Citations

AbstractCases of myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD) co‐occurring with neoplasms have been reported. In this international, retrospective cohort study in South Korea and the USA, 16 of 445 (3.6%) patients with MOGAD had concurrent neoplasm within 2 years of MOGAD onset, resulting in a standardized incidence ratio for neoplasm of 3.10 (95% confidence interval [CI], 1.77–4.81; P < 0.001) when compared to the age‐ and country‐adjusted incidence of neoplasm in the general population. However, none of the nine tumor tissues obtained demonstrated MOG immunostaining. The slightly increased frequency without immunohistopathological evidence suggest with true paraneoplastic MOGAD is extremely rare.

ABSTRACTBackgroundThe factors contributing to sustained ventricular arrhythmias (VAs) >30 days after left ventricular assist device (LVAD) implantation are not well‐established.ObjectivesThis study aimed to predict the factors associated with late sustained VAs after LVAD implantation and develop a predictive score to identify patients with an increased risk of late sustained VAs after the procedure.MethodsWe performed a retrospective cohort study on a training cohort of 623 patients and a validation cohort of 157 patients who underwent LVAD implantation at the Mayo Clinic (Rochester, Phoenix, and Jacksonville) from January 1, 2000, to December 30, 2020. Late sustained VAs were defined as ventricular tachycardia (VT) and ventricular fibrillation (VF) occurring >30 days after the LVAD procedure. Detailed chart reviews of the electronic health records within the Mayo Clinic and outside medical records were performed.ResultsA total of 780 patients were included in our study. Late sustained VAs occurred in 30% (n = 232) of the patients. The significant factors associated with late sustained VAs after LVAD were the history of VAs prior to LVAD (34.1% vs. 23.0%, p < 0.01), implantable cardiac defibrillator (ICD) (87.9% vs. 77.6%, p < 0.01) or cardiac resynchronization therapy (CRT) in situ (43.5% vs. 33.6%, p = 0.008), VT ablation prior to LVAD (5.2% vs. 1.8%, p = 0.010), use of amiodarone (49.1% vs. 38.7%, p = 0.007), use of mexiletine (15.5% vs. 5.7%, p < 0.01), and higher left ventricular end‐diastolic diameter (LVEDD) on echocardiography prior to LVAD implantation (71.4 vs. 68.7 mm, p = 0.002). During follow‐up, the patients who developed late sustained VAs after LVAD had lower survival than those who did not (HR = 1.96, 95% CI:156–2.4, p < 0.001). The average time from LVAD to orthotopic heart transplant was longer among late sustained VAs patients (23 vs. 14 months, p < 0.01). The “VIN” risk score was created to identify four risk groups: low (scores 0), intermediate (score 1), high (score 2), and very high (score 3). The rates of late VA's in the training cohort at 1 year were 9.5%, 14%, 18%, and 25% which was almost similar to the risk of late VA's at validation cohort 10%, 12%, 20%, and 63%, respectively.ConclusionsLate sustained VAs occurred in 30% of the patients who received LVAD and were associated with lower survival. The VIN risk score was developed and validated to stratify patients into low, intermediate, high, and very high risk of late sustained VAs.

ABSTRACTIntroductionLung transplantation has been evolving since its inception in 1963. Over recent years, literature has suggested a shift in the perioperative strategy of mechanical support toward extracorporeal membrane oxygenation (ECMO) as the preferred modality of extracorporeal life support (ECLS) in lung transplantation. The Survey of ECLS Application in Lung transplantation (SEAL) was designed to elucidate the current practice patterns of perioperative ECLS within the United States.MethodsIn this cross‐sectional study, a physician from 62 adult lung transplantation centers across the United States of America (USA) was surveyed on their institutional practices regarding the perioperative management of lung transplantation patients, with a focus on mechanical support.ResultsThe survey completion rate was 74% (46/62 eligible institutions). Most transplant centers utilize venoarterial (VA) ECMO (78%, 36/46) and/or venovenous (VV) ECMO (93%, 29/43) as a bridge to lung transplantation. When ECLS is used intraoperatively, 61% of (28/46) responding programs use VA ECMO as their preferred support. All programs use transesophageal echocardiography (TEE) intraoperatively, 85% (33/39) cannulate for ECMO centrally, and 74% (29/39) use a combination of inhaled and intravenous anesthesia while using ECMO intraoperatively. Most programs do not use antifibrinolytic during VA ECMO (62%, 28/45). Anticoagulation management and VA ECMO flows throughout the procedure showed considerable variation.ConclusionData from SEAL illustrates that though there are some practice commonalities within the United States, there is also quite a bit of variability in practice. Multiple dominant practices within the USA are consistent with a recently published International Society of Heart and Lung Transplantation consensus.

