Multicenter Cohort Research Articles

Transarterial chemoembolization combined with lenvatinib plus tislelizumab for unresectable hepatocellular carcinoma: a multicenter cohort study.

Comparing the efficacy of transarterial chemoembolization (TACE) combined with lenvatinib plus tislelizumab (TLT) with TACE combined with lenvatinib (TL) for unresectable hepatocellular carcinoma, particularly in determining which patients can benefit more from the TLT treatment. From March 2021 to September 2023, a total of 169 patients from three centers were included in this study, with 103 patients receiving TLT and 66 patients receiving TL. The Kaplan-Meier method was utilized to evaluate the cumulative overall survival (OS) and progression-free survival (PFS) between the two groups and were assessed using the log-rank test. Subgroup analysis on tumor number, maximum tumor diameter, presence of portal vein thrombosis, AFP level, and Child-Pugh class were conducted. The median OS was 26 months in the TLT group, and 20 months in the TL group. The median PFS was 14 months in the TLT group and 9 months in the TL group. The Kaplan-Meier curve demonstrated a significantly superior OS and PFS in the TLT group compared to the TL group. Subgroup analysis showed that for patients with a maximum tumor diameter greater than 7 cm, AFP > 400 ng/ml and accompanied by portal vein tumor thrombus, and Child-Pugh class A, there was a statistically significant difference in OS between TLT and TL groups. OS and PFS were significantly improved in patients who received TLT compared to those who received TL, patients with a largest tumor diameter greater than 7 cm, AFP > 400 ng/ml, Child-Pugh class A and PVTT appeared to derive more benefit.

Hyperchloremic metabolic acidosis potentially benefiting sodium bicarbonate therapy: A multi-center cohort study

BackgroundThe use of sodium bicarbonate for metabolic acidosis has been a topic of debate, primarily due to the lack of clinical efficacy evidence. This study aims to identify which types of patients with various acid-base balance parameters can benefit from sodium bicarbonate therapy. MethodsPatients diagnosed with metabolic acidosis were screened from a large multi-center critical care database to form a retrospective cohort. Mortality curves, logistic regression analysis, simulation methods, and propensity scores were used to compare data between sodium bicarbonate (SOB group) and non-treated (Non-SOB group) patients. ResultsThere was an interaction between baseline chloride, anion gap levels and sodium bicarbonate therapy on patients' in-hospital death. As chloride levels increased, the in-hospital mortality curves of the SOB group and Non-SOB group gradually converged, with the difference narrowing from approximately 20 % to 10 %, and then gradually widened with the increase of the anion gap. Furthermore, when patients had high chloride levels (≥112 mmol/L), those in the SOB group exhibited a higher incidence of hypernatremia, hypokalemia, and hypocalcemia at 24 h, and a lower incidence of hyperchloremia. Patients in SOB group also had a lower simulated mortality. Among patients treated with sodium bicarbonate, those with low chloride had more difficulty in normalizing pH compared to those with high chloride. ConclusionsThis study identified an interaction between baseline chloride and sodium bicarbonate therapy on patient survival. Hyperchloremic metabolic acidosis may potentially benefit from sodium bicarbonate therapy. Further prospective randomized controlled studies are warranted.

The impact of admitting ward on resource utilization and outcomes among hospitalized cancer survivors.

