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Clinicopathological and Prognostic Analysis of Immunohistochemical PD-L1 and PD-L2 Expressions in Adult Acute Leukemias
No full textErişkinlerde en sık görülen akut lösemi Akut Myeloid Lösemi (AML) olup çocuklarda ise Akut Lenfoblastik Lösemi (ALL)’dir. Refrakter ve relaps (R/R) vakalar erişkin yaş grubunda daha sık görülmektedir. Son yıllarda malign tümör insidansının artması; kemoterapi, radyoterapinin immun sistemi zayıflatması ve bu tedavilerin ciddi yan etkilere neden olmasıyla immunoterapinin önemi artmıştır. Kanser immünoterapisinde immun checkpoint moleküllerinin keşfi ise büyük atılımlara yol açmış olup solid tümörlerin tedavilerinde ve hematolojik malignitelerde ise multiple myelomda kullanılmaya başlanmıştır. Çalışmamızda Necmettin Erbakan Üniversitesi Tıp Fakültesinde 2017-2023 yıllarında 18 yaş üzerinde tanı almış ve ek hastalığı (anti PD-1/anti PD-L1 tedavisi alan non hematolojik malignite, romatolojik ve otoimmun hastalıklar) olmayan 41 ALL ve 55 AML hastasının ilk tanı aldıkları kemik iliği biyopsisi bloklarından kesitler alınarak immunhistokimyasal PD-L1 ve PD-L2 boyamaları yapıldı. Blastik hücrelerdeki PD-L1 ve PD-L2 ekspresyonlarının boyanma yüzdeleri değerlendirildi ve sonuçlar klinikopatolojik ve genetik verilerle istatistiksel olarak kıyaslandı. PD-L1 ile cinsiyet arasında erkek cinsiyet lehine zayıf korelasyon (rho:0,266, p:0,009) ve ferritin ile de pozitif yönde korelasyon (p: 0,035) saptandı. PD-L2 ekspresyonu ile lösemi tipleri arasında AML (p:0,039) yönünde, yaş (p:0,003) ve selülarite (p:0,043) ile de pozitif yönde korelasyon izlendi. Sonuç olarak çalışmamızda PD-L1 pozitifliği ALL’de %43,9, AML’de %58,2; PD-L2 pozitifliği ise ALL’de %73,1, AML de %74,5 hastada tespit edilmesi nedeniyle tedavide anti PD-1 ve anti PD-L1 ajanlarının kullanımına yer verilebileceğini ayrıca PD-L1 ekspresyonu negatif saptanan hastaların 31 (%32,2)’inde PD-L2 ekspresyonu izlenmesi nedeniyle PD-L1 negatif olgularda dahi PD-L2 pozitifliği nedeniyle anti PD-1 ajanların kullanım yolunun açılabileceğini düşünmekteyiz. Çalışmamızda PD-L1 ve PD-L2 ekspresyonunun R/R vakalarda, toplam sağ kalım ile ilişkisinde, kötü risk gruplarının ortaya konmasında anlamlı farklılık saptanmamış olup daha geniş vaka serilerinde, flow sitometri veya FISH ile değerlendirildiğinde farklı sonuçların ortaya çıkabileceğini düşünmekteyiz.The most common acute leukemia in adults is Acute Myeloid Leukemia (AML), while in children it is Acute Lymphoblastic Leukemia (ALL). Refractory and relapsed (R/R) cases are more frequently observed in the adult age group. In recent years, the increasing incidence of malignant tumors, the immunosuppressive effects of chemotherapy and radiotherapy, and the serious side effects of these treatments have underscored the importance of immunotherapy. The discovery of immune checkpoint molecules in cancer immunotherapy has led to significant breakthroughs and has begun to be used in the treatment of solid tumors and hematologic malignancies, particularly in multiple myeloma.
