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AbstractBackgroundPartners of persons with mild cognitive impairment (pwMCI) show increased rates of depression and other mental health problems compared to the general population. While dyadic behavioral interventions such as cognitive rehabilitation have shown beneficial effects in reducing caregiver burden, research to date lacks consistent outcome measures and rarely focuses on distressed partners. Therefore, this study explored the longitudinal effect of the Healthy Action to Benefit Independence & Thinking® (HABIT) program on partners with relatively low initial adjustment level. We hypothesized that the HABIT program would improve partner adjustment in those who were distressed.MethodData from 322 pwMCI and partners were utilized from the HABIT IRB research registry. Among them, 240 completed HABIT while 82 served as an untreated control group. Consistent with our previous exploratory factor analysis, a composite partner adjustment score was calculated using the Center for Epidemiologic Studies Depression scale (CES‐D), the REACH Anxiety Inventory Form, and the Quality of Life scale for adults with Alzheimer’s Disease (QOL‐AD). We included partners with an adjustment score below the median of each group to focus on partners with low levels of baseline adjustment. Latent growth curve models were conducted at baseline, 3‐month, 6‐month, and 1‐year follow‐ups to investigate the trajectories of partner adjustment level.ResultIn the low adjustment subsample, no between group difference was found at baseline. An overall improvement in partner adjustment scores was observed only in the treatment group (b = 5.00, p<.001). The slope of change was larger (b = 3.75, p = .016) in the treatment group, indicating a faster improvement in adjustment level in HABIT partners with marginally lower baseline and higher follow‐up scores. This difference in the improvement rates was most evident at the 3‐month follow‐up (t(1, 94) = ‐2.63, p = .010) and gradually reduced in subsequent visits.ConclusionIn partners of those with MCI who have low levels of emotional adjustment, behavioral interventions like HABIT can be beneficial in accelerating improvement in their overall adjustment level and facilitate adaptation to their loved ones’ MCI symptoms compared to untreated controls. Techniques taught in dyadic interventions may serve as protective factors for mental health problems in primary caregivers of pwMCI.

Introduction: Ventricular storms are managed with a combination of antiarrhythmic drugs (AAD) and ablation therapy. This study examines outcomes in patients who required cardiac intensive care unit (CICU) admission for ventricular storms. Methods: A retrospective cohort study was conducted of 200 random adult patients who admitted to the CICU at Mayo Clinic Rochester in 2016-2017 for ventricular storm. Continuous variables were analyzed with the Mann-Whitney U test. Categorical variables were analyzed with Fisher's exact test. Results: Of the 200 patients, 33 (16.5%) patients underwent ablation and AAD therapy for ventricular arrhythmias; 167 underwent AAD therapy alone. The patients in the ablation group were significantly younger (median of 60.3 vs. 72.7, U=1570, p&lt;.001), had a lower Charlson Comorbidity Index (3.56 vs. 5.21, U=1916, p=.005), and a higher BMI (31.6 vs. 28.2, U=2028, p=.032). There was no difference in sex and race (white vs. non-white) between the two groups. The patients in the ablation groups had a significantly lower in-hospital mortality (0% vs. 20%, p=.001) and higher 1-year survival (91% vs. 63%, p=.001). There was no difference in length of stay in the CICU, length of stay in the hospital, or rate of hospital readmission within one year of discharge. Conclusions: Our study indicates that critically ill patients who undergo ablation and AAD for ventricular arrhythmias have decreased mortality compared to patients who underwent AAD therapy alone. More research is needed to elucidate whether this survival benefit is secondary to differences in treatment or baseline comorbidities in the two groups. Table 1: Characteristics and outcomes of patients undergoing ventricular storm treatment. Data is reported either as median or number of occurrences (%). Antiarrhythmic drug (AAD), Charlson Comorbidity Index (CCI), Body Mass Index (BMI), Cardiac Intensive Care Unit (CICU), Length of Stay in days (LOS). * Significance with p values &lt; .05

