ABSTRACT
The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60-35.40) vs. 22.95 mg/dL (17.60-33.30), p = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678-1.189; p = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG-33.8%, GA-50.2%, and AA-16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure (p = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases.
Subject(s)
Cardiovascular Diseases , Fucosyltransferases , Galactoside 2-alpha-L-fucosyltransferase , Kidney Transplantation , Polymorphism, Single Nucleotide , Humans , Fucosyltransferases/genetics , Kidney Transplantation/adverse effects , Male , Female , Cardiovascular Diseases/genetics , Cardiovascular Diseases/etiology , Middle Aged , Adult , Risk Factors , Genetic Predisposition to Disease , Genotype , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Cyclosporine/therapeutic use , Cyclosporine/adverse effects , Tacrolimus/adverse effects , Tacrolimus/therapeutic useABSTRACT
INTRODUCTION: Pigmentary changes can be bothersome and affect one's well-being. Laser therapy has been shown to effectively treat such skin discolouration. We aimed to assess the utility of a 755 nm alexandrite laser in pigmented lesions removal. MATERIALS AND METHODS: A total of 109 patients aged 44.17 ± 8.2 years were enrolled and underwent laser treatment of facial skin hyperpigmentation. The efficacy was analysed on the basis of photographic diagnosis using the VISIA Complexion Analysis System. The following measures were assessed: (1) score; (2) feature count; (3) comparison figure. RESULTS: A single laser treatment significantly improved the size and area of the lesion and decreased the number of lesion features. Parallelly, the overall skin condition significantly improved (p < 0.05). We found a statistical tendency of a higher feature count baseline, thus its change in men (p = 0.05 and 0.07, respectively), but failed to find any statistically significant associations (p > 0.05) between tested measures and skin phototypes and hyperpigmentation types. Age was also not correlated with the laser efficacy (p > 0.05). CONCLUSIONS: The use of the 755 nm laser is effective in reducing pigmented lesions.
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BACKGROUND: to analyse the effect of haematological indices on the occurrence of Delayed Graft Function (DGF) in patients undergoing kidney transplantation and on the function of the transplanted kidney on the 7th postoperative day. METHODS: 365 recipients who underwent kidney transplantation from a donor with known brain death between 2010 and 2017 were included in this retrospective study. Information from patient medical records, donor medical records, and donation and transplantation protocols was used for analysis. Statistica 13 was used for statistical analysis. RESULTS: In the study group, DGF occurred in 144 recipients (39.45%), and Non-Graft Function (NGF) occurred in 12 recipients (3.29%). Recipients who developed DGF had a significantly higher Neutrophil/Monocyte Ratio (NMR) before renal transplantation (p = 0.048), a lower NMR value on postoperative day 1 (p < 0.001), and a difference between the values on day 1 and before surgery (p < 0.001). In addition, they had a significantly lower Lymphocyte/Monocyte Ratio (LMR) on postoperative day 1 LMR 1 (p < 0.001). It was shown that the value of the indices based on the ROC curve-NMR1 > 29.29, NMR1-0 > 22.71, and LMR1 > 1.74 (respectively: AUC = 0.624; 95% CI 0.566-0.682; and p < 0.001/AUC = 0.622; 95% CI 0.563-0.680; and p < 0.001/AUC = 0.610; 95% CI 0.550-0.670; and p < 0.001)-can be used to identify recipients with a significant probability of DGF. CONCLUSIONS: the NMR and LMR parameters on the first postoperative day and the difference between the NMR values on the first post-transplant day and the first pre-transplant day are predictive factors associated with the risk of DGF.
