The significance of an immunohistochemical marker-based panel in assisting the diagnosis of parathyroid carcinoma.

PURPOSE: Parathyroid carcinoma (PC) is an endocrine malignancy with a poor prognosis. However, the diagnosis of PC is still a difficult problem. A model with immunohistochemical (IHC) staining of 5 biomarkers has been reported from limited samples for the differential diagnosis of PC. In the present study, a series of IHC markers was applied in relatively large samples to optimize the diagnostic model for PC. METHODS: In this study, 44 patients with PC, 6 patients with atypical parathyroid tumors and 57 patients with parathyroid adenomas were included. IHC staining for parafibromin, Ki-67, galectin-3, protein-encoding gene product 9.5 (PGP9.5), E-cadherin, and enhancer of zeste homolog 2 (EZH2) was performed on formalin-fixed, paraffin-embedded tissue samples. The effects of clinical characteristics, surgical procedure, and IHC staining results of tumor tissues on the diagnosis and prognosis of PC were evaluated retrospectively. RESULTS: A logistic regression model with IHC results of parafibromin, Ki-67, and E-cadherin was created to differentiate PC with an area under the curve of 0.843. Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio: 3.26, 95% confidence interval: 1.28-8.34, P = 0.013) was related to the recurrence of PC. CONCLUSION: An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish PC from parathyroid neoplasms. Among the 6 IHC markers and clinical features examined, the risk factor related to PC recurrence was parafibromin staining loss.

Modulating ferroptosis sensitivity: environmental and cellular targets within the tumor microenvironment.

Ferroptosis, a novel form of cell death triggered by iron-dependent phospholipid peroxidation, presents significant therapeutic potential across diverse cancer types. Central to cellular metabolism, the metabolic pathways associated with ferroptosis are discernible in both cancerous and immune cells. This review begins by delving into the intricate reciprocal regulation of ferroptosis between cancer and immune cells. It subsequently details how factors within the tumor microenvironment (TME) such as nutrient scarcity, hypoxia, and cellular density modulate ferroptosis sensitivity. We conclude by offering a comprehensive examination of distinct immunophenotypes and environmental and metabolic targets geared towards enhancing ferroptosis responsiveness within the TME. In sum, tailoring precise ferroptosis interventions and combination strategies to suit the unique TME of specific cancers may herald improved patient outcomes.

Advanced insights on tumor-associated macrophages revealed by single-cell RNA sequencing: The intratumor heterogeneity, functional phenotypes, and cellular interactions.

Single-cell RNA sequencing (scRNA-seq) is an emerging technology used for cellular transcriptome analysis. The application of scRNA-seq has led to profoundly advanced oncology research, continuously optimizing novel therapeutic strategies. Intratumor heterogeneity extensively consists of all tumor components, contributing to different tumor behaviors and treatment responses. Tumor-associated macrophages (TAMs), the core immune cells linking innate and adaptive immunity, play significant roles in tumor progression and resistance to therapies. Moreover, dynamic changes occur in TAM phenotypes and functions subject to the regulation of the tumor microenvironment. The heterogeneity of TAMs corresponding to the state of the tumor microenvironment has been comprehensively recognized using scRNA-seq. Herein, we reviewed recent research and summarized variations in TAM phenotypes and functions from a developmental perspective to better understand the significance of TAMs in the tumor microenvironment.

Localization of Ectopic Hyperparathyroidism: Ultrasound Versus 99mTc-sestamibi, 4-Dimensional Computed Tomography, and 11C-choline Positron Emission Tomography/Computed Tomography.

