World J Surg https://doi.org/10.1007/s00268-022-06533-w ORIGINAL SCIENTIFIC REPORT Elevated Serum Triglyceride Levels in Acute Pancreatitis: A Parameter to be Measured and Considered Early Nils Jimmy Hidalgo1 • Elizabeth Pando1 • Piero Alberti1 • Laura Vidal1 • Rodrigo Mata1 • Nair Fernandez1 • Maria Jose Gomez-Jurado1 • Cristina Dopazo1 • Laia Blanco1 • Stephanie Tasayco2 • Xavier Molero2 • Joaquim Balsells1 • Ramon Charco1 Accepted: 24 February 2022 Ó The Author(s) 2022 Abstract Background The value of serum triglycerides (TGs) related to complications and the severity of acute pancreatitis (AP) has not been clearly defined. Our study aimed to analyze the association of elevated levels of TG with complications and the severity of AP. Methods The demographic and clinical data of patients with AP were prospectively analyzed. TG levels were measured in the first 24 h of admission. Patients were divided into two groups: one with TG values of\200 mg/dL and another with TGC200 mg/dL. Data on the outcomes of AP were collected. Results From January 2016 to December 2019, 247 cases were included: 200 with TG\200 mg/dL and 47 with TGC200 mg/dL. Triglyceride levelsC200 mg/dL were associated with respiratory failure (21.3 vs. 10%, p=0.033), renal failure (23.4 vs. 12%, p=0.044), cardiovascular failure (19.1 vs. 7.5%, p=0.025), organ failure (34 vs. 18.5%, p=0.02), persistent organ failure (27.7 vs. 9.5%, p=0.001), multiple organ failure (19.1 vs. 8%, p=0.031), moderately severe and severe AP (68.1 vs. 40.5%, p=0.001), pancreatic necrosis (63.8 vs. 34%, p\0.001), and admission to the intensive care unit (27.7 vs. 9.5%, p=0.003). In the multivariable analysis, a TG level ofC200 mg/dL was inde- pendently associated with respiratory, renal, and cardiovascular failure, organ failure, persistent organ failure, multiple organ failure, pancreatic necrosis, severe pancreatitis, and admission to the intensive care unit (p\0.05). Conclusions In our cohort, TGC200 mg/dL was related to local and systemic complications. Early determinations of TG levels in AP could help identify patients at risk of complications. & Elizabeth Pando Cristina Dopazo epando@vhebron.net cdopazo@vhebron.net Nils Jimmy Hidalgo Laia Blanco nhidalgo@vhebron.net lblanco@vhebron.net Piero Alberti Stephanie Tasayco palberti@vhebron.net stasayco@vhebron.net Laura Vidal Xavier Molero l.vidal@vhebron.net xmolero@vhebron.net Rodrigo Mata Joaquim Balsells rjmatmat@vhebron.net joabalse@vhebron.net Nair Fernandez Ramon Charco nfernandes@vhebron.net rcharco@vhebron.net Maria Jose Gomez-Jurado m.gomez.4@vhebron.net 123 World J Surg Introduction abdominal pain, (2) Serum amylase or lipase more than 3 times the normal values, and (3) Contrast computed Acute pancreatitis (AP) is a complex inflammatory disease tomography (CT) with radiological findings suggestive of that affects the pancreas, peripancreatic tissue, and distant pancreatitis. When CT was not performed, pancreatic organs [1]. The worldwide incidence is approximately 70 magnetic resonance imaging (MRI) and abdominal ultra- cases per 100,000 individuals [2], with a growing number sound (US) with signs of pancreatitis were admitted. of hospitalizations every year in the world [3, 4]. Patients underwent the measurement of TG levels in the The clinical course of AP can range from relatively mild first 24 h of admission. and self-limited disease with uneventful and brief hospi- talization [5] to severe disease (15–20%), complicated by Exclusion criteria persistent or multisystem organ failure [6–8]. According to the revised Atlanta classification, severity is determined by Patients with