ABSTRACT
In March 2020, the World Health Organization (WHO) announced a global pandemic of coronavirus disease 2019 (COVID-19) that presented mainly as an acute infection of the lower respiratory tract (pneumonia), with multiple long-term consequences, including lung fibrosis. The aim of this study was to evaluate the influence of potassium canrenoate on inflammatory markers in the treatment of COVID-19 pneumonia. A randomized clinical trial (RCT) of intravenous potassium canrenoate vs. placebo was performed between December 2020 and November 2021. This study is a secondary analysis of that RCT. In the final analysis, a total of 49 hospitalized patients were included (24 allocated to the potassium canrenoate group and 25 to the placebo group). Patients were assessed by serum testing and blood cell cytometry on day 1 and day 7 of the intervention. Age, sex, and body mass index were not significantly different between the placebo group and intervention group. Although there was a significantly higher rate of ischemic heart disease in the placebo group, rates of other preexisting comorbidities were not significantly different. There were no significant differences in the inflammatory parameters between the potassium canrenoate and placebo groups on day 1 and day 7. However, the intragroup comparisons using Wilcoxon's test showed significant differences between day 1 and day 7. The CD3% for potassium canrenoate increased significantly between day 1 and day 7 (12.85 ± 9.46; 11.55 vs. 20.50 ± 14.40; 17.80; p = 0.022), while the change in the placebo group was not significant (15.66 ± 11.39; 12.65 vs. 21.16 ± 15.37; 16.40; p = 0.181). The IL-1ß total count [%] increased over time for both potassium canrenoate (0.68 ± 0.58; 0.45 vs. 1.27 ± 0.83; 1.20; p = 0.004) and placebo (0.61 ± 0.59; 0.40 vs. 1.16 ± 0.91; 1.00; p = 0.016). The TNF-α total count (%) decreased significantly between day 1 and day 7 for potassium canrenoate (0.54 ± 0.45; 0.40 vs. 0.25 ± 0.23; 0.10; p = 0.031), but not for placebo (0.53 ± 0.47; 0.35 vs. 0.26 ± 0.31; 0.20; p = 0.056). Interleukin-6 (pg/mL) showed a significant decrease between day 1 and day 7 for potassium canrenoate (64.97 ± 72.52; 41.00 vs. 24.20 ± 69.38; 5.30; p = 0.006), but not the placebo group. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19-induced pneumonia may be associated with significant changes in certain inflammatory markers (interleukin-6, CD3%, TNF-α), potentially related to pulmonary fibrosis. Although some positive trends were observed in the potassium canrenoate group, none of these observations reached statistical significance. Any possible benefits from the use of potassium canrenoate as an anti-inflammatory or antifibrotic drug in COVID-19 patients require further investigation.
Subject(s)
COVID-19 , Humans , Mineralocorticoid Receptor Antagonists/therapeutic use , Canrenoic Acid/therapeutic use , SARS-CoV-2 , Interleukin-6 , Tumor Necrosis Factor-alpha , Inflammation/drug therapy , Fibrosis , Treatment OutcomeABSTRACT
Post-transplant diabetes mellitus (PTDM) is a common complication that occurs in kidney transplant patients, increasing the risk of infection, cardiovascular disease and loss of graft function. Currently, factors that increase the risk of this complication are being sought, among them polymorphisms in genes that regulate carbohydrate metabolism and influence pancreatic ß-cell function. The aim of this study was to evaluate the association of selected polymorphisms of genes affecting carbohydrate metabolism, such as CDKAL1 rs10946398, GCK rs1799884, GCKR rs780094 and DGKB/TMEM195 rs2191349, with the development of post-transplant diabetes in kidney transplant patients. This study included 201 Caucasian patients after kidney transplantation treated with tacrolimus. An association was observed between the CDKAL1 rs10946398 gene polymorphism and PTDM. Among patients with PTDM, there was an increased prevalence of the CC genotype in the PTDM group compared to the group without PTDM. The chance of PTDM in those with the CC genotype was 2.60 times higher compared to those with the AC + AA genotypes (CC vs. AC + AA OR (95% CI): 2.60 (1.02-6.61), p = 0.040). Multivariate logistic regression analysis showed that advanced age and the CC genotype (rare homozygote) of CDKAL1 rs10946398 were risk factors for the development of PTDM at 1 year after transplantation. There was no statistically significant association between GCK rs1799884, GCKR rs780094 or DGKB/TMEM195 rs2191349 polymorphisms and the development of post-transplant diabetes mellitus in kidney transplant patients. The results of this study suggest that the CDKAL1 rs10946398 CC genotype is associated with the increased risk of PTDM development in patients after kidney graft transplantation treated with tacrolimus.
