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1.
World J Urol ; 42(1): 314, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730089

RESUMO

PURPOSE: To provide a descriptive report of mortality and morbidity in the first 30 days of diagnosis of urosepsis. Secondary aim is to identify risk factors of unfavourable outcomes. METHODS: Prospective observational multicentre cohort study conducted from September 2014 to November 2018 in European hospitals. Adult patients (≥ 18 years) diagnosed with acute urosepsis according to Sepsis-2 criteria with confirmed microbiological infection were included. Outcomes were classified in one of four health states: death, multiple organ failure, single organ failure, and recovery at day 30 from onset of urosepsis. Descriptive statistics and ordinal logistic regression analysis was performed. RESULTS: Three hundred and fifty four patients were recruited, and 30-day mortality rate was 2.8%, rising to 4.6% for severe sepsis. All patients who died had a SOFA score of ≥ 2 at diagnosis. Upon initial diagnosis, 79% (n = 281) of patients presented with OF. Within 30 days, an additional 5% developed OF, resulting in a total of 84% affected. Charlson score (OR 1.14 CI 1.01-1.28), patients with respiratory failure at baseline (OR 2.35, CI 1.32-4.21), ICU admission within the past 12 months (OR 2.05, CI 1.00-4.19), obstruction causative of urosepsis (OR 1.76, CI 1.02-3.05), urosepsis with multi-drug-resistant(MDR) pathogens (OR 2.01, CI 1.15-3.53), and SOFA baseline score ≥ 2 (OR 2.74, CI 1.49-5.07) are significantly associated with day 30 outcomes (OF and death). CONCLUSIONS: Impact of comorbidities and MDR pathogens on outcomes highlights the existence of a distinct group of patients who are prone to mortality and morbidity. These findings underscore the need for the development of pragmatic classifications to better assess the severity of UTIs and guide management strategies. STUDY REGISTRATION: Clinicaltrials.gov registration number NCT02380170.


Assuntos
Sepse , Infecções Urinárias , Humanos , Estudos Prospectivos , Feminino , Masculino , Fatores de Risco , Idoso , Infecções Urinárias/epidemiologia , Sepse/mortalidade , Sepse/epidemiologia , Pessoa de Meia-Idade , Fatores de Tempo , Idoso de 80 Anos ou mais , Estudos de Coortes
2.
Eur Urol ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38744631

RESUMO

The European Association of Urology Urological Infections Guidelines Panel is proposing a new classification scheme for categorizing urinary tract infections (UTIs) into uncomplicated and complicated types. This classification would provide clarity and facilitate effective clinical management of UTIs, and acknowledges the importance of addressing clinical and sex-specific nuances in the care of individual patients.

3.
Ann Transl Med ; 12(2): 32, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38721449

RESUMO

Descending perineal syndrome (DPS) was described by Parks et al. as descent of the anus on straining, typically 3-4 cm below a line drawn from the coccyx to the lower end of the. DPS is associated with obstructed defecation, with increased bulging of the perineum with straining, although perineal descent can also be seen at rest. In their review, Chaudhry and Tarnay stated: "It is controversial whether surgical management is even an option for patients with DPS". The deep transversus perinei (DTP) ligaments are the suspensory ligaments of the perineal body (PB). DTP are approximately 4 cm long. They attach behind the upper 2/3 and lower 1/3 of the descending ramus. If, at childbirth, the PB is overstretched and displaced laterally and inferiorly, the DTP lengthens. DPS is described as descent of the anus on straining, typically 3-4 cm below a line drawn from the coccyx to the lower end of the symphysis. DPS is associated with obstructed and often, assisted defecation, with increased bulging of the perineum with straining descent of the anus on straining. The surgical methodology begins as a standard PB repair which dissects the rectum from the vagina and PB and approximates the displaced components of the PB. We added an additional step: identifying the DTPs, shortening and reinforcing them with the Tissue Fixation System (TFS) minisling or No. 2 polyester sutures. High cure rates for obstructed defecation were achieved with the TFS minisling, and initial results using No. 2 polyester sutures are favourable. The key messages from both operations is DPS is caused by stretching and elongation of DPS ligaments, and these are surgically repairable.

