Deep Learning Radiomics Nomogram Based on Enhanced CT to Predict the Response of Metastatic Lymph Nodes to Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

BACKGROUND: We aimed to construct and validate a deep learning (DL) radiomics nomogram using baseline and restage enhanced computed tomography (CT) images and clinical characteristics to predict the response of metastatic lymph nodes to neoadjuvant chemotherapy (NACT) in locally advanced gastric cancer (LAGC). METHODS: We prospectively enrolled 112 patients with LAGC who received NACT from January 2021 to August 2022. After applying the inclusion and exclusion criteria, 98 patients were randomized 7:3 to the training cohort (n = 68) and validation cohort (n = 30). We established and compared three radiomics signatures based on three phases of CT images before and after NACT, namely radiomics-baseline, radiomics-delta, and radiomics-restage. Then, we developed a clinical model, DL model, and a nomogram to predict the response of LAGC after NACT. We evaluated the predictive accuracy and clinical validity of each model using the receiver operating characteristic curve and decision curve analysis, respectively. RESULTS: The radiomics-delta signature was the best predictor among the three radiomics signatures. So, we developed and validated a DL delta radiomics nomogram (DLDRN). In the validation cohort, the DLDRN produced an area under the receiver operating curve of 0.94 (95% confidence interval, 0.82-0.96) and demonstrated adequate differentiation of good response to NACT. Furthermore, the DLDRN significantly outperformed the clinical model and DL model (p < 0.001). The clinical utility of the DLDRN was confirmed through decision curve analysis. CONCLUSIONS: In patients with LAGC, the DLDRN effectively predicted a therapeutic response in metastatic lymph nodes, which could provide valuable information for individualized treatment.

Characteristics and survival of primary urothelial carcinoma of the prostate: A multi-center retrospective study of 18 cases.

OBJECTIVES: To explore the features, treatment, and outcomes of primary urothelial carcinoma of the prostate (PUCP) in a multicenter study. METHODS: The clinical and imaging features, pathological findings, treatment, and outcomes of patients diagnosed with PUCP from January 2011 to April 2022 at three institutions were collected and analyzed. The Kaplan-Meier method and log-rank test were used to assess survival rates of the overall group and survival differences between groups according to TNM stage. RESULTS: The study cohort comprised 18 patients with PUCP of mean age 72.4±7.8 years. Dysuria and urinary frequency were the most common symptoms (77.8 %). Sixteen (88.9 %) patients had normal serum total PSA concentrations. Most patients showed abnormalities on urinalysis. MRI was the most accurate diagnostic imaging method (88.9 %). As to immunohistochemistry findings, GATA-3 (81.8 %) and P63 (84.6 %) were positive in most examined patients; however, no lesions were positive for PSA. Three (17.6 %) patients with T1N0M0 and T2N0M0 tumors underwent radical cystectomy. Eleven (64.7 %) patients which almost all had T4 tumors received systematic therapy, most of them receiving chemotherapy with gemcitabine and cisplatin, and radiotherapy. The median overall survival was 42 months, and the median progression-free survival 25 months, the latter being significantly longer in patients with T1-2 than in those with T3-4 disease (p=0.035). CONCLUSION: PUCP, a rare but highly aggressive type of prostate cancer, should be considered in men with abnormalities on MRI and normal serum PSA concentrations. Positive GATA-3, P63, and negative PSA are typical immunohistochemistry features. Radical cystectomy and systematic therapies can be effective.

Illuminated fulvic acid stimulates denitrification and As(III) immobilization in flooded paddy soils via an enhanced biophotoelectrochemical pathway.

