Clinical features and treatment outcomes of liver involvement in paediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, and liver involvement in LCH is rare. This retrospective study reported the clinical features and prognosis of patients with hepatic LCH. Liver involvement was defined by histopathological findings, liver dysfunction or abnormalities, or ultrasound imaging. A total of 130 patients (14.5%) with hepatic LCH out of 899 in the LCH population were enrolled. Patients with liver involvement had greater frequencies of skin, lung, hearing system, and haematologic system involvement, and hemophagocytic lymphohistiocytosis (P<0.001, 0.001, 0.002, 0.009, and <0.001, respectively). Overall survival and progression-free survival were lower in LCH patients with liver involvement than in those without liver involvement (P<0.001 and <0.001). In patients with liver involvement, the overall survival (OS) and progression-free survival (PFS) rates were lower in patients with cholangitis than in those without cholangitis (P<0.020 and 0.030). For the treatment response, the response rate of hepatic LCH patients to initial first-line therapy (n=89) was 22.5%. However, there was no significant difference in the response rate or recurrence rate between patients who shifted from first-line treatment to second-line treatment (n=29) or to targeted therapy (n=13) (P=0.453 and 1.000). The response rate of hepatic LCH patients who received initial second-line therapy (n=13) was 38.5%. Two of these patients subsequently experienced bone recurrence. The response rate of hepatic LCH patients who received initial targeted therapy (n=16) was 75.0%. Three patients subsequently experienced recurrence, including 2 in the bone and 1 in the liver and skin. A total of 39.3% of patients who received second-line treatment had severe myelosuppression (grade III-IV), and 50.8% had varying degrees of gastrointestinal events, whereas there was no severe toxicity in patients who received first-line treatment and targeted therapy. Four patients underwent liver transplantation because of liver cirrhosis. The patients' liver disease improved within a follow-up period of 18-79 months. This study demonstrated that LCH with liver involvement, especially cholangitis, indicates a poor prognosis. Targeted therapy provides a good treatment response and less toxicity. However, it may relapse after withdrawal. Liver transplantation is still a reliable salvage option for patients with end-stage liver disease.

Temporal landscape and translational regulation of A-to-I RNA editing in mouse retina development.

BACKGROUND: The significance of A-to-I RNA editing in nervous system development is widely recognized; however, its influence on retina development remains to be thoroughly understood. RESULTS: In this study, we performed RNA sequencing and ribosome profiling experiments on developing mouse retinas to characterize the temporal landscape of A-to-I editing. Our findings revealed temporal changes in A-to-I editing, with distinct editing patterns observed across different developmental stages. Further analysis showed the interplay between A-to-I editing and alternative splicing, with A-to-I editing influencing splicing efficiency and the quantity of splicing events. A-to-I editing held the potential to enhance translation diversity, but this came at the expense of reduced translational efficiency. When coupled with splicing, it could produce a coordinated effect on gene translation. CONCLUSIONS: Overall, this study presents a temporally resolved atlas of A-to-I editing, connecting its changes with the impact on alternative splicing and gene translation in retina development.

LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.

Pancreatic cancer is a malignancy with high mortality. In addition to the few symptoms until the disease reaches an advanced stage, the high fatality rate is attributed to its rapid development, drug resistance and lack of appropriate treatment. In the selection and research of therapeutic drugs, gemcitabine is the first-line drug for pancreatic cancer. Solving the problem of gemcitabine resistance in pancreatic cancer will contribute to the progress of pancreatic cancer treatment. Long non coding RNAs (lncRNAs), which are RNA transcripts longer than 200 nucleotides, play vital roles in cellular physiological metabolic activities. Currently, our group and others have found that some lncRNAs are aberrantly expressed in pancreatic cancer cells, which can regulate the process of cancer through autophagy and Wnt/ß-catenin pathways simultaneously and affect the sensitivity of cancer cells to therapeutic drugs. This review presents an overview of the recent evidence concerning the node of lncRNA for the cross-talk between autophagy and Wnt/ß-catenin signaling in pancreatic cancer, together with the practicability of lncRNAs and the core regulatory factors as targets in therapeutic resistance.

