Self-healing polyacrylates based on dynamic disulfide and quadruple hydrogen bonds.

Herein, a self-healing polyacrylate system was successfully prepared by introducing crosslinking agents containing disulfide bonds and monomers capable of forming quadruple hydrogen bonds through free radical copolymerization. This polymer material exhibited good toughness and self-healing properties through chemical and physical dual dynamic networks while maintaining excellent mechanical properties, which expanded the development path of self-healing acrylate materials. Compared to uncrosslinked and single dynamically crosslinked polymers, its elongation at break was as high as 437%, and its tensile strength was 5.48 MPa. Due to the presence of dual reversible dynamic bonds in the copolymer system, good self-healing was also achieved at 60 °C. In addition, differential scanning calorimetry and thermogravimetric analysis measurements confirmed that the thermal stability and glass transition temperature of the material were improved owing to the presence of physical and chemical cross-linking networks.

Self-adaptive pyroptosis-responsive nanoliposomes block pyroptosis in autoimmune inflammatory diseases.

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the N-terminal domain of gasdermin E, selectively integrates with the cardiolipin of liposomes, thus forming pores for controlled drug release, pyroptosis, and inflammation inhibition. Therefore, RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice. Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery, suppressing pyroptosis and treating autoimmune inflammatory diseases.

Association between haemoglobin-to-red blood cell distribution width ratio at admission and all-cause mortality in adult patients with sepsis in an intensive care unit: a secondary analysis of the MIMIC-IV database.

OBJECTIVE: The association between haemoglobin-to-red blood cell distribution width ratio (HRR) and all-cause mortality remains poorly understood. This study aimed to examine the influence of HRR at the time of admission mortality over 1 year and 30 days in patients with sepsis. DESIGN: This was a secondary analysis. SETTING: This study was conducted in intensive care units (ICUs). PARTICIPANTS: Adult patients with sepsis were identified and included from an intensive care database based on eligibility criteria. PRIMARY OUTCOME AND MEASURE: The primary outcome was the rate of death within 1 year. The secondary outcome was the death rate within 30 days. RESULTS: A total of 4233 patients with sepsis who met the inclusion criteria were analysed, excluding those ineligible. These participants were divided into quartiles based on their HRR at admission. The overall mortality rates at 1 year and 30 days were 42.9% and 25.5%, respectively. A significant inverse association was observed between HRR quartiles and all-cause mortality (p<0.001). Pairwise comparisons using Kaplan-Meier analysis showed significant differences in 1-year mortality rates across the quartiles. However, no significant difference was detected in 30-day mortality between the Q3 and Q4 groups (p=0.222). Multivariate Cox regression analysis demonstrated that a higher HRR at ICU admission was independently associated with reduced mortality at 1 year (HR, 0.935; 95% CI 0.913 to 0.958; p<0.001) and 30 days (HR, 0.969; 95% CI 0.939 to 0.999; p=0.043). Furthermore, restricted cubic spline models indicated a non-linear relationship between HRR and mortality at both 1 year and 30 days (p<0.001 for both). CONCLUSIONS: This retrospective analysis demonstrated that the HRR at the time of admission was a significant prognostic marker for long-term mortality in patients with sepsis.

A review of nanomaterials for biosensing applications.

A biosensor is a device that reacts with the analyte to be analyzed, detects its concentration, and generates readable information, which plays an important role in medical diagnosis, detection of physiological indicators, and disease prevention. Nanomaterials have received increasing attention in the fabrication and improvement of biosensors due to their unique physicochemical and optical properties. In this paper, the properties of nanomaterials such as the size effect, optical and electrical properties, and their advantages in the field of biosensing are briefly summarized, and the application of nanomaterials can effectively improve the sensitivity and reduce the detection limit of biosensors. The advantages of commonly used nanomaterials such as gold nanoparticles (AuNPs), carbon nanotubes (CNTs), quantum dots (QDs), graphene, and magnetic nanobeads for biosensor applications are also reviewed. Besides, the two main types of biosensors using nanomaterials involved in their construction and their working principles are described, and the toxicity and biocompatibility of nanomaterials and the future direction of nanomaterial biosensors are discussed.