36 Background: With improvements in both early detection and cancer treatment, there is a growing population of cancer survivors; with a corresponding increase in acute care use. However, models of inpatient care delivery for cancer survivors differ between hospitals and regions, which may impact resource use and outcomes. Understanding how different models influence outcomes may help define optimal models for cancer inpatient care delivery. Methods: We created a multicenter cohort of all cancer patients admitted to medical wards across 26 hospitals in Ontario, Canada from 2015 to 2022, and deterministically linked population level administrative data including ambulatory oncology data, with each hospital’s patient-level electronic information (pharmacy, orders, notes, labs/imaging and results). Multivariable regression models compared characteristics and outcomes between patients admitted on oncology wards vs non-oncology wards adjusting for age, sex, income quintile, rurality, immigrant status, receiving IV systemic therapy within 120 days and comorbidity scores. Results: In total, there were 370,118 hospitalizations from 191,990 unique patients. Among these hospitalizations, 38,075 episodes (10%) were on an oncology ward. Median time from cancer diagnosis to hospitalization was 4 years; 10% received IV systemic therapy within 120 days and 16% within 1 year. The most common disease sites were GU (21%), GI (20%), breast (12%) and lung (10%). The most common discharge diagnoses from oncology wards were inpatient chemotherapy (9%), febrile neutropenia (7%), NHL (4%), AML (4%), myeloma (3%); while for non-oncology wards were heart failure (5%), palliative care (4%), UTI (2%), pneumonia (2%), acute renal failure (2%). In general, cancer patients admitted on oncology wards were younger (64 vs 76), had shorter length of stay (LOS; 9.6 vs 10.1 days), less in-hospital mortality (8% vs 11%), greater 30-day re-admission rates (30% vs 15%) and were more likely to undergo CTs (28% vs 21%), MRIs (11% vs 9%) and interventional procedures (8% vs 6%) (p<0.001, all). Subgroup analysis focusing on the top 5 discharge diagnoses from non-oncology wards, showed that despite no difference in in-hospital mortality rates (aOR 0.92 95% CI [0.58-1.46] p=0.73), admission to a non-oncology ward for those diagnoses was associated with shorter LOS (aOR 0.84 [0.78-0.90] p<0.001), reduced 30-day re-admission rates (aOR 0.60 [0.48-0.75] p<0.001), and reduced use of CTs (aOR 0.60 [0.49-0.74] p<0.001), MRIs (aOR 0.36 [0.25-0.52] p<0.001), and interventional procedures (aOR 0.43 [0.29-0.64] p<0.001). Conclusions: There are differences in resource use and outcomes for cancer survivors hospitalized on oncology versus non-oncology wards, including for patients with the same discharge diagnosis. To optimize inpatient cancer care delivery for hospitalized cancer survivors, further exploration of care models is needed.

Multicenter Integration of MR Radiomics, Deep Learning, and Clinical Indicators for Predicting Hepatocellular Carcinoma Recurrence After Thermal Ablation.

To develop and validate an innovative predictive model that integrates multisequence magnetic resonance (MR) radiomics, deep learning features, and clinical indicators to accurately predict the recurrence of hepatocellular carcinoma (HCC) after thermal ablation. This retrospective multicenter cohort study enrolled patients who were diagnosed with HCC and treated via thermal ablation. We extracted radiomic features from multisequence 3T MR images, analyzed these images using a 3D convolutional neural network (3D CNN), and incorporated clinical data into the model. Model performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The study included 535 patients from three hospitals, comprising 462 males and 43 females. The RDC model, which stands for the Radiomics-Deep Learning-Clinical data model, demonstrated high predictive accuracy, achieving AUCs of 0.794 in the training set, 0.777 in the validation set, and 0.787 in the test set. Statistical analysis confirmed the model's robustness and the significant contribution of the integrated features to its predictive capabilities. The RDC model effectively predicts HCC recurrence after thermal ablation by synergistically combining advanced imaging analysis and clinical parameters. This study highlights the potential of such integrative approaches to enhance prognostic assessments in HCC patients and offers a promising tool for clinical decision-making.

Early clinical predictors of infected pancreatic necrosis: a multicentre cohort study

BackgroundInfected pancreatic necrosis (IPN) exacerbates complications in patients with acute pancreatitis (AP), increasing mortality rates if not treated promptly. We aimed to evaluate the predictive value of clinical characteristics within...

Examining associations between social vulnerability and maternal morbidity among a multicentre cohort of pregnancies complicated by placenta accreta spectrum disorder in New York City

BackgroundPlacenta accreta spectrum (PAS) disorder is a source of severe obstetric morbidity and mortality worldwide. The objective of this paper was to evaluate the potential relationship between social vulnerability and...

Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma☆

Background & AimsThe combination of atezolizumab and bevacizumab offers a novel approach to immunomodulation, showing efficacy as a primary treatment in advanced hepatocellular carcinoma (HCC). Concerns about graft safety and rejection have limited its exploration in the neoadjuvant setting of liver transplantation (LT).This study investigates the clinical efficacy and the safety profile related to the pre-transplant administration of atezolizumab and bevacizumab for HCC. MethodsProspective assessment of 17 patients with HCC treated with neoadjuvant preoperative atezolizumab and bevacizumab prior to LT for HCC, obtained from December 2020 and December 2023 at seven Western transplant centers. ResultsAmong the 17 patients with HCC included in the study, 16 (94.1%) had a tumor burden outside of Milan Criteria (MC). Neoadjuvant loco-regional therapies along with the administration of atezolizumab plus bevacizumab (median:5 months; discontinued at least 4 weeks prior LT), achieved an ORR 94% (Complete response: 59%), downstaging to within MC (82%) and a pathological response at explant examination of 88%. Grade 3-4 TRAE accounted for 17.6% of cases and were manageable. During the 25 months median follow-up period, 2 cases of mild (RAI ≤ 4), biopsy-proven rejection were reported but no instances of severe allograft rejection or graft loss. The 1-year and 3-year post-LT survival rates were 94.2% and 88.2%, respectively. ConclusionsThis study highlights the favorable oncological and survival outcomes from a multicentric cohort of HCC patients treated with atezolizumab and bevacizumab in the pre-LT setting. This immune-based combination was safe in terms of TRAE, and absence of severe post-transplant rejection or graft loss. These preliminary results could pave the way for expanding transplant eligibility criteria in patients at more advanced HCC stages. Impact and Implications•The combination of atezolizumab and bevacizumab in the neoadjuvant setting prior to liver transplantation for hepatocellular carcinoma (HCC) has been limitedly explored despite its potential to enhance anti-tumor response and downstaging due to raising concerns about its safety profile.•Among 17 patients who underwent successful liver transplantation following neoadjuvant atezolizumab/bevacizumab, 82% achieved downstaging to within MC, 94% radiological objective response and 88% pathology response, without drop-outs due to TRAEs or graft loss.•The neoadjuvant combination of atezolizumab plus bevacizumab prior liver transplantation in HCC shows an encouraging safety profile and stands out as a promising pre-transplant optimization treatment adjunct, leading to improved oncological outcomes

Impact of primary care and public health integration of chronic conditions in China: a protocol for a prospective multicentre cohort study

IntroductionThe prevalence of chronic conditions is increasing. Given that the majority of chronic patients are managed by primary healthcare providers, there is a need to integrate primary care with public...

Pregnancy loss in individuals with von Willebrand disease and unspecified mucocutaneous bleeding disorders: A multicentre cohort study

BackgroundWhile bleeding around pregnancy is well described in von Willebrand disease (VWD), risk of pregnancy loss is less certain. We aimed to describe the frequency of pregnancy loss in females with VWD, compared with those with a similar mucocutaneous bleeding phenotype and no VWD, or compared with non-bleeding disorder controls. MethodsFemale patients were consecutively approached in 8 specialty bleeding disorder clinics between 2014-2023. The VWD group was defined as having VWF:Antigen (Ag) and VWF:Activity (Act) levels, each <0.50 IU/mL on ≥2 occasions, and a Condensed MCMDM-1 score of ≥4. The non-VWD mucocutaneous bleeding disorder group had VWF levels ≥0.50 IU/mL on ≥2 occasions and a MCMDM-1 score ≥4. A non-bleeding disorder control group was recruited in pregnancy from a low-risk maternity clinic. ResultsThere were 150 females in the VWD group, 145 in the non-VWD mucocutaneous bleeding disorder group, and 137 in the control group. There was a similar frequency of individuals with ≥1 loss in the VWD group (45.3%, 68/150), the non-VWD group (56.6%, 82/145) (-11.2%, 97.5% CI -24.2, 1.8%), and the non-bleeding disorder control group (37.2%, 51/137) (8.1%, 97.5% CI -4.9%, 21.1%). Using a logistic regression, the odds ratio of pregnancy losses in the VWD group versus non-VWD group was 0.94 (95% CI 0.65, 1.36). All groups experienced more recurrent losses compared to the literature. ConclusionsThere was no statistically significant difference in risk of pregnancy loss between females with VWD, females with a similar mucocutaneous bleeding phenotype, and with non-bleeding disorder controls.

