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Objective: Hungary has repeatedly been shown to have the highest cancer-related mortality and incidence in Europe. Despite lung cancer being the most abundant malignant diagnosis in Hungary, numerous concerns have been raised recently regarding the bias inherent to reported incidence estimates. Re-analysis of reimbursement claims has been suggested previously by our group as an alternative approach, offering revised figures of lung cancer incidence between 2011 and 2016. Leveraging on this methodology, we aimed at updating Hungarian lung cancer incidence estimates with an additional 5 years (2017-2021), including years affected by the COVID-19 pandemic. Additionally, we also attempted to improve the robustness of estimates by taking additional characteristics of the patient pathway into account., Methods: Lung cancer patients between 2011 and 2021 were identified based on reimbursement-associated ICD-10 codes, histology codes and time patterns. Multiple query architectures were tested for sensitivity and compared to official estimates of the Hungarian National Cancer Registry (HNCR). Epidemiological trends were estimated by Poisson-regression, corrected for age and sex., Results: A total of 89,948 lung cancer patients diagnosed in Hungary between 2011 and 2021 have been identified by our study. In 2019 alone, 7,887 patients were diagnosed according to our optimized query. ESP2013 standardized rate was estimated between 92.5/100,000 (2011) and 78.4/100,000 (2019). In 2019, standardized incidence was 106.8/100,000 for men and 59.7/100,000 for women. Up until the COVID-19 pandemic, lung cancer incidence was decreasing by 3.18% (2.1%-4.3%) yearly in men, while there was no significant decrease in women. Young age groups (40-49 and 50-59) featured the largest improvement, but women aged 60-79 are at an increasing risk for developing lung cancer. The COVID-19 pandemic resulted in a statistically significant decrease in lung cancer incidence, especially in the 50-59 age group (both sexes)., Conclusion: Our results show that using an optimized approach, re-analysis of reimbursement claims yields robust estimates of lung cancer incidence. According to this approach, the incidence rate of male lung cancer is declining in Hungary, in concordance with the trend observed for lung cancer mortality. Among women aged 60-79, the incidence of lung cancer has risen, requiring more attention in the near future., Competing Interests: GS, GH, ÉB, and KK are employees of MSD Pharma Hungary Ltd. ZV is an employee of Semmelweis University where his contribution to this project was financially compensated. ZKis is also an employee of MSD Pharma Hungary Ltd. and has an affiliation at the Second Department of Medicine and Nephrology-Diabetes Center, University of Pécs Medical School, Pécs, Hungary. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. The project was financed by MSD Pharma Hungary Ltd. VM has received consultation fees from AstraZeneca, Boehringer Ingelheim, Roche, Berlin-Chemie, Chiesi, BMS, Novartis, Actelion, Gilead, Pfizer, Richter, Lilly, Orion Pharma and Ipsen and served as PI for over 10 LC studies. LT is an employee of Semmelweis University. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gálffy, Szabó, Tamási, Müller, Moldvay, Sárosi, Kerpel-Fronius, Kardos, Csada, Pápai-Székely, Szász, Király, Hódi, Kovács, Balogh, Kovács, Darida, Buga, Rokszin, Abonyi-Tóth, Kiss, Vokó and Bogos.)

