Medical Centers In China Research Articles

Prognostic value of neutrophil-to-lymphocyte ratio and cardiac troponin I in patients with immune checkpoint inhibitors-related myocarditis

Abstract Background Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. Purpose We executed a multicenter study aimed at characterizing ICI-related myocarditis and risk factors influencing its prognosis. Methods The study included patients with ICIs-associated myocarditis at four medical centers in China from January 28, 2019 to June 15, 2023. Logistic regression was performed to explore the risk factors for the development of severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of biomarkers to distinguish severe myocarditis, and the performance and calibration were evaluated using Hosmer-Lemeshow test. Cox regression analysis was employed to investigate the influential risk factors affecting the prognosis of ICI-related myocarditis. Kaplan-Meier survival curve analyses were conducted to assess the differences in survival times among different myocarditis groups. Results 35 ICIs-associated myocarditis patients were identified. 21 patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (P=0.013), higher N-terminal pro-B-type natriuretic peptide levels (P=0.031), higher creatine kinase (CK) levels (P=0.018), higher CK-MB levels (P=0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (P=0.016) compared to non-severe myocarditis patients. Multivariate logistic regression showed that cTnI (adjusted odds ratio: 1.021, 95% confidence interval (CI): 1.002-1.039, P=0.03) and NLR (adjusted odds ratio: 1.890, 95% CI: 1.026-3.483, P=0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.765 (95% CI: 0.601 to 0.929, P=0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, P=0.016). Multivariate COX regression showed that NLR (adjusted hazard ratio: 1.189, 95% CI: 1.028-1.376, P=0.020) and pneumonitis (adjusted hazard ratio: 8.142, 95% CI: 1.191-55.651, P=0.032) were the independent prognostic risk factor associated ICI- related myocarditis. Further Kaplan-Meier survival curve analysis showed that the survival rate among patients without pneumonitis and with low level of NLR significantly outstripped that of patients with pneumonitis (P=0.015) and high level of NLR (P=0.024). Conclusions As independent risk factors for the development of ICI-associated severe myocarditis, cTnI and NLR demonstrated a promising predictive utility for the identification of ICI-associated severe myocarditis. NLR and the presence of pneumonitis were identified as independent risk factors that significantly impacted the prognosis of ICI-related myocarditis.

Monocytes perturbation implicated in the association of stress hyperglycemia with postoperative poor prognosis in non-diabetic patients with Stanford type-A acute aortic dissection

ObjectivesThe study aimed to investigate the interaction of intraoperative stress hyperglycemia with monocyte functions and their impact on major adverse events (MAEs) in acute aortic dissection (AAD) patients who underwent open repair surgery.MethodsA total of 321 adults who underwent open surgery for AAD at two tertiary medical centers in China were enrolled in the study. The primary endpoint was defined as the incidence and characteristics of perioperative stress hyperglycemia. The secondary endpoints included the incidence of postoperative MAEs, postoperative monocyte counts and inflammatory cytokine expression. Multi-logistic, linear regression and receiver operating characteristic (ROC) curve analyses were used to establish relationships between intraoperative time-weighted average glucose (TWAG), day-one postoperative monocyte counts, serum inflammatory cytokines and postoperative outcomes. In addition, in vitro experiments were conducted to evaluate changes in the inflammatory features of monocytes under high glucose conditions.ResultsIntraoperative hyperglycemia, as indicated by a TWAG level over 142 mg/dL, was associated with elevated postoperative monocyte counts and inflammatory cytokines, which correlated with extended intensive care unit (ICU) stays and worsened outcomes. In vitro, high glucose treatment induced mitochondrial impairment in monocytes, increased the release of inflammatory cytokines and the proportion of classical monocytes from AAD patients.ConclusionsIntraoperative stress hyperglycemia, in combination with day-one postoperative monocyte counts, were clinically significant for predicting adverse outcomes in AAD patients undergoing open repair surgery. Elevated glucose concentrations shaped the inflammatory features of monocytes in AAD by impairing mitochondrial functions.Graphical abstractHigh glucose-driven mitochondrial functional impairment mediates a more pronounced monocytic inflammatory state in Stanford type-A AAD.

Tryptophan Metabolites Improve Intestinal Mucosal Barrier via the Aryl Hydrocarbon Receptor-Interleukin-22 Pathway in Murine Dextran Sulfate Sodium-Induced Pouchitis.

