Cardiovascular and mortality benefits of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists as third-step glucose-lowering medicine in patients with type 2 diabetes: a retrospective cohort analysis.

INTRODUCTION: Studies have found that sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP1) have cardiovascular benefits for patients with type 2 diabetes (DM2) and atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF). The literature does not provide evidence specifically for patients with these conditions who are adding one of these medicines to two glucose-lowering medications (ie, as "third-step" therapy). We explored the effects of different third-step medications on cardiovascular outcomes in patients with diabetes and these comorbid conditions. Specifically, we compared third-step SGLT2 or GLP1 to third-step dipeptidyl peptidase-4 inhibitors (DPP4), insulin, or thiazolidinediones (TZD). RESEARCH DESIGN AND METHODS: We assembled a retrospective cohort of adults at five Kaiser Permanente sites with DM2 and ASCVD, CKD, or HF, initiating third-step treatment between 2016 and 2020. Propensity score weighted Poisson models were used to calculate adjusted rate ratios (ARRs) for all-cause mortality, incident major adverse cardiovascular event (MACE), and incident HF hospitalization in patients initiating SGLT2 or GLP1 compared with DPP4, insulin, or TZD. RESULTS: We identified 27 542 patients initiating third-step treatment with one or more of these conditions (19 958 with ASCVD, 14 577 with CKD, and 3919 with HF). ARRs for GLP1 and SGLT2 versus DPP4, insulin, and TZD in the patient subgroups ranged between 0.22 and 0.55 for all-cause mortality, 0.38 and 0.81 for MACE, and 0.46 and 1.05 for HF hospitalization. Many ARRs were statistically significant, and all significant ARRs showed a benefit (ARR <1) for GLP1 or SGLT2 when compared with DPP4, insulin, or TZD. CONCLUSIONS: Third-step SGLT2 and GLP1 are generally associated with a benefit for these outcomes in these patient groups when compared with third-step DPP4, insulin, or TZD. Our results add to evidence of a cardiovascular benefit of SGLT2 and GLP1 and could inform clinical guidelines for choosing third-step diabetes treatment.

Acute Pancreatitis with Colonic Pseudo-obstruction in a Patient with COVID-19.

Angiotensin-converting enzyme 2 receptor, the receptor used by severe acute respiratory syndrome coronavirus-2 (COVID-19) to infect cells, is found not only on respiratory epithelium but also in the small bowel, large bowel, and pancreas. There have been rare reports of acute pancreatitis (AP) in COVID-19 patients without an obvious etiology other than the underlying viral syndrome. We present a patient who was admitted with COVID-19 and developed AP and colonic pseudo-obstruction.

Common Gastrointestinal Medications Implicated in Drug-Induced Liver Injury.

Content available: Author Interview and Audio Recording.

Associations between sinus tachycardia and adverse cardiovascular outcomes and mortality in cancer patients.

BACKGROUND: Sinus tachycardia in cancer reflects a significant multi-system organ stressor and disease, with sparse literature describing its clinical significance. We assessed cardiovascular (CV) and mortality prognostic implications of sinus tachycardia in cancer patients. METHODS: We conducted a case-control study of 622 cancer patients at a U.S. urban medical center from 2008 to 2016. Cases had ECG-confirmed sinus tachycardia [heart rate (HR) ≥100 bpm] in ≥3 different clinic visits within 1 year of cancer diagnosis excluding a history of pulmonary embolism, thyroid dysfunction, left ventricular ejection fraction <50%, atrial fibrillation/flutter, HR >180 bpm. Adverse CV outcomes (ACVO) were heart failure with preserved ejection fraction (HFpEF), HF with reduced EF (HFrEF), hospital admissions for HF exacerbation (AHFE), acute coronary syndrome (ACS). Regression analyses were conducted to examine the effect of sinus tachycardia on overall ACVO and survival. RESULTS: There were 51 cases, age and sex-matched with 571 controls (mean age 70±10, 60.5% women, 76.4% Caucasian). In multivariate analysis over a 10-year follow-up period, sinus tachycardia (HR ≥100 vs. <100 bpm) was an independent predictor of overall ACVO (OR 2.8, 95% CI: 1.4-5.5; P=0.006). There was increased incidence of HFrEF (OR 3.3, 95% CI: 1.6-6.5; P=0.004) and AHFE (OR 6.3, 95% CI: 1.6-28; P=0.023), but not HFpEF or ACS (P>0.05) compared with controls. Sinus tachycardia was a significant predictor of overall mortality after adjusting for significant covariates (HR 2.9, 95% CI 1.8-5; P<0.001). CONCLUSIONS: Independent of typical factors that affect cardiovascular disease, sinus tachycardia around the time of cancer treatment is associated with increased ACVO and mortality in cancer patients at 10 years of follow-up.

