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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]

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.)

Anticipating implant sizes before total knee arthroplasty (TKA) allows the surgical team to streamline operations and prepare for potential difficulties. This study aims to determine the correlation and derive a regression model for predicting TKA sizes using patient-specific demographics without using radiographs. We reviewed the demographics, including hand and foot sizes, of 1,339 primary TKAs. To allow for comparison across different TKA designs, we converted the femur and tibia sizes into their anteroposterior (AP) and mediolateral (ML) dimensions. Stepwise multivariate regressions were performed to analyze the data. Regarding the femur component, the patient's foot, gender, height, hand circumference, body mass index, and age was the significant demographic factors in the regression analysis (R-square 0.541, p  < 0.05). For the tibia component, the significant factors in the regression analysis were the patient's foot size, gender, height, hand circumference, and age (R-square 0.608, p  < 0.05). The patient's foot size had the highest correlation coefficient for both femur (0.670) and tibia (0.697) implant sizes ( p  < 0.05). We accurately predicted the femur component size exactly, within one and two sizes in 49.5, 94.2, and 99.9% of cases, respectively. Regarding the tibia, the prediction was exact, within one and two sizes in 53.0, 96.0, and 100% of cases, respectively. The regression model, utilizing patient-specific characteristics, such as foot size and hand circumference, accurately predicted TKA femur and tibia sizes within one component size. This provides a more efficient alternative for preoperative planning., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Survivorship of medial unicompartmental knee arthroplasty (UKA) is technique-dependent. Correct femoral-tibial component positioning associates with improved survivorship. Image-free robotic-assisted unicompartmental knee arthroplasty enables preoperative and intraoperative planning of alignment and assessment of positioning prior to execution. This study aimed to compare the radiological outcomes between robotic-assisted UKA (R-UKA) and conventional UKA (C-UKA)., Methods: This retrospective case control study involved 140 UKA (82 C-UKA and 58 R-UKA) performed at an academic institution between March 2016 to November 2020, with a mean follow-up of 3 years. Postoperative radiographs were evaluated for mechanical axis and femoral-tibial component position. Component position was measured by two methods: (1) femoral-tibial component contact point with reference to four medial-to-lateral quadrants of the tibial tray and (2) femoral-tibial component contact point deviation from the center of the tibial tray as a percentage of the tibial tray width. Baseline demographics and complications were recorded., Results: There was a higher mean component deviation in C-UKA compared with R-UKA using method 2 (17.2% vs. 12.8%; P = 0.007), but no difference in proportion of zonal outliers using method 1 (4 outliers in C-UKA, 5.1% vs. 1 outlier in R-UKA, 1.8%; P = 0.403). R-UKA showed no difference in mean mechanical alignment (C-UKA 5° vs. R-UKA 5°; P = 0.250). 2-year survivorship was 99% for C-UKA and 97% for R-UKA. Mean operative time was 18 min longer for R-UKA (P < 0.001)., Conclusion: Image-free robotic-assisted UKA had improved component medio-lateral alignment compared with conventional technique., (© 2024. The Author(s).)

Background: The high co-prevalence of obesity and end-stage osteoarthritis requiring arthroplasty, with the former being a risk factor for complications during arthroplasty, has led to increasing interest in employing preoperative weight loss interventions such as bariatric surgery and diet modification. However, the current evidence is conflicting, and this study aimed to investigate the effect of weight loss intervention before arthroplasty in prospective randomized controlled trials., Methods: Four electronic databases (MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials) were searched for prospective randomized controlled trials that compared weight loss interventions with usual care from inception to October 2023 by following the PRISMA guidelines. The Cochrane risk of bias tool and GRADE framework were used to assess the quality of the studies. Meta-analyses were performed when sufficient data were available from 2 or more studies., Results: Three randomized controlled trials involving 198 patients were identified. Two studies employed diet modification, and one study utilized bariatric surgery. All three studies reported significant reductions in body weight and body mass index (BMI), and intervention groups had fewer postoperative complications. There was no difference in the length of stay between the intervention group and the control group. Variable patient-reported outcome measures were used by different research groups., Conclusion: Weight loss intervention can achieve significant reductions in body weight and body mass index before arthroplasty, with fewer postoperative complications reported. Further studies with different populations could confirm the effect of these interventions among populations with different obesity characteristics., (© 2024. The Author(s).)

GABAergic interneurons are poised with the capacity to shape circuit output via inhibitory gating. How early in the development of medial vestibular nucleus (MVN) are GABAergic neurons recruited for feedforward shaping of outputs to higher centers for spatial navigation? The role of early GABAergic transmission in assembling vestibular circuits for spatial navigation was explored by neonatal perturbation. Immunohistochemistry and confocal imaging were utilized to reveal the expression of parvalbumin (PV)-expressing MVN neurons and their perineuronal nets. Whole-cell patch-clamp recording, coupled with optogenetics, was conducted in vitro to examine the synaptic function of MVN circuitry. Chemogenetic targeting strategy was also employed in vivo to manipulate neuronal activity during navigational tests. We found in rats a neonatal critical period before postnatal day (P) 8 in which competitive antagonization of GABAergic transmission in the MVN retarded maturation of inhibitory neurotransmission, as evidenced by deranged developmental trajectory for excitation/inhibition ratio and an extended period of critical period-like plasticity in GABAergic transmission. Despite increased number of PV-expressing GABAergic interneurons in the MVN, optogenetic-coupled patch-clamp recording indicated null-recruitment of these neurons in tuning outputs along the ascending vestibular pathway. Such perturbation not only offset output dynamics of ascending MVN output neurons, but was further accompanied by impaired vestibular-dependent navigation in adulthood. The same perturbations were however non-consequential when applied after P8. Results highlight neonatal GABAergic transmission as key to establishing feedforward output dynamics to higher brain centers for spatial cognition and navigation., (© 2024. The Author(s).)

Introduction: Unicompartmental knee arthroplasty (UKA) is an effective surgical treatment for medial compartment arthritis of the knee, yet surgical outcomes are directly related to surgical execution. Robotic arm-assisted surgery aims to address these difficulties by allowing for detailed preoperative planning, real-time intraoperative assessment and haptic-controlled bone removal. This study aimed to compare the clinical and radiological outcomes between conventional manual mobile bearing and robot arm-assisted fixed bearing medial UKA in our local population., Materials and Methods: This is a retrospective case-control study of 148 UKAs performed at an academic institution with a minimum of 1-year follow-up. 74 robotic arm-assisted UKAs were matched to 74 conventional UKAs via propensity score matching. Radiological outcomes included postoperative mechanical axis and individual component alignment. Clinical parameters included a range of motion, Knee Society knee score and functional assessment taken before, 6 and 12 months after the operation., Results: Robot arm-assisted UKA produced a more neutral component coronal alignment in both femoral component (robotic -0.2 ± 2.8, manual 2.6 ± 2.3; P = 0.043) and tibial component (robotic -0.3 ± 4.0, manual 1.7 ± 5.3; P < 0.001). While the postoperative mechanical axis was comparable, robot arm-assisted UKA demonstrated a smaller posterior tibial slope (robotic 5.7 ± 2.7, manual 8.2 ± 3.3; P = 0.02). Clinical outcomes did not show any statistically significant differences., Conclusion: Compared with conventional UKA, robotic arm-assisted UKA demonstrated improved component alignment and comparable clinical outcomes. Improved radiological accuracy with robotic-arm assistance demonstrated promising early results., (© 2023. Arthroplasty Society in Asia.)

