Effect and safety of repeated trigone-including intradetrusor BTX-A injection with intermittent catheterization for male adults with NDO and urinary incontinence secondary to spinal cord injury / 中华泌尿外科杂志

Objective:To assess the clinical result of repeated combined detrusor-trigone botulinum toxin A(BTX-A)injection and intermittent catheterization(IC) for male adults with neurogenic detrusor overactivity (NDO) and urinary incontinence(UI) secondary to spinal cord injury(SCI).Methods:From January to August 2021, the data of 43 adult male patients with NDO and UI secondary to SCI who received repeated trigone-including intradetrusor BTX-A injection in Guangdong Provincial Work Injury Rehabilitation Hospital were retrospectively analyzed. The mean age of the patients was (29.1±10.7) years. The mean incontinence specific quality of life (I-QOL) was (39±4.8). The UI episodes was (11.9±2.6), mean voiding volume was (170.7±20.1)ml, mean maximum detrusor pressure at first NDO was (81.4±19.6) cmH 2O and mean volume at first NDO was (169.1±40.0)ml.All patients received trigone-including intradetrusor BTX-A (300 U, 30 sites) injection for four times and IC. Clinical data including I-QOL, bladder diary, video-urodynamic test and adverse events were recorded at baseline and 12 weeks after each injection. Results:Mean interval between four injections were (220.6±27.4), (222.8±24.1) and (224.4±39.0) d ( P=0.13). Compared with baseline data before first injection, mean I-QOL after the first, second, third and fourth injection increased to (54.9±9.1), (56.1±7.9), (61.7±9.1) and (68.8±8.9) (all P<0.001). The number of urinary incontinence cases decreased to 36, 35, 35 and 33 (all P<0.05). The mean urinary incontinence episodes per day decreased to (4.4±0.6), (3.8±0.4), (2.2±0.5) and (2.1±0.3)(all P<0.001). Mean voiding volume increased to (288.3±40.2), (300.0±38.6), (316.9±46.8) and (319.5±36.7) ml (all P<0.001). Mean maximum detrusor pressure at first NDO decreased to (29.4± 11.0), (26.1±8.7), (20.3±5.9) and (18.5±6.0) cmH 2O (all P<0.001) and mean volume at first NDO increased to (270.0±48.7), (284.9±51.3), (287.7±47.9) and (303.0±46.2) ml (all P<0.001), respectively. Compared with four injections, no difference in response was found in the mean I-QOL, the number of urinary incontinence cases, mean urinary incontinence episodes mean voiding volume, mean maximum detrusor pressure at first NDO and mean volume at first NDO (all P>0.05). No de novo VUR occurred and 2 cases of grade Ⅱ VUR at baseline had resolved after the first injection. 9 patients experienced serious gross hematuria within first week after injection, but the urine returned to clear by prolonging the catheter indwelling time or bladder irrigation. 12 patients with active urinary tract infection were treated with indwelling catheter and sensitive antibiotics. Patients continued IC when the symptoms, signs and laboratory examination were normal. Conclusions:Combined detrusor-trigone BTX-A injection and IC could help decrease detrusor pressure, restore some of the lower urinary tract function and improve the quality of life for male patients with NDO and UI secondary to SCI. Repeated injection is as effective and safe as the first injection.

¿La detección de toxinas de Clostridioides difficile es necesaria cuando se detecta la enzima glutamato deshidrogenasa? / Is Clostridioides difficile toxins detection necessary when the glutamate dehydrogenase enzyme is detected?

Resumen Introducción: Clostridioides difficile causa diarrea y colitis pseudomembranosa. Su diagnóstico se realiza con la detección de glutamato-deshidrogenasa (GDH) o las toxinas A y B y se confirma con pruebas de amplificación de ácidos nucleicos. Objetivo: Definir si la determinación de GDH es redundante a la de las toxinas. Métodos: Estudio observacional retrospectivo de muestras fecales de pacientes con sospecha de infección por Clostridioides difficile. Las toxinas y GDH se determinaron mediante inmunocromatografía. Se realizó una simulación bayesiana con los cocientes de probabilidad; se consideró significativo un valor de p < 0.05. Resultados: Se analizaron 329 resultados de GDH y toxinas A y B. Se encontró una prevalencia de infección de Clostridioides difficile de 18.2 %. La sensibilidad y especificidad de la prueba de GDH fue de 0.90 y 0.89, respectivamente. El cociente de probabilidad positivo fue de 8.9 y el negativo, de 0.11. Conclusiones: Un resultado negativo de GDH disminuye considerablemente la probabilidad de infección, pero no la descarta. La detección de toxinas de Clostridioides difficile puede ser necesaria en instituciones donde la amplificación de ácidos nucleicos no es económica o accesible.