Subject(s)
Diabetes Mellitus , Tacrolimus , Humans , Tacrolimus/adverse effects , Kidney , Diabetes Mellitus/drug therapy , Diabetes Mellitus/genetics , Polymorphism, Genetic , Allografts , tRNA MethyltransferasesABSTRACT
The risk of losing a transplanted organ is high, and non-invasive markers to warn of this phenomenon are still being sought. We investigated the impact of post-transplant microchimerism on the function of the transplanted kidney. The study included 100 kidney transplant recipients, mostly women. All transplanted organs were from opposite-sex deceased donors. Microchimerism was assessed using multiplex PCR. Male DNA was detected in all urine samples from female recipients and in 13/56 blood samples from female kidney recipients. Female DNA was found in 31/44 urine samples from male recipients, but in none of the blood samples. Microchimerism in the urine of female recipients correlated positively with blood urea (Rs = 0.45; p = 5.84 × 10-4) and K+ ions (Rs = 0.29; p = 0.03), while microchimerism in the blood of female recipients also correlated positively with blood urea (Rs = 0. 28; p = 0.04), cystatin C (Rs = 0.31; p = 0.02) and the number of incompatible HLA alleles (Rs = 0.42; p = 0.01). A history of DGF was associated with higher urinary donor DNA concentrations in female recipients.: Post-transplant microchimerism may serve as a potential marker of chronic kidney rejection.
Subject(s)
Kidney Transplantation , Humans , Male , Female , Kidney Transplantation/adverse effects , Chimerism , Transplantation Chimera , Graft Rejection/genetics , DNA/genetics , Tissue Donors , UreaABSTRACT
As pharmacology and science progress, we discover new generations of medicines. This relationship is a response to the increasing demand for medicaments and is powered by progress in medicine and research about the respective entities. However, we have questions about the efficiency of pharmacotherapy in individual groups of patients. The effectiveness of therapy is controlled by many variables, such as genetic predisposition, age, sex and diet. Therefore, we must also pay attention to the microbiota, which fulfill a lot of functions in the human body. Drugs used in psychiatry, gastroenterology, diabetology and other fields of medicine have been demonstrated to possess much potential to change the composition and probably the function of the intestinal microbiota, which consequently creates long-term risks of developing chronic diseases. The article describes the amazing interactions between gut microbes and drugs currently used in healthcare.
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INTRODUCTION: Due to the SARS-CoV-2 coronavirus pandemic, the wearing of masks has become a common phenomenon. Most of the undesirable effects of using a protective face covering are usually related to the prolonged time of its wearing, and the adverse consequences of face coverings should be considered two-fold. The aim of the study was to evaluate the rate of contamination of the three types of face coverings (surgical, N95, and FFP2 masks) with the microorganism-aerobic bacteria, yeasts, and molds-after the 3 h exposure time. The study aimed to investigate the effects of wearing FFP2 masks (KN95) on respiratory function and the acid-base balance of the human body. RESULTS: The presence of S. aureus was confirmed in both nasal carriers and non-carriers which may demonstrate the cross-contamination and spread of this bacterium via hands. S. aureus was found on external and internal surfaces of face masks of each type, and therefore could also be transmitted via hands from external sources. The 3 h exposure time is not sufficient for Gram-negative rods and mold contamination. Moreover, there were no significant differences in most of the parameters studied between the first and second examinations, both in spirometry and capillary blood gas analysis (p > 0.05).
Subject(s)
COVID-19 , Staphylococcal Infections , Humans , COVID-19/epidemiology , SARS-CoV-2 , Staphylococcus aureus , Pandemics , Acid-Base Equilibrium , MasksABSTRACT
Purpose: Chemoembolization of liver lesions, metastatic from colorectal cancer (CRC), with irinotecan-loaded microspheres shows less efficacy if applied after previous systemic chemotherapy. This is because cancer cells acquire resistance to previously used chemotherapeutic agents, e.g., irinotecan or perhaps via, e.g., modulations of EGFR receptors after use of anti-EGFR antibodies. Objective: To evaluate the effects of prior treatment with anti-EGFR (cetuximab) antibodies on the efficacy of chemoembolization, with irinotecan-loaded microspheres, of liver lesions metastatic from CRC. Patients and methods: The study included 50 patients (27 female, 23 male) with inoperable liver metastases in the course of CRC who underwent a total of 192 chemoembolization procedures with microspheres loaded with 100 mg of irinotecan. Chemoembolization of the right or left liver lobes was performed alternately at three-week intervals. Patients were divided into two groups: group A (n = 26): patients who had previously received anti-EGFR (cetuximab) antibodies; and group B (n = 24): patients who had never received anti-EGFR antibodies. Response to treatment was assessed according to mRECIST criteria. Overall survival time (OS) was calculated using the Kaplan−Meier method. Evaluation of adverse effects was performed according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (Version 5.0). Results: Analysis did not show a statistically significant difference in radiological response between the two groups: partial response: 36.2% in group A and 32.9% in group B (p = 0.139); and stable disease: 19.2% in group A and 21.7% in group B (p = 0.224). Post-treatment progression was comparable at 46.2% in group A and 41.6% in group B (p = 0.343). There was a significant difference in OS (p = 0.043 log-rank test), however, prior treatment with cetuximab showed no significant effect on OS in a Cox proportional hazards regression model HR 1.906 (0.977−3.716), p = 0.058. Mean OS was 15.2 months (95% confidence interval (Cl): 6 to 23 months) in group A and 13.1 months (95% Cl: 7 to 22 months) in group B. In both groups, there was a negative correlation between carcinoembryonic antigen (CEA) levels below 10 mg/mL before surgery and OS (hazard ratio (HR) 0.83 (0.47−8.43), p = 0.005 in group A and HR 1.02 (0.56−7.39), p = 0.003 in group B). There was no significant difference in the number of prominent complications between group A (7 complications) and group B (6 complications), p = 0.663. Conclusions: Previous therapy with anti-EGFR antibodies before treatment with irinotecan chemoembolization of liver metastatic lesions did not have a significant effect on radiological response to treatment or post-treatment progression. However, higher baseline levels of CEA (>10 ng/mL) were correlated with worse OS (p = 0.039).
