Clonal hematopoiesis, particularly clonal hematopoiesis of indeterminate potential and clonal cytopenia of undetermined significance, is an age-related premalignant condition characterized by the expansion of hematopoietic clones carrying somatic mutations. Because of the accessibility of peripheral blood, it has been increasingly detected, even in otherwise healthy individuals. Although often asymptomatic, specific clonal hematopoiesis-associated mutations and clonal features are associated with an increased risk of progression to hematologic malignancies, including myelodysplastic syndromes and acute myeloid leukemia. Beyond malignant transformation, clonal hematopoiesis also has systemic implications and has been linked to a variety of nonmalignant conditions, such as cardiovascular and inflammatory disease. In this review, we focus on the clinical management of clonal hematopoiesis, including approaches to diagnosis, tools for risk stratification, and strategies for surveillance and comorbidity mitigation. In the absence of consensus guidelines and approved therapies, management remains individualized, underscoring the need for continued research and clinical trials to guide evidence-based care and improve patient outcomes.

The year 2025 marked significant advances in autologous cellular therapy for melanoma and solid tumors, building on landmark regulatory approvals in 2024. Lifileucel, the first Food and Drug Administration-approved tumor-infiltrating lymphocyte (TIL) therapy for advanced melanoma, demonstrated durable efficacy in the 5-year analysis of the C-144-01 trial, with an objective response rate (ORR) of 31.4% and prolonged responses in a heavily pretreated population. Real world data further supported its effectiveness, with higher ORR likely reflecting earlier lines of therapy and differences in patient selection. Preferentially expressed antigen in melanoma (PRAME)-targeted T-cell receptor (TCR) T-cell therapy (anzu-cel, IMA203) showed promising activity in a phase 1 study, with ORR of approximately 50% in checkpoint inhibitor refractory melanoma, durable responses, and manageable toxicity, validating PRAME as a high value target across multiple tumor types. Next-generation engineered TIL approaches emerged to address limitations of high-dose IL-2. OBX-115, an IL-2 independent TIL platform expressing membrane-bound IL-15 regulated by acetazolamide, demonstrated early clinical activity with ORR of 67% in initial phase 1 data. Additional strategies, including CRISPR-mediated gene editing and checkpoint disruption, highlight a shift toward programmable, self-sustaining cellular therapies. Personalized neoantigen-based therapies advanced with early clinical validation of adoptive T-cell platforms and mRNA vaccines, demonstrating immune activation and improved recurrence-free survival in melanoma. Finally, afamitresgene autoleucel (afami-cel), a MAGE-A4 directed TCR-T therapy, showed durable efficacy in synovial sarcoma and expanding activity across solid tumors, establishing proof of concept for TCR-T approaches. Collectively, these advances position autologous cellular therapy as an evolving standard of care in melanoma and a promising modality across solid tumors, with ongoing efforts focused on improving accessibility, overcoming resistance, and optimizing combinatorial strategies.

Cuproptosis, a copper-dependent form of regulated cell death, represents a potential therapeutic vulnerability in colorectal cancer (CRC). However, the regulatory mechanisms governing cuproptosis in CRC remain largely unknown.

UBE2D4 expression was analyzed in the TCGA-COAD cohort and validated in CRC cell lines (HCT116, HT29) and normal colon epithelial cells (FHC) by qRT-PCR and western blot. Paired CRC and adjacent normal tissues (n = 5) were also examined by western blot. UBE2D4-knockdown HT29 cells were generated by transient siRNA transfection to assess cell viability (CCK-8), migration (wound healing assay), and expression of cuproptosis-related genes (DLAT, HSP70, LIAS) under copper overload conditions (elesclomol+CuSO₄).

