Nondiagnostic Results Research Articles

CT-guided percutaneous transthoracic needle biopsy for anterior mediastinal lymphoma: the role of PET/CT.

Computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) is not recommended as the diagnostic modality of choice for anterior mediastinal lymphoma, despite its advantages of minimal invasiveness and easy accessibility. To identify the modifiable risk factors for non-diagnostic results from CT-guided PTNB for anterior mediastinal lymphoma. This retrospective study identified CT-guided PTNB for anterior mediastinal lesions diagnosed as lymphoma between May 2007 and December 2021. The diagnostic sensitivity and complications were investigated. The appropriateness of PTNB targeting was evaluated using positron emission tomography (PET)/CT and images from intra-procedural CT-guided PTNB. Targeting was considered inappropriate when the supposed trajectory of the cutting needle was within a region of abnormally low metabolism. The risk factors for non-diagnostic results were determined using logistic regression analysis. A total of 67 PTNBs in 60 patients were included. The diagnostic sensitivity for lymphoma was 76.1% (51/67), with an immediate complication rate of 4.5% (3/67). According to the PET/CT images, PTNB targeting was inappropriate in 10/14 (71.4%) of the non-diagnostic PTNBs but appropriate in all diagnostic PTNBs (P <0.001). Inappropriate targeting was the only significant risk factor for non-diagnostic results (odds ratio = 203.69; 95% confidence interval = 8.17-999.99; P = 0.001). The number of specimen acquisitions was not associated with non-diagnostic results (P = 0.40). Only inappropriate targeting of the non-viable portion according to PET/CT was an independent risk factor for non-diagnostic results. Acquiring PET/CT scans before biopsy and targeting the viable portion on PET/CT may help improve the diagnostic sensitivity of PTNB.

Usefulness of contrast-enhanced ultrasound-guided biopsy for suspected viable hepatocellular carcinoma after treatment: a single-arm prospective study.

The utility of contrast-enhanced ultrasound (CEUS)-guided liver biopsy in patients with treated hepatocellular carcinoma (HCC) was evaluated. This study prospectively enrolled 36 patients (mean age±standard deviation [SD], 65.3±9.2 years; 31 men) who underwent CEUS-guided biopsy for treated HCC between September 2020 and April 2022, constituting the CEUS group. An additional 60 patients (mean age±SD, 60.7±12.3 years; 50 men) who underwent B-mode image-guided biopsy for treated HCC between January 2017 and December 2018 were retrospectively enrolled in the B-mode, or control, group. Biopsy success rates were compared between CEUS and B-mode groups using the chi-square test. The biopsy success rate in the CEUS group was 88.9% (32 of 36 patients), which was significantly higher than the 70.0% (42 of 60 patients) observed in the B-mode group (P=0.044). No significant difference was found between CEUS and B-mode groups in the size of the lesions targeted for biopsy (mean±SD, 3.8±2.3 cm vs. 3.7±3.3 cm, respectively; P=0.332). For both the whole tumor and the viable tumor, conspicuity scores were significantly higher on CEUS than on grayscale ultrasound in the CEUS group (whole tumor: 2.7±0.5 vs. 1.8±0.9, P<0.001; viable tumor: 2.6±0.7 vs. 1.4±0.8, P<0.001). Relative to non-diagnostic results, diagnostic results more frequently exhibited a late mild washout pattern (87.5% [28 of 32] vs. 25.0% [1 of 4], P=0.004). No significant difference in the arterial enhancement pattern was noted between these subgroups (P=0.415). By increasing the viable-tumor conspicuity, CEUS-guided biopsy is useful for confirmative histopathologic diagnosis in patients with treated HCC.

THE IMPACT OF PATIENT ANXIETY AND PAIN PERCEPTION ON THE ADEQUACY OF THYROID FINE-NEEDLE ASPIRATION BIOPSY SAMPLES: A PROSPECTIVE STUDY.

Fine-needle aspiration biopsy (FNAB) is the most accurate diagnostic method to assess the malignancy risk of thyroid nodules. However, non-diagnostic results may delay diagnosis, cause unnecessary interventions, and distress patients. We aimed to determine whether a correlation exists between patients' situational anxiety, pain perception and non-diagnostic cytology results. The prospective study included patients who underwent thyroid FNAB at the Endocrinology Clinic of Sultan Abdulhamid Training and Research Hospital between 11/2022 and 02/2023. The State-Trait Anxiety Inventory (STAI) questionnaire and visual analogue scale (VAS) assessed situational anxiety and pain in patients undergoing biopsy procedures. We evaluated whether the STAI-S and VAS score is related to non-diagnostic results. Of the 119 patients included in the study, 98 were female, and 21 were male. 25 (21%) nodules were non-diagnostic. The patients' mean STAI-S score before the biopsy was 47.31±12.37, and the mean VAS score after the thyroid biopsy was 2.57±1.51. A statistically significant relation was found between the patient's STAI-S score and VAS score and the cytology result of non-diagnostic (p= 0.001 and p=0.008). In univariate logistic regression, high pre-procedural anxiety (OR:3.09, 95% CI:1.07-8.94, P =0.037) and VAS score (OR:1.57, 95% CI: 1.17-2.10, P =0.002) were associated with non-diagnostic cytology. In multivariate logistic regression analysis, VAS score (OR: 1.59, 95% CI: 1.07-2.34, p=0.019) was still an independent factor related to specimen adequacy. Anxiety level and pain perception during FNAB may be considered risk factors for non-diagnostic cytology. Thus, reducing anxiety and pain may decrease the incidence of non-diagnostic outcomes.