Fulvic acid (FA) is a representative photosensitive dissolved organic matter (DOM) compound that occurs naturally in paddy soils. In this study, the effect of a FA + nitrate treatment (0, 4 and 8 mg/L FA + 20 mmol/L nitrate) on denitrification and As(III) immobilization in flooded paddy soils was assessed under dark and intermittently illuminated conditions (12 h light+12 h dark). The FA input stimulated denitrification in illuminated soils (~100 % of nitrate removal within 6 days) compared to dark conditions (~92 % nitrate removal after 6 days). Meanwhile, As(III) (initial concentration of 0.1 mmol/L) was nearly completely immobilized (~100 %) under illuminated conditions after 4 days for the FA + nitrate treatment compared to 90- 93 % retention in the dark. Denitrification and As immobilization were positively related to the FA dosage in the illuminated assays. The stronger denitrification in illuminated soils was ascribed to denitrifiers harvesting photoelectrons from photosensitive substrates/semiconducting minerals. FA addition also increased the activities of denitrifying enzymes (e.g., NAR, NIR and NOR) and the denitrification electron transport system by nearly 0.6-0.7 and 1.5-1.8 times that of the nitrate-alone treatment under illuminated and dark conditions, thereby fostering stronger denitrification. Upon irradiation, As(III) immobilization was not only stimulated by the interactions with the denitrification pathway whereby As(III) acts as an electron donor for denitrifiers, but was also modulated by Fe(III)/oxidative reactive species-derived photooxidation of As(III). Moreover, the FA + nitrate treatment promoted the enrichment of metal-oxidizing bacteria (e.g., Stenotrophomonas and Acidovorax) that are responsible for nitrate-dependent As(III)/Fe(II) oxidation. The results of this study enhance our understanding of interactions among the biogeochemical cycles of As, Fe, N and C, which are intricately linked by a biophotoelectrochemical pathway in flooded paddy soils.

Nonadditive integration of visual information in ensemble processing.

Statistically summarizing information from a stimulus array into an ensemble representation (e.g., the mean) improves the efficiency of visual processing. However, little is known about how the brain computes the ensemble statistics. Here, we propose that ensemble processing is realized by nonadditive integration, rather than linear averaging, of individual items. We used a linear regression model approach to extract EEG responses to three levels of information: the individual items, their local interactions, and their global interaction. The local and global interactions, representing nonadditive integration of individual items, elicited rapid and independent neural responses. Critically, only the neural representation of the global interaction predicted the precision of the ensemble perception at the behavioral level. Furthermore, spreading attention over the global pattern to enhance ensemble processing directly promoted rapid neural representation of the global interaction. Taken together, these findings advocate a global, nonadditive mechanism of ensemble processing in the brain.

Event-triggered control of flexible manipulator constraint system modeled by PDE.

The vibration suppression control of a flexible manipulator system modeled by partial differential equation (PDE) with state constraints is studied in this paper. On the basis of the backstepping recursive design framework, the problem of the constraint of joint angle and boundary vibration deflection is solved by using the Barrier Lyapunov function (BLF). Moreover, based on the relative threshold strategy, an event-triggered mechanism is proposed to save the communication workload between controller and actuator, which not only deals with the state constraints of the partial differential flexible manipulator system, but also effectively improves the system work efficiency. Good damping effect on vibration and the elevated system performance can be seen under the proposed control strategy. At the same time, the state can meet the constraints given in advance, and all system signals are bounded. The proposed scheme is effective, which is proven by simulation results.

Incremental value of radiomics-based heterogeneity to the existing risk criteria in predicting recurrence of hepatocellular carcinoma after liver transplantation.

OBJECTIVES: The aim of the study was to evaluate the association between the radiomics-based intratumoral heterogeneity (ITH) and the recurrence risk in hepatocellular carcinoma (HCC) patients after liver transplantation (LT), and to assess its incremental to the Milan, University of California San Francisco (UCSF), Metro-Ticket 2.0, and Hangzhou criteria. METHODS: A multicenter cohort of 196 HCC patients were investigated. The endpoint was recurrence-free survival (RFS) after LT. A CT-based radiomics signature (RS) was constructed and assessed in the whole cohort and in the subgroups stratified by the Milan, UCSF, Metro-Ticket 2.0, and Hangzhou criteria. The R-Milan, R-UCSF, R-Metro-Ticket 2.0, and R-Hangzhou nomograms which combined RS and the four existing risk criteria were developed respectively. The incremental value of RS to the four existing risk criteria in RFS prediction was evaluated. RESULTS: RS was significantly associated with RFS in the training and test cohorts as well as in the subgroups stratified by the existing risk criteria. The four combined nomograms showed better predictive capability than the existing risk criteria did with higher C-indices (R-Milan [training/test] vs. Milan, 0.745/0.765 vs. 0.677; R-USCF vs. USCF, 0.748/0.767 vs. 0.675; R-Metro-Ticket 2.0 vs. Metro-Ticket 2.0, 0.756/0.783 vs. 0.670; R-Hangzhou vs. Hangzhou, 0.751/0.760 vs. 0.691) and higher clinical net benefit. CONCLUSIONS: The radiomics-based ITH can predict outcomes and provide incremental value to the existing risk criteria in HCC patients after LT. Incorporating radiomics-based ITH in HCC risk criteria may facilitate candidate selection, surveillance, and adjuvant trial design. KEY POINTS: • Milan, USCF, Metro-Ticket 2.0, and Hangzhou criteria may be insufficient for outcome prediction in HCC after LT. • Radiomics allows for the characterization of tumor heterogeneity. • Radiomics adds incremental value to the existing criteria in outcome prediction.

