Donor-derived infections among Chinese donation after cardiac death liver recipients

AIM To investigate blood cultures of deceased donors and report the confirmed transmission of bacterial infection from donors to liver recipients.METHODS We retrospectively studied the results of blood cultures among our donation after cardiac death(DCD) donors and calculated the donor-derived bacterial infection rates among liver recipients. Study participants underwent liver transplantation between January 1, 2010 and February 1, 2017. The study involved a total of 67 recipients of liver grafts from 67 DCD donors. We extracted the data of donors' and patients' characteristics, culture results and clinical outcomes, especially the post-transplant complications in liver recipients, from electronic medical records. We analyzed the characteristics of the donors and the corresponding liver recipients with emphasis put on donor-derived infections.RESULTS Head trauma was the most common origin of death among our 67 DCD donors(46.3%). Blood taken prior to the procurement operation was cultured for 53 of the donors, with 17 episodes of bloodstream infections developing from 13 donors. The predominant organism isolated from the blood of donors was Gram-positive bacteria(70.6%). Only three(4.5%) of 67 liver recipients developed confirmed donor-derived bacterial infections,with two isolates of multidrug-resistant Klebsiella pneumoniae and one isolate of multidrug-resistant Enterobacter aerogenes. The liver recipients with donorderived infections showed relation to higher crude mortality and graft loss rates(33.3% each) within 3 mo post transplantation, as compared to those without donor-derived infections(9.4% and 4.7%, respectively). All three liver recipients received appropriate antimicrobial therapy.CONCLUSION Liver recipients have high occurrence of donor-derived infections. The liver recipients with donor-derived multidrug-resistant Enterobacteriaceae infections can have good outcome if appropriate antimicrobial therapy is given.

Tauroursodeoxycholic acid and 4-phenyl butyric acid alleviate endoplasmic reticulum stress and improve prognosis of donation after cardiac death liver transplantation in rats

BACKGROUND： Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum （ER） stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death （DCD） liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid （TUDCA） and 4-phenyl butyric acid （PBA）, on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS： Male Sprague-Dawley rats （8-10 weeks） were randomly divided into control group： liver grafts without warm ischemia were implanted; DCD group： warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups： based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days.RESULTS： Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation （P〈0.01, 0.01 and 0.05, respectively） and oxidative indices （P〈0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine）, more severe liver damage （P〈0.01） and up-regulated ER stress signal expressions （P〈0.01 for GRP78, phos-eIF2al, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12）. All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels （P〈0.05）, increased superoxide dismutase activities （P〈0.01）, alleviated liver damage （P〈0.01）, down-regulated ER stress signal expressions （P〈0.01） and improved postoperative survivals （P〈0.01）. CONCLUSIONS： ER stress was involved with DCD liver trans- plantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.

Pathological Characteristics of Liver Allografts from Donation after Brain Death Followed by Cardiac Death in Pigs

Donation after brain death followed by circulatory death （DBCD） is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs （25-30 kg） were allocated randomly into donation after brain death （DBD）, donation after circulatory death （DCD） and DBCD groups. Brain death was induced by aug- menting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were col- lected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [（0.56±0.30）%] and DBCD [（0.50 ±0.11）%] groups was much lower than that in DCD group [（3.78±0.33）%] （P〈0.05）. And there was no significant difference between DBD group and DBCD group （P〉0.05））. The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

Pre-participation screening for the prevention of sudden cardiac death in athletes

Pre-partecipation screening is the systematic practice of medically evaluating large populations of athletes before participation in sport activities for the purpose of identifying abnormalities that could cause disease progression or sudden death.In order to prevent sudden cardiac death(SCD),cardiovascular screening should include a strategy for excluding high-risk subjects from athletic and vigorous exercise.There are two major screening programmes in the world.In the United States competitive athletes are screened by means of family and personal history and physical examination.In Italy there is a mandatory screening for competitive athletes,which includes a resting electrocardiogram(ECG)for the detection of cardiac abnormalities.The most important issue to be addressed is whether a screened subject is really guaranteed that she/he is not suffering from any cardiac disease or at risk for SCD.Conceivably,the introduction of echocardiogram during the pre-participation screening,could be reasonable,despite the discrete sensitivity of ECG,in raising clinical suspicions of severe cardiac alterations predisposing to SCD.It is clear that the costbenefit ratio per saved lives of the ECG screening is abenchmark of the Public Health policy.On the contrary,the additional introduction of echocardiography in a large population screening programme seems to be too much expansive for the Public Health and for this reason not easily practicable,even if useful and not invasive.Even if we strongly believe that a saved life is more important than any cost-efficacy evaluation,the issue of the economical impact of this approach should be further assessed.

