Topical proactive therapy in dermatology. A scoping review.

The term 'proactive therapy' refers to a long-term management of clinically intact skin in previously disease-affected areas. This method was initially implemented in atopic dermatitis to maintain the remission and decrease the risk of exacerbations. Proactive therapy aims to limit the need for reactive treatment and improve the patients' quality of life. A proactive approach is likely to be adopted for other relapsing and inflammatory skin conditions in the future. This scoping review aims to identify dermatological conditions to be treated with the proactive approach, evaluate the available evidence for its efficacy and safety, as well as highlight the research gaps.

The Clinical Significance of Salusins in Systemic Sclerosis-A Cross-Sectional Study.

Background: Systemic sclerosis (SSc) is a connective tissue disease manifesting with progressive fibrosis of the skin and internal organs. Its pathogenesis is strictly associated with vascular disfunction and damage. Salusin-α and salusin-ß, endogenous peptides regulating secretion of pro-inflammatory cytokines and vascular smooth muscle proliferation, may potentially play a role in SSc pathogenesis. Objectives: The aim of this study was to assess the concentration of salusins in sera of patients with SSc and healthy controls and to evaluate correlations between the salusins levels and selected clinical parameters within the study group. Materials and methods: 48 patients with SSc (44 women; mean age, 56.4, standard deviation, 11.4) and 25 adult healthy volunteers (25 women; mean age, 55.2, standard deviation, 11.2) were enrolled. All patients with SSc were treated with vasodilators and twenty-seven of them (56%) also received immunosuppressive therapy. Results: Circulating salusin-α was significantly elevated in patients with SSc in comparison to healthy controls (U = 350.5, p = 0.004). Patients with SSc receiving immunosuppression had higher serum salusin-α concentrations compared with those without immunosuppressive therapy (U = 176.0, p = 0.026). No correlation was observed between salusins concentrations and skin or internal organ involvement parameters. Conclusions: Salusin-α, a bioactive peptide mitigating the endothelial disfunction, was elevated in patients with systemic sclerosis receiving vasodilators and immunosuppressants. Increased salusin-α concertation may be associated with the initiation of atheroprotective processes in patients with SSc managed pharmacologically, which requires verification in future studies.

Immunopathogenesis of Atopic Dermatitis: Focus on Interleukins as Disease Drivers and Therapeutic Targets for Novel Treatments.

Atopic dermatitis is a chronic, recurrent inflammatory skin disorder manifesting by eczematous lesions and intense pruritus. Atopic dermatitis develops primarily as a result of an epidermal barrier defect and immunological imbalance. Advances in understanding these pathogenetic hallmarks, and particularly the complex role of interleukins as atopic dermatitis drivers, resulted in achieving significant therapeutic breakthroughs. Novel medications involve monoclonal antibodies specifically blocking the function of selected interleukins and small molecules such as Janus kinase inhibitors limiting downstream signaling to reduce the expression of a wider array of proinflammatory factors. Nevertheless, a subset of patients remains refractory to those treatments, highlighting the complexity of atopic dermatitis immunopathogenesis in different populations. In this review, we address the immunological heterogeneity of atopic dermatitis endotypes and phenotypes and present novel interleukin-oriented therapies for this disease.

EGFR inhibitor-induced folliculitis decalvans: a case series and management guidelines.

Epidermal growth factor receptor (EGFR) is one of therapeutic targets in oncology for solid tumors originating from epithelial tissue, such as non-small-cell lung carcinoma (NSCLC) and breast cancer. EGFR inhibitors used in cancer treatment may cause a broad spectrum of dose-dependent cutaneous adverse events, including acneiform papulopustular rash, nail and hair disturbances, xerosis, and mucositis. The pathogenesis of the EGFR inhibitor-induced adverse reactions originates from disturbances in keratinocyte differentiation, cytokine secretion, and neutrophil chemotaxis. One of the rare, yet distressing adverse events may be folliculitis decalvans, a progressive neutrophil-driven scarring alopecia with hair tufts formation resembling doll's hair. Early diagnosis and introduction of treatment are crucial for disease prognosis since a long course of the disease leads to decreased quality of life. Here, we review the literature cases of EGFR inhibitor-induced folliculitis decalvans and provide guidance on management and prevention of this condition in oncologic patients. Furthermore, we report the first afatinib-associated folliculitis decalvans in three female patients with NSCLC.

