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

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.

The purpose of this study was to compare the outcomes of open Latarjet (OL) in competitive athletes with primary shoulder instability versus those with recurrent instability versus those undergoing OL for failed prior instability surgery.A retrospective review of patients who underwent OL with a minimum of 24-month follow-up was performed. Additionally, these were pair-matched in a 1:2:1 ratio for age, gender, sport, level of preoperative play, and follow-up length for primary instability, recurrent instability and failed prior instability surgery. Return to sport, the level of return and the timing of return were assessed. Additionally, recurrence, Visual Analogue Scale for pain (VAS), Subjective Shoulder Value (SSV), Rowe score, Shoulder Instability-Return to Sport after Injury (SIRSI) score, satisfaction, and whether they would undergo the same surgery again were compared.After pair-matching, a total of 200 patients were included, with a mean age of 22.7 years and a mean follow-up of 38.8 months. Overall, there was no significant difference in any of the clinical outcome scores (VAS, Rowe, SIRSI, SSV) used for the 3 groups (P0.05 for all). However, there was a significantly lower rate of return to play for those undergoing OL because of failed prior instability surgery (88% vs 91% vs 64%, P0.0001) and for return at the same or a higher level (66% vs 78% vs 56%, P = 0.02). There was no significant difference in the rate of recurrent instability among the 3 groups (6% vs 5% vs 6%, P = 0.95).OL results in excellent clinical outcomes and low recurrence rates for those with primary shoulder instability, those with recurrent instability and those undergoing OL for failed prior instability surgery. However, in those undergoing OL for failed prior stabilization surgery, there was a lower rate of return to play.Level III: Retrospective Comparative Study.

High-grade prostatic adenocarcinoma involving duct/acinar structures is labeled intraductal carcinoma of the prostate (IDCP). As numerous studies have shown that IDCP is associated with high stage disease with a significant negative impact on cancer-specific survival, accurate diagnosis is crucial to ensure appropriate patient management. The definition of IDCP recommended by 2016 World Health Organization (WHO) classification suggests that cases of IDCP with micropapillary or loose cribriform architecture without comedonecrosis should have cells with ≥6× nuclear enlargement. It is unclear how this size criterion was derived and which of the parameters of nuclear size (nuclear diameter, nuclear surface area, or nuclear perimeter) it relates to. To evaluate the extent of nuclear enlargement in IDCP, we performed morphometric analyses relating to each of these parameters in 100 radical prostatectomy specimens. One hundred nuclei from foci of IDCP and 50 nuclei from foci of normal luminal epithelium were examined for each patient. Diagnosis of IDCP was based on cells with definite features of carcinoma present within duct/acinar structures. Comparing the means of each of the parameters between IDCP cells and benign luminal cells, there was a statistically significant enlargement in nuclear perimeter (P

Prostate biopsy data are critical for patient management. Guidelines focus of detailed criteria to ensure that these are precisely and reproducibly reported. However, conflicting recommendations by different expert groups have led to significant reporting variation that could negatively impact patient care. We describe a different approach focusing on optimising communication of histopathological parameters such as tumour extent and grade to the clinical team. Communication is crucial because clinicians usually do not view histological material and are dependent on the information included in the histopathology report. Precision could become less critical if the biopsy findings are effectively conveyed by the pathologist and correctly interpreted by the clinician. Strategies to effectively communicate the message in contentious scenarios such when a prostate needle biopsy set contains prostate cancer that is discontinuous, of borderline grade, of disparate grades or associated with intraductal carcinoma of the prostate are outlined.

Objectives To estimate the times taken to receive clearance to return to sporting activity and to return to pre-injury level of sport competition following sport-related concussion, and to estimate the proportion of athletes who were participating at their pre-injury level of sport competition six months and one-year following sport-related concussion. Design Prospective cohort study. Methods Amateur, adult athletes (16–38 years old) were diagnosed with sport-related concussion at a university-affiliated hospital emergency department. Participants were assessed within one-week, upon medical clearance to return to sporting activity, two weeks following return to sporting activity, six months, and 12 months following sport-related concussion. We assessed sex-, age-, and activity-matched non-injured, control participants at matched time-points. Participants were asked during each study assessment whether they were participating in any sport, in a different sport than before their sport-related concussion, in the same sport but at a lower level of competition than before their sport-related concussion, or in the same sport at the same level of competition than before their sport-related concussion. Results Fifty concussed participants and 50 non-injured, control participants completed the study. The median times taken to receive clearance to return to sporting activity and to return to pre-injury level of sport competition following sport-related concussion were 13 days (95%CI = 12,16) and 31 days (95%CI = 28,32), respectively. One-year following sport-related concussion, 52% of participants reported that they were no longer participating in the same sport and at the same level of competition as they were before their sport-related concussion, compared with only 24% of participants in the non-injured, control group (p = 0.003). Conclusions A greater percentage of athletes in the concussion group were not participating at their perceived pre-injury level of sport competition one-year following sport-related concussion compared with a non-injured control group. Factors that explain the lower proportion of amateur athletes participating at their pre-injury level of sport competition one-year after sport-related concussion are likely multifaceted and should be considered in future investigations.

