Although Haemophilus influenzae is a common etiologic agent of pneumonia in patients infected with human immunodeficiency virus (HIV), the characteristics of this pneumonia have not been adequately ...assessed. We have prospectively studied features of H. influenzae pneumonia in 26 consecutive HIV-infected inpatients. Most of these patients were severely immunosuppressed; 73.1% had a CD4+ cell count <100/µL. A subacute clinical presentation was observed in 27% of the patients and was associated with a higher degree of immunosuppression (P=.04). Bilateral lung infiltrates were noted radiographically in 57.7% of the cases. The mortality attributable to H. influenzae pneumonia was 11.5%. Thus, pneumonia caused by H. influenzae affects mainly patients with advanced HIV disease, and since its clinical and radiological features may be diverse, this etiology should be considered when pneumonia occurs in patients with advanced HIV infection. The mortality rate associated with H. influenzae pneumonia is not higher than that occurring in the general population.
Resumen: Objetivo: Evaluar la relación existente entre la cultura de seguridad y la satisfacción laboral en un hospital de media-larga estancia, evidenciar las relaciones existentes entre las ...dimensiones que definen ambos constructos e identificar las dimensiones con mayor impacto sobre las dos variables. Métodos: Estudio transversal realizado en 2015, utilizando la Encuesta de Satisfacción Laboral del Servicio Vasco de Salud y la versión española del cuestionario Hospital Survey on Patient Safety (Agency for Healthcare Research and Quality). Variables resultado: alta satisfacción laboral y alta seguridad percibida (puntuación igual o superior al percentil 75). Variables predictoras: características sociodemográficas y percepción de las dimensiones evaluadas. La asociación entre variables se cuantificó mediante odds ratio (OR) ajustada y su intervalo de confianza del 95%. Resultados: La satisfacción laboral media fue de 7,21 (desviación estándar DE: 2,01) y la seguridad percibida fue de 7,48 (DE: 1,98). El percentil 75 de la distribución en ambos casos fue 9. Las variables sociodemográficas presentaron escasa significación, mientras que una buena percepción de muchas de las dimensiones consideradas sí se asoció a las variables resultado. En el análisis de datos se obtuvieron múltiples correlaciones significativas y relaciones cruzadas entre las dimensiones que definen ambos constructos, así como entre el grado de satisfacción de las dimensiones consideradas y las variables resultado. Conclusión: Los resultados evidencian que existe relación entre la satisfacción laboral y la cultura de seguridad, y cuantifican el grado de asociación entre las variables estudiadas. La OR ajustada identifica las variables más fuertemente asociadas con el efecto y ayuda a seleccionar áreas de mejora. Abstract: Objective: To evaluate the relationship between safety culture and job satisfaction in a medium-stay hospital, showing the relationships between the dimensions that define both constructs and identifying the dimensions with the greatest impact on both variables. Methods: Cross-sectional study conducted in 2015, using the Basque Health Service Job Satisfaction Survey and the Spanish version of the «Hospital Survey on Patient Safety» questionnaire (Agency for Healthcare Research and Quality). Result Variables: high job satisfaction and high degree of perceived security (score ≥75th percentile). Predictor variables: socio-demographic characteristics and perception of the evaluated dimensions. The association between variables was quantified by adjusted odds ratio (OR) and the 95% confidence interval. Results: The mean job satisfaction was 7.21 (standard deviation SD: 2.01) and the mean of perceived safety was 7.48 (SD = 1.98). The 75th percentile of the distribution in both cases was 9. The socio-demographic variables had little significance, while a positive perception of many of the considered dimensions, was associated with high perception of the result variables. In the data analysis were obtained multiple significant correlations and cross-relations between the dimensions that define both constructs, as well as between the degree of satisfaction of the dimensions considered and the outcome variables. Conclusion: The results obtained evidenced the relationship between job satisfaction and safety culture and quantify the association degree between the studied variables. The adjusted OR identifies the variables most strongly associated with the effect and helps to select improvement areas. Palabras clave: Satisfacción laboral, Cultura de seguridad, Seguridad del paciente, Organizaciones sanitarias, Keywords: Job satisfaction, Safety culture, Patient safety, Health care organizations
