Variation of computed tomography-derived extracellular volume fraction and the impact of protocol parameters: A systematic review and meta-analysis.

BACKGROUND: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation. METHODS: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity. RESULTS: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I2 â€‹= â€‹93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates. CONCLUSION: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis.

High mortality in free-ranging wild boars associated with African swine fever virus in India.

The present study focuses on the pathological and molecular characterization of African swine fever virus (ASFV) associated with an outbreak in wild boars in two national parks in southern India in 2022-2023. Significant mortality was observed among free-ranging wild boars at Bandipur National Park, Karnataka, and Mudumalai National Park, Tamil Nadu. Extensive combing operations were undertaken in both national parks, spanning an area of around 100 km2, originating from the reported epicenter, to estimate the mortality rate. Recovered carcasses were pathologically examined, and ASFV isolates was genetically characterized. Our findings suggested spillover infection of ASFV from nearby domestic pigs, and the virus was equally pathogenic in wild boars and domestic pigs. ASFV intrusion was reported in the Northeastern region of the country, which borders China and Myanmar, whereas the current outbreak is very distantly located, in southern India. Molecular data will help in tracing the spread of the virus in the country.

Deciphering the genetic landscape of lumpy skin disease: Unraveling variable virulence through comprehensive genome sequence analysis in India.

Lumpy Skin Disease (LSD), a poxvirus disease affecting cattle, emerged in India in 2019 and intensified in 2022, resulting in significant economic losses for dairy farmers. There was unusual shift in mortality and morbidity patterns during the second wave. A comprehensive genetic study conducted, analyzing samples from 2019 to 2022 revealed circulation of two distinct subclades (subclade 1.2a and 1.2b) in India, with the latter showing a different pattern in morbidity and mortality. Notably, the Ankyrin repeats gene-based analysis could differentiate animals with varying clinical scores. Genetic variations were significant, with unique deletions identified, including a 12-nucleotide deletion in the GPCR gene in virus isolates collected during 2022 outbreaks, not reported earlier in Indian LSDV strains. A crucial finding was a significant 95-nucleotide deletion in the Functional Resolution Sequence (FRS) repeats of LSDV genomes from 2022 outbreaks, absent in 2019 samples. These deletions may have influenced the virus's virulence in India.

MRI-based radiomic features for identifying recurrent prostate cancer after proton radiation therapy.

PURPOSE: Magnetic Resonance Imaging (MRI) evaluation of recurrent prostate cancer (PCa) following proton beam therapy is challenging due to radiation-induced tissue changes. This study aimed to evaluate MRI-based radiomic features so as to identify the recurrent PCa after proton therapy. METHODS: We retrospectively studied 12 patients with biochemical recurrence (BCR) following proton therapy. Two experienced radiologists identified prostate lesions from multi-parametric MRI (mpMRI) images post-proton therapy and marked control regions of interest (ROIs) on the contralateral side of the prostate gland. A total of 210 radiomic features were extracted from lesions and control regions on the T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) image series. Recursive Feature Elimination with Cross-Validation method (RFE-CV) was used for feature selection. A Multilayer Perceptron (MLP) neural network was developed to classify three classes: cancerous, benign, and healthy tissue. The 12-core biopsy results were used as the gold standard for the segmentations. The classifier performance was measured using specificity, sensitivity, the area under receiver operating characteristic curve (AUC), and other statistical indicators. RESULTS: Based on biopsy results, 10 lesions were identified as PCa recurrence while eight lesions were confirmed to be benign. Ten radiomic features (10/210) were selected to build the multi-class classifier. The radiomics classifier gave an accuracy of 0.83 in identifying cancerous, benign, and healthy tissue with a sensitivity of 0.80 and specificity of 0.85. The model yielded an AUC of 0.87, 95% CI [0.72-1.00] in differentiating cancer from the benign and healthy tissues. CONCLUSIONS: Our proof-of-concept study demonstrates the potential of using radiomic features as part of the differential diagnosis of PCa on mpMRI following proton therapy. The results need to be validated in a larger cohort.

