Role of AI and Radiomic Markers in Early Diagnosis of Renal Cancer and Clinical Outcome Prediction: A Brief Review.

Globally, renal cancer (RC) is the 10th most common cancer among men and women. The new era of artificial intelligence (AI) and radiomics have allowed the development of AI-based computer-aided diagnostic/prediction (AI-based CAD/CAP) systems, which have shown promise for the diagnosis of RC (i.e., subtyping, grading, and staging) and prediction of clinical outcomes at an early stage. This will absolutely help reduce diagnosis time, enhance diagnostic abilities, reduce invasiveness, and provide guidance for appropriate management procedures to avoid the burden of unresponsive treatment plans. This survey mainly has three primary aims. The first aim is to highlight the most recent technical diagnostic studies developed in the last decade, with their findings and limitations, that have taken the advantages of AI and radiomic markers derived from either computed tomography (CT) or magnetic resonance (MR) images to develop AI-based CAD systems for accurate diagnosis of renal tumors at an early stage. The second aim is to highlight the few studies that have utilized AI and radiomic markers, with their findings and limitations, to predict patients' clinical outcome/treatment response, including possible recurrence after treatment, overall survival, and progression-free survival in patients with renal tumors. The promising findings of the aforementioned studies motivated us to highlight the optimal AI-based radiomic makers that are correlated with the diagnosis of renal tumors and prediction/assessment of patients' clinical outcomes. Finally, we conclude with a discussion and possible future avenues for improving diagnostic and treatment prediction performance.

Center-driven and Clinically Driven Variation in US Liver Transplant Maintenance Immunosuppression Therapy: A National Practice Patterns Analysis.

BACKGROUND: Variation in the use of immunosuppression regimens after liver transplant has not been well described. METHODS: Immunosuppression regimens used after liver transplant were identified in a novel database integrating national transplant registry and pharmacy fill records for 24 238 recipients (2006-2014). Bilevel hierarchical models were developed to quantify the effects of transplant program, recipient, and donor characteristics on regimen choice. RESULTS: In the first 6 months after transplant, triple immunosuppression (tacrolimus, antimetabolite, corticosteroids) was the most common regimen (42.9%). By months 7 to 12, immunosuppression regimens were more commonly antimetabolite sparing (33.7%) or steroid sparing (26.9%), followed by triple (14.4%), mammalian target of rapamycin inhibitor (mTORi)-based (12.1%), or cyclosporine-based (9.2%). Based on intraclass correlation analysis, clinical characteristics explained less than 10% of the variation in immunosuppression choice, whereas program preference/practice explained 23% of steroid sparing, 26% of antimetabolite sparing, 28% of mTORi, and 21% of cyclosporine-based regimen use. Although case factors were not dominant practice drivers, triple immunosuppression in months 7 to 12 was more common among retransplant recipients and those with prior acute rejection. Hepatocellular carcinoma as cause of liver failure (adjusted odds ratio [aOR], 2.15; P<0.001), cancer within 6 months (aOR, 6.07; P<0.001), and 6-month estimated glomerular filtration rate less than 30 mL/min per 1.3 m2 (aOR, 1.98; P<0.001) were associated with mTORi use compared with triple immunosuppression in months 7 to 12, whereas acute rejection predicted lower use (aOR, 0.72; P=0.003). CONCLUSIONS: Liver transplant immunosuppression is dominantly driven by program preference, but case factors also affect regimen choice. This variation frames a natural experiment for future evaluations of comparative efficacy.

Immunobiology in VCA.

Transplantation of vascularized composite tissue is a relatively new field that is an amalgamation of experience in solid organ transplantation and reconstructive plastic and orthopedic surgery. What is novel about the immunobiology of VCA is the addition of tissues with unique immunologic characteristics such as skin and vascularized bone, and the nature of VCA grafts, with direct exposure to the environment, and external forces of trauma. VCAs are distinguished from solid organ transplants by the requirement of rigorous physical therapy for optimal outcomes and the fact that these procedures are not lifesaving in most cases. In this review, we will discuss the immunobiology of these systems and how the interplay can result in pathology unique to VCA as well as provide potential targets for therapy.

Models and methods for analyzing DCE-MRI: a review.

