Citations

Positive inotropic agents have an important role in the management of acute decompensated heart failure patients with reduced cardiac output and poor end-organ perfusion. However, despite their acute hemodynamic benefits, the role of inotropes in the management of chronic advanced heart failure remains limited to palliative therapy or as a bridging strategy to mechanical support or heart transplantation. Milrinone is one of the most common inotropic agents used in advanced heart failure to provide symptomatic relief and improved hemodynamics. This review discusses the current evidence of milrinone’s efficacy, indications, outcomes in advanced heart failure, evidence gap, and future directions.

Many older adults, particularly older women, use over-the-counter supplements for antiaging benefits, including for hair and skin. The supplement industry is unregulated by the Food and Drug Administration, and the interactions between supplements and medications are often overlooked by both patients and physicians. This article discusses the proposed mechanism of action, common misconceptions, possible benefits, and potential side effects of the most commonly used antiaging skin supplements by women, including biotin, nicotinamide, hyaluronic acid, collagen, zinc, vitamin C, vitamin A, vitamin E, and other antioxidants. Supplements may also interfere with common blood tests, such as biotin with the thyroid and troponin cardiac enzyme tests, which patients and their clinicians must be aware of and account for when interpreting lab results. Other supplements, such as zinc, are commonly taken in excess and may result in deficiencies in the absorption of other minerals, such as copper. Over-supplementation of fat-soluble vitamins, such as vitamin A and vitamin E, can result in toxic levels since excess is not excreted in the urine. The clinician caring for older patients’ skin and nails must ask older patients about supplement use and be aware of the potential harms of these supplements in some patients.

Objective Mycophenolate mofetil (MMF) can stabilize or improve lung function in systemic sclerosis–related interstitial lung disease (SSc‐ILD). We hypothesized that combining MMF with pirfenidone (PFD) would produce a significantly more rapid and/or greater improvement in lung function. Methods A randomized (1:1), double‐blind, placebo (PLA)‐controlled phase 2 trial was conducted in SSc‐ILD in which patients received PFD or PLA (801 mg three times daily) along with MMF (1,500 mg twice daily) for 18 months. The primary outcome was change in percent predicted forced vital capacity (FVC‐%). Linear mixed‐effects models assessed treatment differences in a modified intention‐to‐treat population. Results Only fifty‐one of 150 intended subjects (34%) were randomized (MMF+PLA, n = 24; MMF+PFD, n = 27). The FVC‐% improved from baseline to 18 months by 2.24 ± 1.35 (least‐squares mean [LSM] ± SEM) in the MMF+PLA group and 2.09 ± 1.28 in the MMF+PFD group (LSM treatment difference −0.14; P = 0.93). Median time to achieve a ≥3% improvement in FVC‐% was numerically faster in the MMF+PFD versus MMF+PLA group (12.3 vs 17.8 months, respectively), but the difference was not significant ( P = 0.33). For secondary outcomes, only the change over 18 months in the Patient‐Reported Outcomes Measurement Information System 29‐item physical function score, favoring MMF+PFD, reached statistical significance ( P = 0.04). Although other related patient‐reported outcomes (PROs) numerically favored the MMF+PFD group, as did quantitative high‐resolution computed tomography measures of ILD, the differences between groups did not reach statistical significance. Early withdrawals from study medication and adverse events of special interest were numerically greater with MMF+PFD (n = 8 vs 2 and n = 20 vs 7, respectively). Conclusion In this underpowered study, there was no statistically significant treatment difference in overall change in FVC‐% between groups. MMF+PFD was not as well tolerated as MMF+PLA.

Abstract Background Onco-hypertension, the interplay between cancer and hypertension, is an emerging specialty highlighting the bidirectional relationship between carcinogenesis, anticancer therapies, and blood pressure regulation. In Pakistan, data on physicians’ awareness and management of onco-hypertension are limited, yet critical given the rising global burden of cancer (24.5 million new cases; 9.6 million deaths in 2017) and hypertension (7.6 million annual deaths) worldwide. Methods A cross-sectional survey was conducted from May to October 2023 among physicians in oncology, internal medicine, cardiology, and allied specialties across tertiary hospitals, private clinics, and teaching institutions in Pakistan. A self-structured questionnaire, covering sociodemographic, knowledge, attitudes, and clinical practices, was distributed online and in person. Descriptive statistics summarized respondent characteristics, and inferential tests (t-tests, ANOVA) examined associations (p < 0.05). Results Mean respondent age was 37.5 ± 7.8 years; 58% male. Specialty distribution: internal medicine (45%), oncology (16%), cardiology (17%), nephrology (8%), pulmonology (13%), and others (1%). Nearly half (49%) rated their onco-hypertension knowledge as “average,” and 62% reported challenges managing hypertensive cancer patients. Key perceived causes in previously normotensive patients were anxiety (48%) and corticosteroid use (40%). Sixty-three percent sometimes adjusted antihypertensive regimens based on cancer therapies, and 80% endorsed the necessity of interdisciplinary coordination for optimal management. Conclusion Pakistani physicians demonstrate moderate understanding of onco-hypertension with prevalent management challenges. Findings underscore the need for targeted educational initiatives, validated clinical guidelines, and structured interdisciplinary collaboration to improve cardiovascular outcomes in cancer care.