Abstract Introduction: Clostridioides difficile causes diarrhea and pseudomembranous colitis. Its diagnosis is made with glutamate dehydrogenase (GDH) or toxins A and B detection and is confirmed with nucleic acid amplification tests. Objective: To define if GDH determination is redundant to that of toxins. Methods: Retrospective, observational study in diarrheal stools of patients with suspected Clostridioides difficile infection. Toxins and GDH were determined by immunochromatography. Bayesian simulation was performed with likelihood ratios; a p-value < 0.05 was regarded as significant. Results: 329 GDH and toxin A and B results were analyzed. Clostridioides difficile infection prevalence was 18.2 %. Sensitivity and specificity of the GDH test were 0.90 and 0.89, respectively. Positive likelihood ratio was 8.9, and negative was 0.11. Conclusions: A negative GDH result considerably reduces the probability of infection but does not rule it out. Clostridioides difficile toxins detection may be necessary in institutions where nucleic acid amplification is not affordable or accessible.

Efficacy and safety study of Chinese botulinum toxin A 100U in patients with overactive bladder: a prospective, multicenter, double-blind and randomized controlled trial / 中华泌尿外科杂志

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Research progress on mechanism of botulinum toxin A in treatment of pain / 中国药理学通报

Botulinum toxin-A ( botulinum toxin-A, BTX-A) is a double chain polypeptide structure formed by 100 kDa heavy chain and 50 kDa light chain through disulfide bond. The light chain is a kind of protease, which can combine with the fusion protein at the neuromuscular junction to prevent synaptic vesicles from anchoring on cell membrane and release acetylcholine, thus interfering with the transmission of nerve impulses. In recent years, the discussion on the clinical application of BTX-A has been a hot spot. Studies have shown that Botulinum toxin A (BTX-A) can effectively treat pain, exerting the characteristics of sustainable effect without addiction, but the mechanism of action of BTX-A is still controversial. This article reviews the mechanism of BTX-A in peripheral and central nervous system.

Localization of the centers of intramuscular nerve dense regions of the rotator cuff muscles: a guide for botulinum toxin A injection for spasticity accompanied by shoulder pain / Localización de los centros de las regiones densas del nervio intramuscular de los músculos del manguito rotador: una guía para la inyección de toxina botulínica A por espasticidad con dolor de hombro

To accurately localize the centers of intramuscular nerve dense regions (CINDRs) of rotator cuff muscles. Twenty adult cadavers were used. The curves on skin connecting the superior angle of scapula with the acromion, and with the inferior angle of scapula were designed as the horizontal (H) and longitudinal (L) reference lines, respectively. One side of the rotator cuff muscles were removed and subjected to Sihler's staining to show intramuscular nerve dense regions, and the contralateral muscles' CINDRs were labeled with barium sulfate and scanned by computed tomography (to determine body surface projection points (P)). The intersection of the longitudinal line from point P to line H, and that of the horizontal line from point P to line L, were recorded as PH and PL, respectively. The projection of CINDRs on the anterior body surface across the saggital plane was defined as P' and the line connecting P to P' was recorded as Line PP'. Percentage positions of CINDRs of PH and PL on lines H and L, and the depths on line PP' were determined under the Syngo system. Two, four, one, and one CINDRs were identified in supraspinatus, infraspinatus, teres minor, and subscapularis muscles, respectively. The positions of PH of these CINDRs on the H-line are as follows: supraspinatus, 25.43 % and 26.59 %; infraspinatus, 53.85 %, 34.63 %, 35.96 % and 58.17 %; teres minor, 74.50 %; and subscapularis, 20.33 %. The PL on the L-line: supraspinatus, 11.09 % and 14.83 %; infraspinatus, 21.59 %, 27.93 %, 48.55 % and 57.52 %; teres minor, 68.28 %; and subscapularis, 52.82 %. The depth on line PP': supraspinatus, 24.83 % and 25.40 %; infraspinatus, 21.55 %, 16.10 %, 10.01 % and 8.14 %; teres minor, 13.27 %; and subscapularis, 22.88 %. The identification of these CINDRs should provide the optimal target position for injecting botulinum toxin A to treat rotator cuff muscles spasticity accompanied by shoulder pain and to improve the efficiency and efficacy of blocking target localization.

