Systematic investigations of COVID-19 in 283 cancer patients

AbstractsO_ST_ABSBackgroundC_ST_ABSCancer patients are considered to be highly susceptible to viral infections, however, the comprehensive features of COVID-19 in these patients remained largely unknown. The present study aimed to assess the clinical characteristics and outcomes of COVID-19 in a large cohort of cancer patients. Design, Setting, and ParticipantsData of consecutive cancer patients admitted to 33 designated hospitals for COVID-19 in Hubei province, China from December 17, 2019 to March 18, 2020 were retrospectively collected. The follow-up cutoff date was April 02, 2020. The clinical course and survival status of the cancer patients with COVID-19 were measured, and the potential risk factors of severe events and death were assessed through univariable and multivariable analyses. ResultsA total of 283 laboratory confirmed COVID-19 patients (50% male; median age, 63.0 years [IQR, 55.0 to 70.0]) with more than 20 cancer types were included. The overall mortality rate was 18% (50/283), and the median hospitalization stay for the survivors was 26 days. Amongst all, 76 (27%) were former cancer patients with curative resections for over five years without recurrence. The current cancer patients exhibited worse outcomes versus former cancer patients (overall survival, HR=2.45, 95%CI 1.10 to 5.44, log-rank p=0.02; mortality rate, 21% vs 9%). Of the 207 current cancer patients, 95 (46%) have received recent anti-tumor treatment, and the highest mortality rate was observed in the patients receiving recent chemotherapy (33%), followed by surgery (26%), other anti-tumor treatments (19%), and no anti-tumor treatment (15%). In addition, a higher mortality rate was observed in patients with lymphohematopoietic malignancies (LHM) (53%, 9/17), and all seven LHM patients with recent chemotherapy died. Multivariable analysis indicated that LHM (p=0.001) was one of the independent factors associating with critical illness or death. ConclusionsThis is the first systematic study comprehensively depicting COVID-19 in a large cancer cohort. Patients with tumors, especially LHM, may have poorer prognosis of COVID-19. Additional cares are warranted and non-emergency anti-tumor treatment should be cautiously used for these patients under the pandemic.

Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial

ObjectivesTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. DesignMulticenter, open-label, randomized controlled trial. Setting16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. Participants150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. InterventionsHCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). Main outcome measuresThe primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention-to-treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. ResultsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70). The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. ConclusionsThe administration of HCQ did not result in a significantly higher negative conversion probability than SOC alone in patients mainly hospitalized with persistent mild to moderate COVID-19. Adverse events were higher in HCQ recipients than in HCQ non-recipients. Trial registrationChiCTR2000029868 What is already known on this topic-- The pandemic of coronavirus disease 2019 (COVID-19) imposes substantial burdens on individuals, communities, health-care facilities, markets, governments, etc. globally. -- There is no specific treatment approved for COVID-19 or vaccine to prevent infection with the novel coronavirus. -- During the urgent pandemic, media headlines the utility of drugs without solid evidence but buries the side-effects of these drugs. What this study adds-- In this randomized clinical trial of patients mainly with persistent mild to moderate COVID-19, exposure to hydroxychloroquine led to a similar probability of virus elimination comparing to the current standard-of-care. -- Adverse events, mostly gastrointestinal related, were significantly increased in patients who received hydroxychloroquine. -- Overall, the results from our trial do not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19. Print abstractO_ST_ABSStudy questionC_ST_ABSTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. MethodsThis is a multicenter, open-label, randomized controlled trial conducted in 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. A total of 150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. Among them, 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). The primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention to treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. Study answer and limitationsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70) with two serious adverse events. The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. What this study addsOur trial does not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19 due to limited effects on virus eliminating and significantly increased adverse events. Funding, competing interests, data sharingThis work was supported by the Emergent Projects of National Science and Technology (2020YFC0844500), National Natural Science Foundation of China (81970020, 81770025), National Key Research and Development Program of China (2016YFC0901104), Shanghai Municipal Key Clinical Specialty (shslczdzk02202, shslczdzk01103), National Innovative Research Team of High-level Local Universities in Shanghai, Shanghai Key Discipline for Respiratory Diseases (2017ZZ02014), National Major Scientific and Technological Special Project for Significant New Drugs Development (2017ZX09304007), Key Projects in the National Science and Technology Pillar Program during the Thirteenth Five-year Plan Period (2018ZX09206005-004, 2017ZX10202202-005-004, 2017ZX10203201-008). All authors declared no competing interests. Anonymized datasets can be made available on reasonable request after approval from the trial management committee. Study registrationChiCTR2000029868

The clinical significance of PYCR1 expression in renal cell carcinoma.

