The prognostic value of dynamic changes in SII for the patients with STEMI undergoing PPCI.

BACKGROUND: Predicting the prognosis of primary percutaneous coronary intervention(PPCI) in ST-segment elevation myocardial infarction (STEMI) patients in the perioperative period is of great clinical significance. The inflammatory response during the perioperative period is also an important factor. This study aimed to investigate the dynamic changes in the systemic immune inflammatory index (SII) during the perioperative period of PPCI and evaluate its predictive value for in-hospital and out-of-hospital outcomes in patients with STEMI. METHODS: This retrospective study included 324 consecutive patients with STEMI who were admitted to the cardiac care unit. Blood samples were collected before PPCI, 12 h (T1), 24 h, 48 h after PPCI, the last time before hospital discharge (T2), and 1 month after hospital discharge. The SII was calculated as (neutrophils×platelets)/lymphocytes. Based on whether the primary endpoint occurred, we divided the patients into event and non-event groups. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors that might influence the occurrence of the primary endpoint. Dynamic curves of SII were plotted, and receiver operating characteristic (ROC) curves were drawn for each node to calculate the optimal critical value, sensitivity, and specificity to assess their predictive ability for in-hospital and out-of-hospital courses. Kaplan-Meier curves were used to analyze the differences in survival rates at different SII inflammation levels. RESULTS: High levels of SII were individually related to the occurrence of the in-hospital period and long-term outcomes during the post-operative follow-up of STEMI patients (in-hospital SII: T1:OR 1.001,95%CI 1.001-1.001, P < 0.001; SII following hospital discharge: T1M: OR 1.008,95%CI 1.006-1.010, P < 0.001). Patients with high SII levels had lower survival rates than those with low SII levels. The analysis showed that the SII 12 h after (T1) and SII 1 month (T1M) had excellent predictive values for the occurrence of in-hospital and out-of-hospital outcomes, respectively (AUC:0.896, P < 0.001; AUC:0.892, P < 0.001). CONCLUSION: There is a significant relationship between the dynamic status of SII and prognosis in patients with STEMI. This study found that the 12 h and SII 1 month affected in-hospital and out-of-hospital outcomes, respectively. Consequently, we focused on the dynamic changes in the SII.

Characterization and analysis of dynamic changes of microbial community associated with grape decay during storage.

The rot caused by pathogens during the storage of table grapes is an important factor that affects the development of the grape industry and food safety, and it cannot be ignored. The development of innovative methods for pathogen control should be based on a comprehensive understanding of the overall microbial community changes that occur during grape storage. The study aims to investigate the relationship between the native microbiota (including beneficial, pathogenic and spoilage microorganisms) on grape surfaces and the development of disease during grape storage. In this study, the bacteria and fungi present on grape surfaces were analyzed during storage under room temperature conditions using high-throughput sequencing. During the storage of grapes at room temperature, observable diseases and a noticeable decrease in quality were observed at 8 days. Microbial community analysis showed that 4996 bacterial amplicon sequence variants (ASVs) and 488 fungal ASVs were determined. The bacterial richness exhibited an initial increase followed by a subsequent decrease. However, the diversity exhibited a distinct pattern of gradual decrease. The fungal richness and community diversity both exhibit a gradual decrease during the storage of grapes. Fungal ß-diversity analysis showed that despite the absence of rot and the healthy state of grapes on the first and fourth days, the fungal ß-diversity exhibited a significant difference. The analysis of changes in genera abundances suggested that Candidatus Profftella and Aspergillus exhibited dominance in the rotting grape at 16 days, which are the main pathogens that caused disease in the present study. The co-occurrence networks among the microbial showed that the Candidatus proftella genera has a positive correlation with Aspergillus niger, indicating that they work together to cause disease and promote growth in grapes. Predicting the function of bacterial communities found that the microorganisms associated with lipid metabolism at 4 days play an important role in the process of postharvest decay of grapes.

