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Indian Dermatology Online Journal 2023Melasma is an acquired disorder, which presents with well-demarcated, brown-colored hyperpigmented macules, commonly involving the sun-exposed areas such as the face. It... (Review)
Review
INTRODUCTION
Melasma is an acquired disorder, which presents with well-demarcated, brown-colored hyperpigmented macules, commonly involving the sun-exposed areas such as the face. It is a chronic and distressing condition, affecting the patients' quality of life, and has been conventionally treated with "first-line" agents including hydroquinone (HQ) alone or as a part of a triple combination cream (TCC), while "second-line" options include chemical peels, and third line options include laser therapy.
MATERIALS AND METHODS
A systematic search was performed for all topical and systemic treatments for melasma up till May 4, 2021, using the PubMed and EMBASE databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The search terms "melasma" and "treatment" were used to search for the relevant articles on both these databases, and a total of 4020 articles were identified. After removing the duplicate entries and screening the titles, abstracts, and full-text articles, we identified 174 randomized controlled trials (RCTs) or controlled clinical trials.
RESULTS
Based on our review, HQ, TCCs, sunscreens, kojic acid (KA), and azelaic acid receive grade A recommendation. Further large-scale studies are required to clearly establish the efficacy of topical vitamin C, resorcinol, and topical tranexamic acid (TXA). Several newer topical agents may play a role only as an add-on or second-line drugs or as maintenance therapy. Oral TXA has a strong recommendation, provided there are no contraindications. Procyanidins, Polypodium leucotomos (PL), and even synbiotics may be taken as adjuncts.
DISCUSSION
Several newer topical and systemic agents with multimodal mechanisms of action have now become available, and the balance seems to be tipping in favor of these innovative modalities. However, it is worth mentioning that the choice of agent should be individualized and subject to availability in a particular country.
PubMed: 38099013
DOI: 10.4103/idoj.idoj_490_22 -
American Journal of Obstetrics &... Aug 2023Tranexamic acid is a cost-effective intervention for the prevention of postpartum hemorrhage among women who undergo cesarean delivery, but the evidence to support its... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Tranexamic acid is a cost-effective intervention for the prevention of postpartum hemorrhage among women who undergo cesarean delivery, but the evidence to support its use is conflicting. We conducted this meta-analysis to evaluate the efficacy and safety of tranexamic acid in low- and high-risk cesarean deliveries.
DATA SOURCES
We searched MEDLINE (via PubMed), Embase, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform portal from inception to April 2022 (updated October 2022 and February 2023) with no language restrictions. In addition, grey literature sources were also explored.
STUDY ELIGIBILITY CRITERIA
All randomized controlled trials that investigated the prophylactic use of intravenous tranexamic acid in addition to standard uterotonic agents among women who underwent cesarean deliveries in comparison with a placebo, standard treatment, or prostaglandins were included in this meta-analysis.
METHODS
We used the revised Cochrane Risk of Bias tool (RoB 2.0) to assess the quality of the included randomized controlled trials. RevMan 5.4 was used to conduct all statistical analyses using a random-effects model.
RESULTS
We included 50 randomized controlled trials (6 in only high-risk patients and 2 with prostaglandins as the comparator) that evaluated tranexamic acid in our meta-analysis. Tranexamic acid reduced the risk for blood loss >1000 mL, the mean total blood loss, and the need for blood transfusion in both low- and high-risk patients. Tranexamic acid was associated with a beneficial effect in the secondary outcomes, including a decline in hemoglobin levels and the need for additional uterotonic agents. Tranexamic acid increased the risk for nonthromboembolic adverse events but, based on limited data, did not increase the incidence of thromboembolic events. The administration of tranexamic acid before skin incision, but not after cord clamping, was associated with a large benefit. The quality of evidence was rated as low to very low for outcomes in the low-risk population and moderate for most outcomes in the high-risk subgroup.
CONCLUSION
Tranexamic acid may reduce the risk for blood loss in cesarean deliveries with a higher benefit observed in high-risk patients, but the lack of high-quality evidence precludes any strong conclusions. The administration of tranexamic acid before skin incision, but not after cord clamping, was associated with a large benefit. Additional studies, especially in the high-risk population and focused on evaluating the timing of tranexamic acid administration, are needed to confirm or refute these findings.
