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Background Given the complexity of living donor hepatectomy, it is expected that high hospital volume will better outcomes. This study aims to evaluate post-operative outcomes for living donor hepatectomy in a medium volume liver transplant centre and compare to outcomes in high volume centres. Also, it serves as a validation tool for framework of structure-process-outcome model for safe living donor hepatectomy program. Methods 204 donors who underwent donor hepatectomy between June 1996 to September 2019 were reviewed retrospectively and compared to outcomes in high volume centres. Results At 6 months, overall donor morbidity rate was 20/204 (9.8%). Wound complications were most common at 5/204 (2.5%). Majority of complications were either Clavien grade 1 or 2 and only 3 donors had Clavien grade 3 complications. There was zero donor mortality. Discussion Our centre's donor morbidity rate of 9.8% is the one of the lowest reported in the published literature. With increased experience, stringent donor selection and enhanced perioperative care by a multi-disciplinary team, outcomes in a medium volume centre can match the outcomes reported in high volume centres. The framework for quality in terms of structure, process and outcomes is presented which can be adopted for developing programs.

Aims To evaluate whether biomarkers derived from fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed prior to (prePET) and during the third week (interim PET; iPET) of radiotherapy can predict treatment outcomes in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPC). Materials and methods This retrospective analysis included 46 patients with newly diagnosed OPC treated with definitive (chemo)radiation and all patients had confirmed positive HPV status (HPV+OPC) based on p16 immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary, index node (node with the highest TLG) and total lymph nodes and their median percentage (≥50%) reductions in iPET were analysed, and correlated with 5-year Kaplan–Meier and multivariable analyses (smoking, T4, N2b-3 and AJCC stage IV), including local failure-free survival, regional failure-free survival, locoregional failure-free survival (LRFFS), distant metastatic failure-free survival (DMFFS), disease-free survival (DFS) and overall survival. Results There was no association of outcomes with prePET parameters observed on multivariate analysis. A complete metabolic response of primary tumour was seen in 13 patients; the negative predictive value for local failure was 100%. More than a 50% reduction in total nodal MTV provided the best predictor of outcomes, including LRFFS (88% versus 47.1%, P = 0.006, hazard ratio = 0.153) and DFS (78.2% versus 41.2%, P = 0.01, hazard ratio = 0.234). More than a 50% reduction in index node TLG was inversely related to DMFFS: a better nodal response was associated with a higher incidence of distant metastatic failure (66.7% versus 100%, P = 0.009, hazard ratio = 3.0). Conclusion The reduction (≥50%) of volumetric nodal metabolic burden can potentially identify a subgroup of HPV+OPC patients at low risk of locoregional failure but inversely at higher risk of distant metastatic failure and may have a role in individualised adaptive radiotherapy and systemic therapy.

PURPOSE The ideal location for mesh placement in minimally invasive ventral hernia repair (VHR) is still up for debate. We undertook a systematic review and meta-analysis (SRMA) to evaluate the outcomes of patients who received intraperitoneal mesh versus those that received extraperitoneal mesh in minimally invasive VHR. METHODS We searched PubMed, EMBASE, Cochrane, and Scopus from inception to May 3, 2021. We selected studies comparing intraperitoneal mesh versus extraperitoneal mesh placement in minimally invasive VHR. A meta-analysis was done for the outcomes of surgical site infection (SSI), seroma, hematoma, readmission, and recurrence. A subgroup analysis was conducted for a subset of studies comparing patients who have undergone intraperitoneal onlay mesh (IPOM) versus extended totally extraperitoneal approach (e-TEP). RESULTS A total of 11 studies (2320 patients) were identified. We found no statistically significant difference between patients who received intraperitoneal versus extraperitoneal mesh for outcomes of SSI, seroma, hematoma, readmission, and recurrence [(RR 1.60, 95% CI 0.60-4.27), (RR 1.39, 95% CI 0.68-2.81), (RR 1.29, 95% CI 0.45-3.72), (RR 1.40, 95% CI 0.69-2.86), and (RR 1.22, 95% CI 0.22-6.63), respectively]. The subgroup analysis had findings similar to the overall analysis. CONCLUSION Based on short-term results, extraperitoneal mesh does not appear to be superior to intraperitoneal mesh in minimally invasive ventral hernia repair. The choice of mesh location should be based on the current evidence, surgeon, and center experience as well as individualized to each patient.

When ethanol and water are mixed into gasoline, the dielectric properties of gasoline will change. Based on this characteristic, we propose an antenna sensor and study its radiation and sensing performance in detection of ethanol gasoline in 6-7GHz band. In order to avoid the corrosion of the oil sample on the antenna, the antenna adopts a multilayer dielectric substrate structure. A $2\times 2$ artificial magnetic conductor (AMC) array is loaded on the bottom of the antenna to increase the gain of the sensor and reduce the return loss. The antenna sensor has good radiation pattern with a peak gain of 4 dB and high quality factor(Q) up to 69. Furthermore, the antenna sensor shows the advantages of high sensitivity and wide detection range on the detection of oil-water mixture and ethanol gasoline concentration. In order to verify the simulated results, the radiation and sensing performance of the antenna were measured, and the measured results were basically consistent with the simulated ones. Therefore, the proposed antenna sensor can be used for real-time wireless detection in ethanol gasoline transportation.

There has not been a consensus on the superiority of a surgical approach for minimally invasive ventral hernia repair. This systematic review and meta-analysis (SRMA) aims to compare clinical, and patient-reported outcomes of robotic-assisted ventral hernia repair (rVHR) to traditional endo-laparoscopic ventral hernia repair (lapVHR). We searched PubMed, EMBASE, Cochrane and Scopus from inception to 16th March 2021. We selected randomised controlled trials and propensity score matched studies comparing rVHR to lapVHR. A meta-analysis was done for the outcomes of operative time, length of hospital stay, open conversion, recurrence, surgical site occurrence and cost. A total of 5 studies (3732 patients) were included in the qualitative and quantitative synthesis. Significantly shorter operative times were reported with the lapVHR as compared to rVHR (weighted mean difference (WMD): 62.52, 95% CI: 50.84–74.19). There was also significantly less rates of open conversion with rVHR as compared to lapVHR (WMD: 0.22, 95% CI: 0.09–0.54). No significant differences in patient-reported outcomes that was discernible from the two papers that reported them. Overall, rVHR is comparable to lapVHR with longer operative times but less open conversion. It is, therefore, important to have proper patient selection to maximise the utility of rVHR.

Background The potential protective role of eosinophils in the COVID-19 pandemic has aroused great interest, given their potential virus clearance function and the infection resistance of asthma patients to this coronavirus. However, it is unknown whether eosinophil counts could serve as a predictor of the severity of COVID-19. Methods A total of 1004 patients with confirmed COVID-19 who were admitted to Leishenshan Hospital in Wuhan, China, were enrolled in this study, including 905 patients in the general ward and 99 patients in the intensive care unit (ICU). We reviewed their medical data to analyze the association between eosinophils and ICU admission and death. Results Of our 1004 patients with COVID-19, low eosinophil counts/ratios were observed in severe cases. After adjusting for confounders that could have affected the outcome, we found that eosinophil counts might not be a predictor of ICU admission. In 99 ICU patients, 58 of whom survived and 41 of whom died, low eosinophil level was an indicator of death in severe COVID-19 patients with a cutoff value of 0.04 × 109/L, which had an area under the curve of 0.665 (95% CI = 1.089-17.839; P = .045) with sensitivity and specificity of 0.569 and 0.7317, respectively. Conclusion Our research revealed that a low eosinophil level is a predictor of death in ICU patients rather than a cause of ICU admission.