ABSTRACT Rituximab, gemcitabine, and oxaliplatin (R‐GemOx) is a commonly used chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL), but there are limited real‐world data. In a multicenter retrospective study from a cohort of eight US academic centers (LEO CReWE), we evaluated 183 patients with R/R DLBCL and high‐grade B cell lymphoma treated with R‐GemOx, including subgroups treated without intent for consolidation with autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T cell therapy ( n = 100), those utilizing R‐GemOx as a bridge to ASCT or CAR T ( n = 83), and those aged 70 and older ( n = 71). Overall response rates (ORRs) for all patients treated with R‐GemOx were 45% with a complete response (CR) rate of 29%. The median event‐free survival (EFS) was 2.3 months, and the median overall survival (OS) was 13.5 months. Patients receiving R‐GemOx without intent for ASCT or CAR T had ORR and CR rates of 33% and 18%, respectively, with median EFS and OS of 2.0 and 9.5 months, respectively. Patients receiving R‐GemOx as a bridge to ASCT or CAR T had ORR and CR rates of 57% and 36%, respectively, with median EFS and OS of 3.5 and 17.4 months, respectively. Patients receiving R‐GemOx aged 70 and older had ORR and CR rates of 53% and 33%, respectively, with median EFS and OS of 2.2 and 13.9 months, respectively. These data provide a benchmark for R‐GemOx in the rapidly evolving landscape of R/R DLBCL therapies.

Abstract Background RSV is a common respiratory infection that causes significant morbidity in SOTR. However, risk factors for complications such as hypoxic respiratory failure, mechanical ventilation, and secondary infections have not been well described. Methods This retrospective, international, multicenter cohort study is actively recruiting SOTR hospitalized with RSV. Here, we analyzed data from Mayo Clinic (Rochester, Florida, Arizona), Miami Transplant Institute, Cleveland Clinic, and Royal Melbourne Hospital between 2016 and 2019. Secondary infection was defined as culture positive infection within 90 days of RSV diagnosis. Whenever appropriate, logistic and Cox regression analysis were conducted to identify risk factors. Survival functions were estimated using the Kaplan-Meier method.Figure 1:Forest plots of multivariable logistic regression models for risk factors for A) hypoxia, B) secondary infections, C) mechanical ventilation. Note: all variables included are the ones statistically significant on univariate analysis. Abbreviations: CI, confidence interval; OR, Odds ratio; LRTI: lower respiratory tract infection. Results 233 SOTRs (58.8% male; median, 61 years), including 77 (49.1%) kidney, 23 (9.9%) liver, 79 (33.9%) lung, and 38 (16.3%) heart transplants (Table). Hypoxic respiratory failure, mechanical ventilation, and secondary infection were seen in 98 (42.1%), 23 (9.9%), and 58 (24.9%) patients, respectively. After multivariate analysis, age &gt;60 years, symptoms and imaging evidence of lower respiratory tract infection (LRTI) were associated with oxygen requirement (Figure 1A); similar results were observed in an analysis of the lung transplant cohort only. Risk factors on multivariate analysis for secondary infection include a history of rejection within six months and mechanical ventilation (Figure 1B). Risk factors for mechanical ventilation included age &gt;60 years and LRTI on imaging (Figure 1C) after multivariate analysis. Seventeen (7.3%) patients died within 90 days of diagnosis. Cox univariate analysis identified age &gt;60 years and LRTI on imaging, secondary infections, mechanical ventilation and hypoxia on admission were associated with higher mortality (Figure 2 and 3).Figure 2:Forest plot with Cox proportional hazards models. Note: only univariate results shown, multivariate not done due to low number of events. Conclusion This multicenter study of SOTR hospitalized with RSV identified older age ( &gt;60 years old) as a risk factor for hypoxic respiratory failure, mechanical ventilation and death. Mechanical ventilation and a history if rejection within six months of RSV were associated with increased risk of secondary infections, identifying them as high-risk that needs close surveillance for this complication.Figure 3:Effects of A) Age older than 60 years old and B) mechanical ventilation on 90 day probability of survival after RSV infection Disclosures Michelle Yong, MBBS, FRACP, MPH, PhD, MSD: Grant/Research Support|MSD: Honoraria|Takeda: Advisor/Consultant Yoichiro Natori, MD, Eurofin/Viracor: Honoraria|Nobel Pharma: Advisor/Consultant

