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Study of the clinical phenotype of symptomatic chronic airways disease by hierarchical cluster analysis and two-step cluster analyses

Pu NING ; Yanfei GUO ; Tieying SUN ; Hongsheng ZHANG ; Di CHAI ; Xiaomeng LI

Chinese Journal of Internal Medicine.2016;55(9):679-683. doi:10.3760/cma.j.issn.0578-1426.2016.09.005

Objective To study the distinct clinical phenotype of chronic airway diseases by hierarchical cluster analysis and two-step cluster analysis.Methods A population sample of adult patients in Donghuamen community,Dongcheng district and Qinghe community,Haidian district,Beijing from April 2012 to January 2015,who had wheeze within the last 12 months,underwent detailed investigation,including a clinical questionnaire,pulmonary function tests,total serum IgE levels,blood eosinophil level and a peak flow diary.Nine variables were chosen as evaluating parameters,including pre-salbutamol forced expired volume in one second(FEV1)/forced vital capacity (FVC) ratio,pre-salbutamol FEV1,percentage of post-salbutamol change in FEV1,residual capacity,diffusing capacity of the lung for carbon monoxide/alveolar volume adjusted for haemoglobin level,peak expiratory flow (PEF) variability,serum IgE level,cumulative tobacco cigarette consumption (pack-years) and respiratory symptoms (cough and expectoration).Subjects' different clinical phenotype by hierarchical cluster analysis and two-step cluster analysis was identified.Results (1) Four clusters were identified by hierarchical cluster analysis.Cluster 1 was chronic bronchitis in smokers with normal pulmonary function.Cluster 2 was chronic bronchitis or mild chronic obstructive pulmonary disease (COPD) patients with mild airflow limitation.Cluster 3 included COPD patients with heavy smoking,poor quality of life and severe airflow limitation.Cluster 4 recognized atopic patients with mild airflow limitation,elevated serum IgE and clinical features of asthma.Significant differences were revealed regarding pre-salbutamol FEV1/FVC％,pre-salbutamol FEV1％ pred,postsalbutamol change in FEV1 ％,maximal mid-expiratory flow curve (MMEF)％ pred,carbon monoxide diffusing capacity per liter of alveolar(DLCO)/(VA)％ pred,residual volume(RV)％ pred,total serum IgE level,smoking history (pack-years),St.George' s respiratory questionnaire (SGRQ) score,acute exacerbation in the past one year,PEF variability and allergic dermatitis (P ＜ 0.05).(2) Four clusters were also identified by two-step cluster analysis as followings,cluster 1,COPD patients with moderate to severe airflow limitation;cluster 2,asthma and COPD patients with heavy smoking,airflow limitation and increased airways reversibility;cluster 3,patients having less smoking and normal pulmonary function with wheezing but no chronic cough;cluster 4,chronic bronchitis patients with normal pulmonary function and chronic cough.Significant differences were revealed regarding gender distribution,respiratory symptoms,pre-salbutamol FEV1/FVC％,pre-salbutamol FEV1 ％ pred,post-salbutamol change in FEV1 ％,MMEF％ pred,DLCO/VA％ pred,RV％ pred,PEF variability,total serum IgE level,cumulative tobacco cigarette consumption (pack-years),and SGRQ score (P ＜ 0.05).Conclusion By different cluster analyses,distinct clinical phenotypes of chronic airway diseases are identified.Thus,individualized treatments may guide doctors to provide based on different phenotypes.

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The 452th case:rash, hypotension, abdominal pain and headache

Sainan BIAN ; Huaxia YANG ; Qian WANG ; Dong XU ; Yan ZHAO

Chinese Journal of Internal Medicine.2016;55(9):741-744. doi:10.3760/cma.j.issn.0578-1426.2016.09.020

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized with multiple organ involvements.Acute acalculous cholecystitis (AAC) is an extremely rare manifestation of digestive system involvement in SLE.We reported a case of 32-year-old woman who complained skin rashes for two weeks and stomachache and oliguria for one day.She had rashes at onset,and developed fever,stomachache,hypotension and headache.Physical examination at admission indicated blood pressure 76/47mmHg(1 mmHg =0.133 kPa),heart rate 107 beats/min,warm acra.Murphy's sign was positive.Ultrasound suggested the enlarged gallbladder with surrounding hypoecho band yet no biliary calculi were found.A diagnosis of SLE was made,characteristic with distributive shock at the onset and AAC,complicated with neuropsychiatric lupus and lupus nephritis.She had an acute and severe course of disease,which had been relieved after treatment of high dose glucocorticoid and immunosuppressants.This case arouses clinicians to pay more attention to AAC as a rare form of disease flare in SLE.Early diagnosis of AAC is crucial to a favorable prognosis and in avoid of abdominal surgery.

