Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of...Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.展开更多
BACKGROUND Confined placental mosaicism(CPM)is one of the major reasons for discrepancies between the results of non-invasive prenatal testing(NIPT)and fetal karyotype analysis.CASE SUMMARY We encountered a primiparou...BACKGROUND Confined placental mosaicism(CPM)is one of the major reasons for discrepancies between the results of non-invasive prenatal testing(NIPT)and fetal karyotype analysis.CASE SUMMARY We encountered a primiparous singleton pregnant woman with a rare CPM consisting of 47,XY,+21;47,XXY;and 46,XY,who obtained a false-positive result on NIPT with a high risk for trisomy 21.Copy-number variation sequencing on amniotic fluid cells,fetal tissue,and placental biopsies showed that the fetal karyotype was 47,XXY,while the placenta was a rare mosaic of 47,XY,+21;47,XXY;and 46,XY.CONCLUSION The patient had a rare CPM consisting of 47,XY,+21;47,XXY;and 46,XY,which caused a discrepancy between the result of NIPT and the actual fetal karyotype.It is important to remember that NIPT is a screening test,not a diagnostic test.Any positive result should be confirmed with invasive testing,and routine ultrasound examination is still necessary after a negative result.展开更多
Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorio...Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorionic villus and amniotic fluid sampling, which result in a significant risk for pregnancy loss. The discovery of cell free fetal DNA circulating in the maternal blood has great potential for the development of non-invasive prenatal testing(NIPT) methodologies. Such strategies have been successfully applied for the determination of the fetal rhesus status and inherited monogenic disease but the field of fetal aneuploidy investigation seems to be more challenging. The main reason for this is that the maternal cell free DNA in the mother's plasma is far more abundant, and because it is identical to half of the corresponding fetal DNA. Approaches developed are mainly based on next generation sequencing(NGS) technologies and epigenetic genetic modifications, such as fetal-maternal DNA differential methylation. At present, genetic services for non-invasive fetal aneuploidy detection are offered using NGS-based approaches but, for reasons that are presented herein, they still serve as screening tests which are not readily accessed by the majority of couples. Here we discuss the limitations of both strategies for NIPT and the future potential of the methods developed.展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignancies in the world and it is one of the main complications of cirrhosis and portal hypertension.Even in the presence of a well-established follow-up protoc...Hepatocellular carcinoma(HCC)is one of the most common malignancies in the world and it is one of the main complications of cirrhosis and portal hypertension.Even in the presence of a well-established follow-up protocol for cirrhotic patients,to date poor data are available on predictive markers for primary HCC occurrence in the setting of compensated advanced chronic liver disease patients(cACLD).The gold standard method to evaluate the prognosis of patients with cACLD,beyond liver fibrosis assessed with histology,is the measurement of the hepatic venous pressure gradient(HVPG).An HVPG≥10 mmHg has been related to an increased risk of HCC in cACLD patients.However,these methods are burdened by additional costs and risks for patients and are mostly available only in referral centers.In the last decade increasing research has focused on the evaluation of several,simple,non-invasive tests(NITs)as predictors of HCC development.We reviewed the currently available literature on biochemical and ultrasound-based scores developed for the noninvasive evaluation of liver fibrosis and portal hypertension in predicting primary HCC.We found that the most reliable methods to assess HCC risk were the liver stiffness measurement,the aspartate aminotransferase to platelet ratio index score and the fibrosis-4 index.Other promising NITs need further investigations and validation for different liver disease aetiologies.展开更多
AIM To explore the effect of alanine aminotransferase(ALT) on the performance of non-invasive fibrosis tests in chronic hepatitis B(CHB) patients. METHODS A total of 599 treatment-naive and biopsy-proven CHB patients ...AIM To explore the effect of alanine aminotransferase(ALT) on the performance of non-invasive fibrosis tests in chronic hepatitis B(CHB) patients. METHODS A total of 599 treatment-naive and biopsy-proven CHB patients were included in the study. The cohort was divided into the following three groups: Normal ALT(ALT ≤ 40), slightly elevated ALT(40 < ALT ≤ 80) and elevated ALT(ALT > 80). The diagnostic performance of five common non-invasive fibrosis tests for liver fibrosis(stages S2-4), including the aspartate aminotransferase(AST)-to-platelet(PLT) ratio index(APRI), fibrosis index based on 4 factors(FIB-4), King's score, Forns index and gamma-glutamyl transpeptidase(GGT)-to-PLT ratio(GPR), were evaluated for each group. RESULTS Higher ALT levels were associated with higher non-invasive fibrosis test scores. Patients with the same fibrosis stage but higher ALT levels showed higher noninvasive test scores. The areas under the receiver operating characteristics curves(AUROCs) of the noninvasive tests for prediction of ≥ S2 were higher for patients with ALT ≤ 40 U/L(range 0.705-0.755) and 40 < ALT ≤ 80 U/L(range 0.726-0.79) than for patients with ALT > 80 U/L(range 0.604-0.701). The AUROCs for predicting ≥ S3 and S4 were higher in patients with ALT ≤ 40 U/L(range 0.736-0.814 for ≥ S3, 0.79-0.833 for S4) than in patients with 40 < ALT ≤ 80 U/L(range 0.732-0.754 for ≥ S3, range 0.626-0.723 for S4) and ALT > 80 U/L(range 0.7-0.784 for ≥ S3, range 0.662-0.719 for S4). The diagnostic accuracy of the non-invasive tests decreased in a stepwise manner with the increase in ALT.CONCLUSION ALT has a significant effect on the diagnostic performance of non-invasive fibrosis tests. The ALT level should be considered before performing these noninvasive tests.展开更多
