Systematic review of the utilization of botulinum toxin in Mohs micrographic surgery.

The use of botulinum toxin for off-label indications has become more prevalent, but the specific benefits in Mohs micrographic surgery (MMS) have not yet been fully elucidated. A systematic review was performed of PubMed, Cochrane, EMBASE, and Scopus databases to identify all articles describing the use of botulinum toxin in MMS. Analysis was subdivided into scar minimization, parotid injury, and pain management. A total of nine articles were included. Scar minimization and treatment of parotid injury were the most reported uses. One case reported the use of botulinum toxin for pain management. Off label uses of botulinum toxin are being explored. Additional research is warranted to determine the efficacy and utility of botulinum toxin in MMS.

3D printing of Rg3-loaded hydrogel scaffolds: anti-inflammatory and scar-formation related collagen inhibitory effects for scar-free wound healing.

During the process of wound healing, the stimulation of inflammatory factors often leads to abnormal proliferation of blood vessels and collagen, ultimately resulting in scar formation. To address this challenge, we fabricate a novel dermal extracellular matrix (DECM) hydrogel scaffold loaded with ginsenoside Rg3 (Rg3) using 3D printing technology. Mesoporous silica nanoparticles (MSNs) are introduced into the system to encase the Rg3 to control its release rate and enhance its bioavailability. We systematically evaluate the biological, physicochemical, and wound healing properties of this scaffold. In vitro studies demonstrate that the hydrogel exhibits excellent biocompatibility and solid-like rheological properties, ensuring its successful printing. In vivo studies reveal that the composite hydrogel scaffolds effectively accelerate wound healing and achieve scar-free wound healing within three weeks. Histological and immunohistochemical (IHC) analyses show that the composite hydrogel scaffolds reduce the inflammatory response and inhibit excessive collagen accumulation. These combined effects underscore the potential of our approach in effectively inhibiting scar formation.

An injectable thermoresponsive-hydrogel for lamellar keratoplasty: In-situ releases celastrol and hampers corneal scars.

Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. In situ delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with in situ drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The in-situ gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. In vivo evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis via mTORC1 signal promoting autophagy and inhibiting TGF-ß1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.

Long-Term Protective Effects of Succinate Dehydrogenase Inhibition during Reperfusion with Malonate on Post-Infarction Left Ventricular Scar and Remodeling in Mice.

Succinate dehydrogenase inhibition with malonate during initial reperfusion reduces myocardial infarct size in both isolated mouse hearts subjected to global ischemia and in in situ pig hearts subjected to transient coronary ligature. However, the long-term effects of acute malonate treatment are unknown. Here, we investigated whether the protective effects of succinate dehydrogenase inhibition extend to a reduction in scar size and adverse left ventricular remodeling 28 days after myocardial infarction. Initially, ten wild-type mice were subjected to 45 min of left anterior descending coronary artery (LAD) occlusion, followed by 24 h of reperfusion, and were infused during the first 15 min of reperfusion with saline with or without disodium malonate (10 mg/kg/min, 120 µL/kg/min). Malonate-treated mice depicted a significant reduction in infarct size (15.47 ± 3.40% of area at risk vs. 29.34 ± 4.44% in control animals, p < 0.05), assessed using triphenyltetrazolium chloride. Additional animals were then subjected to a 45 min LAD ligature, followed by 28 days of reperfusion. Treatment with a single dose of malonate during the first 15 min of reperfusion induced a significant reduction in scar area, measured using Picrosirius Red staining (11.94 ± 1.70% of left ventricular area (n = 5) vs. 23.25 ± 2.67% (n = 9), p < 0.05), an effect associated with improved ejection fraction 28 days after infarction, as determined using echocardiography, and an attenuated enhancement in expression of the pro-inflammatory and fibrotic markers NF-κB and Smad2/3 in remote myocardium. In conclusion, a reversible inhibition of succinate dehydrogenase with a single dose of malonate at the onset of reperfusion has long-term protective effects in mice subjected to transient coronary occlusion.

Evaluating the impact of recombinant human epidermal growth factor on scar formation in oral and maxillofacial traumatic wound healing.

