Association of blood cadmium concentration with chronic obstructive pulmonary disease progression: a prospective cohort study.

BACKGROUND: Prior studies in patients with chronic obstructive pulmonary disease (COPD) had indicated a potential correlation between cadmium (Cd) exposure and reduction in lung function. Nevertheless, the influence of Cd exposure on the progression of COPD remained unknown. Exploring the relationship between Cd exposure and the progression of COPD was the aim of this investigation. METHODS: Stable COPD patients were enrolled. Blood samples were collected and lung function was evaluated. Regular professional follow-ups were conducted through telephone communications, outpatient services, and patients' hospitalization records. RESULTS: Each additional unit of blood Cd was associated with upward trend in acute exacerbation, hospitalization, longer hospital stay, and death within 2 years. Even after adjusting for potential confounding factors, each 1 unit rise in blood Cd still correlated with a rise in the frequencies of acute exacerbation, longer hospital stay, and death. Moreover, COPD patients with less smoking amount, lower lung function and without comorbidities were more vulnerable to Cd-induced disease deterioration. CONCLUSION: Patients with COPD who have higher blood Cd concentration are susceptible to worse disease progression.

Enhancing Multi-species Liver Microsomal Stability Prediction through Artificial Intelligence.

Liver microsomal stability, a crucial aspect of metabolic stability, significantly impacts practical drug discovery. However, current models for predicting liver microsomal stability are based on limited molecular information from a single species. To address this limitation, we constructed the largest public database of compounds from three common species: human, rat, and mouse. Subsequently, we developed a series of classification models using both traditional descriptor-based and classic graph-based machine learning (ML) algorithms. Remarkably, the best-performing models for the three species achieved Matthews correlation coefficients (MCCs) of 0.616, 0.603, and 0.574, respectively, on the test set. Furthermore, through the construction of consensus models based on these individual models, we have demonstrated their superior predictive performance in comparison with the existing models of the same type. To explore the similarities and differences in the properties of liver microsomal stability among multispecies molecules, we conducted preliminary interpretative explorations using the Shapley additive explanations (SHAP) and atom heatmap approaches for the models and misclassified molecules. Additionally, we further investigated representative structural modifications and substructures that decrease the liver microsomal stability in different species using the matched molecule pair analysis (MMPA) method and substructure extraction techniques. The established prediction models, along with insightful interpretation information regarding liver microsomal stability, will significantly contribute to enhancing the efficiency of exploring practical drugs for development.

Radiofrequency radiation reshapes tumor immune microenvironment into antitumor phenotype in pulmonary metastatic melanoma by inducing active transformation of tumor-infiltrating CD8+ T and NK cells.

Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM). Mouse model of PMM was established by tail vein injection of B16F10 cells. From day 3 after injection, the mice were exposed to RFR at an average specific absorption rate of 9.7 W/kg for 1 h per day for 14 days. After RFR exposure, lung tissues were harvested and RNAs were extracted for transcriptome sequencing; PMM-infiltrating immune cells were isolated for single-cell RNA-seq analysis. We showed that RFR exposure significantly impeded PMM progression accompanied by remodeled TIME of PMM via altering the proportion and transcription profile of tumor-infiltrating immune cells. RFR exposure increased the activation and cytotoxicity signatures of tumor-infiltrating CD8+ T cells, particularly in the early activation subset with upregulated genes associated with T cell cytotoxicity. The PD-1 checkpoint pathway was upregulated by RFR exposure in CD8+ T cells. RFR exposure also augmented NK cell subsets with increased cytotoxic characteristics in PMM. RFR exposure enhanced the effector function of tumor-infiltrating CD8+ T cells and NK cells, evidenced by increased expression of cytotoxic molecules. RFR-induced inhibition of PMM growth was mediated by RFR-activated CD8+ T cells and NK cells. We conclude that noninvasive RFR exposure induces antitumor remodeling of the TIME, leading to inhibition of tumor progression, which provides a promising novel strategy for TIME priming and potential combination with cancer immunotherapy.

Impacts of cardiometabolic risk factors and alcohol consumption on all-cause mortality among MASLD and its subgroups.