Optimized Pinecone-Squama-Structure MoS2-Coated CNT and Graphene Framework as Binder-Free Anode for Li-Ion Battery with High Capacity and Cycling Stability.

Extensive research has been conducted on the development of high-rate and cyclic stability anodes for lithium batteries (LIBs) due to their high energy density. Molybdenum disulfide (MoS2) with layered structure has garnered significant interest due to its exceptional theoretic Li+ storage behavior as anodes (670 mA h g-1). However, achieving a high rate and long cyclic life of anode materials remains a challenge. Herein, we designed and synthesized a free-standing carbon nanotubes-graphene (CGF) foam, then presented a facile strategy to fabricate the MoS2-coated CGF self-assembly anodes with different MoS2 distributions. Such binder-free electrode possesses the advantages of both MoS2 and graphene-based materials. Through rational regulation of the ratio of MoS2, the MoS2-coated CGF with uniformly distributed MoS2 exhibits a nano pinecone-squama-like structure that can accommodate the large volume change during the cycle process, thereby significantly enhancing the cycling stability (417 mA h g-1 after 1000 cycles), ideal rate performance, and high pseudocapacitive behavior (with a 76.6% contribution at 1 mV s-1). Such a neat nano-pinecone structure can effectively coordinate MoS2 and carbon framework, providing valuable insights for the construction of advanced anode materials.

A comparative study of modern total ankle replacement and ankle arthrodesis for ankle osteoarthritis at different follow-up times: a systematic review and meta-analysis.

PURPOSE: Total ankle replacement (TAR) or ankle arthrodesis (AA) is the main surgical treatment for end-stage ankle osteoarthritis. However, the therapeutic effect of the two surgical procedures at different follow-up times remains controversial. The purpose of this meta-analysis is to compare the short-term, medium-term, and long-term safety and efficiency of the two modern surgical treatments. METHODS: We conducted a comprehensive search in PubMed, EMBASE, Cochrane library databases, Web of Science, and Scopus. The main results were the patient's reported outcome measure (PROM) score, satisfaction, complications, reoperation, and surgery success rate. Different follow-up times and implant designs were used to evaluate the source of heterogeneity. We used a fixed effects model for meta-analysis and I2 statistic for evaluating heterogeneity. RESULTS: Thirty-seven comparative studies were included. In the short term, TAR significantly improved clinical scores (AOFAS score: WMD = 7.07, 95% Cl: 0.41-13.74, I2 = 0.0%; SF-36 PCS score: WMD = 2.40, 95% Cl: 2.22-2.58, I2 = 0.0%; SF-36 MCS score: WMD = 0.40, 95% Cl: 0.22-0.57, I2 = 0.0%; VAS for pain: WMD = - 0.50, 95% Cl: - 0.56-0.44, I2 = 44.3%) and had the lower incidence of revision (RR = 0.43, 95% CI: 0.23-0.81, I2 = 0.0%) and complications (RR = 0.67, 95% Cl: 0.50-0.90, I2 = 0.0%). In the medium term, there were still higher improvements in both the clinical scores (SF-36 PCS score: WMD = 1.57, 95% Cl: 1.36-1.78, I2 = 20.9%; SF-36 MCS score: WMD = 0.81, 95% Cl: 0.63-0.99, I2 = 48.8%) and the patient satisfaction (RR = 1.24, 95% Cl: 1.08-1.41, I2 = 12.1%) in the TAR group, but its total complications rate (RR = 1.84, 95% Cl: 1.26-2.68, I2 = 14.9%) and revision rate (RR = 1.58, 95% CI: 1.17-2.14, I2 = 84.6%) were significantly higher than that of the AA group. In the long term, there was no significant difference in clinical score and satisfaction, and a higher incidence of revision (RR = 2.32, 95% Cl: 1.70-3.16, I2 = 0.0%) and complications (RR = 3.18, 95% Cl: 1.69-5.99, I2 = 0.0%) was observed in TAR than in AA. The result of the third-generation design subgroup was consistent with that of the above pooled results. CONCLUSION: TAR had advantages over AA in the short term due to better performance in terms of PROMs, complications, and reoperation rates, but its complications become a disadvantage in the medium term. In the long term, AA seems to be favored because of lower complications and revision rates, although there is no difference in clinical scores.

