Purpose
This study aimed to evaluate the efficacy of computed tomography (CT) guided percutaneous cryoablation (CA) for the management of lung metastases in patients with metastatic colorectal cancer ...(mCRC).
Methods
Retrospective analysis was performed on 38 mCRC patients with lung metastases, who underwent CT-guided percutaneous CA at our center from May 1, 2020 to November 1, 2021. The technical success rate, 1-year local control (LC) rate, recurrence-free survival (RFS) and treatment-related complications were analyzed.
Results
The CA procedure was successfully performed in all patients, with a technical success rate of 100%. The 1-year LC rate was 94.7% (36/38), while 16 patients experienced new distant lung metastases during the follow-up period. The median RFS was 20 months (95% CI: 13.0-27.0). The median RFS of patients with and without extrapulmonary metastasis was 15 and 23 months, respectively. Complications were reported in 18 (47.4%) patients following the CA procedure. Pneumothorax was discovered in 15 (39.5%) patients, and five of these patients (13.2%) required chest tube intubation. Two patients (5.3%) presented with hemoptysis during the CA procedure. One patient developed subcutaneous emphysema as detected in the post-procedure follow-up imaging. All patients tolerated the peri-procedural pain well under local anesthesia, and the mean visual analog scale (VAS) score was 2.8.
Conclusion
Lung CA is a safe and well-tolerated treatment with a satisfactory local control rate for patients with lung metastases derived from mCRC.
Summary Background Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is ...non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18–75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov , number NCT01040780 , and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67–1·05; median progression-free survival 4·6 months 95% CI 3·5–6·3 vs 3·4 months 2·3–3·8; p=0·13). The most common adverse events were rash (81 41% of 200 patients in the icotinib group vs 98 49% of 199 patients in the gefitinib group) and diarrhoea (43 22% vs 58 29%). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 61% vs 140 70%; p=0·046), especially drug-related diarrhoea (37 19% vs 55 28%; p=0·033). Interpretation Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Managing anticoagulation in pregnant women with mechanical heart valves remains challenging. Our aim was to evaluate the effectiveness and safety of 4 regimens in these women. ...Methods Relevant studies published before June 2015 were collected in several databases and analyzed with RevMan version 5.3 and SPSS version 19.0. Four regimens were defined as follows: a regimen of a vitamin K antagonist (VKA) throughout pregnancy; a heparin (H)/VKA regimen using VKAs except for unfractionated heparin (UFH) or low molecular weight heparin (LMWH) during 6-12 weeks of pregnancy; a LMWH regimen of adjusted LMWH doses throughout pregnancy; and a UFH regimen of adjusted UFH doses throughout pregnancy. The low warfarin dose in the VKA regimen was defined as 5 mg/d or less. Results Fifty-one studies comprising 2113 pregnancies in 1538 women were included. The rate of fetal wastage was significantly higher in the high warfarin dose subgroup than in the low dose one. Compared with the H/VKA regimen, the rate of maternal major thromboembolic event in the low-dose VKA regimen group was significantly lower, although the fetal outcomes were similar. Compared with the H/VKA regimen, the rate of fetal wastage in the LMWH regimen group was significantly lower, and the maternal outcomes were similar. The UFH regimen presented the worst maternal and fetal outcomes. Conclusions In the absence of large prospective trials, this meta-analysis showed that the VKA regimen should be best for pregnant women with a low warfarin dose, and the H/VKA regimen might be reasonable for those with a high warfarin dose. The LMWH regimen could be used for those who refuse VKA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary Background Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. ...We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients. Method Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin-embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients. Findings Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease-free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77·3–94·4) for the low-risk group, and 60% (46·3–71·0) for the high-risk group (hazard ratio HR 4·24, 95% CI 2·13–8·47; p<0·0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74·3–91·8) for the low-risk group, and 57% (42·8–68·5) for the high-risk group (HR 3·63, 1·86–7·01; p<0·0001), and in the independent validation set of patients, was 85% (79·6–89·0) for the low-risk group and 54% (46·4–61·1) for the high-risk group (HR 3·70, 2·56–5·35; p<0·0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1·69, 1·17–2·45; p=0·0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer. Conclusion Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease. Funding Natural Science Foundation of China.