Objective To determine whether the purchase of prescription opioids was lower among people randomized to inpatient rehabilitation (IR) compared with those discharged directly home following total knee arthroplasty (TKA). Method A secondary analysis of a previous clinical trial in which participants were randomized 3 to 5 days after -surgery to 10 days of IR and a home program or to a home program alone. The primary outcome for this secondary analysis was the purchase of opioid-based pain relief up to 10-weeks after surgery, which was captured via patient diaries. Between-group differences were analyzed using a χ2 test and relative risk (RR) (95% confidence interval [CI]). We report this outcome alongside the main outcomes observed at 10 weeks for the original study (6-minute walk test, index joint pain, and function) for context. Results At 10 weeks, 158 participants were available for follow-up; 120 (76%) provided diaries, with 113 providing generic or brand names for the pain relief purchased. In the IR group, 60% (33/55) reported the purchase of opioid-based medications after discharge compared with 34% (20/58) in the home group (χ2 = 7.4; P = 0.007); thus, the risk of purchasing opioids for those in the IR group was almost double (RR, 1.7 [95% CI, 1.1-2.6]). No significant or meaningful between-group differences in index joint pain, function, or mobility were observed. Conclusion Contrary to what was hypothesized, IR is a strong driver of opioid purchase after discharge from the hospital following TKA.

Background Substantial studies have demonstrated that fasting therapy (FT) can inhibit the inflammatory response and improve insulin resistance (IR); however, the underlying mechanisms are still unclear. This study aimed to explore the related mechanisms of intermittent FT for the treatment of IR. Methods A rat IR model was established through collaboration of a high-fat diet with streptozotocin (STZ) injection. 8 rats were treated with intermittent FT. A positive control group was treated with metformin (MET). Mouse 3T3-L1 pre-adipocytes were cultured and induced into adipocytes in vitro, and were used as the cellular IR model. Blood insulin, glucose, and homeostatic model assessment (HOMA)-IR index were determined. Enzyme-linked immunosorbent assay (ELISA) and western blotting were used to detect inflammatory markers. Oil Red O staining determined the lipid accumulation. An NLRP3 inflammasome agonist served to investigate the effects of FT on IR in 3T3-L1 adipocytes. Results The high levels of blood insulin, glucose, and HOMA-IR induced by high-fat diet and STZ were significantly decreased by FT. The FT also reduced the level of C-reactive protein (CRP), interleukin (IL)-1β, IL-18, caspase-1, and increased the expression of glucose transporter 1 (GLUT1), insulin receptor substrate 1 (IRS1), and IRS2 in both the rat models and 3T3-L1 adipocytes. In addition, FT significantly relieved lipid accumulation in the liver of rats. Application of NLRP3 inflammasome agonist weakened the effect of FT on IR in the IR 3T3-L1 adipocytes. Conclusions These results suggest that FT can ameliorate the high-fat diet-and STZ-induced IR in rats through inhibition of NLRP3 inflammasome.

Background Therapeutic drug monitoring (TDM) of infliximab (IFX) levels in inflammatory bowel disease (IBD) patients can help to guide dose adjustments or changes to therapy for selected patients in remission or with secondary loss of response (LOR). Aims To determine how IFX TDM is utilised in a real-life clinical setting and to quantify the potential for TDM to reduce the unnecessary use of IFX. Methods Data from all public IBD IFX level testing performed across Australia were prospectively collected from June 2016 to July 2017 to assess physician-reported for testing indications (induction, in remission or LOR) and associated results. The hypothetical influence of IFX TDM was based on an optimal therapeutic range of 6-10 mg/L for mucosal healing. Results Secondary LOR (reactive TDM) was the most common indication for TDM. These patients have consistently lower median IFX levels: 3.02 mg/L (IQR 1.14-6.67 mg/L) versus 5.22 mg/L (IQR 2.70-8.12 mg/L), P = 0.0001 compared with patients in remission (proactive TDM). TDM helped to identify unnecessary use of IFX in 30.6% of the TDM tests performed in luminal Crohn disease and ulcerative colitis patients, with an associated drug cost saving of $531.38 per IFX TDM test episode. Unnecessary IFX use was identified in 38.9% (96/247) of reactive IFX TDM tests performed and in 19.3% (35/181) of proactive testing. Conclusion Use of both reactive and proactive IFX TDM is cost-effective for IBD management as it informs the clinician where unnecessary use of IFX can be stopped.

MTE Mechanical Private Limited Company is a manufacturing company located at Batu Maung, Malaysia producing fabricated metal products. During 2020, the company’s revenue has significantly decreased compared to the previous year. Therefore, the purpose of this research is to identify the factors which affect the revenue of the company. Online interviews were used to collect information from the company’s owner and three of their customers. The present study found that the delivery service and product’s quality of the company are the major issues having effects upon the company’s revenue. Moreover, the findings of the present study would benefit the company.

Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses. Electronic supplementary material The online version of this article (10.1007/s10439-020-02683-x) contains supplementary material, which is available to authorized users.

Citrus fruit granulation is a major physical disorder during late maturity and post-harvest storage, and it greatly undermines the quality of fruit. Currently, there is still a lack of rapid and nondestructive methods to detect citrus granulation. This study proposes a nondestructive granulation detecting method based on deep learning. Different models were established with the input of preprocessed transmission spectra obtained by hyperspectral imaging. Conventional convolution neural network (CNN) got the best accuracy at 88.02% for training, compared with the least-square support vector machine (LS-SVM) and back-propagation neural network (BP-NN). After adding the batch-normalization layer to the CNN, the experimental results show that the detection model obtained a 100% accuracy in train set and 97.9% in validation set, respectively. And then, through analyzing the well-trained model layer by layer, bands of 660.2–721.1 nm, 708.5–750 nm and 806.5–847 nm were the spectra greatly related to granulation. The model rebuilt with these feature bands obtained 90.1% and 85.4% accuracy in train set and validation set, respectively. This way, effective wavelength selection can find bands highly correlated with granulation.Combined with some research on functional group, it is possible that inference to internal matter changes in granulation process, which may provide some hints to explore the reason of granulation. It is also meaningful to develop granulation-detecting equipment for citrus fruits.

Pancreatic cancer is one of the deadliest types of cancer and its prognosis is extremely poor in the present scenario. Automatic pancreatic tumor image segmentation is often provided by computer-aided screening (CAD), diagnosis and quantitative evaluations in radiology images such as CT and MRI. Tumor classification through these methods can also help to track, predict and endorse customized therapy as a part of effective treatment, without invasions of cancer. Nowadays, neural networks (NN) have shown promising results for precise pancreatic image segmentation. This paper presents a deep learning-based Hierarchical Convolutional Neural Network (HCNN) for pancreatic tumor detection. A recurrent neural network (RNN) is provided to meet the issue of spatial discrepancy segmentation across slices of adjacent images. The recurrent neural network generates CNN results and fine-tunes its segmentation by enhancing the smoothness and shape. Furthermore, the HCNN training and configurations objectives have been illustrated to the performance of pancreatic tumor image segmentation. The experimental results demonstrate that the proposed approach can improve the performance of the classifier and reduce the cost on the Internet of medical things platform (IoMT).

Background We are performing a combined randomised and observational study comparing internal fixation to non-surgical management for common wrist fractures in older patients. This paper describes the statistical analysis plan. Methods/design A Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly (CROSSFIRE) is a randomised controlled trial comparing two types of usual care for treating wrist fractures in older patients, surgical fixation using volar locking plates and non-surgical treatment using closed reduction and plaster immobilisation. The primary aim of this comparative-effectiveness study is to determine whether surgery is superior to non-surgical treatment with respect to patient-reported wrist function at 12 months post treatment. The secondary outcomes include radiographic outcomes, complication rates and patient-reported outcomes including quality of life, pain, treatment success and cosmesis. Primary analysis will use a two-sample t test and an intention-to-treat analysis using the randomised arm of the study. Statistical analyses will be two-tailed and significance will be determined by p Discussion This statistical analysis plan describes the analysis of the CROSSFIRE study which aims to provide evidence to aid clinical decision-making in the treatment of distal radius fractures in older patients. Trial registration CROSSFIRE was approved by The Hunter New England Human Research Ethics Committee (HNEHREC Reference No: 16/02/17/3.04). Registered on 22 July 2016 with The Australian and New Zealand Clinical Trials Registry (ANZCTR Number; ACTRN12616000969460). This manuscript is based on v.11 of the statistical analysis plan. A copy of v.11, signed by the chief investigator and the senior statistician is kept at the administering institution.

