Effectiveness, safety, and patient satisfaction of carboxytherapy as an adjunctive treatment for periorbital hyperpigmentation.

INTRODUCTION: Dark under-eye circles or periorbital hyperpigmentation constitute a prevalent and challenging cosmetic problem with diverse etiologies and types. While modifying exacerbating habits can provide partial relief for the pigmentary and vascular factors associated with this condition, and despite the abundance of available treatment options, there is currently a lack of gold-standard evidence-based treatments proposed for curing this disorder. OBJECTIVES: This study aimed to assess the safety and effectiveness of carboxytherapy in treating periorbital hyperpigmentation. MATERIAL AND METHODS: In this 4-week single-arm clinical trial, 20 eligible Iranian patients with symmetric periorbital hyperpigmentation received weekly intradermal carboxytherapy. The treatment involved administering 10-20 mL of CO2 at a rate of 20 mL/min and a temperature of 15°C for a duration ranging from a few seconds to 1 min. Follow-up assessments were conducted 1 month after the final session. The primary outcome was defined as the changes in ΔE or the variations in pigmentation observed between the orbital and extra-orbital skin before and after the trial. RESULTS: The patients reported satisfaction with the statistically significant reduction in hyperpigmentation achieved through carboxytherapy in the lateral (p = 0.002), middle (p = 0.001), and medial (p = 0.001) regions of the periorbital area. The total response rate of the patients was estimated at 20%. Patient satisfaction exceeded ΔE changes, with no significant linear relationship (p = 0.084). CONCLUSION: Carboxytherapy can be proposed as an effective and safe treatment for periorbital hyperpigmentation.

Obesity as an independent risk factor for COVID-19 severity and mortality.

BACKGROUND: Since December 2019, the world has struggled with the COVID-19 pandemic. Even after the introduction of various vaccines, this disease still takes a considerable toll. In order to improve the optimal allocation of resources and communication of prognosis, healthcare providers and patients need an accurate understanding of factors (such as obesity) that are associated with a higher risk of adverse outcomes from the COVID-19 infection. OBJECTIVES: To evaluate obesity as an independent prognostic factor for COVID-19 severity and mortality among adult patients in whom infection with the COVID-19 virus is confirmed. SEARCH METHODS: MEDLINE, Embase, two COVID-19 reference collections, and four Chinese biomedical databases were searched up to April 2021. SELECTION CRITERIA: We included case-control, case-series, prospective and retrospective cohort studies, and secondary analyses of randomised controlled trials if they evaluated associations between obesity and COVID-19 adverse outcomes including mortality, mechanical ventilation, intensive care unit (ICU) admission, hospitalisation, severe COVID, and COVID pneumonia. Given our interest in ascertaining the independent association between obesity and these outcomes, we selected studies that adjusted for at least one factor other than obesity. Studies were evaluated for inclusion by two independent reviewers working in duplicate.  DATA COLLECTION AND ANALYSIS: Using standardised data extraction forms, we extracted relevant information from the included studies. When appropriate, we pooled the estimates of association across studies with the use of random-effects meta-analyses. The Quality in Prognostic Studies (QUIPS) tool provided the platform for assessing the risk of bias across each included study. In our main comparison, we conducted meta-analyses for each obesity class separately. We also meta-analysed unclassified obesity and obesity as a continuous variable (5 kg/m2 increase in BMI (body mass index)). We used the GRADE framework to rate our certainty in the importance of the association observed between obesity and each outcome. As obesity is closely associated with other comorbidities, we decided to prespecify the minimum adjustment set of variables including age, sex, diabetes, hypertension, and cardiovascular disease for subgroup analysis.  MAIN RESULTS: We identified 171 studies, 149 of which were included in meta-analyses.  As compared to 'normal' BMI (18.5 to 24.9 kg/m2) or patients without obesity, those with obesity classes I (BMI 30 to 35 kg/m2), and II (BMI 35 to 40 kg/m2) were not at increased odds for mortality (Class I: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.94 to 1.16, high certainty (15 studies, 335,209 participants); Class II: OR 1.16, 95% CI 0.99 to 1.36, high certainty (11 studies, 317,925 participants)). However, those with class III obesity (BMI 40 kg/m2 and above) may be at increased odds for mortality (Class III: OR 1.67, 95% CI 1.39 to 2.00, low certainty, (19 studies, 354,967 participants)) compared to normal BMI or patients without obesity. For mechanical ventilation, we observed increasing odds with higher classes of obesity in comparison to normal BMI or patients without obesity (class I: OR 1.38, 95% CI 1.20 to 1.59, 10 studies, 187,895 participants, moderate certainty; class II: OR 1.67, 95% CI 1.42 to 1.96, 6 studies, 171,149 participants, high certainty; class III: OR 2.17, 95% CI 1.59 to 2.97, 12 studies, 174,520 participants, high certainty). However, we did not observe a dose-response relationship across increasing obesity classifications for ICU admission and hospitalisation. AUTHORS' CONCLUSIONS: Our findings suggest that obesity is an important independent prognostic factor in the setting of COVID-19. Consideration of obesity may inform the optimal management and allocation of limited resources in the care of COVID-19 patients.

