Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients: A retrospective cohort study.

BACKGROUND: Early systemic anticoagulation (SAC) is a common practice in acute necrotizing pancreatitis (ANP), and its impact on in-hospital clinical outcomes had been assessed. However, whether it affects long-term outcomes is unknown. This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients. METHODS: During January 2013 and December 2018, ANP patients admitted within 7 days from the onset of abdominal pain were screened. The primary outcome was 90-day readmission after discharge. Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission. RESULTS: A total of 241 ANP patients were enrolled, of whom 143 received early SAC during their hospitalization and 98 did not. Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis (SVT) [risk ratio (RR) = 0.40, 95% CI: 0.26-0.60, P < 0.01] and lower 90-day readmission with an RR of 0.61 (95% CI: 0.41-0.91, P = 0.02) than those who did not. For the quality of life, patients who received early SAC had a significantly higher score in the subscale of vitality (P = 0.03) while the other subscales were all comparable between the two groups. Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57 (95% CI: 0.34-0.96, P = 0.04). Mediation analysis showed that SVT mediated 37.0% of the early SAC-90-day readmission causality. CONCLUSIONS: The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients, and reduced SVT incidence might be the primary contributor.

A hybrid model of modal decomposition and gated recurrent units for short-term load forecasting.

Electrical load forecasting is important to ensuring power systems are operated both economically and safely. However, accurately forecasting load is difficult because of variability and frequency aliasing. To eliminate frequency aliasing, some methods set parameters that depend on experiences. The present study proposes an adaptive hybrid model of modal decomposition and gated recurrent units (GRU) to reduce frequency aliasing and series randomness. This model uses average sample entropy and mutual correlation to jointly determine the modal number in the decomposition. Random adjustment parameters were introduced to the Adam algorithm to improve training speed. To assess the applicability and accuracy of the proposed hybrid model, it was compared with some state of the art forecasting methods. The results, which were validated by actual data sets from Shaanxi province, China, show that the proposed model had a higher accuracy and better reliability compared to the other forecasting methods.

Initial suction drainage decreases severe postoperative complications after pancreatic trauma: A cohort study.

BACKGROUND: Few studies have addressed the question of which drain types are more beneficial for patients with pancreatic trauma (PT). AIM: To investigate whether sustained low negative pressure irrigation (NPI) suction drainage is superior to closed passive gravity (PG) drainage in PT patients. METHODS: PT patients who underwent pancreatic surgery were enrolled consecutively at a referral trauma center from January 2009 to October 2021. The primary outcome was defined as the occurrence of severe complications (Clavien-Dindo grade ≥ Ⅲb). Multivariable logistic regression was used to model the primary outcome, and propensity score matching (PSM) was included in the regression-based sensitivity analysis. RESULTS: In this study, 146 patients underwent initial PG drainage, and 50 underwent initial NPI suction drainage. In the entire cohort, a multivariable logistic regression model showed that the adjusted risk for severe complications was decreased with NPI suction drainage [14/50 (28.0%) vs 66/146 (45.2%); odds ratio (OR), 0.437; 95% confidence interval (CI): 0.203-0.940]. After 1:1 PSM, 44 matched pairs were identified. The proportion of each operative procedure performed for pancreatic injury-related and other intra-abdominal organ injury-related cases was comparable in the matched cohort. NPI suction drainage still showed a lower risk for severe complications [11/44 (25.0%) vs 21/44 (47.7%); OR, 0.365; 95%CI: 0.148-0.901]. A forest plot revealed that NPI suction drainage was associated with a lower risk of Clavien-Dindo severity in most subgroups. CONCLUSION: This study, based on one of the largest PT populations in a single high-volume center, revealed that initial NPI suction drainage could be recommended as a safe and effective alternative for managing complex PT patients.

Maternal weight and its association with risk of overweight in offspring: a trajectory analysis from a birth cohort in China.

