Prognosis of patients with coexisting obesity and malnutrition after ischemic stroke: A cohort study.

BACKGROUND: The double burden of malnutrition, defined as the coexistence of obesity and malnutrition, is an increasing global health concern and is unclear in patients after ischemic stroke. The current study explored the combined impacts of obesity and malnutrition on patients with ischemic stroke. METHODS: We conducted a single-center prospective cohort study with patients with ischemic stroke enrolled in Minhang Hospital in China between January 2018 and December 2022. Patients were stratified into four categories based on their obesity (defined by body mass index) and nutritional status (classified according to the Controlling Nutritional Status score): (1) nourished nonobese, (2) malnourished nonobese, (3) nourished obese, and (4) malnourished obese. The primary end points were poor outcomes and all-cause mortality at 3 months. RESULTS: A total of 3160 participants with ischemic stroke were included in our study, of which 64.7% were male and the mean age was 69 years. Over 50% of patients were malnourished. At 3-month follow-up, the malnourished nonobese had the worst outcomes (34.4%), followed by the malnourished obese (33.2%), nourished nonobese (25.1%), and nourished obese (21.8%; P < 0.001). In multivariable analyses, with nourished nonobese group as the reference, the malnourished nonobese group displayed poorer outcomes (odds ratio [OR], 1.395 [95% CI, 1.169-1.664], P < 0.001) and higher all-cause mortality (OR, 1.541 [95% CI, 1.054-2.253], P = 0.026), but only a nonsignificant increase in poor prognosis rate (33.2% vs. 25.1%, P = 0.102) and mortality (4.2% vs. 3.6%, P = 0.902) were observed in the malnourished obese group. CONCLUSION: A high prevalence of malnutrition is observed in the large population suffering from ischemic attack, even in the obese. Malnourished patients have the worst prognosis particularly in those with severe nutritional status regardless of obesity, while the best functional outcomes and the lowest mortality are demonstrated in nourished obese participants.

The systemic inflammation score is a prognostic factor for patients with ischemic stroke who have not undergone intravenous thrombolysis or endovascular thrombectomy therapy.

BACKGROUND: The systemic inflammation score (SIS) has been utilised as a representative biomarker for evaluating nutritional and inflammation status. However, the predictive value of SIS has not been reported in patients with acute ischemic stroke (AIS). We aimed to evaluate whether SIS is associated with prognosis in stroke. METHODS: A total of 4801 patients with AIS were included in the study. The primary outcome was a modified Rankin Scale score>2 at the 3-month follow-up. A total of 4801 patients were randomly allocated into training (n=3361) and validation cohorts (n=1440) at a ratio of 7:3. Model performance was validated using the receiver operating characteristic (ROC) curve and calibration curve. Additionally, a comparison was made between the nomogram and the THRIVE score in regards to their respective predictive capabilities. RESULTS: Overall, 1091(32.5%) patients in the training cohort and 446 (31.0%) patients in the validation cohort experienced an unfavorable outcome. The multivariate logistic regression analysis revealed that a high SIS, age, NIHSS, diabetes and prior stroke were associated with unfavorable outcome. Our nomogram was developed based on the variables mentioned above. The area under the curve (AUC) of the training set and the validation set are 0.702 and 0.708, respectively, indicating that the model has modest agreement and discrimination. The results of AUC, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) showed that nomogram had significantly higher predictive value than THRIVE scores (all P<0.001). However, unlike the THRIVE publication, all patients who had undergone intravenous thrombolysis or endovascular thrombectomy therapy were excluded in our study. In consequence, our derived THRIVE scores cannot be compared to those in the original THRIVE study. CONCLUSION: The SIS exhibits potential as a simple prognostic biomarker, and the nomogram, which utilizes the SIS, may serve as a valuable tool for clinicians in the early identification of patients at heightened risk for unfavorable outcomes.

Bile acid profiling as an effective biomarker for staging in pediatric inflammatory bowel disease.