BACKGROUND AND AIMS: Recently, metabolic dysfunction-associated steatotic liver disease (MASLD) has been introduced. However, research on this new nomenclature and definition remains limited. This study aims to assess the impact of cardiometabolic risk factors and alcohol consumption on all-cause mortality in MASLD and its subgroups. METHODS AND RESULTS: We included 2408 participants with MASLD in NHANES III and their linked mortality through 2019. MASLD patients were divided into two groups based on alcohol consumption: Pure MASLD and MetALD. The Cox proportional hazard model was used to assess the association between factors and all-cause mortality. During the median 26.0-year follow-up, there were 1040 deaths. The multivariable Cox regression analysis revealed a significant increase of over two-fold in the all-cause mortality rate among patients with four or more cardiometabolic risk factors compared to those with only one. When focusing on each component of cardiometabolic risk factors individually, only diabetes and hypertension were significantly associated with all-cause mortality (p < 0.05). In a subgroup analysis, each additional cardiometabolic factor was linked to an increase in all-cause mortality in both pure MASLD (hazard ratio 1.16; 95% CI 1.06-1.28; p = 0.002) and MetALD (HR 1.77; 95% CI 1.26-2.49; p = 0.001). Notably, an elevation in alcohol consumption was significantly associated with an increase in all-cause mortality rate only in the MetALD (p < 0.001). CONCLUSIONS: This study found that the presence of diabetes or hypertension was significantly associated with all-cause mortality. We also explored the different impacts of these factors and alcohol consumption within MASLD subgroups.

Clinical characteristics analysis of pediatric spinal cord injury without radiological abnormality in China: a retrospective study.

PURPOSE: This study aims to analyze the clinical characteristics of Chinese children with spinal cord injury (SCI) without radiographic abnormality (SCIWORA) and explore their contributing factors and mechanisms of occurrence. METHODS: A retrospective analysis was conducted on the clinical data of pediatric patients diagnosed with SCIWORA from January 2005 to May 2020. Epidemiological, etiological, mechanistic, therapeutic, and outcome aspects were analyzed. RESULTS: A total of 47 patients with SCIWORA were included in this study, comprising 16 males and 31 females. The age range was 4 to 12 years, with an average age of 7.49 ± 2.04 years, and 70% of the patients were below eight. Sports-related injuries constituted 66%, with 70% attributed to dance backbend practice. Thoracic segment injuries accounted for 77%. In the American Spinal Injury Association (ASIA) classification, the combined proportion of A and B grades accounted for 88%. Conservative treatment was chosen by 98% of the patients, with muscle atrophy, spinal scoliosis, hip joint abnormalities, and urinary system infections being the most common complications. CONCLUSION: SCIWORA in Chinese children is more prevalent in those under eight years old, with a higher incidence in females than males. Thoracic spinal cord injuries are predominant, dance backbend as a primary contributing factor, and the social environment of "neijuan" is a critical potential inducing factor. Furthermore, the initial severity of the injury plays a decisive role in determining the prognosis of SCIWORA.

Incremental prognostic utility of left ventricular and left atrial strains in coronary artery disease patients with reduced systolic function.

OBJECTIVE: This study aimed to investigate the predictive value of left ventricular global longitudinal strain (GLS) and left atrial reservoir strain (LARS) on adverse events in chronic coronary artery disease (CAD) patients with reduced systolic function. METHODS: A total of 192 consecutive patients clinically diagnosed with chronic CAD and left ventricular ejection fraction (LVEF) ≤ 50% were finally included. Multiple strain parameters were analyzed with speckle tracking echocardiography. The composite endpoint included all-cause mortality, rehospitalization due to heart failure, myocardial infarction, and stroke. RESULTS: Patients experiencing the endpoint showed lower LVEF, lower absolute GLS and LARS than those without events. Both GLS (AUC = 0.82 [GLS] vs. 0.58 [LVEF], p < 0.001) and LARS (AUC = 0.71 [LARS] vs. 0.58 [LVEF], p = 0.033) were superior to LVEF in predicting adverse events. Multivariate cox regression analysis showed that both GLS (hazard ratio, 0.71; 95% CI, 0.63-0.79; p < 0.001) and LARS (hazard ratio, 0.96; 95% CI, 0.93-0.98; p < 0.001) were independent predictors for the endpoint. The addition of LARS (global chi-squared, 35.7 vs. 17.4; p < 0.05), GLS (global chi-squared, 58.6 vs. 17.4; p < 0.05) or both LARS and GLS (global chi-squared, 79.6 vs. 17.4; p < 0.05) to LVEF in the prediction model significantly improved its performance. The same significant improvement was also shown in the subgroups of mild (30% < LVEF ≤ 50%) and severe (LVEF ≤ 30%) reduced systolic function. CONCLUSIONS: Regarding CAD patients with reduced LVEF, both GLS and LARS are superior to LVEF in predicting adverse events, providing significant incremental value to LVEF.

