Detection of dynamic lung hyperinflation using cardiopulmonary exercise testing and respiratory function in patients with stable cardiac disease: a multicenter, cross-sectional study.

BACKGROUND: Many patients with heart disease potentially have comorbid chronic obstructive pulmonary disease (COPD); however, there are not enough opportunities for screening, and the qualitative differentiation of shortness of breath (SOB) has not been well established. We investigated the detection rate of SOB based on a visual and qualitative dynamic lung hyperinflation (DLH) detection index during cardiopulmonary exercise testing (CPET) and assessed potential differences in respiratory function between groups. METHODS: We recruited 534 patients with heart disease or patients who underwent simultaneous CPET and spirometry (369 males, 67.0 ± 12.9 years) to scrutinize physical functions. The difference between inspiratory and expiratory tidal volume was calculated (TV E-I) from the breath-by-breath data. Patients were grouped into convex (decreased TV E-I) and non-convex (unchanged or increased TV E-I) groups based on their TV E-I values after the start of exercise. RESULTS: Among the recruited patients, 129 (24.2%) were categorized in the convex group. There was no difference in clinical characteristics between the two groups. The Borg scale scores at the end of the CPET showed no difference. VE/VCO2 slope, its Y-intercept, and minimum VE/VCO2 showed no significant difference between the groups. In the convex group, FEV1.0/FVC was significantly lower compared to that in the non-convex group (69.4 ± 13.1 vs. 75.0 ± 9.0%). Moreover, significant correlations were observed between FEV1.0/FVC and Y-intercept (r=-0.343), as well as between the difference between minimum VE/VCO2 and VE/VCO2 slope (r=-0.478). CONCLUSIONS: The convex group showed decreased respiratory function, suggesting a potential airway obstruction during exercise. A combined assessment of the TV E-I and Y-intercept of the VE/VCO2 slope or the difference between the minimum VE/VCO2 and VE/VCO2 slopes could potentially detect COPD or airway obstruction.

Trans men can achieve adequate muscular development through low-dose testosterone therapy: A long-term study on body composition changes.

BACKGROUND: Transgender individuals undergo the gender-affirming hormone therapy (GAHT) to achieve physical changes consistent with their gender identity. Few studies are available on the long-term safety and efficacy of GAHT. OBJECTIVES: To investigate the long-term physical effects and the safety of the testosterone therapy for trans men and to assess the impact of differential hormone dose. MATERIALS AND METHODS: Trans men who initiated GAHT between May 2000 and December 2021 were included in this retrospective analysis. Physical findings (body mass index, body fat percentage (BFP), lean body mass (LBM), and grip strength), blood testing results (hemoglobin, hematocrit, uric acid, creatinine, total cholesterol, triglycerides, and total testosterone), and menstrual cessation were recorded. We assessed the effects of testosterone on body composition changes and laboratory parameters, comparing a low-dose group (≤ 62.5 mg/wk) to a high-dose group (> 62.5 mg/wk). RESULTS: Of 291 participants, 188 patients (64.6%) were in the low-dose group and 103 (35.4%) in the high-dose group. Cumulative menstrual cessation rates up to 12 months were not significantly different between groups. Both groups showed a decrease in BFP and an increase in LBM during the first year of therapy, followed by a slight increase in both over the long term. The high-dose group exhibited greater LBM gains during the first year. Higher hormone doses and lower initial LBM values were associated with LBM increases at 3 and 6 months (3 mo, P = 0.006, P < 0.001; 6 mo, P = 0.015, P < 0.001). There were no long-term, dose-dependent side effects such as polycythemia or dyslipidemia. CONCLUSION: Long-term GAHT for trans men is safe and effective. Low-dose testosterone administration is sufficient to increase LBM in trans men. Higher testosterone doses can lead to an earlier increase in muscle mass.

Impact of Hemoglobin Level in Ex Vivo Heart Perfusion on Donation After Circulatory Death Hearts: A Juvenile Porcine Experimental Model.

