Single Noninvasive Test Research Articles

Noninvasive diagnostic modalities and prediction models for detecting pulmonary hypertension associated with interstitial lung disease: a narrative review.

Pulmonary hypertension (PH) is highly prevalent in patients with interstitial lung disease (ILD) and is associated with increased morbidity and mortality. Widely available noninvasive screening tools are warranted to identify patients at risk for PH, especially severe PH, that could be managed at expert centres. This review summarises current evidence on noninvasive diagnostic modalities and prediction models for the timely detection of PH in patients with ILD. It critically evaluates these approaches and discusses future perspectives in the field. A comprehensive literature search was carried out in PubMed and Scopus, identifying 39 articles that fulfilled inclusion criteria. There is currently no single noninvasive test capable of accurately detecting and diagnosing PH in ILD patients. Estimated right ventricular pressure (RVSP) on Doppler echocardiography remains the single most predictive factor of PH, with other indirect echocardiographic markers increasing its diagnostic accuracy. However, RVSP can be difficult to estimate in patients due to suboptimal views from extensive lung disease. The majority of existing composite scores, including variables obtained from chest computed tomography, pulmonary function tests and cardiopulmonary exercise tests, were derived from retrospective studies, whilst lacking validation in external cohorts. Only two available scores, one based on a stepwise echocardiographic approach and the other on functional parameters, predicted the presence of PH with sufficient accuracy and used a validation cohort. Although several methodological limitations prohibit their generalisability, their use may help physicians to detect PH earlier. Further research on the potential of artificial intelligence may guide a more tailored approach, for timely PH diagnosis.

Raman hyperspectroscopy of saliva and machine learning for Sjögren’s disease diagnostics

Sjögren's disease is an autoimmune disorder affecting exocrine glands, causing dry eyes and mouth and other morbidities. Polypharmacy or a history of radiation to the head and neck can also lead to dry mouth. Sjogren's disease is often underdiagnosed due to its non-specific symptoms, limited awareness among healthcare professionals, and the complexity of diagnostic criteria, limiting the ability to provide therapy early. Current diagnostic methods suffer from limitations including the variation in individuals, the absence of a single diagnostic marker, and the low sensitivity and specificity, high cost, complexity, and invasiveness of current procedures. Here we utilized Raman hyperspectroscopy combined with machine learning to develop a novel screening test for Sjögren's disease. The method effectively distinguished Sjögren's disease patients from healthy controls and radiation patients. This technique shows potential for development of a single non-invasive, efficient, rapid, and inexpensive medical screening test for Sjögren's disease using a Raman hyper-spectral signature.

873. Detection of Monkeypox Virus Using Microbial Cell-free DNA: Demonstrating the Potential of Agnostic Sequencing for Real Time Identification of an Emerging Pathogen

Abstract Background The 2022 global monkeypox (mpox) outbreak has resulted in >86,000 cases worldwide. Mpox virus (mpoxv) PCR has failed for some divergent strains. Additionally, currently recommended testing requires a swab of lesions, which arise well after infection and may be unrecognized, especially in atypical disease. We present mpoxv detections using plasma microbial cell-free DNA (mcfDNA) sequencing. Methods We characterized 13 case-patients in whom plasma mcfDNA sequencing, by the Karius CLIA certified/CAP accredited laboratory, detected and quantified the concentration of mpoxv in 16 samples. To confirm mpoxv detections, in-silico experiments were performed to test the inclusivity and exclusivity of the assay. Inclusivity was tested across the mpoxv genomes from the 2022 outbreak; exclusivity was tested to other Poxviridae viruses, some of which may be genetically similar to mpoxv, and other often co-occurring pathogens. In cases of sufficient sequencing coverage, mpoxv isolates were genotyped and phylodynamic information imputed using the nexstrain toolkit. Results Case-patient characteristics at the time of plasma collection for mcfDNA sequencing are shown in Table 1. Mpox was not suspected in 6, with one having documented resolution of mpox >6 mos previously. For those with known mpox, mcfDNA sequencing was performed to determine other co-infections. Seven had moderate to severe mpox disease, supported by high mpoxv mcfDNA concentration; 4 died. Using mcfDNA coverage, 22 mutations were identified at 10 mpoxv genomic loci in 9 case-patients. 21 of the 22 variants were G >A or C >T, consistent with the predominant variation observed in the 2022 mpoxv outbreak. Phylogenetic comparison against public data facilitated mapping case-patient mpoxv strains to specific sublineages arising at different time points and associated with different geographic locations. Conclusion We demonstrate the potential of plasma mcfDNA sequencing to detect, quantify, and subtype mpoxv using a single non-invasive test. This alternative to the current lesion-dependent PCR test may enhance disease surveillance and much needed situational awareness for public health agencies and scientists to track an emerging pathogen with potentially unexpected clinical presentations such as mpoxv. Disclosures Kevin Brick, PhD, Karius: Employee|Karius: Stocks/Bonds Nicholas Noll, Doctor of Philosophy, Karius: Employee Asim Ahmed, MD, Karius: mcfDNA detection of infectious agents|Karius: Stocks/Bonds|Tarsus: Advisor/Consultant Jason Sniffen, DO, MicroGenDX: Advisor/Consultant Gayathri Balasundaram, MSc, Karius Inc: Employee|Karius Inc: Stocks/Bonds Frederick S. Nolte, PhD, Karius: Stocks/Bonds Timothy A. Blauwkamp, PhD, Karius: Board Member|Karius: Ownership Interest Sivan Bercovici, PhD, Karius: Stocks/Bonds