Ultrasound evaluation of the cardiovascular system in offspring conceived through assisted reproductive technology.

With the widespread application of assisted reproductive technology, the health issues of offspring conceived through assisted reproductive technology have also received increasing attention. Animal experiments and clinical studies have found subclinical adverse changes in the cardiovascular system of assisted reproductive offspring. Assisted reproductive technology itself may be just one of the many factors contributing to this phenomenon, with epigenetics playing an important role. Ultrasound technology can be used to assess the morphological structure and function of the cardiovascular system in assisted reproductive offspring from the fetal stage, providing the possibility to study the potential cardiovascular damage in this large population. This review aims to explore the effects and mechanisms of assisted reproductive technology on the cardiovascular system of offspring and provide a review of the research progress in ultrasound technology in this area.

Accumulating awareness on the clinical significance and relevance of frailty in cirrhosis: Time to dig deeper into mechanistic basis!

Frailty corresponds to an emerging construct in the hepatology which is originally introduced as a validated geriatric syndrome regarding increased vulnerability to pathophysiological stressors. As for patients with cirrhosis, the presence of frailty is indicative of debilitating conditions that subjects are prone to deleterious acute insults and have difficulties to restore even if the underlying liver function partially returned to normal levels. Since this conceptual development, a variety of tools assessing frailty have been proposed and evaluated in the context of cirrhosis. A recent performance-based metric for frailty, designated as Liver Frailty Index, has broadly been applied in patients with cirrhosis and exhibited acceptable predictive ability in relation to disease progression, mortality and hospitalization. However, those functional tests measuring frailty may be impossible to perform in circumstance that patients are critically ill or undergoing detrimental events. An interesting modality indicates the use of alternative tests to evaluate frailty, which may be more adaptable and of choice for specific subgroups. The interrelation between frailty and various cirrhosis-associated pathological entities is of clinical importance and implication. Noticeably, it is imperative to clarify these complex linkages to highlight novel therapeutic targets or interventional endpoints. The efficient and effective management of frailty is still challenging, but many attempts have been made to overcome barriers of affordability and availability. Some clinical trials on small scale revealed that home-based exercise and individualized nutrition therapy show benefits in patients with cirrhosis, and high adherence to the treatment regimen may direct better efficacy and performance.

Low 15d-PGJ2 status is associated with oxidative stress in chronic obstructive pulmonary disease patients.

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent nuclear receptor and highly expressed in human and rodent lungs. 15-Deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), known for cyclopentenone prostaglandin, is the endogenous ligand of PPARγ. However, the associations among PPARγ, 15d-PGJ2 and chronic obstructive pulmonary disease (COPD) were unclear. METHODS: All 130 fasting blood samples and 40 lung specimens were obtained from COPD patients and control subjects. Serum 15d-PGJ2 was detected by ELISA. The expressions of oxidative stress indicators were measured using western blotting and PPARγ nuclei were evaluated with immunohistochemistry in lungs. The associations among serum 15d-PGJ2, pulmonary PPARγ and oxidative stress indicators, and COPD were estimated. RESULTS: Serum 15d-PGJ2 was reduced in COPD patients compared with healthy volunteers. Linear and logistic regression analysis indicated that serum 15d-PGJ2 was positively associated with pulmonary function in COPD patients. In addition, PPARγ-positive nuclei were reduced and oxidative stress indicators, included HO-1 and NOX-4, were increased in lungs of COPD patients. Further correlative analysis suggested that pulmonary function parameters was positively correlated with serum 15d-PGJ2 and pulmonary PPARγ-positive nuclei, inversely related to oxidative stress indicators in lungs of COPD patients. Pretreatment with 15d-PGJ2 obviously attenuated TNFα-induced oxidative stress in BEAS-2B cells. CONCLUSIONS: Serum 15d-PGJ2 and pulmonary PPARγ are reduced, and oxidative stress is elevated in COPD patients. Serum 15d-PGJ2 is inversely associated with oxidative stress in COPD patients.

