HLA reduction of human T cells facilitates generation of immunologically multicompatible cellular products.

ABSTRACT: Adoptive cellular therapies have shown enormous potential but are complicated by personalization. Because of HLA mismatch, rejection of transferred T cells frequently occurs, compromising the T-cell graft's functionality. This obstacle has led to the development of HLA knock-out (KO) T cells as universal donor cells. Whether such editing directly affects T-cell functionality remains poorly understood. In addition, HLA KO T cells are susceptible to missing self-recognition through natural killer (NK) cells and lack of canonical HLA class I expression may represent a safety hazard. Engineering of noncanonical HLA molecules could counteract NK-cell recognition, but further complicates the generation of cell products. Here, we show that HLA KO does not alter T-cell functionality in vitro and in vivo. Although HLA KO abrogates allogeneic T-cell responses, it elicits NK-cell recognition. To circumvent this problem, we demonstrate that selective editing of individual HLA class I molecules in primary human T cells is possible. Such HLA reduction not only inhibits T-cell alloreactivity and NK-cell recognition simultaneously, but also preserves the T-cell graft's canonical HLA class I expression. In the presence of allogeneic T cells and NK cells, T cells with remaining expression of a single, matched HLA class I allele show improved functionality in vivo in comparison with conventional allogeneic T cells. Since reduction to only a few, most frequent HLA haplotypes would already be compatible with large shares of patient populations, this approach significantly extends the toolbox to generate broadly applicable cellular products.

Age at surgery is not a prognostic factor for the AdVance-XP male sling efficacy: A post-hoc analysis of a prospective 7-year multicentric study.

OBJECTIVE: To evaluate the factor age at the surgery on long-term postoperative outcomes in patients with postprostatectomy incontinence (PPI) after AdVance XP transobturator male sling implantation. METHODS: A total of 115 male patients with PPI, who had undergone AdVance XP sling implantation, were included. Patients had PPI with endoscopically confirmed good sphincteric-contractility and a positive coaptive response. Kruskal-Wallis test with Dunn post-hoc tests were used to analyze the postoperative outcome differences between the patient groups aged less than 66, 66-75, and over greater than 75 years. Outcome measures were the 24 h pad test, the number of daily pads used, the International Consultation on Incontinence Questionnaire short form (ICIQ-SF), International Quality of Life Score (IQOL), Patient Global Impression of Improvement (PGI-I), International Index of Erectile Function-5 (IIEF-5), International Prostate Symptom Score (IPSS), and Visual Analog Scale scores. Observation time points were 3, 6, 12, 24, 36, 48, 60, and 84 months after surgery. RESULTS: Between the age groups, there was no difference in the success rate of the procedure (defined as 0 pads/24 h and less than 5 g in the 24-h pad test) at any point in time. Subjective parameters measures using the ICIQ-SF, PGI-I, IQOL, and IPSS scores showed no differences between the two cohorts. Only erectile function (IIEF-5 score) was lower in older patients in comparison to the cohort aged less than 66 years (p < 0.05 at 3, 6, 12, 24, 36, and 48 months). CONCLUSIONS: The present study complements the European multicentre AdVance XP follow-up study. Here, we show that age at surgery does not affect the objective success, subjective success, or the complication rate. Thus, we do not recommend factoring in chronological age into surgical selection criteria for the AdVance XP implantation.

Mapping Telemedicine in German Private Practice Urological Care: Implications for Transitioning beyond the COVID-19 Pandemic.

BACKGROUND: There are limited data on the use and concern of telemedicine among German urologists, and thus, there are no established guidelines for telemedical diagnosis, treatment, and prevention of urological indications. METHODS: An anonymized survey was conducted among German private practice urologists during the 2019 coronavirus disease (COVID-19) pandemic. The χ2 test, Mann-Whitney U-test, and Kruskal-Wallis test were used for statistical analysis. RESULTS: 257 urologists were included in the final analysis. Thirty-five (14.0%) of urologists had used telemedicine as part of their consultation, and 221 (86.0%) had not used telemedicine. There was no difference between telemedicine adoption rates between rural and urban settings. Telemedicine users were significantly more satisfied with the information they had received regarding telemedicine issues. Users saw the greatest barrier to telemedicine that patients do not take up the offer of telemedicine. Nonusers were most concerned with unclear indications for telemedicine followed by lesser reimbursements during telemedicine than in-person visitations. Users were significantly more likely to use telemedicine beyond the COVID-19 pandemic. Urologists, who wanted to use the service in the future, wanted an active support by the German society of urology and guidelines for telemedicine. Last, users and nonusers preferred telemedicine for non-acute chronic diseases and follow-up visitations. CONCLUSION: Despite the COVID-19 pandemic, telemedicine remains a rarely used service among German private practice urologists. Ultimately, to overcome the current challenges, urologists require an active support for the service through the German Society of Urology and telemedical guidelines.