Risk of herpes zoster in the Japanese population with immunocompromising and chronic disease conditions: Results from a claims database cohort study,from 2005 to 2014

Older adults, women and patients with immunocompromised (IC) or chronic medical conditions have a higher incidence of herpes zoster (HZ) and are at higher risk of developing HZ-associated complications such as postherpetic neuralgia. The incidence rates of HZ in various IC and chronic conditions have been previously reported in a retrospective cohort study using claims data from Japanese adults. Here, we report further analyses from this cohort using univariate and multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) associated with different IC and chronic conditions. After adjusting for multiple covariates (age, sex and other coexisting medical conditions), the risk of HZ was higher in women (HR, 1.14 [95% CI, 1.11–1.17]), irrespective of age and increased with increasing age, being substantially higher in patients aged 65 years or older (HR, 3.28 [95% CI, 3.07–3.49]) when compared with those aged 18–29 years. The highest HRs were observed for the following specific IC conditions; hematopoietic stem cell transplant recipients (HR, 9.85 [95% CI, 6.80–14.28]), hematological malignancy (HR, 3.22 [95% CI, 2.54–4.09]), systemic lupus erythematosus (HR, 2.46 [95% CI, 1.45–4.15]) and inflammatory bowel disease (HR, 1.59 [95% CI, 1.14–2.21]). For most other IC and chronic medical conditions, a higher risk was also apparent though of a smaller magnitude (HRs ranging from 1.2 to <1.5). These results corroborate our previous findings and demonstrate an increased risk of HZ associated with different IC and chronic conditions.     

Successful Resection of Hepatocellular Carcinoma with Bronchobiliary Fistula Caused by Repeated Transcatheter Arterial Embolizations: Report of a Case

Bronchobiliary fistula (BBF) is a rare but life-threatening condition. We herein describe a rescued case of a patient with hepatocellular carcinoma (HCC) who developed BBF as a late complication of transcatheter arterial embolization (TAE). A 66-year-old man underwent repeated TAE for a large HCC during a 3-year period. Massive biliptysis developed after the last treatment and bronchoscopy proved the presence of BBF. Radiological studies exhibited a necrotic HCC in the right liver with a tumor thrombus protruding into the common bile duct. Localized pneumonia was also present in the right lung. A right hemihepatectomy with a bile duct tumor thrombectomy and a right lower lobectomy of the lung were performed. He is presently doing well at 6 months after surgery. Increased intraluminal pressure of the biliary system due to obstruction by the tumor thrombus is considered to have led to the rupture of the liver abscess into the bronchus, thus creating a BBF. This is the first successfully resected case of HCC associated with BBF.     

A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells,Muse Cells,Directly Commit to the Replacement of Liver Components

Genotyping graft livers by short tandem repeats after human living‐donor liver transplantation (n = 20) revealed the presence of recipient or chimeric genotype cases in hepatocytes (6 of 17, 35.3%), sinusoidal cells (18 of 18, 100%), cholangiocytes (15 of 17, 88.2%) and cells in the periportal areas (7 of 8, 87.5%), suggesting extrahepatic cell involvement in liver regeneration. Regarding extrahepatic origin, bone marrow mesenchymal stem cells (BM‐MSCs) have been suggested to contribute to liver regeneration but compose a heterogeneous population. We focused on a more specific subpopulation (1–2% of BM‐MSCs), called multilineage‐differentiating stress‐enduring (Muse) cells, for their ability to differentiate into liver‐lineage cells and repair tissue. We generated a physical partial hepatectomy model in immunodeficient mice and injected green fluorescent protein (GFP)‐labeled human BM‐MSC Muse cells intravenously (n = 20). Immunohistochemistry, fluorescence in situ hybridization and species‐specific polymerase chain reaction revealed that they integrated into regenerating areas and expressed liver progenitor markers during the early phase and then differentiated spontaneously into major liver components, including hepatocytes (≈74.3% of GFP‐positive integrated Muse cells), cholangiocytes (≈17.7%), sinusoidal endothelial cells (≈2.0%), and Kupffer cells (≈6.0%). In contrast, the remaining cells in the BM‐MSCs were not detected in the liver for up to 4 weeks. These results suggest that Muse cells are the predominant population of BM‐MSCs that are capable of replacing major liver components during liver regeneration.     

Increased Akt and phosphorylated Akt expression are associated with malignant biological features of prostate cancer in Japanese men

OBJECTIVE: To investigate the relationship between the expression of Akt (a serine/threonine kinase that plays a central role in tumorigenesis), phosphorylated Akt (p-Akt), prostate cancer tumour grade, androgen receptor (AR)-staining score, and Ki67 labelling index (LI) in Japanese men. PATIENTS, MATERIALS AND METHODS: The expression and activation of the cell survival protein Akt was analysed by immunohistochemical staining of paraffin-embedded tissue microarray sections of prostate carcinoma taken from 52 Japanese men who under radical prostatectomy. The correlation between the expression of Akt and p-Akt, and their relationship to primary Gleason grade, AR expression and Ki-67 LI was investigated. RESULTS: The expression of Akt and p-Akt were positively related to primary Gleason grade (Fisher's exact test, P = 0.002 and P = 0.032, respectively). Both AR-staining score and Ki67 LI were were positively related to the expression of Akt (both P < 0.001) and p-Akt (P < 0.001 and P = 0.008, respectively). There was a significant positive correlation between the expression of Akt and p-Akt (Spearman's correlation, r = 0.644, P < 0.001). CONCLUSIONS: Increased expression of both Akt and p-Akt were associated with higher tumour grade as well as a higher AR-staining score and Ki67 LI. These data indicate that Akt and p-Akt might be molecular markers for detecting malignant biological features of prostate cancer in the Japanese population.     