BACKGROUND: Ex vivo heart perfusion (EVHP) of donation after circulatory death (DCD) hearts has become an effective strategy in adults; however, the small circulating volume in pediatrics poses the challenge of a low-hemoglobin (Hb) perfusate. We aimed to determine the impact of perfusate Hb levels during EVHP on DCD hearts using a juvenile porcine model. METHODS: Sixteen DCD piglet hearts (11-14 kg) were reperfused for 4 h in unloaded mode followed by working mode. Metabolism, cardiac function, and cell damage were compared between the low-Hb (Hb, 5.0-5.9 g/dL; n = 8) and control (Hb, 7.5-8.4 g/dL; n = 8) groups. Between-group differences were evaluated using 2-sample t-tests or Fisher's Exact tests. RESULTS: During unloaded mode, the low-Hb group showed lower myocardial oxygen consumption (P < 0.001), a higher arterial lactate level (P = 0.001), and worse systolic ventricular function (P < 0.001). During working mode, the low-Hb group had a lower cardiac output (mean, 71% versus 106% of normal cardiac output, P = 0.010) and a higher arterial lactate level (P = 0.031). Adjusted cardiac troponin-I (P = 0.112) did not differ between the groups. Morphological myocyte injury in the left ventricle was more severe in the low-Hb group (P = 0.028). CONCLUSIONS: Low-Hb perfusate with inadequate oxygen delivery induced anaerobic metabolism, resulting in suboptimal DCD heart recovery and declined cardiac function. Arranging an optimal perfusate is crucial to organ protection, and further endeavors to refine the priming volume of EVHP or the transfusion strategy are required.

Determination of enzalutamide long-term safety and efficacy for castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy: a multicenter prospective DELC study.

BACKGROUND: Alternative anti-androgen therapy has been widely used as a first-line treatment for castration-resistant prostate cancer, and it may affect treatment outcome of subsequent agents targeting the androgen receptor axis. We conducted the prospective observational DELC (Determination of Enzalutamide Long-term safety and efficacy for Castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy) study to evaluate the efficacy of enzalutamide in patients with castration-resistant prostate cancer who underwent prior combined androgen blockade with bicalutamide and then alternative anti-androgen therapy with flutamide. METHODS: The DELC study enrolled 163 Japanese patients with castration-resistant prostate cancer who underwent alternative anti-androgen therapy with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients. RESULTS: The rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum levels of prostate-specific antigen (≥11.3 ng/mL; P = 0.004), neuron-specific enolase (P = 0.014) and interleukin-6 (≥2.15 pg/mL; P = 0.004) were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%) and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70. CONCLUSIONS: In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.

Current status and future perspectives on robot-assisted kidney autotransplantation: A literature review.

This review presents the latest insights on robot-assisted kidney autotransplantation (RAKAT). RAKAT is a minimally invasive surgical procedure and represents a promising alternative to conventional laparoscopic nephrectomy followed by open kidney transplantation for the treatment of various complex urological and vascular conditions. RAKAT can be performed either extracorporeally or intracorporeally. Additionally, a single-port approach can be performed through one small incision without the need to reposition the patient. Of 86 patients undergoing RAKAT, 8 (9.3%) developed postoperative > Grade 2 Clavien-Dindo (CD) complications. Although the feasibility of RAKAT was established in 2014, the long-term efficacy and safety along with outcomes of this surgical approach are still being evaluated, and additional studies are needed. With improvements in the technology of RAKAT and as surgeons gain more experience, RAKAT should become increasingly used and further refined, thereby leading to improved surgical outcomes and improved patients' quality of life.

Staged repair for complete atrioventricular septal defect in patients weighing less than 4.0 kg.

OBJECTIVE: This study compared the mortality, left atrioventricular valve-related reoperation, and left atrioventricular valve competence in symptomatic neonates and small infants who underwent staged repair incorporating pulmonary artery banding or primary repair for complete atrioventricular septal defect. METHODS: Patients weighing less than 4.0 kg at the time of undergoing staged (n = 37) or primary (n = 23) repair for balanced complete atrioventricular septal defect between 1999 and 2022 were reviewed. The mean follow-up period was 9.1 years. Freedom from moderate or greater left atrioventricular valve regurgitation was estimated with the Kaplan-Meier method. RESULTS: The staged group included smaller children (median weight, 2.9 vs 3.7 kg) and a higher proportion of neonates (41% vs 4%). All patients in the staged group survived pulmonary artery banding and underwent intracardiac repair (median weight, 6.8 kg). After pulmonary artery banding, the severity of left atrioventricular valve regurgitation improved in 10 of 12 patients (83%) without left atrioventricular valve anomaly who had mild or greater left atrioventricular valve regurgitation and a left atrioventricular valve Z score greater than 0. Although survival and freedom from left atrioventricular valve-related reoperation at 15 years (P = .195 and .602, respectively) were comparable between the groups, freedom from moderate or greater left atrioventricular valve regurgitation at 15 years was higher in the staged group (P = .026). CONCLUSIONS: Compared with primary repair, staged repair for complete atrioventricular septal defect in children weighing less than 4.0 kg resulted in comparable survival and reoperation rates and better left atrioventricular valve competence. Pulmonary artery banding may mitigate secondary left atrioventricular valve regurgitation unless a structural valve abnormality exists. Selective deferred intracardiac repair beyond the neonatal and small-infancy period may still play an important role in low-weight patients.

