A case of paracoccidioidomycosis with severe adrenal insufficiency

Paracoccidioidomycosis (PCM) is the most common systemic fungal disease in central-south America, but is rare in Japan. We experiensed a case of PCM in a patient, who came from Bolivia and presented with mouth pain and reduced dietary intake but no fever. Adrenal insufficiency was diagnosed with extremely high serum adrenocorticotropic hormone (ACTH) and was resolved with hormone supplementation. The PCM was treated with trimethoprim-sulfamethoxazole which was switched to itraconazole and improvement was achieved.     

Comparison of short- and long-term outcomes after early versus late liver retransplantation: a single-center experience

Background

As the survival of patients after liver transplantation (LT) improves, the requirement of liver retransplantation (reLT) for late graft failure has grown. Although some have reported that the short-term outcome of late reLT was comparable with that of early reLT, it remains unknown whether long-term survival of late reLT is inferior to that of early reLT patients.

Materials and methods

We reviewed early (<6 mo after primary LT) and late (≥6 mo after primary LT) reLT cases performed between January 2000 and December 2010.

Results

Sixteen early and 32 late reLT cases were analyzed. There was no significant difference regarding the number of units of red blood cells transfused during the transplantation between the groups, whereas operative time was significantly longer in the late reLT cases. Graft loss within 3 mo after early and late reLT was 18.6% and 15.6%, respectively. Patient and graft survival rates after 1, 3, 5, and 10 y in the late reLT group were 80.6%, 73.3%, 73.3%, and 67.7% and 80.7%, 69.1%, 63.3%, and 54.3%, respectively, whereas those in the early reLT group were 75.0%, 75.0%, 64.3%, and 64.3% and 81.3%, 75.0%, 64.3%, and 32.1%, respectively. There was no significant difference in patient or graft survival rates between the groups (P = 0.91 and 0.91, respectively).

Conclusions

Acceptable short- and long-term survival were provided in early and late reLT. The time between the primary LT and reLT does not seem to play significant role in the prognosis of reLT in the long term.     

Fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation

T. Mori, Y. Nakamura, J. Kato, K. Sugita, M. Murata, K. Kamei, S. Okamoto. Fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation.
Transpl Infect Dis 2011. All rights reserved Abstract: Rhodotorula species have been increasingly recognized as emerging pathogens, particularly in immunocompromised patients. We herein report on a patient with myelodysplastic syndrome who developed fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. He developed severe acute graft‐versus‐host disease requiring high‐dose steroids, and had serially been administered fluconazole and micafungin for the prophylaxis of fungal infection. Although several cases of Rhodotorula infection after HSCT have been reported, all of them were recipients of autologous HSCT, not allogeneic HSCT. A review of all the reported cases of Rhodotorula infection after HSCT revealed that all patients had received fluconazole or echinocandins before the onset of infection. The findings suggest that Rhodotorula species could be causative yeasts, particularly in patients receiving fluconazole or echinocandins, both of which are inactive against the species.     

Phase I clinical trial of vaccination with URLC10-derived peptide for patients with advanced esophageal cancer

Background

Up-regulated gene in lung cancer 10 (URLC10), confirmed to be lymphocyte antigen 6 complex locus K and defined as an oncoantigen, has been identified as a tumor-associated antigen by systematic analysis of expression levels of thousands of genes in lung cancer tissues and esophageal squamous cell carcinoma tissues, which were compared with those of normal human tissues by use of cDNA microarray analysis. Human leukocyte antigen (HLA)-A*2402-positive dendritic cells pulsed with URLC10-derived epitope peptide induced CD8⁺ cytotoxic T lymphocytes to exert specific cytotoxicity against the HLA-A*2402-positive URLC10-expressing esophageal carcinoma cell lines.

Methods

In a phase I clinical trial we evaluated the safety and immunogenicity of a URLC10-177 peptide vaccine emulsified with Montanide ISA51 for patients with unresectable advanced esophageal cancer. One milligram of URLC10-177 peptide in 1 mL sterile saline was emulsified with 1 mL incomplete Freund’s adjuvant and administered subcutaneously to the inguinal region or axilla of the patients. One course of treatment comprised four vaccinations, which were performed every week in the first and second treatment courses and subsequently every 2 weeks after the first vaccination in the third treatment course.

