Involvement of transverse mesocolon is associated with development of colonic fistula in patients with acute necrotizing pancreatitis.

BACKGROUND: Involvement of transverse mesocolon (TM) during acute necrotizing pancreatitis(ANP) indicates that inflammation has spread from retroperitoneal space to peritoneum. Nevertheless, the impact of TM involvement, as confirmed by contrast-enhanced computed tomography (CECT), on local complications and clinical outcomes was poorly investigated. PURPOSE: This study aimed to explore the association between CECT-diagnosed TM involvement and the development of colonic fistula in a cohort of ANP patients. METHODS: This is a single-center, retrospective cohort study involving ANP patients admitted from January 2020 to December 2020. TM involvement was diagnosed by two experienced radiologists. The study subjects were enrolled consecutively and divided into two groups: TM involvement and non-TM involvement. The primary outcome was colonic fistula during the index admission. Clinical outcomes were compared between the two groups, and the association between the TM involvement and the development of colonic fistula was assessed using multivariable analysis to adjust for baseline unbalances. RESULTS: A total of 180 patients with ANP were enrolled, and 86 (47.8%) patients had TM involvement. The incidence of the colonic fistula is significantly higher in patients with TM involvement (16.3% vs. 5.3%;p = 0.017). Moreover, the length of hospital stay was 24(13,68) days in patients with TM involvement and 15(7,31) days in those not (p = 0.001). Analysis of multivariable logistic regression revealed that TM involvement is an independent risk factor for the development of colonic fistula (odds ratio: 10.253, 95% CI: 2.206-47.650, p = 0.003). CONCLUSION: TM involvement in ANP patients is associated with development of colonic fistula in ANP patients.

Early versus delayed intervention in necrotizing acute pancreatitis complicated by persistent organ failure.

BACKGROUND: Current guidelines for the treatment of patients with necrotizing acute pancreatitis (NAP) recommend that invasive intervention for pancreatic necrosis should be deferred to 4 or more weeks from disease onset to allow necrotic collections becoming "walled-off". However, for patients showing signs of clinical deterioration, especially those with persistent organ failure (POF), it is controversial whether this delayed approach should always be adopted. In this study, we aimed to assess the impact of differently timed intervention on clinical outcomes in a group of NAP patients complicated by POF. METHODS: All NAP patients admitted to our hospital from January 2013 to December 2017 were screened for potential inclusion. They were divided into two groups based on the timing of initial intervention (within 4 weeks and beyond 4 weeks). All the data were extracted from a prospectively collected database. RESULTS: Overall, 131 patients were included for analysis. Among them, 100 (76.3%) patients were intervened within 4 weeks and 31 (23.7%) underwent delayed interventions. As for organ failure prior to intervention, the incidences of respiratory failure, renal failure and cardiovascular failure were not significantly different between the two groups (P > 0.05). The mortality was not significantly different between the two groups (35.0% vs. 32.3%, P = 0.83). The incidences of new-onset multiple organ failure (8.0% vs. 6.5%, P = 1.00), gastrointestinal fistula (29.0% vs. 12.9%, P = 0.10) and bleeding (35.0% vs. 35.5%, P = 1.00), and length of ICU (30.0 vs. 22.0 days, P = 0.61) and hospital stay (42.5 vs. 40.0 days, P = 0.96) were comparable between the two groups. CONCLUSION: Intervention within 4 weeks did not worsen the clinical outcomes in NAP patients complicated by POF.

Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG. OBJECTIVES: The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older sister). METHODS: The entire coding and flanking sequences of LPL, APOC2, APOA5, GPIHBP1 and LMF1 genes were analyzed by Sanger sequencing. The newly identified LPL nonsense variant was subjected to functional analysis by means of transfection into HEK-293 T cells followed by Western blot and activity assays. Previously reported pathogenic LPL nonsense variants were collated and compared with respect to genotype and phenotype relationship. RESULTS: We identified a novel nonsense variant, p.Gln118* (c.351C > T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. We provided in vitro evidence that this variant resulted in a complete functional loss of the affected LPL allele. We highlighted a role of alcohol abuse in modifying the clinical expression of the disease in the proband. Additionally, our survey of 12 previously reported pathogenic LPL nonsense variants (in 20 carriers) revealed that neither serum triglyceride levels nor occurrence of HTG-AP was distinguishable among the three carrier groups, namely, simple homozygotes, compound heterozygotes and simple heterozygotes. CONCLUSIONS: Our findings, taken together, generated new insights into the complex etiology and expression of HTG-AP.

