Epidemical characteristics of human brucellosis in Inner Mongolia Autonomous Region from 2018 to 2020 / 中华地方病学杂志

Objective:To investigate the epidemic characteristics of human brucellosis in Inner Mongolia Autonomous Region from 2018 to 2020, and provide a reliable scientific basis for formulating brucellosis prevention and control strategies in Inner Mongolia Autonomous Region.Methods:A retrospective study was carried out to collect data of human brucellosis in Inner Mongolia Autonomous Region from 2018 to 2020 from the "China Disease Control and Prevention Information System", and the monitoring data and information of confirmed cases were collected from the annual summary data reported by the leagues (cities) of the Inner Mongolia Autonomous Region. Using descriptive epidemiological methods, the epidemic situation, three distributions (time, region and population distributions) of brucellosis, and the serological and pathogenic test results of active monitoring population were analyzed.Results:From 2018 to 2020, a total of 40 665 cases of brucellosis were reported in Inner Mongolia Autonomous Region, with an annual average incidence rate of 53.47/100 000. The number of annual incidence had increased from 10 111 in 2018 to 16 406 in 2020, and the annual incidence rate had increased from 39.99/100 000 in 2018 to 64.60/100 000 in 2020. The spring and summer was the peak incidence, mainly in March to August, accounting for 64.90% (26 390/40 665) . There were reports of brucellosis cases in 12 leagues (cities) of Inner Mongolia Autonomous Region, and the top 3 regions with the number of reported cases were Tongliao City (9 896 cases), Xing'an League (6 136 cases) and Chifeng City (4 934 cases). The age of onset of brucellosis cases was mainly 30 - < 65 years old(33 539 cases), and the sex ratio between men and women was 2.18 ∶ 1.00 (27 890 ∶ 12 775); the occupational distribution was mainly farmers, accounting for 79.23% (32 221/40 665). From 2018 to 2020, 704 085 people were actively monitored in the region, of which 391 941 were serologically tested, and the infection rate was 4.57% (17 920/391 941); and there were 9 539 new cases in the active monitoring population. In 3 years, 19 strains of Brucella sheep type 3 and 11 strains of Brucella sheep type 1 were isolated. Conclusions:From 2018 to 2020, the incidence rate of brucellosis in Inner Mongolia Autonomous Region is increasing year by year. There are many new cases in the active monitoring population, and more underreporting cases. It is recommended to expand the scope of monitoring, strengthen pathogen monitoring among humans and animals, and joint prevention and control of various departments to improve the self-protection awareness of the masses.

Clinical characteristics of eight cases of immune checkpoint inhibitor-related colitis / 中华消化杂志

Objective:Summarize and analyze the clinical features of immune checkpoint inhibitor (ICI)-related colitis.Methods:From January 2019 to September 2020, the clinical data of 8 patients with ICI-related colitis from Peking Union Medical College Hospital were retrospectively collected and including the onset of ICI-related colitis, clinical symptoms, endoscopic and pathological findings, treatment, comorbidities and resuming of ICI. Independent sample t test was used for statistical analysis. Results:Eight patients were all male, and the median age (range) was 66 years old (55 to 74 years old), 7 cases were diagnosed with stage Ⅳ lung cancer and 1 case was diagnosed with stage Ⅲc pyelo-carcinoma. Among 8 patients, 4 cases of ICI-related colitis occurred during combination of anti-programmed death-1 (PD-1) treatment and chemotherapy, 2 cases occurred during anti-PD-1 monotherapy after combination of anti-PD-1 treatment and chemotherapy, and 2 cases occurred after anti-PD-1 monotherapy. The median time (range) was 44 d (27 to 128 d) from initial anti-PD-1 treatment to the onset of ICI-related colitis and the median time (range) was 8 d (6 to 35 d) from last anti-PD-1 treatment to onset of ICI-related colitis. The ICI efficacy of 4 patients had partial response, 2 patients had stable disease, 1 patient had disease progression, and 1 patient′s condition was not assessed. All 8 patients had moderate to severe extensive colitis. The main clinical manifestation was diarrhea (5/8), 3 patients accompanied by abdominal pain. The endoscopic findings were diffuse mucosal erosion, accompanied by ulcer in 2 patients. The main pathologic findings were cryptitis or crypt abscess, accompanied by apoptosis in 2 patients. Eight patients were all treated with glucocorticoids, among them 2 patients were further treated with biologics, due to the insufficient efficacy of glucocorticoid treatment, 4 patients had opportunistic infections. The initial prednisone dose for patients with opportunistic infections and patients without opportunistic infections was (85.00±52.60) and (60.00±23.09) mg, respectively. The prednisone treatment course was (8.75±4.03) and (7.50±3.11) weeks, respectively, and the differences were not statistically significant (both P>0.05). The colitis relapsed in all 3 patients after resuming of ICI. Conclusions:ICI-related colitis had corresponding ICI treatment history and clinical, endoscopic, and histopathological features. Glucocorticoid is the main treatment, and it is prone to relapse after resuming of ICI.

Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE).@*METHODS@#This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE.@*RESULTS@#This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively.@*CONCLUSIONS@#Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Clinical Diagnosis and Treatment Recommendations for Immune Checkpoint Inhibitor-related Hematological Adverse Events / 中国肺癌杂志

Immune checkpoint inhibitors are able to reactivate the immune system therefore enhance the anti-tumor effects. However, over-activated T cells may induce immune related adverse events (irAEs). Hematological irAEs are rarely reported, which mainly represent as mono-lineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even lethal, such as hemophagocytic lymphohistiocytosis. The clinical manifestations of hematological irAEs will be summarized and recommendations of diagnosis and treatment are proposed.

Management of Rheumatic Adverse Events Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) have made remarkable breakthroughs in cancer treatment. However, the widely use of ICIs is associated with a spectrum of immune-related adverse events (irAEs). These adverse events can affect any organ system. In this article, we have made a systemic review about the clinical characteristics of rheumatic irAEs, and also summarized irAEs in patients with pre-exsiting rheumatic disease. We also focus on the management of rheumatic irAEs.

Recommendation of Diagnosis and Management for the Infections Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) have been widely used in management of malignant tumor. Programmed death ligand 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have been introduced to treat non-small cell lung cancer (NSCLC) in recent years. Currently, PD-1/PD-L1 inhibitors are considered to have minor side effects and do not independently increase the risk of infection. However, they may cause immune-related adverse events (irAEs) that can require immunosuppressive therapy with corticosteroids and/or immunosuppressants, leading to opportunistic infections. Furthermore, there were reports about reactivation of chronic/latent infections without irAEs. Thus, immune checkpoint inhibitor related infections have drawn more and more attention in the world. In this paper, we described the potential mechanism, available clinical data and recommendation of diagnosis and management for PD-1/PD-L1 inhibitor related infections.

Clinical Diagnosis and Treatment of Immune-related Adverse Events in Digestive System Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

Immunotherapy for malignant tumors is a hot spot in current research and treatment of cancer. The activation of programmed cell death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA)-4 relevant signaling pathway can inhibit the activation of T lymphocytes. Tumor cells can achieve immune escape by activating this signaling pathway. By inhibiting this signaling pathway, immune-checkpoint inhibitors (ICIs) activate T lymphocytes to clear the tumor cells. Therefore, the adverse effects of ICIs are mainly immune-related adverse events (irAEs). The digestive system, including gastrointestinal tract and liver are vital organs of digestion and absorption, metabolism and detoxification, as well as important immune related organs, which are the commonly affected system of irAEs. This review separately explains the incidence, clinical features, diagnosis and treatment of liver and gastrointestinal adverse events in ICIs.

Clinical Diagnosis and Treatment Recommendations for Ocular Toxicities of Target Therapy and Immune Checkpoint Inhibitor Therapy / 中国肺癌杂志

The increasing use of target therapy and immunocheckpoint inhibitors in cancers has brought new hope of survival to patients with advanced tumors. However, more and more adverse side-effects and toxicities of these medications had been reported, affect almost all human organs including the eye. These adverse effects may affect the entire ocular tissues, like eyelid, eye lashes, conjunctiva, cornea, uvea, retina, optic nerve and so on, which are always been ignored by patients and doctors. In this paper we will summarize the characteristics of the related ocular diseases and give our advice on how to diagnose and manage these diseases.

