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Abstract PD-1 (programmed Death-1) immune checkpoint inhibitors have provided significant benefits to tumor patients. However, a considerable proportion of the patients develop immune-related adverse events (irAEs), of which cutaneous irAEs (cirAEs, e.g., psoriasis) occur relatively early. This review provides an overview of the current progress in psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. It not only describes the relevant influencing factors but also theoretically analyzes the immunological mechanisms that lead to the onset or exacerbation of psoriasis. Finally, the authors present guidelines for the treatment of psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. The review is intended to assist dermatologists in the early recognition and effective individualized management of such cirAE, which is helpful to continue or adjust the tumor-targeted immunotherapy on the basis of ensuring the quality of life of tumor patients.

Abstract Introduction Blaschko linear psoriasis (BLP) is characterized by the linear distribution of psoriatic skin lesions along the Blaschko lines. BLP can be divided into type I and type II, mainly on the basis of clinical manifestations. BLP can easily cause psychological burdens in patients and clinical confusion for physicians. Here, we summarize clinical cases to provide a better understanding of BLP. Methods The subjects included patients with BLP who visited our dermatology departments and those reported in the literature obtained from the PubMed and Wanfang databases. Quantitative data were presented as means ± SD (standard deviation), and qualitative data were represented by the frequency. Student’s t test was employed to compare means, whereas chi-square tests were used for analyzing qualitative data. Results A total of 74 patients with BLP (5 our patients, 69 from literature) were included, with 61 type I and 13 type II patients. We summarize BLP’s characteristics as follows: (1) More frequent in male individuals, especially in type II; (2) Earlier onset than classical psoriasis; (3) Mainly distributed unilaterally, and no preference for left or right site; (4) Asymptomatic or slight pruritus; (5) Mostly negative family history of psoriasis; (6) Possible involvement of the nails/scalp (mainly for type II); (7) Possible exogenous triggering or aggravation factors; (8) Possible concomitant classical plaque or guttate psoriasis lesions, especially in type II; (9) Conforming to histopathology features of classical psoriasis; (10) Relatively favorable response to antipsoriatic treatment, although poor for superimposed areas in type II. Conclusion This study analyzed the clinical characteristics and therapeutic aspects of BLP. Compared with published studies, we have new findings, such as gender bias. Besides traditional antipsoriatic treatment, a personalized selection of biologics may also be a promising choice. Dermatologists should recognize and understand the significance of this disease, and provide patients with appropriate psychological counseling and clinical treatments.

Letermovir is a specific inhibitor of cytomegalovirus (CMV) terminase complex. Several studies have reported that letermovir can effectively prevent CMV activation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of letermovir prophylaxis for CMV infection after allo-HSCT with a systemic review and meta-analysis. A literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. PubMed and Embase databases were searched. A total of 28 studies were included. The incidence of CMV activation at 14 weeks after HSCT was 0.10 (95% confidence interval [CI], 0.06–0.18), which was 0.10 (95% CI, 0.04–0.21) and 0% in adult and children (2 studies were included and both of them were 0%). In addition, the incidence of CMV activation at 14 weeks after allo-HSCT was 0.11 (95% CI, 0.06–0.21) and 0.07 (only 1 study included), respectively, in retrospective and prospective studies. The incidence of CMV activation at 100 and 200 days after HSCT was 0.23 (95% CI, 0.16–0.33) and 0.49 (95% CI, 0.32–0.67), respectively. The incidence of CMV disease at 14 weeks and at 6 months after HSCT was 0.01 (95% CI, 0.01–0.02) and 0.03 (95% CI, 0.01–0.09), respectively. Thus, our systemic review and meta-analysis suggested that letermovir prophylaxis was safe and effective for CMV activation after allo-HSCT.