OBJECTIVES To investigate (i) the presence of vestibular and oculomotor impairments and (ii) the self-perceived effects of concussion-associated dizziness on health-related quality of life among amateur athletes 6 months and 1 year following sport-related concussion compared with nonconcussed, control athletes. DESIGN Prospective, matched-cohort study. SETTING Clinical assessment laboratory. PARTICIPANTS Amateur athletes who were diagnosed with sport-related concussion within 1 week of injury, and sex-, age-, and activity-matched nonconcussed, control athletes. MAIN MEASURES Participants were evaluated 6 months and 1 year following sport-related concussion and enrollment in the longitudinal study using the Vestibular and Oculo-Motor Screening and the Dizziness Handicap Inventory. We performed multivariate analyses of variance and chi-square analyses to compare concussion and control group scores at each study assessment. RESULTS Forty-seven participants with concussion and 47 control participants completed the study. The concussion group reported similar mean symptom provocation scores on the Vestibular and Oculo-Motor Screening and exhibited a similar near-point convergence distance compared with the control group at the 6-month and 1-year study assessments. The concussion and control groups had similar perceptions of the effects of dizziness on their health-related quality of life at both study assessments. CONCLUSION Meaningful differences in vestibular and oculomotor symptom provocation and self-perceived effects of dizziness on everyday life were not observed between concussed and nonconcussed, control athletes 6 months and 1 year following sport-related concussion.

Background Manual microscopy remains a widely-used tool for malaria diagnosis and clinical studies, but it has inconsistent quality in the field due to variability in training and field practices. Automated diagnostic systems based on machine learning hold promise to improve quality and reproducibility of field microscopy. The World Health Organization (WHO) has designed a 55-slide set (WHO 55) for their External Competence Assessment of Malaria Microscopists (ECAMM) programme, which can also serve as a valuable benchmark for automated systems. The performance of a fully-automated malaria diagnostic system, EasyScan GO, on a WHO 55 slide set was evaluated. Methods The WHO 55 slide set is designed to evaluate microscopist competence in three areas of malaria diagnosis using Giemsa-stained blood films, focused on crucial field needs: malaria parasite detection, malaria parasite species identification (ID), and malaria parasite quantitation. The EasyScan GO is a fully-automated system that combines scanning of Giemsa-stained blood films with assessment algorithms to deliver malaria diagnoses. This system was tested on a WHO 55 slide set. Results The EasyScan GO achieved 94.3 % detection accuracy, 82.9 % species ID accuracy, and 50 % quantitation accuracy, corresponding to WHO microscopy competence Levels 1, 2, and 1, respectively. This is, to our knowledge, the best performance of a fully-automated system on a WHO 55 set. Conclusions EasyScan GO’s expert ratings in detection and quantitation on the WHO 55 slide set point towards its potential value in drug efficacy use-cases, as well as in some case management situations with less stringent species ID needs. Improved runtime may enable use in general case management settings.

Grading is one of the best prognostic indicators of prostate cancer with Gleason grade 5 having the worst outcome. The prognostic influence of grade 5 patterns remains uncertain. A total of 646 prostate needle biopsy sets with Gleason score (GS) 9-10 prostatic adenocarcinoma were prospectively analysed. Patterns of grade 5 were correlated with radical prostatectomy (RP) adverse findings of high tumour volume (TV), extra-prostatic extension (EPE), seminal vesicle invasion (SVI) and lymph node involvement (LNI) in 472 and biochemical recurrence (BCR) in 338 patients after RP. Mean age and serum PSA were 69 years (range 37-91) and 26.1 ng/mL (range 1.4-1800), respectively. Gleason scores were 4+5=9 in 539 (83%), 5+4=9 in 94 (15%) and 5+5=10 in 13 cases (2%). Clusters/cords, single cells, sheets and comedocarcinoma were found in 86%, 69%, 26% and 18% with a pure pattern in 25% of cases. Comparing cases with and without sheets, there were no significant differences with RP high TV (p=0.8577), EPE (p=0.5372), SVI (p=0.5183) and LNI (p=0.4323). However, the presence of sheets predicted a significantly higher BCR rate (p=0.0033), while for tumours with single cells, the interval to BCR was significantly shorter (p0.0001). Comparing cases with and without the other patterns, two other significant differences were found. Comedocarcinoma predicted high TV (p=0.0230) and single cells predicted EPE (p=0.0101). This study shows that all patterns currently used to assign a Gleason grade 5, including sheets, comedocarcinoma, single cells and clusters/cords, are associated with aggressive outcomes validating their inclusion in grade 5.

BACKGROUND AND PURPOSE: Hip fracture guidelines emphasize mobilization within 48 hours of surgery. The aims of this audit were to determine the proportion of patients with hip fracture who mobilize within 48 hours, identify factors associated with delayed mobilization, and identify barriers to mobilization. METHODS: Single-site prospective audit of 100 consecutive patients (age 82 ± 9 years) admitted for surgical management of hip fracture. Data collected included time to mobilization, factors that may impact mobilization (age, weight-bearing status, additional injuries, premorbid mobility status, time to surgery, dementia, delirium, and postoperative complications), and barriers to mobilization as identified by the physical therapist. RESULTS AND DISCUSSION: Mobilization within 48 hours of surgery was achieved by 43% of patients. Multivariate logistic regression demonstrated odds of mobilizing early increased with higher New Mobility Scores, representing better premorbid mobility (odds ratio [OR] = 1.30; 95% confidence interval [CI], 1.06-1.60); odds reduced if delirium was present on day 1 or 2 (OR = 0.25; 95% CI, 0.08-0.79). New Mobility Scores 5 or more, which indicate independent premorbid mobility inside and outside the house, best predicted early mobilization in patients who did not develop delirium. No cutoff score was identified for those with delirium. Identified barriers to mobilization included patient confusion, manual handling risk, patient declined, and hypotension. CONCLUSIONS: Less than half of this cohort achieved the guideline of mobilization within 48 hours of surgery. Patients who develop delirium within the first 2 days of surgery or who had premorbid mobility limitation were less likely to mobilize. Identification of patients likely to have delayed mobilization will assist physical therapists with delivering appropriate management to patients with hip fracture during their acute hospital stay.