A systematic review and meta-analysis of efficacy, safety, and satisfaction rates of laser combination treatments vs laser monotherapy in skin rejuvenation resurfacing.

Laser therapies have been well-established in ameliorating skin-aging consequences. This systematic review aims to determine the efficacy, safety profile, and satisfaction rates of laser combination therapies on skin rejuvenation resurfacing. A systematic search was performed in four major databases up to September 2022. Skin rejuvenation studies were eligible comprising at least one laser combination arm, inclusive of all laser types (ablative or non-ablatives), and one monotherapy arm selected from one of the combined modalities. Studies combining one laser modality with radiofrequency (RF) or intense pulse light (IPL) were also assessed. Trials that did not encompass a monotherapy control arm were evaluated independently as single-arm studies. Eighteen clinical trials recruiting 448 cases were included after screening. A total of 532 nm KTP + 1064 nm Nd:YAG and 2940 nm Er:YAG + Nd:YAG were the two most utilized laser combinations and exerted higher improvements and milder adverse events, compared to their monotherapy in most studies. Combining CO2 with rhodamine-IPL or gallium arsenide laser increased efficacy and satisfaction and brings about faster skin recovery time. Augmenting CO2 + RF did not increase improvement vs CO2 laser alone but prolonged skin erythema. Our meta-analysis revealed the pooled prevalence of quartile improvement rates as 0%, 28%, 40%, 27% in laser combination group, and 0%, 9%, 31%, 17% in laser monotherapy group, respectively. The satisfaction within each quartile category was 39%, 25%, 15%, 7% in laser combination and 20%, 25%, 16%, 17% in laser monotherapy, respectively, suggestive of the higher efficacy and satisfaction of laser combination group. The pain scores were lower in laser combination group than monotherapy (4.8 ± 1.18 vs 7.18 ± 0.7, converted on a scale of 0 to 10). Post-laser skin erythema lasted less longer in the combination group (12.8 vs 15.24 days). Laser combination therapies were discovered to be superior to their monotherapies in terms of clinical improvement rates, diminished adverse events such as pain and erythema and patients satisfaction rates. Due to paucity of high-quality reportings, additional trials are warranted to corroborate these results.

Psychometric evaluation of Persian version of Seizure Severity Questionnaire.

BACKGROUND AND PURPOSE: Seizure severity has been increasingly gaining attention as a complementary assessment to seizure frequency for the measurement of treatment responses. This study aimed to assess the reliability and external validity and of the Persian version of the Seizure Severity Questionnaire (SSQ). METHODS: The study sample was recruited from 126 patients with epilepsy who attended the neurology outpatient clinic at Imam Khomeini and Roozbeh hospitals, Tehran, Iran. The Forward-Backward technique was applied to translate the questionnaire. The reliability of SSQ was assessed by Cronbach's alpha coefficient. The external validity of SSQ was assessed by correlating SSQ scores with Quality of Life in Epilepsy Inventory-31 (QOLIE-31) subscales. RESULTS: The sample comprised 63 women (50%) and 63 men (50%) aged 13-76 years. The mean scores of SSQ items ranged from 3.46 to 5.48. Distribution was skewed for all component scores, with a tendency for the item scores to concentrate toward the highest scores. Reliability for almost all domains were moderate to good, with Cronbach's alpha ranging from 0.615 to 0.770. Component B to D and total score of SSQ had weak-to-moderate inverse correlation with QOLIE-31 subscale scores. However, the result showed no significant correlation with age, sex, or education. CONCLUSION: With some limitations, the Persian version of the SSQ shows relatively good reliability and content validity, supporting its use as a specific measure of seizure severity in epilepsy in Iran.