OBJECTIVE: To investigate the usefulness of ultrasound (US) for the localization of ectopic hyperparathyroidism and compare it with 99mTc-sestamibi (99mTc-MIBI), 4-dimensional computed tomography (4D-CT), and 11C-choline positron emission tomography/ computed tomography (PET/CT). METHODS: Of the 527 patients with surgically confirmed primary hyperparathyroidism, 79 patients with ectopic hyperparathyroidism were enrolled. The diagnostic performance of US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT was calculated, and the factors affecting the sensitivity of US and 99mTc-MIBI were analyzed. RESULTS: Eighty-three ectopic parathyroid lesions were found in 79 patients. The sensitivity was 75.9%, 81.7%, 95.1%, 83.3%, and 100% for US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT, respectively. The difference in sensitivity among these different modalities did not achieve statistical significance (P > .05). The US sensitivity was significantly higher for ectopic lesions in the neck region than for those in the anterior mediastinum/chest wall (85.9% vs. 42.1%, P < .001). The 99mTc-MIBI and 4D-CT sensitivity was not significantly different between these two groups (84.1% vs. 94.6%, P = .193 and 81.3% vs. 85.7%, P = 1). The 11C-choline PET/CT sensitivity was 100% in both groups. CONCLUSIONS: US is a valuable tool for the localization of ectopic hyperparathyroidism, especially for ectopic lesions in the neck region.

A new prognostic model for glioblastoma multiforme based on coagulation-related genes.

Background: Glioblastoma multiforme (GBM) is the most aggressive, common, and lethal type of primary brain tumor. Multiple cancers have been associated with abnormalities in the coagulation system that facilitate tumor invasion and metastasis. In GBM, the prognostic value and underlying mechanism of coagulation-related genes (CRGs) have not been explored. Methods: RNA sequencing (RNA-seq) and clinical information on GBM were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), respectively. Following the identification of differentially expressed CRGs (DECRGs) between GBM and control samples, the survival-related DECRGs were selected via univariate and multivariate Cox regression analyses to establish a prognostic signature. The prognostic performance and clinical utility of the prognostic signature were assessed by the Kaplan-Meier (KM) analysis and receiver operating characteristic (ROC) curve analysis, and a nomogram was constructed. The signature genes-related underlying mechanisms were analyzed according to gene set enrichment analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-cell analysis. Finally, the difference in immune cell infiltration, stromal score, immune score, and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) score were compared between different risk groups. Results: A 5-gene prognostic signature (PLAUR, GP6, C5AR1, SERPINA5, F2RL2) was established for overall survival (OS) prediction of GBM patients. The predicted efficiency of the prognostic signature was confirmed in TGGA-GBM dataset and validated in the CGGA-GBM dataset, revealing that it could differentiate GBM patients from controls well, and high risk score was accompanied with poor prognosis. Moreover, biological process (BP) and signaling pathway analyses showed that signature genes were mainly enriched in the functions of blood coagulation and tumor invasion and metastasis. Moreover, high-risk patients exhibited higher levels of immune cell infiltration, stromal score, immune score, and ESTIMATE score than that of low-risk patients. Conclusions: An analysis of coagulation-related prognostic signatures was conducted in this study, as well as how signature genes may affect GBM progress, providing information that might provide new ideas for the development of GBM-related molecular targeted therapies.

Identification of potential therapeutic drugs targeting core genes for systemic lupus erythematosus (SLE) and coexisting COVID-19: Insights from bioinformatic analyses.

OBJECTIVE: Systemic lupus erythematosus (SLE) patients are at risk during the COVID-19 pandemic, yet the underlying molecular mechanisms remain incompletely understood. This study sought to analyze the potential molecular connections between COVID-19 and SLE, employing a bioinformatics approach to identify effective drugs for both conditions. METHODS: The data sets GSE100163 and GSE183071 were utilized to determine share differentially expressed genes (DEGs). These DEGs were later analyzed by various bioinformatic methods, including functional enrichment, protein-protein interaction (PPI) network analysis, regulatory network construction, and gene-drug interaction construction. RESULTS: A total of 50 common DEGs were found between COVID-19 and SLE. Gene ontology (GO) functional annotation revealed that "immune response," "innate immune response," "plasma membrane," and "protein binding" were most enriched in. Additionally, the pathways that were enriched include "Th1 and Th2 cell differentiation." The study identified 48 genes/nodes enriched with 292 edges in the PPI network, of which the top 10 hub genes were CD4, IL7R, CD3E, CD5, CD247, KLRB1, CD40LG, CD7, CR2, and GZMK. Furthermore, the study found 48 transcription factors and 8 microRNAs regulating these hub genes. Finally, four drugs namely ibalizumab (targeted to CD4), blinatumomab (targeted to CD3E), muromonab-CD3 (targeted to CD3E), and catumaxomab (targeted to CD3E) were found in gene-drug interaction. CONCLUSION: Four possible drugs that targeted two specific genes, which may be beneficial for COVID-19 patients with SLE.

Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm.

Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is crucial for improving prognosis; however, current diagnostic methods are insufficient for accurately identifying malignant PCNs. Here, we utilized mass spectrometry (MS)-based glycosite- and glycoform-specific glycoproteomics, combined with proteomics, to explore potential cyst fluid diagnostic biomarkers for PCN. The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated, and its characteristics during the malignant transformation of PCN were analyzed. Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN, a group of cyst fluid glycoprotein biomarkers was identified. Through parallel reaction monitoring (PRM)-based targeted glycoproteomic analysis, we validated these chosen glycoprotein biomarkers in a second cohort, ultimately confirming N-glycosylated PHKB (Asn-935, H5N2F0S0; Asn-935, H4N4F0S0; Asn-935, H5N4F0S0), CEACAM5 (Asn-197, H5N4F0S0) and ATP6V0A4 (Asn-367, H6N4F0S0) as promising diagnostic biomarkers for distinguishing malignant PCNs. These glycoprotein biomarkers exhibited robust performance, with an area under the curve ranging from 0.771 to 0.948. In conclusion, we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN. These findings hold significant clinical implications, providing valuable insights for PCN decision-making, and potentially offering therapeutic targets for PCN treatment.

Local resection for solid pseudopapillary neoplasms of the pancreas shows improved postoperative gastrointestinal function and reduced mental stress: a multiquestionnaire survey from a large cohort.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, low-grade malignant pancreatic tumor with a highly favorable prognosis. Most SPN patients are young and middle-aged women. The main controversial topic for SPN is local resection (LR) versus radical resection (RR). Theoretically, LR could lead to better gastrointestinal function (GIF) and less mental stress. However, no data is available to support this hypothesis. METHODS: All SPN patients undergoing surgical treatment in Peking Union Medical College Hospital from 2001 to 2021 were included in the study. A cross-sectional online multiquestionnaire survey containing 110 questions was sent to them (Clinicaltrial.org, NCT05604716). This online multiquestionnaire survey focused on GIF and mental stress and consisted of eight questionnaires. Multiple linear regression analysis was conducted to identify independent factors impacting GIF and mental stress. RESULTS: A total of 183 cases provided valid results. Among them, 46 patients (25.1%) underwent LR, and 137 (74.9%) underwent RR. Ninety-four cases (51.4%) underwent minimally invasive surgery (MIS), while 89 (48.6%) underwent open surgery. The average GSRS score of the patients was 1.9±0.7, indicating that most suffered from mild gastrointestinal dysfunction. The scores of PHQ-9 and GAD-7 in 16 patients (8.7%) and 27 (14.8%) patients, respectively, were beyond 10.0, which indicated clinical depression and anxiety. Additionally, 19 (10.4%) patients reported poor ability to work, and 31(16.9%) patients had significant body image concerns. Compared to other clinicopathological characteristics, LR (LR vs. RR: PHQ-9 score, P =0.018; WAI average score, P =0.010; EORTC QLQ-C30, nine subdomains, P <0.05; GSRS average score, P =0.006) and MIS (MIS vs. open surgery: EORTC QLQ-C30, three subdomains, P <0.05; GSRS average score, P =0.006) were the most significant factors predicting improved GIF and reduced mental stress. CONCLUSIONS: This study systematically presents postoperative GIF and mental stress of SPN patients using validated multiquestionnaires for the first time. It provides solid evidence that LR and MIS can improve GIF and reduce mental stress after surgery for SPN patients, which could be helpful for the surgeons to make more personalized surgical plans for their patients.

miR-3133 inhibits gastrointestinal cancer progression through activation of Hippo and p53 signalling pathways via multi-targets.