Scarring following oral and maxillofacial trauma can have significant aesthetic and functional repercussions. Recombinant human epidermal growth factor (rhEGF) has emerged as a potential therapeutic agent to enhance wound healing and minimise scar formation. This retrospective study analysed data from March 2020 to June 2023 at a single institution. A total of 105 patients were divided into a control group (n = 70) receiving standard treatment and an observation group (n = 35) receiving standard treatment plus rhEGF. The primary outcomes were the incidence of scar hyperplasia and infection rates, with the secondary outcome being scar aesthetics measured by the visual analogue scale (VAS). No significant differences were found in baseline characteristics between the two groups. The observation group showed a significant reduction in scar hyperplasia (14.3% vs. 57.1%, χ2 = 20.98, p < 0.01) and infection rates (5.7% vs. 21.4%, χ2 = 4.246, p < 0.05) compared to the control group. VAS scores indicated a superior aesthetic outcome in the observation group at all post-treatment timepoints (p < 0.01). rhEGF treatment in oral and maxillofacial trauma patients resulted in favourable healing outcomes and reduced scar formation, improving aesthetic results. These findings highlight the therapeutic potential of rhEGF and underscore the need for larger-scale trials to further investigate its benefits.

TANGO1 inhibitors reduce collagen secretion and limit tissue scarring.

Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We have designed membrane permeant peptide inhibitors that specifically target the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Application of the peptide inhibitors leads to reduced TANGO1 and cTAGE5 protein levels and a corresponding inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish results in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduce secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, targeted interference of the TANGO1-cTAGE5 binding interface could enable therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.

Efficacy and safety of endoscopic cardia peripheral tissue scar formation (ECSF) for the treatment of refractory gastroesophageal reflux disease: A systematic review with meta-analysis.

BACKGROUND: Endoscopic treatment is increasingly used for refractory gastroesophageal reflux disease (rGERD). Unlike the mechanism of conventional surgical fundoplication, gastroesophageal junction ligation, anti-reflux mucosal intervention, and radiofrequency ablation have extremely similar anti-reflux mechanisms; hence, we collectively refer to them as endoscopic cardia peripheral tissue scar formation (ECSF). We conducted a systematic review and meta-analysis to assess the safety and efficacy of ECSF in treating rGERD. METHODS: We performed a comprehensive search of several databases, including PubMed, Embase, Medline, China Knowledge Network, and Wanfang, to ensure a systematic approach for data collection between January 2011 and July 2023. Forest plots were used to summarize and combine the GERD-health-related quality of life (HRQL), gastroesophageal reflux questionnaire score, and DeMeester scores, acid exposure time, lower esophageal sphincter pressure, esophagitis, proton pump inhibitors use, and patient satisfaction. RESULTS: This study comprised 37 studies, including 1732 patients. After ECSF, significant improvement in gastroesophageal reflux disease health-related quality of life score (mean difference [MD] = 18.27 95% CI: 14.81-21.74), gastroesophageal reflux questionnaire score (MD = 4.85 95% CI: 3.96-5.75), DeMeester score (MD = 42.34, 95% CI: 31.37-53.30), acid exposure time (MD = 7.98, 95% CI: 6.03-9.92), and lower esophageal sphincter pressure was observed (MD = -5.01, 95% CI: -8.39 to 1.62). The incidence of serious adverse effects after ECSF was 1.1% (95% CI: 0.9%-1.2%), and postoperatively, 67.4% (95% CI: 66.4%-68.2%) of patients could discontinue proton pump inhibitor-like drugs, and the treatment outcome was observed to be satisfactory in over 80% of the patients. Subgroup analyses of the various procedures showed that all 3 types improved several objective or subjective patient indicators. CONCLUSIONS: Based on the current meta-analysis, we conclude that rGERD can be safely and effectively treated with ECSF as an endoscopic procedure.

Snail extract for skin: A review of uses, projections, and limitations.

BACKGROUND: Snail mucin is becoming increasingly popular for its wide range of ingredients and potential benefits. Snail extract's widespread appearance in cosmetic formulations encourages an investigation into the medical and cosmetic benefits. AIMS: This study aims to explore current literature on the variety of snail mucin applications. Specifically, we present a review of the uses, global market estimates and projects, and limitations to snail mucin. METHODS: A literature search was conducted on PubMed reviewing snail mucin and their application in medical and dermatologic fields examining their uses. Economic reports were also investigated for Global Market estimates. RESULTS: The therapeutic use of snail mucin in medical fields has been studied as antimicrobial agents, drug delivery vehicles, antitumor agents, wound healing agents, and biomaterial coatings among others. Additionally, the use in cosmetic fields includes antiaging, hydrating, anti-acne, scarring, and hyperpigmentation treatments. It is important to highlight that most studies conducted were preclinical or small clinical studies, stressing the need for additional large-scale clinical trials to support these claims. Investigations into the global market found estimates ranging from $457 million to $1.2 billion with upward projections in the upcoming decade. Limitations include ethical habitats for collection, allergy investigation, and missing clinical studies. CONCLUSIONS: The findings presented here emphasize the expanding uses of snail mucin and its ingredients alongside a growing market cosmetic industry should consider. We also emphasize the need for appropriate clinical trials into the stated benefits of snail mucin to ensure consumer safety and ethical extraction of mucin.