Con el objetivo de localizar con precisión los centros de las regiones densas del nervio intramuscular (CRDNI) de los músculos del manguito rotador, se utilizaron veinte cadáveres adultos. Las curvas en la piel que conectan el ángulo superior de la escápula con el acromion y con el ángulo inferior de la escápula se determinaron como líneas de referencia horizontales (H) y longitudinales (L), respectivamente. Se extrajo de un lado los músculos del manguito rotador y se sometió a la tinción de Sihler para mostrar regiones densas de nervios intramusculares, y los CRDNI de los músculos contralaterales se marcaron con sulfato de bario y se escanearon mediante tomografía computarizada (para determinar los puntos de proyección de la superficie corporal (P)). La intersección de la línea longitudinal desde el punto P a la línea H, y de la línea horizontal desde el punto P a la línea L, se registraron como PH y PL, respectivamente. La proyección de CRDNI en la superficie del cuerpo anterior a través del plano sagital se definió como P 'y la línea que conecta P a P' se registró como Línea PP '. Las posiciones porcentuales de los CRDNI de PH y PL en las líneas H y L, y las profundidades en la línea PP 'se determinaron bajo el sistema Syngo. Se identificaron dos, cuatro, uno y un CINDR en los músculos supraespinoso, infraespinoso, redondo menor y subescapular, respectivamente. Las posiciones de PH de estos CRDNI en la línea H son las siguientes: supraespinoso, 25,43 % y 26.59 %; infraspinatus, 53,85 %, 34,63 %, 35,96 % y 58,17 %; redondo menor, 74,50 %; y subescapular, 20,33 %. El PL en la línea L: supraespinoso, 11.09 % y 14.83 %; infraspinatus, 21,59 %, 27,93 %, 48,55 % y 57,52 %; redondo menor, 68.28 %; y subescapular, 52,82 %. La profundidad en la línea PP ': supraespinoso, 24,83 % y 25,40 %; infraspinatus, 21,55 %, 16,10 %, 10,01 % y 8,14 %; redondo menor, 13.27 %; y subescapularis, 22,88 %. La identificación de estos CRDNI debería proporcionar la posición objetivo óptima para inyectar la toxina botulínica A para tratar la espasticidad de los músculos del manguito rotador acompañada de dolor en el hombro y para mejorar la eficiencia y la eficacia del bloqueo de la localización del objetivo.

Efficacy and Safety of Letibotulinum Toxin A for the Treatment of Essential Blepharospasm

PURPOSE: To evaluate the efficacy and safety of BOTULAX® in subjects with essential blepharospasm.METHODS: In this study, a total of 250 subjects with essential blepharospasm were enrolled at 15 investigational sites and a total of 220 subjects completed the study. The efficacy and safety were evaluated at weeks 4 and 16 after treatment compared with baseline. In total, 240 subjects were enrolled, treated with the investigational product, and evaluable for the primary efficacy assessment at week 4 after treatment; these subjects were included in the intention-to-treat (ITT) population. With the ITT set as the main efficacy set, efficacy assessment included Jankovic rating scale (JRS), functional disability score, investigator evaluation of global response and quality of life. Safety assessment including the incidence of adverse events was also performed.RESULTS: In terms of the primary efficacy endpoint (i.e., change in JRS total score at week 4 after treatment from baseline [ITT set]), mean change indicated a statistically significant reduction (p < 0.0001) and demonstrated the non-inferiority of the test drug to similar drugs. In terms of the secondary efficacy endpoints, mean change in JRS total score at week 16 after treatment and mean change in functional disability score at weeks 4 and 16 after treatment both exhibited a statistically significant reduction compared with baseline (p < 0.0001 for all). Among the 249 subjects treated with the investigational product in this study, 44 (17.67%) experienced 76 treatment emergent adverse events but no serious adverse events were observed.CONCLUSIONS: Based on the study results, BOTULAX® is considered to be an effective and safe treatment for essential blepharospasm.

Botulinum toxin a injection in the prevention of facial trauma or postoperative hypertrophic scar: A systemic review of effectiveness and safety / 中国组织工程研究