Results

Redness and induration of the skin were the only adverse events at the injection site and were believed to be a delayed-type hypersensitivity (DTH) reaction against the peptide vaccine. A URLC10-177-specific immune reaction in the enzyme-linked immunospot assay was detected in three of four DTH-positive patients (75 %) and in one of three DTH-negative patients (33 %). Furthermore, patients who had a DTH reaction seemed to survive longer than those who had no DTH reaction.

Conclusion

URLC10-177 peptide/Montanide vaccine therapy was well tolerated and induced a URLC10-177 peptide-specific immune response. Therapeutic URLC10-177 peptide vaccination is expected to have clinical benefit in prolonging the survival of patients with unresectable advanced esophageal cancer.     

Impact of glutathione S-transferase T1 gene polymorphisms on acute cellular rejection in living donor liver transplantation

It has previously been demonstrated that glutathione S-transferase T1 (GSTT1) genetic mismatch between recipient and donor is a risk factor for developing immune-mediated hepatitis following liver transplantation and for antibody-mediated rejection in renal transplantation. Little is known whether the GSTT1 gene polymorphism affects the incidence of acute cellular rejection (ACR) following living donor liver transplantation (LDLT). Patients underwent LDLT at Nagoya University or Kyoto University, Japan, between 2004 and 2009. Genotyping of GSTT1 genes (null or present genotype) was conducted in recipients and donors. A total of 155 LDLT cases were examined. Forty-seven recipients (30.3%) developed early ACR. There was no association of recipient GSTT1 genotype with ACR incidence. However, ACR incidence was significantly higher in recipients transplanted from GSTT1 present genotype donors than in those transplanted from GSTT1 null genotype donors [odds ratio (OR) = 2.64, 95% confidence interval (CI) = 1.12–5.83, p = 0.016]. Moreover, GSTT1 recipient/donor genotype mismatch (present/null or null/present) was significantly associated with ACR development (OR = 2.28, 95% CI = 1.12–4.61, p = 0.022). The genotyping of GSTT1 in recipients and donors might be useful to stratify the liver transplant recipients according to risk of ACR.     

In vivo bioluminescence imaging of magnetically targeted bone marrow‐derived mesenchymal stem cells in skeletal muscle injury model

The purpose of this study is to clarify the kinetics of transplanted mesenchymal stem cells (MSCs) in rat skeletal muscle injury model and the contribution of the magnetic cell delivery system to muscle injury repair. A magnetic field generator was used to apply an external magnetic force to the injury site of the tibia anterior muscle, and 1 × 10⁶ MSCs labeled with ferucarbotran–protamine complexes, which were isolated from luciferase transgenic rats, were injected into the injury site. MSCs were injected with and without an external magnetic force (MSC M+ and MSC M? groups, respectively), and phosphate‐buffered saline was injected into injury sites as a control. In vivo bioluminescence imaging was performed immediately after the transplantation and, at 12, 24, and 72 h, and 1 and 4 weeks post‐transplantation. Also, muscle regeneration and function were histologically and electromechanically evaluated. In vivo bioluminescence imaging showed that the photon of the MSC M+ group was significantly higher than that of the MSC M? group throughout the observation period. In addition, muscle regeneration and function in the MSC M+ group was histologically and functionally better than that of the MSC M? group. The results of our study indicated that magnetic cell delivery system may be of use in directing the transplanted MSCs to the injury site to promote skeletal muscle regeneration. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 754–759, 2013     

Atypical Pneumocystis jiroveci pneumonia with multiple nodular granulomas after rituximab for refractory nephrotic syndrome

Background

Rituximab, an anti-CD20 antibody that targets B cells, is a promising agent against steroid-dependent and steroid-resistant nephrotic syndrome in children.

