BackgroundRegulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown. MethodsWe randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio. ResultsAt baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 10...

/pdf/semaglutide-and-cardiovascular-outcomes-in-patients-with-48r32ka2fm.pdf

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

Background and objective The Atlanta classification of acute pancreatitis enabled standardised reporting of research and aided communication between clinicians. Deficiencies identified and improved understanding of the disease make a revision necessary. Methods A web-based consultation was undertaken in 2007 to ensure wide participation of pancreatologists. After an initial meeting, the Working Group sent a draft document to 11 national and international pancreatic associations. This working draft was forwarded to all members. Revisions were made in response to comments, and the web-based consultation was repeated three times. The final consensus was reviewed, and only statements based on published evidence were retained. Results The revised classification of acute pancreatitis identified two phases of the disease: early and late. Severity is classified as mild, moderate or severe. Mild acute pancreatitis, the most common form, has no organ failure, local or systemic complications and usually resolves in the first week. Moderately severe acute pancreatitis is defined by the presence of transient organ failure, local complications or exacerbation of co-morbid disease. Severe acute pancreatitis is defined by persistent organ failure, that is, organ failure >48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected). We present a standardised template for reporting CT images. Conclusions This international, web-based consensus provides clear definitions to classify acute pancreatitis using easily identified clinical and radiologic criteria. The wide consultation among pancreatologists to reach this consensus should encourage widespread adoption.

/pdf/classification-of-acute-pancreatitis-2012-revision-of-the-608d2rjeud.pdf

Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus

This document represents the first collaboration between 2 organizations-the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine-to describe best practices in nutrition therapy in critically ill children. The target of these guidelines is intended to be the pediatric critically ill patient (>1 month and 2-3 days in a PICU admitting medical, surgical, and cardiac patients. In total, 2032 citations were scanned for relevance. The PubMed/MEDLINE search resulted in 960 citations for clinical trials and 925 citations for cohort studies. The EMBASE search for clinical trials culled 1661 citations. In total, the search for clinical trials yielded 1107 citations, whereas the cohort search yielded 925. After careful review, 16 randomized controlled trials and 37 cohort studies appeared to answer 1 of the 8 preidentified question groups for this guideline. We used the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluation) to adjust the evidence grade based on assessment of the quality of study design and execution. These guidelines are not intended for neonates or adult patients. The guidelines reiterate the importance of nutrition assessment-particularly, the detection of malnourished patients who are most vulnerable and therefore may benefit from timely intervention. There is a need for renewed focus on accurate estimation of energy needs and attention to optimizing protein intake. Indirect calorimetry, where feasible, and cautious use of estimating equations and increased surveillance for unintended caloric underfeeding and overfeeding are recommended. Optimal protein intake and its correlation with clinical outcomes are areas of great interest. The optimal route and timing of nutrient delivery are areas of intense debate and investigations. Enteral nutrition remains the preferred route for nutrient delivery. Several strategies to optimize enteral nutrition during critical illness have emerged. The role of supplemental parenteral nutrition has been highlighted, and a delayed approach appears to be beneficial. Immunonutrition cannot be currently recommended. Overall, the pediatric critical care population is heterogeneous, and a nuanced approach to individualizing nutrition support with the aim of improving clinical outcomes is necessary.

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.)

Practice guidelines in acute pancreatitis.

A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism. The mission of SCCM is to secure the highest quality care for all critically ill and injured patients. Guideline Limitations: These A.S.P.E.N.−SCCM Clinical Guidelines are based on general conclusions of health professionals who, in developing such guidelines, have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy. However, practice guidelines are not intended as absolute requirements. The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival. The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines. The guidelines offer basic recommendations that are supported by review and analysis of the current literature, other national and international guidelines, and a blend of expert opinion and clinical practicality. The population of critically ill patients in an intensive care unit (ICU) is not homogeneous. Many of the studies on which the guidelines are based are limited by sample size, patient heterogeneity, variability in disease severity, lack of baseline nutritional status, and insufficient statistical power for analysis. Periodic Guideline Review and Update: This particular report is an update and expansion of guidelines published by A.S.P.E.N. and SCCM in 2009 (1). Governing bodies of both A.S.P.E.N. and SCCM have mandated that these guidelines be updated every three to five years. The database of randomized controlled trials (RCTs) that served as the platform for the analysis of the literature was assembled in a joint “harmonization process” with the Canadian Clinical Guidelines group. Once completed, each group operated separately in their interpretation of the studies and derivation of guideline recommendations (2). The current A.S.P.E.N. and SCCM guidelines included in this paper were derived from data obtained via literature searches by the authors through December 31, 2013. Although the committee was aware of landmark studies published after this date, these data were not included in this manuscript. The process by which the literature was evaluated necessitated a common end date for the search review. Adding a last-minute landmark trial would have introduced bias unless a formalized literature search was re-conducted for all sections of the manuscript. Target Patient Population for Guideline: The target of these guidelines is intended to be the adult (≥ 18 years) critically ill patient expected to require a length of stay (LOS) greater than 2 or 3 days in a medical ICU (MICU) or surgical ICU (SICU). The current guidelines were expanded to include a number of additional subsets of patients who met the above criteria, but were not included in the previous 2009 guidelines. Specific patient populations addressed by these expanded and updated guidelines include organ failure (pulmonary, renal, and liver), acute pancreatitis, surgical subsets (trauma, traumatic brain injury [TBI], open abdomen [OA], and burns), sepsis, postoperative major surgery, chronic critically ill, and critically ill obese. These guidelines are directed toward generalized patient populations but, like any other management strategy in the ICU, nutrition therapy should be tailored to the individual patient. Target Audience: The intended use of these guidelines is for all healthcare providers involved in nutrition therapy of the critically ill, primarily physicians, nurses, dietitians, and pharmacists. Methodology: The authors compiled clinical questions reflecting key management issues in nutrition therapy. A committee of multidisciplinary experts in clinical nutrition composed of physicians, nurses, pharmacists, and dietitians was jointly convened by the two societies.

