 inbred strains. We identified 8 distinct Y and 4 distinct MT Chromosomes among the 8 founders. However, only 2 types of each nonrecombinant chromosome were observed in our modern HS rat population (generations 81-97). Despite the relatively large sample size, there were virtually no significant associations for behavioral, physiological, metabolome, or microbiome traits after correcting for multiple comparisons. However, both Y and MT Chromosomes were strongly associated with the expression of a few genes located on those chromosomes, which provided a positive control. Our results suggest that within modern HS rats there are no Y and MT Chromosomes differences that strongly influence behavioral or physiological traits. These results do not address other ancestral Y and MT Chromosomes that do not appear in modern HS rats, nor do they address effects that may exist in other rat populations, or in other species., Competing Interests: Conflicts of interest RK is a scientific advisory board member, and consultant for BiomeSense, Inc., has equity and receives income. He is a scientific advisory board member and has equity in GenCirq. He is a consultant for DayTwo, and receives income. He has equity in and acts as a consultant for Cybele. He is a co-founder of Biota, Inc., and has equity. He is a cofounder of Micronoma, and has equity and is a scientific advisory board member. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Introduction: Warfighters are issued hard body armor designed to defeat ballistic projectiles. The resulting backface deformation can injure different thoracoabdominal organs. Developed over decades ago, the behind armor blunt impact criterion of maximum 44 mm depth in clay continues to be used independent of armor type or impact location on the thoracoabdominal region covered by the armor. Because thoracoabdominal components have different energy absorption capabilities, their mode of failures and mechanical properties are different. These considerations underscore the lack of effectiveness of using the single standard to cover all thoracoabdominal components to represent the same level of injury risk. The objective of this pilot study is to conduct cardiac impact tests with a live animal model and analyze biomechanical injury candidate metrics for behind armor blunt trauma applications., Materials and Methods: Live swine tests were conducted after obtaining approvals from the U.S. DoD. Trachea tubes. An intravenous line were introduced into the swine before administering anesthesia. Pressure transducers were inserted into lungs and aorta. An indenter simulating backface deformation profiles produced by body armor from military-relevant ballistics to human cadavers delivered impact to the heart region. The approved test protocol included 6-hour monitoring and necropsies. Indenter accelerometer signals were processed to compute the velocity and deflection, and their peak magnitudes were obtained. The deflection-time signal was normalized with respect to chest depth along the impact axis. The peak magnitude of the viscous criterion, kinetic energy, force, momentum and stiffness were obtained., Results: Out of the 8 specimens, 2 were sham controls. The mean total body mass and soft tissue thickness at the impact site were 81.1 ± 4.1 kg and 3.8 ± 1.1 cm. The peak velocities ranged from 30 to 59 m/s, normalized deflections ranged from 15 to 21%, and energies ranged from 105 to 407 J. The range in momentum and stiffness were 7.0 to 13.9 kg-m/s and 22.3 to 79.9 N/m. The maximum forces and impulse data ranged from 2.9 to 11.7 kN and 1.9 to 5.8 N-s. The peak viscous criterion ranged from 2.0 to 5.3 m/s. One animal did not sustain any injuries, 2 had cardiac injuries, and others had lung and skeletal injuries., Conclusions: The present study applied blunt impact loads to the live swine cardiac region and determined potential candidate injury metrics for characterization. The sample size of 6 swine produced injuries ranging from none to pure skeletal to pure organ trauma. The viscous criterion metric associated with the response of the animal demonstrated a differing pattern than other variables with increasing velocity. These findings demonstrate that our live animal experimental design can be effectively used with testing additional samples to develop behind armor blunt injury criteria for cardiac trauma in the form of risk curves. Injury criteria obtained for cardiac trauma can be used to enhance the effectiveness of the body armor, reduce morbidity and mortality, and improve warfighter readiness in combat operations., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

In multiple myeloma (MM), while frequent mutations in driver genes are crucial for disease progression, they traditionally offer limited insights into patient prognosis. This study aims to enhance prognostic understanding in MM by analyzing pathway dysregulations in key cancer driver genes, thereby identifying actionable gene signatures. We conducted a detailed quantification of mutations and pathway dysregulations in 10 frequently mutated cancer driver genes in MM to characterize their comprehensive mutational impacts on the whole transcriptome. This was followed by a systematic survival analysis to identify significant gene signatures with enhanced prognostic value. Our systematic analysis highlighted 2 significant signatures, TP53 and LRP1B, which notably outperformed mere mutation status in prognostic predictions. These gene signatures remained prognostically valuable even when accounting for clinical factors, including cytogenetic abnormalities, the International Staging System (ISS), and its revised version (R-ISS). The LRP1B signature effectively distinguished high-risk patients within low/intermediate-risk categories and correlated with significant changes in the tumor immune microenvironment. Additionally, the LRP1B signature showed a strong association with proteasome inhibitor pathways, notably predicting patient responses to bortezomib and the progression from monoclonal gammopathy of unknown significance to MM. Through a rigorous analysis, this study underscores the potential of specific gene signatures in revolutionizing the prognostic landscape of MM, providing novel clinical insights that could influence future translational oncology research., (© The Author(s) 2024. Published by Oxford University Press.)

Ceroid lipofuscinosis neuronal (CLN) encompasses rare inherited neurodegenerative disorders that present in childhood with clinical features including epilepsy, psychomotor delay, progressive vision loss, and premature death. Published experience utilizing umbilical cord blood transplant (UCBT) for these disorders is limited. This retrospective analysis includes patients with CLN (2, 3, and 5) who underwent UCBT from 2012 to 2020. All subjects (n = 8) received standard-of-care myeloablative conditioning. Four also enrolled in clinical trial NCT02254863 and received intrathecal DUOC-01 cells posttransplant. Median age at UCBT was 5.9 years. All subjects achieved neutrophil engraftment with >95% donor chimerism at a median of 28.5 days. Sinusoidal obstructive syndrome was not observed. Severe acute graft-versus-host disease occurred in 12.5%. Other complications included autoimmune hemolytic anemia (25%) and viral reactivation/infection (62.5%). No transplant-related mortality was observed. Two CLN2 patients died, 1 from progressive disease and 1 from unknown cause at days +362 and +937, respectively. With median follow-up of 8 years, overall survival at 100 days and 24 months was 100% and 88%, respectively. Three of 4 CLN3 subjects stabilized Hamburg motor and language scores. While UCBT appears safe and feasible in these patients, given the variable expression and natural history, extended follow-up and further studies are needed to elucidate the potential impact of UCBT on clinical outcomes., (© The Author(s) 2024. Published by Oxford University Press.)