UBE2D4 was significantly upregulated in CRC tissues and cell lines compared to normal controls. In paired clinical samples, western blot confirmed that UBE2D4 protein expression was elevated in tumor tissues, accompanied by increased DLAT, HSP70 and LIAS. Copper overload induced typical cuproptotic mitochondrial morphology and triggered a marked upregulation of UBE2D4, DLAT, and HSP70, alongside downregulation of LIAS. UBE2D4 silencing had no effect on baseline cell viability or migration but significantly rescued cells from copper-induced cytotoxicity. Genetically, UBE2D4 knockdown specifically attenuated the copper-induced elevation of DLAT, while restoring HSP70 and LIAS to near-baseline levels.

These findings identify UBE2D4 as a genetically upregulated and functionally significant gene in colorectal cancer. Its upregulation correlates with altered expression of cuproptosis-related genes, particularly DLAT, suggesting that UBE2D4 expression status may represent a genetic determinant of cuproptosis sensitivity in CRC. This study provides a genetic basis for stratifying CRC patients who might benefit from copper-based therapeutic strategies.

The Buschke-Löwenstein tumor (BLT), also designated giant condyloma acuminatum, represents a rare anogenital neoplasm of intermediate biological behavior, occupying a nosological boundary between benign condylomatous disease and invasive squamous cell carcinoma (SCC). Its malignant transformation potential, estimated between 30% and 56%, renders early diagnosis and accurate locoregional staging of paramount clinical importance. We report the case of a 54-year-old immunocompetent male who presented with a 2-year history of a progressively enlarging scrotal mass, ultimately measuring 12 cm at clinical assessment. Physical examination disclosed a large exophytic cauliflower-shaped lesion with surface ulceration, malodorous discharge, and bilateral inguinal lymphadenopathy. Pelvic MRI revealed a heterogeneous scrotal mass with posterior extension into the ipsilateral intergluteal fold and perineal soft tissues. Post-contrast T1-weighted sequences demonstrated avid heterogeneous enhancement. Diffusion-weighted imaging yielded a markedly reduced mean apparent diffusion coefficient value of 0.9 × 10⁻³ mm²/s within the inguinal lymph nodes, a finding supportive of, though not independently diagnostic of, nodal metastatic involvement, which was subsequently confirmed by fine-needle aspiration cytology. Histopathological examination of the surgical specimen identified a dual pattern comprising benign condylomatous areas alongside foci of invasive moderately differentiated SCC, confirming malignant transformation. This case underscores the oncological risk inherent to long-neglected anogenital condylomatous lesions and highlights the pivotal contribution of pelvic MRI-particularly diffusion-weighted sequences with ADC quantification-in delineating locoregional tumor extent, raising suspicion for nodal metastatic involvement, and guiding surgical planning in the management of Buschke-Löwenstein tumor.

Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare central nervous system neoplasms characterized by the absence of a primary brain or spinal cord tumor. Patients exhibit common radiological and histopathological features; however, the clinical progression varies. We present the case of a 4-year-old girl initially diagnosed with constipation and failure to thrive, who subsequently developed neurological signs during hospitalization. Subsequently, she was referred with suspected tuberculosis meningitis, despite negative cerebrospinal fluid (CSF) culture results, and the patient presumably started on anti-TB and methylprednisolone. Later, magnetic resonance imaging (MRI) demonstrated diffuse nodular meningeal enhancement, suggestive of infectious, autoimmune, or neoplastic etiologies. Further histopathological examination confirmed DLGNT by identifying atypical glial cells, lymphohistiocytic infiltrate, fibrosis, and the presence of the BRAF V600E mutation. Given the rarity of the condition and its recent recognition in the World Health Organization (WHO) classification, many clinicians may be unfamiliar with DLGNT. Consequently, molecular diagnosis is essential, as exemplified in this case.

After the beginning of the COVID-19 pandemic, there was a 53% increase in overdose deaths in the U.S., with the highest rates among American Indian/Alaska Natives (AI/AN) individuals compared with all racial/ethnic groups in the U.S. Historical trauma has been linked to substance use among AI/AN individuals. First cited in the 1990s, historical trauma is an intergenerational response to the loss of AI/AN communities' land, peoples, and culture secondary to colonization in North America. Two-Eyed Seeing is the gift of multiple perspectives treasured by many Indigenous peoples, which includes storytelling. The purpose of this study was to hear from the tribal members their concerns related to substance use among youth and their ideas related to prevention and treatment.