Topics: Humans; Female; Pregnancy; Tranexamic Acid; Blood Loss, Surgical; Cesarean Section; Randomized Controlled Trials as Topic; Postpartum Hemorrhage; Antifibrinolytic Agents; Prostaglandins
PubMed: 37311484
DOI: 10.1016/j.ajogmf.2023.101049 -
Drugs Nov 2023Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on... (Review)
Review
Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on managing abnormal uterine bleeding (AUB) and dysmenorrhea, the main symptoms of adenomyosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid provide limited support for mild symptoms or symptom re-exacerbation during hormone therapy. The levonorgestrel-releasing intrauterine system (LNG-IUS) is commonly employed in adenomyosis management, showing promise in symptom improvement and reducing uterine size, despite the lack of standardized guidelines. Dienogest (DNG) also exhibits potential benefits, but limited evidence hinders treatment recommendations. Danazol, while effective, is limited by androgenic side effects. Combined oral contraceptives (COCs) may be less effective than progestins but can be considered for contraception in young patients. Gonadotropin-releasing hormone (GnRH) agonists effectively manage symptoms but induce menopausal symptoms with prolonged use. GnRH antagonists are a recent option requiring further investigation. Aromatase inhibitors (AIs) show promise in alleviating AUB and pelvic pain, but their safety necessitates exploration and limited use within trials for refractory patients. This review highlights the complexity of diagnosing adenomyosis, its coexistence with endometriosis and uterine leiomyomas, and its impact on fertility and quality of life, complicating treatment decisions. It emphasizes the need for research on guidelines for medical management, fertility outcomes, long-term effects of therapies, and exploration of new investigational targets. Future research should optimize therapeutic strategies, expand our understanding of adenomyosis and its management, and establish evidence-based guidelines to improve patient outcomes and quality of life.
Topics: Female; Humans; Adenomyosis; Quality of Life; Uterus; Progestins; Gonadotropin-Releasing Hormone; Levonorgestrel
PubMed: 37837497
DOI: 10.1007/s40265-023-01957-7 -
Journal of Thrombosis and Haemostasis :... Dec 2023Fibrinolysis is the system primarily responsible for removal of fibrin deposits and blood clots in the vasculature. The terminal enzyme in the pathway, plasmin, is... (Review)
Review
Fibrinolysis is the system primarily responsible for removal of fibrin deposits and blood clots in the vasculature. The terminal enzyme in the pathway, plasmin, is formed from its circulating precursor, plasminogen. Fibrin is by far the most legendary substrate, but plasmin is notoriously prolific and is known to cleave many other proteins and participate in the activation of other proteolytic systems. Fibrinolysis is often overshadowed by the coagulation system and viewed as a simplistic poorer relation. However, the primordial plasminogen activators evolved alongside the complement system, approximately 70 million years before coagulation saw the light of day. It is highly likely that the plasminogen activation system evolved with its roots in primordial immunity. Almost all immune cells harbor at least one of a dozen plasminogen receptors that allow plasmin formation on the cell surface that in turn modulates immune cell behavior. Similarly, numerous pathogens express their own plasminogen activators or contain surface proteins that provide binding sites for host plasminogen. The fibrinolytic system has been harnessed for clinical medicine for many decades with the development of thrombolytic drugs and antifibrinolytic agents. Our refined understanding and appreciation of the fibrinolytic system and its alliance with infection and immunity and beyond are paving the way for new developments and interest in novel therapeutics and applications. One must ponder as to whether the nomenclature of the system hampered our understanding, by focusing on fibrin, rather than the complex myriad of interactions and substrates of the plasminogen activation system.
Topics: Humans; Fibrinolysis; Fibrinolysin; Plasminogen Activators; Plasminogen; Fibrin; Serine Proteases
PubMed: 38000850
DOI: 10.1016/j.jtha.2023.09.012 -
Stroke Sep 2023Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid... (Randomized Controlled Trial)
Randomized Controlled Trial
Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.
BACKGROUND
Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH.
METHODS
We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis.
RESULTS
Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; =0.40). There was a signal for interaction with onset-to-treatment time (=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; =0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; =0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation.
