Volume 102 ·  Issue 42 ·  2022

Hospital-associated venous thromboembolism (HA-VTE) has become a public health problem that seriously affects the quality of medical care and patient safety. Many countries regarded VTE prevention as a key element of medical quality management, carried out quality improvement work in VTE prevention and achieved remarkable results. In China, there is also unremitting efforts and explorations in the field of VTE prevention and management. The national program for prevention and management of pulmonary embolism and deep vein thrombosis was officially launched. Through a series of measures such as excellent center construction, regional alliance, and strengthening of quality control and informatization, the national program has greatly promoted the construction of VTE prevention and management system in hospitals across the country. Strengthening the prevention and treatment of VTE has become the common will of the government, hospital administrators, clinical medical staff and the public. In the future, we need to continue to steadily promote the prevention and management of VTE, and comprehensively improve the quality control management level of VTE prevention and management in hospitals.

Venous thromboembolism (VTE) is an important cause of unexpected death in hospitalized patients and has posed a potential risk to the quality of care and patient safety. Quality evaluation and management is an important link in VTE prevention and treatment, is the key to promote the formation of long-term mechanism of VTE prevention and treatment, and is also an important way to promote clinical medical staff to carry out dynamic evaluation and implement prevention and treatment measures in a standardized and reasonable way. At present, there is still a lack of indexes to systematically evaluate the quality of VTE prevention and control in China. Based on this, the National Pulmonary Embolism and Deep Vein Thrombosis Prevention and Treatment Capacity Building Project Office organized an expert committee. On the basis of reviewing the guidelines, policies and standards issued at home and abroad, after Delphi expert consultation and multi-disciplinary expert discussion, three core indicators of evaluation quality, prevention quality and outcome quality were formulated based on the standards of "importance, specificity, representativeness, sensitivity and availability", and the names, definitions, calculation formulas, significance, data sources, evaluation methods, relevant explanations and recommendations of each quality indicator were clarified, in order to strengthen the attention and implementation of clinical medical staff on the dynamic assessment of VTE risk and bleeding risk and standardized prevention and treatment, and narrow the gap between clinical practice and evidence-based guidelines.

Type 2 inflammation is mainly mediated by Th2 cells, type 2 intrinsic lymphoid cells and related cytokines. Type 2 inflammatory diseases involve many fields, and there are many kinds of diseases, and it is common for multiple type 2 inflammatory diseases to coexist, which brings a heavy burden to patients. However, at present, basic and clinical research work on the pathogenesis of type 2 inflammation and related diseases There is still a gap in cross-domain cognition. In recent years, emerging targeted therapy has become an effective treatment for type 2 inflammatory diseases. This consensus describes the mechanism of type 2 inflammation and related diseases, and summarizes the clinical research results of targeted therapy for type 2 inflammatory diseases in recent years, hoping to provide a reference for clinicians to understand and treat type 2 inflammatory diseases.

To explore the relationship between germline rare variants of bromodomain and extraterminal domain (BET) protein family-encoding genes and susceptibility to cancer in some regions of China.

Capturing probes were designed for bromodomain-containing protein 2 (BRD2), BRD3 and BRD4 genes, and Illumina high-throughput sequencing platform was used to conduct targeted sequencing of genomic DNA of peripheral blood leukocytes from 1 673 patients with cancer and 1 661 individuals without cancer recruited between October 2015 and July 2018 from Chinese PLA General Hospital, the Second Affiliated Hospital of Guangxi Medical University, People′s Hospital of Macheng City, Hubei Province and Geneplus-Beijing Co. Ltd. Mutation detection and analysis were carried out according to the genome analysis toolkit (GATK) best practice guidelines, ANNOVAR and VEP software were used for annotation, and germline rare variants in BET family were screened. To determine potential pathogenic germline rare variants, clinical and experimental evidence was obtained from the ClinVar database and SIFT and Polyphen-2 softwares were used to predict pathogenicity. Fisher′s exact test was used to compare the difference of the carrying rate of variants in the case group and the control group, and multivariate regression analysis was performed with the SKAT software with sex and age used as covariates.

