Search Results (266)

Background/Objectives: Static cold storage (SCS) remains the standard method of kidney preservation. As a referral transplant center, we frequently receive kidneys initially preserved with SCS and subsequently initiate prolonged hypothermic machine perfusion (HMP) to extend allocation time and optimize recipient matching. The clinical impact of this sequential preservation strategy remains incompletely defined. To compare outcomes between kidneys preserved with SCS followed by prolonged HMP (SCS+HMP) and SCS alone. Methods: This single-center retrospective study included 200 adult recipients of kidney transplants from brain-dead donors (67 SCS+HMP; 133 SCS). Outcomes were primary graft non-function (PNF), delayed graft function (DGF), patient and death-censored graft survival, and renal function over 24 months. Univariable and multivariable analyses identified predictors of DGF. Propensity score matching was performed to adjust for baseline imbalances. Results: In the SCS+HMP group, grafts underwent a median of 244 min of SCS followed by 1300 min of HMP, resulting in longer total cold ischemia time than SCS alone (1545 vs. 1104 min; p < 0.001). After matching, 51 pairs (n = 102) were analyzed. In the matched cohort, PNF occurred in 2 patients (3.9%) in the SCS+HMP group and 3 patients (5.9%) in the SCS group (p = 1.0). DGF occurred less frequently in the SCS+HMP group than in the SCS group (17.6% vs. 39.2%; p = 0.027). In multivariable Firth penalized logistic regression, HMP was independently associated with lower odds of DGF (OR 0.34; 95% CI 0.13–0.82). During the 24-month follow-up, patient survival, death-censored graft survival, and creatinine trajectories were comparable between groups. Conclusions: Sequential HMP after initial SCS enables extended preservation and was associated with a lower incidence of delayed graft function. This strategy does not compromise patient survival, death-censored graft survival, or renal function at 24 months. Full article

Background/Objectives: To assess the diagnostic performance of dynamic susceptibility contrast (DSC) perfusion MRI parameters and machine learning methods for differentiating intracranial dural metastases (IDMs) from meningiomas. Methods: This retrospective diagnostic accuracy study included 56 patients (mean age: 57.6 ± 11.2 years; 20 men) with dural-based intracranial lesions (65 lesions): 18 patients with IDM (27 lesions) and 38 patients with meningiomas (38 lesions). All patients underwent DSC perfusion MRI. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), diffusion metrics, and dynamic time–signal intensity curve parameters were extracted. Group comparisons were performed using nonparametric statistical tests. Machine learning models, including linear discriminant analysis (LDA), were developed using patient-level grouped nested cross-validation to avoid data leakage. Diagnostic performance was evaluated using out-of-fold receiver operating characteristic (ROC) analysis, calibration assessment, and clinically oriented thresholds prioritizing metastasis sensitivity. Results: rCBV_mean and rCBF_mean were significantly higher in meningiomas than in dural metastases (median rCBV_mean: 4.71 vs. 2.95; median rCBF_mean: 3.44 vs. 2.02; both p < 0.001). Diffusion metrics and dynamic perfusion parameters, including wash-in time, percentage signal recovery, and wash-out slope, did not differ significantly between groups (p > 0.05). Univariate ROC analysis demonstrated strong discrimination for both rCBF_mean (AUC: 0.82; 95% CI: 0.72, 0.90) and rCBV_mean (AUC: 0.82; 95% CI: 0.72, 0.91). An LDA model integrating rCBF_mean and rCBV_mean achieved an out-of-fold AUC of 0.81 (95% CI: 0.72, 0.89) and improved specificity (85%) at a fixed metastasis sensitivity of 85%. Conclusions: DSC perfusion MRI-derived rCBF and rCBV are robust biomarkers for differentiating IDMs from meningiomas. An interpretable machine learning model integrating these parameters improves diagnostic specificity while maintaining high sensitivity. Full article

