The Oral Minimal Model Method

The simultaneous assessment of insulin action, secretion, and hepatic extraction is key to understanding postprandial glucose metabolism in nondiabetic and diabetic humans. We review the oral minimal method (i.e., models that allow the estimation of insulin sensitivity, β-cell responsivity, and hepatic insulin extraction from a mixed-meal or an oral glucose tolerance test). Both of these oral tests are more physiologic and simpler to administer than those based on an intravenous test (e.g., a glucose clamp or an intravenous glucose tolerance test). The focus of this review is on indices provided by physiological-based models and their validation against the glucose clamp technique. We discuss first the oral minimal model method rationale, data, and protocols. Then we present the three minimal models and the indices they provide. The disposition index paradigm, a widely used β-cell function metric, is revisited in the context of individual versus population modeling. Adding a glucose tracer to the oral dose significantly enhances the assessment of insulin action by segregating insulin sensitivity into its glucose disposal and hepatic components. The oral minimal model method, by quantitatively portraying the complex relationships between the major players of glucose metabolism, is able to provide novel insights regarding the regulation of postprandial metabolism.     

Contribution of Endogenous Glucagon-Like Peptide 1 to Glucose Metabolism After Roux-en-Y Gastric Bypass

The contribution of elevated glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism after Roux-en-Y gastric bypass (RYGB) has been the subject of uncertainty. We used exendin-9,39, a competitive antagonist of GLP-1, to examine glucose metabolism, islet hormone secretion, and gastrointestinal transit in subjects after RYGB and in matched control subjects. Subjects were studied in the presence or absence of exendin-9,39 infused at 300 pmol/kg/min. Exendin-9,39 resulted in an increase in integrated postprandial glucose concentrations post-RYGB (3.6 ± 0.5 vs. 2.0 ± 0.4 mol/6 h, P = 0.001). Exendin-9,39 decreased insulin concentrations (12.3 ± 2.2 vs. 18.1 ± 3.1 nmol/6 h, P = 0.002) and the β-cell response to glucose (ϕ_Total, 13 ± 1 vs. 11 ± 1 × 10⁻⁹ min⁻¹_, P = 0.01) but did not alter the disposition index (DI). In control subjects, exendin-9,39 also increased glucose (2.2 ± 0.4 vs. 1.7 ± 0.3 mol/6 h, P = 0.03) without accompanying changes in insulin concentrations, resulting in an impaired DI. Post-RYGB, acceleration of stomach emptying during the first 30 min by exendin-9,39 did not alter meal appearance, and similarly, suppression of glucose production and stimulation of glucose disappearance were unaltered in RYGB subjects. These data indicate that endogenous GLP-1 has effects on glucose metabolism and on gastrointestinal motility years after RYGB. However, it remains uncertain whether this explains all of the changes after RYGB.     

Using Protamine Can Significantly Reduce the Incidence of Bleeding Complications after Carotid Endarterectomy without Increasing the Risk of Ischemic Cerebral Events

Background

Controversy persists regarding the use of protamine sulfate (PS) during carotid endarterectomy (CEA), chiefly because of conflicting experiences reporting both less bleeding and a higher stroke risk. The goal of the present study was to test the hypothesis that reversing heparin with PS after CEA significantly reduces the incidence of bleeding complications without increasing the risk of postoperative stroke.

Methods

From January 2010 to December 2012 all consecutive patients undergoing CEA under general anesthesia at our institution received 5,000 U of heparin prior to carotid clamping, which was partially (half-dose) reversed with PS 25 mg immediately after declamping (group I). Heparinization had never been reversed with PS in earlier CEAs performed from 1998 to 2009 at the same institution (group II). All patients were assessed preoperatively and postoperatively by a neurologist, and cerebral magnetic resonance imaging was performed in all group I patients to exclude any silent cerebral infarction. End points of the study were bleeding complications, perioperative (30-day) stroke, and death.

Results

Overall, 219 CEAs (201 patients) were performed in group I, and 1,458 CEAs (1,294 patients) in group II. Demographics, risk factors, and preoperative antiplatelet medication were comparable in the two groups. The incidence of adverse events (group I vs group II) was as follows: stroke (0 vs 0.5 % [8/1,458], p = 0.27); death (0 vs 0 %); neck bleeding (0 vs 8.2 % [120/1,458], p < 0.001).

Conclusions

The results of the present study demonstrate that (1) partially neutralizing heparin with PS after CEA can significantly reduce the risk of bleeding complications, and (2) there is no association between the administration of PS and the incidence of postoperative stroke.     

Diagnosis and management of postoperative pancreatic fistula

Background

Postoperative pancreatic fistula (POPF) is the leading complication after partial pancreatic resection and is associated with increased length of hospital stay and resource utilization. The introduction of a common definition in 2005 by the International Study Group of Pancreatic Surgery (ISGPS), which has been since employed in the vast majority of reports, has allowed a reliable comparison of surgical results. Despite the systematic investigation of risk factors and of surgical techniques, the incidence of POPF did not change in recent years, whereas the associated mortality has decreased.

Purpose

The purposes of this review article were to summarize the current evidence on the diagnosis and management strategies of POPF and to provide a concise reference for the practicing surgeons and physicians.

Conclusion

The high incidence of POPF was accompanied by a shift from operative to non-operative management. However, the current management strategy is driven by the patient’s condition and local expertise and is generally based on poor evidence. A randomized trial showed that enteral nutrition is superior to total parenteral nutrition, and pooled data of randomized trials failed to show any advantage of somatostatin analogs for accelerating fistula closure. The choice of percutaneous versus endoscopic drainage of peripancreatic collections remains arbitrary, and—when re-operation is needed—there are very few comparative data regarding local drainage with or without main pancreatic stenting as opposed to anastomotic revision or salvage re-anastomosis. The continuous development of specialist, high-volume units with appropriate resources and multidisciplinary experience in complication management might further improve the evidence and the outcomes.     

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw.     

Peri-implant bone tissues around retrieved human implants after time periods longer than 5 years: a retrospective histologic and histomorphometric evaluation of 8 cases

Only rarely, it is possible to find in the literature histological reports of human retrieved implants, especially after several years of functional loading. These implants can help us in understanding the reactions of peri-implant bone. The aim of this study was to perform a histologic and histomorphometric analysis of the peri-implant tissues behavior and of the bone–titanium interface in titanium dental implants retrieved from patients after time periods longer than 5 years. The archives of the Implant Retrieval Center of the Dental School of the University of Chieti-Pescara, Italy were searched for human dental implants, retrieved after a loading period of more than 5 years. A total of 8 implants were found: 3 of these had been retrieved after 5 years, 1 after 6 years, one after 10 years, 1 after 14 years, 1 after 18 years, 1 after 22 years. Only the bone to implant contact in the three best threads was evaluated. Compact, mature, lamellar bone, with few and small marrow spaces, was present around the implants. Osteons with Haversian canals were present inside some threads, in close proximity to the interface, at both cortical and trabecular regions. Other osteons had a direction perpendicular to the direction of the long axis of the implants. Numerous reversal lines were present. At higher magnification, no gaps or fibrous, connective tissues were present at the interface. The BIC of the three best threads for all implants varied from 94 to 100 %.In conclusion, within the limitations of the present report histology showed that implants with different surfaces all presented the potential to maintain osseointegration over a long period, with a continuous remodeling at the interface, as indicated by the presence of reversal lines.