Case-Diagnosis/Treatment

We report a 3-year-old boy who presented with atypical Pneumocystis jiroveci pneumonia (PCP) following administration of rituximab for refractory nephrotic syndrome. He had received cyclosporine and daily prednisolone for over 1?year. Following rituximab therapy, a hazy shadow was observed on his chest X-ray. Chest-computed tomography revealed multiple nodular lesions in bilateral lungs, although his clinical symptoms were subtle. PCR analysis demonstrated the presence of Pneumocystis DNA in his bronchoalveolar lavage. Lung wedge resection of the nodular lesion exhibited granulomas containing a few cysts of P. jiroveci that primarily consisted of T cells and histiocytes and lacked B cells. A deficiency of B cells following rituximab treatment suggests a dramatic effect on the immune response and, therefore, could result in granulomatous PCP. Nodular granulomatous lesions of PCP comprise an emerging concept previously reported in adults with hematological disease, bone marrow transplant, or treatment with rituximab. We report the first pediatric case of nodular PCP. Granulomatous PCP can be life-threatening. Moreover, bronchoalveolar lavage often fails to demonstrate the presence of P. jiroveci DNA. Wedge biopsy is warranted for definitive diagnosis. Our patient fully recovered with sulfamethoxazole/trimethoprim treatment because of early detection.

Conclusions

The indication of rituximab for refractory nephrotic syndrome has increased recently. Therefore, recognition of the risk of atypical PCP is important. Our findings suggest that PCP prophylaxis should be considered following rituximab therapy.     

Uncemented third-generation ceramic-on-ceramic total hip arthroplasty using metal acetabular shell with direct taper locking liner

Background

The ceramic-on-ceramic (CoC)-bearing couple in total hip arthroplasty (THA) was developed to reduce the wear debris and osteolysis. Although the mechanical strength of third-generation ceramic has improved over previous generations, the risk of osteolysis and ceramic fracture is still an important concern.

Methods

We studied 124 uncemented THAs with third-generation CoC-bearing couple implanted between 2000 and 2004. The ceramic liner and head were secured with the direct taper locking mechanism. One hundred and eleven hips were followed-up for minimum of 8 years, with an average follow-up period of 10.1 years (range 8.0–12.8 years). Patients were evaluated with a particular emphasis on the prevalence of the osteolysis and the ceramic fracture.

Results

The survivorship with the end point as implant revision for any reason was 94.9 % (95 % confidence intervals 90.0–99.3 %) at 12.8 years. Revisions were performed because of one ceramic liner fracture, three dislocations, and two deep infections. No radiographic evidence of wear or osteolysis was observed. The preoperative Merle d’Aubigne and Postel hip score increased from 11.6 to 17.1.

Conclusions

Patients, who received third-generation CoC THA had no detectable wear and osteolysis. One ceramic fracture occurred, and the main reason for revision was dislocation.     

Comparison of Billroth I and Roux-en-Y Reconstruction after Distal Gastrectomy for Gastric Cancer: One-year Postoperative Effects Assessed by a Multi-institutional RCT

Purpose

This randomized, controlled trial evaluated the clinical efficacy of Billroth I (BI) and Roux-en-Y (RY) reconstruction at 1 year after distal gastrectomy for gastric cancer.

Methods

The primary end point was the amount of body weight lost at 1 postoperative year, and secondary end points included other items related to nutritional status such as serum albumin and lymphocyte count, as well as endoscopic examination findings of the remnant stomach and esophagus. Of the 332 patients enrolled, 163 were assigned to the BI group and 169 were randomized to the RY group.

Results

The loss in body weight 1 year after surgery did not differ significantly between the BI and RY groups (9.1 % and 9.7 %, respectively, p = 0.39). There were no significant differences in other aspects of nutritional status between the 2 groups. Endoscopic examination 1 year after gastrectomy showed reflux esophagitis in 26 patients (17 %) in the BI group versus 10 patients (6 %) in the RY group (p = 0.0037), while remnant gastritis was observed in 71 patients (46 %) in the BI group versus 44 patients (28 %) in the RY group (p = 0.0013); differences were significant for both conditions. Multivariable analysis showed that the only reconstruction was the independently associated factor with the incidence of reflux esophagitis.

Conclusions

RY reconstruction was not superior to BI in terms of body weight change or other aspects of nutritional status at 1 year after surgery, although RY more effectively prevented reflux esophagitis and remnant gastritis after distal gastrectomy.