Objectives: To investigate the characteristics of the skin microbiome in severe afatinib-induced skin toxicity. Methods: Body site-matched skin surface samples were collected from the lesions on seven flexural sites of one lung cancer (Patient 1) with serious systemic drug-related intertriginous and flexural exanthema (SDRIFE)-like toxicity induced by EGFR-TKI and three healthy age/sex matched controls for whole metagenomics sequencing analysis. Lung cancer Patient 1 and Patient 2 were prescribed minocycline and followed up. Results: In SDRIFE-like toxicities induced by afatinib, lesion microbiota richness (ACE and Chao1 index: p

Epstein-Barr virus (EBV) reactivation is one of the most important infections after hematopoietic stem cell transplantation (HSCT) using haplo-identical related donors (HID). We aimed to establish a comprehensive model with machine learning, which could predict EBV reactivation after HID HSCT with anti-thymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis. We enrolled 470 consecutive acute leukemia patients, 60% of them (n = 282) randomly selected as a training cohort, the remaining 40% (n = 188) as a validation cohort. The equation was as follows: Probability (EBV reactivation) = 11 + exp(−Y), where Y = 0.0250 × (age) – 0.3614 × (gender) + 0.0668 × (underlying disease) – 0.6297 × (disease status before HSCT) – 0.0726 × (disease risk index) – 0.0118 × (hematopoietic cell transplantation-specific comorbidity index [HCT-CI] score) + 1.2037 × (human leukocyte antigen disparity) + 0.5347 × (EBV serostatus) + 0.1605 × (conditioning regimen) – 0.2270 × (donor/recipient gender matched) + 0.2304 × (donor/recipient relation) – 0.0170 × (mononuclear cell counts in graft) + 0.0395 × (CD34+ cell count in graft) – 2.4510. The threshold of probability was 0.4623, which separated patients into low- and high-risk groups. The 1-year cumulative incidence of EBV reactivation in the low- and high-risk groups was 11.0% versus 24.5% (P < .001), 10.7% versus 19.3% (P = .046), and 11.4% versus 31.6% (P = .001), respectively, in total, training and validation cohorts. The model could also predict relapse and survival after HID HSCT. We established a comprehensive model that could predict EBV reactivation in HID HSCT recipients using ATG for GVHD prophylaxis.

IntroductionThe modulation of immunometabolic pathways is emerging as a promising therapeutic target for immune-mediated diseases. However, the immunometabolic features of psoriatic disease and the potential targets for immunometabolic intervention in the different T-cell subsets involved in its pathogenesis remain unclear.MethodsIn this study, we analyzed circulating blood single-cell data from healthy controls (HC), psoriasis (PSO), and psoriatic arthritis (PSA) patients, and revealed their metabolic features of T-cell subsets: CD4+ central memory T cells (TCMs), CD8+ effective memory T cells (TEMs), regulatory T cells (Tregs), mucosal-associated invariant T cells (MAITs ), and γδ T cells. Pearson test was performed to determine the linkages between differential metabolic and inflammatory pathways. Based on these results, we also analyzed the potential impacts of biological antibodies on differential metabolic pathways by comparing the immunometabolism differences between PSA patients without and with biological treatment.ResultsOur results suggest that upregulation of ascorbate and aldarate metabolism, as well as fatty acid degradation, may enhance the immune suppression of Tregs. Enhanced metabolism of alpha-linolenic acid, linoleic acid, and arachidonic acid may inhibit the pro-inflammatory functions of CD4+ TCMs and CD8+ TEMs in PSO and PSA, and protect the immune suppression of Tregs in PSA. We propose that supporting ascorbic acid and fatty acid metabolic pathways may be an adjunctive reprogramming strategy with adalimumab and etanercept therapy.DiscussionThese findings not only provide insights into immunometabolism characteristics of psoriatic disease, but also offer preliminary options for the auxiliary treatment of psoriasis.

Abstract Background Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a comprehensive model which could predict severe aGVHD after HID HSCT. Methods Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://clinicaltrials.gov (NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected as training cohort and the remains 30% (n = 135) were used as validation cohort. Results The equation was as follows: Probability (grade III–IV aGVHD) = $$\frac{1}{{1 + \exp \left( { - \,{\text{Y}}} \right)}}$$ 1 1 + exp - Y , where Y = –0.0288 × (age) + 0.7965 × (gender) + 0.8371 × (CD3 + /CD14 + cells ratio in graft) + 0.5829 × (donor/recipient relation) − 0.0089 × (CD8 + cell counts in graft) − 2.9046. The threshold of probability was 0.057392 which helped separate patients into high- and low-risk groups. The 100-day cumulative incidence of grade III–IV aGVHD in the low- and high-risk groups was 4.1% (95% CI 1.9–6.3%) versus 12.8% (95% CI 7.4–18.2%) (P = 0.001), 3.2% (95% CI 1.2–5.1%) versus 10.6% (95% CI 4.7–16.5%) (P = 0.006), and 6.1% (95% CI 1.3–10.9%) versus 19.4% (95% CI 6.3–32.5%) (P = 0.017), respectively, in total, training, and validation cohort. The rates of grade III–IV skin and gut aGVHD in high-risk group were both significantly higher than those of low-risk group. This model could also predict grade II–IV and grade I–IV aGVHD. Conclusions We established a model which could predict the development of severe aGVHD in HID HSCT recipients.

