Complicated Urinary Tract Research Articles

Design and Evaluation of Inorganic/Organic Hybrid Bio-composite for Site-Specific Oral Delivery of Darifenacin

Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development. An inorganic/organic bio-composite with gastric pH-resistant property was synthesized for the targeted oral delivery of Darifenacin to the lower gastrointestinal tract (GIT). This development was accomplished through co-precipitation of calcium carbonate in quince seed-based mucilage. The FTIR, XRD, DSC, and TGA results showed good drug-polymer compatibility, and the SEM images showed calcite formation in the quince hydrogel system. After 72 h, the drug release of 34% and 75% were observed in acidic (0.1N HCl) and 6.8 pH phosphate buffer, respectively. A restricted/less drug was permeated through gastric membrane (21.8%) as compared to permeation through intestinal membrane (65%.) The developed composite showed significant reduction in testosterone-induced prostatic hyperplasia (2.39 ± 0.12***) as compared to untreated diseased animal group. No sign of organ toxicity was observed against all the developed composites. In this study, we developed an inorganic–organic composite system that is highly biocompatible and effective for targeting the lower GIT, thereby avoiding the first-pass metabolism of darifenacin.Graphical

Challenging urological reconstruction in post-tuberculosis contracted bladder and renal complications: A rare case report

Genitourinary Tuberculosis (GUTB) represents a manifestation of extrapulmonary tuberculosis associated with significant urinary tract complications, such as contracted bladder and renal insufficiency. This report delineates a rare instance of GUTB culminating in considerable urological impairment, necessitating complex reconstructive procedures.

Initial Experience With Inpatient Hospital Care at Home for Urologic Disease.

In 2020, Mayo Clinic launched Advanced Care at Home (ACH), a hospital-at-home program that cares for high-acuity inpatients via remote monitoring and in-person care. Herein, we describe our initial experience utilizing ACH for patients with urologic problems. We identified ACH patients treated at Mayo Clinic Florida from July 2020 to August 2022. Records were reviewed to identify those with urologic problems, defined as genitourinary infections, urinary tract obstruction, bleeding, or complications following urologic surgery within 90 days of admission. Demographics, Charlson Comorbidity Index, ACH interventions, length of stay, and hospital readmission were assessed. We identified 563 ACH admissions involving 537 patients, of whom 51 (9%) had illnesses with urologic etiology and 3 (0.6%) were admitted for nonurologic postoperative complications following urologic surgery. Admitting diagnoses included pyelonephritis (n = 51, 91%) and epididymoorchitis (n = 2, 4%). Postoperative diagnoses included cellulitis (n = 1, 2%), congestive heart failure (n = 1, 2%), and diverticulitis (n = 1, 2%). Median Charlson Comorbidity Index of admitted patients was 4 (interquartile range: 3-6.8). Twenty-five patients (46%) underwent 38 urologic procedures within 90 days of admission. Interventions included IV antibiotics (n = 51, 91%), IV fluids (n = 12, 21%), IV antifungals (n = 2, 4%), and oral diuretic therapy (n = 1, 2%). Median length of stay was 3 days (interquartile range: 2-4), and 9 patients (16%) were readmitted within 30 days. A total of 216 inpatient hospital days were saved by utilizing ACH. ACH appeared to be a feasible alternative to brick-and-mortar inpatient care for patients with genitourinary infections requiring IV antimicrobials.

Contrast-enhanced US in Renal Transplant Complications: Overview and Imaging Features.

Renal transplant is the first-line treatment of end-stage renal disease. The increasing number of transplants performed every year has led to a larger population of transplant patients. Complications may arise during the perioperative and postoperative periods, and imaging plays a key role in this scenario. Contrast-enhanced US (CEUS) is a safe tool that adds additional value to US. Contrast agents are usually administered intravenously, but urinary tract anatomy and complications such as stenosis or leak can be studied using intracavitary administration of contrast agents. Assessment of the graft and iliac vessels with CEUS is particularly helpful in identifying vascular and parenchymal complications, such as arterial or venous thrombosis and stenosis, acute tubular injury, or cortical necrosis, which can lead to graft loss. Furthermore, infectious and malignant graft involvement can be accurately studied with CEUS, which can help in detection of renal abscesses and in the differentiation between benign and malignant disease. CEUS is also useful in interventional procedures, helping to guide percutaneous aspiration of collections with better delimitation of the graft boundaries and to guide renal graft biopsies by avoiding avascular areas. Potential postprocedural vascular complications, such as pseudoaneurysm, arteriovenous fistula, or active bleeding, are identified with CEUS. In addition, newer quantification tools such as CEUS perfusion are promising, but further studies are needed to approve its use for clinical purposes. ©RSNA, 2024 Supplemental material is available for this article.