CONCLUSIONS
In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH.
REGISTRATION
URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.
Topics: Humans; Female; Aged, 80 and over; Male; Tranexamic Acid; Anticoagulants; Administration, Oral; Cerebral Hemorrhage; Antifibrinolytic Agents; Hemostatics; Hematoma; Thromboembolism
PubMed: 37466000
DOI: 10.1161/STROKEAHA.123.042866 -
Acta Clinica Croatica Aug 2023Tranexamic acid is a synthetic derivative of the amino acid lysine, an antifibrinolytic that is primarily used to reduce bleeding in surgery, trauma, and dental... (Review)
Review
Tranexamic acid is a synthetic derivative of the amino acid lysine, an antifibrinolytic that is primarily used to reduce bleeding in surgery, trauma, and dental procedures. Its anti-inflammatory and anti-angiogenic properties, as well as its ability to suppress melanogenesis have enabled it to be used in dermatology in the treatment of skin conditions such as melasma, acne, post-inflammatory hyperpigmentation, rosacea and angioedema. Tranexamic acid can be used by various routes of administration including oral, topical and intradermal injection, and in combination with other treatment methods. This review article presents evidence for the effectiveness of tranexamic acid in the treatment of various skin disorders.
Topics: Humans; Tranexamic Acid; Dermatology; Antifibrinolytic Agents; Hemorrhage; Melanosis; Skin Diseases; Treatment Outcome
PubMed: 38549597
DOI: 10.20471/acc.2023.62.02.16 -
Biomedicine & Pharmacotherapy =... Oct 2023The chronic disease psoriasis is associated with severe inflammation and abnormal keratinocyte propagation in the skin. Tranexamic acid (TXA), a plasmin inhibitor, is...
The chronic disease psoriasis is associated with severe inflammation and abnormal keratinocyte propagation in the skin. Tranexamic acid (TXA), a plasmin inhibitor, is used to cure serious bleeding. We investigated whether TXA ointment mitigated Imiquimod (IMQ)-induced psoriasis-like inflammation. Furthermore, this study investigated the effect of noncytotoxic concentrations of TXA on IL-17-induced human keratinocyte (HaCaT) cells to determine the status of proliferative psoriatic keratinocytes. We found that TXA reduced IMQ-induced psoriasis-like erythema, thickness, scaling, and cumulative scores (erythema plus thickness plus scaling) on the back skin of BALB/c mice. Additionally, TXA decreased ear thickness and suppressed hyperkeratosis, hyperplasia, and inflammation of the ear epidermis in IMQ-induced BALB/c mice. Furthermore, TXA inhibited IMQ-induced splenomegaly in BALB/c mouse models. In IL-17-induced HaCaT cells, TXA inhibited ROS production and IL-8 secretion. Interestingly, TXA suppressed the IL-17-induced NFκB signaling pathway via IKK-mediated IκB degradation. TXA inhibited IL-17-induced activation of the NLRP3 inflammasome through caspase-1 and IL1β expression. TXA inhibited IL-17-induced NLRP3 inflammasome activation by enhancing autophagy, as indicated by LC3-II accumulation, p62/SQSTM1 expression, ATG4B inhibition, and Beclin-1/Bcl-2 dysregulation. Notably, TXA suppressed IL-17-induced Nrf2-mediated keratin 17 expression. N-acetylcysteine pretreatment reversed the effects of TXA on NFκB, NLRP3 inflammasomes, and the Nrf2-mediated keratin 17 pathway in IL-17-induced HaCaT cells. Results further confirmed that in the ear skin of IMQ-induced mice, psoriasis biomarkers such as NLRP3, IL1β, Nrf2, and keratin 17 expression were downregulated by TXA treatment. TXA improves IMQ-induced psoriasis-like inflammation in vivo and psoriatic keratinocytes in vitro. Tranexamic acid is a promising future treatment for psoriasis.
Topics: Humans; Animals; Mice; Interleukin-17; Tranexamic Acid; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Keratin-17; NF-E2-Related Factor 2; Psoriasis; Dermatitis; Skin; Keratinocytes; Inflammation; Imiquimod; NF-kappa B; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37573659
DOI: 10.1016/j.biopha.2023.115307