Deep Learning-Enabled Quantification of 99mTc-Pyrophosphate SPECT/CT for Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR CA) is increasingly recognized as a cause of heart failure in older patients, with 99mTc-pyrophosphate imaging frequently used to establish the diagnosis. Visual interpretation of SPECT images is the gold standard for interpretation but is inherently subjective. Manual quantitation of SPECT myocardial 99mTc-pyrophosphate activity is time-consuming and not performed clinically. We evaluated a deep learning approach for fully automated volumetric quantitation of 99mTc-pyrophosphate using segmentation of coregistered anatomic structures from CT attenuation maps. Methods: Patients who underwent SPECT/CT 99mTc-pyrophosphate imaging for suspected ATTR CA were included. Diagnosis of ATTR CA was determined using standard criteria. Cardiac chambers and myocardium were segmented from CT attenuation maps using a foundational deep learning model and then applied to attenuation-corrected SPECT images to quantify radiotracer activity. We evaluated the diagnostic accuracy of target-to-background ratio (TBR), cardiac pyrophosphate activity (CPA), and volume of involvement (VOI) using the area under the receiver operating characteristic curve (AUC). We then evaluated associations with the composite outcome of cardiovascular death or heart failure hospitalization. Results: In total, 299 patients were included (median age, 76 y), with ATTR CA diagnosed in 83 (27.8%) patients. CPA (AUC, 0.989; 95% CI, 0.974-1.00) and VOI (AUC, 0.988; 95% CI, 0.973-1.00) had the highest prediction performance for ATTR CA. The next highest AUC was for TBR (AUC, 0.979; 95% CI, 0.964-0.995). The AUC for CPA was significantly higher than that for heart-to-contralateral ratio (AUC, 0.975; 95% CI, 0.952-0.998; P = 0.046). Twenty-three patients with ATTR CA experienced cardiovascular death or heart failure hospitalization. All methods for establishing TBR, CPA, and VOI were associated with an increased risk of events after adjustment for age, with hazard ratios ranging from 1.41 to 1.84 per SD increase. Conclusion: Deep learning segmentation of coregistered CT attenuation maps is not affected by the pattern of radiotracer uptake and allows for fully automatic quantification of hot-spot SPECT imaging such as 99mTc-pyrophosphate. This approach can be used to accurately identify patients with ATTR CA and may play a role in risk prediction.

Social disparities in cardiovascular mortality of patients with cancer in the USA between 1999 and 2019.

Background: Temporal trends of the impact of social determinants on cardiovascular outcomes of cancer patients has not been previously studied. Objectives: This study examined social disparities in cardiovascular mortality of people with and without cancer in the US population between 1999 and 2019. Methods: Primary cardiovascular deaths were identified from the Multiple Cause of Death database and grouped by cancer status. The cancer cohort was subcategorized into breast, lung, prostate, colorectal, and haematological. The number of cardiovascular deaths, crude cardiovascular mortality rate, cardiovascular age-adjusted mortality rate (AAMR), and percentage change in cardiovascular AAMR were calculated by cancer status and cancer type, and stratified by sex, race, ethnicity, and urban-rural setting. Results: 17.9 million cardiovascular deaths were analysed. Of these, 572,222 occurred in patients with a record of cancer. The cancer cohort were older and included more men and White racial groups. Regardless of cancer status, cardiovascular AAMR was higher in men, rural settings, and Black or African American races. Cardiovascular AAMR declined over time, with greater reduction in those with cancer (-51.6% vs -38.3%); the greatest reductions were in colorectal (-68.4%), prostate (-60.0%), and breast (-58.8%) cancers. Sex, race, and ethnic disparities reduced over time, with greater narrowing in the cancer cohort. There was increase in urban-rural disparities, which appeared greater in those with cancer. Conclusions: While most social disparities narrowed over time, urban-rural disparities widened, with greater increase in those with cancer. Healthcare plans should incorporate strategies for reduction of health inequality equitable access to cardio-oncology services.

Diagnostic accuracy of bone scintigraphy imaging for transthyretin cardiac amyloidosis: systematic review and meta-analysis.

