Can the pan-immune-inflammation value predict gram negative bloodstream infection-related 30-day mortality in solid organ transplant patients?

BACKGROUND: The recently used pan-immune-inflammation value (PIV) has not been adequately studied as a predictive marker for mortality in immunosuppressed patients. The aim of this study was to evaluate the usefulness of baseline PIV level as a predictor of 30-day mortality in solid organ transplant (SOT) recipients with gram negative bloodstream infections (GN-BSI). METHODS: This retrospective, cross-sectional study was conducted between January 1, 2019, and December 31, 2022, in 1104 SOT recipients. During the study period, 118 GN-BSI were recorded in 113 patients. Clinical, epidemiological, and laboratory data were collected, and mortality rates (30-day and all-cause) were recorded. RESULTS: The 113 recipients had a median age of 50 years [interquartile range (IQR) 37.5-61.5 years] with a male predominance (n = 72, 63.7%). The three most common microorganisms were as follows: 46 isolates (38.9%) of Escherichia coli, 41 (34.7%) of Klebsiella pneumoniae, and 12 (10.2%) of Acinetobacter baumannii. In 44.9% and 35.6% of the isolates, production of extended-spectrum beta-lactamases and carbapenem resistance were detected, respectively. The incidence of carbapenem-resistant GN-BSI was higher in liver recipients than in renal recipients (n = 27, 69.2% vs n = 13, 17.6%, p < 0.001). All-cause and 30-day mortality rates after GN-BSI were 26.5% (n = 30), and 16.8% (n = 19), respectively. In the group with GN-BSI-related 30-day mortality, the median PIV level was significantly lower (327.3, IQR 64.8-795.4 vs. 1049.6, IQR 338.6-2177.1; p = 0.002). The binary logistic regression analysis identified low PIV level [hazard ratio (HR) = 0.93, 95% confidence interval (CI) 0.86-0.99; p = 0.04], and increased age (HR = 1.05, 95% CI 1.01-1.09; p = 0.002) as factors associated with 30-day mortality. The receiver operating characteristic analysis revealed that PIV could determine the GN-BSI-related 30-day mortality with area under curve (AUC): 0.723, 95% CI 0.597-0.848, p = 0.0005. CONCLUSIONS: PIV is a simple and inexpensive biomarker that can be used to estimate mortality in immunosuppressed patients, but the results need to be interpreted carefully.

A new Doppler index, cerebro-placental-uterine ratio, and fetal cardiac parameters in early onset preeclampsia.

OBJECTIVE: Our aim was to investigate the significance of cerebro-placento-uterine ratio CPUR, a new Doppler index, and fetal cardiac parameters (Mod MPI, EFT) in early-onset preeclampsia (EOPE) and to examine whether these parameters are related to perinatal outcome. STUDY DESIGN: Forty participants diagnosed with EOPE (preeclampsia cases diagnosed before 34 weeks of gestation) and 40 healthy pregnant women were included in this study. Demographic data were recorded. Doppler parameters such as middle cerebral artery (MCA), umbilical artery (UA), and uterine artery (Ut-A), and left modified myocardial performance index (Mod-MPI) and epicardial fat thickness (EFT) were measured. Cerebroplacental ratio (CPR) was determined by dividing MCA pulsatility index (PI) by UA PI. CPUR was calculated as the ratio of CPR to mean UtA-PI (CPUR = CPR/UtA-PI). All parameters were compared between the EOPE and control groups. Correlation tests were used to examine the relationship between Doppler parameters and perinatal outcome. p values less than 0.05 were considered statistically significant. RESULTS: The pulsatility index of the middle cerebellar artery, CPUR and CPR values were statistically lower in the EOPE group than in the control group (p = 0.002; p = <0.001; p = <0.001; respectively). No statistical differences were found between groups for isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), ejection time (ET), left mod-MPI, EFT (p = 0.117; p = 0.093; p = 0.398; p = 0.882; p = 0.202, respectively). Umbilical artery Doppler pulsatility index (PI), mean uterine artery Doppler pulsatility index (PI), were higher in the EOPE group than in the control group (p = 0.006; and p = <0.001, respectively). The CPUR value for predicting EOPE was ≤1.3652 with 74. 4% sensitivity and 94.9% specificity. Positive correlations were found between CPUR, CPR, and some neonatal parameters. CONCLUSION: CPUR, a new index combining fetal and uterine Doppler indices, may add contribution to predict adverse perinatal outcome and EOPE.

Evaluation of the relationship between de-novo DSA development and CXCR5+PD-1+CD8+ T cells and PD-1/PD-L1 mRNA expression in kidney transplant recipients.