Nomogram for predicting major bleeding after off-pump coronary artery bypass grafting.

OBJECTIVE: The purpose of this investigation is to develop a novel nomogram for predicting major bleeding following off-pump coronary artery bypass grafting (CABG). METHODS: Between January 2012 and December 2022, 541 patients who underwent off-pump isolated primary CABG were included in a retrospective analysis. The primary outcome measure after off-pump CABG was major bleeding. Based on the outcomes of a multivariate analysis, nomograms were constructed. Using receiver operating characteristic analysis and calibration, the predictive accuracy of the nomograms was assessed. Using decision curve analysis (DCA), the clinical benefit of the nomograms was determined. RESULTS: We categorized 399 and 142 patients in the "no major bleeding group" and "major bleeding group", respectively. Age (odds ratio (OR) 1.038; 95% confidence interval (CI) 1.009-1.068; p = 0.009), body mass index (OR 0.913; 95% CI 0.849-0.982; p = 0.014), hemoglobin (OR 0.958; 95% CI 0.945-0.971; p < 0.001), sodium (OR 0.873; 95% CI 0.807-0.945; p = 0.001), blood urea nitrogen (OR 1.198; 95% CI 1.073-1.338; p = 0.001), and operation time (OR 1.012; 95% CI 1.008-1.017; p < 0.001) were independent predictors for major bleeding after off-pump CABG. The model based on independent predictors exhibited excellent discrimination and calibration, with good agreement between actual and nomogram-estimated probabilities of generalization. DCA demonstrated that nomogram-assisted decisions have a greater positive benefit than treating all patients or none. CONCLUSIONS: The plotted nomogram accurately predicted major bleeding outcomes following off-pump CABG and may therefore contribute to clinical decision-making, patient treatment, and consultation services.

Fully integrated wearable microneedle biosensing platform for wide-range and real-time continuous glucose monitoring.

Wearable microneedle sensors for continuous glucose monitoring (CGM) have great potential for clinical impact by allowing access to large data sets to provide individualized treatment plans. To date, their development has been challenged by the accurate wide linear range tracking of interstitial fluid (ISF) glucose (Glu) levels. Here, we present a CGM platform consisting of a three-electrode microneedle electrochemical biosensor and a fully integrated radio-chemical analysis system. The long-term performance of the robust CGM on diabetic rats was achieved by electrodepositing Prussian blue (PB), and crosslinking glucose oxidase (GOx) and chitosan to form a 3D network using glutaraldehyde (GA). After redox by GOx, PB rapidly decomposes hydrogen peroxide and mediates charge transfer, while the 3D network and graphite powder provide enrichment and release sites for Glu and catalytic products, enabling a sensing range of 0.25-35 mM. Microneedle CGM has high sensitivity, good stability, and anti-interference ability. In diabetic rats, CGM can accurately monitor Glu levels in the ISF in real-time, which are highly consistent with levels measured by commercial Glu meters. These results indicate the feasibility and application prospects of the PB-based CGM for the clinical management of diabetes. STATEMENT OF SIGNIFICANCE: This study addresses the challenge of continuous glucose monitoring system design where the narrow linear range of sensing due to the miniaturization of sensors fails to meet the monitoring needs of clinical diabetic patients. This was achieved by utilizing a three-dimensional network of glutaraldehyde cross-linked glucose oxidase and chitosan. The unique topology of the 3D network provides a large number of sites for glucose enrichment and anchors the enzyme to the sensing medium and the conductive substrate through covalent bonding, successfully blocking the escape of the enzyme and the sensing medium and shortening the electron transfer and transmission path.

Biomass-derived 2D carbon materials: structure, fabrication, and application in electrochemical sensors.

