Knowledge of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization is important to prevent nosocomial spread but also to start prompt adequate antibiotic therapy in patients with suspicion ...of infection. However, few studies have examined the incidence and risk factors for CR-KP bloodstream infection (BSI) among rectal carriers. To identify risk factors for CR-KP BSI among carriers, we performed a multicentre prospective matched case–control study of all adult CR-KP rectal carriers hospitalized in five tertiary teaching hospitals in Italy over a 2-year period. Carriers who developed CR-KP BSI were compared with those who did not develop subsequent BSI. Overall, 143 CR-KP BSIs were compared with 572 controls without a documented infection during their hospitalization. Multivariate analysis revealed that admission to the Intensive Care Unit (ICU) (OR, 1.65; 95% CI, 1.05–2.59; p 0.03), abdominal invasive procedure (OR, 1.87; 95% CI, 1.16–3.04; p 0.01), chemotherapy/radiation therapy (OR, 3.07; 95% CI, 1.78–5.29; p <0.0001), and number of additional colonization sites (OR, 3.37 per site; 95% CI, 2.56–4.43; p <0.0001) were independent risk factors for CR-KP BSI development among CR-KP rectal carriers. A CR-KP BSI risk score ranging from 0 to 28 was developed based on these four independent variables. At a cut-off of ≥2 the model exhibited a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 42%, 29% and 93%, respectively. Colonization at multiple sites with CR-KP was the strongest predictor of BSI development in our large cohort of CR-KP rectal carriers.
Introduction: the purpose of this retrospective multicenter study was to assess whether the risk of developing bloodstream infections (BSI) due to carbapenem-resistant
Klebsiella pneumoniae
(CRKP) in ...colonized patients is influenced by the occurrence of BSI due to other pathogens. Methods: from January 2012 to March 2014, all patients with at least one rectal swab positive for CRKP and at least 30 days of previous hospital stay were included in the study. The primary outcome measure was CRKP BSI, defined as a time-to-event endpoint. The role of potential predictors was evaluated through univariable and multivariable Cox regression analyses, considering previous BSI as a time-dependent variable. Results: during the study period, 353 patients met the inclusion criteria. Thirty-seven developed a CRKP BSI (11%). A higher incidence of CRKP BSI was observed in presence rather than in absence of previous BSI. In the final multivariable model of risk factors for CRKP BSI, multisite colonization (hazard ratio HR 13.73, 95% confidence intervals CI 3.29–57.32,
p
< 0.001), ICU stay (HR 3.14, 95% CI 1.19–8.31,
p
= 0.021), and previous BSI (
p
= 0.026, with the overall effect being mainly due to
Enterococcus
spp. BSI vs absence of BSI, HR 6.62, 95% CI 2.11–20.79) were associated with the development of CRKP BSI, while an inverse association was observed for age (HR 0.98, 95% CI 0.95–1.00,
p
= 0.027). Conclusions: previous BSI due to other pathogens were associated with an increased risk of CRKP BSI that was independent of other factors in colonized patients with prolonged hospital exposure.
In a prospective cohort of 18 patients treated with boceprevir, we examined the role of boceprevir plasma concentration at the onset of breakthrough during the treatment. Nine patients experienced ...breakthrough during therapy. The resistance patterns were as follows: S122S/R, I132V, T54A/I132V, V156S/I170A, V36M/T54S/R155K, V36M/R155K and T54/R155K. Boceprevir-S isomer (SCH 534128) median concentration in patients with breakthrough was 48.3 ng/mL (interquartile range 43–58 ng/mL); in others, it was significantly (p 0.019) higher: 151 ng/mL. Low boceprevir plasma concentration can lead to virologic resistance; therapeutic drug monitoring should be used to prevent the onset of viral breakthrough during triple-regimen therapy with boceprevir.
