Disease modification in chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a debilitating, inflammatory skin condition characterized by infiltrating immune cells. Available treatments are limited to improving the signs and symptoms. There is an unmet need to develop therapies that target disease-driving pathways upstream of mast cell activation to inhibit or delay the progression of CSU and associated comorbidities. Here, we aim to define disease modification due to a treatment intervention and criteria that disease-modifying treatments (DMTs) must meet in CSU. We have defined disease modification in CSU as a favorable treatment-induced change in the underlying pathophysiology and, therefore, the disease course, which is clinically beneficial and enduring. A DMT must fulfil the following criteria: (1) prevents or delays the progression of CSU, (2) induces long-term, therapy-free clinical remission, which is the sustained absence of CSU signs and symptoms without the need for treatment, and (3) affects the underlying mechanism of CSU, as demonstrated by an effect on disease-driving signals and/or a biomarker. DMTs in CSU should slow disease progression, achieve long-lasting disease remission, target disease-driving mechanisms, reduce mast cell-activating IgE autoantibodies, target cytokine profile polarization, and normalize the gut microbiome and barrier. Treating CSU at the immune system level could provide valuable alternatives to pharmacotherapy in CSU management. Specific DMTs in CSU are yet to be developed, but some show potential benefits, such as inhibitors of Bruton's Tyrosine Kinase, IL-4 and IL-13. Future therapies could prevent CSU signs and symptoms, achieve long-term clinical benefits after discontinuing treatment, and prevent associated concomitant disorders.

Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review.

Non-small-cell lung cancer (NSCLC) comprises approximately 85% of all lung cancer cases, often diagnosed at advanced stages, which diminishes the effective treatment options and survival rates. This systematic review assesses the utility of emerging biomarkers-circulating tumor DNA (ctDNA), microRNAs (miRNAs), and the blood tumor mutational burden (bTMB)-enhanced by next-generation sequencing (NGS) to improve the diagnostic accuracy, prognostic evaluation, and treatment strategies in NSCLC. Analyzing data from 37 studies involving 10,332 patients from 2020 to 2024, the review highlights how biomarkers like ctDNA and PD-L1 expression critically inform the selection of personalized therapies, particularly beneficial in the advanced stages of NSCLC. These biomarkers are critical for prognostic assessments and in dynamically adapting treatment plans, where high PD-L1 expression and specific genetic mutations (e.g., ALK fusions, EGFR mutations) significantly guide the use of targeted therapies and immunotherapies. The findings recommend integrating these biomarkers into standardized clinical pathways to maximize their potential in enhancing the treatment precision, ultimately fostering significant advancements in oncology and improving patient outcomes and quality of life. This review substantiates the prognostic and predictive value of these biomarkers and emphasizes the need for ongoing innovation in biomarker research.

Efficacy and safety of a combination anti-tumor against breast cancer in the central and south of Iraq.

OBJECTIVE: Aim: To explore efficacy and safety of combined anti-tumor treatments against breast cancer to help health professionals and decision-makers take strategies to slow the spread of breast cancer and improve women's health. PATIENTS AND METHODS: Material and Methods: A cross-sectional study was used by various Iraqi governments. The survey was conducted between July 1, 2022 and April 30, 2023. The study depended on describing studying of 100 patients in detail and with long-term follow-up who go to hospitals and take anti-cancer medications from different provinces of central and south Iraq. The questionnaire form contains 17 fields divided into three sections. The diagnosis tumor before and after treatment parameters: histopathology, CT-scan, tumor marker (Nuclear protein Ki67, Cancer antigen 153 (CA 153), human epidermal growth factor receptor 2, and carcinoembryonic antigen), renal function tests, liver function tests, and Complete Blood Count. RESULTS: Results: The use of anti-tumor medications was coupled with markedly decreased tumor cell proliferation via reduced biomarker levels of cancer (CA-15-3), HER-2, and Ki-67 levels, and decreased the mammary ductal epithelium's thickness. CONCLUSION: Conclusions: The study showed efficiency of combination medications to prevent breast cancer cell development by preventing cell growth.

Unveiling the Secrets of Acinetobacter baumannii: Resistance, Current Treatments, and Future Innovations.