Sudden cardiac death in a case of Crohn's disease with COVID-19: A case report

Rationale:The mechanism of sudden cardiac death in COVID-19 can be multifactorial.Cardiac hypersensitivity to 5-ASA therapy leading to myocarditis has been reported in some cases.Cytokine storm syndrome and idiosyncratic reaction with mesalazine use may lead to sudden cardiac death in COVID-19.Use of immunosuppressants in hospitalized COVID-19 patients should be continued with caution,especially in patients with inflammatory bowel disease.Patient’s concern:A 75-year-old man who was tested positive for SARS-CoV-2 was admitted with a history of shortness of breath for the last two days.He was a known case of Crohn’s disease treated with mesalazine.Diagnosis:COVID-19 pneumonia with underlying Crohn’s disease leading to sudden cardiac death.Intervention:Remdesivir,antibiotics,steroids,low molecular weight heparin,tablet zinc,tab vitamin C,and other supportive treatment were started.Because of increased inflammatory markers,itolizumab was given to the patient on the 2nd day.Outcome:On the 5th day of the intensive care unit,the patient complained of sudden chest pain with respiratory distress leading to bradycardia and asystole and could not be resuscitated.Lessons:Causes for sudden cardiac death in COVID-19 pneumonia patients with Crohn’s disease is multifactorial.Although mesalazine may be a safe and effective drug in the management of inflammatory bowel disease,it can induce sytokine strom syndrome and idiosyncratic reactions that could be one of the reasons of sudden cardic death.Therefore,we should be aware of its serious and potentially life-threatening complications,especially in COVID-19 infected patients.

Uric acid is associated with cardiac death in patients with hypertrophic obstructive cardiomyopathy

BACKGROUND The role of uric acid(UA) in survival of patients with hypertrophic obstructive cardiomyopathy(HOCM) has not been fully evaluated. This study aimed to determine whether UA could be an independent risk factor of cardiac death in patients with HOCM.METHODS A total of 317 patients with HOCM, who were receiving conservative treatment in Fuwai Hospital from October2009 to December 2014, all of them completed UA evaluations, were analyzed. Patients were divided into three groups according to the UA levels: Tertile 1(≤ 318 μmol/L, n = 106), Tertile 2(319 to 397 μmol/L, n = 105), and Tertile 3(≥ 398 μmol/L, n = 106).RESULTS During a median follow-up of 45 months, 29 cardiac deaths(9.1%) occurred, including 6 sudden cardiac deaths and23 heart failure-related deaths. Cardiac death in Tertile 3(n = 16, 55.2%) was significantly higher than in Tertile 1(n = 6, 20.7%)and Tertile 2(n = 7, 24.1%). In univariate model, UA level(continuous value) showed predictive value of cardiac death [hazard ratio(HR) = 1.006, 95% CI: 1.003-1.009, P = 0.009]. Univariate Cox survival analysis had shown a significant higher property of cardiac death in patients of Tertile 3 when compared with those of Tertile 1, but cardiac death in patients of Tertile 2 did not show significant prognositic value compared with those of Tertile 1(HR = 3.927, 95% CI: 0.666-23.162, P = 0.131). UA was found to be an independent risk factor(HR = 1.005, 95% CI: 1.001-1.009, P = 0.009) of cardiac death in the multivariate regression analysis after the adjustment for age, body mass index, atrial fibrillation, hemoglobin, creatinine, high-sensitivity C-reactive protein, interventricular septum/left ventricular posterior wall ratio, left ventricular outflow tract and left ventricular ejection fraction.CONCLUSIONS UA concentration was found to be independently associated with cardiac death in HOCM patients receiving conservative treatment. Randomized trials of UA-lowering agents for HOCM patients are warranted.

