The effectiveness of adjustable trans-obturator male system (ATOMS) in radiated patients is reduced: A propensity score-matched analysis.

Objectives: This study aimed to compare the effectiveness and safety of the adjustable trans-obturator male system (ATOMS®) to treat post-prostatectomy incontinence (PPI) in radiated patients compared with non-radiated patients, using propensity score-matching analysis to enhance the validity of the comparison. Patients and methods: Consecutive men with PPI treated with silicone-covered scrotal port ATOMS (A.M.I., Feldkirch, Austria) in nine different institutions between 2016 and 2022 were included. Preoperative assessment evaluated 24-h pad usage, urethroscopy and urodynamics, if indicated. Propensity score-matching analysis was based on age, length of follow-up, previous PPI treatment, previous bladder neck stricture, androgen deprivation and pad usage. The primary endpoint was dry rate, defined as no pads post-operatively with a security pad allowed. The secondary endpoints were complications, device removal and self-perceived satisfaction with the Patient Global Impression of Improvement (PGI-I) scale. Results: Of the 710 included patients, 342 were matched, and the study groups were balanced for the baseline matched variables. The mean baseline 24-h pad was 4.8 in both groups (p = 0.48). The mean follow-up was 27.5 ± 18.6 months, which was also equivalent between groups (p = 0.36). The primary outcome was achieved in 73 (42.7%) radiated patients and in 115 (67.3%) non-radiated patients (p < 0.0001). The mean pad count at the last follow-up was 1.5 and 0.8, respectively (p < 0.0001). There was no significant difference in complications (p = 0.94), but surgical revision and device explant rates were higher (p = 0.03 and p = 0.01, respectively), and the proportion of patients highly satisfied (PGI-I = 1) was lower in the radiated group (p = 0.01). At sensitivity analysis, the study was found to be reasonably robust to hidden bias. Conclusion: ATOMS implantation significantly outperformed in patients without adjuvant radiation over radiated patients.

Long-Term Outcomes of the Altis® Single-Incision Sling: Up to 10 Years' Follow-up.

INTRODUCTION AND HYPOTHESIS: Single-incision slings (SIS) have emerged as a less invasive alternative to conventional slings for stress urinary incontinence (SUI) treatment. However, long-term efficacy and safety results remain uncertain owing to a lack of studies. MATERIAL AND METHODS: A retrospective review of 155 patients treated with Altis® for SUI between February 2012 and June 2017, held in 2022, as a continuation of a prospective study in which all patients (197) were reviewed for 2 years after surgery (1, 6, 12, and 24 months). Preoperative demographic data, comorbidities, and pressure-flow studies were also recorded. Continence status and satisfaction rates were assessed using the International Consultation on Incontinence Questionnaire-short form (ICIQ-SF) and the Patient Global Impression of Improvement (PGI-I) respectively. The assessment in the 2022 retrospective review was performed via a telephone survey. RESULTS: Mean follow-up time after surgery was 85.3 months (82.5-88.1). In 2022, complete continence was present in 75.4% of the patients. The presence of urinary urgency conditioned the ICIQ-SF score (10.9 vs 1.7 points, p < 0.01), with the ICIQ-SF = 0 in 84.5% of the patients with no associated urgency. Satisfaction assessed by the PGI-I was high, with 84.6% of the patients showing improvement. De novo urgency was present in 37,9% of the patients by 2022. Urinary tract infections were the most frequent complication (9.7%), with only 5 documented cases of mesh erosion. CONCLUSIONS: Altis® SIS is a safe and effective device for SUI treatment, with satisfaction rates comparable with those of the conventional slings. Persistence or development of urinary urgency influences the results.

Environmental Conditions as Determinants of Kidney Stone Formation.

Urolithiasis is a disease characterized by the presence of stones in the urinary tract, whether in the kidneys, ureters, or bladder. Its origin is multiple, and causes can be cited as hereditary, environmental, dietary, anatomical, metabolic, or infectious factors. A kidney stone is a biomaterial that originates inside the urinary tract, following the principles of crystalline growth, and in most cases, it cannot be eliminated naturally. In this work, 40 calculi from the Don Benito, Badajoz University Hospital are studied and compared with those collected in Madrid to establish differences between both populations with the same pathology and located in very different geographical areas. Analysis by cathodoluminescence offers information on the low crystallinity of the phases and their hydration states, as well as the importance of the bonds with the Ca cation in all of the structures, which, in turn, is related to environmental and social factors of different population groups such as a high intake of proteins, medications, bacterial factors, or possible contamination with greenhouse gases, among other factors.

