Predictors of developing renal dysfunction following diagnosis of transthyretin cardiac amyloidosis.

BACKGROUND: In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend worsening renal function (wRF) among ATTR-CA patients. OBJECTIVES: This study assesses which characteristics place patients at higher risk for the development of wRF (defined as a drop of ≥10% in glomerular filtration rate [GFR]) within the first year following diagnosis of ATTR-CA. METHODS: We included patients with ATTR-CA (n = 134) evaluated between 2/2016 and 12/2022 and followed for up to 1 year at our amyloid clinic. Patients were stratified into two groups: a group with maintained renal function (mRF) and a group with wRF and compared using appropriate testing. Significant variables in the univariate analysis were included in the multivariable logistic regression model to determine characteristics associated with wRF. RESULTS: Within a follow-up period of 326 ± 118 days, the median GFR% change measured -6% [-18%, +8]. About 41.8% (n = 56) had wRF, while the remainder had mRF. In addition, in patients with no prior history of chronic kidney disease (CKD), 25.5% developed de novo CKD. On multivariable logistic regression, only New York Heart Association (NYHA) class ≥III (odds ratio [OR]: 3.9, 95% confidence interval [CI]: [1.6-9.3]), history of ischemic heart disease (IHD) (OR: 0.3, 95% CI: [0.1-0.7]), and not receiving SGLT-2i (OR: 0.1, 95% CI: [0.02-0.5]) were significant predictors of wRF. CONCLUSION: Our study demonstrated that the development of de novo renal dysfunction or wRF is common following the diagnosis of ATTR-CA. Additionally, we identified worse NYHA class and no prior history of IHD as significant predictors associated with developing wRF, while receiving SGLT-2i therapy appeared to be protective in this population.

Outcomes of Octogenarian Patients Treated with Tafamidis for Transthyretin Amyloid Cardiomyopathy.

Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) benefit from disease-modifying agents such as tafamidis. However, the survival benefit of tafamidis in elderly patients (age ≥80 years) is not reported. This study aimed to assess the survival of patients with ATTR-CM aged 80 years and older who were treated with tafamidis compared with patients aged <80 years. We conducted a retrospective analysis of patients with ATTR-CM who underwent tafamidis treatment, aged 45 to 97 years at the time of diagnosis between January 1, 2008, and May 31, 2021. A total of 484 patients were included, with 208 in the ≥80 years group and 276 in the <80 years group. The cohort was followed up for mortality outcomes, and hazard ratios with 95% confidence intervals were calculated. After a median follow-up of 18.5 months, 72 deaths were recorded in the entire cohort. Kaplan-Meier curves showed no differences in survival probability between the 2 groups at 30 months (p for log-rank test = 0.76). The survival rates for patients aged ≥80 years who underwent treatment at 1, 2, 3, 4, and 5 years were 94.7%, 86.0%, 77.0%, 77.0%, and 38.5%, respectively. The corresponding rates for patients aged <80 years who underwent treatment were 93.2, 84.8, 74.4, 68.2, and 64.6%, respectively. In the multivariable analysis, the hazard ratio (95% confidence interval) of the mortality comparing treatment patients aged ≥80 years with those aged <80 years was 0.81 (0.41 to 1.61). In conclusion, tafamidis treatment is associated with similar reductions in mortality in older and younger patients with ATTR-CM.

The psychedelic effects of cannabis: A review of the literature.

Cannabis and classic psychedelics are controlled substances with emerging evidence of efficacy in the treatment of a variety of psychiatric illnesses. Cannabis has largely not been regarded as having psychedelic effects in contemporary literature, despite many examples of historical use along with classic psychedelics to attain altered states of consciousness. Research into the "psychedelic" effects of cannabis, and delta-9-tetrahydrocannabinol (THC) in particular, could prove helpful for assessing potential therapeutic indications and elucidating the mechanism of action of both cannabis and classic psychedelics. This review aggregates and evaluates the literature assessing the capacity of cannabis to yield the perceptual changes, aversiveness, and mystical experiences more typically associated with classic psychedelics such as psilocybin. This review also provides a brief contrast of neuroimaging findings associated with the acute effects of cannabis and psychedelics. The available evidence suggests that high-THC cannabis may be able to elicit psychedelic effects, but that these effects may not have been observed in recent controlled research studies due to the doses, set, and settings commonly used. Research is needed to investigate the effects of high doses of THC in the context utilized in therapeutic studies of psychedelics aimed to occasion psychedelic and/or therapeutic experiences. If cannabis can reliably generate psychedelic experiences under these conditions, high-THC dose cannabis treatments should be explored as potential adjunctive treatments for psychiatric disorders and be considered as an active comparator in clinical trials involving traditional psychedelic medications.

