IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections (IWGDF/IDSA 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

Diagnosis of infection in the foot of patients with diabetes: A systematic review.

BACKGROUND: Securing an early accurate diagnosis of diabetic foot infections and assessment of their severity are of paramount importance since these infections can cause great morbidity and potential mortality and present formidable challenges in surgical and antimicrobial treatment. METHODS: In June 2022, we searched the literature using PubMed and EMBASE for published studies on the diagnosis of diabetic foot infection (DFI). On the basis of pre-determined criteria, we reviewed prospective controlled, as well as non-controlled, studies in English. We then developed evidence statements based on the included papers. RESULTS: We selected a total of 64 papers that met our inclusion criteria. The certainty of the majority of the evidence statements was low because of the weak methodology of nearly all of the studies. The available data suggest that diagnosing diabetic foot infections on the basis of clinical signs and symptoms and classified according to the International Working Group of the Diabetic Foot/Infectious Diseases Society of America scheme correlates with the patient's likelihood of the need for hospitalisation, lower extremity amputation, and risk of death. Elevated levels of selected serum inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein and procalcitonin are supportive, but not diagnostic, of soft tissue infection. Culturing tissue samples of soft tissues or bone, when care is taken to avoid contamination, provides more accurate microbiological information than culturing superficial (swab) samples. Although non-culture techniques, especially next-generation sequencing, are likely to identify more bacteria from tissue samples including bone than standard cultures, no studies have established a significant impact on the management of patients with DFIs. In patients with suspected diabetic foot osteomyelitis, the combination of a positive probe-to-bone test and elevated ESR supports this diagnosis. Plain X-ray remains the first-line imaging examination when there is suspicion of diabetic foot osteomyelitis (DFO), but advanced imaging methods including magnetic resonance imaging (MRI) and nuclear imaging when MRI is not feasible help in cases when either the diagnosis or the localisation of infection is uncertain. Intra-operative or non-per-wound percutaneous biopsy is the best method to accurately identify bone pathogens in case of a suspicion of a DFO. Bedside percutaneous biopsies are effective and safe and are an option to obtain bone culture data when conventional (i.e. surgical or radiological) procedures are not feasible. CONCLUSIONS: The results of this systematic review of the diagnosis of diabetic foot infections provide some guidance for clinicians, but there is still a need for more prospective controlled studies of high quality.

Interventions in the management of diabetes-related foot infections: A systematic review.

The optimal approaches to managing diabetic foot infections remain a challenge for clinicians. Despite an exponential rise in publications investigating different treatment strategies, the various agents studied generally produce comparable results, and high-quality data are scarce. In this systematic review, we searched the medical literature using the PubMed and Embase databases for published studies on the treatment of diabetic foot infections from 30 June 2018 to 30 June 2022. We combined this search with our previous literature search of a systematic review performed in 2020, in which the infection committee of the International Working Group on the Diabetic Foot searched the literature until June 2018. We defined the context of the literature by formulating clinical questions of interest, then developing structured clinical questions (Patients-Intervention-Control-Outcomes) to address these. We only included data from controlled studies of an intervention to prevent or cure a diabetic foot infection. Two independent reviewers selected articles for inclusion and then assessed their relevant outcomes and methodological quality. Our literature search identified a total of 5,418 articles, of which we selected 32 for full-text review. Overall, the newly available studies we identified since 2018 do not significantly modify the body of the 2020 statements for the interventions in the management of diabetes-related foot infections. The recent data confirm that outcomes in patients treated with the different antibiotic regimens for both skin and soft tissue infection and osteomyelitis of the diabetes-related foot are broadly equivalent across studies, with a few exceptions (tigecycline not non-inferior to ertapenem [±vancomycin]). The newly available data suggest that antibiotic therapy following surgical debridement for moderate or severe infections could be reduced to 10 days and to 3 weeks for osteomyelitis following surgical debridement of bone. Similar outcomes were reported in studies comparing primarily surgical and predominantly antibiotic treatment strategies in selected patients with diabetic foot osteomyelitis. There is insufficient high-quality evidence to assess the effect of various recent adjunctive therapies, such as cold plasma for infected foot ulcers and bioactive glass for osteomyelitis. Our updated systematic review confirms a trend to a better quality of the most recent trials and the need for further well-designed trials to produce higher quality evidence to underpin our recommendations.

IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections (IWGDF/IDSA 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

A Scoping Review of Foot Screening in Adults With Diabetes Mellitus Across Canada.