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An analysis of characteristics of nerve conduction in 154 cases of amyotrophic lateral sclerosis

Yuting REN ; Fang CUI ; Fei YANG ; Zhaohui CHEN ; Li LING ; Xusheng HUANG

Chinese Journal of Internal Medicine.2016;55(10):755-758. doi:10.3760/cma.j.issn.0578-1426.2016.10.006

Objective To analyze the features of nerve conduction in patients with amyotrophic lateral sclerosis (ALS),and explore the correlation between compound muscle action potential (CMAP)amplitude and disease duration and revised amyotrophic lateral sclerosis functional rating scale (ALSFRSR).Methods Standard motor and sensory nerve conduction studies were performed in 154 patients with ALS.The following parameters were collected including CMAP amplitude,distal motor latency (DML),motor conduction velocity,sensory conduction velocity and sensory nerve action potential amplitude.Regression study was done to explore the correlation between CMAP amplitude and disease duration and ALSFRS-R.Results Motor nerve conduction abnormalities were presented in a majority of the patients with prolonged DML in the tibial nerve,median nerve and ulnar nerve as the most common form (61.06％-81.42％),followed by decreased CMAP amplitude (30.12％-53.98％),decreased MCV (12.05％-16.81％) and absence of CMAP (2.65％-9.73％).Sensory nerve conduction abnormalities were detected in a small proportion of patients and the decreased SCV,decreased SNAP amplitude and absence of SNAP in the sural nerve,median nerve and ulnar nerve were found in 1.22％-2.73％,0-1.82％ and 0-1.22％patients respectively.No correlation was found between CMAP of the common peroneal nerve,tibial nerve,median nerve and ulnar nerve and the disease duration (P ＞ 0.05),while significant positive correlation was established between CMAP amplitude of the median nerve and ulnar nerve and ALSFRS-R (r =0.273,P =0.016;r =0.357,P =0.001).Conclusions Motor nerve conduction is abnormal in a majority of ALS patients with prolonged DML as the most common form,while abnormal sensory nerve conduction is only found in a few of ALS patients.CMAP amplitude of the median nerve and ulnar nerve might be of certain clinical value in evaluating the severity of ALS.

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The specificity and limitations of sacroiliac joint magnetic resonance imaging in the diagnosis of axial spondyloarthritis in patients with chronic low back pain

Yanyan WANG ; Zheng ZHAO ; Gui LUO ; Yan LI ; Jianglin ZHANG ; Feng HUANG

Chinese Journal of Internal Medicine.2016;55(11):833-839. doi:10.3760/cma.j.issn.0578-1426.2016.11.004

Objective To evaluate the specificity and limitations of sacroiliac joint magnetic resonance imaging (MRI) in the diagnosis of axial spondyloarthritis (SpA)in patients with chronic low back pain.Methods We retrospectively analyzed clinical data of 390 patients with chronic low back pain in Department of Rheumatology,the PLA General Hospital from January 2013 to December 2015,including clinical manifestations,laboratory examinations and MRI data of sacroiliac joints.Results There were 238 men and 152 women recruited.A total of 326 cases were diagnosed as axial SpA,including 216 men and 110 women with mean age (27.10 ± 8.64) years and mean duration (7.64 ± 3.50) months.Among these 326 patients,243 (74.5％) were HLA-B27 positive.The other 64 patients were considered as diagnoses rather than SpA (non-SpA),consisting of 22 men and 42 women with mean age (31.29 ± 7.76) years and mean duration (5.75 ±2.90)months.Non-SpA group had 10 (15.6％) patients with HLA-B27 positive.There were 68.1％ and 65.0％ SpA patients showing bone marrow edema and bone erosion of sacroiliac joint in MRI imaging respectively.Although there were 25.0％ non-SpA patients with bone marrow edema and 7.8 ％ with bone erosion in MRI of sacroiliac joint,the scores of bone marrow edema 0.00 (0.00,0.75) and bone erosion [0.00(0.00,0.00)] were significantly lower compared with those in axial SpA group [bone marrow edema scores 2.00 (0.00,4.00),bone erosion scores 1.00 (0.00,3.00);P ＜ 0.05].The scores of fat infiltration [1.00 (0.00,4.25),1.00 (0.00,4.00)] and bone sclerosis [0.00 (0.00,1.00),0.00(0.00,1.75)] were not statistically different between two groups.Diagnostic sensitivity of bone marrow edema and bone erosion for axial SpA were 56.4％ and 64.1％ respectively,specificity were 93.8％ and 92.2％ respectively.The positive predictive value of bone marrow edema and bone erosion for axial SpA were 9.09 and 8.21,negative predictive value were 0.46 and 0.38.Diagnositic sensitivity of fatty infiltration and bone sclerosis for axial SpA group were 29.1％ and 57.7％,specificity were 64.1％ and 46.9％.The positive predictive value of fatty infiltration and bone sclerosis for axial SpA were 0.81 and 1.08,negative predictive valne were 1.10 and 0.90.Conclusion Sacroiliac joint MRI is a valuable method to diagnose axial SpA in patients with chronic low back pain.Yet it still has some limitations.Clinical presentations and spinal MRI would be helpful in some patients.

