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Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent nodules, abscesses, and sinus tracts that lead to significant morbidity and impaired quality of life. Although both biologic therapies and surgical interventions are effective when used independently, their combined use has gained increasing attention. This systematic review aimed to evaluate the efficacy and safety of combining immunomodulatory therapy with surgical procedures in HS. A conceptual framework was applied that distinguished three modalities of combined treatment according to the temporal relationship between biologic therapy and surgery: pre-biologic surgery, post-induction surgery, and concomitant approaches. A comprehensive search identified eight eligible studies, including 508 patients. Most studies were retrospective and of low methodological quality. Across studies, combination therapy (particularly with adalimumab, secukinumab, or bimekizumab) was generally associated with improved clinical outcomes compared to biologic monotherapy, including higher response rates (Hidradenitis Suppurativa Clinical Response [HiSCR]; 55% reduction in the International Hidradenitis Suppurativa 4 [IHS4-55]), greater reductions in pain, disease flares, and Dermatology Life Quality Index scores. Safety profiles were comparable between groups, with no consistent increase in postoperative complications or serious adverse events. However, key outcomes such as wound healing time were poorly reported. Substantial heterogeneity in study design, treatment protocols, and timing of interventions limited comparability and precluded meta-analysis. Overall, the available evidence preliminarily supports combined medical and surgical treatment as a potentially beneficial and well-tolerated strategy for moderate-to-severe HS, in line with current expert practice. However, given the low quality and substantial heterogeneity of the included studies, these findings should be considered exploratory and require confirmation in higher-quality prospective studies that adopt standardized definitions of combination therapy and report wound healing as a core outcome.
As antiretroviral treatment indications evolved, an increasing proportion of patients have been treated; since 2017, most patients receive antiretroviral treatment, irrespective of their CD4 count, in French Guiana and neighboring countries. In this context, we aimed to model the epidemic and to study the evolution of the estimates of the intervals between HIV-infection and HIV diagnosis in French Guiana. The study was descriptive and comparative. Anonymous data from all persons in the DAT'AIDS HIV cohort based on quality-controlled clinical records was aggregated into yearly statistics between 2000 and 2023. We estimated year of infection using the rate of CD4 decline between the CD4 count at diagnosis and the estimation of the CD4 count at the time of HIV infection. The HIV modelling platform version 3.0.2 used the annual number of new HIV infections, the number of new AIDS cases, the number of new HIV infections that had AIDS, and CD4 strata to compute incidence, number of diagnosed and undiagnosed persons, and diagnostic delay. All indicators improved markedly over time. Incidence declined, diagnostic delay declined, the proportion of undiagnosed patients declined, and deaths declined. However, the estimated interval between HIV infection and diagnosis was heterogenous between groups: It was about 2 years longer among males than among females, and it was about 3 years longer among Surinamese or Brazilian immigrants. Overall, 5% of all persons with HIV were undiagnosed, 9% of diagnosed persons were not on antiretroviral therapy and 6% of those on antiretroviral therapy were in virological failure. For a population of about 4,000 persons with HIV this represents a residual source of transmission. The scaling up of testing, antiretroviral treatment, and preexposure prophylaxis has led to remarkable progress. Nevertheless, further shrinking the reservoir of undiagnosed infections and maximizing the proportion of successfully treated persons living with HIV is still likely to further improve control of the epidemic. This is not a clinical trial.
