Body mass index modified the effectiveness of low dose aspirin treatment on frozen-thawed embryo transfer outcome: a propensity score-matched study.

Background: Low-dose aspirin is one of the widely used adjuvants in assisted reproductive technologies with the hope of improving the live birth rate. However, the studies regarding its effects are conflicting. The study aimed to investigate the association between aspirin administration and live birth following frozen-thawed embryo transfer (FET) in patients with different body mass index (BMI). Methods: A retrospective cohort study was performed on 11,993 patients receiving FET treatments. 644 of which received a low-dose aspirin (100 mg/day) during endometrial preparation until 10 weeks after transfer. Propensity score matching was performed to avoid selection biases and potential confounders. Results: The clinical pregnancy rate and live birth rate were similar before matching (54.4% versus 55.4%, RR: 1.02, 95%CI: 0.95-1.09, and 46.3 versus 47.8, RR: 1.03, 95%CI: 0.95-1.12 respectively). A weak association in favor of aspirin administration was found in the matched cohort (49.5% versus 55.4%, RR: 1.12, 95%CI: 1.01-1.24, and 41.9% versus 47.8%, RR: 1.14, 95%CI: 1.01-1.29 respectively). However, when stratified the patients with WHO BMI criteria, a significant increase in live birth rate associated with aspirin treatment was found only in patients with low BMI (<18.5 kg/m2) in either unmatched (46.4% versus 59.8%, RR:1.29, 95%CI:1.07-1.55) or matched cohort (44% versus 59.8%, RR: 1.36, 95%CI: 1.01-1.83) but not in patients with higher BMI categories. With the interaction analysis, less association between aspirin and live birth appeared in patients with normal BMI (Ratio of OR:0.49, 95%CI: 0.29-0.81) and high BMI (Ratio of OR:0.57, 95%CI: 0.27-1.2) compared with patients with low BMI. Conclusion: BMI may be considered when evaluating aspirin's effect in FET cycles.

Efficacy of natural products in preventing oral mucositis resulting from cancer therapies: A network meta-analysis of randomized controlled trials.

BACKGROUND: Oral mucositis significantly compromises the quality of life for patients undergoing cancer therapies. This study aimed to evaluate the effectiveness of natural products in either preventing or alleviating oral mucositis resulting from cancer treatments. METHODS: A systematic review and network meta-analysis were conducted, sourcing data from the Cochrane Library, PubMed, Embase, Airiti Library, and Wan Fang Data Knowledge Service Platform until August 2023. The study was registered in PROSPERO (CRD42021285433). Confidence in Network Meta-Analysis (CINeMA) and R software 4.1.3 were used for analysis. RESULTS: From 1556 identified articles, 36 randomized controlled trials (RCTs) were analyzed, involving 2083 patients. Honey, notably, was found to significantly reduce the overall incidence of oral mucositis compared to standard care, with a relative risk (RR) of 0.80 (95% CI: 0.67-0.96). It was particularly effective against moderate-to-severe oral mucositis (grade ≥ 2), reducing incidence with RR of 0.48 (95% CI: 0.30-0.75) versus placebo and 0.56 (95% CI: 0.34-0.93) against standard care. Other natural products, including propolis, chamomile, and P. major L., also demonstrated significant efficacy in reducing the incidence of oral mucositis. Regarding pain relief, honey, and P. major L. emerged as effective, significantly reducing pain severity with a mean difference (MD) of -2.96 (95% CI: -3.80 to -1.94) compared to placebo. CONCUSSION: This network meta-analysis supports the use of honey, propolis, chamomile, and P. major L. as effective natural products in the prevention and treatment of oral mucositis among cancer patients. Specifically, honey is highlighted for its significant impact on reducing both the overall incidence and the severity of moderate-to-severe oral mucositis. By leveraging their anti-inflammatory and antioxidant properties, integrating these natural products into the standard care regimen could markedly improve the well-being of individuals undergoing cancer therapy.

An oncolytic HSV-1 armed with Visfatin enhances antitumor effects by remodeling tumor microenvironment against murine pancreatic cancer.

