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Ultrasonic techniques are being developed to detect changes in cancellous bone caused by osteoporosis. The goal of this study was to test the relative in vivo performance of eight backscatter parameters developed over the last several years for ultrasonic bone assessment: apparent integrated backscatter (AIB), frequency slope of apparent backscatter (FSAB), frequency intercept of apparent backscatter (FIAB), normalized mean of the backscatter difference (nMBD), normalized slope of the backscatter difference (nSBD), normalized intercept of the backscatter difference (nIBD), normalized backscatter amplitude ratio (nBAR) and backscatter amplitude decay constant (BADC). Backscatter measurements were performed on the left and right femoral necks of 80 adult volunteers (age = 25 ± 11 y) using an imaging system equipped with a convex array transducer. For comparison, additional ultrasonic measurements were performed at the left and right heel using a commercially available heel-bone ultrasonometer that measured the stiffness index. Six of the eight backscatter parameters (all but nSBD and nIBD) exhibited similar and highly significant (p0.000001) left-right correlations (0.51 ≤ R ≤ 0.68), indicating sensitivity to naturally occurring variations in bone tissue. Left-right correlations for the stiffness index measured at the heel (R = 0.75) were not significantly better than those produced by AIB, FSAB and FIAB. The short-term precisions of AIB, nMBD, nBAR and BADC (7.8%-11.7%) were comparable to that of the stiffness index measured with the heel-bone ultrasonometer (7.5%).

Aims: There is strong evidence that cribriform morphology indicates a worse prognosis of prostatic adenocarcinoma. Our aim was to investigate its interobserver reproducibility in prostate needle biopsies. Methods and results: A panel of nine prostate pathology experts from five continents independently reviewed 304 digitised biopsies for cribriform cancer according to recent International Society of Urological Pathology criteria. The biopsies were collected from a series of 702 biopsies that were reviewed by one of the panellists for enrichment of high-grade cancer and potentially cribriform structures. A 2/3 consensus diagnosis of cribriform and noncribriform cancer was reached in 90% (272/304) of the biopsies with a mean kappa value of 0.56 (95% confidence interval 0.52–0.61). The prevalence of consensus cribriform cancers was estimated to 4%, 12%, 21%, and 20% of Gleason scores 7 (3 + 4), 7 (4 + 3), 8, and 9–10, respectively. More than two cribriform structures per level or a largest cribriform mass with ≥9 lumina or a diameter of ≥0.5 mm predicted a consensus diagnosis of cribriform cancer in 88% (70/80), 84% (87/103), and 90% (56/62), respectively, and noncribriform cancer in 3% (2/80), 5% (5/103), and 2% (1/62), respectively (all P < 0.01). Conclusion: Cribriform prostate cancer was seen in a minority of needle biopsies with high-grade cancer. Stringent diagnostic criteria enabled the identification of cribriform patterns and the generation of a large set of consensus cases for standardisation. publishedVersion

Purpose:Multiparametric magnetic resonance imaging (mpMRI) fails to identify some men with significant prostate cancer. Prostate-specific membrane antigen positron emission tomography/computerized ...

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3–G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

Background: Active surveillance (AS) mitigates harms from overtreatment of low-risk prostate lesions. Recalibration of diagnostic thresholds to redefine which prostate lesions are considered "cancer" and/or adopting alternative diagnostic labels could increase AS uptake and continuation. Methods: We searched PubMed and EMBASE to October 2021 for evidence on: (1) clinical outcomes of AS, (2) subclinical prostate cancer at autopsy, (3) reproducibility of histopathological diagnosis, and (4) diagnostic drift. Evidence is presented via narrative synthesis. Results: AS: one systematic review (13 studies) of men undergoing AS found that prostate cancer-specific mortality was 0%-6% at 15 years. There was eventual termination of AS and conversion to treatment in 45%-66% of men. Four additional cohort studies reported very low rates of metastasis (0%-2.1%) and prostate cancer-specific mortality (0%-0.1%) over follow-up to 15 years. Overall, AS was terminated without medical indication in 1%-9% of men. Subclinical reservoir: 1 systematic review (29 studies) estimated that the subclinical cancer prevalence was 5% at 79 years. Four additional autopsy studies (mean age: 54-72 years) reported prevalences of 12%-43%. Reproducibility: 1 recent well-conducted study found high reproducibility for low-risk prostate cancer diagnosis, but this was more variable in 7 other studies. Diagnostic drift: 4 studies provided consistent evidence of diagnostic drift, with the most recent (published 2020) reporting that 66% of cases were upgraded and 3% were downgraded when using contemporary diagnostic criteria compared to original diagnoses (1985-1995) Conclusions: Evidence collated may inform discussion of diagnostic changes for low-risk prostate lesions.

