Implementation of an educational program for pancreaticoduodenectomy in a university hospital: a retrospective observational study

Objective::No ideal training system exists for pancreaticoduodenectomy (PD). We developed an educational system that uses an objective structured assessment of ...     

Methylglyoxal Induces Inflammation,Metabolic Modulation and Oxidative Stress in Myoblast Cells

Uremic sarcopenia is a serious clinical problem associated with physical disability and increased morbidity and mortality. Methylglyoxal (MG) is a highly reactive, dicarbonyl uremic toxin that accumulates in the circulatory system in patients with chronic kidney disease (CKD) and is related to the pathology of uremic sarcopenia. The pathophysiology of uremic sarcopenia is multifactorial; however, the details remain unknown. We investigated the mechanisms of MG-induced muscle atrophy using mouse myoblast C2C12 cells, focusing on intracellular metabolism and mitochondrial injury. We found that one of the causative pathological mechanisms of uremic sarcopenia is metabolic flow change to fatty acid synthesis with MG-induced ATP shortage in myoblasts. Evaluation of cell viability revealed that MG showed toxic effects only in myoblast cells, but not in myotube cells. Expression of mRNA or protein analysis revealed that MG induces muscle atrophy, inflammation, fibrosis, and oxidative stress in myoblast cells. Target metabolomics revealed that MG induces metabolic alterations, such as a reduction in tricarboxylic acid cycle metabolites. In addition, MG induces mitochondrial morphological abnormalities in myoblasts. These changes resulted in the reduction of ATP derived from the mitochondria of myoblast cells. Our results indicate that MG is a pathogenic factor in sarcopenia in CKD.     

Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura

Immunoregulatory CD4(+)CD25(+) T cells play an important role in the induction and maintenance of peripheral self-tolerance. These professional regulatory cells prevent the activation and proliferation of potentially autoreactive T cells that have escaped thymic deletion. Therefore, CD4(+)CD25(+) T cells are believed to possibly play an important role in pathogenic autoimmune diseases. We measured the count of CD4(+)CD25(+) T cells in 44 patients with idiopathic thrombocytopenic purpura (ITP), and the number of CD4(+)CD25(+) T cells and clinical features were then analyzed. By using a flow cytometric analysis, the number of CD4(+)CD25(+) T cells in the patients with ITP showed a very wide distribution in comparison to healthy volunteers. The number of CD4(+)CD25(+) T cells was significantly lower in the ITP patients in the severe phase, and in patients positive for anti-glycoprotein IIb-IIIa antibody. However, the number of those cells increased in the patients at the complete remission phase, especially after a splenectomy. The Foxp3 mRNA levels of peripheral blood mononuclear cells (PBMC) of ITP patients were higher with an improved platelet count than in those with a low platelet count. In addition, the Foxp3 mRNA levels closely correlated with the number of CD4(+)CD25(+) cells. These mechanisms remain to be fully elucidated, however, the count of CD4(+)CD25(+) T cells is considered to possibly be related to the severity of ITP.     

The effects of physiological fluctuation of serum potassium levels on excitability properties in healthy human motor axons.

OBJECTIVE: Previous axonal excitability studies suggest hyperkalemia or hypokalemia can significantly alter membrane potential and thereby, excitability properties. We studied whether physiological fluctuation of serum potassium levels affects axonal excitability in normal human axons. METHODS: Threshold tracking was used to measure strength-duration properties, refractory periods, supernormality, and threshold electrotonus in median motor axons of 12 normal volunteers. In each subject, the excitability indices and serum potassium levels were measured three times (baseline, 2h later, and 2 weeks later). RESULTS: The pooled data (n=36) showed significant correlation of the relative refractory period, supernormality, and depolarizing threshold electrotonus with potassium levels. Among each trial (12 subjects) the correlation did not reach statistical significance occasionally. Strength-duration properties, refractoriness, late subnormality, and hyperpolarizing threshold electrotonus were not significantly affected by serum potassium levels. CONCLUSIONS: Even in the normal range, serum potassium levels could slightly alter axonal excitability of human axons. Among excitability indices, the relative refractory period, supernormality, and threshold electrotonus are sensitive to potassium levels. SIGNIFICANCE: Physiological fluctuation of serum potassium levels could partly be responsible for inter- and intra-subject variability of excitability indices.     