Genetic diversity and population divergence of Leonurus japonicus and its distribution dynamic changes from the last interglacial to the present in China.

BACKGROUND: Leonurus japonicus, a significant medicinal plant known for its therapeutic effects on gynecological and cardiovascular diseases, has genetic diversity that forms the basis for germplasm preservation and utilization in medicine. Despite its economic value, limited research has focused on its genetic diversity and divergence. RESULTS: The avg. nucleotide diversity of 59 accessions from China were 0.00029 and hotspot regions in petN-psbM and rpl32-trnL(UAG) spacers, which can be used for genotype discrimination. These accessions divided into four clades with significant divergence. The four subclades, which split at approximately 7.36 Ma, were likely influenced by the Hengduan Mountains uplift and global temperature drop. The initial divergence gave rise to Clade D, with a crown age estimated at 4.27 Ma, followed by Clade C, with a crown age estimated at 3.39 Ma. The four clades were not showed a clear spatial distribution. Suitable climatic conditions for the species were identified, including warmest quarter precipitation 433.20 mm ~ 1,524.07 mm, driest month precipitation > 12.06 mm, and coldest month min temp > -4.34 °C. The high suitability distribution showed contraction in LIG to LGM, followed by expansion from LGM to present. The Hengduan Mountains acted as a glacial refuge for the species during climate changes. CONCLUSIONS: Our findings reflected a clear phylogenetic relationships and divergence within species L. japonicus and the identified hotspot regions could facilitate the genotype discrimination. The divergence time estimation and suitable area simulation revealed evolution dynamics of this species and may propose conservation suggestions and exploitation approaches in the future.

Early gut microbiological changes and metabolomic changes in patients with sepsis: a preliminary study.

The gut microbiota is closely related to the development of sepsis. The aim of this study was to explore changes in the gut microbiota and gut metabolism, as well as potential relationships between the gut microbiota and environmental factors in the early stages of sepsis. Fecal samples were collected from 10 septic patients on the first and third days following diagnosis in this study. The results showed that in the early stages of sepsis, the gut microbiota is dominated by microorganisms that are tightly associated with inflammation, such as Escherichia-Shigella, Enterococcus, Enterobacteriaceae, and Streptococcus. On sepsis day 3 compared to day 1, there was a significant decrease in Lactobacillus and Bacteroides and a significant increase in Enterobacteriaceae, Streptococcus, and Parabacteroides. Culturomica_massiliensis, Prevotella_7 spp., Prevotellaceae, and Pediococcus showed significant differences in abundance on sepsis day 1, but not on sepsis day 3. Additionally, 2-keto-isovaleric acid 1 and 4-hydroxy-6-methyl-2-pyrone metabolites significantly increased on sepsis day 3 compared to day 1. Prevotella_7 spp. was positively correlated with phosphate and negatively correlated with 2-keto-isovaleric acid 1 and 3-hydroxypropionic acid 1, while Prevotella_9 spp. was positively correlated with sequential organ failure assessment score, procalcitonin and intensive care unit stay time. In conclusion, the gut microbiota and metabolites are altered during sepsis, with some beneficial microorganisms decreasing and some pathogenic microorganisms increasing. Furthermore, Prevotellaceae members may play different roles in the intestinal tract, with Prevotella_7 spp. potentially possessing beneficial health properties and Prevotella_9 spp. potentially playing a promoting role in sepsis.

Analysis of the dynamic changes in gut microbiota in patients with different severity in sepsis.

