2018 Vol. 9, No. 3

Editorials
Abstract:
Connective tissue disease (CTD) is a group of systemic disorder characterized by autoimmunity and autoimmune-mediated organ and system damage. The pulmonary complication is an important extra-articular feature of CTD and a major cause of mortality. The key point in the management of CTD-associated interstitial lung disease (CTD-ILD) should focus on the type of ILD, the stage of the disease, and what proper measures should be taken. CTD-ILD is still using the classification of idiopathic interstitial pneumonia. However, there is no authoritative clinical guidance for the diagnosis and treatment of CTD-ILD. More and more studies show that some auto-antibodies are strongly associated with CTD-ILD, which may guide clinical practice. In clinical practice, physicians should particularly pay more attention to CTD patients with insignificant pulmonary manifestations, so as to identify CTD-ILD in the early stage and intervene at the right time to delay the progression.
Abstract:
The definition and clinical classification of pulmonary hypertension (PH) were updated in the 6th World Symposium on Pulmonary Hypertension (WSPH). The hemodynamic definition of PH keeps no change, but pre-capillary PH was redefined as mean pulmonary arterial pressure>20 mm Hg, pulmonary artery wedge pressure < 15 mm Hg and pulmonary vessel resistance>3 WU. The updated clinical classification included:pulmonary arterial hypertension(PAH) with vasoreactivity was added as a subclass of PAH; in drugs and toxins induced PAH, the role of methamphetamines and dasatinib was updated from likely to definite; pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis was changed from 1' to a subclass of PAH; splenectomy and thyroid diseases were withdrawn from the group 5 of PH, etc. These clinical practice updates will guide clinical practice better.
Specialist Forum
Abstract:
Idiopathic interstitial pneumonias (ⅡPs) are a group of heterogeneous diffuse parenchymal lung diseases of unknown etiology, which mainly involve the interstitium of the lung. With the deepening of research, the classification and treatment of ⅡPs have gone through a process of continuous evolution。This article reviewed the changes in the classification of ⅡPs, the evolution of the concept and definition of acute exacerbation of idiopathic pulmonary fibrosis, and the background and latest progress in the treatment plan at different periods of IPF.We also prospected the classification, diagnosis, and treatment of ⅡPs in the future.
Abstract:
Interstitial lung diseases (ILDs) are a group of diverse pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. There are no specific diagnostic methods for ILDs currently and various serum biomarkers, including Krebs von den Lungen-6 (KL-6), have been tested for their use in diagnosing ILDs. However, the pathophysiological role of KL-6 in patients with ILDs is not yet very clear. KL-6 is high-molecular-weight glycoprotein and moderately expressed in type Ⅱ pneumocytes and respiratory bronchiolar epithelial cells. KL-6 has been found to have an association with various types of diseases such as cancers, some neonatal lung diseases, ILDs, and acute lung injury. In this article, we review the structure of KL-6 and the relationship between the elevation of KL-6 and the etiology, progression, treatment evaluation, and prognosis of ILDs.
Guideline Interpretation
Abstract:
The Kidney Disease:Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) was originally published in 2009, which assists practitioners in clinical diagnosis, prevention, and treatment of CKD-MBD. However, the Guideline Work Group acknowledged the lack of sufficient evidence for the base of recommendations. The Guideline included specific research recommendations to encourage investigators to help fill the gaps and bolster the evidence base. With the accumulation of related results of multiple randomized and controlled trials and prospective cohort studies since 2009, 2017 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD represents a selective update on the prior guideline published in 2009. Specifically, the topic areas for which updated recommendations are issued include the diagnosis of bone abnormalities in CKD-MBD, treatment of CKD-MBD by targeting phosphate lowering and calcium maintenance, treatment of parathyroid hormone abnormalities in CKD-MBD, and so on. A total of 12 recommendations were reevaluated and updated based on new data. This report interprets the updates on 2017 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD and describes the results of these proceedings, which highlights the significance of KDIGO CKD-MBD guideline in clinical practice.
Point/Counterpoint
Abstract:
The overall survival(OS) in patients with multiple myeloma (MM) has been prolonged from 3 years to 8-10 years during the past 20 years, which benefits from the broad use of novel agents including proteasome inhibitors and immune modulatory drugs. Even in the era of novel medicines, high-dose melphalan followed by autologous stem cell transplantation (ASCT) is the standard treatment for transplant candidates of newly diagnosed MM. ASCT significantly further improves the post-transplant response rate and the proportion of negative minimal residual disease, as well as leading to better progression-free survival. Nevertheless, the effect of ASCT on OS was not consistent among different clinical trials, which was probably related to different strategies after relapse. As other novel methods including monoclonal antibodies and immune therapies are being developed, more alternatives will be considered. Therefore, ASCT is still the front-line consolidation regimen for transplant candidates with MM.
