First Baby Born in Brazil after Simultaneous Diagnosis through Non-Invasive and Conventional PGT-A

Non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) aiming to assess cell-free embryonic DNA in spent culture media is promising, especially because it might overcome the diminished rates of implantation caused by the inadequate performance of trophectoderm (TE) biopsy. Our center is part of the largest study to date assessing the concordance between conventional PGT-A and niPGT-A, and we report here the delivery of the first baby born in Brazil using niPGT-A. The parents of the baby were admitted to our center in 2018. They did not present history of infertility, and they were interested in using in vitro fertilization (IVF) and PGT-A in order to avoid congenital anomalies in the offspring. A total of 11 (3 day-5 and 8 day-6) expanded blastocysts were biopsied, and the spent culture media (culture from day-4 to day-6) from 8 day-6 blastocysts were collected for niPGT-A. Overall, 7 embryos yielded informative results for trophectoderm (TE) and media samples. Among the embryos with informative results, 5 presented concordant diagnosis between conventional PGT-A and niPGT-A, and 2 presented discordant diagnosis (1 false-positive and one false-negative). The Blastocyst 4, diagnosed as 46, XY by both niPGT-A and conventional PGT-A, was warmed up and transferred, resulting in the birth of a healthy 3.8 kg boy in February 2020. Based on our results and the recent literature, we believe that the safest current application of niPGT-A would be as a method of embryo selection for patients without an indication for conventional PGT-A. The approximate 80% of reliability of niPGT-A in the diagnosis of ploidy is superior to predictions provided by other non-invasive approaches like morphology and morphokinetics selection.

Accuracy of Pathologic Diagnosis in Patients With Lymphoma and Survival: A Prospective Analysis From Botswana

PURPOSE With intense HIV epidemics, southern African countries have a high burden of classic Hodgkin lymphoma (CHL) and non-Hodgkin lymphoma (NHL). However, suboptimal access to pathology resources limits subtype classification. We sought to assess the diagnostic accuracy of specimens classified as lymphoma and to determine association between discordant pathologic diagnosis and overall survival. METHODS Seventy patients with CHL or NHL and treated at three Botswana hospitals from 2010 to 2016 were analyzed. Local pathologic assessment relied primarily on morphology. All cases underwent secondary US hematopathology review, which is considered gold standard. RESULTS The median follow-up was 58 months. The overall reclassification rate was 20 of 70 cases (29%). All 20 CHL cases were correctly classified in Botswana, and mixed cellularity was the most common subtype, diagnosed in 11 (55%) cases. Of 47 confirmed NHL cases, diffuse large B-cell lymphoma was the final US diagnosis in 28 cases (60%), another aggressive B-cell NHL in nine (19%), an indolent B-cell NHL in six (13%), and T-cell NHL in four (9%). Common types of diagnostic discordance included NHL subtype reclassification (11 of 20, 55%) and CHL reclassified as NHL (7 of 20, 35%). Concordant versus discordant diagnosis after secondary review was associated with improved 5-year overall survival (60.1% v 26.3%, P = .0066). Discordant diagnosis was independently associated with increased risk of death (adjusted hazard ratio 2.733; 95% CI, 1.102 to 6.775; P = .0300) even after stratifying results by CHL versus NHL. CONCLUSION In this single prospective cohort, discordant pathologic diagnosis was associated with a nearly three-fold increased risk of death. Limited access to relatively basic diagnostic techniques impairs treatment decisions and leads to poor patient outcomes in low-resource countries.

Radiological pitfalls associated with the diagnosis of usual interstitial pneumonia pattern on high-resolution computed tomography and associated findings: experience from a single Italian center