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The clinical characteristics of macrophage activation syndrome secondary to systemic lupus erythematosus

Nan JIANG ; Mengtao LI ; Di WU ; Xiaofeng ZENG

Chinese Journal of Internal Medicine.2016;55(11):840-844. doi:10.3760/cma.j.issn.0578-1426.2016.11.005

Objective To investigate the clinical features of macrophage activation syndrome (MAS) associated with systemic lupus erythematosus (SLE).Method The clinical data of 15 patients with SLE-induced MAS diagnosed in Peking Union Medical College Hospital from July 2011 to December 2014 were retrospectively analyzed.Results Fourteen patients were female.The average age was 28.07.When MAS occurred,the average duration of SLE was 20.47 months,and the average SLE disease activity index (SLEDAI) was 18.4.All 15 patients developed fever,hematocytopenia and impaired liver function in the course of MAS,while patients with splenomegaly,coagulation disorders and neuropsychiatric symptoms were 11,14 and 8,respectively.All 15 patients presented leukocpenia and thrombocytopenia.Hypofibrinogenemia,elevated ferritin and hemophagocytosis in bone marrow were respectively observed in 7,11 and 12 patients.Glucocorticoids were used in all patients,among whom eight received pulse methylprednisolone therapy.Thirteen patients were treated with immunosuppressants,including cyclosporine A,tacrolimus,cyclophosphamide and mycophemolate mofetil.Complete remission was achieved in 14 patients.One patient died of MAS.Conclusions In patients with SLE,MAS was most commonly seen in young females with short SLE duration and active disease.Fever,splenomegaly,hematocytopenia,coagulation disorders and liver damage are the most remarkable clinical manifestations.Early diagnosis and intensive therapy are the key parts to improve clinical outcome.

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The impact of cigarette cessation intervention on mental state of patients with coronary heart disease

Zhiming ZHOU ; Xiaohan XU ; Jing LIANG ; Bin HU ; Yujing CHENG ; Chao SHI ; Yujie ZHOU

Chinese Journal of Internal Medicine.2016;55(11):854-858. doi:10.3760/cma.j.issn.0578-1426.2016.11.008

Objective This study was designed to observe the impact of cigarette cessation on anxiety and depression in patients with coronary heart disease (CHD).Methods A total of 690 cigarette smoking patients with CHD identified by coronary angiography (CAG) were included and analyzed in the study.The mental state were scored with Hamilton anxiety (HAMA) and depression (HAMD) scale both on admission and at 6-month follow-up.The patients were divided into two groups based on the cigarette cessation.The score of mental state between the two groups were compared.The patients were treated with percutaneous coronary intervention (PCI),coronary artery bypass grafting (CABG),or medicine therapy (MT).Results The clinic data and score of mental state were similar at the time of admission (HAMA:10.66±5.53 vs 11.09 ±5.61,P =0.311;HAMD:29.81 ± 10.13 vs 28.94 ± 10.22,P =0.266 4) between the two groups.After 6 months,the proportions of subjects in smoking cession group with anxiety (24.2％ vs 32.3％,P ＜0.05),depression (18.0％ vs 27.5％,P ＜0.05),and anxiety and depression (7.0％ vs 16.2％,P ＜0.001) decreased significantly compared with those in smoking group irrespective of the treatment strategy.Both the HAMA and HAMD scores were lower in smoking cessation group (HAMA:9.83±3.40;HAMD:24.91 ±7.90) than in smoking group (HAMA:10.98 ±4.87;HAMD:27.70 ± 11.16) (all P ＜ 0.001).Conclusions Smoking cessation is good for the relief of anxiety and depression in CHD patient.