Passenger flow is the basis for bus operation scheduling. Huge advances are being made to develop smart city traffic using big data. Intelligent bus systems based on bus integrated circuit (IC) card systems are constantly developing and improving. Compared with traditional manual survey data, bus IC data is low-cost, real-time and accurate with a simple acquisition method. Bus IC data is an important basic data resource and data mining of bus IC cards can obtain dynamic information about urban bus passenger flow and help improve urban bus planning and service levels. The crucial factor in determining whether this data can be reasonably applied to the optimization of urban bus systems is whether spatial and temporal characteristics of the passenger bus trip can be obtained through bus IC data mining, and there is much current research interest into this topic. In this paper, the characteristics of one-day passenger flow and time-division passenger flow are analyzed based on data obtained from swiping IC cards for one week on a bus in Qingdao. Then, based on a GA-NARX neural network model, the passenger flow is forecast using the IC card swipe data for five working days of Qingdao No. 1 bus (using ten minutes as the time interval). The forecasting results show that the passenger flow can be successfully predicted using this method and thus this method can be used for short-term passenger flow forecasting using bus IC cards.

Congenital heart malformations occur to substantial number of pregnancies. Studies showed that abnormal flow biomechanical environments could lead to malformations, making it important to understand the biomechanical environment of the developing heart. We performed 4D high-frequency ultrasound scans of chick embryonic hearts at HH25 to study the biomechanics of the whole heart (atria and ventricle). A novel and high-fidelity motion estimation technique, based on temporal motion model and non-rigid image registration algorithm, allowed automatic tracking of fluid-structure boundaries from scan images, and supported flow simulations. Results demonstrated that atrial appendages were the most contractile portion of the atria, having disproportionately high contribution to atrial blood pumping for its volume in the atria. However, the atria played a small role in blood pumping compared to the ventricle, as it had much lower ejection energy expenditure, and as the ventricle appeared to be able to draw inflow from the veins directly during late diastole. Spatially and temporally averaged wall shear stresses (WSS) for various cardiac structures were 0.062–0.068 Pa, but spatial-averaged WSS could be as high as 0.54 Pa in the RV. WSS was especially elevated at the atrial inlet, atrioventricular junction, regions near to the outflow tract, and at dividing lines between the left and right atrium and left and right side of the ventricle, where septation had begun and the lumen had narrowed. Elevated WSS could serve as biomechanics stimulation for proper growth and development.

Objective Delayed thrombolytic therapy with recombinant tissue plasminogen activator (tPA) may exacerbate blood‐brain barrier (BBB) breakdown after ischemic stroke and lead to catastrophic hemorrhagic transformation (HT). Rosiglitazone(RSG), a widely used antidiabetic drug that activates peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), has been shown to protect against cerebral ischemia through promoting poststroke microglial polarization toward the beneficial anti‐inflammatory phenotype. However, whether RSG can alleviate HT after delayed tPA treatment remains unknown. In this study, we sort to examine the role of RSG on tPA‐induced HT after stroke. Methods and results We used the murine suture middle cerebral artery occlusion (MCAO) models of stroke followed by delayed administration of tPA (10 mg/kg, 2 hours after suture occlusion) to investigate the therapeutic potential of RSG against tPA‐induced HT. When RSG(6 mg/kg) was intraperitoneally administered 1 hour before MCAO in tPA‐treated MCAO mice, HT in the ischemic territory was significantly attenuated 1 day after stroke. In the tPA‐treated MCAO mice, we found RSG significantly mitigated BBB disruption and hemorrhage development compared to tPA‐alone‐treated stroke mice. Using flow cytometry and immunostaining, we confirmed that the expression of CD206 was significantly upregulated while the expression of iNOS was down‐regulated in microglia of the RSG‐treated mice. We further found that the expression of Arg‐1 was also upregulated in those tPA and RSG‐treated stroke mice and the protection against tPA‐induced HT and BBB disruption in these mice were abolished in the presence of PPAR‐γ antagonist GW9662 (4 mg/kg, 1 hour before dMCAO through intraperitoneal injection). Conclusions RSG treatment protects against BBB damage and ameliorates HT in delayed tPA‐treated stroke mice by activating PPAR‐γ and favoring microglial polarization toward anti‐inflammatory phenotype.

The treatment of atypical femoral shaft fractures with abnormal bowing provides a unique challenge for surgeons. Whilst intramedullary fixation of atypical femoral shaft fractures affords both mechanical and biological benefits, the mismatch between standard intramedullary devices and the abnormal femoral bowing in these patients makes this method of fixation challenging for the surgeon. The purpose of this manuscript is to illustrate the evolution of our surgical technique through a series of four patients. The critical factors we identified include lateral positioning of the patient for reduction, the use of a piriformis-start nail, and an entry point that was anterior in the sagittal profile and lateral in the coronal profile. This technique was easily replicable, facilitated more anatomical reduction and aided in avoiding complications.

Background The volume-outcome relation for complex surgical procedures such as living donor liver transplantation (LDLT) generally favors high volume (HV) centers . It is important for low to medium volume (MV) centers to evaluate their centers’ performance against HV centers to allow early detection and correction of potential systemic issues. There is a dearth of national and international comprehensive registries for LDLT that may allow reasonable risk-adjusted comparisons for benchmarking. This study aims to evaluate the LDLT program by comparing our center's performance against HV centers of the Adult-to-Adult Living Donor Liver Transplantation cohort. Study design Patient outcomes from a MV transplant center were compared with 11 HV transplant centers from the Adult-to-Adult Living Donor Liver Transplantation cohort. Outcomes evaluated included length of hospital stay, same admission mortality, 90-day mortality, and overall survival. Results A total of 1381 patients were analzyed. HV 1 to 4, 6, 8, 9, and 11 centers had a shorter median length of hospital stay compared with the MV center (All Dunnett corrected P values all less than .05). HV 9 and 11 centers had lower same admission mortality compared with the MV center (Dunnett corrected P = .023 and .015). After adjusting for other significant predictors, the MV center had comparable 90-day mortality rates and overall survival rates to all HV centers. Conclusion This benchmarking exercise has demonstrated that the limitation of low institutional case volume can be overcome with a protocol-based framework to implement a safe LDLT program. This framework presented can be adopted for developing programs.

Background Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of liver cirrhosis. This study aims to analyze the prevalence of SBP among liver cirrhotic patients according to geographical location and income level, and risk factors and outcomes of SBP. Methods A systematic search for articles describing prevalence, risk factors and outcomes of SBP was conducted. A single-arm meta-analysis was performed using generalized linear mix model (GLMM) with Clopper-Pearson intervals. Results 99 articles, comprising a total of 5,861,142 individuals with cirrhosis were included (IDDF2021-ABS-0019 Figure 1. Summary of Findings). Pooled prevalence of SBP was found to be 17.12% globally (CI: 13.63% - 21.30%), highest in Africa (68.20%; CI: 12.17% - 97.08%), and lowest in North America (10.81%; CI: 5.32% - 20.73%; IDDF2021-ABS-0019 Figure 2. Summary of SBP prevalence by region). The summary of the global prevalence is found in figure 1. Prevalence of community-acquired SBP was 6.05% (CI: 4.32% - 8.40%), and 11.11% (CI: 5.84% - 20.11%,) for healthcare-associated SBP. Antibiotic-resistant microorganisms were found in 11.51% (CI: 7.28% - 17.74%) of SBP patients. Of which, methicillin-resistant Staphylococcus aureus was most common (6.23%; CI: 3.83% – 9.97%), followed by extended-spectrum beta-lactamase producing organisms (6.19%; CI: 3.32% - 11.26%), and lastly vancomycin-resistant enterococci (1.91%; CI: 0.41% - 8.46%). A subgroup analysis was conducted to compare the rate of resistant SBP based on continent and summarized in figure 2. Subgroup analysis comparing prevalence, antibiotic resistance and outcomes between income groups. Conclusions SBP remains a frequent complication of liver cirrhosis worldwide. The drawn link between income level and SBP in liver cirrhosis may enable further insight on actions necessary to tackle the disease on a global scale.