Rapid and accurate clinical staging of pediatric patients with inflammatory bowel disease (IBD) is crucial to determine the appropriate therapeutic approach. This study aimed to identify effective, convenient biomarkers for staging IBD in pediatric patients. We recruited cohorts of pediatric patients with varying severities of IBD to compare the features of the intestinal microbiota and metabolites between the active and remitting disease stages. Metabolites with potential for staging were targeted for further assessment in both patients and colitis model mice. The performance of these markers was determined using machine learning and was validated in a separate patient cohort. Pediatric patients with IBD exhibited distinct gut microbiota structures at different stages of disease activity. The enterotypes of patients with remitting and active disease were Bacteroides-dominant and Escherichia-Shigella-dominant, respectively. The bile secretion pathway showed the most significant differences between the two stages. Fecal and serum bile acid (BA) levels were strongly related to disease activity in both children and mice. The ratio of primary BAs to secondary BAs in serum was developed as a novel comprehensive index, showing excellent diagnostic performance in stratifying IBD activity (0.84 area under the receiver operating characteristic curve in the primary cohort; 77% accuracy in the validation cohort). In conclusion, we report profound insights into the interactions between the gut microbiota and metabolites in pediatric IBD. Serum BAs have potential as biomarkers for classifying disease activity, and may facilitate the personalization of treatment for IBD.

Prediction of poststroke cognitive impairment based on the systemic inflammatory response index.

BACKGROUND: Poststroke cognitive impairment (PSCI) is a prevalent complication among stroke survivors. Although the systemic inflammatory response index (SIRI) has been shown to be a reliable predictor of a variety of inflammatory diseases, the association between the SIRI and PSCI is still unclear. Therefore, the purpose of this study was to investigate the relationship between SIRI and PSCI, and to design a nomogram to predict the risk of PSCI in acute ischemic stroke (AIS) patients. METHODS: A total of 1342 patients with AIS were included in the study. Using the Mini-Mental State Examination scale, patients were separated into PSCI and non-PSCI groups within 2 weeks of stroke. Clinical data and SIRI values were compared between the groups. We developed the optimal nomogram for predicting PSCI using multivariate logistic regression. Finally, the nomogram was validated using the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: In total, 690 (51.4%) patients were diagnosed with PSCI. After adjusting for potential confounders, the SIRI (OR = 1.226, OR: 1.095-1.373, p < .001) was shown to be an independent risk factor for PSCI in the logistic regression analysis. The nomogram based on patient gender, age, admission National Institutes of Health Stroke Scale scores, education, diabetes mellitus, and SIRI had good discriminative ability with an area under the curve (AUC) of 0.716. The calibration curve and Hosmer-Lemeshow test revealed excellent predictive accuracy for the nomogram. Finally, the DCA showed the good clinical utility of the model. CONCLUSION: Increased SIRI on admission is correlated with PSCI, and the nomogram built with SIRI as one of the predictors can help identify PSCI early.

High serum lactate dehydrogenase to albumin ratio is associated with increased risk of poor prognosis after ischemic stroke.

BACKGROUND: Lactate dehydrogenase to albumin ratio (LAR) is a comprehensive biomarker for anaerobiosis, inflammation, and nutritional status, but its prognostic value for ischemic stroke has rarely been reported. We aimed to prospectively investigate whether serum LAR is associated with the prognosis of ischemic stroke patients in a large-scale cohort study. MATERIALS AND METHODS: Serum LAR levels were measured among 6634 patients with ischemic stroke admitted at Minhang hospital from January 2018 to December 2022. The primary outcome was the composite of major disability and death (modified Rankin Scale score [mRS] ≥ 3) at 3-month follow up. Secondary outcomes included death and the ordered 7-level category score of mRS. Multivariate logistic regression and restricted cubic splines were adopted to evaluate the associations between serum LAR levels and adverse clinical outcomes of ischemic stroke. RESULTS: During 3 months of follow-up period, a total of 2125 patients experienced primary outcome. After multivariate adjustment, the highest quartile of serum LAR was associated with an increased risk of primary outcome (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.27-1.83; P for trend < 0.001). Each standard deviation higher log-transformed serum LAR resulted in a 20% (95% CI, 12%-28%) increased risk of primary outcome. Furthermore, multivariable-adjusted restricted cubic spline analyses showed a linear association between the serum LAR level with primary outcome (P for linearity < 0.001). Finally, the addition of serum LAR to conventional risk factors significantly improved risk predictive abilities for the primary outcome (net reclassification improvement [NRI]: 18.35%, P < 0.001; integrated discrimination improvement [IDI]: 0.35%, P < 0.001) at 3-month follow up in patients with ischemic stroke. CONCLUSION: High serum LAR level was independently associated with an increased risk of adverse clinical outcomes among patients with ischemic stroke, indicating that serum LAR may be a valuable prognostic biomarker for ischemic stroke.