Management of colonic fistulas in patients with infected pancreatic necrosis being treated with a step-up approach.

BACKGROUND: Colonic fistula is a potentially fatal complication in acute necrotizing pancreatitis (ANP), especially in patients with infected pancreatic necrosis (IPN). The aim of this study was to evaluate the feasibility of a step-up approach including percutaneous catheter drainage (PCD) and continuous negative pressure irrigation (CNPI) in a group of patients with colonic fistula. METHODS: A retrospective review of a prospectively collected data was performed. Data were extracted for patients complicated by colonic fistula from January 2010 to January 2017. RESULTS: A total of 1750 patients were admitted with ANP during the study period. Of these patients, 711 (41%) developed IPN and colonic fistula was present in 132 (19%). A step-up approach was adopted for all patients, with 47% avoiding surgery. The mortality in patients requiring surgery (37%) was higher than that in patients managed non-surgically (19%) constituting an overall mortality rate of 29%. In patients managed conservatively, 92% had spontaneous closure of the fistula. CONCLUSION: Colonic fistula is not a rare complication in ANP occurring in 19% of patients with IPN in the current study. A step-up approach was effective and safe in managing colonic fistula and surgery could be obviated in nearly half of the patients.

Identification of a novel and heterozygous LMF1 nonsense mutation in an acute pancreatitis patient with severe hypertriglyceridemia, severe obesity and heavy smoking.

BACKGROUND: Hypertriglyceridemia (HTG) is one of the most common etiologies of acute pancreatitis (AP). Variants in five genes involved in the regulation of plasma lipid metabolism, namely LPL, APOA5, APOC2, GPIHBP1 and LMF1, have been frequently reported to cause or predispose to HTG. METHODS: A Han Chinese patient with HTG-induced AP was assessed for genetic variants by Sanger sequencing of the entire coding and flanking sequences of the above five genes. RESULTS: The patient was a 32-year-old man with severe obesity (Body Mass Index = 35) and heavy smoking (ten cigarettes per day for more than ten years). At the onset of AP, his serum triglyceride concentration was elevated to 1450.52 mg/dL. We sequenced the entire coding and flanking sequences of the LPL, APOC2, APOA5, GBIHBP1 and LMF1 genes in the patient. We found no putative deleterious variants, with the exception of a novel and heterozygous nonsense variant, c.1024C > T (p.Arg342*; rs776584760), in exon 7 of the LMF1 gene. CONCLUSIONS: This is the first time that a heterozygous LMF1 nonsense variant was found in a HTG-AP patient with severe obesity and heavy smoking, highlighting an important interplay between genetic and lifestyle factors in the etiology of HTG.

Intercostal artery damage and massive hemothorax after thoracocentesis by central venous catheter: A case report.

Central venous catheters (CVCs) are widely used in various puncture and drainage operations in intensive care units (ICUs) in recent years. Compared to conventional operating devices, CVC was welcomed by clinicians because of the advantages of easy use, less damage to the body and convenient fixation process. We came across a patient with severe acute pancreatitis (SAP) who developed cardiac arrest due to thoracic cavity massive bleeding 24 h after thoracocentesis with CVC. Thoracotomy surgery was carried out immediately, which confirmed an intercostal artery injury. The patient was discharged from hospital without any neurological complications two months later. Here we report this case to remind all the emergency department and ICU physicians to pay more attention to the complication of thoracic cavity bleeding following thoracocentesis conducted by CVC.

Early enteral nutrition prevents intra-abdominal hypertension and reduces the severity of severe acute pancreatitis compared with delayed enteral nutrition: a prospective pilot study.