BACKGROUND: The gastrointestinal tract contains a massive microbiota, and targeting the gut could be a potential intervention for sepsis. However, the interaction between sepsis and the intestinal microbiota is defined as an "incompletely understood bidirectional relationship". METHODS: This retrospective observational cohort study investigated the fecal microbiota of sepsis patients admitted to the Department of Critical Care Medicine of the Central Hospital of Wuhan, China, from May 2019 to January 2020. 14 septic patients were divided into the non-severe group and the severe group according to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Herein, fecal samples were serially collected on admission, the third, fourth, and fifth days, and ICU discharge. The fecal microbiota was analyzed by 16S rRNA gene sequencing and its correlation with clinical parameters was evaluated. RESULTS: Bacteroidetes, Firmicutes, and Proteobacteria were dominant phyla at ICU admission, and fecal biodiversity was not significantly different between the non-severe group (APACHE II < 15) and the severe group (APACHE II > 15). However, the diversity of the gut microbiota was significantly lower at ICU discharge than that at ICU admission with the extension of treatment time. Further significant difference flora analysis (LEfSe) showed that the genera Veillonella and Ruminococcus were the most discriminant biomarkers at ICU admission in non-severe and severe patients, respectively, while Enterococcus was the most discriminant biomarker at ICU discharge in all septic patients. Of note, liver function tests, including ALT, AST, TBIL, and DBIL correlated with the prevalence of various bacterial genera. CONCLUSIONS: The diversity of the gut microbiota in patients with sepsis decreases dramatically during ICU stay, and there are distinct dynamic changes in gut microbiota among patients with different severity in sepsis.

The Logical Sequence of Primary Open Rhinoplasty Founded on the Principles of Rhinoplasty Dynamics.

Rhinoplasty is a perplexing procedure due to the variety of complex interplays between anatomical structures of the nose and the maneuvers used to accomplish the intended objective. Although every rhinoplasty is individualized, having a systematic order and an algorithm is crucial to achieve the designed aesthetic goals and a superior outcome, considering the interactions between maneuvers. Otherwise, the accumulated, unanticipated effects will result in displeasing outcomes due to over or under correction. In this report, we describe the sequential steps of rhinoplasty based on knowledge that the senior author has garnered over four decades of experience and having studied the rhinoplasty dynamics continually. Furthermore, we explain the detailed reasoning for each maneuver based on surgical indications and the resulting interplays.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Treatment of Acute Respiratory Distress Syndrome Caused by COVID-19 with Human Umbilical Cord Mesenchymal Stem Cells.

This study aimed to identify the impact of mesenchymal stem cell transplantation on the safety and clinical outcomes of patients with severe COVID-19. This research focused on how lung functional status, miRNA, and cytokine levels changed following mesenchymal stem cell transplantation in patients with severe COVID-19 pneumonia and their correlation with fibrotic changes in the lung. This study involved 15 patients following conventional anti-viral treatment (Control group) and 13 patients after three consecutive doses of combined treatment with MSC transplantation (MCS group). ELISA was used to measure cytokine levels, real-time qPCR for miRNA expression, and lung computed tomography (CT) imaging to grade fibrosis. Data were collected on the day of patient admission (day 0) and on the 7th, 14th, and 28th days of follow-up. A lung CT assay was performed on weeks 2, 8, 24, and 48 after the beginning of hospitalization. The relationship between levels of biomarkers in peripheral blood and lung function parameters was investigated using correlation analysis. We confirmed that triple MSC transplantation in individuals with severe COVID-19 was safe and did not cause severe adverse reactions. The total score of lung CT between patients from the Control and MSC groups did not differ significantly on weeks 2, 8, and 24 after the beginning of hospitalization. However, on week 48, the CT total score was 12 times lower in patients in the MSC group (p ≤ 0.05) compared to the Control group. In the MSC group, this parameter gradually decreased from week 2 to week 48 of observation, whereas in the Control group, a significant drop was observed up to week 24 and remained unchanged afterward. In our study, MSC therapy improved lymphocyte recovery. The percentage of banded neutrophils in the MSC group was significantly lower in comparison with control patients on day 14. Inflammatory markers such as ESR and CRP decreased more rapidly in the MSC group in comparison to the Control group. The plasma levels of surfactant D, a marker of alveocyte type II damage, decreased after MSC transplantation for four weeks in contrast to patients in the Control group, in whom slight elevations were observed. We first showed that MSC transplantation in severe COVID-19 patients led to the elevation of the plasma levels of IP-10, MIP-1α, G-CSF, and IL-10. However, the plasma levels of inflammatory markers such as IL-6, MCP-1, and RAGE did not differ between groups. MSC transplantation had no impact on the relative expression levels of miR-146a, miR-27a, miR-126, miR-221, miR-21, miR-133, miR-92a-3p, miR-124, and miR-424. In vitro, UC-MSC exhibited an immunomodulatory impact on PBMC, increasing neutrophil activation, phagocytosis, and leukocyte movement, activating early T cell markers, and decreasing effector and senescent effector T cell maturation.

