Diagnostic Yield In Patients Research Articles

Timing of cardiovascular magnetic resonance imaging and diagnostic yield in patients with acute myocardial infarction with nonobstructive coronary arteries

Abstract Background Accurate diagnosis of the underlying cause of myocardial infarction (MI) without obstructive coronary artery disease (MINOCA) is crucial. Cardiovascular magnetic resonance (CMR) plays an important role in the work up of patients with MINOCA. However, the timing of performance of CMR may impact on the diagnosis yield. Purpose To establish the diagnostic yield of CMR in a large cohort of patients admitted with MINOCA based on the timing of referral to CMR. Methods All patients referred to CMR from January 2009 to February 2022 with MINOCA were included. Studies were performed on a 1.5 T or 3T scanners. SSFP cines, T2-weighted black-blood fat-sat images and DE-segmented GE IR images 10–15 minutes after iv gadolinium-DTPA administration (0.15mmol/kg) were performed in 3 long-axis and 11–15 parallel short-axis views. All images were reviewed and analyzed off-line with specialized post-processing software. Results A total of 203 patients (median age 49 years, 60% men) with MINOCA diagnosis were included. Main ECG alterations were ST-segment elevation (STE) (57%) and T wave inversion (19%). Mean peak high sensitivity (HS)-TnI levels were 3706pg/mL. Median time to CMR was 7 days (5–9 days). Mean LVEF was 58% (range 18–83%) and mean LVEDVi 77 mL/m2 (range 35–210 mL/m2). Regional wall abnormalities were present in 123 patients (62%). High signal in T2w images was detected in 153 cases (75%) and late gadolinium enhancement (LGE) in 143cases (71%). Final CMR diagnosis resulted in myocarditis in 46%, MI in 20%, Takotsubo in 18%, and other cardiomyopathies in 6.4%. CMR was normal in 15 patients and not conclusive in 1. When CMR was performed within 7 days of admission (median: 5 days (4–6 days); n: 116 patients), the distribution of diagnoses was myocarditis in 53%, MI in 20%, Takotsubo in 16%, other cardiomyopathies in 6% and normal CMR in 4%. Whereas, if CMR was performed after 7 days (median: 10 days (8–12 days); n: 87 patients), the diagnoses were as flows: myocarditis in 36%, MI in 22%, Takotsubo 20%, cardiomyopathies in 7%, not conclusive in 1% and normal CMR in 13% (Table 1). Conclusions CMR led to the underlying diagnosis of MINOCA in 92% of patients. Myocarditis was the most frequent diagnosis. The final diagnosis of myocarditis was more frequent when CMR was performed within 7 days with a lesser percentage of normal CMR. Funding Acknowledgement Type of funding sources: None.

META ANALYSIS OF DIAGNOSTIC YIELD AND COMPLICATIONS WITH ROBOTIC-ASSISTED NAVIGATION BRONCHOSCOPY

META ANALYSIS OF DIAGNOSTIC YIELD AND COMPLICATIONS WITH ROBOTIC-ASSISTED NAVIGATION BRONCHOSCOPY

S46 EUS-Guided Through the Needle Biopsy vs Fine Needle Aspiration for Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis

Introduction: Endoscopic Ultrasound guided fine needle aspiration (EUS-FNA) has been widely used to collect samples from pancreatic cystic lesions (PCLs) for cytology and fluid analysis. However, EUS guided FNA has relatively lower sensitivity in discriminating the types of lesions as well as detection of malignancy. Recent studies have investigated the EUS guided through the needle biopsy (EUS-TTNB) as an alternative method for sample collections in PCLs. We conducted a systemic review and meta-analysis on the studies that compared EUS-FNA and EUS-TTNB for adequate sampling and diagnostic accuracy in patients with PCLs. Methods: We performed a comprehensive search of the databases: PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception through May 10th, 2022. We considered randomized controlled trials, cohort studies, and case-control studies. We excluded abstracts, animal studies, case reports, reviews, editorials, and letters to editors. The primary outcome was sample adequacy which is defined as the presence of enough sample for histopathological evaluation. The secondary outcome was sample accuracy which is defined as the ability to have a definite diagnosis. The random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). A p value < 0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I2 index. Results: Nine observational studies involving 520 patients were included in the meta-analysis. The rate of sample adequacy was significantly higher in the EUS-TTNB group compared to the EUS-FNA group (RR 1.64, 95% CI 1.19-2.26, p =0.003, I2 = 95%) (Figure 1A). Only four studies compared the accuracy rate between the EUS-TTNB method and the EUS-FNA group. The diagnostic accuracy was significantly higher in the EUS-TTNB group compared to the EUS-FNA group (RR 2.03, 95% CI 1.13-3.65, p = 0.02, I2 = 87%) (Figure 1B). Conclusion: Our meta-analysis demonstrated that the rates of both sample adequacy and accuracy were higher in the EUS-TTNB group compared to the EUS-FNA group. EUS-TTNB should be considered where applicable clinically for improving the diagnostic yield in patients undergoing evaluation of PCLs. Further randomized controlled trials are needed to confirm our findings.Figure 1.: a) sample adequacy rate b) diagnostic accuracy rate

Genetics of Pediatric Epilepsy: Next-Generation Sequencing in Clinical Practice.

Epilepsy is one of the most common neurological disorders with diverse phenotypic characteristics and high genetic heterogeneity. Epilepsy often occurs in childhood, so timely diagnosis and adequate therapy are crucial for preserving quality of life and unhindered development of a child. Next-generation-sequencing (NGS)-based tools have shown potential in increasing diagnostic yield. The primary objective of this study was to evaluate the impact of genetic testing and to investigate the diagnostic utility of targeted gene panel sequencing. This retrospective cohort study included 277 patients aged 6 months to 17 years undergoing NGS with an epilepsy panel covering 142 genes. Of 118 variants detected, 38 (32.2%) were not described in the literature. We identified 64 pathogenic or likely pathogenic variants with an overall diagnostic yield of 23.1%. We showed a significantly higher diagnostic yield in patients with developmental delay (28.9%). Furthermore, we showed that patients with variants reported as pathogenic presented with seizures at a younger age, which led to the conclusion that such children should be included in genomic diagnostic procedures as soon as possible to achieve a correct diagnosis in a timely manner, potentially leading to better treatment and avoidance of unnecessary procedures. Describing and discovering the genetic background of the disease not only leads to a better understanding of the mechanisms of the disorder but also opens the possibility of more precise and individualized treatment based on stratified medicine.

The Usefulness of a Targeted Next Generation Sequencing Gene Panel in Providing Molecular Diagnosis to Patients With a Broad Spectrum of Neurodevelopmental Disorders.

Background: Neurodevelopmental disorders comprise a clinically and genetically heterogeneous group of conditions that affect 2%–5% of children and represents a public health challenge due to complexity of the etiology. Only few patients with unexplained syndromic and non-syndromic NDDs receive a diagnosis through first-tier genetic tests as array-CGH and the search for FMR1 CGG expansion. The aim of this study was to evaluate the clinical performance of a targeted next-generation sequencing (NGS) gene panel as a second-tier test in a group of undiagnosed patients with NDDs. Method: A 221-gene next-generation sequencing custom panel was designed and used to analyze a cohort of 338 patients with a broad spectrum of NDDs (202 males and 136 females) including Intellectual Disability (ID), Autism Spectrum Disorders (ASD), Epilepsy, language and motor disorders. Results: A molecular diagnosis was established in 71 patients (21%) and a de novo origin was present in 38 (64.4%) of the available trios. The diagnostic yield was significantly higher in females than in males (29.4% vs. 15.3%; p = 0.0019) in particular in ASD (36.8% vs. 7.6%; p = 0.0026) and Epilepsy (38.9% vs. 14.4% p = 0.001). The most involved genes were SLC2A1, SCN1A, ANKRD11, ATP1A2, CACNA1A, FOXP1, and GNAS altered in more than two patients and accounting for the 19.7% of the diagnosis. Conclusion: Our findings showed that this NGS panel represents a powerful and affordable clinical tool, significantly increasing the diagnostic yield in patients with different form of NDDs in a cost- and time-effective manner without the need of large investments in data storage and bioinformatic analysis.

