Tacrolimus with Mycophenolate Mofetil (MMF) or Sirolimus vs. Cyclosporine with MMF in Cardiac Transplant Patients: 1-Year Report

The most advantageous combination of immunosuppressive agents for cardiac transplant recipients has not yet been established. Between November 2001 and June 2003, 343 de novo cardiac transplant recipients were randomized to receive steroids and either tacrolimus (TAC) + sirolimus (SRL), TAC + mycophenolate mofetil (MMF) or cyclosporine (CYA) + MMF. Antilymphocyte induction therapy was allowed for up to 5 days. The primary endpoint of >/=3A rejection or hemodynamic compromise rejection requiring treatment showed no significant difference at 6 months (TAC/MMF 22.4%, TAC/SRL 24.3%, CYA/MMF 31.6%, p = 0.271) and 1 year (p = 0.056), but it was significantly lower in the TAC/MMF group when compared only to the CYA/MMF group at 1 year (23.4% vs. 36.8%; p = 0.029). Differences in the incidence of any treated rejection were significant (TAC/SRL = 35%, TAC/MMF = 42%, CYA/MMF = 59%; p < 0.001), as were median levels of serum creatinine (TAC/SRL = 1.5 mg/dL, TAC/MMF = 1.3 mg/dL, CYA/MMF = 1.5 mg/dL; p = 0.032) and triglycerides (TAC/SRL = 162 mg/dL, TAC/MMF = 126 mg/dL, CYA/MMF = 154 mg/dL; p = 0.028). The TAC/SRL group encountered fewer viral infections but more fungal infections and impaired wound healing. These secondary endpoints suggest that the TAC/MMF combination appears to offer more advantages than TAC/SRL or CYA/MMF in cardiac transplant patients, including fewer >/=3A rejections or hemodynamic compromise rejections and an improved side-effect profile.     

Relevance of inflammatory cell infiltrates for complete atrioventricular block in experimental murine myocarditis.

BACKGROUND: There are few systemic pathologic studies on myocarditis. This study aimed to clarify the pathologic characteristics of murine myocarditis. METHODS: We recorded serial electrocardiograms in experimental viral myocarditis in mice and then examined their cardiac pathology. After taking baseline electrocardiograms, we inoculated the mice intraperitoneally with the encephalomyocarditis virus. Electrocardiograms were serially recorded until 220 days after the virus inoculation. RESULTS: Serial electrocardiograms revealed ectopic beats, low voltage of the QRS complex, and the appearance of complete atrioventricular (AV) block. Corresponding myocardial lesions were found in the hearts of mice with these ectopic beats. Mononuclear cell infiltrations into the His bundle were most frequently found in mice with complete AV block. CONCLUSIONS: Inflammatory change with cellular infiltrations was the most common pathologic finding in mice with complete AV block. In clinical settings, anti-inflammatory therapy might be recommended for patients with myocarditis complicated with conduction disturbances.     

Case of ruptured gastroduodenal arterial pseudoaneurysm with penetration to the duodenum, successfully treated with transcatheter arterial embolization]

A 77-year-old man, who underwent segmental pancreatectomy for intraductal papillary mucinous adenoma in 2001, was referred to our hospital with complaints of hematemesis and melena on January, 2004. Emergency upper gastrointestinal endoscopy showed a pulsating submucosal protrusion in the duodenal bulb, which was identified as a gastroduodenal arterial aneurysm measuring 1.5cm on abdominal CT imaging. Transcatheter arterial embolization of the aneurysm with metallic coils was successfully performed. Periodically repeated endoscopic examination has revealed the coils protruding into the duodenal lumen without any serious complication.     

Recent trends in early outcome of adult patients after heart transplantation: a single-institution review of 251 transplants using standard donor organs.

Older age, prior transplantation, pulmonary hypertension, and mechanical support are commonly seen in current potential cardiac transplant recipients. Transplants in 436 consecutive adult patients from 1994 to 1999 were reviewed. There were 251 using standard donors in 243 patients (age range 18-69 years). To emphasize recipient risk, 185 patients who received a nonstandard donor were excluded from analysis. The indications for transplant were ischemic heart disease (n = 123, 47%), dilated cardiomyopathy (n = 82, 32%), and others (n=56, 21%). One hundred and forty-nine (57%) recipients were listed as status I; 5 and 6% were supported with an intra-aortic balloon and an assist device, respectively. The 30-d survival and survival to discharge were 94.7 and 92.7%, respectively; 1-year survival was 89.1%. Causes of early death were graft failure (n = 6), infection (n = 4), stroke (n = 4), multiorgan failure (n = 3) and rejection (n = 2). Predictors were balloon pump use alone (OR= 11.4, p =0.002), pulmonary vascular resistance > 4 Wood units (OR = 5.7, p = 0.007), pretransplant creatinine > 2.0 mg/dL (OR = 6.9, p = 0.004) and female donor (OR = 8.3, p = 0.002). Recipient age and previous surgery did not affect short-term survival. Heart transplantation in the current era consistently offers excellent early and 1-year survival for well-selected recipients receiving standard donors. Early mortality tends to reflect graft failure while hospital mortality may be more indicative of recipient selection.     