Oncolytic viruses (OVs) have shown potential in converting a "cold" tumor into a "hot" one and exhibit effectiveness in various cancer types. However, only a subset of patients respond to oncolytic virotherapy. It is important to understand the resistance mechanisms to OV treatment in pancreatic ductal adenocarcinoma (PDAC) to engineer oncolytic viruses. In this study, we used transcriptome RNA sequencing (RNA-seq) to identify Visfatin, which was highly expressed in the responsive tumors following OV treatment. To explore the antitumor efficacy, we modified OV-mVisfatin, which effectively inhibited tumor growth. For the first time, we revealed that Visfatin promoted the antitumor efficacy of OV by remodeling the tumor microenvironment, which involved enhancing CD8+ T cell and DC cell infiltration and activation, repolarizing macrophages towards the M1-like phenotype, and decreasing Treg cells using single-cell RNA sequencing (scRNA-seq) and flow cytometry. Furthermore, PD-1 blockade significantly enhanced OV-mVisfatin antitumor efficacy, offering a promising new therapeutic strategy for PDAC.

Serum AXL is a potential molecular marker for predicting COVID-19 progression.

Background: The severity, symptoms, and outcome of COVID-19 is thought to be closely linked to how the virus enters host cells. This process involves the key roles of angiotensin-converting enzyme 2 (ACE2) and the Tyrosine protein kinase receptor UFO (AXL) receptors. However, there is limited research on the circulating levels of ACE2 and AXL and their implications in COVID-19. Methods: A control group of 71 uninfected individuals was also included in the study. According to the Guidance for Corona Virus Disease 2019 (10th edition), a cohort of 358 COVID-19 patients were categorized into non-severe and severe cases. Serum ACE2/AXL levels in COVID-19 patients were detected by enzyme-linked immunosorbent assay (ELISA) at different time points post-COVID-19 infection, including days 0-7, 8-15, 31-179 and >180 days. Serum SARS-CoV-2 IgG/IgM antibodies in COVID-19 patients at the same intervals were assessed by using an iFlash 3000 Chemiluminescence Immunoassay Analyzer. The receiver operating characteristic (ROC) curves were used to assess the diagnostic value of the biological markers, and the association between laboratory parameters and illness progression were explored. Results: Compared with the uninfected group, the levels of ACE2 and AXL in the COVID-19 group were decreased, and the SARS-COV-2 IgG level was increased. AXL (AUC = 0.774) demonstrated a stronger predictive ability for COVID-19 than ACE2. In the first week after infection, only the level of AXL was statistically different between severe group and non-severe group. After first week, the levels of ACE2 and AXL were different in two groups. Moreover, in severe COVID-19 cases, the serum ACE2, AXL, and SARS-COV-2 IgM levels reached a peak during days 8-15 before declining, whereas serum SARS-COV-2 IgG levels continued to rise, reaching a peak at day 31-180 days before decreasing. In addition, the AXL level continued to decrease and the SARS-COV-2 IgG level continued to increase in the infected group after 180 days compared to the uninfected group. Conclusions: The levels of serum ACE2 and AXL correlate with COVID-19 severity. However, AXL can also provide early warning of clinical deterioration in the first week after infection. AXL appears to be a superior potential molecular marker for predicting COVID-19 progression.

Ultra-compact SOI-based higher-order mode pass wavelength demultiplexer.

We propose an ultra-compact mode filtering wavelength demultiplexer design with a footprint of 3µm×3µm. Our device can route input T E 1 mode signals at 1310 nm and 1550 nm to different output ports while simultaneously blocking fundamental transverse electric (T E 0) mode input. Our device is designed based on the topology optimization algorithm, which results in an ultra-compact footprint combining wavelength routing and mode filtering functions for the first time, to the best of our knowledge. Our final optimized devices demonstrated insertion losses of 1.26 dB and 1.47 dB for the C- and O-band output ports, respectively, with inter-port crosstalk as low as -21.25d B and -30.99d B. The extinction ratios between T E 1 mode and T E 0 mode are 24.02 dB and 30.12 dB at the 1310 nm and 1550 nm output ports. The combination of small footprint, broad transmission bandwidth, T E 1 to T E 0 mode selectively filtering, and C- and O-band T E 1 mode demultiplexing functions make this a uniquely versatile device that can play an important role in future high density mode-wavelength multiplexing systems.

Antibiotics-associated pseudomembranous colitis: a disproportionality analysis of the US food and drug administration adverse event reporting system (FAERS) database.

