Evaluating Pain Management from Peripheral Nerve Block for Geriatric Patients following Bipolar Hemiarthroplasty for Displaced Femoral-Neck Fracture.

INTRODUCTION: The purpose of this study was to evaluate peripheral nerve block (PNB) effectiveness in postoperative pain management and surgical outcomes for displaced femoral-neck fracture in geriatric patients (>70 years) who underwent bipolar hemiarthroplasty (BHA). METHODS: From January 2017 to December 2021, 231 geriatric patients with displaced femoral-neck fracture who consecutively underwent BHA were retrospectively reviewed. Patients were divided into two groups: the patient-controlled analgesia (PCA) group (n = 132) who received only intravenous (IV) PCA for postoperative pain management, and all others who received PNB with IV PCA (PNB+PCA) such as femoral nerve block or fascia iliaca compartment block after surgery (n = 99). Primary outcomes were postoperative visual analog scale (VAS) at rest and during activity at 6, 24, and 48 h postoperatively. Secondary outcomes were postoperative complications, changes in hemoglobin, length of hospital stay, and total morphine usage after surgery. RESULTS: Postoperative resting VAS at 6 h and 48 h was significantly lower in the PNB+PCA group compared with the PCA group (p = 0.075, p = 0.0318, respectively). However, there was no significant difference in either resting VAS at 24 h or active VAS. Complications of pneumonia and delirium until 1 month postoperative were significantly lower in the PNB + PCA group than the PCA group (p = 0.0022, p = 0.0055, respectively). CONCLUSION: PNB with IV PCA seems to have a beneficial effect on geriatric femoral-neck patients who underwent BHA with postoperative analgesia for reducing postoperative resting pain and complications, especially pneumonia and delirium.

Effect of Corticosteroid Use on the Occurrence and Progression of Osteonecrosis of the Femoral Head: A nationwide Nested Case-Control Study.

BACKGROUND: Although it is very well known that corticosteroids cause osteonecrosis of the femoral head (ONFH), it is unclear as to which patients develop ONFH. Additionally, there are no studies on the association between corticosteroid use and femoral head collapse in ONFH patients. We aimed to investigate the association between corticosteroid use and the risk of ONFH among the general population and what factors affect ONFH occurrence. Additionally, we aimed to demonstrate which factors affect femoral head collapse and total hip arthroplasty (THA) after ONFH occurrence. METHODS: A nationwide, nested case-control study was conducted with data from the National Health Insurance Service Physical Health Examination Cohort (2002 to 2019) in the Republic of Korea. We defined ONFH (N = 3,500) using diagnosis and treatment codes. Patients who had ONFH were matched 1:5 to form a control group based on the variables of birth year, sex, and follow-up duration. Additionally, in patients who have ONFH, we looked for risk factors for progression to THA. RESULTS: Compared with the control group, ONFH patients had a low household income and had more diabetes, hypertension, dyslipidemia, and heavy alcohol use (drinking more than 3 to 7 drinks per week). Systemic corticosteroid use (≥ 1,800 mg) was significantly associated with an increased risk of ONFH incidence. However, lipid profiles, corticosteroid prescription, and cumulative doses of corticosteroid did not affect the progression to THA. CONCLUSION: The ONFH risk increased rapidly when cumulative prednisolone use was ≥ 1,800 mg. However, oral or high-dose intravenous corticosteroid use and cumulative dose did not affect the prognosis of ONFH. Since the occurrence and prognosis of ONFH are complex and multifactorial processes, further study is needed.

STAT3 Decoy Oligodeoxynucleotides Suppress Liver Inflammation and Fibrosis in Liver Cancer Cells and a DDC-Induced Liver Injury Mouse Model.

Liver damage caused by various factors results in fibrosis and inflammation, leading to cirrhosis and cancer. Fibrosis results in the accumulation of extracellular matrix components. The role of STAT proteins in mediating liver inflammation and fibrosis has been well documented; however, approved therapies targeting STAT3 inhibition against liver disease are lacking. This study investigated the anti-fibrotic and anti-inflammatory effects of STAT3 decoy oligodeoxynucleotides (ODN) in hepatocytes and liver fibrosis mouse models. STAT3 decoy ODN were delivered into cells using liposomes and hydrodynamic tail vein injection into 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice in which liver injury was induced. STAT3 target gene expression changes were verified using qPCR and Western blotting. Liver tissue fibrosis and bile duct proliferation were assessed in animal experiments using staining techniques, and macrophage and inflammatory cytokine distribution was verified using immunohistochemistry. STAT3 decoy ODN reduced fibrosis and inflammatory factors in liver cancer cell lines and DDC-induced liver injury mouse model. These results suggest that STAT3 decoy ODN may effectively treat liver fibrosis and must be clinically investigated.

Risk factors for early septic failure after two-stage exchange total knee arthroplasty for treatment of periprosthetic joint infection.

