High Diagnostic Yield Research Articles

Integrating molecular and radiological screening tools during community-based active case-finding for tuberculosis and COVID-19 in southern Africa

ObjectivesTo evaluate diagnostic yield and feasibility of integrating testing for TB and COVID-19 using molecular and radiological screening tools during community-based active case-finding (ACF). MethodsCommunity-based participants with presumed TB and/or COVID-19 were recruited using a mobile clinic. Participants underwent simultaneous point-of-care (POC) testing for TB (sputum; Xpert-Ultra) and COVID-19 (nasopharyngeal swabs; Xpert-SARS-CoV-2). Sputum culture and SARS-CoV-2 RT-PCR served as reference standards. Participants underwent ultra-portable POC chest-radiography with computer-aided detection (CAD). TB infectiousness was evaluated using smear microscopy, cough aerosol sampling studies (CASS), and chest radiographic cavity detection. Feasibility of POC testing was evaluated via user-appraisals. Results601 participants were enrolled, with 144/601 (24.0%) reporting symptoms suggestive of TB and/or COVID-19. 16/144 (11.1%) participants tested positive for TB, while 10/144 (6.9%) tested positive for COVID-19 (2/144 [1.4%] had concurrent TB/COVID-19). 7/16 (43.8%) individuals with TB were probably infectious. Test-specific sensitivity and specificity (95% CI) were: Xpert-Ultra 75.0% (42.8-94.5) and 96.9% (92.4-99.2); Xpert-SARS-CoV-2 66.7% (22.3-95.7) and 97.1% (92.7-99.2). Area-under-the-curve (AUC) for CAD4TB was 0.90 (0.82-0.97). User appraisals indicated POC Xpert to have ‘good’ user-friendliness. ConclusionsIntegrating TB/COVID-19 screening during community-based ACF using POC molecular and radiological tools is feasible, has a high diagnostic yield, and can identity probably infectious persons.

Diagnostic Accuracy of Ultrasound Guided Percutaneous Pleural Needle Biopsy for Malignant Pleural Mesothelioma

Background/Objectives: Ultrasound (US) has been progressively spreading as the most useful technique for guiding biopsies and fine-needle aspirations that are performed percutaneously. Malignant pleural mesothelioma (MPM) represents the most common malignant pleural tumour. Thoracoscopy represents the gold standard for diagnosis, although conditions hampering such diagnostic approach often coexist. The Objective was to determine whether ultrasound-guided percutaneous needle biopsy (US-PPNB) has a high diagnostic accuracy and represents a safe option for diagnosis of MPM. Methods: US-PPNB of pleural lesions suspected for MPM in patients admitted from January 2021 to June 2023 have been retrospectively analyzed. An 18-gauge semi-automatic spring-loaded biopsy system (Medax Velox 2®) was used by experienced pneumologists. The obtained specimens were histologically evaluated and defined as adequate or non-adequate for diagnosis according to whether the material was considered appropriate or not for immunohistochemistry (IHC) analysis. The primary objective of the study was the diagnostic yield for a tissue diagnosis. Results: US-PPNB was diagnostic of MPM in 15 out of 18 patients (sensitivity: 83.39%; specificity: 100%; PPV: 100%). Three patients with non-adequate US-PPNB underwent thoracoscopy for diagnosis. We found significant differences in terms of mean pleural lesion thickness between patients with adequate and not-adequate biopsy (15.4 mm (SD: 9.19 mm) and 3.77 mm (SD: 0.60 mm), p < 0.0010. In addition, a significant positive correlation has been observed between diagnostic accuracy and FDG-PET avidity value. Conclusions: US-PPNB performed by a pneumologist represents a valid procedure with a high diagnostic yield and accuracy for the diagnosis of MPM, and may be considered as an alternative option in patients who are not suitable for thoracoscopy.