Results of Adjustable Trans-Obturator Male System in Patients with Prostate Cancer Treated with Prostatectomy and Radiotherapy: A Multicenter Study.

(1) Background: Treatment of male stress incontinence in patients with prostate cancer treated with radical prostatectomy and adjuvant pelvic radiation is a therapeutic challenge. The efficacy and safety of the adjustable trans-obturator male system (ATOMS) in these patients is not well established, despite the general belief that outcomes are worse than in patients without radiation. (2) Methods: Retrospective multicenter study evaluating patients treated with silicone-covered scrotal port (SSP) ATOMS implant after radical prostatectomy and radiotherapy in nine different institutions between 2016 and 2022. The primary endpoint was dry patient rate, defined as pad-test ≤ 20 mL/day. The secondary endpoints were complication rate (defined using Clavien-Dindo classification), device removal and self-perceived satisfaction using the Patient Global Impression of Improvement (PGI-I) scale. Wilcoxon rank-sum test, Fisher's exact test and logistic regression were performed using stepwise method with a 0.15 entry and 0.1 stay criteria. (3) Results: 223 patients fulfilled the criteria for inclusion and 12 (5.4%) received salvage prostatectomy after radiation and 27 (12.1%) previous devices for stress incontinence. After ATOMS adjustment, 95 patients (42.6%) were dry and 36 (16.1%) had complications of any grade (grade I, n = 20; grade II, n = 11; grade III, n = 5) during the first 3 months postoperatively. At a mean of 36 ± 21 months follow-up, the device was explanted in 26 (11.7%) patients. Regarding self-perceived satisfaction with the implant, 105 of 125 patients (84%) considered themselves satisfied (PGI-I 1 to 3). In the univariate analysis, dryness was associated to younger age (p = 0.06), primary prostatectomy (p = 0.08), no previous incontinence surgery (p = 0.02), absence of overactive bladder symptoms (p = 0.04), absence of bladder neck stricture (p = 0.001), no need of surgical revision (p = 0.008) and lower baseline incontinence severity (p = 0.0003). Multivariate analysis identified absence of surgical revision (p = 0.018), absence of bladder neck stricture (p = 0.05), primary prostatectomy (p = 0.07) and lower baseline incontinence severity (p < 0.0001) were independent predictors of dryness. A logistic regression model was proposed and internally validated. (4) Conclusions: ATOMS is an efficacious and safe alternative to treat male incontinence after radical prostatectomy and adjuvant radiotherapy. Factors predictive of dryness are identified in this complex scenario to allow for better patient selection.

Is Extracorporeal Shock Wave Lithotripsy a Treatment Option for Renal Colic?

BACKGROUND: Renal colic is characterized by sharp, intense flank pain. Nonsteroidal anti-inflammatory drugs are the treatment of choice, although extracorporeal shock wave lithotripsy (SWL) is a noninvasive alternative for pain management. The objective of our study is to present results obtained using rapid SWL to treat renal colic in our center. METHODS: We analyzed 214 patients undergoing rapid shockwave extracorporeal lithotripsy between October 2014 and June 2018: 69.63% were male, and 30.37% female, with a mean age of 47.35 years (range, 16-84). The average stone size was 6.71 mm (3-16). Stone locations were as follows: The pelviureteric junction (PUJ) (10.75%), proximal ureter (45.79%), midureter (24.77%), and distal ureter (18.69%). RESULTS: Pain relief was achieved in 81.31% of the patients. The rates of successful pain control according to stone location were 65.22% when the stone was located in the PUJ, 79.59% in the proximal ureter, 88.68% in the midureter, and 85.00% in the distal ureter. Complete or partial stone resolution was achieved 4 weeks postoperatively in 78.50% of cases (64.95% and 13.55%, respectively). According to the stone location, the overall rate of resolution (complete + partial) was 90.00% for distal ureteral stones, 86.80% in the midureter, 73.47% in the proximal ureter, and 60.86% in the PUJ. 44 patients (20.56%) demonstrated complications. The most common complications were persistent pain, acute renal failure and fever. CONCLUSIONS: Immediate SWL was found to be a safe and effective treatment option for pain related to renal colic in 81% of the patients studied.

Stem Cell Therapy for Erectile Dysfunction: A Step towards a Future Treatment.

