Citations

Background: Individual symptoms are predictors of mortality in adults with heart failure (HF). However, symptom clusters may be more predictive of future risks than isolated symptoms, yet research on these symptom clusters in older adults with HF is limited. Aims: To explore the extent to which symptom cluster profiles predict all-cause mortality among community-dwelling older adults with HF, while adjusting for known risk factors. Methods: We conducted a secondary analysis of data of the 2008 to 2016 surveys of the U.S. Health and Retirement Study using latent class analysis to identify baseline cluster profiles, and survival analysis for time to death with Cox proportional hazard (Cox PH) models, and Kaplan Meier survival analyses. Results: We included 684 participants [mean age=74.9, (SD=10) years, 56.6% female, 16.2% Black/African American]. Three baseline symptom cluster profiles were identified: high-burden (pain, shortness of breath, fatigue, swelling, depressive symptoms, dizziness), low-burden, and cardiopulmonary-depressive (shortness of breath, pain, and dizziness). The estimated median time-to-death was 71 (95% CI=64, 79) months. Of the 364 participants in the cardiopulmonary-depressive profile, 240 (65.9%) died (median time= 65 months, 95% CI= 55, 73) compared to those in the low-burden profile, of which 49% died. Approximately 61% in the high burden profile died (median time=67 months, 95% CI= 51, 90). A significant difference in survival times between the 3 cluster profiles was found (Log-rank= 9.13, p = 0.01). In the adjusted Cox PH model, participants in the high symptom burden and respiratory-depressive distress profiles had adjusted HR of 1.48 (95% CI=1.15, 1.94) and 1.44 (95% CI=1.14, 1.80) compared to those in the low burden symptom cluster profile, after controlling for age, gender, smoking, and comorbidities. Conclusions: The identified symptom cluster profiles predict 8-year all-cause mortality in older adults with HF, after controlling for known risk factors. An evaluation of symptom clusters, rather than individual symptoms, may provide additive prognostic information.

Abstract Von Hippel-Lindau (VHL) disease is caused by pathogenic variants in the VHL gene. Abnormal function of VHL protein leads to accumulation of HIF-α and the engagement of hypoxia-sensitive genes with oncogenic effects. VHL is associated with tumors in multiple organs. Belzutifan is an oral selective inhibitor of hypoxia-inducible factor 2 alpha. Belzutifan was approved in 2021 as a targeted therapy for VHL-associated CNS hemangioblastomas, renal cell carcinomas, and pancreatic neuroendocrine tumors. Here, we report on our institutional clinical experience with belzutifan for VHL-associated CNS hemangioblastomas. From October 2021 to May 2024, thirteen adults (9 female, 4 male, median age 40) were treated. Median duration of therapy was 24 months. Seven had a partial radiographic response after median of 3 months; one patient had a partial response; 1 patient had progressive disease on belzutifan. Four patients have been taking belzutifan for less than 3 months, and do not have follow-up imaging to assess response. The most common adverse effect was fatigue (7 patients). Four patients experienced anemia and 2 experienced hypoxia. Three patients discontinued belzutifan due to adverse effects. One patient had to take multiple medication pauses, due to seizure and kidney injury, but resumed treatment with dose reduction. Nine patients remain on therapy. Based on this data, belzutifan is often well-tolerated and associated with durable radiographic responses. Toxicity profile among our patients was similar to that encountered in the clinical trial leading to approval of the agent. These findings provide real-world data supporting continued use of belzutifan in this patient population, with an awareness of potential adverse reactions. Future studies should assess continued radiographic response, sex differences, and effects after long-term use.

