Novel Plasma Biomarker-Based Model for Predicting Acute Kidney Injury After Cardiac Surgery: A Case Control Study

Introduction:Acute kidney injury (AKI) after cardiac surgery is independently associated with a prolonged hospital stay, increased cost of care, and increased post-operative mortality. Delayed elevation of serum creatinine (SCr) levels requires novel biomarkers to provide a prediction of AKI after cardiac surgery. Our objective was to find a novel blood biomarkers combination to construct a model for predicting AKI after cardiac surgery and risk stratification.Methods:This was a case-control study. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to Gene Expression Omnibus (GEO) dataset GSE30718 to seek potential biomarkers associated with AKI. We measured biomarker levels in venous blood samples of 67 patients with AKI after cardiac surgery and 59 control patients in two cohorts. Clinical data were collected. We developed a multi-biomarker model for predicting cardiac-surgery-associated AKI and compared it with a traditional clinical-factor-based model.Results:From bioinformatics analysis and previous articles, we found 6 potential plasma biomarkers for the prediction of AKI. Among them, 3 biomarkers, such as growth differentiation factor 15 (GDF15), soluble suppression of tumorigenicity 2 (ST2, IL1RL1), and soluble urokinase plasminogen activator receptor (uPAR) were found to have prediction ability for AKI (area under the curve [AUC] > 0.6) in patients undergoing cardiac surgery. They were then incorporated into a multi-biomarker model for predicting AKI (C-statistic: 0.84, Brier 0.15) which outperformed the traditional clinical-factor-based model (C-statistic: 0.73, Brier 0.16).Conclusion:Our research validated a promising plasma multi-biomarker model for predicting AKI after cardiac surgery.

A Combined-Radiomics Approach of CT Images to Predict Response to Anti-PD-1 Immunotherapy in NSCLC: A Retrospective Multicenter Study

ObjectiveBased on non-contrast-enhanced (NCE)/contrast-enhanced (CE) computed tomography (CT) images, we try to identify a combined-radiomics model and evaluate its predictive capacity regarding response to anti-PD1 immunotherapy of patients with non-small-cell lung cancer (NSCLC).Methods131 patients with NSCLC undergoing anti-PD1 immunotherapy were retrospectively enrolled from 7 institutions. Using largest lesion (LL) and target lesions (TL) approaches, we performed a radiomics analysis based on pretreatment NCE-CT (NCE-radiomics) and CE-CT images (CE-radiomics), respectively. Meanwhile, a combined-radiomics model based on NCE-CT and CE-CT images was constructed. Finally, we developed their corresponding nomograms incorporating clinical factors. ROC was used to evaluate models’ predictive performance in the training and testing set, and a DeLong test was employed to compare the differences between different models.ResultsFor TL approach, both NCE-radiomics and CE-radiomics performed poorly in predicting response to immunotherapy. For LL approach, NCE-radiomics nomograms and CE-radiomics nomograms incorporating with clinical factor of distant metastasis all showed satisfactory results, reflected by the AUCs in the training (AUC=0.84, 95% CI: 0.75-0.92; AUC=0.77, 95% CI: 0.67-0.87) and test sets (AUC=0.78, 95% CI: 0.64-0.92, AUC=0.73, 95% CI: 0.57-0.88), respectively. Compared with the NCE-radiomics nomograms, the combined-radiomics nomogram showed incremental predictive capacity in the training set (AUC=0.85, 95% CI: 0.77-0.92) and test set (AUC=0.81, 95% CI: 0.67-0.94), respectively, but no statistical difference (P=0.86, P=0.79).ConclusionCompared with radiomics based on single NCE or CE-CT images, the combined-radiomics model has potential advantages to identify patients with NSCLC most likely to benefit from immunotherapy, and may effectively improve more precise and individualized decision support.

