Efficacy of adipose tissue-derived mesenchymal stem cells for fulminant hepatitis in mice induced by concanavalin A

Background and Aim: Fulminant hepatitis is mainly caused by excessive immune response‐mediated liver injury and its definitive therapy is liver transplantation. Mesenchymal stem cells, one of the adult stem cells, have an immunomodulatory effect on immune cells and reside in various tissues. The aim of this study was to investigate a therapeutic effect of adipose tissue‐derived mesenchymal stem cells (ASCs) on fulminant hepatitis induced by concanavalin A (ConA). Methods: The ASCs were isolated from adipose tissues of BALB/c mice and confirmed by detection of cell surface markers and induction of multi‐lineage differentiation. BALB/c mice were injected with ConA and treated with ASCs, phosphate buffered saline (PBS) or splenocytes (SPLCs). Survival rates, levels of serum liver enzymes, titers of serum cytokines, histopathology and localization of ASCs were investigated. Result: The survival rate of ASC‐injected mice significantly increased compared to PBS or SPLC‐injected mice. This effect was dependent on doses and timing of ASCs injected. Improvement of liver enzyme levels, histopathological changes and suppression of inflammatory cytokine production were observed in ASC‐injected mice. Fluorescent stained ASCs were detected in inflammatory liver, but not in normal liver. Conclusion: These results suggest that ASC treatment has a high potential to be an innovative therapy for fulminant hepatitis.     

Weight-based high- and low-dose ribavirin in combination with peginterferon α-2b therapy for genotype 2 chronic hepatitis C: A randomized trial

Aim: The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. Methods: We compared the efficacy and tolerability of the 24‐week peginterferon α‐2b (1.5 µg/kg/week) therapy in combination with a weight‐based higher dose (600–1000 mg) and lower dose (400–800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. Results: A total of 120 patients were randomized to a higher‐dose or a lower‐dose group. Sustained virological response (SVR) by intention‐to‐treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6–89.5) patients in the higher‐dose group and 41/60 (68.3%, 90% CI: 58.5–78.2) patients in the lower‐dose group (difference, ?12.7%; 90% CI, ?25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher‐dose and the lower‐dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs <9.5 mg/kg per day; odds ratio = 3.34; 95% CI, 1.41–7.92; P = 0.006). Twenty‐one (36.2%) in the higher‐dose group required ribavirin dose reduction because of anemia, whereas seven patients (11.7%) did in the lower‐dose group (P < 0.01). Three of the higher‐dose group and two of the lower‐dose group required premature termination of therapy. Conclusions: Weight‐based lower‐dose ribavirin regimen was not equivalent to the higher‐dose counterpart in the treatment of HCV genotype 2. We discourage treating these patients with low‐dose ribavirin regimens. The peginterferon therapy in combination with ribavirin at a weight‐based higher dose (600–1000 mg) remains the standard‐of‐care treatment for this genotype.     

Can decompression surgery relieve low back pain in patients with lumbar spinal stenosis combined with degenerative lumbar scoliosis?

Introduction

Decompression with fusion is usually recommended in patients with lumbar spinal stenosis (LSS) combined with degenerative lumbar scoliosis (DLS). However, elderly patients with LSS and DLS often have other comorbidities, and surgical treatment must be both safe and effective. The aim of this study was to investigate whether decompression surgery alone alleviates low back pain (LBP) in patients with LSS and DLS, and to identify the predictors of postoperative residual LBP.

Materials and methods

A total of 75 patients (33 males and 42 females) with a mean age of 71.8 years (range 53–86 years) who underwent decompression surgery for LSS with DLS (Cobb angle ≥ 10°) and had a minimum follow-up period of 1 year, were retrospectively reviewed using the Japanese Orthopaedic Association scoring system for the assessment of lumbar spinal diseases (JOA score). Radiographic measurements included coronal and sagittal Cobb angles, apical vertebral rotation (Nash-Moe method), and anteroposterior and lateral spondylolisthesis. Logistic regression analysis was performed to investigate the predictors of residual LBP after surgery.

