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Perceptions of high-sensitivity C-reactive protein testing (hsCRP) in atherosclerotic cardiovascular disease: a US survey on cardiologists and nephrologists.
No full textINTRODUCTION: High-sensitivity C-reactive protein (hsCRP) is a biomarker of systemic inflammation (SI) and its elevated level is considered a risk-enhancing factor for cardiovascular disease in primary prevention. This study aimed to understand opinions of US clinicians using hsCRP testing in the management of patients with atherosclerotic cardiovascular disease (ASCVD) with or without chronic kidney disease (CKD).
MATERIALS & METHODS: Clinicians who ordered hsCRP testing with evaluation of patient-level data were surveyed, between June 2023-August 2023. Endpoints included self-identified drivers and barriers to hsCRP testing and assessment of posttest actions following SI recognition.
RESULTS: Common factors perceived to prevent hsCRP testing were a lack of evidence showing improvements in patient cardiovascular outcomes after addressing SI in ASCVD and CKD (50%), and lack of proven efficacy of hsCRP testing (33%). Barriers to hsCRP testing included cost, insurance coverage and patient refusal. The most common reason for not considering SI in clinical decision-making was that it would not affect management of ASCVD. After the first hsCRP testing, an average reduction of hsCRP level is observed, but not lower than 2 mg/L.
CONCLUSIONS: In this limited study sample, perceived limitations of hsCRP testing included insufficient evidence of improved cardiovascular outcomes in patients with ASCVD
Alterations of the composition and spatial organization of the microenvironment following non-dysplastic Barrett\u27s esophagus through progression to cancer.
No full textBarrett\u27s esophagus (BE), a metaplastic condition that is the only known precursor for esophageal adenocarcinoma (EAC), is relatively common, but progression to cancer is infrequent. BE is inflamed but the contribution of the immune system to the carcinogenic process is unknown. To this end, we contrasted non-dysplastic metaplasia of BE patients, captured when they did not progress (non-progressors), did subsequently, but had not yet progressed (pre-progressors) or had already progressed to EAC (progressors). Using spatial multiplexed 56-protein analysis, serial laser capture microdissection (LCM) RNAseq and shallow whole genome sequencing, we identified prooncogenic immune neighbourhoods and dysregulated immune cell populations predictive of subsequent progression to EAC. Indeed, spatial analysis revealed that M1 macrophages, regulatory natural killer (NK) cells, neutrophils and altered ratios of intraepithelial CD4+ and CD8+ lymphocytes typify tumor microenvironmental (TME) changes associated with cancer initiation. Spatially derived cell-to-cell interactions revealed progression-specific immune cell interaction signatures predominantly involving M1 macrophages NK cells and plasma cells. Furthermore, LCM RNAseq analysis identified gene expression \u27hot\u27 signatures enriched in pre-progression and progression samples. Notably, we also observed a correlation between immune cells and copy number alterations in progressor metaplasia. By exposing coordinated changes in the immune cell landscape in patients at high risk of developing EAC, this multi-omic dataset provides novel diagnostic and therapeutic opportunities
What Clinicians Need to Know About Glucagon-like Peptide 1 Agonists.
No full textThe interplay between metabolic health and autoimmune diseases such as psoriasis (PsO) and psoriatic arthritis (PsA) has garnered increasing attention. Obesity, a key feature of metabolic syndrome, exacerbates disease severity in these conditions, prompting the exploration of treatments addressing both the immune system and metabolism. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), primarily used for type 2 diabetes mellitus, have demonstrated benefits beyond glycemic control, including promoting weight loss, improving metabolic health, and potentially modulating immune responses. There is also a dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist with similar and potentially superior capabilities; throughout this manuscript these will be collectively known as GLP-1RA. Recent studies also suggest that GLP-1RAs may help manage PsO and PsA in patients with obesity. These medications may offer dual benefits by reducing inflammation and addressing metabolic abnormalities like insulin resistance and hyperlipidemia. This article reports on a presentation given at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2024 annual meeting underscoring the potential of GLP-1RAs as a therapeutic option, particularly for obese patients with PsO and PsA. Although promising, the evidence supporting GLP-1RAs for treating PsO and PsA remains limited, necessitating further clinical research to evaluate their safety and efficacy
Approaches to overcome the current treatment plateau in immunotherapy.