The associations of radiological features of high-resolution computed tomography with the outcomes of transbronchial cryobiopsy in interstitial lung diseases: A cohort study.

BackgroundTransbronchial cryobiopsy (TBCB) is a critical procedure in the diagnosis of interstitial lung diseases (ILD). The associations between high-resolution computed tomography (HRCT) features and outcomes of TBCB were unknown.MethodsThis study was conducted as a single-center prospective cohort study between September 2018 and January 2020 (NCT04047667). HRCT was obtained before performing TBCB. The clinical and radiological characteristics, complications, pathological and multidisciplinary discussion (MDD) diagnoses were recorded. The relationships between HRCT features and outcomes of TBCB were analyzed.ResultsTBCB was performed on 216 ILD patients. The radiological features usually interstitial pneumonia (UIP) or probable UIP, indeterminate for UIP, ground-glass opacities (GGO) and cysts were found in 55 (25.5%), 38 (17.6%), 84 (38.9%) and 9 (4.2%) patients, respectively. And 118 (54.6%) patients had high HRCT score (involved lung proportion ≥50%) in the biopsied lobe. Multivariate analysis suggested radiological probable UIP pattern may be an independent risk factor for moderate bleeding (OR = 4.304; 95% CI: 1.383–13.393; P = 0.012), while GGO may be a protective factor from moderate bleeding (OR = 0.173, 95% CI: 0.043–0.687; P = 0.013). The pathological diagnostic yield in patients presenting cysts on HRCT was significantly lower than others (44.4 vs. 87.9%; P = 0.009). While performing TBCB in the lobe with high HRCT score increased pathological diagnostic yield (91.5 vs. 79.6%; P = 0.022). Neither pneumothorax nor MDD diagnostic yields were found to be associated with HRCT features.ConclusionsHRCT features were associated with moderate bleeding and pathological diagnosis. Pre-TBCB assessments of HRCT pattern and scores were helpful for bronchoscopists to make a better patient selection and procedure planning.

Medical Thoracoscopy for Undiagnosed Pleural Effusions: Experience from a Tertiary Care Hospital in North India

Medical thoracoscopy, also called pleuroscopy, has received renewed interest in the recent past for diagnostic as well as therapeutic uses. In this study, we describe our experience with thoracoscopy for undiagnosed pleural effusions. In a retrospective analysis of thoracoscopic procedures we performed between January 2007 and December 2008, yield of thoracoscopic pleural biopsy for achieving a diagnosis in undiagnosed pleural effusions, defined as pleural effusions with adenosine deaminase (ADA) levels less than 70 IU/L and negative pleural fluid cytology for malignancy on three occasions was evaluated. Complications of thoracoscopy were also analysed. Overall diagnostic yield of thoracoscopic pleural biopsy was 74.3% in patients with undiagnosed pleural effusions. Pleural malignancy was diagnosed in 48.6% of patients. There was only one case of mesothelioma and the rest were due to pleural metastasis. Lung cancer and breast cancer were the most common sites of primary malignancy. Tuberculosis was diagnosed with pleural biopsy in 22.8% of patients. We had low complication rate after thoracoscopy. Only two cases of empyema were observed. Medical thoracoscopy is a safe procedure and has good diagnostic yield in patients with undiagnosed pleural effusions.

First prospective European study for the feasibility and safety of magnetically controlled capsule endoscopy in gastric mucosal abnormalities.