BACKGROUND: Bone scintigraphy imaging is frequently used to investigate patients with suspected transthyretin cardiac amyloidosis (ATTR-CM). However, the reported accuracy for interpretation approaches has changed over time. We performed a systematic review and meta-analysis to determine the diagnostic accuracy of visual planar grading, heart-to-contralateral (HCL) ratio, and quantitative analysis of SPECT imaging and evaluate reasons for shifts in reported accuracy. METHODS: We performed a systematic review to identify studies of the diagnostic accuracy of bone scintigraphy for ATTR-CM from 1990 until February 2023 using PUBMED and EMBASE. Studies were reviewed separately by two authors for inclusion and for risk of bias assessment. Summary receiver operating characteristic curves and operating points were determined with hierarchical modeling. RESULTS: Out of a total of 428 identified studies, 119 were reviewed in detail and 23 were included in the final analysis. The studies included a total of 3954 patients, with ATTR-CM diagnosed in 1337 (39.6%) patients and prevalence ranging from 21 to 73%. Visual planar grading and quantitative analysis had higher diagnostic accuracy (.99) than HCL ratio (.96). Quantitative analysis of SPECT imaging had the highest specificity (97%) followed by planar visual grade (96%) and HCL ratio (93%). ATTR-CM prevalence accounted for some of the observed between study heterogeneity. CONCLUSIONS: Bone scintigraphy imaging is highly accurate for identifying patients with ATTR-CM, with between study heterogeneity in part explained by differences in disease prevalence. We identified small differences in specificity, which may have important clinical implications when applied to low-risk screening populations.

Ambulatory Pulmonary Artery Pressure Monitoring Reduces Costs and Improves Outcomes in Symptomatic Heart Failure: A Single-Centre Canadian Experience.

Background: Pulmonary artery pressure (PAP) monitoring reduces heart failure (HF) hospitalizations (HFHs) and improves quality of life in New York Heart Association (NYHA) class III HF. We evaluated the impact of PAP monitoring on outcomes and health spending in a Canadian ambulatory HF cohort. Methods: Twenty NYHA III HF patients underwent wireless PAP implantation at Foothills Medical Centre, Calgary, Alberta. Baseline, and 3-, 6-, 9-, and 12-month assessments of laboratory parameters, hemodynamics, 6-minute walk text and Kansas City Cardiomyopathy Questionnaire scores were collected. Healthcare costs 1 year pre- and post-implantation were collected from administrative databases. Results: Mean age was 70.6 years; 45% were female. Results were as follows: an 88% reduction in emergency room visits (P = 0.0009); an 87% reduction in HFHs (P < 0.0003); a 29% reduction in heart function clinic visits (P = 0.033), and a 178% increase in nurse calls (P < 0.0002). Questionnaire and 6-minute walk test scores at baseline vs last follow-up were 45.4 vs 48.4 (P = 0.48) and 364.4 vs 402.8 m (P = 0.58), respectively. Mean PAP at baseline vs follow-up was 31.5 vs 24.8 mm Hg (P = 0.005). NYHA class improved by at least one class in 85% of patients. Mean measurable HF-related spending preimplantation was CAD$29,814 per patient per year and postimplantation was CAD$25,642 per patient per year (including device cost). Conclusions: PAP monitoring demonstrated reductions in HFHs, and emergency room and heart function clinic visits, with improvements in NYHA class. Although further economic evaluation is needed, these results support the use of PAP monitoring as an effective and cost-neutral tool in HF management in appropriately selected patients in a publicly funded healthcare system.

Contexte: La surveillance de la pression artérielle pulmonaire (PAP) réduit les hospitalisations liées à l'insuffisance cardiaque (HIC) et améliore la qualité de vie des patients atteints d'insuffisance cardiaque (IC) de classe III de la New York Heart Association (NYHA). Nous avons évalué l'effet de la surveillance de la PAP sur les résultats et les dépenses en santé dans une cohorte de patients ambulatoires atteints d'IC au Canada. Méthodologie: Vingt patients atteints d'IC de classe III de la NYHA se sont fait implanter un dispositif sans fil de surveillance de la PAP au Foothills Medical Centre, à Calgary, en Alberta. Nous avons évalué les patients au départ et aux mois 3, 6, 9 et 12 en fonction des paramètres de laboratoire, de l'hémodynamique, des scores au test de marche de 6 minutes et au questionnaire de cardiomyopathie de Kansas City. Les coûts liés aux soins de santé un an avant et après l'implantation du dispositif ont été extraits de bases de données administratives. Résultats: L'âge moyen des patients est de 70,6 ans et 45 % sont des femmes. Les résultats vont comme suit : une réduction de 88 % des visites à l'urgence (p = 0,0009); une réduction de 87 % des HIC (p < 0,0003); une réduction de 29 % des visites à une clinique de fonction cardiaque (p = 0,033) et une augmentation de 178 % des appels du personnel infirmier (p < 0,0002). Les scores initiaux au questionnaire et au test de marche de 6 minutes par rapport à ceux du dernier suivi sont respectivement de 45,4 contre 48,4 (p = 0,48) et de 364,4 contre 402,8 m (p = 0,58). La PAP moyenne au départ par rapport au suivi est de 31,5 contre 24,8 mmHg (p = 0,005). La classe de l'IC selon la NYHA s'est améliorée d'au moins une position chez 85 % des patients. Les dépenses mesurables moyennes liées à l'IC avant l'implantation sont de 29 814 $ CA par patient par année et de 25 642 $ CA par patient par année après l'implantation (incluent le coût du dispositif). Conclusions: La surveillance de la PAP entraîne une réduction des HIC ainsi que des visites à l'urgence et à la clinique de fonction cardiaque, et une amélioration de la classe de l'IC selon la NYHA. Bien qu'une évaluation économique plus approfondie soit nécessaire, ces résultats militent en faveur de la surveillance de la PAP comme outil de prise en charge de l'IC sans incidence sur les coûts chez les patients adéquatement choisis dans un système de soins de santé financé par les fonds publics.

