Textbook outcome in low rectal cancer after neoadjuvant chemoradiotherapy: Post hoc analysis of the LASRE randomized clinical trial.

BACKGROUND: Textbook outcome has been incorporated into quality assessment measures in various oncological settings; however, it has not been applied to patients with low rectal cancer after neoadjuvant chemoradiotherapy (nCRT). This study aimed to examine the prevalence and predictors of achieving a textbook outcome in patients undergoing surgical resection of low rectal cancer after nCRT. PATIENTS AND METHODS: This study was a post hoc subgroup analysis of the prospective multicentric LASRE trial, which specifically enrolled patients with rectal cancer located within 5 cm from the dentate line at diagnosis, tumors with diameters less than 6 cm, and patients who underwent radical laparoscopic or open resection. A total of 597 patients who had clinically staged cT3-4aN0-2M0 tumors with diameters less than 6 cm and who underwent neoadjuvant chemoradiotherapy followed by radical resection were included. RESULTS: Textbook outcome was achieved in 60.0 % of patients. Multivariate logistic regression analysis revealed that body mass index >25 kg/m2 (OR = 0.594, P = 0.01), tumor distance from the anal verge >40 mm (OR = 5.518, P < 0.001), operative time >202 min (OR = 0.675, P = 0.04), and laparoscopic approach (OR = 1.497, P = 0.04) were independently predictive factors for the achievement of a textbook outcome in low rectal cancer patients undergoing nCRT and radical resection. A predictive nomogram for achieving a textbook outcome was constructed, yielding a C-index of 0.727. CONCLUSIONS: Laparoscopic resection exhibited promising potential in improving the probability of achieving a textbook outcome.

Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice.

OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.

Safety and efficacy of indocyanine green fluorescence imaging-guided laparoscopic para-aortic lymphadenectomy for left-sided colorectal cancer:A preliminary case-matched study.

AIM: This study is aimed to explore the safety and feasibility of indocyanine green (ICG) fluorescence imaging guidance in laparoscopic para-aortic lymph node (PALN) dissection for left-sided colorectal cancer (CRC) patients with clinically suspected PALN metastasis. METHOD: A total of 151 patients who underwent primary tumor resection and laparoscopic PALN dissection for left-sided CRC were included, with 20 patients in the ICG group and 131 patients in the non-ICG group. The surgical outcomes, postoperative complications, and pathological results, such as the number of harvested and metastatic lymph nodes were compared between groups after propensity score matching. RESULTS: Following propensity score matching, the ICG group had 20 patients, and the non-ICG group had 53 patients, and the two groups were similar in baseline characteristics. No significant differences were observed in overall intraoperative and postoperative complications between groups, except for chylous leakage, where the ICG group had a longer time to a normal diet. The number of harvested pericolic/perirectal and intermediate lymph nodes were comparable between the two groups, while the ICG group had a significantly higher number of total harvested lymph nodes (39 [14-78] vs. 29 [11-70], P = 0.001), inferior mesenteric artery lymph nodes (IMALN, 6 [0-17] vs. 3 [0-11], P = 0.006), and PALNs (9 [3-29] vs. 5 [1-37], P = 0.001). CONCLUSION: ICG fluorescence imaging could increase the retrieval of IMALN, PALN, and total lymph nodes, and potentially improve the completeness of laparoscopic PALN dissection in patients with left-sided CRC.

Accurate preoperative prediction of nodal metastasis in papillary thyroid microcarcinoma: Towards optimal management of patients.

OBJECTIVE: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies. METHODS: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. RESULTS: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. CONCLUSION: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.

The role of personal, relational, and collective self-esteem in predicting acute salivary cortisol response and perceived stress.

Personal self-esteem (PSE) has been well recognized as a buffer against stress; however, the effects of other types of self-esteem, such as relational self-esteem (RSE) and collective self-esteem (CSE), on stress have not been adequately explored. This study investigated the roles of PSE, RSE, and CSE in reducing stress response. The Rosenberg, Relational, and Collective Self-Esteem Scales were adopted to assess PSE, RSE, and CSE, respectively. Participants underwent an acute social stress paradigm, and their acute stress response was assessed using subjective stress reports and salivary cortisol levels. Chronic stress level was estimated using the Perceived Stress Scale and hair cortisol concentration. The results showed that PSE was negatively correlated with salivary cortisol response during acute social stress; however, no significant associations were found between any type of self-esteem and subjective stress reports. For chronic stress, all types of self-esteem were negatively associated with perceived stress level, but not with hair cortisol concentration. Further hierarchical regression analyses suggested that only PSE negatively predicted acute salivary cortisol response and perceived stress level. Overall, the findings suggest the essential role of PSE in predicting acute salivary cortisol responses and perceived stress.

