Possible role of MDR1 two-locus genotypes for young-age onset ulcerative colitis but not Crohn’s disease

Background The role of the single nucleotide polymorphisms (SNPs) on positions 2677G>T/A and 3435C>T of the multi-drug-resistance gene 1 (MDR1) in inflammatory bowel disease (IBD) remains unclear. Aims To further elucidate the potential impact of MDR1 two-locus genotypes on susceptibility to IBD and disease behaviour. Patients and methods Three hundred eighty-eight German IBD patients [244 with Crohn’s disease (CD), 144 with ulcerative colitis (UC)] and 1,005 German healthy controls were genotyped for the two MDR1 SNPs on positions 2677G>T/A and 3435C>T. Genotype–phenotype analysis was performed with respect to disease susceptibility stratified by age at diagnosis as well as disease localisation and behaviour. Results Genotype distribution did not differ between all UC or CD patients and controls. Between UC and CD patients, however, we observed a trend of different distribution of the combined genotypes derived from SNPs 2677 and 3435 (χ² = 15.997, df = 8, p = 0.054). In subgroup analysis, genotype frequencies between UC patients with early onset of disease and controls showed significant difference for combined positions 2677 and 3435 (χ² = 16.054, df = 8, p = 0.034 for age at diagnosis ≥25, lower quartile). Herein the rare genotype 2677GG/3435TT was more frequently observed (odds ratio = 7.0, 95% confidence interval 2.5 – 19.7). In this group severe course of disease behaviour depended on the combined MDR1 SNPs (χ² = 16.101, df = 6, p = 0.017 for age at diagnosis ≥25). No association of MDR1 genotypes with disease subgroups in CD was observed. Conclusions While overall genotype distribution did not differ, combined MDR1 genotypes derived from positions 2677 and 3435 are possibly associated with young age onset of UC and severe course of disease in this patient group.     

Duodenal- jejunal bypass sleeve: a totally endoscopic device for the treatment of morbid obesity

Morbid obesity affects over 15 million people in the United States. Nonsurgical management produces sustained weight loss in less than 5% of patients. Despite associated comorbidities, less than 1% of obese patients seek surgical intervention. Less invasive procedures have been developed with varying success. The Endobarrier( trade mark) (GI Dynamics(trade mark), Watertown, MA) duodenal-jejunal bypass sleeve is a totally endoscopically delivered device designed to produce weight loss in the morbidly obese. We describe the first placement of a duodenal-jejunal bypass sleeve in a patient in the United States. A blinded, randomized, prospective clinical trial was approved by the Food and Drug Administration to evaluate safety and efficacy of a novel device for weight loss in the obese. The first patient enrolled was a 36-year-old woman with body mass index of 45.2. After informed consent, endoscopic placement of the device under general anesthesia was performed using fluoroscopy to confirm positioning. The device was placed without complications. At conclusion of the 3-month study period, the device was removed endoscopically. Total weight lost by the patient was 9.09 kg. Described herein is the first deployment of the duodenal-jejunal bypass sleeve in North America. The device is delivered in a totally endoscopic manner in morbidly obese patients. In our patient, total weight loss at 3 months was 9.09 kg. Continued follow-up and enrollment is ongoing to demonstrate patient safety and efficacy. Additional studies are being performed to elucidate mechanism of weight loss and future clinical applications of this device.     

Consolidating human disease learning in the Dental Emergency Clinic

Introduction

Dental undergraduates typically learn and are assessed on aspects of human disease (HD) in the early part of their programme, but it is not until later in the programme that their HD knowledge is put into practice when they provide courses of treatment for numerous patients over multiple visits. The teaching of HD provides core knowledge on medical conditions and medications and is therefore essential in allowing newly graduated dentists to provide safe treatment for medically compromised patients or those taking medications. We wanted to examine the medical complexity of patients attending a university hospital dental emergency clinic to determine whether this was a suitable group that would help students to consolidate their HD learning in the context of a single visit where treatment was also provided.

Materials and Methods

We examined the medical history of 200 patients attending the dental emergency clinic in the University Dental Hospital, Cardiff, using a previous study as a benchmark. Anonymous data were collected using the medical history proforma, and included age, gender, medications, types and number of medical conditions/disorders.

Results

Patients attending the clinic were more medically complex than those in the comparator study and the demographics reflect wider population data showing increasing numbers of older patients with greater medical morbidity.

Discussion/Conclusions

The emergency dental clinic is the place where most patients are new to the hospital, have a dental history, medical history, investigations, diagnosis and treatment in a single visit, and offers excellent opportunities for consolidating HD learning in a one-stop clinical treatment episode, guided by suitable instructors.     