The rapid expansion of digital technologies and artificial intelligence (AI) has profoundly transformed cardiovascular imaging, enabling more precise, efficient, and reproducible assessment of cardiac structure and function. This narrative review summarizes recent advances in AI-driven methods across echocardiography, cardiac computed tomography, cardiac magnetic resonance, and nuclear imaging, with emphasis on image acquisition, automated quantification, and diagnostic and prognostic interpretation. We reviewed contemporary literature describing machine-learning and deep-learning applications for image reconstruction, segmentation, radiomics, and multimodal data integration. Current evidence demonstrates that AI improves image quality, reduces acquisition and analysis time, and enables automated, highly reproducible measurements of chamber volumes, function, tissue characterization, coronary anatomy, and myocardial perfusion, while facilitating advanced pattern recognition for differential diagnosis and risk stratification. Furthermore, digital platforms support remote acquisition, tele-echocardiography, and AI-assisted training of non-expert operators. Despite these advances, challenges remain regarding external validation, generalizability across vendors and populations, explainability, data governance, and regulatory compliance. In conclusion, AI and digital technologies are reshaping cardiovascular imaging by enhancing accuracy, efficiency, and accessibility, but their safe and effective clinical integration requires robust multicenter validation, transparent reporting, and ethical-legal frameworks that ensure trust, equity, and accountability. Full article

Extrapulmonary tuberculosis (EPTB) is an infectious disease characterized by the invasion of Mycobacterium tuberculosis beyond the lungs. Diagnosis is frequently delayed due to nonspecific clinical presentations that vary by organ system, making diagnostic imaging essential for disease detection, characterization, and treatment monitoring. The objective of this review is to examine and summarize imaging-based approaches for the diagnostic evaluation of EPTB across multiple body systems, including the central nervous system, spine, cardiovascular system, lymphatic system, abdominal and hepatic organs, genitourinary tract, cutaneous and soft tissue, and other rare sites. While computed tomography, magnetic resonance imaging, positron emission tomography, and ultrasound are widely used in the evaluation of EPTB, their ability to provide a definitive diagnosis is often limited by nonspecific radiologic findings. Emerging techniques, including perfusion-weighted MRI, contrast-enhanced ultrasound, and machine learning, have been discussed, as they improve lesion characterization and EPTB differentiation. By organizing imaging findings according to affected organ systems, this review highlights both shared diagnostic challenges and site-specific patterns that can inform clinical suspicion. Together, these developments underscore the value of a multimodal, organ-specific imaging approach integrated with the clinical context to improve the recognition and management of EPTB. Full article

Cadaveric preservation is fundamental to medical education, research, and surgical training, offering unmatched understanding of human anatomy and tissue dynamics. Although formalin fixation facilitates extended specimen preservation, its toxicity, tissue rigidity, and disruption of molecular analysis have prompted the creation of safer, more biologically representative alternatives. This review delineates the progression of cadaveric preservation, spanning from classical formaldehyde-based techniques through transitional low-toxicity chemical approaches to emerging formaldehyde-free methodologies. We assess the composition, benefits, and drawbacks of each technique, emphasizing the integration with machine learning-guided perfusion, nanotechnology-enhanced polymers, and hybrid approaches that combine digital imaging, 3D scaffolds, and automated monitoring. We propose a decision-making framework that integrates preservation decisions with instructional goals, surgical simulation needs, and research priorities, while adhering to ethical and environmental standards. This thorough analysis combines classic and innovative methodologies to provide practical suggestions for institutions aiming to enhance cadaveric resources for future medical professionals. Full article

