Undergoing Hip Replacement Surgery Research Articles

Serum miRNA-142 and BMP-2 are markers of recovery following hip replacement surgery for femoral neck fracture.

The present study aimed to investigate the changes in miRNA-142 and bone morphogenetic protein-2 (BMP-2) expression before and after hip replacement surgery, and to determine their association with receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). For this purpose, 142 cases of hip arthroplasty in patients with femoral neck fracture were selected as the research group, and 50 cases of healthy individuals who underwent a physical examination during the same time period were selected the control group. Serum miR-142 and BMP-2 levels were measured by RT-qPCR before and after surgery in the research group and the control group. Serum RANKL and OPG levels were detected before and after surgery by enzyme-linked immunosorbent assay (ELISA). The levels of serum miR-142 and BMP-2 in the research group were significantly lower than those in the control group. At 1 month after surgery, the levels of serum miR-142 and BMP-2 in the research group were significantly higher than those before surgery, and at 6 months after surgery, and they were higher than those in the control group. Pearson's correlation analysis revealed that the serum levels of miR-142 positively correlated with the BMP-2 levels before surgery, at 1 month after surgery, and at 6 months after surgery in the research group. The results of ROC curve analysis revealed that the AUC values of serum miR-142 and BMP-2 were 0.911 and 0.861, respectively. At 1 month after surgery, the levels of serum miR-142 and BMP-2 in group A (patients with a good or excellent recovery) were significantly higher than those in group B (patients with a fair or poor recovery). The levels of serum RANKL and OPG in the research group significantly increased at 1 month after surgery. The serum levels of miR-142 and BMP-2 positively correlated with those of RANKL and OPG before surgery and at 1 month after surgery. On the whole, the findings of the present study indicate that pre-operative serum miR-142 and BMP-2 levels are valuable for evaluating the post-operative recovery of patients with femoral neck fracture undergoing hip replacement surgery. In addition, in the present study, at 1 month after surgery, the levels of both miR-142 and BMP-2 were related to the recovery of the patients, and positively correlated with the RANKL and OPG levels.

Sclerostin Regulation, Microarchitecture, and Advanced Glycation End-Products in the Bone of Elderly Women With Type 2 Diabetes.

Increased circulating sclerostin and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Whether the expression of the sclerostin-encoding SOST gene is altered in T2D, and whether it is associated with AGEs accumulation or regulation of other bone formation-related genes is unknown. We hypothesized that AGEs accumulate and SOST gene expression is upregulated in bones from subjects with T2D, leading to downregulation of bone forming genes (RUNX2 and osteocalcin) and impaired bone microarchitecture and strength. We obtained bone tissue from femoral heads of 19 T2D postmenopausal women (mean glycated hemoglobin [HbA1c] 6.5%) and 73 age- and BMI-comparable nondiabetic women undergoing hip replacement surgery. Despite similar bone mineral density (BMD) and biomechanical properties, we found a significantly higher SOST (p = .006) and a parallel lower RUNX2 (p = .025) expression in T2D compared with non-diabetic subjects. Osteocalcin gene expression did not differ between T2D and non-diabetic subjects, as well as circulating osteocalcin and sclerostin levels. We found a 1.5-fold increase in total bone AGEs content in T2D compared with non-diabetic women (364.8 ± 78.2 versus 209.9 ± 34.4 μg quinine/g collagen, respectively; p < .001). AGEs bone content correlated with worse bone microarchitecture, including lower volumetric BMD (r = -0.633; p = .02), BV/TV (r = -0.59; p = .033) and increased trabecular separation/spacing (r = 0.624; p = .023). In conclusion, our data show that even in patients with good glycemic control, T2D affects the expression of genes controlling bone formation (SOST and RUNX2). We also found that accumulation of AGEs is associated with impaired bone microarchitecture. We provide novel insights that may help understand the mechanisms underlying bone fragility in T2D. © 2020 American Society for Bone and Mineral Research (ASBMR).

Effects of edaravone on postoperative cognitive function in elderly patients undergoing hip joint replacement surgery: A randomized controlled trial.