No full textAfter its practice-changing success, immune checkpoint inhibitors (ICI) have possibly reached a treatment plateau and novel drug candidates are currently being investigated to overcome resistance to ICI including patients who never responded to ICI. With some of the recent failures of novel checkpoint inhibitors, there has been a shift of focus to other modalities such as antibody drug conjugates and radiopharmaceuticals. And skepticism towards novel agents in immunotherapy, including cell therapies, has yet to be replaced by renewed optimism. The combination of ICI with anti-angiogenic agents appeared as a promising new approach to avoid or revert resistance to ICI. Following these encouraging observations, bispecific agents have followed suit and are emerging as possible advancements. Targeting other immune cells, such as macrophages and epigenetic modulation hold additional promise to overcome resistance. Finally, the recent progress in vaccine development may provide a novel approach to selectively activate the global immune system and re-direct its components to reject tumors. Overall, it appears that the full potential of immunomodulators has not yet been fully achieved. Thus, improving the understanding of cancer biology, the interaction with the immune system and identifying patient subsets who might benefit from resetting their immune system continue to be opportunities for oncology drug development
Outcomes with Impella CP in acute myocardial infarction vs heart failure cardiogenic shock: Insights from the Cardiogenic Shock Working Group.
No full textBACKGROUND: Impella CP (Abiomed, Danvers, MA) microaxial flow pumps are commonly used in acute myocardial infarction (AMI) and heart failure (HF) cardiogenic shock (CS). Contemporary data from large, unselected populations are needed to understand differences between these groups.
METHODS: The Cardiogenic Shock Working Group registry enrolls patients with CS at 36 international sites. We analyzed patients with Impella CP enrolled from 2019-2024, categorized by CS etiology and mechanical support device exposure. Baseline characteristics, complications, and outcomes were compared. Outcomes included survival to discharge, native heart survival, and heart replacement therapy. Multivariable analysis was performed to identify predictors of in-hospital mortality and complications.
RESULTS: A total of 1,486 patients with CS (57.9% AMI-CS, 34.9% HF-CS) and Impella CP were analyzed. Patients with HF-CS were younger (60 vs 64 years; p \u3c 0.001) and more likely to have chronic kidney disease (26.4% vs 13.6; p \u3c 0.001) than those with AMI-CS. Impella CP alone was used in 38.3%, CP+ extracorporeal membrane oxygenation in 23.1%, and CP + ≥2 other devices in 20.4%. Acute kidney injury was more common in HF-CS than AMI-CS (66.5% vs 59.7%, p = 0.03) and acute limb ischemia more common in AMI-CS than HF-CS (14.4% vs 11.0%; p = 0.05). Survival to discharge was 53.4% and was higher in HF-CS than AMI-CS (59.7% vs 49.8%; p \u3c 0.001). Those with ≥2 other devices had the lowest survival (43.8%). Total device number was significantly associated with in-hospital mortality, limb ischemia, and bleeding.
CONCLUSIONS: Differences in baseline characteristics, device exposure, and hospital complications between patients with HF-CS and AMI-CS supported by Impella CP may influence outcomes
Impact of hereditary angioedema attacks on health-related quality of life and work productivity.
No full textBackground: Hereditary angioedema (HAE) negatively impacts health-related quality of life (HRQoL). Few studies have characterized impairments to HRQoL, work productivity, and well-being during and following HAE attacks.
Methods: Patients with ≥1 HAE attack in the previous 3 months were recruited by the United States (US) HAE Association (HAEA) to complete an online survey. Respondents were categorized into those who did (Treated Cohort) and did not (Untreated Cohort) manage their last attack with on-demand treatment (OD). Adapted versions of the EuroQol-Five Dimensions-Five Levels (EQ-5D-5L), EuroQol Visual Analogue Scale (EQ VAS), and Work Productivity and Activity Impairment-General Health assessments were used.
