Disruption of leptin receptor expression in the pancreas directly affects beta cell growth and function in mice

Obesity is characterized by hyperinsulinemia, hyperleptinemia, and an increase in islet volume. While the mechanisms that hasten the onset of diabetes in obese individuals are not known, it is possible that the adipose-derived hormone leptin plays a role. In addition to its central actions, leptin exerts biological effects by acting in peripheral tissues including the endocrine pancreas. To explore the impact of disrupting leptin signaling in the pancreas on beta cell growth and/or function, we created pancreas-specific leptin receptor (ObR) KOs using mice expressing Cre recombinase under the control of the pancreatic and duodenal homeobox 1 (Pdx1) promoter. The KOs exhibited improved glucose tolerance due to enhanced early-phase insulin secretion, and a greater beta cell mass secondary to increased beta cell size and enhanced expression and phosphorylation of p70S6K. Similar effects on p70S6K were observed in MIN6 beta cells with knockdown of the ObR gene, suggesting crosstalk between leptin and insulin signaling pathways. Surprisingly, challenging the KOs with a high-fat diet led to attenuated acute insulin secretory response to glucose, poor compensatory islet growth, and glucose intolerance. Together, these data provide direct genetic evidence, from a unique mouse model lacking ObRs only in the pancreas, for a critical role for leptin signaling in islet biology and suggest that altered leptin action in islets is one factor that contributes to obesity-associated diabetes.     

Pipeline flow diversion with adjunctive coil embolization for internal carotid artery aneurysms following an intradural component: results in 46 consecutive aneurysms from a Japanese single-center experience

In the treatment of an intracranial aneurysm with the flow diverter, the combined use of coil embolization can help promote subsequent progressive thrombosis within the aneurysm sac and reduce the risk of delayed aneurysm rupture. This study retrospectively reviewed outcomes of patients who had undergone the Pipeline Embolization Device (PED) with adjunctive coil embolization (PED/coil) at a single center to determine its safety and efficiency. Patients with internal carotid artery aneurysms following an intradural component were selected for PED/coil between 2015 and 2020. All patients were premedicated with dual antiplatelet therapy of aspirin plus clopidogrel or prasugrel. A minimal number of PEDs were deployed, with coils inserted using a stent-jail technique, avoiding dense packing. A total of 46 aneurysms (43 patients; median dome size, 11.6 mm; median neck width, 6.3 mm) were treated with PED/coil. The median volume embolization ratio was 14.8%. The degree of angiographic filling at the 6-month and latest angiography showed complete occlusion in 60.5% (26/43) and 70.5% (31/44), respectively. Small (<?10 mm) aneurysms achieved a higher complete occlusion rate in the early period; a lower cumulative incidence of aneurysm occlusion was observed in large and giant (≥?10 mm) aneurysms (P?=?.024). The median clinical follow-up was 22 months, and no aneurysm ruptures occurred. Favorable clinical outcomes were achieved, with permanent neurological morbidity of 4.7% and no mortality. PED/coil demonstrated a high angiographic occlusion rate at an early stage. Loosely packed coils are sufficient to obliterate aneurysms effectively.

     

Pseudoaneurysm of the superficial femoral artery after retrograde intramedullary nailing for a supracondylar femoral fracture

Vascular complications of distal femoral fractures are rare but can have disastrous consequences if not recognised and treated promptly. We present the case of a 55-year-old woman who developed a pseudoaneurysm of the superficial femoral artery after osteosynthesis to repair a supracondylar femoral fracture. Eight weeks after surgery, swelling of the right thigh persisted and was accompanied by severe pain. Enhanced computed tomography revealed a pseudoaneurysm in the medial aspect of the affected thigh. Open surgical repair was performed by direct arterial suture. Although the true aetiology of the development of the pseudoaneurysm is unknown, a bony fragment from the reduction manoeuvre may have damaged the adventitia of the superficial femoral artery. In cases of continuous thigh swelling after osteosynthesis to repair a supracondylar femoral fracture, a diagnosis of pseudoaneurysm should be considered and treatment should be initiated immediately.     

Technical tips for intersphincteric resection: how to take out the rectum

Intersphincteric resection (ISR) is an ideal technique that preserves the anus, regardless of whether the internal anal sphincter is removed. However, it is difficult to dissect the anterior wall of the rectum from the adjacent organs. We herein describe a safe and useful ISR technique which draws out the rectum through the anus. The intersphincteric space (ISS) between the internal and external anal sphincter muscles was first transabdominally dissected. Next, the transanal dissection was advanced into the ISS bilaterally from the posterior side without dissecting the anterior wall of the anal canal, and the sigmoid colon and rectum were drawn out through the anus. Dissection between the anterior wall of the rectum and prostate/vagina could be easily performed under direct vision. This technique enables the dissection without any risk of a positive surgical margin or unexpected bleeding, and avoids injury to adjacent organs. This technique seems to be a safe and useful dissection technique for approaching the anterior wall of the anal canal.     

