Volume 102 ·  Issue 24 ·  2022

Chinese expert consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis (HLH) associated with lymphoma was revised on the basis of evidence-based medical evidence in combination with domestic and international research progress. It added the classification of "according to the difference in the causes of HLH". For the first time, the revised version included the classification of lymphoma-associated HLH induced by immunotherapy. The contents of genetic background defects and central nervous system involvement in lymphoma-associated HLH were also supplemented. This article gives a detailed interpretation of the updated content in the consensus.

In recent years, with the rapid development of interventional pulmonary diseases, new instruments and new concepts are constantly updated. The increased detection rate of pulmonary nodules increases the demand of patients. These factors jointly promote the continuous progress of bronchoscopy diagnosis and treatment technology. The following techniques including thin/ultrathin bronchoscopes, radial probe endobronchial ultrasound (R-EBUS), and navigation bronchoscopy including virtual navigation bronchoscopy (VNB) and electromagnetic navigation bronchoscopy (ENB), robotic-assisted bronchoscopy (RAB), frozen biopsy for the diagnosis of diffuse lung diseases are particularly prominent and important in clinical practice. This paper reviews the progress and application of bronchoscopy in interventional diagnosis through the review of literature published in 2021.

Based on the clinical evidence obtained during the past decade, we reviewed herein the evidences in the treatment of 5 types of common pleural diseases. (1) Therapeutic pleural interventions are not recommended for patients with malignant pleural effusion (MPE) who are asymptomatic. In patients with symptomatic MPE, large-volume thoracentesis should be performed in MPE patients to figure out if the patient′s symptoms are related to the effusion and/or if the lung is expandable; if so, indwelling pleural catheters and/or talc pleurodesis can be used as first-line definitive intervention. Indwelling pleural catheters, but not pleurodesis should be used in those with symptomatic MPE with nonexpandable lung, failed pleurodesis, or loculated effusion. (2) Randomized controlled trials concerning tuberculous pleurisy management are always scarce. Based on the data from pulmonary tuberculosis trials, it can be accepted that anti-tuberculosis treatment regimen for tuberculous pleurisy with isoniazid, rifampin, and pyrazinamide for two months followed by four months of two drugs, isoniazid and rifampin. (3) A combination of tissue plasminogen activator and deoxyribonuclease can be instilled intrapleurally as the initial treatment, or as a follow-up treatment after surgery for pleural infection. The recommended dosages are as follows: tissue plasminogen activator 10 mg, twice a day, deoxyribonuclease 5 mg, twice a day. (4) The randomized controlled trial has provided evidence that conservative management is an acceptable alternative to interventional management for moderate-to-large primary spontaneous pneumothorax. (5) For patients with malignant pleural mesothelioma, nivolumab plus ipilimumab is capable of significantly improving the overall survival of patients versus platinum plus pemetrexed chemotherapy, supporting the use of this regimen as the first-line treatment for these patients, regardless of histological subtype.

In the past, acute hepatitis of unknown etiology in children was sporadic. However, during the last three weeks, there has been a trend of short-term outbreak around the world. As of May 3, 2022, at least 228 cases had been reported in about 20 countries and regions. The main clinical manifestations of the children included abdominal pain, diarrhea, vomiting, jaundice, and hepatomegaly. The liver functions including alanine aminotransferase and total bilirubin increased sharply. About 8.8% of the children needed liver transplantation. The etiology is not clear, but adenovirus type 41 is currently considered to be the most likely cause. Clinicians should keep alert to acute hepatitis of unknown etiology in children, strengthen epidemic surveillance, clinical treatment, and carry out necessary health education.

Hemophagocytic syndrome is a critical disease in which cytotoxic T cells and natural killer cells are over-activated due to various triggers, and stimulate monophagy system and secrete large amounts of inflammatory cytokines. Lymphoma is one of the important causes of secondary hemophagocytic syndrome. In recent years, with the deepening of understanding of diseases, the improvement of detection methods and the advent of new drugs, the diagnosis and treatment system of lymphoma-related hemophagocytic syndrome has gradually improved. In order to better guide the clinical practice of Chinese doctors, the Lymphoma Professional Committee of Chinese Anti-Cancer Association, the Lymphocyte Disease Group of Hematology Branch of Chinese Medical Association and the Chinese Hemophagocytic Syndrome Expert Alliance, based on the 2018 edition of the Chinese Expert Consensus on Diagnosis and Treatment of Lymphoma-related Hemophagocytic Syndrome, combined with new progress, revised the classification and treatment of diseases, and increased the interpretation of central nervous system involvement, aiming at standardizing and improving the diagnosis and treatment of lymphoma-related hemophagocytic syndrome in China.

