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Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.

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Colecistectomía , Neoplasias de la Vesícula Biliar , Análisis de Series de Tiempo Interrumpido , Humanos , Chile/epidemiología , Colecistectomía/estadística & datos numéricos , Colecistectomía/métodos , Femenino , Persona de Mediana Edad , Masculino , Adulto , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias del Sistema Digestivo/cirugía , Neoplasias del Sistema Digestivo/mortalidad , Anciano , Análisis de Datos

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Introducción: El cateterismo urinario es un procedimiento frecuente y en ocasiones es utilizado por fuera de las indicaciones aceptadas para el mismo. Esto aumenta el riesgo de complicaciones vinculadas a su uso, por lo que pueden ser prevenibles. El objetivo del estudio es conocer las características del uso de cateterismo urinario en pacientes ingresados en salas de cuidados moderados de un hospital universitario del tercer nivel de atención, determinar la frecuencia, duración e indicaciones más frecuentes, así como evaluar la presencia de complicaciones asociadas al mismo Metodología: Estudio de corte transversal, realizado en salas de cuidados moderados de un hospital terciario y universitario de Montevideo, Uruguay, el 21 de diciembre de 2022. Se incluyeron pacientes hospitalizados que presentaban o presentaron catéter vesical en la presente internación y se completó la recolección de variables mediante la revisión de la historia clínica. Resultados: De 155 pacientes ingresados en salas de cuidados moderados, a 26 (16,7%) les fue colocado un catéter urinario. La mediana de edad fue 61 años, 80% eran de sexo masculino. La mediana de internación fue de 22 días. En todos los pacientes se utilizó sonda vesical y el 54% fue colocado en el Departamento de Emergencia. En el 46% de los pacientes no se encontró indicación escrita de colocación en la historia clínica. En 50% de los casos no está especificado el motivo de indicación de sonda vesical, mientras que las indicaciones identificadas más frecuentes fueron el control de diuresis (27%) y la desobstrucción de vía urinaria baja (23%). La duración de cateterismo fue de una mediana de 13,5 días, mientras que el 27% de los pacientes la usaron más de 30 días. 35% de los pacientes presentaron complicaciones vinculadas a la sonda vesical, en su mayoría no infecciosas (27%) y 15% presentaron infección urinaria. Estos pacientes tuvieron una duración de cateterismo mayor a los que no presentaron complicaciones (23 vs 10 días, p=0,411). Conclusiones: El catéter vesical fue utilizado en un porcentaje no despreciable de pacientes ingresados en salas de cuidados moderados, de forma prolongada y frecuentemente sin indicación precisa, lo cual expone a un riesgo aumentado de complicaciones vinculadas.

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Introduction: Urinary catheterization is a frequent procedure and is sometimes used outside of its accepted indications. This increases the risk of complications related to its use, so they may be preventable. The objective of this study is to know the characteristics of the use of urinary catheterization in patients admitted to moderate care wards of a tertiary care university hospital, to determine the frequency, duration and most frequent indications, as well as to evaluate the presence of associated complications. Methodology: Cross-sectional study, carried out in moderate care wards of a tertiary care and university hospital in Montevideo, Uruguay, on December 21, 2022. Hospitalized patients who present or presented a bladder catheter during the present hospitalization were included, and the collection of variables was completed by reviewing the medical history. Results: Of 155 patients admitted to moderate care wards, 26 (16.7%) had a urinary catheter placed. The median age was 61 years, 80% were male. The median hospitalization was 22 days. In all patients a bladder catheter was used and 54% were placed in the Emergency Department. In 46% of the patients, no written indication for placement was found in the clinical history. In 50% of cases, the reason for indicating the bladder catheter is not specified, while the most frequent indications identified were diuresis control (27%) and lower urinary tract obstruction (23%). The duration of catheterization was a median of 13.5 days, while 27% of the patients used it for more than 30 days. 35% of the patients presented complications related to the bladder catheter, mostly non-infectious (27%) and 15% presented urinary tract infection. These patients had a longer duration of catheterization than those without complications (23 vs 10 days, p=0,411). Conclusions: The bladder catheter was used in a non-negligible percentage of patients admitted to moderate care wards, for a long time and often without a precise indication, which exposes them to an increased risk of related complications.