Effects of rotation and Bacillus on the changes of continuous cropping soil fungal communities in American ginseng.

The continuous cropping obstacle is the main factor in leading to difficulty in American ginseng replanting. The dormant microbiota in the soil may be the cause of American ginseng disease and eventually caused continuous cropping obstacles, but there are few studies on the dynamic changes of soil microenvironment after American ginseng planting. In this study, we tracked short-term variation in physicochemical properties, enzyme activities, and fungal communities over time-series in soils with continuous cropping obstacle under crop rotation and probiotic Bacillus treatments. Furthermore, we examined the relationships between the important fungal compositions and the soil properties. The results showed that sucrase, cellulase, urease and acid phosphatase activities were significantly increased, while catalase and dehydrogenase were decreased with treatments time. Rotation treatment significantly affected the diversity, dissimilarity degree and species distribution of soil fungal community with continuous cropping obstacle over a short-term. Moreover, beneficial fungal biomarkers such as Cladorrhinum, Oidiodendron, and Mariannaea were accumulated at 48 h under rotation treatments. Almost all fungal biomarkers were negatively correlated with hydrolases and positively correlated with oxidoreductases and acid phosphatase under crop rotation treatments. This study suggested that compared to probiotic Bacillus, crop rotation can significantly affect soil fungal community structure, especially the enrichment of specific potentially beneficial fungal species. Our findings provide a scientific basis for understanding the dynamic changes of fungal communities and soil properties with continuous cropping obstacle of American ginseng in initial stage of soil improvement.

[Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia].

Objective: To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate (TAF) after treatment with entecavir (ETV) in patients with chronic hepatitis B (CHB) with low-level viremia (LLV). Methods: 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected. Patients were divided into a complete virologic response (CVR) group (n = 84) and a low-level viremia (LLV) group (n = 42) according to the HBV DNA level during treatment. Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis. Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks: continued use of ETV as a control group; replacement of TAF as a sequential group; and combination of ETV and TAF as a combined group. The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks. HBV DNA negative conversion rate, HBeAg negative conversion rate, alanine aminotransferase (ALT), creatinine (Cr), and liver stiffness test (LSM) were compared among the three groups after 96 weeks of antiviral treatment. Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients, and the Log-Rank test was used for comparison. HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically. Results: Univariate analysis showed statistically significant differences in age, BMI, HBeAg positivity rate, HBV DNA, HBsAg, ALT, AST, and LSM at baseline between the CVR group and the LLV group (P < 0.05). Univariate analysis of variance revealed no statistically significant difference among the three groups of LLV patients at 48 weeks (P > 0.05). HBV-DNA negative conversion rate in the sequential group and the combination group was significantly higher than that in the control group after 96 weeks of treatment (88.89% vs. 41.18%, 85.71% vs. 41.18%, χ (2) = 10.404, P = 0.006). HBeAg negative conversion rate was higher than that of the control group, with no statistically significant difference (P > 0.05).Compared with the control group, ALT, Cr, and LSM in the sequential group and the combined group were equally improved to varying degrees, with a statistically significant difference (P < 0.05). Subsequent use of ETV and HBV DNA at 48 weeks were independent risk factors for HBV DNA positivity at 96 weeks in LLV patients (P < 0.05). The AUC of HBV DNA at 48 weeks was 0.735 (95%CI: 0.578 ~ 0.891), the cut-off value was 2.63 log(10) IU/ml, and the sensitivity and specificity were 76.90% and 72.40%, respectively. DNA conversion rate was significantly lower in LLV patients receiving 48-week ETV and 48-week HBV DNA≥2.63 log10 IU/mL than in patients receiving sequential or combined TAF and 48-week HBV DNA < 2.63 log(10) IU/mL. HBV DNA negative conversion rates in the sequential group and combined group at 72 weeks, 84 weeks, and 96 weeks were higher than those in the control group during the period from 48 weeks to 96 weeks of continuous treatment, and the differences were statistically significant (P < 0.05). Conclusion: Sequential or combined TAF antiviral therapy could more effectively improve the 96-week CVR rate, as well as hepatic and renal function, and alleviate the degree of hepatic fibrosis in CHB patients with LLV following ETV treatment. Subsequent use of ETV and HBV DNA load at 48 weeks were independent predictors of HBV DNA positivity at 96 weeks in LLV patients.