Postoperative cognitive dysfunction (POCD) is a complication of central nervous system in patients after surgery. Edaravone as a brain-protective agent may have protective effect on postoperative cognitive function. The study was designed to explore the effects of edaravone on postoperative cognitive function in elderly patients undergoing hip joint replacement surgery and potential mechanism. Patients undergoing hip joint replacement surgery were randomly allocated into 2 groups: the edaravone group (group E) and the control group (group C). Group E received intravenous edaravone at a dose of 0.5mg/kg after induction of anesthesia, while group C received normal saline. The cognitive function was evaluated with the Mini-Mental State Examination (MMSE) 1day before surgery,3 days and the 7 days after surgery. Patients' plasma samples were collected to detect the levels of S100β protein (S100β), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), superoxide dismutase (SOD) and malondialdehyde (MDA) before the induction of anesthesia, at the end of surgery and on postoperative day 3. The MMSE scores in group E were higher than those of group C 3 days after surgery (25.98±1.99 vs 24.86±1.86, p=0.003). There were remarkable rises (p<0.05) in plasma IL-6, S100βand MMP-9 levels at the end of surgery and on postoperative day 3 in the two groups, however, edaravone pretreatment could reduce these levels to a certain extent compared with group C (p<0.05).In group E, the SOD concentration was higher at the end of surgery (16.03±2.46U/ml vs. 13.65±2.53U/ml, p=0.0001), while the MDA level was lower on postoperative day 3 than those in group C (7.01±2.37nmol/ml vs. 11.34±3.18nmol/ml, p=0.0001). The results indicated that preoperative intervention with edaravone may improve the postoperative cognitive function in elderly patients undergoing hip joint replacement surgery.

CD4+FOXP3+ T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired.

There is evolving evidence that dysregulation of immune homeostasis in the bone marrow (BM) adjacent to the inflamed joints is involved in the pathogenesis of. In this study, we are addressing the phenotype and function of regulatory T cells (Tregs) residing in the BM of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). BM and peripheral blood samples were obtained from RA and OA patients undergoing hip replacement surgery. The number and phenotype of Tregs were analyzed by flow cytometry and immunohistochemistry. The function of Tregs was investigated ex vivo, addressing their suppressive activity on effector T cells. [3H]-Thymidine incorporation assay and specific enzyme-linked immunosorbent assay were used for quantification of cell proliferation and pro-inflammatory (TNF, IFN-γ) cytokine release, respectively. Significantly lower numbers of CD4+FOXP3+ T cells were found in the BM of patients with RA compared to control patients with OA. High expression of CD127 (IL-7α receptor) and relatively low expression of CXCR4 (receptor for stromal cell-derived factor CXCL12) are characteristics of the CD4+FOXP3+ cells residing in the BM of RA patients. The BM-resident Tregs of RA patients demonstrated a limited suppressive activity on the investigated immune response. Our results indicate that the reduced number and impaired functional properties of CD4+FOXP3+ T cells present in the BM of RA patients may favor the inflammatory process, which is observed in RA BM.

The Effect of Body Mass Index on the Functional Outcome of Patients with Hip Replacement

Objective: The objective of this study is to investigate the association between body mass index (BMI) and the functional progress among patients with a recent hip replacement. Data suggest that a number of medical societies and organizations are restricting patient access to joint replacement surgeries based on the patient's BMI. This restriction seems to be related to the increased risk of complications, primarily wound infections, at the time of surgery. Few studies have been conducted on the relationship between BMI and outcomes during rehabilitation after hip replacement surgery. Design: Retrospective cohort study. Setting: All patients admitted to a rehabilitation hospital, with a recent diagnosis of hip replacement and available hospital admission height and weight data during the years 2014-2017. Main Outcome Measure: Functional independence measure (FIM) gain per day of patients by BMI category. Results: The chart review identified 479 patients had undergone hip replacement surgery. Over half of the patients were overweight or obese. FIM efficiency (FIM change/day) was the highest in the obese class II category (3.65), followed by obese class III (3.60). The differences in FIM efficiency between the normal and obese I groups reached statistical significance in favor of obese I (P = 0.024). Conclusion: This study did not demonstrate that obesity significantly impairs functional outcomes during the rehabilitation process after hip replacement surgery.

