Prognostic Significance of Tumor-associated Stroma in Nasopharyngeal Carcinoma: A Multicenter Study.

Assessment of tumor-associated stroma has shown a reliable prognostic value in recent research. We evaluated the prognostic value of tumor-stroma ratio (TSR) in a large multicenter cohort of nasopharyngeal carcinoma (NPC). We used the conventional hematoxylin and eosin-stained slides of 115 cases of NPC to assess TSR as described in recent guidelines. The amount of tumor-associated stroma was assessed as a percentage and then tumors were classified as stroma-high (>50%) or stroma-low (≤50%). Kaplan-Meier curves, χ 2 test, and Cox regression univariable and multivariable analyses were carried out. A total of 48 (41.7%) tumors were stroma-high and 67 (58.3%) tumors were stroma-low. In the Cox regression multivariable analysis, the tumors categorized as stroma-high were associated with a worse overall survival with a hazard ratio of 2.30 (95% CI: 1.27-4.15, P =0.006) and with poor disease-specific survival (hazard ratio=1.87, 95% CI: 1.07-3.28, P =0.029). The assessment of TSR in NPC is simple and cost-effective, and it has a significant prognostic value. TSR can aid in risk stratification and clinical decision-making in NPC.

Perceptions of professional social media interaction with patients and faculty members - a comparative survey among dental students from Malaysia and Finland.

BACKGROUND: Professional and personal boundaries are blurred with the wide application of social media (SM) in the health professions line of work. Little is known about practice of extending friend requests to patients and faculty members among dental students, which encompass a part of E-professionalism. The aim of this study is to assess the factors associated with the perceptions and practices of interactions with patients and faculty on SM among dental students from Malaysia and Finland. METHODS: Dental students from 4 institutions in Malaysia and Finland completed self-administered questionnaires on the practices and perceptions of SM use. The main variables assessed were the perceptions and practices of student-patient and student-faculty communication on SM, between the two countries. Students' country, age, gender, time spent on SM and perceived importance of communicating dental related aspects over SM were analysed as potential explanatory variables. Crosstabulation was used to estimate the distributions of the response variables by the background characteristics. Multivariate analyses were performed using a dichotomous logistic regression model to investigate relevant associations between the responses and the explanatory variables independent from other factors. RESULTS: A total of 643 students completed the survey in March-April 2021. More Malaysian students agreed with "guiding patients online is a new responsibility for dentists in the digital age" compared to Finnish students (86.4% vs. 73.4%). Similarly, significantly more Malaysian students befriended patients (14.1% vs. 1%) and invited faculty to be friends on SM (73.6% vs. 11.8%). Expectedly, clinical year students befriended patients more than pre-clinical (13.8% vs. 6.8%). Significantly more students who felt 'communication of dental related issues over SM' were likely to extend friend requests to faculty rather than accept patient friend requests. CONCLUSIONS: Social media regulations and socio-cultural practices contribute to dental students' attitudes and behaviour when befriending patients and faculty members on social media. Future dental curriculum should incorporate guidelines for professional communication on social media based on local and cultural needs. Students' should be encouraged to interact with their patients using professional identities on social media.

Association Between Blood Eosinophils and Neutrophils With Clinical Features in Adult-Onset Asthma.

BACKGROUND: Asthma is a disease that can be separated into different phenotypes and endotypes based on the clinical characteristics and the molecular mechanisms of the condition, respectively. OBJECTIVE: To assess the association between blood eosinophil and neutrophil counts with clinical and molecular features in patients with adult-onset asthma. METHODS: Blood eosinophil and neutrophil counts were measured from 203 patients who took part in the Seinäjoki Adult Asthma Study and attended the 12-year follow-up visit. The patients were then divided into four groups (paucigranulocytic [n = 108], neutrophilic [n = 60], eosinophilic [n = 21], and mixed granulocytic [n = 14]), according to eosinophil and neutrophil levels. The cutoff values used to define the groups were 0.30 × 109 · L-1 for blood eosinophils and 4.4 × 109 · L-1 for blood neutrophils. RESULTS: The neutrophilic group had highest body mass index. It was dispensed the highest doses of inhaled corticosteroids during the 12-year follow-up and made the most unplanned respiratory visits. The neutrophilic, eosinophilic, and mixed granulocytic groups had more severe asthma compared with the paucigranulocytic group. The neutrophilic and eosinophilic groups were associated with higher dispensed antibiotics. The eosinophilic group had more nasal polyps, more suspected sinusitis, a greater decline in lung function, and increased levels of periostin, FeNO, and IgE. The neutrophilic group had increased high-sensitivity C-reactive protein, matrix metalloproteinase-9, IL-6, leptin, and soluble urokinase plasminogen activator receptor levels. The mixed granulocytic group showed increased resistin levels together with the neutrophilic group. CONCLUSIONS: In addition to blood eosinophils, the blood neutrophil count reflects underlying inflammatory patterns and indicates important differences in asthma clinical features and outcomes.