Background/Objectives: Females are generally more resistant to ischemia-related ferroptosis than males, due to differences in iron metabolism, antioxidant pathways, and sex hormone-mediated regulation of ferroptosis suppressors. This has not been systematically studied in a human donor liver model. To investigate the effect of sex on ferroptosis and oxidative stress pathways in non-utilized donor livers (NDLs), we assessed patterns of gene expression in NDLs under ex vivo normothermic machine perfusion (NMP). Methods: We utilized the PROTECT dual-circuit ex vivo NMP system to assess three male and two female NDLs undergoing 6 h NMP. Perfusate and tissue samples were collected at baseline and 6 h of NMP. Malondialdehyde (MDA) levels were quantified as biochemical markers of iron overload and lipid peroxidation, respectively. Ferroptosis-related gene expression was assessed using molecular assays. Comparisons between male and female NDLs were used to determine the influence of sex on ferroptosis and oxidative injury during NMP. Results: NMP was successfully performed on NDLs (n = 5) from three male (56.3 ± 5.7 years) and two female donors (46.5 ± 0.7 years, p = 0.15). The fold-change in the oxidative stress marker MDA was comparable between female (1.2 ± 0.6) and male (1.0 ± 0.4) NDLs after 6 h NMP (p = 0.76). All livers showed upregulation of ferroptosis-related genes (Hypoxia-inducible factor 1 alpha, Iron Responsive Binding Elements 2, Ribosomal Protein L8, Ferritin Heavy Chain 1, Acyl-CoA synthetase family member 2, ATP synthase membrane subunit c locus 3, Heme-oxygenase 1, NAD(P)H Quinone Dehydrogenase 1, Tetratricopeptide Repeat Domain 35, Nuclear Factor Erythroid 2 Related Factor 2). ACSF2 expression was significantly higher in female NDLs compared with males undergoing 6 h NMP (3.6 ± 3.0 vs. 1.0 ± 0.7-fold change, p = 0.04). There were no sex-based significant differences observed in the expression of other ferroptosis-related genes (HIF-1α, IREB2, RPL8, FTH-1, ATP5G3, HO-1, NQO1, TTC35, and NRF2) between male and female NDLs. No gene reached statistical significance after false-discovery-rate (FDR) correction. Conclusions: Normothermic machine perfusion of NDLs was feasible, and no sex-related differences were observed in MDA levels or most ferroptosis-related gene expression after 6 h. Although ACSF2 showed higher expression in female livers, this was not significant after multiple testing correction, highlighting the need for larger studies to explore sex-dependent ferroptosis signaling during liver preservation. Full article

White matter injury (WMI) and blood–brain barrier (BBB) disruption contribute to neurological and cognitive deficits in intracerebral hemorrhage (ICH), with no effective pharmacological treatments available. Puerarin, with anti-inflammatory, anti-apoptotic, and antioxidant properties, exhibits neuroprotective potential. Here, mice subjected to ICH were treated with puerarin for 14 days. Neurological function, cerebral perfusion, and BBB integrity were assessed using behavioral tests, laser speckle imaging, Evans blue assays, immunofluorescence, Western blotting, and MRI. Integrated transcriptomics, machine learning, network pharmacology, molecular docking, and dynamics simulations were used to identify key targets. Puerarin improved neurological outcomes, reduced BBB permeability, enhanced microvascular perfusion, and attenuated WMI. Twenty-six hub genes were identified, with PARP1 and AKT1 correlated with OLIG2 and MBP, enriched in the cGAS-STING and AKT1-mTOR pathways. Molecular simulations indicated stable puerarin–cGAS interactions, validated experimentally: puerarin suppressed cGAS-STING activation, reduced oligodendrocyte apoptosis, and promoted remyelination. These results provide new insights into ICH pathogenesis and support puerarin as a potential therapeutic agent for BBB disruption and WMI. Full article

Kidney transplantation remains the ultimate treatment option for patients with end-stage renal disease. However, the global shortage in donor kidneys, exacerbated by challenges such as ischemia–reperfusion injury (IRI), reduces renal graft viability and negatively impacts post-transplant outcomes. Static cold storage, the gold standard of organ preservation, reduces metabolic demand but increases the risk of cold-induced mitochondrial dysfunction and IRI, especially in marginal kidneys. The introduction of machine perfusion techniques allows renal grafts and other solid organ grafts to be preserved at a wider range of temperatures. Organ preservation temperatures play an important role in determining post-transplant outcomes in the transplantation of the kidney and other transplantable solid organs. Therefore, determining the optimal preservation temperature may help increase organ utilization by avoiding unnecessary graft discards and increasing the safe use of marginal organs. This review discusses the impact of various preservation temperatures and methods of preservation on post-transplant outcomes in renal grafts and other organ grafts. Drawing from preclinical, clinical, and meta-analytic studies, we compare hypothermic (0–4 °C), moderate hypothermic (10 °C), subnormothermic (20–32 °C), normothermic (35–37 °C), and subzero preservation strategies, and cellular and molecular changes that occur in renal grafts and other solid organ grafts during preservation at these temperatures. Overall, temperature-controlled machine perfusion outperforms static preservation of renal grafts and other solid organ grafts from marginal and deceased donors, potentially expanding donor pools and improving long-term graft survival, and suggests the need for future research to determine optimal preservation temperature for renal grafts and other solid organ grafts to improve viability and post-transplant outcomes. Full article

