目的评估长期大环内酯类抗生素治疗非囊性纤维化支气管扩张症的疗效与风险。方法分别检索中国知网、万方数据、中国生物医学网、维普网、PubMed、Embase、Cochrane Library及Web of Science数据库中已发表的关于长期大环内酯类抗生素治...目的评估长期大环内酯类抗生素治疗非囊性纤维化支气管扩张症的疗效与风险。方法分别检索中国知网、万方数据、中国生物医学网、维普网、PubMed、Embase、Cochrane Library及Web of Science数据库中已发表的关于长期大环内酯类抗生素治疗非囊性纤维化支气管扩张症疗效与风险的随机对照研究。主要结局指标为急性发作频率、24 h痰量改变、炎症指标改变、菌群分布变化与菌群耐药变化。结果共纳入11项随机对照试验,长期大环内酯类抗生素治疗显著降低非囊性纤维化支气管扩张症的急性加重频率,包括至少发生一次急性加重人数(RR=0.63,95%CI:0.46~0.86,P=0.004)和人均急性加重次数(MD=-1.29,95%CI:-1.72~-0.86,P<0.00001)以及降低24 h痰量(MD=-8.10,95%CI:-12.62~-3.58,P=0.0004)。亚组分析显示,3个月以上大环内酯类抗生素治疗可有效降低成年患者急性加重频率。在3个月以下疗程亚组、红霉素治疗亚组以及儿童患者亚组中,大环内酯类抗生素未显著降低急性加重频率。患者种族差异未对治疗效果产生明显影响。基线水平常见痰菌种类及数量、治疗结束后的痰菌种类及数量、治疗结束后痰菌的增加和清除率指标在大环内酯类抗生素治疗组和对照组之间的差异均无统计学意义,但大环内酯类抗生素治疗组的痰菌耐药率显著增加。结论3个月以上大环内酯类抗生素治疗可以显著降低成人非囊性纤维化支气管扩张症患者的急性加重频率,减少24 h痰量。长期大环内酯类抗生素治疗对非囊性纤维化支气管扩张症患者痰菌分布及变化无显著影响,但有提高耐大环内酯类抗生素细菌比例的风险。展开更多
BACKGROUND The common computed tomography findings of pulmonary Langerhans cell histiocytosis (PLCH) are multiple cysts and micronodules predominantly in middle to upper lung lobes.Non-cystic nodules and large nodules...BACKGROUND The common computed tomography findings of pulmonary Langerhans cell histiocytosis (PLCH) are multiple cysts and micronodules predominantly in middle to upper lung lobes.Non-cystic nodules and large nodules are atypical findings of PLCH.CASE SUMMARY The patient was a 48-year-old Japanese man with a smoking history (20 cigarettes/d,28 years) and no symptoms.Multiple nodules existed in all lung lobes,predominantly in the right lower lobe.Some nodules seemed to be distributed randomly,and others were adjacent to bronchus.Most nodules were solid;some small ones were cystic.The largest nodule was 22 mm in diameter.Although metastatic lung tumors were suspected,thoracoscopic lung biopsy led to the diagnosis of PLCH.At 6 months after he quit smoking,all nodules had almost disappeared.We investigated the characteristics of nodules at diagnosis in detail.Of 349 nodules in total,116 were in upper and 199 were in lower lobes.Ninety-six (27.5%) were cystic;the remaining 253 (72.5%) were non-cystic.The prevalence of cystic nodules was higher in upper lobes than in lower lobes (right upper 37.5% vs lower 18.2%,P = 0.0068;left upper 48.1% vs lower 24.4%,P = 0.0078).The average size (dia.) of cystic nodules was smaller than that of noncystic nodules (5.03 mm vs 7.40 mm,respectively,P < 0.0001).CONCLUSION Although multiple non-cystic nodules including large nodules (over 20 mm) are atypical,PLCH should be included in differential diagnoses.The presence of small cystic nodules predominantly in upper lobes and asymptomatic situation are also important for differential diagnoses to distinguish from metastatic cancers.展开更多
Pancreatic carcinoma occasionally associated with prominent mucin production and this type of tumor designated as PCM (pancreatic carcinoma with prominent mucin production) was diagnosed depends on subjective estimati...Pancreatic carcinoma occasionally associated with prominent mucin production and this type of tumor designated as PCM (pancreatic carcinoma with prominent mucin production) was diagnosed depends on subjective estimation of the amount of mucous area, and there has been no report on a quantitative evaluation of the amount of mucinous area in the tumor. To examine the feature of PCM, we analyzed 9 cases of PCM among 243 cases of pancreas carcinoma and evaluated the amount of mucin by imaging analysis. Morphologically, 5 cases were classified as intradactal papillary mucinous neoplasms (IPMN)-derived PCM and 4 cases were as ductal adenocarcinoma (DA)-derived PCM. Mucous composition was found to be more than 50% in all IPMN-derived PCM cases, and that was 40% - 50% in DA-derived PCM cases with one exception. IPMN-derived PCM cases showed expansive growth with pancreatic duct dilatation filled with mucin, while DA-derived PCM cases possessed mucin infiltration into interstitial tissue. Immunohisto-chemically, three of 4 DA-derived PCM cases were MUC1(–)/MUC2(+), and the results of expressions for p16 and Dpc4 suggesting that DA-derived PCM was similar to IPMN-derived PCM rather than ordinary DA. Survival rate of DA-derived PCM cases was lower than that of IPMN-derived PCM cases. We advocate that DA-derived PCM may constitute a borderline group between IPMN and ordinary DA.展开更多
