Immunosuppressive drugs for patients with psoriasis during the COVID-19 pandemic era. A review.

The COVID-19 has been spreading around the world. Concerns about the safety of administration of immunosuppressive drugs have been raised for treatment of psoriasis (PSO), and there is insufficient evidence for the risk of COVID-19 infection for psoriatic patients using these drugs, so we did a review, focusing on the risk of overall infection associated with the most commonly used immunosuppressive drugs, such as methotrexate, biologics, cyclosporin, Janus kinase inhibitors for the treatment of PSO. The data on the effect of immunosuppressive drugs on this virus may be ever-changing and remains to be clear. We recommend the initiation and continuation of low-risk immunomodulating drugs, such as Interleukin (IL)-17, IL-12/23, and IL-23 inhibitors, for treatment of PSO during COVID-19 era. For psoriatic patients with comorbidities switching to safer modalities such as systemic retinoids, apremilast, and home phototherapy is recommended. Immunosuppressive drugs should be withheld in psoriatic patients with the COVID-19 infection.

Efficacy and safety of hydrogen peroxide topical solution in treating actinic keratosis: A randomized controlled trial.

Actinic keratosis (AK) is a precancerous skin lesion associated with the development of squamous cell carcinoma. Approved topical treatments for AK are unmet needs. To evaluate the safety and efficacy of hydrogen peroxide topical solution 35% (H2 O2 ) with cryosurgery for the treatment of AKs. Eligible subjects were randomly assigned to receive H2 O2 and cryosurgery on each side of their scalp/face. Patients were assessed at baseline and after 3 months of follow-up. Efficacy was evaluated based on the Actinic Keratosis Area and Severity Index (AKASI) and dermoscopic assessments. Fifteen patients with 98 lesions completed the study. At the follow-up visit, the mean improvement of AKASI from baseline was 1.7 ± 0.9 for H2 O2 and 1.7 ± 0.8 for cryosurgery (p < 0.001, both). Both treatments significantly improved dermoscopic features of yellow scale, white scale, linear-wavy vessels, pigmented dots, and rosette at the end of the 3-month follow-up. Complete dermoscopic response occurred in 57.7% and 73.9% of lesions treated with H2 O2 and cryosurgery, respectively (p > 0.05). Regarding safety, hypopigmentation occurred more frequently in the cryosurgery group (28.3% vs. 9.6%; p = 0.017). Moreover, patients endured more pain with cryosurgery application than H2 O2 (p < 0.001). The effect of H2 O2 solution was comparable to cryosurgery. This treatment was well tolerated and had a favorable safety in patients with AKs.

Multiple functions of microfluidic platforms: Characterization and applications in tissue engineering and diagnosis of cancer.

Microfluidic system, or lab-on-a-chip, has grown explosively. This system has been used in research for the first time and then entered in the clinical section. Due to economic reasons, this technique has been used for screening of laboratory and clinical indices. The microfluidic system solves some difficulties accompanied by clinical and biological applications. In this review, the interpretation and analysis of some recent developments in microfluidic systems in biomedical applications with more emphasis on tissue engineering and cancer will be discussed. Moreover, we try to discuss the features and functions of microfluidic systems.

RAS/MAPK signaling functions in oxidative stress, DNA damage response and cancer progression.

Mitogen-activated protein kinase (MAPK) signaling pathways organize a great constitution network that regulates several physiological processes, like cell growth, differentiation, and apoptotic cell death. Due to the crucial importance of this signaling pathway, dysregulation of the MAPK signaling cascades is involved in the pathogenesis of various human cancer types. Oxidative stress and DNA damage are two important factors which in common lead to carcinogenesis through dysregulation of this signaling pathway. Reactive oxygen species (ROS) are a common subproduct of oxidative energy metabolism and are considered to be a significant physiological modulator of several intracellular signaling pathways including the MAPK pathway. Studies demonstrated that the MAP kinases extracellular signal-regulated kinase (ERK) 1/2 and p38 were activated in response to oxidative stress. In addition, DNA damage is a partly common circumstance in cell life and may result in mutation, cancer, and even cell death. Recently, accumulating evidence illustrated that the MEK/ERK pathway is associated with the suitable performance of cellular DNA damage response (DDR), the main pathway of tumor suppression. During DDR, the MEK/ERK pathway is regularly activated, which contributes to the appropriate activation of DDR checkpoints to inhibit cell division. Therefore, the aim of this review is to comprehensively discuss the critical function of MAPK signaling in oxidative stress, DNA damage, and cancer progression.

Iranian guideline for rituximab therapy in pemphigus patients.

Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and/or mucosa. Rituximab (RTX) has been approved recently by US FDA as an effective and safe treatment of PV. The high incidence of PV in Iran encouraged our team to prepare a consensus guideline for RTX administration based on literature review and a decade experience of an expert panel. RTX is recommended for the treatment of new cases of PV as well as patients not responding to conventional therapy. Contraindications include history of anaphylaxis or IgE-mediated hypersensitivity to murine proteins of RTX, severe active infections, pregnancy, breastfeeding, severe heart failure, and arrhythmia. Prophylactic antiviral therapy is recommended in patients at risk of reactivation of HBV and isoniazid for those at risk of reactivation of tuberculosis. Concomitant use of systemic corticosteroids is recommended as a rule. Except for methotrexate, the combination with other immunosuppressive drugs is discouraged. Intravenous immunoglobulin is recommended for those at risk of infections or with extensive disease. The recommended dosage of RTX for the first cycle is 2 g either 500 mg weekly or 1 g biweekly. There is no general consensus whether the next doses of RTX be administered upon relapse or as maintenance therapy. We strongly recommend RTX sooner in the course of pemphigus.

Treatment of port wine stains with 595-nm pulsed dye laser in 27 pediatric patients: A prospective study in the Iranian population.

Port wine stain (PWS) is a congenital vascular malformation, which is visible at the birth as the red patches, mostly on the face and neck. Previous studies have shown good efficacy and safety of 595-nm pulsed dye laser (PDL). Here, we have conducted a prospective study to assess the efficacy and safety profile of pediatrics with PWS, treated with 595-nm PDL. Twenty-seven patients (10 males and 17 females) with the mean age of 5.7 ± 2.8 (range 1-13) years old were included in the study. Following 6.2 (range 4-10) sessions of treatment, 70.74 ± 18.5% of improvement was detected three months after the final session. Fourteen (51.8%) patients achieved a higher than 75% of improvement; nine (33.4%) patients experienced 50%-75% improvement; four (14.8%) patients experienced a less than 50% improvement. V1 involvement and a marked improvement within the first five sessions found to be good prognostic factors. Regarding age, sex, skin type, color and size of the PWS, no significant association with therapeutic response were detected. Blister and crust, atrophic macules, and hyperpigmentation were noted in six (22.2%), one (3.7%), and one (3.7%), respectively. In conclusion, 595-nm PDL looks an effective and relatively safe therapeutic approach in the treatment of Iranian pediatric PWS patients.

Drug Adherence and its Association with Health Literacy Among Patients with Autoimmune Bullous Diseases.

Background: Despite the emergence of novel medications, poor drug adherence is an obstacle toward disease management in patients with autoimmune bullous dermatoses (AIBDs). Objectives: We sought to evaluate medication adherence among patients with AIBDs and determine the impact of health literacy on adherence. Methods: We performed a cross-sectional survey of patients with AIBDs who attended Razi Hospital from May to October 2021. Drug adherence and health literacy were assessed using the Morisky Medication Adherence Scale-8 (MMAS-8; scored 0-8) and Health Literacy for Iranian Adults (HELIA; scored 0-100) questionnaires, respectively. Multivariable ordinal regression, including the covariates age, sex, education level, and annual income, were employed for analyses. Results: Two hundred participants with a mean±standard deviation (SD) age of 50.3±13.5 years were recruited. The female:male ratio was 1.2. About half (53%) of the patients reported good adherence (MMAS-8 score of 8) to their AIBD medications. Moreover, limited health literacy, with a mean±SD score of 57.8±25.8, was noted. Multivariable ordinal regression indicated that literacy score was significantly associated with good drug adherence (odds ratio [OR]: 0.11 per 1 score of health literacy increase, 95% confidence interval [CI]: 0.09-0.14). Conclusion: These findings showed suboptimal drug adherence and health literacy of patients with AIBDs. Improving patient health literacy might be a way to increase drug adherence.

Anatomic evaluation of the normal variants of the arteries of face using color Doppler ultrasonography: Implications for facial aesthetic procedures.