Pyrroline-5-carboxylate reductase 1 (PYCR1) is an enzyme involved in cell metabolism and is upregulated in cancer. However, the correlations of PYCR1 expression with the clinicopathological features and prognosis of renal cell carcinoma (RCC) remain unclear. The purpose of this study was to identify the expression of PYCR1 and its clinical relevance in RCC patients.PYCR1 mRNA expression differences between RCC and the adjacent normal renal tissues were assessed using the Cancer Genome Atlas database (TCGA). Subsequently, the expression of PYCR1 mRNA and protein were evaluated by quantitative real-time polymerase chain reaction, Western blot, and immunochemistry using 30 paired frozen samples of RCC and the adjacent normal renal tissues. The protein expression of PYCR1 was evaluated by immunostaining formalin-fixed, paraffin-embedded sections of RCC samples from 96 patients who underwent radical nephrectomy, and its relationship with clinical features were analyzed. Nonpaired t tests were used to statistically analyze the differences between the 2 groups. Cox univariable and multivariable analyses of overall survival (OS) among RCC patients were performed.The expression of PYCR1 mRNA was significantly upregulated in RCC tissues compared to adjacent normal renal tissues in the TCGA database (P < .01). The area under the receiver operating characteristic curve value was 0.748. The expression of PYCR1 mRNA and protein was significantly upregulated in RCC compared with that in paired normal renal tissues (P < .01). Higher PYCR1 levels were associated with metastasis (P < .01). Kaplan-Meier survival curves indicated that higher PYCR1 expression was correlated with poorer OS. Therefore, PYCR1 may act as a novel prognostic marker and therapeutic target in the diagnosis and treatment of RCC.

Clinicopathological characteristics of renal solitary fibrous tumor: A single institution experience.

To analyze the clinical characteristics, treatment modalities and outcomes of adult renal solitary fibrous tumors (SFT) treated at a single institution. Demographic, diagnostic, surgical, and pathological findings of patients who had undergone radical nephrectomy (RN) due to renal SFT were collected from the database of a single institution and were retrospectively reviewed. Ten patients (6 men and 4 women) were diagnosed with renal SFT in our institution between January 1, 2000 and December 31, 2016. The mean age was 50.9 ±â€Š8.2 years (range, 38-63 years). Of the 10 patients, 6 were asymptomatic, 2 presented with flank pain, 1 presented with abdominal discomfort, and 1 presented with haematuria. Computed tomography scans were obtained for all patients. Open RN was performed on 6 patients, and laparoscopic RN was performed on 4 patients. The mean tumor size was 10.23 ±â€Š4 cm (range, 5.3-19 cm). Pathological diagnosis revealed that the tumors in 8 patients were benign, while those in the other 2 patients were malignant renal SFT. No recurrence occurred during a mean follow-up period of 47.3 ±â€Š21.5 months (range, 16-85 months). Renal SFT is extremely rare, and its diagnosis may be challenging because of a lack of typical imaging manifestations. RN is a safe treatment modality for benign or low-grade malignant renal SFT, ensuring favorable outcomes.

Expression and clinical significance of long-chain non-coding RNA BCYRN1 in serum of patients with non-small cell lung cancer / 中国医师杂志

Objective To investigate the expression and clinical significance of long-chain noncoding RNA brain cytoplasmic RNA 1 (BCYRN1) in serum of patients with non-small cell lung cancer.Methods 74 patients with non-small cell lung cancer (NSCLC) diagnosed and treated in our hospital were selected as the experimental group,and 50 healthy subjects were selected as the control group.The expression of BCYRN1 in serum of NSCLC and control group was detected by real-time quantitative polymerase chain reaction (qRT-PCR).The patients' clinical pathology data were collected and followed up.To analyze the relationship between the expression of serum BCYRN1 and clinicopathological parameters of NSCLC patients,and the relationship between BCYRN1 expression in the diagnosis and prediction of NSCLC prognosis.Results The relative expression of BCYRN1 in serum of NSCLC patients was 2.84 ± 0.95,which was significantly higher than that of healthy controls (1.16 ± 0.50) (P ＜ 0.05).The level of serum BCYRN1 in patients with NSCLC with tumor size ＞ 3 cm was significantly higher than that in patients with tumor size ≤3 cm (P ＜ 0.05).The level of BCYRN1 in patients with tumor node metastasis (TNM) Ⅲ +Ⅳ was significantly higher than that in patients with stage Ⅰ + Ⅱ (P ＜ 0.05).Patients with low differentiation and positive lymph node metastasis had higher serum BCYRN1 than those with moderate to high grade and lymph node metastasis (P ＜ 0.05).The receiver operating characteristic (ROC) curve analysis showed that the area under the curve was 0.847 (95％ CI:0.772-0.922,P =0.000),and the sensitivity and specificity were 68.9％ and 88.0％,respectively.The median progression free survival (PFS) (15 vs 21 months) and overall survival (OS) (19 vs 28 months) of patients with high and low expression of BCYRN1 were statistically significant (P ＜ 0.05).High expression of BCYRN1 was an independent risk factor for overall survival in patients with NSCLC.Conclusions BCYRN1 is highly expressed in the serum of NSCLC patients,and high expression of BCYRN1 is closely related to the poor prognosis of patients with NSCLC.It can be used as a novel biomarker and diagnostic target for NSCLC.