JPN Guidelines for the management of acute pancreatitis:surgical management

Acute pancreatitis represents a spectrum of disease ranging from a mild, self-limited course to a rapidly progressive, severe illness. The mortality rate of severe acute pancreatitis exceeds 20%, and some patients diagnosed as mild to moderate acute pancreatitis at the onset of the disease may progress to a severe, life-threatening illness within 2–3 days. The Japanese (JPN) guidelines were designed to provide recommendations regarding the management of acute pancreatitis in patients having a diversity of clinical characteristics. This article sets forth the JPN guidelines for the surgical management of acute pancreatitis, excluding gallstone pancreatitis, by incorporating the latest evidence for the surgical management of severe pancreatitis in the Japanese-language version of the evidence-based Guidelines for the Management of Acute Pancreatitis published in 2003. Ten guidelines are proposed: (1) computed tomography-guided or ultrasound-guided fine-needle aspiration for bacteriology should be performed in patients suspected of having infected pancreatic necrosis; (2) infected pancreatic necrosis accompanied by signs of sepsis is an indication for surgical intervention; (3) patients with sterile pancreatic necrosis should be managed conservatively, and surgical intervention should be performed only in selected cases, such as those with persistent organ complications or severe clinical deterioration despite maximum intensive care; (4) early surgical intervention is not recommended for necrotizing pancreatitis; (5) necrosectomy is recommended as the surgical procedure for infected pancreatic necrosis; (6) simple drainage should be avoided after necrosectomy, and either continuous closed lavage or open drainage should be performed; (7) surgical or percutaneous drainage should be performed for pancreatic abscess; (8) pancreatic abscesses for which clinical findings are not improved by percutaneous drainage should be subjected to surgical drainage immediately; (9) pancreatic pseudocysts that produce symptoms and complications or the diameter of which increases should be drained percutaneously or endoscopically; and (10) pancreatic pseudocysts that do not tend to improve in response to percutaneous drainage or endoscopic drainage should be managed surgically.     

Diagnosis of nail psoriasis: evaluation of nail-derived microRNAs as potential novel biomarkers

Background

MicroRNA levels in sera or hair may potentially be useful biomarkers for various diseases. The diagnosis of nail diseases is sometimes difficult, and nail psoriasis without skin lesions is indistinguishable from nail changes caused by other diseases.

Objectives

We evaluated nail microRNA levels as biomarkers for the diagnosis of psoriasis patients.

Materials & methods

MicroRNA levels were examined in psoriasis patients with (11 patients) and without (six patients) nail changes. Normal control nails were collected from 17 healthy subjects. Eight patients with other diseases who also had nail changes were also included as disease controls.

Results

Microarray, real-time PCR, and in situ hybridisation indicated that the expression levels of nail miR- 4454 were decreased in psoriasis patients with nail changes, compared to those patients with other diseases involving nail change, or healthy subjects. The miR-4454 levels in nails showed a significant inverse correlation with the Nail Psoriasis Severity Index (NAPSI) score, suggesting that nail miR-4454 levels reflect nail condition.

Conclusion

The levels of microRNAs in nails may be suitable biomarkers for diagnosis or evaluation of disease activity of psoriasis.

     

Identification of four novel mutations in F5 associated with congenital factor V deficiency

Coagulation factor V (FV) deficiency is a rare bleeding disorder characterized by low coagulant and antigen levels of FV with bleeding symptoms ranging from mild to severe. Only a limited number of mutations have been reported because of the large size of the factor V gene (F5) as well as the low prevalence. In this study, we have identified four novel mutations in F5 in five unrelated patients with congenital FV deficiency. All the patients, including two with undetectable FV activity, were asymptomatic and were found to have prolonged prothrombin time and activated partial thromboplastin time during preoperative screening or routine examinations. All four mutations found in this study are either missense or in-frame deletion. This is in contrast with previous reports of a high frequency of mutations introducing premature termination codons in inherited FV deficiency. Missense mutations of F5 might produce a mild phenotype and are not frequently diagnosed. Although FV deficiency is a very rare disorder with a predicted incidence of one in 1 million, this study suggests that the numbers of F5 mutations, especially missense mutations, are higher than estimated.     

Novel vaginoplasty technique involving the use of peritoneal flaps during laparoscopic radical hysterectomy for early-stage cervical cancer

Radical hysterectomy is often performed to treat early-stage cervical cancer in women of reproductive age, and sexual dysfunction due to postoperative vaginal shortening is a major concern [^1,2]. Vaginoplasty using various techniques is commonly performed in patients with congenital vaginal agenesis [³]. However, there are few reports of vaginoplasty being performed for vaginal shortening after radical hysterectomy in a patient with cervical cancer [^4,5]. We demonstrate a novel vaginoplasty technique in which peritoneal flaps are used during laparoscopic radical hysterectomy to prevent postoperative vaginal shortening and consequent sexual dysfunction in patients with early-stage cervical cancer. A 37-year-old woman with early-stage cervical cancer who wished to perform sexual activity postoperatively underwent laparoscopic radical hysterectomy and vaginoplasty. After radical hysterectomy, the residual vaginal length was 4 cm. The dissected peritoneum of pouch of Douglas (posterior peritoneal flap) was sutured to the posterior vaginal stump. The supravesical peritoneum was dissected from the ventral to the dorsal side to create an anterior peritoneal flap, which was inverted, pulled down, and sutured to the anterior vaginal stump. The anterior peritoneal flap and suprarectal peritoneum were sutured to create a 10-cm neovaginal vault. Subsequently, a methacrylic resin mold was inserted into the neovagina to prevent postoperative neovaginal stenosis. The patient had sexual intercourse 3 months postoperatively. She was satisfied with the sexual activity and experienced no vaginal shortening or stenosis. Our novel vaginoplasty technique is feasible and effective for preventing sexual dysfunction by lengthening the vagina during laparoscopic radical hysterectomy for early-stage cervical cancer.Trial RegistrationJapan Registry of Clinical Trials Identifier: jRCT1030210227