Low opioid and opioid-free anesthesia - a review of current data

Introduction: Opioids are one of the most frequently used drugs during anesthesia. Due to the side effects anesthesiologists try to limit their number during anesthesia. They use low-opioid and opioid-free anesthesia.  Purpose: The purpose of this work is to present the current state of knowledge and recent reports on low-opioid and non-opioid anesthesia and their use.  Materials and Methods: The search was conducted using PubMed and GoogleScholar databases. Articles were searched in English using the following keywords: "low-opioid anesthesia," "non-opioid anesthesia," "OFA," "LOA"  Key words: "low-opioid anesthesia", "non-opioid anesthesia", "OFA", "LOA", "opioids".  Conclusion: low-opioid anesthesia techniques are being used more and more frequently and reduce the incidence of opioid side effects: respiratory depression, postoperative nausea and vomiting. This helps ensure greater patient safety and shortens the postoperative recovery period.

Molekularne terapie celowane w niedrobnokomórkowym raku płuca

Terapie celowane działają w sposób wybiórczy na białka sygnałowe komórek nowotworowych, powodując upośledzenie ich funkcji życiowych. W niedrobnokomórkowym raku płuca (NDRP) zastosowanie znalazły inhibitory kinaz tyrozynowych związanych z receptorem dla naskórkowego czynnika wzrostu (EGFR): erlotynib i gefitynib. Leki te są stosowane w zaawansowanym raku płuca jako terapia drugiego lub trzeciego rzutu po niepowodzeniu pierwszorzutowej chemioterapii. Cetuximab jest przeciwciałem monoklonalnym skierowanym przeciwko zewnątrzkomórkowej domenie EGFR. Natomiast bewacyzumab jest przeciwciałem blokującym działanie czynnika wzrostu śródbłonka naczyń (VEGF), powodując upośledzenie ukrwienia tkanki nowotworowej. Przeciwciała mogą być stosowane jako uzupełnienie chemioterapii oraz po jej zakończeniu. Mediana czasu życia chorych na zaawansowaną postać NDRP w wyniku stosowania bewacyzumabu wyniosła po raz pierwszy w historii leczenia tego nowotworu ponad 12 miesięcy. Istnieją duże różnice w skuteczności omawianych leków w zależności od genetycznych właściwości komórek nowotworowych. Obecnie najważniejszymi badaniami molekularnymi użytecznymi w kwalifikacji chorych do terapii celowanych są: badanie immunohistochemiczne w celu wykrycia ekspresji EGFR, fluorescencyjna hybrydyzacja in situ, za pomocą której można wykryć amplifikację genu dla EGFR, oraz metody genetyczne zmierzające do określenia występowania mutacji EGFR i K-Ras

TP53 polymorphism in plasma cell myeloma

Introduction. Significant and accessible predictive factors for bortezomib treatment in plasma cell myeloma (PCM) are still lacking. TP53 codon 72 polymorphism (P72R) results in proline (P) or arginine (R) at 72 amino acid position, which causes synthesis of proteins with distinct functions. The aims of our study were to: 1) analyze whether this polymorphism is associated with an increased risk of PCM; 2) study whether the P72R polymorphism affects overall survival (OS) among PCM patients; 3) assess the possible association of the P72R polymorphism with sensitivity to bortezomib in cell cultures derived from PCM patients. Material and methods. Genomic DNA from newly diagnosed 59 patients (without IgVH gene rearrangements and TP53 deletions) and 50 healthy blood donors were analyzed by RFLP-PCR to identify TP53 polymorphism. Chromosomal aberrations were detected by use of cIg-FISH. The lymphocyte cell cultures from a subgroup of 40 PCM patients were treated with bortezomib (1, 2 and 4 nM). Results. The P allele of the P72R polymorphism was more common than the R allele in PMC patients compared to controls (39% vs. 24%), and the difference was significant (p = 0.02). The PP and PR genotypes (in combina­tion) were more frequent among cases than in controls (65% vs. 42%, OR = 2.32, p = 0.04). At the cell culture level and 2 nM bortezomib concentration the PP genotype was associated with higher necrosis rates (10.5%) compared to the PR genotype (5.7%, p = 0.006) or the RR genotype (6.3%, p = 0.02); however, no effect of genotypes was observed at bortezomib concentrations of 1 and 4 nM. The shortest OS (12 months) was observed in patients with the PP genotype compared to patients with the PR or RR genotypes (20 months) (p = 0.04). Conclusions. The results suggest that P72R polymorphisms may be associated with an increased PCM risk and may affect OS of PCM patients. However, we saw no consistent results of the polymorphism effect on apoptosis and necrosis in cell cultures derived from PCM patients. Further studies are need in this regard

The Role of Cluster C19MC in Pre-Eclampsia Development

Pre-eclampsia is a placenta-related complication occurring in 2–10% of all pregnancies. miRNAs are a group of non-coding RNAs regulating gene expression. There is evidence that C19MC miRNAs are involved in the development of the placenta. Deregulation of chromosome 19 microRNA cluster (C19MC) miRNAs expression leads to impaired cell differentiation, abnormal trophoblast invasion and pathological angiogenesis, which can lead to the development of pre-eclampsia. Information was obtained through a review of articles available in PubMed Medline. Articles on the role of the C19MC miRNA in the development of pre-eclampsia published in 2009–2022 were analyzed. This review article summarizes the current data on the role of the C19MC miRNA in the development of pre-eclampsia. They indicate a significant increase in the expression of most C19MC miRNAs in placental tissue and a high level of circulating fractions in serum and plasma, both in the first and/or third trimester in women with PE. Only for miR-525-5p, low levels of plasma expression were noted in the first trimester, and in the placenta in the third trimester. The search for molecular factors indicating the development of pre-eclampsia before the onset of clinical symptoms seems to be a promising diagnostic route. Identifying women at risk of developing pre-eclampsia at the pre-symptomatic stage would avoid serious complications in both mothers and fetuses. We believe that miRNAs belonging to cluster C19MC could be promising biomarkers of pre-eclampsia development

