Updated cutaneous T-cell lymphoma TNMB staging criteria fail to identify Sézary syndrome patients with low blood burden.

Comparison of the 2007 EORTC/ISCL and the 2022 EORTC/ISCL/USCLC blood staging guidelines for cutaneous T-cell lymphoma at a single institution reveals the newer guidelines fail to detect a subset of Sézary syndrome patients with low blood burden.

Rapid measurement of epidermal thickness in OCT images of skin.

Epidermal thickness (ET) changes are associated with several skin diseases. To measure ET, segmentation of optical coherence tomography (OCT) images is essential; manual segmentation is very time-consuming and requires training and some understanding of how to interpret OCT images. Fast results are important in order to analyze ET over different regions of skin in rapid succession to complete a clinical examination and enable the physician to discuss results with the patient in real time. The well-known CNN-graph search (CNN-GS) methodology delivers highly accurate results, but at a high computational cost. Our objective was to build a computational core, based on CNN-GS, able to accurately segment OCT skin images in real time. We accomplished this by fine-tuning the hyperparameters, testing a range of speed-up algorithms including pruning and quantization, designing a novel pixel-skipping process, and implementing the final product with efficient use of core and threads on a multicore central processing unit (CPU). We name this product CNN-GS-skin. The method identifies two defined boundaries on OCT skin images in order to measure ET. We applied CNN-GS-skin to OCT skin images, taken from various body sites of 63 healthy individuals. Compared with CNN-GS, our described method reduced computation time by 130 [Formula: see text] with minimal reduction in ET determination accuracy (from 96.38 to 94.67%).

Chemical exposures and demographic associations in cutaneous T-cell lymphoma: a large single institution physician validated cohort study.

Cutaneous T-cell lymphomas (CTCL) are a rare group of T-cell neoplasms which infiltrate the skin and can result in substantial morbidity and mortality. Risk factors for CTCL are still poorly understood though recent studies suggest chemical exposures may play a role in its development. To further characterize patient-centered risk factors for CTCL, especially compared with matched controls, we performed one of the largest prospective cohort survey studies to date to examine patient-reported exposures and health-related quality of life (HRQoL) in association with concurrent clinical disease characteristics. Patient demographics, lifestyle factors, and chemical exposures were collected via clinical data and surveys. Descriptive statistics, ANOVA, Chi-square tests and t tests were utilized to compare patient-reported exposures and HRQoL in patients with CTCL versus matched healthy controls (HC). Statistically significant differences were identified between patients and HC in terms of race (non-white race 22.4% in CTCL patients vs. 18.8% in HC, P = 0.01), and education level (high school or less 41.6% in CTCL patients vs. 14.3% in HC, P = 0.001), but not with Fitzpatrick skin type (P = 0.11) or smoking status (P = 0.28). Notably, 36.0% of the CTCL patients reported exposures to chemicals, a near threefold increased percentage when compared to HC (12.9%). Among various chemical exposures, 27.0% of the CTCL patients specifically reported industrial chemical exposure, a more than two-fold increased percentage when compared to HC (12.9%). Itch and pain were significantly associated with skin disease severity (as evaluated by CTCL-specific mSWAT score) in advanced stage disease (stages IIB-IVB) (r = 0.48 and 0.57, P < 0.05). Itch and body mass index (BMI) were weakly associated with skin disease severity in early-stage disease (stages IA-IIA) (r = 0.27 and 0.20, P < 0.05).

Lifestyle, demographic and Skindex measures associated with cutaneous T-cell lymphoma: a single institution cohort study.