AP whose etiology was hypertriglyceridemia local or systemic complications and can be classified into (HTG) syndrome, patients with another major disease three groups: mild, moderately severe, and severe [8]. coexisting with AP (upper gastrointestinal bleeding that Mortality continues to be high, with values between 10 and required an invasive endoscopic, radiological, or surgical 39%, in severe forms of the disease [9–11]. procedure or that involved duodenal perforation or perfo- The main causes of AP are gallstone disease (40–60%) ration of the bile duct), patients with another pathology not [12] and alcohol abuse, among other factors [13]. It has related to AP (periampullary neoplasia or neoplasia of the also been observed that elevated levels of serum triglyc- proximal or middle third of the biliary tract, or serious eride (TG) are commonly present in the early stage of acute infectious pathology), transferred patients, and patients biliary or alcoholic pancreatitis, but its clinical significance who arrived to the emergency department more than 72 h is still unknown. Only a few studies have observed the after the onset of symptoms. relationship between elevated levels of TG and complica- These inclusion and exclusion criteria reduce the bias of tions in AP, with contradictory results [14–17]. including patients with prolonged disease, avoid alterations Research on new risk factors for complications and in TG values that can occur after 48 h due to other factors mortality in AP is still a topic of interest [18, 19]. At this (such as fasting or the administration of parenteral nutri- point, the values of TG in relation to local and systemic tion), and analyze the role of TG levels as an early pre- complications and the severity of AP have not been clearly dictor of complications. Applying these criteria, we defined. Our study aimed to analyze the association of performed a subanalysis to determine whether the time elevated TG levels with complications and severity of AP. from the onset of symptoms to admission could be a con- founding factor, and we found no significant association with outcomes of acute pancreatitis. Materials and methods Management of AP Study design According to the international guidelines [20, 21], our A prospective single-cohort observational study of adult patients institutional management protocol of AP initially included diagnosed with AP in a third-level referral center was designed fluid therapy according to the patient characteristics with a to evaluate the role of elevated levels of TG in AP patients. goal of a urinary output of more than 0.5 ml/kg/hour, based on ringer lactate and isotonic sodium chloride solutions. No Inclusion criteria empirical antibiotics were used. When severe AP was suspected, the patient was referred to the ICU team for PatientsC18 years of age with AP were included according management and counseling. to the definitions of Atlanta 2012 [8]. The diagnosis of AP requires two of the following three features: (1) Typical Triglyceride determination and group division according to TG levels 1 Department of Hepato-Pancreato-Biliary and Transplant Serum TG levels were measured in the first 24 h after Surgery, Universitat Autonoma de Barcelona, Hospital admission by enzymatic techniques with spectrophoto- Universitari Vall d’Hebron, Passeig de la Vall d’Hebron, metric methods (Beckman Coulter Method). In our labo- 119-129, 08035 Barcelona, Spain ratory, the normal reference intervals are 43–200 mg/dL, 2 Department of Gastroenterology, Hospital Universitari Vall regardless of the sex and age of the patient. d’Hebron, Barcelona, Spain 