Interobserver reliability of methods to determine complete resection of adenomas in colonoscopy.

BACKGROUND: Forceps margin biopsy and polypectomy specimen margins have both been used to assess for polypectomy resection adequacy. The interobserver reliability of the two methods has not been well described. METHODS: The interpretability of polypectomy specimens for presence of residual neoplasia at the margin was assessed by two blinded pathologists. Next, the concordance of forceps margin biopsy interpretations between three blinded pathologists was evaluated by calculation of interobserver κ. RESULTS: Rates of polypectomy specimen margin interpretability were low: 24/92 (26 %) for pathologist A, 28/92 (30.4 %) for pathologist B. Concordance of forceps margin biopsy interpretations (n = 129) between pathologists was high. Two internal pathologists showed substantial agreement in margin biopsy interpretations (κ 0.779; 95 %CL 0.543, 0.912). The concordance remained strong after biopsies were reviewed by a third, external pathologist (κ 0.829; 95 %CL 0.658, 0.924). There was complete agreement on 123/129 (95.3 %) between all three pathologists for presence of neoplasia. CONCLUSION: The majority of polypectomy specimen margins were uninterpretable by pathologists for presence of residual neoplasia. Forceps margin biopsy shows strong interobserver reliability in adenomatous lesions.

Colonic Polypoid Arteriovenous Malformation Causing Symptomatic Anemia.

Vascular ectasias, which can be classified as angiodysplasias and arteriovenous malformations (AVMs), accounts for approximately 3% of lower gastrointestinal bleeding. Typically, colonic AVMs are solitary, large, and flat or elevated red lesions on endoscopy. We present an interesting case of a polypoid ulcerated AVM in the transverse colon causing symptomatic anemia, which was resected endoscopically with a resolution of symptoms. Polypoid colonic AVMs are rather rare with only 15 other cases described in the literature. This case highlights the approach to endoscopic management of these lesions.

Assessing the Safety of Direct-Acting Antiviral Agents for Hepatitis C.

Importance: Recent reports based on the US Food and Drug Administration's voluntary Adverse Events Reporting System raised questions about the safety of direct-acting antivirals (DAAs) for treatment of the hepatitis C virus (HCV). Objective: To assess the rates of adverse events in patients with HCV infection exposed to DAAs compared with those not exposed. Design, Setting, and Participants: A retrospective cohort study calculated unadjusted adverse event rates for exposed vs unexposed time, using claims and clinical data from 3 health systems between January 1, 2012, and December 31, 2017. Of 82 419 eligible adults, a total of 33 808 who met eligibility criteria (age, 18-88 years; HCV quantitative result or genotype from 2012 or later; continuously enrolled; naive to DAA treatment at baseline) were included. Marginal structural modeling methods were used to adjust time-to-event analyses for characteristics that are associated with both outcomes and probability of treatment. Interventions or Exposures: Exposure to DAAs compared with no DAA exposure. Main Outcomes and Measures: Death, multiple organ failure, liver cancer, hepatic decompensation, acute-on-chronic liver event, acute myocardial infarction, ischemic or hemorrhagic stroke, arrhythmia, acute kidney failure, nonliver cancer, hepatitis B reactivation, hospitalizations, and emergency department visits. Results: Of the 33 808 patients who met all inclusion criteria, 20 899 (61.8%) were men; mean (SD) age was 57.2 (10.6) years. In unadjusted analyses, DAA exposure was associated with significantly lower rates of death (10.7 vs 33.7 events per 1000 person-years; rate ratio [RR], 0.32, 95% CI, 0.25-0.40). Seven other unadjusted adverse clinical events ratios were below 70% and statistically significant favoring the DAA group: multiple organ failure (RR, 0.56; 95% CI, 0.44-0.72), liver cancer (RR, 0.62; 95% CI, 0.48-0.80), hepatic decompensation (RR, 0.62; 95% CI, 0.52-0.73), acute-on-chronic liver event (RR, 0.68; 95% CI, 0.56-0.84), acute myocardial infarction (RR, 0.64; 95% CI, 0.42-0.97), ischemic stroke (RR, 0.63; 95% CI, 0.42-0.95), and hemorrhagic stroke (RR, 0.47; 95% CI, 0.25-0.89); none favored the non-DAA group. In the marginal structural modeling-adjusted analysis, DAA exposure was associated with statistically significant lower odds of adverse events than non-DAA exposure for death (adjusted odds ratio [aOR], 0.42; 95% CI, 0.30-0.59), multiple organ failure (aOR, 0.67; 95% CI, 0.49-0.90), hepatic decompensation (aOR, 0.61; 95% CI, 0.49-0.76), acute-on-chronic liver event (aOR, 0.71; 95% CI, 0.56-0.91), and arrhythmia (aOR, 0.47; 95% CI, 0.25-0.88). Conclusions and Relevance: Direct-acting antiviral exposure may not be associated with higher rates of any serious adverse events, including those related to liver, kidney, and cardiovascular systems. Safety concerns based on previous reports did not appear to be supported in this study with more comprehensive data and rigorous statistical methods.