A Novel Method of Intraoperative Calculation in Follicular Unit Transplantation: 'The Sequential Strip and FUE Method'.

Hair loss, in particular androgenetic alopecia, has troubled humans since the dawn of history. Treatment options for hair restoration have undergone massive transformation from punch grafting to follicular unit transplantation. Current surgical treatment options in hair restoration fall broadly under two categories, follicular unit transplantation most commonly known as strip method and follicular unit extraction (FUE). The strip method though widely used initially is not so common now due to its fair share of disadvantages ranging from linear donor scar, scar widening to strip overharvesting and wastage of grafts. Follicular unit excision (FUE) was introduced as an alternative method for extraction of grafts to combat the donor linear scar produced by strip method but the disadvantages of FUE include the number of grafts harvested in a single session, moth eaten appearance of donor area caused by over extraction of grafts and harvesting from outside the safe zone. Newer developments like extraction of axillary hair, body hair and pubic hair have been sought to overcome the limitations of number of grafts harvested in a single session of FUE. With more patients now affected by alopecia in their early 20s, there is an ever-increasing demand from the patients for the youthful hairline and hence the focus has shifted towards mega and giga sessions of hair transplantation which pose danger of over extraction of grafts leading to depletion of available donor sites. This article elaborates the combined sequential strip and FUE method along with an intraoperative calculation model to overcome the limitations of over extraction and wastage of grafts. (1) Combination of techniques Strip method with FUE. (2) An intraoperative calculation model that aids in limiting over extraction and wastage of grafts. (3) It is a real time model which can be applied in practice with ease.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Development and evaluation of recombinant gD protein based ELISA for sero-surveillance of BoHV-1 in India.

Bovine herpes virus-1 (BoHV-1) is responsible for production losses through decreased milk yields, abortions, infertility, and trade restrictions in the bovine population. The disease is endemic in many countries including India. As the virus harbors a unique feature of latency animals once infected with the virus remain sero-positive for lifetime and can re-excrete the virus when exposed to stressful conditions. Hence, identification and culling of infected animals is only the means to minimize infection-associated losses. In this study, an economical indigenous assay for the detection of BoHV-1 specific antibodies was developed to cater to the huge bovine population of the country. The viral structural gD protein, expressed in the prokaryotic system was used for optimization of an indirect ELISA for bovines followed by statistical validation of the assay. The diagnostic sensitivity and specificity of the indirect ELISA were 82.9% and 91.3% respectively. Systematically collected serum samples representing organized, unorganized and breeding farms of India were tested with the indigenously developed assay for further validation.

Can magnetic resonance imaging differentiate muscle invasion (T2) and lamina propria invasion (T1) urothelial carcinoma of the bladder? A systematic review and meta-analysis of Vesical Imaging-Reporting and Data System accuracy.

Background: Vesical Imaging-Reporting and Data System (VI-RADS) was developed as a structured reporting tool to anticipate the possibility of muscle invasion. This study is aimed to investigate the diagnostic accuracy of VI-RADS for discriminating T2 from T1 bladder cancer. Materials and methods: Scopus, Web of Science, PubMed, and Embase were searched on October 4, 2021, for studies with the following characteristics: (1) bladder cancer patient population, (2) VI-RADS as an index test, (3) retransurethral resection of bladder tumor/cystectomy as a reference, and (4) adequate VI-RADS score data for T1 and T2 lesions. The analyses were performed using the binary regression model of MIDAS in Stata. Results: Six studies with 624 magnetic resonance imaging reports were included. The receiver operating characteristics curve for differentiation of T2 from T1 bladder cancer showed an area under the curve of 0.93 (95% confidence interval [CI], 0.91-0.95) for a VI-RADS ≥3 and 0.75 (95% CI, 0.71-0.79) for a VI-RADS ≥4. A VI-RADS ≥3 showed high sensitivity of 93% (95% CI, 85%-97%), specificity of 61% (95% CI, 30%-86%), positive likelihood ratio of 2.4 (95% CI, 1.1-5.3), and negative likelihood ratio of 0.11 (95% CI, 0.05-0.24). A total of 10.4% of T2 lesions were scored as VI-RADS 2, while 10% of T1 lesions were scored as VI-RADS 4 or 5. Conclusions: The VI-RADS ≥3 has high accuracy and sensitivity for detecting muscle invasion in borderline populations of T1 or T2 bladder cancer. Thus, the VI-RADS could be a good non-invasive screening test for the detection of T2 urothelial lesions.