Purpose: Cross-linked polyethylene (PE) has been used with great clinical success in total hip arthroplasty (THA) since its debut in the late 1990's. However, reports regarding this bearing couple near the end of its second decade of service are still scant. The aim of this study was to first determine the long term clinical and radiological results and second Investigate what factors affect wear rates using a metal-on-crosslinked PE bearing articulation., Methods: 55 THAs using a single brand of cross-linked liner, cementless cup and 28 mm hip ball were performed in 44 patients. Age, sex, Charlson Comorbidity Index (CCI) and need for revision surgery were recorded. Linear and volumetric wear was determined using the Martell method., Results: Mean age at operation was 51.2 (29-73 ± 12.1) years. Mean duration of follow-up was 16.9 years (range 15.0-20.1 ± 1.1 years). Osteolysis was not present in the latest follow-up radiographs. Median linear and volumetric wear rate was 0.038 mm/year (95% CI 0.032-0.047) and 7.115mm3/year (95% CI 6.92-17.25) respectively. Acetabular component position was not found to be related to both linear and volumetric wear. No significant difference was found in the linear and volumetric wear rates of thinner and thicker liners (8 mm or below and > 8 mm) (p = 0.849 and p = 0.64 respectively)., Conclusion: Metal-on-crosslinked PE is associated with low linear and volumetric wear rates which has virtually obviated osteolysis and has translated to excellent survivorship even at long term follow up. In-vivo oxidation does not appear to be of clinical concern at this point., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

The usage of telemedicine and telehealth services has grown tremendously and has become increasingly relevant and essential. Technological advancements in current telehealth services have supported its use as a viable alternative tool to conduct visits for consultations, follow-up, and rehabilitation in total joint arthroplasty. Such technology has been widely implemented, particularly during the coronavirus 2019 (COVID-19) pandemic, to deliver postoperative rehabilitation among patients receiving total joint arthroplasty (TJA), further demonstrating its feasibility with a lower cost yet comparable clinical outcomes when compared with traditional care. There remains ample potential to utilize telemedicine for prehabilitation to optimize the preoperative status and postoperative outcomes of patients with osteoarthritis. In this review, various implementations of telemedicine within total joint arthroplasty and future application of telemedicine to deliver tele-prehabilitation in TJA are discussed., (© 2023. The Author(s).)

Background: Total knee arthroplasty (TKA) is a cost-effective procedure, but it is also associated with substantial postoperative pain. The present study aimed to compare pain relief and functional recovery after TKA among groups that received intravenous corticosteroids, periarticular corticosteroids, or a combination of both., Methods: This randomized, double-blinded clinical trial in a local institution in Hong Kong recruited 178 patients who underwent primary unilateral TKA. Six of these patients were excluded because of changes in surgical technique; 4, because of their hepatitis B status; 2, because of a history of peptic ulcer; and 2, because they declined to participate in the study. Patients were randomized 1:1:1:1 to receive placebo (P), intravenous corticosteroids (IVS), periarticular corticosteroids (PAS), or a combination of intravenous and periarticular corticosteroids (IVSPAS)., Results: The pain scores at rest were significantly lower in the IVSPAS group than in the P group over the first 48 hours (p = 0.034) and 72 hours (p = 0.043) postoperatively. The pain scores during movement were also significantly lower in the IVS and IVSPAS groups than in the P group over the first 24, 48, and 72 hours (p ≤ 0.023 for all). The flexion range of the operatively treated knee was significantly better in the IVSPAS group than in the P group on postoperative day 3 (p = 0.027). Quadriceps power was also greater in the IVSPAS group than in the P group on postoperative days 2 (p = 0.005) and 3 (p = 0.007). Patients in the IVSPAS group were able to walk significantly further than patients in the P group in the first 3 postoperative days (p ≤ 0.003). Patients in the IVSPAS group also had a higher score on the Elderly Mobility Scale than those in the P group (p = 0.036)., Conclusions: IVS and IVSPAS yielded similar pain relief, but IVSPAS yielded a larger number of rehabilitation parameters that were significantly better than those in the P group. This study provides new insights into pain management and postoperative rehabilitation following TKA., Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H483 )., (Copyright © 2023 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Background: Machine learning is a promising and powerful technology with increasing use in orthopedics. Periprosthetic joint infection following total knee arthroplasty results in increased morbidity and mortality. This systematic review investigated the use of machine learning in preventing periprosthetic joint infection., Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed was searched in November 2022. All studies that investigated the clinical applications of machine learning in the prevention of periprosthetic joint infection following total knee arthroplasty were included. Non-English studies, studies with no full text available, studies focusing on non-clinical applications of machine learning, reviews and meta-analyses were excluded. For each included study, its characteristics, machine learning applications, algorithms, statistical performances, strengths and limitations were summarized. Limitations of the current machine learning applications and the studies, including their 'black box' nature, overfitting, the requirement of a large dataset, the lack of external validation, and their retrospective nature were identified., Results: Eleven studies were included in the final analysis. Machine learning applications in the prevention of periprosthetic joint infection were divided into four categories: prediction, diagnosis, antibiotic application and prognosis., Conclusion: Machine learning may be a favorable alternative to manual methods in the prevention of periprosthetic joint infection following total knee arthroplasty. It aids in preoperative health optimization, preoperative surgical planning, the early diagnosis of infection, the early application of suitable antibiotics, and the prediction of clinical outcomes. Future research is warranted to resolve the current limitations and bring machine learning into clinical settings., (© 2023. The Author(s).)

