Validating the Concept of Mechanical Circulatory Support with a Rotary Blood Pump in the Inferior Vena Cava in an Ovine Fontan Model.

Right-sided mechanical support of the Fontan circulation by existing devices has been compounded by the cross-sectional design of vena cava anastomosis to both pulmonary arteries. Our purpose was to investigate whether increasing inferior vena cava (IVC) flow with a rotary blood pump in the IVC only in an ovine animal model of Fontan would lead to acceptable superior vena cava (SVC) pressure. To achieve this, a Fontan circulation was established in four female sheep by anastomosing the SVC to the main pulmonary artery (MPA) and by interposing a Dacron graft between the IVC and the MPA. A rotary blood pump was then introduced in the graft, and the effect of incremental flows was observed at increasing flow regimen. Additionally, to stimulate increased pulmonary resistance, the experience was repeated in each animal with the placement of a restrictive band on the MPA distally to the SVC and Dacron graft anastomosis. Circulatory support of IVC flow alone increased the systemic cardiac output significantly, both with and without banding, indicating the feasibility of mechanical support of the Fontan circulation by increasing the flow only in the inferior vena cava. The increase in SVC pressure remained within acceptable limits, indicating the potential effectiveness of this mode of support. The findings suggest that increasing the flow only in the inferior vena cava is a feasible method for mechanical support of the Fontan circulation, potentially leading to an increase in cardiac output with acceptable increases in superior vena cava pressure.

Molecular Pathways and Animal Models of Cardiomyopathies.

Cardiomyopathies are a heterogeneous group of disorders of the heart muscle that ultimately result in congestive heart failure. Rapid progress in genetics, molecular and cellular biology with breakthrough innovative genetic-engineering techniques, such as next-generation sequencing and multiomics platforms, stem cell reprogramming, as well as novel groundbreaking gene-editing systems over the past 25 years has greatly improved the understanding of pathogenic signaling pathways in inherited cardiomyopathies. This chapter will focus on intracellular and intercellular molecular signaling pathways that are activated by a genetic insult in cardiomyocytes to maintain tissue and organ level regulation and resultant cardiac remodeling in certain forms of cardiomyopathies. In addition, animal models of different clinical forms of human cardiomyopathies with their summaries of triggered key molecules and signaling pathways will be described.

Case Report: Transcatheter interventional procedure to innominate vein turn-down procedure for failing fontan circulation.

Fontan physiology creates a chronic state of decreased cardiac output and systemic venous congestion, leading to liver cirrhosis/malignancy, protein-losing enteropathy, chylothorax, or plastic bronchitis. Creating a fenestration improves cardiac output and relieves some venous congestion. The anatomic connection of the thoracic duct to the subclavian-jugular vein junction exposes the lymphatic system to systemic venous hypertension and could induce plastic bronchitis. To address this complication, two techniques have been developed. A surgical method that decompresses the thoracic duct by diverting the innominate vein to the atrium, and a percutaneous endovascular procedure that uses a covered stent to create an extravascular connection between the innominate vein and the left atrium. We report a novel variant transcatheter intervention of the innominate vein turn-down procedure without creating an extravascular connection in a 39-month-old patient with failing Fontan circulation complicated by plastic bronchitis and a 2-year post-intervention follow-up.

Coping Strategies of Failing International Medical Students in Two Chinese Universities: A Qualitative Study.

Phenomenon: China hosts a large number of international medical students from low-income countries, and some fail examinations in the early stage of the Bachelor of Medicine and Bachelor of Surgery (MBBS) program. Little is known about how failing international medical students cope to recover their academic performance. It would be beneficial to investigate the coping strategies they use to help them recover their academic performance and progress. Approach: Semi-structured interviews were conducted with 21 international medical students at two universities in China from September 2020 to January 2021. These students had passed make-up exams or re-sits and progressed academically. A thematic analysis approach was used to identify major themes in the interview data. Findings: After failing initial exams or re-sits, students were found to adopt seven coping strategies to help them pass future examinations and recover their academic performance: (i) increased help-seeking behaviors, (ii) improved learning motivation and attitudes, (iii) improved learning strategies, (iv) improved exam preparation, (v) utilization of library resources, (vi) enhanced time management, and (vii) enhanced English language skills. Of the seven strategies, seeking help from friends, peers, seniors, and teachers was the strategy reported most frequently. Insights: The results of this study provide insights into the coping strategies that international undergraduate medical students adopt to recover from poor academic performance in Chinese universities. Host institutions should recognize the resilience and agency of such students to make positive changes. Furthermore, institutional efforts should be made to develop contextualized intervention plans that stimulate students' learning motivation and encourage them to adopt self-help strategies by incorporating useful resources (e.g., help from peers, seniors, and teachers). Enrollment should integrate specific English language proficiency criteria, and interviews and entrance exams should be conducted. For some failing students, it may be necessary to provide academic remediation.