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Introdução: O cateterismo urinário é um procedimento frequente e às vezes é usado fora de suas indicações aceitas. Isso aumenta o risco de complicações relacionadas ao seu uso, portanto, podem ser evitáveis. O objetivo deste estudo é conhecer as características do uso do cateterismo urinário em pacientes internados em enfermarias de cuidados moderados de um hospital universitário terciário, determinar a frequência, duração e indicações mais frequentes, bem como avaliar a presença de complicações associadas ao mesmo. Metodologia: Estudo transversal, realizado em quartos de cuidados moderados de um hospital terciário e universitário em Montevidéu, Uruguai, em 21 de dezembro de 2022. Foram incluídos pacientes que apresentaram ou apresentaram sonda vesical durante a internação atual e a coleta de variáveis ​​foi concluída .revisando o histórico médico. Resultados: Dos 155 pacientes admitidos em enfermarias de cuidados moderados, 26 (16,7%) tiveram um cateter urinário colocado. A idade média foi de 61 anos, 80% eram do sexo masculino. A mediana de internação foi de 22 dias. Em todos os doentes foi utilizada sonda vesical e 54% foram internados no Serviço de Urgência. Em 46% dos pacientes, nenhuma indicação escrita para colocação foi encontrada na história clínica. Em 50% dos casos não é especificado o motivo da indicação da sonda vesical, enquanto as indicações mais frequentes identificadas foram controle da diurese (27%) e desobstrução do trato urinário inferior (23%). A duração do cateterismo foi em média de 13,5 dias, enquanto 27% dos pacientes o utilizaram por mais de 30 dias. 35% dos pacientes apresentaram complicações relacionadas ao cateter vesical, em sua maioria não infecciosas (27%) e 15% apresentaram infecção urinária. Esses pacientes tiveram uma duração mais longa de cateterismo do que aqueles sem complicações (23 vs 10 dias, p=0,411). Conclusões: A sonda vesical foi utilizada em percentual não desprezível de pacientes internados em quartos de cuidados moderados, por tempo prolongado e muitas vezes sem indicação precisa, o que os expõe a um risco aumentado de complicações associadas.

RESUMEN

BACKGROUND: Urinary tract infections are prevalent among children and are responsible for a significant healthcare burden. Antibiotic therapy is the cornerstone of treatment, but the optimal treatment duration remains elusive. OBJECTIVES: This systematic review and meta-analysis aimed to explore the optimal duration of antibiotic therapy for urinary tract infection (UTI) in pediatric patients. DATA SOURCES: A comprehensive search was performed, including MEDLINE, Embase, and Cochrane Library databases. STUDY ELIGIBILITY CRITERIA: We included only randomized controlled trials (RCTs) comparing short-course (2 to 5 days) and standard-course (≥ 7 days) antibiotic treatment in patients < 18 years of age. STUDY APPRAISAL AND SYNTHESIS METHODS: We performed this systematic review and meta-analysis following Cochrane Collaboration recommendations using a random-effects model. Effect estimate was calculated using the risk ratio (RR) with 95% confidence interval (95% CI) for dichotomous and mean difference (MD) with 95% CI for continuous endpoints. Significance was regarded at p-value < 0.05. Statistical analysis was performed using Review Manager 5.4.1. RESULTS: Data from 12 RCTs, encompassing 1442 children, were included. Follow-up ranged from 1 to 12 months. The mean age was 5.9 years, with approximately 87% female patients. E. coli was the most common pathogen isolated from urine cultures. There was a significant difference in cure rates (RR 0.97; 95% CI 0.95-0.99; p = 0.01) between the groups when only studies that included febrile UTI were analyzed together, favoring 7 days or more of treatment, but with high heterogeneity. Otherwise, there was no significant difference in cure rates (RR 0.99; 95% CI 0.91-1.08; p = 0.80) in children with afebrile UTI or recurrence of UTI at any time in children with afebrile (RR 0.98; 95% CI 0.84-1.15; p = 0.80) or febrile UTI (RR 0.52; 95% CI 0.10-2.83; p = 0.45). Also, there was no significant difference in failure rates in children with urinary tract abnormalities and afebrile UTI (RR 0.79; 95% CI 0.47-1.32; p = 0.36), between the short- and the standard-course treatment groups. LIMITATIONS: This analysis was limited by the moderate heterogeneity and the small subgroup of children with urinary tract abnormalities, which could have underpowered our results. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The primary outcome of this analysis suggests that a short course of antibiotic therapy is feasible in children with afebrile UTI, but more studies are warranted to safely establish an optimal treatment duration for children with febrile UTI. SYSTEMATIC REVIEW REGISTRATION NUMBER: The study protocol was registered in the PROSPERO platform under the number CRD42023489094.

RESUMEN

BACKGROUND: Uroflowmetry is a non-invasive examination considered as a first-line assessment for children with lower urinary tract symptoms (LUTS). Currently, the performance of two uroflowmetry tests is recommended by ICCS for all patients with LUTS. This study aims to evaluate the differences between two uroflowmetry tests in children with lower urinary tract symptoms and their impact on the patient's diagnostic workup and clinical outcome. METHODS: Forty patients with LUTS, aged 4-17 years, were evaluated prospectively with two consecutive uroflowmetry tests and ultrasonography. They were classified based on the ICCS criteria for curve pattern and divided into two groups based on the SPU classification of fractionated (staccato and intermittent) and smooth (bell, tower and plateau). They were also separated into three groups based on estimated bladder capacity (voided volume + post-void residual on ultrasound): high (>115%), low (<60%) or normal capacity. RESULTS: The mean age was 8 (IQR 6.0-10.0) years and 25 (62.5%) patients were female. There was an increase in nonbell-shaped curves from the first (32.5%) to the second test (52.5%). The curve shape between the uroflowmetries based on ICCS classification showed a Kappa value of 0.349 (fair). Classifying curves as fractionated or smooth yielded a Kappa value of 0.714 (substantial) (table). The Bland-Altman test showed disagreement in the parameter of time to Qmax. There was a significant difference in categorizing bladder capacity as high, low, or normal: it was concordant in 63.6% for high, 68.4% for normal and 50% for low capacity (p = 0.001). DISCUSSION: Despite the disagreement found classifying the curves based on the ICCS pattern, also demonstrated in other studies, there was a substantial agreement using the SPU criteria. It reinforces the greater reliability of the SPU system and it may be the key to reduce the subjectivity of uroflowmetry. Even though this classification being associated with a higher agreement in interpretation of the curves, repeating uroflowmetry does not present a clinically significant divergence that changes the patient's diagnostic workup. Our study is limited by the lack of EMG and larger sample. CONCLUSION: Considering the flow curve pattern, the agreement between two uroflowmetries was substantial according to the SPU and only reasonable by the ICCS classification. Regardless of some differences found between the flows, a second uroflowmetry test might not have clinical relevance that justifies its recommendation for all patients.