Prevalence, incidence and clinical outcomes of epicardial coronary artery disease among transthyretin amyloidosis cardiomyopathy patients.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients are often older and may be at risk for obstructive epicardial coronary artery disease (oeCAD). While ATTR-CM may cause small vessel coronary disease, the prevalence and clinical significance of oeCAD is not well described. METHODS AND RESULTS: The prevalence and incidence of oeCAD and its association with all-cause mortality and hospitalization among 133 ATTR-CM patients with ≥ 1-year follow-up was evaluated. The mean age was 78 ± 9 years, 119 (89%) were male, 116 (87%) had wild-type and 17 (13%) had hereditary subtypes. Seventy-two (54%) patients underwent oeCAD investigations, with 30 (42%) receiving a positive diagnosis. Among patients with a positive oeCAD diagnosis, 23 (77%) were diagnosed prior to ATTR-CM diagnosis, 6 (20%) at the time of ATTR-CM diagnosis, and 1 (3%) after ATTR-CM diagnosis. Baseline characteristics between patients with and without oeCAD were similar. Among patients with oeCAD, only 2 (7%) required additional investigations, intervention or hospitalization after ATTR-CM diagnosis. After a median follow-up of 27 months there were 37 (28%) deaths in the study population, including 5 patients with oeCAD (17%). Fifty-six (42%) patients in the study population required hospitalization, including 10 patients with oeCAD (33%). There was no significant difference in the rates of death or hospitalization among ATTR-CM patients with and without oeCAD, and oeCAD was not significantly associated with either outcome by univariable regression analysis. CONCLUSIONS: While oeCAD is prevalent in ATTR-CM patients, this diagnosis is frequently known at time of ATTR-CM diagnosis and characteristics are similar to patients without oeCAD.

Outcomes of ST elevation myocardial infarction in patients with cancer: a nationwide study.

AIMS: To assess processes of care and clinical outcomes in cancer patients with ST elevation myocardial infarction (STEMI) according to cancer type. METHODS AND RESULTS: This is a national population-based study of patients admitted with STEMI in the UK between January 2005 and March 2019. Data were obtained from the National Heart Attack Myocardial Infarction National Audit Project (MINAP) registry and the Hospital Episode Statistics registry. We identified 353 448 STEMI-indexed admissions between 2005 and 2019. Of those, 8581 (2.4%) had active cancer. Prostate cancer (29% of STEMI patients with cancer) was the most common cancer followed by haematologic malignancies (14%) and lung cancer (13%). Cancer patients were less likely to receive invasive coronary revascularization (60.0% vs. 71.6%, P < 0.001] and had higher in-hospital death [odd ratio (OR) 1.39, 95% confidence interval (CI) 1.25-1.54] and bleeding (OR 1.23, 95% CI 1.03-1.46). Cancer patients had higher mortality at 30 days (HR 2.39, 95% CI 2.19-2.62) and 1 year (HR 3.73, 95% CI 3.58-3.89). Lung cancer was the cancer associated with the highest risk of death in the hospital (OR 1.75, 95% CI 1.39-2.22) and at 1 year (OR 8.08, 95% CI 7.44-8.78). Colon cancer (OR 1.98, 95% CI 1.24-3.14) was the main cancer associated with major bleeding. All common cancer types were associated with higher mortality at 1 year. Cardiovascular death (62%) was the main cause of death in the first 30 days, while cancer (52%) was the main cause of death within 1 year. CONCLUSION: STEMI patients with cancer have a higher risk of short- and long-term mortality, particularly lung cancer. Colon cancer is the main cancer associated with major bleeding. Cardiovascular disease was the main cause of death in the first month, whereas cancer was the main cause of death within 1 year.