Among the 1 673 cancer patients, 911 were males and 762 were females, with the mean age was (57.9±11.7) years. There were 1, 111 cases (66.4%) of lung cancer, 266 cases (15.9%) of colorectal cancer, 186 cases of breast cancer (11.1%), and 110 cases (6.6%) of esophagus or gastric cancer. In the same period 1, 661 non-tumor control individuals were recruited, including 821 males and 840 females, with the mean age was (44.5±13.9) years. It was observed that there were 4 potential pathogenic germline rare variants in BRD2 gene carried by 17 patients with cancer, 5 potential pathogenic germline rare variants in BRD3 gene and 8 potential pathogenic germline rare variants in BRD4 gene. The carrying rate of potential pathogenic germline rare variants in BRD2 gene in cancer patients was 1.02% (17/1 673), significantly higher than that in controls without cancer [0 (0/1 661); OR=+∞, 95%CI: 4.81-+∞, P<0.001]. The carrying rate of potential pathogenic germline rare variants in BRD3 gene in cancer patients was 0.24% (4/1 673), and the difference was not statistically significant compared with controls without cancer [0.12% (2/1 661);OR=1.99, 95%CI: 0.46-10.47, P=0.690]. The carrying rate of potential pathogenic germline rare variants in BRD4 gene in cancer patients was 0.18% (3/1 673), and the difference was not statistically significant compared with controls without cancer [0.36% (6/1 661); OR=0.50, 95%CI: 0.14-2.08, P=0.340]. Furthermore, the dataset of whole exome sequencing of Chinese individuals in "Huabiao Project" was used as an additional control, and the rate of carrying BRD2 rare variants in cancer patients was 17/3 346 (0.51%), significantly higher than that in controls without cancer [0.07% (3/4 154); OR=7.07, 95%CI: 2.32-22.83, P<0.001]. Among the 17 patients carrying 4 potentially pathogenic germline rare variants of BRD2 gene, 9 were patients with lung cancer, 6 were patients with colorectal cancer, 1 was patient with breast cancer, and 1 was patients with esophagus or gastric cancer. The carrying rate of potential pathogenic germline rare variants in BRD2 gene in lung cancer patients was 0.81 (9/1 111), significantly higher than that in controls without cancer [0(0/1 661);OR=+∞, 95%CI: 3.95-+∞,P<0.001]. The carrying rate of potential pathogenic germline rare variants in BRD2 gene in patients with colorectal cancer was 2.26% (6/266), significantly higher than that in controls without cancer [0(0/1 661);OR=+∞, 95%CI: 9.03-+∞, P<0.001]. Wilcoxon rank-sum test results showed that patients with colorectal cancer carrying BRD2 rare variants had an earlier age at diagnosis [(47.0±7.4) vs (57.2±12.1) years old,P=0.017].

BRD2 gene may be served as a candidate genetic susceptibility gene for lung cancer and colorectal cancer. Carrying BRD2 potential pathogenic germline rare variants is associated with higher risk of lung cancer and colorectal cancer, and with earlier age of colorectal cancer.

To analyze the effects of Helicobacter pylori (H. pylori) infection and eradication therapy on small intestinal bacterial overgrowth (SIBO).

From September to December 2021, patients with abdominal symptoms who received ¹³C urea breath test at the Department of Gastroenterology in Peking University First Hospital were enrolled.¹³C urea breath test was used to detect H. pylori infection and patients were divided into H. pylori positive and negative groups accordingly. Lactulose hydrogen methane breath test was performed to determine SIBO. H. pylori positive patients were treated with quadruple therapy including amoxicillin, metronidazole, rabeprazole and bismuth potassium citrate. ¹³C urea breath test and lactulose hydrogen methane breath test were reexamined 6 weeks after the treatment.

