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BACKGROUND@#Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients’ quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model. @*METHODS@#From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 lg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation. @*RESULTS@#The mean pain scores in the SVF 20 ll group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group.In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group. @*CONCLUSION@#This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.
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BACKGROUND@#Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water.Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN. @*METHODS@#CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration. @*RESULTS@#The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group. @*CONCLUSION@#Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.
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BACKGROUND@#Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water.Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN. @*METHODS@#CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration. @*RESULTS@#The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group. @*CONCLUSION@#Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.
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BACKGROUND@#High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. @*METHODS@#To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. @*RESULTS@#At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. @*CONCLUSION@#IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.
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BACKGROUND@#High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. @*METHODS@#To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. @*RESULTS@#At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. @*CONCLUSION@#IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.
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Purpose@#To evaluate the incidence of de novo overactive bladder (OAB) and the factors related to its occurrence following radical prostatectomy (RP) in patients with clinically localized prostate cancer (PCa). @*Materials and Methods@#We prospectively examined 50 patients without OAB who underwent RP for clinically localized PCa in our institution from August 2019 to February 2020. We performed assessments using the International Prostate Symptom Score (IPSS), the Overactive Bladder Symptom Score (OABSS), and uroflowmetry before surgery and 3 months after RP. OAB was defined as a score of 1 or more on the urgency components of the OABSS. Three months after RP, the patients were divided into 2 groups based on the presence of de novo OAB symptoms. We evaluated the patients’ demographics and outcomes after RP according to their de novo OAB grouping. The predictive factors of de novo OAB after RP were analyzed using a multivariate logistic regression model. @*Results@#Of the 50 patients, 22 (44%) had de novo OAB 3 months after RP. The patients in the de novo OAB group were older, had higher preoperative IPSS storage subscores, and had larger volumes of postvoid residual urine on preoperative uroflowmetry than those in the non-de novo OAB group. Multivariate analysis showed that age and preoperative IPSS storage subscores were predictive factors of de novo OAB after RP. @*Conclusions@#de novo OAB was observed in 44% of the patients 3 months after RP. Age and preoperative IPSS storage subscores were predictive factors of de novo OAB following RP.
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Bleeding from ileal conduit stomal varices is a rare complication. The standard treatment for the management of stomal varices has not been established yet. We present the case of a 65-yearold man with recurrent fatal bleeding from his ileal conduit stomal varices who was successfully treated with ligation of the engorged venous varices using hemostatic agents.
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Human body contains diverse microbes. Different microbes are identified at different organs. Urine was thought as sterile, but according to progression in important technologies like 16S rRNA gene sequencing and expanded quantitative urine culture, it is known that diverse microbes exist in genitourinary tract. Microbiome contains the microbes and surrounding microenvironments. In addition to urologic difficulties like interstitial cystitis or chronic prostatitis, malignancies are thought to be related to microbiomes. In this review, we summarized several studies in urologic malignancies, especially prostate cancer and kidney cancer.
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Purpose@#The survey was conducted on Korean men to examine information acquisition channel for prostate cancer high risk group as part of the “Blue Ribbon Campaign” of the Korean Urological Oncology Society. @*Materials and Methods@#An online survey of 500 men aged 50 years old or older was completed to query investigation of the status of prostate cancer awareness and information acquisition from February 4 to February 9, 2021. @*Results@#Most men in their 50s and older are well aware that prostate cancer can also occur in young men in their 40s, so the rate of misunderstanding of the timing of prostate cancer screening after their 60s is very low. Two-thirds of all respondents (67.2%) were also confirmed that prostate cancer had no initial symptoms and was not included in the national cancer screening. Seventy-five percent of people look up information on their own in case of suspected prostate cancer, and 51.6% seek out knowledge on their own to prevent prostate cancer. Of the respondents, 27.4% of men contacted prostate cancer-related information within the past year, and the percentage of people contacted through ‘Internet/Phone,’ ‘People Around’ and ‘Television’ was high. The most trusted channel among prostate cancer information channels was ‘medical professionals,’ but the experience rate was not high, and the channel with high experience rate and reliability was shown as ‘television.’ @*Conclusions@#Much effort is still needed to understand the information acquisition behavior of Korean men and to improve awareness of early screening for prostate cancer.