Systematic identification and characterization of five transcription factors mediating the oxidative stress response in Candida albicans.

Candida albicans is an opportunistic human fungal pathogen that causes superficial and systemic infections, particularly in immunocompromised individuals. In response to C. albicans infection, innate immune cells of the host produce and accumulate reactive oxygen species (ROS), which can lead to irreversible damage and apoptosis of fungal cells. Several transcription factors involved in this oxidative stress response have been identified; however, a systematic study to identify the transcription factors that mediate the oxidative stress response has not yet been conducted. Here, we screened a comprehensive transcription factor mutant library consisting of 211 transcription factor deletion mutant strains in the presence and absence of hydrogen peroxide (H2O2), a potent ROS inducer, and identified five transcription factors (Skn7, Dpb4, Cap1, Dal81, and Stp2) that are sensitive to H2O2. Genome-wide transcriptional profiling revealed that H2O2 induces a discrete set of differentially regulated genes among the five identified transcription factor mutant strains. Functional enrichment analysis identified KEGG pathways pertaining to glycolysis/gluconeogenesis, amino sugar and nucleotide sugar metabolism, and ribosome synthesis as the most enriched pathways. GO term analysis of the top common differentially expressed genes among the transcription factor mutant strains identified hexose catabolism and iron transport as the most enriched GO terms upon exposure to H2O2. This study is the first to systematically identify and characterise the transcription factors involved in the response to H2O2. Based on our transcriptional profiling results, we found that exposure to H2O2 modulates several downstream genes involved in fungal virulence. Overall, this study sheds new light on the metabolism, physiological functions, and cellular processes involved in the H2O2-induced oxidative stress response in C. albicans.

Value of the stroke 1-2-0 prehospital stroke education system: the experience of a general practitioner team.

BACKGROUND: Stroke is one of the leading causes of death worldwide, especially in developing countries. In China, there is an urgent need to educate people about stroke awareness and the importance of using emergency medical services (EMS) quickly after a stroke has occurred. OBJECTIVE: We sought to explore the effects of the Stroke 1-2-0 Prehospital Stroke Education System based on the experience of a general practitioner team. METHOD: We prospectively enrolled 119 community general practitioners to be trained in the procedures advocated by the Stroke 1-2-0 Prehospital Stroke Education System. The training content included early detection of ischemic stroke, first aid for stroke, and intravenous thrombolysis; The effects of the training were later evaluated via a before-and-after comparison. The 119 enrolled physicians formed a Stroke 1-2-0 lecturer group and taught stroke knowledge to community residents. The group remained active for 6 months, during which the medical treatment data of stroke patients (i.e., stroke onset time, prehospital delay, whether an ambulance was called, and whether thrombolytic therapy was performed) in each of 5 jurisdictions were recorded for the month before (January 2021) and that after (August 2021) the 6-month community education program. Finally, the effects of the community education program were evaluated. RESULTS: The participants' understanding of intravenous thrombolysis in the treatment of acute ischemic stroke improved significantly after the training as compared with their earlier understanding (96% vs. 78.99%; P < .001), and their understanding of the time window for intravenous thrombolysis increased from 26.05% before to 72% (P < .001) after the training. Most of the participants (90% vs. 67.23%; P < .001) said that they would immediately call the 120 emergency number of China's emergency phone system if they encountered individuals who appeared to be victims of acute stroke. A total of 82 stroke patients were seen before and 67 after the community education program. As for the use of the emergency call system, more patients with stroke activated that system after the program versus before (21.95% vs. 37.31%; P = .04). The 3-hour arrival rate after the program was nearly three times higher than that before the program (62.69% vs. 19.51%; P < .001). Also, regarding receiving thrombolysis after the occurrence of a stroke, the program triggered a substantial increase compared with the total earlier (19.4% vs. 6.1%; P = .013). CONCLUSION: We found that the Stroke 1-2-0 Prehospital Stroke Education System significantly improved community residents' knowledge regarding stroke.

Early antithrombotic therapy in patients with postinterventional cerebral hyperdensity reduces early neurological deterioration after mechanical thrombectomy.