OBJECTIVES: Regular foot screening by a knowledgeable health-care provider is the cornerstone of ulcer and amputation prevention in people with diabetes. However, information on foot screening practices among Canadians with diabetes remains sparse. Therefore, we sought to synthesize available data on the frequency and approach to diabetic foot screening across Canada. METHODS: We conducted a scoping review by searching MEDLINE and Embase databases, alongside a grey literature search, for both English- and French-language reports. Data on patients' demographics, setting as well as the frequency of and approach to foot screening were abstracted. Title and abstract screening, full-text review and data abstraction were conducted in duplicate, with discrepancies resolved by a third reviewer. RESULTS: The search yielded 21 reports including information on diabetic foot screening practices in Canada. In a consolidated study sample of 13,388 Canadians with diabetes, 7,277 (53%) reported receiving a foot examination by a health-care provider at least once in the past year. The majority of reports did not provide information on the demographics of patients being screened or details on the approach to foot screening. No report mentioned the use of a triage algorithm applied to the results of foot screening. CONCLUSIONS: In this work, we identified the limited frequency and uncertain quality of diabetic foot screening across Canada. Further research should focus on better understanding disparities and barriers to regular diabetic foot screening.

Canadian Cardiovascular Society 2022 Guidelines for Peripheral Arterial Disease.

Patients with widespread atherosclerosis such as peripheral artery disease (PAD) have a high risk of cardiovascular and limb symptoms and complications, which affects their quality of life and longevity. Over the past 2 decades there have been substantial advances in diagnostics, pharmacotherapy, and interventions including endovascular and open surgical to aid in the management of PAD patients. To summarize the evidence regarding approaches to diagnosis, risk stratification, medical and intervention treatments for patients with PAD, guided by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework, evidence was synthesized, and assessed for quality, and recommendations provided-categorized as weak or strong for each prespecified research question. Fifty-six recommendations were made, with 27% (15/56) graded as strong recommendations with high-quality evidence, 14% (8/56) were designated as strong recommendations with moderate-quality evidence, and 20% (11/56) were strong recommendations with low quality of evidence. Conversely 39% (22/56) were classified as weak recommendations. For PAD patients, strong recommendations on the basis of high-quality evidence, include smoking cessation interventions, structured exercise programs for claudication, lipid-modifying therapy, antithrombotic therapy with a single antiplatelet agent or dual pathway inhibition with low-dose rivaroxaban and aspirin; treatment of hypertension with an angiotensin converting enzyme or angiotensin receptor blocker; and for those with diabetes, a sodium-glucose cotransporter 2 inhibitor should be considered. Furthermore, autogenous grafts are more effective than prosthetic grafts for surgical bypasses for claudication or chronic limb-threatening ischemia involving the popliteal or distal arteries. Other recommendations indicated that new endovascular techniques and hybrid procedures be considered in patients with favourable anatomy and patient factors, and finally, the evidence for perioperative risk stratification for PAD patients who undergo surgery remains weak.

A Population-Based Analysis of Diabetes-Related Care Measures, Foot Complications, and Amputation During the COVID-19 Pandemic in Ontario, Canada.