BACKGROUND: To investigate the effects of early enteral nutrition (EEN) on intra-abdominal pressure (IAP) and disease severity in patients with severe acute pancreatitis (SAP). METHODS: Enteral nutrition (EN) was started within 48 h after admission in the EEN group and from the 8th day in the delayed enteral nutrition (DEN) group. The IAP and intra-abdominal hypertension (IAH) incidence were recorded for 2 weeks. The caloric intake and feeding intolerance (FI) incidence were recorded daily after EN was started. The severity markers and clinical outcome variables were also recorded. RESULTS: Sixty patients were enrolled to this study. No difference about IAP was found. The IAH incidence of the EEN group was significantly lower than that of the DEN group from the 9th day (8/30 versus 18/30; P = 0.009) after admission. The FI incidence of the EEN group was higher than that of the DEN group during the initial 3 days of feeding (25/30 versus 12/30; P = 0.001; 22/30 versus 9/30; P = 0.001; 15/30 versus 4/30; P = 0.002). Patients with an IAP <15 mmHg had lower FI incidence than those with an IAP ≥15 mmHg on the 1st day (20/22 versus 17/38; P < 0.001), the 3rd day (11/13 versus 8/47; P < 0.001), and the 7th day (3/5 versus 3/55; P = 0.005) of feeding. The severity markers and clinical outcome variables of the EEN group were significantly improved. CONCLUSIONS: Early enteral nutrition did not increase IAP. In contrast, it might prevent the development of IAH. In addition, EEN might be not appropriate during the initial 3-4 days of SAP onset. Moreover, EN might be of benefit to patients with an IAP <15 mmHg. Early enteral nutrition could improve disease severity and clinical outcome, but did not decrease mortality of SAP.

Modified gastrointestinal failure score for patients with severe acute pancreatitis.

PURPOSE: No consensus has been reached to define gastrointestinal failure (GIF) associated with severe acute pancreatitis (SAP). Reintam and colleagues proposed a scoring system of GIF for critically ill patients, but its suitability for patients with SAP is questionable. The present study evaluates a modified GIF score we developed to assess the GIF of patients with SAP. METHODS: The subjects of this study were 52 patients with SAP treated between September 2010 and July 2011. We recorded the Reintam's GIF score, our modified GIF score, the acute physiology and chronic health evaluation (APACHE) II score, the sequential organ failure assessment (SOFA) score, and other clinical values during the first 3 days after admission. The prognostic value of the modified GIF score, for evaluating the severity and outcomes of SAP, was also assessed. RESULTS: Compared with the Reintam's GIF score, the modified GIF score seemed to be more valuable for predicting hospital mortality (the area under curve, AUC 0.915 vs. 0.850), multiple organ dysfunction syndrome (MODS) (AUC 0.829 vs. 0.766), and pancreatic infection (AUC 0.796 vs. 0.776). Moreover, combining the modified GIF score and the SOFA or APACHEII scores resulted in more accurate prediction of the prognosis of SAP than either score alone. CONCLUSION: The modified GIF score is useful for assessing gastrointestinal system function, which may serve as an early prognostic tool to evaluate the severity and predict the outcomes of SAP.

Association of demographic and clinical factors with risk of acute pancreatitis: An exposure-wide Mendelian randomization study.

BACKGROUND: The incidence of acute pancreatitis (AP) is increasing over years, which brings enormous economy and health burden. However, the aetiologies of AP and underlying mechanisms are still unclear. Here, we performed a two-sample Mendelian randomization (MR) analysis to investigate the associations between all reported possible risk factors and AP using publicly available genome-wide association study summary statistics. METHODS: A series of quality control steps were taken in our analysis to select eligible instrumental single nucleotide polymorphisms which were strongly associated with exposures. To make the conclusions more robust and reliable, we utilized several analytical methods (inverse-variance weighting, MR-PRESSO method, weighted median, MR-Egger regression) that are based on different assumptions of two-sample MR analysis. The MR-Egger intercept test, radial regression and leave-one-out sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on each exposure. A two-step MR method was applied to explore mediators in significant associations. RESULTS: Genetic predisposition to cholelithiasis (effect estimate: 17.30, 95% CI: 12.25-22.36, p = 1.95 E-11), body mass index (0.32, 95% CI: 0.13-0.51, p < 0.001), body fat percentage (0.57, 95% CI: 0.31-0.83, p = 1.31 E-05), trunk fat percentage (0.36, 95% CI: 0.14-0.59, p < 0.005), ever smoked (1.61, 95% CI: 0.45-2.77, p = 0.007), and limbs fat percentage (0.55, 95% CI: 0.41-0.69, p < 0.001) were associated with an increased risk of AP. In addition, whole-body fat-free mass (-0.32, 95% CI: -0.55 to -0.10, p = 0.004) was associated with a decrease risk of AP. CONCLUSION: Genetic predisposition to cholelithiasis, obesity and smoking could be causally associated with an increased risk of AP, and whole body fat-free mass could be associated with a decreased risk of AP.