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents-yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 2 of 3) summarizes the current state of laboratory and point-of-care diagnostic testing and highlights the expanding role of nucleic acid amplification in the expedited diagnosis and management of patients with acute pharyngitis. It discusses preanalytical, analytical, and postanalytical variables that impact the performance of culture, rapid antigen, and nucleic acid amplification testing. Finally, it sets the stage for part 3, which discusses the emerging role of biomarkers in the management of individuals with acute pharyngitis., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents-yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This article (part 1 of 3) summarizes the impact of acute pharyngitis on the health care system and reviews the etiologic agents of acute pharyngitis, including both emerging and reemerging pathogens that health care providers should consider when evaluating their patients. Finally, it sets the stage for parts 2 and 3, which discuss the current and evolving state of diagnostic testing for acute pharyngitis., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: The NIH All of Us Research Program aims to advance personalized medicine by not only linking patient records, surveys, and genomic data but also engaging with participants, particularly from groups traditionally underrepresented in biomedical research (UBR). This study details how the dialogue between scientists and community members, including many from communities of color, shaped local research priorities., Materials and Methods: We recruited area quantitative, basic, and clinical scientists as well as community members from our Community and Participant Advisory Boards with a predetermined interest in All of Us research as members of a Special Interest Group (SIG). An expert community engagement scientist facilitated 6 SIG meetings over the year, explicitly fostering openness and flexibility during conversations. We qualitatively analyzed discussions using a social movement framework tailored for community-based participatory research (CBPR) mobilization., Results: The SIG evolved through CBPR stages of emergence, coalescence, momentum, and maintenance/integration. Researchers prioritized community needs above personal academic interests while community members kept discussions focused on tangible return of value to communities. One key outcome includes SIG-driven shifts in programmatic and research priorities of the All of Us Research Program in Southeastern Wisconsin. One major challenge was building equitable conversations that balanced scientific rigor and community understanding., Discussion: Our approach allowed for a rich dialogue to emerge. Points of connection and disconnection between community members and scientists offered important guidance for emerging areas of genomic inquiry., Conclusion: Our study presents a robust foundation for future efforts to engage diverse communities in CBPR, particularly on healthcare concerns affecting UBR communities., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2024.)

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents-yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 3 of 3) summarizes the current state of biomarker diagnostic testing and highlights the expanding role they will likely play in the expedited diagnosis and management of patients with acute pharyngitis. Biomarkers, in conjunction with rapid antigen and/or nucleic acid amplification testing, will likely become the standard of care to accurately diagnose the etiologic agent(s) of pharyngitis. This novel testing paradigm has the potential to guide appropriate patient management and antibiotic stewardship by accurately determining if the cause of pharyngitis is due to a viral or bacterial etiology., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Postsurgical pyoderma gangrenosum (PSPG) is a rare, ulcerative skin condition that presents a diagnostic challenge due to its similar presentation to infectious etiologies in the postsurgical period-often leading to gratuitous and unnecessary surgery and antibiotic use. We report a 37-year-old female with breast cancer who received neoadjuvant chemotherapy and immunotherapy and underwent bilateral skin-sparing mastectomies who developed delayed bilateral mastectomy skin flap necrosis secondary to PSPG. This case had rare factors associated with the development of PSPG such as preoperative systemic therapy and a familial component. This case underscores the importance of early recognition of this rare disease and appropriate management of PSPG to prevent unnecessary interventions and ensure an optimal outcome., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Temporal lobe (TL) epilepsy surgery is an effective treatment option for patients with drug-resistant epilepsy. However, neurosurgery poses a risk for cognitive deficits - up to one third of patients have a decline in naming ability following TL surgery. In this study, we aimed to better understand the neural correlates associated with reduced naming performance after TL surgery, with the goal of informing surgical planning strategies to mitigate the risk of dysnomia. We retrospectively identified 85 patients who underwent temporal lobe (TL) resective surgery (49 left TL, 36 right TL) for whom naming ability was assessed before and >3 months post-surgery using the Boston Naming Test (BNT). We used multivariate lesion-symptom mapping to identify resection sites associated with naming decline, and we used lesion-network mapping to evaluate the broader functional and structural connectivity profiles of resection sites associated with naming decline. We validated our findings in an independent cohort of 59 individuals with left temporal lobectomy, along with repeating all analyses after combining the cohorts. Lesion laterality and location were important predictors of post-surgical naming performance. Naming performance significantly improved after right temporal lobectomy (P = 0.015) while a decrement in performance was observed following left temporal lobectomy (P = 0.002). Declines in naming performance were associated with surgical resection of the left anterior middle temporal gyrus (Brodmann area 21, r =0.41, P = <.001), along with a previously implicated basal temporal language area. Resection sites linked to naming decline showed a functional connectivity profile featuring a left-lateralized network closely resembling the extended semantic \ default mode network, and a structural connectivity profile featuring major temporo-frontal association white matter tracts coursing through the temporal stem. This extends prior work by implicating the left anterior middle temporal gyrus in naming decline and provides additional support for the role of the previously identified basal temporal language area in naming decline. Importantly, the structural and functional connectivity profiles of these regions suggest they are key nodes of a broader extended semantic network. Together these regional and network findings may help in surgical planning and discussions of prognosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Gene sequencing has brought a titanic of complex data into clinical precision oncology. Deciphering this complexity for practice requires new constructs. In 2014, the Molecular Tumor Board (MTB) was introduced into the literature by a publication in The Oncologist. Ten years later, MTBs have become globally established vehicles that integrate rapidly emerging "omic" information, helping to transform cancer management., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab)., Methods: We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization., Results: Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 μg/mL [P = .49]; adalimumab: 11.1 vs 10.5 μg/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 μg/mL [P < .01]; adalimumab: 9.1 vs 12.3 μg/mL [P < .