123 World J Surg We divided the sample based on the classification of the score of 2 or more points for one of three organs (renal, National Cholesterol Education Program-Adult Treatment cardiovascular, or respiratory). Multiple organ failure Panel III (NCEP-ATP III) [22], in which patients with TG involves two or more organ systems, and persistent organ levelsC200 mg/dL are considered to have high TGs. We failure is defined as organ failure prolonged for 48 h or also generated ROC curves of TG values and AP outcomes more. to identify the best cutoff point (Youden’s index), and we SIRS is defined by the satisfaction of any two of the obtained values similar to the reference value. We divided following criteria: temperature[38 or\36 °C, heart the patients into two groups for our study: one with TG rate[90 beats/minute, respiratory rate[20 breaths/minute values\200 mg/dL and another with TGC200 mg/dL or partial pressure of CO2\32 mmHg, leucocyte (Supplementary Material Figures 1–5). count[12,000 or\4000/microliters or[10% immature forms or bands [24]. Variables analyzed Mortality was defined as a fatality event occurring during admission or up to 90 days after discharge. Demographic data, including age, sex, and body mass index (BMI), were collected from all patients in the study. Severity classification and scores Previous diseases such as diabetes mellitus, high blood pressure, cardiovascular disease (myocardial infarction, The classification of the severity of AP of the patients was heart failure, cardiac arrhythmia), chronic lung disease based on the 2012 revision of the Atlanta Classification [8], (obstructive or hypertensive pulmonary disease), and which is as follows: mild disease, moderately severe dis- chronic kidney disease were recorded. The risk of patients ease, and severe disease, according to the presence of organ according to the American Society of Anesthesiologists failure and multiorgan failure and local complications. (ASA) classification was also recorded. The radiological severity of AP was assessed using the We collected vital signs upon admission, complete classical CT severity index classification [25] and the blood counts, complete metabolic profiles, liver function modified CT severity index [26, 27]. The Acute Physiology test results, serum amylase levels, and serum TG levels. and Chronic Health Evaluation II (APACHE II) score [28] We also collected data on admission to the intensive was also calculated for each patient at admission. care unit (ICU), the length of total hospital stay, and mortality during admission or up to 90 days after Statistical analysis discharge. We performed the Chi-square test or Fisher’s exact test to Pancreatic or peripancreatic complications analyze qualitative variables. For normal distributions, the quantitative variables were compared by Student’s t test for Local complications evaluated were pancreatic and extra- two groups and skewed data, and the nonparametric test pancreatic necrosis, infection or necrosis, and the need for used was the Mann–Whitney U test. We performed mul- invasive procedures to treat necrosis. tivariable logistic regression to evaluate the association Pancreatic necrosis was defined as the absence of between TG levelsC200 mg/dL and other risk factors for enhancement in pancreatic tissue after contrast-enhanced each outcome of AP. A value of p\0.05 was considered CT or the presence of extrapancreatic fat necrosis. statistically significant. Statistical analysis was performed Infectious pancreatic necrosis (IPN) was defined as a using the commercial software SPSS version 20 (SPSS positive culture for