Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.

Long-term outcomes of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): a randomized, multicenter, prospective, phase III trial.

BACKGROUND: We aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients. METHODS: We performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival actualization after long-term follow-up was performed in patients analyzed on an intention-to-treat basis. RESULTS: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients (3-year DFS: 91.1% vs. 90.0%, P=0.328; 3-year OS: 94.4% vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148-0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353-0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment CEA levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233-0.921, P=0.029 and OS: (HR=0.476, 95% CI: 0.223-1.017, P=0.049). CONCLUSIONS: Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5 ng/ml), intraoperative chemotherapy could improve long-term survival.

Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial.

OBJECTIVE: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). BACKGROUND DATA: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. METHODS: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. RESULTS: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. CONCLUSIONS: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

Comprehensive profiling of 1015 patients' exomes reveals genomic-clinical associations in colorectal cancer.

The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research.

Effect of Shenmai Injection on Long-Term Prognosis of Patients with Chronic Heart Failure: A Multicenter, Large Sample Capacity, Long-Term Follow-Up Retrospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Shenmai Injection (SMI) on the long-term prognosis of patients with chronic heart failure (CHF).@*METHODS@#The Hospital Information System was used to extract data of CHF patients, and the retrospective cohort study was conducted for analysis. In non-exposed group, standardized Western medicine treatment and Chinese patent medicine or decoction were applied without combination of SMI while in the exposed group, SMI were applied for more than 7 days. Evaluation indicators are followed with New York Heart Association functional classification (NYHA classification), left ventricular ejection fraction (LVEF), N-terminal brain natriuretic peptide precursor (NT-ProBNP), cardiogenic death and heart failure (HF) readmission. Statistical analysis includes Kaplan-Meier analysis and Cox regression which are used to explore the relationship between SMI and outcome events.@*RESULTS@#A total of 1,211 eligible CHF patients were involved and finally 1,047 patients were followed up successfully. After treatment, the cases of NYHA classification decline in the exposed and non-exposed groups accounted for 64.30% and 43.45%, respectively; the improvement values of LVEF were 8.89% and 7.91%, respectively; the improvement values of NT-ProBNP were 909 pg/mL and 735 pg/mL, respectively. After exposure on SMI, the rates of cardiogenic death and HF readmission reduced from 15.43% to 10.18% and 38.93% to 32.37%. According to Kaplan-Meier analysis, the log-rank P value of SMI and cardiogenic death was 0.014, while the counterpart of SMI and HF readmission was 0.025. Cox regression analysis indicated that for cardiogenic death, age, cardiomyopathy, diabetes, and NYHA classification were risk factors while β-blockers, aldosterone receptor antagonists, Chinese patent medicine/decoction and SMI were protective factors. Likewise, for HF readmission, age, cardiomyopathy, and NYHA classification were risk factors while SMI was a protective factor.@*CONCLUSION@#Combination with SMI on the standardized Western medicine treatment can effectively reduce cardiogenic mortality and readmission rate in CHF patients, and thereby improve the long-term prognosis.

Assessment of defecation function after sphincter-saving resection for mid to low rectal cancer: A cross-sectional study.

PURPOSE: Patients with mid-to low-rectal cancer can have various dysfunctions of defecation after sphincter-saving resection. Defecation dysfunction can manifest as incontinence, urgency, or frequent bowel movements, and is called low anterior resection syndrome (LARS). This study aimed to examine LARS score and objective anorectal function indices in Chinese patients receiving sphincter-saving surgery for mid-to low-rectal cancer. METHOD: This was a single-center cross-sectional study of patients undergoing sphincter-saving resection for low- or mid-rectal cancer and had restoration of trans-anal defecation for at least 1 month seen between January 2019 and June 2020. Patients completed a questionnaire regarding clinical characteristics, and Low Anterior Resection Syndrome (LARS) score and high-resolution anorectal manometry (HR-ARM) were used to assess defecation function. Multivariable analysis was used to identify variables significantly associated with defecation dysfunction. RESULTS: 146 patients completed and returned the questionnaires. 25 healthy adults also participated as control group for the anorectal manometry. Approximately 76% of patients developed LARS after surgery, of which 35.6% had major LARS. In these patients, anorectal manometry indices including initial rectal sensory capacity and rectal fecal sensory capacity, were significantly lower than normal. Logistic regression analysis showed that preoperative chemo-radiotherapy and the tumor inferior margins being close to the dentate line, especially 2-5 cm, were independent risk factors for defecation dysfunction after surgery. CONCLUSIONS: Defecation dysfunction is a frequent occurrence after sphincter-saving resection for mid- and low-rectal cancer. Preoperative chemo-radiotherapy and a shorter tumor inferior margins distance to the dentate line are independent factors for defecation dysfunction.