BACKGROUNDWhile capsule endoscopy (CE) is the gold standard diagnostic method of detecting small bowel (SB) diseases and disorders, a novel magnetically controlled capsule endoscopy (MCCE) system provides non-invasive evaluation of the gastric mucosal surface, which can be performed without sedation or discomfort. During standard SBCE, passive movement of the CE may cause areas of the complex anatomy of the gastric mucosa to remain unexplored, whereas the precision of MCCE capsule movements inside the stomach promises better visualization of the entire mucosa.AIMTo evaluate the Ankon MCCE system’s feasibility, safety, and diagnostic yield in patients with gastric or SB disorders.METHODSOf outpatients who were referred for SBCE, 284 (male/female: 149/135) were prospectively enrolled and evaluated by MCCE. The stomach was examined in the supine, left, and right lateral decubitus positions without sedation. Next, all patients underwent a complete SBCE study protocol. The gastric mucosa was explored with the Ankon MCCE system with active magnetic control of the capsule endoscope in the stomach, applying three standardized pre-programmed computerized algorithms in combination with manual control of the magnetic movements.RESULTSThe urea breath test revealed Helicobacter pylori positivity in 32.7% of patients. The mean gastric and SB transit times with MCCE were 0 h 47 min 40 s and 3 h 46 min 22 s, respectively. The average total time of upper gastrointestinal MCCE examination was 5 h 48 min 35 s. Active magnetic movement of the Ankon capsule through the pylorus was successful in 41.9% of patients. Overall diagnostic yield for detecting abnormalities in the stomach and SB was 81.9% (68.6% minor; 13.3% major pathologies); 25.8% of abnormalities were in the SB; 74.2% were in the stomach. The diagnostic yield for stomach/SB was 55.9%/12.7% for minor and 4.9%/8.4% for major pathologies.CONCLUSIONMCCE is a feasible, safe diagnostic method for evaluating gastric mucosal lesions and is a promising non-invasive screening tool to decrease morbidity and mortality in upper gastro-intestinal diseases.

Microdeletions in 1q21 and 8q12.1 depict two additional molecular subgroups of Silver-Russell syndrome like phenotypes

BackgroundSilver-Russell syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction, relative macrocephaly at birth, body asymmetry and typical facial features. Clinical and molecular heterogeneity is described in SRS. Common causes are loss of methylation of the imprinting center 1 in 11p15 and maternal uniparental disomy of chromosome 7. Other genetic alterations include disturbances of imprinted regions in 14q32, 7q32 and 11p15 as well as submicroscopic deletions and duplications. Single nucleotide variants in genes like IGF2, HMGA2, PLAG1, CDKN1C have also been identified in patients with SRS phenotypes. However, routine molecular diagnostics usually focus on 11p15 and chromosome 7, while less frequent causes are not systematically addressed.ResultsHere we report two patients with SRS features in which molecular karyotyping revealed microdeletions in 1q21 and 8q12.1 respectively. In a 3.5-year-old girl with postnatal growth restriction, feeding difficulties, relative macrocephaly and distinct SRS features a 2 Mb deletion in 1q21.1q21.2 was identified. Our second case is a 1.5-year-old boy with intrauterine and postnatal growth restriction, feeding difficulties and distinct facial features with a 77 kb deletion in 8q12.1 affecting PLAG1 as the only protein-encoding gene with known function.ConclusionsThe 1q21 region has not yet been assigned as an SRS region, although six patients with the same deletion and SRS features including relative macrocephaly have been described before. This new case adds to the evidence that distal 1q21 should be annotated as an SRS candidate region. The PLAGL1 alteration is the smallest deletion in 8q12.1 ever reported in a patient with SRS phenotype and it finally confirms that PLAG1 is the SRS causing gene in 8q12.1. To increase the diagnostic yield in patients with suspected SRS, we recommend both molecular karyotyping and next generation sequencing-based approaches.

Diagnostic yield of MR myelography in patients with newly diagnosed spontaneous intracranial hypotension: a systematic review and meta-analysis.

