mNGS helped diagnose scrub typhus-associated HLH in children: a report of two cases.

Background: Scrub typhus, caused by the Orientia tsutsugamushi (Ot), is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar. Case presentation: We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen Orientia tsutsugamushi (Ot) was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly. Conclusion: The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches.

Feasible CT features to distinguish incidental rib enhancement from sclerotic metastasis in patients with malignancies.

OBJECTIVE: To investigate the CT features of incidental rib enhancement (RE) and to summarize the CT characteristics for distinguishing the RE from sclerotic metastasis (SM) in patients with malignancies. MATERIAL AND METHODS: This retrospective observational study enrolled 79 patients with RE (involved 133 ribs) during October 2014 and December 2021. Another 53 patients with SM (160 SM) in the same period were selected randomly for comparison. The location, enhancement patterns of RE were reviewed. The CT values of RE regions and SM were measured and statistically analyzed. RESULTS: Most REs (70 patients, 88.6%) were in the 1st to 6th ribs. 50 patients had solitary RE and 29 with multiple REs in a regional distribution. All the REs were closely connected to the intercostal venous plexus (ICVP) ipsilateral to the injection site. No visible abnormalities on unenhanced scans were detected in all REs. One hundred and twenty REs (90.2%) had nodular/patchy enhancement. The CT value of RE regions in the venous phase was lower than that in the arterial phase (589.8 ± 344.2 HU versus 1188.5 ± 325.3 HU, p < 0.001). During the venous phase, most REs (125, 94.0%) shrank or disappeared. SM appeared similar on both contrast-enhanced and unenhanced scans in terms of shape and CT values. CONCLUSION: The RE demonstrated characteristic CT features. The manifestations of nodular/patchy enhancement in the arterial phase, decreased density and shrinkage or disappearance during the venous phase, and no abnormality on unenhanced scans, as well as a close connection with the ICVP, may help differentiate RE from SM.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

Semi-automatic fine delineation scheme for pancreatic cancer.

BACKGROUND: Pancreatic cancer fine delineation in medical images by physicians is a major challenge due to the vast volume of medical images and the variability of patients. PURPOSE: A semi-automatic fine delineation scheme was designed to assist doctors in accurately and quickly delineating the cancer target region to improve the delineation accuracy of pancreatic cancer in computed tomography (CT) images and effectively reduce the workload of doctors. METHODS: A target delineation scheme in image blocks was also designed to provide more information for the deep learning delineation model. The start and end slices of the image block were manually delineated by physicians, and the cancer in the middle slices were accurately segmented using a three-dimensional Res U-Net model. Specifically, the input of the network is the CT image of the image block and the delineation of the cancer in the start and end slices, while the output of the network is the cancer area in the middle slices of the image block. Meanwhile, the model performance of pancreatic cancer delineation and the workload of doctors in different image block sizes were studied. RESULTS: We used 37 3D CT volumes for training, 11 volumes for validating and 11 volumes for testing. The influence of different image block sizes on doctors' workload was compared quantitatively. Experimental results showed that the physician's workload was minimal when the image block size was 5, and all cancer could be accurately delineated. The Dice similarity coefficient was 0.894 ± 0.029, the 95% Hausdorff distance was 3.465 ± 0.710 mm, the normalized surface Dice was 0.969 ± 0.019. By completing the accurate delineation of all the CT images, the speed of the new method is 2.16 times faster than that of manual sketching. CONCLUSION: Our proposed 3D semi-automatic delineative method based on the idea of block prediction could accurately delineate CT images of pancreatic cancer and effectively deal with the challenges of class imbalance, background distractions, and non-rigid geometrical features. This study had a significant advantage in reducing doctors' workload, and was expected to help doctors improve their work efficiency in clinical application.

Bioactive compound composition and cellular antioxidant activity of fig (Ficus carica L.).