Background: The improvement of absent or partial response in the medical treatment of erectile dysfunction (ED) has led to the development of minimally invasive new treatment modalities in the field of regenerative medicine. Methods: A literature review on stem cell therapy for the treatment of ED was performed. We searched for the terms "erectile dysfunction" and "stem cell therapy" in PubMed and Clinicaltrials.gov. Literature searching was conducted in English and included articles from 2010 to 2022. Results: New treatment modalities for ED involving stem cell therapy are not only conceived with a curative intent but also aim to avoid unnecessary adverse effects. Several sources of stem cells have been described, each with unique characteristics and potential applications, and different delivery methods have been explored. A limited number of interventional studies over the past recent years have provided evidence of a safety profile in their use and promising results for the treatment of ED, although there are not enough studies to generate an appropriate protocol, dose or cell lineage, or to determine a mechanism of action. Conclusions: Stem cell therapy is a novel treatment for ED with potential future applications. However, most urological societies agree that further research is required to conclusively prove its potential benefit.

Value of Music and Nitrous Oxide for Pain Control during Extracorporeal Shock Wave Lithotripsy (ESWL).

OBJECTIVES: To compare the efficacy of 4 different analgesic regimens that include music and nitrous oxide during the treatment of renal lithiasis with ambulatory extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A single-centre, longitudinal, prospective, randomized, open and parallel group study was conducted. Patients with renal lithiasis were included and were randomized to Group A (basal analgesia: midazolam (1 mg), fentanyl (0.05 mg) and dexketoprofen (50 mg)), Group B (basal analgesia and nitrous oxide), Group C (basal analgesia and music) and Group D (basal analgesia, nitrous oxide and music). For the measurement of pain, a visual analogue scale ranging from 0 (no pain) to 100 (maximum pain imaginable) was used. Patient satisfaction was assessed using a Likert questionnaire. The epidemiological data of the patients in terms of lithiasis, previous clinical and ESWL sessions, and pain measured with the VAS before, during (maximum) at the end of the session and at discharge were recorded. Data on complications were also collected, as was the patients' subjective evaluation of the treatment and their satisfaction. The ESWL procedure was performed with a Storz Modulith SLX-F2® lithotripter. A maximum of 4000 waves were applied at a frequency of 1.5 Hz. RESULTS: Eighty patients were included (20 per group). None of the analgesia guidelines proved to be superior to the others for pain control during the ESWL session. Patients younger than 50 years had significantly higher values for the maximum VAS. Only 13.75% of patients required rescue analgesia. A total of 77.5% described their experience as good, very good or excellent, regardless of the assigned group. CONCLUSIONS: The addition of nitrous oxide and/or music did not result in a statistically significant improvement over the basal analgesia regimen of midazolam, fentanyl and dexketoprofen; however, the degree of patient satisfaction was very high.

Cross Talk between α7 and α3ß4 Nicotinic Receptors Prevents Their Desensitization in Human Chromaffin Cells.

The physical interaction and functional cross talk among the different subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) expressed in the various tissues is unknown. Here, we have investigated this issue between the only two nAChRs subtypes expressed, the α7 and α3ß4 subtypes, in a human native neuroendocrine cell (the chromaffin cell) using electrophysiological patch-clamp, fluorescence, and Förster resonance energy transfer (FRET) techniques. Our data show that α7 and α3ß4 receptor subtypes require their mutual and maximal efficacy of activation to increase their expression, to avoid their desensitization, and therefore, to increase their activity. In this way, after repetitive stimulation with acetylcholine (ACh), α7 and α3ß4 receptor subtypes do not desensitize, but they do with choline. The nicotinic current increase associated with the α3ß4 subtype is dependent on Ca2+ In addition, both receptor subtypes physically interact. Interaction and expression of both subtypes are reversibly reduced by tyrosine and serine/threonine phosphatases inhibition, not by Ca2+ In addition, expression is greater in human chromaffin cells from men compared to women, but FRET efficiency is not affected. Together, our findings indicate that human α7 and α3ß4 subtypes mutually modulate their expression and activity, providing a promising line of research to pharmacologically regulate their activity.SIGNIFICANCE STATEMENT Desensitization of nicotinic receptors is accepted to occur with repetitive agonist stimulation. However, here we show that human native α3ß4 and α7 nicotinic acetylcholine receptor (nAChR) subtypes do not desensitize, and instead, increase their activity when they are activated by the physiological agonist acetylcholine (ACh). An indispensable requirement is the activation of the other receptor subtype with maximal efficacy, and the presence of Ca2+ to cooperate in the case of the α3ß4 current increase. Because choline is an α3ß4 partial agonist, it will act as a limiting factor of nicotinic currents enhancement in the absence of ACh, but in its presence, it will further potentiate α7 currents.