Longitudinal changes of blood parameters and weight in inoperable stage III NSCLC patients treated with concurrent chemoradiotherapy followed by maintenance treatment with durvalumab.

BACKGROUND: Investigating dynamic changes in blood-parameters and weight in patients with locally advanced non-small cell lung cancer (NSCLC) receiving durvalumab maintenance therapy after chemoradiotherapy (cCRT). Laboratory outcomes were determined based on the number of durvalumab administrations received. METHODS: Twenty-two patients completed platinum-based cCRT followed by maintenance treatment with durvalumab. Different parameters such as hemoglobin (Hb), leukocytes, Lactate dehydrogenase (LDH), C-reactive protein (CRP), body weight and albumin were analyzed before cCRT, after cCRT, 3, 6, 9 and 12 months after starting durvalumab maintenance. RESULTS: Sixteen (72.7%) patients were male; twelve (54.5%) and fifteen (68.2%) patients had non-squamous histology and Union for International Cancer Control (UICC) stage IIIB-C disease, respectively. Median follow-up time was 24.4 months; 12- and 18-months- progression-free and overall-survival rates were 55.0% and 45.0 as well as 90.2 and 85.0%, respectively. During maintenance treatment Hb increased by 1.93 mg/dl (17.53%) after 9 months (p < 0.001) and 2.02 mg/dl (18.46%) after 12 months compared to the start of durvalumab (p < 0.001). LDH decreased by 29.86 U/l (- 11.74%) after 3 months (p = 0.022). Receipt of at least 12 cycles of durvalumab was beneficial in terms of Hb-recovery (Hb 6 months: 12.64 vs. 10.86 [mg/dl]; Hb 9 months: 13.33 vs 11.74 [mg/dl]; (p = 0.03)). Median weight change [kilogram (kg)] was + 6.06% (range: - 8.89 - + 18.75%) after 12 months. The number of durvalumab cycles significantly correlated with total weight gain [kg] (Spearman-Rho-correlation: r = 0.502*). CONCLUSION: In the investigated cohort, no severe hematologic toxicity occurred by laboratory blood tests within 1 year of durvalumab maintenance therapy after cCRT for unresectable stage III NSCLC. Receiving at least 12 cycles of durvalumab appears to have a significant effect on recovery of hemoglobin levels and body weight.

Tiller Angle Control 1 Is Essential for the Dynamic Changes in Plant Architecture in Rice.