Background Endoscopic variceal ligation (EVL) is a common procedure for primary and secondary prevention of variceal bleeding in cirrhosis patients. As portal vein thrombosis is associated with a higher risk of variceal bleeding and decompensation in cirrhosis patients, anticoagulation may be considered in these patients. However, it is uncertain if continuing anticoagulation during EVL may significantly increase the risk of bleeding. To address this gap, we performed a systematic review and meta-analysis to evaluate the safety of continuing anticoagulation during EVL. The primary outcome was the bleeding risk following EVL. Secondary outcomes were mortality following EVL and length of stay (LOS). Methods We performed a systematic search of 4 electronic databases (PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrial.gov) up to May 21, 2021 using both free text and MeSH terms. We included all studies that reported the 4-week rebleeding rate in cirrhosis patients during EVL, regardless of study design, language, publication types or status. The pooled relative risk (RR), mean difference (MD) and 95% confidence interval (95%CI) of study outcomes were estimated using Review Manager in a random-effect model. Results A total of six studies (5,102 subjects, 1,028 received anticoagulation) fulfilled our inclusion criteria. The mean (standard deviation) MELD and Child-Pugh score were 18 (5.5) and 7 (1.6), respectively. Follow-up duration ranged from 6 to 196 weeks. The overall pooled risk of bleeding and mortality was 8.2% (95%CI: 6.6%-10.0%) and 8.6% (95%CI: 4.2%-15.3%), respectively. Mean number of bands deployed per session was similar between the anticoagulation and control group. Continuation of anticoagulants during EVL was not associated with a higher pooled risk of bleeding (RR: 0.90, 95%CI: 0.71-1.15, I2 =0%) and mortality (RR: 1.16, 95%CI: 0.22-6.19) following EVL. However, continuing anticoagulation was associated with a shorter LOS (3.9 days, 95%CI: -7.35 to -0.48 days, I2 =0%). All studies had a low risk of bias except for one. Conclusions In cirrhosis patients undergoing EVL, continuing anticoagulation was safe without a significant increase in bleeding and mortality.

Diabetic nephropathy (DN) is one of the most serious and major renal complications of diabetes. Previously, Six-transmembrane Protein of Prostate 2 (STAMP2) was reported to contribute to nutritional stress. The purpose of this study is to investigate whether overexpression of STAMP2 attenuates diabetic renal injuries in DN rats. We induced the DN rat model by high-fat diet and low-dose streptozotocin and evaluated the metabolite and urine albumin/creatinine. Recombinant adeno-associated virus vectors were injected for overexpression of STAMP2. Pathophysiologic and ultrastructure features of DN by histochemical stain and transmission electron microscope, autophagy-related proteins and signaling pathway by western blotting were assessed. We found the expression of STAMP2 was decreased and autophagy was blunted in DN rat kidneys. Overexpressing STAMP2 significantly ameliorated metabolic disturbance, insulin resistance, and specifically restoring diabetic renal injury. Furthermore, overexpressing STAMP2 improved the autophagy deficiency in DN rats, as revealed by changes in the expressions of Beclin1, p62, and LC3. Furthermore, STAMP2 overexpressing promoted autophagy by inhibiting the mTOR and activating the AMPK/SIRT1 signaling pathway. Our results suggested that STAMP2 overexpression attenuated renal injuries via upregulating autophagy in DN rats. STAMP2 overexpressing promoted autophagy may been involved with inhibition of the mTOR/ULK1 and activation of the AMPK/SIRT1 signaling pathway.

Partial label learning deals with training examples each associated with a set of candidate labels, among which only one is valid. Most existing works focus on manipulating the label space by estimating the labeling confidences of candidate labels, while the task of manipulating the feature space by dimensionality reduction has been rarely investigated. In this paper, a novel partial label dimensionality reduction approach named CENDA is proposed via confidence-based dependence maximization. Specifically, CENDA adapts the Hilbert-Schmidt Independence Criterion (HSIC) to help identify the projection matrix, where the dependence between projected feature information and confidence-based labeling information is maximized iteratively. In each iteration, the projection matrix admits closed-form solution by solving a tailored generalized eigenvalue problem, while the labeling confidences of candidate labels are updated by conducting kNN aggregation in the projected feature space. Extensive experiments over a broad range of benchmark data sets show that the predictive performance of well-established partial label learning algorithms can be significantly improved by coupling with the proposed dimensionality reduction approach.

Background and Aims: Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of liver cirrhosis. This study aims to analyze the prevalence of SBP among liver cirrhotic patients according to geographical location and income level, and risk factors and outcomes of SBP.Methods: A systematic search for articles describing prevalence, risk factors and outcomes of SBP was conducted. A single-arm meta-analysis was performed using generalized linear mix model (GLMM) with Clopper-Pearson intervals.Results: Ninety-Nine articles, comprising a total of 5,861,142 individuals with cirrhosis were included. Pooled prevalence of SBP was found to be 17.12% globally (CI: 13.63–21.30%), highest in Africa (68.20%; CI: 12.17–97.08%), and lowest in North America (10.81%; CI: 5.32–20.73%). Prevalence of community-acquired SBP was 6.05% (CI: 4.32–8.40%), and 11.11% (CI: 5.84–20.11%,) for healthcare-associated SBP. Antibiotic-resistant microorganisms were found in 11.77% (CI: 7.63–17.73%) of SBP patients. Of which, methicillin-resistant Staphylococcus aureus was most common (6.23%; CI: 3.83–9.97%), followed by extended-spectrum beta-lactamase producing organisms (6.19%; CI: 3.32–11.26%), and lastly vancomycin-resistant enterococci (1.91%; CI: 0.41–8.46%). Subgroup analysis comparing prevalence, antibiotic resistance, and outcomes between income groups was conducted to explore a link between socioeconomic status and SBP, which revealed decreased risk of SBP and negative outcomes in high-income countries.Conclusion: SBP remains a frequent complication of liver cirrhosis worldwide. The drawn link between income level and SBP in liver cirrhosis may enable further insight on actions necessary to tackle the disease on a global scale.

Background There is controversy about the proactive clinical application of therapeutic drug monitoring (TDM) of biologic drugs in Crohn’s disease (CD). One way to practically assess this is to examine how TDM influences management decisions. We examined how knowledge of proactive and reactive antitumor necrosis factor (anti-TNF) drug levels changes management in a variety of clinical scenarios. Methods In this retrospective cohort study, all adults with CD having trough level infliximab or adalimumab measurements at Liverpool Hospital between June 2013 and July 2016 were included. Demographics, indications for testing, anti-TNF drug levels, and treatment details were collected along with subsequent management decisions. The decision made by the treating clinician after receiving the drug level was compared to a consensus decision from a panel of 3 gastroenterologists based on the clinical, laboratory, imaging, and/or endoscopic results without the drug level. When these 2 decisions were discrepant, the anti-TNF drug level was deemed to have changed management. Results One hundred and eighty-seven trough levels of infliximab or adalimumab from 108 patients were analyzed. Overall, assessment of anti-TNF levels affected management in 46.9% of the instances. Knowledge of the drug level was also more likely to result in management change when the test was performed for reactive TDM compared to proactive TDM (63% vs 36%, P = .001). Conclusions The addition of TDM of anti-TNF agents to routine investigations alters management decisions in adult CD patients on anti-TNF therapy in both proactive and reactive settings.