[Renal harvest. State of the art.] / Extracción renal. Situación actual.

Kidney transplantation (KT) is the best treatment for end-stage renal disease. Despite Spain isone of the leading countries in donation, the need for transplantable organs exceeds the available supply. Graft survival depends on the quality of the organ, the damage it suffers during the donation and transplantation process, as well as the risk of rejection. Among the factors that must be controlled and minimized are the ischemia-reperfusion injuries that occurs in the moments surrounding the death of the donor, the procurement and the preservation of the organ until kidney transplantation. Static cold storage is the traditional method of preservation of the organ until the moment of implantation, since it is a technique with wide availability and low cost. The use of perfusion machines in DCD and expanded criteria has shown better short-term results (primary failur delayed on set of function) without affecting recipient orgraft survival. The objective of our article is to review the current situationand the resources available to increase the pool of transplantable organs and their quality. We conducted a systematic review on kidney extraction, donor management, preservation methods and techniques to optimize cadaveric donor kidney donation.

El trasplante renal (TR) es el mejor tratamiento para la enfermedad renal crónica terminal. En España no se dispone de suficientes órganos para suplirla demanda de pacientes en lista de espera a pesar deser uno de los países líderes en donación. La supervivencia del injerto depende de la calidad delórgano, el daño que sufre durante el proceso de donacióny trasplante, así como de la posibilidad de que seproduzca rechazo. Entre los factores que debemos minimizar y optimizar se encuentran las lesiones inducidas por los mecanismos de isquemia-reperfusión, en los momentos que rodean la muerte del donante, la extracción y la preservación del órgano hasta su trasplante.Tradicionalmente la preservación del órgano hasta elmomento del implante se ha llevado a cabo mediante la conservación en frío, ya que es una técnica con amplia disponibilidad y bajo coste. El uso de máquinas de perfusiónen donaciones en asistolia y criterio expandido,ha demostrado mejores resultados a corto plazo (fallo primario, inicio retrasado de función) sin afectar a la supervivencia del receptor o del injerto. El objetivo de este trabajo es revisar la situación actual,así como los recursos disponibles para aumentar el poolde órganos trasplantables y la calidad de estos. Hemos realizado una revisión sobre la extracción renal, manejo del donante, métodos y técnicas de preservación para optimizar la donación renal de donante cadáver.

Adjustable Transobturator Male System (ATOMS) Infection: Causative Organisms and Clinical Profile.

OBJECTIVE: To evaluate the clinical profile and the organisms producing adjustable transobturator male system (ATOMS) infection in a contemporary series. METHODS: Multicenter retrospective study evaluating patients undergoing ATOMS explant for clinical signs of infection from a series of 902 patients treated in 9 academic institutions. Clinical and microbiological data were evaluated. RESULTS: Infection presented in 24 patients (2.7%). The median age was 73 ± 7yrs and the median interval from ATOMS implantation to explant 11 ± 26.5mo. Infection was diagnosed within 3-months after surgery in 7(29.2%). Scrotal port erosion was present in 6 cases (25%) and systemic symptoms of parenchymatous testicular infection in 2(8.3%). The culture of the periprosthetic fluid was positive in 20(83.3%): 12(50%) Gram-negative bacteria, 9(37.5%) Gram-positive cocci and 1(4.2%) yeast. The most frequent isolates were Enterococcus and Proteus sp. (16.7% each), followed by Pseudomona sp. and S. epidermidis (12.5% each). Methicillin resistant S. aureus was detected only in 1 case (4.2%). Despite the infection 17 patients (70.8%) were satisfied with the implant and 18(75%) received a second device (11 repeated ATOMS and 7 AUS) at a median 9.7 ± 12.6mo after explant. Limitations include retrospective design and lack of microbiological cultures in ATOMS explanted for non-infective cause. CONCLUSION: Infection of a prosthetic device is a disturbing complication. A proportion of patients with ATOMS infection is associated to scrotal port erosion and/or parenchymatous urinary tract infection. Enterococcus and Proteus sp. are the most common organisms producing ATOMS infection and this could have implications for the selection of the most appropriate surgical prophylaxis.

Comparative study between patients undergoing laparoscopic colposacropexy with and without prior surgery for the treatment of apical prolapse. / Estudio comparativo entre pacientes sometidos a colposacropexia laparoscópica con y sin cirugía previa para el tratamiento del prolapso apical.

