Natural history of visceral branch artery dissections and the influence of concurrent aortic dissection on overall and intervention-free survival.

OBJECTIVE: Visceral branch artery dissection (VBAD) is uncommon and may occur with or without an associated aortic dissection (AD). We hypothesized that isolated VBAD would have a more benign clinical course than those with concurrent AD and compared survival outcomes stratified based on aortic involvement. METHODS: VBAD over a 5-year period were identified using International Classification of Diseases codes. Data related to patient demographics, comorbid conditions, clinical presentation, management (including procedural interventions), and survival were obtained from medical records. Anatomic imaging studies were reviewed to characterize anatomy, including the presence or absence of concurrent AD. Overall survival and intervention-free survival were evaluated using Kaplan-Meier and Cox proportional hazards models. RESULTS: A total of 299 VBAD were identified, 174 of which were isolated VBAD and 125 were associated with concurrent AD. Seventy-one percent of patients were men, 77% were White, and 85% were non-Hispanic. The mean age was 61.1 ± 14.4 years. The mean follow-up was 53.2 ± 50.0 months. The estimated overall survival was 88.2% and the estimated overall intervention-free survival was 55.6% at 12 months. Isolated VBAD had better overall survival than those with concurrent AD (69.2% vs 32.4%; P < .001). Concurrent AD was also associated with inferior intervention-free survival (57.5% vs 7.3%; P < .001). Acute presentation was associated with decreased intervention-free survival (86.1% vs 13.4%; P < .001). Acute presentation was also associated with decreased overall survival in patients with isolated VBAD (60.8% vs 80.0% at 180 months; P < .001) and inferior intervention-free survival (48.4% vs 69.5% at 180 months; P < .001) in the subgroup of patients with isolated VBAD. Multivariable Cox models identified that age (hazard ratio [HR]: 1.05, standard deviation [SD]: 0.02; P = .001) was associated with inferior survival and renal dissections (HR: 3.08, SD: 0.99; P = .001) or mesenteric and renal dissections (HR: 3.39, SD: 1.44; P = .004) were associated with inferior intervention-free survival. CONCLUSIONS: Isolated VBAD has superior overall and intervention-free survival to those associated with concurrent AD. The absence vs presence of aortic involvement is useful for risk stratification and may support tailored approaches to the frequency of imaging surveillance.

Synthetic biology approaches for enhancing safety and specificity of CAR-T cell therapies for solid cancers.

CAR-T cell therapies have been successful in treating numerous hematologic malignancies as the T cell can be engineered to target a specific antigen associated with the disease. However, translating CAR-T cell therapies for solid cancers is proving more challenging due to the lack of truly tumor-associated antigens and the high risk of off-target toxicities. To combat this, numerous synthetic biology mechanisms are being incorporated to create safer and more specific CAR-T cells that can be spatiotemporally controlled with increased precision. Here, we seek to summarize and analyze the advancements for CAR-T cell therapies with respect to clinical implementation, from the perspective of synthetic biology and immunology. This review should serve as a resource for further investigation and growth within the field of personalized cellular therapies.

Biomaterial-enhanced treg cell immunotherapy: A promising approach for transplant medicine and autoimmune disease treatment.

Regulatory T cells (Tregs) are crucial for preserving tolerance in the body, rendering Treg immunotherapy a promising treatment option for both organ transplants and autoimmune diseases. Presently, organ transplant recipients must undergo lifelong immunosuppression to prevent allograft rejection, while autoimmune disorders lack definitive cures. In the last years, there has been notable advancement in comprehending the biology of both antigen-specific and polyclonal Tregs. Clinical trials involving Tregs have demonstrated their safety and effectiveness. To maximize the efficacy of Treg immunotherapy, it is essential for these cells to migrate to specific target tissues, maintain stability within local organs, bolster their suppressive capabilities, and ensure their intended function's longevity. In pursuit of these goals, the utilization of biomaterials emerges as an attractive supportive strategy for Treg immunotherapy in addressing these challenges. As a result, the prospect of employing biomaterial-enhanced Treg immunotherapy holds tremendous promise as a treatment option for organ transplant recipients and individuals grappling with autoimmune diseases in the near future. This paper introduces strategies based on biomaterial-assisted Treg immunotherapy to enhance transplant medicine and autoimmune treatments.