BACKGROUND Hepatic steatosis is a common form of cystic fibrosis associated liver disease(CFLD)seen in an estimated 15%-60%of patients with cystic fibrosis(CF).The pathophysiology and health implications of hepatic st...BACKGROUND Hepatic steatosis is a common form of cystic fibrosis associated liver disease(CFLD)seen in an estimated 15%-60%of patients with cystic fibrosis(CF).The pathophysiology and health implications of hepatic steatosis in cystic fibrosis remain largely unknown.In the general population,hepatic steatosis is strongly associated with insulin resistance and type 2 diabetes.Cystic fibrosis related diabetes(CFRD)impacts 40%-50%of CF adults and is characterized by both insulin insufficiency and insulin resistance.We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than cystic fibrosis patients without diabetes.AIM To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF.METHODS Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study.Only pancreatic insufficient patients with CFRD or normal glucose tolerance(NGT)were included.Patients with established CFLD,end stage lung disease,or persistently elevated liver enzymes were excluded.Mean magnetic resonance imaging(MRI)proton density fat fraction(PDFF)was obtained for all participants.Clinical characteristics[age,sex,body mass index,percent predicted forced expiratory volume at 1 s(FEV1),lumacaftor/ivacaftor use]and blood chemistries were assessed for possible association with hepatic steatosis.Hepatic steatosis was defined as a mean MRI PDFF>5%.Patients were grouped by diabetes status(CFRD,NGT)and cystic fibrosis transmembrane conductance regulator(CFTR)modulator use(lumacaftor/ivacaftor,no lumacaftor/ivacaftor)to determine between group differences.Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher’s exact test.RESULTS Twenty subjects were included in the final analysis.The median age was 22.3 years(11.3-39.0)and median FEV1 was 77%(33%-105%).Twelve subjects had CFRD and 8 had NGT.Nine subjects were receiving lumacaftor/ivacaftor.The median PDFF was 3.0%(0.0%-21.0%).Six subjects(30%)had hepatic steatosis defined as PDFF>5%.Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor(median,range)(2.0%,0.0%-6.4%)than in patients not receiving lumacaftor/ivacaftor(4.1%,2.7-21.0%),P=0.002.Though patients with CFRD had lower PDFF(2.2%,0.0%-14.5%)than patients with NGT(4.9%,2.4-21.0%)this did not reach statistical significance,P=0.06.No other clinical characteristic was strongly associated with hepatic steatosis.CONCLUSION Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis.No association between CFRD and hepatic steatosis was found in this cohort.展开更多
AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis(CF) patients with hepatic steatosis as compared to normal CF controls.METHODS We performed a retrospective review of ad...AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis(CF) patients with hepatic steatosis as compared to normal CF controls.METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging(ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls.RESULTS Data was collected on 114 patients meeting inclusion criteria. Seventeen patients(14.9%) were found to have hepatic steatosis on imaging. Being overweight(BMI > 25)(P = 0.019) and having a higher pp FEV1(75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level(27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes.CONCLUSION Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher pp FEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.展开更多
<strong>Objective:</strong><span style="font-family:Verdana;"> To determine and compare the effect of vitamin D3 supplementation on modifying the disease severity in cystic fibrosis (CF) an...<strong>Objective:</strong><span style="font-family:Verdana;"> To determine and compare the effect of vitamin D3 supplementation on modifying the disease severity in cystic fibrosis (CF) and non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis pediatric patients.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">A randomized clinical trial evaluating the role of oral vitamin D3 supplementation for six months, was performed in forty patients with CF and non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis under the age of 18 years with vitamin D deficiency or insufficiency. The primary outcome was to reach the sufficient Vitamin D level, the secondary outcome was to reevaluate bronchiectasis severity by following up the frequency, severity of pulmonary exacerbations and lung function after vitamin D3 supplementation.