Biomass, a renewable hydrocarbon, is one of the favorable sources of advanced carbon materials owing to its abundant resources and diverse molecular structures. Biomass-based two-dimensional carbon nanomaterials (2D-BC) have attracted extensive attention due to their tunable structures and properties, and have been widely used in the design and fabrication of electrochemical sensing platforms. This review embarks on the thermal conversion process of biomass from different sources and the synthesis strategy of 2D-BC materials. The affinity between 2D-BC structure and properties is emphasized. The recent progress in 2D-BC-based electrochemical sensors for health and environmental monitoring is also presented. Finally, the challenges and future development directions related to such materials are proposed in order to promote their further application in the field of electrochemical sensing.

Artificial intelligence in global health equity: an evaluation and discussion on the application of ChatGPT, in the Chinese National Medical Licensing Examination.

Background: The demand for healthcare is increasing globally, with notable disparities in access to resources, especially in Asia, Africa, and Latin America. The rapid development of Artificial Intelligence (AI) technologies, such as OpenAI's ChatGPT, has shown promise in revolutionizing healthcare. However, potential challenges, including the need for specialized medical training, privacy concerns, and language bias, require attention. Methods: To assess the applicability and limitations of ChatGPT in Chinese and English settings, we designed an experiment evaluating its performance in the 2022 National Medical Licensing Examination (NMLE) in China. For a standardized evaluation, we used the comprehensive written part of the NMLE, translated into English by a bilingual expert. All questions were input into ChatGPT, which provided answers and reasons for choosing them. Responses were evaluated for "information quality" using the Likert scale. Results: ChatGPT demonstrated a correct response rate of 81.25% for Chinese and 86.25% for English questions. Logistic regression analysis showed that neither the difficulty nor the subject matter of the questions was a significant factor in AI errors. The Brier Scores, indicating predictive accuracy, were 0.19 for Chinese and 0.14 for English, indicating good predictive performance. The average quality score for English responses was excellent (4.43 point), slightly higher than for Chinese (4.34 point). Conclusion: While AI language models like ChatGPT show promise for global healthcare, language bias is a key challenge. Ensuring that such technologies are robustly trained and sensitive to multiple languages and cultures is vital. Further research into AI's role in healthcare, particularly in areas with limited resources, is warranted.

Subverted macrophages in the triple-negative breast cancer ecosystem.

Tumor-associated macrophages (TAMs) are the most critical effector cells of innate immunity and the most abundant tumor-infiltrating immune cells. They play a key role in the clearance of apoptotic bodies, regulation of inflammation, and tissue repair to maintain homeostasis in vivo. With the progression of triple-negative breast cancer（TNBC）, TAMs are "subverted" from tumor-promoting immune cells to tumor-promoting immune suppressor cells, which play a significant role in tumor development and are considered potential targets for cancer therapy. Here, we explored how macrophages, as the most important part of the TNBC ecosystem, are "subverted" to drive cancer evolution and the uniqueness of TAMs in TNBC progression and metastasis. Similarly, we discuss the rationale and available evidence for TAMs as potential targets for TNBC therapy.

Clinical characterization of EFHD2 (swiprosin-1) in Glioma-associated macrophages and its role in regulation of immunosuppression.

Glioblastoma has been extensively studied due to its high mortality and short survival. The evolution mechanism of tumor-associated macrophages (TAMs) to Glioma-associated microglia and macrophages (GAMs) in the tumor microenvironment (TME) remains to be elucidated. The tumor cell-to-cell interaction patterns have not been well defined yet. The EF-Hand Domain Family Member D2 (EFHD2) has been reported to be differentially expressed as an immunomodulatory molecule in a variety of cancers. But large-scale clinical data from multiple ethnic communities have not been used to investigate the role of EFHD2 in glioma. RNA-seq data from 313 or 657 glioma patients from the Chinese Glioma Genome Atlas (CGGA) database and 603 glioma patients from the Cancer Genome Atlas (TCGA) database were analyzed retrospectively. Cell localization was performed using single-cell sequencing data from the CGGA database and the GSE131928 dataset. Mouse glioma cell lines and primary macrophages isolated from Efhd2 knockout mice were co-cultured to validate the immunomodulatory effects of EFHD2 on macrophages and the remodeling of TME of glioblastoma. EFHD2 is enriched in high-grade gliomas, isocitrate dehydrogenase wild-type, and 1p/19q non-co-deficient gliomas. It is a potential biomarker of glioma-proneuronal subtypes and an independent prognostic factor for overall survival in patients with malignant glioblastoma. EFHD2 regulates the monocyte-macrophage system function and positively correlates with immunosuppressive checkpoints. Further experimental data demonstrates that Efhd2 influences the polarization state of GAMs and inhibits the secretion of TGF-ß1. In vitro experiments have revealed that macrophages lacking Efhd2 suppress the vitality of two glioma cell lines and decelerate the growth of glioma xenografts. In conclusion, EFHD2 promises to be a key target for TME-related immunotherapy.

