Citations

Background Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), is a rare subset of primary cutaneous lymphoma known for its aggressive behavior, poor prognosis, and limited treatment options, particularly in the relapsed or refractory setting. We report a case of a patient diagnosed with PCDLBCL-LT who achieved a clinically significant response and sustained remission for seven months with acalabrutinib, a covalent inhibitor of Bruton’s tyrosine kinase (BTK), before disease progression. Case presentation An 88-year-old woman presented with a rapidly enlarging ulcerated lesion on the left lower leg. Histopathological and immunohistochemical analyses confirmed the diagnosis of PCDLBCL-LT. She was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemoimmunotherapy, followed by external beam radiation therapy (RT). These interventions resulted in only a partial response, and the disease progressed within several months. The patient was receiving direct oral anticoagulant (DOAC) therapy for left lower limb deep vein thrombosis, and she also had a history of hypertension. Considering the increased risk of major bleeding associated with DOAC use and the elevated risk of cardiovascular adverse events previously reported with ibrutinib, an alternative BTK inhibitor was considered. Accordingly, she was initiated on acalabrutinib at a dose of 100 mg orally twice daily. The patient exhibited a rapid and robust clinical response, with complete resolution of cutaneous lesions and sustained remission lasting seven months. Ultimately, the disease progressed, and given her advanced age and overall poor performance status, she was transitioned to hospice care. She subsequently died 14 months after initiating acalabrutinib. Conclusion This report documents the first known case of successful treatment of relapsed/refractory PCDLBCL-LT with acalabrutinib. Despite advanced age and poor performance status, the patient experienced rapid symptom resolution and durable remission without treatment-related adverse events. These findings suggest that BTK inhibitors may represent a promising therapeutic approach for PCDLBCL-LT, either as monotherapy or in combination with anti-CD20 antibodies. Further investigation into novel targeted therapies is urgently needed for this rare and aggressive lymphoma subtype.

ABSTRACT Introduction Urinary tract infections (UTIs) are the most common infectious complication in kidney transplant (KT) recipients. UTI risk is associated with frailty in older adults, and UTIs may exacerbate frailty. However, this relationship has not been described in KT recipients who are at both greater risk of frailty and UTIs. Methods We conducted a retrospective chart review of 90 KT recipients aged ≥ 50 years who underwent KT between January and July 2021 and had ≥ 12 months of post‐transplant follow‐up. UTIs were identified at the time of each occurrence. Frailty was assessed at baseline using the modified Rockwood‐20 frailty index (mFI); scores ≥ 0.25 were considered frail, 0.08–0.24 pre‐frail, and < 0.08 non‐frail. The primary outcome was cumulative UTI occurrence based on frailty status, analyzed using Cox proportional hazards regression. Results Among 90 KT recipients, 33 (37%) developed ≥ 1 UTI. Notably, 45% of KT recipients with UTIs were frail, compared to 25% of KT recipients without UTIs. Compared to non‐frail KT recipients, frail KT recipients had a significantly higher risk of UTIs (HR 8.13, 95% CI 1.89, 34.91; p = 0.005), as did pre‐frail KT recipients (HR 4.51, 95% CI 1.02, 19.92; p = 0.047). Frail KT recipients also experienced earlier UTI onset, with 12 out of 21 total UTIs (57%) occurring within the first 30 days post‐KT. Conclusion Frailty and prefrailty are associated with increased UTI risk in KT recipients. These findings highlight the importance of frailty assessment in post‐transplant care and suggest the need for targeted interventions to reduce UTI risk in this vulnerable population. image

Abstract Purpose Clinicians and scientists often take a different path in developing competence and confidence as educators compared with peers who have received formal pedagogical teaching. This study explores how award-winning health professions educators reflect on the development and fluctuation of their teaching self-efficacy over time. Guided by social cognitive theory, the study investigates how educators notice, make meaning of, and respond to diverse teaching-related experiences across their careers. Method Between May and August 2023, 31 Mayo Clinic educators in clinical medicine, basic science, and allied health who had been recognized for teaching excellence in the past 10 years were invited to participate in semistructured interviews. Each participant first completed a preinterview survey and created a graph of their teaching confidence over time, which served as an anchor for the interview discussion. Reflexive thematic analysis identified patterns in how participants described sources of fluctuation in teaching self-efficacy. Results Of the 31 invited educators, 21 (11 women, 10 men) took part in an interview. Educators described varied trajectories of teaching self-efficacy over time shaped by different experiences, interpretations, and instructional experimentation. Four themes were identified: (1) interpreting implicit and explicit feedback, (2) revising beliefs in response to successes and setbacks, (3) adapting to changing contexts, and (4) using social models to gauge effectiveness. Participants reported becoming more responsive to situational demands and learner needs over time. Conclusions For these award-winning educators, teaching self-efficacy was constructed and reconstructed through an adaptive, socially situated process of interpretation and reflection. The same events may have affected self-efficacy differently, depending on how individuals framed and acted on their experiences. Findings support a model that emphasizes adaptive expertise and offers implications for faculty development.