BACKGROUND: Most studies on the association of maternal pregnancy weight with offspring weight trajectory have a short follow-up time. This study aimed to explore the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) with childhood weight trajectories in a 7-year birth cohort. METHODS: A total of 946 mother-child pairs (467 boys and 479 girls) from a longitudinal birth cohort in Tianjin City, China, were included in this study, ranging from pregnancy to offspring at 7 years. The outcome variable was defined as overweight or not overweight in offspring at the last round. A group-based trajectory model was applied to identify childhood BMI trajectory groups. RESULTS: Five discrete BMI trajectory groups were identified and characterized as constant underweight (25.2%), constant normal weight (42.8%), and high or increasing trajectory [at risk of overweight (16.9%), progressive overweight (11.0%) and progressive obesity (4.1%)]. Maternal prepregnancy overweight was associated with 1.72 (95% CI 1.14-2.60, P = 0.01) to 4.02 (95% CI 1.94-8.36, P < 0.001) times the risk of all high or increasing trajectory groups, and excessive GWG was related to groups at risk of overweight [relative risk ratio (RRR) 2.09, 95% CI 1.27-3.46, P = 0.004] and progressive obesity (RRR 3.33, 95% CI 1.13-9.79, P = 0.029). Children in all high or increasing trajectory groups were associated with greater overweight risk at the last round [risk ratios (RRs) ranged from 3.54 (95% CI 2.53-4.95, P < 0.001) to 6.18 (95% CI 4.05-9.42, P < 0.001)]. CONCLUSION: Maternal prepregnancy overweight and excessive gestational weight gain were associated with increasing or high-level childhood body mass index trajectories as well as a greater risk of overweight at 7 years.

A robust maximum correntropy forecasting model for time series with outliers.

It is of great significance to develop a robust forecasting method for time series. The reliability and accuracy of the traditional model are reduced because the series is polluted by outliers. The present study proposes a robust maximum correntropy autoregressive (MCAR) forecasting model by examining the case of actual power series of Hanzhong City, Shaanxi province, China. In order to reduce the interference of the outlier, the local similarity between data is measured by the Gaussian kernel width of correlation entropy, and the semi-definite relaxation method is used to solve the parameters in MCAR model. The results show that the MCAR model in comparison with deep learning methods, in terms of the average value of the mean absolute percentage error (MAPE), performed better by 1.63%. It was found that maximum correntropy is helpful for reducing the interference of outliers.

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.

Elevated serum HbA1c level, rather than previous history of diabetes, predicts the disease severity and clinical outcomes of acute pancreatitis.

INTRODUCTION: The aim of our study is to explore the value of serum glycosylated hemoglobin A1c (HbA1c) in disease severity and clinical outcomes of acute pancreatitis (AP). RESEARCH DESIGN AND METHODS: Patients with AP were included from January 2013 to December 2020, retrospectively, dividing into normal serum HbA1c level (N-HbA1c) group and high serum HbA1c level (H-HbA1c) group according to the criteria HbA1c <6.5%. We compared patient characteristics, biochemical parameters, disease severity, and clinical outcomes of patients with AP in two groups. Besides, we evaluated the efficacy of serum HbA1c to predict organ failure (OF) in AP patients by receiver operating curve (ROC). RESULTS: We included 441 patients with AP, including 247 patients in N-HbA1c group and 194 patients in H-HbA1c group. Serum HbA1c level was positively correlated with Atlanta classification, systemic inflammatory response syndrome, local complication, and OF (all p<0.05). Ranson, BISAP (bedside index of severity in acute pancreatitis), and CT severity index scores in patients with H-HbA1c were markedly higher than those in patients with N-HbA1c (all p<0.01). ROC showed that the best critical point for predicting the development of OF in AP with serum HbA1c is 7.05% (area under the ROC curve=0.79). Logistic regression analysis showed H-HbA1c was the independent risk factor for the development of OF in AP. Interestingly, in patients with presence history of diabetes and HbA1c <6.5%, the severity of AP was significantly lower than that in H-HbA1c group. Besides, there was no significant difference between with and without history of diabetes in N-HbA1c group. CONCLUSIONS: Generally known, diabetes is closely related to the development of AP, and strict control of blood glucose can improve the related complications. Thus, the level of glycemic control before the onset of AP (HbA1c as an indicator) is the key to poor prognosis of AP, rather than basic history of diabetes. Elevated serum HbA1c level can become the potential indicator for predicting the disease severity of AP.

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.

Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression.

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

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.

Predicting the mortality risk of acute respiratory distress syndrome: radial basis function artificial neural network model versus logistic regression model.

To predict the mortality of acute respiratory distress syndrome (ARDS) by using a radial basis function (RBF) artificial neural network (ANN) model. This study included 217 patients who were admitted between June 2013 and November 2019. The RBF ANN model and logistic regression (LR) model were based on twelve factors related to ARDS. Statistical indexes were used to determine the value of the prediction in the two models. The sensitivity, specificity and accuracy of the RBF ANN model to predict mortality were 83.6%, 88.5% and 82.5%, respectively. Significant differences were found between the RBF ANN and LR models (P < 0.05). When the RBF ANN model was used to identify ARDS, the area under the ROC curve was 0.854 ± 0.029. LDH, organ failure, SP-D and PaO2/FiO2 were the most important independent variables. The RBF ANN model was more likely to predict the mortality of ARDS than the LR model. In addition, it can extract informative risk factors for ARDS.

