Evaluation of salvaged myocardium after acute myocardial infarction using single photon emission computed tomography after 201Tl-glucose-insulin infusion.

BACKGROUND: GIK-201Tl imaging reportedly improves the detection of viable myocardium, so the present study evaluated whether it can detect myocardial viability after acute myocardial infarction (AMI). METHODS AND RESULTS: Resting 201Tl and 99mTc-pyrophosphate (PYP) dual single photon emission computed tomography (SPECT) and 201Tl SPECT after 201Tl with GIK (10% glucose, insulin 5 U, and KCl 10 mmol) infusion (GIK-201Tl) were performed in 25 AMI patients within 10 days of admission. GIK-201Tl SPECT images were obtained immediately and 4 h after infusion. Left ventriculography (LVG) was performed within 3 weeks and at 6 months when follow-up 201Tl SPECT was also performed. From 20 SPECT segments, both the summed defect score (RDS) and the number of defect segments (ES) were calculated. The infarcted area was defined as 99mTc-PYP uptake segments. Wall motion was estimated in 7 LVG segments. The ES of R-201Tl (5.5 +/- 2.8), immediate GIK-201Tl (4.0 +/- 2.3), and 4-h GIK-201Tl (5.6 +/- 2.7) were lower than that of 99mTc-PYP (7.5 +/- 4.1) (p<0.05), and the ES had significantly declined 6 months later on 201Tl (3.5 +/- 2.8) (p<0.05). Although the RDS of R-201Tl (11.3 +/- 7.9) and 4-h GIK-201Tl (11.2 +/- 6.3) were greater than at the 6-month 201Tl (7.1 +/- 6.5), immediate GIK-201Tl (7.4 +/- 6.5) was equivalent to follow-up 201Tl. The sensitivity of immediate GIK-201Tl was highest among the imaging methods. CONCLUSION: To detect myocardial viability after AMI, early imaging with GIK-201Tl is more useful than resting 201Tl imaging.     

Lipoteichoic acid may affect the pathogenesis of PBC-like bile duct damage and might be involved in systemic multifocal epithelial inflammations in chronic colitis-harboring TCRα−/−×AIM−/− mice

Background: Chronic colitis-harboring TCRα^{? / ?} × AIM^{? / ?} mice showed PBC-like bile duct damage in the liver. Bacterial infection is one of the candidates for the pathogenesis of PBC. We demonstrated that the bacterial cell wall component lipotheicoic acid (LTA) was detected at sites of inflammation around damaged bile ducts in PBC patients. The aim of this study was to investigate the pathophysiology of the liver and other organs in TCRα^{? / ?} × AIM^{? / ?} mice.

Methods: Thirteen female TCRα^{? / ?} × AIM^{? / ?} mice were sacrificed at 24 weeks of age. The liver, stomach, small intestine, colon, pancreas, kidney and spleen were studied for pathological examination. Using anti-LTA antibody as the primary antibody, an immunohistochemical study was carried out.

Results: In the liver, LTA was mainly detected in the portal area with inflammation, and some of the cytoplasm of hepatocytes. Inflammations were also observed in the stomach, intestine, pancreas and kidney. Throughout the gastrointestinal tract, from the stomach to the colon, LTA was detected in the epithelium at sites of inflammation. Furthermore, LTA was detected around both pancreatic ducts with inflammation and distal renal tubules with inflammation.

Conclusions: The development of inflammations in the liver as well as extensive organs, strongly suggests a close relationship between bile duct damage and systemic multifocal epithelial inflammations, perhaps involving bacterial LTA, in TCRα^{? / ?} × AIM^{? / ?} mice.     

Lipoteichoic acid may affect the pathogenesis of bile duct damage in primary biliary cirrhosis

Aim: Intrahepatic bile ducts are the targets for inflammation in primary biliary cirrhosis (PBC), but their pathogenesis is not known. Gram-positive bacterial DNA was detected recently in gallbladder bile of PBC patients. In the present study, we assessed the possible pathological role of lipoteichoic acid (LTA), the Gram-positive bacterial cell wall component, in PBC.