Warthin-like papillary carcinoma thyroid.

Solitary thyroid nodule should raise a suspicion of malignancy, which is very common in middle-aged females. Papillary carcinoma thyroid is the most common thyroid malignancy. Warthin-like papillary carcinoma is one of its rare variants. It has a frequent association with Hashimoto's thyroiditis. Here, we report a case of 43-year-old female who presented with swelling in the anterior aspect of neck for 1 month. Fine-needle aspiration cytology features were suggestive of papillary carcinoma thyroid and biopsy confirmed the diagnosis of Warthin-like papillary carcinoma thyroid. This variant is of great clinical and prognostic significance as it carries an excellent prognosis.

Metastatic prostate cancer is associated with distinct higher frequency of genetic mutations at diagnosis.

INTRODUCTION AND OBJECTIVES: We explored characteristic genetic mutations associated with metastatic prostate cancer (PCa) by comparing next generation sequencing (NGS) data between men with or without metastatic disease at diagnosis. METHODS: We queried the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry for men diagnosed with PCa. Patients were categorized into with (M1) or without metastatic disease (M0) groups. The difference in the frequency of genetic mutations between the two groups and the prognostic significance of the mutations were analyzed using SPSS V28. We included frequency rate of > 5% and P values < 0.05 were considered statistically significant to maintain over 95% true positive detection rate. RESULTS: Of a total of 10,580 patients with diagnosis of PCa in the dataset, we selected a study cohort of 1268 patients without missing data; 700 (55.2%) had nonmetastatic PCa, 421 (33.2%) and 147 (11.6%) patients had metastatic castration sensitive and resistant PCa respectively. The median age at diagnosis and serum prostate specific antigen (PSA) level for the entire cohort was 62.8 years (IQR 56.3-68.4) and 8.0 ng/ml (IQR 4.9-20.9) respectively. A vast majority of the cohort were of Caucasian ancestry (89.1%). Of a total of 561 genes sequenced, there were mutations in 79 genes (14.1%). The mutation frequency was significantly higher in M1PCa compared to M0PCa, 35.7% and 23.3%, respectively (P = <0.001). The median tumor mutational burden was also significantly higher in the samples from M1PCa (2.59 mut/MB) compared to M0PCa (1.96 mut/MB) (P < 0.001). Compared to M0PCa patients, M1PCa patients demonstrated significantly higher rate of genetic mutations; TP53 (38.73% vs. 17.71% P < 0.001), PTEN (25.70% vs. 11.71% P < 0.001), AR (17.25% vs. 1.43% P < 0.001), APC (11.8% vs. 4.43% P < 0.001), TMPRSS2 (31.5% vs. 11.14% P < 0.001), ERG (23.59% vs. 13.13% P < 0.001), FOXA1 (17.43% vs. 6.33% P < 0.001), MYC (8.45% vs. 2.29% P < 0.001), RB1 (10.39% vs. 2.43% P < 0.001) and CDK12 (8.45% vs. 1.31% P < 0.001).  Of the various cellular signaling pathways, the androgen receptor signaling pathway was most often impacted. In the cohort with M1 disease, compared to men without genetic mutations the men with genetic mutations demonstrated worse survival (P = <0.001, log rank test). Compared to castration sensitive M1 patients, AR (57% vs. 4% P < 0.001), TP53 (50.7% vs. 34% P < 0.001), PTEN (35.2% vs. 22.1% P < 0.001), RB1(23.9% vs. 4.75% P < 0.001) were significantly more frequently mutated in castration resistant M1 patients. In contrast, mutations of SPOP (13.3% vs. 7.9% P < 0.001), FOXA1 (17.6% vs. 5.3% P < 0.001) and CDK12 (12% vs. 6.45% P < 0.001) were significantly more frequently found in castration sensitive M1 patients compared to castration resistant patients. CONCLUSION: Patients with M1PCa demonstrated characteristic genetic mutations compared to M0PCa, which most often influenced androgen receptor signaling and is associated with worse survival. In addition, we identified distinct genetic mutations between castration sensitive and resistant M1PCa. These findings may be used to further our understanding and management of men with PCa.

