An international multicentre randomised controlled trial of en bloc resection of bladder tumour vs conventional transurethral resection of bladder tumour: first results of the en bloc resection of urothelium carcinoma of the bladder (EBRUC) II trial.

OBJECTIVES: To determine the safety and oncological advantages of en bloc resection of bladder tumour (ERBT) vs conventional transurethral resection of bladder tumour (cTURBT) in terms of resection quality, staging quality, and safety. PATIENTS AND METHODS: We conducted a single-blinded randomised controlled trial at seven European hospitals with the following inclusion criteria: first diagnosis of non-muscle-invasive bladder cancer, no singular carcinoma in situ, and tumour size >4.3 mm. Patients were randomised intraoperatively in a 1:1 ratio to either the ERBT or cTURBT group. Outcome analysis was performed using the chi-square test, t-test, and multivariate regression analysis. RESULTS: A total of 97 patients were randomised into the study (cTURBT = 40, ERBT = 57). A switch to cTURBT was necessary in two patients (3.5%) and 11.5% of the screened patients were preoperatively excluded for ERBT. There was no difference in the specimen presence of detrusor muscle with 73.7% in cTURBT and 67.3% in ERBT specimens (P = 0.69). There were no significant differences in mean operative time (ERBT 27.6 vs cTURBT 25.4 min, P = 0.450) or mean resection time (ERBT 16.3 vs cTURBT 15.5 min, P = 0.732). Overall the complication rate did not differ significantly (ERBT 18.2% vs cTURBT 7.5%, P = 0.142). Bladder perforations occurred significantly more often in the ERBT group (ERBT seven vs cTURBT none, P = 0.020). R0 status was reported more often after ERBT, whilst a second resection was significantly less frequent after ERBT (P = 0.018). Recurrence rates were comparable for both techniques after 6 months of follow-up. CONCLUSION: The feasibility of ERBT is higher than previously reported. Whereas other perioperative and safety parameters are comparable to cTURBT, bladder perforations occurred significantly more often in the ERBT group and raised safety concerns. This is why this trial was terminated.

The early learning curve of the bipolar enucleation of the prostate: a multicenter cohort study.

OBJECTIVES: To evaluate the early learning curve of BipolEP (Bipolar Enucleation of the Prostate). SUBJECTS/PATIENTS AND METHODS: We conducted a retrospective, multicenter analysis of surgical and functional outcomes of patients treated with BipolEp for BPO (benign prostatic obstruction). We evaluated the first 20 cases of BipolEp performed by four different surgeons in three different countries. The following baseline parameters were obtained: age, IPSS, indwelling catheter, transrectal measured prostate volume, post void residual volume (PVR) and uroflowmetry. The learning curve was analysed based on perioperative parameters and the influence of perioperative parameters was correlated with the sequence of BipolEp cases. RESULTS: 84 BipolEp operations performed by 4 different surgeons in their early learning curve were studied. Mean prostate volume was 75 ml, 39% of cases had an indwelling catheter and the average operating time was 101 min. Three out of four surgeons performed at least 50% of successful operations according to Trifecta (complete enucleation and morcellation < 90 min., no conversion to TUR-P). Conversion rate to TURP was 11.9% in total which however was driven by a single surgeon with an almost 50% conversion rate. Mean enucleated prostate was 33.3 gr (18-54.5). Intraoperative complications and reported stress incontinence ranged from 0 to 38.1%. At six-weeks review, the IPPS improved by 12.5 (8-16) points and Qmax by 208% (109.8-266.7). Uroflowmetry outcomes correlated with the sequence of cases with a linear improvement during 20 consecutive cases (p = 0.018) in all centres. Major complications (Clavien Dindo ≥ 3) were rare (4.8%) and comparable between the groups. CONCLUSION: Surgeons starting to learn BipolEp can expect to be able to achieve a linear improvement in Uroflow at the six-week postoperative evaluation after 20 consecutive cases. BipolEp can be successfully performed during the early learning curve with an acceptable rate of conversion to standard TUR-P.

