Understanding YTHDF2-mediated mRNA degradation by m6A-BERT-Deg.

N6-methyladenosine (m6A) is the most abundant mRNA modification within mammalian cells, holding pivotal significance in the regulation of mRNA stability, translation and splicing. Furthermore, it plays a critical role in the regulation of RNA degradation by primarily recruiting the YTHDF2 reader protein. However, the selective regulation of mRNA decay of the m6A-methylated mRNA through YTHDF2 binding is poorly understood. To improve our understanding, we developed m6A-BERT-Deg, a BERT model adapted for predicting YTHDF2-mediated degradation of m6A-methylated mRNAs. We meticulously assembled a high-quality training dataset by integrating multiple data sources for the HeLa cell line. To overcome the limitation of small training samples, we employed a pre-training-fine-tuning strategy by first performing a self-supervised pre-training of the model on 427 760 unlabeled m6A site sequences. The test results demonstrated the importance of this pre-training strategy in enabling m6A-BERT-Deg to outperform other benchmark models. We further conducted a comprehensive model interpretation and revealed a surprising finding that the presence of co-factors in proximity to m6A sites may disrupt YTHDF2-mediated mRNA degradation, subsequently enhancing mRNA stability. We also extended our analyses to the HEK293 cell line, shedding light on the context-dependent YTHDF2-mediated mRNA degradation.

Association between class III obesity and overall survival in previously untreated younger patients with acute myeloid leukemia enrolled on SWOG S1203.

There has been ongoing debate on the association between obesity and outcomes in acute myeloid leukemia (AML). Currently there are few studies that have stratified outcomes by class I obesity, class II obesity, and class III obesity; and a more nuanced understanding is becoming increasingly important with the rising prevalence of obesity. We examined the association between body mass index (BMI) and outcomes in previously untreated AML in younger patients (age ≤60) enrolled in SWOG S1203 (n=729). Class III obesity was associated with an increased rate of early death (p=0.004) and worse overall survival (OS) in multivariate analysis (hazard ratio (HR) 2.48, 95% confidence interval (CI) 1.62-3.80 versus normal weight). Class III obesity was also associated with worse OS after allogeneic hematopoietic cell transplant (HR 2.37, 95% CI 1.24-4.54 versus normal weight). These findings highlight the unique risk of class III obesity in AML, and the importance of further investigation to better characterize this patient population.

Congenital Cataracts with Thin Lenses (Leptophakia) in Children: Morphology and Surgical Outcomes.

PURPOSE: To describe the morphology and postoperative outcomes of pediatric cataracts with thin (leptophakic) lenses. DESIGN: Retrospective comparative clinical cohort study. METHODS: We identified the records of pediatric patients who had undergone cataract surgery between 2018-2023 and lens thickness less than two standard deviations of age-stratified normal eyes in the general population. Matching controls were identified based on sex, age at surgery, and intraocular lens implant status. Data abstracted include axial length, anterior chamber depth, lens thickness, visual acuity, intraocular pressure, and surgical details. RESULTS: A total of 13 eyes from seven patients were identified to be leptophakic, 8 of which had matching controls. Compared to the control eyes, leptophakic eyes had thinner lenses (2.74 ± 0.39 mm vs 4.82 ± 1.01 mm, p < 0.01) with comparable anterior chamber depth (3.28 ± 0.76 mm vs 2.98 ± 1.28 mm, p = 0.13) and axial lengths (19.17 ± 2.61 mm vs 20.76 ± 1.76 mm, p = 0.20). Following cataract surgery, visual acuity improved for both the leptophakic and control cohorts within 2.5 months postoperatively (-0.68 ± 0.37 LogMAR vs -0.06 ± 0.42 LogMAR, p = 0.03) and at 1-2 years postoperatively (-1.58 ± 1.03 LogMAR vs -0.60 ± 0.49 LogMAR, p = 0.22) without any glaucoma-related adverse events. Of note, 5 of 13 leptophakic eyes (38%) were found to have posterior capsular ruptures intraoperatively. CONCLUSIONS: Leptophakic eyes demonstrated similar intraoperative and short-term postoperative outcomes when compared to control eyes, though vigilance for posterior capsular defects and ruptures may be necessary.