Risk factors and outcome of intra-abdominal hypertension in patients with severe acute pancreatitis.

BACKGROUND: Intra-abdominal hypertension (IAH) is common in patients with severe acute pancreatitis (SAP). The aim of the present study was to investigate the risk factors of IAH in SAP patients and assess the prognosis of SAP combined with IAH. METHODS: To analyze the data from patients with SAP, both univariate and multivariate logistic regression analyses were applied, using 16 indices, including age, gender, Acute Physiology and Chronic Health Evaluation II scores (APACHE II), 24 h fluid balance, hematocrit, serum calcium level, and so on. Clinical prognosis such as mortality, hospital duration, of SAP patients with or without IAH was also compared. RESULTS: First 24 h fluid balance (Odds Ratio [OR], 1.003; 95% Confidence Interval [CI], 1.001-1.006), number of fluid collections (OR, 1.652; 95% CI, 1.023-2.956), and serum calcium level (OR, 0.132; 95% CI, 0.012-0.775) were found to be independent risk factors for IAH in patients with SAP. Moreover, patients with SAP and IAH had significantly longer average length of stay, both in the hospital and in the intensive care unit, higher rates of systemic and local complications, and more invasive treatments. CONCLUSIONS: The significant risk factors for IAH in patients with SAP include 24 h fluid balance (first day), number of fluid collections, and serum calcium level. Additionally, IAH is associated with extremely poor prognosis, evidenced by high rates of mortality, morbidity, and the need for invasive interventions.

[The immunomodulatory effects of hypertonic saline on sepsis patients].

OBJECTIVE: To approach the immunomodulatory effects of hypertonic saline (HTS) on sepsis patients. METHODS: Twenty-four septic patients admitted to surgical intensive care unit (SICU) received 5% HTS for fluid resuscitation were prospectively enrolled from January 2009 to September 2010. Blood samples were collected at 15 minutes before, and at 15 minutes and 6, 12, and 24 hours after HTS infusion, the ability of respiratory burst of polymorphonuclear neutrophils (PMN) and the surface expression of CD11b and L-selectin in fresh whole blood was evaluated with flow cytometer. The plasma was collected to determine the solubility intercellular adhesion molecule-1 (sICAM-1), solubility L-selectin (sL-selectin), tumor necrosis factor-α(TNF-α) and interleukins (IL-6, IL-1ß). RESULTS: The baseline before HTS infusion was set as 100. Six hours after HTS infusion, the ability of respiratory burst of PMN was significantly increased [(160.0±19.6)%] compared with the baseline (P<0.05), and then gradually recovered to normal level. The expression of CD11b and L-selectin in the surface of PMN was reduced rapidly at 15 minutes after HTS infusion, and to nadir at 12 hours [(70.4±5.7)%, (70.6±8.1)%], and L-selectin recovered to the normal level at 24 hours. Within short-term of HTS infusion, plasma inflammatory factor TNF-α was significantly decreased, and sustained a low level until 12 hours, and then gradually increased. There was no change in IL-1ß. IL-6 and sICAM-1 was gradually increased, and peaked at 24 hours and 12 hours respectively, and remained at a high level. sL-selectin increased shortly at 15 minutes after HTS infusion compared with baseline, and remained the level to 12 hours, and recovered to baseline at 24 hours. CONCLUSIONS: Delayed administration of HTS may have an immunomodulatory effect on sepsis patients, which could inhibit the activation of PMN.

[The effect of intra-abdominal hypertension on hemodynamics of acute necrotizing pancreatitis in porcine model].