BACKGROUND: Fig (Ficus carica L.) fruit is consumed worldwide as a functional food. It contains phytochemicals that have been related to health benefits. However, the characteristic chemicals remain unclear. In this work, phytochemicals were prepared from figus by ultrasound-assisted extraction under optimized conditions. The chemical composition of fig fruit and leaves was characterized by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: One hundred and fifty-seven compounds were identified, including 58 flavonoids, 29 coumarins, 19 acids, 15 terpenoids, 11 alkaloids, and 25 other compounds. The mass spectrum (MS) fragmentation pathways of representative chemicals were elucidated. Flavonoid glycosides and prenylated flavonoids were mainly present in fig fruit, whereas coumarins were abundant in leaves. Both fig fruit and leaf extracts showed good cellular antioxidant activity. CONCLUSION: The full phytochemical profile of fig was revealed by UPLC-MS/MS. Prenylated flavonoids and prenylated coumarins were the characteristic phytochemicals. These data provided useful information for the extensive utilization of fig fruit in functional food. © 2023 Society of Chemical Industry.

A primary pediatric acute myelomonocytic leukemia with t(3;21)(q26;q22): A case report.

RATIONALE: The rare t(3;21)(q26;q22) translocation results in gene fusion and generates multiple fusion transcripts, which are typically associated with therapy-related myelodysplastic syndrome, acute myeloid leukemia, and chronic myelogenous leukemia. Here, we report a rare case of de novo acute myelomonocytic leukemia in a young child with t(3;21)(q26;q22). PATIENT CONCERNS: A 2-and-a-half-year-old female patient presented with abdominal pain, cough, paleness, and fever for 3 weeks, without any history of malignant diseases. DIAGNOSES: Chest computed tomography revealed pneumonia. Bone marrow smear confirmed acute myelomonocytic leukemia. Cytogenetic analysis and Sanger sequencing identified RUNX1-MECOM and RUNX1-RPL22 fusion genes as a result of t(3;21)(q26;q22). INTERVENTIONS: The patient received 3 courses of chemotherapy, but bone marrow smear examination showed no remission. According to the wishes of the patient family, the allogeneic hematopoietic stem cell transplantation (Allo-HSCT) was chosen. OUTCOMES: The patient did not experience any adverse reactions after Allo-HSCT. The red blood cells and platelets increased without transfusion. The pneumonia recovered after antibiotic treatment. LESSONS: The patient recovered well after Allo-HSCT. Therefore, for patients with RUNX1-MECOM and RUNX1-RPL22 fusion genes, transplantation may be a good choice when chemotherapy is not effective.

Molecular epidemiology and clinical characteristics of enteroviruses associated HFMD in Chengdu, China, 2013-2022.

OBJECTIVES: This study aims to investigate molecular epidemiology and clinical characteristics of enterovirus associated hand-foot-mouth disease (HFMD) in Chengdu, China, 2013-2022. Monitoring the molecular epidemiology and clinical features of HFMD for up to 10 years may provide some ideas for future protection and control measures. METHODS: We conducted a retrospective analysis of the medical records of all patients with laboratory-confirmed HFMD-related enterovirus infection at the West China Second University Hospital from January 2013 to December 2022. We described the characteristics in serotype, age, sex distribution and hospitalization of enterovirus infection cases using data analysis and graphic description. RESULTS: A total of 29,861 laboratory-confirmed cases of HFMD-related enterovirus infection were reported from 2013 to 2022. There was a significant reduction in the number and proportion of EV-A71 cases after 2016, from 1713 cases (13.60%) in 2013-2015 to 150 cases (1.83%) in 2017-2019. During the COVID-19 pandemic, EV-A71 cases even disappeared. The proportion of CV-A16 cases decreased from 13.96% in 2013-2015 to 10.84% in 2017-2019 and then to 4.54% in 2020-2022. Other (non-EV-A71 and non-CV-A16) serotypes accounted for 95.45% during 2020-2022, with CV-A6 accounting for 50.39% and CV-A10 accounting for 10.81%. Thus, CV-A6 and CV-A10 became the main prevalent serotypes. Furthermore, There was no significant difference in the enterovirus prevalence rate between males and females. The hospitalization rate of EV-A71 patients was higher that of other serotypes. In general, the proportion of HFMD hospitalizations caused by other pathogens except for EV-A71, CV-A16, CV-A10 and CV-A16 was second only to that caused by EV-A71. The proportion of children over 4 years old infected with enterovirus increased. CONCLUSION: The incidence of HFMD associated with enterovirus infection has decreased significantly and CV-A6 has been the main pathogen of HFMD in Chengdu area in recent years. The potential for additional hospitalizations for other untested enterovirus serotypes suggested that attention should also be paid to the harms of infections with unknown enterovirus serotypes. Children with HFMD were older. The development of new diagnostic reagents and vaccines may play an important role in the prevention and control of enterovirus infection.

Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers.

Enhanced recognition ability, cell uptake capacity, and biostability are characteristics attributed to aptamer-based targeted anticancer agents, and are possibly associated with increased accumulation at the tumor site, improved therapeutic efficacy and reduced negative side effects. Herein, a phosphorothioate backbone modification strategy was applied to regulate the biomedical properties of pancreatic cancer cell-targeting aptamer for efficient in vivo drug delivery. Specifically, the CD71- targeting aptamer XQ-2d was modified into a fully thio-substituted aptamer S-XQ-2d, improving the plasma stability of S-XQ-2d and mitomycin C (MMC)-functionalized S-XQ-2d (MFSX), thus considerably prolonging their half-life in mice. Moreover, the binding and uptake capacities of S-XQ-2d were significantly enhanced. MFSX showed the same level of cytotoxicity as that of MMC against targeted cancer cells, but lower toxicity to non-targeted cells, highlighting its specificity and biosafety. Brief mechanistic studies demonstrated that XQ-2d and S-XQ-2d had different interaction modes and internalization pathways with the targeted cells.

Leishmania donovani visceral leishmaniasis diagnosed by metagenomics next-generation sequencing in an infant with acute lymphoblastic leukemia: a case report.

Background: Visceral leishmaniasis (VL) is a neglected vector-borne tropical disease caused by Leishmania donovani (L. donovani) and Leishmania infantum (L. infantum). Due to the very small dimensions of the protozoa impounded within blood cells and reticuloendothelial structure, diagnosing VL remains challenging. Case presentation: Herein, we reported a case of VL in a 17-month-old boy with acute lymphoblastic leukemia (ALL). The patient was admitted to West China Second University Hospital, Sichuan University, due to repeated fever after chemotherapy. After admission, chemotherapy-related bone marrow suppression and infection were suspected based on clinical symptoms and laboratory test results. However, there was no growth in the conventional peripheral blood culture, and the patient was unresponsive to routine antibiotics. Metagenomics next-generation sequencing (mNGS) of peripheral blood identified 196123 L. donovani reads, followed by Leishmania spp amastigotes using cytomorphology examination of the bone marrow specimen. The patient was given pentavalent antimonials as parasite-resistant therapy for 10 days. After the initial treatment, 356 L. donovani reads were still found in peripheral blood by mNGS. Subsequently, the anti-leishmanial drug amphotericin B was administrated as rescue therapy, and the patient was discharged after a clinical cure. Conclusion: Our results indicated that leishmaniasis still exists in China. Unbiased mNGS provided a clinically actionable diagnosis of a specific infectious disease from an uncommon pathogen that eluded conventional testing.