Harmonizing tumor mutational burden analysis: Insights from a multicenter study using in silico reference data sets in clinical whole-exome sequencing (WES).

OBJECTIVES: Tumor mutational burden (TMB) is a significant biomarker for predicting immune checkpoint inhibitor response, but the clinical performance of whole-exome sequencing (WES)-based TMB estimation has received less attention compared to panel-based methods. This study aimed to assess the reliability and comparability of WES-based TMB analysis among laboratories under routine testing conditions. METHODS: A multicenter study was conducted involving 24 laboratories in China using in silico reference data sets. The accuracy and comparability of TMB estimation were evaluated using matched tumor-normal data sets. Factors such as accuracy of variant calls, limit of detection (LOD) of WES test, size of regions of interest (ROIs) used for TMB calculation, and TMB cutoff points were analyzed. RESULTS: The laboratories consistently underestimated the expected TMB scores in matched tumor-normal samples, with only 50% falling within the ±30% TMB interval. Samples with low TMB score (<2.5) received the consensus interpretation. Accuracy of variant calls, LOD of the WES test, ROI, and TMB cutoff points were important factors causing interlaboratory deviations. CONCLUSIONS: This study highlights real-world challenges in WES-based TMB analysis that need to be improved and optimized. This research will aid in the selection of more reasonable analytical procedures to minimize potential methodologic biases in estimating TMB in clinical exome sequencing tests. Harmonizing TMB estimation in clinical testing conditions is crucial for accurately evaluating patients' response to immunotherapy.

A radiograph-based deep learning model improves radiologists' performance for classification of histological types of primary bone tumors: A multicenter study.

PURPOSE: To develop a deep learning (DL) model for classifying histological types of primary bone tumors (PBTs) using radiographs and evaluate its clinical utility in assisting radiologists. METHODS: This retrospective study included 878 patients with pathologically confirmed PBTs from two centers (638, 77, 80, and 83 for the training, validation, internal test, and external test sets, respectively). We classified PBTs into five categories by histological types: chondrogenic tumors, osteogenic tumors, osteoclastic giant cell-rich tumors, other mesenchymal tumors of bone, or other histological types of PBTs. A DL model combining radiographs and clinical features based on the EfficientNet-B3 was developed for five-category classification. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate model performance. The clinical utility of the model was evaluated in an observer study with four radiologists. RESULTS: The combined model achieved a macro average AUC of 0.904/0.873, with an accuracy of 67.5 %/68.7 %, a macro average sensitivity of 66.9 %/57.2 %, and a macro average specificity of 92.1 %/91.6 % on the internal/external test set, respectively. Model-assisted analysis improved accuracy, interpretation time, and confidence for junior (50.6 % vs. 72.3 %, 53.07[s] vs. 18.55[s] and 3.10 vs. 3.73 on a 5-point Likert scale [P < 0.05 for each], respectively) and senior radiologists (68.7 % vs. 75.3 %, 32.50[s] vs. 21.42[s] and 4.19 vs. 4.37 [P < 0.05 for each], respectively). CONCLUSION: The combined DL model effectively classified histological types of PBTs and assisted radiologists in achieving better classification results than their independent visual assessment.

Association between incorrect postures and curve magnitude of adolescent idiopathic scoliosis in china.

