Machine learning-based prediction model of acute kidney injury in patients with acute respiratory distress syndrome.

BACKGROUND: Acute kidney injury (AKI) can make cases of acute respiratory distress syndrome (ARDS) more complex, and the combination of the two can significantly worsen the prognosis. Our objective is to utilize machine learning (ML) techniques to construct models that can promptly identify the risk of AKI in ARDS patients. METHOD: We obtained data regarding ARDS patients from the Medical Information Mart for Intensive Care III (MIMIC-III) and MIMIC-IV databases. Within the MIMIC-III dataset, we developed 11 ML prediction models. By evaluating various metrics, we visualized the importance of its features using Shapley additive explanations (SHAP). We then created a more concise model using fewer variables, and optimized it using hyperparameter optimization (HPO). The model was validated using the MIMIC-IV dataset. RESULT: A total of 928 ARDS patients without AKI were included in the analysis from the MIMIC-III dataset, and among them, 179 (19.3%) developed AKI after admission to the intensive care unit (ICU). In the MIMIC-IV dataset, there were 653 ARDS patients included in the analysis, and among them, 237 (36.3%) developed AKI. A total of 43 features were used to build the model. Among all models, eXtreme gradient boosting (XGBoost) performed the best. We used the top 10 features to build a compact model with an area under the curve (AUC) of 0.850, which improved to an AUC of 0.865 after the HPO. In extra validation set, XGBoost_HPO achieved an AUC of 0.854. The accuracy, sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), and F1 score of the XGBoost_HPO model on the test set are 0.865, 0.813, 0.877, 0.578, 0.957 and 0.675, respectively. On extra validation set, they are 0.724, 0.789, 0.688, 0.590, 0.851, and 0.675, respectively. CONCLUSION: ML algorithms, especially XGBoost, are reliable for predicting AKI in ARDS patients. The compact model maintains excellent predictive ability, and the web-based calculator improves clinical convenience. This provides valuable guidance in identifying AKI in ARDS, leading to improved patient outcomes.

Biliary reconstruction with a pedicled gallbladder flap in patients during pancreaticoduodenectomy.

BACKGROUND: Stricture formation at the biliary-enteric anastomosis can cause serious complications after pancreaticoduodenectomy while the anastomotic size is reported to significantly affect stricture formation. In this study, we aimed to determine the effect of a pedicled gallbladder flap used as an alternative to biliary reconstruction during pancreaticoduodenectomy in patients with a nondilated extrahepatic bile duct. METHODS: Data of patients with a nondilated extrahepatic bile duct, who underwent pancreaticoduodenectomy between October 2012 and July 2015 at the Department of Hepatobiliary and Pancreaticosplenic Surgery at Beijing Chaoyang Hospital, were collected. A pedicled gallbladder flap for biliary reconstruction was consecutively performed in patients with morphologically normal gallbladder, whereas patients with abnormal gallbladder morphology accept conventional biliary reconstruction. RESULTS: A total of 29 patients were enrolled in this study with 17 patients using a pedicled gallbladder flap and 12 patients using the conventional technique. Patients of the two groups had similar preoperative and operative parameters as well as similar early complication rates. No patients in the former group experienced biliary stricture or transient episodes of cholangitis over the follow-up period. While in the latter group, one patient had biliary stricture in the 14th month which was cured by intervene treatment. Another two patients had intermittently mild-to-moderate elevations in liver enzymes level from the 11th month and the 18th month, respectively, and were treated with medication. CONCLUSIONS: Biliary reconstruction with a pedicled gallbladder graft can be used as an alternative in patients with a nondilated extrahepatic bile duct during pancreaticoduodenectomy.

Bilioenteric anastomotic stricture in patients with benign and malignant tumors: prevalence, risk factors and treatment.