An Antidehydration Hydrogel Based on Zwitterionic Oligomers for Bioelectronic Interfacing.

Hydrogels are ideal interfacing materials for on-skin healthcare devices, yet their susceptibility to dehydration hinders their practical use. While incorporating hygroscopic metal salts can prevent dehydration and maintain ionic conductivity, concerns arise regarding metal toxicity due to the passage of small ions through the skin barrier. Herein, an antidehydration hydrogel enabled by the incorporation of zwitterionic oligomers into its network is reported. This hydrogel exhibits exceptional water retention properties, maintaining ≈88% of its weight at 40% relative humidity, 25 °C for 50 days and about 84% after being heated at 50 °C for 3 h. Crucially, the molecular weight design of the embedded oligomers prevents their penetration into the epidermis, as evidenced by experimental and molecular simulation results. The hydrogel allows stable signal acquisition in electrophysiological monitoring of humans and plants under low-humidity conditions. This research provides a promising strategy for the development of epidermis-safe and biocompatible antidehydration hydrogel interfaces for on-skin devices.

Application of spectroscopic techniques combined with chemometrics to the authenticity and quality attributes of rice.

Rice is a staple food for two-thirds of the world's population and is grown in over a hundred countries around the world. Due to its large scale, it is vulnerable to adulteration. In addition, the quality attribute of rice is an important factor affecting the circulation and price, which is also paid more and more attention. The combination of spectroscopy and chemometrics enables rapid detection of authenticity and quality attributes in rice. This article described the application of seven spectroscopic techniques combined with chemometrics to the rice industry. For a long time, near-infrared spectroscopy and linear chemometric methods (e.g., PLSR and PLS-DA) have been widely used in the rice industry. Although some studies have achieved good accuracy, with models in many studies having greater than 90% accuracy. However, higher accuracy and stability were more likely to be obtained using multiple spectroscopic techniques, nonlinear chemometric methods, and key wavelength selection algorithms. Future research should develop larger rice databases to include more rice varieties and larger amounts of rice depending on the type of rice, and then combine various spectroscopic techniques, nonlinear chemometric methods, and key wavelength selection algorithms. This article provided a reference for a more efficient and accurate determination of rice quality and authenticity.

The landscape of innate and adaptive immune cell subsets in patients with adult-onset Still's disease.

OBJECTIVE: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder. The understanding of the changes in adaptive immune cells and the crosstalk between innate and adaptive immune systems in AOSD is limited. This study aimed to examine the peripheral immune cell composition and inflammatory protein levels in AOSD patients. METHODS: Twenty-nine active AOSD patients were enrolled. Flow cytometry was used to analyze the cell populations in peripheral blood. Antibody chips were utilized to detect the protein expression profile in serum. RESULTS: In active AOSD patients, there was an increase in the percentage of classical and non-classical monocytes among peripheral blood mononuclear cells. The proportion of natural killer (NK) cells decreased, with an increase in CD56dim NK1 cells and a decrease in CD56bright NK2 cells compared with healthy controls (HC). The percentage of naïve central memory T cells was decreased, while the percentage of effector and effector memory T cells was increased among adaptive lymphocytes. The proportion of naïve B and memory B cells was decreased, while plasma cells were increased in AOSD patients, indicating activation of the adaptive immune system. Additionally, the serum levels of 40 proteins were elevated in AOSD patients, primarily involved in cytokine-cytokine receptor interaction, inflammatory response, and regulation of MAPK cascade. CONCLUSION: Our findings showed the activation of the innate and adaptive immune system in AOSD. The protein-protein interaction analysis suggested potential communication between innate and adaptive cell subsets. These findings provide new insights into the pathogenesis of the disease and the development of targeted therapies.

Risk factors in antiphospholipid antibody-associated valvular heart disease: A 383-patient cohort study.

Valvular heart disease (VHD) is a prevalent cardiac manifestation in antiphospholipid syndrome (APS) patients. However, risk factors and predictors for antiphospholipid antibody-associated VHD (aPL-VHD) remain vague. We aimed to assess the risk of developing aPL-VHD in aPL-positive patients, by establishing a clinical prediction model upon a cross-sectional cohort from APS-Shanghai database, including 383 APS patients and durable aPL carriers with transthoracic echocardiography investigation. The prevalence of aPL-VHD was 11.5%. Multivariate logistic regression analysis identified three independent risk factors for aPL-VHD: anti-ß2GPI IgG (OR 5.970, P < 0.001), arterial thrombosis (OR 2.758, P = 0.007), and stratified estimated glomerular filtration rate levels (OR 0.534, P = 0.001). A prediction model for aPL-VHD, incorporating the three factors, was further developed, which demonstrated good discrimination with a C-index of 0.855 and 0.841 (after bootstrapping), and excellent calibration (P = 0.790). We provide a practical tool for assessing the risk of developing VHD among aPL-positive patients.

CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis.

Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19.

Activation of Platelet mTORC2/Akt Pathway by Anti-ß2GP1 Antibody Promotes Thrombosis in Antiphospholipid Syndrome.

BACKGROUND: Anti-ß2GP1 (ß2-glycoprotein 1) antibodies are the primary pathogenic antibody to promote thrombosis in antiphospholipid syndrome (APS), yet the underlying mechanism remains obscure. We aimed to explore the intracellular pathway that mediated platelet activation. METHODS: Platelets were isolated from patients with APS and subjected to RNA sequencing. Platelet aggregation, the release of platelet granules, platelet spreading, and clot retraction were detected to evaluate platelet activation. We purified anti-ß2GP1 antibodies from patients with APS and the total IgG from healthy donors to stimulate platelets with/without FcγRIIA (Fcγ receptor IIA) blocking antibody or Akt (protein kinase B) inhibitor. Platelet-specific Sin1 (stress-activated protein kinase-interacting protein) deficiency mice were established. The thrombus model of inferior vena cava flow restriction, ferric chloride-induced carotid injury model, and laser-induced vessel wall injury in cremaster arterioles model were constructed after administration of anti-ß2GP1 antibodies. RESULTS: Combined RNA sequencing and bioinformatics analysis suggested that APS platelets exhibited increased levels of mRNA associated with platelet activation, which was in line with the hyperactivation of APS platelets in response to stimuli. Platelet activation in APS platelets was accompanied by upregulation of the mTORC2 (mammalian target of the rapamycin complex 2)/Akt pathway and increased levels of SIN1 phosphorylation at threonine 86. Anti-ß2GP1 antibody derived from patients with APS enhanced platelet activation and upregulated the mTORC2/Akt pathway. Moreover, the Akt inhibitor weakened the potentiating effect of the anti-ß2GP1 antibody on platelet activation. Notably, Sin1 deficiency suppresses anti-ß2GP1 antibody-enhanced platelet activation in vitro and thrombosis in all 3 models. CONCLUSIONS: This study elucidated the novel mechanism involving the mTORC2/Akt pathway, which mediates the promotion of platelet activation and induction of thrombosis by the anti-ß2GP1 antibody. The findings suggest that SIN1 may be a promising therapeutic target for the treatment of APS.

Neural habituation during acute stress signals a blunted endocrine response and poor resilience.

BACKGROUND: A blunted hypothalamic-pituitary-adrenal (HPA) axis response to acute stress is associated with psychiatric symptoms. Although the prefrontal cortex and limbic areas are important regulators of the HPA axis, whether the neural habituation of these regions during stress signals both blunted HPA axis responses and psychiatric symptoms remains unclear. In this study, neural habituation during acute stress and its associations with the stress cortisol response, resilience, and depression were evaluated. METHODS: Seventy-seven participants (17-22 years old, 37 women) were recruited for a ScanSTRESS brain imaging study, and the activation changes between the first and last stress blocks were used as the neural habituation index. Meanwhile, participants' salivary cortisol during test was collected. Individual-level resilience and depression were measured using questionnaires. Correlation and moderation analyses were conducted to investigate the association between neural habituation and endocrine data and mental symptoms. Validated analyses were conducted using a Montreal Image Stress Test dataset in another independent sample (48 participants; 17-22 years old, 24 women). RESULTS: Neural habituation of the prefrontal cortex and limbic area was negatively correlated with cortisol responses in both datasets. In the ScanSTRESS paradigm, neural habituation was both positively correlated with depression and negatively correlated with resilience. Moreover, resilience moderated the relationship between neural habituation in the ventromedial prefrontal cortex and cortisol response. CONCLUSIONS: This study suggested that neural habituation of the prefrontal cortex and limbic area could reflect motivation dysregulation during repeated failures and negative feedback, which might further lead to maladaptive mental states.

Local resection versus radical resection after neoadjuvant chemoradiotherapy for patients with locally advanced rectal cancer: a propensity-score matched cohort analysis.