Objectives: The introduction of low-dose CT (LDCT) altered the landscape of lung cancer (LC) screening and contributed to the reduction of mortality rates worldwide. Here we report the final results of HUNCHEST-II, the largest population-based LDCT screening program in Hungary, including the screening and diagnostic outcomes, and the characteristics of the LC cases., Methods: A total of 4215 high-risk individuals aged between 50 and 75 years with a smoking history of at least 25 pack-years were assigned to undergo LDCT screening. Screening outcomes were determined based on the volume, growth, and volume doubling time of pulmonary nodules or masses. The clinical stage distribution of screen-detected cancers was compared with two independent practice-based databases consisting of unscreened LC patients., Results: The percentage of negative and indeterminate tests at baseline were 74.2% and 21.7%, respectively, whereas the prevalence of positive LDCT results was 4.1%. Overall, 76 LC patients were diagnosed throughout the screening rounds (1.8% of total participants), out of which 62 (1.5%) patients were already identified in the first screening round. The overall positive predictive value of a positive test was 58%. Most screen-detected malignancies were stage I LCs (60.7%), and only 16.4% of all cases could be classified as stage IV disease. The percentage of early-stage malignancies was significantly higher among HUNCHEST-II screen-detected individuals than among the LC patients in the National Koranyi Institute of Pulmonology's archive or the Hungarian Cancer Registry (p < 0.001)., Conclusions: HUNCHEST-II demonstrates that LDCT screening for LC facilitates early diagnosis, thus arguing in favor of introducing systematic LC screening in Hungary., Clinical Relevance Statement: HUNCHEST-II is the so-far largest population-based low-dose CT screening program in Hungary. A positive test's overall positive predictive value was 58%, and most screen-detected malignancies were early-stage lesions. These results pave the way for expansive systematic screening in the region., Key Points: • Conducted in 18 medical facilities, HUNCHEST-II is the so far largest population-based low-dose CT screening program in Hungary. • The vast majority of screen-detected malignancies were early-stage lung cancers, and the overall positive predictive value of a positive test was 58%. • HUNCHEST-II facilitates early diagnosis, thus arguing in favor of introducing systematic lung cancer screening in Hungary., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: The approval of immunotherapy (I-O) for the treatment of late-stage non-small cell lung cancer (NSCLC) opened new perspectives in improving survival outcomes. However, survival data have not yet been provided from the period of the Covid-19 pandemic. The aims of our study were to assess and compare survival outcomes of patients with advanced LC receiving systemic anticancer treatment (SACT) before and after the approval of immunotherapy in Hungary, and to examine the impact of pandemic on survival outcomes using data from the Hungarian National Health Insurance Fund (NHIF) database., Methods: This retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with advanced stage lung cancer (LC) (ICD-10 C34) between 1 January 2011 and 31 December 2021 and received SACT treatment without LC-related surgery. Survival rates were evaluated by year of diagnosis, sex, age, and LC histology., Results: In total, 35,416 patients were newly diagnosed with advanced LC and received SACT during the study period (mean age at diagnosis: 62.1-66.3 years). In patients with non-squamous cell carcinoma, 3-year survival was significantly higher among those diagnosed in 2019 vs. 2011-2012 (28.7% [95% CI: 26.4%-30.9%] vs. 14.45% [95% CI: 13.21%-15.69%], respectively). In patients with squamous cell carcinoma, 3-year survival rates were 22.3% (95% CI: 19.4%-25.2%) and 13.37% (95% CI: 11.8%-15.0%) in 2019 and 2011-2012, respectively, the change was statistically significant. Compared to 2011-2012, the hazard ratio of survival change for non-squamous cell carcinoma patients was 0.91, 0.82, and 0.62 in 2015-2016, 2017-2018, and 2019, respectively (p<0.001 for all cases). In the squamous cell carcinoma group, corresponding hazard ratios were 0.93, 0.87, and 0.78, respectively (p<0.001 for all cases). Survival improvements remained significant in both patient populations during the Covid-19 pandemic (2020-2021). No significant improvements were found in the survival of patients with small cell carcinoma. Platinum-based chemotherapy was the most common first-line treatment in all diagnostic periods, however, the proportion of patients receiving first- or second-line immunotherapy significantly increased during the study period., Conclusion: 3-year survival rates of NSCLC almost doubled among patients with non-squamous cell carcinoma and significantly improved at squamous cell carcinoma over the past decade in Hungary. Improvements could potentially be attributable by the introduction of immunotherapy and were not offset by the Covid-19 pandemic., Competing Interests: GH, KKn, TS, ZP and KKo are employees of MSD Pharma Hungary Ltd. ZV is an employee of Semmelweis University where their contribution to this project was financially compensated. ZKis is also employee of MSD Pharma Hungary Ltd., and has affiliation at Second Department of Medicine and Nephrology-Diabetes Center, University of Pécs Medical School, Pécs, Hungary. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. ZB is employee of Syntesia Ltd. and her contribution to this project was financially compensated. The program is financed by MSD Pharma Hungary Ltd. VM has received consultation fees from Astraeneca, Boehringer Ingelheim, Roche, Berlin-Chemie, Chiesi, BMS, Novartis, Actelion, Gilead, Pfizer, Richter, Lilly, Orion Pharma and Ipsen and served as PI for over 10 LC studies. LT is employee of Semmelweis University. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kiss, Gálffy, Müller, Moldvay, Sárosi, Pápai-Székely, Csada, Kerpel-Fronius, Király, Szász, Hódi, Polányi, Kovács, Karamousouli, Knollmajer, Szabó, Berta, Vokó, Rokszin, Abonyi-Tóth, Barcza, Tamási and Bogos.)

Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease with various clinical forms, including the subtypes of discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). The altered function of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis in CLE pathogenesis has been suggested. Here, the soluble forms of PD-1 (sPD-1) and PD-L1 (sPD-L1) were explored in untreated DLE and SCLE. Levels of sPD-1 and sPD-L1 were determined by enzyme-linked immunosorbent assay in serums of 21 DLE, 18 SCLE, 13 systemic lupus erythematosus (SLE) patients and 20 healthy controls (HCs). Differences between patient groups and HCs, and the association between clinical activity of skin symptoms and sPD-1/sPD-L1 levels were analyzed with Mann-Whitney U-test and Spearmann's correlation. Regarding sPD-1 levels, no statistically significant differences were found between DLE and SCLE groups, nor compared to HCs. As for sPD-L1, a significantly lower level was found in the DLE group compared to the SCLE and HC groups ( p = 0.027 and p = 0.009, respectively). In SLE, significantly higher sPD-1 was found compared to HCs ( p = 0.002). No association between skin symptom activity and sPD-1/sPD-L1 levels was found in CLE. Alterations of the inhibitory effect of sPD-L1 on T-cell activity might elucidate the differences between DLE and SCLE.