microorganisms after necrosectomy or Inc., Chicago, Illinois). interventional (radiological or endoscopic) drainage. We also collected data on the need for an interventional radi- Ethics ological procedure, an endoscopic procedure, or surgical intervention. Following the Helsinki Declaration principles for human investigations, our local Ethical Committee approved the Systemic complications present study and the prospective database (PR-AG 328/2017). All participants signed informed consent to The systemic complications analyzed were respiratory participate in our prospective register. failure, cardiovascular failure, acute renal failure, organ failure, persistent organ failure, multiorgan failure and systemic inflammatory response syndrome (SIRS). Organ failure is the failure of an essential system in the body defined using the Marshall scoring system [23] as a 123 World J Surg Table 1 Demographic characteristics of acute pancreatitis according to TG levels group All cohort TG\200 mg/dL TGC200 mg/dL p N=247 N=200 N=47 Age, mean±SD 65.23±18.11 66.75±18.63 58.81±14.18 0.001 Male sex, N (%) 140 (56.7) 106 (53) 34 (72.3) 0.016 BMI Kg/m2, mean±SD 27.96±5.1 27.77±5.16 28.7±4.78 0.239 Previous Diseases, N (%) Diabetes 58 (23.5) 45 (22.5) 13 (27.7) 0.453 Higher blood pressure 141 (57.1) 115 (57.5) 26 (55.3) 0.786 Cardiovascular disease 61 (24.7) 52 (26) 9 (19.1) 0.327 Lung disease 38 (15.4) 29 (14.5) 9 (19.1) 0.427 Chronic kidney disease 23 (9.3) 21 (10.5) 2 (4.3) 0.266 Obesity 73 (30.5) 54 (27.7) 19 (43.2) 0.044 Dyslipidemia 84 (34) 63 (31.5) 21 (44.7) 0.086 Previous pancreatitis, N (%) 49 (25.7) 36 (23.2) 13 (36.1) 0.111 ASA (III, IV), N (%) 94 (38.1) 75 (37.5) 19 (40.4) 0.710 Pancreatitis etiology, N (%) \0.001 Biliary 143 (57.9) 126 (63) 17 (36.4) 0.001 Alcoholism 45 (18.2) 26 (13) 19 (40.4) \0.001 Idiopathics 39 (15.8) 32 (16) 7 (14.9) 0.852 Post-ERCP 8 (3.2) 6 (3) 2 (4.3) 0.650 Other 12 (4.9) 10 (5) 2 (4.3) 1 BMI body mass index, TG triglyceride, ASA American Society of Anesthesiologists classification, ERCP endoscopic retrograde cholan- giopancreatography, Others drugs, pancreas divisum, autoimmune, intraductal papillary mucinous neoplasm, post-surgical procedure Results Laboratory and APACHE-II scores From January 2016 to December 2019, a total of 350 Laboratory parameters on admission are described in patients with AP were diagnosed. We excluded nine Table 2. We found no differences between groups regard- transferred patients, 54 patients arriving to the emergency ing the APACHE score and other relevant laboratory department with more than 72 h from the onset of values. abdominal pain, three patients with HTG as a syndrome, and 37 patients in whom the determination of the TG level Local and systemic complications and severity was not possible. Finally, 247 patients were included in the study. All parameters regarding local and systemic complications, Two hundred out of 247 (81%) patients had CT severity indices, and severity of AP according to TGs\200 mg/dL, and 47 (19%) had TGsC200 mg/dL. The Atlanta definitions were worse in the TGC200 mg/dL mean TG levels were 111.24±36.88 mg/dL vs. group than in the TG\200 mg/dL group, except in IPN 339.68±177.88 for the TG\200 mg/dL group and (Table 3). TGC200 mg/dL group, respectively (p\0.001). We carried out an independent analysis according to sex The baseline characteristics of the entire cohort are lis- and found no differences in the association of TG ted in Table 1. No significant differences were found levels[200 mg/dL with the outcomes of AP observed in between groups regarding previous comorbidities, and our total population. ASA classification, except for age and sex. Biliary pancreatitis was the more frequent etiology in Hospital stay and mortality the TG\200 mg/dL group in comparison with the TG[200/dL group (63 vs. 36.4%, p\0.001); this was The need for admission to the ICU was higher in the opposite to alcoholic pancreatitis, which was the more TGC200 mg/dL group than in the group with TG\200 mg/ frequent etiology in the TGC200 mg/dL group compared dL (27.7 vs. 9.5%, p=0.001, OR: 3.64). with the TG\200 mg/dL group (40.3 vs. 13%, p\0.001). 