Orchestrating the Impact of KIR/HLA Interactions on Kidney Transplant.

This study examines the interplay between human leukocyte antigen (HLA) compatibility and killer-cell immunoglobulin-like receptor (KIR) genotypes in influencing kidney transplantation outcomes. Understanding these interactions is crucial for improving graft survival and minimizing rejection risks. We evaluated 84 kidney transplant recipients, dividing them into two groups based on post-transplant outcomes: there were 68 with stable graft function (SGF) and 16 who experienced chronic rejection (CR). Patients were selected based on specific inclusion criteria. HLA mismatches (Class I: HLA-A, -B; Class II: HLA-DR) and KIR genotypes were determined using standard genotyping techniques. Statistical analyses, including logistic regression, were performed to correlate these factors with transplant outcomes. Significant age differences were observed, with younger patients more likely to experience graft rejection, while no significant gender-based differences were noted. A significant correlation was found between Class II mismatches and increased rejection rates, highlighting the importance of HLA-DR compatibility. Further analysis revealed that certain inhibitory KIRs, such as KIR3DL1, were associated with favorable outcomes, suggesting a protective role against graft rejection. These findings were corroborated by evaluating serum creatinine levels over multiple years, serving as a biomarker for renal function post transplant. This study underscores the critical need for meticulous HLA matching and the consideration of KIR genotypes in pre-transplant evaluations to enhance graft survival and minimize rejection risks. Integrating these genetic factors into routine clinical assessments could significantly improve personalized transplant medicine strategies, ultimately enhancing patient outcomes. Further research is needed to explore the underlying mechanisms and validate these findings in larger, diverse populations.

Investigating Potential Correlations between Calcium Metabolism Biomarkers and Periprocedural Clinical Events in Major Cardiovascular Surgeries: An Exploratory Study.

Background: There is emerging but conflicting evidence regarding the association between calcium biomarkers, more specifically ionized calcium and the prognosis of intensive care unit (ICU) postoperative cardiac patients. Methods: Our study investigated the relationship between ionized calcium, vitamin D, and periprocedural clinical events such as cardiac, neurologic and renal complications, major bleeding, vasoactive-inotropic score (VIS), and length of ICU and hospitalization. Results: Our study included 83 consecutive subjects undergoing elective major cardiac surgery requiring cardiopulmonary bypass. The mean age of the participants was 64.9 ± 8.5 years. The majority of procedures comprised isolated CABG (N = 26, 31.3%), aortic valve procedures (N = 26, 31.3%), and mitral valve procedures (N = 12, 14.5%). A difference in calcium levels across all time points (p < 0.001) was observed, with preoperative calcium being directly associated with intraoperative VIS (r = 0.26, p = 0.016). On day 1, calcium levels were inversely associated with the duration of mechanical ventilation (r = -0.30, p = 0.007) and the length of hospital stay (r = -0.22, p = 0.049). At discharge, calcium was inversely associated with length of hospital stay (r = -0.22, p = 0.044). All calcium levels tended to be lower in those who died during the 1-year follow-up (p = 0.054). Preoperative vitamin D levels were significantly higher in those who experienced AKI during hospitalization (median 17.5, IQR 14.5-17.7, versus median 15.3, IQR 15.6-20.5, p = 0.048) Conclusion: Fluctuations in calcium levels and vitamin D may be associated with the clinical course of patients undergoing cardiac surgery. In our study, hypocalcemic patients exhibited a greater severity of illness, as evidenced by elevated VIS scores, and experienced prolonged mechanical ventilation time and hospital stays. Additional larger-scale studies are required to gain a deeper understanding of their impact on cardiac performance and the process of weaning from cardiopulmonary bypass, as well as to distinguish between causal and associative relationships.

Efficiency of Simulation-Based Learning Using an ABC POCUS Protocol on a High-Fidelity Simulator.