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14)., Conclusions: LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Context: Little is known about how patients' emotions impact the choice between hemi- and total thyroidectomy (TT) for low-risk thyroid cancer (LR-TC) and how these emotions change after treatment., Objective: To investigate thyroid cancer-specific fear and worry both before and after treatment of LR-TC with hemi- or TT., Methods: This prospective cohort study enrolled adults with confirmed or likely LR-TC at 15 institutions. Participants completed measures of thyroid cancer-related fear and worry at the time of their treatment decision and 9-months later. Participants were categorized as having low, medium, or high levels of fear and worry in accordance with the literature. Those choosing hemi-thyroidectomy were compared to those choosing TT., Results: Of 177eligible patients, 125 (70.6%) enrolled and 114 completed both surveys (91.2% retention). Overall, 41 (36.0%) participants chose hemi-thyroidectomy and 73 (64.0%) chose TT. Across all participants, thyroid cancer-related fear and worry both decreased significantly after surgery (fear 25.8±6.4 to 23.1±7.4; worry 8.2±2.4 to 5.4±2.1, p<0.001). The proportion of participants with high fear decreased from 64.9% to 50.9%, while the proportion with high worry decreased from 75.4% to 41.2% (p<0.001 for both). At both time points, no differences existed between those choosing hemi- and TT in levels of worry or fear., Conclusion: Patients with LR-TC report lower levels of fear and worry 9-months after surgery regardless of the extent of surgery, suggesting that both surgeries provide an emotional benefit to some patients. Thyroid cancer-related fear and worry do not appear to influence patients' decisions to undergo hemi- or TT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: While nearly 50% of adult women report at least one episode of urinary incontinence (UI), most never receive treatment., Objective: To better integrate primary and specialty UI care, we conducted (i) an environmental scan to assess the availability of key pathway resources in primary care, (ii) interviews with primary care providers to understand barriers to care, and (iii) a pilot UI care pathway intervention., Methods: Environmental scan: Clinic managers from all primary care clinics within a Midwestern healthcare system were invited to participate in an interview covering the availability of clinic resources. Provider interviews: Primary care providers were invited to participate in an interview covering current practices and perceived barriers to UI care. Pilot UI care pathway: Patients who screened positive for UI were provided resources for first-line behavioral management. Pilot patients completed questionnaires at baseline, 8 weeks, and 6 months., Results: While many clinics had point-of-care urinalysis (17/21, 81%), most did not have a working bladder ultrasound (14/21, 67%) or on-site pelvic floor physical therapy (18/21, 86%). Providers (n = 5) described barriers to completing almost every step of diagnosis and treatment for UI. The most persistent barrier was lack of time. Patients (n = 15) reported several self-treatment strategies including avoiding bladder irritants (7/15, 47%) and performing Kegel exercises (4/15, 27%). Five patients (33%) requested follow-up care. At 6 months, patients reported small improvements in UI symptoms., Conclusion: Promising results from a novel UI care pathway pilot indicate that streamlining UI care may assist primary care providers in the first-line treatment of UI., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO)., Materials and Methods: This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs., Results: Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9)., Conclusions: IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era., (© The Author(s) 2023. Published by Oxford University Press.)

Objectives: To assess self-reported symptoms of neuropathy, disability, pain, health-related quality of life (HR-QOL) and autonomic dysfunction in patients with vasculitis., Methods: Patients with vasculitis (with or without neuropathy) were invited by Vasculitis UK to complete an anonymous online survey., Results: Three hundred and twelve patients (71% female) responded. Median age was 61-70 years. Median duration of vasculitis was 4 years (<2 months to >15 years). Vasculitic types included granulomatosis with polyangiitis (34%), unspecified ANCA-associated vasculitis (13%), microscopic polyangiitis (11%), eosinophilic granulomatosis with polyangiitis (11%), giant cell arteritis (10%), non-systemic vasculitic neuropathy (2%) and other (19%). Many patients reported foot/hand symptoms suggestive of neuropathy, including numbness (64%), pain (54%) or weakness (40%). Two hundred and forty-two patients (78%) met our definition of probable vasculitic neuropathy: diagnosis of neuropathy by vasculitis team OR numbness OR weakness in feet/hands. Only 52% had been formally diagnosed with neuropathy. Compared with 70 patients without neuropathy, neuropathy patients had greater disability measured by the inflammatory Rasch-built Overall Disability Scale (centile mean 63.1 [s.d. 17.3] vs 75.2 [16.7]; P < 0.0001), Inflammatory Neuropathy Cause and Treatment scale (median 2 [interquartile range 1-4] vs 0.5 [0-2]; P < 0.0001) and modified Rankin scale (median 2 [interquartile range 1-3] vs 2 [1-2)]; P = 0.0002); greater pain on an 11-point rating scale (mean 4.6 [s.d. 2.6] vs 3.5 [2.8]; P = 0.0009); and poorer HR-QOL on the EQ5D-3L (summary index mean 0.58 [s.d. 0.29] vs 0.69 [0.28]; P < 0.0001). Two-thirds reported autonomic symptoms (not associated with neuropathy)., Conclusion: Neuropathy is common and associated with significant disability, pain and impaired HR-QOL in patients with systemic vasculitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The causal relationship between certain immune cells and erectile dysfunction (ED) is still uncertain., Aim: The study sought to investigate the causal effect of 731 types of immune cells on ED through Mendelian randomization (MR) using genome-wide association studies (GWAS)., Methods: Genetic instruments for 731 immune cells were identified through GWAS, and ED data were obtained from the FinnGen database. Univariable and multivariable bidirectional MR studies were conducted to explore potential causal relationships between these immune cells and ED. The inverse-variance weighted method was primarily used, with Cochran's Q test and MR-Egger intercept test assessing pleiotropy and heterogeneity. Bayesian weighted Mendelian randomization (BWMR) was also employed., Outcomes: Six immune cells were identified as related to ED. CD45 on Natural Killer (NK) cells, CD33dim HLA DR+ CD11b + Absolute Count, CD19 on IgD- CD38dim B cells, and CD3 on CD39+ resting CD4 regulatory T cells were identified as risk factors, whereas CD20 on IgD+ CD38dim B cells and Activated & resting CD4 regulatory T cell %CD4+ T cells were protective factors. Further multivariable MR analysis confirmed that 5 of these immune cells independently impacted ED, except for CD45 on NK cells. Reverse MR analysis indicated that ED occurrence decreases certain immune cell counts, but BWMR found no causal relationship for CD20 on IgD+ CD38dim B cells., Results: Our MR analysis confirmed a potential bidirectional causal relationship between immune cells and ED, providing new insights into potential mechanisms and therapeutic strategies., Clinical Translation: This study provides evidence for the impact of certain immune cells on the development of ED and suggests potential therapeutic targets., Strengths and Limitations: We performed both univariable and multivariable MR to strengthen the causal relationship between exposures and outcomes. However, the population in this study was limited to European ancestry., Conclusion: Our MR analysis confirmed a potential bidirectional causal relationship between immune cells and ED. This provides new insights into potential mechanisms of pathogenesis and subsequent therapeutic strategies., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine.)

