Neuropsychological (NP) tests are multi-domain in execution. Reliance on a single score representing specific domains obscures the detection of subtle cognitive changes and increases risk of inaccurate assessment. Rooted in the Boston Process Approach (BPA), the Framingham Heart Study (FHS) captures multi-dimensional errors and process features within and across NP tests. We examined these BPA variables in community-dwelling older adults. We analyzed data from 2363 dementia-free participants aged 60 and above. Exploratory and confirmatory factor analyses used Kemeny covariance structures. Measurement invariance was estimated across age, sex, and education groups. We assessed the impact of demographics on latent factors, and the ability of these factors to predict future conversion to all-cause dementia. We trained machine learning (ML) models to compare NP and BPA data. Participants were older adults (mean age 71.5 ± 8.7 years), primarily female (54.2%), and non-Hispanic White (96.5%). The bifactor model was the only model with adequate fit (CFI = 0.96, RMSEA = 0.03). General and specific factors captured ability for accurate and strategic responses, test-specific variance, and nuanced executive and semantic processes distributed across tests. Higher general ability and stronger verbatim story recall were associated with a reduced likelihood of developing all-cause dementia (general: OR = 0.15, 95% CI [0.12-0.86]; recall: OR = 0.24, 95% CI [0.23-0.90]) over a median of 5.2 years. With NP/BPA data, ML models identified >99% of 222 converters. This study highlights the strengths of NP/BPA data. Multidimensional cognitive features may enhance sensitivity to early changes predictive of incipient dementia.
We evaluated a Remote Surgical Training model (ReST) in which the tutor operates a second da Vinci Xi console from an adjacent room while preserving integrated audio and the ability to take over control. A comparative feasibility study was conducted at RAIN (A. Cardarelli Hospital, Naples, Italy) between March 2021 and April 2023 using a porcine model. Thirty training sessions were analysed (15 ReST, 15 in-room dual-console controls). Trainee performance was assessed with the Global Evaluative Assessment of Robotic Skills (GEARS); post-session surveys captured perceptions, tutor-trainee agreement (weighted Cohen’s κ), priority rankings (Kemeny aggregation with τX) and satisfaction. GEARS internal consistency was acceptable (Cronbach’s α overall 0.805; control 0.837; ReST 0.768). No statistically significant differences were observed for the GEARS total score (Mann-Whitney U = 105, p = 0.595) or domains (p = 0.074–0.683). Tutor-trainee agreement was significant for three interaction items: ease of teaching/training (p = 0.004), ability to follow the trainee’s actions (p = 0.011) and overall interaction quality (p = 0.014). Priority rankings in both roles emphasised clarity of instruction and takeover capability, while physical proximity ranked lowest. Tutors and trainers reported high satisfaction in both groups; one trainee reported low satisfaction in the ReST group. Adjacent-room ReST with takeover capability was feasible in this porcine-model training setting and showed no observed performance decrement compared with conventional in-room dual-console training. These findings should not be interpreted as proof of equivalence or as validation of true long-distance teleproctoring; further work is required for larger samples, participant-level baseline adjustment, and longer-distance configurations.
Inter-basin water diversion projects are crucial for mitigating the spatial imbalance between water supply and demand. However, their operation is challenged by complex uncertainties arising from climate variability and hydrological fluctuations. To address these challenges, this study develops a multi-objective risk operation model and decision-making model for inter-basin water diversion projects. At the operational level, a multi-objective risk operation model is formulated to minimize both the total water shortage in water-receiving regions and the total transfer cost at pumping stations, while explicitly accounting for forecast uncertainties in source water availability. The model is solved by the Multi-Objective Mantis Search Algorithm (MOMSA) to generate a set of non-dominated solutions. At the decision level, a comprehensive risk decision-making model is established by integrating the Kemeny Median Indicator Ranks Accordance (KEMIRA) framework with the Best-Worst Method (BWM) for expert input and Data Envelopment Analysis (DEA) for dynamic weighting. The proposed framework is applied to the "One Gate Three Lines " project, a major water diversion project in China. The results show that non-dominated solutions under uncertainties effectively encompass the deterministic solution space. Compared with the deterministic case, the average water shortage rate reduces by 1.92 %, while the average transfer cost increased by CNY 63,300 due to uncertainty considerations. The risk decision-making model effectively captures multiscale risks and supports adaptive, risk-informed decision making for inter-basin water diversion operations under climate variability.