Pouchitis is the commonest complication after ileal pouch-anal anastomosis for ulcerative colitis. The protective effect of tryptophan metabolites on the mucosal barrier may be an effective method for treating pouchitis. The role of tryptophan metabolites on pouchitis remained unclear. We aimed to establish a murine model of dextran sulfate sodium-induced pouchitis to examine the roles of tryptophan metabolites in its pathogenesis. This is a study combined clinical patient data and animal research. A total of 22 patients were enrolled: 5 with familial adenomatous polyposis after ileal pouch-anal anastomosis, eight ulcerative colitis patients after ileal pouch-anal anastomosis patients with pouchitis, and 9 ulcerative colitis patients after ileal pouch-anal anastomosis with normal pouch. The demographic data and fecal samples of patients were collected. Male C57BL/6 mice were purchased from a licensed breeder and underwent ileal pouch-anal anastomosis to establish murine model of pouch. The bloods, feces, tissues of mice were collected. This study was performed in an academic medical center in China. The demographic data of patients were observational collected. The mice underwent ileal pouch-anal anastomosis were divided into six groups: control group with chow diet, dextran sulfate sodium, 6-formylindolo[3,2-b] carbazole + dextran sulfate sodium, high tryptophan diet + dextran sulfate sodium, CH-223191 + dextran sulfate sodium, indole-3-carboxaldehyde + dextran sulfate sodium. Animals were sacrificed after dextran sulfate sodium for 7 days. Fecal tryptophan metabolite level and microbiome composition, the severity of pouchitis, intestinal mucosal barrier function, and activation of the aryl hydrocarbon receptor-interleukin 22 pathway were assessed. Patients with pouchitis had lower fecal microbial diversity and indole-3-acetic acid levels. In murine pouchitis model, high-tryptophan diet increased fecal levels of 3-indoleglyoxylic acid, indole-3-aldehyde, and indole. A high-tryptophan diet and intraperitoneal aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b] carbazole injection alleviated pouchitis. Tryptophan metabolites improved pouch mucosal barriers. aryl hydrocarbon receptor inhibitors exacerbated experimental pouchitis and disrupted the mucosal barrier; however, the aryl hydrocarbon receptor ligand indole-3-carboxaldehyde reversed this effect. This study was limited by small human sample size and lacking an Aryl hydrocarbon receptor knockout mouse model. A high-tryptophan diet and aryl hydrocarbon receptor ligand alleviated dextran sulfate sodium-induced pouchitis in murine ileal pouch-anal anastomosis model, which might be through regulating epithelial tight junctions and promoting goblet-cell differentiation, as well as maintaining the integrity and function of the mucosal barrier. This study provides a rationale for the clinical application of Aryl hydrocarbon receptor ligands in the treatment of pouchitis. See Video Abstract.

Anti-GABAB receptor encephalitis: clinical and laboratory characteristics, imaging, treatments and prognosis.

Anti-GABABR encephalitis is a rare disease reported to be often associated with tumors. The current study aims to summarize the clinical characteristics, imaging features, treatments, outcomes and explore the potential prognosis risk factors of patients with anti-GABABR encephalitis. Patients tested positive for anti-GABABR were retrospective studied from a single medical center in China over a period of 3 years. They were followed up for a maximum period of 18 months. Clinical data were summarized and prognostic factors including demographic characteristics, laboratory tests, and neurological functions were compared between survived and deceased patients at 18 months follow-up. Twenty-six patients, 10 females (38.5%) and 16 males (61.5%), diagnosed with anti-GABABR encephalitis were studied. The median age was 58 years. Of the 23 cases with complete clinical data, their main manifestations were epileptic seizures (65%), mental and behavioral abnormalities (52%), and cognitive impairment (48%). 7 (30.4%) cases had tumors: 5 small cell lung cancer (SCLC), 1 rectum adenocarcinoma (moderately differentiated) and 1 esophageal squamous cell carcinoma. MRI showed 5 (22%) cases had T2 FLAIR increased signals in cortex but with different regions affected. One of the two patients scanned for PET-CT showed hypermetabolism in the left temporal lobe region. The disease course ranged from 5 days to 3 years. 2 patients (one had esophageal carcinoma) without immunotherapy and 3 patients (one had SCLC) that did not response to immunotherapy died soon after diagnosis. 18 patients improved after immunotherapy while 3 (all had SCLC) died after relapses. The prevalence of epileptic seizures and malignancies was significantly lower in the survival group than in the deceased group at 18-months follow-up, the same as the admission mRs score. Serum fibrinogen, cerebrospinal fluid immunoglobulin G quotient, and 24-hour intrathecal synthesis rate were significantly lower in the survival groups as well. Cortex T2 FLAIR abnormalities were only observed in a small proportion of anti-GABABR encephalitis patients with heterogeneous MRI phenotypes. High mRS score at admission, epileptic seizures and the presence of a tumor indicated a poor prognosis, while the underlying mechanism of the later two factors should be investigated further.