Reduction of postprandial glycemic excursions in patients with type 1 diabetes: a novel human insulin formulation versus a rapid-acting insulin analog and regular human insulin

Background:

Evaluation of postprandial glycemic excursions in patients with type 1 diabetes with three prandial insulins: VIAject™ (Linjeta™), an ultra-fast insulin (UFI); insulin lispro (LIS); and regular human insulin (RHI).

Methods:

After stabilization of preprandial glycemia, 18 patients received a subcutaneous injection with an individualized insulin dose prior to a meal.

Results:

Injection of UFI resulted in a more rapid insulin absorption than with either LIS or RHI (time to half-maximal insulin levels: 13.1 ± 5.2 vs 25.4 ± 7.6 and 38.4 ± 19.5 min; p = .001 vs LIS and p < .001 vs RHI, LIS vs. RHI p < .001). Maximal postprandial glycemia was lower with UFI (0–180 min; 157 ± 30 mg/dl; p = .002 vs RHI) and LIS (170 ± 42 mg/dl; p = .668 vs RHI) than after RHI (191 ± 46 mg/dl; RHI vs LIS p = .008). The difference between maximum and minimum glycemia was smaller with UFI (70 ± 17 mg/dl) than with either RHI (91 ± 33 mg/dl; p = .007 vs UFI) or LIS (89 ± 18 mg/dl; p = .011 vs UFI). Also, the area under the blood glucose profile was lower with UFI than with RHI (0–180 min; 21.8 ± 5.8 vs 28.4 ± 7.6 g·min/dl; p < .001).

Conclusions:

The rapid absorption of UFI results in a reduction of postprandial glycemic excursions.     

Initial assessment on the impact of crystalloids versus colloids during damage control resuscitation

Background

High ratios of fresh frozen plasma:packed red blood cells in damage control resuscitation (DCR) are associated with increased survival. The impact of volume and type of resuscitative fluid used during high ratio transfusion has not been analyzed. We hypothesize a difference in outcomes based on the type and quantity of resuscitative fluid used in patients that received high ratio DCR.

Methods

A matched case control study of patients who received transfusions of ≥ four units of PRBC during damage control surgery over 4 1/2 y, was conducted at a Level I Trauma Center. All patients received a high ratio DCR, >1:2 of fresh frozen plasma:packed red blood cells. Demographics and outcomes of the type and quantity of resuscitative fluids used in combination with high ratio DCR were compared and analyzed. A Kaplan-Meier survival analysis was computed among four groups: colloid (median quantity = 1.0 L), <3 L crystalloid, 3–6 L crystalloid, and >6 L crystalloid.

Results

There were 56 patients included in the analysis (28 in the crystalloid group and 28 in the colloid group). Demographics were statistically similar. Intraoperative median units of PRBC: crystalloid versus colloid groups was 13 (IQR 8-21) versus 16 (IQR 12–19), P = 0.135; median units of FFP: 12 (IQR 7–18) versus 12 (IQR 10–18), P = 0.440. OR for 10-d mortality in the crystalloid group was 8.41 [95% CI 1.65–42.76 (P = 0.01)]. Kaplan-Meier survival analysis demonstrated lowest mortality in the colloid group and higher mortality with increasing amounts of crystalloid (P = 0.029).

Conclusions

During high ratio DCR, resuscitation with higher volumes of crystalloids was associated with an overall decreased survival, whereas low volumes of colloid use were associated with increased survival. In order to improve outcomes without diluting the survival benefit of hemostatic resuscitation, guidelines should focus on effective low volume resuscitation when high ratio DCR is used. A multi-institutional analysis is needed in order to validate these results.     

Adjuvant Peptide Pulsed Dendritic Cell Vaccination in Addition to T Cell Adoptive Immunotherapy for Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Adoptive cellular immunotherapy has been shown to be effective in the management of cytomegalovirus (CMV) reactivation and disease. Whether adjuvant dendritic cell (DC) vaccination will provide additional benefit in prophylaxis or treatment of CMV in hematoietic cell transplantation (HSCT) recipients is unknown. In this study, we administered prophylactic CMV-peptide specific T cell infusions, followed by 2 doses of intradermal CMV peptide-pulsed DC vaccine, to 4 HSCT recipients. There were no immediate adverse events associated with T cell infusion or DC vaccinations. One of the 4 patients developed grade III acute gut graft-versus-host disease. Immune reconstitution against CMV was detected in all 4 patients. Patients receiving CMV peptide-specific T cells and DC vaccination had peak immune reconstitution at least 10 days after the second DC vaccination. In summary, combining DC vaccine with T cell infusion appears feasible, although further study is required to ascertain its safety and efficacy in augmenting the effects of infusing donor-derived CMV-specific T cells.