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Background: We tested the hypothesis that overexpression of cellular-prion-protein in adipose-derived mesenchymal stem cells (PrPC OE -ADMSCs) effectively protected the kidney against ischemia-reperfusion (IR) injury in rat. Methods: Part I of cell culture was categorized into A1(ADMSCs)/A2(ADMSCs+p-Cresol)/A3(PrPC OE in ADMSCs)/A4 (PrPC OE in ADMSCs+p-Cresol). Part II of cell culture was divided into B1(ADMSCs)/B2[ADMSCs+lipopolysaccharide (LPS)]/B3(PrPC OE in ADMSCs)/B4(PrPC OE in ADMSCs+LPS). Sprague-Dawley (SD) rats (n = 50) were equally categorized into groups 1 (sham-operated-control)/2 (IR)/3 (IR+ADMSCs/6.0 × 10 5 equally divided into bilateral-renal arteries and 6.0 × 10 5 intravenous administration by 1 h after IR)/4 [IR+PrPC OE -ADMSCs (identical dosage administered as group 3)]/5 [IR+silencing PRNP -ADMSCs (identical dosage administered as group 3)], and kidneys were harvested post-day 3 IR injury. Results: Part I results demonstrated that the cell viability at 24/48/72 h, BrdU uptake/number of mitDNA/APT concentration/mitochondrial-cytochrome-C+ cells and the protein expressions of ki67/PrPC at 72 h-cell culturing were significantly higher in PrPC OE -ADMSCs than in ADMSCs (all P < 0.001). The protein expressions of oxidative-stress (NOX-1/NOX2/NOX4/oxidized protein)/mitochondrial-damaged (p22-phox/cytosolic-cytochrome-C)/inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers were lowest in A1/A3 and significantly higher in A2 than in A4 (all P < 0.001). Part II result showed that the protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers exhibited an identical pattern of part I among the groups (all P < 0.001). The protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized-protein)/mitochondrial-damaged (cytosolic-cytochrome-C/p22-phox)/apoptotic (cleaved caspase-3/cleaved-PARP/mitochondrial-Bx)/autophagic (beclin-1/ratio of LC3B-II/LC3B-I)/fibrotic (Smad3/TGF-ß) biomarkers and kidney-injury-score/creatinine level were lowest in group 1, highest in group 2, significantly higher in group 5 than in groups 3/4 (all P < 0.0001). Conclusion: PrPC OE in ADMSCs rejuvenated these cells and played a cardinal role on protecting the kidney against IR injury.

This study tested whether human umbilical cord–derived mesenchymal stem cells (HUCDMSCs) treatment effectively protected the rat lung against acute respiratory distress syndrome (ARDS) injury, and benefits of early and dose-dependent treatment. Rat pulmonary epithelial cell line L2 (PECL2) were categorized into G1 (PECL2), G2 (PECL2 + healthy rat lung-derived extraction/50 mg/ml co-cultured for 24 h), G3 (PECL2 + ARDS rat lung-derived extraction/50 mg/ml co-cultured for 24 h), and G4 (condition as G3 + HUCDMSCs/1 × 10 5 /co-cultured for 24 h). The result showed that the protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IkB/NF-κB/IL-1β/TNF-α), oxidative-stress/mitochondrial-damaged (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/JNKs/JUN/cytosolic-cytochrome-C/cyclophilin-D/DRP1), and cell-apoptotic/fibrotic (cleaved-caspase 3/cleaved-PARP/TGF-β/p-Smad3) biomarkers were significantly increased in G3 than in G1/G2 and were significantly reversed in G4 (all P < 0.001), but they were similar between G1/G2. Adult male rats ( n = 42) were equally categorized into group 1 (normal control), group 2 (ARDS only), group 3 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 3 h after 48 h ARDS induction (i.e., early treatment)], group 4 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 24 h after 48 h ARDS induction (late treatment)], and group 5 [ARDS + HUCDMSCs/1.2 × 10 6 cells intravenous administration at 3 h/24 h after-48 h ARDS induction (dose-dependent treatment)]. By day 5 after ARDS induction, the SaO 2 %/immune regulatory T cells were highest in group 1, lowest in group 2, significantly lower in group 4 than in groups 3/5, and significantly lower in group 3 than in group 5, whereas the circulatory/bronchioalveolar lavage fluid inflammatory cells (CD11b-c+/LyG6+/MPO+)/circulatory immune cells (CD3-C4+/CD3-CD8+)/lung-leakage-albumin level/lung injury score/lung protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IκB-β/p-NF-κB/IL-1β/TNF-α)/fibrotic (p-SMad3/TGF-β), apoptosis (mitochondrial-Bax/cleaved-caspase-3)/oxidative-cell-stress (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/p-JNKs/p-cJUN)/mitochondrial damaged (cyclophilin-D/DRP1/cytosolic-cytochrome-C) biomarkers displayed an opposite pattern of SaO 2 % among the groups (all P < 0.0001). Early administration was superior to and two-dose counterpart was even more superior to late HUCDMSCs treatment for protecting the lung against ARDS injury.

Abstract The use of extended antibiotic (EA) prophylaxis (> 24 h) remains controversial in aseptic revision arthroplasty. We sought to determine whether EA prophylaxis reduces the risk of periprosthetic joint infection (PJI) in aseptic revision hip and knee arthroplasty. A total of 2800 patients undergoing aseptic revision hip and knee arthroplasty at five institutional databases from 2008 to 2017 were evaluated. One to two nearest-neighbor propensity score matching analysis was conducted between patients who did and did not receive extended antibiotic prophylaxis. The matching elements included age, sex, body mass index, Charlson comorbidity index, hospital distribution, year of surgery, joint (hip or knee), surgical time, CRP, preoperative hemoglobin, albumin, and length of stay. The primary outcome was the development of PJI, which was assessed at 30 days, 90 days, and 1 year following revision and analyzed separately. A total of 2467 (88%) patients received EA prophylaxis, and 333 (12%) patients received standard antibiotic (SA) prophylaxis (≤ 24 h). In the propensity-matched analysis, there was no difference between patients who received EA prophylaxis and those who did not in terms of 30-day PJI (0.3% vs. 0.3%, p = 1.00), 90-day PJI (1.7% vs. 2.1%, p = 0.62) and 1- year PJI (3.8% vs. 6.0%, p = 0.109). For revision hip, the incidence of PJI was 0.2% vs 0% at 30 days (p = 0.482), 1.6% vs 1.4% at 90 days (p = 0.837), and 3.4% vs 5.1% at 1 year (p = 0.305) in the EA and SA group. For revision knee, the incidence of PJI was 0.4% vs 0.9% at 30 days (p = 0.63), 1.8% vs 3.4% at 90 days (p = 0.331), and 4.4% vs 7.8% at 1 year (p = 0.203) in the EA and SA group. A post hoc power analysis revealed an adequate sample size with a beta value of 83%. In addition, the risks of Clostridium difficile and resistant organism infection were not increased. This multi-institutional study demonstrated no difference in the rate of PJIs between patients who received extended antibiotic prophylaxis and those who did not in aseptic revision arthroplasty. The risk of C. difficile and resistant organism infection was not increased with prolonged antibiotic use.