BACKGROUND: Despite advancements in school scoliosis screening (SSS), there are still no effective indicators to estimate the severity of spinal curvature. We aim to investigate the association between incorrect postures and curve magnitude of adolescent idiopathic scoliosis (AIS) among Chinese adolescents. METHODS: In this SSS program, we examined the incorrect posture, Adam's forward bending test (FBT) results, and angle of trunk rotation (ATR) in adolescents. Those with suspected scoliosis were referred for a standing anteroposterior whole-spine radiography as outpatients. The radiographic data of 426 students with lateral Cobb angles were collected from 2016 to 2022 and the associations were studied using logistic regression (LR) models and receiver operating characteristic (ROC) curves. RESULTS: Univariate LR revealed that female gender [odds ratio (OR) = 2.92, 95% confidence interval (CI) 1.67-5.09, P < 0.001], age 16-19y (OR = 2.83, 95%CI 1.10-7.28, P = 0.031), right shoulder height (OR = 2.15, 95%CI 1.23-3.75, P = 0.007), right scapula tilt (OR = 2.03, 95%CI 1.18-3.50, P = 0.010), right rib hump (OR = 1.88, 95%CI 1.23-2.85, P = 0.003), right thoracic rotation ≥ 5° (OR = 2.14, 95%CI 1.43-3.20, P < 0.001), and left thoracolumbar kyphosis (OR = 3.79, 95%CI 1.06-13.56, P = 0.041) were all significantly associated with the severity of the curve magnitude. Multivariate LR showed that female gender [adjusted OR (AOR) = 3.23, 95%CI 1.81-5.73, P < 0.001], those aged 16-19y (AOR = 5.08, 95%CI 1.86-13.91, P = 0.002), and with a right rib hump (AOR = 1.72, 95%CI 1.11-2.64, P = 0.015) presented with a higher risk of severe curve magnitude than men, those aged 7-12y, and without a rib hump, respectively. ROC curves further proved that sex, age, shoulder-height difference, scapula tilt, flat back, rib hump, angle of thoracic rotation were the risk predictors for curve magnitude. CONCLUSION: Incorrect posture and ATR, especially the right rib hump, were significantly associated with the curve magnitude of AIS. Early screening for incorrect postures and ATR could be an effective and economical strategy to predict the severity of AIS through SSS in Chinese adolescents.

Treg-derived TGF-ß1 dampens cGAS-STING signaling to downregulate the expression of class I MHC complex in multiple myeloma.

Multiple myeloma (MM) progression involves diminished tumor antigen presentation and an immunosuppressive microenvironment, characterized by diminished expression of major histocompatibility complexes (MHC) class I molecule and elevated programmed death ligand 1 (PDL1) in MM cells, along with an enriched population of regulatory T cells (Tregs). To investigate Treg's influence on MM cells, we established a co-culture system using Tregs from MM patients and the MM cell lines (MM.1S and SK-MM-1) in vitro and assessed the effects of intervening in the relevant pathways connecting Tregs and MM cells in vivo. In vitro, Tregs induced transforming growth factor beta-1 (TGF-ß1) production, downregulated MHC I members, and increased PDL1 expression in MM cells. Treg-derived TGF-ß1 suppressed the cGAS-STING pathway, contributing to the loss of MHC I molecule expression and PDL1 upregulation. Correspondingly, neutralizing TGF-ß1 or activating the cGAS-STING pathway restored MHC I and PDL1 expression, effectively countering the pro-tumorigenic effect of Tregs on MM cells in vivo. These data elucidated how Tregs influence tumor antigen presentation and immunosuppressive signal in MM cells, potentially providing therapeutic strategies, such as neutralizing TGF-ß1 or activating the cGAS-STING pathway, to address the immune escape and immunosuppressive dynamics in MM.

Dual­regulated oncolytic adenovirus carrying ERCC1­siRNA gene possesses potent antitumor effect on ovarian cancer cells.

Ovarian cancer is a multifactorial and deadly disease. Despite significant advancements in ovarian cancer therapy, its incidence is on the rise and the molecular mechanisms underlying ovarian cancer invasiveness, metastasis and drug resistance remain largely elusive, resulting in poor prognosis. Oncolytic viruses armed with therapeutic transgenes of interest offer an attractive alternative to chemical drugs, which often face innate and acquired drug resistance. The present study constructed a novel oncolytic adenovirus carrying ERCC1 short interfering (si)RNA, regulated by hTERT and HIF promoters, termed Ad­siERCC1. The findings demonstrated that this oncolytic adenovirus effectively inhibits the proliferation, migration and invasion of ovarian cancer cells. Furthermore, the downregulation of ERCC1 expression by siRNA ameliorates drug resistance to cisplatin (DDP) chemotherapy. It was found that Ad­siERCC1 blocks the cell cycle in the G1 phase and enhances apoptosis through the PI3K/AKT­caspase­3 signaling pathways in SKOV3 cells. The results of the present study highlighted the critical effect of oncolytic virus Ad­siERCC1 in inhibiting the survival of ovarian cancer cells and increasing chemotherapy sensitivity to DDP. These findings underscore the potent antitumor effect of Ad­siERCC1 on ovarian cancers in vivo.

