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Introduction: Periprosthetic joint infection after total knee arthroplasty (TKA) is a devastating complication and different risk factors, including hyperglycemia and increased glucose variability, have been suggested for this condition in previous literature. Our study aims to investigate the risk factors for postoperative hyperglycemia and glucose variability in patients undergoing unilateral primary TKA with continuous glucose monitoring (CGM) technology. Methods: Demographic factors, diabetic statuses, hemoglobin A1c (HbA1c) levels, and fructosamine levels of patients undergoing unilateral primary TKA were recorded preoperatively. These patients would either received 16 mg intravenous dexamethasone or no dexamethasone before their surgery as part of perioperative management. From the day of admission to postoperative day 4, CGM device monitored these patients' blood glucose level, time of hyperglycemia, and glucose variability. Correlation and multivariate regression analysis were performed between the risk factors and the outcome measures, with multicollinearity between the predictor variables checked, to find out the most potent risk factors for postoperative hyperglycemia. Results: Eighty-three patients with primary unilateral TKA were analyzed. Diabetic, prediabetic, and nondiabetic patients were composed of 26.5%, 47.0%, and 26.5%, respectively. The average of HbA1c and fructosamine level was 6.0% and 249.3 mmol/L, respectively; 65.1% of the patients received 16 mg dexamethasone perioperatively. Multivariate regression analysis found that HbA1c, fructosamine, and dexamethasone injections are the significant risk factors for the percentage of time in hyperglycemia (R 2 = 0.374, p < 0.001) and average blood glucose level (R 2 = 0.493, p < 0.001), with HbA1c having the highest standardized coefficient, followed by fructosamine and dexamethasone injections. Although dexamethasone usage was significant in multivariate regression analysis on predicting glucose variability, the effect size of the model is very weak (R 2 = 0.05, p < 0.05). Conclusion: The most potent risk factor for hyperglycemic time and increased average blood glucose is HbA1c level, followed by fructosamine level and dexamethasone injections. No strong correlation was found between the factors in our study and patients' glucose variability. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to characterize the in-situ mechanical property and morphology of individual collagen fibril in osteoarthritic cartilage using indentation-type atomic force microscopy (IT-AFM).Methods: The specimens with intact articular cartilage (AC), mild to severe degenerated cartilage from osteoarthritis (OA) were collected with informed consent from the postmenopausal women who underwent hip or knee arthroplasty. The fresh specimens were cryo-sectioned by layers with 50μm thick for each from the articular surface to calcified cartilage, and then processed for AFM imaging and nanoindentation test. For each layer, a total of 20 collagen fibrils were randomly selected for testing. AFM tips with the nominal radius less than 10nm were employed for probing the individual collagen fibril, and the obtained cantilever deflection signal and displacement were recorded for calculating its elastic modulus.Results: An intact AC exhibited a gradation in elastic modulus of collagen fibrils from articular surface (2.65 ± 0.31 GPa) to the cartilage-bone interface (3.70 ± 0.44 GPa). It was noted in mildly degenerated OA cartilage that the coefficient of variation for mechanical properties of collagen fibers, ranging from 25% to 48%, significantly increased as compared with intact one (12%). The stiffened collagen fibrils occurred at either articular surface (3.11 ± 0.91 GPa) or the cartilage-bone interface (5.64 ± 1.10 GPa), accompanied by loosely organized meshwork with advancement of OA cartilage degeneration. It was echoed by histological findings of OA cartilage, including fibrotic changes of surface region and tidemark irregularities.Conclusion: The stiffened collagen fibrils in AC occurred with OA onset and progression, not only at articular surface but also the cartilage-bone interface. [ABSTRACT FROM AUTHOR]

Anteroposterior radiographs that included the whole tibia were taken before and after 75 total knee arthroplasties in 48 patients. The same tibial extra-medullary alignment guide system was used in every knee. The average tibial component alignment was 0.4 (SD 2.5, range -4.9 to 6.4) degrees of valgus post-operatively. 59 tibial components (78.7%) had a tibial cut within 3 degrees from being perpendicular to the mechanical axis, ten were too valgus (13.3%) and six were too varus (8%). The chance of the tibial components becoming too varus was higher if there was lateral tibial bowing, compared with no tibial bowing (p=0.048). A smaller lateral width of the leg increased the chance of the tibial components becoming too valgus (p=0.047). [ABSTRACT FROM AUTHOR]

