Rapidly Evolving Pre- and Post-surgical Systemic Treatment of Melanoma
Melanoma therapeutics continues to advance with combination adjuvant approaches now investigating anti-PD1 with lymphocyte activation gene 3 (LAG3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and individualized neoantigen therapies. How this progress will be integrated into the management of a unique patient to reduce recurrence, limit toxicity, and avoid over-treatment will dominate clinical research and patient care over the next decade.
KEY FINDINGS: Melanoma therapeutics continues to advance with combination adjuvant approaches now investigating anti-PD1 with lymphocyte activation gene 3 (LAG3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and individualized neoantigen therapies. How this progress will be integrated into the management of a unique patient to reduce recurrence, limit toxicity, and avoid over-treatment will dominate clinical research and patient care over the next decade.
BACKGROUND: With the development of effective BRAF-targeted and immune-checkpoint immunotherapies for metastatic melanoma, clinical trials are moving these treatments into earlier adjuvant and perioperative settings. BRAF-targeted therapy is a standard of care in resected stage III-IV melanoma, while anti-programmed death-1 (PD1) immunotherapy is now a standard of care option in resected stage IIB through IV disease.
DETAILS: With both modalities, recurrence-free survival and distant-metastasis-free survival are improved by a relative 35-50%, yet no improvement in overall survival has been demonstrated. Neoadjuvant anti-PD1 therapy improves event-free survival by approximately an absolute 23%, although improvements in overall survival have yet to be demonstrated. Understanding which patients are most likely to recur and which are most likely to benefit from treatment is now the highest priority question in the field. Biomarker analyses, such as gene expression profiling of the primary lesion and circulating DNA, are preliminarily exciting as potential biomarkers, though each has drawbacks. As in the setting of metastatic disease, markers that inform positive outcomes include interferon-γ gene expression, PD-L1, and high tumor mutational burden, while negative predictors of outcome include circulating factors such as lactate dehydrogenase, interleukin-8, and C-reactive protein. Integrating and validating these markers into clinically relevant models is thus a high priority.
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Copyright © Springer Nature. All rights reserved.
Source: Augustin, R. C. and Luke, J. J. (2024). Rapidly Evolving Pre- and Post-surgical Systemic Treatment of Melanoma. American Journal of Clinical Dermatology. Published: March, 2024. DOI: 10.1007/s40257-024-00852-5.
Promising Drug Candidates and Emerging Therapeutic Strategies Against Candida auris
Emerging therapies for Candida auris extend beyond conventional antifungal agents and include repurposed drugs, novel antifungal compounds, vaccines, antimicrobial peptides, and nanotechnology-based approaches. While further clinical validation is needed, these strategies may help address the growing challenge of multidrug-resistant C. auris infections.
KEY FINDINGS: This review underscores the expanding pipeline of therapeutic strategies targeting Candida auris, ranging from repurposed medications and next-generation antifungal agents to vaccines, antimicrobial peptides, nanoparticle formulations, and innovative environmental control measures. Although no single therapy has emerged as a definitive solution, compounds such as ibrexafungerp (SCY-078), ATI-2307, and fosmanogepix, together with drug repurposing and bioinspired approaches, represent promising avenues for addressing multidrug-resistant C. auris infections. Continued translational research and clinical evaluation remain essential to establish safe and effective treatment options for this increasingly important fungal pathogen.
BACKGROUND: Candida auris has rapidly emerged as a multidrug-resistant fungal pathogen of global concern since its first identification in 2009. The organism is associated with healthcare-associated outbreaks, high transmissibility, frequent misidentification, and severe invasive infections, with reported mortality rates ranging from 35% to 72%. Resistance to currently available antifungal agents further complicates treatment, with approximately 90% of isolates resistant to fluconazole, around 30% resistant to amphotericin B, and fewer than 5% resistant to echinocandins. These challenges have accelerated efforts to identify novel antifungal therapies and alternative treatment strategies.
DETAILS: This publication is a comprehensive narrative review that summarizes advances in antifungal research targeting C. auris over the preceding decade. The authors evaluated emerging therapeutic approaches from a medicinal chemistry perspective, including drug repurposing, combination therapy, novel antifungal agents, natural products, metal-based compounds, nanoparticles, vaccines, antimicrobial peptides, and environmental decontamination strategies. The review also examined chemical and physicochemical characteristics of promising compounds, including lipophilicity and topological polar surface area, to identify structural features that may facilitate future antifungal drug development. The review highlights several promising therapeutic candidates with activity against multidrug-resistant C. auris. Drug repurposing identified multiple agents with antifungal or antibiofilm activity, including sertraline, miltefosine, iodoquinol, octenidine dihydrochloride, taurolidine, and bensulfuron methyl. Miltefosine demonstrated fungicidal and antibiofilm activity, while encapsulation within alginate nanoparticles reduced toxicity and improved survival in an infected Galleria mellonella model. The NDV-3A vaccine generated cross-reactive antibodies against C. auris and protected neutropenic mice, with additive efficacy when combined with micafungin.