Cardiovascular Testing in the United States during the COVID-19 Pandemic: Volume Recovery and Worldwide Comparison.

Purpose: To characterize the recovery of diagnostic cardiovascular procedure volumes in U.S. and non-U.S. facilities in the year following the initial COVID-19 outbreak. Materials and Methods: The International Atomic Energy Agency (IAEA) coordinated a worldwide study called the IAEA Noninvasive Cardiology Protocols Study of COVID-19 2 (INCAPS COVID 2), collecting data from 669 facilities in 107 countries, including 93 facilities in 34 U.S. states, to determine the impact of the pandemic on diagnostic cardiovascular procedure volumes. Participants reported volumes for each diagnostic imaging modality used at their facility for March 2019 (baseline), April 2020, and April 2021. This secondary analysis of INCAPS COVID 2 evaluated differences in changes in procedure volume between U.S. and non-U.S. facilities and among U.S. regions. Factors associated with return to prepandemic volumes in the United States were also analyzed in a multivariable regression analysis. Results: Reduction in procedure volumes in April 2020 compared with baseline was similar for U.S. and non-U.S. facilities (-66% vs -71%, P = .27). U.S. facilities reported greater return to baseline in April 2021 than did all non-U.S. facilities (4% vs -6%, P = .008), but there was no evidence of a difference when comparing U.S. facilities with non-U.S. high-income country (NUHIC) facilities (4% vs 0%, P = .18). U.S. regional differences in return to baseline were observed between the Midwest (11%), Northeast (9%), South (1%), and West (-7%, P = .03), but no studied factors were significant predictors of 2021 change from prepandemic baseline. Conclusion: The reductions in cardiac testing during the early pandemic have recovered within a year to prepandemic baselines in the United States and NUHICs, while procedure volumes remain depressed in lower-income countries.Keywords: SPECT, Cardiac, Epidemiology, Angiography, CT Angiography, CT, Echocardiography, SPECT/CT, MR Imaging, Radionuclide Studies, COVID-19, Cardiovascular Imaging, Diagnostic Cardiovascular Procedure, Cardiovascular Disease, Cardiac Testing Supplemental material is available for this article. © RSNA, 2023.

Predictors of Suicidal Ideation During Residential Substance Use Treatment.

Background: Individuals with substance use disorders (SUDs) and co-occurring chronic health and/or psychiatric conditions face unique challenges in treatment and may be at a greater risk for suicidal ideation relative to persons with SUD alone.Methods: In a sample of individuals entering residential SUD treatment in 2019 and 2020 (N = 10,242), we tested adjusted and unadjusted associations between suicidal ideation and (1) psychiatric symptoms and (2) chronic health conditions at treatment intake and during treatment using logistic and generalized logistic models.Results: Over a third of the sample endorsed suicidal ideation at intake, though the prevalence of suicidal ideation decreased during treatment. In both adjusted and unadjusted models, individuals who reported past-month self-harm, those who reported a lifetime suicide attempt, and individuals who screened positive for co-occurring anxiety, depression, and/or posttraumatic stress disorder were at elevated risk of endorsing suicidal ideation at intake and during treatment (P values < .001). In unadjusted models, chronic pain (odds ratio [OR] = 1.51, P < .001) and hepatitis C virus (OR = 1.65, P < .001) were associated with an elevated risk for suicidal ideation at intake, and chronic pain was associated with elevated risk for suicidal ideation during treatment (OR = 1.59, P < .001).Conclusions: Increasing accessibility to integrated treatments (ie, those that address psychiatric and chronic health conditions) for patients experiencing suicidal ideation may be beneficial in residential SUD treatment settings. Developing predictive models to identify those most at risk of suicidal ideation in real time remains a relevant direction for future work.

