Increased risk of adverse events in patients with low-on clopidogrel platelet reactivity after percutaneous coronary intervention: A systematic review and meta-analysis.

BACKGROUND: Clinical evidence has been controversial regarding the influence of low platelet reactivity (LPR), ischemic and bleeding outcomes among patients receiving coronary stent implantation. Hence, the present study performed a meta-analysis to systematically evaluate the significance of LPR on adverse cardiovascular events. METHODS: MEDLINE, EMBASE and CENTRAL databases were searched up to November 2020 for relevant studies including patients with acute coronary syndrome undergoing percutaneous coronary intervention. LPR was the exposed arm while the non-LPR group represented the control. The primary outcome of interest was bleeding risk including major and minor bleeding events. Secondary outcomes included all-cause mortality, repeated revascularization, nonfatal myocardial infarction, and stent thrombosis. Study-level outcomes were evaluated in random-effect models. RESULTS: A total of 20 studies with 19,064 patients were included. Pooled analysis showed that LPR was associated with an increased bleeding risk (relative risk [RR] 2.80, 95% confidence interval [CI] 1.95-4.02, p < 0.01). Patients with LPR had a lower risk of non-fatal myocardial infarction (RR 0.59, 95% CI 0.38-0.91, p < 0.05) and of serious vascular events (RR 0.50, 95% CI 0.30-0.84, p < 0.01). CONCLUSIONS: Low platelet reactivity is associated with an increased bleeding risk of patients who underwent coronary stent implantation. The results suggest possible benefits of this marker in risk stratification, with potential improvement in risk prediction. There are potential advantages using combinations with other factors in prediction models, however, they require further study. PROSPERO registration number: CRD42019136393).

Geno- and phenotypic characteristics and clinical outcomes of CACNA1C gene mutation associated Timothy syndrome, "cardiac only" Timothy syndrome and isolated long QT syndrome 8: A systematic review.

Background: Mutations in the CACNA1C gene-encoding for the major Ca2+ channel of the heart-may exhibit a variety of clinical manifestations. These include typical or atypical Timothy syndromes (TS) which are associated with multiple organ manifestations, and cardiac involvement in form of malignant arrhythmias, QTc prolongation, or AV block. "Cardiac only" Timothy syndrome (COTS) shows no extracardiac manifestation, whereas some CACNA1C gene mutations are associated with QTc prolongation alone (isolated long QT syndrome 8, LQT8). Methods: A systematic search of the literature reporting cases of CACNA1C gene mutation associated syndromes, including TS, COTS and isolated LQT8 via major databases published from 2004 through 2019 was performed. Detailed patient-level phenotypic and genotypic characteristics, as well as long-term outcome measures were collected and compared between pre-specified patient groups, defined both on phenotype and genotype. Results: A total of 59 TS, 6 COTS, and 20 isolated LQT8 index cases were identified. Apart of syndactyly or baldness, there were no major differences regarding clinical manifestations or outcome measures between TS subtypes, either defining TS subtypes on the genotype or based on the phenotype. Both subtypes were characterized by an extreme degree of QTc prolongation (median ≥600 ms) which were reflected in high major adverse cardiac event rate. On the other hand, there were marked differences between TS, COTS, and isolated LQT8. Timothy syndrome was characterized by a much earlier disease onset, much more pronounced QTc prolongation and much higher mortality rate than COTS or isolated LQT8. Similar differences were observed comparing CACNA1C exon 8/8A vs. non-exon 8/8A mutation carriers. TS showed a high degree of genetic homogeneity, as the p.Gly406Arg mutation either in exon 8 or exon 8A alone was responsible for 70% of the cases. Conclusions: Clinical phenotypes associated with mutations in the CACNA1C gene show important clinical differences. Timothy syndrome is associated with the most severe clinical phenotype and with the highest risk of morbidity and mortality. However, distinguishing TS subtypes, in any form, are not supported by our data. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020184737].

Predictive value of tachycardia for mortality in trauma-related haemorrhagic shock: a systematic review and meta-regression.