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Acute kidney injury frequently arises within an acute care hospitalization. Outcomes among acute kidney injury survivors following hospital discharge are poorly documented. ...Methods We conducted a population-based cohort study between 1996 and 2006 of all adult patients in Ontario with acute kidney injury who did not require in-hospital dialysis, and who survived free of dialysis ≥30 days after discharge. Those with acute kidney injury (n = 41,327) were matched 1:1 to patients without acute kidney injury during their index hospitalization. Matching was by age (±1 year), sex, history of chronic kidney disease, receipt of mechanical ventilation during the index hospitalization, and a propensity score for developing acute kidney injury. The primary outcome was subsequent need for chronic dialysis. The secondary outcomes were all-cause mortality and rehospitalization. Results Mean age was 70 years, and median follow-up was 2 years (maximum 10 years). The incidence of chronic dialysis was 1.78 per 100 person-years among those with acute kidney injury and 0.74 per 100 person-years among unaffected controls (adjusted hazard ratio HR; 2.70, 95% confidence interval CI, 2.42-3.00). Rates also were higher for all-cause mortality (15.34 vs 14.51 per-100 person-years; adjusted HR 1.10; 95% CI, 1.07-1.13) and rehospitalization (44.93 vs 37.18 per 100 person-years; adjusted HR 1.21; 95% CI, 1.18-1.24). Conclusion Even when acute dialysis is not required, survivors of acute kidney injury remain at higher risk of receipt of chronic dialysis thereafter. The absolute risk of death was more than 8 times the rate of chronic dialysis.
Summary Background The novel influenza A H7N9 virus emerged recently in mainland China, whereas the influenza A H5N1 virus has infected people in China since 2003. Both infections are thought to be ...mainly zoonotic. We aimed to compare the epidemiological characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China so far. Methods An integrated database was constructed with information about demographic, epidemiological, and clinical variables of laboratory-confirmed cases of H7N9 (130 patients) and H5N1 (43 patients) that were reported to the Chinese Centre for Disease Control and Prevention until May 24, 2013. We described disease occurrence by age, sex, and geography, and estimated key epidemiological variables. We used survival analysis techniques to estimate the following distributions: infection to onset, onset to admission, onset to laboratory confirmation, admission to death, and admission to discharge. Findings The median age of the 130 individuals with confirmed infection with H7N9 was 62 years and of the 43 with H5N1 was 26 years. In urban areas, 74% of cases of both viruses were in men, whereas in rural areas the proportions of the viruses in men were 62% for H7N9 and 33% for H5N1. 75% of patients infected with H7N9 and 71% of those with H5N1 reported recent exposure to poultry. The mean incubation period of H7N9 was 3·1 days and of H5N1 was 3·3 days. On average, 21 contacts were traced for each case of H7N9 in urban areas and 18 in rural areas, compared with 90 and 63 for H5N1. The fatality risk on admission to hospital was 36% (95% CI 26–45) for H7N9 and 70% (56–83%) for H5N1. Interpretation The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection—a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1. However, the difference in susceptibility to serious illness with the two different viruses remains unexplained, since most cases of H7N9 were in older adults whereas most cases of H5N1 were in younger people. A limitation of our study is that we compared laboratory-confirmed cases of H7N9 and H5N1 infection, and some infections might not have been ascertained. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.
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Acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 gene internal tandem duplication (FLT3-ITD) mutations has a poor prognosis. The combination of arsenic trioxide (ATO) and all-trans ...retinoic acid (ATRA) has a synergistic killing effect on leukemia cells with FLT3-ITD mutation. However, the mechanism, especially the changes of gene expression and metabolic activity remain unclear. Here we explore the transcriptome and metabolomics changes of FLT3-ITD AML cells treated with ATO/ATRA.