241P Long term follow-up of CHRNE congenital myasthenic syndrome (CMS) – a retrospective multi-centre cohort study

241P Long term follow-up of CHRNE congenital myasthenic syndrome (CMS) – a retrospective multi-centre cohort study

Predicting frailty domain impairments and mortality with the Hospital Frailty Risk Score among older adults with cancer: the ELCAPA-EDS cohort study.

Automated frailty screening tools like the Hospital Frailty Risk Score (HFRS) are primarily validated for care consumption outcomes. We assessed the predictive ability of the HFRS regarding care consumption outcomes, frailty domain impairments and mortality among older adults with cancer, using the Geriatric 8 (G8) screening tool as a clinical benchmark. This retrospective, linkage-based study included patients aged ≥70years with solid tumor, enrolled in the Elderly Cancer Patients (ELCAPA) multicentre cohort study (2016-2020) and hospitalized in acute care within the Greater Paris University Hospitals. HFRS scores, which encompass hospital-acquired problems and frailty-related syndromes, were calculated using data from the index admission and the preceding 6months. A multidomain geriatric assessment (GA), including cognition, nutrition, mood, functional status, mobility, comorbidities, polypharmacy, incontinence, and social environment, was conducted at ELCAPA inclusion, with computation of the G8 score. Logistic and Cox regressions measured associations between the G8, HFRS, altered GA domains, length of stay exceeding 10days, 30-day readmission, and mortality. Among 587 patients included (median age 82years, metastatic cancer 47.0%), 237 (40.4%) were at increased frailty risk by the HFRS (HFRS>5) and 261 (47.5%) by the G8 (G8≤10). Both HFRS and G8 were significantly associated with cognitive and functional impairments, incontinence, comorbidities, prolonged length of stay, and 30-day mortality. The G8 was associated with polypharmacy, nutritional and mood impairment. Although showing significant associations with short-term care consumption, the HFRS could not identify polypharmacy, nutritional, mood and social environment impairments and showed low discriminatory ability across all GA domains.

Evaluating optimal rehabilitation strategies in ICU: study protocol for a multicentre cohort study to assess Physical Activity dosing, Muscle mass, and physICal outcomeS (IPAMICS study)

Evaluating optimal rehabilitation strategies in ICU: study protocol for a multicentre cohort study to assess Physical Activity dosing, Muscle mass, and physICal outcomeS (IPAMICS study)

Association of HRS-AKI with Mortality in Patients with Cirrhosis Requiring Renal Replacement Therapy: Results from the HRS-HARMONY Consortium.

While AKI requiring renal replacement therapy (AKI-RRT) is associated with increased mortality in heterogeneous inpatient populations, the epidemiology of AKI-RRT in hospitalized patients with cirrhosis is not fully known. Herein, we evaluated the association of etiology of AKI with mortality in hospitalized patients with cirrhosis and AKI-RRT in a multicentric contemporary cohort. This is a multicenter retrospective cohort study using data from the HRS-HARMONY consortium, which included 11 U.S. hospital network systems. Consecutive adult patients admitted in 2019 with cirrhosis and AKI-RRT were included. The primary outcome was 90-day mortality, and the main independent variable was AKI etiology, classified as hepatorenal syndrome (HRS-AKI) vs. other (non-HRS-AKI). AKI etiology was determined by at least two independent adjudicators. We performed Fine and Gray sub-distribution hazard analyses adjusting for relevant clinical variables. Of 2,063 hospitalized patients with cirrhosis and AKI, 374 (18.1%) had AKI-RRT. Among these, 65 (17.4%) had HRS-AKI and 309 (82.6%) non-HRS-AKI, which included ATN in most cases (62.6%). Continuous RRT (CRRT) was used as the initial modality in 264 (71%) of patients, while intermittent hemodialysis (IHD) was utilized in 108 (29%). The HRS-AKI (vs. non-HRS-AKI) group received more vasoconstrictors for HRS management (81.5% vs. 67.9%), while the non-HRS-AKI group received more mechanical ventilation (64.3% vs. 50.8%) and more CRRT (vs. IHD) as the initial RRT modality (73.9% vs. 56.9%). In the adjusted model, HRS-AKI (vs. non-HRS-AKI) was not independently associated with increased 90-day mortality (sHR=1.36, 95% CI: 0.95-1.94). In this multicenter contemporary cohort of hospitalized adult patients with cirrhosis and AKI-RRT, HRS-AKI was not independently associated with an increased risk of 90-day mortality when compared to other AKI etiologies. The etiology of AKI appears less relevant than previously considered when evaluating the prognosis of hospitalized adult patients with cirrhosis and AKI requiring RRT.