Renal anemia is a common and important complication in patients with chronic kidney disease (CKD). At present, the main therapeutic drugs for renal anemia are erythropoietin stimulator (ESA) and iron, but they still can't fully meet the clinical needs. Hypoxia-inducible factor (HIF) is a nuclear factor that regulates the imbalance of oxygen homeostasis. Regulation of HIF pathway by using HIF prolyl hydroxylase inhibitor (HIF-PHI) has become a new strategy for the treatment of renal anemia. China took the lead in completing the world's first phase III clinical trial of the HIF-PHI drug roxastat in the treatment of renal anemia in the world, and was first approved for marketing application in 2018, gaining rich clinical application experience. In order to summarize clinical experience in time, better guide the clinical use of roxastat, and improve the treatment effect of anemia in patients with CKD, the Nephrology Professional Committee of the Chinese Society of Research Hospitals organized experts in the renal field in my country to jointly formulate the Chinese Expert Consensus on the Treatment of Renal Anemia with Roxastat.

With the inclusion of immune checkpoint inhibitors as anti-tumor drugs in medical insurance in China, a large number of cancer patients have benefited from them, but the emergence of immune checkpoint inhibitor-related toxicities has led to an increase in unexpected mortality of cancer patients and reduced the survival time of patients. This proposal combines domestic and foreign literature, domestic and foreign drug instructions, published guidelines and experts' clinical practice experience, focuses on the two main lines of "prevention" and "management", runs through the whole process of "prevention-evaluation-diagnosis-treatment-follow-up" of immune checkpoint inhibitor-related toxicity, and focuses on "early detection, early diagnosis and early treatment", so as to provide clinicians and hospital administrators with practical suggestions that can effectively improve the level of prevention and treatment of immune checkpoint inhibitor-related toxicity and improve patient medication safety, so as to further promote the homogenization of prevention and management in various regions. This recommendation includes an overview of immune checkpoint inhibitor-related toxicity, risk assessment, monitoring, follow-up recommendations, and also describes recommendations for early identification and management of immune-related adverse events, hoping to provide clinical practice reference for clinicians and managers.

To evaluate tourniquet effect on the morphology and stiffness of quadriceps in patients receiving total knee arthroplasty (TKA).

Total of 80 patients with primary knee osteoarthritis receiving unilateral primary TKA from August 2020 to June 2021 in Peking University Third Hospital were enrolled in this randomized controlled trial. The patients were randomly divided into tourniquet group and non-tourniquet group (40 cases in each group). The study measured and compared postoperative thickness and stiffness of quadriceps, as well as circumference of the affected thigh in two groups.

There were 11 males and 29 females in tourniquet group, 9 males and 31 females in non-tourniquet group, with mean age of (69.1±5.1) years and (67.4±5.3) years, respectively. There was no significant difference in demographic information such as gender, age and BMI (all P<0.05). Postoperative thickness of quadriceps, stiffness of quadriceps and circumference［x¯±s or M （Q₁，Q₃）］of the affected thigh in all patients were (2.76±0.69) cm, 25.20 (17.83, 32.90) m/s, 54.00 (51.13, 56.00) cm. These outcomes in tourniquet and non-tourniquet group［x¯±s or M （Q₁，Q₃）］were (2.78±0.76) cm and (2.73±0.61) cm, 24.00 (17.15, 33.13) m/s and 25.20 (18.68, 32.85) m/s, 54.00 (49.75, 55.00) cm and 54.50 (52.13, 57.53) cm, respectively; no significant deference was found in these indexes between the two groups (all P>0.05).

Tourniquet has no significant effect on morphology and stiffness of quadriceps in patients undergoing TKA.

To discuss the clinical value of preserving subvalvular structure in mitral and aortic valve replacement surgery and its effect on left ventricular contractility.

A total of 97 patients who underwent mitral valve replacement surgery in the Adult Cardiac Surgery of Heart Center of Henan Provincial People′s Hospital, Central China Fuwai Hospital from June 2016 to December 2018 were selected as the research subjects, of whom 45 cases were preserved subvalvular structure and 52 cases were in the total resection group (intraoperative total resection of the mitral valve and subvalvular chordae tendineae). General cardiac function indexes and left ventricular function quantitative indexes were compared before and in 3 months and 6 months after the operation of the two groups; The changes of the overall longitudinal strain of the long axis of the apex and the overall circumferential strain of the short axis of the left ventricle determined by the two-dimensional speckle tracking technology were compared before and after the operation.