Objective: To determine if the patients' or their guardians' perception of their home readiness compares with the Modified Postanaesthetic Discharge Score System (MPDSS).Methods: Not less than one hour after discharge from the post anaesthetic care unit, the patient or patients' guardian was given a set of questions that he/she answered. The questions asked if the patient felt fit enough to be discharged. The investigator, unaware of the answers, assessed the patient using the MPDSS. Patients with MPDSS score >9 were considered fit for home discharge with escort. Both admission and readmission were recorded.Results: Data from 119 patients showed good correlation between the patients' perception of need to stay longer and the MPDSS (p<0.001). Similarly both patients' prediction and MPDSS indicated the need for admission (p<0.001 and p=0.003 respectively).Conclusions: Both patients' perception and MPDSS were indicative of fitness of discharge. A number of patients did not feel the need to stay longer despite having discomfort. Some patients would have preferred to see an anesthetist before being discharged. This was more common in paediatric cases. [ABSTRACT FROM AUTHOR]

Background: The usefulness of the PFA-100 in assessing the risk of bleeding in non-cardiac surgery is not clear. This study aims to examine this by correlating preoperative PFA-100 measurement with perioperative bleeding in patients receiving cyclooxygenase (COX) inhibitors.Methods: PFA-100 with adenosine-5'-diphosphate (ADPCT) and epinephrine (EPICT) cartridges were measured before operation in consecutive patients undergoing elective total knee replacement and taking different COX inhibitors. Surgery and anaesthesia were performed by the same team using standardized techniques. Intraoperative blood loss and postoperative drain output were recorded by anaesthetists and nurses blinded to the PFA-100 measurements. Surgeons, similarly blinded, were asked to rate the quality of haemostasis. Correlation was sought between these data and PFA-100 measurements.Results: Thirty patients were studied, involving 51 knees. Preoperative PFA-100 EPICT was correlated with drain output (r=0.30, P=0.03). The correlation becomes stronger when a 20% in vitro haemodiluted sample was used for measurement (r=0.42, P=0.01). Receiver-operating characteristic curve analysis using the diluted measurements [area under curve (AUC) 0.74 (95% CI 0.54-0.94)] suggested using a cut-off value of 188 s for EPICT, which will predict excessive drain output with 89% sensitivity, 54% specificity, and a likelihood ratio of 1.93. Diluted EPICT was also correlated with surgeon rating of haemostasis (r=0.36, P=0.04) although none of the measurements correlated with intraoperative blood loss.Conclusions: Preoperative PFA-100 prolongation is correlated with increased postoperative drain output. It can be a potentially useful preoperative measurement in patients taking COX inhibitors. [ABSTRACT FROM AUTHOR]

Bone health screening is crucial before and during androgen deprivation therapy (ADT) for prostate cancer, yet changes in bone mineral density during ADT are often overlooked. To improve surveillance rates, we developed an auto-recruit path integrated into the outpatient system, where a pop-up reminder prompts physicians to arrange bone health screenings when ADT is prescribed without a dual-energy x-ray absorptiometry (DXA) screening in the past year. If selected, the system orders DXA and related examinations automatically. We retrospectively reviewed DXA screening rates from 2000 to 2018. During that period, only 286 out of 3,019 patients (9.5%) received DXA screenings. After implementing the auto-recruit system, 251 out of 747 eligible patients (33.6%) were screened from March 2021 to February 2022. Participants using ADT for over a year had worse T-scores and higher osteoporosis rates (34.5% vs. 23.2%) compared to those using ADT for less than a year. Post-screening, there was a significant increase in calcium supplement and bone protective agent use, highlighting improved patient awareness and proactive bone health management. In conclusion, bone health screening for prostate cancer patients on ADT remains an unmet need. The auto-recruit path in the outpatient system effectively increases screening rates and enhances bone health management., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study investigated the utilization of kidney-sparing surgery (KSS) as an alternative option to radical nephroureterectomy (RNU) in managing upper urinary tract urothelial carcinoma (UTUC) patients., Objective: Our study aimed to compare the functional outcomes and oncological outcomes between KSS and RNU., Material and Methods: We retrospectively analyzed 252 patients with UTUC without clinical node positivity or metastasis who had been treated with either RNU or KSS. We collected information on each patient, including clinicopathological