Safety and Efficacy of Minoxidil Treatment in Scarring Alopecia: A Scoping Review.

BACKGROUND: Topical minoxidil (TM) has been a cornerstone in treating various hair loss disorders, while low-dose oral minoxidil (LDOM) is emerging as an effective alternative. Despite their widespread use, there is a notable gap in the literature regarding their use in treating scarring alopecia. OBJECTIVE: This study evaluates the efficacy and safety of TM and LDOM in managing scarring alopecia. METHODS: A systematic literature search identified relevant studies on TM and LDOM use in central centrifugal cicatricial alopecia, frontal fibrosing alopecia, lichen planopilaris, and traction alopecia. Key metrics included disease stabilization, hair thickness improvement, hair regrowth, and side effect profiles. RESULTS: Analysis of the selected studies revealed mixed outcomes. Most participants experienced benefits in terms of disease stabilization and hair regrowth with TM and LDOM. The majority of cases reported good tolerability of the treatment, although some side effects were noted. CONCLUSION: TM and LDOM show promise in scarring alopecia treatment, demonstrating benefits in disease stabilization and hair regrowth. Despite these positive indications, the variability in results and reported side effects underline the need for further research to establish their consistent efficacy and safety profiles in scarring alopecia treatment. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7743.

A review of isotretinoin in the treatment of frontal fibrosing alopecia.

INTRODUCTION: Frontal fibrosing alopecia (FFA) is characterized by scarring alopecia of the frontotemporal scalp and facial papules. Isotretinoin is a vitamin A-derived retinoid discovered in 1955 and approved for treating nodulocystic acne. This drug can also affect facial papules and frontotemporal hair loss in patients with FFA. In this article, we conducted a review of the available studies investigating the use of oral isotretinoin for FFA treatment. Our study provides insights into the efficacy and safety of isotretinoin as a potential treatment option for FFA and highlights areas for future research. METHOD: In this study, we aimed to investigate the potential advantages and disadvantages of isotretinoin as a treatment for FFA. To identify all relevant articles, we developed a comprehensive search strategy and conducted a thorough search of three major databases: PubMed, Embase, and Science Direct. We retrieved a total of 82 articles from the search results. Two independent reviewers then screened each of the 82 articles based on our inclusion and exclusion criteria, resulting in the identification of 15 articles that were deemed relevant to our study. RESULTS: Across the 15 articles, 232 patients who suffered from FFA were involved. Nearly 90% of patients experienced a significant reduction of symptoms after receiving oral isotretinoin at 10-40 mg daily. We conclude that isotretinoin can positively affect facial papules and help suppress hair loss.

Botulinum toxin type A inhibits M1 macrophage polarization by deactivation of JAK2/STAT1 and IκB/NFκB pathway and contributes to scar alleviation in aseptic skin wound healing.

The non-neuronal and non-muscular effects of botulinum toxin type A (BTXA) on scar reduction has been discovered. This study was designed to investigate the effects of BTXA on macrophages polarization during the early stage of skin repair. A skin defect model was established on the dorsal skin of SD rats. BTXA was intracutaneous injected into the edge of wound immediately as the model was established. Histological examinations were performed on scar samples. Raw 264.7 was selected as the cell model of recruited circulating macrophages, and was induced for M1 polarization by LPS. Identify the signaling pathways that primarily regulated M1 polarization and respond to BTXA treatment. Application of BTXA at early stage of injury significantly reduced the scar diameter without delaying wound closure. BTXA treatment improved fiber proliferation and arrangement, and inhibited angiogenesis in scar granular tissue. The number of M1 macrophages and the levels of pro-inflammation were decreased after treated with BTXA in scar tissues. LPS activated JAK2/STAT1 and IκB/NFκB pathways were downregulated by BTXA, as well as LPS induced M1 polarization. At early stage of skin wound healing, injection of BTXA effectively reduced the number of M1 macrophages and the levels of pro-inflammatory mediators which contributes to scar alleviation. BTXA resisted the M1 polarization of macrophages induced by LPS via deactivating the JAK2/STAT1 and IκB/NFκB pathways.