Background The diagnostic algorithm for idiopathic pulmonary fibrosis (IPF) based on high-resolution computed tomography (HRCT) findings and multidisciplinary discussion (MDD) has been well established. Purpose To identify the causes of disagreement between non-thoracic and thoracic radiologist involved in MDD for the imaging diagnosis of usual interstitial pneumonia (UIP) patterns and associated findings on HRCT and to improve the understanding of IPF by non-expert radiologists through a more systematic approach to HRCT. Material and Methods This study included 68 patients who underwent MDD for suspected IPF. We compared the first reports generated before MDD by non-expert radiologists with the CT pattern and associated findings of IPF reported by thoracic radiologist involved in MDD. Results Regarding the diagnosis of CT pattern by non-expert radiologists, 30/68 patients received a discordant diagnosis, and in another 28 reports, all features of the CT pattern were described without reaching a diagnostic conclusion. The first report was concordant in only 10 patients. For 63 cases in which associated findings were reported by expert radiologists in MDD, we documented discrepancies in 47 cases where associated findings were considered absent by the first non-thoracic radiologist. Conclusion We found significant discrepancies in the imaging diagnosis of UIP patterns and associated findings on HRCT between non-expert and thoracic radiologists included in MDD. Therefore, in this study, we analyzed and suggested diagnostic strategies to improve non-expert radiologists’ approach to HRCT.

Comparison of Instantaneous Wave-Free Ratio (iFR) and Fractional Flow Reserve (FFR) with respect to Their Sensitivities to Cardiovascular Factors: A Computational Model-Based Study

While coronary revascularization strategies guided by instantaneous wave-free ratio (iFR) are, in general, noninferior to those guided by fractional flow reserve (FFR) with respect to the rate of major adverse cardiac events at one-year follow-up in patients with stable angina or an acute coronary syndrome, the overall accuracy of diagnosis with iFR in large patient cohorts is about 80% compared with the diagnosis with FFR. So far, it remains incompletely understood what factors contribute to the discordant diagnosis between iFR and FFR. In this study, a computational method was used to systemically investigate the respective effects of various cardiovascular factors on FFR and iFR. The results showed that deterioration in aortic valve disease (e.g., regurgitation or stenosis) led to a marked decrease in iFR and a mild increase in FFR given fixed severity of coronary artery stenosis and that increasing coronary microvascular resistance caused a considerable increase in both iFR and FFR, but the degree of increase in iFR was lower than that in FFR. These findings suggest that there is a high probability of discordant diagnosis between iFR and FFR in patients with severe aortic valve disease or coronary microcirculation dysfunction.

Clinical characteristics, diagnosis, and risk stratification of pulmonary hypertension in severe tricuspid regurgitation and implications for transcatheter tricuspid valve repair

Aims Patients with pulmonary hypertension (PHT) are often excluded from surgical therapies for tricuspid regurgitation (TR). Transcatheter tricuspid valve repair (TTVR) with the MitraClip™ technique is a novel treatment option for these patients. We aimed to assess the role of PHT in severe TR and its implications for TTVR. Methods and results A total of 243 patients underwent TTVR at two centres. One hundred twenty-one patients were grouped as iPHT+ [invasive systolic pulmonary artery pressures (PAPs) ≥50 mmHg]. Patients were similarly stratified according to echocardiographic PAPs (ePHT). The occurrence of the combined clinical endpoint (death, heart failure hospitalization, and reintervention) was investigated during a follow-up of 330 (interquartile range 175–402) days. iPHT+ patients were at higher preoperative risk (P < 0.01), had more severe symptoms (P = 0.01), higher N-terminal pro-B-type natriuretic peptide levels (P < 0.01), more impaired right ventricular (RV) function (P < 0.01), and afterload corrected RV function (P < 0.01). Procedural TTVR success was similar in iPHT+ and iPHT− patients (84 vs. 84%, P = 0.99). The echocardiographic diagnostic accuracy to detect iPHT was only 55%. During follow-up, 35% of patients reached the combined clinical endpoint. The discordant diagnosis of iPHT+/ePHT− carried the highest risk for the combined clinical endpoint [HR 3.76 (CI 2.25–6.37), P < 0.01], while iPHT+/ePHT+ patients had a similar survival-free time from the combined endpoint compared to iPHT− patients (P = 0.48). In patients with isolated tricuspid procedure (n = 131) a discordant iPHT+/ePHT− diagnosis and an impaired afterload corrected RV function (P < 0.01 for both) were independent predictors for the occurrence of the combined endpoint. Conclusion The discordant echocardiographic and invasive diagnosis of PHT in severe TR predicts outcomes after TTVR.