This study tested whether combined hyperbaric oxygen (HBO) and allogenic adipose-derived mesenchymal stem cells (ADMSCs) would be superior to either one for improving the locomotor recovery in rat after acute traumatic spinal cord injury (TSCI) in rat. Adult-male Sprague–Dawley rats were equally categorized into group 1 (sham-operated control), group 2 (TSCI), group 3 (TSCI + HBO for 1.5 h/day for 14 consecutive days after TSCI), group 4 (TSCI + ADMSCs/1.2 × 10 6 cells by intravenous injection at 3 h and days 1/2 after TSCI), and group 5 (TSCI + HBO + ADMSCs), euthanized, and spinal cord tissue was harvested by day 49 after TSCI. The protein expressions of oxidative-stress (NOX-1/NOX-2), inflammatory-signaling (TLR-4/MyD88/IL-1β/TNF-α/substance-p), cell-stress signaling (PI3K/p-AKT/p-mTOR), and the voltage-gated sodium channel (Nav1.3/1.8/1.9) biomarkers were highest in group 2, lowest in group 1, and significantly lower in group 5 than in groups 3/4 (all P

(1) Background: Hip degenerative disorder is a common geriatric disease is the main causes to lead to total hip replacement (THR). The surgical timing of THR is crucial for post-operative recovery. Deep learning (DL) algorithms can be used to detect anomalies in medical images and predict the need for THR. The real world data (RWD) were used to validate the artificial intelligence and DL algorithm in medicine but there was no previous study to prove its function in THR prediction. (2) Methods: We designed a sequential two-stage hip replacement prediction deep learning algorithm to identify the possibility of THR in three months of hip joints by plain pelvic radiography (PXR). We also collected RWD to validate the performance of this algorithm. (3) Results: The RWD totally included 3766 PXRs from 2018 to 2019. The overall accuracy of the algorithm was 0.9633; sensitivity was 0.9450; specificity was 1.000 and the precision was 1.000. The negative predictive value was 0.9009, the false negative rate was 0.0550, and the F1 score was 0.9717. The area under curve was 0.972 with 95% confidence interval from 0.953 to 0.987. (4) Conclusions: In summary, this DL algorithm can provide an accurate and reliable method for detecting hip degeneration and predicting the need for further THR. RWD offered an alternative support of the algorithm and validated its function to save time and cost.

Abstract Background This study aimed to evaluate the effect of dipyridamole-thallium scanning (DTS) on the rates of 90-day cardiac complications and 1-year mortality in patients with a femoral neck fracture treated with hemiarthroplasty. Methods Between 2008 and 2015, 844 consecutive patients who underwent cemented or cementless hemiarthroplasty were identified from the database of a single level-one medical center. One-hundred and thirteen patients (13%) underwent DTS prior to surgery, and 731 patients (87%) did not. Patient characteristics, comorbidities, surgical variables, and length of the delay until surgery were recorded. A propensity score-matched cohort was utilized to reduce recruitment bias in a 1:3 ratio of DTS group to control group, and multivariate logistic regression was performed to control confounding variables. Results The incidence of 90-day cardiac complications was 19.5% in the DTS group and 15.6% in the control group (p = 0.343) among 452 patients after propensity score-matching. The 1-year mortality rate (10.6% vs 13.3%, p = 0.462) was similar in the two groups. In the propensity score-matched patients, utilization of DTS was not associated with a reduction in the rate of 90-day cardiac complications (matched cohort, adjusted odds ratio [aOR] = 1.32; 95% confidence interval [CI] 0.75–2.33, p = 0.332) or the 1-year mortality rate (aOR = 0.62; 95% CI 0.27–1.42, p = 0.259). Risk factors for cardiac complications included an American Society of Anesthesiologists grade ≥ 3 (OR 3.19, 95% CI 1.44–7.08, p = 0.004) and pre-existing cardiac comorbidities (OR 5.56, 95% CI 3.35–9.25, p < 0.001). Risk factors for 1-year mortality were a long time to surgery (aOR 1.15, 95% CI 1.06–1.25, p = 0.001), a greater age (aOR 1.05, 95% CI 1.00 to 1.10, p = 0.040), a low body mass index (BMI; aOR 0.89, 95% CI 0.81–0.98, p = 0.015), and the presence of renal disease (aOR 4.43, 95% CI 1.71–11.46, p = 0.002). Discussion Preoperative DTS was not associated with reductions in the rates of 90-day cardiac complications or 1-year mortality in patients with a femoral neck fracture undergoing hemiarthroplasty. The necessity for DTS should be re-evaluated in elderly patients with femoral neck fractures, given that this increases the length of the delay until surgery. Level of evidence Prognostic level III

Abstract Background This was a randomized, open‐label, controlled phase II clinical trial to investigate the safety, efficacy, and outcomes of intrarenal artery infusion of autologous peripheral‐blood‐derived CD34+ cells for patients with chronic kidney disease (CKD; ie, stage III or IV). Materials and Methods Between October 2016 and July 2018, 52 consecutive patients with CKD at stage III or IV were randomly allocated into a treatment group (TG; 2.5 × 107 cells for each intrarenal artery; n = 26) and a control group (CG; standardized pharmacotherapy only; n = 26). The primary endpoints included safety and change of creatinine level/creatinine clearance. The secondary endpoints were 12‐month combined unfavorable clinical outcomes (defined as dialysis or death), improvement in proteinuria, and CD34+ cell‐related adverse events. Results All patients were uneventfully discharged after CD34+ cell therapy. The baseline endothelial progenitor cell (EPC) populations did not differ between TG and CG (P > .5). Flow cytometric analysis showed increases in circulating EPC (ie, CD34+KDR+CD45dim/ CD34+CD133+CD45dim/CD31+CD133+CD45dim/CD34+CD133+KDR+/CD133+) and hematopoietic stem cell (CD34+) populations after granulocyte‐colony stimulating factor treatment (all P .1). Conclusion CD34+ cell therapy was safe and improved 1‐year outcome.

Abstract Background Treating patients with end-stage diffuse coronary artery disease (EnD-CAD) unsuitable for coronary intervention remains a clinical challenge. They usually express refractory angina and have a high risk of mortality. Although growing data have indicated cell therapy is an alternative solution to medical or invasive therapy, there are still lacking useful markers to predict whether heart function will improve in the EnD-CAD patients who underwent circulatory-derived CD34+ cell therapy. By utilizing the baseline variables and results from our previous phase I/II clinical trials, the aim of this study tried to elucidate the variables predictive of the “good response” to CD34+ cell therapy. Methods This retrospective study included 38 patients in phase I clinical trial (2011–2014), and 30 patients in phase II clinical trial (2013–2017). These patients were categorized into “good responders” and “non-responders” according to their 1-year improvement of LVEF ≥ 7.0% or

Unacceptable sagittal alignment and cement leakage are major concerns of percutaneous vertebroplasty when treating patients with painful vertebral osteoporotic compression fractures. To maintain the restored vertebral height and reduce the reliance on cement as the major stabilizer, an expandable vertebral augment system (EVA®) made of titanium alloy consisting of a rigid tube encased by a barrel with an anterior expansion mechanism was developed. The aim of the current study was to determine whether this novel design is as effective as existing procedures in terms of height restoration and biomechanical performance. Eight osteoporotic vertebrae (T12-L3) confirmed by dual-energy X-ray absorptiometry from two fresh-frozen human cadavers (70- and 72-year-old females) were used. Twenty-five percent reduced anterior wedge vertebral compression fractures were created using a material testing machine. Four randomized specimens were augmented with EVA® (Chang Gu Biotechnology Co. Ltd., Taipei city, Taiwan), and another four randomized specimens were augmented with OsseoFix® (AlphaTec Spine Inc., Carlsbad, CA, USA). The implant size and cement volume were controlled. The anterior vertebral body height (VBH) ratio and pre/postaugmented ultimate strength and stiffness were measured and compared. The mean anterior VBH restoration ratio was 8.54% in the EVA® group and 8.26% in the OsseoFix® groups. A significant difference from augmentation was measured in both groups (p < 0.05), but there was no significant difference between the EVA® and OsseoFix® groups in anterior VBH restoration. The ultimate strengths of the EVA® and OsseoFix® groups were 6071.4 ± 352.6 N and 6262.9 ± 529.2 N, respectively, both of which were statistically significantly higher than that of the intact group (4589.9 ± 474.6 N) (p < 0.05). The stiffnesses of the EVA®, OsseoFix®, and intact groups were 1087.2 ± 176.9, 1154.9 ± 168.9, and 1637.3 ± 340.8 N/mm, respectively, indicating that the stiffness was significantly higher in the intact group than in both the EVA® and OsseoFix® groups (p < 0.05). No significant differences were observed between the two augmentation procedures in height restoration or ultimate strength and stiffness. This novel EVA® system showed comparable height restoration and biomechanical performance to those of existing implants for human cadaveric osteoporotic compression fractures. Potential advantages of preventing cement posterior leakage and promoting cement interdigitation are expected with this ameliorated design.