A Novel Technique to Convert Static Sling into a Dynamic Sling in Reconstruction of Total Lower Lip Defects Using Palmaris Longus Tendon with Free Radial Forearm Flap and Case Series.

Lower lip reconstruction has been a major challenge for the reconstructive surgeons since time immemorial. Various types of reconstruction had been described for the reconstruction of lower lip ranging from local flaps to free tissue transfer to free functioning muscle transfer. For complete lower lip defects, the free radial forearm flap with palmaris longus tendon has been the standard of reconstruction for many years. Literatures suggests various techniques for utilizing palmaris longus tendon sling as a static as well as dynamic structure. The limitation with static reconstruction is the loss of sling support with time leading to eversion and drooping of the reconstructed lower lip and drooling of saliva. In this article we describe a simpler and novel technique which converts static reconstruction into a dynamic one with a series of 5 patients. Aim of this prospective study was to evaluate the post operative functional and aesthetic outcome of our technique of total lower lip reconstruction using free radial forearm flap with palmaris longus sling reconstruction. The medical records included were demographics, including age, gender, and reason for the acquired defect, lip reconstructed, reconstructive method, flap survival, and outcomes. At 6 months follow up, all patients had satisfactory outcome and were able to take oral diets and none of the patients complained of drooling, an inability to eat in a public setting, or microstomia. This technique which is a simpler modification can be helpful in converting the traditional static sling reconstruction of lower lip into a dynamic one resulting in good aesthetic and functional outcomes.

The Bivalent Bromodomain Inhibitor MT-1 Inhibits Prostate Cancer Growth.

Bromodomains (BD) are epigenetic readers of histone acetylation involved in chromatin remodeling and transcriptional regulation of several genes including protooncogene cellular myelocytomatosis (c-Myc). c-Myc is difficult to target directly by agents due to its disordered alpha helical protein structure and predominant nuclear localization. The epigenetic targeting of c-Myc by BD inhibitors is an attractive therapeutic strategy for prostate cancer (PC) associated with increased c-Myc upregulation with advancing disease. MT-1 is a bivalent BD inhibitor that is 100-fold more potent than the first-in-class BD inhibitor JQ1. MT-1 decreased cell viability and causes cell cycle arrest in G0/G1 phase in castration-sensitive and resistant PC cell lines in a dose-dependent fashion. The inhibition of c-Myc function by MT-1 was molecularly corroborated by the de-repression of Protein Kinase D1 (PrKD) and increased phosphorylation of PrKD substrate proteins: threonine 120, serine 11, and serine 216 amino acid residues in ß-Catenin, snail, and cell division cycle 25c (CDC25c) proteins, respectively. The treatment of 3D cell cultures derived from three unique clinically annotated heavily pretreated patient-derived PC xenografts (PDX) mice models with increasing doses of MT-1 demonstrated the lowest IC50 in tumors with c-Myc amplification and clinically resistant to Docetaxel, Cabazitaxel, Abiraterone, and Enzalutamide. An intraperitoneal injection of either MT-1 or in combination with 3jc48-3, an inhibitor of obligate heterodimerization with MYC-associated protein X (MAX), in mice implanted with orthotopic PC PDX, decreased tumor growth. This is the first pre-clinical study demonstrating potential utility of MT-1 in the treatment of PC with c-Myc dysregulation.