Results: Attacks negatively impacted HRQoL and social and physical aspects of well-being in the Treated (N = 94) and Untreated (N = 20) Cohorts. In the Treated Cohort, mean EQ-5D-5L index score was 0.849 Today and 0.568 During the last treated attack, with the latter score indicating substantial impairment in HRQoL. Mean EQ-5D-5L index scores trended lower as time to OD increased, with mean scores of 0.667 for those treating \u3c 1 h and 0.593-0.504 for those treating ≥1 to \u3c 8 h from attack onset. The percentage of patients with mild attacks decreased as time to OD increased (from 50% for those treating \u3c 1 h to 17-33% for those treating ≥1 h from attack onset), and mean EQ-5D-5L index scores decreased as attack severity increased (mild, 0.742; severe, 0.444). Generally, mean EQ VAS scores decreased as time to OD increased, from 60.1 in those treating \u3c 1 h to 53.3 in those treating ≥8 h from attack onset. In the week following attack onset, average levels of absenteeism, presenteeism, and overall work impairment were 15%, 35%, and 39%, respectively. Despite attacks being of milder severity, declines in HRQoL (mean EQ-5D-5L and EQ VAS scores During the last attack : 0.661 and 73.0, respectively) and impairments in work productivity (mean level of absenteeism, presenteeism, and overall work impairment: 12%, 32%, and 36%, respectively) were also observed in the Untreated Cohort.
Conclusions: Late-treated and untreated attacks were associated with reduced HRQoL and work productivity, driven by attack severity. The negative impact of attacks may be reduced by increasing compliance with HAE guidelines (ie, consider OD for all attacks and treat as soon as possible), and by addressing barriers to OD in general and early treatment in particular
Impact of neoadjuvant treatment on functional outcomes after transanal total mesorectal excision (taTME)-a case series.
No full textBACKGROUND: Total mesorectal excision (TME) is known to adversely impact functional outcomes. In a recent Phase II multicenter prospective trial, significant decline in defecatory and sexual function and fecal incontinence-related quality of life (FIQL) was documented following transanal TME (taTME) for rectal cancer, with neoadjuvant treatment (NAT) identified as a predictor of worse function. However, the impact of NAT on baseline function is poorly understood.
METHODS: Patients in a Phase II multicenter trial (NCT03144765) who underwent taTME with or without NAT completed validated functional questionnaires assessing fecal incontinence (FIQL, Wexner), defecatory function (COREFO), urinary function (IPSS), and sexual function (male: IIEF, female: FSFI). Data were collected pre-NAT, post-NAT, 3-4 months after ileostomy closure (FQ1), and 12-18 months post-taTME (FQ2). Paired t-tests or Wilcoxon tests compared scores between timepoints.
RESULTS: Of 71 patients who received NAT, 10 completed both pre- and post-NAT surveys. Median age was 58 years [IQR 48-61], and 7 patients were male. Tumors were located a median 4.75 cm [IQR 4.0-6.0 cm] from the anal verge. Median baseline COREFO score was 38.1 [29.2-49.8], indicating baseline defecatory dysfunction. No significant differences were observed between pre- and post-NAT scores, though FIQL scores demonstrated a trend toward worse incontinence-related quality of life post-NAT (p = 0.06). Postoperatively, Wexner, FIQL, and COREFO worsened from baseline and post-NAT levels, with partial improvement at 18 months post-op, without returning to baseline. No differences were observed in IPSS scores. IIEF scores showed no new erectile dysfunction post-NAT, but low sample size precluded FSFI analysis.
CONCLUSION: Defecatory, urinary, and sexual function were not significantly altered by NAT, though FIQL trends suggest worsening incontinence-related quality of life. Assessment of function and health-related quality of life at baseline and after each phase of therapy may help better inform patients about the impact of multimodal rectal cancer treatment
Impact of comorbidity burden on outcome in patients with cardiogenic shock: A Cardiogenic Shock Working Group analysis.
No full textAIMS: Comorbidity burden is a major determinant of outcomes. Its prognostic impact on cardiogenic shock (CS) across CS subtypes remains insufficiently characterized. We aimed to characterize the prevalence and distribution of comorbidities in CS, assess their impacts on outcomes, and identify high-risk comorbidity patterns in all-cause, acute myocardial infarction-related (AMI-CS) and heart failure-related CS (HF-CS).