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Results:</span></b><b><span style="font-family:""> </span></b><span style="font-family:Verdana;">Forty patients completed the trial. The percentage of improvement of vitamin D level after vitamin D3 supplementation for six months was significantly higher in CF (88.3%) than non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis patients (59.82%)</span><span style="font-family:""> </span><span style="font-family:Verdana;">(P =</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.03).</span><span style="font-family:""> </span><span style="font-family:Verdana;">Additionally, moderate to severe pulmonary exacerbations significantly decreased by more than 60%, 45% (P</span><span style="font-family:""> </span><span style="font-family:Verdana;">=</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.001,</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.005) and frequent exacerbations decreased by 15%, 10% (P</span><span style="font-family:""> </span><span style="font-family:Verdana;">=</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.327, 0.490), while the forced expiratory volume in 1 (FEV1) significantly increased by 17% and 15% in non CF bronchiectasis and CF patients respectively (p</span><span style="font-family:""> </span><span style="font-family:Verdana;"><</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">0.001).</span><b><span style="font-family:Verdana;"> Conclusions: </span></b><span style="font-family:Verdana;">Vitamin D3 therapy was effective in decreasing the frequency and severity of pulmonary exacerbations and preserving lung function. Thereby, improving the disease severity even more in non</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis than CF patients.</span>展开更多
文摘BACKGROUND The common computed tomography findings of pulmonary Langerhans cell histiocytosis (PLCH) are multiple cysts and micronodules predominantly in middle to upper lung lobes.Non-cystic nodules and large nodules are atypical findings of PLCH.CASE SUMMARY The patient was a 48-year-old Japanese man with a smoking history (20 cigarettes/d,28 years) and no symptoms.Multiple nodules existed in all lung lobes,predominantly in the right lower lobe.Some nodules seemed to be distributed randomly,and others were adjacent to bronchus.Most nodules were solid;some small ones were cystic.The largest nodule was 22 mm in diameter.Although metastatic lung tumors were suspected,thoracoscopic lung biopsy led to the diagnosis of PLCH.At 6 months after he quit smoking,all nodules had almost disappeared.We investigated the characteristics of nodules at diagnosis in detail.Of 349 nodules in total,116 were in upper and 199 were in lower lobes.Ninety-six (27.5%) were cystic;the remaining 253 (72.5%) were non-cystic.The prevalence of cystic nodules was higher in upper lobes than in lower lobes (right upper 37.5% vs lower 18.2%,P = 0.0068;left upper 48.1% vs lower 24.4%,P = 0.0078).The average size (dia.) of cystic nodules was smaller than that of noncystic nodules (5.03 mm vs 7.40 mm,respectively,P < 0.0001).CONCLUSION Although multiple non-cystic nodules including large nodules (over 20 mm) are atypical,PLCH should be included in differential diagnoses.The presence of small cystic nodules predominantly in upper lobes and asymptomatic situation are also important for differential diagnoses to distinguish from metastatic cancers.
文摘Pancreatic carcinoma occasionally associated with prominent mucin production and this type of tumor designated as PCM (pancreatic carcinoma with prominent mucin production) was diagnosed depends on subjective estimation of the amount of mucous area, and there has been no report on a quantitative evaluation of the amount of mucinous area in the tumor. To examine the feature of PCM, we analyzed 9 cases of PCM among 243 cases of pancreas carcinoma and evaluated the amount of mucin by imaging analysis. Morphologically, 5 cases were classified as intradactal papillary mucinous neoplasms (IPMN)-derived PCM and 4 cases were as ductal adenocarcinoma (DA)-derived PCM. Mucous composition was found to be more than 50% in all IPMN-derived PCM cases, and that was 40% - 50% in DA-derived PCM cases with one exception. IPMN-derived PCM cases showed expansive growth with pancreatic duct dilatation filled with mucin, while DA-derived PCM cases possessed mucin infiltration into interstitial tissue. Immunohisto-chemically, three of 4 DA-derived PCM cases were MUC1(–)/MUC2(+), and the results of expressions for p16 and Dpc4 suggesting that DA-derived PCM was similar to IPMN-derived PCM rather than ordinary DA. Survival rate of DA-derived PCM cases was lower than that of IPMN-derived PCM cases. We advocate that DA-derived PCM may constitute a borderline group between IPMN and ordinary DA.