Objective To compare cochlear implant (CI) speech perception outcomes in patients with sporadic vestibular schwannoma (VS) managed with observation, radiosurgery, or microsurgery. Study Design Retrospective review. Setting Eleven tertiary academic medical centers. Patients One hundred patients with sporadic VS who received an ipsilateral CI. Interventions Ipsilateral cochlear implantation. Main Outcome Measures Pure-tone thresholds, monosyllabic speech perception testing scores, and rates of open-set speech acquisition. Results Of the 100 patients studied, 54 underwent microsurgery, 26 underwent radiosurgery, 19 continued observation, and 1 underwent multimodal therapy. Among all patients, the median post-implantation pure-tone average was 31 dB (interquartile range [IQR] 25–39 dB) and the median monosyllabic speech perception score was 30% (IQR 0–60%) at a median of 12 months (IQR 5–25 months) post-implantation. Patients who were managed with microsurgery (median speech perception score 11%, IQR 0–52%) exhibited poorer implant outcomes overall compared with those managed with observation (median speech perception score 52%, IQR 40–72%) or radiosurgery (median speech perception score 30%, IQR 16–60%). Open-set speech perception was achieved in 61% of patients managed with microsurgery, 100% with observation, and 80% with radiosurgery. In a multivariable setting, those managed with observation (p = 0.02) or who underwent radiosurgery (p = 0.04) were significantly more likely to achieve open-set speech perception compared with patients who underwent microsurgery. Conclusions Cochlear implants offer benefit in selected patients with sporadic VS. Although achieved in over half of people after microsurgery, open-set speech perception is more reliably attained in patients who are treated with observation or radiosurgery compared with microsurgical resection. These data may inform patient counseling and VS tumor management in people who may benefit from implantation.

Abstract Background and Aims Individuals with inflammatory bowel disease (IBD) experience a high symptom burden, including abdominal pain, fatigue, anxiety, depression, and sleep disturbances; yet, little is known regarding the relationship between sex and gender on symptoms. We sought to report symptom severity for cisgender men, cisgender women, and transgender and gender-diverse (TGD) individuals. In addition, we used network analysis to identify core symptoms and explore if symptoms and their relationships differ between cisgender men and cisgender women. Methods This was a cross-sectional study. We recruited adults with IBD online through ResearchMatch. Individuals responded to Patient-Reported Outcomes Measurement Information symptom questionnaires, as well as demographic and clinical questionnaires. Network analysis was used to identify the core symptoms driving the symptom structure. Results One-hundred and fifty-seven (63.3%) participants identified as cisgender women, 84 (33.9%) as cisgender men, and 7 (2.8%) as TGD. Cisgender men (M = 61.8) and TGD (M = 61.3) groups reported higher abdominal pain levels compared with cisgender women (M = 57.8; P = .02). Transgender and gender-diverse individuals reported higher depression levels (M = 64.8) compared with cisgender men (M = 56.7) and cisgender women (M = 54.4; P = .01). Using a network analysis approach, anxiety and fatigue emerged as core symptoms for the entire sample (clinically active and inactive disease), and among only those with active clinical disease. Fatigue was a top core symptom for cisgender women; anxiety emerged as a top core symptom for cisgender men. Conclusions This study highlights that fatigue and anxiety are core symptoms among individuals with IBD and demonstrates a potential sex and/or gender difference in core symptoms. Replication of this study is needed with further consideration of inclusion of TGD patients.

Asthma is a heterogeneous chronic lung disease that affects nearly 340 million people globally. Airway hyperresponsiveness, remodeling (thickening and fibrosis), and mucus hypersecretion are some hallmarks of asthma. With several current treatments having serious side effects from long-term use and a proportion of patients with uncontrolled asthma, there is an urgent need for new therapies. With an increasing understanding of asthma pathophysiology, there is a recognized need to target therapies to specific cell types of the airway, which necessitates the identification of delivery systems that can overcome increased mucus and thickened airways. Nanoparticles (NPs) that are highly customizable (material, size, charge, and surface modification) are a potential solution for delivery systems of a wide variety of cargoes (nucleic acids, proteins, and/or small molecules), as well as sole therapeutics for asthma. However, there is a need to consider the safety of the NPs in terms of potential for inflammation, toxicity, nonspecific targets, and accumulation in organs. Ongoing clinical trials using NPs, some FDA-approved for therapeutics in other diseases, provide confidence regarding the potential safety and efficacy of NPs in asthma treatment. This review highlights the current state of the use of NPs in asthma, identifying opportunities for further improvements in NP design and utilization for targeting this chronic lung disease.