Evaluation and role of prealbumin levels on postoperative stay in orthopaedic surgical patients

In this present research study we tried to evaluate whether serum Prealbumin levels would serve as a prognosticator of length of stay in hospital for elderly orthopaedic patients who have underwent hip replacement surgery. Our study consisted of a set of 54 patients admitted to a Malla Reddy Institute of Medical Sciences in the year 2014. After initial examinations all the patients were categorised with decreased Prealbumin levels, normal Prealbumin levels, or increased prealbumin levels were monitored during their stay in hospital. The physical parameters data was collected that includes: patients age, length of stay, blood glucose, hemoglobin, RBC, WBC, Prealbumin, and post-operative diet intake. The experimental data was analyzed using SPSS software and probabilities approaching p< 0.10 were considered and levels of p< 0.05 were deemed to be significant. Our research study shows a substantial and significant relationship between Prealbumin levels at admission and length of patient stay during post-operative recovery.

Potential Opioid-Related Adverse Drug Events Are Associated With Decreased Revenue in Hip Replacement Surgery in the Older Population.

Introduction:Opioid-related adverse drug events (ORADEs) are an increasingly recognized complication associated with the common prescription of opioids after orthopedic surgery. In this study, we attempted to understand how potential ORADEs following hip replacement surgery in older patients affected hospital length of stay, hospital revenue, and their association with specific risk factors and clinically relevant diseases occurring during hospitalization.Methods:We conducted a retrospective study using the Centers for Medicare and Medicaid Services Administrative Database to analyze Medicare discharges after hip replacement surgery to identify potential ORADEs. The impact of potential ORADEs on mean hospital length of stay (LOS) and hospital revenue was analyzed.Results:The potential ORADE rate in patients who underwent hip replacement surgery was 8.6%. The mean LOS for discharges with a potential ORADE was 1.41 days longer than that for discharges without an ORADE. The mean hospital revenue per day with a potential ORADE was US$1708 less than without an ORADE. Potential ORADEs were also found to be strongly associated with poor patient outcomes such as pneumonia, septicemia, and shock.Discussion:Potential ORADEs in hip replacement surgery in older patients are associated with longer hospitalizations, decreased hospital revenue per day, certain patient risk factors, and clinically relevant diseases occurring during hospitalizations. Our finding of an association between potential ORADEs and decreased hospital revenue per day may be attributed to the management of these adverse events, as a patient may need to undergo additional testing, may need additional treatment regimens, and may need a higher level of care.Conclusion:By reducing the use of opioids and employing a multimodal analgesic approach, we may improve patient care, decrease hospital lengths of stay, and increase hospital revenue

The Impact Of Decision Aids On Adults Considering Hip Or Knee Surgery.

Trials of decision aids developed for use in shared decision making find that patients engaged in that process tend to choose more conservative treatment for preference-sensitive conditions. Shared decision making is a collaborative process in which clinicians and patients discuss trade-offs and benefits of specific treatment options in light of patients' values and preferences. Decision aids are paper, video, or web-based tools intended to help patients match personal preferences with available treatment options. We analyzed data for 2012-15 about patients within the ten High Value Healthcare Collaborative member systems who were exposed to condition-specific decision aids in the context of consultations for hip and knee osteoarthritis, with the intention that the aids be used to support shared decision making. Compared to matched patients not exposed to the decision aids, those exposed had two-and-a-half times the odds of undergoing hip replacement surgery and nearly twice the odds of undergoing knee replacement surgery within six months of the consultation. These findings suggest that health care systems adopting decision aids developed for use in shared decision making, and used in conjunction with hip and knee osteoarthritis consultations, should not expect reduced surgical utilization.

