The cementless taper wedge vs. fit-and-fill stem in primary total hip arthroplasty: risk of stem-related complication differs across Dorr types.

INTRODUCTION: The choice between a cementless taper wedge stem and a fit-and-fill stem in total Hip arthroplasty (THA) for various proximal femoral morphological types has not been thoroughly evaluated. This study aimed to compare the risk of stem-related complications between these two stem types in Dorr type A, B, and C femurs. MATERIALS AND METHODS: From January 2015 through April 2021, we retrospectively reviewed 1995 cementless THA procedures. We stratified all procedures into three groups: Dorr type A (N = 360, 18.0%), B (N = 1489, 74.7%) and C (N = 146, 7.3%). The primary outcome domain was stem-related complications, including stem subsidence ≥ 3 mm, intraoperative fracture, periprosthetic fracture and aseptic stem loosening. We performed multivariate regression analysis to compare the risk of stem-related complication between the two stem types. Other factors included age, sex, body mass index, diagnosis, age-adjusted Charlson comorbidity index, stem alignment and canal fill ratio. RESULTS: The incidence of stem-related complications in the taper wedge and fit-and-fill stem groups was 4.4% (N = 15) and 6.5% (N = 107), respectively. Fit-and-fill stems showed an increased risk of stem-related complications (aOR: 9.903, 95% CI: 1.567-62.597) only in Dorr type C femurs. No significant difference in risk was observed in Dorr type A and B femurs. Furthermore, the canal fill ratio at the lesser trochanter, 2 cm and 7 cm below the lesser trochanter, did not exhibit an association with stem-related complications in any Dorr type. CONCLUSIONS: Concerning the risk of stem-related complications, the taper wedge stem was a better choice in Dorr type C femurs. However, there was no difference in risk between the taper wedge stem and fit-and-fill stem in Dorr type A and B femurs.

Body constitutions of traditional Chinese medicine caused a significant effect on irritable bowel syndrome.

BACKGROUND: According to the theory of traditional Chinese medicine (TCM), all types of body constitutions, except for the Gentleness (ie, the control group in our study), have disease susceptibility and affect the disease development process. This study attempted to investigate the relationship between TCM body constitutions and irritable bowel syndrome (IBS). METHODS: This cross-sectional study was based on Taiwan Biobank (TWB) and collected clinical data from 13 941 subjects aged 30 to 70. The results of the study showed that subjects with Yang-deficiency (N = 3161 subjects, odds ratio [OR] = 2.654, 95% CI = 1.740-3.910), Ying-deficiency (N = 3331 subjects, OR = 1.096, 95% CI = 0.627-1.782) or Stasis (N = 2335 subjects, OR = 1.680, 95% CI = 0.654-3.520) were more likely to have IBS. RESULTS: If the subjects with two or more TCM body constitutions: Yang-deficiency + Ying-deficiency (OR = 3.948, 95% CI = 2.742-5.560), Yang-deficiency + Stasis (OR = 2.312, 95% CI = 1.170-4.112), Ying-deficiency + Stasis (OR = 1.851, 95% CI = 0.828-3.567), or Yang-deficiency + Ying-deficiency + Stasis (OR = 3.826, 95% CI = 2.954-4.932) were also prone to IBS. CONCLUSION: These results confirmed the high correlation between TCM body constitutions and IBS. Because the current treatment for IBS is not entirely satisfactory, integrated traditional Chinese and Western medicine might provide patients with an alternative treatment option to alleviate IBS.

Risk factors for venous thromboembolism after primary total joint arthroplasty: An analysis of 7511 Taiwanese patients.

