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Recent studies have identified a urinary microbiome, dispelling the myth of urine sterility. Intravesical bacillus Calmette–Guérin (BCG) therapy is the preferred treatment for intermediate to high-risk non-muscle-invasive bladder cancer (BCa), although resistance occurs in 30–50% of cases. Progression to muscle-invasive cancer necessitates radical cystectomy. Our research uses 16S rRNA gene sequencing to investigate how the urinary microbiome influences BCa and its response to BCG therapy. Urine samples were collected via urethral catheterization from patients with benign conditions and non-muscle-invasive BCa, all of whom underwent BCG therapy. We utilized 16S rRNA gene sequencing to analyze the bacterial profiles and metabolic pathways in these samples. These pathways were validated using a real metabolite dataset, and we developed predictive models for malignancy and BCG response. In this study, 87 patients participated, including 29 with benign diseases and 58 with BCa. We noted distinct bacterial compositions between benign and malignant samples, indicating the potential role of the toluene degradation pathway in mitigating BCa development. Responders to BCG had differing microbial compositions and higher quinolone synthesis than non-responders, with two Bifidobacterium species being prevalent among responders, associated with prolonged recurrence-free survival. Additionally, we developed highly accurate predictive models for malignancy and BCG response. Our study delved into the mechanisms behind malignancy and BCG responses by focusing on the urinary microbiome and metabolic pathways. We pinpointed specific beneficial microbes and developed clinical models to predict malignancy and BCG therapy outcomes. These models can track recurrence and facilitate early predictions of treatment responses. [ABSTRACT FROM AUTHOR]

Aqueous zinc (Zn) metal batteries (AZBs) are one of the promising candidates for post-Li-ion batteries for cost-effective and safe large-scale energy storage systems. However, the irreversibility of the Zn metal anode (ZMA) due to Zn dendrite growth and "dead Zn" formation, which is an electrically isolated Zn particle, is a crucial issue for the practical use of AZBs. In response to these drawbacks, a Janus-faced separator composed of an acid-treated carbon supportive layer (aCSL) is proposed, which can perform various functions, rendering additional reaction sites for Zn deposition/dissolution and uniform Zn2+ ion flux owing to excellent wetting by endowed hydrophilicity. By manipulating current density and Zn plating capacity, hydrogen evolution reaction (HER)-dominant and HER-minimized protocols for Zn coulombic efficiency (CE) are proposed for assessing the Zn reversibility. Remarkably, the aCSL exhibits the highest initial CE of each newly suggested protocol, which indicates that the aCSL can suppress the water-induced side reactions and achieved an excellent CE of 99.6% (@ 1 mA cm−2) during 900 cycles and stable symmetric cell performance over 1200 hours (@ 1 mA cm−2). Due to these interesting features, the Zn‖α-MnO2/CNT full cell shows stable cycle performance with capacity retention of 61.3% during 2000 cycles. [ABSTRACT FROM AUTHOR]

Background: Osteochondral lesions of the talus are uncommon in children and adolescents. Surgical procedures differ from those used for adults to avoid iatrogenic physeal injuries. This study aimed to evaluate the clinical and radiological outcomes of surgical treatment in pediatric patients with osteochondral lesions, specifically investigating the patient age and the status of distal tibial physis as factors associated with surgical success. Methods: We retrospectively reviewed 28 patients who had symptomatic osteochondral lesions of the talus that were treated surgically between 2003 and 2016. If the lesion was stable and articular cartilage was intact, retrograde drilling was performed under fluoroscopic guidance. Lesions with detached overlying cartilages were treated by debridement of the cartilage combined with microfracture and drilling. Radiographic outcomes, American Orthopaedic Foot & Ankle Society ankle-hindfoot score, and skeletal maturity were evaluated. Results: Radiological improvement was observed in 24 (24/28, 86%) patients and complete and incomplete healing in 8 and 16 patients, respectively. Changes in pain grades, American Orthopaedic Foot & Ankle Society scores, and radiological healing after surgery were significant (pain grade, p < 0.001; American Orthopaedic Foot & Ankle Society, p = 0.018; radiological healing, p < 0.001). In addition, patients in the younger age group (≤13 years) showed greater improvements in pain grades than older patients (p = 0.02). Improvement in pain grade after surgery was better in the skeletally immature group than in the skeletally mature group (p = 0.048). Conclusion: Clinical and radiological improvements were observed after surgical treatment. The younger age group and open physis group showed more pain improvement. Level of evidence: Therapeutic level IV. [ABSTRACT FROM AUTHOR]

Simple Summary: Renal cell carcinoma (RCC) is a highly vascularized and immunogenic tumor, and its treatment has been revolutionized by the development of immune-checkpoint inhibitors. However, the clinical benefit of these agents is limited in patients with metastatic disease. The microbiome has emerged a novel therapeutic target in recent years and has shown promising values. Understanding the microbiome of the tumor microenvironment is essential for the treatment of RCC. Microbes play different roles in metabolism, local or systemic inflammation, and immunity, and the human microbiome in tumor microenvironment (TME) is important for modulating the response to immunotherapy in cancer patients. Renal cell carcinoma (RCC) is an immunogenic tumor, and immunotherapy is the backbone of its treatment. Correlations between the microbiome and responsiveness to immune checkpoint inhibitors have been reported. This review summarizes the recent therapeutic strategies for RCC and the effects of TME on the systemic therapy of RCC. The current understanding and advances in microbiome research and the relationship between the microbiome and the response to immunotherapy for RCC are also discussed. Improving our understanding of the role of the microbiome in RCC treatment will facilitate the development of microbiome targeting therapies to modify the tumor microbiome and improve treatment outcomes. [ABSTRACT FROM AUTHOR]