Core needle biopsy: an efficacious adjunct to cytological diagnosis in thyroid tumours suspected of anaplastic carcinoma - single-centre experience.

Ultrasound-guided fine- needle aspiration biopsy (FNAB) remains the primary method for diagnosing thyroid nodules, providing adequate information for definitive diagnosis and treatment decisions in most cases. However, cytological examinations sometimes yield inconclusive or non-diagnostic results. For rapidly growing tumours with suspected malignancy, a swift and accurate diagnosis is crucial to initiate timely treatment. Cases suggestive of anaplastic thyroid cancer (ATC) or poorly differentiated cancer present unique challenges in obtaining satisfactory diagnostic material through FNAB, due to advanced necrosis or extensive inflammatory components. In these instances, core needle biopsy (CNB) emerges as a complementary diagnostic tool when FNAB results are ambiguous. This study aimed to evaluate the effectiveness of CNB in diagnosing rapidly growing thyroid tumours with clinical indication of ATC. Between 2019-2023, 31 CNBs were performed on large, rapidly expanding thyroid tumours. All cases exhibited clinical signs of malignancy, with previous FNAB outcomes being either equivocal or inconclusive. The subsequent CNBs demonstrated accurate results with minimal complications among the patients. While reservations about CNB for thyroid nodules persist, it offers a valuable diagnostic alternative, potentially preventing unwarranted surgical biopsy or removal of the thyroid. Core needle biopsy deployment should be judicious, reserved for select cases, and carried out in a hospital environment to ensure diagnostic precision with the least risk of complications.

Unveiling diagnostic prowess: a comparative study of exercise treadmill test and CT coronary in coronary artery disease detection in Pakistan (2021-2023).

Coronary Artery Disease (CAD) is a global health concern, with diagnostic modalities and risk factors that exhibit regional variations. This study, conducted at the Islamabad Diagnostic Center, Pakistan, aimed to provide a comprehensive assessment of CAD prevalence, severity, and associated risk factors, while also evaluating the diagnostic accuracy of Computed Tomography Coronary Test (CTT) and Exercise Treadmill Test (ETT) in a cohort of 2909 patients. Among the patients assessed via CT Coronary scans, CAD was universally observed, presenting with varying degrees of severity. Our findings indicated that 24.5% of patients had mild CAD, 28.6% exhibited mild to moderate CAD, 16.3% were diagnosed with moderate CAD, 18.4% demonstrated moderate to severe CAD, and 20.4% displayed severe CAD. This spectrum underscores the diverse nature of CAD within the study population. In addition to CTT, we conducted a detailed evaluation of ETT results in 49 patients. These results revealed that 55.1% of patients tested positive for ischemia during the exercise test, emphasizing the prevalence of cardiac stress and underlying CAD. Conversely, 32.7% of patients exhibited negative ETT results, indicating favorable cardiac tolerance during physical activity. A subset of patients yielded non-diagnostic or inconclusive results, necessitating further clinical assessment. Disease history analysis showed a dichotomy within the cohort, with 20.4% having a known medical history and 79.6% possessing an unknown disease history, highlighting the importance of comprehensive medical records in clinical practice. Hypertension, a critical cardiovascular risk factor, was identified in 87.8% of patients, underscoring its significance. Smoking history displayed notable variation, with 69.4% categorized as smokers, 14.3% as ex-smokers, and 10.2% as non-smokers. Lipid profile analysis indicated that 69.4% of patients had abnormal lipid levels. To assess the diagnostic accuracy of CTT and ETT, we calculated Positive Predictive Values (PPV) and Negative Predictive Values (NPV). CTT exhibited a PPV of approximately 5.99% and an NPV of approximately 4.40%, whereas ETT displayed a higher PPV of around 26.44% and a substantially higher NPV of about 49.24%. This study offers valuable insights into CAD prevalence, severity, and associated risk factors in a Pakistani cohort, emphasizing the importance of holistic risk assessment and tailored interventions in clinical practice. Our findings also highlight the diagnostic utility of ETT in CAD assessment.