ABSTRACT Background Patients with gastroparesis (Gp) can have a variety of symptoms. Apart from use of prokinetics, symptomatic therapies for the predominant symptom (PrS) are used. Aims (1) To classify Gp patients based on their PrS; (2) To determine differences in Gp symptoms, gastric emptying (GE), quality of life (QOL), treatments, and symptom improvement among Gp patients with different PrS. Methods Gp patients were enrolled in a multicenter registry and followed for 96‐weeks. Patients recorded their PrS and completed questionnaires assessing symptoms and QOL at enrollment and at follow up visits. Results Of 1013 Gp patients (361 diabetic, 607 idiopathic, 45 post‐fundoplication), the PrS were nausea (31%), vomiting (20%), abdominal pain (20%), bloating (9%), fullness (4%), GERD (4%), constipation (3%). Abdominal pain was more often a PrS in idiopathics, whereas vomiting was more often a PrS in diabetics. QOL scores were lower in the abdominal pain PrS group. PrS was associated with greater use of directed symptomatic treatment (antiemetic agents and gastric electrical stimulation for nausea and vomiting, prokinetic agents for vomiting and fullness, and constipation medications for constipation). Of 555 patients followed over 48 weeks, GCSI improved by ≥ 1 in 26% overall, more often in patients with initial PrS of nausea (32%) and bloating (35%) and less often for initial PrS of fullness (13%) or abdominal pain (15%). Conclusions In Gp patients, the most common PrS were nausea, vomiting, and abdominal pain. PrS is associated with QOL, treatments utilized, and patient outcomes. Thus, the PrS of a patient with Gp provides useful information about their present condition and future outcome.

Community organisations, alternative schools and business institutions worldwide prepare youth for the workforce. Since the COVID-19 pandemic, changes in work—life decisions and business needs have led to a shortage of talent. To equip students with the skills and mindset needed to be future ready, the power of diversity, equity and inclusion (DEI) must be harnessed through a network of meaningful connections and partnerships. A small group at Mayo Clinic, sharing a common interest in DEI and the local community, explored ways to encourage diverse, young talent to embark on careers in science, technology, education and mathematics. Input from community organisations and professionals indicated that collaborating with educational institutions is vital, which led to the initiation of a pilot programme involving one high school. The group collaborated with the school’s Work Experience Coordinator and students to develop and implement a pilot Career Preparation Programme (CPP) as part of a Work Experience Seminar (WES) course to deepen students’ knowledge of healthcare careers and provide one-on-one and group mentorship. Through discussions about career possibilities, levers of success and a higher purpose, the team sought to help students appreciate available and attainable career opportunities. Student evaluations were conducted after each of the two semesters. A total of 93 students participated in the pilot programme, of whom 85 (91 per cent) reported that the combined offering was engaging and worthwhile. The primary takeaways were ‘the importance of soft skills’, ‘following dreams and passions’ and ‘being a lifelong learner’. Inspired by this experience, the students established a club focused on career mentoring and tutoring. Throughout the process, trust, credibility and role modelling were emphasised. In addition, flexibility, patience and openness to bidirectional learning and creative ideas were identified as the main elements of programme’s success. The team plans to expand the pilot programme to include a non-healthcare focus and implement the programme at additional high schools. This article is also included in The Business & Management Collection which can be accessed at https://hstalks.com/ business/.

Abstract Background Genetic testing is increasingly used in presurgical evaluation, but the yield of resection across germline genetic epilepsies remains uncertain. Methods We conducted a systematic review of MEDLINE (PubMed) and Scopus and added cases from three institutional cohorts and the Pediatric Epilepsy Research Consortium (PERC) databases, including individuals with pathogenic/likely pathogenic germline variants besides tuberous sclerosis and neurofibromatosis who underwent resection or laser ablation. Etiologies were grouped into biologically informed categories (GATORopathies, vascular, overgrowth, CNVs, channelopathies, synaptopathies, other). Primary outcome was seizure freedom (Engel I) at last follow-up. Group comparisons used Fisher’s exact and Kruskal–Wallis tests (α=0.05; Bonferroni when applicable). Prespecified sensitivity analyses stratified by lesional status, excluded GATORopathies, and restricted to literature-only cases. Results We included 223 literature cases (64 studies), 35 institutional cases, and 11 PERC cases (n=269). Median follow-up was 24 months (IQR 12–48.0). Seizure freedom was achieved in: vascular disorders 14/19 (73.6%), GATORopathies 79/120 (67.5%), CNVs 18/31 (66.7%), overgrowth 7/13 (53.8%), other 16/25 (41.7%), channelopathies 13/43 (33.3%), and synaptopathies 4/18 (22.2%) (overall p<0.001). Among cases with known imaging, 208/253 (82.2%) had epileptogenic MRI lesions, including 64% of channelopathies and 80% of the synaptopathies. In univariate contrasts (each category vs all others), odds of seizure freedom were higher for vascular disorders (2.66-fold, 95% CI 0.87–9.72) and GATORopathies (2.46-fold, 95% CI 1.46–4.18), and lower for synaptopathies (∼4.2-fold lower, OR 0.24, 95% CI 0.05– 0.78) and channelopathies (∼4.5-fold lower, OR 0.22, 95% CI 0.09–0.48). Direction and magnitude were consistent across prespecified sensitivity analyses (lesional-only, literature-only, exclusion of GATORopathies). Conclusions Resective surgeries can be effective in germline genetic epilepsies, but outcomes vary by pathway. Disorders with discrete, lesional substrates (GATORopathies, vascular) show the highest likelihood of seizure freedom, whereas channelopathies and synaptopathies, despite the presence of MRI lesions, have substantially lower yields even in lesional cases. Prospective, genotype-aware surgical registries with standardized reporting (EEG, imaging, pathology) and time-to-event outcomes are needed to refine the selection of surgical candidates and quantify seizure and non-seizure-related outcomes.