BACKGROUND: Evaluating antibiotics most commonly associated with pseudomembranous colitis (PMC) based on the real-world data is of great significance. RESEARCH DESIGN AND METHODS: We used the data from FAERS to evaluate the potential association between antibiotics and PMC by disproportionality analyzes. RESULTS: Eighty-one antibiotics which met the three algorithms simultaneously were enrolled. There were 1683 reports of PMC associated with the enrolled antibiotics. In the top 24 antibiotics, cefoxitin, streptomycin, fosfomycin, and micafungin had a high risk of PMC, but there were few reports in the literature. CONCLUSIONS: This study was of great significance for healthcare professionals to realize the potential PMC risks of antibiotics.

Effects of different types of Ringer's solution on patients with traumatic haemorrhagic shock: a prospective cohort study.

OBJECTIVE: To compare the fluid resuscitation effect of sodium acetate Ringer's solution and sodium bicarbonate Ringer's solution on patients with traumatic haemorrhagic shock. METHOD: We conducted a prospective cohort study in our emergency department on a total of 71 patients with traumatic haemorrhagic shock admitted between 1 December 2020 and 28 February 2022. Based on the time of admission, patients were randomly divided into a sodium bicarbonate Ringer's solution group and sodium acetate Ringer's solution group, and a limited rehydration resuscitation strategy was adopted in both groups. General data were collected separately, and the patients' vital signs (body temperature, respiration, blood pressure and mean arterial pressure (MAP)), blood gas indices (pH, calculated bicarbonate (cHCO3-), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (pCO2) and clearance of lactate (CLac)), shock indices, peripheral platelet counts, prothrombin times and plasma fibrinogen levels were measured and compared before and 1 h after resuscitation. RESULTS: The post-resuscitation heart rate of the sodium bicarbonate Ringer's solution group was significantly lower than that of the sodium acetate Ringer's solution group (p < 0.05), and the MAP was also significantly lower (p < 0.05). The patients in the sodium bicarbonate Ringer's solution group had significantly higher pH, cHCO3- and PaO2 values and lower pCO2 and CLac values (p < 0.05) than those in the sodium acetate Ringer's solution group, and the post-resuscitation peripheral platelet counts and fibrinogen levels were significantly higher, with shorter plasma prothrombin times and smaller shock indices (p < 0.001). CONCLUSION: Sodium bicarbonate Ringer's solution is beneficial for maintaining MAP at a low level after resuscitation. The use of sodium bicarbonate Ringer's solution in limited fluid resuscitation has positive results and is of high clinical value.

Evaluating cardiac disorders associated with triazole antifungal agents based on the US Food and Drug Administration Adverse Event reporting system database.

Introduction: Triazole antifungal agents are widely used to treat and prevent systemic mycoses. With wide clinical use, the number of reported adverse events has gradually increased. The aim of this study was to analyze the cardiac disorders associated with TAAs (fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole) based on data from the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System. Methods: Data were extracted from the FAERS database between the first quarter of 2004 and third quarter of 2022. The clinical characteristics in TAA-associated cardiac AE reports were analyzed. Disproportionality analysis was performed to evaluate the potential association between AEs and TAAs using the reporting odds ratio (ROR) and proportional reporting ratio (PRR). Results: Among 10,178,522 AE reports, 1719 reports were TAA-associated cardiac AEs as primary suspect drug. Most reports were related to fluconazole (38.34%), voriconazole (28.56%) and itraconazole (26.76%). Itraconazole (N = 195, 42.39%) and isavuconazole (N = 2, 14.29%) had fewer serious outcome events than three other drugs including fluconazole, voriconazole, and posaconazole. 13, 11, 26, 5 and 1 signals were detected for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively. The number of new signals unrecorded in the drug label was 9, 2, 13, 2 and 0 for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively. Conclusion: Isavuconazole might be the safest of the five TAAs for cardiac AEs. TAA-associated cardiac disorders may result in serious adverse outcomes. Therefore, in addition to AEs on the drug label, we should pay attention to new AEs unrecorded on the drug label during the clinical use of TAAs.

Cancer testis antigen MAGEA3 in serum and serum-derived exosomes serves as a promising biomarker in lung adenocarcinoma.