4.
Ann Transl Med ; 12(2): 26, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38721452

RESUMO

The remit of this review is confined to the experimental scientific works and surgeries based on the Integral Theory Paradigm (ITP). Chronic pelvic pain (CPP) is a major societal problem which is said to occur in up to 20% of women. The pathogenesis of CPP of "unknown origin" is said to be unknown and CPP is said to be incurable. According to the ITP, however, CPP is said to be mainly caused by the inability of loose or weak uterosacral ligaments (USLs) to mechanically support visceral nerve plexuses (VPs), T11-L2 and S2-4. These fire off de novo impulses, interpreted by the cortex as pain coming from the end organs. CPP, when it occurs simultaneously in multiple pelvic sites, is associated with uterine/apical prolapse (often minimal) and bladder symptoms such as overactive bladder (OAB), nocturia, retention. This combination of symptoms was described in 1993 as the "posterior fornix syndrome" (PFS). As such, CPP when associated with the PFS, is potentially curable by surgical repair of USLs. However, patients with CPP generally complain only of one symptom, CPP. This is known as the "Pescatori iceberg" effect. Other PFS symptoms are "under the surface" and must be sought out by direct questioning. The diagnostic algorithm is helpful in locating other associated symptoms. Definitive diagnosis of CPP, caused by USL laxity, is immediate alleviation of pain by mechanical support of USLs by using the speculum test or by tampons in the posterior fornix. Treatment of CPP can be non-surgical, by strengthening USLs by squatting exercises, supporting USLs mechanically with tampons or USL surgery. Coexisting bladder symptoms are (variously) improved or cured. URL for CPP https://www.pelviperineology.org/volume/36/issue/3.

5.
Eur Urol ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38714379

RESUMO

BACKGROUND AND OBJECTIVE: Urological infections significantly impact the wellbeing and quality of life of individuals owing to their widespread occurrence and diverse clinical manifestations. The objective of the guidelines panel was to provide evidence-based guidance on the diagnosis, treatment, and prevention of urinary tract infections (UTIs) and male accessory-gland infections, while addressing crucial public health aspects related to infection control and antimicrobial stewardship. METHODS: For the 2024 guidelines on urological infections, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasise the importance of a thorough medical history and physical examination for patients with urological infections. The guidelines stress the role of antimicrobial stewardship to combat the rising threat of antimicrobial resistance, providing recommendations for antibiotic selection, dosing, and duration on the basis of the latest evidence. CONCLUSIONS AND CLINICAL IMPLICATIONS: This overview of the 2024 EAU guidelines offers valuable insights into managing urological infections and are designed for effective integration into clinical practice. PATIENT SUMMARY: The European Association of Urology has issued an updated guideline on urological infections. The guidelines provide recommendations for diagnosis, treatment, and prevention, with a particular focus on minimising antibiotic use because of the increasing global threat of antimicrobial resistance.

6.
Urologie ; 2024 Apr 23.
Artigo em Alemão | MEDLINE | ID: mdl-38653788

RESUMO

Priapism is defined as penile erection lasting more than four hours that is unrelated to sexual arousal. Priapism is classified based on the oxygenation of the penile tissue into ischemic and non-ischemic subtypes. As the most common form, ischemic priapism is usually associated with pain and carries a significant risk of permanent loss of erectile function; thus, rapid intervention is necessary. Initial therapy consists of corporal aspiration and injection of sympathomimetic agents. If detumescence is not achieved, a cavernosal shunt is necessary. Non-ischemic priapism is less common than the ischemic type and is usually the result of perineal trauma. In this subtype, there is usually no pain and treatment is initially conservative. Recurrent (stuttering) priapism is a variant of the ischemic subtype, but is self-limiting and usually occurs during sleep with a duration of less than three to four hours. In the case of prolonged erection, therapy is analogous to that of the ischemic subtype.