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PURPOSE: Recent research has highlighted the mechanotransducer PIEZO2 as a crucial factor in lower urinary tract function, demonstrating associations with bladder compliance (BC), bladder wall thickening, and elevated bladder pressure. We explored the hypothesis that PIEZO2 expression may be associated with lower urinary tract dysfunction in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH). METHODS: The study included a consecutive series of patients undergoing open prostatectomy for BPH at our hospital between September 2014 and January 2016. All participants underwent comprehensive preoperative evaluations, including urodynamic assessments. During prostatectomy, a full-thickness fragment of the bladder wall was obtained for subsequent PIEZO2 gene expression analysis. Cadaveric organ donors served as the control group. RESULTS: PIEZO2 expression was downregulated in the detrusor muscle of men with BPH compared to the control group. Among patients with BPH, those experiencing urinary retention and requiring an indwelling catheter exhibited significantly lower PIEZO2 messenger RNA (mRNA) expression than patients capable of spontaneous voiding. PIEZO2 mRNA expression was similar in men with and without detrusor overactivity. Additionally, a positive correlation was found between PIEZO2 mRNA expression levels and BC. CONCLUSION: Our findings indicate that PIEZO2 is downregulated in the detrusor muscle of men with BPH, particularly in those experiencing urinary retention and those with reduced BC. These results suggest a potential role for PIEZO2 in BOOinduced bladder dysfunction. Further research is required to clarify the role of PIEZO mechanotransducers in the bladder and to explore their therapeutic implications.

RESUMEN

A calyceal diverticulum is a transitional epithelium-lined outpouching of a renal calyx which communicates with the main collecting system through a narrow infundibulum. There are two types of calyceal diverticula: type I, the most common, communicates with the minor calyx, and type II communicates with the major calyx or renal pelvis. Calyceal diverticula are rare and mostly found incidentally; however, they can cause urinary tract infection symptoms (e.g., hematuria, pain, and fever). Diagnosing an infected calyceal diverticulum during pregnancy is particularly challenging due to overlapping symptoms and the limitations of imaging modalities that avoid ionizing radiation. Prompt diagnosis and treatment are necessary to avoid irreversible renal dysfunction and/or urological surgery. Currently, there are no established treatment guidelines for diagnosing and managing infected calyceal diverticula in pregnant patients. The rarity of this condition and the complexities introduced by pregnancy create challenges in standardizing care and determining the optimal treatment strategy, timing of interventions, and the impact on maternal and fetal outcomes. A 29-year-old primigravid woman presented emergently to the hospital at 15 weeks and 4 days gestation with concerns of severe right-sided flank pain and hematuria. Initial renal ultrasound revealed a complex, hypovascular lesion in the interpolar region of the right kidney measuring 6.9 × 6.8 × 3.7 cm, suspicious for mass versus pyelonephritis with associated phlegmon. Further characterization of the lesion by MRI revealed communication between the lesion and the mid-pole collecting system. Differential diagnoses included infected calyceal diverticulum, hydronephrosis of a duplicated system, renal abscess, and infected urinoma. Through a multidisciplinary approach, including ultrasound-guided placement of a drainage catheter at 16 weeks gestation, and tailored intravenous antibiotic therapy, the patient delivered a 3379 g male at 40 weeks and 0 days gestation. This case highlights the potential for conservative management in the absence of clear guidelines and underscores the importance of collaboration among obstetrics, urology, infectious disease, and interventional radiology teams. The implications of this case extend to increasing awareness of calyceal diverticula as a differential diagnosis in pregnant patients presenting with atypical urinary symptoms. It emphasizes the necessity of a multidisciplinary approach to ensure both maternal and fetal safety and offers valuable insights that could inform future cases, contributing to the development of more concrete guidelines for managing infected calyceal diverticula during pregnancy. Consent was obtained from the patient and IRB approval was not required for this case.

