[Correlation between serum growth differentiation factor 11 level and severity of coronary artery disease in patients with acute myocardial infarction].

Objective: To investigate the correlation between serum growth differentiation factor 11 (GDF11) level and coronary artery lesions in patients with ST-segment elevation myocardial infarction (STEMI), and the predictive efficacy of nomogram risk prediction model based on GDF11 combined with traditional risk factors on the occurrence of STEMI. Methods: This study was a retrospective cross-sectional study. Patients hospitalized in the Department of Cardiology of the 904th Hospital of Joint Logistic Support Force of People's Liberation Army of China from 2016 to 2018 were selected and divided into control group and STEMI group. The demographic data, blood lipid level, laboratory indicators of blood and GDF11 level were collected. Logistic regression analysis screened out independent correlated factors for the occurrence of STEMI. Spearman correlation analysis clarified the correlation of each indicator with the SYNTAX or Gensini scores. A nomogram risk prediction model for the risk of STEMI occurrence and the receiver operating characteristic curve was used to compare the prediction efficiency of each model. Results: A total of 367 patients were enrolled, divided into control group (n=172) and STEMI group (n=195), age (66.5±11.8), male 222 (60.49%). The serum GDF11 level of STEMI group was significantly lower than that of the control group (36.20 (16.60, 70.75) µg/L vs. 85.00 (53.93, 117.10) µg/L, P<0.001). The results of multivariate logistic regression analysis showed serum GDF11(OR=0.98, 95%CI: 0.97-0.99) and traditional independent risk factors such as smoking, diabetes, C-reactive protein, homocysteine, lipoprotein (a) and apolipoprotein A1/B were independent correlate factors for the occurrence of STEMI (P<0.05). Spearman correlation analysis showed that serum GDF11 was negatively correlated with SYNTAX score and Gensini score (P<0.05). The nomogram model constructed by serum GDF11 combined with traditional independent risk factors (AUC=0.85, 95%CI: 0.81-0.89) had better predictive value for the occurrence of STEMI than the traditional nomogram model constructed by independent risk factors(AUC=0.80, 95%CI:0.75-0.84) or serum GDF11 (AUC=0.76, 95%CI: 0.72-0.81), all P<0.01. Conclusions: Serum GDF11 is an independent correlate factor in the occurrence of STEMI and is negatively correlated with the severity of coronary artery lesions in patients with STEMI. The nomogram model constructed based on GDF11 combined with traditional risk factors can be a good predictor for the occurrence of STEMI.

Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.

BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study.

AIMS: Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation. MATERIALS AND METHODS: In total, 36 eligible participants experiencing SCLC transformation from EGFR-mutant NSCLC will be enrolled to receive combination therapy of serplulimab, etoposide and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab for up to 2 years. The primary endpoint is progression-free survival; secondary endpoints include objective response rate, overall survival and safety. RESULTS: Enrolment started in July 2023 and is ongoing, with an estimated completion date of December 2025. CONCLUSIONS: This study aims to provide valuable insights into the efficacy and safety of combining serplulimab with chemotherapy for treating patients with T-SCLC originating from EGFR-mutant NSCLC.

[Epidemiological characteristics of mpox epidemic in Guangzhou].

Objective: To understand the epidemiological characteristics of mpox epidemic in Guangzhou and provide scientific evidence for the prevention and control of the disease. Methods: Based on the mpox surveillance system in Guangzhou, suspected mpox cases with fever and rash were reported by local hospitals at all levels to centers for disease control and prevention in Guangzhou for sampling, investigation and diagnosis. Descriptive epidemiological analysis was conducted on the clinical characteristics and treatment of the mpox cases and positive detection rate reported in Guangzhou as of 24:00 on June 23. Whole genome sequencing of the virus isolates was performed using Illumina Miniseq high-throughput sequencing platform. Results: The first mpox case in Guangzhou was reported on June 10 in 2023. As of 24:00 on June 23, a total of 25 confirmed mpox cases were reported. All the mpox cases were men with a M(Q1,Q3) of 32 (26, 36) years, the majority of the cases were MSM (96.0%). The main clinical features were rash (100.0%, 25/25), lymphadenectasis (100.0%, 25/25) and fever (52.0%, 13/25). Rash usually occurred near the genitals (88.0%, 22/25). The close contacts, mainly family members (40.4%, 23/57), showed no similar symptoms, such as fever or rash. The positive rate of mpox virus in household environment samples was 30.5%. The analyses on 3 complete gene sequences of mpox virus indicated that the strains belonged to West African type Ⅱb clade, B.1.3 lineage. Conclusions: Hidden transmission of mpox virus had occurred in MSM in Guangzhou. However, the size of affected population is relatively limited, and the possibility of wide spread of the virus is low.