Actinic keratosis (AK) is a common precancerous skin lesion with significant harm, and it is often confused with non-actinic keratoses (NAK). At present, the diagnosis of AK mainly depends on clinical experience and histopathology. Due to the high difficulty of diagnosis and easy confusion with other diseases, this article aims to develop a convolutional neural network that can efficiently, accurately, and automatically diagnose AK. This article improves the MobileNet model and uses the AK and NAK images in the HAM10000 dataset for training and testing after data preprocessing, and we performed external independent testing using a separate dataset to validate our preprocessing approach and to demonstrate the performance and generalization capability of our model. It further compares common deep learning models in the field of skin diseases (including the original MobileNet, ResNet, GoogleNet, EfficientNet, and Xception). The results show that the improved MobileNet has achieved 0.9265 in accuracy and 0.97 in Area Under the ROC Curve (AUC), which is the best among the comparison models. At the same time, it has the shortest training time, and the total time of five-fold cross-validation on local devices only takes 821.7 s. Local experiments show that the method proposed in this article has high accuracy and stability in diagnosing AK. Our method will help doctors diagnose AK more efficiently and accurately, allowing patients to receive timely diagnosis and treatment.

ObjectiveWe aimed to establish a model that can predict refractory/recurrent cytomegalovirus (CMV) infection after haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT).MethodsConsecutive acute leukemia patients receiving HID HSCT were enrolled (n = 289). We randomly selected 60% of the entire population (n = 170) as the training cohort, and the remaining 40% comprised the validation cohort (n = 119). Patients were treated according to the protocol registered at https://clinicaltrials.gov (NCT03756675).ResultsThe model was as follows: Y = 0.0322 × (age) – 0.0696 × (gender) + 0.5492 × (underlying disease) + 0.0963 × (the cumulative dose of prednisone during pre-engraftment phase) – 0.0771 × (CD34+ cell counts in graft) – 1.2926. The threshold of probability was 0.5243, which helped to separate patients into high- and low-risk groups. In the low- and high-risk groups, the 100-day cumulative incidence of refractory/recurrent CMV was 42.0% [95% confidence interval (CI), 34.7%–49.4%] vs. 63.7% (95% CI, 54.8%–72.6%) (P < 0.001) for total patients and was 50.5% (95% confidence interval (CI), 40.9%–60.1%) vs. 71.0% (95% CI, 59.5%–82.4%) (P = 0.024) for those with acute graft-versus-host disease. It could also predict posttransplant mortality and survival.ConclusionWe established a comprehensive model that could predict the refractory/recurrent CMV infection after HID HSCT.Clinical Trial Registrationhttps://clinicaltrials.gov, identifier NCT03756675.

Benzo (α) pyrene in soybean oil was determined by molecular imprinting column purification combined with high performance liquid chromatography (MIC-HPLC).The whole process was analyzed to evaluate the uncertainty of the analytical results.Meanwhile, the uncertainty components were quantified and synthesized by a metrological model of uncertainty.Furthermore, the extended uncertainty of the measurement results was calculated.The results showed that the main factors which affected the uncertainty were the calibration curve, recovery, sample weighting and working solution preparation.When the content of benzo (α) pyrene in soybean oil was 8.735 μg/kg, at 95% confidence interval, the expanded uncertainty was 0.794 μg/kg (k=2).The uncertainty of benzo (α) pyrene in edible oil determined by MIC-HPLC can be reduced by strictly control the processes of the curve fitting, recovery, sample weighting and working solution preparation.

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺1-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907). Federated across two ARD cohorts, we find that patients exposed to ⍺1-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR = 0.70, p = 0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of ⍺1-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.