We have previously identified tissue inhibitor of metalloproteinases-1 (TIMP-1) as a prognostic marker in glioblastomas. TIMP-1 has been associated with chemotherapy resistance, and CD63, a known TIMP-1-binding protein, has been suggested to be responsible for this effect. The aim of this study was to assess CD63 expression in astrocytomas focusing on the prognostic potential of CD63 alone and in combination with TIMP-1. CD63 expression was investigated immunohistochemically in a cohort of 111 astrocytomas and correlated to tumor grade and overall survival by semi-quantitative scoring. CD63 expression in tumor-associated microglia/macrophages was examined by double-immunofluorescence with ionized calcium-binding adapter molecule 1 (Iba1). The association between CD63 and TIMP-1 was investigated using previously obtained TIMP-1 data from our astrocytoma cohort. Cellular co-expression of TIMP-1 and CD63 as well as TIMP-1 and the tumor stem cell-related markers CD133 and Sox2 was investigated with immunofluorescence. TIMP-1 and CD63 protein interaction was detected by an oligonucleotide-based proximity ligation assay and verified using co-immunoprecipitation. The expression of CD63 was widely distributed in astrocytomas with a significantly increased level in glioblastomas. CD63 levels did not significantly correlate with patient survival at a protein level, and CD63 did not augment the prognostic significance of TIMP-1. Up to 38% of the CD63+ cells expressed Iba1; however, Iba1 did not appear to impact the prognostic value of CD63. A significant correlation was found between TIMP-1 and CD63, and the TIMP-1 and CD63 proteins were co-expressed at the cellular level and located in close molecular proximity, suggesting that TIMP-1 and CD63 could be co-players in glioblastomas. Some TIMP-1+ cells expressed CD133 and Sox2. The present study suggests that CD63 is highly expressed in glioblastomas and that TIMP-1 and CD63 interact. CD63 does not add to the prognostic value of TIMP-1. Co-expression of TIMP-1 and stem cell markers as well as the wide expression of CD63 might suggest a role for TIMP-1 and CD63 in glioblastoma stemness.

It is well known that N-methyl-D-aspartate receptor encephalitis (NMDARE) can be triggered by infectious encephalitis such as herpes simplex virus 1 encephalitis (HSE). However, the incidence of post-HSE NMDARE in Denmark is unknown. We reviewed literature cases and compared these to retrospectively identified cases of post-HSE NMDARE in Denmark, using a national cohort database of autoimmune encephalitis (AE) and two regional databases of infectious encephalitis patients. We identified 80 post-HSE NMDARE cases in the literature, 66% being children, who more often presented movement disorders, decreased consciousness, and sleep disturbances compared to adults. Eight patients with post-HSE NMDARE were identified from the national cohort database of AE, none being children. Forty-four HSE patients were identified from the regional infectious encephalitis databases. Of these, 16 (36%) fulfilled the Graus criteria for probable/definite NMDARE, and eight (18%) presented a prolonged/relapsing disease course. Ten (23%) were tested for AE during hospitalization. Six (14%) had leftover cerebrospinal fluid available for retrospective autoantibody testing. One out of these six patients (17%) harbored NMDARE antibodies. Thus, in total, nine post-HSE NMDARE patients have been identified in Denmark from 2009 to 2021. Comparing the adult Danish patients to the literature, Danish patients were older, but the clinical phenotype and paraclinical findings were similar. Overall, the incidence of adult post-HSE NMDARE in the Region of Southern Denmark was 0.17 per million people per year and only 7% of adult HSE patients in the region were diagnosed with post-HSE NMDARE. Our findings suggest that adult patients are still underdiagnosed and the absence of pediatric cases diagnosed with post-HSE NMDARE in Denmark is highly concerning.

Objective: To introduce salvage prostatectomy in Denmark. Prior to this, no national curative treatment for recurrent prostate cancer following radiation therapy existed in Denmark. This pilot study represent our initial experiences and the feasibility of performing salvage robot-assisted radical prostatectomy for true local, high-risk recurrence after initial therapy with external beam radiation for high-risk prostate cancer. Results: Five patients underwent sRARP between April 2020 and July 2021. All patients were discharged within 48 h and no major complications were observed within 3 months. All patients had unmeasurable PSA (< 0.1 ng/ml) at follow-up 6 months after surgery. One patient with longer follow-up than 6 months experienced biochemical recurrence. At 3-months follow-up all patients reported considerable incontinence, at 6-month follow-up, pad usage decreased to 1 or 2 pads daily. Based on our initial results, the idea to introduce sRARP as a nationwide option remains and further patients will be included to establish the true role of sRARP in patients with recurrence after primary radiotherapy for PCa.

Objective: This study aimed to compare test sensitivity for detecting aggressive prostate cancer and test specificity (measured by reduction in prostate biopsies) between algorithm-triage and standard systematic biopsy in elderly men with suspected prostate cancer. Methods: This randomised controlled trial enrolled men ≥ 70 years old suspected of prostate cancer and randomised them 1:1 to algorithm-triage or standard systematic biopsies. The algorithm arm used a 10-gene mRNA panel from urine and plasma samples, integrated with clinical characteristics and PSA measurements to predict prostate cancer with International Society of Urological Pathology grade group ≥ 2. Patient-reported outcomes measures were collected using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores or subdomains throughout a 24-month follow-up. ClinicalTrials.gov: NCT04079699. Results: A total of 202 men were included between October 2019 and September 2021. The study was terminated early due to algorithm underperformance. The algorithm-triage arm detected fewer indolent cancers (7.9% vs. 19%, absolute difference −10.9 percentage points, 95% confidence interval [CI]: −21.0 to −1.0 pp, P = 0.039) but also fewer clinically significant cancers (26% vs. 40%, absolute difference −13.9 percentage points, 95% CI: −27.6 to −0.1 pp, P = 0.051) compared to systematic biopsy. Patient-reported outcomes showed no significant between-group differences in FACT-P scores or subdomains throughout 24-month follow-up (differences 0.1–2.2 points, all P > 0.05), indicating comparable quality of life. Conclusion: The biomarker-based algorithm-triage reduced biopsy numbers but also detected fewer ­clinically significant prostate cancers. Quality of life was comparable between approaches.