Diabetic Foot Disease: Emerging Technologies: Plantar Pressure Distribution Patterns of Individuals with Prediabetes in Comparison with Healthy Individuals and Individuals with Diabetes

Background

Since elevated mechanical stress along with loss of plantar protective sensation are considered relevant factors in skin breakdown resulting in diabetic foot ulcerations, the assessment of plantar pressure is important for the prevention of diabetic foot complications. Prediabetes subjects are at risk of chronic hyperglycemia complications, among them neuropathy, but information about plantar loading in this population is not available. We aimed to compare baropodometric parameters of individuals with prediabetes versus healthy persons and persons with diabetes mellitus (DM).

Methods

Baropodometric data from 73 subjects (15 with prediabetes (pre-DM), 28 with type 2 DM, 30 healthy) aged between 29 and 69 years of both genders were registered through a pressure platform with self-selected gait speed and first-step protocol. Peak plantar pressure, stance time, percentage of contact time, percentage of contact area and pressure-time integral were assessed in five plantar foot regions: heel, midfoot, metatarsals, hallux, and toes 2 to 5. Groups were compared by one-way analysis of variance with Scheffé post hoc (α = 0.05).

Results

Age, body mass index, gender, and arch height index did not differ between groups. Pre-DM and DM subjects presented increased peak pressure and pressure-time integral in metatarsals (p = .010; p > .001), as well as increased percentage of contact time in midfoot (p = .006) and metatarsals (p = .004) regions when compared with healthy subjects. Stance time was significantly higher (p = .017) in DM subjects.

Conclusions

Pre-DM subjects seem to exhibit an altered plantar pressure distribution pattern similar to that often found in DM subjects.     

Diabetic Foot Disease: Emerging Technologies: Repeatability of Infrared Plantar Thermography in Diabetes Patients: A Pilot Study

Objective

Infrared (IR) thermography has been used as a complementary diagnostic method in several pathologies, including distal diabetic neuropathy, by tests that induce thermoregulatory responses, but nothing is known about the repeatability of these tests. This study aimed to assess the repeatability of the rewarming index in subjects with type 2 diabetes mellitus (T2DM) and nondiabetic control subjects.

Methods

Using an IR camera, plantar IR images were collected at baseline (pre-) and 10 min after (post-) cold stress testing on two different days with 7 days interval. Plantar absolute average temperatures pre- and post-cold stress testing, the difference between them (ΔT), and the rewarming index were obtained and compared between days. Repeatability of the rewarming index after the cold stress test was assessed by Bland–Altman plot limits of agreement.

Results

Ten T2DM subjects and ten nondiabetic subjects had both feet analyzed. Mean age did not differ between groups (p = .080). Absolute average temperatures of plantar region pre- (p = .033) and post-cold stress test (p = .019) differed between days in nondiabetic subjects, whereas they did not differ in T2DM subjects (pretest, p = .329; post-test, p = .540). ΔT and rewarming index did not differ between days for both groups, and the rewarming index presented a 100% agreement of day-to-day measurements from T2DM subjects and 95% with nondiabetic subjects.

Conclusions

The rewarming index after cold stress testing presented good repeatability between two days a week in both groups. Despite T2DM subjects presenting no differences on absolute temperature values between days, ΔT or rewarming index after cold stress testing remain recommended beside absolute temperature values for clinical use.     

Plantar fascia thickness is longitudinally associated with retinopathy and renal dysfunction: a prospective study from adolescence to adulthood

Aim

The aim was to study the longitudinal relationship between plantar fascia thickness (PFT) as a measure of tissue glycation and microvascular (MV) complications in young persons with type 1 diabetes (T1DM).

Methods

We conducted a prospective longitudinal cohort study of 152 (69 male) adolescents with T1DM who underwent repeated MV complications assessments and ultrasound measurements of PFT from baseline (1997–2002) until 2008. Retinopathy was assessed by 7-field stereoscopic fundal photography and nephropathy by albumin excretion rate (AER) from three timed overnight urine specimens. Longitudinal analysis was performed using generalized estimating equations (GEE).

