Citations

Abstract Background Dermatological health-related quality of life (HRQoL) among solid organ transplant recipients (SOTRs) may be adversely affected by various factors, including skin cancer. However, there has been limited assessment of dermatological HRQoL in SOTRs. This study aimed to evaluate the impact of skin cancer on quality of life (QoL) in SOTRs and to compare HRQoL measures between SOTRs with and without skin cancer. Methods This cross-sectional study was conducted at the Mayo Clinic Florida from June 2023 to March 2024. Adult patients who underwent solid organ transplantation between June 1995 and December 2023 were assessed using the Dermatology Life Quality Index (DLQI) and Skindex-29 questionnaires. For SOTRs with keratinocyte carcinoma (KC), the Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) questionnaire was also administered. Results A total of 150 adult SOTRs were included, with 82 having developed post-transplant skin cancer, including melanoma and keratinocyte carcinomas (KC). SOTRs with skin cancer were older at first transplant (Median: 61.8 vs. 57.3 years, P = 0.0073) and had a higher proportion of males (76.8% vs. 55.9%, P = 0.0086). Fitzpatrick skin type III-VI was less prevalent (8.5% vs. 38.2%, P < 0.0001). The frequency of SCC and BCC was 92.7% and 41.5%, respectively. DLQI scores were higher in SOTRs with skin cancer, however, the difference was not statistically significant (P ≥ 0.065). SOTRs with skin cancer had higher total Skindex-29 scores (P = 0.012) and “emotion” subscale scores (P = 0.0049), indicating a negative impact on QoL. BaSQoL scores showed a moderate negative effect on QoL, with a higher number of KCs correlating with lower QoL (P < 0.05). Female gender had higher DLQI total score (P = 0.0042) and BaSQoL diagnosis and treatment (P = 0.031). Conclusions: SOTRs with skin cancer exhibited lower overall QoL, with a greater number of skin cancers linked to more pronounced negative impacts on QoL across all assessment instruments. Female gender was also associated with lower QoL scores. Recognizing the potential for reduced QoL in SOTRs is essential for developing tailored management strategies to support this population.

Abstract Progression of disease within 24 months of initial immunochemotherapy (POD24) is a negative prognostic factor for patients with follicular lymphoma (FL). There is no standard treatment after POD24. Assembling an academic-based cohort from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence, we evaluated patterns of care and outcomes for 220 patients with FL with POD24 and retained FL histology. Therapy after POD24 was heterogeneous, with no treatment category accounting for &gt;25% of the total. Among patients initially treated with bendamustine-rituximab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was the predominant second-line choice (48%). Among patients initially treated with R-CHOP, aggressive salvage therapy was the predominant second-line choice (38%). Overall response rate to therapy after POD24 was 64% (95% confidence interval [CI], 56-70); complete response rate was 39% (95% CI, 32-46). The median event-free survival for therapy after POD24 was 9.8 months (95% CI, 7.3-12.1); 5-year overall survival (OS) was 71% (95% CI, 65-78). OS was inferior for patients aged &gt;70 years (hazard ratio [HR], 2.31; 95% CI, 1.27-4.20) and those with high-risk FL International Prognostic Index scores at diagnosis (HR, 2.10; 95% CI, 1.23-3.60). No treatment category stood out with more favorable results. Cause of death was predominantly lymphoma related. Patients with follicular histology at their POD24 event had a low cumulative incidence of transformation (1.1% at 5 years). Our study is among the largest cohorts describing contemporary patterns of care for patients with POD24, providing a focused data set useful for interpreting and designing prospective clinical trials in this population.