Prognostic impact of radiological tumor burden in patients with metastatic urothelial carcinoma treated with pembrolizumab.

PURPOSE: Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC. METHODS: We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab. Radiological tumor burden was represented by baseline tumor size (BTS) and baseline tumor number (BTN). Optimal cut-off value of BTS was determined as 50 mm using the Youden index (small BTS: n = 194, large BTS: n = 114). Overall (OS), cancer-specific (CSS), progression-free survival (PFS), and objective response rate (ORR) were compared. Non-linear associations between BTS and OS and CSS were evaluated using restricted cubic splines. RESULTS: Patients with large BTS were less likely to have undergone the surgical resection of the primary tumor (P = 0.01), and more likely to have liver metastasis (P < 0.001) and more metastatic lesions (P < 0.001). On multivariable analyses controlling for the effects of confounders (resection of primary tumor, metastatic site, number of metastases and lactate dehydrogenase level), large BTS and high BTN were independently associated with worse OS (HR 1.52; P = 0.015, and HR 1.69; P = 0.018, respectively) and CSS (HR 1.59; P = 0.01, and HR 1.66; P = 0.031, respectively), but not PFS. Restricted cubic splines revealed BTS was correlated with OS and CSS in linear relationships. Additionally, large BTS was significantly predictive of lower ORR and complete response rate on univariable analyses (P = 0.041 and P = 0.032, respectively), but its association disappeared on multivariable analyses. CONCLUSION: Radiological tumor burden has independent prognostic value with a linear relationship in pembrolizumab-treated patients with mUC and might help drive the earlier introduction of second-line pembrolizumab and/or switching to subsequent therapies.

Discontinuation of Immune-oncology Combinations due to Immune-related Adverse Events in Patients With Advanced Renal Cancers.

BACKGROUND/AIM: Patients with advanced renal cell carcinoma (aRCC) treated with immune-oncology (IO) drugs may need to discontinue the treatment when severe immune-related adverse events (irAE) occur; however, the impact of discontinuation on survival remains unknown. PATIENTS AND METHODS: This is a retrospective multicenter analysis using a database of 183 aRCC patients treated with first-line IO drugs combination. The patients were divided into two groups according to the necessity of discontinuation due to irAEs. The primary endpoint was overall survival (OS). Cox proportional hazard models determined the predictive factors on OS. RESULTS: Among a total of 135 patients who experienced irAE, 38 patients had to discontinue and 52 continued the treatment while treating irAE. When compared to patients who were able to continue treatment, discontinuation was associated with significantly higher rates of IO-IO doublet use, severe irAE (grade ≥3), steroid use, and the occurrence of immune-related pneumonitis (p=0.03, p<0.001, p<0.001, and p=0.02, respectively). The objective response rates were comparable between the two groups (discontinuation 55.6% vs. no discontinuation 56.0%, p=0.7). On univariate analysis, patients who discontinued had a significantly worse OS when compared to those who continued treatment (p=0.02). On the contrary, on multivariate analysis treatment discontinuation was not associated with poor OS (HR=1.1, p=0.9). CONCLUSION: Treatment discontinuation due to irAE was not associated with poor prognosis in aRCC patients treated with ICI-based combination therapy. Treatment discontinuation may be a reasonable treatment option for well-selected patients, specifically for those who experienced good treatment responses.

The Diagnosis and Treatment Approach for Oligo-Recurrent and Oligo-Progressive Renal Cell Carcinoma.