Results

Forty-nine patients had preoperative LBP, of which 29 (59.1 %) experienced postoperative relief of LBP. Logistic regression analysis demonstrated that the degree of apical vertebral rotation on preoperative radiography was significantly associated with postoperative residual LBP (odds ratio, 8.16, 95 % confidence interval, 1.55–83.81, p = 0.011).

Conclusion

A higher degree of apical vertebral rotation may therefore be an indicator of mechanical LBP in patients with LSS and DLS. Decompression with fusion should be recommended in these patients.     

Subchondral cysts in dysplastic osteoarthritic hips communicate with the joint space: analysis using three-dimensional computed tomography

Introduction

Bone cyst formation in hips increases as osteoarthritis worsens. Although bone cysts in hips have been described in many studies, their etiology remains unclear and under debate. The purpose of this study was to investigate the communication between a bone cyst and the joint space, as well as the relationship between the severity of osteoarthritis and the formation of subchondral bone cysts in dysplastic hips.

Method

We studied bone cysts from 150 dysplastic hips in 97 patients by computed tomography (CT) and plain radiography. We investigated the distribution of the bone cysts and the presence or absence of a communication path between the cysts and the joint space by three-dimensional (3D) CT.

Result

Of the 150 hips, 94 acetabula and 55 femoral heads were found to contain cysts. Of the 94 hips containing acetabular cysts, 89 and 5 hips showed black lines and gray lines connecting the cyst and the joint space, respectively, on 3D-CT. The rate of cyst presentation in the hip increased as the joint space became narrower. The number of hips that possessed cysts in the anterior and/or middle portion was significantly higher than that in the posterior portions.

Conclusion

Bone cysts in dysplastic osteoarthritic hips were found to communicate with the joint space in all cases. This suggests that the formation and enlargement of the cysts in dysplastic hips may be greatly influenced by the joint fluid. Cyst formation was initially observed in the anterior acetabulum, gradually progressing to involve the entire joint, including the posterior acetabulum and the femoral head, with worsening of the osteoarthritis.     

Incidence of steroid-associated osteonecrosis of the talus: a prospective MRI study

Objective

The purpose of this study was to determine the incidence of steroid-associated osteonecrosis (ON) of the talus in systemic lupus erythematosus (SLE) patients using a prospective magnetic resonance imaging (MRI) study.

Methods

We prospectively evaluated 110 SLE patients (220 tali) who required corticosteroid therapy using MRI. The incidence of ON of the talus was compared with the incidence of ON of the femoral head. We also divided these patients into two groups: those with and without ON of the talus. We compared these groups for gender differences, ages at initial corticosteroid therapy, and highest daily corticosteroid dosages.

Results

The incidence of ON of the talus was significantly lower than the incidence of ON of the femoral head (7.3 versus 49.5 %; p?<?0.001). No significant differences for gender, age at initial corticosteroid therapy, or highest daily corticosteroid dosage were observed between patients with and without ON of the talus. The rate of ON of the bilateral femoral head was significantly higher in those with ON of the talus than in those without ON of the talus.

Conclusion

Our results revealed that the incidence of ON of the talus was significantly lower than the incidence of ON of the femoral head.     

Serum soluble CD163 levels in patients with influenza-associated encephalopathy

Background: Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin–haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients. Methods: We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects. Results: Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases. Conclusions: Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE.     

Location Frequency of Missed Parathyroid Glands After Parathyroidectomy in Patients with Persistent or Recurrent Secondary Hyperparathyroidism

Background

Reoperative parathyroidectomy (RPTX) because parathyroid glands have been missed is frequently required in patients with secondary hyperparathyroidism (SHPT). The usual locations of these missed glands in patients with SHPT are yet to be fully elucidated.

