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In this study, we investigated the baseline characteristics and "trajectories" of clinical response in men and women after cardiac resynchronization therapy (CRT) implantation. Although women enjoy improved echocardiographic response after CRT compared with men, the kinetics of this response and its relation to functional performance and outcomes are less clear. We identified 592 patients who underwent CRT implantation at our center between 2004 and 2017 and were serially followed in a multidisciplinary clinic. Longitudinal linear mixed effects regression for cardiac response was specified, including interaction terms between time after CRT and sex , and Cox regression models were used to assess differences in all-cause mortality by gender after CRT. Women in our cohort were younger than men, had less frequent ischemic etiology of heart failure (24% vs 60% in men), a shorter QRS (151 vs 161 ms) and more frequent left bundle branch block (77% vs 52%) at baseline. Women had a greater improvement in left ventricular ejection fraction that was evident starting at approximately 1-month after CRT. We did not observe effect modification by gender in New York Heart Association class or 6-minute walk distance after CRT. Although women had improved mortality after CRT, after adjustment for potential confounders, gender was not associated with mortality after CRT. In conclusion, women were more likely to have CRT implantation for left bundle branch block and exhibited improved echocardiographic but not functional response within the first year after CRT. Clinical outcomes after CRT were not associated with gender in adjusted analysis.

BackgroundPatients with lupus erythematosus (LE) are at a heightened risk for clinical events, chiefly heart attacks and strokes, caused by atherosclerotic cardiovascular disease (ASCVD). We recently proposed new guidelines to categorize levels of risk for future ASCVD events specifically in LE patients, with recommendations for management. Here, we assessed the state of current management of ASCVD event risk in light of these new recommendations.MethodsWe studied our entire UPenn Longitudinal Lupus Cohort of patients with cutaneous LE, without or with concurrent systemic LE, for whom we had full access to medical records (n=370, LE-ASCVD Study Cohort, years 2007-2021).ResultsOf our LE-ASCVD Study Cohort, 336/370 (90.8%) had a designated primary-care physician. By the new guidelines, the most recent plasma LDL cholesterol levels were above goal for 252/370 (68.1%) of the Cohort. Two hundred sixty-six (71.9%) had hypertension, which was under- or un-treated in 198/266 (74.4%). Of current smokers, 51/63 (81.0%) had no documented smoking cessation counseling or referrals. Diabetes was generally well-managed, and hypertriglyceridemia was uncommon. Of the Cohort, 254 patients qualified for two widely used online calculators in primary prevention that estimate the risk of an ASCVD event in the next 10 years: the ACC-ASCVD Risk Estimator Plus and QRisk3. We also stratified these 254 patients into the categories of ASCVD event risk we recently defined specifically for LE. Surprisingly, these three methods for estimating ASCVD event risk showed clinically meaningful agreement for only 100/254 (39.4%), i.e., discordance for over 60% that could affect clinical management. The documented rate of ASCVD events in the first 10 years after enrollment was 22.3% (95% CI 16.9%, 27.4%), indicating a high-risk population despite a preponderance of women and a median age at enrollment of only 47 years.ConclusionCutaneous LE patients are under-treated compared with the new guidelines and, accordingly, they experience a substantial burden of ASCVD events. Moreover, it is unclear how to accurately assess future ASCVD event risk in these patients – except that it is high – and this uncertainty may complicate clinical management. Efforts are underway to improve ASCVD event risk estimation and guideline implementation in lupus patients.

Background/aimsTo compare dry eye disease (DED) signs and symptoms between men and women, as well as between premenopausal and postmenopausal women, in the Dry Eye Assessment and Management (DREAM) study.Methods434 women and 101 men self-reported prior medical history and underwent a standardised DED assessment using the Ocular Surface Disease Index, Brief Pain Inventory, Tear Break-Up Time (TBUT)(s), Schirmer’s test 2 (mm/5 min), National Eye Institute-graded lissamine conjunctival staining, corneal staining, meibomian gland dysfunction evaluation and tear osmolarity (mOsms/L) at baseline, 6 months and 12 months. Multivariable linear regression models were used to compare these scores.ResultsWomen experienced significantly worse DED signs than men with lower Schirmer’s test scores (9.27 vs 12.16; pConclusionIn the DREAM study, women experienced more severe DED signs than men. Further, postmenopausal women presented with more severe DED signs than premenopausal women. Elucidating these differences may improve DED diagnosis and provide future direction in understanding sex-related differences in DED.Trial registration numberNCT02128763.

Calciphylaxis is an uncommon but devastating disorder characterized by vascular calcification and subsequent cutaneous tissue necrosis. This results in exquisitely painful and slow healing wounds that portend exceptionally high morbidity and mortality. The diagnosis of this condition can be complicated because there are no conclusive serologic, radiographic or visual signs that this disease is manifesting. The differential of tissue necrosis is broad, and identifying calciphylaxis requires an adroit understanding of the risk factors and physical signs that should raise suspicion of this condition. Reviews on this subject are uncommon and lack directed commentary from disease experts on the best diagnostic approach for patients suffering from this disease. The goal of this article is to update practicing dermatologists on the current standard of care for calciphylaxis.