Dynamics analysis of the anterior cruciate ligament reconstruction surgery based on magnetic resonance imaging.

In clinical practice, anterior cruciate ligament (ACL) rupture is always repaired by the single-beam reconstruction method. Before the surgery, the surgeon made the diagnosis based on medical images, such as CT (computerized tomography) and MR (magnetic resonance) images. However, little is known about how biomechanics governs the biological nature for femoral tunnel position. In the present study, three volunteers' motion trails were captured by six cameras when they were doing squat movement. The medical image can reconstruct the structure of the ligaments and bones and a left knee model was reconstructed by MIMICS by MRI data of DICOM format. Finally, the effects of different femoral tunnel positions on ACL biomechanics were characterized by the inverse dynamic analysis method. The results showed that there were significant differences in the direct mechanical effects of the anterior cruciate ligament at different locations of the femoral tunnel (p < 0.05), the peak stress of ACL in the low tension area was 1097.24 ± 25.55 N, and the peak stress of ACL in the distal femur was 356.81 ± 15.39 N, both of which were much higher than that in the direct fiber area (118.78 ± 20.68 N).

Subcortical encoding of summary statistics in humans.

Statistical encoding compresses redundant information from multiple items into a single summary metric (e.g., mean). Such statistical representation has been suggested to be automatic, but at which stage it is extracted is unknown. Here, we examined the involvement of the subcortex in the processing of summary statistics. We presented an array of circles dichoptically or monocularly while matching the number of perceived circles after binocular fusion. Experiments 1 and 2 showed that interocularly suppressed, invisible circles were automatically involved in the summary statistical representation, but only when they were presented to the same eye as the visible circles. This same-eye effect was further observed for consciously processed circles in Experiment 3, in which the estimated mean size of the circles was biased toward the information transmitted by monocular channels. Together, we provide converging evidence that the processing of summary statistics, an assumed high-level cognitive process, is mediated by subcortical structures.

Effects of outdoor artificial light at night on human health and behavior: A literature review.

The quality of life of human beings has improved tremendously through improved productivity, convenience, safety, and livability due to nighttime lights that illuminate outdoor work, leisure, and mobility. Recently, however, concerns have been growing over outdoor artificial light at night (ALAN) and its effects on human beings as well as ecosystems including animals and plants. This literature review aims to deliver a critical overview of the findings and the areas for future research on the effects of outdoor ALAN on human health and behaviors. Through a narrative literature review, we found that scientific research crucially lacks studies on the effects of outdoor ALAN on human behaviors and health, including social interaction, which may be more widespread compared to what is recognized so far. This review also highlights the importance of investigating the causal and complex relationships between outdoor ALAN, health, and behaviors with sleep as a key mediating factor. We elucidate that outdoor ALAN has both positive and negative effects on human life. Therefore, it is important for societies to be able to access facts and evidence about these effects to plan, agree to, and realize the optimal usage of nighttime lighting that balances its merits and demerits. Researchers in related areas of study must investigate and deliver the science of outdoor ALAN to various stakeholders, such as citizens, policymakers, urban and landscape planners, relevant practitioners, and industries. We believe that our review improves the understanding of outdoor ALAN in relation to human life and contributes to sustainable and thriving societies.

Rheological and fracturing characteristics of a cationic guar gum.