Conventional Cytogenetic Analysis and Array CGH+SNP Identify Essential Thrombocythemia (ET)/Prefibrotic Primary Myelofibrosis (pre-PMF) Patients Who Are at Risk for Disease Progression

ET and pre-PMF are myeloproliferative neoplasms (MPNs) that are each characterized by thrombocytosis but are difficult to distinguish by clinical and histopathological criteria. Moreover, each has the propensity to progress at variable rates to more advanced forms of the disease. The cause of progression to more overt forms of myelofibrosis (MF) or accelerated /blast phase (AP/BP) has yet to be fully understood, making prognostication difficult. To identify patients (pts) who are at risk for disease progression, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and array Comparative Genomic Hybridization + Single Nucleotide Polymorphism (aCGH+SNP) of 158 pts with a diagnosis of ET or pre-PMF from 2017 to 2022 at our institution. Among these pts, 58% were female (92 pts) and 42% were male (66 pts), and the median age was 61 years (range 13-92). Mutational analysis was performed in 155 pts, and JAK2 mutations were present in 63% of cases, CALR in 19%, and MPL in 7% of cases. The remaining 11% of pts were triple negative. An abnormal karyotype was observed in 15% (24/158), and the remaining 85% (134/158) were either normal or had non-diagnostic results due to failed or limited peripheral blood chromosome analysis. Of the 111 pts that had aCGH+SNP testing, 6% (7/111) had prior abnormalities as detected by conventional cytogenetic analyses, while abnormalities were found in 30% (33/111) with aCGH+SNP exclusively. In this cohort, 29% (46/158) of pts underwent disease progression. Among these cases, 65% (30/46) had progression to either MF or chronic myeloid leukemia or myelodysplasia, and 22% (10/46) progressed to AP/BP. In addition, 13% (6/46) evolved to polycythemia vera. Disease progression, irrespective of its form, was associated with genomic alterations detected by aCGH+SNP, cytogenetic analysis, or both at the time of first encounter. Of the 46 pts undergoing progression during their clinical course, 65% (30/46) had an abnormal genomic finding by either technology compared to 35% (16/46) who were normal (p&amp;lt;0.001). Strikingly, among 24 pts who were abnormal by classical cytogenetics, 79% (19/24) progressed to either AP/BP or MF compared to only 20% (26/125) who were cytogenetically normal (p&amp;lt;0.001). As shown in Figure 1, there was a shorter progression-free survival among pts who were cytogenetically abnormal as compared to normal pts (p&amp;lt;0.001). Among 134 pts with ET/pre-PMF who were normal or had non-diagnostic results by classical cytogenetic studies, aCGH+SNP testing was performed in 104 cases and additional genomic aberrations were detected in 32% (33/104). Within this group, 30% (10/33) progressed to MF with a trend towards a shorter progression-free survival. In those patients that progressed to MF, the most frequent abnormality was 9p CNLOH occurring in 6 pts. In the remaining 71 pts that were cytogenetically and aCGH+SNP normal, only 11% (8/71) had disease progression. Overall, the combination of both conventional cytogenetics and aCGH+SNP increased the sensitivity of detecting genomic abnormalities from 15% (cytogenetics alone) to 37% when incorporating aCGH+SNP. These data indicate that genomic alterations detected by conventional cytogenetic analyses or CGH+SNP array identify a subset of ET/pre-PMF pts that are at a higher risk of disease progression.

Time to diagnosis in rapid exome/genome sequencing in the clinical inpatient setting.

Exome and genome sequencing are clinically available, with many laboratories offering expedited testing (e.g., "rapid" and "ultra-rapid"). With the increase in uptake of expedited testing, there is a need for the development of inpatient protocols for best practices based on real-life data. A retrospective 2-year review (October 2019-November 2021) of the utilization of rapid exome and genome sequencing for inpatient cases at a tertiary care center using a utilization management tracking database with subsequent chart review was performed. Thirty-three expedited "rapid/priority" exome/genome tests were performed clinically. The average total turnaround time (TAT) was 17.88 days (5-43 days) with an average TAT of 13.97 days (3-41 days) for the performing laboratory. There were 5 positive diagnostic results (15.2%), 3 likely positive diagnostic results (9%), 2 noncontributory results (6%), and 26 nondiagnostic results (69.7%). Real-life data suggest that there is an approximately 3.91-day lag in getting samples to the performing laboratory. Although laboratories may advertise their expected TAT, a number of factors can potentially impact the actual time from test order placement to communication of the results for clinical use. Understanding the points of delay will enable the development of internal protocols and policies to improve time to diagnosis.

Repeated endoscopic ultrasound-guided fine-needle biopsy of solid pancreatic lesions after previous nondiagnostic or inconclusive sampling.