A total of 102 patients (49 males and 53 females) were enrolled, with a mean age of (42.1±9.9) years. Among them, 49 patients were H. pylori negative and 53 were H. pylori positive. Moreover, 47 patients were SIBO positive and 55 were SIBO negative. There was no significant difference in age, sex, body mass index, abdominal symptoms and the diagnosis of chronic atrophic gastritis between H. pylori positive and negative patients at the enrollment (all P>0.05). The detection rate of SIBO inH. pylori infected patients was higher than that in uninfected patients, and the difference was statistically significant (60.4% vs 30.6%, P=0.003). Patients with SIBO had significantly more frequent abdominal distension (36.2% vs 10.9%, P=0.002) and constipation (27.7% vs 1.8%, P<0.001) than patients without SIBO. The rate of SIBO afterH. pylori eradication treatment was significantly lower than that before treatment (20.8% vs 60.4%, P<0.001). The remission rate of SIBO after eradication therapy was 66.7% (20/30). Besides, patients had obvious improvement of constipation (6.0% vs 18.9%,P=0.008), and the incidence of other abdominal symptoms decreased to various degrees including diarrhea, abdominal pain, abdominal distention and poor appetite.

H. pylori infection increases the risk of SIBO, and the quadruple regimen containing amoxicillin and metronidazole has a therapeutic effect for patients with H.pylori infection and concomitant SIBO.

To evaluate the short-term efficacy and safety of vedolizumab in patients with inflammatory bowel disease (IBD).

Patients with moderate and severe active IBD at the first use of vedolizumab from May 1 to October 31, 2021 were retrospectively enrolled. Then the clinical characteristics, and the efficacy and safety of vedolizumab were evaluated. Meanwhile, the clinical response rate, biological response rate and endoscopic response rate were calculated. Multivariate analysis was used to evaluate the independent influencing factors of short-term clinical efficacy and safety.

A total of 78 patients (44 males and 34 females) with IBD were enrolled, with a mean age of (40.5±11.9) years. The clinical remission rate, clinical response rate, biological remission rate, biological response rate and endoscopic remission rate was 60.3% (47/78), 85.9% (67/78), 70.5% (55/78), 43.6% (34/78) and 47.0% (31/66) respectively after 14 weeks of treatment. Body mass index (BMI) ≥ 18.5 kg/m² (HR=5.04, 95%CI: 1.50-16.91, P=0.009) and biological remission at 6 weeks of treatment (HR=15.22, 95%CI: 3.16-73.38, P=0.001) were predictors of endoscopic remission at 14 weeks of treatment. Adverse reactions occurred in 57 patients, with an incidence of 73.1%. The main manifestations were liver and kidney damage (37.2%) and infection (26.9%).

More than half of patients with moderate and severe active IBD can achieve clinical remission after 14 weeks of vedolizumab treatment. Baseline BMI level and biological remission at 6 weeks of treatment are predictors of mucosal healing at 14 weeks. The incidence of adverse reactions is not low, although serious adverse reactions are rare in short-term treatment.

To evaluate the quality of life and influencing factors of patients with herpes zoster (HZ) seen in hospitals.

Based on Zoster Brief Pain Inventory (ZBPI) and Five-level EuroQol Five-dimensional Questionnaire (EQ-5D-5L), a cross-sectional survey was conducted to evaluate the pain severity and quality of life of 332 HZ cases seen in 22 hospitals of Lu′an City (Anhui Province), Zibo City (Shandong Province) and Tongchuan City (Shaanxi Province) from October to December 2021. The censored least absolute deviations (CLAD) model was used to analyze the related factors affecting the changes of patients′ health utility values.