The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance and many do not need to be reported. Their clinical relevance lies in the risk that they are misinterpreted as cancer. This review presents the histopathological features of benign mimics and discusses their distinction from cancer. The lesions that are most often misdiagnosed as cancer are atrophy and its variants, including simple atrophy, partial atrophy and post-atrophic hyperplasia. Benign proliferations are a group of lesions with crowded small glands with no or little nuclear atypia. The most problematic entity of this group is adenosis, which may have a more alarming architecture than some cancers. A diagnostic problem with atrophy and several of the benign proliferations is that the glands often have a discontinuous or absent basal cell layer. Hyperplastic and metaplastic lesions include basal cell hyperplasia. Basal cell hyperplasia may especially mimic prostate cancer with its small dark glands, variable nuclear atypia and a pseudoinfiltrative pattern, which may be present. The anatomical structure that most often causes diagnostic problems is the seminal vesicle. The mucosa of the seminal vesicle contains small acini, often with very pronounced nuclear atypia that may be misinterpreted as cancer. Pathologists need to be familiar with these mimics, as a false positive diagnosis of prostate cancer may lead to unnecessary radical treatment.

There are a number of benign epithelial proliferations in the bladder that may be difficult to distinguish from carcinomas, including urothelial carcinoma and its variants, squamous cell carcinoma and adenocarcinoma. If misdiagnosed, there is the potential for over treatment, with its attendant risk of complications, as well as errors relating to prognostic assessment. In the case of the misdiagnosis of high grade proliferative lesions that mimic invasive carcinoma, unnecessary radical surgery, chemotherapy and radiotherapy may result. Similarly, the misdiagnosis of lesions that have the appearance of low grade carcinoma can prompt a lifetime of radiological investigation and cystoscopies. In this review, we discuss a variety of entities that may be diagnostically challenging and emphasise the importance of identifying key morphological features that have diagnostic utility. We also highlight the importance of relevant clinical information and the clinical settings in which these lesions may occur. In this review we have divided the lesions on the basis of morphology in order to facilitate discussion relating to the differential diagnosis. The architectural patterns we discuss include papillary lesions (polypoid/papillary cystitis and papillary urothelial hyperplasia), pseudocarcinomatous proliferations (pseudocarcinomatous urothelial hyperplasia, florid proliferation of von Brunn nests and fibroepithelial polyps), glandular lesions (intestinal metaplasia and müllerianosis) and lesions with several different patterns (prostatic type urethral polyps and nephrogenic adenoma or metaplasia).

Most studies report injuries based upon their incidence rate, or the number of injuries which occur in a sport per unit of time. While this is recommended across numerous consensus statements on reporting injury data in sport, it may be of benefit to consider injury burden also. Reporting injuries as the duration of injury per 1000 exposure hours highlights those injuries which will likely cause greater disruption within a team. Therefore, the primary aim of this study was to report the burden of injury in field hockey. This secondary analysis of epidemiological data employed two methods of data collection: self-reported through an online reporting software, and through contact with the team physiotherapist. Athletes reported injury-related symptoms for 4170 days in total, giving rise to an injury burden of 121.0/1000 h, of which 61.4/1000 h were days lost through injury. Injuries to the hamstring, as well as muscle strain injuries, caused the most significant injury burden in athletes (22.6 and 35.8/1000 h respectively). Reporting injuries as the duration of injuries per 1000 hours highlights those injuries which cause the most significant disruption within a squad. Future injury prevention strategies in field hockey should prioritize the injuries which are most burdensome.

To prospectively investigate the recovery of athlete-reported symptoms and the condition-specific health-related quality of life (HRQoL) following sport-related concussion.Prospective matched-cohort study.We recruited amateur athletes who were diagnosed with sport-related concussion by emergency department physicians. Study participants were assessed at 3 time points following sport-related concussion. At each assessment, participants completed 5 condition-specific HRQoL patient-reported outcome measures to evaluate participants' perceptions of the effects of specific concussion-related symptoms on their HRQoL. We performed log-linear analyses to assess the proportion of concussed participants with clinically impaired condition-specific HRQoL compared with the proportion of participants in the control group with clinically impaired condition-specific HRQoL.Fifty participants with sport-related concussion and 50 control participants matched by sex, age, and activity completed the study. Upon return to sporting activity, there was a significantly greater proportion of participants in the concussion group who perceived that headache, neck pain, and dizziness had an adverse effect on their HRQoL compared with the control group. Two weeks after return to sporting activity, there was still a significantly greater proportion of participants in the concussion group who perceived that headache (Of concussed participants, 1 in 4 perceived that headache and dizziness had adverse effects on their HRQoL after returning to sporting activity following sport-related concussion compared with nonconcussed, control participants.