BACKGROUND: The need for thromboprophylaxis in Asian patients after primary total joint arthroplasty (TJA) remains inconclusive. We aimed to identify the risk factors for venous thromboembolism (VTE) events following primary TJA in a Taiwanese population. METHODS: From January 2010 to December 2019, we studied 7511 patients receiving primary TJA from a single surgeon. We validated the incidence and risk factors for 30- and 90-day symptomatic VTE events, including age, sex, body mass index (BMI), smoking, medical comorbidities, VTE history, presence of varicose veins, total knee arthroplasty (TKA) vs total hip arthroplasty (THA), unilateral vs bilateral procedure and receipt of VTE prophylaxis, transfusion, and length of stay. RESULTS: The incidence of 30- and 90-day symptomatic VTE events was 0.33% and 0.44%, respectively. Multivariate regression analysis showed that BMI ≥30 (adjusted odds ratio (aOR): 4.862, 95% CI, 1.776-13.313), bilateral TJA procedure (aOR: 2.665, 95% CI, 1.000-7.104), and presence of varicose veins (aOR: 9.946, 95% CI, 1.099-90.024) were associated with increased odds of 30-day symptomatic VTE events. Age ≥77 years (aOR, 2.358, 95% CI, 1.034-5.381) and BMI ≥30 (aOR: 2.832, 95% CI, 1.039-7.721) were associated with increased odds of 90-day symptomatic VTE events. CONCLUSION: Age ≥77 years, BMI ≥30, bilateral TJA procedure, or presence of varicose veins may require pharmacological thromboprophylaxis because such patients have a higher risk of VTE after primary TJA.

Efficient induction of pluripotent stem cells differentiated into mesenchymal stem cell lineages.

BACKGROUND: Mesenchymal stem cells (MSCs) have garnered significant attention in the field of cell-based therapy owing to their remarkable capabilities for differentiation and self-renewal. However, primary tissue-derived MSCs are plagued by various limitations, including constrained tissue sources, arduous and invasive retrieval procedures, heterogeneous cell populations, diminished purity, cellular senescence, and a decline in self-renewal and proliferative capacities after extended expansion. Addressing these challenges, our study focuses on establishing a robust differentiation platform to generate mesenchymal stem cells derived from induced pluripotent stem cells (iMSCs). METHODS: To achieve this, we used a comprehensive methodology involving the differentiation of induced pluripotent stem cells into MSCss. The process was meticulously designed to ensure the expression of key MSC positive markers (CD73, CD90, and CD105) at elevated levels, coupled with the minimal expression of negative markers (CD34, CD45, CD11b, CD19, and HLA-DR). Moreover, the stability of these characteristics was evaluated across 10th generations. RESULTS: Our findings attest to the success of this endeavor. iMSCs exhibited robust expression of positive markers and limited expression of negative markers, confirming their MSC identity. Importantly, these characteristics remained stable even up to the 10th generation, signifying the potential for sustained use in therapeutic applications. Furthermore, our study demonstrated the successful differentiation of iMSCs into osteocytes, chondrocytes, and adipocytes, showcasing their multilineage potential. CONCLUSION: In conclusion, the establishment of induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) presents a significant advancement in overcoming the limitations associated with primary tissue-derived MSCs. The remarkable stability and multilineage differentiation potential exhibited by iMSCs offer a strong foundation for their application in regenerative medicine and tissue engineering. This breakthrough paves the way for further research and development in harnessing the full therapeutic potential of iMSCs.

Safety and Tolerability of Intra-Articular Injection of Adipose-Derived Mesenchymal Stem Cells GXCPC1 in 11 Subjects With Knee Osteoarthritis: A Nonrandomized Pilot Study Without a Control Arm.

The current study aimed to determine the safety profile of intra-articular-injected allogeneic adipose-derived mesenchymal stem cells (ADSCs) GXCPC1 in subjects with knee osteoarthritis (OA) and its preliminary efficacy outcome. The 3 + 3 phase I study was designed with two dose-escalation cohorts: low dose (6.7 × 106 GXCPC1, N = 5) and high dose (4 × 107 GXCPC1, N = 6). The primary endpoint was safety, which was evaluated by recording adverse events throughout the trial; the secondary endpoints included total, pain, stiffness, and function subscales of the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and 12-Item Short Form (SF-12) health survey questionnaire. The GXCPC1 treatment was found to be safe after 1 year of follow-up with no treatment-related severe adverse events observed. When compared to baseline, subjects in both the low- and high-dose cohorts demonstrated improving trends in pain and knee function after receiving GXCPC1 treatment. Generally, the net change in pain (95% confidence interval (CI) = -7.773 to -2.561t at 12 weeks compared to baseline) and knee function (95% CI = -24.297 to -10.036t at 12 weeks compared to baseline) was better in subjects receiving high-dose GXCPC1. Although this study included a limited number of subjects without a placebo arm, it showed that the intra-articular injection of ADSCs was safe and well-tolerated in subjects with therapeutic alternatives to treat knee OA. However, a larger scale study with an appropriate control would be necessary for clinical efficacy in the following study.