factors, renal function variations, and oncological outcomes. Hemodialysis-free survival (HDFS), stage 4 chronic kidney disease (CKD4) progression-free survival (PFS), recurrence-free survival (RFS), and overall survival (OS) were assessed using inverse probability of treatment weighting (IPTW)-weighted Kaplan-Meier analysis. The hazard ratio for oncological and functional outcomes of KSS was analyzed using the Cox proportional hazards model., Results: The OS at 8 years was 77.06% (RNU) and 70.59% (KSS) and did not significantly differ between the two groups (p = 0.691), although the KSS group experienced a higher recurrence rate. Functional outcomes indicated no significant difference in postoperative renal function at 1 year; however, KSS was associated with better preservation of renal function (23.44% vs. 28.23%), albeit not statistically significant (p = 0.055). Kaplan-Meier analysis revealed no significant disparities in CKD4 PFS between the KSS and RNU groups involved in the study (p = 0.089), although the KSS group displayed poorer HDFS than the RNU group (p = 0.001)., Conclusion: KSS had no compromising survival outcomes when compared with RNU, not only in low-risk patients but also in high-risk patients with a normal contralateral kidney. The efficacy of renal function preservation was presented in this study, however the results were below our expectations., Competing Interests: Disclosures Yu-Chieh Wang, Jian-Ri Li, Chuan-Shu Chen, Shian-Shiang Wang, Cheng-Kuang Yang, Kun-Yuan Chiu, and Chiann-Yi Hsu have no conflicts of interest to declare that may be relevant to the contents of this study. Ethics approval This study was retrospectively performed on data from an Independent Review Board-approved study (IRB No. CE23551B)., (© 2024. The Author(s).)

Aberrant PI3K/Akt activation is linked to prostate cancer (PCa) malignancy, while androgen receptor (AR) is critical in early-stage PCa development. Investigating the interaction between these pathways is crucial for PCa malignancy. Our previous study demonstrated that p35-CDK5 mediates post-translational modifications of AR, STAT3, and p21 CIP1 , eventually promoting PCa cell growth. This study revealed the role of p35-CDK5 in between PI3K/Akt and AR by utilizing LNCaP and 22Rv1 cells. Through the TCGA database analysis, we observed a positive correlation between PTEN and p35 expression, implying a potential negative correlation between PI3K/Akt activation and p35-CDK5. Inhibiting PI3K/Akt with LY294002, Capivasertib (AZD5363), or using an inactive Akt mutant significantly increased p35 expression and subsequently enhanced AR stability and activation in PCa cells. On the other hand, CDK5-knockdown reversed these effects. The involvement of the β-catenin/Egr1-axis was observed in regulating PI3K/Akt inhibition and p35-CDK5 activation, implying a possible mechanistic connection. Importantly, CDK5 knockdown further reduced PI3K/Akt-inhibition-induced AR and cell viability maintenance, suggesting a compensatory role for CDK5-AR in maintaining cell viability under Akt inhibition. In conclusion, PI3K/Akt inhibition could trigger p35-CDK5-dependent AR activation and cell viability, highlighting p35-CDK5 as a critical link connecting PI3K/Akt inhibition to AR activation and pivotal in PCa cell resistance to PI3K/Akt blockade., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We report the rare entity of ulcerative colitis-related severe enteritis (UCRSE) following colectomy in a child. This entity has been described primarily in adults and is characterised by diffuse enteritis with histology identical to ulcerative colitis (UC). The mainstay treatment is steroids and in recent years anti-tumour necrosis factor agents.A boy in early adolescence required urgent colectomy for medically refractory severe acute colitis. Colectomy specimen histology confirmed UC. Postoperatively, he developed fevers, severe abdominal pain and excessive stoma output (5 L/day). Endoscopy revealed severe extensive enteritis, histologically resembling UC. Infliximab (IFX) was commenced with significant improvement. He remains asymptomatic 28 months post-colectomy on maintenance IFX monotherapy. To our knowledge, this is the youngest patient with this complication.This case illustrates the need to consider UCRSE in a child with otherwise unexplained fever, severe abdominal pain and high stoma output post colectomy. IFX monotherapy is a successful treatment option., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Prostate cancer (PC) treatment, particularly androgen deprivation therapy (ADT), remains pivotal, albeit linked to increased fracture risk due to osteoporosis. The advent of novel hormonal agents (NHAs) has spurred inquiries into their influence on bone health. This study aimed to evaluate the impact of NHAs on bone health in patients receiving combination therapy. We conducted a retrospective analysis using Taiwan's National Health Insurance Research Database, encompassing