Endoscopic combined intrarenal surgery versus percutaneuos nephrolithotomy for complex pediatric stone disease: A comparative analysis of efficacy and safety

INTRODUCTIONDecision-making for complex pediatric urinary system stone disease is still a challenge for pediatric urologists. The interest in supine percutaneous nephrolithotomy (PCNL) is increasing among centers to achieve high surgical success rates with less morbidity. Despite advanced retrograde intrarenal surgery armamentarium, percutaneous approaches remain the first-line surgical treatment modality for >2 cm and complex renal stones. There are no comparative studies yet in the literature for pediatric endoscopic combined intrarenal surgery (ECIRS) OBJECTIVEIn this study, we aimed to contribute to the literature by evaluating the safety and efficacy of ECIRS by comparing it with PCNL. STUDY DESIGNPatients under 18 years of age who underwent PCNL and ECIRS for urinary tract stone disease at our Pediatric Urology department between 2012 and 2024 were included. Preoperative (demographic characteristics, stone characteristics, biochemical parameters), perioperative (duration of surgery, number of accesses, lasing and fluoroscopy times, endoscopic and fluoroscopic stone-free rates) and postoperative (hospital stay, urinary tract infection, complication and radiological stone-free rates) parameters were retrospectively evaluated. RESULTSA total of 68 children [28 (41%) girls and 40 (59%) boys] aged 5 (0-17) years were included in the study. ECIRS was performed in 19 (28%), supine in 28 (41%) and prone PCNL in 21 (30%) patients. Age (p = 0.029), Guy's stone score (p<0.001), S.T.O.N.E. (p<0.001), and Seoul National University Renal Stone Complexity (S-ReSC) scores (p=0.001) for preoperative parameters were found to be higher in ECIRS group over both PCNL methods (Summary Table). However, Clinical Research Office of the Endourological Society (CROES) score was seen lower for ECIRS group patients compared to other groups (p=0.028).Surgery time (in favor of supine over prone PCNL), fluoroscopy time (in favor of ECIRS and Supine PCNL over Prone PCNL), preferred laser type (prone PCNL group was mostly performed with holmium laser, whereas other groups were balanced between Holmium and Thulium Fiber Laser) and exit strategy (the preferred exit strategy was DJ Stent in most of the ECIRS patients, whereas nephrostomy tube was used in some of the PCNL group) showed significant difference among the groups as perioperative parameters (p=0.042, <0.001, <0.001, <0.001, respectively). Surgery time was lower for supine PCNL compared to prone PCNL. For postoperative parameters, stone-free rates, complication rates and urinary tract infections were similar between the 3 groups, while a difference was detected in terms of length of hospital stay in favor of ECIRS over both supine and prone PCNL (p = 0.006). DISCUSSIONThe current trial suggests that stone-free and complication rates of ECIRS and supine PCNL were similar in the pediatric complex stone patients. Although, the stones in the ECIRS group we found to be more complex. Also, ECIRS was superior to PCNL in terms of fluoroscopy exposure and hospital stay. CONCLUSIONWith the widespread use of new generation ureteral access sheaths and flexible ureterorenoscopes, ECIRS may have an important role in treatment of complex pediatric kidney stones.

In vitro and in vivo activities of KSP-1007, a broad-spectrum inhibitor of serine- and metallo-β-lactamases, in combination with meropenem against carbapenem-resistant Gram-negative bacteria.

KSP-1007 is a novel bicyclic boronate-based broad-spectrum β-lactamase inhibitor and is being developed in combination with meropenem (MEM) for the treatment of infections caused by carbapenem-resistant Gram-negative bacteria, a global health concern, and here, we describe its characteristics. KSP-1007 exhibited low apparent inhibition constant (Ki app) values against all classes of β-lactamase, including imipenemase types and oxacillinase types from Acinetobacter baumannii. Against 207 Enterobacterales and 55 A. baumannii, including carbapenemase producers, KSP-1007 at fixed concentrations of 4, 8, and 16 µg/mL dose-dependently potentiated the in vitro activity of MEM in broth microdilution MIC testing. The MIC90 of MEM/KSP-1007 at 8 µg/mL against Enterobacterales was lower than those of MEM/vaborbactam, ceftazidime/avibactam, imipenem/relebactam, and colistin and similar to those of aztreonam/avibactam, cefiderocol, and tigecycline. The in vitro activity of MEM/KSP-1007 at ≥4 µg/mL against Enterobacterales harboring metallo-β-lactamase was superior to that of cefepime/taniborbactam. MEM/KSP-1007 showed excellent activity against Escherichia coli with PBP3 mutations and New Delhi metallo-β-lactamase compared to aztreonam/avibactam, cefepime/taniborbactam, and cefiderocol. MEM/KSP-1007 at 8 µg/mL showed greater efficacy against A. baumannii than these comparators except for cefiderocol, tigecycline, and colistin. A 2-fold reduction in MEM MIC against 96 Pseudomonas aeruginosa was observed in combination with KSP-1007. MEM/KSP-1007 demonstrated bactericidal activity against carbapenemase-producing Enterobacterales, A. baumannii, and P. aeruginosa based on minimum bactericidal concentration/MIC ratios of ≤4. KSP-1007 enhanced the in vivo activity of MEM against carbapenemase-producing Enterobacterales, A. baumannii, and P. aeruginosa in murine systemic, complicated urinary tract, and thigh infection models. Collectively, MEM/KSP-1007 has a good profile for treating carbapenem-resistant Gram-negative bacterial infections.