Cancer testis antigen (CTA) Melanoma Antigen Gene A3 (MAGEA3) were overexpressed in multiple tumor types, but the expression pattern of MAGEA3 in the serum of lung adenocarcinoma (LUAD) remains unclear. Clinically derived serum and serum exosome samples were used to assess the mRNA expression of MAGEA3 and MAGEA4 by qRT-PCR, and serum MAGEA3 and MAGEA4 protein expression were evaluated by ELISA in total 133 healthy volunteers' and 289 LUAD patients' serum samples. An analysis of the relationship of the mRNA and protein expression of MAGEA3 and MAGEA4 with clinicopathologic parameters was performed and the diagnostic value of MAGEA3 and MAGEA4 was plotted on an ROC curve. In addition, the correlation of MAGEA3 mRNA with infiltrating immune cells was investigated through TIMER, the CIBERSORT algorithm and the TISIDB database. Expression of serum and serum exosome MAGEA3 and MAGEA4 mRNA were significantly higher in LUAD patients than in healthy donors. MAGEA3 mRNA associated with tumor diameter, TMN stage, and NSE in LUAD serum samples, and MAGEA3 mRNA correlated with N stage in serum-derived exosomes, possessing areas under the curve (AUC) of 0.721 and 0.832, respectively. Besides, serum MAGEA3 protein levels were elevated in LUAD patients, and were closely related to stage and NSE levels, possessing AUC of 0.781. Further analysis signified that the expression of MAGEA3 mRNA was positive correlation with neutrophil, macrophages M2, dendritic cells resting, and eosinophilic, but negatively correlated with B cells, plasma cells, CD8 + T cells, CD4 + T cells, Th17 cells, macrophages and dendritic cells. Collectively, our results suggested that the MAGEA3 expression in mRNA and protein were upregulated in LUAD, and MAGEA3 could be used as a diagnostic biomarker and immunotherapy target for LUAD patients.

Electrospinning Chitosan/Fe-Mn Nanofibrous Composite for Efficient and Rapid Removal of Arsenite from Water.

Efficient removal of extremely mobile and toxic As(III) from water is a challenging but critical task. Herein, we developed a functionalized sorbent of chitosan nanofiber with iron-manganese (Fe-Mn@CS NF) using a one-step hybrid electrospinning approach to remove trace As(III) from water. Batch adsorption studies were performed to determine the adsorption efficiency under a variety of conditions, including contact time, starting concentration of As(III), ionic strength, and the presence of competing anions. The experimental results demonstrated that the concentration of As(III) dropped from 550 to less than 1.2 µg/L when using 0.5 g/L Fe-Mn@CS NF. This demonstrates the exceptional adsorption efficiency (99.8%) of Fe-Mn@CS NF for removing As(III) at pH 6.5. The kinetic tests revealed that the adsorption equilibrium was reached in 2.6 h, indicating a quick uptake of As(III). The ionic strength effect analysis showed that the adsorbed As(III) formed inner-sphere surface complexes with Fe-Mn@CS NF. The presence of SO42- or F- had a negligible impact on As(III) uptake, while the presence of PO43- impeded As(III) absorption by competing for adsorption sites. The exhausted sorbent could be effectively regenerated with a dilute NaOH solution. Even after 10 cycles of regenerating Fe-Mn@CS NF, the adsorption efficiency of As(III) in natural groundwater was maintained over 65%. XPS and FTIR analyses show that the presence of M-OH and C-O groups on the sorbent surface is essential for removing As(III) from water. Overall, our study highlights the significant potential of Fe-Mn@CS NF for the efficient and quick elimination of As(III) from water.

Oral aspirin for preventing colorectal adenoma recurrence: A systematic review and network meta-analysis of randomized controlled trials.