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A cohort study comparing the efficacy and safety of bortezomib plus dexamethasone versus bortezomib, epirubicin and dexamethasone in patients with multiple myeloma

Qianyun HAO ; Huan CHEN ; Kaiyan LIU ; Lei WEN ; Xiaojun HUANG ; Jin LU

Chinese Journal of Internal Medicine.2016;55(9):689-694. doi:10.3760/cma.j.issn.0578-1426.2016.09.007

Objective Bortezomib plus dexamethasone (BD) and bortezomib,epirubicin plus dexamethasone (PAD) are both front-line regimens of multiple myeloma.This study aimed to assess the efficacy and safety of BD versus PAD regimens in multiple myeloma.Methods All 208 patients with newly diagnosed multiple myeloma using either BD or PAD front-line regimens were enrolled between November 2006 and July 2014.Front-line chemotherapy regimens were 2-7 cycles.Response rates,overall survival,progression-free survival,and adverse effects were retrospectively analyzed.Results (1) In PAD group,the overall response rate was 82.9％ [complete response(CR) 28.6％,very good partial response(VGPR) 12.9％],which was similar as that in BD group [70.3％ (CR 26.8％,VGPR 5.1％),P =0.049].The estimated median progression-free survival was 34.0 months in PAD group versus 25.0 months in BD group (P =0.010).(2) The triplet regimen has a higher accumulated response rate along with chemotherapy cycles,but it didn't show any difference with the doublet regimen.(3) In elderly patients (＞ 65 years old),the overall response rates in two groups had no significant difference (P =0.769),while in patients ≤65 years old,PAD regimen were more effective than BD regimen (P =0.037).(4) Grade 3 and 4 adverse events were recorded with a higher number of patients in the PAD group than those in the BD group.Conclusions Compared with BD regimen,PAD regimen improves the initial response rates,especially deep responses,as well as progression-free survival in patients with newly diagnosed multiple myeloma.However,more severe toxicities are accordingly higher.In elderly patients,overall response rate,estimated median progression-free survival,and median overall survival are all comparable in both regimens.

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The role of four criteria in assessment of the severity and prognosis of hyperlipidemic acute pancreatitis

Lixin YANG ; Lichuan DU ; Xin LIU ; Jing CHEN ; Jianyu HAO

Chinese Journal of Internal Medicine.2016;55(9):695-699. doi:10.3760/cma.j.issn.0578-1426.2016.09.008

Objective To explore the four criteria,including bedside index for severity in acute pancreatitis(BISAP),Ranson score,modified CT severity index(MCTSI) and acute physiology and chronic health evaluation scoring system Ⅱ (APACHE Ⅱ) in assessment of severity and prognosis of hyperlipidemic acute pancreatitis.Methods A total of 326 patients with hyperlipidemic acute pancreatitis were studied retrospectively from August 2006 to July 2015.The discrepancy of the four criteria in assessment of severity and prognosis of hyperlipidemic acute pancreatitis was compared with chi-square test and receiver operating characteristic curve.Results The incidences of moderately severe acute pancreatitis and severe acute pancreatitis,local complications and mortality of patients with BISAP score ≥3,Ranson score ≥3,APACHE Ⅱ score≥8 and MCTSI score≥4 were significantly higher than BISAP score ＜ 3,Ranson score ＜ 3,APACHE Ⅱ score ＜ 8 and MCTSI ＜ 4 respectively (all P ＜ 0.05).As far as severity was concerned,the sensitivity and AUC of APACHE Ⅱ were 57％ and 0.814,which were higher than the other systems.The second most sensitive criterion was BISAP.In assessment of local complications,the sensitivity and AUC of MCTSI were 68％ and 0.791,which were higher than the other three.The most sensitive criterion to predict mortality was BISAP with sensitivity 89％ and AUC 0.867,which was followed by APACHE Ⅱ.Conclusions All four criteria can be used to determine the severity,local complications and mortality.Generally,BISAP is simple and easy to practice,and better than the other three.