Early repolarization syndrome: A cause of sudden cardiac death

Early repolarization syndrome(ERS), demonstrated as J-point elevation on an electrocardiograph, was formerly thought to be a benign entity, but the recent studies have demonstrated that it can be linked to a considerable risk of life- threatening arrhythmias and sudden cardiac death(SCD). Early repolarization characteristics associated with SCD include high-amplitude J-point elevation, horizontal and/or downslopping ST segments, and inferior and/or lateral leads location. The prevalence of ERS varies between 3% and 24%, depending on age, sex and J-point elevation(0.05 m V vs 0.1 m V) being the main determinants.ERS patients are sporadic and they are at a higher risk of having recurrent cardiac events. Implantable cardioverter-defibrillator implantation and isoproterenol are the suggested therapies in this set of patients. On the other hand, asymptomatic patients with ERS are common and have a better prognosis. The risk stratification in asymptomatic patients with ERS still remains a grey area. This review provides an outline of the up-to-date evidence associated with ERS and the risk of life- threatening arrhythmias. Further prospective studies are required to elucidate the mechanisms of ventricular arrhythmogenesis in patients with ERS.

Risk factors for sudden cardiac death to determine high risk patients in specific patient populations that may benefit from a wearable defibrillator

BACKGROUND There is a high risk for sudden cardiac death(SCD) in certain patient groups that would not meet criteria for implantable cardioverter defibrillator(ICD) therapy.In conditions such as hypertrophic cardiomyopathy(HCM) there are clear risk scores that help define patients who are high risk for SCD and would benefit from ICD therapy. There are however many areas of uncertainty such as certain patients post myocardial infarction(MI). These patients are high risk for SCD but there is no clear tool for risk stratifying such patients.AIM To assess risk factors for sudden cardiac death in major cardiac disorders and to help select patients who might benefit from Wearable cardiac defibrillators(WCD).METHODS A literature search was performed looking for risk factors for SCD in patients post-MI, patients with left ventricular systolic dysfunction(LVSD), HCM, long QT syndrome(LQTS). There were 41 studies included and risk factors and the relative risks for SCD were compiled in table form.RESULTS We extracted data on relative risk for SCD of specific variables such as age,gender, ejection fraction. The greatest risk factors for SCD in post MI patients was the presence of diabetes [Hazard ratio(HR) 1.90-3.80], in patient with LVSD was ventricular tachycardia(Relative risk 3.50), in LQTS was a prolonged QTc(HR36.53) and in patients with HCM was LVH greater than 20 mm(HR 3.10). A proportion of patients currently not suitable for ICD might benefit from a WCDCONCLUSION There is a very high risk of SCD post MI, in patients with LVSD, HCM and LQTS even in those who do not meet criteria for ICD implantation. These patients may be candidates for a WCD. The development of more sensitive risk calculators to predict SCD is necessary in these patients to help guide treatment.

Warm ischemia time and elevated serum uric acid are associated with metabolic syndrome after liver transplantation with donation after cardiac death

AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre-and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-Ⅲ criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147(13.6%). Recipient's body mass index(P = 0.024), warm ischemia time(WIT)(P = 0.045), and posttransplant hyperuricemia(P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients(P < 0.001). After the 1 s t mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.

Developing a donation after cardiac death risk index for adult and pediatric liver transplantation

AIM To identify objective predictive factors for donor after cardiac death(DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index(DCD-RI) to help in prospective decision making on organ use.METHODS The model included objective data from a single institute DCD database(2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated.RESULTS DCD graft survival predictors were primary indication for transplant(P = 0.066), retransplantation(P = 0.176), MELD > 25(P = 0.05), cold ischemia > 10 h(P = 0.292) and donor hepatectomy time > 60 min(P = 0.028).According to the calculated DCD-RI score three risk classes could be defined of low(DCD-RI < 1), standard(DCD-RI 2-4) and high risk(DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively.CONCLUSION The DCD-RI score independently predicted graft loss(P < 0.001) and the DCD-RI class predicted graft survival(P < 0.001).