Clinical Diagnosis and Treatment of Immune-related Adverse Events of Edocrine System Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

As a new type of anti-cancer drugs, immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic effects in many malignant tumors. By virtue of their targets and mechanisms of action, ICIs can cause autoimmune and inflammatory effects, termed immune-related adverse events (irAEs). Unlike traditional therapies, irAEs are latent and unstable. Severe adverse reactions will force patients to discontinue treatment and even affect their survival. Therefore, with the wide application of ICIs in clinical practice, clinicians need to fully understand the possible adverse reactions of such drugs and appropriate treatment strategies, in order to improve the survival rate and treatment effect of patients receiving ICIs. In this article, we review the incidence, clinical features, diagnosis and treatment of immune-related endocrine events that may occur with administration of ICIs.

Clinical Diagnosis and Treatment Recommendation of Immune-related Adverse Renal Events Related to Immune Checkpoint Inhibitor / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) have been used more and more Increasingly in clinical oncology treatment, which has significantly improved the prognosis of cancer patients. Over-activation of T cells and related signaling pathways may cause immune-related adverse effects. Renal immune side-effects are relatively rare, but some of them are serious and fatal. This review analyses of the Incidence, clinical and pathological manifestations of ICIs-induced renal injury, and focuses on the differential diagnosis and treatment. Because there are many secondary factors that need to be differentiated from immune mechanism, renal biopsy should be performed if necessary to determine the important decision.

Management of Dermatologic Toxicities Related to Immune Checkpoint Inhibitors / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) represent a major breakthrough in cancer therapy. Immune-related adverse events (irAEs) may occur during treatment due to their unique mechanism of action. Dermatologic toxicities appear to be one of the most prevalent irAEs. The most common symptoms are maculopapular rash and pruritus. Serious dermatologic AEs, including Stevens-Johnson syndrome and toxic epidermal necrolysis, are rare. In this review, we summarized guidelines of management of immunotherapy-related toxicities and case reports, and proposed treatment recommendation.

Clinical Diagnosis and Treatment Recommendations for Cardiac Adverse Reactions Related to Immune Checkpoint Inhibitor / 中国肺癌杂志

Immunotherapy of malignant tumors has become a hot spot in the field of cancer research and treatment, bringing new hope to patients with advanced cancer. Activation of molecular programmer death protein-1 and T lymphocyte-associated antigen 4-related signaling pathways at the immunological checkpoint can inhibit T lymphocyte activation and thereby block the inflammatory response. Tumor cells achieve immune escape by activating the molecular pathways associated with immune checkpoints. The immune checkpoint inhibitor can wake up T lymphocytes and enhance the body's clearance of tumor cells. However, the role of immune checkpoint inhibitors is not specific to tumor cells, and it can cause side effects of multiple systems including the cardiovascular system while killing tumor cells. We will summarize the relevant cardiac side effects and give advice on how to manage it.

Clinical Diagnosis and Treatment Recommendations for the Pneumonitis Associated with Immune Checkpoint Inhibitor / 中国肺癌杂志

The increasing use of immunocheckpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by immunocheckpoint inhibitors, mainly activated T-cell immunity, may attack normal tissues and organs of the human body and lead to a variety of adverse effects. In the lung, they could induce checkpoint inhibitor associated pneumonitis (CIP). CIP is different from known pulmonary interstitial pneumonitis, and had a potentially fatal risk if it was not being properly treated. We will summarize the characteristics of CIP and give our advice on how to manage immunocheckpoint inhibitor associated pneumonitis.

The Use of Glucocorticoid in the Management of Adverse Effects Related to Immunocheckpoint Inhibitors / 中国肺癌杂志

Immunocheckpoint inhibitors (ICIs) activated the patients' tumor immunity to kill the tumor cell, and brought new hope to patients with tumor. However, a series of immunocheckpoint inhibitors related adverse effects (irAEs) may also occur based on immune injury. Glucocorticoids are the basis for the treatment of such irAEs. However, the usage, dosage and course of treatment of glucocorticoid in irAEs are different from those in classic autoimmune diseases. Meanwhile, long-term use of large doses of glucocorticoids may cause serious adverse effects too. In this paper, the mechanism, dosage forms, adverse effects and management of glucocorticoids are described in detail, providing references and suggestions for oncologists to apply glucocorticoids in clinical practice.

