No germline mutations in supposed tumour suppressor genes SAFB1 and SAFB2 in familial breast cancer with linkage to 19p

<p>Abstract</p> <p>Background</p> <p>The scaffold attachment factor B1 and B2 genes, <it>SAFB1/SAFB2 </it>(both located on chromosome 19p13.3) have recently been suggested as tumour suppressor genes involved in breast cancer development. The assumption was based on functional properties of the two genes and loss of heterozygosity of intragenic markers in breast tumours further strengthened the postulated hypothesis. In addition, linkage studies in Swedish breast cancer families also indicate the presence of a susceptibility gene for breast cancer at the 19p locus. Somatic mutations in <it>SAFB1/SAFB2 </it>have been detected in breast tumours, but to our knowledge no studies on germline mutations have been reported. In this study we investigated the possible involvement of <it>SAFB1/SAFB2 </it>on familiar breast cancer by inherited mutations in either of the two genes.</p> <p>Results</p> <p>Mutation analysis in families showing linkage to the <it>SAFB1/2 </it>locus was performed by DNA sequencing. The complete coding sequence of the two genes <it>SAFB1 </it>and <it>SAFB2 </it>was analyzed in germline DNA from 31 affected women. No missense or frameshift mutations were detected. One polymorphism was found in <it>SAFB1 </it>and eight polymorphisms were detected in <it>SAFB2</it>. MLPA-anlysis showed that both alleles of the two genes were preserved which excludes gene inactivation by large deletions.</p> <p>Conclusion</p> <p><it>SAFB1 </it>and <it>SAFB2 </it>are not likely to be causative of the hereditary breast cancer syndrome in west Swedish breast cancer families.</p

The prognostic impact of the tumour stroma fraction: A machine learning-based analysis in 16 human solid tumour types

Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed.Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns.Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR (95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59 (1.49-8.62)) associations of the tumour stroma fraction with survival.Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance.</p

News journalism : A study of the journalists at the newspaper Aftonbladet opportunities to live up to objective scrutiny of society.

The purpose of this study has been to find out what possibilities the journalists at the newspaper Aftonbladet have to live up to the proposed ideas and values that defines journalism, as well as how these values are presented to the readers. With this as a starting-point we have studied what kind of society Aftonbladet presents to its readers as well as how this society is supposed to work and also what it`s like. To be able to answer this question we have first researched through theories and earlier studies, literature about journalism, media science, semiotics, history and laws. With the help of the investigation we found fitting tools to perform the analysis. With the theory as groundwork we have, through the qualitative approach analyzed seven news articles from seven Aftonbladet newspapers during one week. Our study shows that the Afonbladet’s journalists have not been able to present occurrences in society in a correct and impartial manner - because they exaggerate insignificant details and neglect to show real attention to serious societal structures by using sensationalism, dramatization and a very superficial approach to the stories that they are conveying. We have also been able to establish that it is impossible for journalists to follow up and live up to the ideals of journalism. Not only that, it’s also impossible for them to live up to the ideals that the Aftonbladet as a newspaper has assigned for itself. A probable explanation for this is that the journalism field is characterized by high productivity and demands that the news are supposed to be easily understood and have a specific news value. All of this combined amounts to that a lot of times the journalism becomes accentuated, one sided and simplified, all to lure readers every day because Aftonbladet’s main income comes from single copy sales.

