Impact of COVID-19 Pandemic on Disease Control Status and Quality of Life of Patients with Acromegaly

Background and Objectives: Despite the best efforts of healthcare workers and the deployment of alternative healthcare delivery solutions through telemedicine, the pandemic has disrupted standard care for patients with chronic conditions. The long-lasting pandemic has also had a profound impact on the quality of life (QoL) of the majority of patients with chronic illnesses. The management of rare diseases has been particularly challenging. We aimed to evaluate the impacts that the long-lasting pandemic had on the disease control status and QoL in patients with acromegaly. Materials and Methods: Our prospective study included 34 patients from a national referral centre. The baseline SAGIT and AcroQoL results were obtained in October 2020 during the lockdown period of the SARS-CoV2 pandemic. The follow-up results were assessed during the summer of 2022 in a period without any public health restrictions. All the patients were additionally evaluated for their attitude towards preventative public health measures against SARS-CoV2 spread and required mask wearing during the pandemic. Results: By comparing assessments in 2020 during the lockdown period and 2022 post-lockdown, we observed some improvement in SAGIT subscores T and I, most likely reflecting treatment changes in a small number of patients. The global SAGIT score remained stable. QoL measurement by AcroQoL did not demonstrate any changes. There was a negative correlation between SAGIT subscore S and the AcroQoL results. We also noted that the group of patients with the most negative attitude toward public health measurements for preventing SARS-CoV2 spread had higher AcroQoL results than others. Conclusion: Our results showcase that the SARS-CoV2 pandemic, lasting over two years, did not impact the disease control status and QoL in patients with acromegaly. The cohort continued to be well controlled and without changes in QoL. We measured a relatively favourable attitude towards the public health measures to prevent the spread of SARS-CoV2; in particular, patients who had a lower QoL had more positive attitudes towards these measures

Current Mesothelioma Treatment and Future Perspectives

The established treatments in malignant mesothelioma are based on trimodality approach including surgery, radiation and chemotherapy. Such approach has proved to clinically benefit mesothelioma patients, however the current treatments seem to have reached a limit regarding the survival and disease control. One approach to overcome the limitations of current treatments is focused on finding appropriate serum or genetic biomarkers that could support personalized medicine and improve outcomes with established treatment modalities in mesothelioma patients. The other approach is exploiting better understanding of molecular and genetic characteristics of mesothelioma to search for new treatment modalities. Immunotherapy with anti PD-1, PD-L1 and CTLA-4 agents is a new frontier in mesothelioma treatment. As in many solid tumors, CAR-T cell therapy is emerging from the field of hematological malignancies. Immunomodulatory approaches seem to be a new perspective in treatment of malignant mesothelioma. This chapter aims to explore possible new therapeutic approaches in mesothelioma

Vpliv genetske variabilnosti v poteh homologne rekombinacije na odgovor na zdravljenje z obsevanjem pri raku dojk

Rak dojk je heterogena bolezen, ki jo lahko zdravimo kirurško, s sistemsko terapijo in z obsevanjem. Dopolnilno obsevanje bolnic z rakom dojk pomembno vpliva na preživetje, a povzroča tudi neželene učinke zdravljenja. V obsevalno polje namreč ne moremo zajeti zgolj tumorskih celic, temveč zajamemo tudi celice zdravih tkiv. Neželeni učinki zdravljenja z obsevanjem so pri bolnikih z enako shemo zdravljenja različni, eden od vzrokov za ta pojav pa je tudi genetska variabilnost. Obsevanje povzroča napake na DNK tumorskih celic in vodi v celično smrt tumorskih celic. Najnevarnejša poškodba DNK, ki nastane ob izpostavitvi sevanju, je dvojni prelom. Popravi se lahko s homologno rekombinacijo. Kadar je zaradi spremenjenega genskega zapisa za proteine, ki sodelujejo v poteh popravljanja DNK, spremenjeno izražanje gena ali delovanje proteina, se to lahko kaže v različni stopnji uspešnega popravljanja napak DNK, slednje pa v različnem odgovoru na zdravljenje. V prispevku je podrobneje opisana povezava med polimorfizmi v genih, ki sodelujejo v poteh homologne rekombinacije: RAD51 rs1801320 ter rs1801321 in XRCC3 rs861539 ter rs1799794, in odgovorom na zdravljenje z obsevanjem pri raku dojk