INTRODUCTION: Colposacropexy is the treatment of choice for apical prolapse. Studies comparing this technique as primary surgery for pelvic organprolapse (POP), with its success in recurrent POPs after surgery, are scarce. MATERIALS AND METHODS: Retrospective analysis of a series of patients diagnosed with POP who underwent laparoscopic colposacropexy, comparing a group without previous prolapse surgery with another group that has recurred after previous surgery (with or without mesh). Our objective was to analyze the differences regarding surgical time (skin to skin), intraoperative complications, mean stay, resolution of symptoms and recurrence. As preoperative data, we compared: age, body mass index (BMI), parity, previous hysterectomy, physical examination, symptoms, and flowmetry; and as peri/postoperative data: follow-up, intervention duration, intra and postoperative complications, mean stay, physical examination (Baden-Walker classification), symptom resolution and flowmetry. RESULTS: Twenty-three patients have been operated on in 12 months. Nine (39.1%) were recurrent POPs after previous surgery, 6 (66.7%) of them with some type of mesh. Follow-up (mean months): 6.44 ± 4.19 (previous cx) vs. 4.79 ± 4.00. Both groups were comparable with respect to preoperative variables. Previously operated patients had greater dyspareunia (p<0.05). We did not find differences in the rest of symptoms between both groups. There were no differences in the duration of the intervention, mean stay, or regarding intraoperative complications (p>0.05) between both groups. Sensation of vaginal lump, urge incontinence and dyspareunia resolved in all patients. Flowmetry improved in both groups (p>0.05). CONCLUSIONS: Laparoscopic colposacropexy is an effective and safe technique to correct POP after previous surgery, with or without mesh.

INTRODUCCIÓN: La colposacropexia es el tratamiento de elección para el prolapso apical. Los estudios que comparan esta técnica como cirugía primaria para el prolapso de órganos pélvicos (POP), consu éxito en los POP recidivados tras cirugía son escasos.MATERIAL Y MÉTODOS: Análisis retrospectivo de una serie de pacientes con diagnóstico de POP sometidas a colposacropexia laparoscópica, comparando un grupo sin cirugía previa para el prolapso, con otro que ha recidivado tras cirugía previa (con o sin malla). Nuestro objetivo fue analizar las diferencias respecto al tiempo quirúrgico (de piel a piel), complicaciones intraoperatorias, estancia media, resolución de los síntomas y recidiva. Como datos preoperatorios se compararon: edad, índice de masa corporal (IMC), paridad, histerectomía previa, exploración física, sintomatología y flujometría; y como datos peri/postoperatorios: seguimiento, duración intervención, complicaciones intra y postoperatorias, estancia media, exploración física (clasificación Baden-Walker), resolución síntomas y flujometría.RESULTADOS: Han sido intervenidas 23 pacientes en12 meses. Nueve (39,1%) eran POP recidivados tras cirugía previa, 6 (66,7%) de ellas con algún tipo de malla. Seguimiento (media meses): 6,44 ± 4,19 (cx previa) vs 4,79 ± 4,00. Ambos grupos fueron comparables respecto a las variables preoperatorias. Las pacientes intervenidas previamente presentaban mayor dispareunia (p <0,05). No encontramos diferencias en el resto de síntomas entre ambos grupos. No hubo diferencias en duración de la intervención, estancia media, ni respecto a las complicaciones intraoperatorias (p>0,05) entre ambos grupos. La sensación de bultovaginal, la urge-incontinencia y la dispareunia se resolvieron en todas las pacientes. La flujometría mejoró en ambos grupos (p>0,05).CONCLUSIONES: La colposacropexia laparoscópica es una técnica eficaz y segura para la corrección del POP tras cirugía previa, con o sin malla.

Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine.

Cardiovascular side effects of varenicline and a case report of a hypertensive crisis in a varenicline-prescribed patient with pheochromocytoma have been reported. The goal of the present study was to determine whether such side effects might derive, in part, from increased exocytosis of secretory vesicles and subsequent catecholamine release triggered by varenicline in human chromaffin cells of the adrenal gland. In this study, we performed electrophysiological plasma membrane capacitance and carbon fiber amperometry experiments to evaluate the effect of varenicline on exocytosis and catecholamine release, respectively, at concentrations reached during varenicline therapy (100 nM). Experiments were conducted in the absence or presence of nicotine, at plasma concentrations achieved right after smoking (250 nM) or steady-state concentrations (110 nM), in chromaffin cells of the adrenal gland obtained from human organ donors. Cells were stimulated with short pulses (10 ms) of acetylcholine (ACh; 300 µM) applied at 0.2 Hz, in order to closer mimic the physiological situation at the splanchnic nerve-chromaffin cell synapse. In addition, rat chromaffin cells were used to compare the effects obtained in cells from a more readily available species. Varenicline increased the exocytosis of secretory vesicles in human and rat chromaffin cells in the presence of nicotine, effects that were not due to an increase of plasma membrane capacitance or currents triggered by the nicotinic agonists alone. These results should be considered in nicotine addiction therapies when varenicline is used.

