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Specific (leukemia cutis) and nonspecific (reactive or secondary) skin lesions are associated with systemic leukemia. The following categories of leukemia cutis are discussed in this article: myelogenous (granulocytic) leukemia, monocytic leukemia, myelomonocytic leukemia, lymphocytic and lymphoblastic leukemia, hairy cell leukemia, and adult T-cell leukemia/lymphoma. The temporal relationship between the diagnoses of systemic leukemia and leukemia cutis, the course, and the prognosis are also discussed. Other sites of extramedullary involvement are correlated with leukemia cutis. The appearance of specific skin lesions in leukemia is usually associated with a very poor prognosis.
Primary systemic amyloidosis (PSA), also referred to as amyloid light-chain (AL) amyloidosis, is characterized by the deposition of insoluble monoclonal immunoglobulin light chains or L-chain fragments in a variety of tissues and organs of the body. There is a dearth of literature regarding the mucocutaneous manifestations of PSA in the Indian population, which prompted us to undertake the present study. We aimed to study the clinical characteristics of mucocutaneous manifestations in patients with PSA at a tertiary care center in Kolkata. Consecutive patients with PSA, who presented to our facility with cutaneous features were included in this cross-sectional observational study done over 4 years. The study involved 14 patients diagnosed with systemic amyloidosis (PSA) presenting with mucocutaneous symptoms. The mean age at diagnosis was 62.8 years, with a female-to-male ratio of 2:5. Myeloma-associated primary amyloidosis was identified in 35.7%. All patients showed pinch purpura, macroglossia, and tongue ridging. Periorbital purpura was seen in 92.8%, facial purpura in 85.7%, waxy nodules in 78.5%, xerosis in 57%, and diffuse alopecia in 35.7%. Relatively rare features included thickened skin, nail dystrophy, bullous lesions, lingual and subcutaneous nodules, atrophie blanche, and cutis laxa. Macular/lichen amyloidosis was also observed in one patient each. The head and neck were universally involved (100%). Eight patients had systemic features. The study was limited by its hospital-based design, small sample size, and lack of lesional biopsies. PSA has a wide gamut of cutaneous features, and recognizing these skin lesions in the setting of PSA may be a significant clinical indicator of the underlying systemic illness.
Ultraviolet A (UVA) radiation induces skin photoaging. The yeast Clavispora lusitaniae P8, isolated from the Turpan Basin, was studied as a potential source of novel natural anti-photoaging agents. This study aimed to analyze the composition of its fermented filtrate (P8) and investigate its protective effects and mechanism against UVA-induced damage in human skin cells. The chemical profile of P8 was analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS). Optimal UVA dose and a protective P8 concentration were determined by MTT assay. In HaCaT and HFF-1 cells, protective effects were evaluated by measuring markers including Lactate Dehydrogenase (LDH) release, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), cell migration, malondialdehyde (MDA), and antioxidant enzyme activities. P8 contained photoaging-related compounds (carboxylic acids and derivatives, organooxygen compounds, fatty acyls, and flavonoids) and significantly alleviated UVA-induced cellular damage by reducing oxidative stress markers, restoring mitochondrial function, promoting cell migration, increasing type I collagen levels, and suppressing matrix metalloproteinases expression. Transcriptomic and metabolomic analyses identified the Interleukin-17 (IL-17) signaling pathway as the key pathway. Western blotting confirmed that P8 inhibited UVA-induced activation of the IL-17 pathway, reducing expression of interleukin-17 receptor A (IL-17RA) and phosphorylated nuclear factor kappa B (p-NF-κB). Furthermore, using the IL-17 A neutralizing antibody Ixekizumab verified that the anti-photoaging effect is primarily mediated through the IL-17 A/NF-κB axis. This study is the first to link P8 with the inhibition of the IL-17/NF-κB axis, confirming its potential as a promising anti-photoaging candidate.