Temozolomide Therapy in Management of Refractory Pituitary Adenomas: A Case Series of 39 Patients

The management of refractory pituitary adenomas (RPA) presents significant challenges. This study aimed to evaluate the long-term treatment outcomes of patients with RPA managed with temozolomide (TMZ) and to identify potential biomarkers for predicting TMZ treatment response. This retrospective case series included patients with RPA who underwent transsphenoidal surgery (TSS) or craniotomy at a comprehensive medical center in China between January 2014 and December 2021. Thirty-nine patients with RPA (median age 42 years; 23 males (59%)) were treated with TMZ for a median of 9 cycles. The median follow-up was 34.4 months. Complete response (CR) was observed in 2 patients, partial response (PR) in 11 patients, stable disease (SD) in 9, progressive disease (PD) in 11, and death in 6 patients. MGMT (O6-methylguanine DNA methyltransferase) levels were significantly lower in patients with CR, PR, or SD compared to those with PD or mortality, with mean values of 24.2% and 58.1, respectively. MSH6 (MutS homologs 6) levels were significantly higher in patients with CR, PR, or SD compared to those with PD or mortality, with mean values of 64.2% and 36.9%, respectively. Patients who received concomitant TMZ and external beam radiotherapy showed a significant tumor size reduction of 178,837mm3 (p<0.001) compared to those treated with TMZ alone. TMZ demonstrates promising efficacy in eliciting tumor responses in patients with PRA. MGMT and MSH6 have emerged as potential biomarkers for predicting treatment response. Furthermore, radiation with concurrent TMZ may significantly improve outcomes in patients with RPA.

Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy(HAIC) Combined with PD-1 Inhibitors for Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Multicenter Propensity Score Matching Analysis.

To investigate the efficacy and safety of HAIC combined with programmed cell death protein-1 (PD1) inhibitors in MVI-positive advanced hepatocellular carcinoma(HCC). From September 2017 to May 2019, we retrospectively collected the clinical data from three medical centers in China pertaining to patients diagnosed with BCLC C stage HCC with MVI and receiving treatment with a combination of HAIC and PD-1 inhibitors treatment or HAIC alone, and we compared the efficacy of HAIC combined with PD-1 inhibitors and HAIC monotherapy. Propensity score matching(PSM) was utilized to adjust for baseline differences between groups. Survival outcomes and tumor response rate were used to assess survival benefits, while the incidence of adverse events was used to evaluate safety. After screening for eligibility, 489 patients diagnosed with HCC and concomitant MVI were enrolled. Of these, 173 patients received treatment combining HAIC with PD-1 inhibitors, while 316 patients underwent HAIC monotherapy. After PSM adjustment, the combination therapy group demonstrate superior survival outcomes. Median overall survival(OS) and progression free survival(PFS) were 31.8 months and 10.8 months, respectively, significantly higher than those in the monotherapy group (OS: 10.0 months; PFS: 6.1 months; both P<0.0001). Moreover, ORR and DCR remained significantly elevated in the combination therapy group (ORR: 44.3% vs 20.4%, P<0.0001; DCR: 89.8% vs 82.0%, P=0.041). Safety profiles indicated no significant differences in adverse event rates between the two treatment groups, encompassing both overall and grade-specific assessments. Compared to HAIC alone, the combination of HAIC with PD-1 inhibitors represents a more promising and effective approach for patients with HCC complicated by macrovascular invasion.