Background: Isolated liner exchange is an option to address polyethylene wear after total hip arthroplasty (THA). The liner can be fixed with either the original locking mechanism or cemented into the acetabular cup. Whether the method used for liner fixation has any bearing on the outcomes in the first and second decade after surgery is still unclear., Methods: Data for all patients who had undergone isolated liner exchange surgery in our institution between April 1995 and January 2015 were retrieved. Patients were classified according to the type of polyethylene liner (conventional or highly crosslinked polyethylene) and the locking mechanism used (original locking mechanism or cemented). Survivorship and revision rates were compared among different subgroups. A total of 118 isolated liner exchanges were performed and patients had a mean duration of follow-up of 13 years (range, 5 to 25)., Results: Overall estimated mean survivorship was 17 years. Use of highly crosslinked polyethylene (HXLPE) had a lower re-revision rate compared to conventional liners (10.5 versus 46.9%) (P < .001). The re-revision rate of exchanges using HXLPE was not affected by the type of fixation (original locking mechanism 11.1 versus cement 10.0%, P = .868). Conversely, using the original locking mechanism with a conventional liner had a higher re-revision rate compared to cemented conventional liners (58.3 versus 12.5%) (P = .024)., Conclusion: HXLPE liners should be used in insert exchange surgery whenever possible. Re-revision rate of exchanges using HXLPE was not affected by the fixation technique used. Cementing an insert into an acetabular component is associated with good survivorship at a mean of 13 years follow-up., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We report evidence for nonlinear modes in the ringdown stage of the gravitational waveform produced by the merger of two comparable-mass black holes. We consider both the coalescence of black hole binaries in quasicircular orbits and high-energy, head-on black hole collisions. The presence of nonlinear modes in the numerical simulations confirms that general-relativistic nonlinearities are important and must be considered in gravitational-wave data analysis.

Replication licensing, a prerequisite of DNA replication, helps to ensure once-per-cell-cycle genome duplication. Some DNA replication-initiation proteins are sequentially loaded onto replication origins to form pre-replicative complexes (pre-RCs). ORC and Noc3p bind replication origins throughout the cell cycle, providing a platform for pre-RC assembly. We previously reported that cell cycle-dependent ORC dimerization is essential for the chromatin loading of the symmetric MCM double-hexamers. Here, we used Saccharomyces cerevisiae separation-of-function NOC3 mutants to confirm the separable roles of Noc3p in DNA replication and ribosome biogenesis. We also show that an essential and cell cycle-dependent Noc3p dimerization cycle regulates the ORC dimerization cycle. Noc3p dimerizes at the M-to-G 1 transition and de-dimerizes in S-phase. The Noc3p dimerization cycle coupled with the ORC dimerization cycle enables replication licensing, protects nascent sister replication origins after replication initiation, and prevents re-replication. This study has revealed a new mechanism of replication licensing and elucidated the molecular mechanism of Noc3p as a mediator of ORC dimerization in pre-RC formation., (© 2023 Amin et al.)

Gastric cancer is the fifth most frequently occurring and the fourth most lethal malignant cancer worldwide. A bioactive protein (pPe O p) from Omphalia lapidescens exhibits significant inhibitory effects on gastric cancer cells. miRNA deep sequencing analysis shows that miR-30b-5p is significantly upregulated in HGC-27 cells treated with pPe O p. Verification results show that the expression level of miR-30b-5p is significantly increased in HGC-27 cells after pPe O p treatment. Additionally, miR-30b-5p is significantly downregulated in clinical gastric cancer tissues compared to that in adjacent normal tissues. Following pPe O p treatment and/or transfection with miR-30b-5p mimic, the proliferation, migration, and invasion of HGC-27 cells are significantly impaired. Immunofluorescence microscopy shows that pPe O p and/or miR-30b-5p destroy(s) microfilaments and microstructures and inhibit(s) the formation of pseudopodia. Bioinformatics analysis, dual-luciferase reporter assay, and western blot analysis confirm that miR-30b-5p downregulates Rac1/Cdc42 expression and activation by targeting RAB22A. Available data indicate that miR-30b-5p plays an anti-gastric cancer role in mediating pPe O p. pPe O p upregulates miR-30b-5p expression, which in turn inhibits RAB22A expression, resulting in a reduction in the expression and activation of Rac1 and Cdc42 and their downstream targets, thus destroying the cytoskeletal structure and inhibiting the proliferation, migration, and invasion of cancer cells.

MicroRNAs are noncoding RNAs with a typical length of 22 nucleotides that post-transcriptionally suppress gene expression by inducing target mRNA degradation and/or impairing translation in eukaryotes. Thousands of miRNA genes in the human genome are involved in various physiological and pathological processes. Each miRNA targets many different mRNAs, while each mRNA may be targeted by various miRNAs. Mini-chromosome maintenance (MCM2-7) protein complex functions as essential components of the pre-replicative complex (pre-RC) and forms a helicase together with other proteins to unwind the DNA duplex in S phase. MCM proteins are overexpressed in all cancer cells, while they are strictly regulated in normal cells, with no expression in non-proliferating normal cells. Here we report that miRNA-214-3p (miR-214) targets both MCM5 and MCM7. The level of miR-214 is lower in HepG2 and Hep3B hepatocellular carcinoma cells than the L-02 normal liver cells. Introduction of miRNA-214 mimic into HepG2 and Hep3B cells reduced the mRNA and protein levels of MCM5/7 and inhibited DNA replication, cell cycle progression, cell proliferation and colony formation. Comparatively, miRNA-214 mimic had little effect in L-02 cells. Importantly, miR-214 mimic can also inhibit the growth of HepG2 xenografts in nude mice. Our data suggest that miRNA-214 regulates DNA replication by targeting MCM5/7 and has the potential to be developed into a liver cancer drug. IMPLICATIONS: This study supports the notion that DNA replication-initiation proteins (DRIPs), including MCM2-7 proteins, are attractive anticancer targets. Furthermore, the potential of miR-214 as an anticancer agent, with activity against liver cancer cells but not normal livre cells, may be of high significance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In recent years, indications for genetic testing in prostate cancer (PC) have expanded from patients with a family history of prostate and/or related cancers to those with advanced castration-resistant disease, and even to early PC patients for determination of the appropriateness of active surveillance. The current consensus aims to provide guidance to urologists, oncologists and pathologists working with Asian PC patients on who and what to test for in selected populations., Methods: A joint consensus panel from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology was convened over a series of 5 physical and virtual meetings. A background literature search on genetic testing in PC was performed in PubMed, ClinicalKey, EBSCOHost, Ovid and ProQuest, and three working subgroups were formed to review and present the relevant evidence. Meeting agendas adopted a modified Delphi approach to ensure that discussions proceed in a structured, iterative and balanced manner, which was followed by an anonymous voting on candidate statements. Of 5 available answer options, a consensus statement was accepted if ≥ 75% of the panelists chose "Accept Completely" (Option A) or "Accept with Some Reservation" (Option B)., Results: The consensus was structured into three parts: indications for testing, testing methods, and therapeutic implications. A list of 35 candidate statements were developed, of which 31 were accepted. The statements addressed questions on the application of PC genetic testing data and guidelines to Asian patients, including patient selection for germline testing, selection of gene panel and tissue sample, provision of genetic counseling, and use of novel systemic treatments in metastatic castration-resistant PC patients., Conclusion: This consensus provides guidance to urologists, oncologists and pathologists working with Asian patients on indications for genetic testing, testing methods and technical considerations, and associated therapeutic implications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chiu, Lee, Chan, Chan, Cheung, Lam, Ma and Poon.)

