Identifying Proliferative Hepatocellular Carcinoma at Pretreatment CT: Implications for Therapeutic Outcomes after Transarterial Chemoembolization.

Background Hepatocellular carcinomas (HCCs) can be divided into proliferative and nonproliferative types, which may have implications for outcomes after conventional transarterial chemoembolization (cTACE). Biopsy to identify proliferative HCC is not routinely performed before cTACE. Purpose To develop and validate a predictive model for identifying proliferative HCCs using CT imaging features and to compare therapeutic outcomes between predicted proliferative and nonproliferative HCCs after cTACE according to this model. Materials and Methods This retrospective multicenter study included adults with HCC who underwent liver resection or cTACE between August 2013 and December 2020. A CT-based predictive model for identifying proliferative HCCs was developed and externally validated in a cohort that underwent resection. Diagnostic performance was calculated for the model. Thereafter, patients in the cTACE cohort were stratified into groups with predicted proliferative or nonproliferative HCCs according to the model. The primary outcome was overall survival (OS), and the secondary outcomes were tumor response rate and progression-free survival (PFS). These were compared between the two groups with use of the χ2 test and the log-rank test. Results A total of 1194 patients (1021 men; mean age, 54 years ± 12 [SD]; median follow-up time, 29.1 months) were included. The predictive model, named the SMARS score, incorporated lobulated shape, mosaic architecture, α-fetoprotein levels, rim arterial phase hyperenhancement, and satellite lesions. The area under the receiver operating characteristic curve for the SMARS score was 0.83 for the training cohort and 0.80 for the validation cohort. According to the SMARS score, patients with predicted proliferative HCCs (n = 114) had lower tumor response rate (48% vs 71%; P < .001) and worse PFS (6.6 months vs 12.4 months; P < .001) and OS (14.4 months vs 38.7 months; P < .001) than those with nonproliferative HCCs (n = 263). Conclusion The predictive model demonstrated good performance for identifying proliferative HCCs. According to the SMARS score, patients with predicted proliferative HCCs have worse prognosis than those with predicted nonproliferative HCCs after cTACE. © RSNA, 2023 Supplemental material is available for this article.

An Integrated Liver Function, Systemic Inflammation, and Tumor Characteristic Score Predicts Prognosis in Hepatocellular Carcinoma After Curative Resection.

BACKGROUND: Several scoring systems are currently used to predict prognosis of hepatocellular carcinoma (HCC), but none of them integrates liver function, systemic inflammation, and tumor characteristics in a unified model. The current study aimed to develop and validate a novel prognostic score that integrates liver function, systemic inflammation, and tumor characteristics in a unified model to predict the prognosis of HCC after curative resection. METHODS: Patients with HCC who underwent curative liver resection were included in a training set (n = 1027). Multivariate Cox regression was performed to determine the risk factors for a poor prognosis. A prognostic score was developed by assigning points for risk factors in proportion to beta coefficients in a Cox multivariable model. Predictive performance and distinction ability of the prognostic score were further evaluated in two independent validation cohorts treated with either curative resection (n = 281) or transarterial chemoembolization (TACE) (n = 404) and compared with 16 other models. RESULTS: The prognostic predictive system, named the function-inflammation-burden-alpha-fetoprotein (FIBA) score, was derived by assigning points for six independent predictors including albumin, total bilirubin, lymphocyte count, diameter of the largest tumor, number of tumors, and alpha-fetoprotein (AFP). The FIBA score showed an outperformed predictive value compared with other systems in both training and validation cohorts by giving the highest C-index, likelihood ratio chi-square values, and Wald test values as well as the lowest Akaike information criterion. CONCLUSION: The FIBA score can be used to stratify HCC patients treated with curative resection. Meanwhile, the FIBA score performs well against other prognostic scoring systems and is potentially broadly applicable to a TACE-treated patient cohort.

Precision oncology for intrahepatic cholangiocarcinoma in clinical practice.