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Among novel antifungal agents, SCY-078 (ibrexafungerp), an orally available 1,3-ß-D-glucan synthesis inhibitor, demonstrated potent activity against C. auris, with an MIC90 of 1 mg/L and MIC50 and MIC90 values of 0.5 µg/mL and 1 µg/mL, respectively, across 100 isolates representing the four major clades. More than 150 strains with diverse resistance profiles were subsequently shown to be uniformly susceptible to SCY-078, and the agent remained active against pan-resistant isolates while also exhibiting antibiofilm activity.
Additional investigational therapies also demonstrated encouraging preclinical activity. The arylamidine T-2307 (ATI-2307) exhibited in vitro MIC values ranging from 0.125 to 4 µg/mL and improved survival while reducing kidney fungal burden in murine infection models following 3 mg/kg once-daily subcutaneous treatment. Other experimental approaches included antimicrobial peptides, ceragenins, fluorinated hydrazone derivatives, and novel chemical scaffolds designed to overcome existing resistance mechanisms.
Copyright © Skyscape. All rights reserved.
Source: Billamboz, M., Fatima, Z., Hameed, S., et al. Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris. Microorganisms. 2021; 9(3): 634. Published: March 18, 2021. DOI: 10.3390/microorganisms9030634.
Prompt and Intensive Antiviral Chemoprophylaxis in Nursing Home Influenza Outbreaks
Findings suggest intensive chemoprophylaxis of 70% or more of residents in response to influenza outbreaks in NHs within the first 2 days is associated with a lower 14-day risk of hospitalization among residents, with additional evidence to support a benefit when 60% or more or 80% or more of residents receive chemoprophylaxis. These findings could strengthen evidence-based recommendations to inform best practices in managing influenza outbreaks in NHs.
KEY FINDINGS: Study results suggest that clinicians should initiate antiviral chemoprophylaxis for at least 70% of eligible NH residents within 2 days of outbreak detection to lower risk of hospitalization.
BACKGROUND: Influenza outbreaks in nursing homes (NHs) pose a substantial threat to older adults, often resulting in morbidity and mortality. The Centers for Disease Control and Prevention (CDC) and the Infectious Diseases Society of America (IDSA) recommend prompt postexposure prophylaxis, also termed chemoprophylaxis or prophylaxis with oseltamivir, for all residents who are not ill to limit influenza spread in NHs. Purpose of the study is to examine whether initiating antiviral chemoprophylaxis for 70% or more of eligible NH residents within 2 days of influenza outbreak detection is associated with lower all-cause mortality and hospitalization at 14 and 30 days.
DETAILS: Retrospective cohort study using a sequential cluster-randomized target trial emulation and randomize-censor-weight approach for influenza outbreaks (September 1, 2018-May 31, 2022) in 12 US NH corporations. Eligibility criteria were age 18 years or older, present on the outbreak-detection day, no antiviral use in the preceding 7 days, no influenza in the past 14 days, and complete baseline data. Residents were followed up until hospitalization or death, an NH discharge to a nonacute-care location, or the end of follow-up. Data were analyzed from February 2023 to January 2026.
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Exposures: Intensive antiviral chemoprophylaxis with oseltamivir (>=70% of eligible residents within 2 days of outbreak detection) or nonintensive antiviral chemoprophylaxis (0% to <70% of eligible residents).
Outcomes were all-cause death and hospitalizations within 14 and 30 days of outbreak detection. Discrete-time hazard models with pooled logistic regression were applied to estimate weighted risks, risk differences (RDs), and risk ratios (RRs).
Among 404 outbreaks in 318 NHs, 35,086 resident-trial observations (29,683 residents; median age 78 [IQR, 68- 86] years; 60% women; 81% White; 76% vaccinated) met eligibility criteria. Intensive oseltamivir prophylaxis was randomized to 17,155 observations; 17,931 were randomized to nonintensive care. At 14 days, intensive prophylaxis vs nonintensive yielded an RD of -0.06% (95% CI, -0.73% to 0.93%) and an RR of 0.96 (95% CI, 0.56-1.57) for death, and an RD of -0.96% (95% CI, -1.78% to -0.19%) and an RR of 0.79 (95% CI, 0.64-0.96) for hospitalization. At 30 days, the hospitalization differences persisted but were less precise and there continued to be no difference in death.
