Childhood Sjögren syndrome: features of an international cohort and application of the 2016 ACR/EULAR classification criteria.

OBJECTIVE: Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population. METHODS: An international workgroup retrospectively collected cases of Sjögren syndrome diagnosed under 18 years of age from 23 centres across eight nations. We analysed patterns of symptoms, diagnostic workup, and applied the 2016 ACR/EULAR classification criteria. RESULTS: We identified 300 children with Sjögren syndrome. The majority of patients n = 232 (77%) did not meet 2016 ACR/EULAR classification criteria, but n = 110 (37%) did not have sufficient testing done to even possibly achieve the score necessary to meet criteria. Even among those children with all criteria items tested, only 36% met criteria. The most common non-sicca symptoms were arthralgia [n = 161 (54%)] and parotitis [n = 140 (47%)] with parotitis inversely correlating with age. CONCLUSION: Sjögren syndrome in children can present at any age. Recurrent or persistent parotitis and arthralgias are common symptoms that should prompt clinicians to consider the possibility of Sjögren syndrome. The majority of children diagnosed with Sjögren syndromes did not meet 2016 ACR/EULAR classification criteria. Comprehensive diagnostic testing from the 2016 ACR/EULAR criteria are not universally performed. This may lead to under-recognition and emphasizes a need for further research including creation of paediatric-specific classification criteria.

Beef Nutritional Characteristics, Fat Profile and Blood Metabolic Markers from Purebred Wagyu, Crossbred Wagyu and Crossbred European Steers Raised on a Fattening Farm in Spain.

A high intramuscular fat content characterizes Wagyu (WY) cattle breed. Our objective was to compare beef from WY, WY-by-Angus, or Wangus (WN) steers with European, Angus-by-Charolais-Limousine crossbred steers (ACL), considering metabolic biomarkers pre-slaughtering and nutritional characteristics, including health-related indexes of the lipid fraction. The fattening system with olein-rich diets and no exercise restriction included 82 steers, 24 WY, 29 WN, and 29 ACL. The slaughter ages and weights were (median and interquartile range) 38.4 mo.-old (34.9-40.3 mo.) and 840 kg (785-895 kg) for WY; for WN, 30.6 mo. (26.9-36.5 mo.) and 832 kg (802-875 kg), and for ACL steers, 20.3 mo.-old (19.0-22.7 mo.) and 780 kg (715-852 kg). Blood lipid-related metabolites, except for non-esterified fatty acids (NEFA) and low-density level cholesterol (LDL), were higher in WY and WN than in ACL, while glucose was lower in WY and WN. Leptin was higher in WN than in ACL. Pre-slaughtering values of plasma HDL underscored as a possible metabolic biomarker directly related to beef quality. The amino-acid content in beef did not differ among experimental groups, except for more crude protein in ACL. Compared to ACL, WY steers showed higher intramuscular fat in sirloin (51.5 vs. 21.9%) and entrecote (59.6 vs. 27.6%), more unsaturated fatty acids in entrecote (55.8 vs. 53.0%), and more oleic acid in sirloin (46 vs. 41.3%) and entrecote (47.5 vs. 43.3%). Compared to ACL entrecote, WY and WN showed better atherogenic (0.6 and 0.55 vs. 0.69), thrombogenicity (0.82 and 0.92 vs. 1.1), and hypocholesterolemic/hypercholesterolemic index (1.9 and 2.1 vs. 1.7). Therefore, beef's nutritional characteristics depend on breed/crossbred, slaughtering age and cut, with WY and WN entrecote samples showing a healthier lipid fraction.

Comparison of Pure and Crossbred Japanese Black Steers in Growth Performance and Metabolic Features from Birth to Slaughter at a Spanish Fattening Farm.