The International Collaboration on Cancer Reporting (ICCR) has developed a suite of detailed datasets for international implementation. These datasets are based on the reporting protocols developed by the Royal College of Pathologists (UK), The Royal College of Pathologists of Australasia and the College of American Pathologists, with modifications undertaken by international expert groups appointed according to ICCR protocols. The dataset for the reporting of renal biopsy for tumour is designed to provide a structured reporting template containing minimum data recording key elements suitable for international use. In formulating the dataset, the ICCR panel incorporated recommendations from the 2012 Vancouver Consensus Conference of the International Society of Urological Pathology (ISUP) and the 2016 edition of the WHO Bluebook on tumours of the urinary and male genital systems. Reporting elements were divided intoRequired(Core) andRecommended(Non-core) components of the report.Requiredelements are as follows: specimen laterality, histological tumour type, WHO/ISUP histological tumour grade, sarcomatoid morphology, rhabdoid morphology, necrosis, lymphovascular invasion and coexisting pathology in non-neoplastic kidney.Recommendedreporting elements are as follows: operative procedure, tumour site(s), histological tumour subtype and details of ancillary studies. In particular, it is noted that fluorescence in situ hybridisation studies may assist in diagnosing translocation renal cell carcinoma (RCC) and in distinguishing oncocytoma and eosinophilic chromophobe RCC. It is anticipated that the implementation of this dataset into routine clinical practice will facilitate uniformity of pathology reporting worldwide. This, in turn, should have a positive impact on patient treatment and the quality of demographic information held by cancer registries.

Age-related impairments in motor performance are caused by a deterioration in mechanical and neuromuscular functions, which have been investigated from the macro-level of muscle-tendon unit to the micro-level of the single muscle fiber. When compared to the healthy young skeletal muscle, aged skeletal muscle is: (1) weaker, slower and less powerful during the performance of voluntary contractions; (2) less steady during the performance of isometric contractions, particularly at low levels of force; and (3) less susceptible to fatigue during the performance of sustained isometric contractions, but more susceptible to fatigue during the performance of high-velocity dynamic contractions. These impairments have been discussed to be mainly the result of: a) loss of muscle mass and selective atrophy of type II muscle fibers; b) altered tendon mechanical properties (decreased tendon stiffness); c) reduced number and altered function of motor units; d) slower muscle fiber shortening velocity; e) increased oscillation in common synaptic input to motor neurons; and f) altered properties and activity of sarcoplasmic reticulum. In this second part of a two-part review we have detailed the age-related impairments in motor performance with a reference to the most important mechanical and neuromuscular contributing factors.

Background Prostate multiparametric magnetic resonance imaging (mpMRI) has become a popular initial investigation of an elevated PSA and is being incorporated into active surveillance protocols. Decisions on prostate cancer investigation and management based solely on a normal mpMRI remains controversial. Histopathological findings of a totally embedded normal mpMRI lobe are rarely described. Methods A retrospective review of the histological findings of negative preoperative mpMRI lobes in men treated by robot assisted laparoscopic radical prostatectomy (RALP). Inclusion criteria included a preoperative low risk mpMRI for both lobes (Prostate Imaging-Reporting and Data System (PIRADS) ≤ 2) or one negative lobe (with a PIRADS 3-5 in the opposite lobe). Results A single normal mpMRI lobe was identified in 1018 men (PIRADS 3-5 group). Both lobes were normal in 179 men (PIRADS ≤ 2 group). Prostate cancer was identified in 47.6% (485/1018) of the normal mpMRI lobe opposite a PIRADS 3-5 lesion, including 13.2% (134/1018) with >0.5 cc of International Society of Urologic Pathologists (ISUP) grade 2, or a higher grade cancer. ISUP grade 4-5 was only identified in 2% (20/1018). Compared to RALP histology of the PIRADS 3-5 mpMRI tumour, a pathological ISUP upgrade in the normal mpMRI lobe was identified in 58/1018 men (5.7%). In the PIRADS ≤ 2 group extraprostatic extension occurred in 19% (34/179) and seminal vesicle invasion (pT3b) in 3.9% (7/179). There was no difference in margin status between the PIRADS 3-5 and ≤2 groups (p = 0.247). Conclusions mpMRI underestimates tumour grade and volume compared to totally embedded histopathological analysis of RALP specimens, although ISUP grade 4-5 cancer is uncommon. Our analysis provides useful insight into the multifocality of prostate cancers, and highlights the utility of systematic biopsy, in addition to targeted biopsies. These results have ramifications for clinical decisions on prostate cancer management based solely on the mpMRI appearance, including active surveillance.

Objective To evaluate the ability of preoperative multiparametric magnetic resonance imaging (mpMRI) and a gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (Ga-68-PSMA PET/CT) scan to predict pathological outcomes and also identify a group of men with a 30% risk of microscopic LNM despite a negative preoperative(68)Ga-PSMA PET/CT and this high-risk group would appear suitable for an extended PLND at the time of a radical prostatectomy.

Transmembrane serine protease 2 is encoded by the TMPRSS2 gene. The gene is widely conserved and has two isoforms, both being autocatalytically activated from the inactive zymogen form. A fusion gene between the TMPRSS2 gene and ERG (erythroblast-specific-related gene), an oncogenic transcription factor, is the most common chromosomal aberration detected in prostate cancer, responsible for driving carcinogenesis. The other key role of TMPRSS2 is in priming the viral spike protein which facilitates viral entry essential for viral infectivity. The protease activates a diverse range of viruses. Both SARS-CoV and SARS-CoV-2 (COVID-19) use angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 to facilitate entry to cells, but with SARS-CoV-2 human-to-human transmission is much higher than SARS-CoV. As TMPRSS2 is expressed outside of the lung, and can therefore contribute to extrapulmonary spread of viruses, it warrants further exploration as a potential target for limiting viral spread and infectivity.