NIH sponsored a meeting of medical and veterinary pathologists with mammary gland expertise in Annapolis in March 1999. Rapid development of mouse mammary models has accentuated the need for ...definitions of the mammary lesions in genetically engineered mice (GEM) and to assess their usefulness as models of human breast disease. The panel of nine pathologists independently reviewed material representing over 90% of the published systems. The GEM tumors were found to have: (1) phenotypes similar to those of non-GEM; (2) signature phenotypes specific to the transgene; and (3) some morphological similarities to the human disease. The current mouse mammary and human breast tumor classifications describe the majority of GEM lesions but unique morphologic lesions are found in many GEM. Since little information is available on the natural history of GEM lesions, a simple morphologic nomenclature is proposed that allows direct comparisons between models. Future progress requires rigorous application of guidelines covering pathologic examination of the mammary gland and the whole animal. Since the phenotype of the lesions is an essential component of their molecular pathology, funding agencies should adopt policies ensuring careful morphological evaluation of any funded research involving animal models. A pathologist should be part of each research team.
Objectives
To evaluate if computer-aided diagnosis (CAD) prior to prostate multi-parametric MRI (mpMRI) can improve sensitivity and agreement between radiologists.
Methods
Nine radiologists (three ...each high, intermediate, low experience) from eight institutions participated. A total of 163 patients with 3-T mpMRI from 4/2012 to 6/2015 were included: 110 cancer patients with prostatectomy after mpMRI, 53 patients with no lesions on mpMRI and negative TRUS-guided biopsy. Readers were blinded to all outcomes and detected lesions per PI-RADSv2 on mpMRI. After 5 weeks, readers re-evaluated patients using CAD to detect lesions. Prostatectomy specimens registered to MRI were ground truth with index lesions defined on pathology. Sensitivity, specificity and agreement were calculated per patient, lesion level and zone—peripheral (PZ) and transition (TZ).
Results
Index lesion sensitivity was 78.2% for mpMRI alone and 86.3% for CAD-assisted mpMRI (
p
= 0.013). Sensitivity was comparable for TZ lesions (78.7% vs 78.1%;
p
= 0.929); CAD improved PZ lesion sensitivity (84% vs 94%;
p
= 0.003). Improved sensitivity came from lesions scored PI-RADS < 3 as index lesion sensitivity was comparable at PI-RADS ≥ 3 (77.6% vs 78.1%;
p
= 0.859). Per patient specificity was 57.1% for CAD and 70.4% for mpMRI (
p
= 0.003). CAD improved agreement between all readers (56.9% vs 71.8%;
p
< 0.001).
Conclusions
CAD-assisted mpMRI improved sensitivity and agreement, but decreased specificity, between radiologists of varying experience.
Key Points
• Computer-aided diagnosis (CAD) assists clinicians in detecting prostate cancer on MRI.
• CAD assistance improves agreement between radiologists in detecting prostate cancer lesions.
• However, this CAD system induces more false positives, particularly for less-experienced clinicians and in the transition zone.
• CAD assists radiologists in detecting cancer missed on MRI, suggesting a path for improved diagnostic confidence.
Spatial heterogeneity in medulloblastoma Morrissy, A Sorana; Cavalli, Florence M G; Remke, Marc ...
Nature genetics,
05/2017, Letnik:
49, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Spatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of ...targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor, which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.
Papillary renal-cell carcinomas account for 15 to 20% of kidney cancers. Type 1, which is often multifocal and more indolent, was associated with mutations in
MET
. Type 2, which is more ...heterogeneous and aggressive, was associated with activation of the NRF2-ARE pathway.
Kidney cancer, or renal-cell carcinoma, is not a single disease but is made up of various types of cancer that are characterized by different genetic drivers; each type has distinct histologic features and a distinct clinical course and response to therapy.