The Use of Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide for Preventing Vertical Transmission of Hepatitis B.

BACKGROUND: Mother-to-child transmission (MTCT) of hepatitis B virus may occur in highly viremic mothers despite the infants receiving appropriate immunoprophylaxis. We aimed to review tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) data for preventing MTCT. METHODS AND DATA SELECTION: We performed a systematic review between January 1, 2015 and December 31, 2021 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases. Data was extracted from randomized controlled trials or cohort studies in English or Chinese. The outcomes of interest included the efficacy and safety of TDF versus TAF or TDF/TAF versus placebo for preventing MTCT (PROSPERO registration: CRD42021256656). RESULTS: Data from forty-three studies (13 randomized controlled trials, 30 nonrandomized studies) were included in the review. All infants in the studies received appropriate immunoprophylaxis. Among 3656 highly viremic mothers treated with TDF, hepatitis B virus DNA suppression to the levels <200,000 IU/mL at delivery was achieved in 34% to 100% of mothers. MTCT rates were 0 to 5% and 2 to 83% in mothers treated with TDF and in those who received no treatment, respectively. Congenital malformation rates were 0 to 2.1% in the TDF groups, which did not differ from the nontreated groups. Similar findings were reported in 4 studies that enrolled 326 mothers for maternal TAF therapy, resulting in 0% of MTCT and 0% infant malformation. All studies observed that TDF or TAF maternal therapy reduced MTCT rates significantly without safety concerns when compared with untreated groups, except for 1 RCT that failed the therapeutic endpoint. CONCLUSIONS: TDF is well established for preventing MTCT in highly viremic mothers, whereas TAF may become an option as data emerges.

mTORC2 acts as a gatekeeper for mTORC1 deficiency-mediated impairments in ILC3 development.

Group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function. Recent studies have investigated the role of the mammalian target of rapamycin complex (mTOR) in ILC3s, whereas the mTORC1-related mechanisms and crosstalk between mTORC1 and mTORC2 involved in regulating ILC3 homeostasis remain unknown. In this study, we found that mTORC1 but not mTORC2 was critical in ILC3 development, IL-22 production, and ILC3-mediated intestinal homeostasis. Single-cell RNA sequencing revealed that mTORC1 deficiency led to disruption of ILC3 heterogeneity, showing an increase in differentiation into ILC1-like phenotypes. Mechanistically, mTORC1 deficiency decreased the expression of NFIL3, which is a critical transcription factor responsible for ILC3 development. The activities of both mTORC1 and mTORC2 were increased in wild-type ILC3s after activation by IL-23, whereas inhibition of mTORC1 by Raptor deletion or rapamycin treatment resulted in increased mTORC2 activity. Previous studies have demonstrated that S6K, the main downstream target of mTORC1, can directly phosphorylate Rictor to dampen mTORC2 activity. Our data found that inhibition of mTORC1 activity by rapamycin reduced Rictor phosphorylation in ILC3s. Reversing the increased mTORC2 activity via heterozygous or homozygous knockout of Rictor in Raptor-deleted ILC3s resulted in severe ILC3 loss and complete susceptibility to intestinal infection in mice with mTORC1 deficiency (100% mortality). Thus, mTORC1 acts as a rheostat of ILC3 heterogeneity, and mTORC2 protects ILC3s from severe loss of cells and immune activity against intestinal infection when mTORC1 activity is diminished.