Beneficiaries of radical surgery among clinical complete responders to neoadjuvant chemoradiotherapy in rectal cancer.

This study aimed to identify patients who benefit from radical surgery among those with rectal cancer who achieved clinical complete response (cCR). Patients with locally advanced rectal cancer (LARC; stage II/III) who achieved cCR after neoadjuvant chemoradiotherapy (nCRT) were included (n = 212). Univariate/multivariate Cox analysis was performed to validate predictors for distant metastasis-free survival (DMFS). A decision tree was generated using recursive partitioning analysis (RPA) to categorize patients into different risk stratifications. Total mesorectal excision (TME) was compared with the watch-and-wait (W&W) strategy in each risk group. Two molecular predicators of CEA and CA19-9 were selected to establish the RPA-based risk stratification, categorizing LARC patients into low-risk (n = 139; CA19-9 < 35 U/mL and CEA < 5 ng/mL) and high-risk (n = 73; CA19-9 ≥ 35 U/mL or CEA ≥5 ng/mL) groups. Superior 5-y DMFS was observed in the low-risk group vs. the high-risk group (92.9% vs. 76.2%, P = .002). Low-risk LARC patients who underwent TME had significantly improved 5-y DMFS compared with their counterparts receiving the W&W strategy (95.9% vs. 84.3%; P = .028). No significant survival difference was observed in high-risk patients receiving the 2 treatment modalities (77.9% vs. 94.1%; P = .143). LARC patients with cCR who had both baseline CA19-9 < 35 U/mL and CEA < 5 ng/mL may benefit from radical surgery.

Neoadjuvant chemoradiotherapy in patients with unresectable locally advanced sigmoid colon cancer: clinical feasibility and outcome.

BACKGROUND: Patients with locally advanced sigmoid colon cancer (LASCC) have limited treatment options and a dismal prognosis with poor quality of life. This retrospective study aimed to further evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by surgery as treatment for select patients with unresectable LASCC. METHODS: We studied patients with unresectable LASCC who received NACRT between November 2010 and April 2019. The NACRT regimen consisted of intensity modulated radiotherapy (IMRT) of 50 Gy to the gross tumor and positive lymphoma node and 45 Gy to the clinical target volume. Capecitabine­based chemotherapy was administered every 2 (mFOLFOX6) or 3 weeks (CAPEOX). Surgery was scheduled 6-8 weeks after radiotherapy. RESULTS: Seventy­two patients were enrolled in this study. Patients had a regular follow-up (median, 41.1 months; range, 8.3-116.5 months). Seventy­one patients completed NACRT, and sixty-five completed surgery. Resection with microscopically negative margins (R0 resection) was achieved in 64 patients (88.9%). Pathologic complete response was observed in 15 patients (23.1%), and multivisceral resection was necessary in 38 patients (58.3%). The cumulative probability of 3-year overall survival (OS) and progression-free survival (PFS) were 75.8 and 70.7%, respectively. CONCLUSIONS: For patients with unresectable LASCC, neoadjuvant chemoradiotherapy is feasible, surgery can be performed safely and may result in increased survival and organ preservation rates.

Neoadjuvant chemoradiotherapy for patients with unresectable radically locally advanced colon cancer: a potential improvement to overall survival and decrease to multivisceral resection.

BACKGROUND: The management of unresectable locally advanced colon cancer (LACC) remains controversial, as resection is not feasible. The goal of this study was to evaluate the treatment outcomes and toxicity of neoadjuvant chemoradiotherapy (NACRT) followed with surgery and adjuvant chemotherapy in patients with unresectable radically LACC. METHODS: We included patients who were diagnosed at our institution, 2010-2018. The neoadjuvant regimen consisted of radiotherapy and capecitabine/ 5-fluorouracil-based chemotherapy. RESULTS: One hundred patients were identified. The median follow-up time was 32 months. The R0 resection rate, adjusted nonmultivisceral resection rate and bladder preservation rate were 83.0, 43.0 and 83.3%, respectively. The pCR and clinical-downstaging rates were 18, and 81.0%%, respectively. The 3-year PFS and OS rates for all patients were 68.6 and 82.1%, respectively. Seventeen patients developed grade 3-4 myelosuppression, which was the most common adverse event observed after NACRT. Tumor perforation occurred in 3 patients during NACRT. The incidence of grade 3-4 surgery-related complications was 7.0%. Postoperative anastomotic leakage was observed in 3 patients. CONCLUSIONS: NACRT followed by surgery was feasible and safe for selected patients with LACC, and can be used as a conversion treatment to achieve satisfactory downstaging, long-term survival and quality of life, with acceptable toxicities.