A systematic review of the efficacy and safety of topical cyclosporine in dermatology.

Cyclosporine-A (Cyc-A) was initially prescribed as systemic therapy for patients receiving solid organ transplants or in patients with graft versus host disease (GVHD). Topical Cyc-A is an ideal form of cyclosporine in the treatment of mucocutaneous disorders as it causes fewer systemic side effects and has more stable results than steroids; however, poor absorption through the skin makes the development of new formulations necessary to improve skin permeability. The aim of this study was to evaluate the efficacy and safety of topical Cyc-A in different dermatological conditions. A thorough systematic review was performed on PubMed/Medline, Embase, Scopus, and Web of Science databases as well as Google Scholar, and relevant studies from 2000 until January 3, 2022, were selected. The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). Topical Cyc-A was observed to be an effective medication in the treatment of oral lichen planus, psoriasis, burning mouth syndrome, Pyoderma Gangrenosum, and Zoon's balanitis. Adverse side effects such as dysphagia, burning sensation, lips swelling, and gastrointestinal upset were reported following Cyc-A mouthwash use, whereas mild erythema, dryness, and fissuring of the skin were observed following the Cyc-A lipogel application. Topical Cyc-A was found to be a good alternative to traditional treatment regimens for immune-mediated mucocutaneous conditions. Cyc-A can be considered as a safe and efficient option in cases of long-term treatment as it does not have the same adverse effects of long-term steroids.

A systematic review on mucocutaneous presentations after COVID-19 vaccination and expert recommendations about vaccination of important immune-mediated dermatologic disorders.

With dermatologic side effects being fairly prevalent following vaccination against COVID-19, and the multitude of studies aiming to report and analyze these adverse events, the need for an extensive investigation on previous studies seemed urgent, in order to provide a thorough body of information about these post-COVID-19 immunization mucocutaneous reactions. To achieve this goal, a comprehensive electronic search was performed through the international databases including Medline (PubMed), Scopus, Cochrane, Web of science, and Google scholar on July 12, 2021, and all articles regarding mucocutaneous manifestations and considerations after COVID-19 vaccine administration were retrieved using the following keywords: COVID-19 vaccine, dermatology considerations and mucocutaneous manifestations. A total of 917 records were retrieved and a final number of 180 articles were included in data extraction. Mild, moderate, severe and potentially life-threatening adverse events have been reported following immunization with COVID vaccines, through case reports, case series, observational studies, randomized clinical trials, and further recommendations and consensus position papers regarding vaccination. In this systematic review, we categorized these results in detail into five elaborate tables, making what we believe to be an extensively informative, unprecedented set of data on this topic. Based on our findings, in the viewpoint of the pros and cons of vaccination, mucocutaneous adverse events were mostly non-significant, self-limiting reactions, and for the more uncommon moderate to severe reactions, guidelines and consensus position papers could be of great importance to provide those at higher risks and those with specific worries of flare-ups or inefficient immunization, with sufficient recommendations to safely schedule their vaccine doses, or avoid vaccination if they have the discussed contra-indications.

Systematic review and meta-analysis of randomized clinical trials comparing efficacy, safety, and satisfaction between ablative and non-ablative lasers in facial and hand rejuvenation/resurfacing.