Validation of Baveno VII criteria for recompensation in entecavir-treated patients with hepatitis B-related decompensated cirrhosis.

BACKGROUND & AIMS: Antiviral therapy improves the clinical outcomes of patients with chronic hepatitis B (CHB), including those with cirrhosis. In the present study, we validated the Baveno VII definition of recompensation and explored the criteria for stable improvement of liver function tests in entecavir-treated patients with CHB-related decompensated cirrhosis. METHODS: In this multicentre prospective study, patients with decompensated (ascites) CHB-related cirrhosis were enrolled and treated with entecavir for 120 weeks. Patients were followed up for clinical events, viral and biochemical tests, and ultrasonography every 6 months. The recompensation rate per Baveno VII criteria was calculated. Multivariate regression models were used to identify the predictors of recompensation. Finally, the criteria for stable improvement of liver function tests were explored. RESULTS: Of the 320 recruited patients, 283 completed the 120-week study, with 261/283 (92.2%) achieving HBV DNA levels <20 IU/ml and 171/283 (60.4%) achieving resolution of ascites, encephalopathy, and absence of recurrent variceal bleeding for at least 12 months. We identified model for end-stage liver disease <10 and/or liver function tests within Child-Pugh Class A (albumin >35 g/L, international normalised ratio <1.50 and total bilirubin <34 µmol/L) as the criteria for stable improvement of liver function tests. Accordingly, 56.2% (159/283) of patients fulfilled the Baveno VII definition of recompensation with a stable improvement of liver function tests defined by the current study. CONCLUSIONS: Our study defined the criteria for a stable improvement of liver function tests required by the Baveno VII definition of recompensation in patients with CHB-related decompensated cirrhosis on antiviral therapy. The criteria derived from this multicentre prospective study warrant further validation in patients with cirrhosis of other aetiologies. LAY SUMMARY: Decompensation of cirrhosis marks the point at which the liver is no longer able to function normally (and symptoms become apparent). Recently the idea of recompensation was proposed for individuals who may experience an improvement in liver function if the underlying cause of their liver disease is addressed (e.g. antivirals for viral cirrhosis). Herein, we show that over 50% of patients with hepatitis B-related decompensated cirrhosis treated with antivirals could recompensate and we propose laboratory criteria which could be used to define recompensation.

Prenatal inflammation exposure-programmed hypertension exhibits multi-generational inheritance via disrupting DNA methylome.

The multi-generation heredity trait of hypertension in human has been reported, but the molecular mechanisms underlying multi-generational inheritance of hypertension remain obscure. Recent evidence shows that prenatal inflammatory exposure (PIE) results in increased incidence of cardiovascular diseases, including hypertension. In this study we investigated whether and how PIE contributed to multi-generational inheritance of hypertension in rats. PIE was induced in pregnant rats by intraperitoneal injection of LPS or Poly (I:C) either once on gestational day 10.5 (transient stimulation, T) or three times on gestational day 8.5, 10.5, and 12.5 (persistent stimulation, P). Male offspring was chosen to study the paternal inheritance. We showed that PIE, irrespectively induced by LPS or Poly (I:C) stimulation during pregnancy, resulted in multi-generational inheritance of significantly increased blood pressure in rat descendants, and that prenatal LPS exposure led to vascular remodeling and vasoconstrictor dysfunction in both thoracic aorta and superior mesenteric artery of adult F2 offspring. Furthermore, we revealed that PIE resulted in global alteration of DNA methylome in thoracic aorta of F2 offspring. Specifically, PIE led to the DNA hypomethylation of G beta gamma (Gßγ) signaling genes in both the F1 sperm and the F2 thoracic aorta, and activation of PI3K/Akt signaling was implicated in the pathologic changes and dysregulated vascular tone of aortic tissue in F2 LPS-P offspring. Our data demonstrate that PIE reprogrammed DNA methylome of cells from the germline/mature gametes contributes to the development of hypertension in F2 PIE offspring. This study broadens the current knowledge regarding the multi-generation effect of the cumulative early life environmental factors on the development of hypertension.