Does long-term follow-up and monitoring of primary shoulder arthroplasty identify failing implants requiring revision?

BACKGROUND: Published scoping review has identified evidence paucity related to long-term follow-up of shoulder arthroplasty. We aim to report effectiveness of elective primary shoulder arthroplasty surveillance in identifying failing implants requiring revision. METHODS: A prospective database recording shoulder arthroplasty and subsequent follow-up surveillance in a shoulder unit was analyzed. Shoulder arthroplasty was performed by 4 fellowship-trained shoulder surgeons for accepted elective indications including the use of anatomic arthroplasty in arthritic shoulders with intact rotator cuff and a reverse prosthesis being used in rotator cuff-deficient shoulders and rotator cuff-competent arthritic shoulders when deemed preferable by the treating surgeon. All shoulder arthroplasty implants used had achieved a minimum 7A Orthopaedic Data Evaluation Panel (ODEP) rating. The included shoulder arthroplasties were performed between May 1, 2004, and December 31, 2021, with minimum 1-year follow-up. Surveillance program involves specialist physiotherapist review at 1, 2, 3, 5, 8, 10, and 15 years postoperatively, including clinical examination, outcome scoring, and radiographs. Patient-initiated review occurred between time points if a patient requested assessment because of symptoms. Outcome measures include ratio of failing implants identified by surveillance and patient-initiated review, with number of surveillance reviews offered and proportion that identified a failing implant requiring revision calculated. RESULTS: A total of 1002 elective primary shoulder arthroplasty with minimum 1-year follow-up were performed (547 reverse total shoulder arthroplasty [rTSA], 234 anatomic total shoulder arthroplasty [aTSA], and 221 hemiarthroplasty [HA]). A total of 238 patients died prior to December 31, 2022, resulting in 4019 surveillance appointments offered. Thirty-eight prostheses required revision ≥1 year postoperatively (6 rTSA, 9 aTSA, and 23 HA), with surveillance identifying requirement in 53% (33% rTSA, 56% aTSA, and 57% HA) and patient-initiated review in 47%. Mean years from implantation to revision was 5.2 (2.7 rTSA, 3.6 aTSA, and 6.6 HA). Revision indications included rotator cuff failure (56% aTSR and 43% HA) and glenoid erosion (57% HA). CONCLUSION: This is the first series reporting effectiveness of shoulder arthroplasty surveillance in identifying implants requiring revision. Surveillance identified more than half of implants requiring revision, although only 0.5% of appointments identified revision requirement. Surveillance enrolment may influence patient-initiated review utilization; therefore, similar studies using only patient-initiated follow-up would help inform recommendations.

Staged Acclimatization in a Failing Fontan by AFR in AFR: Ever-Decreasing Circles.

We describe serial implantation of atrial flow regulator (AFR) devices in the Fontan fenestration of a 4-year-old patient. Initially, the fenestration size was decreased using a 6/5 AFR, resulting in improved saturations and hemodynamics. One year later, further improvement was achieved by placing a 4/10 AFR inside the original device. (Level of Difficulty: Advanced.).

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.

Failed in aging? Queering in living with dementia.

This article explored the ways in which living with dementia brings potentials to queer the concept of "successful aging" and associated notions of being human. Regarding the progressive development of dementia, it can be assumed that people affected, no matter how hard they try, will sooner or later fail to age successfully. They increasingly become a symbol of what is called the "fourth age" and are framed as an essentialized other. Based on statements of people with dementia, it will be examined to what extent the position on the outside enables people affected to abandon societal guiding ideals and undermine hegemonic-dominant notions of aging. It is shown how they develop life-affirming ways of being-in-the-world that run counter to the idea of the rational, autonomous, consistent, active, productive, and healthy human beings.

Thoracic lymphatic anomalies in patients with univentricular hearts: correlation of morphologic findings in isotropic T2-weighted MRI with the outcome after fontan palliation.