Plant architecture is dynamic as plants develop. Although many genes associated with specific plant architecture components have been identified in rice, genes related to underlying dynamic changes in plant architecture remain largely unknown. Here, we identified two highly similar recombinant inbred lines (RILs) with different plant architecture: RIL-Dynamic (D) and RIL-Compact (C). The dynamic plant architecture of RIL-D is characterized by 'loosetiller angle (tillering stage)-compact (heading stage)-loosecurved stem (maturing stage)' under natural long-day (NLD) conditions, and 'loosetiller angle (tillering and heading stages)-loosetiller angle and curved stem (maturing stage)' under natural short-day (NSD) conditions, while RIL-C exhibits a compact plant architecture both under NLD and NSD conditions throughout growth. The candidate locus was mapped to the chromosome 9 tail via the rice 8K chip assay and map-based cloning. Sequencing, complementary tests, and gene knockout tests demonstrated that Tiller Angle Control 1 (TAC1) is responsible for dynamic plant architecture in RIL-D. Moreover, TAC1 positively regulates loose plant architecture, and high TAC1 expression cannot influence the expression of tested tiller-angle-related genes. Our results reveal that TAC1 is necessary for the dynamic changes in plant architecture, which can guide improvements in plant architecture during the modern super rice breeding.

Dynamic change of neutrophil-to-lymphocyte ratio and symptomatic intracerebral hemorrhage after endovascular recanalization therapy.

OBJECTIVES: The neutrophil-to-lymphocyte ratio (NLR) is a known marker of systemic inflammation. Recent studies demonstrated its applicability as a marker of poor prognosis for stroke patients. In this study, we evaluated the relationship between dynamic changes in the NLR and sICH in patients with successful recanalization following ERT. MATERIALS AND METHODS: This study included 128 patients with acute ischemic stroke who underwent successful ERT between January 2013 and November 2019. We evaluated the NLR pre-ERT (at admission) and post-ERT (at 24-36 h after ERT). The symptomatic ICH and miserable outcomes at 3 months after ERT were analyzed as outcomes. sICH was defined as type-2 parenchymal hematoma with neurological deterioration (defined as National Institute of Health Stroke Scale score ≥4). Moreover, a modified Rankin Scale score of 5-6 at 3 months was considered a miserable outcome. RESULTS: Among the included patients, sICH occurred in 12 (9.4%). The sICH group had significantly higher post-ERT NLR (P < 0.001) and ∆NLR (calculated as the difference between pre-ERT NLR and post-ERT NLR) (P = 0.004). In the multivariate analysis, the post-ERT NLR was independently associated with sICH (odds ratio [OR], 1.166; 95% confidence interval [CI], 1.041-1.306; P = 0.008) and miserable outcome at 3 months (OR, 1.101; 95% CI, 1.002-1.210; P = 0.045). CONCLUSIONS: This study demonstrated that temporal elevation of the NLR is associated with sICH events after successful ERT in patients with acute ischemic stroke. The temporal variation in NLR may help to identify high-risk patients with sICH after ERT.

The dynamic changes of serum IgM and IgG against SARS-CoV-2 in patients with COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide pandemic since it emerged in December 2019. Previous studies have reported rapid antibody response to SARS-CoV-2 in the first 2 to 3 weeks after symptom onset. Here, we retrospectively described the dynamic changes of serum immunoglobulin M (IgM) and IgG specifically against SARS-CoV-2 in later weeks (mainly 4-10 weeks) in 97 hospitalized patients with COVID-19. We observed that serum IgM and IgG, especially in patients with moderate-to-high levels, declined significantly between week 4 to 10 after illness onset. Notably, IgG levels in high percentage of patients (77.5%, 31 of 40) rapidly declined by half, from 212.5 (range, 163.7-420.3) to 96.3 (range, 75.0-133.4) AU/mL, within 1 to 2 weeks in the second month and then sustained at around 100 AU/mL until discharge from hospital. Significant reduction of IgM was also observed as SARS-CoV-2 nucleic acid turned negative (P = .002). In the recovery stage, serum IgG declined significantly (early vs late recovery stage, n = 16, P = .003) with a median reduction of 50.0% (range, 3.7%-77.0%). Our results suggested that the decline of IgM may be an indicator of virus clearance and recovered patients may have a robust immunity against reinfection within at least 3 months after illness onset. Yet, the rapid reduction of IgG by half rises serious concerns on the robustness and sustainability of the humoral immune response in the period after discharge, which is crucial for immunity strategy and developing a vaccine.

