Wpływ zmiany wytycznych ASCO-CAP na ocenę statusu genu HER2 metodą FISH w kwalifikacji do terapii anty-HER2 w raku piersi

Introduction. Breast cancer is the most common cancer among Polish women. Overexpression of the HER2 protein or HER2 gene amplification is associated with a poor prognosis, simultaneously being an indication for the HER2-targeted therapy. In equivocal cases, the FISH assay is used for the final identification of the HER2 gene status. This evaluation should be performed according to the ASCO-CAP guidelines which have been changed in 2013. The aim of this study was to assess whether and how the changes of recommendations affected the distribution of the FISH results. Materials and methods. The results of routine diagnostic FISH analyses were compared for two independent groups of patients assessed with different evaluation criteria (ASCO-CAP 2007 for n = 680 and ASCO-CAP 2013 n = 851), and also in a group of 763 patients, where both criteria were used simultaneously. Results. A comparison of the results obtained in two independent groups showed that the change of evaluation criteria did not alter the percentage of HER2-positive tests (with HER2 amplification). However, the frequency of HER2-negative analyses (without HER2 amplification) diminished significantly from 76.2% to 61.8%, whereas the equivocal group (with an indefinite status of HER2 amplification) increased from 0.4% to 13.6%. In the group where both criteria from 2007 and 2013 were used, we also discovered statistically significant differences. The frequency of HER2-positive results were elevated from 10.6% to 16.8%. The equivocal results were also found more often, rising from 4.2% to 15.6%, while the number of negative results lowered from 85.2% to 67.6%. Conclusions. The use of ASCO/CAP recommendations for the assessment of the HER2 gene status reduces the group of negative results, and concurrently enlarges the number of positive and equivocal ones. This indicates that the new criteria extends the access to HER2-targeted therapy. Nevertheless, they also raise the frequency of analyses with an indefinite status of the HER2 gene. Our outcome suggests that there is a need for an enhanced FISH-based evaluation of this gene in the last group of patients in order to provide them with an unambiguous stratification to risk groups.  Wstęp. Rak piersi jest najczęstszym nowotworem u kobiet w Polsce. Nadmierna ekspresja białka HER2 lub amplifikacja genu HER2 jest związana ze złym rokowaniem i stanowi wskazanie do zastosowania terapii anty-HER2. W przypadkach wątpliwych rozstrzygającym badaniem jest ocena FISH, wskazująca status amplifikacji genu HER2 według obowiązujących wytycznych ASCO-CAP, które w roku 2013 uległy zmianom. Celem pracy było sprawdzenie, czy i w jaki sposób zmiana zaleceń wpłynęła na rozkład wyników badań FISH w tej grupie pacjentów. Materiały i metody. Analizie porównawczej poddano wyniki rutynowej diagnostyki metodą FISH w dwóch niezależnych grupach pacjentów z zastosowaniem dwóch różnych kryteriów oceny (ASCO-CAP 2007 dla n = 680 i ASCO-CAP 2013 dla n = 851) oraz w grupie 763 pacjentów, gdzie zastosowano równolegle obydwa kryteria oceny. Wyniki. Porównanie wyników uzyskanych w dwóch niezależnych grupach wykazało brak istotnej zmiany odsetka wyników HER2-dodatnich (z amplifikacją) po zmianie kryteriów oceny. Istotne statystycznie okazało się zmniejszenie grupy wyników HER2-negatywnych (bez amplifikacji) z 76,2% na 61,8% przy rozszerzeniu grupy niejednoznacznej (o nieokreślonym statusie amplifikacji) z 0,4% do 13,6%. Grupa badana równolegle wg kryteriów 2007 i 2013 wykazała różnice istotne statystycznie. Zanotowano wzrost przypadków HER2-pozytywnych z 10,6% do 16,8%, znaczny wzrost wyników niejednoznacznych, z 4,2% na 15,6%, przy równoczesnym spadku wyników negatywnych z 85,2% na 67,6%. Wnioski. Zastosowanie nowych wytycznych ASCO-CAP 2013 w ocenie statusu genu HER2 wpływa na zawężenie grupy wyników negatywnych, natomiast rozszerza grupę wyników pozytywnych i niejednoznacznych. Wynik taki wskazuje na rozszerzenie dostępu do kwalifikacji w kierunku terapii anty-HER2. Natomiast istotny wzrost odsetka pacjentów z wynikiem o nieokreślonym statusie amplifikacji genu HER2 wskazuje na konieczność pogłębionej w tej grupie oceny FISH w celu uzyskania możliwości jednoznacznej stratyfikacji do grup ryzyka.