Detection of Mpox Virus Using Microbial Cell-Free DNA: The Potential of Pathogen-Agnostic Sequencing for Rapid Identification of Emerging Pathogens.

The 2022 global outbreak of Monkeypox virus (MPXV) highlighted challenges with polymerase chain reaction detection as divergent strains emerged and atypical presentations limited the applicability of swab sampling. Recommended testing in the United States requires a swab of lesions, which arise late in infection and may be unrecognized. We present MPXV detections using plasma microbial cell-free DNA (mcfDNA) sequencing. Fifteen plasma samples from 12 case-patients were characterized through mcfDNA sequencing. Assay performance was confirmed through in silico inclusivity and exclusivity assessments. MPXV isolates were genotyped using mcfDNA, and phylodynamic information was imputed using publicly available sequences. MPXV mcfDNA was detected in 12 case-patients. Mpox was not suspected in 5, with 1 having documented resolution of mpox >6 months previously. Six had moderate to severe mpox, supported by high MPXV mcfDNA concentrations; 4 died. In 7 case-patients, mcfDNA sequencing detected coinfections. Genotyping by mcfDNA sequencing identified 22 MPXV mutations at 10 genomic loci in 9 case-patients. Consistent with variation observed in the 2022 outbreak, 21 of 22 variants were G > A/C > T. Phylogenetic analyses imputed isolates to sublineages arising at different time points and from different geographic locations. We demonstrate the potential of plasma mcfDNA sequencing to detect, quantify, and, for acute infections with high sequencing coverage, subtype MPXV using a single noninvasive test. Sequencing plasma mcfDNA may augment existing mpox testing in vulnerable patient populations or in patients with atypical symptoms or unrecognized mpox. Strain type information may supplement disease surveillance and facilitate tracking emerging pathogens.

Performance of a blood-based test for the detection of multiple cancer types.

283 Background: Cancers of the esophagus, stomach, pancreas, gallbladder, liver, bile duct, colon and rectum will account for 17% of incident cancer diagnoses and 26% of cancer-related deaths in the US in 2019. We developed a methylation-based cfDNA early multi-cancer detection test that also can predict the tissue of origin (TOO) of these and other cancers types; performance of this test for gastrointestinal (GI) tract cancers is reported here. Methods: The Circulating Cell-free Genome Atlas (CCGA; NCT02889978) study is a prospective, multi-center, observational, case-control study with longitudinal follow-up, enrolling individuals with cancer ( > 20 cancers, all stages, newly diagnosed) and without cancer. Plasma cfDNA was subjected to a cross-validated targeted methylation (TM) sequencing assay. Methylation fragments were combined across targeted genomic regions and assigned a probability of cancer and a predicted TOO. GI cancer classes were upper GI (esophagus/stomach, n = 67), pancreas/gallbladder/extrahepatic bile duct (n = 95), liver/intrahepatic bile duct (n = 29), and colon/rectum (n = 121). Results: Detection across all GI cancers was 82% (95% CI 77-86) at a > 99% pre-set specificity. Overall predicted TOO accuracy was 92% (88-95) among the samples for which TOO was predicted (6/255 had indeterminate predicted TOO). The table shows performance by GI cancer type. Conclusions: Simultaneous detection at high specificity ( > 99%) of multiple cancer types, including GI cancers across stages at high sensitivity (82%), was shown using TM analysis of cfDNA. Accurate (92%) localization of cancers to specific regions of the GI tract was also achieved. Detection of multiple GI cancers from a single noninvasive blood test could be a practical method for detecting GI and other cancers, and may facilitate diagnostic work-ups. Clinical trial information: NCT02889978. [Table: see text]

Coronary CT Angiography-derived Fractional Flow Reserve.