Summary
An important prerequisite for a conservation programme is a comprehensive description of genetic diversity. The aim of this study was to use anonymous genetic markers to assess the between‐ ...and the within‐population components of genetic diversity for European pig breeds at the scale of the whole continent using microsatellites. Fifty‐eight European pig breeds and lines were analysed including local breeds, national varieties of international breeds and commercial lines. A sample of the Chinese Meishan breed was also included. Eleven additional breeds from a previous project were added for some analyses. Approximately 50 individuals per breed were genotyped for a maximum of 50 microsatellite loci. Substantial within‐breed variability was observed, with the average expected heterozygosity and observed number of alleles per locus being 0.56 range 0.43–0.68 and 4.5 respectively. Genotypic frequencies departed from Hardy–Weinberg expectations (P < 0.01) in 15 European populations, with an excess of homozygotes in 12 of them. The European breeds were on average genetically very distinct, with a Wright FST index value of 0.21. The Neighbour‐Joining tree drawn from the Reynolds distances among the breeds showed that the national varieties of major breeds and the commercial lines were mostly clustered around their breeds of reference (Duroc, Hampshire, Landrace, Large White and Piétrain). In contrast, local breeds, with the exception of the Iberian breeds, exhibited a star‐like topology. The results are discussed in the light of various forces, which may have driven the recent evolution of European pig breeds. This study has consequences for the interpretation of biodiversity results and will be of importance for future conservation programmes.
In this work, we present WALK‐MAN, a humanoid platform that has been developed to operate in realistic unstructured environment, and demonstrate new skills including powerful manipulation, robust ...balanced locomotion, high‐strength capabilities, and physical sturdiness. To enable these capabilities, WALK‐MAN design and actuation are based on the most recent advancements of series elastic actuator drives with unique performance features that differentiate the robot from previous state‐of‐the‐art compliant actuated robots. Physical interaction performance is benefited by both active and passive adaptation, thanks to WALK‐MAN actuation that combines customized high‐performance modules with tuned torque/velocity curves and transmission elasticity for high‐speed adaptation response and motion reactions to disturbances. WALK‐MAN design also includes innovative design optimization features that consider the selection of kinematic structure and the placement of the actuators with the body structure to maximize the robot performance. Physical robustness is ensured with the integration of elastic transmission, proprioceptive sensing, and control. The WALK‐MAN hardware was designed and built in 11 months, and the prototype of the robot was ready four months before DARPA Robotics Challenge (DRC) Finals. The motion generation of WALK‐MAN is based on the unified motion‐generation framework of whole‐body locomotion and manipulation (termed loco‐manipulation). WALK‐MAN is able to execute simple loco‐manipulation behaviors synthesized by combining different primitives defining the behavior of the center of gravity, the motion of the hands, legs, and head, the body attitude and posture, and the constrained body parts such as joint limits and contacts. The motion‐generation framework including the specific motion modules and software architecture is discussed in detail. A rich perception system allows the robot to perceive and generate 3D representations of the environment as well as detect contacts and sense physical interaction force and moments. The operator station that pilots use to control the robot provides a rich pilot interface with different control modes and a number of teleoperated or semiautonomous command features. The capability of the robot and the performance of the individual motion control and perception modules were validated during the DRC in which the robot was able to demonstrate exceptional physical resilience and execute some of the tasks during the competition.
In a prospective cohort of 18 patients treated with boceprevir, we examined the role of boceprevir plasma concentration at the onset of breakthrough during the treatment. Nine patients experienced ...breakthrough during therapy. The resistance patterns were as follows: S122S/R, I132V, T54A/I132V, V156S/I170A, V36M/T54S/R155K, V36M/R155K and T54/R155K. Boceprevir-S isomer (SCH 534128) median concentration in patients with breakthrough was 48.3 ng/mL (interquartile range 43-58 ng/mL); in others, it was significantly (p 0.019) higher: 151 ng/mL. Low boceprevir plasma concentration can lead to virologic resistance; therapeutic drug monitoring should be used to prevent the onset of viral breakthrough during triple-regimen therapy with boceprevir.