Acinetobacter baumannii represents a significant concern in nosocomial settings, particularly in critically ill patients who are forced to remain in hospital for extended periods. The challenge of managing and preventing this organism is further compounded by its increasing ability to develop resistance due to its extraordinary genomic plasticity, particularly in response to adverse environmental conditions. Its recognition as a significant public health risk has provided a significant impetus for the identification of new therapeutic approaches and infection control strategies. Indeed, currently used antimicrobial agents are gradually losing their efficacy, neutralized by newer and newer mechanisms of bacterial resistance, especially to carbapenem antibiotics. A deep understanding of the underlying molecular mechanisms is urgently needed to shed light on the properties that allow A. baumannii enormous resilience against standard therapies. Among the most promising alternatives under investigation are the combination sulbactam/durlobactam, cefepime/zidebactam, imipenem/funobactam, xeruborbactam, and the newest molecules such as novel polymyxins or zosurabalpin. Furthermore, the potential of phage therapy, as well as deep learning and artificial intelligence, offer a complementary approach that could be particularly useful in cases where traditional strategies fail. The fight against A. baumannii is not confined to the microcosm of microbiological research or hospital wards; instead, it is a broader public health dilemma that demands a coordinated, global response.

Mycobacterium gordoniasis of the cervical lymph nodes: A case report.

BACKGROUND: Owing to the advancement in bacterial identification techniques, the detection rate of non-tuberculous mycobacterium (NTM) has been on the rise. Different from Mycobacterium tuberculosis, the clinical symptoms of NTM are not easily detected, and the clinical efficacy and prognosis are somewhat heterogeneous. To report a case of Mycobacterium gordoniasis of cervical lymph node diagnosed in Anhui Chest Hospital in July 2022. CASE SUMMARY: Upon examination, the patient who weighed 67.5 kg, was human immunodeficiency virus negative, healthy, without hypertension, diabetes, heart disease and other basic diseases microscopic analysis revealed granulomatous inflammation with coagulation necrosis in the lymphocyte, and tuberculosis was not ruled out. Plain computed tomography scans of the neck and chest indicated the presence of a single grayish-yellow and grayish-brown tissue, the dimensions of which was top of form 10.5 cm × 3.0 cm × 1.5 cm. After pathological consultation in our hospital, the diagnosis was confirmed as NTM infection. CONCLUSION: This case report and the clinical epidemiological research on improving NTM have important guiding significance for improving decision-making in clinical treatments.

Hypoxia within the glioblastoma tumor microenvironment: a master saboteur of novel treatments.

Glioblastoma (GBM) tumors are the most aggressive primary brain tumors in adults that, despite maximum treatment, carry a dismal prognosis. GBM tumors exhibit tissue hypoxia, which promotes tumor aggressiveness and maintenance of glioma stem cells and creates an overall immunosuppressive landscape. This article reviews how hypoxic conditions overlap with inflammatory responses, favoring the proliferation of immunosuppressive cells and inhibiting cytotoxic T cell development. Immunotherapies, including vaccines, immune checkpoint inhibitors, and CAR-T cell therapy, represent promising avenues for GBM treatment. However, challenges such as tumor heterogeneity, immunosuppressive TME, and BBB restrictiveness hinder their effectiveness. Strategies to address these challenges, including combination therapies and targeting hypoxia, are actively being explored to improve outcomes for GBM patients. Targeting hypoxia in combination with immunotherapy represents a potential strategy to enhance treatment efficacy.

Acceptance of AI in Health Care for Short- and Long-Term Treatments: Pilot Development Study of an Integrated Theoretical Model.