Background: Chronic heart failure is a public health problem worldwide. It has a high mortality rate and is accompanied by a decreased functional capacity and alteration of the quality of life. Objective: This st...Background: Chronic heart failure is a public health problem worldwide. It has a high mortality rate and is accompanied by a decreased functional capacity and alteration of the quality of life. Objective: This study aimed to assess the cardiovascular functional capacity of a group of patients suffering from heart failure using the 6-minute walk test (6 MWT). Methods: This was a cross-sectional study carried out in the cardiology unit of Douala’s general hospital for 4 months. We included all eligible patients aged 18 years or more who had stable chronic heart failure and gave informed consent. Those who had an acute coronary syndrome (≤1 month), tachycardia (HR ≥ 120 bpm), high blood pressure (SBP ≥ 180 mmHg and/or DBP ≥ 100 mmHg) and reduced mobility due to orthopaedic reasons were excluded. A 6 MWT was done according to the American Thoracic Society guidelines. The 6 MWT result was considered poor for - 450 m and good for >450 m. Results: We recruited a total of 81 patients (61.7% women) with a mean age of 65.9 ± 10.6 years. The most frequent risk factor for heart failure was high blood pressure (77.8%), alcohol consumption(69.1%) and a sedentary lifestyle (53.1%). The left ventricular ejection fraction was mostly preserved (42.0%) or mildly altered (46.9). The 6 MWT results were poor in 55.6% of cases, average in 19.8% of cases and good in only 24.7% of cases. More than half (59.3%) of the participants perceived the effort as being difficult. The cardiovascular functional capacity was significantly associated with age, heart failure stage and physical activity (p Conclusion: Most patients suffering from chronic stable heart failure in the general hospital of Douala have poor cardiovascular functional capacity.展开更多
Background: Non-invasive markers which use routine laboratory tests are less expensive and highly needed to assess and stage liver fibrosis in chronic hepatitis B patients in Sub-Saharan Africa. We aimed at evaluating...Background: Non-invasive markers which use routine laboratory tests are less expensive and highly needed to assess and stage liver fibrosis in chronic hepatitis B patients in Sub-Saharan Africa. We aimed at evaluating liver fibrosis, using the Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis Index Based on 4 factors (FIB4), and Gamma-glutamyl transpeptidase to Platelet Ratio (GPR) in chronic hepatitis B patients with transient elastography as the reference so as to choose an alternative to transient elastography. Method: We carried out a cross-sectional study using the records of patients who attended the Douala General Hospital and Marie O Polyclinic Douala from 2012 to 2017. Non-invasive tests were compared with Transient Elastography. The Spearman coefficient was used to determine correlation. The sensitivity, specificity, positive predictive values and negative predictive values were used to get the optimal cut-off values. The diagnostic accuracy was estimated by calculating the area under the Receiver Operating Characteristic Curve (ROC). P Results: Of the 243 patient records studied, the median age or interquartile range (IQR) was 35 (29 - 42) years with a male predominance of 73.7%. More than 60% of the study population had normal transaminases. Significant fibrosis was found in 88 (36.2%) patients and 32 (13.7%) patients had cirrhosis. APRI had the best cut-off values and highest area under the ROC Curve, for significant fibrosis and cirrhosis with 0.55 (0.823 95% CI [0.769 - 0.869], P Conclusion: APRI, had the best diagnostic properties to detect liver fibrosis and cirrhosis in patients with Chronic Hepatitis B in Douala. The cut-off values are 0.55 and 0.65 for significant fibrosis and cirrhosis respectively.展开更多
Cardiovascular disease(CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus,who have a risk of cardiovascular mortality two to four times that of people without diabetes.An indivi...Cardiovascular disease(CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus,who have a risk of cardiovascular mortality two to four times that of people without diabetes.An individualised approach to cardiovascular risk estimation and management is needed.Over the past decades,many risk scores have been developed to predict CVD.However,few have been externally validated in a diabetic population and limited studies have examined the impact of applying a prediction model in clinical practice.Currently,guidelines are focused on testing for CVD in symptomatic patients.Atypical symptoms or silent ischemia are more common in the diabetic population,and with additional markers of vascular disease such as erectile dysfunction and autonomic neuropathy,these guidelines can be difficult to interpret.We propose an algorithm incorporating cardiovascular risk scores in combination with typical and atypical signs and symptoms to alert clinicians to consider further investigation with provocative testing.The modalities for investigation of CVD are discussed.展开更多
Proper diagnosis in the pediatric population is required to eradicate Helicobacter pylori (H. pylori) and prevent gastric cancer. Our aim was to assess the performance of non-invasive tests to diagnose H. pylori infec...Proper diagnosis in the pediatric population is required to eradicate Helicobacter pylori (H. pylori) and prevent gastric cancer. Our aim was to assess the performance of non-invasive tests to diagnose H. pylori infection in pediatric patients. A retrospective analysis was performed on 141 pediatric patients requiring endoscopic evaluation and diagnostic tests for H. pylori infection to define the cause of abdominal symptoms. Non-invasive tests included the 13C-urea breath test (UBT), a monoclonal stool antigen test using enzyme-linked immuno-sorbent assay (mSAT), and a serum immunoglobulin G antibody test using antigens derived from Japanese individuals (S-Ab). This study investigated sensitivity, specificity, likelihood ratios for a positive and a negative test (LR+ and LR-), and accuracy of non-invasive tests, in comparison with invasive tests. Eighty two of 141 patients (58%) were recognized as H. pylori positive by invasive methods. When UBT, mSAT or S-Ab were analyzed, all were found to be effective over 94% accurate. Specificity ranged between 86.7% and 95.8%, and sensitivity ranged between 93.8% and 97.1%. When subjects were stratified into three distinct age groups, the best performance was achieved for 1-6 years old with mSAT at 100% for sensitivity, specificity, and accuracy. S-Ab yielded the best results for children 7-12 years old and the UBT test performed best for 13-18 years old. These results demonstrate the utility of UBT, mSAT, and S-Ab non-invasive tests in diagnosing H. pylori but suggest that certain tests may be optimal for children of distinct ages. Three non-invasive tests, UBT, mSAT and S-Ab showed sufficient sensitivity, specificity and accuracy for the initial diagnosis of H. pylori infection among pediatric patients. Non-invasive tests may contribute to achieving minimum invasive diagnosis with combining with a histological test and a culture test in children.展开更多