Background Ejection Fraction (EF) has been an important parameter describing cardiac function, because of earlier work demonstrating its correlation with outcomes. However, during conditions such as Heart Failure preserved ejection fraction (HFpEF), EF fails to distinguish HFpEF from healthy patients. There are further reports that EF can be skewed by the geometry of the heart, and Heart Failure (HF) can present a wide variety of cardiac morphologies due to remodelling. The reason for the poor performance of EF and its dependency on geometry is unclear, and it is further unclear if such geometric changes from HF remodelling affects cardiac function. We strive to address this here, and derive an improve and simple EF parameter to resolve this. Methods We developed a simple discretized numerical model to relate incompressible myocardial strains to stroke volume. We used data from two porcine animal models of heart failure, one for HFpEF and one for HF reduced EF (HFrEF), and literature clinical measurements to inform our model. We used the model to test the effects of geometric changes relevant to HF on the ability of the heart to convert myocardial strains to flow function. Results Our animal models showed that cardiac dilation and wall thickening are primary features relevant to HF. Further investigation via our numerical model showed that wall thickening with no change to strain artificially increased EF, while cardiac dilation with no change to strain artificially decreased EF, demonstrating that EF can be skewed by geometric changes during HF remodelling, and is an inaccurate representation of cardiac function. We further showed that this is because EF is calculated using the endocardial boundary rather than the mid-wall layer, because a corrected EF parameter (CEF) that uses the mid-wall layer for quantification resolves this shortcoming. This CEF became independent of cardiac geometry, and could successfully distinguish HFpEF and healthy heart in our animal models, where EF could not. The CEF can be calculated easily with measurements of EF, wall thickness, and LV inner diameter. We further showed that the myocardial strains at the endocardial and epicardial boundary deviated significantly from each other and from the strains at the mid-wall layer, and this magnitude of deviation depended on the cardiac geometry, suggesting that any quantification of cardiac function using the epi- or endo- boundaries can be skewed by geometric changes to the heart, and will be ineffective. Finally, we tested specific types of HF morphologies, namely, eccentric hypertrophy, concentric hypertrophy, and concentric remodelling with our numerical model. We found that the concentric remodelling morphology is the most inefficient in converting myocardial strains to stroke volume, while eccentric hypertrophy is the most efficient. This may explain why HFpEF hearts, which are likely have wall thickening similar to concentric remodelling, have exercise intolerant, and our results suggest that cardiac dilation during HFrEF is providing advantages to help with flow function. Conclusion We demonstrated that geometric changes during HF remodeling can significantly impact cardiac function, and can skews functional parameters like EF. We further showed that the reason for EF’s shortcoming is due to a flawed reliance on quantification using the endocardial boundary of the heart rather than the mid-wall layer. We proposed a new CEF parameter to replace EF that can resolve the shortcoming, and that can distinguish HFpEF from healthy hearts. Conflict of Interest None to declare

In this article we proclaim excellent improvement in the defect densities in hafnium zirconium oxide based ferroelectric film obtained by extending the duration of post-metallization annealing up to 180s. The consequences of extending the annealing duration on the structure and surface morphology was gauged by XRD analysis, HR-TEM and AFM, which showed increase in the grain size, well defined crystallinity, lower defect densities and negligible impact on surface roughness. The electrical characterization revealed reduction in RC leakage along with a significant improvement in flicker noise and random telegraphic noise characteristics, which proves reduction of defect densities when the annealing time is increased.

Background 4D ultrasound images of human fetal heart are important for medical applications such as evaluation of fetal heart function and early diagnosis of congenital heart diseases. However, due to the high noise and low contrast characteristics in fetal ultrasound images, denoising and enhancements are important. Methods In this paper, a special method framework for denoising and enhancing is proposed. It consists of a 4D-NLM (non-local means) denoising method for 4D fetal heart ultrasound image sequence, which takes advantage of context similar information in neighboring images to denoise the target image, and an enhancing method called the Adaptive Clipping for Each Histogram Pillar (ACEHP), which is designed to enhance myocardial spaces to distinguish them from blood spaces. Results Denoising and enhancing experiments show that 4D-NLM method has better denoising effect than several classical and state-of-the-art methods such as NLM and WNNM. Similarly, ACEHP method can keep noise level low while enhancing myocardial regions better than several classical and state-of-the-art methods such as CLAHE and SVDDWT. Furthermore, in the volume rendering after the combined "4D-NLM+ACEHP" processing, the cardiac lumen is clear and the boundary is neat. The Entropy value that can be achieved by our method framework (4D-NLM+ACEHP) is 4.84. Conclusions Our new framework can thus provide important improvements to clinical fetal heart ultrasound images.

Left atrial ligation (LAL) of the chick embryonic heart at HH21 is a model of the hypoplastic left heart syndrome (HLHS) disease, demonstrating morphological and hemodynamic features similar to human HLHS cases. Since it relies on mechanical intervention without genetic or pharmacological manipulations, it is a good model for understanding the biomechanics origins of such HLHS malformations. To date, however, the fluid mechanical environment of this model is poorly understood. In the current study, we performed 4D ultrasound imaging of LAL and normal chick embryonic hearts and 4D cardiac flow simulations to help shed light on the mechanical environment that may lead to the HLHS morphology. Results showed that the HH25 LAL atrial function was compromised, and velocities in the ventricle were reduced. The HH25 LAL ventricles developed a more triangular shape with a sharper apex, and in some cases, the atrioventricular junction shifted medially. These changes led to more sluggish flow near the ventricular free wall and apex, where more fluid particles moved in an oscillatory manner with the motion of the ventricular wall, while slowly being washed out, resulting in lower wall shear stresses and higher oscillatory indices. Consequent to these flow conditions, at HH28, even before septation is complete, the left ventricle was found to be hypoplastic while the right ventricle was found to be larger in compensation. Our results suggest that the low and oscillatory flow near the left side of the heart may play a role in causing the HLHS morphology in the LAL model. Supplementary Information The online version contains supplementary material available at 10.1007/s10237-021-01447-3.

About 10 million people in China are infected with hepatitis C virus (HCV), with the seroprevalence of anti-HCV in the general population estimated at 0.6%. Delaying effective treatment of chronic hepatitis C (CHC) is associated with liver disease progression, cirrhosis, hepatocellular carcinoma, and liver-related mortality. The extrahepatic manifestations of CHC further add to the disease burden of patients. Managing CHC-related advanced liver diseases and systemic manifestations are costly for both the healthcare system and society. Loss of work productivity due to reduced well-being and quality of life in CHC patients further compounds the economic burden of the disease. Traditionally, pegylated-interferon plus ribavirin (PR) was the standard of care. However, a substantial number of patients are ineligible for PR treatment, and only 40%-75% achieved sustained virologic response. Furthermore, PR is associated with impairment of patient-reported outcomes (PROs), high rates of adverse events, and poor adherence. With the advent of direct acting antivirals (DAAs), the treatment of CHC patients has been revolutionized. DAAs have broader eligible patient populations, higher efficacy, better PRO profiles, fewer adverse events, and better adherence rates, thereby making it possible to cure a large proportion of all CHC patients. This article aims to provide a comprehensive evaluation on the value of effective, curative hepatitis C treatment from the clinical, economic, societal, and patient experience perspectives, with a focus on recent data from China, supplemented with other Asian and international experiences where China data are not available.