BACKGROUND: Advanced cholangiocarcinoma has a poor prognosis. Molecular targeted approaches have been proposed for patients after progression under first-line chemotherapy treatment. Here, molecular profiling of intrahepatic cholangiocarcinoma in combination with a comprehensive umbrella concept was applied in a real-world setting. METHODS: In total, 101 patients received molecular profiling and matched treatment based on interdisciplinary tumour board decisions in a tertiary care setting. Parallel DNA and RNA sequencing of formalin-fixed paraffin-embedded tumour tissue was performed using large panels. RESULTS: Genetic alterations were detected in 77% of patients and included gene fusions in 21 patients. The latter recurrently involved the FGFR2 and the NRG1 gene loci. The most commonly altered genes were BAP1, ARID1A, FGFR2, IDH1, CDKN2A, CDKN2B, PIK3CA, TP53, ATM, IDH2, BRAF, SMARCA4 and FGFR3. Molecular targets were detected in 59% of patients. Of these, 32% received targeted therapy. The most relevant reason for not initiating therapy was the deterioration of performance status. Patients receiving a molecular-matched therapy showed a significantly higher survival probability compared to patients receiving conventional chemotherapy only (HR: 2.059, 95% CI: 0.9817-4.320, P < 0.01). CONCLUSIONS: Molecular profiling can be successfully translated into clinical treatment of intrahepatic cholangiocarcinoma patients and is associated with prolonged survival of patients receiving a molecular-matched treatment.

Repeat liver resection for recurrent intrahepatic cholangiocarcinoma: meta-analysis.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare malignancy. The aim of this meta-analysis was to evaluate outcomes of repeat liver resection and non-surgical approaches for treatment of recurrent ICC. METHODS: PubMed, Embase, and Web of Science databases were searched from their inception until March 2021 for studies of patients with recurrent ICC. Studies not published in English were excluded. Two meta-analyses were performed: a single-arm meta-analysis of studies reporting pooled short- and long-term outcomes after repeat liver resection for recurrent ICC (meta-analysis A), and a meta-analysis of studies comparing 1-, 3-, and 5-year overall survival (OS) rates after repeat liver resection and non-surgical approaches for recurrent ICC (meta-analysis B). RESULTS: Of 543 articles retrieved in the search, 28 were eligible for inclusion. Twenty-four studies (390 patients) were included in meta-analysis A and nine studies (591 patients) in meta-analysis B. After repeat liver resection, 1-, 3-, and 5-year OS rates were 87 (95 per cent c.i. 81 to 91), 58 (48 to 68), and 39 (29 to 50) per cent respectively. The 1-, 3-, and 5-year OS rates were higher after repeat liver resection than without surgery: odds ratio 2.70 (95 per cent c.i. 1.28 to 5.68), 2.89 (1.15 to 7.27), and 5.91 (1.59, 21.90) respectively. CONCLUSION: Repeat liver resection is a suitable strategy for recurrent ICC in selected patients. It improves short- and long-term outcomes compared with non-surgical treatments.

Multimodal Repair of Renal Artery Aneurysm - 10-year Single Center Experience.

BACKGROUND: Renal artery aneurysm (RAA) is a rare disease with various treatment options in indicated patients. In the current survey, the 10-year experience in treatment of RAAs using different endovascular and surgical treatments depending on RAA characteristics is discussed. METHODS: All patients undergone RAA treatment via endovascular or surgical approaches at our center between January 2010 and December 2020 were enrolled. Patient demographics and peri-operative and late results were collected from a prospectively maintained database. RESULTS: Eleven patients with RAA underwent treatment as follows: 4 patients received endovascular approach, 4 patients underwent in-situ RAA repair, and kidney autotransplantations were carried out in 3 patients. In all three treatment groups, the first therapeutic attempt was successful and none of the patients underwent secondary intervention due to RAA. Kidney autotransplantation was associated with a higher blood loss and a longer time of procedure compared to that of endovascular approach and in-situ repair. In-hospital postoperative complications were reported in 5 patients, including renal pole perfusion defect, renal artery thrombosis, and urinary tract infection. No acute kidney organ loss was seen, but 1 patient suffered from chronic kidney loss due to renal artery occlusion. In 1 patient undergoing autotransplantation, ureter anastomosis was reported, which led to acute renal failure, and a surgical treatment with resection and reanastomosis of the ureter was necessary. Hypertension was not resolved after RAA repair in any of the patients with preoperative hypertension. CONCLUSIONS: RAA treatment selection depends on patient characteristics, anatomy, location, and arising branches of the aneurysm. In cases with complex anatomy, treatment strategy could not be just decided based on consensus guidelines, but a multidisciplinary team is required. Interventional therapies showed excellent results in non-complicated proximal aneurysms, especially regarding the length of hospital stay and postoperative morbidities. Open surgery is a complementary alternative in cases where minimally invasive therapy is not possible. Ex-situ repair with autotransplantation could be considered for anatomically complex distal aneurysms.