Background:. Patients undergoing total joint arthroplasty (TJA) following septic arthritis are at higher risk for developing periprosthetic joint infection (PJI). Minimal literature is available to guide surgeons on the optimal timing of TJA after completing treatment for prior native joint septic arthritis. This multicenter study aimed to determine the optimal timing of TJA after prior septic arthritis and to examine the role of preoperative serology in predicting patients at risk for developing PJI. Methods:. A total of 207 TJAs were performed after prior septic arthritis from 2000 to 2017 at 5 institutions. Laboratory values, prior treatment, time from the initial infection, and other variables were recorded. Bivariate analyses were performed to identify the association between the time from septic arthritis to TJA and the risk of developing subsequent PJI. A subanalysis was performed between patients who underwent TJA in 1 setting (n = 97) compared with those who underwent 2-stage arthroplasties (n = 110). Receiver operating characteristic (ROC) curve analysis was performed for serum markers prior to TJA in predicting the risk of a subsequent PJI. Results:. The overall PJI rate was 12.1%. Increasing time from septic arthritis treatment to TJA was not associated with a reduction of PJI, whether considering time as a continuous or categorical variable, for both surgical treatment cohorts (all p > 0.05). Although the ROC curve analysis found that the optimal threshold for timing of TJA from the initial treatment was 5.9 months, there was no difference in the PJI rate when the overall cohort was dichotomized by this threshold and when stratified by 1-stage compared with 2-stage TJA. There was no significant difference in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level prior to conversion TJA between patients who subsequently developed PJI and those who did not. Conclusions:. Serum markers have limited value in predicting subsequent PJI in patients who undergo TJA after prior septic arthritis. There was no optimal interim period between septic arthritis treatment and subsequent TJA; thus, delaying a surgical procedure does not appear to reduce the risk of PJI. Level of Evidence:. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background: Endothelial cell dysfunction plays the crucial role in initiation and propagation of obstructive arteriosclerosis which ultimately causes arterial obstructive syndrome. Additionally, severe endothelial progenitor cells (EPC) dysfunction is always found in those of end-stage renal disease (ESRD) patients. This study tested the hypothesis that a novel method, named “quality and quantity (QQ) culture”, could successfully improve the EPC proliferation and function in ESRD patients. Materials and methods: Peripheral blood mononuclear cells (PBMNCs) were isolated from age-matched control subjects (i.e., normal renal function) (group 1) and ESRD patients (group 2), followed by culture in either conventional EPC culture for one month or in QQ culture for 7 days, respectively. The result showed that as compared to the conventional EPC culture method, the EPC population and M2-like population/ratio (M2/M1) were significantly enriched in QQ culture both in groups 1 and 2 (all p

Abstract Background This study aimed to investigate the risk factors for mechanical failure of cement spacers and the impact on hip function after two-stage exchange arthroplasty for periprosthetic joint infection (PJI). Methods Thirty-one patients (19 males and 12 females) with hip PJIs underwent resection arthroplasty and implantation of cement spacers from January 2014 to December 2015. Patients who encountered spacer-associated mechanical complications in the interim period (14 of 31) were compared with those without complications (17 of 31). Complications were defined as spacer dislocation, spacer fracture, spacer fracture with dislocation, and femoral fracture during or following spacer implantation. Hip functional outcome was assessed using the Harris hip score (HHS). Treatment success was defined according to the following criteria: (1) no symptoms or signs indicative of infection; (2) no PJI-related mortality; and (3) no subsequent surgical intervention for infection after reimplantation surgery. Multivariate logistic regression and Kaplan-Meier survival curves were used for analysis. Results Fourteen patients (14/31 = 45%) suffered at least one spacer-related complication within the interim period. The development of spacer complications was associated with a younger age (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.83–1.00, p = 0.045) and chronic PJI (OR 14.7, 95% CI 1.19–182, p = 0.036). Patients with spacer complications also had a lower median HHS (37 vs. 60, p

Abstract Background Femoroacetabular impingement (FAI) is associated with decreased hip function and early hip osteoarthritis. Surgical treatment is often required to halt the process of mechanical degeneration. The study investigated the short-to-midterm results of using a modified anterolateral mini-open and arthroscopic osteochondroplasty in the treatment of cam-type FAI. Methods Thirty-six patients (39 hips), with the mean age of 43.6 years, who had cam-type FAI, were operated by a mini-open and arthroscopy-assisted osteochondroplasty via the Watson-Jones interval between 2002 and 2016. Radiographic parameters and Harris hip scores were retrospectively analyzed after a mean follow-up of 44 months. Results Of the 39 hips, the mean Harris hip score significantly improved from 61.1 preoperatively to 84.2 postoperatively (P

This study tested whether sitagliptin and shock wave (SW)-assisted circulatory-derived autologous endothelial progenitor cell (EPC) therapy would effectively preserve residual renal function in chronic kidney disease (CKD) induced by 5/6 left-nephrectomy/remove right kidney plus daily feeding high-protein diet (HPD) in rat. Adult-male SD rats (n = 40) were categorized into group 1 (sham-operated control with HPD), group 2 (HPD-CKD), group 3 [HPD-CKD + EPC (1.2 × 106 cell)/intra-vessel administration by day 14 after CKD-induction], group 4 [HPD-CKD + SW (0.12 mJ/mm2/180 shorts) at days 14/21/28 after CKD-induction by ultrasound-guided application] and group 5 [HPD-CKD + SW + EPC + sitagliptin (Sita; 600 mg/kg/day since day 14 after CKD induction)]. All animals were euthanized by day 60. By day 60, renal blood flow (RBF) was highest in group 1 and progressively increased from groups 2 to 5, whereas the levels of creatinine/BUN/proteinuria exhibited an opposite pattern of RBF among the five groups (all p

The administration of zoledronic acid (ZA) to patients who received cementless total hip arthroplasty (THA) has been reported to reduce bone turnover markers (BTMs) and increase bone mineral density (BMD). The effects of two-dose ZA versus placebo on cementless THA patients were analyzed in this five-year extension study. Alkaline phosphatase (ALP), osteocalcin (OC), procollagen 1 intact N-terminal propeptide (P1NP), serum calcium, renal function, radiological findings, and functional outcomes were compared in 49 patients, and the periprosthetic BMD of seven Gruen zones were compared in 19 patients. All the patients had normal renal function and calcium levels at their final follow-up. The mean ALP level in the ZA group was significantly lower at the fifth year, mean OC levels were significantly lower at the second and fifth year, and mean P1NP levels were significantly lower from 6 weeks to 5 years as compared with the control group. Fifth-year BMD levels were not found to be different between the ZA and control groups. The BMD Change Ratios in the ZA group were significantly increased in Gruen zone 6 at 1, 2, and 5 years. Our study results suggest that short-term ZA treatment with a subsequent 4-year drug holiday may inhibit serum BTMs and provide periprosthetic bone preservation at five years without adverse events.