Objectives: Selection of autoimmune/paraneoplastic antibody panels remains challenging because health-care professionals often lack familiarity with panel contents, recommended specimen types, and antibody combinations for a given patient. Inappropriate use adds cost, prompts unnecessary additional workup, and delays the identification of the true cause of patient symptoms. In this study, we assessed whether order-entry clinical decision support can improve autoimmune/paraneoplastic antibody panel utilization., Methods: An order-entry clinical decision support tool was embedded in the electronic health record system. Using a nested panel structure, the decision support tool prompted clinicians to identify their patient's clinical presentation and guided selection of the appropriate tests. In addition, the tool featured a duplicate checking function to alert clinicians when placing multiple orders with substantially similar antibody content within a 3-month period. Panel ordering practices were assessed during the 12 months before implementation and compared with the 6 months immediately following implementation., Results: Clinical decision support significantly reduced the monthly test volume of all orderables from 75.8 per month before implementation to 54.5 per month after implementation (incident rate ratio [IRR], 0.72; 95% CI, 0.63-0.81; P < .001). Placement of multiple orders for panels with substantially overlapping antibody content also decreased significantly, from 7.0 per month to 1.2 per month (IRR, 0.17; 95% CI, 0.07-0.33; P < .001). The number of neural-specific antibodies detected remained unchanged, but the reduction in total test volume increased the neural-specific antibody positivity rate from 4.2% to 6.8% (IRR, 1.61; 95% CI, 0.94-2.70; P = .075)., Conclusions: Order-entry clinical decision support offers an efficient and effective approach to improve the utilization of autoimmune/paraneoplastic antibody panels., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To evaluate the utilization of hematopathology resources within our enterprise on axillary lymph node core biopsy (AxLNCB) specimens, particularly those obtained in the context of breast cancer screening., Methods: The utilization of hematopathology resources was determined for all AxLNCB specimens over a 30-month period from across our enterprise, and chart review was performed for select patient demographics and radiographic features. The AxLNCB cases with benign histology were reviewed for subtyping of histologic patterns., Results: Of the total 594 AxLNCB specimens, 61.6% were benign and 38.6% malignant. Of malignant cases, only 9.3% contained any hematologic malignancy, yet 94% of all cases received tissue triage for lymphoma, and 81% were reviewed at least in part by a hematopathologist. Six clinical parameters were found to independently predict risk of hematologic malignancy: male sex (P = .041), bilateral lymphadenopathy (P = .004), diffuse cortical thickening (P = .005), lack of breast cancer (P = .001), older age (P < .001), and history of hematologic malignancy (P < .001)., Conclusions: Our enterprise overused hematopathology resources in the evaluation of AxLNCB performed in the study period. Our process could improve from the application of a simple tool generated from this cohort to predict percent risk of the specimen containing hematologic malignancy using patient characteristics easily found via routine chart review., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Anal cancer risk is elevated among people with HIV. Recent anal cancer incidence patterns among people with HIV in the United States and Canada remain unclear. It is unknown how the incidence patterns may evolve., Methods: Using data from the North American AIDS Cohort Collaboration on Research and Design, we investigated absolute anal cancer incidence and incidence trends nationally in the United States and Canada and in different US regions. We further estimated relative risk compared with people without HIV, relative risk among various subgroups, and projected future anal cancer burden among American people with HIV., Results: Between 2001 and 2016 in the United States, age-standardized anal cancer incidence declined 2.2% per year (95% confidence interval = ‒4.4% to ‒0.1%), particularly in the Western region (‒3.8% per year, 95% confidence interval = ‒6.5% to ‒0.9%). In Canada, incidence remained stable. Considerable geographic variation in risk was observed by US regions (eg, more than 4-fold risk in the Midwest and Southeast compared with the Northeast among men who have sex with men who have HIV). Anal cancer risk increased with a decrease in nadir CD4 cell count and was elevated among those individuals with opportunistic illnesses. Anal cancer burden among American people with HIV is expected to decrease through 2035, but more than 70% of cases will continue to occur in men who have sex with men who have HIV and in people with AIDS., Conclusion: Geographic variation in anal cancer risk and trends may reflect underlying differences in screening practices and HIV epidemic. Men who have sex with men who have HIV and people with prior AIDS diagnoses will continue to bear the highest anal cancer burden, highlighting the importance of precision prevention., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Squamous cell carcinoma of the anus (SCCA) incidence has been rising in the United States, particularly among older adults (≥65 years). We estimated the impact of this rise on future burden (through 2035) using age-period-cohort modeling. The SCCA burden (cases/year) is expected to rise, reaching approximately 2700 among men and approximately 7000 among women in 2031-2035 (burden during 2016-2020 among men and women was approximately 2150 and approximately 4600), with most cases 65 years of age or older (61% in men and 70% in women in 2031-2035; from 40% and 46% in 2016-2020). SCCA incidence (per 100 000) is projected to rise among older men aged 65-74, 75-84, and 85 years or older (5.0, 4.9, and 4.3 in 2031-2035 vs 3.7, 3.8, and 3.4 in 2016-2020, respectively) and women (11.2, 12.6, and 8.0 in 2031-2035 vs 8.2, 6.8, and 5.2 in 2016-2020, respectively). The projected rise in SCCA burden among older adults is troubling and highlights the importance of improving early detection and clinical care., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: We evaluated whether plasma Alzheimer disease (AD)-related biomarkers were associated with cancer-related cognitive decline among older breast cancer survivors., Methods: We included survivors aged 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched noncancer control paricipant (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (presystemic therapy) and annually for up to 60 months. Cognition was measured using tests of attention, processing speed, and executive function and learning and memory; perceived cognition was measured by the Functional Assessment of Cancer Therapy-Cognitive Function v3 Perceived Cognitive Impairments. Baseline plasma neurofilament light, glial fibrillary acidic protein, β-amyloid 42 and 40 and phosphorylated tau 181 were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD biomarkers, time, group (survivor vs control participant), and their 2- and 3-way interactions, controlling for age, race, Wide Range 4 Achievement Test Word Reading score, comorbidity, and body mass index; 2-sided P values of .05 were considered statistically significant., Results: There were no group differences in baseline AD-related biomarkers except survivors had higher baseline neurofilament light levels than control participants (P = .013). Survivors had lower adjusted longitudinal attention, processing speed, and executive function than control participants starting from baseline and continuing over time (P ≤ .002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except control participants had lower attention, processing speed, and executive function scores with higher glial fibrillary acidic protein levels (P = .008)., Conclusion: The results do not support a relationship between baseline AD-related biomarkers and cancer-related cognitive decline. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers, and examine other mechanisms and factors affecting cognition presystemic therapy., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Maternal morbidity is higher among the Veteran population in part because of high rates of chronic medical and mental health conditions. To improve care for pregnant Veterans, the Department of Veteran Affairs created the position of the Maternity Care Coordinator (MCC) to provide care coordination during a Veteran's pregnancy. Maternity Care Coordinators must work with primary care providers (PCPs); yet, little is known about their collaboration and interaction. The objective of this work is to better understand how MCCs interact with PCPs., Method: Between March and May of 2021, we conducted qualitative interviews with 30 MCCs using a semi-structured interview guide to learn about their role and interactions with PCPs., Results: We identified 3 main themes in interactions between MCCs and PCPs, which correlated to times during the Veteran's pregnancy: initial interactions, care coordination during the pregnancy, and end of pregnancy transitions of care. Most MCCs indicated a positive and collaborative relationship with PCPs. There was significant variability in how closely MCCs worked with PCPs. MCCs reported that PCPs were not always comfortable caring for pregnant Veterans., Discussion: Although MCCs generally indicated a positive and collaborative interaction with PCPs, our data suggest that there are opportunities to improve communication between PCPs and MCCs and to educate PCPs on knowledge of maternity benefits, the role of the MCC, and how to care for pregnant and postpartum Veterans. The Veteran Affairs MCC can also serve as a model for other health systems aiming to improve care coordinator among pregnant patients., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: While intermittent fasting leads to weight loss and improved glucose metabolism, food insecurity, the insufficient access to food for a healthy life, is associated with obesity and adverse cardiometabolic health, especially in women. We aimed to characterize the effects of intermittently restricted feeding on energy balance and glucose tolerance in female mice., Methods: Female C57BL/6J mice were fed a high-fat, high-sucrose diet and intermittently food restricted to 60% of control littermates' ad libitum intake, starting at weaning and until week 19. Restricted mice were subsequently allowed ad libitum access to the same diet. Body composition and energy balance were measured at weeks 18.5, 19, 30, and 40. At week 42, mice underwent an intraperitoneal glucose tolerance test and plasma appetitive hormones measurements after nutrient gavage., Results: During the food restriction phase, restricted mice accrued lower weight and fat mass than controls despite periodic ad libitum food access. Reintroduction of continuous ad libitum food caused increased food intake during the light phase and increased body mass in restricted mice. Minor differences in body composition-adjusted energy expenditure between groups were observed at week 40. At week 42, glucose tolerance was impaired in restricted mice compared to controls, and trends toward lower levels of postprandial anorexigenic hormones glucagon-like peptide-1 and pancreatic polypeptide were observed., Conclusion: Our findings suggest that repeated intermittent food restriction leads to changes in eating behavior that predispose to glucose intolerance when food is freely available. Future studies are needed to elucidate the specific mechanisms underlying these changes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Introduction: This study examined the association between current co-use of cannabis and cigarettes in the past 30 days, and subsequent cigarette discontinuation (past 30-day point prevalence abstinence) among U.S. adults with established cigarette use in the Population Assessment of Tobacco and Health (PATH) Study. Additionally, we investigated the impact of co-use on the subsequent discontinuation of all combustible tobacco products., Methods: A total of 26,381 observations contributed by 8,218 adults with established cigarette use (i.e., smoked ≥ 100 cigarettes in their lifetime, and currently smoking cigarettes every day or some days) from Waves 1-5 of the PATH Study were included in the analysis. Weighted Generalized Estimating Equations (GEE) models were used to evaluate the association between current co-use at baseline (Waves 1-4) with the outcomes assessed at the subsequent wave (cigarette and combustible tobacco discontinuation at Waves 2-5). Final models included: demographic characteristics (age, sex, race and ethnicity, educational attainment), behavior characteristics (intention to quit, internalizing symptoms, externalizing symptoms, substance use problems), and wave-pair., Results: Over one-third (35.91%) of cigarette users self-reported co-use during the study period. Cannabis use among adults with established cigarette use increased over time. Co-use was associated with a decreased odds of cigarette smoking discontinuation at follow-up, after adjusting for covariates (aOR: 0.81; 95% CI: 0.72, 0.93; p=0.0018). Similar effect sizes were observed for discontinuation of all combustible tobacco products (aOR: 0.75; 95% CI: 0.65, 0.86; p<.0001)., Conclusions: Cannabis use among adults who smoke cigarettes was inversely related to subsequent cigarette discontinuation, suggesting that co-use may reduce likelihood of successful tobacco cessation., Implications: Findings demonstrate that cannabis use may lead to lower odds of discontinuation among adults with established cigarette use; therefore, individuals that co-use cigarettes and cannabis may need additional tobacco cessation support. Notably, this study observed an increase in co-use of cigarettes and cannabis, emphasizing the need for researchers and public health programs to shift their focus towards understanding and addressing concurrent substance use among adults who smoke cigarettes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This study investigated the effectiveness of quitline service intensity (high vs. low) on past 30-day tobacco abstinence at 7-months follow-up, using observational data from the Oklahoma Tobacco Helpline (OTH) between April 2020 and December 2021. To assess the impact of loss to follow-up and non-random treatment assignment, we fit the parameters of a marginal structural model to estimate inverse probability weights for censoring (IPCW) and treatment (IPTW) and combined (IPCTW). The Risk Ratio (RR) was estimated using modified Poisson regression with robust variance estimator. Of the 4,695 individuals included in the study, 64% received high-intensity cessation services, and 53% were lost to follow-up. Using the conventional complete case analysis (responders only), high-intensity cessation services were associated with abstinence (RR=1.18; 95 CI: 1.04, 1.34). The effect estimate was attenuated after accounting for censoring (RR=1.14; 95% CI: 1.00, 1.30). After adjusting for both baseline confounding and selection bias via IPTCW, high-intensity cessation services were associated with 1.23 times (95% CI: 1.08, 1.41) the probability of abstinence compared to low-intensity services. Despite relatively high loss to follow-up, accounting for selection bias and confounding did not notably impact quit rates or the relationship between intensity of quitline services and tobacco cessation among OTH participants., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Introduction: Cervical spondylosis in the warfighter is a common musculoskeletal problem and can be career-ending especially if it requires fusion. Head-mounted equipment and increased biomechanical forces on the cervical spine have resulted