The 45.5% of 332 HZ cases were male. The median (Q₁,Q₃) age was 59 (50, 68) years. 59.64% of them assessed by ZBPI had moderate to severe pain in the past 24 hours (worst pain score≥5), and that of PHN cases was 84.8%(39/46). 77.7% (258/332), 77.4% (257/332) and 74.1% (246/332) of all patients reported that pain interfered with sleep, mood and general activities, respectively. Aging [β_40-49y (95%CI)=-0.11 (-0.15, -0.08); β_50-59y (95%CI)=-0.03 (-0.05, 0.00); β_60-69y (95%CI)=-0.09 (-0.12, -0.06); β_70-90y(95%CI)=-0.16 (-0.19, -0.12)], working status (unemployed) [β_farmer (95%CI)=0.15 (0.13, 0.18); β_retirees(95%CI)=0.21 (0.18, 0.24); β_employee (95%CI)=0.13 (0.10, 0.16) ], complications[β_PHN (95%CI)=-0.08 (-0.13, -0.04); β_{other complications} (95%CI)=-0.12 (-0.15, -0.08)], within 30 days after onset [β(95%CI)=-0.01 (-0.03, 0.01)] and treatment [β_{other complications} (95%CI)=-0.09 (-0.11, -0.06)] were related factors for the decline of health utility value (all P values <0.05).

More than half of the patients with HZ had moderate to severe pain in the past 24 hours, which had a serious negative impact on the physical and mental health of the patients. Elderly patients, acute patients and patients with complications had lower health utility values and worse health status. We suggest that eligible people be vaccinated with HZ vaccine as soon as possible.

A case of nephritic syndrome with abnormal renal function, splenomegaly and monoclonal immunoglobulinemia was reported in an elderly patient. Bone marrow examination considered that marginal region indolent small B cell lymphoma involved bone marrow. Positron emission computed tomography (PET-CT) indicated that the tumor originated from the spleen. The pathological diagnosis of splenectomy was splenic marginal region lymphoma (SMZL). Renal biopsy further confirmed the existence of lymphoma secondary to renal damage. The pathological manifestation was IgA nephropathy with tumor cell infiltration in renal interstitium. In the course of systemic chemotherapy for tumor, hematuria was reduced and renal function was improved. In this case, a complete chain of evidence was used to confirm the diagnosis of renal damage secondary to SMZL, which increased the clinician's experience in the diagnosis and treatment of renal disease secondary to hematological tumors.

Adenoid cystic carcinoma has a high degree of high-grade transformation and malignancy, poor postoperative prognosis and extremely high mortality. At present, Chinese clinicians have insufficient understanding of high-grade transformation of adenoid cystic carcinoma, and lack of effective treatment methods. Therefore, this article reviews the histopathology, clinical prognosis, pathogenesis, differential diagnosis and treatment of high-grade transformation of adenoid cystic carcinoma, so as to provide reference for practical clinical work.

Patients with early endometrial cancer had a better prognosis and a higher survival rate, but patients with advanced or recurrent endometrial cancer had a poorer prognosis, with an overall 5-year survival rate of less than 20%. There are no accepted consensus-based guidelines for the treatment of advanced or recurrent endometrial cancer, and there is an urgent clinical need to address this area. Adjuvant therapy for patients with endometrial cancer is performed by risk stratification based on histological parameters such as histological subtype and grade, lymphovascular space invasion and stage, however, these characteristics may be difficult to evaluate and even lack consensus among gynecologic pathologists. 4 molecular subpopulations of endometrial cancer: POLE (hypermutant), microsatellite instable (MSI) (hypermutant), high copy number (serous carcinoid), and low copy number group (endometrioid) groups. Different molecular types of endometrial carcinoma not only show obvious molecular and pathological features, but also have significant differences in clinical outcomes, but there are still some problems that need to be further solved. This article will introduce the latest research progress of molecular typing of endometrial cancer and its correlation with immunotherapy.

