Biological and prognostic implications of biopsy upgrading for high-grade upper tract urothelial carcinoma at nephroureterectomy

Objectives Technical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated. Methods Patients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low-grade on URS biopsy) versus same grade (high-grade on URS biopsy) for high-grade UTUC tumors on radical nephroureterectomy (RNU) specimens. Results This study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy-based low- and high-grade tumors, respectively. Median follow-up was 27.3 months. Patients with high-grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high-grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10-2.75; p = 0.018), cancer-specific (HR 1.94; 95% CI, 1.07-3.52; p = 0.03), and recurrence-free survival (HR 1.80; 95% CI, 1.13-2.87; p = 0.013). In subgroup analyses of patients with pT2-T4 and/or positive LN, its significant association retained. Furthermore, high-grade biopsy in clinically non-muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (>= pT2) compared to low-grade biopsy. Conclusions High tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low-grade UTUC that becomes upgraded to high-grade might carry a better prognosis than high-grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high-grade on RNU

A pristine record of outer Solar System materials from asteroid Ryugu’s returned sample

Volatile and organic-rich C-type asteroids may have been one of the main sources of Earth’s water. Our best insight into their chemistry is currently provided by carbonaceous chondritic meteorites, but the meteorite record is biased: only the strongest types survive atmospheric entry and are then modified by interaction with the terrestrial environment. Here we present the results of a detailed bulk and microanalytical study of pristine Ryugu particles, brought to Earth by the Hayabusa2 spacecraft. Ryugu particles display a close compositional match with the chemically unfractionated, but aqueously altered, CI (Ivuna-type) chondrites, which are widely used as a proxy for the bulk Solar System composition. The sample shows an intricate spatial relationship between aliphatic-rich organics and phyllosilicates and indicates maximum temperatures of ~30 °C during aqueous alteration. We find that heavy hydrogen and nitrogen abundances are consistent with an outer Solar System origin. Ryugu particles are the most uncontaminated and unfractionated extraterrestrial materials studied so far, and provide the best available match to the bulk Solar System composition

The impact of infectious disease consultation in candidemia in a tertiary care hospital in Japan over 12 years.

BackgroundCandidemia is one of the major causes of morbidity and mortality as a hospital acquired infection. Infectious diseases consultation (IDC) might be beneficial to improve candidemia outcomes; however, only limited data from short periods of time are available thus far.MethodsAn observational study of all candidemia patients at a large tertiary care hospital between 2002 and 2013 was conducted. A candidemia episode was defined as ≥ 1 positive result for Candida spp. in blood culture. Patients who died or transferred to another hospital within two days after their first positive blood culture were excluded. Independent risk factors for 30-day mortality were determined.ResultsAmong 275 patients with 283 episodes of candidemia, 194 (68.6%) were male, and the mean age was 70.0 ± 15.8 years. Central line-associated bloodstream infections, peripheral line-associated bloodstream infections, intra-abdominal infection, and unknown source comprised 220 (77.7%), 35 (12.4%), 13 (4.7%), and 15 (5.3%) episodes, respectively. A total of 126 patients (44.5%) received IDC. Factors independently associated with 30-day mortality in patients with candidemia were urinary catheters use (adjusted hazard ratio [HR] = 2.94; 95% confidence interval [CI] = 1.48-5.87; P = 0.002) and severe sepsis/septic shock (adjusted HR = 2.10; 95% CI = 1.20-3.65; P = 0.009). IDC was associated with a 46% reduction in 30-day mortality (adjusted HR = 0.54; 95% CI = 0.32-0.90; P = 0.017).ConclusionIDC was independently associated with a reduction in 30-day mortality. Only 44.5% of patients with candidemia in this cohort received IDC. Routine IDC should be actively considered for patients with candidemia

Epidemiology of Blood Stream Infection due to Candida Species in a Tertiary Care Hospital in Japan over 12 Years: Importance of Peripheral Line-Associated Candidemia.

Candidemia is an important cause of mortality in healthcare settings. Peripheral lines are a source of candidemia, yet few studies have reported on the clinico-epidemiological features of candidemia due to peripheral-line associated blood stream infection (PLABSI).We conducted a single-centre retrospective cohort study of all patients with candidemia between 2002 and 2013. PLABSI was defined as the presence of at least one of the following: the presence of phlebitis or the resolution of clinical symptoms after peripheral-line withdrawal, with careful exclusion of an alternative explanation for bacteraemia. We described the epidemiology of candidemia and assessed predictive factors of PLABSI due to Candida spp., peripheral line-associated candidemia (PLAC), compared with non-PLAC.A total of 301 episodes of candidemia, including 37 of PLAC, were diagnosed during the study period. Central-line associated blood stream infection, intra-abdominal infection, and infection of unknown source accounted for the remaining 233, 14, and 17 cases, respectively. The overall incidence rate of candidemia was 0.11/1000 patient-days. In multivariate analysis, cephalosporin exposure (odds ratio [OR] = 2.22, 95% CI 1.04-4.77), polymicrobial bacteraemia/fungaemia (OR = 2.87, 95% CI 1.02-8.10), and ID specialist consultation (OR = 2.40, 95% CI 1.13-5.13) were identified as independent predictors of PLAC. Although non-PLAC had a higher mortality, the length of hospital stay after candidemia was similar between the two groups and candidemia duration was longer in the PLAC group.PLACs are an important cause of candidemia in hospitalized patients. Appropriate identification and management of PLAC are crucial