Uretero-neocystostomy: a retrospective comparison of open, laparoscopic and robotic techniques.

BACKGROUND: Uretero-neocystostomy (UNC) is the gold-standard for distal-ureter repair. Whether the surgery should be conducted minimally invasive (laparoscopic (LAP), robotic RAL)) or open remains unanswered by the literature. METHODS: Retrospective analysis of surgical outcome of patients treated with UNC for distal ureteral stenosis (January 2012 - October 2021). Patient demographics, estimated blood loss (EBL), surgical technique, operative time, complications and length of hospital stay (LOS) were recorded. During the follow-up period, patient underwent renal ultrasound and kidney function tests. Success was defined as relieve of symptoms or no findings of obstruction needing urine drainage. RESULTS: 60 patients were included (9 RAL, 25 LAP, 26 open). The different cohorts were similar of age, gender, American Society of Anesthesiologists (ASA) score, body-mass index and history of prior treatment of the ureter. No intraoperative complications were detected in all groups. There was no conversion to open surgery in the RAL group, whereas one was found in the LAP arm. Six patients had a recurrent stricture, but with no significant difference between the cohorts. EBL was not different between the groups. LOS was significantly lower in the RAL + LAP group compared to open (7 vs. 13 days, p = 0.005) despite significantly longer operating times (186 vs. 125.5 min, p = 0.005). CONCLUSION: Minimal invasive UNC, especially RAL, is a feasible and safe surgical method and provides similar results in terms of success rates in comparison to open approach. A shorter LOS could be detected. Further prospective studies need to be done.

Electrosurgery or laser for benign prostatic enlargement: trumpcard or pitfalls.

PURPOSE OF REVIEW: To summarize and comment on publications of the last 2 years in the field of endoscopic surgery for benign prostatic enlargement, focusing on similarities and differences of laser and electrosurgery. RECENT FINDINGS: Because of good hemostasis and safety, invasive endoscopic surgery has evolved to a choice of treatment for vulnerable patients with ongoing antithrombotic medication and in same-day surgery. Recent publications show a good perioperative course and no deterioration in the postoperative outcome. Furthermore, alterations to the original surgical techniques of resection, enucleation, and vaporization have increased the preservation rate for antegrade ejaculation, advancing them to an appealing choice of treatment for sexually active men. Favorable outcomes can be achieved in both laser and electrosurgery. Only the choice of the surgical technique determines the outcome. SUMMARY: Various invasive endoscopic surgical techniques are available, offering different advantages and disadvantages for the patient. All of them can be performed with laser and electrosurgery. Therefore, focusing on the proper choice of surgical technique instead of the energy source will guarantee the patient to benefit most.

En bloc re-resection of high-risk NMIBC after en bloc resection: results of a multicenter observational study.

PURPOSE: To investigate the role of en bloc re-resection (EBRS) in patients who had undergone previous en bloc resection for high-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: An international, multicenter, observational retrospective analysis of prospectively collected data. Patients with a high-risk NMIBC who had previously undergone en bloc resection were scheduled for EBRS of the resected area after 40 days. The primary outcome was the presence of residual tumor or recurrence-free survival. RESULTS: Overall, 78 patients underwent EBRS. Only five (6.41%) residual cancers were found: one patient had a pTa G3 (1.28%) cancer and four (5.13%) had a pTis. The detrusor muscle was preserved in all samples. Only one patient had a positive margin on EBRS. No procedure called for a conversion to traditional re-TURBT. No patient experienced bladder perforation or other intra-operative complications. The recurrence rate at the first follow-up cystoscopy (RRFF-C at 3 months) was 3.85% (three patients). The median follow-up period was 30.8 months (range 6.9-76.0 months). In univariate analysis, the only predictor of recurrence was grade. Overall we observed 11 recurrences. Only one tumor progressed to T2 MIBC. CONCLUSIONS: The low rates of residual tumor, recurrence, and progression seem to raise doubts about the efficacy of EBRS in patients who have previously undergone en bloc resection. EBRS appears to be a feasible and safe procedure with a low rate of complications. However, further data will be needed before EBRS can be used in clinical trials or recommended as a treatment modality.