ABSTRACT Cellular senescence in the kidney plays a crucial role in the progression of acute kidney injury and chronic kidney disease. Therapeutic approaches targeting senescent cells, such as small molecule senolytic and senomorphic drugs, display efficacy in preclinical models. However, such drugs pose a risk of adverse effects and only partially mitigate disease progression, highlighting the need for new therapeutic approaches that more comprehensively and safely address disease pathways in aging kidney disease. This review discusses the potential of extracellular vesicles and longevity proteins, such as α‐klotho and silencing information regulator 2‐related enzyme 1 (SIRT1), in regulating cellular senescence and alleviating kidney fibrosis. Particularly, combination therapy that simultaneously targets inflammation, tissue damage, and senescence is promising for kidney disease, given the potential to synergistically overcome the limitations of current unimodular treatment modalities and pave the way for more effective management of kidney disease. This review highlights the mechanisms of cellular senescence in kidney disease, particularly in diabetic kidney disease, the latest knowledge on senotherapy, and the potential and challenges of new therapeutic strategies, including combining extracellular vesicles and longevity proteins.

ABSTRACT Background Chemotherapy‐induced peripheral neuropathy (CIPN), characterized by loss of sensation and impaired physical function, is a prevalent and debilitating side effect of chemotherapy, affecting 30%–50% of breast cancer survivors (BCS) with effects lasting years after treatment completion. Mindfulness‐based interventions are shown to be efficacious in reducing symptoms in neuropathies. This subgroup analysis examined the effect of Mindfulness‐Based Stress Reduction on Breast Cancer (MBSR(BC)) compared to Breast Cancer Education Support (BCES) or Usual Care (UC) on CIPN among BCS who received chemotherapy or chemotherapy and radiation. Methods BCS ( n = 114) were randomly assigned to the 6‐week MBSR(BC) ( n = 48), BCES ( n = 52), or UC ( n = 14) regimen. Demographic and clinical data were assessed at baseline, and CIPN was assessed using the Chemotherapy‐Induced Peripheral Neuropathy assessment tool (CIPNAT) at baseline, 6, 12, and 26 weeks. Between‐ and within‐group differences were evaluated and change over time was compared between groups. Results BCS (mean age = 52.7 years, range: 28–81 years) were primarily White and non‐Hispanic ( n = 78, 68%). The pattern of effect sizes was similar for CIPNAT symptoms and interference with improvements in CIPN for MBSR(BC) and BCES groups overtime. For both groups, the effects were larger compared to the UC. Differences tended to increase over time with significant effects observed between MBSR(BC) and UC, and between BCES and UC at weeks 12 and 26. Conclusions The findings indicate that MBSR(BC) and BCES may effectively reduce CIPN symptoms among BCS compared to UC. MBSR(BC) and BCES programs are effective non‐pharmacological interventions for CIPN that may translate into practice.

Abstract Context Data on cognition in patients with primary aldosteronism (PA) are scarce. Mild autonomous cortisol secretion (MACS), defined based on post-dexamethasone cortisol &gt;1.8 mcg/dL, is diagnosed in up to 30% of patients with PA. Objectives (1) Assess cognition in patients with PA vs referent subjects with hypertension and (2) determine differences in cognition between patients with PA and those with MACS. Methods A prospective, cross-sectional study, 2019-2023. Cognition was assessed by National Institute of Health Toolbox Cognition Battery and reported as T-scores corrected for age, sex, race, and education. Only subjects with hypertension were included. Results Cognitive assessment was performed in 52 patients with PA (including 11 patients with both PA and MACS, median age of 51.0 years, 30 (57.7%) women), 47 patients with MACS (median age of 57.0 years, 31 (66.0%) women), and 52 referent subjects (median age of 66.1 years, 30 (57.7%) women). When compared to referents, and after adjusting for age, smoking, systolic blood pressure, and alcohol use, patients with PA had lower total cognition (β = −5.7, P = .023), notably fluid cognition (β = −6.8, P = .017), including attention and executive function (β = −5.6, P = .012) and cognitive flexibility and executive function (β = −8.2, P = .006). When compared to patients with MACS, patients with PA had a higher processing speed (β = 9.0, P = .003). No differences in cognition were found between patients with PA with and without MACS. Conclusion Patients with PA demonstrated lower cognition compared with referents and processing speed compared with MACS. Future studies should characterize the impact of MACS on the cognition of patients with PA.