Hepatic artery infusion pump chemotherapy (HAIC) improves colorectal liver metastasis (CRLM) outcomes, but treatment-associated biliary sclerosis (BS) is a major complication. This study evaluates the incidence of and risk factors for BS after HAIC for CRLM. This was a single-center retrospective analysis including all patients with CRLM treated with floxuridine between 2000 and 2022. The primary outcome was BS, intractable hyperbilirubinemia, and/or biliary stricture not caused by cancer progression requiring percutaneous or endoscopic stenting or drainage. BS was analyzed using competing risk methods where death was the competing event. Between 2000 and 2022, a total of 2239 patients received HAIC for CRLM, 48% (n=1067) received adjuvant HAIC and 52% (n=1172) were unresectable. There were 128 (6% at 60 months) BS events, and rates did not differ between adjuvant (n=66) and unresectable (n=62) groups (60-month estimate: 6% [95% confidence interval (CI) 5-8] vs 6% [95% CI 4-7]; p=0.362). Operative variables, variant hepatic arterial anatomy, non-gastroduodenal artery cannulation, and extrahepatic perfusion were not associated with BS. In adjuvant cases, BS risk increased with each cycle (hazard ratio [HR] 1.123, p=0.003) and every 100 mg of cumulative floxuridine (HR 1.087, p<0.001) controlling for concurrent colorectal resection and variant vessel ligation. Among unresectable patients, each cycle (HR 1.087, p<0.001) and every 100 mg of cumulative floxuridine (HR 1.054, p<0.001) increased BS risk, controlling for race and concurrent colorectal resection. The incidence of BS after HAIC for CRLM is 6% after 60 months and does not differ in the adjuvant and unresectable setting due to meaningful differences in survival. Cumulative floxuridine dose and number of HAIC cycles were independently associated with increased BS risk.
To assess the proportion of unresectable colorectal liver metastasis (CRLM) patients meeting liver transplant (LT) criteria and define their outcomes following hepatic artery infusion pump (HAIP) chemotherapy. The TransMet RCT demonstrates improved survival with combined LT and systemic versus systemic therapy alone; however, systemic therapy might not be the best control. This study assesses outcomes in similarly selected patients treated with HAIP. We identified unresectable CRLM patients treated with HAIP between 2006-2016. Modified TransMet/SECA-II selection criteria were applied, including pre-treatment with at least 1st line chemotherapy before HAIP placement. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier methods from HAIP placement. Of 483 patients identified, 23 (4.8%) were LT-eligible. Median age was 52 years (range:37,73). Primary tumors were right-sided in 6 (23%) and rectal in 12 (52%). Eight (38%) patients were KRASmut. Median CRLM size and number were 28 mm (range:9,92) and 11 (range:4,38). Median pre-HAIP chemotherapy cycles were 8 (range:3,20), and most patients were on 1st (15,65%) or 2nd (7,30%) line therapy. Conversion to resection occurred in 18 (78%) patients after a median of 5 (range:1,20) HAIP chemotherapy cycles. With a median follow-up time of 98 (95%CI:96,NR) months, median OS was 61 (95%CI:36,92) months, and 5-year OS was 53% (95%CI:36,79). Median PFS was 13 (95%CI:10,22) months. In this cohort, less than 5% of unresectable CRLM patients were LT-eligible. After treatment with HAIP chemotherapy, overall 5-year survival was 53%, similar to a recent LT randomized trial (5-year OS 57%).
In an era of antimicrobial resistance (AMR), identifying alternatives to conventional antibiotics in livestock farming is vital for veterinary medicine and public health. Due to the constant exposure to pathogens and the need for optimal productivity, maintaining gut homeostasis is essential in poultry. Therefore, investigating antimicrobial alternatives that can support gut health is of key importance. Host defense peptides (HDPs) have been identified as promising candidates due to their beneficial effects on the gut; however, there is still much to clarify regarding the individual peptides' mechanism of action. In the present study, the HDP cecropin A (CecA) was applied to chicken-derived ex vivo ileal explant cultures to examine its impact on immune response and tight junction (TJ) protein expression. CecA was applied at 3.125 and 6.25 µg/mL concentrations, either alone (Cec-low and Cec-high) or in polyinosinic-polycytidylic acid (Poly I:C, 50 µg/mL)-induced inflammatory conditions (PI:C + Cec-low and PI:C + Cec-high). The experiment revealed that CecA had no impact on cell viability, as reflected by unchanged metabolic activity and extracellular lactate dehydrogenase activity. Regarding the immune state, Cec-high and PI:C + Cec-high increased the production of interleukin (IL)-2, whereas IL-6 concentration was decreased by PI:C + Cec-low treatment. Furthermore, Cec-high elevated the intracellular expression of the TJ protein claudin-3. In conclusion, CecA displayed immunomodulatory activity in chicken intestinal cells and supported epithelial integrity without exerting cytotoxic effects.