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Effect of ginsenoside pre-treatment on 5-hydroxytryptamine system in SD rats with myocardial infarction and depression

Meiyan LIU ; Lijun ZHANG ; Mengchao LIU

Chinese Journal of Internal Medicine.2016;55(9):700-704. doi:10.3760/cma.j.issn.0578-1426.2016.09.009

Objective To evaluate the effect of ginsenoside pre-treatment on serotonin (5-hydroxytryptamine,5-HT),5-HT2A receptor (5-HT2A R),and 5-HT transporter (serotonin transporter,SERT) in serum,platelet lysate and brain tissue homogenates in SD rats with myocardial infarction (MI) or depression.Methods Eighty SD rats were randomized treated with ginsenoside or normal saline (NS).After 4 weeks,the rats were,then,randomized to four subgroups:the MI,the depression,the MI in combination with depression and sham subgroups.5-HT,5-HT2A R and SERT levels were detected in serum,platelet or brain.Results In the NS pre-treatment groups,serum 5-HT levels in sham rats (237.1 ± 32.0)pg/ml were higher than in MI (58.0 ± 11.6) pg/ml,depression (72.8 ± 2.3) pg/ml,and MI with depression rats (62.5 ± 10.2) pg/ml (all P =0.000).Pre-treatment of ginsenoside increased serum and platelet 5-HT in MI,depression and MI with depression rats compared with each corresponding NS treated subgroups (all P ＜ 0.005).However,treatment of ginsenoside lowered the 5-HT2A R expression in MI,depression,and MI with depression subgroups both in platelet and brain tissue homogenates compared with each corresponding NS treated subgroups (all P ＜ 0.05).As to SERT in platelet,treatment of ginsenoside increased its levels in depression rats (P =0.019),but lowered the levels in MI rats (P =0.001) compared with NS treated rats.There were no differences in brain 5-HT and SERT between ginsenoside and NS treated groups.Conclusions The 5-HT system responses differently to ginsenoside treatment under different cardiac and mental stress conditions.Ginsenoside plays an important role in regulation of 5-HT system.

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Chronic hypoxia increases intracellular Ca2+ concentration and augments proliferation by enhancing store-operated Ca2+ entry in pulmonary arterial smooth muscle cells

Gongyong PENG ; Juan XU ; Rongmin LIU ; Wei HONG ; Xinming HE ; Yunen LIN

Chinese Journal of Internal Medicine.2016;55(9):705-709. doi:10.3760/cma.j.issn.0578-1426.2016.09.010

Objective To determine whether store-operated Ca2+ entry (SOCE) is involved in chronic hypoxia-induced alteration of intracellular Ca2 + concentration ([Ca2+] i) and proliferation in pulmonary arterial smooth muscle cells (PASMC).Methods Rat PASMCs were cultured and treated in normoxia (21％O2) or hypoxia (4％ O2) condition.The proliferation of PASMC was detected by cell counting kit-8 (CCK-8) assay.[Ca2 +] i,SOCE and the effects of store-operated Ca2 + channel (SOCC) inhibitors,SKF96365 and NiCl2,on SOCE in hypoxic PASMCs were tested by InCyte [Ca2 +] i measurement system.Results Hypoxia for 24-60 h augmented PASMC proliferation (1.12 ± 0.09 vs 0.71 ± 0.05,P ＜ 0.05) and [Ca2 +] i [(214.8 ± 20.4) nmol/L vs (115.2 ± 13.2) nmol/L,P ＜ 0.05] in a time-dependent manner with the maximum effect at 60 h.Perfusion of Ca2+-free Krebs solution containing nifedipine (5 μ mol/L),cyclopiazonic acid (CPA,10 μmol/L) in PASMCs caused a small transient increase of [Ca2+]i with peak [Ca2+]i (113.3 ± 49.3) nmol/L.Chronic hypoxia (4％ O2,60 h) enhanced [Ca2+]i level with peak value of (193.2 ± 22.7) nmol/L (P ＜ 0.05) in PASMC.After restoration of extracellular Ca2+,CPA caused marked increase of [Ca2+]i with peak value of (328.0 ± 56.7) nmol/L.Chronic hypoxia strengthened CPA-induced increase of [Ca2 +] i with peak value of (526.0 ± 33.7) nmol/L (P ＜ 0.05) in PASMCs.Either SKF96365 50 μmol/L or NiCl2 500 μmol/L distinctly attenuated CPA-induced enhancement of [Ca2 +] i,the peak value of which dropped from (526.0 ± 33.7) nmol/L to (170.4 ± 26.4) nmol/L (P＜0.05) or (177.4±45.9) nmol/L (P＜0.05) respectively.Conclusion Chronic hypoxia boosts the release of Ca2+ from sarcoplasmic reticulum and promotes the activity of SOCC and SOCE,leading to [Ca2 +] i elevation and proliferation of rat PASMCs.

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