Kocsis, S Christian

Abstract Background Radiation-induced heart disease (RIHD) may develop months to years following radiation therapy for cancers near the heart such as lung or breast cancer. Several mouse models of RIHD exist to study the pathogenesis of disease, but to our knowledge no studies have examined whether sex differences exist in RIHD in mice. Methods Female and male BALB/cJ mice received one whole heart dose of 22 Gray (Gy) radiation via a C5 collimator vs. sham controls that received 0 Gy, anesthesia and were placed in the X-ray machine for the same length of time. Mechanisms of cardiotoxicity were examined at 24 h (innate cardiotoxicity), day 10 (acute cardiotoxicity) and day 35 (chronic cardiotoxicity) post irradiation. Results Females and males developed dsDNA breaks from radiation at day 10 but females had more damage than males ( p < 0.001). Vessel area and cardiac hypertrophy were increased by radiation at day 10 and 35 but were higher in males than females at day 35 ( p < 0.001, p = 0.001, respectively). Bulk RNA sequencing of the heart at day 10 revealed that females and males developed similar gene pathway responses to radiation by upregulating cellular repair pathways and downregulated mitochondrial function. However, females upregulated the master regulator of mitochondrial function, Pgc1α ( p = 0.0001), suggesting improved mitochondrial repair in females. By day 35, males developed heart failure with reduced ejection fraction (HFrEF), inflammatory dilated cardiomyopathy (iDCM) and fibrosis while females developed heart failure with preserved ejection fraction (HFpEF) without inflammation or fibrosis. Conclusions We observed sex differences in nearly every cardiac parameter that we examined following radiation exposure. BALB/c males exposed to 22 Gy radiation developed HFrEF and iDCM by day 35 while females developed HFpEF. Further research is needed to better understand mechanisms driving sex differences in RIHD using translational animal models.

Abstract Objectives Patients with hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) experience a wide array of symptoms and system disorders. This study aimed to identify whether differences occurred in 115 self-reported symptoms and comorbidities in patients diagnosed with hEDS or HSD. Methods In this study we analysed self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS, HSD or no hypermobile conditions. Results From 1 November 2019 to 7 March 2024, the EDS Clinic saw 2088 patients. Using the 2017 diagnostic criteria, 66.5% were diagnosed with HSD (n = 1389), 20.3% with hEDS (n = 423), 10.6% with historic HSD (H-HSD) or localized HSD (L-HSD) (n = 256) (hypermobile controls) and 2.6% were not diagnosed with hEDS, HSD, H-HSD or L-HSD (n = 55) (controls). Symptoms/comorbidities that occurred with high prevalence in both hEDS and HSD included joint pain (hEDS 82.0%, HSD 88.9%), allergy (hEDS 77.0%, HSD 77.0%), subluxations (hEDS 71.2%, HSD 72.6%), brain fog (hEDS 70.0%, HSD 74.7%), headache (hEDS 68.1%, HSD 69.1%), anxiety (hEDS 60.3%, HSD 69.3%), depression (hEDS 52.2%, HSD 58.0%), migraine (hEDS 53.7%, HSD 52.5%), nausea (hEDS 54.6%, HSD 59.5%) and constipation (hEDS 53.0%, HSD 57.2%). In contrast, 9/115 (8%) symptoms/comorbidities were self-reported significantly more often in hEDS but 42/115 (37%) in HSD. hEDS patients reported more symptoms that suggest a defect in collagen, such as dislocation, hernias and rectal prolapse, while HSD patients reported more joint, muscle, allergy, neurological, gastrointestinal, sleep and psychological symptoms/comorbidities. Conclusion Although we found an overlap in some symptoms and comorbidities self-reported by hEDS/HSD patients, such as allergy/atopy, headache/migraine and gastrointestinal symptoms, our findings suggest key differences exist between the two diagnoses, suggesting that hEDS and HSD may be distinct conditions.