Background: Spontaneous coronary artery dissection (SCAD) is a rare and often underdiagnosed cause of acute coronary syndrome (ACS), predominantly affecting younger women without traditional cardiovascular risk factors. The management of SCAD remains a subject of debate, likely secondary to inconclusive evidence. This study aims to compare the clinical outcomes of SCAD patients treated with optimal medical therapy (OMT) versus those who underwent percutaneous coronary intervention (PCI) using a national population-based cohort. Methods: We conducted a retrospective analysis using the National Inpatient Sample (NIS) database from 2016 to 2020. The study included patients identified with SCAD using the ICD-10-CM (the International Classification of Diseases, Tenth Revision, Clinical Modification) code I25.42. We excluded individuals who did not receive PCI or coronary angiography, those who underwent coronary artery bypass grafting, and patients with incomplete records. The primary outcome was in-hospital mortality, while secondary outcomes included acute kidney injury, cardiac arrest, cardiogenic shock, use of temporary mechanical circulatory support, cost of hospitalization, and length of stay. National estimates were obtained using discharge weights, and statistical comparisons were performed using chi-square tests and linear regression. Multivariate logistic regression was employed to identify predictors of mortality and other outcomes. Results: A total of 31,105 SCAD patients were included in the study, with 10,480 receiving OMT and 20,625 undergoing PCI. Patients in the PCI group were older (mean age 64 vs. 54 years) and had higher comorbidities compared to those in the OMT group. The proportion of SCAD patients receiving PCI declined from 72% in 2016 to 60% in 2020. In multivariable analysis, PCI was associated with increased in-hospital mortality (odds ratio (OR) 1.89, 95% confidence interval (CI) 1.24–2.90, p = 0.0003), cardiogenic shock (OR 2.29, 95% CI 1.71–3.07, p < 0.0001), use of a left ventricular assist device (LVAD) (OR 3.97, 95% CI 2.42–6.53, p < 0.0001), and an intra-aortic balloon pump (IABP) (OR 2.24, 95% CI 1.63–3.09, p < 0.0001). Trends also suggested an association between PCI and cardiac arrest, extracorporeal membrane oxygenation (ECMO), and acute kidney injury (AKI). The PCI group had significantly higher hospitalization costs and longer lengths of stay compared to the OMT group (both p < 0.001). Conclusions: In this large, national cohort study, SCAD patients who underwent PCI had significantly higher risks of adverse in-hospital outcomes, including mortality, compared to those treated with OMT. These findings underscore the importance of careful patient selection and the potential advantages of conservative management in SCAD, particularly in patients without severe or unstable presentations. Further research is needed to develop evidence-based guidelines for the optimal management of SCAD.

Lipoprotein a (Lp(a)) is a lipid biomarker that binds cholesterol and bears independent cardiovascular risk. Strategies to lower the level of Lp(a) and mitigate such risk are important both for primary and secondary prevention. Currently there are no approved therapies targeting Lp(a) directly. Lipid lowering therapies prescribed routinely may have no effect on Lp(a) levels. Some agents such as niacin and estrogens can significantly decrease Lp(a), but their use is not recommended due to their adverse safety profile. Statins increase Lp(a) levels by 10–20%, questioning the benefit of such therapy when this biomarker is elevated. The Food and Drug Administration (FDA) endorses new agents to address dyslipidemia such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-i) and Inclisiran, a small interfering RNA. These approaches have been shown to also significantly reduce Lp(a), but more clinical data is needed before implementing their use in clinical practice. Clinical trials are currently ongoing to test the efficacy of newly developed antisense oligonucleotides and small interfering RNAs targeting the gene encoding for Lp(a) in hepatocytes, while other investigations assess small molecules that inhibit Lp(a) assembly. This review summarizes the pathophysiology and clinical implications of Lp(a) elevation, and focuses on proposed Lp(a) therapies and the current state of the clinical trials of such novel agents.

Abstract Aims The increasing need for diagnostic echocardiography tests presents challenges in preserving the quality and promptness of reports. While Large Language Models (LLMs) have proven effective in summarizing clinical texts, their application in echo remains underexplored. Methods and results Adult echocardiography studies, conducted at the Mayo Clinic from 1 January 2017 to 31 December 2017, were categorized into two groups: development (all Mayo locations except Arizona) and Arizona validation sets. We adapted open-source LLMs (Llama-2, MedAlpaca, Zephyr, and Flan-T5) using In-Context Learning and Quantized Low-Rank Adaptation fine-tuning (FT) for echo report summarization from ‘Findings’ to ‘Impressions.’ Against cardiologist-generated Impressions, the models’ performance was assessed both quantitatively with automatic metrics and qualitatively by cardiologists. The development dataset included 97 506 reports from 71 717 unique patients, predominantly male (55.4%), with an average age of 64.3 ± 15.8 years. EchoGPT, a fine-tuned Llama-2 model, outperformed other models with win rates ranging from 87% to 99% in various automatic metrics, and produced reports comparable to cardiologists in qualitative review (significantly preferred in conciseness (P &lt; 0.001), with no significant preference in completeness, correctness, and clinical utility). Correlations between automatic and human metrics were fair to modest, with the best being RadGraph F1 scores vs. clinical utility (r = 0.42) and automatic metrics showed insensitivity (0–5% drop) to changes in measurement numbers. Conclusion EchoGPT can generate draft reports for human review and approval, helping to streamline the workflow. However, scalable evaluation approaches dedicated to echo reports remains necessary.