Lung cancer originates from the bronchial mucosa or glands of the lungs, and is a malignant tumor with the highest morbidity and mortality in China and even in the world. Non-small cell lung cancer (NSCLC) accounts for 85% of the total number of lung cancer cases and is a serious threat to people's health. While smoking is a major risk factor for lung cancer, genetic factors can also contribute to the development of lung cancer. In the past 20 years, genome-wide association studies (GWASs) have strongly linked 45 genetic loci to NSCLC. However, most studies have been conducted in European populations. Recent studies have found another six NSCLC loci in the Chinese population, but there is still a lack of a high-quality reference dataset for the Chinese population. In addition, traditional GWASs mainly studies common and low-frequency variants by attributing gene arrays with haplotype references. Although this method can study more than 90% of common variants, it is difficult to use to study rare variants. In order to provide a high-quality reference dataset for lung cancer research in China, improve the efficiency of array-based genetic research, and reveal the possible genetic causes of lung cancer on a larger scale, this study performed large-scale whole genome sequencing on 2 984 NSCLC patients and 3 020 non-cancer control patients from the Nanjing lung cancer cohort. As a result, 91 942 226 (91.43%) single nucleotide variants (SNVs) and 8 623 324 (8.57%) indels (indels) of 50 bp or less were found. Of these, only 8 079 426 SNVs (8.79%) and 1 082 986 indels (12.56%) were considered common and low-frequency [minor allele frequency (MAF) ≥0.5%], and 20 common and low-frequency loci (MAF ≥0.5%) were identified, including five newly reported loci, SRC, DSP, RGL2, BTN3A2, and CCDC116. For rare variants with loss of function (MAF<0.5%), the study found that BRCA2 and 18 other cancer susceptibility genes affected 5.29% of NSCLC individuals, and 98.91% (181/183) of newly identified loss-of-function variants were associated with NSCLC risk. These association study findings were validated in an independent case-control study including 4 410 individuals and a prospective cohort study including 23 826 individuals.

Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome characterized by germline pathogenic variants in mismatch repair (MMR) -related genes that cause microsatellite instability. Patients who meet the clinical criteria for LS and MMR deficiencies and do not have any identified germline pathogenic variants are generally considered to have Lynch-like syndrome (LLS). These patients are at higher risk of colorectal cancer and extracolonic tumors, but there are limited studies on their underlying genetic etiology. Recent studies have found that there is a biallelic germline variation of the MUTYH gene in LLS cases, and MUTYH-associated polyposis can overlap with the LS phenotype through somatic inactivation of the MMR gene. In addition to this, LLS patients carrying POLE and POLD1 germline variants have also been identified. Germline variants in DNA repair genes, such as MCM8, MCM9, WRN, MCPH1, BARD1, REV3L, EXO1, POLD1, Rfc1, RPA1, and MLH3, have also been reported in patients with LLS, but the results of the potential germline mutation profile of LLS in the Brazilian population are unknown. The study included 20 patients with LLS diagnosed from the Barretus Cancer Hospital in Brazil and performed whole exome sequencing (WES). It was found that among these 20 patients, 60% were female patients, and the age at which the tumor was first diagnosed was (48±8) years old. 75% of patients (n=15) with colorectal cancer as the first tumor, followed by endometrial cancer (n=2), ovarian cancer (n=2) and gastric cancer (n=1）。 Five patients were diagnosed with a second type of tumor; These tumors include colorectal cancer, endometrial cancer, breast cancer, and non-melanoma. A total of 90% of patients had a family history of cancer and 75% had LS-associated tumors in their families. In addition, 319 high-quality germline variants were screened in 2 389 gene analyses. Variants were classified according to the American Society for Medical Genetics and Genomics (ACMG) criteria, of which, 33.5% of the variants were classified as benign or probably benign (107/319), 63.9% of the variants were of uncertain significance (204/319), and 2.5% of the variants were classified as pathogenic or probably pathogenic (8/319). Among the known cancer genes MUTYH and ATM, pathogenic or likely pathogenic variants were found in 35% (7/20) of patients. These patients carrying the pathogenic variant compared with those who did not carry the pathogenic variant at the age at which the tumor was first diagnosed [mean age 48.3 vs 48.2 years,P=0.974], number of tumor families (mean number of tumors 3.7 vs 6.7,P=0.193), tumor grade (P=0.650) or tumor stage (P=0.854) None of the differences were statistically significant. In addition, rare potentially pathogenic variants have also been identified in the DNA repair gene POLN and other cancer-related genes PPARG, CTC1, DCC, and ALPK1.