Helical CT versus intermittent CT fluoroscopic guidance for musculoskeletal needle biopsies: impact on radiation exposure, procedure time, diagnostic yield, and adverse events.

OBJECTIVE: Image-guided percutaneous needle biopsies are essential in the workup of musculoskeletal (MSK) lesions. While helical CT (HCT) is well established, intermittent CT fluoroscopy (iCTF) is an increasingly used alternative. The purpose of this study is to establish whether differences in subject radiation exposure, procedure time, yield, or adverse events exist between HCT and iCTF guidance. MATERIALS AND METHODS: This retrospective cohort study included consecutive MSK needle biopsies performed on a single-CT scanner over a 12-month period at a tertiary academic center. Subject demographics, radiation dose, and outcomes were abstracted from the medical record. Comparisons between the two cohorts were performed using Student's t-test for continuous data and using Fisher's exact test for categorical data and a two-tailed p value less than 0.05 was considered significant. RESULTS: Two hundred sixteen adults (115 (53.2%) females) with a mean age of 58.8 ± 18.4 years, underwent 216 biopsies (109 (50.5%) HCT guided, 107 (49.5%) iCTF guided) between June 2017 and June 2018. Dose-length product (DLP) and volume CT dose index (CTDIvol) were significantly higher for the HCT cohort (HCT 698.9 ± 400.8 mGycm vs iCTF 312.8 ± 170.8 mGycm; p < 0.005 and HCT 19.1 mGy ± 8.8 vs iCTF 6.9 mGy ± 1.5, p < 0.001). No significant difference in diagnostic yield, procedure time, or adverse event rate was identified. CONCLUSION: For CT-guided MSK needle biopsies, iCTF decreases subject radiation dose compared to HCT without negatively affecting outcomes. iCTF should be strongly considered by radiologists performing MSK biopsies given the reduced patient radiation exposure.

CT-guided bone marrow aspirations and biopsies: retrospective study and comparison with blind procedures.

PURPOSE: To compare the pathology results of CT-guided and blind bone marrow aspirations and biopsies. METHODS: Ninety-eight consecutive CT-guided biopsies and 98 age- and gender-matched blind (non-CT-guided) posterior iliac crest bone marrow aspirations and biopsies performed in 2017 were reviewed for adequacy of core biopsies and aspirate smears. CT procedure images and CT abdomen/pelvis images were reviewed to evaluate anatomic features of the posterior ilium and soft tissues. Statistical analysis was performed using a T test, Fisher exact test, and Kruskal-Wallis test. RESULTS: There was no significant difference in the age and gender of the two groups (p > 0.05). However, the CT-guided group had a higher BMI (p = 0.0049) and posterior soft tissue thickness (p = 0.0016). More CT-guided biopsy samples (CT 93 (95%); blind 77 (79%); p = 0.0006) and aspirate smears (CT 90 (92%); blind 78 (80%); p = 0.042) were categorized as adequate. The CT-guided group had longer core lengths (CT 1.4 ± 0.6 (range 0.3-3.5) cm; blind 1.0 ± 0.60 (range 0-2.6) cm; p = 0.0001). Overall, 131/164 (80%) of the cases had at least one of the described features (slanted posterior ilium (angle > 30°), 30%; rounded posterior ilium, 20%; thick posterior ilium cortex, 13%; focal lesion in posterior ilium, 12%; prior procedure in posterior ilium, 5%; posterior soft tissue thickness > 3 cm, 40%). CONCLUSION: CT-guided bone marrow procedures were more likely to result in both adequate aspirate smears and biopsy samples and longer core lengths when compared with blind procedures.

Association of fine-particulate and acidic-gas air pollution with premenstrual syndrome risk.