Sex and HIV Differences in Preserved Ratio Impaired Spirometry (PRISm) Among Ugandans Postpneumonia.

Background: Preserved ratio impaired spirometry (PRISm), defined as a normal ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (≥0.70) with low FEV1 (<80% predicted), has been associated with increased mortality in the general population. Female sex has been associated with increased odds of PRISm in people without HIV. People with HIV (PWH) are at increased risk for lung function abnormalities, but whether HIV modifies the effect of sex on PRISm development is largely unknown. Methods: Adults with and without HIV underwent baseline followed by serial spirometry after completing therapy for pneumonia, predominantly tuberculosis (TB), in Kampala, Uganda. Using generalized estimating equations adjusted for age, body mass index, smoking, biomass fuel exposure, HIV, and TB status, we compared individuals with PRISm with those with normal spirometry. These models were stratified by HIV status. Results: Of 339 baseline participants, 153 (45%) were women; 129 (38%) had HIV, of whom 53% were women. Overall, 105/339 participants (31%) had PRISm at baseline. HIV was associated with lower odds of PRISm (adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.68; P = .001). Female sex trended toward increased odds of PRISm among all participants (aOR, 1.65; 95% CI, 0.99-2.75; P = .052). The association between female sex and PRISm tended to be stronger among PWH (aOR, 3.16; 95% CI, 1.14-8.76; P = .03) than among those without HIV (aOR, 1.34; 95% CI, 0.73-2.45; P = .34); this study was underpowered to detect an HIV-sex interaction of this magnitude (P = .30). Conclusions: Among Ugandan adults who recovered from pneumonia, female sex was associated with increased odds and HIV with decreased odds of PRISm, suggesting independent sex and HIV effects on PRISm pathogenesis.

Understanding YTHDF2-mediated mRNA Degradation By m6A-BERT-Deg.

N6-methyladenosine (m6A) is the most abundant mRNA modification within mammalian cells, holding pivotal significance in the regulation of mRNA stability, translation, and splicing. Furthermore, it plays a critical role in the regulation of RNA degradation by primarily recruiting the YTHDF2 reader protein. However, the selective regulation of mRNA decay of the m6A-methylated mRNA through YTHDF2 binding is poorly understood. To improve our understanding, we developed m6A-BERT-Deg, a BERT model adapted for predicting YTHDF2-mediated degradation of m6A-methylated mRNAs. We meticulously assembled a high-quality training dataset by integrating multiple data sources for the HeLa cell line. To overcome the limitation of small training samples, we employed a pre-training-fine-tuning strategy by first performing a self-supervised pre-training of the model on 427,760 unlabeled m6A site sequences. The test results demonstrated the importance of this pre-training strategy in enabling m6A-BERT-Deg to outperform other benchmark models. We further conducted a comprehensive model interpretation and revealed a surprising finding that the presence of co-factors in proximity to m6A sites may disrupt YTHDF2-mediated mRNA degradation, subsequently enhancing mRNA stability. We also extended our analyses to the HEK293 cell line, shedding light on the context-dependent YTHDF2-mediated mRNA degradation.

Combined hepatic resection and ablation for high burden of colorectal liver metastases demonstrates safety and durable survival.

BACKGROUND: Hepatic resection (HR) and thermal ablation of Colorectal Liver Metastases (CRLM) have each individually demonstrated safety and survival benefit. We sought to provide our experience with the combination of HR + ablation within one operation for patients with multiple CRLM. METHODS: Review of a single institution database of patients who underwent HR + ablation between 2010 and 2019. RESULTS: 161 patients were identified who underwent HR + ablation for isolated CRLM (mean age: 59, male 63.4%). 125 (77.6%) patients had bilobar disease and 92 (57.1%) patients had ≥5 tumors. 28 (17.4%) patients experienced minor (grade 1 or 2) complications while 20 (12.4%) had grade 3-5 complications. Patients who underwent simultaneous colon resection with HR + ablation had a higher complication rate (22 of 47, 46.8%) than those undergoing HR + ablation only (26 of 114, 22.8%, p = 0.002). Median and 5-year OS for all patients undergoing HR + ablation was 38.2 months and 33.2%, respectively. 5-year hepatic recurrence free survival was 23.5%. Patients with 5 or more tumors demonstrated no difference in median survival compared to those with fewer than 5 tumors (37.0 months vs 38.4 months, p = 0.326). CONCLUSIONS: In this population of CRLM patients with a relatively high burden of disease, HR + ablation demonstrated an acceptable safety profile as well as durable long-term survival.