Significance of Polymorphisms and Expression of Enzyme-Encoding Genes Related to Glutathione in Hematopoietic Cancers and Solid Tumors

Antioxidant compounds such as glutathione and its enzymes have become the focus of attention of medical sciences. Glutathione, a specific tripeptide, is involved in many intercellular processes. The glutathione concentration is determined by the number of GAG repeats in gamma-glutamylcysteine synthetase. GAG polymorphisms are associated with an increased risk of schizophrenia, berylliosis, diabetes, lung cancer, and nasopharyngeal tumors. Cancer cells with high glutathione concentration are resistant to chemotherapy treatment. The oxidized form of glutathione is formed by glutathione peroxidases (GPXs). The changes in activity of GPX1, GPX2, and GPX3 isoforms may be associated with the development of cancers, for example, prostate cancer or even colon cancer. Detoxification of glutathione conjugates is possible due to activity of glutathione S-transferases (GSTs). Polymorphisms in GSTM1, GSTP1, and GSTO1 enzymes increase the risk of developing breast cancer and hepatocellular carcinoma. Gamma-glutamyl transpeptidases (GGTs) are responsible for glutathione degradation. Increased activity of GGT correlates with adverse prognosis in patients with breast cancer. Studies on genes encoding glutathione enzymes are continued in order to determine the correlation between DNA polymorphisms in cancer patients

Badanie wewnątrztandemowej duplikacji genu chorych z ostrą białaczką szpikową

Acute myeloid leukemia (AML) is a heterogeneous hematologic disease. A FLT3-internal tandem duplication (FLT3-ITD) mutation imparts a particularly poor prognosis. It is found approximately in 25% of patients with AML (in all subtypes according to FAB classification). Mutations of FLT3 are the most common abnormalities in AML patients with normal karyotypes.To assess the internal tandem mutation in FLT3 gene we used polymerase chain reaction (PCR) to screen 15 AML patients. FLT3-ITD mutation was detected in 4 of 15 patients with AML.Ostra białaczka szpikowa (OBS) jest zróżnicowaną chorobą hematologiczną. Wewnątrztandemowa duplikacja genu FLT3 (FLT3-ITD) wpływa niekorzystnie na rokowanie i jest wykrywana u około 25% chorych na OBS (we wszystkich podtypach według klasyfikacji FAB). Mutacje genu FLT3 występują najczęściej u chorych na OBS z prawidłowym kariotypem. W celu wykrycia mutacji FlT3-ITD wykorzystano reakcję łańcuchowej polimerazy (PCR). Badanie wykonano u 15 chorych na OBS, u 4 chorych wykryto mutację FlT3-ITD

<i>WT1</i> Gene Mutations, rs16754 Variant, and <i>WT1</i> Overexpression as Prognostic Factors in Acute Myeloid Leukemia Patients

(1) Background: The aim of our study was the complex assessment of WT1 variants and their expression in relation to chromosomal changes and molecular prognostic markers in acute myeloid leukemia (AML). It is the first multidimensional study in Polish AML patients; (2) Methods: Bone marrow aspirates of 90 AML patients were used for cell cultures (banding techniques and fluorescence in situ hybridization), and to isolate DNA (WT1 genotyping, array comparative genomic hybridization), and RNA (WT1 expression). Peripheral blood samples from 100 healthy blood donors were used to analyze WT1 rs16754; (3) Results: Allele frequency and distribution of WT1 variant rs16754 (A;G) did not differ significantly among AML patients and controls. Higher expression of WT1 gene was observed in AA genotype (of rs16754) in comparison with GA or GG genotypes—10,556.7 vs. 25,836.5 copies (p = 0.01), respectively. WT1 mutations were more frequent in AML patients under 65 years of age (p NPM1 or CEBPA mutations decreased the risk of WT1 mutation presence, odds ratio (OR) = 0.11, 95% CI 0.02–0.46, p = 0.002 or OR = 0.05, 95% CI 0.006–0.46, p = 0.002, respectively. We observed significantly higher WT1 expression in AML CD34+ vs. CD34−, −20,985 vs. 8304 (p = 0.039), respectively. The difference in WT1 expression between patients with normal and abnormal karyotype was statistically insignificant; (4) Conclusions: WT1 gene expression and its rs16754 variant at diagnosis did not affect AML outcome. WT1 mutation may affect RFS in AML

Analysis of Circulating C19MC MicroRNA as an Early Marker of Hypertension and Preeclampsia in Pregnant Patients: A Systematic Review

Preeclampsia and hypertension complicate several pregnancies. Identifying women at risk of developing these conditions is essential to establish potential treatment modalities. Biomarkers such as C19MC microRNA in pregnant patients wopuld assist in defining pregnancy surveillance and implementing interventions. This study sought to analyze circulating C19MC microRNA as an early marker of hypertension and preeclampsia in pregnant patients. A systematic review was undertaken using the following registers: disease registries, pregnancy registries, and pregnancy exposure registries, and the following databases: PubMed, CINAHL, Web of Science, Scopus, and EMBASE. The risk of bias was assessed using the Cochrane technique. From the 45 publications retrieved from the registers and databases, only 21 were included in the review after the removal of duplicates, screening, and eligibility evaluation. All 210 publications had a low risk of bias and illuminated the potential use of circulating C19MC microRNA as an early marker of hypertension and preeclampsia in pregnant patients. Therefore, it was concluded that C19MC microRNA can be used as an early marker of gestational preeclampsia and hypertension