Guar gum (GG) fracturing fluid is frequently used in the field of enhanced oil recovery. GG fracturing fluids must have increased the temperature resistance and salt tolerance due to the complexity of drilled formations. In this study, the cationic guar gum (GG-GTA) samples for fracturing fluids were successfully synthesized, which can even resist 120 °C. It can be directly prepared by formation water, even sea water. Besides hydrogen bonds and covalent bonds, the additional cationic groups can strengthen the network even more in the GG-GTA fracturing fluids, which is why the GG-GTA fracturing fluids had stronger rheological properties than the GG fracturing fluids. The GG-GTA fracturing fluids performed well in terms of temperature resistance, salt tolerance, pressure resistance, and proppant carrying capacity. In addition, the GG-GTA gel-breaking caused little damage to core permeability because it exhibited low viscosity, interfacial tension, and surface tension. These results provide a solid foundation for the application of GG-GTA fracturing fluids in oilfield production.

An MRI-Based Radiomics Nomogram to Assess Recurrence Risk in Sinonasal Malignant Tumors.

BACKGROUND: Sinonasal malignant tumors (SNMTs) have a high recurrence risk, which is responsible for the poor prognosis of patients. Assessing recurrence risk in SNMT patients is a current problem. PURPOSE: To establish an MRI-based radiomics nomogram for assessing relapse risk in patients with SNMT. STUDY TYPE: Retrospective. POPULATION: A total of 143 patients with 68.5% females (development/validation set, 98/45 patients). FIELD STRENGTH/SEQUENCE: A 1.5-T and 3-T, fat-suppressed fast spin echo (FSE) T2-weighted imaging (FS-T2WI), FSE T1-weighted imaging (T1WI), and FSE contrast-enhanced T1WI (T1WI + C). ASSESSMENT: Three MRI sequences were used to manually delineate the region of interest. Three radiomics signatures (T1WI and FS-T2WI sequences, T1WI + C sequence, and three sequences combined) were built through dimensional reduction of high-dimensional features. The clinical model was built based on clinical and MRI features. The Ki-67-based and tumor-node-metastasis (TNM) model were established for comparison. The radiomics nomogram was built by combining the clinical model and best radiomics signature. The relapse-free survival analysis was used among 143 patients. STATISTICAL TESTS: The intraclass/interclass correlation coefficients, univariate/multivariate Cox regression analysis, least absolute shrinkage and selection operator Cox regression algorithm, concordance index (C index), area under the curve (AUC), integrated Brier score (IBS), DeLong test, Kaplan-Meier curve, log-rank test, optimal cutoff values. A P value < 0.05 was considered statistically significant. RESULTS: The T1 + C-based radiomics signature had best prognostic ability than the other two signatures (T1WI and FS-T2WI sequences, and three sequences combined). The radiomics nomogram had better prognostic ability and less error than the clinical model, Ki-67-based model, and TNM model (C index, 0.732; AUC, 0.765; IBS, 0.185 in the validation set). The cutoff values were 0.2 and 0.7 and then the cumulative risk rates were calculated. DATA CONCLUSION: A radiomics nomogram for assessing relapse risk in patients with SNMT may provide better prognostic ability than the clinical model, Ki-67-based model, and TNM model. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 5.

Genomic Insights into the Increased Occurrence of Campylobacteriosis Caused by Antimicrobial-Resistant Campylobacter coli.

Campylobacter is the leading bacterial cause of diarrheal illnesses worldwide. Campylobacter jejuni and C. coli are the most common species accounting for campylobacteriosis. Although the proportion of campylobacteriosis caused by C. coli is increasing rapidly in China, the underlying mechanisms of this emergence remain unclear. In this study, we analyzed the whole-genome sequences and associated environments of 1,195 C. coli isolates with human, poultry, or porcine origins from 1980 to 2021. C. coli isolates of human origin were closely related to those from poultry, suggesting that poultry was the main source of C. coli infection in humans. Analysis of antimicrobial resistance determinants indicated that the prevalence of multidrug-resistant C. coli has increased dramatically since the 2010s, coinciding with the shift in abundance from C. jejuni to C. coli in Chinese poultry. Compared with C. jejuni, drug-resistant C. coli strains were better adapted and showed increased proliferation in the poultry production environment, where multiple antimicrobial agents were frequently used. This study provides an empirical basis for the molecular mechanisms that have enabled C. coli to become the dominant Campylobacter species in poultry; we also emphasize the importance of poultry products as sources of campylobacteriosis caused by C. coli in human patients. IMPORTANCE The proportion of campylobacteriosis caused by C. coli is increasing rapidly in China. Coincidentally, the dominant species of Campylobacter occurring in poultry products has shifted from C. jejuni to C. coli. Here, we analyzed the whole-genome sequences of 1,195 C. coli isolates from different origins. The phylogenetic relationship among C. coli isolates suggests that poultry was the main source of C. coli infection in humans. Further analysis indicated that antimicrobial resistance in C. coli strains has increased dramatically since the 2010s, which could facilitate their adaptation in the poultry production environment, where multiple antimicrobial agents are frequently used. Thus, our findings suggest that the judicious use of antimicrobial agents could mitigate the emergence of multidrug-resistant C. coli strains and enhance clinical outcomes by restoring drug sensitivity in Campylobacter.