Cutaneous T-cell lymphoma (CTCL) risk factors and associated quality of life are poorly understood. Previous studies of CTCL risk factors explored patient comorbidities and lifestyle exposures, but not in conjunction with disease stage, subtype, severity, or health-related quality of life (HRQoL). We investigated lifestyle exposures and demographic factors associated with advanced-stage disease, increased disease severity, and poorer HRQoL outcomes in this single-center cohort study. A cohort survey study was conducted at Northwestern's Multidisciplinary Cutaneous Lymphoma specialty clinic between April 2019 and June 2021. REDCap surveys were administered to 140 patients with CTCL, investigating patients' demographics, lifestyle and chemical exposures. QoL was evaluated using the Skindex survey; pain and itch with ten-point Likert scales. Modified Severity Weighted Assessment Tool (mSWAT), disease stage, and disease subtype were confirmed upon enrollment in the study by a single board-certified dermatologist specializing in CTCL. Factors were compared by t test or Fischer's exact test. Median age was 63 years (range 14-92) with male-to-female ratio of 1.2:1. The most common diagnosis was CD4 + MF (n = 94, 67.1%). Common lifestyle exposures included smoking (past or current) (52.3%) and chemical exposure history (all sources [53.7%]; industrial only [33.0%]). History of chemical exposures were associated with advanced stage disease (p = 0.003) and worse QoL outcomes (p = 0.001). There were significant racial differences, respectively, in early (I-IIA) vs late (IIB-IV) stage disease (p = 0.003). Obesity, hygiene, smoking, recent sun exposure, education and atopy were not significantly associated with disease stage or severity. We provide an analysis of lifestyle and demographic factors in the context of CTCL disease severity, stage, and HRQoL. We identified race as a potential risk factor for advanced stage disease and both skin phototype and chemical exposures as a risk factor for increased disease severity as measured by mSWAT. QoL outcomes were multifactorial and significantly associated with history of chemical exposure, severe pain/itch, race, disease stage and subtype. An improved understanding of these associations may lead to better individualized care. As chemical exposure and race were found to be significant factors associated with advanced-stage disease, taking exposure histories and addressing racial disparities may improve care for CTCL patients.

Retrospective analysis of sepsis in cutaneous T-cell lymphoma reveals significantly greater risk in Black patients.

BACKGROUND: Sepsis is a leading cause of morbidity, mortality, and resource utilization among patients with cutaneous T-cell lymphoma (CTCL). OBJECTIVE: To characterize the demographic, clinical, and microbial attributes distinguishing patients with CTCL sepsis from other patients with non-Hodgkin lymphoma (NHL) sepsis and patients with CTCL in general. METHODS: Two-part retrospective cohort study at an academic medical center from 2001-2019 involving patients with CTCL (n = 97) and non-CTCL NHL (n = 88) admitted with sepsis, and a same-institution CTCL patient database (n = 1094). Overall survival was estimated by Kaplan-Meier analyses. RESULTS: Patients with CTCL sepsis were more likely to be older, Black, experience more sepsis episodes, die or be readmitted within 30 days of an inpatient sepsis episode, and develop Gram-positive bacteremia than patients with non-CTCL NHL sepsis. Staphylococcus aureus and Escherichia coli were the most frequently speciated organisms in CTCL (26%) and non-CTCL NHL (14%), respectively. No between-group differences were identified regarding sex, presence of central line, chemotherapy use, or disease stage. Compared with general patients with CTCL, patients with sepsis were Black and exhibited advanced-stage disease, higher body surface area involvement, and higher lactate dehydrogenase levels. LIMITATIONS: Single institution, retrospective nature may limit generalizability. CONCLUSION: Awareness of CTCL-specific risk factors is crucial for guiding sepsis prevention and improving patient outcomes.

Nasal Dysbiosis in Cutaneous T-Cell Lymphoma Is Characterized by Shifts in Relative Abundances of Non-Staphylococcus Bacteria.

The nasal microbiome of patients with cutaneous T-cell lymphoma (CTCL) remains unexplored despite growing evidence connecting nasal bacteria to skin health and disease. Nasal swabs from 45 patients with CTCL (40 with mycosis fungoides, 5 with Sézary syndrome) and 20 healthy controls from the same geographical region (Chicago Metropolitan Area, Chicago, IL) were analyzed using sequencing of 16S ribosomal RNA and tuf2 gene amplicons. Nasal α-diversity did not differ between mycosis fungoides/Sézary syndrome and healthy controls (Shannon index, genus level, P = 0.201), but distinct microbial communities were identified at the class (R2 = 0.104, P = 0.023) and order (R2 = 0.0904, P = 0.038) levels. Increased relative abundance of the genera Catenococcus, Vibrio, Roseomonas, Acinetobacter, and unclassified Clostridiales was associated with increased skin disease burden (P < 0.005, q < 0.05). Performed to accurately resolve nasal Staphylococcus at the species level, tuf2 gene amplicon sequencing revealed no significant differences between mycosis fungoides/Sézary syndrome and healthy controls. Although S. aureus has been shown to worsen CTCL through its toxins, no increase in the relative abundance of this taxon was observed in nasal samples. Despite the lack of differences in Staphylococcus, the CTCL nasal microbiome was characterized by shifts in numerous other bacterial taxa. These data add to our understanding of the greater CTCL microbiome and provide context for comprehending nasal-skin and host‒tumor‒microbial relationships.