men aged 45 and above diagnosed with PC without bone metastasis and undergoing ADT between 2000 and 2018. The study involved 25,949 patients, categorized into those receiving standard ADT (n = 25,166) and those on NHA combination therapy (n = 783). Our analysis delved into fracture risk, comorbidities, and osteoporosis treatments. Patients on NHA combination therapy faced significantly higher risks of any osteoporotic fracture and major osteoporotic fracture than those on ADT alone (HR = 1.29, 95% CI 1.04-1.61; HR = 1.37, 95% CI 1.06-1.75, respectively). Notably, age emerged as a critical factor, with the highest risk observed in those aged 90 or above. The 5-year overall survival rates were lower for patients who experienced any osteoporotic fracture, major osteoporotic fracture, and hospitalization due to osteoporotic fracture compared to those who did not experience these fractures (51.5% vs. 56.5%, 47.1% vs. 56.7%, and 48.2% vs. 56.3%, respectively, p < 0.001). Furthermore, patients not using any bone-modifying agents had the highest risk for all fracture types. In conclusion, NHA combination therapy in PC patients potentially escalates the risk of osteoporotic fractures, especially in older individuals. Our findings underscore the pivotal role of osteoporosis treatments in preventing fractures, emphasizing the importance of evaluating fracture risk in patients undergoing NHA combination therapy., (© 2024. The Author(s).)

A substantial proportion of Hong Kong's aging population suffers from osteoarthritis in both knees. Bilateral total knee arthroplasty (BTKA) is a surgical option for addressing this condition and can be performed via two approaches: simultaneous BTKA (SimBTKA) and staged BTKA (StaBTKA). We compared the cost-effectiveness and safety of these two methods in our institution. We retrospectively reviewed 2,372 patients (SimBTKA, 772; StaBTKA, 1,600; females, 1,780; males, 592; mean age at SimBTKA, 70.4 ± 7.99 years; mean age at StaBTKA, 66.4 ± 7.50 years; p  < 0.001) who underwent BTKA in our institution from 2001 to 2022. Patients were categorized according to the surgical approach. Patients undergoing BTKA in our institution were included. Particularly for SimBTKA, patients were assessed by anesthetists to be medically fit before undergoing the procedure according to their age, American Society of Anesthesiologists status, and osteoarthritis severity. The primary outcome was the length of stay (LOS) after surgery. The secondary outcomes were the 30-day unintended readmission, intensive care unit (ICU) admission, and death. SimBTKA had a shorter mean total LOS (acute hospital + rehabilitation center; SimBTKA, 13.09 days; StaBTKA, 18.12 days; p  < 0.001) and mean LOS in acute hospital (SimBTKA, 7.70 days; StaBTKA, 10.42 days; p  < 0.001). However, no significant difference was found in the mean LOS in rehabilitation centers (SimBTKA, 5.47 days; StaBTKA, 6.32 days; p  > 0.05) between the two approaches. The 30-day unintended readmission rate was lower in SimBTKA (SimBTKA, 2.07%; StaBTKA, 3.30%; odds ratio [OR] = 1.60; p  > 0.05) but statistically insignificant. SimBTKA was less costly than StaBTKA by US$ 8,422.22 per patient. No significant differences in ICU admission and death rates were found ( p  > 0.05) between the two groups. SimBTKA had a shorter LOS and lower cost than StaBTKA and comparable complication rates. Therefore, SimBTKA should be indicated in medically stable patients., Competing Interests: None declared., (Thieme. All rights reserved.)

Background and Objectives: Ureteral reconstruction is aimed at maintaining ureteral patency without the need for long-term catheters like ureteral stents or percutaneous nephrostomies. Different surgical strategies are adopted based on the etiology, the location of the injury, and the severity of the injury. We aimed to analyze the parameters that can predict which patients might not be free from further catheterization after reconstruction. Materials and Methods: This study included patients who underwent ureteral reconstruction from January 2007 to December 2021. The success of ureteral reconstruction was defined as being free from further catheterization after the operation. Results: A total of 184 patients underwent ureteral reconstruction. Malignant disease with ureteral invasion and iatrogenic injuries accounted for 79.9% of the cases. The majority (79.3%) did not have to undergo subsequent interventions. Predictors for a failed result of ureteral reconstruction included a history of radiotherapy (OR = 2.75, p = 0.01), chronic kidney disease (CKD) (OR = 3.42, p < 0.001), and an upper ureteric location of the injury (OR = 5.68, p = 0.042). Conclusions: A history of radiation therapy, an upper third ureteric location of the injury, and CKD were identified as predictors of a failed ureteral reconstruction. Malignant diseases, surgical methods, and repair techniques did not significantly affect the outcome of the operation.