7.
Dtsch Arztebl Int ; (Forthcoming)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38686602

RESUMO

BACKGROUND: Urinary tract infection has a one-year prevalence of 11% in women and ranges among the most common reasons for consulting a primary care physician and for receiving a prescription for antibiotics. In the case of recurrent urinary tract infection (rUTI), there are questions about the further work-up, treatment, and preventive measures. METHODS: The systematic literature search performed for the update of the German clinical practice guideline on uncomplicated urinary tract infection (043-044) (up to February 2022) was supplemented with a selective search for clinical trials (up to August 2023). RESULTS: Urine culture and ultrasonography are reasonable steps in the diagnostic evaluation of rUTI. Further invasive testing is suggested for men but is not routinely indicated for women. Antibiotics are among the most effective preventive measures (risk ratio [RR] 0.15, 95% confidence interval [0.1; 0.3]) but carry a high risk of side effects. Non-antibiotic preparations such as cranberry juice (RR 0.74 [0.5; 0.99]), mannose (RR 0.23 [0.14; 0.37]), and vaginal estrogen (RR, 0.42 [0.30; 0.59]) can also reduce the infection rate, with a low risk of side effects. Increased daily fluid intake has been shown to lower infection rates in the short term (odds ratio [OR] 0.13 [0.07; 0.25]); the use of hygienically advisable wiping techniques after passing stool or urine has been little studied but can be implemented with no risk. CONCLUSION: rUTI poses a challenge for the treating physician. The measures to be taken must be considered on an individual basis. Vulnerable groups, such as older patients, need special attention.

8.
Infect Dis Clin North Am ; 38(2): 229-240, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38575493

RESUMO

Urinary tract infection (UTI) is a very common disease that is accompanied by various complications in the affected person. UTI triggers diverse inflammatory reactions locally in the infected urinary bladder and kidney, causing tissue destruction and organ failure. Moreover, systemic responses in the entire body carry the risk of urosepsis with far-reaching consequences. Understanding the cell-, organ-, and systemic mechanisms in UTI are crucial for prevention, early intervention, and current therapeutic approaches. This review summarizes the scientific advances over the last 10 years concerning pathogenesis, prevention, rapid diagnosis, and new treatment approaches. We also highlight the impact of the immune system and potential new therapies to reduce progressive and recurrent UTI.


Assuntos
Infecções Urinárias , Humanos , Infecções Urinárias/diagnóstico , Infecções Urinárias/prevenção & controle , Antibacterianos/uso terapêutico
9.
Br J Pharmacol ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676555

RESUMO

BACKGROUND AND PURPOSE: With increasing life expectancy, benign prostatic hyperplasia (BPH) consequently affects more ageing men, illustrating the urgent need for advancements in BPH therapy. One emerging possibility may be the use of oxytocin antagonists to relax smooth muscle cells in the prostate, similar to the currently used (although often associated with side effects) α1-adrenoceptor blockers. EXPERIMENTAL APPROACH: For the first time we used live-imaging, combined with a novel image analysis method, to investigate the multidirectional contractions of the human prostate and determine their changes in response to oxytocin and the oxytocin antagonists atosiban and cligosiban. Human prostate samples were obtained and compared from patients undergoing prostatectomy due to prostate cancer as well as from patients with transurethral resection of prostate tissue due to severe BPH. KEY RESULTS: The two cohorts of tissue samples showed spontaneous multidirectional contractions, which significantly increased after the addition of oxytocin. Different to atosiban, which showed ambiguous effects of short duration, only long-acting cligosiban reliably prevented, as well as counteracted, any contractile oxytocin effect. Furthermore, cligosiban visibly reduced not only oxytocin-induced contractions, but also showed intrinsic activity to relax prostatic tissue. CONCLUSION AND IMPLICATIONS: Thus, the oxytocin antagonist cligosiban could be an interesting candidate in the search for novel BPH treatment options.