Therapeutic lymphography for persistent chyle leak after pancreatic surgery.

BACKGROUND: Chyle leak is a common complication following pancreatic surgery. After failure of conservative treatment, lymphography is one of the last therapeutic options. The objective of this study was to evaluate whether lymphography represents an effective treatment for severe chyle leak (International study Group on Pancreatic Surgery, grade C) after pancreatic surgery. METHODS: Patients with grade C chyle leak after pancreatic surgery who received transpedal or transnodal therapeutic lymphography between 2010 and 2020 were identified from a prospectively maintained database. Clinical success of the lymphography was evaluated according to percent decrease of drainage output after lymphography (>50% decrease = partial success; >85% decrease = complete success). RESULTS: Of the 48 patients undergoing lymphography, 23 had a clinically successful lymphography: 14 (29%) showed partial and 9 (19%) complete success. In 25 cases (52%) lymphography did not lead to a significant reduction of chyle leak. Successful lymphography was associated with earlier drain removal and hospital discharge [complete clinical success: 7.1 days (±4.1); partial clinical success: 12 days (±9.1), clinical failure: 19 days (±19) after lymphography; p = 0.006]. No serious adverse events were observed. CONCLUSION: Therapeutic lymphography is a feasible, safe, and effective option for treating grade C chyle leak after pancreatic surgery.

Integrated Liver Inflammatory Score Predicts the Therapeutic Outcome of Patients with Hepatocellular Carcinoma after Transarterial Chemoembolization.

PURPOSE: To evaluate the performance of the integrated liver inflammatory score (ILIS) in predicting survival in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization, and to compare ILIS to other prognostic scoring systems and inflammatory indices. MATERIALS AND METHODS: This study included 192 patients with unresectable HCC who underwent transarterial chemoembolization from 3 medical centers. The potential risk factors of the patients' overall survival (OS) were determined by multivariate Cox regression analysis. The predictive performances of ILIS in 1-, 2-, 3-, 4-, and 5-year survival were evaluated using receiver operating characteristic curves. The discriminatory power in the OS of ILIS and the other known scoring systems or inflammatory indices was determined by C-statistic. RESULTS: Multivariate regression analysis showed that high ILIS (P = .047), low lymphocyte count (P = .034), beyond up-to-seven criteria (P = .021), and nonresponse to the first transarterial chemoembolization session (P = .039) were risk factors for poor prognosis after transarterial chemoembolization. The predictive performances of ILIS for 1-, 2-, 3-, 4-, and 5-year survival were good, with area under the curve values of 0.627, 0.631, 0.621, 0.577, and 0.681, respectively. ILIS outperformed other standard scoring systems and inflammatory indices in predicting OS, with a C-statistic of 0.625. CONCLUSIONS: ILIS is a powerful prognostic index for predicting the survival of patients with HCC after transarterial chemoembolization, which suggests that ILIS before treatment should be considered during the patient evaluation process.

Portal vein arterialization as a salvage procedure in hepatopancreatobiliary surgery: a systematic review.

Background: Portal vein arterialization (PVA) is a possible option when hepatic artery reconstruction is impossible during liver resection. The aim of this study was to review the literature on the clinical application of PVA in hepatopancreatobiliary (HPB) surgery. Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched the PubMed, Embase and Web of Science databases until December 2019. Experimental (animal) studies, review articles and letters were excluded. Results: Twenty studies involving 57 patients were included. Cholangiocarcinoma was the most common indication for surgery (40 patients [74%]). An end-to-side anastomosis between a celiac trunk branch and the portal vein was the main PVA technique (35 patients [59%]). Portal hypertension was the most common longterm complication (12 patients [21%] after a mean of 4.1 mo). The median followup period was 12 (range 1-87) months. The 1-, 3- and 5-year survival rates were 64%, 27% and 20%, respectively. Conclusion: Portal vein arterialization can be considered as a rescue option to improve the outcome in patients with acute liver de-arterialization when arterial reconstruction is not possible. To prevent portal hypertension and liver injuries due to thrombosis or overarterialization, vessel calibre adjustment and timely closure of the anastomosis should be considered. Further prospective experimental and clinical studies are needed to investigate the potential of this procedure in patients whose liver is suddenly de-arterialized during HPB procedures.