OBJECTIVE: To assess the effect of intra-abdominal hypertension (IAH) on hemodynamics of severe acute pancreatitis (SAP) in porcine model. METHODS: Following baseline registrations, SAP was induced in 12 animals. The N(2) pneumoperitoneum was used to increase the intra-abdominal pressure to 30 mmHg (1 mmHg = 0.133 kPa) in 6 of 12 SAP animals thereafter and keep constant during the experiment. The investigation period was 12 h. Heart rate, cardiac output (CO), central venous pressure (CVP), mean arterial pressure and pulmonary arterial wedge pressure (PAWP) were continuously measured with the aid of balloon tipped flow-directed catheter and electrocardiography monitor. Oxygen partial pressure of artery (PaO(2)), carbon dioxide partial pressure of artery (PaCO(2)), ScvO(2), base excess (BE), and blood lactic acid (LAC) were measured by acid-base analysis. RESULTS: In the IAH group, CO decreased significantly at 12 h, CVP and PAWP increased significantly at 3 h, 6 h and 12 h compared with SAP group (all P < 0.05). Peak inspiration pressure increased immediately after pneumoperitoneum in the IAH group, to (50.2 ± 3.1) cmH(2)O (1 cmH(2)O = 0.098 kPa) and (49.8 ± 0.9) cmH(2)O at 6 h and 12 h respectively. The pH, PaO(2), ScvO(2) and BE showed a tendency to fall in the IAH group. PaCO(2) and LAC were increased significantly in the IAH group (all P < 0.05). CONCLUSIONS: There were remarkable and relatively irreversible effects on global hemodynamics in response to sustained IAH of 12 h with the underlying condition of SAP. Abdominal decompression is beneficial for patients of SAP with IAH.

[Effect of decompression in different time on hemodynamics and oxygen metabolism of porcine model with severe acute pancreatitis combined intra-abdominal hypertension].

OBJECTIVE: To assess the effect of decompression in different time on systemic hemodynamics and oxygen metabolism in a 24 h lasting porcine model of severe acute pancreatitis (SAP) incorporating intra-abdominal hypertension (IAH). METHODS: Following baseline registrations, SAP was induced in all 18 animals. A N(2) pneumoperitoneum was used to increase the intra-abdominal pressure (IAP) to 25 mmHg (1 mmHg = 0.133 kPa) in 12 of 18 SAP animals. After 6 hours, decompression was applied in 6 of these 12 pigs and the other 6 animals received decompression at 9 h since the induction of IAH. The investigation period was 24 h. Heart rate (HR), cardiac output (CO), central venous pressure (CVP), mean arterial pressure (MAP) and pulmonary arterial wedge pressure (PAWP) were continuously recorded with the aid of Swan-Ganz catheter and electrocardiography monitor; Oxygen partial pressure of artery (PaO(2)), carbon dioxide partial pressure of artery (PaCO(2)) and central venous oxygen saturation (ScvO(2)) were measured by blood-gas analysis. Besides that, systemic oxygen delivery (DO(2)) and systemic oxygen consumption (VO(2)) were calculated according to blood-gas analysis in arterial and central venous blood. RESULTS: After decompression, HR, CO, MAP, CVP, PAWP, PaO(2) and DO(2) showed no significant differences in the 6 h group when compared to SAP pigs. In the 9 h group, however, CO decreased significantly and HR, CVP, PAWP increased significantly after decompression than SAP only animals (all P < 0.05). PaO(2), ScvO(2) and DO(2) showed lower after 3 h of decompression compared with another two groups. VO(2) increased higher in IAH groups during 6 h of experiment than SAP pigs (all P < 0.05). Then VO(2) showed a trend to fall and no differences in three groups. CONCLUSIONS: There are remarkable and relatively irreversible effects on global hemodynamics and oxygen metabolism in response to the decompression in different time after sustained IAH with the underlying condition of SAP. The results of this study are in favor of a decompression in patients of SAP with IAH in early time.

[Effect of mechanical ventilation guided by transpulmonary pressure on hemodynamics and oxygen metabolism of porcine model of intra-abdominal hypertension].