Treatment with the antipsychotic risperidone is associated with increased M1-like JAK-STAT1 signature gene expression in PBMCs from participants with psychosis and THP-1 monocytes and macrophages.

Clinical studies demonstrate alterations to immune measures in psychosis that can vary with illness stage and severity. For example, recent data show that changes to the JAK-STAT1 transcriptional signature, characteristic of an "M1" proinflammatory monocyte and macrophages phenotype, are related to illness duration. While antipsychotics have demonstrated immunomodulatory properties, their effects on this important immune signaling pathway are unknown. The primary aims of this study were to determine the effects of risperidone, a commonly prescribed antipsychotic drug, on the JAK-STAT1 transcriptional signature. Selected measures of JAK-STAT1 signature gene expression in peripheral blood mononuclear cells (PBMCs) from a clinical sample with psychosis were compared to examine differences induced by risperidone treatment. Additionally, the direct effects of risperidone on the JAK-STAT1 signature were investigated using a THP-1 human monocyte and macrophage cell model. Comparisons within the clinical sample demonstrated that the JAK-STAT1 signature was elevated in PBMCs from participants treated with risperidone who had a longer illness duration compared to untreated participants and those who were risperidone treated but had a shorter illness duration. Results of the in-vitro experiments showed a consistent potentiating effect of risperidone on expression of JAK-STAT1 signature genes in activated monocytes and monocyte-derived macrophages. Collectively these data indicate that risperidone may skew myeloid cells to a more proinflammatory phenotype, potentially contributing to increases in expression of JAK-STAT1 signature genes in participants with a longer illness duration.

The JAK-STAT1 transcriptional signature in peripheral immune cells reveals alterations related to illness duration and acuity in psychosis.

Multiple lines of inquiry demonstrate alterations to immune function in psychosis. Clinically, this is reflected by elevated proinflammatory cytokines in serum, indicating activation of circulating immune cells. Data from isolated cells in clinical populations support the presence of altered activity of pertinent intracellular signaling pathways. Here, we focus on the well-characterized IFN-γ mediated JAK-STAT1 signaling pathway, which is involved in multiple aspects of immunity, including activation of circulating immune cells to a proinflammatory phenotype. By measuring a transcriptional signature characteristic of activation of this pathway, we demonstrate that JAK-STAT1 signature gene expression is suppressed in participants with psychosis who are early in illness and in participants who are hospitalized with an acute exacerbation of psychosis. Furthermore, we find that this expression signature normalizes in participants who have a longer illness duration and chronic, but not acute, psychopathology. This relationship of JAK-STAT1 signature gene expression with clinical characteristics highlights the temporal and contextual complexity of alterations to immune activity in psychosis and provides important insight into the functional state of circulating immune cells. These findings are of particular interest given recent research illustrating the importance of peripherally derived immune cells and the effectors they secrete in mediating neurophysiological processes of relevance for psychiatric illness.

Dual-functionalized poly(amidoamine) dendrimers with poly(ethylene glycol) conjugation and thiolation improved blood compatibility.

OBJECTIVES: This study aims to examine the blood compatibility of dual-functionalized poly(amidoamine) (PAMAM) dendrimers. METHODS: The cationic PAMAM dendrimer of generation 4.0 (PM4.0) were functionalized by poly(ethylene glycol) (PEG) conjugation or by thiolation or the combination of both methods. Various in-vitro assays including immune cell cytotoxicity, haemoglobin release, serum albumin binding, complement activation and coagulation times were used to characterize the compatibility with blood components. KEY FINDINGS: Although thiolation of polymers has been reported as a strategy to reduce platelet activation or aggregation, thiolation of PM4.0 alone did not offer any protective effect against the dendrimer toxicity on blood components or functions. PEGylation was able to reduce the toxic effect and interactions of the unmodified and thiolated PM4.0 on various blood components and functions; yet, PEGylated PM4.0 displayed prolonged prothrombin times and activated partial thromboplastin times. Among various PM4.0 derivatives, dual-functionalized PM4.0 with PEG and thiol groups displayed the least toxicity to various blood components and functions. CONCLUSIONS: Our findings suggested that comprehensive studies of dendrimer biocompatibility should be performed so as to establish the safe dose window for systemic administration.