This review examines enhancements to the U-Net's ability to represent complex spatial structures for segmentation through attention mechanisms. The study surveys applications across both medical and non-medical domains, focusing on cSAM, cCAM, CBAM, and their associated serial (sfSCAM) and parallel (pfSCAM) fusion architectures. Beyond accuracy, the analysis also considers backbone design, diversity of evaluation metrics, pruning strategies, and potential sources of bias. Following PRISMA guidelines, we systematically searched major academic databases using U-Net- and attention-related keywords. The final corpus was constructed through stepwise exclusions (E1-E3) from an initial set of 1807 retrieved records. Spatial, channel, and hybrid attention modules were taxonomized; their placement within encoder, decoder, skip, and bottleneck blocks was identified; and application trends across domains such as liver, brain, skin, and retinal imaging were summarized. Attention-augmented U-Net models consistently improved the segmentation of subtle, scale-dependent structures across modalities, including CT, MRI, ultrasound, dermoscopy, fundus, and satellite imaging. Spatial attention in skip connections and decoders reduced noise while preserving boundaries, whereas encoder-level channel attention improved semantic weighting; CBAM combined both effects. Parallel fusion (pfSCAM) balanced accuracy and efficiency, while serial fusion (sfSCAM) enabled stable feature refinement. Attention placement strongly influenced global-local fusion and noise suppression. Pruning reduced computational cost with minimal performance loss, although evaluation remained focused on Dice and cross-entropy, with limited use of IoU, Hausdorff distance, and F1-score. Spatial and channel attention, along with their serial and parallel fusion variants, function as structural design principles within the U-Net. Effective practice integrates careful module placement, pruning or quantization strategies, and explicit bias auditing.
To introduce micro botulinum toxin therapy (MBT) for the treatment of aging skin, scarring, and other skin therapies. Mesotherapy involved the injection of microdoses of vitamins and nutrients, and serves as the backdrop for this current intervention. MBT is advocated to work on improving both epidermal and dermal damage through cellular repair induced by dilute botulinum toxin (BT). The technique does not require any sophisticated technology to perform other than a syringe loaded with dilute BT. Patients of all Fitzpatricks and ages are eligible for therapy without risk other than rare, temporary paresis. The technique involves injection of hyperdilute BT intradermally across the entire expanse of the face, neck, chest, etc., to effect desired skin changes. None. Other ingredients could be added to further enhance the efficacy of MBT. MBT offers unparalleled safety and efficacy in all skin types for a variety of skin improvements, including active acne, acne scarring, pores, texture, and generalized cutaneous sun damage and aging.
Despite considerable advances in nanotherapeutics, their clinical application is often limited by suboptimal monotherapy, rapid immune clearance and insufficient target-site accumulation. These limitations are particularly pronounced in the treatment of flap necrosis because of the complex ischemic microenvironment. To address this challenge, we fabricated a multifunctional therapeutic platform by loading melanin nanoparticles (MNPs) with the PI3Kα agonist UCL-TRO-1938, coating them with membranes derived from tert-butyl hydroperoxide (TBHP)-preconditioned human umbilical vein endothelial cells (HUVECs), and embedding them within a fibrin hydrogel. The resulting CM-1938@MNP hydrogels conferred cytoprotective effects in vitro by rescuing HUVECs from TBHP induced dysfunction and shifting macrophage polarization from the M1 to M2 phenotype. In a mouse model of ischemic skin flaps, local injection of the hydrogel markedly improved flap survival by stimulating angiogenesis, alleviating oxidative stress, and suppressing inflammation; these results were confirmed by RNA-seq analysis. This work presents a biomimetic strategy that transcends conventional single target therapies, offering a promising versatile platform for treating ischemia.