Radical prostatectomy versus radiotherapy as local therapy for primary tumors in patients with oligometastatic prostate cancer.

We compared radical prostatectomy (RP) and radiotherapy (RT) as local therapies for primary tumors and examined their associations with survival outcomes and urinary tract complications in patients with oligometastatic prostate cancer (omPC). We evaluated the data of 85 patients diagnosed with omPC who underwent local therapy for primary tumors between January 2008 and December 2018. Of the 85 patients, 31 underwent prostate RT, while 54 underwent RP. Oligometastatic disease was defined as the presence of fewer than five metastatic lesions without visceral metastasis. Urinary tract complications, progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated using the Kaplan-Meier method and Cox regression analyses. Patients treated with RT showed higher prostate-specific antigen levels. There was no significant difference in the 5-year PFS (52.5% vs. 37.9%, p=0.351), CSS (67.6% vs. 84.7%, p=0.473), or OS (63.6% vs. 73.8%, p=0.897) between the RT and RP groups. In the multivariate analyses, the type of local therapy was not associated with PFS (hazard ratio [HR]=1.334, p=0.356), CSS (HR=0.744, p=0.475), or OS (HR=0.953, p=0.897). Therefore, RP seems to be a possible treatment option for patients with omPC, exhibiting oncologic outcomes comparable to those with RT.

(212) Minimally Invasive Surgical Therapies for Benign Prostatic Hyperplasia in the Geriatric Population: A Systematic Review

Abstract Introduction Benign prostatic hyperplasia (BPH) is an extremely common disease in aging men and can lead to lower urinary tract symptoms (LUTS) and complications. While the initial management of BPH includes behavioral modifications and pharmacologic therapies, older patients have increased susceptibility to adverse events (AEs) and therefore have decreased compliance. Consequently, geriatric patients may benefit from minimally invasive surgical therapies (MISTs) as treatment alternatives for BPH. Currently, there is no systematic review describing MISTs outcomes in specifically older populations. Objective To evaluate the efficacy and safety profile of MISTs in geriatric patients with BPH. Methods PubMed/MEDLINE database was systematically searched for relevant articles in the English language through June 24, 2023. Studies that evaluated surgical and/or urinary outcomes of MISTs in geriatric patients (≥65 years of age) were deemed eligible. Studies were included if there was separate reporting for age subgroups ≥65 years, if mean age minus SD was ≥65 years, or if median age minus Q1 was ≥65 years. Studies with patients with catheter dependent urinary retention were not excluded. Results A total of 263 studies were screened, of which 22 (N=2,911 patients) met inclusion. Of the 22 studies, 3 evaluated PAE, 1 evaluated Rezum, 7 evaluated GreenLight, 4 evaluated HoLEP, 4 evaluated ThuLEP, 1 evaluated DiLEP, 1 evaluated Aquablation, and 1 evaluated both PAE + Rezum. The Rezum study and the PAE + Rezum study only included patients with an indwelling catheter at baseline. Follow-up ranged between 1 and 36 months (median 12 months). All the MISTs were performed inpatient and required hospitalization. Hospitalization times ranged between 0.9 and 7.6 days (median 3 days) and was the longest for DiLEP (median 7.6 days) and PAE (median 5.1 days) and the shortest for Rezum (median 1 day). Procedure time ranged between 4.8 and 148 minutes (median 70.6 minutes), with PAE having the longest time (median 102 minutes) and Rezum having the shortest time (median 6.4 minutes). When compared to baseline, PAE, GreenLight, HoLEP, ThuLEP, DiLEP, and Aquablation showed significant percent changes in international prostate symptom score (median -69.6%), quality of life (-72.7%), maximum urinary flow (113.1%), and postvoid residual (-80.1%) at a median of 12 months postoperatively. The studies assessing catheter independence in patients with chronic urinary retention reported a catheter-free rate of 100% for Rezum and 45.5% for PAE at 12 months postoperatively. Occurrence of AEs ranged between 0 and 67.5% (median 12.2%). AEs were lowest for HoLEP (median 4.6%) and Rezum (median 8.8%) and highest for PAE (33.1%) and Aquablation (34%). Reoperation rates across all MISTs ranged between 0 and 5% (median 1.5%) at a median of 12 months postoperatively. Conclusions Although all the MISTs reviewed in this study resulted in durable improvements in LUTS secondary to BPH in the geriatric population, differences in procedural characteristics and safety profiles across MISTs were considerable. Rezum had the shortest procedure and hospitalization time and lowest occurrence of AEs, while PAE had the longest procedure and hospitalization time and highest occurrence of AEs. Additional studies evaluating Rezum in elderly patients without urinary retention are warranted. Disclosure No.