in accelerated cervical spine degeneration. Current surgical gold standard is anterior cervical discectomy and fusion (ACDF). Posterior cervical foraminotomy (PCF) is a nonfusion surgical alternative, and this can be effective in alleviating radiculopathy from foraminal stenosis caused by disc-osteophyte complex. Biomechanical studies have not been done to analyze motion associated with military aircrew personnel following PCF. The aim of this study was to compare the biomechanical responses of the effects of ACDF and PCF with different grades of facet resection under simulated military aircrew conditions using range of motion, disc pressure, and facet loads at the index and adjacent levels., Materials and Methods: A validated 3D finite element model of the human cervical spinal column was used to simulate various graded PCF and ACDF. All surgical simulations were performed at the most commonly operated level (C5-C6) in warfighters. Pure moment loading under flexion, extension, and lateral bending, and in vivo follower force of 75 N were applied to the intact spine. Hybrid loading protocol was used to achieve 134 degrees of combined flexion-extension and 83 degrees of lateral bending in intact and surgical models to reflect military loading conditions. Segmental motions, disc pressure, and facet load were obtained and normalized with respect to the intact model to quantify the biomechanical effect., Results: Anterior cervical discectomy and fusion decreased range of motion at the index and increased motion at the adjacent levels, while all graded PCF responses had an opposite trend: increased motion at the index and decreased motion at adjacent levels. The magnitude of changes depended on the level of resection, spinal level, and loading mode. Disc pressure increased at the index level and decreased at the adjacent levels after PCF. These changes were exaggerated with increasing extent of facet resection. Facet load increased at the index level after PCF especially with extension and right (contralateral) lateral bending. Complete facetectomy led to facet load increases greater than ACDF at the adjacent levels in both flexion and extension., Conclusions: Posterior cervical foraminotomy is a motion-preserving implant-free surgical alternative to ACDF for warfighters with cervical radiculopathy after failure of conservative management. The treating surgeon must pay close attention to the extent of facet resection to avoid potential spinal instability and future disc and facet degeneration after PCF. Posterior cervical foraminotomy can be more advantageous than ACDF in terms of adjacent segment degeneration, motion preservation, reoperation rate, surgical cost, and retention of warfighters., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Introduction: While the 44-mm clay penetration criterion was developed in the 1970s for soft body armor applications, and the researchers acknowledged the need to conduct additional tests, the same behind the armor blunt trauma displacement limit is used for both soft and hard body armor evaluations and design considerations. Because the human thoraco-abdominal contents are heterogeneous, have different skeletal coverage, and have different functional requirements, the same level of penetration limit does not imply the same level of protection. It is important to determine the regional responses of different thoraco-abdominal organs to better describe human tolerance and improve the current behind armor blunt trauma standard. The purpose of this study was to report on the methods, procedures, and data collected from swine., Materials and Methods: Live swine tests were conducted after obtaining approvals from the local institution and the Army Care and Use Review Office of the U.S. Department of Defense. Trachea tubes and an intravenous line were introduced before administering anesthesia. Pressure transducers were inserted into the lungs and aorta. An indenter simulating the backface deformation profiles produced by body armor from military-relevant ballistics to human cadavers was used to deliver impact loading to the liver region. A triaxial accelerometer was included in the indenter design. The animals were monitored for 6 hours, necropsies were performed, and injuries were identified. Biomechanical data of the energy, velocity, deflection, viscous criterion, force, and impulse variables were obtained for each test., Results: Peak accelerations, velocities, deflections, forces, impulse, and energies ranged from 897 to 5,808 g, 21 to 59 m/s, 1.96 to 8.87 cm, 2.3 to 13.1 kN, 1.1 to 7.1 Ns, and 58 to 387 J, respectively. The peak viscous criterion ranged from 0.8 to 5.8 m/s. All animals survived the 6-hour survival period. Three animals responded with liver lacerations while the remaining 4 did not have any injuries., Conclusion: The experimental design based on parallel tests with whole body human cadavers and cadaver swine was found to be successful in delivering controlled impacts to the liver region of live swine and reproducing liver injuries. Previously used biomechanical measures as potential candidates for injury criteria development were obtained. Using this proven model, tests with additional samples are needed to develop injury risk curves for liver impacts and obtain regional (liver) injury criteria., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: With similar prevalence to injuries from fires, stings, and natural disasters, soft tissue injuries may occur from fireworks, industrial accidents, or other explosives. Surgeons are less familiar with treating high-velocity penetration from small debris, which may increase the chance of infection and subsequent fatality. Penetration risk curves have been developed to predict V50, the velocity with 50% probability of penetration, for various sized projectiles. However, there has been limited research using nonmetallic materials to achieve lower density projectiles less than 1 g cm-2, such as sand or rocks., Material and Methods: To emulate the size and density of these energized particles, 14 ball bearings of stainless steel, silicon nitride, or Delrin acetal plastic ranging from 1.59 mm (1/16") to 9.53 mm (3/8") with sectional densities between 0.3 g cm-2 and 5  g cm-2 were launched toward porcine legs at a range of velocities to determine the penetration thresholds. High-speed videography was captured laterally at 40 kHz and impact velocity was captured using a physics-based tracking software. A generalized linear model with repeated measures and a logit link function was used to predict probability of penetration for each projectile. A total of 600 impacts were conducted to achieve at least 15 penetrating impacts for each projectile over a range of velocities., Results: Higher impact velocities were required to penetrate the skin as sectional density of the projectile decreased, and the relationship between velocity and sectional density exhibited an exponential relationship (V50, $ = 184.6*S{D^{ - 0.385}}$, R2 = 0.95) with substantial change for nonlinearity in sectional densities ranging from 0.3 g cm-2 to 1  g cm-2. Compared to previous studies, the empirical relationship was consistent in the linear region (2-5  g cm-2), and novel experimentation filled in the gaps for sectional densities less than 1  g cm-2, which expressed more nonlinearity than previously estimated. For low-density projectiles with diameters of 1.59 (1/16") or 3.18 (1/8"), 32 impacts were lodged into the epidermis but did not penetrate through the dermis; however, penetration was defined as displacement into or through the dermis., Conclusions: These experimental results may be used to develop and validate finite element simulations of low-density projectile impacts to address complex, multivariate loading conditions for the development of protective clothing to reduce wounding and subsequent infection rates., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Clinical investigations have attributed lumbar spine injuries