BACKGROUND: We aimed to address the shortage of evidence regarding the safety of the local resection approach by comparing long-term oncological outcomes between patients managed by local resection and those who underwent radical resection. METHODS: This was a propensity-score matched cohort analysis study that included patients of all ages diagnosed with locally advanced rectal cancer (LARC) who had received neoadjuvant chemoradiotherapy (nCRT) at the Fujian Medical University Union Hospital and Fujian Medical University Affiliated Zhangzhou Hospital, China, between Jan 10, 2011, to Dec 28, 2021. Partial patients with a significant downstage of the tumor were offered management with the local resection approach, and most of the rest were offered radical resection if eligible. FINDINGS: One thousand six hundred ninety-three patients underwent radical resection after nCRT, and another 60 patients performed local resection. The median follow-up times were 44.0 months (interquartile range = 4-107 months). After propensity-core matching (PSM), in the Kaplan-Meier curves, local resection (n = 56) or radical resection (n = 211) was not significantly associated with 1-, 3-, and 5-year cumulative incidence of overall survival (OS) (HR = 1.103, 95% CI: 0.372 ~ 3.266), disease-free survival (DFS) ((HR = 0.972, 95% CI: 0.401 ~ 2.359), local recurrence (HR = 1.044, 95% CI: 0.225 ~ 4.847), and distant metastasis (HR = 0.818, 95% CI: 0.280 ~ 2.387) (all log-rank P > 0.05). Similarly, multivariate Cox regression analysis indicates that local excision still was not an independent risk factor for OS (HR = 0.863, 95% CI: 0.267 ~ 2.785, P = 0.805) and DFS (HR = 0.885, 95% CI: 0.353 ~ 2.215, p = 0.794). CONCLUSION: Local resection can be a management option in selected patients with middle-low rectal cancer after nCRT for LARC and without loss of oncological safety at five years.

Enhancing Prosthetic Control through High-Fidelity Myoelectric Mapping with Molecular Anchoring Technology.

Myoelectric control utilizes electrical signals generated from the voluntary contraction of remaining muscles in an amputee's stump to operate a prosthesis. Precise and agile control requires low-level myoelectric signals (below 10% of maximum voluntary contraction, MVC) from weak muscle contractions such as phantom finger or wrist movements, but imbalanced calcium concentration in atrophic skin can distort the signals. This is due to poor ionic-electronic coupling between skin and electrode, which often causes excessive muscle contraction, fatigue, and discomfort during delicate tasks. To overcome this challenge, a new strategy called molecular anchoring is developed to drive hydrophobic molecular effectively interact with and embed into stratum corneum for high coupling regions between ionic fluxes and electronic currents. The use of hydrophobic poly(N-vinyl caprolactam) gel has resulted in an interface impedance of 20 kΩ, which is 1/100 of a commercial acrylic-based electrode, allowing the detection of ultralow myoelectric signals (≈1.5% MVC) that approach human limits. With this molecular anchoring technology, amputees operate a prosthesis with greater dexterity, as phantom finger and wrist movements are predicted with 97.6% accuracy. This strategy provides the potential for a comfortable human-machine interface when amputees accomplish day-to-day tasks through precise and dexterous myoelectric control.

Hair Cortisone Predicts Lower Stress-induced Salivary Cortisol Response: Resting-state Functional Connectivity Between Salience and Limbic Networks.

Previous studies revealed that high long-term hypothalamic-pituitaryadrenal (HPA) axis activity measured by the hair cortisol concentrations predicts lower acute stress cortisol response and reported the influences of hair cortisol on brain activity during acute stress exposure. However, considering that long-term HPA axis activity has a close relationship with the brain's resting-state functional connectivity (RSFC), the current study aimed to explore the role of RSFC between limbic and salience network in this relationship. Seventy-seven healthy participants underwent resting-state imaging scans before performing the acute ScanSTRESS task. Saliva samples were collected to assess the levels of acute stress salivary cortisol. Hair samples were also collected, and the corticosteroid concentration extracted from these samples were used as a biomarker of long-term HPA axis activity. High hair cortisone (HairE) levels predicted lower acute stress cortisol response. Moreover, high HairE levels were significantly correlated with enhanced RSFC between limbic and salience networks, while RSFC was negatively associated with acute stress cortisol response. Importantly, the RSFC between left insula and left parahippocampus mediated the association between HairE and acute cortisol stress response. Taken together, this study uncovers the important role of RSFC between salience and limbic networks in the long-term relationship between HairE and acute cortisol response and contributes to a deeper understanding of the individual differences in acute stress response.

Differential diagnostic performance of PET/CT in adult-onset still's disease and lymphoma: a retrospective pilot study.