To investigate the pooled diagnostic yield of MR myelography in patients with newly diagnosed spontaneous intracranial hypotension (SIH). A literature search of the MEDLINE/PubMed and Embase databases was conducted until July 25, 2021, including studies with the following inclusion criteria: (a) population: patients with newly diagnosed SIH; (b) diagnostic modality: MR myelography or MR myelography with intrathecal gadolinium for evaluation of CSF leakage; (c) outcomes: diagnostic yield of MR myelography or MR myelography with intrathecal gadolinium. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. DerSimonian-Laird random-effects modeling was used to calculate the pooled estimates. Subgroup analysis regarding epidural fluid collection and meta-regression were additionally performed. Fifteen studies with 643 patients were included. Eight studies used MR myelography with intrathecal gadolinium, and 11 used MR myelography. The overall quality of the included studies was moderate. The pooled diagnostic yield of MR myelography was 86% (95% CI, 80-91%) and that of MR myelography with intrathecal gadolinium was 83% (95% CI, 51-96%). There was no significant difference in pooled diagnostic yield between MR myelography and MR myelography with intrathecal gadolinium (p = 0.512). In subgroup analysis, the pooled diagnostic yield of the epidural fluid collection was 91% (95% CI, 84-94%). In meta-regression, the diagnostic yield was unaffected regardless of consecutive enrollment, magnet strength, or 2D/3D. MR myelography had a high diagnostic yield in patients with SIH. MR myelography is non-invasive and not inferior to MR myelography with intrathecal gadolinium. • The pooled diagnostic yield of MR myelography was 86% (95% CI, 80-91%) in patients with spontaneous intracranial hypotension. • There was no significant difference in pooled diagnostic yield between MR myelography and MR myelography with intrathecal gadolinium. • MR myelography is non-invasive and not inferior to MR myelography with intrathecal gadolinium.

1.5 versus 3 Tesla structural MRI in patients with focal epilepsy.

Structural MRI is a critical component in the pre-surgical investigation of epilepsy, as identifying an epileptogenic lesion increases the chance of post-surgical seizure freedom. In general practice, 1.5T and 3T MRI scans are still the mainstream in most epilepsy centres, particularly in resource-poor countries. When 1.5T MRI is non-lesional, a repeat scan is often performed as a higher-field structural scan, usually 3T. However, it is not known whether scanning at 3T increases diagnostic yield in patients with focal epilepsy. We sought to compare lesion detection and other features of 1.5T and 3T MRI acquired in the same patients with epilepsy. MRI scans (1.5T and 3T) from 100 patients were presented in a blinded, randomized order to two neuroradiologists. The presence, location, and number of potentially epileptogenic lesions were compared. In addition, tissue contrast and the presence of motion/technical artifacts were compared using a 4-point subjective scale. Both the qualitative tissue contrast and motion/technical artifacts were improved at 3T. However, this did not result in statistically significant improvement in lesion detection. Qualitatively, five patients had subtle lesions seen only at 3T. However, minor differences in image acquisition parameters between 1.5T and 3T scans in these cases may have resulted in greater lesion visibility at 3T in four patients. Based on a general linear model analysis, the presence of a focal abnormality on EEG was predictive of the presence of a lesion at 1.5T and 3T. Repeat MRI scanning of patients with focal epilepsy at 3T using similar scan protocols does not significantly increase diagnostic yield over scanning at 1.5T; the increased signal-to-noise ratio can potentially be better allocated for novel scan sequences in order to provide more clinical value.

Long-read Amplicon Sequencing of the CYP21A2 in 48 Thai Patients With Steroid 21-Hydroxylase Deficiency

Congenital adrenal hyperplasia is most commonly caused by 21-hydroxylase deficiency (21-OHD), an autosomal recessive disorder resulting from biallelic pathogenic variants (PVs) in CYP21A2. With a highly homologous pseudogene and various types of single nucleotide and complex structural variants, identification of PVs in CYP21A2 has been challenging. To leverage long-read next-generation sequencing combined with locus-specific polymerase chain reaction (PCR) to detect PVs in CYP21A2 and to determine its diagnostic yield in patients with 21-OHD. Forty-eight Thai patients with 21-OHD comprising 38 sporadic cases and 5 pairs of siblings were enrolled. Two previously described locus-specific PCR methods were performed. Amplicons were subject to long-read sequencing. Ninety-six PVs in CYP21A2 in the 48 patients were successfully identified. The combined techniques were able to detect 26 structural chimeric variants (27%; 26/96) in 22 patients with 18 having monoallelic and 4 having biallelic chimeras. The remaining PVs were pseudogene-derived mutations (63%; 60/96), entire gene deletions (2%; 2/96), missense variants (3%; 3/96), a splice-site variant (2%; 2/96), frameshift variants (2%; 2/96), and a nonsense variant (1%; 1/96). Notably, a splice-site variant, IVS7 + 1G > T, which was identified in a pair of siblings, has not previously been reported. Our approach exploiting locus-specific PCR and long-read DNA sequencing has a 100% diagnostic yield for our cohort of 48 patients with 21-OHD.