Tertiary lymphoid structures associate with improved survival in early oral tongue cancer.

BACKGROUND: The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC). METHODS: A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area. RESULTS: The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan-Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09-3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11-2.48; P = 0.014). CONCLUSION: Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system.

Research on Selected Wildlife Infections in the Circumpolar Arctic-A Bibliometric Review.

One Health, a multidisciplinary approach to public health, which integrates human, animal, and environmental studies, is prudent for circumpolar Arctic health research. The objective of our bibliometric review was to identify and compare research in select infectious diseases in Arctic wildlife species with importance to human health indexed in English language databases (PubMed, Scopus) and the Russian database eLibrary.ru. Included articles (in English and Russian languages) needed to meet the following criteria: (1) data comes from the Arctic, (2) articles report original research or surveillance reports, (3) articles were published between 1990 and 2018, and (4) research relates to naturally occurring infections. Of the included articles (total n = 352), most were from Russia (n = 131, 37%), Norway (n = 58, 16%), Canada (n = 39, 11%), and Alaska (n = 39, 11%). Frequently reported infectious agents among selected mammals were Trichinella spp. (n = 39), Brucella spp. (n = 25), rabies virus (n = 11), Echinococcus spp. (n = 10), and Francisella tularensis (n = 9). There were 25 articles on anthrax in eLibrary.ru, while there were none in the other two databases. We identified future directions where opportunities for further research, collaboration, systematic reviews, or monitoring programs are possible and needed.

Putative anoikis resistant subpopulations are enriched in lymph node metastases and indicate adverse prognosis in colorectal carcinoma.

Anoikis refers to apoptosis induced by the loss of contact with the extracellular matrix. Anoikis resistance is essential for metastasis. We have recently shown that it is possible to quantitatively evaluate putative anoikis resistant (AR) subpopulations in colorectal carcinoma (CRC). Abundance of these multi-cell structures is an independent marker of adverse prognosis. Here, we have quantified putative AR subpopulations in lymph node (LN) metastases of CRC and evaluated their prognostic value and relationship with the characteristics of primary tumors. A case series included 137 unselected CRC patients, 54 with LN metastases. Areal densities (structures/mm2) of putative AR structures in primary tumors had been analyzed previously and now were determined from all nodal metastases (n = 183). Areal density of putative AR structures was higher in LN metastases than in primary tumors. Variation of the areal density within different LN metastases of a single patient was lower than between metastases of different patients. Abundance of putative AR structures in LN metastases was associated with shorter cancer specific survival (p = 0.013), and this association was independent of T and N stages. Abundance of putative AR structures in primary tumors and LN metastases had a cumulative adverse effect on prognosis. Enrichment of putative AR subpopulations in LN metastases suggest that in metastasis formation, there is a selection favoring cells capable of forming these structures. Higher intra-case constancy relative to inter-case variation suggests that such selection is stable in metastasis development. Our findings indirectly support the biological validity of our concept of putative AR structures.

E-Professionalism among Dental Students from Malaysia and Finland.

The increased use of social media in dentistry is associated with both advantages and disadvantages. A new form of professionalism, "e-professionalism," has emerged. It includes an online persona and online information in any format that displays cues to professional identity, attitudes, and behaviors. The objective was to explore the perceptions of Malaysian and Finnish dental students on e-professionalism. A survey of 613 Malaysian and Finnish students was performed. The main variables assessed were posting of objectionable or inappropriate content among students, attitudes towards unprofessional online content, perceived online presence, contacts with patients and faculty members on social media, and concerns about social media use. The prevalence of posting clearly unprofessional content was not high among dental students. Revealing information of patients was most common content of clear unprofessionalism. Students from Malaysia contacted patients and faculty members more actively in social media than students in Finland (73.6% of students in Malaysia and 11.8% in Finland had invited faculty members to be "friends"). Malaysian students were more concerned and more likely to react to inappropriate content on social media. Attitude of dental students towards social media use in dentistry were very positive in both countries. Students agreed that guiding patients online is a new responsibility for dentists in the digital age (86.4% of students in Malaysia and 73.4% in Finland). The findings indicate the existence of both benefits and dangers of social media on e-professionalism among students. There is a need to include robust digital professionalism awareness training for students.