BACKGROUND AND AIMS: The relationship between the Follicular Cytotoxic T cell subgroup and expression levels of PD1/PD-L1 genes and the development of donor specific antibody (DSA) is unknown. In this study, we aimed to examine CD8+CXCR5+PD-1+ follicular cytotoxic T cell levels and expression levels of PD1/PD-L1 genes in peripheral blood lymphocytes in de-novo DSA positive and negative kidney transplant recipients (KTR). METHODS: In our study, expression of PD-1/ PD-L1 genes by Real-Time Quantitative PCR method and CD8+CXCR5+PD-1+ T cell expression levels by flow cytometric method were obtained from peripheral blood samples. 63 participants were included in the study (de-novo DSA positive recipients (n = 22, group 1), de-novo DSA negative recipients (n = 20, group 2) and healthy control (n = 21, group 3). All patients had negative PRA before kidney transplantation. Expression (%) levels of target cells were evaluated by flow cytometry method. IBM SPSS Statistics for Windows Version 22 and R.3.3.2 software were used to evaluate the data. RESULTS: The demographic data of the groups were similar. PD-1 mRNA expression was higher in de-novo DSA positive KTR than negative (respectively, 1.03 ± .29/.82 ± .15, p: .001). CD8+CXCR5+PD-1+ T cell expression levels were found to be higher in the de-novo DSA positive group than in the negative group and similar to the healthy group (respectively, 3.06 ± 1.98/.52 ± .40, p:.001, 3.06 ± 1.98/2.78 ± .59, p:.62). The percentage of CD8+CXCR5+PD-1+ expressing T cells was significantly lower in the HLA-Class II+ group than other groups (HLA CI/II/ I+II, respectively, 3.63 ± 2.72/1.65 ± .50/3.68 ± 1.67, p: .04). CONCLUSIONS: In our study, a significant relationship was found between DSA formation and PD-1 mRNA level and CD8+CXCR5+PD-1+ follicular cytotoxic T cell in KTR.

Histone acetyltransferase NAA40 modulates acetyl-CoA levels and lipid synthesis.

BACKGROUND: Epigenetic regulation relies on the activity of enzymes that use sentinel metabolites as cofactors to modify DNA or histone proteins. Thus, fluctuations in cellular metabolite levels have been reported to affect chromatin modifications. However, whether epigenetic modifiers also affect the levels of these metabolites and thereby impinge on downstream metabolic pathways remains largely unknown. Here, we tested this notion by investigating the function of N-alpha-acetyltransferase 40 (NAA40), the enzyme responsible for N-terminal acetylation of histones H2A and H4, which has been previously implicated with metabolic-associated conditions such as age-dependent hepatic steatosis and calorie-restriction-mediated longevity. RESULTS: Using metabolomic and lipidomic approaches, we found that depletion of NAA40 in murine hepatocytes leads to significant increase in intracellular acetyl-CoA levels, which associates with enhanced lipid synthesis demonstrated by upregulation in de novo lipogenesis genes as well as increased levels of diglycerides and triglycerides. Consistently, the increase in these lipid species coincide with the accumulation of cytoplasmic lipid droplets and impaired insulin signalling indicated by decreased glucose uptake. However, the effect of NAA40 on lipid droplet formation is independent of insulin. In addition, the induction in lipid synthesis is replicated in vivo in the Drosophila melanogaster larval fat body. Finally, supporting our results, we find a strong association of NAA40 expression with insulin sensitivity in obese patients. CONCLUSIONS: Overall, our findings demonstrate that NAA40 affects the levels of cellular acetyl-CoA, thereby impacting lipid synthesis and insulin signalling. This study reveals a novel path through which histone-modifying enzymes influence cellular metabolism with potential implications in metabolic disorders.

The relationship between COVID-19 and HLA in kidney transplant recipients, an evaluation of predictive and prognostic factors.

INTRODUCTION: The purpose of this study was to determine the predictive and prognostic factors for COVID-19 infection and its relationship with human leukocyte antigen (HLA) in kidney transplant recipients. MATERIAL AND METHOD: Three hundred fifty kidney transplant recipients were included in the study. Recipients were divided into two groups: COVID-19(+) (n = 100) and control (n = 250). The relationships between HLA frequencies, COVID-19 infection, and prognostic factors (age, donor type, immunosuppression protocol, etc.) were then evaluated. Logistic regression analysis, heatmap, and decision tree methods were used to determine predictive and prognostic factors. The study was performed retrospectively. RESULTS: Advanced age and deceased transplantation emerged as predictive of SARS-CoV-2 infection, while the presence of HLA-A*11, the HLA match ratio, and high-dose tacrolimus were identified as prognostic factors in kidney transplant recipients. HLA-A10, HLA-B*13, HLA-B22, and HLA-B*55 were shown to be associated with SARS-CoV-2 infection at univariate analysis, and HLA-B*57, HLA-DRB1*11, and HLA-DRB1*13 at logistic regression analysis. CONCLUSION: HLA-A10, HLA-B*13, HLA-B*55, HLA-B*57, HLA-DRB1*11, and HLA-DRB1*13 were identified for the first time in the literature associated with SARS-CoV-2 infection in kidney transplant recipients.