Faecal calprotectin increases the diagnostic yield in patients with suspected small bowel disease – a multicenter retrospective cohort study

Diagnosing small bowel pathology is challenging, and the diagnostic yield of small bowel capsule endoscopy is highly variable. Faecal calprotectin is a non-invasive intestinal inflammation marker that could be used as a selection tool to identify patients who might benefit from small bowel capsule endoscopy and increase its diagnostic yield. This study aimed to investigate the value of faecal calprotectin in detecting small bowel lesions in an unselected patient population. We performed a retrospective analysis of consecutive patients who underwent small bowel capsule endoscopy at the University Hospital Basel and the University Medical Clinic Cantonal Hospital Baselland, Switzerland, between 2010 and 2018. Patients without faecal calprotectin testing were excluded from the analysis. The primary endpoint was the presence of a clinically significant small bowel finding. Patients with positive faecal calprotectin results were more likely to have small bowel findings (66.7% vs 39.4%;P= 0.007). The optimal faecal calprotectin cut-off to identify clinically significant small bowel lesions was 63 μg/g with 78.3% (95% confidence interval: 66.7-87.9) sensitivity, 47.9% (33.3-62.8) specificity, 1.50 (1.1-2.0) positive and 0.45 (0.3-0.8) negative likelihood ratios, 68.4% (61.6-74.4) positive and 60.5% (47.3-72.4) negative predictive values, and 65.0% overall accuracy. Faecal calprotectin performed best in patients with suspected inflammatory bowel disease, with 66.7% (48.2-82.0) sensitivity, 70.6% (44.0-89.7) specificity, 2.27 (1.0-4.9) positive and 0.47 (0.3-0.8) negative likelihood ratios, 81.5% (67.0-90.5) positive and 54.5% (39.7-68.6) negative predictive values, and 71.4% overall accuracy. Faecal calprotectin testing increases the diagnostic yield of small bowel capsule endoscopy and may help identify patients at risk of small bowel disease.

Diagnostic yield of image-guided biopsy in patients with suspected infectious spondylodiscitis : a prospective study from a tuberculosis-endemic country.

The aims of this study were to determine the diagnostic yield of image-guided biopsy in providing a final diagnosis in patients with suspected infectious spondylodiscitis, to report the diagnostic accuracy of various microbiological tests and histological examinations in these patients, and to report the epidemiology of infectious spondylodiscitis from a country where tuberculosis (TB) is endemic, including the incidence of drug-resistant TB. A total of 284 patients with clinically and radiologically suspected infectious spondylodiscitis were prospectively recruited into the study. Image-guided biopsy of the vertebral lesion was performed and specimens were sent for various microbiological tests and histological examinations. The final diagnosis was determined using a composite reference standard based on clinical, radiological, serological, microbiological, and histological findings. The overall diagnostic yield of the biopsy, and that for each test, was calculated in light of the final diagnosis. The final diagnosis was tuberculous spondylodiscitis in 250 patients (88%) and pyogenic spondylodiscitis in 22 (7.8%). Six (2.1%) had a noninfectious condition-mimicking infectious spondylodiscitis, and six (2.1%) had no definite diagnosis and improved without specific treatment. The diagnosis was made by image-guided biopsy in 152 patients (56%) with infectious spondylodiscitis. Biopsy was contributory in identifying 132/250 patients (53%) with tuberculous spondylodiscitis, and 20/22 patients (91%) with pyogenic spondylodiscitis. Histological examination was the most sensitive diagnostic modality, followed by Xpert MTB/RIF assay. Image-guided biopsy has a reasonably high diagnostic yield in patients with suspected infectious spondylodiscitis. A combination of histological examination, Xpert MTB/RIF assay, bacterial culture, and sensitivity provides high diagnostic accuracy in a country in which TB is endemic. Cite this article: Bone Joint J2022;104-B(1):120-126.