Efficacy of the da Vinci robot versus thoracoscopic surgery for patients with mediastinal tumors of different body mass index: a multicenter propensity score-matched study

BackgroundThe purpose of the present study was to evaluate the efficacy and safety of da Vinci robot-assisted thoracoscopic surgery (RATS) versus video-assisted thoracoscopic surgery (VATS) for the treatment of patients with mediastinal tumors of different body mass indices (BMI).MethodsA retrospective cohort study was used to collect 260 patients with mediastinal tumors admitted to three medical centers in China from December 2020 to March 2024. These patients underwent mediastinal tumor resection by RATS (n = 125) or VATS (n = 135). Propensity score matching (PSM) analysis was performed for the both groups, and further, the patients were divided into the N-BMI group (18.5 kg/m2 ≤ BMI < 25 kg/m2) and the H-BMI group (BMI ≥ 25 kg/m2) based on their BMI to compare patients’ surgery-related information.ResultsThe RATS group had more advantages than the VATS group in terms of intraoperative blood loss, total postoperative drainage, postoperative drainage time, and postoperative hospital stay. As for hospitalization costs, the VATS group was more advantageous. In the H-BMI group, subgroup analysis showed a statistically significant difference in shorter operative time and lower incidence of postoperative complications in the RATS group.ConclusionRATS has technical and short-term efficacy advantages in comparison with VATS, although it has the drawback of high costs associated with the treatment of mediastinal tumors. In the patients with mediastinal tumors of H-BMI, RATS can achieve better short-term outcomes and safety, especially in the reduction of the incidence of postoperative complications.

Effects of the Zishen Yutai Pill on live births compared with placebo among infertile women with frozen-thawed embryo transfer cycle: A multicentre double-blind randomized controlled trial

BackgroundZishen Yutai Pill exhibited clinical benefit to infertile women undergoing fresh embryo transfer cycles, improving their pregnancy outcomes. However, as the endometrial environment in frozen embryo transfer (FET) is different from fresh cycles, the effects of ZYP on fresh embryo transfer could not be generalized to FET. ObjectiveWe aimed to explore the effects of ZYP on live birth rate in women's FET cycles. MethodsThis multicentre, double-blind, placebo-controlled, randomized study was conducted at 11 reproductive medical centres in China. Women were recruited and randomly assigned to ZYP or placebo intervention (5 g once, 3 times per day) around the time of FET. The live birth rate was set as the primary outcome. Secondary outcomes included implantation rate, biochemical pregnancy rate, clinical pregnancy rate, pregnancy loss rates. Data was analyzed based on the intention-to-treat principle, with per protocol analysis as sensitivity analysis. ResultsBetween December 2017 and April 2019, 934 women were screened, of whom 880 met all eligibility criteria and were allocated to ZYP (n=441) or placebo (n=439). In ITT analysis, the live birth rates were 38.32% (169/441) in ZYP group and 32.57% (143/439) (absolute difference 5.75%, 95%CI [−0.57%, 12.00%], OR 1.29, 95%CI [0.98, 1.70], P=0.08). The intervention of ZYP did not result in significantly differences in all secondary outcomes compared with placebo (all P>0.05). Similar trends were observed in PP analysis. In post hoc analysis, ZYP resulted in higher rates of live birth than placebo among women in specific subgroups, i.e., with miscarriage history (39.23% vs. 26.45%, P=0.01) or advanced maternal age (33.93% vs. 21.85%, P=0.04). ConclusionIn infertile women undergoing FET cycle, intervention with ZYP led to a trend of live birth rate increment compared with placebo, but without statistical significance. However, women with miscarriage history and advanced age could experience possible benefits from ZYP intervention. RegistrationChiCTR-INR-17010809 (http://www.chictr.org.cn).

The evaluation of postoperative exocrine pancreatic insufficiency in patients with benign and low-malignant pancreatic tumor: A multicenter, prospective, observational study

Objectives: We assess the incidence of exocrine pancreatic insufficiency (EPI) at different time points after pancreatic surgery and explore pancreatic enzyme replacement therapy's (PERT) efficacy. Background: EPI is characterized by inadequate pancreatic enzymes, resulting in maldigestion and abdominal symptoms. EPI is a common postoperative complication of pancreatic surgery, yet often overlooked by surgeons. There is no clear answer to when EPI occurs after pancreatic surgery nor the duration of PERT after partial pancreatectomy. Methods: Benign or borderline pancreatic tumor patients undergoing surgeries were recruited between December 2020 and November 2021 from 10 medical centers in China. The EPI Questionnaire (EPI-Q) was performed at discharge, and 3-, 6-, 9-, and 12-month follow-ups to evaluate the occurrence of EPI. Statistical analyses were performed to identify the occurrence of EPI and explore PERT's efficacy. Results: Of the 146 patients, 105 (71.9%) were female, and the median age was 49 (range 16-78 yrs). Symptoms of EPI patients were most pronounced within 3 months post-surgery (15.7%), while most patients recovered after 1 year (96.9%). There was a negative correlation between symptom score and time since surgery. Lack of PERT in the 3-month post-surgery was associated with higher symptom scores in pancreatoduodenectomy (PD) patients, while not in distal pancreatectomy (DP) patients. Conclusions: Generally, the high-occurrence period for postoperative EPI is within 3 months after resection in patients with benign or borderline pancreatic tumors, and most will gradually recuperate with time. PERT can improve symptoms in PD patients, while reduced PERT duration may be considered for DP patients.

