Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families

Despite large sequencing and data sharing efforts, previously characterized pathogenic variants only account for a fraction of Mendelian disease patients, which highlights the need for accurate identification and interpretation of novel variants. In a large Mendelian cohort of 4577 molecularly characterized families, numerous scenarios in which variant identification and interpretation can be challenging are encountered. We describe categories of challenges that cover the phenotype (e.g. novel allelic disorders), pedigree structure (e.g. imprinting disorders masquerading as autosomal recessive phenotypes), positional mapping (e.g. double recombination events abrogating candidate autozygous intervals), gene (e.g. novel gene-disease assertion) and variant (e.g. complex compound inheritance). Overall, we estimate a probability of 34.3% for encountering at least one of these challenges. Importantly, our data show that by only addressing non-sequencing-based challenges, around 71% increase in the diagnostic yield can be expected. Indeed, by applying these lessons to a cohort of 314 cases with negative clinical exome or genome reports, we could identify the likely causal variant in 54.5%. Our work highlights the need to have a thorough approach to undiagnosed diseases by considering a wide range of challenges rather than a narrow focus on sequencing technologies. It is hoped that by sharing this experience, the yield of undiagnosed disease programs globally can be improved

Precision Mapping of Intrahepatic Biliary Anatomy and Its Anatomical Variants Having a Normal Liver Using 2D and 3D MRCP

Despite significant advances in hepatobiliary surgery, biliary injury and leakage remain typical postoperative complications. Thus, a precise depiction of the intrahepatic biliary anatomy and anatomical variant is crucial in preoperative evaluation. This study aimed to evaluate the precision of 2D and 3D magnetic resonance cholangiopancreatography (MRCP) in exact mapping of intrahepatic biliary anatomy and its variants anatomically in subjects with normal liver using intraoperative cholangiography (IOC) as a reference standard. Thirty-five subjects with normal liver activity were imaged via IOC and 3D MRCP. The findings were compared and statistically analyzed. Type I was observed in 23 subjects using IOC and 22 using MRCP. Type II was evident in 4 subjects via IOC and 6 via MRCP. Type III was observed equally by both modalities (4 subjects). Both modalities observed type IV in 3 subjects. The unclassified type was observed in a single subject via IOC and was missed in 3D MRCP. Accurate detection by MRCP of intrahepatic biliary anatomy and its anatomical variants was made in 33 subjects out of 35, with an accuracy of 94.3% and a sensitivity of 100%. In the remaining two subjects, MRCP results provided a false-positive pattern of trifurcation. MRCP competently maps the standard biliary anatomy

Magnetic Resonance Imaging Features of Rhino-Orbito-Cerebral Mucormycosis in Post-COVID-19 Patients: Radio-Pathological Correlation

There has been a notable increase in rhino-orbito-cerebral mucormycosis (ROCM) post-coronavirus disease 2019 (COVID-19), which is an invasive fungal infection with a fatal outcome. Magnetic resonance imaging (MRI) is a valuable tool for early diagnosis of ROCM and assists in the proper management of these cases. This study aimed to describe the characteristic MRI findings of ROCM in post-COVID-19 patients to help in the early diagnosis and management of these patients. This retrospective descriptive study was conducted at a single hospital and included 52 patients with COVID-19 and a histopathologically proven ROCM infection who were referred for an MRI of the paranasal sinuses (PNS) due to sino-orbital manifestations. Two radiologists reviewed all the MR images in consensus. The diagnosis was confirmed by histopathological examination. The maxillary sinus was the most commonly affected PNS (96.2%). In most patients (57.7%), multiple sinuses were involved with the black turbinate sign on postcontrast images. Extrasinus was evident in 43 patients with orbital involvement. The pterygopalatine fossa was involved in four patients. Three patients had cavernous sinus extension, two had pachymeningeal enhancement, and one had epidural collection. The alveolar margin was affected in two patients, and five patients had an extension to the cheek. The awareness of radiologists by the characteristic MRI features of ROCM in post-COVID-19 patients helps in early detection, early proper management, and prevention of morbid complications

Advanced strain elastography is a reliable approach for prostate cancer detection in patients with elevated PSA levels

Abstract This study aimed to examine the validity and reproducibility of strain elastography (SE) for detecting prostate cancer (PCa) in patients with elevated prostate-specific antigen (PSA) levels. The study included 107 patients with elevated PSA levels. All eligible patients underwent transrectal ultrasound (TRUS) with real-time elastography (RTE) to detect suspicious lesions. Two readers independently evaluated the lesions and assigned a strain ratio and elastography score to each lesion. Histopathology was used as a reference standard to estimate the validity of RTE in predicting malignant lesions. An intraclass correlation (ICC) was performed to detect reliability of the strain ratios and elastography scores. TRUS-guided biopsy detected malignancies in 64 (59.8%) patients. TRUS with RTE revealed 122 lesions. The strain ratio index (SRI) cut-off values to diagnose malignancy were 4.05 and 4.35, with sensitivity, specificity, and accuracy of 94.7%, 91.3%, and 93.4%, respectively. An elastography score > 3 was the best cut-off value for detecting malignancy. According to readers, the sensitivity, specificity, and accuracy were 91.3–94.7%, 89.5–93.4%, and 91.3–90.9%, respectively. Excellent inter-reader agreement was recorded for SRI and elastography scores, with ICC of 0.937 and 0.800, respectively. SE proves to be an efficient tool for detecting PCa with high accuracy in patients with elevated PSA levels