The watch-and-wait strategy versus surgical resection for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy.

BACKGROUND: The watch-and-wait strategy offers a non-invasive therapeutic alternative for rectal cancer patients who have achieved a clinical complete response (cCR) after chemoradiotherapy. This study aimed to investigate the long-term clinical outcomes of this strategy in comparation to surgical resection. METHODS: Stage II/III rectal adenocarcinoma patients who received neoadjuvant chemoradiotherapy and achieved a cCR were selected from the databases of three centers. cCR was evaluated by findings from digital rectal examination, colonoscopy, and radiographic images. Patients in whom the watch-and-wait strategy was adopted were matched with patients who underwent radical resection through 1:1 propensity score matching analyses. Survival was calculated and compared in the two groups using the Kaplan-Meier method with the log rank test. RESULTS: A total of 117 patients in whom the watch-and-wait strategy was adopted were matched with 354 patients who underwent radical resection. After matching, there were 94 patients in each group, and no significant differences in term of age, sex, T stage, N stage or tumor location were observed between the two groups. The median follow-up time was 38.2 months. Patients in whom the watch-and-wait strategy was adopted exhibited a higher rate of local recurrences (14.9% vs. 1.1%), but most (85.7%) were salvageable. Three-year non-regrowth local recurrence-free survival was comparable between the two groups (98% vs. 98%, P = 0.506), but the watch-and-wait group presented an obvious advantage in terms of sphincter preservation, especially in patients with a tumor located within 3 cm of the anal verge (89.7% vs. 41.2%, P < 0.001). Three-year distant metastasis-free survival (88% in the watch-and-wait group vs. 89% in the surgical group, P = 0.874), 3-year disease-specific survival (99% vs. 96%, P = 0.643) and overall survival (99% vs. 96%, P = 0.905) were also comparable between the two groups, although a higher rate (35.7%) of distant metastases was observed in patients who exhibited local regrowth in the watch-and-wait group. CONCLUSION: The watch-and-wait strategy was safe, with similar survival outcomes but a superior sphincter preservation rate as compared to surgery in rectal cancer patients achieving a cCR after neoadjuvant chemoradiotherapy, and could be offered as a promising conservative alternative to invasive radical surgery.

Histopathological growth patterns correlate with the immunoscore in colorectal cancer liver metastasis patients after hepatectomy.

Various scoring systems have been proposed to predict the postoperative prognosis of colorectal liver metastasis (CRLM), including the clinical risk score (CRS), the immunoscore and so on. Recently, histopathological growth patterns (HGPs) have been recognized. However, the correlation between HGPs and the immunoscore, and their prognostic values in patients with CRLM after liver resection remain undetermined. In this study, HGPs were retrospectively evaluated in H&E-stained slides from 166 CRLM patients. The immunoscore was calculated according to the densities of immunostained CD3 + and CD8 + cells. A risk score combining HGPs, the immunoscore and the CRS was defined and divided patients into the low-, medium- and high-risk group. Our results showed that the densities of CD3 + and CD8 + cells were higher in the desmoplastic HGP (dHGP) group than in the non-dHGP group, and the proportion of high immunoscores was also higher in the dHGP group (51.9% vs. 33.0%, respectively, P = 0.020). Patients with the dHGP had significantly longer relapse-free survival (RFS) and overall survival (OS) than those with the non-HGP. The low-risk group showed significantly higher 2-year RFS and 5-year OS rates than the other two groups (RFS: 76.2%, 43.7% and 33.1%, respectively; P < 0.001; OS: 89.7%, 54.4% and 33.3%, respectively; P < 0.001). In conclusion, the dHGP correlates with relatively high immunoscores, predicting a favorable prognosis independent of the immunoscore and CRS. A novel risk score combining HGPs, the immunoscore and the CRS may be used for the stratification of CRLM patients' survival.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study / 中华医学杂志(英文版)

BACKGROUND@#Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.@*METHODS@#We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.@*RESULTS@#Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.@*CONCLUSION@#A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Expression of plasma Dickkopf-1 in patients with rheumatoid arthritis and its correlation with peripheral blood T cell subsets / 北京大学学报(医学版)