Background: Musculoskeletal disorders (MSDs) are highly prevalent among healthcare workers, particularly nurses, with reported prevalence rates ranging from 57% to 93%. Perfusionists are highly specialized healthcare professionals responsible for operating heart–lung machines during cardiac surgery. To date, the prevalence of MSDs in this professional group has not been systematically investigated. To address this gap, perfusionists in Germany were surveyed regarding MSDs. Methods: The German version of the Nordic Musculoskeletal Questionnaire (NMQ) was administered. Pearson’s correlation and chi-square tests were applied. Results: A total of 287 perfusionists (72 female, 215 male; age 42.6 ± 11.9 years, professional experience 13.5 ± 10.9 years) from 45 German cardiac centers participated. Overall, 86% reported MSDs, with the lower back (65.5%) and neck (58.9%) being the most frequently affected regions, and 4.5% to 36.6% in other body regions. Increasing age was significantly associated with a higher prevalence in six body regions, and greater professional experience was associated in five regions. Occupational risk factors previously identified in nursing are assumed to apply to perfusion practice. Conclusions: This study demonstrates a high prevalence of MSDs among perfusionists in Germany. These findings underscore the need for preventive measures, coping strategies, and further research to reduce work-related musculoskeletal strain among perfusionists. Full article

Many advantages have been reported with the use of machine perfusion (MP) to rescue extended criteria donor (ECD) grafts, improving both short- and long-term post-liver transplantation (LT) outcomes. Acute kidney injury (AKI) is a common post-LT complication associated with these grafts and may compromise patient outcomes and increase LT-related costs. The aim of the study was to analyze the incidence of AKI in recipients of MP-treated grafts compared with those receiving conventionally cold-stored (SCS) grafts, both before and after a propensity score matching (PSM). From a prospectively maintained database, LT recipients of MP-treated grafts were compared with SCS grafts transplanted in the same study period (January 2022–May 2025). PSM was performed based on donor risk index (DRI), macrosteatosis (≥ or <30%), and recipient NaMELD score using a 3:1 (MP vs. SCS) ratio. Of the 177 consecutive LTs, 30 were performed with MP-treated grafts (MP group) and 147 using SCS (SCS group). The MP group displayed more marginal characteristics: older age (72 vs. 62 years, p = 0.02), higher proportion of DCD (10% vs. 0, p = 0.04), and higher frequency of moderate steatosis (macro ≥ 30%, 10% vs. 2.7%, p = 0.09). AKI rates were similar between groups (63% vs. 45.6%, p = 0.16), as was the distribution across AKI stages. After PSM, donor and recipient characteristics were balanced, and AKI rates remained similar between groups (58.6% vs. 47.1%, p = 0.39). Donor diabetes and recipient age were independent predictors of AKI in multivariate analysis (donor diabetes OR 3.29, 95% CI 1.347–8.030; recipient age: OR 1.06, 95% CI 1.015–1.097, both p < 0.05). MCP-1 and TNF-α levels measured in the perfusate fluid within the first minutes of perfusion were positively correlated with post-LT creatinine peak (MCP-1, p = 0.00023, R = 0.58; TNF-α, p = 0.0004, R = 0.57). In conclusion, machine perfusion remains a valuable strategy for rescuing ECD liver grafts. In the current era—characterized by increasing use of machine-perfused grafts and extended criteria donors—recipients demonstrate postoperative renal outcomes comparable to those receiving conventionally preserved grafts. Full article