The study design was a focus group methodology. Five focus groups were completed with 20 AI/AN self-identified adults over 18 years of age.

Several themes emerged that focused on both prevention and treatment of substance use disorder. Participants expressed concern about their invisibility in state and federal datasets, lack of access to health care, and a lack of prosocial opportunities for youth to inspire their future aspirations. They expressed concern about stigma and the potential negative influences of peers and social media. Two approaches many participants felt could help were to start prevention projects early with elementary-aged youth and to take an intergenerational approach.

To more broadly understand the needs of the AI/AN medication for opioid use disorder clients, future investigations should include interviews with substance use disorder clients and their families. Further understanding of the experiences of individuals with substance use disorder and their treatment could advance creative treatment plans that are trauma-informed and culturally sensitive. Implementing community participatory action increases the assurance that the needs of AI/AN families are addressed.

The clinical impact of pharmacists and pharmacy technicians on the care of people with cystic fibrosis (pwCF) has been well documented within the literature, including medication access, reduction of hospitalizations, and consolidation of pharmaceutical delivery for pwCF with complex medication regimens. However, challenges related to access and affordability have become increasingly complex, increasing the administrative burden placed upon these members of the multidisciplinary CF care team. The goal of this study was to quantify the time pharmacists and pharmacy technicians at CF Foundation-accredited care centers (CFACC) spent triaging and resolving errors, categorize the types of interventions required, and tabulate the financial burden for pwCF averted through these interventions.

This study was a retrospective review of pharmacy team members' interactions following a change in limited distribution network of cystic fibrosis transmembrane conductance regulator modulators (CFTRm) over a 4-month period of time. Each site received institutional review board exemption. Measures were characterized using descriptive statistics and were analyzed in SAS v9.4 (Cary, NC). Collected data were extrapolated to be nationally representative based on the 2023 CFF Patient Registry report.

Six CFACC and 1781 pwCF were included in this review. Of these pwCF, 216 required additional interventions following a required change in the dispensing pharmacy for their CFTRm. Collectively, 201.5 h were spent on resolution of issues during the study period with interventions successfully averting a financial burden to pwCF of $226,094.73. Extrapolations of time and financial burden were estimated to be 3700 h and over $4.2 million, respectively.

Medication access and affordability continue to present significant barriers for pwCF. We aim to highlight the critical services provided by clinical pharmacy teams at CFACC as well as their integrated health-system specialty pharmacies, and the vital role they play in improving outcomes and providing cost-effective care for pwCF.

Effective COPD management depends on structured symptom and risk assessment, individualized therapy, and action plan provision, yet these are inconsistently delivered in routine care. Electronic health record (EHR)-integrated clinical decision support systems (CDSSs) can help close these gaps but require accurate, structured patient data to drive their recommendations. Digital pre-visit questionnaires are increasingly used to collect such data, but patient preferences for their content and design remain poorly understood, particularly in COPD.

We used a user-centered design process to develop an electronic COPD questionnaire to inform an EHR-integrated CDSS. Content was mapped to planned CDSS actions and built into a mobile-optimized prototype using eHealth design principles. We face validated the prototype with 10 people living with COPD, then refined it through successive focus groups until saturation. Usability was assessed with the System Usability Scale (SUS) and Likert ratings and transcripts were analyzed thematically.

Face validation (n=10) and three focus groups (n=13) were conducted to saturation. Four critical issues were identified and addressed. Usability was high throughout (mean SUS 88.07, "excellent"), with strong Likert ratings for functionality, navigation, and appearance. Thematic analysis yielded four themes: standardized measures versus real-life experience; usability and format as enablers; support for communication, memory, and efficient care; and desire for transparency and education.