Dermoscopy is an easily accessible, noninvasive diagnostic tool, originally used in the differentiation of benign and malignant skin tumors. Other structures beside pigment content observed by dermoscopy, e.g., scaling, follicles, or vessels, may present in a specific pattern in different dermatoses. Recognition of these patterns may aid the diagnosis of inflammatory and infectious dermatological conditions. The aim of this article is to review the distinct dermoscopic features of granulomatous and autoimmune skin diseases. Diagnosis of granulomatous skin disorders is based on the histopathological examination. The dermoscopic picture of these diseases (cutaneous sarcoidosis, granuloma annulare, necrobiosis lipoidica, and granulomatous rosacea) show many similarities; however, there are some differences to note between the dermatoses, mainly in granuloma annulare. The cornerstones of the diagnostic process of autoimmune skin diseases (morphea, systemic sclerosis, dermatomyositis, cutaneous lupus erythematosus) include the clinical picture, immunoserology, and histology; however, dermoscopy may aid the diagnostic process and follow-up of the patients. For those diseases, where vascular abnormalities play an important role in the pathogenesis, videocapillaroscopy is used for examination of the microcirculation at the nailfold capillaries. Dermoscopy can be an easy-to-use everyday diagnostic tool in clinical practice regarding granulomatous and autoimmune skin diseases. Although punch biopsy is inevitable in many cases, the distinct dermoscopic structures can aid the diagnostic process., (© 2023. The Author(s).)

Introduction: Lupus erythematous panniculitis (LEP) is a rare type of chronic cutaneous lupus erythematous. Clinical characteristics are tender, subcutaneous nodules, erythematous plaques. Disfigurement of face and body might develop which affects the patient's quality of life. LEP can be the first sign of systemic lupus erythematous (SLE)., Objective: Our aim was to review the clinicopathological characteristics and the course of LEP through our own patients., Methods: We retrospectively analyzed the clinical records of 17 LEP patients at Semmelweis University's Department of Dermatology, Venerology and Dermatooncology between 2000 and 2022., Results: The male : female ratio was 1 : 16, average age was 37.8 years. Lesion localisations were proximal lower (8/17) and upper extremities (7/17), face (4/17), breast (3/17), chest (2/17), buttocks (2/17), back (1/17) and distal lower extremity (1/17). Lesion morphologies were nodules (11/17), plaques (7/17), lipoatrophy (4/17), ulceration (3/17), calcification (1/17). Discoid changes covered in 6 cases. In 10 cases, systemic symptoms were observed (arthritis (4/17), haematological (5/17), renal (2/17), anti-phospholipid syndrome (2/17). 7 patients fulfilled the EULAR/ACR criteria for SLE. Histology showed mixed type panniculitis in 8, lobular in 3 cases. Average time until diagnosis was 24.3 months. Among all our SLE patients, skin symptoms regressed following systemic immunosuppressive treatment. LEP patients with only skin manifestation were often resistant for the therapy of cutaneous lupus erythematous., Conclusion: The diagnosis of LEP often takes months or years. Wider knowledge of LEP would shorten the time to diagnosis, preventing disfigurement and possible damage of internal organs. Based on our observations, LEP without SLE might be treated with early immunosuppression. Orv Hetil. 2023; 164(5): 172-178.

The pathomechanism of various autoimmune diseases is known to be associated with the altered function of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. We aimed to investigate the role of this pathway and inflammatory cell markers in subtypes of cutaneous lupus erythematosus (CLE): discoid lupus erythematosus (DLE), subacute CLE (SCLE) and toxic epidermal necrolysis (TEN)-like lupus, a hyperacute form of acute CLE (ACLE). Ten skin biopsy samples from 9 patients were analyzed with immunohistochemistry regarding the following markers: CD3, CD4, CD8, Granzyme B, CD123, CD163, PD-1, PD-L1. Our group consisted of 4 SCLE (2 idiopathic (I-SCLE) and 2 PD-1 inhibitor-induced (DI-SCLE)), 4 DLE and 1 TEN-like lupus cases. From the latter patient two consecutive biopsies were obtained 1 week apart. Marker expression patterns were compared through descriptive analysis. Higher median keratinocyte (KC) PD-L1 expression was observed in the SCLE group compared to the DLE group (65% and 5%, respectively). Medians of dermal CD4, Granzyme B (GB), PD-1 positive cell numbers and GB+/CD8 + ratio were higher in the DLE group than in the SCLE group. The I-SCLE and DI-SCLE cases showed many similarities, however KC PD-L1 expression and dermal GB positive cell number was higher in the former. The consecutive samples of the TEN-like lupus patient showed an increase by time within the number of infiltrating GB+ cytotoxic T-cells and KC PD-L1 expression (from 22 to 43 and 30%-70%, respectively). Alterations of the PD-1/PD-L1 axis seems to play a role in the pathogenesis of CLE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Király, Szepesi, Sebestyén, Kuroli, Rencz, Tóth, Bokor, Szakonyi, Medvecz and Hidvégi.)