An introduction to the WHO 5th edition 2022 classification of testicular tumours

The 5th edition of the World Health Organisation Blue Book was published recently and includes a comprehensive update on testicular tumours. This builds upon the work of the 4th edition, retaining its structure and main nomenclature, including the use of the term 'germ cell neoplasia in situ' (GCNIS) for the pre-invasive lesion of most germ cell tumours and division from those not derived from GCNIS. While there have been important developments in understanding the molecular underpinnings of testicular cancer, this updated classification paradigm and approach remains rooted in morphology. Nomenclature changes include replacement of the term 'primitive neuroectodermal tumour' by 'embryonic neuroectodermal tumour' based on the non-specificity of the former term and to separate these tumours clearly from Ewing sarcoma. Seminoma is placed in a germinoma family of tumours emphasising relation to those tumours at other sites. Criteria for the diagnosis of 'teratoma with somatic transformation' have been modified to not include variable field size assessments. The word 'carcinoid' has been changed to 'neuroendocrine tumour', with most examples in the testis now classified as 'prepubertal type testicular neuroendocrine tumour'. For sex cord-stromal tumours, the use of mitotic counts per high-power field has been changed to per mm2 for malignancy assessments, and the new entities, 'signet ring stromal tumour' and 'myoid gonadal stromal tumour', are defined. Well-differentiated papillary mesothelial tumour has now been defined as tumour type with a favourable prognosis. Sertoliform cystadenoma has been removed as an entity from testicular adnexal tumours and placed with Sertoli cell tumours

Acromegaly and Cushing's syndrome caused by a neuroendocrine tumor arising within a sacrococcygeal teratoma.

A 60-year-old man with a pre-existing stable sacrococcygeal teratoma developed acromegaly, ectopic Cushing's syndrome, and 5HIAA secretion. To our knowledge, this represents the first reported case of ACTH and serotonin secretion, and likely GHRH or GH cosecretion, from a sacrococcygeal teratoma in an adult

BAT AGN Spectroscopic Survey-III. An observed link between AGN Eddington ratio and narrow emission line ratios

We investigate the observed relationship between black hole mass ($M_{\rm BH}$), bolometric luminosity ($L_{\rm bol}$), and Eddington ratio (${\lambda}_{\rm Edd}$) with optical emission line ratios ([NII] {\lambda}6583/H{\alpha}, [SII] {\lambda}{\lambda}6716,6731/H{\alpha}, [OI] {\lambda}6300/H{\alpha}, [OIII] {\lambda}5007/H{\beta}, [NeIII] {\lambda}3869/H{\beta}, and HeII {\lambda}4686/H{\beta}) of hard X-ray-selected AGN from the BAT AGN Spectroscopic Survey (BASS). We show that the [NII] {\lambda}6583/H{\alpha} ratio exhibits a significant correlation with ${\lambda}_{\rm Edd}$ ($R_{\rm Pear}$ = -0.44, $p$-value=$3\times10^{-13}$, {\sigma} = 0.28 dex), and the correlation is not solely driven by $M_{\rm BH}$ or $L_{\rm bol}$. The observed correlation between [NII] {\lambda}6583/H{\alpha} ratio and $M_{\rm BH}$ is stronger than the correlation with $L_{\rm bol}$, but both are weaker than the ${\lambda}_{\rm Edd}$ correlation. This implies that the large-scale narrow lines of AGN host galaxies carry information about the accretion state of the AGN central engine. We propose that the [NII] {\lambda}6583/H{\alpha} is a useful indicator of Eddington ratio with 0.6 dex of rms scatter, and that it can be used to measure ${\lambda}_{\rm Edd}$ and thus $M_{\rm BH}$ from the measured $L_{\rm bol}$, even for high redshift obscured AGN. We briefly discuss possible physical mechanisms behind this correlation, such as the mass-metallicity relation, X-ray heating, and radiatively driven outflows.Comment: Accepted for publication in MNRAS, 9 pages, 5 figures, 1 tabl

Validation of a contemporary prostate cancer grading system using prostate cancer death as outcome

