Higher neoantigen load correlates with better overall survival in Chinese lung adenocarcinoma patients

Introduction. Neoantigen load (NAL) has been extensively studied as a promising biomarker for immunotherapy. Recently it was also reported that NAL is associated with lung cancer patient survival, but the results were not consistent. Material and methods. To further evaluate the prognostic value of NAL in lung cancer, we analyzed NAL in a cohort of 96 lung adenocarcinoma (AD) and 83 lung squamous cell carcinoma (SQ) patients from the Cancer Genome Atlas (TCGA). We found that high NAL correlates with better overall survival (OS) of AD patients but with worse OS of SQ patients. Next, we collected a total of 25 NSCLC patient samples and explored whole exome sequencing (WES) and a large targeted gene panel (Med1CDx panel containing 579 genes) for NAL and tumor mutation burden (TMB) analysis. Results. We found that patients with both higher NAL and TMB, who underwent chemotherapy combined with immunotherapy, showed better OS and progression-free survival (PFS) in both AD and SQ subgroups. We also compared the concordance of NAL and TMB between WES and the Med1CDx panel. The R2 for concordance of NAL and TMB prediction by WES and our Med1CDx panel was 0.81 and 0.86, respectively. Conclusions. In this study, we showed that NAL is a useful biomarker for lung cancer OS prediction at least in the AD cohort. Furthermore, considering the high cost ofWES, large targeted gene-panel-based NAL and TMB analysis could be a good alternative in clinical practical settings

Malignant peripheral nerve sheath tumor—from genetics to multidisciplinary treatment

Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma (STS); it originates from nervous tissue and typically develops in proximity to nerve trunks in the limbs and trunk. These tumors, constituting approximately 5% of soft tissue sarcomas, can either form spontaneously or arise frompre-existing neurofibromas. The majority (90%) of cases occur in individuals between the 2nd and 5th decades of life. Themain risk factor for MPNST is von Recklinghausen disease (type 1 neurofibromatosis). The cornerstone of MPNST management involves radical surgicalmeasures, specifically tumor excision within healthy tissue boundaries (wide local excision), which is complemented by adjuvant radiotherapy. In case of metastatic disease, palliative chemotherapy employing doxorubicin or a combination of doxorubicin and ifosfamide is utilized. Approximately 25–30% of patients experience clinical improvement after chemotherapy. Looking ahead, advancements in research on molecular biology may lead to the development of inhibitors demonstrating greater efficacy than traditional chemotherapy for MPNST patients. At present, ongoing clinical trials of the therapeutic management of MPNST encompass pembrolizumab, the combination of nivolumab with ipilimumab, pexydartinib (an inhibitor targeting KIT, CSF1R, and FLT3) in conjunction with sirolimus, sapanisertib (a TORC1/2 inhibitor), or LOXO-195 (an inhibitor of neurotrophic tyrosine kinase receptors NTRK type 1, 2, and 3)

Psychological features of cyberbullying in adolescents

Introduction: The article is devoted to the study of the socio-psychological features of cyberbullying in adolescents, namely the determination of the factors that cause this phenomenon, and the study of the nature of their relationships. Material and methods: The study was used socio-demographic questionnaire, the European Cyberbullying Intervention Project Questionnaire (ECIP-Q), the Rosenberg Self-Esteem Scale (RSES), Pochebut’s aggression questionnaire, the UCLA Loneliness Scale, and the Lie Scale from the Eysenck Personality Questionnaire-Revised (EPQ-R); Google Forms. Discussion: However, the presence of siblings acts as a protective factor, reducing victimization. Emotional aggression and the experience of aggression on the Internet turned out to be direct predictors of aggression during cyberbullying. In particular, certain types of online activity or behavior significantly increased the risk of the aggressor’s role in cyberbullying. At the same time, emotional aggression and self-perception of behavior on the Internet are particularly highlighted as strong factors of influence. Results: Thus, the results of the study suggest that both personal and contextual factors play a crucial role in determining how people express themselves in cyberbullying — as victims or as aggressors. Conclusions: The protective role of siblings in the context of cyberbullying must be taken into account when developing prevention strategies for this phenomenon. Understanding adolescent cyberbullying and its psychological features is important to develop effective strategies to counteract this phenomenon and provide psychological support for victims and aggressors

Partnerstwo z pacjentem — czy może być pomocne w zwiększeniu stopnia stosowania się do zaleceń terapeutycznych w chorobach układu sercowo‑naczyniowego?

Wysiłki mające na celu zwiększenie przestrzegania zaleceń terapeutycznych w prewencji pierwotnej i wtórnej chorób sercowo-naczyniowych (s-n) koncentrują się na poprawie komunikacji między pacjentami a lekarzami. Lekarze muszą promować edukację pacjentów i zwalczać dezinformację dostępną w Internecie. Pomocne może być również wykorzystanie metod elektronicznych (np. przypomnienia SMS), eliminacja barier ekonomicznych i monitorowanie przestrzegania zaleceń. W odniesieniu do farmakoterapii, uproszczenie schematów leczenia za pomocą szeroko stosowanych preparatów złożonych (SPC) może stanowić skuteczny środek do znacznej poprawy przestrzegania zaleceń. Tylko kompleksowe wysiłki na rzecz poprawy przestrzegania zaleceń poprzez budowanie partnerskich relacji pacjent–lekarz mogą przyczynić się do zwiększenia wytrwałości i doprowadzić do zmniejszenia zachorowalności i śmiertelności z przyczyn s-n w populacji ogólnej