Gout is a form of arthritis, resulting from an inflammatory reaction to the deposition of monosodium urate (MSU) crystals in the synovial fluid of the joint space. It is characterised by periods of acute inflammation in the affected joint, or joints (known as gout flares), separated by asymptomatic periods. There seems to be substantial overlap between environmental triggers of gout flares and common environmental modifiers (diet, pharmaceuticals, and stress) of epigenetic markers (DNA methylation, histone modifications, and ncRNA). Very few studies have looked at whether environment is influencing gout through epigenetic mechanisms. The pathogenesis of gouty inflammation is well understood but understanding the variation of response to hyperuricaemia in terms of gout flare initiation is less well known. In this review, we will examine the potential of epigenomics in understanding how gout flares may occur, both in terms of development of hyperuricaemia and the inflammatory response. Looking at the epigenome and its intersection with lifestyle could help identify new targets and strategies for effective management of gout flares.

Objective To prospectively investigate the condition-specific health-related quality of life (HRQoL) of athletes six months and one-year following sport-related concussion. Design Prospective, longitudinal study. Setting Clinical research centre at university school of public health. Participants Amateur athletes who were diagnosed with sport-related concussion within one-week after presenting to a hospital emergency department were recruited along with sex-, age-, and activity-matched, non-concussed, control athletes. Concussion and control participants were assessed six months and one-year following sport-related concussion and study enrolment, respectively. Main outcome measures Participants completed the Post-Concussion Symptom Scale and five condition-specific HRQoL patient-reported outcome measures – Headache Impact Test-6, Fatigue Severity Scale, Neck Disability Index, Generalised Anxiety Disorder-7, and Dizziness Handicap Inventory. We performed Frequentist and Bayesian mixed-design analyses of variance to compare the concussion group and control group at both assessments and quantify whether there was greater evidence in favour of the null hypothesis compared with the alternative hypothesis. Results At six-month and one-year assessments, the concussion group (n = 47; male = 72%; mean (SD) age = 22.68 (5.07)) and the control group (n = 47; male = 72%; mean (SD) age = 23.81 (4.60)) reported similar clinical symptom severity scores and condition-specific HRQoL. The proportion of athletes in the concussion group with clinically-impaired scores was similar to the proportion of non-concussed athletes with clinically-impaired scores. At six-month and one-year assessments, there was moderate-to-very strong evidence that there was no difference between concussion and control participants’ perceptions of the effects of headache, fatigue, neck pain, anxiety, and dizziness on HRQoL. Conclusion There was moderate-to-very strong evidence in favour of no difference between the concussion and control groups on symptom severity scores and condition-specific HRQoL patient-reported outcome measures at six-month and one-year assessments. These results suggest that condition-specific HRQoL returns to the levels of non-concussed individuals within six months following sport-related concussion.

BackgroundArtificial intelligence (AI) is rapidly fueling a fundamental transformation in the practice of pathology. However, AI’s clinical integration remains challenging, with no AI algorithms to date enjoying routine adoption within typical anatomic pathology (AP) laboratories. This survey gathered current expert perspectives and expectations regarding the role of AI in AP from those with first-hand computational pathology and AI experience.MethodsPerspectives were solicited using the Delphi method from 24 subject matter experts between December 2020 and February 2021 regarding the anticipated role of AI in pathology by the year 2030. The study consisted of three consecutive rounds: 1) an open-ended, free response questionnaire generating a list of survey items; 2) a Likert-scale survey scored by experts and analyzed for consensus; and 3) a repeat survey of items not reaching consensus to obtain further expert consensus.FindingsConsensus opinions were reached on 141 of 180 survey items (78.3%). Experts agreed that AI would be routinely and impactfully used within AP laboratory and pathologist clinical workflows by 2030. High consensus was reached on 100 items across nine categories encompassing the impact of AI on (1) pathology key performance indicators (KPIs) and (2) the pathology workforce and specific tasks performed by (3) pathologists and (4) AP lab technicians, as well as (5) specific AI applications and their likelihood of routine use by 2030, (6) AI’s role in integrated diagnostics, (7) pathology tasks likely to be fully automated using AI, and (8) regulatory/legal and (9) ethical aspects of AI integration in pathology.InterpretationThis is the first systematic consensus study detailing the expected short/mid-term impact of AI on pathology practice. These findings provide timely and relevant information regarding future care delivery in pathology and raise key practical, ethical, and legal challenges that must be addressed prior to AI’s successful clinical implementation.FundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.