123 World J Surg Table 2 Laboratory and APACHE score of acute pancreatitis according to TG levels group TG\200 mg/dL TGC200 mg/dL P N=200 N=47 Laboratory: Amylase U/L, mean±SD 1194.86±1763.83 772.81±938.55 0.114 Triglycerides mg/dL, mean±SD 111.24±36.88 339.68±177.88 \0.001 Leukocytes 103/mL, mean±SD 13,914.29±6066.5 15,154.26±5322.23 0.086 Hematocrit %, mean±SD 42.74±5.44 41.79±6.69 0.596 Platelets 103/mL, mean±SD 252.38±97.64 253.51±77.72 0.644 Creatinine mg/dL, mean±SD 1.03±0.49 1.15±0.58 0.159 BUN mg/dL 22.39±13.08 20.11±12.65 0.280 Bilirubin mg/dL, mean±SD 1.74±2.52 1.92±2.02 0.646 Alkaline phosphatase U/L, mean±SD 145.48±114.41 171.30±198.65 0.261 GGT mg/dL, mean±SD 261.83±363.68 588.02±685.33 0.004 AST U/L, mean±SD 202.78±274.74 186.02±327.16 0.717 ALT U/L, mean±SD 161.61±200.38 169.57±341.05 0.833 Albumin mg/dL, mean±SD 3.36±0.51 3.21±0.71 0.141 CRP mg/dL, mean±SD 5.43±7.74 8.78±11.11 0.069 APACHE II, mean±SD 7.02±3.82 6.85±3.51 0.791 TG triglyceride, BUN blood urea nitrogen, GGT gamma-glutamyl transpeptidase, AST aspartate aminotransferase, ALT alanine aminotransferase, CRP C-reactive protein, APACHE II Acute Physiology and Chronic Health Evaluation II score Table 3 Complications of acute pancreatitis according to TG levels group TG\200 mg/dL TGC200 mg/dL p OR (95% CI) N=200 N=47 Respiratory failure, N (%) 20 (10) 10 (21,3) 0.033 2.43 (1.05–5.62) Renal failure, N (%) 24 (12) 11 (23.4) 0.044 2.24 (1.01–4.98) Cardiovascular failure, N (%) 15 (7.5) 9 (19.1) 0.025 2.92 (1.19–7.16) Organ failure, N (%) 37 (18.5) 16 (34) 0.02 2.27 (1.13–4.58) Persistent organ failure, N (%) 19 (9.5) 13 (27.7) 0.001 3.64 (1.65–8.07) Multiple organ failure, N (%) 16 (8) 9 (19.1) 0.031 2.72 (1.12–6.62) Persistent multiple organ failure, N (%) 14 (7) 8 (17) 0.044 2.73 (1.07–6.94) SIRS, N (%) 70 (35%) 25 (53,2) 0.021 2.11 (1.11–4.01) Persistent SIRS, N (%) 44 (22.2) 17 (37.8) 0.043 2.01 (1.01–3.98) ATLANTA classification, N (%) \0.001 MAP 119 (59.5) 15 (31.9) MSAP 63 (31.5) 19 (40.4) SAP 18 (9) 13 (27.7) ATLANTA MSAP and SAP, N (%) 81 (40.5) 32 (68.1) 0.001 3.13 (1.59–6.16) Pancreatic necrosis, N (%) 68 (34) 30 (63.8) \0.001 3.43 (1.77–6.65) Pancreatic necrosis infection, N (%) 16 (23.5) 8 (26.7) 0.739 1.18 (0.44–3.16) Invasive procedure against necrosis, N (%) 19 (9.5) 12 (25.5) 0.003 3.27 (1.46–7.33) CT severity index, mean±SD 3.24±2.49 4.87±2.84 0.001 Modified CT severity index, mean±SD 4.94±2.82 6.15±3.09 0.022 Admission to ICU, N (%) 19 (9.5) 13 (27.7) 0.001 3.64 (1.65–8.07) Hospital length of stay (days), mean±SD 17.81±22.97 27.04±29.91 0.020 Mortality, N (%) 7 (3.5) 5 (10.6) 0.056 3.28 (0.99–10.85) TG triglyceride, SIRS systemic inflammatory response syndrome, ATLANTA Atlanta Classification of the severity, MAP mild acute pancreatitis, MSAP moderately severe acute pancreatitis, SAP severe acute pancreatitis, CT computed tomography, ICU intensive care unit *Invasive procedure against necrosis include interventional radiological procedure, endoscopic procedure, and surgical intervention 123 World J Surg The length of hospital stay was higher in the viscosity could also cause capillary