Development of a simple dynamic algorithm for individualized hepatocellular carcinoma risk-based surveillance using pre- and post-treatment general evaluation score.

BACKGROUND AND AIMS: With the growing number of treated hepatitis C patients, the current 'one-size-fits-all' hepatocellular carcinoma (HCC) surveillance strategies for patients with advanced fibrosis represents a great burden on healthcare systems. An individualized HCC risk strategy incorporates the dynamic changes of HCC risk are lacking. METHODS: This single-centre observational study included 3075 patients, with advanced fibrosis (≥F3) who achieved SVR following DAAs at Egyptian Liver research institute and hospital (ELRIAH) with follow-up period (range 6-72 months). The performance of a recently developed General Evaluation Score (GES) HCC risk stratification score was calculated pre- and post-treatment using Harrell's c statistic. Times to HCC and cumulative incidences were calculated with Kaplan-Meier method and compared using log-rank (Mantel-Cox) test. RESULTS: Pre-treatment GES score stratified patients into low (60.4%), intermediate (23.4%), and (16.2%) high-risk score where 5-year cumulative incidences of HCC were 1.66%, 4.45% and 7.64%, respectively. Harrell's c statistic was 0.801. Post-treatment GES score stratified patients into low (57.4%), intermediate (30.7%) and (11.9%) high-risk score where 5-year cumulative incidences of HCC were 1.35%, 3.49% and 11.09% respectively. The cumulative HCC incidence increased significantly with higher scores (P < .001). Harrell's c statistic was 0.818. Using pre- and post-treatment GES score, GES algorithm was developed with higher predictive value. The cumulative HCC incidence increased significantly with higher scores (P < .001). Harrell's c statistic was 0.832. CONCLUSION: A dynamic algorithm incorporating both pre- and post-GES scores have better performance and predictive value compared with only pre-treatment assessments. The proposed algorithm would help to stratify those who need intensive or being excluded from screening.

Kinetics of the neutrophil-lymphocyte ratio during PD-1 inhibition as a prognostic factor in advanced hepatocellular carcinoma.

BACKGROUND AND AIMS: Programmed death 1 (PD-1) inhibitors have improved survival outcomes and produced durable responses in advanced hepatocellular carcinoma (HCC) for some patients. Here, we evaluated the relationship between the baseline and kinetics of the neutrophil-lymphocyte ratio (NLR) and clinical outcomes in nivolumab-treated HCC patients. METHODS: All consecutive HCC patients treated with nivolumab between July 2017 and June 2020 were screened for the eligibility. The NLRs were calculated before and at 2, 4 and 6 weeks after treatment. Survival outcomes were compared based on the baseline and kinetics of NLR. We additionally analysed the association of the baseline and dynamic changes in the NLR with hyperprogression (HPD). RESULTS: Among the 194 included cases, most patients were male (82.0%) and had a Child-Pugh Class A disease (70.6%). Patients with a baseline NLR ≥ 3 (hazard ratio [HR] 2.46; 95% CI 1.63-3.71) had a poorer overall survival than patients with baseline NLR < 3. During the treatment, the NLR increased rapidly in patients developing HPD, and only a ΔNLR at 4 weeks was predictive of HPD. The risk of HPD increased by 20% for every 20% increase in the ΔNLR at 4 weeks. Accordingly, an NLR increase at 4 weeks (HR 1.79; 95% CI 1.19-2.68) was associated with an increased risk of death, especially among patients with a baseline NLR ≥ 3. CONCLUSIONS: The baseline and on-treatment kinetics for the NLR are effective prognostic indicators in nivolumab-treated patients with HCC. This may help to guide patient selection and on-treatment strategies for immunotherapies in advanced HCC.