Consideration of difficulties and exit strategies in a case of face allotransplantation resulting in failure.

We describe the first rescue procedure in a case of total face allotransplantation. The recipient was a 54-year-old man with severe disfigurement of the entire face following an accidental gunshot injury 5 years previously. The large defect included the maxilla, mandible, and mid-face. Full face procurement was performed from a multiorgan cadaveric donor and was allotransplanted to the recipient. The post-transplant induction immunosuppressive regimen included ATG combined with tacrolimus, mycophenolate mofetil, and prednisone, while maintenance was provided by the last three of these. Although the early postoperative period was uneventful, squamous cell carcinoma developed in the upper and lower extremities in the fifth postoperative month, and post-transplant lymphoproliferative disorder (PTLD) occurred in the sixth month postoperatively. Malignancies were treated, involving both surgical and medical approaches. The patient developed opportunistic pulmonary and cerebellar aspergillosis. In order to reduce the adverse affects and metabolic and immunological load, the transplanted face was removed and replaced with a free flap. Although the early postoperative period was promising, with the transferred flap surviving totally and all vital signs and general status appearing to be improving, the patient was eventually lost due to complicated infectious and metabolic events. Although this case was unsuccessful, we suggest that the immunological and metabolic load should be reduced as soon as stable medical conditions are established in case of diagnosis of a situation involving a high rate of mortality, such as PTLD and untreatable opportunistic infections. This should include withdrawal of all immunosuppressive drugs and removal of all allotransplanted tissues.

Association of interleukin 18-607A/C and -137C/G polymorphisms with oxidative stress in renal transplant recipients.

Objectives IL-18 mediates various inflammatory and oxidative responses including renal injury, fibrosis, and graft rejection. It has been reported that the promoter -607 and -137 polymorphisms of IL-18 influence the level of IL-18. This prospective observational study investigated the association between oxidative stress with IL-18-607 and -137 polymorphisms in renal transplant recipients. Patients and methods This study included 75 renal transplant recipients (28 female, 47 male) from living-related donors. Blood samples were collected immediately before and after transplantation at day 7 and month 1. Serum IL-18, creatinine, cystatin C, CRP, and oxidative stress markers (TOS, TAC) were measured. The Oxidative Stress Index (OSI) was calculated. Polymorphisms of the promoter region of the IL-18 gene, IL18-607A/C, and -137C/G were determined by analysis of a "real-time PCR/Melting curve". Results Serum creatinine, cystatin C, CRP, IL-18, TOS, and OSI levels significantly decreased after transplantation. Post-transplant levels of serum TAC and estimated GFR demonstrated consistent significant increases. Serum IL-18 levels were significantly higher in patients with IL-18-137 GG and IL-18-607 CC genotypes before transplantation. Conclusion Our results indicate that the IL-18-137 GG and -607 CC genotypes contribute to higher IL-18 levels; however, the influence of these polymorphisms on oxidative stress has not been observed.

Left ventricle ejection fraction may predict mortality in renal transplant patients.

PURPOSE: Mortality is a major problem in renal transplant patients, and appropriate preoperative evaluation is very important. We retrospectively reviewed the left ventricle ejection fraction (LVEF) of renal transplant patients. MATERIAL AND METHODS: The clinical records of 1763 patients who had preoperative LVEF results and who underwent renal transplantation at Akdeniz University Faculty of Medicine during the years 2004-2014 were studied. The LVEF limit was set at 55%. LVEF, age, gender, diabetes mellitus, hypertension, type of dialysis were assessed by linear multiple regression analysis on survival. RESULTS: There were a total of 1763 renal transplant patients. Those with LVEF of <55% were identified as having left ventricular dysfunction. The mean LVEF was 59.4 ± 9.1 in the 43 patients who died after renal transplantation, while it was 62.6 ± 7.4 in the survivors (p = 0.02). The mortality rate in the LVEF < 55% group was 6.8% (11/162 patients), while mortality in the LVEF ≥ 55% group was 2% (32/1601 patients, p < 0.001). LVEF was found to be the most powerful variable on survival by the linear multiple regression analysis, R2 = 0.05, p < 0.001. CONCLUSION: LVEF may predict mortality in renal transplant patients. LVEF is known to be lower in patients with high cardiac mortality, who may require greater modifications of the postoperative risks.