One-third of renal cell carcinomas (RCCs) without metastases develop metastatic disease after extirpative surgery for the primary tumors. The majority of metastatic RCC cases, along with treated primary lesions, involve limited lesions termed "oligo-recurrent" disease. The role of metastasis-directed therapy (MDT), including stereotactic body radiation therapy (SBRT) and metastasectomy, in the treatment of oligo-recurrent RCC has evolved. Although the surgical resection of all lesions alone can have a curative intent, SBRT is a valuable treatment option, especially for patients concurrently receiving systemic therapy. Contemporary immune checkpoint inhibitor (ICI) combination therapies remain central to the management of metastatic RCC. However, one objective of MDT is to delay the initiation of systemic therapies, thereby sparing patients from potentially unnecessary burdens. Undertaking MDT for cases showing progression under systemic therapies, known as "oligo-progression", can be complex in considering the treatment approach. Its efficacy may be diminished compared to patients with stable disease. SBRT combined with ICI can be a promising treatment for these cases because radiation therapy has been shown to affect the tumor microenvironment and areas beyond the irradiated sites. This may enhance the efficacy of ICIs, although their efficacy has only been demonstrated in clinical trials.

Geriatric nutritional risk index as a prognostic marker of first-line immune checkpoint inhibitor combination therapy in patients with renal cell carcinoma: a retrospective multi-center study.

PURPOSE: This study aimed to investigate the effectiveness of the Geriatric Nutritional Risk Index (GNRI) in predicting the efficacy of first-line immune checkpoint inhibitor (ICI) combination therapy for metastatic or unresectable renal cell carcinoma (RCC) and associated patient prognosis. METHODS: A retrospective study was conducted using data from 19 institutions. The GNRI was calculated using body mass index and serum albumin level, and patients were classified into two groups using the GNRI values, with 98 set as the cutoff point. RESULTS: In all, 119 patients with clear cell RCC who received first-line drug therapy with ICIs were analyzed. Patients with GNRI ≥ 98 had significantly better overall survival (OS) (p = 0.008) and cancer-specific survival (CSS) (p = 0.001) rates than those with GNRI < 98; however, progression-free survival (PFS) did not differ significantly. Inverse probability of treatment weighting analysis showed that low GNRI scores were significantly associated with poor OS (p = 0.004) and CSS (p = 0.015). Multivariate analysis showed that the Karnofsky performance status (KPS) score was a better predictor of prognosis (OS; HR 5.17, p < 0.001, CSS; HR 4.82, p = 0.003) than GNRI (OS; HR 0.36, p = 0.066, CSS; HR 0.35, p = 0.072). In a subgroup analysis of patients with a good KPS and GNRI ≥ 98 vs < 98, the 2-year OS rates were 91.4% vs 66.9% (p = 0.068), 2-year CSS rates were 91.4% vs 70.1% (p = 0.073), and PFS rates were 39.7% vs 21.4 (p = 0.27), respectively. CONCLUSION: The prognostic efficiency of GNRI was inferior to that of the KPS score at the initiation of the first-line ICI combination therapy for clear cell RCC.

Quantitative Computed Tomography Analysis of the Longitudinal Change Between Centrilobular and Paraseptal Emphysema Subtypes: A Retrospective Study.

OBJECTIVE: This study aimed to investigate the difference between the extent of centrilobular emphysema (CLE) and paraseptal emphysema (PSE) on follow-up chest CT scans and their relationship to the cross-sectional area (CSA) of small pulmonary vessels. METHODS: Sixty-two patients (36 CLE and 26 PSE) who underwent 2 chest CT scans were enrolled in this study. The percentage of low attenuation volume (%LAV) and total CSA of the small pulmonary vessels <5 mm 2 (%CSA < 5) were measured at the 2 time points. Analysis of the initial %CSA < 5 and the change in the %LAV and %CSA < 5 on follow-up imaging was performed. RESULTS: The initial %CSA < 5 was not significantly different between the CLE and the PSE groups (CLE, 0.66 vs. PSE, 0.71; P = 0.78). There was no significant difference in the longitudinal change in the %LAV between the 2 groups (CLE, -0.048% vs. PSE, 0.005%; P = 0.26). The longitudinal change in the %CSA < 5 in patients with PSE significantly decreased compared with those with CLE (CLE, 0.025% vs. PSE, -0.018%; P = 0.02). CONCLUSIONS: The longitudinal change in the %CSA < 5 was significantly different for patients with CLE and PSE, demonstrating an important pathophysiological difference between the subtypes.

Aberrant phosphorylation of human LRH1 at serine 510 is predictable of hepatocellular carcinoma recurrence.