BACKGROUND: Malignant cell growth and chemoresistance, the main obstacles in treating gastrointestinal cancer (GIC), rely on the Hippo and p53 signalling pathways. However, the upstream regulatory mechanisms of these pathways remain complex and poorly understood. METHODS: Immunohistochemistry (IHC), western blot and RT-qPCR were used to analyse the expression of RNF146, miR-3133 and key components of Hippo and p53 pathway. CCK-8, colony formation, drug sensitivity assays and murine xenograft models were used to investigate the effect of RNF146 and miR-3133 in GIC. Further exploration of the upstream regulatory mechanism was performed using bioinformatics analysis, dual-luciferase reporter gene, immunoprecipitation assays and bisulfite sequencing PCR (BSP). RESULTS: Clinical samples, in vitro and in vivo experiments demonstrated that RNF146 exerts oncogenic effects in GIC by regulating the Hippo pathway. Bioinformatics analysis identified a novel miRNA, miR-3133, as an upstream regulatory factor of RNF146. fluorescence in situ hybridization and RT-qPCR assays revealed that miR-3133 was less expressed in gastrointestinal tumour tissues and was associated with adverse pathological features. Functional assays and animal models showed that miR-3133 promoted the proliferation and chemotherapy sensitivity of GIC cells. miR-3133 affected YAP1 protein expression by targeting RNF146, AGK and CUL4A, thus activating the Hippo pathway. miR-3133 inhibited p53 protein degradation and extended p53's half-life by targeting USP15, SPIN1. BSP experiments confirmed that miR-3133 promoter methylation is an important reason for its low expression. CONCLUSION: miR-3133 inhibits GIC progression by activating the Hippo and p53 signalling pathways via multi-targets, including RNF146, thereby providing prognostic factors and valuable potential therapeutic targets for GIC.

Can we skip technetium-99 m sestamibi scintigraphy in pediatric primary hyperparathyroidism patients with positive neck ultrasound results?

BACKGROUND: Parathyroidectomy is the only curative treatment for primary hyperparathyroidism (PHPT). Ultrasound (US) and technetium-99 m sestamibi (99mTc-MIBI) scintigraphy are recommended as the first-line localization imaging modalities for PHPT in adults, but the value of preoperative imaging in pediatric patients has not been reported. OBJECTIVE: To evaluate the added value of 99mTc-MIBI scintigraphy in pediatric PHPT patients with positive ultrasound results. MATERIALS AND METHODS: Pediatric patients (≤18 years old) who were diagnosed with PHPT and underwent surgical treatment in Peking Union Medical College Hospital between January 2003 and January 2021 were included in this study. Demographic and clinical characteristics, preoperative localization US, 99mTc-MIBI scintigraphy and pathology results were collected. Preoperative localization results were evaluated by comparison with surgical and pathological findings. RESULTS: There were 32 pediatric PHPT patients with median age of 14.7 ± 2.5 years who all proved to have single-gland disease without ectopic lesions. The median lesion size was 2.85 cm (range 1.0-5.8 cm). All patients underwent US and 99mTc-MIBI scintigraphy. Neck US demonstrated 100% sensitivity. Of 32 patients with a positive US, 99mTc-MIBI scintigraphy was concordant in 30 (93.8%). In 2 patients (6.3%), US reported suspected multigland disease, which was correctly diagnosed by 99mTc-MIBI scintigraphy as single lesions. CONCLUSION: In pediatric PHPT patients, US achieved high sensitivity for preoperative localization. 99mTc-MIBI scintigraphy for pediatric patients with positive US results would not increase the sensitivity. Implementation of 99mTc-MIBI scintigraphy could increase the specificity in pediatric patients with multigland disease suspected by US.

Acute inflammatory reaction during anti-angiogenesis therapy combined with immunotherapy as a possible indicator of the therapeutic effect: Three case reports and literature review.