Duration of intermittent hypoxia impacts metabolic outcomes and severity of murine NAFLD.

Rationale: Obstructive sleep apnea (OSA) is associated with metabolic dysfunction, including progression of nonalcoholic fatty liver disease (NAFLD). Chronic intermittent hypoxia (IH) as a model of OSA worsens hepatic steatosis and fibrosis in rodents with diet induced obesity. However, IH also causes weight loss, thus complicating attempts to co-model OSA and NAFLD. We sought to determine the effect of various durations of IH exposure on metabolic and liver-related outcomes in a murine NAFLD model. We hypothesized that longer IH duration would worsen the NAFLD phenotype. Methods: Male C57BL/6J mice (n = 32) were fed a high trans-fat diet for 24 weeks, to induce NAFLD with severe steatohepatitis. Mice were exposed to an IH profile modeling severe OSA, for variable durations (0, 6, 12, or 18 weeks). Intraperitoneal glucose tolerance test was measured at baseline and at six-week intervals. Liver triglycerides, collagen and other markers of NAFLD were measured at sacrifice. Results: Mice exposed to IH for 12 weeks gained less weight (p = 0.023), and had lower liver weight (p = 0.008) relative to room air controls. These effects were not observed in the other IH groups. IH of longer duration transiently worsened glucose tolerance, but this effect was not seen in the groups exposed to shorter durations of IH. IH exposure for 12 or 18 weeks exacerbated liver fibrosis, with the largest increase in hepatic collagen observed in mice exposed to IH for 12 weeks. Discussion: Duration of IH significantly impacts clinically relevant outcomes in a NAFLD model, including body weight, fasting glucose, glucose tolerance, and liver fibrosis.

Effects of Everolimus in Modulating the Host Immune Responses against Mycobacterium tuberculosis Infection.

The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (P13K/AKT/mTOR) pathway plays a key role in tuberculosis (TB) pathogenesis and infection. While the activity levels of this pathway during active infection are still debated, manipulating this pathway shows potential benefit for host-directed therapies. Some studies indicate that pathway inhibitors may have potential for TB treatment through upregulation of autophagy, while other studies do not encourage the use of these inhibitors due to possible host tissue destruction by Mycobacterium tuberculosis (M. tb) and increased infection risk. Investigating further clinical trials and their use of pathway inhibitors is necessary in order to ascertain their potential for TB treatment. This paper is particularly focused on the drug everolimus, an mTOR inhibitor. One of the first clinical trials sponsored by the Aurum Institute showed potential benefit in using everolimus as an adjunctive therapy for tuberculosis. Infection with tuberculosis is associated with a metabolic shift from oxidative phosphorylation towards glycolysis. The everolimus arm in the clinical trial showed further reduction than the control for both maximal and peak glycolytic activity. Compared with control, those receiving everolimus demonstrated increased lung function through forced expiratory volume in 1 s (FEV1) measurements, suggesting that everolimus may mitigate inflammation contributing to lung damage.

Tumor microenvironment in a minipig model of spinal cord glioma.