Artificial urinary sphincter or a second adjustable transobturator male system offer equivalent outcomes in patients whom required revision on the initial ATOMS device: An international multi-institutional experience.

AIM: To evaluate treatment options after surgical revision of adjustable transobturator male system (ATOMS) and the results of further incontinence implantation. MATERIALS AND METHODS: A retrospective multicenter study evaluating patients with surgical revision of ATOMS in academic institutions. Causes and factors affecting revision-free interval were studied and also the frequency of device explant and placement of second ATOMS or artificial urinary sphincter (AUS) at surgeon discretion. Operative results, complications (Clavien-Dindo), and efficacy (postoperative pad-test, pad-count, patient satisfaction, and patient global impression of improvement [PGI-I scale]) of each treatment option were compared. RESULTS: Seventy-eight out of 902 patients (8.65%) with ATOMS underwent surgical revision at 4.1 ± 2.4 years mean follow-up and 75 (8.3%) were explanted. The main causes for revision included persistence of incontinence (35.9%) and scrotal port erosion (34.6%). Independent risk factors of the shortened revision-free interval were previous anti-incontinence surgery (HR, 1.83; 95% CI, 1.06-3.16; p = 0.007) and port erosion (HR, 1.83; 95% CI, 1.06-3.16; p = 0.0027). Fifty-eight (6.4%) received a second implant: 31 repeated ATOMS and 27 AUS. Operative time was longer for AUS (p = .003). The visual analog scale of pain at hospital discharge (p = 0.837) and postoperative complications (p = 0.154) were equivalent. The predominant cuff size for AUS was 4.5 cm (59.3%). Mean follow-up after the second implant was 29.1 ± 25.8 months. Postoperative efficacy of secondary treatment results favored ATOMS based on pad-test (p = 0.016), pad-count (p = 0.029), patient satisfaction (p = 0.04), and PGI-I (p = 0.025). CONCLUSIONS: ATOMS surgical revision due to different reasons generally leads to device explant. Rescue treatment is possible with ATOMS or AUS. No difference in postoperative complications was detected between secondary devices, but efficacy favors repeating ATOMS implantation.

Urinary Cyclophilin A as Marker of Tubular Cell Death and Kidney Injury.

Background: Despite the term acute kidney injury (AKI), clinical biomarkers for AKI reflect function rather than injury and independent markers of injury are needed. Tubular cell death, including necroptotic cell death, is a key feature of AKI. Cyclophilin A (CypA) is an intracellular protein that has been reported to be released during necroptosis. We have now explored CypA as a potential marker for kidney injury in cultured tubular cells and in clinical settings of ischemia-reperfusion injury (IRI), characterized by limitations of current diagnostic criteria for AKI. Methods: CypA was analyzed in cultured human and murine proximal tubular epithelial cells exposed to chemical hypoxia, hypoxia/reoxygenation (H/R) or other cell death (apoptosis, necroptosis, ferroptosis) inducers. Urinary levels of CypA (uCypA) were analyzed in patients after nephron sparing surgery (NSS) in which the contralateral kidney is not disturbed and kidney grafts with initial function. Results: Intracellular CypA remained unchanged while supernatant CypA increased in parallel to cell death induction. uCypA levels were higher in NSS patients with renal artery clamping (that is, with NSS-IRI) than in no clamping (NSS-no IRI), and in kidney transplantation (KT) recipients (KT-IRI) even in the presence of preserved or improving kidney function, while this was not the case for urinary Neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, higher uCypA levels in NSS patients were associated with longer surgery duration and the incidence of AKI increased from 10% when using serum creatinine (sCr) or urinary output criteria to 36% when using high uCypA levels in NNS clamping patients. Conclusions: CypA is released by kidney tubular cells during different forms of cell death, and uCypA increased during IRI-induced clinical kidney injury independently from kidney function parameters. Thus, uCypA is a potential biomarker of kidney injury, which is independent from decreased kidney function.