BACKGROUND: Facial scars are mainly caused by trauma or surgery, which greatly affect the appearance. Dermatologists and plastic surgeons have tried many ways to change the appearance of scars. Botulinum toxin A injection is widely used in clinical practice for prevention of scars, but the efficacy and safety are not proved. OBJECTIVE: To evaluate the effectiveness and safety of botulinum toxin A injection in the prevention of facial trauma or postoperative hypertrophic scar. METHODS: PubMed, EMbase, the Cochrane library, CNKI, CBM, WanFang, and VIP were searched for randomized controlled trials regarding botulinum toxin A injection in the prevention of facial scars. Manual retrieval was done for supplement of incomplete data. Two doctors were responsible for literature screen and evaluation. Finally, 11 randomized controlled clinical trials were included. The experimental group was injected with botulinum toxin A, and the control group was given saline or nothing. Part of the data was analyzed using Revman 5.3 software for meta-analysis, and the data that could not be analyzed using software were subjected to a descriptive analysis. RESULTS AND CONCLUSION: Eleven randomized controlled trials were included, involving 436 patients with 518 wounds. Meta-analyses showed that Vancouver scar scale score, visual analogue scale score and width of scars in the botulinum toxin A group were significantly better than those in the control group (weighted mean difference (WMD)=-1.61, 95% confidence interval (CI)=-2.06 to -0.26, P = 0.02; WMD=1.7, 95%CI=0.38 to 3.02, P = 0.01; WMD=-0.17, 95%CI=-0.22 to -0.12, P < 0.000 1). Incidence of adverse reactions of botulinum toxin A group was higher than that in the control group (χ2 =8.335, P=0.004), but they were all slight and easy to release. There were no serious adverse events in both groups. It seems that botulinum toxin A injection can reduce the width of scars, improve Vancouver scale and visual analogue scale scores. However, it is suggested to make clear communication before and after the operation and take measures to deal with various adverse reactions in advance.

Comparison of two methods for establishing rat dry eye model: lacrimal gland extirpation and lacrimal gland injection of botulinum toxin A / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:The dry eye model of rat was induced either by lacrimal gland extirpation or injection of botulinum toxin A into lacrimal gland. The clinical manifestations, pathological features and cytokine changes of these two models were compared, then we discussed their advantages, disadvantages and applicable scope.<p>METHODS:Thirty healthy 8-week-old male Brown Norway rats were randomly assigned into three groups equally. The left eye of group A was blank group, group B was the left lacrimal gland extirpation model, the left tear gland of group C was injected with botulinum toxin A. We compared the data of Schirmer I test, tear break-up time(BUT), and the corneal fluoresceince staining scores at different times(1d before experiment, 3d, 7d, 14d, 28d, and 42d after the surgical process). We observed pathological changes of conjunctiva, cornea and lacrimal gland at 42d, and we used real-time polymerase chain reaction to analyze interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and epithelial growth factor(EGF).<p>RESULTS:At the 3d, compared with group A, the tear secretion of both group B and group C were continuous decrease(<i>P</i><0.05). At the 7d, compared with group A, the BUT of both group B and group C began to decreased(<i>P</i><0.05), and the corneal epithelial staining scores of both group B and group C began to significantly increase(<i>P</i><0.05). There was no statistical difference in the above clinical data between group B and group C(<i>P></i>0.05). The corneal epithelial cells in group A was set as normal morphology, while the corneal epithelial cells in group B and group C showed filamentous separation of surface cells to varying degrees, and the number of conjunctival goblet cells was decreased. The lacrimal gland of group C was obviously atrophic. In conjunctival and corneal tissues, the expression of EGF, TNF-α and IL-6 were significantly increased in group B and group C, which was statistically significant compared with group A(<i>P</i><0.05). The expression of EGF and TNF-α didn't altered significantly between group B and group C(<i>P</i>>0.05), however, the expression of IL-6 in group B was much higher than that in group C(<i>P</i><0.05).<p>CONCLUSION:In this study, we proved that both lacrimal gland extirpation and lacrimal gland injection botulinum toxin A could construct a stable aqueous tear deficiency dry eye rat model. The appropriate animal model should be selected according to the experimental design and research purpose.

Botulinum toxin A in the early treatment of sixth nerve palsy in type 2 diabetes

Purpose: Our study aims at evaluating the efficacy and safety of botulinum toxin A in the early treatment of sixth nerve palsy in type 2 diabetic patients. Methods: This study is a prospective and interventional clinical case series of patients presenting with acute onset of sixth cranial nerve palsy, who received injection botulinum toxin A. Results: Thirty-one cases were included in the study. 58% of the study subjects had incomplete palsy at presentation (abduction deficit -1 to -3) and 42% had complete palsy (-4 and -5). The median dosage of injection was 5 U (range 3--6 U). The median follow-up period is 2 months. The P value shows that there is statistically significant improvement in head turn, ocular deviation in primary position, and improvement in abduction between baseline and 1 week (P-value <0.001), 1 month (P-value <0.001) and 2 month (P-value <0.001) postinjection follow-up visits. 90.3% of patients had full resolution of symptoms in the last follow-up visit. 83.9% of patients were successfully treated. Conclusion: Early injection of botulinum toxin A in select patients with acquired sixth nerve palsy due to diabetes is a safe and efficient treatment option in alleviating symptoms, restoring function and quality of life and reducing need for surgical interventions in future.