Emergence of Extended Spectrum β-lactamases producing Escherichia coli among urinary tract infected patients from tertiary hospital in Nepal

Escherichia coli, a growing health concern, produces extended spectrum β-lactamases (ESBL), which are causing public health onset infections in multiple countries. Geographical variations in the distribution and prevalence of ESBL-synthesizing E. coli have been observed, with India reporting the largest proportion (61%). The worldwide dissemination of ESBL-producing bacteria, along with the restricted availability of effective treatments, could exacerbate antibiotic resistance. The identification of ESBL synthesizing E. coli is crucial for its characterisation and epidemiology in specific geographical regions. In Nepal, a developing nation, research shows a high prevalence of antibiotic-resistant bacteria, particularly the ESBL strain. Our study aimed to identify ESBL-producing E. coli from patients with urinary tract complications from a tertiary hospital in Nepal. Out of 125 E. coli isolates, 15.6% were female and 1.2% male. The highest resistance was detected for ampicillin, cefazolin, cefotaxime, and ceftazidime, while less resistance was observed against nitrofurantoin, gentamicin, and imipenem. The study found that 51 (40.8%) E. coli isolates produced ESBLs, indicating a higher level of ESBL production among urinary tract infection patients.

Polypropylene anterior-apical single-incision UPHOLD-LITE mesh surgery in women with severe pelvic organ prolapse: Outcome at 53 months follow up

Background and purposeWe present this current study to complement with mesh inlays plausible benefits (UPHOLD-LITE System) on available long-term study amidst FDA's concern on mesh complications. This study aims to assess the medium-term outcomes of UPHOLD-LITE system for treatment of advanced pelvic organ prolapse (POP) and its complications, and lower urinary tract symptoms. MethodsThis is a retrospective case series of 53 months follow-up of 123 consecutive patients who underwent UPHOLD-LITE system. Objective outcome measures the anatomical correction of prolapse with POP-Q ≤ Stage 1. Subjective outcome was patient's feedback to questions 2 and 3 of POPDI-6. Secondary outcome measures the quality of life, presence of lower urinary tract symptoms and complications. Quality of life is assessed by validated questionnaires on Urogenital Distress Inventory 6 (UDI-6), Incontinence Impact Questionnaire 7 (IIQ-7), Pelvic Organ Prolapse Distress Inventory 6 (POPDI-6), and Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire 12 (PISQ-12) at 1 and 3 years post-operatively. ResultsObjective outcome at 1 and 3 years was at 96.7 % and 95.4 % respectively. The subjective cure was 95.1 % and 91.6 %. Five-year cumulative cure rate maintained at 87.2 %. Secondary outcomes observed improvement on UDI-6, IIQ-7, POPDI-6 and PISQ-12 postoperatively. Bladder outlet obstruction improved while de novo urodynamic stress incontinence (USI) increased slightly post surgically. Mesh erosion rate was 0.8 %. ConclusionThe UPHOLD-LITE system demonstrated good medium term anatomical correction of apical and anterior prolapse, with good subjective cure and improved quality of life. Whilst complication rate was low, slight increase in de novo USI was observed.

Role of Polyomavirus BK and Adenovirus in the Development of Urinary Tract Complications in Pediatric Hematopoietic Stem Cell Transplantation

One of the major challenges in pediatric hematopoietic stem cell transplantation (HSCT) is the susceptibility to viral infections and reactivations that can lead to potentially life-threatening complications and increase the transplant-related mortality (TRM). Polyomavirus BK (BKPyV) and Adenovirus (AdV) represent the predominant causes of urinary tract complications, in particular hemorrhagic cystitis (HC), in HSCT recipients. Treatment options for BKPyV and AdV infections are limited and there is no accepted standard of care for the prevention and treatment of these HSCT complications. The aim of our retrospective study was to analyze the incidence of BKPyV and AdV infection in urinary and plasma samples of pediatric patients undergoing HSCT for both malignant and non-malignant disease at a single pediatric Hematology-Oncology unit. Endpoints were the cumulative incidence of infection, measured on blood and urine samples, in the first 100 days after HSCT, prevalence of asymptomatic and symptomatic infection, and correlation between BKPyV and AdV DNAemia and DNAuria and the development of HC. A total of 79 patients were analyzed. Thirty-seven (47%) patients were positive for BKPyV on urine samples and 20 (30%) on blood samples within the first 30 days after transplantation. As for AdV, 11 (9%) patients were positive on urine samples and 18 (15%) on blood samples. In our pediatric cohort, BKPyV DNAuria was a frequent event after HSCT, while BKPyV DNAemia was observed less frequently, and was accompanied by higher viruria values (p-value &amp;lt;0,001, with a median viral load in the urine of 3.8 x 10 9 copies/mL). Conversely, AdV positivity in urine is rare, while AdV DNAemia was more frequent, due to the modality of BKPyV and AdV distribution (urothelium is the main reservoir for BKPyV, while intestinal lymphocytes represents the main reservoir for AdV). Of the 37 patients with BKPyV DNA on urine samples, 11 (30%) developed a symptomatic infection with grade II (5 patients, 40%) and grade III (6 patients, 60%) HC. We did not observe any correlation between BKPyV DNA urinary levels and the development of HC, as higher viral loads have not been shown to be good predictors of occurrence or severity of HC. Cumulative incidence (CI) of BKPyV infection was higher in haploidentical HSCT (51%) and matched unrelated donors (MUD) (48%) than in HSCT from matched familiar donors (31%). Similarly, CI of AdV reactivation was higher in haploidentical HSCT (16%) than MUD (6%) and matched familiar donors (9%). Choice of donor, the type of immunosuppression used and the intensity of conditioning regimen represented predictors of both blood and urine DNA positivity for both viruses. In our cohort, positivity for BKPyV on blood and/or urine did not increase the risk of transplant-related mortality and did not affect the overall survival after HSCT. On the basis of our data, we now perform screening of BKPyV viruria only in symptomatic patients or in transplant recipients with specific risk factors (type of donor, severity of immunosuppression). Similarly, search for BKPyV DNAemia is reserved to subjects with a high viral load on urine. Likewise, search for AdV on urine samples is performed on symptomatic patients with high-load AdV DNAemia.