Introduction: Visceral metastasis is an important predictor for poor outcomes in prostate cancer, however, the prognostic significance surrounding the specific sites of visceral metastasis remains unclear. The aim of this study was to evaluate the impact of different visceral metastatic sites on survival in patients with prostate cancer., Methods: We identified patients with metastatic prostate cancer between January 1, 2010 and December 31, 2023 using the TriNetX database. Patients were divided into 4 cohorts according to their specific metastatic sites: lung metastases, brain metastases, liver metastases, and bone metastases. Survival analysis was calculated using the Kaplan-Meier method and Cox regression models., Results: In total, 59,875 patients diagnosed with metastatic prostate cancer were identified, with 39,495 (65.2%) having bone metastases, 7,573 (12.5%) lung metastases, 5,240 (8.7%) brain metastases, and 7,567 (12.5%) liver metastases. The median overall survival was 44.4 months for patients with bone metastases, 31.9 months for lung metastases, 9.6 months for brain metastases, and 10 months for liver metastases. Lung metastases were associated with an improved survival when compared with liver and brain metastases. For patients with two visceral metastatic sites or concomitant bone metastases, liver metastases were related to worse outcomes. Asian patients experienced better OS than Caucasian and African American patients in visceral metastatic prostate cancer., Conclusion: Patients with lung metastases experienced better survival outcomes in prostate cancer with only one visceral metastatic site. Liver metastases were associated with worse outcomes when there were two visceral metastatic sites combined or concomitant bone metastases. Asian patients displayed improved survival rates when compared with both Caucasian and African American patients in visceral metastatic prostate cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Non-metastatic castration-resistant prostate cancer (nmCRPC) is an asymptomatic condition with the potential to progress to metastasis. Novel hormonal agents (NHAs) are currently considered the gold standard treatment for nmCRPC, offering significant survival benefits. However, further evidence is needed to determine whether there are differences in the performance of these drugs among Asian populations., Methods: This retrospective analysis of nmCRPC patients aims to compare the efficacy and safety of three NHAs-apalutamide, darolutamide, and enzalutamide. Data were collected from two prominent prostate care centers in Taichung, Taiwan. Patient characteristics, treatment details, PSA responses, and adverse events were analyzed. Statistical comparisons were performed, and the study received Institutional Review Board approval., Results: Total of 64 patients were recruited in this study, including 29 darolutamide, 26 apalutamide, and 9 enzalutamide patients. Baseline characteristics varied between the three patient groups, but the treatment response still revealed similar results. The apalutamide group experienced more adverse events, notably skin rash. Discontinuation rates due to adverse events differed among the groups, and patients receiving darolutamide were less likely to discontinue treatment., Conclusion: This real-world study provides insights into NHA utilization in nmCRPC within the Taiwanese population. Adverse event profiles varied, emphasizing the need for individualized treatment decisions. The study underscores the importance of regional considerations and contributes valuable data for optimizing treatment outcomes in nmCRPC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Currently, glycopeptide quantitation is mainly based on relative quantitation due to absolute quantitation requiring isotope-labeled or standard glycopeptides which may not be commercially available or are very costly and time consuming to synthesize. To address this grand challenge, coulometric mass spectrometry (CMS), based on the combination of electrochemistry (EC) and mass spectrometry (MS), was utilized to quantify electrochemically active glycopeptides without the need of using standard materials. In this study, we studied tyrosine-containing glycopeptides, NYIVGQPSS(β-GlcNAc)TGNL-OH and NYSVPSS(β-GlcNAc)TGNL-OH, and successfully quantified them directly with CMS with a discrepancy of less than 5% between the CMS measured amount and the theoretical amount. Taking one step further, we applied this approach to quantify glycopeptides generated from the digestion of NIST mAb, a monoclonal antibody reference material. Through HILIC column separation, five N297 glycopeptides resulting from NIST mAb tryptic digestion were successfully separated and quantified by CMS for an absolute amount without the use of any standard materials. This study indicates the potential utility of CMS for quantitative proteomics research.