Hypertrophic cardiomyopathy and sudden cardiac death

Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease that affects the left ventricle. HCM can appear at any age, with the majority of the patients remaining clinically stable. When patients complain of symptoms, these include: dyspnea, dizziness, syncope and angina. HCM can lead to sudden cardiac death (SCD), mainly due to ventricular tachyarrhythmia or ventricular tachycardia. High-risk patients benefit from implantable cardioverter-defibrillators. Left ventricular outflow tract obstruction is not a rare feature in HCM, especially in symptomatic patients, and procedures that abolish that obstruction provide positive and consistent results that can improve longterm survival. HCM is the most common cause of sudden death in young competitive athletes and preparticipation screening programs have to be implemented to avoid these tragic fatalities. The structure of these programs is a matter of large debate. Worldwide registries are necessary to identify the full extent of HCMrelated SCD.

Kidney donation after cardiac death

There is continuing disparity between demand for and supply of kidneys for transplantation. This review describes the current state of kidney donation after cardiac death(DCD) and provides recommendations for a way forward. The conversion rate for potential DCD donors varies from 40%-80%. Compared to controlled DCD, uncontrolled DCD is more labour intensive, has a lower conversion rate and a higher discard rate. The super-rapid laparotomy technique involving direct aortic cannulation is preferred over in situ perfusion in controlled DCD donation and is associated with lower kidney discard rates, shorter warm ischaemia times and higher graft survival rates. DCD kidneys showed a 5.73-fold increase in the incidence of delayed graft function(DGF) and a higher primary non function rate compared to donation after brain death kidneys, but the long term graft function is equivalent between the two. The cold ischaemia time is a controllable factor that significantly influences the outcome of allografts, for example, limiting it to < 12 h markedly reduces DGF. DCD kidneys from donors < 50 function like standard criteria kidneys and should be viewed as such. As the majority of DCD kidneys are from controlled donation, incorporation of uncontrolled donation will expand the donor pool. Efforts to maximise the supply of kidneys from DCD include: implementing organ recovery from emergency department setting; improving familyconsent rate; utilising technological developments to optimise organs either prior to recovery from donors or during storage; improving organ allocation to ensure best utility; and improving viability testing to reduce primary non function.

Potential approaches to improve the outcomes of donation after cardiac death liver grafts

There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death(DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications. In order to maximize the usage of DCD livers several new preservation approaches have been proposed. Here, we will review 3 innovative organ preservation methods:(1) different ex vivo perfusion techniques;(2) persufflation with oxygen; and(3) addition of thrombolytic therapy. Improvement of the quality of DCD liver grafts could increase the pool of liver graft's for transplantation, improve the outcomes, and decrease the mortality on the waiting list.

Electrophysiologic testing guided risk stratification approach for sudden cardiac death beyond the left ventricular ejection fraction

Sudden cardiac death threats ischaemic and dilated cardiomyopathy patients. Anti- arrhythmic protection may be provided to these patients with implanted cardiac defibrillators(ICD), after an efficient risk stratification approach. The proposed risk stratifier of an impaired left ventricular ejection fraction has limited sensitivity meaning that a significant number of victims will remain undetectable by this risk stratification approach because they have a preserved left ventricular systolic function. Current risk stratification strategies focus on combinations of non invasive methods like T wave alternans, late potentials, heart rate turbulence, deceleration capacity and others, with invasive methods like the electrophysiologic study. In the presence of an electrically impaired substrate with formed post myocardial infarction fibrotic zones, programmed ventricular stimulation provides important prognostic information for the selection of the patients expected to benefit from an ICD implantation, while due to its high negative predictive value, patients at low risk level may also be detected. Clustering evidence from different research groups and electrophysiologic labs support an electrophysiologic testing guided risk stratification approach for sudden cardiac death.