Molecular characterization of virulence genes cctA, nanA, and fliC in Clostridium chauvoei from Rio Grande do Sul and São Paulo State, Brazil / Caracterização molecular dos genes de virulência cctA, nanA e fliC em Clostridium chauvoei isolados no Rio Grande do Sul e São Paulo, Brasil

ABSTRACT: Clostridium chauvoei toxin A (CctA), neuraminidase (NanA), and flagellin (FliC) proteins contribute to the pathogenicity of Clostridium chauvoei, the causative agent of blackleg in cattle. The aim of this study was to analyze the genetic variability of cctA, nanA, and fliC genes in C. chauvoei isolates from the Rio Grande do Sul and São Paulo state- Brazil, during different sampling periods. The presence of these genes was verified through PCR amplification and partial gene sequencing of 17 strains. Alignment of PCR amplicons combined with bioinformatics analysis was used in an attempt to study the variability across C. chauvoei solates. The similarity among the partial sequences of cctA and nanA genes was 100%. The sequencing of fliC revealed three different paralog alleles of flagellin, and two strains were seen to be polymorphic, with amino acid alterations in the predicted protein. Overall, this study indicates that strains of C. chauvoei isolated in Brazil are highly conserved with respect to the virulence factors evaluated.

RESUMO: Toxina A de Clostridium chauvoei (CctA), neuraminidase (NanA) e flagelina (FliC) são proteínas que contribuem para a patogenicidade de Clostridium chauvoei, o agente causador do carbúnculo sintomático em bovinos. O objetivo deste estudo foi analisar a variabilidade genética dos genes cctA, nanA, e fliC em C. chauvoei isolados em diferentes períodos no Rio Grande do Sul e São Paulo. A presença destes genes foi verificada pela amplificação dos produtos da PCR e sequenciamento parcial dos genes de 17 cepas. Os alinhamentos da amplificação dos produtos da PCR combinados com a análise de bioinformática foram utilizados na tentativa de avaliar a variabilidade dos genes entre os isolados de C. chauvoei. A similaridade do sequenciamento parcial dos genes cctA e nanA foi 100%. O sequenciamento do fliC revelou três alelos paralogos diferentes de flagelina e duas cepas mostraram polimorfismos, causando alterações na sequência de aminoácidos. As cepas de C. chauvoei isoladas no Brasil mostraram-se altamente conservadas em relação aos fatores de virulência avaliados neste estudo.

Outcomes of Intradetrusor Onabotulinum Toxin A Therapy in Overactive Bladder Refractory to Sacral Neuromodulation / 대한배뇨장애요실금학회지

PURPOSE: Intradetrusor onabotulinum toxin A (BTXA) and sacral neuromodulation (SNM) are effective third-line therapies for overactive bladder (OAB). We aimed to measure the outcomes of BTXA for treatment of OAB refractory to initial SNM and identify patient characteristics associated with these outcomes. METHODS: This retrospective cohort study included patients who failed to respond to initial SNM treatment for OAB and subsequently received BTXA at a single provider’s clinic between January 2013 and December 2016. Treatment successes were defined as patients willing to continue BTXA or who found symptom relief whereas treatment failures discontinued BTXA due to adverse effects or lack of symptom relief. Symptoms and patient-reported outcomes on validated questionnaires were compared before the initial BTXA trial to 2 months after the last BTXA treatment. The SNM failure BTXA groups were also compared to BTXA SNM naïve groups. RESULTS: Of 18 patients who received BTXA after failed SNM treatment, 7 (39%) achieved treatment success. Successfully treated patients demonstrated decreased urinary frequency from a median 11 voids/day pre-BTXA to 8 voids/day with BTXA (P=0.042). Patients whose treatment failed reported increased complaints of a weak urinary stream (P=0.03) and higher frequency of straining to urinate (P=0.016) than the successful treatment group pre-BTXA. Compared to BTXA patients without prior SNM, the odds of failing BTXA after initial SNM were 3.6 times higher (P=0.016). CONCLUSIONS: BTXA appears effective for OAB refractory to SNM, although the success rate is lower compared to BTXA patients without SNM exposure.