BACKGROUND Liver fibrosis leads to liver-related events in patients with chronic hepatitis C(CHC)infection.Although non-invasive tests(NITs)are critical to early detection of the development of liver fibrosis,the prog...BACKGROUND Liver fibrosis leads to liver-related events in patients with chronic hepatitis C(CHC)infection.Although non-invasive tests(NITs)are critical to early detection of the development of liver fibrosis,the prognostic role of NITs remains unclear due to the limited types of NITs and liver outcomes explored in previous studies.AIM To determine the prognostic value of NITs for risk stratification in CHC patients.METHODS The protocol was registered in PROSPERO(International Prospective Register of Systematic Reviews;no.CRD42019128176).The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Search was performed using MEDLINE and EMBASE databases under a timeframe from the inception of the databases through February 25,2020.We restricted our search to CHC cohort studies reporting an association between liver fibrosis assessed by NITs and the development of hepatocellular carcinoma,decompensation,or mortality.Pooled hazard ratios(HR)and area under the receiver operating characteristic(AUROC)for each NIT were estimated using a random effects model.Subgroup analyses were performed for NITs assessed at pre-treatment or post-treatment with sustained virologic response(SVR),treatment with either pegylated interferon and ribavirin or direct acting antiviral,Eastern or Western countries,and different cutoff points.RESULTS The present meta-analysis included 29 cohort studies,enrolling 69339 CHC patients.Fibrosis-4(FIB-4)index,aspartate aminotransferase to platelet ratio(APRI)score,and liver stiffness measurement(LSM)were found to have hepatocellular carcinoma predictive potential with pooled adjusted HRs of 2.48[95%confidence interval(CI):1.91-3.23,I2=96%],4.24(95%CI:2.15-8.38,I2=20%)and 7.90(95%CI:3.98-15.68,I2=52%)and AUROCs of 0.81(95%CI:0.73-0.89,I2=77%),0.81(95%CI:0.75-0.87,I2=68%),and 0.79(95%CI:0.63-0.96,I2=90%),respectively.Pooled adjusted HR with a pre-treatment FIB-4 cutoff of 3.25 was 3.22(95%CI:2.32-4.47,I2=80%).Pooled adjusted HRs for post-treatment with SVR FIB-4,APRI,and LSM were 3.01(95%CI:0.32-28.61,I2=89%),9.88(95%CI:2.21-44.17,I2=24%),and 6.33(95%CI:2.57-15.59,I2=17%),respectively.Pooled adjusted HRs for LSM in patients with SVR following direct acting antiviral therapy was 5.55(95%CI:1.47-21.02,I2=36%).Pooled AUROCs for post-treatment with SVR FIB-4 and LSM were 0.75(95%CI:0.55-0.95,I2=88%)and 0.84(95%CI:0.66-1.03,I2=88%),respectively.Additionally,FIB-4 and LSM were associated with overall mortality,with pooled adjusted HRs of 2.07(95%CI:1.49-2.88,I2=27%)and 4.04(95%CI:2.40-6.80,I2=63%),respectively.CONCLUSION FIB-4,APRI,and LSM showed potential for risk stratification in CHC patients.Cutoff levels need further validation.展开更多
Colorectal cancer(CRC)is a global problem affecting millions of people worldwide.This disease is unique because of its slow progress that makes it preventable and often curable.CRC symptoms usually emerge only at adva...Colorectal cancer(CRC)is a global problem affecting millions of people worldwide.This disease is unique because of its slow progress that makes it preventable and often curable.CRC symptoms usually emerge only at advanced stages of the disease,consequently its early detection can be achieved only through active population screening,which markedly reduces mortality due to this cancer.CRC screening tests that employ non-invasively detectable biomarkers are currently being actively developed and,in most cases,samples of either stool or blood are used.However,alternative biological substances that can be collected non-invasively(colorectal mucus,urine,saliva,exhaled air)have now emerged as new sources of diagnostic biomarkers.The main categories of currently explored CRC biomarkers are:(1)Proteins(comprising widely used haemoglobin);(2)DNA(including mutations and methylation markers);(3)RNA(in particular microRNAs);(4)Low molecular weight metabolites(comprising volatile organic compounds)detectable by metabolomic techniques;and(5)Shifts in gut microbiome composition.Numerous tests for early CRC detection employing such non-invasive biomarkers have been proposed and clinically studied.While some of these studies generated promising early results,very few of the proposed tests have been transformed into clinically validated diagnostic/screening techniques.Such DNA-based tests as Food and Drug Administration-approved multitarget stool test(marketed as Cologuard®)or blood test for methylated septin 9(marketed as Epi proColon®2.0 CE)show good diagnostic performance but remain too expensive and technically complex to become effective CRC screening tools.It can be concluded that,despite its deficiencies,the protein(haemoglobin)detection-based faecal immunochemical test(FIT)today presents the most cost-effective option for non-invasive CRC screening.The combination of non-invasive FIT and confirmatory invasive colonoscopy is the current strategy of choice for CRC screening.However,continuing intense research in the area promises the emergence of new superior non-invasive CRC screening tests that will allow the development of improved disease prevention strategies.展开更多
An association between nonalcoholic fatty liver disease and cardiovascular disease has been repeatedly rep orted. Several studies have focused on levels of gammaglutamyltransferase (GGT) and alanine aminotransferase (...An association between nonalcoholic fatty liver disease and cardiovascular disease has been repeatedly rep orted. Several studies have focused on levels of gammaglutamyltransferase (GGT) and alanine aminotransferase (ALT) in relation to cardiovascular outcomes. Evidence indicates that GGT may have a potential role for cardiovascular risk stratifi cation while the role of ALT for cardiac prognosis remains controversial. A conceptual framework that includes not only GGT and ALT but also markers of hepatocyte apoptosis such as cytokeratin-18 fragments should be developed.展开更多
BACKGROUND Cognitive decline is common among older patients with cardiovascular disease(CVD) and can decrease their self-management abilities. However, the instruments for identifying mild cognitive impairment(MCI) ar...BACKGROUND Cognitive decline is common among older patients with cardiovascular disease(CVD) and can decrease their self-management abilities. However, the instruments for identifying mild cognitive impairment(MCI) are not always feasible in clinical practice. Therefore, this study evaluated whether MCI could be detected using the Japanese version of the Rapid Dementia Screening Test(RDST-J), which is a simple screening tool for identifying cognitive decline.METHODS This retrospective single-center study included patients who were ≥ 65 years old and hospitalized because of CVD.Patients with a pre-hospitalization diagnosis of dementia were excluded. Each patient's cognitive function had been measured at discharge using the RDST-J and the Japanese version of the Montreal Cognitive Assessment(Mo CA-J), which is a standard tool for MCI screening. The correlation between the two scores was evaluated using Spearman's rank correlation coefficient. Receiver operating characteristic(ROC) analysis was also to evaluate whether the RDST-J could identify MCI, which was defined as a Mo CA-J score of ≤ 25 points.RESULTS The study included 78 patients(mean age: 77.2 ± 8.9 years). The RDST-J and Mo CA-J scores were strongly correlated(r = 0.835, P < 0.001). The ROC analysis revealed that an RDST-J score of ≤ 9 points provided 75.4% sensitivity and 95.2% specificity for identifying MCI, with an area under the curve of 0.899(95% CI: 0.835-0.964). The same cut-off value was identified when excluding patients with a high probability of dementia(RDST-J score of ≤ 4 points).CONCLUSIONS The RDST-J may be a simple and effective tool for identifying MCI in older patients with CVD.展开更多
