Propensity score matching as an effective strategy for biomarker cohort design and omics data analysis.

BACKGROUND: Analysis of omics data that contain multidimensional biological and clinical information can be complex and make it difficult to deduce significance of specific biomarker factors. METHODS: We explored the utility of propensity score matching (PSM), a statistical technique for minimizing confounding factors and simplifying the examination of specific factors. We tested two datasets generated from cohorts of colorectal cancer (CRC) patients, one comprised of immunohistochemical analysis of 12 protein markers in 544 CRC tissues and another consisting of RNA-seq profiles of 163 CRC cases. We examined the efficiency of PSM by comparing pre- and post-PSM analytical results. RESULTS: Unlike conventional analysis which typically compares randomized cohorts of cancer and normal tissues, PSM enabled direct comparison between patient characteristics uncovering new prognostic biomarkers. By creating optimally matched groups to minimize confounding effects, our study demonstrates that PSM enables robust extraction of significant biomarkers while requiring fewer cancer cases and smaller overall patient cohorts. CONCLUSION: PSM may emerge as an efficient and cost-effective strategy for multiomic data analysis and clinical trial design for biomarker discovery.

Protein expression of the amino acid transporter SLC7A5 in tumor tissue is prognostic in early-stage colorectal cancer.

Proteins overexpressed in early-stage cancers may serve as early diagnosis and prognosis markers as well as targets for cancer therapies. In this study, we examined the expression of an essential amino acid carrier SLC7A5 (LAT1, CD98, or 4F2 light chain) in cancer tissue from two well-annotated cohorts of 575 cases of early-stage and 106 cases of late-stage colorectal cancer patients. Immunohistochemistry showed SLC7A5 overexpression in 72.0% of early-stage and 56.6% of late-stage cases. SLC7A5 expression was not influenced by patient gender, age, location, or mismatch repair status, although it appeared to be slightly less prevalent in tumors of mucinous differentiation or with lymphovascular invasion. Statistical analyses revealed a positive correlation between SLC7A5 overexpression and both overall survival and disease-free survival in early-stage but not late-stage cancers. Co-expression analyses of the TCGA and CPTAC colorectal cancer cohorts identified a network of gene transcripts positively related to SLC7A5, with its heterodimer partner SLC3A2 having the highest co-expression score. Network analysis uncovered the SLC7A network to be significantly associated with ncRNA such as tRNA processing and the mitotic cell cycle. Since SLC7A5 is also a marker of activated lymphocytes such as NK, T, and B lymphocytes, SLC7A5 overexpression in early colorectal cancers might trigger a strong anti-tumor immune response which could results in better clinical outcome. Overall, our study provides clear evidence of differential SLC7A5 expression and its prognostic value for early-stage colorectal cancer, although the understanding of its functions in colorectal tumorigenesis and cancer immunity is currently rather limited and awaits further characterization.

Correlation Between Intraventricular Pressure Difference and Indexed Flow of a Left Ventricular Assist Device.

OBJECTIVES: There is no definitive parameter for left ventricular (LV) preload in patients with a continuous-flow left ventricular assist device (LVAD). The intraventricular pressure difference (IVPD) is the maximum pressure difference between the mitral valve and LV apex during diastole; and, in past studies, the IVPD was influenced by volume loading. The authors hypothesized that IVPD in LVAD patients correlates with indexed LVAD flow and that IVPD can serve as a novel parameter of LV preload in this population. DESIGN: A single-center, retrospective, observational study. SETTING: A tertiary-care hospital from August 2019 to July 2020. PARTICIPANTS: Sixteen ramp tests for adjustment of LVAD pump speed in 14 adult patients undergoing continuous-flow LVAD implantation. INTERVENTIONS: Measurement of IVPD during ramp tests. MEASUREMENTS AND MAIN RESULTS: LVAD flow and IVPD were measured at each LVAD pump speed during the ramp test for the adjustment of LVAD pump speed after patients came off cardiopulmonary bypass during LVAD implantation. A straight, longitudinal view of the left atrium and left ventricle was obtained, and the pressure difference between the mitral valve and LV apex during diastole was measured by transesophageal echocardiography. The maximum pressure difference during diastole was recorded as IVPD. The relationship between indexed LVAD flow (LVAD flow/body surface area) and IVPD was assessed by a multivariate nonlinear regression analysis with the Huber-White sandwich estimator. IVPD correlated with indexed LVAD flow (p < 0.001). CONCLUSIONS: IVPD is a useful indicator of LV preload during LVAD implantation.

Association between postoperative changes in the gut microbiota and pseudopsia after cardiac surgery: prospective observational study.