BACKGROUND: Spinal cord glioma (SCG) is considered an orphan disease that lacks effective treatment options with margins that are surgically inaccessible and an overall paucity of literature on the topic. The tumor microenvironment is a critical factor to consider in treatment and modeling design, especially with respect to the unresectable tumor edge. Recently, our group developed a high-grade spinal cord glioma (SCG) model in Göttingen minipigs. METHODS: Immunofluorescence and ELISA were performed to explore the microenvironmental features and inflammation cytokines in this minipig SCG model. Protein carbonyl assay and GSH/GSSG assay were analyzed in the core and edge lesions in the minipig SCG model. The primary core and edge cells proliferation rate were shown in vitro, and the xenograft model in vivo. RESULTS: We identified an elevated Ki-67 proliferative index, vascular and pericyte markers, CD31 and desmin in the tumor edge as compared to the tumor core. In addition, we found that the tumor edge demonstrated increased pro-inflammatory and gliomagenic cytokines including TNF-α, IL-1ß, and IL-6. Furthermore, the mediation of oxidative stress is upregulated in the tumor edge. Hypoxic markers had statistically significant increased staining in the tumor core, but were notably still present in the tumor edge. The edge cells cultures derived from SCG biopsy also demonstrated an increased proliferative rate compared to core cell cultures in a xenotransplantation model. CONCLUSIONS: Our study demonstrates heterogeneity in microenvironmental features in our minipig model of high-grade SCG, with a phenotype at the edge showing increased oxidative stress, proliferation, inflammatory cytokines, neovascularization, and decreased but present staining for hypoxic markers. These findings support the utility of this model as a means for investigating therapeutic approaches targeting the more aggressive and surgically unresectable tumor border.

Isolated abnormal diffusing capacity for carbon monoxide (iso↓DLco) is associated with increased respiratory symptom burden in people with HIV infection.

OBJECTIVES: An isolated reduction in the diffusing capacity for carbon monoxide (DLco; iso↓DLco) is one of the most common pulmonary function test (PFT) abnormalities in people living with HIV (PWH), but its clinical implications are incompletely understood. In this study, we explored whether iso↓DLco in PWH is associated with a greater respiratory symptom burden. STUDY DESIGN: Cross-sectional analysis. METHODS: We used ATS/ERS compliant PFTs from PWH with normal spirometry (post-bronchodilator FEV1/FVC ≥0.7; FEV1, FVC ≥80% predicted) from the I AM OLD cohort in San Francisco, CA and Seattle, WA, grouped by DLco categorized as normal (DLco ≥lower limit of normal, LLN), mild iso↓DLco (LLN >DLco >60% predicted), and moderate-severe iso↓DLco (DLco ≤60% predicted). We performed multivariable analyses to test for associations between DLco and validated symptom-severity and quality of life questionnaires, including the modified Medical Research Council dyspnea scale (mMRC), the COPD Assessment Test (CAT), and St. George's Respiratory Questionnaire (SGRQ), as well as between DLco and individual CAT symptoms. RESULTS: Mild iso↓DLco was associated only with a significantly higher SGRQ score. Moderate-severe iso↓DLco was associated with significantly higher odds of mMRC ≥2 and significantly higher CAT and SGRQ scores. PWH with moderate-severe iso↓DLco had increased odds of breathlessness, decreased activity, lower confidence leaving home, and less energy. CONCLUSIONS: Iso↓DLco is associated with worse respiratory symptom scores, and this association becomes stronger with worsening DLco, suggesting that impaired gas exchange alone has a significant negative impact on the quality of life in PWH. Additional studies are ongoing to understand the etiology of this finding and design appropriate interventions.

Practical Tips for Reporting Adnexal Lesions Using O-RADS MRI.

The Ovarian-Adnexal Reporting and Data System (O-RADS) MRI risk stratification system provides a standardized lexicon and evidence-based risk score for evaluation of adnexal lesions. The goals of the lexicon and risk score are to improve report quality and communication between radiologists and clinicians, reduce variability in the reporting language, and optimize management of adnexal lesions. The O-RADS MRI risk score is based on the presence or absence of specific imaging features, including the lipid content, enhancing solid tissue, number of loculi, and fluid type. The probability of malignancy ranges from less than 0.5% when there are benign features to approximately 90% when there is solid tissue with a high-risk time-intensity curve. This information can aid in optimizing management of patients with adnexal lesions. The authors present an algorithmic approach to the O-RADS MRI risk stratification system and highlight key teaching points and common pitfalls. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Imaging of breast cancer-beyond the basics.