Long-Term Non-Congenital Cardiac and Renal Complications in Down Syndrome: A Study of 32,936 Patients.

Individuals with Down syndrome are at a higher risk of cardiac, renal, and other health issues due to a complex disease physiology. However, few data exist on long-term disease risks to guide prevention and care. We aimed to determine the 10-year incidence of cardiac, renal, and urinary tract complications in Down syndrome versus matched controls. This retrospective cohort study utilized a large collaborative database. We identified 32,444 patients with Down syndrome and matched controls, excluding those with pre-follow-up target events. Covariates included demographics, lifestyle factors, and comorbidities. Outcomes were ischemic heart disease, hypertension, hypothyroidism, epilepsy, urinary tract infections and chronic kidney disease. We calculated unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression and plotted Kaplan-Meier survival curves. Over 10 years, Down syndrome patients showed a 3.7-fold higher ischemic heart disease risk (95% CI: 3.0-4.6) and a 1.6-fold higher hypertension risk (95% CI: 1.4-1.8) versus controls. Hypothyroidism (HR = 2.0; 95% CI: 1.7-2.4), epilepsy (HR = 4.5; 95% CI: 3.5-5.8), and urinary tract infection (HR = 3.9; 95% CI: 3.4-4.6) risks were also higher. Chronic kidney disease risk was 2.7-fold greater (95% CI: 2.1-3.5). Survival analysis confirmed a significantly higher incidence of all outcomes in Down syndrome (p < 0.0001). This large study found major health challenges in Down syndrome, with risks 3- to 5-fold higher for chronic conditions versus matched controls over 10 years. Though survival remains high with proper care, focusing resources on the prevention and management of complications in this high-risk group can optimize well-being across the lifespan. Future research accounting for limitations here would provide definitive estimates of disease risk in Down syndrome to guide targeted health strategies.

Schistosoma haematobium urinary tract complications in African migrants attending primary care facilities in Paris, France: A retrospective cohort study (2004–2018)

ObjectivesLittle is known about the burden of urogenital schistosomiasis (UGS) outside endemic areas. This study was aimed at describing urinary complications of UGS detected among African migrants in French primary care facilities. Patients and methodsA retrospective cohort study included patients with UGS diagnosed from 2004 to 2018 in 5 primary health centers in Paris. Cases were defined by the presence of typical Schistosoma haematobium eggs at urine microscopy. Demographic, clinical, biological and imaging data were collected. Ultrasonography (U-S) findings were classified in accordance with the WHO guidelines. ResultsU-S was prescribed for all patients and performed in 100/118. Sex ratio (F/M) was 2/98, and mean age 24.4 years. Patients were from West Africa (73% from Mali) and consulted 8 months (median) after their arrival. Among the 95 patients with interpretable findings, 32 (33.7%) had abnormalities related to UGS, considered as major in 6 cases (6.3%), and mostly localized at the bladder (31/32) without detection of cancer. No sociodemographic, clinical, or biological factors were found to be associated with U-S abnormalities. All 100 patients were treated by praziquantel (PZQ). Among those with abnormalities, 20/32 received two to four doses at various time intervals. Post-cure imaging control performed in 19/32 showed persistent abnormalities in 6 patients, on average 5 months after the last PZQ uptake. ConclusionUrinary tract abnormalities associated with UGS were common and predominated at the bladder. U-S should be prescribed to any patient with positive urine microscopy. Schedules for PZQ uptake and U-S monitoring for patients with complications remain to be determined.

Use of prophylactic ureteral stents in gynecologic surgery.