Is real-time PCR the correct method to evaluate the incidence of human papillomavirus in prepuces of asymptomatic boys and men?

OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) in prepuces of asymptomatic boys and men, the present study was designed. METHODS: Two hundred and fifty male prepuce specimens who underwent circumcision due to phimosis were collected. Samples were subdivided into groups regarding their age: children (group I, 0-10 years), adolescents (group II, 11-20 years) and adults (group III, >20 years). HPV High Screen Real-TM Quant 2x kit detecting HPV 6 and 11 (low risk) as well as another kit for identification of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 (high risk) were used. Additionally, a Taq Man assay has been designed targeting the L1 gene of HPV 6, 11, 16 and 18. RESULTS: Evaluating the number of low-risk HPV subtypes, we found HPV 6 and 11 in 5.3 % of samples (n = 12/226). Concerning high-risk HPV, we found a positivity in 4 % of samples (n = 9/224). In contrast to low-risk data where no age distribution was observed, we found an age-specific accumulation of high-risk HPV subtypes in the children group (n = 6/9). A second independent assay (Taq Man PCR assay) measuring HPV 6, 11, 16 and 18 of all positive samples confirmed only the high-risk HPV subtypes of the Real-TM Quant 2x assay. CONCLUSIONS: Our study provides evidence that qPCR estimation for HPV infection obviously underestimates the incidence rate of infected prepuces in boys and men with phimosis. Contrary, an overestimation of the HPV infection rate with the in situ hybridization method of phimotic prepuces cannot be excluded.

A Matter of Trust: Confidentiality in Therapeutic Relationships during Psychological and Medical Treatment in Children and Adolescents with Mental Disorders.

Background: Confidentiality is a crucial ethical principle in therapy, particularly for children and adolescents, yet their perception of it remains understudied. We aimed to explore minors' perspectives and attributions on confidentiality in psychological and medical treatment. Methods: We interviewed 11 pediatric patients aged 7 to 15 and used reflexive thematic analysis to analyze their responses. Results: Four main themes were extracted from the data: (1) confidentiality and uncertainty regarding what information will be shared with clinicians and parents; (2) consequences of breaching confidentiality, encompassing breaches of confidentiality in the past and their negative effects on interactions with parents and health professionals; (3) exceptions to confidentiality, including understanding the limits of confidentiality; and (4) autonomy and self-determination, reflecting the desire for involvement in medical decisions. Conclusions: Explanations about confidentiality rules and limits, especially with younger children, are crucial. This is particularly important because it is fundamental to promote children's development and self-determination through increasing autonomy, as well as to provide a sense of security and respect through transparent rules. A single educational session on confidentiality at the outset of therapy is insufficient; ongoing conversations are needed to reinforce understanding and promote autonomy.

Discriminating Malignant from Benign Testicular Masses Using Multiparametric Magnetic Resonance Imaging-A Prospective Single-Center Study.

Objective: The objective of this study was to prospectively assess the extent to which magnetic resonance imaging (MRI) can differentiate malignant from benign lesions of the testis. Materials and Methods: All included patients underwent multiparametric testicular MRI, including diffusion-weighted imaging (DWI) and subtraction dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Subsequently, all patients underwent a histopathological examination via orchiectomy or testicular biopsy/partial resection. The Kolmogorov-Smirnov test, t-test, Mann-Whitney U test, Fisher's exact test, and logistic regression were applied for statistical analysis. Results: We included 48 male patients (median age 37.5 years [range 18-69]) with testicular tumors. The median tumor size on MRI was 2.0 cm for malignant tumors and 1.1 cm for benign tumors (p < 0.05). A statistically significant difference was observed for the type (type 0-III curve, p < 0.05) and pattern of enhancement (homogeneous, heterogeneous, or rim-like, p < 0.01) between malignant and benign tumors. The minimum apparent diffusion coefficient (ADC) value was 0.9 for benign tumors and 0.7 for malignant tumors (each ×103 mm2/s, p < 0.05), while the mean ADC was 0.05. The mean ADC value was significantly lower for malignant tumors; the mean ADC value was 1.1 for benign tumors and 0.9 for malignant tumors (each ×103 mm2/s, p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of multiparametric MRI for differentiating malignant from benign testicular lesions were 94.3%, 76.9%, 91.7%, and 83.3%, respectively. The surgical procedures performed included orchiectomy (n = 33; 71.7%) and partial testicular resection (n = 11; 23.9%). Histopathology (HP) revealed malignancy in 35 patients (72.9%), including 26 with seminomas and 9 with non-seminomatous germ cell tumors (NSGCTs). The HP was benign in 13 (27.1%) patients, including 5 with Leydig cell tumors. Conclusions: Malignant and benign tumors differ in MRI characteristics in terms of the type and pattern of enhancement and the extent of diffusion restriction, indicating that MRI can be an important imaging modality for the accurate diagnosis of testicular lesions.