BACKGROUND: As digital technologies and especially artificial intelligence (AI) become increasingly important in health care, it is essential to determine whether and why potential users intend to use related health information systems (HIS). Several theories exist, but they focus mainly on aspects of health care or information systems, in addition to general psychological theories, and hence provide a small number of variables to explain future behavior. Thus, research that provides a larger number of variables by combining several theories from health care, information systems, and psychology is necessary. OBJECTIVE: This study aims to investigate the intention to use new HIS for decisions concerning short- and long-term medical treatments using an integrated approach with several variables to explain future behavior. METHODS: We developed an integrated theoretical model based on theories from health care, information systems, and psychology that allowed us to analyze the duality approach of adaptive and nonadaptive appraisals and their influence on the intention to use HIS. We applied the integrated theoretical model to the short-term treatment using AI-based HIS for surgery and the long-term treatment of diabetes tracking using survey data with structured equation modeling. To differentiate between certain levels of AI involvement, we used several scenarios that include treatments by physicians only, physicians with AI support, and AI only to understand how individuals perceive the influence of AI. RESULTS: Our results showed that for short- and long-term treatments, the variables perceived threats, fear (disease), perceived efficacy, attitude (HIS), and perceived norms are important to consider when determining the intention to use AI-based HIS. Furthermore, the results revealed that perceived efficacy and attitude (HIS) are the most important variables to determine intention to use for all treatments and scenarios. In contrast, abilities (HIS) were important for short-term treatments only. For our 9 scenarios, adaptive and nonadaptive appraisals were both important to determine intention to use, depending on whether the treatment is known. Furthermore, we determined R² values that varied between 57.9% and 81.7% for our scenarios, which showed that the explanation power of our model is medium to good. CONCLUSIONS: We contribute to HIS literature by highlighting the importance of integrating disease- and technology-related factors and by providing an integrated theoretical model. As such, we show how adaptive and nonadaptive appraisals should be arranged to report on medical decisions in the future, especially in the short and long terms. Physicians and HIS developers can use our insights to identify promising rationale for HIS adoption concerning short- and long-term treatments and adapt and develop HIS accordingly. Specifically, HIS developers should ensure that future HIS act in terms of HIS functions, as our study shows that efficient HIS lead to a positive attitude toward the HIS and ultimately to a higher intention to use.

Digital-assisted multidisciplinary treatment for complex occlusal rehabilitation: an 18-month follow-up case report.

BACKGROUND: This case report highlights the importance of standardized and fully digital sequential treatment in complex occlusal rehabilitation cases. To fully resolve the patient's dental needs, such cases often require multidisciplinary interventions including periodontal therapy, endodontic treatment, anterior esthetics, implant restoration, and prosthetic rehabilitation. A fully digital workflow (including facial scanners, intraoral scanners, jaw motion tracking systems, virtual articulators, and computer-aided design software) streamlined the complex treatment, enhancing workflow simplicity, efficiency, visibility, and precision. CASE PRESENTATION: The patient presented with decreased chewing efficiency of the upper and lower prostheses, along with unsatisfactory esthetic appearance of the anterior teeth. After physical examination and radiological assessment, this complex occlusal rehabilitation case required periodontal therapy, anterior esthetic enhancement, implant restoration, and fixed prosthetic rehabilitation. Therefore, a fully digital workflow was adopted. Full-crown prostheses were placed on teeth 13, 23, and 34; a fixed bridge encompassed positions 32 to 42, and single implant crowns were placed on teeth 35 and 36. Implant-supported fixed bridges were constructed for teeth 12 to 22 and 44 to 46, anchored by implants at teeth 12, 22, 44, and 46. All definitive prostheses were fabricated from zirconia ceramics, chosen for their durability and esthetic characteristics. Finally, restorations with satisfactory esthetic and functional characteristics were seated, preserving the tooth and its supporting structures. During treatment and follow-up, the T-scan occlusal analysis system was utilized to continuously monitor and guide the adjustment of occlusal distribution across the patient's dental arches. After 18 months, the patient remains satisfied with the definitive restorations. CONCLUSIONS: This report is intended to help dentists understand and implement standardized and fully digital workflows during the management of complex occlusal rehabilitation cases; it may also facilitate harmonious integration of esthetic and functional characteristics.

Anorexia Nervosa Across the Lifespan: A Review of Recent Literature.

In this review, the authors provide an update on the understanding of anorexia nervosa (AN) across the lifespan. Focusing on key pieces of literature from the past 5 years, this review summarizes recent updates to DSM-5 within the domain of AN, including the addition of a new AN diagnosis: atypical anorexia. Additional sections covered in this review include improvements in the epidemiological understanding of AN across the developmental spectrum, treatment approaches that have been established as gold standard as well as new directions recently explored in treatment, and recent advancements in the biopsychosocial underpinnings of AN. Altogether, although this review captures several advancements in the field's overall conceptualization of AN, several key areas of treatment and diagnostic capacity continue to require additional focus and research.

Computational insights into survival durations and prehospital interventions in accidental cold-water immersion: A comprehensive analysis of fresh and saltwater temperatures.