Endotracheal tubes with dexamethasone eluting electrospun coating improve tissue mechanical function after upper airway injury.

Corticosteroid-eluting endotracheal tubes (ETTs) were developed and employed in a swine laryngotracheal injury model to maintain airway patency and provide localized drug delivery to inhibit fibrotic scarring. Polycaprolactone (PCL) fibers with or without dexamethasone were electrospun onto the ETT surface PCL-only coated ETTs and placed in native airways of 18 Yorkshire swine. Regular and dexamethasone-PCL coated ETTs were placed in airways of another 18 swine injured by inner laryngeal mucosal abrasion. All groups were evaluated after 3, 7 and 14 days (n = 3/treatment/time). Larynges were bisected and localized stiffness determined by normal indentation, then sequentially matched with histological assessment. In the native airway, tissue stiffness with PCL-only ETT placement increased significantly from 3 to 7 days (p = 0.0016) and 3 to 14 days (p < 0.0001) while dexamethasone-PCL ETT placement resulted in stiffness decreasing from 7 to 14 days (p = 0.031). In the injured airway, localized stiffness at 14 days was significantly greater after regular ETT placement (23.1 ± 0.725 N/m) versus dexamethasone-PCL ETTs (17.10 ± 0.930 N/m, p < 0.0001). Dexamethasone-loaded ETTs were found to reduce laryngotracheal tissue stiffening after simulated intubation injury compared to regular ETTs, supported by a trend of reduced collagen in the basement membrane in injured swine over time. Findings suggest localized corticosteroid delivery allows for tissue stiffness control and potential use as an approach for prevention and treatment of scarring caused by intubation injury.

Searching for a "Window of Opportunity" in the Treatment of Vulvar Lichen Sclerosus: Evidence for Therapeutic Benefits of an Early Corticosteroid Treatment.

INTRODUCTION: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a "window of opportunity" exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs. METHODS: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016-2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation. RESULTS: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy. CONCLUSION: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a "window of opportunity" in VLS treatment.

Evaluation and comparison of the efficacy and safety of cross-linked and non-cross-linked hyaluronic acid in combination with botulinum toxin type A in the treatment of atrophic acne scars: A double-blind randomized clinical trial.

INTRODUCTION: Acne vulgaris is a common skin condition that affects a significant percentage of adolescents, with scarring being one of its permanent complications. This study aims to compare the efficacy and safety of using botulinum toxin type A (BTA) in combination with cross-linked and non-cross-linked hyaluronic acid (HA) for the treatment of atrophic acne scars. METHOD: Our study is a randomized, double-blind clinical trial conducted on 16 patients with atrophic acne scars. The patients were randomly assigned to one of two groups: one group received a single session of BTA and crossed link HA combination, while the other group received two sessions of BTA and non-crossed link HA, 1 month apart. The patients were followed up at 3 and 6 months after baseline to evaluate the number and area of fine and large pores and spots, scar grading, patient satisfaction, and complications. RESULTS: The mean age of individuals in both the cross-linked HA and non-cross-linked HA groups was 32.75 ± 4.26 and 31.50 ± 8.48 years, respectively (p = 0.71). In terms of gender, three (37.5%) and seven (87.5%) individuals in the cross-linked and non-cross-linked HA groups were female, respectively (p = 0.11). There were no significant differences in the count and area of fine and large pores and spots between the two groups at baseline and the first follow-up session. However, in the second follow-up session, the non-cross-linked HA group had significantly better results than the cross-linked HA group in terms of large pores count and area (p = 0.01). In terms of changes over time, the non-cross-linked HA group showed significantly better improvements in the count and area of large pores compared to the cross-linked HA group (p = 0.03). Additionally, both groups experienced a significant decrease in the count and area of fine pores over time (p = 0.001), but the amount of changes was not statistically significant between the two groups (p = 0.06). Concerning acne grade, initially, 62.5% and 12.5% of cases in the cross-linked HA and non-cross-linked HA groups, respectively, had severe grades. However, in the last session, these percentages significantly decreased to 0% for both groups (p = 0.002 and 0.005, respectively). In terms of treatment complications, none of the patients experienced any adverse effects. CONCLUSION: The study demonstrated that both cross-linked HA and non-cross-linked HA were effective in reducing acne severity and improving the appearance of pores and spots. The treatments had similar effects on fine pores, spots, and overall acne severity. However, non-cross-linked HA appeared to have a better result on large pores compared to cross-linked HA.