Introduction: The COVID-19 pandemic imposed significant constraints to delivery of cardiac rehabilitation (CR) with many programs relying on delivery of home-based cardiac rehabilitation (HBCR). We sought to compare the effects of HBCR vs conventional center-based CR (CBCR) on clinical metrics, health-related quality of life, and modifiable risk factors in CR patients. Methods: Retrospective cohort study comparing 511 HBCR patients (March 2020-April 2021; COVID-19 pandemic) and 765 age and sex matched CBCR patients (Jan 2018-Jan2020; immediately pre-pandemic) from the Mayo Clinic Health System. We assessed changes in clinical outcomes before and after CR. HBCR included 12 sessions (one in-person assessment + weekly education and exercise monitoring phone/video calls). Conventional CBCR included 36 sessions (3 sessions per week for 12 weeks). Continuous data were described as mean±SD, and comparisons of change between groups were assessed with linear regression adjusting for baseline value, in complete cases. Results: HBCR and CBCR patients were 65±14 yrs old (68% male) and 65±14 yrs old (67% male) respectively. HBCR patients demonstrated greater improvement in exercise days/week whereas CBCR patients had greater improvement in exercise min/day. HBCR patients had greater improvement in blood glucose with a trend towards greater improvement in non-HDL cholesterol. Both groups demonstrated similar improvement on nutrition, depression, health-related quality of life surveys and total, LDL and HDL cholesterol, as well as HbA1c between the groups. Conclusions: Collecting clinical metrics during the COVID-19 pandemic proved challenging due to the initial closure of out-patient services. For patients in whom data was captured, HBCR appears to be similarly effective at improving several intermediate outcomes compared to CBCR. HBCR may be an effective alternative for improving clinical outcomes in patients who are unable to participate in CBCR.

Introduction: Cardiac sarcoidosis (CS) is a non-ischemic disease which can present with right ventricular (RV) dysfunction, but there is a paucity of research describing RV function and natural history in CS. Methods: We queried a registry of 512 CS patients for those with baseline and follow-up echocardiography (TTE). Demographics, medications, and baseline/follow-up TTE data were collected. RV-pulmonary arterial (RV-PA) coupling was approximated by ratio of tricuspid annular plane systolic excursion to estimated pulmonary artery systolic pressure (TAPSE:ePASP). Results: Our query yielded 343 CS patients with mean age 56y (σ=12y), who were predominantly male (67%) and white (90%) with a median follow-up 4y (interquartile range 4.1y). Most had pulmonary sarcoidosis (68%). Baseline TTE data showed left ventricular ejection fraction 48% (σ=14), abnormal RV function with RV systolic pressure (ePASP) 34 mmHg (σ=11), TAPSE 21mm (σ=5), RV S′ 0.14 m/s (σ=0.07), and RV-PA uncoupling (TAPSE:ePASP 0.69 mm/mm Hg, σ=0.25). Baseline RV function parameters did not differ by pulmonary involvement of sarcoidosis. 92% received immunosuppression and 65% received neurohormonal blockade. In long-term follow-up, the overall cohort demonstrated a trend towards worsening of both RV S’ and RV-PA coupling (P=.02 and P=.003 for linear trend, respectively) but stable ePASP (P=.11). Trends in both non-invasive ePASP and RV-PA coupling were similar in patients with and without pulmonary involvement (P=.48 and P=.79, respectively). Conclusions: In our large CS cohort with extensive follow-up, metrics of RV function and RV-PA coupling are often abnormal at CS diagnosis. Echocardiographic measures of PASP tend to remain stable but markers of RV dysfunction, including RV-PA coupling, tend to worsen throughout the disease course irrespective of pulmonary sarcoidosis. More granular phenotyping of pulmonary hypertension in CS is required to better understand this relationship.