Objectives: In this study we examined the correlation between the extent of thoracic lymphatic anomalies in patients after surgical palliation by total cavopulmonary connection (TCPC) and their outcome in terms of clinical and laboratory parameters. Materials and methods: We prospectively examined 33 patients after TCPC with an isotropic heavily T2-weighted MRI sequence on a 3.0 T scanner. Examinations were performed after a solid meal, slice thickness of 0.6 mm, TR of 2400 ms, TE of 692 ms, FoV of 460 mm, covering thoracic and abdominal regions. Findings of the lymphatic system were correlated with clinical and laboratory parameters obtained at the annual routine check-up. Results: Eight patients (group 1) showed type 4 lymphatic abnormalities. Twentyfive patients (group 2) presented less severe anomalies (type 1-3). In the treadmill CPET, group 2 reached step 7.0;6.0/8.0 vs. 6.0;3.5/6.8 in group 1 (p = 0.006*) and a distance of 775;638/854 m vs. 513;315/661 m (p = 0.006*). In the laboratory examinations, group 2 showed significantly lower levels of AST, ALT and stool calprotectin as compared to group 1. There were no significant differences in NT-pro-BNP, total protein, IgG, lymphocytes or platelets, but trends. A history of ascites showed 5/8 patients in group 1 vs. 4/25 patients in group 2 (p = 0.02*), PLE occurred in 4/8 patient in group 1 vs. 1/25 patients in group 2 (p = 0.008*). Conclusion: In the long-term follow-up after TCPC, patients with severe thoracic and cervical lymphatic abnormalities showed restrictions in exercise capacity, higher liver enzymes and an increased rate of symptoms of imminent Fontan-failure such as ascites and PLE.

Challenges in the management of the kidney allograft: from decline to failure: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

In March 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a virtual Controversies Conference to address the important but rarely examined phase during which the kidney transplant is failing or has failed. In addition to discussing the definition of a failing allograft, 4 broad areas were considered in the context of a declining functioning graft: prognosis and kidney failure trajectory; immunosuppression strategies; management of medical and psychological complications, and patient factors; and choice of kidney replacement therapy or supportive care following graft loss. Identifying and paying special attention to individuals with failing allografts was felt to be important in order to prepare patients psychologically, manage immunosuppression, address complications, prepare for dialysis and/or retransplantation, and transition to supportive care. Accurate prognostication tools, although not yet widely available, were embraced as necessary to define allograft survival trajectories and the likelihood of allograft failure. The decision of whether to withdraw or continue immunosuppression after allograft failure was deemed to be based most appropriately on risk-benefit analysis and likelihood of retransplantation within a few months. Psychological preparation and support was identified as a critical factor in patient adjustment to graft failure, as was early communication. Several models of care were noted that enabled a medically supportive transition back to dialysis or retransplantation. Emphasis was placed on the importance of dialysis-access readiness before initiation of dialysis, in order to avoid use of central venous catheters. The centrality of the patient to all management decisions and discussions was deemed to be paramount. Patient "activation," which can be defined as engaged agency, was seen as the most effective way to achieve success. Unresolved controversies, gaps in knowledge, and areas for research were also stressed in the conference deliberations.

Laparoscopic surgery in a child with a failing Fontan circulation.

A child with early failure of a Fontan circulation was listed for cardiac transplantation and then developed a subhepatic abscess. Surgical drainage was deemed necessary after the failure of an attempted percutaneous procedure. Following a multidisciplinary discussion, a laparoscopic technique was chosen to optimise postoperative recovery. To our knowledge, the literature does not describe any case of laparoscopic surgery in a patient with a failing Fontan circulation. This case report highlights the physiological variations involved with this management strategy, discusses the implications and risks, and offers some recommendations.

Molecular Aspects Implicated in Dantrolene Selectivity with Respect to Ryanodine Receptor Isoforms.

Dantrolene is an intra-cellularly acting skeletal muscle relaxant used for the treatment of the rare genetic disorder, malignant hyperthermia (MH). In most cases, MH susceptibility is caused by dysfunction of the skeletal ryanodine receptor (RyR1) harboring one of nearly 230 single-point MH mutations. The therapeutic effect of dantrolene is the result of a direct inhibitory action on the RyR1 channel, thus suppressing aberrant Ca2+ release from the sarcoplasmic reticulum. Despite the almost identical dantrolene-binding sequence exits in all three mammalian RyR isoforms, dantrolene appears to be an isoform-selective inhibitor. Whereas RyR1 and RyR3 channels are competent to bind dantrolene, the RyR2 channel, predominantly expressed in the heart, is unresponsive. However, a large body of evidence suggests that the RyR2 channel becomes sensitive to dantrolene-mediated inhibition under certain pathological conditions. Although a consistent picture of the dantrolene effect emerges from in vivo studies, in vitro results are often contradictory. Hence, our goal in this perspective is to provide the best possible clues to the molecular mechanism of dantrolene's action on RyR isoforms by identifying and discussing potential sources of conflicting results, mainly coming from cell-free experiments. Moreover, we propose that, specifically in the case of the RyR2 channel, its phosphorylation could be implicated in acquiring the channel responsiveness to dantrolene inhibition, interpreting functional findings in the structural context.