Foci of necrosis are frequently seen in malignant tumours and may be due to a variety of causes. Different types of necrosis are given various names based upon their morphological features and presumed pathogenesis, such as coagulative, liquefactive and fibrinoid necrosis. Here, we propose the term 'granular necrosis' (GN) for a specific form of tumour necrosis characterised by the presence of well-defined necrotic foci being sharply demarcated from adjacent viable tumour. A constant feature is loss of architecture resulting in an amorphous necrotic mass containing granular nuclear and cytoplasmic debris, without an associated neutrophilic infiltrate. There is usually extensive karyorrhexis, which in larger tumours is more prominent at the periphery. These foci are often microscopic but may range up to several millimetres or larger in size. This distinctive form of necrosis has been erroneously given a variety of names in the literature including coagulative necrosis and microscopic necrosis, which on the basis of the aforementioned gross and microscopic findings is inappropriate. It is apparent that this is a specific form of necrosis, hence the descriptive term 'granular necrosis' that differentiates this form of necrosis from other types. The presence of GN is recognised as occurring in a variety of tumour types, being commonly seen in renal cell carcinoma, where it has been shown to have independent prognostic significance. In some epithelial and stromal tumours of the uterus, the presence of GN also has prognostic significance and is a defining feature for the differentiation of uterine leiomyoma and leiomyosarcoma. The pathogenesis of GN is unresolved. It does not show the features of apoptosis and in recent studies has been shown to have some of the molecular changes associated with necroptosis.

Determining the rate and severity of injuries incurred through sport is accepted as the primary step towards designing, implementing and evaluating injury prevention programmes. The aim of this study was to determine the injury incidence rate and characteristics of male field hockey athletes participating in the Irish Hockey League. Athletes from eight field hockey teams were assigned to an online reporting system, where they logged injuries as they were incurred. Injuries were defined as any physical complaint. Coaches and physiotherapists were contacted weekly to corroborateinjuries. Overall 323 injuries were reported across 34,449 exposure hours, giving rise to an incidence rate of 9.4/1000 h. On average, athletes sustained one injury over the course of two seasons. Muscle strains, pain and contusions were the most common types of injury, while the hamstring, knee and hip/groin were the most frequently reported locations. While 66.9% of injuries occurred through non-contact mechanisms, contact injuries were also common. Injury recurrences accounted for 16.1% of injuries. In conclusion, the incidence of injury in field hockey is high, occurring from a variety of mechanisms. Future injury prevention strategies should prioritise injuries to the hamstring, knee and ankle, and be specific to particular playing positions.

A challenge in the diagnosis of prostate pathology is the numerous benign mimics of prostatic adenocarcinoma. Most of these lesions have no clinical significance but may be misinterpreted as cancer in biopsy specimens. In this review we describe the features of some of the more common benign mimics and discuss how they can be distinguished from carcinoma. The diagnostic entities most commonly associated with a false positive diagnosis of cancer are the atrophic group of lesions that include simple atrophy, partial atrophy and post-atrophic hyperplasia. Benign proliferations exhibit architectural atypia, often with closely packed small glands, but with no or little nuclear atypia. The most common diagnostic pitfall of this group is adenosis, which may have an even more atypical architecture than some cancers. A common denominator of atrophy and benign proliferations is that they consist of small glands that may have a patchy or absent basal cell layer, which adds to the diagnostic difficulties. Amongst hyperplastic and metaplastic lesions, basal cell hyperplasia may be misinterpreted as cancer because of its dark basophilic glands that sometimes display a certain degree of nuclear atypia and occasionally exhibit a pseudoinfiltrative pattern. The most important extraprostatic anatomical structure causing diagnostic difficulties is the seminal vesicle. The closely clustered small glands and often strikingly atypical nuclei of seminal vesicle epithelium may be misinterpreted as cancer. Awareness of these mimics is of paramount importance for the practicing pathologist as a false positive diagnosis of prostate cancer may lead to unnecessary radical therapy.

Aims Perineural invasion (PNI) by prostatic adenocarcinoma is debated as a prognostic parameter. This study investigates the prognostic predictive value of PNI in a series of patients with locally advanced prostate cancer treated with radiotherapy and androgen deprivation using 10 years outcome data from the TROG 03.04 RADAR trial. Methods Diagnostic prostate biopsies from 976 patients were reviewed and the presence of PNI noted. Patients were followed for 10 years according to the trial protocol or until death. The primary endpoint for the study was time to bone metastasis. Secondary endpoints included time to soft tissue metastasis, transition to castration resistance, prostate cancer-specific mortality and all-cause mortality. Results PNI was detected in 449 cases (46%), with 234 cases (24%) having PNI in more than one core. The presence of PNI was significantly associated with higher ISUP grade, clinical T staging category, National Comprehensive Cancer Network risk group, and percent positive biopsy cores. The cumulative probability of bone metastases according to PNI status was significant over the 10 years follow-up interval of the study (log-rank testP < 0.0001). PNI was associated with all endpoints on univariable analysis. After adjusting for baseline clinicopathological and treatment factors, bone metastasis was the only endpoint in which PNI retained its prognostic significance (hazard ratio 1.42, 95% confidence interval 1.05-1.92,P = 0.021). Conclusions The association between PNI and the development of bone metastases supports the inclusion of this parameter as a component of the routine histology report. Further this association suggests that evaluation of PNI may assist in selecting those patients who should be monitored more closely during follow-up.