Recent work applying the notion of pseudospectrum to gravitational physics showed that the quasinormal mode spectrum of black holes is unstable, with the possible exception of the longest-lived (fundamental) mode. The fundamental mode dominates the expected signal in gravitational wave astronomy, and there is no reason why it should have privileged status. We compute the quasinormal mode spectrum of two model problems where the Schwarzschild potential is perturbed by a small "bump" consisting of either a Pöschl-Teller potential or a Gaussian, and we show that the fundamental mode is destabilized under generic perturbations. We present phase diagrams and study a simple double-barrier toy problem to clarify the conditions under which the spectral instability occurs.

Background: Artificial intelligence is an emerging technology with rapid growth and increasing applications in orthopaedics. This study aimed to summarize the existing evidence and recent developments of artificial intelligence in diagnosing knee osteoarthritis and predicting outcomes of total knee arthroplasty., Methods: PubMed and EMBASE databases were searched for articles published in peer-reviewed journals between January 1, 2010 and May 31, 2021. The terms included: 'artificial intelligence', 'machine learning', 'knee', 'osteoarthritis', and 'arthroplasty'. We selected studies focusing on the use of AI in diagnosis of knee osteoarthritis, prediction of the need for total knee arthroplasty, and prediction of outcomes of total knee arthroplasty. Non-English language articles and articles with no English translation were excluded. A reviewer screened the articles for the relevance to the research questions and strength of evidence., Results: Machine learning models demonstrated promising results for automatic grading of knee radiographs and predicting the need for total knee arthroplasty. The artificial intelligence algorithms could predict postoperative outcomes regarding patient-reported outcome measures, patient satisfaction and short-term complications. Important weaknesses of current artificial intelligence algorithms included the lack of external validation, the limitations of inherent biases in clinical data, the requirement of large datasets in training, and significant research gaps in the literature., Conclusions: Artificial intelligence offers a promising solution to improve detection and management of knee osteoarthritis. Further research to overcome the weaknesses of machine learning models may enhance reliability and allow for future use in routine healthcare settings., (© 2022. The Author(s).)

Gastric cancer is the leading cause of cancer-related death worldwide. The aim of present study was to investigate the anti-tumor effect of purified Omphalia lapidescens protein (pPe O p) in gastric cancer. Microarray analysis was performed to find out differentially expressed genes in pPe O p-treated MC-4 gastric cancer cells. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) three signaling pathway was most likely to be altered based on bioinformatics analysis. Interleukin-6 (IL-6) and NSC74859 were used as the agonist and inhibitor of the JAK/STAT3 signaling pathway, respectively. Flow cytometry and MTS assay were used for cell proliferation and viability analysis in pPe O p-treated gastric cancer cell lines with IL-6 or NSC74859. The anti-tumor effect was increased when pPe O p were co-treated with IL-6, while decreased in inhibitor treatment. The expression of the crucial members in the pathway of MC-4 cells, including glycoprotein 130 (GP130), JAK1, JAK2, STAT3, p-STAT3, suppressor of cytokine signaling SOCS1 and SOCS3, was detected by western blotting. pPe O p exhibited promising anticancer effect in the xenograft nude mice model, established by STAT3 knock down gastric cancer cells.Thus, JAK/STAT3 inhibition partially contributed to the anticancer effect of pPe O p, which may serve as a novel strategy for gastric cancer.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1960385.

Introduction: Peri-prosthetic joint infection (PJI) was one of the main causes of revision of arthroplasty. In order to reduce wound complications and surgical site infections, close incisional negative pressure wound therapy (ciNPWT) has been introduced into arthroplasty. This study was designed to review the clinical benefits of the application of ciNPWT in revision arthroplasty., Methods: This was a single-centre retrospective comparative study approved by the Institutional Review Board. Patients, who underwent revision total knee arthroplasty or revision total hip arthroplasty at the author's institution from January 2016 to October 2019, were included in this study. The ciNPWT cohort included all eligible patients, who underwent operations from January 2018 to October 2019, with the use of ciNPWT(n = 36). The control cohort included all eligible patients, who underwent operations from January 2016 to December 2017 with the use of conventional dressing(n = 48). The incidences of wound complications were compared to both cohorts., Results: There was a statistically significant difference in the rate of superficial surgical site infection (SSI) between control cohort and ciNPWT cohort (12.5% in control vs 0% in ciNPWT, p = 0.035). However, there was no statistically significance of the overall wound complication rate for both cohorts. (14.6% in control vs 8.3% in ciNPWT, p = 0.504)., Conclusions: The application of ciNPWT could result in a lower rate of superficial surgical site infection when compared with conventional dressing among the patients undergoing revision total knee and total hip arthroplasties., Trial Registration: UW19-706., (© 2021. The Author(s).)

Background: Dual-mobility hip component is widely used in Europe and North America, because it effectively reduces hip dislocation in primary and revision total hip arthroplasties. However, reports were limited on the use of dual-mobility articulation in Asian populations., Purpose: The aim of this retrospective study was to review the use of modular dual-mobility hip articulation in Asian patients with the high risk factor for hip dislocation. We also discussed the potential concern on the use of dual-mobility articulation in Asian patients., Methods: From Jan 2018 to June 2019, 17 patients were included in this study. The mean age of the patients was (73.8 ± 9.5) years (range: 57-88 years). The mean size of acetabular cup and modular DM liner were (49.5 ± 3.4) mm (range, 46-58 mm) and (40.7 ± 3.4) mm (range, 38-48 mm), respectively. The mean follow-up period was (15.8 ± 3.9) months (range, 11-24 months). The primary outcome was the rate of hip dislocation. The secondary outcomes included the Harris Hip Score. Differences were considered statistically significant at p < 0.05., Results: Hip dislocation, loosening, peri-prosthetic fractures, or intra-prosthetic dislocation was not found in the series. The mean preoperative and postoperative Harris Hip Scores were 42.2 ± 17.2 (range, 15-80) and 74.7 ± 13.5 (range, 52-97), respectively, giving a mean improvement of 32.5 ± 17.2 (range, 4-72). The improvement was statistically significant (p < 0.05)., Conclusions: In Asian patients with high risk of hip dislocation, the use of modular dual-mobility hip component produces promising outcomes without hip dislocation, but the relatively small-sized acetabulum may limit it widespread application in other populations worldwide., Trial Registration: HKUCTR-2913 ., (© 2021. The Author(s).)

