Chronic lymphocytic leukemia (CLL) exhibits high remission rates after initial chemoimmunotherapy, but with relapses with treatment, refractory disease is the most common outcome, especially in CLL with the deletion of chromosome 11q or 17p. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for CLL treatment. Auranofin (Ridaura) is approved for use in treating rheumatoid arthritis, but it exhibited preclinical efficacy in CLL cells. By inhibiting thioredoxin reductase activity and increasing intracellular reactive oxygen species levels, auranofin induced a lethal endoplasmic reticulum stress response in cultured and primary CLL cells. In addition, auranofin displayed synergistic lethality with heme oxygenase-1 and glutamate-cysteine ligase inhibitors against CLL cells. Auranofin overcame apoptosis resistance mediated by protective stromal cells, and it also killed primary CLL cells with deletion of chromosome 11q or 17p. In TCL-1 transgenic mice, an in vivo model of CLL, auranofin treatment markedly reduced tumor cell burden and improved mouse survival. Our results provide a rationale to reposition the approved drug auranofin for clinical evaluation in the therapy of CLL.
The pathophysiology of hidradenitis suppurativa (HS) is not well understood. Some of our knowledge comes from clinical and epidemiological observations, along with studies of the histopathology and immunohistochemistry of affected skin. More recently, cutaneous molecular studies and transcriptomic analyses have provided additional information regarding inflammatory processes. The chronic cutaneous inflammation, systemic symptoms, and associated comorbidities suggest that HS should be classified as an immune-mediated disease, rather than a primary infectious disease. As such, a proposed integrated disease pathway is presented. At a fundamental level, there appears to be a primary abnormality in the pilosebaceous-apocrine unit, which leads to follicular occlusion, perifollicular cyst development that traps commensal microbes, and rupture into the dermis. This can trigger an exaggerated response of the cutaneous innate immune system. Initially this is an acute event, but ongoing intermittent disease activity can lead to recurrent inflammatory nodules and dermal tunnels. Once underway, the cutaneous inflammation is very difficult to turn off, leading to suppurative inflammation in whole anatomic regions. As the disease progresses, we propose that there is recruitment of the systemic immune system perpetuating the chronic cutaneous inflammatory process. There remains much to be done to understand the pathogenesis and immune signature of this challenging disease.
Although the role of immune dysregulation in hidradenitis suppurativa (HS) has yet to be elucidated, recent studies identified several complement abnormalities in patients with HS. The complement system serves a critical role in the modulation of immune response and regulation of cutaneous commensal bacteria. Complement is implicated in several inflammatory skin diseases including systemic lupus erythematosus, angioedema, pemphigus, bullous pemphigoid, and HS. A model of HS pathogenesis is proposed, integrating the role of commensal bacteria, cutaneous immune responses, and complement dysregulation. The role of complement in disease pathogenesis has led to the development of novel anticomplement agents and clinical trials investigating the efficacy of such treatments in HS.
Hidradenitis suppurativa (HS) is a complex dermatological disease characterized by recurrent painful nodules and suppuration in areas such as the axilla and groin. The disease is poorly understood and treatment is not satisfactory. In October 2016, the Canadian and United States Hidradenitis Suppurativa Foundations organized the inaugural Symposium on Hidradenitis Suppurativa Advances (SHSA) in Toronto, Canada. This meeting brought together experts from Canada, the United States, and Europe to discuss the latest advances in HS. After this important event, we considered that it would be helpful to outline current HS knowledge and to identify important gaps in treatment and research in order to move forward more efficiently. This paper briefly summarizes current knowledge in key areas including epidemiology, clinical presentation and morphological classification, natural history and prognosis, genotype-phenotype correlations, clinico-pathological correlation, pathogenesis, optimal treatment and outcome measures. General and initial suggestions for addressing these gaps are presented.
Appropriate management of both acute and chronic wounds is a dynamic practice that consumes large amounts of time and financial resources within the health care system. Traditionally, wounds were measured clinically and subjectively, leading to inaccuracies in assessing wound progression and healing over time. The recent development of mobile applications and digital equipment in medicine provides an opportunity for significant improvement in wound care through the incorporation of “smart” technologies in clinical practice. The utility of these technologies has been assessed regarding the treatment of diabetic foot ulcers, burns, and general wounds. The focus of this review is to provide an update on the current status of mobile applications and digital technology in the management of wounds.
Background
Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of hair follicles characterized by recurrent, painful nodules, abscesses, and sinus tracts (“tunnels”) typically refractory to treatment. This debilitating condition results in poor quality of life due to high disease burden. Intralesional triamcinolone (ILTAC) is a standard of care for acute inflammation and drainage associated with HS; however, the optimal therapeutic dose has not been determined. We investigated the utility of high‐dose ILTAC 20 mg/ml (ILTAC‐20) or 40 mg/ml (ILTAC‐40), for inflammatory lesions of HS.
Methods
A retrospective chart review and telephone questionnaire included HS patients treated with high‐dose ILTAC‐20 or ILTAC‐40 between April and December 2018. Patients with Hurley stages I–III were included. Data were obtained from electronic medical records and telephone interviews. A short questionnaire pertained to satisfaction with therapy, changes of disease state, and modifications in quality of life.
Results
Of 54 patients interviewed, the average age was 36.9 ± 11.6 years; 36 (66.7%) were female. Forty patients (76.9%) were very satisfied (n = 19) or satisfied (n = 21) with high‐dose ILTAC therapy. Fifty patients (92.6%) demonstrated improvements in disease state, and 41 patients (75.9%) experienced enhanced quality of life. Forty‐four patients (86.3%) were amenable to additional injections of high‐dose ILTAC, if clinically indicated. No adverse effects of therapy were reported.
Conclusions
The majority of patients reported improvements in disease state, quality of life, and overall satisfaction after administration of high‐dose ILTAC (20–40 mg/ml). These findings support the use of high‐dose ILTAC for acute lesions of HS.
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