Intracranial hemorrhage from stroke and head trauma elicits a cascade of inflammatory and immune reactions detrimental to neurological integrity and function at cellular and molecular levels. This study tested the hypothesis that human umbilical cord–derived mesenchymal stem cell (HUCDMSC) therapy effectively protected the brain integrity and neurological function in rat after acute traumatic brain injury (TBI). Adult male Sprague-Dawley rats ( n = 30) were equally divided into group 1 (sham-operated control), group 2 (TBI), and group 3 [TBI + HUCDMSC (1.2 × 10 6 cells/intravenous injection at 3 h after TBI)] and euthanized by day 28 after TBI procedure. The results of corner test and inclined plane test showed the neurological function was significantly progressively improved from days 3, 7, 14, and 28 in groups 1 and 3 than in group 2, and group 1 than in group 3 (all P < 0.001). By day 28, brain magnetic resonance imaging brain ischemic volume was significantly increased in group 2 than in group 3 ( P < 0.001). The protein expressions of apoptosis [mitochondrial-bax positive cells (Bax)/cleaved-caspase3/cleaved-poly(adenosine diphosphate (ADP)-ribose) polymerase], fibrosis (Smad3 positive cells (Smad3)/transforming growth factor-β), oxidative stress (NADPH Oxidase 1 (NOX-1)/NADPH Oxidase 2 (NOX-2)/oxidized-protein/cytochrome b-245 alpha chain (p22phox)), and brain-edema/deoxyribonucleic acid (DNA)–damaged biomarkers (Aquaporin-4/gamma H2A histone family member X ( (γ-H2AX)) displayed an identical pattern to neurological function among the three groups (all P < 0.0001), whereas the protein expressions of angiogenesis biomarkers (vascular endothelial growth factor/stromal cell–derived factor-1α/C-X-C chemokine receptor type 4 (CXCR4)) significantly increased from groups 1 to 3 (all P < 0.0001). The cellular expressions of inflammatory biomarkers (cluster of differentiation 14 (+) cells (CD14+)/glial fibrillary acidic protein positive cells (GFAP+)/ a member of a new family of EGF-TM7 molecules positive cells (F4/80+)) and DNA-damaged parameter (γ-H2AX) exhibited an identical pattern, whereas cellular expressions of neural integrity (hexaribonucleotide Binding Protein-3 positive cells (NeuN+)/nestin+/doublecortin+) exhibited an opposite pattern of neurological function among the three groups (all P < 0.0001). Xenogeneic HUCDMSC therapy was safe and it significantly preserved neurological function and brain architecture in rat after TBI.

Abstract Background Acute ischemic stroke is a leading cause of mortality and long-term disability, and profiles of endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment. This study tested the hypothesis that hyperbaric oxygen therapy (HBOT) both improves the clinical short-term outcomes and increases the number of circulating EPCs and antioxidant capacity. Methods The numbers of circulating EPCs [CD133+/CD34+ (%), KDR+/CD34+ (%)], biomarkers for oxidative stress (thiols and thiobarbituric acid-reactive substances), and clinical scores (National Institutes of Health Stroke Scale [NIHSS], Barthel index [BI], and modified Rankin Scale [MRS]) were prospectively evaluated in 25 patients with acute non-cardioembolic stroke under HBOT at two time points (pre- and post-HBOT). The biomarkers and clinical scores were compared with those of 25 age- and sex-matched disease controls. Results The numbers of KDR+/CD34+ (%) in the HBOT group following HBOT increased significantly, whereas the numbers of CD133+/CD34+ (%) also showed a tendency to increase without statistical significance. The mean high-sensitivity C-reactive protein levels showed significant decrease post-HBOT follow-up in the HBOT group. The changes in KDR+/CD34+EPC (%) numbers were positively correlated with changes in clinical outcomes scores (BI, NIHSS, and MRS) in the HBOT group. Conclusions Based on the results of our study, HBOT can both improve short-term clinical outcomes and increase the number of circulating EPCs in patients with acute non-cardioembolic stroke.

Background Hepatitis C virus (HCV) infection not only links closely to systemic inflammation but also has numerous extrahepatic manifestations. Chronic inflammation also increases the risk of new‐onset atrial fibrillation (AF). However, little is known regarding the clinical association between HCV infection and new‐onset AF. Methods and Results We conducted a population‐based cohort study using Taiwan's National Health Insurance Research Database during 1997 to 2013. A total of 11 771 HCV‐infected patients were included in this study, and each of them was matched in a ratio of 1:4. Because of higher mortality among HCV cohorts, we used both Cox proportional hazard regression and competing risk regression models to compute the hazard ratios accompanying 95% CIs after adjustment for relevant confounder. The results demonstrated that the patients with chronic HCV infection had significantly higher incidence rate (332.0 versus 265.8 in 100 000 person‐years, P

In this paper, a deep belief network (DBN) is proposed as an effective method to predict the mortality of patients within the first 72 h of visiting an emergency room (ER), i.e., 72-h mortality. Previously, physicians used the quick sequential organ failure assessment (qSOFA) and systemic inflammatory response syndrome (SIRS) to determine the survival probability of patients. Although such prediction methods are convenient, there is room for improvement in their accuracy. To demonstrate the effectiveness of our proposed method, original data from a hospital was used. A single-center retrospective study was performed regarding adult ER patients who were admitted between January 2007 and December 2013 with an infection. The qSOFA and SIRS scores were calculated using primary vital signs and laboratory data. A DBN was then used to predict patients’ survival rates and to choose 65 clinical variables as an input. Utilizing the DBN, the joint probability distribution of the 65 clinical variables was calculated, and valid solutions of the decreased features were achieved. Results indicate that the DBN can predict the 72-h mortality of ER septic patients more accurately than the qSOFA or SIRS. This paper aims to design an effective prediction system to assist clinicians in their diagnosis using a DBN for early risk stratification and intervention.

Abstract Background Resistant staphylococcal organisms remain a serious problem in the treatment of periprosthetic joint infection (PJI). Higher failure rates have been reported when vancomycin was used. The purpose of this study was to assess the clinical dosage, effect, and safety of daptomycin in patients with resistant staphylococcal PJI. Methods We retrospectively enrolled patients with hip or knee PJI who were treated with daptomycin in our institution (n = 16) from January 2013 to December 2014 with a minimum follow-up of 2 years. The patients received daptomycin when glycopeptide could not be used due to multiple resistance, any adverse reaction, chronic kidney disease stage 3 or worse, and previous treatment failure with glycopeptide or empirical therapy. Results These patients received daptomycin at a median dose of 8.3 mg∕kg per day for a median duration of 14 days. The overall treatment success rate was 87.5% (14 of 16 cases) after a median follow-up period of 27 months. In the subgroups of acute and chronic PJI, the success rate was 80% and 91%, respectively. One patient developed asymptomatic transient serum aspartate transaminase (AST) elevation. No severe side effects such as myositis, acute renal failure due to rhabdomyolysis or eosinophilic pneumonia were found in our series. Conclusion Relatively high daptomycin doses combined with adequate surgical intervention were effective in treating resistant staphylococcal PJI. Daptomycin is an option worthy of consideration in PJI patients for whom glycopeptide treatment is unsuitable. Further prospective randomized comparative study is needed in the future.

This study tested whether extracorporeal shock wave (ECSW) supported-exogenous mitochondria (Mito) into adipose-derived mesenchymal stem cells (ADMSCs) would preserve left-ventricular-ejection-fraction (LVEF) in doxorubicin/12 mg/kg-induced dilated cardiomyopathy (DCM) rat. Adult-male-SD rats were equally categorized into group 1 (sham-control), group 2 (DCM), group 3 (DCM + ECSW/1.5 mJ/mm2 for 140 shots/week × 3 times/since day 14 after DCM induction), group 4 (DCM + ECSW/1.5 mJ/mm2/100 shots-assisted mito delivery (500 μg) into ADMSCs/1.2 × 106 cells, then implanted into LV myocardium day 14 after DCM induction) and group 5 (DCM + ECSW-assisted mito delivery into ADMSCs/1.2 × 106 cells, then implanted into LV, followed by ECSW/1.5 mJ/mm2 for 140 shots/week × 3 times/since day 14 after DCM induction) and euthanized by day 49. Microscopic findings showed mitochondria were abundantly enhanced by ECSW into H9C2 cells. The q-PCR showed a significant increase in relative number of mitDNA in mitochondrial-transferred H9C2 cells than in control group (p < 0.01). The angiogenesis/angiogenesis factors (VEGF/SDF-1α/IG-F1) in HUVECs were significantly progressively increased by a stepwise-increased amount of ECSW energy (0.1/0.25/0.35 mJ/mm2) (all p < 0.001). The 49-day LVEF was highest in group 1 and significantly progressively increased from groups 2 to 5 (all p < 0.0001). Cardiomyocyte size/fibrosis exhibited an opposite pattern of LVEF, whereas cellular/protein levels of angiogenesis factors (VEGF/SDF-1α) in myocardium were significantly progressively increased from groups 1 to 5 (all p < 0.0001). The protein expressions of apoptotic/mitochondrial (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax/cytosolic-cytochrome-C), fibrotic (p-Smad3/TGF-ß), oxidative-stress (NOX-1/NOX-2) and pressure-overload/heart failure (BNP/ß-MHC) biomarkers exhibited an opposite pattern of LVEF among the five groups (all p < 0.0001). ECSW-assisted mitochondrial-delivery into ADMSCs plus ECSW offered an additional benefit for preserving LVEF in DCM rat.