Numerical Study on the Seismic Performance of Cold-Formed Steel Shear Walls with Steel Sheathing and Gypsum Board.

The cold-formed steel shear wall with steel sheathing has gained increasing popularity due to its excellent shear capacity. To extend the applicability of this system to multi-story residences, aside from experimental investigations on the shear walls, it is essential to conduct a comprehensive study on the seismic performance of buildings. In this paper, numerical simulations were conducted on specimens subjected to monotonic and cyclic loading. Subsequently, seismic analysis of mid-rise building models was also carried out to investigate the influence of the proposed shear wall on building seismic performance. The research findings indicate that this study's modeling method can effectively simulate the shear performance of the proposed shear wall under monotonic and cyclic loading. In addition, the proposed shear wall significantly enhances the structural stiffness and improves the seismic performance of the structure under seismic action.

Organising pneumonia caused by hormone (tamoxifen) therapy after radiotherapy for breast cancer: a case report and review of the literature.

Background: Five-year treatment with tamoxifen (TAM) has been the traditional standard of care for breast cancer. Organising pneumonia (OP) is a rare but significant complication of radiation therapy for breast cancer. The effect of TAM leading to OP has not yet been clearly documented. Case Description: This report describes the case of a 38-year-old female who developed progressive aggravation of round-like patchy bilateral pulmonary infiltrated with a reverse halo sign but without any clinical symptoms 5 months after TAM therapy, following breast-conserving surgery and radiotherapy (RT) for breast carcinoma. A lung biopsy was performed and revealed a histological pattern of OP. TAM therapy was discontinued, and subsequent gradual radiological improvement was observed. As there was no proof for TAM had caused the incident, TAM was re-administrated. Eight months after reinstitution of TAM, the same patchy migratory bilateral pulmonary infiltrated with reverse halo sign was found on chest CT with the patient claiming no discomforts nor any clinical symptoms. The diagnosis of TAM-related OP was made based on the exclusion of other causes and recurrence with the re-administration of TAM. The multidisciplinary team (MDT) concluded that TAM should be withdrawn and a "wait-and-see" approach was taken after a comprehensive assessment, instead of altering the medication or performing prophylactic mastectomy. Conclusions: The withdrawal and rechallenge of TAM strongly suggest that it may play a role as a cofactor in the occurrence of OP after RT for breast cancer, and RT may also be a cofactor in the occurrence of OP. It is extremely important to be alerted to the possibility of OP after concurrent or sequential hormonal therapy and RT.

Corrigendum: Curcumin alleviates experimental colitis in mice by suppressing necroptosis of intestinal epithelial cells.

[This corrects the article DOI: 10.3389/fphar.2023.1170637.].

Effect of Erector Spinae Plane Block in Terms of Analgesic Efficacy in Elderly Patients Undergoing Posterior Lumbar Spine Surgery: A Retrospective, Propensity-Score Matched Study.