OBJECTIVE@#To detect the levels of Dickkopf-1 (DKK-1) in the plasma of patients with rheumatoid arthritis (RA), and to analyze their correlation with peripheral blood T cell subsets and clinical indicators.@*METHODS@#Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma DKK-1 levels in 32 RA patients and 20 healthy controls, and to record the various clinical manifestations and laboratory indicators of the RA patients, and flow cytometry to detect peripheral blood T cell subsets in the RA patients (Including Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4+CD161+T, CD8+T, CD8+CD161+T cells). The plasma DKK-1 levels between the two groups were ompared, and its correlation with peripheral blood T cell subsets and clinical indicators analyzed.@*RESULTS@#(1) The plasma DKK-1 concentration of the RA patients was (124.97±64.98) ng/L. The plasma DKK-1 concentration of the healthy control group was (84.95±13.74) ng/L. The plasma DKK-1 level of the RA patients was significantly higher than that of the healthy control group (P < 0.05), and the percentage of CD8+CD161+T cells in the peripheral blood of the RA patients was significantly higher than that of the healthy control group (P < 0.05). (2) The plasma DKK-1 level was positively correlated with erythrocyte sedimentation rate (r=0.406, P=0.021), DAS28 score (r=0.372, P=0.036), immunoglobulin G(r=0.362, P=0.042), immunoglobulin A(r=0.377, P=0.033); it had no correlation with age, course of disease, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibody, immunoglobulin M, complement C3, complement C4, white blood cell, neutrophil ratio. (3) The plasma DKK-1 level in the RA patients was positively correlated with the percentage of peripheral blood CD161+CD8+T cells (r=0.413, P=0.019);it had no correlation with Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4+CD161+T, CD8+T cells. (4) The percentage of CD161+CD8+T cells was negatively correlated with erythrocyte sedimentation rate (r=-0.415, P=0.004), C-reactive protein (r=-0.393, P=0.007), DAS28 score(r=-0.392, P=0.007), rheumatoid factor (r=-0.535, P < 0.001), anti-citrullinated protein antibody (r=-0.589, P < 0.001), immunoglobulin G(r=-0.368, P=0.012) immunoglobulin M (r=-0.311, P=0.035); it had no correlation with age, disease course, immunoglobulin A, complement C3, complement C4, white blood cell, and neutrophil ratio.@*CONCLUSION@#RA patients' plasma DKK-1 levels and the percentage of CD8+CD161+T cells in T cell subsets in peripheral blood increase, which may be related to the secretion of proinflammatory cytokines in patients; DKK-1 is involved in the regulation of bone homeostasis and can be used as a marker of bone destruction in RA.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study / 中华医学杂志(英文版)

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Neoadjuvant chemoradiotherapy followed by surgery in patients with unresectable locally advanced colon cancer: a prospective observational study.

BACKGROUND: The prognosis of locally unresectable colon cancer (CC) is poor. This prospective observational study aimed to further evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by surgery in these patients. PATIENTS AND METHODS: We consecutively enrolled patients who were diagnosed with locally unresectable CC from November 2010 to March 2017, and received NACRT followed by surgery. The data of all the patients were collected prospectively. The R0 resection, down-stage and pathologic complete response (pCR) rates were calculated to evaluate the short-term treatment effects. The overall survival (OS) was used to evaluate the long-term outcome. The incidence of NACRT-related acute toxicities and postsurgical complications were used to assess the safety. RESULTS: A total of 60 patients were eligible for analysis, including 57 (95.0%) patients who attained resectability after NACRT. Among patients managed with surgery, 49 cases (86.0%) achieved R0 resection, and 15 cases (26.3%) achieved pCR. Down T stage was seen in 47 cases (82.5%), and down N stage was seen in 53 cases (93.0%). After a median follow-up time of 26 months, the OS appeared as 76.7%. The most common grade 3/4 NACRT-related toxicity was myelosuppression (incidence, 20.0%). The incidence of grade 3/4 surgery-related complication was 7.0%. CONCLUSION: NACRT might be a safe and effective choice for patients with locally unresectable CC to improve treatment effects, long-term survival and life quality, though further validation is needed.

The Immunoscore system predicts prognosis after liver metastasectomy in colorectal cancer liver metastases.

