Hodge, David O.

Purpose To explore the relationship between systemic comorbidities and presenting tumor T category in patients with uveal melanoma. Methods Single-center, retrospective cohort study of patients with posterior uveal melanoma initially diagnosed between January 2000 and December 2016. Univariate and multivariate ordinal logistic regression analyses were performed to identify comorbidities associated with presenting tumor T category, as classified by AJCC criteria. Results Initial presenting AJCC T category was T1 in 190 (43%), T2 in 130 (29%), T3 in 89 (20%), and T4 in 38 (9%). The most common comorbidities present were hypertension (250 patients, 56%), hyperlipidemia (211, 47%), obesity (137, 31%), and diabetes mellitus (87, 19%). Of these, obesity ( p = 0.034), hypertension ( p = 0.017), and diabetes mellitus ( p < 0.001) were associated with earlier presenting T category on univariate ordinal logistic regression. After multivariate regression, only diabetes mellitus ( p = 0.01) and obesity ( p = 0.04) remained significantly associated with earlier T category on initial presentation. Conclusion Among patients presenting with uveal melanoma, diabetes mellitus and obesity were associated with earlier presenting T category, which could reflect earlier detection of uveal melanoma in patients undergoing annual diabetic retinopathy screening examinations or having more frequent contact with the healthcare system. Larger studies should further explore this association and examine the utility of increased ocular screening in early detection of uveal melanoma.

Abstract Background: Although hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are inherited disorders expected to display a 1:1 sex ratio, most studies report a strong female dominance. This study analyzed sex differences in 122 self-reported symptoms and comorbidities in patients diagnosed with hEDS or HSD using the 2017 criteria. Methods: Self-reported data was obtained from November 1, 2019, to April 25, 2025, ( n =2,451) from an Intake Questionnaire of adult (≤18 years old) patients diagnosed with hEDS or HSD at the EDS Clinic at Mayo Clinic Florida and analyzed by sex. Results: We found that 90.6% ( n =575) of hEDS patients were female and 9.4% ( n =60) were male, with a sex ratio of 9.6:1 female-to-male, while 95.2% ( n =1,728) of HSD patients were female and 4.8% ( n =88) were male, with a sex ratio of 19.6:1 female-to-male. Females were older than males: hEDS 35 vs. 28 years of age ( p <0.001), HSD 34 vs. 31 years of age ( p =0.004). Overall, females self-reported more symptoms/comorbidities than males: hEDS 31/122 (25.4%), HSD 59/122 (48.4%). In contrast, only 5/122 (4.1%) symptoms/comorbidities were self-reported more often in males including attention deficit disorder/attention deficit hyperactivity disorder, delay in developmental milestones, snoring, autism spectrum disorder, and obstructive sleep apnea. Females with HSD had more mast cell-related symptoms (i.e., hives p <0.001) which were reflected in higher mast cell scores than males ( p <0.001). Patients with higher mast cell scores also had higher serum levels of total IgE ( p =0.029). More females with HSD were diagnosed with fibromyalgia ( p <0.001) and reported symptoms associated with autonomic dysfunction than males. Aside from abuse, which was higher in females (hEDS p =0.039, HSD p <0.001), few sex differences were reported for psychological symptoms/comorbidities. In support for the idea that elevated mast cell activity in females may lead to extracellular matrix remodeling that promotes hypermobility, females with hEDS/HSD had greater serum collagen-4α1 ( p <0.0001) and fibronectin ( p =0.015) than males by ELISA. Conclusions: Females with hEDS and HSD report a higher burden of symptoms/comorbidities than males, providing a possible explanation for fewer males being reported in demographic data. Sex differences in symptoms/comorbidities may reflect sex differences in pathogenic drivers of disease.