Perioperative complications of using freezing nitrogen ethanol composite to treat bone tumors: Clinical experience from a single center.

BACKGROUND: The cryoablation efficacy of semisolid freezing nitrogen ethanol composite (FNEC) has been demonstrated. We aimed to investigate the feasibility of adjuvant FNEC-assisted cryoablation in different bone cavity types by assessing the perioperative complication rates. METHODS: The medical charts of patients who received intraoperative adjuvant cryoablation using semisolid FNEC for bone tumors from December 2013 to January 2018 were reviewed. The bone cavities were categorized into three types according to liquid spill potential (type 1, able to hold liquid without limb manipulation; type 2, required extensive limb manipulation to retain liquid; type 3, unable to retain liquid). The overall complication rate and the complication rates stratified by bone cavity type were determined. RESULTS: Among the 76 patients, 30.3%, 57.9%, and 11.8% had type 1, 2, and 3 bone cavities, respectively. The mean follow-up time for perioperative complications was 43.5 ± 24.1 days. Five patients experienced complications, including two cases of skin damage, two cases of skin infection, and one case of fracture, yielding an overall perioperative complication rate of 6.4%. All cases of skin damage and skin infection were superficial and manageable by oral antibiotics. The patient with a pathologic fracture recovered well after being treated with open reduction and plate fixation. No neuropraxia was noted within the first few days postsurgery in any patient. The complication rates in type 1, 2, and 3 bone cavities were 13%, 4.6%, and 0%, respectively. CONCLUSION: All bone cavity types had a low incidence of perioperative complications after treatment with adjuvant FNEC-assisted cryoablation. Semisolid FNEC-assisted cryoablation is a feasible alternative to overcome the liquid spill potential in bone cavities resulting from tumor resection and intralesional curettage.

Overcoming the challenges of scalable iPSC generation in translation medicine.

BACKGROUND: The potential of induced pluripotent stem cells (iPSCs) in revolutionizing regenerative medicine cannot be overstated. iPSCs offer a profound opportunity for therapies involving cell replacement, disease modeling, and cell transplantation. However, the widespread application of iPSC cellular therapy faces hurdles, including the imperative to regulate iPSC differentiation rigorously and the inherent genetic disparities among individuals. To address these challenges, the concept of iPSC super donors emerges, holding exceptional genetic attributes and advantageous traits. These super donors serve as a wellspring of standardized, high-quality cell sources, mitigating inter-individual variations and augmenting the efficacy of therapy. METHODS: In pursuit of this goal, our study embarked on the establishment of iPSC cell lines specifically sourced from donors possessing the HLA type (A33:03-B58:01-DRB1*03:01). The reprogramming process was meticulously executed, resulting in the successful generation of iPSC lines from these carefully selected donors. Subsequently, an extensive characterization was conducted to comprehensively understand the features and attributes of these iPSC lines. RESULTS: The outcomes of our research were highly promising. The reprogramming efforts culminated in the generation of iPSC lines from donors with the specified HLA type. These iPSC lines displayed a range of distinctive characteristics that were thoroughly examined and documented. This successful generation of iPSC lines from super donors possessing advantageous genetic traits represents a significant stride towards the realization of their potential in therapeutic applications. CONCLUSION: In summary, our study marks a crucial milestone in the realm of regenerative medicine. The establishment of iPSC lines from super donors with specific HLA types signifies a paradigm shift in addressing challenges related to iPSC cellular therapy. The standardized and high-quality cell sources derived from these super donors hold immense potential for various therapeutic applications. As we move forward, these findings provide a solid foundation for further research and development, ultimately propelling the field of regenerative medicine toward new horizons of efficacy and accessibility.

Recent advances in the diagnosis and management of acute myocardial infarction.