Alternative approaches to polyp extraction in colonoscopy: a proof of principle study.

BACKGROUND AND AIMS: A limitation of determination of the completeness of resection in polypectomy is polyp fragmentation. When a polyp fragments, the pathologist cannot determine resection completeness. Alternative approaches to reduce polyp fragmentation include reducing shearing forces on the polyp or removing polyps through the instrument channel. The primary aim of this study was to assess fragmentation of polyps extracted using different approaches from conventional polyp retrieval. METHODS: Polyps (5-15 mm) resected by cold snare or cautery by 3 colonoscopists were extracted from the colonoscope using 1 of 4 techniques. Method I was the conventional method of pressing the suction valve button and retrieving the polyp through a trap. Method II involved removing the suction valve, covering the open suction valve cylinder with a finger. Method III used a Roth Net polyp retriever placed through the instrument channel. Method IV involved connecting a polyp trap to suction onto the instrument channel port. Fragmentation was defined as multiple pieces of the specimen in formalin, as grossly described by the pathologist. Alternative approaches (methods II, III, and IV) were all compared with the conventional method (method I). RESULTS: The method I fragmentation rate of polyps was 60.3% (123/204). Method II extraction reduced fragmentation to 43.0% (52/121, P = .003), proving that fragmentation occurs with passage through the suction valve channel. Method III had a lower fragmentation rate of 23.1% (6/26, P < .001). Method IV likewise showed a reduced fragmentation rate of 18.5% (5/27, P < .001). CONCLUSIONS: Polyp fragmentation is reduced by removal of the suction valve button. There is also a decrease in fragmentation rates in removing the polyp by connecting the polyp trap to the instrument port. Our study suggests that decreasing polyp fragmentation and improving pathology margin interpretability is possible through methods that extract polyps through the instrument port with currently available devices.

Risk of Hepatitis B Virus Reactivation Among Patients Treated With Ledipasvir-Sofosbuvir for Hepatitis C Virus Infection.

BACKGROUND: Direct acting antiviral (DAA) agents are the standard of care for treatment of hepatitis C virus (HCV)-infected individuals. Hepatitis B virus (HBV) reactivation during HCV treatment has been reported, the incidence and clinical outcome remains unclear. The aim of our study is to examine the risk of HBV reactivation in actively infected or previously exposed patients during or after HCV treatment with DAAs. METHODS: Adults with chronic HCV infection previously exposed or actively infected with HBV and treated with DAAs between December 2015 to 2016 were included. Electronic medical records were reviewed for HCV treatment dates, HCV treatment response, DAA used, HBV status, and concurrent HBV treatment. Primary end-point was to determine the risk of HBV reactivation during or up to 3 months after DAA treatment. RESULTS: We identified 283 patients, and 100% of patients completed HCV treatment with ledipasvir-sofosbuvir. 93% had HCV genotype-1 of whom 91% achieved sustained viral response at 12 weeks posttreatment (SVR-12). In total, 7% had HCV genotype-4 who achieved SVR-12 of 84%. Mean (±SD) age was 59.7 (±7) years, and 58% were male. A total of 45% of patients had hepatitis B core antibody (HBcAb) positive and hepatitis B surface antigen (HBsAg) negative. In total, 55% of patients had a positive HBsAg before HCV DAA treatment. No HBV reactivation was encountered in the (HBcAb) positive HBsAg-negative cohort nor in the (HBsAg) positive group with 95% confidence interval (0-0.023) and (0-0.019), respectively. CONCLUSION: In our study of patients with HCV and isolated hepatitis B core or HBsAg positivity, no HCV patients treated with DAA experienced HBV reactivation.

