What medical conditions lead to a request for euthanasia? A rapid scoping review.

Background and Aims: Euthanasia is a controversial issue related to the right to die. Although euthanasia is mostly requested by terminally sick individuals, even in societies where it is legal, it is unclear what medical conditions lead to euthanasia requests. In this scoping review, we aimed to compile medical conditions for which euthanasia has been requested or performed around the world. Methods: The review was preferred reporting items for systematic reviews and meta-analysis for scoping reviews (PRISMA-ScR) checklist. Retrieved search results were screened and unrelated documents were excluded. Data on reasons for conducting or requesting euthanasia along with the study type, setting, and publication year were extracted from documents. Human development index and euthanasia legality were also extracted. Major medical fields were used to categorize reported reasons. Group discussions were conducted if needed for this categorization. An electronic search was undertaken in MEDLINE through PubMed for published documents covering the years January 2000 to September 2022. Results: Out of 3323 records, a total of 197 papers were included. The most common medical conditions in euthanasia requests are cancer in a terminal phase (45.4%), Alzheimer's disease and dementia (19.8%), constant unbearable physical or mental suffering (19.8%), treatment-resistant mood disorders (12.2%), and advanced cardiovascular disorders (12.2%). Conclusion: Reasons for euthanasia are mostly linked to chronic or terminal physical conditions. Psychiatric disorders also lead to a substantial proportion of euthanasia requests. This review can help to identify the features shared by conditions that lead to performing or requesting euthanasia.

Reduced Expression of Natural Killer Cell-Related Activating Receptors by Peripheral Blood Mononuclear Cells from Patients with Breast Cancer and Their Improvement by Zoledronic Acid.

BACKGROUND/AIM: Natural killer (NK) cell receptors affect the NK cell-mediated elimination of malignant cells. In this experimental study the effect of Zoledronic acid (ZOL) was investigated on the expression of NK activating- (NKP46 and NKG2D) and inhibitory (KIR2DL1) receptors by Phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from breast cancer (BC) patients. MATERIALS AND METHODS: Peripheral blood mononuclear cell-extracted RNA from thirty breast cancer women and twenty-five healthy subjects was analyzed for gene expression of NKP46, NKG2D and KIR2DL1 using real time-PCR. Then, the PBMCs from BC patients were cultured in the presence of PHA with 5 µg/ml, 10 or 20 µg/ml of ZOL for 32 hours and expression of the aforementioned receptors was determined. RESULTS: Expression of NKP46, NKG2D and NKP46/KIR2DL1 ratio in BC women were lower than healthy group (P<0.01, P<0.04 and P<0.05, respectively). NKP46 expression was up-regulated by PHA-stimulated PBMCs treated with 10 µg/ml and 20 µg/ml of ZOL compared with PHA-stimulated cultures (P<0.01 and P<0.05, respectively). NKG2D expression remarkably increased by PHA-stimulated cultures treated with 5 µg/ml, 10 µg/ml and 20 µg/ml of ZOL compared with PHA-stimulated cultures (P<0.05 and P<0.02 and P<0.04, respectively). CONCLUSION: Expression of NK cell-related activating receptors decreased in BC patients. ZOL can improve the expression of NK activating receptors.

Overexpression of Regulatory T Cell-Related Markers (FOXP3, CTLA-4 and GITR) by Peripheral Blood Mononuclear Cells from Patients with Breast Cancer

Background: Regulatory T (Treg) cells are immunosuppressor lymphocytes that play a critical role in the establishment and progression of cancers. A number of markers, especially FOXP3, CTLA-4 and GITR influence the function of Treg cells. This investigation aimed to evaluate the expression of a number of important Treg cell-related markers by peripheral blood mononuclear cells (PBMCs) from newly-diagnosed women with breast cancer. Methods: The fresh PBMCs were obtained from 20 women with breast cancer and 20 healthy individuals. The PBMCs from both groups were cultured for 32 hours in the presence or absence of PHA (10 µg/ml). After total RNA extraction from cultured PBMCs, the expression of the FOXP3, CTLA-4 and GITR transcripts was assessed using real time-PCR. Results: The mRNA expression of FOXP3, CTLA-4 and GITR in unstimulated PBMCs from patients with breast cancer were significantly higher than healthy control group (P<0.05, P<0.03 and P<0.04, respectively). Similarly, the expression of FOXP3, CTLA-4 and GITR transcripts in PHA-stimulated PBMCs from patients with breast cancer were significantly increased in comparison with healthy individuals (P<0.01, P<0.005 and P<0.01, respectively). Conclusion: The increased expression of FOXP3, CTLA-4 and GITR represent higher activity of Treg cells in patients with breast cancer that may play an important role in the tumor establishment and development.

Imbalanced Expression of Th2 and Treg Cell-related Parameters in Peripheral Blood Mononuclear Cells in Patients with Allergic Asthma.

BACKGROUND: The imbalance between Th2 and Treg cells plays fundamental role in the pathogenesis of allergic asthma. The current study aimed at assessing the expression of some Th2 and Treg cell-related parameters in patients with allergic asthma. MATERIAL AND METHODS: The serum and peripheral blood mononuclear cell (PBMC) samples were collected from 30 patients with asthma and 36 healthy subjects. The serum levels of transforming growth factor (TGF)-ß, interleukin (IL)-4, as well as the expression levels of GATA3 and FOXP3 genes in PBMCs were determined by the enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR), respectively. The PBMCs were cultured for 48 hours with/without phytohemagglutinin (PHA) stimulation. The TGF-ß and IL-4 levels in supernatants were also determined. RESULTS: The serum levels of IL-4, the expression level of GATA3, and GATA3/FOXP3 ratio in patients with asthma were significantly higher than healthy subjects (P <0.002, P <0.001, and P <0.004, respectively). The FOXP3 expression did no differ between the two groups. The serum level of TGF-ß as well as its secretion profile in non-stimulated and stimulated PBMCs isolated from patients with asthma were significantly higher than those of the controls (P <0.03, P <0.001, and P <0.001, respectively). The serum TGF-ß levels in severe asthma were significantly higher than moderate asthma; whereas the TGF-ß secretion by PHA-stimulated PBMCs isolated from moderate asthma was higher than that of severe pattern of the disease (P <0.001 and P <0.05, respectively). The GTAT3/FOXP3 expression ratio in moderate asthma was significantly higher than severe form (P <0.04). CONCLUSION: The results confirmed a Th2 cell-biased pattern and possible contribution of TGF-ß in allergic asthma. TGF-ß may have different expression patterns in moderate and severe asthma and the two forms of the disease may have differences in some main immunological parameters.