Outcomes of thoracic endovascular aortic repair with fenestrated surgeon-modified stent-grafts for type B aortic dissection involving the aortic arch: a multicenter retrospective study.

Thoracic endovascular aortic repair (TEVAR) with fenestrated surgeon-modified stent-grafts (f-SMSGs) is becoming an option for treating type B aortic dissection (TBAD) involving the aortic arch. This study aimed to evaluate the outcomes of this technique. A retrospective multicenter study was conducted, involving consecutive patients from three medical centers in China who underwent TEVAR with f-SMSG for TBAD. A new technique called "Lu's direction-turnover technique" was employed to align the fenestrations with supra-aortic vessels. From March 2016 to January 2020, 117 patients diagnosed with TBAD were deemed eligible for inclusion. The technical success rate was 94% (n=110). The estimated 30-day survival rate was 97.4% [95% confidence interval (CI): 94.5% to 100.0%], with freedom from re-intervention estimated at 95.7% (95% CI: 92.0% to 99.4%). The median follow-up period was 27 months (interquartile range, 19 to 35 months). The estimated survival rate at 27 months was 94.9% (95% CI: 90.8% to 98.9%) and the rate of freedom from re-intervention was 91.5% (95% CI: 86.3% to 96.6%). Cases of retrograde type A aortic dissection, stroke and endoleaks were documented. Five cases of retrograde type A aortic dissection were documented, with three occurring within 30 days and one during the follow-up. Four cases of stroke were recorded, with one occurring within 30 days and three during the follow-up. Furthermore, eleven cases of endoleaks were recorded, with one occurring within 30 days and ten during the follow-up. Clinically acceptable technical success and prognosis were observed in a cohort with TEVAR with f-SMSG for the treatment of TBAD involving the aortic arch, which necessitated revascularization of the supra-aortic vessels. Further comparative studies are required to validate the benefits of this approach.

794. RETROSPECTIVE ANALYSIS OF CLINICAL CHARACTERISTICS AND PROGNOSIS OF SYNCHRONOUS MULTIPLE PRIMARY ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Multiple primary esophageal squamous cell carcinoma (MPESCC) is a rare and complex type of esophageal cancer, categorized into synchronous multiple primary esophageal squamous cell carcinoma (S-MPESCC) and metachronous multiple primary esophageal squamous cell carcinoma (M-MPESCC). Compared to solitary esophageal squamous cell carcinoma (SESCC), multiple primary esophageal squamous cell carcinoma (MPESCC) generally has a poorer prognosis, with significant differences in treatment strategies and survival outcomes. This study aims to explore the clinical characteristics and prognosis of S-MPESCC through a retrospective analysis of a large patient cohort. Methods This study retrospectively analyzed clinical data from 758 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgical resection at two medical centers in China from January 2012 to December 2021. The S-MPESCC group included 68 patients, and the SESCC group included 690 patients. All patients underwent radical esophagectomy with systematic lymph node dissection. Preoperative and postoperative data were collected, including gender, age, family history, tumor staging, and lymph node metastasis. Results There were no significant differences in baseline characteristics, such as gender, age, and family history, between the S-MPESCC and SESCC groups. The lymph node metastasis rate was significantly higher in the S-MPESCC group compared to the SESCC group, especially in the upper mediastinal and abdominal regions (P&amp;lt;0.05). Survival status was monitored through outpatient visits and telephone calls until December 2022. The results showed that the 3-year and 5-year survival rates of the S-MPESCC group were significantly lower than those of the SESCC group (P&amp;lt; 0.05). Patients with a greater depth of primary tumor infiltration had poorer survival outcomes in the S-MPESCC group. Conclusion This study clarified the clinical characteristics and prognosis of S-MPESCC through a retrospective analysis of 758 ESCC patients. S-MPESCC patients had a significantly higher rate of lymph node metastasis and a poorer prognosis compared to SESCC patients. Future efforts should focus on optimizing treatment strategies to improve the prognosis and survival rates of patients with S-MPESCC.