METHODS AND RESULTS: Cardiogenic shock patients from the multicentre Cardiogenic Shock Working Group (CSWG) registry (2020-2024) were analysed. We used adjusted logistic regression models to assess the impact of comorbidities individually, in combination, and as a cumulative burden on in-hospital mortality. We developed the Comorbidity Risk Index for Cardiogenic Shock (COMRI-CS) to capture the association between comorbidities and CS mortality. Among 6815 patients (26.5% AMI-CS, 53.6% HF-CS), 6087 (89.3%) presented with ≥1 comorbidity, and 4390 (64.4%) with ≥3 comorbidities. In-hospital mortality increased with comorbidity burden (AMI-CS: 35.4%, 39.6%, 47.1% with 1-3, 4-6, ≥7 comorbidities, respectively; HF-CS: 19.6%, 24.9%, 27.5%, respectively). A high comorbidity burden was independently associated with a 51% higher relative mortality risk in AMI-CS (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.02-2.23, p = 0.037), and a more pronounced increase of 122% in HF-CS (OR 2.22, 95% CI 1.49-3.37, p \u3c 0.001). Distinct high-risk comorbidities and combinations were identified, varying across CS subtypes. With each COMRI-CS point, in-hospital mortality increased by ~5.5%.
CONCLUSIONS: In this large real-world CS cohort, comorbidity burden was highly prevalent, varied across subtypes, and was independently associated with mortality. Integrating chronic conditions into early CS risk stratification may enhance clinical decision-making in CS management
Scaling Remote Patient Care: The Mechanics of a Paradigm Shift in Chronic Disease Management
No full textThe United States is facing a convergence of health care pressures. There is a surge in chronic diseases, with most individuals aged 65 years or older having multiple chronic conditions. There is also a growing deficit of clinicians to care for an aging population, creating access challenges and suboptimal outcomes. While there is a strong desire for health systems to transition to more value-based care contracting, financial constraints and uncertainty create challenges for health systems to commit to this transition at scale. To address these challenges, health systems and clinicians need an effective, scalable solution for chronic disease management with measurable outcomes addressing the Quadruple Aim. Comprehensive remote patient monitoring — coupled with technology-enabled, guideline-directed medical therapy through remote patient care (RPC) — has the potential to fill this gap by enabling continuous, real-time vitals monitoring and timely clinical care outside of the traditional health care environment. Implementing comprehensive RPC is challenging. Health systems must overcome three critical obstacles: (1) Improving clinical outcomes without creating more work for an already overburdened clinical workforce, (2) Creating a scalable program that can be deployed across a multistate health system, and (3) Delivering a financially sustainable model that increases access for all patients, especially rural and underserved populations. To this end, Providence co-developed such a program with Cadence, which provides RPC for patients with hypertension, heart failure, and type 2 diabetes by leveraging a nurse practitioner-led team of multidisciplinary clinicians that act as a fully integrated practice extension for the primary care clinician. Program-eligible patients are identified with a proprietary algorithm for enrollment according to the provider’s discretion. The clinical solution includes virtual visits during which behavioral, lifestyle, and pharmacologic recommendations are made according to national guidelines to optimize patients’ vitals, symptoms, and medications. Patients’ vitals measured at home are also monitored by a clinical team available 24/7/365 to appropriately triage and provide clinical care, as well as address individual patient needs and questions. The program, which is financially supported by fee-for-service remote patient monitoring Current Procedural Terminology codes, operated across four states and nine markets supporting more than 2,500 patients as of the study period, including 37% from rural or underserved areas. Over 19 to 28 months (depending on the chronic condition), the program has shown relative increases in the percentage of patients achieving goal blood pressure (\u3c 140/90 mmHg) by 43% (to 60% from 42%); all four pillars of guideline-directed medical therapy for heart failure with reduced and preserved ejection fraction by 107% (to 31% from 15%) and 300% (to 24% from 6%), respectively; as well as an overall reduction in blood glucose levels for patients enrolled for diabetes. The RPC program also has contributed to reductions in health care costs and utilization, including inpatient admissions