Abstract Purpose: To evaluate the impact of trimodality treatment versus monotherapy or dual therapy for radiation-associated angiosarcoma of the breast (RAASB) after prior breast cancer treatment. Experimental Design: With Institutional Review Board approval, we identified patients diagnosed with RAASB and abstracted data on disease presentation, treatment, and oncologic outcomes. Trimodality therapy included (i) taxane induction, (ii) concurrent taxane/radiation, and then (iii) surgical resection with wide margins. Results: A total of 38 patients (median age 69 years) met inclusion criteria. Sixteen received trimodality therapy and 22 monotherapy/dual therapy. Skin involvement and disease extent were similar in both groups. All trimodality patients required reconstructive procedures for wound closure/coverage, compared with 48% of monotherapy/dual therapy patients (P &lt; 0.001). Twelve of 16 (75%) patients receiving trimodality therapy had a pathologic complete response (pCR). With median follow-up of 5.6 years, none had local recurrence, 1 patient (6%) had distant recurrence, and no patients died. Among 22 patients in the monotherapy/dual therapy group, 10 (45%) had local recurrence, 8 (36%) had distant recurrence, and 7 (32%) died of disease. Trimodality therapy demonstrated significantly better 5-year recurrence-free survival [RFS; 93.8% vs. 42.9%; P = 0.004; HR, 7.6 (95% confidence interval, CI: 1.3–44.2)]. Combining all patients with RAASB regardless of treatment, local recurrence was associated with subsequent distant recurrence (HR, 9.0; P = 0.002); distant recurrence developed in 3 of 28 (11%) patients without local recurrence compared with 6 of 10 (60%) with local recurrence. The trimodality group had more surgical complications that required reoperation or prolonged healing. Conclusions: Trimodality therapy for RAASB was more toxic but is promising, with a high rate of pCR, durable local control, and improved RFS.

Prior to the 1990s, prolonged postoperative intubation and admission to the intensive care unit was considered the standard of care following liver transplantation. Advocates of this practice speculated that this time allowed patients to recover from the stress of major surgery and allowed their clinicians to optimize the recipients’ hemodynamics. As evidence in the cardiac surgical literature on the feasibility of early extubation grew, clinicians began applying these principles to liver transplant recipients. Further, some centers also began challenging the dogma that patients need to be cared for in the intensive care unit following liver transplantation and instead transferred patients to the floor or stepdown units immediately following surgery, a technique known as “fast-track” liver transplantation. This article aims to provide a history of early extubation for liver transplant recipients and offer practical advice on how to select patients that may be able to bypass the intensive care unit and be recovered in a non-traditional manner.

Objectives:Mucosal injury in celiac disease (CD) patients can be patchy, and up to 12% of CD patients can have mucosal changes limited to the duodenal bulb. Hence, recent guidelines recommend obtaining bulb biopsies in addition to distal duodenum. This study aimed to describe a cohort of children with isolated bulb CD and assess the benefit of separating bulb biopsies.Methods:A retrospective chart review between January 2011 and January 2022 at 2 medical centers was conducted. We included children with CD who underwent endoscopy with separated biopsies from the bulb and distal duodenum. A blinded pathologist performed Marsh‐Oberhuber grading on selected cases.Results:We identified 224 CD patients, of which 33 (15%) had histologically confirmed isolated bulb CD. Patients with isolated bulb CD were older at diagnosis (10 vs 8 years; P = 0.03). Median anti‐tissue transglutaminase immunoglobulin A (TTG IgA) level was lower in isolate bulb CD (2.8 vs 16.7 times the upper limit of normal [ULN], P < 0.001). Almost 88% (29/33) of isolated bulb CD patients had an anti‐TTG IgA value of less than 10 times the ULN. Time to anti‐TTG IgA normalization (mean 14 months) was similar between the 2 groups. A pathologist review of diagnostic biopsies could not distinguish between the bulb and distal duodenum biopsies in approximately one‐third of the reviewed samples.Conclusions:Separating bulb from distal duodenum biopsies can be considered during CD diagnosis, particularly in children with anti‐TTG IgA levels less than 10 times the ULN. Larger prospective cohorts are needed to decide whether isolated bulb CD is a unique cohort or an early stage of the conventional CD.

Pathogenic variants in KMT5B , a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM # 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest ( n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B -related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems.

AbstractINTRODUCTIONAt the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias.METHODSThe meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry.RESULTSDuring the 4‐day meeting, presenters illuminated aspects of the cross‐talk between APOE and immunity, with a focus on the roles of microglia, triggering receptor expressed on myeloid cells 2 (TREM2), and components of inflammation (e.g., tumor necrosis factor α [TNFα]).DISCUSSIONThis manuscript emphasizes the importance of diversity in current and future research and presents an integrated view of innate immune functions in Alzheimer's disease as well as related promising directions in drug development.