BACKGROUND: Knowledge of normal facial vascular variations could prevent catastrophic complications of cosmetic procedures as well as providing a guide for surgical planning. Color Doppler ultrasound is a safe and noninvasive method for real time vascular evaluation. OBJECTIVE: The aim of this study was to evaluate the normal variations of the facial, angular, transverse facial, supratrochlear and supraorbital arteries in a sample of normal individuals. METHODS: Normal individuals referred for dermal filler injection to the tertiary dermatologic center, were selected. Patients who were smoker or had a history of facial filler injection, facial surgery, or trauma were excluded from the study. Facial artery at three levels as well as angular, supratrochlear, supraorbital, and transverse facial arteries were evaluated by an 18 MHz ultrasound linear probe regarding their distance from facial reference lines and landmarks, and also their depths in various regions of face. RESULTS: A total number of 43 individuals were evaluated in this study. Thirty-one (72.1%) were women. The number of absent facial artery was zero in level one, three (3.48%) in level two, and nine (10.46%) in level three. The angular artery was absent in 10 (11.62%) participants. The transverse facial artery was absent in 27 (31.39%) assessed individuals. Distance from reference lines at level 2 and 3 of facial artery and its depth at level 2 were significantly different between left and right side (p-values: <0.001, 0.01, and 0.03, respectively). No significant difference was seen between depth and distance of two sides for angular and transverse facial arteries. The comparison of the depths and distances from the reference lines of the assessed arteries between two sexes revealed only a significantly greater value of facial artery distance in level 1 in males (p-value: 0.001). BMI was also significantly correlated with the depth of facial artery in level 2 (Pearson correlation coefficient = 0.471, p-value = 0.002) and level 3 (Pearson correlation coefficient = 0.357, p-value = 0.03) and the distance of the facial artery in level 1 (Pearson correlation coefficient = 0.333, p-value = 0.029). CONCLUSIONS: Color Doppler ultrasound could be used to map the arteries of face to prevent vascular complications and safely guide cosmetic procedures.

Comparison of the efficacy of intralesional triamcinolone acetonide and 5-fluorouracil tattooing for the treatment of keloids.

BACKGROUND: Hypertrophic scars and keloids may complicate wound healing secondary to trauma or surgery. A variety of treatment regimens have been used for treatment of keloids. OBJECTIVE: To compare 5-fluorouracil (5-FU) tattooing and intralesional steroid for treatment of keloids. METHODS: In this 44-week, double-blind, clinical trial, 40 patients were randomized into two study groups. Patients in group 1 were given intralesional triamcinolone acetonide (TAC), and patients in group 2 were treated with 5-FU tattooing; both groups received treatment every 4 weeks for 12 weeks. Lesions were assessed for erythema, pruritus, height, surface, and induration at baseline (initiation of treatment) and at weeks 4, 8, 12, 20, 28, 36, and 44. All patients had complete blood count, liver function tests, and renal function tests before treatment and at week 20. RESULTS: All the patients completed the study. At the 44-week follow-up visits, both groups showed improvement in all parameters, but improvement was more significant in the 5-FU group (p < .05). No side effect was detected in either of the groups. CONCLUSION: 5-FU tattooing was more effective than intralesional TAC for the treatment of keloids.

Multiple firm nodules in a young woman: an unusual presentation of sarcoidosis.

A 27-year-old woman presented to the dermatology department with a 1-year history of multiple asymptomatic violaceous lesions on her upper and lower extremities, trunk and abdomen. The lesions were firm on palpation. She had no other associated symptoms and the rest of the examination was unremarkable. An incisional biopsy showed multiple confluent granulomas composed of histiocytes devoid of necrosis surrounded by a rim of lymphocytes extending to the subcutaneous fat consistent with the diagnosis of subcutaneous sarcoidosis. The serum ACE assay was elevated at 134 IU/L. Other blood tests including complete blood count, renal and liver function tests, serum calcium and phosphate were within normal ranges and chest X-ray was unremarkable. Complete remission was achieved with an intralesional triamcinolone injection (10 mg/mL) for a few sessions. Subcutaneous sarcoidosis is a rare variation and its diagnosis requires a high index of suspicion.

Dermoscopic Evaluation of Longitudinal Melanonychia in Children: A Prospective Study.

BACKGROUND: Longitudinal melanonychia (LM) is a worrisome sign in both children and adults. Nail apparatus melanoma (NAM) can be related to LM, but it is very rare in children. Dermoscopic signs of benign lesions in children can be similar to melanoma; therefore, it is important to review dermoscopy of LM in children to make the best decision in performing biopsy. AIMS: Biopsy taking is very challenging in LM in children. Most lesions are benign in children. The aim of this study was to review dermoscopic signs of LM in children and compare them with adults. MATERIALS AND METHODS: In this prospective study a total of 108 LM (35 children and 73 adults) were undergone dermoscopy of LM. Dermoscopic features were compared in children and adults; both for benign lesions proven by biopsy or follow up and melanomas diagnosed histopathologically. RESULTS: Black background, black band color, band color diversity and pseudo-Hutchinson's sign were more frequent in children in comparison with benign adult melanonychia. Some children's dermoscopic features of LM such as broad band width, Band color diversity, Hutchinson's sign, gray band color, asymmetry of pattern, and regression were similar to melanoma, but we did not find any melanoma by biopsy and/or follow up among children. We also detected the newly described "zigzag" pattern in four children. CONCLUSION: Dermatologists should consider all dermoscopic features of a lesion, dermoscopic sign changes in follow-up, medical, and familial history of the patient in deciding to perform biopsy of LM in children.