The posterior line treatment of unresectable advanced or metastatic gastrointestinal (GI) tumors has always been a challenging point. In particular, for patients with microsatellite stable (MSS)/mismatch repair proficient (pMMR) 0GI tumors, the difficulty of treatment is exacerbated due to their insensitivity to immune drugs. Accordingly, finding a new comprehensive therapy to improve the treatment effect is urgent. In this study, we report the treatment histories of three patients with MSS/pMMR GI tumors who achieved satisfactory effects by using a comprehensive treatment regimen of apatinib combined with camrelizumab and TAS-102 after the failure of first- or second-line regimens. The specific contents of the treatment plan were as follows: apatinib (500 mg/d) was administered orally for 10 days, followed by camrelizumab (200 mg, ivgtt, day 1, 14 days/cycle) and TAS-102 (20 mg, oral, days 1-21, 28 days/cycle). Apatinib (500 mg/d) was maintained during treatment. Subsequently, we discuss the possible mechanism of this combination and review the relevant literature, and introduce clinical trials on anti-angiogenesis therapy combined with immunotherapy.

[Epidemiological Analysis of Carbapenem-Resistant Enterobacteriaceae Strains in the Clinical Specimens of a Hospital].

Objective: To analyze the detection rate, in vitro susceptibility to antibiotics, and carbapenemase types of carbapenem-resistant Enterobacteriaceae (CRE) strains in the clinical samples of a hospital and to provide support for the prevention, control and treatment of CRE-related infections. Methods: Clinical specimens were examined according to the operating procedures of bacteriological tests. Species identification and in vitro drug susceptibility testing were performed on the isolated strains. Carbapenemase inhibitor enhancement testing, which combined the use of 3-aminobenzeneboronic acid and ethylenediaminetetraacetic acid, was conducted to identify the types of carbapenemase in the CRE strains. Results: In 2021, 2215 CRE strains were isolated from 157196 clinical samples collected in this hospital, presenting a detection rate of 1.4% (2215/157196). A total of 1134 non-repetitive strains of CRE were isolated from 903 patients. The main sources of samples were respiratory tract (494/1134, 43.6%), secretion (191/1134, 16.8%) and blood (173/1134, 15.3%) samples. The cases with the same CRE strain isolated from the samples of two, three and four sites accounted for 12.5%, 4.9%, and 1.1%, respectively. The most common species was Klebsiella pneumoniae (883/1134, 77.9%), followed by Enterobacter cloacae complex (107/1134, 9.4%) and Escherichia coli (96/1134, 8.5%). The rates of resistance to polymyxin B and tigecycline of different species of CRE strains were not significantly different ( P<0.05). Serine carbapenemase-producing strains, metallo-ß-lactamase-producing strains, and those producing both enzymes accounted for 82.6% (809/979), 17.2% (168/979), and 0.2% (2/979), respectively. Conclusion: CRE strains are frequently isolated from samples collected from the respiratory tract, secretion, and blood. The most common strain is serine carbapenemase-producing K. pneumoniae, which has a high resistance rate to various antimicrobial drugs, and risk factors of its associated infections deserve more attention.

[Application of Rapid Detection Method Based on NG-Test® CARBA 5 in Bloodstream Infections Associated With Carbapenem-Resistant Enterobacterales].