Elucidating the impact of dental caries, pain and treatment on academic performance in children.

BACKGROUND: The evidence for the impact of oral health on academic performance is still unclear. AIM: To assess the impact of oral health conditions on poor academic performance in schoolchildren by including a range of clinical and self-reported OH measures in a modified cross-sectional study. DESIGN: This study was carried out on schoolchildren aged 12-14 years in Jazan, Saudi Arabia, using a stratified and randomised cluster sampling method. Clinical indices from oral screening and self-reported OH conditions and behaviours and school absence from the self-administered questionnaire were recorded a month before the school examination. Results of passing or failing the examination were obtained after the examination. Statistical associations were examined using bivariate and multiple logistic regressions. The oral health measures were categorised based on the types of conditions and briefly appraised. RESULTS: Measures of dental caries, dental pain, soft tissue problems, oral hygiene, tooth discolouration, tooth mobility and school absence due to dental pain were associated with greater odds of failing the examination (p < .05). Measures of dental treatment and absence due to dental visits were associated with lower odds of failing (p < .05). CONCLUSIONS: Dental caries with pain likely explains the poor academic performance of schoolchildren, whereas treatment has a protective effect.

Changes in pulmonary artery index and its relation to outcome after stage II palliation in patients with hypoplastic left heart syndrome.

OBJECTIVES: This study aimed to prove if pulmonary artery (PA) size influences survival and if an additional aortopulmonary shunt (APS) promotes left PA growth after bidirectional cavopulmonary shunt (BCPS) in patients with hypoplastic left heart syndrome. METHODS: The medical records of patients with hypoplastic left heart syndrome who underwent Norwood procedure and BCPS between 2007 and 2020 were reviewed. Right, left and total (right + left) PA indices were calculated according to Nakata and colleagues. RESULTS: A total of 158 patients were included in this study. The median age at Norwood and BCPS was 8 (7-11) days and 3.6 (3.1-4.6) months, respectively. There were 7 hospital deaths and 12 late deaths. Survival after BCPS was 90.3% at 1 year and 86.2% at 2 years. Total, right and left PA indices were 238 (195-316), 136 (101-185) and 102 (75-130) mm2/m2 at the time of BCPS, and they were 237 (198-284), 151 (123-186) and 86 (69-108) mm2/m2 at the time of Fontan. Left PA index decreased significantly between the time of BCPS and Fontan (P < 0.01). Nine patients needed partial takedown and additional APS due to failing BCPS, but the additional APS did not promote the PA growth significantly. CONCLUSIONS: Preoperative PA index did not affect the mortality after BCPS. The partial takedown and additional APS for failing BCPS were unable to improve left PA size.

CA125 como nuevo biomarcador en pacientes con circulación de Fontan / CA125: a new biomarker in patients with Fontan circulation

Introducción y objetivos Los pacientes con circulación de Fontan (CF) presentan una gran incidencia de complicaciones y ningún biomarcador estratifica el riesgo. El objetivo es analizar la asociación de biomarcadores con un perfil clínico de disfunción de la CF, incluyendo por primera vez el antígeno carbohidrato 125 (CA125), y proponer una estimación del riesgo basada en la combinación de biomarcadores. Métodos Estudio transversal de adultos con CF. Se consideró perfil clínico desfavorable el combinado de insuficiencia cardiaca, arritmias auriculares, fístulas venovenosas, enteropatía pierdeproteínas o bronquitis plástica. Se analizaron variables clínicas y analíticas, incluidos CA125, NT-proBNP, función renal y hepática y amplitud de distribución eritrocitaria (ADE). Se realizó un estudio univariado y multivariado de la relación de dichas complicaciones clínicas y curvas ROC para obtener puntos de corte. Resultados Se incluyó a 56 pacientes (media de edad, 27,4±7,8 años). El 34% tenía un perfil clínico desfavorable, con valores de CA125 significativamente mayores (30,1 frente a 12,6 UI/ml; p=0,001). LnCA125 (OR=5,1; IC95%, 1,2-22), ADE (OR=1,8; IC95%, 1,1-3.1) y FIB4 (OR=38; IC95%, 1,7-855) se asociaron con un perfil de disfunción clínica. Los puntos de corte fueron CA125 ≥ 20 U/ml, FIB4 ≥ 0,75 y ADE ≥ 14,5%, y la probabilidad de un perfil clínico desfavorable fue del 81% con 2 o más biomarcadores elevados. Conclusiones El aumento de CA125 se asocia con mayor prevalencia de complicaciones en pacientes con CF. Los valores de CA125 ≥ 20 U/ml, FIB4 ≥ 0,75 y ADE ≥ 14,5% identifican con alta probabilidad fracaso clínico de la CF. (AU)