Copyright © American Medical Association. All Rights Reserved.
Source: Silva, J. B. B., Hsieh, H. T., Howe, C. J., et al. Prompt and Intensive Antiviral Chemoprophylaxis in Nursing Home Influenza Outbreaks. JAMA Internal Medicine.. 2026; 186(6): 714-722. Published: June, 2026. DOI: 10.1001/jamainternmed.2026.0401
Safety and Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in Patients with Psoriasis and Type 2 Diabetes Mellitus
Treatment with SGLT2i was associated with favorable clinical outcomes in patients with psoriasis and comorbid T2DM. These findings support investigation of SGLT2i as an adjunct therapy in this population.
KEY FINDINGS: Treatment with SGLT2i was associated with favorable clinical outcomes in patients with psoriasis and comorbid T2DM. These findings support investigation of SGLT2i as an adjunct therapy in this population.
BACKGROUND: Psoriasis is a chronic inflammatory disease associated with multiple comorbidities, including:
- Type 2 diabetes mellitus (T2DM)
- Cardiovascular disease
- Chronic kidney disease (CKD)
- Psychiatric disorders
- Psoriasis and T2DM share common inflammatory pathways and may increase the risk of developing one another.
- While DPP4 inhibitors (DPP4i) and GLP-1 receptor agonists (GLP1RA) have shown benefits in psoriasis, the impact of SGLT2 inhibitors on psoriasis-related outcomes remained unclear.
Purpose of this study is to evaluate the safety and effectiveness of SGLT2 inhibitors in patients with psoriasis and concomitant T2DM, compared with:
- DPP4 inhibitors (DPP4i)
- GLP-1 receptor agonists (GLP1RA)
DETAILS: This emulated target trial included adults with psoriasis and T2DM initiating SGLT2i, DPP4i, or GLP1RA between 2013 and 2025. SGLT2i initiators were propensity score-matched to DPP4i initiators and GLP1RA initiators, respectively. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the outcomes. A total of 8799 SGLT2i initiators and 8799 matched DPP4i initiators with psoriasis and comorbid T2DM, and 11,550 SGLT2i initiators and 11,550 matched GLP1RA initiators, were included. Compared with DPP4i, treatment with SGLT2i was associated with significantly lower all-cause mortality (HR = 0.633, 95% CI = 0.564-0.711) and reduced risks of emergency visits (HR = 0.915, 95% CI = 0.871-0.961), acute kidney injury (HR = 0.834, 95% CI = 0.759-0.916), chronic kidney disease (HR = 0.866, CI = 0.791-0.949), end-stage renal disease (HR = 0.555, 95% CI = 0.438-0.703), and severe sepsis (HR = 0.689, CI = 0.594-0.799). Compared with GLP1RA, treatment with SGLT2i was associated with reduced risks of asthma (HR = 0.822, 95% CI = 0.713-0.946), depression (HR = 0.887, CI = 0.801-0.983), sleep disorders (HR = 0.856, CI = 0.783-0.936), and malignancies (HR = 0.852, 95% CI = 0.764-0.951).
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Copyright © Elsevier Ltd. All rights reserved.
Source: Cheng, D., Ji, H., Theodosakis, N., et al. Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Psoriasis and Comorbid Type 2 Diabetes: A Population-Based Target Trial Emulation Journal of the American Academy of Dermatology. 2026; 94(6): 1686-1696. Published: June, 2026. DOI: 10.1016/j.jaad.2026.02.008
Corrective and Restorative Dermatology in Cancer Survivors
Advances in cancer therapies have resulted in a growing population of long-term cancer survivors with chronic dermatological sequelae, such as persistent alopecia, nail abnormalities, pigmentary disorders, telangiectasias, scarring, mucosal alterations, and chronic radiation-induced skin changes. Dermatological sequelae may cause functional impairment, psychological distress, altered body image, and reduced quality of life.
KEY FINDINGS: Supportive oncodermatology, originally focused on the acute treatment phase, must evolve to address the long-term needs of the growing cancer survivor population. Preventive strategies, such as scalp cooling during chemotherapy, are vital, as existing treatments for established sequelae like PCIA and radiation-induced scarring have limited efficacy. While topical minoxidil and, more recently, oral minoxidil have shown promise for hair density improvements, and lasers are effective for telangiectasias, the management of many chronic dermatological sequelae remains largely extrapolated from other dermatological conditions rather than specifically validated for cancer survivors. Multidisciplinary follow-up programs are essential to address the complex functional, cosmetic, and psychological needs of these patients.