Objective: To compare the consistency and accuracy of a rapid test method and a traditional test method for pathogen identification, antimicrobial susceptibility and carbapenemase type identification of positive blood culture samples. Methods: A total of 51 positive blood culture samples of bloodstream infection (BSI) were collected between March 2022 and May 2022. All samples were found to be "positive for Gram-negative bacilli" according to the blood smear results. The rapid method was adopted to perform rapid antimicrobial susceptibility test (RAST) and analysis of the positive blood culture samples. According to the RAST result interpretation standards, NG-Test® CARBA 5 was used for rapid carbapenemase detection of the imipenem-resistant strains and the results were confirmed by PCR. In addition, mass spectrometry, VITEK 2 Compact drug sensitivity analysis, and carbapenemase type identification were performed with the colonies cultured with positive samples according to the traditional method. Results: In the identification of bacteria, the rapid method and the traditional method had 100% consistency rate in the identification results of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. In the antimicrobial susceptibility test, the consistency rate between the results of the two methods was high and the consistency rate for results for susceptibility to imipenem was 100%. In the identification of carbapenemase type, 18 serinase-producing strains and 3 metal-ß-lactamase-producing strains of Enterobacterales were detected by the traditional method. With the rapid method, 18 Klebsiella pneumoniae carbapenemase (KPC)-producing strains, 2 New Delhi metallo-betalactamase (NDM)-producing strains, and 1 imipenem enzyme (IMP)-producing strain were identified in the blood culture samples by using a testing kit. Compared with the PCR results, the sensitivity and specificity of the rapid test for determining carbapenemase types were 100%. In this study, we investigated a rapid method for bacteria and carbapenemase type identification of positive blood culture specimens and found that the turnaround time (TAT) of the rapid method was reduced by 1.94 days on average in comparison with the TAT of the traditional method. Conclusion: The rapid method established in the study can effectively shorten the TAT for pathogenic microorganism identification and antimicrobial susceptibility test of blood culture samples, and the joint report of colloidal gold carbapenemase type identification results can provide a reference for clinicians to use antibiotics appropriately and accurately manage multi-drug resistant bacterial infections.

Qualitative and quantitative superb vascular imaging in the diagnosis of thyroid nodules ≤10 mm based on the Chinese Thyroid Imaging Reporting and Data System 4 (C-TIRADS 4).

Background: To compare qualitative and quantitative superb microvascular imaging (SMI) and determine the value of SMI in the diagnosis of thyroid nodules (TNs) ≤10 mm based on the Chinese Thyroid Imaging Reporting and Data System 4 (C-TIRADS 4). Methods: From October 2020 to June 2022, 106 patients with 109 C-TIRADS 4 (C-TR4) TNs (81 malignant, 28 benign) at the Peking Union Medical College Hospital were included. Qualitative SMI reflected the vascular pattern of the TNs and quantitative SMI was recorded by the vascular index (VI) of the nodules. Results: The VI was significantly higher in malignant nodules versus benign nodules both in the longitudinal (19.9±11.4 vs. 13.8±10.6, P=0.01) and transverse (20.2±12.1 vs. 11.3±8.7, P=0.001) sections. The area under the curve (AUC) of qualitative and quantitative SMI did not show a statistical difference in the longitudinal {0.657 [95% confidence interval (CI): 0.560-0.745] vs. 0.646 (95% CI: 0.549-0.735), P=0.79} and transverse [0.696 (95% CI: 0.600-0.780) vs. 0.725 (95% CI: 0.632-0.806), P=0.51] sections. Next, we combined qualitative and quantitative SMI to upgrade and downgrade the C-TIRADS classification. If a C-TR4B nodule had VIsum >12.2 or intra-nodular vascularity, the original C-TIRADS was upgraded to C-TR4C. If a C-TR4C or C-TR4B nodule manifested VIsum ≤12.2 and no intra-nodular vascularity, the original C-TIRADS was downgraded to C-TR4A. As a result, 18 C-TR4C nodules were downgraded to C-TR4A and 14 C-TR4B nodules were upgraded to C-TR4C. The new model of SMI + C-TIRADS showed high sensitivity (93.8%) and accuracy (79.8%). Conclusions: There is no statistical difference between qualitative and quantitative SMI in the diagnosis of C-TR4 TNs. The combination of qualitative and quantitative SMI may have the potential to manage diagnosis of C-TR4 nodules.

Expert consensus on multidisciplinary approach to the diagnosis and treatment of primary hyperparathyroidism in pregnancy in China.

Primary hyperparathyroidism in pregnancy is a rare disease that can have detrimental effects on both maternal and fetal/neonatal outcomes. The physiological changes that occur during pregnancy can complicate the diagnosis, imaging examinations, and treatment of this disorder. To enhance our understanding and management of primary hyperparathyroidism in pregnancy, experts from various fields, including endocrinology, obstetrics, surgery, ultrasonography, nuclear medicine, pediatrics, nephrology, and general practice in China, collaborated to develop a consensus addressing the critical aspects of the diagnosis and treatment of primary hyperparathyroidism in pregnancy with a multidisciplinary team approach. This consensus provides valuable guidance for healthcare professionals in managing this condition, ultimately improving outcomes for both mothers and their babies.