The landscape of objective response rate of anti-PD-1/L1 monotherapy across 31 types of cancer: a system review and novel biomarker investigating.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of cancer treatment. However, only a few patients respond to ICI treatment. Thus, uncovering clinically accessible ICI biomarkers would help identify which patients will respond well to ICI treatment. A comprehensive objective response rate (ORR) data of anti-PD-1/PD-L1 monotherapy in pan-cancer would offer the original data to explore the new biomarkers for ICIs. METHODS: We systematically searched PubMed, Cochrane, and Embase for clinical trials on July 1, 2021, limited to the years 2017-2021, from which we obtained studies centering around anti-PD-1/PD-L1 monotherapy. Finally, 121 out of 3099 publications and 143 ORR data were included. All of the 31 tumor types/subtypes can be found in the TCGA database. The gene expression profiles and mutation data were downloaded from TCGA. A comprehensive genome-wide screening of ORR highly correlated mutations among 31 cancers was conducted by Pearson correlation analysis based on the TCGA database. RESULTS: According to the ORR, we classified 31 types of cancer into high, medium, and low response types. Further analysis uncovered that "high response" cancers had more T cell infiltration, more neoantigens, and less M2 macrophage infiltration. A panel of 28 biomarkers reviewed from recent articles were investigated with ORR. We also found the TMB as a traditional biomarker had a high correlation coefficient with ORR in pan-cancer, however, the correlation between ITH and ORR was low across pan-cancer. Moreover, we primarily identified 1044 ORR highly correlated mutations through a comprehensive screening of TCGA data, among which USH2A, ZFHX4 and PLCO mutations were found to be highly correlated to strengthened tumor immunogenicity and inflamed antitumor immunity, as well as improved outcomes for ICIs treatment among multiple immunotherapy cohorts. CONCLUSION: Our study provides comprehensive data on ORR of anti-PD-1/PD-L1 monotherapy across 31 tumor types/subtypes and an essential reference of ORR to explore new biomarkers. We also screened out a list of 1044 immune response related genes and we showed that USH2A, ZFHX4 and PLCO mutations may act as good biomarkers for predicting patient response to anti-PD-1/PD-L1 ICIs.

Serum Amyloid a Predicts Prognosis and Chemotherapy Efficacy in Patients with Advanced Pancreatic Cancer.

Purpose: There is an urgent need to discover a predictive biomarker to help patients with advanced pancreatic cancer (APC) choose appropriate chemotherapy regimens. This study aimed to determine whether baseline serum amyloid A (SAA) levels were associated with overall survival (OS), progression-free survival (PFS), and treatment response in patients with APC received chemotherapy. Patients and Methods: This retrospective study included 268 patients with APC who received first-line chemotherapy at the Sun Yat-Sen University Cancer Center between January 2017 and December 2021. We examined the effect of baseline SAA on OS, PFS and chemotherapy response. The X-Tile program was used to determine the critical value for optimizing the significance of segmentation between Kaplan-Meier survival curves. The Kaplan-Meier curves and Cox regression analyses were used to analyze OS and PFS. Results: The best cut-off value of baseline SAA levels for OS stratification was 8.2 mg/L. Multivariate analyses showed that SAA was an independent predictor of OS (Hazard Ratio (HR) = 1.694, 95% Confidence Interval (CI) = 1.247-2.301, p = 0.001) and PFS (HR = 1.555, 95% CI = 1.152-2.098, p = 0.004). Low SAA was associated with longer OS (median, 15.7 months vs 10.0 months, p < 0.001) and PFS (median, 7.6 months vs 4.8 months, p < 0.001). The patients with a low SAA who received mFOLFIRINOX had longer OS (median, 28.5 months vs 15.1 months, p = 0.019) and PFS (median, 12.0 months vs 7.4 months, p = 0.035) than those who received nab-paclitaxel plus gemcitabine (AG) or SOXIRI, whereas there was no significant difference among the three chemotherapy regimens in patients with a high SAA. Conclusion: Owing to the rapid and simple analysis of peripheral blood, baseline SAA might be a useful clinical biomarker, not only as a prognostic biomarker for patients with APC, but also as a guide for the selection of chemotherapy regimens.

Response evaluation of hepatocellular carcinoma treated with stereotactic body radiation therapy: magnetic resonance imaging findings.