OBJECTIVE: Air pollution had been reported to be associated with the reproductive health of women. However, the association of particulate matter (PM) and acid gases air pollution with premenstrual syndrome (PMS) warrants investigation. This study investigated the effects of air pollution on PMS risk. POPULATION: We combined data from the Taiwan Air Quality-Monitoring Database and the Longitudinal Health Insurance Database. In total, an observational cohort of 85 078 Taiwanese women not diagnosed as having PMS. METHODS: Air pollutant concentrations were grouped into four levels based on the concentration quartiles of several types of air pollutants. MAIN OUTCOME MEASURES: We then applied univariable and multivariable Cox proportional hazard regression models to assess PMS risk in association with each pollutant type. RESULTS: Women exposed to Q4-level SO2 exhibited a 7.77 times higher PMS risk compared with those to Q1-level SO2 (95% confidence interval [CI] = 6.22-9.71). Women exposed to Q4-level NOx exhibited a 2.86 times higher PMS risk compared with those exposed to Q1-level NOx (95% CI = 2.39-3.43). Women exposed to Q4-level NO exhibited a 3.17 times higher PMS risk compared with women exposed to Q1-level NO (95% CI = 2.68-3.75). Finally, women exposed to Q4-level PM with a ≤2.5-µm diameter (PM2.5) exhibited a 3.41 times higher PMS risk compared with those exposed to Q1-level PM2.5 (95% CI = 2.88-4.04). CONCLUSIONS: High incidences of PMS were noted in women who lived in areas with higher concentrations of SO2, NOx, NO, NO2 and PM2.5.

Ethnic disparities in progression to advanced liver disease and overall survival in patients with chronic hepatitis C: impact of a sustained virological response.

BACKGROUND: Chronic hepatitis C (CHC) can lead to cirrhosis and hepatocellular carcinoma (HCC). A sustained virological response (SVR) is associated with improved outcomes, however, its impact on different ethnic groups is unknown. AIM: To evaluate ethnic differences in the natural history of CHC and the impact of SVR. METHODS: We conducted a cohort study of 8039 consecutive adult CHC patients seen at two medical centres in California between January 1997 and June 2016. Individual chart review confirmed CHC diagnosis. RESULTS: Asian and Hispanic but not African American patients had significantly higher cirrhosis and HCC incidence than Caucasians. On multivariate analysis, Hispanic ethnicity was independently associated with increased cirrhosis (adjusted HR 1.37, CI, confidence interval 1.10-1.71, P=.006) and HCC risk (adjusted HR 1.47, CI 1.13-1.92, P=.004) compared to Caucasian. Asian ethnicity had a significant association with cirrhosis (adjusted HR 1.28, CI 1.02-1.61, P=.034) and HCC risk (adjusted HR 1.29, CI 0.94-1.77, P=.025). In patients who achieved SVR, Hispanic ethnicity was no longer independently associated with cirrhosis (adjusted HR 1.76, CI 0.66-4.71, P=.26) or HCC (adjusted HR 1.05, CI 0.27-4.08, P=.94); nor was Asian ethnicity (adjusted HR 0.62, CI 0.21-1.82, P=.38 for cirrhosis; 2.01, CI 0.63-6.36, P=.24 for HCC). Similar findings were observed with overall survival among the ethnicities by SVR status. CONCLUSION: Hispanic and Asian ethnicity was independently associated with increased cirrhosis and HCC risk. Achieving an SVR eliminates the ethnic disparity in liver disease progression and overall survival between Hispanic and Asian vs Caucasian CHC patients.

Expression of CALR mutants causes mpl-dependent thrombocytosis in zebrafish.