Japanese Black (Wagyu) cattle produce high-quality beef. However, whether Wagyu steers can be profitably raised under conditions different than the traditional Japanese ones remains unclear. From 2018 to 2020, we raised 262 Wagyu purebred steers, 103 Wagyu-by-Angus (Wangus) crossbred steers, and 43 Angus-by-European (ACL) crossbred steers on a Spanish farm with high welfare standards and a locally sourced, high-olein diet. Factors and factors' interactions impacting steer growth were analyzed using generalized linear models. ACL steers grew faster than the other two groups, with Wangus showing intermediate fattening and muscle development. Average daily weight gains (kg/day) were 0.916 for Wagyu, 1.046 for Wangus, and 1.293 for ACL during the weaning to growing period, and 0.628 for Wagyu, 0.64 for Wangus, and 0.802 for ACL during the growing to fattening phase. ACL showed the lowest marbling rates. Wagyu and Wangus usually showed higher cholesterol, triglycerides, and high-density lipoprotein than ACL. ACL calves may experience greater stress at weaning, as suggested by higher glucose, lactate, and ß-hydroxybutyrate than the other groups. The results suggest that Wagyu and Wangus steers showed adequate growth, health, and metabolic development in this type of production system, with Wagyu purebreds probably being more profitable than Wangus crossbreeds.

MOET Efficiency in a Spanish Herd of Japanese Black Heifers and Analysis of Environmental and Metabolic Determinants.

Multiple ovulation and embryo transfer (MOET) systems have been intensively implemented in Japanese Black cattle in Japan and to create Japanese Black herds out of these areas. Environmental conditions influence MOET efficiency. Thus, we describe results of 137 in vivo, non-surgical embryo flushings performed between 2016-2020, in a full-blood Japanese Black herd kept in Spain and the possible effects of heat, year, bull, donor genetic value, and metabolic condition. Additionally, 687 embryo transfers were studied for conception rate (CR) and recipient related factors. A total of 71.3% of viable embryos (724/1015) were obtained (5.3 ± 4.34/flushing). Donor metabolites did not affect embryo production (p > 0.1), although metabolite differences were observed over the years, and by flushing order, probably related to the donor age. CR was not affected by embryo type (fresh vs. frozen), recipient breed, and whether suckling or not suckling (p > 0.1). CR decreased significantly with heat (44.3 vs. 49.2%; (p = 0.042)) and numerically increased with recipient parity and ET-number. Pregnant recipients showed significantly higher levels of cholesterol-related metabolites, glucose, and urea (p < 0.05). Therefore, adequate MOET efficiency can be achieved under these conditions, and heat stress should be strongly avoided during Japanese Black embryo transfers. Moreover, recipients' metabolites are important to achieve pregnancy, being probably related to better nutrient availability during pregnancy.

Feasibility of in-office MRI-targeted partial gland cryoablation for prostate cancer: an IDEAL stage 2A study.

OBJECTIVES: Cryoablation for prostate cancer is typically performed under general anaesthesia. We explore the safety, feasibility and costs of in-office MRI-targeted prostate partial gland cryoablation (PGC) under local anaesthesia. We hypothesise that an office-based procedure under local anaesthesia may yield greater patient convenience and lower health costs with similar outcomes to a general anaesthesia approach. DESIGN/PARTICIPANTS/SETTING/INTERVENTIONS: Retrospective study of men diagnosed with clinically significant prostate cancer (grade group (GG) ≥2) who elected to undergo in-office PGC under local anaesthesia. MAIN OUTCOME MEASURES: A total of 55 men with GG ≥2 prostate cancer underwent PGC under local anaesthesia, and 35 of 43 men (81.4%) who attained ≥6 months of follow-up post-treatment underwent MRI-targeted surveillance biopsy. We used MRI findings and targeted biopsy to characterise post-PGC oncological outcomes. Complications were categorised using Common Terminology Criteria for Adverse Events (CTCAE). Expanded Prostate Cancer Index-Clinical Practice was used to characterise urinary and sexual function scores at baseline, 4 and 9 months post-PGC. Time-driven activity-based costing was used to determine healthcare costs of in-office PGC. RESULTS: Five (9.1%) men experienced CTCAE score 3 adverse events. Urinary and sexual function did not change significantly from baseline to 4 months (p=0.20 and p=0.08, respectively) and 9 months (p=0.23 and p=0.67, respectively). Twenty-two men (62.9%) had no cancer or GG1 and 13 (37.1%) men had GG≥2 on post-PGC biopsy. Moreover, the median cost of in-office PGC was US$4,463.05 (range US$4,087.19-US7,238.16) with disposables comprising 69% of the cost. CONCLUSIONS: In-office PGC is feasible under local anaesthesia with favourable functional outcome preservation and adverse events profile at significantly lower costs compared with a general anaesthesia approach.