Angiographic diagnosis for accurate assessment of congenital porto-systemic shunt and extrahepatic portal vein obstruction in children.

Congenital porto-systemic shunt (CPSS) is a rare disease and can cause fatal complications. Accurate angiographic assessment is mandatory for proper treatment. Although technically difficult, we developed assessment techniques and assessed their accuracy. One technique came from evaluating patients with extrahepatic portal vein obstruction (EHPVO). We conducted a single center retrospective study to evaluate the efficacy of angiographic diagnostic procedure for the assessment of CPSS and EHPVO, and its impact on patients' subsequent interventions and clinical course. Eight patients with CPSS and two patients with EHPVO who underwent diagnostic angiography were included. Assessment of the intrahepatic portal vein was performed in all patients. The route of the shunt, and portal vein pressure under shunt occlusion, were also evaluated for patients with CPSS. Evaluation was first attempted with a balloon angiographic catheter (standard method). Three additional techniques were performed as needed: (i) direct wedge-catheter injection without balloon inflation, (ii) use of occlusion balloon in two patients, and (iii) hybrid angiography with sheath placement directly into the superior mesenteric vein. The standard method was sufficient in four patients. On the other hand, all three techniques were required in two patients each. One lost contact during follow up, but all other patients underwent optimal intervention. There were no complications related to the angiographic procedure. Use of direct wedge-catheter injection without balloon inflation, occlusion balloon, and hybrid catheterization improved the diagnostic yield in patients with CPSS or EHPVO.

Coronary computed tomographic angiography as gatekeeper for new-onset stable angina.

Patients with new-onset stable angina constitute a substantial part of the population seen by cardiologists. Currently, the diagnostic workup of these patients depends on the pre-test probability of having obstructive coronary artery disease. It consists of either functional testing for myocardial ischaemia or anatomical testing by using coronary computed tomographic angiography (CCTA) or invasive coronary angiography. In case the pre-test probability is > 5%, the current guidelines for the management of chronic coronary syndromes do not state a clear preference for one of the noninvasive techniques. However, based on the recently published cost-effectiveness analysis of the PROMISE trial and considering the diagnostic yield in patients with angina and nonobstructive coronary artery disease, we argue a more prominent role for CCTA as a gatekeeper for patients with new-onset stable angina.

Technological Improvements in the Genetic Diagnosis of Rett Syndrome Spectrum Disorders.

Rett syndrome (RTT) is a severe neurodevelopmental disorder that constitutes the second most common cause of intellectual disability in females worldwide. In the past few years, the advancements in genetic diagnosis brought by next generation sequencing (NGS), have made it possible to identify more than 90 causative genes for RTT and significantly overlapping phenotypes (RTT spectrum disorders). Therefore, the clinical entity known as RTT is evolving towards a spectrum of overlapping phenotypes with great genetic heterogeneity. Hence, simultaneous multiple gene testing and thorough phenotypic characterization are mandatory to achieve a fast and accurate genetic diagnosis. In this review, we revise the evolution of the diagnostic process of RTT spectrum disorders in the past decades, and we discuss the effectiveness of state-of-the-art genetic testing options, such as clinical exome sequencing and whole exome sequencing. Moreover, we introduce recent technological advancements that will very soon contribute to the increase in diagnostic yield in patients with RTT spectrum disorders. Techniques such as whole genome sequencing, integration of data from several “omics”, and mosaicism assessment will provide the tools for the detection and interpretation of genomic variants that will not only increase the diagnostic yield but also widen knowledge about the pathophysiology of these disorders.