BACKGROUND: Initiation of early antithrombotic therapy after acute ischemic stroke (AIS) is crucial. We aimed to investigate whether early antithrombotic therapy influences early neurological deterioration (END) in AIS patients with postinterventional cerebral hyperdensity (PCHD) immediately after mechanical thrombectomy (MT). METHODS: We retrospectively analyzed 108 consecutive anterior circulation AIS patients with PCHD immediately after MT. All patients were divided into END group and non-END group and END was defined as an increase of four points or more on the postinterventional National Institutes of Health Stroke Scale (NIHSS) score within the first 72 h after MT. Early antithrombotic therapy was defined as patients with PCHD who received antithrombotic therapy within 24 h after MT. Statistical analyses were performed to evaluate the association between early antithrombotic therapy and the risk of END. RESULTS: Among 108 patients, 27 (25%) patients developed END. Multivariate regression analysis revealed that early use of antithrombotic therapy (OR = 0.229, 95%CI = 0.083-0.626, P = 0.004) was an independent protector of END and postinterventional low density shadow exceeding 1/3 of the vascular territory (OR = 4.000, 95%CI = 1.157-13.834, P = 0.029) was an independent risk factor for END. CONCLUSION: Antithrombotic therapy within 24 h after MT maybe associated with the reduced risk of END in anterior circulation AIS patients with PCHD.

The regulatory subunits of CK2 complex mediate DNA damage response and virulence in Candida Glabrata.

BACKGROUND: Candida glabrata which belongs to normal microbiota, has caused significant concern worldwide due to its high prevalence and drug resistance in recent years. C. glabrata has developed many strategies to evade the clearance of the host immune system, thereby causing persistent infection. Although coping with the induced DNA damage is widely acknowledged to be important, the underlying mechanisms remain unclear. RESULTS: The present study provides hitherto undocumented evidence of the importance of the regulatory subunits of CgCK2 (CgCkb1 and CgCkb2) in response to DNA damage. Deletion of CgCKB1 or CgCKB2 enhanced cellular apoptosis and DNA breaks and led to cell cycle delay. In addition, deficiencies in survival upon phagocytosis were observed in Δckb1 and Δckb2 strains. Consistently, disruption of CgCKB1 and CgCKB2 attenuated the virulence of C. glabrata in mouse models of invasive candidiasis. Furthermore, global transcriptional profiling analysis revealed that CgCkb1 and CgCkb2 participate in cell cycle resumption and genomic stability. CONCLUSIONS: Overall, our findings suggest that the response to DNA damage stress is crucial for C. glabrata to survive in macrophages, leading to full virulence in vivo. The significance of this work lies in providing a better understanding of pathogenicity in C. glabrata-related candidiasis and expanding ideas for clinical therapies.

High-Dose Vitamin C Alleviates Pancreatic Necrosis by Inhibiting Platelet Activation Through the CXCL12/CXCR4 Pathway in Severe Acute Pancreatitis.

Background: Platelet activation in the early stage of pancreatitis is the key step developing into pancreatic necrosis. Studies suggested that vitamin C (Vit C) can inhibit platelet activity by targeting CXCL12/CXCR4 pathway. High-dose Vit C were showed to reduce pancreatic necrosis in severe acute pancreatitis (SAP) but the mechanism remains unclear. Here we speculate high-dose Vit C reduce pancreatic necrosis by inhibiting platelet activation through downregulating CXCL12/CXCR4 pathway. Methods: The pancreatic microcirculation of rats was observed by intravital microscopy. The platelet activity of SAP rats treated with or without high-dose Vit C was analyzed by platelet function test. Besides, the activity of platelets preincubated with high-dose Vit C or vehicle from SAP patients was also evaluated. Then, the TFA (CXCR4 agonist) and rCXCL12 were used to neutralize the effect of high-dose Vit C in SAP rats treated with high-dose Vit C. Meanwhile, the levels of enzymes and inflammatory cytokines in rat plasma, and rats' pancreatic histopathology and mortality were assessed. Results: Platelets from animals and patients with SAP are more sensitive to agonists and are more easily activated. Administration of high-dose Vit C significantly ameliorated excessive activation of platelets in SAP rats, ultimately increasing the microvessel density and inducing microthrombus and blood stasis; these results were consistent with clinical sample analysis. Moreover, high-dose Vit C significantly inhibited the release of amylase, lipase, TNF-α, and IL-6 in SAP rat plasma, reducing pancreatic damage and the mortality of SAP rats. However, using TFA and rCXCL12 significantly reversed the effect of high-dose Vit C on excessive activation of platelets, aggravating microcirculation impairment and pancreatic damage. Conclusion: The present study suggests that high-dose Vit C can ameliorate pancreatic necrosis by improving microcirculation disorders of SAP. For the first time, the underlying mechanism is related with inhibiting platelet activation through the CXCL12/CXCR4 pathway.