Endoscopic Diagnosis of Small Bowel Tumor

Recent technological advances, including capsule endoscopy (CE) and balloon-assisted endoscopy (BAE), have revealed that small intestinal disease is more common than previously thought. CE has advantages, including a high diagnostic yield, discomfort-free, outpatient basis, and physiological images. BAE enabled endoscopic diagnosis and treatment in the deep small bowel. Computed tomography (CT) enterography with negative oral contrast can evaluate masses, wall thickening, and narrowing of the small intestine. In addition, enhanced CT can detect abnormalities outside the gastrointestinal tract that endoscopy cannot evaluate. Each modality has its advantages and disadvantages, and a good combination of multiple modalities leads to an accurate diagnosis. As a first-line modality, three-phase enhanced CT is preferred. If CT shows a mass, stenosis, or wall thickening, a BAE should be selected. If there are no abnormal findings on CT and no obstructive symptoms, CE should be selected. If there are significant findings in the CE, determine the indication for BAE and its insertion route based on these findings. Early diagnosis of small intestinal tumors is essential for favorable outcomes. For early diagnosis, the possibility of small bowel lesions should be considered in patients with unexplained symptoms and signs after examination of the upper and lower gastrointestinal tract.

Transbronchial Lung Cryobiopsies, Transbronchial Forceps Lung Biopsies, and Surgical Lung Biopsies in Mechanically Ventilated Patients with Acute Hypoxemic Respiratory Failure: A Retrospective Cohort Study.

Lung biopsies are sometimes performed in mechanically ventilated patients with acute hypoxemic respiratory failure (AHRF) of unknown etiology to guide patient management. While surgical lung biopsies (SLB) offer high diagnostic rates, they may also cause significant complications. Transbronchial forceps lung biopsies (TBLB) are less invasive but often produce non-contributive specimens. Transbronchial lung cryobiopsies (TBLC) yield specimens of potentially better quality than TBLB, but due to their novel implementation in the intensive care unit (ICU), their accuracy and safety are still unclear. Our main objective was to evaluate the risk of adverse events in patients with AHRF following the three biopsy techniques. Our secondary objectives were to assess the diagnostic yield and associated modifications of patient management of each technique. We conducted a retrospective cohort study comparing TBLC, TBLB, and SLB in mechanically ventilated patients with AHRF. The primary outcome was the proportion of patients with at least one complication, and secondary outcomes included complication rates, diagnostic yields, treatment modifications, and mortality. Of the 26 patients who underwent lung biopsies from 2018 to 2022, all TBLC and SLB patients and 60% of TBLB patients had at least one complication. TBLC patients had higher unadjusted numbers of total and severe complications, but also worse Sequential Organ Failure Assessment scores and P/F ratios. A total of 25 biopsies (25/26, 96%) provided histopathological diagnoses, 88% (22/25) of which contributed to patient management. ICU mortality was high for all modalities (63% for TBLC, 60% for TBLB and 50% for SLB). All biopsy methods had high diagnostic yields and the great majority contributed to patient management; however, complication rates were elevated. Further research is needed to determine which patients may benefit from lung biopsies and to determine the best biopsy modality.

The value of contrast-enhanced ultrasound in percutaneous biopsy of retroperitoneal masses.

To evaluate the diagnostic yield of contrast-enhanced ultrasound (CEUS)-guided biopsy of retroperitoneal masses (RMs). Between 2006 and 2023, 87 patients presented at our US center for biopsy of an RM. In all biopsies, CEUS was performed prior to the intervention. The technical success rate of biopsy, the presence of diagnostic tissue in solid tumor biopsy samples, the accuracy of the biopsy and the occurrence of post-interventional complications were evaluated. A US-guided biopsy could be conducted in 84/87 cases (96.6%). In 3/87 cases (3.4%), US-guided biopsy was impossible because the planned needle path was obstructed by vital structures. Of 84 lesions, 80 (95.2%) were solid lesions, and 4 (4.8%) were lesions containing fluid. In all solid tumors, 80/80 (100%), diagnostic vital tissue was successfully obtained. CEUS-guided biopsy showed a sensitivity of 93.2%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 72.2%, and a diagnostic accuracy of 94.2% for the differentiation between malignant and benign RMs. In one of the 84 cases (1.2%), there was a complication of postinterventional abdominal pain. Percutaneous CEUS-guided biopsy is a safe procedure with a high diagnostic yield and a low complication rate.

Yield of capsule endoscopy and subsequent device-assisted enteroscopy: Experience at an Australian tertiary centre.