The impact of arterial narrowing/blocking caused by plaque buildup in arteries leads to many life-threatening consequences. This is recognized as a cause in heart attacks and peripheral vascular disease. Diagnosing th...The impact of arterial narrowing/blocking caused by plaque buildup in arteries leads to many life-threatening consequences. This is recognized as a cause in heart attacks and peripheral vascular disease. Diagnosing the illness is only feasible after symptoms have presented to the patient. Currently, the standard for visualizing coronary arteries is through angiography, which may have complications, and impact on the healthcare system. Furthermore, cardiac catheterization may also places high health risks, given its overall invasiveness. Cardiac arrhythmias, infection, and contrast dye nephrotoxicity are recognized complications within this process. Therefore, a noninvasive approach may have potentials to reduce patient complications, finances surrounding healthcare, and more efficient patient care through earlier screening and diagnosing. This research addresses a new approach using photoacoustic (PA) imaging. The transmission properties of atherosclerosis within walls of arteries, can be exploited using photo acoustics, to better visualize and characterize the degree and severity of atherosclerosis. The delivered energy is absorbed by components of the vascular tissue converted into heat, leading to transient thermos elastic expansion, which creates an acoustic emission. The thermal response was analyzed for its fall and recovery times that are attributed to the artery fat type. The control parameters, including the frequency, penetration depth, energy levels, and tissue layer sizes, for multilayered structures were considered. The structures investigated were fatty infiltrate within the artery, blood, bones, and skin, within frequency range from 1 MHz to 3 MHz, and typical tissue sizes in the milli to centimeter range. As high as 14 MPas in the acoustic pressure at 1 MHz, resulted in temperature difference of up to 3.4 K. When the operating frequency was altered to 2 MHz, the temperature changed to 23 K. Furthermore, when the frequency was changed to 3 MHz, the temperature moved to 43 K. The changes in temperatures were for nearly 1 second duration. The results obtained in this study suggest that there is high potential for practical models using flexible substrate with infra-red sensors and acoustic devices.展开更多
Objectives This study aims to assess the impacts of hypertension on health-related quality of life (HRQOL), as well as cardiovascular functional status (CVFS). Methods An instrument was presented based on WHOQOL-BREF ...Objectives This study aims to assess the impacts of hypertension on health-related quality of life (HRQOL), as well as cardiovascular functional status (CVFS). Methods An instrument was presented based on WHOQOL-BREF and SP-16 questionnaire and exercise testing. 57 normotensive and 76 hypertensive subjects aged 35-65 year-old participated the health survey using this instrument. Based on the exercise testing results of the two groups, a discriminate function was established and used to investigate cardiovascular risk factors for hypertensive population. Results The results showed that persons with hypertension rated significantly lower scores on physical health (i.e. limitation in performing daily activities and problems with work or mobility) than did normotensives (P < 0.01). The discriminant score obtained from the exercise testing results was capable of reflecting the impacts of hypertension on CVFS. Conclusions The method presented in this paper provides a more powerful tool to estimate the effects of health interventions and medical therapy for hypertensive population than just self-rated HRQOL questionnaire.展开更多
Rationale: Patients with cancer commonly experience dyspnea originating from ventilatory, circulatory and musculoskeletal sources, and dyspnea is best determined by cardiopulmonary exercise testing (CPET). Objectives:...Rationale: Patients with cancer commonly experience dyspnea originating from ventilatory, circulatory and musculoskeletal sources, and dyspnea is best determined by cardiopulmonary exercise testing (CPET). Objectives: In this retrospective pilot study, we evaluated patients with hematologic and solid malignancies by CPET to determine the primary source of their dyspnea. Methods: Subjects were exercised on a cycle ergometer with increasing workloads. Minute ventilation, heart rate, breathing reserve, oxygen uptake (V’O<sub>2</sub>), O<sub>2</sub>-pulse, ventilatory equivalents for carbon dioxide and oxygen (V’<sub>E</sub>/V’CO<sub>2</sub> and V’<sub>E</sub>/V’O<sub>2</sub>, respectively) were measured at baseline and peak exercise. The slope and intercept for V’<sub>E</sub>/V’CO<sub>2</sub> was computed for all subjects. Peak V’O<sub>2</sub> 4% predicted indicated a circulatory or ventilatory limitation. Results: Complete clinical and physiological data were available for 36 patients (M/F 20/16);32 (89%) exhibited ventilatory or circulatory limitation as shown by a reduced peak V’O<sub>2</sub> and 10 subjects with normal physiologic data. The largest cohort comprised the pulmonary vascular group (n = 18) whose mean ± SD peak V’O<sub>2</sub> was 61% ± 17% predicted. There were close associations between V’O<sub>2</sub> and spirometric values. Peak V’<sub>E</sub>/V’O<sub>2</sub> and V’<sub>E</sub>/V’CO<sub>2</sub> were highest in the circulatory and ventilatory cohorts, consistent with increase in dead space breathing. The intercept of the V’<sub>E</sub>-V’CO<sub>2</sub> relationship was lowest in patients with cardiovascular impairment. Conclusion: Dyspneic patients with malignancies exhibit dead space breathing, many exhibiting a circulatory source for exercise limitation with a prominent pulmonary vascular component. Potential factors include effects of chemo- and radiation therapy on cardiac function and pulmonary vascular endothelium.展开更多
基金Dongguan City Social Development Project(Project number:20161081101023)。
文摘Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.