Importance: Deferred diabetic foot screening and delays in timely care of acute foot complications during the COVID-19 pandemic may have contributed to an increase in limb loss. Objective: To evaluate the association of the COVID-19 pandemic with diabetes-related care measures, foot complications, and amputation. Design, Setting, and Participants: This population-based cohort study included all adult residents of Ontario, Canada, with diabetes and compared the rates of selected outcomes from January 1, 2020, to February 23, 2021, vs January 1, 2019, to February 23, 2020. Main Outcomes and Measures: Comprehensive in-person diabetes care assessment, including foot examination; hemoglobin A1c (HbA1c) measurement; emergency department visit or hospitalization for diabetic foot ulceration, osteomyelitis, or gangrene; lower extremity open or endovascular revascularization; minor (toe or partial-foot) amputation; and major (above-ankle) leg amputation. Rates and rate ratios (RRs) comparing 2020-2021 vs 2019-2020 for each measure were calculated for 10-week periods, anchored relative to onset of the pandemic on March 11, 2020 (11th week of 2020). Results: On March 11, 2020, the study included 1 488 605 adults with diabetes (median [IQR] age, 65 [55-74] years; 776 665 [52.2%] men), and on March 11, 2019, the study included 1 441 029 adults with diabetes (median [IQR] age, 65 [55-74] years; 751 459 [52.1%] men). After the onset of the pandemic, rates of major amputation in 2020-2021 decreased compared with 2019-2020 levels. The RR for the prepandemic period from January 1 to March 10 was 1.05 (95% CI, 0.88-1.25), with RRs in the pandemic periods ranging from 0.86 (95% CI, 0.72-1.03) in May 20 to July 28 to 0.95 (95% CI, 0.80-1.13) in October 7 to December 15. There were no consistent differences in demographic characteristics or comorbidities of patients undergoing amputation in the 2020-2021 vs 2019-2020 periods. Rates of comprehensive in-person diabetes care assessment and HbA1c measurement declined sharply and remained below 2019-2020 levels (eg, in-person assessment, March 11 to May 19: RR, 0.28; 95% CI, 0.28-0.28). The rates of emergency department visits (eg, March 11 to May 19: RR, 0.67; 95% CI, 0.61-0.75), hospitalization (eg, March 11 to May 19: RR, 0.77; 95% CI, 0.68-0.87), open revascularization (eg, March 11 to May 19: RR, 0.66; 95% CI, 0.56-0.79), endovascular revascularization (March 11 to May 19: RR, 0.70; 95% CI, 0.61-0.81), and minor amputation (March 11 to May 19: RR, 0.70; 95% CI, 0.60-0.83) initially dropped but recovered to 2019-2020 levels over the study period. Conclusions and Relevance: In this population-based cohort study, disruptions in care related to the COVID-19 pandemic were not associated with excess leg amputations among people living with diabetes. As the pandemic ends, improved prevention and treatment of diabetic foot complications will be necessary to maintain these positive results.

The Impact of the Implementation of the Enhanced Recovery After Surgery (ERAS®) Program in an Entire Health System: A Natural Experiment in Alberta, Canada.

BACKGROUND: The Enhanced Recovery After Surgery (ERAS) program has been shown to reduce length of stay (LOS) in colorectal surgical patients in randomized trials. The impact outside of trial settings, or in subgroups of patients excluded from trials such as individuals with diabetes, is uncertain. We conducted this study to evaluate the impact of ERAS implementation in Alberta, Canada. METHODS: This is a retrospective cohort study and interrupted time series analysis using linked administrative data to examine LOS and postoperative outcomes in the 12 months pre- and post-implementation of ERAS in 2013 for all adults undergoing elective colorectal surgery. RESULTS: Of 2714 patients (mean age 60.4 years, 55% men) with similar demographics and comorbidity profiles in the pre/post-ERAS time periods, LOS was significantly shorter post-ERAS (8.5 vs. 9.5 days, p = 0.01; - 0.84 days [95% CI - 0.04 to - 1.64 days] after adjustment for age, sex, Charlson comorbidity score, procedure type, surgical approach, and hospital). However, interrupted time series demonstrated no significant level change (p = 0.30) or change in slope (p = 0.63) with ERAS implementation, consistent with continuation of an underlying secular trend of reductions in LOS over time. There were no significant differences (in multivariate analysis or ITS) in risk of 30-day death/readmission (14.3% post vs. 13.5% pre-ERAS, aOR 1.12, 95% CI 0.89-1.40), 30-day death/ED visit (27.2% post vs. 30.0% pre, aOR 0.93, 95% CI 0.78-1.10), or 30-day death/readmission/ED visit (27.8% post vs. 30.6% pre, aOR 0.93, 95% CI 0.78-1.10). The 428 patients with diabetes had longer LOS but exhibited no significant difference post- versus pre-ERAS (10.7 vs. 11.6 days, p = 0.53; p = 0.56 for level change and p = 0.66 for slope change on ITS). CONCLUSION: Although there was a secular trend toward decreasing LOS over time in Alberta, ERAS implementation was not associated with statistically significant changes in LOS or postoperative outcomes for all colorectal surgery patients or for those with diabetes. Our study highlights the importance of evaluating system changes (for both uptake and outcomes) rather than assuming trial benefits will translate directly into practice. Interventions to improve LOS and postoperative outcomes for patients with diabetes undergoing colorectal surgery are still needed even in the ERAS era.

Enhanced Recovery After Surgery (ERAS®) in Individuals with Diabetes: A Systematic Review.

