Iodized oil enhances the thermal effect of high-intensity focused ultrasound on ablating experimental liver cancer

The influence of the biological medium on high-intensity focused ultrasound (HIFU) therapy for ablating experimental liver cancer was studied. In study 1, the temperature rise in the focal zone in the presence of iodized oil or castor oil was observed in vitro. The results showed that HIFU with iodized oil produced a higher and faster temperature rise than did HIFU with castor oil, whether high-power (500 W/cm²) or relatively low-power (136 W/cm²) conditions were used (P=0.0008 and P=0.0004 respectively). With the excised liver samples, the temperature also rose higher and more rapidly after injection of iodized oil into the liver than when castor oil was injected (P=0.0239), and the target liver tissue revealed more radically and extensive destruction with iodized oil than with castor oil. In study 2, 48 nude mice, bearing primary liver cancer LTNM₄ implanted subcutaneously, were randomly divided into four groups. Group I (n=12) were the controls, group II (n=12) were injected with iodized oil alone, group III (n=12) received HIFU treatement, and group IV (n=12) were exposed to HIFU after iodized oil injection. Significant inhibition of tumor growth was seen in groups III and IV as compared with group I or group II (P<0.05), the tumor growth inhibition rate on the 28th day after treatment being 87% and 93% respectively. Significantly improved survival was noted in groups III and IV compared with groups I and II (P<0.05). Histologically, group IV showed more complete tumor necrosis than did group III. These data suggest that HIFU combined with iodized oil might have achieve of synergism, location and targeting in the treatment of liver cancer.     

Conditional knockout of heparin‐binding epidermal growth factor‐like growth factor in the liver accelerates carbon tetrachloride‐induced liver injury in mice

Aim: We previously demonstrated that heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) is induced in response to several liver injuries. Because the HB‐EGF knockout (KO) mice die in utero or immediately after birth due to cardiac defects, the loss of function study in vivo is limited. Here, we generated liver‐specific HB‐EGF conditional knockout mice using the interferon‐inducible Mx‐1 promoter driven cre recombinase transgene and investigated its role during acute liver injury. Methods: We induced acute liver injury by a single i.p. injection of carbon tetrachloride (CCl₄) in HB‐EGF KO mice and wild‐type mice and liver damage was assessed by biochemical and immunohistochemical analysis. We also used AML12 mouse hepatocyte cell lines to examine the molecular mechanism of HB‐EGF‐dependent anti‐apoptosis and wound‐healing process of the liver in vitro. Results: HB‐EGF KO mice exhibited a significant increase of alanine aminotransferase level and also showed a significant increase in the number of apoptotic hepatocytes assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining at 24 h after CCl₄ injection. We also demonstrated that HB‐EGF treatment inhibited tumor necrosis factor‐α‐induced apoptosis of AML12 mouse hepatocytes and promoted the wound‐healing response of these cells. Conclusion: This study showed that HB‐EGF plays a protective role during acute liver injury.     

Growth inhibition of liver metastases by the anti‐angiogenic drug TNP‐470

Abstract: Objective: This study was undertaken in order to assess the efficacy of a potent angiogenesis inhibitor, TNP‐470, on tumor growth in a syngeneic rodent model of liver metastases from colorectal cancer. Background: New blood vessel formation is a prerequisite for primary and metastatic tumor growth. TNP‐470, a synthetic derivative of fumagillin when subcutaneously transplanted into nude mice, inhibits endothelial cell proliferation and migration, as well as the growth of various human cancers. However, the antitumor effect of this drug has not been studied in models reproducing a natural metastatic environment. Since the liver provides an extensive vascular bed for secondary tumor growth, an anti‐angiogenic strategy may therefore be less efficient for treating hepatic metastases than primary tumors. Methods: 10⁷ DHD K12 colon carcinoma cells were injected intrasplenically into syngeneic BD IX rats to produce diffuse liver metastases. TNP‐470 (30 mg/kg/day) was administered on alternate days starting 4 days after tumor implantation. The animals were sacrificed after 4 weeks and their livers were processed for histologic examination. In both the treatment and control groups (n=7), tumor volume was determined using a computerized analytical system, and tumor microvessel density was measured by immunostaining with anti‐von Willebrand Factor monoclonal antibody. Results:In vitro, TNP‐470 demonstrated a direct toxicity towards the DHD K12 cell line with an IC₅₀ of 0.1 μg/ml. Metastases were present in all animals from both groups. Liver weight (15.2 g vs 11.7 g, p=0.01), and tumor volume (1218 mm³ vs 406 mm³, p=0.03) were significantly reduced in the TNP‐470 group compared to the control group. Tumor microvessel density was not statistically different between the two groups (67 vs 63 microvessels/×200 field, p=0.41). Conclusion: TNP‐470 inhibits the growth of liver metastases in a syngeneic rat model of colorectal cancer. The mechanism responsible for this effect remains unclear, but may involve a combination of anti‐angiogenic and direct cytotoxic effects.     