Outcomes for concomitant common iliac artery aneurysms after endovascular abdominal aortic aneurysm repair.

OBJECTIVE: This study evaluated the morbidity of endovascular abdominal aortic aneurysm repair (EVAR) in patients with concomitant common iliac artery aneurysm (CCIAA). METHODS: This was a retrospective review of all patients who underwent elective EVAR from June 2006 through June 2012 at a single institution. Demographics, comorbidities, preoperative presentation, intraoperative details, and postoperative complications were tabulated. Patients with CCIAA were categorized into three groups according to the distal extent of their iliac limb: iliac limb extension into the external iliac artery with internal iliac artery coil embolization (EE); flared iliac limb ≥20 mm in diameter to the iliac bifurcation (FL); and iliac limb ≤20 mm ending proximal to the CCIAA (no-FL). RESULTS: During this period, 627 consecutive patients underwent elective EVAR and preoperative computed tomographic angiograms were available for 523 patients to evaluate the presence of CCIAA. Of these, 211 patients (40.2%) had a CCIAA in at least one common iliac artery, with a total of 307 aneurysmal arteries. Of these 307 aneurysmal arteries, 62 (20.2%) were treated with EE, 132 (43.0%) were treated with FL, and 113 (36.8%) had a sufficient landing zone in the proximal common iliac artery to use an iliac limb ≤20 mm in diameter (no-FL). The overall reintervention rate was 12.4% of patients, with a higher reintervention rate between patients with CCIAA compared with those without (15.2% vs 10.9%; P = .039). There were no significant differences in reintervention rates between the EE, FL, and no-FL techniques (4.5% vs 4.8% vs 6.2%; P = .802) over a mean 59.8 months follow-up. The FL and EE techniques had a lower risk of distal endoleak than the no-FL technique, but the difference was not statistically significant (3.2% vs 2.3% vs 5.3% compared with 4.23% in the entire cohort). CONCLUSIONS: Patients with CCIAA had a higher reintervention rate after EVAR for abdominal aortic aneurysm compared with non-CCIAA patients. Of the techniques studied (EE, FL, and no-FL), there was no significant difference in reintervention rates between the three. All three techniques remain viable options for the endovascular repair of CCIAA.

Pulmonary Hypertension in a Patient With Congenital Heart Defects and Heterotaxy Syndrome.

BACKGROUND: Heterotaxy syndrome, also called isomerism, is a condition in which abdominal and thoracic organs are located in abnormal body positions. Pulmonary hypertension (PHTN) is an uncommon clinical feature of heterotaxy syndrome. CASE REPORT: We describe the case of a 26-year-old male who developed PHTN as a rare manifestation of heterotaxy syndrome. To our knowledge, PHTN has never been reported as a prominent clinical feature in a patient with heterotaxy syndome and congenital cardiac abnormalities. CONCLUSION: It is important for the clinician to be aware of potentially serious consequences of PHTN in the setting of heterotaxy syndrome.

Tissue Plasminogen Activator Use in Cardiac Arrest Secondary to Fulminant Pulmonary Embolism.

BACKGROUND: Tissue plasminogen activator (tPA) is used emergently to dissolve thrombi in the treatment of fulminant pulmonary embolism. Currently, there is a relative contraindication to tPA in the setting of traumatic or prolonged cardiopulmonary resuscitation > 10 minutes because of the risk of massive hemorrhage. METHODS: Our single-center, retrospective study investigated patients experiencing cardiac arrest (CA) secondary to pulmonary embolus. We compared the effectiveness of advanced cardiac life support with the administration of tPA vs. the standard of care consisting of advanced cardiac life support without thrombolysis. The primary endpoint was survival to discharge. Secondary endpoints were return of spontaneous circulation (ROSC), major bleeding, and minor bleeding. RESULTS: We analyzed 42 patients, of whom 19 received tPA during CA. Patients who received tPA were not associated with a statistically significant increase in survival to discharge (10.5% vs. 8.7%, P = 1.00) or ROSC (47.4% vs. 47.8%, P = 0.98) compared to the control group. We observed no statistically significant difference between the groups in major bleeding events (5.3% in the tPA group vs. 4.3% in the control group, P = 1.00) and minor bleeding events (10.5% in the tPA group vs. 0.0% in the control group, P = 0.11). CONCLUSION: This study did not find a statistically significant difference in survival to discharge or in ROSC in patients treated with tPA during CA compared to patients treated with standard therapy. However, because no significant difference was found in major or minor bleeding, we suggest that the potential therapeutic benefits of this medication should not be limited by the potential for massive hemorrhage. Larger prospective studies are warranted to define the efficacy and safety profile of thrombolytic use in this population.