We previously identified the AKT-phosphorylation sites in nuclear receptors and showed that phosphorylation of S379 in mouse retinoic acid γ and S518 in human estrogen receptor α regulate their activity independently of the ligands. Since this site is conserved at S510 in human liver receptor homolog 1 (hLRH1), we developed a monoclonal antibody (mAb) that recognized the phosphorylation form of hLRH1S510 (hLRH1pS510) and verified its clinicopathological significance in hepatocellular carcinoma (HCC). We generated the anti-hLRH1pS510 mAb and assessed its selectivity. We then evaluated the hLRH1pS510 signals in 157 cases of HCC tissues by immunohistochemistry because LRH1 contributes to the pathogenesis of diverse cancers. The developed mAb specifically recognized hLRH1pS510 and worked for immunohistochemistry of formalin-fixed paraffin-embedded tissues. hLRH1pS510 was exclusively localized in the nucleus of HCC cells, but the signal intensity and positive rates varied among the subjects. According to the semi-quantification, 45 cases (34.9%) showed hLRH1pS510-high, and the remaining 112 cases (65.1%) exhibited hLRH1pS510-low. There were significant differences in the recurrence-free survival (RFS) between the two groups, and the 5-year RFS rates in the hLRH1pS510-high and hLRH1pS510-low groups were 26.5% and 46.1%, respectively. In addition, high hLRH1pS510 was significantly correlated with portal vein invasion, hepatic vein invasion, and high levels of serum alpha-fetoprotein (AFP). Furthermore, multivariable analysis revealed that hLRH1pS510-high was an independent biomarker for HCC recurrence. We conclude that aberrant phosphorylation of hLRH1S510 is a predictor of poor prognosis for HCC. The anti-hLRH1pS510 mAb could provide a powerful tool to validate the relevance of hLRH1pS510 in pathological processes such as tumor development and progression.

Improved Peak Oxygen Uptake Reduces Cardiac Events After 3 Weeks of Inpatient Cardiac Rehabilitation for Chronic Heart Failure Patients.

Background: The incidence of heart failure (HF) is increasing, and the mortality from HF remains high in an aging society. Cardiac rehabilitation (CR) programs (CRP) increase oxygen uptake (V̇O2) and reduce HF rehospitalization and mortality. Therefore, CR is recommended for every HF patient. However, the number of outpatients undergoing CR remains low, with insufficient attendance at CRP sessions. In this study we evaluated the outcomes of 3 weeks of inpatient CRP (3w In-CRP) for HF patients. Methods and Results: This study enrolled 93 HF patients after acute-phase hospitalization between 2019 and 2022. Patients participated in 30 sessions of 3w In-CRP (30 min aerobic exercise twice daily, 5 days/week). Before and after 3w In-CRP, patients underwent a cardiopulmonary exercise test, and cardiovascular (CV) events (mortality, HF rehospitalization, myocardial infarction, and cerebrovascular disease) after discharge were evaluated. After 3w In-CPR, mean (±SD) peak V̇O2 increased from 11.8±3.2 to 13.7±4.1 mL/min/kg (116.5±22.1%). During the follow-up period (357±292 days after discharge), 20 patients were rehospitalized for HF, 1 had a stroke, and 8 died for any reasons. Proportional hazard and Kaplan-Meier analyses demonstrated that CV events were reduced among patients with a 6.1% improvement in peak V̇O2 than in patients without any improvement in peak V̇O2. Conclusions: 3w In-CRP for HF patients improved peak V̇O2 and reduced CV events in HF patients with a 6.1% improvement in peak V̇O2.

Three Weeks of Inpatient Cardiac Rehabilitation Improves Metabolic Exercise Data Combined With Cardiac and Kidney Indexes Scores for Heart Failure With Reduced Ejection Fraction.