The Role of the Cutaneous Mycobiome in Atopic Dermatitis.

Atopic dermatitis is a chronic inflammatory skin disorder characterized by eczematous lesions, itch, and a significant deterioration in the quality of life. Recently, microbiome dysbiosis has been implicated in the pathogenesis of atopic dermatitis. Changes in the fungal microbiome (also termed mycobiome) appear to be an important factor influencing the clinical picture of this entity. This review summarizes the available insights into the role of the cutaneous mycobiome in atopic dermatitis and the new research possibilities in this field. The prevalence and characteristics of key fungal species, the most important pathogenesis pathways, as well as classic and emerging therapies of fungal dysbiosis and infections complicating atopic dermatitis, are presented.

Peritoneal dialysis catheter removal at the time or after kidney transplantation: a systematic review and meta-analysis.

PURPOSE: An increasing number of patients treated with peritoneal dialysis eventually undergo kidney transplantation. Owing to opposing reports, we aimed to find evidence about the best time for peritoneal dialysis catheter removal in transplant patients. METHODS: We conducted a systematic review and random effects meta-analysis of non-randomized studies of intervention comparing patients with peritoneal dialysis catheters left in place or removed during kidney transplantation in regard to the need for dialysis and occurrence of catheter-related complications. We searched (last update on 8 December 2021) PubMed, Embase, Scopus, and Web of Science for eligible studies. ROBINS-I tool and funnel plot asymmetry analysis were used to assess the quality of included articles. RESULTS: Eight observational studies were evaluated. Five of them, which involved 338 patients, were included in a meta-analysis. All were at moderate to serious risk of bias. The odds of needing dialysis are more than twice as high for patients with peritoneal dialysis catheters left in situ (pooled odds ratio, 2.21; 95% confidence interval [CI], 1.03 to 4.73; I2 = 0%). No statistically significant difference was noted when adult and pediatric subgroups were compared (Q = 0.13, P = .720). More individuals with catheters left in place required dialysis (pooled prevalence, 20.9%; 95% CI, 13.6 to 30.7%; I2 = 59% vs. 12.4%; 95% CI, 5.6 to 25.2%; I2 = 0%) and experienced catheter-related infections. CONCLUSION: Available evidence is scarce. Unless new data from a randomized controlled trial are available, the dilemma of peritoneal dialysis catheter removal cannot be solved. TRIAL REGISTRATION: PROSPERO Protocol ID: CRD42020207707.

Platelets in Fetal Growth Restriction: Role of Reactive Oxygen Species, Oxygen Metabolism, and Aggregation.

Fetal growth restriction (FGR) is mainly caused by failure of the uteroplacental unit. The exact pathogenesis remains unclear. The cause is thought to be related to abnormal platelet activation, which may result in microthrombus formation in the small vessels of the placenta. Reactive oxygen species (ROS) may initiate the pathological process of platelet activation. This study aimed to evaluate selected platelet parameters in pregnancy complicated by FGR and relate them to the severity of hemodynamic abnormalities. A total of 135 women (pregnant with FGR, with an uncomplicated pregnancy, and non-pregnant) were enrolled to study different platelet parameters: count (PLT), mean volume (MPV), ROS levels, intracellular oxygen level, oxygen consumption, and aggregation indices. No abnormalities in PLT and MPV were found in the FGR group, although it revealed increased ROS levels in platelets, lower platelet oxygen consumption, and intraplatelet deprivation. Aggregation parameters were similar as in uncomplicated pregnancy. No significant relationships were observed between hemodynamic abnormalities and the studied parameters. Platelets in pregnancies complicated by FGR may reveal an impaired oxidative metabolism, which may, in turn, lead to oxidative stress and, consequently, to an impaired platelet function. This study adds to the understanding of the role of platelets in the etiology of FGR.

Local, non-systemic, and minimally invasive therapies for calcinosis cutis: a systematic review.

Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is available about the feasibility and efficacy of therapies alternative to systemic treatment and surgical excision, both of which often lead to unsatisfactory results or complications. We conducted a systematic review to evaluate the efficacy and safety of topical and intralesional sodium thiosulfate, extracorporeal shock-wave lithotripsy (ESWL), and laser for calcinosis cutis. PubMed, Embase, and Web of Science were searched. Reports of calciphylaxis and treatment combined with systemic medications were excluded. A total of 40 studies including 136 patients were analysed. Partial or complete remission after monotherapy was observed in 64% to 81% of cases. Self-applied topical sodium thiosulfate required patient's adherence (mean treatment duration, 4.9 months; range 2-24). Laser therapy enabled complete remission of microcalcifications after a single procedure (57%; 12/21). ESWL and intralesional sodium thiosulfate injections decreased calcinosis-associated pain (median reduction in VAS score, 3; range 0-9 and 1; range 0-5, respectively). The most common adverse event was scarring and hyperkeratosis, observed after CO2 laser (56%; 10/18). Intralesional sodium thiosulfate injections caused transient pain in over 11% of patients. Recurrences within the follow-up were rare (2%; 3/136). This study provides an overview of minimally invasive and local therapies that in selected cases might transcend conventional treatment. The limitation of this study is the poor level of evidence, which emerges mainly from non-randomized studies at high risk of bias.

Prophylactic intra-abdominal drainage following kidney transplantation: a systematic review and meta-analysis.

INTRODUCTION: An ongoing debate concerns the need for routine placement of prophylactic intra-abdominal drains following kidney transplantation. <br/><br/>Aim: We conducted a systematic review and meta-analysis to determine whether such an approach brings any advantages in the prevention of perirenal transplant fluid collection, surgical site infection, lymphocele, hematoma, urinoma, wound dehiscence, graft loss, and need for reoperation. <br/><br/>Methods: We conducted a random-effects meta-analysis of non-randomized studies of intervention comparing drained and drain-free adult renal graft recipients regarding perirenal transplant fluid collection and other wound complications. ROBINS-I tool and funnel plot asymmetry analysis were used to assess the risk of bias. <br/><br/>Results: Five studies at moderate to critical risk of bias were included. A total of 2094 renal graft recipients were evaluated. Our analysis revealed no significant differences between drained and drain-free patients regarding perirenal transplant fluid collection (pooled odds ratio [OR], 0.77; 95% confidence interval [CI], 0.28-2.17; I 2 = 72%), surgical site infection (OR, 1.64; 95% CI, 0.11-24.88; I 2 = 80%), lymphocele (OR, 0.61; 95% CI, 0.02-15.27; I 2 = 0%), hematoma (OR, 0.71; 95% CI, 0.12-3.99; I 2 = 71%), and wound dehiscence (OR, 0.75; 95% CI, 0.21-2.70; I 2 = 0%). There was insufficient data concerning urinoma, graft loss, and need for reoperation. <br/><br/>Conclusions: The available evidence is weak. Our findings show that the use of intra-abdominal drains after kidney transplantation seems to have neither beneficial nor harmful effects on perirenal transplant fluid collection and other wound complications. The present study does not support the routine placement of surgical drains after kidney transplantation. <i>In this systematic review and meta-analysis we summarize the most up-to-date evidence for and against the routine use of intra-abdominal drain following renal transplantation.</i>.

Outcomes of ex vivo liver resection and autotransplantation: A systematic review and meta-analysis.