BACKGROUND: Stricture formation at the bilioenteric anastomosis is a rare but important postoperative complication. However, information on this complication is lacking in the literature. In the present study, we aimed to assess its prevalence and predictive factors, and report our experience in managing bilioenteric anastomotic strictures over a ten-year period. METHODS: A total of 420 patients who had undergone bilioenteric anastomosis due to benign or malignant tumors between February 2001 and December 2011 were retrospectively reviewed. Univariate and multivariate modalities were used to identify predictive factors for anastomotic stricture occurrence. Furthermore, the treatment of anastomotic stricture was analyzed. RESULTS: Twenty-one patients (5.0%) were diagnosed with bilioenteric anastomotic stricture. There were 12 males and 9 females with a mean age of 61.6 years. The median time after operation to anastomotic stricture was 13.6 months (range, 1 month to 5 years). Multivariate analysis identified that surgeon volume (≤30 cases) (odds ratio: -1.860; P=0.044) was associated with the anastomotic stricture while bile duct size (>6 mm) (odds ratio: 2.871; P=0.0002) had a negative association. Balloon dilation was performed in 18 patients, biliary stenting in 6 patients, and reoperation in 4 patients. Five patients died of tumor recurrence, and one of heart disease. CONCLUSIONS: Bilioenteric anastomotic stricture is an uncommon complication that can be treated primarily by interventional procedures. Bilioenteric anastomosis may be performed by a surgeon in his earlier training period under the guidance of an experienced surgeon. Bile duct size >6 mm may play a protective role.

Characterization and evaluation of a new triosephosphate isomerase homologue from Haemaphysalis longicornis as a candidate vaccine against tick infection.

Haemaphysalis longicornis is an obligate hematophagous ectoparasite that transmits a variety of pathogens causing life­threatening diseases in humans and animals. Triosephosphate isomerase (TIM) is a key enzyme in glycometabolism, making in an interesting anti-tick vaccine candidate antigen. In this study, the open reading frame (ORF) of the TIM homologue from H. longicornis (HlTIM) was shown to consist of 747 bp encoding a protein of 248 amino acids. HlTIM gene expression was detected in all developmental stages and in all tissues of the unfed female tick by quantitative real-time PCR. The HlTIM gene was cloned and inserted into pET-32a (+) to obtain the recombinant HlTIM protein (rHlTIM) and its immunogenicity was confirmed by Western blot. ELISA results showed that rabbits immunized with rHlTIM produced a humoral immune response. A vaccine trial in rabbits against H. longicornis infestation demonstrated that the engorgement weight, oviposition and hatchability of ticks from the rH1TIM group was decreased by 8.6%, 35.4% and 17.3% respectively, compared to the histidine-tagged thioredoxin (Trx) control group. Considering the cumulative effect of vaccination on the evaluated parameters, results showed 50.9% efficacy in the rHlTIM group. The data reported here demonstrate that rHlTIM has potential for further development of a new candidate vaccine for tick control.

Gene cloning, analysis and effect of a new lipocalin homologue from Haemaphysalis longicornis as a protective antigen for an anti-tick vaccine.

Haemaphysalis longicornis is distributed worldwide and transmits a variety of pathogens, causing human and animal disease. Use of chemical acaricides, as a primary tick control method, has several disadvantages, including acaricide resistance, environmental damage and residue accumulation in livestock. Development of a livestock vaccination aimed at a tick protective antigen could be an effective, labor-saving and environmentally-friendly method of reducing tick infestation and transmission of tick-borne pathogens. Lipocalins are low molecular weight proteins that play important roles in blood feeding, immune response and reproduction in ticks. In our study, the open reading frame (ORF) of a lipocalin homologue from H. longicornis (HlLIP) was successfully cloned, which consisted of 387 bp encoding a protein of 128 amino acids. The HlLIP protein sequence showed a close sequence homology with Ixodes persulcatus lipocalin. The HlLIP gene was constitutively detected in all developmental stages and in all tissues of the unfed female tick. The ORF of the HlLIP gene was sub-cloned into pET-32a (+) to obtain the recombinant protein (rHlLIP) and its immunogenicity was comfirmed by western blot. A vaccination trial on rabbits against H. longicornis infestation demonstrated that the rHlLIP protein could significantly prolong the period of tick blood feeding, and reduce tick engorged weight, oviposition and egg hatching rate. The vaccination efficacy of the rHlLIP protein was 60.17 % based on engorged weight, oviposition and egg hatching rate of ticks. The results obtained in this study demonstrate that rHlLIP protein is a promising antigen that could potentially be developed as a vaccine against H. longicornis infestation.