The role of tumor-infiltrating B cells (TIL-Bs) in shaping anti-tumor responses in the context of immune checkpoint blockade remains incompletely understood. Here, we interrogate the humoral response in resected lung tumors from patients with non-small cell lung cancer (NSCLC) treated with neoadjuvant PD-1 blockade. We find that tumors orchestrate tertiary lymphoid structures with CD138+ plasma cells, from which we clone recombinant monoclonal antibodies (mAbs) using B cell receptors (BCRs) exhibiting somatic hypermutation and class switching. Several mAbs bind cell-surface citrullinated proteins, characteristic of cancer cells. Chimeric antigen receptor (CAR) T redirected with the soluble chain fragment variable (scFv) of our lead candidate antibody (PC-1) specifically target tumor cells and tumor-promoting myeloid cells in vivo without off-target activity. Moreover, ablation of the citrullination enzyme PADI2 in tumor-bearing mice eliminates reactivity to PC-1 and cytotoxic killing by the CAR. Our results implicate a therapeutic potential for tumor-infiltrating plasma cells that may be harnessed for cancer treatment.
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The association between moderate-to-severe psoriasis and cardiovascular (CV) risk is well known. No clear link between disease activity, disease duration, and CV risk has been established thus far to identify high CV risk patients with psoriasis without CV symptoms. We aimed to investigate the relationship between moderate-to-severe psoriasis and cardiovascular disease (CVD) by introducing and determining the cutoff value for a new tool, the cumulative duration of severe psoriasis (CDSP), reflecting the total duration of severe psoriasis skin symptoms. Ninety-eight asymptomatic patients with moderate-to-severe psoriasis were enrolled in this cross-sectional study, without cardiac symptoms. CDSP was recorded using a structured questionnaire. CDSP threshold, defined as Coronary Artery Calcium Score (CACS) > 0, was determined using receiver operating characteristic curve analysis. Ultrasound (intima-media thickness (IMT) and carotid, brachial, and femoral artery plaque burden) and cardiac computed tomography (CACS, segment involvement score (SIS), and coronary artery disease-reporting and data system severity (CAD-RADS™)) were performed. Controls (n = 248) were matched for age, sex, body mass index, and, where possible, comorbidities. CACS was significantly higher in psoriasis (mean 159.02, standard deviation 365.60) compared to controls (73.12, 166.08), P = 0.029. The CDSP threshold was 60.5 months. Patients with long-CDSP (> 60.5 months) had significantly higher CACS (214.63, 430.11) than patients with short-CDSP (57.61, 162.53), P = 0.012. SIS and CAD-RADS were also significantly higher in the long-CDSP group compared to the short-CDSP group (4.50, 3.85 vs. 1.39, 2.06), P = 0.002 and (2.06, 1.63 vs. 0.71, 1.08), P = 0.003, respectively. Patients with long-CDSP showed a non-significant trend towards higher IMT and peripheral plaque burden. Patients with long-CDSP had a greater extent and severity of CVD. This innovative predictor is easily determined by dermatologists and assists in the early identification of asymptomatic high CV risk patients with psoriasis. Graphical abstract available for this article. Psoriasis is a common skin disease characterized by inflammation, resulting in itchy, red, and scaly skin lesions. The inflammation also affects the blood vessels. Therefore, patients with severe psoriasis have a higher risk of cardiovascular disease, which affects the heart and blood vessels. We propose that patients with longer periods of severe psoriasis are exposed to inflammation for longer and, consequently, are at a higher risk of cardiovascular disease than those with shorter durations of severe symptoms. This study, conducted in Hungary, aimed to investigate the relationship between cumulative duration of severe psoriasis and cardiovascular disease by performing highly sensitive heart scans and ultrasound of blood vessels. Ninety-eight patients with psoriasis were included and matched with non-psoriasis controls. Our findings showed that patients with psoriasis had a greater cardiovascular disease burden, as assessed by imaging tests. Furthermore, patients with long cumulative duration of severe psoriasis (> 60.5 months) had a greater extent and severity of cardiovascular disease than patients with short cumulative duration of severe psoriasis. In conclusion, patients with a long cumulative duration of severe psoriasis are at higher risk of cardiovascular disease. Dermatologists play a vital role in the early identification of asymptomatic high cardiovascular risk patients with psoriasis and referring them to cardiology in order to prevent potentially life-threatening complications, such as heart attacks.