Prevalence of thyroid nodules in residents of Ukraine exposed as children or adolescents to iodine-131 from the Chornobyl accident.

BACKGROUND: Although childhood exposure to radioactive iodine-131 (I-131) is an established risk factor for thyroid cancer, evidence for an association with thyroid nodules is less clear. The objective of this study is to evaluate the association between childhood I-131 exposure and prevalence of ultrasound-detected thyroid nodules overall and by nodule histology/cytology (neoplastic/suspicious/non-neoplastic), size (<10 mm/≥10 mm), and number (single/multiple). METHODS: This is a cross-sectional study of radiation dose (mean=0.53 gray, range:0.0003-31 gray) and screen-detected thyroid nodules conducted in 1998-2000 (median population age 21.5 years) in a cohort of 13,243 residents of Ukraine who were under 18 years at the time of the Chornobyl accident on April 26, 1986. Excess odds ratios per gray (EOR/Gy) and 95% confidence intervals (95% CI) were estimated using logistic regression. RESULTS: Among 13,078 eligible individuals, we identified 358 (2.7%) with at least one thyroid nodule. Significantly increased dose-response associations were found for all nodules and nodule groups with doses <5 Gy except subjects with non-neoplastic nodules. Among subjects with doses <5 Gy, the EOR/Gy for neoplastic nodules (5.35;95% CI:2.19,15.5) was significantly higher than for non-neoplastic nodules (0.24;95% CI:-0.07,0.74), but the EOR/Gy did not vary by nodule size or number. CONCLUSIONS: Childhood exposure to I-131 is associated with an increased risk of thyroid nodules detected 12-14 years following exposure and the risk for neoplastic nodules is higher than for non-neoplastic nodules. Analyses of incident thyroid nodules may help clarify dose-response patterns by nodule characteristics and provide insights into thyroid nodule etiology.

Disruption of the Hippo pathway promotes the proliferation of childhood acute lymphoblastic leukemia cells, inhibits apoptosis and chemosensitivity.

BACKGROUND: Despite advancements in chemotherapy and stem cell transplantation, the recurrence and chemoresistance of childhood acute lymphoblastic leukemia (cALL) remain a significant challenge, thus indicating the need for novel therapeutic targets. RESEARCH DESIGN AND METHODS: The protein levels of YAP1, p-YAP1, TAZ, and Cyr61 of cALL patients and healthy volunteers were measured by western blot analysis. Then the leukemic cell line SUP-B15 was transfected with sh-YAP1 and pcDNA3.1-YAP1 to knockdown or overexpress YAP1. The viability, chemosensitivity, apoptosis, migration, and invasion of SUP-B15 cells were determined by MTT, flow cytometry, and Transwell assay. RESULTS: The cALL patients had higher YAP1, TAZ, and Cyr61 protein expression and lower p-YAP1 protein expression in bone marrow tissues compared with healthy volunteers (p < 0.01). In SUP-B15 cells, YAP1 knockdown upregulated p-YAP1 protein expression (p < 0.01) and downregulated TAZ and Cyr61 protein expression (p < 0.01). In addition, knocking down YAP1 significantly inhibited cell viability, migration, and invasion, and induced apoptosis (p < 0.01). YAP1 knockdown also reduced the IC50 value following treatment with vincristine, daunorubicin, cyclophosphamide, and dexamethasone (p < 0.05). CONCLUSIONS: Disruption of the Hippo pathway attenuates the development of cALL by promoting cell proliferation while suppressing apoptosis and drug sensitivity.

Effects of opioid drugs on immune function in cancer patients.