With the discovery of new biomarkers for the early detection of acute myocardial infarction (AMI), advancements in valid medication, and percutaneous coronary intervention (PCI), the overall prognosis of AMI has improved remarkably. Nevertheless, challenges remain which require more difficult work to overcome. Novel diagnostic and therapeutic techniques include new AMI biomarkers, hypothermia therapy, supersaturated oxygen (SSO 2 ) therapy, targeted anti-inflammatory therapy, targeted angiogenesis therapy, and stem cell therapy. With these novel methods, we believe that the infarction size after AMI will decrease, and myocardial injury-associated ventricular remodeling may be avoided. This review focuses on novel advances in the diagnosis and management of AMI.

Klotho Overexpression Is Frequently Associated With Upstream Rearrangements in Fusion-Negative Phosphaturic Mesenchymal Tumors of Bone and Sinonasal Tract.

Phosphaturic mesenchymal tumors (PMT) are uncommon neoplasms that cause hypophosphatemia/osteomalacia mainly by secreting fibroblast growth factor 23. We previously identified FN1::FGFR1/FGF1 fusions in nearly half of the PMTs and frequent KL (Klotho or α-Klotho) overexpression in only those with no known fusion. Here, we studied a larger cohort of PMTs for KL expression and alterations. By FN1 break-apart fluorescence in situ hybridization (FISH) and reappraisal of previous RNA sequencing data, 6 tumors previously considered "fusion-negative" (defined by negative results of FISH for FN1::FGFR1 fusion and FGF1 break-apart and/or of RNA sequencing) were reclassified as fusion-positive PMTs, including 1 containing a novel FN1::ZACN fusion. The final cohort of fusion-negative PMTs included 33 tumors from 32 patients, which occurred in the bone (n = 18), soft tissue (n = 10), sinonasal tract (n = 4), and brain (n = 1). In combination with previous work, RNA sequencing, RNA in situ hybridization, and immunohistochemistry showed largely concordant results and demonstrated KL/α-Klotho overexpression in 17 of the 28 fusion-negative and none of the 10 fusion-positive PMTs studied. Prompted by a patient in this cohort harboring germline KL upstream translocation with systemic α-Klotho overexpression and multifocal PMTs, FISH was performed and revealed KL rearrangement in 16 of the 33 fusion-negative PMTs (one also with amplification), including 14 of the 17 cases with KL/α-Klotho overexpression and none of the 11 KL/α-Klotho-low fusion-negative and 11 fusion-positive cases studied. Whole genomic sequencing confirmed translocation and inversion in 2 FISH-positive cases involving the KL upstream region, warranting further investigation into the mechanism whereby these rearrangements may lead to KL upregulation. Methylated DNA immunoprecipitation and sequencing suggested no major role of promoter methylation in KL regulation in PMT. Interestingly, KL-high/-rearranged cases seemed to form a clinicopathologically homogeneous group, showing a predilection for skeletal/sinonasal locations and typically matrix-poor, cellular solitary fibrous tumor-like morphology. Importantly, FGFR1 signaling pathways were upregulated in fusion-negative PMTs regardless of the KL status compared with non-PMT mesenchymal tumors by gene set enrichment analysis, perhaps justifying FGFR1 inhibition in treating this subset of PMTs.

Combination of enoxaparin and low-dose aspirin for thromboprophylaxis in selective patients after primary total joint arthroplasty in a Taiwanese population.

BACKGROUND: The incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) after total joint arthroplasty (TJA) procedures are lower in Asian populations than in Caucasian populations. Therefore, the need for thromboprophylaxis in Asian patients undergoing TJA remains inconclusive. The aim of this study was to validate the clinical outcomes of thromboprophylaxis in selective TJA patients in a Taiwanese population. METHODS: We retrospectively reviewed records of patients who underwent TJA procedures performed by a single-surgeon between January 2010 through December 2019. Patients received thromboprophylaxis with a combination of enoxaparin and low-dose aspirin if they fulfilled any of the following criteria: 1) body mass index >30 (kg/m 2 ), 2) presence of varicose veins, 3) history of DVT or PE, or 4) simultaneous bilateral TJA procedure. We assessed the incidence of DVT and PE, 90-day postoperative complications, length of stay, in-hospital mortality, 30-day and 90-day readmission, and 1-year reoperation. RESULTS: Of the 7511 patients included in this study, 2295 (30.6%) patients received thromboprophylaxis. For patients who received thromboprophylaxis(N = 2295), the incidence of DVT and PE were 0.44% and 0%, respectively. For patients who did not receive thromboprophylaxis (N = 5216), the incidence of DVT and PE was 0.46% and 0.04%, respectively. The overall rates of 90-day postoperative complications (2.3%), 30-day (1.8%) and 90-day readmission (2.3%), and 1-year reoperation (1.1%) were low. CONCLUSION: Providing thromboprophylaxis for selective TJA patients within the Taiwanese population was effective, as indicated by the low incidence of DVT and PE. Complications, such as surgical site infection, should be carefully weighed and managed.