10.
Br J Cancer ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649788

RESUMO

BACKGROUND: Immune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells are found in other cancer entities, but their contributions to TGCT are unknown. METHODS: Human testis specimens from independent patient cohorts were analyzed using immunohistochemistry, flow cytometry and single-cell RNA sequencing (scRNA-seq) with special emphasis on delineating T cell subtypes. RESULTS: Profound changes in immune cell composition within TGCT, shifting from macrophages in normal testes to T cells plus B and dendritic cells in TGCT, were documented. In most samples (96%), the CD4+ T cell frequency exceeded that of CD8+ cells, with decreasing numbers from central to peripheral tumor areas, and to tumor-free, contralateral testes. T cells including Treg and Tfh were most abundant in seminoma compared to mixed tumors and embryonal carcinoma. CONCLUSION: Despite considerable heterogeneity between patients, T cell subtypes form a key part of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, to assess patients' prognosis, and as putative targets for personalized immunotherapy.

11.
Urologie ; 2024 Apr 19.
Artigo em Alemão | MEDLINE | ID: mdl-38639782

RESUMO

Urinary tract infections vary widely in their clinical spectrum, ranging from uncomplicated cystitis to septic shock. Urosepsis accounts for 9-31% of all cases of septicemia and is often associated with nosocomial infections. A major risk factor for urosepsis is the presence of obstructive uropathy, caused by conditions such as urolithiasis, tumors, or strictures. The severity and course of urosepsis depend on both the virulence of the pathogen and the patient's specific immune response. Prompt therapy, including antimicrobial treatment and eradication of the infection source, along with supportive measures for circulatory and respiratory stabilization, and adjunctive therapies such as hemodialysis and glucocorticoid therapy, is crucial. Due to demographic changes, an increase in cases of urosepsis is expected-thus, it is of utmost importance for urologists to be familiar with targeted diagnostics and effective treatment.

12.
J Robot Surg ; 18(1): 174, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613654

RESUMO

Prostate cancer patients often have other health conditions and take anticoagulants. It was believed that surgery under anticoagulants could worsen surgical results. This study aims to explore the safety of robot-assisted prostatectomy in anticoagulated patients, without any exclusion criteria. The study included 500 patients who underwent RARP by a single surgeon between April 2019 and August 2022. Patients were divided into two groups: Group 1, consisting of 376 men (75.2%), did not receive any anticoagulation, while Group 2, with 124 patients (24.8%), received different forms of anticoagulation. Then, the anticoagulation group was divided into 4 subgroups according to their definite anticoagulation: the aspirin 15.6%, new oral anticoagulants (NOAC) 5.4%, Vitamin K antagonist (VKA) 2%, and dual-antiplatelet therapy (DAPT) 1.8% subgroup. Postoperative complications and readmission rates were compared between the two study groups and subgroups. Patients in the combined group 2 were older and they also carried more comorbidities compared to men in group 1 (p = 0.03, p = 0.001).The study groups had similar oncological results, with 40.4% of patients having locally advanced cancers. Catheter days were longer in the anticoagulation group (4.5 vs 4 days, p = 0.001). No significant differences were observed between study groups for overall, minor, and major complications (p = 0.160, 0.100, and 0.915, respectively). In addition, readmissions were low (5.6%) and similar between the study groups (p = 0.635). Under cautious management, RARP under diverse anticoagulation regimes is safe and has comparable results to men with no medications. Further prospective studies must be conducted to confirm our findings.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgiões , Masculino , Humanos , Anticoagulantes/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Prostatectomia
13.
Artigo em Inglês | MEDLINE | ID: mdl-38555411