Introduction and objectives Patients with Fontan circulation (FC) have a high incidence of clinical complications. However, no biomarker is able to accurately stratify risk. The aim of this study was to analyze the relationship between biomarkers and clinical complications, including carbohydrate antigen 125 (CA125) for the first time, and to propose a risk estimation based on a combination of biomarkers. Methods Cross-sectional study of patients with FC. The clinical endpoint was the combination of heart failure, atrial arrhythmias, veno-venous fistulae, protein-losing enteropathy, or plastic bronchitis. Demographic, clinical, and laboratory variables were analyzed, including CA125, NT-proBNP, renal and liver function, and red cell distribution width (RDW). We performed univariate and multivariate analyses of the relationship between these variables and the composite endpoint. Cutoff values were calculated by ROC curves. Results We included 56 patients (27.4±7.8 years). A total of 34% showed the composite endpoint, with significantly higher CA125 levels (30.1 IU/mL vs 12.6 IU/mL; P=.001). In the multivariate model, the biomarkers related to the endpoint were LnCA125 (OR, 5.1; 95%CI, 1.2-22), RDW (OR, 1.8; 95%CI, 1.1-3.1), and FIB4 (OR, 38, 95%CI, 1.7-855). The cutoff points were CA125 ≥ 20 U/mL, FIB4 ≥ 0.75, and RDW ≥ 14.5%, and the probability of the occurrence of the endpoint was 81% if ≥ 2 biomarkers were elevated. Conclusions CA125 elevation is associated with a higher prevalence of complications in patients with Fontan-type circulation. CA125 levels ≥ 20U/mL, FIB4 ≥ 0.75 and RDW ≥ 14.5% identify with a high probability the clinical failure of FC. (AU)

Ventricular assist device support for failing Glenn circulation: Impact of concomitant Fontan completion in select patients.

BACKGROUND: Ventricular assist device (VAD) support for failing Glenn circulation represents a unique challenge. METHODS: We conducted a retrospective review of clinical outcomes in patients with VAD support for failing Glenn circulation between 2010 and 2020 at a tertiary pediatric institution. RESULTS: Ten patients were included: INTERMACS profiles were 1 in 3 patients and 2 in 7 patients. The median age, weight, and body surface area were 3.2 years, 13.0 kg, and 0.5 m2, respectively. Seven patients (70%) were implanted with continuous-flow devices and 3 with para-corporeal devices. Nine patients (90%) received heart transplant, with a median support duration of 77 days. Four (67%) out of 6 patients supported with discharge-capable devices were managed as outpatients. Post-transplant survival was 100%, with a median (range) follow up duration of 3.5 (1.8-11.9) years. There were 3 neurologic complications in 3 patients (0.9 events per patient-year); 2 intraoperative events (fatal hypoxia and symptomatic embolic stroke) and 1 postoperative (asymptomatic subarachnoid hemorrhage). Pump thrombosis occurred in one patient (0.3 events per patient-year), requiring pump exchange at day 65. Five patients (50%) received concomitant Fontan completion (fenestrated in 1). The Fontan-upgraded patients (vs Glenn) tended to be larger (median (range): 15.9 (12.6-22.9) vs 9.1 (7.7-22.8) kg), older (4.7 (3.1-6.5) vs 1.1 (0.9-10.1) years) and had a higher PaO2/FiO2 ratio (192 (52-336) vs 76 (59-78) mm Hg) on postoperative day 1. CONCLUSION: Our experience suggests the feasibility of durable VAD support for failing Glenn circulation. Concomitant Fontan completion may be considered in select patients to improve oxygen delivery.

Classification of surgical causes of and approaches to the chronically failing ileoanal pouch.