基金Supported by a grant from the University Hospitals Fellowship Research Award Program(FRAP)
文摘BACKGROUND Hepatic steatosis is a common form of cystic fibrosis associated liver disease(CFLD)seen in an estimated 15%-60%of patients with cystic fibrosis(CF).The pathophysiology and health implications of hepatic steatosis in cystic fibrosis remain largely unknown.In the general population,hepatic steatosis is strongly associated with insulin resistance and type 2 diabetes.Cystic fibrosis related diabetes(CFRD)impacts 40%-50%of CF adults and is characterized by both insulin insufficiency and insulin resistance.We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than cystic fibrosis patients without diabetes.AIM To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF.METHODS Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study.Only pancreatic insufficient patients with CFRD or normal glucose tolerance(NGT)were included.Patients with established CFLD,end stage lung disease,or persistently elevated liver enzymes were excluded.Mean magnetic resonance imaging(MRI)proton density fat fraction(PDFF)was obtained for all participants.Clinical characteristics[age,sex,body mass index,percent predicted forced expiratory volume at 1 s(FEV1),lumacaftor/ivacaftor use]and blood chemistries were assessed for possible association with hepatic steatosis.Hepatic steatosis was defined as a mean MRI PDFF>5%.Patients were grouped by diabetes status(CFRD,NGT)and cystic fibrosis transmembrane conductance regulator(CFTR)modulator use(lumacaftor/ivacaftor,no lumacaftor/ivacaftor)to determine between group differences.Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher’s exact test.RESULTS Twenty subjects were included in the final analysis.The median age was 22.3 years(11.3-39.0)and median FEV1 was 77%(33%-105%).Twelve subjects had CFRD and 8 had NGT.Nine subjects were receiving lumacaftor/ivacaftor.The median PDFF was 3.0%(0.0%-21.0%).Six subjects(30%)had hepatic steatosis defined as PDFF>5%.Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor(median,range)(2.0%,0.0%-6.4%)than in patients not receiving lumacaftor/ivacaftor(4.1%,2.7-21.0%),P=0.002.Though patients with CFRD had lower PDFF(2.2%,0.0%-14.5%)than patients with NGT(4.9%,2.4-21.0%)this did not reach statistical significance,P=0.06.No other clinical characteristic was strongly associated with hepatic steatosis.CONCLUSION Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis.No association between CFRD and hepatic steatosis was found in this cohort.
文摘AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis(CF) patients with hepatic steatosis as compared to normal CF controls.METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging(ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls.RESULTS Data was collected on 114 patients meeting inclusion criteria. Seventeen patients(14.9%) were found to have hepatic steatosis on imaging. Being overweight(BMI > 25)(P = 0.019) and having a higher pp FEV1(75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level(27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes.CONCLUSION Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher pp FEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.
文摘<strong>Objective:</strong><span style="font-family:Verdana;"> To determine and compare the effect of vitamin D3 supplementation on modifying the disease severity in cystic fibrosis (CF) and non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis pediatric patients.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">A randomized clinical trial evaluating the role of oral vitamin D3 supplementation for six months, was performed in forty patients with CF and non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis under the age of 18 years with vitamin D deficiency or insufficiency. The primary outcome was to reach the sufficient Vitamin D level, the secondary outcome was to reevaluate bronchiectasis severity by following up the frequency, severity of pulmonary exacerbations and lung function after vitamin D3 supplementation.</span><span style="font-family:""> </span><b><span style="font-family:Verdana;">Results:</span></b><b><span style="font-family:""> </span></b><span style="font-family:Verdana;">Forty patients completed the trial. The percentage of improvement of vitamin D level after vitamin D3 supplementation for six months was significantly higher in CF (88.3%) than non</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis patients (59.82%)</span><span style="font-family:""> </span><span style="font-family:Verdana;">(P =</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.03).</span><span style="font-family:""> </span><span style="font-family:Verdana;">Additionally, moderate to severe pulmonary exacerbations significantly decreased by more than 60%, 45% (P</span><span style="font-family:""> </span><span style="font-family:Verdana;">=</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.001,</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.005) and frequent exacerbations decreased by 15%, 10% (P</span><span style="font-family:""> </span><span style="font-family:Verdana;">=</span><span style="font-family:""> </span><span style="font-family:Verdana;">0.327, 0.490), while the forced expiratory volume in 1 (FEV1) significantly increased by 17% and 15% in non CF bronchiectasis and CF patients respectively (p</span><span style="font-family:""> </span><span style="font-family:Verdana;"><</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">0.001).</span><b><span style="font-family:Verdana;"> Conclusions: </span></b><span style="font-family:Verdana;">Vitamin D3 therapy was effective in decreasing the frequency and severity of pulmonary exacerbations and preserving lung function. Thereby, improving the disease severity even more in non</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">CF bronchiectasis than CF patients.</span>