The Paget disease represents a form of adenocarcinoma arising in epidermis; it can be distinguished in mammary (when involves the nipple areolar epidermis) and extramammary Paget disease (uncommon form that involves apocrine gland-rich areas); they present significant diagnostic challenges because of its nonspecific clinical appearance and frequent misidentification as benign, inflammatory skin conditions. Line-field confocal optical coherence tomography (LC-OCT) is a novel, noninvasive imaging modality that enables in vivo, real-time visualization of the skin with near-histological resolution. The objective of this study was to evaluate the diagnostic performance and clinical applicability of LC-OCT as a noninvasive imaging tool for the in vivo assessment of both mammary and extramammary Paget disease, and to establish their correspondence with conventional histopathological findings. This retrospective study included 4 patients with histopathologically confirmed diagnoses of mammary and extramammary Paget disease. All lesions were imaged in vivo with LC-OCT before biopsy. In both mammary Paget disease and extramammary Paget disease, LC-OCT identified intraepidermal clusters and single hypo-reflective Paget cells correlating with histological findings. LC-OCT represents a valuable adjunct in dermatologic diagnostics, offering near-histological, real-time visualization of cutaneous architecture. It can enhance diagnostic accuracy, guide biopsy site selection, improve preoperative margin assessment, and support follow-up after nonsurgical therapy.
Atopic dermatitis (AD) is a leading dermatological condition presenting in children and adolescents. Nearly one-fifth of children globally are diagnosed with AD, with higher prevalence and increased disease burden observed among racial minority groups, particularly children of African and Asian descent. Systemic therapies are a key component of managing moderate-to-severe atopic dermatitis; however, their safety and efficacy profiles may vary among pediatric patients with skin of color due to differences in disease phenotype, immune response, and underrepresentation in clinical trials. We aimed to investigate the literature for ethnic and racial representation of pediatric patients with AD in clinical trials of advanced systemic therapies. A rapid review was conducted, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 16 studies representing 21 clinical trials and 3148 patients were included. White patients represented over half of the total participant population investigated across all studies. Asian and Black demographics were the least represented at 16.7% and 9.4%, respectively. None of the clinical trials that were analyzed conducted a subset analysis of therapy outcomes for racial and/or ethnic variability. Although Black and Asian populations are disproportionately affected by atopic dermatitis, our review provides strong evidence of their continued underrepresentation in pediatric dermatological AD clinical trials. Adequate representation may be achieved by addressing frequent barriers, including mistrust in healthcare research, language barriers, lack of trial awareness, and logistical challenges of clinical trial participation.
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Atherosclerotic plaque rupture is a major cause of cerebrovascular events, yet the molecular determinants underlying vulnerability-related plaque morphology, including fibrous-cap thickness, remain incompletely defined. Using histomorphology-guided spatial proteomics, here we delineate molecular programs associated with plaque cap phenotype across discrete plaque subregions. In 112 carotid endarterectomy specimens, differences between thin-cap and thick-cap plaques were predominantly localized to the necrotic core and fibrous cap. These differences were enriched for processes related to inflammation, lipid handling, extracellular matrix remodeling and ossification/calcification, and supported the presence of proteome-based plaque subtypes. PCSK9 was among the proteins most strongly associated with thin-cap plaques. Consistently, an in vitro model of necrotic core-like oxidative and inflammatory stress increased PCSK9 secretion in primary vascular smooth muscle cells. Together, these findings localize molecular programs associated with cap phenotype to plaque compartments and provide a framework for spatially informed biomarker discovery in advanced carotid atherosclerosis.
Pyoderma gangrenosum (PG) is an ulcerative inflammatory dermatosis that is poorly characterised from a diagnostic and therapeutic perspective. We evaluated the clinical characteristics and healing outcomes in patients with PG according to ulcer size. We reviewed the medical records of patients with PG presenting to a tertiary hospital in Melbourne, Australia, from 20 December 2011 to 11 June 2024. We collected data on demographics, clinical characteristics, and classified cases into small (< 64 cm2) or large ulcers (≥ 64 cm2 or any tendon or muscle on view) according to the size of the largest ulcer during the treatment course. Healing outcomes assessed included rates of initial healing, healing time, recurrence rate, healing after recurrence, level of systemic treatment required, and mortality. 81 cases of PG were identified, including 38 (46.9%) small and 43 (53.1%) large ulcers. Large ulcers were associated with a history of multiple ulcers, peripheral vascular disease, and higher rates of advanced treatment (biologic or intravenous immunoglobulin therapy). After adjusting for age, sex, and peripheral vascular disease, large ulcers remained independently associated with lower rates of initial healing, higher rates of recurrence, lower rates of healing after recurrence, and longer healing times (all p < 0.05). Ulcer size was not associated with age, sex, ulcer location, tissue pathergy, inflammatory bowel disease, haematological malignancy, inflammatory arthritis, or diabetes mellitus. PG is a highly morbid condition that is slow to heal and frequently recurs. Ulcer size is an important predictor of healing outcomes. It is thus a meaningful way of stratifying patients and may provide useful prognostic information regarding the expected disease course.