Establishment of a survival predictive model for patients with two synchronous multiple primary lung cancers: a multicenter cohort analysis.

The prognostic predictors of the synchronous multiple primary lung cancer (SMPLC) still remain unclear, and there is a lack of studies on the prognosis of SMPLC patients excluding those with multifocal ground-glass/lepidic (GG/L) nodules. The aim of this study is to develop an effective model for predicting survival of SMPLC patients. In this multicenter cohort study, a total of 831 SMPLC patients presenting for lung cancer resection from January 2004 to January 2018 at five institutions were included for developing and validating a nomogram model. Specifically, 499 patients from the Cancer Hospital, Chinese Academy of Medical Sciences, and Beijing Chao-Yang Hospital, Capital Medical University were served as the training cohort. A total of 332 patients from The Third Xiangya Hospital of Central South University, the First Affiliated Hospital of University of Science and Technology of China, and Beijing Liangxiang Hospital were served as the external validation cohort. The nomogram model was compared with the Tumor Node Metastasis (TNM) system for the overall survival. The C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the model performance. A user-friendly website for SMPLC survival probability calculation was also provided for a better understanding of prognosis of patients with resected SMPLC. A total of seven independent risk factors were selected by conducting a multivariate analysis on the training set. Further, a nomogram model was developed with these factors. Both the internal and external validations exhibited good discrimination (C-index: internal, 0.827; external, 0.784). The NRI and IDI of this model were 0.33 and 0.21, respectively. The survival rates for 1-year, 3-year, and 5-year were consistent with the actual observed values. A set of cutoff values were determined by grouping the patients into three different groups. For each group, we should expect a significant distinction between survival curves. The novel nomogram model enables accurate survival risk stratification of patients with resected SMPLC and may assist in decision-making that is conducive to patients with SMPLC at high risk.

Association Between Admission Systolic Blood Pressure and Outcomes in Patients with Isolated Traumatic Brain Injury: A Cross-National Multicenter Cohort Study.

The optimal prehospital blood pressure in patients following traumatic brain injury (TBI) remains controversial. We aimed to assess the association between the systolic blood pressure (SBP) at emergency department triage and patient outcomes following isolated moderate-to-severe TBI. We conducted a cross-national multicenter retrospective cohort study using the Pan-Asia Trauma Outcomes Study database from January 1, 2016, to November 30, 2018. The enrollees were adult patients with isolated moderate-to-severe TBI defined by the International Classification of Diseases code, a Glasgow Coma Scale (GCS) <13 at triage, and a nonhead Abbreviated Injury Scale ≤3. The studied variables were SBPs at triage categorized into different ranges. The primary outcome was 30-day mortality, and the secondary outcome was poor functional status at hospital discharge defined by the modified Rankin Scale ≥4. Multivariable logistic regression was applied to adjust for confounders including country, sex, age, mechanism of injury, prehospital vascular access, respiratory rate, GCS, oxygen saturation, intubation, Injury Severity Score, head surgery, intensive care unit admission, and length of hospital stay. Subgroup analyses were performed on different severity of TBI. A total of 785 patients (median age, 42 years; male patients 77.5%; mean SBP at triage, 136.3 ± 33.1 mmHg) were included in the primary analysis. The lowest 30-day mortality rate existed in patients with SBP of 100-119 mmHg. Taking it as baseline, the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of SBP <100 mmHg, 120-139 mmHg, 140-159 mmHg, and ≥160 mmHg were 7.05 (2.51-19.78), 3.14 (1.14-8.65), 2.91 (1.04-8.17), and 3.28 (1.14-9.42). As for the secondary outcome, the aORs and 95% CIs were 1.36 (0.68-2.68) of <100 mmHg, 0.99 (0.57-1.70) of 120-139 mmHg, 1.23 (0.67-2.25) of 140-159 mmHg, and 1.52 (0.78-2.95) of ≥160 mmHg. Subgroup analyses revealed trends of the best outcomes in both moderate and severe TBI patients with SBP 100-119 mmHg, whereas statistical significance appeared only in patients with severe TBI. SBP of 110-119 mmHg at triage is associated with the lowest 30-day mortality in patients following isolated moderate-to-severe TBI and possibly related to a better functional outcome.