Dietary nucleic acid and intestinal microbiota synergistically promote a shift in the Th1/Th2 balance toward Th1-skewed immunity

BACKGROUND: Intestinal microbiota are known to play an important role in the establishment of oral tolerance, thereby protecting the organism from food allergies. Dietary intake of nucleic acid (NA) is also reported to have such an anti-allergic effect; however, one unsolved question is whether or not dietary NA would act through a process of toll-like receptor 9 signaling activated by DNA containing a CpG motif, a well-known sequence leading to immunostimulatory activity. In this study, we focused on the question of whether the addition of dietary NA lacking CpG motifs would allow continued modulation of the Th1/Th2 balance. METHODS: Germ free (GF) and Bifidobacterium-infantis-monoassociated BALB/c mice were maintained on either an NA-free casein diet or on an NA-supplemented casein diet for 4 weeks. Thereafter, both the in vivo anti-casein antibody levels and in vitro splenocyte cytokine secretion pattern were evaluated. RESULTS: Feeding with a casein diet elicited a substantial increase in the serum anti-casein-specific IgG1, IgG2a, and IgE levels of GF mice fed the NA free-diet. The in vitro cytokine production profile showed that enhanced IL-4 production in the GF mice fed the NA free-diet was markedly reduced by the supplementation with dietary NA in both the GF and B.-infantis-monoassociated mice. In addition, IFN-gamma secretion increased in the B.-infantis-reconstituted mice fed the diet containing NA. CONCLUSIONS: These results suggest that dietary intake of NA devoid of CpG motifs may prevent the development of allergies via acceleration of Th1-dominant immunity.     

Peroxyl radical scavenging capability of fish sauces measured by the chemiluminescence method

Oxygen-related free radicals have been suggested as a cause of aging and various diseases, for example, various cancers and rheumatoid arthritis. A radical scavenger as an antioxidant has been sought in foods. Fish sauces are traditional Asian fermented seasonings. Using the luminol chemiluminescence method, the peroxyl radical scavenging capability of fish sauces was examined. From the IC50 values, many fish sauces have been shown to have a strong scavenging capability as well as soy sauces. A scavenging mechanism is also proposed.     

Dual functions of Runx proteins for reactivating CD8 and silencing CD4 at the commitment process into CD8 thymocytes

To understand how CD8 expression is regulated during the transition process from CD4+8+ (CD4 and CD8 double positive, DP) to CD4-8+ (CD8 single positive, CD8SP) cells in the thymus, the involvement of Runx proteins in the alteration of chromatin configuration was investigated. Using the chromatin immunoprecipitation assay, we first demonstrated that Runx proteins bind to the stage-specific CD8 enhancer, as well as the CD4 silencer, in CD8SP thymocytes. Among Runx family members, Runx3 expression was initiated in DP thymocytes receiving a positive selection signal and increased in concert with differentiation to the CD8SP stage. Furthermore, reactivation of the CD8 gene, as well as CD4 silencing, was suppressed in positively selected thymocytes of Runx dominant-negative transgenic mice. These results suggest that Runx proteins, especially Runx3, are involved in lineage specification of CD8 T cells and provide important information for understanding the mechanism for the mutually exclusive expression of coreceptors in mature thymocytes.     

Nutritional Assessment in Adult Patients with Dysphagia: A Scoping Review

Malnutrition negatively affects the quality of life of patients with dysphagia. Despite the need for nutritional status assessment in patients with dysphagia, standard, effective nutritional assessments are not yet available, and the identification of optimal nutritional assessment items for patients with dysphagia is inadequate. We conducted a scoping review of the use of nutritional assessment items in adult patients with oropharyngeal and esophageal dysphagia. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched to identify articles published in English within the last 30 years. Twenty-two studies met the inclusion criteria. Seven nutritional assessment categories were identified: body mass index (BMI), nutritional screening tool, anthropometric measurements, body composition, dietary assessment, blood biomarkers, and other. BMI and albumin were more commonly assessed in adults. The Global Leadership Initiative on Malnutrition (GLIM), defining new diagnostic criteria for malnutrition, includes the categories of BMI, nutritional screening tool, anthropometric measurements, body composition, and dietary assessment as its required components, but not the blood biomarkers and the “other” categories. We recommend assessing nutritional status, including GLIM criteria, in adult patients with dysphagia. This would standardize nutritional assessments in patients with dysphagia and allow future global comparisons of the prevalence and outcomes of malnutrition, as well as of appropriate interventions.     

Heart Transplantation for Giant Cell Myocarditis: A Case Series

BackgroundGiant cell myocarditis (GCM) has a poor prognosis without heart transplant, but post-transplant survival is unknown.PurposeTo describe the post-transplant survival of patients with GCM at a large transplant center.MethodsSeven patients underwent heart transplant for histologically confirmed GCM of the explanted heart. The median age was 59 years, and 43% (3 of 7) were female. All patients had cardiogenic shock, multiorgan failure, elevated troponin, and recurrent ventricular tachycardia, and some required mechanical circulatory support. All patients received rabbit antithymocyte globulin (rATG) in the perioperative period at a dose of 1.5 mg/kg daily for 1 to 5 days and 4 received intravenous immunoglobulin 1 g/kg daily for 2 days after rATG. All patients had early initiation of tacrolimus by first to third postoperative day depending on renal function, early mycophenolate, and high dose steroid. All were maintained using tacrolimus, mycophenolate, and prednisone.ResultsOne patient had asymptomatic recurrence of GCM at 3 months, managed by up-titration of tacrolimus, and had asymptomatic 2R cellular rejection at 4 months, managed with steroid bolus. No patient had high-grade rejection. One patient died at 267 days, possibly of GCM. Six of 7 (86%) remain alive at a median of 842 days (2.3 years) post transplant.ConclusionsPatients with GCM have excellent post-transplant survival with use of rATG and triple drug immunosuppressive therapy; however, some patients remain at risk for GCM recurrence after transplant, which may respond to augmented immunosuppression.