Clostridioides difficile aggravates dextran sulfate solution (DSS)-induced colitis by shaping the gut microbiota and promoting neutrophil recruitment.

Clostridioides difficile is a pathogen contributing to increased morbidity and mortality of patients with inflammatory bowel disease (IBD). To determine how C. difficile affects the severity of colitis, we constructed a dextran sulfate solution-induced colitis model challenged with C. difficile. Without antibiotic administration, C. difficile led to transient colonization in mice with colitis, but still significantly enhanced disease severity as assessed by weight loss, histopathological damages, and inflammatory cytokine concentrations. Because this effect is independent of toxin production as shown by infection with a non-toxigenic strain, we focused on changes in the gut microbiota. The microbiota altered by C.difficile, featured with reduced proportions of g_Prevotellaceae_UCG-001 and g_Muribaculaceae, were confirmed to contribute to disease severity in colitis mice via fecal microbiota transplantations. The inflamed colon showed neutrophil accumulation by flow cytometric analysis and myeloperoxidase immunochemical staining. There was enrichment of upregulated genes in leukocyte chemotaxis or migration as shown by RNA sequencing analysis. The isolated neutrophils from C. difficile-infected mice with colitis showed a robust migratory ability and had enhanced expression of cytokines and chemokines. We observed a detrimental role of neutrophils in the progress of disease by hindering neutrophil recruitment with the CXCR2 inhibitor SB225002. Furthermore, neutrophil recruitment appeared to be regulated by interleukin (IL)-1ß, as inhibition of IL-1ß production by MCC950 markedly ameliorated inflammation with decreased neutrophil accumulation and neutrophil-derived chemokine expression. In conclusion, our study provides information on the complicated interaction between microbiota and immune responses in C. difficile-induced inflammation in mice with colitis. Our findings could help determine potential therapeutic targets for patients with IBD concurrent with C. difficile infection.

Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis.

BACKGROUND: The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application. METHOD: In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out. Finally, the above results were validated by the microbiome and transcriptomics analysis in an animal model of sepsis. RESULTS: Patients with sepsis showed destruction of symbiotic flora and elevated abundance of Enterococcus, which were validated in animal experiments. Additionally, patients with a high burden of Bacteroides, especially B. vulgatus, had higher Acute Physiology and Chronic Health Evaluation II scores and longer stays in the intensive care unit. The intestinal transcriptome in CLP rats illustrated that Enterococcus and Bacteroides had divergent profiles of correlation with differentially expressed genes, indicating distinctly different roles for these bacteria in sepsis. Furthermore, patients with sepsis exhibited disturbances in gut amino acid metabolism compared with healthy controls; namely, tryptophan metabolism was tightly related to an altered microbiota and the severity of sepsis. CONCLUSION: Alterations in microbial and metabolic features in the gut corresponded with the progression of sepsis. Our findings may help to predict the clinical outcome of patients in the early stage of sepsis and provide a translational basis for exploring new therapies.

Risk factors for small intestinal bacterial overgrowth in patients with acute ischaemic stroke.