Background: Arthroplasty services worldwide have been significantly disrupted by the pandemic of coronavirus disease 2019 (COVID-19). This retrospective comparative study aimed to characterize its impact on arthroplasty services in Hong Kong., Methods: From January 1 to June 30, 2020, the patients of "COVID-19 cohort" underwent elective total hip or knee replacement in Hong Kong public hospitals. The cohort was compared to the "control cohort" during the same period in 2019. Data analysis was performed to compare the two cohorts' numbers of operations, hospital admission, orthopaedic clinic attendances, and waiting time., Results: A total of 33,111 patient episodes were analyzed. During the study period, the elective arthroplasty operations and hospitalizations decreased by 53 and 54%, respectively ( P  < 0.05). Reductions were most drastic from February to April, with surgical volume declining by 86% ( P  < 0.05). The primary arthroplasty operations decreased by 91% ( P  < 0.05), while the revision operations remained similar. Nevertheless, 14 public hospitals continued performing elective arthroplasty for patients with semi-urgent indications, including infection, progressive bone loss, prosthesis loosening, dislocation or mechanical failure of arthroplasty, and tumor. At the institution with the highest arthroplasty surgical volume, infection (28%) was the primary reason for surgery, followed by prosthesis loosening (22%) and progressive bone loss (17%). The orthopaedic clinic attendances also decreased by 20% ( P  < 0.05). Increases were observed in waiting time and the total number of patients on the waiting list for elective arthroplasty., Conclusions: Despite the challenges, public hospitals in Hong Kong managed to continue providing elective arthroplasty services for high-priority patients. Arthroplasty prioritization, infection control measures, and post-pandemic service planning can enhance hospital preparedness to mitigate the impact of current and future pandemics., Competing Interests: Competing interestsChun Hoi Yan and Peter KY Chiu are members of the Editorial Board of Arthroplasty and other authors declare that they have no competing interests. All authors were not involved in the journal’s review of or decisions related to this manuscript., (© The Author(s) 2021.)

Primary cilia are microtubule-based, antenna-like organelles, which are formed in G 0 phase and resorbed as cells re-enter the cell cycle. It has been reported that primary cilia can influence the timing of cell cycle progression. However, the molecular links between ciliogenesis and cell cycle progression are not well understood. The Fibroblast Growth Factor Receptor 1 Oncogene Partner (FOP) has been implicated in ciliogenesis, but its function in ciliogenesis is not clear. Here, we show that FOP plays a negative role in ciliogenesis. Knockdown of FOP promotes cilia elongation and suppresses cilia disassembly. In contrast, ectopic expression of FOP induces defects in primary cilia formation, which can be rescued by either pharmacological or genetic inhibition of Aurora kinase A which promotes cilia disassembly. Moreover, knockdown of FOP delays cell cycle re-entry of quiescent cells following serum re-stimulation, and this can be reversed by silencing Intraflagellar Transport 20 (IFT20), an intraflagellar transport member essential for ciliogenesis. Collectively, these results suggest that FOP negatively regulates ciliogenesis and can promote cell cycle re-entry by facilitating cilia disassembly., (Copyright © 2020 Jiang, Liu, Cheung, Amin and Liang.)

Hip fusion takedown to total hip replacement is a challenging operation. Neck osteotomy and acetabular component placement are technically demanding and often require fluoroscopic guidance. Robotic arm-assisted total hip arthroplasty enhances accuracy of preoperative planning and provides navigated guidance for neck osteotomy and haptic guidance on acetabular reaming and cup implantation. Fluoroscopic guidance is replaced by real-time navigation and on-screen data. This article describes how robotic arm assistance can simplify this complex operation., (© 2020 The Authors.)

Objectives: The study aimed to examine the anti-diabetic effects of Gynura divaricata (GD) and the underlying mechanism., Methods: Information about the chemical compositions of GD was obtained from extensive literature reports. Potential target genes were predicted using PharmMapper and analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). To validate the results from bioinformatics analyses, an aqueous extract of GD was administered to type 2 diabetic rats established by feeding a high-fat and high-sugar diet followed by STZ injection. Key proteins of the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway were investigated by immunoblotting., Results: The blood glucose of the rats in the GD treatment group was significantly reduced compared with the model group without treatment. GD also showed activities in reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (CREA). The levels of urine sugar (U-GLU) and urine creatinine (U-CREA) were also lowered after treatment with GD. Bioinformatics analysis showed that some pathways including metabolic pathways, insulin resistance, insulin signaling pathway, PPAR signaling pathway, bile secretion, purine metabolism, etc. may be regulated by GD. Furthermore, GD significantly increased the protein expression levels of PKM1/2, p-AKT, PI3K p85, and GLUT4 in the rat liver. In addition, the expression levels of key proteins in the fatty acid metabolism signaling pathway including AMPK, p-AMPK, PPARα, and CPT1α were significantly upregulated. The anti-apoptotic protein BCL-2/BAX expression ratio in rats was significantly upregulated after GD intervention. These results were consistent with the bioinformatics analysis results., Conclusions: Our study suggests that GD can exert hypoglycemic effects in vivo by regulating the genes at the key nodes of the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway.

Introduction: Total knee arthroplasty (TKA) in the elderly population is becoming increasingly prevalent. This study aimed to compare outcomes of patients aged ≥80 years with those aged < 80 years at time of TKA and to assess the effect of fast track peri-operative care on outcomes in the elderly., Materials and Methods: 422 TKAs were performed in aged ≥80 at the time of surgery between 2009 and 2018. A control group aged < 80 years (37-79 +/- 7.6) was established. Peri-operative mortality, complications, 30-day re-admission, length of stay (LOS) and rehabilitation parameters were recorded., Results: Mean age at operation for the ≥80's group and control group was 82.7 (80-93+/- 2.5) and 69.3 (37-79+/- 7.6) years respectively. Post-operative Knee Society Functional Assessment (KSFA) scores were higher in the control group (49 vs. 57, p = 0.003). Average LOS was longer in the ≥80's group (17.2 vs. 12.4 days respectively, p < 0.01). Mortality within 3 months of operation was 0.7% in the ≥80 group and 0% in the control group. Incidence of complications was comparable between the two groups at 12.8 and 12.9% for the group ≥80's and control groups respectively (p = 0.962). Patients ≥80 years, receiving fast track peri-operative care had significantly shorter LOS and higher post-operative KSFA scores at all time points post-operation and shorter LOS (p < 0.01) compared to those who received conventional rehabilitation. LOS was longer in the ≥80's group, which was likely related to higher levels of comorbidities. Complications were comparable in the two groups but were more severe in the elderly. Mortality rate after TKA was very low even in those over the age of 80. Younger patients benefited more in terms of functional improvement after TKA., Conclusion: TKA is a safe and efficacious procedure for the elderly. More severe complications, longer length of stay and smaller gains in functional improvement can be expected in the elderly compared to younger patients. Fast track peri-operative care is useful in improving outcomes after TKA for elderly patients., (© 2020. The Author(s).)