BACKGROUND: Delirium after cardiac surgery affects mortality, but the mechanism remains unclear. Previous studies have reported gut microbiota are associated with brain activity. Systemic inflammation and antibiotics can damage the gut microbiota after cardiac surgery. We aimed to investigate changes in the gut microbiota and the association between the gut microbiota and delirium after cardiac surgery. METHODS: Twenty-one patients who underwent cardiac surgery were enrolled. Microbiota counts and fecal organic acid concentrations were measured in fecal samples harvested before surgery, just after surgery, and before discharge. To quantify the microbiota, we extracted total RNA fractions and examined gut microbiota composition using 16S and 23S rRNA-targeted quantitative-reverse Transcription-PCR. Postoperative delirium, insomnia, and pseudopsia were assessed for 1 week. Postoperative total bacterial counts changed significantly from 10.2 ± 0.2 log10 cells/g of feces to 9.8 ± 0.5 in the first postoperative samples (p = 0.003) and 10.0 ± 0.4 in the samples before discharge (p = 0.039). Fecal pH was 6.9 ± 0.6 before surgery and 7.4 ± 0.7 in the first postoperative samples (p = 0.001). Postoperative Staphylococcus and Pseudomonas counts were significantly higher in patients with postoperative pseudopsia than in patients without pseudopsia (3.2 ± 1.3 vs. 5.4 ± 0.9; p = 0.012 and 1.7 ± 0.8 vs. 4.6 ± 2.7; p = 0.001). CONCLUSIONS: Total bacterial counts were significantly lower after surgery and until discharge. Fecal pH was significantly higher than preoperative levels. Staphylococcus and Pseudomonas counts were significantly higher in patients with postoperative pseudopsia.

Simple preoperative computed tomography image analysis shows good predictive performance for pathological vessel invasion in clinical stage IA non-small cell lung cancer.

OBJECTIVES: Pathological vessel invasion is a well-known prognostic factor in early-stage, non-small cell lung cancer and preoperative predicting vessel invasion may enable us to improve prognosis by additional interventions. We evaluated the importance of vessel invasion as a prognostic factor in clinical stage IA non-small cell lung cancer and predictive performance of simple diameter-based computed tomography image analysis for vessel invasion. METHODS: The study design was retrospective, and we reviewed 398 patients who underwent surgical resection of clinical stage IA non-small cell lung cancer from 1999 to 2009. The prognostic factors for recurrence-free survival were examined by univariate and multivariate analyses. Additionally, we analyzed preoperative high-resolution computed tomography images of patients with adenocarcinoma. The greatest diameter of the tumor in the lung window and the length of the consolidation part of L in the mediastinal window were measured. Then the ratio (mediastinal window/lung window) was calculated, and the correlation between the ratio (mediastinal window/lung window) and vessel invasion was analyzed by receiver operating characteristic analysis. RESULTS: Sixty-eight recurrences occurred. Multivariate analysis revealed that vessel invasion, high preoperative serum carcinoembryonic antigen, and history of other malignancy were independent prognostic factors; their hazard ratios were 2.98, 2.45, and 1.98, respectively. The receiver operating characteristic analysis showed that the area under the curve was 0.75. When we set the cut-off value of the ratio (mediastinal window/lung window) at 0.67, the sensitivity and specificity were 75% and 72%, respectively. CONCLUSIONS: Vessel invasion had the greatest impact on recurrence in clinical stage IA non-small cell lung cancer. Our simple computed tomography image analysis showed good predictive performance for vessel invasion.

Osteochondral grafting for treatment of a massive chondral defect in the knee of a young adult with anterior cruciate ligament deficit.

We report the case of a 28-year-old woman who underwent osteochondral grafting and anterior cruciate ligament (ACL) reconstruction for treatment of a massive cartilage defect in a knee joint with ACL deficit. Arthroscopy showed a full-thickness degenerative cartilage defect measuring 22 x 35 mm in the weight-bearing area of the medial femoral condyle, a totally resected lateral meniscus, and a loosened ACL. Therefore we performed osteochondral autograft transplantation and ACL reconstruction. Osteochondral plugs were harvested from a donor site in the patellofemoral joint of the contralateral knee and grafted into the recipient site in a "skipping" manner. Arthroscopic examination 1 year after surgery showed good preservation of the grafts and satisfactory bridging of the gaps between the plugs with fibrocartilage-like tissue. A recent follow-up examination, performed 36 months after surgery, has shown an excellent result, with a Lysholm score of 100, an International Knee Documentation Committee score of 95.4, and full range of knee motion with no symptoms. Plain radiographs at that time showed preservation of the medial joint space on the weighted anteroposterior view. No osteoarthritic changes were evident in the patellofemoral joint.

Icosaniobate: a new member of the isoniobate family.

Icosaniobate [Nb20O54]8- was synthesized by reacting [H4Nb6O19]4- with NO in tetrahydrofuran or MeNO2. A single-crystal X-ray diffraction study of its n-tetrabutylammonium salt [a = 17.7284(18) A, b = 33.542(3) A, c = 34.316(2) A, Z = 4, and space group P22(1)2(1)] revealed a dimeric structure where two decaniobate ions are condensed sharing two terminal O atoms. Unlike that in [(NbW5O18)2O]4-, the Nb-O-Nb bridges in icosaniobate are bent. The nonlinear bridging reduces the maximum possible symmetry of the dimeric anion to mm2, which it closely approximates.