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To evaluate the efficacy and safety of Q-switched 1064 nm fractional laser combined with intradermal tranexamic acid (TXA) injection in the treatment of melasma. This retrospective study initially reviewed 161 female patients with melasma who received laser therapy alone (group A), intradermal TXA injection alone (group B), and combination therapy (group C). After eligibility screening and 1:1:1 propensity score matching, 90 patients were included in the final matched analysis, with 30 patients in each group. Clinical outcomes were assessed using the Melasma Area and Severity Index (MASI), VISIA-derived ultraviolet and brown spot indices, and patient satisfaction. Adverse events and recurrence at 6 months were also evaluated. All groups demonstrated significant improvements in MASI scores and VISIA parameters (all P < 0.001). The combination group achieved significantly greater reductions in MASI scores and pigmentation indices compared with the other groups (all P < 0.001), along with a higher likelihood of patient satisfaction (OR = 3.82, 95% CI: 1.15-12.69, P = 0.028). Recurrence rates at 6 months were not significantly different among groups (P = 0.31), although numerically lower in the combination group. All treatments were well tolerated, with only mild and transient adverse events. Q-switched 1064 nm fractional laser combined with intradermal TXA injection was associated with greater clinical improvement and higher patient satisfaction compared with monotherapies. Melasma is a common skin condition that causes dark patches on the face. It can be difficult to treat, and the condition often returns after therapy. Many patients do not achieve satisfactory results with a single treatment, so better approaches are needed. In this study, we examined whether combining two treatments could improve outcomes. We reviewed the records of 161 women with melasma who received one of three treatments: laser therapy, small injections of tranexamic acid (a medication that reduces pigment formation), or a combination of both. After eligibility screening and statistical matching, 90 women were included in the final analysis. We assessed changes in skin pigmentation using clinical scoring, imaging analysis, and patient-reported satisfaction. All treatments led to visible improvement. However, the combination treatment produced greater reductions in pigmentation and higher patient satisfaction than either treatment alone. The treatments were well tolerated, with only mild and temporary side effects. While melasma can recur, we did not observe a significant difference in recurrence rates between groups over six months, although the combination group showed a trend toward lower recurrence. These results suggest that combining laser therapy with tranexamic acid injections may provide a more effective option for managing melasma, with good safety and improved patient outcomes.
Gestational diabetes mellitus (GDM) is an increasingly important public health problem associated with adverse maternal and fetal outcomes. The burden of GDM is rising in South Asia, including Bangladesh, yet data from tertiary care settings remain limited. To determine the prevalence of gestational diabetes mellitus and identify its associated risk factors among pregnant women attending a tertiary care hospital in Bangladesh. This hospital-based analytical cross-sectional study was conducted from January to June 2025 among pregnant women attending antenatal clinics at a tertiary care hospital in Bangladesh. A consecutive sampling technique was used, and 650 eligible pregnant women undergoing oral glucose tolerance testing (OGTT) were enrolled. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Sociodemographic, anthropometric, clinical, and obstetric variables were collected using structured interviews and medical records. Independent-samples t-tests, chi-square tests, and multivariable logistic regression analyses were performed using SPSS version 23. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were calculated. Women with GDM were significantly older and had higher obesity prevalence and BMI compared with non-GDM women. Family history of diabetes, polycystic ovary syndrome (PCOS), previous delivery of a baby weighing > 3.5 kg, and history of eclampsia were significantly associated with GDM. Multivariable logistic regression identified increasing maternal age, family history of diabetes, and PCOS as independent predictors of GDM. GDM is highly prevalent among pregnant women attending tertiary care facilities in Bangladesh. Advanced maternal age, positive family history of diabetes, and PCOS are important independent predictors. Early risk-based screening and preventive interventions may help reduce maternal and fetal complications associated with GDM.
