Background Recurrent hepatocellular carcinoma (RHCC) after curative resection is a major challenge for hepatic surgeons. A better understanding of the clonal origin of RHCC will help clinicians ...design personalized therapy and assess postoperative outcomes. The current study was performed to determine the clonal origin of RHCC and its clinical significance. Study Design Fifteen high-frequency of loss of heterozygosity of DNA microsatellites were determined on 100 tumor nodules in 60 matched pairs of RHCC from 40 patients who underwent liver re-resections. The relationships among the origin of clonal patterns of RHCC and the surgicopathologic features and clinical outcomes were analyzed. Results Of 60 pairs of RHCC, there were 2 clonal patterns with 6 subclonal types. Pattern I was multicentric occurrence (MO type) in 14 pairs (23.3%) and pattern II was intrahepatic metastasis (IM type) in 46 pairs (76.7%). The clinicopathologic features, including recurrence time, tumor size, vascular invasion, histological grading, and associated chronic liver diseases in patients with the MO type of RHCC were significantly different from those with the IM type of RHCC (p < 0.05 to 0.001). Compared with patients in the IM group, patients in the MO group had significantly better overall survival (130.8 ± 8.5 months vs 80.8 ± 8.5 months; p < 0.05) and recurrence-free survival (33.8 ± 4.5 months vs 14.2 ± 2.5 months; p < 0.001). Conclusions The MO-type RHCC was closely associated with better postoperative outcomes when compared with the IM-type RHCC. Generally, we recommend liver re-resection for MO-type RHCC, and interventional therapy for IM-type RHCC. Microdissection-based microsatellite loss of heterozygosity protocol has advantages in assessing the clonal origin, modes of personalized treatment, and clinical outcomes of RHCC.
Type 2 diabetes is a major threat to human health in the 21st century. More than half a billion people may suffer from this pandemic disease in 2030, leading to a huge burden of cardiovascular ...complications. Recently, 2 novel antidiabetic agents, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular complications in a number of randomized control trials. To integrate new information and to achieve a streamlined process for better patient care, a working group was appointed by the Taiwan Society of Cardiology to formulate a stepwise consensus pathway for these therapies to reduce cardiovascular events in patients with type 2 diabetes. This consensus pathway is complementary to clinical guidelines, acting as a reference to improve patient care.
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•SGLT2 inhibitors and GLP-1 RAs decreased cardiovascular endpoints in a majority of clinical trials.•SGLT2 inhibitors are more effective in preventing and reducing renal endpoints and heart failure, while GLP-1 RAs are more effective in preventing and reducing stroke.We have developed a stepwise algorithm, using 5 clinical parameters, to prioritize specific medication in different clinical settings, including patients with ASCVD or risk factors alone.
Abstract Background Relapsed or refractory Hodgkin's lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of ...CD30-targeting CAR T cells in patients with progressive relapsed or refractory Hodgkin's lymphoma, in which CD30 expression is mostly positive. Methods This open-label, phase 1 study took place at the Chinese PLA General Hospital. Eligible patients (aged 16–80 years) had relapsed or refractory Hodgkin's lymphoma. All patients received a conditioning chemotherapy regimen at the discretion of physician, followed by the infusion of CD30-directed CAR T cells. Using escalating doses to avoid severe toxicity associated with infusion, patients received a starting dose of 3·2 × 105 CAR T cells per kg and then infused by 5-fold increments continuously for 3–5 days. After the dose-escalation infusion, no patients experienced greater than grade 3 toxicity events. We periodically monitored the expression level of CAR transgenes in peripheral blood and biopsied tumour tissues according to assigned protocol by quantitative PCR. Two-way analysis of variance (ANOVA) was used to determine the significance of the differences between means in all experiments. This trial was approved by the Institutional Review Board at the Chinese PLA General Hospital and is registered with ClinicalTrials.gov , number NCT02259556 . All patients gave written informed consent before enrolment. Findings Between Dec 1, 2014, and Mar 1, 2015, 11 patients were enrolled. All of whom had a heavy pretreatment history (15 previous treatments, range 6–24) or multiple tumour lesions (3·3 lymph node regions involved, range 0-7; involvement of one or more extralymphatic organs), or both. The patients received a mean of 1·5×107 CAR-positive T cell per kg (SD 0·25, range 1·2–2·1) in total during infusion. Nine (82%) patients responded to the treatment: one (9%) patient maintained continuous complete remission, five (46%) patients achieved partial response, and three (27%) patients achieved stable disease. All patients experienced tolerable infusion-related febrile syndrome. One (9%) patient had 5 days of self-limiting arthralgia, myalgia, and dual knee swelling 2 weeks after cell infusion. The copy number of CAR transgene in peripheral blood peaked 3–17 days after infusion, which was accompanied by a two-times higher increase in the number of lymphocytes. Analysis of biopsied tissues revealed a highly efficient trafficking of CAR T cells into the targeted sites. Interpretation CD30-directed CAR T-cell therapy was safe, feasible, and efficient in patients with relapsed or refractory Hodgkin's lymphoma and guaranteed a large-scale patients recruitment. Funding Science and Technology Planning Project of Beijing City (No. Z151100003915076) and National Natural Science Foundation of China (Nos. 31270820, 81230061, 81121004, and 81402566).