Eukaryotic DNA replication licensing is a prerequisite for, and plays a role in, regulating genome duplication that occurs exactly once per cell cycle. ORC (origin recognition complex) binds to and marks replication origins throughout the cell cycle and loads other replication-initiation proteins onto replication origins to form pre-replicative complexes (pre-RCs), completing replication licensing. However, how an asymmetric single-heterohexameric ORC structure loads the symmetric MCM (minichromosome maintenance) double hexamers is controversial, and importantly, it remains unknown when and how ORC proteins associate with the newly replicated origins to protect them from invasion by histones. Here, we report an essential and cell-cycle-dependent ORC "dimerization cycle" that plays three fundamental roles in the regulation of DNA replication: providing a symmetric platform to load the symmetric pre-RCs, marking and protecting the nascent sister replication origins for the next licensing, and playing a crucial role to prevent origin re-licensing within the same cell cycle., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Increase in acetabular cup abduction in total hip arthroplasty (THA) using conventional polyethylene is associated with greater linear wear. Whether this relationship holds true for highly crosslinked liners, particularly with long-term follow-up, is still controversial. The effect of liner thickness on wear of highly cross-linked liners also remains to be clarified.This study sought to determine (1) the long-term clinical and radiological performance of highly cross-linked polyethylene in THA and (2) the effect of acetabular component positioning, polyethylene thickness, and patient demographics on wear., Methods: Ninety-three THAs using a 28-mm hip ball, single brand of highly cross-linked polyethylene liner, and cementless cup were performed in 87 patients. Clinical outcomes were evaluated using the Harris Hip Score and need for revision surgery. Linear and volumetric wear, presence of osteolysis, and cup abduction angle were assessed., Results: The mean age at operation was 51.4 years. The mean duration of follow-up was 12.7 years (10-16 years). Patients aged >50 years had higher rates of linear wear than those aged <50 years (P = .015). Positive correlation was found between cup abduction angle (P = .014) and cup version (P = .035) with a linear wear rate. Thinner liners (≤7 mm) had similar rates of linear and volumetric wear as thicker liners (≥8 mm) (P = .447)., Conclusion: This is the only study to demonstrate a positive significant relationship between cup abduction angle and version with linear wear rate in THA with at least 10 years of follow-up. Liner thickness was not found to affect wear rates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Osteoarthritis (OA) of the knee is a growing problem in an aging population. Unicompartmental knee arthroplasties (UKA) have been used for management of isolated OA of the medial tibiofemoral joint. This is the first study on the usage of UKA in Hong Kong., Methods: Retrospective analysis of all patients undergoing medial compartment UKA in a tertiary referral center since 2003. Preoperative and postoperative International Knee Society Knee Scores (KSKS) and Knee Societal Functional Assessment (KSFA) scores, range of motion, flexion deformity, and lower limb mechanical alignment were measured. Statistical analysis using paired sample t-tests was performed. Revision operations, rate of revisions, and causes of failure were analyzed. Univariate and multivariate logistic regression analyses of risk factors for revision operation were performed against patient demographics, type of prosthesis, postoperative alignment, and degree of correction., Results: There were 94 UKA performed with an average follow-up of 4.3 years (range: 0.5-15.2 years). The KSKS and KSFA scores improved from 54.5 and 54.0 to 85.6 and 64.5 ( p < 0.01), respectively. There was no significant improvement in the range of motion ( p = 0.87) and fixed flexion deformity ( p = 0.14). Mechanical alignment improved from 172.1° to 174.9° varus postoperatively ( p < 0.01). Six cases required revision operation with a revision rate of 1.50 per 100 observed component years. Causes of revision included two cases of tibial tray loosening and one case each of progressive OA, mechanical failure, persistent pain, and infection. Logistic regression analysis for risk factors showed no statistical significance., Conclusions: UKA offers good functional improvement but further long-term studies are required to evaluate survivorship.

Noc3p (Nucleolar Complex-associated protein) is an essential protein in budding yeast DNA replication licensing. Noc3p mediates the loading of Cdc6p and MCM proteins onto replication origins during the M-to-G 1 transition by interacting with ORC (Origin Recognition Complex) and MCM (Minichromosome Maintenance) proteins. FAD24 (Factor for Adipocyte Differentiation, clone number 24), the human homolog of Noc3p (hNOC3), was previously reported to play roles in the regulation of DNA replication and proliferation in human cells. However, the role of hNOC3 in replication licensing was unclear. Here we report that hNOC3 physically interacts with multiple human pre-replicative complex (pre-RC) proteins and associates with known replication origins throughout the cell cycle. Moreover, knockdown of hNOC3 in HeLa cells abrogates the chromatin association of other pre-RC proteins including hCDC6 and hMCM, leading to DNA replication defects and eventual apoptosis in an abortive S-phase. In comparison, specific inhibition of the ribosome biogenesis pathway by preventing pre-rRNA synthesis, does not lead to any cell cycle or DNA replication defect or apoptosis in the same timeframe as the hNOC3 knockdown experiments. Our findings strongly suggest that hNOC3 plays an essential role in pre-RC formation and the initiation of DNA replication independent of its potential role in ribosome biogenesis in human cells.

Introduction: Intravenous infusion of lignocaine has emerged in recent years as a feasible, cost-effective, and safe method to provide postoperative analgesia. There is, however, no literature about this perioperative pain control modality in Chinese patients. This study aimed to determine whether perioperative intravenous lignocaine safely reduces postoperative pain, shortens postoperative ileus, and reduces the length of hospital stay in laparoscopic colorectal surgery., Methods: Between September 2012 and May 2015, 16 patients who underwent elective laparoscopic resection of colorectal cancer and received a 1% lignocaine infusion for 24 hours postoperatively were studied. After surgery, categorical pain scores were obtained immediately, followed by hourly pain scores at rest. Pain scores at rest and with mobilisation, and patient satisfaction score were documented on postoperative day 1. Return of bowel function was measured by time of first flatus and bowel opening. The patient's rehabilitation was assessed by time taken to tolerate diet, full mobilisation, and length of hospital stay., Results: The median (interquartile range) self-reported pain scores at 2 hours and 6 hours after surgery were 1.5 (0-4) and 2 (0-3), respectively. The median pain scores at rest and mobilisation on postoperative day 1 were 1 (0-2.5) and 2 (2.5-5), respectively, with a median satisfaction score of 7.5 (7-9). The median times to first flatus and first bowel opening were 21 (18-35) hours and 3 (1-3) days, respectively. No patient had postoperative ileus. The median times to tolerating diet and mobilisation were 1 (1-1) day and 2 (2-3) days, respectively. The median postoperative stay was 6 (5-8) days., Conclusions: Intravenous lignocaine is a safe and effective postoperative analgesic in a Chinese population. It enhances the rehabilitation process for patients following laparoscopic resection of colorectal cancer.