Abstract To examine the activity of ibrutinib in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after the US Food and Drug Administration approval, we conducted a multicenter retrospective study. Data were standardly collected (N = 270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), gastrointestinal (GI) (26%), lung (27%), liver (19%), genital (7%), and others (4.4%). The National Institutes of Health (NIH) severity was mild in 5.7%, moderate 42%, and severe 53%. Thirty-nine percent had overlap subtype. Karnofsky performance status (KPS) was ≥80% in 72%. The median prednisone was 0.21 mg/kg (0-2.27). Ibrutinib was started at a median of 18.2 months after cGVHD onset and in earlier lines of therapy (second line, 26%; third, 30%; fourth, 21%; fifth, 9.6%; sixth, 10%; seventh or higher, 1.2%). Among evaluable patients, the 6-month NIH overall response rate (ORR; complete response [CR]/partial response [PR]) was 45% (PR 42%; CR 3%). The median duration of response was 15 months (range, 1-46). Liver involvement had association with 6-month ORR (multivariate [MVA] odds ratio, 5.49; 95% confidence interval [CI], 2.3-14.2; P < .001). The best overall response was 56%, with most (86%) achieving by 1 to 3 months. With a median follow-up for survivors of 30.5 months, failure-free survival (FFS) was 59% (53%-65%) at 6 months and 41% (36%-48%) at 12 months. On MVA, increased age (hazard ratio [HR], 1.01; 95% CI, 1.0-1.02; P = .033), higher baseline prednisone (HR, 1.92; 95% CI, 1.09-3.38; P = .032), and lung involvement (HR, 1.58; 95% CI, 1.1-2.28; P = .016) had worse FFS. Ibrutinib discontinuation was most commonly due to progressive cGVHD (44%) or toxicity (42%). These data support that ibrutinib has activity in SR-cGVHD, provide new insight into factors associated with response and FFS, and demonstrate the toxicity profile associated with discontinuation.

Background: Delivering ethical care in global plastic surgery is challenging due to the unique complexities of resource-limited settings. Additionally, the rise of medical tourism has highlighted the importance of informed consent and awareness of the potential risks that are associated with seeking medical care in foreign countries. This article aims to consider core medical ethics principles and apply them in the context of delivering global plastic surgery. Methods: This article examines the application of the four core medical ethics principles in a framework set forth by Beauchamp and Childress, namely autonomy, beneficence, nonmaleficence, and justice, in the context of delivering plastic surgery in international settings. A literature review was performed, where all potential global plastic surgery articles were reviewed to better understand the application of the four core medical ethics framework in this context. Results: Increased communication between visiting surgeons and local healthcare providers; heightened education of surgeons traveling to low-to-middle-income countries regarding local medical practices, resource availability, and cultural norms before providing surgical education; and a greater emphasis on collecting and publishing data analyzing short- and long-term outcomes in low-to-middle-income countries are all likely to improve the success of international medical missions, ensuring that all patients receive medical treatment in a manner that upholds Beauchamp and Childress’ four core medical ethics principles. Conclusion: Providing plastic and reconstructive surgery abroad can be done ethically if the four main principles of medical ethics (respect for autonomy, beneficence, nonmaleficence, and justice) are used.

Abstract Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating toxicity of many drugs used in cancer treatment. There are numerous available strategies for preventing or treating CIPN, but few are guideline-recommended, due to limited evidence of their effectiveness. The primary objective of this survey was to understand what strategies patients used to prevent or treat CIPN, and to understand their perceptions around CIPN prevention and treatment. Methods: The Multinational Association of Supportive Care in Cancer (MASCC) Neurological Complications Study Group created a cross-sectional online survey to recruit individuals who are currently or had previously received neurotoxic chemotherapy treatment and self-reported peripheral neuropathy. Descriptive statistics were reported. Results: Most of the 447 survey participants did not use any CIPN prevention strategy (71%), though given options of any strategy the plurality preferred a prescribed medication or supplement (30%). The most common treatment strategy used was exercise (47%), with some patients trying prescription medications including non-guideline recommended gabapentin (33%) or guideline-recommended duloxetine (8%) options. Nearly half of participants (49%) used at least one non-prescribed medication for treating CIPN. Patient’s often followed suggestions of their medical oncology clinical team, but sometimes relied on the internet or other patients to recommend non-prescription strategies. Conclusion: In the absence of many guideline-recommended strategies for CIPN prevention and treatment, some patients use options with minimal evidence of effectiveness. Additional research is needed to determine which strategies are effective for prevention and treatment so these can be implemented in practice to improve treatment outcomes in patients with cancer.