Abstract Synovitis contributes to the development of osteoarthritis (OA) of the knee. MicroRNAs regulate joint microenvironment homeostasis and deterioration. This study was undertaken to characterize the actions of microRNA-29a (miR-29a) to synovial remodeling in OA joints. Synovial specimens isolated from patients with end-stage OA knees showed abundant fibrotic matrix and vessel histopathology concomitant with weak miR-29a expression. In vitro, miR-29a knockdown caused synovial fibroblasts to exhibit high expressions of collagen III, TGF-β1, MMP9, MMP13, and ADAMTS5, whereas miR-29a overexpression diminished these joint-deleterious factors. In collagenase-mediated OA pathogenesis, miR-29a-overexpressing transgenic mice showed minor responses to hyperplasia, macrophage infiltration, fibrosis, hyperangiogenesis, and VEGF expression in synovial lesions. These effects mitigated articular cartilage loss and gait aberrance of injured joints. Intra-articular administration of miR-29a precursor lessened the collagenase aggravation of excessive synovial remodeling reactions and thereby sustained joint tissue integrity. miR-29a lowered VEGF production and angiogenic activities in synovial fibroblasts through targeting the 3′-UTR of VEGF. Taken together, miR-29a deficiency exacerbated synovitis pathogenesis in the end-stage OA knees. miR-29a signaling fends off excessive synovial angiogenesis and fibrosis, which delays joint destruction. This study sheds new light on the protective effects against synovial deterioration and the therapeutic advantage of miR-29a in OA knees.

Abstract Background Two-stage reimplantation arthroplasty is one of the standard treatments for chronic periprosthetic joint infection (PJI). Scanty data exist regarding the risk factors for failure after two-stage reimplantation for periprosthetic hip infection. The purpose of this study was to investigate and identify the risk factors associated with failure after two-stage reimplantation hip arthroplasty. Methods Sixty-two patients with hip PJI treated with a two-stage reimplantation protocol at our institution from 2005 to 2012 were reviewed. Patients requiring medical treatment or reoperation for recurrent infection were defined as treatment failure. A multivariate Cox proportional hazards model was used to analyze the risk factors associated with treatment failure. Results Of the 62 patients, 11 (17.7%) patients had developed reinfection after the two-stage reimplantation with a mean follow-up of 5.7 years. The implant survival was 82.2% (95% confidence interval [CI] 75.19−92.55) at 10 years. Multivariate analysis revealed BMI ≥30 kg/m2 (hazard ratio [HR] 9.16; 95% CI 1.51−55.3; p = 0.0158), liver cirrhosis (HR 6.39; 95% CI 1.09−37.4; p = 0.0398), gram-negative organism (HR 5.68; 95% CI 1.18−27.4; p = 0.0303), and presence of sinus tract (HR 18.2; 95% CI 2.15−153; p = 0.0077) as the independent risk factors for treatment failure. Conclusions We found obesity, liver cirrhosis, gram-negative organism, and the presence of sinus tract were significantly related to the risks of failure after reimplantation arthroplasties.

Abstract Background Although the loss of bone mineral density (BMD) after total hip arthroplasty (THA) is a known problem, it remains unresolved. This study prospectively examined the effect of zoledronic acid (ZA) on bone turnover and BMD after cementless THA. Methods Between January 2010 and August 2011, 60 patients who underwent cementless THA were randomly assigned to receive either ZA infusion or placebo (0.9% normal saline only) postoperatively. ZA was administered at 2 day and 1 year postoperatively. Periprosthetic BMD in seven Gruen zones was assessed preoperatively and at given time points for 2 years. Serum markers of bone turnover, functional scales, and adverse events were recorded. Results Each group contained 27 patients for the final analysis. The loss of BMD across all Gruen zones (significantly in zones 1 and 7) up to 2 years postoperatively was noted in the placebo group. BMD was significantly higher in the ZA group than in the placebo group in Gruen zones 1, 2, 6, and 7 at 1 year and in Gruen zones 1, 6, and 7 at 2 years (p

This study tested the hypothesis that exposure to ambient fine particulate matter (PM2.5) pollution increased susceptibility of rat lung to damage from acute ischemia-reperfusion (IR) injury that was reversed by melatonin (Mel) treatment. Male-adult SD rats (n = 30) were categorized into group 1 (normal control), group 2 (PM2.5 only), group 3 (IR only at day 8 after PM2.5 exposure), group 4 (PM2.5 + IR) and group 5 (PM2.5 + IR + Mel), and all animals were sacrificed by day 10 after PM2.5 exposure. Oxygen saturation (%) was significantly higher in group 1 than in other groups and significantly lower in group 4 than in groups 2, 3 and 5 but it did not differ among the latter three groups (p

Background: The burden of osteoporosis in the Asia-Pacific region is not well characterized. The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study in the Asia-Pacific Region (MUSIC OS-AP) was designed to better understand the association of gastrointestinal events with patient-reported outcomes in postmenopausal women of this region. Methods: MUSIC OS-AP is a prospective, multinational, observational cohort study of postmenopausal women ≥50 years of age diagnosed with osteoporosis. The study was conducted in five Asia-Pacific countries: Australia, New Zealand, Taiwan, Korea, and India. MUSIC OS-AP has three components: a physician questionnaire, a retrospective chart review, and a prospective cohort study. The physician questionnaire investigated the role of gastrointestinal events in physicians' pharmacologic management of osteoporosis. The retrospective chart review, also completed by physicians, recorded rate of osteoporosis treatment and the types of osteoporosis medications prescribed to osteoporosis patients. The prospective cohort study investigated the associations between gastrointestinal events and patient-reported outcomes among patients taking oral medications for osteoporosis as well as reasons for non-treatment in patients who remained untreated. The prospective cohort study enrolled two groups of patients: untreated, and treated with oral osteoporosis medications. Untreated patients completed only the baseline surveys, providing information on gastrointestinal event rates, quality of life, health care resource use, and reasons for non-treatment. Treated patients, who were either new to osteoporosis medication or continuing an ongoing medication course, completed surveys at baseline and 3, 6, and 12 months post-baseline. The evaluations recorded patient characteristics, gastrointestinal events, health-related and osteoporosis-specific quality of life, health care resource use, medication adherence, and satisfaction with treatment. Results: Physicians at 59 sites completed the physician questionnaire, and data for 300 patients from 26 sites were abstracted for the retrospective chart review. Enrollment and baseline data collection for the prospective cohort study were conducted between July 2013 and August 2014 for 301 untreated and 3287 treated patients, of whom 1416 were new users and 1871 were experienced users of oral osteoporosis medications. Conclusions: The results of MUSIC OS-AP will highlight the association of gastrointestinal events with patient-reported outcomes among postmenopausal women with osteoporosis and elucidate physicians' management of gastrointestinal events among this patient population in the Asia-Pacific region.