Rarely, salivary gland tumors such as mucoepidermoid carcinoma, mammary analogue secretory carcinoma and mucinous carcinoma arise as primary tumors from ectopic or metaplastic salivary gland tissue adjacent to or within the thyroid gland. We report for the first time a case of primary salivary acinic cell carcinoma (AcCC) adjacent to the thyroid gland in a 71-year-old female patient with Crohns disease and a previous history of malignant melanoma. Following the development of a nodule adjacent to the left thyroid lobe, a fine-needle aspiration biopsy was reported as consistent with a follicular lesion of undetermined significance (Bethesda III). A left-sided hemithyroidectomy was performed. A circumscribed lesion measuring 33 mm was noted adjacent to the thyroid and trapping parathyroid, it was composed of solid nests and glands with microcystic and follicular patterns. The tumor was negative for thyroid, parathyroid and paraganglioma markers, but positive for pan-cytokeratins, CK7, CD10, CD117, androgen receptor and HNF-beta. A metastasis of a thyroid-like renal cell carcinoma was suspected but ruled out, and the patient had no evident lesions on extensive radiology of the urogenital, pulmonary and GI tracts. Based on the morphology, a diagnosis of AcCC was suggested, and confirmed with DOG1 and PAS-diastase staining. Molecular analyses pinpointed a constitutional ASXL1 variant of uncertain significance, but no fusion events. The patient had no radiological or clinical evidence of parotid, submandibular or sublingual tumors postoperatively, and the excised lesion was therefore assumed to be a primary tumor. We here detail the morphological and immunophenotypic profile of this previously undescribed perithyroidal tumor.

Context:Decreased postural balance is a primary risk factor for lower-limb injuries. Cryotherapy is commonly utilized by clinicians to provide local analgesia for minor acute knee joint musculoskeletal injuries during breaks in play or at halftime. Its effect on dynamic postural balance remains unclear.Objective:To investigate the acute effects of a 15-minute knee joint cryotherapy application on dynamic postural balance, as assessed primarily via a clinically oriented outcome measure.Design:Experimental study.Setting:University biomechanics laboratory.Patients or Participants:A total of 28 elite-level college male field-sport athletes.Intervention:Participants were tested on the anterior, posteromedial, and posterolateral reach directions of the Star Excursion Balance Test both before and after a 15-minute knee joint cryotherapy application.Main Outcome Measure(s):Normalized reach distances, 3-dimensional knee joint kinematics, sagittal plane hip and ankle joint kinematics, as well as fractal dimension of the center-of-pressure path during the performance of the anterior, posteromedial, and posterolateral reach directions of the Star Excursion Balance Test.Results:There was a statistically significant decrease in reach distance scores achieved on anterior, posteromedial, and posterolateral directions of the Star Excursion Balance Test from precryotherapy to postcryotherapy (P P > .05). No significant change in fractal dimension was observed for any reach direction following cryotherapy application (P > .05).Conclusions:The results of the present study indicate that dynamic postural balance is unlikely to be adversely affected immediately following cryotherapy application to the knee joint.

The International Collaboration on Cancer Reporting (ICCR) is an alliance of major pathology organisations in Australasia, Canada, Europe, United Kingdom, and United States of America that develops internationally standardised, evidence-based datasets for the pathology reporting of cancer specimens. This dataset was developed by a multidisciplinary panel of international experts based on previously published ICCR guidelines for the production of cancer datasets. It is composed of Required (core) and Recommended (noncore) elements identified on the basis of literature review and expert consensus. The document also includes an explanatory commentary explaining the rationale behind the categorization of individual data items and provides guidance on how these should be collected and reported. The dataset includes nine required and six recommended elements for the reporting of cancers of the urinary tract in biopsy and transurethral resection (TUR) specimens. The required elements include specimen site, operative procedure, histological tumor type, subtype/variant of urothelial carcinoma, tumor grade, extent of invasion, status of muscularis propria, noninvasive carcinoma, and lymphovascular invasion (LVI). The recommended elements include clinical information, block identification key, extent of T1 disease, associated epithelial lesions, coexistent pathology, and ancillary studies. The dataset provides a structured template for globally harmonized collection of pathology data required for management of patients diagnosed with cancer of the urinary tract in biopsy and TUR specimens. It is expected that this will facilitate international collaboration, reduce duplication of effort in updating current national/institutional datasets, and be particularly useful for countries that have not developed their own datasets.

To clarify the relative effects of duration of androgen suppression (AS) and radiation dose escalation (RDE) on distant progression (DP) in men with locally advanced prostate cancer.Participants with locally advanced prostate cancer in the TROG 03.04 RADAR trial were randomized to 6 or 18 months AS ± 18 months zoledronic acid (Z). The trial incorporated a RDE program by stratification at randomization and dosing options were 66, 70, or 74 Gy external beam radiation therapy (EBRT), or 46 Gy EBRT plus high-dose-rate brachytherapy boost (HDRB). The primary endpoint for this study was distant progression (DP). Secondary endpoints included local progression, bone progression, prostate cancer-specific mortality and all-cause mortality. Effect estimates for AS duration and RDE were derived using Fine and Gray competing risk models adjusting for use of Z, age, tumor stage, Gleason grade group, prostate-specific antigen, and treatment center. Cumulative incidence at 10 years was estimated for each RDE group.A total of 1051 out of 1071 randomized subjects were eligible for inclusion in this analysis. Compared with 6 months AS, 18 months AS significantly reduced DP independently of radiation dose (subhazard ratio 0.70; 95% confidence interval [CI], 0.56-0.87; P = .002). No statistically significant interaction between effect of AS duration and RT dose was observed (Wald test P = .76). In subgroup analyses, DP was significantly reduced by the longer duration of AS in the 70 Gy and HDRB groups but not in the 66 Gy and 74 Gy. Compared with 70 Gy, HDRB significantly reduced DP (subhazard ratio 0.68 [95% CI, 0.57-0.80]; P.0001) independently of AS duration. At 10 years, adjusted cumulative incidences were 26.1% (95% CI, 18.9%-33.2%), 26.7% (22.9%-30.6%), 24.9% (20.0%-29.8%) and 19.7% (15.5%-23.8%) for DPs in the respective radiation dose groups.Compared with 6 months AS, 18 months AS reduced DP independently of radiation dose. Men treated with HDRB gained a significant benefit from a longer duration of AS. Evidence of improved oncologic outcomes for HDRB compared with dose-escalated EBRT needs to be confirmed in a randomized trial.