[Monitoring of cytomegalovirus-specific CD4+ and CD8+ T cell responses by cytokine flow cytometry in renal transplant recipients]. / Böbrek nakil hastalarinda sitomegalovirusa özgül CD4+ ve CD8+ T hücre yanitinin sitokin akim sitometri yöntemiyle izlemi.

In spite of the improvements in the clinical management of solid organ transplant (SOT) recipients provided by immunosuppresion and universal prophylaxis, human cytomegalovirus (CMV) infections continue to be one of the most leading causes of morbidity and mortality. Cell-mediated immunity specific to CMV (CMV-CMI) plays an important role in the control of CMV replication. Therefore, monitoring of CMV-specific T-cell response can be used to predict individuals at increased risk of CMV disease. The aim of this study was to investigate the levels of CMV-specific interferon (IFN)-γ producing CD4(+) and CD8(+) T cells in kidney transplant recipients before and after the transplantation, by cytokine flow cytometry. A total of 21 kidney transplant recipients (14 male, 7 female; age range: 18-66 years, mean age: 34.5 ± 9.9) who were all CMV seropositive have been evaluated in the study. Blood samples from the patients were obtained before and at the 1(st), 3(rd) and 6(th) months after transplantation. CMV seropositive healthy kidney donors (n= 20) constituted the control group. The main stages of our procedure were as follows; isolation of peripheral blood mononuclear cells from whole blood, freezing and storing of the samples, later on thawing the samples, ex vivo stimulation of lymphocytes with pooled CMV peptides and counting CMV-specific IFN- producing CD4(+) and CD8(+) T cells by flow cytometry following surface and intracellular cytokine staining. Monitoring of the viral load (CMV-DNA) was performed in 10 days intervals in the first 3 months followed by 3 week intervals until 6 months using COBAS AmpliPrep/COBAS TaqMan CMV test system (Roche Diagnostics, USA). The frequencies of pretransplant CMV-specific IFN-γ producing CD8(+) T cells in patient (3.53 ± 4.35/µl) and control (4.52 ± 5.17/µl) groups were not statistically different (p= 0.266). The difference between the number of virus-specific CD4(+) T cells in patients (8.84 ± 9.56/µl) and those in the control group (8.23 ± 11.98/µl) was at the borderline of significance (p= 0.057). The age and gender of the patients and type of antiviral prophylaxis protocols [valgancyclovir (n= 4); valacyclovir (n= 17)] did not have any significant effect on CMV-CMI (p> 0.05). Similarly, induction therapy administered to four patients did not show any effect on CMV-CMI (p> 0.05). CMV-specific immune responses of patients who received different immunosuppression protocols [tacrolimus + mycophenolate mofetil (MMF) + steroid (n= 17); cyclosporine + MMF + steroid (n= 2); mTOR inhibitor + MMF + steroid (n= 2)] were not different (p> 0.05). The number of CMV-specific CD4(+) T cells in all patients were significantly decreased in the 3rd month compared to the 1st month after the transplantation (p=0.003), indicating a relationship with the period of immunosuppressive therapy. In one of the patients who did not have CMV-specific CD4+ T-cell response but had cytotoxic T-cells (CD8(+) T= 0.6%) before transplantation, CD4(+) T-cell response have developed during monitorization (1.4%, 1.5% and 0.5% in 1st, 3rd and 6th months, respectively), and no viral reactivation was detected. Out of the two patients who had no CD4(+) and CD8(+) T cell response in the 3rd month, one of them developed low level viremia (150 copies/ml) in the 6th month. In this patient the level of CMV-CMI in the 6th month (CD4(+)T + CD8(+)T= 0.9%), have reached higher values than the values obtained before the transplantation (CD4(+) T + CD8(+) T= 0.5%). The viremia was cleared spontaneously in this patient and no antiviral therapy was required. In conclusion, our results suggested that pretransplant and posttransplant monitoring of CMV-specific T-cell responses might be helpful as well as viral load in the clinical management of CMV infection in SOT patients.

Effect of age on the outcome of renal transplantation: A single-center experience.