Introduction. The intestinal flora has become a promising new target in acute ischaemic stroke (AIS), and small intestinal bacterial overgrowth (SIBO) is a common pathological condition of the intestinal flora. Recently, the lactose hydrogen-methane breath test has emerged as a non-invasive and economical method for the detection of SIBO in AIS patients. Exploring the prevalence of SIBO and its associated risk factors will provide a clinical basis for the association between intestinal flora and AIS.Hypothesis/Gap Statement. Given that the prevalence of SIBO and its risk factors in patients with AIS remain to be studied, there is a need to investigate them.Aim. This study aimed to investigate the prevalence and risk factors of SIBO in patients with AISMethodology. Eighty patients tested for SIBO using the lactulose hydrogen-methane breath test were evaluated. Patients were divided into SIBO-positive and SIBO-negative groups according to the presence or absence of SIBO, respectively. The baseline characteristics and clinical biochemical indicators of the patients were compared between the two groups. The independent risk factors and predictive value of SIBO in AIS patients were determined using multivariate logistic regression and receiver operating characteristic (ROC) curve analyses.Results. Of the 80 consecutive patients with AIS, 23 (28.8 %) tested positive for SIBO. Triglyceride (TG) and homocysteine (Hcy) levels were identified as independent risk factors for SIBO in patients with AIS using multivariate logistic regression analysis (P<0.005). ROC curve analysis showed that the area under the curve (AUC) of TG was 0.690 (95 % CI 0.577-0.789, P=0.002). The sensitivity, specificity and optimal cut-off values were 95.7 %, 35.1 % and 1.14 mmol l-1, respectively. The AUC of Hcy was 0.676 (95 % CI 0.562-0.776, P=0.01). The sensitivity, specificity and optimal cut-off values were 73.9 %, 59.7 % and 14.1 µmol-1, respectively. When TG and Hcy levels were combined, the AUC increased to 0.764 (95 % CI 0.656-0.852, P<0.001). The specificity and sensitivity were 61.4 and 82.6 %, respectively. This showed that the combined detection of TG and Hcy levels had a higher predictive valueConclusion. The prevalence of SIBO in patients with AIS was 28.8 %. TG and Hcy levels are independent risk factors for SIBO in patients with AIS. Both markers had good predictive value for the occurrence of SIBO. In the future, we should actively utilize these indicators to prevent intestinal flora imbalance and the occurrence of SIBO.

Systemic inflammation response index predicts 3-month outcome in patients with mild acute ischemic stroke receiving intravenous thrombolysis.

Introduction: A crucial aspect of stroke progression is the inflammatory response. As novel inflammatory and prognostic markers, the systemic immune inflammation index (SII) and the systemic inflammation response index (SIRI) have recently been studied. The objective of our study was to evaluate the prognostic value of SII and SIRI in mild acute ischemic stroke (AIS) patients following intravenous thrombolysis (IVT). Methods: Our study screened the clinical data of patients with mild AIS admitted to the Minhang Hospital of Fudan University for retrospective analysis. The SIRI and SII were examined by the emergency laboratory before IVT. Functional outcome was evaluated 3 months after the onset of stroke using the modified Rankin Scale (mRS). mRS ≥ 2 was defined as an unfavorable outcome. The relationship between SIRI and SII and the 3-month prognosis was determined using both univariate and multivariate analysis. Receiver operating characteristic curve was performed to evaluate the predictive value of SIRI for AIS prognosis. Results: A total of 240 patients were included in this study. Both SIRI and SII were higher in the unfavorable outcome group than in the favorable outcome group [1.28 (0.70-1.88) vs. 0.79 (0.51-1.08), P < 0.001 and 531.93 (377.55-797.12) vs. 397.23 (263.32-577.65), P < 0.001]. Multivariate logistic regression analyses showed that SIRI was significantly associated with 3-month unfavorable outcome of mild AIS patients [odds ratio (OR) = 2.938, 95% confidence interval (CI) = 1.805-4.782, P < 0.001], conversely, SII had no prognostic value. When SIRI combined with the established clinical factors, the area under the curve (AUC) showed a significant improvement (0.773 vs. 0.683, P for comparison = 0.0017). Conclusions: Higher SIRI could be valuable in predicting poor clinical outcomes for patients with mild AIS following IVT.

Systemic sclerosis with cerebral infarction and severe stenosis of internal carotid artery and coronary artery: A case report.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microangiopathy, extensive fibrosis and autoantibody production. It is generally believed that microvascular disease is the hallmark of SSc. Macrovascular involvement is not initially considered as a feature of SSc, but its mortality is high, which should not be ignored. Up to the present, SSc patients with cerebral involvement and multiple macrovascular stenosis have been rarely described. We herein report a case of cerebral infarction and severe stenosis of the internal carotid artery and coronary artery associated with SSc.

Numerical Study on the Influence of Model Uncertainties on the Transport of Underwater Spilled Oil.