Effect and safety of botulinum toxin A injection in external urethral sphincter for male patients with neurogenic detrusor underactivity / 中华泌尿外科杂志

Objective@#To assess clinical effect and safety of botulinum toxin A injection in external urethral sphincter for male patient with neurogenic detrusor underactivity(DU).@*Methods@#A prospective and self-controlled trail was conducted from August 2012 to October 2017. Male patients with nerve injury, dysuria more than 6 months, DU(bladder contractility index less than 100) were enrolled in this study. Exclusion criteria included patients with acute urinary tract infection, bladder stone, benign prostate hyperplasia, urethral stricture and urethral diverticulum.100 IU BTX-A was dissolved in 4ml normal saline, and the solution of BTX- A was injected into 4 different points(3-o’clock, 6-o’clock, 9-o’clock, and 12-o’clock) in external urinary sphincter with each point of 1ml solution. Patients were evaluated at baseline and 12 weeks after injection. The outcomes included post void residual (PVR), maximum flow rate (Qmax), maximum detrusor pressure during voiding phases (Pdet.max), maximum urethral closure pressure (MUCP), the case number of intermittent catheterization (IC)and the score of quality of life (QOL score). Adverse events were also recorded.@*Results@#A total of 58 male patients (all from Guangdong provincial work injury rehabilitation hospital)with mean age 28.6 years suffered from cerebral palsy (n=2), cerebrovascular accident(n=19)and spinal cord injury(n=37) were included into the study. Compared to baseline data, significant difference were observed at week 12 in PVR (56.68 ml vs. 280.11 ml, P<0.001), Pdet.max(23.95 cmH2O vs. 30.01 cmH2O, P=0.019), Qmax(6.74 ml/s vs. 3.28 ml/s, P=0.042), MUCP(48.25 cmH2O vs. 79.34 cmH2O, P<0.001), the case number of IC(40 vs. 58, P<0.001) and QOL score(3.63 vs.5.22, P<0.001) respectively. 5 cases developed perineal pain and 16 cases developed mild transient haematuria. These adverse events were disappeared by medical symptomatic treatment during 3-5 days.@*Conclusions@#BTX-A externalurethral sphincter injections help reduce urethra resistance and also improve the quality of life for patients with neurogenic detrusor underactivity.

Helicobacter pylori virulence factor vacuolating cytotoxin A ( VacA) promotes homologous recombi-nation repair in GES-1 cells / 中华微生物学和免疫学杂志

Objective To analyze the impact of Helicobacter pylori standard strain (Hp P12) and its virulence factor vacuolating cytotoxin A ( VacA) on DNA damage and homologous recombination ( HR) repair in a human gastric epithelial cell line (GES-1). Methods Strains of Hp P12 and vacA gene knock-out Hp P12 ( Hp P12 ΔvacA) were respectively used to infect GES-1 cells at a multiplicity of infection of 100. GES-1 cells treated with etoposide (50μmol/L) or mitomycin (0. 5μg/ml) for 2 h were used as posi-tive control. Western blot and immunofluorescence were performed to detect the expression of DNA damage marker protein γH2AX and key HR repair proteins (Rad51, pMRE11, CtIP and pCtIP) and the recruitment of them at DNA damage sites. Human embryonic kidney HEK-293 ( DR-GFP) cells were infected with Hp P12 and Hp P12 ΔvacA strains to verify the impact of VacA on HR repair efficiency. Results The expres-sion and recruitment of γH2AX and key HR repair proteins ( Rad51, pMRE11, CtIP and pCtIP) were in-creased in Hp P12-infected cells as compared with that in uninfected and Hp P12 ΔvacA-infected cells ( all P<0. 05). To evaluate the HR repair efficiency, I-SceⅠ plasmid-transfected HEK-293 (DR-GFP) cells were infected with Hp P12 and Hp P12 ΔvacA and the results showed that green fluorescent protein ( GFP)-positive cells were decreased after infection, especially in Hp P12 ΔvacA-infected cells (both P<0. 05). Conclusions Hp P12 infection could cause DNA damage and promote HR repair in GES-1 cells, in which the virulence factor VacA played an important role.

Botulinum toxin type A injection in the treatment of dystonia after a stroke / 中华物理医学与康复杂志

Objective To observe the effect of injecting botulinum toxin type A on muscle tension,disability level and ability in the activities of daily living in patients with post-stroke dystonia.Methods Thirty-two patients with post-stroke dystonia were divided into an observation group (n =16) and a control group (n =15).The patients in the observation group were injected with 200-600 U of botulinum toxin type A in the relevant muscles,while the patients in the control group were given 12 mg diphenhydrazole hydrochloride tablets orally.Before and 2,6 and 12 weeks after the treatment,spasticity,disability and daily living ability were evaluated in both groups using the modified Ashworth scale (MAS),a disability assessment scale (DAS) and the modified Barthel index (MBI).Results After the treatment,the average MAS,DAS and MBI scores of both groups were significantly better than before the treatment.And the average MAS,DAS and MBI scores of the observation group were significantly better than those of the control group.Conclusion Botulinum toxin A injection can significantly improve dystonia and relieve disability among stroke survivors.