Therapeutic vaccination (p24‐VLP) of patients with advanced HIV‐1 infection in the pre‐HAART era does not alter CD4 cell decline

Summary In a randomized placebo controlled trial 304 HIV infected patients with CD4 cell counts below 350 cells/µL received therapeutic vaccination with: alum placebo (Group I, n = 102), p24‐VLP 500 µg (Group II, n = 101) or p24‐VLP 1000 µg (Group III, n = 101) p24‐VLP monthly for six months. Over one year the average change in CD4 cell count did not differ significantly between groups (–32, –40 and –52 cells per μL respectively). There was also no difference between groups in progression to CDC catagory B or C events, or in adverse events. Therapeutic vaccination with p24‐VLP does not affect CD4 cell decline in patients with advanced HIV infection.     

Comparative serum proteomic analysis of patients with acute‐on‐chronic liver failure: alpha‐1‐acid glycoprotein maybe a candidate marker for prognosis of hepatitis B virus infection

Summary. The acute‐on‐chronic liver failure (AoCLF) caused by hepatitis B virus (HBV) infection remains to be a challenge in clinics with a high mortality rate in China, and it is important to identify biomarkers to foresee the prognosis of patients with HBV. The current study analysed serum proteome changes of acute‐on‐chronic liver failure as a result of acute exacerbation of chronic hepatitis B infection. Serum samples were collected from normal subjects (NS, n = 8), patients with chronic hepatitis B (CHB, n = 12) and patients with AoCLF (n = 12). After removal of albumin/IgG and ultramembrane centrifugation, serum proteins were separated by two‐dimensional gel electrophoresis. Differentially expressed spots were identified by matrix‐associated laser desorption ionization time‐of‐flight tandem mass spectrometry. Through the removal of albumin/IgG and ultramembrane centrifugation, the well‐resolved and reproducible two‐dimensional gel electrophoresis (2‐DE) profiles were obtained. A total of 23 proteins were identified on 2‐DE profiles by their differential expression between the three cohorts. Mass spectrometry analysis resulted in the identification of 12 proteins unambiguously. Western blot analysis confirmed the proteomics results that the α1‐acid glycoprotein (α1‐AGP) levels decrease significantly in plasma of patients with AoCLF, but somewhat decreased in patients with chronic HBV. Further α1‐AGP levels in bulk serum samples were measured by immune turbidimetry including normal subjects group (n = 25), acute hepatitis group (n = 36), chronic hepatitis group (n = 52) and AoCLF group (n = 48), the level of α1‐AGP in AoCLF groups sharply decrease than other groups. Our study shows that α1‐AGP may be a potential plasma biomarker for AoCLF diagnosis because of acute exacerbation of chronic hepatitis B infection.     