/pdf/guidelines-for-the-provision-and-assessment-of-nutrition-1t9bnid4wv.pdf

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).

Hepatic steatosis as a potential risk factor for major hepatic resection.

Background

Long-term functional outcome after operative treatment of necrotizing pancreatitis (NP) has not been studied extensively.



Methods

Pancreatic function, performance status, recurrence of symptoms and other related problems were analysed in 44 consecutive patients successfully discharged from hospital after operative necrosectomy (1983–1995) and followed up completely for a mean of 5 years.



Results

Clinical pancreatic insufficiency developed in half the patients. Diabetes mellitus (11 patients), steatorrhoea (six) or both (five) were associated with a mean estimate of 52, 66 and 67 per cent parenchymal necrosis respectively. Normal pancreatic function was associated with 27 per cent parenchymal necrosis (P < 0·05). Diabetes worsened while steatorrhoea tended to improve over time. Abdominal pain and pancreatitis recurred in six and two patients respectively. Performance status worsened in four patients because of recurrent pancreatitis and severe steatorrhoea. Poor long-term performance was associated with a higher Acute Physiology And Chronic Health Evaluation II score on admission (mean 14 versus 9).



Conclusion

NP has prominent effects on long-term pancreatic exocrine and endocrine function in half the patients, but most preserve a good overall functional status. The development of pancreatic insufficiency varies with the extent of pancreatic parenchymal necrosis. © 1998 British Journal of Surgery Society Ltd

Long-term outcome of necrotizing pancreatitis treated by necrosectomy

Resection of hepatic metastases is the preferred treatment for selected patients after resection of primary colorectal carcinoma, but timing is controversial. This study was designed to compare outcomes of patients receiving concurrent resection of hepatic metastases and the primary colorectal tumor with those of patients receiving staged resection (within 6 months). We retrospectively analyzed medical records (1986–1999) of 96 consecutive patients with synchronously recognized primary carcinoma and hepatic metastases who underwent concurrent (64 patients) or staged (32 patients) colonic and hepatic resections performed at our institution. Concurrent and staged groups were similar in demographics, tumor grade, stage, preoperative comorbidity (cardiac and respiratory), characteristics of hepatic metastases, and single vs. multiple lesions. No significant differences were observed between groups (concurrent vs. staged) in type of colon resection (P = 0.45) or hepatic resection (P = 0.09), overall operative duration (mean, 430 vs. 427 minutes; P = 0.39), blood loss (mean, 890 vs. 889 ml; P = 0.87), volume of blood products transfused (mean, 326 vs. 185 ml; P = 0.08), perioperative morbidity (53 vs. 41 percent; P = 0.25), disease-free survival from date of hepatectomy (median, 13 vs. 13 months; P = 0.53), or overall survival from date of hepatectomy (median, 27 vs. 34 months; P = 0.52). There was no operative mortality. Overall duration of hospitalization was significantly shorter for concurrent than for staged resection (mean, 11 vs. 22 days; P ≤ 0.001). Concurrent colectomy and hepatectomy is safe and more efficient than staged resection and should be the procedure of choice for selected patients in medical centers with appropriate capacity and experience.

Concurrent vs. Staged Colectomy and Hepatectomy for Primary Colorectal Cancer With Synchronous Hepatic Metastases

methods From 1983 to 1995, 72 patients with necrotizing pancreatitis were treated with a general approach involving planned reoperative necrosectomies and interval abdominal wound closure using a zipper. results Hospital mortality was 25%. Multiple organ failure without sepsis caused early mortality in 3 of 4 patients and sepsis caused late mortality in 11 of the remaining 14. The mean number of reoperative necrosectomies/debridements was 2 (0 to 7). Fistulae developed in 25 patients (35%); 64% were treated conservatively. Recurrent intraabdominal abscesses developed in 9 patients (13%) but were drained percutaneously in 5. Hemorrhage required intervention in 13 patients (18%). Prognostic factors included APACHE-II score on admission P = 0.005), absence of postoperative hemorrhage ( P = 0.01), and peripancreatic tissue necrosis alone ( P conclusions The zipper approach effectively maximizes the necrosectomy and decreases the incidence of recurrent intraabdominal infection requiring reoperation. APACHE-II score ≥13, extensive parenchymal necrosis, and postoperative hemorrhage signify worse outcome.

Gregory G. Tsiotos

Papers

Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus

Hepatic steatosis as a potential risk factor for major hepatic resection.

Long-term outcome of necrotizing pancreatitis treated by necrosectomy

Concurrent vs. Staged Colectomy and Hepatectomy for Primary Colorectal Cancer With Synchronous Hepatic Metastases

Management of necrotizing pancreatitis by repeated operative necrosectomy using a zipper technique.