Through iterative co-design with older adults, we developed an EHR-integrated electronic COPD questionnaire with excellent usability and relevance to patients' lived experience. Patients anticipated benefits beyond data capture: improved symptom recall, visit preparation, and provider efficiency. This is one of the first electronic COPD questionnaires developed through structured patient co-design and qualitative evaluation, providing a transferable model for tools that inform clinical decision support.

Chronic obstructive pulmonary disease (COPD) is frequently complicated by nutritional disorders, and low body weight is an independent prognostic factor. High-intensity exercise training may affect leptin, an appetite-regulating hormone, and dietary intake. However, longitudinal evidence regarding these associations in COPD is limited. This study aimed to examine changes in dietary intake and leptin levels during pulmonary rehabilitation in patients with COPD, with exploratory analyses according to attainment of high-intensity exercise training.

In this prospective observational study, patients with COPD participated in a 6-week pulmonary rehabilitation program. High-intensity exercise training (≥ 80% prescribed intensity) was performed whenever feasible. Dietary intake (primary outcome) and leptin were assessed before and after the program. In exploratory subgroup analyses, participants were classified as high-intensity "attainers" (Attainment group) or "nonattainers" (Nonattainment group), and within-group before and after changes as well as between-group differences in change scores were compared. Furthermore, multivariate linear regression analysis was performed to examine whether exercise intensity was independently associated with changes in dietary intake and leptin.

Of the 69 participants, 55 completed the study and were included in the analysis. Dietary intake increased significantly from 1367 to 1484 kcal/day (p = 0.01), whereas leptin did not change significantly in the overall cohort. Between-group comparisons of change scores revealed a significant difference in leptin (p < 0.01) but not in dietary intake (p = 0.16). Multivariable regression analysis showed that exercise intensity attainment was associated with changes in leptin (B = -4.47, p < 0.01) but not dietary intake (p = 0.12).

Dietary intake increased following pulmonary rehabilitation in patients with COPD. Although exploratory analyses suggested an association between attainment of high-intensity exercise training and changes in leptin levels, the relationship with dietary intake remains unclear.

Chronic obstructive pulmonary disease (COPD) and periodontitis frequently coexist, but directionality and shared cellular mechanisms remain uncertain. We evaluated whether genetically proxied COPD liability is associated with periodontitis risk and explored candidate immune mechanisms.

We performed two-sample Mendelian randomization (MR) and smoking-adjusted multivariable MR (MVMR), followed by pathway enrichment and summary-data-based MR. Single-cell RNA sequencing (scRNA-seq) datasets from COPD peripheral blood and periodontitis gingiva were reanalyzed to localize implicated cell states. RAW264.7 macrophages were exposed to Porphyromonas gingivalis lipopolysaccharide (LPS, 1 μg/mL, 24 h) to assess candidate-gene responsiveness.

In univariable inverse-variance weighted MR, COPD liability was positively associated with chronic periodontitis (odds ratio [OR] 1.282, 95% confidence interval [CI] 1.097-1.499). The association persisted after adjustment for smoking initiation (OR 1.183, 95% CI 1.054-1.328) and past tobacco smoking (OR 1.235, 95% CI 1.101-1.387). The conditional F-statistic for COPD was 5.02 in the smoking-initiation model, requiring cautious interpretation. Enrichment implicated major histocompatibility complex class II antigen presentation and arachidonic-acid metabolism. HSP90AA1 and ALOX15B were prioritized as candidate protective mediators. Across separate cohorts, scRNA-seq signals converged on the monocyte-macrophage lineage. LPS reduced HSP90AA1 and ALOX15B transcript abundance in RAW264.7 cells.

The findings support a smoking-adjusted genetic association, not definitive smoking-independent causality. Macrophages and the two prioritized genes represent hypothesis-generating mediators that require validation in matched human cohorts and targeted perturbation models.