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Purpose@#To evaluate the incidence of de novo overactive bladder (OAB) and the factors related to its occurrence following radical prostatectomy (RP) in patients with clinically localized prostate cancer (PCa). @*Materials and Methods@#We prospectively examined 50 patients without OAB who underwent RP for clinically localized PCa in our institution from August 2019 to February 2020. We performed assessments using the International Prostate Symptom Score (IPSS), the Overactive Bladder Symptom Score (OABSS), and uroflowmetry before surgery and 3 months after RP. OAB was defined as a score of 1 or more on the urgency components of the OABSS. Three months after RP, the patients were divided into 2 groups based on the presence of de novo OAB symptoms. We evaluated the patients’ demographics and outcomes after RP according to their de novo OAB grouping. The predictive factors of de novo OAB after RP were analyzed using a multivariate logistic regression model. @*Results@#Of the 50 patients, 22 (44%) had de novo OAB 3 months after RP. The patients in the de novo OAB group were older, had higher preoperative IPSS storage subscores, and had larger volumes of postvoid residual urine on preoperative uroflowmetry than those in the non-de novo OAB group. Multivariate analysis showed that age and preoperative IPSS storage subscores were predictive factors of de novo OAB after RP. @*Conclusions@#de novo OAB was observed in 44% of the patients 3 months after RP. Age and preoperative IPSS storage subscores were predictive factors of de novo OAB following RP.
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Bleeding from ileal conduit stomal varices is a rare complication. The standard treatment for the management of stomal varices has not been established yet. We present the case of a 65-yearold man with recurrent fatal bleeding from his ileal conduit stomal varices who was successfully treated with ligation of the engorged venous varices using hemostatic agents.
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Human body contains diverse microbes. Different microbes are identified at different organs. Urine was thought as sterile, but according to progression in important technologies like 16S rRNA gene sequencing and expanded quantitative urine culture, it is known that diverse microbes exist in genitourinary tract. Microbiome contains the microbes and surrounding microenvironments. In addition to urologic difficulties like interstitial cystitis or chronic prostatitis, malignancies are thought to be related to microbiomes. In this review, we summarized several studies in urologic malignancies, especially prostate cancer and kidney cancer.
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Purpose@#The survey was conducted on Korean men to examine information acquisition channel for prostate cancer high risk group as part of the “Blue Ribbon Campaign” of the Korean Urological Oncology Society. @*Materials and Methods@#An online survey of 500 men aged 50 years old or older was completed to query investigation of the status of prostate cancer awareness and information acquisition from February 4 to February 9, 2021. @*Results@#Most men in their 50s and older are well aware that prostate cancer can also occur in young men in their 40s, so the rate of misunderstanding of the timing of prostate cancer screening after their 60s is very low. Two-thirds of all respondents (67.2%) were also confirmed that prostate cancer had no initial symptoms and was not included in the national cancer screening. Seventy-five percent of people look up information on their own in case of suspected prostate cancer, and 51.6% seek out knowledge on their own to prevent prostate cancer. Of the respondents, 27.4% of men contacted prostate cancer-related information within the past year, and the percentage of people contacted through ‘Internet/Phone,’ ‘People Around’ and ‘Television’ was high. The most trusted channel among prostate cancer information channels was ‘medical professionals,’ but the experience rate was not high, and the channel with high experience rate and reliability was shown as ‘television.’ @*Conclusions@#Much effort is still needed to understand the information acquisition behavior of Korean men and to improve awareness of early screening for prostate cancer.
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Background@#Tissue engineering can be used for bladder augmentation. However, conventional scaffolds result in fibrosis and graft shrinkage. This study applied an alternative polycaprolactone (PCL)-based scaffold (diameter = 5 mm) with a noble gradient structure and growth factors (GFs) (epidermal growth factor, vascular endothelial growth factor, and basic fibroblast growth factor) to enhance bladder tissue regeneration in a rat model. @*Methods@#Partially excised urinary bladders of 5-week-old male Slc:SD rats were reconstructed with the scaffold (scaffold group) or the scaffold combined with GFs (GF group) and compared with sham-operated (control group) and untreated rats (partial cystectomy group). Evaluations of bladder volume, histology, immunohistochemistry (IHC), and molecular markers were performed at 4, 8, and 12 weeks after operation. @*Results@#The bladder volumes of the scaffold and GF group recovered to the normal range, and those of the GF group showed more enhanced augmentation. Histological evaluations revealed that the GF group showed more organized urothelial lining, dense extracellular matrix, frequent angiogenesis, and enhanced smooth muscle bundle regeneration than the scaffold group. IHC for α-smooth muscle actin, pan-cytokeratin, α-bungarotoxin, and CD8 revealed that the GF group showed high formation of smooth muscle, blood vessel, urothelium, neuromuscular junction and low immunogenicity. Concordantly, real-time polymerase chain reaction experiments revealed that the GF group showed a higher expression of transcripts associated with smooth muscle and urothelial differentiation. In a 6-month in vivo safety analysis, the GF group showed normal histology. @*Conclusion@#This study showed that a PCL scaffold with a gradient structure incorporating GFs improved bladder regeneration functionally and histologically.