ABSTRACT
Aesthetic medicine is a dynamically developing field of medicine. It has an impact not only on the improvement of the external appearance, but also on health and quality of life. Currently, vascular changes affect many patients and significantly diminish the condition of the skin. The development of modern laser therapy has contributed to the successful management of multiple skin conditions, among them vascular lesions. The aim of our study was to show the efficacy of repetitive 532 nm laser therapy in reducing vascular skin lesions located on the facial area. Observations were possible due to the implementation of System of Skin Analysis. We retrospectively analyzed the records of 120 patients (100 women and 20 men) using "VISIA" Skin Analysis System after 532 nm laser therapy. Treatment with the use of the 532 nm vascular laser turned out to be effective in reducing vascular changes in both women and men. The skin phototypes did not significantly affect the therapy efficacy. Neither the age of patients nor number of laser sessions affect therapy efficacy. 532 nm laser therapy is effective in reducing vascular skin lesions located in the face area.
Subject(s)
Quality of Life , Skin Diseases , Male , Humans , Female , Treatment Outcome , Retrospective Studies , Skin , LasersABSTRACT
Fournier gangrene represents a urologic emergency. It is a rapidly progressing necrotizing fasciitis that comprises the perineal, perianal, and genital regions and has a high mortality rate. Diagnosis is usually made clinically, but radiological diagnostics, such as ultrasound (US), computed tomography (CT), or magnetic resonance imaging (MRI), can determine the extent of the disease in relation to pelvic structures. Early and accurate diagnosis precipitates the initiation of the effective treatment and, thus, affects the outcome of the therapy. The article reports an illustrative case study of a patient with Fournier gangrene, secondary to a perianal fistula and perianal abscess with a massive accumulation of fluid around the anus and testicles, requiring unilateral orchidectomy. Rapid radiological diagnosis via MRI enabled precise assessment of the degree of the disease, early surgical intervention, and a successful outcome.
ABSTRACT
Purpose: Esthetic medicine is a rapidly developing field of medicine that is not only beneficial in terms of external appearance, but also significantly improves overall quality of life. Currently, pigmented and vascular skin lesions are more prevalent due to multiple environmental factors and are a characteristic manifestation of skin aging. The development of modern laser therapy has contributed to the successful management of multiple skin conditions. The aim of our study was to show the effect of concomitant reduction of both vascular and hyperpigmented skin lesions located on the facial area after repetitive 532 nm laser therapy and to emphasize that the detection of such observation was possible due to the implementation of System of Skin Analysis and Assessment. Patients and Methods: We retrospectively analyzed 100 patients' records with "VISIA" Skin Analysis System after 532nm laser therapy. Results: Laser therapy significantly decreased VISIA scores for all tested lesions, ie, macules, pigmented and vascular lesions (p<0.0001 for all). The efficacy of laser treatment was not significantly different regarding skin phototype (p>0.05) and did not correlate with age of participants (p>0.05). The more laser sessions were performed, the higher improvement in vascular lesion VISIA scores was observed (r=0.26, p=0.0097). Conclusion: 532 nm laser therapy is effective regarding vascular and hyperpigmented skin lesions located on the facial area. The System of Skin Analysis and Assessment is a good tool to test the treatment efficacy during regular follow-up procedure.