The ages of the patients in the preservation group and the total resection group were (41.8±11.3) and (43.3±10.6) years old, respectively, and the male proportions were 58.0% (26 cases) and 44.0% (23 cases), respectively, with no significant difference (all P>0.05). The aortic occlusion time and cardiopulmonary bypass time of the patients in the preservation group were (57.8±4.5) and (78.6±6.7) min, respectively, which were longer than those in the total resection group [(48.1±4.4) and (48.1±4.4) min, respectively] (all P<0.05). The left atrial pressure of the patients in the preservation group at shutdown was (8.4±1.8) mmHg (1 mmHg=0.133 kPa), which was lower than that of the total resection group (11.3±2.5) mmHg (P<0.001). There were interaction effects between groups and time in regards to the left ventricular end-diastolic diameter ( LVEDD ), left ventricular ejection fraction ( LVEF ) and Tei index, as well as the strain rate of mitral annulus and left ventricular wall of interventricular septum of the preservation group and the total resection group (all P<0.05). LVEDD and LVEF of patients in the preservation group at 3rd month after operation were (44.7±4.0) mm and (45.5±4.2) mm, and at 6th months were (56.5±4.9)% and (58.8±5.0)%, respectively, all larger than (42.7±3.6) mm and (42.7±3.6) mm, (54.5±4.6)% and (56.3±4.8)% of the total resection group. The measured value of LVESD in the preservation group at 3rd month after surgery was (32.6±3.2) mm, which was greater than that in the total resection group (31.2±3.4) mm (P<0.05). The Tei index of patients in the preservation group at 3rd and 6th months after surgery were 1.0±0.2 and 0.8±0.2, respectively, which were lower than those in the total resection group 1.2±0.3 and 0.9±0.2 (all P<0.05).

Preserving the subvalvular structure during mitral valve replacement surgery can better improve the patient′s left ventricular function and left ventricular systolic capacity.

To evaluate the effect of "Smoking cessation: Doctor first" program on smoking medical staff.

From December 2016 to September 2019, 1 747 smoking medical staff from 54 units of China Tobacco Cessation Alliance were enrolled into "Smoking cessation: Doctor first" program. Demographic characteristics, smoking characteristics, degree of tobacco dependence, willingness to quit smoking and other related factors were collected during the baseline survey. Multivariate logistic regression model was used to analyze the related factors of willingness to quit. The subjects were given intensive smoking cessation intervention from October 2017 to September 2019, including education on the hazards of smoking, methods of smoking cessation and giving smoking cessation drugs. After intervention, the subjects were investigated about their smoking cessation progress and the effect of the project was evaluated.

The subjects were (41±11) years old, 91.9% (1 609/1 747) were male and 62.2% (1 086/1 747) were daily smokers. The main reasons for smoking included the influence of friends [697 (39.9%)], the need for social entertainment [629 (36.0%)], the relief of mental stress [589 (33.7%)] and the refreshment [459 (26.3%)]. At baseline, 52.9% (885/1 672) and 43.2% (755/1 747) smokers had intention to quit smoking and had planned to quit within one year, respectively. Multivariate logistic regression model analysis showed that: low education level [OR (95%CI) of high school and junior high school and below were 2.42 (1.61, 3.63) and 1.57 (1.18, 2.11)], daily smoking [OR (95%CI): 1.38 (1.06, 1.78)], thinking quitting smoking was not important [OR (95%CI): 4.15 (3.33, 5.18)] and having no quitting experience [OR (95%CI): 3.21 (2.53, 4.05)] were associated with no intention to quit smoking. After intensive smoking cessation intervention, 81.0% (1 415/1 747) smokers started to quit and 36.6% (518/1 415) quit smoking with drugs, both higher than the baseline level (all P values<0.001). By the end of the program, 60.2% (852/1 415) of the medical staff had quit smoking successfully.

"Smoking cessation: Doctor first" program can improve the willingness to quit and the proportion of using smoking cessation drugs of medical staff.