Cutaneous squamous cell carcinoma (cSCC) is a common and potentially aggressive skin cancer, with limited therapeutic options for advanced disease. The Hedgehog/GLI (HH/GLI) signaling pathway has emerged as a potential therapeutic target in cSCC. Itraconazole (ITZ), a repurposed antifungal agent, exhibited HH/GLI pathway inhibition but suffers from unfavorable physicochemical properties. Herein, we report the rational design and evaluation of truncated-ITZ analogues as novel HH/GLI pathway inhibitors for cSCC treatment. Starting from the metabolite-inspired lead compound A-26, two series of analogues were synthesized and optimized through structure-based drug design and ligand-lipophilicity efficiency-driven optimization. Among them, compound 16 demonstrated potent HH/GLI pathway inhibition and enhanced aqueous solubility. Compound 16 selectively inhibited proliferation of A431 SCC cells, suppressed colony formation, and induced cell apoptosis. In an A431 xenograft model, 16 significantly suppressed tumor growth with downregulation of GLI1, Ki67, and SOX2. Preliminary safety evaluation revealed no significant hematological or organ toxicity. These results established truncated-ITZ analogues as promising HH/GLI pathway inhibitors and support further development of compound 16 as a potential therapeutic agent for cSCC.
Despite decades of research and multiple phase 2b/3 trials, an effective HIV vaccine remains out of reach. A key obstacle is the need for innovative delivery strategies that can induce potent and durable protective immune responses. Targeting antigen-presenting cells in the skin, specifically Langerhans cells (LCs), offers a promising approach to enhance vaccine efficacy by promoting early and efficient activation of the humoral immune system. We developed an Antibody-Mediated targeting Vaccine (AMV) platform that delivers HIV-1 Env trimeric antigens directly to LCs via an anti-Langerin scFv domain. Two constructs were tested: LC3.Env3, carrying a trimeric gp140z Env fusion protein, and LC3.SOSIP, carrying the well-characterised BG505 SOSIP.664 trimer. Immunogenicity of these constructs was evaluated in mice and rabbits without adjuvant, assessing the germinal centre (GC)/Tfh reaction in draining lymph nodes (dLN), Env-IgG production and HIV-1 neutralisation. We show that, as compared to an anti-Langerin mAb fused with Env monochains, LC-targeted delivery of Env3 through LC3.Env3 significantly enhanced Tfh and GC B cells (BGC) formation (p < 0.0001), with an expansion of Env-specific BGC cells in mice (p < 0.05). Env IgG responses was enhanced with LC3.Env3 as compared to non-targeted trimeric Env (p < 0.05). Results were extended using LC3.SOSIP constructs which maintained the structural integrity of trimeric Env, but also markedly promoted as compared to Env3 and LC3Env3 the presentation of the native-like, prefusion-closed structure that displays all major quaternary-dependent broadly neutralising antibodies (bNAbs) regions. LC3.SOSIP elicited in rabbits robust, Env-specific antibody responses with cross-clade reactivity, including neutralising antibodies (NeutAbs), without the use of adjuvants. Finally, as compared to non-targeted SOSIP, LC3.SOSIP elicited stronger Env IgG responses (p < 0.01), even at low antigen doses, and neutralising activity against to Tier-1A but also autologous BG505 Tier-2 viruses (2 rabbits out of 8). These results validate LC-targeting as an efficient, adjuvant-free, strategy for inducing potent humoral responses against HIV-1. The AMV platform enables precise delivery of structurally intact Env trimers to skin-resident LCs facilitating early B cell activation and maturation. This approach offers distinct advantages over conventional adjuvanted sub-unit protein vaccines supporting its potential for clinical translation. This work was supported by Inserm, the Vaccine Research Institute (VRI), the French National Research Agency (ANR-10-LABX-77, ANR-10-INBS-05-02, ANR-10-EURE-0003), and the European Union's Horizon 2020 (grant 681032).