A Phase II Multicenter Trial on High-Dose Vitamin D Supplementation for the Correction of Vitamin D Insufficiency in Patients with Breast Cancer Receiving Adjuvant Chemotherapy

Breast cancer (BC) treatments induce vitamin D (VD) insufficiency and bone metabolism changes, resulting in osteoporosis and skeletal morbidity risk. We report the results of a bicentric phase II trial (ClinicalTrials.gov Identifier: NCT04091178) on the safety and efficacy of high-dose oral VD supplementation for VD deficiency correction in 44 patients with early BC treated with adjuvant chemotherapies. Patients received one dose of 100,000 IU 25-OH VD every 3 weeks from day 1 of cycle 1 to day 1 of cycle 5. The primary endpoint was the percentage of patients achieving serum 25-OH VD concentration normalization on day 1 of cycle 6 (D1C6). Secondary endpoints were safety, VD and calcium parameters at baseline and during chemotherapy, and identification of predictive biomarkers of VD normalization on D1C6. On D1C6, 21 patients (47.7%, 95% CI: 33.0–62.8) achieved VD normalization. No VD-related clinical toxicity was reported. However, 13 patients (29.5%) presented asymptomatic grade 1 hypercalciuria, leading to interruption of the high-dose oral VD supplementation in 10, followed by a rapid reduction in serum VD concentration. No baseline clinical factor was predictive of VD normalization on D1C6. This high-dose VD supplementation appears safe and efficient in patients with early BC receiving adjuvant chemotherapy.

Repeatability and Learning Effect in the 6MWT in Preoperative Cancer Patients Undergoing a Prehabilitation Program

Objective the main objective was to assess repeatability and learning effect of the six-minute walk test (6MWT) in a cohort of preoperative cancer patients referred to a prehabilitation program. As a secondary objective we aimed to identify determinants of improvement in the second test. Materials and Methods secondary analysis from a large prospective study on the implementation of a multimodal prehabilitation program in a real-life scenario. Eligible patients were assessed at baseline before starting the prehabilitation program. The 6MWT was conducted according to the American Thoracic Society (ATS)/ European Respiratory Society (ERS) guidelines with two tests being performed under identical conditions separated by 30 minutes. The distance covered (in meters) and the physiological responses (heart rate, oxygen saturation, fatigue and dyspnea) to each test were recorded and compared. Results 170 patients (60.9%) were analyzed. Repeatability of the distance covered with the 6MWT was excellent (ICC = 0.98; 95% CI: 0.92 – 0.99), but a mean increase of +19.5 meters (95% CI: 15.6 - 23.5m; p=<.001) in the second test was found, showing a learning effect with limits of agreement between -31.3 and 70.4m. Coefficient of variation was 4%. No clinical factor was found to be associated with an improvement in the second test. Conclusions the 6MWT showed excellent repeatability in preoperative cancer patients, but a significant learning effect is present. No associated factors with a clinically meaningful improvement in the second test were identified. In light of these findings, two attempts of the 6MWT should be encouraged in this population.

Golden Syrian Hamsters as a Model for Revisiting the Role of Biological Sex Differences in SARS-CoV-2 Infection

There is growing evidence that coronavirus disease 2019 (COVID-19) affects males more severely than females, including compelling evidence indicating that biological sex is an important clinical factor influencing disease pathology and outcomes. In their recent article in mBio , Dhakal et al. find further evidence to support this hypothesis as they interrogate biological sex differences in the pathogenesis and clinical features of COVID-19 in the golden Syrian hamster model.

Radiomics Nomogram Based on Spectral CT Imaging to Diagnose Osteoporosis

Background: Osteoporosis is associated with a decrease of bone mineralized component as well as a increase of bone marrow fat. At present, there are few studies using radiomics nomogram based fat-water material decomposition (MD) images of spectral CT as an evaluation method of osteoporosis. This study aims to establish and validate a radiomics nomogram based the fat-water imaging of spectral CT in diagnosing osteoporosis.Methods: 95 patients who underwent spectral CT included T11-L2 and dual x-ray absorptiometry (DXA) were collected. The patients were divided into two groups according to T-score, normal bone mineral density (BMD) (T≥-1) and abnormally low BMD (T<-1). Radiomic features were selected from fat-water imaging of the spectral CT. Radscore was calculated by summing the selected features weighted by their coefficients. A nomogram combining the radiomics signature and significant clinical variables was built. The ROC curve was performed to evaluate the performance of the model. Finally, we used decision curve analysis (DCA) to evaluate the clinical usefulness of the model.Results: Five radiomic features based on fat-water imaging of spectral CT were constructed to distinguish abnormally low BMD from normal BMD, and its differential performance was high with an area under the curve (AUC) of 0.95 (95% CI, 0.89-1.00) in the training cohort and 0.97 (95% CI, 0.91-1.00) in the test cohort. The radiomics nomogram showed excellent differential ability with AUC of 0.96 (95%CI, 0.91-1.00) in the training cohort and 0.98 (95%CI, 0.93-1.00) in the test cohort, which performed better than the radiomics model and clinics model only. The DCA showed that the radiomics nomogram had a higher benefit in differentiating abnormally low BMD from normal BMD than the clinical model alone.Conclusion: The radiomics nomogram incorporated radiomics features and clinical factor based the fat-water imaging of spectral CT may serve as an efficient tool to identify abnormally low BMD from normal BMD well.