Methods

We retrospectively investigated the locations of missed glands in 165 patients who underwent RPTX for persistent or recurrent SHPT at our institution from August 1982 to July 2014. At our institution, total parathyroidectomy with forearm autograft is the routine operative procedure for SHPT. We also routinely resect the thymic tongue.

Results

Of 165 patients, 82 underwent initial parathyroidectomy at our institution (Group A), and the remaining 83 underwent initial parathyroidectomy at other institutions (Group B). A total of 239 parathyroid glands were resected (Group A, 93; Group B, 146). Missed glands were most commonly located in the mediastinum (Group A, 22/93) and the thymic tongue (Group B, 31/146).

Conclusions

In patients with persistent or recurrent SHPT, ectopic parathyroid glands are frequently located in the mediastinum and thymic tongue. Therefore, resecting the thymic tongue during the initial operation may reduce the need for RPTX.

     

Characteristics of Persistent Hyperparathyroidism After Renal Transplantation

Background

Persistent hyperparathyroidism (HPT) after renal transplantation (RTx), termed tertiary HPT (THPT), is not uncommon. However, risk factors and appropriate operative procedures for THPT are poorly understood.

Methods

A retrospective study of patients who underwent RTx without pre-transplant parathyroidectomy (PTx) was performed at our hospital between January 2001 and March 2011. Risk factors for the development of THPT were investigated by comparing THPT and non-THPT groups. We retrospectively analyzed patients with THPT who underwent total PTx with forearm autograft. Pre- and postoperative (1 year after PTx) laboratory results were analyzed for PTx efficacy.

Results

Data for 520 patients were analyzed. On multivariate analysis, long dialysis duration (p = 0.009, hazard ratio (HR) 1.01), large maximum parathyroid gland size before RTx (p = 0.003, HR 1.23), pre-RTx high intact parathyroid hormone (iPTH) (p = 0.041, HR 1.01), post-RTx (<2 weeks) high calcium (Ca) (p < 0.001, HR 25.04), and post-RTx high alkaline phosphatase (ALP) (p = 0.027, HR 0.99) were identified as risk factors for THPT. Patients who underwent PTx showed significant improvement compared with baseline for serum Ca, phosphorus, iPTH, and ALP. Serum creatinine showed no significant difference.

Conclusions

Several risk factors for THPT development were identified. PTx for patients with THPT significantly improved serum Ca, iPTH, ALP, and phosphorous levels. There was no significant difference in renal function after PTx. Therefore, total PTx with forearm autograft may be an appropriate surgical approach for patients with THPT.

     

Impact of immunohistological subtypes on the long-term prognosis of patients with metastatic breast cancer

Purpose

Although improved long-term prognoses for patients with metastatic breast cancer (MBC) have been demonstrated, few reports address overall survival (OS) with sufficient follow-up. Furthermore, the relevance of immunohistological subtypes to OS in MBC has not been clarified.

Methods

We evaluated, retrospectively, the OS of patients who had been initiated on systemic therapy for MBC between 2000 and 2008.

Results

The subjects of this study were 527 patients with MBC treated by systemic therapy. The median survival time (MST) was 55.5 months. The MST for each immunohistological subtype was as follows: luminal, 59.9 months; luminal-HER2, not reached; triple-negative, 18.6 months; and HER2-enriched, 49.9 months. According to multivariate analysis, metastasis-free intervals of ≥2 years and treatment with anthracycline for MBC were predictive of better OS. The predictors of shorter OS included disease progression after first-line treatment for MBC, triple-negative, and all histological factors, except papillotubular carcinoma, with liver metastasis, and having three or more initial metastatic sites.

Conclusions

The prognosis of the patients with MBC in this series was better than that reported before 2000, which is probably attributable to the use of novel, improved pharmacological agents. For example, luminal-HER2 tumors can be treated using both aromatase inhibitors and trastuzumab. Because of the lower toxicities, it is now possible to administer these agents for longer periods, resulting in better prognoses.