Job demands and job control among occupational therapists in public sector in Finland.

BACKGROUND: Although health care professionals' increased job demands and strain have generated much public debate in recent years, the way in which occupational therapists' job strain has developed remains unknown. OBJECTIVE: To examine how Finnish occupational therapists working in municipalities experienced job demands and control in 2014-2018 compared with physiotherapists and registered nurses. MATERIAL AND METHODS: Occupational therapists (OT, n = 107), physiotherapists (PT, n = 331) and registered nurses (RN, n = 1389) responded to repeated surveys in the Finnish Public Sector Study in 2014-2018. We used the Job Content Questionnaire and analyzed the data using repeated measures analysis of variance and multiple linear regression with generalized estimating equations to identify the trends and differences. RESULTS: More OTs had lower job demands and higher job control than PTs and RNs in each year of study. These differences were statistically significant. Most OTs had low job strain. The changes in job control and job demands of participants in different years were not statistically significant. CONCLUSIONS: The OTs consistently experienced low job strain as compared to the PTs and RNs. Developing good practices in OT's work may be beneficial for improving employee health and well-being and high-quality client care.

Social Media Usage among Dental Undergraduate Students-A Comparative Study.

Social media use among students has infiltrated into dental education and offers benefits but may also cause problems. The aim of this study was to explore and compare current social media usage among dental undergraduate students from two countries-Malaysia and Finland. A self-administered structured online questionnaire was used. WhatsApp, YouTube, Instagram, Facebook and Snapchat were the services that were most familiar to the respondents from both countries. There were differences between the students from the two countries among the most preferred platforms. The most frequently used applications were WhatsApp (91.1% of students in Malaysia and 96.1% in Finland used it very frequently) and Instagram (74.3% of students in Malaysia and 70.0% in Finland used it very frequently). Students in Malaysia spent significantly more hours per week using the platforms as study tools than students in Finland. Over 80% of the Finnish dental students reported that lack of knowledge was not an issue in social media usage, while 85% of Malaysian students felt that lack of knowledge prevented them from using social media platforms frequently. The findings offer evidence that dental students used social media extensively.

The Quality of Statistical Reporting and Data Presentation in Predatory Dental Journals Was Lower Than in Non-Predatory Journals.

Proper peer review and quality of published articles are often regarded as signs of reliable scientific journals. The aim of this study was to compare whether the quality of statistical reporting and data presentation differs among articles published in 'predatory dental journals' and in other dental journals. We evaluated 50 articles published in 'predatory open access (OA) journals' and 100 clinical trials published in legitimate dental journals between 2019 and 2020. The quality of statistical reporting and data presentation of each paper was assessed on a scale from 0 (poor) to 10 (high). The mean (SD) quality score of the statistical reporting and data presentation was 2.5 (1.4) for the predatory OA journals, 4.8 (1.8) for the legitimate OA journals, and 5.6 (1.8) for the more visible dental journals. The mean values differed significantly (p < 0.001). The quality of statistical reporting of clinical studies published in predatory journals was found to be lower than in open access and highly cited journals. This difference in quality is a wake-up call to consume study results critically. Poor statistical reporting indicates wider general lower quality in publications where the authors and journals are less likely to be critiqued by peer review.

FAK, paxillin, and PI3K in ameloblastoma and adenomatoid odontogenic tumor.