Introduction: The most common complication of alcohol septal ablation (ASA) is periprocedural high grade AV block (HGAVB). No long-term follow-up of cardiovascular implantable electronic device (CIED) utilization after ASA has been reported. Hypothesis: Pacemaker dependence on long-term follow up can be predicted by ECG or procedural characteristics. Methods: We analyzed all patients with hypertrophic cardiomyopathy who underwent ASA from December 1998 to December 2019 at our institution and received their first CIED within 30 days after ASA for HGAVB. All available follow-up interrogations were reviewed. CIED dependence was defined as ventricular pacing of ≥5%. CIED programming was determined by the patients’ cardiologists' discretion. Results: A total of 103 patients with hypertrophic cardiomyopathy underwent ASA. The average follow up duration was 10.1 years. Within 30 days after ASA, a total 25 patients received a CIED for HGAVB. On long term follow-up 16 patients (64%) were found to be CIED-dependent. Baseline characteristics, including pre and post-ASA ECG, were not significantly different between dependent and non-dependent patients (Table). The only predictor for CIED dependence was >1 ml of alcohol injected during ASA (OR 6.0, p Conclusions: CIED implantation after ASA is common. Almost two thirds of patients who received CIED for postprocedural HGAVB were CIED-dependent on long term follow up. CIED dependence can be predicted by amount of injected alcohol >1 ml during ASA.

The world is rapidly aging, and yet aging is fraught with many difficulties. In particular, the rights of older people to participate fully in cultural life are frequently not met. To help address this issue, we propose an innovative model for intergenerational, participatory music-making between younger people and older people. Specifically, instead of giving traditional, non-participatory performances for older people as is commonly done in nursing homes and other elderly institutions, we advocate for engaging seniors in collective music-making and singing. We believe this kind of collective music-making will better meet the rights of older adults to participate in cultural life and will lead to stronger intergenerational relationships.

It has been widely reported that rooms with larger windows tend to feel more spacious, and previous studies have found a significant impact of the particular external view that a window affords on people’s preferences for its size and shape. However, little is yet well-understood about how what is seen through the window affects either the subjective sense of spaciousness in a room or the apparent metric size of the interior space. We report the results of a two-part experiment with 14 participants that uses HMD-based immersive virtual reality technology to assess the impact of multiple characteristics of outdoor views on both subjective ratings of spaciousness within a room and on action-based judgments of the room size. Across four different outdoor view conditions, spanning day/night and vista distance variations, as well as three different control conditions including the use of frosted glass, substituting a 2D painting for the window, and removing the window altogether, we found no significant differences in participants’ spaciousness ratings. Comparing room size judgments in a subset of the aforementioned conditions, we found a slightly greater underestimation of egocentric distance to the opposing wall when it contained a window onto a distant vista than when the wall was blank, with intermediate results in the case that a painting, rather than a window, was present. We discuss possible explanations for these findings and outline planned follow-up studies.

Background Heart failure (HF) patients with CRT devices are a vulnerable patient population during the Coronavirus Disease 2019 (COVID-19) Pandemic. It is important to develop innovative virtual care models to deliver multidisciplinary care while minimizing the risk of SARS-CoV2 exposure. Objective We aim to provide a description of how HF patients with CRT devices were assessed and managed in our virtual multidisciplinary clinic during the COVID-19 Pandemic. Clinical outcomes between this group of patients seen in virtual clinic and a historical cohort followed by in-person multi-disciplinary clinic prior to the pandemic were compared. Method This is a retrospective cohort study of HF patients with CRT implants who were seen in the virtual multidisciplinary clinic from March 18th, 2020 to May 27th, 2020 (Virtual Visit Group, N = 43). A historical cohort of HF patients with CRT devices seen in the ReACT clinic in person during the same calendar time period in 2019 was used as a control group (In-Person Visit Group, N = 39). Both groups were followed until July 1st of the same calendar year (2020 or 2019) for clinical events. The primary outcome measure was a combined outcome of all-cause mortality and HF- or device-related hospitalizations during follow-up. The secondary outcome measures included patient satisfaction, COVID-19 infection, and other cardiovascular events. Results In the Virtual-Visit Group, 21 patients (48.8%) had their initial ReACT clinic visit (first visit after CRT implant) as a virtual visit; 22 patients (51.2%) had prior in-person ReACT clinic visits before the first virtual visit. During the virtual visits, 12 patients had either potential cardiac symptoms or significant device interrogation findings that required clinical intervention. In post-virtual clinic patient satisfaction survey, all 22 patients surveyed (100%) reported being very satisfied or satisfied with the overall experience of the virtual clinic, and every patient (100%) said they would like to use telemedicine again. During a median follow-up period of 82 days (interquartile range [IQR] 61–96 days), one patient died from pneumonia of unclear etiology at an outside hospital, without documentation of COVID-19 positivity. No patient was hospitalized for HF- or arrhythmia-related complications. No patient was diagnosed with COVID-19. Compared with the In-Person Visit Group, there was no significant increase in mortality or major cardiovascular events in the Virtual-Visit Group (2.3% versus 5.1%, P = 0.60). Conclusions and Relevance Virtual multidisciplinary care was feasible for HF patients with cardiac resynchronization therapy devices and achieved good patient satisfaction. Virtual care was not associated with short-term increase in adverse events for HF patients with CRT device during the COVID-19 Pandemic. This virtual care model could help promote the adoption of digital health methodology for high-risk patients with multiple cardiac comorbidities.