Skin aging inevitably begins from the very early days of life. The lasers used in skin rejuvenation are mainly of two types: ablative and non-ablative. This meta-analysis aimed at comparing ablative with non-ablative lasers in terms of their efficacy and safety in skin rejuvenation. Articles published by March 15, 2020 in Embase, Medline (PubMed), Scopus, Cochrane, and clinicalTrials.gov were searched. The inclusion criteria included randomized controlled clinical trials (RCTs) in English using ablative and non-ablative lasers and comparing their safety and efficiency in wrinkle improvement and photoaging therapy. Out of 1353 extracted articles, 11 were selected for qualitative synthesis and of these, 4 were quantitatively analyzed. Different modes of various lasers were implemented; the ablative lasers included Erbium: yttrium-aluminium-garnet (Er:YAG) and CO2, besides the non-ablative lasers, comprised Ytterbium/Erbium, Erbium: Glass, neodymium: yttrium-aluminum-garnet (Nd:YAG), and alexandrite. Pooled analyses on 124 participants showed insignificant differences between ablative and non-ablative lasers in the likelihood of excellent improvement with an odds ratio of 0.83 (95% CI: 0.24, 2.83). The analyses also showed good improvement with an odds ratio of 0.88 (95% CI: 0.44, 1.78), fair improvement with an odds ratio of 1.13 (95% CI: 0.56, 2.26) and side effects with an odds ratio of 0.82 (95% CI: 0.43, 1.56). The efficacy and safety of ablative laser were not higher than those of non-ablative laser in skin rejuvenation. Given the small samples of the included articles, it is recommended that further high-quality RCTs be conducted using larger samples to confirm this conclusion.

A systematic review of the histopathologic survey on skin biopsies in patients with Corona Virus Disease 2019 (COVID-19) who developed virus or drug-related mucocutaneous manifestations.

The mucocutaneous manifestations of Corona Virus Disease 2019 (COVID-19) logically may reflect systemic visceral involvements. These findings are visible and easy to approach like biopsies for exact histopathologic evaluations. This systematic review was conducted to collect the mucocutaneous histopathologic data of COVID-19 patients for future investigations and interpretations. The COVID-19 dermatology resource of the Centre of Evidence-Based Dermatology (CEBD) at the University of Nottingham, PubMed, Scopus, Google Scholar and Medscape was searched for relevant English articles published by June 3, 2020. This review included 31 articles, involving 459 patients. The common primary virus-related mucocutaneous manifestations are easy to approach in the course of COVID-19. The authors of this study supposed dermatopathological findings as the predictors of the nature of potential systemic involvements and outcomes of COVID-19. Scrutinizing these findings can help with adopting more effective therapeutic and management strategies; nevertheless, this review found the severity and time of onset of symptoms not to be associated with the laboratory and histopathological findings. Deterioration of clinical conditions and laboratory tests was also not related to the histopathological findings. It is recommended that meta-analyses be conducted in the future to detail on these data for having more comprehensive and better conclusion.

Rare clinical features of the Ellis van Creveld syndrome: A case report and literature review.

Ellis van Creveld syndrome (EVC) is a rare autosomal recessive disorder also called chondroectodermal dysplasia. This study reports on a 40-year-old woman from Iran with a syndromic appearance consisting of a coarse face, conical anterior teeth, dental agenesis and permanent teeth at birth, several small extralabial, nonmidline frenula with a high-arched palate, and a large maxillary labial frenulum. The patient had cyanosis on her lips since childhood and a history of adenoid tonsillectomy surgery. She also had androgenic alopecia, an elongated trunk with excessive lordosis and pectus excavatum, polycystic ovarian syndrome, and a history of two periods in a month. She also had multiple fibrocystic cysts in her breasts, lower extremity deformity, dysplastic genu valgum, and short limb dwarfism; she had undergone left knee surgery four times and had severe osteoporosis in some of her bones and some hyperpigmented patches on the dorsal of the left hand. Her hands and feet were also wide and markedly deformed with hypoplastic fingernails and toenails, and she had bimanual hexadactyly on the ulnar side of the hands. She also had a history of severe hypotension and cyanosis during surgery and suffered from congenital heart failure and had undergone open heart surgery for correcting her atrial heart defect. In this study pectus excavatum, Phrygian cap gallbladder, liver hemangioma, polycystic ovarian disease, and breast fibrocystic cysts was reported for first time in this case of EVC syndrome. This case was reported and all articles regarding common, uncommon, rare, and extremely rare presentations of this syndrome were reviewed.

The role of topical timolol in wound healing and the treatment of vascular lesions: A narrative review.