OBJECTIVE: Integrins function to bind cells to extracellular matrix in tissues, which triggers downstream signaling cascades that are important in cell survival, proliferation, cytokine activation, and cytoskeleton reorganization. These processes also play significant roles in neoplasms. This work aimed to investigate the pattern of expression of FAK, paxillin, and PI3K in ameloblastoma and adenomatoid odontogenic tumor (AOT). MATERIALS AND METHODS: Immunohistochemistry was used to study FAK, paxillin, and PI3K in 45 ameloblastomas (32 conventional, 12 unicystic, and 1 peripheral types), 7 AOTs, and two developing human teeth. RESULTS: Weak expression of FAK was seen in all AOT cases, while ameloblastoma had varying expression patterns, mostly strong to weak. The pattern of expression of paxillin and PI3K was relatively similar in both tumor types. In the dental germ, FAK and paxillin stained all the enamel organ components, while PI3K stained strongly the inner enamel epithelium. Stromal expression of FAK was not found to be useful in differentiating between tumors or tumor classes. CONCLUSION: The expression of the proteins in the enamel organ suggests that their signaling may be important in odontogenesis. While some ameloblastomas strongly expressed FAK, all cases of AOT had weak signals suggesting low presence and phosphorylating activity of FAK in the latter. CLINICAL RELEVANCE: A subset of FAK-positive ameloblastoma (as well as their malignant or metastasizing counterparts) which may have relatively aggressive behavior may be candidates for drug targeting of FAK as an additional management option.

Long-term prognosis of new adult-onset asthma in obese patients.

BACKGROUND: Obesity has been associated with poor outcomes of asthma in cross-sectional studies, but long-term effect of obesity on asthma remains unknown. AIMS: To study the effects of obesity, found at the time of diagnosis of adult-onset asthma, on 12-year prognosis by focusing on oral corticosteroid (OCS) use and respiratory-related hospital admissions. METHODS: Patients diagnosed with adult-onset asthma (n=203) were divided into three categories based on diagnostic body mass index (BMI) (<25 kg·m-2, 25-29.9 kg·m-2, ≥30 kg·m-2) and followed for 12 years as part of the Seinäjoki Adult Asthma Study. Self-reported and dispensed OCS were assessed for the 12-year period. Data on hospital admissions were analysed based on medical records. RESULTS: 12 years after diagnosis, 86% of the patients who were obese (BMI ≥30 kg·m-2) at diagnosis remained obese. During the follow-up, no difference was found in weight gain between the BMI categories. During the 12-year follow-up, patients obese at diagnosis reported more frequent use of OCS courses (46.9% versus 23.1%, p=0.028), were dispensed OCS more often (81.6% versus 56.9%, p=0.014) and at higher doses (median 1350 (interquartile range 280-3180) mg versus 600 (0-1650) mg prednisolone, p=0.010) compared to normal-weight patients. Furthermore, patients who were obese had more often one or more respiratory-related hospitalisations compared to normal-weight patients (38.8% versus 16.9%, p=0.033). In multivariate logistic regression analyses, obesity predicted OCS use and hospital admissions. CONCLUSIONS: In adult-onset asthma, patients obese at diagnosis mostly remained obese at long-term and had more exacerbations and respiratory-related hospital admissions compared to normal-weight patients during 12-year follow-up. Weight loss should be a priority in their treatment to prevent this outcome.

Biopsy quality is essential for preoperative prognostication in oral tongue cancer.

A role for incisional biopsy in preoperative prognostication is increasingly being advocated in oral tongue squamous cell carcinomas (OTSCC). Biopsies at two locations were compared, and prognostic factors in biopsies and their corresponding resections were evaluated. A total of 138 OTSCC biopsy slides from Finland and Saudi Arabia were compared for size (horizontal and vertical) and invasive front. The Finnish cases were assessed for tumor stroma ratio (TSR) and tumor-infiltrating lymphocytes (TILs) using light microscopy and digital image analysis assessment and compared. Furthermore, TSR, TILs, and previously analyzed budding and depth of invasion (BD) score in biopsies were compared with their evaluation in the corresponding resections. Fifty-nine percent of Finnish and 42% of Saudi Arabian biopsies were ≥ 5 mm deep, while 98% of Saudi Arabian and 76% of Finnish biopsies were ≥ 5 mm wide. Assessment of invasion front was possible in 72% of Finnish in comparison with 40% of Saudi Arabian biopsies. There was 86.8% agreement between TSR and 75% agreement between TIL evaluation using light microscopy and digital assessment. Significant agreement was obtained on comparing the TSR (p = 0.04) and BD (p < 0.001) values in biopsies and resections. Biopsies of ≥ 5 mm depth from representative OTSCC areas are essential for prognostic information. Clinical pathologists are advised to assess BD score and TSR for prognostic features in such biopsies.

Stromal categorization in early oral tongue cancer.