Obesity is a US and global epidemic that exacerbates various cancers including prostate cancer (PC). A recent meta-analysis of men with PC found a 20% increased risk of PC-specific mortality for each 5 kg/m2 increase in BMI. To identify ways to exploit this, we performed an in vivo screen to identify kinases that were causally involved in tumor/growth in obese mice. This resulted in the identification of the AMPK-related kinase SNARK a.k.a NUAK2, a YAP1 target gene and positive feedback regulator by inhibition LATS1 kinase. To identify obesity essential kinases LAPC-4 cells were inoculated with an shRNA library of ~5,000 lentivirus targeting 513 kinases. 5 × 106 cells were grafted to chronically obese mice. Tumors were established to ~200 mm3 and a portion collected for reference. Remaining mice were randomized to continue on ad lib WD or 25% CR diet. Genome-integrated shRNA inserts were amplified using nested barcoded primers and sequenced using Illumina Hi-Seq 2000 and quantified. NAUK2 shRNAs (3 of 10) were significantly depleted in LAPC4 xenograft tumors from mice on a Western diet (WD), but not tumors from mice on an isocaloric 25% calorie-restricted (CR) diet. Analysis of NUAK2 gene expression in human PCs shows NUAK2 expression is higher in PC tissue vs. normal benign. In addition, Cox regression analysis showed that NUAK2 is associated with a 3-fold increased chance of developing metastasis disease in high NUAK2 group. Proteomic data from metastatic PC rapid autopsy biopsies shows NUAK2 phospho-target LATS1 Ser464 is higher in metastatic PCs vs. benign localized prostatic tissues. Western blot analysis of PC cell lines shows NUAK2 is elevated in comparison to primary prostate epithelial cells. To test if NUAK2 is an actionable target in PC cells, we utilized two narrow-spectrum kinase inhibitors from the literature, WZ4003 and HTH-02-006. Pharmacologic inhibition of NUAK2 slows 2D PC cell growth and 3D PC spheroid growth of various PC cell lines with an IC50 range between 1-10 uM, with HTH-02-006 being the more potent. In addition, NUAK2 kinase inhibition with WZ4003 and HTH-02-006 significantly slowed migration and Matrigel invasion of PC3 and DU145 cells. To test if NUAK2 is associated with obesity-enhanced PC progression, we tested NUAK2 inhibition in combination with palmitic acid supplementation. Our preliminary studies show that pharmacologic inhibition of NUAK2 sensitized PC cells to fatty acid-induced cell death. In conclusion, our in vivo shRNA screen identified NUAK2 as an essential kinase for tumors grown in obese mice. NUAK2 expression correlates with worse outcomes in PC and NUAK2 kinase activity is elevated in metastatic vs. localized PCs. Our preliminary data show that pharmacologic inhibition of NUAK2 slows PC cell growth and migration/invasion. Lastly, our preliminary studies show that NUAK2 may lower the threshold for fatty acid-induced toxicity. Together, these preliminary data suggest NUAK2 is a relevant actionable target in PC and may synergize with obese host physiology to slow PC tumor growth. Citation Format: Weiwei Fu, Megan Zhao, Amelia Schirmer, Erick J. Maravilla, Junhee Yoon, Sungyong You, Stephen J. Freedland, Everardo Macias. NUAK2 inhibition for prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B07.

Visual design elements influence the spaciousness of a room. Although wallpaper and stencil patterns are widely used in interior design, there is a lack of research on how these surface treatments affect people’s perception of the space. We examined whether the dominant scale of a wallpaper pattern (i) impacts subjective spaciousness judgments, or (ii) alters action-based measures of a room’s size. We found that both were true: participants reported lower subjective ratings of spaciousness in rooms covered with bolder (larger scale) texture patterns, and they also judged these rooms to be smaller than equivalently-sized rooms covered with finer-scaled patterns in action-based estimates of their egocentric distance from the opposing wall of the room. This research reinforces the utility of VR as a supporting technology for architecture and design, as the information we gathered from these experiments can help designers and consumers make better informed decisions about interior surface treatments.