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Probiotics, particularly yeasts from the genus Saccharomyces, are valuable for their health benefits and potential as antibiotic alternatives. To be effective, these microorganisms must withstand harsh environmental conditions, necessitating advanced protective technologies such as encapsulation to maintain probiotic viability during processing, storage, and passage through the digestive system. This review and meta-analysis aims to describe and compare methods and agents used for encapsulating Saccharomyces spp., examining operating conditions, yeast origins, and species. It provides an overview of the literature on the health benefits of nutritional yeast consumption. A bibliographic survey was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The meta-analysis compared encapsulation methods regarding their viability after encapsulation and exposure to the gastrointestinal tract. Nineteen studies were selected after applying inclusion/exclusion criteria. Freeze drying was found to be the most efficient for cell survival, while ionic gelation was best for maintaining viability after exposure to the gastrointestinal tract. Consequently, the combination of freeze drying and ionic gelation proved most effective in maintaining high cell viability during encapsulation, storage, and consumption. Research on probiotics for human food and animal feed indicates that combining freeze drying and ionic gelation effectively protects Saccharomyces spp.; however, industrial scalability must be considered. Reports on yeast encapsulation using agro-industrial residues as encapsulants offer promising strategies for preserving potential probiotic yeasts, contributing to the environmental sustainability of industrial processes.

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BACKGROUND: Biliary tract cancers are serious diseases and new biomarkers may be useful for the optimal management and prediction of these cases. This study aimed to evaluate the prognostic significance of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, a novel composite marker, in patients with metastatic biliary tract cancer. METHODS: Patients with biliary tract cancers were analyzed retrospectively. Laboratory values, patient and disease characteristics, and survival rates were evaluated. The diagnostic impact of the HALP score was assessed with regression analyses. RESULTS: The study included 106 individuals with metastatic biliary tract cancer. Based on the median HALP score, ≥ 2.22 was considered a high score and < 2.22 was considered low. The overall average survival time was found to be 11.4 months. Patients with low HALP scores had median overall survival of 9.5 months, while those with high HALP scores had median overall survival of 15.9 months. In multivariate analysis, Eastern Cooperative Oncology Group performance status, CA19-9 level, and HALP score remained significant predictors of overall survival. CONCLUSION: The HALP score appears to be a useful prognostic marker in patients with metastatic biliary tract cancer.

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BACKGROUND: Biliary tract cancer (BTC) is a highly heterogeneous aggressive tumor, and advanced patients have poor prognosis. This work aimed to evaluate the efficacy and safety of camrelizumab combined with chemotherapy in treating advanced BTC, and to explore predictive biomarkers for distinguishing effective population. METHODS: 183 advanced BTC patients admitted from September 2018 to September 2021 were retrospectively selected. 93 patients were treated with camrelizumab combined with chemotherapy (C+C group) and 90 patients were treated with chemotherapy alone (C group). Objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were analyzed between two groups. Peripheral blood lymphocyte subsets were assessed by flow cytometry pre- and post-treatment. RESULTS: The mPFS (6.9 months) and mOS (12.1 months) in the C+C group were significantly longer than those in the C group, which were 5.2 months and 9.8 months respectively (HR 0.46, 95% CI 0.38-0.54, p=0.017; HR 0.39, 95% CI 0.32-0.47, p=0.033). The percentage of Total T, CD4+T, natural killer (NK) cells, lymphocyte, and CD4+/CD8+ cell ratios were significantly increased in effective patients after C+C treatment, but didn't increase in progressive disease (PD) patients. Higher percentage of Total T, CD4+T, and higher CD4+/CD8+ cell ratios post-treatment were associated with longer OS. CONCLUSIONS: Camrelizumab combining chemotherapy significantly prolonged the mPFS and mOS of advanced BTC patients. Immunotherapy may improve the immune status of advanced patients, and immunotherapy efficacy might be predicted based on the peripheral blood lymphocyte subsets.

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Urinary tract infections (UTIs) represent a clinical and epidemiological problem of worldwide impact that affects the economy and the emotional state of the patient. Control of the condition is complicated due to multidrug resistance of pathogens associated with the disease. Considering the difficulty in carrying out effective treatment with antimicrobials, it is necessary to propose alternatives that improve the clinical status of the patients. With this purpose, in a previous study, the safety and immunostimulant capacity of a polyvalent lysate designated UNAM-HIMFG prepared with different bacteria isolated during a prospective study of chronic urinary tract infection (CUTI) was evaluated. In this work, using an animal model, results are presented on the immunostimulant and protective activity of the polyvalent UNAM-HIMFG lysate to define its potential use in the control and treatment of CUTI. Female Balb/c mice were infected through the urethra with Escherichia coli CFT073 (UPEC O6:K2:H1) strain; urine samples were collected before the infection and every week for up to 60 days. Once the animals were colonized, sublingual doses of UNAM-HIMFG lysate were administrated. The colonization of the bladder and kidneys was evaluated by culture, and their alterations were assessed using histopathological analysis. On the other hand, the immunostimulant activity of the compound was analyzed by qPCR of spleen mRNA. Uninfected animals receiving UNAM-HIMFG lysate and infected animals administered with the physiological saline solution were used as controls. During this study, the clinical status and evolution of the animals were evaluated. At ninety-six hours after infection, the presence of CFT073 was identified in the urine of infected animals, and then, sublingual administration of UNAM-HIMFG lysate was started every week for 60 days. The urine culture of mice treated with UNAM-HIMFG lysate showed the presence of bacteria for three weeks post-treatment; in contrast, in the untreated animals, positive cultures were observed until the 60th day of this study. The histological analysis of bladder samples from untreated animals showed the presence of chronic inflammation and bacteria in the submucosa, while tissues from mice treated with UNAM-HIMFG lysate did not show alterations. The same analysis of kidney samples of the two groups (treated and untreated) did not present alterations. Immunostimulant activity assays of UNAM-HIMFG lysate showed overexpression of TNF-α and IL-10. Results suggest that the lysate activates the expression of cytokines that inhibit the growth of inoculated bacteria and control the inflammation responsible for tissue damage. In conclusion, UNAM-HIMFG lysate is effective for the treatment and control of CUTIs without the use of antimicrobials.