Background Intercostal chest catheter (ICC) insertion is a common hospital procedure with attendant risks including life‐threatening complications such as pneumothorax and visceral damage. Aim To investigate the effect of a quality improvement (QI) initiative on complications associated with inpatient thoracostomy tube insertion. Methods Following an audit of ICC complications in inpatients over a 2‐year period we implemented a comprehensive QI programme. This involved formal training in and mandatory use of thoracic ultrasound, standardisation of the procedure and documentation, a dedicated procedure room with nurses trained in assisting ICC insertion and senior supervision for medical staff. An audit over 2 years post‐implementation of the QI protocol was compared with pre‐implementation results. Results A total of 103 cases were reviewed pre‐implementation and 105 cases were reviewed post‐implementation of the QI programme. All procedures following the QI initiative were image guided compared to 23.3% of cases pre‐implementation. The rate of developing a pneumothorax requiring intervention post‐implementation was less than pre‐implementation (1.9% vs 5.8% (P = 0.023). Post‐implementation, there were no instances of dry taps, viscera perforation, clinically significant bleeding or wrong side ICC insertion and documentation improved. Conclusion QI initiative applied to thoracostomy tube insertion in hospital inpatients can reduce complications and improve procedure documentation.

Depression is increasingly recognized as an inflammatory disease, with inflammatory crosstalk in the brain contributing its pathogenesis. Life stresses may up-regulate inflammatory processes and promote depression. Although cytokines are central to stress-related immune responses, their contribution to stress-induced depression remains unclear. Here, we used unpredictable chronic mild stress (UCMS) to induce depression-like behaviors in mice, as assessed through a suite of behavioral tests. C-X-C motif chemokine ligand 1 (CXCL1)-related molecular networks responsible for depression-like behaviors were assessed through intrahippocampal microinjection of lenti-CXCL1, the antidepressant fluoxetine, the C-X-C motif chemokine receptor 2 (CXCR2) inhibitor SB265610, and the glycogen synthase kinase-3β (GSK3β) inhibitor AR-A014418. Modulation of apoptosis-related pathways and neuronal plasticity were assessed via quantification of cleaved caspase-3, B-cell lymphoma 2-associated X protein, cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) protein expression. CXCL1/CXCL2 expression was correlated with depression-like behaviors in response to chronic stress or antidepressant treatment in the UCMS depression model. Intrahippocampal microinjection of lenti-CXCL1 increased depression-like behaviors, activated GSK3β, increased apoptosis pathways, suppressed CREB activation, and decreased BDNF. Administration of the selective GSK3β inhibitor AR-A014418 abolished the effects of lenti-CXCL1, and the CXCR2 inhibitor SB265610 prevented chronic stress-induced depression-like behaviors, inhibited GSK3β activity, blocked apoptosis pathways, and restored BDNF expression. The CXCL1/CXCR2 axis appears to play a critical role in stress-induced depression, and CXCR2 is a potential novel therapeutic target for patients with depression.-Chai, H.-H., Fu, X.-C., Ma, L., Sun, H.-T., Chen, G.-Z., Song, M.-Y., Chen, W.-X., Chen, Y.-S., Tan, M.-X., Guo, Y.-W., Li, S.-P. The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.

Objectives There is an increased interest in enhanced recovery after surgery (ERAS) minimizing adverse events after orthopedic surgery. Little consensus supports the effectiveness of these interventions. The purpose of present systematic review and meta-analysis is to comprehensively analyze and evaluate the significance of ERAS interventions for postoperative outcomes after orthopedic surgery. Methods PubMed, EMBASE, and Cochrane databases were totally searched from the inception dates to May 31, 2018. Two reviewers independently extracted the data from the selected articles using a standardized form and assessed the risk of bias. The analysis was performed using STATA 12.0. Results A total of 15 published studies fulfilled the requirements of inclusion criteria. We found that the ERAS group showed a significant association with lower incidence of postoperative complications (OR, 0.70; 95% CI, 0.64 to 0.78). Meanwhile, ERAS was also associated with the decline in 30-day mortality rate and Oswestry Disability Index (ODI). However, no significant differences were identified between the two groups regarding the 30-day readmission rate (P = 0.397). Conclusions Our meta-analysis suggested that the ERAS group had more advantages in reducing incidence of postoperative complications, 30-day mortality rate, and ODI after orthopedic surgery, but not of 30-day readmission rate. However, further research with standardized, unbiased methods and larger sample sizes is required for deeper analysis. Electronic supplementary material The online version of this article (10.1186/s13018-019-1116-y) contains supplementary material, which is available to authorized users.

Stroke is the world's leading cause of disability with limited brain repair treatments which effectively improve long‐term neurological deficits. The neuroinflammatory responses persist into the late repair phase of stroke and participate in all brain repair elements, including neurogenesis, angiogenesis, synaptogenesis, remyelination and axonal sprouting, shedding new light on post–stroke brain recovery. Resident brain glial cells, such as astrocytes not only contribute to neuroinflammation after stroke, but also secrete a wide range of trophic factors that can promote post–stroke brain repair. Alternatively, activated microglia, monocytes, and neutrophils in the innate immune system, traditionally considered as major damaging factors after stroke, have been suggested to be extensively involved in brain repair after stroke. The adaptive immune system may also have its bright side during the late regenerative phase, affecting the immune suppressive regulatory T cells and B cells. This review summarizes the recent findings in the evolving role of neuroinflammation in multiple post–stroke brain repair mechanisms and poses unanswered questions that may generate new directions for future research and give rise to novel therapeutic targets to improve stroke recovery.

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.

Plant root system architecture (RSA), the spatial configuration of a root system in the soil, is critical for water and nutrient acquisition. Rice generates a root system consisting of seminal, lateral, and crown/adventitious roots, whose growth and development are regulated by plant hormones and can be fine-tuned to meet adverse environmental conditions. A broad range of studies have been carried out in the past to decipher the underlying molecular and genetic mechanisms. This chapter summarizes original and more recent findings on genes and molecules identified so far to be involved in rice root development. It also discusses the cellular organization and function of rice roots, as well as the responses of RSA to the availability of water and nutrients.

Importance The burden of injury and costs of wrist fractures are substantial. Surgical treatment became popular without strong supporting evidence. Objective To assess whether current surgical treatment for displaced distal radius fractures provided better patient-reported wrist pain and function than nonsurgical treatment in patients 60 years and older. Design, Setting, and Participants In this multicenter randomized clinical trial and parallel observational study, 300 eligible patients were screened from 19 centers in Australia and New Zealand from December 1, 2016, until December 31, 2018. A total of 166 participants were randomized to surgical or nonsurgical treatment and followed up at 3 and 12 months by blinded assessors. Those 134 individuals who declined randomization were included in a parallel observational cohort with the same treatment options and follow-up. The primary analysis was intention to treat; sensitivity analyses included as-treated and per-protocol analyses. Intervention Surgical treatment was open reduction and internal fixation using a volar-locking plate (VLP). Nonsurgical treatment was closed reduction and cast immobilization (CR). Main Outcomes and Measures The primary outcome was the Patient-Rated Wrist Evaluation score at 12 months. Secondary outcomes were Disabilities of Arm, Shoulder, and Hand questionnaire score, health-related quality of life, pain, major complications, patient-reported treatment success, bother with appearance, and therapy use. Results In the 300 study participants (mean [SD] age, 71.2 [7.5] years; 269 [90%] female; 166 [81 VLP and 85 CR] in the randomized clinical trial sample and 134 [32 VLP and 102 CR] in the observational sample), no clinically important between-group difference in 12-month Patient-Rated Wrist Evaluation scores (mean [SD] score of 19.8 [21.1] for VLP and 21.5 [24.3] for CR; mean difference, 1.7 points; 95% CI −5.4 to 8.8) was observed. No clinically important differences were found in quality of life, wrist pain, or bother at 3 and 12 months. No significant difference was found in total complications between groups (12 of 84 [14%] for the CR group vs 6 of 80 [8%] for the VLP group; risk ratio [RR], 0.53; 95% CI, 0.21-1.33). Patient-reported treatment success favored the VLP group at 12 months (very successful or successful: 70 [89%] vs 57 [70%]; RR, 1.26; 95% CI, 1.07-1.48;P = .005). There was greater use of postoperative physical therapy in the VLP group (56 [72%] vs 44 [54%]; RR, 1.32; 95% CI, 1.04-1.69;P = 0.02). Conclusions and Relevance This randomized clinical trial found no between-group differences in improvement in wrist pain or function at 12 months from VLP fixation over CR for displaced distal radius fractures in older people. Trial Registration http://anzctr.org.auidentifier: ACTRN12616000969460