Efficacy and safety of once-daily prolonged-release tacrolimus versus twice-daily tacrolimus in kidney transplant recipients: A meta-analysis and trial sequential analysis.

BACKGROUND: Kidney transplantation is the most important treatment for end-stage renal disease. Immunosuppressive therapies can prevent acute rejection for kidney transplant recipients. Tacrolimus is usually administered to prevent graft rejection after transplantation. Previous studies have indicated that once-daily tacrolimus may improve medication adherence. Therefore, this meta-analysis aimed to compare clinical outcomes between once-daily and twice-daily tacrolimus in de novo renal transplant patients. METHODS: Eligible studies were identified from the Cochrane Library Database, PubMed, and Embase until July 2022. Those randomized controlled trials (RCTs) evaluating once-daily versus twice-daily tacrolimus formulations in de novo renal transplantation were included. A summary risk ratio (RR) and standardized mean difference (SMD) with the 95% confidence interval (CI) were estimated using a random-effects model. RESULTS: In total, nine RCTs were included. There were no differences in biopsy-confirmed acute rejection rates between patients with once-daily and those with twice-daily tacrolimus (RR, 0.91; 95% CI, 0.73-1.13) in 12 months. Regarding renal function, there was no significant difference between the once-daily and twice-daily tacrolimus groups (SMD, -0.03; 95% CI, -0.12 to 0.07). In addition, the risk of graft failure, death, and adverse events in the first year was similar for the once-daily and twice-daily tacrolimus groups. CONCLUSION: Our major findings suggest that de novo renal transplantation recipients receiving once-daily tacrolimus immediately after transplantation have comparable efficacy and safety with those recipients who received twice-daily tacrolimus. Therefore, once-daily tacrolimus medication can be an alternative for de novo renal transplantation recipients.

The impact of Charlson Comorbidity Index on surgical complications and reoperations following simultaneous bilateral total knee arthroplasty.

Simultaneous bilateral total knee arthroplasty (TKA) might be associated with higher postoperative morbidity and mortality rates compared with staged bilateral TKA. However, risk factors for surgical complications and reoperations following simultaneous bilateral TKA remain elusive. We conducted this retrospective, single-surgeon case series from 2010 through 2019. A total of 1561 patients who underwent simultaneous bilateral TKA procedures were included. The outcome domains included 30-day and 90-day readmission events for medical or surgical complications and 1-year reoperation events. We performed logistic regression analysis and backward stepwise selection to identify possible risk factors, including age, sex, body mass index, diabetes mellitus (DM), rheumatoid arthritis, American Society of Anesthesiologist (ASA) classification, Charlson Comorbidity Index (CCI), receiving venous thromboembolism (VTE) prophylaxis, or blood transfusion. The overall 30-day, 90-day readmission, and 1-year reoperation rates were 2.11%, 2.88%, and 1.41%, respectively. Higher CCI score (CCI = 4+) was a risk factor for 90-day readmission (aOR: 2.783; 95% CI 0.621-12.465), 90 day readmission for surgical complications (aOR: 10.779; 95% CI 1.444-80.458), and 1 year reoperation (aOR: 4.890; 95% CI 0.846-28.260). Other risk factors included older age, higher ASA level, DM, and receiving VTE prophylaxis. In conclusion, high CCI scores were associated with increased risks of surgical complications and reoperations following simultaneous bilateral TKA procedures.

The safety and cost-analysis of simultaneous versus staged bilateral total knee arthroplasty in a Taiwan population.