Colorectal adenomas have the potential of malignant transformation if left untreated. Multiple randomized controlled trials have been performed to evaluate the efficacy of aspirin in preventing colorectal adenoma recurrence in a population with a history of colorectal adenoma but not colorectal cancer, however, the relationship between aspirin dose and colorectal adenoma recurrence remains unclear. We conducted pairwise meta-analysis, meta-regression, trial sequential analysis, and network meta-analysis of all eligible studies. The ROB 2.0 tool was used to assess the risk of bias in the studies. The confidence in network meta-analysis (CINeMA) approach was used to evaluate the confidence of the network meta-analysis results. The network meta-analysis included eight RCTs (nine reports), comprising four on aspirin (low or high dose) alone and four on aspirin combined with another medication, all compared with placebo. In the network meta-analysis, low-dose aspirin (LDA <300 mg per day) was more effective than high-dose aspirin (HDA ≥300 mg per day) and placebo, with risk ratios of 0.76 (95% CI: 0.58 to 0.99) and 0.7 (95% CI: 0.54 to 0.91), respectively. LDA was the optimal treatment relative to HDA and placebo (P-score = 0.99). In the trial sequential analysis, LDA was only more effective than placebo when the number of included participants exceeded the optimal information size; this was not the case for HDA. LDA has statistically significant efficacy for colorectal adenoma prevention, but compared with HDA, its efficacy remains uncertain. Further trials are therefore required.

Recent Progress in Nucleic Acid Pulmonary Delivery toward Overcoming Physiological Barriers and Improving Transfection Efficiency.

Pulmonary delivery of therapeutic agents has been considered the desirable administration route for local lung disease treatment. As the latest generation of therapeutic agents, nucleic acid has been gradually developed as gene therapy for local diseases such as asthma, chronic obstructive pulmonary diseases, and lung fibrosis. The features of nucleic acid, specific physiological structure, and pathophysiological barriers of the respiratory tract have strongly affected the delivery efficiency and pulmonary bioavailability of nucleic acid, directly related to the treatment outcomes. The development of pharmaceutics and material science provides the potential for highly effective pulmonary medicine delivery. In this review, the key factors and barriers are first introduced that affect the pulmonary delivery and bioavailability of nucleic acids. The advanced inhaled materials for nucleic acid delivery are further summarized. The recent progress of platform designs for improving the pulmonary delivery efficiency of nucleic acids and their therapeutic outcomes have been systematically analyzed, with the application and the perspectives of advanced vectors for pulmonary gene delivery.

Comparative analysis of preoperative chemoradiotherapy and upfront surgery in the treatment of upper-half rectal cancer: oncological benefits, surgical outcomes, and cost implications.

The value of neoadjuvant chemoradiotherapy (CRT) is not absolutely clear for upper-half (> 7-15 cm) rectal cancer. This study aimed to compare the efficacy and safety of radical surgery with preoperative CRT vs. upfront surgery (US) in Chinese patients with stage II and III upper-half rectal cancer. A total of 809 patients with locally advanced upper-half rectal cancer between 2017 and 2021 were enrolled retrospectively (280 treated with CRT and 529 treated with US). Through 1:1 propensity score matching, the CRT (172 patients) and US (172 patients) groups were compared for short-term postoperative results and long-term oncological and functional outcomes. In the entire cohort, patients in the CRT group had a younger age, lower distance from the anal verge (DAV), and higher rates of cT4 stage, cN2 stage, mrCRM positivity, EMVI positivity, CEA elevation, and CA-199 elevation than those in the US group. The 5-year disease-free survival (DFS) was lower in the CRT group than in the US group (76% vs. 84%, p = 0.022), while the 5-year overall survival (OS) was comparable between the two groups (85% and 88%, p = 0.084). The distant metastasis rate was higher in the CRT group than in the US group (12.5% vs. 7.8%, p = 0.028), though the local recurrence rate was similar between the two groups (1.1% and 1.3%, p = 1.000). After performing PSM, the 5-year OS (86% vs. 88% p = 0.312), the 5-year DFS (79% vs. 80%, p = 0.435), the local recurrence rate (1.2% vs. 1.7%, p = 1.000), and the distant metastasis rate (11.0% vs. 9.3%, p = 0.593) were comparable between the two groups. Notable pathological downstaging was observed in the CRT group, with a pathological complete response (PCR) rate of 14.5%. In addition, patients in the CRT group had a lower proportion of pT3 (61.6% vs. 77.9%, p < 0.001), pN + (pN1, 15.1% vs. 30.2%, pN2, 9.3% vs. 20.3%, p < 0.001), stage III (24.4% vs. 50.6%, p < 0.001), perineural invasion (19.8% vs. 32.0%, p = 0.014), and lymphovascular invasion (9.3% vs. 25.6%, p < 0.001) than those in the US group. Postoperative complications and long-term functional results were similar, yet there was a trend toward a higher conversion to laparotomy rate (5 (2.9%) vs. 0 (0.0%), p = 0.061) and higher rates of robotic surgery (11.6% vs. 4.7%, p < 0.001), open surgery (7.0% vs. 0.6%, p < 0.001), diverting stoma (47.1% vs. 25.6%, p < 0.001), and surgery costs (1473.6 ± 106.5 vs. 1140.3 ± 54.3$, p = 0.006) in the CRT group. In addition, EMVI (OR = 2.516, p = 0.001) was the only independent risk factor associated with poor response to CRT, and in subgroup analysis of EMVI + , CRT group patients presented a lower 5-year DFS (72.9% vs. 80.5%, p = 0.025) compared to US group patients. CRT prior to surgery has no additional oncological benefits over US in the treatment of upper-half rectal cancer. In contrast, CRT is associated with increased rates of conversion to laparotomy, stoma creation and higher surgery costs. Surgeons tend to favor robotic surgery in the treatment of complex cases such as radiated upper-half rectal cancers. Notably, EMVI + patients with upper-half rectal cancer should be encouraged to undergo upfront surgery, as preoperative CRT may not provide benefits and may lead to delayed treatment effects.