Människans hälsa och ohälsa

Föreliggande uppsatser med det övergripande namnet "Människans hälsa och ohälsa" är utarbetade med utgångspunkt från föredrag vid en KVVS-konferens med samma titel som ägde rum i oktober 2011. I dessa uppsatser behandlas olika problemområden med anknytning till hälsa och ohälsa hos människan. Socialmedicinska frågor som mortalitet, dödsorsaker och morbiditet ges en övergripande beskrivning. Personlig vård inom medicinen kontra regelverk i form av generella riktlinjer beskrivs som delvis kolliderande strategier. Vaccinationsproblematiken diskuteras utifrån erfarenheter från de influensapandemier som drabbar världen med viss regelbundenhet. Smärta och smärtupplevelser behandlas utifrån historiska, diagnostiska och behandlingsmässiga aspekter. Rollen hos brunt fett i vävnader diskuteras utifrån bl.a. nya angreppssätt att komma tillrätta med övervikt och diabetes. Sambanden mellan kostmönster och uppkomst av hjärt-kärlsjukdomar och cancer utreds. En sista uppsats berör fettsyror i bröstmjölk och hur spädbarn tar upp dessa med implikationer för uppkomsten av olika livsstilssjukdomar i vuxen ålder, s.k. epigenetik

Swallowing function in COVID-19 patients after invasive mechanical ventilation

Objective To explore swallowing function and risk factors associated with delayed recovery of swallowing in patients with COVID-19 post–invasive mechanical ventilation using the Functional Oral Intake Scale (FOIS). Design Longitudinal cohort study. Setting Three secondary-level hospitals. Participants Invasively ventilated patients (N=28) who were hospitalized with severe COVID-19 and referred to the hospitals’ speech and language pathology (SLP) departments after mechanical ventilation between March 5 and July 5, 2020 for an evaluation of swallowing function before commencing oral diet. Interventions SLP assessment, advice, and therapy for dysphagia. Main Outcome Measures Oral intake levels at baseline and hospital discharge according to the FOIS. Patients were stratified according to FOIS (1-5, dysphagia; 6-7, functional oral intake). Data regarding comorbidities, frailty, intubation and tracheostomy, proning, and SLP evaluation were collected. Results Dysphagia was found in 71% of the patients at baseline (79% men; age, 61±12y; body mass index, 30±8 kg/m2). The median FOIS score at baseline was 2 (interquartile range [IQR], 1) vs 5 (IQR, 2.5) at hospital discharge. Patients with dysphagia were older (64±8.5y vs 53±16y; P=.019), had a higher incidence of hypertension (70% vs 12%; P=.006), and were ventilated invasively longer (16±7d vs 10±2d; P=.017) or had a tracheostomy (9±9d vs 1±2d; P=.03) longer. A negative association was found between swallowing dysfunction at bedside and days hospitalized (r=–0.471, P=.01), and number of days in the intensive care unit (ICU) (r=–0.48, P=.01). Conclusion Dysphagia is prevalent in COVID-19 patients after invasive mechanical ventilation and is associated with number of days in hospital and number of days in the ICU. Swallowing function and tolerance of oral diet improved at discharge (P&lt;.001)

Clinical frailty scale as a predictor of disease severity in patients hospitalised with COVID-19 -an observational cohort study

Background: The coronavirus disease 2019 pandemic makes proper resource allocation and prioritisation important. Frailty increases the risk of adverse outcomes and can be quantified using the Clinical frailty scale. The aim of this study was to determine the role of the Clinical frailty scale, in patients &gt;= 65 years of age with coronavirus disease 2019, as a risk factor either for critical coronavirus disease 2019 measured as intensive care unit admission or death or as a risk factor for death. Methods: This was a retrospective observational study on patients &gt;= 65 years hospitalised with coronavirus disease 2019 verified by polymerase chain reaction between 5 March 5 and 5 July 2020. The association between Clinical frailty scale and the composite primary outcome intensive care unit admission or death within 30 days post hospitalisation and the secondary outcome death within 30 days post hospitalisation was analysed using multivariable logistic regression models adjusting for gender, age, body mass index, hypertension, and diabetes. Clinical frailty scale was used as a categorical variable (fit score 1-4, frail score 5-6, and severely frail score 7-9). Results: In total, 169 patients were included (47.3% women, mean age 79.2 +/- 7.8 years). In the fully adjusted model, adjusted odds ratio for intensive care unit admission or death was 1.84 (95%-confidence interval 0.67-5.03, p = .234) for frail and 6.08 (1.70-21.81, p = .006) for severely frail compared to fit patients. For death, adjusted odds ratio was 2.81 (0.89-8.88, p = .079) for frail and 9.82 (2.53-38.10, p = .001) for severely frail compared to fit patients. Conclusions: A high Clinical frailty scale score was an independent risk factor for the composite outcome intensive care unit admission or death and for the secondary outcome death