in combat to the vertical vector. Injury prevention strategies include the determination of spine biomechanics under this vector and developing/evaluating physical devices for use in live fire and evaluation-type tests to enhance Warfighter safety. While biological models have replicated theater injuries in the laboratory, matched-pair tests with physical devices are needed for standardized tests. The objective of this investigation is to determine the responses of the widely used Hybrid III lumbar spine under the vertical impact-loading vector., Materials and Methods: Our custom vertical accelerator device was used in the study. The manikin spinal column was mounted between the inferior and superior six-axis load cells, and the impact was delivered to the inferior end. The first group of tests consisted of matched-pair repeatability tests, second group consisted of adding matched-pair tests to this first group to determine the response characteristics, and the third group consisted of repeating the earlier two groups by changing the effective torso mass from 12 to 16 kg. Peak axial, shear, and resultant forces at the two ends of the spine were obtained., Results: The first group of 12 repeatability tests showed that the mean difference in the axial force between two tests at the same velocity across the entire range of inputs was <3% at both ends. In the second group, at the inferior end, the axial and shear forces ranged from 4.9-25.2 kN to 0.7-3.0 kN. Shear forces accounted for a mean of 11 ± 6% and 12 ± 4% of axial forces at the two ends. In the third group of tests with increased torso mass, repeatability tests showed that the mean difference in the axial force between the two tests at the same velocity across the entire range of inputs was <2% at both ends. At the inferior end, the axial and shear forces ranged from 5.7-28.7 kN to 0.6-3.4 kN. Shear forces accounted for a mean of 11 ± 8% and 9 ± 3% of axial forces across all tests at the inferior and superior ends. Other data including plots of axial and shear forces at the superior and inferior ends across tested velocities of the spine are given in the paper., Conclusions: The Hybrid III lumbar spine when subjected to vertical impact simulating underbody blast levels showed that the impact is transmitted via the axial loading mechanism. This finding paralleled the results of axial force predominance over shear forces and axial loading injuries to human spines. Axial forces increased with increasing velocity suggesting the possibility of developing injury assessment risk curves, i.e., the manikin spine does not saturate, and its response is not a step function. It is possible to associate probability values for different force magnitudes. A similar conclusion was found to be true for both magnitudes of added effective torso mass at the superior end of the manikin spinal column. Additional matched-pair tests are needed to develop injury criteria for the Hybrid III male and female lumbar spines., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: The optimal timing of vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines after cellular therapy is incompletely understood. The objectives of this study are to determine whether humoral and cellular responses after SARS-CoV-2 vaccination differ if initiated <4 months versus 4-12 months after cellular therapy., Methods: We conducted a multicenter, prospective, observational study at 30 cancer centers in the United States. SARS-CoV-2 vaccination was administered as part of routine care. We obtained blood prior to and after vaccinations at up to 5 time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T-cell receptors, in a subgroup., Results: We enrolled 466 allogeneic hematopoietic cell transplantation (HCT) (n = 231), autologous HCT (n = 170), and chimeric antigen receptor T-cell (CAR-T-cell) therapy (n = 65) recipients between April 2021 and June 2022. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months versus 4-12 months after cellular therapy. Anti-S IgG ≥2500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T-cell recipients, respectively. SARS-CoV-2-specific T-cell responses were attained in 57%, 83%, and 58%, respectively. Pre-cellular therapy SARS-CoV-2 infection or vaccination and baseline B-cell count were key predictors of post-cellular therapy immunity., Conclusions: These data support mRNA SARS-CoV-2 vaccination prior to, and reinitiation 3 to 4 months after, cellular therapies with allogeneic HCT, autologous HCT, and CAR-T-cell therapy., Competing Interests: Potential conflicts of interest . J. A. H—research funding: AlloVir, Geovax, Merck; consulting: Pfizer, Gilead, Moderna, Geovax, AlloVir. J. H. Y.—research funding: AlloVir, Ansun, Cidara, F2G, GSK, NobelPharma, Pulmocide, Scynexis, Shire/Takeda. L. W. L.—employment and equity holder in Adaptive Biotechnologies Corporation. M. V. D.—research funding: Janssen, Roche/Genentech. R. N.—consulting: Ono Pharmaceutical, Jazz Pharmaceuticals, Bluebird Bio, Omeros Pharmaceutical, Sanofi, Pfizer. J. M.—consulting: Evision, Kite, Allovir, Bristol Myers Squibb, Novartis, CRISPR, Nektar, Caribiou Bio, Sana Technologies, Legend Biotech. S. D.—research funding: MSK Leukemia SPORE Career Enhancement Program and MSK Gerstner Physician Scholar program. J. J. A.—employment: National Marrow Donor Program; Advisory Board: AscellaHealth, Takeda. M. H.—research support/funding: Takeda Pharmaceutical Company, ADC Therapeutics, Spectrum Pharmaceuticals, Astellas Pharma; consultancy: Incyte Corporation, MorphoSys, SeaGen, Gamida Cell, Novartis, Legend Biotech, Kadmon, ADC Therapeutics, Omeros, AbbVie, Caribou, CRISPR, Genmab, Kite; Speaker’s Bureau: Sanofi Genzyme, AstraZeneca, BeiGene, ADC Therapeutics, Kite; Data Monitoring Committee: Myeloid Therapeutics, Inc. M. L. R.—research funding from Jazz Pharmaceuticals and Atara Bio-Pharma; employment by IQVIA Biotech and Kura Oncology; stock in Kura Oncology. M. M. H.—research funding from Astellas Pharma, CSL Behring, Incyte, Sanofi; consultancy: Sobi, Inc. M.-A. P.—honoraria from Adicet, Allogene, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, ImmPACT Bio, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Sanofi, Syncopation, VectivBio AG, and Vor Biopharma; he serves on Data and Safety Monitoring Boards (DSMBs) for Cidara Therapeutics and Sellas Life Sciences, and the scientific advisory board of NexImmune; he has ownership interests in NexImmune, Omeros, and OrcaBio; he has received institutional research support for clinical trials from Allogene, Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Point-of-care ultrasonography (POCUS) has rapidly evolved from a niche technology to an indispensable tool across medical specialties, including nephrology. This evolution is driven by advancements in technology and the visionary efforts of clinicians in emergency medicine and beyond. Recognizing its potential, medical schools are increasingly integrating POCUS into training curricula, emphasizing its role in enhancing diagnostic accuracy and patient care. Despite these advancements, barriers such as limited faculty expertise and 'lack of' standardized guidelines hinder widespread adoption and regulation. The International Alliance for POCUS in Nephrology (IAPN), through this position statement, aims to guide nephrologists in harnessing the diagnostic power of POCUS responsibly and effectively. By outlining core competencies, recommending training modalities and advocating for robust quality assurance measures, we envision a future where POCUS enhances nephrology practice globally, ensuring optimal patient outcomes through informed, evidence-based decision-making. International collaboration and education are essential to overcome current challenges and realize the full potential of POCUS in nephrology and beyond., Competing Interests: S.A. is supported by ECHONous with a research grant in kind. The remainder of the authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: During