Antibiotic-loaded polymethyl methacrylate (PMMA) has been widely applied in the treatment of knee periprosthetic joint infections. However, problems with antibiotic-loaded PMMA-based spacers, such as structural fracture and implant dislocation, remain unresolved. A novel polyethylene-based spacer, designed with an ultra-congruent articulating surface and multiple fenestrations, was introduced in the current study. Validation tests for biomechanical safety, wear performance, and efficacy of antibiotic cement were reported. During cycle fatigue testing, no tibial spacer failures were observed, and less wear debris generation was reported compared to commercial PMMA-based spacers. The volumetric wear of the novel spacer was within the safety threshold for osteolysis-free volumetric wear. An effective infection control was demonstrated despite the application of lesser antibiotic cement in the 30-day antibiotic elution test. The tube dilution test confirmed adequate inhibitory capabilities against pathogens with the loaded antibiotic option utilized in the current study. The novel polyethylene-based knee spacer may offer sufficient biomechanical safety and serve as an adequate carrier of antibiotic-loaded cement for infection control. Further clinical trials shall be conducted for more comprehensive validation of the novel spacer for practical application.

For total knee replacement (TKR) patients, rehabilitation after the surgery is key to regaining mobility. This study proposes a sensor-based system for effectively monitoring rehabilitation progress after TKR. The system comprises a hardware module consisting of the triaxial accelerometer and gyroscope, a microcontroller, and a Bluetooth module, and a software app for monitoring the motion of the knee joint. Three indices, namely the number of swings, the maximum knee flexion angle, and the duration of practice each time, were used as metrics to measure the knee rehabilitation progress. The proposed sensor device has advantages such as usability without spatiotemporal constraints and accuracy in monitoring the rehabilitation progress. The performance of the proposed system was compared with the measured range of motion of the Cybex isokinetic dynamometer (or Cybex) professional rehabilitation equipment, and the results revealed that the average absolute errors of the measured angles were between 1.65° and 3.27° for the TKR subjects, depending on the swing speed. Experimental results verified that the proposed system is effective and comparable with the professional equipment.

Background. This study was aimed at testing the association between the therapeutic efficacy of CD34+ cell treatment in patients with end-stage diffuse coronary artery disease as reflected in angiographic grading and results of directed in vivo angiogenesis assay (DIVAA) on their isolated peripheral blood mononuclear cell- (PBMC-) derived endothelial progenitor cells (EPCs). Methods. Angiographic grades (0: 75%) which presented the improvement of vessel density pre- and post-CD34+ treatment were given to 30 patients with end-stage diffuse coronary artery disease having received CD34+ cell treatment. The patients were categorized into low-score group (angiographic grade 0 or 1, n=12) and high-score group (angiographic grade 2 or 3, n=18). The percentages of circulating EPCs with KDR+/CD34+/CD45−, CD133+/CD34+/CD45−, and CD34+ were determined in each patient using flow cytometry. PBMC-derived EPCs from all patients were subjected to DIVAA through a 14-day implantation in nude mice. The DIVAA ratio (i.e., mean fluorescent units in angioreactors with EPCs/mean fluorescent units in angioreactors without EPCs) was obtained for each animal with implanted EPCs from each patient. Results and Conclusions. The number of EPCs showed no significant difference among the two groups. The DIVAA ratio in the high-score group was significantly higher than that in the low-score group (p=0.0178). Logistic regression revealed a significant association between the DIVAA ratio and angiographic grading (OR 3.12, 95% CI: 1.14–8.55, p=0.027). The area under the ROC curve (AUC) was 0.8519 (p=0.0013). We proposed that DIVAA may be a reliable tool for assessing coronary vascularization after CD34+ cell treatment.

This study tested the hypothesis that shock wave therapy (SW) enhances mitochondrial uptake into the lung epithelial and parenchymal cells to attenuate lung injury from acute respiratory distress syndrome (ARDS). ARDS was induced in rats through continuous inhalation of 100% oxygen for 48 h, while SW entailed application 0.15 mJ/mm2 for 200 impulses at 6 Hz per left/right lung field. In vitro and ex vivo studies showed that SW enhances mitochondrial uptake into lung epithelial and parenchyma cells (all p

Introduction: There has been a debate on the use of ceramic-on-ceramic coupling with the retained femoral stem in isolated acetabular revision. The purpose of this study was to retrospectively review the results and complications of isolated revision of the acetabular component using alumina-on-alumina bearings. Methods: Between August 2010 and December 2013, 22 patients (23 hips) with a mean age of 60.74 years (40–73) underwent isolated revision of the acetabular component from metal-on-polyethylene to alumina-on-alumina bearings without using a metal sleeve on the undamaged trunnion. All patients completed clinical and radiographic evaluation. Results: At a mean follow-up of 3 years (2–5.5), all patients had a significant improvement in the clinical outcome, including Harris Hip Score (84.9 vs. 43, p < 0.001), West Ontario McMaster University Osteoarthritis Index Score (14.4 vs. 49.2, p < 0.001), and visual analogue pain score (1.42 vs. 6.63, p < 0.001). Complications included one aseptic loosening of the acetabular component and three noisy hips (click only). No fracture of the ceramic bearings, dislocation, infection, or squeaking noise were observed in any of the patients. Conclusion: Isolated revision of the acetabular component to alumina-on-alumina bearings on the undamaged trunnion may be considered if there is no available titanium sleeves. Our study showed a satisfactory early outcome with minimal complications. However, a longer term follow-up study is necessary.

We hypothesized that the effect of hyperbaric oxygen (HBO) on bone formation is increased via osteogenic differentiation of bone marrow stromal cells (BMSCs), which is regulated by Wnt3a/β-catenin signaling. Our in vitro data showed that HBO increased cell proliferation, Wnt3a production, LRP6 phosphorylation, and cyclin D1 expression in osteogenically differentiated BMSCs. The mRNA and protein levels of Wnt3a, β-catenin, and Runx2 were upregulated while those of GSK-3β were downregulated after HBO treatment. The relative density ratio (phospho-protein/protein) of Akt and GSK-3β was both up-regulated while that of β-catenin was down-regulated after HBO treatment. We next investigated whether HBO affects the accumulation of β-catenin. Our Western blot analysis showed increased levels of translocated β-catenin that stimulated the expression of target genes after HBO treatment. HBO increased TCF-dependent transcription, Runx2 promoter/Luc gene activity, and the expression of osteogenic markers of BMSCs, such as alkaline phosphatase activity, type I collagen, osteocalcin, calcium, and the intensity of Alizarin Red staining. HBO dose dependently increased the bone morphogenetic protein (BMP2) and osterix production. We further demonstrated that HBO increased the expression of vacuolar-ATPases, which stimulated Wnt3a secretion from BMSCs. Finally, we showed that the beneficial effects of HBO on bone formation were related to Wnt3a/β-catenin signaling in a rabbit model by histology, mechanical testing, and immunohistochemical assays. Accordingly, we concluded that HBO increased the osteogenic differentiation of BMSCs by regulating Wnt3a secretion and signaling.

In the original publication of this article [1], the first name of the 5th author is wrong.

The diagnosis of periprosthetic joint infection is sometimes straightforward with purulent discharge from the fistula tract communicating to the joint prosthesis. However it is often difficult to differentiate septic from aseptic loosening of prosthesis because of the high culture-negative rates in conventional microbiologic culture. This study used quantitative reverse transcription polymerase chain reaction (RT-qPCR) to amplify bacterial 16S ribosomal RNA in vitro and in 11 clinical samples. The in vitro analysis demonstrated that the RT-qPCR method was highly sensitive with the detection limit of bacterial 16S rRNA being 0.148 pg/μl. Clinical specimens were analyzed using the same protocol. The RT-qPCR was positive for bacterial detection in 8 culture-positive cases (including aerobic, anaerobic, and mycobacteria) and 2 culture-negative cases. It was negative in one case that the final diagnosis was confirmed without infection. The molecular diagnosis of bacterial infection using RT-qPCR to detect bacterial 16S rRNA around a prosthesis correlated well with the clinical findings. Based on the promising clinical results, we were attempting to differentiate bacterial species or drug-resistant strains by using species-specific primers and to detect the persistence of bacteria during the interim period before the second stage reimplantation in a larger scale of clinical subjects.