Small bowel capsule endoscopy (SBCE) and device-assisted enteroscopy (DAE) have an established role in the investigation and management of small bowel pathology. Previous studies have reported on the yield of SBCE (60%) and DAE (57%), but none have been in an Australian setting. To determine the yield of SBCE and any DAE performed as a direct consequence of SBCE in an Australian referral centre. A single-centre retrospective study was conducted at a tertiary hospital in Australia, enrolling consecutive patients between 1 January 2009 and 31 December 2021 undergoing SBCE. Data were collected with respect to demographics, procedural factors and findings, as well as findings and interventions of any DAE procedures performed after the SBCE. 1214 SBCEs were performed, with a median age of 66 years old (60.8% men). The predominant indications were anaemia (n = 853, 70.2%) and overt gastrointestinal bleeding (n = 320, 26.4%). Of the complete small bowel studies (1132/1214, 93.2%), abnormal findings were detected in 588 cases (51.9%), most commonly angioectasias (266/588, 45.2%), erosions (106/588, 18.0%) and ulcers (97/588, 8.6%). 165 patients underwent a DAE (117 antegrade, 48 retrograde). Antegrade DAE had a higher yield than retrograde DAE (77.8% vs 54.2%; P = 0.002) and a higher rate of intervention (69.2% vs 37.5%; P < 0.001). In this largest single-centre cohort of patients undergoing SBCE to date, there is a similar yield of abnormal findings compared to existing literature. DAE, especially with an antegrade approach, had high diagnostic and therapeutic yield when pursued after a positive SBCE study.

Protocolo diagnóstico de la colestasis

The concept of cholestasis refers to difficulty or stoppage of bile flow. It is a common clinical problem that can be the manifestation of multiple diseases. A distinction can be drawn between intrahepatic cholestasis, when there is abnormality in the liver parenchyma, and extrahepatic cholestasis, if the obstruction is located in the common bile duct. A detailed case history and physical examination are essential in order to guide the diagnosis. An abdominal ultrasound is the first imaging test to be performed. In the presence of a normal or inconclusive ultrasound, the study should be expanded with other more specific imaging tests. If malignancy is suspected, an abdominal computed tomography scan should be the first diagnostic procedure. An oral endoscopic ultrasound and magnetic resonance cholangiopancreatography are examinations with a high diagnostic yield that is comparable between them. Endoscopic retrograde cholangiopancreatography allows for direct visualization of the bile duct with the possibility of performing treatment.

Focused Exome Sequencing Gives a High Diagnostic Yield in the Indian Subcontinent

The genetically isolated yet heterogeneous and highly consanguineous Indian population has shown a higher prevalence of rare genetic disorders. However, there is a significant socioeconomic burden for genetic testing to be accessible to the general population. In the current study, we analyzed next-generation sequencing data generated through focused exome sequencing from individuals with different phenotypic manifestations referred for genetic testing to achieve a molecular diagnosis. We reported pathogenic or likely pathogenic variants in 280 out of 833 cases with a diagnostic yield of 33.6%. Homozygous sequence and copy number variants were found as positive diagnostic findings in 131 (15.7%) cases owing to the high consanguinity in the Indian population. No relevant findings related to reported phenotype were identified in 6.2% of the cases. Patients referred for testing due to metabolic disorder and neuromuscular disorder had higher diagnostic yields. Carrier testing of asymptomatic individuals with a family history of the disease, through focused exome sequencing, achieved positive diagnosis in 54 of 118 cases tested. We also reported copy number variants in trans with single nucleotide variants and mitochondrial variants in a few of the cases. The diagnostic yield and the findings from this study signify that a focused exome test is a good lower-cost alternative for whole exome and whole genome sequencing and as a first-tier approach to genetic testing.

High Tidal Volume, High Positive End Expiratory Pressure and Apneic Breath Hold Strategies (Lung Navigation Ventilation Protocol) With Cone Beam Computed Tomography Bronchoscopic Biopsy of Peripheral Lung Lesions: Results in 100 Patients.