Invasive coronary angiography (ICA) with measurement of fractional flow reserve (FFR) by means of a pressure wire technique is the established reference standard for the functional assessment of coronary artery disease (CAD) ( 1 , 2 ). Coronary computed tomographic (CT) angiography has emerged as a noninvasive method for direct assessment of CAD and plaque characterization with high diagnostic accuracy compared with ICA ( 3 , 4 ). However, the solely anatomic assessment provided with both coronary CT angiography and ICA has poor discriminatory power for ischemia-inducing lesions. FFR derived from standard coronary CT angiography (FFRCT) data sets by using any of several advanced computational analytic approaches enables combined anatomic and hemodynamic assessment of a coronary lesion by a single noninvasive test. Current technical approaches to the calculation of FFRCT include algorithms based on full- and reduced-order computational fluid dynamic modeling, as well as artificial intelligence deep machine learning ( 5 , 6 ). A growing body of evidence has validated the diagnostic accuracy of FFRCT techniques compared with invasive FFR. Improved therapeutic guidance has been demonstrated, showing the potential of FFRCT to streamline and rationalize the care of patients suspected of having CAD and improve outcomes while reducing overall health care costs ( 7 , 8 ). The purpose of this review is to describe the scientific principles, clinical validation, and implementation of various FFRCT approaches, their precursors, and related imaging tests. © RSNA, 2017.

Anatomy and Physiology in a Single Non-invasive Test: CTA-derived FFR

With the development and continued technological advances in regard to computed tomography (CT) platforms, cardiac computed tomography (cCTA) has demonstrated the ability to rapidly and accurately evaluate the coronary arteries for luminal stenosis. However, its strength rests in its negative predictive value. More recently, the application of computational fluid dynamics to standard cCTA datasets has allowed for the calculation of non-invasive fractional flow reserve (FFRCT). Several large prospective trials utilizing FFRCT (HeartFlow, Inc., Redwood City, CA) have demonstrated good correlation between CT-derived FFR when compared to invasive FFR. Additionally a smaller trial utilizing a reduced-order algorithm cFFR (Siemens Healthcare, Forchheim, Germany) also yielded good results when compared to invasive FFR measurements. The application of computational fluid dynamics to standard cCTA datasets has allowed for non-invasive derivation of lesion-specific FFR measurements. This has the ability to increase the specificity and positive predictive value of cCTA.

Diagnostic Evaluation of Neonatal Cholestasis: HIDA Scan and Alagille Criteria.