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Noninvasive imaging techniques are playing an increasingly significant role in dermatologic diagnosis, risk evaluation, and the monitoring of therapeutic outcomes. In the August issue of the Journal, we highlight how dermoscopy, onychoscopy, trichoscopy, and line-field confocal optical coherence tomography (LC-OCT) can refine clinical decision-making across acral melanocytic lesions, onycholysis, primary cicatricial alopecia, and hyperkeratotic actinic keratoses. These papers show that imaging is most useful when tailored to anatomical and clinical context, advancing standardized and clinically actionable imaging approaches.
Major advances have broadened the therapeutic landscape of inflammatory skin diseases. In psoriasis, alongside the tyrosine kinase 2 (TYK2) inhibitor deucravacitinib, the United States Food and Drug Administration (FDA) has approved the first oral interleukin-23 (IL-23) receptor antagonist peptide, icotrokinra. In atopic dermatitis, new data have emerged on stapokibart, an interleukin-4 receptor alpha subunit (IL-4Rα) inhibitor introduced in China. In hidradenitis suppurativa, glucagon-like peptide-1 receptor agonists (GLP-1 RA) are also gaining increasing attention as adjunctive therapy.
This study aimed to assess aspects of validity of four FACE-Q Aesthetics scales in a sample of patients undergoing and planning facial minimally invasive cosmetic procedures (MICPs), such as botulinum toxin, lip augmentation and soft tissue augmentation treatments. In 2023, a cross-sectional survey included 210 Hungarian women who had undergone and 147 planning facial MICPs, with similar mean ages Respondents completed four FACE-Q scales (Aging Appraisal, Appearance Distress, Early Life Impact and Age VAS), EQ-5D-5L, Rosenberg Self-Esteem Scale (RSES) and the Brief Fear of Negative Evaluation Scale-Straightforward Items (BFNE-S). Comprehensibility, ceiling/floor effects, structural validity (principal component analysis, confirmatory factor analysis), internal consistency, and construct validity (convergent, divergent, known-group validity) of the four FACE-Q scales were assessed. All FACE-Q scales, except the Age VAS, showed a ceiling effect (20-28%). Appearance Distress showed strong convergent validity with RSES (r = 0.742), BFNE-S (r = - 0.702), and EQ-5D-5L anxiety/depression (r = - 0.519). Aging Appraisal and Appearance Distress scales were unidimensional, whereas Early Life Impact Scale had a three-factor structure. All four FACE-Q scales were able to differentiate between known groups of patients based on self-esteem, fear of negative evaluation and acceptance of bodily appearance. Women who had undergone procedures reported higher Aging Appraisal (72.9 vs. 63.3) and Appearance Distress (77.1 vs. 68.4) scores and felt younger (- 5.0 vs. - 2.8 years) than those planning them (p < 0.001 for all). Our findings provide initial support for the validity of the four FACE-Q scales in MICP populations, but further validation (e.g. assessment of responsiveness and test-retest reliability) is needed.