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT. Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75–100 mg) and those not on antiplatelet therapy. The primary outcome was functional independence at 90 days (modified Rankin Scale (mRS), 0–2). Secondary outcomes included excellent functional outcome at 90 days (mRS, 0–1), mortality, and day 1 post-MT National Institutes of Health Stroke Scale (NIHSS) score. Safety outcomes focused on hemorrhagic complications, including symptomatic intracerebral hemorrhage (sICH). Results: Among 1354 patients, 150 were on pre-stroke low-dose aspirin. After applying inverse probability of treatment weighting (IPTW), aspirin use was associated with significantly better functional outcomes (mRS, 0–2: odds ratio (OR) = 1.89, 95% confidence interval (CI) = 1.14 to 3.12) and lower 90-day mortality (OR = 0.56, 95% CI = 0.32 to 1.00). The aspirin group had lower NIHSS scores on day 1 (β = −1.5, 95% CI = −2.8 to −0.27). The sICH rate was not significantly different between the groups (OR = 0.92, 95% CI = 0.60 to 1.43). Conclusions: Pre-stroke low-dose aspirin was associated with improved functional outcomes and reduced mortality in patients with DMVO undergoing MT, without a significant increase in sICH. These findings suggest that low-dose aspirin may be safe and associated with more frequent excellent outcomes for this patient population. Further prospective studies are needed to validate these results and assess long-term outcomes.

ABSTRACT Symmetry refers to properties that remain invariant upon mathematical transformations. The principles of symmetry have guided numerous important discoveries in physics and chemistry but not in biology and medicine. Here, we aim to explore the presence of symmetry relationships at the gene expression level as a mean to distinguish between healthy and disease states. We deployed Learning-Based Invariant Feature Engineering - LIFE, a hybrid machine learning approach implemented with two symmetric invariant feature functions (IFFs) to identify Invariant Feature Genes (IFGs), which are gene pairs whose IFF single-value outputs remain invariant across individual samples in a given biological phenotype. Our multiclass classification results across the transcriptomes of 25 normal organs, 25 cancer types, and blood samples obtained from 4 different types of neurodegenerative diseases revealed the presence of unique phenotype-specific IFGs. We constructed networks using these IFGs (IF-Nets) and intriguingly, we demonstrated that the hubs could serve as information encoders, capable of reconstructing sample-wise expression values in relation to their counterpart genes. More importantly, we found that hubs of cancer IF-Nets were enriched with both approved and clinical trial drugs, highlighting “symmetry breaking” as a novel approach for treating diseases.