Design and fabrication of clinoptilolite-nanohydroxyapatite/chitosan-gelatin composite scaffold and evaluation of its effects on bone tissue engineering.

The aim of this study was to synthesize an innovative composite scaffold, which structured of clinoptilolite-nanohydroxyapatite/chitosan-gelatin (CLN-nHA/CS-G) with enhanced attributes for utilization in the bone tissue engineering. This composite scaffold was prepared by blending the CLN, nHA, chitosan, and gelatin solution followed by a freeze-drying step. The fabricated composite scaffolds were studied using BET, FTIR, XRD, and SEM techniques. The highly porous composite scaffolds with a pore size of 200 ± 100 µm were synthesized. Moreover, the effects of CLN and nHA on the physicochemical features of the scaffold such as density, swelling ratio, biomineralization, biodegradation, and mechanical behavior were studied. Compared with CS-G scaffold, the presence of CLN and nHA leads to an increased surface area, increased biomineralization, and low rate of degradation in simulated body fluid solution (SBF) and mechanical strength. Cytotoxicity of the CLN-nHA/CS-G scaffold was studied by MTT assay on human dental pulp stem cells (h-DPSCs). The biological response of h-DPSCs showed no toxicity and studied cells proliferated and attached on the pore surfaces of the scaffold. Results indicated that introducing CLN and nHA to composite improves the scaffold characteristics in a way that makes it suitable for bone tissue engineering.

A Case of Linear IgA Bullous Dermatosis Induced by Aspirin Therapy.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disease that may be triggered by some diseases and medications. For the latter one, non-steroidal anti-inflammatory drugs (NSAIDs) have been identified as one of the potential causative agents to develop LABD. Here, a rare case of drug-induced LABD is introduced. A 13-month-old Iranian boy presented with a history of generalized blisters, displaying the classic "string of pearls" sign who was eventually diagnosed as a case of LABD. In his admission, he was diagnosed whit Mucocutaneous lymph node syndrome and treated with aspirin.  Some features like appearing the characteristic lesions one week following the administration of aspirin, rapid clearance of lesions after the withdrawal of the drug, and reappearance of new lesions after readministration of aspirin were highly suggestive of aspirin-induced LABD. To establish the diagnosis, we used the "Naranjo probability score" which determined the probable causative role of aspirin. The diagnosis was confirmed by showing the positive IgA deposition in the basement membrane zone in a direct immunofluorescence study of the skin biopsy. The child was treated with dapsone with dramatical response to the drug.

A Rare Case of Tumoral Scleromyxedema.

Scleromyxedema is an uncommon disease, affecting the skin mainly and other internal organs sometimes, characterized by fibroblasts proliferation, fibrosis, and mucous deposition in the absence of thyroid disorder. It is associated with monoclonal gammopathy in most cases. We are reporting a case with a rare presentation of tumoral scleromyxedema in the neck, with a mass mimicking other tumoral lesions, highlighting the importance of diagnosis and histopathologic correlation.

Nano-hydroxy apatite/chitosan/gelatin scaffolds enriched by a combination of platelet-rich plasma and fibrin glue enhance proliferation and differentiation of seeded human dental pulp stem cells.

The purpose of this study was to investigate the effects of Fibrin Glue (FG) and activated platelet-rich plasma (a-PRP) on the proliferation and osteogenic differentiation of human dental pulp stem cells (h-DPSCs). Therefore, we planned to investigate in vitro behavior of porous composite scaffolds based on chitosan-gelatin/nanohydroxyapatite (CS-G/nHA) treated with FG and a-PRP. The porous structure of CS-G/nHA was prepared using combination of particle leaching and freeze-drying methods. The a-PRP was prepared from the centrifugation of whole blood activated with calcium chloride. Four groups of composite scaffolds were fabricated to seed h-DPSCs: (1) a-PRP-FG/CS-G/nHA; (2) FG/CS-G/nHA; (3) a-PRP/CS-G/nHA; (4) CS-G/nHA. The 14 days SEM image reveled organized fibrin network on scaffolds surface. All groups treated with FG and a-PRP, showed improved adhesion of seeded h-DPSCs compared to CS-G/nHA. Cytotoxicity of the composite scaffolds was assessed by MTT. Alizarin red staining confirmed the formation of bone minerals by h-DPSCs after 21 days of cell seeding. In addition, the a-PRP-FG treated scaffolds exhibited significantly elevated bone gamma-carboxyglutamic acid-containing protein (BGLAP), bone morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (RUNX2) gene expression. The present result the composite scaffolds treated with FG and a-PRP showed a fibrin network, preferentially on the surface of composite scaffold increasing the mineralization and osteoblastic differentiation of harvested cells. In addition, a-PRP-FG/ CS-G/nHA scaffold increased bone marker gene expressions from day 7 to day 21.