Background: Bone scanning (BS), liver ultrasonography (LUS) and chest radiography (CXR) are commonly used in patients with newly diagnosed breast cancer as part of baseline staging. However, in the ...absence of symptomatic disease, the usefulness of this routine diagnostic work-up is not evidence-based. Methods: We selected the study sample from 516 consecutive patients with newly diagnosed invasive breast cancer. For each diagnostic test (BS, LUS, CXR), we analyzed the prevalence defined as the number of patients with diagnosis of metastatic disease after an imaging technique divided by the total number of patients tested. In addition, sensitivity and specificity were calculated. Initial suspicion was confirmed by other independent tests (bone X-ray, computerized tomography scan, magnetic resonance imaging) in order to identify ‘true’ positive diagnoses. Results: At baseline, BS was carried out in 412 patients, LUS in 412 patients and CXR in 428 patients. Thirty-three patients were correctly diagnosed by the initial staging investigations as having metastatic disease (true positive cases). BS detected skeletal metastases in 6.31% of patients, LUS detected liver metastases in 0.72% of patients and CXR detected lung metastases in 0.93% of patients. Before imaging tests, all patients with either LUS or CXR evidence of metastases were previously classified as having stage III disease. On the other hand, only 26.9% of bone metastases were detected in patients with stage III. Accordingly, the detection rate in stage III patients was 14%, 5.6% and 7.2%, respectively for BS, LUS and CXR. Conclusions: These findings indicate that a complete diagnostic work-up to detect metastases is unnecessary in the majority of patients with newly diagnosed breast cancer, whereas it may be indicated for specific patient categories such as those with stage III disease.
Background: The occurrence of spontaneous tumors in pet animals has been estimated in a few European and North American veterinary cancer registries with dissimilar methodologies and variable ...reference populations.
Objectives: The Animal Tumor Registry (ATR) of Genoa, Italy, was established in 1985 with the aim of estimating the occurrence of spontaneous tumors in dogs.
Methods: Six thousand seven hundred and forty‐three tumor biopsy specimens were received from local veterinarians in the Municipality of Genoa between 1985 and 2002. Three thousand and three hundred and three (48.9%) biopsy specimen samples were diagnosed as cancer and were coded according to the International Statistical Classification of Diseases (ICD‐9).
Results: Mammary cancer was the most frequently diagnosed cancer in female dogs, accounting for 70% of all cancer cases. Incidence of all cancers was 99.3 per 100,000 dog‐years (95% CI: 93.6–105.1) in male dogs and 272.1 (95% CI: 260.7–283.6) in female dogs. The highest incidence rates were detected for mammary cancer (IR = 191.8, 95% CI: 182.2–201.4) and for non‐Hodgkin's lymphoma (IR = 22.9, 95% CI: 19.7–26.5) in bitches and for non‐Hodgkin's lymphoma (IR = 19.9, 95% CI: 17.4–22.7) and skin cancer (IR = 19.1, 95% CI: 16.6–21.8) in male dogs. All cancer IR increased with age ranging between 23.7 (95% CI: 18.4–30.1) and 763.2 (95% CI: 700.4–830.1) in bitches and between 16.5 (95% CI: 12.8–21.1) and 237.6 (95% CI: 209.1–269.0) in male dogs aged ≤3 years and >9–11 years.
Conclusion: This study summarizes the work done by the ATR of Genoa, Italy, between 1985 and 2002. All cancer incidence was 3 times higher in female than in male dogs, a difference explained by the high rate of mammary cancer observed in bitches. Because a biopsy specimen was required to make a cancer diagnosis, cancer rates for internal organs cancers, such as respiratory and digestive tract cancers may have been underestimated in the study population.
Background
We report the final results of the randomized phase 2 FIGHT trial that evaluated bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), ...plus mFOLFOX6 in patients with FGFR2b-positive (2 + /3 + membranous staining by immunohistochemistry), HER-2–negative gastric or gastroesophageal junction cancer (GC).
Methods
Patients received bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months.
Results
In the bemarituzumab-mFOLFOX6 (N = 77) and placebo-mFOLFOX6 (N = 78) arms, respectively, 59.7% and 66.7% of patients were FGFR2b-positive in ≥ 10% of tumor cells. The median PFS (95% confidence interval CI) was 9.5 months (7.3–13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7–8.4) with placebo-mFOLFOX6 (hazard ratio HR, 0.72; 95% CI 0.49–1.08); median OS (95% CI) was 19.2 (13.6–24.2) and 13.5 (9.3–15.9) months, respectively (HR 0.77; 95% CI 0.52–1.14). Observed efficacy in FGFR2b-positive GC in ≥ 10% of tumor cells was: PFS: HR 0.43 (95% CI 0.26–0.73); OS: HR 0.52 (95% CI 0.31–0.85). No new safety findings were reported.
Conclusions
In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626).
Clinical trial registration
NCT03694522.
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