Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males. Immune-checkpoint inhibitors (ICIs) that target programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive efficacy in the treatment of non-small-cell lung cancer (NSCLC) (Pardoll, 2012; Champiat et al., 2016; Gao et al., 2022). Although ICIs are usually well tolerated, they are often accompanied by immune-related adverse events (irAEs) (Doroshow et al., 2019). Non-specific activation of the immune system produces off-target immune and inflammatory responses that can affect virtually any organ or system (O'Kane et al., 2017; Puzanov et al., 2017). Compared with adverse events caused by chemotherapy, irAEs are often characterized by delayed onset and prolonged duration and can occur in any organ at any stage of treatment, including after cessation of treatment (Puzanov et al., 2017; von Itzstein et al., 2020). They range from rash, pneumonitis, hypothyroidism, enterocolitis, and autoimmune hepatitis to cardiovascular, hematological, renal, neurological, and ophthalmic irAEs (Nishino et al., 2016; Kumar et al., 2017; Song et al., 2020). Hence, we conducted a retrospective study to identify validated factors that could predict the magnitude of the risk of irAEs in patients receiving PD-1/PD-L1 inhibitors; our approach was to analyze the correlation between the clinical characteristics of patients at the start of treatment and relevant indicators such as hematological indices and the risk of developing irAEs. Then, we developed an economical, practical, rapid, and simple model to assess the risk of irAEs in patients receiving ICI treatment, as early as possible.
Male ; Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/adverse effects* ; Programmed Cell Death 1 Receptor ; Retrospective Studies ; Apoptosis

Objective:To evaluate the efficacy and safety of of rivaroxaban for different doses in the treatment of isolated distal deep vein thrombosis.Methods:The clinical data of 853 patients of isolated distal deep vein thrombosis attending Nanjing Drum Tower Hospital from Jan 2018 to Dec 2020 was retrospectively analyzed.Results:Thrombotic recurrence rate increased with increasing follow-up in the standard and low dose groups, and it was significantly lower in the standard dose group than in the low dose group (HR=0.44, 95% CI: 0.25-0.78, P=0.005) with most thrombosis occurring within the first year of follow-up. There was no statistical difference between the two groups in terms of major bleeding events (HR=1.70,95%CI 0.56-5.14, P=0.530) and the incidence of clinically relevant non-major bleeding events was significantly higher in the standard dose group than in the low dose group (HR=2.36, 95%CI 1.26-4.44, P=0.020). Subgroup analysis on anticoagulation duration found when anticoagulation duration was longer than 1.5 months, the risk of thrombosis was lower in the standard dose group than the low dose group (1.5-3 months:HR=0.11, 95%CI 0.01-0.87, >3 months: HR=0.19, 95%CI 0.04-0.95), there was an interaction between anticoagulation duration and dose ( P=0.007). Conclusions:Based on the risk of thrombosis recurrence and bleeding events, the standard dose of rivaroxaban (20 mg qd) is recommended for patients with isolated distal deep vein thrombosis, and the anticoagulant duration should be maintained for 1.5 months or more.

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Objective: To describe the prevalence of home blood pressure monitoring and analyze the factors influencing regular blood pressure monitoring among elderly uncontrolled hypertensive patients in Central and Western China. Methods: It was a cross-sectional study, which enrolled hypertensive patients aged over 60 years with office blood pressure ≥140/90 mmHg (1 mmHg=0.133 kPa) from September 2019 to July 2020 in 72 hospitals in Central and Western China. Patients completed the electronic questionnaires, and were divided into regular and irregular home blood pressure monitoring groups. The proportion of patients using different types of sphygmomanometers and the percentage of patients with regular home blood pressure monitoring (at least weekly) were explored. The generalized linear mixed model was used to define the influencing factors of regular home blood pressure monitoring. Results: A total of 3 857 patients were included in this study. Age was 67(64,71) years old and there were 2 163 males (56.1%). Overall, sphygmomanometer was available at home for 3 044(78.9%) patients, 2 168(56.2%) patients conducted regular home blood pressure monitoring. Among the patients with a sphygmomanometer at home, 2 370(77.9%) of the sphygmomanometers were upper arm electronic device. Older age, higher income, longer history of hypertension, multiple antihypertensive medications and awareness of diagnostic criteria of hypertension and hypertension complications were associated with a higher prevalence of regular home blood pressure monitoring (all P<0.05). Conclusions: Among the elderly hypertensive patients with uncontrolled blood pressure in Central and Western China, there is a relatively high prevalence of home sphygmomanometer ownership and regular monitoring. Age, family income, history of hypertension, number of antihypertensive drugs and knowledge of hypertension are the influencing factors of regular home blood pressure monitoring in this population.
Aged ; Male ; Humans ; Middle Aged ; Blood Pressure Monitoring, Ambulatory ; Antihypertensive Agents/therapeutic use* ; Cross-Sectional Studies ; Hypertension/drug therapy* ; Blood Pressure ; China/epidemiology*