Dear Editor, Neonatal cholestasis (NC) is defined as prolonged elevation of serum levels of conjugated bilirubin beyond two weeks of life. The two most common causes of NC are biliary atresia (BA) and idiopathic neonatal hepatitis (INH). Early and accurate differentiation of these two entities is very important and determines the prognosis and curability of cholestasis. BA requires surgical intervention as soon as possible; whereas, INH needs medical management (1-3). There is no single non-invasive test that can definitely differentiate these two entities. The gold standard for the diagnosis of BA is intraoperative cholangiography. Liver biopsy is the investigation with high diagnostic usefulness in NC. Its diagnostic accuracy for NC has been more than 90% in several studies (1, 4-6). Alagille identified four clinical features that, although nonspecific, supported the correct diagnosis of intrahepatic or extrahepatic cholestasis in 82% of the cases. These clinical variables included stool color within 10 days of admission, age at onset of acholic stools, birth weight, and the features of hepatic involvement, specifically the presence of hepatomegaly and consistency of the liver in palpation (6). We conducted a retrospective study between March 1996 and March 2007 to review medical records of infants with NC. Patients were all admitted in Children’s Hospital Medical Center affiliated to Tehran University of Medical Sciences, which is the major tertiary pediatric referral center in Iran. We reviewed medical records of 250 infants with NC. Infants were excluded if they did not have liver biopsy results, definite diagnosis or complete data on their medical records. Ultimately, 88 infants with BA confirmed by exploratory laparotomy or INH confirmed by liver biopsy were enrolled into the study. In this study, the gold standard tests were liver biopsy and exploratory laparotomy in INH and BA cases, respectively. The sensitivity, specificity and predictive values of HIDA scan and Alagille criteria were evaluated in comparison with liver biopsy and surgical findings. Chi-square test was used for comparison and P < 0.05 was taken as significant. There were 88 infants with NC, including 49 (55.7%) boys and 39 (44.3%) girls. Of these, 63 (37 boys, 26 girls) were diagnosed to have INH and the remaining 25 (12 boys, 13 girls) had BA, according to liver biopsy (P = 0.361). Laparotomy confirmed liver biopsy results in all 25 cases of BA. It means that liver biopsy had 100% accuracy in diagnosing BA. Thirty-three patients had HIDA scan. Among the 23 cases with a positive scan for BA (Figure 1), 14 of them also had BA in liver biopsy (P = 0.031). Among 15 patients with a positive liver biopsy for INH, HIDA scan had shown INH in only two cases (P = 0.15). Figure 1. HIDA scan report of a patient with biliary atresia Among 18 cases who had all four criteria of Alagille accommodated with INH, 14 (77.8%) cases had INH in liver biopsy (P = 0.0514). Of the five patients who had all four Alagille criteria accommodated with BA, in two (40%) cases, liver biopsy showed BA (P = 0.554). So the accuracy of Alagille criteria in our study is lower than what is reported in the pediatric GI textbooks. HIDA scan had a diagnostic accuracy of 60% and 11% for BA and INH, respectively. In conclusion, there is not a single imaging test or clinical feature that has sufficient sensitivity and specificity to differentiate BA from INH, but according to our study hepatobiliary scintigraphy had a good sensitivity for diagnosing BA and the presence of acholic stools and hepatomegaly is significantly higher in infants with BA. So, scintigraphy and clinical features can help in the assessment of any infant with NC to arrive at a timely diagnosis for appropriate management. Since percutaneous liver biopsy is highly accurate in diagnosing BA, in developing countries such our country, using this modality is cost-effective, and it can preclude unnecessary surgical exploration.

Myocardial Perfusion Imaging with Cardiac Computed Tomography: State of the Art

Cardiac computed tomography (CCT) has become an important tool for the anatomic assessment of patients with suspected coronary disease. Its diagnostic accuracy for detecting the presence of underlying coronary artery disease and ability to risk stratify patients are well documented. However, the role of CCT for the physiologic assessment of myocardial perfusion during resting and stress conditions is only now emerging. With the addition of myocardial perfusion imaging to coronary imaging, CCT has the potential to assess both coronary anatomy and its functional significance with a single non-invasive test. In this review, we discuss the current state of CCT myocardial perfusion imaging for the detection of myocardial ischemia and myocardial infarction and examine its complementary role to CCT coronary imaging.

Computed Fractional Flow Reserve (FFTCT) Derived from Coronary CT Angiography

Recent advances in image-based modeling and computational fluid dynamics permit the calculation of coronary artery pressure and flow from typically acquired coronary computed tomography (CT) scans. Computed fractional flow reserve is the ratio of mean coronary artery pressure divided by mean aortic pressure under conditions of simulated maximal coronary hyperemia, thus providing a noninvasive estimate of fractional flow reserve (FFRCT) at every point in the coronary tree. Prospective multicenter clinical trials have shown that computed FFRCT improves diagnostic accuracy and discrimination compared to CT stenosis alone for the diagnosis of hemodynamically significant coronary artery disease (CAD), when compared to invasive FFR as the reference gold standard. This promising new technology provides a combined anatomic and physiologic assessment of CAD in a single noninvasive test that can help select patients for invasive angiography and revascularization or best medical therapy. Further evaluation of the clinical effectiveness and economic implications of noninvasive FFRCT are now being explored.