Real-Time Dosimetry in Endourology: Tracking Staff Radiation Risks.

BACKGROUND: To retrospectively investigate scatter radiation (SCR) exposure among staff in the endourology operating theatre. METHODS: During surgeries under fluoroscopic guidance, five professional groups (urological surgeon [US], surgical nurse [SN], assistant surgical nurse [ASN], anaesthetist [A], and anaesthesia care [AC]) wore real-time dosimeters (Philips DoseAware System) on their head and chest over lead aprons between July 2023 and February 2024. The SCR data were analysed and correlated with procedural and patient factors. RESULTS: In total, 249 procedures were performed, including 86 retrograde intrarenal surgeries and 10 percutaneous nephrolithotomies. Median SCR exposure was 38.81, 17.20, 7.71, 11.58, 0.63, 0.23, 0.12, and 0.15 Microsievert (µSv) for US chest (USC), US head (USH), SN chest (SNC), SN head (SNH), A chest (AC), AC chest (ACC), ASN chest (ASNC), and ASN head (ASNH), respectively. There was a significant correlation between DAP and SCR doses detected by USC, USH, SNC, SNH, AC, and ACC dosimeters (p < 0.05). The median chest-to-eye conversion factor (CECF) was 2.11 for the US and 0.71 for the SN. CONCLUSIONS: This study, using real-time dosimetry, is among the first to assess staff occupational SCR exposure in endourology. It highlights a substantial SCR exposure, indicating an occupational health hazard that warrants further investigation.

Functional Outcome and Safety of Endoscopic Treatment Options for Benign Prostatic Obstruction (BPO) in Patients ≥ 75 Years of Age.

Background: The selection of suitable patients for the surgical treatment of benign prostatic obstruction (BPO) is a challenge in persons ≥75 years of age. Methods: After a systematic literature search of PubMed, 22 articles were included in this review. Clinical and functional parameters were evaluated statistically. Results: The mean age of the patients was ≥79 years. The mean duration of postoperative catheterization ranged between 2 (d) (ThuLEP, thulium laser enucleation of the prostate) and 4.4 days (TURP, transurethral resection of the prostate). Complication rates ranged between 6% (HoLAP, holmium laser ablation of the prostate) and 34% (PVP, photoselective vaporization of the prostate); the maximum rate of severe complications was 4% (TURP). The mean postoperative maximal urinary flow (Qmax) in mL/sec. ranged between 12.9 mL/sec. (HoLAP) and 19.8 mL/sec (Hol-TUIP, holmium laser transurethral incision of the prostate). The mean quality of life (QoL) score fell from 4.7 ± 0.9 to 1.8 ± 0.7 (HoLEP), from 4.1 ± 0.4 to 1.9 ± 0.8 (PVP), from 5.1 ± 0.2 to 2.1 ± 0.2 (TURP), and from 4 to 1 (ThuVEP, thulium laser vapoenucleation of the prostate). Pearson's correlation coefficient (r) revealed a positive linear correlation between age and inferior functional outcome (higher postoperative International Prostate Symptom Score (IPSS) [r = 0.4175]), higher overall complication rates (r = 0.5432), and blood transfusions (r = 0.4474) across all surgical techniques. Conclusions: This meta-analysis provides the summary estimates for perioperative and postoperative functional outcome and safety of endoscopic treatment options for BPO in patients ≥ 75 years of age. Of particular importance is that all surgical techniques significantly improve the postoperative quality of life of patients in this age group compared to their preoperative quality of life.