Thrombectomy Alone or Alongside Intravenous Thrombolysis in Managing Acute Ischemic Stroke Caused by Basilar Artery Occlusion: A Multicenter Observational Study.

It remains unclear whether the combination of endovascular treatment (EVT) with intravenous thrombolysis (IVT) results in a more favorable functional outcome than EVT alone in managing cases of acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO). Thus, this study aimed to compare the outcomes of two approaches-direct EVT (DEVT) and bridging therapy (IVT plus EVT)-in acute BAO patients presenting within 4.5 hours of stroke onset. This multicenter retrospective cohort study included 153 acute BAO patients presenting within 4.5 hours of stroke onset. Of these patients, 65 (42.5%) and 88 (57.5%) underwent DEVT and bridging therapy, respectively. The primary outcome was defined as good functional outcome (modified Rankin Scale, 0-3) at 90 days. Additionally, pre-operative clinical features, thrombectomy attempts, successful reperfusion rates, incidences of symptomatic intracranial hemorrhage (sICH), and mortality were compared between the two groups. At 90 days, the rate of good functional outcome was comparable between the DEVT (44.6%) and bridging-therapy (39.8%) groups (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 0.55-2.31; p = 0.753). The bridging-therapy group exhibited a lower percentage of patients requiring ≥ 3 attempts of stent retrieval (aOR, 0.39; 95% CI, 0.16-0.93; p = 0.034). Pre-operative clinical features, rate of successful reperfusion, sICH, and mortality were similar between the two groups. In patients with BAO-induced AIS, DEVT demonstrates a comparable functional outcome to bridging therapy within 4.5 hours of symptom onset, but IVT reduces the number of thrombectomy attempts. AIS, acute ischemic stroke; LVO, large-vessel occlusion; EVT, endovascular treatment; IVT, intravenous thrombolysis; BAO, basilar artery occlusion; DEVT, direct endovascular treatment; sICH, symptomatic intracranial hemorrhage; RCT, randomized controlled trial; IRIS, Improving Reperfusion Strategies in Ischemic Stroke; TOAST, Trial of ORG 10172 in Acute Stroke Treatment; mTICI, modified thrombolysis in cerebral infarction; SD, standard deviation; IQR, interquartile range; ICAS, intracranial atherosclerotic stenosis.

Multicenter retrospective cohort study demonstrates superior safety profile of indobufen over aspirin for Post-CABG antiplatelet therapy.