Claustrum projections to the anterior cingulate modulate nociceptive and pain-associated behavior.

The anterior cingulate cortex (ACC) is critical for the perception and unpleasantness of pain.1,2,3,4,5,6 It receives nociceptive information from regions such as the thalamus and amygdala and projects to several cortical and subcortical regions of the pain neuromatrix.7,8 ACC hyperexcitability is one of many functional changes associated with chronic pain, and experimental activation of ACC pyramidal cells produces hypersensitivity to innocuous stimuli (i.e., allodynia).9,10,11,12,13,14 A less-well-studied projection to the ACC arises from a small forebrain region, the claustrum.15,16,17,18,19,20 Stimulation of excitatory claustrum projection neurons preferentially activates GABAergic interneurons, generating feed-forward inhibition onto excitatory cortical networks.21,22,23,24 Previous work has shown that claustrocingulate projections display altered activity in prolonged pain25,26,27; however, it remains unclear whether and how the claustrum participates in nociceptive processing and high-order pain behaviors. Inhibition of ACC activity reverses mechanical allodynia in animal models of persistent and neuropathic pain,1,9,28 suggesting claustrum inputs may function to attenuate pain processing. In this study, we sought to define claustrum function in acute and chronic pain. We found enhanced claustrum activity after a painful stimulus that was attenuated in chronic inflammatory pain. Selective inhibition of claustrocingulate projection neurons enhanced acute nociception but blocked pain learning. Inversely, chemogenetic activation of claustrocingulate neurons had no effect on basal nociception but rescued inflammation-induced mechanical allodynia. Together, these results suggest that claustrocingulate neurons are a critical component of the pain neuromatrix, and dysregulation of this connection may contribute to chronic pain.

Nasopharyngeal cancer mortality in disaggregated Asian and non-Asian Americans.

BACKGROUND: Nasopharyngeal carcinoma (NPC) mortality varies based on multiple risk factors. While NPC mortality is higher in Asia, little is known about Asian subgroups in the United States (US). METHODS: Using the 2005-2020 National Vital Statistics System, we examined NPC mortality by age, race (non-Hispanic black, Hispanic white (HW), non-Hispanic white (NHW), Chinese, Filipino, Asian Indian, Japanese, Korean, Vietnamese), sex, and nativity (Untied States or foreign-born). RESULTS: Upon disaggregation, Chinese (1.96 [CI: 1.78-2.16]), Filipino (0.68 [0.68-1.11]), and Vietnamese Americans (0.68 [0.52-1.10]) had the top age-adjusted mortality rates (AAMR per 100 000 person-years). Foreign-born Chinese, Vietnamese, Filipinos, Asian Indians, and NHW had higher AAMRs compared to US-born persons. All male groups had higher AAMR compared to females. Stratifying for race, nativity, and sex, foreign-born Chinese males (4.09 [3.79-4.40]) had the highest AAMR. CONCLUSION: These findings demonstrate the importance of disaggregating NPC mortality data by Asian subgroups, providing valuable insights for targeted public health interventions in the United States.

Leading causes of death in Vietnamese Americans: An ecological study based on national death records from 2005-2020.

BACKGROUND: Disaggregated data is a cornerstone of precision health. Vietnamese Americans (VietAms) are the fourth-largest Asian subgroup in the United States (US), and demonstrate a unique burden of disease and mortality. However, most prior studies have aggregated VietAms under the broader Asian American category for analytic purposes. This study examined the leading causes of death among VietAms compared to aggregated Asian Americans and non-Hispanic Whites (NHWs) during the period 2005-2020. METHODS: Decedent data, including underlying cause of death, were obtained from the National Center for Health Statistics national mortality file from 2005 to 2020. Population denominator estimates were obtained from the American Community Survey one-year population estimates. Outcome measures included proportional mortality, age-adjusted mortality rates per 100,000 (AMR), and annual percent change (APC) in mortality over time. Data were stratified by sex and nativity status. Due to large differences in age structure, we report native- and foreign-born VietAms separately. FINDINGS: We identified 74,524 VietAm decedents over the study period (71,305 foreign-born, 3,219 native-born). Among foreign-born VietAms, the three leading causes of death were cancer (26.6%), heart disease (18.0%), and cerebrovascular disease (9.0%). Among native-born VietAms the three leading causes were accidents (19.0%), self-harm (12.0%), and cancer (10.4%). For every leading cause of death, VietAms exhibited lower mortality compared to both aggregated Asians and NHWs. Over the course of the study period, VietAms witnessed an increase in mortality in every leading cause. This effect was mostly driven by foreign-born, male VietAms. CONCLUSIONS AND RELEVANCE: While VietAms have lower overall mortality from leading causes of death compared to aggregated Asians and NHWs, these advantages have eroded markedly between 2005 and 2020. These data emphasize the importance of racial disaggregation in the reporting of public health measures.