OBJECTIVES: Heart rate (HR) is one of the physiological variables in the early assessment of trauma-related haemorrhagic shock, according to Advanced Trauma Life Support (ATLS). However, its efficiency as predictor of mortality is contradicted by several studies. Furthermore, the linear association between HR and the severity of shock and blood loss presented by ATLS is doubtful. This systematic review aims to update current knowledge on the role of HR in the initial haemodynamic assessment of patients who had a trauma. DESIGN: This study is a systematic review and meta-regression that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. DATA SOURCES: EMBASE, MEDLINE, CENTRAL and Web of Science databases were systematically searched through on 1 September 2020. ELIGIBILITY CRITERIA: Papers providing early HR and mortality data on bleeding patients who had a trauma were included. Patient cohorts were considered haemorrhagic if the inclusion criteria of the studies contained transfusion and/or positive focused assessment with sonography for trauma and/or postinjury haemodynamical instability and/or abdominal gunshot injury. Studies on burns, traumatic spinal or brain injuries were excluded. Papers published before January 2010 were not considered. DATA EXTRACTION AND SYNTHESIS: Data extraction and risk of bias were assessed by two independent investigators. The association between HR and mortality of patients who had a trauma was assessed using meta-regression analysis. As subgroup analysis, meta-regression was performed on patients who received blood products. RESULTS: From a total of 2017 papers, 19 studies met our eligibility criteria. Our primary meta-regression did not find a significant relation (p=0.847) between HR and mortality in patients who had a trauma with haemorrhage. Our subgroup analysis included 10 studies, and it could not reveal a linear association between HR and mortality rate. CONCLUSIONS: In accordance with the literature demonstrating the multiphasic response of HR to bleeding, our study presents the lack of linear association between postinjury HR and mortality. Modifying the pattern of HR derangements in the ATLS shock classification may result in a more precise teaching tool for young clinicians.

Weight reduction added to CPAP decreases blood pressure and triglyceride level in OSA: Systematic review and meta-analysis.

Obstructive sleep apnea (OSA) is associated with treatment-resistant hypertension and high cardiovascular risk. Continuous positive airway pressure (CPAP) fails to reduce cardiovascular risks consistently. Obesity and OSA show reciprocal association and they synergistically increase hypertension via different pathways. Our meta-analysis aimed to assess the cardiovascular benefits of combining weight loss (WL) with CPAP (vs. WL or CPAP alone) in OSA. Outcomes included systolic and diastolic blood pressure (BP) and blood lipid parameters. We explored Medline, Embase, Cochrane, and Scopus. Eight randomized controlled studies (2627 patients) were included. The combined therapy decreased systolic BP more than CPAP alone. Weighted mean difference (WMD) for CPAP + WL versus CPAP was -8.89 mmHg, 95% confidence interval (95% CI; -13.67 to -4.10, p < 0.001) for systolic BP. For diastolic BP, this decrease was not significant. In case of blood lipids, the combined treatment decreased triglyceride levels more than CPAP alone (WMD = -0.31, 95% CI -0.58 to -0.04, p = 0.027). On the other hand, addition of CPAP to WL failed to suppress BP further. The certainty of evidence according to GRADE was very low to moderate. In conclusion, our results showed that the addition of WL to CPAP significantly improved BP and blood lipid values in OSA. On the other hand, the addition of CPAP to WL could not significantly improve BP or blood lipid values. Review protocol: PROSPERO CRD42019138998.

Efficacy of first-line treatment options in transplant-ineligible multiple myeloma: A network meta-analysis.

BACKGROUND: Despite major therapeutic advances, the rational choice of the most appropriate first-line regimen in newly diagnosed transplant-ineligible multiple myeloma (TIE-MM) is currently undefined. AIM: We aimed to identify the most effective first-line treatment for TIE-MM patients. METHODS: A total of 37 articles, including 34 treatments and 16,681 patients, were included in this Bayesian network meta-analysis. The outcomes of interest were risk ratios (RR) for progression-free survival (PFS) and overall survival (OS). RESULTS: Based on surface under cumulative ranking curve values, daratumumab-bortezomib-melphalan-prednisone (Dara-VMP) and daratumumab-lenalidomide-dexamethasone (Dara-Rd28) showed superiority compared to other combinations regarding 12-, 24-, 36-, and 48-month PFS. Dara-VMP also ranked first for 12-, 24-, 36-, and 48-month OS. CONCLUSION: Our finding supports the incorporation of daratumumab into first-line regimens. Additionally, these results highlight the relative benefit of incorporating novel agents like monoclonal antibodies, immunomodulatory derivatives, and proteasome inhibitors in combination with the currently existing treatment options.