[The impact of human umbilical cord-derived mesenchymal stem cells on the pancreatic function of type 2 diabetic mice and their regulatory role on NLRP3 inflammasomes].

Objective: To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice. Methods: Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group (n=5) and a high-fat feeding modeling group (n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group (n=7) and a UC-MSCs treatment group (n=7). The UC-MSCs treatment group was given UC-MSCs (1×106/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1ß (IL-1ß) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1ß in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results: In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1ß decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1ß secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3ß (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions: UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.

Ethics and biomedical engineering for well-being: a cocreation study of remote services for monitoring and support.

The well-being of students and staff directly affects their output and efficiency. This study presents the results of two focus groups conducted in 2022 within a two-phase project led by the Applied Biomedical and Signal Processing Intelligent e-Health Lab, School of Engineering at the University of Warwick, and British Telecom within "The Connected Campus: University of Warwick case study" program. The first phase, by involving staff and students at the University of Warwick, aimed at collecting preliminary information for the subsequent second phase, about the feasibility of the use of Artificial Intelligence and Internet of Things for well-being support on Campus. The main findings of this first phase are interesting technological suggestions from real users. The users helped in the design of the scenarios and in the selection of the key enabling technologies which they considered as the most relevant, useful and acceptable to support and improve well-being on Campus. These results will inform future services to design and implement technologies for monitoring and supporting well-being, such as hybrid, minimal and even intrusive (implantable) solutions. The user-driven co-design of such services, leveraging the use of wearable devices and Artificial Intelligence deployment will increase their acceptability by the users.

[Clinical and genetic characteristics of young patients with myeloproliferative neoplasms].

Objectives: To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN). Methods: In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients. Results: 1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion: Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

A phase II open-label trial of avelumab plus axitinib in previously treated non-small-cell lung cancer or treatment-naïve, cisplatin-ineligible urothelial cancer.

BACKGROUND: We hypothesized that avelumab plus axitinib could improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC) or urothelial carcinoma (UC). PATIENTS AND METHODS: We enrolled previously treated patients with advanced or metastatic NSCLC, or untreated, cisplatin-ineligible patients with advanced or metastatic UC. Patients received avelumab 800 mg every 2 weeks (Q2W) and axitinib 5 mg orally two times daily. The primary endpoint was objective response rate (ORR). Immunohistochemistry was used to assess programmed death-ligand 1 (PD-L1) expression (SP263 assay) and the presence of CD8+ T cells (clone C8/144B). Tumor mutational burden (TMB) was assessed by whole-exome sequencing. RESULTS: A total of 61 patients were enrolled and treated (NSCLC, n = 41; UC, n = 20); 5 remained on treatment at data cut-off (26 February 2021). The confirmed ORR was 31.7% in the NSCLC cohort and 10.0% in the UC cohort (all partial responses). Antitumor activity was observed irrespective of PD-L1 expression. In exploratory subgroups, ORRs were higher in patients with higher (≥median) CD8+ T cells in the tumor. ORRs were higher in patients with lower TMB (

[Clinical characteristics and progression risk factors for patients with monoclonal gammopathy of undetermined significance].

Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.

[Research progress on drug resistance of anti-varicella-zoster virus drugs].

Varicella-zoster virus (VZV) causes chickenpox when it first infects humans, and the virus may reactivate in adulthood and cause herpes zoster (HZ). Broad-spectrum antiviral drugs are one of the treatments for varicella and herpes zoster, but the emergence of drug resistance poses many challenges to this treatment and increases the burden of disease on patients. This paper discusses the resistance mechanisms, resistance sites and resistance detection methods of anti-VZV drugs in order to help further research on new anti-VZV targets, new drugs and monitoring of resistance to existing drugs.

Prevalence and Risk Factors of Frailty in Stroke Patients: A Meta-Analysis and Systematic Review.

