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Due to the shortage of kidneys donated for transplantation, surgeons are forced to use the organs with an elevated risk of poor function or even failure. Although the existing methods for pre-transplant quality evaluation have been validated over decades in population cohort studies across the world, new methods are needed as long as delayed graft function or failure in a kidney transplant occurs. In this study, we explored the potential of utilizing photoacoustic (PA) imaging during normothermic machine perfusion (NMP) as a means of evaluating kidney quality. We closely monitored twenty-two porcine kidneys using 3D PA imaging during a two-hour NMP session. Based on biochemical analyses of perfusate and produced urine, the kidneys were categorized into ‘non-functional’ and ‘functional’ groups. Our primary focus was to quantify oxygenation (sO2) within the kidney cortical layer of depths 2 mm, 4 mm, and 6 mm using two-wavelength PA imaging. Next, receiver operating characteristic (ROC) analysis was performed to determine an optimal cortical layer depth and time point for the quantification of sO2 to discriminate between functional and non-functional organs. Finally, for each depth, we assessed the correlation between sO2 and creatinine clearance (CrCl), oxygen consumption (VO2), and renal blood flow (RBF). We found that hypoxia of the renal cortex is associated with poor renal function. In addition, the determination of sO2 within the 2 mm depth of the renal cortex after 30 min of NMP effectively distinguishes between functional and non-functional kidneys. The non-functional kidneys can be detected with the sensitivity and specificity of 80% and 85% respectively, using the cut-off point of sO2 < 39%. Oxygenation significantly correlates with RBF and VO2 in all kidneys. In functional kidneys, sO2 correlated with CrCl, which is not the case for non-functional kidneys. We concl, Biomechanical Engineering

Objectives: Normothermic machine perfusion (NMP) provides a platform for pre-transplant kidney quality assessment that is essential for the use of marginal donor kidneys. Laser speckle contrast imaging (LSCI) presents distinct advantages as a real-time and noncontact imaging technique for measuring microcirculation. In this study, we aimed to assess the value of LSCI in visualizing renal cortical perfusion and investigate the additional value of dual-side LSCI measurements compared to single aspect measurement during NMP. Methods: Porcine kidneys were obtained from a slaughterhouse and then underwent NMP. LSCI was used to measure one-sided cortical perfusion in the first 100 min of NMP. Thereafter, the inferior renal artery branch was occluded to induce partial ischemia and LSCI measurements on both ventral and dorsal sides were performed.Results: LSCI fluxes correlated linearly with the renal blood flow (R2 = 0.90, p < 0.001). After renal artery branch occlusion, absence of renal cortical perfusion could be visualized and semiquantified by LSCI. The overall ischemic area percentage of the ventral and dorsal sides was comparable (median interquartile range [IQR], 38 [24−43]% vs. 29 [17−46]%, p = 0.43), but heterogenous patterns between the two aspects were observed. There was a significant difference in oxygen consumption (mean ± standard deviation [SD], 2.57 ± 0.63 vs. 1.83 ± 0.49 mLO2/min/100 g, p < 0.001), urine output (median [IQR], 1.3 [1.1−1.7] vs. 0.8 [0.6−1.3] mL/min, p < 0.05), lactate dehydrogenase (mean ± SD, 768 ± 370 vs. 905 ± 401 U/L, p < 0.05) and AST (mean ± SD, 352 ± 285 vs. 462 ± 383 U/L, p < 0.01) before and after renal artery occlusion, while no significant difference was found in creatinine clearance, fractional excretion of sodium, total sodium reabsorption and histological damage. Conclusions:LSCI fluxes correlated linearly with