[Imaging in nephroureterolithasis]. / Bildgebung bei Nephroureterolithiasis.

In the acute diagnostics of a suspected nephroureterolithiasis, ultrasonography should be the examination modality of choice. In cases of suspected urolithiasis, unclear flank pain with fever or in cases of a solitary kidney, a noncontrast computed tomography (CT) scan should always subsequently be performed. If the sonography findings are inconclusive in pregnant women a magnetic resonance imaging (MRI) examination can be considered. If there are indications for urinary diversion, a retrograde imaging study should be performed as part of the urinary diversion. This or CT imaging is also suitable for preinterventional imaging before shock wave lithotripsy, percutaneous nephrolithotomy or ureteroscopy. Postinterventional imaging is not always necessary and sonography is often sufficient. In a conservative treatment approach an abdominal plain X­ray can be used for follow-up assessment.

Effects of COVID-19 Infection on Spermatogenesis, Oxidative Stress and Erectile Function.

BACKGROUND: Our aim was to evaluate the effect of COVID-19 infection on male fertility and sexual function. METHODS: Thirty-one patients were investigated over a mean follow-up of 90 days (22-527) after a COVID-19 infection. Erectile dysfunction (ED), blood tests for sexual hormones, semen analysis including analysis of oxidative stress (OS), as well as COVID-19 antibody titer and the nasal COVID-19 PCR test were evaluated pre- and post-infection. RESULTS: Five patients reported a mild de novo ED (16.13%). One patient had a de novo positive mixed antiglobulin reaction test after the infection. We found no significant difference between pre-COVID-19 and post-COVID-19 spermiogram parameters (p = 0.815). OS showed no significant association with COVID-19 infection, but with pathological spermiogram categories, sperm concentration, total sperm count, testis volume, FSH and testosterone. CONCLUSION: COVID-19 infection does not appear to affect sperm quality and OS negatively in the intermediate term. Further investigations will be needed to assess the potential long-term effects of the infection and vaccination on male sexual function and fertility.

Subsets of preoperative sex hormones in testicular germ cell cancer: a retrospective multicenter study.

Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: 'neutral' (n = 228) with normal sex hormone homeostasis, 'testicle' (n = 91) with elevated T and E2, low pituitary hormones, and finally 'pituitary' subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones.

Neoadjuvant Chemotherapy before Nephroureterectomy in High-Risk Upper Tract Urothelial Cancer: A Systematic Review and Meta-Analysis.

Neoadjuvant chemotherapy is a well-established concept in muscle-invasive bladder cancer with known advantages in overall survival. Phase II trials show encouraging response rates for neoadjuvant immunotherapy before radical surgery in urothelial cancer. There is no recommendation for neoadjuvant therapy in upper tract urothelial carcinoma before nephroureterectomy. Our aim was to assess the available data on neoadjuvant chemotherapy and immunotherapy before nephroureterectomy in patients with high-risk upper tract urothelial carcinoma in terms of pathological downstaging and oncological outcomes. Two investigators screened PubMed/Medline for comparative trials in the English language. We identified 368 studies and included eleven investigations in a systematic review and meta-analysis for neoadjuvant chemotherapy and control groups. There were no comparative trials investigating immunotherapy in this setting. All 11 studies reported on overall pathological downstaging with a significant effect in favor of neoadjuvant chemotherapy (OR 5.17; 95%CI 3.82; 7.00). Pathological complete response and non-muscle invasive disease were significantly higher in patients receiving neoadjuvant chemotherapy (OR 12.07; 95%CI 4.16; 35.03 and OR 1.62; 95%CI 1.05; 2.49). Overall survival and progression-free survival data analysis showed a slight benefit for neoadjuvant chemotherapy. Our results show that neoadjuvant chemotherapy is effective in downstaging in upper urinary tract urothelial carcinoma. The selection of patients and chemotherapy regimens are unclear.