Objective: To compare the prevalence and patterns of transverse sinus stenosis (TSS) in patients with lateral skull base spontaneous cerebrospinal fluid (sCSF) leaks and idiopathic intracranial hypertension (IIH), to clarify its role in leak pathogenesis and implications for venous-directed therapies. Study design: Retrospective case-control study. Setting: Single tertiary care institution. Patients: Adults with lateral skull base sCSF leaks confirmed by clinical, laboratory, or surgical findings, and adults with IIH without cranial CSF leaks meeting Modified Dandy criteria. Intervention: Independent magnetic resonance venography evaluation by 2 fellowship-trained neuroradiologists. Main outcome measures: Presence, laterality, and severity of TSS. Results: Eighteen patients with sCSF leaks and 78 patients with IIH were included. The rate of individual TSS, including both unilateral and bilateral cases, was higher in the IIH cohort than in the sCSF leak cohort (bilateral TSS: n=66, 84.6% vs. n=6, 33.3%; P <0.001). Severe bilateral TSS was observed more in the IIH cohort (n=40, 51.3%) compared with the sCSF leak cohort (n=1, 5.6%; P <0.001). Conclusions: Though patients with lateral skull base sCSF leaks have TSS, the significantly lower rate compared with patients with IIH suggests that TSS may play a lesser role in the pathogenesis of lateral skull base defects. These findings indicate that the role of transverse sinus stenting in lateral skull base sCSF leaks remains uncertain and highlight the need to further investigate local remodeling processes when considering the role of venous sinus stenting in this population.

Abstract Background: Prophylactic-dose or low-dose apixaban and rivaroxaban have been studied in randomized controlled trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment with therapeutic anticoagulation. However, the optimal timing of dose adjustment has not been fully explored, and the rationale for a precise transition at the 6-month mark is lacking. Aim: Evaluate the clinical outcomes and demographic differences between transition to low-dose DOAC before or after the previously studied 6-month timeframe. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st, 2013 to December 31st, 2021. Patients with recurrent VTE or bleeding during the first 3 months were excluded. Patients were followed prospectively for outcomes of VTE recurrence, major bleeding, and clinically relevant non major bleeding (CRNMB), either in person or by survey. After completion of anticoagulation treatment for 3 months, the cohort of patients continuing anticoagulation with eventual transition to low-dose rivaroxaban or apixaban were evaluated. Results: A total of 466 patients were included with 167 (36%) undergoing transition to low dose prior to 6 months and 299 (64%) after 6 months of treatment. The average time to low-dose transition in the total population was 7.8 months (5.9, 3.0-55.8). The early transition group had less PE (82 versus 191, p=0.017) and significantly fewer patients with concurrent DVT and PE (32 versus 101, p=0.004). There was nearly equal representation of cancer in the two groups (34.7% versus 35.8%). Evaluation of clinical outcomes from transition time forward in the groupings before and after six months revealed no significant differences (VTE recurrence p=0.233, MB p=0.114, CRNMB p=0.745). Conclusions: This real-world patient population demonstrates that anticoagulant prescribers transition to low-dose DOACs ahead of the historically studied 6-month time point. The results of this study do not indicate a significant difference in clinical outcomes of VTE recurrence or bleeding complications based on time of transition to low-dose DOACs either before or after 6 months.

ABSTRACTObjectivesPrior studies have raised concerns about postpartum hemorrhage (PPH) risk associated with selective serotonin and serotonin‐norepinephrine reuptake inhibitors (SSRIs and SNRIs), although limitations include possible confounding by maternal indications. The current study examined the risk of PPH associated with prenatal S/NRIs accounting for diagnosed maternal depression during pregnancy.MethodsThe current study is a secondary analysis of data from a cohort of 2213 pregnancies (1997–2010) identified from a large electronic medical record‐linkage system. Exposures were identified from electronic prescriptions records and resulted in three main groups: S/NRI‐exposed pregnancies (S/NRI users), antidepressant‐unexposed pregnancies (non‐users), and S/NRI exposure in the year prior to (but not during) pregnancy (former users). Data used to identify PPH occurrences included obstetrician chart diagnoses, diagnosis codes, and recorded estimated blood loss (EBL). The risk of PPH by exposure group was estimated using unadjusted, minimally adjusted (maternal age at delivery, delivery year, parity, and maternal smoking), and depression‐adjusted models (previous covariates and maternal depression). Supplemental analyses included an examination of PPH risk with prenatal bupropion monotherapy.ResultsThe study cohort consisted of 837 S/NRI users, 401 former users, and 786 non‐users, as well as 114 bupropion users identified for additional analyses. The frequency of PPH was 11.6% in the overall cohort, and was 14.7% for S/NRI users, 10.2% for former users, and 8.7% for non‐users. The risk of PPH was significantly higher for S/NRI users than non‐users in unadjusted (OR 1.82 [95% CI 1.33, 2.49]), minimally adjusted (aOR 1.66 [1.19, 2.31]), and depression‐adjusted models (aOR 1.46 [1.02, 2.10]). The risk of PPH was also higher for S/NRI former users than non‐users in unadjusted models (OR 1.54 [1.05, 2.26]) but not minimally adjusted (aOR 1.42 [0.95, 2.11]) or depression‐adjusted models (aOR 1.41 [0.95, 2.10]). No significant differences in PPH risk were observed between S/NRI users and former users, between bupropion users and non‐users, or between S/NRI users and bupropion users.ConclusionsPrenatal S/NRI exposure was associated with an increased risk of PPH after adjusting for maternal depression, although residual confounding and confounding by other factors (including unmeasured factors) may be possible, as the risk of PPH appeared to be similar between S/NRI users and former users. Best‐practice PPH risk management strategies should be adhered to for depressed patients, especially those who require treatment with antidepressants during pregnancy.