Abstract Background The SUNSHINE and SUNRISE phase III trials demonstrated sustained clinical efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa (HS) through 52 weeks. Patients completing the core trials could enter a 4-year extension trial. Objectives To evaluate the long-term efficacy, safety/tolerability and maintenance of clinical response to secukinumab through week 104 in the extension trial. Methods Patients with a hidradenitis suppurativa (HS) clinical response (HiSCR) at week 52 of the core trials (extension trial baseline visit) entered a randomized withdrawal period. HiSCR responders receiving subcutaneous secukinumab 300 mg every 2 or 4 weeks (SECQ2W/SECQ4W) through week 52 in the core trials were randomized 2 : 1 to continue secukinumab (SECQ2W-R-Q2W or SECQ4W-R-Q4W) or receive placebo (SECQ2W-R-PBO or SECQ4W-R-PBO) through week 104. The primary endpoint was time to loss of response (LOR; newly defined for this trial) through week 104 in week 52 HiSCR responders (SECQ2W-R-Q2W vs. SECQ2W-R-PBO and SECQ4W-R-Q4W vs. SECQ4W-R-PBO). Time to LOR was tested at 1.25% (one-sided) for each comparison (one-sided familywise alpha of 2.5%) through week 104. If LOR was met, patients could remain in the trial on open-label secukinumab treatment. Additional endpoints included safety and HiSCR. The trial was registered with ClinicalTrials.gov (NCT04179175). Results Overall, 84.3% of patients who completed the core trials entered the extension trial; 55.9% were week 52 HiSCR responders. The primary endpoint was not met for either secukinumab dosing regimen. The estimated risk reduction for LOR was 13% (SECQ2W-R-Q2W vs. SECQ2W-R-PBO; one-sided P = 0.25) and 30% (SECQ4W-R-Q4W vs. SECQ4W-R-PBO; one-sided P = 0.04). The median time to LOR was numerically longer in the secukinumab arms vs. placebo {SECQ2W-R-Q2W [283 days; 95% confidence interval (CI) 176, –] vs. SECQ2W-R-PBO [239 days; 95% CI 120, –]; SECQ4W-R-Q4W [365 days 95% CI 225, –] vs. SECQ4W-R-PBO [171 days; 95% CI 113–337]}. In week 52 HiSCR responders reporting LOR, 44% (SECQ2W-R-Q2W), 58% (SECQ2W-R-PBO), 40% (SECQ4W-R-Q4W) and 34% (SECQ4W-R-PBO) were achieving HiSCR at the time of LOR. Overall, the safety of secukinumab was consistent with the core trials. Conclusions The primary endpoint of this trial was not met. HiSCR was maintained in many patients at the time of LOR. The safety of secukinumab was consistent with the previously characterized safety profile in the core trials.

Abstract Background Anal squamous cell carcinoma is a rare cancer with increased occurrence of multiple cancers before and after the anal squamous cell carcinoma diagnosis. However, there are limited data on this aspect. This multi-institutional analysis aimed to define the occurrence of malignancies before and after anal squamous cell carcinoma, time trends, and impact on survival and to identify prognostic factors. Methods Initial primary malignancy was defined as a malignancy occurring before the anal squamous cell carcinoma. Second primary malignancy was defined as a distinct primary cancer that developed after anal squamous cell carcinoma diagnosis. Retrospective multi-institutional chart review was done. Progression-free survival (PFS), overall survival, and prognostic factors were evaluated. Results A total of 647 patients with anal squamous cell carcinoma treated with curative intent were analyzed. Median age was 61.2 years with 72% as females. Of these, 150 (23.3%) patients had multiple malignancies with initial primary malignancy in 16% and second primary malignancy in 8%. Patients without prior cancer had better 5-year PFS (81.2% vs 67.2%, P = .011) and overall survival (81% vs 69%, P = .008) compared with those with prior cancer. Second primary malignancies had a statistically significant adverse impact on PFS (hazard ratio [HR] = 4.22) and overall survival (HR = 3.56). Females had better 5-year PFS (82% vs 70%, P = .016) as compared with males. The median time interval for developing anal squamous cell carcinoma (as second primary malignancy) after initial primary malignancy was 9.32 years. Conclusions Anal squamous cell carcinoma patients have an increased risk of multiple malignancies. These patients who have prior cancers have inferior outcomes. Second primary malignancy is a poor prognostic factor in patients with anal cancer. Second primary malignancy can develop years after treatment of primary anal squamous cell carcinoma.

An uncertainty-aware deep learning model developed using Mondrian conformal prediction demonstrated high performance in intracranial hemorrhage detection on noncontrast head CT volumes and high accuracy in identifying challenging cases.