PURPOSE: To summarize the magnetic resonance imaging manifestations of hepatocellular carcinoma (HCC) with and without progression after stereotactic body radiation therapy (SBRT) and evaluate the treatment effect using the modified Liver Reporting and Data System (LI-RADS). METHODS: Between January 2015 and December 2020, 102 patients with SBRT-treated HCC were included. Tumor size, signal intensity, and enhancement patterns at each follow-up period were analyzed. Three different patterns of enhancement: APHE and wash-out, non-enhancement, and delayed enhancement. For modified LI-RADS, delayed enhancement with no size increase were considered to be a "treatment-specific expected enhancement pattern" for LR-TR non-viable. RESULTS: Patients were divided into two groups: without (n = 96) and with local progression (n = 6). Among patients without local progression, APHE and wash-out pattern demonstrated conversion to the delayed enhancement (71.9%) and non-enhancement (20.8%) patterns, with decreased signal intensity on T1WI(92.9%) and DWI(99%), increased signal intensity on T1WI (99%), and decreased size. The signal intensity and enhancement patterns stabilized after 6-9 months. Six cases with progression exhibited tumor growth, APHE and wash-out, and increased signal intensity on T2WI/DWI. Based on the modified LI-RADS criteria, 74% and 95% showed LR-TR-nonviable in 3 and 12 months post-SBRT, respectively. CONCLUSIONS: After SBRT, the signal intensity and enhancement patterns of HCCs showed a temporal evolution. Tumor growth, APHE and wash-out, and increased signal intensity on T2WI/DWI indicates tumor progression. Modified LI-RADS criteria showed good performance in evaluating nonviable lesions after SBRT.

Multi-parameter Inputted Logic-Gating on Aptamer-Encoded Extracellular Vesicles for Colorectal Cancer Diagnosis.

Extracellular vesicles (EVs) have emerged as a potential biomarker in liquid biopsy. However, cancer heterogeneity poses significant challenge to precise molecular diagnosis based on single-parameter input. Hence, strategies for analyzing multiple inputs with molecular computing were developed with the aim of improving diagnostic accuracy in liquid biopsy. In the present study, based on the surface of aptamer-encoded EVs, three toe-hold extended DNA aptamers served as specific inputs to perform AND-logic-gating to distinguish between healthy and cancerous EVs. In addition, this strategy has been successfully employed to analyze circulating EVs in clinical samples from colorectal cancer patients and healthy donors. The developed method has a promising future in the analysis of multiplex EV membrane proteins and the identification of early cancer.

Radiomic Signatures for Predicting Receptor Status in Breast Cancer Brain Metastases.

Backgrounds: A significant proportion of breast cancer patients showed receptor discordance between primary cancers and breast cancer brain metastases (BCBM), which significantly affected therapeutic decision-making. But it was not always feasible to obtain BCBM tissues. The aim of the present study was to analyze the receptor status of primary breast cancer and matched brain metastases and establish radiomic signatures to predict the receptor status of BCBM. Methods: The receptor status of 80 matched primary breast cancers and resected brain metastases were retrospectively analyzed. Radiomic features were extracted using preoperative brain MRI (contrast-enhanced T1-weighted imaging, T2-weighted imaging, T2 fluid-attenuated inversion recovery, and combinations of these sequences) collected from 68 patients (45 and 23 for training and test sets, respectively) with BCBM excision. Using least absolute shrinkage selection operator and logistic regression model, the machine learning-based radiomic signatures were constructed to predict the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of BCBM. Results: Discordance between the primary cancer and BCBM was found in 51.3% of patients, with 27.5%, 27.5%, and 5.0% discordance for ER, PR, and HER2, respectively. Loss of receptor expression was more common (33.8%) than gain (18.8%). The radiomic signatures built using combination sequences had the best performance in the training and test sets. The combination model yielded AUCs of 0.89, 0.88, and 0.87, classification sensitivities of 71.4%, 90%, and 87.5%, specificities of 81.2%, 76.9%, and 71.4%, and accuracies of 78.3%, 82.6%, and 82.6% for ER, PR, and HER2, respectively, in the test set. Conclusions: Receptor conversion in BCBM was common, and radiomic signatures show potential for noninvasively predicting BCBM receptor status.

Mycoplasma genitalium and Chlamydia trachomatis infection among women in Southwest China: a retrospective study.