Long-term Survival, Quality of Life, and Molecular Features of the Patients With Solid Pseudopapillary Neoplasm of the Pancreas: A Retrospective Study of 454 Cases.

OBJECTIVE: To present comprehensive information on the clinicopathological, molecular, survival characteristics, and quality of life (QOL) after surgery for solid pseudopapillary neoplasm (SPN) of the pancreas in a large cohort after long-term follow-up. BACKGROUND: SPN is a rare tumor with an uncertain malignant potential, and solid information on long-term prognosis and QOL remains limited. METHODS: All hospitalized patients with SPNs who underwent surgery between 2001 and 2021 at the Peking Union Medical College Hospital were retrospectively reviewed. The clinicopathological characteristics of the patients were retrieved. A cross-sectional telephone questionnaire was administered to inquire about the QOL. Molecular analyses were performed using whole-exome sequencing. RESULTS: Exactly 454 patients with SPN were enrolled, of whom 18.5% were males and 81.5% were females. The mean patient age was 31 ± 12 years. In total, 61.3% of the patients had no symptoms. The size of the tumors was 5.38 ± 3.70 cm; 83.4% were solid cystic tumors, and 40.1% had calcifications. The proportions of local resection, distal pancreatectomy with or without splenectomy, and pancreaticoduodenectomy with or without pylorus preservation were 29.7%, 28.9% or 22.9%, and 11% or 6.8%, respectively. Over the years, there has been a significant shift from open to minimally invasive surgery. Among all surgical procedures, pylorus-preserving pancreaticoduodenectomy (PPPD) had the highest incidence of grade 2 to 4 complications (up to 32.3%), compared with 6.7% in distal pancreatectomy ( P < 0.001). Regarding histopathology, tissue invasion, perineural invasion, cancerous microvascular emboli, lymph node metastasis, and distant metastasis were present in 16.5%, 2.2%, 0.7%, 2.0%, and 3.1% of patients, respectively. Sixty patients were lost to follow-up. Sixteen of the 390 patients who underwent resection (4.1%) experienced local recurrence or distant metastasis after surgery. In total, 361 patients responded to the telephone survey. Nearly 80% of patients claimed their QOL was not significantly affected after surgery; however, the remaining 20% complained of lower QOL during 3 to 6 years of follow-up after surgery. No clinicopathological factor could reliably predict clinical recurrence or metastasis after resection. A total of 28 driver genes were detected with mutations in at least 2 tumor samples and the top 3 frequently mutated genes were CTNNB1 , ATRNL1 , and MUC16 . CONCLUSIONS: This study presented the largest cohort of patients with SPN after surgery from a single center and reported the QOL of these patients. SPN is associated with extremely favorable long-term survival, even in patients with metastasis, and most patients have a good QOL after surgery.

Predicting multigland disease in primary hyperparathyroidism using ultrasound and clinical features.