Imaging of breast cancer is the backbone of breast cancer screening, diagnosis, preoperative/treatment assessment and follow-up. The main modalities are mammography, ultrasound and magnetic resonance imaging, each with its own advantages and disadvantages. New emerging technologies have also enabled each modality to improve on their weaknesses. Imaging-guided biopsies have allowed for accurate diagnosis of breast cancer, with low complication rates. The purpose of this article is to review the common modalities for breast cancer imaging in current practice with emphasis on the strengths and potential weaknesses, discuss the selection of the best imaging modality for the specific clinical question or patient population, and explore new technologies / future directions of breast cancer imaging.

Sex modifies the risk of HIV-associated obstructive lung disease in Ugandans postpneumonia.

OBJECTIVES: Spirometric abnormalities are frequent, and obstructive lung disease (OLD) is a common comorbidity among people with HIV (PWH). HIV increases the risk of many comorbidities to a greater degree in women than in men. Few studies have evaluated whether sex modifies the HIV-associated risk of OLD. DESIGN AND METHODS: To evaluate the associations between sex and HIV with abnormal lung function, women and men with and without HIV underwent spirometric testing after completing therapy for pneumonia, including tuberculosis (TB), in Kampala, Uganda. OLD was defined as a postbronchodilator forced expiratory volume in the first second to forced vital capacity (FEV 1 /FVC) ratio less than 0.70. Associations between sex, HIV, and lung function were evaluated using multivariable regression models including sex-by-HIV interaction terms after adjusting for age, BMI, smoking status, and TB status. RESULTS: Among 348 participants, 147 (42%) were women and 135 (39%) were HIV-positive. Sixteen (11%) women and 23 men (11%) had OLD. The HIV-sex interaction was significant for obstructive lung disease ( P  = 0.04). In the adjusted stratified analysis, women with HIV had 3.44 (95% CI 1.11-12.0; P  = 0.04) increased odds of having OLD compared with men with HIV. Women without HIV did not have increased odds of having OLD compared with men without HIV. CONCLUSION: HIV appears to increase the risk of OLD to a greater degree in women than in men in an urban Ugandan setting. The mechanistic explanation for this interaction by sex remains unclear and warrants further study.

Spatial Transcriptomics Identifies Expression Signatures Specific to Lacrimal Gland Adenoid Cystic Carcinoma Cells.

Although primary tumors of the lacrimal gland are rare, adenoid cystic carcinoma (ACC) is the most common and lethal epithelial lacrimal gland malignancy. Traditional management of lacrimal gland adenoid cystic carcinoma (LGACC) involves the removal of the eye and surrounding socket contents, followed by chemoradiation. Even with this radical treatment, the 10-year survival rate for LGACC is 20% given the propensity for recurrence and metastasis. Due to the rarity of LGACC, its pathobiology is not well-understood, leading to difficulties in diagnosis, treatment, and effective management. Here, we integrate bulk RNA sequencing (RNA-seq) and spatial transcriptomics to identify a specific LGACC gene signature that can inform novel targeted therapies. Of the 3499 differentially expressed genes identified by bulk RNA-seq, the results of our spatial transcriptomic analysis reveal 15 upregulated and 12 downregulated genes that specifically arise from LGACC cells, whereas fibroblasts, reactive fibrotic tissue, and nervous and skeletal muscle account for the remaining bulk RNA-seq signature. In light of the analysis, we identified a transitional state cell or stem cell cluster. The results of the pathway analysis identified the upregulation of PI3K-Akt signaling, IL-17 signaling, and multiple other cancer pathways. This study provides insights into the molecular and cellular landscape of LGACC, which can inform new, targeted therapies to improve patient outcomes.

AI-Based Automated Lipomatous Tumor Segmentation in MR Images: Ensemble Solution to Heterogeneous Data.