Mycoplasma genitalium (MG) and Chlamydia trachomatis (CT) are the most common sexually transmitted pathogens, which can cause cervicitis, pelvic inflammation and infertility in female. In the present study, we collected the basic information, clinical results of leucorrhoea and human papillomavirus (HPV) infection of patients, who were involved in both MG and CT RNA detection in West China Second Hospital of Sichuan University from January 2019 to April 2021, ranging from 18 to 50 years old. The results showed that the infection frequencies of MG and CT were 2.6% and 6.5%, respectively. The infection rate of CT in gynaecological patients was significantly higher than that of MG (P < 0.001). Moreover, patients with CT infection often had symptoms of gynaecological diseases, while patients with MG infection remain often asymptomatic. By exploring the connection between MG or CT infection and vaginal secretions, we found that the infection of MG or CT promoted to the increase of vaginal leukocytes, and CT infection exacerbated the decrease of the number of Lactobacillus in the vagina. Further analysis suggested that independent infection and co-infection of MG or CT resulted in abnormal vaginal secretion, affecting the stability of vaginal environment, which may induce vaginal diseases. Unexpectedly, our study found no association between MG or CT infection and high-risk HPV infection. In conclusion, our study explored the infection of MG and CT among women in Southwest China for the first time, and revealed that the infection of MG or CT would affect the homeostasis of vaginal environment, which laid a foundation for the clinical diagnosis and treatment of MG and CT infection.

The growth pattern of liver metastases on MRI predicts early recurrence in patients with colorectal cancer: a multicenter study.

OBJECTIVES: The multicenter study aimed to explore the relationship between the growth pattern of liver metastases on preoperative MRI and early recurrence in patients with colorectal cancer liver metastases (CRCLM) after surgery. METHODS: A total of 348 CRCLM patients from 3 independent centers were enrolled, including 130 patients with 339 liver metastases in the primary cohort and 218 patients in validation cohorts. Referring to the gross classification of hepatocellular carcinoma (HCC), the growth pattern of each liver metastasis on MRI was classified into four types: rough, smooth, focal extranodular protuberant (FEP), and nodular confluent (NC). Disease-free survival (DFS) curve was constructed using the Kaplan-Meier method. RESULTS: In primary cohort, 42 (12.4%) of the 339 liver metastases were rough type, 237 (69.9%) were smooth type, 29 (8.6%) were FEP type, and 31 (9.1%) were NC type. Those patients with FEP- and/or NC-type liver metastases had shorter DFS than those without such metastases (p < 0.05). However, there were no significant differences in DFS between patients with rough- and smooth-type liver metastases and those without such metastases. The patients with FEP- and/or NC-type liver metastases also had shorter DFS than those without such metastases in two external validation cohorts. In addition, 40.5% of high-risk-type (FEP and NC) liver metastases converted to low-risk types (rough and smooth) after neoadjuvant chemotherapy. CONCLUSION: The FEP- and NC-type liver metastases were associated with early recurrence, which may facilitate the clinical treatment of CRCLM patients. KEY POINTS: • In the primary cohort, patients with FEP- and NC-type metastases had shorter disease-free survival (DFS) and a higher intrahepatic recurrence rate than patients without such metastases in the liver. • In the primary cohort, there were no significant differences in DFS or intrahepatic recurrence rate between patients with rough- and smooth-type metastases and those without such metastases in the liver. • High-risk patients had shorter DFS and a higher intrahepatic recurrence rate than low-risk patients in primary and external validation cohorts.

Identifying Outcomes of Patients With Advanced Pancreatic Adenocarcinoma and RECIST Stable Disease Using Radiomics Analysis.