Periprosthetic joint infection is devastating and increases medical expenditure and socioeconomic burden. Antibiotic-loaded cement spacer is useful in the interim period before the reimplantation surgery. Prefabricated antibiotic-loaded cement spacers can decrease operation time but have been limitedly used clinically. In the literature, there is no clear recommendation on the storage temperature for the prefabricated cement spacers. We used an in vitro model to analyze whether the storage temperature at 25°C, 4°C, or −20°C for 2 weeks or 3 months could affect the release of vancomycin from the cement. We found that the storage temperature and time had no significant effects on the pattern and amount of vancomycin release. The patterns of vancomycin release from the cement stored at different temperatures were similar with an abrupt release in the first 3 days and steadily declined in the following period. This study provides a preliminary result to justify the storage of fabricating antibiotic-loaded cement spacer sterilely packed at room temperature. Further studies to examine the effects of storage temperature on the mechanical strength and the release pattern of other antibiotics should be done to provide more evidence to support the clinical use of prefabricated ready-to-use antibiotic-loaded cement spacer.

Background: Tibial eminence avulsion fracture often co-occurs with tibial plateau fracture, which leads to difficult concomitant management. The value of simultaneous arthroscopy-assisted treatment continues to be debated despite its theoretical advantages. We describe a simple arthroscopic suture fixation technique and hypothesize that simultaneous treatment is beneficial.Methods: Patients with a tibial eminence avulsion fracture and a concurrent tibial plateau fracture who underwent simultaneous arthroscopically assisted treatment between 2005 and 2008 were enrolled in this retrospective study. Second-look arthroscopic evaluation and Rasmussen scores of clinical and radiographic parameters were used to assess simultaneous treatment.Results: Forty-one patients (41 knees) met the inclusion criteria. All 41 fractures were successfully united. All patients had side-to-side differences of less than 3 mm and negative findings in Lachman and pivot-shift tests at their final follow-up. The mean postoperative Rasmussen clinical score was 27.3 (range: 19-30), and the mean radiologic score was 16.5 (range: 12-18). Clinical and radiographic outcomes in 98 % of the patients were good or excellent. There were no complications directly associated with arthroscopy in any patient.Conclusions: Simultaneous arthroscopic suture fixation of associated tibial eminence avulsion fracture did not interfere with the plates and screws used to stabilize the tibial plateau fracture. It gave the knee joint adequate stability, minimal surgical morbidity, and satisfactory radiographic and clinical outcomes in a minimum follow-up of 5 years and in the arthroscopic second-look assessments. [ABSTRACT FROM AUTHOR]

Background: Accurate femoral rotational alignment is of vital importance for successful total knee arthroplasty (TKA). The value of computer-assisted surgery TKA (CAS-TKA) in increasing the accuracy of femoral rotational alignment remains controversial. We hypothesize that outcomes are related to the severity of preoperative varus and valgus deformity and that CAS-TKA may be beneficial under certain circumstances. Methods: Between January 2007 and December 2013, patients with osteoarthritis and varus angulation in the mechanical axis (MA) ≥ 15° and valgus angulation in the MA ≥ 10° (based on hip-to-ankle standing radiography) who underwent TKA were divided into four groups. CAS-TKA and conventional TKA outcomes were compared in patients who had preoperative advanced genu varum and advanced genu valgum deformities. The accuracy of component alignment and postoperative limb alignment was determined using radiographic parameters and computed tomography (CT). Results: One hundred and eight patients (144 knees) were included in the analysis. For patients with preoperative advanced genu varum deformity, a significant difference was detected in the sagittal femoral angle (p < 0.001), but no significant improvement of femoral rotational alignment was noted (p = 0.127). In patients with preoperative advanced genu valgum deformity, a significant difference was found in the sagittal femoral angle (p = 0.034). The femoral rotational angle was significantly closer to the proper position in the CAS-TKA group (p < 0.001). When comparing the percentage of knees achieving the proper alignment, there was a decrease in the amount of outlier for the femoral rotational angle for CAS-TKA in advanced genu valgum deformity (p = 0.011). Conclusions: Our data demonstrate that CAS-TKA is beneficial in obtaining proper femoral rotational alignment in patients with advanced genu valgum deformity (preoperative MA ≥ 10° valgus). In patients with advanced genu varum deformity (preoperative MA ≥ 15° varus), CAS-TKA did not improve the femoral rotational alignment. [ABSTRACT FROM AUTHOR]

Background: A two-stage revision is a well-accepted method for the treatment of a deep infection of a hip with a joint implant. In the present study, the results associated with the interim use of antibiotic-loaded cement beads were compared with those associated with the interim use of an antibiotic-loaded cement prosthesis. Methods: One hundred and twenty-eight consecutive patients who were managed with a two-stage revision hip arthroplasty for the treatment of an infection were followed clinically and radiographically for an average of 4.9 years. Cement beads were implanted following resection arthroplasty in the first seventy hips, and a custom cement pros- thesis was implanted in the subsequent fifty-eight hips. Results: There was no evidence of recurrent infection in 122 patients (95.3%); the infection-free rates in both groups were similar. The use of a spacer prosthesis was associated with a higher hip score, a shorter hospital stay, and better walking capacity in the interim period; a decreased operative time, less blood loss, and a lower transfusion requirement at the time of reimplantation; and fewer postoperative dislocations. Conclusions: The present study supports the safety and efficacy of the routine use of an antibiotic-loaded cement prosthesis in the interim between the stages of a two-stage revision procedure for the treatment of an infection at the site of a hip arthroplasty. Level of Evidence: Therapeutic study, Level III-2 (retrospective cohort study). See Instructions to Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

BackgroundTotal hip replacement (THR) is considered the gold standard of treatment for refractory degenerative hip disorders. Identifying patients who should receive THR in the short term is important. Some conservative treatments, such as intra-articular injection administered a few months before THR, may result in higher odds of arthroplasty infection. Delayed THR after functional deterioration may result in poorer outcomes and longer waiting times for those who have been flagged as needing THR. Deep learning (DL) in medical imaging applications has recently obtained significant breakthroughs. However, the use of DL in practical wayfinding, such as short-term THR prediction, is still lacking. ObjectiveIn this study, we will propose a DL-based assistant system for patients with pelvic radiographs to identify the need for THR within 3 months. MethodsWe developed a convolutional neural network–based DL algorithm to analyze pelvic radiographs, predict the hip region of interest (ROI), and determine whether or not THR is required. The data set was collected from August 2008 to December 2017. The images included 3013 surgical hip ROIs that had undergone THR and 1630 nonsurgical hip ROIs. The images were split, using split-sample validation, into training (n=3903, 80%), validation (n=476, 10%), and testing (n=475, 10%) sets to evaluate the algorithm performance. ResultsThe algorithm, called SurgHipNet, yielded an area under the receiver operating characteristic curve of 0.994 (95% CI 0.990-0.998). The accuracy, sensitivity, specificity, and F1-score of the model were 0.977, 0.920, 0932, and 0.944, respectively. ConclusionsThe proposed approach has demonstrated that SurgHipNet shows the ability and potential to provide efficient support in clinical decision-making; it can assist physicians in promptly determining the optimal timing for THR.