Objectives: To review the clinical outcome of locally advanced rectal cancer treated with neoadjuvant chemoradiation followed by definitive surgery with or without adjuvant chemotherapy and to elucidate the prognostic factors for treatment outcome., Methods: This historical cohort study was conducted at a tertiary public hospital in Hong Kong. All patients who had undergone neoadjuvant chemoradiation for locally advanced rectal cancer in our department from November 2005 to October 2014 were recruited. Local recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival of patients were documented., Results: A total of 135 patients who had received neoadjuvant chemoradiation during the study period were reviewed. There were 130 patients who had completed neoadjuvant chemoradiation and surgery. The median follow-up time was 35.1 months. The 3- and 5-year local recurrence-free survival, distant metastasis-free survival, disease-free survival, as well as overall survival rates were 91.8% and 86.7%, 73.9% and 72.1%, 70.1% and 64.6%, as well as 86.5% and 68.4%, respectively. The rate of pathological complete response was 13.8%. The T and N downstaging rate was 49.2% and 63.1%, respectively. The rate of conversion from threatened circumferential resection margin to clearance of margin was 90.6%. Of the 42 cases that were initially deemed to require abdominal perineal resection, 15 (35.7%) were converted to sphincter-sparing surgery., Conclusions: The treatment outcome of neoadjuvant chemoradiation for locally advanced rectal cancer was comparable with overseas data in terms of local control rate and overall survival. This strategy may increase the chance of achieving a clear surgical margin by downstaging the tumour, especially in patients who presented with threatened circumferential margin.

Chemical analysis of Chinese black ink on xuan paper is useful for the authentication of Asian artwork. The analysis has to be nondestructive and has to accommodate artworks of all sizes. We apply three analytical techniques, ArF laser-induced plume fluorescence, Fourier transform infrared (FTIR) spectroscopy, and portable X-ray fluorescence (pXRF) to analyze five commercial Chinese black inks on two kinds of xuan paper. The FTIR signal is found to be interfered by the substrate which is inevitable because the pigments diffuse extensively into the xuan fiber network. The XRF signal is shown to be feeble and no signal can be registered until the samples are stacked and when the analytes are present at tens of percent. In contrast, the plume fluorescence technique can detect the minor and trace signature elements. The method is based on a two-laser-pulse scheme performed on a high precision optical setup: the first 355 nm laser pulse ablates a thin layer of the ink to create a plume; the second 193 nm laser pulse induces multi analytes in the plume to fluoresce. Partial-least-squares discriminant analysis of the fluorescence spectra unambiguously sorts the ink-xuan combinations while the sampled area is not visibly damaged even under the microscope. The laser probe can handle samples of arbitrary size and shape, is air compatible, and no sample pretreatment is necessary.

Objective: Traditionally, fluoroscopy or ultrasound (US) or both are used for guiding tract creation during percutaneous nephrolithotomy (PCNL). However, the use of fluoroscopy inevitably incurs radiation exposure, which should be cut down as much as possible in view of its potential adverse effects on health: both deterministic effects and stochastic effects. Conventional US guidance, being radiation free, can serve the purpose, but it is difficult to visualize the needle tract during screening without a needle-guiding system fixed to the transducer, and hence, there is a lack of predictability and sense of security. The objective of this study is to assess the feasibility of using US with navigation system (USNS) to solve the above problems., Patients and Methods: In 2014, we performed PCNL on 18 patients with USNS guidance. During the puncture step, the magnetic field-based navigation US could help visualize the position of the needle tract in relation to the target calix. The procedure was done in free hand without the usage of needle-guiding system attached to the transducer. Needle deviation could be detected and adjusted immediately to achieve precise puncture., Results: Of the 18 patients, 83.3% (15/18) of them had their punctures effectively done with a single attempt. Three puncture procedures were performed by two urologic trainees without any previous USNS experience. The mean fluoroscopy time during dilatation was 74.6s, with no radiation at all during the puncture step. The stone clearance rate was 72.2%, with 66.7% (12/18) being tubeless procedures. The mean length of hospital stay was 4.8 days. No immediate complications related to the puncture procedure were found., Conclusions: USNS can provide radiation-free guidance for tract creation in PCNL. It is predictable, precise, reliable, and safe. Most importantly, the technique is easy to learn, particularly for urologists who are new to PCNL.

Background: In this prospective, randomized, double-blind, placebo-controlled trial, we tried to find out appropriate amounts of single-dose dexmedetomidine to prolong the duration of spinal anesthesia in a clinical setting., Methods: Sixty patients who were scheduled for unilateral lower limb surgery under spinal anesthesia were randomized into three groups receiving normal saline (control group, n = 20) or 0.5 or 1.0 ug/kg dexmedetomidine (D-0.5 group, n = 20; D-1, n = 20) intravenously prior to spinal anesthesia with 12 mg of bupivacaine. The two-dermatome pinprick sensory regression time, duration of the motor block, Ramsay sedation score (RSS), and side effects of dexmedetomidine were assessed., Results: The two-dermatome pinprick sensory regression time (57.6 ± 23.2 vs 86.5 ± 24.3 vs 92.5 ± 30.7, P = 0.0002) and duration of the motor block (98.8 ± 34.1 vs 132.9 ± 43.4 vs 130.4 ± 50.4, P = 0.0261) were significantly increased in the D-0.5 and D-1 groups than in the control group. The RSS were significantly higher in the D-0.5 and D-1 groups than in the control group. However, there were no patients with oxygen desaturation in dexmedetomidine groups. The incidences of hypotension and bradycardia showed no differences among the three groups., Conclusions: Both 0.5 and 1.0 ug/kg of dexmedetomidine administered as isolated boluses in the absence of maintenance infusions prolonged the duration of spinal anesthesia.