From Interferon to Checkpoint Inhibition Therapy-A Systematic Review of New Immune-Modulating Agents in Bacillus Calmette-Guérin (BCG) Refractory Non-Muscle-Invasive Bladder Cancer (NMIBC).

BACKGROUND: In Bacillus Calmette-Guérin (BCG) refractory non-muscle-invasive bladder cancer (NMIBC), radical cystectomy is the gold standard. The advent of immune checkpoint inhibitors (CPIs) has permanently changed the therapy landscape of bladder cancer (BC). This article presents a systematic review of immune-modulating (IM) therapies (CPIs and others) in BCG-refractory NMIBC. METHODS: In total, 406 articles were identified through data bank research in PubMed/Medline, with data cutoff in October 2021. Four full-text articles and four additional congress abstracts were included in the review. RESULTS: Durvalumab plus Oportuzumab monatox, Pembrolizumab, and Nadofaragene firadenovec (NF) show complete response (CR) rates of 41.6%, 40.6%, and 59.6% after 3 months, with a long-lasting effect, especially for NF (12-month CR rate of 30.5%). Instillations with oncolytic viruses such as NF and CG0070 show good efficacy without triggering significant immune-mediated systemic adverse events. Recombinant BCG VPM1002BC could prove to be valid as an alternative to BCG in the future. The recombinant pox-viral vector vaccine PANVAC™ is not convincing in combination with BCG. Interleukin mediating therapies, such as ALT-803, are currently being studied. CONCLUSION: CPIs and other IM agents now offer an increasing opportunity for bladder-preserving strategies. Studies on different substances are ongoing and will yield new findings.

Nature videos for PTSD: protocol for a mixed-methods feasibility study.

Background: Given the prevalence of post-traumatic stress disorder (PTSD), particularly among military personnel, new treatment approaches are needed. One may be virtual relaxation interventions, especially 360-degree nature videos, since studies have demonstrated their relaxation effects for healthy participants. If these relaxation effects can be reproduced in patients with PTSD, they may offer a viable tool to reduce distress and hyperarousal. Objective: This research protocol describes a planned study that will examine the relaxation effects of 360-degree nature videos for patients with PTSD. It will also investigate whether these relaxation effects differ depending on the hardware immersion level (head-mounted display [HMD] vs. PC screen) in comparison to a control condition in which patients only listen to natural sounds and do not view a video. Finally, the effect of each intervention's dose duration (five vs. ten minutes) will be explored. Method: A counterbalanced, randomised, controlled, within-subject experiment will be conducted (sample size N = 36). Only soldiers aged 18 years or older with a primary diagnosis of PTSD will be included. Those with psychosis, substance dependence, a change in psychiatric medication within the last month, suicidal intent, and motion sickness will be excluded. All patients will experience the HMD, PC, and control conditions once for five or ten minutes. Self-reported relaxation measures will be collected before and after, and patients' skin conductance level, heart rate, and heart rate variability will be assessed during each condition. Semi-structured interviews will be conducted to examine the patients' experiences in detail. Conclusions: This feasibility study will provide initial evidence of whether viewing 360-degree nature videos via HMD or PC screen is relaxing for patients with PTSD and whether the effects are greater compared with the control condition. The study will also validate the dose duration and thereby informing a subsequent confirmatory interventional trial. Trial registration: DRKS00020277. HIGHLIGHTS: This randomised controlled feasibility study will examine whether 360-degree nature videos are a suitable relaxation intervention for military personnel with post-traumatic stress disorder.