Study on the biological mechanism of urolithin a on nasopharyngeal carcinoma in vitro.

CONTEXT: Urolithin A (UroA) can inhibit the growth of many human cancer cells, but it has not be reported if UroA inhibits nasopharyngeal carcinoma (NPC) cells. OBJECTIVE: To explore the inhibitory effect of UroA on NPC and potential mechanism in vitro. MATERIALS AND METHODS: RNA-sequencing-based mechanistic prediction was conducted by comparing KEGG enrichment of 40 µM UroA-treated for 24 h with untreated CNE2 cells. The untreated cells were selected as control. After NPC cells were treated with 20-60 µM UroA, proliferation, migration and invasion of were measured by colony formation, wound healing and transwell experiments. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) were measured by flow cytometry, Hoechst 33342, Rhodamine 123, JC-1 staining and ROS assay methods, respectively. Gene and protein expression were measured by RT-qPCR and Western blotting assay. RESULTS: RNA-sequencing and KEGG enrichment revealed UroA mainly altered the ECM receptor interaction pathway. UroA inhibited cells proliferation, epithelial-mesenchymal-transition pathway, migration and invasion with IC50 values of 34.72 µM and 44.91 µM, induced apoptosis, MMP depolarization and increase ROS content at a concentration of 40 µM. UroA up-regulated E-cadherin, Bax/Bcl-2, c-caspase-3 and PARP proteins, while inhibiting COL4A1, MMP2, MMP9, N-cadherin, Vimentin and Snail proteins at 20-60 µM. Moreover, co-treatment of UroA (40 µM) and NAC (5 mM) could reverse the effect of UroA on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: RNA-sequencing technology based on bioinformatic analyses may be applicable for studiying the mechanism of drugs for tumour treatment.

The Efficacy of Proton Pump Inhibitor in Cirrhotics with Variceal Bleeding: A Systemic Review and Meta-Analysis.

BACKGROUND AND AIMS: Proton pump inhibitor (PPI) was widely used in cirrhotic patients with variceal bleeding empirically rather than evidence-based practice. We aimed to evaluate the plausible indication of PPI use in variceal bleeding cirrhotic patients and figure out whether it can decrease the re-bleeding rate after endoscopic therapy. Furthermore, we also investigated the association between PPI and bleeding-related mortality in these patients. METHODS: We have searched in PubMed, Medline, Web of Science, Google Scholar, Cochrane and Embase prior to May 2019. Pooled OR and 95% CI were calculated by random-effects model. RESULTS: A total of 11 original articles including 1,818 cirrhotic patients were analyzed. The overall meta-analysis highlighted that PPI use may decrease the re-bleeding rate after endoscopic therapy (OR 0.52, 95% CI 0.35-0.77). The conclusion was irrespective of study methods, endoscopic purpose and hemorrhage sites. However, the conclusion speculated that PPI should be prescribed >1 month. Meanwhile, PPI use may not impact the bleeding-related mortality. CONCLUSIONS: PPI, used for >1 month, can decrease re-bleeding rate after endoscopic therapy in cirrhotic patients for prophylaxis or emergency treatment purpose. No matter how long it takes, PPI use is not associated with bleeding-related mortality.

Lymph Node Metastasis Prediction from Primary Breast Cancer US Images Using Deep Learning.