Development of clinically relevant in vivo metastasis models using human bone discs and breast cancer patient-derived xenografts

BackgroundLate-stage breast cancer preferentially metastasises to bone; despite advances in targeted therapies, this condition remains incurable. The lack of clinically relevant models for studying breast cancer metastasis to a human bone microenvironment has stunted the development of effective treatments for this condition. To address this problem, we have developed humanised mouse models in which breast cancer patient-derived xenografts (PDXs) metastasise to human bone implants with low variability and high frequency.MethodsTo model the human bone environment, bone discs from femoral heads of patients undergoing hip replacement surgery were implanted subcutaneously into NOD/SCID mice. For metastasis studies, 7 patient-derived xenograft tumours (PDX: BB3RC32, ER+ PR+ HER2−; BB2RC08, ER+ PR+ ER2−; BB6RC37, ER− PR− HER2− and BB6RC39, ER+ PR+ HER2+), MDA-MB-231-luc2, T47D-luc2 or MCF7-Luc2 cells were injected into the 4th mammary ducts and metastases monitored by luciferase imaging and confirmed on histological sections. Bone integrity, viability and vascularisation were assessed by uCT, calcein uptake and histomorphometry. Expression profiling of genes/proteins during different stages of metastasis were assessed by whole genome Affymetrix array, real-time PCR and immunohistochemistry. Importance of IL-1 was confirmed following anakinra treatment.ResultsImplantation of femoral bone provided a metabolically active, human-specific site for tumour cells to metastasise to. After 4 weeks, bone implants were re-vascularised and demonstrated active bone remodelling (as evidenced by the presence of osteoclasts, osteoblasts and calcein uptake). Restricting bone implants to the use of subchondral bone and introduction of cancer cells via intraductal injection maximised metastasis to human bone implants. MDA-MB-231 cells specifically metastasised to human bone (70% metastases) whereas T47D, MCF7, BB3RC32, BB2RC08, and BB6RC37 cells metastasised to both human bone and mouse bones. Importantly, human bone was the preferred metastatic site especially from ER+ PDX (100% metastasis human bone compared with 20–75% to mouse bone), whereas ER-ve PDX developed metastases in 20% of human and 20% of mouse bone. Breast cancer cells underwent a series of molecular changes as they progressed from primary tumours to bone metastasis including altered expression of IL-1B, IL-1R1, S100A4, CTSK, SPP1 and RANK. Inhibiting IL-1B signalling significantly reduced bone metastasis.ConclusionsOur reliable and clinically relevant humanised mouse models provide significant advancements in modelling of breast cancer bone metastasis.

Outcomes of Combined Neck and Trochanter Fractures of the Femur Treated with Cephallomedullary Nail in Elderly.

PurposeProximal femur fractures are classified into intracapsular neck fractures and extracapsular trochanteric fractures, and several related treatment recommendations in elderly patients have already been introduced. Importantly, we have observed cases of combined intra and extracapsular fractures (i.e., ipsilateral neck and trochanter fractures). The purpose of this study is to report the outcomes of combined neck and trochanter fractures of the femur treated with cephalomedullary nail (CMN) in elderly patients.Materials and MethodsFrom January 2010 to December 2014, 410 patients with proximal femoral fractures were fixed using CMN; among this group, 37 patients with combined neck and trochanter fractures were identified. Two of these patients died fewer than three months after injury and another two did not return for follow-up. Thirty-three patients were included and reviewed retrospectively in this study.ResultsAll patients were injured by simple fall. Bone union was obtained in 28 of 33 patients. Of the five patients who failed treatment, three experienced implant penetration through head (cut-through and cut-out), one had breakage of CMN and the last one had a loosening of internal fixation device with persistent non-union at final follow-up. The former four patients underwent hip replacement surgery and the latter refused surgery because he had low demand in daily life and many medical problems.ConclusionEighty-five percent of elderly patients with combined neck and trochanter fractures of the femur treated with CMN achieved bone union; these complex fractures require more accurate reduction than usual extra-articular intertrochanteric fractures.

Association of global DNA hypomethylation with post-operative cognitive dysfunction in elderly patients undergoing hip surgery.