CALR mutations are identified in about 30% of JAK2/MPL-unmutated myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET) and primary myelofibrosis. Although the molecular pathogenesis of CALR mutations leading to MPNs has been studied using in vitro cell lines models, how mutant CALR may affect developmental hematopoiesis remains unknown. Here we took advantage of the zebrafish model to examine the effects of mutant CALR on early hematopoiesis and model human CALR-mutated MPNs. We identified three zebrafish genes orthologous to human CALR, referred to as calr, calr3a and calr3b. The expression of CALR-del52 and CALR-ins5 mutants caused an increase in the hematopoietic stem/progenitor cells followed by thrombocytosis without affecting normal angiogenesis. The expression of CALR mutants also perturbed early developmental hematopoiesis in zebrafish. Importantly, morpholino knockdown of mpl but not epor or csf3r could significantly attenuate the effects of mutant CALR. Furthermore, the expression of mutant CALR caused jak-stat signaling activation in zebrafish that could be blocked by JAK inhibitors (ruxolitinib and fedratinib). These findings showed that mutant CALR activates jak-stat signaling through an mpl-dependent mechanism to mediate pathogenic thrombopoiesis in zebrafish, and illustrated that the signaling machinery related to mutant CALR tumorigenesis are conserved between human and zebrafish.

The mortality and direct medical costs of osteoporotic fractures among postmenopausal women in Taiwan.

UNLABELLED: This study estimated the fracture-related mortality and direct medical costs among postmenopausal women in Taiwan by fracture types and age groups by utilizing a nationwide population-based database. Results demonstrated that hip fractures constituted the most severe and expensive complication of osteoporosis across fracture sites. INTRODUCTION: The aims of the study were to evaluate the risk of death and direct medical costs associated with osteoporotic fractures by fracture types and age groups among postmenopausal women in Taiwan. METHODS: This nationwide, population-based study was based on data from the National Health Insurance Research Database in Taiwan. Female patients aged 50 years and older in the fracture case cohort were matched in 1:1 ratio with randomly selected subjects in the reference control cohort by age, income-related insurance amount, urbanization level, and the Charlson comorbidity index. There were two main outcome measures of the study: age-differentiated mortality and direct medical costs in the first and subsequent years after osteoporotic fracture events among postmenopausal women. The bootstrap method by resampling with replacement was conducted to generate descriptive statistics of mortality and direct medical costs of the case and control cohorts. Student's t tests were then performed to compare mortality and costs between the two cohorts. RESULTS: A total of 155,466 postmenopausal women in the database met the inclusion criteria for the fracture case cohort, including 22,791 hip fractures, 72,292 vertebral fractures, 15,621 upper end humerus (closed) fractures, 36,774 wrist fractures, and 7,988 multiple fractures. Analytical results demonstrated that patients experiencing osteoporotic fractures were at considerable excess risk of death and incurred substantially higher treatment costs, notably for hip fractures. Furthermore, results also revealed that the risk of mortality increased with advancing age across the spectrum of fracture sites. CONCLUSIONS: The present study confirmed an excess mortality and higher direct medical costs associated with osteoporotic fractures. Moreover, hip fractures constituted the most severe and expensive complication of osteoporosis among fracture types.

Stapedectomy Effects on Tinnitus: Relationship of Change in Loudness to Change in Severity.

OBJECTIVE: To relate poststapedectomy change in tinnitus loudness to change in tinnitus severity. STUDY DESIGN: Prospective, within-subjects. SETTING: A single otology and neurotology subspecialty referral practice. SUBJECTS AND METHODS: Forty-nine subjects undergoing stapedectomy completed the study between January 2012 and October 2013. Tinnitus instruments, audiometric data, and demographic information were collected prior to and 1 and 6 months after surgery. Tinnitus loudness was assessed using an 11-point (0 = none; 5 = conversation level; 10 = jet engine) visual analog scale, and severity was measured using the validated Tinnitus Functional Index. The relationship between change in tinnitus loudness and change in tinnitus severity was evaluated using linear regression and receiver operating characteristic (ROC) analyses. RESULTS: A linear regression model of change in tinnitus loudness averaged for both ears on a visual analog scale (ΔVASavg) versus change in Tinnitus Functional Index score (ΔTFI) showed a strong correlation (ΔTFI = 9.35 ×ΔVASavg; R = 0.64; P < .001). An ROC analysis identified ΔVASavg between 1.5 and 2.0 as the optimal threshold for predicting a clinically significant change in tinnitus severity (ΔTFI ≥ 13), with sensitivity and specificity of approximately 0.62 and a positive predictive value (PPV) of 0.64. CONCLUSION: For poststapedectomy patients, a VAS loudness change by 1.5 to 2.0 points averaged for both ears in bilateral tinnitus or ~3 points in unilateral tinnitus has a PPV ~0.64 for a clinically significant change in tinnitus severity.