Abstract:
Autologous stem cell transplantation(ASCT) is a standard choice for the treatment of multiple myeloma (MM). ASCT is an important therapy for MM not only in the era of classical drugs but also in the times of new medicines. As literature reported, the length of progression-free survival of MM patients can be extended by ASCT. But the effect of ASCT on the overall survival is still unknown, especially for high-risk patients with cytogenetic abnormalities. Consolidation and maintenance after the ASCT is very important to maintain the effects of ASCT. It is necessary to be aware of the side effects and second primary malignances after ASCT.
Original Contributions
Abstract:
  Objective   This study aimed to investigate the agreement of central venous oxygen saturation (ScvO2) with mixed venous oxygen saturation (SvO2) in postoperative care of congenital heart disease (CHD)with pulmonary arterial hypertension (PAH).   Methods   Forty-three patients undergoing CHD-PAH repairing surgery were prospectively selected from Henan Provincial People's Hospital, Fuwai Hospital, the Eighth Affiliated Hospital of Sun Yat-sen University, and the First People's Hospital of Guanyuang from March 2016 to March 2017. Data of ScvO2 and SvO2 were synchronously collected after cardiopulmonary bypass (CPB), and 6, 12, 24, and 48 hours after admission to the intensive care unit. In addition, hemodynamic parameters, hemoglobin, and arterial lactate were recorded. Data were analyzed by Bland-Altman test and linear regression analysis.   Results   The overall R2 of ScvO2 to SvO2 for the pooled measurements was 0.369. R2 of post-CPB, 6, 12, 24, 48 hours after admission to the intensive care unit were 0.515, 0.375, 0.605, 0.712, and 0.252, respectively. Bland-Altman test for ScvO2 and SvO2 showed that the mean bias was -1.3% and limits of agreement (LOA) were -17.0% to 14.4%. In general, the influences of oxygen extraction rate (O2ER) (R2=0.030, P < 0.05), pulmonary artery systolic pressure (SPAP) (R2=0.030, P < 0.05), and heart rate (HR) (R2=0.032, P < 0.05) on △ScvO2-SvO2 were relatively small; when ScvO2 was < 70%, the influences of O2ER (R2=0.203, P < 0.01), SPAP (R2=0.110, P < 0.01), and HR (R2=0.150, P < 0.01) were much greater, and ScvO2 would underestimate SvO2; ScvO2 might overestimate SvO2 when ≥ 70%. Bland-Altman test indicated during mechanical ventilation the mean bias of ScvO2 and SvO2 (△ScvO2-SvO2) was -1.3% and LOA were -16.1% to 13.5%, the only factor influencing △ScvO2-SvO2 was O2ER (R2=0.122, P < 0.01); without mechanical ventilation, the mean bias was -1.3% and LOA were -19.5% to 16.8%, and the influence on △ScvO2-SvO2 were O2ER (R2=0.320, P < 0.01) and arterial oxygen saturation (R2=0.320, P < 0.01).   Conclusions   ScvO2 cannot replace SvO2 in postoperative care for patients with CHD-PAH. ScvO2 and SvO2 should be monitored respectively to exclude the hypo-perfusion state when ScvO2 ≥ 70%.