Visualization of rodent brain tumor angiogenesis and effects of antiangiogenic treatment using 3D ΔR2-μMRA

Understanding of structural and functional characteristics of the vascular microenvironment in gliomas and the impact of antiangiogenic treatments is essential for developing better therapeutic strategies. Although a number of methods exist in which this process can be studied experimentally, no single noninvasive test has the capacity to provide information concerning both microvascular function and morphology. The purpose of present study is to demonstrate the feasibility of using a novel three-dimensional ΔR2-based microscopic magnetic resonance angiography (3D ΔR2-μMRA) technique for longitudinal imaging of tumor angiogenesis and monitoring the effects of antiangiogenic treatment in rodent brain tumor models. Using 3D ΔR2-μMRA, a generally consistent early pattern of vascular development in gliomas was revealed, in which a single feeding vessel was visualized first (arteriogenesis), followed by sprouting angiogenesis. Considerable variability of the tumor-associated vasculature was then noted at later stages of tumor evolution. ΔR2-μMRA revealed that anti-vascular endothelial growth factor treatment induced a rapid and significant alteration of the intratumoral angiogenic phenotype. In summary, 3D ΔR2-μMRA enables high-resolution visualization of tumor-associated vessels while simultaneously providing functional information on the tumor microvasculature. It can serve as a useful tool for monitoring both the temporal evolution of tumor angiogenesis and the impact of antiangiogenic therapies.

“One-stop-shop” cardiac MRI at 3.0T for the detection of coronary artery disease

We present one-stop-shop cardiac MRI findings in a 58-year-old male patient with suspected coronary artery disease (CAD) who was scheduled for a primary diagnostic invasive coronary angiography. The patient was instructed to refrain from any beverage or foods containing caffeine, and antianginal medication within 24 hours before the MRI study. The study was performed on a 3.0T whole-body clinical scanner (MAGNETOM Tim Trio, Siemens Healthcare, Erlangen, Germany) equipped with a 12-element cardiac coil. The one-stop-shop cardiac MRI procedure consisted of four major protocols performed in the following order: 1) cine imaging for assessment of left ventricular function; 2) adenosine gadolinium first-pass imaging for assessment of stress perfusion; 3) coronary MRA for assessment of coronary artery anatomy; and 4) delayed enhancement MRI for assessment of myocardial infarction. After localizer sequences, a FLASH sequence was used for cine imaging. The following sequence parameters were used: TR/TE/flip-angle = 5.00 ms/2.44 ms/13°. The short-axis views were distributed to cover the entire left ventricle and two long-axis views (four- and two-chamber views) were also acquired. Adenosine was then administered intravenously at 140 µg/kg/min with the heart rate and blood pressure monitored. After 3 min of the adenosine infusion, an intravenous bolus injection of 0.05 mmol/kg gadolinium contrast material (Magnevist, Schering, Berlin, Germany) was administered into an antecubital vein on the opposing arm with the use of a power injector (Spectris, Medrad, Indianola, Pennsylvania) at a rate of 4 ml/s, followed by a 20 ml saline flush at 4 ml/s. A SR-Turbo-FLASH sequence was used for perfusion imaging with the following parameters: TR/TE/flip-angle = 2.38/1.14/12°, FOV = 270×360 mm2, matrix = 94×192, spatial resolution = 2.9×1.9×10 mm3, GRAPPA factor = 2, TI = 100 ms, and the number of slices = 3. Whole-heart coronary MRA with additional slow infusion of contrast material (0.15 mmol/kg at 0.3 ml/sec) was acquired after perfusion imaging. A navigator-gated, electrocardiography-triggered, fat saturated, segmented 3D fast low-angle shot sequence [1,2], with the following image parameters was used: TR/TE/flip-angle = 3.0/1.4/20°, readout bandwidth = 610 Hz/pixel, voxel size = 1.3 × 1.3 × 1.3 mm3 interpolated to 0.65 × 0.65 × 0.65 mm3, GRAPPA factor = 2, inversion prepulse delay = 200 ms. Delayed enhancement images were acquired by phase sensitive inversion recovery sequences after coronary MRA for viability study. The total examination time was 33 min. Acquisition time of whole-heart coronary MRA procedure was 9.1 min with a navigator acceptance rate of 34%. Data reformation and analysis were performed on a commercially available workstation (Leonardo, Siemens Healthcare, Erlangen, Germany). Figure 1 shows “one-stop-shop” cardiac MRI images at 3.0T from the 58-year-old male patient with suspected CAD. Figure 1 “One-stop-shop” cardiac MRI images at 3.0T from a 58-year-old male patient with suspected CAD. Perfusion image (A) demonstrates perfusion defects in the mid anteroseptal and inferoseptal segments. Coronary MRA images (B and C) show significant ... This work shows the feasibility of a comprehensive protocol one-stop-shop for cardiac MRI at 3.0T. It is possible to complete the cine imaging, perfusion imaging, coronary MRA, and delayed enhancement imaging in a single study within 35 minutes. The major advantage of this approach is that it offers functional studies for the detection of ischemia, tissue characterization for the detection and quantification of myocardial infarction as well as luminal assessment of the coronary arteries in a single noninvasive and radiation free test. This may be extremely useful for better selecting patients to undergo an invasive procedure. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [3].