Therapeutic targeting of angiogenesis molecular pathways in angiogenesis-dependent diseases.

Angiogenesis is a critical step in the progression of almost all human malignancies and some other life-threatening diseases. Anti-angiogenic therapy is a novel and effective approach for treatment of angiogenesis-dependent diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. In this article, we will review the main strategies developed for anti-angiogenic therapies beside their clinical applications, the major challenges, and the latest advances in the development of anti-angiogenesis-based targeted therapies.

Enhanced osteogenic differentiation of mesenchymal stem cells on metal-organic framework based on copper, zinc, and imidazole coated poly-l-lactic acid nanofiber scaffolds.

The presence of inorganic bioactive minerals with polymers can accelerate and promote several processes including: bone cell joining, proliferation, differentiation, and expression of osteogenic proteins. In this study, zinc (Zn), copper (Cu), and imidazole metal-organic framework (MOF) nanoparticles were synthesized and coated over poly-l-lactic acid (PLLA) nanofibrous scaffolds for bone tissue engineering application. The surface and bioactive features of the scaffolds were characterized. The osteogenic potential of the scaffolds on human adipose tissue-derived mesenchymal stem cells (MSCs) was evaluated. Zn-Cu imidazole MOF coated PLLA scaffolds (PLLA@MOF) showed a comparable rate of MSC proliferation with the pure PLLA scaffolds and tissue culture plate (TCP). However, the PLLA@MOF potential of osteogenic differentiation was significantly greater than either pristine PLLA scaffolds or TCP. Hence, coating Zn-Cu imidazole MOF has a significant effect on the osteogenesis of MSC. Therefore, PLLA@MOF is novel scaffolds with bioactive components which are crucial for osteoconductivity and also able to provoke the osteogenesis and angiogenesis.

A Case Report of Paraneoplastic Pemphigus Associated With Retroperitoneal Inflammatory Myofibroblastic Tumor.

Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms, both malignant and benign. The most constant clinical presentation of PNP is the presence of intractable stomatitis. Herein we present a 25-year-old male with a 3-month history of refractory stomatitis especially involving the lips and widespread vesiculobullous eruption on his trunk and extremities. The diagnosis of PNP was confirmed based on histological and serological results. Investigation for the underlying neoplasm revealed a retroperitoneal tumorous mass which was biopsied and diagnosed as the inflammatory myofibroblastic tumor (IMT). The tumor was surgically excised, and different treatment regimens were used to treat the mucocutaneous lesions. Skin lesions responded favorably to treatment, but oral stomatitis still persists which is the case in most PNP patients. This combination of PNP and IMT has rarely been reported in the literature. Treatment started with corticosteroid and rituximab then tumor excised.

Rituximab therapy improves recalcitrant Pemphigus vulgaris.

Pemphigus is a severe life-threatening blistering disease associated with autoantibodies against cell adhesion proteins desmogleins 1 and 3. Patients with severe pemphigus commonly show high rates of relapse after conventional immunosuppressive therapy. The newly developed drug Rituximab showed impressing promises in the treatment of refractory pemphigus vulgaris (PV). In the present study the efficacy of a single course rituximab therapy in the treatment of PV was investigated. Eighteen patients with severe recalcitrant PV were recruited to this study. Pemphigus disease activity index (PDAI), anti-desmoglein 1 and anti-desmoglein 3 antibody titers, and percent of CD20 positive cells were measured at baseline, 10 ± 1, and 22 ± 2 weeks after rituximab therapy. Rituximab was given intravenously at dose 375 mg/m(2) once weekly for 4 weeks. Rituximab therapy caused a dramatic reduction in the PDAI, accompanied by decreases in anti-desmoglein 1 and anti-desmoglein 3 antibody titers over the follow-up course. The B-cell population decreased at the first follow-up, but returned to its baseline levels at the second follow-up. Rituximab therapy decreased the dose of immunosuppressive drugs required to control the disease. It seems that the rituximab may be effective and safe for treatment of refractory PV.