ischemia of the pan- TGC200 mg/dL group (27.04±29.91 vs. 17.81±22.97, creatic parenchyma [40]. Other explanations could be p=0.02). related to the release of cytokines secondary to AP, espe- Mortality was higher in the TGC200 mg/dL group cially in necrotizing AP. Interleukin-6 is one of the most (10.6%) than in the TG\200 mg/dL group (3.5%), frequent cytokines in AP. Higher concentrations of IL-6 are although these differences were not statistically significant. related to severe forms of AP, worsening the clinical course of the disease [41]. Additionally, IL-6 plays a role in the Multivariable analysis for outcomes of AP release of triglycerides from hepatocytes through the cir- culation [42]. The release of higher cytokine concentrations In the multivariable logistic regression analysis to evaluate in severe AP could explain the early elevated TG levels and the association between TG levelsC200 mg/dL and other the consequently higher incidence of complications in this risk factors for each outcome of AP, we found that TG group of patients. levelsC200 mg/dL were independently associated with Additionally, the extravasation of FFA through the respiratory failure (OR: 3.37), renal failure (OR: 3.56), alveolar-capillary membrane may explain the lung injury in cardiovascular failure (OR: 3.03), organ failure (OR: 3.56), AP patients with elevated TG levels [43, 44]. Our study persistent organ failure (OR: 4.65), multiple organ failure showed that respiratory failure and cardiovascular failure (OR: 2.83), pancreatic necrosis (OR: 2.92), severe pan- were higher in patients with a high TG level at admission. creatitis (OR: 4.25), and admission to the ICU (OR: 3.57), Elevated TG levels have also been described as an as shown in Table 4. We did not find an association independent risk factor for the development of acute renal between TG levelsC200 mg/dL and IPN or mortality. failure in patients with AP [45], probably explained by the fact that the triglycerides deposited around the renal tubules will react with pancreatic lipase, which can directly Discussion damage the renal parenchyma and produce a high level of free fatty acids around the renal cells [46]. In our study, Our study observed that patients with TG levelsC200 mg/ patients in the TGC200 mg/dL group had a higher inci- dL measured in the first 24 h after admission for AP had a dence of acute renal failure. worse clinical outcome. Serum TG levelsC200 mg/dL Elevated TG levels have been described as an inde- were associated with respiratory failure, cardiovascular pendent predictor of pancreatic necrosis [47], and they are failure, organ failure, persistent organ failure, multiple also related to the extension of parenchymal necrosis [35]. organ failure, pancreatic necrosis, pancreatitis severity, and We found similar results in our cohort regarding the rela- admission to the ICU. tionship with pancreatic parenchymal necrosis. However, The role of elevated TG levels in patients with non-HTG the findings were not the same for the occurrence of syndrome-induced AP is unknown. Some authors have infectious pancreatic necrosis (IPN) since its mechanism reported that elevated TG levels are related to severe forms involves other crucial risk factors, such as bacterial of acute necrotizing pancreatitis, concluding that elevated translocation from the intestinal tract, use of total par- TG levels are an independent factor for severe AP enteral nutrition, or extrapancreatic source of infections [15, 29–31]. However, other studies show no significant [48]. relationship between elevated TG levels and the severity of In our cohort, the TGC200 