Post-operative cognitive dysfunction (POCD) is a decline of cognitive status that commonly occurs after surgery in elderly patients. Whether DNA methylation is associated with the development of POCD remains unclear. Subjects (N=124) older than 65years-of-age undergoing hip replacement surgery were enrolled. A battery of neuropsychiatric tests was used to examine the perioperative cognitive function of the patients. Early POCD was analyzed using the reliable change index (RCI), and subjects were diagnosed with POCD if RCI<-1.96. Peripheral leukocyte DNA was isolated, and DNA methylation was measured via 5-methylcytosine (mC) using Elisa. Twenty-four patients (19.4%) developed early POCD. There was no difference in baseline 5-mC levels by POCD status. The 5-mC levels significantly decreased on day 7 after surgery in patients who developed early POCD (P=.004), but did not change in non-POCD patients. Moreover, post-operative 5-mC levels were significantly lower in POCD patients than those in non-POCD patients (P=.003). Bivariate logistic models adjusted for age, gender, BMI, duration of anesthesia, and education level clearly demonstrated an independent association between post-operative 5-mC level and early POCD. Post-operative global hypomethylation of leukocyte DNA was associated with the development of early POCD. ClinicalTrial, NCT02965235. Registered 16 November 2016, https://www.clinicaltrials.gov/ct2/results?term=NCT02965235&rank=1#rowId0.

Rôle de la voie d’abord dans la satisfaction du patient après arthroplastie totale de hanche

BackgroudAt present, the posterolateral, the direct lateral and direct anterior approach (DAA) are the most frequently used techniques for total hip arthroplasty (THA), however there is no clear superiority of one of the approaches based on clinical outcome measures. The goal of this study is to lead the patient and the surgeon to an optimal treatment by providing them with relevant information based on patient reported outcome measures (PROMs). MethodsPatient satisfaction and hip function one year postoperatively were investigated retrospectively in a cohort of patients who underwent hip replacement surgery by DAA on one hip and by posterolateral or direct lateral approach on the contralateral hip. Additionally, a control group who underwent the DAA bilaterally was used for comparison. ResultsNo difference in hip function was found between the DAA and the posterolateral or direct lateral approach, measured with the Hip disability and Osteoarthritis Outcome Score (HOOS) questionnaire at least one year postoperatively to the last THA in the study group. Also in the control group no difference was found between the hips. However, the overall scores of the control group were higher, although not statistically significant, than those of the study group (p=0.055). And a majority of the study group preferred the DAA (68%), with the reasons reported being faster recovery, less sleeping disturbance and earlier mobilization. ConclusionAs expected, the postoperative hip function is similar, but patients’ preference is not. The latter result might be true or possibly influenced by preoperative psychological factors and mental health. The DAA and the posterolateral or direct lateral approaches have shown to lead to a similar hip function, but a majority of patients subjectively prefer the DAA. Level of evidenceIII

Patient satisfaction in different approaches for total hip arthroplasty

BackgroundAt present, the posterolateral, the direct lateral and direct anterior approach (DAA) are the most frequently used techniques for total hip arthroplasty (THA), however there is no clear superiority of one of the approaches based on clinical outcome measures. The goal of this study is to lead the patient and the surgeon to an optimal treatment by providing them with relevant information based on patient reported outcome measures (PROMs). MethodsPatient satisfaction and hip function one year postoperatively were investigated retrospectively in a cohort of patients who underwent hip replacement surgery by DAA on one hip and by posterolateral or direct lateral approach on the contralateral hip. Additionally, a control group who underwent the DAA bilaterally was used for comparison. ResultsNo difference in hip function was found between the DAA and the posterolateral or direct lateral approach, measured with the Hip disability and Osteoarthritis Outcome Score (HOOS) questionnaire at least one year postoperatively to the last THA in the study group. Also in the control group no difference was found between the hips. However, the overall scores of the control group were higher, although not statistically significant, than those of the study group (p=0.055). And a majority of the study group preferred the DAA (68%), with the reasons reported being faster recovery, less sleeping disturbance and earlier mobilization. ConclusionAs expected, the postoperative hip function is similar, but patients’ preference is not. The latter result might be true or possibly influenced by preoperative psychological factors and mental health. The DAA and the posterolateral or direct lateral approaches have shown to lead to a similar hip function, but a majority of patients subjectively prefer the DAA. Level of evidenceIII.