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The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2), has triggered an enormous scientific response. Many studies have focused on understanding the entry of the SARS-CoV-2 virus into the host cell. The angiotensin-converting enzyme-2 (ACE2) is recognized as the host receptor used by SARS-CoV-2 to enter its target cells. Recent studies suggest that ACE2 gene polymorphisms might be candidates for genetic susceptibility to SARS-CoV-2 infection. The aim of this study is to evaluate the influence of ACE2 polymorphisms on COVID-19 disease risk and severity. In our study, we confirmed that there is a statistically significant increased risk of a more severe disease course of SARS-CoV-2 infection associated with the need for hospitalization in intensive care for patients with specific polymorphisms of the ACE2 gene. The most significant correlation was found for variant ACE2 rs2285666 (AA allele, OR = 2.12, p = 0.0189) and ACE2 rs2074192 (TT allele, OR = 2.05, p = 0.0016), and for ACE2 rs4646174 (GG allele, OR = 1.93, p = 0.0016), ACE2 rs4646156 (TT allele OR = 1.71, p = 0.008) and ACE2 rs2158083 (TT allele OR = 1.84, p = 0.0025). In conclusion, our findings identify that certain ACE2 polymorphisms impact the severity of COVID-19 disease independently of other well-known risk factors.
Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19 , Angiotensins/genetics , COVID-19/epidemiology , COVID-19/genetics , Genetic Predisposition to Disease , Humans , Pandemics , Peptidyl-Dipeptidase A/genetics , SARS-CoV-2/geneticsABSTRACT
Limited social contacts, lack of professional activities, economic insecurity, and a sense of threat, as well as boredom during the COVID-19 pandemic, contributed to tension and stress. All of these increase the risk of an inappropriate diet. The aim of this cross-sectional study was to assess the impact of the COVID-19 pandemic on the mood and nutrition of patients undergoing bariatric surgery. A group of 312 patients (both before and after bariatric surgery) completed a questionnaire about their diet and mood during COVID-19 lockdown. About 70% of all respondents reacted to the epidemiological situation: irritability, anxiety about their own health, and eating without being hungry. A total of 74% of all of the subjects snacked between meals (especially sweets). The respondents who believed that obesity and its complications had a negative impact on the prognosis of the coronavirus infection had a statistically significant higher prevalence of health anxiety, feeling that important life issues were out of control, irritability, need for psychological support, and need for dietary consultation. Patients after bariatric surgery had e.g., a statistically significant lower incidence of feeling hungry, eating after meals, and eating fatty foods. The COVID-19 pandemic has been shown to negatively affect the mood and diet of bariatric patients, which may affect their health status and worsen the prognosis of COVID-19.
Subject(s)
Bariatric Surgery , COVID-19 , Bariatric Surgery/psychology , COVID-19/epidemiology , Communicable Disease Control , Cross-Sectional Studies , Diet , Humans , PandemicsABSTRACT
BACKGROUND: In Poland, 95% of organs for transplantation come from donation after brain death (DBD). In 2010, Poland officially joined the European countries in which donation after circulatory death is accepted by law. Currently, the Pomeranian Medical University Transplant Center is the only active location for uncontrolled donation after circulatory death (uDCD) in Poland. To estimate the results of uDCD kidney transplantation with a classical approach to organ recovery, we analyzed data from an early phase of uDCD program. METHODS: Prospective observation of uDCD kidney allografts (group 1; n = 8) compared with DBD kidney allografts (group 2; n = 30). The organ recovery protocol was set up on rapid abdominal access without regional perfusion before procurement. RESULTS: The organs recovered from uDCD during a 24-month period increased the volume of kidneys transplanted at the center by 9.2%. Delayed graft function was diagnosed in 100% vs 46% of allografts (P = .03), respectively. Nevertheless, early posttransplant follow-up did not reveal any graft loss or recipient death cases in the DCD group. After 12 months of follow-up, the mean glomerular filtration rate was 44.5 vs 57.9 mL/min (P < .02), respectively. Crucial factors for acceptable results of uDCD are strict pretransplant assessment of recovered organs and efficient coordination of the transplant team. CONCLUSIONS: Conservative recovery protocol in uDCD under strict prerequisites is feasible to consider in the organ procurement pathway. Preliminary results provide space for an increase in the organ donor pool.