BACKGROUND: Many patients with hepatic tumors cannot benefit from resection owing to the difficult anatomic sites of their lesions. Some of these patients might be eligible for ex vivo liver resection and autotransplantation. This procedure consists of complete hepatectomy, extracorporeal liver resection, and autotransplantation of the remnant liver. METHODS: Four databases were searched for studies reporting cases of ex vivo liver resection and autotransplantation. Outcomes of this procedure were evaluated by meta-analysis of proportions with random effects model and individual participant data analysis. RESULTS: Fifty-three studies were assessed. Meta-analysis revealed an R0 resection rate of 93.4% (95% confidence interval: 81.0-97.9%, I2 = 0%), a frequency of major surgical complications of 24.5% (95% confidence interval, 16.9-34.3%, I2 = 26%), a 30-day mortality of 9.5% (95% confidence interval: 5.9-14.9%, I2 = 0%), and a 1-year survival of 78.4% (95% confidence interval: 62.2-88.8%, I2 = 64%). We were able to obtain the individual participant data in 244 patients; R0 resection was achieved in 98.6%, with no obvious difference between analyzed subgroups. The 30-day mortality and 1-year survivals were 7.9% and 82.1%, respectively. For groups with malignant and nonmalignant tumors, the 30-day mortalities were 11.3% vs. 6.3% (P = .181), and 1-year survivals were 65.0% vs. 89.7% (P < .001). When comparing those with malignant versus those with nonmalignant lesions, major surgical complications occurred in 50.0% vs. 21.0%; P < .001). Regression analysis revealed that outcomes of patients with benign tumors were better compared with those with malignant tumors (1-year survival, odds ratio: 4.629; 95% confidence interval: 2.181-10.097, P < .001). CONCLUSION: Ex vivo liver resection and autotransplantation facilitates radical treatment in selected patients with conventionally unresectable hepatic tumors and normal liver function. The outcomes of treatment of malignant lesions appear to be less satisfactory.

Cyclosporine With and Without Systemic Corticosteroids in Treatment of Alopecia Areata: A Systematic Review.

INTRODUCTION: Cyclosporine is commonly used in treatment for alopecia areata. It can be administered as a monotherapy or in combination with systemic corticosteroids, with various outcomes. METHODS: Efficacy of cyclosporine with and without systemic corticosteroids for alopecia areata was evaluated by a systematic review. Cochrane, EBSCOhost, Pubmed, Scopus and Web of Science databases were searched. Only studies published before January 2020 were included. RESULTS: A total of 2104 studies were initially examined, of which 14 were eligible for the systematic review. Among 340 reported cases, 213 had focal, multifocal or ophiasis form of alopecia areata, 60 were diagnosed with alopecia totalis and 67 with alopecia universalis. The mean response rate in the whole group of patients at the end of treatment was 65.00% (221/340; range 25-100%). Hair regrowth rate was higher in the group with cases of alopecia areata limited to scalp (124/165; mean 75.15%; range 40-100%) than in the cases with alopecia totalis (30/46; mean 65.22%; range 25-100%) or alopecia universalis (24/52; mean 46.15%; range 25-100%). The combined therapy with systemic corticosteroids was superior to the monotherapy (152/219; mean 69.41%; 0-80% vs. 69/121; mean 57.02%; range 6.67-100%) and had a lower recurrence rate (39/108; mean 36.11% vs. 34/46; mean 73.91%, respectively). The combined treatment with methylprednisolone was significantly more effective when compared to the cyclosporine monotherapy (124/183; mean 67.76%; range 0-80% vs. 69/121; mean 57.02%; range 6.67-100%). The mean time of treatment was 6.75 months (range 2-36). LIMITATIONS: Limitations of our study were the retrospective character of included studies, differences in doses of prescribed drugs, and duration of the treatment and follow-up times. CONCLUSION: Cyclosporine in combination with oral systemic corticosteroids is more effective than in monotherapy for severe alopecia areata.

The altered platelet mineral ratios in pregnancy complicated with intrauterine growth restriction.

Altered function of maternal platelets has been evidenced in intrauterine growth restriction (IUGR) but intraplatelet burden of trace elements, factors known to affect platelet activity, remains unknown in IUGR pregnancy. This study assessed the intraplatelet status of Ca, Cu, Mg, Na, K, P, Zn and their ratios (Ca/P, Ca/Mg, Na/K, Cu/Zn) in IUGR pregnancy (n = 35), uncomplicated pregnancy (n = 25) and in non-pregnant females (n = 25). The IUGR group was characterized by the lowest content of Ca, Mg and Zn, and Ca/P ratio (<1.0), and the highest Ca/Mg and Cu/Zn ratios. The studied parameters in non-pregnant women and in uncomplicated pregnancy were comparable except P content and Ca/Mg ratio which were significantly lower in the former group. No differences in Na and K contents, and Na/K ratio between studied groups were found. This study reports that maternal intraplatelet status of selected minerals may be altered in IUGR.