OBJECTIVES: Summarize the existing evidence regarding the prevalence and risk factors of frailty in stroke patients. DESIGN: A meta-analysis and systematic review. PARTICIPANTS: Stroke patients in hospitals or communities. METHODS: We undertook a systematic review and meta-analysis using articles available in 8 databases, including PubMed, The Cochrane Library, Web of Science, Embase, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Weipu Database (VIP) from January 1990 to April 2022. Studies were quality rated using the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality tool. RESULTS: A total of 24 studies involving 30,423 participants were identified. The prevalence of frailty and pre-frailty in stroke patients was 27% (95%CI: 0.23-0.31) and 47.9% (95%CI: 0.43-0.53). Female gender (OR = 1.76, 95%CI: 1.63-1.91), advanced age (MD = 6.73, 95%CI: 3.55-9.91), diabetes (OR = 1.34, 95%CI: 1.06-1.69), hyperlipidemia (OR = 1.46, 95%CI: 1.04-2.04), atrial fibrillation (OR = 1.36, 95%CI: 1.01-1.82), National Institutes of Stroke Scale (NIHSS) admission scores (MD = 2.27, 95%CI: 1.72-2.81) were risk factors of frailty in stroke patients. CONCLUSIONS: Frailty was more prevalent in stroke patients. Female gender, advanced age, diabetes, hyperlipidemia, atrial fibrillation, and National Institutes of Stroke Scale (NIHSS) admission scores were identified as risk factors for frailty in stroke patients. In the future, medical staff should pay attention to the early screening of frailty in high-risk groups and provide information on its prevention.

[IgG4-related diseases of retroperitoneum in urinary and male reproductive system: a clinicopathological analysis of eleven cases].

Objective: To analyze the clinicopathological features of IgG4-related diseases (RD) of retroperitoneum and the urinary and male reproductive system (IgG4-RUMR). Methods: A total of 11 IgG4-RUMR cases from January 2013 to March 2021 were retrospectively collected at Peking University Third Hospital and Shandong Provincial Hospital affiliated to Shandong First Medical University. The clinicopathologic features, laboratory and imaging findings were analyzed and scored according to the 2019 ACR/EULAR classification criteria for IgG4-RD. Results: The 11 patients (male:female is 9∶2; mean age 59 years, range from 44 to 83 years) were initially admitted to the Deparment of Urology/Kidney Transplantation (10 cases) and the Department of Oncology (1 case). All patients had urogenital disorders or imaging abnormalities. Three of the 11 patients had a history of IgG4-RD such as lacrimal gland engorgement, salivary gland engorgement and IgG4-associated pancreatitis. Abnormal retroperitoneal soft tissue and hydronephrosis were found in eight cases, while epididymal and spermatic cord masses were found in one case, simple renal mass in one case, and"benign prostatic hyperplasia"in one case. In the 10 patients tested for serum IgG4, the serum IgG4 level was 0.8-14.4 g/L. Histologically, all cases showed significant lymphoplasmacytic infiltration and storiform fibrosis, and some were accompanied by obliterative phlebitis. The number of IgG4 positive plasma cells was 12-155 per high-power field, and the IgG4/IgG ratio was 15%-77%. According to the 2019 ACR/EULAR IgG4-RD classification standard 11 cases scored 20-48 points, all of which met the diagnostic criteria of IgG4-RUMR. Therapeutically, the patient with a simple renal mass underwent partial nephrectomy. The patient with prostate lesion underwent transurethral resection of prostate and was initially diagnosed as nonspecific chronic prostatitis. Later, the patient was admitted again because of salivary gland swelling, and the pathologic diagnosis was amended. The patient with epididymal and spermatic cord masses participated in a clinical trial about retroperitoneal fibrosis. The remaining eight patients received symptomatic treatment such as adhesiolysis and stent placement. All the patients were subsequently treated with glucocorticoid/immunosuppressant and symptoms relieved. Conclusions: IgG4-RUMR is uncommon. In clinical practice, information from clinical, serologic, radiologic and pathologic evaluations must be integrated. IgG4-RUMR should be considered in the differential diagnosis of urinary and male reproductive diseases. The 2019 ACR/EULAR classification criteria for IgG4-RD, while relatively complex, are objective and practical in the diagnosis of IgG4-RUMR.

Synergistically enhanced ultraviolet emission of Yb doped ZnO films by using a capping of ultrathin Al and SiO2 microspheres.