Repeated endoscopic ultrasound (EUS)-guided tissue acquisition represents the standard practice for solid pancreatic lesions after previous nondiagnostic or inconclusive results. Since data are lacking, we aimed to evaluate the diagnostic performance of repeated EUS fine-needle biopsy (rEUS-FNB) in this setting. The primary outcome was diagnostic accuracy; sample adequacy, sensitivity, specificity, and safety were secondary outcomes. Consecutive patients undergoing rEUS-FNB for solid pancreatic lesions at 23 Italian centers from 2019 to 2021 were retrieved. Pathology on the surgical specimen, malignant histology together with ≥6-month follow-up, and benign pathology together with ≥12-month follow-up were adopted as gold standards. Among 462 patients, 56.5% were male, with a median age of 68 (59-75) years, malignancy prevalence 77.0%. Tumor size was 26 (20-35) mm. Second-generation FNB needles were used in 89.6% cases. Diagnostic accuracy, sensitivity, and specificity of rEUS-FNB were 89.2%, 91.4%, and 81.7%, respectively (19 false-negative and 12 false-positive results). On multivariate analysis, rEUS-FNB performed at high-volume centers (odds ratio [OR] 2.12; 95% confidence interval [CI] 1.10-3.17; P = 0.03) and tumor size (OR 1.03; 95% CI 1.00-1.06; P = 0.05) were independently related to diagnostic accuracy. Sample adequacy was 94.2%. Use of second-generation FNB needles (OR 5.42; 95% CI 2.30-12.77; P < 0.001) and tumor size >23 mm (OR 3.04; 95% CI 1.31-7.06; P = 0.009) were independently related to sample adequacy. Repeated EUS-FNB allowed optimal diagnostic performance after nondiagnostic or inconclusive results. Patients' referral to high-volume centers improved diagnostic accuracy. The use of second-generation FNB needles significantly improved sample adequacy over standard EUS-FNB needles.

Clinical SMN1 and SMN2 Gene-Specific Sequencing to Enhance the Clinical Sensitivity of Spinal Muscular Atrophy Diagnostic Testing

Purpose. Therapeutic advances in the treatment of spinal muscular atrophy (SMA) prompt the need for robust and efficient molecular diagnosis of this disease. Approximately five percent of SMA cases are attributable to one copy of SMN1 with a hypomorphic or inactivating variant in trans with a deleted or converted allele. These intragenic variants are challenging to definitively localize to SMN1 due to its sequence homology with the SMN2 gene. To enhance the clinical sensitivity of SMA diagnostic testing, we present an optimized gene-specific sequencing assay to localize variants to either SMN1 or SMN2. Methods. SMN1 and SMN2 genes are independently amplified by long-range allele-specific PCR. Long-range products are used in subsequent nested PCR reactions to amplify the coding exons of SMN1 and SMN2. The resulting products are sequenced using standard Sanger-based methodologies and analyzed for disease-associated alterations. Results. 83 probands suspicious for a clinical diagnosis of SMA with a nondiagnostic SMN dosage result were sequenced for intragenic variants in the SMN1 gene. Gene-specific sequencing revealed likely disease-associated variants in SMN1 in 42 cases (50.6%). Of the 42 variants, 27 are unique including 16 loss-of-function variants, 9 missense variants, 1 in-frame deletion variant, and 1 splice site variant. Conclusions. Herein, we describe an optimized assay for clinical sequencing of the full coding region of SMN1 and SMN2. This assay uses standard techniques and equipment readily available to most molecular diagnostic laboratories.

Thyroid US-guided FNA techniques: A prospective,randomized controlled study

BackgroundThyroid nodules are common in the general population. Ultrasonography is the most efficient diagnostic approach to evaluate thyroid nodules. The US FNAC procedure can be performed using either the short axis (perpendicular), or a long axis (parallel) approach to visualize the needle as it is advanced toward the desired nodule. The main aim of this study was to compare the percentage of non-diagnostic results between the long and short axis approach. MethodsA prospective study that included a randomized controlled trial and was divided into two arms—the short axis and the long axis—was conducted. A total of 245 thyroid nodules were collected through the fine needle aspiration cytology, performed with ultrasound, from march 2021 to march 2022. The patient's demographic information were collected and also nodules characteristics. ResultsOf 245 nodules sampled, 122 were sampled with the long axis method, while 123 with the short axis method. There is not significantly less non diagnostic approach with either method compared to the other (11.5 % vs 16.3 % respectively). DiscussionPrevious studies came to the conclusion that the long axis method yields fewer non diagnostic samples. This study evaluated the two FNA approaches which were proceeded by the same physician who is expert in both techniques. ConclusionThe US FNAC performed in the long axis approach will not produce more conclusive results and less non diagnostic results (Bethesda category 1) than the short axis approach one.

Binary subclassification scheme (AUS-Nuclear versus AUS-Other) adequately risk-stratifies thyroid fine needle aspiration specimens classified as Atypia of Undetermined Significance