Oil pollution influences marine biology, ecology, and regional sustainable development capacity, but model uncertainties limit the ability of the numerical model to accurately predict the transport and fate of the underwater oil spill. Based on a three-dimensional underwater oil spill model validated by satellite images of the oil slick at the sea surface, the Penglai 19-3 oil spill accident in the Bohai Sea was simulated; in addition, several sensitivity experiments were set up to investigate the influence of model uncertainties in the background wind, current, start time of the oil spill, and spill site on the transport of underwater spilled oil in the Penglai 19-3 oil spill accident. The experimental results indicate that the uncertainty in the background wind has a certain impact on the simulated centroid position at the sea surface, and little effect on the simulated underwater results, while the uncertainty in the background current has a significant influence on the transport of the underwater spilled oil both at the sea surface and underwater. An uncertainty of 24 h in the start time of the oil spill can cause more than 1 time larger than the benchmark case displacement of the oil spill centroid point and sweeping area at the sea surface, as the periodic tidal current is the main constituent of the ocean current in the Bohai Sea. The uncertainty in the spill site has a large influence on the final position of the oil spill centroid point, but the oil spill trajectories do not intersect with each other within 48 h, which makes it possible to identify the oil spill platform from the actual observations. The influence of uncertainties in the important model inputs and key model parameters on the transport of underwater spilled oil in the Penglai 19-3 oil spill accident is evaluated for the first time, which is of substantial significance for improving the prediction accuracy of the transport and fate of underwater oil spills.

Complete Genome Sequencing and Comparative Phenotypic Analysis Reveal the Discrepancy Between Clostridioides difficile ST81 and ST37 Isolates.

Toxin A-negative, toxin B-positive Clostridioides difficile strains, which primarily include the ST81 and ST37 genotypes, are predominant in C. difficile infections leading to antibiotic-associated diarrhea in China. Recently, ST81 has been reported as the most prevalent genotype rather than ST37, although the genetic and functional characteristics of the two genotypes remain ambiguous. In this study, we conducted comprehensive comparative analysis of these two genotypes through complete genome sequencing and phenotypic profiling. The whole genome sequencing revealed that the ST81 and ST37 isolates were closely related genetically with similar gene compositions, and high rate of the core genome shared. The integrative and conjugative elements identified in ST81 were similar to those in ST37, albeit with more diverse and insertion regions. By characterizing the phenotypes related to colonization or survival in the host, we found that the ST81 isolates exhibited robust colonization ability and survival both in vitro and in vivo, enhanced spore production, and slightly increased motility, which may be attributable to the discrepancy in non-synonymous single-nucleotide polymorphisms in the relevant functional genes. Furthermore, the ST81 isolates displayed a significantly higher rate of resistance to fluoroquinolones compared with the ST37 isolates (94.12% vs. 62.5%) and mostly carried the amino acid substitution Asp426Val in GyrB. In summary, the results of our study indicate that ST81 isolates exhibit enhanced ability to transmit between hosts and survive in harsh environments, providing key genetic insights for further epidemiological investigations and surveillance of C. difficile infection.

Short- and long-term outcomes associated with enhanced recovery after surgery protocol vs conventional management in patients undergoing laparoscopic gastrectomy.

BACKGROUND: At present, the enhanced recovery after surgery (ERAS) protocol is widely implemented in the field of gastric surgery. However, the effect of the ERAS protocol on the long-term prognosis of gastric cancer has not been reported. AIM: To compare the effects of ERAS and conventional protocols on short-term outcomes and long-term prognosis after laparoscopic gastrectomy. METHODS: We retrospectively analyzed the data of 1026 consecutive patients who underwent laparoscopic gastrectomy between 2012 and 2015. The patients were divided into either an ERAS group or a conventional group. The groups were matched in a 1:1 ratio using propensity scores based on covariates that affect cancer survival. The primary outcomes were the 5-year overall and cancer-specific survival rates. The secondary outcomes were the postoperative short-term outcomes and inflammatory indexes. RESULTS: The patient demographics and baseline characteristics were similar between the two groups after matching. Compared to the conventional group, the ERAS group had a significantly shorter postoperative hospital day (7.09 d vs 8.67 d, P < 0.001), shorter time to first flatus, liquid intake, and ambulation (2.50 d vs 3.40 d, P < 0.001; 1.02 d vs 3.64 d, P < 0.001; 1.47 d vs 2.99 d, P < 0.001, respectively), and lower medical costs ($7621.75 vs $7814.16, P = 0.009). There was a significantly higher rate of postoperative complications among patients in the conventional group than among those in the ERAS group (18.1 vs 12.3, P = 0.030). Regarding inflammatory indexes, the C-reactive protein and procalcitonin levels on postoperative day 3/4 were significantly different between the two groups (P < 0.001 and P = 0.025, respectively). The ERAS protocol was associated with significantly improved 5-year overall survival and cancer-specific survival rates compared with conventional protocol (P = 0.013 and 0.032, respectively). When stratified by tumour stage, only the survival of patients with stage III disease was significantly different between the two groups (P = 0.044). CONCLUSION: Adherence to the ERAS protocol improves both the short-term outcomes and the 5-year overall survival and cancer-specific survival of patients after laparoscopic gastrectomy.