RESUMO

BACKGROUND: Even if Meares-Stamey 4-glass (M&S) test is regarded a decisive tool for diagnosing prostatitis its use is only rarely performed in everyday clinical practice. Here, we analyze if the diagnostic yield of the M&S test could be improved by a pre-test categorization of patients due to undergo a M&S test. METHODS: All clinical and microbiological data of patients who underwent M&S test in two urological centers from January 2004 to December 2021 were analyzed in this retrospective cohort study. One center has a dedicated staff member for the study of prostatitis (Cohort I), while the other center is a general urological unit (Cohort II). All patients were divided into 3 groups on the basis of the assembled data: patients with symptoms related to prostatitis only (Group I), patients with symptoms related to both prostatitis and BPH (Group II), patients with symptoms related to BPH only (Group III). The rates of positive microbiological results in each group were compared. RESULTS: In the whole period, 9347 patients were analyzed and categorized as follows: Group I, 1884; Group II, 5151; Group III, 2312. Three-thousand and eight-hundred twenty-three patients showed positive culture results (40.9%). The most common isolated species was Escherichia coli (49.7%), followed by Enteroccus spp. (31.8%). The rates of positive M&S tests in the different symptom groups were: Group I, 1532 (81.4%); Group II, 1494 (29.0%); Group III, 797 (34.4%). The overall rate of positive M&S tests in each urology center showed that the center with a staff member who is dedicated to prostatitis studies (Cohort I) had a significantly higher rate of positive M&S tests than the general urological department (Cohort II) (64.3% vs 31.4%; p < 0.001). CONCLUSIONS: Symptom-based patient selection and dedicated staff members will increase the diagnostic yield of the M&S test and reduce the number of unnecessary tests.

14.
Lancet Infect Dis ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38458204

RESUMO

The absence of a consensus-based reference standard for urinary tract infection (UTI) research adversely affects the internal and external validity of diagnostic and therapeutic studies. This omission hinders the accumulation of evidence for a disease that imposes a substantial burden on patients and society, particularly in an era of increasing antimicrobial resistance. We did a three-round Delphi study involving an international, multidisciplinary panel of UTI experts (n=46) and achieved a high degree of consensus (94%) on the final reference standard. New-onset dysuria, urinary frequency, and urinary urgency were considered major symptoms, and non-specific symptoms in older patients were not deemed indicative of UTI. The reference standard distinguishes between UTI with and without systemic involvement, abandoning the term complicated UTI. Moreover, different levels of pyuria were incorporated in the reference standard, encouraging quantification of pyuria in studies done in all health-care settings. The traditional bacteriuria threshold (105 colony-forming units per mL) was lowered to 104 colony-forming units per mL. This new reference standard can be used for UTI research across many patient populations and has the potential to increase homogeneity between studies.

15.
N Engl J Med ; 390(7): 611-622, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38354140

RESUMO

BACKGROUND: Carbapenem-resistant Enterobacterales species and multidrug-resistant Pseudomonas aeruginosa are global health threats. Cefepime-taniborbactam is an investigational ß-lactam and ß-lactamase inhibitor combination with activity against Enterobacterales species and P. aeruginosa expressing serine and metallo-ß-lactamases. METHODS: In this phase 3, double-blind, randomized trial, we assigned hospitalized adults with complicated urinary tract infection (UTI), including acute pyelonephritis, in a 2:1 ratio to receive intravenous cefepime-taniborbactam (2.5 g) or meropenem (1 g) every 8 hours for 7 days; this duration could be extended up to 14 days in case of bacteremia. The primary outcome was both microbiologic and clinical success (composite success) on trial days 19 to 23 in the microbiologic intention-to-treat (microITT) population (patients who had a qualifying gram-negative pathogen against which both study drugs were active). A prespecified superiority analysis of the primary outcome was performed after confirmation of noninferiority. RESULTS: Of the 661 patients who underwent randomization, 436 (66.0%) were included in the microITT population. The mean age of the patients was 56.2 years, and 38.1% were 65 years of age or older. In the microITT population, 57.8% of the patients had complicated UTI, 42.2% had acute pyelonephritis, and 13.1% had bacteremia. Composite success occurred in 207 of 293 patients (70.6%) in the cefepime-taniborbactam group and in 83 of 143 patients (58.0%) in the meropenem group. Cefepime-taniborbactam was superior to meropenem regarding the primary outcome (treatment difference, 12.6 percentage points; 95% confidence interval, 3.1 to 22.2; P = 0.009). Differences in treatment response were sustained at late follow-up (trial days 28 to 35), when cefepime-taniborbactam had higher composite success and clinical success. Adverse events occurred in 35.5% and 29.0% of patients in the cefepime-taniborbactam group and the meropenem group, respectively, with headache, diarrhea, constipation, hypertension, and nausea the most frequently reported; the frequency of serious adverse events was similar in the two groups. CONCLUSIONS: Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem. (Funded by Venatorx Pharmaceuticals and others; CERTAIN-1 ClinicalTrials.gov number, NCT03840148.).