Subject(s)
Graft Survival , Tissue and Organ Procurement , Algorithms , Brain Death , Death , Humans , Prospective Studies , Retrospective Studies , Tissue DonorsABSTRACT
In December 2019 the SARS-CoV-2 virus appeared in the world, mainly presenting as an acute infection of the lower respiratory tract, namely pneumonia. Nearly 10% of all patients show significant pulmonary fibrotic changes after the infection. The aim of this study was to evaluate the effectiveness and safety of potassium canrenoate in the treatment of COVID-19-associated pneumonia and pulmonary fibrosis. We performed a randomized clinical trial (RCT) of potassium canrenoate vs placebo. A total of 55 patients were randomized and 49 were included in the final analysis (24 allocated to the intervention group and 25 allocated to the control group). Patients were assessed by physical examination, lung ultrasound, CT imaging and blood samples that underwent biochemical analysis. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19 induced pneumonia was not associated with shorter mechanical ventilation time, shorter passive oxygenation, shorter length of hospitalization or less fibrotic changes on CT imaging. The overall mortality rate was not significantly different between the two groups. Adverse events recorded in this study were not significantly increased by the administration of potassium canrenoate. The negative outcome of the study may be associated with the relatively small number of patients included. Any possible benefits from the use of potassium canrenoate as an antifibrotic drug in COVID-19 patients require further investigation.
ABSTRACT
Organ transplant is often the treatment of choice as it extends and improves patient life. Immunosuppressive treatment, which prevents acute rejection of the organ, is used in transplant patients to prevent the loss of transplant. The aim of the study was to determine the impact of the CTLA4 (+49A>G, rs231775) and the TGF-ß1 (-800G>A, rs1800468) polymorphisms on the therapeutic effect of immunosuppressive drugs (cyclosporine-CsA, tacrolimus-TAC) and the risk of acute rejection in renal transplant patients. The analysis of the CTLA4 +49A>G and the TGF-ß1 -800G>A polymorphisms was carried out in 392 patients after kidney transplant using real-time PCR. The CTLA4 +49A>G polymorphism did not affect CsA or TAC dose, ratio of drug concentration to dose (C/D), and blood concentrations. As for the TGF-ß1 -800G>A polymorphism, patients with the GA genotype required lower TAC doses compared to the GG genotype (TAC 12 h: 3.63 mg vs 5.3 mg, TAC 24 h: 2.38 mg vs 3.29 mg). Comparing the C/D ratio in both groups (TAC 12 h and TAC 24 h), higher C/D ratio was observed in patients with the GA genotype. These results indicate that patients with the A allele require slightly lower doses of TAC. The results suggest that the TGF-ß1 -800 G>A polymorphism may influence the TAC dose, while the +49A>G polymorphism of the CTLA4 gene does not correlate with the dose of CsA or TAC. The analysis of the biochemical parameters of the renal profile showed no impact of the CTLA4 and the TGF-ß1 polymorphisms on the risk of organ rejection.
Subject(s)
CTLA-4 Antigen/genetics , Graft Rejection/pathology , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/adverse effects , Transforming Growth Factor beta1/genetics , Adult , Aged , Aged, 80 and over , Calcineurin/administration & dosage , Cyclosporine/administration & dosage , Female , Graft Rejection/drug therapy , Graft Rejection/etiology , Graft Rejection/metabolism , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Tacrolimus/administration & dosage , Treatment Outcome , Young AdultABSTRACT
Ischemia-reperfusion injury (IRI) after renal transplantation is a complex biochemical process. The first component is an ischemic phase during kidney storage. The second is reperfusion, the main source of oxidative stress. This study aimed to analyze the activity of enzymes and concentrations of non-enzymatic compounds involved in the antioxidant defense mechanisms: glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione transferase (GST), thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA), measured in preservation fluid before transplantation of human kidneys (KTx) grafted from brain dead donors. The study group (N = 66) was divided according to the method of kidney storage: Group 1-hypothermic machine perfusion (HMP) in LifePort perfusion pump, n1 = 26, and Group 2-static cold storage (SCS), n2 = 40. The measurements of kidney function parameters, blood count, and adverse events were performed at constant time points during 7-day hospitalization and 3-month follow-up. Kidney perfusate in Group 2 was characterized by significantly more acidic pH (p < 0.0001), higher activity of GPX [U/mgHb] (p < 0.05) and higher concentration of MDA [µmol/L] (p < 0.05). There was a statistically significant improvement of kidney function and specific blood count alterations concerning storage method in repeated measures. There were aggregations of significant correlations (p < 0.05) between kidney function parameters after KTx and oxidative stress markers: diuresis & CAT, Na+ & CAT, K+ & GPX, urea & GR. There were aggregations of significant correlations (p < 0.05) between recipient blood count and oxidative stress markers: CAT & MON, SOD & WBC, SOD & MON. Study groups demonstrated differences concerning the method of kidney storage. A significant role of recipient's gender, gender matching, preservation solution, and perfusate pH was not confirmed, however, basing on analyzed data, the well-established long-term beneficial impact of HMP on the outcome of transplanted kidneys might partially depend on the intensity of IRI ischemic phase and oxidative stress, reflected by the examined biomarkers.