The effect of spinal anesthetic technique on neutrophil to lymphocyte ratio and postoperative mortality in elderly patients with coronary artery disease undergoing hip replacement surgery

The effect of spinal anesthetic technique on neutrophil to lymphocyte ratio and postoperative mortality in elderly patients with coronary artery disease undergoing hip replacement surgery

The changes in systemic monocytes in humans undergoing surgical decompression for degenerative cervical myelopathy may influence clinical neurological recovery

BackgroundDegenerative cervical myelopathy (DCM) is the most common cause of non-traumatic spinal cord injury worldwide. Surgical decompression is recommended as the preferred treatment strategy for DCM as it halts disease progression and improves neurologic symptoms. We previously demonstrated that neuroinflammation, including monocytes, plays a critical role in the pathobiology of DCM and in ischemic-reperfusion injury (IRI) following surgical decompression. Monocytes are able to enter the spinal cord and brain tissues due to damage to the blood spinal cord and blood brain barrier following injury. Studies have demonstrated that stroke patients and individuals undergoing hip replacement surgery have increased systemic levels of monocytes. Additionally, changes in the signalling responses of monocytes are associated with post-surgical recovery or with ischemic neural tissue damage. Herein, we investigated the role of systemic monocytes as a predictive biomarker for clinical recovery following decompressive surgery for DCM. FindingsThere was a 2-fold increase in the number of monocytes in DCM patients at 24 h following decompression as compared to baseline levels, which was associated with a significant improvement in the modified Japanese Orthopedic Association scale (mJOA) at 6-months after surgery (p < .0001). In a mouse model of DCM, depleting acute monocytes reduced the non-classical (Ly6Clow) subset from circulation (p < .05) and resulted in a 1.8-fold increase in CD11b expression in the spinal cord at 5 weeks following decompression. Acute monocyte depletion was accompanied by a modest decline in long-term overground locomotion, as evidenced by significantly reduced hindlimb swing speed. ConclusionsThis work demonstrated that decompressive surgery leads to an acute increase in peripheral monocytes in human DCM patients, which is modestly associated with clinical recovery. We anticipate that this work could contribute to the implementation of routine measurements of blood monocyte subsets, their activation state, and production of cytokines following decompressive surgery. This information could help to select perioperative anti-inflammatory treatments that can enhance the beneficial effects of decompressive surgery and reduce the incidence of post-operative complications, while avoiding a reduction in systemic monocytes.

The clinical application of ultra-sound guided anterior lumbar plexus combined with buttock epithelial nerve block on elderly patients undergoing hip replacement surgery

Objective To observe the clinical application of ultra-sound guided anterior lumbar plexus combined with buttock epithelial nerve block on elderly patients undergoing hip replacement surgery. Methods Sixty elderly patients (range from 60 to 80 years old) scheduled for unilateral hip replacement surgery were randomly divided to anterior lumbar plexus combined with buttock epithelial nerve block group (group A) and anterior lumbar plexus nerve block group (group B) by random number table method. The airways of all the patients were controlled by laryngeal mask airway (LMA) in both groups. The bispectral index (BIS) of patients in both groups was maintained in the range of 45-55. The heart rate, systolic and diastolic blood pressure when cutting were recorded respectively. The dosage of sulfentanyl, Visual Analogue Scale (VAS) score at 1, 6, 12 h and 24 h after surgery were recorded. The period from end of surgery to extubation, first off-bed activity after surgery were evaluated. Results The heart rate and blood pressure of patients in group A were less than those indexes of patients in group B at T1, T2, T3 (P<0.05). The averaged dosage using of sulfentanyl of group A was less than the dosage of group B (P<0.05). The periods from end of surgery to extubation and off-bed activity of group A were shorter than the periods in group B (P<0.05). The VAS scores at 1, 6, 12 h after surgery in group A were lower than those scores in group B (P<0.05). Conclusions Compared with anterior lumbar plexus nerve block, ultra-sound guided anterior lumbar plexus combined with buttock epithelial nerve block could help maintain circulation stability, reduce usage of opioids during operation, shorten the period of off-bed activity and the period from end of surgery to extubation and offer better analgesia effect on elderly patients undergoing hip replacement surgery. Key words: Buttock epithelial nerve block; Ultra-sound guidance; Anterior lumbar plexus nerve block; Rip replacement surgery; Aged