OBJECTIVE: To assess the effect of mechanical ventilation (MV) guided by transpulmonary pressure (Ptp) on hemodynamics and oxygen metabolism of porcine model of intra-abdominal hypertension (IAH). METHODS: All 6 pigs were anesthetized and received MV. Volume-assist control was set: tidal volume (V(T)) was 10 ml/kg, respiratory rate (RR) was 16 bpm, inhaled oxygen concentration (FiO(2)) was 0.40 and positive end-expiratory pressure (PEEP) was set at 5 cm H(2)O (1 cm H(2)O=0.098 kPa). Following baseline observations, high intra-abdominal pressure (IAP) with intraperitoneal nitrogen inflation was induced in all 6 pigs. The IAP was increased to 25 mm Hg (1 mm Hg=0.133 kPa). Two hours later, PEEP was adjusted to such a level that Ptp during end-expiratory occlusion remained at a level above 0 cm H(2)O for 2 hours by measuring esophageal pressure, and with the rest parameters of breathing machine remaining constant. During the experimental period, hemodynamic parameters including heart rate (HR), mean arterial pressure (MAP), cardiac output index (CI), central venous pressure (CVP), pulmonary arterial wedge pressure (PAWP), and respiratory mechanics index of peak airway pressure (Ppeak), plateau pressure (Pplat), esophageal pressure (Pes) and static compliance (Cst) were continuously recorded with the aid of Swan-Ganz catheter and electrocardiogram. Oxygen partial pressure of arterial blood (PaO(2) ) and carbon dioxide partial pressure of arterial blood (PaCO(2)) were measured by blood-gas analysis. Systemic oxygen delivery (DO(2) )and systemic oxygen consumption(VO(2) )were calculated according to blood-gas analysis of arterial and central venous blood. RESULTS: No porcine model showed barotrauma and death. Compared with baseline, at 1 hour and 2 hours after induction of IAH in the animals, HR(bpm) increased significantly (134.3±5.8, 127.3±3.3 vs. 117.7±1.5). MAP(mm Hg), CVP (mm Hg) and PAWP (mm Hg) became higher (MAP:120.7±3.8, 117.3±4.8 vs. 100.4±6.6; CVP: 7.3±0.3, 7.6±0.9 vs. 5.6±0.2; PAWP: 14.0±0.6, 14.0±1.0 vs. 12.3±0.3), CI (L×min(-1)×kg(-1)) was lowered (0.150±0.019, 0.137±0.014 vs. 0.179±0.021), Ppeak(cm H(2)O), Pplat (cm H(2)O), Pes (cm H(2)O) were increased significantly (Ppeak: 46.3±2.3, 47.0±3.2 vs. 11.0±1.6; Pplat: 25.7±1.3, 26.0±1.6 vs. 9.0±0.6; Pes: 13.7±0.3, 14.3±0.3 vs. 2.3±0.3), Cst (ml/cm H(2)O), PaO(2) (mm Hg) and DO(2) (ml×min(-1)×kg(-1)) showed significant lowering (Cst: 8.3±0.3, 9.0±0.6 vs. 23.0±1.6; PaO(2) : 142.0±13.2, 140.0±16.0 vs. 166.3±11.3; DO(2) : 19.40±2.90, 19.88 ±4.14 vs. 25.07±6.30, all P<0.05).However, compared to routine ventilation, at 1 hour and 2 hours after PEEP had been adjusted according to measurements of esophageal pressure, PaO(2) , DO(2) and Cst increased significantly (PaO(2) : 161.6±11.9, 164.0±13.6; DO(2) : 21.90±6.21, 21.16±2.78; Cst: 12.0±1.6, 12.7±2.9). CI became lower (0.121±0.013, 0.120±0.012)and Pplat was higher(31.3±3.4, 31.7±3.2, all P<0.05). The lactate (mmol/L) was also decreased significantly (1.60±0.12 vs. 2.70±0.44, 1.67±0.07 vs. 2.27±0.13, both P<0.05). PaCO(2), HR, MAP, CVP and PAWP showed no significant differences compared to IAH pigs ventilated with lower PEEP (all P>0.05). CONCLUSION: There were remarkable effects on oxygen metabolism and Cst and less influence on hemodynamics in response to MV guided by Ptp. The results of this study are in favor of setting Ptp according to measurements of esophageal pressure in pigs with IAH.

Serum magnesium level as a predictor of acute kidney injury in patients with acute pancreatitis.