OBJECTIVES: To analyze the effects of old age on renal transplantation (Tx) results and graft survival, and compared elderly patient population with the young patients. METHODS: A total of 1946 renal transplant were performed from 1537 living and 409 cadaveric donors between 2003 and 2014. The recipients were divided into two groups according to their age at the time of transplantation. The young age group consisted of 18-59-year-old, and the elderly group consisted of the ones ≥ 60 years. RESULTS: Acute rejection was seen in 19.5% of the young age group while this rate was 16.7% in the old age group (p=0.535). DGF was seen in 6.3% of the young age group, and in 13.5% of the old age group (p<0.001). Analysis of the overall survival rates demonstrated that 1.6% of the patients in the young age group and 6.8% of the patients in the old age groups died (p=0.003). CONCLUSIONS: Renal transplant had high graft survival rates in the elderly as in the young patients. However, the risks for complications were higher in the older age group compared to the younger age group. Thus, it is important to make a careful selection among elderly candidates for renal transplantation.

Is Klotho F352V Polymorphism the Missing Piece of the Bone Loss Puzzle in Renal Transplant Recipients?

BACKGROUND: Bone disorders are next to cardiovascular problems in frequency in renal transplant (RT) recipients. Reduction in 1,25-dihydroxycholecalciferol (1,25D) levels is among the reasons causing bone loss in these patients. Klotho (KL) serves as a co-receptor for fibroblast growth factor 23 (FGF23), and functions in vitamin D metabolism. KL polymorphisms have been identified in several studies, and phenylalanine to valine substitution at amino acid position 352 seemed to be important to KL function. We investigated KL F352V polymorphism and its relation with 1,25D levels in RT recipients. METHODS: The study included 25 RT recipients (8 female, 17 male) and 26 (14 female, 12 male) healthy control subjects who were wild (FF) phenotypes in terms of KL F352V polymorphism. RT recipients with (FV, n = 11) and without (FF, n = 14) a heterozygote polymorphism were determined with high resolution DNA melting analysis of KL F352V polymorphism. Serum 1,25D levels were measured using the RIA method. RESULTS: RT recipients with FV phenotype had significantly lower 1,25D levels (17.58 ± 18.38 pg/ml) compared to recipients with FF phenotype (44.91 ± 24.68 pg/ml) and control subjects (28.24 ± 12.13 pg/ml). 1,25D levels in RT recipients with FF phenotype were significantly higher than control subjects. CONCLUSIONS: KL F352V polymorphism may increase the expression of FGF23 co-receptor, KL protein and thus may decrease renal expression of 1α-hydroxylase, and/or stimulate 24-hydroxylase in RT recipients. The resultant decrease 1,25D levels may participate in bone loss in these patients.

Association between graft function and serum TNF-α, TNFR1 and TNFR2 levels in patients with kidney transplantation.

INTRODUCTION: This prospective observational study aimed to assess the relevance of serial postoperative serum TNF-α, TNFR1 and TNFR2 measurements for predicting graft function and acute rejection episodes (AR) after transplantation. MATERIALS AND METHODS: We studied 50 kidney transplant recipients (31 female, 19 male; mean age: 38.36 ± 12.88). Blood samples were collected immediately before and after surgery at day 7, month 1 and month 3. Serum TNF-α, TNFR1 and TNFR2 levels were measured by ELISA using a commercial kit (Invitrogen ELISA). Serum cystatin-C levels were measured by particle-enhanced immunonephelometric method. Glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease-Epidemiology (CKD-EPI) equation. Patients were assigned to their transplant outcomes in terms of acute rejection [AR(+) and AR(-)] and slow (SGF) or immediate graft function (IGF). RESULTS: Among 50 recipients, six had AR(+) and 44 had AR(-), depending on graft function: 17 had SGF and 33 had IGF. Serum creatinine, cystatin-C, TNF-α, TNFR1 and TNFR2 levels demonstrated consistent significantly decreases after transplantation while GFR values had consistent increases (p = 0.001). Pretransplant levels were not statistically different between AR(+) and AR(-) groups (TNF-α: 30.79 ± 5.96 vs. 27.95 ± 2.43 pg/mL, TNFR1: 55.96 ± 21.6 vs. 40.52 ± 7.41 ng/mL, TNFR2: 58.31 ± 8.06 vs. 50.9 ± 3.34 ng/mL, respectively) (p > 0.05). Serum TNF-α, TNFR1 and TNFR2 levels on day 7 and month 1 were also significantly higher in AR(+) group compared to AR(-) (p = 0.012, p = 0.049 for TNF-α, p = 0.001, p = 0.002 for TNFR1, p = 0.001, p = 0.002 for TNFR2). CONCLUSIONS: Our preliminary findings suggest that serum TNF-α, TNFR1 and TNFR2 levels might be considered useful markers of evaluating graft function after renal transplantation.