Abstract Background Endocrine therapy has been the mainstay treatment for metastatic hormone receptor-positive / HER2-negative (HR+/HER2-) breast cancer. Given that cell cycle dysregulation and consequent uncontrolled cellular proliferation is a key mechanism behind cancer growth, agents targeting this pathway have been of major therapeutic interest.[1] The cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors palbociclib, ribociclib, and abemaciclib have shown a synergistic effect in combination with endocrine therapy.[2-3] Despite favorable results, post-approval studies have revealed potential concerns for cardiotoxicity. [4] Given this, we sought to characterize the incidence and outcomes of atrial arrhythmia among metastatic HR+/HER2- breast cancer patients who were treated with CDK 4/6 inhibitors at our institution. Purpose To investigate the incidence and risk factors of atrial arrhythmia among hormone receptor-positive/HER2-negative breast cancer patients treated with CDK4/6 inhibitors at our institution. Methods A retrospective cohort study was conducted among 2754 patients ≥18 years of age who received treatment with CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) for an established diagnosis of hormone receptor-positive, HER-2 negative breast cancer between 2015-2024. Patients with new onset atrial fibrillation and/or flutter were identified through chart review. The cumulative incidence of new-onset atrial arrhythmia was estimated using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of atrial arrhythmia. Results A total of 2754 patients was included in the study; 97.3% were female and mean age was 61 years (13). Among these, 101 (3.6%) had a prior history of atrial arrhythmia. The 1-year and 5-year cumulative incidence of new-onset AA were 1.1% and 2.8% respectively (Figure 1). When stratified by specific CDK4/6 inhibitor agents, there was no statistically significant difference. On univariable analysis, age at treatment, hypertension, coronary artery disease, and peripheral vascular disease were associated with new-onset atrial arrhythmia. However, following multivariable adjustment, only age at treatment was statistically significant. Conclusions New-onset atrial arrhythmias may occur during or after CDK4/6 inhibitor use. Older patients appeared to have a higher risk. There were no clear differences in atrial arrhythmia risk between the three CDK4/6 inhibitors.

Abstract Patients with cancer and venous thromboembolism (VTE) have higher complication rates of anticoagulation. However, studies supporting this data are relatively old reflecting the era of vitamin K inhibitors. To assess VTE recurrence, major bleeding, and clinically relevant non-major bleeding (CRNMB) in patients (March 1, 2013 to April 30, 2023) with cancer-associated VTE and patients without cancer, the prospective Mayo Clinic Thrombophilia Clinic Registry was analyzed. Over the study period, 4,711 patients with acute VTE were enrolled including 2,064 patients with cancer (mean age 62.5 ± 12.4, 46% female) and 2,647 patients without cancer (mean age 59.4 ± 16.0, 45% female). The most common cancers were gastrointestinal (n = 423, 21%), pancreatic (n = 287, 14%), and genitourinary (n = 198, 10%). Direct oral anticoagulants were used in 1,339 (65%) cancer and in 1,952 (74%) non-cancer patients. Among cancer patients, 12-month Kaplan–Meier probability of VTE recurrence was 2.4-fold greater (7.1% vs. 2.9%, p < 0.001) compared with the non-cancer group, including higher recurrent leg deep vein thrombosis (3.0% vs. 1.4%; p = 0.002) and pulmonary embolism (3.5% vs. 1.0%, p < 0.001). Patients with cancer also had 2.1-fold greater risk of major bleeding (6.3% vs. 3.0%; p < 0.001) including bleeding from the gastrointestinal tract (3.0 vs. 1.4, p = 0.01) compared with patients without cancer. Clinically relevant non-major bleeding events were similar between the groups. In this large prospective registry of VTE management, patients with cancer had significantly higher rates of VTE recurrence and major bleeding compared with patients without cancer, yet the rate of complications are substantially smaller relative to historic values of a prior vitamin K antagonist era.