BACKGROUND: Decreased serum magnesium (Mg2+) is commonly seen in critically ill patients. Hypomagnesemia is significantly more frequent in patients with severe acute pancreatitis. Acute kidney injury (AKI) in patients with acute pancreatitis (AP) is associated with an extremely high mortality. The association underlying serum Mg2+ and AKI in AP has not been elucidated. AIM: To explore the association between serum Mg2+ on admission and AKI in patients with AP. METHODS: A retrospective observational study was conducted in a cohort of patients (n = 233) with AP without any renal injury before admission to our center from August 2015 to February 2019. Demographic characteristics on admission, severity score, laboratory values and in-hospital mortality were compared between patients with and without AKI. RESULTS: A total of 233 patients were included for analysis, including 85 with AKI. Compared to patients without AKI, serum Mg2+ level was significantly lower in patients with AKI at admission [OR = 6.070, 95%CI: 3.374-10.921, P < 0.001]. Multivariate logistic analysis showed that lower serum Mg2+ was an independent risk factor for AKI [OR = 8.47, 95%CI: 3.02-23.72, P < 0.001]. CONCLUSION: Our analysis indicates that serum Mg2+ level at admission is independently associated with the development of AKI in patients with AP and may be a potential prognostic factor.

Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis.

The etiology of hypertriglyceridemia (HTG) and acute pancreatitis (AP) is complex. Herein, we dissected the underlying etiology in a patient with HTG and AP. The patient had a 20-year history of heavy alcohol consumption and an 8-year history of mild HTG. He was hospitalized for alcohol-triggered AP, with a plasma triglyceride (TG) level up to 21.4 mmol/L. A temporary rise in post-heparin LPL concentration (1.5-2.5 times of controls) was noted during the early days of AP whilst LPL activity was consistently low (50∼70% of controls). His TG level rapidly decreased to normal in response to treatment, and remained normal to borderline high during a ∼3-year follow-up period during which he had abstained completely from alcohol. Sequencing of the five primary HTG genes (i.e., LPL, APOC2, APOA5, GPIHBP1 and LMF1) identified two heterozygous variants. One was the common APOA5 c.553G > T (p.Gly185Cys) variant, which has been previously associated with altered TG levels as well as HTG-induced acute pancreatitis (HTG-AP). The other was a rare variant in the LPL gene, c.756T > G (p.Ile252Met), which was predicted to be likely pathogenic and found experimentally to cause a 40% loss of LPL activity without affecting either protein synthesis or secretion. We provide evidence that both a gene-gene interaction (between the common APOA5 variant and the rare LPL variant) and a gene-environment interaction (between alcohol and digenic inheritance) might have contributed to the development of mild HTG and alcohol-triggered AP in the patient, thereby improving our understanding of the complex etiology of HTG and HTG-AP.

[Effect of liquid resuscitation on homeostasis of patients with severe acute pancreatitis].

OBJECTIVE: To evaluate the effect of liquid resuscitation on acid-base balance and electrolytes of patients with severe acute pancreatitis (SAP). METHODS: According to the target of liquid resuscitation, 22 patients with SAP involved in this self-controlled prospective study received sufficient liquid resuscitation in acute stage of acute pancreatitis. The results of blood gas analysis, acid-base balance and electrolytes were compared before and after liquid resuscitation. The correlation between the volume of liquid used in resuscitation and the level of blood chlorine was analyzed. RESULTS: The mean resuscitation duration was (15.0±2.4) hours, and the volume of liquid resuscitation was 3 4594 203 ml, with mean volume (3 910± 102) ml in 22 patients; blood sodium (mmol/L) and chlorine (mmol/L) levels were both significantly higher after resuscitation compared with those before resuscitation (Na(+): 145.83±1.85 vs. 139.67±2.25, Cl(-): 117.33±1.64 vs. 101.83±1.77, both P<0.05). Blood pH value, hematocrit (Hct), anion gap (AG, mmol/L), blood lactic acid (mmol/L) were slightly lowered after resuscitation (pH value: 7.39±0.02 vs. 7.42±0.02, Hct: 35.63±1.58 vs. 46.85±2.38, AG: 8.02±1.21 vs. 14.47±0.89, blood lactic acid: 1.10±0.18 vs. 1.97±0.15, P<0.05 or P <0.01). In addition, the level of blood chlorine was significantly correlated with the volume of liquid used in resuscitation (r=0.720 8,P<0.01). CONCLUSION: The target of liquid resuscitation in patients with SAP should be cautiously determined, including control of the volume of liquid for resuscitation, in order to avoid acid-base imbalance or hyperchloraemia. At the same time, the change in internal environment should be monitored.

[The clinical effectiveness of percutaneous drainage and laparotomy for patients with infective pancreatic necrosis].