A dedicated anesthesia protocol for bronchoscopic lung biopsy-lung navigation ventilation protocol (LNVP)-specifically designed to mitigate atelectasis and reduce unnecessary respiratory motion, has been recently described. LNVP demonstrated significantly reduced dependent ground glass, sublobar/lobar atelectasis, and atelectasis obscuring target lesions compared with conventional ventilation. In this retrospective, single-center study, we examine the impact of LNVP on 100 consecutive patients during peripheral lung lesion biopsy. We report the incidence of atelectasis using cone beam computed tomography imaging, observed ventilatory findings, anesthesia medications, and outcomes, including diagnostic yield, radiation exposure, and complications. Atelectasis was observed in a minority of subjects: ground glass opacity atelectasis was seen in 30 patients by reader 1 (28%) and in 18 patients by reader 2 (17%), with good agreement between readers (κ = 0.78). Sublobar/lobar atelectasis was observed in 23 patients by reader 1 and 26 patients by reader 2, also demonstrating good agreement (κ = 0.67). Atelectasis obscured target lesions in very few cases: 0 patients (0%, reader 1) and 3 patients (3%, reader 2). Diagnostic yield was 85.9% based on the AQuIRE definition. Pathology demonstrated 57 of 106 lesions (54%) were malignant, 34 lesions (32%) were benign, and 15 lesions (14%) were nondiagnostic. Cone beam computed tomography images confirmed low rates of atelectasis, high tool-in-lesion confirmation rate, and high diagnostic yield. LNVP has a similar safety profile to conventional bronchoscopy. Most patients will require intravenous fluid and vasopressor support. Further study of LNVP and other ventilation protocols are necessary to understand the impact of ventilation protocols on bronchoscopic peripheral lung biopsy.

Role of Novel Motorized Enteroscopy in the Evaluation of Small Bowel Diseases: A Systematic Review and Meta-analysis.

Motorized spiral enteroscopy (MSE) has recently been introduced for small bowel evaluation. In this systematic review and meta-analysis, we aim to evaluate the safety and efficacy of MSE for evaluation of small bowel diseases. A literature search was performed in Embase, PubMed, Medline databases for studies evaluating MSE between January -2010 and October-2022. The primary outcome of the study was diagnostic yield with MSE. Secondary outcomes included technical success, procedure duration, depth of maximum insertion (DMI), rate of pan-enteroscopy and adverse events. 10 studies with 961 patients [581 (60.5%) males] were included in the analysis. 1068 MSE procedures were performed by antegrade route in 698, retrograde route in 215 and bidirectional in 155 patients. Technical success was achieved in 94.9% (95% CI 92.9% to 96.4%) procedures. The pooled diagnostic yield of MSE was 73.7% (95% CI 70.7% to 76.4%). Pooled rate of pan-enteroscopy by antegrade route was 21.9% (95% CI 18.1% to 26.1%), retrograde route was 6.9% (95% CI 2.4% to 18.3%) and combined route was 61.2% (95% CI 52.4% to 69.3%). Pooled rate of major adverse events was 1.9% (95% CI 1.2% to 3.2%). MSE is a safe and effective tool for evaluating small bowel disorders. High diagnostic yield and low rate of adverse events make it a potential alternative to balloon enteroscopy. However, comparative trials are required in the future.

Clinical Utility and Diagnostic Yield of Genetic Testing for Inherited Neuromuscular Disorders in a Single, Large Neuromuscular Center.

Most published studies on the clinical utility of genetic testing for neuromuscular diseases (NMDs) focus on disease-specific cohorts and/or involve multiple centers. The aim of this study was to examine the clinical utility and diagnostic yield of genetic testing at a single, large neuromuscular center. Unlike previous studies, this study is unique in that it includes a broad array of patients at a single, large neuromuscular center, providing real-world data that may assist both neuromuscular specialists as well as general neurologists in decision-making regarding the need for genetic testing in patients with suspected NMDs. Genetic testing results were reviewed for all patients who underwent testing through a single genetic testing company for NMDs in this single laboratory at a large neuromuscular center from 2015 to 2020. Retrospective chart reviews were performed to determine whether genetic testing results conferred a specific NMD diagnosis, including cases where a variant of uncertain significance (VUS) was identified. Genetic testing was pursued for 192 patients. A positive result, defined as a pathogenic mutation, a VUS, or both, was found in 77.1%. A definitive diagnosis was conferred in 35.9%. The most common testing indication was suspected neuropathy (53.3%), and the indication with the highest diagnostic yield was suspected myopathy (48.7%). This study provides further evidence of the clinical utility of genetic testing for NMDs in a real-world setting with over one-third of patients tested receiving a definitive diagnosis. Over time, genetic testing will continue to become increasingly accessible, cost-effective, and sensitive, which will lead to even more utilization.

Cone-beam CT-based Navigation With Augmented Fluoroscopy of the Airways for Image-guided Bronchoscopic Biopsy of Peripheral Pulmonary Nodules: A Prospective Clinical Study.