INTRODUCTION: For preoperative analgesia during a variety of operations, the erector spinae plane block (ESPB) has grown in popularity. However, its effectiveness in lumbar surgery is still unknown. The purpose of this study was to investigate the potential benefits of ESPB in enhancing analgesic efficacy in elderly individuals following posterior lumbar spine surgery. METHODS: Patients aged 65 years or older who underwent elective posterior lumbar instrumented fusion (with or without decompression) at our institution between January 2019 and June 2022 were included. Demographic data, comorbidities, and results of preoperative screening were retrospectively collected. Propensity score matching (PSM) was performed in a ratio of 1:1 for control and ESPB groups. The primary outcome was opioid consumption at 24 h after surgery. Secondary outcomes was visual analog scale (VAS) pain scores at rest in the first 24 h. Additional secondary outcomes included number of patients requesting rescue analgesia, incidence of nausea and vomiting, time to the first request for analgesia via patient-controlled analgesia, and length of stay. RESULTS: A total of 382 patients were included, of whom 119 received ESPB. The mean age of the study patients was 70.6 years old, and 254 (66.5%) were male. After PSM, each group comprised 115 patients. Patients in the ESPB group showed a significantly lower opioid consumption at 24 h after surgery. Compared with the control group, VAS pain scores at rest in the first 24 h, number of patient-controlled intravenous analgesia (PCIA) pump compressions, ratio of patients requesting rescue analgesia, incidence of nausea and vomiting, and length of stay were significantly reduced in the ESPB group. There were no significant differences between the two groups regarding safety outcomes. CONCLUSIONS: ESPB reduces short-term opioid consumption while providing safe and effective analgesia in elderly patients undergoing posterior lumbar surgery.

Programmed death of intestinal epithelial cells in neonatal necrotizing enterocolitis: a mini-review.

Necrotizing enterocolitis (NEC) is one of the most fatal diseases in premature infants. Damage to the intestinal epithelial barrier (IEB) is an important event in the development of intestinal inflammation and the evolution of NEC. The intestinal epithelial monolayer formed by the tight arrangement of intestinal epithelial cells (IECs) constitutes the functional IEB between the organism and the extra-intestinal environment. Programmed death and regenerative repair of IECs are important physiological processes to maintain the integrity of IEB function in response to microbial invasion. However, excessive programmed death of IECs leads to increased intestinal permeability and IEB dysfunction. Therefore, one of the most fundamental questions in the field of NEC research is to reveal the pathological death process of IECs, which is essential to clarify the pathogenesis of NEC. This review focuses on the currently known death modes of IECs in NEC mainly including apoptosis, necroptosis, pyroptosis, ferroptosis, and abnormal autophagy. Furthermore, we elaborate on the prospect of targeting IECs death as a treatment for NEC based on exciting animal and clinical studies.

Curcumin alleviates experimental colitis in mice by suppressing necroptosis of intestinal epithelial cells.

Curcumin, the primary bioactive substance in turmeric, exhibits potential therapeutic effects on ulcerative colitis. However, its mechanism for regulating necroptosis in colitis has not been fully elucidated. In this study, the effect of curcumin on experimental colitis-induced necroptosis of intestinal epithelial cells was investigated, and its molecular mechanism was further explored. We found that curcumin blocked necroptosis in a dose-dependent manner by inhibiting the phosphorylation of RIP3 and MLKL instead of RIP1 in HT-29 cells. Co-Immunoprecipitation assay showed that curcumin weakened the interaction between RIP1 and RIP3, possibly due to the direct binding of curcumin to RIP3 as suggested by drug affinity responsive target stability analysis. In a classical in vivo model of TNF-α and pan-caspase inhibitor-induced necroptosis in C57BL/6 mice, curcumin potently inhibited systemic inflammatory responses initiated by the necroptosis signaling pathway. Then, using a dextran sodium sulfate-induced colitis model in C57BL/6 mice, we found that curcumin inhibited the expression of p-RIP3 in the intestinal epithelium, reduced intestinal epithelial cells loss, improved the function of the intestinal tight junction barrier, and reduced local intestinal inflammation. Collectively, our findings suggest that curcumin is a potent targeted RIP3 inhibitor with anti-necroptotic and anti-inflammatory effects, maintains intestinal barrier function, and effectively alleviates colitis injury.

A Knitted PET Patch Enhances the Maturation of Regenerated Tendons in Bridging Reconstruction of Massive Rotator Cuff Tears in a Rabbit Model.