Oral Proton Pump Inhibitors May Be as Effective as Intravenous in Peptic Ulcer Bleeding: A Systematic Review and Meta-analysis.

INTRODUCTION: Current guidelines recommend intravenous (IV) proton pump inhibitor (PPI) therapy in peptic ulcer bleeding (PUB). We aimed to compare the efficacy of oral and IV administration of PPIs in PUB. METHODS: We performed a systematic search in 4 databases for randomized controlled trials, which compared the outcomes of oral PPI therapy with IV PPI therapy for PUB. The primary outcomes were 30-day recurrent bleeding and 30-day mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes, while weighted mean differences (WMDs) with CI were calculated for continuous outcomes in meta-analysis. The protocol was registered a priori onto PROSPERO (CRD42020155852). RESULTS: A total of 14 randomized controlled trials reported 1,951 peptic ulcer patients, 977 and 974 of which were in the control and intervention groups, respectively. There were no statistically significant differences between oral and IV administration regarding 30-day rebleeding rate (OR = 0.96, CI: 0.65-1.44); 30-day mortality (OR = 0.70, CI: 0.35-1.40); length of hospital stay (WMD = -0.25, CI: -0.93 to -0.42); transfusion requirements (WMD = -0.09, CI: -0.07 to 0.24); need for surgery (OR = 0.91, CI: 0.40-2.07); further endoscopic therapy (OR = 1.04, CI: 0.56-1.93); and need for re-endoscopy (OR = 0.81, CI: 0.52-1.28). Heterogeneity was negligible in all analysis, except for the analysis on the length of hospitalization (I2 = 82.3%, P = 0.001). DISCUSSION: Recent evidence suggests that the oral administration of PPI is not inferior to the IV PPI treatment in PUB after endoscopic management, but further studies are warranted.

Systematic review with meta-analysis: the effects of immunomodulator or biological withdrawal from mono- or combination therapy in inflammatory bowel disease.

BACKGROUND: Withdrawal of treatment is a common therapeutic problem in patients with long-standing remission of inflammatory bowel disease. AIMS: To evaluate the relapse rate in patients with quiescent inflammatory bowel disease after cessation of biologic or immunomodulator therapy. METHODS: We searched five databases for studies evaluating disease relapse after withdrawal of monotherapy or a drug from combination therapy in Crohn's disease or ulcerative colitis. In meta-analysis, risk ratios (RR) were calculated with 95% confidence intervals (CI). RESULTS: Ten randomised controlled trials (587 patients) were included in the meta-analysis, and another nine studies in systematic review. Withdrawal of immunomodulator monotherapy resulted in a significantly higher risk of relapse within 24 months of follow-up compared to ongoing therapy in Crohn's disease, but not in ulcerative colitis (RR = 2.06, CI: 1.53-2.77 and RR = 1.39, CI: 0.85-2.26, respectively). Trial sequential analysis indicated that further studies with similar design are unlikely to change the significant association on relapse rates after withdrawing immunomodulator monotherapy in patients with Crohn's disease. Discontinuation of an immunomodulator from combination with biologics did not show a higher risk of relapse than continuation of both drugs (RR = 1.30, CI: 0.81-2.08). The relapse rate increased after withdrawal of biologic monotherapy, whereas contradictory results were observed after biologic withdrawal from combination regimens. CONCLUSION: Continuing immunomodulator monotherapy should remain the preferred approach among patients with Crohn's disease, although long-term toxicity is a concern. Further randomised controlled trials are warranted in ulcerative colitis and on combination regimens including biologics.