Diagnosis and Treatment Recommendation and Exploration for Critical and Refractory Adverse Effects Related to Immunocheckpoint Inhibitors / 中国肺癌杂志

The application of immunological checkpoint inhibitors (ICIs) has modified many treatment strategies of malignant tumors, which has become a milestone in cancer therapy. The principle of action can be explained as "brake theory". After releasing the brakes by ICIs, unprecedented systemic toxicities, even some refractory and fatal immune-related adverse effects (irAEs) may develop. In this article, we summarized the recommended treatments of grade 3-4 severe irAEs in the latest European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN)/American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC) and Chinese Society of Clinical Oncology (CSCO) guidelines and consensus. We also performed a systemic review of case reports and reviews of irAEs up to May 20, 2019 in PubMed and Chinese journals. Successful applications of specific immunosuppressive drugs and stimulating factors beyond the above guidelines and consensus were supplemented and highlighted, including agents blocking interleukin 6 (IL-6), rituximab, anti-tumor necrosis factor-α (TNFα) monoclonal antibody (mAb), anti-integrin 4 mAb, Janus kinase inhibitors, thrombopoietin receptor agonists and antithymocyte globulin (ATG) etc. We put some concerns of using high-dose steroids for long-term, and emphasize the secondary infections, tumor progression, and unavailability of ICI re-challenge during steroid treatment. We propose the "De-escalation Therapy" principle for severe and refractory irAEs, and suggest that immunosuppressive drugs specifically targeting cytokines should be used as early as possible. Many irAEs in the era of immunotherapy are unprecedented compared with traditional chemotherapy and small-molecule targeted therapy, which is a big challenge to oncologists. Therefore, the establishment of multidisciplinary system is very important for the management of cancer patients.

Efficacy and safety of anlotinib in 16 patients with advanced non-small cell lung cancer / 中华内科杂志

Objective To evaluate the efficacy and safety of anlotinib in patients with advanced non-small cell lung cancer (NSCLC).Methods Patients with stageⅢB/ⅣNSCLC who progressed after two lines or more regimens were randomized into anlotinib group (12 mg daily from day 1 to 14 of a 21-day cycle) or placebo group with ratio of 2:1. Study drugs or placebo were given until disease progression or intolerable toxicity. The primary endpoint was overall survival (OS), and the second endpoints were progression free survival (PFS), objective response rate, and disease control rate. Results Between April 2015 and December 2015, twenty-four patients were assigned at Peking Union Medical College Hospital. The baseline characteristics of the anlotinib group (n=16) and placebo group (n=8) were fairly comparable. The median OS was 12.7 months in anlotinib group and 11.1 months in placebo group (P=0.460). The median PFS was 4.0 months in anlotinib group and 1.4 months in placebo group (P=0.065). The common adverse events were manageable such as hypertension, hand-foot syndrome, thyroiddy sfunction. No drug-related mortality occurred. Conclusions Anlotinib had a trend of improvement in OS and PFS as third-line treatment or beyond in advanced NSCLC compared with placebo with manageable toxicity.

The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung ;cancer patients / 中华内科杂志

Objective To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations.Methods Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study.The response rates , progress free survival ( PFS) , overall survival ( OS ) , and the safety were analyzed.Results Ninety advanced adenocarcinoma patients were enrolled in this study , 44 patients had partial response ( PR ) , 42 patients had stable disease ( SD ) , 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%.The median PFS was 14.9 months (95%CI 13.5-16.3) and the OS was 37.0 weeks ( 95%CI 27.9 -46.1 ).Patients with brain metastases showed higher ORR ( P =0.049 ).Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P=0.007 ).The most common adverse events were grade 1 -2 skin rash (38 patients, 40.9%).Other adverse events included dry skin , oral mucositis, diarrhea and liver function injury.Three patients withdrew because of severe liver injury or skin rash.No treatment related mortality occurred .Conclusions Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.