Multiregional dynamic contrast-enhanced MRI-based integrated system for predicting pathological complete response of axillary lymph node to neoadjuvant chemotherapy in breast cancer: multicentre study

The accurate evaluation of axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer holds great value. This study aimed to develop an artificial intelligence system utilising multiregional dynamic contrast-enhanced MRI (DCE-MRI) and clinicopathological characteristics to predict axillary pathological complete response (pCR) after NAC in breast cancer. This study included retrospective and prospective datasets from six medical centres in China between May 2018 and December 2023. A fully automated integrated system based on deep learning (FAIS-DL) was built to perform tumour and ALN segmentation and axillary pCR prediction sequentially. The predictive performance of FAIS-DL was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RNA sequencing analysis were conducted on 45 patients to explore the biological basis of FAIS-DL. 1145 patients (mean age, 50 years±10 [SD]) were evaluated. Among these patients, 506 were in the training and validation sets (axillary pCR rate of 40.3%), 127 in the internal test set (axillary pCR rate of 37.8%), 414 in the pooled external test set (axillary pCR rate of 48.8%), and 98 in the prospective test set (axillary pCR rate of 43.9%). For predicting axillary pCR, FAIS-DL achieved AUCs of 0.95, 0.93, and 0.94 in the internal test set, pooled external test set, and prospective test set, respectively, which were also significantly higher than those of the clinical model and deep learning models based on single-regional DCE-MRI (all P<0.05, DeLong test). In the pooled external and prospective test sets, the FAIS-DL decreased the unnecessary axillary lymph node dissection rate from 47.9% to 6.8%, and increased the benefit rate from 52.2% to 86.5%. RNA sequencing analysis revealed that high FAIS-DL scores were associated with the upregulation of immune-mediated genes and pathways. FAIS-DL has demonstrated satisfactory performance in predicting axillary pCR, which may guide the formulation of personalised treatment regimens for patients with breast cancer in clinical practice. This study was supported by the National Natural Science Foundation of China (82371933), National Natural Science Foundation of Shandong Province of China (ZR2021MH120), Mount Taishan Scholars and Young Experts Program (tsqn202211378), Key Projects of China Medicine Education Association (2022KTM030), China Postdoctoral Science Foundation (314730), and Beijing Postdoctoral Research Foundation (2023-zz-012).

Tumor burden score is superior to primary liver cancer stages in predicting prognosis for patients with combined hepatocellular-cholangiocarcinoma after surgery: A multi-center study

BackgroundCombined hepatocellular-cholangiocarcinoma (cHCC-CCA) is poorly understood, while the predictive value of the staging in which it is included is controversial. MethodsPatients with cHCC-CCA underwent radical hepatectomy in two medical centers in China were enrolled and staged based on optimal cut-off values of tumor burden score (TBS), determined using the X-Tile. The association between TBS and prognosis was evaluated by Cox proportional hazard models and Kaplan-Meier curves with Log-rank test. TBS model and primary liver cancer (PLC) stages were compared by discrimination, consistency, and clinical utility, which were further validated by a 5-folds cross-validation. ResultsA total of 192 patients were stratified into low, medium, and high TBS, comprising 92, 51 and 49 patients, respectively. Prognoses worsened with elevated TBS in both the training and validation cohorts. TBS was not only an independent prognostic indicator in univariate and multivariate cox regression, but also a stable risk factor in subgroup analysis according to baseline variables. TBS exhibited best discrimination within these predictive models, as evidenced by the highest c-index and area under curve values of time-dependent receiver operating curves within 5 years post-surgery. TBS calibration plots revealed favorable consistency between prediction and observation. Decision curve analysis suggested higher net benefits for TBS. A 5-folds cross-validation revealed consistent results. ConclusionsTBS could be applied to stratify cHCC-CCA patients after surgery into groups with statistically different prognoses. Moreover, TBS exhibited optimal prognostic value over all available PLC stages and may inform clinical decisions.

Hypogammaglobulinemia and Infection Events in Patients with Autoimmune Diseases Treated with Rituximab: 10 Years Real-Life Experience.

To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.