Opioid receptor agonists are often used when cancer patients undergo surgery or analgesic treatment. As analgesics in clinical care, opioids can provide intraoperative or to chronic cancer pain relief. Immune function plays an important role in anti-cancer therapy, with cellular immunity, comprised principally of T-lymphocytes and natural killer cells, representing the primary anti-cancer immune response. However, it remains unclear whether immune function is further affected with the use of opioids in already immunocompromised cancer patients. This article provides a review of the effects of commonly used clinical opioids, including morphine, oxycodone, fentanyl and tramadol, on immune function in cancer patients. It provides a summary of current evidence regarding the immunomodulatory effects of opioids in the cancer setting and mechanisms underlying these interactions.

STAT3 activation of SCAP-SREBP-1 signaling upregulates fatty acid synthesis to promote tumor growth.

SCAP plays a central role in controlling lipid homeostasis by activating SREBP-1, a master transcription factor in controlling fatty acid (FA) synthesis. However, how SCAP expression is regulated in human cancer cells remains unknown. Here, we revealed that STAT3 binds to the promoter of SCAP to activate its expression across multiple cancer cell types. Moreover, we identified that STAT3 also concurrently interacts with the promoter of SREBF1 gene (encoding SREBP-1), amplifying its expression. This dual action by STAT3 collaboratively heightens FA synthesis. Pharmacological inhibition of STAT3 significantly reduces the levels of unsaturated FAs and phospholipids bearing unsaturated FA chains by reducing the SCAP-SREBP-1 signaling axis and its downstream effector SCD1. Examination of clinical samples from patients with glioblastoma, the most lethal brain tumor, demonstrates a substantial co-expression of STAT3, SCAP, SREBP-1, and SCD1. These findings unveil STAT3 directly regulates the expression of SCAP and SREBP-1 to promote FA synthesis, ultimately fueling tumor progression.

Revealing the Optimization Route of Piezoelectric Sonosensitizers: From Mechanism to Engineering Methods.

Piezoelectric catalysis is a novel catalytic technology that has developed rapidly in recent years and has attracted extensive interest among researchers in the field of tumor therapy for its acoustic-sensitizing properties. Nevertheless, researchers are still controversial about the key technical difficulties in the modulation of piezoelectric sonosensitizers for tumor therapy applications, which is undoubtedly a major obstacle to the performance modulation of piezoelectric sonosensitizers. Clarification of this challenge will be beneficial to the design and optimization of piezoelectric sonosensitizers in the future. Here, the authors start from the mechanism of piezoelectric catalysis and elaborate the mechanism and methods of defect engineering and phase engineering for the performance modulation of piezoelectric sonosensitizers based on the energy band theory. The combined therapeutic strategy of piezoelectric sonosensitizers with enzyme catalysis and immunotherapy is introduced. Finally, the challenges and prospects of piezoelectric sonosensitizers are highlighted. Hopefully, the explorations can guide researchers toward the optimization of piezoelectric sonosensitizers and can be applied in their own research.

Decoding the molecular landscape: A novel prognostic signature for uveal melanoma unveiled through programmed cell death-associated genes.

Uveal melanoma (UM) is a rare but aggressive malignant ocular tumor with a high metastatic potential and limited therapeutic options, currently lacking accurate prognostic predictors and effective individualized treatment strategies. Public databases were utilized to analyze the prognostic relevance of programmed cell death-related genes (PCDRGs) in UM transcriptomes and survival data. Consensus clustering and Lasso Cox regression analysis were performed for molecular subtyping and risk feature construction. The PCDRG-derived index (PCDI) was evaluated for its association with clinicopathological features, gene expression, drug sensitivity, and immune infiltration. A total of 369 prognostic PCDRGs were identified, which could cluster UM into 2 molecular subtypes with significant differences in prognosis and clinicopathological characteristics. Furthermore, a risk feature PCDI composed of 11 PCDRGs was constructed, capable of indicating prognosis in UM patients. Additionally, PCDI exhibited correlations with the sensitivity to 25 drugs and the infiltration of various immune cells. Enrichment analysis revealed that PCDI was associated with immune regulation-related biological processes and pathways. Finally, a nomogram for prognostic assessment of UM patients was developed based on PCDI and gender, demonstrating excellent performance. This study elucidated the potential value of PCDRGs in prognostic assessment for UM and developed a corresponding risk feature. However, further basic and clinical studies are warranted to validate the functions and mechanisms of PCDRGs in UM.