BACKGROUND: Although there are various surgical causes of and therapeutic approaches to the chronically failing ileoanal pouch (PF), cases are often detailed without distinguishing the exact cause and corresponding treatment. The aim of our study was to classify causes of PF and corresponding surgical treatment options, and to establish efficacy of surgical approach per cause. METHODS: This retrospective study included all consecutive adult patients with chronic PF surgically treated at our tertiary hospital between July 2014 and March 2021. Patients were classified according to a proposed sub-classification for surgical related chronic PF. Results were reported accordingly. RESULTS: A total of 59 procedures were completed in 50 patients (64% male, median age 45 years [IQR 34.5-54.3]) for chronic PF. Most patients had refractory ulcerative colitis as indication for their restorative proctocolectomy (68%). All patients could be categorized according to the sub-classification. Reasons for chronic PF were septic complications (n = 25), pouch body complications (n = 12), outlet problems (n = 11), cuff problems (n = 8), retained rectum (n = 2), and inlet problems (n = 1). For these indications, 17 pouches were excised, 10 pouch reconstructions were performed, and 32 pouch revision procedures were performed. The various procedures had different complication rates. Technical success rates of redo surgery for the different causes varied from 0 to 100%, with a 75% success rate for septic causes. CONCLUSIONS: Our sub-classification for chronic PF and corresponding treatments is suitable for all included patients. Outcomes varied between causes and subsequent management. Chronic PF was predominantly caused by septic complications with redo surgery achieving a 75% technical success rate.

CA125: a new biomarker in patients with Fontan circulation.

INTRODUCTION AND OBJECTIVES: Patients with Fontan circulation (FC) have a high incidence of clinical complications. However, no biomarker is able to accurately stratify risk. The aim of this study was to analyze the relationship between biomarkers and clinical complications, including carbohydrate antigen 125 (CA125) for the first time, and to propose a risk estimation based on a combination of biomarkers. METHODS: Cross-sectional study of patients with FC. The clinical endpoint was the combination of heart failure, atrial arrhythmias, veno-venous fistulae, protein-losing enteropathy, or plastic bronchitis. Demographic, clinical, and laboratory variables were analyzed, including CA125, NT-proBNP, renal and liver function, and red cell distribution width (RDW). We performed univariate and multivariate analyses of the relationship between these variables and the composite endpoint. Cutoff values were calculated by ROC curves. RESULTS: We included 56 patients (27.4±7.8 years). A total of 34% showed the composite endpoint, with significantly higher CA125 levels (30.1 IU/mL vs 12.6 IU/mL; P=.001). In the multivariate model, the biomarkers related to the endpoint were LnCA125 (OR, 5.1; 95%CI, 1.2-22), RDW (OR, 1.8; 95%CI, 1.1-3.1), and FIB4 (OR, 38, 95%CI, 1.7-855). The cutoff points were CA125 ≥ 20 U/mL, FIB4 ≥ 0.75, and RDW ≥ 14.5%, and the probability of the occurrence of the endpoint was 81% if ≥ 2 biomarkers were elevated. CONCLUSIONS: CA125 elevation is associated with a higher prevalence of complications in patients with Fontan-type circulation. CA125 levels ≥ 20U/mL, FIB4 ≥ 0.75 and RDW ≥ 14.5% identify with a high probability the clinical failure of FC.

The Biological Connotation of the “Fire Failing to Warm Earth” Pathogenesis of Carcinoma Transformation of Colitis Based on “Metabolic-Immune Interaction” / 中医杂志

During the carcinoma transformation of colitis， the imbalance of “metabolic-immune interaction” resulted from abnormal energy and metabolic substrates flow and direction was the key process， which caused by intercellular metabolic competition. Based on traditional Chinese medicine （TCM） theory and clinical research， we found that “fire failing to warm earth” is the key pathogenesis of colon-cancer transformation. “Fire” was a synonym for TCM to understand the energy metabolism， combined modern medical research findings， we thought energy metabolism disorders was a microcosmic manifestation of the “fire decline”， while abnormal immune function was the biological basis of “earth deficiency”. The imbalance between “metabolism-immune interaction” and the “fire failing to warm earth” pathogenesis of colitis-cancer transformation demonstrated the different understanding of the same pathological mechanism between western medicine and TCM. For treatment， it could be effectivce to delay the transformation of colitis-cancer by synergistically regulated the energy metabolism - “replenish fire” and enhanced the immune function - “nourish earth”， which was called the methods of replenishing fire to nourish earth.