Background Deep learning (DL) algorithms are gaining extensive attention for their excellent performance in image recognition tasks. DL models can automatically make a quantitative assessment of complex medical image characteristics and achieve increased accuracy in diagnosis with higher efficiency. Purpose To determine the feasibility of using a DL approach to predict clinically negative axillary lymph node metastasis from US images in patients with primary breast cancer. Materials and Methods A data set of US images in patients with primary breast cancer with clinically negative axillary lymph nodes from Tongji Hospital (974 imaging studies from 2016 to 2018, 756 patients) and an independent test set from Hubei Cancer Hospital (81 imaging studies from 2018 to 2019, 78 patients) were collected. Axillary lymph node status was confirmed with pathologic examination. Three different convolutional neural networks (CNNs) of Inception V3, Inception-ResNet V2, and ResNet-101 architectures were trained on 90% of the Tongji Hospital data set and tested on the remaining 10%, as well as on the independent test set. The performance of the models was compared with that of five radiologists. The models' performance was analyzed in terms of accuracy, sensitivity, specificity, receiver operating characteristic curves, areas under the receiver operating characteristic curve (AUCs), and heat maps. Results The best-performing CNN model, Inception V3, achieved an AUC of 0.89 (95% confidence interval [CI]: 0.83, 0.95) in the prediction of the final clinical diagnosis of axillary lymph node metastasis in the independent test set. The model achieved 85% sensitivity (35 of 41 images; 95% CI: 70%, 94%) and 73% specificity (29 of 40 images; 95% CI: 56%, 85%), and the radiologists achieved 73% sensitivity (30 of 41 images; 95% CI: 57%, 85%; P = .17) and 63% specificity (25 of 40 images; 95% CI: 46%, 77%; P = .34). Conclusion Using US images from patients with primary breast cancer, deep learning models can effectively predict clinically negative axillary lymph node metastasis. Artificial intelligence may provide an early diagnostic strategy for lymph node metastasis in patients with breast cancer with clinically negative lymph nodes. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Bae in this issue.

Acid suppression therapy and its association with spontaneous bacterial peritonitis incidence: A systemic review and meta-analysis.

AIM: It is well known that the use of proton pump inhibitor (PPI) is widespread in patients with liver cirrhosis. PPI counteracts H2 receptor inhibitor (H2 RA) with its strong acid suppression effect. However, there is always a concern that PPI use may increase spontaneous bacteria peritonitis (SBP) development in cirrhotic patients. We aimed to investigate the association between acid suppression therapy (i.e. PPI or H2 RA) and SBP through meta-analysis. METHODS: We searched PubMed, Medline, Web of Science, Cochrane library, and Embase for relevant studies published up to April 2019. Pooled OR and 95% CI were calculated by a random-effects model. Funnel plots and Egger's tests were performed for the evaluation of publication bias. Non-parametric "trim-and-fill" tests were conducted for sensitivity analysis. RESULTS: A total of 20 original articles including 9566 cirrhotic patients were analyzed. The overall meta-analysis highlighted that PPI use was associated with the risk of SBP (pooled OR 1.77, 95% CI 1.49-2.11). The conclusion was irrespective of study methods, whereas the result was inconsistent only in South America. However, the conclusion might not be stable enough and should be extrapolated with caution. Unlike PPI, we found H2 RA was not associated with SBP (pooled OR 1.06, 95% CI 0.75-1.48). CONCLUSIONS: In conclusion, PPI use, but not H2 RA, will increase the incidence of SBP in cirrhotic patients. In addition, H2 RA might be beneficial for patients who require long-term acid suppression therapy.

Prognostic impact of neutrophil-to-lymphocyte ratio in cirrhosis: A propensity score matching analysis with a prespecified cut-point.

BACKGROUND & AIMS: An elevated neutrophil-to-lymphocyte ratio (NLR) has received attention as a prognostic surrogate across chronic liver diseases. However, an exact threshold has not been fully elucidated. METHODS: A total number of 589 patients with cirrhosis (LC) were included. The value of NLR was calculated and its optimal cut-off was initially determined by X-tile program. Independent predictors of 90-day mortality were identified with Cox regression model. The Kaplan-Meier method was used to generate survival curves. To reduce influences of selection bias and possible confounders, a 1:2 propensity score matching (PSM) was performed. RESULTS: The X-tile indicated that the difference in survival was most significant for NLR more than 8.9. Serum NLR > 8.9 was an independent indicator in the entire cohort and PSM subset (HR 4.268, 95% CI 2.211-8.238, P < .001; HR 4.209, 95% CI 1.448-12.238, P = .008 respectively). Subgroup analysis showed that NLR > 8.9 was an independent risk factor of 90-day mortality regardless of age, gender, CTP or MELD score. CONCLUSIONS: The value of NLR more than 8.9 is a feasible cut-off across clinical settings among applicable population. The adding of NLR to other conventional predictive systems has the potential to provide incremental value without extra economic cost.