The Bethesda System for Reporting Thyroid Cytopathology previously described 4subclassesof atypia within the Atypia of Undetermined Significance (AUS) category: nuclear (AUS-Nuc), architectural (AUS-A), oncocytic (AUS-Onc), and atypia not otherwise specified (AUS-NOS). Accumulating evidence supports a binary AUS subclassification scheme based primarily on the presence of nuclear atypia only. The purpose of this study is to compare the risk stratification of binary versus 4-tier AUS subclassification systems among AUS nodules with molecular and/or histologic follow-up. Thyroid aspirates classified as AUS and tested using Afirma (Veracyte, Inc.) between 6/2013 and 7/2021 were included. For resected nodules, histological classification was considered as the final outcome. For unresected nodules, benign Afirma results were considered low-risk outcomes, similar to histologically benign nodules. Suspicious or nondiagnostic Afirma results were considered indeterminate outcomes. The prevalence of outcomes warranting surgery (noninvasive follicular thyroid neoplasm with papillary-like nuclear features [NIFTP] or cancer) was calculated for each AUS subclass. A total of 559 AUS nodules with Afirma testing were identified. Excluding nodules with indeterminate molecular outcomes, NIFTP/cancer prevalence for AUS-Nuc was 21% (57/266), which was higher than that for AUS-A (6%, 11/188), AUS-Onc (8%, 4/53), and AUS-NOS (0%, 0/9). A binary AUS subclassification scheme based on nuclear atypia showed a significant difference in NIFTP/cancer prevalence (21% versus 6%, P < 0.0001). Binary reporting of AUS subclasses based on nuclear atypia distinguishes cases with a higher risk of NIFTP/cancer. There is a low but non-negligible prevalence of NIFTP/cancer in cases without nuclear atypia.

Risk Factors for Nondiagnostic Imaging in a Real-World Deployment of Artificial Intelligence Diabetic Retinal Examinations in an Integrated Healthcare System: Maximizing Workflow Efficiency Through Predictive Dilation.

In the pivotal clinical trial that led to Food and Drug Administration De Novo "approval" of the first fully autonomous artificial intelligence (AI) diabetic retinal disease diagnostic system, a reflexive dilation protocol was used. Using real-world deployment data before implementation of reflexive dilation, we identified factors associated with nondiagnostic results. These factors allow a novel predictive dilation workflow, where patients most likely to benefit from pharmacologic dilation are dilated a priori to maximize efficiency and patient satisfaction. Retrospective review of patients who were assessed with autonomous AI at Johns Hopkins Medicine (8/2020 to 5/2021). We constructed a multivariable logistic regression model for nondiagnostic results to compare characteristics of patients with and without diagnostic results, using adjusted odds ratio (aOR). P < .05 was considered statistically significant. Of 241 patients (59% female; median age = 59), 123 (51%) had nondiagnostic results. In multivariable analysis, type 1 diabetes (T1D, aOR = 5.82, 95% confidence interval [CI]: 1.45-23.40, P = .01), smoking (aOR = 2.86, 95% CI: 1.36-5.99, P = .005), and age (every 10-year increase, aOR = 2.12, 95% CI: 1.62-2.77, P < .001) were associated with nondiagnostic results. Following feature elimination, a predictive model was created using T1D, smoking, age, race, sex, and hypertension as inputs. The model showed an area under the receiver-operator characteristics curve of 0.76 in five-fold cross-validation. We used factors associated with nondiagnostic results to design a novel, predictive dilation workflow, where patients most likely to benefit from pharmacologic dilation are dilated a priori. This new workflow has the potential to be more efficient than reflexive dilation, thus maximizing the number of at-risk patients receiving their diabetic retinal examinations.

SAT454 Repetition Of Fine Needle Aspiration Cytology After An Initial Nondiagnostic Result: Does An Optimal Timing Exist?

Abstract Disclosure: I. Cosme: None. E.L. Nobre: None. M.J. Bugalho: None. Background: The optimal time to repeat a fine-needle aspiration cytology (FNAC) of a thyroid nodule, after a nondiagnostic (ND) result, is not established. It has been proposed to wait at least 3 months for a 2nd FNAC, in order to mitigate the possible inflammatory cytological changes induced by a previous FNAC. This study aimed to evaluate whether the time between 2 consecutive FNACs, influences the final cytological result. We analysed the occurrence of ND or atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in the 2nd FNAC, in different repetition time intervals. Methods: Retrospective study (2017-2020) including thyroid nodules with a first ND FNAC, submitted to a 2nd FNAC. All FNACs were ultrasound-guided. Demographic data, time interval between FNACs and their results were collected. The 2nd FNAC results were analysed according to FNACs´ repetition interval. We considered 2 intervals: ≤ vs &amp;gt; 3 months and ≤ vs &amp;gt;6 months after the initial FNAC. The 2nd FNAC results were classified as ND, AUS/FLUS or diagnostic (including the other Bethesda FNAC categories). Results: Included 190 nodules (190 patients, 82.1% women, mean age 60±13.7 years) with a 1st ND FNAC submitted to a 2nd FNAC. The 2nd FNAC result remained ND in 63 cases, was AUS/FLUS in 9 and diagnostic in 118 (benign in 116 cases, follicular neoplasm/suspicious follicular neoplasm in 1 and malignant in 1 case). There were no statistical differences in 2nd FNAC result performed ≤3 months (13 ND, 2 AUS/FLUS, 19 diagnostic) vs &amp;gt;3 months (50 ND, 7 AUS/FLUS, 99 diagnostic) - p=0.71. Considering a wider time interval between FNACs, there were also no statistical differences in the 2nd FNAC result: ≤ 6 months (32 ND, 3 AUS/FLUS, 59 diagnostic) vs &amp;gt;6 months (31 ND, 6 AUS/FLUS, 59 diagnostic) - p=0.61. Conclusions: The time interval between FNACs was not relevant to the final cytological result. Early FNAC repetition did not increase the cases of ND or AUS/FLUS. Presentation: Saturday, June 17, 2023

Diagnostic Yield of Cone-beam-Derived Augmented Fluoroscopy and Ultrathin Bronchoscopy Versus Conventional Navigational Bronchoscopy Techniques.