基金Supported by the 345 Talent Project of Shengjing Hospital,No.M0298.
文摘BACKGROUND Confined placental mosaicism(CPM)is one of the major reasons for discrepancies between the results of non-invasive prenatal testing(NIPT)and fetal karyotype analysis.CASE SUMMARY We encountered a primiparous singleton pregnant woman with a rare CPM consisting of 47,XY,+21;47,XXY;and 46,XY,who obtained a false-positive result on NIPT with a high risk for trisomy 21.Copy-number variation sequencing on amniotic fluid cells,fetal tissue,and placental biopsies showed that the fetal karyotype was 47,XXY,while the placenta was a rare mosaic of 47,XY,+21;47,XXY;and 46,XY.CONCLUSION The patient had a rare CPM consisting of 47,XY,+21;47,XXY;and 46,XY,which caused a discrepancy between the result of NIPT and the actual fetal karyotype.It is important to remember that NIPT is a screening test,not a diagnostic test.Any positive result should be confirmed with invasive testing,and routine ultrasound examination is still necessary after a negative result.
文摘Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorionic villus and amniotic fluid sampling, which result in a significant risk for pregnancy loss. The discovery of cell free fetal DNA circulating in the maternal blood has great potential for the development of non-invasive prenatal testing(NIPT) methodologies. Such strategies have been successfully applied for the determination of the fetal rhesus status and inherited monogenic disease but the field of fetal aneuploidy investigation seems to be more challenging. The main reason for this is that the maternal cell free DNA in the mother's plasma is far more abundant, and because it is identical to half of the corresponding fetal DNA. Approaches developed are mainly based on next generation sequencing(NGS) technologies and epigenetic genetic modifications, such as fetal-maternal DNA differential methylation. At present, genetic services for non-invasive fetal aneuploidy detection are offered using NGS-based approaches but, for reasons that are presented herein, they still serve as screening tests which are not readily accessed by the majority of couples. Here we discuss the limitations of both strategies for NIPT and the future potential of the methods developed.
文摘Hepatocellular carcinoma(HCC)is one of the most common malignancies in the world and it is one of the main complications of cirrhosis and portal hypertension.Even in the presence of a well-established follow-up protocol for cirrhotic patients,to date poor data are available on predictive markers for primary HCC occurrence in the setting of compensated advanced chronic liver disease patients(cACLD).The gold standard method to evaluate the prognosis of patients with cACLD,beyond liver fibrosis assessed with histology,is the measurement of the hepatic venous pressure gradient(HVPG).An HVPG≥10 mmHg has been related to an increased risk of HCC in cACLD patients.However,these methods are burdened by additional costs and risks for patients and are mostly available only in referral centers.In the last decade increasing research has focused on the evaluation of several,simple,non-invasive tests(NITs)as predictors of HCC development.We reviewed the currently available literature on biochemical and ultrasound-based scores developed for the noninvasive evaluation of liver fibrosis and portal hypertension in predicting primary HCC.We found that the most reliable methods to assess HCC risk were the liver stiffness measurement,the aspartate aminotransferase to platelet ratio index score and the fibrosis-4 index.Other promising NITs need further investigations and validation for different liver disease aetiologies.
基金Supported by the Liaoning Provincial Science and Technology Key Project for Translational Medicine,No.2014225020Outstanding Scientific Fund of Shengjing Hospital,No.201102+1 种基金Liaoning Provincial Science and Technology Key Project for Translational Medicine,No.2016509National Science and Technology Major Project,Nos.2017ZX10201201,2017ZX10202202,2017ZX10202203
文摘AIM To explore the effect of alanine aminotransferase(ALT) on the performance of non-invasive fibrosis tests in chronic hepatitis B(CHB) patients. METHODS A total of 599 treatment-naive and biopsy-proven CHB patients were included in the study. The cohort was divided into the following three groups: Normal ALT(ALT ≤ 40), slightly elevated ALT(40 < ALT ≤ 80) and elevated ALT(ALT > 80). The diagnostic performance of five common non-invasive fibrosis tests for liver fibrosis(stages S2-4), including the aspartate aminotransferase(AST)-to-platelet(PLT) ratio index(APRI), fibrosis index based on 4 factors(FIB-4), King's score, Forns index and gamma-glutamyl transpeptidase(GGT)-to-PLT ratio(GPR), were evaluated for each group. RESULTS Higher ALT levels were associated with higher non-invasive fibrosis test scores. Patients with the same fibrosis stage but higher ALT levels showed higher noninvasive test scores. The areas under the receiver operating characteristics curves(AUROCs) of the noninvasive tests for prediction of ≥ S2 were higher for patients with ALT ≤ 40 U/L(range 0.705-0.755) and 40 < ALT ≤ 80 U/L(range 0.726-0.79) than for patients with ALT > 80 U/L(range 0.604-0.701). The AUROCs for predicting ≥ S3 and S4 were higher in patients with ALT ≤ 40 U/L(range 0.736-0.814 for ≥ S3, 0.79-0.833 for S4) than in patients with 40 < ALT ≤ 80 U/L(range 0.732-0.754 for ≥ S3, range 0.626-0.723 for S4) and ALT > 80 U/L(range 0.7-0.784 for ≥ S3, range 0.662-0.719 for S4). The diagnostic accuracy of the non-invasive tests decreased in a stepwise manner with the increase in ALT.CONCLUSION ALT has a significant effect on the diagnostic performance of non-invasive fibrosis tests. The ALT level should be considered before performing these noninvasive tests.