ERCP is more challenging in cases of acute biliary pancreatitis than in acute cholangitis - Analysis of the Hungarian ERCP registry data.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an important therapeutic modality in acute biliary pancreatitis (ABP) cases with cholangitis or ongoing common bile duct obstruction. Theoretically, inflammation of the surrounding tissues would result in a more difficult procedure. No previous studies examined this hypothesis. OBJECTIVES: ABP and acute cholangitis (AC) without ABP cases were compared to assess difficulty of ERCP. METHODS: The rate of successful biliary access, advanced cannulation method, adverse events, cannulation and fluoroscopy time were compared in 240 ABP cases and 250 AC cases without ABP. Previous papillotomy, altered gastroduodenal anatomy, and cases with biliary stricture were excluded. RESULTS: Significantly more pancreatic guidewire manipulation (adjusted odds ratio (aOR) 1.921 [1.241-2.974]) and prophylactic pancreatic stent use (aOR 4.687 [2.415-9.098]) were seen in the ABP than in AC group. Average cannulation time in the ABP patients (248 vs. 185 s; p = 0.043) were longer than in AC cases. No difference was found between biliary cannulation and adverse events rates. CONCLUSION: ERCP in ABP cases seem to be more challenging than in AC. Difficult biliary access is more frequent in the ABP cases which warrants the involvement of an experienced endoscopist.

Relative performance of various biomaterials used for maxillary sinus augmentation: A Bayesian network meta-analysis.

OBJECTIVES: To assess the histomorphometric outcomes obtained in randomized clinical trials (RCTs) with different biomaterials used for maxillary sinus augmentation (MSA). MATERIALS AND METHODS: A search of the existing medical literature until October 1, 2019, was performed. Inclusion criteria were (a) RCTs assessing a two-stage MSA from the lateral approach using autologous bone or biomaterials for grafting and (b) reported histomorphometric outcomes based on crestal bone core biopsy samples. The Bayesian method was used to perform pairwise meta-analyses and network meta-analysis (NMA). The primary outcome, the new bone percentage (NB %), was calculated as mean differences with 95% credible intervals. The interventions were ranked by their posterior probability by calculating the surface under the cumulative ranking curve values. RESULTS: Thirty-four RCTs (842 MSAs) were included in the analysis with a normal healing period (5-8 months). All comparisons were presented in a league table. On the basis of the ranking probability, the most effective bone grafting material for NB% was bovine xenograft + bone marrow concentrate (BMC) (81%), followed by bovine xenograft + platelet-rich plasma (PRP) (77%), bioactive glass ceramic + autologous bone 1:1 (70%), nanocrystalline hydroxyapatite in silica gel (70%), and bioactive glass ceramic (70%). Autologous bone graft alone took the twelfth position with 57%. CONCLUSION: Within the limitations of the present NMA, the analysis did not confirm autologous bone alone as the gold standard for MSA and showed superiority of composite grafts such as bovine xenograft + BMC after 5-8 months of healing.

Oral Treatment With Bisphosphonates of Osteoporosis Does Not Increase the Risk of Severe Gastrointestinal Side Effects: A Meta-Analysis of Randomized Controlled Trials.

Introduction: Bisphosphonates (BPs) are first-line therapy for osteoporosis. Adherence is usually low in chronic, asymptomatic diseases, but gastrointestinal (GI) side-effects can also contribute to low adherence in BP therapy and may necessitate a review by a gastroenterologist with or without gastroscopy. Aims: Our meta-analysis aims to determine the risk of severe GI adverse events due to oral BP therapy in osteoporotic patients. Methods: A systematic search was conducted in three databases up to September 2020 for randomized controlled trials (RCTs) detailing GI adverse events in adults with osteoporosis on BP compared to placebo. Risk ratios (RRs) with 95% confidence intervals (CI) were calculated for non-severe and severe adverse events indicating endoscopic procedure with the random-effects model. Statistical heterogeneity was assessed using chi2 and I2 statistics. Results: Forty-two RCTs with 39,047 patients with 9,999 non-severe and 1,503 severe GI adverse events were included. The incidence of non-severe and severe adverse events ranged between 0.3-54.9 and 0-10.3%, respectively. There was no difference between BP and control groups in terms of the risk of non-severe or severe side effects: RR=1.05 (CI: 0.98-1.12), I2 = 48.1%, and RR=1.01 (CI: 0.92-1.12), I2 = 0.0%, respectively. Subgroup analysis of the most commonly used BP, once-weekly alendronate 70 mg, revealed an association between bisphosphonates and the risk of non-severe GI adverse events, RR=1.16 (CI: 1.00-1.36), I2 = 40.7%, while the risk of severe GI side effects was not increased in this subgroup, RR=1.20 (CI: 0.83-1.74), I2 = 0.0%. Conclusion: Our results show that bisphosphonates do not increase the risk of severe GI adverse events. However, the marked variability of the screening for side effects in the included studies, and the fact that in most of the studies GI diseases were exclusion criteria limits the strenght of evidence of our results. The conclusions drawn from the meta-analysis are therefore restricted to selected populations, and the results must be interpreted with caution.