To explore the clinical relevance of mitochondrial DNA (mtDNA) in systemic sclerosis (SSc) and elucidate the mechanism by which mtDNA leakage drives fibroblast activation. Plasma mtDNA was quantified by qPCR in 50 patients with SSc and 20 healthy controls (HC). Primary dermal fibroblasts from 5 diffuse cutaneous SSc (dcSSc) and 5 HC (n= 5 per group) were analyzed for mitochondrial structure, function and RNA-seq profiling. The opening of mitochondrial permeability transition pore (mPTP) and oligomerization of VDAC1 were examined with Ca2+ modulators and inhibitors. STING knockdown (siRNA) was performed for validation. The STING inhibitor H-151 was evaluated in vitro and in a bleomycin-induced skin fibrosis model (n= 6 mice per group). Plasma mtDNA levels were significanly higher in SSc than in HC, negatively correlating with forced vital capacity (FVC)% (r = -0.436, P < 0.01) , and correlating with modified Rodnan skin score (mRSS) ( r = 0.807, P < 0.001 ), IL-6 ( r = 0.667, P < 0.001 ) and TGF-β ( r = 0.678, P < 0.001 ). SSc fibroblasts exhibited abnormal mitochondrial morphology and dysfunction. Increased MCU and VDAC1 promoted mitochondrial Ca2+ overload, mPTP opening, VDAC1 oligomerization, cytosolic mtDNA accumulation, which activated the cGAS-STING pathway and triggered profibrotic responses. Pharmacologic blockade of mPTP or VDAC1 reduced cytosolic mtDNA, while H-151 suppressed profibrotic markers in SSc fibroblasts and attenuated dermal thickening and collagen deposition in bleomycin-treated mice. The Ca2+-mtDNA-cGAS/STING axis drives fibroblast activation and skin fibrosis in SSc, representing a promising therapeutic target.
Limited research explores dermoscopy use among physician associates (PAs), outside of one prior study examining dermoscopy in PA student education. This study sought to investigate dermoscopy use among practicing PAs and its impact on their overall diagnostic confidence, including in darker skin tones, when differentiating between benign and malignant skin lesions. An anonymous survey was developed in 2023 with input from experts in dermoscopy and survey creation to assess PA confidence in skin lesion evaluation as well as PA dermoscopy knowledge and use, perceptions, barriers to use, and prior education. The dermoscopy survey was included as an optional module in the 2024 American Academy of Physician Associates (AAPA) Salary Survey. Of 3174 invited PAs, 995 (31.4%) responded. Most had never used dermoscopy in practice (81%) but knew or recognized the term (71%). A majority (53%) believed PAs should be trained in dermoscopy during PA school, and 26% reported no interest in future dermoscopy use. Dermatology PAs reported more frequent dermoscopy use and generally greater confidence in evaluating skin lesions, both overall and in darker skin tones, than PAs in other specialties. PAs in surgical (OR = 0.2, 95% CI 0.1-0.6) and medical (OR = 0.3, 95% CI 0.2-0.5) subspecialties were less likely to use dermoscopy at least annually compared with PAs in primary care. PAs in rural areas were more likely to feel confident in differentiating skin lesions than those in urban areas (OR 2.9, 95% CI 1.7-5.0). Dermoscopy use is associated with higher overall skin lesion assessment confidence. Wider adoption, especially outside dermatology, requires training, increased advocacy, and expanded education.
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