Beta-2 adrenergic receptors are the only subgroup of beta-adrenergic receptors expressed in the membrane of large cells, including skin keratinocytes, fibroblasts, and melanocytes. Alterations in the function or concentration of ß2 adrenoreceptors related to keratinocytes are associated with some skin conditions. Some findings suggest the role of ß2 adrenoreceptors in maintaining the function and integrity of the epidermis. Beta-receptor antagonists can be systemically and topically effective in healing hemangioma, paronychia, vasculitis ulcer, tufted angioma, acute and chronic wounds. Most studies with a strong design on this subject deal with the systemic form, but recently, numerous case and group reports and smaller studies have focused on topical forms, especially topical timolol. The present comprehensive review study surveys the role of topical timolol in acute and chronic wound healing in the field of dermatology.

A systematic review on treatment-related mucocutaneous reactions in COVID-19 patients.

Most of drugs could have certain mucocutaneous reactions and COVID-19 drugs are not an exception that we focused. We systematically reviewed databases until August 15, 2020 and among initial 851 articles, 30 articles entered this study (20 case reports, 4 cohorts, and 6 controlled clinical trials). The types of reactions included AGEP, morbiliform drug eruptions, vasculitis, DRESS syndrome, urticarial vasculitis, and so on. The treatments have been used before side effects occur, included: antimalarial, anti-viral, antibiotics, tocilizumab, enoxaparin and and so on. In pandemic, we found 0.004% to 4.15% of definite drug-induced mucocutaneous reactions. The interval between drug usage and the eruption varied about few hours to 1 month; tightly dependent to the type of drug and hydroxychloroqine seems to be the drug with highest mean interval. Antivirals, antimalarials, azithromycin, and tocilizumab are most responsive drugs for adverse drug reactions, but antivirals especially in combination with antimalarial drugs are in the first step. Types of skin reactions are usually morbilliform/exanthematous maculopapular rashes or urticarial eruptions, which mostly may manage by steroids during few days. In the setting of HCQ, specific reactions like AGEP should be considered. Lopinavir/ritonavir is the most prevalent used drug among antivirals with the highest skin adverse reaction; ribarivin and remdisivir also could induce cutaneous drug reactions but favipiravir has no or less adverse effects. Logically the rate of dermatologic adverse effects among anivirals may relate to their frequency of usage. Rarely, potentially life-threatening reactions may occur. Better management strategies could achieve by knowing more about drug-induced mucocutaneous presentations of COVID-19.

Therapeutic options and hot topics in vitiligo with special focus on pediatrics' vitiligo: A comprehensive review study.

Vitiligo is a common skin disorder with an estimated worldwide prevalence to 2.28% which is connected with selective melanocytes loss which leads to depigmentation and chalky-white macules. Vitiligo may be dismissed as a cosmetic problem and may have psychologic impacts on patients. It is occurring in both children and adults and is considered as the most common depigmenting skin disorder in the world. There are still many unknown topics about this disease regarding to its treatment in pediatrics, curable drugs and manifestations. Therefore, we decided to evaluate the recent studies about its therapeutic strategies in pediatrics. Topical therapies should be considered as first line treatment in children, but phototherapy especially NBUVB may be used after topical treatment modalities failure or in extensive or rapidly progressive disease. Our suggestion for the treatment of this disease in children is to use combine treatment modalities with observing safety according to the patient's age.

Severe and life-threatening COVID-19-related mucocutaneous eruptions: A systematic review.

OBJECTIVES: Earlier diagnosis and the best management of virus-related, drug-related or mixed severe potentially life-threatening mucocutaneous reactions of COVID-19 patients are of great concern. These patients, especially hospitalised cases, are usually in a complicated situation (because of multi-organ failures), which makes their management more challenging. In such consultant cases, achieving by the definite beneficial management strategies that therapeutically address all concurrent comorbidities are really hard to reach or even frequently impossible. METHODS: According to the lack of any relevant systematic review, we thoroughly searched the databases until 5 October 2020 and finally found 57 articles including 93 patients. It is needed to know clinical presentations of these severe skin eruptions, signs and symptoms of COVID in these patients, time of skin rash appearance, classifying drug-related or virus-related skin lesions, classifying the type of skin rash, patients' outcome and concurrent both COVID-19 therapy and skin rash treatment. RESULT: Severe and potential life-threatening mucocutaneous dermatologic manifestations of COVID-19 usually may be divided into three major categories: virus-associated, drug-associated, and those with uncertainty about the exact origin. Angioedema, vascular lesions, toxic shock syndrome, erythroderma, DRESS, haemorrhagic bulla, AGEP, EM, SJS and TEN, generalised pustular figurate erythema were the main entities found as severe dermatologic reactions in all categories. CONCLUSION: We can conclude vascular injuries may be the most common cause of severe dermatologic manifestations of COVID-19, which is concordant with many proposed hypercoagulation tendencies and systemic inflammatory response syndrome as one of the most important pathomechanisms of COVID-19 so the skin may show these features in various presentations and degrees.

A systematic review on efficacy, safety, and treatment-durability of low-dose rituximab for the treatment of Pemphigus: special focus on COVID-19 pandemic concerns.

BACKGROUND: Rituximab is a FDA-approved monoclonal antibody for adults with moderate to severe potentially life-threatening pemphigus vulgaris. Recent studies have focused on assessments of efficacy and safety of low-dose rituximab (<2 gram in each cycle). METHOD: Databases were searched from 2010 to 2020 (last update: 1 June 2020). RESULT: Nine studies were entered; including180 cases (92: women, 88: men, age range: 9-83 years). The dosages of each Rituximab cycle varied between ultra-low-dose (≤500 mg for a cycle, either multiple infusions or a single infusion), low-dose (2 × 375 mg/m2 or 2 × 500 mg) and modified-dose (3 × 375 mg/m2 or 3 × 500 mg). The efficacy and safety of Rituximab in the studies are known by the recovery time, relapse time, and side events. According to the studies, 2 × 500 can lead to complete remission in a broad range, from 35 to 82%. These differences might be explained by different end-points and variable cumulative corticosteroid dosage after RTX administration. Although the studies showed that low dose RTX is efficient, there are some controversies regarding the choosing low-dose for severe patients. CONCLUSION: Considering the effectiveness of low-dose, intermediate dose, and ultra-low-dose protocols of Rituximab in inducing remission in pemphigus disease and considering factors such as cost of therapy, and the need to induce a minimum of immunosuppression for a minimum duration in the COVID-19 pandemic, suggested to use low-dose Rituximab protocol (2 infusions of 500 mg Rituximab: interval of 2 weeks) to induce the remission in mild-to-moderate pemphigus patients.

Cutaneous manifestations and considerations in COVID-19 pandemic: A systematic review.

COVID-19 had a great impact on medical approaches among dermatologist. This systematic review focuses on all skin problems related to COVID-19, including primary and secondary COVID-related cutaneous presentations and the experts recommendations about dermatological managements especially immunomodulators usage issues. Search was performed on PubMed, Scopus, Embase and ScienceDirect. Other additional resources were searched included Cochrane, WHO, Medscape and coronavirus dermatology resource of Nottingham university. The search completed on May 3, 2020. Three hundred seventy-seven articles assigned to the inclusion and exclusion groups. Eighty-nine articles entered the review. Primary mucocutaneous and appendageal presentations could be the initial or evolving signs of COVID-19. It could be manifest most commonly as a maculopapular exanthamatous or morbiliform eruption, generalized urticaria or pseudo chilblains recognized as "COVID toes" (pernio-like acral lesions or vasculopathic rashes). During pandemic, Non-infected non-at risk patients with immune-medicated dermatologic disorders under treatment with immunosuppressive immunomodulators do not need to alter their regimen or discontinue their therapies. At-risk o suspected patients may need dose reduction, interval increase or temporary drug discontinuation (at least 2 weeks). Patients with an active COVID-19 infection should hold the biologic or non-biologic immunosuppressives until the complete recovery occur (at least 4 weeks).

Treatment of COVID-19 with pentoxifylline: Could it be a potential adjuvant therapy?