RNA-seq was used to identify differential expressed genes (DEGs), and ultra-high performance liquid chromatography-quadrupole electrostatic field orbital trap mass spectrometry (UHPLC-QE-MS) nontargeted metabolomics method was used to screen out the differential metabolites in FLT3-ITD mutant cell lines treated with ATRA and ATO. KEGG pathway database was utilized for pathway exploration and Seahorse XF24 was used to detect extracellular acidification rate (ECAR). Metabolic polymerase chain reaction (PCR) array and real-time quantitative PCR (RT-qPCR) were used to detect mRNA levels of key metabolic genes of glycolysis and fatty acid after drug treatment.
A total of 3873 DEGs were identified and enriched in 281 Gene Ontology (GO) terms, among which 210 were related to biological processes, 43 were related to cellular components, and 28 were related to molecular functions. Besides, 1794 and 927 differential metabolites were screened in positive and negative ion mode separately, and 59 different metabolic pathways were involved, including alanine-aspartate-glutamate metabolic pathway, arginine, and proline metabolic pathway, glycerophospholipid metabolic pathways, etc. According to KEGG Pathway analysis of transcriptome combined with metabolome, glycolysis/gluconeogenesis pathway and fatty acid metabolism pathway were significantly founded enriched. ATRA + ATO may inhibit the glycolysis of FLT3-ITD AML cells by inhibiting FLT3 and its downstream AKT/HK2-VDAC1 signaling pathway.
The gene transcription profile and metabolites of FLT3-ITD mutant cells changes significantly after treatment, which might be related to the anti-FLT3-ITD AML effect. The screened DEGs, differential metabolites pathway are helpful in studying the mechanism of anti-leukemia effects and drug targets.
Lymphatic metastasis is a major determinant of the outcome of resected pancreatic cancer. Gemcitabine-based adjuvant chemotherapy can improve the outcome of resected pancreatic cancer. However, the ...efficacy of gemcitabine against pancreatic cancer stratified by nodal involvement is unclear. In this study, patients who had undergone curative resection of pancreatic adenocarcinoma (612 cases) were included. The efficacy of adjuvant gemcitabine-based regimen, stratified by nodal status (negative, positive) or N substage (N0, no nodal involvement; N1, 1-3-node involvement; N2, ≥4-node involvement), was examined. Both the node-negative (hazard ratio HR = 0.62, 95% confidence interval CI, 0.44-0.87, P = .006) and node-positive subgroups (HR = 0.45, 95% CI, 0.33-0.62, P < .001) benefited from gemcitabine-based adjuvant chemotherapy. Patients with N0 (ie, the node-negative subgroup) or N1 (HR = 0.36, 95% CI, 0.25-0.52, P < .001) disease benefited from gemcitabine-based chemotherapy. However, patients with N2 tumors (HR = 0.95, 95% CI, 0.50-1.78, P = .867) had poor response to gemcitabine-based treatment. Therefore, we postulate that resected pancreatic cancer with N2 node involvement is refractory to gemcitabine-based adjuvant chemotherapy. A more intensive adjuvant regimen may be required for N2 subgroup patients.
Abstract Sex differences in the onset and manifestation of cardiovascular diseases are well known, yet the mechanism behind this discrepancy remains obscure. Estrogen and its corresponding receptors ...have been studied for their positive salutary effects in women for decades. Estrogen protects the heart from various forms of stress, including cytotoxic, ischemic, and hypertrophic stimuli. The postulated underlying mechanism is complex, and involves the actions of the hormone on the endothelium and myocardium. Although the effects of estrogen on the coronary endothelium are well-described, delineation of the hormone's action on cardiomyocytes is still evolving. The focus of this article is to review the accumulated literature and latest data on the role of estrogen and its receptors on cardiomyocytes, the contractile cellular units of the myocardium.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Highlights • This study firstly demonstrated the distribution of causative pathogens among different categories of ICUs within a single multi-specialty hospital in developing country. • Patients in ...surgical ICUs were more susceptible to infections than in medical ICUs. • Gram-negative organisms (e.g. Acinetobacter baumannii ) were the major pathogens in eight ICUs. • Infectious organisms were different between NICU and adult ICUs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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