Cone-beam computed tomography (CBCT) and augmented fluoroscopy (AF), in which intraprocedural CBCT data is fused with fluoroscopy, have been utilized as a novel image-guidance technique for biopsy of peripheral pulmonary lesions. The aim of this clinical study is to determine the safety and diagnostic performance of CBCT-guided bronchoscopy with advanced software tools for procedural planning and navigational guidance with AF of the airways for biopsy of peripheral pulmonary nodules. Fifty-two consecutive subjects were prospectively enrolled in the AIRWAZE study (December 2018 to October 2019). Image-guided bronchoscopic biopsy procedures were performed under general anesthesia with specific ventilation protocols in a hybrid operating room equipped with a ceiling-mounted C-arm system. Procedural planning and image-guided bronchoscopy with CBCT and AF were performed using the Airwaze investigational device. A total of 58 pulmonary lesions with a median size of 19.0mm (range 7 to 48mm) were biopsied. The overall diagnostic yield at index procedure was 87.9% (95% CI: 77.1%-94.0%). No severe adverse events related to CBCT-guided bronchoscopy, such as pneumothorax, bleeding, or respiratory failure, were observed. CBCT-guided bronchoscopic biopsy with augmented fluoroscopic views of the airways and target lesion for navigational guidance is technically feasible and safe. Three-dimensional image-guided navigation biopsy is associated with high navigational success and a high diagnostic yield for peripheral pulmonary nodules.

Pentraxin 3 in Myocarditis: Proof-of-Principle Assessment as a Diagnostic and Prognostic Biomarker.

Pentraxin 3 (PTX3) is an acute phase protein produced in various tissues in response to microbial and sterile stimuli, which regulates the inflammation outcomes. PTX3 has not been investigated in myocarditis. Our aim was to assess circulating and cardiac tissue expression of PTX3 in 55 patients with myocarditis proven by magnetic resonance and/or endomyocardial biopsy. A major proportion of patients with myocarditis displayed significantly increased plasma PTX3 levels as compared with controls (26/30 vs. 0/10), with higher diagnostic yield than conventional biomarkers in the study group. Cardiac tissue analysis revealed PTX3 expression in all patients (40/40), with viral myocarditis exhibiting higher signal intensity than autoimmune myocarditis, andwith a predominant localization in cardiomyocytes. Abnormal plasma PTX3 was associated with systolic dysfunction and heart failure at presentation. Interestingly, patients who recovered by 12months had higher baseline PTX3 levels. Our preliminary data support the potential use of PTX3 as a biomarker in myocarditis.

Diagnostic findings and yield of investigations for children with developmental regression.

Childhood conditions that feature developmental regression are poorly understood. Phenotype-genotype characterization and diagnostic yield data are needed to inform clinical decision-making. The aim of this study was to report the conditions featuring developmental regression and assess diagnostic yields of investigations. A retrospective chart review of children presenting with developmental regression to a tertiary pediatric genetic clinic between 2018 and 2021 was performed. Of 99 children, 30% (n = 30) had intellectual disability (ID), 21% (n = 21) were autistic, 39% (n = 39) were autistic with ID, and 9% (n = 9) did not have ID or autism. Thirty-two percent (n = 32) of children received a new diagnosis, including eight molecular findings not previously reported to feature developmental regression. Of the children investigated, exome sequencing (ES) provided the highest diagnostic yield (51.1%, n = 24/47), highest (63.6%, n = 14/22) for children with ID, 50% for autistic children with ID (n = 6/12) and children without autism or ID (n = 3/6), and 14.3% (n = 1/7) for autistic children without ID. We highlight the conditions that feature developmental regression and report on novel phenotypic expansions. The high diagnostic yield of ES, regardless of autism or ID diagnosis, indicates the presence of developmental regression as an opportunity to identify the cause, including for genetic differences not previously reported to include regression.