The Inequitable Experiences of Left-Handed Medical Students in Surgical Education.

PURPOSE: Left-handed medical students contend with unique educational barriers within surgery, such as lack of educational resources, lack of left-handed-specific training, and widespread stigmatization of surgical left-handedness. This study aimed to highlight the surgical experiences of left-handed medical students so educators may be empowered to act with greater care and appreciation of these students' circumstances. METHOD: In this qualitative study, the authors conducted semistructured interviews on surgical experiences during medical school between January 31, 2021, and June 20, 2021, on 31 current surgical residents and fellows from 15 U.S. institutions and 6 surgical specialties. Left-handed trainees were included regardless of their surgical hand dominance. RESULTS: The authors identified 3 themes related to left-handed medical students' surgical experience: (1) disorienting advice from faculty or residents, (2) discouraging right-handed pressures and left-handed stigmatization, and (3) educational wishes of left-handed medical students. Trainees describe dialogues during medical school in which their handedness was directly addressed by residents and faculty with disorienting and nonbeneficial advice. Often trainees were explicitly told which hand to use, neglecting any preferences of the left-handed student. Participants also described possible changes in future surgical clerkships, including normalization of left-handedness, tangible mentorship, or granular and meaningful instruction. CONCLUSIONS: Left-handed medical students encounter unique challenges during their surgical education. These students report being disoriented by the variability of advice provided by mentors, discouraged by how pressured they feel to operate right-handed, and burdened by the need to figure things out by themselves in the absence of adequate left-handed educational resources. Surgical education leadership should detail the unique problems left-handed learners face, impartially elicit the learner's current operative hand preference, take responsibility for their left-handed students, promote acceptance and accommodation strategies of left-handed surgical trainees, and endeavor to improve the breadth of left-handed surgical resources.

Community and Healthcare Perspectives on Implementing Hypertension Interventions for a Multiethnic Safety-Net Population.

Objective: To synthesize community and healthcare informants' perspectives on contextual considerations and tailoring recommendations for high-quality, sustainable implementation of evidence-based practices (EBPs) for managing hypertension (HTN) in a multiethnic safety-net population. Design: Structured focus-group discussions and semistructured qualitative interviews. Background: High-quality, sustainable implementation of HTN-related EBPs can promote equitable care. Implementation challenges extend beyond individual patients to span multiple levels of context. Few studies have systematically engaged community and healthcare perspectives to inform the design of HTN intervention trials. Setting: A large safety-net healthcare system. Participants/Methods: We conducted four structured discussions with each of five race- or ethnicity-specific community action boards (CABs) to understand community members' HTN-related norms, assets, needs, and experiences across local healthcare systems. We interviewed 41 personnel with diverse roles in our partnered healthcare system to understand the system's HTN-related strengths and needs. We solicited EBP tailoring recommendations from both groups. We summarized the findings using rapid content analysis. Results: Participants identified contextual considerations spanning seven themes: social determinants, healthcare engagement, clinical interaction, system operations, standardization, patient education, and partnerships and funding. They offered tailoring recommendations spanning nine themes: addressing complex contexts, addressing social needs, system operations, healthcare system training and resources, linguistic and cultural tailoring, behavioral engagement, relational engagement, illness-course engagement, and community partnerships. Conclusions: Engaging community and healthcare informants can ground implementation in the policy, community, healthcare system, clinical, and interpersonal contexts surrounding diverse patients at risk for disparities. Such grounding can reframe inequitable implementation as a multilevel social problem facing communities and healthcare systems, rather than individuals.