In our study, immunohistochemical PD-L1 and PD-L2 staining were performed on sections obtained from bone marrow biopsy blocks of 41 ALL and 55 AML patients diagnosed at Necmettin Erbakan University Faculty of Medicine between 2017 and 2023, aged 18 and older, with no comorbidities (patients receiving anti-PD-1/anti-PD-L1 treatment for non-hematologic malignancies, rheumatologic, and autoimmune diseases). The percentages of PD-L1 and PD-L2 expression in blast cells were evaluated, and the results were statistically compared with clinicopathological and genetic data. A weak correlation was found between PD-L1 positivity and male gender (rho: 0.266, p: 0.009) and a positive correlation with ferritin (p: 0.035). PD-L2 expression showed a positive correlation with leukemia types towards AML (p: 0.039), age (p: 0.003), and cellularity (p: 0.043).
In conclusion, PD-L1 positivity was detected in 43.9% of ALL and 58.2% of AML patients in our study, while PD-L2 positivity was detected in 73.1% of ALL and 74.5% of AML patients. Therefore, we believe that anti-PD-1 and anti-PD-L1 agents can be incorporated into the treatment, and considering the presence of PD-L2 expression in 31 (32.2%) of patients with negative PD-L1 expression, we think that the use of anti-PD-1 agents may be considered even in cases where PD-L1 is negative due to the presence of PD-L2 positivity. In our study, no significant difference was found in the relationship between PD-L1 and PD-L2 expression in R/R cases and overall survival, or in identifying poor-risk groups. We think that different results may emerge when evaluated in larger case series, with flow cytometry or FISH
The relationship between nuclear properties and various prognostic factors in classical papillary thyroid carcinoma
Full text linkKlasik papiller tiroid karsinomlarının tanısında en önemli kriter olan nükleer özelliklerin çeşitli prognostik faktörlerle ilişkisinin araştırılması Yöntem: Bu tez çalışmasında Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi Patoloji Anabilim Dalı arşivinde bulunan Ocak 2018- Ocak 2019 yılları arasında tiroid papiller karsinomu tanısı almış ve total tiroidektomi ile klinik ve radyolojik olarak metastaz düşünülerek beraberinde lenf nodu diseksiyonu yapılmış olan olgular tespit edildi. Bu olgulardan parafin bloklarına ulaşılabilen uygun, klasik tip papiller tiroid karsinomu tanılı 30 olgu çalışma kapsamına alındı. Hastalara ait cinsiyet, yaş, tümör çapı, odak sayısı ve fokalite bilgileri arşivde bulunan patoloji raporlarından elde edildi. Çalışmada elde edilen veriler SPSS (Statistical Package for Social Sciences) 22.0 programı kullanılarak analiz edildi. Bulgular: Hastaların yaşı, tümör çapı ve tümör odak sayısı ile mitoz ve intranükleer sitoplazmik psödoinklüzyon sayımı, hücre nüvelerinde berraklaşma ve kalabalıklaşma oranlarının sayısal verileri arasında istatistiksel anlamlı bir korelasyon bulunmadı. Ekstratiroidal yayılım olan ve olmayan olgularda nüvelerde berraklaşma, kalabalıklaşma oranları, mitoz sayımı karşılaştırıldığında istatistiksel olarak anlamlı bir farklılık bulunamadı. Ekstratiroidal yayılım olan olgularda 50 BBA' da intranükleer psödoinklüzyon ortalama ve ortanca değeri daha yüksekti. Servikal lenf nodu metastazı olan ve olmayan olgularda nüvelerde berraklaşma, kalabalıklaşma oranları, mitoz ve intranükleer sitoplazmik psödoinklüzyon sayımı karşılaştırıldığında istatistiksel olarak anlamlı bir farklılık bulunamadı. Sonuç: Ekstratiroidal yayılım olan ve olmayan olgularda intranükleer psödoinklüzyon sayısı karşılaştırıldığında istatistiksel olarak anlamlı bir farklılık tespit edildi. Ekstratiroidal yayılım olan olgularda intranükleer psödoinklüzyon ortalama ve ortanca değeri daha yüksek bulundu. Anahtar Kelimeler: Klasik Papiller Tiroid Karsinomu, Nükleer Özellikler, Prognostik FaktörlerTo investigate the relationship between nuclear characteristics which the most important criteria in the diagnosis of classical