The association of serum-free light-chain levels with markers of renal function.

BACKGROUND: The kidney is often affected in plasma cell dyscrasias, usually due to the effects of nephrotoxic monoclonal-free light chains. Renal failure due to a monoclonal gammopathy may be detected by the highly sensitive serum-free light-chain (sFLC) ratio yet missed by electrophoretic assays. The aim of this study was to assess sFLC levels in relation to markers of renal function. METHODS: Five-hundred thirteen patients were included in this study. sFLC levels were measured by Freelite® (The Binding Site Group Ltd, Birmingham, UK) assay using the BNII nephelometer (Siemens Diagnostics, Germany). Kappa/lambda (κ/λ) sFLC ratio was calculated. Serum creatinine levels were analyzed by modified Jaffe method in Cobas 8000 analyser. GFR was estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Patients were assigned to two groups depending on their eGFR values: ≤ 60 mL/min/1.73 m(2) (Group 1, n = 103) and > 60 mL/min/1.73 m(2) (Group 2, n = 410). Data were expressed as median and min-max. All the statistical analyses were done with SPSS version 20.0 and a significance level of 0.05 was considered. RESULTS: Serum κ-FLC median value was 36.4 (5.62-16,000) mg/L, serum λ-FLC was 21.7 (4.91-8770) mg/L, κ/λ sFLC ratio was 1.33 (0.01-3258) and serum creatinine was 1.56 (0.63-7.21) mg/dL in Group 1. Both λ sFLC and κ/λ sFLC ratios were correlated with eGFR (r = -0.318, r = 0.198, p < 0.05, respectively). We did not find any significant correlation between κ/λ sFLC ratio and eGFR in Group 2. CONCLUSIONS: We examined the association between sFLC concentrations and renal function. Our preliminary findings suggest that serum λ-FLC might be considered as a useful marker for predicting renal function. Prospective studies are needed to clarify the usefulness of these parameters for identifying renal failure due to a monoclonal gammopathy.

The significance of Syndecan 1, a new marker for endothelial dysfunction, in cases of fetal growth retardation.

PROBLEM: In the current study we aimed to investigate Syndecan 1 (SDC1) levels in pregnant women diagnosed with fetal growth restriction (FGR) and the relationship between SDC1 levels and clinical and doppler parameters in FGR cases associated with endothelial dysfunction, angiogenesis and uteroplacental insufficiency METHOD OF STUDY: A total of 90 pregnant women included in the study, (45 with FGR, 45 healthy control) matched by week of gestation and maternal age. Venous blood samples were collected and plasma concentrations of SDC1 were determined by a specific immunoassay. Doppler examination was performed to evaluate the relationship between the SDC1 levels and placental blood supply. RESULTS: Doppler parameters; mean UtA-PI (p < .001), CPR (p = .002) and CPUR (p < .001) were different between the groups, however MCA PI, umbilical artery PI and umbilical artery S/D were not (p > .05). While gestational age at delivery, birth weight, APGAR score at 1 and 5 min were significantly lower (all, p < .001) in the study group, non-reassure fetal heart rate tracing (p = .09) and NICU admission (p = .02) were significantly higher. SDC 1 level was 2,00 ± 1,47 ng/mL and 2,34 ± 1,12 ng/mL in the FGR and control groups, respectively (p = .008). In the study group SDC 1 level was 1,69 ± 2,00 in those with gestational age below 32 weeks and 2,13 ± 1,18 in those with gestational age above 32 weeks and there was a statistically significant difference between the groups (p = .015). Plasma SDC 1 concentration of 2,1850 ng/mL or less had a sensitivity of 70%, a specificity of 72%, area under the ROC curve .65 (p < .005). CONCLUSIONS: Low maternal plasma SDC1 level may be associated with placental insufficiency and FGR. Low levels of SDC1 may be helpful as a predictor for the development of FGR during gestation.

Acute renal failure due to uterine prolapse: a case report.