Early detection of sudden cardiac death by using classical linear techniques and time-frequency methods on electrocardiogram signals

Early detection of sudden cardiac death may be used for surviving the life of cardiac patients. In this paper we have investigated an algorithm to detect and predict sudden cardiac death, by processing of heart rate variability signal through the classical and time-frequency methods. At first, one minute of ECG signals, just before the cardiac death event are extracted and used to compute heart rate variability (HRV) signal. Five features in time domain and four features in frequency domain are extracted from the HRV signal and used as classical linear features. Then the Wigner Ville transform is applied to the HRV signal, and 11 extra features in the time-frequency (TF) domain are obtained. In order to improve the performance of classification, the principal component analysis (PCA) is applied to the obtained features vector. Finally a neural network classifier is applied to the reduced features. The obtained results show that the TF method can classify normal and SCD subjects, more efficiently than the classical methods. A MIT-BIH ECG database was used to evaluate the proposed method. The proposed method was implemented using MLP classifier and had 74.36% and 99.16% correct detection rate (accuracy) for classical features and TF method, respectively. Also, the accuracy of the KNN classifier were 73.87% and 96.04%.

Ventricular Arrhythmia-Free Survival Following Therapeutic Hypothermia in Patients with Sudden Cardiac Death Due to Ventricular Tachycardia or Fibrillation

Background: The potential benefits of implantable cardioverter-defibrillator (ICD) therapy in patients with sudden cardiac death (SCD) treated with therapeutic hypothermia (TH) have not been well studied. Methods: Incidence of recurrent non-sustained ventricular arrhythmia, ICD therapy, and death were ascertained in 64 consecutive survivors of SCD due to ventricular fibrillation or tachycardia, who were treated with TH. Follow-up was 31.5 +/- 3.3 months in 41 ICD recipients and 36.3 +/- 3.9 months in 23 patients who did not receive an ICD due to the presence of a reversible cause of cardiac arrest, an acute myocardial infarction in 87%. Results: Combined incidence of ventricular arrhythmia, ICD therapy, or death in patients who underwent ICD placement (21.9%) were similar to overall mortality in the patients who did not receive an ICD (21.7%, p = 0.752). ICD placement was associated with a significant mortality benefit;95.1% survival in ICD recipients vs. 78.3% in the no-ICD group (p = 0.038). Electrocardiographic findings of ST segment elevation on admission were associated with increased event rate in ICD recipients (p = 0.039) and increased mortality in SCD patients who did not receive an ICD (p Conclusions: SCD survivors treated with TH are at increased risk for recurrent arrhythmic events and derive significant mortality benefit from ICD implantation. Increased mortality in revascularized SCD patients with acute coronary syndrome, thought to have a reversible cause of cardiac arrest, calls for prospective trials investigating utility of ICD in this vulnerable patient population.

Sudden Cardiac Death in Dakar: Epidemiological and Anatomo-Pathological Characteristics

Sudden cardiac death (SCD) generally refers to sudden cardiovascular death of a person with or without pre-existing heart disease. This is a retrospective study conducted at the Department of Anatomy and Pathological Cytology at Aristide Le Dantec Hospital in Senegal. This study covers a period of 7 years from January 1st, 2000 to December 31st, 2006. During this 7-year period we collected 235 cases of sudden cardiovascular death out of a total of 3717 forensic autopsies, representing a frequency of 6.32%. Sudden cardiovascular deaths accounted for 75.3% of all 312 sudden deaths. 96.1% were black compared to 3.9% Caucasians. The average age of the patients was 46.86 years with extremes ranging from 17 to 86 years. The most affected age group was between 50 - 59 years old, representing 23.4% of the cases. The sex ratio was 4.3 in favour of men. Men aged 50 - 59 were the most affected, while women were more affected in the 20 - 29 age group. Cardiomyopathies constituted 54.9% with 90% of dilated cardiomyopathies of which 75% were male and 10% of hypertrophic cardiomyopathies more frequent also in men. Valvulopathies came in 3rd position with 3.4% of the cases and in 75% of the cases they were poly-valvulopathies. Atherosclerosis was incriminated in 2.5% of the cases and aortic localization was the most represented. Aortic dissection was implicated in 6 cases out of 235 or 2.5%. It was isolated in 4 cases (without other cardiac conditions), and in the other 2 cases it was accompanied by other cardiac lesions including hypertrophy, pericarditis and endocarditis. The other causes found were interauricular communication (n = 1) and pericarditis (n = 2). Sudden cardiovascular death is a major global public health problem. The lack of epidemiological data on sudden death in Africa motivated our work, which led us to note that 75.3% of all sudden deaths in adults were of cardiovascular origin.