Evaluating the efficacy of recombinant human growth factors in scar remodelling for patients with facial soft tissue injuries.

Facial soft tissue injuries, often resulting in scarring, pose a challenge in reconstructive and aesthetic surgery due to the need for functional and aesthetic restoration. This study evaluates the efficacy of recombinant human growth factors (rhGFs) in scar remodelling for such injuries. A retrospective evaluation was conducted from January 2020 to January 2023, involving 100 patients with facial soft tissue injuries. Participants were divided equally into a control group, receiving standard cosmetic surgical repair, and an observation group, treated with rhGFs supplemented cosmetic surgery. The study assessed scar characteristics (pigmentation, pliability, vascularity, height), hospital stay duration, tissue healing time, complication rates and patient satisfaction. The observation group demonstrated significant improvements in all scar characteristics, with notably better pigmentation, pliability, vascularity and height compared with the control group. The rhGF treatment also resulted in reduced hospital stay duration and faster tissue healing. Notably, the total complication rate was significantly lower in the observation group (10%) compared with the control group (34%). Additionally, patient satisfaction levels were higher in the observation group, with 98% combined satisfaction compared with 76% in the control group. The application of rhGFs in treating facial soft tissue injuries significantly enhances scar remodelling, expedites healing, reduces complications and improves patient satisfaction. These findings establish rhGFs as a valuable tool in the management of facial soft tissue injuries, highlighting their potential in improving both functional and aesthetic outcomes.

A MEK inhibitor arrests the cell cycle of human conjunctival fibroblasts and improves the outcome of glaucoma filtration surgery.

Better agents are needed to improve glaucoma filtration surgery outcomes compared to current ones. The purpose of this study is to determine whether mitogen-activated protein kinase kinase (MEK) inhibitors can effectively arrest the cell cycle of human conjunctival fibroblasts (HCFs) and inhibit the formation of fibrosis and scarring following glaucoma filtration surgery. A cell counting kit­8 assay revealed that the MEK inhibitor PD0325901 exhibited concentration-dependent growth inhibition of HCFs. Quantitative PCR, immunocytochemistry, and western blotting demonstrated decreased expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 and increased expression of p27 in HCFs treated with PD0325901. Flow cytometry indicated that PD0325901 arrested the cell cycle of HCFs in the G0/1 phase. The cell-migration assay showed that HCF migration rate was significantly suppressed by PD0325901 exposure. Rabbits were divided into PD0325901-treatment and control groups, and glaucoma filtration surgery was performed. Although intraocular pressure did not differ between PD0325901-treatment and control groups, bleb height was greater in the treatment group. Histopathological evaluation revealed that fibrotic changes were significantly attenuated in the PD0325901-treatment group compared to the control group. In conclusion, the MEK inhibitor impedes HCF proliferation via cell-cycle arrest and may be beneficial for glaucoma filtration surgery by reducing bleb scarring.

Risk factors for new renal scarring in children with vesicoureteral reflux receiving continuous antibiotic prophylaxis.

To investigate the risk factors for new renal scarring (NRS) in children with vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). This was a single-center cohort study. The clinical data of 140 children with grade I-V VUR receiving CAP were analyzed. In this study, exposure variables were sex, younger age at the initial diagnosis of UTI ≤ 12 months, the occurrence of breakthrough urinary tract infection (BT-UTI), high-grade VUR, bilateral VUR, etiology, presence of renal scarring at the initial diagnosis and ultrasound abnormalities. The outcome was NRS. A total of 140 children were included in the risk factor analysis of NRS, 73 of whom experienced NRS, an incidence rate of 52.14%. Multivariate Cox regression suggested that the presence of renal function impairment after the initial diagnosis of UTI (OR 3.411, 95% CI 1.5751-6.646) and the occurrence of BT-UTI while receiving CAP (OR 1.995, 95% CI 1.089-2.958) were independent risk factors for NRS. Multivariate Cox regression showed that high-grade VUR had no significant effects on NRS (OR 0.940, 95% CI 0.462-1.912, P = 0.864). No significant difference was identified in multivariate Cox regression analysis in the IV-V group (vs I-III group) (OR 0.960, 95% CI 0.565-1.633, P = 0.960). Renal function impairment after the initial diagnosis of UTI and the occurrence of BT-UTI while receiving CAP were independent risk factors for NRS. Neither univariate analysis nor multivariate analysis found a correlation between VUR grade and NRS.