Targeted gene sequencing reveals disparate genomic mutations between young and older adults in renal cell carcinoma

BackgroundRenal cell carcinoma (RCC) is a type of cancer that can develop at any point in adulthood, spanning the range of age-related changes that occur in the body. However, the specific molecular mechanisms underlying the connections between age and genetic mutations in RCC have not been extensively investigated.MethodsClinical and genetic data from patients diagnosed with RCC were collected from two prominent medical centers in China as well as the TCGA dataset. The patients were categorized into two groups based on their prognosticated age: young adults (YAs) and older adults (OAs). Univariate and multivariate analysis were employed to evaluate the relationships between age and genetic mutations. Furthermore, a mediation analysis was conducted to assess the association between age and overall survival, with genetic disparities serving as a mediator.ResultsOur analysis revealed significant differences in clinical presentation between YAs and OAs with RCC, including histopathological types, histopathological tumor stage, and sarcomatoid differentiation. YAs were found to have lower mutation burden and significantly mutated genes (SMGs) of RCC. However, we did not observe any significant differences between the two groups in terms of 10 canonical oncogenic signaling pathways-related genes mutation, telomerase-related genes (TRGs) mutation, copy number changes, and genetic mutations associated with clinically actionable targeted drugs. Importantly, we demonstrate superior survival outcomes in YAs, and we confirmed the mediating effect of genetic disparities on these survival outcome differences between YAs and OAs.ConclusionOur findings reveal previously unrecognized associations between age and the molecular underpinnings of RCC. These associations may serve as valuable insights to guide precision diagnostics and treatments for RCC.

Hongjin Xiaojie Capsule, a Chinese patent medicine, for treating moderate to severe cyclical breast pain: A single-blind randomized controlled trial

BackgroundModerate to severe breast pain has major effects on the quality of life for patients. Patent Chinese medicines are widely used in the treatment of breast pain due to their stable dosage form and good efficacy. ObjectiveTo evaluate the beneficial effects and safety of Hongjin Xiaojie Capsule (HJXJC), a Chinese patent medicine, for the treatment of cyclical breast pain. Design, setting, participants and interventionThis is a multicenter, single-blind randomized controlled trial conducted in 3 medical centers in China from 2019 to 2021. Patients with moderate to severe cyclic breast pain were randomly divided into the intervention group (who took HJXJC, four capsules per dose, three times a day for 12 weeks) and the control group (waiting for the treatment) in a 1:1 ratio. Main outcome measuresThe primary outcome was pain duration, and the patients recorded measurements at baseline and at the end of weeks 4, 8, 12 and 16 on a patient log card. ResultsThe full analysis set (FAS) population included 298 participants (intervention group, n = 150; control group, n = 148), while the per-protocol analysis set (PPS) included 274 participants. After 12 weeks, the duration of breast pain was significantly shorter in the intervention group (FAS: mean difference, –6.69; 95% CI, –7.58 to –5.80; P < 0.01, vs control. PPS: mean difference, –7.09; 95% CI, –8.01 to –6.16; P < 0.01, vs control). The Short-form McGill Pain Questionnaire (SF-MPQ) scores were significantly lower in the intervention group (FAS: mean difference, –12.55; 95% CI, –13.90 to –11.21; P < 0.01, vs control. PPS: mean difference, –13.07; 95% CI, –14.48 to –11.66; P < 0.01, vs control). The above indicators continued to be significantly different through week 16. Moreover, in the intervention group, breast lumps shrank after 12 weeks and the size of breast lumps was statistically smaller than that in the control group (P < 0.05), whereas the sizes of breast nodules and uterine fibroid showed no statistically significant difference compared with the control group (P > 0.05). At weeks 8 and 12, the dysmenorrhea scores in the intervention group were lower than those in the control group (P < 0.05). No obvious adverse reactions were observed in any group. ConclusionHJXJC can significantly shorten the duration of breast pain, reduce breast pain, reduce the size of breast lumps, and relieve dysmenorrhea. However, it has no significant effect on the size of breast nodules or uterine fibroid. Trial registrationThis trial has been registered at the ISRCTN Registry. Number: ISRCTN44184398. Please cite this article asZhang Q, Fan YY, Wu XQ, Huo YD, Wang CH, Liang SB, Wang T, Zhong R, Wang X, Lai BY, Pei XH, Liu JP. Hongjin Xiaojie Capsule, a Chinese patent medicine, for treating moderate to severe cyclical breast pain: A single-blind randomized controlled trial. J Integr Med. 2024; 22(5): 552–560.

Phi and phiD predict adverse pathological features after radical prostatectomy for prostate cancer in Chinese population.