Asunto(s)

Infecciones por Escherichia coli , Ratones Endogámicos BALB C , Vejiga Urinaria , Infecciones Urinarias , Escherichia coli Uropatógena , Animales , Infecciones Urinarias/microbiología , Infecciones Urinarias/inmunología , Femenino , Ratones , Vejiga Urinaria/microbiología , Vejiga Urinaria/inmunología , Vejiga Urinaria/patología , Vejiga Urinaria/efectos de los fármacos , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/microbiología , Escherichia coli Uropatógena/inmunología , Escherichia coli Uropatógena/patogenicidad , Modelos Animales de Enfermedad , Adyuvantes Inmunológicos/farmacología , Lisados Bacterianos

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Urinary tract infections (UTIs) constitute one of the main complications in kidney recipients, increasing both morbidity and mortality. Due to the resurgence of antimicrobial resistance, new prophylactic approaches are being investigated. Nitrofurantoin is an antibiotic from the nitrofuran group that is effective against several Gram-negative and Gram-positive organisms; hence, there has been a resurgence in its prescription for treating MDR pathogens. Objectives: This study aims to assess the effectiveness of nitrofurantoin as an add-on to conventional therapy (amikacin + ceftriaxone or cefotaxime) for the treatment of urinary tract infections in kidney recipients. Methods: In a prospective cohort study, we included patients who received a kidney in a tertiary-care hospital. According to the intensive care specialist, group 1 patients were treated with the conventional prophylactic treatment plus nitrofurantoin as an add-on. Group 2 patients were treated only with the conventional prophylactic treatment. They were followed-up for 3 months, and the incidence of urinary tract infections was reported. Results: The UTI incidence for group 1 at 3 months was 20.6%, and for group 2, it was 20.0%; no statistical difference between treatments was observed (p = 0.9). The most commonly isolated pathogens were E. coli (28.5) and K. pneumonie (28.5%). The factor most associated with developing a UTI was female gender (aHR: 7.0; 95% IC 2.3-20.9, p < 0.001). Conclusions: In our cohort study, nitrofurantoin as an add-on in conventional therapy did not prove to be effective in preventing UTI development; therefore, other treatment options should be considered as a part of prophylactic treatment.

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Human Papillomavirus (HPV), a prevalent sexually transmitted infection, comprises high-risk (HR-HPV) and low-risk (LR-HPV) viruses, the former posing a high risk for developing malignancies whereas the latter mainly for benign warts. Despite increasing awareness of HPV's impact on men's health, the influence of HR-HPV and LR-HPV urogenital infections on male fertility potential remains uncertain. This study aimed to investigate whether male urogenital infection with HR- or LR-HPV associates with impaired sperm quality, oxidative stress, and inflammation. A total of 205 male patients attending an urology clinic were enrolled. Semen samples were analyzed for HPV using PCR and genotyped by RFLP. Semen quality was evaluated following WHO guidelines. Semen leukocytes, reactive oxygen species (ROS), and sperm viability were analyzed using flow cytometry. HPV was detected in 19% (39/205) of semen samples. HR-HPV infections were more prevalent, with HPV-16 being the most frequent genotype. Neither HR-HPV nor LR-HPV were associated with significant alterations in routine sperm quality parameters. However, HR-HPV+ individuals showed significantly higher levels of sperm necrosis and exhibited increased proportions of ROS+ spermatozoa compared to LR-HPV+ or control individuals. Furthermore, no significant semen inflammation was detected in patients infected with either HR-HPV or LR-HPV, and unexpectedly reduced semen leukocytes and inflammatory cytokines (IL-6 and IL-1ß) were observed in HR-HPV+ patients compared to controls. These observations underscore the importance of comprehensive HPV screening, including genotyping, in urology and fertility clinics to understand the progression of the infection, potential adverse effects on reproductive health, and the oncogenic risks involved.

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Papillomaviridae , Infecciones por Papillomavirus , Análisis de Semen , Semen , Espermatozoides , Humanos , Masculino , Infecciones por Papillomavirus/virología , Adulto , Espermatozoides/virología , Semen/virología , Papillomaviridae/genética , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismo , Genotipo , Adulto Joven , Inflamación , Estrés Oxidativo , Genitales Masculinos/virología , Adolescente , Citocinas/metabolismo

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Resumen El tracto oblicuo frontal (TOF) conecta el área mo tora suplementaria (AMS) con la pars opercularis. Su rol en el lenguaje y su implicancia en la cirugía de gliomas siguen en discusión. Presentamos un estu dio anatomoquirúrgico de tres casos con resolución quirúrgica. Se operaron tres pacientes con gliomas en el lóbu lo frontal izquierdo utilizando protocolo de paciente despierto con técnicas de mapeo cortical y subcortical realizando evaluación motora y del lenguaje. Las trac tografías fueron realizadas con el software DSI Studio. Los tres pacientes presentaron inhibición intraopera toria del lenguaje mediante la estimulación subcortical de TOF. La resección en contacto con el TOF se correla cionó con déficits del lenguaje en todos los casos y en dos casos déficits en la iniciación del movimiento. Todos los pacientes recuperaron su déficit a los seis meses postoperatorios. En conclusión, se ha logrado reconstruir al tracto. Éste presenta una complejidad anatómica y funcional, que apoya la idea de su mapeo y preservación en la cirugía de gliomas. Futuros estudios interdisciplinarios son necesarios para determinar el carácter transitorio o permanente de los déficits.