Hyperintense posterior cerebral artery sign in patients with reversible cerebral vasoconstriction syndrome

Background: This study investigated hyperintense vessel signs (HVS) on fluid-attenuated inversion recovery imaging in the P1–2 portions of posterior cerebral arteries (PCAs) as a “hyperintense PCA sign” and HVS of cortical arteries. We retrospectively examined whether these signs would be useful in diagnosing reversible cerebral vasoconstriction syndrome (RCVS) in the acute phase. Methods: Eighty patients with RCVS who underwent initial magnetic resonance imaging (MRI) within 7 days of onset were included in this study. HVS and related clinical factors were examined. Results: On initial MRI of RCVS patients, hyperintense PCA sign and HVS of cortical arteries were seen in 21 cases (26%) and 38 cases (48%), respectively. In patients showing hyperintense PCA sign, vasoconstriction of the A2–3 portion was a significant clinical factor. Conversely, vasoconstriction of the M1 and P1 portions and the presence of white matter hyperintensity on initial and chronic-stage MRI were significantly associated with the presence of HVS in cortical arteries. Conclusion: Because rich collateral flow exists around PCAs, the frequency of hyperintense PCA sign is not high. However, hyperintense PCA sign findings in patients with suspected RCVS offer credible evidence of extreme flow decreases due to vasoconstriction in peripheral PCAs and other arteries associated with the collateral circulation of PCAs. Conversely, HVS in cortical arteries tend to reflect slow antegrade circulation due to vasoconstriction of peripheral vessel and major trunks. Both signs appear useful for auxiliary diagnosis of acute-phase RCVS.

Smoking Modulates Different Secretory Subpopulations Expressing SARS-CoV-2 Entry Genes in the Nasal and Bronchial Airways

Background: SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments has not been fully characterized using matched samples from large cohorts. Results: Gene expression data from 793 nasal and 1,673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking was the only clinical factor significantly and reproducibly associated with VE gene expression. ACE2 and TMPRSS2 expression were higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48+ secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the RNA-seq confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. Conclusions: The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose these genes are not predominantly expressed in cell populations modulated by smoking. Smoking-induced VE gene expression changes in the nose likely has minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.

Optical Navigation-Related Factors Interfering With The Accuracy of Robot-Assisted Surgery

Objective To explore navigation-related factors interfering with accuracy of robot-assisted surgery. Methods We made a measurement model to test the accuracy of the TianJi Robot system when performing the stimulated screw placement procedure. The three-coordinate machine was used to measure the deviation between the actual position and the planned position. We designed corresponding experiments to explore the effects of different navigation-related factors on the screw placement accuracy. The deviations were measured at different distance (ranging from 1.2 m to 2.2 m) between the navigation optical stereo camera and the tracker and each distance was measured 50 times. The distance between the optical camera and the patient tracker was set at 1.4 m and the deviations were measured at different angles between the camera and the robot tracker, each angle was measured more than 25 times. Data was donated with mean and standard deviation. The line charts were employed to describe the changes of deviations over one clinical factor including distance and angle. Results Within the available scope of navigation optical system (1.2 m-2.2 m), the deviation increased with the distance (χ2=479.107, P<0.001). The robotic system accuracy was high and stable (mean deviation 0.332 mm ± 0.067 mm) when the relative angle between the optical camera and the tracker less than 40 degrees. Conclusions Accuracy of robot system was affected by the relative distance and angle between the optical camera and the tracker. When placing and adjusting the optical tracking devices, surgeons should set the relative distance between the optical camera and the patient tracker as 1.4 m- 1.5 m and the relative angle less than 40 degrees.