Introducción: Dada la prevalencia del trastorno de estrés postraumático (TEPT), particularmente entre militares, se necesitan nuevos enfoques de tratamiento. Uno podría ser intervenciones de relajación virtual, especialmente videos de naturaleza de 360-grados, ya que los estudios han demostrado sus efectos de relajación para participantes sanos. Si estos efectos de relajación pueden reproducirse en pacientes con TEPT, podrían ofrecer una herramienta viable para reducir la angustia y la hiperalerta.Objetivo: Este protocolo de investigación describe un estudio planificado que examinará los efectos de relajación con videos de naturaleza de 360-grados, para pacientes con TEPT. También investigará de qué manera estos efectos de relajación difieren dependiendo del nivel de inmersión del hardware (pantalla montada en la cabeza [HMD] vs. pantalla de PC) en comparación con una condición de control en la que los pacientes solo escuchan los sonidos de la naturaleza y no ven un video. Finalmente, el efecto de la duración de la dosis de cada intervención (cinco vs diez minutos) será explorados.Método: Se llevará a cabo un experimento contrabalanceado, aleatorizado, controlado e intrasujeto (tamaño de muestra N = 36). Solo serán incluidos los soldados de 18 años o más con un diagnóstico primario de TEPT. Serán excluidos aquellos con psicosis, dependencia de sustancias, un cambio en la medicación psiquiátrica en el último mes y quienes presenten ideación suicida o cinetosis (mareo de movimiento). Todos los pacientes experimentarán las condiciones de HMD, PC y control una vez durante cinco o diez minutos. Las mediciones de relajación autoreportadas se recopilarán antes y después y el nivel de conductancia de la piel de los pacientes, la frecuencia cardíaca y la variabilidad de la frecuencia cardíaca se evaluarán durante cada condición. Se realizarán entrevistas semiestructuradas para examinar las experiencias de los pacientes en detalle.Conclusiones: Este estudio de factibilidad proporcionará evidencia inicial de si visualizar videos de naturaleza de 360-grados a través de HMD o la pantalla de la PC es relajante para los pacientes con TEPT, y si los efectos son mayores comparados con la condición de control. El estudio también validará la duración de la dosis y operacionalización de los puntos de termino, informando así un ensayo interventivo confirmatorio posterior.

Current Systemic Treatment Options in Metastatic Urothelial Carcinoma after Progression on Checkpoint Inhibition Therapy-A Systemic Review Combined with Single-Group Meta-Analysis of Three Studies Testing Enfortumab Vedotin.

BACKGROUND: In the first and second-line therapy of metastatic urothelial carcinoma (mUC), checkpoint inhibitors (CPI) such as Pembrolizumab and Atezolizumab have been widely implemented. Little is currently known about what therapeutic options are effective after therapy with CPI. This article presents a systemic review of current treatment options in this setting. METHODS: From August 2020 to 15 April 2021, a literature search was performed through the PubMed/Medline. Subsequently, a single-group meta-analysis of three studies testing Enfortumab vedotin (EV) was conducted. RESULTS: Five therapy regimens tested in the post-CPI setting with adequate data were identified: Chemotherapy (CT), Ramucirumab plus Docetaxel, Erdafitinib (Erd), EV, and Sacituzumab govitecan (SG). In n = 74 + 125 + 288 patients, the single-group meta-analysis showed an objective response rate of 42.1% for EV compared to 17.9% for CT in a similar setting. EV was also ahead in progression free survival (5.9 months with EV vs. 3.7 months with CT) and overall survival (12.8 months with EV vs. 9.0 months with CT). CONCLUSION: Most data are currently available for EV. Further research is needed on the question of which patients' subcollectives particularly benefit from which therapeutic approach.

Defining Spatial Relationships Between Spinal Cord Axons and Blood Vessels in Hydrogel Scaffolds.