Background: Heart failure with reduced ejection fraction (HFrEF) has a high mortality rate, and cardiac rehabilitation programs (CRP) reduce HFrEF rehospitalization and mortality rates. Some countries attempt 3 weeks of inpatient CRP (3w In-CRP) for cardiac diseases. However, whether 3w In-CRP reduces the prognostic parameter of the Metabolic Exercise data combined with Cardiac and Kidney Indexes (MECKI) score is unknown. Therefore, we investigated whether 3w In-CRP improves MECKI scores in patients with HFrEF. Methods and Results: This study enrolled 53 patients with HFrEF who participated in 30 inpatient CRP sessions, consisting of 30 min of aerobic exercise twice daily, 5 days a week for 3 weeks, between 2019 and 2022. Cardiopulmonary exercise tests and transthoracic echocardiography were performed, and blood samples were collected, before and after 3w In-CRP. MECKI scores and cardiovascular (CV) events (heart failure rehospitalization or death) were evaluated. The MECKI score improved from a median 23.34% (interquartile range [IQR] 10.21-53.14%) before 3w In-CRP to 18.66% (IQR 6.54-39.94%; P<0.01) after 3w In-CRP because of improved left ventricular ejection fraction and percentage peak oxygen uptake. Patients' improved MECKI scores corresponded with reduced CV events. However, patients who experienced CV events did not have improved MECKI scores. Conclusions: In this study, 3w In-CRP improved MECKI scores and reduced CV events for patients with HFrEF. However, patients whose MECKI scores did not improve despite 3w In-CRP require careful heart failure management.

Use of machine learning with two-dimensional synthetic mammography for axillary lymph node metastasis prediction in breast cancer: a preliminary study.

Background: As of 2020, breast cancer is the most common type of cancer and the fifth most common cause of cancer-related deaths worldwide. The non-invasive prediction of axillary lymph node (ALN) metastasis using two-dimensional synthetic mammography (SM) generated from digital breast tomosynthesis (DBT) could help mitigate complications related to sentinel lymph node biopsy or dissection. Thus, this study aimed to investigate the possibility of predicting ALN metastasis using radiomic analysis of SM images. Methods: Seventy-seven patients diagnosed with breast cancer using full-field digital mammography (FFDM) and DBT were included in the study. Radiomic features were calculated using segmented mass lesions. The ALN prediction models were constructed based on a logistic regression model. Parameters such as the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: The FFDM model yielded an AUC value of 0.738 [95% confidence interval (CI): 0.608-0.867], with sensitivity, specificity, PPV, and NPV of 0.826, 0.630, 0.488, and 0.894, respectively. The SM model yielded an AUC value of 0.742 (95% CI: 0.613-0.871), with sensitivity, specificity, PPV, and NPV of 0.783, 0.630, 0.474, and 0.871, respectively. No significant differences were observed between the two models. Conclusions: The ALN prediction model using radiomic features extracted from SM images demonstrated the possibility of enhancing the accuracy of diagnostic imaging when utilised together with traditional imaging techniques.

Diamond-like carbon coating to inner surface of polyurethane tube reduces Staphylococcus aureus bacterial adhesion and biofilm formation.

Staphylococcus aureus is one of the main causative bacteria for polyurethane catheter and artificial graft infection. Recently, we developed a unique technique for coating diamond-like carbon (DLC) inside the luminal resin structure of polyurethane tubes. This study aimed to elucidate the infection-preventing effects of diamond-like carbon (DLC) coating on a polyurethane surface against S. aureus. We applied DLC to polyurethane tubes and rolled polyurethane sheets with our newly developed DLC coating technique for resin tubes. The DLC-coated and uncoated polyurethane surfaces were tested in smoothness, hydrophilicity, zeta-potential, and anti-bacterial properties against S. aureus (biofilm formation and bacterial attachment) by contact with bacterial fluids under static and flow conditions. The DLC-coated polyurethane surface was significantly smoother, more hydrophilic, and had a more negative zeta-potential than did the uncoated polyurethane surface. Upon exposure to bacterial fluid under both static and flow conditions, DLC-coated polyurethane exhibited significantly less biofilm formation than uncoated polyurethane, based on absorbance measurements. In addition, the adherence of S. aureus was significantly lower for DLC-coated polyurethane than for uncoated polyurethane under both conditions, based on scanning electron microscopy. These results show that applying DLC coating to the luminal resin of polyurethane tubes may impart antimicrobial effects against S. aureus to implantable medical polyurethane devices, such as vascular grafts and central venous catheters.

High Infiltration of CD163-Positive Macrophages in Intratumor Compartment Predicts Poor Prognosis in Patients With Upper Urinary Tract Urothelial Carcinoma and Radical Nephroureterectomy.