We studied the enhancement effects of ultraviolet (UV) emission from rare earth ytterbium (Yb) doped ZnO films, by using capping layers of Al and SiO2 micro-spheres. The films were deposited on Si substrates with magnetron sputtering followed by high temperature (∼1000°C) heat treatment, and then capped with a nanoscale ultrathin aluminum (Al) layer and/or SiO2 micro-spheres on the surface of the films. The photoluminescence (PL) results indicate that compared to the case without any capping, the UV emission is enhanced by a factor ranging from several to dozens times, the films capped with 2.0 nm Al layer and 5.0 µm SiO2 microspheres have the longest highest PL intensity among the samples. The PL enhancements are discussed in terms of increased optical (or electrical) fields around the surface of the films combined with defect passivation after the capping. Our work has proposed a strategy to enhance the UV emissions of ZnO, which will broaden the application potential of ZnO in UV photonics.

[Prognostic value of translocation t(11;14) in primary light-chain amyloidosis treated with bortezomib-based regimen].

Objective: To investigate the prognostic value of translocation t(11;14) in newly-diagnosed primary light-chain (AL) amyloidosis patients treated with bortezomib-based regimen. Method: Clinical information of newly-diagnosed AL amyloidosis patients in Peking Union Medical College Hospital who had baseline t(11;14) data and accepted bortezomib-combined therapies from September, 2015 to September, 2021 was collected. The relationships between t(11;14) status and baseline characteristics, hematological response, organ response and prognosis were analyzed. Results: A total of 152 patients were included, aged (59.5±9.1) years and 93 cases were male (61.2%). Forty-six patients carried t(11;14) (30.3%). There was no statistical difference in the proportion of organ involved, distribution of Mayo 2004 and 2012 stages and laboratory indexes between patients with and without t(11;14) (all P>0.05). For hematological response, the difference in the rates of ≥very good partial response (VGPR) between those with t(11;14) and without after the first cycle [28.2%(11/39) vs 37.4%(34/91), P>0.05] was not statistically significant. After 3 cycles, the difference in the rates of ≥VGPR between two groups was not statistically significant [35.9%(14/39) vs 51.1%(46/90), P>0.05]. The difference in the ratio of the best hematological response reaching ≥VGPR between two groups during the first-line treatment was not statistically significant [52.2%(24/46) vs 64.2%(68/106), P>0.05]. But patients with t(11;14) had lower cardiac response rate at 3 months [15.2%(5/33) vs 34.6%(28/81), P=0.038] and 6 months [19.4%(6/31) vs 50.6%(42/83),P=0.003] than those without, but the difference in cardiac response rates at 12 months was not statistically significant [41.7%(10/24) vs 53.5%(38/71),P>0.05]. For survival, the differences in overall survival (not reached vs 50.1 months, P>0.05) and hematological event-free survival (36.2 months vs 39.9 months, P>0.05) between patients carrying t(11;14) and those without were not statistically significant. Conclusion: Patients with t(11;14) had lower cardiac response rate than those without, but their hematological response and survival are not significantly different from those free from t(11;14).

[Analysis on epidemiological characteristics of dengue fever and E gene evolution of dengue virus in Guangzhou, 2020].

Objective: To assess the incidence of dengue fever and E gene evolution of dengue virus in Guangzhou in 2020 and understand the local epidemiological characteristics of dengue fever and spreading of dengue virus. Methods: The information of dengue fever cases in Guangzhou in 2020 was collected from Notifiable Infectious Disease System of Chinese Center for Disease Control and Prevention Information System. Serum samples from the cases were detected by real-time PCR. The E gene was sequenced and analyzed. Maximum likelihood phylogenetic trees were constructed using software MEGA 5.05. The statistical analysis was conducted using software SPSS 20.0. Results: A total of 33 dengue fever cases were reported in Guangzhou in 2020, including 31 (93.94%) imported cases and 2 (6.06%) local cases. Compared with the data during 2016 to 2019, the number of cases, overall incidence and local incidence all decreased with statistically significant differences (all P<0.05). The imported cases from Southeast Asia constituted 90.32% (28/31) of imported cases. The E gene sequences and the phylogenetic trees of imported and local cases demonstrated close relationship with the virus sequences from Southeast Asian, and they were less homologous with the sequences of dengue virus isolated in Guangzhou in previous years. Conclusions: The incidence of dengue in Guangzhou in 2020 was significantly affected by the imported cases, especially those from Southeast Asian countries. The study result demonstrated that dengue fever was not endemic in Guangzhou and it was caused by imported ones.