This study examines the complex relationship between scenarios of cold-water immersion, survival durations, and prehospital interventions. It utilizes computational modeling methods to shed light on how different water temperatures affect individuals facing accidental cold-water immersion incidents. The analysis reveals significant variations in survival times based on water temperature. For example, subjects immersed in water at temperatures of 5 °C, 2 °C, and 0 °C had average survival times of 136, 113, and 100 min, respectively, under stable conditions. In flowing water at the same temperatures, survival times decreased to 119, 92, and 81 min, indicating the impact of water movement on cooling rates and survival durations. Likewise, individuals immersed in saltwater at temperatures of 5 °C, 2 °C, 0 °C, and -2 °C showed average survival times of 111, 88, 80, and 66 min, respectively, in static conditions. In flowing saltwater at the same temperatures, survival times decreased to 98, 74, 68, and 57 min, highlighting the influence of water flow on cooling rates and survival durations. A comparison between immersion in pure water and saltwater at 2 °C revealed survival times of 113 and 88 min under stable conditions and 92 and 74 min under dynamic conditions, emphasizing the role of water composition in survival outcomes. The study also challenges the notion that the demise of the Titanic's passengers and crew resulted from hypothermia, asserting instead that severe thermal shock was the primary cause. These numerical findings underscore the importance of considering water temperature, flow dynamics, and prompt medical responses in cold-water emergencies to enhance survival prospects. The study identifies water within the range of 41-43 °C as the most effective active external rewarming fluid for critical hypothermal conditions. By quantifying the impact of these variables on survival times, the study provides data-driven recommendations to improve emergency protocols and outcomes for individuals facing cold-water immersion incidents.

Improving protein extraction and peptide production from Chlorella vulgaris using combined mechanical/physical and enzymatic pre-treatments.

Chlorella vulgaris is a microalga rich in proteins with potential applications in food and feed industries. However, the presence of a cellulose-containing cell wall, which is a major barrier to protein extraction, together with fibroproteinaceous complexes, limits the bioaccessibility of nutritional and bioactive proteins and peptides from C. vulgaris biomass. Therefore, this study aimed to evaluate the effect of different mechanical/physical pre-treatments (bead milling, extrusion, freeze-drying, heating, microwave and sonication) combined or not with enzymatic treatments (commercial trypsin and pancreatin) on protein extraction and peptide formation from a C. vulgaris suspension. The amount of total protein and peptides released to the supernatant was quantified by Bradford and o-phthaldialdehyde assays, respectively. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis was used to analyse the extracted protein fractions. The results showed that extrusion caused a 3-fold increase in total peptides (p < 0.001) compared to no-pretreatment, and trypsin increased peptides formed in bead-milled (p = 0.020) and freeze-dried (p = 0.021) microalga relative to those pre-treatments alone. Some pre-treatments, such as bead milling and microwave, were effective in releasing specific protein fractions, particularly those from 32 to 40 kDa (up to 1.2-fold), compared to control. Pancreatin combined with bead milling decreased 32 to 40 kDa- and 26 kDa-protein fractions (p < 0.010) compared with the sole use of mechanical treatment, whereas the same enzyme mixture associated with microwave produced a similar result for 26 kDa-protein fraction (p = 0.023). Pancreatin also effectively reduced the total protein fraction released after pre-treatment with sonication (p = 0.013). These findings suggest that combining different pre-treatments and enzymatic treatments could improve protein extraction from C. vulgaris biomass, providing a useful approach for the development of sustainable protein sources. The present results highlight the need for further studies to assess the efficacy of extrusion in improving the bioaccessibility of C. vulgaris proteins in monogastric animals' diets.

Research landscape and pharmacological mechanisms of traditional Chinese medicines in treating and preventing urolithiasis: Unearthing an anti-urolithic treasure trove.