The reduction of antibiotic use in livestock production necessitates the development of reliable in vitro models for evaluating alternative immunomodulatory compounds. In this study, porcine hepatocyte-non-parenchymal (NP) cell co-cultures and small intestinal explants exposed to pathogen-associated molecular patterns (PAMPs), including lipopolysaccharide (LPS), lipoteichoic acid (LTA), flagellin and polyinosinic-polycytidylic acid (poly I:C), were established as inflammatory models. Hepatic co-cultures exhibited pronounced inflammatory responses, with LPS and LTA increasing hepatocellular interleukin (IL)-4, IL-6, IL-8 and tumor necrosis factor (TNF)-α release, alongside elevated extracellular lactate dehydrogenase activity and maintained metabolic activity, indicating membrane perturbation without marked cytotoxicity. Poly I:C was found to be cytotoxic, accompanied by an altered cytokine profile. All PAMPs enhanced reactive oxygen species production without remarkable lipid peroxidation in most cases. In contrast, intestinal explants showed high resilience with unchanged viability and limited cytokine responses. Only IL-6 and IL-8 were detectable, with LPS elevating IL-8, while poly I:C and flagellin increased IL-6 levels. These findings demonstrate marked tissue-specific differences in inflammatory responsiveness. The hepatic co-culture model provides a sensitive system for studying robust inflammatory reactions, whereas intestinal explants are suitable for investigating moderate, gut-specific immune responses. In conclusion, these complementary models offer valuable tools for evaluating antibiotic alternatives in swine.
Janus kinase signal transducer and transcription activator (JAK-STAT) inhibitors have revolutionized the treatment of immune-mediated inflammatory diseases (IMIDs) of the skin, such as in atopic dermatitis, alopecia areata and vitiligo. Although several meta-analyses have confirmed their efficacy, concerns remain about the risk of infection, as the JAK-STAT pathway plays a key role in immune defence. Previous meta-analyses examined only selected, pre-specified infection categories and have not comprehensively evaluated all reported infection types or compared systemic and topical agents. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that reported infection-related adverse events in patients treated with systemic or topical JAK-STAT inhibitors for IMIDs of the skin. The study followed the PRISMA 2020 and Cochrane guidelines (PROSPERO: CRD 42024615839). Overall risk ratios (RRs) with 95% confidence intervals (CI) were calculated using a random-effects model. Seventy-four RCTs were included, involving more than 29,000 patients. JAK-STAT inhibitors were associated with an increased risk of influenza (RR = 2.12, 95% CI 1.03-4.36), bronchitis (RR = 2.03, 95% CI 1.43-2.88) and herpes zoster (RR = 1.67, 95% CI 1.29-2.15) compared to a placebo. The risk was particularly elevated in patients with atopic dermatitis (influenza: 3.22, 95% CI 2.03-5.10, herpes zoster: RR = 2.00, 95% CI 1.34-2.99). No significant risks were identified for serious, fungal or opportunistic infections, and topical JAK-STAT inhibitors demonstrated a favourable safety profile comparable to vehicle controls. This meta-analysis provides a comprehensive assessment of the risk of infection associated with JAK-STAT inhibitors in IMIDs of the skin. Although overall safety is acceptable, clinicians should be aware of the higher infection risk of influenza and herpes zoster and should consider vaccination and preventive strategies for high-risk patients with atopic dermatitis. The main limitation is that the included studies involved highly selected populations with few comorbidities and short follow-up.
External insults can cause immune activation in immune cells, resulting in persistent molecular changes that can lead to innate immune memory changes in these cells. This study investigated the potential for cellular reprogramming in response to Cutibacterium acnes in keratinocytes. We exposed normal human epidermal keratinocytes (NHEKs) obtained by mammoplasty (denoted as NHEK-B) or abdominoplasty (denoted as NHEK-A) to C acnes, followed by stimulation with Pam3CSK4 to assess immune activation and cellular responses. In NHEK-B cells, C acnes and Pam3CSK4 treatment induced trained immunity-type responses, higher expression of selected immune target genes, and a diminished response compared with trained and Pam3CSK4-induced NHEK-A cells. Total transcriptome analysis delineated regional differences, with the activation of immune-related pathways in NHEK-B cells and alterations in keratinocyte differentiation processes in NHEK-A cells. We detected differences in metabolic regulation, and utilizing pharmacological inhibitors, we demonstrated the necessity of the optimal regulation of histone acetylation and DNA methylation for the changes mentioned earlier. This study demonstrated that C acnes triggers innate immune memory processes in keratinocytes, characterized by signaling, epigenetic, and metabolic reprogramming that influences cellular responses to subsequent stimuli. The observation that analogous insults might elicit skin region-specific responses offers insights into the etiology and mechanisms underlying common inflammatory skin diseases.