Objective: To explore and compare the effect of standard or prolonged dual antiplatelet therapy (DAPT) on the long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus after drug-eluting stent (DES) implantation. Methods: Consecutive patients with diabetes mellitus, ≥65 years old, underwent DES implantation, and had no adverse events within 1 year after operation underwent percutaneous coronary intervention (PCI) from January to December 2013 in Fuwai Hospital were enrolled in this prospective cohort study. These patients were divided into three groups according to DAPT duration: standard DAPT duration group (11 ≤ DAPT duration≤ 13 months) and prolonged DAPT duration group (1324 months). All the patients were followed up at 1, 6 months, 1, 2 and 5 years in order to collect the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), and type 2 to 5 bleeding events defined by the Federation of Bleeding Academic Research (BARC). MACCE were consisted of all cause death, myocardial infarction, target vessel revascularization or stroke. The incidence of clinical adverse events were compared among 3 different DAPT duration groups, and Cox regression model were used to analyze the effect of different DAPT duration on 5-year long-term prognosis. Results: A total of 1 562 patients were enrolled, aged (70.8±4.5) years, with 398 female (25.5%). There were 467 cases in standard DAPT duration group, 684 cases in 1324 months group. The patients in standard DAPT duration group and the prolonged DAPT duration groups accounted for 29.9% (467/1 562) and 70.1% (1 095/1 562), respectively. The 5-year follow-up results showed that the incidence of all-cause death in 13P=0.011) and DAPT duration>24 month group(4.1%(17/411) vs. 8.6%(40/467),P=0.008) were significantly lower than in standard DAPT group. The incidence of myocardial infarction in 13P=0.002). The incidence of MACCE in 1324 month group were 19.3% (90/467), 12.3% (84/684), 20.2% (83/411), respectively, P<0.001). There was no significant difference in the incidence of stroke and bleeding events among the three groups (all P>0.05). Multivariate Cox analysis showed that compared with the standard DAPT group, prolonged DAPT to 13-24 months was negatively correlated with MACCE (HR=0.601, 95%CI 0.446-0.811, P=0.001), all-cause death (HR=0.568, 95%CI 0.357-0.903, P=0.017) and myocardial infarction (HR=0.353, 95%CI 0.179-0.695, P=0.003). DAPT>24 months was negatively correlated with all-cause death (HR=0.687, 95%CI 0.516-0.913, P=0.010) and positively correlated with revascularization (HR=1.404, 95%CI 1.116-1.765, P=0.004). There was no correlation between prolonged DAPT and bleeding events. Conclusions: For elderly patients with coronary heart disease complicated with diabetes mellitus underwent DES implantation, and had no MACCE and bleeding events within 1 year after operation, appropriately prolonging of the DAPT duration is related to the reduction of the risk of cardiovascular adverse events. Patients may benefit the most from the DAPT between 13 to 24 months. In addition, prolonging DAPT duration does not increase the incidence of bleeding events in this patient cohort.
Aged ; Coronary Artery Disease/surgery* ; Diabetes Mellitus ; Drug Therapy, Combination ; Drug-Eluting Stents/adverse effects* ; Female ; Hemorrhage ; Humans ; Male ; Myocardial Infarction/epidemiology* ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Prognosis ; Prospective Studies ; Stroke ; Treatment Outcome

Objective: To explore the related factors of premature acute myocardial infarction(AMI), and to compare the the long-term outcomes in patients with and without premature AMI after percutaneous coronary intervention (PCI). Methods: This study was a prospective cohort study.From January 2013 to December 2013, 10 724 consecutive patients with coronary heart disease undergoing PCI in Fuwai Hospital were enrolled. Among them 1 920 patients with the diagnosis of AMI were divided into two groups: premature AMI (man≤50 years old, woman≤60 years old) and non-premature AMI. The baseline characteristics were collected, and multivariate logistic regression was uesed to analysis the related factors of premature AMI. The clinical outcomes, including the major adverse cardiovascular and cerebrovascular events(MACCE) which was the composite of cardiac death, myocardial infarction, revascularization, stroke and stent thrombosis, as well as bleeding events, during hospitalization, at 2 years and 5 years follow-up were analyzed. Results: A total of 1 920 AMI patiens were included(age was (56.5±11.3) years old)，with 1 612(84.0%) males. There were statistically significant differences between the two groups in gender, body mass index, blood lipid, complications, inflammatory markers, etc (all P<0.05). Multivariate logistic regression analysis showed body mass index(OR=1.06, 95%CI 1.01-1.10, P<0.01), triglyceride(OR=1.47, 95%CI 1.14-1.90, P<0.01), serum uric acid level(OR=1.02, 95%CI 1.01-1.04, P<0.01), high density lipoprotein cholesterol level(OR=0.33, 95%CI 0.14-0.78, P=0.01) and history of hypertension(OR=0.72, 95%CI 0.56-0.93, P=0.01) were independent related factors of premature AMI. The incidence of all-cause death and cardiac death were lower during hospitalization, at 2 years and 5 years follow-up in the premature AMI group than in non-premature AMI group(all P<0.05). In the premature AMI group, the incidence of MACCE and stroke was lower, with more bleeding events in 5 years follow-up(all P<0.05). Conclusions: Metabolic abnormalities, including high BMI, high triglyceride level and high serum uric acid, low high-density lipoprotein cholesterol level are the related factor of premature AMI. The incidence of ischemic events in patients with premature AMI is lower, while the incidence of bleeding events is higher than non-premature AMI patients.
Aged ; Coronary Artery Disease ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Prospective Studies ; Risk Factors ; Treatment Outcome ; Uric Acid