1
,
2
Papillary renal-cell carcinoma, which accounts for 15 to 20% of kidney cancers, is a heterogeneous disease with histologic subtypes and variations in both disease progression and patient outcomes. Papillary renal-cell carcinoma has two main subtypes: type 1, which is often multifocal, is characterized by papillae and tubular structures covered with small cells containing basophilic cytoplasm and small, uniform, . . .
Little is known about the risk factors of colectomy in patients with ulcerative colitis (UC) under thiopurine treatment. The aim of the study was to determine the prevalence and the predictive risk ...factors of colectomy in an extensive cohort of patients with UC treated with thiopurines in Spain.
Among 5753 UC patients, we identified those diagnosed between 1980 and 2009 and treated with azathioprine or mercaptopurine (AZA/MP). We analyzed the age at diagnosis, familial history of IBD, extraintestinal manifestations (EIMs), disease extent, smoking status and treatment requirements (AZA/MP, cyclosporine (CsA) or anti-TNFα). Colectomies for dysplasia or cancer were excluded. Survival analysis and Cox proportional hazard regression were performed. Results were reported as hazard ratios (HR) with 95% CI.
Among the 1334 cases included, 119 patients (8.9%) required colectomy after a median time of 26months (IQR 12–42) after AZA/MP initiation. Independent predictors of colectomy were: Extensive UC (HR 1.7, 95% CI: 1.1–2.6), EIMs (HR 1.5, 95% CI: 1.0–2.4), need for antiTNFα (HR 2.3, 95% CI: 1.5–3.4) and need for CsA (HR 2.4, 95% CI: 1.6–3.7). Patients requiring early introduction of AZA/MP had an increased risk of colectomy with a HR of 4.9 (95% CI: 3.2–7.8) when AZA/MP started in the first 33months after UC diagnosis.
Nearly one-tenth of patients with UC under thiopurines require colectomy. Extensive UC, EIMs, need for CsA or anti-TNFα ever and an early need for AZA/MP treatment were associated with a higher risk of colectomy. These risk factors of colectomy could help to stratify risk in further controlled studies in UC.
There is no information about the frequency of liver dysfunction in patients with inflammatory bowel disease (IBD) treated with immunosuppressants and infected with hepatitis B (HBV) and/or C virus ...(HCV).
To assess the influence of immunosuppressants on the course of HBV and HCV infection in IBD.
Patients with IBD with HBV and/or HCV infection from 19 Spanish hospitals were included. Clinical records were reviewed for the type of immunosuppressant used, treatment duration, liver function tests and viral markers before, during and after each immunosuppressant. Logistic and Cox regression analysis were used to identify predictors of outcome.
162 patients were included; 104 had HBV markers (25 HBsAg positive) and 74 had HCV markers (51 HCV-RNA positive), and 16 patients had markers of both infections. Liver dysfunction was observed in 9 of 25 HBsAg positive patients (36%), 6 of whom developed hepatic failure. Liver dysfunction in HCV was observed in 8 of 51 HCV-RNA positive patients (15.7%), and only one developed hepatic failure. The frequency and severity of liver dysfunction was significantly higher in HBV-infected patients than in HCV-infected patients (p=0.045 and p=0.049, respectively). Treatment with ≥2 immunosuppressants was an independent predictor of HBV reactivation (OR 8.75; 95% CI 1.16 to 65.66). The majority of patients without reactivation received only one immunosuppressant for a short period and/or prophylactic antiviral treatment. No definite HBV reactivations were found in anti-HBc positive patients lacking HBsAg.
Liver dysfunction in patients with IBD treated with immunosuppressants is more frequent and severe in those with HBV than in HCV carriers and is associated with combined immunosuppression.
Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, ...risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure.
We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730-rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730-rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided.
Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730-rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval CI = 0.57 to 1.43 cigarettes, P = 5.22 × 10(-6)) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10(-11)). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730-rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42).
Our data show a stronger association of rs1051730-rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure.
The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV ...vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity.
Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders.
For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes.
The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.
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