Background Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown. Methods This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. Only patients with occlusion of the distal branches (M2 and M3) of the middle cerebral artery territory were included. Unsuccessful MT was defined as a modified Thrombolysis in Cerebral Infarction score of 0–2a. Propensity score matching was used to control for confounders. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0–2 at 90 days after treatment. Multivariable regression analysis was used to assess factors associated with the primary outcome. Results Of 2903 patients screened for eligibility, 532 patients were analyzed (266 per group) after propensity score matching. The MM group had superior functional outcomes, with 32% achieving mRS 0–1 at 90 days compared with 21% in the MT group (P=0.011). Patients in the MM group also had significantly lower rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 16%, P<0.001) and any hemorrhage (18% vs 48%, P<0.001). On multivariable regression, unsuccessful MT was associated with reduced odds of functional independence (OR 0.50, 95% CI 0.29 to 0.85, P=0.011) and increased odds of sICH (OR 4.32, 95% CI 1.84 to 10.10, P<0.001). Mortality rates were similar between groups (27% in MM vs 29% in MT, P=0.73). Conclusion Unsuccessful MT for MeVO was linked to worse outcomes than best MM. These findings highlight the risks of prolonged attempts and emphasize the importance of efficient procedural decision-making to reduce complications and improve patient outcomes.

Background: Underrepresented minority (URM) patients enroll in cancer clinical trials at low rates. We studied the perspectives of health care professionals to better understand the challenges and potential facilitators of recruiting URM patients into clinical trials. Methods: A purposeful sampling approach was utilized to recruit health care professionals and clinical research staff who recruited and cared for URM patients in a therapeutic cancer clinical trial at any Mayo Clinic site, from July 2018 through October 2021.Data were gathered using a semistructured qualitative interviews. Participants were interviewed about the challenges of recruiting URM patients into cancer clinical trials and possible strategies for improving URM patient enrollment. Data were analyzed using a thematic analysis. Results: Of the key themes that emerged from participant interviews ( n = 28), perceived barriers to recruiting URM patients into clinical trials included lack of workforce diversity, underutilization of patient navigators, ineffective community outreach and patient recruitment, restricted access to diverse patient populations, and restrictive clinical trial eligibility criteria. Other barriers reported were lack of insurance and access to care and transportation, low socioeconomic status, and mistrust of health care and research. Strategies suggested for improving the recruitment of URM patients into clinical trials included: diversifying and adding research staff, increasing and improving community outreach and advocacy, partnering with clinics closer to patients, increasing monetary and logistical support for patient participation, creating opportunities that build and enhance trust, and systematically examining and modifying clinical trial eligibility criteria. Conclusions: Our findings reveal barriers that have limited URM patient inclusion in cancer clinical trials and highlight strategies to overcoming these barriers.

Abstract Background Perry syndrome (PS) is a rare and fatal hereditary autosomal dominant neurodegenerative disorder caused by mutations in dynactin ( DCTN1 ). PS brains accumulate inclusions positive for ubiquitin, transactive‐response DNA‐binding protein of 43 kDa (TDP‐43), and to a lesser extent dynactin. Objectives Little is known regarding the contributions of TDP‐43, an RNA binding protein that represses cryptic exon inclusion, in PS. Therefore, we sought to identify the degree of TDP‐43 dysfunction in two regions of PS brains. Methods We evaluated the levels of insoluble pTDP‐43 and TDP‐43‐regulated cryptic RNAs and protein in the caudate nucleus and substantia nigra of 7 PS cases, 12 cases of frontotemporal lobar degeneration (FTLD) with TDP‐43 pathology, and 11 cognitively healthy controls without TDP‐43 pathology. Results Insoluble pTDP‐43 protein levels were detected in PS brains to a similar extent in the caudate nucleus and substantia nigra but lower than those in FTLD brains. The caudate nucleus of PS showed accumulation of eight TDP‐43‐regulated cryptic RNAs ( ACTL6B , CAMK2B , STMN2 , UNC13A , KCNQ2 , ATG4B , GPSM2 , and HDGFL2 ) and cryptic protein (HDGFL2) characteristic of FTLD. Conversely, only one cryptic target, UNC13A , reached significance in the substantia nigra despite similar pTDP‐43 levels. Conclusion We detected TDP‐43 cryptic RNAs and protein in PS caudate nucleus. Given the importance of cryptic exon biology in the development of biomarkers, and the identification of novel targets for therapeutic intervention, it is imperative we understand the consequences of TDP‐43 dysfunction across different brain regions and determine the targets that are specific and common to TDP‐43 proteinopathies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.