This study aimed to develop and content-validate a computerised clinical decision support system (CDSS) to support primary care clinicians in structured wound assessment and decision-making, by standardising assessment, guiding treatment planning, and reducing variability in practice. An adapted RAND/UCLA Appropriateness Method was applied to develop and assess the content validity of the CDSS. A panel of two clinical nurse specialists, one dermatologist, and one nursing professor constructed a clinical decision support tree based on evidence and guidelines, which was transformed into an interactive tool. Two validation rounds were conducted with wound care experts (n = 36 invited; 24 participated in round 1 and 22 in round 2), who evaluated the relevance, comprehensiveness, and clarity of each node using the item-level content validity index (I-CVI). The initial CDSS emphasized assessment of wound etiology, infection, wound bed, exudate, and wound edges. In round 1, most nodes achieved acceptable validity (I-CVI >0.78), and revisions improved infection assessment, wound classification, and exudate definitions. In round 2, all nodes met the I-CVI threshold, confirming strong content validity. The final CDSS, named WoundPilot, incorporated expert feedback, simplified navigation, and included supportive definitions, images, and referral guidance. WoundPilot provides a structured, holistic tool for wound management in primary care, offering a content-validated framework for structured wound assessment and decision-making. Clinical validation is required to evaluate its usability, reliability, integration with digital platforms, and performance in real-world settings. The system was designed for subsequent translation and international validation in comparable healthcare contexts.
Acne is a chronic inflammatory skin disease driven primarily by Propionibacterium acnes (P. acnes) colonization in hair follicles, which can progress from mild to severe forms and result in permanent scarring if left untreated. To resolve this problem, this study developed a polysaccharide-based light-heat-mediated soluble microneedle system for the transdermal delivery of antiacne agents encapsulated in mesoporous polydopamine nanoparticles (MPDA) for the effective treatment of acne vulgaris. A multifunctional microneedle (Cur-MPDA + Cur@HA/FPS MNs) based on hyaluronic acid and fucoidan (FPS) was prepared and functionalized by curcumin-loaded mesoporous polydopamine nanoparticles (Cur-MPDA) and backing containing curcumin, endowing it with a photothermal response, sustained-release, robust reactive oxygen species scavenging capacity, and antibacterial multiple properties. The microneedle system exhibited good mechanical strength and rapid tip dissolution within 2 min upon insertion. It demonstrated a strong antibacterial activity with 70.9% against P. acnes, good biocompatibility, and acne inflammation reduction. Most notably, when combined with NIR irradiation, the microneedle system achieved an outstanding antibacterial ratio of 99.4% against P. acnes and restored skin thickness to near-normal levels. Collectively, this microneedle system demonstrates a highly effective and patient-friendly approach to acne vulgaris treatment.
To report the outcomes of patients with heel pad degloving injuries, and to identify patient, injury, or treatment factors associated with successful repair. Retrospective cohort study. Single level 1 academic trauma center. All patients admitted with an acute heel pad degloving injury between 2005-2024 were included. The primary outcome was successful repair of a heel pad degloving injury. Univariate analysis was performed to examine risk factors for primary repair failure. Fifty-eight patients with acute heel pad degloving injuries were included, of whom fifty were male with average age of 35 years (range 6-69, SD 17). Forty patients were treated with an attempt at primary repair, three were treated primarily with a flap, and 15 were treated with primary amputation. Primary repair was successful in 15 patients (38%). Repair method (suture alone, augmentation with k-wires, incisional wound vac) was not associated with repair success (p>0.05 for all). Of the patients with failed primary repair, 6 underwent secondary amputation, while 19 underwent attempted salvage with a flap (13), skin graft (5), or dermal substitute (1). Of the 19 with attempted salvage, 10 (53%) had complications including persistent ulceration, infection, and/or wound breakdown. Two of this cohort underwent secondary amputation. No patients in the successful primary repair group underwent later amputation. The rate of success after attempted primary repair of heel pad degloving injuries was 38% in this series. The rate of secondary amputation was 20%. Augmenting primary repair with suture anchors or k-wires, or addition of a wound vac, was not significantly associated with improved success rates in univariate analysis, although these findings are limited by the retrospective nature of the study. Skin and soft tissue necrosis was the reason for failure of primary repair in all cases. Future studies may consider using techniques such as indocyanine green angiography to assess heel pad perfusion and identify patients at risk for failure of primary repair. Finally, although complication rates after failed primary repair were high, ultimately most limbs that underwent secondary flap reconstruction were able to be salvaged. III.