Utility of CMR in identification of post lung transplant cardiovascular complications

Background Graft dysfunction after lung transplantation is typically attributable to infection or rejection. In the absence of these entities, structural cardiovascular (CV) abnormalities need to be sought. At our center this evaluation typically includes a myriad of diagnostic tests: echocardiography, chest computed tomographic angiography, nuclear medicine lung perfusion imaging, and right heart catheterization (RHC). This study was designed to evaluate the utility of a novel comprehensive CMR protocol for identification of all post-operative structural CV complications in lung transplant recipients. Methods We enrolled 80 consecutive lung transplant recipients who were referred for CMR evaluation of CV abnormalities. There were 47 men and 33 women; mean age 56.7 ±13.6 years; 55 Caucasians, 9 Hispanic, 13 African American, and 3 Asian. Underlying restrictive disease was present in 39 subjects, obstructive disorders in 22, and other disorders in 19. Forty-three subjects had undergone double lung transplant, while 37 subjects had single lung transplant (23 left lung, and 14 right lung). The comprehensive CMR protocol included complete short and long axis cine imaging (SSFP) to evaluate cardiac size and function; ECG gated spin echo imaging to assess pericardial thickness; contrast enhanced MRA of the pulmonary arterial (PA) and venous (PV) systems to assess for anastomotic site stenosis; phase contrast velocity flow mapping to assess anastomotic site peak velocity and right and left PA flow fraction; and inversion recovery SSFP to evaluate for myocardial fibrosis. Results All 80 subjects completed CMR imaging without difficulty and none were excluded from this analysis for reasons of image quality. The mean LVEF was 66.4±9.23%, mean RVEF was 54.37±10.45%, right and left PAs flow were 2.6±1.21 and 2.6± 1.31 liter/min, respectively. Specific complications identified and the prevalence is shown in Table 1. Patients with moderate or severe PA or PV anastomotic site stenosis underwent RHC and intravascular ultrasound, which confirmed CMR findings; patients with severe stenosis underwent stenting of the respective vessel. Patients with CMR evidence of pericardial constriction underwent pericardiectomy with improvement in symptoms. Conclusions A comprehensive CMR protocol can be a useful single noninvasive test for the detection of structural cardiovascular (CV) abnormalities after lung transplantation. Funding Not applicable.

Helicobacter pylori infection in children

Helicobacter pylori infection is mainly acquired during childhood period. It is recognised as a cause of gastritis and peptic ulcer and it has been classified as a group A carcinogen by the World Health Organisation. There is emerging evidence in different populations including developing countries that the prevalence of H.pylori is declining in all age groups. Neither the treatment of the infection nor improvement in socioeconomic factors fully explains the decline. Most of the infected children are asymtomatic, and there is no specific clinical picture indicating a need to screen for H. pylori in pediatric age groups. Although there is abundance of invasive and non-invasive tests for the diagnosis of the infection, there is still no single noninvasive diagnostic test for the diagnosis of H.pylori in children, particularly in infants. Additionally, the real outcome of the infecion in children is still obscure. The scope of this review was to discuss the epidemiology, clinical features, diagnostic techniques, and management of H.pylori infection pediatric paitents.

Idiopathic pulmonary fibrosis‐related pulmonary hypertension; an exercising diagnosis?

Idiopathic pulmonary fibrosis‐related pulmonary hypertension; an exercising diagnosis?

Systematic review: non‐invasive methods of fibrosis analysis in chronic hepatitis C

Accurate determination of the presence and degree of liver fibrosis is essential for prognosis and for planning treatment of patients with chronic hepatitis C virus (HCV). Non-invasive methods of assessing fibrosis have been developed to reduce the need for biopsy. To perform a review of these non-invasive measures and their ability to replace biopsy for assessing hepatic fibrosis in patients with chronic HCV. A systematic review of PUBMED and EMBASE was performed through 2008 using the following search terms: HCV, liver, elastography, hepatitis, Fibroscan, SPECT, noninvasive liver fibrosis, ultrasonography, Doppler, MRI, Fibrotest, Fibrosure, Actitest, APRI, Forns and breath tests, alone or in combination. We identified 151 studies: 87 using biochemical, 57 imaging and seven breath tests either alone or in combination. Great strides are being made in the development of accurate non-invasive methods for determination of fibrosis. Although no single non-invasive test or model developed to date can match that information obtained from actual histology (i.e. inflammation, fibrosis, steatosis), combinations of two modalities of non-invasive methods can reliably differentiate between minimal and significant fibrosis, and thereby avoid liver biopsy in a significant percentage of patients.