Objective Patients with inflammatory rheumatic diseases have an increased risk of developing coronary atherosclerosis. However, outcomes of surgical revascularization in these patients have been ...rarely studied. We aimed to determine whether, or which, inflammatory rheumatic diseases may pose effects on mortality and adverse cardiac outcomes after coronary artery bypass grafting. Methods By using the National Health Insurance Research Database of Taiwan, we identified 40,639 adult patients who underwent first-time coronary artery bypass grafting between 2000 and 2010. Among these patients, 101 had rheumatoid arthritis, 56 had systemic lupus erythematosus, and 73 had ankylosing spondylitis. The odds ratios (ORs) of operative mortality and hazard ratios (HRs) of overall mortality and adverse cardiac outcomes after coronary artery bypass grafting (ie, myocardial infarction and repeat revascularization) in relation to rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis were estimated. Results With adjustment for potential confounders including patient characteristics, hospital levels, and combined surgery, systemic lupus erythematosus was an independent predictor for operative mortality (adjusted OR, 2.63; 95% confidence interval CI, 1.04-6.65; P = .04) and ankylosing spondylitis was marginally associated with operative mortality (adjusted OR, 2.41; 95% CI, 0.99-5.88; P = .054). Systemic lupus erythematosus was a significantly independent predictor for overall mortality during the follow-up period (adjusted HR, 2.23; 95% CI, 1.51-3.31; P < .0001) and might increase the risk of repeat revascularization (adjusted HR, 1.89; 95% CI, 0.97-3.68; P = .06). Neither rheumatoid arthritis nor ankylosing spondylitis was significantly associated with overall mortality and adverse cardiac outcomes. Conclusions Our study may help surgeons and physicians recognize the potential risks inherent to systemic lupus erythematosus and ankylosing spondylitis when conducting coronary artery bypass grafting and providing follow-up care.
A 16-year-old boy presented with growth retardation and iron deficiency anemia. The disease was identified incidentally in the pararenal retroperitoneum after computed tomography and magnetic ...resonance imaging scans. A retroperitoneal lesion was removed in its entirety and was histologically confirmed to be a symptom of Castleman's disease of the unicentric plasma cell type. The unicentric plasma cell type appears so rarely in the retroperitoneum that a similar case has been reported only once. The patient was discharged on day 9 after surgery without significant complications and grew 18 cm within a year.
Background: Cancer-related pain is one of the primary symptoms of patients with hepatocellular carcinoma (HCC). Previous studies have shown that transcutaneous electrical acupoint stimulation (TEAS) ...is effective in treating patients with acute or chronic pain. In China, it is indispensable to evaluate the efficacy of TEAS in combination with opioids for the treatment of moderate to severe HCC-related pain. Methods/Design: This is a single-center clinical, prospective randomized controlled clinical trial protocol. 104 patients will be randomly divided into the observation group and the control group in a ratio of 1:1. In addition to routine cancer pain medication, the two groups of patients will receive TEAS treatment twice a day for one week. Acupoints will include bilateral Hegu(LI4), Neiguan (PC6), Zusanli(ST36), Taichong(LR3), Ganshu(BL18), Geshu(BL17), Qimen(LR14), and Zhangmen(LR13). The treatment time is from 9:00 a.m. to 11:00 p.m. and from 4:00 p.m. to 6:00 p.m. The primary outcome measures are the Numerical Rating Scale (NRS) and the secondary outcome measures include the Brief Pain Inventory(BPI), dosage and administration duration of opioid drugs, frequency of nausea, vomiting and defecation, Karnofsky Performance Status Scale (KPS), Quality of life scale (QOL), Brief Fatigue Inventory (BFI). The outcome measures will be evaluated at baseline, during treatment and 1 week after treatment. Discussion: Results of this trial are expected to clarify the value of TEAS stimulation performed on specific points in the management of moderate to severe pain in HCC. Trial registration: Chinese clinical trial registry, ChiCTR2100044615 ( Keywords: protocol, hepatocellular carcinoma, TEAS, pain
The adsorption of two basic dyes (Basic Green 5 (BG5) and Basic Violet 10 (BV10)) onto titanate nanotubes (TNT) that were prepared via a hydrothermal method with different synthesis temperatures was ...studied to examine the potential of TNT for the removal of basic dyes from aqueous solution. Effects of synthesis temperature on the microstructures of TNT were characterized with transmission electron microscopy (TEM), X-ray diffraction (XRD), and nitrogen adsorption–desorption isotherms. For synthesis temperature greater than 160
°C, the microstructure of titanate might transform from nanotube into nanorod accompanying with the sharp decrease in the titanate interlayer spacing, BET surface area, and pore volume. Effects of the pore structure variation on the basic dyes adsorption of TNT were discussed. Moreover, the adsorption mechanisms of basic dyes from aqueous solution onto TNT were examined with the aid of model analyses of the adsorption equilibrium and kinetic data of BG5 and BV10. The regeneration of TNT was also briefly discussed.