Background: Adult-onset still's disease (AOSD) and lymphoma are the common causes of fever of unknown origin (FUO) and show some similar clinical symptoms. This study aimed to establish a reliable and easy-to-used scoring model based on clinical information, laboratory characteristics and 18F-fluorodeoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) images for the differential diagnosis of these two diseases. Methods: A development cohort including 70 AOSD and 37 lymphoma patients was used to establish a scoring model based on the features of PET/CT images. The scoring model was then validated in a validation cohort of 15 AOSD and 12 lymphoma patients. The features of involved bone marrow, spleen, lymph nodes, and other organs or tissues displayed on PET/CT images were compared. Multiple logistics regression and decision tree analysis were used to establish the scoring model. Results: Four features that could significantly differentiate these two diseases were selected to establish a scoring model discriminating AOSD from lymphoma, including (I) white blood cell (WBC) count ≤10×109/L (1 point); (II) ferritin ≤ upper limit of normal (ULN) (1 point); (III) no abnormal bone marrow metabolism (1 point); (IV) total lesion glycolysistotal (TLGtotal) >9.0 (1 point). After decision tree analysis, it showed that a score ≤1 indicates AOSD. A score ≥3 strongly suggested lymphoma, with a sensitivity of 81.1% and specificity of 90.0% in the development cohort, and a sensitivity of 58.3% and specificity of 100% in the validation cohort. Conclusions: Our scoring model showed good diagnosis performance in distinguishing AOSD from lymphoma.

Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways.

Glucagon has emerged as a key regulator of extracellular amino acid (AA) homeostasis. Insufficient glucagon signaling results in hyperaminoacidemia, which drives adaptive proliferation of glucagon-producing α cells. Aside from mammalian target of rapamycin complex 1 (mTORC1), the role of other AA sensors in α cell proliferation has not been described. Here, using both genders of mouse islets and glucagon receptor (gcgr)-deficient zebrafish (Danio rerio), we show α cell proliferation requires activation of the extracellular signal-regulated protein kinase (ERK1/2) by the AA-sensitive calcium sensing receptor (CaSR). Inactivation of CaSR dampened α cell proliferation, which was rescued by re-expression of CaSR or activation of Gq, but not Gi, signaling in α cells. CaSR was also unexpectedly necessary for mTORC1 activation in α cells. Furthermore, coactivation of Gq and mTORC1 induced α cell proliferation independent of hyperaminoacidemia. These results reveal another AA-sensitive mediator and identify pathways necessary and sufficient for hyperaminoacidemia-induced α cell proliferation.

Development and validation of neoadjuvant rectal score-based signature nomograms to predict overall survival and disease-free survival in locally advanced rectal cancer: a retrospective, double center, cohort study.

AIM: To evaluate the prognostic significance of the NAR score and develop nomograms for locally advanced rectal cancer (LARC) treated after neoadjuvant chemo-radiotherapy (nCRT) combined with total meso-rectal excision (TME) surgery to predict prognostic. METHODS: Retrospective collection among LARC patients treated at Fujian Medical University Union Hospital (training cohort) and Fujian Medical University Affiliated Zhangzhou Hospital (external validation cohort) between Jan 10, 2011 and Dec 28, 2021. The NAR score was calculated by formula: [5pN-3(cT-pT) + 12]^2/9.61. NAR score low (< 8), intermediate (8-16), and high (> 16). RESULTS: 1665 patients in the training cohort and 256 patients in the external validation cohorts were enrolled. Lower NAR score was significantly associated with better cumulative incidence of OS, DFS, local recurrence (LR), and distant metastasis (DM) (all P < 0.001). Multivariate Cox regression analysis indicates that NAR score, distance to the anal verge, no.253 LN metastasis, post-CRT carbohydrate antigen 19-9, tumor regression grade, and surgery method are independent predictors of OS and DFS (all P < 0.001). Among these independent factors, the NAR score had the highest area under the curve (AUC) and the nomograms to predict OS and DFS were generated. The AUCs for the accuracy of the prediction OS were 1 year = 0.742, 3 years = 0.749, 5 years = 0.713; prediction DFS were 1 year = 0.727, 3 years = 0.739, 5 years = 0.718, the models have good accuracy. CONCLUSIONS: The NAR score can effectively classify patients with LARC into groups with varying outcomes of OS, DFS, LR, and DM. Moreover, the novel nomograms comprising the NAR score were developed and validated to help predict OS and DFS.

Inactivated SARS-CoV-2 vaccine does not increase the risk of relapse in patients with clinically inactive adult-onset Still's disease.

OBJECTIVE: A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. METHODS: We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBP-CorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period, and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. RESULTS: A total of 122 patients with inactive AOSD were included, of which 49.2% (n = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% vs 6.8%), and no relapse occurred within 1 month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. CONCLUSION: Increased disease activity or relapse following vaccination with inactivated SARS-CoV-2 was rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS-CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2.