type papillary thyroid carcinoma, and various prognostic factors. Method: In this thesis, thyroid papillary carcinoma diagnosed in the archives of Necmettin Erbakan University, Meram Medical Faculty Department of Medical Pathology between January 2018 and January 2019 was investigated. Thirty patients with conventional papillary thyroid carcinoma who could reach paraffin blocks were included in the study. Gender, age, tumor diameter, number of foci and focal information of the patients were obtained from the pathology reports in the archive. Data obtained from the study were analyzed using SPSS (Statistical Package for Social Sciences) 22.0 program. Results: No statistically significant correlation was found between the patients' age, tumor diameter and tumor focus number, and the numerical data of mitosis and intranuclear cytoplasmic pseudoinclusion count, cell nuclei clarity and crowding rates. No statistically significant difference was found between the clarification of the nuclei, crowding rates and mitosis count in cases with and without extrathyroid spread. The mean and median value of intranuclear pseudoinclusion in 50 HPF was higher in patients with extrathyroid spread. No statistically significant difference was found between nuclei clearance, crowding rates, mitosis and intranuclear cytoplasmic pseudoinclusion count in patients with and without cervical lymph node metastasis. Conclusion: When the number of intranuclear pseudoinclusion was compared in patients with and without extrathyroid spread, a statistically significant difference was found. The mean and median value of intranuclear pseudoinclusion was higher in patients with extrathyroid spread. Keywords: Classical Papillary Thyroid Carcinoma, Nuclear Features, Prognostic Factor
Comparative analysis of morphological and immunhistochemical (CD4 / CD8 T cell and CD123 (+) plasmacytoid dentritic cell ratios) of rosacea, discoid lupus erythematosus and polymorph light eruption lesions
Full text linkHistopatolojik olarak benzer bulgular içeren Polimorf Işık Erüpsiyonu (PIE), Diskoid Lupus Eritematozus ve Rozasea vakalarında histopatolojik analiz ile birlikte immünohistokimyasal olarak CD123 oranı ile plazmositoid dentritik hücre (PDH) varlığının ve lenfositlerdeki CD4/CD8 oranlarının karşılaştırılması, böylece doğru tanıya ulaşmada immünohistokimyanın katkısının araştırılması ve literatüre katkı sağlanmasını amaçladık. Yöntem: 2015-2020 yılları arasında Meram Tıp Fakültesi Patoloji Anabilim Dalı laboratuarında incelenerek tanı almış 27 adet DLE, 27 adet PIE ve 29 adet Rozasea olgusuna ait preparatlar histopatolojik olarak tekrar gözden geçirildi. Parafin bloklardan kesitler alınarak, immunohistokimyasal boyama cihazında CD4, CD8 ve CD123 boyamaları yapıldı, lezyonlardaki lenfositik infiltrasyonların CD4/CD8 oranları ve CD123 pozitif PDH oranları değerlendirildi. Sonuçlar hasta gruplarına göre listelenip istatistiksel olarak uyumluluk ve farklılıklar ortaya konuldu. Bulgular: İstatistiksel sonuçlarda histopatolojik bulgulardan olan folliküler plugging, Demodeks varlığı, ödem, spongioz, müsin birikimi, bazal membran kalınlaşması açısından vakalar arasında anlamlı fark tespit edildi (sırasıyla; p=0,003; p=<0,001; p=0,001; p=0,027; p=<0,001; p=<0,001). Demodeks varlığı Rozasea'da PIE ve DLE'ye göre, ödem ve spongioz PIE'de DLE'ye göre, folliküler plugging DLE ve Rozasea'da PIE'ye göre, müsin birikimi ve bazal membran kalınlaşması DLE'de Rozasea ve PIE'ye göre anlamlı olarak daha fazla izlendi. İmmunhistokimyasal bulgulardan CD123 oranları açısından vaka grupları arasında istatiksel olarak anlamlı fark tespit edildi (p=0,006). Vakalarda izlenen CD123 oranları açısından bu anlamlılık değeri Rozasea ve DLE arasından kaynaklandığı (p=0,005) izlendi. Buna göre DLE'de CD123+ plazmositoid dentritik hücre oranları Rozasea'ya göre anlamlı derecede yüksek bulundu. Ayrıca en az CD123+ 20 hücreli grup içeren vaka sayıları açısından anlamlı