Vascularised composite allotransplantation (VCA) has an evolving role in the reconstruction of complex functional and aesthetic deficits non-amenable to autologous or implant-based reconstructive modalities. International applications of VCA span upper extremity, face, abdominal wall, uterus, and penile transplantation, with more than 300 procedures performed worldwide. Among these, abdominal wall transplantation has uniquely contributed to the development of the sentinel skin flap (SSF) concept, in which solid organ transplant patients undergo simultaneous transplantation of a solid organ and a donor-derived vascularised skin flap, with the skin component of the SSF being trialled internationally as a means of monitoring for rejection within the solid organ allograft. Despite growing clinical success, VCA continues to face substantial barriers to wider adoption. Acute rejection remains highly prevalent, affecting up to 89% of recipients, with significant morbidity linked to intensive systemic immunosuppression. Challenges are further amplified by the unique immunological heterogeneity of composite grafts, ethical concerns surrounding identity-linked tissues, and the lack of standardised outcomes reporting across VCA subtypes. Advances in machine perfusion technologies and emerging cellular and biomaterial-based immunomodulation strategies show promise in reducing immunosuppression burden and improving graft longevity. This review outlines the current state of VCA, including clinical applications, outcomes, and mechanistic insights from pre-clinical studies, while highlighting key ethical considerations and evolving regulatory frameworks. Future progress will depend on standardised reporting systems, improved donor–recipient matching, better understanding of ischemia–reperfusion injury, and the development of next-generation immunosuppressive/immuno-modulatory therapies. Collectively, these innovations position VCA as a rapidly advancing field with significant potential to redefine reconstructive and transplant surgery. Full article

Background: Solid organ transplantation (SOT) is a life-saving treatment for patients with end-stage diseases and/or organ failure. However, access to healthy organs is often limited by challenges in organ preservation. Furthermore, upon transplantation, ischemia–reperfusion injury (IRI) can lead to increased organ rejection or graft failures. The work presented aims to address both challenges using an innovative nanomedicine platform for simultaneous drug and oxygen delivery. In recent studies, resveratrol (RSV), a natural antioxidant, anti-inflammatory, and reactive oxygen species (ROS) scavenging agent, has been reported to protect against IRI by inhibiting ferroptosis. Here, we report the design, development, and scalable manufacturing of the first-in-class dual-function perfluorocarbon-nanoemulsion (PFC-NE) perfusate for simultaneous oxygen and antioxidant delivery, equipped with a near-infrared fluorescence (NIRF) reporter, longitudinal, non-invasive NIRF imaging of perfusate flow through organs/tissues during machine perfusion. Methods: A Quality-by-Design (QbD)-guided optimization was used to formulate a triphasic PFC-NE with 30% w/v perfluorooctyl bromide (PFOB). Drug-free perfluorocarbon nanoemulsions (DF-NEs) and RSV-loaded nanoemulsions (RSV-NEs) were produced at 250–1000 mL scales using M110S, LM20, and M110P microfluidizers. Colloidal attributes, fluorescence stability, drug loading, and RSV release were evaluated using DLS, NIRF imaging, and HPLC, respectively. PFC-NE oxygen loading and release kinetics were evaluated during perfusion through the BMI OrganBank^® machine with the MEDOS HILITE^® oxygenator and by controlled flow of oxygen. The in vitro antioxidant activity of RSV-NE was measured using the oxygen radical scavenging antioxidant capacity (ORAC) assay. The cytotoxicity and ferroptosis inhibition of RSV-NE were evaluated in RAW 264.7 macrophages. Results: PFC-NE batches maintained a consistent droplet size (90–110 nm) and low polydispersity index (<0.3) across all scales, with high reproducibility and >80% PFOB loading. Both DF-NE and RSV-NE maintained colloidal and fluorescence stability under centrifugation, serum exposure at body temperature, filtration, 3-month storage, and oxygenation. Furthermore, RSV-NE showed high drug loading and sustained release (63.37 ± 2.48% at day 5) compared with the rapid release observed in free RSV solution. In perfusion studies, the oxygenation capacity of PFC-NE consistently exceeded that of University of Wisconsin (UW) solution and demonstrated stable, linear gas responsiveness across flow rates and FiO₂ (fraction of inspired oxygen) inputs. RSV-NE displayed strong antioxidant activity and concentration-dependent inhibition of free radicals. RSV-NE maintained higher cell viability and prevented RAS-selective lethal compound 3 (RSL3)-induced ferroptosis in murine macrophages (macrophage cell line RAW 264.7), compared to the free RSV solution. Morphological and functional protection against RSL3-induced ferroptosis was confirmed microscopically. Conclusions: This study establishes a robust and scalable PFC-NE platform integrating antioxidant and oxygen delivery, along with NIRF-based non-invasive live monitoring of organ perfusion during machine-supported preservation. These combined features position PFC-NE as a promising next-generation acellular perfusate for preventing IRI and improving graft viability during ex vivo machine perfusion. Full article