Hypofractionated radiotherapy for refractory or relapsed aggressive B-cell lymphoma in the rituximab era.

BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.

MRI-based parameters and clinical risk factors to predict lymph node metastasis in patients with ypT0 rectal cancer after neoadjuvant chemoradiotherapy.

BACKGROUNDS: The aim of this study was to assess the significant risk factors that predict lymph node metastasis in ypT0 patients with locally advanced rectal cancer following chemoradiotherapy (CRT). Additionally, the study aimed to identify high-risk groups who would not be suitable candidates for a rectal-preserving strategy, despite achieving a complete tumour response. METHODS: Between 2013 and 2021, 226 ypT0 patients with stages II/III rectal cancer underwent CRT and radical surgery were enrolled. Two groups of patients were evaluated: those with lymph nodes metastasis and those without. The selection of variables for multivariable logistic regression was conducted through bivariate logistic regression analysis. Furthermore, the determination of optimal cutoff values for risk factors was achieved using ROC curve analysis. RESULTS: Nearly 8% (18/226) of patients with ypT0 had positive lymph nodes (LN) on final pathology. Four variables resulted as being independent factors of LN metastasis: pre-CRT tumour movability (OR = 8.618, P = 0.003), pre-CRT maximal LN size (OR = 28.474, P = 0.004), post-CRT tumour vertical length (OR = 1.492, P = 0.050), post-CRT anaemia (OR = 10.288, P = 0.001). The optimal cutoff point of pre-CRT maximal LN size and post-CRT tumour vertical length was 7.50 mm and 3.05 cm, respectively. CONCLUSION: The prevalence of lymph node metastasis remains at 8% among patients who achieve pathological complete regression of the primary tumour. In instances where patients are considered appropriate candidates for a rectal-preserving strategy after clinical complete remission, careful consideration should be given to the selection of this strategy if specific risk factors are present. These risk factors encompass a maximal LN size surpassing 7.50 mm prior to CRT, a fixed tumour prior to CRT, a tumour vertical length exceeding 3.05 cm after CRT, and the existence of anaemia subsequent to CRT.

The immune inflammation factors associated with disease severity and poor prognosis in patients with COVID-19: A retrospective cohort study.

Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. It is essential to explore the immune response characteristics of peripheral circulation in COVID-19 patients to reveal pathogenesis and predict disease progression. In this study, the levels of total immunoglobulins (IgG, IgM, IgA), complement (C3, C4)，lymphocyte subsets (CD3+ cell，CD4+ cell，CD8+ cell, NK cell, CD19+ cell and CD45+ cell) and cytokines (IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IL-12p, IL-1ß, TNF-α, IFN-α and IFN-γ) were retrospectively analyzed in COVID-19 patients. A total of 513 patients were enrolled in this study, cases were distributed according to clinical status as mild or moderate (n = 212), severe survivors (n = 197) and severe non-survivors (n = 104). IL-6, IL-8, IL-10 and IFN-γ were increased in severe patients compared with non-severe patients, despite decreased CD45+ cell, CD3+ cell, CD4+ cell, CD8+ cell, CD19+ cell, and NK cell. Compared with severe survivors, the levels of L-6, IL-8 and IL-10 in non-survivors increased significantly, and levels of C3, CD45+ cell, CD3+ cell，CD4+ cell，CD8+ cell, and NK cell decreased. Moreover, age, IL-8, IL-10, CD8+cells and NK cell were independent risk factors for the severity of COVID-19. Multivariable regression showed increasing odds ratio of in-hospital death associated with tumor, older age, higher IL-8 level, and decreasing odds ratio of in-hospital death associated with increased levels of CD8+cell and NK cell. Finally, patients with tumor, or high IL-6 or high IL-10 expression and lower CD8+ or lower NK levels exhibited a significantly shorter survival time. In conclusion, our study provides findings of the immunological characteristics associated with disease severity to predict the progression of COVID-19. The immune inflammation factors, such as IL-6, IL-8, IL-10, CD8+ cell and NK cell, could serve as excellent biomarkers for monitoring or predicting COVID-19 progression therapeutic to COVID-19 patients.