The aim of this study was to evaluate rate of complications with the use of prophylactic ureteral localization stents (PULSe) in gynecologic surgery. To compare the occurrence of complications according to the indication of surgery. This retrospective study included 1248 women who underwent 1275 different gynecologic surgeries with PULSe between 2007 and 2020. Data was collected regarding patient characteristics (age, sex, race, ethnicity, parity, previous pelvic surgery, creatinine), operative characteristics (trainee, guidewire use, indication) and complications in the first 30 days (ureteral injury, urinary tract complication, re-stenting, hydronephrosis, urinary tract infection (UTI), pyelonephritis, emergency room visit, re-admission). Median age was 57 years (range: 18-96 years), most women were Caucasian (88.9%), and had previous pelvic surgery (77.7%). Indication of surgery was benign for 459 (36.0%), female pelvic medicine and reconstructive surgery (FPMRS) for 545 (42.7%), and gynecologic oncology (gyn-onc) for 271 (21.3%). Disabling complications occurred rarely with 8 patients (0.6%) having a ≥III Clavien Dindo Grade (CDG), and only 1 (0.08%) ≥IV CDG. Statistically significant differences between benign, FPMRS, and gyn-onc groups were noted for re-stenting (0.9% vs. 0.0% vs. 1.1%, P=0.020), hydronephrosis (0.9% vs. 0.2% vs. 2.2%, P=0.014), UTI (4.6% vs. 9.4% vs. 7.0%, P=0.016), and re-admission (2.4% vs. 1.1% vs. 4.4%, P=0.014). The incidence of 30-day CDG III and IV complications after PULSe placement is low. FPMRS patients had a higher rate of complicated UTI, however gyn- onc patients appear to be at overall higher risk of stent related complications when compared to surgeries for FPMRS or benign indications.

Accelerated bacteriological examination of urine and dialysate in the diagnosis of urinary tract infections in children

Aim. To evaluate the feasibility of an accelerated method for determining the etiology of infections in urine, dialysate and residual antimicrobial activity by using laser light scattering technology.Materials and methods. From January to September 2019, 106 urine samples and 42 dialysate samples from children aged 1–16 with various urinary pathologies and those on peritoneal dialysis underwent culture-based examination on an ALIFAX HB&amp;L LIGHT analyzer (Alifax, Italy) using laser light scattering technology.Results. Three hours after inoculation, 81 samples (76.4%) appeared to be negative and 25 samples (23.6%) proved to be positive. No microorganisms were detected in 38 dialysate samples (90.5%), two samples had Staphylococcus aureus (104 CFU/ml), and one dialysate sample had Corynebacterium sp. and associations of Escherichia coli + Candida albicans + Staphylococcus haemolyticus, associated with peritoneal catheter colonization. Bacteriuria was caused by Enterobacterales in 39.3% (E. coli, Morganella morganii, Citrobacter amalonaticus, Enterobacter cloacae), non-fermenting gram-negative bacteria – in 14.3% (Pseudomonas aeruginosa, Ralstonia picketii, Oligella sp., Acinetobacter baumannii), Enterococcus sp. – 21.4%, S. haemolyticus, Staphylococcus epidermidis – 10.7%, Candida albicans – 3.6%, contamination: Streptococcus viridians, Corynebacterium sp. – 7.1%. Residual antimicrobial activity in urine was detected in 30.1% of patients.Conclusion. The laser light scattering technology enables a minimal concentration of microorganisms to be detected in a smaller amount of urine or dialysate, which is very important for accelerated diagnosis of urinary tract infections and complications of peritoneal dialysis in children.

Evaluation of technical urinary tract complications in kidney transplantation recipients with a prolonged dialysis history

BackgroundThe kidney transplant waiting list continues to expand, resulting in prolonged dialysis times exceeding 8 years before transplantation in some regions. The relationship between long-term dialysis and urinary tract complications after kidney transplant remains largely unexplored. This study aims to evaluate post–kidney transplant complications in patients with a history of prolonged dialysis. MethodsA single-center, retrospective cohort study of patients maintained on dialysis ≥8 years before kidney transplant between January 2000 and July 2020 was conducted. Clinical variables, including demographics and comorbidities, were reviewed. The primary objective was the development of a technical urinary tract complication. Secondary outcomes included any postoperative complication by type, stratified by medical and surgical complications. ResultsOverall, 376 patients met the inclusion criteria. The mean pre–kidney transplant dialysis time was 10.2 ± 2.6 years. The majority (65.7%) of the study participants were anuric. Four patients (1.1%) experienced a urine leak, and 8 patients (2.1%) had a ureteral stricture. Any complication was observed in 111 (29.5%) patients, with urinary tract infections being the most common. Urinary catheters remained in place for a median of 4 (3, 5) days. Drains were commonly used (62.8%) for a median of 5 (4, 6) days. ConclusionIn our large, single-center experience with kidney transplants in high-risk patients with prolonged dialysis and anuria, the technical urinary tract complications rate remained low. With the current literature consisting of small cohorts and having relatively short pre–kidney transplant dialysis periods, our analysis addresses the shortcomings of the literature while suggesting that this patient population may not truly be “high risk.”