ATOMS (Adjustable Transobturator Male System) Is an Effective and Safe Second-Line Treatment Option for Recurrent Urinary Incontinence after Implantation of an AdVance/AdVance XP Fixed Male Sling? A Multicenter Cohort Analysis.

(1) Background: This study examined outcomes of second-line ATOMS implantation after failure of the fixed male sling (FMS) AdVance/AdVance XP. (2) Methods: A retrospective multicenter cohort analysis was carried out in men implanted with an ATOMS between 2011 and 2020 after failure of an AdVance/AdVance XP. Success was assessed on the basis of objective (dryness, 0-1 pad/24 h or >20 g/24 h pad test) and subjective results (PGI-I). We performed the Wilcoxon rank sum test, Fisher's exact test, logistic regression, and multivariate analysis. (3) Results: The study included 88 patients from 9 centers with a mean age of 71.3 years. No Clavien-Dindo > II complications occurred within the first 3 months after ATOMS implantation. A total of 10 cases (9%) required revision in the ensuing clinical course. After a mean follow-up of 42.5 months, 76.1% achieved social continence, and 56.8% used no pads at all. Mean urine leakage/24 h dropped from 422 g (3.9 pads) to 38 g (0.69 pads) and the mean ICIQ-SF decreased from 16.25 to 5.3 (p < 0.0001). PROMs (patient-reported outcome measures) showed improvement in 98.9% of cases, and 63.6% gave a "very much better" PGI-I rating. Multivariate analysis identified a lower probability of achieving maximum satisfaction for the following factors: the AdVance XP as first-line therapy (OR 0.35), a lower ICIQ-SF question 1 (OR 0.26), status post-irradiation (OR 0.14), and more severe pain prior to ATOMS implantation (OR 0.51). (4) Conclusions: Implantation of an ATOMS is an effective and safe second-line treatment option for recurrent urinary incontinence after implantation of an AdVance/AdVance XP sling. High patient satisfaction was demonstrated in a long-term follow-up.

Positive/retained SDHB immunostaining in renal cell carcinomas associated to germline SDHB-deficiency: case report.

BACKGROUND: According to WHO, succinate dehydrogenase (SDH)-deficient renal cell carcinoma is characterized by negative immunostaining for SDHB, which remains positive in non-tumor tissue despite germline mutations in the SDHB gene. We now report a patient with a SDHB mutation, c.166_170del (p.Pro56Tyrfs*5) who developed renal cell carcinomas with characteristic morphological features of SDH-deficient renal cell carcinoma but had positive SDHB immunostaining. CASE PRESENTATION: Within a 6-year period, the patient developed two different renal cell carcinomas, which had characteristic morphological features of SDH-deficient renal cell carcinoma (uniform cells characteristically displaying eosinophilic granular material intermixed with fewer cells exhibiting clear intracytoplasmic inclusions and bland centered nuclei) but displayed immunohistochemistry for SDHB with a cytoplasmic granular positivity (mitochondrial pattern) in tumor cells. For the second case, this was initially interpreted as positive by IHC, but on review some subtle differences were identified. CONCLUSIONS: SDHB immunostaining may be positive in renal cell carcinoma associated to germline SDHB deficiency which have other typical morphological features. Immunohistochemistry interpretation may be complex.

PGC-1α deficiency causes spontaneous kidney inflammation and increases the severity of nephrotoxic AKI.

PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α, PPARGC1A) regulates the expression of genes involved in energy homeostasis and mitochondrial biogenesis. Here we identify inactivation of the transcriptional regulator PGC-1α as a landmark for experimental nephrotoxic acute kidney injury (AKI) and describe the in vivo consequences of PGC-1α deficiency over inflammation and cell death in kidney injury. Kidney transcriptomic analyses of WT mice with folic acid-induced AKI revealed 1398 up- and 1627 downregulated genes. Upstream transcriptional regulator analyses pointed to PGC-1α as the transcription factor potentially driving the observed expression changes with the highest reduction in activity. Reduced PGC-1α expression was shared by human kidney injury. Ppargc1a-/- mice had spontaneous subclinical kidney injury characterized by tubulointerstitial inflammation and increased Ngal expression. Upon AKI, Ppargc1a-/- mice had lower survival and more severe loss of renal function, tubular injury, and reduction in expression of mitochondrial PGC-1α-dependent genes in the kidney, and an earlier decrease in mitochondrial mass than WT mice. Additionally, surviving Ppargc1a-/- mice showed higher rates of tubular cell death, compensatory proliferation, expression of proinflammatory cytokines, NF-κB activation, and interstitial inflammatory cell infiltration. Specifically, Ppargc1a-/- mice displayed increased M1 and decreased M2 responses and expression of the anti-inflammatory cytokine IL-10. In cultured renal tubular cells, PGC-1α targeting promoted spontaneous cell death and proinflammatory responses. In conclusion, PGC-1α inactivation is a key driver of the gene expression response in nephrotoxic AKI and PGC-1α deficiency promotes a spontaneous inflammatory kidney response that is magnified during AKI. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Prospective Observational Cohort Study of the Efficacy of Bacterial Immune Prophylaxis in the Prevention of Uncomplicated, Recurrent Urinary Tract Infections.