BACKGROUND: In patients with advanced osteoarthritis (OA) of the bilateral knees, uncertainty remains as to whether simultaneous bilateral total knee arthroplasty (SiTKA) or staged TKA (StTKA) is the treatment of choice. The purpose of this study was to investigate the safety and relative cost of SiTKA vs StTKA in Taiwan patients. METHODS: Using the Big Data Center of Taipei Veterans General Hospital, we retrospectively reviewed all patients who underwent SiTKA or StTKA due to OA or spontaneous osteonecrosis of the knee from January 2011 to December 2016. We assessed length of stay, transfusion rate, early postoperative complications, 30- and 90-day readmission rate, 1-year reoperation rate, and the indication for reoperation. Furthermore, we analyzed the total cost of the two groups, including reimbursement from the national health insurance (NHI), cost of the procedures, and net income from each case. RESULTS: A total of 2016 patients (1565 SiTKA and 451 StTKA) were included in this study. The two groups had no significant differences in rates of complications, 30- and 90-day readmission, or 1-year reoperation. The length of stay was on average 5.0 days longer for StTKA ( p < 0.01). In terms of cost, all categories of medical costs were significantly lower for SiTKA, while the net hospital income was significantly higher for StTKA. CONCLUSION: SiTKA is a safe and cost-effective surgery. Both SiTKA and StTKA have similar rates of postoperative complications, readmission and reoperation, but SiTKA significantly reduces medical expenses for both the patient and the NHI.

Freezing nitrogen ethanol composite reduces periprosthetic infection caused by Staphylococcus aureus contaminated metal implants: An animal study.

BACKGROUND: Implant-associated infection remains a major complication of orthopedic surgery. The treatment of such infection is complicated by bacterial biofilm formation on the metal surfaces of implants. Biofilm surrounds and protects the bacteria against the organism's endogenous defense system and from external agents such as antibiotics and mechanical debridement. This study aims to evaluate whether freezing nitrogen ethanol composite (FNEC), the combination of liquid nitrogen and 95% ethanol in a 3 to 1 ratio, used frequently in bone tumor surgery, is capable of disinfecting Staphylococcus aureus contaminated implants. METHODS: The femurs of six New Zealand white rabbits were implanted with S. aureus-contaminated screws, half of which were treated with FNEC before implantation. The femurs were harvested 14 days after implantation. Histological analysis and TUNEL assay were conducted. The autoclaved screw, contaminated screw, and FNEC-treated contaminated screw were investigated using scanning electron microscopy to evaluate the biofilm structure. RESULTS: The FNEC-treated group had significantly lower relative C-reactive protein levels. An obvious periosteal reaction at the implant site was observed in all rabbits in the non-FNEC group but none was observed in the FNEC-treated group. The FNEC-treated group exhibited fewer empty lacunae, less inflammatory infiltration, and less bone necrosis. Immunohistochemical analysis showed no S. aureus in bone tissue from the FNEC-treated group. Scanning electron microscopy showed disruption of the biofilm on the contaminated screw treated with FNEC. CONCLUSION: FNEC showed potential in disinfecting S.aureus-contaminated implants. Further investigation is warranted, such as the effect on the implant-cement-bone interface, for FNEC to be used clinically in treating implant-associated infection.

Does the Addition of iPACK Block to Adductor Canal Block Provide Improved Analgesic Effect in Total Knee Arthroplasty? A Systematic Review and Meta-Analysis.

The interspace between popliteal artery and the capsule of posterior knee (iPACK) block was proposed in recent years to relieve posterior knee pain. Since adductor canal block (ACB) and iPACK involve different branches of the sensory nerves, it is theoretically feasible to combine iPACK block and ACB to relief pain after total knee arthroplasty (TKA). We aim to validate the efficacy of adding iPACK block to ACB in the setting of a multimodal pain management protocol following TKA. A comprehensive literature review on Web of Science, Embase, the Cochrane Library, and PubMed was performed. Eight studies (N = 1,056) that compared the efficacy of iPACK block + ACB with ACB alone were included. Primary outcomes consisted of Visual Analogue Scale (VAS) score at rest or during activity at various time points. Secondary outcomes include opioids consumption, walking distance, and length of hospital stay (LOS). Compared to ACB alone, VAS scores at rest (standardized mean difference [SMD]: -1.18; 95% confidence interval [CI]: -2.05 to -0.30) and during activity (SMD: -0.26; 95% CI: -0.49 to -0.03) on the day of surgery were lower in the iPACK block + ACB group. However, the difference did not reach the minimal clinically important difference. Opioids consumption at postoperative 24 hours was lower in the iPACK + ACB group (SMD: -0.295; 95% CI: -0.543 to -0.048). VAS score on postoperative day (POD) 1 and POD2, opioids consumption from 24 to 48 hours, walking distance, and LOS were not different. In conclusion, the addition of iPACK block to ACB in a multimodal pain management protocol can effectively reduce opioids consumption in the early postoperative period. This is a level III, meta-analysis study.