Contexte: L'artérialisation de la veine porte (AVP) est une option envisageable lorsqu'il est impossible de reconstruire l'artère hépatique au moment d'une résection du foie. Le but de cette étude était de faire le point sur la littérature concernant l'application clinique de l'AVP en cours de chirurgie hépatopancréatobiliaire (HPB). Méthodes: Nous avons procédé à une revue systématique selon les directives PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Nous avons interrogé systématiquement les bases de données PubMed, Embase et Web of Science jusqu'à décembre 2019. Les études expérimentales (chez l'animal), les articles de synthèse et les lettres ont été exclus. Résultats: Vingt études regroupant 57 patients ont été incluses. Le cholangiocarcinome était la plus fréquente indication de la chirurgie (40 patients [74 %]). L'anastomose terminolatérale d'une branche du tronc cæliaque avec la veine porte a été la principale technique d'AVP (35 patients [59 %]). L'hypertension portale a été la plus fréquente complication (12 patients [21 %] après une moyenne de 4,1 mois). Le suivi médian a été de 12 mois (éventail, 1­87 mois). Les taux de survie moyens à 1, 3 et 5 ans ont été de 64 %, 27 % et 20 %, respectivement. Conclusion: L'artérialisation de la veine porte peut être considérée comme une option de dernier ressort pour améliorer l'état des patients victimes d'une désartérialisation hépatique aiguë lorsque la reconstruction artérielle est impossible. Pour prévenir l'hypertension portale et les lésions au foie dues à la thrombose ou à l'hyperartérialisation, il faut veiller à ajuster le calibre vasculaire et fermer rapidement l'anastomose. D'autres études expérimentales et cliniques prospectives s'imposent afin d'analyser le potentiel de cette intervention chez les patients dont le foie se trouve subitement désartérialisé durant une chirurgie HPB.

Outcome of Self-Expanding Metal Stents in the Treatment of Anastomotic Leaks After Ivor Lewis Esophagectomy.

BACKGROUND: Esophageal anastomotic leakages after Ivor Lewis esophagectomy are severe and life-threatening complications. We analyzed the outcome of using self-expanding metal stents (SEMS) in the treatment of postoperative leakage after esophagogastrostomy. METHODS: Seventy patients with esophageal anastomotic leakage after Ivor Lewis esophagectomy for esophageal cancer who had received SEMS treatment between January 2006 and December 2015 at our clinic were identified in this retrospective study. The patients were analyzed according to demographic characteristics, risk factors, leakage characteristics, stent characteristics, stent-related complications, sealing success rate and mortality. RESULTS: Over a 10-year period, 70 patients received SEMS as treatment for postoperative anastomotic leakage after esophagectomy. Technical success of esophageal stenting in anastomotic leakage was achieved in 50 out of 70 cases (71.4%). Sealing success rate was 70% (n = 49) with a median treatment of 28 days (range 7-87). In 20 patients (28.6%), stent-related complications, such as stenosis, dislocation, leakage persistence, perforation or esophagotracheal fistula occurred after the SEMS treatment. Sixty-one patients (87.1%) survived SEMS treatment of esophagogastric anastomotic leakage. Mean follow-up for all patients was 38 months (IQR 10-76), and no significant difference was found in a comparison of the long-term survival rate between patients with successful and unsuccessful SEMS treatment. CONCLUSIONS: The management of esophageal anastomotic leaks after Ivor Lewis esophagectomy with SEMS is effective, safe and technically feasible. Aggressive non-surgical management should be considered when developing a treatment plan for stenting.

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer.