Critically ill patients with rapidly deteriorating clinical status secondary to respiratory and cardio-vascular compromise are at risk for immediate collapse if the underlying pathology is not recognized and treated. Rapid diagnosis is of utmost importance regardless of the setting. Although there are data to support the use of point-of-care ultrasound in critical patients, there is no consensus about the best educational strategy to implement. We designed a curriculum based on the ABC (Airway, Breathing, Circulation) protocol that covers essential airway, lung, and cardiac ultrasound skills needed for fast diagnosis in critical patients and applied it in high-fidelity simulation-based medical education sessions for anesthesia and intensive care residents year one and two. After theoretical and practical assessments, our results show statistical differences in the theoretical knowledge and above-average results in practical assessment. Our proposed curriculum based on a simple ABC POCUS protocol, with an Airway, Breathing, and Circulation approach, is useful in teaching ultrasound basics regarding airway, lung, and cardiac examination using high-fidelity simulation training to anesthesia and intensive care residents, but further research is needed to establish the utility of Simulation-Based Medical Education in Point of Care Ultrasound in the critical patient.

An Integrated Approach Using HLAMatchmaker and Pirche II for Epitopic Matching in Pediatric Kidney Transplant-A Romanian Single-Center Study.

(1) Background: Renal transplantation (KT) is the most efficient treatment for chronic kidney disease among pediatric patients. Antigenic matching and epitopic load should be the main criteria for choosing a renal graft in pediatric transplantation. Our study aims to compare the integration of new histocompatibility predictive algorithms with classical human leukocyte antigen (HLA) matching regarding different types of pediatric renal transplants. (2) Methods: We categorized our cohort of pediatric patients depending on their risk level, type of donor and type of transplantation, delving into discussions surrounding their mismatching values in relation to both the human leukocyte antigen Matchmaker software (versions 4.0. and 3.1.) and the most recent version of the predicted indirectly identifiable HLA epitopes (PIRCHE) II score. (3) Results: We determined that the higher the antigen mismatch, the higher the epitopic load for both algorithms. The HLAMatchmaker algorithm reveals a noticeable difference in eplet load between living and deceased donors, whereas PIRCHE II does not show the same distinction. Dialysis recipients have a higher count of eplet mismatches, which demonstrates a significant difference according to the transplantation type. Our results are similar to those of four similar studies available in the current literature. (4) Conclusions: We suggest that an integrated data approach employing PIRCHE II and HLAMatchmaker algorithms better predicts histocompatibility in KT than classical HLA matching.

The immunologically high-risk kidney recipient in the early post-COVID-19 period. To do or not to do? A case report.

Kidney transplantation is nowadays the treatment of choice for end-stage kidney disease (ESKD), and it is the most performed organ transplantation. During the COVID-19 pandemic, kidney-transplant recipients appeared to be at higher risk of morbidity and mortality due to severe forms of illness. The result was a decrease in the number of solid organs transplants worldwide, with patients' reduced chance of receiving transplants. The best timing for surgery after COVID-19 infection is still controversial since most of the available data come from study periods with zero or low prevalence of vaccination and COVID-19 variants with high mortality rates. The American Society of Anesthesiologists (ASA) and the Anesthesia Patient Safety Foundation (APSF) Joint Statement on Elective Surgery/Procedures and Anesthesia for Patients after COVID-19 Infection states that elective surgery should be delayed for 7 weeks after a SARS-CoV-2 infection in unvaccinated patients while making no clear statement for vaccinated ones, or those which have already been infected with the virus. Kidney transplant, as opposed to tissue transplant, is not an elective surgery, so the question raised is whether to do it or not. We present the case of a hyper-immunized 47-year-old male patient with end-stage chronic kidney disease who received a second kidney transplant, despite having a mild SARS-COV 2 infection just 2 weeks before his transplantation surgery.

The Use of Machine Learning Algorithms and the Mass Spectrometry Lipidomic Profile of Serum for the Evaluation of Tacrolimus Exposure and Toxicity in Kidney Transplant Recipients.

Tacrolimus has a narrow therapeutic window; a whole-blood trough target concentration of between 5 and 8 ng/mL is considered a safe level for stable kidney transplant recipients. Tacrolimus serum levels must be closely monitored to obtain a balance between maximizing efficacy and minimizing dose-related toxic effects. Currently, there is no specific tacrolimus toxicity biomarker except a graft biopsy. Our study aimed to identify specific serum metabolites correlated with tacrolinemia levels using serum high-precision liquid chromatography-mass spectrometry and standard laboratory evaluation. Three machine learning algorithms were used (Naïve Bayes, logistic regression, and Random Forest) in 19 patients with high tacrolinemia (8 ng/mL) and 23 patients with low tacrolinemia (5 ng/mL). Using a selected panel of five lipid metabolites (phosphatidylserine, phosphatidylglycerol, phosphatidylethanolamine, arachidyl palmitoleate, and ceramide), Mg2+, and uric acid, all three machine learning algorithms yielded excellent classification accuracies between the two groups. The highest classification accuracy was obtained by Naïve Bayes, with an area under the curve of 0.799 and a classification accuracy of 0.756. Our results show that using our identified five lipid metabolites combined with Mg2+ and uric acid serum levels may provide a novel tool for diagnosing tacrolimus toxicity in kidney transplant recipients. Further validation with targeted MS and biopsy-proven TAC toxicity is needed.