We investigated the pattern of injuries in elite-level womens football in Ireland, during a two-season prospective injury surveillance study in the Womens National League (WNL). Seven out of the eight clubs (271 players) in the WNL were followed prospectively during the 2018 and 2019 seasons. The injury incidence rate in matches (19.2/1000 h) was 7.5 times higher than in training (2.5/1000 h). Players, on average, sustained 0.69 injuries per season (266 injuries/383 player seasons), which equates to 15 time-loss injuries per season for a squad of 22 players. The majority of the injuries sustained by players were lower extremity injuries (85%), of which, 46% had a non-contact injury mechanism. Muscle, ligament, and contusion injuries were the most common injury types, while the ankle, knee, and thigh were the most commonly injured body sites. The most common injuries sustained over the two seasons were lateral ankle sprains (13.9%), hamstring strains (12.4%), knee meniscus/cartilage injuries (7.5%), adductor strains (6%), quadriceps strains (4.5%), and ankle contusions (4.5%). The injuries with the highest injury burden were ACL injuries (59 days lost/1000 h), knee meniscus/cartilage injuries (23/1000 h), lateral ankle sprains (21/1000 h), hamstring strains (12/1000 h), MCL sprains (11/1000 h), and quadriceps strains (11/1000 h). There were 8 ACL tears documented over the 2 seasons, which accounted for 28% of all time lost to injury with a mean days lost per injury of 247. We recommend that clubs in the WNL in Ireland should implement injury risk mitigation strategies, with a particular focus on injuries with a high injury burden. Funding Agencies|Irish Research Council Enterprise Partnership Scheme (Postgraduate) awardIrish Research Council for Science, Engineering and Technology

Poor reporting of medical and healthcare systematic reviews is a problem from which the sports and exercise medicine, musculoskeletal rehabilitation, and sports science fields are not immune. Transparent, accurate and comprehensive systematic review reporting helps researchers replicate methods, readers understand what was done and why, and clinicians and policy-makers implement results in practice. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and its accompanying Explanation and Elaboration document provide general reporting examples for systematic reviews of healthcare interventions. However, implementation guidance for sport and exercise medicine, musculoskeletal rehabilitation, and sports science does not exist. The Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science (PERSiST) guidance attempts to address this problem. Nineteen content experts collaborated with three methods experts to identify examples of exemplary reporting in systematic reviews in sport and exercise medicine (including physical activity), musculoskeletal rehabilitation (including physiotherapy), and sports science, for each of the PRISMA 2020 Statement items. PERSiST aims to help: (1) systematic reviewers improve the transparency and reporting of systematic reviews and (2) journal editors and peer reviewers make informed decisions about systematic review reporting quality.

Prostate cancer is the second most common cancer in men worldwide. Despite an abundance of prostate-specific antigens, immunotherapies have yet to become a standard of care, potentially limited by T-cell dysfunction. Up to 10% of human circulating T-cells, and a significant fraction in the urogenital tract, are mucosal-associated invariant T (MAIT) cells. MAIT cells express stereotyped T-cell receptors that recognize riboflavin metabolites derived from microbes presented by MR-1. We evaluated the number, phenotype and function of circulating MAIT cells, alongside two other innate-like T (ILT) -cell subsets, in men with prostate cancer and age- and sex-matched controls. MAIT cells in men with prostate cancer circulated at similar frequencies to controls, but their cytokine production and proliferation was impaired. In contrast, the function of two other ILT-cell populations (natural killer T-cells and Vγ9Vδ2 T-cells) was not impaired. In both patients and controls, MAIT cells expressed high levels of the immune checkpoint molecule PD-1 at rest, while upregulation of PD-1 in response to the MR-1 ligand 5-amino-6D-ribitylaminouracil (5-A-RU) was greater in patients. 5-A-RU also induced upregulation of PD-L1 and -L2 RNA in primary mononuclear cells. We confirmed that circulating MAIT cell number and function were preserved before and during anti-PD1 therapy with pembrolizumab in a cohort of patients with melanoma. In vitro, 5-A-RU enhanced mononuclear cell cytotoxicity against the PD-L1 positive prostate cancer cell line PC3 in an MR-1-dependent manner. Addition of pembrolizumab enhanced this cytotoxicity, and was associated with increased MAIT cell expression of CD107a and IFN-γ. We conclude that prostate cancer is associated with MAIT-cell dysfunction, and that this might be overcome through the application of potent MR-1 ligands with PD-1 blockade. These findings may have implications for the development of cancer immunotherapies that exploit MAIT cells.

We have read with interest the recent debate between Drs Varma and Epstein regarding the grading of intraductal carcinoma of the prostate.$^{1}$ Unfortunately, the arguments as presented do little to abate the confusion surrounding this so-called diagnostic entity.