PURPOSE: To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients. METHODS: From 2012 to 2016, 106 patients (median age 74 years, range 50-94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent 18F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy. Tumor stage (UICC8, 2017) was IA/B (T1a-c, 1-3 cm) in 86 patients (81%) and IIA (T2a/b, 3-5 cm) in 20 patients (19%). Depending on tumor localization, three different fractionation schedules were used: 3 fractions of 17Gy, 5 fractions of 11Gy, or 8 fractions of 7.5 Gy. Tracking was based on fiducial implants in 13 patients (12%) and on image guidance without markers in 88%. RESULTS: Median follow-up was 15 months (range 0.5-46 months). Acute side effects were mild (fatigue grade 1-2 in 20% and dyspnea grade 1-2 in 17%). Late effects were observed in 4 patients (4%): 3 patients developed pneumonitis requiring therapy (grade 2) and 1 patient suffered a rib fracture (grade 3). In total, 9/106 patients (8%) experienced a local recurrence, actuarial local control rates were 88% (95% confidence interval, CI, 80-96%) at 2 years and 77% (95%CI 56-98%) at 3 years. The median disease-free survival time was 27 months (95%CI 23-31 months). Overall survival was 77% (95%CI 65-85%) at 2 years and 56% (95%CI 39-73%) at 3 years. CONCLUSION: CyberKnife® lung SBRT which allows for real-time tumor tracking and risk-adapted fractionation achieves satisfactory local control and low toxicity rates in inoperable early-stage primary lung cancer patients.

Candida-reactive T cells for the diagnosis of invasive Candida infection of the lumbar vertebral spine.

Invasive Candida infection is the fourth most common bloodstream infection. Blood cultures are the current gold standard diagnostic method, however, false negatives remain a clinical challenge. We developed a new technique measuring Candida-reactive T cells as diagnostic read-out for invasive Candida infection. In a pilot study, we followed the treatment course of a patient with an invasive Candida infection of the lumbar vertebral spine. We present the case of a 56-year-old patient with HIV-associated Burkitt lymphoma who developed septic shock during chemotherapy-induced neutropenia. For the first time, we provide flow cytometry-based diagnostics with Candida-reactive T cells for invasive candidiasis with comprehensive MRI imaging. The Candida-reactive T cell assay has potential to complement current diagnostic assays for invasive Candida infection and thus to support targeted treatment.

Incidental Findings in Abdominal Dual-Energy Computed Tomography: Correlation Between True Noncontrast and Virtual Noncontrast Images Considering Renal and Liver Cysts and Adrenal Masses.

PURPOSE: To assess correlation between attenuation measurements of incidental findings in abdominal second generation dual-energy computed tomography (CT) on true noncontrast (TNC) and virtual noncontrast (VNC) images. MATERIALS AND METHODS: Sixty-three patients underwent arterial dual-energy CT (Somatom Definition Flash, Siemens; pitch factor, 0.75-1.0; gantry rotation time, 0.28 seconds) after endovascular aneurysm repair, consisting of a TNC single energy CT scan (collimation, 128 × 0.6 mm; 120 kVp) and a dual-energy arterial phase scan (collimation, 32 × 0.6 mm, 140 and 100 kVp; blended, 120 kVp data set). Attenuation measurements in Hounsfield units (HU) of liver parenchyma and incidental findings like renal and hepatic cysts and adrenal masses on TNC and VNC images were done by drawing regions of interest. Statistical analysis was performed by paired t test and Pearson correlation. RESULTS: Incidental findings were detected in 56 (89%) patients. There was excellent correlation for both renal (n = 40) and hepatic cysts (n = 12) as well as adrenal masses (n = 6) with a Pearson correlation of 0.896, 0.800, and 0.945, respectively, and mean attenuation values on TNC and VNC images of 10.6 HU ± 12.8 versus 5.1 HU ± 17.5 (attenuation value range from -8.8 to 59.1 HU vs -11.8 to 73.4 HU), 6.4 HU ± 5.8 versus 6.3 HU ± 4.6 (attenuation value range from 2.0 to 16.2 HU vs -3.0 to 15.9 HU), and 12.8 HU ± 11.2 versus 12.4 HU ± 10.2 (attenuation value range from -2.3 to 27.5 HU vs -2.2 to 23.6 HU), respectively. As proof of principle, liver parenchyma measurements also showed excellent correlation between TNC and VNC (n = 40) images with a Pearson correlation of 0.839 and mean attenuation values on TNC and VNC images of 47.2 HU ± 10.5 versus 43.8 HU ± 8.7 (attenuation value range from 21.9 to 60.2 HU vs 4.5 to 65.3 HU). CONCLUSIONS: In conclusion, attenuation measurements of incidental findings like renal cysts or adrenal masses on TNC and VNC images derived from second generation dual-energy CT scans show excellent correlation providing considerable dose savings, favorable for future application in clinical routine.

The neck shaft angle: CT reference values of 800 adult hips.