Resilience, coping style, and COVID-19 stress: effects on the quality of life in frontline health care workers.

The aims of the study were to assess the contribution of resilience, coping style, and COVID-19 stress on the quality of life (QOL) in frontline health care workers (HCWs). The study was a cross-sectional surveyperformed among 309 HCWs in a tertiaryhospital during the outbreak of COVID-19 in China. Data were collected through an anonymous, self-rated questionnaire, including demographic data, a 10-item COVID-19 stress questionnaire, Generic QOL Inventory-74, Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire. Hierarchical regression was used to analyse the relationship between the study variables and the QOL. Among the 309 participants, resilience and active coping were positively correlated with the QOL (P<0.001), whereas, working in confirmed case wards, COVID-19 stress, and passive coping were negatively correlated with the QOL (P<0.001). Resilience and the active coping were negatively correlated with COVID-19 stress (P<0.001). Resilience, coping style,and COVID-19 stressaccounted for 32%, 13%, and 8% of the variance in predicting the Global QOL, respectively. In conclusion, working in confirmed COVID-19 case wards and COVID-19 stress impaired the QOL in HCWs. Psychological intervention to improve the resilience and coping style, and reduce COVID-19 stress are important in improving the QOL and mental health of HCWs.

Analysis of efficacy and safety of patients after LASIK surgery in 20 years / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate long-term efficacy and safety of patients after excimer laser in situ keratomileusis(LASIK)surgery in 20a.METHODS: A retrospective study.Patients who underwent LASIK in our hospital from January 1998 to December 2001 were recruited. The patients were notified by telephone to the outpatient for follow-up. The collected data included demographic characteristics(gender and age), preoperative uncorrected distance visual acuity(UCVA)and best corrected visual acuity(BCVA), preoperative diopter, intraoperative corneal flap thickness and corneal stromal residual thickness(RST). The main indicators were long-term efficacy index, safety index, UCVA, BCVA, corneal thickness and axial length. The slit lamp, fundus and optical coherence tomography(OCT)examination were performed at the same time.RESULTS: A total of 95 patients(190 eyes)were recruited. At the final postoperative visit, there were 71 patients(142 eyes, 74.7%)had UCVA≥1.0, and 82 patients(164 eyes, 86.3%)had BCVA≥1.0. There were 2 eyes among them had bad BCVA(≤0.6)due to macular retinoschisis and glaucoma, respectively, while other patients' BCVA was 0.8. There was no significant correlation between the UCVA and BCVA of patients after surgery in 20a and the factors such as age at surgery, preoperative diopter and corneal thickness(P&#x003E;0.05), but there was a negative correlation with the increase of axis length(rs=-0.32, -0.31, all P&#x003C;0.05). UCVA and BCVA were positively correlated with corneal stromal residual thickness at the last postoperative follow-up(P&#x003C;0.05). The safety and efficacy indexes of LASIK after surgery in 20a were 1.00±0.10 and 0.83±0.27, respectively. During the follow-up, no patients were found to have corneal ectasia and complications related to corneal flap, and no patients underwent secondary surgery. No patients with corneal dryness were found after silt lamp examination.CONCLUSION: LASIK after surgery in 20a shows good safety and efficacy.