PF161 THIOREDOXIN SYSTEM INHIBITORS ARE EFFECTIVE AGAINST B CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN VITRO AND IN VIVO

Background:B‐cell acute lymphoblastic leukemia (B‐ALL) is a heterogeneous hematological disorder characterized by accumulation of B cell precursors. Although undeniable improvement has been made in the therapy ofB‐ALL (&gt;90% of pediatric patients experience remission), there are still specific subtypes associated with poor outcome. Among such subtypes are B‐ALL with mixed lineage leukemia rearrangements (MLLr ALL) or BCR‐ABL1 fusion protein (BCR‐ABL1+ ALL). Importantly, MLLr ALL does not respond to novel immunotherapies, thus novel treatment options are urgently needed. More and more data highlight disturbed redox homeostasis as a novel target in cancer treatment. Cancer cells upregulate different antioxidant machineries to overcome excessive production of reactive oxygen species (ROS) in result of increased metabolism and uncontrolled proliferation. One of such ROS‐defending systems is the thioredoxin (TXN) system, which is composed of three independent enzymes: thioredoxin reductase (TXNRD), thioredoxin (TXN), and peroxiredoxin (PRDX).Aims:To investigate the efficacy of TXN‐family enzymes inhibitors – auranofin (AUR) and adenanthin (ADE) in B‐ALL in vitro and in vivo.Methods:Primary material was isolated from pediatric and adult B‐ALL patients at diagnosis. Primograft B‐ALL samples representing BRC‐ABL1+ and MLLr ALL were generated in NOD scid gamma (NSG) mice by tail vein injections of primary B‐ALL cells. The engraftment of leukemic cells was assessed by whole blood staining and flow cytometry. Primary bone marrow derived mesenchymal stem cells (BM‐MSC) were isolated from non‐leukemic donors who underwent hip replacement surgery. Cytostatic/cytotoxic effects of TXN‐family enzymes inhibitors, AUR and ADE were assessed in mono‐ and co‐culture with BM‐MSC by MTT viability assay or by trypan blue exclusion method. The efficacy of AUR in vivo was evaluated in MLLr ALL patient derived xenograft model in NSG mice. For mechanistic studies we used SEM cell line representing MLLr ALL.Results:We have previously found increased mRNA and protein levels of particular enzymes of TXN system in B‐ALL cell lines and primary cells, thus we evaluated efficacy of two thioredoxin system inhibitors, AUR and ADE in B‐ALL primary cells. We found that both inhibitors decreased the viability of various B‐ALL cells grown not only in monoculture, but also in a co‐culture with bone marrow derived mesenchymal stem cells (BM‐MSC) of confirmed characteristics (Fig. 1A), which were shown to protect leukemic cells from drugs toxic effects. Next, we compared the effects of both inhibitors against normal peripheral blood mononuclear cells (PBMC) and found that ADE is significantly more toxic than AUR, thus we chose the latter for further studies. Accordingly, we observed that in patient derived xenograft model of MLLr ALL, AUR delayed the progression and prolonged the survival of NSG mice (Fig. 1B). Elucidating the mechanism standing behind AUR toxic effects, we found increased oxidative stress, as we observed elevated ROS levels which were abrogated by ROS scavengers, pyruvate and catalase. In addition, we observed that AUR induced oxidative stress biomarker, heme oxygenase 1 and moderate DNA oxidative damage in primograft B‐ALL cells (Fig. 1C).Summary/Conclusion:Above results show that targeting TXN system with their inhibitors can be considered as novel approach in the treatment of B‐ALL. Considering that AUR is an FDA approved drug, it could be repurposed and tested in combination with other targeted drugs in B‐ALL.image

Effects of stellate ganglion block on attention and executive function in middle-aged and elderly patients after surgery