Collagen-Targeting Self-Assembled Nanoprobes for Multimodal Molecular Imaging and Quantification of Myocardial Fibrosis in a Rat Model of Myocardial Infarction.

Currently, inadequate early diagnostic methods hinder the prompt treatment of patients with heart failure and myocardial fibrosis. Magnetic resonance imaging is the gold standard noninvasive diagnostic method; however, its effectiveness is constrained by low resolution and challenges posed by certain patients who cannot undergo the procedure. Although enhanced computed tomography (CT) offers high resolution, challenges arise owing to the unclear differentiation between fibrotic and normal myocardial tissue. Furthermore, although echocardiography is real-time and convenient, it lacks the necessary resolution for detecting fibrotic myocardium, thus limiting its value in fibrosis detection. Inspired by the postinfarction accumulation of collagen types I and III, we developed a collagen-targeted multimodal imaging nanoplatform, CNA35-GP@NPs, comprising lipid nanoparticles (NPs), encapsulating gold nanorods (GNRs) and perfluoropentane (PFP). This platform facilitated ultrasound/photoacoustic/CT imaging of postinfarction cardiac fibrosis in a rat model of myocardial infarction (MI). The surface-modified peptide CNA35 exhibited excellent collagen fiber targeting. The strong near-infrared light absorption and substantial X-ray attenuation of the nanoplatform rendered it suitable for photoacoustic and CT imaging. In the rat model of MI, our study demonstrated that CNA35-GNR/PFP@NPs (CNA35-GP@NPs) achieved photoacoustic, ultrasound, and enhanced CT imaging of the fibrotic myocardium. Notably, the photoacoustic signal intensity positively correlated with the severity of myocardial fibrosis. Thus, this study presents a promising approach for accurately detecting and treating the fibrotic myocardium.

Major adverse cardiovascular events of vascular endothelial growth factor tyrosine kinase inhibitors among patients with different malignancy: A systemic review and network meta-analysis.

BACKGROUND: Vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) are a common cancer treatment. However, the pharmacologic characteristics of VEGF-TKIs may influence cardiovascular risks. The relative risks of major adverse cardiovascular events (MACEs) associated with VEGF-TKIs are poorly understood. METHODS: We searched PubMed, Embase, and ClinicalTrials.gov from inception until August 31, 2021, for phase II/III randomized controlled trials of 11 VEGF-TKIs (axitinib, cabozantinib, lenvatinib, pazopanib, ponatinib, ripretinib, regorafenib, sorafenib, sunitinib, tivozanib, and vandetanib). The endpoints were heart failure, thromboembolism, and cardiovascular death. The Mantel-Haenszel method was used to calculate the risk of VEGF-TKI among users by comparing it to nonusers. Pairwise meta-analyses with a random-effects model were used to estimate the risks of the various VEGF-TKIs. We estimated ranked probability with a P-score and assessed credibility using the Confidence in Network Meta-Analysis framework. RESULTS: We identified 69 trials involving 30 180 patients with cancer. The highest risk of MACEs was associated with high-potency tivazonib (odds ratio [OR]: 3.34), lenvatinib (OR: 3.26), and axitinib (OR: 2.04), followed by low-potency pazopanib (OR: 1.79), sorafenib (OR: 1.77), and sunitinib (OR: 1.66). The risk of heart failure significantly increased in association with less-selective sorafenib (OR: 3.53), pazopanib (OR: 3.10), and sunitinib (OR: 2.65). The risk of thromboembolism significantly increased in association with nonselective lenvatinib (OR: 3.12), sorafenib (OR: 1.54), and sunitinib (OR: 1.53). Higher potency (tivozanib, axitinib) and lower selectivity (sorafenib, vandetanib, pazopanib, sunitinib) were associated with a higher probability of heart failure. Low selectivity (lenvatinib, cabozantinib, sorafenib, sunitinib) was associated with a higher probability of thromboembolism. CONCLUSION: Higher-potency and lower-selectivity VEGF-TKIs may influence the risks of MACEs, heart failure, and thromboembolism. These findings may facilitate evidence-based decision-making in clinical practice.