To evaluate the utility of different risk assessments in non-muscle-invasive bladder cancer (NMIBC) patients, a total of 178 NMIBC patients from Chungbuk National University Hospital (CBNUH) were enrolled, and the predictive value of the molecular signature-based subtype predictor (MSP888) and risk calculators based on clinicopathological factors (EORTC, CUETO and 2021 EAU risk scores) was compared. Of the 178 patients, 49 were newly analyzed by the RNA-sequencing, and their MSP888 subtype was evaluated. The ability of the EORTC, MSP888 and two molecular subtyping systems of bladder cancer (Lund and UROMOL subtypes) to predict progression of 460 NMIBC patients from the UROMOL project was assessed. Cox regression analyses showed that the MSP888 was an independent predictor of NMIBC progression in the CBNUH cohort (p = 0.043). Particularly in patients without an intravesical BCG immunotherapy, MSP888 significantly linked with risk of disease recurrence and progression (both p < 0.05). However, the EORTC, CUETO and 2021 EAU risk scores showed disappointing results with respect to estimating the NMIBC prognosis. In the UROMOL cohort, the MSP888, Lund and UROMOL subtypes demonstrated a similar capacity to predict NMIBC progression (all p < 0.05). Conclusively, the MSP888 is favorable for stratifying patients to facilitate optimal treatment. [ABSTRACT FROM AUTHOR]

Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK. [ABSTRACT FROM AUTHOR]

Background: We do not yet fully understand how the subtalar joint position is related to the varus osteoarthritic ankle joint. The purposes of this study were (1) to investigate the coronal orientation of the calcaneus relative to the talus according to the ankle osteoarthritis stage, talar tilt (TT), and (2) to determine if there is TT threshold at which apparent subtalar compensation begins to fade. Methods: We retrospectively reviewed 132 ankles that underwent weightbearing computed tomography (WBCT) for varus ankle osteoarthritis. The TT, subtalar inclination angle (SIA), and calcaneal inclination angle (CIA) were measured using WBCT. Ankles were divided into 5 groups according to Takakura stage and 2 groups according to the apparent compensation status of the subtalar joint and compared the index of the inclination of the subtalar joint relative to the ankle (SIA) or the index of the inclination of the calcaneus relative to the ankle (CIA). Additionally, we explored the relationship between SIA or CIA and the TT. Results: Apparent subtalar compensation (SIA and CIA) was significantly lower in Takakura stages 3b and 4. The SIA and CIA significantly differed according to the apparent compensation status (P <.001 and P =.030, respectively). The CIA of the noncompensated group varied widely, whereas the SIA was relatively constant. Furthermore, TT was greater than 9.5, which indicated a high probability of a noncompensated heel (sensitivity, 92.6%; specificity, 89.7%). Conclusion: The position of the calcaneus appears compensatory with coronal plane orientation in varus ankle osteoarthritis when the TT is ≤9.5 degrees. Level of Evidence: Level IV, case series. [ABSTRACT FROM AUTHOR]

The role of vascular smooth muscle cells (VSMCs) in vascular calcification, which is related to chronic kidney disease (CKD), has been studied in greater detail in the major arteries relative to the peripheral arteries. We compared the calcifying characteristics of peripheral VSMCs relative to non-pathologic major VSMCs in patients with severe peripheral artery disease (PAD). We isolated peripheral VSMCs from the posterior tibial artery of 10 patients with CKD who underwent below-knee amputation for critical limb ischemia (CLI). Using normal human aortic VSMCs as a control group, we cultured the cells in normal and high phosphate media for 10 days, and subsequently tested by immunofluorescence staining. We compared the calcification levels between the two groups using various assays, tests for cell viability, and scanning electron microscopy. As a result, calcification of pathologic peripheral VSMCs increased significantly with time (p = 0.028) and was significantly higher than that in human aortic VSMCs in calcium assays (p = 0.043). Dead cells in the pathologic VSMC group were more distinct in high phosphate media than in human aortic VSMCs. In conclusion, VSMCs from the peripheral artery of patients with severe CKD and CLI who underwent amputation surgery showed marked calcifying characteristics compared to normal human aortic VSMCs. [ABSTRACT FROM AUTHOR]

Category: Ankle Arthritis; Other Introduction/Purpose: It is unknown whether perioperative bisphosphonate (BP) use reduces revision rates in total ankle replacement arthroplasty (TAR) although its effect has been demonstrated to be effective in reducing revision rates in total knee or hip replacement arthroplasty. Therefore, the purpose of this study was 1) to investigate whether there is a relationship between the use of BP and the revision rate of TAR, and (2) to determine the effect of BP medication period on the revision rate of TAR. Our hypothesis was that the use of BP would lower the revision rate of TAR. Methods: We reviewed National Health Insurance Service data based on national health insurance service claim data and health care utilization, health screening, socio-demographic variables, medication history, operation codes, and mortality data for 50 million Koreans. From 2002 to 2014, 6391 of 7300 patients who underwent TAR were BP non-users, while 909 patients were BP users. The revision rate according to BP medication and co-morbidities was investigated. The Kaplan-Meier estimate and extended Cox proportional hazard model were also used. Results: The revision rate of TAR was 7.9% for BP users and 9.5% for BP non-users, which showed no significant difference (p=0.251). Implant survival over time decreased constantly. Adjusted hazard ratio for hypertension was 1.242 (p=0.017), while other co-morbidities such as diabetes had no effect on revision rate of TAR. Conclusion: We found that the perioperative BP use do not reduce the revision rate of TAR. Co-morbidities except hypertension did not affect the revision rate of TAR. More research regarding various factor affecting revision of TAR could be warranted. [ABSTRACT FROM AUTHOR]