文摘Background: Chronic heart failure is a public health problem worldwide. It has a high mortality rate and is accompanied by a decreased functional capacity and alteration of the quality of life. Objective: This study aimed to assess the cardiovascular functional capacity of a group of patients suffering from heart failure using the 6-minute walk test (6 MWT). Methods: This was a cross-sectional study carried out in the cardiology unit of Douala’s general hospital for 4 months. We included all eligible patients aged 18 years or more who had stable chronic heart failure and gave informed consent. Those who had an acute coronary syndrome (≤1 month), tachycardia (HR ≥ 120 bpm), high blood pressure (SBP ≥ 180 mmHg and/or DBP ≥ 100 mmHg) and reduced mobility due to orthopaedic reasons were excluded. A 6 MWT was done according to the American Thoracic Society guidelines. The 6 MWT result was considered poor for - 450 m and good for >450 m. Results: We recruited a total of 81 patients (61.7% women) with a mean age of 65.9 ± 10.6 years. The most frequent risk factor for heart failure was high blood pressure (77.8%), alcohol consumption(69.1%) and a sedentary lifestyle (53.1%). The left ventricular ejection fraction was mostly preserved (42.0%) or mildly altered (46.9). The 6 MWT results were poor in 55.6% of cases, average in 19.8% of cases and good in only 24.7% of cases. More than half (59.3%) of the participants perceived the effort as being difficult. The cardiovascular functional capacity was significantly associated with age, heart failure stage and physical activity (p Conclusion: Most patients suffering from chronic stable heart failure in the general hospital of Douala have poor cardiovascular functional capacity.
文摘Background: Non-invasive markers which use routine laboratory tests are less expensive and highly needed to assess and stage liver fibrosis in chronic hepatitis B patients in Sub-Saharan Africa. We aimed at evaluating liver fibrosis, using the Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis Index Based on 4 factors (FIB4), and Gamma-glutamyl transpeptidase to Platelet Ratio (GPR) in chronic hepatitis B patients with transient elastography as the reference so as to choose an alternative to transient elastography. Method: We carried out a cross-sectional study using the records of patients who attended the Douala General Hospital and Marie O Polyclinic Douala from 2012 to 2017. Non-invasive tests were compared with Transient Elastography. The Spearman coefficient was used to determine correlation. The sensitivity, specificity, positive predictive values and negative predictive values were used to get the optimal cut-off values. The diagnostic accuracy was estimated by calculating the area under the Receiver Operating Characteristic Curve (ROC). P Results: Of the 243 patient records studied, the median age or interquartile range (IQR) was 35 (29 - 42) years with a male predominance of 73.7%. More than 60% of the study population had normal transaminases. Significant fibrosis was found in 88 (36.2%) patients and 32 (13.7%) patients had cirrhosis. APRI had the best cut-off values and highest area under the ROC Curve, for significant fibrosis and cirrhosis with 0.55 (0.823 95% CI [0.769 - 0.869], P Conclusion: APRI, had the best diagnostic properties to detect liver fibrosis and cirrhosis in patients with Chronic Hepatitis B in Douala. The cut-off values are 0.55 and 0.65 for significant fibrosis and cirrhosis respectively.
文摘Cardiovascular disease(CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus,who have a risk of cardiovascular mortality two to four times that of people without diabetes.An individualised approach to cardiovascular risk estimation and management is needed.Over the past decades,many risk scores have been developed to predict CVD.However,few have been externally validated in a diabetic population and limited studies have examined the impact of applying a prediction model in clinical practice.Currently,guidelines are focused on testing for CVD in symptomatic patients.Atypical symptoms or silent ischemia are more common in the diabetic population,and with additional markers of vascular disease such as erectile dysfunction and autonomic neuropathy,these guidelines can be difficult to interpret.We propose an algorithm incorporating cardiovascular risk scores in combination with typical and atypical signs and symptoms to alert clinicians to consider further investigation with provocative testing.The modalities for investigation of CVD are discussed.
文摘Proper diagnosis in the pediatric population is required to eradicate Helicobacter pylori (H. pylori) and prevent gastric cancer. Our aim was to assess the performance of non-invasive tests to diagnose H. pylori infection in pediatric patients. A retrospective analysis was performed on 141 pediatric patients requiring endoscopic evaluation and diagnostic tests for H. pylori infection to define the cause of abdominal symptoms. Non-invasive tests included the 13C-urea breath test (UBT), a monoclonal stool antigen test using enzyme-linked immuno-sorbent assay (mSAT), and a serum immunoglobulin G antibody test using antigens derived from Japanese individuals (S-Ab). This study investigated sensitivity, specificity, likelihood ratios for a positive and a negative test (LR+ and LR-), and accuracy of non-invasive tests, in comparison with invasive tests. Eighty two of 141 patients (58%) were recognized as H. pylori positive by invasive methods. When UBT, mSAT or S-Ab were analyzed, all were found to be effective over 94% accurate. Specificity ranged between 86.7% and 95.8%, and sensitivity ranged between 93.8% and 97.1%. When subjects were stratified into three distinct age groups, the best performance was achieved for 1-6 years old with mSAT at 100% for sensitivity, specificity, and accuracy. S-Ab yielded the best results for children 7-12 years old and the UBT test performed best for 13-18 years old. These results demonstrate the utility of UBT, mSAT, and S-Ab non-invasive tests in diagnosing H. pylori but suggest that certain tests may be optimal for children of distinct ages. Three non-invasive tests, UBT, mSAT and S-Ab showed sufficient sensitivity, specificity and accuracy for the initial diagnosis of H. pylori infection among pediatric patients. Non-invasive tests may contribute to achieving minimum invasive diagnosis with combining with a histological test and a culture test in children.