Results

Median (interquartile range) age at baseline was 15.1 (13.4–16.8) years, and median follow-up was 8.3 (7.0–9.5) years, with 4 (3–6) visits per patient. Glycemic control improved from baseline to final visit [glycated hemoglobin (HbA1c) 8.5% to 8.0%, respectively; p = .004]. Prevalence of retinopathy increased from 20% to 51% (p < .001) and early elevation of AER (>7.5 µg/min) increased from 26% to 29% (p = .2). A greater increase in PFT (mm/year) was associated with retinopathy at the final assessment (ΔPFT 1st vs. 2nd–4th quartiles, χ² = 9.87, p = .02). In multivariate GEE, greater PFT was longitudinally associated with retinopathy [odds ratio (OR) 4.6, 95% confidence interval (CI) 2.0–10.3] and early renal dysfunction (OR 3.2, CI 1.3–8.0) after adjusting for gender, blood pressure standard deviation scores, HbA1c, and total cholesterol.

Conclusions

In young people with T1DM, PFT was longitudinally associated with retinopathy and early renal dysfunction, highlighting the importance of early glycemic control and supporting the role of metabolic memory in MV complications. Measurement of PFT by ultrasound offers a noninvasive estimate of glycemic burden and tissue glycation.     

Correlation between plantar foot temperature and diabetic neuropathy: a case study by using an infrared thermal imaging technique

Background

Diabetic neuropathy consists of multiple clinical manifestations of which loss of sensation is most prominent. High temperatures under the foot coupled with reduced or complete loss of sensation can predispose the patient to foot ulceration. The aim of this study was to look at the correlation between plantar foot temperature and diabetic neuropathy using a noninvasive infrared thermal imaging technique.

Methods

Infrared thermal imaging, a remote and noncontact experimental tool, was used to study the plantar foot temperatures of 112 subjects with type 2 diabetes selected from a tertiary diabetes centre in South India.

Results

Patients with diabetic neuropathy (defined as vibration perception threshold (VPT) values on biothesiometry greater than 20 V) had a higher foot temperature (32–35 °C) compared to patients without neuropathy (27–30 °C). Diabetic subjects with neuropathy also had higher mean foot temperature (MFT) (p = .001) compared to non-neuropathic subjects. MFT also showed a positive correlation with right great toe (r = 0.301, p = .001) and left great toe VPT values (r = 0.292, p = .002). However, there was no correlation between glycated hemoglobin and MFT.

Conclusion

Infrared thermal imaging may be used as an additional tool for evaluation of high risk diabetic feet.     

Measurement of Intrahepatic Pressure during Microwave Ablation in an Ex Vivo Bovine Liver Model

Background/Aims

We experimented with different ablation methods and two types of microwave antennas to determine whether microwave ablation (MWA) increases intrahepatic pressure and to identify an MWA protocol that avoids increasing intrahepatic pressure.

Methods

MWA was performed using either a single-step standard ablation or a stepwise increment ablation paired with either a 16-gauge (G) 2-cm antenna or a 14G 4-cm antenna. We compared the maximum pressures and total ablation volumes.

Results

The mean maximum intrahepatic pressures and ablation volumes were as follows: 16G single-step: 37±33.4 mm Hg and 4.63 cm³; 16G multistep: 31±18.7 mm Hg and 3.75 cm³; 14G single-step: 114±45.4 mm Hg and 15.33 cm³; and 14G multistep: 106±43.8 mm Hg and 10.98 cm³. The intrahepatic pressure rose during MWA, but there were no statistically significant differences between the single and multistep methods when the same gauge antennae were used. The total ablation volume was different only in the 14G groups (p<0.05).

Conclusions

We demonstrated an increase in intrahepatic pressure during MWA. The multistep method may be used to prevent increased intrahepatic pressure after applying the proper power.     

Pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a French multicentre prospective evaluation of resection margins in 150 evaluable specimens

Objectives

This study aimed to determine the impact of a standardized pathological protocol on resection margin status after pancreaticoduodenectomy (PD) for ductal adenocarcinoma.

Methods

A total of 150 patients operated during 2008–2010 were included in a prospective multicentre study using a ‘quality protocol’. Multicolour inking by the surgeon identified three resection margins: the portal vein–superior mesenteric vein margin (PV-SMVm) or mesenterico–portal vein groove; the superior mesenteric artery margin (SMAm), and the posterior margin. Resection margins were stratified by 0.5-mm increments (range: 0–2.0 mm). Pancreatic neck, bile duct and intestinal margins were also analysed. Correlations between histopathological factors and survival in the 0-mm resection margin group were analysed.

Results

Thirty-six patients (24%) had a PV-SMV resection (PV-SMVR). An analysis of resections categorized according to margin distances of 0 mm, <1.0 mm, <1.5 mm and <2.0 mm confirmed R1 resections in 35 (23%), 91 (61%), 94 (63%) and 107 (71%) patients, respectively. The most frequently invaded resection margin was the PV-SMVm (35% of all patients) and PV-SMVR was the only factor correlated with a higher risk for at least one 0-mm positive resection margin on multivariate analysis (P < 0.001). Two-year progression-free survival (PFS) and median PFS time in patients with R0 and R1 resections (at 0 mm), respectively, were 42.0% and 26.5%, and 19.5 months and 10.5 months, respectively (P = 0.02). A positive PV-SMVm and SMAm had significant impact on PFS, whereas a positive posterior margin had no impact.

Conclusions

Pancreaticoduodenectomy requiring PV-SMVR was associated with a higher risk for R1 resection. The standardization of histopathological analysis has a clinically relevant impact on PFS data.     

Continuous Monitoring of Glucose in Subcutaneous Tissue Using Microfabricated Differential Affinity Sensors

Objective

We describe miniaturized differential glucose sensors based on affinity binding between glucose and a synthetic polymer. The sensors possess excellent resistance to environmental disturbances and can potentially allow wireless measurements of glucose concentrations within interstitial fluid in subcutaneous tissue for long-term, stable continuous glucose monitoring (CGM).

Methods

The sensors are constructed using microelectromechanical systems (MEMS) technology and exploit poly(N-hydroxy-ethyl acrylamide-ran-3-acrylamidophenylboronic acid) (PHEAA-ran-PAAPBA), a glucose-binding polymer with excellent specificity, reversibility, and stability. Two sensing approaches have been investigated, which respectively, use a pair of magnetically actuated diaphragms and perforated electrodes to differentially measure the glucose-binding-induced changes in the viscosity and permittivity of the PHEAA-ran-PAAPBA solution with respect to a reference, glucose-unresponsive polymer solution.

Results

In vivo characterization of the MEMS affinity sensors were performed by controlling blood glucose concentrations of laboratory mice by exogenous glucose and insulin administration. The sensors experienced an 8–30 min initialization period after implantation and then closely tracked commercial capillary glucose meter readings with time lags ranging from 0–15 min during rapid glucose concentration changes. Clarke error grid plots obtained from sensor calibration suggest that, for the viscometric and dielectric sensors, respectively, approximately 95% (in the hyperglycemic range) and 84% (ranging from hypoglycemic to hyperglycemic glucose concentrations) of measurement points were clinically accurate, while 5% and 16% of the points were clinically acceptable.

Conclusions

The miniaturized MEMS sensors explore differential measurements of affinity glucose recognition. In vivo testing demonstrated excellent accuracy and stability, suggesting that the devices hold the potential to enable long-term and reliable CGM in clinical applications.     

Enhanced recovery following liver surgery: a systematic review and meta-analysis

Background

Enhanced recovery after surgery (ERAS) programmes aim to improve postoperative outcomes. They are being utilized increasingly in hepatic surgery. This review aims to evaluate the impact of ERAS programmes on outcomes following liver surgery.

Methods

EMBASE, MEDLINE, PubMed and the Cochrane Database were searched for trials comparing outcomes in patients undergoing liver surgery utilizing ERAS principles with those in patients receiving conventional care. The primary outcome was occurrence of postoperative complications within 30 days. Secondary outcomes included length of stay (LoS), functional recovery and adherence to ERAS protocols.

Results

Nine articles were included in the review, of which two were randomized controlled trials (RCTs). Overall complication rates were 25.0% (range: 11.5–46.4%) in ERAS patients, and 31.0% (range: 11.8–46.2%) in conventional care patients. Significantly reduced overall complication rates following ERAS care were demonstrated by a meta-analysis of the data reported in the two RCTs (odds ratio: 0.49, 95% confidence interval 0.28–0.84; P = 0.01) The median LoS reported by the studies was 5.0 days (range: 2.5–7.0 days) in ERAS patients, and 7.5 days (range: 3.0–11.0 days) in non-ERAS patients. Recovery milestones, when reported, were improved following ERAS care.

Conclusions

The adoption of ERAS protocols improves morbidity and LoS following liver surgery. Future ERAS programmes should accommodate the unique requirements of liver surgery in order to optimize postoperative outcomes.     

Role of quantification of hepatic steatosis and future remnant volume in predicting hepatic dysfunction and complications after liver resection for colorectal metastases: a pilot study

Objectives

Accurate prediction of safe remnant liver volume to minimize complications following liver resection remains challenging. The aim of this study was to assess whether quantification of steatosis improved the predictive value of preoperative volumetric analysis.

Methods

Thirty patients undergoing planned right or extended right hemi-hepatectomy for colorectal metastases were recruited prospectively. Magnetic resonance imaging was used to assess the level of hepatic steatosis and future remnant liver volume. These data were correlated with data on postoperative hepatic insufficiency, complications and hospital stay. Correlations of remnant percentage, remnant mass to patient mass and remnant mass to body surface area with and without steatosis measurements were assessed.

Results

In 10 of the 30 patients the planned liver resection was altered. Moderate–severe postoperative hepatic dysfunction was seen in 17 patients. Complications arose in 14 patients. The median level of steatosis was 3.8% (range: 1.2–17.6%), but was higher in patients (n= 10) who received preoperative chemotherapy (P= 0.124), in whom the median level was 4.8% (range: 1.5–17.6%). The strongest correlation was that of remnant liver mass to patient mass (r= 0.77, P < 0.001). However, the addition of steatosis quantification did not improve this correlation (r= 0.76, P < 0.001).

Conclusions

This is the first study to combine volumetric with steatosis quantifications. No significant benefit was seen in this small pilot. However, these techniques may be useful in operative planning, particularly in patients receiving preoperative chemotherapy.     

Circulating adiponectin levels and risk of type 2 diabetes in the Japanese

Background:

Adiponectin has anti-inflammatory and insulin-sensitizing properties. Prospective studies have consistently shown a lower risk of type 2 diabetes among those with higher circulating adiponectin levels.

Objective:

We examined prospectively the association between serum adiponectin levels and type 2 diabetes risk among Japanese workers, taking visceral fat mass into account.

Subjects and methods:

Subjects were 4591 Japanese employees who attended a comprehensive health screening in 2008; had biochemical data including serum adiponectin; were free of diabetes at baseline; and received health screening in 2011. Multiple logistic regression analysis was used to examine the association between adiponectin and incidence of diabetes among overall subjects, as well as subgroups. Stratified analyses were carried out according to variables including visceral fat area (VFA).

Results:

During 3 years of follow-up, 217 diabetic cases were newly identified. Of these, 87% had a prediabetes at baseline. Serum adiponectin level was significantly, inversely associated with incidence of diabetes, with odds ratios (95% confidence interval) adjusted for age, sex, family history, smoking, alcohol drinking, physical activity and body mass index (BMI) for the lowest through highest quartile of adiponectin of 1 (reference), 0.79 (0.55–1.12), 0.60 (0.41–0.88) and 0.40 (0.25–0.64), respectively (P-value for trend <0.01). This association was materially unchanged with adjustment for VFA instead of BMI. After further adjustment for both homeostasis model assessment of insulin resistance and hemoglobin A1c, however, the association became statistically nonsignificant (P-value for trend=0.18). Risk reduction associated with higher adiponectin levels was observed in both participants with and without obesity or insulin resistance at baseline.

Conclusions:

Results suggest that higher levels of circulating adiponectin are associated with a lower risk of type 2 diabetes, independently of overall and intra-abdominal fat deposition, and that adiponectin may confer a benefit in both persons with and without insulin resistance.     

The Risk Factors for Bleeding of Fundal Varices in Patients with Liver Cirrhosis

Background/Aims

The relationship between portal hemodynamics and fundal varices has not been well documented. The purpose of this study was to understand the pathophysiology of fundal varices and to investigate bleeding risk factors related to the presence of spontaneous portosystemic shunts, and to examine the hepatic venous pressure gradient (HVPG) between fundal varices and other varices.

Methods

In total, 85 patients with cirrhosis who underwent HVPG and gastroscopic examination between July 2009 and March 2011 were included in this study. The interrelationship between HVPG and the types of varices or the presence of spontaneous portosystemic shunts was studied.

Results

There was no significant difference in the HVPG between fundal varices (n=12) and esophageal varices and gastroesophageal varices type 1 (GOV1) groups (n=73) (17.1±7.7 mm Hg vs 19.7±5.3 mm Hg). Additionally, there was no significant difference in the HVPG between varices with spontaneous portosystemic shunts (n=28) and varices without these shunts (n=57) (18.3±5.8 mm Hg vs 17.0±8.1 mm Hg). Spontaneous portosystemic shunts increased in fundal varices compared with esophageal varices and GOV1 (8/12 patients [66.7%] vs 20/73 patients [27.4%]; p=0.016).

Conclusions

Fundal varices had a high prevalence of spontaneous portosystemic shunts compared with other varices. However, the portal pressure in fundal varices was not different from the pressure in esophageal varices and GOV1.     

Renal sympathetic denervation using an externally irrigated radiofrequency ablation catheter for treatment of resistant hypertension – Acute safety and short term efficacy

Objectives

This study was conducted to assess the acute safety and short term efficacy of renal sympathetic denervation (RSDN) using solid tip radiofrequency ablation (RFA) catheter and saline irrigation through the renal guiding catheter to achieve effective denervation.

Background

RSDN using a specialized solid-tip RFA catheter has recently been demonstrated to safely reduce systemic blood pressure in patients with refractory hypertension, the limitation being inadequate power delivery in renal arteries. So, we used solid-tip RFA catheter along with saline irrigation for RSDN.

Methods

Nine patients with resistant hypertension underwent CT and conventional renal angiography, followed by bilateral or unilateral RSDN using 5F RFA catheter with saline irrigation through renal guiding catheter. Repeat renal angiography was performed at the end of the procedure. In all patients, pre- and post-procedure serum creatinine was measured.

Results

Over 1-month period: 1) the systolic/diastolic blood pressure decreased by −57 ± 20/−25 ± 7.5 mm Hg; 2) all patients experienced a decrease in systolic blood pressure of at least −36 mm Hg (range 36–98 mm Hg); 3) there was no evidence of renal artery injury immediate post-procedure. There was no significant change in serum creatinine level.

Conclusions

This data shows the acute procedural safety and short term efficacy of RSDN using modified externally irrigated solid tip RFA catheter.     

Tumour size over 3 cm predicts poor short-term outcomes after major liver resection for hilar cholangiocarcinoma. By the HC-AFC-2009 group

Introduction

As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection.

Methods

Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study''s objective was to identify pre-operative predictors of early death (<12 months) after a resection.

Results

The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24–85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136–7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038–10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis.

Conclusion

The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months.     

"Smart tattoo" glucose biosensors and effect of coencapsulated anti-inflammatory agents

Background

Minimally invasive glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring. In the present study, we developed a novel nanoengineered microsphere formulation comprising alginate microsphere glucose sensors and anti-inflammatory-drug-loaded alginate microspheres.

Methods

The formulation was prepared and characterized for size, shape, in vitro drug release, biocompatibility, and in vivo acceptability. Glucose oxidase (GOx)- and Apo-GOx-based glucose sensors were prepared and characterized. Sensing was performed both in distilled water and simulated interstitial body fluid. Layer-by-layer self-assembly techniques were used for preventing drug and sensing chemistry release. Finally, in vivo studies, involving histopathologic examination of subcutaneous tissue surrounding the implanted sensors using Sprague–Dawley rats, were performed to test the suppression of inflammation and fibrosis associated with glucose sensor implantation.

Results

The drug formulation showed 100% drug release with in 30 days with zero-order release kinetics. The GOx-based sensors showed good enzyme retention and enzyme activity over a period of 1 month. Apo-GOx-based visible and near-infrared sensors showed good sensitivity and analytical response range of 0–50 mM glucose, with linear range up to 12 mM glucose concentration. In vitro cell line studies proved biocompatibility of the material used. Finally, both anti-inflammatory drugs were successful in controlling the implant–tissue interface by suppressing inflammation at the implant site.

Conclusion

The incorporation of anti-inflammatory drug with glucose biosensors shows promise in improving sensor biocompatibility, thereby suggesting potential application of alginate microspheres as “smart tattoo” glucose sensors with increased functional longevity.     

Initial experiences in robot-assisted middle pancreatectomy

Objectives

Initial results in robot-assisted middle pancreatectomy (MP) have been encouraging. However, data comparing outcomes of robot-assisted MP with those of open MP are limited. The aim of this study was to compare outcomes in patients undergoing open and robot-assisted MP, respectively.

Methods

Outcomes in an initial experience with seven consecutive patients undergoing robot-assisted MP were compared with those in 36 patients undergoing open MP.

Results

The robot-assisted MP group included five women and two men with a median age of 55 years (range: 30–62 years). Median tumour size, operative time and blood loss were 3.0 cm (range: 0.5–5.0 cm), 210 min (range: 150–330 min) and 200 ml (range: 50–400 ml), respectively. Pancreaticogastrostomy was performed in all patients. No transfusion was given intraoperatively. Pathological examination revealed five serous cystic neoplasms, one mixed-type intraductal papillary mucinous neoplasm and one lipoma. Five patients experienced postoperative pancreatic fistula and one experienced post-pancreatectomy haemorrhage. No operative mortality was noted. Compared with the open MP group, the robot-assisted MP group demonstrated a shorter median length of postoperative gastrointestinal tract recovery [2 days (range: 2–3 days) versus 4 days (range: 2–11 days); P = 0.001].

Conclusions

Robot-assisted MP can be performed safely with satisfactory efficacy; patients experienced faster gastrointestinal tract recovery compared with patients undergoing open surgery.     

Survival Trends of US Dialysis Patients with Heart Failure: 1995 to 2005

Summary

Background and objectives

Congestive heart failure (CHF) is a major risk factor for death in end-stage kidney disease; however, data on prevalence and survival trends are limited. The objective of this study was to determine the prevalence and mortality effect of CHF in successive incident dialysis cohorts.

Design, setting, participants, & measurements

This was a population-based cohort of incident US dialysis patients (n = 926,298) from 1995 to 2005. Age- and gender-specific prevalence of CHF was determined by incident year, whereas temporal trends in mortality were compared using multivariable Cox regression.

Results

The prevalence of CHF was significantly higher in women than men and in older than younger patients, but it did not change over time in men (range 28% to 33%) or women (range 33% to 36%). From 1995 to 2005, incident death rates decreased for younger men (≤70 years) and increased for older men (>70 years). For women, the pattern was similar but less impressive. During this period, the adjusted mortality risks (relative risk [RR]) from CHF decreased in men (from RR = 1.06 95% Confidence intervals (CI) 1.02–1.11 in 1995 to 0.91 95% CI 0.87–0.96 in 2005) and women (from RR = 1.06 95% CI 1.01–1.10 in 1995 to 0.90 95% CI 0.85–0.95 in 2005 compared with referent year 2000; RR = 1.00). The reduction in mortality over time was greater for younger than older patients (20% to 30% versus 5% to 10% decrease per decade).

Conclusions

Although CHF remains a common condition at dialysis initiation, mortality risks in US patients have declined from 1995 to 2005.     

Is tumour size an underestimated feature in the current TNM system for malignancies of the pancreatic head?

Background

As the long-term survival of pancreatic head malignancies remains dismal, efforts have been made for a better patient selection and a tailored treatment. Tumour size could also be used for patient stratification.

Methods

One hundred and fourteen patients underwent a pancreaticoduodenectomy for pancreatic adenocarcinoma, peri-ampullary and biliary cancer stratified according to: ≤20 mm, 21–34 mm, 35–45 mm and >45 mm tumour size.

Results

Patients with tumour sizes of ≤20 mm had a N1 rate of 41% and a R1/2 rate of 7%. The median survival was 3.4 years. N1 and R1/2 rates increased to 84% and 31% for tumour sizes of 21–34 mm (P = 0.0002 for N, P = 0.02 for R). The median survival decreased to 1.6 years (P = 0.0003). A further increase in tumour size of 35–45 mm revealed a further increase of N1 and R1/2 rates of 93% (P < 0.0001) and 33%, respectively. The median survival was 1.2 years (P = 0.004). Tumour sizes >45 mm were related to a further decreased median survival of 1.1 years (P = 0.2), whereas N1 and R1/2 rates were 87% and 20%, respectively.

Discussion

Tumour size is an important feature of pancreatic head malignancies. A tumour diameter of 20 mm seems to be the cut-off above which an increased rate of incomplete resections and metastatic lymph nodes must be encountered and the median survival is reduced.     

Asymmetric and Symmetric Dimethylarginine and Sympathetic Nerve Traffic after Renal Denervation in Patients with Resistant Hypertension

Background and objectives

The plasma concentration of the endogenous inhibitor of nitric oxide synthase asymmetric dimethylarginine (ADMA) associates with sympathetic activity in patients with CKD, but the driver of this association is unknown.

Design, setting, participants, & measurements

In this longitudinal study (follow-up: 2 weeks–6 months), repeated measurements over time of muscle sympathetic nerve activity corrected (MSNAC), plasma levels of ADMA and symmetric dimethylarginine (SDMA), and BP and heart rate were performed in 14 patients with drug-resistant hypertension who underwent bilateral renal denervation (enrolled in 2013 and followed-up until February 2014). Stability of ADMA, SDMA, BP, and MSNAC over time (6 months) was assessed in two historical control groups of patients maintained on stable antihypertensive treatment.

Results

Time-integrated changes in MSNAC after renal denervation ranged from –40.6% to 10% (average, –15.1%), and these changes were strongly associated with the corresponding changes in plasma ADMA (r= 0.62, P=0.02) and SDMA (r=0.72, P=0.004). Changes in MSNAC went along with simultaneous changes in standardized systolic (r=0.65, P=0.01) and diastolic BP (r=0.61, P=0.02). In the historical control groups, no change in ADMA, SDMA, BP, and MSNAC levels was recorded during a 6-month follow-up.

Conclusions

In patients with resistant hypertension, changes in sympathetic activity after renal denervation associate with simultaneous changes in plasma levels of the two major endogenous methylarginines, ADMA and SDMA. These observations are compatible with the hypothesis that the sympathetic nervous system exerts an important role in modulating circulating levels of ADMA and SDMA in this condition.     

Pharmacokinetics of Insulin Aspart and Glucagon in Type 1 Diabetes during Closed-Loop Operation

Background

We assessed the pharmacokinetics of subcutaneous insulin aspart and glucagon during closed-loop operation and their relationship with body composition variables.

Methods

We retrospectively analyzed data collected from closed-loop experiments in 15 type 1 diabetes patients (age 47.1 ± 12.3 years, body mass index 25.9 ± 4.6 kg/m², glycated hemoglobin 7.9% ± 0.7%). Patients received an evening meal accompanied with prandial insulin bolus and stayed in the clinical facility until the next morning. Glucose levels were regulated by dual-hormone closed-loop delivery. Insulin and glucagon were delivered using two subcutaneous infusion pumps installed on the abdominal wall. Plasma insulin and glucagon were measured every 10–30 min. Percentage of body fat, percentage of fat in the abdominal area, and mass of abdominal fat were measured by dual X-ray absorptiometry.

Results

A pharmacokinetic model estimated time-to-peak plasma concentrations [t_max insulin 51 (19) min, t_max glucagon 19 (4) min, mean (standard deviation)], metabolic clearance rate [MCR insulin 0.019 (0.015–0.026) liter/kg/min, MCR glucagon 0.012 (0.010–0.014) liter/kg/min, median (interquartile range)], and the background plasma concentrations [I_b insulin 10.2 (6.3–15.2) mU/liter, I_b glucagon 50 (45–56) pg/ml, median (interquartile range)]. t_max correlated positively between insulin and glucagon (r = 0.7; p = .007) while MCR correlated negatively (r = -0.7; p = .015). In this small sample size, t_max, MCR, and I_b of insulin and glucagon did not correlate with percentage of body fat, percentage of fat in the abdominal area, or total mass of abdominal fat.

Conclusions

Insulin and glucagon pharmacokinetics might be related during closed-loop operation. Our data suggest that slower absorption of insulin is associated with slower absorption of glucagon. Body composition does not seem to influence insulin and glucagon pharmacokinetics.