BACKGROUND: The Immunoscore was initially established to evaluate the prognosis of stage I/II/III colorectal cancer patients. However, the feasibility of the Immunoscore for the prognosis of colorectal cancer liver metastases (CRCLM) has not been reported. METHODS: Liver metastases in 249 CRCLM patients were retrospectively analyzed. The Immunoscore was assessed according to the counts and densities of CD3+ and CD8+ T cells in the central- and peritumoral areas by immunohistochemistry. The prognostic role of the Immunoscore for relapse-free survival (RFS) and overall survival (OS) was analyzed with Kaplan-Meier curves and Cox multivariate models, and confirmed via an internal validation. Receiver operating characteristic (ROC) curves were plotted to compare the prognostic values of the Immunoscore and the clinical risk score (CRS) system. RESULTS: CRCLM patients with high Immunoscores (> 2) had significantly longer RFS [median RFS (95% confidence interval; 95% CI) 21.4 (7.8-35.1) vs. 8.7 (6.8-10.5) months, P < 0.001] and OS [median OS (95% CI): not reached vs. 28.7 (23.2-34.2) months, P < 0.001] than those with low Immunoscores (≤ 2). After stratification by CRS, the Immunoscore retained a statistically significant prognostic value for OS. The areas under the ROC curves (AUROCs) of the Immunoscore and the CRS system for RFS were 0.711 [95% CI 0.642-0.781] and 0.675[95% CI 0.601-0.749] (P = 0.492), whereas the AUROC of the Immunoscore system for OS was larger than that of the CRS system [0.759 (95% CI 0.699-0.818) vs. 0.660 (95% CI 0.592-0.727); P = 0.029]. CONCLUSIONS: The Immunoscore of liver metastases can be applied to predict the prognosis of CRCLM patients following liver resection.

Clinical significance of detection of soluble interleukin 2 receptor alpha chain in the assessment of rheumatoid arthritis disease activity / 北京大学学报(医学版)

OBJECTIVE@#To evaluate soluble interleukin-2 receptor alpha chain (sIL-2Rα, sCD25) in serum for the determination of rheumatoid arthritis (RA) activity.@*METHODS@#Peripheral blood was collected from 108 patients with RA, 39 patients with osteoarthritis (OA) and 50 healthy control subjects, and synovial fluids were from 40 patients with RA. The sera from the patients with RA, the disease control group (osteoarthritis), the healthy control group, and the synovial fluids of the RA patients were detected by enzyme-linked immunosorbent assay (ELISA).The clinical manifestations and laboratory parameters of the patients with RA were recorded and the correlation with the serum sCD25 level was analyzed.@*RESULTS@#The serum sCD25 concentration in RA group was (2 886±1 333) ng/L, the serum sCD25 concentration in OA group was (2 090±718) ng/L, and the serum sCD25 concentration in healthy group was (1 768±753) ng/L. The serum sCD25 level in the patients with RA was significantly higher than that in the disease controls and healthy controls (P<0.001). Sensitivity of serum sCD25 in the diagnosis of RA was 66.1% and specificity was 83.0%;serum sCD25 levels and erythrocyte sedimentation rate (r=0.321, P=0.001), C-reactive protein (r=0.446, P<0.001), DAS28 score (r=0.324, P<0.001), joint tenderness count (r=0.203, P=0.024), D-dimer levels (r=0.383, P<0.001), age (r=0.24, P=0.007), IgG (r=0.207, P=0.028), HRF-IgG (r=0.345, P=0.034) showed a significant positive correlation, and disease duration (r=-0.206, P=0.021) showed a negative correlation with sCD25;In patients with rheumatoid arthritis, the positive rates of serum ESR, CRP, and sCD25 were 14.3% (2 cases), 14.3% (2 cases), and 71.4% (10 cases) in the low disease activity group. The positive rates of serum ESR, CRP and sCD25 in the moderate disease activity group were 94.2% (49 cases), 82.7% (43 cases), and 86.5% (45 cases). The positive rates of serum ESR, CRP, and sCD25 in the high disease activity group were 100% (42 cases), 95.2% (40 cases), and 90.5% (38 cases);36 cases of ESR and/or CRP were negative (about 33.3%) in 108 patients, serum sCD5 levels of 17 cases in these 36 cases (about 47.2%)increased, of which 14 cases (about 82.4%) had a DAS28 score higher than 3.2.@*CONCLUSION@#The serum sCD25 has a high specificity for diagnosis of RA and a poor sensitivity. The serum level is closely related to the activity of RA, indicating that sCD25 may be involved in the inflammatory process of RA and may become a new inflammatory marker of RA. It is more meaningful for detection of serum sCD25 when RA is active, but ESR and/or CRP is negative.