COVID-19 and kidney transplantation: the impact of remdesivir on renal function and outcome - a retrospective cohort study.

OBJECTIVES: The aim of the study was to evaluate the impact of remdesivir on overall mortality, ICU mortality, and renal functional outcome in hospitalized patients with COVID-19 who received kidney transplant. METHODS: We reviewed 165 patients with KTx hospitalized owing to COVID-19 between March 1, 2020, and May 31, 2021. A total of 38 patients with KTx received a 5-day RDV treatment, whereas 127 received standard of care (SOC). Overall and ICU mortality along with functional outcome were assessed. RESULTS: The 2 groups had similar baseline characteristics. RDV treatment was completed in all patients without any adverse effects attributable to RDV. In terms of overall mortality, there was no difference between the RDV and SOC groups (18% vs 23%, p >0.05), but the ICU mortality was significantly reduced in the RDV group (39% vs 83%, p <0.05). RDV seems to have no nephrotoxic effect on patients with KTx because there was no difference in the incidence of AKI between RDV and SOC groups (50% vs 43%, p >0.05), and the discharge eGFR values significantly improved in the RDV group compared with the admission values (57 ± 23 vs 44 ± 22, p <0.05). CONCLUSION: Five-day RDV treatment appears safe in KTx recipients, and without obvious nephrotoxic effects. Also, RDV may decrease ICU mortality attributed to COVID-19.

SERS Liquid Biopsy Profiling of Serum for the Diagnosis of Kidney Cancer.

Renal cancer (RC) represents 3% of all cancers, with a 2% annual increase in incidence worldwide, opening the discussion about the need for screening. However, no established screening tool currently exists for RC. To tackle this issue, we assessed surface-enhanced Raman scattering (SERS) profiling of serum as a liquid biopsy strategy to detect renal cell carcinoma (RCC), the most prevalent histologic subtype of RC. Thus, serum samples were collected from 23 patients with RCC and 27 controls (CTRL) presenting with a benign urological pathology such as lithiasis or benign prostatic hypertrophy. SERS profiling of deproteinized serum yielded SERS band spectra attributed mainly to purine metabolites, which exhibited higher intensities in the RCC group, and Raman bands of carotenoids, which exhibited lower intensities in the RCC group. Principal component analysis (PCA) of the SERS spectra showed a tendency for the unsupervised clustering of the two groups. Next, three machine learning algorithms (random forest, kNN, naïve Bayes) were implemented as supervised classification algorithms for achieving discrimination between the RCC and CTRL groups, yielding an AUC of 0.78 for random forest, 0.78 for kNN, and 0.76 for naïve Bayes (average AUC 0.77 ± 0.01). The present study highlights the potential of SERS liquid biopsy as a diagnostic and screening strategy for RCC. Further studies involving large cohorts and other urologic malignancies as controls are needed to validate the proposed SERS approach.

Favipiravir in Kidney Transplant Recipients With COVID-19: A Romanian Case Series.

BACKGROUND: Favipiravir (FPV) is an orally administrable antiviral drug that selectively inhibits RNA-dependent RNA polymerase and has been repurposed for COVID-19 treatment. There is limited information on the use of FPV in kidney transplant recipients (KTx), who often have multiple comorbidities and run a higher risk for death from COVID-19. METHODS: We retrospectively reviewed all KTx at our institution who got sick with COVID-19 between March 1, 2020, and May 31, 2021, and who received FPV (loading dose of 1800 mg × 2 on day 1, maintenance dose 2  ×  800 mg/d for 5-14 days) as part of their COVID treatment. We analyzed demographics, clinical course, laboratory data, management, and outcome. RESULTS: Nine KTx with COVID-19 received FPV; all were hospitalized. The median age was 52 years (range, 32-60 years), and women were predominant (77.7%). Eight KTx had pulmonary involvement on chest radiograph. On admission 1 patient had mild, 5 had moderate, 2 had severe, and 1 had critical disease. Leukopenia and increased creatinine were universally noted. Three patients had disease progression under treatment. Seven patients (77.7%) required additional oxygen, and 4 (57.1%) needed intensive care unit admission. Three KTx died, resulting in an overall mortality of 33.3%. Survivors did not show increased transaminases or creatinine during or after FPV treatment; leukocytes, neutrophils, and platelets improved on discharge compared with admission values. CONCLUSIONS: FPV appears well tolerated by KTx with COVID-19, but its clinical benefit remains unclear. Larger analyses are needed.