Human herpes virus reactivations and dynamic cytokine profiles in patients with cutaneous adverse drug reactions --a prospective comparative study.

BACKGROUND: Sequential human herpes virus (HHV) reactivation is well known in drug reaction with eosinophilia and systemic symptom (DRESS), but such a phenomenon has seldom studied in other types of cutaneous adverse drug reactions (cADRs). Moreover, the association between viral reactivations and cytokine or chemokine changes is largely unknown. We aimed to evaluate the viral reactivation rates of HHV-6, HHV-7, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in different cADRs and their impacts on clinical prognosis. Cytokine and chemokine changes with viral reactivations were also examined. METHODS: A prospective study was conducted to monitor the viral statuses of patients with different cADRs by polymerase chain reaction and serum-specific antibody titers. Changes in plasma cytokine and chemokine levels were also evaluated by sequential blood samples. RESULTS: Among the various cADRs, HHV-6 reactivation was only observed in DRESS, but EBV and CMV could be detected in other cADRs. Many proinflammatory cytokines and chemokines, including interleukin (IL)-1ß, IL-2, IL-6, interferon-γ, tumor necrosis factor-α, were significantly lower in DRESS patients with HHV-6 reactivation when compared to those without HHV-6 reactivation. In addition, these mediators were significantly lower before and during HHV-6 reactivation, compared to cytokine levels after HHV-6 reactivation in the same patient. CONCLUSION: HHV-6 reactivation was only observed in DRESS patients, not in any other cADR. In DRESS patients, some proinflammatory cytokines were significantly lower before or during HHV-6 reactivation.

The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer.

Despite increased survivorship among patients, breast cancer remains the most common cancer among women and is the second leading cause of cancer death in women. The magnitude of this problem provides a strong impetus for new chemopreventative strategies and/or lifestyle changes that reduce cancer incidence. It is of significance, therefore, that several studies positively correlate obesity to the development of breast cancer. Importantly, obesity is also highly associated with elevated cholesterol, and cholesterol itself is a risk factor for breast cancer. Furthermore, patients taking statins demonstrate a lower breast cancer incidence and decreased recurrence. The recent observation that 27-hydroxycholesterol (27HC) is produced in a stoichiometric manner from cholesterol, together with our recent demonstration that it exerts partial agonist activity on both the estrogen and liver X receptors, suggested a potential mechanistic link between hyper-cholesterolemia and breast cancer incidence. Using genetic and pharmacological approaches, we have recently shown that elevation of circulating 27HC significantly increases tumor growth and metastasis in murine models of breast cancer. Further, we have demonstrated in appropriate animal models that the impact of high-fat diet on tumor pathogenesis can be mitigated by statins or by small molecule inhibitors of CYP27A1. These findings suggest that pharmacological or dietary modifications that lower total cholesterol, and by inference 27HC, are likely to reduce the impact of obesity/metabolic syndrome on breast cancer incidence.

Tinnitus modulation by stapedectomy.