Risk factors and intestinal microbiota: Clostridioides difficile infection in patients receiving enteral nutrition at Intensive Care Units.

BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of nosocomial diarrhea. Patients receiving enteral nutrition (EN) in the intensive care unit (ICU) are potentially at high risk of CDI. In the present study, we assessed the risk factors and intestinal microbiome of patients to better understand the occurrence and development of CDI. METHODS: Patients were screened for C. difficile every week after starting EN, and their clinical records were collected for risk factor identification. Fecal samples were analyzed using 16S rRNA sequencing to evaluate the intestinal microbiota. RESULTS: Overall incidence of CDI was 10.7% (18/168 patients). History of cerebral infarction was significantly associated with CDI occurrence (OR, 9.759; 95% CI, 2.140-44.498), and treatment with metronidazole was identified to be protective (OR, 0.287; 95% CI, 0.091-0.902). Patients with EN had lower bacterial richness and diversity, accompanied by a remarkable decrease in the abundance of Bacteroides, Prevotella_9, Ruminococcaceae, and Lachnospiraceae. Of these patients, acquisition of C. difficile resulted in a transient increase in microbial diversity, along with consistent alterations in the proportion of some bacterial taxa, especially Ruminococcaceae and Lachnospiraceae. Upon initiation of EN, patients who were positive for C. difficile later showed an enhanced load of Bacteroides, which was negatively correlated with the abundance of C. difficile when CDI developed. CONCLUSION: ICU patients receiving EN have a high prevalence of CDI and a fragile intestinal microbial environment. History of cerebral infarction and prior treatment with metronidazole are considered as vital risk and protective factors, respectively. We propose that the emergence of CDI could cause a protective alteration of the intestinal microbiota. Additionally, Bacteroides loads seem to be closely related to the occurrence and development of CDI.

Concordance Between Watson for Oncology and a Multidisciplinary Clinical Decision-Making Team for Gastric Cancer and the Prognostic Implications: Retrospective Study.

BACKGROUND: With the increasing number of cancer treatments, the emergence of multidisciplinary teams (MDTs) provides patients with personalized treatment options. In recent years, artificial intelligence (AI) has developed rapidly in the medical field. There has been a gradual tendency to replace traditional diagnosis and treatment with AI. IBM Watson for Oncology (WFO) has been proven to be useful for decision-making in breast cancer and lung cancer, but to date, research on gastric cancer is limited. OBJECTIVE: This study compared the concordance of WFO with MDT and investigated the impact on patient prognosis. METHODS: This study retrospectively analyzed eligible patients (N=235) with gastric cancer who were evaluated by an MDT, received corresponding recommended treatment, and underwent follow-up. Thereafter, physicians inputted the information of all patients into WFO manually, and the results were compared with the treatment programs recommended by the MDT. If the MDT treatment program was classified as "recommended" or "considered" by WFO, we considered the results concordant. All patients were divided into a concordant group and a nonconcordant group according to whether the WFO and MDT treatment programs were concordant. The prognoses of the two groups were analyzed. RESULTS: The overall concordance of WFO and the MDT was 54.5% (128/235) in this study. The subgroup analysis found that concordance was less likely in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors than in patients with HER2-negative tumors (P=.02). Age, Eastern Cooperative Oncology Group performance status, differentiation type, and clinical stage were not found to affect concordance. Among all patients, the survival time was significantly better in concordant patients than in nonconcordant patients (P<.001). Multivariate analysis revealed that concordance was an independent prognostic factor of overall survival in patients with gastric cancer (hazard ratio 0.312 [95% CI 0.187-0.521]). CONCLUSIONS: The treatment recommendations made by WFO and the MDT were mostly concordant in gastric cancer patients. If the WFO options are updated to include local treatment programs, the concordance will greatly improve. The HER2 status of patients with gastric cancer had a strong effect on the likelihood of concordance. Generally, survival was better in concordant patients than in nonconcordant patients.