PURPOSE: To present a review of most commonly used techniques to analyze dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), discusses their strengths and weaknesses, and outlines recent clinical applications of findings from these approaches. METHODS: DCE-MRI allows for noninvasive quantitative analysis of contrast agent (CA) transient in soft tissues. Thus, it is an important and well-established tool to reveal microvasculature and perfusion in various clinical applications. In the last three decades, a host of nonparametric and parametric models and methods have been developed in order to quantify the CA's perfusion into tissue and estimate perfusion-related parameters (indexes) from signal- or concentration-time curves. These indexes are widely used in various clinical applications for the detection, characterization, and therapy monitoring of different diseases. RESULTS: Promising theoretical findings and experimental results for the reviewed models and techniques in a variety of clinical applications suggest that DCE-MRI is a clinically relevant imaging modality, which can be used for early diagnosis of different diseases, such as breast and prostate cancer, renal rejection, and liver tumors. CONCLUSIONS: Both nonparametric and parametric approaches for DCE-MRI analysis possess the ability to quantify tissue perfusion.

High-Resolution Imaging Using the VisualSonics Vevo 2100 on Isolated, Perfused Porcine Kidneys on Mechanical Circulatory Support.

Despite many improvements in the field of renal transplantation, the key problem that persists is the lack of organs for all the patients who need kidneys. This problem continues despite the addition of extended criteria donors and donation after cardiac death. Compounding this issue is the high discard rate and there are no good means to truly predict renal function using current pretransplantation testing parameters. In an isolated renal perfusion model using porcine kidneys, we tested the proof of principle that a Vevo 2100 high-frequency high-resolution ultrasound system (Fujifilm VisualSonics, Inc., Toronto, Canada) could assess renal parenchymal perfusion and flow in the central renal vessels which could not assess by conventional ultrasound. Images and velocities were easily obtained during these studies. High-frequency ultrasound imaging may be a feasible and reproducible method for assessing renal parenchymal integrity and function pretransplantation. Further studies are required to determine the sensitivity and specificity of this approach in comparison with traditional renal biopsy pretransplantation with the goal of increasing the identification and use of donated kidneys for transplantation.

BK viral disease in renal transplantation.

PURPOSE OF REVIEW: BK virus is one of the most frequent causes of graft loss after renal transplantation, with BK virus-associated nephropathy occurring in roughly 8% of patients, and graft loss rates reported as high as 50%. This review is meant to highlight the literature on BK viral disease following renal transplantation published in the most recent year. RECENT FINDINGS: Prevention of BK virus-associated graft loss requires early diagnosis of BK viral replication, which is best achieved by screening for BK viral DNA in the blood. Screening intervals more frequently than the currently recommended 3 months appear to offer increased efficacy. Reduction in immunosuppression remains the mainstay for treatment of BK viral disease, with consideration given to antiviral drug therapy with leflunomide. Acute rejection may be minimized by a short course of intravenous immunoglobulin. Sirolimus appears to be a promising addition to the therapeutic armamentarium. For patients requiring re-transplantation after BK virus-associated graft loss, viral clearance from the bloodstream prior to re-transplantation should be achieved to attain optimal results. SUMMARY: BK virus is a major pathogen affecting renal allografts, although intensive surveillance and targeted dose reduction in immunosuppression with the consideration of additional antiviral drug therapy can minimize graft loss resulting from infection.

Multiple-dose pharmacokinetics and pharmacodynamics of N-acetylcysteine in patients with end-stage renal disease.

BACKGROUND AND OBJECTIVES: ESRD is associated with systemic oxidative stress, an important nontraditional risk factor for the development of cardiovascular disease. Since interventions aimed at reducing oxidative stress may be beneficial, we examined the pharmacokinetics and pharmacodynamics of the widely used antioxidant N-acetylcysteine (NAC) after oral administration in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twenty-four ESRD patients were randomly assigned to receive 600 or 1200 mg of sustained-release NAC orally every 12 hours for 14 days. Seven healthy control subjects received NAC 600 mg in the same manner. Blood samples were obtained on days 1 and 15 for determination of NAC pharmacokinetics and pharmacodynamics. RESULTS: Significant dose-related increases in NAC plasma concentrations were observed in ESRD patients with no change in total clearance; a doubling of the dose resulted in a 2-fold increase in NAC area under the plasma concentration-time curve (AUC). However, NAC clearance was reduced by 90% in ESRD, leading to a 7-fold larger AUC and 13-fold longer half-life compared with healthy control subjects. NAC administration resulted in a significant reduction in total homocysteine plasma concentrations in ESRD and healthy subjects, but had no effect on several other oxidative stress markers. CONCLUSIONS: These findings indicate that the total clearance of oral NAC is significantly reduced in ESRD patients, leading to marked increases in systemic exposure, and suggest that NAC may have a limited role in the chronic treatment of oxidative stress-related illness.