Objective To investigate the effects of stellate ganglion block(SGB)on attention and executive function in middle-aged and elderly patients after surgery. Methods Middle-aged and elderly patients aged 55-75 years who underwent hip replacement surgery under lumbar anesthesia were randomized into a control group and an SGB group.Patients in the SGB group received ultrasound-guided stellate ganglion block 30 min before surgery, and patients in the control group were given no additional treatment before surgery.All patients were tested with a modified version of the Trail Making Test-Part A(TMT-A)and a modified version of the Symbol Digit Modalities Test(SDMT)1 day before surgery and 7 days after surgery.The Z-score method was used to diagnose postoperative attention and/or executive function impairment. Results The modified versions of TMT-A and SDMT had good reliability and validity among Chinese middle-aged and elderly people aged 55-75 years.Age was the main influencing factor for the two tests, and their two parallel versions had good alternate-form reliability.There was no significant difference between the control group and the SGB group in scores of modified TMT-A and SDMT at 7 days after surgery(P>0.1). However, the incidence of attention and/or executive function impairment was lower in the SGB group than in the control group(19.3% vs.36.6%, P<0.05). Conclusions The modified TMT-A and SDMT have good reliability and validity among Chinese middle-aged and elderly people aged 55-75 years.Preoperative SGB may protect attention and executive function in middle-aged and elderly patients. Key words: Stellate ganglion; Arthroplasty, replacement, hip; Attention; Executive function

Safe use of Ra-223 Radium Dichloride (223Ra) across a Wide-range of Clinical Scenarios: A 10-year Single-institution Radiation Safety Experience

223Ra is an effective therapeutic radiopharmaceutical for the treatment of prostate cancer metastatic to bone. As an institutional participant in the ALSYMPCA trial, and early adopter of Xofigo as a clinical modality, our facility has accrued over 10 years’ experience in the regulatory-compliant use of this radiopharmaceutical. Because 223Ra is a pure alpha emitter, there is negligible concern regarding external exposure from injected patients. However, several radiation safety related factors still need to be considered when treating patients with 223Ra. Our presentation will discuss a number of these concerns, based on first-hand experience gained from navigating several specific scenarios and additional information gathered from the medical literature, to provide guidance on the safe usage of 223Ra in the treatment of patients with boney metastases. Personnel involved in the clinical care and radiation safety oversight of patients treated with 223Ra were canvassed to recall cases with radiation safety concerns. By drawing upon our institution’s experience, and reviewing the relevant world-wide literature, we have provided guidance for various scenarios in the radiation-safety compliant treatment of patients with 223Ra. Physical, biological and regulatory aspects of 223Ra form the basis of understanding radiation safety concerns. We describe the potential of internal contamination from patient excreta, body fluids, and tissue samples based on a number of clinical scenarios, and the ensuing exposures that may result. Adherence to Universal Precautions is paramount in avoiding internal contamination. Of particular interest is our first-hand experience with a patient who underwent hip replacement surgery following 223Ra therapy, including the proper handling and storage of radioactive bone fragments. Handling of a deceased patient, and the associated guidelines regarding 223Ra decedents, is a potential outcome that should be familiar to physicians administering 223Ra therapy. While the lack of a gamma emission greatly reduces exposure and radiation concerns when treating patients with therapeutic levels of 223Ra activity, there are still several regulatory and safety concerns that need to be addressed in the course of potential patient scenarios. We will review appropriate solutions to these scenarios in a radiation-safety compliant manner.

Assessment of Complications Associated with Various Anesthetic Techniques in Patients Undergoing Hip Replacement Surgeries: A Retrospective Study

Background: Hip fracture in the elderly is a very common fracture, which mainly requires surgical treatment. Hence; we planned the present study to assess various complications associated with various anesthetic techniques in patients undergoing hip replacement surgeries. Subjects and Methods: Analysis of data files of a total of 160 patients was done.&nbsp; Retrieval of complete demographic and clinical data of all the subjects included in the present study was done.&nbsp; Recording of following parameter was done: Form of anaesthetics technique, Surgical procedure duration, and Fluid type and amount administered. Complication of the results was done by SPSS software. &nbsp;Results: Most commonly observed complications observed in the present study were hypotension, bleeding, embolism and cardiac arrest. Non- significant results were obtained while comparing the occurrence of complications among different study groups. Conclusion: Various types of anaesthetics techniques can be used with equal effectiveness among patients undergoing Hip replacement surgery.