Psychodermatology is a rapidly evolving field of dermatology that bridges dermatology, clinical psychology, and psychiatry. Psychodermatological disorders comprise a significant proportion of dermatological consultations, with varying prevalence across clinical settings. Numerous classification systems exist for psychodermatological disorders. The recent international consensus has established comprehensive multidimensional frameworks. This review focuses on primary psychiatric disorders, which have a psychiatric etiology but manifest on the skin and mucosae. This group includes disorders ranging from delusional infestations and body dysmorphic disorder to body-focused repetitive behaviors and self-induced skin lesions. Each condition is discussed comprehensively, incorporating contemporary diagnostic frameworks from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the International Classification of Diseases, 11 th Revision (ICD-11), alongside evidence-based treatment modalities. A multidisciplinary, biopsychosocial approach integrating dermatological and psychiatric care is central to effective management, utilizing pharmacotherapy, cognitive behavioral therapy, and supportive psychotherapy while addressing the dermatological aspects.
The quality of dataset annotations used to train markerless motion capture models is crucial for obtaining reliable joint center estimations from videos. Because manually annotated datasets such as COCO are unsuitable for biomechanical applications, a common recommendation is to use videos synchronized with marker-based MoCap datasets. In these systems, reflective markers are placed on the skin surface, ideally on bony landmarks, and are then tracked by optical cameras to obtain highly accurate joint center annotations. While previous studies have suggested that visible reflective markers on images could bias model training, this effect has not been formally demonstrated. To address this, we used two MoCap datasets: one with 26 subjects each equipped with reflective markers mounted to rigid bodies, and the second, with 10 subjects with markers placed on bony landmarks. This allowed us to train pose estimation networks on images having visible markers. The models were then evaluated on test images with visible and inpainted markers. Our findings showed that when models were evaluated on images with markers inpainted, pixel position errors increased by +4.7% to +51.1% versus images with visible markers. This indicates that the presence of markers in training images can affect human pose estimation algorithms. To still utilize accurate annotations from MoCap, we recommend training on images with markers removed via inpainting. We also demonstrated that, in that case, the network does not rely on inpainted areas to estimate joint centers, thus making it a viable solution to the presence of markers in training images.
Staphylococcus aureus (S. aureus) is a commensal microorganism that is part of the normal human flora but has the potential to cause a wide range of infections, from superficial skin conditions to life-threatening systemic diseases such as bacteremia. The aim of this study was to evaluate the epidemiological characteristics and antimicrobial resistance patterns of S. aureus strains isolated between 2019 and 2024 at a tertiary hospital in Mogadishu, Somalia. In this retrospective study, a total of 1,381 S. aureus isolates obtained from various clinical specimens submitted from different departments to the Medical Microbiology Laboratory were analyzed. The isolates were identified using standard microbiological methods, and antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method in accordance with Clinical and Laboratory Standards Institute (CLSI) criteria. Data were statistically analyzed, and a p-value of < 0.05 was considered statistically significant. Of the 1,381 S. aureus isolates, 670 (48.51%) were identified as methicillin-resistant Staphylococcus aureus (MRSA), while 711 (51.49%) were methicillin-susceptible Staphylococcus aureus (MSSA). Of the isolates, 55.03% were obtained from male patients and 44.97% from female patients. The highest isolation rate was observed in the 18-64 year age group. Among clinical specimens, wound samples (47.57%) and blood cultures (37.14%) were the most common. Both MRSA and MSSA isolates were most frequently recovered from outpatient clinics, and a statistically significant difference was observed in distribution across clinical departments (p = 0.004). Antimicrobial susceptibility analysis revealed high resistance rates among MRSA isolates to penicillin G (98.61%), erythromycin (71.11%), and tetracycline (66%), while MSSA isolates showed high resistance to penicillin G (91.51%), tetracycline (53.57%), and levofloxacin (49.61%), while MSSA isolates showed high resistance to penicillin G (91.51%) and tetracycline (53.57%). Very low resistance rates were observed for linezolid, vancomycin, and quinupristin-dalfopristin. S. aureus remains a significant pathogen in the region, particularly due to the high prevalence of MRSA strains. The elevated resistance rates identified in this study underscore the need to tailor empirical treatment strategies based on local antibiogram data. Continuous surveillance and effective antimicrobial stewardship programs are critical for controlling the emergence and spread of antimicrobial resistance.