Assuntos
Antibacterianos , Ácidos Borínicos , Ácidos Carboxílicos , Cefepima , Meropeném , Infecções Urinárias , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Administração Intravenosa , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , beta-Lactamases/administração & dosagem , beta-Lactamases/efeitos adversos , beta-Lactamases/uso terapêutico , Ácidos Borínicos/administração & dosagem , Ácidos Borínicos/efeitos adversos , Ácidos Borínicos/uso terapêutico , Ácidos Carboxílicos/administração & dosagem , Ácidos Carboxílicos/efeitos adversos , Ácidos Carboxílicos/uso terapêutico , Cefepima/administração & dosagem , Cefepima/efeitos adversos , Cefepima/uso terapêutico , Quimioterapia Combinada , Hospitalização , Meropeném/administração & dosagem , Meropeném/efeitos adversos , Meropeném/uso terapêutico , Testes de Sensibilidade Microbiana , Pielonefrite/tratamento farmacológico , Pielonefrite/microbiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Farmacorresistência Bacteriana
16.
Lancet ; 403(10428): 741-755, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38342126

RESUMO

BACKGROUND: Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and a unique binding site, providing well balanced inhibition of two type II topoisomerase enzymes. Oral gepotidacin is under investigation to treat uncomplicated urinary tract infections. We aimed to compare the efficacy and safety of oral gepotidacin with that of nitrofurantoin in adolescent and adult female individuals with uncomplicated urinary tract infections. METHODS: EAGLE-2 and EAGLE-3 were phase 3, randomised, multicentre, double-blind, double-dummy, non-inferiority (10% margin) trials, in which patients were enrolled at 219 centres worldwide. Patients assigned female at birth, non-pregnant, aged 12 years or older, weighing 40 kg or more, with two or more symptoms of dysuria, frequency, urgency, or lower abdominal pain, and with evidence of urinary nitrite, pyuria, or both were eligible for inclusion. Patients were randomly assigned (1:1) centrally by interactive response technology to receive oral gepotidacin (1500 mg twice daily for 5 days) or oral nitrofurantoin (100 mg twice daily for 5 days), with randomisation stratified by age category and history of recurrent uncomplicated urinary tract infections. Patients, investigators, and the sponsor study team were masked to treatment assignment. The primary endpoint, therapeutic response (success or failure) at test-of-cure (ie, day 10-13), was evaluated in randomly assigned patients with nitrofurantoin-susceptible qualifying uropathogens (≥105 colony-forming units [CFU] per mL) and who received at least one dose of study treatment. Conforming to regulatory guidance, therapeutic success was defined as combined clinical success (ie, complete symptom resolution) and microbiological success (ie, reduction of qualifying uropathogens to <103 CFU/mL) without other systemic antimicrobial use. Safety analyses included patients who were randomly assigned and who received at least one dose of study treatment. The trials are registered with ClinicalTrials.gov, NCT04020341 (EAGLE-2) and NCT04187144 (EAGLE-3), and are completed. FINDINGS: Studies were undertaken from Oct 17, 2019, to Nov 30, 2022 (EAGLE-2), and from April 23, 2020, to Dec 1, 2022 (EAGLE-3). 1680 patients in EAGLE-2 and 1731 patients in EAGLE-3 were screened for eligibility, of whom 1531 and 1605 were randomly assigned, respectively (767 in the gepotidacin group and 764 in the nitrofurantoin group in EAGLE-2, and 805 in the gepotidacin group and 800 in the nitrofurantoin group in EAGLE-3). After an interim analysis, which was prospectively agreed as a protocol amendment, both studies were stopped for efficacy. Thus, the primary analysis population included only patients who, at the time of the interim analysis data cutoff, had the opportunity to reach the test-of-cure visit or were known to not have attained therapeutic success before the test-of-cure visit. In EAGLE-2, 162 (50·6%) of 320 patients assigned gepotidacin and 135 (47·0%) of 287 patients assigned nitrofurantoin had therapeutic success (adjusted difference 4·3%, 95% CI -3·6 to 12·1). In EAGLE-3, 162 (58·5%) of 277 patients assigned gepotidacin and 115 (43·6%) of 264 patients assigned nitrofurantoin had therapeutic success (adjusted difference 14·6%, 95% CI 6·4 to 22·8). Gepotidacin was non-inferior to nitrofurantoin in both studies and superior to nitrofurantoin in EAGLE-3. The most common adverse event with gepotidacin was diarrhoea (observed in 111 [14%] of 766 patients in EAGLE-2 and in 147 [18%] of 804 patients in EAGLE-3), whereas the most common adverse event with nitrofurantoin was nausea (in 29 [4%] of 760 patients in EAGLE-2 and in 35 [4%] of 798 patients in EAGLE-3). Cases were mostly mild or moderate. No life-threatening or fatal events occurred. INTERPRETATION: Gepotidacin is an efficacious oral antibiotic with acceptable safety and tolerability profiles. As a first-in-class investigational oral antibiotic with activity against common uropathogens, including clinically important drug-resistant phenotypes, gepotidacin has the potential to offer substantial benefit to patients. FUNDING: GSK and the US Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority.