Pulmonary nodules suspicious for lung cancer are frequently diagnosed. Evaluating and optimizing the diagnostic yield of lung nodule biopsy is critical as innovation in bronchoscopy continues to progress. This is a retrospective cohort study. Consecutive patients undergoing guided bronchoscopy for suspicious pulmonary nodule(s) between February 2020 and July 2021 were included. The cone-beam computed tomography (CBCT)+ radial endobronchial ultrasound (r-EBUS) group had their procedure using CBCT-derived augmented fluoroscopy along with r-EBUS. The CBCT+ ultrathin bronchoscope (UTB)+r-EBUS group had the same procedure but with the use of an ultrathin bronchoscope. The r-EBUS group underwent r-EBUS guidance without CBCT or augmented fluoroscopy. We used multivariable logistic regression to compare diagnostic yield, adjusting for confounding variables. A total of 116 patients were included. The median pulmonary lesion diameter was 19.5mm (interquartile range, 15.0 to 27.5mm), and 91 (78.4%) were in the peripheral half of the lung. Thirty patients (25.9%) underwent CBCT+UTB, 27 (23.3%) CBCT, and 59 (50.9%) r-EBUS alone with unadjusted diagnostic yields of 86.7%, 70.4%, and 42.4%, respectively ( P <0.001). The adjusted diagnostic yields were 85.0% (95% CI, 68.6% to 100%), 68.3% (95% CI, 50.1% to 86.6%), and 44.5% (95% CI, 31.0% to 58.0%), respectively. There was significantly more virtual navigational bronchoscopy use in the r-EBUS group (45.8%) compared with the CBCT+UTB (13.3%) and CBCT (18.5%) groups, respectively. CBCT procedures required dose area product radiation doses of 7602.5µGym 2 . Compared with the r-EBUS group, CBCT + UTB + r-EBUS was associated with higher navigational success, fewer nondiagnostic biopsy results, and a higher diagnostic yield. CBCT procedures are associated with a considerable radiation dose.

Diagnostic value of exercise stress echocardiography on a horizontal cycle ergometer in patients with low-risk non-ST elevation acute coronary syndrome

Aim. To evaluate the diagnostic accuracy of exercise stress echocardiography on a horizontal cycle ergometer for the detection of obstructive coronary artery disease (CAD) in patients with low-risk non-ST-elevation acute coronary syndrome (NSTE-ACS).Material and methods. The study included 95 patients aged 53 (46;63) years (men, 58%), hospitalized in the regional vascular center with low-risk NSTE-ACS. Patients with known CAD, impaired resting left ventricular contractility were not included. During hospitalization, standard stress echocardiography on a horizontal cycle ergometer and invasive or non-invasive coronary angiography (CAG) were performed. All values of coronary obstruction ≥70% were verified by invasive CAG. The assessment of myocardial revascularization was observational.Results. All patients had normal structural and functional cardiac parameters at rest. No adverse events were recorded during the tests. The result of stress echocardiography according to impaired local contractility (ILC) criterion was positive in 9 (16%), negative in 28 (49%), incomplete symptom-limited in 20 (35%) patients. Coronary artery stenosis ≥50%/≥70% was detected in 78/78% of cases in the subgroup with a positive result, in 29/11% — with a negative result, 30/10% — with a non-diagnostic result. The association of ILC with stenosis ≥70% was higher, with an odds ratio of 30,1 (4,9; 186,5) vs 8,5 (1,6; 46,1) for stenosis ≥50%. There were following diagnostic accuracy for stenosis ≥70%: sensitivity — 70%, specificity — 93%, positive predictive value — 78%, negative predictive value — 89%, overall accuracy — 86%.Conclusion. Exercise stress echocardiography on a horizontal cycle ergometer in patients with low-risk NSTE-ACS patients is safe and feasible. The method has moderate sensitivity and positive predictive value and high specificity, negative predictive value and overall accuracy for the detection of anatomically significant coronary artery stenosis. In the structure of results, there is a significant proportion (35%) of symptom-limited tests incomplete due to heart rate, characterized by the lowest incidence of obstructive atherosclerosis.

Reliability of Fine Needle Aspiration Cytology for Salivary Gland Tumours Meta-Analytical Study

Abstract Background Fine needle aspiration (FNA) cytology is a safe, reliable, minimally invasive and cost- effective technique for the diagnosis of salivary gland lesions. Aim and objectives to assess the accuracy, sensitivity and specificity of FNAC for diagnosis of salivary gland tumors in comparison with biopsy as definite diagnostic tool for these tumors. Subjects and methods This is a Retrospective and prospective studies, was carried out on Patients diagnosed with salivary gland tumors, treated with surgical management. Result FNA was associated with statistically significant fewer nondiagnostic results, Pooled analysis of all studies (n = 3605) revealed that rate of nondiagnostic results is 2.992% with 95% CI of rate 91.10–95.09 with absence of publication bias. Conclusion Fine needle aspiration biopsy is an important diagnostic tool for evaluating parotid gland tumors. It is more accurate in detecting benign tumors. In tumors greater than 2 cm and extending to the deep lobe, the sensitivity of fine needle aspiration biopsy is high. The use of fine needle aspiration biopsy in conjunction with clinical and radiological evaluation may help to reduce false positive and false negative results Funding Sources This research received no grant from any funding agency in the public, commercial or not-for-profit sectors.