bir fark tespit edildi (p=0,005). Bu anlamlı farkı DLE'de PIE ve Rozasea'ya göre daha fazla en az CD123+ 20 hücreli grup içermesi oluşturmaktadır. CD4/CD8 oranları açısından vaka v grupları arasında istatiksel olarak anlamlı fark tespit edilmedi (p=0,058). P değerinin 0.05'in hafif üstünde olması dikkati çekti. Sonuç: Bu çalışmamızda DLE, PIE ve Rozasea vakalarında histopatolojik ayrımda folliküler plugging, Demodeks varlığı, ödem, spongioz, müsin birikimi, bazal membran kalınlaşması gibi histolojik bulguların vurgulanması yanısıra histopatolojik ayrımda zorlandığımız vakalarda immunhistokimyasal bulgulardan CD123 oranının DLE ile Rozasea ayrımında bir seçenek olarak kullanılabileceği kanaatine varılmıştır. Yine en az CD123+ 20 hücreli grup içerip içermemesi DLE'yi PIE ve Rozasea'dan ayırımında kullanılabileceği düşünülmüştür.Rosacea, discoid lupus erythematosus (DLE) and Polymorphic Light Eruption (PLE) are lesions with similar findings both clinically and histopathologically. In this study, we aimed to compare the immunohistochemically CD123 ratio with the presence of PDH and CD4 / CD8 ratios in lymphocytes with histopathological analysis in all three lesions, thus investigating the contribution of immunohistochemistry in reaching the correct diagnosis and contributing to the literature. Method: The preparations of 27 DLE, 27 PLE and 29 Rosacea cases who were examined and diagnosed in the laboratory of the Department of Pathology of Meram Medical Faculty between 2015-2020 were reviewed histopathologically. Sections were taken from the paraffin blocks, CD4, CD8 and CD123 staining was performed on an immunohistochemical stainer, CD4 / CD8 ratios of lymphocytic infiltrations in the lesions and CD123 positive PDH rates were evaluated. Results were listed according to patient groups and statistical consistency and differences were revealed. Results: In the statistical results, a significant difference was found between the cases in terms of histopathological findings such as follicular plugging, presence of demodex, edema, spongiosis, mucin accumulation, basement membrane thickening (respectively; p = 0.003; p = <0.001; p = 0.001; p = 0.027; p = <0.001; p = <0.001). Demodex presence was significantly more observed in Rozasea than in PLE and DLE, edema and spongiosis in PLE than in DLE, follicular plugging in DLE and Rozasea than in PLE, mucin accumulation and basal membrane thickening were significantly more observed in DLE than in Rozasea and PLE. A statistically significant difference was found between the case groups in terms of CD123 rates among immunohistochemical findings (p = 0.006). It was observed that this significance value in terms of CD123 rates observed in cases originated from Rosacea and DLE (p = 0.005). Accordingly, the rates of CD123 + plasmacytoid dendritic cells in DLE were found to be significantly higher than Rosacea. In addition, a significant difference was vii found in terms of the number of cases with at least CD123 + 20 cell groups (p = 0.005). This significant difference is due to the fact that it contains more CD123 + 20-cell groups in DLE than PLE and Rosacea. There was no statistically significant difference between the case groups according to the order of CD4 / CD8 (p = 0.058). It was noteworthy that the p value was slightly above 0.05. Conclusion: In this study, in the histopathological distinction of DLE, PLE and Rosacea cases, in addition to emphasizing histological findings such as follicular plugging, presence of Demodex, edema, spongiosis, mucin accumulation, basement membrane thickening, it was concluded that the CD123 ratio from immunohistochemical findings can be used as an option in distinguishing DLE from Rosacea. It is thought that whether it contains at least CD123 + 20-cell group or not can be used to distinguish DLE from PLE and Rosacea
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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