Effect of perioperative blood transfusion on complications and prognosis after radical gastrectomy in elderly patients: a retrospective study of 1,666 cases.

Background: Multiple studies have examined the effect of perioperative blood transfusion (BTF) on postoperative complications and the prognosis of gastric cancer patients, but the conclusions remain controversial, and few studies related to elderly patients are present. This study sought to examine the effect of perioperative BTF on postoperative complications and the prognosis of elderly patients who underwent radical gastrectomy. Methods: The clinical data of 1,666 elderly patients (aged ≥60 years) at Xijing Hospital from October 2013 to October 2021 were retrospectively analyzed. The patients were stratified into the perioperative BTF group and the perioperative non-BTF group. The clinicopathological characteristics, postoperative complications, and long-term prognoses of the patients were compared. Results: There were significant differences in terms of sex, tumor location, tumor size, gastrectomy range, tumor differentiation, T stage, N stage, tumor-node-metastasis (TNM) stage, preoperative anemia, and intraoperative blood loss between the two groups (P<0.05). The incidence of postoperative fever in the BTF group was significantly higher than that in the non-BTF group (31.6% vs. 15.4%, P<0.001), but there were no significant differences in the other complications between the two groups (P>0.05). The survival analysis showed that in stage III patients, the prognosis of the BTF group was inferior to that of the non-BTF group [the 3-year overall survival (OS) rates of the groups were 33.7% vs. 47.9% respectively, P<0.001], while there was no significant difference between the two groups among the stage I and stage II patients (P>0.05). There was no significant difference in the prognosis of patients with different transfusion times (preoperative/intraoperative/postoperative) (P>0.05). The multivariate analysis indicated that perioperative BTF was not an independent risk factor for prognosis in elderly patients with gastric cancer overall or elderly patients with gastric cancer in stage III (P>0.05). Conclusions: Perioperative BTF may elevate the incidence of fever but has no significant effect on other complications in elderly patients after radical gastrectomy. Perioperative BTF is not an independent risk factor affecting the postoperative prognosis of elderly patients with gastric cancer.

Characterization of extrachromosomal circular DNAs in plasma of patients with clear cell renal cell carcinoma.

BACKGROUND AND PURPOSE: Extrachromosomal circular DNAs (eccDNAs) have been recognized for their significant involvement in numerous biological processes. Nonetheless, the existence and molecular characteristics of eccDNA in the peripheral blood of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have not yet been reported. Our aim was to identify potentially marked plasma eccDNAs in ccRCC patients. METHODS AND MATERIALS: The detection of plasma eccDNA in ccRCC patients and healthy controls was performed using the Tn5-tagmentation and next-generation sequencing (NGS) method. Comparisons were made between ccRCC patients and healthy controls regarding the distribution of length, gene annotation, pattern of junctional nucleotide motif, and expression pattern of plasma eccDNA. RESULTS: We found 8,568 and 8,150 plasma eccDNAs in ccRCC patients and healthy controls, respectively. There were no statistical differences in the length distribution, gene annotation, and motif signature of plasma eccDNAs between the two groups. A total of 701 differentially expressed plasma eccDNAs were identified, and 25 plasma eccDNAs with potential diagnostic value for ccRCC have been successfully screened. These up-regulated plasma eccDNAs also be indicated to originate from the genomic region of the tumor-associated genes. CONCLUSION: This work demonstrates the characterization of plasma eccDNAs in ccRCC and suggests that the up-regulated plasma eccDNAs could be considered as a promising non-invasive biomarker in ccRCC.

miR-214-PTEN pathway is a potential mechanism for stress-induced immunosuppression affecting chicken immune response to avian influenza virus vaccine.