Genetic mutations in smoking-associated prostate cancer.

OBJECTIVES: Tobacco smoking is known to cause cancers potentially predisposed by genetic risks. We compared the frequency of gene mutations using a next generation sequencing database of smokers and nonsmokers with prostate cancer (PCa) to identify subsets of patients with potential genetic risks. MATERIALS AND METHODS: Data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry was analyzed. The GENIE registry contains clinically annotated sequenced tumor samples. We included 1832 men with PCa in our cohort, categorized as smokers and nonsmokers, and compared the frequency of mutations (point mutations, copy number variations, and structural variants) of 47 genes with more than 5% mutation rate between the two categories and correlated with overall survival using logistic regression analysis. RESULTS: Overall, 1007 (55%) patients were nonsmokers, and 825 (45%) were smokers. The mutation frequency was significantly higher in smokers compared to nonsmokers, 47.6% and 41.3%, respectively (p = 0.02). The median tumor mutational burden was also significantly higher in the samples from smokers (3.59 mut/MB) compared to nonsmokers (1.87 mut/MB) (p < 0.001). Patients with a smoking history had a significantly higher frequency of PREX2, PTEN, AGO2, KMT2C, and a lower frequency of adenomatous polyposis coli (APC) and KMT2A mutations than compared to nonsmokers. The overall mortality rate (28.5% vs. 22.8%) was significantly higher among smokers (p = 0.006). On a multivariate logistic regression analysis, the presence of metastatic disease at the time of diagnosis (OR: 2.26, 95% CI: 1.78-2.89, p < 0.001), smoking history (OR: 1.32, 95% CI: 1.05-1.65, p = 0.02), and higher frequency of PTEN somatic gene mutation (OR: 1.89, 95% CI: 1.46-2.45, p < 0.001) were independent predictors of increased overall mortality among patients with PCa. Patients with PTEN mutation had poorer overall survival compared to men without PTEN mutations: 96.00 (95% CI: 65.36-113.98) and 120.00 (95% CI: 115.05-160.00) months, respectively (p < 0.001) irrespective of smoking history although the G129R PTEN mutation was characteristically detected in smokers. CONCLUSIONS: PCa patients with a tobacco smoking history demonstrated a significantly higher frequency of somatic genetic mutations. Whereas mutations of PREX2, KMT2C, AGO2, and PTEN genes were higher in smokers, the APC and KMT2A mutations were higher in nonsmokers. The PTEN somatic gene mutation was associated with increased overall mortality among patients with PCa irrespective of smoking history. We found that G129R PTEN mutation known to reduce the PTEN phosphatase activity and K267Rfs*9 a frameshift deletion mutation in the C2 domain of PTEN associated with membrane binding exclusively detected in smokers and nonsmokers, respectively. These findings may be used to further our understanding of PCa associated with smoking.

Urinary stone disease burden is increased in patients with cognitive impairment.

Mental illness and brain disorders such as dementia are commonly encountered in patients with cognitive impairment in urology. In this cohort study, we assessed the prevalence and outcomes of inpatient admissions for stone disease in patients with cognitive impairment. Using the National Inpatient Sample database, we identified adults (>18 years) with stone disease between 2015 and 2019. The patients were dichotomized based on the presence or absence of cognitive impairment. The groups were compared for baseline differences in inpatient admissions and hospital complications. We evaluated the independent factors associated with urinary complications in the population using multivariate logistic regression. We identified 223,072 patients with stone disease. Patients with cognitive impairment were significantly (P<0.001) older (68 vs. 62 years), female (55.7% vs. 47.4%), had government-issued insurance (77.5% vs. 64.4%), and were discharged to a nursing facility (31.7% vs. 14.2%). Patients with cognitive impairment had significantly higher rates of urinary tract infection (29.7% vs. 21.5%, P<0.001), pneumonia (5.6% vs. 4.6%, P<0.001), systemic sepsis (4.3% vs. 3.8%, P<0.001), and acute renal failure (0.9% vs. 0.7%, P = 0.008). Female sex, low income, and cognitive impairment were all independently more likely to experience a urinary complication, with significant differences (P<0.001). Patients with cognitive impairment have a higher prevalence of stone disease and urinary complications associated with inpatient admissions than the rest of the population. Health care inequities among cognitively impaired patients should be a topic of further study.