BACKGROUND: Gleason scoring (GS) has major deficiencies and a novel system of five grade groups (GS⩽6; 3+4; 4+3; 8; ⩾9) has been recently agreed and included in the WHO 2016 classification. Although verified in radical prostatectomies using PSA relapse for outcome, it has not been validated using prostate cancer death as an outcome in biopsy series. There is debate whether an ‘overall' or ‘worst' GS in biopsies series should be used. METHODS: Nine hundred and eighty-eight prostate cancer biopsy cases were identified between 1990 and 2003, and treated conservatively. Diagnosis and grade was assigned to each core as well as an overall grade. Follow-up for prostate cancer death was until 31 December 2012. A log-rank test assessed univariable differences between the five grade groups based on overall and worst grade seen, and using univariable and multivariable Cox proportional hazards. Regression was used to quantify differences in outcome. RESULTS: Using both ‘worst' and ‘overall' GS yielded highly significant results on univariate and multivariate analysis with overall GS slightly but insignificantly outperforming worst GS. There was a strong correlation with the five grade groups and prostate cancer death. CONCLUSIONS: This is the largest conservatively treated prostate cancer cohort with long-term follow-up and contemporary assessment of grade. It validates the formation of five grade groups and suggests that the ‘worst' grade is a valid prognostic measure

Protein detection using hydrogel-based molecularly imprinted polymers integrated with dual polarisation interferometry

A polyacrylamide-based molecularly imprinted polymer (MIP) was prepared for bovine haemoglobin (BHb). A 3 mg/ml solution of BHb was injected over a dual polarisation interferometer (DPI) sensor to form a physisorbed layer typically of 3.5 ± 0.5 nm thickness. Onto the pre-adsorbed protein layer, MIP and NIP (non-imprinted polymer) were separately injected to monitor the interaction of BHb MIP or NIP particles under different loading conditions with the pre-adsorbed protein layer. In the case of NIP flowing of the protein layer, there was negligible surface stripping of the pre-adsorbed protein. When a protein-eluted sample of MIP particles was flowed over a pre-adsorbed protein layer on the sensor chip, the sensor detected significant decreases in both layer thickness and mass, suggestive that protein was being selectively bound to MIP after being stripped-off from the sensor surface. We also integrated thin-film MIPS for BHb and BSA onto the DPI sensor surface and were able to show that whereas BHb bound selectively and strongly to the BHb MIP thin film (resulting in a sustained increase in thickness and mass), the BHb protein only demonstrated transient and reversible binding on the BSA MIP. MIPs were also tested after biofouling with plasma or serum at various dilutions. We found that serum at 1/100 dilution allowed the MIP to still function selectively. This is the first demonstration of MIPs being integrated with DPI in the development of synthetic receptor-based optical protein sensors. © 2012 Elsevier B.V. All rights reserved

BAT AGN Spectroscopic Survey I: Spectral Measurements, Derived Quantities, and AGN Demographics

We present the first catalog and data release of the Swift-BAT AGN Spectroscopic Survey (BASS). We analyze optical spectra of the majority of AGN (77%, 641/836) detected based on their 14-195 keV emission in the 70-month Swift BAT all-sky catalog. This includes redshift determination, absorption and emission line measurements, and black hole mass and accretion rate estimates for the majority of obscured and un-obscured AGN (74%, 473/641) with 340 measured for the first time. With ~90% of sources at z<0.2, the survey represents a significant census of hard-X-ray selected AGN in the local universe. In this first catalog paper, we describe the spectroscopic observations and datasets, and our initial spectral analysis. The FWHM of the emission lines show broad agreement with the X-ray obscuration (~94%), such that Sy 1-1.8 have NH10^21.9 cm^-2. Seyfert 1.9 show a range of column densities. Compared to narrow line AGN in the SDSS, the X-ray selected AGN have a larger fraction of dusty host galaxies suggesting these types of AGN are missed in optical surveys. Using the most sensitive [OIII]/Hbeta and [NII]/Halpha emission line diagnostic, about half of the sources are classified as Seyferts, ~15% reside in dusty galaxies that lack an Hbeta detection, but for which the line upper limits imply either a Seyfert or LINER, ~15% are in galaxies with weak or no emission lines despite high quality spectra, and a few percent each are LINERS, composite galaxies, HII regions, or in known beamed AGN.Comment: Accepted ApJ, see www.bass-survey.com for dat

Sympathetic activity and early mobilization in patients in intensive and intermediate care with severe brain injuries: a preliminary prospective randomized study.