A 64-year-old female patient with pyloric adenoma (PGA) of the stomach body is reported. It is a rare sporadic case, and the patient has no autoimmune gastritis, no history of familial adenomatous polyps, no Helicobacter pylori infection and no atrophic gastritis. PGA is a rare gastrointestinal tumor. The glands presented gastric pyloric differentiation, the cells were cubic or columnar, the cytoplasm was eosinophilic to hermaphilic, and there was no mucin cap. Immunohistochemically stained cells had markers of gastric pyloric gland differentiation, including mucin 5Ac (MUC5Ac) and MUC6. The patient underwent endoscopic submucosal dissection (ESD) under intravenous anesthesia on 19 Jan 2018. Final pathological diagnosis: gastric PGA; Macroscopic classification: 0~ IIA; extent of lesion : 1.0 cm x 0.5 cm; Horizontal margin and basal margin net. PGA can be treated conservatively or completely resected by ESD.

Although androgen deprivation therapy has some effect on the treatment of progressive and metastatic prostate cancer, patients inevitably develop drug resistance and develop castration-resistant prostate cancer (CRPC). Among them, reactivation of the androgen receptor (AR) signaling pathway is a key driver of CRPC progression. In recent years, proteolytic targeting chimeras (PROTACs) have developed rapidly in the field of CRPC by forming ternary complexes with target proteins and E3 ubiquitinated ligases to efficiently and specifically degrade target proteins. Among them, ARV-110, ARV-471 and AR-LDD have all entered the clinical trial stage. However, PROTACs molecules face many difficulties in the research process. With the development of nanomedicine, its combined application with PROTACs may play an important role in reducing the expression of AR in CRPC patients and solving the disease progression. This article reviews the treatment of AR and CRPC, the mechanism and characteristics of PROTACs, the application and existing problems of PROTACs in the research field of castration-resistant prostate cancer.

Epstein-Barr virus (EBV) -positive diffuse large B-cell lymphoma unspecified type (EBV⁺DLBCL-NOS) is a rare disease that was first reported in 2003 and was temporarily designated as elderly EBV in the 2008 World Health Organization (WHO) classification⁺DLBCL, officially named EBV in the 2016 WHO classification⁺DLBCL-NOS. Its incidence was slightly higher in Asian and Latin American countries (4.7% to 28.0%) than in Western countries (4.4% to 5.8%). With EBV^-DLBCL compared to EBV⁺Whether DLBCL has a worse prognosis is reported differently by different studies, which may be related to the age, geography and small RNA encoded by Epstein-Barr virus (EBER) of the included patients⁺The proportion of tumor cells is different. The 2016 WHO criteria stipulated that the positive rate of EBER was>80%, and this study was the largest retrospective cohort study meeting this diagnostic criteria. 70 cases of EBV were included in 1 696 patients with DLBCL-NOS diagnosed at the University Hospital of Lyon-Sud, France, from 2006 to 2019⁺DLBCL-NOS patients (prevalence 4.1%). The median age at diagnosis was 68.5 years; 79% of the patients were in advanced stage (stage Ⅲ-Ⅳ), 48% had extranodal lesions, and 14% had hemophagocytic lymphohistiocytosis (HLH) (8 cases at diagnosis and 1 case during treatment). The histopathology showed pleomorphism in 46 cases and monomorphism in 21 cases; All were non-germinal center B cell phenotypes, and most tumor cells expressed CD30 and programmed death ligand 1 (98% and 95%, respectively). The latent type of EBV infection, 88% were type Ⅱ, 12% were type Ⅲ. In terms of treatment, 59% of the patients received immunochemotherapy, 22% received chemotherapy, and 19% received only palliative care due to advanced age and poor physical condition. At a median follow-up of 48 months, 5-year progression-free survival and overall survival were 52.7% and 54.8%, respectively. Older age (>50 years) and combined HLH were associated with shorter progression-free and overall survival in multivariate analyses. Further comparison of 56 cases of EBV receiving standard therapy (immunochemotherapy or chemotherapy)⁺DLBCL-NOS patients and 425 cases of EBV^-progression-free survival and overall survival in DLBCL-NOS patients, and in younger patients, the effect of EBV status on their progression-free survival and overall survival was not statistically significant (5-year progression-free survival: EBV⁺Than EBV^-91.3% vs. 69.0% of patients,P=0.066； 5-year overall survival: EBV⁺Than EBV^-91.3% vs. 83.8% of patients,P=0.438）； However, in patients>50 years of age, there was no statistically significant difference in 5-year progression-free survival between the two groups (47.9% vs. 45.8%,P=0.405), EBV⁺The 5-year overall survival rate of patients was lower (53.0% vs. 60.8%,P=0.038）。

Smoking cessation drugs can effectively relieve withdrawal symptoms and help smokers who are willing to quit smoking to improve the success rate of quitting smoking. Varenicline and nicotine patch are two first-line smoking cessation treatments proven effective by evidence-based medicine. At present, the guidelines routinely recommend the use of varenicline and nicotine patches separately. Regarding whether the combined use of the two drugs and prolonged treatment time are beneficial to improving the smoking cessation rate, the current research data are limited and the conclusions are inconsistent. Therefore, the researchers conducted a clinical trial to compare the efficacy of varenicline alone versus in combination with nicotine patches, and the standard course of treatment (12 weeks) versus the extended course of treatment (24 weeks).