Artificial intelligence for automatic diagnosis of biliary stricture malignancy status in single-operator cholangioscopy: a pilot study

The diagnosis and characterization of biliary strictures (BSs) is challenging. The introduction of digital single-operator cholangioscopy (DSOC) that allows direct visual inspection of the lesion and targeted biopsy sampling significantly improved the diagnostic yield in patients with indeterminate BSs. However, the diagnostic efficiency of DSOC remains suboptimal. Convolutional neural networks (CNNs) have shown great potential for the interpretation of medical images. We aimed to develop a CNN-based system for automatic detection of malignant BSs in DSOC images. We developed, trained, and validated a CNN-based on DSOC images. Each frame was labeled as a normal/benign finding or as a malignant lesion if histopathologic evidence of biliary malignancy was available. The entire dataset was split for 5-fold cross-validation. In addition, the image dataset was split for constitution of training and validation datasets. The performance of the CNN was measured by calculating the area under the receiving operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. A total of 11,855 images from 85 patients were included (9695 malignant strictures and 2160 benign findings). The model had an overall accuracy of 94.9%, sensitivity of 94.7%, specificity of 92.1%, and AUC of .988 in cross-validation analysis. The image processing speed of the CNN was 7 ms per frame. The developed deep learning algorithm accurately detected and differentiated malignant strictures from benign biliary conditions. The introduction of artificial intelligence algorithms to DSOC systems may significantly increase its diagnostic yield for malignant strictures.

Cone Beam CT Guidance Improves Transbronchial Lung Cryobiopsy Safety.

Determining the cause of diffuse parenchymal lung disease (DPLD) is challenging. While surgical lung biopsy has been the standard approach, transbronchial lung cryobiopsy (TBLC) represents a minimally invasive alternative with an acceptable safety profile and reasonable accuracy. In this study, we prospectively assessed whether the use of cone beam CT (CBCT) coupled with a novel bronchoscope holder and prophylactic administration of vasoconstricting medications decreases potential complications and improves diagnostic accuracy when performing TBLC. 33 patients presenting for evaluation of newly diagnosed DPLD were enrolled. Demographic data, pulmonary function values, chest imaging pattern, procedural information, and diagnosis were recorded. Mean patient age was 67, with the majority Caucasian (n = 26, 79%) and male (n = 20, 61%). Mean pulmonary function values revealed restrictive lung disease (76 ± 14% predicted) and diffusing capacity impairment (52 ± 16%). A non-usual interstitial pneumonia imaging pattern was commonly seen (n = 20, 61%). CBCT guided TBLC was performed in one lobe (n = 29, 88%) or two lobes (n = 4, 12%) with mean probe-to-pleura distance of 4.2 ± 1.3mm. No peri or post procedural complications occurred. 32 patients (97%) received a histological diagnosis with a final multidisciplinary conference diagnosis possible for 32 (97%). CBCT guided TBLC coupled with a novel articulating scope holder and prophylactic phenylephrine administration has the potential to increase safety and diagnostic yield for patients with newly identified DPLD. Future studies comparing different aspects of this approach in isolation and with other modalities have the potential to refine this procedure to improve patient care.

Opportunistic Screening of Patients for Hepatic Steatosis: Clinical Follow-Up and Diagnostic Yield.

Hepatic steatosis is a common incidental finding on abdominal imaging that is not always reported or recognized as having clinical significance. Because of its association with liver disease, cirrhosis, and diabetes, the aim of this study was to bring attention to this finding and provide clinical guidance to referring clinicians by inserting standardized text into radiology reports of patients with incidentally detected hepatic steatosis. Patients with incidentally discovered hepatic steatosis on abdominal ultrasound or CT had standard text inserted into the impression sections of their diagnostic imaging reports. A total of 1,256 patients whose reports were tagged between April 2016 and September 2017 were retrospectively identified and their electronic medical records reviewed to determine subsequent acknowledgment in the medical record or clinical action in response to the tagged report. Information regarding patient demographics, the type of provider who ordered the examination, and the acuity of the examination results was also recorded. Acknowledgment and subsequent clinical action were more likely in patients whose examinations was ordered by primary care providers, whose examination results were not urgent, and who were in the ultrasound group. The overall diagnostic yield in patients who underwent clinical evaluation was nonalcoholic fatty liver disease in 70%, nonalcoholic steatohepatitis in 6%, and alcoholic hepatitis in 17%. Opportunistic screening for incidental hepatic steatosis on abdominal CT and ultrasound is feasible, with substantial yield for patients with clinically important entities including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.