IL-6 evoked biochemical changes in prostate cancer cells.

The pro-inflammatory cytokine IL-6 has been associated with the progression of PCa to a castration-resistant phenotype. In this work, we characterized the biochemical changes evoked by IL-6 in three different models of PCa cells, including LNCaP, C4-2, and PC3. The effect of IL-6 on PCa cells was compared with the effect obtained by co-stimulation with the cAMP-inducing agent forskolin (FSK). Stimulation of LNCaP cells with IL-6 or IL-6 + FSK evoked increased expression of the neuroendocrine marker tubulin IIIß and Cav3.2 T-type Ca2+ channel subunit. PC3 cells, representing a more advanced state of PCa, had high levels of tubulin IIIß expression without any further changes observed by treatment with IL-6 or IL-6 + FSK. Elevated expression of the glucocorticoid receptor was observed in PC3, but not in LNCaP or C4-2 cells. Glucocorticoid receptor expression was not regulated by IL-6 stimulation of LNCaP or C4-2 cells. IL-6 acting alone or together with FSK evoked a significant reduction in the expression of the transcription factor REST and retinoblastoma tumor suppressor protein Rb1. In LNCaP cells, IL-6 acting alone or together with FSK had no effect on the expression of several biological markers of advanced PCa, including Aurora kinase A, valosin-containing protein, calcium-sensing receptor, calreticulin, S100A protein, and Protein S. In PC3 cells, co-treatment with IL-6 + FSK evoked increased expression of REST and S100A proteins, as well as a reduction in Protein S levels. These findings reveal a complex pattern of biochemical changes in PCa cells under the influence of IL-6.

Hot spot imaging in cardiovascular diseases: an information statement from SNMMI, ASNC, and EANM.

This information statement from the Society of Nuclear Medicine and Molecular Imaging, American Society of Nuclear Cardiology, and European Association of Nuclear Medicine describes the performance, interpretation, and reporting of hot spot imaging in nuclear cardiology. The field of nuclear cardiology has historically focused on cold spot imaging for the interpretation of myocardial ischemia and infarction. Hot spot imaging has been an important part of nuclear medicine, particularly for oncology or infection indications, and the use of hot spot imaging in nuclear cardiology continues to expand. This document focuses on image acquisition and processing, methods of quantification, indications, protocols, and reporting of hot spot imaging. Indications discussed include myocardial viability, myocardial inflammation, device or valve infection, large vessel vasculitis, valve calcification and vulnerable plaques, and cardiac amyloidosis. This document contextualizes the foundations of image quantification and highlights reporting in each indication for the cardiac nuclear imager.

Amyloidosis and COVID-19: experience from an amyloid program in Canada.

Severe acute respiratory syndrome coronavirus (SARS-CoV2) and associated COVID-19 infection continue to impact patients globally. Patients with underlying health conditions are at heightened risk of adverse outcomes from COVID-19; however, research involving patients with rare health conditions remains scarce. The amyloidoses are a rare grouping of protein deposition diseases. Light-chain and transthyretin amyloidosis are the most common disease forms, often present with systemic involvement of vital organs including the heart, nerves, kidneys, and GI tracts of affected individuals. The Amyloidosis Program of Calgary examined 152 ATTR patients and 103 AL patients analyzing rates of vaccination, COVID-19 testing, infection outcomes, influence referrals, and excess deaths. Results showed 15 total PCR-confirmed COVID-19 infections in the tested population of amyloid patients, with a higher frequency of infections among patient with AL compared to the ATTR cohort (26.2% vs 5.1%). Four patients (26.6%) required hospital admission for COVID-19 infection, 2 ATTR, and 2 AL patients. Of the confirmed cases, 1 (0.07%) unvaccinated ATTR patient died of a COVID-19 infection. An excess of deaths was found in both the ATTR and AL cohorts when comparing pre-pandemic years 2018 and 2019 to the pandemic years of 2020 and 2021. The finding suggests that amyloidosis patients are likely at a high risk for severe COVID-19 infection and mortality, especially those of advanced age, those on an active treatment with chemotherapy, and those with concomitant B-cell or plasma cell disorder. The impact of virtual healthcare visits and pandemic measures on the excess of deaths observed requires further research.