Extracellular Vesicle Enriched miR-625-3p Is Associated with Survival of Malignant Mesothelioma Patients

Malignant mesothelioma (MM) is characterized by poor prognosis and short survival. Extracellular vesicles (EVs) are membrane-bound particles released from cells into various body fluids, and their molecular composition reflects the characteristics of the origin cell. Blood EVs or their miRNA cargo might serve as new minimally invasive biomarkers that would enable earlier detection of MM or treatment outcome prediction. Our aim was to evaluate miRNAs enriched in serum EVs as potential prognostic biomarkers in MM patients in a pilot longitudinal study. EVs were isolated from serum samples obtained before and after treatment using ultracentrifugation on 20% sucrose cushion. Serum EV-enriched miR-103-3p, miR-126-3p and miR-625-3p were quantified using qPCR. After treatment, expression of miR-625-3p and miR-126-3p significantly increased in MM patients with poor treatment outcome (p = 0.012 and p = 0.036, respectively). A relative increase in miR-625-3p expression after treatment for more than 3.2% was associated with shorter progression-free survival (7.5 vs. 19.4 months, HR = 3.92, 95% CI = 1.20–12.80, p = 0.024) and overall survival (12.5 vs. 49.1 months, HR = 5.45, 95% CI = 1.06–28.11, p = 0.043) of MM patients. Bioinformatic analysis showed enrichment of 33 miR-625-3p targets in eight biological pathways. Serum EV-enriched miR-625-3p could therefore serve as a prognostic biomarker in MM and could contribute to a more personalized treatment

NBN, RAD51 and XRCC3 Polymorphisms as Potential Predictive Biomarkers of Adjuvant Radiotherapy Toxicity in Early HER2-Positive Breast Cancer

Radiotherapy (RT) for breast cancer significantly impacts patient survival and causes adverse events. Double-strand breaks are the most harmful type of DNA damage associated with RT, which is repaired through homologous recombination (HRR). As genetic variability of DNA repair genes could affect response to RT, we aimed to evaluate the association of polymorphisms in HRR genes with tumor characteristics and the occurrence of RT adverse events in early HER2-positive breast cancer. Our study included 101 breast cancer patients treated with adjuvant RT and trastuzumab. All patients were genotyped for eight single nucleotide polymorphisms in NBN, RAD51 and XRCC3 using competitive allele-specific PCR. Carriers of XRCC3 rs1799794 GG genotype were less likely to have higher tumor differentiation grade (OR = 0.05, 95% CI = 0.01–0.44, p = 0.007). Carriers of RAD51 rs1801321 TT genotype were more likely to have higher NYHA class in univariable (OR = 10.0; 95% CI = 1.63–61.33; p = 0.013) and multivariable (OR = 9.27; 95% CI = 1.28–67.02; p = 0.027) analysis. Carriers of RAD51 rs12593359 GG genotype were less likely to have higher NYHA class in univariable (OR = 0.09; 95% CI = 0.01–0.79; p = 0.030) and multivariable (OR = 0.07; 95% CI = 0.01–0.81; p = 0.034) analysis. Carriers of XRCC3 rs1799794 GG genotypes experienced more skin adverse events based on LENT-SOMA scale in univariable (OR = 5.83; 95% CI = 1.22–28.00; p = 0.028) and multivariable (OR = 10.90; 95% CI = 1.61–73.72; p = 0.014) analysis. In conclusion, XRCC3 and RAD51 polymorphisms might contribute to RT adverse events in early HER2-positive breast cancer patients