BACKGROUND: With the increasing effectiveness of modern oncological treatments, the population of cancer survivors is rapidly expanding. Consequently, clinical focus is shifting from the management of acute treatment-related toxicities to the long-term or late sequelae of cancer therapy. Among these, dermatological conditions—such as persistent alopecia, nail disorders, scarring, pigmentary alterations, and chronic radiation-induced skin changes—are highly visible, often persistent, and can significantly impair the quality of life, body image, and psychological well-being of survivors. While supportive oncodermatology is well-established for active treatment settings, structured care during the survivorship phase remains significantly underdeveloped.
DETAILS: This review defines "restorative oncodermatology" as the management of dermatological manifestations persisting for at least six months after the completion of anticancer therapy. Such conditions include both persistent toxicities that are slow to regress and true long-term sequelae resulting from treatment-induced tissue damage. Epidemiological data indicates that these issues are prevalent; for example, up to 59% of adult survivors of childhood cancer report chronic skin-related problems, and approximately 30% report visible scarring or disfigurement. Specific conditions addressed include persistent chemotherapy-induced alopecia (PCIA), which affects between 1% to approximately 40% of patients depending on the regimen , and radiation-induced scarring alopecia, where a threshold of approximately 36 Gy is associated with a 50% probability of severe alopecia. The article also explores the management of chronic nail changes, pigmentary alterations, hair growth disorders like hirsutism and hypertrichosis, and mucosal sequelae. Despite the high prevalence and impact of these dermatological sequelae, dedicated survivorship-oriented dermatological care is rarely implemented. There is an urgent requirement to improve knowledge in this field and provide specialized care, particularly for childhood and adolescent cancer survivors, who are especially vulnerable to the effects of these conditions on their physical appearance and identity development. Dermatologists must play a central role in long-term survivorship by performing surveillance for secondary skin cancers and delivering restorative treatments that help patients navigate life after cancer.
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Efficacy of Low-Dose Oral Isotretinoin Combined with Fractional Microneedle Radiofrequency Versus Low-Dose Oral Isotretinoin Monotherapy in the Treatment of Moderate-To-Severe Acne Vulgaris
Early active treatment with isotretinoin and FMRF is safe and better than isotretinoin monotherapy over 44 weeks regarding severity, reduced erythema, and improved surface roughness in moderate-to-severe acne vulgaris. This encourages early and effective treatment of acne to mitigate acne scarring and improve patients' quality of life.
Summary
A Randomized Controlled Comparative Study
[Posted 19/May/2026]
AUDIENCE: General Surgery, Family Medicine
KEY FINDINGS: Early active treatment with isotretinoin and FMRF is safe and better than isotretinoin monotherapy over 44 weeks regarding severity, reduced erythema, and improved surface roughness in moderate-to-severe acne vulgaris. This encourages early and effective treatment of acne to mitigate acne scarring and improve patients' quality of life.
BACKGROUND: Oral isotretinoin is the standard therapy for severe acne. However, scarring may persist. Fractional microneedling radiofrequency (FMRF) improves both inflammatory lesions and scars with minimal downtime. In this study, we compare isotretinoin monotherapy and concurrent isotretinoin and FMRF for active acne regarding clinical outcomes. The GAGS scores of isotretinoin and FMRF were significantly lower than those of isotretinoin monotherapy from weeks 12-44 (-79.69% vs. -60.34% at week 44, respectively; p < 0.001). Isotretinoin and FMRF showed significantly greater lesion count reductions than isotretinoin monotherapy at follow-up visits from weeks 12-44. Isotretinoin and FMRF showed significantly lower hemoglobin levels than isotretinoin monotherapy at weeks 32 and 44 (p = 0.029 and p < 0.001, respectively). Skin surface roughness improved substantially and persistently from week 12-44.
DETAILS: In this parallel two-group comparative study, patients received either low-dose isotretinoin monotherapy for 20 weeks (n = 34) or low-dose isotretinoin concurrently with 5 monthly FMRF sessions (n = 36). Outcomes were assessed at baseline and weeks 12, 20, 24, 32, and 44. The primary endpoints were Global Acne Grading System (GAGS) scores and inflammatory/non-inflammatory lesion counts. Secondary endpoints were hemoglobin indices and skin roughness.
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Copyright © Wiley Periodicals LLC. All rights reserved
Source: Disphanurat, W., Leeyangyuen, P,, and Srisantithum, B. Efficacy of Low-Dose Oral Isotretinoin Combined With Fractional Microneedle Radiofrequency Versus Low-Dose Oral Isotretinoin Monotherapy in the Treatment of Moderate-To-Severe Acne Vulgaris: A Randomized Controlled Comparative Study. Lasers in Surgery and Medicine. 2026; 58(4): 321-330. Published: April, 2026. DOI: 10.1002/lsm.70120.
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