OBJECTIVE: To investigate the long-term prophylactic effect of a vaccine on lower urinary tract infections (UTI) of bacterial and the impact of the intensity of the symptoms on the quality of life (QoL). METHODS: Adult female could be enrolled in this study if they had acute UTI at the enrolment visit and bacterial microbiological count of ≥103 CFU/mL of Escherichia coli. RESULTS: A total of 21 patients were included. Fifteen days after the administration of a vaccine for 3 months, the number of infections dropped almost to zero. Significant differences were observed in the QoL score (p < 0.05). The safety profile was good. CONCLUSIONS: In patients diagnosed with recurrent UTI and treated for 3 months with the vaccine the number of UTI episodes fell very quickly (15 days), and patients remained free of episodes and improved their QoL significantly for 1 year. These results suggest that bacterial vaccines are a possible effective alternative in the prevention of recurrent UTI.

Validation of a Novel, Sensitive, and Specific Urine-Based Test for Recurrence Surveillance of Patients With Non-Muscle-Invasive Bladder Cancer in a Comprehensive Multicenter Study.

Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70-75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3 hotspot mutations are the most frequent somatic alterations in BC and constitute the most reliable biomarkers for BC. Based on these, we developed an ultra-sensitive, urine-based assay called Uromonitor®, capable of detecting trace amounts of TERT promoter (c.1-124C > T and c.1-146C > T) and FGFR3 (p.R248C and p.S249C) hotspot mutations, in tumor cells exfoliated to urine samples. Cells present in urine were concentrated by the filtration of urine through filters where tumor cells are trapped and stored until analysis, presenting long-term stability. Detection of the alterations was achieved through a custom-made, robust, and highly sensitive multiplex competitive allele-specific discrimination PCR allowing clear interpretation of results. In this study, we validate a test for NMIBC recurrence detection, using for technical validation a total of 331 urine samples and 41 formalin-fixed paraffin-embedded tissues of the primary tumor and recurrence lesions from a large cluster of urology centers. In the clinical validation, we used 185 samples to assess sensitivity/specificity in the detection of NMIBC recurrence vs. cystoscopy/cytology and in a smaller cohort its potential as a primary diagnostic tool for NMIBC. Our results show this test to be highly sensitive (73.5%) and specific (93.2%) in detecting recurrence of BC in patients under surveillance of NMIBC.

[Aggressive variants of castration resistant prostate cancer (CRPC): neuroendocrine prostate cancer.] / Variantes agresivas de cáncer de próstata resistente a la castracion (CPRC): cáncer de próstata neuroendocrino.

Castration resistant prostate cancer (CRPC) is characterized by an important molecular, pathological and clinical heterogeneity. Although most of them present androgen receptor (AR) signal dependence, there are independent phenotypes. Neuroendocrine prostate cancer (NEPC) is a rare histologic subtype with adverse prognosis due to late diagnosis, heterogeneous clinical features and lack of effective systemic treatments. Platinum based chemotherapy is the standard treatment, presenting short limited responses. There are pure forms or mixed with adenocarcinoma component. De novo diagnosis is unusual, being more frequent in advanced stages of prostate cancer, as a consequence of the inhibition of androgen receptor performed by various treatments. Thus, it could represent an aggressive evolution from carcinoma through a NEEpithelial transdifferentiation. Development of preclinical studies has permitted characterization of molecular and genomic alterations associated with this evolution and they may help to develop new therapeutic targets. Over the last years, there have been important advances in identification and characterization of clinical and pathological CRPC variants. NEPC is one of the most aggressive subtypes. A better knowledge of the disease biology is necessary to develop new treatments and biomarkers that help to manage this aggressive variant of PC.