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Abstract The frontal aslant tract (FAT) connects the supple mentary motor area (SMA) with the pars opercularis. Its role in language and its implications in glioma sur gery remain under discussion. We present an anatomo-surgical study of three cases with surgical resolution. Three patients with gliomas in the left frontal lobe were operated on using an awake patient protocol with cortical and subcortical mapping techniques, conduct ing motor and language evaluations. Tractography was performed using DSI Studio software. All three patients showed intraoperative language inhibition through subcortical stimulation of the FAT. Resection involving the FAT correlated with language deficits in all cases and movement initiation deficits in two cases. All patients recovered from their deficits at six months postoperatively. In conclusion, the tract has been successfully re constructed, showing both anatomical and functional complexity, supporting the idea of its mapping and preservation in glioma surgery. Future interdisciplin ary studies are necessary to determine the transient or permanent nature of the deficits.

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Resumo O cateter vesical de longa permanência pode ser indicado em situações clínicas, como nas doenças crônicas do sistema genitourinário ou neurológico. Além dos riscos de infecção, traumas e sangramentos, a permanência do cateter pode afetar dimensões psicoemocionais e socioeconômicas. Objetivamos compreender como a necessidade de uso do cateter urinário por um longo prazo afeta a autopercepção, as interrelações e o autocuidado deste paciente. Realizamos um estudo qualitativo, descritivo, a partir da entrevista de 17 pacientes, e aplicamos a análise temática e o pensamento complexo. Os diferentes prognósticos e as expectativas em relação ao cateter influenciaram a autopercepção, a adaptação, sua aceitação ou negação. A presença do cateter, seja como medida curativa ou para conforto, pode afetar a autoimagem e a sexualidade, gerar inseguranças e incertezas, que requerem compreensão da multidimensionalidade das situações, que sofrem interferências do meio pessoal, familiar e social, bem como da capacidade dos sistemas de saúde para o seu enfrentamento. Apesar dos desafios, a maioria dos participantes relatou disposição favorável para o autocuidado, seja para viabilizar retirada do cateter, ou para prevenir agravos em indicações vitalícias.

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Abstract A long-term indwelling catheter may be indicated in clinical situations, such as chronic diseases of the genitourinary or neurological systems. In addition to the risks of infection, trauma, and bleeding, a catheter's permanence can affect psycho-emotional and socioeconomic dimensions. We aimed to understand how the need to use a long-term indwelling catheter affects this patient's self-perception, interrelationships, and self-care. We carried out a qualitative, descriptive study based on interviews with 17 patients, and applied thematic analysis and complex thinking. The different prognoses and expectations regarding the catheter influenced self-perception, adaptation, acceptance, or denial. The presence of a catheter, whether as a curative measure or for comfort, can affect self-image and sexuality, and generate insecurities and uncertainties, which require understanding the multidimensionality of situations that suffer interference from the personal, family, and social environment, as well as health systems' capacity to deal with it. Despite the challenges, the majority of participants reported a favorable disposition towards self-care, whether to enable catheter removal or to prevent injuries in lifelong indications.

RESUMEN

AIMS: It is well established that intracellular cAMP contributes to the relaxation of vas deferens smooth muscle. In many tissues, intracellular cAMP is actively transported to the extracellular space, where it exerts regulatory functions, via its metabolite adenosine. These actions take place through the cAMP conversion to adenosine by ectoenzymes, a process called "extracellular cAMP-adenosine pathway". Herein, we investigated whether, in addition to ATP, extracellular cAMP might be an alternative source of adenosine, influencing the contraction of vas deferens smooth muscle. MAIN METHODS: The effects of cAMP, 8-Br-cAMP and adenosine were analyzed in the isometric contractions of rat vas deferens. cAMP efflux was analyzed by measuring extracellular cAMP levels after exposure of vas deferens segments to isoproterenol and forskolin in the presence or absence of MK-571, an inhibitor of MRP/ABCC transporters. KEY FINDINGS: While 8-Br-cAMP, a cell-permeable cAMP analog, induced relaxation of KCl-precontracted vas deferens, the non-permeant cAMP increased the KCl-induced contractile response, which was mimicked by adenosine, but prevented by inhibitors of ecto-5'-nucleotidase or A1 receptors. Our results also showed that isoproterenol and forskolin increases cAMP efflux via an MRP/ABCC transporter-dependent mechanism, since it is inhibited by MK-571. SIGNIFICANCE: Our data show that activation of ß-adrenoceptors and adenylyl cyclase increases cAMP efflux from vas deferens tissue, which modulates the vas deferens contractile response via activation of adenosine A1 receptors. Assuming that inhibition of vas deferens contractility has been proposed as a strategy for male contraception, the extracellular cAMP-adenosine pathway emerges as a potential pharmacological target that should be considered in studies of male fertility.