Detection of D‐3‐phosphoglycerate dehydrogenase autoantibodies in patients with autoimmune hepatitis: Clinical significance evaluation

Aim: D‐3‐phosphoglycerate dehydrogenase (3‐PHGDH) was identified as a putative target of autoantibodies in autoimmune hepatitis (AIH). The aims of the present study were to detect anti‐3‐PHGDH in patients with AIH and other chronic liver diseases and to analyze their clinical relevance. Methods: Human 3‐PHGDH gene was cloned and expressed in Escherichia coli and used in enzyme‐linked immunosorbent assays and Western blots. Serum from patients with AIH (n = 101), primary biliary cirrhosis (PBC, n = 122), chronic hepatitis C (CHC, n = 117), chronic hepatitis B (CHB, n = 112), and from patients with other autoimmune disease (n = 125) were investigated. Results: The highest incidence and activity of anti‐PHGDH was observed in AIH patients. Thirty‐two of 40 untreated (80%) and 37 of 61 AIH patients treated with corticosteroid (60.7%) were positive. Antibody titers decreased significantly during corticosteroid treatment. 15.8% of PBC patients, 9.8% of CHB and 12.8% of CHC patients, were anti‐PHGDH‐positive, with less than 12% of patients positive with other autoimmune diseases via reactions with recombinant 3‐PHGDH protein. Conclusion: Anti‐PHGDH were detected in chronic liver diseases. They occur predominantly in AIH, and corticosteroid treatment seems to decrease antibody titers. Whether the antibodies are primary or secondary phenomena and whether they are related to the etiology or pathogenesis, at least in a subgroup of patients with chronic liver diseases, has still to be evaluated.     

Liver analysis using gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid‐enhanced magnetic resonance imaging: Correlation with histological grading and quantitative liver evaluation prior to hepatectomy

Aim: To examine the effectiveness of gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI) in the assessment of parenchymal liver fibrosis and quantitative liver function prior to hepatectomy. Methods: Between July 2008 and September 2011, the data of 93 consecutive patients undergoing preoperative Gd‐EOB‐DTPA‐enhanced MRI were analyzed, including serum fibrosis marker levels (hyaluronic acid, type IV collagen), 15‐min retention rates of indocyanine green (ICG‐R15) in the ICG clearance test, and technetium‐99m galactosyl serum albumin scintigraphy results. Liver intensity values were obtained by calculating the differences between the intensity of the liver and that of other organs in the hepatobiliary phase. Degrees of liver fibrosis were quantitatively assessed (F0–4). MRI data were correlated with the prospectively acquired clinical data. Results: Varying degrees of liver fibrosis were detected in 31 of the 93 patients. The intensity ratio of the liver to spinal cord on MRI negatively correlated with hepatic fibrosis (R = ?0.479, P < 0.001) and ICG‐R15 (R = ?0.492, P < 0.001). When patients with F0–2 (normal/moderate) and F3–4 (severe) liver fibrosis were compared, the intensity ratio of the enhanced liver to spinal cord (IRLS) on MRI was significantly lower in the F3–4 group than in the F0–2 group. IRLS was correlated with liver fibrosis, and, when an IRLS criterion of less than 1.702 was used, severe liver fibrosis could be predicted with 68.8% sensitivity and 93.5% specificity. Conclusion: Preoperative Gd‐EOB‐DTPA‐enhanced MRI analysis can detect quantitative indicators of liver fibrosis and function, thus aiding the assessment of hepatic remnants prior to hepatectomy.     

Insulin‐like growth factor‐I restores the reduced somatostatinergic tone controlling growth hormone secretion in cirrhotic rats