Patients who experience severe brain injuries are at risk of secondary brain damage, because of delayed vasospasm and edema. Traditionally, many of these patients are kept on prolonged bed rest in order to maintain adequate cerebral blood flow, especially in the case of subarachnoid hemorrhage. On the other hand, prolonged bed rest carries important morbidity. There may be a clinical benefit in early mobilization and our hypothesis is that early gradual mobilization is safe in these patients. The aim of this study was to observe and quantify the changes in sympathetic activity, mainly related to stress, and blood pressure in gradual postural changes by the verticalization robot (Erigo®) and after training by a lower body ergometer (MOTOmed-letto®), after prolonged bed rest of minimum 7 days. Thirty patients with severe neurological injuries were randomized into 3 groups with different protocols of mobilization: Standard, MOTOmed-letto® or Erigo® protocol. We measured plasma catecholamines, metanephrines and blood pressure before, during and after mobilization. Blood pressure does not show any significant difference between the 3 groups. The analysis of the catecholamines suggests a significant increase in catecholamine production during Standard mobilization with physiotherapists and with MOTOmed-letto® and no changes with Erigo®. This preliminary prospective randomized study shows that the mobilization of patients with severe brain injuries by means of Erigo® does not increase the production of catecholamines. It means that Erigo® is a well-tolerated method of mobilization and can be considered a safe system of early mobilization of these patients. Further studies are required to validate our conclusions. The study was registered in the ISRCTN registry with the trial registration number ISRCTN56402432 . Date of registration: 08.03.2016. Retrospectively registered

Prognostic factors for relapse in patients with clinical stage I testicular non-seminoma: A nationwide, population-based cohort study

BACKGROUND: Approximately 30% of patients with clinical stage I non-seminoma (CSI-NS) relapse. Current risk stratification is based on lymphovascular invasion (LVI) alone. The extent to which additional tumor characteristics can improve risk prediction remains unclear.OBJECTIVE: To determine the most important prognostic factors for relapse in CSI-NS patients.DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study including all patients with CSI-NS diagnosed in Denmark between 2013 and 2018 with follow-up until 2022. Patients were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histological slides from the orchiectomy specimens were retrieved.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Histological slides were reviewed blinded to the clinical outcome. Clinical data were obtained from medical records. The association between prespecified potential prognostic factors and relapse was assessed using Cox regression analysis. Model performance was evaluated by discrimination (Harrell's C-index) and calibration.RESULTS: Of 453 patients included, 139 patients (30.6%) relapsed during a median follow-up of 6.3 years. Tumor invasion into the hilar soft tissue of the testicular hilum, tumor size, LVI and embryonal carcinoma were independent predictors of relapse. The estimated 5-year risk of relapse ranged from &lt; 5% to &gt; 85%, depending on the number of risk factors. After internal model validation, the model had an overall concordance statistic of 0.75. Model calibration was excellent.CONCLUSION AND RELEVANCE: The identified prognostic factors provide a much more accurate risk stratification than current clinical practice, potentially aiding clinical decision-making.</p

BAT AGN spectroscopic survey–II. X-ray emission and high-ionization optical emission lines

We investigate the relationship between X-ray and optical line emission in 340 nearby (z ≃ 0.04) AGN selected above 10 keV using Swift BAT. We find a weak correlation between the extinction corrected [O iii] and hard X-ray luminosity (L^(int)_([OIII])∝L_(14-195) with a large scatter (R_(Pear) = 0.64, σ = 0.62 dex) and a similarly large scatter with the intrinsic 2–10 keV to [O iii] luminosities (R_(Pear) = 0.63, σ = 0.63 dex). Correlations of the hard X-ray fluxes with the fluxes of high-ionization narrow lines ([O iii], He ii, [Ne iii] and [Ne v]) are not significantly better than with the low-ionization lines (H α, [S ii]). Factors like obscuration or physical slit size are not found to be a significant part of the large scatter. In contrast, the optical emission lines show much better correlations with each other (σ = 0.3 dex) than with the X-ray flux. The inherent large scatter questions the common usage of narrow emission lines as AGN bolometric luminosity indicators and suggests that other issues such as geometrical differences in the scattering of the ionized gas or long-term AGN variability are important