Stromal categorization has been used to classify many epithelial cancer types. We assessed the desmoplastic reaction and compared its significance with other stromal characteristics in early (cT1-2N0) oral tongue squamous cell carcinoma (OTSCC). In this multi-institutional study, we included 308 cases treated for early OTSCC at five Finnish university hospitals or at the A.C. Camargo Cancer Center in São Paulo, Brazil. The desmoplastic reaction was classified as immature, intermediate, or mature based on the amount of hyalinized keloid-like collagen and myxoid stroma. We compared the prognostic value of the desmoplastic reaction with a stromal grading system based on tumor-stroma ratio and stromal tumor-infiltrating lymphocytes. We found that a high amount of stroma with a weak infiltration of lymphocytes was associated statistically significantly with a worse disease-free survival with a hazard ratio (HR) of 2.68 (95% CI 1.26-5.69), worse overall survival (HR 2.95, 95% CI 1.69-5.15), and poor disease-specific survival (HR 2.66, 95% CI 1.11-6.33). Tumors having a high amount of stroma with a weak infiltration of lymphocytes were also significantly associated with a high rate of local recurrence (HR 4.13, 95% CI 1.67-10.24), but no significant association was found with lymph node metastasis (HR 1.27, 95% CI 0.37-4.35). Categorization of the stroma based on desmoplastic reaction (immature, intermediate, mature) showed a low prognostic value for early OTSCC in all survival analyses (P > 0.05). In conclusion, categorization of the stroma based on the amount of stroma and its infiltrating lymphocytes shows clinical relevance in early OTSCC superior to categorization based on the maturity of stroma.

Cell-in-cell phenomenon associates with aggressive characteristics and cancer-related mortality in early oral tongue cancer.

BACKGROUND: Cell-in-cell structures (caused by cell cannibalistic activity) have been related to prognosis of many cancers. This is the first multi-institutional study to assess the prognostic impact of cell-in-cell structures in a large cohort of early oral tongue squamous cell carcinomas (OTSCC). METHODS: A total of 308 cases from five Finnish University Hospitals and from the A.C. Camargo Cancer Center, São Paulo, Brazil, were included in this study. Cell-in-cell structures were evaluated on surgical postoperative sections that stained with hematoxylin and eosin staining. RESULTS: We found that cell-in-cell structures associated with cancer-related mortality in univariable analysis with a hazard ratio (HR) of 2.99 (95%CI 1.52-5.88; P = 0.001). This association was confirmed in multivariable analysis (HR 2.22, 95%CI 1.12-4.44; P = 0.024). In addition, statistically significant associations were observed between the cell-in-cell structures and other adverse histopathologic characteristics including deep invasion (P <  0.001), high index of tumor budding (P = 0.007), worst pattern of invasion (P <  0.001), perineural invasion (P = 0.01), and stroma-rich pattern (P = 0.001). CONCLUSIONS: Our findings demonstrate a significant relationship between cell-in-cell formation and aggressive characteristics of early OTSCC. Cell-in-cell structures have a distinct impact as a novel prognostic indicator in early OTSCC and they can be easily assessed during routine pathology practice.

Information Retrieval and Awareness about Evidence-Based Dentistry among Dental Undergraduate Students-A Comparative Study between Students from Malaysia and Finland.

BACKGROUND: A fundamental skill in education includes the ability to search for, evaluate, and synthesize information, and this cannot be underestimated in dental education. The aim of this study was to assess how dental students from Malaysia and Finland acquire scientific information and to compare their information retrieval skills. METHODS: Fourth and fifth-year dental students from Malaysia and Finland were invited to participate. A self-administered structured questionnaire including items about the use of information sources, subjective assessment of literature retrieval skills and knowledge was used. RESULTS: A total of 226 dental students participated in the survey: 131 from Malaysia and 95 from Finland. In both countries, the highest interest for data retrieval among students was found in the oral surgery specialty. The three most used sources of information among Malaysian students were personal lecture notes, dental textbooks, and colleagues; while Finnish students used colleagues, lecture notes, and current clinical guidelines. Students' knowledge of evidence-based practice was inadequate in both student groups. Though the majority of participants reported that they had good or passable skills in literature retrieval, more students from Finland judged themselves to have at least good skills compared to those from Malaysia. CONCLUSION: Dental education in both countries includes information retrieval studies and mandatory research projects. However, students did not often use those sources that are considered essential in evidence-based dentistry. Universities should further develop educational and training interventions that guide students to use knowledge resources more effectively for critically appraising scientific evidence.

Sputum Vitamin D Binding Protein (VDBP) GC1S/1S Genotype Predicts Airway Obstruction: A Prospective Study in Smokers with COPD.