Subsegmental Pulmonary Embolism: Value of Thoracic Ultrasound for Diagnosis and Follow-Up

Timely diagnosis of pulmonary embolism (PE) is crucial because prompt appropriate management can decrease mortality and morbidity. However, the diagnosis of PE is often a challenge because of aspecific clinical presentation and the lack of a single non-invasive diagnostic test sufficiently sensitive for the diagnosis in all suspected cases. The present report describes a 37-year-old woman in whom diagnosis of recurrent subsegmental PE was achieved through subtle integration of imaging techniques including thoracic ultrasound (TUS) that was demonstrated to be of valuable usefulness. We think that TUS may represent an adjunctive technique for diagnosing PE.

When to perform CTA in patients suspected of PE?

Venous thromboembolic disease (VTE) is a common disorder which may be associated with high morbidity or mortality when left untreated. Specific VTE diagnosis is mandatory, as treatment is associated with significant side effects. Therefore, timely diagnostic tests are necessary to establish the presence or absence of VTE. Computed tomographic pulmonary angiography (CTPA) has reached a high accuracy in the evaluation of pulmonary embolism (PE). Unfortunately, the continuous decrease of the prevalence of PE in the most recent studies can lead to cost-efficacy imbalance and overuse of ionizing radiation when CTPA is used as a single test. Therefore, no single non-invasive test is suitable for all patients and diagnostic strategies based on sequential non-invasive tests are likely to identify patients in whom anticoagulation can be withheld safely and limit the number of patients requiring more invasive or more expensive tests. The cost effectiveness of clinical stratification and D-dimer test has been demonstrated as it reduces the requirement for invasive tests. In this paper, the current role of CTPA in the diagnosis of PE will be reviewed.

Ultrasound Diagnosis of Ectopic Pregnancy

The diagnosis of tubal ectopic pregnancy should be based upon the positive visualization of an adnexal mass using transvaginal ultrasound rather than the absence of an intrauterine gestational sac. Ultrasound diagnosis earlier in the natural history of the condition has meant that more conservative treatment options can be considered and implemented in clinically stable women. Although laparoscopy traditionally is accepted as the gold standard in the diagnosis of tubal ectopic pregnancy, there is substantial evidence that transvaginal ultrasound is the diagnostic tool of choice in modern practice. In expert hands, this single noninvasive and reproducible diagnostic test correlates well with the presence of ectopic pregnancy at the time of surgery. This article discusses the use of ultrasound as a single stand-alone test in the diagnosis of tubal ectopic pregnancy.

Diagnosis of Pulmonary Embolism

Conventional pulmonary arteriography for the diagnosis of pulmonary embolism (PE) bears several limitations in clinical practice, basically due to its invasiveness. On the other hand, no single noninvasive test is both sensitive and specific for the diagnosis of PE. Therefore, the choice of available noninvasive diagnostic tests guided by the clinical probability of PE is a good compromise at present. The first necessary step toward the diagnosis of PE is to raise the clinical suspicion, given that no diagnosis can be made if PE is not considered in the differential diagnosis of patients with acute cardiorespiratory symptoms. Second, empirical or standardized rules for predicting clinical probability may be combined with one or more noninvasive tests with the aim of increasing the accuracy of the noninvasive diagnosis. The strategy for the noninvasive diagnosis of PE varies among different centers according to the availability of each single technique that may be integrated with another and according to the characteristics of the population that refers to each single center. Therefore, spiral CT should not be used as a primary tool for the diagnosis of PE; its role needs to be re-evaluated in light of its sensitivity, feasibility, and radiation burden on the patients. In patients in whom the diagnosis of PE cannot be made at the end of the noninvasive pathway, the use of the invasive techniques must be taken into consideration. In our experience, however, such cases should not exceed 15 to 20% of the total patient population.