Observation and study on uncorrected distance visual acuity and ocular adjustment function before and after excimer laser photorefractive keratectomy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the changes of uncorrected distance visual acuity(UCDVA)and ocular accommodation before and after excimer laser photorefractive keratectomy(PRK).METHODS: A retrospective study. There were 120 patients(240 eyes)who underwent PRK surgery in our center from December 2017 to December 2019 divided into two groups according to the diopter of spherical equivalent(SE): 70 cases with SE≤-6.00D in the mild to moderate myopia group and 50 cases with -6.00D&#x003C;SE≤-9.00D in the high myopia group which were observed and analyzed. The UCDVA(LogMAR), monocular accommodative amplitude(AMP), negative relative accommodation(NRA), positive relative accommodation(PRA)and monocular accommodative flipper(AF)were measured before and after operation at 1wk, 1 and 3mo. RESULTS: In the group of low-moderate myopia and high-myopia group, the UCDVA at 1wk, 1 and 3 mo after operation was significantly increased compared with those before operation(all P&#x003C;0.01). The increase of UCDVA of low to moderate myopia group was better than that in the high myopia group at 3mo after operation(P&#x003C;0.05). Monocular AMP in the both groups firstly decreased and increased afterwards, and there was a significant decrease than that before operation at 1wk and 1mo after operation(P&#x003C;0.01). AMP reached and was better than that before operation at 3mo after operation(P&#x003C;0.01). The increase of low to moderate myopia group was both higher and faster than that of high myopia group. Compared with PRA before operation, the patients of low to moderate myopia group decreased at 1wk after operation(P&#x003C;0.01), postoperative levels at 1mo recovered to preoperative level(P&#x003E;0.05)and postoperative at 3mo was superior to preoperative operation(P&#x003C;0.05); High myopia group did not change significantly at 1wk and 1mo after operation compared with preoperative operation(P&#x003E;0.05), and increased at 3mo after operation compared with preoperative level(P&#x003C;0.01). For low to moderate myopia group, there was no significant difference in preoperative and postoperative NRA, and at 1wk after operation, NRA of high myopia group temporarily increased compared with preoperative operation(P&#x003C;0.01). At 1mo after operation, it returned to the preoperative level(P&#x003E;0.05), and significantly increased at 3mo after operation compared with preoperative operation(P&#x003C;0.01). Monocular AF for both groups significantly decreased at 1wk after operation compared with preoperative operation, recovered at 1mo after operation and was significantly better at 3mo after operation(all P&#x003C;0.01); The low-to-moderate group increased more than the high-myopia group.CONCLUSION: PRK has a good correction effect for myopia below -9.00D, and people in low to moderate myopia have a better postoperative UCDVA correction effect than those in high myopia. The eye accommodation will be abnormal in a short period after operation. The recovery and improvement time of accommodative function in low-moderate myopia group are shorter than that in high myopia group, but both groups can recover and improve at 3mo after operation compared with the preoperative levels.

Bioelectrical impedance analysis-guided fluid management promotes primary fascial closure after open abdomen: a randomized controlled trial.

BACKGROUND: Fluid overload (FO) after resuscitation is frequent and contributes to adverse outcomes among postinjury open abdomen (OA) patients. Bioelectrical impedance analysis (BIA) is a promising tool for monitoring fluid status and FO. Therefore, we sought to investigate the efficacy of BIA-directed fluid resuscitation among OA patients. METHODS: A pragmatic, prospective, randomized, observer-blind, single-center trial was performed for all trauma patients requiring OA between January 2013 and December 2017 to a national referral center. A total of 140 postinjury OA patients were randomly assigned in a 1:1 ratio to receive either a BIA-directed fluid resuscitation (BIA) protocol that included fluid administration with monitoring of hemodynamic parameters and different degrees of interventions to achieve a negative fluid balance targeting the hydration level (HL) measured by BIA or a traditional fluid resuscitation (TRD) in which clinicians determined the fluid resuscitation regimen according to traditional parameters during 30 days of ICU management. The primary outcome was the 30-day primary fascial closure (PFC) rate. The secondary outcomes included the time to PFC, postoperative 7-day cumulative fluid balance (CFB) and adverse events within 30 days after OA. The Kaplan-Meier method and the log-rank test were utilized for PFC after OA. A generalized linear regression model for the time to PFC and CFB was built. RESULTS: A total of 134 patients completed the trial (BIA, n = 66; TRD, n = 68). The BIA patients were significantly more likely to achieve PFC than the TRD patients (83.33% vs. 55.88%, P < 0.001). In the BIA group, the time to PFC occurred earlier than that of the TRD group by an average of 3.66 days (P < 0.001). Additionally, the BIA group showed a lower postoperative 7-day CFB by an average of 6632.80 ml (P < 0.001) and fewer complications. CONCLUSION: Among postinjury OA patients in the ICU, the use of BIA-guided fluid resuscitation resulted in a higher PFC rate and fewer severe complications than the traditional fluid resuscitation strategy.

A cohort autopsy study defines COVID-19 systemic pathogenesis.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

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.

Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy.

Trauma-induced coagulopathy (TIC) is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage. Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC, while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2-85.1% of trauma patients, in whom it can increase the risk of thrombotic events and mortality by 2- to 4-fold. Therefore, the Chinese People's Liberation Army Professional Committee of Critical Care Medicine and the Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association jointly formulated this Chinese Expert Consensus comprising 15 recommendations for the definition, pathophysiological mechanism, assessment, prevention, and treatment of trauma-induced hypercoagulopathy.