Information is missing on the tissue cell expression patterns of interleukin IL-33 (IL-33) and splice variants of the IL-33 receptor ST2 in normal and COPD lungs. To characterize the expression patterns of IL-33, the soluble ST2 (sST2) and membrane-bound ST2 (ST2L) splice variants in the poorly studied small airway and distal lung compartments in COPD and controls. Surgically excised lung tissue was collected from 38 COPD patients and 21 non-COPD controls. Lung compartment expression of IL-33 and ST2 and key expressing cell types were assessed histologically by combined in situ hybridization and multiplex immunohistochemistry. Expression dynamics of IL-33, ST2L and sST2 were explored by spatially resolved single-cell analysis. COPD lungs displayed increased IL-33 mRNA and IL-33 mRNA/protein ratios, suggesting increased IL-33 turnover. Total ST2/IL1RL1 mRNA levels were upregulated in COPD lungs. Mast cells constituted the major ST2-expressing immune cell population in controls and displayed a microenvironmental-specific upregulation of both ST2L and sST2 in COPD. In control alveolar regions, ST2Lhigh sST2high mast cells were present alongside IL-33-expressing general capillary (gCAp) and sST2moderate ST2Llow aerocyte (aCap) endothelial subsets. In COPD patchy alveolar regions displayed markedly elevated capillary sST2 and numbers of ST2L + and IL-33 + gCaps. By unravelling the expression patterns of IL-33 and the biologically opposing ST2L and sST2 splice variants in control and COPD lungs, the present study provides novel insights into IL-33-mediated immunity in the distal lung, information that has bearing on treatments strategies targeting this pathway in lung diseases.
Measurement of noise exposure tends to focus on sound level; however, the number of noise events might also influence health and cognition. We investigated how the distribution of noise events over time influences experiences of loudness, annoyance, and task performance. We presented recordings of a passenger aircraft flying overhead, either as a single 15-s overflight at 80 dB LeqA 15s or four 15-s overflights at 60 dB LeqA 15s . Levels were chosen on the basis that an increase of 10 dB doubles the perceived loudness, thus four stimuli at 60 dB might be expected to seem as loud as a single stimulus at 80 dB. Participants performed a mental arithmetic task during half the stimulus presentations and rated their perception of loudness and annoyance to every presentation, while pulse and skin conductance were monitored. Overall, the single 80-dB-flight stimulus was perceived as louder ( F  = 124.519, P < 0.001) and more annoying ( F  = 63.530, P < 0.001) than the four 60-dB flights. Noise did not influence task performance; however, there was an interaction ( F  = 36.256, P < 0.001) in that while doing the task, the four 60-dB flights were perceived as louder and more annoying than without the task, whereas the single 80-dB stimulus was less loud and no more annoying than without the task. Physiological markers were consistent with the intent that the task be difficult and that the single high-sound-level stimulus was more stressful for participants. Results showed that, at the levels used, the higher-level stimulus influenced ratings of loudness and annoyance, even though the lower-level stimulus occurred four times as often. Future research exploring systematically the relationship between the number and sound level of overflights and the reactions they induce is needed.
Electrical stimulation that mimics endogenous electric fields represents a promising therapeutic strategy for wound healing. In this study, a lead-free piezoelectric composite film was fabricated by incorporating (K,Na)NbO3(KNN) ceramics into a polyvinylidene fluoride (PVDF) matrix via tape casting. The introduction of KNN fillers significantly enhanced the β-phase content and piezoelectric output of PVDF. Under ultrasound irradiation, the resulting KNN/PVDF film effectively promoted fibroblast proliferation and migration in vitro, achieving a 54.84% migration rate within 24 h and upregulating key wound-repair genes, including TGF-β and VEGF. In vivo, the composite film markedly accelerated the healing of full-thickness skin defects in rats, promoted neovascularization, and achieved approximately 95% wound closure by day 9. These results demonstrate that the KNN/PVDF composite film provides an effective wireless platform for biomimetic electrical stimulation in tissue regeneration.