Abstract:
  Objective   The aim of this study was to investigate the status of venous thromboembolism(VTE)in patients in the department of internal medicine and to evaluate whether Padua risk assessment modelcan be applied to this patient population.   Methods   Baseline information, risk factors, prevention, and the incidence of VTE in in-patients of the department of internal medicine were collected and analyzed at Peking Union Medical College Hospital from May 17, 2016, to September 9, 2016. Patients with or without VTE were compared during hospitalization and within 3 months after discharge. Correlations between risk factors and VTE events were calculated and risk stratification was calculated by Padua risk assessment model. The predictive value was assessed by Logistic regression analysis.   Results   A total of 3115 patients were enrolled in this study. The incidence of VTE was 2.5%(78/3115). The sensitivity and specificity of Padua risk assessment model were 83.3% and 62.3%, respectively, and 38.8% of patients had a high risk of VTE based on this model. The four risk factors embodied in the model including elderly age(≥ 70 years), acute myocardial infarction or ischemic stroke, obesity(body mass index ≥ 30 kg/m2), and recent(≤ 1 month)trauma and/or surgery, showed no statistical difference between patients with and without VTE(P>0.05). However, other risk factors that are not included in Padua risk assessment model, i.e. use of estrogen or progesterone, blood transfusion, and mechanical ventilation showed statistically different between VTE and non-VTE patients(P < 0.01). The ratio of receiving preventive treatment with anticoagulant drugs or machines was significantly higher in high-risk patients than those in low-risk ones(P < 0.01); 85.3% of high-risk patients did not receive anticoagulant or mechanical prevention and did not have VTE either.   Conclusions   Padua risk assessment model shows low specificity. Several risk factors and their weight distribution in the model are not suitable, which leads to the limitation of this model in VTE risk assessment for in-patients of the department of internal medicine.
Abstract:
  Objective   To compare the scanning efficiency between the traditional vaginal swab culture and Lim broth subinoculation culture using vaginal-rectal swab for group B Streptococcus (GBS) colonization in late pregnancy.   Methods   A total of 1371 pregnant women who received prenatal care in Peking Union Medical College Hospital from December 2014 to August 2015 were enrolled in the study. Each patient got both kinds of culture in the 35th to 37th week of pregnancy. The positive rate, detection rate, and false negative rate of these two screening methods were compared and analyzed by chi-square test.   Results   The colonization rate of vaginal GBS in late pregnancy was 8.0%. The detection rate of traditional vaginal swab culture was 41.8% with a false negative rate of 58.2%, and the detection rate of vaginal-rectal swab culture was 80.0% with a false negative rate of 20.0%. The difference in the detection rate between these two methods was statistically significant (P < 0.01).   Conclusions   The screening efficiency of Lim broth subinoculation culture using vaginal-rectal swab for GBS colonization in late pregnancy is superior to the traditional vaginal swab culture. Combined application of both methods might improve the detection rate and avoid the missed diagnosis.
Abstract:
  Objective   To evaluate and compare the clinical values of Mycobacterium Spp culture, anti-acid staining and Real-time FQ-PCR assay in the detection of Mycobacterium Spp infection.   Methods   From January 2013 to December 2015, 10 326 specimens of Mycobacterium Spp culture, 25 269 specimens of anti-acid staining and 5949 specimens of Real-time FQ-PCR assay from Peking Union Medical College Hospital were analyzed from the perspectives of specimen distribution and positive isolation rates to compare the difference of thesethree methods and assess their diagnostic values.   Results   From 2013 to 2015, among the methods of detecting Mycobacterium Spp, the main Mycobacterium Spp culture of smear samples were blood specimens(31.4%), while that of anti-acid staining and Real-time FQ-PCR were sputum specimens(40.3% and 40.4%). Mycobacterium Spp isolation rate of Real-time FQ-PCR (8.9%) was significantly higher than those of culture (5.6%) and anti-acid staining (1.9%) (both P < 0.05). Using culture as the gold standard, the sensitivity of Real-time FQ-PCR assay (42.9%) was higher than that of anti-acid staining (31.3%), but the specificity (95.2%) of Real-time FQ-PCR assay was lower than that of anti-acid staining (97.4%) (P < 0.05).   Conclusions   Among the three laboratory diagnostic methods of Mycobacterium Spp, the Real-time FQ-PCR has the advantage of high isolation rate and high sensitivity. It is one of the effective methods for the detection of Mycobacterium Spp.
Review
Abstract:
Idiopathic pulmonary fibrosis(IPF) is a progressive fatal disease of the lung with unknown etiology and limited treatment options. It is more common in men and the elderly aged over 50 years, which also have a high incidence of emphysema, lung neoplasms, and cardiovascular disease. IPF patients with comorbidities often have a worse prognosis than those with IPF alone. We write this article in reference to common comorbidities in patients with idiopathic pulmonary fibrosis to draw physicians' attention. Clinical physicians should know that much can be done to identify and alleviate symptoms of those comorbidities, and to potentially improve the overall quality of life of these patients.