Abstract: Background/Aims: An altered growth hormone/insulin‐like growth factor‐I (GH/IGF‐I) axis occurs in advanced liver cirrhosis, characterised by diminished serum levels of IGF‐I and increased concentrations of GH. Under normal conditions, GH release is mediated by somatostatin (SS) inhibition. However, the influence of SS on GH release in cirrhosis is not well known. IGF‐I supplementation has beneficial effects in experimental cirrhosis, and – under physiological conditions – IGF‐I increases SS, inhibiting GH. The aims of this work were to study SS tone in cirrhotic animals and to evaluate whether IGF‐I treatment influences SS tone, controlling GH secretion in cirrhosis. Methods: We studied the influence of SS on GH secretion by assessing GH response to pyridostigmine (PD) in cirrhotic rats treated and untreated with IGF‐I. Liver cirrhosis was induced with CCl₄‐inhalation for 11 weeks in male Wistar rats. The animals were randomly divided into two groups: CI+IGF (n=12), which received IGF‐I treatment for 12 days (2 μg/100 g body wt^?1×d^?1) and CI (n=12), which received saline. Healthy controls (CO, n=12) were studied at the same time. On day 13, animals from each group were subdivided into two groups (n=6) in order to explore the effect of a PD intrajugular bolus (10 μg×100 gbw^?1) on serum GH levels (at 0,10,20,30 and 60 min), which were assessed by RIA. Results: PD bolus did not exert any effect on GH serum levels in the CI group, suggesting a low SS tone in cirrhotic rats. However, PD induced an increase in GH levels into CO and CI+IGF groups. In conclusion, as occurs under normal conditions, the cholinergic system is a significant modulator of GH secretion in experimental liver cirrhosis. Conclusion: Cirrhotic rats have a reduced somatostatinergic tone which can be restored by IGF‐I supplementation, suggesting that somatostatin is the main factor involved in the feed‐back regulation between GH and IGF‐I in cirrhosis.     

Postoperative surveillance with monthly serum tumor markers after living‐donor liver transplantation for hepatocellular carcinoma

Aim: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation decreases patient survival. The usefulness of post‐transplant surveillance with tumor markers, however, is not clear. We evaluated our cumulative experience with recurrent HCC detected during post‐transplant surveillance. Methods: We analyzed 100 patients with HCC detected in the explanted liver. Monthly to bimonthly measurement of tumor markers and yearly computed tomography were scheduled postoperatively. Results: Preoperatively, 82 met the Milan criteria. The histological findings indicated that 61 fulfilled the Milan criteria. In nine patients, HCC recurred 10 months (2–29) after liver transplantation in the graft (n = 1), lung (n = 2), bone (n = 3) and multiple organs (n = 3). In all nine recipients, HCC was first suspected based on an increase in tumor marker levels. Recurrent HCC was confirmed by computed tomography (n = 7) or magnetic resonance imaging (n = 2) within 4 months (0–6) after first identifying an increase in the tumor marker levels. Six cases were treated surgically, two of which achieved prolonged survival of 16 and 38 months. Conclusion: Frequent measurement of α‐fetoprotein and des‐γ carboxy prothrombin was useful for detecting recurrent HCC and may be useful long‐term follow‐up markers for post‐transplant surveillance.     

Significance of quantitative measurement of heparin‐induced platelet antibodies

Background: Heparin‐induced thrombocytopenia (HIT) is a prothrombotic immune‐mediated adverse drug reaction. Antigen and platelet activation assays are used for detection of antibodies. Quantitative results from platelet factor 4 (PF4)‐dependent immunoassays may lead to inter‐laboratory standardization of measurements. Objectives: The aim was to modify a PF4‐dependent immunoassay to measure PF4/heparin antibodies quantitatively. Methods: Over five consecutive years, 1070 samples from thrombocytopenic, heparin‐treated patients were analyzed by a PF4/heparin ELISA and the heparin‐induced platelet activation assay (HIPA). Results of ELISA assay were expressed as arbitrary units per liter (AU/L). Results: Precision of ELISA at the concentration of 50 AU/L was 3.6%. Of 1070 samples, 117 were positive for antibodies by ELISA and/or HIPA assay. The higher the antibody concentration was, the higher was the proportion of HIPA positive cases (>140 AU/L, 100%, n = 26; 100–140 AU/L, 55%, n = 20; 50–99 AU/L, 38%, n = 29; 30–49 AU/L, 17%, n = 36). Conclusions: The measurement of anti‐PF4/heparin antibody concentration is a new parameter that may improve the diagnosis of HIT. All samples with extremely strong antibody concentration were positive also by HIPA. For accuracy, antibody concentrations must be in the linear range of the assay and an international standard is needed.     

188Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation

The addition of radioimmunotherapy to conventional and reduced‐intensity conditioning has been shown to be feasible and effective. Within an ongoing prospective phase II trial, 22 patients with advanced myeloid malignancies and a median age of 65 years (range 54–76) received anti‐CD66 Rhenium radioimmunotherapy followed by fludarabine (150 mg/m²), busulfan (8 mg/kg) and alemtuzumab (75 mg) before allogeneic haematopoietic stem cell transplantation from matched sibling (n = 7) and unrelated donors (n = 15). The extramedullary toxicity in the first 100 d post‐transplantation was limited and all patients engrafted with complete donor chimaerism. The incidence of non‐relapse mortality at day 100 and after 2 years was 4·5% and 23%, respectively. The probability of overall survival at 2 years was 40%. A comparison with a younger historical cohort (median age 57 years) having received the same dose of fludarabine and busulfan but neither radioimmunotherapy nor alemtuzumab showed no difference in outcome. Although the use of alemtuzumab reduced the incidence of acute graft‐versus‐host‐disease, it was associated with a relapse incidence of 40% despite the incorporation of radioimmmunotherapy. In summary, we confirmed the feasibility of combined radioimmunotherapy and reduced‐intensity conditioning in elderly patients. Further optimisation, probably involving less T cell depletion, is necessary before a randomized comparison with standard conditioning can be planned.     

Day treatment group programme for eating disorders: reasons for drop‐out

This study was designed to identify clinical variables and personality factors that could predict the completion or non‐completion of a day treatment group programme for patients with eating disorders. Patients (n = 125) were subdivided into those who had completed a 4‐month day treatment programme (n = 106) and those who had dropped out (n = 19). All the patients had been assessed with regard to eating psychopathology, general psychopathology and personality features at the beginning of the programme. At presentation, 50.4 per cent fulfilled DSM‐IV criteria for anorexia nervosa, 39.2 per cent for bulimia nervosa and 10.4 per cent for an eating disorder not otherwise specified. Non‐completion of therapy was associated with more severe bulimic symptoms, high levels of aggression and extraversion and low levels of inhibitedness. Assessment of these characteristics could be used to improve the therapy programme and to help those patients at increased risk of dropping out. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association.     

Effect of biotherapeutics on cyclosporin‐induced Clostridium difficile infection in mice

Background and Aim: Immunosuppressive therapy may precipitate Clostridium difficile associated disease (CDAD). We evaluated the role of cyclosporin in the development of CDAD in the experimental mouse model and studied the effect of probiotic and epidermal growth factor (EGF) as biotherapeutics measures. Methods: BALB/c mice (n = 24) were divided into four groups. Group I animals not given any inoculum served as controls. Animals in the remaining three groups (Group II, III and IV) were given cyclosporin daily from days 1–7 followed by C. difficile inoculum on day 8. Additionally, the animals received Lactobacillus acidophilus (Group III) and EGF (Group IV) for one‐week post C. difficile challenge. The animals were evaluated for colonization and toxin production by C. difficile, myeloperoxidase (MPO) activity and histopathological changes. Results: Clostridium difficile was colonized and elaborated its toxins in animals receiving cyclosporin and C. difficile. MPO activity was significantly higher (P < 0.05) and histopathological epithelial damage, cryptitis and acute inflammatory changes were seen in the cecum and colon. C. difficile count, toxins A and B titers and MPO activity were significantly lowered (P < 0.05) in animals receiving probiotic and EGF. Histopathologically, mucodepletion and inflammatory infiltrate were decreased in the biotherapeutic receiving animals. Conclusions: Cyclosporin led to the development of mild to moderate CDAD in animals. Administration of biotherapeutics reduced the severity of CDAD. Future clinical trials are needed for further investigation of these potential biotherapeutic measures.     

