The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Pathogenesis and outcomes of traumatic injuries of the esophagus

Traumatic injury of the esophagus is extremely uncommon. The aims of this study were to use the Pennsylvania Trauma Outcome Study (PTOS) database to identify clinical factors predictive of esophageal trauma, and to report the morbidity and mortality of this injury. A cross‐sectional review of patients presenting to 20 Level I trauma centers in Pennsylvania from 2004 to 2010 was performed. We compared clinical and demographic variables between patients with and without esophageal trauma both prior to and after arrival in the emergency room (ER). Primary mechanism of injury and clinical outcomes were analyzed. There were 231 694 patients and 327 (0.14%) had esophageal trauma. Patients with esophageal trauma were considerably younger than those without this injury. The risk of esophageal trauma was markedly increased in males (odds ratio [OR] = 2.62 [CI 1.98–3.47]). The risk was also increased in African Americans (OR = 4.61 [CI 3.65–5.82]). Most cases were from penetrating gunshot and stab wounds. Only 34 (10.4%) of esophageal trauma patients underwent an upper endoscopy; diagnosis was usually made by CT, surgery, or autopsy. Esophageal trauma patients were more likely to require surgery (35.8% vs. 12.5%; P < 0.001). Patients with esophageal trauma had a substantially higher mortality than those without the injury (20.5% vs. 1.4%; P < 0.005). In logistic regression modeling, traumatic injury of the esophagus (OR = 3.43 [2.50–4.71]) and male gender (OR = 1.52 [1.46–1.59]) were independently associated with mortality. For those patients with esophageal trauma, there was an association between trauma severity and mortality (OR = 1.10 [1.07–1.12]) but not for undergoing surgery within the first 24 hours of hospitalization (OR = 0.84; 0.39–1.83). Our study on traumatic injury of the esophagus is in concordance with previous studies demonstrating that this injury is rare but carries considerable morbidity (～46%) and mortality (～20%). The injury has a higher morbidity and mortality when the thoracic esophagus is involved compared to the cervical esophagus alone. The injury most commonly occurs in younger, Black males suffering gunshot wounds. Efforts to control gun violence in Pennsylvania are of paramount importance.     

Colonoscopy Preparation: Polyethylene Glycol with Gatorade Is as Safe and Efficacious as Four Liters of Polyethylene Glycol with Balanced Electrolytes

Background

Four liters of polyethylene glycol 3350 (PEG) with balanced electrolytes for colonoscopy preparation has had poor acceptance. Another approach is the use of electrolyte-free PEG combined with 1.9?L of Gatorade. Despite its widespread use, there are no data on metabolic safety and minimal data on efficacy. Our aim was to assess the efficacy and electrolyte safety of these two PEG-based preparations.

Methods

This was a prospective, randomized, single-blind, non-inferiority trial. Patients were randomized to 238?g PEG?+?1.9?L Gatorade or 4?L of PEG-ELS containing 236?g PEG. Split dosing was not performed. On procedure day blood was drawn for basic chemistries. The primary outcome was preparation quality from procedure photos using the Boston Bowel Preparation Scale.

Results

We randomized 136 patients (66 PEG?+?Gatorade, 70 PEG-ELS). There were no differences in preparation scores between the two agents in the ITT analysis (7.2?±?1.9 for PEG-ELS and 7.0?±?2.1 for PEG?+?Gatorade; p?=?0.45). BBPS scores were identical for those who completed the preparation and dietary instructions as directed (7.4?±?1.7 for PEG-ELS, and 7.4?±?1.8 for PEG?+?Gatorade; p?=?0.98). There were no statistical differences in serum electrolytes between the two preparations. Patients who received PEG?+?Gatorade gave higher overall satisfaction scores for the preparation experience (p?=?0.001), and had fewer adverse effects.

Conclusions

Use of 238?g PEG?+?1.9?L Gatorade appears to be safe, better tolerated, and non-inferior to 4?L PEG-ELS. This preparation may be especially useful for patients who previously tolerated PEG-ELS poorly.     

Abdominal computed tomography prolongs length of stay and is frequently unnecessary in the evaluation of acute pancreatitis

BACKGROUND: Computed tomography (CT) can play a vital role in the diagnosis and staging of patients with acute pancreatitis. However, according to current guidelines, a CT examination should not be performed in all patients. We assessed the use of CT scanning in the evaluation of patients with acute pancreatitis at an urban teaching hospital. METHODS: Retrospective review of patients admitted with the diagnosis of acute pancreatitis from October 1999 to October 2001. We recorded demographics, laboratory values, severity of illness, length of stay, indication for CT, ordering physician, and outcome. RESULTS: Overall, 108 patients met our inclusion criteria. Of these, 58 (54%) underwent CT examination. There was no difference (all P > 0.60) in markers of severity of illness in patients undergoing CT versus no CT. The only significant difference was length of stay (P = 0.003). Patients not undergoing CT were discharged a mean of 3 days sooner. Most appropriate CTs were ordered by the gastroenterology consultants as opposed to the emergency room and medical groups; however, this group's length of stay was longest (P = 0.035). CONCLUSIONS: In 1 teaching institution, physicians ordering CT for the evaluation of acute pancreatitis frequently do so without regard to the severity of patient illness. These examinations may prolong the length of hospitalization. Continued refinement and dissemination of guidelines for the diagnostic evaluation of acute pancreatitis is needed.