Clonotypic architecture of a Gag-specific CD8+ T-cell response in chronic human HIV-2 infection.

The dynamics of T-cell receptor (TCR)selection in chronic HIV-1 infection, and its association with clinical outcome, is well documented for an array of MHC-peptide complexes and disease stages. However, the factors that may contribute to the selection and expansion of CD8+ T-cells in chronic HIV-2 infection, especially at the clonal level remain unclear. To address this question, we undertook a detailed molecular characterization of the clonotypic architecture of an HLA-B*3501 restricted Gag-specific CD8+ T-cell response in donors chronically infected with HIV-2 using a combination of flow cytometry, tetramer-specific CD8+ TCR clonotyping, and in vitro assays. We show that the response to the NY9 epitope is hierarchical and narrow in terms of T-cell receptor-alpha (TCRA) and -beta (TCRB) gene usage yet clonotypically diverse. Furthermore, clonotypic dominance in shared origin CTL clones was associated with a greater magnitude of cytokine production and antigen sensitivity at limiting antigen dilution as well as enhanced cross-reactivity for known HIV-2 variants. Hence, our data suggest that effector mobilization and expansion in human chronic HIV-2 infection may be linked to the qualitative features of specific CD8+ T-cell clonotypes, which could have implications for viral control and disease outcome.

Double-blind randomized proof-of-concept trial of canakinumab in patients with COVID-19 associated cardiac injury and heightened inflammation.

Aims: In coronavirus disease 2019 (COVID-19), myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to interleukin-1ß, in patients with COVID-19, myocardial injury, and heightened inflammation. Methods and results: This trial required hospitalization due to COVID-19, elevated troponin, and a C-reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at Day 14, defined as either an improvement of two points on a seven-category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at Day 28. Forty-five patients were randomly assigned to canakinumab 600 mg (n = 15), canakinumab 300 mg (n = 14), or placebo (n = 16). There was no difference in time to clinical improvement compared to placebo [recovery rate ratio (RRR) for canakinumab 600 mg 1.15, 95% confidence interval (CI) 0.46-2.91; RRR for canakinumab 300 mg 0.61, 95% CI 0.23-1.64]. At Day 28, 3 (18.8%) of 15 patients had died in the placebo group, compared with 3 (21.4%) of 14 patients with 300 mg canakinumab, and 1 (6.7%) of 15 patients with 600 mg canakinumab. There were no treatment-related deaths, and adverse events were similar between groups. Conclusion: There was no difference in time to clinical improvement at Day 14 in patients treated with canakinumab, and no safety concerns were identified. Future studies could focus on high dose canakinumab in the treatment arm and assess efficacy outcomes at Day 28.

Diagnosis and Management of Neuropsychiatric Symptoms in Alzheimer's Disease.

PURPOSE OF REVIEW: To explore the most recent developments in the effective diagnosis and treatment of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD). RECENT FINDINGS: The clinical diagnosis of NPS in AD is facilitated by the use of the Neuropsychiatric Inventory (NPI). CT and MRI scans can be useful for detecting structural changes indicating AD. Other promising diagnostic methodologies that are less frequently used in the clinical setting include positron emission tomography (PET) scans for detecting amyloid and blood tests for detecting serum biomarkers. Numerous pharmaceutical agents have been studied for their use in managing NPS, with antipsychotics being popular for managing agitation but also having significant side effects. Non-pharmacological interventions, such as reminiscence therapy and the Describe, Investigate, Create, Evaluate (DICE) approach may be able to provide treatment without such adverse effects. Diagnosing AD and the comorbid NPS remains primarily a clinical endeavor with CT and MRI scans sometimes used, but evidence is amassing for the use of other imaging modalities and different lab tests for convenient and empiric diagnosis of AD to distinguish it from other psychiatric illnesses. The number of pharmacologic treatments for NPS that are safe as well as efficacious remains limited, yet non-pharmacologic interventions have clear clinical utility. In addition to searching for more successful pharmacological treatments, further research should focus on novel diagnostic tests and non-pharmacologic therapies.

