Chemsex involves the use of psychoactive substances to facilitate or enhance sexual activity, particularly among gay, bisexual, and other men who have sex with men (GBMSM). Common substances used include methamphetamine, gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL), mephedrone, ketamine, inhaled nitrites ('poppers'), and cocaine, all of which are linked to various dermatological complications. Dermatologists are often the first to recognize skin and mucosal manifestations in chemsex users, providing an opportunity for timely intervention and risk reduction. A targeted literature search until January 2026 was conducted using PubMed/MEDLINE to identify relevant publications on chemsex-associated dermatological manifestations. The studies included were observational, case series, case reports and clinical guidelines, focusing on the clinical presentation, substances involved and routes of administration. Cutaneous and mucosal lesions vary depending on the substance and route of administration. Poppers dermatitis, commonly seen in GBMSM, is a well-defined manifestation and often misdiagnosed as impetigo. 3,4-Methylenedioxymethamphetamine (MDMA), often used in chemsex, leads to oral mucositis and painful aphthous-like ulcers due to its acute effects, such as bruxism and xerostomia. Injection-related lesions from substances like mephedrone and ketamine are particularly concerning, often resembling infectious or vasculitic processes and frequently leading to delayed diagnoses. Cocaine use, especially when combined with levamisole, can cause cutaneous necrosis, vasculitis and soft tissue infections. GHB/GBL use may cause traumatic genital and perianal injuries due to reduced pain sensitivity, while alprostadil injections can result in localized oedema, haematomas or fibrosis. Lastly, constricting devices used in chemsex settings can lead to mechanical trauma, ischaemic injury and chronic complications like fibrosis and penile deformities. Chemsex is a significant public health concern with dermatological implications. Improved awareness of characteristic cutaneous and mucosal lesions can support earlier recognition, targeted investigation and non-stigmatizing risk-reduction advice and referral. More prospective studies and standardized diagnostic criteria are needed to enhance the management of chemsex-related dermatological and systemic complications.

Retiform purpura (RP) is a morphological pattern of cutaneous ischemia resulting from vascular compromise. Its clinical relevance lies in its orientation toward vasculitis or thrombotic vasculopathy. We report the case of a woman with painful violaceous retiform lesions on the distal lower extremities, Raynaud's phenomenon with a "blue toe" on the hand, and polyarthralgias. Laboratory workup revealed antinuclear antibodies (ANA) 1:2560 (AC-5 pattern), anti-RNP > 240 U/mL, anti-Sm > 320 U/mL, low C4, and negative antineutrophil antibodies (ANCA) and rheumatoid factor. Magnetic resonance imaging showed diffuse muscular edema and bilateral fascial thickening; computed tomography reported reactive adenopathies. Skin biopsy demonstrated ischemic changes consistent with small vessel involvement in a mixed vasculitic/vasculopathic pattern, with epidermal necrosis and intraluminal fibrin. Systemic lupus erythematosus (SLE) with features of small vessel vasculitis was diagnosed. Treatment included methylprednisolone and prednisone pulses, cyclophosphamide, rituximab, and alprostadil for digital ischemia, with clinical improvement. RP may reflect a mixed inflammatory/thrombotic process in the context of overlapping autoimmunity. Deep biopsy, autoimmune profiling, and assessment of prothrombotic state are key axes for decisions regarding immunosuppression and/or antithrombotic strategies. Key Points • Retiform purpura is a high-risk cutaneous pattern that requires early differentiation between vasculitis and thrombotic vasculopathy, as each condition demands divergent therapeutic strategies (immunosuppression versus antithrombotic therapy). • In patients with SLE, cutaneous vasculitis - though uncommon - may present with a dominant ischemic phenotype (retiform purpura, digital ischemia) that initially mimics medium-vessel vasculitis such as polyarteritis nodosa or systemic sclerosis; accurate diagnosis requires integration of clinical, histological, and immunological data. • Management of severe ischemic SLE with a mixed inflammatory/occlusive mechanism may require a parallel approach: intensive immunosuppression to control vascular inflammation, combined with vasoactive and anticoagulant measures to preserve distal perfusion and tissue viability.

Secondary Raynaud's Phenomenon (RP) associated with connective tissue diseases (CTD) frequently presents as critical digital ischemia refractory to standard protocols. This review describes the clinical feasibility of a combined approach involving mechanical (surgical adventitial stripping) and chemical (Botulinum Toxin Type A [BTX-A] and/or prostanoid analogues) sympathectomy. We retrospectively reviewed four patients from tertiary centers in Mexico and Argentina presenting with severe refractory RP. Interventions involved periarterial digital sympathectomy augmented by intradigital BTX-A and/or intravenous (IV) prostanoids. Longitudinal clinical observations were recorded regarding pain reduction using the Visual Analog Scale (VAS), digital ulcer healing, and vascular imaging. Clinical remission was achieved in 3/4 patients. Case one healed a 0.5 cm necrotic lesion following bilateral stripping and 80 IU BTX-A. Case two, achieved complete tissue stabilization at 16-month follow-up; intraoperative angiography confirmed the immediate restoration of digital arch perfusion post-intervention. Case three, presented with a "late" capillaroscopy pattern, maintained a 60-month ulcer-free interval using 80 IU BTX-A and Alprostadil. Case four involved 8/10 ischemic digits; the course was complicated by a radial artery thrombosis requiring a radio-radial venous graft bypass. This patient suffered a relapse with three new distal ulcers immediately following an administrative gap in Bosentan therapy. These hypothesis-generating findings suggest that multimodal sympathectomy is a feasible adjunctive strategy for limb salvage in refractory complicated secondary RP. Current literature enforces these findings supporting the notion for standardized dosing and stepwise approach for future research to support these hypothesis generating views.