Stereotactic frame-based biopsy of infratentorial lesions via the suboccipital-transcerebellar approach with the Zamorano-Duchovny stereotactic system—a retrospective analysis of 79 consecutive cases

ObjectiveLesions of the posterior fossa (brainstem and cerebellum) are challenging in diagnosis and treatment due to the fact that they are often located eloquently and total resection is rarely possible. Therefore, frame-based stereotactic biopsies are commonly used to asservate tissue for neuropathological diagnosis and further treatment determination. The aim of our study was to assess the safety and diagnostic success rate of frame-based stereotactic biopsies for lesions in the posterior fossa via the suboccipital-transcerebellar approach.MethodsWe performed a retrospective database analysis of all frame-based stereotactic biopsy cases at our institution since 2007. The aim was to identify all surgical cases for infratentorial lesion biopsies via the suboccipital-transcerebellar approach. We collected clinical data regarding outcomes, complications, diagnostic success, radiological appearances, and stereotactic trajectories.ResultsA total of n = 79 cases of stereotactic biopsies for posterior fossa lesions via the suboccipital-transcerebellar approach (41 female and 38 male) utilizing the Zamorano-Duchovny stereotactic system were identified. The mean age at the time of surgery was 42.5 years (± 23.3; range, 1–87 years). All patients were operated with intraoperative stereotactic imaging (n = 62 MRI, n = 17 CT). The absolute diagnostic success rate was 87.3%. The most common diagnoses were glioma, lymphoma, and inflammatory disease. The overall complication rate was 8.7% (seven cases). All patients with complications showed new neurological deficits; of those, three were permanent. Hemorrhage was detected in five of the cases having complications. The 30-day mortality rate was 7.6%, and 1-year survival rate was 70%.ConclusionsOur data suggests that frame-based stereotactic biopsies with the Zamorano-Duchovny stereotactic system via the suboccipital-transcerebellar approach are safe and reliable for infratentorial lesions bearing a high diagnostic yield and an acceptable complication rate. Further research should focus on the planning of safe trajectories and a careful case selection with the goal of minimizing complications and maximizing diagnostic success.

Capsule endoscopy for obscure gastrointestinal bleed in the tropics: A single-center experience on 350 patients.

Obscure gastrointestinal bleed (OGIB), now called small bowel bleed (SBB), comprises 5% to10% of all gastrointestinal (GI) bleed episodes and capsule endoscopy (CE) is a tool for its evaluation. Studies on CE in a large sample of SBB patients from the tropics are limited. We did a retrospective analysis of a prospectively maintained database of patients with SBB undergoing CE using PillCam or MiroCam CE. Of 350 patients (age 52.4 ± 17.4years; 248 [70.9%] male) undergoing CE, 243 (69.4%) and 107 (30.6%) had overt and occult SBB, respectively. CE detected lesions in 244 (69.7%) patients (single lesion in 172 [49.1%]; multiple in 72 [20.6%]). The single lesions included vascular malformations (52, 14.9%), ulcer/erosion (47, 13.4%), tumor (24, 6.9%), hookworm (19, 5.4%), stricture (15, 4.3%), hemobilia (1, 0.3%) and blood without identifiable lesion (9, 2.6%). Of 72 with multiple lesions, ulcer with stricture was the commonest finding (n = 43, 12.3%). No abnormality was detected in 106 (30.3%) patients. The frequency of lesion detection was comparable among patients with overt and occult SBB (173/243, 71.2% vs. 71/107, 66.3%, respectively; p = 0.4). Younger patients (0 to 39years) more often had multiple lesions on CE than the older (≥ 40years) ones (26/76, 34.2% vs. 46/228, 20.2%, respectively; p = 0.001). CE has a high diagnostic yield in SBB in the tropics, regardless of the type of bleed or of CE brand and the duration of recording. Multiple lesions associated with SBB are commoner among younger (< 40years) patients.

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

[18F]FET PET/MRI: An Accurate Technique for Detection of Small Functional Pituitary Tumors.