ETHNOPHARMACOLOGICAL RELEVANCE: Urolithiasis represents a predominant concern within urology due to its high recurrence rate and consequential surgical complications. Traditional Chinese Medicine (TCM), with a history spanning over 2000 years in treating kidney diseases, not only offers a less invasive and cost-effective option for treating and preventing urolithiasis, but also serves as a pharmacological treasure trove for the development of anti-urolithic drugs. AIM OF THE STUDY: With the continuous deepening of research on the anti-urolithic effects of Chinese medicines, the pharmacological mechanisms of TCMs against urolithiasis are continuously evolving. Therefore, it is essential to summarize the current research status, clinical effectiveness, and mechanisms of TCM in treating and preventing urolithiasis, to ascertain its potential in anti-urolithic treatments, and to provide a reference for future anti-urolithiasis drug research. METHODS: The electronic databases such as PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) have been utilized to retrieve relevant literature spanning from 2000 to September 2023, using keywords "Traditional Chinese Medicine" and "Urolithiasis". Then we conducted a visual analysis of the current status of related research, as well as a systematic organization of the therapeutic effects and underlying mechanisms of anti-urolithic TCMs. RESULTS: Through the organization of research models, therapeutic effects, and active ingredients of 31 potential anti-urolithic TCMs, we have systematically summarized the underlying mechanisms of TCMs in management of urolithiasis. Mechanistically, Chinese herbs facilitate stone expulsion by enhancing diuresis, instigating anti-spasmodic effects, and promoting ureteral peristalsis when addressing calculi. They also harbor the potential to dissolve pre-existing stones. In terms of stone recurrence prevention, TCM compounds obstruct stone formation through targeting the sequence of crystal adhesion, nucleation, growth, and aggregation to inhibit stone formation. Additionally, TCM's significant roles include stifling oxidative stress, augmenting urinary stone inhibitors, and harmonizing oxalate metabolism, all of which are critical actions in stone prevention. CONCLUSION: The anti-urolithic mechanism of TCM is multifaceted. Investigating the anti-urolithiasis mechanisms of TCM not only illuminates the potential of Chinese medicine in treating and preventing urolithiasis, but also uncovers active molecules and targets for drug treatment against calculus formation.

Adsorbent based on MOF-5/cellulose aerogel composite for adsorption of organic dyes from wastewater.

Industries persistently contribute to environmental pollution by releasing a multitude of harmful substances, including organic dyes, which represent a significant hazard to human health. As a result, the demand for effective adsorbents in wastewater treatment technology is steadily increasing so as to mitigate or eradicate these environmental risks. In response to this challenge, we have developed an advanced composite known as MOF-5/Cellulose aerogel, utilizing the Pampas plant as a natural material in the production of cellulose aerogel. Our investigation focused on analyzing the adsorption and flexibility characteristics of this novel composite for organic dye removal. Additionally, we conducted tests to assess the aerogel's reusability and determined that its absorption rate remained consistent, with the adsorption capacity of the MOF-5/cellulose aerogel composite only experiencing a marginal 5% reduction. Characterization of the material was conducted through XRD analysis, revealing the cubic structure of MOF aerogel particles under scanning electron microscopy. Our study unequivocally demonstrates the superior adsorption capabilities of the MOF-5/cellulose aerogel composite, particularly evident in its efficient removal of acid blue dye, as evaluated meticulously using UV-Vis spectrophotometric techniques. Notably, our findings revealed an impressive 96% absorption rate for the anionic dye under acidic pH conditions. Furthermore, the synthesized MOF-5/cellulose aerogel composite exhibited Langmuir isotherm behavior and followed pseudo-second-order kinetics during the absorption process. With its remarkable absorption efficiency, MOF-5/cellulose aerogel composites are poised to emerge as leading adsorbents for water purification and various other applications.

Emerging treatment landscape for Guillain-Barré Syndrome (GBS): what's new?

INTRODUCTION: Guillain-Barré syndrome (GBS) is a monophasic immune neuropathic disorder characterized by acute paralysis. A significant portion of patients are left with residual deficits, which presents a considerable global healthcare challenge. The precise mechanisms underlying GBS pathogenesis are not fully elucidated. Recent studies have focused on postinfectious molecular mimicry and identified involvement of IgG autoantibodies and innate immune effectors in GBS. Intravenous immunoglobulins (IVIg) and plasma exchange (PE) are two established evidence-based immunomodulatory treatments for GBS, but a significant proportion of GBS patients fails to respond adequately to either therapy. This emphasizes an urgent need for novel and more potent treatments. AREAS COVERED: We discuss novel immunomodulatory therapies presently at different phases of preclinical and clinical investigation. Some drugs in development target pathophysiologic mechanisms such as IgG autoantibody catabolism and complement activation, which are relevant to GBS. EXPERT OPINION: There is an unmet need for more effective immune therapies for GBS. New immunomodulatory therapies under development may provide more potent options for GBS patients who do not respond to IVIg or PE. Future directions may include incorporating neuroprotective interventions based on evolving understanding of mechanisms underlying nerve injury and axonal degeneration.

Determining sample size in a personalized randomized controlled (PRACTical) trial.