Race and prostate imaging: implications for targeted biopsy and image-based prostate cancer interventions.

PURPOSE: For men with an elevated prostate-specific antigen (PSA), there is a strong evidence for prostate MRI to assess the risk of clinically significant prostate cancer (CSPC) and guide targeted-biopsy interventions. Prostate MRI is assessed using the Prostate Imaging-Reporting and Data System (PI-RADS), which is scored from 1 to 5. Equivocal or suspicious findings (PI-RADS 3-5) are recommended for subsequent targeted biopsy, for which the risk of infection and sepsis is increasing. However, PI-RADS was developed primarily in men of European descent. We sought to elucidate PI-RADS and MRI-targeted biopsy outcomes in Asian men, a rapidly growing population in the USA, Europe, Australia and internationally. MATERIALS AND METHODS: A prospective cohort of 544 men with elevated PSA without a diagnosis of prostate cancer who underwent MRI-targeted biopsy at our institution from January 2012 to December 2018 was analyzed. We categorized the cohort by self-designated race then used a validated algorithm which uses surname lists to identify a total of 78 (14%) Asian-Americans. The primary outcome was the likelihood of diagnosing CSPC (Gleason grade group >1) in Asian-Americans versus non-Asian-Americans. Multivariable logistic regression was used to determine the association of demographic and other characteristics with CSPC. RESULTS: Overall, MRI-targeted biopsy identified CSPC in 17% of Asian-American men versus 39% of non-Asian-American men (p<0.001). Notably for PI-RADS 3, only 6% of Asian-Americans versus 15% of others were diagnosed with CSPC. In adjusted analyses, Asian-American men were less likely to be diagnosed on MRI-targeted biopsy with CSPC (OR 0.30, 95% CI 0.14 to 0.65, p=0.002) and indolent prostate cancer (OR 0.37, 95% CI 0.15 to 0.91, p=0.030) than other races. Regardless of race those who were biopsy naïve were more likely (OR 2.25, 95% CI 1.45 to 3.49, p<0.001) to be diagnosed with CSPC. CONCLUSION: We found that PI-RADS underperforms in Asian-American men. For instance, only 2 of 35 (6%) Asian-American men with PI-RADS 3 were diagnosed with CSPC on MRI targeted biopsy. This has significant implications for overuse of diagnostic and image-guided interventional approaches in Asian-Americans, given the increasing risk of infectious complications from biopsy. Additional validation studies are needed to confirm our findings.

A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers.

PURPOSE: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop de novo or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth. PATIENTS AND METHODS: Sixty men were treated with alisertib 50 mg twice daily for 7 days every 21 days. Eligibility included metastatic prostate cancer and at least one: small-cell neuroendocrine morphology; ≥50% neuroendocrine marker expression; new liver metastases without PSA progression; or elevated serum neuroendocrine markers. The primary endpoint was 6-month radiographic progression-free survival (rPFS). Pretreatment biopsies were evaluated by whole exome and RNA-seq and patient-derived organoids were developed. RESULTS: Median PSA was 1.13 ng/mL (0.01-514.2), number of prior therapies was 3, and 68% had visceral metastases. Genomic alterations involved RB1 (55%), TP53 (46%), PTEN (29%), BRCA2 (29%), and AR (27%), and there was a range of androgen receptor signaling and NEPC marker expression. Six-month rPFS was 13.4% and median overall survival was 9.5 months (7.3-13). Exceptional responders were identified, including complete resolution of liver metastases and prolonged stable disease, with tumors suggestive of N-myc and Aurora-A overactivity. Patient organoids exhibited concordant responses to alisertib and allowed for the dynamic testing of Aurora-N-myc complex disruption. CONCLUSIONS: Although the study did not meet its primary endpoint, a subset of patients with advanced prostate cancer and molecular features supporting Aurora-A and N-myc activation achieved significant clinical benefit from single-agent alisertib.