Herein, we present a successfully treated case with acute renal failure due to ureteral obstruction caused by total uterine prolapsed. A 55-year-old female patient presented to our hospital with the complaints of protrusion of the uterus for the last 3 months, pollakiuria, nocturia, decreased urine volume, and swelling of her body for the last week, and as well as impaired general status with shortness of breath for the last several days. Her physical examination revealed a blood pressure of 140/90 mmHg, pulse rate of 80 beats/min, body temperature of 37.8 °C, as well as uterine prolapse with infection and erosion on the surface of the uterus, crepitating rales in the basal segments of both lungs, and pretibial edema. Results of laboratory analyses were as follows: BUN = 70 mg/dL, Cr = 6.5 mg/dL, CRP = 8.7 mg/dL, and leukocyte = 12,000/mm(3). Blood gas analysis revealed a pH of 7.35 and bicarbonate level of 14 mmol/L. Data obtained from ultrasonography, DTPA scintigraphy, and abdominal CT, which were performed assuming that the patient had post-renal renal failure due to the compression by uterus, supported this assumption. Bilateral nephrostomy catheters were inserted and appropriate fluid-electrolyte therapy for volume status and antibiotherapy were commenced. Renal functions returned to normal levels on the 4th day of therapy and her complaints disappeared. The patient underwent total abdominal hysterectomy and was monitored in terms of renal functions and diuresis. The present case was presented due to its importance for being a quite rare case who dramatically responded to accurate intervention performed in time.

Protocol for in vivo lineage tracing of the mouse-papillomavirus-type 1-infected cells in mice.

Here, we present a protocol to create an in vivo lineage-tracing mouse model for mouse-papillomavirus-type 1 (MmuPV1)-infected cells. We describe the steps to generate and deliver the MmuPV1 lox-Cre-lox plasmid for the infection of mice, followed by skin tissue extraction and processing. We then detail how to use flow cytometry to trace, quantify, and analyze MmuPV1-harboring cells and their progeny. This model is suitable to investigate the early effects of papillomavirus on the target cells. For complete details on the use and execution of this protocol, please refer to Yilmaz et al. (2022).1.

Evaluation of the effect and predictive role of vitamin D and vitamin D receptor expression in CD4 + , CD8 + , CD14 + , CD56 + cells on the development of chronic rejection and graft functions in kidney transplant patients.

PURPOSE: It is known that vitamin D has positive effects on graft functions (reduce fibrosis, suppress excessive inflammatory response, improve graft functions). In our study, it was aimed to evaluate the effects and predictive roles of vitamin D, the expression of vitamin D receptor (VDR) in lymphocytes, monocytes, natural killer cells on chronic rejection and graft functions in kidney transplant patients. METHODS: Seventy one people were included in the study and analyses were made by dividing them into 3 groups. Group 1: Healthy control (n = 29), Group 2: Kidney transplant patients with stable kidney function (n = 17), and Group 3: Kidney transplant patients with chronic rejection diagnosis (n = 25). Serum 25-hydroxycholecalciferol, 1.25 dihydroxycholecalciferol levels and VDR percentages in CD4 + , CD8 + , CD14 + , CD56 + cells were measured in 3 groups. ROC analyses and logistic regression models were performed to predict rejection and long-term graft functions. RESULTS: The percentage of VDR expression in CD4 + lymphocytes (p < 0.001) and CD14( +) monocytes (p < 0.001), 25-hydroxycholecalciferol and 1.25 dihydroxycholecalciferol levels were lower in group 3 was detected. In ROC analyses and logistic regression models, VDR expression in CD4( +)T lymphocytes was shown to have a statistically significant value in the development of chronic rejection (Odds ratio 0.86: 0.76-0.92; p = 0.001/AUC = 0.941, p < 0.001) and prediction of 5th-year graft functions (Odds ratio 0.93: 0.88-0.98; p = 0.017/AUC = 0.745, p = 0.007). CONCLUSION: In our study, it was shown that low vitamin D and VDR expression is associated with poor outcome and VDR expression in CD4( +)T lymphocytes is predictive in terms of graft function and rejection.

Evaluation of Overall Survival and Disease-Free Survival in Patients Receiving Liver Transplantation for Hepatocellular Carcinoma and Comparison of Living Versus Deceased Donor Liver Transplants: Results of 15 Years of Experience.

OBJECTIVE: Research comparing patients who received liver transplantation (LT) for hepatocellular carcinoma (HCC) has produced varying outcomes regarding survival and disease-free survival. The objective of this study is to determine the factors that influence the disease-free and overall survivals of those who have undergone LT for HCC and to compare the outcomes of living versus deceased donor liver transplants. MATERIALS AND METHODS: We retrospectively analyzed data on patients aged 18 and above who received LT for HCC from 2006 to 2022. Patients with a follow-up period of less than 6 months and who did not meet the University of California San Francisco criteria were excluded. The data from 58 patients were analyzed. We split the patients into living donor liver transplantation (LDLT) (group 1) and deceased donor liver transplantation (DDLT) (group 2). RESULTS: The mean age was 56 ± 8.1 years. There were 49 males and 9 females. The median of the alphafetoprotein (AFP) level and model for end-stage liver disease score was 10.1 ng/mL and 11, respectively. The 1-, 3-, 5-, and 10-year disease-free survival rates were 86%, 76.5%, 76.5%, and 76.5%, respectively. The survival rates for the same periods were 94.8%, 74.9%, 70.6%, and 67.4%. The receiver operating characteristic analysis revealed that AFP > 31.8 ng/mL and a total tumor size >3.85 cm raise the likelihood of HCC recurrence post-LT. CONCLUSION: Based on the current literature, the overall survival and disease-free survival rates are influenced by factors such as AFP value, total tumor number, and total tumor diameter. In our study, the AFP value and total tumor size had an impact on the recurrence of HCC, and the survival rates were comparable on LDLT and DDLT.