Compartmentalization and its implication for peripheral immunologically‐competent cells to the liver in patients with HBV‐related acute‐on‐chronic liver failure

Aims: This study attempts to characterize the feature of immunologically competent cells (ICCs) and evaluate its clinical implication in patients with acute‐on‐chronic liver failure (ACLF) in relation to chronic hepatitis B virus (HBV) infection. Methods: Circulating ICCs were examined in ACLF patients (n = 75), as well as in patients with hepatitis B (CHB, n = 31), CHB‐related liver cirrhosis (LC, n = 36), and normal controls (NC, n = 30). Intrahepatic ICCs in some patients were further analyzed via immunohistochemical and flow cytometric assays. Results: Total lymphocytes, CD4⁺ T cells, CD8⁺ T cells, and NK cells in circulation were numerically lower in the ACLF and LC groups compared to the CHB and NC groups. Importantly, the number of these cells was significantly lower in non‐surviving ACLF patients compared with surviving ACLF patients. In comparison to NC, ACLF patients displayed a significantly higher ratio of liver‐infiltrating CD4⁺ T‐cell frequency than its circulating counterpart, suggesting that the possiblility of the ICCs compartmentalization from the peripheral blood into the liver in ACLF. Immunohistochemical analysis showed that intrahepatic CD4⁺ cells, CD8⁺ cells, and CD56⁺ cells were significantly higher in the ACLF group compared with the other three groups, suggesting a stronger cellular immune response‐mediated inflammation in ACLF group than other patient groups. Conclusions: The abnormal prevalence of circulating and intrahepatic ICCs possibly acts as an important factor that may drive the progression of HBV‐related ACLF.     

High-intensity focused ultrasound ablation:An effective bridging therapy for hepatocellular carcinoma patients

AIM:To analyze whether high-intensity focused ultrasound(HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma(HCC).METHODS:From January 2007 to December 2010,49 consecutive HCC patients were listed for liver transplantation(UCSF criteria).The median waiting time for transplantation was 9.5 mo.Twenty-nine patients received transarterial chemoembolization(TACE) as a bringing therapy and 16 patients received no treatment before transplantation.Five patients received HIFU ablation as a bridging therapy.Another five patients with the same tumor staging(within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison.Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores,tumor size and number,and cause of cirrhosis.RESULTS:The HIFU group and TACE group showed no difference in terms of tumor size and tumor number.One patient in the HIFU group and no patient in the TACE group had gross ascites.The median hospital stay was 1 d(range,1-21 d) in the TACE group and two days(range,1-9 d) in the HIFU group(P < 0.000).No HIFU-related complication occurred.In the HIFU group,nine patients(90%) had complete response and one patient(10%) had partial response to the treatment.In the TACE group,only one patient(3%) had response to the treatment while 14 patients(48%) had stable disease and 14 patients(48%) had progressive disease(P = 0.00).Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list(P = 0.559).CONCLUSION:HIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis.It may reduce the drop-out rate of liver transplant candidate.     

Inferior outcome after allogeneic transplant in first remission in high‐risk AML patients who required more than two cycles of induction therapy

While some patients with high‐risk acute myeloid leukemia (AML) require one or two cycles of induction chemotherapy to achieve a complete remission (CR), others require more than two cycles. We examined the outcomes of patients with high‐risk AML who received allogeneic HPC transplant in CR1. Forty five consecutive high‐risk AML patients in CR1 were included. All 45 patients had adverse cytogenetics, FLT 3 mutations, or secondary AML. Group A patients (n = 33) received one or two cycles, and Group B (n = 12) three or more cycles of induction chemotherapy. The patients were comparable in age, sex, white cell count at presentation, and time from diagnosis and from last chemotherapy to transplant. The 100‐day mortality rate was higher in Group B patients (50% vs. 9%, P = 0.006). They had a higher non‐relapse mortality (33% vs. 6%, P = 0.035) and a longer length of hospital stay from the day of stem cell infusion (median 21 vs. 20, P = 0.02; third quartile 22 vs. 28, P = 0.02). There was also a trend toward inferior event‐free survival and overall survival. High‐risk AML patients undergoing allogeneic transplant in CR1 after three or more cycles of induction chemotherapy have an inferior outcome and higher mortality when compared to those who only needed one or two cycles of induction chemotherapy. Novel strategies are needed to reduce the transplant‐related mortality in high‐risk AML patients needing more than two cycles of induction chemotherapy prior to allogeneic transplant in CR1. Am. J. Hematol. 90:715–718, 2015. © 2015 Wiley Periodicals, Inc.     