OBJECTIVES: To investigate the prognostic value of CD68- and CD163-positive macrophages in patients with upper urinary tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: This retrospective study enrolled 50 patients (34 men and 16 women) with UTUC who received radical nephroureterectomy (RNU). We evaluated the expression of CD68 and CD163 in the intratumor compartment by immunohistochemistry. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and bladder recurrence-free survival (BRFS). RESULTS: High infiltration of CD163-positive macrophages in patients with UTUC was significantly correlated with worse OS, CSS, and RFS (P < .05 for all). Multivariate analysis showed that high infiltration of CD163-positive macrophages was an independent negative prognostic factor of OS and CSS in patients with UTUC who received RNU. Lymphovascular invasion was an independent negative prognostic factor of RFS, and high infiltration of CD68-positive macrophages was an independent positive prognostic factor of BRFS. CONCLUSION: This study indicated that high infiltration of CD163-positive macrophages in the intratumor compartment might be a useful prognostic marker for survival in patients with UTUC who receive RNU. Further, high infiltration of CD68-positive macrophages in the intratumoral compartment might be a useful prognostic marker for bladder recurrence in these patients.

SPON1 is an independent prognostic biomarker for ovarian cancer.

BACKGROUND: Ovarian cancer has the worst outcome among gynecological malignancies; therefore, biomarkers that could contribute to the early diagnosis and/or prognosis prediction are urgently required. In the present study, we focused on the secreted protein spondin-1 (SPON1) and clarified the prognostic relevance in ovarian cancer. METHODS: We developed a monoclonal antibody (mAb) that selectively recognizes SPON1. Using this specific mAb, we determined the expression of SPON1 protein in the normal ovary, serous tubal intraepithelial carcinoma (STIC), and ovarian cancer tissues, as well as in various normal adult tissues by immunohistochemistry, and verified its clinicopathological significance in ovarian cancer. RESULTS: The normal ovarian tissue was barely positive for SPON1, and no immunoreactive signals were detected in other healthy tissues examined, which was in good agreement with data obtained from gene expression databases. By contrast, upon semi-quantification, 22 of 242 ovarian cancer cases (9.1%) exhibited high SPON1 expression, whereas 64 (26.4%), 87 (36.0%), and 69 (28.5%) cases, which were designated as SPON1-low, possessed the moderate, weak, and negative SPON1 expression, respectively. The STIC tissues also possessed SPON1-positive signals. The 5-year recurrence-free survival (RFS) rate in the SPON1-high group (13.6%) was significantly lower than that in the SPON1-low group (51.2%). In addition, high SPON1 expression was significantly associated with several clinicopathological variables. Multivariable analysis revealed that high SPON1 was an independent prognostic factor for RFS of ovarian cancer. CONCLUSIONS: SPON1 represents a prognostic biomarker for ovarian cancer, and the anti-SPON1 mAb could be valuable as an outcome predictor.

Radiomics model of diffusion-weighted whole-body imaging with background signal suppression (DWIBS) for predicting axillary lymph node status in breast cancer.

BACKGROUND: In breast cancer diagnosis and treatment, non-invasive prediction of axillary lymph node (ALN) metastasis can help avoid complications related to sentinel lymph node biopsy. OBJECTIVE: This study aims to develop and evaluate machine learning models using radiomics features extracted from diffusion-weighted whole-body imaging with background signal suppression (DWIBS) examination for predicting the ALN status. METHODS: A total of 100 patients with histologically proven, invasive, clinically N0 breast cancer who underwent DWIBS examination consisting of short tau inversion recovery (STIR) and DWIBS sequences before surgery were enrolled. Radiomic features were calculated using segmented primary lesions in DWIBS and STIR sequences and were divided into training (n = 75) and test (n = 25) datasets based on the examination date. Using the training dataset, optimal feature selection was performed using the least absolute shrinkage and selection operator algorithm, and the logistic regression model and support vector machine (SVM) classifier model were constructed with DWIBS, STIR, or a combination of DWIBS and STIR sequences to predict ALN status. Receiver operating characteristic curves were used to assess the prediction performance of radiomics models. RESULTS: For the test dataset, the logistic regression model using DWIBS, STIR, and a combination of both sequences yielded an area under the curve (AUC) of 0.765 (95% confidence interval: 0.548-0.982), 0.801 (0.597-1.000), and 0.779 (0.567-0.992), respectively, whereas the SVM classifier model using DWIBS, STIR, and a combination of both sequences yielded an AUC of 0.765 (0.548-0.982), 0.757 (0.538-0.977), and 0.779 (0.567-0.992), respectively. CONCLUSIONS: Use of machine learning models incorporating with the quantitative radiomic features derived from the DWIBS and STIR sequences can potentially predict ALN status.