ABSTRACT
Oxidative stress is an imbalance between pro- and antioxidants that adversely influences the organism in various mechanisms and on many levels. Oxidative damage occurring concomitantly in many cellular structures may cause a deterioration of function, including apoptosis and necrosis. The damage leaves a molecular "footprint", which can be detected by specific methodology, using certain oxidative stress biomarkers. There is an intimate relationship between oxidative stress, inflammation, and functional impairment, resulting in various diseases affecting the entire human body. In the current narrative review, we strengthen the connection between oxidative stress mechanisms and their active compounds, emphasizing kidney damage and renal transplantation. An analysis of reactive oxygen species (ROS), antioxidants, products of peroxidation, and finally signaling pathways gives a lot of promising data that potentially will modify cell responses on many levels, including gene expression. Oxidative damage, stress, and ROS are still intensively exploited research subjects. We discuss compounds mentioned earlier as biomarkers of oxidative stress and present their role documented during the last 20 years of research. The following keywords and MeSH terms were used in the search: oxidative stress, kidney, transplantation, ischemia-reperfusion injury, IRI, biomarkers, peroxidation, and treatment.
Subject(s)
Acute Kidney Injury/metabolism , Kidney Transplantation , Kidney/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Reperfusion Injury/metabolism , Acute Kidney Injury/history , Acute Kidney Injury/pathology , Animals , Biomarkers/metabolism , History, 21st Century , Humans , Kidney/pathology , Reperfusion Injury/history , Reperfusion Injury/pathologyABSTRACT
Chemoembolization with irinotecan-loaded microspheres has proven effective in the treatment of unresectable liver metastases in the course of colorectal cancer (CRC). Most researchers recommend slowly administering the embolizate at the level of the lobar arteries, without obtaining visible stasis. However, there are reports of a relationship between postoperative embolizate retention in metastatic lesions and the response to treatment. To retain residual embolizate throughout the entire neoplastic lesion requires a temporary flow stop (stasis) within all supply vessels, which may cause temporary stasis in subsegmental or even segmental vessels. OBJECTIVE: To assess the risk of complications and post-embolization syndrome severity following chemoembolization of CRC metastatic liver lesions with microspheres loaded with Irinotecan, with regard to hepatic-artery branch level of temporary stasis. PATIENTS AND METHODS: The study included 52 patients (29 female, 23 male) with liver metastases from CRC, who underwent 202 chemoembolization treatments (mean: 3.88 per patient) with microspheres loaded with 100 mg irinotecan. Postembolization syndrome (PES) severity and complication occurrence were assessed with regard to the hepatic-artery branch level of temporary stasis. Adverse events were assessed according to Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events. RESULTS: Median survival from the start of chemoembolization was 13 months. From 202 chemoembolization sessions, 15 (7.4%) significant complications were found. The study found a significant relationship between the branch level of temporary stasis and the presence of complications (p < 0.001), with the highest number of complications observed with temporary stasis in segmental vessels. PES was diagnosed after 103 (51%) chemoembolization treatments. A significant association was found between PES severity and the branch level of temporary stasis (p < 0.001). CONCLUSIONS: The branch level of temporary stasis affected the severity of post-embolization syndrome. A significant association was found between the branch level of temporary stasis obtained in chemoembolization procedures and the presence of complications. The apparent lack of change in numbers of complications when stasis was applied at tumor supply vessels or subsegmental arteries may indicate the safe use of temporary stasis in some cases where colorectal cancer metastases are treated. Further research is needed to determine the most effective chemoembolization technique.