Abstract Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for hematological malignancies, yet its potential to drive lymphomagenesis poses significant clinical concerns. In this study, we investigated the mechanisms underlying CAR T-cell–associated lymphomagenesis in the gastrointestinal (GI) tract on a single case, focusing specifically on the role of integrin α4β7 expression and a predisposing somatic SH2B3 mutation. We observed oligoclonal CAR T cells homing to, and clonally expanding in, the GI tract, with the dominant expanded clone harboring both a pathogenic SH2B3 mutation and a CAR transgene integration within a TFCP2 locus. The clonal CAR T cells subsequently transitioned beyond the GI tract into the peripheral blood, suggesting a potential pathway for systemic dissemination. We found clinical, histological, and molecular evidence demonstrating the efficacy of cyclosporine in reducing the expanded malignant clone and achieving durable clinical remission for more than a year. Our findings highlight the complex interplay between CAR T-cell therapy, preexisting genetic vulnerabilities, and the GI microenvironment, emphasizing the need for vigilant monitoring and tailored therapeutic strategies to address the risks associated with CAR T-cell lymphomagenesis.

ABSTRACT Background Optimal management in patients presenting with persistent atrial fibrillation, cardiomyopathy, and atrial as well as ventricular dyssynchrony with left bundle branch block is unclear. Results and Methods A 67‐year‐old female patient presented with persistent atrial fibrillation, cardiomyopathy with a newly reduced ejection fraction (EF), increased P wave duration on electrocardiogram (ECG) and left bundle branch block. After shared decision making, the patient elected to proceed with Bachman bundle/left bundle branch area pacing plus atrioventricular (AV) node ablation. At 6‐month follow‐up post procedure, a repeat echocardiogram showed normalized atrial size and EF (65%). Device interrogation demonstrated no recurrent atrial fibrillation with the patient off antiarrhythmic and heart failure medical therapy. Conclusions Integrated atrial and ventricular synchronization through Bachmann bundle and left bundle branch area pacing may help break the cycle of dyssynchrony, remodeling, and arrhythmia. In combination with AV node ablation, it may be considered as an alternative treatment option in certain cases after shared decision making.

Objectives: The goals of this study are to assess primary care provider (PCP) knowledge of and attitudes toward pediatric obstructive sleep apnea (OSA), and to identify variations in practice patterns. Design: A cross-sectional survey including the Obstructive Sleep Apnea Knowledge and Attitudes in Children (OSAKA-KIDS) questionnaire was administered to PCPs from August to December 2021. Univariable analyses and multivariable linear regressions were performed to analyze associations between demographics and knowledge, attitudes, and screening frequency. Results: Eighty-two PCPs completed the survey (age 43.4 ± 9.6 years, 69.6% female, 90.2% non-Hispanic White). Specialties included Pediatrics (65.9%) and Family Medicine (32.9%). Respondents answered a mean 84.9 ± 10.7% questions correctly on the knowledge portion. Years in practice, provider training, and academic affiliation were not associated with knowledge scores. Less than half (45.1%) of respondents screened for OSA “most of the time” (32.9%) or “always” (12.2%). Higher screening frequency was associated with clinics with higher Medicaid beneficiaries ( P = .002) and a lower proportion of Black patients ( P = .033). Providers who felt more confident in managing OSA were more likely to screen “most of the time” ( B = 0.532, 95% CI [0.120-0.926], P = .012), or “always” ( B = 0.708, 95% CI [0.129-1.29], P = .017). Conclusion: these results suggest guideline-recommended screening for OSA is low among PCPs. Higher confidence in OSA management was associated with higher screening rates. Further studies on interventions aimed to increase screening and confidence may improve equitable care.