Hypertriglyceridemia-induced acute pancreatitis: A prospective, multicenter, international cohort analysis of 716 acute pancreatitis cases.

BACKGROUND: Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. METHODS: AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (<1.7 mmol/l, 1.7-2.19 mmol/l, 2.2-5.59 mmol/l, 5.6-11.29 mmol/l, 11.3-22.59 mmol/l, ≥22.6 mmol/l). RESULTS: Hypertriglyceridemia (≥1.7 mmol/l) presented in 30.6% of the patients and was significantly and dose-dependently associated with younger age and male gender. In 7.7% of AP cases, hypertriglyceridemia was considered as a causative etiological factor (≥11.3 mmol/l); however, 43.6% of these cases were associated with other etiologies (alcohol and biliary). Hypertriglyceridemia was significantly and dose-dependently related to obesity and diabetes. The rates of local complications and organ failure and maximum CRP level were significantly and dose-dependently raised by hypertriglyceridemia. Triglyceride above 11.3 mmol/l was linked to a significantly higher incidence of moderately severe AP and longer hospital stay, whereas triglyceride over 22.6 mmol/l was significantly associated with severe AP as well. CONCLUSION: Hypertriglyceridemia dose-dependently aggravates the severity and related complications of AP. Diagnostic workup for hypertriglyceridemia requires better awareness regardless of the etiology of AP.

Antimicrobial Efficacy of Chlorhexidine and Sodium Hypochlorite in Root Canal Disinfection: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: We aimed to compare the antimicrobial efficacy of chlorhexidine (CHX) and sodium hypochlorite (NaOCl), 2 irrigants routinely used in root canal therapy of permanent teeth. METHODS: Electronic databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, were searched for randomized controlled trials published until March 2020. The meta-analysis of relative risk (RR) and standardized mean difference (SMD) was performed using a random effects model with a 95% confidence interval (CI). Subgroup analysis was performed for culture and molecular methods of bacterial detection. RESULTS: The literature search yielded 2110 records without duplicates. Eight studies were eligible for a systematic review. No significant differences in the incidence of samples with positive bacterial growth after irrigation (RR = 1.003; 95% CI, 0.729-1.380; P = .987) and mean bacterial number changes (SMD = 0.311; 95% CI, -0.368 to 0.991; P = .369) were observed between CHX and NaOCl in the culture and molecular subgroups. Heterogeneity in RR (I2 = 0%, P = .673) was low among studies, whereas considerable heterogeneity was observed in the analysis of SMD (I2 = 76.336%, P = .005). CONCLUSIONS: Our findings suggest that both CHX and NaOCl can reduce bacterial infections after irrigation without any significant difference in antimicrobial efficacy between them. Although CHX and NaOCl showed similar efficacy, their molecular mechanisms were different. Therefore, they can be used as the main antibacterial root canal irrigants. However, our results were limited by inconsistencies among retrieved articles and a lack of clinically relevant outcomes. Further well-designed clinical studies are warranted to supplement our results.

Hydroxyapatite-coated implants provide better fixation in total knee arthroplasty. A meta-analysis of randomized controlled trials.

BACKGROUND: The potential advantages of hydroxyapatite (HA)-coated cementless total knee arthroplasty (TKA) implants are bone stock preservation and biological fixation. Studies comparing the outcomes of HA-coated cementless, non HA-coated cementless (uncemented) and cemented TKA implants reported contradictory data. Our aim was to provide a comparison of the effects of HA coating of tibial stem on the stability and functionality of TKA implants. METHODS: A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the CENTRAL databases up to May 31st, 2019. The primary outcome was Maximum Total Point Motion (MTPM) of the tibial stem. This parameter is determined by radiosterometric analysis and refers to the migration pattern of the prosthesis stems. The clinical outcomes of the implanted joints were evaluated by the Knee Society Knee Score (KSS) and the Knee Society Function Score (KFS). Weighted mean difference (WMD) with 95% confidence interval (CI) were calculated with the random-effects model. RESULTS: Altogether, 11 randomized controlled trials (RCTs) with 902 patients for primary TKA implants were included. There was a statistically significant difference in the MTPM values with the use of HA-coated and uncoated uncemented implants (WMD = +0.28, CI: +0.01 to +0.56, P<0.001). However, HA-coated stems showed significantly higher migration when compared with the cemented prostheses (WMD = -0.29, CI: -0.41 to -0.16, P<0.001). The KSS values of HA-coated implants were significantly higher than those for the uncemented implants; moreover, KSS and KFS outcome scores were statistically not different between the HA-coated and cemented prosthesis cases. CONCLUSION: HA-coating yields better stability than other, uncemented prostheses. More importantly, the HA-coating is not outperformed by cemented prosthesis in providing good functional outcome.