Objectives: Normothermic machine perfusion (NMP) provides a platform for pre-transplant kidney quality assessment that is essential for the use of marginal donor kidneys. Laser speckle contrast imaging (LSCI) presents distinct advantages as a real-time and noncontact imaging technique for measuring microcirculation. In this study, we aimed to assess the value of LSCI in visualizing renal cortical perfusion and investigate the additional value of dual-side LSCI measurements compared to single aspect measurement during NMP. Methods: Porcine kidneys were obtained from a slaughterhouse and then underwent NMP. LSCI was used to measure one-sided cortical perfusion in the first 100 min of NMP. Thereafter, the inferior renal artery branch was occluded to induce partial ischemia and LSCI measurements on both ventral and dorsal sides were performed. Results: LSCI fluxes correlated linearly with the renal blood flow (R2 = 0.90, p < 0.001). After renal artery branch occlusion, absence of renal cortical perfusion could be visualized and semiquantified by LSCI. The overall ischemic area percentage of the ventral and dorsal sides was comparable (median interquartile range [IQR], 38 [24−43]% vs. 29 [17−46]%, p = 0.43), but heterogenous patterns between the two aspects were observed. There was a significant difference in oxygen consumption (mean ± standard deviation [SD], 2.57 ± 0.63 vs. 1.83 ± 0.49 mLO2/min/100 g, p < 0.001), urine output (median [IQR], 1.3 [1.1−1.7] vs. 0.8 [0.6−1.3] mL/min, p < 0.05), lactate dehydrogenase (mean ± SD, 768 ± 370 vs. 905 ± 401 U/L, p < 0.05) and AST (mean ± SD, 352 ± 285 vs. 462 ± 383 U/L, p < 0.01) before and after renal artery occlusion, while no significant difference was found in creatinine clearance, fractional excretion of sodium, total sodium reabsorption and histological damage. Conclusions: LSCI fluxes correlated linearly with renal blood flow during NMP. Renal cortical microcirculation and absent pe, Medical Instruments & Bio-Inspired Technology

BACKGROUND: Quercetin is a flavonoid with reported antioxidant, anti-inflammatory and anti-aging effects, and may limit muscle wasting in cancer cachexia. OBJECTIVE: To investigate the effect of quercetin on muscle wasting in the murine C26 cancer-cachexia model and assess the feasibility of non-invasive micro-CT analysis of skeletal muscle. MATERIALS AND METHODS: Custom CRM(P) diets supplemented with 250 mg/kg quercetin (Q) were obtained. Thirty CD2F1 mice were equally randomized to non-tumor-bearing (NTB), C26 tumor-bearing (TB), TB + Q. All groups started their allocated diet and underwent hindlimb micro-CT. Bodyweight, food intake, and grip-strength were recorded periodically. After 21 days, repeat micro-CT was performed. Gastrocnemius (GCM) and tibialis anterior (TA) muscles were resected. mRNA expression of MuRF1, Atrogin-1, myogenin, and MyoD was determined. RESULTS: NTB and TB + Q gained 9.4% and 5.3% bodyweight respectively, TB lost 3.9%. Hind limb skeletal muscle volume remained stable for NTB and TB + Q, whereas TB decreased from 242.0 mm3 to 212.8 mm3. Mean GCM muscle weight was 175.2 mg (NTB), 171.3 mg (TB + Q) versus 125.5 mg (TB). A tendency towards decreased expression of atrogin-1 and MuRF1 was observed in TB + Q. CONCLUSION: Dietary quercetin supplementation limits bodyweight loss and muscle wasting in the C26-cancer-associated cachexia model.

Isolated limb perfusion (ILP) with melphalan and tumor necrosis factor (TNF)-α is used to treat bulky, locally advanced melanoma and sarcoma. However, TNF toxicity suggests a need for better-tolerated drugs. Cilengitide (EMD 121974), a novel cyclic inhibitor of alpha-V integrins, has both anti-angiogenic and direct anti-tumor effects and is a possible alternative to TNF in ILP. In this study, rats bearing a hind limb soft tissue sarcoma underwent ILP using different combinations of melphalan, TNF and cilengitide in the perfusate. Further groups had intra-peritoneal (i.p.) injections of cilengitide or saline 2 hr before and 3 hr after ILP. A 77% response rate (RR) was seen in animals treated i.p. with cilengitide and perfused with melphalan plus cilengitide. The RR was 85% in animals treated i.p. with cilengitide and ILP using melphalan plus both TNF and cilengitide. Both RRs were significantly greater than those seen with melphalan or cilengitide alone. Histopathology showed that high RRs were accompanied by disruption of tumor vascular endothelium and tumor necrosis. Compared with ILP using melphalan alone, the addition of cilengitide resulted in a three to sevenfold increase in melphalan concentration in tumor but not in muscle in the perfused limb. Supportive in vitro studies indicate that cilengitide both inhibits tumor cell attachment and increases endothelial permeability. Since cilengitide has low toxicity, these data suggest the agent is a good alternative to TNF in the ILP setting.