BACKGROUND: Prevalence of diabetes in surgical patients is 10-40%. It is well recognized that they have higher rates of complications, and longer stays in hospital compared to patients without diabetes. Enhanced recovery after surgery (ERAS) is an evidence-based multimodal surgical care pathway that improves postoperative complications and length of stay in patients without diabetes. This review evaluates the evidence on whether individuals with diabetes would benefit from ERAS implementation. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE searched with no language restrictions applied. Conference proceedings and bibliographies were reviewed. Experts in the field were contacted, and www.clinicaltrials.gov searched for ongoing trials. SELECTION CRITERIA: Randomized controlled trials (RCT) looking at individuals with diabetes undergoing surgery randomized to ERAS® or conventional care. Non-randomized controlled trials, controlled before-after studies, interrupted time series, and cohort studies with concurrent controls were also considered. Two authors independently screened studies. RESULTS: The electronic search yielded 437 references. After removing duplicates, 376 were screened for eligibility. Conference proceedings and bibliographies identified additional references. Searching www.clinicaltrials.gov yielded 59 references. Contacting experts in the field identified no further studies. Fourteen full articles were assessed and subsequently excluded for the following reasons: used an intervention other than ERAS®, did not include patients with diabetes, or used an uncontrolled observational design. CONCLUSIONS: To date, the effects of ERAS® on patients with diabetes have not been rigorously evaluated. This review highlights the lack of evidence in this area and provides guidance on design for future studies.

Intranasal ipratropium bromide for the common cold.

BACKGROUND: The common cold is one of the most common illnesses in humans and constitutes an economic burden both in terms of productivity and expenditure for treatment. There is no proven cure for the common cold and symptomatic relief is the mainstay of treatment. The use of intranasal ipratropium bromide (IB) has been addressed in several studies and might prove an effective treatment for the common cold. OBJECTIVES: To determine the effect of IB versus placebo or no treatment on severity of rhinorrhoea and nasal congestion in children and adults with the common cold. Subjective overall improvement was another primary outcome and side effects (for example, dry mucous membranes, epistaxis and systemic anticholinergic effects) were reported as a secondary outcome. SEARCH METHODS: In this updated review we searched CENTRAL 2013, Issue 3, MEDLINE (1950 to March week 4, 2013), MEDLINE in-process and other non-indexed citations (8 April 2013), EMBASE (1974 to April 2013), AMED (1985 to April 2013), Biosis (1974 to February 2011) and LILACS (1985 to April 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing IB to placebo or no treatment in children and adults with the common cold. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We used a standardised form to extract relevant data and we contacted trial authors for additional information. MAIN RESULTS: Seven trials with a total of 2144 participants were included. Four studies (1959 participants) addressed subjective change in severity of rhinorrhoea. All studies were consistent in reporting statistically significant changes in favour of IB. Nasal congestion was reported in four studies and was found to have no significant change between the two groups. Two studies found a positive response in the IB group for the global assessment of overall improvement. Side effects were more frequent in the IB group, odds ratio (OR) 2.09 (95% confidence interval (CI) 1.40 to 3.11). Commonly encountered side effects included nasal dryness, blood tinged mucus and epistaxis. The overall risk of bias in the included studies was moderate. AUTHORS' CONCLUSIONS: For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well tolerated and self limiting. There is a need for larger, high-quality trials to determine the effectiveness of IB in relieving common cold symptoms.

Random error in cardiovascular meta-analyses: how common are false positive and false negative results?

BACKGROUND: Cochrane reviews are viewed as the gold standard in meta-analyses given their efforts to identify and limit systematic error which could cause spurious conclusions. The potential for random error to cause spurious conclusions in meta-analyses is less well appreciated. METHODS: We examined all reviews approved and published by the Cochrane Heart Group in the 2012 Cochrane Library that included at least one meta-analysis with 5 or more randomized trials. We used trial sequential analysis to classify statistically significant meta-analyses as true positives if their pooled sample size and/or their cumulative Z-curve crossed the O'Brien-Fleming monitoring boundaries for detecting a RRR of at least 25%. We classified meta-analyses that did not achieve statistical significance as true negatives if their pooled sample size was sufficient to reject a RRR of 25%. RESULTS: Twenty three (41%) of the 56 meta-analyses reported statistically significant results, and 19 (83%) were true positives. Of the 33 non-statistically significant meta-analyses, 12 (36%) were true negatives. Overall, 25 (45%) of the 56 published Cochrane reviews were too small to detect/rule out an effect size of at least 25% - 12 were acknowledged as such by their authors. Of the 22 meta-analyses which were reported to be conclusive by their authors, 12 (55%) contained insufficient data to detect/rule out a 25% relative treatment effect. CONCLUSION: False positive and false negative meta-analyses are common but infrequently recognized, even among methodologically robust reviews published by the Cochrane Heart Group. Meta-analysts and readers should incorporate trial sequential analysis when interpreting results.