Objective: To compare the long-term reoperation rates among surgeons performing transatrial repair of tetralogy of Fallot., Methods: The data set of 675 patients undergoing transatrial repair of tetralogy of Fallot at 1 institution from 1980 to 2005 was analyzed for intersurgeon differences in the reoperation rates., Results: A follow-up period >15 years was available for 5 surgeons, allowing for comparison (541 patients; >80 patients/surgeon). The reintervention rate at 10 years varied from 8.8% (95% confidence interval [CI], 5.3%-14.5%) to 26.7% (95% CI, 14.9%-44.9%; hazard ratio, 3.4; P = .001). The procedures of 1 surgeon resulted in a reoperation rate of 10.5% at 20 years (95% CI, 5.4%-25.3%). The type of reoperation required varied among the surgeons. One surgeon had had no reoperations for pulmonary artery stenosis. Of the 5 surgeons, 2 (surgeons 2 and 5) had equivalent overall 10-year reoperation rates (24.1%, 95% CI, 12.9%-42.3%; vs 26.7%, 95% CI, 14.9%-44.9%; P = .32). Surgeon 5 had reoperation almost exclusively for right ventricular outflow tract obstruction (20.6%; 95% CI, 12.4%-33.1%) and surgeon 2 for right ventricular dilation (17.4%; 95% CI, 7.8%-36.3%). None of the patients treated by surgeon 5 required implantation of a valved conduit., Conclusions: An analysis of the reoperation rate during the long-term follow-up of transatrial repair of tetralogy of Fallot identified variability in the outcomes among 5 surgeons. The analysis of these differences suggested that an optimal amount of opening of the right ventricular outflow tract can lead to a decreased reintervention rate. The analysis of intersurgeon variability in outcomes should be encouraged, because it will lead to improvements in cardiac surgery outcomes., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: The study sought to evaluate the late outcomes of a policy of transatrial repair delayed beyond the neonatal period., Background: Long-term outcomes of transatrial repair of tetralogy of Fallot are unknown., Methods: The records of 675 consecutive patients undergoing a transatrial repair of tetralogy of Fallot between 1980 and 2005 were reviewed, their follow-up updated and survival confirmed from national death registries. One-third (220 of 675) had undergone previous palliation. Median age at repair was 2 years in the first 8 years, and 1 year from 1988 onward. A transannular incision was performed in 75% of cases and autologous pericardium was the material used to patch this incision in 92% of cases., Results: There were 7 hospital deaths (1%). Eight patients died during follow-up (2 sudden unexpected and 6 noncardiac deaths). Mean follow-up was 11.7 ± 6.3 years. Twenty-five years' survival was 97% (95% confidence interval [CI]: 95% to 98%). Twenty-five years' freedom from implantation of a valved conduit was 84.6% (95% CI: 77.8% to 89.5%). By multivariable analysis, prior palliation and younger age at repair were predictive of implantation of a valved conduit (hazard ratio: 2.4, 95% CI: 1.3 to 4.6, p = 0.008; hazard ratio: 0.70, 95% CI: 0.50 to 0.96, p = 0.03, respectively)., Conclusions: During long-term follow-up, transatrial repair of tetralogy of Fallot was associated with a minimal risk of sudden death and low rate of reintervention for right ventricular dilation and residual outflow tract obstruction., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Small ubiquitin-like modifier (SUMO) belongs to the family of ubiquitin-like proteins (Ubls) that can be reversibly conjugated to target-specific lysines on substrate proteins. Although covalently sumoylated products are readily detectible in gel-based assays, there has been little progress toward the development of robust quantitative sumoylation assay formats for the evaluation of large compound libraries. In an effort to identify inhibitors of ubiquitin carrier protein 9 (Ubc9)-dependent sumoylation, a high-throughput fluorescence polarization assay was developed, which allows detection of Lys-1201 sumoylation, corresponding to the major site of functional sumoylation within the transcriptional repressor trichorhino-phalangeal syndrome type I protein (TRPS1). A minimal hexapeptide substrate peptide, TMR-VVK₁₂₀₁TEK, was used in this assay format to afford high-throughput screening of the GlaxoSmithKline diversity compound collection. A total of 728 hits were confirmed but no specific noncovalent inhibitors of Ubc9 dependent trans-sumoylation were found. However, several diaminopyrimidine compounds were identified as inhibitors in the assay with IC₅₀ values of 12.5 μM. These were further characterized to be competent substrates which were subject to sumoylation by SUMO-Ubc9 and which were competitive with the sumoylation of the TRPS1 peptide substrates.

Elderly people with osteoarthritis of the knee and postpartum women are at risk of insufficiency fractures of the proximal fibular or tibia. We report on an 82-year-old woman with valgus osteoarthritis of the knee who developed insufficiency fractures of the right proximal fibula and then the right proximal tibia. She underwent total knee arthroplasty using a long tibial stem and a tibial locking plate with the Less Invasive Stabilization System.

Background: Repair of total anomalous pulmonary venous drainage (TAPVD) in neonates remains a challenge. It is associated with a high mortality. We aimed at determining a method for risk stratification of this group of patients., Methods: From 1994 to 2008, 54 patients underwent simple TAPVD operations during the first month of life. Mean pulmonary arterial pressure (PAP), mean systemic arterial pressure (MAP), systolic blood pressure, diastolic blood pressure, central venous pressure, and left atrial pressure were recorded in 44 of the 54 patients for the first 36 hours postoperatively. The remaining 10 patients were excluded because data from invasive pressure monitoring were not available., Results: There were overall 8 deaths (18.2%, 8/44), including 4 (9%, 4/44) early deaths, and 5 reoperations (11.4%, 5/44). The mean PAP was 23.1 ± 6.4 mm Hg, the mean MAP was 50.3 ± 5 mm Hg, and the PAP-to MAP-ratio (PAP/MAP) was 0.80 ± 0.36. By multivariable logistic analysis, the risk factors for mortality were a higher PAP/MAP (p = 0.037) and lower operative weight (p = 0.02). All deaths had either a PAP/MAP of greater than 0.80 or an operative weight of less than 2.5 kg. Hemodynamic index (PAP/MAP divided by operative weight) was predictive of mortality (p = 0.007). Furthermore, the hemodynamic index (p = 0.003) predicted prolonged length of stay in the intensive care unit by regression analysis., Conclusions: The hemodynamic index (PAP/MAP/weight) ≥0.25 in the first 36 hours after TAPVD repair in neonates is predictive of mortality. A higher index predicted longer stay in the intensive care unit. This hemodynamic index may be a useful adjunct for risk stratification in neonates undergoing TAPVD repair., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The differential diagnosis of heel pain is extensive. The plantar heel pain is usually due to mechanical etiology, including plantar fasciitis, calcaneal spur, stress fracture, and nerve entrapment. Tumor is a rare cause of plantar heel pain. We present a case of chronic plantar heel pain with a vascular leiomyoma at the heel pad.