Small functional pituitary tumors can cause severely disabling symptoms and early death. The gold standard diagnostic approach includes laboratory tests and MRI, with or without inferior petrosal sinus sampling (IPSS). In up to 40% of patients, however, the source of excess hormone production remains unidentified or uncertain. This excludes patients from surgical, Gamma Knife, and CyberKnife therapy and adversely affects overall cure rates. We here assess the diagnostic yield of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) PET/MRI for detection of small functional pituitary tumors in these patients. Methods: This retrospective analysis included patients with Cushing disease (CD) but prior negative or inconclusive MRI results who underwent [18F]FET PET/MRI between February 1, 2021, and December 1, 2022. PET/MR images and MR images alone were evaluated by experienced nuclear radiologists, neuroradiologists, or radiologists. Postoperative tissue analysis (when performed) was used as a reference standard to assess diagnostic metrics (i.e., sensitivity and positive predictive value). Results were also compared with previously obtained MR images, preceding IPSS, and clinical or biochemical follow-up. Results: Twenty-two patients (68% female; mean age ± SD, 48 ± 15 y; range, 24-68 y) were scanned. All patients showed a clear metabolic focus on [18F]FET PET, whereas reading of the MRI alone yielded a suspected lesion in only 50%. Fifteen patients underwent surgery directed at the [18F]FET-positive focus. Tissue analysis confirmed a pituitary adenoma/pituitary neuroendocrine tumor of the corticotroph cell type (TPIT lineage) in 10 of 15 and a pituicytoma in 1 of 15, rendering a sensitivity of 100% and a positive predictive value of 73%. Lateralization was more accurate with [18F]FET PET/MRI than with IPSS in 33%. Twelve of 16 (75%) patients who received surgical, Gamma Knife, or CyberKnife therapy after [18F]FET PET/MRI reached short-term remission. Conclusion: [18F]FET PET/MRI shows a high diagnostic yield for localizing small functional pituitary tumors. This multimodal imaging technique provides a welcome improvement for diagnosis, planning of surgery, and clinical outcome in patients with Cushing disease, particularly those with repeated negative or inconclusive MRI results with or without IPSS.

Virtual bronchoscopic navigation with intraoperative cone-beam CT for the diagnosis of peripheral pulmonary nodules

ObjectiveTransbronchial biopsy is a safe manner with fewer complications than percutaneous transthoracic needle biopsy; however, the current diagnostic yield is still necessitating further improvement. We aimed to evaluate the diagnostic yield of using virtual bronchoscopic navigation (VBN) and cone-beam CT (CBCT) for transbronchial biopsy and to investigate the factors that affected the diagnostic sensitivity.MethodsWe retrospectively investigated 255 patients who underwent VBN-CBCT-guided transbronchial biopsy at our two centers from May 2021 to April 2022. A total of 228 patients with final diagnoses were studied. Patient characteristics including lesion size, lesion location, presence of bronchus sign, lesion type and imaging tool used were collected and analyzed. Diagnostic yield was reported overall and in groups using different imaging tools.ResultsThe median size of lesion was 21 mm (range of 15.5–29 mm) with 46.1% less than 2 cm in diameter. Bronchus sign was present in 87.7% of the patients. The overall diagnostic yield was 82.1%, and sensitivity for malignancy was 66.3%. Patients with lesion > 2 cm or with bronchus sign were shown to have a significantly higher diagnostic yield. Four patients had bleeding and no pneumothorax occurred.ConclusionGuided bronchoscopy with VBN and CBCT was an effective diagnostic method and was associated with a high diagnostic yield in a safe manner. In addition, the multivariant analysis suggested that lesion size and presence of bronchus sign could be a predictive factor for successful bronchoscopic diagnosis.

Impact of deep phenotyping: high diagnostic yield in a diverse pediatric population of 172 patients through clinical whole-genome sequencing at a single center.

Background: Pediatric patients with undiagnosed conditions, particularly those suspected of having Mendelian genetic disorders, pose a significant challenge in healthcare. This study investigates the diagnostic yield of whole-genome sequencing (WGS) in a pediatric cohort with diverse phenotypes, particularly focusing on the role of clinical expertise in interpreting WGS results. Methods: A retrospective cohort study was conducted at Acibadem University's Maslak Hospital in Istanbul, Turkey, involving pediatric patients (0-18years) who underwent diagnostic WGS testing. Clinical assessments, family histories, and previous laboratory and imaging studies were analyzed. Variants were classified and interpreted in conjunction with clinical findings. Results: The cohort comprised 172 pediatric patients, aged 0-5years (62.8%). International patients (28.5%) were from 20 different countries. WGS was used as a first-tier approach in 61.6% of patients. The diagnostic yield of WGS reached 61.0%, enhanced by reclassification of variants of uncertain significance (VUS) through reverse phenotyping by an experienced clinical geneticist. Consanguinity was 18.6% of the overall cohort. Dual diagnoses were carried out for 8.5% of solved patients. Discussion: Our study particularly advocates for the selection of WGS as a first-tier testing approach in infants and children with rare diseases, who were under 5years of age, thereby potentially shortening the duration of the diagnostic odyssey. The results also emphasize the critical role of a single clinical geneticist's expertise in deep phenotyping and reverse phenotyping, which contributed significantly to the high diagnostic yield.