CCL19 promotes TNF-alpha/IFN-gamma-induced production of cytokines by targeting CCR7/NF-κB signalling in HaCaT cells

Introduction. Atopic dermatitis (AD) is the most common allergic skin disease. The dysfunction of keratinocytes is closely associated with AD progression. Nevertheless, the specific functions of CC chemokine ligand 19 (CCL19) and its receptor CC chemokine receptor 7 (CCR7) in human HaCaT keratinocytes are still unclear. Material and methods. AD cell models in vitro were established by treating HaCaT cells with TNF-alpha (TNF-α, 10 ng/mL) and IFN-gamma (IFN-γ, 10 ng/mL). Cell viability was estimated by MTT assay. The protein levels of CCL19 and CCR7 were tested via Western blotting. The expression of CCL19 protein was knocked down by transfecting si-CCL19 into HaCaT cells. The contents of inflammatory factors i.e. thymus and activation-regulated chemokine (TARC), interleukin 6 (IL-6), and prostaglandin E2 were measured by ELISA, and the nitric oxide content was detected by Griess reagent. The protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were tested via Western blotting. Results. TNF-α and IFN-γ induced cytotoxicity and upregulated the expression of CCL19 and CCR7 in HaCaT cells. CCL19 knockdown alleviated cytokines-induced cytotoxicity and the release of TARC, IL-6, PGE2 and nitric oxide in TNF-α + IFN-γ-treated HaCaT cells. Furthermore, the protein levels of iNOS and COX-2 were also repressed by CCL19 knockdown. In addition, knockdown of CCL19 decreased CCR7 protein content and inhibited the phosphorylation of IκBα and p65, implying that knockdown of CCL19 inactivated CCR7/NF-κB signalling in HaCaT cells. Rescue assays validated that CCR7 overexpression reversed the effects of CCL19 silencing on the viability and levels of inflammatory factors in TNF-α + IFN-γ-induced HaCaT cells. Conclusions. This study proves that CCL19 can promote TNF-α + IFN-γ-induced skin inflammatory responses by targeting CCR7/NF-κB pathway in HaCaT cells

Przemyślany wybór miejsca biopsji — przydatność dermoskopii w diagnostyce choroby Bowena w obrębie twarzy

Precyzyjna ocena zmian w obrębie fotouszkodzeń skóry twarzy może być dużym wyzwaniem. Nie jest rzadkością kolidowanie ze sobą zmian łagodnych, przednowotworowych i złośliwych. Fundamentalne znaczenie dla ustalenia właściwego rozpoznania ma wybór miejsca biopsji; w związku z tym biopsje nie powinny być pobierane w sposób przypadkowy, ale należy je poprzedzić szczegółową oceną wstępną, w szczególności oceną dermoskopową. W artykule przedstawiono przypadek 78-letniej pacjentki, u której wykonana pod kontrolą dermoskopii biopsja nieregularnej blaszki rumieniowej doprowadziła do rozpoznania raka kolczystokomórkowego in situ

Whole exome sequencing-based testing of adult epilepsy in a Polish population

Aim of the study. Genetic panel testing in paediatric and mixed adult and children populations has demonstrated clinical utility and provided a diagnostic yield of 18–40%. The data on adult epilepsies is limited. We aimed to investigate the diagnostic yield and analyse genetic diagnoses in whole exome sequenced adult patients with epilepsies in Poland. Material and methods. We recruited 151 patients from 42 clinical centres across Poland. The patients had a diagnosis of epilepsy/ seizures, were 18 or older at the time of the genetic testing, and did not have a genetic diagnosis. All patients were tested with whole exome sequencing after an initial testing with a panel of 47 epilepsy-related genes. Results. We reached a diagnostic yield when considering pathogenic/probably pathogenic variants according to ClinVar of 8.6% (n = 13) and 17% (n = 26) when applying the American College of Medical Genetics (ACMG) criteria. Most patients had a pathogenic/probably pathogenic variant in epilepsy-related genes (54%), followed by potential epilepsy-related genes (19%), and neurodevelopment-associated epilepsy genes (15%). Conclusions. Our study shows that whole exome sequencing-based testing reaches a slightly higher diagnostic yield that the traditional 300 gene panel. Genes related to childhood onset neurodevelopmental disorders and epilepsy should be considered as well. Clinical implications/future directions. Patients may have had a diagnosis related to a childhood syndrome, but due to limited diagnostic possibilities, it was not possible to diagnose them in childhood. We would consider testing adult patients with epilepsy with whole exome or genome sequencing (or if not possible with a panel) in cases of a diagnosis of epilepsy with no hints suggesting secondary epilepsy, and especially with clinical features indicating a genetic epilepsy diagnosis, such as neurodevelopmental delay and early onset of seizures

Mężczyzna w wieku 71 lat z przewlekłym bólem barku

Praca przedstawia opis przypadku mężczyzny w wieku 71 lat, z rozpoznanym rakiem niedrobnokomórkowym szczytu prawego płuca.Obejmuje specyfikę symptomatologii i diagnostyki, zarówno obrazowej, jak i inwazyjnej guza Pancoasta, a także diagnostykęróżnicową zmian ogniskowych zlokalizowanych w obrębie szczytów płuc. Praca ma na celu zwrócenie uwagi na guza płuca jakomożliwą przyczynę przewlekłego bólu barku