In clinical settings with no commonly accepted standard-of-care, multiple treatment regimens are potentially useful, but some treatments may not be appropriate for some patients. A personalized randomized controlled trial (PRACTical) design has been proposed for this setting. For a network of treatments, each patient is randomized only among treatments which are appropriate for them. The aim is to produce treatment rankings that can inform clinical decisions about treatment choices for individual patients. Here we propose methods for determining sample size in a PRACTical design, since standard power-based methods are not applicable. We derive a sample size by evaluating information gained from trials of varying sizes. For a binary outcome, we quantify how many adverse outcomes would be prevented by choosing the top-ranked treatment for each patient based on trial results rather than choosing a random treatment from the appropriate personalized randomization list. In simulations, we evaluate three performance measures: mean reduction in adverse outcomes using sample information, proportion of simulated patients for whom the top-ranked treatment performed as well or almost as well as the best appropriate treatment, and proportion of simulated trials in which the top-ranked treatment performed better than a randomly chosen treatment. We apply the methods to a trial evaluating eight different combination antibiotic regimens for neonatal sepsis (NeoSep1), in which a PRACTical design addresses varying patterns of antibiotic choice based on disease characteristics and resistance. Our proposed approach produces results that are more relevant to complex decision making by clinicians and policy makers.

Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.

Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.

Strategies of Pharmacological Repositioning for the Treatment of Medically Relevant Mycoses.

Fungal infections represent a worldwide concern for public health, due to their prevalence and significant increase in cases each year. Among the most frequent mycoses are those caused by members of the genera Candida, Cryptococcus, Aspergillus, Histoplasma, Pneumocystis, Mucor, and Sporothrix, which have been treated for years with conventional antifungal drugs, such as flucytosine, azoles, polyenes, and echinocandins. However, these microorganisms have acquired the ability to evade the mechanisms of action of these drugs, thus hindering their treatment. Among the most common evasion mechanisms are alterations in sterol biosynthesis, modifications of drug transport through the cell wall and membrane, alterations of drug targets, phenotypic plasticity, horizontal gene transfer, and chromosomal aneuploidies. Taking into account these problems, some research groups have sought new therapeutic alternatives based on drug repositioning. Through repositioning, it is possible to use existing pharmacological compounds for which their mechanism of action is already established for other diseases, and thus exploit their potential antifungal activity. The advantage offered by these drugs is that they may be less prone to resistance. In this article, a comprehensive review was carried out to highlight the most relevant repositioning drugs to treat fungal infections. These include antibiotics, antivirals, anthelmintics, statins, and anti-inflammatory drugs.

Updates on Topical Dyad and Triple Combination Therapies Approved for Acne Vulgaris.

Acne vulgaris is a multifaceted disease characterized by inflammatory and noninflammatory lesions. Topical combination therapies offer a multifaceted approach to acne treatment, with synergistic effects and a broad spectrum of action against multiple factors in acne pathogenesis in one single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene, a combination therapy consisting of clindamycin phosphate 1.2%, benzoyl peroxide (BPO) 3.1%, and adapalene 0.15%, is a novel treatment, the only FDA-approved triple combination drug that offers effective treatment of acne vulgaris. This review aims to provide information on clindamycin phosphate/benzoyl peroxide/adapalene and review the literature on combination topical acne medications approved in the United States. This search was conducted on topical combination therapies for acne, their efficacy, adverse effects, and impacts on quality of life with a specific focus on the newly approved clindamycin phosphate/benzoyl peroxide/adapalene and its sub-component dyads, along with other combinations. PubMed, SCOPUS, Embase, Cochrane, and Web of Science databases were searched for publications in 2018-2023. Primary sources were given priority, and secondary sources such as other reviews were considered to supplement any missing information. It was found that various topical dyad and triad combinations exist for acne vulgaris, including adapalene/BPO, tazarotene/clindamycin, clindamycin/BPO, adapalene/clindamycin, topical tretinoin/azelaic acid, topical tretinoin/BPO, and clindamycin phosphate/benzoyl peroxide/adapalene. Dyad and triple combinations represent a promising, convenient solution for acne management, potentially improving patient adherence due to its single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene exhibited significantly high efficacy in treating both inflammatory and noninflammatory lesions, a minimal side effect profile, although no significant changes in quality-of-life measures. Further research is indicated to assess its long-term efficacy and impact on other acne metrics such as cost, scarring, psychosocial implications, and impact on diverse patient populations.