Deep learning model to predict exercise stress test results: Optimizing the diagnostic test selection strategy and reduce wastage in suspected coronary artery disease patients

BackgroundCardiac exercise stress testing (EST) offers a non-invasive way in the management of patients with suspected coronary artery disease (CAD). However, up to 30% EST results are either inconclusive or non-diagnostic, which results in significant resource wastage. Our aim was to build machine learning (ML) based models, using patients demographic (age, sex) and pre-test clinical information (reason for performing test, medications, blood pressure, heart rate, and resting electrocardiogram), capable of predicting EST results beforehand including those with inconclusive or non-diagnostic results. MethodsA total of 30,710 patients (mean age 54.0 years, 69% male) were included in the study with 25% randomly sampled in the test set, and the remaining samples were split into a train and validation set with a ratio of 9:1. We constructed different ML models from pre-test variables and compared their discriminant power using the area under the receiver operating characteristic curve (AUC). ResultsA network of Oblivious Decision Trees provided the best discriminant power (AUC=0.83, sensitivity=69%, specificity=0.78%) for predicting inconclusive EST results. A total of 2010 inconclusive ESTs were correctly identified in the testing set. ConclusionsOur ML model, developed using demographic and pre-test clinical information, can accurately predict EST results and could be used to identify patients with inconclusive or non-diagnostic results beforehand. Our system could thus be used as a personalised decision support tool by clinicians for optimizing the diagnostic test selection strategy for CAD patients and to reduce healthcare expenditure by reducing nondiagnostic or inconclusive ESTs.

Stimulated Raman histology as a method to determine the adequacy of renal mass biopsy and identify malignant subtypes of renal cell carcinoma.

Renal tumor biopsy requires adequate tissue sampling to aid in the investigation of small renal masses. In some centers the contemporary nondiagnostic renal mass biopsy rate may be as high as 22% and may be as high as 42% in challenging cases. Stimulated Raman Histology (SRH) is a novel microscopic technique which has created the possibility for rapid, label-free, high-resolution images of unprocessed tissue which may beviewed onstandard radiology viewing platforms. The application of SRH to renal biopsy may provide the benefits of routine pathologic evaluation during the procedure, thereby reducing nondiagnostic results. We conducted a pilot feasibility study, to assess if renal cell carcinoma (RCC) subtypes may be imaged and to see if high-quality hematoxylin and eosin (H&E) could subsequently be generated. An 18-gauge core needle biopsy was taken from a series of 25 ex vivo radical or partial nephrectomy specimens. Histologic images of the fresh, unstained biopsy samples were obtained using a SRH microscope using 2 Raman shifts: 2,845 cm-1and 2,930 cm-1. The cores were then processed as per routine pathologic protocols. The SRH images and hematoxylin and eosin (H&E) slides were then viewed by a genitourinary pathologist. The SRH microscope took 8 to 11 minutes to produce high-quality images of the renal biopsies. Total of 25 renal tumors including 1 oncocytoma, 3 chromophobe RCC, 16 clear cells RCC, 4 papillary RCC, and 1 medullary RCC were included. All renal tumor subtypes were captured, and the SRH images were easily differentiated from adjacent normal renal parenchyma. High quality H&E slides were produced from each of the renal biopsies after SRH was completed. Immunostains were performed on selected cases and the staining was not affected by the SRH image process. SRH produces high quality images of all renal cell subtypes that can be rapidly produced and easily interpreted to determine renal mass biopsy adequacy, and on occasion, may allow renal tumor subtype identification. Renal biopsies remained available to produce high quality H&E slides and immunostains for confirmation of diagnosis. Procedural application has promise to decrease the known rate of renal mass nondiagnostic biopsies, and application of convolutional neural network methodology may further improve diagnostic capability and increase utilization of renal mass biopsy among urologists.

Preoperative Diagnosis of Warthin Tumors Combining Cytological, Clinical and Ultrasonographic Information within a Multidisciplinary Approach in a Lump Clinic.