mg/dL group did not expe- AP, and one of the hypotheses is that elevated TG levels rience significant mortality compared with that in the represent only a secondary manifestation of AP [32–34]. TG\200 mg/dL group. One explanation relies on the low The mechanism explaining why elevated TG levels are mortality rate in our entire cohort, making it difficult to find related to severe AP is still unknown. However, several differences between groups. pathogenic theories have been proposed: in the early stages Identifying the mechanisms by which TG levels increase of AP, the release of serum catecholamines and glucagon, in acute pancreatitis and how they cause tissue damage will as well as pancreatic lipases, in response to stress accel- help develop new treatment strategies for severe forms of erates the decomposition of the adipose tissue with the AP. Studies carried out in AP induced by HTG suggest that consequent release of triglycerides as its degradation early removal of triglycerides and toxic free fatty acids products (free fatty acids, FFA) through the systemic cir- may be advantageous; however, high-quality evidence is culation [35]. It is well-known that excess FFA in the still missing in the literature [49–52]. circulation induces direct tissue damage [36–38], positive There are some limitations to our study. First, TG values regulation of cytokines, and activation of inflammatory were measured within 24 h after admission to the hospital; cascades that predispose to organ failure [39]. Furthermore, thus, the time between the onset of symptoms and serum under conditions of excess FFA, the plasma’s high TG measurement is not the same in all patients. However, 123 World J Surg Table 4 Univariate and multivariable analysis to evaluate the association between TG levelC200 mg/dL and other risk factors for each outcome of acute pancreatitis Univariate analysis Multivariable analysis OR (95% CI) p value OR (95% CI) p value Respiratory failure Age (C 65 years) 2.46 (1.01–5.99) 0.046 2.51 (0.9–7.01) 0.078 Higher blood pressure 2.76 (1.14–6.69) 0.025 2.03 (0.77–5.32) 0.151 TGs (C 200 mg/dL) 2.43 (1.05–5.62) 0.038 3.37 (1.35–8.43) 0.009 Renal failure Diabetes 2.95 (1.39–6.23) 0.005 1.87 (0.82–4.25) 0.135 Higher blood pressure 2.9 (1.26–6.68) 0.012 1.85 (0.73–4.65) 0.194 Cardiovascular disease 2.34 (1.11–4.95) 0.026 1.53 (0.64–3.73) 0.34 Chronic kidney disease 4.89 (1.93–12.43) 0.001 2.79 (0.93–8.37) 0.067 Biliary etiology 2.79 (1.21–6.43) 0.016 2.43 (0.95–6.25) 0.065 TGs (C 200 mg/dL) 2.24 (1.01–4.98) 0.048 3.56 (1.43–8.86) 0.006 Cardiovascular failure Diabetes 3.17 (1.33–7.52) 0.009 2.52 (1.02–6.19) 0.044 Higher blood pressure 3.15 (1.14–8.72) 0.028 2.74 (0.95–7.89) 0.062 TGs (C 200 mg/dL) 2.92 (1.19–7.16) 0.019 3.03 (1.19–7.66) 0.02 Organ failure Diabetes 2.49 (1.29–4.81) 0.007 1.62 (0.78–3.33) 0.193 Higher blood pressure 3.21 (1.59–6.48) 0.001 2.28 (1.06–4.89) 0.035 Cardiovascular disease 2.02 (1.05–3.9) 0.036 1.49 (0.7–3.2) 0.297 Chronic kidney disease 3.24 (1.33–7.88) 0.01 1.71 (0.61–4.77) 0.304 Biliary etiology 2.72 (1.37–5.4) 0.004 2.65 (1.21–5.8) 0.015 TGs (C 200 mg/dL) 2.27 (1.13–4.58) 0.022 3.56 (1.59–7.98) 0.002 Persistent organ failure Diabetes 3.02 (1.39–6.55) 0.005 2.11 (0.91–4.88) 0.08 Higher blood pressure 3.05 (1.26–7.35) 0.013 2.61 (1.01–6.75) 0.048 Chronic kidney disease 3.48 (1.31–9.29) 0.013 3.24 (1.12–9.38) 0.03 TGs (C 200 mg/dL) 3.64 (1.65–8.07) 0.001 4.65 (1.96–11.03) \0.001 Multiple organ failure Diabetes 3.53 (1.51–8.26) 0.004 2.8 (1.16–6.76) 0.022 Higher blood pressure 3.34 (1.21–9.21) 0.02 2.83 (0.99–8.13) 0.053 TGs (C 200 mg/dL) 2.72 (1.12–6.62) 0.027 2.83 (1.12–7.13) 0.028 Pancreatic necrosis Sex Male 4.21 (2.38–7.44) \0.001 3.85 (2.11–7.01) \0.001 Alcohol etiology 2.21 (1.15–4.25) 0.018 1.05 (0.5–2.19) 0.894 TGs (C 200 mg/dL) 3.43 (1.77–6.65) \0.001 2.92 (1.43–5.96) 0.003 ATLANTA Severe AP Diabetes 2.74 (1.25–6.02) 0.012 2.21 (0.96–5.09) 0.062 Higher blood pressure 2.39 (1.02–5.58) 0.044 2.09 (0.85–5.19) 0.109 Cardiovascular disease 3.65 (1.36–9.75) 0.01 1.47 (0.62–3.52) 0.382 TGs (C 200 mg/dL) 3.13 (1.59–6.16) 0.001 4.25 (1.83–9.87) 0.001 Admission to ICU Diabetes 2.2 (1.01–4.84) 0.049 2.14 (0.95–4.79) 0.065 TGs (C 200 mg/dL) 3.64 (1.65–8.07) 0.001 3.57 (1.59–7.97) 0.002 ATLANTA Atlanta Classification of the severity, AP acute pancreatitis, ICU intensive care unit, TG triglycerides, OR: odds ratio, CI confidence interval 123 World J Surg to diminish bias, we selected patients with no more than holder. To view a copy of this licence, visit http://creativecommons. 72 h from the onset of symptoms until admission. Second, org/licenses/by/4.0/. the TG values of the patients before the AP episode were not available, which could have influenced the values obtained on admission, making it difficult to discern References whether the TG levels were a consequence of the AP or a secondary, previous conditioning disease. Third, the fact 1. Wu BU, Conwell DL (2010) Update in acute pancreatitis. Curr that the basal characteristics of both groups differed in sex, Gastroenterol Rep 12(2):83–90 alcohol etiology, and BMI could be a source of bias 2. Tenner S, Baillie J, DeWitt J et al (2013) American college of regarding the higher incidence of complications in this type gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 108(9):1400–1415 of patient. For this reason, we performed a multivariable 3. 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Departments of Surgery up approach or open necrosectomy for necrotizing pancreatitis. and Morphological Science at the Universitat Autònoma. N Engl J Med 362(16):1491–1502 11. van Brunschot S, Hollemans RA, Bakker OJ et al (2018) Mini- Funding Open Access Funding provided by Universitat Autonoma mally invasive and endoscopic versus open necrosectomy for de Barcelona. necrotising pancreatitis: a pooled analysis of individual data for 1980 patients. Gut 67(4):697–706 Declarations 12. Ismailov US, Aripova NU, Alidjanov FB et al (2009) The role of endoscopic sphincterotomy in the management of acute biliary Conflict of interest The authors declare that they have no conflict of pancreatitis. In: Iovanna J, Ismailov U (eds) Pancreatology. interest. Springer, Berlin, pp 77–85 13. Waldthaler A, Schutte K, Malfertheiner P (2010) Causes and Ethical approval Sex-Inclusive SJEG Guidelines: Our study mechanisms in acute pancreatitis. Dig Dis 28(2):364–372 includes male and female sex. 14. 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BMC Gastroenterol 15:19 jurisdictional claims in published maps and institutional affiliations. 123 World J Surg Nils Jimmy Hidalgo was born Pancreato-Biliary and Transplant Surgery at Hospital Universitari and raised in Peru. He obtained Vall d’Hebron. He is currently doing Doctoral Studies at the his medical degree from the Autonomous University of Barcelona. Universidad Nacional Mayor de San Marcos. He immigrated to Spain and completed his surgi- cal residency training at Hospi- tal Clinico de Barcelona. He completed his training with a Master’s Degree in Donation and Transplantation and a Mas- ter’s Degree in Design and Analysis of Clinical Research from the University of Barce- lona. His research has focused on pancreatic pathology as part of the Department of Hepato- 123