Cost Analysis of Routine Examination of Pathology Specimens Following Ankle Arthroscopy

Background: Routine submission of pathologic specimens for histologic analysis following orthopedic surgery is a common and often required practice in the United States. Prior orthopedic studies have determined that these histologic examinations are of limited cost effectiveness and low clinical value because rarely do the pathology findings alter patient management. The purpose of this study was to evaluate the cost effectiveness and clinical significance of routine histologic examination of tissue specimens removed during ankle arthroscopy. Methods: Between 2014 and 2018, 408 patients underwent ankle arthroscopy at a multi-center hospital system by 16 different orthopedic surgeons. The available pathology reports from these cases were retrospectively reviewed to determine if the routine histologic examination altered patient care. We compared the preoperative diagnosis to both the postoperative and histologic diagnoses. The total cost for these histologic examinations was estimated using 2017 Medicare physician fees released by the College of American Pathologists. Cost-effectiveness was estimated in 2017 US dollars by cost per discrepant and discordant diagnosis. Results: Of the 408 patients who underwent ankle arthroscopy, 361 pathology reports were available for review. The prevalence of concordant diagnosis was 98.9% (357/361); the prevalence of discrepant diagnoses was 1.0% (4/361). There were no cases identified with a discordant diagnosis. Total estimated cost for all pathology specimens was $46 381 in 2017 US dollars. Cost per discrepant diagnosis was $11 595. Conclusion: In our study, histologic examination of surgical specimens following ankle arthroscopy had no effect on patient management, yet it increased costs. Routine examination of these pathologic specimens had a low rate of discrepant and/or discordant diagnoses. Based on our results, routine pathologic examination of ankle arthroscopy tissue specimens should be sent solely at the discretion of the orthopedic surgeon as opposed to being a mandated policy. Level of Evidence: Level IV, case series.

How to diagnose renal artery stenosis correctly using ultrasound? Evaluation of results of renal arteries duplex ultrasonography examinations

Aim: Renal artery duplex ultrasonography (RDU) is an effective and non-invasive screening test in diagnosing renal artery stenosis. The discordance of results in multiple RDU is common. We aim to evaluate the discordance and the reasons for discordance between diagnoses and measurements from multiple RDU examinations.Material and method: A retrospective study was performed in 64 examinations of renal arteries from 32 patients that were referred for two or more RDU examinations and renal artery digital subtraction angiography (DSA) within six months, between August 2013 and January 2016. Using DSA as gold standard, we divided the renal arteries into three groups: discordant (one diagnosis of RDU was correct and one was wrong), misdiagnosed (neither RDU diagnosis was correct) and correct (both RDU diagnoses were correct) groups.We evaluated the discordance and reasons for discordance of diagnoses and measurements from multiple RDU examinations. Results: Among 64 renal arteries included in this study, 37 renal arteries had two correct diagnoses, 19 renal arteries had two discordant diagnoses, and eight renal arteries were misdiagnosed twice by RDU. The discordance of peak systolic velocity (PSV), the ratio between PSV in the renal artery with stenosis and PSV in the aorta (RAR), and tardus-parvus waveform measurements were clearly higher in the discordant diagnoses group than in the correctly diagnosed group. The most common reason for a discordant diagnosis was failure in obtaining correct tardus-parvus waveforms of the interlobar artery (26.31%). Themost common reason for misdiagnosis was the presence of an extremely severe stenosis with an atrophic kidney (31.25%). Overall, 87.50% of patients underwent RDU examinations had correct diagnoses of stenosis or occlusion at least once (including location and degree), as confirmed by DSA.Conclusions: Our study indicates that standard operating procedures and improvements in examination technique by ultrasound doctors could reduce the discordance between multiple tests.

Discordant Diagnosis of Malaria in a Family of Child Refugees from Sierra Leone

The clinical presentation and diagnosis of malaria involving a family with seven children who arrived in Canada as refugees is reported. Discrepancies in front-line testing using microscopy and rapid diagnostic tests compared with confirmatory testing using real-time polymerase chain reaction in this cluster of symptomatic and asymptomatic patients were identified.