Significance of Extensive Surgery Including Resection of the Pancreas Head for the Treatment of Gallbladder Cancer—From the Perspective of Mode of Lymph Node Involvement and Surgical Outcome

The present study aimed to clarify the efficacy of extensive surgery, including pancreas head resection, for more complete lymphadenectomy in the treatment of gallbladder carcinoma. The study involved retrospective analyses of 65 consecutive patients with gallbladder carcinoma who underwent surgical resection between 1982 and 2003. Of these 65 patients, 41.5% displayed node-positive disease and among them 23.1% had positive para-aortic nodes. Of six node-positive 5-year survivors, five underwent pancreatoduodenectomy combined with S4aS5 hepatic subsegmentectomy. The 5-year survival rates were 76.2% for pN0, 30.0% for pN1, 45.8% for pN2, and 0% for pM1[lymph], respectively. Significant differences existed in survival rates. Postoperative recurrence was observed in 24.1% (13/54) of patients who underwent R0 resection. Of the four patients who displayed lymph node recurrence, two had pericholedocal and/or posterior pancreatoduodenal lymph node metastasis at the time of surgery and underwent pancreas-preserving regional lymphadenectomy. These results suggest that extensive resection, including resection of the pancreatic head, is effective in selected patients with up to pN2 lymph node metastasis, as long as complete removal of the cancer can be achieved. Pancreatoduodenectomy combined with S4aS5 hepatic subsegmentectomy should be considered when lymph node metastasis is obvious and the patient is in good condition.     

Neutrophil gelatinase-associated lipocalin is a sensitive biomarker for the early diagnosis of acute rejection after living-donor kidney transplantation

Background

Early diagnosis of kidney allograft dysfunction is crucial for the management and long-term survival of transplanted kidneys. We investigated whether neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) are capable of being used as novel biomarkers of acute kidney allograft dysfunction.

Methods

We measured serum and urine NGAL, urine IL-18, and urine L-FABP levels on the first 3 days after transplantation. To assess the diagnostic sensitivity of these biomarkers, a receiver-operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to quantify the accuracy of the parameter. Sections from paraffin-embedded biopsy specimens were examined by immunohistochemistry for NGAL expression.

Results

Twelve cases were clinically diagnosed as acute rejection (AR) by renal biopsy. Urine NGAL was the most sensitive of these markers for detection of acute kidney allograft dysfunction. The cutoff value of urine NGAL was 66.0 ng/ml, with an AUC of 0.79 (95 % CI 0.68–0.88). Sensitivity of serum NGAL was about the same as urine NGAL with an AUC of 0.75 (0.64–0.85). IL-18 and L-FABP were 0.584 (95 % CI 0.433–0.725) and 0.612 (95 % CI 0.460–0.749), respectively. NGAL was more useful than other biomarkers to detect AR of kidney allograft dysfunction. NGAL staining intensity was significantly increased in the proximal tubules of the transplants with AR than in transplants that were not acutely rejected.

Conclusion

Urine NGAL level was found to be the most sensitive biomarker of acute kidney allograft dysfunction after living-donor kidney transplantation.     

Development of plasticity of brain function with repeated trainings and passage of time after basal forebrain lesions in rats

Summary Basal forebrain (BF) lesion-induced amnesia in rats is widely used as an animal model of Alzheimer's disease (AD). To study the plasticity of brain function in BF-lesioned rats, we examined the effects of repeated trainings and the passage of time after the lesion on learning ability 3 weeks and 3 months after BF-lesions with ibotenic acid, using an eight-arm radial maze and passive avoidance tasks, and measured choline acetyltransferase (ChAT) activity. Both time and re-training played important roles in the recovery of the ability to learn, as measured with the eight-arm radial maze task, but not the passive avoidance task. In contrast, ChAT activity in the frontal cortex, which was low 3 weeks after the lesion, still low 3 months after lesion, even though the ability to learn had recovered. Recovery of the ability to learn can be attributed to undamaged cholinergic neurons, or to other neuronal systems, or to both. This animal model can be used to demonstrate the plasticity of brain function.     

A Quantitative Model of Sporadic Axonal Degeneration in the Drosophila Visual System

In human neurodegenerative diseases, neurons undergo axonal degeneration months to years before they die. Here, we developed a system modeling early degenerative events in Drosophila adult photoreceptor cells. Thanks to the stereotypy of their axonal projections, this system delivers quantitative data on sporadic and progressive axonal degeneration of photoreceptor cells. Using this method, we show that exposure of adult female flies to a constant light stimulation for several days overcomes the intrinsic resilience of R7 photoreceptors and leads to progressive axonal degeneration. This was not associated with apoptosis. We furthermore provide evidence that loss of synaptic integrity between R7 and a postsynaptic partner preceded axonal degeneration, thus recapitulating features of human neurodegenerative diseases. Finally, our experiments uncovered a role of postsynaptic partners of R7 to initiate degeneration, suggesting that postsynaptic cells signal back to the photoreceptor to maintain axonal structure. This model can be used to dissect cellular and circuit mechanisms involved in the early events of axonal degeneration, allowing for a better understanding of how neurons cope with stress and lose their resilience capacities.SIGNIFICANCE STATEMENT Neurons can be active and functional for several years. In the course of aging and in disease conditions leading to neurodegeneration, subsets of neurons lose their resilience and start dying. What initiates this turning point at the cellular level is not clear. Here, we developed a model allowing to systematically describe this phase. The loss of synapses and axons represents an early and functionally relevant event toward degeneration. Using the ordered distribution of Drosophila photoreceptor axon terminals, we assembled a system to study sporadic initiation of axon loss and delineated a role for non-cell-autonomous activity regulation in the initiation of axon degeneration. This work will help shed light on key steps in the etiology of nonfamilial cases of neurodegenerative diseases.