Anticipating the postoperative pathological stage and potential for adverse features of prostate cancer (PCa) patients before radical prostatectomy (RP) is crucial for guiding perioperative treatment. A cohort consisting of three sub-cohorts with a total of 709 patients has been enlisted from two major tertiary medical centres in China. The primary assessment parameters for adverse pathological features in this study are the pathological T stage, the AJCC prognostic stage groups and perineural invasion (PNI). Logistic regression analyses were performed to investigate the relationship between prostate specific antigen (PSA), its derivatives (incluing Prostate Health Index, phi and phi density, phiD), and the pathological outcomes after RP. Both phi and phiD showed a significant association with pathologic T stage of pT3 or above (phi, adjusted OR, AOR = 2.82, 95% confidence interval, 95% CI: 1.88-4.23, p < 0.001; phiD, AOR = 2.47, 95% CI: 1.76-3.48, p < 0.001) and PNI (phi, AOR = 2.15, 95% CI: 1.39-3.32, p < 0.001; phiD, AOR = 1.94, 95% CI: 1.38-2.73, p < 0.001). In a subgroup analysis with a total PSA value <10 ng/mL, phi and phiD continued to show a significant correlation with pT3 or above (phi, AOR = 4.70, 95% CI: 1.29-17.12, p = 0.019; phiD, AOR = 3.44, 95% CI: 1.51-7.85, p = 0.003), and phiD also maintained its predictive capability for PNI in this subgroup (AOR = 2.10, 95% CI: 1.17-3.80, p = 0.014). Sensitivity analysis indicated that the findings in the combined cohort are mainly influenced by one of the sub-cohorts, partially attributable to disparities in sample sizes between sub-cohorts. Combined analysis of phi(D) and multiparametric MRI (mpMRI) data yielded similar results. Preoperative measurement of serum phi and phiD is valuable for predicting the occurrence of adverse pathological features in Chinese PCa patients after RP.

GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms: A Chinese multicenter study of 12-year experience.

There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs). To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort. Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed. A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods. The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage.

Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer (RATICAL): a nationwide multicenter retrospective study.

Anaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). This study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

Tip bendable suction ureteral access sheath versus traditional sheath in retrograde intrarenal stone surgery: an international multicentre, randomized, parallel group, superiority study

Retrograde intrarenal surgery (RIRS) is the main treatments for upper urinary tract stones. The Ureteral Access Sheath (UAS) serves as a supplementary tool, facilitating direct kidney access during RIRS. High quality of evidence comparing tip bendable suction ureteral access sheath (S-UAS) with traditional UAS in RIRS for the treatment of renal and ureteral stones is lacking. The purpose of the study is to compare the efficacy and safety of S-UAS with traditional UAS in RIRS for the treatment of renal or ureteral stones ≤30mm. An international, multicenter, and superiority randomized controlled trial included 320 intention-to-treat patients across 8 medical centers in China, the Philippines, Malaysia and Turkey from August 2023 to February 2024. The inclusion criteria were patients ≥18 years old with renal or ureteral stones ≤30mm. RIRS was performed using either S-UAS or traditional UAS. The primary outcome was the immediately stone-free rate (SFR). Secondary outcomes included SFR 3 months after operation, operating time, hospital stay, auxiliary procedures, complications (using the Clavien-Dindo grading system), and improvement in the Quality of Life (QoL) score. Differences between proportions [risk difference (RD)]/means [mean difference (MD)] and 95% confidence intervals (CI) were presented. This study is registered at ClinicalTrials.gov: NCT05952635. The S-UAS group demonstrated a significantly higher immediately SFR (81.3% versus 49.4%; RD 31.9%; 95% CI 22.5%-41.7%; p=0.004) compared to the traditional UAS group, as determined by the one-side superiority test. Additionally, the S-UAS group exhibited a higher SFR at 3 months post-operation (87.5% versus 70.0%; RD 17.5%; 95% CI 8.7%-26.3%; p<0.001), lower postoperative fever rate (RD-11.9%; 95% CI-18.7% to-4.9%; p<0.001), reduced use of stone baskets (RD-70.6%; 95% CI-77.8% to-63.5%; p<0.001), and better QoL improvement (MD 7.25; 95% CI 2.21-12.29; p=0.005). No statistically significant differences were observed in operation time, hospital stay, or the need for second-stage RIRS. In RIRS for upper urinary tract stones ≤30mm, S-UAS exhibited superior performance compared to traditional UAS, demonstrating higher SFR, reduced postoperative fever rate, and improved QoL outcomes. S-UAS emerges as a prudent and advantageous alternative to traditional UAS for RIRS. National Natural Science Foundation of China and Guangdong Province, and Zhejiang Medicine and Health Program.