Summary Background Prophylactic treatment of individuals with latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control in some settings. In China, the prevalence ...of latent tuberculosis infection, and preventive interventions against this disease, have not been systematically studied. We aimed to assess the prevalence of latent tuberculosis and its associated risk factors in rural populations in China. Methods Between July 1, and Sept 30, 2013, we undertook a baseline survey of a population-based, multicentre, prospective cohort study of registered residents (≥5 years old) at four study sites in rural China. Eligible participants were identified by door-to-door survey with a household sampling design. We screened participants for active tuberculosis and history of tuberculosis then used a tuberculin skin test and an interferon-γ release assay (QuantiFERON QFT) to test for latent infection. We used odds ratios (ORs) and 95% CIs to assess variables associated with positivity of QFT and tuberculin skin tests. Findings 21 022 (90%) of 23 483 eligible participants completed a baseline survey. Age-standardised and sex-standardised rates of skin-test positivity (≥10 mm) ranged from 15% to 42%, and QFT positivity rates ranged from 13% to 20%. Rates of positivity for the tuberculin skin test and the QFT test were low in study participants younger than 20 years and gradually increased with age (p for trend <0·0001). Rates of latent tuberculosis infection were higher for men than women (p<0·0001). Overall agreement between the tuberculin skin test and the QFT test was moderate (81·06%; kappa coefficient 0·485), with skin-test-only positive results associated with the presence of BCG scar, male sex, and ages of 60 years and older, and QFT-only positive results associated with male sex and ages of 60 years and older. Interpretation On the basis of findings showing that the performance of the tuberculin skin test might be affected by various factors including BCG vaccination and age, our results suggest that the prevalence of latent tuberculosis in China might be overestimated by skin tests compared with interferon-γ release assays. Funding The National Science and Technology Major Project of China, the Program for Changjiang Scholars and Innovative Research Team in University of China.
Lung cancer is the leading cause of cancer-related morbidity and mortality in the People’s Republic of China. Targeted therapies for patients with lung cancer, which depend on accurate identification ...of actionable genomic alteration, have improved survival compared with previously available treatments. However, data on the types of molecular testing often used in the People’s Republic of China, and how they have changed over time, are scarce. We explored the overall landscape of molecular testing of lung cancer in mainland People’s Republic of China in the past decade.
We distributed a stratified random sampling survey of molecular testing to 49 hospitals from members of the Molecular Pathology Collaboration Group of Chinese Anti-Cancer Association which was weighted by the numbers of lung cancer cases in seven different geographic regions in mainland People’s Republic of China from 2010 to 2019. The questionnaire contained four parts for all respondents. The questionnaire ascertained the use of approved in vitro diagnostic (IVD) devices published by the Center for Medical Device Evaluation, National Medical Products Administration of the People’s Republic of China.
A total of 226,227 NSCLC specimens were tested from 2010 to 2019 in the selected hospitals. The annual number of initiated molecular tests increased over time (p < 0.0001), with an average annual growth rate of 31.8%. A notable increase in the number of molecular tests occurred during 2014 and 2016, which coincided with the approval of the National Medical Products Administration to IVD devices. For the diagnosis of molecular subtypes, EGFR mutation testing was first conducted in year 2007, followed by ALK translocation testing in 2010 and ROS1 in 2011. For other rare genetic variations in NSCLC, BRAF mutation testing was first launched in 2012, MET exon 14 skipping mutation in 2014, HER2 exon 20 mutations in 2017, and RET translocation in 2015. A markedly uneven distribution was also observed in the geography of leading units with the largest number of leading units located in east People’s Republic of China (34.7%, 17 of 49) and the smallest number located in northwest People’s Republic of China (6.1%, 3 of 49). The growth trends we observed illustrate the progress and increasing capability of molecular testing of lung cancer achieved in mainland People’s Republic of China in the decade from 2010.
In the decade 2010 to 2019, progress and increased capability of molecular testing of lung cancer were achieved in mainland People’s Republic of China. Further efforts should address the clinical application of next-generation sequencing technology, rare genomic aberrations, and the balance between novel genomic testing techniques and the approval of IVD products.
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