Case Report: Acute Splenic Artery Thrombosis in a COVID 19, Postpartum Patient.

The incidence of thromboembolic disease is reported to be high in SARS-CoV2 disease. Pregnancy, an already physiologically hypercoagulable state, associated to COVID 19, generates even more concern regarding the potentially increased risk of thrombotic events. The exact incidence of such complications is yet unknown, but there is data suggesting that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Since the outbreak of the COVID 19 pandemics, the most common described thrombotic events associated with SARS-COV2 infection have been venous thromboembolism and disseminated intravascular coagulation, while arterial thrombotic events are less commonly described. Splenic infarction is a rare disorder that can be secondary to a hypercoagulable state. There are only few cases of splenic infraction described, but none with splenic artery thrombosis, in a post-partum patient, on therapeutic anticoagulation regimen. We present the case of a 31-year-old Caucasian, 26 weeks pregnant woman, with no prior medical history, admitted to the hospital with a severe form of COVID 19 pneumonia and who, during the course of the disease, developed a massive splenic infarction with splenic artery thrombosis.

Hemodynamic Predictors for Sepsis-Induced Acute Kidney Injury: A Preliminary Study.

The aim of our study was to assess the association between the macrohemodynamic profile and sepsis induced acute kidney injury (AKI). We also investigated which minimally invasive hemodynamic parameters may help identify patients at risk for sepsis-AKI. We included 71 patients with sepsis and septic shock. We performed the initial fluid resuscitation using local protocols and continued to give fluids guided by the minimally invasive hemodynamic parameters. We assessed the hemodynamic status by transpulmonary thermodilution technique. Sequential organ failure assessment (SOFA score) (AUC 0.74, 95% CI 0.61-0.83, p < 0.01) and cardiovascular SOFA (AUC 0.73, 95% CI 0.61-0.83, p < 0.01) were found to be predictors for sepsis-induced AKI, with cut-off values of 9 and 3 points respectively. Persistent low stroke volume index (SVI) ≤ 32 mL/m2/beat (AUC 0.67, 95% CI 0.54-0.78, p < 0.05) and global end-diastolic index (GEDI) < 583 mL/m2 (AUC 0.67, 95% CI 0.54-0.78, p < 0.05) after the initial fluid resuscitation are predictive for oliguria/anuria at 24 h after study inclusion. The combination of higher vasopressor dependency index (VDI, calculated as the (dobutamine dose × 1 + dopamine dose × 1 + norepinephrine dose × 100 + vasopressin × 100 + epinephrine × 100)/MAP) and norepinephrine, lower systemic vascular resistance index (SVRI), and mean arterial blood pressure (MAP) levels, in the setting of normal preload parameters, showed a more severe vasoplegia. Severe vasoplegia in the first 24 h of sepsis is associated with a higher risk of sepsis induced AKI. The SOFA and cardiovascular SOFA scores may identify patients at risk for sepsis AKI. Persistent low SVI and GEDI values after the initial fluid resuscitation may predict renal outcome.

Does norepinephrine infusion dose influence the femoral-to-radial mean arterial blood pressure gradient in patients with sepsis and septic shock?

The aim of our study is to determine whether there is a clinically important difference between the femoral and the radial site of blood pressure measurements, and to identify whether the vasoactive infusion dose influences the femoral-to-radial mean arterial blood pressure (MAP) gradient. We included 71 patients with sepsis and septic shock, with no comorbidities that may influence the hemodynamic parameters. Simultaneous measurements were registered at the femoral and radial arteries. The agreement between the two sites of recording was tested in the no-norepinephrine, low-norepinephrine, and high-norepinephrine groups, as well as for the whole group. Results show that 75.4% of paired recordings have a gradient of at least 5 mmHg between the femoral and radial recordings. For the measurements that have a gradient more than 5 mmHg, norepinephrine infusion dose was not found to be a determining factor. A better level of agreement was found after carrying out a separate Bland-Altman analysis for the femoral-to-radial and radial-to-femoral gradients. Norepinephrine infusion rate was not found to be a determining factor for the femoral-to-radial MAP gradient in septic and septic shock patients. Measurement of MAP at the radial or femoral site is clinically interchangeable for most of these patients.