Simultaneous Detection of Clostridioides difficile Glutamate Dehydrogenase and Toxin A/B: Comparison of the C. DIFF QUIK CHEK COMPLETE and RIDASCREEN Assays

Various commercial assays have recently been developed for detecting glutamate dehydrogenase (GDH) and/or toxin A/B to diagnose Clostridioides difficile infection (CDI). We compared the performance of two assays for the simultaneous detection of C. difficile GDH and toxin A/B, using 150 stool samples: C. DIFF QUIK CHEK COMPLETE (QCC; TechLab, Blacksburg, VA, USA) and RIDASCREEN Clostridium difficile GDH (RC-GDH) and Toxin A/B (RC-Toxin A/B; R-Biopharm, Darmstadt, Germany). For GDH detection, QCC and RC-GDH showed satisfactory sensitivity (95.7% and 94.3%, respectively) and specificity (92.5% and 93.8%, respectively) compared with C. difficile culture. For toxin A/B detection, QCC showed higher sensitivity than RC-Toxin A/B (60.0% vs 33.3%, P < 0.001) compared with toxigenic C. difficile culture. When the results of QCC or RC-GDH+RC-Toxin A/B were used as the first step of a two-step algorithm for diagnosing CDI, QCC permitted more accurate discrimination than RC of positive or negative results for CDI (77.3% and 65.3%, respectively). QCC is useful for the simultaneous detection of C. difficile GDH and toxin A/B as a part of the two-step algorithm for diagnosing CDI.

Advance of Botulinum Toxin A in Neurological Disorders (review) / 中国康复理论与实践

The studies of Botulinum toxin A (BoNT/A) are progressing in many fields. BoNT/A has been used in neurological disorders, such as pains, spasticity, dystonias and autonomic disorders, etc. The pharmacological interaction among BoNT/A, neuronal transport and protein has been explored, and promoted basic science studies.

A pilot study comparing the clinical efficacy of freshly reconstituted and botulinum toxin a reconstituted 1, 2 and 3 months before application in the treatment of axillary hyperhidrosis

BACKGROUND@#Most manufacturers of commercially available botulinum toxin A (BTX-A) recommend that the vials should be used within 24 hours after reconstitution to ensure efficacy, which in some instances would mean wastage of remaining reconstituted solution. Several studies have evaluated the efficacy of stored reconstituted BTX-A and have concluded that the use of BTX-A reconstituted and refrigerated for up to 6 weeks prior to administration does not significantly alter its efficacy in the treatment of facial rhytides.@*OBJECTIVES@#Our study aimed to compare the clinical efficacy and safety of freshly reconstituted BTX-A and BTX-A reconstituted 1, 2 or 3 months prior to administration in the treatment of axillary hyperhidrosis.@*METHODOLOGY@#Patients with primary axillary hyperhidrosis were enrolled in this pilot study. Freshly reconstituted BTX-A and BTX-A reconstituted 1, 2 and 3 months prior were administered in 4 pre-determined areas in the same patient. The degree of hyperhidrosis was assessed subjectively using Hyperhidrosis Disease Severity Scale (HDSS) and objectively using Minor’s iodine starch test followed by Sweating Intensity Visual Scale (SIVS) at 0, 2, 6 and 12 weeks after administration.@*RESULTS@#Five patients were enrolled in the study. Kruskall-Wallis test showed that HDSS at baseline was significantly different from follow-up periods with noted improvement from baseline to 2 weeks follow-up. Using Kruskall-Wallis test, SIVS was found to be not significantly different among these 4 treatment areas. In addition, significantly improved SIVS scores were noted as early as 2 weeks after administration in all 4 areas of treatments. There were no noted adverse effects in all patients at baseline and at all follow-up visits.@*CONCLUSION@#The clinical efficacy and safety of BTX-A reconstituted 1, 2 and 3 months prior to administration is comparable to that of freshly reconstituted BTX-A in the treatment of axillary hyperhidrosis.