Treatment-related adverse events as predictive biomarkers of efficacy in patients with advanced neuroendocrine tumors treated with surufatinib: results from two phase III studies.

BACKGROUND: No validated biomarkers currently exist for predicting the efficacy outcomes in patients with neuroendocrine tumors (NETs) treated with antiangiogenic therapy. We aimed to evaluate the association between treatment-related adverse events (TRAEs) and efficacy outcomes of surufatinib in patients with advanced NET. PATIENTS AND METHODS: We included patients with NET treated with surufatinib in two multicenter, randomized, double-blind, placebo-controlled, phase III trials (SANET-p and SANET-ep) in this study. The main exposure was the presence of any of the TRAEs including hypertension, proteinuria, and hemorrhage in the first 4 weeks of surufatinib treatment. The primary outcome of the study was investigator-assessed progression-free survival (PFS). PFS outcomes were estimated using the Kaplan-Meier method with the log-rank test. Hazard ratios (HRs) were calculated by using univariable and multivariable Cox proportional hazard regression models. Blinded independent image review committee (BIIRC) assessments and 4-week landmark analysis were also performed as supportive evaluations. RESULTS: During the study period, a total of 242 patients treated with surufatinib were included in the analysis, and 164 (68%) patients had at least one of hypertension, proteinuria, and hemorrhage in the first 4 weeks of treatment. The presence of TRAEs in the first 4 weeks was associated with prolonged median PFS [11.1 versus 9.2 months; HR 0.67, 95% confidence interval (CI) 0.47-0.97; P = 0.036]. In multivariable Cox regression analysis, the presence of TRAEs was also significantly associated with longer PFS (HR 0.65, 95% CI 0.44-0.97; P = 0.035). Similar results were obtained in the BIIRC assessments and 4-week landmark analysis. CONCLUSIONS: Treatment-related hypertension, proteinuria, and hemorrhage could be potential biomarkers to predict antitumor efficacy of surufatinib in patients with advanced NET. Future prospective studies are needed to validate the findings. TRIAL REGISTRATION: ClinicalTrials.govNCT02589821; https://clinicaltrials.gov/ct2/show/NCT02589821 and ClinicalTrials.gov NCT02588170; https://clinicaltrials.gov/ct2/show/NCT02588170.

[Efficacy and safety of daratumumab in the treatment of advanced light chain amyloidosis].

Objective: The study investigated the efficacy and safety of daratumumab in the treatment of cardiac light chain (AL) amyloidosis. Methods: We retrospectively analyzed the clinical characteristics, hematologic response, organ response, long-term survival, and adverse events of 20 patients with newly diagnosed or relapsed/refractory cardiac AL amyloidosis treated with daratumumab in Peking Union Medical College Hospitalo from January 2017 to March 2021. Results: The overall median age of 20 patients was 62 (range, 45-73) yeas, with a male to female ratio of 2.3:1. Nine patients were newly diagnosed, while 11 patients had relapsed or refractory disease. Based on Mayo 2004 cardiac AL staging system, stages Ⅱ and Ⅲ diseases were present in 20 patients respectively. Four patients died during the first cycle of daratumumab, and the remaining 16 patients completed a median of 3 (range, 1-10) cycles of treatment. Overall hematologic response rates were 80% each at 1, 3, and 6 months after treatment initiation, and 45% , 60% , and 60% of the patients achieved at least a very good partial response at 1, 3, and 6 months respectively. The median duration to hematologic response was 13 (range, 6-28) days. At 3, 6, and 12 months, 20% , 30% , and 40% of the patients respectively achieved a cardiac response, and the median days to response was 91 (range, 30-216) days. As of the last follow-up, 9 (45% ) patients died. The 1-month mortality rate of all the patients and stage IIIb patients was 25% and 40% , respectively. The 1-year overall survival rate was 48.4% . Lymphocytopenia was the most common hematological adverse event (above grade 3) . Non-hematological adverse events were mainly infusion-related reactions and infections. Conclusion: Daratumumab could induce deep and rapid hematologic response in newly diagnosed and previously treated cardiac AL amyloidosis patients. However, daratumumab was not effective in preventing the high and early mortality rate in stage Ⅲb patients.