Positively charged oligo(poly(ethylene glycol) fumarate) (OPF+) hydrogel scaffolds, implanted into a complete transection spinal cord injury (SCI), facilitate a permissive regenerative environment and provide a platform for controlled observation of repair mechanisms. Axonal regeneration after SCI is critically dependent upon nutrients and oxygen from a newly formed blood supply. Our objective was to investigate fundamental characteristics of revascularization in association with the ingrowth of axons into hydrogel scaffolds, thereby defining spatial relationships between axons and the neovasculature. A novel combination of stereologic estimates and precision image analysis techniques quantitate neurovascular regeneration in rats. Multichannel hydrogel scaffolds containing Matrigel-only (MG), Schwann cells (SCs), or SCs with rapamycin-eluting poly(lactic co-glycolic acid) microspheres (RAPA) were implanted for 6 weeks following complete spinal cord transection. Image analysis of 72 scaffold channels identified a total of 2494 myelinated and 4173 unmyelinated axons at 10 µm circumferential intervals centered around 708 individual blood vessel profiles. Blood vessel number, density, volume, diameter, intervessel distances, total vessel surface and cross-sectional areas, and radial diffusion distances were compared. Axon number and density, blood vessel surface area, and vessel cross-sectional areas in the SC group exceeded that in the MG and RAPA groups. Individual axons were concentrated within a concentric radius of 200-250 µm from blood vessel walls, in Gaussian distributions, which identified a peak axonal number (Mean Peak Amplitude) corresponding to defined distances (Mean Peak Distance) from each vessel, the highest concentrations of axons were relatively excluded from a 25-30 µm zone immediately adjacent to the vessel, and from vessel distances >150 µm. Higher axonal densities correlated with smaller vessel cross-sectional areas. A statistical spatial algorithm was used to generate cumulative distribution F- and G-functions of axonal distribution in the reference channel space. Axons located around blood vessels were definitively organized as clusters and were not randomly distributed. A scoring system stratifies 5 direct measurements and 12 derivative parameters influencing regeneration outcomes. By providing methods to quantify the axonal-vessel relationships, these results may refine spinal cord tissue engineering strategies to optimize the regeneration of complete neurovascular bundles in their relevant spatial relationships after SCI. Impact statement Vascular disruption and impaired neovascularization contribute critically to the poor regenerative capacity of the spinal cord after injury. In this study, hydrogel scaffolds provide a detailed model system to investigate the regeneration of spinal cord axons as they directly associate with individual blood vessels, using novel methods to define their spatial relationships and the physiologic implications of that organization. These results refine future tissue engineering strategies for spinal cord repair to optimize the re-development of complete neurovascular bundles in their relevant spatial architectures.

Psychopathology and Quality of Life in Traumatized or Victimized Underage Individuals as Factors for Forensic Multilevel Assessment-A Pilot Investigation.

Background: Psychological sequels to criminal violence can be long lasting and severe. They are in many countries not sufficiently considered in court cases as an important circumstance that could be used to assess the severity of the crime, also guiding redress, compensation, and rehabilitation of the victim, and-in children-child custody considerations. So far, the focus of forensic assessment has often been limited to diagnostic categories, especially "posttraumatic stress disorder" (PTSD), a diagnosis that presently is subjected to rapidly changing definitions both in and between diagnostic systems. Other indicators such as quality of life (QoL) might be of equal importance as compared to clinical or research diagnostic categories to understand and evaluate the impact of a crime and the amount of help needed and, in the legal context, redress to be asked. Symptoms might differ depending on the crime encountered. Objective and Methods: QoL and general symptom patterns including a PTSD diagnosis were assessed in a group of 10- to 17-year-old minors with (n = 33) and without (n = 49) PTSD diagnosis who all had experienced sexual abuse, physical abuse, death of a parent, or their parents' divorce, using standardized diagnostic instruments. Results: PTSD patients reported a significantly lower QoL than non-PTSD controls. Reported symptom patterns with potential impact on life, such as intrusive thoughts, differed between the victims of different crime types, with the highest rates of both intrusive symptoms and combined symptom profile in victims of sexual abuse. Data indicate that the changes between older and present criteria and between DSM and recently published ICD 11 might help identify different groups and symptom profiles. Conclusion: Specific trauma-related symptom profiles integrating the type of crime encountered and its individual impact on QoL may help improve future forensic assessment and guide compensation and rehabilitation plans. Carefully designed studies are now needed to further explore the use and forensic usability of complex indicators and the impact of violence in different forensic settings.