Asunto(s)

5'-Nucleotidasa , AMP Cíclico , Contracción Muscular , Ratas Wistar , Receptor de Adenosina A1 , Conducto Deferente , Masculino , Animales , Conducto Deferente/efectos de los fármacos , Conducto Deferente/metabolismo , AMP Cíclico/metabolismo , 5'-Nucleotidasa/metabolismo , Receptor de Adenosina A1/metabolismo , Receptor de Adenosina A1/efectos de los fármacos , Ratas , Contracción Muscular/efectos de los fármacos , Adenosina/farmacología , Adenosina/análogos & derivados , Adenosina/metabolismo , Isoproterenol/farmacología , Músculo Liso/efectos de los fármacos , Músculo Liso/metabolismo , Colforsina/farmacología

RESUMEN

Mycoplasma (M.) hyopneumoniae is a primary etiological agent of porcine enzootic pneumonia (PEP), a disease that causes significant economic losses to pig farming worldwide. Current commercial M. hyopneumoniae vaccines induce partial protection, decline in preventing transmission of this pathogen or inducing complete immunity, evidencing the need for improving vaccines against PEP. In our study, we aimed to test the effectiveness of the SBA-15 ordered mesoporous silica nanostructured particles as an immune adjuvant of a vaccine composed of M. hyopneumoniae strain 232 proteins encapsulated in SBA-15 and administered by intramuscular route in piglets to evaluate the immune responses and immune-protection against challenge. Forty-eight 24-day-old M. hyopneumoniae-free piglets were divided into four experimental groups with different protocols, encompassing a commercial vaccine against M. hyopneumoniae, SBA-15 vaccine, SBA-15 adjuvant without antigens and a non-immunized group. All piglets were challenged with the virulent strain 232 of M. hyopneumoniae. Piglets that received the SBA-15 and commercial vaccine presented marked immune responses characterized by anti-M. hyopneumoniae IgA and IgG antibodies in serum, anti-M. hyopneumoniae IgA antibodies in nasal mucosa and showed an upregulation of IL-17 and IL-4 cytokines and downregulation of IFN-γ in lungs 35 days post-infection. Piglets immunized with SBA-15 vaccine presented a reduction of bacterial shedding compared to piglets immunized with a commercial bacterin. In addition, piglets from SBA-15 adjuvant suspension group presented increased IL-17 gene expression in the lungs without involvement of Th1 and Th2 responses after challenge. These results indicated that SBA-15 vaccine induced both humoral and cell-mediated responses in the upper respiratory tract and lungs, first site of replication and provided protection against M. hyopneumoniae infection with a homologous strain with reduction of lung lesions and bacterial shedding. Finally, these results enhance the potential use of new technologies such as nanostructured particles applied in vaccines for the pig farming industry.

Asunto(s)

Adyuvantes Inmunológicos , Anticuerpos Antibacterianos , Vacunas Bacterianas , Mycoplasma hyopneumoniae , Nanoestructuras , Neumonía Porcina por Mycoplasma , Dióxido de Silicio , Vacunas de Productos Inactivados , Animales , Mycoplasma hyopneumoniae/inmunología , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/inmunología , Neumonía Porcina por Mycoplasma/prevención & control , Neumonía Porcina por Mycoplasma/inmunología , Porcinos , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Anticuerpos Antibacterianos/sangre , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Derrame de Bacterias , Citocinas/inmunología , Pulmón/inmunología , Pulmón/microbiología , Inyecciones Intramusculares

RESUMEN

Bioactive peptides derived from native proteins modulate physiological processes in the metabolic pathways. Given that multiple protocols in the literature mimic the digestion of dietary components, gathering studies that use such models directed at protein digestion processes is critical. This systematic review aimed to gather evidence that adopted adequate experimental models to simulate human protein digestion. The databases searched were PubMed, Web of Science, ScienceDirect, Embase, Virtual Health Library, and Scopus. A total of 1985 articles were found, resulting in 20 eligible in vitro studies. The Office of Health Assessment and Translation was used to evaluate methodological quality. Seven studies used plant-based protein sources, twelve used animal protein sources, and one used both. The duration of the oral phase varied, although 60% of the studies employed a protein digestion period of 120 min. Amylase, pepsin, and pancreatin enzymes were utilized in 40% of the studies, with pH levels of 7, 3, and 7, respectively, during the oral, gastric, and intestinal phases. The INFOGEST harmonized static model was adopted by 65% of the studies; INFOGEST is the most effective model for simulating gastrointestinal protein processes in humans and can be used to answer several research questions because it describes experimental conditions close to the human physiological situation.