OBJECTIVE: To assess change in tinnitus severity after stapedectomy using the validated Tinnitus Functional Index (TFI) at 1 and 6 months in 2 cohorts of subjects with otosclerosis with different preoperative (TFIpre) distress levels. STUDY DESIGN: Prospective within-subjects repeated measures. MATERIALS AND METHODS: Twenty-six subjects completed the study between January 2012 and April 2013. Demographic information, preoperative and postoperative audiometric data at 1 month, and TFI scores measured preoperatively within 1 month of stapedectomy and postoperatively at 1 and 6 months were captured and analyzed. RESULTS: Stapedectomy has its largest effect on tinnitus severity reduction within the first month of surgery. Cohort A (TFIpre > 15, n = 16) ΔTFI mean and median values were ∼20 for the intervals preoperatively to 1 month and preoperatively to 6 months (p values < 0.01) and dropped to ∼0 for the interval between 1 and 6 months postoperatively. Cohort B (TFIpre < 15, n = 10) ΔTFI mean and median values were ∼0 for all time intervals (all pairwise comparison p values > 0.05). CONCLUSION: Stapedectomy in patients with otosclerosis with more than a small problem with tinnitus (TFIpre > 15) will reduce severity by at least 1 clinical category in ∼85% of cases within 6 months of surgery. The majority of patients will experience stable tinnitus suppression within the first postoperative month. In patients with no tinnitus or less than a small problem with tinnitus (TFIpre < 15), stapedectomy carries a 10% risk of transient worsening of tinnitus at 1 month, which resolves by the sixth postoperative month.

Cardiac transplantation and concomitant coronary artery bypass grafting: our experiences in 11 cases.

INTRODUCTION: The shortage of donor hearts for transplantation could be alleviated by including the hearts of older donors. Previous literature revealed similar early and medium-term survival outcomes compared with those of younger donors. This study presents our experience with patients who underwent orthotopic heart transplantation and concomitant coronary artery bypass grafting at our institution. METHODS: We present our experience with 11 patients with end-stage cardiomyopathy (8 men and 3 women) undergoing orthotopic heart transplantation and concomitant coronary artery bypass grafting from September 2002 to November 2011 at our institute. RESULTS: All 11 donor organs would otherwise have been rejected, depriving potential recipients of organ transplantation. Two patients received concurrent 2-coronary-artery bypass, and the other 9 patients received concurrent single-coronary-artery bypass during orthotopic heart transplantation. All patients had an uneventful postoperative course, with follow-up completed 3 to 128 months after cardiac transplantation and concomitant coronary artery bypass grafting surgery. CONCLUSIONS: Our experiences suggest that donor hearts requiring coronary artery bypass grafting, which form a small but significant donor subgroup, can be used effectively and safely when matched to the recipients' age and medical condition.

Evaluation of the outcomes of endovascular management for patients with head and neck cancers and associated carotid blowout syndrome of the external carotid artery.

AIM: To evaluate factors related to the technical and haemostatic outcomes of endovascular management in patients with head and neck cancers (HNC) associated with carotid blowout syndrome (CBS) of the external carotid artery (ECA). MATERIALS AND METHODS: Between 2002 and 2011, 34 patients with HNC with CBS involving branches of the ECA underwent endovascular therapy. Treatment included embolization with microparticles, microcoils, or acrylic adhesives. Fisher's exact test was used to examine demographic features, clinical and angiographic severities, and clinical and imaging findings as predictors of endovascular management outcomes. RESULTS: Technical success and immediate haemostasis were achieved in all patients. Technical complications were encountered in one patient (2.9%). Rebleeding occurred in nine patients (26.5%). Angiographic vascular disruption grading from slight (1) to severe (4) revealed that the 18 patients with acute CBS had scores of 2 (2/18, 11.1%), 3 (3/18, 16.7%), and 4 (13/18, 72.2%). The 16 patients with impending and threatened CBS had scores of 1 (1/16, 6.25%), 2 (5/16, 31.25%), and 3 (10/16, 62.5%; p = 0.0003). For the 25 patients who underwent preprocedural computed tomography (CT)/magnetic resonance imaging (MRI) examinations within 3 months of treatment, the agreement between clinical and imaging findings reached the sensitivity, specificity, and kappa values for recurrent tumours (1, 0.7143, 0.7826), soft-tissue defect (0.9091, 0.3333, 0.2424), and sinus tract/fistula (0.4737, 0, 0.4286). CONCLUSION: Endovascular management for patients with CBS of the ECA had high technical success and safety but was associated with high rebleeding rates. We suggest applying aggressive post-procedural follow-up and using preprocedural CT/MRI to enhance the periprocedural diagnosis.