BACKGROUND: Cutaneous adverse drug reactions (CADRs) are uncommon but clinically significant complications among patients with congenital heart disease (CHD), particularly those with pulmonary arterial hypertension (PAH) or perioperative hemodynamic instability. The complex pharmacologic regimens required in CHD—often involving prostaglandins, vasodilators, antibiotics, and antiepileptics—predispose patients to idiosyncratic and immune-mediated reactions. Despite increasing recognition of CADRs in cardiovascular medicine, systematic evidence focusing on CHD populations remains limited. METHODS: A systematic search of MEDLINE (PubMed), Embase, Web of Science, and CENTRAL was conducted from database inception to October 31, 2024, covering all types of congenital heart disease, both cyanotic and acyanotic, isolated and syndromic forms. Eligible studies included randomized controlled trials, observational studies, and case reports that reported CADRs in patients with structural CHD, regardless of age or surgical status. Extracted outcomes included type of CADR, implicated drug, temporal association, histopathology, management, and clinical outcome. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist for case reports and case series. RESULTS: Thirteen studies encompassing 22 patients met the inclusion criteria. Most patients (68%) were neonates or infants with duct-dependent congenital heart disease receiving prostaglandin E₁ (alprostadil) for lesions such as transposition of the great arteries, hypoplastic left heart syndrome, and Taussig–Bing anomaly. The most frequently reported CADRs were prostaglandin-associated vasomotor eruptions, including migratory urticaria and erythematous patches (n = 4, 18%), as well as radiographically detected brown fat necrosis and soft-tissue calcification following prolonged prostaglandin infusion (n = 9, 41%). Severe hypersensitivity reactions—including drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome (SJS)—occurred in patients receiving antiepileptics or antibiotics (n = 3, 14%), typically in postoperative or intensive care settings. Additional reports described bosentan-associated indurated erythema in an adult with repaired tetralogy of Fallot and amoxicillin-associated morbilliform exanthem in pediatric patients after surgical repair. Overall, prostaglandin analogs accounted for the majority of implicated drugs (77%), followed by antiepileptics (9%), antibiotics (9%), and pulmonary vasodilators (5%). Methodological quality of the included studies was generally low according to the Joanna Briggs Institute appraisal tools due to descriptive study designs and limited follow-up. CONCLUSIONS: CADRs, though infrequently reported, occur across the therapeutic continuum of CHD management—from neonatal prostaglandin therapy to adult antimicrobial and antiepileptic use. The predominance of prostaglandin-associated reactions underscores the importance of dermatologic and metabolic surveillance during infusion therapy, while severe whereas severe hypersensitivity reactions underscore the interface between cardiology and dermatology. Larger multicenter studies are warranted to clarify incidence, risk factors, and outcomes, guiding safer pharmacologic management in congenital cardiology.

The COVID-19 pandemic has revealed significant disparities in health research across regions, particularly in Latin America. This viewpoint explores the challenges encountered during a randomized clinical trial in Colombia designed to evaluate the effectiveness of intravenous Alprostadil for treating moderate-to-severe COVID-19. The trial, aimed to address the urgent need for effective treatments, ultimately became undermined by bureaucratic barriers. This experience of regulatory delays and prolonged setbacks highlighted broader systemic issues in health research across Latin America, such as tangled regulatory frameworks, insufficient skilled staff, and limited research infrastructure. These obstacles, combined with financial constraints, prevent timely research, impairing Latin America's ability to address health crises independently. To improve health research policies in the region, lessons from countries like Brazil, Argentina, and Chile, where regulatory processes have been streamlined, suggest that reforms promoting efficient approval systems, policy alignment, and enhanced collaboration are vital for strengthening health research capacity in Latin America.

Background and objectives Erectile dysfunction (ED) is a multifactorial disease associated with many medical co-morbidities and risk factors commonly encountered in primary care. Initial management includes lifestyle changes and the treatment of any identifiable conditions. Guidelines exist recommending the assessment and management of sufferers with clear indications for referral to secondary care. With the outbreak of COVID-19, non-urgent medical services, including ED, were suspended, creating a significant waiting list for these patients. The aim of this study was to review the management of men in both primary and secondary care who had been referred to a dedicated ED service. Materials and methods A retrospective review of men referred to secondary care between June 2018 and April 2021 with ED was undertaken, reviewing whether the guidelines published by the National Institute for Health and Care Excellence (NICE) and GP Notebook for the assessment, initial treatment, and referral were followed by the primary care clinician. A secondary aim was to record the outcome of those men after review in a secondary care dedicated ED clinic. Results One hundred and forty-eight men were reviewed in the ED clinic, with 55 men (37.2%) requiring an intervention that was appropriate to have been delivered in primary care. The majority of those (76.3%) were successfully managed with a phosphodiesterase inhibitor. Of those treated in secondary care, almost 60% required a second-line therapy, such as a vacuum device or the administration of alprostadil, with 14 men (15%) necessitating the surgical implantation of a penile prosthesis. Conclusion With a rise in both the prevalence and incidence of ED, primary care physicians have a pivotal role in the screening and initial assessment of patients with ED, with evidence suggesting that a significant proportion can be successfully managed in this setting.

Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.

Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic-ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 10[6] cells/body) or Hank's balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel.