Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome

Aims/hypothesis

We sought to establish the molecular and pathological changes predisposing diabetic and non-diabetic patients to the development of carpal tunnel syndrome (CTS).

Methods

The posterior interosseous nerve (PIN) was biopsied in 25 diabetic and 19 non-diabetic patients undergoing carpal tunnel decompression for CTS. Detailed morphometric and immunohistological analyses were performed in the nerve biopsy.

Results

In diabetic patients median nerve distal motor latency was prolonged (p?<?0.05 vs non-diabetic patients), PIN myelinated fibre density (p?<?0.05), fibre area (p?<?0.0001) and axon area (p?<?0.0001) were reduced, the percentage of unassociated Schwann cell profiles (p?<?0.0001) and unmyelinated axon density (p?<?0.0001) were increased and the axon diameter was reduced (p?<?0.0001). Endoneurial capillary basement membrane area was increased (p?<?0.0001) in diabetic patients, but endothelial cell number was increased (p?<?0.01) and luminal area was reduced (p?<?0.05) in non-diabetic patients with CTS. There was no difference in the expression of hypoxia-inducible factor 1α between diabetic and non-diabetic patients with CTS. However, the expression of vascular endothelial growth factor A (VEGF) (p?<?0.05) and its receptors VEGFR-1 (p?<?0.01) and VEGFR-2 (p?<?0.05) was significantly increased in diabetic patients, particularly those with type 1 diabetes, and related to the severity of nerve fibre pathology.

Conclusions/interpretation

This study demonstrates increased nerve fibre and microvascular pathology in relation to enhanced expression of VEGF and its receptors in a non-compressed nerve in diabetic compared with non-diabetic patients with CTS. It therefore provides a potential molecular and pathological basis for the predisposition of diabetic patients to the development of CTS.     

Relationship Between Quantitative CT Metrics and Pulmonary Function in Combined Pulmonary Fibrosis and Emphysema

Purpose

Combined pulmonary fibrosis and emphysema (CPFE) is increasingly recognized, as current reports of its clinical features show. To determine CPFE’s physiologic and radiologic features, we conducted quantitative assessment of computed tomography scans to compare with those of chronic obstructive pulmonary disease (COPD).

Methods

In 23 patients with CPFE and 42 patients with COPD, we measured the extent of emphysema (LAA %), parenchymal density, and total cross-sectional areas of pulmonary vessels smaller than 5 mm² (%CSA <5) and 5–10 mm² (%CSA 5–10).

Results

For CPFE, airflow was better, but diffusing capacity for carbon monoxide (DL_CO) was worse than for COPD, whereas LAA % was similar for both groups. The %CSA <5 was greater but %CSA5–10 was less in CPFE than COPD. COPD involved a negative correlation between DL_CO and LAA % at all lung sites; those factors correlated for CPFE only in the upper lobe (r = ?0.535). In contrast, CPFE had a negative correlation between DL_CO and parenchymal density in lower lobes (r = ?0.453), but COPD showed no correlation in any such sections. In CPFE, no correlation was apparent between LAA in upper lobes and parenchymal density in lower lobes. The annual rate of FVC decline (?169.26 ml/year) in CPFE patients correlated with parenchymal density (r = ?0.714).

Conclusions

In CPFE, fibrosis and emphysema apparently existed independently, but both correlate with and likely contribute to the disproportionate reduction in gas exchange. Our study also suggested that pulmonary fibrotic changes may be more important contributors than emphysema for disease progression.     

Association Between CD4<Superscript>+</Superscript>, Viral Load,and Pulmonary Function in HIV

Purpose

The antiretroviral therapy era has shifted the epidemiology of HIV-associated diseases, increasing the recognition of non-infectious pulmonary complications secondary to HIV. We aimed to determine the association between CD4⁺, viral load, and pulmonary function in individuals with uncontrolled HIV, and determine how changes in these parameters are associated with pulmonary function longitudinally.

Methods

This is a retrospective observational study of individuals with HIV who underwent pulmonary function testing in an urban medical center between August 1997 and November 2015.

Results

Of the 146 participants (mean age 52 ± 10 years), 49% were Hispanic, 56% were men, and 44% were current smokers. CD4⁺ <200 cells/μl was associated with significant diffusion impairment compared to CD4⁺ ≥200 cells/μl (DL_CO 56 vs. 70%, p = <0.01). VL (viral load) ≥75 copies/ml was associated with significant diffusion impairment compared to VL <75 copies/ml (DL_CO 60 vs. 71%, p = <0.01). No difference in FEV1, FEV1/FVC, or TLC was noted between groups. In univariate analysis, CD4⁺ and VL correlated with DL_CO (r = +0.33; p = <0.01; r = ?0.26; p = <0.01) and no correlation was noted with FEV₁, FEV₁/FVC, or TLC. Current smoking and history of AIDS correlated with DL_CO (r = ?0.20; p = 0.03; r = ?0.20; p = 0.04). After adjusting for smoking and other confounders, VL ≥75 copies/ml correlated with a 11.2 (CI 95% [3.03–19.4], p = <0.01) decrease in DL_CO. In Spearman’s Rank correlation, there was a negative correlation between change in VL and change in DL_CO over time (ρ = ?0.47; p = <0.01).

Conclusion

The presence of viremia in individuals with HIV is independently associated with impaired DL_CO. Suppression of VL may allow for recovery in diffusing capacity over time, though the degree to which this occurs requires further investigation.

     

Diabetic ketoacidosis at the onset of type 1 diabetes is associated with future HbA1c levels

Aims/hypothesis

We investigated the long-term impact of diabetic ketoacidosis (DKA) at onset on metabolic regulation and residual beta cell function in a Danish population with type 1 diabetes.

Methods

The study is based on data from DanDiabKids, a Danish national diabetes register for children. The register provides clinical and biochemical data on patients with type 1 diabetes diagnosed in 1996–2009 and then followed-up until 1 January 2012. Repeated-measurement models were used as statistical methods.

Results

The study population comprised 2,964 children <18 years. The prevalence of DKA at diagnosis was 17.9%. Of the total subjects, 8.3% had mild, 7.9% had moderate and 1.7% had severe DKA. DKA (moderate and severe) was associated with increased HbA_1c (%) levels (0.24; 95% CI 0.11, 0.36; p?=?0.0003) and increased insulin dose-adjusted HbA_1c (IDAA_1c, 0.51; 95% CI 0.31, 0.70; p?<?0.0001) during follow-up, after adjustment for covariates. Children without a family history of diabetes were more likely to present with DKA (19.2% vs 8.8%, p?<?0.0001); however, these children had a lower HbA_1c (%) level over time (?0.35; 95% CI ?0.46, ?0.24; p?<?0.0001). Continuous subcutaneous insulin infusion (CSII) was associated with a long-term reduction in HbA_1c, changing the effect of DKA, after adjustment for covariates (p?<?0.0001).

Conclusions/interpretation

DKA at diagnosis was associated with poor long-term metabolic regulation and residual beta cell function as assessed by HbA_1c and IDAA_1c, respectively; however, CSII treatment was associated with improvement in glycaemic regulation and residual beta cell function, changing the effect of DKA at onset in our population.     

Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice

Aims/hypothesis

Cholecystokinin (CCK) and leptin are important hormones with effects on energy balance. The present study assessed the biological effects of (pGlu-Gln)-CCK-8 and [d-Leu-4]-OB3, smaller isoforms of CCK and leptin, respectively.

Methods

The actions and overall therapeutic use of (pGlu-Gln)-CCK-8 and [d-Leu-4]-OB3, alone and in combination, were evaluated in normal and high-fat-fed mice.

Results

(pGlu-Gln)-CCK-8 had prominent (p?<?0.01 to p?<?0.001), acute feeding-suppressive effects, which were significantly augmented (p?<?0.05 to p?<?0.01) by [d-Leu-4]-OB3. In agreement, the acute dose-dependent glucose-lowering and insulinotropic actions of (pGlu-Gln)-CCK-8 were significantly enhanced by concurrent administration of [d-Leu-4]-OB3. Twice daily injection of (pGlu-Gln)-CCK-8 alone and in combination with [d-Leu-4]-OB3 in high-fat-fed mice for 18 days decreased body weight (p?<?0.05 to p?<?0.001), energy intake (p?<?0.01), circulating triacylglycerol (p?<?0.01), non-fasting glucose (p?<?0.05 to p?<?0.001) and triacylglycerol deposition in liver and adipose tissue (p?<?0.001). All treatment regimens improved glucose tolerance (p?<?0.05 to p?<?0.001) and insulin sensitivity (p?<?0.001). Combined treatment with (pGlu-Gln)-CCK-8 and [d-Leu-4]-OB3 resulted in significantly lowered plasma insulin levels, normalisation of circulating LDL-cholesterol and decreased triacylglycerol deposition in muscle. These effects were superior to either treatment regimen alone. There were no changes in overall locomotor activity or respiratory exchange ratio, but treatment with (pGlu-Gln)-CCK-8 significantly reduced (p?<?0.001) energy expenditure.

Conclusions/interpretation

These studies highlight the potential of (pGlu-Gln)-CCK-8 alone and in combination with [d-Leu-4]-OB3 in the treatment of obesity and diabetes.     

Validity of sheet-type portable monitoring device for screening obstructive sleep apnea syndrome

Purpose

The SD-101 is a non-restrictive sheet-like medical device that measures sleep-disordered breathing using pressure sensors that can detect the gravitational alterations in the body that accompany respiratory movement. One report has described that the screening specificity of the SD-101 for mild to moderate obstructive sleep apnea syndrome (OSAS) is relatively low. The present study examines whether the accuracy of the SD-101 for OSAS screening is improved by simultaneously measuring percutaneous oxygen saturation (SpO₂).

Methods

Sixty consecutive individuals with suspected OSAS consented to undergo overnight polysomnography (PSG) together with simultaneous measurements of SD-101 and SpO₂ at our laboratory.

Results

The apnea–hypopnea index (AHI) determined from PSG and the respiratory disturbance index determined from SD-101 measurements significantly correlated (SD-101 alone: r?=?0.871, p?<?0.0001; SD-101 with SpO₂: r?=?0.965, p?<?0.0001). Bland–Altman plots showed a smaller dispersion for the SD-101 with SpO₂ than for the SD-101 alone. The SD-101 with SpO₂ detected an AHI of >15 on PSG with a sensitivity and specificity of 96.9 and 90.5 % compared with 87.5 and of 85.7 %, respectively, of the SD-101 alone.

Conclusions

Simultaneously measuring SpO₂ improved the accuracy of the SD-101 for OSAS screening. Furthermore, this modality appears to offer high sensitivity and specificity for detecting even moderately severe OSAS.     

Surrogate end points for survival in the target treatment of advanced non-small-cell lung cancer with gefitinib or erlotinib

Background

It is controversial for the use of survival surrogate end points including response rate (RR), disease control rate (DCR), time to progression, and progression-free survival (PFS) in trials of molecular targeted agents. Our aim was to determine the correlations of these surrogates with survival in the treatment of advanced non-small-cell lung cancer (ANSCLC) with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib.

Methods

Summary data of median survival time (MST) and surrogates from prospective trials of EGFR-TKIs in ANSCLC were identified. Patient- or trial-related characteristics were introduced as covariates. Simple and multivariate linear regression models were fitted for MST and each surrogate, respectively. And the significance of each surrogate as a survival marker was compared by calculating the area under their receiver operating characteristic (ROC) curves.

Results

Sixty eligible trials (9,903 patients) were enrolled. RR, DCR, and PFS were all strongly associated with MST. In their simple linear regression models, the coefficient of determination (R ²) was 0.83 (p?<?0.000001), 0.58 (p?<?0.0001), and 0.70 (p?<?0.0001), respectively. And in their multivariate linear regression models, the standard coefficient was 0.71 (p?<?0.001), 0.40 (p?<?0.001), and 0.74 (p?<?0.001), respectively, while RR and PFS were the preferred survival predictors in the ROC analysis.

Conclusion

RR or PFS may serve as an appropriate survival surrogate in the clinical trials of EGFR-TKIs for ANSCLC.     

Randomised clinical trial of pilonidal sinus operations performed in the prone position under spinal anaesthesia with hyperbaric bupivacaine 0.5 % versus total intravenous anaesthesia

Purpose

The aim of this randomised clinical trial was to determine whether spinal anaesthesia (SPA) is superior to total intravenous anaesthesia (TIVA) in patients undergoing pilonidal sinus (PS) operations in the prone position.

Methods

After approval of the local ethics committee, suitable patients aged 19–49 years were randomised to SPA (7.5 mg hyperbaric bupivacaine) or TIVA (Propofol and Fentanyl). Cumulative consumption of analgesics, postoperative recovery, complications and patient satisfaction were evaluated.

Results

A total of 50 patients were randomised within a 24-month period. Median monitoring time in the recovery room was 0 (0–11)?min for SPA versus 40 (5–145)?min for TIVA (p?<?0.0001). Patients in the SPA group were able to drink (40.5 (0–327)?min versus TIVA 171 (72–280)?min, p?<?0.0001) and eat (55 (0–333)?min versus TIVA 220 (85–358), p?<?0.0001) earlier. More patients with a TIVA needed analgesics in the recovery room (SPA n?=?0 versus TIVA n?=?6, p?=?0.0023) and suffered more frequently from a sore throat (SPA n?=?0 versus TIVA n?=?11, p?=?0.0001). Two patients with a TIVA suffered from nausea and vomiting. Patients of both groups were equally satisfied with the anaesthesia technique offered.

Conclusions

SPA with 7.5 mg hyperbaric bupivacaine is superior to TIVA in patients undergoing PS operations in the prone position in terms of analgesia consumption in the recovery room, recovery times and postoperative complications.     

Low transition rate from normo- and low microalbuminuria to proteinuria in Japanese type 2 diabetic individuals: the Japan Diabetes Complications Study (JDCS)

Aims/hypothesis

The aim of the study was to determine the transition rate and factors associated with the progression of normo- and low microalbuminuria to diabetic nephropathy (overt proteinuria).

Methods

For 8?years we prospectively observed 1,558 Japanese patients with type 2 diabetes mellitus whose basal urinary albumin:creatinine ratio (UACR) had been measured as <17.0?mg/mmol at entry. The incidence of nephropathy (UACR >33.9?mg/mmol) was determined by measuring UACR twice a year.

Results

Progression to nephropathy occurred in 74 patients. The annual transition rate was 0.67%, and was substantially higher for the low-microalbuminuric group than for the normoalbuminuric group (1.85% and 0.23%, respectively; hazard ratio for the low-microalbuminuric group 8.45, p?<?0.01). The hazard ratio for an HbA_1c of 7?C9% or ??9% was 2.72 (p?<?0.01) or 5.81 (p?<?0.01) relative to HbA_1c <7.0%, respectively. In comparison with individuals with a systolic blood pressure (SBP) of <120?mmHg, the hazard ratios for patients with an SBP of 120?C140?mmHg or ??140?mmHg were 2.31 (p?=?0.06) and 3.54 (p?<?0.01), respectively. Smoking also affected progression to proteinuria (hazard ratio 1.99, p?<?0.01). In contrast, 30.3% of the low-microalbuminuric group returned to normoalbuminuria (i.e. were in remission).

Conclusions/interpretation

These results suggest that if patients with type 2 diabetes mellitus are receiving treatment from diabetologists for hyperglycaemia and hypertension when they are in the early stages of nephropathy (i.e. normo- or low microalbuminuria), their rate of transition to proteinuria is considerably lowered, and that differentiating patients with low microalbuminuria from those with high microalbuminuria might be clinically useful.

Trial registration

UMIN Clinical Trials Registry C000000222

Funding

The study was funded by the Ministry of Health, Labour and Welfare, Japan.     

Pro- and anti-inflammatory cytokines in latent autoimmune diabetes in adults, type 1 and type 2 diabetes patients: Action LADA 4

Aims/hypothesis

Systemic pro- and anti-inflammatory cytokines are associated with both type 1 and type 2 diabetes, while their role in latent autoimmune diabetes in adults (LADA) is unclear. Therefore, we compared cytokine concentrations in patients with LADA, type 1 or type 2 diabetes and healthy individuals to test the hypothesis that differences of cytokine concentrations between all groups are attributable to diabetes type and BMI.

Methods

The pro-inflammatory cytokines IL-6 and TNF-??, and the anti-inflammatory cytokines IL-1 receptor antagonist (IL-1RA) and IL-10 were measured in 90 participants with type 1 diabetes, 61 with LADA, 465 with type 2 diabetes and 41 control participants using multiple regression models adjusted for BMI, sex, age, blood pressure and diabetes duration.

Results

Patients with type 2 diabetes had higher concentrations of systemic IL-1RA, IL-6 and TNF-?? cytokines than patients with either LADA or type 1 diabetes (p?<?0.0001 for all differences). Cytokine concentrations in controls were lower than those in all diabetes types (p?<?0.04). Increased BMI was positively associated with higher systemic cytokine concentrations in all diabetes types (p?<?0.0001). Despite the association of cytokines with anthropometric data, differences between diabetes forms persisted also after adjusting analysis for the confounders BMI, age, sex, disease duration and blood pressure (p?<?0.04).

Conclusions/interpretation

Although body mass associates positively with pro- and anti-inflammatory cytokine levels, patients with type 2 diabetes have higher cytokine levels independent of the prevailing BMI. LADA and type 1 diabetes could not be distinguished by systemic cytokines.     

Role of 0.4% glyceryl trinitrate ointment after haemorrhoidectomy: results of a prospective randomised study

Introduction

Conventional haemorrhoidectomy (CH) is well known to cause significant post-operative pain and delayed return to daily activities. Both surgical wounds and sphincterial apparatus spasms are likely responsible for the pain. In this study, we evaluated the role of glyceryl trinitrate ointment (GTN) in reducing post-operative pain, ameliorating wound healing and recovery after CH.

Patients and methods

Between 01/08 and 12/11, 203 patients with symptomatic haemorrhoids were enrolled in the study and received (103 patients) or not (100 patients) 0.4 % GTN ointment for 6 weeks after surgery. Pain was assessed using a 10-cm linear visual analogue scale (VAS). Data on post-operative pain, wound secretion and bleeding, return to normal activities and complications were recorded. Data were analysed using Fisher’s exact and Mann–Whitney tests.

Results

GTN-treated group experienced significantly less pain during the first week after surgery (p?<?0.0001). This difference was more evident starting from post-operative day 4 (p?<?0.0001). A significant higher percentage of untreated patients experienced severe pain (mean VAS score?>?7) (10 % vs 31 %). There were significant differences in terms of secretion time (p?=?0.0052) and bleeding time (p?=?0.02) in favor of GTN. In addition, the duration of itching was less in the GTN group (p?=?0.0145). Patients treated with GTN were able to an early return to daily activities compared to untreated (p?<?0.0001). Fifteen GTN-treated patients (14.6 %) discontinued the application because of local discomfort and headache.

Conclusions

GTN ointment enhances significantly post-operative recovery, reducing pain in terms of duration and intensity. This effect might be secondary to a faster wound healing expressed by reduced secretion, bleeding and itching time.     

Fast-track colorectal surgery: protocol adherence influences postoperative outcomes

Purpose

This single-center prospective cohort study, conducted outside of a clinical trial, tried to identify the importance of each fast-track surgery procedure and protocol adherence level on clinical outcomes after colorectal surgery.

Methods

From a prospectively maintained database, 606 patients who underwent elective laparoscopic or open colorectal resection within a well established fast-track surgery (FT) protocol, between 2005 and 2011, were identified. Univariate and multivariate analysis were performed to assess the relationship between each FT procedure with an adherence rate <100 % and the outcome variables (length of stay—LOS, 30-day morbidity and readmission rate). Patients were divided into four adherence level groups to FT procedures—100 %, 85–95 %,70–80 %, and <65 %. Each adherence group was compared with the other groups to evaluate differences in clinical outcome variables.

Results

Group comparisons revealed that higher levels of FT protocol adherence corresponded to significantly improved LOS and morbidity rates. Readmission rates were only significantly different between the full fast-track pathway and the less implemented groups. Multivariate analyses revealed that the fast removal of bladder catheter positively influenced length of stay (p?<?0.0001) and 30-day morbidity (p?<?0.0001). Laparoscopy surgery, no drain positioning and enforced mobilization improved LOS (p?=?0.027, p?<?0.0001, p?=?0.002, respectively). Early solid feeding improved LOS (p?<?0.0001), morbidity (p?<?0.0001) and readmission rate (p?=?0.011).

Conclusion

Postoperative outcomes after colorectal surgery are directly proportional to FT protocol adherence. The early removal of the bladder catheter and early postoperative solid feeding independently influenced the length of hospital stay and 30-day morbidity rates.     

The Impact of Low Subcutaneous Fat in Patients with Nontuberculous Mycobacterial Lung Disease

Background

Nontuberculous mycobacteria (NTM) are pathogens that cause chronic respiratory disease, even in immunocompetent patients. We hypothesized that low subcutaneous fat is a predisposing factor for NTM lung disease.

Methods

Following a retrospective review of medical records from between 2005 and 2012, a total of 148 patients with NTM lung disease and 142 age- and sex-matched controls were enrolled. We evaluated subcutaneous fat using chest computed tomography (CT) scans at the midpole level of the left kidney.

Results

The median age of the patients was 62 years and 60.8 % were female. Approximately 71 % were classified into a nodular bronchiectatic group. The patient group had significantly less subcutaneous fat than the control group (39.3 vs. 53.0 cm², p = 0.001). Patients with both localized disease (43.5 vs. 53.0 cm², p = 0.042) and extensive disease (35.9 vs. 53.0 cm², p < 0.0001) had less subcutaneous fat compared with the control group. No difference in subcutaneous fat was observed with respect to the increasing bacterial load in sputum (p = 0.246). In 20 patients with prominent disease progression during the follow-up period, no significant difference was observed between subcutaneous fat at the initial diagnosis and that at the follow-up CT (36.2 vs. 42.0 cm², p = 0.47).

Conclusion

Our results suggest that lower subcutaneous fat may contribute to host susceptibility to NTM lung disease.     

Longitudinal changes in insulin sensitivity and beta cell function between women with and without a history of gestational diabetes mellitus

Aims/hypothesis

The aim of the study was to compare longitudinal changes in insulin sensitivity (S_I) and beta cell function between women with and without a history of gestational diabetes mellitus (GDM).

Methods

The prospective follow-up cohort included 235 parous non-diabetic Mexican–American women, 93 with and 142 without a history of GDM. The participants underwent dual-energy x-ray absorptiometry, OGTTs and IVGTTs at baseline and at a median of 4.1 years follow-up. The baseline values and rates of change of metabolic measures were compared between groups.

Results

At baseline, women with prior GDM (mean age 36.3 years) had similar values of S_I but higher percentages of body fat and trunk fat (p?≤?0.02), a lower acute insulin response and poorer beta cell compensation (disposition index [DI]) (p?<?0.0001) than women without GDM (mean age 37.9 years). During the follow-up, women with GDM had a faster decline in S_I (p?=?0.02) and DI (p?=?0.02) than their counterparts without GDM, with no significant differences in changes of weight or fat (p?>?0.50). Adjustment for baseline age, adiposity, calorie intake, physical activity, age at first pregnancy, additional pregnancies and changes in adiposity during follow-up increased the between-group differences in the rates of change of S_I and DI (p?≤?0.003).

Conclusions/interpretation

Mexican–American women with recent GDM had a faster deterioration in insulin sensitivity and beta cell compensation than their parous counterparts without GDM. The differences were not explained by differences in adiposity, suggesting more deleterious effects of existing fat and/or reduced beta cell robustness in women with GDM.     

The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial

Aims/hypothesis

The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes.

Methods

Children and adults (n?=?153) on CSII with HbA_1c 7.5–9.5% (58.5–80.3?mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6?months. After 4?months’ washout, participants crossed over to the other arm for 6?months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA_1c levels between arms after 6?months.

Results

Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA_1c was –0.43% (–4.74?mmol/mol) in favour of the Sensor On arm (8.04% [64.34?mmol/mol] vs 8.47% [69.08?mmol/mol]; 95% CI ?0.32%, ?0.55% [?3.50, ?6.01?mmol/mol]; p?<?0.001). Following cessation of glucose sensing, HbA_1c reverted to baseline levels. Less time was spent with sensor glucose <3.9?mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31?min/day; p?=?0.009). The mean number of daily boluses increased in the Sensor On arm (6.8?±?2.5 vs 5.8?±?1.9, p?<?0.0001), together with the frequency of use of the temporary basal rate (0.75?±?1.11 vs 0.26?±?0.47, p?<?0.0001) and manual insulin suspend (0.91?±?1.25 vs 0.70?±?0.75, p?<?0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p?=?0.40).

Conclusions/interpretation

Continuous glucose monitoring was associated with decreased HbA_1c levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.

Trial registration

ClinicalTrials.gov registration no. NCT00598663.

Funding

The study was funded by Medtronic International Trading Sarl Switzerland.     

Identifying the Risks of Anticoagulation in Patients with Substance Abuse

BACKGROUND

Warfarin is effective in preventing thromboembolic events, but concerns exist regarding its use in patients with substance abuse.

OBJECTIVE

Identify which patients with substance abuse who receive warfarin are at risk for poor outcomes.

DESIGN

Retrospective cohort study. Diagnostic codes, lab values, and other factors were examined to identify risk of adverse outcomes.

PATIENTS

Veterans AffaiRs Study to Improve Anticoagulation (VARIA) database of 103,897 patients receiving warfarin across 100 sites.

MAIN MEASURES

Outcomes included percent time in therapeutic range (TTR), a measure of anticoagulation control, and major hemorrhagic events by ICD-9 codes.

RESULTS

Nonusers had a higher mean TTR (62 %) than those abusing alcohol (53 %), drugs (50 %), or both (44 %, p?<?0.001). Among alcohol abusers, an increasing ratio of the serum hepatic transaminases aspartate aminotransferase/alanine aminotransferase (AST:ALT) correlated with inferior anticoagulation control; normal AST:ALT?≤ 1.5 predicted relatively modest decline in TTR (54 %, p?<?0.001), while elevated ratios (AST:ALT 1.50–2.0 and > 2.0) predicted progressively poorer anticoagulation control (49 % and 44 %, p?<?0.001 compared to nonusers). Age-adjusted hazard ratio for major hemorrhage was 1.93 in drug and 1.37 in alcohol abuse (p?<?0.001 compared to nonusers), and remained significant after also controlling for anticoagulation control and other bleeding risk factors (1.69 p?<?0.001 and 1.22 p?=?0.003). Among alcohol abusers, elevated AST:ALT >2.0 corresponded to more than three times the hemorrhages (HR 3.02, p?<?0.001 compared to nonusers), while a normal ratio AST:ALT ≤ 1.5 predicted a rate similar to nonusers (HR 1.19, p?<?0.05).

CONCLUSIONS

Anticoagulation control is particularly poor in patients with substance abuse. Major hemorrhages are more common in both alcohol and drug users. Among alcohol abusers, the ratio of AST/ALT holds promise for identifying those at highest risk for adverse events.     

Evaluation of pancreatic intraepithelial neoplasia and mucin expression in normal pancreata

Background/purpose

It has been suggested that pancreatic ductal adenocarcinoma (PDAC) and pancreatic intraepithelial neoplasia (PanIN) are closely related, but several reports indicate PanIN lesions can also be found in normal pancreata (normal PanINs). We examined differences in mucin expression between normal PanIN lesions and PanINs in PDACs (PDAC PanINs).

Methods

We examined 54 autopsied normal pancreata and eight autopsied PDACs for PanIN lesions; graded the pancreata specimens as PanIN-1A (non-papillary hyperplasia), PanIN-1B (papillary hyperplasia), PanIN-2 (atypical hyperplasia) or PanIN-3 (carcinoma in situ); and tested the PanIN lesions for expression of MUC1 (pan-epithelial membrane-associated mucin) and MUC5AC (gastric secretory mucin) which were both previously detected in PDACs.

Results

In normal PanIN-1A, PanIN-1B and PanIN-2 specimens, MUC1 was expressed in 2.8, 10.5 and 9.1%, respectively, compared to 19.1, 27.6 and 13.0% in PDAC PanIN-1A, PanIN-1B and PanIN-2 specimens, respectively. MUC5AC was expressed in 41.0, 65.7 and 36.4% of normal PanIN-1A, PanIN-1B and PanIN-2 specimens, respectively, and in 80.9, 75.8 and 78.3% of PDAC PanIN-1A, PanIN-1B and PanIN-2 specimens, respectively. Differences in the frequency of MUC1 expression were significant between normal and PDAC PanIN-1A (p?<?0.0001) and PanIN-1B (p?<?0.05); and differences in the frequency of MUC5AC expression were significant between normal and PDAC PanIN-1A (p?<?0.0001) and PanIN-2 (p?<?0.05).

Conclusions

Normal PanIN and PDAC PanIN lesions differed in the rates of MUC1 and MUC5AC expression.     

Alveolar Air and O2 Uptake During Exercise in Patients With Heart Failure

Background

Peak exercise pulmonary oxygen uptake (V?O₂) is a primary marker of prognosis in heart failure (HF). The pathophysiology of impaired peak V?O₂ is unclear in patients. To what extent alveolar airway function affects V?O₂ during cardiopulmonary exercise testing (CPET) has not been fully elucidated. This study aimed to describe how changes in alveolar ventilation (V?_A), volume (V_A), and related parameters couple with exercise V?O₂ in HF.

Omega-3 Polyunsaturated Fatty Acids Increase Plasma Adiponectin to Leptin Ratio in Stable Coronary Artery Disease

Background

Growing evidence suggests a cardioprotective role of omega-3 polyunsaturated fatty acids (PUFA). However, the exact mechanisms underlying the effects of omega-3 PUFA in humans have not yet been fully clarified.

Purpose

We sought to evaluate omega-3 PUFA-mediated effects on adipokines in patients with stable coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI).

Methods

We conducted a prospective, double-blind, placebo-controlled, randomized study, in which adiponectin, leptin and resistin were determined at baseline, 3–5 days and 30 days during administration of omega-3 PUFA 1 g/day (n?=?20) or placebo (n?=?28).

Results

As compared to controls administration of omega-3 PUFA resulted in increase of adiponectin by 13.4 % (P?<?0.0001), reduction of leptin by 22 % (P?<?0.0001) and increase of adiponectin to leptin (A/L) ratio by 45.5 % (P?<?0.0001) at 30 days, but not at 3–5 days. Compared with placebo adiponectin was 12.7 % higher (P?=?0.0042), leptin was 16.7 % lower (P?<?0.0001) and A/L ratio was 33.3 % higher (P?<?0.0001) in the omega-3 PUFA group at 30 days. Resistin decreased similarly in both groups after 1 month, without intergroup differences (P?=?0.32). The multivariate model showed that the independent predictors of changes in adiponectin at 1 month (P?<?0.001) were: omega-3 PUFA treatment, baseline platelet count, total cholesterol and those in leptin (P?<?0.0001) were: omega-3 PUFA treatment and waist circumference. Independent predictors of A/L ratio changes (P?<?0.0001) were: assigned treatment, current smoking and hyperlipidemia.

Conclusions

In high risk stable coronary patients after PCI omega-3 PUFA supplementation improves adipokine profile in circulating blood. This might be a novel, favourable mechanism of omega-3 PUFA action.     

Risk factors for choledocholithiasis in a south Indian population: A case–control study

Aim

To identify risk factors for common bile duct (CBD) stones in a south Indian population.

Methods

Demographic characteristics and diet details were obtained from patients with isolated CBD stones (Gp I) and those with combined CBD and gallstones (Gp II) and age- and sex-matched controls. The risk factors were compared between the two groups.

Results

The demographic characteristics were similar between the two groups and matched controls. The significant risk factors for Gp I were infrequent consumption of green vegetable (odds ratio (OR), 2.3; p?<?0.05), intake of tea/coffee (OR 3.3; p?<?0.01) and less consumption of sugar (p?<?0.01). For Gp II, the risk factors were frequent intake (>3 times per week) of spices (OR, 2.8; p?<?0.05), fried foods (OR, 2.7; p?<?0.05), tamarind (OR, 2.8; p?<?0.01), and quantum of oil (p?<?0.01) per month. Green vegetables (OR, 8.5; p?<?0.00001) and sugar (9.5?+?4.2 vs. 13.8?+?11.2 g; p?<?0.00001) were protective. Between the two groups, the risk factors for Gp II were less frequent green vegetable intake (OR: 6.4; p?<?0.00001), more frequent spicy food (0-3 times per week) (OR, 7.0; p?<?0.05), and higher monthly oil intake (251?+?105 vs. 292?+?89 mL; p?<?0.05).

Conclusion

CBD stones in both groups were associated with reduced intake of sugar and green vegetables. Our findings need to be validated in larger studies.