Can iterative reconstruction improve imaging quality for lower radiation CT perfusion? Initial experience.

BACKGROUND AND PURPOSE: Initial results using IR for CT of the head showed satisfactory subjective and objective imaging quality with a 20-40% radiation dose reduction. The aim of our study was to compare the influence of IR and FBP algorithms on perfusion parameters at standard and lowered doses of CTP. MATERIALS AND METHODS: Forty patients with unilateral carotid stenosis post-carotid stent placement referred for follow-up CTP were divided into 2 groups (tube currents were 100 mAs in group A and 80 mAs in group B). Datasets were reconstructed with IR and FBP algorithms; and SNRs of gray matter, white matter, and arterial and venous ROIs were compared. CBF, CBV, and MTT means and SNRs were evaluated by using linear regression, and qualitative imaging scores were compared across the 2 algorithms. RESULTS: The mean effective radiation dose of group B (2.06 mSv) was approximately 20% lower than that of group A (2.56 mSv). SNRs for ROIs in the dynamic contrast-enhanced images were significantly higher than those for the FBP images. Correlations of the SNRs for CBF, CBV, and MTT across the 2 algorithms were moderate (R² = 0.46, 0.23, and 0.44, respectively). ROIs in gray matter rather than the IR algorithm predicted increasing SNRs in all CBF, CBV, and MTT maps. Two cases of significant restenosis were confirmed in both algorithms. CBV, CBF, and MTT imaging scores did not differ significantly across algorithms or groups. CONCLUSIONS: Lower dose CTP (20% below normal dose) without IR can effectively identify oligemic tissue in poststenting follow-up. IR does not alter the absolute values or increase the SNRs of perfusion parameters. Other methods should be attempted to improve SNRs in settings with low tube currents.

Long-term follow-up of arrhythmia characteristics and clinical outcomes in heart transplant patients.

INTRODUCTION: Arrhythmias occur frequently after heart transplantation (HT), but knowledge of their impact on long-term outcomes is limited. This study sought to investigate the characteristics of the arrhythmias among biatrial orthotopic HT patients during long-term follow-up. METHODS: This study included 217 patients who received biatrial orthotopic HT. Patients were classified into 5 groups according to the arrhythmia episodes that occurred >1 month after HT: no arrhythmias (group 1; n = 149); atrial tachyarrhythmias only (group 2; n = 34); ventricular tachyarrhythmias only (group 3; n = 9); bradyarrhythmias only (group 4; n = 7); or double/triple arrhythmias (group 5; n = 18). We analyzed their long-term outcomes respectively. RESULTS: During 83 ± 51 months of follow-up, all-cause mortality rates were higher in groups 3 (88.9%) and 5 (72.2%) compared with the other groups (groups 1, 2, and 4: 21.5%, 41.2%, and 57.1%, respectively; P < .001). Cardiovascular mortality rates were higher in groups 4 (42.9%) and 5 (61.1%) compared with the other groups (groups 1, 2, and 3: 8.1%, 20.6%, and 0% respectively; P < .001). Noncardiovascular mortality rate was greater in group 3 (88.9%) compared with the other groups (groups 1, 2, 4, and 5: 13.4%, 20.6%, 14.3%, and 11.1%, respectively; P < .001). Sudden death rates were higher in groups 4 (42.9%) and 5 (44.4%) compared with the other groups (groups 1, 2, and 3: 7.4%, 8.8%, and 0%, respectively; P < .001). CONCLUSION: Patients with posttransplantation arrhythmias experienced significantly worse clinical outcomes.

Adverse postoperative outcomes in surgical patients with immune thrombocytopenia.

