Darier disease is associated with neurodegenerative disorders and epilepsy.

Darier disease (DD) is a rare monogenetic skin disorder with limited data on its potential association with neurological disorders. This study aimed to investigate the association between DD and neurological disorders, specifically Parkinson's disease, dementias, and epilepsy. Using Swedish national registers in a period spanning between 1977 and 2013, 935 individuals with DD were compared with up to 100 comparison individuals each, randomly selected from the general population based on birth year, sex, and county of residence at the time of the first diagnosis of DD. Individuals with DD had increased risks of being diagnosed with Parkinson's disease (RR 2.1, CI 1.1; 4.4), vascular dementia (RR 2.1, CI 1.0; 4.2), and epilepsy, (RR 2.5, CI 1.8; 3.5). No association of DD with other dementias were detected. This study demonstrates a new association between DD and neurodegenerative disorders and epilepsy, underlining the need for increased awareness, interdisciplinary collaboration, and further research to understand the underlying mechanisms. Early identification and management of neurological complications in DD patients could improve treatment strategies and patient outcomes. The findings also highlight the role of SERCA2 in the pathophysiology of neurological disorders, offering new targets for future research and potentials for novel treatments.

Hailey-Hailey Disease is Associated with Diabetes: A Population-based Cohort Study, Clinical Cohort Study, and Pedigree Analysis.

Hailey-Hailey disease is a rare hereditary skin disease caused by mutations in the ATP2C1 gene encoding the secretory pathway Ca2+/Mn2+-ATPase 1 (SPCA1) protein. Extracutaneous manifestations of Hailey-Hailey disease are plausible but still largely unknown. The aim of this study was to explore the association between Hailey-Hailey disease and diabetes. A population-based cohort study of 347 individuals with Hailey-Hailey  disease was performed to assess the risks of type 1  diabetes and type 2 diabetes, using Swedish nationwide registries. Pedigrees from 2 Swedish families with Hailey-Hailey disease were also investigated: 1 with concurrent type 1 diabetes and HLA-DQ3, the other with type 2 diabetes. Lastly, a clinical cohort with 23 individuals with Hailey-Hailey disease and matched healthy controls was evaluated regarding diabetes. In the register data males with Hailey-Hailey disease had a 70% elevated risk of type 2 diabetes, whereas no  excess risk among women could be confirmed. In both pedigrees an unusually high inheritance for diabetes was observed. In the clinical cohort, individuals with Hailey-Hailey disease displayed a metabolic phenotype indicative of type 2 diabetes. Hailey-Hailey disease seems to act as a synergistic risk factor for diabetes. This study indicates, for the first time, an association between Hailey-Hailey disease and diabetes and represents human evidence that SPCA1 and the Golgi apparatus may be implicated in diabetes pathophysiology.

Effects of neoadjuvant therapy on health-related quality of life for patients with gastroesophageal cancer.

BACKGROUND: Neoadjuvant therapy in combination with surgery increases survival in gastroesophageal cancer; however, little is known about its impact on health-related quality of life. This study compared the impact of neoadjuvant therapy with that of surgery alone on the health-related quality of life in patients treated for gastroesophageal cancer. METHODS: A single-centre cohort study with prospectively collected data from patients undergoing curative intended treatment for gastroesophageal cancer between 2013 and 2020 was performed. Health-related quality of life was assessed prior to surgery and patients stratified according to neoadjuvant therapy or surgery alone. The primary endpoint was self-assessed health-related quality of life, evaluated using validated cancer-specific questionnaires. A pre-specified multivariable model adjusted for age, ASA score, and clinical T- and N-stage was used. RESULTS: A total of 361 patients were included, of whom 239 (61%) were treated with neoadjuvant therapy. Patients treated with neoadjuvant therapy reported less difficulties with eating restrictions (-11.9, p = 0.005), pain (-10.9, p = 0.004), and insomnia (-12.6, p = 0.004) than patients treated with surgery alone. Patients with oesophageal cancer and neoadjuvant therapy reported less dysphagia (-16.6, p < 0.001), eating restrictions (-23.2, p < 0.001), and odynophagia (-18.0, p = 0.002) than those who underwent surgery alone. CONCLUSION: Neoadjuvant therapy was associated with a significant reduction in symptoms affecting malnutrition and improved health-related quality of life in patients with gastroesophageal cancer. These results indicates that more patients might be available for neoadjuvant therapy, despite the baseline burden of gastroesophageal cancer.

Topical oxygen treatment relieves pain from hard-to-heal leg ulcers and improves healing: a case series.

Managing painful hard-to-heal leg ulcers is challenging with current therapeutic options. Wounds are prone to being hypoxic, and the subsequent pain is often related to hypoxia. Hyperbaric oxygen therapy (HBOT) is used to treat hard-to-heal leg wounds by delivering 100% oxygen at a pressure 2-3 times higher than atmospheric pressure. Unfortunately, most patients cannot be offered HBOT because it is costly and needs to be applied at specialised centres. Therefore, topical continuous oxygen therapy (TCOT) is a novel alternative for continuous local oxygen delivery to wounds and is associated with improved wound healing; however, its effect on painful wounds is unknown. This retrospective study was conducted on 20 patients, of whom 17 had painful hard-to-heal leg ulcers. In 13 patients (76%) with painful ulcers, TCOT was associated with rapid and substantial pain alleviation. Also, eight (40%) of the patients' wounds healed entirely with TCOT. This study suggests that TCOT may represent a novel pain management device for hard-to-heal wounds.

Topical oxygen treatment relieves pain from hard-to-heal leg ulcers and improves healing: a case report.

Pain from hard-to-heal wounds is common and challenging to manage with current therapies. Most hard-to-heal wounds show some degree of hypoxia that impairs healing and contributes to pain. Regular oxygen therapy is given in hyperbaric oxygen chambers and is costly, time-consuming and cannot be offered to most patients. Moreover, hyperbaric oxygen therapy (HBOT) only increases tissue oxygen for a short time and is given only for a few hours per week. Topical oxygen therapy (TOT) was introduced as an alternative and in this report we focus on topical continuous oxygen therapy (TCOT), which has been shown to be associated with healing of hard-to-heal ulcers. We report on a patient with type 1 diabetes with a painful hard-to-heal lower leg ulcer that failed to heal with standard wound dressings and that had insufficient response to pharmacological analgesia. The patient was on three different analgesics before treating the wound with TCOT. As the wound was considered hypoxic, due to longstanding diabetes and probable microangiopathy, TCOT was commenced. Within one week of treatment starting, the patient spontaneously ceased all his analgesics as he was free of pain; and after 2.5 months, the ulcer healed. The patient reported no adverse effects. In addition to promoting healing, TCOT may also be considered for its potential analgesic effects in hard-to-heal wound management.