Depth of field and resolution-enhanced integral imaging display system.

Depth of field (DOF) and resolution are mutually restricted in integral imaging (II) display. To overcome the trade-offs, we propose an II display system that simultaneously enhances the DOF and resolution. The system consists of a transmissive mirror device (TMD), a semi-transparent mirror (STM), and two II display units. Each II display unit consists of a 4K display screen and a micro-lens array (MLA). Benefiting from the parallel placement of the TMD and the STM, two central depth planes are reconstructed, which effectively enhances the DOF. Meanwhile, the resolution in the overlapping DOF region is increased to two times due to the interpolation of the light field information from two II display units. The impact of the distance between the two II display units and the TMD on the 3D image quality is analyzed. In geometric optics, a distance between the II two display units and the TMD is optimized to eliminate ghost images. In wave optics, a distance is optimized to eliminate 3D pixel gaps by exploiting the diffraction effect of the TMD. Both the geometric and wave optics are considered simultaneously to obtain a high-quality 3D image without ghost images and 3D pixel gaps. A DOF and resolution-enhanced II display system is developed, and the experimental results verify its feasibility.

Development and validation of a nomogram to predict anastomotic leakage in colorectal cancer based on CT body composition.

Background: Anastomotic leakage (AL) is one of the most serious postoperative complications. This study aimed to investigate the predictive value of preoperative body composition for AL in patients with colorectal cancer (CRC). Methods: We first reviewed data from 3,681 patients who underwent radical CRC resection 2013-2021 in our hospital, and 60 patients were diagnosed with AL after surgery. We designed a nested case-control study and two controls were randomly selected for each case according to the time and position of surgery. Body composition was measured at the level of the third lumbar vertebra based on computed tomography (CT) images. The risk factors of AL were analyzed by univariate and multivariate analysis. Nomogram was built using binary regression analysis and assessed for clinical usefulness, calibration, and discrimination. Results: In the multivariate analysis, gender, blood glucose, nutrition risk screening (NRS), skeletal muscle area (SMA) and visceral fat area (VFA) were independent risk factors for developing anastomotic leakage after surgery. The prognostic model had an area under the receiver operating characteristic curve of 0.848 (95% CI, 0.781-0.914). The calibration curve showed good consistency between the predicted and observed outcomes. Decision curve analysis indicated that patients with colorectal cancer can benefit from the prediction model. Conclusions: The nomogram that combined with gender, blood glucose, NRS, SMA, and VFA had good predictive accuracy and reliability to AL. It may be conveniently for clinicians to predict AL preoperatively and be useful for guiding treatment decisions.