The presence of a cribriform pattern is now recognized as a clinically important, independent adverse prognostic indicator for prostate cancer. For this reason the International Society of Urological Pathology (ISUP) recently recommended its inclusion in standard reporting. In order to improve interobserver agreement as to the diagnosis of cribriform patterns, the ISUP assembled an international panel of 12 expert urogenital pathologists for the purpose of drafting a consensus definition of cribriform pattern in prostate cancer, and provide their opinions on a set of 32 images and on potential diagnostic criteria. These images were selected by the 2 nonvoting convenors of the study and included the main categories where disagreement was anticipated. The Delphi method was applied to promote consensus among the 12 panelists in their review of the images during 2 initial rounds of the study. Following a virtual meeting, convened to discuss selected images and diagnostic criteria, the following definition for cribriform pattern in prostate cancer was approved: "A confluent sheet of contiguous malignant epithelial cells with multiple glandular lumina that are easily visible at low power (objective magnification ×10). There should be no intervening stroma or mucin separating individual or fused glandular structures"together with a set of explanatory notes. We believe this consensus definition to be practical and that it will facilitate reproducible recognition and reporting of this clinically important pattern commonly seen in prostate cancer. The images and the results of the final Delphi round are available at the ISUP website as an educational slide set (https://isupweb.org/isup/blog/slideshow/cribriform-slide-deck/).

Inadequate sleep and poor eating behaviours are associated with higher risk of childhood overweight and obesity. Less is known about the influence sleep has on eating behaviours and consequently body composition. Furthermore, whether associations differ in boys and girls has not been investigated extensively. We investigate associations between sleep, eating behaviours and body composition in cross-sectional analysis of 5-year-old children. Weight, height, BMI, mid upper arm circumference (MUAC), abdominal circumference (AC) and skinfold measurements were obtained. Maternal reported information on child’s eating behaviour and sleep habits were collected using validated questionnaires. Multiple linear regression examined associations between sleep, eating behaviours and body composition. Sleep duration was negatively associated with BMI, with 1-h greater sleep duration associated with 0·24 kg/m2 (B = 0·24, CI −0·42, −0·03, P = 0·026) lower BMI and 0·21 cm lower (B = –0·21, CI −0·41, −0·02, P = 0·035) MUAC. When stratified by sex, girls showed stronger inverse associations between sleep duration (h) and BMI (kg/m2) (B = –0·32; CI −0·60, −0·04, P = 0·024), MUAC (cm) (B = –0·29; CI −0·58, 0·000, P = 0·05) and AC (cm) (B = –1·10; CI −1·85, −0·21, P = 0·014) than boys. Positive associations for ‘Enjoys Food’ and ‘Food Responsiveness’ with BMI, MUAC and AC were observed in girls only. Inverse associations between sleep duration and ‘Emotional Undereating’ and ‘Food Fussiness’ were observed in both sexes, although stronger in boys. Sleep duration did not mediate the relationship between eating behaviours and BMI. Further exploration is required to understand how sleep impacts eating behaviours and consequently body composition and how sex influences this relationship.

Hamstring strains are the most prevalent injury sustained by field-sport athletes. Insufficiencies in the architectural characteristics of the hamstring muscles can heighten an athlete’s risk of incurring a hamstring strain. To evaluate the influence of hamstring muscle architectural characteristics (i. e., fascicle length, pennation angle, muscle thickness) on injury risk, it is necessary to precisely evaluate these characteristics. Considering this, our aim was to develop and evaluate the precision of a novel semi-automated tracing software to measure the architectural characteristics of the biceps femoris long head (the most commonly injured hamstring muscle) in B-mode ultrasound images. We acquired static sonograms of the biceps femoris long head from ten healthy male field-sport athletes. The architectural characteristics (fascicle length, pennation angle, and muscle thickness) of participants’ biceps femoris long head were evaluated 10 times using the tracing software, with the specific purpose of determining its measurement precision. The tracing software precisely measured the architectural characteristics of the participants’ biceps femoris long head: fascicle length (% CV: 0.64–1.12), pennation angle (% CV: 2.58–10.70), muscle thickness (% CV: 0.48–2.04) Our semi-automated skeletal muscle tracing algorithm precisely measures fascicle length, pennation angles, and muscle thickness of the biceps femoris long head in static B-mode ultrasound images.

Among four sub-patterns of Gleason grade 4 prostate cancer, voluminous evidence supports that the cribriform pattern holds an unfavorable prognostic impact, as compared with poorly-formed, fused, or glomeruloid. The International Society of Urological Pathology (ISUP) recommends specifying whether invasive grade 4 cancer is cribriform. Recently, ISUP experts published a consensus definition of cribriform pattern highlighting criteria that distinguish it from mimickers. The current study aimed to analyze morphologic features separately to identify those that define the essence of the cribriform pattern. Thirty-two selected photomicrographs were classified by 12 urologic pathologists as: definitely cribriform cancer, probably cribriform, unsure, probably not cribriform, or definitely not cribriform. Consensus was defined as 9/12 agree or disagree, with ≤1 strongly supporting the opposite choice. Final consensus was achieved in 21 of 32 cases. Generalized estimating equation (GEE) model with logit link was fitted to estimate effect of multiple morphologic predictors. Fisher exact test was used for categorical findings. Presence of intervening stroma precluded calling cribriform cancer (p = 0.006). Mucin presence detracted (p = 0.003) from willingness to call cribriform cancer (only 3 cases had mucin). Lumen number was associated with cribriform consensus (p = 0.0006), and all consensus cases had ≥9 lumens. Predominant papillary pattern or an irregular outer boundary detracted (p = NS). Invasive cribriform carcinoma should have absence of intervening stroma, and usually neither papillary pattern, irregular outer boundary, nor very few lumens. Setting the criteria for cribriform will help prevent over- or undercalling this important finding.