Predictive Factors of BK Virus Development in Kidney Transplant Recipients and the Effect of Low-Dose Tacrolimus Plus Everolimus on Clinical Outcomes.

OBJECTIVES: This study aimed to determine the predictive factors of BK virus viremia/nephropathy in kidney transplant recipients and to evaluate the effects of low-dose tacrolimus plus everolimus. MATERIALS AND METHODS: This study included 3654 kidney transplant recipients. The patients were divided into 2 groups: group 1 were BK virus negative (n = 3525, 96.5%) and group 2 were BK virus positive (n = 129, viremia 3.5%, nephropathy 1%). Predictive factors were determined by receiver operating characteristic curve analysis and logistic regression models.We also divided and analyzed patients with BK virus viremia/nephropathy into 2 groups according to immunosuppressive changes. Group 2a had been switched to low-dose tacrolimus plus everolimus (n = 54, 41.9%), and group 2b had been switched to other immunosuppressive protocols (n = 75, 58.1%). RESULTS: We found that use of anti-T-cell lymphocyte globulin and tacrolimus, deceased donor transplant, and rejection were predictive factors for BK virus viremia/nephropathy. In addition, patients who had low-dose calcineurin inhibitor plus mammalian target of rapamycin inhibitor regimens showed a low rate of BK virus development(only 6.2% of all cases). In Group 2a, both the BK polyomavirus-associated nephropathy rate (n = 23 [42.6%] vs n = 12 [16%] in group 2b; P = .001) and viral load (DNA > 104 copies/mL) (n = 49 [90.7%] vs n = 27 [36%] in group 2b; P = .001) were increased versus group 2b. Graft function, graft survival, viral clearance, and rejection rate were similar between the groups after protocol change. CONCLUSIONS: BK virus viremia/nephropathy rate was lower in patients who received low-dose calcineurin inhibitor plus mammalian target of rapamycin inhibitor protocols; the low-dose tacrolimus plus everolimus switch protocol after BK virus was more effective and safe than other protocols.

Regulatory B Cells Profile in Kidney Transplant Recipients With Chronic-Active Antibody-Mediated Rejection.

This study aims to reveal the relationship between regulatory B cell (Breg) subsets and chronic-active antibody-mediated rejection (c-aABMR) in renal transplant recipients. Our study involved 3 groups of participants: renal transplant recipients with biopsy-proven c-aABMR as the chronic rejection group (c-aABMR, n = 23), recipients with stable graft functions as the patient control group (PC; n = 11), and healthy volunteers (HV; n = 11). Breg subsets, immature/transitional B cells, plasmablastic cells, B10 cells, and BR1 cells were isolated from venous blood samples by flow cytometry. The median values of Breg frequencies in the total lymphocyte population were analyzed. There were no significant differences between the study groups for immature and/or transitional B cell frequencies. Plasmablastic cell frequencies of the c-aABMR group (7.80 [2.10-27.40]) and the PC group (6.00 [1.80-55.50]) were similar, but both of these values were significantly higher than the HVs' (3.40 [1.20-8.50]), (respectively, P = .005 and P = .039). B10 cell frequencies were also similar, comparing the c-aABMR (4.20 [0.10-7.40]) and the PC groups (4.10 [0.10-5.90]), whereas the HVs (5.90 [2.90-8.50]) had the highest B10 cell frequency with an only statistical significance against the PC group (respectively, P = .09 and P = .028). The c-aABMR and the PC groups were similar regarding BR1 cell frequencies. However, the HV group significantly had the highest frequency of BR1 cells (5.50 [2.80-10.80]) than the other groups (P < .001 for both). We demonstrated that frequencies of B10 and BR1 cells were higher in HVs than in transplant recipients, regardless of rejection state. However, there was no significant relation between Breg frequencies and the c-aABMR state.