In Search for Equilibrium: Immunosuppression Versus Opportunistic Infection.

Post-transplant immunosuppression is necessary to prevent organ rejection. Immunosuppression itself can introduce complications arising from opportunistic infections. We present a case of disseminated blastomycosis manifested only as a skin lesion in an asymptomatic patient post-orthotopic heart transplantation. A 64-year-old female who had recently undergone orthotopic heart transplant for end-stage ischemic cardiomyopathy presented for a scheduled routine cardiac biopsy. The patient had no current complaints other than a crusted plaque noticed at her nasal tip. It initially manifested 6 months after surgery as a pimple that she repeatedly tried to manipulate resulting in redness and crust formation. Her immunosuppressive and prophylactic medications included: mycophenolate, tacrolimus, prednisone, bactrim, acyclovir, valganciclovir, pyrimethamine/sulfadiazine, and fluconazole. On physical examination, she was flushed, with a large and exquisitely tender crusted necrotic lesion involving almost the entire half of the nose anteriorly, the left forehead and right side of the neck. She had decreased air entry over the right lung field as well. A computed tomography (CT) image of the chest was ordered to investigate this concerning physical exam finding in the post-transplant state of this patient on immunosuppressive therapy. Chest CT revealed bilateral nodular pulmonary infiltrates with confluence in the posterior right upper lobe. Blood cultures for aerobic and anerobic organisms were negative. Both excisional biopsy of the nasal cutaneous ulcer and bronchial biopsy demonstrated numerous fungal yeast forms morphologically consistent with Blastomyces. Cultures of both specimens grew Blastomyces dermatitidis, with methicillin-resistant Staphylococcus aureus (MRSA) superinfection of the nose. She received 14 days of intravenous (IV) amphotericin B for disseminated blastomycosis and 7 days of IV vancomycin for MRSA. Her symptoms and cutaneous lesions improved and she received maintenance itraconazole treatment for 1 year. This case illustrates a delicate balance that must be struck between suppressing the immune response to prevent graft rejection and avoiding over-immunosuppression that can lead to susceptibility to infection. Thus, in any post-transplant patient, a vigorous history and physical must be performed given that infections may present without symptoms and cause grave consequences.

Management of Atrio-Esophageal Fistula Following Left Atrial Ablation.

Currently, no guidelines have been established for the treatment of atrio-esophageal fistula (AEF) secondary to left atrial ablation therapy. After comprehensive literature review, we aim to make suggestions on the management of this complex complication and also present a case series. We performed a review of the existing literature on AEF in the setting of atrial ablation. Using keywords atrial fibrillation, atrial ablation, fistula formation, atrio-esophageal fistula, complications, interventions, and prognosis, a search was made using the medical databases PUBMED and MEDLINE for reports in English from 2000 to April 2015. A statistical analysis was performed to compare the three different intervention arms: medical management, stent placement and surgical intervention. The results of our systematic review confirm the high mortality rate associated with AEF following left atrial ablation and the necessity to diagnose atrio-esophageal injury in a timely manner. The mortality rates of this complication are 96% with medical management alone, 100% with stent placement, and 33 % with surgical intervention. Atrio-esophageal injury and subsequent AEF is an infrequent but potentially fatal complication of atrial ablation. Early, prompt, and definitive surgical intervention is the treatment of choice.