Radial versus femoral approach for same‐day inter‐facility transfer for percutaneous coronary intervention

Background

The use of radial approach for coronary angiography, followed by same‐day inter‐facility transfer for percutaneous coronary intervention (PCI) has not yet been evaluated.

Objectives

We sought to assess the safety and feasibility of using the transradial as compared to the transfemoral approach in patients undergoing diagnostic angiogram with same‐day transfer to a PCI facility.

Methods

Patients that underwent diagnostic coronary angiography between January 2011 and June 2017 in a referring facility, and were transferred for same‐day PCI were included. Patients’ demographics, as well as procedural data and in‐hospital outcome, were collected.

Results

Three hundred fifty‐two participants were included. Of these, 36 (10.2%) patients received transradial access. Patients in the transradial group were older (68 ± 10 vs 62 ± 12 years, P = 0.007), and received a significantly higher total dose of heparin including both, diagnostic and PCI procedures (5935 ± 1865 vs 10029 ± 2771 units, P < 0.001). None of the transradial patients experienced bleeding or access‐related complications. In the transfemoral group, 9 (3%) vascular‐access complications were recorded. Contrast volume was lower for transradial patients (177 ± 47 vs 216 ± 75 mL, P < 0.001). A higher proportion of outpatients were discharged from the PCI‐center the same day after transradial procedures (53% vs 1.3%, P < 0.001).

Conclusions

Transradial access for inter‐facility transfer for PCI after diagnostic angiogram appears safe and feasible, without increasing the risk for ischemic hand complications. Transradial access was associated with fewer bleeding and vascular access‐site complications, and with a higher likelihood for a same‐day discharge home in outpatients.     

Comparison of three‐year clinical outcomes between sirolimus‐versus paclitaxel‐eluting stents in diabetic patients: Prospective randomized multicenter trial

Background : Three‐year follow‐up of major adverse cardiovascular event (MACE) (death, nonfatal myocardial infarction, target lesion revascularization) and the predictors of MACEs in diabetic patients after sirolimus‐eluting stent (SES) or paclitaxel‐eluting stent (PES) implantation have not been reported. Methods : Diabetic patients with de novo coronary lesions (169 patients with 190 lesions) were randomly assigned prospectively to either SES or PES. Results : Baseline characteristics were similar between the two groups. The rates of MACEs [5.9% (n = 5) in the SES vs. 9.5% (n = 8) in the PES Group, P = 0.374] and definite stent thrombosis [1.2% (n = 1) in the SES vs. 3.6% (n = 3) in the PES Group, P = 0.368] were similar in the two groups during the three‐year follow‐up. Multivariate logistic analysis showed that insulin treatment was the only independent predictor of MACE [odds ratio (OR) 8.60, 95% confidence interval (CI) 3.25–22.76, P < 0.001] and target vessel revascularization (TVR) (OR 9.50, 95% CI 3.07–29.44, P < 0.001) during the three‐year follow‐up. Conclusions : The rates of MACEs, TVR, and stent thrombosis during the three‐year follow‐up were similar in the SES and PES Groups. Insulin treatment was a main predictor of MACEs and TVR during the three‐year follow‐up after either SES or PES implantation. © 2009 Wiley‐Liss, Inc.     

Efficacy of chemotherapy or chemo‐anti‐PD‐1 combination after failed anti‐PD‐1 therapy for relapsed and refractory hodgkin lymphoma: A series from lysa centers

Anti‐PD‐1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti‐PD‐1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti‐PD‐1 therapy, assessed by PET‐CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pretreated before anti‐PD‐1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti‐PD1 therapy were progressive disease (PD) (n = 24) and partial response (PR) (n = 6). For the 24 PD patients, median anti‐PD‐1 related PFS was 7.5 months (95%CI, 5.7‐11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti‐PD‐1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow‐up of 12.1 months (7‐14.7), the median PFS following the initiation of CT was 11 months (95% CI 6.3‐not reached) and the median of overall survival was not reached. These observations in highly pretreated HL patients suggest that anti‐PD‐1 therapy might re‐sensitize tumor cells to CT.