infection with the Lyme arthritis (LA) pathogen Borrelia burgdorferi, T-cell responses to both host and pathogen are dysregulated, resulting in chronic infection and frequent development of autoimmunity., Methods: To assess CD4+ T-cell epitopes presented during development of LA, we used an unbiased, immunopeptidomics approach to characterize the major histocompatibility complex (MHC) class II immunopeptidome in B burgdorferi-infected C57BL/6 (B6) mice, which develop mild, self-limiting LA, and infected B6 Il10-/- mice, which develop severe, persistent LA at 0, 4, and 16 weeks postinfection (22-23 mice per group)., Results: Peptides derived from proteins involved in adaptive T- and B-cell responses and cholesterol metabolism, including human Lyme autoantigen apolipoprotein B-100 (apoB-100), were enriched in infected Il10-/- mice; whereas peptides derived from proteins involved in neutrophil extracellular net formation were enriched in infected B6 mice. Presentation of apoB-100 peptides showed evidence of epitope expansion during infection. Of several identified B burgdorferi peptides, only 1, a methyl-accepting chemotaxis protein peptide Mcp4442-462, was immunogenic., Conclusions: ApoB-100, a human Lyme autoantigen, undergoes marked epitope expansion during LA development. The paucity of immunogenic B burgdorferi epitopes supports previous findings suggesting CD4+ T-cell responses are suppressed in murine LA., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Physical activity can improve cognition; however, little is known regarding the relationships between longitudinal objectively-measured physical activity, cognition, and inflammation in older breast cancer survivors., Methods: Older (≥60 yrs) breast cancer survivors (n = 216) and frequency-matched non-cancer controls (n = 216) were assessed at baseline (pre-systemic therapy for survivors) and annually for up to five years. Assessments included hip-worn ActiGraphs worn for seven days, neuropsychological tests, the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI) subscale, and circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6). Data were analyzed using linear mixed-effect, random-effect contemporaneous fluctuation, and multi-level mediation models, considering covariates; p < .05 (two-sided) was considered significant., Results: Survivors had fewer minutes of moderate-to-vigorous physical activity (MVPA) than controls at 36-, 48-, and 60-month time points (p < .03). Fewer survivors met Aerobic Physical Activity Guidelines at 36 months than controls (17.7% vs 33.0%, p = .030). When Guidelines were met (vs not), FACT-Cog PCI scores were 2.1 ± 1.0 (p = .034) points higher. Higher MVPA and meeting Aerobic Guidelines were not related to objective neuropsychological performance. MVPA was inversely associated with CRP and IL-6 (p < .001), but inflammation did not mediate physical activity effects on perceived cognition., Conclusions: Older breast cancer survivors were less physically active than older non-cancer controls, especially farther from baseline. Meeting Aerobic Guidelines was associated with better perceived cognition in survivors. Survivorship care should consider physical activity monitoring and referral to rehabilitation and supervised exercise programs to promote physical activity and improve recovery in older survivors., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Observational research from large population databases may be affected by unmeasured confounding and time-related biases, such as immortal time bias. Modern causal inference practice applies propensity score-based methods, new-user designs, and other strategies to mitigate bias. The degree to which these methodologic approaches adequately address bias for any particular study may be difficult to measure. Recently, the incorporation of positive and negative controls has been identified as a means to assess for the impacts of residual confounding and/or time-related biases. The objective of this commentary is to describe the role of positive and negative controls in observational research. We offer recommendations for incorporating controls into critical appraisal and observational research projects., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Mesenchymal stromal cells (MSCs) are investigated as cellular therapeutics for inflammatory bowel diseases and associated perianal fistula, although consistent efficacy remains a concern. Determining host factors that modulate MSCs' potency including their secretion of angiogenic and wound-healing factors, immunosuppression, and anti-inflammatory properties are important determinants of their functionality. We investigated the mechanisms that regulate the secretion of angiogenic and wound-healing factors and immune suppression of human bone marrow MSCs. Secretory analysis of MSCs focusing on 18 angiogenic and wound-healing secretory molecules identified the most abundancy of vascular endothelial growth factor A (VEGF-A). MSC viability and secretion of other angiogenic factors are not dependent on VEGF-A secretion which exclude the autocrine role of VEGF-A on MSC's fitness. However, the combination of inflammatory cytokines IFNγ and TNFα reduces MSC's VEGF-A secretion. To identify the effect of intestinal microvasculature on MSCs' potency, coculture analysis was performed between human large intestine microvascular endothelial cells (HLMVECs) and human bone marrow-derived MSCs. HLMVECs do not attenuate MSCs' viability despite blocking their VEGF-A secretion. In addition, HLMVECs neither attenuate MSC's IFNγ mediated upregulation of immunosuppressive enzyme indoleamine 2,3-dioxygenase nor abrogate suppression of T-cell proliferation despite the attenuation of VEGF-A secretion. We found that HLMVECs express copious amounts of endothelial nitric oxide synthase and mechanistic analysis showed that pharmacological blocking reverses HLMVEC-mediated attenuation of MSC's VEGF-A secretion. Together these results suggest that secretion of VEGF-A and immunosuppression are separable functions of MSCs which are regulated by distinct mechanisms in the host., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetically determined myocardial atrophy which progressively extends from the epicardium towards the endocardium, resulting in wall thinning. It is one of the leading causes of sudden death in young people. Postmortem studies demonstrate that up to 70-80% of the cases have biventricular involvement. Variable penetrance and expressivity results in a wide phenotypic spectrum, challenging diagnostic accuracy of advanced multimodality imaging tools. Prompt recognition, non-invasive imaging, risk stratification for sudden cardiac death (SCD), and preventive measures are paramount to improve prognosis., Case Summary: Here, we present a 22-year-old Black male who was referred to our electrophysiology clinic with palpitations, remote syncope, and a family history of SCD. Over 3 years, he developed gradually worsening symptomatic palpitations. While physical exam and transthoracic echocardiography were unremarkable, his cardiac magnetic resonance imaging was consistent with biventricular ACM. Genetic testing confirmed ACM, revealing double heterozygosity in DSG2 and PKP2 . Given the elevated estimated risk of life-threatening dysrhythmias, a subcutaneous cardiac defibrillator was successfully implanted., Discussion: Frequently, patients with ACM have more than one mutation in the same gene (compound heterozygosity) or in a second gene (double heterozygosity). Genetic counselling is strongly recommended for family members of the proband. The diagnosis of ACM may be mimicked by other diseases (cardiac sarcoidosis, dilated cardiomyopathy, amyloidosis), thus genetic testing can be useful to determine the presence of the disease. The present report provides an overview of the clinical course, diagnostic criteria, risk stratification, and prognostication for patients with ACM., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)