Zika virus was first discovered in the Zika Forest of Uganda in 1947 and was until recently believed to be an infection of mild clinical significance. Infection with Zika virus presents with mild clinical symptoms including fever, headache, rash, conjunctivitis, arthralgia, and myalgia—only a small proportion of laboratory-confirmed infections manifested clinically detectable features. In 2016 the World Health Organization declared Zika virus infection and its associated congenital malformations and neurological disorders as a Public Health Emergency of International Concern, following a large-scale outbreak of microcephaly in Brazil. Molecularly confirmed or serologically confirmed acute Zika virus infection was associated with an increased incidence of a spectrum of significant neurological manifestations including Guillain-Barre syndrome, encephalitis, and transverse myelitis. Zika virus infection during the perinatal period results in congenital Zika syndrome, a condition characterized by microcephaly, reduced head circumference, and significant craniofacial disproportion. Although Zika virus is no longer a Public Health Emergency of International Concern, Zika virus screening during pregnancy in endemic regions remains relevant and necessary, due to the severe long-term sequelae and cost to the healthcare systems involved.

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing beta cells in the pancreas. Consequently, T1D patients produce little to no insulin, resulting in absolute insulin deficiency and an inability to regulate blood glucose levels effectively. Insulin replacement is the mainstream treatment for T1D, but it comes with a major drawback—the risk of hypoglycemia unawareness. As such, replenishment of glucose-sensing and insulin-producing beta cells via cell replacement therapy is believed to have great therapeutic value for T1D patients. Human pluripotent stem cells (hPSCs) are considered an attractive source for the derivation of insulin-producing beta-like cells for cell replacement therapy. However, several challenges need to be addressed before hPSC-derived beta-like cells can be used for T1D treatment. In this chapter, we provide a snapshot of the current progress of hPSC therapy with an emphasis on T1D, discuss some of the clinical considerations and technical strategies in the generation of current good manufacturing practice (cGMP)-compliant hPSC-derived beta-like cells and the future outlook for T1D hPSC therapy.

The complex assets management system under the global optimum realizes the whole process and lean management of assets from the three aspects of organizational structure, rules and regulations. This paper analyzes the complex system of assets management from two aspects of time dimension and space dimension, in order to ensure the overall consideration and control of assets management.

[Importance] Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm., [Objective] To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes., [Data Sources] Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts., [Study Selection] Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria., [Data Extraction and Synthesis] In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality., [Main Outcomes and Measures] The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days., [Results] A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P, [Conclusions and Relevance] In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality., [Trial Registration] PROSPERO Identifier: CRD42021230155., Funding for administrative and communications support was provided by the World Health Organization.

Background Total hip and total knee replacement (THR/TKR) are common and effective surgeries to reduce the pain and disability associated with arthritis but are associated with small but significant risks of preventable complications such as surgical site infection (SSI) and venous-thrombo-embolism (VTE). This study aims to determine the degree to which hospital care was compliant with clinical guidelines for the prevention of SSI and VTE after THR/TKR; and whether non-compliant prophylaxis is associated with increased risk of complications. Methods and findings A prospective multi-centre cohort study was undertaken in consenting adults with osteoarthritis undergoing elective primary TKR/THR at one of 19 high-volume Australian public or private hospitals. Data were collected prior to surgery and for one-year post-surgery. Four adjusted logistic regression analyses were undertaken to explore associations between binary non-compliance and the risk of surgical complications: (1) composite (simultaneous) non-compliance with both (VTE and antibiotic) guidelines and composite complications [all-cause mortality, VTE, readmission/reoperation for joint-related reasons (one-year) and non-joint-related reasons (35-days)], (2) VTE non-compliance and VTE outcomes, (3) antibiotic non-compliance and any SSI, and (4) antibiotic non-compliance and deep SSI. Data were analysed for 1875 participants. Guideline non-compliance rates were high: 65% (VTE), 87% (antibiotics) and 95% (composite guideline). Composite non-compliance was not associated with composite complication (12.8% vs 8.3%, adjusted odds ratio [AOR] = 1.41, 95%CI 0.68–3.45, p = 0.40). Non-compliance with VTE guidelines was associated with VTE outcomes (5% vs 2.4%, AOR = 2.83, 95%CI 1.59–5.28,p < 0.001). Non-compliance with antibiotic guidelines was associated with any SSI (14.8% vs 6.1%, AOR = 1.98, 95%CI 1.17–3.62,p = 0.02) but not deep infection (3.7% vs 1.2%,AOR = 2.39, 95%CI 0.85–10.00, p = 0.15). Conclusions We found high rates of clinical variation and statistically significant associations between non-compliance with VTE and antibiotic guidelines and increased risk of VTE and SSI, respectively. Complications after THR/TKR surgery may be decreased by improving compliance with clinical guidelines.

Objectives Risk scoring models (RSMs) are commonly used for estimation of postoperative-mortality risk in patients undergoing cardiac surgery, but their prediction accuracy may vary in different populations and clinical situations. The prognostic accuracies of some RSMs have not yet been fully evaluated in the Australian population. In this retrospective observational study, our aims were to assess the performance of four contemporary RSMs, to identify the best RSMs for prediction of postoperative-mortality in the single-centre cohort, and to determine a statistical threshold for classification of patients with increased or “higher” mortality risk. Methods The study population included patients who underwent cardiac surgery at Liverpool Hospital between January 2013 and December 2014. Demographic information was collected, and mortality risks were estimated with the ES2 (EuroSCORE II), STS (Society of Thoracic Surgeons Score), AS (AusSCORE total) and ASMR (AusSCORE multi-risk) RSMs. (Additive EuroSCORE) (AES) and LES (logistic EuroSCORE) were included for historical interest. Discrimination, the ability to stratify patients between mortality and no mortality outcomes, and calibration, the comparison of risk score estimated and observed outcome in the population, were evaluated for each RSM, to determine their predictive accuracy in the study population. Discrimination was assessed by the AUC (area under the receiver operating characteristic curve), and acceptable calibration by the p-value greater than 0.05 for the Hosmer–Lemeshow (H-L) test. The best AUCs in contempory models were compared using the DeLong test. For ES2 and STS risk scores, cut-off points, or thresholds, for patients at increased risk of mortality were derived using Youden’s J-statistics, calculated from sensitivity and specificity of models in predicting mortality. Results From a total study population of 898 patients, 738 had scores for all six RSMs. The three EuroSCORE risk models and Youden’s J-statistics analysis included the total population. Of the models in contemporary use, ES2 had higher discrimination (AUC=0.850) in this population than ASMR (AUC=0.767, p=0.024) and AS (AUC=0.739) and non-significantly higher discrimination than STS (AUC=0.806, p=0.19). All contemporary models had acceptable calibration but the older LES (H-L p=0.024) did not. Estimated mortality was closest to observed mortality with the ES2 model. Both AES and LES over predicted mortality. The RSM with the highest discrimination in isolated coronary artery bypass graft surgery (CAGs) (AUC=0.847), isolated valves (AUC=0.830), and females (AUC=0.784) was the ES2 model. STS discrimination was highest in CAGs plus valve procedures (AUC 0.891), and males (STS AUC=0.891). Cut-off points for risk scores to define increased risk populations were 3.0% for ES2 and 1.7% for STS. Similar proportions of patients in each RSM (ES2-26% to STS-32%) were defined as higher risk by the model threshold score depending on type of procedure. Conclusion Among RSMs in contemporary use, ES2 and STS showed the best discrimination and acceptable calibration. Caution is recommended in specific subgroups. Increased mortality risk score cut-off points could be identified for these two RSMs in this single-centre cohort.