Frailty and Other Factors Associated With Early Outcomes in Middle-to Older Age Trauma Patients: A Prospective Cohort Study.

OBJECTIVES: To prospectively investigate associations of frailty and other predictor variables with functional recovery and health outcomes in middle-aged and older patients with trauma. DESIGN: Single-center prospective cohort study. SETTING: Emergency department of Wan Fang Hospital in Taiwan. PARTICIPANTS: Trauma patients aged 45 and older. MEASUREMENTS: Frailty was assessed with the Clinical Frailty Scale (CFS). Injury mechanisms, pre-existing diseases, and fracture locations were recorded at baseline. The primary outcome was functional recovery assessed using the Barthel Index (BI). Secondary outcomes were new care needs, unscheduled return visits, and falls 3 months postinjury. RESULTS: A total of 588 participants were included in the final analysis. For every one-point increase in the CFS, the multivariable-adjusted odds ratio (OR, 95% confidence interval [CI]) of failure to retain the preinjury BI was 1.34 (1.16-1.55); associations were consistent across levels of age and injury severities. Significant joint associations of frailty and age with poor functional recovery were observed. CFS was also associated with new care needs (OR for every one-point increase, 1.36, 95% CI, 1.17-1.58), unscheduled return visits (OR 1.26, 95% CI, 1.04-1.51), and falls (OR 1.23, 95% CI, 1.01-1.51). Other variables associated with failure to retain preinjury BI included road traffic accident and presence of hip fracture. CONCLUSION: Frailty was significantly associated with poor functional and health outcomes regardless of injury severity in middle-aged and older patients with trauma. Injury mechanisms and fracture locations were also significant predictors of functional recovery postinjury.

Assessment of Prophylactic Internal Carotid Artery Management in Postradiation Nasopharyngeal Necrosis Patients.

OBJECTIVE: Postradiation nasopharyngeal necrosis (PRNN) frequently develops after second-course radiotherapy for nasopharyngeal carcinoma (NPC). PRNN can lead to internal carotid artery (ICA) massive hemorrhage due to ICA rupture, resulting in sudden death. This study aims to explore the pretreatment of the ICA to prevent fatal massive hemorrhage in PRNN patients. STUDY DESIGN: Retrospective cohort study. SETTING: Sun Yat-sen University Cancer Center. METHODS: Patients diagnosed with NPC and PRNN from January 2010 to September 2022 were included. The Cox proportional hazards regression analysis was performed to analyze risk factors for massive hemorrhage and survival. A nomogram was developed to integrate prognostic models and perform parameter calibration. RESULTS: Two hundred and fifty-four PRNN patients were included in this study. Prophylactic ICA occlusion significantly reduced the risk of ICA hemorrhage compared to no prophylactic ICA occlusion (3.6% vs 40.6%, P < .001). Surgical repair on necrosis significantly prevented hemorrhage and improved survival. The nomogram, incorporating the above 2 factors and the nearest distance from necrosis to ICA ≤ 3 mm, exhibited excellent discriminative ability for hemorrhage. We identified 3 high-risk factors that indicate the need for prophylactic ICA management in PRNN patients: (1) exposure of ICA by rhinoscopy; (2) signs of ICA erosion on MRA scanning; (3) the depth of soft tissue coverage surrounding the ICA wall within the necrotic cavity is less than 3 mm on magnetic resonance imaging. CONCLUSION: We have identified 3 high-risk factors for PRNN patients that necessitate prophylactic ICA management. These findings are expected to contribute to improving the quality of life and overall survival of PRNN patients.