Myocardial perfusion imaging in women for the evaluation of stable ischemic heart disease-state-of-the-evidence and clinical recommendations.

This document from the American Society of Nuclear Cardiology represents an updated consensus statement on the evidence base of stress myocardial perfusion imaging (MPI), emphasizing new developments in single-photon emission tomography (SPECT) and positron emission tomography (PET) in the clinical evaluation of women presenting with symptoms of stable ischemic heart disease (SIHD). The clinical evaluation of symptomatic women is challenging due to their varying clinical presentation, clinical risk factor burden, high degree of comorbidity, and increased risk of major ischemic heart disease events. Evidence is substantial that both SPECT and PET MPI effectively risk stratify women with SIHD. The addition of coronary flow reserve (CFR) with PET improves risk detection, including for women with nonobstructive coronary artery disease and coronary microvascular dysfunction. With the advent of PET with computed tomography (CT), multiparametric imaging approaches may enable integration of MPI and CFR with CT visualization of anatomical atherosclerotic plaque to uniquely identify at-risk women. Radiation dose-reduction strategies, including the use of ultra-low-dose protocols involving stress-only imaging, solid-state detector SPECT, and PET, should be uniformly applied whenever possible to all women undergoing MPI. Appropriate candidate selection for stress MPI and for post-MPI indications for guideline-directed medical therapy and/or invasive coronary angiography are discussed in this statement. The critical need for randomized and comparative trial data in female patients is also emphasized.

Discordance Between Appropriate Use Criteria for Nuclear Myocardial Perfusion Imaging From Different Specialty Societies: A Potential Concern for Health Policy.

IMPORTANCE: Appropriate use criteria (AUC) assist health care professionals in making decisions about procedures and diagnostic testing. In some cases, multiple AUC exist for a single procedure or test. To date, the extent of agreement between multiple AUC has not been evaluated. OBJECTIVE: To measure discordance between the American College of Cardiology Foundation (ACCF) AUC and the American College of Radiology (ACR) Appropriateness Criteria for gauging the appropriateness of nuclear myocardial perfusion imaging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study at an academically affiliated Veterans Affairs medical center. Participants were Veteran patients who underwent nuclear myocardial perfusion imaging between December 2010 and July 2011 with rating of appropriateness by the ACCF and ACR criteria. Analysis was performed in March 2015. MAIN OUTCOMES AND MEASURES: The primary outcome was the agreement of appropriateness category as measured by κ statistic. The secondary outcome was a comparison of nuclear myocardial perfusion imaging results and frequency of ischemia across appropriateness categories for the 2 rating methods. RESULTS: Of 67 indications in the ACCF AUC, 35 (52.2%) could not be matched to an ACR rating, 18 (26.9%) had the same appropriateness category, and 14 (20.9%) disagreed on appropriateness. The study cohort comprised 592 individuals. Their mean (SD) age was 62.6 (9.4) years, and 570 of 592 (96.2%) were male. When applied to the patient cohort, 111 patients (18.8%) could not be matched to an ACR rating, 349 patients (59.0%) had the same appropriateness category for the ACR and ACCF methods, and 132 patients (22.3%) were discordant. Overall, the agreement of appropriateness between the 2 methods was poor (κ = 0.34, P < .001). Ischemia was rare among patients rated as "inappropriate" by the ACCF AUC (1 of 39 patients [2.6%]), while ischemia was more common among patients rated as "usually not appropriate" by the ACR Appropriateness Criteria (14 of 80 patients [17.5%]). CONCLUSIONS AND RELEVANCE: Substantial discordance may exist between methods for assessing the appropriateness of advanced imaging tests. Discordance in methods may translate into differences in clinically relevant outcomes, such as the detection of myocardial ischemia.