Asunto(s)

Digestión , Tracto Gastrointestinal , Digestión/fisiología , Humanos , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/fisiología , Modelos Biológicos , Proteínas en la Dieta/metabolismo , Animales

RESUMEN

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare subset of urothelial cancers with poor prognosis. No consensus exists on the benefit of adjuvant immunotherapy for patients with UTUCs after nephroureterectomy with curative intent and the existing studies are limited. Herein, this study aimed to evaluate the effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk UTUC. METHODS: A retrospective study was conducted on 63 patients with high-risk UTUC who received tislelizumab with or without gemcitabine-cisplatin (GC) chemotherapy regimen after surgery between January 2020 and December 2022. Data on demographic and clinical characteristics, surgical, outcomes, prognostic factors, and safety were collected and analyzed. RESULTS: Among the 63 patients with high-risk UTUC, the median age was 66 years (interquartile range 57-72), with 33 (52%) being male. The majority of patients with staged pT3 (44%) and pN0 (78%) disease. Fifty-one patients (81%) received tislelizumab plus GC chemotherapy, and 12 (19%) were treated with tislelizumab monotherapy. After the median follow-up of 26 months (range 1-47), 49 (78%) patients achieved stable disease. The 2-year disease-free survival (DFS) and 2-year overall survival were 78.68% (95% CI: 60.02-87.07%) and 81.40% (95% CI: 68.76-89.31%), respectively. The cycles of GC chemotherapy were independent prognostic factors for survival, with higher DFS (hazard ratio = 0.68, 95% CI, 0.50-0.93; p = 0.016) observed in the subgroup undergoing ≥ 3 cycles versus < 3 cycles of GC chemotherapy. Fifty-eight patients (92%) experienced at least one treatment-related adverse event (TRAE), with grade 3-4 TRAEs occurring in 13%. The most common grade 3-4 TRAEs were decreased white blood cells, thrombocytopenia, and ulcers. CONCLUSIONS: The study demonstrates promising clinical benefits and a manageable safety profile of the tislelizumab-based adjuvant regimen for patients with high-risk UTUC. This suggests that adjuvant immunotherapy represents a potential therapeutic strategy for this population.

RESUMEN

OBJECTIVE: Translating and cross-culturally adapting the CFAbd-Score, Cystic Fibrosis (CF) Abdominal Score, to use in Brazilian spoken Portuguese. The CFAbd-Score is a questionnaire for assessing CF-related abdominal symptoms and their influence on the quality of life (QoL). It comprises 28 questions on five domains: abdominal pain, bowel movements, eating and appetite, gastroesophageal reflux symptoms, and the impact of gastrointestinal (GI) symptoms on QoL. METHOD: Cross-cultural adaptation included assessment of conceptual and item equivalence, semantic, operational, and measurement equivalence. Content validity was assessed. The validation and psychometric analysis phase included 97 people with CF (pwCF), median age:14.58y (IQR 9/19), and 105 healthy individuals, 15.10y (IQR 9/20). Exploratory factor analysis (FA) identified retained factors. Internal consistency of the extracted domains was evaluated using Cronbach's α, and the Kaiser-Meyer-Olkin test (KMO) was used to check the sample adequacy. Bartlett's test tested the null hypothesis that the correlation matrix is an identity matrix. RESULTS: All items were considered relevant to the construct and good semantic equivalence of the version was recognized. FA showed the appropriate weight of all items and good internal consistency, with Cronbach's alpha 0.89. Bartlett's test significance level (p < 0.001) and KMO coefficient of 0.72 indicated good adequacy for structure. Internal consistency coefficients (Cronbach's alpha) were good for abdominal pain: 0.84; abdominal bloating: 0.73; flatulence: 0.76; heartburn: 0.81, and low for reflux: 0.54. CONCLUSION: The CFAbd-Score was adapted to the Brazilian spoken Portuguese and demonstrated content and semantic equivalence. The final version showed appropriate validity, and internal consistency, preserving the psychometric properties of the original version.

RESUMEN

The objective of this study was to determine the prevalence of Streptococcus equi (S. equi subsp equi and S. equi subsp zooepidemicus) in the state of Santa Catarina and evaluate the antimicrobial susceptibility of the isolates. For this, 420 nasal swab samples were collected from randomly selected horses. Isolation and phenotypic characterization of the bacteria were performed by sowing on 5% sheep blood agar, followed by analysis of morphotinctorial characteristics and biochemical analysis. To differentiate the main beta-hemolytic Streptococcus in horses, the fermentation profiles of the sugar's lactose, maltose, sorbitol, and trehalose were used, which were confirmed at the subspecies level by the PCR technique. The antimicrobial susceptibility panel was defined by the disk diffusion method, testing 13 antimicrobials from ten different classes, all regularly used in equine medical clinics, followed by the calculation of the multiple antimicrobial resistance index. Ten strains of S. equi were isolated, with a prevalence of 2.38% (10/420). Of the total positive samples, 3% (3/10) were confirmed as belonging to S. equi subsp equi and 70% (7/10) were confirmed as belonging to S. zooepidemicus. Multidrug resistance was observed in 60% (6/10) of isolates. The antimicrobial with the greatest resistance was clindamycin with 70% (7/10), followed by beta-lactams, with 40% (4/10) resistance to penicillin and 30% (3/10) to ceftiofur. The isolates were 100% (10/10) sensitive to gentamicin, chloramphenicol, levofloxacin, and vancomycin. This was the first study carried out in the state, and based on these data, it can be said that Santa Catarina has a low prevalence of S. equi and the presence of multi-resistant strains of S. equi was confirmed in the equine herd in Santa Catarina.