Interleukin-1ß Disruption Protects Male Mice From Heart Failure With Preserved Ejection Fraction Pathogenesis.

Background Heart failure with preserved ejection fraction (HFpEF) is a significant unmet need in cardiovascular medicine and remains an untreatable cardiovascular disease. The role and mechanism of interleukin-1ß in HFpEF pathogenesis are poorly understood. Methods and Results C57/Bl6J and interleukin-1ß-/- male mice were randomly divided into 4 groups. Groups 1 and 2: C57/Bl6J and interleukin-1ß-/- mice were fed a regular diet for 4 months and considered controls. Groups 3 and 4: C57/Bl6 and interleukin-1ß-/- mice were fed a high-fat diet with N[w]-nitro-l-arginine methyl ester (endothelial nitric oxide synthase inhibitor, 0.5 g/L) in the drinking water for 4 months. We measured body weight, blood pressure, diabetes status, cardiac function/hypertrophy/inflammation, fibrosis, vascular endothelial function, and signaling. C57/Bl6 fed a high-fat diet and N[w]-nitro-l-arginine methyl ester in the drinking water for 4 months developed HFpEF pathogenesis characterized by obesity, diabetes, hypertension, cardiac hypertrophy, lung edema, low running performance, macrovascular and microvascular endothelial dysfunction, and diastolic cardiac dysfunction but no change in cardiac ejection fraction compared with control mice. Interestingly, the genetic disruption of interleukin-1ß protected mice from HFpEF pathogenesis through the modulation of the inflammation and endoplasmic reticulum stress mechanisms. Conclusions Our data suggest that interleukin-1ß is a critical driver in the development of HFpEF pathogenesis, likely through regulating inflammation and endoplasmic reticulum stress pathways. Our findings provide a potential therapeutic target for HFpEF treatment.

Cardiac Computed Tomography for Quantification of Myocardial Extracellular Volume Fraction: A Systematic Review and Meta-Analysis.

BACKGROUND: Extracellular volume (ECV) is a quantitative measure of extracellular compartment expansion, and an increase in ECV is a marker of myocardial fibrosis. Although cardiac magnetic resonance (CMR) is considered the standard imaging tool for ECV quantification, cardiac computed tomography (CT) has also been used for ECV assessment. OBJECTIVES: The aim of this meta-analysis was to evaluate the correlation and agreement in the quantification of myocardial ECV by CT and CMR. METHODS: PubMed and Web of Science were searched for relevant publications reporting on the use of CT for ECV quantification compared with CMR as the reference standard. The authors employed a meta-analysis using the restricted maximum-likelihood estimator with a random-effects method to estimate summary correlation and mean difference. A subgroup analysis was performed to compare the correlation and mean differences between single-energy CT (SECT) and dual-energy CT (DECT) techniques for the ECV quantification. RESULTS: Of 435 papers, 13 studies comprising 383 patients were identified. The mean age range was 57.3 to 82 years, and 65% of patients were male. Overall, there was an excellent correlation between CT-derived ECV and CMR-derived ECV (mean: 0.90 [95% CI: 0.86-0.95]). The pooled mean difference between CT and CMR was 0.96% (95% CI: 0.14%-1.78%). Seven studies reported correlation values using SECT, and 4 studies reported those using DECT. The pooled correlation from studies utilizing DECT for ECV quantification was significantly higher compared with those with SECT (mean: 0.94 [95% CI: 0.91-0.98] vs 0.87 [95% CI: 0.80-0.94], respectively; P = 0.01). There was no significant difference in pooled mean differences between SECT vs DECT (P = 0.85). CONCLUSIONS: CT-derived ECV showed an excellent correlation and mean difference of <1% with CMR-derived ECV. However, the overall quality of the included studies was low, and larger, prospective studies are needed to examine the accuracy and diagnostic and prognostic utility of CT-derived ECV.