OBJECTIVE: To compare the clinical effectiveness of percutaneous US- or CT-guided drainage and laparotomy for patients with infective pancreatic necrosis. METHODS: Data of 90 infective pancreatic necrosis patients admitted from January 2008 to December 2009 were included. They were divided into two groups by the different treatment choices. Twenty-seven patients in the percutaneous group received percutaneous US- or CT-guided drainage as first choice. After that a sump suction apparatus was applied for controlled drainage. If no improvement was achieved after 3 days, they would received operation soon. While patients in the laparotomy group received surgical drainage at the time when the diagnosis of infected pancreatic necrosis was confirmed. Continuous drainage was also applied for these ones. RESULTS: The percutaneous group had a significant low rate of reoperation (7.1% vs. 14.3%, P < 0.05) and postoperative residual abscesses (7.1% vs. 28.6%, P < 0.05). Furthermore, 48.1% of patients in percutaneous group successfully avoid laparotomy. In the regard of complications, the percutaneous group presented lower incidence of both single organ dysfunction (7.4% vs. 28.6%, P < 0.05), intestinal fistula (7.4% vs. 27.0%, P < 0.05) and long-term complications (3.7% vs. 22.2%, P < 0.05). In addition, the percutaneous group costed less medical resources as evidenced by shorter ICU duration (21.2 ± 9.7 vs. 28.7 ± 12.1, P < 0.01), shorter hospital duration (48.2 ± 12.5 vs. 59.6 ± 17.5, P < 0.05) and less expenditure (191 762 ± 5892 vs. 341 689 ± 10 854, P < 0.05). CONCLUSIONS: Percutaneous drainage can effectively lower the surgical rates and the rates of complications and reoperations in patients with infective pancreatic necrosis. Besides that, it could also reduce the cost of medical resources.

Machine Learning Models of Acute Kidney Injury Prediction in Acute Pancreatitis Patients.

Background. Acute kidney injury (AKI) has long been recognized as a common and important complication of acute pancreatitis (AP). In the study, machine learning (ML) techniques were used to establish predictive models for AKI in AP patients during hospitalization. This is a retrospective review of prospectively collected data of AP patients admitted within one week after the onset of abdominal pain to our department from January 2014 to January 2019. Eighty patients developed AKI after admission (AKI group) and 254 patients did not (non-AKI group) in the hospital. With the provision of additional information such as demographic characteristics or laboratory data, support vector machine (SVM), random forest (RF), classification and regression tree (CART), and extreme gradient boosting (XGBoost) were used to build models of AKI prediction and compared to the predictive performance of the classic model using logistic regression (LR). XGBoost performed best in predicting AKI with an AUC of 91.93% among the machine learning models. The AUC of logistic regression analysis was 87.28%. Present findings suggest that compared to the classical logistic regression model, machine learning models using features that can be easily obtained at admission had a better performance in predicting AKI in the AP patients.

Identification and functional characterization of a novel heterozygous missense variant in the LPL associated with recurrent hypertriglyceridemia-induced acute pancreatitis in pregnancy.

BACKGROUND: Acute pancreatitis in pregnancy (APIP) is a life-threatening disease for both mother and fetus. To date, only three patients with recurrent hypertriglyceridemia-induced APIP (HTG-APIP) have been reported to carry rare variants in the lipoprotein lipase (LPL) gene, which encodes the key enzyme responsible for triglyceride (TG) metabolism. Coincidently, all three patients harbored LPL variants on both alleles and presented with complete or severe LPL deficiency. METHODS: The entire coding regions and splice junctions of LPL and four other TG metabolism genes (APOC2, APOA5, GPIHBP1, and LMF1) were analyzed by Sanger sequencing in a Han Chinese patient who had experienced two episodes of HTG-APIP. The impact of a novel LPL missense variant on LPL protein expression and activity was analyzed by transient expression in HEK293T cells. RESULTS: A novel heterozygous LPL missense variant, p.His210Leu (c.629A > T), was identified in our patient. This variant did not affect protein synthesis but significantly impaired LPL secretion and completely abolished the enzymatic activity of the mutant protein. CONCLUSION: This report describes the first identification and functional characterization of a heterozygous variant in the LPL that predisposed to recurrent HTG-APIP. Our findings confirm a major genetic contribution to the etiology of individual predisposition to HTG-APIP.