LONGITUDINAL COMPRESSION THERAPY FOR SMALL BOWEL STRICTURE CROHN'S DISEASE: DURABLE RESOLUTION IN SWINE MODEL

Abstract INTRODUCTION Small bowel stricture is common in Crohn’s disease (CD), both de novo and after resection. With all standard treatments having high recurrence rates, CD patients would benefit greatly from a novel and highly durable non-surgical intervention. We report the first long-term study of longitudinal compression therapy (LCT) for the treatment of anastomotic strictures in an animal CD stricture model. LCT entails progressive endoluminal compression of stricture tissue between two flange-like device components. The goal is to gradually bring about necrosis of fibrotic tissue interposed between the two flanges while allowing remodeling with minimal iatrogenic inflammation around the periphery. METHODS Stable anastomotic strictures with hallmarks of CD small bowel strictures were created in 6 pigs, using an established method entailing ileocolonic anastomosis creation with a bypassed ileal segment to maintain patency of the gastrointestinal tract followed by serial injections of phenol/trinitrobenzenesulfonic acid at the anastomosis site. Instead of using LCT devices deployed wholly endoscopically, to best study stricture response to LCT in this model, we used devices with magnetic elements for compressive force generation and integrated ultraminiature sensor arrays for monitoring treatment progression; one 23 mm diameter device component was placed via a surgical enterotomy and a second was deployed endoscopically. Animals were followed for 9 weeks after LCT to gauge post-treatment stricture response. RESULTS LCT device placement was successful in all animals. Five animals reached the 9-week timepoint. One animal was sacrificed on day 12 due to urinary tract complications unrelated to the device. The initial therapeutic response took place over a 3-hour period after device placement, with LCT devices applying increasing force from 3 to 10 Newtons. In endoscopic assessments, widened lumens were noted, with openings 3.3-fold larger at 2 weeks and 3.7-fold larger at 9 weeks. In comparison, for endoscopic balloon dilation in the same animal stricture model, the openings were 2.3-fold larger at 2 weeks, declining to 1.9-fold at 9 weeks. Endoscopic and macroscopic evaluation after euthanasia demonstrated newly patent lumens after excision of stricture tissue, with healthy-appearing mucosa and no macroscopic findings of stricture. CONCLUSION Prior work by our group and others--in animal models and in a small number of treated patients--has provided favorable indications of efficacy of LCT for treating refractory strictures. To the best of our knowledge, this is the first study to include long-term follow-up of LCT in a validated animal model of Crohn’s stricture. This work provides strong preliminary support that LCT’s combination of resection and neo-epithelialization can durably resolve CD stricture. LCT clinical studies are planned as a next step. Design and operation of device systems for longitudinal compression therapy for small bowel stricture in Crohn’s. (a) Longitudinal compression therapy device systems incorporate a dual-flange design, with a mechanism for drawing the flanges together to longitudinally compress the stricture. For single-sided access, expanding flange designs can be used (inset, top left). The LCT device systems used in this study are pairs of discrete non-expanding flange components, with one flange component placed proximal to the strictured region via laparotomy; magnetic elements in the flange components supply the compressive force. This design facilitates incorporation of ultraminiature sensor arrays into the flange components for monitoring stricture response to treatment (inset bottom right). (b)-(d) Steps in longitudinal compressive therapy: (b) advancing the LCT device through the stricture; (c) stricture compression between distal flange and expanded proximal flanges; (d) completion of therapy. Representative result for LCT in the porcine model of Crohn’s small bowel stricture. (a) Before treatment, a length of bowel 15 mm long is badly strictured, with the lumen less than 10 mm at its narrowest point. (b) At 2 weeks after LCT treatment, the narrowest point is markedly larger. (c) At 9 weeks post LCT treatment—a time after which balloon dilated strictures tend to have recurred—the LCT treated stricture is even more open than at 2 weeks post, consistent with the LCT intervention having spurred healing instead of exacerbating fibrosis. Three-dimensional anatomy of strictured segments determined by impedance-based measurement (Endoflip, Medtronic).

Prevalence of Kidney and Urinary Tract Complications in Fabry Disease from 2000 to 2020: A Global Cohort Study Including 10,637 Patients.

Fabry disease, an X-linked lysosomal storage disorder, causes progressive globotriaosylceramide accumulation in cells throughout the body. Characteristic multiorgan manifestations include renal dysfunction (Fabry nephropathy) and associated urinary tract complications. Enzyme replacement therapy (ERT) has been available since 2001, but contemporary real-world data are lacking regarding Fabry nephropathy risks and treatment outcomes. This retrospective cohort study analyzed electronic medical records data for 10,637 Fabry disease patients from the TriNetX research database. Kidney and urinary tract outcomes were evaluated over two decades, 2000-2010 and 2011-2020. Outcomes assessed included chronic kidney disease (CKD), urinary tract infections, urinary incontinence, obstruction, renal insufficiency, and end-stage renal disease (ESRD). The prevalence of stage 4-5 CKD nearly doubled between 2000-2010 and 2011-2020, while ESRD prevalence rose over 4-fold. Incidence rates showed similar marked elevations across renal and urologic complications. Females and Black patients experienced disproportionate escalations in kidney and urinary tract morbidity. This large cohort study revealed significantly increased Fabry nephropathy and associated urologic complications over the past two decades, contradicting expectations of reduced morbidity with ERT availability. The findings highlight needs to optimize screening, treatment strategies, monitoring practices, and address disparities to curb rising disease burden and improve patient outcomes.