Introduction: The vitamin D binding protein (VDBP, also known as GC-globulin) and vitamin D deficiency have been associated with chronic obstructive pulmonary disease (COPD). rs7041 and rs4588 are two single nucleotide polymorphisms of the VDBP gene, including three common allelic variants (GC1S, GC1F and GC2). Previous studies primarily assessed the serum levels of vitamin D and VDBP in COPD. However, less is known regarding the impact of the local release of VDBP on COPD lung function. Thus, we examined the association of sputum and plasma VDBP with lung function at baseline and at four years, and examined potential genetic polymorphism interactions. Methods: The baseline levels of sputum VDBP, plasma VDBP and plasma 25-OH vitamin D, as well as the GC rs4588 and rs7041 genotypes, were assessed in a 4-year Finnish follow-up cohort (n = 233) of non-smokers, and smokers with and without COPD. The associations between the VDBP levels and the longitudinal decline of lung function were further analysed. Results: High frequencies of the haplotypes in rs7041/rs4588 were homozygous GC1S/1S (42.5%). Higher sputum VDBP levels in stage I and stage II COPD were observed only in carriers with GC1S/1S genotype when compared with non-smokers (p = 0.034 and p = 0.002, respectively). Genotype multivariate regression analysis indicated that the baseline sputum VDBP and FEV1/FVC ratio at baseline independently predicted FEV1% at follow-up. Discussion and Conclusion: The baseline sputum VDBP expression was elevated in smokers with COPD among individuals with the GC1S/1S genotype, and predicted follow-up airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.

12-year adherence to inhaled corticosteroids in adult-onset asthma.

Adherence to inhaled corticosteroids (ICS) has been suggested to be poor but long-term follow-ups are lacking. The objective of the present study was to assess adherence to ICS treatment in patients with adult-onset asthma during 12-year follow-up. A total of 181 patients with clinically confirmed, new-onset adult asthma were followed for 12 years as part of the Seinäjoki Adult Asthma Study. Adherence to ICS was assessed individually as the percentage of true dispensed ICS in micrograms per true prescribed daily ICS in micrograms over 12 years. Mean 12-year adherence to ICS was 69% (mean±sd dispensed 2.5±1.8 g and prescribed 3.6±1.5 g budesonide equivalent per patient for 12 years), annual adherence varying between 81% (year 1) and 67% (year 12). Patients with good 12-year adherence (≥80%) used oral corticosteroids more often, and had add-on drugs in use and asthma-related visits to healthcare more often. In addition, they showed less reversibility in forced expiratory volume in 1 s and had higher peripheral blood neutrophil counts. However, lung function decline was steeper in patients with poorer adherence (<80%) and this association remained in multiple linear regression analysis. No difference was found in symptom scores, blood eosinophil counts, exhaled nitric oxide or immunoglobulin E between the patients with different levels of adherence. In patients with adult-onset asthma, adherence to ICS was moderate. Poorer adherence (<80%) to ICS was associated with more rapid decline in lung function but was not associated to symptoms or markers of inflammatory endotypes.

Putative anoikis-resistant subpopulations in colorectal carcinoma: a marker of adverse prognosis.

Anoikis is a form of apoptosis induced when a cell loses contact with the extracellular matrix (ECM). Anoikis resistance is essential for metastasis formation, yet only detectable by in vitro experiments. We present a method for quantitation of putative anoikis-resistant (AR) subpopulations in colorectal carcinoma (CRC) and evaluate their prognostic significance. We studied 137 CRC cases and identified cell subpopulations with and without stromal or extracellular matrix (ECM) contact with hematoxylin-and-eosin-stained sections and immunohistochemistry for laminin and type IV collagen. Suprabasal cells of micropapillary structures and inner cells of cribriform and solid structures lacked both stromal contact and contact with ECM proteins. Apoptosis rate (M30) was lower in these subpopulations than in the other carcinoma cells, consistent with putative AR subpopulation. We determined the areal density of these subpopulations (number/mm2 tumor tissue), and their high areal density independently indicates low cancer-specific survival. In conclusion, we show evidence that subpopulations of carcinoma cells in micropapillary, cribriform, and solid structures are resistant to anoikis as shown by lack of ECM contact and low apoptosis rate. Abundance of these subpopulations is a new independent indicator of poor prognosis in CRC, consistent with the importance of anoikis resistance in the formation of metastasis.