Coronary artery bypass grafting (CABG) is essential for treating coronary artery disease, with postoperative aspirin crucial to prevent graft restenosis. However, its gastrointestinal side effects may limit tolerability in some patients. Indobufen presents a potential alternative, but its safety and efficacy need further validation. This study aimed to compare the efficacy and safety of indobufen versus aspirin in patients' post-CABG. This retrospective observational study included 39 patients who underwent CABG at two centers from January to December 2023. Patients were retrospectively assigned to two groups based on the antiplatelet therapy they received: the indobufen group (n = 19) and the aspirin group (n = 20). The primary endpoint was a composite of non-fatal myocardial infarction, stroke, and revascularization due to acute coronary syndrome in the intention-to-treat population. Postoperative data on platelet count, hemoglobin, D-dimer, activated partial thromboplastin time (APTT), and hospital stay length were collected. Transfusion rate, bleeding, thrombotic events, and gastrointestinal adverse reactions were compared between the two groups. Over the 8-to-18-month follow-up period, 5 patients (25%) in the aspirin group reached the primary endpoint, while none in the indobufen group did, a difference that was statistically significant (p = 0.02). Although the rates of non-fatal myocardial infarction, revascularization, stroke, and thrombotic events were higher in the aspirin group, these differences did not reach statistical significance. Importantly, the total bleeding events were markedly lower in the indobufen group (15.79% vs. 55%, p = 0.011), with major bleeding events also significantly reduced in the indobufen group (0% vs. 20%, p = 0.04). Both groups showed no significant differences were observed in postoperative hospital stay, hemoglobin, and D-dimer levels between the groups. However, the indobufen group demonstrated significantly lower platelet count and APTT. The average daily cost of indobufen was 27.8 times higher than that of aspirin. Indobufen demonstrates a comparable antiplatelet effect to aspirin and offers significant advantages in reducing gastrointestinal adverse reactions and bleeding risk. It can be considered a preferable alternative for patients who cannot tolerate or have contraindications to aspirin. Further large-scale clinical trials are needed to confirm its potential as the first-choice antiplatelet therapy post-CABG.

Structural and functional brain markers of cognitive impairment in healthcare workers following mild SARS-CoV-2 infection during the original stream.

Severe acute respiratory syndrome coronavirus 2 infection often involves the nervous system, leading to cognitive dysfunctions, fatigue and many other neurological signs that are becoming increasingly recognized. Despite mild forms of the disease accounting for most cases worldwide, research on the pathophysiology driving mild coronavirus disease 2019 (COVID-19) has received little attention. In this respect, recent evidence has pointed out that around 30-40% of non-critical, mild-to-moderate severity COVID-19 survivors may display cognitive disturbances several months post-illness. Hence, the impact of COVID-19 on the brain structure and function, through potential neuropathological mechanisms underpinning cognitive alterations in post-mild COVID-19 infections, remains largely unexplored. This retrospective multicentre observational cohort study, entirely based on a healthcare worker sample (n = 65; 55% females, aged 21-61), investigated the cognitive status and the structural and functional brain integrity among non-hospitalized individuals who developed mild COVID-19 symptoms during the occurrence of severe acute respiratory syndrome coronavirus 2 variants Alpha to Delta, compared with healthy controls tested before the pandemic onset. All evaluations were performed at an average of 9-month follow-up post-infection period. Participants completed a comprehensive neuropsychological assessment and structural and functional MRI exams. Radiological inspection sought to detect the presence of white matter hyperintensities on axial fluid-attenuated inversion recovery images. Global and regional grey matter integrity assessment, analysing changes in grey matter volumes and cortical thinning, and functional connectivity alterations of resting-state brain networks were also conducted. Regression analyses tested the relationships between the presence of specific cognitive impairments and potential structural and functional brain findings. Our results revealed that clinical, cognitive screening and neuropsychological examinations were average between both groups, except for specific impairments related to executive functions in the mild COVID-19. Compared to healthy controls, mild COVID-19 subjects exhibited increased juxtacortical white matter hyperintensities, thalamic and occipital volume loss and diminished resting-state functional connectivity involving the left precuneus and cuneus in default-mode network and affecting the right angular gyrus and left precuneus in the dorsal attentional network. Reduced thalamic volume was the only variable selected in the final model explaining the observed executive function impairment in mild COVID-19. The presence of cognitive, structural and functional brain abnormalities over time suggests that the action of widespread neurovascular and inflammatory phenomena on the nervous system might also occur in mild forms following COVID-19 infection rather than permanent brain damage linked to the direct or indirect action of the virus. Our findings emphasize the need to pay attention to the long-term brain-related consequences of mild COVID-19 infections during the original stream.

N-terminal pro-B-type natriuretic peptide, eGFR, and progression of kidney disease in chronic kidney disease patients without heart failure.