Expression and clinical significance of long-chain non-coding RNA BCYRN1 in serum of patients with non-small cell lung cancer / 中国医师杂志

Objective@#To investigate the expression and clinical significance of long-chain non-coding RNA brain cytoplasmic RNA 1 (BCYRN1) in serum of patients with non-small cell lung cancer.@*Methods@#74 patients with non-small cell lung cancer (NSCLC) diagnosed and treated in our hospital were selected as the experimental group, and 50 healthy subjects were selected as the control group. The expression of BCYRN1 in serum of NSCLC and control group was detected by real-time quantitative polymerase chain reaction (qRT-PCR). The patients′ clinical pathology data were collected and followed up. To analyze the relationship between the expression of serum BCYRN1 and clinicopathological parameters of NSCLC patients, and the relationship between BCYRN1 expression in the diagnosis and prediction of NSCLC prognosis.@*Results@#The relative expression of BCYRN1 in serum of NSCLC patients was 2.84±0.95, which was significantly higher than that of healthy controls (1.16±0.50) (P<0.05). The level of serum BCYRN1 in patients with NSCLC with tumor size >3 cm was significantly higher than that in patients with tumor size ≤3 cm (P<0.05). The level of BCYRN1 in patients with tumor node metastasis (TNM) Ⅲ+ Ⅳ was significantly higher than that in patients with stage Ⅰ+ Ⅱ (P<0.05). Patients with low differentiation and positive lymph node metastasis had higher serum BCYRN1 than those with moderate to high grade and lymph node metastasis (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve was 0.847 (95% CI: 0.772-0.922, P=0.000), and the sensitivity and specificity were 68.9% and 88.0%, respectively. The median progression free survival (PFS) (15 vs 21 months) and overall survival (OS) (19 vs 28 months) of patients with high and low expression of BCYRN1 were statistically significant (P<0.05). High expression of BCYRN1 was an independent risk factor for overall survival in patients with NSCLC.@*Conclusions@#BCYRN1 is highly expressed in the serum of NSCLC patients, and high expression of BCYRN1 is closely related to the poor prognosis of patients with NSCLC. It can be used as a novel biomarker and diagnostic target for NSCLC.

Effect of dichloroacetate on colony-forming, invasion and migration of the T24 bladder cancer cells line and its mechanism / 实用医学杂志

Objective To study the effects of dichloroacetate (DCA) on cell colony-forming,cell invasion and cell migration of the bladder cancer cells and to study the underlying mechanism.Methods The bldder cancer cells T24 were randomly divided into two groups:the observation group and the control group.Cells in the observation groups were treated with 5 mmol/L,10 mmol/L and 20 mmol/L dichloroacetate,and the control group was treated with the same amount of dimethyl sulfoxide.Colony formation assays were detected with Giemsa staining.Cell wound scratch assay and Transwell assay were applied to evaluate the ability of the T24 cell invasion and migration.Realtime PCR and Western blot were applied to detect the expression of the epithelial-mesenchymal transition (EMT)-related marker,including E-cadherin,N-cadherin,vimentin,Snail and Slug.Results Compared with the control group,the colony formation assays of T24 cells constantly decreased along with the increased doses in the observation group(P ＜ 0.01).The cell wound scratch assay showed that the scratch width of the observation groups were significantly higher along with the increased doses and prolonged time than that in the control group (P ＜ 0.01).The transwell assay showed that the invasion ability of the observation groups were significantly discreased along with the increased doses than that in the the control group (P ＜ 0.01).The expression levels of E-cadherin mRNA and protein in combination the control group were higher than those in the the observation groups (P ＜ 0.05).However,the expression levels of N-cadherin,vimentin,Snail and Slug mRNAs and proteins in combination the control group were lower than those in the the observation groups (P ＜ 0.05).Conclusion Dichloroacetate can inhibit the colony-forming,invasion and migration of bladder cancer T24 cells,and its mechanism may inhibit the expression of epithelial mesenchymal transition in T24 cells by down-regulating the expression of nuclear transcription factor Snail and Slug.