Intranasal ipratropium bromide for the common cold.

BACKGROUND: The common cold is one of the most common illnesses in humans and constitutes an economic burden both in terms of productivity and expenditure for treatment. There is no proven cure for the common cold and symptomatic relief is the mainstay of treatment. The use of intranasal ipratropium bromide (IB) has been addressed in several studies and might prove an effective treatment for the common cold. OBJECTIVES: To determine the effect of IB versus placebo or no treatment on severity of rhinorrhoea and nasal congestion in children and adults with the common cold. Subjective overall improvement was another primary outcome and side effects were reported as a secondary outcome. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 1) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to January week 4, 2011), MEDLINE in-process and other non-indexed citations (February 2011), EMBASE (1974 to February 2011), AMED (1985 to February 2011), Biosis (1974 to February 2011) and LILACS (1985 to February 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing IB to placebo or no treatment in children and adults with the common cold. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We used a standardised form to extract relevant data and we contacted trial authors for additional information. MAIN RESULTS: Seven trials with a total of 2144 participants were included. Four studies (1959 participants) addressed subjective change in severity of rhinorrhoea. All studies were consistent in reporting statistically significant changes in favour of IB. Nasal congestion was reported in four studies and was found to have no significant change between the two groups. Two studies found a positive response in the IB group for the global assessment of overall improvement. Side effects were more frequent in the IB group, odds ratio (OR) 2.09 (95% confidence interval (CI) 1.40 to 3.11). Commonly encountered side effects included nasal dryness, blood tinged mucus and epistaxis. AUTHORS' CONCLUSIONS: For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well-tolerated and self-limiting. There is a need for larger, high-quality trials to determine the effectiveness of IB in relieving common cold symptoms.

Enteral versus parenteral nutrition for acute pancreatitis.

BACKGROUND: Acute pancreatitis creates a catabolic stress state promoting a systemic inflammatory response and nutritional deterioration. Adequate supply of nutrients plays an important role in recovery. Total parenteral nutrition (TPN) has been standard practice for providing exogenous nutrients to patients with severe acute pancreatitis. However, recent data suggest that enteral nutrition (EN) is not only feasible, but safer and more effective.Therefore, we sought to update our systematic review to re-evaluate the level of evidence. OBJECTIVES: To compare the effect of TPN versus EN on mortality, morbidity and length of hospital stay in patients with acute pancreatitis. SEARCH STRATEGY: Trials were identified by computerized searches of The Cochrane Controlled Trials Register, MEDLINE, and EMBASE. Additional studies were identified by searching Scisearch, bibliographies of review articles and identified trials. The search was undertaken in August 2000 and updated in September 2002, October 2003, November 2004 and November 2008. No language restrictions were applied. SELECTION CRITERIA: Randomized clinical trials comparing TPN to EN in patients with acute pancreatitis. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed trial quality. A standardized form was used to extract relevant data. MAIN RESULTS: Eight trials with a total of 348 participants were included. Comparing EN to TPN for acute pancreatitis, the relative risk (RR) for death was 0.50 (95% CI 0.28 to 0.91), for multiple organ failure (MOF) was 0.55 (95% CI 0.37 to 0.81), for systemic infection was 0.39 (95% CI 0.23 to 0.65), for operative interventions was 0.44 (95% CI 0.29 to 0.67), for local septic complications was 0.74 (95% CI 0.40 to 1.35), and for other local complications was 0.70 (95% CI 0.43 to 1.13). Mean length of hospital stay was reduced by 2.37 days in EN vs TPN groups (95% CI -7.18 to 2.44). Furthermore, a subgroup analysis for EN vs TPN in patients with severe acute pancreatitis showed a RR for death of 0.18 (95% CI 0.06 to 0.58) and a RR for MOF of 0.46 (95% CI 0.16 to 1.29). AUTHORS' CONCLUSIONS: In patients with acute pancreatitis, enteral nutrition significantly reduced mortality, multiple organ failure, systemic infections, and the need for operative interventions compared to those who received TPN. In addition, there was a trend towards a reduction in length of hospital stay. These data suggest that EN should be considered the standard of care for patients with acute pancreatitis requiring nutritional support.