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Purpose@#To determine an appropriate surgical technique, it is important to predict pathological results for patientswith clinically localized prostate cancer (PCa) eligible for nerve-sparing radical prostatectomy (NSRP). Severalstudies have highlighted that serum testosterone level was associated with aggressive features of PCa. Therefore,we analyzed factors, including serum testosterone, to predict upstaging and upgrading after surgery for patientswith clinically localized PCa eligible for NSRP. @*Materials and Methods@#We retrospectively evaluated patients who underwent radical prostatectomy (RP) betweenJanuary 2015 and May 2018 at our institution. Patients with Gleason grade group 1 or 2 on biopsy,prostate-specific antigen<10, and ≤clinical/radiologic stage T2 were included in this study. Upstaging andupgrading were defined as pathological stage≥T3a and Gleason grade group≥3, respectively. We evaluatedthe patients’ demographics and outcomes according to upstaging and upgrading after surgery. Predictive factorsfor upstaging and upgrading were analyzed using a multivariate logistic regression model. @*Results@#Of 108 patients included in the study, upstaging and upgrading after surgery were observed in 24 (22.2%)and 36 (33.3%), respectively. Low serum testosterone level, small prostate size, and positive core number≥3on biopsy were identified as predictive factors for upstaging in multivariate analysis. Although serum testosteronewas associated with upgrading in univariate analysis, only clinical/radiologic stage and biopsy Gleason grade groupwere observed as predictive factors for upgrading in multivariate analysis. @*Conclusions@#Serum testosterone level was identified as a predictive factor for upstaging after RP for clinicallylocalized PCa eligible for NSRP.
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Muscle-invasive bladder cancer (MIBC) is classified into a heterogeneous life-threatening epithelial tumor with a high rate of metastasis and a dismal survival rate. Dissimilarity in genetic or epigenetic environment of MIBC causes considerable uncertainty in cancer aggressiveness, progression, and response rates, representing this cancer especially tough to manage. Several definite cases consist of point mutations in genes encoding receptor tyrosine or cytosolic kinases and alterations in epigenetics machinery, including both methylated genes and respective effector enzymes. Considering the highly aggressive and invasive character of MIBC, various attempts have been made to accurately detect and treat the disease using radical cystectomy alone or in combination with adjuvant chemo- and/or radiotherapy including neo-adjuvant chemotherapy. Nowadays advances in the field of immunotherapy with the introduction of checkpoint inhibitors have led to paradigm shifts in the treatment of MIBC. In current review, several published biological markers were introduced from diverse experimental techniques including gene expression profiling, mutations, single nucleotide polymorphisms, and epigenetic alterations. Moreover, the clinical evidence of new therapeutic targets with focus on checkpoint inhibitor in MIBC was summarized. These markers may be the excellent tools to predict MIBC prognosis and drug-responsiveness in the near future. (Korean J Urol Oncol 2020;18:1-10)
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Purpose@#The aim of this study was to analyze the perioperative complications and oncological outcomes of radical prostatectomy (RP) in patients who underwent multiple prostate biopsies. @*Materials and Methods@#A total of 1,112 patients who underwent RP between January 2009 and April 2016 at 4 different centers were included in this study. We divided these patients into 2 groups: patients who underwent only 1st biopsy, and those who underwent 2nd or more repeated biopsies. The association between the number of prior biopsies and perioperative complications and biochemical recurrence (BCR) was analyzed. @*Results@#Of 1,112 patients, 1,046 patients (94.1%) underwent only 1st biopsy, and 66 (5.9%) underwent 2nd or more repeated biopsies. There were no significant differences in preoperative prostate-specific antigen levels, operation times, blood loss volumes, or hospital stay durations (all p＞0.05). Patients who underwent multiple prostate biopsies presented with a localized tumor significantly more often (p＜0.05). The Gleason score and rate of positive surgical margins were significantly lower in patients with multiple biopsies (all p＜0.05). The Cox proportional hazards model analysis indicated that there was no association between the number of prior prostate biopsies and BCR (p＞0.05). Kaplan-Meier curve analysis indicated that BCR-free survival rates between the 2 groups were similar (p＞0.05). @*Conclusions@#Multiple prostate biopsies are not associated with an increased risk of perioperative complications, adverse pathological outcomes, or higher rates of BCR in patients who have undergone RP. (Korean J Urol Oncol 2020;18:24-31)
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PURPOSE: The purpose of this study was to determine the comparative effectiveness of androgen deprivation therapy (ADT) combined with docetaxel (DTX)-based chemotherapy in Korean and Japanese castration-resistant prostate cancer (CRPC) patient cohorts.MATERIALS AND METHODS: Metastatic CRPC patients who underwent more than three DTX-based chemotherapy cycles in Korea and Japan between 2002 and 2017 were retrospectively analyzed and divided into the DTX-only (DTX, n=30) and combination (DTX+ADT, n=46) groups. Progression-free survival (PFS) was calculated as the time from the start of chemotherapy to the occurrence of either disease progression (prostate-specific antigen [PSA] progression or radiographic progression) or death. The primary end point was PFS and the secondary end point was overall survival (OS).RESULTS: In the DTX and DTX+ADT groups, the median PFS was 6.0 and 11.0 months (log-rank p=0.053). The multivariate Cox regression analysis revealed that the significant predicting factors of PFS were ADT administration (hazard ratio [HR], 0.478; 95% confidence interval [CI], 0.284–0.804; p=0.005) and number of DTX-based chemotherapy cycles (HR, 0.934; 95% CI, 0.899–0.970; p<0.001). In the DTX and DTX+ADT groups, the median OS was 16.0 and 19.5 months (log-rank p=0.825). Through multiple Cox regression analysis, we found that the significant predicting factors of OS were the PSA nadir level (HR, 1.001; 95% CI, 1.000–1.002; p<0.001) and number of DTX-based chemotherapy cycles (HR, 0.932; 95% CI, 0.876–0.991; p=0.024).CONCLUSIONS: Concurrent DTX-based chemotherapy and ADT may be beneficial compared with DTX-based chemotherapy alone in chemotherapy-naïve metastatic CRPC patients in terms of the PFS, but not the OS.