PURPOSE: Few studies have explored the biomarkers for predicting the heterogeneous outcomes of patients with advanced pancreatic adenocarcinoma showing stable disease (SD) on the initial postchemotherapy computed tomography. We aimed to devise a radiomics signature (RS) to predict these outcomes for further risk stratification. MATERIALS AND METHODS: Patients with advanced pancreatic adenocarcinoma and SD after chemotherapy were included. Pancreatic lesions on initial postchemotherapy computed tomography images were evaluated by radiomics analysis for predicting early death (≤ 1 year). RS was then internally and externally tested. The progression-free survival and objective response rate were compared between the low-risk and high-risk group of patients classified following RS. RESULTS: Approximately 62.7% of patients receiving chemotherapy showed SD at first response evaluation in the primary cohort, which were 59.6% and 57.9% in internal and external testing cohorts, respectively. The RS predicted 1-year overall survival well, with areas under the receiver operating characteristic curve of 0.91 in the training cohort, 0.90 in the validation cohort, 0.84 in the internal testing cohort, and 0.87 in the external testing cohort. The high-risk group had a shorter median progression-free survival (7.3 months v 9.0 months, P = .016, in the training cohort; 5.9 months v 9.2 months, P = .026, in the internal testing cohort) and a lower objective response rate (2.2% v 24.0% in the training cohort) than the low-risk group. In addition, RS was not related to the clinical characteristics and chemotherapy regimens. CONCLUSION: RS independently predicts the outcomes of patients with SD after chemotherapy well and can help to improve treatment decisions by identifying patients for whom current treatment may not be suitable.

Five New Species of the Lichen-Forming Fungal Genus Peltula from China.

The genus Peltula is an important cyanobacterial lichen group. We performed a taxonomic study on the Peltula from China using phylogenetic analysis based on three gene loci (ITS, nuSSU, nuLSU) together with additional species delimitation analyses by ABGD, bPTP and GMYC approaches and the phenotypic characteristics. Five new species (Peltula lobulata, P. polycarpa, P. polyphylla, P. pseudoboletiformis and P. submarginata) were found and described. Peltula lobulata is diagnostic in its small thallus with plenty of lobules, rolled down and irregularly lobed margins, and uneven cracked surfaces. Peltula polycarpa has convex and rolled down lobes and numerous apothecia with a thalloid rim covering the whole lobe, and it can be distinguished from fertile P. farinosa (southern Switzerland) by a bright olive-green and epruinose surface, and the absence of isidia. Peltula polyphylla is differentiated from any other known Peltula species by a very small polyphyllous thallus composed of abundant olive-brown to olive-black small lobes growing tightly and sometimes anastomosing and attaching to the substrate by a large and strong umbilical cluster. Peltula submarginata is similar to P. marginata but differs in the presence of encircled epinecral and algae layers, and the absence of a lower cortex. Peltula pseudoboletiformis is different from the similar species P. boletiformis in greener lobes, more yellow-green umbilici and certain phylogenetic differences. Moreover, a key to the species of Peltula in China is also provided here.

Development and validation of a deep-learning model for detecting brain metastases on 3D post-contrast MRI: a multi-center multi-reader evaluation study.

BACKGROUND: Accurate detection is essential for brain metastasis (BM) management, but manual identification is laborious. This study developed, validated, and evaluated a BM detection (BMD) system. METHODS: Five hundred seventy-three consecutive patients (10 448 lesions) with newly diagnosed BMs and 377 patients without BMs were retrospectively enrolled to develop a multi-scale cascaded convolutional network using 3D-enhanced T1-weighted MR images. BMD was validated using a prospective validation set comprising an internal set (46 patients with 349 lesions; 44 patients without BMs) and three external sets (102 patients with 717 lesions; 108 patients without BMs). The lesion-based detection sensitivity and the number of false positives (FPs) per patient were analyzed. The detection sensitivity and reading time of three trainees and three experienced radiologists from three hospitals were evaluated using the validation set. RESULTS: The detection sensitivity and FPs were 95.8% and 0.39 in the test set, 96.0% and 0.27 in the internal validation set, and ranged from 88.9% to 95.5% and 0.29 to 0.66 in the external sets. The BMD system achieved higher detection sensitivity (93.2% [95% CI, 91.6-94.7%]) than all radiologists without BMD (ranging from 68.5% [95% CI, 65.7-71.3%] to 80.4% [95% CI, 78.0-82.8%], all P < .001). Radiologist detection sensitivity improved with BMD, reaching 92.7% to 95.0%. The mean reading time was reduced by 47% for trainees and 32% for experienced radiologists assisted by BMD relative to that without BMD. CONCLUSIONS: BMD enables accurate BM detection. Reading with BMD improves radiologists' detection sensitivity and reduces their reading times.