BACKGROUND: Although nondegradable synthetic grafts for bridging reconstruction of massive rotator cuff tears (MRCTs) have shown satisfactory clinical outcomes, their function and details on graft-tendon healing and enthesis regeneration have not been fully studied. HYPOTHESIS: The knitted polyethylene terephthalate (PET) patch as a nondegradable synthetic graft could provide sustained mechanical support, facilitating enthesis and tendon regeneration in the treatment of MRCTs. STUDY DESIGN: Controlled laboratory study. METHODS: A knitted PET patch was fabricated for bridging reconstruction (PET group) in a New Zealand White rabbit model of MRCTs (negative control group), and an autologous Achilles tendon was used as a control (autograft group). The animals were sacrificed, and tissue samples were harvested for gross observation as well as histological and biomechanical analyses at 4, 8, and 12 weeks postoperatively. RESULTS: Histological analysis showed no significant difference in the graft-bone interface score between the PET and autograft groups at 4, 8, and 12 weeks postoperatively. Interestingly, in the PET group, Sharpey-like fibers were observed at 8 weeks, while fibrocartilage formation and the ingrowth of chondrocytes were recognized at 12 weeks. Meanwhile, the tendon maturing score was significantly higher in the PET group than in the autograft group (19.7 ± 1.5 vs 15.3 ± 1.2, respectively; P = .008) at 12 weeks, with parallel-oriented collagen fibers around the knitted PET patch. Moreover, the ultimate failure load of the PET group was similar to that of a healthy rabbit tendon at 8 weeks (125.6 ± 13.6 vs 130.8 ± 28.6 N, respectively; P > .05) and no different from that of the autograft group at 4, 8, and 12 weeks. CONCLUSION: The knitted PET patch could not only immediately reconstruct the mechanical support for the torn tendon postoperatively in the rabbit model of MRCTs but also enhanced maturation of the regenerated tendon by fibrocartilage formation and improved the organization of collagen fibers. Herein, the knitted PET patch could be a promising candidate graft adopted in bridging reconstruction of MRCTs. CLINICAL RELEVANCE: A nondegradable knitted PET patch can safely bridge MRCTs with satisfactory mechanical strength and the promotion of tissue regeneration.

Functional and Structural Outcomes After Arthroscopic Rotator Cuff Repair With or Without Preoperative Corticosteroid Injections.

BACKGROUND: Corticosteroid injections (CSIs) are effective in alleviating pain in patients with rotator cuff tears, but controversy still exists regarding their potential adverse effects on clinical outcomes after rotator cuff repair. PURPOSE: To compare both the functional and the structural outcomes in patients who underwent arthroscopic rotator cuff repair with or without preoperative CSIs. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective cohort study was carried out among patients who underwent arthroscopic rotator cuff repair for partial- and full-thickness tears between 2015 and 2019. The patients who received preoperative CSIs were included in the CSI group and compared with a group without preoperative CSIs (non-CSI group), matched at a ratio of 1:2 based on tear size, age, and follow-up time. Both functional evaluation and structural assessments using magnetic resonance imaging (MRI) were performed at the final follow-up. Clinical outcomes-including retear rate as the primary outcome; pain; functional scores including the Constant-Murley score, American Shoulder and Elbow Surgeons score, and Fudan University Shoulder Score; range of motion (ROM); tendon integrity; tendon healing type; and cartilage thickness-were compared between the 2 groups with a statistical significance of P < .05 and power of 0.9. RESULTS: Thirty-one patients were included in the CSI group, and 62 were included in the non-CSI group. After a mean 3-year follow-up, the 2 groups demonstrated no significant differences in retear rate; visual analog scale for pain; shoulder functional scores; and active ROM including forward flexion, abduction, external rotation, and internal rotation. No significant differences were observed on postoperative MRI scans of the rotator cuff tendon (tendon integrity, healing type, residual tendon attachment area, etc), cartilage thickness, and muscle atrophy. CONCLUSION: No significant differences were found at a mean 3-year follow-up in the retear rates, pain, ROM, and glenohumeral structure on postoperative MRI scans after arthroscopic rotator cuff repair with or without preoperative CSIs.