Effect and safety of botulinum toxin A injection in external urethral sphincter for male patients with neurogenic detrusor underactivity / 中华泌尿外科杂志

Objective To assess clinical effect and safety of botulinum toxin A injection in external urethral sphincter for male patient with neurogenic detrusor underactivity (DU).Methods A prospective and self-controlled trail was conducted from August 2012 to October 2017.Male patients with nerve injury,dysuria more than 6 months,DU (bladder contractility index less than 100) were enrolled in this study.Exclusion criteria included patients with acute urinary tract infection,bladder stone,benign prostate hyperplasia,urethral stricture and urethral diverticulum.100 IU BTX-A was dissolved in 4ml normal saline,and the solution of BTX-A was injected into 4 different points(3-o'clock,6-o'clock,9-o'clock,and 12-o'clock) in external urinary sphincter with each point of 1ml solution.Patients were evaluated at baseline and 12 weeks after injection.The outcomes included post void residual (PVR),maximum flow rate (Qmax),maximum detrusor pressure during voiding phases (Pdet.max),maximum urethral closure pressure (MUCP),the case number of intermittent catheterization (IC) and the score of quality of life (QOL score).Adverse events were also recorded.Results A total of 58 male patients (all from Guangdong provincial work injury rehabilitation hospital) with mean age 28.6 years suffered from cerebral palsy (n =2),cerebrovascular accident(n =19)and spinal cord injury(n =37) were included into the study.Compared to baseline data,significant difference were observed at week 12 in PVR (56.68 ml vs.280.11 ml,P ＜ 0.001),Pdet.max (23.95 cmH2O vs.30.01 cmH2O,P =0.019),Qmax(6.74 ml/s vs.3.28 ml/s,P =0.042),MUCP(48.25 cmH2O vs.79.34 cmH2O,P ＜0.001),the case number of IC(40 vs.58,P ＜0.001) and QOL score(3.63 vs.5.22,P ＜ 0.001) respectively.5 cases developed perineal pain and 16 cases developed mild transient haematuria.These adverse events were disappeared by medical symptomatic treatment during 3-5 days.Conclusions BTX-A externalurethral sphincter injections help reduce urethra resistance and also improve the quality of life for patients with neurogenic detrusor underactivity.

Effect of the masseter muscle injection of botulinum toxin A on the mandibular bone growth of developmental rats / 대한악안면성형재건외과학회지

BACKGROUND: The objective of this study was to evaluate the influence of masticatory muscle injection of botulinum toxin type A (BTX-A) on the growth of the mandibular bone in vivo. METHODS: Eleven Sprague-Dawley rats were used, and BTX-A (n = 6) or saline (n = 5) was injected at 13 days of age. All injections were given to the right masseter muscle, and the BTX-A dose was 0.5 units. All of the rats were euthanized at 60 days of age. The skulls of the rats were separated and fixed with 10% formalin for micro-computed tomography (micro-CT) analysis. RESULTS: The anthropometric analysis found that the ramus heights and bigonial widths of the BTX-A-injected group were significantly smaller than those of the saline-injected group (P < 0.05), and the mandibular plane angle of the BTX-A-injected group was significantly greater than in the saline-injected group (P < 0.001). In the BTX-A-injected group, the ramus heights II and III and the mandibular plane angles I and II showed significant differences between the injected and non-injected sides (P < 0.05). The BTX-A-injected side of the mandible in the masseter group showed significantly lower mandibular bone growth compared with the non-injected side. CONCLUSION: BTX-A injection into the masseter muscle influences mandibular bone growth.

Local Injections of Botulinum Toxin A in Treatment of Androgenetic Alopecia / 中山大学学报(医学科学版)

[Objective] To determine the efficacy and safety of local injections of botulinum toxin A in the treatment of androgenetic alopecia.[Methods] 72 male patients were randomly into botulinum toxin An group (n=35) and the control group (n=37),the treatment time was 6 months.All the patients were photographed and evaluated,before the treatment,and 3 months and 6 months.[Results] After the treatment of half a year,a good result was observed,the hair density in the treatment group was higher after 3months and 6 months than before the treatment (P＜0.05),but there was no difference between the after 3months and 6 months (P＞0.05),the hair density in the control group was higher after 6 months than before the treatment and after 3 months (P＜0.05),but there was no difference between the after 3 months and before the treatment (P＞0.05);but there was no difference between the after 3 months and 6 months (P＞0.05);After 6 months,the effective ratio and in two group were 91.4％ and 86.5％ in treated group,it showed no significant difference (P＞0.05) [Conclusion] the treatment of local injections of botulinum toxin A has a marked effect on androgenetic alopecia,it is safe and effective.