Stress-induced immunosuppression (SIIS) is one of common problems in the intensive poultry industry, affecting the effect of vaccine immunization and leading to high incidences of diseases. In this study, the expression characteristics and regulatory mechanisms of miR-214 in the processes of SIIS and its influence on the immune response to avian influenza virus (AIV) vaccine in chicken were explored. The qRT-PCR results showed that serum circulating miR-214 was significantly differentially expressed (especially on 2, 5, and 28 days post immunization (dpi)) in the processes, so had the potential as a molecular marker. MiR-214 expressions from multiple tissues were closely associated with the changes in circulating miR-214 expression levels. MiR-214-PTEN regulatory network was a potential key regulatory mechanism for the heart, bursa of Fabricius, and glandular stomach to participate in the process of SIIS affecting AIV immune response. This study can provide references for further understanding of stress affecting immune response.

Ruxolitinib Monotherapy for a Child With HAVCR2 Gene Mutation Associated Subcutaneous Panniculitis-Like T-Cell Lymphoma: A Case Report.

BACKGROUND: The occurrence of hemophagocytic lymphohistiocytosis (HLH) in patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) may be due to HAVCR2 gene mutation, leading to T-cell immunoglobulin and mucin domain-containing molecule 3 deficiency, T-cell and macrophage activation, and proinflammatory cytokine production. OBSERVATION: We report a patient with SPTCL and HLH for whom ruxolitinib, used as a novel treatment, showed notable therapeutic effects. CONCLUSIONS: Remission of both HAVCR2 mutation-induced high inflammatory characteristics and significant symptoms post-ruxolitinib administration suggested that patients with SPTCL and HLH may not represent typical lymphoma cases. Ruxolitinib, with its relatively low toxic side effects, can provide favorable outcomes.

Quantified difference of the collapsed cone convolution (CCC) and Monte Carlo (MC) algorithms based on DVH and gamma analysis for cervical cancer radiation therapy.

OBJECTIVE: To quantify the difference between the (collapsed cone convolution) CCC algorithm and the (Monte Carlo) MC algorithm and remind that the planners should pay attention to some possible uncertainties of the two algorithms when employing the two algorithms. METHODS: Thirty patients' cervical cancer VMAT plans were designed with a Pinnacle TPS (Philips) and divided equally into two groups: the simple group (SG, target volume was only the PTV) and the complex group (CG, target volume included the PTV and PGTV). The plans from the Pinnacle TPS were transferred to the Monaco TPS (Elekta). The plans' parameters all remained unchanged, and the dose was recalculated. Gamma passing rates (GPRs) obtained from dose distribution from Pinnacle TPS compared with that from Monaco TPS with SNC software based on three triaxial planes (transverse, sagittal and coronal). GPRs and DVH were used to quantify the difference between the CCC algorithm in pinnacle TPS and the MC algorithm in Monaco TPS. RESULTS: Among the statistical dose indexes in DVHs from the Pinnacle and Monaco TPSs, there were 7(7/15) dose indexes difference with statistically significant differences in the SG, and 10(10/18) dose indexes difference with statistically significant differences in the CG. With 3%/3 mm criterion, the most (5/6) GPRs were greater than 95% from the SG and CG. But with 2%/2 mm criterion, the most (5/6) GPRs were less than 90% from the two groups. In addition, we found that GPRs were also related to the selected triaxial planes and the complexity of the plan (GPRs varied with the SG and CG). CONCLUSIONS: Obvious difference between the CCC and MC algorithms from Pinnacle and Monaco TPS. DVH maybe better than 2D gamma analysis on quantifying difference of the CCC and MC algorithms. Some attention should be paid to the uncertainty of the TPS algorithm, especially when the indicator on the DVH is at the critical point of the threshold value, because the algorithm used may overestimate or underestimate the DVH indicator.

Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis.

CONTEXT.­: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. OBJECTIVE.­: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. DESIGN.­: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. RESULTS.­: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. CONCLUSIONS.­: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.