Tobacco dependence is a major obstacle to successful smoking cessation, and its essence is a fatal chronic disease with lesions in the brain. However, the epidemiological characteristics of tobacco dependence in China are poorly known at present, and the prevalence of tobacco dependence (including whole population and specific population) and the prevalence characteristics of tobacco dependence are unknown. Therefore, the researchers carried out a nationally representative epidemiological study, and analyzed the epidemic situation of tobacco dependence in China through the "2018 National Residents' Health Literacy Surveillance Survey". The survey used a stratified multi-stage random sampling method and included 84,839 subjects aged between 20 and 69 years from 31 provinces, municipalities and autonomous regions in China. The diagnostic criteria for tobacco dependence are based on international standards (ICD-10, DSM-4) and the Chinese Clinical Guidelines for Smoking Quitting (2015 Edition). The results showed that the smoking rate in China is about 25.1%, among which men are significantly higher than women (47.6% vs 1.9%), and there are differences in smoking rates in different provinces (12.9% ~37.9%). In the whole population, the prevalence of tobacco dependence was approximately 13.1% (95%CI：12.2%~14.1%）； Among current smokers, the prevalence of tobacco dependence is about 49.7% (95%CI: 46.5% to 52.9%), and the difference between men and women was not statistically significant (49.7% vs 50.8%). The disease risk of tobacco dependence is associated with smoking behavior, including the number of smoking pack years [OR（95%CI): 1.62 (1.54~1.70)], number of cigarettes smoked per day [OR（95%CI): 2.01 (1.78 to 2.27)] and smoking onset age [OR（95%CI）：0.93（0.90~0.97）］。 In addition, smokers with tobacco dependence were less likely to successfully quit [OR（95%CI）：2.88（2.59~3.21）］。 Based on this, it is estimated that about 183.5 million (170.4 million to 197.4 million) smokers in China suffered from tobacco dependence in 2018, of which 177.5 million were men.

Worldwide, there were about 2.09 million new cases of lung cancer and about 1.76 million deaths in 2018, ranking first among malignant tumors. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases, and smoking is an important risk factor for it. Studies have shown that more than 80% of NSCLC patients have a history of smoking, and about 40% to 50% of NSCLC patients are still smoking at the time of diagnosis. At present, there is limited research evidence on whether smoking cessation after diagnosis of lung cancer can improve the survival rate of lung cancer patients, and it is not clear whether there is a difference in smoking cessation effect between mild to moderate smokers and heavy smokers, as well as early and advanced cancer patients. Therefore, the investigator conducted a prospective study to enroll and follow-up patients with non-small cell lung cancer (NSCLC) to assess whether smoking cessation after lung cancer diagnosis has an impact on disease progression and the risk of death. The study enrolled 517 smokers diagnosed with early NSCLC between 2007 and 2016 and followed up until 2020. Primary outcome measures were overall survival, progression-free survival, lung cancer-related mortality, all-cause and cancer-specific mortality.HR。 The results showed that 220 (42.5%) quit smoking and 297 (57.4%) continued to smoke during a mean follow-up period of 7 years. The mean survival of patients was 5.2 years, with a total of 327 (63.2%) deaths, 273 (52.8%) cancer-specific deaths, and 172 (33.7%) disease progression (local recurrence or metastasis). The adjusted median survival time of those who quit smoking was 21.6 months longer than that of those who continued smoking (6.6, 4.8,P=0.001）。 And the 5-year overall survival rate was higher in the smoking cessation group than in the continuing smoking group (60.6% vs 48.6%,P=0.001), with higher progression-free survival (54.4% vs. 43.8%,P=0.004）。 When adjusted, smoking cessation significantly reduced all-cause mortality [HR（95%CI): 0.67 (0.53-0.85)], cancer-specific mortality [HR（95%CI): 0.75 (0.58 to 0.98)] and risk of disease progression [HR（95%CI）：0.70（0.56~0.89）］。 Similar results were obtained in subgroup analyses of mild, moderate and heavy smokers and patients with early and advanced cancer.