Initial Fluid Resuscitation Following Adjusted Body Weight Dosing in Sepsis and Septic Shock.

INTRODUCTION: Fluid administration is considered a fundamental part of early sepsis treatment. Despite abundant research, fundamental questions about the amount of fluids to be given remain unanswered. Recently, the idea of adjusting the fluid load to the ideal body weight emerged, as obesity rates are increasing, and fluid overload was proven to increase mortality. AIM OF THE STUDY: The study aimed to determine whether advanced haemodynamic monitoring supports the adjustment of the initial fluid load to the ideal body weight (IBW). METHODS: Seventy-one patients with sepsis and septic shock were enrolled in the study. The initial fluid resuscitation was performed using local protocols. The haemodynamic status was assessed after the initial fluid load by transpulmonary thermos-dilution technique and the renal outcome recorded at twenty-four hours. RESULTS: 68.6% of the patients included in the study had weight disorders ranging from BMI+20% to morbid obesity. Before IBW adjustment, only 49.3% received the 30 ml/kg fluid load recommended by Surviving Sepsis Campaign Guidelines (2016) (SSC). After IBW adjustment, 70.4% received the recommended fluid dose. The difference in fluid load/kg before and after the bodyweight adjustment was statistically significant (p<0.01). After the initial fluid load, the majority of the macro haemodynamic parameters were in the targeted range. There was no statistically significant difference between the urinary output outcome at 24 hours or the 28 days mortality rates between the patients resuscitated by the SSC and those who received less fluid. CONCLUSIONS: Advanced haemodynamic monitoring was in favour of adjusting the initial fluid load to the IBW. There were no statistically significant differences either in the urinary output outcome at twenty-four hours, or in the twenty-eight-day mortality rates between the patients who received the 30 ml/kg IBW and those who received less than 30 ml/kg IBW.

Assessment of method agreement between two minimally invasive hemodynamic measurements in septic shock patients on high doses of vasopressor drugs. A preliminary study.

BACKGROUND: Minimally invasive hemodynamic monitoring is still controversial among the methods used to assess the hemodynamic profile of the septic shock patient. The aim of this study was to test the level of agreement between two different devices. METHODS: We collected 385 data entries during 12-hour intervals from four critically ill patients with septic shock and high doses of vasoactive therapy using two minimally invasive methods at the same time: Vigileo™ device which uses the pulse contour principle, and EV1000™ monitoring platform which uses the transpulmonary thermodilution principle. The studied parameters were Stroke Volume (SV), Cardiac Output (CO) and Mean Arterial Pressure (MAP). We tested the agreement by performing the visual examination of data patterns using graphs and studying the bias, limits of agreement and creating Bland-Altman plots. For assessing the systematic, proportional and random differences, we computed a Passing-Bablock regression with the CUSUM test for linearity. RESULTS: The one sample t-Test for the differences between the two methods against the null value was statistically significant for the studied parameters (p < 0.0001). The Bland-Altman analysis found no agreement between the data obtained using the two techniques, with calculated error percent as high as 88.28% for SV, 82.02% for CO and 42.06% for MAP. The Passing-Bablock regression analysis tested positive for systematic differences, but this could not be accounted for. CONCLUSION: We found no agreement between data obtained from the studied devices; therefore, these cannot be used interchangeably for critically ill septic shock patients on high doses of vasoactive substances.

Lethal case of Vipera bersus bite.

Adder bites are rare events, but they can be fatal. Three adder types live in Romania - Vipera ammodytes, Vipera ursini and Vipera berus. Most adder bites happen during the summer with a peak incidence between July and August. Here we present the case of a 56 years old male patient who was bitten by an adder. The clinical presentation was severe from the beginning with a GCS of 3 points, respiratory and cardiovascular failure; despite of adequate treatment the patient developed multiorgan dysfunction and died 36 hours after the ICU admission. The aim of this report is to raise awareness that snake bites can have a life-threatening course and need immediate attention and medical care.