Objective: To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. Methods: The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed. Results: 92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M(3)) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×10(9)/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients' partner genes weren't identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (P<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (P=0.688). Multivariate analysis revealed that high WBC (RR=1.825, 95% CI 1.022-3.259, P=0.042), one cycle to achieve CR (RR=0.130, 95% CI 0.063-0.267, P<0.001), post-remission treatment with allo-HSCT (RR=0.169, 95% CI 0.079-0.362, P<0.001) were independent prognostic factors affecting OS. Conclusions: AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.
Adolescent ; Adult ; Aged ; Gene Rearrangement ; Hematopoietic Stem Cell Transplantation ; Histone-Lysine N-Methyltransferase ; Humans ; Leukemia, Myeloid, Acute ; Middle Aged ; Myeloid-Lymphoid Leukemia Protein ; Prognosis ; Retrospective Studies ; Young Adult

OBJECTIVETo performe the immuneserological and RHD Genotype analyses for DVI type 3 genotype pregnemt women with anti-D.

METHODSRhD blood type of this pregnant women was identified by common serological methods, then the blood group specific antibodies was screened and identified; the polymerase chain reaction-sequence specific primer(PCR-SSP) was used to identify the pregnant women's RHD genotype; RhD blood group for the pregnant women, her spouse and daughter was genogrouped and genetically analyzed by multiplex ligation-dependent probe amplification(MLPA). The heredity of this family was analyzed finally.

RESULTSThe titer of IgG anti-D in the pregnant woman serum was 1:8; the PCR-SSP showed that the 3rd to 6th exons of RHD gene were missing in the pregnant woman. the genotype of pregnant woman was identified as DVI type 3; the MLPA analysis showed that this pregnant women owned only one RHD allele with 3rd to 6th exons missed, and her genotype was identified as CDe/cde; her spouse was identified as CDe/CDe homozygous genotype, and her daughter as CDe/CDe.

CONCLUSIONAccurate identification of RhD blood type is of great significance for a safe and effective clinical blood transfusion strategy, and for taking appropriate measures to prevent hemolytic disease of newborn (HDN) at women childbearing age.

OBJECTIVETo explore the phenotype types and genetic mutation mechanism of Rhesus D variant individuals.

METHODSFouty-eight peripheral blood samples of pregnancies and blood donors who had been identified as Rhesus D variant by using routine serologic methods were collected from January 2013 to October 2015 in our center. The multiple ligation-dependent probe amplification(MLPA) was used to determine the RHD after genomic DNA had been extracted from the blood sample, then the data including gene copy number variations, point mutations, deletions and hybrid fusions were analyzed by GeneMarker software. All exons of blood sample RHD were amplified via PCR and analyzed by sequencing when its MLPA results were not in accordance with serologic results. Cloning and haplotype sequencing were performed if novel allele had been found.

RESULTSRh phenotypes of the 48 samples were typed as following: 20 cases out of 48 were CcDee(41.7%, 20/48),12 cases were ccDEe (25%,12/48), 11 cases were CCDee(22.9%, 11/48), 5 cases were CcDEe (10.4%, 5/48), respectively. The MLPA analysis showed that 38 cases possessed only 1 variant allele(RHD zygosity was Dd), while 10 cases possessed 2 variant alleles(RHD zygosity was DD). In Dd type individuals, point mutations were found in 18 cases and RHD/CE hybrid fusions were found in 20 cases. In DDindividuals, point mutations combined with RHD/CE hybrid fusions were found in 9 cases, deletion combined with RHD/CE hybrid fusions were found in 1 case. Variant alleles analysis basing on MLPA showed that 14 cases were weak D 15 and 22 cases were RhD VI type 3, however, the variant alleles were not identified in 7 cases due to lack of detecting probes and were identified via sequencing analysis. Two novel mutations, 79-81delCTC and 689G>A were also certificated by sequencing in 2 cases.

CONCLUSIONCcDee is the major Rh phenotype in RhD variants, weak D 15 and RhD VI type 3 are the main serologic type of RhD variants, point mutation and RHD/CE hybrid fusions are main molecular mechanism for RhD variant phenotype. Besides, 79-81delCTC and 689G>A are two novel alleles.