Effect of increasing dialysate flow rate on diffusive mass transfer of urea, phosphate and beta2-microglobulin during clinical haemodialysis.

BACKGROUND: Diffusive clearance depends on blood and dialysate flow rates and the overall mass transfer area coefficient (K(o)A) of the dialyzer. Although K(o)A should be constant for a given dialyzer, urea K(o)A has been reported to vary with dialysate flow rate possibly because of improvements in flow distribution. This study examined the dependence of K(o)A for urea, phosphate and ß(2)-microglobulin on dialysate flow rate in dialyzers containing undulating fibers to promote flow distribution and two different fiber packing densities. METHODS: Twelve stable haemodialysis patients underwent dialysis with four different dialyzers, each used with a blood flow rate of 400 mL/min and dialysate flow rates of 350, 500 and 800 mL/min. Clearances of urea, phosphate and ß(2)-microglobulin were measured and K(o)A values calculated. RESULTS: Clearances of urea and phosphate, but not ß(2)-microglobulin, increased significantly with increasing dialysate flow rate. However, increasing dialysate flow rate had no significant effect on K(o)A or K(o) for any of the three solutes examined, although K(o) for urea and phosphate increased significantly as the average flow velocity in the dialysate compartment increased. CONCLUSIONS: For dialyzers with features that promote good dialysate flow distribution, increasing dialysate flow rate beyond 600 mL/min at a blood flow rate of 400 mL/min is likely to have only a modest impact on dialyzer performance, limited to the theoretical increase predicted for a constant K(o)A.

Use of ultrafiltered dialysate is associated with improvements in haemodialysis-associated morbidity in patients treated with reused dialysers.

BACKGROUND: Morbidity in haemodialysis patients is associated with chronic inflammation. Microbiological contaminants derived from dialysate are thought to be one inflammatory stimulus and previous studies found that highly purified dialysate reduces inflammation and morbidity. These studies were performed in the absence of practices, such as dialyser reuse, that are potentially inflammatory. We tested the hypothesis that highly purified dialysate reduces inflammation and morbidity even in the presence of other inflammatory stimuli. METHODS: This was a prospective observational study. After obtaining baseline data on inflammation, oxidant stress, nutrition and anaemia correction with standard dialysate, 105 patients were switched to dialysate that was ultrafiltered at the point of use and follow-up data were collected at 3-month intervals for 12 months. RESULTS: Introduction of ultrafiltered dialysate did not significantly reduce inflammation, as assessed by plasma concentrations of C-reactive protein and interleukin-6 or oxidant stress, as assessed by plasma concentrations of protein carbonyls and protein-free sulphydryls. Neither did it improve anaemia correction, as assessed by plasma haemoglobin and erythropoietin dose. However, introduction of ultrafiltered dialysate was associated with a significant reduction in plasma beta(2)-microglobulin concentration and a significant improvement in nutritional status, assessed by plasma albumin concentration and creatinine generation rate as a marker of muscle mass. CONCLUSION: Use of ultrafiltered dialysate was associated with improvements in some measures of morbidity, such as plasma beta(2)-microglubulin and nutrition. These changes occurred in spite of the presence of inflammatory stimuli, such as dialyser reuse, and with no measurable reduction in inflammation and oxidant stress.

Water treatment for hemodialysis: ensuring patient safety.

Patient safety has become an important focus of the Institute of Medicine and the medical community. Although hemodialysis is a routine therapy, it is nonetheless a complex procedure where errors can occur. In particular, errors related to water quality can lead to patient injury and to increased medical costs. Using the Institute of Medicine report on errors in medicine as a basis, this article discusses previously published incidents of patient injury related to water quality in terms of the types of errors that occurred. Epidemiologic techniques provide a framework to identify, correct, and possibly avert these types of errors in the future. While the ultimate responsibility for ensuring water quality rests with the medical director of the hemodialysis unit, patient safety should be a concern of all members of the nephrology community.