Enhanced red blood cell distribution width to platelet ratio is a predictor of mortality in patients with sepsis: a propensity score matching analysis based on the MIMIC-IV database.

OBJECTIVE: To explore the association between dynamic changes in red blood cell distribution width to platelet count ratio (RPR) during hospitalisation and short-term mortality in patients with sepsis. DESIGN: A retrospective cohort study using propensity score matching. SETTING: Intensive care units (ICUs) of Beth Israel Deaconess Medical Center. PARTICIPANTS: A total of 8731 adult patients with sepsis were included in the study. The patients were identified from the ICU of the Medical Information Mart for Intensive Care database. The observed group included patients who experienced an increase in RPR of more than 30% during the first week of ICU admission, whereas the control group included the rest. MAIN OUTCOME AND MEASURE: Using propensity score matching, a matched control group was created. The primary outcome was 28-day mortality, and the length of hospital stay and in-hospital mortality were the secondary outcomes. RESULTS: The difference was evident in 28-day mortality between the two groups (85.8% vs 74.5%, p<0.001, Kaplan-Meier analysis, and HR=1.896, 95% CI=1.659 to 2.168, p<0.001, Cox regression). In the secondary outcomes, there was a significant difference in in-hospital mortality (p<0.001). In addition, the study discovered that the observed groups had a significantly longer hospital stay (p<0.001). Meanwhile, the results of subgroup analyses were consistent with those of the primary analyses. CONCLUSIONS: In patients with sepsis, a significantly increased RPR is positively associated with the short-term death rate. Continuous RPR monitoring could be a valuable measure for predicting short-term mortality in patients with sepsis.

Clinicopathological features and prognosis of bilateral breast cancer: a single-center cohort study based on Chinese data.

Background: The incidence of bilateral breast cancer (BBC) is low, accounting for 5% of patients with breast cancer. This study aimed to investigate the clinicopathological features and prognosis of synchronous bilateral breast cancer (SBBC) and metachronous bilateral breast cancer (MBBC) in the Chinese population. Methods: Patients with BBC, including SBBC and MBBC, were selected from 6,162 breast cancer patients who underwent surgery at the Chinese People's Liberation Army (PLA) General Hospital between January 2007 and December 2019. Furthermore, patients with unilateral breast cancer (UBC) who underwent surgery at the same time were randomly selected at a ratio of 1:2 as the control group. Clinicopathological features and prognosis were compared between the groups. Results: In all, 123 (2.0%) patients with BBC were enrolled in this study, including 98 (1.6%) SBBC and 25 (0.4%) MBBC patients. A total of 280 patients with UBC were selected for the control group. Compared with patients with UBC, patients with SBBC were more likely to be older and have a family history of breast cancer, non-infiltrative carcinoma, lower pathological tumor-node-metastasis (pTNM) stage, and luminal A type breast cancer as their first tumor. Patients with MBBC were more likely to be postmenopausal and have hormone receptor [estrogen receptor (ER)/progesterone receptor (PR)] negativity, a higher pTNM stage, and a triple-negative first tumor. Patients with UBC with ER/PR (-) were more likely to develop contralateral breast cancer (CBC) than those with ER/PR (+). There was no significant difference in overall survival (OS) and disease-free survival (DFS) between patients with SBBC and patients with UBC. Patients with MBBC had worse DFS than those with UBC, but OS was similar for both types of patients. Patients with MBBC <55 years at first diagnosis had significantly shorter DFS compared to those with SBBC and UBC. A multivariate Cox proportional hazards model revealed that age ≥55 years and ER/PR negativity of the first tumor were independent risk factors for OS. Independent risk factors for DFS included MBBC, age <55 years, family history of other malignant tumors, ER/PR (-), lymphovascular invasion, and N stage ≥2 of the first tumor. Conclusions: The OS and DFS of patients with SBBC and UBC were similar. The MBBC patients, especially those <55 years old at first diagnosis, had shorter DFS than patients with UBC.