Natural History of Seroma Following the Immediate Latissimus Dorsi Flap Method of Breast Reconstruction / 中华医学杂志(英文版)

<p><b>Background</b>The latissimus dorsi (LD) flap procedure remains a popular and useful breast reconstruction tool in China and Western countries, and donor site seroma formation is the main complication. This study was conducted in Chinese patients to determine whether stable cases of seromas would resolve without treatment.</p><p><b>Methods</b>A.</p><p><b></b>retrospective review of 45 consecutive cases of immediate breast reconstruction with LD flap from April 2012 to February 2017 was conducted. The scope of the seroma was demarcated with a marker pen, and cases that remained stable over time (i.e. the size of the seroma did not increase) were observed without treatment. The measured outcomes included the incidence of seromas, the volume and duration of postoperative wound drainage, and other demographic characteristics.</p><p><b>Results</b>Twenty-four patients (53.3%) developed a seroma at the donor site. Of these, 21 patients (87.5%) did not require treatment, and the seroma resolved over time. The mean duration of a sustained seroma was 6.8 ± 1.4 weeks (range: 4-9 weeks).</p><p><b>Conclusions</b>This study observed the scope and progression of the seromas and found that seromas at the LD donor sites resolved over time without treatment.</p>

Safety of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection: a randomized, multicenter, prospective, phase III IOCCRC trial (IOCCRC).

PURPOSE: The safety and efficacy of intraoperative chemotherapy in colorectal cancer have not yet been extensively investigated. This randomized control trial was designed to compare the safety and efficacy of intraoperative chemotherapy in combination with surgical resection to those of traditional surgical resection alone. METHODS: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled in this study: 341 patients were randomly assigned to the intraoperative chemotherapy, which consist of portal vein chemotherapy, intraluminal chemotherapy and intraperitoneal chemotherapy, plus surgery group, whereas 344 patients were randomized to the control group to undergo surgery alone. Eleven patients withdrew consent. RESULTS: Intraoperative chemotherapy did not increase the rate of surgical complications, and no severe chemotherapy-associated side effects were observed. Four patients in each of the intraoperative chemotherapy and the control groups experienced anastomotic leakage and underwent a second operation (1.2 vs. 1.2%, P = 0.99). There were no deaths within 90 days after surgery in the chemotherapy group, whereas one patient died in the control group. Intraoperative chemotherapy did not decrease the rate of patients who received postoperative chemotherapy between the intraoperative group and control group (29.3 vs. 30.2%, P = 0.795). CONCLUSIONS: Intraoperative chemotherapy can be safely performed during colorectal surgery; however, follow-up is necessary for a better assessment of its efficacy. ClinicalTrial.gov Register Number: NCT01465451.

The renal safety and efficacy of combined gemcitabine plus cisplatin and gemcitabine plus carboplatin chemotherapy in Chinese patients with a solitary kidney after nephroureterectomy.

PURPOSE: The renal safety of cisplatin-based chemotherapy has not been investigated in patients with urothelial carcinoma of the upper urinary tract (UUT-UC) who retain a solitary kidney after nephroureterectomy. This study aimed to assess and compare the renal safety and efficacy of gemcitabine-cisplatin (GP) and gemcitabine-carboplatin (GC) in these patients. METHODS: The medical records of patients diagnosed with urothelial carcinoma at the Sun Yat-Sen University Cancer Center between January 2005 and December 2015 were retrospectively reviewed. The creatinine clearance (CrCl) and estimated glomerular filtration rate (eGFR) were used to assess renal function and were calculated using different formulas. RESULTS: A total of 71 patients were enrolled in this study; 48 patients were on GP, and 23 were on GC. The renal function indicators (CrCl and eGFR) were all significantly lower after GP chemotherapy than at baseline, a phenomenon that was not observed in the GC group. Severe nephrotoxicities (SNTs) were reported in 12 patients on GP (25%) and zero on GC. SNT risk factors included a more than 20% decrease in eGFR after one GP cycle and the presence of diabetes (all p < 0.05). Among patients treated with first-line palliative chemotherapy (n = 32), GC (n = 13) patients had an ORR of 46.2%, which was not significantly different from GP patients (36.8%, n = 19), whereas GC patients tended to have a shorter OS than GP patients (9.2 vs. 29 months, p = 0.200). CONCLUSIONS: Our results confirm that GP has an adverse impact on the renal function of patients with UUT-UC who retain a solitary kidney, but it can be safely administered to the majority of these patients without inducing SNT. In specific patients, GC is an alternative to GP that has comparable efficacy and favourable renal toxicity.