Deep learning (DL) has been proposed to automate image segmentation and provide accuracy, consistency, and efficiency. Accurate segmentation of lipomatous tumors (LTs) is critical for correct tumor radiomics analysis and localization. The major challenge of this task is data heterogeneity, including tumor morphological characteristics and multicenter scanning protocols. To mitigate the issue, we aimed to develop a DL-based Super Learner (SL) ensemble framework with different data correction and normalization methods. Pathologically proven LTs on pre-operative T1-weighted/proton-density MR images of 185 patients were manually segmented. The LTs were categorized by tumor locations as distal upper limb (DUL), distal lower limb (DLL), proximal upper limb (PUL), proximal lower limb (PLL), or Trunk (T) and grouped by 80%/9%/11% for training, validation and testing. Six configurations of correction/normalization were applied to data for fivefold-cross-validation trainings, resulting in 30 base learners (BLs). A SL was obtained from the BLs by optimizing SL weights. The performance was evaluated by dice-similarity-coefficient (DSC), sensitivity, specificity, and Hausdorff distance (HD95). For predictions of the BLs, the average DSC, sensitivity, and specificity from the testing data were 0.72 [Formula: see text] 0.16, 0.73 [Formula: see text] 0.168, and 0.99 [Formula: see text] 0.012, respectively, while for SL predictions were 0.80 [Formula: see text] 0.184, 0.78 [Formula: see text] 0.193, and 1.00 [Formula: see text] 0.010. The average HD95 of the BLs were 11.5 (DUL), 23.2 (DLL), 25.9 (PUL), 32.1 (PLL), and 47.9 (T) mm, whereas of SL were 1.7, 8.4, 15.9, 2.2, and 36.6 mm, respectively. The proposed method could improve the segmentation accuracy and mitigate the performance instability and data heterogeneity aiding the differential diagnosis of LTs in real clinical situations.

Poor post-induction outcomes in patients with acute myeloid leukemia previously treated with hypomethylating agents.

Patients with acute myeloid leukemia (AML) who have failed hypomethylating agents (HMA) have a poor prognosis. We examined whether high intensity induction chemotherapy could abrogate negative outcomes in 270 patients with AML or other high-grade myeloid neoplasms. Prior HMA therapy was significantly associated with a lower overall survival (OS) as compared to a reference group of patients with secondary disease without prior HMA therapy (median 7.2 vs 13.1 months). In patients with prior HMA therapy, high intensity induction was associated with a non-significant trend toward longer OS (median 8.2 vs 4.8 months) and decreased rates of treatment failure (39% vs 64%). These results redemonstrate poor outcomes in patients with prior HMA and suggest possible benefit of high intensity induction that should be evaluated in future studies.

Association between history of childbirth and chronic, functionally significant back pain in later life.

BACKGROUND: Back pain is more prevalent among women than men. The association with sex could be related to pregnancy and childbirth, unique female conditions. This association has not been thoroughly evaluated. METHODS: Using a retrospective cohort design, we evaluated the relationship between history of childbirth on the prevalence and severity of functionally consequential back pain in 1069 women from a tertiary care pain management clinic. Interactions among preexisting, acute peripartum, and subsequent back pain were evaluated as secondary outcomes among the parous women using logistic and linear regression as appropriate. RESULTS: The women who had given birth had a higher risk for functionally significant back pain compared to women who had not given birth (85% vs 77%, p < 0.001, Risk Ratio 1.11 [1.04-1.17]). The association was preserved after correction for age, weight, and race. Back pain was also more slightly severe (Numerical Rating Score for Pain 7[5-8] vs 6[5-7] out of 10, p = 0.002). Women who recalled severe, acute postpartum back pain had a higher prevalence of current debilitating back pain (89% vs 75%, Risk Ratio 1.19 (1.08-1.31), p = 0.001). Twenty-eight percent of acute postpartum back pain never resolved and 40% reported incomplete resolution. CONCLUSIONS: A history of pregnancy and childbirth is a risk factor for chronic functionally significant back pain in women. Severe acute postpartum back pain is a risk factor for future disability suggesting that the peripartum period may provide an important opportunity for intervention. Early recognition and management may mitigate future disability. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov as "Association Between Chronic Headache and Back Pain with Childbirth" (NCT04091321) on 16/09/2019 before it was initiated.

Osteolytic sarcoidosis of the orbit without pulmonary involvement.