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BACKGROUND: Despite major progress in stem cell therapy, our knowledge of the characteristics and tissue regeneration potency of long-term transported cells is insufficient. In a previous in vitro study, we established the optimal cell transport conditions for amniotic fluid stem cells (AFSCs). In the present study, the target tissue regeneration of long-term transported cells was validated in vivo. METHODS: For renal regeneration, transported AFSCs were seeded on a poly(lactide-co-glycolide) scaffold and implanted in a partially resected kidney. The target tissue regeneration of the transported cells was compared with that of freshly harvested cells in terms of morphological reconstruction, histological microstructure reformation, immune cell infiltration, presence of induced cells, migration into remote organs, expression of inflammation/fibrosis/renal differentiation-related factors, and functional recovery. RESULTS: The kidney implanted with transported cells showed recovery of total kidney volume, regeneration of glomerular/renal tubules, low CD4/CD8 infiltration, and no occurrence of cancer during 40 weeks of observation. The AFSCs gradually disappeared and did not migrate into the liver, lung, or spleen. We observed low expression levels of proinflammatory cytokines and fibrotic factors; enhanced expression of the genes Wnt4, Pax2, Wt1, and Emx2; and significantly reduced blood urea nitrogen and creatinine values. There were no statistical differences between the performance of freshly harvested cells and that of the transported cells. CONCLUSION: This study demonstrates that long-term transported cells under optimized conditions can be used for cell therapy without adverse effects on stem cell characteristics, in vivo safety, and tissue regeneration potency.
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Femenino , Líquido Amniótico , Nitrógeno de la Urea Sanguínea , Tratamiento Basado en Trasplante de Células y Tejidos , Creatinina , Citocinas , Técnicas In Vitro , Riñón , Hígado , Pulmón , Poliglactina 910 , Regeneración , Bazo , Células MadreRESUMEN
BACKGROUND: Few studies have reported on breakthrough urinary tract infection (UTI) associated with the susceptibility of index UTI to prophylactic antibiotics in children with primary vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). We assessed the impact of the susceptibility of index UTI to prophylactic antibiotics in breakthrough UTIs in children with primary VUR receiving CAP. METHODS: We retrospectively reviewed the medical records of 81 children with primary VUR who were diagnosed after febrile or symptomatic UTI and subsequently received trimethoprim-sulfamethoxazole (TMP-SMX) as CAP between January 2010 and December 2013. We allocated children to a susceptible group or a resistant group based on the susceptibility of index UTI to TMP-SMX. We evaluated patient demographics and clinical outcomes after CAP according to the susceptibility of index UTI to TMP-SMX. Multivariate analysis was used to identify the predictive factors for breakthrough UTI. RESULTS: Of the 81 children, 42 were classified into the susceptible group and 39 into the resistant group. The proportion of breakthrough UTI was 31.0% (13/42) in the susceptible group and 53.8% (21/39) in the resistant group (P = 0.037). Progression of renal scarring was observed in 0% of children in the susceptible group and 15% in the resistant group (P = 0.053). Multivariate analysis showed that TMP-SMX resistance and initial renal scarring were significant predictors of breakthrough UTI. CONCLUSION: Susceptibility of index UTI to prophylactic antibiotics is a risk factor of breakthrough UTI and is associated with poor clinical outcomes in children with primary VUR receiving CAP.