BACKGROUND: Patients with immune thrombocytopenia (ITP) are likely to have various medical co-morbidities, yet their global features regarding adverse postoperative outcomes and use of medical resources when undergoing major surgery are unknown. The objective of this study was to validate whether ITP is an independent risk factor for adverse postoperative outcomes, and to explore the potential clinical predictors of outcomes after major surgery among patients with ITP. METHODS: A retrospective population-based cohort study was conducted using Taiwan's National Health Insurance Research Database, controlling for preoperative co-morbidities by means of multiple logistic regression. Major postoperative complication and mortality rates, and in-hospital medical costs were analysed. RESULTS: The study included 11,085 surgical patients with ITP and 44,340 controls without ITP matched for sex, age, and type of surgery and anaesthesia. Surgical patients with ITP had a higher risk of postoperative death (odds ratio (OR) 1.89, 95 per cent confidence interval 1.57 to 2.27), and overall postoperative complications (OR 1.47, 1.39 to 1.56), and increased hospital stay (OR 1.90, 1.80 to 2.01), admission to the intensive care unit (OR 1.73, 1.63 to 1.83) and medical costs (OR 1.89, 1.79 to 1.99). Amount of preoperative platelet and/or red blood cell transfusion, emergency visits and admission to hospital for ITP care were identified as risk factors for adverse postoperative outcomes. CONCLUSION: Patients with ITP undergoing surgery are at increased risk of adverse perioperative events, particularly if blood or blood product transfusion are required preoperatively, or the procedure is done as an emergency.

Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma.

BACKGROUND: Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma (HCC). The bioenergetic propensity of cancer cells has been correlated to anticancer drug resistance, but such correlation is unclear in sorafenib resistance of HCC. METHODS: Six sorafenib-naive HCC cell lines and one sorafenib-resistant HCC cell line (Huh-7R; derived from sorafenib-sensitive Huh-7) were used. The bioenergetic propensity was calculated by measurement of lactate in the presence or absence of oligomycin. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, and siRNA of hexokinase 2 (HK2) were used to target relevant pathways of cancer metabolism. Cell viability, mitochondrial membrane potential, and sub-G1 fraction were measured for in vitro efficacy. Reactive oxygen species (ROS), adenosine triphosphate (ATP) and glucose uptake were also measured. A subcutaneous xenograft mouse model was used for in vivo efficacy. RESULTS: The bioenergetic propensity for using glycolysis correlated with decreased sorafenib sensitivity (R(2)=0.9067, among sorafenib-naive cell lines; P=0.003, compared between Huh-7 and Huh-7 R). DCA reduced lactate production and increased ROS and ATP, indicating activation of oxidative phosphorylation (OXPHOS). DCA markedly sensitised sorafenib-resistant HCC cells to sorafenib-induced apoptosis (sub-G1 (combination vs sorafenib): Hep3B, 65.4±8.4% vs 13±2.9%; Huh-7 R, 25.3± 5.7% vs 4.3±1.5%; each P<0.0001), whereas siRNA of HK2 did not. Sorafenib (10 mg kg(-1) per day) plus DCA (100 mg kg(-1) per day) also resulted in superior tumour regression than sorafenib alone in mice (tumour size: -87% vs -36%, P<0.001). CONCLUSION: The bioenergetic propensity is a potentially useful predictive biomarker of sorafenib sensitivity, and activation of OXPHOS by PDK inhibitors may overcome sorafenib resistance of HCC.

Combined St. Thomas and histidine-tryptophan-ketoglutarat solutions for myocardial preservation in heart transplantation patients.