CLL-189 Ibrutinib Treatment and Its Impact on Circulating Immune Cells in Chronic Lymphocytic Leukemia Patients

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized by immune dysregulation, infections represent a cause of mortality and morbidity in CLL. Ibrutinib is a Bruton's tyrosine kinase inhibitor very effective on CLL, but this treatment is burdened by infective complications, especially within the first months of therapy. The decline of infections could suggest that immune competence may be restored by Ibrutinib directly or by reductions in CLL burden. This monocentric prospective study evaluates immunophenotypic changes in circulating immune cells in CLL patients treated with Ibrutinib. We collected peripheral blood samples at baseline, 3, and 6 months of therapy; new samples at 12 and 24 will be collected. Data of 20 patients treated with Ibrutinib in our Centre since January 2021 were collected. Multiparametric flow cytometry was used to characterize immune cells. Median age at Ibrutinib start was 74 years. Nine patients were treatment-naive, 7 were on second-line. The other 4 have already received at least 2 previous therapy lines. In particular, 11 have received chemoimmunotherapy (CIT). The only correlation between clinical-biological data and impact on baseline cells was found between previous exposure to CIT and CD3+HLA-DR+cells (median 1×109/L vs 6×109/L in chemo-naïve patients, p=0.025). No differences in who have received a chemo-free therapy prior to Ibrutinib or based on the number of previous therapy lines. After 6 months of therapy, we observed statistical differences between baseline for CD19+decrease (31×109/L vs 11<109/L, p=0.04). Another difference was found in the decrease of CD3+CD4+count (1×109/L vs 0.76×109/L, p=0.04). Also, the CD3+ count decreased after 6 months (1.7×109/L vs 1.55×109/L, p=0.04). The last significant difference was in the decrease of NK cells (0.5×109/L vs 0.02×109/L, p=0.04). Infectious complication was observed in 8 patients (40%). Specifically, 4 patients experienced COVID-19, 4 pneumonia and one experienced both and a complicated urinary tract infection. These preliminary data show an early reduction of CD4+T-cell subset, dysfunctional in CLL. NKT cells, that mediate tumor immunosurveillance, at baseline were higher than expected but with Ibrutinib they decreased by 59% in 6 months. Further data are needed, but these suggest an impact of Ibrutinib on the immune system that could help on infections.

In vitro activity of imipenem/relebactam against Pseudomonas aeruginosa isolates recovered from ICU patients in Spain and Portugal (SUPERIOR and STEP studies).

To study the in vitro activity of imipenem/relebactam and comparators and the imipenem/relebactam resistance mechanisms in a Pseudomonas aeruginosa collection from Portugal (STEP, 2017-18) and Spain (SUPERIOR, 2016-17) surveillance studies. P. aeruginosa isolates (n = 474) were prospectively recovered from complicated urinary tract (cUTI), complicated intra-abdominal (cIAI) and lower respiratory tract (LRTI) infections in 11 Portuguese and 8 Spanish ICUs. MICs were determined (ISO broth microdilution). All imipenem/relebactam-resistant P. aeruginosa isolates (n = 30) and a subset of imipenem/relebactam-susceptible strains (n = 32) were characterized by WGS. Imipenem/relebactam (93.7% susceptible), ceftazidime/avibactam (93.5% susceptible) and ceftolozane/tazobactam (93.2% susceptible) displayed comparable activity. The imipenem/relebactam resistance rate was 6.3% (Portugal 5.8%; Spain 8.9%). Relebactam restored imipenem susceptibility to 76.9% (103/134) of imipenem-resistant isolates, including MDR (82.1%; 32/39), XDR (68.8%; 53/77) and difficult-to-treat (DTR) isolates (67.2%; 45/67). Among sequenced strains, differences in population structure were detected depending on the country: clonal complex (CC)175 and CC309 in Spain and CC235, CC244, CC348 and CC253 in Portugal. Different carbapenemase gene distributions were also found: VIM-20 (n = 3), VIM-1 (n = 2), VIM-2 (n = 1) and VIM-36 (n = 1) in Spain and GES-13 (n = 13), VIM-2 (n = 3) and KPC-3 (n = 2) in Portugal. GES-13-CC235 (n = 13) and VIM type-CC175 (n = 5) associations were predominant in Portugal and Spain, respectively. Imipenem/relebactam showed activity against KPC-3 strains (2/2), but was inactive against all GES-13 producers and most of the VIM producers (8/10). Mutations in genes affecting porin inactivation, efflux pump overexpression and LPS modification might also be involved in imipenem/relebactam resistance. Microbiological results reinforce imipenem/relebactam as a potential option to treat cUTI, cIAI and LRTI caused by MDR/XDR P. aeruginosa isolates, except for GES-13 and VIM producers.