IL-1b in the Secretomes of MSCs Seeded on Human Decellularized Allogeneic Bone Promotes Angiogenesis.

Angiogenesis plays an important role in the development of bone and bone regeneration to provide the required molecules. Mesenchymal stem cells (MSCs) are pluripotent, self-renewing, and spindle-shaped cells, which can differentiate into multiple lineages such as chondrocytes, osteocytes, and adipocytes. MSCs derived from bone marrow (BMMSCs), adipose tissue (ADMSCs), and Wharton's jelly (UCMSCs) are popular in the field of tissue regeneration. MSCs have been proposed that can promote bone regeneration by enhancing vascularization. In this study, the angiogenic potential of secretomes of undifferentiated and osteo-differentiated BMMSCs, ADMSCs, and UCMSCs seeded on human decellularized allogeneic bone were compared. Human umbilical vein endothelial cells (HUVECs) were treated with MSC secretomes. Cell growth, cell migration, and angiogenesis of HUVECs were analyzed by MTT, wound healing, and tube formation assays. Angiogenic gene expression levels of MSCs were evaluated using real-time quantitative PCR. Antibody neutralization was performed to validate the candidate target. Our study demonstrates that the angiogenic gene expression profile is tissue-dependent and the angiogenic ability of secretomes is independent of the state of differentiation. We also explore that IL-1b is important for MSC angiogenic potential. Taken together, this study proves that IL-1b in the secretomes plays a vital role in angiogenesis.

Cementless primary or revision stem in revision hip arthroplasty for aseptic stem loosening with Paprosky type I/II femoral defect?

BACKGROUND: The use of primary or revision stem during revision total hip arthroplasty (THA) for aseptic stem loosening with Paprosky type I/II femoral defect remains controversial. The aim of this study was to compare the outcomes of patients who underwent revision THA with a primary or revision stem. METHODS: We retrospectively reviewed 78 patients who received revision THA for aseptic stem loosening using primary (N = 28) or revision stems (N = 50). The bone defects were classified as Paprosky type I or II. The mean follow-up duration was 72.3 ± 34.7 months. The primary outcome domains included surgical complications and implant failures. The secondary outcome domains included medical complications, 30- and 90-day readmission, and Harris hip score (HHS). RESULTS: The use of revision stem was associated with a higher incidence than primary stem of patient complications (60.0% vs. 32.1%, p = 0.018), including intraoperative femur fracture (28.0% vs. 7.1%, p = 0.029) and greater trochanter fracture (16.0% vs. 0%, p = 0.045). The implant survival rate was comparable between groups. HHS at the final follow-up was similar. CONCLUSION: With a lower risk of surgical complications and a similar rate of mid-term implant survival, cementless primary stem appears superior to revision stem in revision THA for aseptic stem loosening with Paprosky type I/II femoral defect.

A Cryoprotectant-Gel Composite Designed to Preserve Articular Cartilage during Frozen Osteoarticular Autograft Reconstruction for Malignant Bone Tumors: An Animal-Based Study.