The impact of socioeconomic status on the survival of men with early-onset prostate cancer.

Prostate cancer (PCa) is generally considered a disease of older men; however, about 10% of new diagnoses in the US occur in men ≤ 55 years old. Socioeconomic status (SES) has been shown to influence survival in patients with PCa; however, the impact of SES on men with early-onset PCa remains undescribed. Using the National Cancer Database, we identified adult men ≤ 55 years of age with a diagnosis of prostatic adenocarcinoma between 2004-2018. Descriptive statistics were used to characterize differences among different SES groups. Kaplan-Meier (KM) and Cox regression analyses were used to assess the effect of SES on overall survival (OS). A total of 112,563 young patients with PCa with a median follow-up of 79.0 months were identified. Compared to high SES patients, low SES patients were more likely to be African American (42.4% vs. 8.6%; P<0.001), Hispanic (9.5% vs. 2.7%; P<0.001), and uninsured (5.2% vs. 1.1%; P<0.001); they were also more likely to live in a rural area (3.2% vs. 0.1%; P<0.001) and have stage IV disease (5.5% vs. 3.1%; P<0.001). KM analysis showed that a decreasing SES was directly associated with lower rates of OS (log-rank test P<0.001). On multivariable analysis, SES was found to have a negative effect on OS (low SES vs. high SES; hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.41-1.68; P<0.001). In patients with early-onset PCa, SES was associated with lower OS. SES may be considered when implementing programs to improve the management of patients with early-onset PCa.

Extramural venous invasion: a novel magnetic resonance imaging biomarker for adverse pathology in bladder cancer.

Extramural venous invasion (EMVI) recognized on magnetic resonance imaging (MRI) is an unequivocal biomarker for detecting adverse outcomes in rectal cancer: however it has not yet been explored in the area of bladder cancer. In this study, we assessed the feasibility of identifying EMVI findings on MRI in patients with bladder cancer and its avail in identifying adverse pathology. In this single-institution retrospective study, the MRI findings inclusive of EMVI was described in patients with bladder cancer that had available imaging between January 2018 and June 2020. Patient demographic and clinical information were retrieved from our electronic medical records system. Histopathologic features frequently associated with poor outcomes including lymphovascular invasion (LVI), variant histology, muscle invasive bladder cancer (MIBC), and extravesical disease (EV) were compared to MRI-EMVI. A total of 38 patients were enrolled in the study, with a median age of 73 years (range 50-101), 76% were male and 23% were females. EMVI was identified in 23 (62%) patients. There was a significant association between EMVI and MIBC (OR = 5.30, CI = 1.11-25.36; P = 0.036), and extravesical disease (OR = 17.77, CI = 2.37-133; P = 0.005). We found a higher probability of presence of LVI and histologic variant in patients with EMVI. EMVI had a sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 90%, 73%, 94% and 63% respectively in detecting extravesical disease. Our study suggests, EMVI may be a useful biomarker in bladder cancer imaging, is associated with adverse pathology, and could be potentially integrated in the standard of care with regards to MRI reporting systems. A larger study sample size is further warranted to assess feasibility and applicability.

Soft tissue displacement for detection of left ventricle apical dyskinesis with transthoracic echocardiography.