Plasma Proteomic Analysis in Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Blockade

Simple Summary Immunotherapy leads to highly variable responses in lung cancer patients. We assessed the value of a blood-based test to predict which patients would benefit from this new treatment modality. We determined that some patients have higher and lower levels of immune markers in their blood samples, and that this is related to better survival without tumor growth. The blood test has the potential to help select the optimal therapy for lung cancer patients. Checkpoint inhibitors have been approved for the treatment of non-small cell lung cancer (NSCLC). However, only a minority of patients demonstrate a durable clinical response. PD-L1 scoring is currently the only biomarker measure routinely used to select patients for immunotherapy, but its predictive accuracy is modest. The aim of our study was to evaluate a proteomic assay for the analysis of patient plasma in the context of immunotherapy. Pretreatment plasma samples from 43 NSCLC patients who received anti-PD-(L)1 therapy were analyzed using a proximity extension assay (PEA) to quantify 92 different immune oncology-related proteins. The plasma protein levels were associated with clinical and histopathological parameters, as well as therapy response and survival. Unsupervised hierarchical cluster analysis revealed two patient groups with distinct protein profiles associated with high and low immune protein levels, designated as "hot" and "cold". Further supervised cluster analysis based on T-cell activation markers showed that higher levels of T-cell activation markers were associated with longer progression-free survival (PFS) (p &lt; 0.01). The analysis of single proteins revealed that high plasma levels of CXCL9 and CXCL10 and low ADA levels were associated with better response and prolonged PFS (p &lt; 0.05). Moreover, in an explorative response prediction model, the combination of protein markers (CXCL9, CXCL10, IL-15, CASP8, and ADA) resulted in higher accuracy in predicting response than tumor PD-L1 expression or each protein assayed individually. Our findings demonstrate a proof of concept for the use of multiplex plasma protein levels as a tool for anti-PD-(L)1 response prediction in NSCLC. Additionally, we identified protein signatures that could predict the response to anti-PD-(L)1 therapy

Mucin staining is of limited value in addition to basic immunohistochemical analyses in the diagnostics of non-small cell lung cancer

Accurate diagnosis of histological type is important for therapy selection in lung cancer. Immunohistochemical (IHC) and histochemical stains are often used to complement morphology for definite diagnosis and are incorporated in the WHO classification. Our main aim was to compare different mucin stains and assess their value in relation to common IHC analyses in lung cancer diagnostics. Using tissue microarrays from 657 surgically treated primary lung cancers, we evaluated the mucin stains periodic acid-Schiff with diastase (PASD), alcian blue-periodic acid-Schiff (ABPAS) and mucicarmine, and compared with the IHC markers p40, p63, cytokeratin 5, thyroid transcription factor 1 (TTF-1), napsin A and cytokeratin 7. Ten or more cytoplasmic mucin inclusions in a tissue microarray core were seen in 51%, 48% and 31% of the 416 adenocarcinomas and 3%, 4% and 0.5% of the 194 squamous cell carcinomas with PASD, ABPAS and mucicarmine, respectively. Diagnostic pitfalls, such as entrapped benign epithelium, apoptotic/necrotic cells and glycogen, partly differed for the mucin stains. TTF-1 and napsin A IHC stainings had similar specificity but better sensitivity for adenocarcinoma than the mucin stains, but addition of PASD or ABPAS identified more tumors as adenocarcinomas (n = 8 and n = 10, respectively) than napsin A (n = 1) in cases with solid growth that were negative for TTF-1 and p40. We conclude that PASD and ABPAS have similar diagnostic performance and that these markers are of value in poorly differentiated cases. However, morphology and TTF-1 and p40 IHC staining is sufficient for correct diagnosis in most non-small cell lung cancers