Clinical significance of peripheral blood metastasis and its relationship with BRMS1 / 中华内分泌外科杂志

Objective To investigate the clinical significance of peripheral blood metastasis in breast cancer and its relationship with the metastasis suppressor gene BRMS1.Methods Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of micrometastatic marker hMAM-RNA in the peripheral blood of 149 cases of invasive breast carcinoma.Immunohistochemical method was used to detect the expression of BRMS1 protein in breast cancer tissues after surgery.The recurrence was followed up.SPSS19.0 statistics software was used to analyze the data.Results Among the 149 cases of invasive breast carcinoma patients with preoperative peripheral blood,expression of hMAM-RNA was found in 71 cases,and the micrometastasis rate was 47.65％.Peripheral blood micrometastasis rate in breast cancer was closely related to tumor TMN stage,lymph node metastasis and postoperative recurrence (P＜0.05);while it had nothing to do with patients' age,tumor size,pathological types or tumor tissue typing (P＞0.05).The expression of BRMS1 in postoperative breast cancer tissue was detected in 56 cases,and the positive rate was 37.58％.For BRMS1 positive cases,16 cases had peripheral blood micrometastasis (the positive rate was 28.57％);For BRMS1 negative cases,55 cases had peripheral blood micrometastasis (the positive rate was 51.93％).The difference had statistical significance and the two showed a significant negative correlation(r=-0.296,P＜0.01).With the gradual increase of positive staining intensity of BRMS1 protein,the micrometastasis rate of peripheral blood of breast cancer showed a significant decrease (P＜0.05).At the same time,among patients with positive peripheral blood micrometastasis,the recurrence rate of patients with positive BRMS1 (12.5％) was significantly lower than that of patients with negative BRMS1 (43.64％),and the difference was statistically significant(P＜0.05).Conclusions BRMS 1 expression and breast cancer micrometastasis in peripheral blood is closely related.BRMS1 can also be used as an important molecular marker for determining micrometastasis in peripheral blood of breast cancer.Routine detection of BRMS1 expression in breast cancer tissue is helpful for clinical understanding of breast cancer patients,peripheral blood micrometastasis and postoperative recurrence,thus guiding clinical individualized treatment and prognosis.

Evaluation of left ventricular diastolic and systolic function of dogs on different status of acute myocardial ischemia with velocity vector imaging / 中国医学影像技术

Objective To evaluate left ventricular diastolic and systolic function of the dogs during different status of acute myocardial ischemia with velocity vector imaging (VVI). Methods Six healthy mongrel dogs were enrolled. Home-made artery constrictor was placed in the proximal coronary artery after opening the chest of dogs to produced different grades of coronary artery stenosis. Mean of peak diastolic velocity (Em), peak strain rate of diastole (Esr), mean of peak systolic velocity (Sm), peak strain rate of systole (Ssr), ejection fraction (EF) and left ventricular pressure were measured. Results There was good linear correlation between Em and Esr by VVI and left ventricular end diastolic pressure (LVEDP) (r=-0.834, P＜0.001 and r=-0.703, P＜0.001, respectively). Em and LVEDP had better correlation than that between Esr and LVEDP (P=0.032). Sm, Ssr or EF had significant correlation with +dp/dt_(max) (r=0.883, P＜0.001, r=0.772, P＜0.001 and r=0.647, P＜0.001, respectively). Significant difference was observed for correlation coefficient between Em and Esr and EF (P＜0.001). Conclusion Em and Sm are sensitive echocardiography indexes to evaluate left ventricular diastolic and systolic function, and are better than EF, Esr and Ssr.

The theraputic effect of Chinese Medicine Jiaweidingchuan Soup on inflamation in patients with asthma / 中国实用内科杂志

Objective To determine the efficacy and safety of Chinese Medicine Jiaweidingchuan Soup in the treatment of asthma.MethodsPatients(n =32)with mild-to-moderate asthma were treated with Chinese Medicine Jiaweidingchuan Soup for 4 weeks.We measured the FVC、FEV1、PEF、IL-6 and IFN-? level.ResultsAfter treatment,the FVC、FEV1 and PEF values and the expression of IFN-? in patient with asthma increased significantly(P

Comparative Study on the Mechanism of Formation of Pulse Manifestations in Patients of Coronary Heart Disease and Hematopathy / 中医杂志

Most of the CHD patients reveal string pulse, mainly due to damage of heart function, lowering of arterial compliance and increase of total peripheral resistance. The common pulse in patients of blood diseases reveal frequent, tiny, string and slippery characteristic, mostly due to the increase of compensatory pumping action of the heart, shortening of ejection time of the left heart, with better vessel compliance and hemorheology, low total peripheral resistance.