Assuntos
Acenaftenos , Compostos Heterocíclicos com 3 Anéis , Nitrofurantoína , Infecções Urinárias , Adulto , Adolescente , Recém-Nascido , Humanos , Feminino , Nitrofurantoína/uso terapêutico , Resultado do Tratamento , Antibacterianos , Infecções Urinárias/tratamento farmacológico , Pesquisa , Método Duplo-Cego
17.
Urol Int ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316122

RESUMO

INTRODUCTION: Symptomatic lymphocele remains a relevant complication after pelvic tumor surgery. This study aims to investigate how the number of lymph nodes removed may influence postoperative outcomes, and if it increases the probability of detecting lymph node metastasis. METHODS: The study included 500 patients who underwent RARP including lymphadenectomy performed by a single surgeon. Patients were divided into two groups: Group 1 consisted of 308 patients with 20 or fewer lymph nodes removed (mean 15), while Group 2 had 192 patients with over 20 nodes removed (mean 27). Perioperative data were analyzed and postoperative outcomes were compared between groups. RESULTS: Overall lymph node metastasis was detected in 17.8% of men. In detail, out of 19.6 lymph nodes removed, an average of 3.14 lymph nodes per patient showed metastasis, with a slightly higher incidence of 19.7% in group 2 compared to 16.5% in group 1, though not statistically significant (p=0.175). The number of lymph nodes metastasis was significantly higher in group 2 patients 3,47 vs. 2,37 in group 1(p=0.048). All complications except symptomatic lymphoceles (p=0.004) were not significantly different between groups. Univariate linear regression analysis revealed no correlation between the number of removed lymph nodes and symptomatic lymphocele. However, it did correlate with catheter days and readmissions. CONCLUSION: A correlation may exist between the number of lymph nodes removed during RARP and an increased incidence of complications, particularly symptomatic lymphocele. A more extensive PLND may result in prolonged catheter days and increased readmissions. With the increased extent of pelvic lymphadenectomy, the probability of detecting lymphogenic metastasis rises. The diagnostic value of PLND is well established. Further randomized trials are needed to weigh its necessity and extent.