基金Supported by Research Grant for New Scholar Ratchadaphiseksomphot Endowment Fund Chulalongkorn University,No.RGN_2559_055_10_30.
文摘BACKGROUND Liver fibrosis leads to liver-related events in patients with chronic hepatitis C(CHC)infection.Although non-invasive tests(NITs)are critical to early detection of the development of liver fibrosis,the prognostic role of NITs remains unclear due to the limited types of NITs and liver outcomes explored in previous studies.AIM To determine the prognostic value of NITs for risk stratification in CHC patients.METHODS The protocol was registered in PROSPERO(International Prospective Register of Systematic Reviews;no.CRD42019128176).The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Search was performed using MEDLINE and EMBASE databases under a timeframe from the inception of the databases through February 25,2020.We restricted our search to CHC cohort studies reporting an association between liver fibrosis assessed by NITs and the development of hepatocellular carcinoma,decompensation,or mortality.Pooled hazard ratios(HR)and area under the receiver operating characteristic(AUROC)for each NIT were estimated using a random effects model.Subgroup analyses were performed for NITs assessed at pre-treatment or post-treatment with sustained virologic response(SVR),treatment with either pegylated interferon and ribavirin or direct acting antiviral,Eastern or Western countries,and different cutoff points.RESULTS The present meta-analysis included 29 cohort studies,enrolling 69339 CHC patients.Fibrosis-4(FIB-4)index,aspartate aminotransferase to platelet ratio(APRI)score,and liver stiffness measurement(LSM)were found to have hepatocellular carcinoma predictive potential with pooled adjusted HRs of 2.48[95%confidence interval(CI):1.91-3.23,I2=96%],4.24(95%CI:2.15-8.38,I2=20%)and 7.90(95%CI:3.98-15.68,I2=52%)and AUROCs of 0.81(95%CI:0.73-0.89,I2=77%),0.81(95%CI:0.75-0.87,I2=68%),and 0.79(95%CI:0.63-0.96,I2=90%),respectively.Pooled adjusted HR with a pre-treatment FIB-4 cutoff of 3.25 was 3.22(95%CI:2.32-4.47,I2=80%).Pooled adjusted HRs for post-treatment with SVR FIB-4,APRI,and LSM were 3.01(95%CI:0.32-28.61,I2=89%),9.88(95%CI:2.21-44.17,I2=24%),and 6.33(95%CI:2.57-15.59,I2=17%),respectively.Pooled adjusted HRs for LSM in patients with SVR following direct acting antiviral therapy was 5.55(95%CI:1.47-21.02,I2=36%).Pooled AUROCs for post-treatment with SVR FIB-4 and LSM were 0.75(95%CI:0.55-0.95,I2=88%)and 0.84(95%CI:0.66-1.03,I2=88%),respectively.Additionally,FIB-4 and LSM were associated with overall mortality,with pooled adjusted HRs of 2.07(95%CI:1.49-2.88,I2=27%)and 4.04(95%CI:2.40-6.80,I2=63%),respectively.CONCLUSION FIB-4,APRI,and LSM showed potential for risk stratification in CHC patients.Cutoff levels need further validation.
文摘Colorectal cancer(CRC)is a global problem affecting millions of people worldwide.This disease is unique because of its slow progress that makes it preventable and often curable.CRC symptoms usually emerge only at advanced stages of the disease,consequently its early detection can be achieved only through active population screening,which markedly reduces mortality due to this cancer.CRC screening tests that employ non-invasively detectable biomarkers are currently being actively developed and,in most cases,samples of either stool or blood are used.However,alternative biological substances that can be collected non-invasively(colorectal mucus,urine,saliva,exhaled air)have now emerged as new sources of diagnostic biomarkers.The main categories of currently explored CRC biomarkers are:(1)Proteins(comprising widely used haemoglobin);(2)DNA(including mutations and methylation markers);(3)RNA(in particular microRNAs);(4)Low molecular weight metabolites(comprising volatile organic compounds)detectable by metabolomic techniques;and(5)Shifts in gut microbiome composition.Numerous tests for early CRC detection employing such non-invasive biomarkers have been proposed and clinically studied.While some of these studies generated promising early results,very few of the proposed tests have been transformed into clinically validated diagnostic/screening techniques.Such DNA-based tests as Food and Drug Administration-approved multitarget stool test(marketed as Cologuard®)or blood test for methylated septin 9(marketed as Epi proColon®2.0 CE)show good diagnostic performance but remain too expensive and technically complex to become effective CRC screening tools.It can be concluded that,despite its deficiencies,the protein(haemoglobin)detection-based faecal immunochemical test(FIT)today presents the most cost-effective option for non-invasive CRC screening.The combination of non-invasive FIT and confirmatory invasive colonoscopy is the current strategy of choice for CRC screening.However,continuing intense research in the area promises the emergence of new superior non-invasive CRC screening tests that will allow the development of improved disease prevention strategies.
文摘An association between nonalcoholic fatty liver disease and cardiovascular disease has been repeatedly rep orted. Several studies have focused on levels of gammaglutamyltransferase (GGT) and alanine aminotransferase (ALT) in relation to cardiovascular outcomes. Evidence indicates that GGT may have a potential role for cardiovascular risk stratifi cation while the role of ALT for cardiac prognosis remains controversial. A conceptual framework that includes not only GGT and ALT but also markers of hepatocyte apoptosis such as cytokeratin-18 fragments should be developed.