Preparation of geranium oil formulations effective for control of phenotypic resistant cattle tick Rhipicephalus annulatus.

The aim of the present study was to evaluate in vitro and in vivo the acaricidal activity of two forms of geranium (Pelargonium graveolens) (PG). These two forms were the P. graveolens essential oil nanoemulsion (PGN), and the PG in combination with the sesame oil (SO), PGSO). These forms were first evaluated in vitro for their adulticidal, ovicidal, and larvicidal activities against the different stages of acaricide-resistant Rhipicephalus annulatus (Say). Geranium nanoemulsion was prepared and then characterized by UV-Vis spectrophotometer, and zeta droplet size measurement. The results revealed that LC50 of the PG against the adult ticks was attained at concentration of 7.53% while it was decreased to 1.91% and 5.60% for PGSO and PGN, respectively. Also, the LC50 of PGN and PGSO were reached at concentrations of 1.688 and 0.944%, respectively against the larvae while the LC50 of the PG was reached at concentration of 3.435% for. The combination of PGN with PG exhibited non-significant ovicidal effect meanwhile PGSO showed significant ovicidal effect even at the low concentration (2.5%). The PGSO and PGN formulations were applied in a field trial to control the ticks of the naturally infested cattle. PGSO and PGN significantly reduced the tick burden to 74.83% and 87.97%, respectively at 3 weeks post-application with performance better than the deltamethrin (29.88%). In conclusion, the two PG forms can be used as suitable alternatives to control R. annulatus tick and they need further modifications for effective field application.

Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.

AIMS: We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site. METHODS AND RESULTS: We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%). CONCLUSION: We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.

Influence of offshore oil and gas structures on seascape ecological connectivity.

Offshore platforms, subsea pipelines, wells and related fixed structures supporting the oil and gas (O&G) industry are prevalent in oceans across the globe, with many approaching the end of their operational life and requiring decommissioning. Although structures can possess high ecological diversity and productivity, information on how they interact with broader ecological processes remains unclear. Here, we review the current state of knowledge on the role of O&G infrastructure in maintaining, altering or enhancing ecological connectivity with natural marine habitats. There is a paucity of studies on the subject with only 33 papers specifically targeting connectivity and O&G structures, although other studies provide important related information. Evidence for O&G structures facilitating vertical and horizontal seascape connectivity exists for larvae and mobile adult invertebrates, fish and megafauna; including threatened and commercially important species. The degree to which these structures represent a beneficial or detrimental net impact remains unclear, is complex and ultimately needs more research to determine the extent to which natural connectivity networks are conserved, enhanced or disrupted. We discuss the potential impacts of different decommissioning approaches on seascape connectivity and identify, through expert elicitation, critical knowledge gaps that, if addressed, may further inform decision making for the life cycle of O&G infrastructure, with relevance for other industries (e.g. renewables). The most highly ranked critical knowledge gap was a need to understand how O&G structures modify and influence the movement patterns of mobile species and dispersal stages of sessile marine species. Understanding how different decommissioning options affect species survival and movement was also highly ranked, as was understanding the extent to which O&G structures contribute to extending species distributions by providing rest stops, foraging habitat, and stepping stones. These questions could be addressed with further dedicated studies of animal movement in relation to structures using telemetry, molecular techniques and movement models. Our review and these priority questions provide a roadmap for advancing research needed to support evidence-based decision making for decommissioning O&G infrastructure.

Quantitative technetium pyrophosphate and cardiovascular magnetic resonance in patients with suspected cardiac amyloidosis.