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

The impact of the nutritional state of patients on the results of the surgical treatment of crohn’s disease

Crohn’s disease (CD) patients are qualified for surgery in the acute phase of the disease or after ineffective medical therapy. The course of the disease and the medical treatment received to that point weaken the general state of patients, with that they also cause undernutrition. The aim of the study was the assessment of the nutritional state of 168 CD patients, admitted for surgery and the evaluation of the influence of this state on the postoperative course. Material and methods. We referred the results of the nutritional state assessment to the time of the postoperative hospitalization of patients. Results. Applying the Kruskal-Wallis test we found statistically significant, but weakly expressed, differences between the values of nutritional state parameters and period of hospitalization of patients. The applied U Mann-Whitney test, with statistically significant results with p <0.05, showed that no one parameter of the nutritional state of patients expressed a statistically significant difference between dead and recovered groups. Conclusions. We propose the body mass loss in the 6 months period before admission, TLC and serum albumin level as parameters which well detect undernutrition in CD patients presenting for surger

The Impact of the Nutritional State of Patients on the Results of the Surgical Treatment of Ulcerative Colitis

A variety of mechanisms have been proposed to explain the malnutrition and body mass loss in UC patients. The aim of the study trial was a nutritional state assessment of 347 UC patients, admitted for surgical treatment, and the evaluation of the impact of this state on the postoperative course in this group of patients. Material and methods. We referred the results of nutritional state assessment to the length of time of postoperative hospitalization of patients. Results. Through application of the Kruskal-Wallis test we found statistically significant, but weakly expressed, differences between the values of nutritional state parameters and period of hospitalization of patients. The applied U Mann-Whitney test, with statistically significant results with p <0.05, showed statistically significant differences between cured and dead subgroups in: 1) loss of body mass in 6 months before hospitalization (p = 0.000033), 2) hemoglobin level (p = 0.006676), 3) total lymphocyte count (TLC) (p = 0.025242), 4) total serum protein level (p = 0.003485), 5) serum albumin level (p =0.00165). Differences in BMI values were statistically negligible (p = 0.969397). Conclusions. The body mass loss in 6 months before admission, total lymphocyte count and serum albumin level are the reference parameters of the nutritional state of UC patients on admission to surger

The association between paracetamol use and the risk of asthma, rhinitis and eczema in the Polish population

Introduction A growing number of epidemiological studies suggest that paracetamol, which is commonly used in children, may be a risk factor for asthma, allergic rhinitis, and atopic eczema. Objective The aim of this study was to determine and characterize the correlation between paracetamol use and asthma, allergic rhinitis, and atopic eczema symptoms in the Polish population. Material and methods The study is part of the ECAP project involving the use of the ISAAC and ECRHS questionnaires. Completed questionnaires of 18,617 subjects, including 10,011 (53.8%) females, were analyzed. Children aged 6–7 (n=4,510), adolescents aged 13–14 (n=4,721), and adults aged 20–44 (n=9,386) constituted 24.2%, 25.4%, and 50.4% of respondents, respectively. Study subjects lived in 8 major urban centres and one rural area. The frequency of paracetamol use during the previous 12 months and symptoms of asthma, allergic rhinitis, and atopic eczema during that period were analyzed. Results The use of paracetamol was associated with a significant dose-dependent increase in the risk of asthma symptoms in all evaluated age groups. This was demonstrated via odds ratios (OR) for developing asthma symptoms, including wheezing or whistling in the chest in 6–7-year-olds and exercise-induced shortness of breath in 13–14-year-olds and adults, depending on the frequency of paracetamol use in the previous 12 months, compared to no paracetamol intake during that period. Conclusions The use of paracetamol in the last 12 months was associated with a significant dose-dependent increase in the risk of rhinitis and skin allergy symptoms, as demonstrated by the odds ratio. Therefore, frequent paracetamol use may be a risk factor for symptoms of asthma, rhinitis, and skin allergy in the Polish population