The world is facing a viral pandemic of a new coronavirus called COVID-19. Pentoxifylline is a methyl-xanthine derivative and it inhibits the phosphodiesterase IV (PDE IV). This drug is known for its unique features as an immunomodulatory and anti-inflammatory agent, also it could have antiviral affects. This is a scoping review, in which all related articles on COVID-19 and the probable benefits of Pentoxifylline against COVID-19 pathogenesis, in Medline, Scopus, Web of Sciences, and Google Scholar up to 20 March 2020 with proper keywords including: pentoxifylline, Pentoxil, COVID-19, coronavirus, treatment, anti-inflammatory, immunomodulatory, antifibrosis, oxygenation, circulation, bronchodilator, ARDS, and organ failure. We found many confirmatory data on proper efficacy of pentoxifylline on controlling COVID-19 and its consequences. The antiviral, anti-inflammatory, anti-oxidative, immune-modulatory, bronchodilator and respiratory supportive effects and protective roles in organ failures of PTX, along with its main functions means better circulation-oxygenation properties, low price and safety, make it a promising drug to be considered for COVID-19 treatment, especially as an adjuvant therapy in combination with other drugs.

N-acetylcysteine and coronavirus disease 2019: May it work as a beneficial preventive and adjuvant therapy? A comprehensive review study.

BACKGROUND: Coronaviruses are major pathogens of respiratory system causing different disorders, including the common cold, Middle East respiratory syndrome, and severe acute respiratory syndrome. Today's global pandemic coronavirus disease 2019 (COVID-19) has high mortality rate, with an approximate of 20% in some studies, and is 30-60 times more fatal than the common annual influenza, However, there is still no gold standard treatment for it. N-acetylcysteine (NAC) is a well-known multi-potential drug with hypothetically probable acceptable effect on COVID-related consequences, which we completely focused in this comprehensive review. MATERIALS AND METHODS: PubMed, Scopus, Science Direct, and Google Scholar have been searched. Study eligibility criteria: efficacy of NAC in various subclasses of pathogenic events which may occur during COVID-19 infection. Efficacy of NAC for managing inflammatory or any symptoms similar to symptoms of COVID-19 was reviewed and symptom improvements were assessed. RESULTS: Randomized clinical trials introduced NAC as an antioxidant glutathione analog and detoxifying agent promoted for different medical conditions and pulmonary disorders to alleviate influenza and reduce mortality by 50% in influenza-infected animals. The beneficial effects of NAC on viral disorders, including Epstein-Barr virus, HIV and hepatitis, and well-known vital organ damages were also exist and reported. CONCLUSION: We classified the probable effects of NAC as oxidative-regulatory and apoptotic-regulatory roles, antiviral activities, anti-inflammatory roles, preventive and therapeutic roles in lung disorders and better oxygenation functions, supportive roles in intensive care unit admitted patients and in sepsis, positive role in other comorbidities and nonpulmonary end-organ damages or failures and even in primary COVID-associated cutaneous manifestations. Based on different beneficial effects of NAC, it could be administered as a potential adjuvant therapy for COVID-19 considering patient status, contraindications, and possible drug-related adverse events.

Melatonin: Current evidence on protective and therapeutic roles in gynecological diseases.

Melatonin, a potent antioxidant and free radical scavenger, has been demonstrated to be effective in gynecological conditions and female reproductive cancers. This review consolidates the accumulating evidence on melatonin's multifaceted protective effects in different pathological contexts. In gynecological conditions such as endometriosis, polycystic ovary syndrome (PCOS), and uterine leiomyoma, melatonin has shown promising effects in reducing oxidative stress, inflammation, and hormonal imbalances. It inhibits adhesion molecules' production, and potentially mitigates leukocyte adherence and inflammatory responses. Melatonin's regulatory effects on hormone production and insulin sensitivity in PCOS individuals make it a promising candidate for improving oocyte quality and menstrual irregularities. Moreover, melatonin exhibits significant antitumor effects by modulating various signaling pathways, promoting apoptosis, and suppressing metastasis in breast cancers and gynecological cancers, including ovarian, endometrial, and cervical cancers. Furthermore, melatonin's protective effects are suggested to be mediated by interactions with its receptors, estrogen receptors and other nuclear receptors. The regulation of clock-related genes and circadian clock systems may also contribute to its inhibitory effects on cancer cell growth. However, more comprehensive research is warranted to fully elucidate the underlying molecular mechanisms and establish melatonin as a potential therapeutic agent for these conditions.