Effect of melatonin on quality of life and symptoms in patients with cancer: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: This study systematically reviewed the effect of melatonin (MLT) on quality of life (QoL) and symptoms among patients with cancer. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane Library, PubMed, Embase, Web of Science, Medline, CINAHL, Scopus, ClinicalTrials.gov, China Biology Medicine (CBM), ProQuest and Open Grey were searched from inception to November 2021. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) assessing the effects of MLT on QoL, sleep quality, fatigue, depression, pain, stomatitis rate and stomatitis severity in adult patients with cancer, without language restrictions. Studies that reported the effects of MLT along with other interventions and had incomplete or absent outcome data were excluded. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data, and another two reviewers assessed the risk of bias. The risk of bias for each eligible study was assessed using the Cochrane assessment tool. The mean difference or standard mean difference (SMD) with 95% CIs was used in the computation of continuous variables to synthesise data. The relative risk was used for dichotomous outcomes. Heterogeneity was assessed and quantified (I2 statistic). RESULTS: A total of 19 qualified studies that included 2101 patients with cancer (MLT: 1078, control: 1023) were included in the meta-analysis. The results indicated that MLT had no significant effect on QoL (SMD=-0.01, 95% CI (-0.14 to 0.11), p=0.83), sleep quality (SMD=-0.18, 95% CI (-0.62 to 0.26), p=0.42), fatigue (SMD=-0.34, 95% CI (-0.73 to 0.06), p=0.10), pain (SMD=-0.34, 95% CI (-0.7 to 0.02), p=0.06) or stomatitis severity (RR=0.78, 95% CI (0.47 to 1.30), p=0.35). MLT reduced stomatitis rate among patients with cancer (RR=0.47, 95% CI (0.26 to 0.88), p=0.02), except those with head and neck cancer (RR=1.09, 95% CI (0.92 to 1.29), p=0.35). MLT eased depression in patients who received administration for more than 14 days (SMD=-0.14, 95% CI (-0.27 to -0.01), p=0.03) and those who underwent surgery (SMD=-0.17, 95% CI (-0.32 to -0.03), p=0.02). CONCLUSION: The findings showed that MLT did not improve the QoL, sleep quality, fatigue, pain or stomatitis severity among patients with cancer. It had a limited effect on decreasing the stomatitis rate and easing depression. Different treatments, durations and cancer types were the main sources of heterogeneity. Further large-scale RCTs are urgently needed. In addition, the effects of different combinations of MLT dosage and duration, administration types and joint measures are worthy of further study. PROSPERO REGISTRATION NUMBER: CRD42021292855.

Role of precipitants in transition of acute decompensation to acute-on-chronic liver failure in patients with HBV-related cirrhosis.

Background & Aims: Pre-acute-on-chronic liver failure (ACLF) is a distinct intermediate stage between acute decompensation (AD) and ACLF. However, identifying patients with pre-ACLF and predicting progression from AD to ACLF is difficult. This study aimed to identify pre-ACLF within 28 days, and to develop and validate a prediction model for ACLF in patients with HBV-related decompensated cirrhosis. Methods: In total, 1,736 patients with HBV-related cirrhosis and AD were enrolled from 2 large-scale, multicenter, prospective cohorts. ACLF occurrence within 28 days, readmission, and 3-month and 1-year outcomes were collected. Results: Among 970 patients with AD without ACLF in the derivation cohort, the 94 (9.6%) patients with pre-ACLF had the highest 3-month and 1-year LT-free mortality (61.6% and 70.9%, respectively), which was comparable to those with ACLF at enrollment (57.1% and 67.1%); the 251 (25.9%) patients with unstable decompensated cirrhosis had mortality rates of 22.4% and 32.1%, respectively; while the 507 (57.9%) patients with stable decompensated cirrhosis had the best outcomes (1-year mortality rate of 2.6%). Through Cox proportional hazard regression, specific precipitants, including hepatitis B flare with HBV reactivation, spontaneous hepatitis B flare with high viral load, superimposed infection on HBV, and bacterial infection, were identified to be significantly associated with ACLF occurrence in the derivation cohort. A model that incorporated precipitants, indicators of systemic inflammation and organ injuries reached a high C-index of 0.90 and 0.86 in derivation and validation cohorts, respectively. The optimal cut-off value (0.22) differentiated high-risk and low-risk patients, with a negative predictive value of 0.95. Conclusions: Three distinct clinical courses of patients with AD are validated in the HBV-etiology population. The precipitants significantly impact on AD-ACLF transition. A model developed by the precipitant-systemic inflammation-organ injury framework could be a useful tool for predicting ACLF occurrence. Clinical trial number: NCT02457637 and NCT03641872. Lay summary: It was previously shown that patients with decompensated cirrhosis could be stratified into 3 groups based on their short-term clinical prognoses. Herein, we showed that this stratification applies to patients who develop cirrhosis as a result of hepatitis B virus infection. We also developed a precipitant-based model (i.e. a model that incorporated information about the exact cause of decompensation) that could predict the likelihood of these patients developing a very severe liver disease called acute-on-chronic liver failure (or ACLF).