OBJECTIVE: A precise understanding of the radiological anatomy and biomechanics as well as reliable reference values of the hip are essential. The primary goal of this study was to provide reference values of the neck-shaft angle (NSA) for adult patients based on the analysis of rotation corrected computed tomography (CT) scans of 800 hips. The secondary aim was to compare these measurements with simulated anteroposterior roentgenograms of the pelvis. MATERIALS AND METHODS: Pelvic CT scans of 400 patients (54.3 years, range 18-100 years; 200 female) were reconstructed in the derotated coronal plane of the proximal femur and as CT-based simulated anteroposterior roentgenograms of the pelvis in the anterior pelvic plane. Femora were categorized as coxa vara (<120°), physiologic (≥120° to <135°), and coxa valga (≥135°). Intra- and inter-rater reliability were analyzed. RESULTS: Primary research question: Mean NSA for male adults was 129.6° (range 113.2°-148.2°; SD 5.9°) and 131.9° (range 107.1°-151.9°; SD 6.8°) for females in derotated coronal reconstructions. Age (p < 0.001 in both views) and sex influenced the NSA significantly (p = 0.002 and p < 0.001); no significant differences were found between sides (p = 0.722 and p = 0.955). Overall, an excellent reliability of repeated measurements of one or two observers was found (ICC 0.891-0.995). Secondary research question: NSA values measured in the simulated anteroposterior roentgenogram and the rotation corrected coronal reconstruction differed significantly (p < 0.001). CONCLUSIONS: While anteroposterior pelvis radiographs are susceptible to rotational errors, the coronal reconstruction of the proximal femur in the femoral neck plane allows the correct measurement of the NSA.

CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury.

The chemokine (C-X-C motif) receptor 4 (CXCR4) is expressed on native cardiomyocytes and can modulate isolated cardiomyocyte contractility. This study examines the role of CXCR4 in cardiomyocyte response to ischaemia-reperfusion (I/R) injury. Isolated adult rat ventricular cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) to simulate I/R injury. In response to H/R injury, the decrease in CXCR4 expression was associated with dysfunctional energy metabolism indicated by an increased adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratio. CXCR4-overexpressing cardiomyocytes were used to determine whether such overexpression (OE) can prevent bio-energetic disruption-associated cell death. CXCR4 OE was performed with adenoviral infection with CXCR4 encoding-gene or non-translated nucleotide sequence (Control). The increased CXCR4 expression was observed in cardiomyocytes post CXCR4-adenovirus transduction and this OE significantly reduced the cardiomyocyte contractility under basal conditions. Although the same extent of H/R-provoked cytosolic calcium overload was measured, the hydrogen peroxide-induced decay of mitochondrial membrane potential was suppressed in CXCR4 OE group compared with control group, and the mitochondrial swelling was significantly attenuated in CXCR4 group, implicating that CXCR4 OE prevents permeability transition pore opening exposure to overload calcium. Interestingly, this CXCR4-induced mitochondrial protective effect is associated with the enhanced signal transducer and activator of transcription 3 (expression in mitochondria. Consequently, in the presence of H/R, mitochondrial dysfunction was mitigated and cardiomyocyte death was decreased to 65% in the CXCR4 OE group as compared with the control group. I/R injury leads to the reduction in CXCR4 in cardiomyocytes associated with the dysfunctional energy metabolism, and CXCR4 OE can alleviate mitochondrial dysfunction to improve cardiomyocyte survival.

3D immersive patient simulators and their impact on learning success: a thematic review.

BACKGROUND: Immersive patient simulators (IPSs) combine the simulation of virtual patients with a three-dimensional (3D) environment and, thus, allow an illusionary immersion into a synthetic world, similar to computer games. Playful learning in a 3D environment is motivating and allows repetitive training and internalization of medical workflows (ie, procedural knowledge) without compromising real patients. The impact of this innovative educational concept on learning success requires review of feasibility and validity. OBJECTIVE: It was the aim of this paper to conduct a survey of all immersive patient simulators currently available. In addition, we address the question of whether the use of these simulators has an impact on knowledge gain by summarizing the existing validation studies. METHODS: A systematic literature search via PubMed was performed using predefined inclusion criteria (ie, virtual worlds, focus on education of medical students, validation testing) to identify all available simulators. Validation testing was defined as the primary end point. RESULTS: There are currently 13 immersive patient simulators available. Of these, 9 are Web-based simulators and represent feasibility studies. None of these simulators are used routinely for student education. The workstation-based simulators are commercially driven and show a higher quality in terms of graphical quality and/or data content. Out of the studies, 1 showed a positive correlation between simulated content and real content (ie, content validity). There was a positive correlation between the outcome of simulator training and alternative training methods (ie, concordance validity), and a positive coherence between measured outcome and future professional attitude and performance (ie, predictive validity). CONCLUSIONS: IPSs can promote learning and consolidation of procedural knowledge. The use of immersive patient simulators is still marginal, and technical and educational approaches are heterogeneous. Academic-driven IPSs could possibly enhance the content quality, improve the validity level, and make this educational concept accessible to all medical students.