A 69-year-old woman with a history of a left orbital mass presented to the emergency room with progressive breakthrough pain in her left orbit despite medical therapy. On examination, there was extraocular motility restriction with diplopia upon left supraduction. Computed tomography (CT) scan of the orbits revealed soft tissue thickening of the left medial and superior periorbita and left lacrimal fossa; bony erosion of the left frontal bone, left orbital roof, and left lamina papyracea; and bilateral mass-like enlargement of the extraocular muscles. An orbitotomy with incisional biopsy was performed, and histopathological examination revealed non-caseating granulomatous inflammation consistent with sarcoidosis. Chest imaging demonstrated no sequela of pulmonary sarcoidosis, and her serum angiotensin converting enzyme (ACE) level was within normal range. She was treated with high-dose oral steroids with resolution of her symptoms. Her pain returned at the conclusion of the steroid taper, and it was controlled with chronic subcutaneous methotrexate and adalimumab injections.

MRI of Adenomyosis: Where Are We Today?

Purpose of Review: The purpose of this review is to (i) summarize the current literature regarding the role of magnetic resonance imaging (MRI) in diagnosing adenomyosis, (ii) examine how to integrate MRI phenotypes with clinical symptomatology and histological findings, (iii) review recent advances including proposed MRI classifications, (iv) discuss challenges and pitfalls of diagnosing adenomyosis, and (v) outline the future role of MRI in promoting a better understanding of the pathogenesis, diagnosis, and treatment options for patients with uterine adenomyosis. Recent Findings: Recent advances and the widespread use of MRI have provided new insights into adenomyosis and the range of imaging phenotypes encountered in this disorder. Summary: Direct and indirect MRI features allow for accurate non-invasive diagnosis of adenomyosis. Adenomyosis is a complex and poorly understood disorder with variable MRI phenotypes that may be correlated with different pathogeneses, clinical presentations, and patient outcomes. MRI is useful for the assessment of the extent of findings, to evaluate for concomitant gynecological conditions, and potentially can help with the selection and implementation of therapeutic options. Nevertheless, important gaps in knowledge remain. This is in part due to the lack of standardized criteria for reporting resulting in heterogeneous and conflicting data in the literature. Thus, there is an urgent need for a unified MRI reporting system incorporating standardized terminology for diagnosing adenomyosis and defining the various phenotypes.

CT-based Bosniak classification of cystic renal lesions: is version 2019 an improvement on version 2005?

OBJECTIVE: To compare the diagnostic performance and inter-reader agreement of the CT-based v2019 versus v2005 Bosniak classification systems for risk stratification of cystic renal lesions (CRL). METHODS: This retrospective study included adult patients with CRL identified on CT scan between 2005 and 2018. The reference standard was histopathology or a minimum 4-year imaging follow-up. The studies were reviewed independently by five readers (three senior, two junior), blinded to pathology results and imaging follow-up, who assigned Bosniak categories based on the 2005 and 2019 versions. Diagnostic performance of v2005 and v2019 Bosniak classifications for distinguishing benign from malignant lesions was calculated by dichotomizing CRL into the potential for ablative therapy (III-IV) or conservative management (I-IIF). Inter-reader agreement was calculated using Light's Kappa. RESULTS: One hundred thirty-nine patients with 149 CRL (33 malignant) were included. v2005 and v2019 Bosniak classifications achieved similar diagnostic performance with a sensitivity of 91% vs 91% and a specificity of 89% vs 88%, respectively. Inter-reader agreement for overall Bosniak category assignment was substantial for v2005 (κ = 0.78) and v2019 (κ = 0.75) between senior readers but decreased for v2019 when the Bosniak classification was dichotomized to conservative management (I-IIF) or ablative therapy (III-IV) (0.80 vs 0.71, respectively). For v2019, wall thickness was the morphological feature with the poorest inter-reader agreement (κ = 0.43 and 0.18 for senior and junior readers, respectively). CONCLUSION: No significant improvement in diagnostic performance and inter-reader agreement was shown between v2005 and v2019. The observed decrease in inter-reader agreement in v2019 when dichotomized according to management strategy may reflect the more stringent morphological criteria. KEY POINTS: • Versions 2005 and 2019 Bosniak classifications achieved similar diagnostic performance, but the specificity of higher risk categories (III and IV) was not increased while one malignant lesion was downgraded to v2019 Bosniak category II (i.e., not subjected to further follow-up). • Inter-reader agreement was similar between v2005 and v2019 but moderately decreased for v2019 when the Bosniak classification was dichotomized according to the potential need for ablative therapies (I-II-IIF vs III-IV).