Chimeric antigen receptor T-cell (CAR-T) therapies have revolutionized treatment for relapsed/refractory multiple myeloma (RRMM). However, cytokine release syndrome (CRS), a common and potentially severe complication, requires inpatient monitoring, limiting access and increasing costs. Wearable devices could support outpatient CAR-T delivery, but feasibility for CRS detection versus standard care remains unproven. We conducted a prospective, single-center observational pilot study to assess the feasibility of using wearable devices for monitoring vital signs and detecting CRS. Thirty patients receiving idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel) were enrolled; 25 with sufficient monitoring data were evaluable. Sensors collected skin and axillary temperature, oxygen saturation, respiratory and heart rate, and motion. Peripheral blood cytokines were analyzed pre- and post-infusion using a multiplex proteomic platform. The primary outcome was feasibility, assessed by CRS detection sensitivity and specificity; secondary outcomes included adherence, lead time, and performance of models integrating wearable and cytokine data. CRS occurred in 20 of 25 patients. The best-performing wearable model detected 18 or 20 CRS episodes with a sensitivity of 0.72 (mean 0.75; 95% CI 0.60-0.91) and a specificity of 0.80 (mean 0.76; 95% CI 0.68-0.84), and a median lead time of 7:00 hours before nursing recognition. Median adherence during high-risk periods was 71%. Cytokine changes paralleled temperature elevations, and IFN-γ emerged as a consistent biomarker. Wearable devices are feasible for early CRS detection and may support outpatient CAR-T care. Larger outpatient studies are warranted. This study did not meet the criteria for ClinicalTrials.gov registration.
Aims and Backgrounds:
Facial and cervical aging is a multilayered process influenced by skeletal support, soft-tissue volume and position, ligamentous integrity, and skin quality. Ancestry-associated anatomic variation may affect clinical presentation, but surgical planning must remain anatomy-based rather than race-defined. This review outlines contemporary strategies for management of the heavy neck in ethnically diverse patients. 
In many ethnic patients, neck aging is driven predominantly by deep structural changes rather than early cutaneous laxity. Thicker dermis, heavier soft tissues, relative chin retrusion, and preserved dermal elasticity predispose to progressive cervicomental obtuseness. Patients presenting with obtuse cervicomental contours related to deep cervical structures benefit most from anatomy-directed intervention rather than superficial fat reduction alone. 
Management frequently includes submental deep neck contouring with selective reduction of subplatysmal fat, anterior digastric bellies, and submandibular glands, combined with platysmaplasty, with or without conservative subcutaneous fat removal. Optimal outcomes often require integration with facial rejuvenation, incorporating extended facelift techniques that emphasize comprehensive retaining-ligament release rather than traditional SMAS lift procedures. 
Surgical strategy should be guided by individual anatomy rather than ethnoracial categorization. Anatomy-based, patient-centered planning enables natural, balanced, and durable cervicofacial outcomes while preserving patient-specific aesthetic identity.
Zasocitinib is a novel highly selective tyrosine kinase 2 (TYK2) inhibitor that is in late phase development for the treatment of psoriasis and psoriatic arthritis. This article will review its efficacy, safety and tolerability. Currently, deucravacitinib is the only TYK2 inhibitor with regulatory approval from most major authorities. Zasocitinib offers potential benefits, as it has higher target selectivity and affinity of the Janus homology 2 (JH2) domain of TYK2 as compared to deucravacitinib. This selectivity leads to minimal inhibition of Janus kinase (JAK) 1, JAK2 and JAK3 (JAK1-3), and therefore may result in less off-target effects that have been associated with other molecules.