Background Models of care for managing total knee or hip arthroplasty (TKA, THA) incorporating early mobilisation are associated with shorter acute length-of-stay (LOS). Few studies have examined the effect of implementing early mobilisation in isolation, however. This study aimed to determine if an accelerated mobilisation protocol implemented in isolation is associated with a reduced LOS without undermining care. Method A Before-After (quasi-experimental) study was used. Standard practice pre-implementation of the new protocol was physiotherapist-led mobilisation once per day commencing on post-operative Day 1 (Before phase). The new protocol (After phase) aimed to mobilise patients four times by end of Day 2 including an attempt to commence on Day 0; physiotherapy weekend coverage was necessarily increased. Poisson regression modelling was used to determine associations between study period and LOS. Additional outcomes to 12 weeks post-surgery were monitored to identify unintended consequences of the new protocol. Time to first mobilisation (hours) and proportion mobilising Day 0 were monitored to assess protocol compliance. An embedded qualitative component captured staff perspectives of the new protocol. Results Five hundred twenty consecutive patients (n = 278, Before; n = 242, After) were included. The new protocol was associated with no change in unadjusted LOS, a small reduction in adjusted LOS (8.1%, p = 0.046), a reduction in time to first mobilisation (28.5 (10.8) vs 22.6 (8.1) hrs, p p Conclusion Small reductions in LOS are possible utilising an early mobilisation protocol in isolation after TKA or THA although staff burden is increased likely undermining both sustainability and the magnitude of the change. Simultaneous incorporation of other changes within the pathway would likely secure larger reductions in LOS.

Background Ultrasound (US) guidance in facilitating arterial access may reduce vascular complications and possible bleeding. There are still limited trials assessing real-time US guidance for coronary angiography. The SURF (Standard versus ultrasound-guided radial and femoral access in coronary angiography and intervention) trial showed no difference in primary outcome when the combined radial and femoral ultrasound analysis compared with standard (SD) technique, but significantly improved access efficiency and success rate. Purpose This subanalysis compared clinical and procedural outcomes of the individual radial and femoral access with US guidance versus standard technique. Methods Patients (n=1388) undergoing coronary angiography and percutaneous coronary intervention were randomised (1:1) into radial or femoral access, and (1:1) to SD or US guidance. The primary outcome was a composite of ACUITY (Acute Catheterisation and Urgent Intervention Triage strategY) major bleeding, MACE (death, stroke, myocardial infarction or urgent target lesion revascularisation) and vascular complications at 30 days. Secondary outcomes were access time, number of attempts, venepuncture, difficult accesses and first-pass success. Results Compared to standard, US guidance produced no difference in composite endpoint for both radial (1.4% vs 1.2%, p=0.78) and femoral (3.1% vs 3.8%, p=0.65) accesses. ACUITY major bleeding (radial: 0.9% US vs 0.6% SD, p=0.69; femoral: 1.9% US vs 2.3% SD, p=0.69), vascular complications (radial: 0.3% US vs 0.3% SD, p=0.98; femoral: 1.3% US vs 0.9% SD, p=0.63) and MACE (radial: 0.6% US vs 0.3% SD, p=0.59; femoral: 0.9% US vs 1.2% SD, p=0.78) were similar in the US and SD approaches, respectively. However, US guidance resulted in improved procedural outcomes for both accesses. Femoral access derived the most benefit from US, with reduced mean access time (73 sec vs 97 sec, p=0.006), attempts (1.35 vs 1.84, p≤0.0001), difficult accesses (1.8% vs 6.2%, p=0.004), venepuncture (5.8% vs 12.6%, p=0.002) and improved first-pass success (77.2% vs 58.8%, p≤0.0001). For radial, US reduced attempts (1.59 vs 1.97, p=0.0007), difficult accesses (6.9% vs 12.3%, p=0.02), venepuncture (2.5% vs 5.6%, p=0.04) and improved first-pass success (69.2% vs 60.7%, p=0.02). There was no difference in radial mean access time (111 sec vs 126 sec, p=0.18). Conclusions US guidance in radial and femoral access did not reduce primary outcome compared to standard technique. The use of US significantly improved the efficiency and success rate of arterial cannulation, with femoral access derived the most benefit. Funding Acknowledgement Type of funding source: None

BACKGROUND Colonoscopy remains the gold standard for detection of colonic disease. An optimal evaluation depends on adequate bowel cleansing. Patients with inflammatory bowel disease (IBD), require frequent endoscopic assessment for both activity and dysplasia assessment. Two commonly used bowel preparations in Australia are Prep Kit-C (Pc) and Moviprep (Mp). Little is known about tolerability, efficacy and safety of split protocols of Mp and Pc in both IBD and non-IBD patients. AIM To primary aim was to compare the tolerability, efficacy and safety of split protocols of Mp and Pc in patients having a colonoscopy. The secondary aim was to compare the efficacy, tolerability and safety of either preparation in patients with or without IBD. METHODS Patients were randomized to Pc or Mp bowel preparation. Patients completed a questionnaire to assess tolerability. Efficacy was assessed using the Ottawa Bowel Preparation Score. Serum electrolytes and renal function were collected one week prior to colonoscopy and on the day of colonoscopy. RESULTS Of 338 patients met the inclusion criteria. Of 168 patients randomized to Mp and 170 to Pc. The efficacy of bowel preparation (mean Ottawa Bowel Preparation Score) was similar between Mp (5.4 ± 2.4) and Pc (5.1 ± 2.1) (P = 0.3). Mean tolerability scores were similar in Mp (11.84 ± 5.4) and Pc (10.99 ± 5.2; P = 0.17). 125 patients had IBD (73 had Crohn's Disease and 52 had Ulcerative colitis). Sixty-four IBD patients were allocated to Mp and 61 to Pc. In non-IBD patients, 104 were allocated to Mp and 109 to Pc. The mean tolerability score in the IBD group was lower than the non-IBD group (mean tolerability scores: IBD: 10.3 ± 5.1 and non-IBD: 12.0 ± 5.3; P = 0.01). IBD patients described more abdominal pain with Mp when compared with Pc; (Mp: 5.7 ± 4.4 vs Pc: 3.6 ± 2.6, P = 0.046). Serum magnesium level increased with Pc compared with Mp in all patients (mean increase in mmol/L: Mp: 0.03 ± 0.117 and Pc: 0.11 ± 0.106; P < 0.0001). CONCLUSION In this study, the efficacy, tolerability and safety of Mp and Pc were similar in all patients. However, patients with IBD reported lower tolerability with both preparations. Specifically, IBD patients had more abdominal pain with Mp. These results should be considered when recommending bowel preparation especially to IBD patients.

Objective Transdifferentiation exists between stromal cells or between stromal cells and cancer cells. Evodiamine and berberine are predominant pharmacological components of Zuojin pill, a prescription of Traditional Chinese Medicine, playing crucial functions in remolding of tumor microenvironment. This study aimed to explore the effect of combination of evodiamine with berberine (cBerEvo) on the phenotypic transition of colon epithelial cells induced by tumor-associated fibroblasts, as well as the involved mechanisms.Methods Human normal colon epithelial cell line HCoEpiC cells were treated with the prepared conditioned medium of CCD-18Co, a human colon myofibroblast line, to induce epithelial-mesenchymal transition. Phase contrast microscope was used to observe the morphological changes. Epithelial-mesenchymal transition markers including E-cadherin, vimentin and alpha-smooth muscle actin (α-SMA) were observed with immunofluorescence microscopy. Migration was assessed by wound healing assay. Western blotting was used to detect the expressions of E-cadherin, vimentin, α-SMA, Snail, ZEB1 and Smads. Results In contrast to the control, the tumor-associated fibroblasts-like CCD-18Co cells induced down-regulation of E-cadherin and up-regulation of vimentin, α-SMA, Snail and ZEB1 (P