BACKGROUND: Quantitation of myocardial 99m Tc-pyrophosphate activity may have high diagnostic accuracy, but its correlation with disease burden is unknown. We examined the relationship between 99m Tc-pyrophosphate quantitation and cardiac magnetic resonance (CMR) measures in patients with suspected transthyretin cardiac amyloidosis (ATTR-CM) or light chain cardiac amyloidosis (AL-CM). METHODS: Consecutive patients who underwent 99mTc-pyrophosphate imaging and CMR were included. ATTR-CM and AL-CM were diagnosed using standard criteria. 99mTc-pyrophosphate images were assessed with standard parameters and quantified with cardiac pyrophosphate activity (CPA) and volume of involvement (VOI). We assessed the association between 99mTc-pyrophosphate image interpretation and CMR tissue characteristics. RESULTS: Seventy patients were identified, mean age 70.4 ± 11.4 years, with ATTR-CM and AL-CM diagnosed in 22 (31%) and 11 (16%) patients, respectively. In patients with ATTR-CM, there were significant correlations between CPA (r2 = 0.509, P < 0.001) and VOI (r2 = 0.586, P < 0.001) with native myocardial T1 mapping values. Additionally, CPA (adjusted hazard ratio (aHR) 1.04, P = 0.016), VOI (aHR 1.12, P = 0.034), and average myocardial T1 (aHR 1.12, P = 0.025) were associated with incidence of heart failure hospitalization or death. CONCLUSION: CPA and VOI were correlated with CMR measures of myocardial fibrosis in patients with ATTR-CM. 99mTc-pyrophosphate quantitation may have a role in ATTR-CM disease staging, guiding treatment, or following response to therapy.

IL-6R/Signal Transducer and Activator of Transcription 3 Signaling in Keratinocytes rather than in T Cells Induces Psoriasis-Like Dermatitis in Mice.

Signal transducer and activator of transcription 3 (STAT3) is important for psoriasis pathogenesis because STAT3 signaling downstream of IL-6, IL-21, IL-22, and IL-23 contributes to T helper type 17 cell development and because transgenic mice with keratinocyte (KC) STAT3 expression (K14-Stat3C mice) develop psoriasis-like dermatitis. In this study, the relative contribution of STAT3 signaling in KCs versus in T cells was evaluated in the imiquimod model of psoriasis-like dermatitis. Mice with STAT3-inducible deletion in KCs (K5-Stat3-/- mice) had decreased psoriasis-like dermatitis and epidermal STAT3 phosphorylation compared with wild-type mice, whereas mice with constitutive deletion of STAT3 in all T cells were similar to wild-type mice. Interestingly, mice with KC-inducible deletion of IL-6Rα had similar findings to those of K5-Stat3-/- mice, identifying IL-6/IL-6R as a predominant upstream signal for KC STAT3-induced psoriasis-like dermatitis. Moreover, psoriasis-like dermatitis inversely associated with type 1 immune gene products, especially CXCL10, whereas CXCL10 limited psoriasis-like dermatitis, suggesting that KC STAT3 signaling promoted psoriasis-like dermatitis by restricting downstream CXCL10 expression. Finally, treatment of mice with the pan-Jak inhibitor, tofacitinib, reduced psoriasis-like dermatitis and epidermal STAT3 phosphorylation. Taken together, STAT3 signaling in KCs rather than in T cells was a more important determinant for psoriasis-like dermatitis in a mechanism that involved upstream KC IL-6R signaling and downstream inhibition of type 1 immunity‒associated CXCL10 responses.

Donor and Recipient Size Matching in Heart Transplantation With Predicted Heart and Lean Body Mass.

Donor and recipient size matching during heart transplant can be assessed using weight or predicted heart mass (PHM) ratios. We developed sex-specific allomteric equations for PHM and predicted lean body mass (PLBM) using the United Kingdom Biobank (UKB) and evaluated their predictive value in the United Network of Organ Sharing database. Donor and recipient size matching was based on weight, PHM and PLBM ratios. PHM was calculated using the Multiethnic Study of Atherosclerosis and UKB equations. PLBM was calculated using the UKB and National Health and Nutrition Examination Survey equations. Relative prognostic utility was compared using multivariable Cox analysis, adjusted for predictors of 1-year survival in the Scientific Registry of Transplant Recipients model. Of 53,648 adult patients in the United Network of Organ Sharing database between 1996 and 2016, 6528 (12.2%) died within the first year. In multivariable analysis, undersized matches by any metric were associated with increased 1-year mortality (all P < 0.01). Oversized matches were at increased risk using PHM or PLBM (all P < 0.01), but not weight ratio. There were significant differences in classification of size matching by weight or PHM in sex-mismatched donor-recipient pairs. A significant interaction was observed between pulmonary hypertension and donor undersizing (hazard ratio 1.15, P = 0.026) suggesting increased risk of undersizing in pulmonary hypertension. Donor and recipient size matching with simplified PHM and PLBM offered an advantage over total body weight and may be more important for sex-mismatched donor-recipient pairs. Donor undersizing is associated with worse outcomes in patients with pulmonary hypertension.