We tested the hypothesis that the use of outward displacement of the soft tissue between the apex and the chest wall as seen in TTE, is a sign of apical displacement and would allow for more accurate diagnosis of apical dyskinesis. This is a retrospective study of 123 patients who underwent TTE and cardiac magnetic resonance imaging (MRI) within a time frame of 6 months between 2008 and 2019. 110 subjects were deemed to have good quality studies and included in the final analysis. An observer blinded to the study objectives evaluated the echocardiograms and recorded the presence or absence of apical dyskinesis. Two independent observers evaluated the echocardiograms based on the presence or absence of outward displacement of the overlying tissue at the LV apex. Cardiac MRI was used to validate the presence of apical dyskinesis. The proportion of studies which were identified as having apical dyskinesis with conventional criteria defined as outward movement of the left ventricular apex during systole were compared to those deemed to have dyskinesis based on tissue displacement. By cardiac MRI, 90 patients had apical dyskinesis. Using conventional criteria on TTE interpretation, 21 were diagnosed with apical dyskinesis (23.3%). However, when soft tissue displacement was used as the diagnostic marker of dyskinesis, 78 patients (86.7%) were diagnosed with dyskinesis, p < 0.01. Detection of displacement of soft tissue overlying the LV apex facilitates better recognition of LV apical dyskinesis.

MRI-based nomograms and radiomics in presurgical prediction of extraprostatic extension in prostate cancer: a systematic review.

PURPOSE: Prediction of extraprostatic extension (EPE) is essential for accurate surgical planning in prostate cancer (PCa). Radiomics based on magnetic resonance imaging (MRI) has shown potential to predict EPE. We aimed to evaluate studies proposing MRI-based nomograms and radiomics for EPE prediction and assess the quality of current radiomics literature. METHODS: We used PubMed, EMBASE, and SCOPUS databases to find related articles using synonyms for MRI radiomics and nomograms to predict EPE. Two co-authors scored the quality of radiomics literature using the Radiomics Quality Score (RQS). Inter-rater agreement was measured using the intraclass correlation coefficient (ICC) from total RQS scores. We analyzed the characteristic s of the studies and used ANOVAs to associate the area under the curve (AUC) to sample size, clinical and imaging variables, and RQS scores. RESULTS: We identified 33 studies-22 nomograms and 11 radiomics analyses. The mean AUC for nomogram articles was 0.783, and no significant associations were found between AUC and sample size, clinical variables, or number of imaging variables. For radiomics articles, there were significant associations between number of lesions and AUC (p < 0.013). The average RQS total score was 15.91/36 (44%). Through the radiomics operation, segmentation of region-of-interest, selection of features, and model building resulted in a broader range of results. The qualities the studies lacked most were phantom tests for scanner variabilities, temporal variability, external validation datasets, prospective designs, cost-effectiveness analysis, and open science. CONCLUSION: Utilizing MRI-based radiomics to predict EPE in PCa patients demonstrates promising outcomes. However, quality improvement and standardization of radiomics workflow are needed.

Potential role for protein kinase D inhibitors in prostate cancer.

Protein kinase D (PrKD), a novel serine-threonine kinase, belongs to a family of calcium calmodulin kinases that consists of three isoforms: PrKD1, PrKD2, and PrKD3. The PrKD isoforms play a major role in pathologic processes such as cardiac hypertrophy and cancer progression. The charter member of the family, PrKD1, is the most extensively studied isoform. PrKD play a dual role as both a proto-oncogene and a tumor suppressor depending on the cellular context. The duplicity of PrKD can be highlighted in advanced prostate cancer (PCa) where expression of PrKD1 is suppressed whereas the expressions of PrKD2 and PrKD3 are upregulated to aid in cancer progression. As understanding of the PrKD signaling pathways has been better elucidated, interest has been garnered in the development of PrKD inhibitors. The broad-spectrum kinase inhibitor staurosporine acts as a potent PrKD inhibitor and is the most well-known; however, several other novel and more specific PrKD inhibitors have been developed over the last two decades. While there is tremendous potential for PrKD inhibitors to be used in a clinical setting, none has progressed beyond preclinical trials due to a variety of challenges. In this review, we focus on PrKD signaling in PCa and the potential role of PrKD inhibitors therein, and explore the possible clinical outcomes based on known function and expression of PrKD isoforms at different stages of PCa.