OBJECTIVE: We designed a highly adhesive cryoprotectant-gel composite (CGC), based on regular liquid-form cryoprotectant base (CB), aiming to protect cartilage tissue during frozen osteoarticular autograft reconstruction for high-grade sarcoma around the joint. This study aimed to evaluate its effectiveness in rat and porcine distal femur models. DESIGN: Fresh articular cartilage samples harvested from distal rat and porcine femurs were divided into 4 test groups: untreated control group, liquid nitrogen (LN) freezing group, LN freezing group pretreated with CB (CB group), and LN freezing group pretreated with CGC (CGC group). Microscopic and macroscopic evaluation of cartilage condition, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, and apoptotic protein analysis of chondrocytes were performed to confirm our results. RESULTS: In the rat model, CGC could prevent articular cartilage from roughness and preserve more proteoglycans when compared with the LN freezing and CB groups. Western blot analysis showed CGC could prevent cartilage from LN-induced apoptosis supported by caspase-3/8 apoptotic signaling cascade. Macroscopically, we observed CGC could reduce both articular clefting and loss of articular luminance after freezing in the porcine model. In both models, CGC could reduce articular chondrocytes from degeneration. Fewer TUNEL-positive apoptotic and more viable chondrocytes in cartilage tissue were observed in the CGC group in our animal models. CONCLUSION: Our study proved that CGC could effectively prevent cartilage surface and chondrocytes from cryoinjury after LN freezing. Freezing articular cartilage surrounded with high concentration of CGC can be a better alternative to preserve articular cartilage during limb salvage surgery for malignant bone tumor.

Analyzing BMP2, FGFR, and TGF Beta Expressions in High-Grade Osteosarcoma Untreated and Treated Autografts Using Proteomic Analysis.

In the last few decades, biological reconstruction techniques have improved greatly for treating high-grade osteosarcoma patients. To conserve the limb, and its function the affected tumor-bearing bones have been treated using liquid nitrogen and irradiation processes that enable the removal of entire tumors from the bone, and these treated autografts can be reconstructed for the patients. Here, we focus on the expressions of the growth factor family proteins from the untreated and treated autografts that play a crucial role in bone union, remodeling, and regeneration. In this proteomic study, we identify several important cytoskeletal, transcriptional, and growth factor family proteins that showed substantially low levels in untreated autografts. Interestingly, these protein expressions were elevated after treating the tumor-bearing bones using liquid nitrogen and irradiation. Therefore, from our preliminary findings, we chose to determine the expressions of BMP2, TGF-Beta, and FGFR proteins by the target proteomics approach. Using a newly recruited validation set, we successfully validate the expressions of the selected proteins. Furthermore, the increased growth factor protein expression after treatment with liquid nitrogen may contribute to bone regeneration healing, assist in faster recovery, and reduce local recurrence and metastatic spread in high-grade sarcoma patients.

The effective distance and cooling rate of liquid nitrogen-based adjunctive cryotherapy for bone tumors ex vivo.

BACKGROUND: Liquid nitrogen (LN) has been used as an adjuvant cryotherapy for bone tumors including giant-cell tumor of the bone (GCTB) to remove residual tumor cells after curettage. This study evaluated variables related to the efficacy of LN-based cryoablation in the context of adjuvant treatment of GCTB using porcine femur bone model. METHODS: A porcine femur bone model was adopted to simulate intralesional cryotherapy. A LN-holding cavity (point 1, nadir) in the medial epicondyle, 4 holes (points 2-5) in the shaft situated 5, 10, 15, and 20 mm away from the proximal edge of the cavity, and 2 more holes (points 6 and 7) in the condyle cartilage (10 and 20 mm away from the distal edge of the cavity) were made. The cooling rate was compared between the 5 points. The cellular morphological changes and DNA damage in the GCTB tissue attributable to LN-based cryotherapy were determined by H&E stain and TUNEL assay. Cartilage tissue at points 6 and 7 was examined for the extent of tissue injury after cryotherapy. RESULTS: The temperature kinetics at points 1, 2 reached the reference target and were found to be significantly better than the reference (both p < 0.05). The target temperature kinetics were not achieved at points 4 and 5, which showed a significantly lower cooling rate than the reference (both p < 0.001) without reaching the -60°C target. Compared with untreated samples, significantly higher proportion of shrunken or apoptotic cells were found at points 1-3; very small proportion were observed at points 4, 5. Significantly increased chondrocyte degeneration was observed at point 6, and was absent at point 7. CONCLUSION: The cryotherapy effective range was within 5 mm from nadir. Complications were restricted to within this distance. The cooling rate was unchanged after three repeated cycles of cryotherapy.