BACKGROUND: To establish quicker cardiac arrest and less myocardial distension injury during heart procurement, we combined St. Thomas and histidine-tryptophan-ketoglutarate (HTK) solutions for donor heart preservation since June 2008. METHODS: From June 2008 to March 2010, we enrolled 31 heart transplantation (HT) patients in this study. During heart procurement we initially infused 1,000 mL cold St Thomas cardioplegic solution to achieve cardiac arrest. After procurement, a further 2,000 mL of cold HTK solution was infused at low perfusion pressure. Another 1,000 mL cold HTK solution was perfused before donor heart implantation. We examined donor age, recipient preoperative characteristics, ischemia time, hospital stay, postoperative graft function, major cardiac events, and transplant vasculopathy (TCAD). RESULTS: Twenty-two patients (71.0%) presented with dilated cardiomyopathy and 7 (23.3%) with ischemia cardiomyopathy. There were 23 (76.7%) male donors, and the mean donor age was 38.4 ± 13.8 years. Six patients underwent a redo sternotomy, 1 patient needed a third-do sternotomy, and 1 a seventh sternotomy (third HT) for repeated endocarditis and graft failure. The average ischemia time was 224.9 ± 71.0 minutes and the postoperative hospital stay was 57.7 ± 47.7 days. The surgical mortality (3.2%) was not accompanied by hospital or follow-up mortality. Patient left ventricular ejection fraction postoperative was 59.6 ± 2.3% with good functional status. Major cardiac events occurred in 8 patients (26.7%) without major complications. There were two subjects with TCAD but normal graft function. The correlation between ischemia time and hospital stay was insignificant (r = 0.21; P = .26). CONCLUSIONS: Donor heart preservation combining St Thomas cardioplegic arest and low-pressure perfusion with HTK solution seemed to be safe with. short-term survival similar to other approaches.

Prosthetic endocarditis treated by repeated heart transplantation: report of a successful case.

The treatment of recurrent prosthetic valve endocarditis is extremely difficult. Heart transplantation (HT) may save the patient's life. Recurrent endocarditis, however, can occur after HT. This report described a patient who had under gone four conventional valve surgeries and three HTs successfully. In May 2000, a 14-year-old boy suffered from endocarditis with severe aortic valve regurgitation. He underwent aortic valve replacement (AVR) at another hospital. Due to prosthetic valve endocarditis, he displayed a severe paravalvular leakage and was transferred to our hospital where he underwent Bentall's operation in October 2000. Despite a full antibiotic course, he experienced a relapse of the prosthetic endocarditis with significant deterioration of the heart function and a progressively more severe paravalvular leak. Considering the difficulties of repair and the poor heart function, he underwent an HT in June 2003 and recovered well. Unfortunately, endocarditis with aortic valve regurgitation attacked him again after 3 years. Remarkably, all blood cultures were negative. A second AVR was performed in October 2006 with a Second Bentall's procedure 1 year later in 2007. In November 2009, the patient suddenly displayed cardiogenic shock with collapse. He was transferred to our hospital and needed extracorporcal membrane oxygenation (ECMO) support. Two days later, he underwent a second HT. However, the donor heart was nonfunctional due to the prolonged ischemia time. ECMO support was continuously needed after the HT. A third HT was performed successfully 10 days later. Due to previous reported experiences of culture-negative endocarditis, minocycline was prescribed twice daily continuously after the third HT/seventh cardiac surgery. The patient was discharged 2 months later. To date he takes minocycline every day and lives a healthy life.

Combined heart transplantation and total replacement of thoracic aorta in Marfan's syndrome with recurrent aortic dissection: a case report.

It is extremely rare for a patient to need simultaneous heart transplantation (HTx) and replacement of the thoracic aorta. A 23-year-old woman with Marfan's syndrome underwent Bentall's operation and replacement of the ascending aorta (AsA) due to a type A aortic dissection (AD) in August 2001. In March 2005, she began to experience dyspnea on exertion and was found to have a huge pseudoaneurysm at the aortic root, which had caused dehiscence of the aortic conduit. In July 2009, she suffered acute chest pain followed by hypotension and cold sweating. The computed tomography (CT) scan showed a recurrent dissection with a long intimal tear extending from the arch to the mid-portion of the descending thoracic aorta (DTA). Due to technical difficulties in the repair of the aortic root, she was placed on the HTx waiting list. The next day, she received a donor heart and underwent combined HTx and total replacement of the thoracic aorta. Explantation of the heart improved the exposure of the DTA. With the use of a vascular ring connector (Vasoring), the operation was successfully performed without need for a blood transfusion. The patient was still well at 2 years after the operation. Simultaneous replacement of the heart and the whole segment of the thoracic aorta is technically possible in Marfan patients who are complicated with aortic dissection.