文摘BACKGROUND Cognitive decline is common among older patients with cardiovascular disease(CVD) and can decrease their self-management abilities. However, the instruments for identifying mild cognitive impairment(MCI) are not always feasible in clinical practice. Therefore, this study evaluated whether MCI could be detected using the Japanese version of the Rapid Dementia Screening Test(RDST-J), which is a simple screening tool for identifying cognitive decline.METHODS This retrospective single-center study included patients who were ≥ 65 years old and hospitalized because of CVD.Patients with a pre-hospitalization diagnosis of dementia were excluded. Each patient's cognitive function had been measured at discharge using the RDST-J and the Japanese version of the Montreal Cognitive Assessment(Mo CA-J), which is a standard tool for MCI screening. The correlation between the two scores was evaluated using Spearman's rank correlation coefficient. Receiver operating characteristic(ROC) analysis was also to evaluate whether the RDST-J could identify MCI, which was defined as a Mo CA-J score of ≤ 25 points.RESULTS The study included 78 patients(mean age: 77.2 ± 8.9 years). The RDST-J and Mo CA-J scores were strongly correlated(r = 0.835, P < 0.001). The ROC analysis revealed that an RDST-J score of ≤ 9 points provided 75.4% sensitivity and 95.2% specificity for identifying MCI, with an area under the curve of 0.899(95% CI: 0.835-0.964). The same cut-off value was identified when excluding patients with a high probability of dementia(RDST-J score of ≤ 4 points).CONCLUSIONS The RDST-J may be a simple and effective tool for identifying MCI in older patients with CVD.
文摘The impact of arterial narrowing/blocking caused by plaque buildup in arteries leads to many life-threatening consequences. This is recognized as a cause in heart attacks and peripheral vascular disease. Diagnosing the illness is only feasible after symptoms have presented to the patient. Currently, the standard for visualizing coronary arteries is through angiography, which may have complications, and impact on the healthcare system. Furthermore, cardiac catheterization may also places high health risks, given its overall invasiveness. Cardiac arrhythmias, infection, and contrast dye nephrotoxicity are recognized complications within this process. Therefore, a noninvasive approach may have potentials to reduce patient complications, finances surrounding healthcare, and more efficient patient care through earlier screening and diagnosing. This research addresses a new approach using photoacoustic (PA) imaging. The transmission properties of atherosclerosis within walls of arteries, can be exploited using photo acoustics, to better visualize and characterize the degree and severity of atherosclerosis. The delivered energy is absorbed by components of the vascular tissue converted into heat, leading to transient thermos elastic expansion, which creates an acoustic emission. The thermal response was analyzed for its fall and recovery times that are attributed to the artery fat type. The control parameters, including the frequency, penetration depth, energy levels, and tissue layer sizes, for multilayered structures were considered. The structures investigated were fatty infiltrate within the artery, blood, bones, and skin, within frequency range from 1 MHz to 3 MHz, and typical tissue sizes in the milli to centimeter range. As high as 14 MPas in the acoustic pressure at 1 MHz, resulted in temperature difference of up to 3.4 K. When the operating frequency was altered to 2 MHz, the temperature changed to 23 K. Furthermore, when the frequency was changed to 3 MHz, the temperature moved to 43 K. The changes in temperatures were for nearly 1 second duration. The results obtained in this study suggest that there is high potential for practical models using flexible substrate with infra-red sensors and acoustic devices.
文摘Objectives This study aims to assess the impacts of hypertension on health-related quality of life (HRQOL), as well as cardiovascular functional status (CVFS). Methods An instrument was presented based on WHOQOL-BREF and SP-16 questionnaire and exercise testing. 57 normotensive and 76 hypertensive subjects aged 35-65 year-old participated the health survey using this instrument. Based on the exercise testing results of the two groups, a discriminate function was established and used to investigate cardiovascular risk factors for hypertensive population. Results The results showed that persons with hypertension rated significantly lower scores on physical health (i.e. limitation in performing daily activities and problems with work or mobility) than did normotensives (P < 0.01). The discriminant score obtained from the exercise testing results was capable of reflecting the impacts of hypertension on CVFS. Conclusions The method presented in this paper provides a more powerful tool to estimate the effects of health interventions and medical therapy for hypertensive population than just self-rated HRQOL questionnaire.
文摘Rationale: Patients with cancer commonly experience dyspnea originating from ventilatory, circulatory and musculoskeletal sources, and dyspnea is best determined by cardiopulmonary exercise testing (CPET). Objectives: In this retrospective pilot study, we evaluated patients with hematologic and solid malignancies by CPET to determine the primary source of their dyspnea. Methods: Subjects were exercised on a cycle ergometer with increasing workloads. Minute ventilation, heart rate, breathing reserve, oxygen uptake (V’O<sub>2</sub>), O<sub>2</sub>-pulse, ventilatory equivalents for carbon dioxide and oxygen (V’<sub>E</sub>/V’CO<sub>2</sub> and V’<sub>E</sub>/V’O<sub>2</sub>, respectively) were measured at baseline and peak exercise. The slope and intercept for V’<sub>E</sub>/V’CO<sub>2</sub> was computed for all subjects. Peak V’O<sub>2</sub> 4% predicted indicated a circulatory or ventilatory limitation. Results: Complete clinical and physiological data were available for 36 patients (M/F 20/16);32 (89%) exhibited ventilatory or circulatory limitation as shown by a reduced peak V’O<sub>2</sub> and 10 subjects with normal physiologic data. The largest cohort comprised the pulmonary vascular group (n = 18) whose mean ± SD peak V’O<sub>2</sub> was 61% ± 17% predicted. There were close associations between V’O<sub>2</sub> and spirometric values. Peak V’<sub>E</sub>/V’O<sub>2</sub> and V’<sub>E</sub>/V’CO<sub>2</sub> were highest in the circulatory and ventilatory cohorts, consistent with increase in dead space breathing. The intercept of the V’<sub>E</sub>-V’CO<sub>2</sub> relationship was lowest in patients with cardiovascular impairment. Conclusion: Dyspneic patients with malignancies exhibit dead space breathing, many exhibiting a circulatory source for exercise limitation with a prominent pulmonary vascular component. Potential factors include effects of chemo- and radiation therapy on cardiac function and pulmonary vascular endothelium.