A Rare Case of Cardiac Tamponade Induced by Chronic Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease primarily involving the joint synovium. RA is a systemic disease which has many known extra-articular manifestations. We present a unique case of a patient with long standing RA who presented with a primary complaint of chest and back pain. Echocardiography revealed borderline normal left ventricular function and a large pericardial effusion with the finding of elevated intrapericardial pressure suspicious for cardiac tamponade. Infectious workup was all found to be negative. The presence and elevation of anti-cyclic citrullinated peptide antibody, rheumatoid factor and C-reactive protein (CRP) confirmed the patient was having an active flare-up of RA. It was determined that this flare-up was the cause of the cardiac tamponade. A pericardiocentesis was performed and 850 mL of bloody fluid was drained. The patient remained stable following the pericardiocentesis. At his follow-up visit, repeat echocardiogram showed no signs for pericardial effusion. Although there has been extensive study of RA, there are only a few documented cases noting the occurrence of cardiac tamponade in these patients. Therefore, it is important for the clinician to be aware of and recognize this potentially serious cardiac outcome associated with a common rheumatologic condition.

Correlation Between Partial Pressure of Arterial Carbon Dioxide and End Tidal Carbon Dioxide in Patients with Severe Alcohol Withdrawal.

BACKGROUND: Respiratory depression is a common adverse effect of benzodiazepine administration to patients with severe alcoholic withdrawal. This study was conducted to assess the value of end tidal carbon dioxide (ETCO2) levels compared to partial pressure of arterial carbon dioxide (PaCO2) levels in monitoring respiratory depression secondary to benzodiazepine treatment in patients with severe alcohol withdrawal. METHODS: We retrospectively analyzed 36 patients admitted to the intensive care unit for severe alcohol withdrawal who had been administered sedative agents. RESULTS: We observed a statistically significant correlation between PaCO2 and ETCO2 at time 1 (r=0.74, P<0.01) and time 3 (r=0.52, P=0.02) but not at time 2 (r=0.22, P=0.31). CONCLUSION: Our study confirms a positive correlation between PaCO2 and ETCO2 levels in patients experiencing severe alcohol withdrawal.

PSI:Biology-materials repository: a biologist's resource for protein expression plasmids.

The Protein Structure Initiative:Biology-Materials Repository (PSI:Biology-MR; MR; http://psimr.asu.edu ) sequence-verifies, annotates, stores, and distributes the protein expression plasmids and vectors created by the Protein Structure Initiative (PSI). The MR has developed an informatics and sample processing pipeline that manages this process for thousands of samples per month from nearly a dozen PSI centers. DNASU ( http://dnasu.asu.edu ), a freely searchable database, stores the plasmid annotations, which include the full-length sequence, vector information, and associated publications for over 130,000 plasmids created by our laboratory, by the PSI and other consortia, and by individual laboratories for distribution to researchers worldwide. Each plasmid links to external resources, including the PSI Structural Biology Knowledgebase ( http://sbkb.org ), which facilitates cross-referencing of a particular plasmid to additional protein annotations and experimental data. To expedite and simplify plasmid requests, the MR uses an expedited material transfer agreement (EP-MTA) network, where researchers from network institutions can order and receive PSI plasmids without institutional delays. As of March 2011, over 39,000 protein expression plasmids and 78 empty vectors from the PSI are available upon request from DNASU. Overall, the MR's repository of expression-ready plasmids, its automated pipeline, and the rapid process for receiving and distributing these plasmids more effectively allows the research community to dissect the biological function of proteins whose structures have been studied by the PSI.

Protein Structure Initiative Material Repository: an open shared public resource of structural genomics plasmids for the biological community.

The Protein Structure Initiative Material Repository (PSI-MR; http://psimr.asu.edu) provides centralized storage and distribution for the protein expression plasmids created by PSI researchers. These plasmids are a resource that allows the research community to dissect the biological function of proteins whose structures have been identified by the PSI. The plasmid annotation, which includes the full length sequence, vector information and associated publications, is stored in a freely available, searchable database called DNASU (http://dnasu.asu.edu). Each PSI plasmid is also linked to a variety of additional resources, which facilitates cross-referencing of a particular plasmid to protein annotations and experimental data. Plasmid samples can be requested directly through the website. We have also developed a novel strategy to avoid the most common concern encountered when distributing plasmids namely, the complexity of material transfer agreement (MTA) processing and the resulting delays this causes. The Expedited Process MTA, in which we created a network of institutions that agree to the terms of transfer in advance of a material request, eliminates these delays. Our hope is that by creating a repository of expression-ready plasmids and expediting the process for receiving these plasmids, we will help accelerate the accessibility and pace of scientific discovery.