Original research: Patient ownership of primary biliary cholangitis long-term management

ObjectivePatient ownership of disease is vital in rare diseases like primary biliary cholangitis (PBC). This survey of UK members of the PBC foundation aimed to assess patients’ perception of their disease management, focusing on key biomarkers and problematic symptoms.DesignRegistered PBC foundation members were surveyed on their experiences on their most recent clinic visit, covering the type of hospital and clinician and whether biochemical response and symptom burden were discussed, including who initiated these conversations. Respondents were also asked about their willingness to initiate these conversations.ResultsAcross 633 respondents, 42% remembered discussing alkaline phosphatase, the key biochemical response measure, and the majority of discussions were initiated by the healthcare provider. 56% of respondents remembered discussing itch, a key PBC symptom. There was no distinction between the grade of healthcare professional, but both patients and clinicians were significantly more likely to discuss symptoms over disease progression. Reassuringly, 84% of respondents felt willing to initiate conversations about their illness, regardless of the grade of managing clinician.ConclusionsThis work lays a positive foundation for patient education and empowerment projects, likely to improve clinical outcomes. Key aspects of management (biochemical response to treatment and symptom burden) should be emphasised as topics of discussion to both patients and clinicians managing PBC. We suggest a simple cue card to prompt patient-led discussion.     

IP3 receptor orchestrates maladaptive vascular responses in heart failure

Patients with heart failure (HF) have augmented vascular tone, which increases cardiac workload, impairing ventricular output and promoting further myocardial dysfunction. The molecular mechanisms underlying the maladaptive vascular responses observed in HF are not fully understood. Vascular smooth muscle cells (VSMCs) control vasoconstriction via a Ca²⁺-dependent process, in which the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) on the sarcoplasmic reticulum (SR) plays a major role. To dissect the mechanistic contribution of intracellular Ca²⁺ release to the increased vascular tone observed in HF, we analyzed the remodeling of IP3R1 in aortic tissues from patients with HF and from controls. VSMC IP3R1 channels from patients with HF and HF mice were hyperphosphorylated by both serine and tyrosine kinases. VSMCs isolated from IP3R1^VSMC–/– mice exhibited blunted Ca²⁺ responses to angiotensin II (ATII) and norepinephrine compared with control VSMCs. IP3R1^VSMC–/– mice displayed significantly reduced responses to ATII, both in vivo and ex vivo. HF IP3R^1VSMC–/– mice developed significantly less afterload compared with HF IP3R1^fl/fl mice and exhibited significantly attenuated progression toward decompensated HF and reduced interstitial fibrosis. Ca²⁺-dependent phosphorylation of the MLC by MLCK activated VSMC contraction. MLC phosphorylation was markedly increased in VSMCs from patients with HF and HF mice but reduced in VSMCs from HF IP3R1^VSMC–/– mice and HF WT mice treated with ML-7. Taken together, our data indicate that VSMC IP3R1 is a major effector of increased vascular tone, which contributes to increased cardiac afterload and decompensation in HF.     

Fractional CO2 laser for the treatment of sclerodermatous cGVHD

ABSTRACT

Sclerodermatous graft versus host disease (sclGVHD) is a debilitating complication of hematopoietic stem cell transplant and is characterized by skin thickening and fibrosis that can result in severe contractures. While immunosuppressive therapy remains a mainstay of treatment, the disease course often progresses and, in severe cases, renders patients immobile and wheelchair-bound. Lasers that can target sclerotic lesions to improve tissue pliability and restore range of motion are a promising potential treatment for sclGVHD. Fractional CO2 lasers promote selective collagen remodeling by creating microcolumns of thermal injury that stimulate a wound healing response. Here, we present 2 patients with sclGVHD who underwent treatment with fractional ablative CO2 laser. In this pilot case series demonstrating the novel use of CO2 laser for severe, refractory sclGVHD, two patients were treated with fractional ablative CO2 laser to a focal area of sclerosis. One patient also received clobetasol ointment under occlusion in between treatments. Both patients reported marked subjective improvement in pain and mobility. Objective measurements were recorded for patient 2 who gained roughly 10 degrees of extension and 2 degrees of flexion, as well as a 10% reduction in skin thickness in the treated area. CO2 laser therapy with or without clobetasol ointment under occlusion is a promising treatment modality for sclGVHD.     

The role of bioidentical hormone replacement therapy in anti-aging medicine: a review of the literature

The changes in skin and overall appearance that occur with increasing age can be partly attributed to declining hormone levels. While hormonal deficiencies are most commonly associated with postmenopausal females, males are also subject to age-related testosterone decline and may benefit from replacement of deficient hormones. However, great disparities exist between the recommendations of scientific societies and actual use of hormone supplements in aging patients. The purpose of this literature review is to discuss the role of hormones in the aging process of the skin, explain the safety profile of hormone replacement therapy, specifically discussing the superiority of bioidentical hormones, and highlight the benefits of hormone replacement in anti-aging of the skin. In summary, this literature review suggests that hormone replacement with bioidentical hormones is a safe and effective way to prevent skin aging.     

Bridging the gap in epilepsy care: A single-center experience of 3700 outpatient tele-epilepsy visits

We describe the largest-to-date single-center implementation of tele-epilepsy. Beginning in 2017, all patients at a single tertiary care academic epilepsy center were offered the option to complete outpatient follow-up visits via video-conferencing using personal devices. A retrospective review of all patients who self-selected virtual visits over nearly 3 years showed 2140 patients completed 3698 tele-epilepsy visits, with 41% completing more than one visit during the study period. Based on the distance from the center to the home address, 26.7% of patients were local (≤50 miles), 30.5% were near regional (51-150 miles), 20.1% were far regional (151-270 miles), and 22.7% were remote (>270 miles), from 43 different states. An estimated 928 696 miles of travel was prevented, with a median travel distance saved of 124.5 miles (interquartile range = 45.0-253.0). The mean visit time was 15.7 (±10.4) minutes. More than 90% of patients gave the visit and provider experience the maximum rating, with a nearly 60% response rate on the post-visit survey. Virtual outpatient follow-up care provides a convenient way to connect with epilepsy specialists and reduce the burden of care by cutting travel time. Our experience demonstrates that outpatient tele-epilepsy is feasible, sustainable, and scalable.