Ischemia–reperfusion injury (IRI) is a mechanism based on inflammatory mediators’ release and activation of effectors of damage. Studies showed a correlation between cytokine, severity of damage, and post-operative outcomes. Ex situ perfusion may work as a platform for the treatment of IRI mechanisms, such as the removal of cytokines using cytokine adsorption (CA). We assessed the safety and benefits of an integrated CA during ex situ dual-oxygenated hypothermic (D-HOPE) and normothermic perfusion (NMP). During the period of July 2021–December 2023, 84 octogenarian liver grafts, suitable for transplantation, were considered: 12 were randomized to D-HOPE or NMP with or without CA (D-HOPE + CA, D-HOPE, NMP + CA, NMP groups, n = 3 each) and compared to 72 performed using grafts preserved in static cold storage (SCS). IL-1, IL-6, IL-10, and TNF-a perfusate concentrations were evaluated together with perfusion parameters and post-operative outcomes. Perfusion procedures were unaffected by CA integration. In NMP, cytokine levels were 10–40 times higher than in healthy subjects and 20–50 times higher than D-HOPE. Cytokines were removed both in D-HOPE and NMP, but the concentration-dependent mechanisms of action of CA led to more remarkable removal in NMP. IL-10 and TNF-a concentrations were significantly lower in NMP + CA than in NMP. The application of CA was associated with significantly higher arterial flows both in D-HOPE and NMP, and reduced neutrophil infiltration in NMP. No differences in post-operative outcomes were found among groups. In conclusion, cytokine adsorption during ex situ machine perfusion of liver grafts from elderly donors is safe and feasible and is associated with modulation of inflammatory mediators and perfusion dynamics. These findings are hypothesis-generating, and larger studies are required to determine the clinical impact of this strategy. Full article

Replantation of an amputated finger is a complex microsurgical procedure that is rarely attempted in low-resource settings due to limited infrastructure and expertise. We report a case of complete amputation of a finger in rural Kenya that was successfully replanted during a humanitarian surgical mission. A 28-year-old man sustained a severe crush avulsion agricultural machine injury resulting in the amputation of all ten digits; only one digit was deemed suitable for replantation. The replantation was performed under loupe and microscope magnification by a visiting specialist team in collaboration with local staff. Intraoperatively, bony fixation with Kirschner wires, extensor and flexor digitorum profundus tendon repair, arterial and venous anastomoses, and neurorrhaphy of the digital nerve were achieved. Postoperatively, the finger survived with adequate perfusion. At one-month follow-up, the replanted finger was viable with progressing wound healing and early joint motion; further rehabilitation was arranged to maximize functional recovery. This case, which is, to our knowledge, one of the first documented digital replantations in East Africa, illustrates that successful microsurgical limb salvage is feasible in a non-specialized hospital setting. Our experience underscores that, with proper planning, training, and teamwork, advanced reconstructive procedures like finger replantation can be safely carried out even in resource-constrained hospitals, offering patients in low-income regions outcomes previously achievable only in high-resource centers. Full article

Liver graft shortage remains a major limiting factor in contemporary liver transplantation, particularly in the setting of increasing waiting list pressure and constrained donor availability. While the biological quality of donor organs cannot be modified surgically, several operative strategies have been developed to optimize liver utilization and compensate for insufficient graft volume. These include split liver transplantation (SLT), dual-graft living donor liver transplantation (DGLT), auxiliary procedures, and selected multi-graft or hybrid configurations. This review provides an updated and structured overview of surgical concepts aimed at maximizing effective liver mass for transplantation. We discuss indications, technical considerations, and reported outcomes of split, dual, and combined graft approaches, with particular emphasis on graft-to-recipient weight ratio (GRWR), portal inflow modulation, and prevention of small-for-size syndrome. The role of machine perfusion technologies—including normothermic and hypothermic approaches—as enabling tools for graft assessment and safer utilization of partial grafts is also examined. Finally, we address ethical and logistical challenges associated with complex graft strategies and outline future directions in which advances in perfusion, graft assessment, and staged transplantation concepts may further refine patient selection and procedural safety. Collectively, these strategies represent complementary solutions for extending liver transplantation beyond conventional single-graft paradigms in highly selected settings. Full article