(1) Background: Warthin tumors account for about 20% of all benign salivary tumors, approaching 50% if we consider only the parotid gland. Wait and see is considered a reasonable option, but the diagnosis should be certain. Diagnosis can be based on morphological and cytological data, but the sensitivity of the fine needle aspiration cytology (FNAC) is not absolute, with a high rate of non-diagnostic findings in the event of a Warthin tumor, hindering the counseling and therapeutic decisions. The aim of the study is to evaluate the reliability of FNAC and its combination with anamnestic, clinical, and ultrasonographic data in diagnosing Warthin tumors. (2) Methods: A total of 413 patients affected by masses within the major salivary gland and managed between 2017 and 2022 at our institution have been included in the present retrospective study. Each patient underwent fine needle aspiration biopsy (FNAB) with a subsequent cytological diagnosis; successively, for each patient, the clinician (otolaryngologist) and the histopathologist discussed the combination of cytological (even non-diagnostic), clinical, and ultrasonographic data in order to make a "multiparametric" diagnosis. A total of 214 cases were subsequently submitted to surgical resection and had a final histopathology report, to which the cytological and the multiparametric diagnoses can be compared. We extracted all the patients with a cytological, multiparametric, and/or histological diagnosis of Warthin tumors in order to assess the sensitivity and specificity of FNAC and of multiparametric analysis in diagnosing Warthin tumors in case of a major salivary gland mass. (3) Results: One hundred thirty-two cases had a cytological, multiparametric, and/or histological diagnosis of Warthin tumors. FNAC displays a sensitivity of 68.4% and a specificity of 98.7% in diagnosing Warthin tumors. The multiparametric evaluation allowed a considerable improvement in sensitivity (92.9% vs. 68.4%), minimizing the number of non-diagnostic results and preserving at the same time a similar value of specificity (95.5% vs. 98.7%). Notably, none of the patients with a cytological or multiparametric diagnosis of Warthin were affected by a malignant lesion in the final histopathological report. (4) Conclusions: In the case of Warthin tumors, a multiparametric evaluation encompassing anamnestic, clinical, and cytological data is effective in reducing the number of non-diagnostic reports and can safely guide the management of a tumor (e.g., antibiotic treatment of infectious complications, assign a low priority to surgery, even consider observation avoiding surgery) which is absolutely benign and can be associated with no clinically relevant issues.

#2684 DIAGNOSTIC YIELD OF A TARGETED GENE PANEL FOR MONOGENIC KIDNEY DISEASES: A EUROPEAN STUDY

Abstract Background and Aims Despite advances in understanding the underlying causes of CKD, 20% of cases remain unexplained (1). A genomic approach has the potential to identify the cause of CKD in a significant portion of pediatric and adult patients, with estimated diagnostic rates of 5-30% (2). However, there is a lack of consensus in the scientific community on the best diagnostic algorithm. The DECIDE project (Diagnostic EffiCacy kIdney Disease European) is a European collaboration that aims to address this issue by evaluating the diagnostic rate of a targeted gene panel in a large cohort of patients. Method DECIDE involved three Italian and two Spanish centers, encompassing both pediatric and adult patients. The study used the Nephropathies Solution Panel (NES, SOPHiA Genetics), which covers 44 kidney-related genes, to test patients with a high suspicion of genetic kidney disease. The clinical presentation was classified into cystic disease, glomerulopathy, CAKUT, tubulopathy, nephrocalcinosis, other, and negative phenotype. The diagnostic yield of the NES panel was calculated. To assess the genotype-phenotype relationship, Kaplan-Meier analyses were performed. Additionally, the diagnostic results obtained from alternative technologies, such as larger panels, WES and hybridization arrays, in cases of NES panel negative results, were also collected. Results As far as now the DECIDE project collected 632 genetic data. To evaluate the diagnostic accuracy of the panel, the number of (likely) pathogenic variants correlated to phenotype was analyzed. The diagnostic yield is shown in Figure 1, with 46% for cystic disease, 41% for glomerulopathy, 33% for tubulopathies, 28% for CAKUT, 14% for nephrocalcinosis, 2% for negative (in the context of segregation analyses or in cascade test) and 8% for other. Table 1 shows that the main genes involved in the diagnosis were PKD1, PKD2, COL4A3, COL4A4, and COL4A5. In patients affected by cystic disease, the mean age of kidney failure was 48 years in the presence of diagnostic variants, 59 years for VUS, and no events were reported in patients with negative tests. The Kaplan-Meier curve confirmed a worse prognosis in patients with diagnostic variants (p-value&amp;lt;0.05). However, no significant genotype-phenotype correlation in terms of time to replacement therapy was observed in glomerulopathic patients. In cases of non-diagnostic results, 21 further investigations were performed. An enriched panel for cystic disease didn't detect any diagnostic variants, while only one patient was diagnosed using WES. The Hybridization Array identified a gene deletion that is under investigation and may be related to the phenotype (Nephronophthisis). Conclusion The preliminary results of the DECIDE project, based on about 600 data, demonstrate the potential of the NES panel in the diagnosis of kidney genomic disease. The panel showed a good diagnostic yield for cystic disease (46%) and glomerulopathy (41%), but it appears less effective in other clinical presentations. The average diagnostic yield of the panel was comparable to published data for gene panel and WES approaches. However, additional tests such as larger gene panels, WES, or CGH-array were found to be of limited usefulness, as they only identified one pathogenic variant. These results suggest that new approaches are necessary to uncover the hidden genetic components of rare renal conditions.