Evaluation on two types of paramyosin vaccines for the control of Haemaphysalis longicornis infestations in rabbits.

BACKGROUND: Haemaphysalis longicornis is an obligate hematophagous ectoparasite that transmits a variety of pathogens causing life-threatening diseases in humans and animals. Paramyosin (Pmy) is not only an invertebrate-specific myofibrillar protein but also an important immunomodulatory protein. Therefore, it is one of the ideal candidate antigens for vaccines. METHODS: We conducted two vaccine trials to evaluate the protective efficacy of Pmy recombinant protein (rPmy) and peptide vaccine (KLH-LEE). Each rabbit was immunized with three doses of rPmy or KLH-LEE adjuvanted with Freund's complete/incomplete at 500 µg/dose at 2-week intervals before challenge with 40 female H. longicornis/rabbit. PBS plus adjuvant, Trx or KLH was used as control group. The antibodies of rabbits were detected by ELISA. Then, female ticks were fed on the rabbits until detachment. RESULTS: ELISA results showed that both vaccines induced rabbits to produce antibodies. Compared with the Trx group, the engorgement weight, oviposition and hatchability of the rPmy group decreased by 8.87%, 26.83% and 38.86%, respectively. On the other hand, engorgement weight, oviposition and hatchability of female ticks in the KLH-LEE group correspondingly resulted in 27.03%, 53.15% and 38.40% reduction compared with that of the KLH group. Considering the cumulative effect of vaccination on the evaluated parameters, results showed 60.37% efficacy of the rPmy vaccine formulation and 70.86% efficacy in the KLH-LEE group. CONCLUSIONS: Pmy and particularly epitope LEE have potential for further development of an effective candidate vaccine to protect the host against tick infection. GRAPHIC ABSTARCT.

Fyn knockdown inhibits migration and invasion in cholangiocarcinoma through the activated AMPK/mTOR signaling pathway.

Cholangiocarcinoma (CCA) is a rare and fatal tumor. In previous decades, there has been a steady increase in the incidence and mortality rates of this tumor worldwide. Metastasis is regarded as the major factor that contributes to poor prognosis in CCA patients. Studies therefore aim to develop novel therapeutic targets to control CCA metastasis. Fyn is known to enhance expression and promote metastasis in various cancers, including pancreatic cancer, prostate cancer and colorectal cancer. However, the exact function and mechanism of Fyn in CCA metastasis remains unclear. In the present study, mRNA and protein expression levels of Fyn, AMP-activated protein kinase (AMPK), phosphorylated (p-)AMPK, mammalian target of rapamycin (mTOR) and p-mTOR were measured, using the reverse transcription-quantitative polymerase chain reaction and western blot analysis, in CCA tissues and cell lines. In addition, Transwell assays were used to determine the migratory and invasive abilities of human CCA QBC939, following transfection. In the present study, it was found that Fyn was overexpressed in CCA cell lines. Fyn knockdown inhibited CCA cell migration and invasion. Furthermore, it was demonstrated that Fyn knockdown induces phosphorylation of AMPK, inhibits downstream phosphorylation of mTOR, and activate the AMPK/mTOR signaling pathway. Compound C, an AMPK inhibitor, inhibited the AMPK/mTOR signaling pathway, and reversed the effect of Fyn knockdown on migration and invasion of CCA cells. In conclusion, the present study suggests that Fyn knockdown inhibits cell migration and invasion by regulating the AMPK/mTOR signaling pathway in CCA cell lines and that Fyn knockdown is a potential target for anti-CCA therapy.

Isolated hepatic tuberculosis in the caudate lobe mimicking intrahepatic carcinoma.

Although tuberculosis (TB) remains a worldwide epidemic, isolated hepatic TB is an extremely rare entity and poorly described in the literature. Isolated hepatic TB may pose a diagnostic dilemma due to the non-specific clinical symptoms and imaging features. We present a case of a 54-year-old female with an isolated caseating granulomatous lesion at the caudate lobe of liver involving the pancreatic head.