Fatores de risco para a infeção associada a cateter venoso central – revisão sistemática

O uso de Cateter Venoso Central é apontado como um importante fator de risco para infeção, aumentando a mortalidade e morbilidade, bem como o período de internamento e os custos associados. Identificar os fatores de risco para a infeção associados à utilização de Cateter Venoso Central em doentes adultos hospitalizados. Foram selecionados 30 artigos através dos descritores, Cateteres Venosos Centrais, Infeções Relacionadas com Cateter e Fatores de Risco, através da consulta electrónica nas bases de dados PubMed, Lilacs e Scielo. Definimos como critérios de inclusão, estudos publicados entre 2007 e 2013, realizados em adultos hospitalizados com utilização de Cateter Venoso Central, estarem publicados em língua portuguesa e em revistas com indexação ISI. Obtivemos uma total de 8 publicações tendo rejeitado 22 por não cumprirem os critérios de inclusão. Do total dos 8 estudos analisados, 62,5% referem como fatores de risco para a infeção do Cateter Venoso Central, o local de inserção, sendo a veia femoral e a jugular referidas em 37% dos estudos como os locais mais prevalentes. O tempo de tempo de permanência do Cateter foi outro dos fatores de risco encontrado em 75% dos estudos, sendo que a grande maioria verificou correlação positiva do risco de infeção do Cateter com o número de dias de permanência. O maior número de lúmenes do Cateter foi referido também como fator de risco em 50% dos estudos e em igual proporção a falta de cuidados na manutenção do Cateter, devido a uma má manipulação do mesmo aumentando o risco de infeção. Igualmente a situação clínica do doente constituiu um fator de risco em 50% dos estudos, sendo que a gravidade da história clínica elevou o risco de infeção. O aumento do tempo de internamento foi outro fator de risco referido em 12,5% dos estudos. Discussão e Conclusão: Tendo em conta o elevado número de fatores de risco associados às infeções do Cateter Venoso Central, torna-se fundamental ter conhecimento dos mesmos com vista à sua redução, pois é necessária a implementação de medidas de controlo de infeção por parte dos profissionais de saúde, quer no momento da sua inserção quer no seu manuseamento de forma a prevenir esta infeção

Reproducibility Analysis Of The Stability And Treatment Of Vertebral Metastatic Lesions

Objectives: To investigate the reproducibility among spine surgeons in defining the treatment of vertebral metastatic lesions, taking into account the mechanical stability of injuries. Methods: Twenty cases of isolated vertebral metastatic lesions were presented to ten experts. Their opinion was then asked about the stability of the lesion, as well as their treatment option. Results: The interobserver Kappa coefficient obtained both for stability analysis as to the decision of the treatment was poor (0.334 and 0.248, respectively). Conclusions: Poor interobserver reproducibility was observed in deciding the treatment of vertebral metastatic lesions when considering the stability of the lesions.133232234American Cancer Society, (2007) Cancer Facts and Figures, , Atlanta: American Cancer SocietyNewman, C.B., Keshavarzi, S., Aryan, H.E., En bloc sacrectomy and reconstruction technique modification for pelvic fixation (2009) Surg Neurol, 72 (6), pp. 752-756Harrington, K.D., Current concepts review: Metastatic disease of the spine (1986) J Bone Joint Surg Am, 68 (7), pp. 1110-1115Gasbarrini, A., Cappuccio, M., Mirabile, L., Bandiera, S., Terzi, S., Barbanti Bròdano, G., Spinal metastases: Treatment evaluation algorithm (2004) Eur Rev Med Pharmacol Sci, 8 (6), pp. 265-274Bilsky, M., Smith, M., Surgical approach to epidural spinal cord compression (2006) Hematol Oncol Clin North Am, 20 (6), pp. 1307-1317Weber, M.H., Burch, S., Buckley, J., Schmidt, M.H., Fehlings, M.G., Vrionis, F.D., Instability and impending instability of the thoracolumbar spine in patients with spinal metastases: A systematic review (2011) Int J Oncol, 38 (1), pp. 5-12Tokuhashi, Y., Kawano, H., Ohsaka, S., Matsuzaki, H., Toriyama, S., A scoring system for preoperative evaluation of the prognosis of metastatic spine tumor (a preliminary report) (1989) Nihon Seikeigeka Gakkai Zasshi, 63 (5), pp. 482-489Tokuhashi, Y., Matsuzaki, H., Toriyama, S., Kawano, H., Ohsaka, S., Scoring system for the preoperative evaluation of metastatic spine tumor prognosis (1990) Spine (Phila Pa 1976), 15 (11), pp. 1110-1113Tomita, K., Kawahara, N., Baba, H., Tsuchiya, H., Fujita, T., Toribatake, Y., Total em bloc spondylectomy. A new surgical technique for primary malignant vertebral tumors (1997) Spine (Phila Pa 1976), 22 (3), pp. 324-333Tomita, K., Kawahara, N., Kobayashi, T., Yoshida, A., Murakami, H., Akamaru, T., Surgical strategy for spinal metastases (2001) Spine (Phila Pa 1976), 26 (3), pp. 298-306Fisher, C.G., DiPaola, C.P., Ryken, T.C., Bilsky, M.H., Shaffrey, C.I., Berven, S.H., A novel classification system for spinal instability in neoplastic disease: An evidence-based approach and expert consensus from the Spine Oncology Study Group (2010) Spine (Phila Pa 1976), 35 (22), pp. E1221-E1229Fourney, D.R., Frangou, E.M., Ryken, T.C., Dipaola, C.P., Shaffrey, C.I., Berven, S.H., Spinal instability neoplastic score: An analysis of reliability and validity from the spine oncology study group (2011) J Clin Oncol, 29 (22), pp. 3072-307

Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and ‘tumor spread through air spaces’ were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk

The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer

Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population. Moreover, we demonstrate that Vδ1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral Vδ1 T cells possessed stem-like features and were skewed toward cytolysis and helper T cell type 1 function, akin to intratumoral natural killer and CD8+ T cells considered beneficial to the patient. Indeed, ongoing remission post-surgery was significantly associated with the numbers of CD45RA−CD27− effector memory Vδ1 T cells in tumors and, most strikingly, with the numbers of CD103+ tissue-resident Vδ1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating Vδ1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer

Lung adenocarcinoma promotion by air pollutants

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden

Laxoprofen Sodium In The Treatment Of Lumbar Pain. A Bibliographic Revision [loxoprofeno Sodico No Tratamento Das Lombalgias. Revisao Bibliografica]

A bibliographic revision of 1618 patients from 105 orthopoedic institutions on the action of loxoprofen Na in the treatment of lumbar pain was conducted. The drug can be considered an efficient and safe treatment with a low rate of adverse events.574298302Yoshioka, Y., Clinical Study of CS-600( Loxoprofen Sodium) on Low Back Pain (1984) Jpn Pharmacol Ther, 12 (2), pp. 345-357Nagata, K., Estudo da eficácia e segurança do Loxonin® na lombalgia do idoso (1990) Progress in Medicine, 10 (10), pp. 2611-2620Hirohata, K., CS-600 na dor lombar, avaliação clinica do Loxoprofeno sódico (1985) Progress in Medicine, 5 (5), pp. 155-173Noguchi, K., Study of Loxonin® for senile lumbago (1993) Progress in Medicine, 13 (1), pp. 77-91Yamaga, S., Study of the safety and effectiveness of Loxonin® on lumbago (1990) Progress in Medicine, 10 (4), pp. 827-834Nishio, A., Estudo clínico de Loxoprofeno Sódico nas doenças lombálgicas (1993) Progress in Medicine, 13 (4), pp. 733-746Shimatsu, A., Evaluation on effectiveness and safety of de Loxonin® for lumbago (1990) Progress in Medicine, 10 (9), pp. 2217-2227Ushijima, M., Study on efficacy and safety of Loxonin® for lumbago (1990) Progress in Medicine, 10 (2), pp. 403-412Kanemitsu, S., Study of effectiveness and safety of Loxonin® for lumbago (1990) Geriatric Medicine, 28, pp. 1851-1862Ohta, N., Kawaji, W., Clinical findings on CS-600 (Loxoprofen sodium) in the treatment of low back pain, cervicobrachial syndrome and periarthritis of the shoulder (1984) Journal of New Remedies & Clinics, 33 (11), pp. 1535-1546Funakoshi, M., Study on availability of the Loxonin® for low back pain (1993) Progress in Medicine, 13 (1), pp. 67-7