18.
Eur Urol Focus ; 10(1): 77-79, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37541917

RESUMO

Although tuberculosis (TB) ranks among the most frequent infectious diseases worldwide, one of its extrapulmonary (EP) manifestations, genitourinary (GU) TB, is often underestimated by urologists, particularly in areas such as Europe where TB is not endemic. The aim of this review is to give urologists a concise overview of GUTB as a supplement to the more comprehensive European Association of Urology 2023 update on urological infections guidelines. EPTB can develop in 16% of TB cases. GUTB accounts for 4.6% of EPTB and is often asymptomatic or nonspecific, so it can be confused with other urogenital diseases. GUTB can be highly destructive, leading to failure of urogenital organs. Diagnosis is via microbiological, molecular, and histological testing for urine, genital secretions, or genitourinary tissue, supported by imaging. A 6-mo combinational medical regimen is the first-line treatment for GUTB. However, surgical interventions are also frequently required for the treatment of GUTB complications. Therefore, it is important to keep GUTB in mind for differential diagnosis. PATIENT SUMMARY: We reviewed scientific studies on the occurrence, diagnosis, and treatment of tuberculosis in the genitourinary tract. Our aim is to raise awareness among urologists from countries where this disease does not occur frequently, as urogenital tuberculosis can occur without any symptoms or with unspecific symptoms that can be confused with other diseases.


Assuntos
Tuberculose Urogenital , Tuberculose , Urologia , Humanos , Urologistas , Tuberculose Urogenital/terapia , Tuberculose Urogenital/cirurgia , Tuberculose/diagnóstico , Diagnóstico Diferencial
19.
Nephrol Dial Transplant ; 39(4): 581-588, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891013

RESUMO

Antimicrobial resistance (AMR) has emerged as a significant global healthcare problem. Antibiotic use has accelerated the physiologic process of AMR, particularly in Gram-negative pathogens. Urinary tract infections (UTIs) are predominantly of a Gram-negative nature. Uropathogens are evolutionarily highly adapted and selected strains with specific virulence factors, suggesting common mechanisms in how bacterial cells acquire virulence and AMR factors. The simultaneous increase in resistance and virulence is a complex and context-dependent phenomenon. Among known AMR mechanisms, the plenitude of different ß-lactamases is especially prominent. The risk for AMR in UTIs varies in different patient populations. A history of antibiotic consumption and the physiology of urinary flow are major factors that shape AMR prevalence. The urinary tract is in close crosstalk with the microbiome of other compartments, including the gut and genital tracts. In addition, pharmacokinetic properties and the physiochemical composition of urinary compartments can contribute to the emergence of AMR. Alternatives to antibiotic treatment and a broader approach to address bacterial infections are needed. Among the various alternatives studied, antimicrobial peptides and bacteriophage treatment appear to be highly promising approaches. We herein summarize the present knowledge of clinical and microbiological AMR in UTIs and discuss innovative approaches, namely new risk prediction tools and the use of non-antibiotic approaches to defend against uropathogenic microbes.


Assuntos
Infecções Urinárias , Sistema Urinário , Humanos , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções Urinárias/tratamento farmacológico
20.
Front Immunol ; 14: 1227191, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37790937

RESUMO

Introduction: Streptococcus pneumoniae is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and under infectious conditions. However, the molecular adaptations of AM upon infections with Streptococcus pneumoniae are incompletely resolved. Methods: We used a comparative transcriptomic and proteomic approach to provide novel insights into the cellular mechanism that changes the molecular signature of AM during lung infections. Using a tandem mass spectrometry approach to murine cell-sorted AM, we revealed significant proteomic changes upon lung infection with Streptococcus pneumoniae. Results: AM showed a strong neutrophil-associated proteomic signature, such as expression of CD11b, MPO, neutrophil gelatinases, and elastases, which was associated with phagocytosis of recruited neutrophils. Transcriptomic analysis indicated intrinsic expression of CD11b by AM. Moreover, comparative transcriptomic and proteomic profiling identified CD11b as the central molecular hub in AM, which influenced neutrophil recruitment, activation, and migration. Discussion: In conclusion, our study provides novel insights into the intrinsic molecular adaptations of AM upon lung infection with Streptococcus pneumoniae and reveals profound alterations critical for effective antimicrobial immunity.


Assuntos
Antígeno CD11b , Pneumonia Pneumocócica , Animais , Camundongos , Integrinas , Pulmão , Macrófagos Alveolares , Proteômica , Streptococcus pneumoniae , Transcriptoma
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