Methods: Liver samples, obtained from 20 patients with PBC (stage 1–2 with CNSDC: stage 3–4 with loss of bile ducts = 10:10) and from 13 patients with chronic hepatitis due to hepatitis C virus (CH–C) with lymphocytic cholangitis, were subjected to immunohistochemical staining with polyclonal rabbit anti-LTA as the primary antibody. Serum reactivities to LTA were studied by ELISA. After 1 μg of purified LTA was placed in a 96-well microplate as an antigen, an antibody capture assay was carried out using serum samples from PBC (n = 20), CH–C (n = 13) and healthy subjects (n = 11).

Results: LTA was localized around the sites of chronic non-suppurative destructive cholangitis (CNSDC) in the portal area in stage 1–2 PBC but was not detected in the portal area in CH–C. In stage 3–4 PBC, LTA was localized around sites of ductular proliferation at the periphery of portal tracts. IgM class anti-LTA serum titers were significantly higher in PBC than in CH–C. IgA class anti-LTA serum titers were significantly higher in PBC than in healthy subjects.

Conclusions: In the PBC livers, the profile of immunoreactivity to LTA changed markedly as the disease progressed. Sera from PBC showed higher levels of anti-LTA titers than CH–C (IgM) or from healthy subjects (IgA). The LTA-mediated immune system might affect the initiation and/or progression of PBC.     

Long-term outcome of complete cardiovascular implantable electronic device removal with cardiopulmonary bypass

Definitive endovascular techniques have been developed for pacemaker lead extraction; however, a few patients require immediate secondary open heart surgery because of incomplete transvenous lead extraction. This study examined the safety, effectiveness, and long-term outcome of the removal of cardiovascular implantable electronic device (CIED) via median sternotomy under cardiopulmonary bypass. The removal of CIED was performed in 6 patients (mean age 57 ± 16 years, 5 males and 1 female), from September 2000 to April 2011. The reasons for removal included eradication of an infection in 5 patients and elimination of pacemaker component allergy in 1. Positive culture results, including methicillin-sensitive Staphylococcus aureus (MSSA, n = 2), methicillin-resistant S. aureus (MRSA, n = 1), coagulase-negative staphylococci (CNS, n = 1), and methicillin-resistant S. epidermidis (MRSE, n = 1) were observed in all 5 infected patients. Mitral annuloplasty (n = 1), mitral valvuloplasty (n = 1), tricuspid annuloplasty (n = 3). Implantation of myocardial pacing leads (n = 5) were performed concomitantly (n = 4), or secondarily (n = 1). All 6 patients were alive in good condition at 72 ± 55 months following CIED removal. New device infection occurred in 1 patient during long-term follow up. Complete surgical removal of pacing systems via median sternotomy with cardiopulmonary bypass is, therefore, considered to be safe and feasible with acceptable long term results.     

Successful bridge therapy of gilteritinib to cord blood transplantation in relapsed acute myeloid leukemia after bone marrow transplantation

The FMS-related tyrosine kinase 3 (FLT3) internal tandem duplication mutations (FLT3-ITD) positive acute myeloid leukemia (AML) is a disease with a dismal outcome. Gilteritinib is a second-generation FLT3 inhibitor with activity against ITD and high affinity toward the FLT3 receptor, thereby showing therapeutic potential for relapsed/refractory FLT3-mutated AML. Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA) identical sibling donor was performed in a 38-year-old Japanese male with FLT3-ITD positive AML. Neutrophil engraftment (>0.5 × 10⁹/L) was achieved on day 16, and bone marrow remission was revealed on day 32. The patient's AML relapsed hematologically four months after BMT and was resistant to salvage chemotherapy. Gilteritinib was administered and the patient achieved non-remission but ‘stable disease’ status according to the response criteria. During administration, liver damage was observed but controllable. The patient received cord blood transplantation (CBT) as the second hematopoietic stem cell transplantation (HSCT) three months after relapse and achieved second remission. There was no evidence of recurrence of AML four months after CBT. This case demonstrates that gilteritinib can control FLT3-ITD positive AML that relapsed early after initial HSCT and can bridge to second HSCT.