Cardiorenal syndrome highlights the bidirectional relationship between kidney and heart dysfunction. N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is the gold standard biomarker in heart failure (HF), may be an important biomarker for chronic kidney disease (CKD) progression. However, NT-proBNP is negatively related with estimated glomerular filtration rate (eGFR). In this study, we investigated the association of NT-proBNP, eGFR, and progression of kidney disease in CKD patients without HF. This multicentric retrospective cohort study recruited 23 860 CKD patients without HF, who had at least one NT-proBNP record from China Renal Data System database. Linear regression model evaluated the relationship between eGFR and NT-proBNP. Cox regression analysis assessed the association between NT-proBNP and CKD progression. Sensitivity analysis examined the robustness of the main findings. This study involved 23 860 CKD patients without HF, distributed across different CKD stages: 10 526 in stages G1-2, 4665 in G3a, 3702 in G3b, 2704 in G4, and 2263 in G5. NT-proBNP was negatively correlated with eGFR, particularly in stages 4-5 CKD. A 15-unit decrease in eGFR was associated with increases in log (NT-proBNP) levels by 1.04-fold, 1.27-fold, 1.29-fold, 1.80-fold, and 3.50-fold for stages 1-2, 3a, 3b, 4, and 5, respectively. After excluding patients who developed CKD progression within 1 year, the Cox regression analysis revealed that the relationship between NT-proBNP and CKD progression was not significant in stages 4 and 5. However, for stages 1-3, each standard deviation increase in log (NT-proBNP) was associated with a 26%, 36%, and 28% higher risk of CKD progression, with P interaction ≤.001. The hazard ratios were 1.26 (95% confidence intervals (CI), 1.18 to 1.35), 1.36 (95% CI, 1.22 to 1.51), and 1.28 (95% CI, 1.14 to 1.43) for stages 1-2, stage 3a, and stage 3b, respectively. Despite its strong inverse association with eGFR, NT-proBNP was positively associated with the risk of progression of kidney disease in CKD patients with stages 1-3 without HF. Future studies should investigate the effectiveness of NT-proBNP as a predictive biomarker for the progression of kidney disease across diverse racial groups and healthcare settings.

70-Gene signature-guided adjuvant systemic treatment adjustments in early-stage ER+ breast cancer patients: 7-year follow-up of a prospective multicenter cohort study.

A previous prospective multicenter study revealed the change of the oncologists' chemotherapy advice due to the 70-Gene signature (GS) test result in half of the estrogen receptor-positive (ER+) invasive early-stage breast cancer patients with disputable chemotherapy indication. This resulted in less patients receiving chemotherapy. This study aims to complement these results by the 7-year oncological outcomes according to the 70-GS test result and the oncologists' pre-test advice. Patients operated for early-stage ER+ breast cancer with disputable chemotherapy indication, had been prospectively included between 2013 and 2015. Oncologists were asked whether they intended to administer adjuvant chemotherapy before deployment of the 70-GS test. Information on adjuvant systemic treatment and oncological outcome was obtained through active follow-up by data managers of the Netherlands Cancer Registry. The primary endpoint of this study was distant metastasis-free survival (DMFS) according to the genomic risk. Exploratory analyses were done to evaluate DMFS in relation to the oncologists' pre-test advice. After a median follow-up of 7 years, distant metastases were diagnosed in 23 of the 606 patients (3.8%) and 36 (5.9%) patients had died. The DMFS rate for the 357 70-GS genomic low-risk patients was 94.2% (95% CI 91.2-96.2) and 89.1% for the 249 genomic high-risk patients (95% CI 84.3-92.4). Of the low-risk patients 3% had received chemotherapy compared to 80% of the high-risk patients. For the subgroups based on the pre-test oncologists' advice (no chemotherapy/chemotherapy/unsure) there were no clinically relevant differences in DMFS (89.8, 93.2 and 92.0%, respectively), while comparable proportions of patients had received chemotherapy. In patients with early-stage ER+ breast cancer with a disputable chemotherapy indication it is sensible to deploy the 70-GS to better select patients for adjuvant chemotherapy.