Psychodermatology, adolescent mental health, quality-of-life measurement, financial toxicity, and teledermatology all show how dermatology increasingly extends beyond visible lesions. The September issue of the Journal addresses the psychological complexity of aesthetic and medical consultations, the psychiatric burden of atopic dermatitis in adolescence, limitations of a commonly used quality-of-life measurement, the financial toxicity experienced by patients with hidradenitis suppurativa, and the still uneven implementation of teledermatology and teledermoscopy in Europe. Together, these papers emphasize that high-quality dermatologic care requires clear communication, mental-health consideration, valid patient feedback, awareness of costs, and robust digital support.
Objectives: Obesity and the associated metabolic dysfunction influence fertility performance at molecular levels and ABC transporters are considered as potential molecular factors affecting fertility both in the testis and sperm; therefore, we aimed to examine the effect of a short-term diet-induced obesity on testicular and spermatic ABC transporters in a rat model focusing on the expressions of P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (BCRP, Abcg2). The testicular androgen state involving aromatase enzyme (Cyp19a1), androgen receptor (Ar), and testosterone levels were also evaluated. Methods: Obesity was induced in male Sprague Dawley rats by feeding a high-fat, high-sugar diet (HFHSD) for 10 weeks, and metabolic status was evaluated using a glucose tolerance test. The weight and size of reproductive organs were measured, and Abcb1a/1b, Abcg2, Cyp19a1, and Ar expression in testes or sperm was determined by RT-PCR and Western blotting. At the same time, testosterone levels were measured by ELISA. Results: HFHSD successfully induced higher weight gain with glucose intolerance and reduced reproductive organ size. In obese rats, testicular Abcb1a and Abcb1b mRNA and P-gp protein expression were significantly higher, whereas testicular Abcg2 mRNA levels decreased. Spermatic Abcb1a, Abcb1b and Abcg2 mRNA expression also reduced in obesity. Neither testicular testosterone concentration nor Cyp19a1 and Ar mRNA expression levels changed after the 10-week obesogenic diet compared with controls. Conclusions: Overall, our study revealed infertility-related ABC transporter changes in obese male rats, suggesting that these alterations may predispose obese males to fertility impairments, even before the obesity-induced androgen dysregulation.
Preoperative hepatic artery infusion pump chemotherapy (HAIP) in colorectal liver metastases (CRLM) is associated with greater pathologic response (PR). We aimed to identify genomic predictors of PR in initially unresectable (IU)-CRLM treated with preoperative HAIP. Three-hundred-fifty patients treated with HAIP for IU-CRLM from 2000 to 2021 were reviewed retrospectively; 96 underwent resection. Specimens were evaluated for PR and next-generation sequencing was performed. Wilcoxon rank-sum test was used to determine the association between genomic alterations and PR (continuous outcome). PR was categorized as minor (0%-74%), major (75%-99%), and complete (100%). Association between co-mutation TP53-RAS and PR was assessed using multivariable linear regression. Cox regression was used to examine the association between PR and survival. Median PR was 51% in patients with TP53-RAS; 91% in those without the co-mutation (Others) (P < 0.001). TP53-RAS remained associated with lower PR (β -0.25, P < 0.001) on multivariate analysis. PR was associated with event-free survival (EFS) (HR 0.92, 95% CI: 0.85-0.98; P 0.013), not with overall survival (OS) (HR 0.94, 95% CI: 0.86-1.03). TP53-RAS in IU-CRLM is associated with lower rates of PR to preoperative HAIP than Others. PR was associated with EFS, not with OS.
The February issue of the IJD reflects the growing complexity of managing chronic inflammatory skin diseases in the era of targeted therapies. Covering atopic dermatitis, psoriasis, and hidradenitis suppurativa, the featured papers address clinically relevant questions related to treatment safety, disease-associated comorbidities, and long-term therapeutic outcomes. Key topics include vaccination strategies in patients receiving Janus kinase inhibitors, ocular complications associated with atopic dermatitis, malignancy considerations in biologic-treated psoriasis, long-term efficacy and safety of selective tyrosine kinase 2 (TYK2) inhibition, and dose optimization of biologic therapy in hidradenitis suppurativa. Together, these contributions highlight a shift toward personalized, risk-aware management strategies that balance sustained efficacy with long-term safety in chronic inflammatory dermatoses.