Single-centre retrospective observational study comparing trough blood concentration and safety of teicoplanin formulations

Teicoplanin formulations are marketed as antibiotic mixtures with several compounds that share the same core structure. Recent studies conducted in vitro have reported differences in the composition ratio of different teicoplanin products. In this retrospective study, we examined the trough blood concentration of the originator brand and a generic teicoplanin product. Target patients were retrospectively assigned to the originator (Targocid) or generic group. The groups were matched 1:1 using propensity scores. The initial trough blood concentration analysis identified 44 matches. In both groups, the median dosing day for the first measurements was 4, respectively. The initial trough blood concentration of the originator group was significantly higher (mean ± SD, 16.3 ± 4.5 mg/L) than that of the generic group (12.8 ± 4.7 mg/L; 95% CI, ?5.4 to ?1.6). A significant difference was observed in the frequency of serum creatinine elevation in the study of the frequency of adverse events using Common Terminology Criteria for Adverse Events (originator group, 41.9% vs generic group, 20.9%). In cases where discontinuation was necessary due to side effects, there were three patients in the originator group and one patient in the generic group. This study found that trough blood concentration differed between formulations. Therefore, correction might be necessary while monitoring drug concentration in the blood. Trough blood concentrations are used as surrogate markers for efficacy and safety, so further studies on differences in efficacy and safety between formulations are required.     

Perioperative changes in plasma antithrombin activity and platelet counts in patients undergoing gynecologic surgery

The relationships among perioperative changes in plasma antithrombin (AT) activity, platelet counts, and clinical risk factors for postoperative thromboembolism has not been studied extensively in gynecologic patients. AT activity and platelet counts were determined preoperatively and on postoperative days 1 and 7 in 74 patients who underwent gynecologic surgery. The relationships between each clinical risk factor for postoperative thromboembolism and the decrease in AT activity and platelet count were analyzed using a univariate logistic regression model. No clinically significant thromboembolism occurred in any patient. AT activity and platelet counts decreased significantly on postoperative day 1 and exceeded preoperative levels on day 7. Postoperative patients with malignancy were more likely to exhibit decreased AT activity. AT activity decreased significantly with increases in operating time and blood loss. Known risk factors for postoperative thromboembolism did not appear to be associated with postoperative decreases in platelet counts. Transient hyperconsumption of AT and platelets occurs immediately after gynecologic surgery. Surgery-induced AT deficiency may contribute to postoperative thromboembolism in patients with long operating times and significant blood loss.     

A case of pleomorphic carcinoma of the pancreas showing sequential histological change by immunohistochemical study

Summary Pleomorphic carcinoma of the pancreas is a rare, histologically characterized pancreatic tumor with a rapid and fatal course. We report a case of a resected pleomorphic carcinoma located in the body of the pancreas in a 61-yr-old male. Histological analysis of the resected specimen revealed the coexistence of pleomorphic carcinoma with adenocarcinoma, but the recurrent tumors at autopsy 20 mo later were only of the adenocarcinomatous type. Cells in the adenocarcinomatous component showed a diffuse reactivity for CA19-9, CEA, and cytokeratin, and a focal reactivity for vimentin. In contrast, vimentin was diffusely expressed in pleomorphic lesion. Adenocarcinoma at autopsy expressed CA19-9, CEA, and cytokeratin, but not vimentin. These findings suggest that the recurrent adenocarcinoma may have developed as a consequence of sequential change in the nature of the tumor.     

Serum levels of cytokines in patients with colorectal cancer: Possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis

Serum levels of interleukin-1 (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured preoperatively in 24 patients with colorectal cancer. IL-1β was not elevated, IL-6 and IL-8 were markedly elevated, and GM-CSF was slightly elevated. TNF-α was not detected in most patients. Serum IL-6 levels correlated closely with serum IL-8 levels and with serum carbohydrate antigen (CA) 19-9 levels. Serum IL-6 levels were significantly higher in patients whose tumors exceeding 5.0 cm in diameter or spreading circumferentially. Serum IL-8 levels showed significant differences according to histological type, being lower in well differentiated adenocarcinoma compared to other types. Serum levels of IL-6 and IL-8 were significantly higher in patients with liver metastasis than in those without liver metastasis and serum levels of both these cytokines were also significantly higher in patients with lung metastasis than in those without lung metastasis. These results suggest that IL-6 and IL-8 may play an important role in the hematogenous metastasis of colorectal cancer.