BackgroundThe aim of this prospective study was to use direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to rapidly diagnose periprosthetic joint infections (PJIs).MethodSynovial fluid was taken from 77 patients (80 joints, 41 hips and 39 knees) who met the International Consensus Meeting criteria for PJI, and inoculated into blood culture bottles (BCBs) and onto conventional swabs. Positive blood cultures were analyzed using either direct or routine MALDI-TOF MS. Pathogen identification and the time to identification was recorded. Differences between groups were analyzed using the Kruskal-Wallis test and Bonferroni's post-hoc test.ResultsDirect and routine MALDI-TOF MS both detected 64 positive results (80%), compared to 47 (59%) by conventional swabs (p = 0.002). Direct MALDI-TOF MS identified 85.3% of the gram-positive organisms and 92.3% of the gram-negative organisms. No fungi were identified by direct MALDI-TOF MS. In 17 BCBs that were flagged positive, identification by direct MALDI-TOF MS failed. Among the positive results in the direct MALDI-TOF MS group, Staphylococcus aureus accounted for 47%, followed by Staphylococcus epidermidis (17%), Escherichia coli (9%) and Klebsiella pneumoniae (9%). The median time to microorganism identification was significantly shorter with direct MALDI-TOF MS (12.7 h, IQR: 8.9-19.6 h) than with routine MALDI-TOF MS (39.5 h, IQR: 22.8-46.0 h) or swabs (44.4 h, IQR: 27.2-72.6 h) (p < 0.0001). In pairwise comparisons, there were significant differences in the time of microorganism identification between direct MALDI-TOF MS and routine MALDI-TOF MS (p < 0.0001) or swab culture (p < 0.0001). There was no significant difference between routine MALDI-TOF MS and swab culture (p = 0.0268).ConclusionCompared with current laboratory practice, direct MALDI-TOF MS shortened the time to microorganism identification and had superior results compared to conventional swabs, except for fungi. Further studies should investigate whether the earlier administration of appropriate antimicrobial agents can improve the treatment outcomes of PJIs.

Abstract Although low-energy shock wave (SW) is adopted to treat ischemic diseases because of its pro-angiogenic properties, the underlying mechanism remains unclear. This study is aimed at testing whether SW-induced angiogenesis may be through endothelial vascular endothelial growth factor receptor 2 (VEGFR2) signaling and trafficking. Phosphorylation of VEGFR2-Akt-eNOS axis and production of nitric oxide (NO) were determined in human umbilical vein endothelial cells (HUVECs) treated with SW. Carotid artery in ob/ob mice was treated with SW before evaluation with sprouting assay. Critical limb ischemia was induced in ob/ob mice to evaluate blood flow recovery post-SW treatment. Tube formation and migration assays were also performed with/without SW treatment in the presence/absence of SU5416 (VEGFR2 kinase inhibitor) and siRNA-driven silencing of VEGFR2. Chloroquine was used for disrupting endosome, and Rab11a controlling slow endocytic recycling was silenced with siRNA in vitro. Following SW treatment, augmented ligand-independent phosphorylation in VEGFR2-Akt-eNOS axis and endogenous NO production, increased cellular migration and tube formation and elevated sprouting of carotid artery and blood flow in ischemic limb in ob/ob mice were noted. Moreover, SU5416 and VEGFR2 silencing both inhibited SW-induced angiogenesis. SW-induced angiogenesis, accompanied by increased VEGFR2 protein expression without transcriptional change, was suppressed by chloroquine and Rab11a silencing. We concluded that SW enhanced angiogenesis via ligand-independent activation of VEGFR2 and further prolonged angiogenesis through endosome-to-plasma membrane recycling in endothelial cells.

Background: Osteonecrosis of the femoral head can lead to destruction of the hip joint and disabling arthritis in young adults, if left untreated. Among the salvage procedures, core decompression combined with bone graft substitutes is a viable option for joint preservation. The purpose of this study was to review the outcomes of using synthetic bone graft substitute (calcium sulfate and calcium phosphate) for the treatment of late-stage osteonecrosis of the femoral head. Methods: From November 2008 to May 2009, 19 hips in 18 patients with osteonecrosis of the femoral head [6 hips in Association Research Circulation Osseous (ARCO) stage IIC and 13 hips in stage IIIA] were treated with core decompression combined with PRO-DENSE™ (Injectable Regenerative Graft). The average age of the patients at the time of surgery was 48 years (range 25-67 years). Twelve patients (13 hips) overused alcohol, four patients (4 hips) were idiopathic, one patient (1 hip) used corticosteroids, and one patient (1 hip) was post-traumatic. The clinical failure was defined as conversion to total hip arthroplasty or progression in head collapse. Results: At the conclusion of the study, 3 in the 6 stage IIC hips and 8 in the 13 stage IIIA hips were converted to total hip arthroplasty in an average of 8.5 months (range 4-30 months) postoperatively. Advanced collapse of the femoral head awaiting for total hip arthroplasty was observed in the other six hips. Of the 19 hips, only 2 hips (10.5%) survived without further collapse in the 5-year follow-up. This resulted in 89.5% failure rate with early resorption of the grafting in an average of 5.3 months. Conclusions: Core decompression combined with an injectable calcium sulfate and calcium phosphate composite graft (PRO-DENSE) were associated high failure rates in the early postoperative period. It is not recommended for the treatment of ARCO stage IIC and IIIA osteonecrosis of the femoral head.

Staphylococcus aureus (S. aureus) is one of the most common causes of biofilm infections in periprosthetic joint infections (PJIs). Accumulating evidence has shown that the immunosuppressive environment established by S. aureus biofilm infection in PJIs involves the presence of myeloid-derived suppressor cells (MDSCs) and M2-macrophages. Due to the diversity of MDSCs, little is known about whether S. aureus biofilm preferentially expands specific MDSC subsets or whether MDSCs can further differentiate into M2-macrophages during S. aureus biofilm infection. Here, we show that in agreement with the results from an established rat PJI model, S. aureus biofilm cocultured with freshly isolated bone marrow cells (BMCs) in vitro significantly increases the proportions of MDSCs, total macrophages and M2-macrophages. Interestingly, we find that treatment of the BMCs in vitro with S. aureus biofilm preferentially promotes the expansion of monocytic MDSCs but not granulocytic MDSCs. Biofilm treatment also substantially enhances the overall MDSC immunosuppressive activity in addition to the MDSC expansion in vitro. Importantly, we provide evidence that S. aureus biofilm is capable of further stimulating the conversion of monocytic MDSCs into M2-macrophages in vitro and in vivo. Collectively, our studies reveal a direct link between MDSCs and M2-macrophages occurring in S. aureus-associated PJIs.

BACKGROUND:Vibrio vulnificus necrotizing skin and soft tissue infections (VNSSTIs) usually predispose patients with or without preexisting liver disease to septic shock, and then evolve to multiple organ dysfunction syndrome (MODS), thus resulting in high mortality in humans. However, clinicians do not have a valid prediction model to provide a reliable estimate of case-fatality rate when caring for these acutely and/or critically ill patients. METHODS/PRINCIPAL FINDINGS:We retrospectively analyzed 39 consecutive patients with VNSSTIs (mean age: 65.7 ± 11.3 years) at our institution between 2007 and 2010. All patients were treated with the same protocol. Demographic and clinical characteristics, disease severity on admission, treatment details, and outcomes were collected for each patient and extracted for analyses. We studied the predictive value of the model for end-stage liver disease (MELD), modified MELD including sodium (MELD-Na), and laboratory risk indicator for necrotizing fasciitis (LRINEC) scores for case-fatality. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. The mean MELD, MELD-Na and LRINEC scores on admission were 15.1 ± 1.1, 17.7 ± 1.1, and 3.4 ± 0.4 points, respectively. After admission, these patients had temporary or progressive deterioration of nearly all their scores and lab values. The area under the ROC curve for the MELD and ΔMELD scoring models were 0.929 (p = 0.002) and 0.897 (p = 0.005), respectively. An optimal MELD/ΔMELD cutoff value ≥ 20/2 had a good sensitivity and specificity (all > 80%), with a 64/13-fold increased odds for case-fatality. Additionally, the development of severe forms of anemia (p = 0.014) and hypoalbuminemia (p = 0.019) were associated with an increased case-fatality rate. DISCUSSION:The MELD/ΔMELD scoring model is an effective risk stratification indicator at the time of admission and also an excellent condition monitor during hospitalization for medical care of acutely and/or critically ill patients with VNSSTIs.

Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (87.6%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.62; 95% confidence interval: 1.44-14.8) of having coagulation abnormalities than did those without the mutation (wild-type) (χ(2) p = 0.006). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head.