Background: The identification of multigland disease (MGD) in primary hyperparathyroidism (PHPT) patients is essential for minimally invasive surgical decision-making. Objective: To develop a nomogram based on ultrasound (US) findings and clinical factors to predict MGD in PHPT patients. Materials and methods: Patients with PHPT who had surgery between March 2021 and January 2022 were consecutively enrolled to this study. Biochemical and clinicopathological data were recorded. US images were analyzed to extract US features for prediction. Logistic regression analyses were used to identify MGD risk factors. A nomogram was constructed based on these factors and its performance evaluated by area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow tests, and decision curve analysis (DCA). Results: A total of 102 PHPT patients were included; 82 (80.4%) had single-gland disease (SGD) and 20 (19.6%) had MGD. Using multivariate analyses, MGD was positively correlated with age (odds ratio (OR) = 1.033, 95% confidence interval (CI): 0.190-4.047), PTH levels (OR = 1.001, 95% CI: 1.000-1.002), multiple endocrine neoplasia type 1 (MEN1) (OR = 29.730, 95% CI: 3.089-836.785), US size (OR = 1.198, 95% CI: 0.647-2.088), and US texture (cystic-solid) (OR = 5.357, 95% CI: 0.499-62.912). MGD was negatively correlated with gender (OR = 0.985, 95% CI: 0.190-4.047), calcium levels (OR = 0.453, 95% CI: 0.070-2.448), and symptoms (yes) (OR = 0.935, 95% CI: 0.257-13.365). The nomogram showed good discrimination with an AUC = 0.77 (0.68-0.85) and good agreement in predicting MGD in PHPT patients. Also, 65 points was recommended as a cut-off value, with specificity = 0.94 and sensitivity = 0.50. Conclusion: US was useful in evaluating MGD. Combining US and clinical features in a nomogram showed good diagnostic performance for predicting MGD.

Diabetes management in patients undergoing total pancreatectomy: A single center cohort study.

Background: Total pancreatectomy (TP) has been increasingly performed in recent years. However, studies on diabetes management after TP during different postoperative periods are still limited. Objectives: This study aimed to evaluate the glycemic control and insulin therapy of patients undergoing TP during the perioperative and long-term follow-up period. Methods: Ninety-three patients undergoing TP for diffuse pancreatic tumors from a single center in China were included. Based on preoperative glycemic status, patients were divided into three groups: nondiabetic group (NDG, n = 41), short-duration diabetic group (SDG, preoperative diabetes duration ≤12 months, n = 22), and long-duration diabetic group (LDG, preoperative diabetes duration >12 months, n = 30). Perioperative and long-term follow-up data, including the survival rate, glycemic control, and insulin regimens, were evaluated. Comparative analysis with complete insulin-deficient type 1 diabetes mellitus (T1DM) was conducted. Results: During hospitalization after TP, glucose values within the target (4.4-10.0 mmol/L) accounted for 43.3% of the total data, and 45.2% of the patients experienced hypoglycemic events. Patients received continuous intravenous insulin infusion during parenteral nutrition at a daily insulin dose of 1.20 ± 0.47 units/kg/day. In the long-term follow-up period, glycosylated hemoglobin A1c levels of 7.43 ± 0.76% in patients following TP, as well as time in range and coefficient of variation assessed by continuous glucose monitoring, were similar to those in patients with T1DM. However, patients after TP had lower daily insulin dose (0.49 ± 0.19 vs 0.65 ± 0.19 units/kg/day, P < 0.001) and basal insulin percentage (39.4 ± 16.5 vs 43.9 ± 9.9%, P = 0.035) than patients with T1DM, so did those using insulin pump therapy. Whether in the perioperative or long-term follow-up period, daily insulin dose was significantly higher in LDG patients than in NDG and SDG patients. Conclusions: Insulin dose in patients undergoing TP varied according to different postoperative periods. During long-term follow-up, glycemic control and variability following TP were comparable to complete insulin-deficient T1DM but with fewer insulin needs. Preoperative glycemic status should be evaluated as it could guide insulin therapy after TP.

Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T.

In recent decades, immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy are two milestone achievements in clinical immunotherapy. However, both show limited efficacies in most solid neoplasms, which necessitates the exploration of new immunotherapeutic modalities. The failure of CAR-T and immune checkpoint blockade in several solid neoplasms is attributed to multiple factors, including low antigenicity of tumor cells, low infiltration of effector T cells, and diverse mechanisms of immunosuppression in the tumor microenvironment. New adoptive cell therapies have been attempted for solid neoplasms, including TCR-T, CAR-natural killer cells (CAR-NK), and CAR-macrophages (CAR-M). Compared to CAR-T, these new adoptive cell therapies have certain advantages in treating solid neoplasms. In this review, we summarized the 40-year evolution of adoptive cell therapies, then focused on the advances of TCR-T, CAR-NK, and CAR-M in solid neoplasms and discussed their potential clinical applications.