Evaluation of efficacy and safety of vitiligo treatment with micro-needling combined with N-Acetylcysteine and micro-needling alone: A double-blinded randomized controlled clinical trial.

INTRODUCTION: Vitiligo is a skin pigmentation disorder caused by the selective degradation of melanocytes. This study investigates the therapeutic effects of microneedling with and without N-acetylcysteine (NAC) in patients with persistent and limited vitiligo. METHOD: This research employed a clinical trial design with double-blind randomization. Individuals affected by vitiligo and seeking treatment at Rasool Akram Medical Complex were divided into two separate treatment groups. In the intervention group, 24 affected areas underwent meso-microneedling using 5% NAC ampoules over six sessions, in addition to the application of 4.7% NAC cream once daily on the specified area. Conversely, the control group, consisting of 22 lesions, underwent microneedling using distilled water during six sessions. The severity of lesions and the extent of repigmentation were gauged using the Modified VETI Score. Assessment of treatment efficacy was determined through both physician evaluations and patient feedback. RESULTS: Twenty patients with a mean age of 36.4 years were recruited. The mean percentage of lesions and their intensity were significantly improved 2 weeks after the third session and 1 month after the end of the treatment (p < 0.01). There was no statistically significant difference between the intervention and control groups. Gender, age, family history, duration of disease, duration of disease stability, and history of hypothyroidism had no statistically significant relationship with patients' treatment outcomes (p > 0.05). CONCLUSION: Microneedling with or without the application of NAC appears to be an effective treatment option for persistent vitiligo lesions. However, despite the higher improvement rate with the application of NAC, the difference was not significant.

A systematic review and meta-analysis of investigating the mutual impact of COVID-19 and psoriasis: Focusing on COVID-19 course in psoriasis and the opinion on biologics in this setting.

INTRODUCTION: This systematic review and meta-analysis aims to investigate the mutual impact of COVID-19 and psoriasis to inform clinical practice and future research. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis protocol for systematic reviews and searched PubMed, Web of Science, Scopus, and Google Scholar until May 1, 2022. Eligibility criteria included full-text articles in English reporting COVID-19 treatment outcomes in psoriasis patients. Studies on animals, letters to editors, non-English studies, and studies with no access to full articles were excluded. Search results were screened and data were extracted by two groups of reviewers with any discrepancies resolved by the senior author. The risk of bias was assessed using ROBINS-I for nonrandomized studies. The hospitalization rate, Intensive Care Unit (ICU) admission rate, case fatality rate, odds ratios of COVID-19 infection and hospitalization rate in psoriasis patients were extracted and analyzed using random effects analysis to calculate pooled prevalence and odds ratios, as well as to explore heterogeneity. RESULTS: We found 1980 records from four databases and included 20 studies after screening and removing duplicates. These studies evaluated 185,000 psoriasis patients and included eight retrospective cohort studies, one case-control study, three cross-sectional studies, and eight case series studies. The impact of the COVID-19 pandemic on psoriasis treatment and the outcome of COVID-19 infection in psoriasis patients receiving different forms of treatment were evaluated. The pooled data from included studies showed that the incidence rate of COVID-19 infection among psoriasis patients was 0.03% (confidence interval [CI]: 0.01-0.06), with a pooled odds ratio of 1.97 (CI: 0.69-5.60) compared to the general population. The hospitalization rate, ICU admission rate, and case fatality rate for psoriasis patients with COVID-19 were 0.17 (CI: 0.10-0.31), 0.06 (CI: 0.06-0.46), and 0.02 (CI: 0.01-0.04), respectively. Additionally, psoriasis patients receiving systemic nonbiologic therapy had a pooled odds ratio of 2.32 (CI: 1.18-4.57) for hospitalization compared to those using biologic agents. CONCLUSION: Studies have shown that biologic therapy for psoriasis did not increase the risk of hospitalization due to COVID-19 infection and may have even offered some protection. Treatment adherence was higher in psoriasis patients receiving biologic therapies than those receiving conventional therapies. These findings suggest that psoriasis treatment did not negatively impact COVID-19 infection and that treatment could be continued on a case-by-case basis during the pandemic.