Teaching and Research
Abstract:
In January 2016, a healthy subject in the Phase Ⅰ clinical trial of BIA 10-2474 in France experienced brain death after administration of the studied medicine. In order to explore the cause of this event and systematically mitigate the risk of early-phase clinical trials, this article sorted out the potential reasons in terms of the mechanism of drug effect, preclinical findings, design and execution of the clinical study based on the report written by the Temporary Specialist Scientific Committee involved in the survey of the BIA 10-2474 study. The lessons learnt from this tragedy may include:(1)the decision on clinical development should be made carefully according to available research data and relevant information obtained from similar drugs, so as to improve the rate of success and avoid unnecessary risks; (2)the trial design should consider safety findings and pharmacody-namic properties of the drug in pre-clinical studies, as well as the scientific objectives of the study; (3)in early-stage clinical trials of novel drugs, investigators should be fully aware of the potential risks, even small signals should be noted. Whenever there is an emerging event, it is recommended to perform a comprehensive analysis on the event and then treat it conservatively.
Complicated and Rare Disease
Abstract:
Research on rare diseases is limited by the poor availability of samples. Therefore, treatment of rare diseases is hampered by insufficient understanding of the mechanisms and resultant underdevelopment of viable therapies. With the advent and development of the technology of induced pluripotent stem cells (iPSCs) in recent years, more and more studies have begun to reprogram somatic cells derived from patients into iPSCs, which then differentiate into cells affected by the disease. Through developmental and functional analysis of the differentiated cell types, these stem cell models carrying patient-specific mutations have become an invaluable tool for research on rare diseases. iPSCs technology has revolutionized the ways of exploring the mechanisms of human rare diseases and developing therapies. In particular, the combination of human iPSCs technology with recent development in gene editing and 3D organoids makes iPSC-based platforms even more powerful in each area of their applications, including precision medicine. This review overviews recent advance in human iPSC-based modeling of rare diseases. Additionally, we outline the application of iPSCs technology particularly relevant to drug screening and cell therapy, so as to provide new inspiration for researchers.
Clinical Biobank
Abstract:
  Objective   This study aimed to gauge the current state of biobank business planning in China.   Methods   We conducted a survey among the directors or main participants of 63 biobanks in China. The questionnaire had six categories, including basic information about the biobanks, business planning, utilization, users/customers, marketing/advertising, and cost recovery/performance measures. In this report, we presented a descriptive analysis of the responses in the survey.   Results   In our survey, 96.8% (61/63)of the biobanks belonged to academic institutes or public hospitals; 19.0%(12/63) had business plans; 39.7%(25/63) had a business plan in progress; 41.3%(26/63) had no business plan. In 85.0%(34/40) of the biobanks, the actual utilization rate was less than 20%; and in 97.5%(39/40) of the biobanks, the actual utilization rate of their bio-specimen collections was generally lower than the targeted one. About 88.6%(1084/1223) samples were for internal use but not shared externally.   Conclusions   According to the results of this survey, the situation of biobank business planning in China is not so optimistic. The actual utilization rates of most biobanks were generally lower than their goals, and the main problem was lack of sharing. Cooperation and sharing of domestic biobanks should be further strengthened.
Clinical Research and Evidence Based Medicine
Abstract:
Over time, there have been major changes in the role of doctors and patients in decision-making. Shared Decision Making implies that doctors and patients make a decision jointly after communicating information about treatment options, benefits, and harms, and then considering the patient's values, circumstances and preference. Historical evolution, the reason why we need SDM, patients' perceptions of SDM, and how to implement SDM in clinical practice were introduced in this paper, which illuminated that medicine should be practiced with not only new evidence and techniques but also patient-centered communication skills. With shared decision-making, we can build a good doctor-patient relationship, be aware of patients' preference, and achieve optimal patient care.
2018, 9(3): 281-284. doi: 10.3969/j.issn.1674-9081.2018.03.017
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Abstract:
Clinical Case Analysis
Abstract:
In some patients who have low or no response to antiplatelet drugs, cardiovascular and cerebrovascular events still happen with standard antiplatelet therapy. In this case report, a 63-year-old woman appeared repeated episodes of limb weakness, although she had taken antiplatelet drugs, i.e. aspirin and clopidogrel, for a long time. Every time, magnetic resonance imaging showed that she had a fresh cerebral infarction; and at the same time, platelet aggregation test, clotting test, and gene test indicated clopidogrel and aspirin resistance, which meant low or no response to antiplatelet therapy. We changed immediately to cilostazol and followed up for more than 1 year. This patient had no recurrence of cardiovascular and cerebrovascular events anymore.