Prognostic importance of dynamic changes in systemic inflammatory markers for patients with gastric cancer.

PURPOSE: To investigate the effect of dynamic changes in systemic inflammatory markers (SIM) on long-term prognosis of patients with gastric cancer (GC). METHODS: A retrospective analysis was performed on the data of 2180 patients with GC who underwent radical gastrectomy in the Fujian medical university Union Hospital from January 2009 to December 2014. Changes in SIM between preoperatively and 1-6 months and 12 months postoperatively were reported. RESULTS: In multivariate analysis, higher preoperative systemic inflammation score (pre-SIS) was independent predictor of poor prognosis (p < 0.05). The optimal time of remeasurement was 12 months postoperatively, based on a longitudinal profile of SIS and accuracy in predicting 5-year overall survival (OS) (area under the curve: 0.712 [95% confidence interval: 0.630-0.785]). According to the association between the conversion of SIS and OS, we classified patients into three risk groups. Kaplan-Meier curves showed significant differences in OS among risk groups. Further Cox multivariate regression analysis showed that only risk groups of SIS and pTNM stage were independent prognostic factors for OS. CONCLUSION: The efficacy of SIS in predicting prognosis 12 months after surgery is superior, and the elevation of SIS 12 months after surgery predicts poor prognosis.

Dynamic changes in lymphocyte subsets and parallel cytokine levels in patients with severe and critical COVID-19.

BACKGROUND: The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis. METHODS: A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected. RESULTS: On admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells. CONCLUSIONS: A sustained decrease in lymphocyte subsets, especially CD4+ T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.

Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study.

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.

An unusual ECG change after a car crash.

A 34-year-old male patient was preparing for splenic artery embolization because of a car crash. Personal or family histories of cardiovascular diseases, sudden cardiac death, or Brugada syndrome were denied. Type 1 Brugada pattern was observed in the preoperative electrocardiogram and gradually resolved within a week. Chest blunt trauma may contribute to the transient ECG changes, and some particular considerations should be taken in this patient.

Lifestyle coaches as a central professional in the health care network? Dynamic changes over time using a network analysis.

BACKGROUND: Overweight and obesity are problems that are increasing globally in both children as well as adults, and may be prevented by adopting a healthier lifestyle. Lifestyle coaches counsel overweight and obese children (and their parents) as well as adults in initiating and maintaining healthier lifestyle behaviours. It is currently unclear whether this novel professional in the Dutch health care system functions as a linchpin in networks that evolve around lifestyle-related health problems. The aim of the present study is to investigate the formation and development of networks of lifestyle coaches and their positions within these networks. METHODS: In this longitudinal study, key professionals and professionals within relevant organisations in the Coaching on Lifestyle (CooL) care networks were asked to fill in three online questionnaires. Respondents were asked to indicate whether they collaborated with each of the specified professionals in the context of CooL. The overall network structures and the central role of the lifestyle coaches were examined by using network analysis. RESULTS: The results showed that the networks in three out of four regions were relatively centralised, but that none of the networks were dense, and that the professionals seemed to collaborate less with others over time. Half of the lifestyle coaches had a high number of collaborations and a central position within their networks, which also increased over time. In half of the regions, the lifestyle coaches had increased their role as consultants, while their role as gatekeeper and liaison decreased over time. In most regions, the sector of lifestyle coaches had a central position in their networks in just one measurement. Other central sectors were the local sports organisation, public health services, youth health care and the municipal government. CONCLUSIONS: Overall, we cannot conclude that more central and denser networks were formed during the study period. In addition, the lifestyle coaches were not often positioned as a central sector within these networks. Entrepreneurial, network and brokering competences are required for lifestyle coaches to build up denser networks. TRIAL REGISTRATION: NTR6208 ; date registered: 13-01-2017; retrospectively registered; Netherlands Trial Register.