Web-Based Immersive Virtual Patient Simulators: Positive Effect on Clinical Reasoning in Medical Education.

BACKGROUND: Clinical reasoning is based on the declarative and procedural knowledge of workflows in clinical medicine. Educational approaches such as problem-based learning or mannequin simulators support learning of procedural knowledge. Immersive patient simulators (IPSs) go one step further as they allow an illusionary immersion into a synthetic world. Students can freely navigate an avatar through a three-dimensional environment, interact with the virtual surroundings, and treat virtual patients. By playful learning with IPS, medical workflows can be repetitively trained and internalized. As there are only a few university-driven IPS with a profound amount of medical knowledge available, we developed a university-based IPS framework. Our simulator is free to use and combines a high degree of immersion with in-depth medical content. By adding disease-specific content modules, the simulator framework can be expanded depending on the curricular demands. However, these new educational tools compete with the traditional teaching OBJECTIVE: It was our aim to develop an educational content module that teaches clinical and therapeutic workflows in surgical oncology. Furthermore, we wanted to examine how the use of this module affects student performance. METHODS: The new module was based on the declarative and procedural learning targets of the official German medical examination regulations. The module was added to our custom-made IPS named ALICE (Artificial Learning Interface for Clinical Education). ALICE was evaluated on 62 third-year students. RESULTS: Students showed a high degree of motivation when using the simulator as most of them had fun using it. ALICE showed positive impact on clinical reasoning as there was a significant improvement in determining the correct therapy after using the simulator. ALICE positively impacted the rise in declarative knowledge as there was improvement in answering multiple-choice questions before and after simulator use. CONCLUSIONS: ALICE has a positive effect on knowledge gain and raises students' motivation. It is a suitable tool for supporting clinical education in the blended learning context.

Thoracic type Ia endoleak: direct percutaneous coil embolization of the aortic arch at the blood entry site after TEVAR and double-chimney stent-grafts.

OBJECTIVES: To introduce a novel percutaneous technique to stop blood entry at the lesser aortic arch curvature by coil embolisation in type Ia endoleak after TEVAR. METHODS: A 61-year-old Marfan patient presented with type Ia endoleak of the aortic arch and a growing aortic arch pseudoaneurysm after TEVAR. Multiple preceding operations and interventions made an endovascular approach unsuccessful. Direct percutaneous puncture of the aneurysmal sac would have cured the sign, but not the cause of blood entry at the lesser curvature of the aortic arch. Direct CT-guided percutaneous puncture of the blood entry site in the aortic arch with fluoroscopically guided coil embolisation using detachable extra-long coils was successfully performed. RESULTS: Three weeks after the intervention, the patient developed fever because of superinfection of the pseudoaneurysm. The blood cultures and CT-guided mediastinal aspirate were sterile. After intravenous administration of antibiotics, the fever disappeared and the patient recovered. Six-month follow-up showed permanent closure of the endoleak and a shrinking aneurysmal sac. CONCLUSIONS: Direct percutaneous puncture of the aortic arch at the blood entry site of a thoracic type Ia endoleak after TEVAR and double-chimney stent-grafts with coil embolisation of the wedge-shaped space between the lesser aortic curvature and the stent-graft is possible. KEY POINTS: Endoleaks after thoracic endovascular aortic repair are common in 15-30 %. Most endoleaks can be treated by endovascular means. Direct percutaneous endoleak repair is described as a bail-out option. Direct percutaneous aortic arch coil embolisation of type 1a endoleak is possible. Antibiotic prophylaxis should be administered case by case, considering individual risk factors.