Pre-transplant Sarcopenic Obesity Worsens the Survival After Liver Transplantation: A Meta-Analysis and a Systematic Review.

Background: The rising prevalence of cirrhotic cases related to non-alcoholic steatohepatitis has led to an increased number of cirrhotic patients with coexistence of obesity and muscle mass loss, known as sarcopenic obesity (SO). In patients undergoing liver transplantation (LT), the presence of SO may worsen prognosis, and increase morbidity and mortality. Objective: We aimed to evaluate the effect of the presence of pre-transplant SO on the outcomes of LT. Methods: A comprehensive search was performed in seven medical databases for studies comparing morbidity and mortality of patients with and without SO after LT. The primary outcome was overall mortality in the short- (1 year), intermediate- (3 years), and long- (5 years) term. We calculated pooled relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was quantified with I2-statistics. Results: Based on the analysis of 1,515 patients from three articles, SO increased overall mortality compared to non-SO at short-, intermediate-, and long-term follow-up (RR = 2.06, 95% CI: 1.28-3.33; RR = 1.67, 95% CI: 1.10-2.51; and RR = 2.08, 95% CI: 1.10-3.93, respectively) without significant between-study heterogeneity for the short- and intermediate- term (I2 = 0.0% for both) and considerable heterogeneity for long-term follow-up (I2 = 81.1%). Conclusion: Pre-transplant SO proved to be a risk factor after LT and was associated with two times higher mortality at short- and long- term follow-up. Since SO worsens the prognosis of patients after LT, the inclusion of body composition assessment before LT may help to plan a more individualized nutritional treatment, physiotherapy, and postoperative care and may improve morbidity and mortality.

A Multicenter, International Cohort Analysis of 1435 Cases to Support Clinical Trial Design in Acute Pancreatitis.

BACKGROUND: C-reactive protein level (CRP) and white blood cell count (WBC) have been variably used in clinical trials on acute pancreatitis (AP). We assessed their potential role. METHODS: First, we investigated studies which have used CRP or WBC, to describe their current role in trials on AP. Second, we extracted the data of 1435 episodes of AP from our registry. CRP and WBC on admission, within 24 h from the onset of pain and their highest values were analyzed. Descriptive statistical tools as Kruskal-Wallis, Mann-Whitney U, Levene's F tests, Receiver Operating Characteristic (ROC) curve analysis and AUC (Area Under the Curve) with 95% confidence interval (CI) were performed. RESULTS: Our literature review showed extreme variability of CRP used as an inclusion criterion or as a primary outcome or both in past and current trials on AP. In our cohort, CRP levels on admission poorly predicted mortality and severe cases of AP; AUC: 0.669 (CI:0.569-0.770); AUC:0.681 (CI: 0.601-0.761), respectively. CRP levels measured within 24 h from the onset of pain failed to predict mortality or severity; AUC: 0.741 (CI:0.627-0.854); AUC:0.690 (CI:0.586-0.793), respectively. The highest CRP during hospitalization had equally poor predictive accuracy for mortality and severity AUC:0.656 (CI:0.544-0.768); AUC:0.705 (CI:0.640-0.769) respectively. CRP within 24 h from the onset of pain used as an inclusion criterion markedly increased the combined event rate of mortality and severe AP (13% for CRP > 25 mg/l and 28% for CRP > 200 mg/l). CONCLUSION: CRP within 24 h from the onset of pain as an inclusion criterion elevates event rates and reduces the number of patients required in trials on AP.