BACKGROUND: The cause of early septic failure after two-stage exchange revision total knee arthroplasty (TKA) for chronic periprosthetic joint infection (PJI) and the factors affecting it are not well known. The purpose of this study was to determine the surgical outcomes and the risk factors for early septic failure after two-stage revision TKA for chronic PJI. METHODS: We identified a total of 246 adult patients who met the Musculoskeletal Infection Society (MSIS) diagnostic criteria for chronic PJI at two academic tertiary hospitals from March 2012 to December 2018. Finally, 151 patients who consecutively received two-stage exchange revision TKA for chronic PJI and who had a minimum 3-year follow-up were enrolled and retrospectively reviewed. Successful surgical treatment was evaluated for two-stage revision TKA and risk factors for early septic failure were identified. RESULTS: Early septic failures occurred within 3 years after reimplantation in 48 patients (31.8%). After accounting for potentially confounding variables, we found that male patient [odds ratio (OR): 2.753, 95% confidence interval (CI) 1.099-6.893, p = 0.031], fungus or mycobacterial infection (OR: 5.224, 95% CI 1.481-18.433, p = 0.01), and positive culture at reimplantation (OR: 4.407, 95% CI 1.255-15.480, p = 0.021) were independently associated with early septic failure after two-stage exchange revision TKA. CONCLUSION: Male patients, fungus or mycobacterial infection, and positive culture at reimplantation were independently associated with an increased risk of early septic failure after two-stage exchange revision TKA despite normal C-reactive protein values prior to reimplantation. Further prospective and high-quality studies are needed to determine the risk factors of two-stage exchange revision TKA for chronic PJI. LEVEL OF EVIDENCE: level IV; retrospective comparison; treatment study.

Antioxidant, Anti-Apoptotic, and Anti-Inflammatory Effects of Farrerol in a Mouse Model of Obstructive Uropathy.

Obstructive uropathy is a clinical condition that can lead to chronic kidney disease. However, treatments that can prevent the progression of renal injury and fibrosis are limited. Farrerol (FA) is a natural flavone with potent antioxidant and anti-inflammatory properties. Here, we investigated the effect of FA on renal injury and fibrosis in a mouse model of unilateral ureteral obstruction (UUO). Mice underwent a sham or UUO operation and received intraperitoneal injections of FA (20 mg/kg) daily for 8 consecutive days. Histochemistry, immunohistochemistry and immunofluorescence staining, TdT-mediated dUTP nick end labeling assay, Western blotting, gene expression analysis, and biochemical tests were performed. FA attenuated renal dysfunction (p < 0.05) and ameliorated renal tubular injury (p < 0.01) and interstitial fibrosis (p < 0.001) in UUO mice. FA alleviated 4-hydroxynonenal expression (p < 0.001) and malondialdehyde levels (p < 0.01) by regulating pro-oxidant and antioxidant enzymes. Apoptosis in the kidneys of UUO mice was inhibited by FA (p < 0.001), and this action was accompanied by decreased expression of cleaved caspase-3 (p < 0.01). Moreover, FA alleviated pro-inflammatory cytokine production (p < 0.001) and macrophage infiltration (p < 0.01) in the kidneys of UUO mice. These results suggest that FA ameliorates renal injury and fibrosis in the UUO model by inhibiting oxidative stress, apoptosis, and inflammation.

Silicone ring tourniquet could be a substitute for a conventional tourniquet in total knee arthroplasty with a longer surgical field: a prospective comparative study in simultaneous total knee arthroplasty.

INTRODUCTION: This study aimed to compare the clinical outcomes of silicon ring tourniquets and conventional pneumatic tourniquets in total knee arthroplasty (TKA). The study compared the operation time, total bleeding amount, length from the tourniquet distal end to the patella superior pole (L_TP), and complications related to the two tourniquet application methods and attempted to determine whether the silicon ring tourniquet has advantages over conventional pneumatic tourniquets. MATERIALS AND METHODS: This prospective comparative study included 30 patients who underwent bilateral simultaneous TKA for degenerative osteoarthritis in August to December 2021. All patients underwent TKA on one side with a conventional pneumatic tourniquet, while TKA on the other side with a silicon ring tourniquet. The primary outcomes were the L_TP, operation time, tourniquet time, total bleeding amount, total drainage amount, and postoperative visual analog scale (VAS) score of the tourniquet applied site at 6, 24, and 48 h postoperatively. The secondary outcome was tourniquet-related complications in both groups. RESULTS: L_TP was significantly longer in the silicon ring tourniquet group compared with that in the pneumatic tourniquet group (20.22 ± 2.74 cm versus 15.12 ± 2.40, p < 0.001). No significant difference was found in other results. The tourniquet applied site pain was less in the silicon ring tourniquet group (p = 0.037). CONCLUSIONS: Silicon ring tourniquet application resulted in better clinical outcomes than conventional pneumatic tourniquets in TKA. Because we can obtain a wider surgical field using silicon ring tourniquets without complications, silicon ring tourniquets could be a substitute for conventional pneumatic tourniquets in total knee arthroplasty or distal femoral surgeries.

Design of Piezoelectric Acoustic Transducers for Underwater Applications.

Interest in underwater transducers has persisted since the mid-1900s. Underwater transducers are designed in various shapes using various materials depending on the purpose of use, such as to achieve high power, improve broadband, and enhance beam steering. Therefore, in this study, an analysis is conducted according to the structural shape of the transducer, exterior material, and active material. By classifying transducers by structure, the transducer design trends and possible design issues can be identified. Researchers have constantly attempted new methods to improve the performance of transducers. In addition, a methodology to overcome this problem is presented. Finally, this review covers old and new research, and will serve as a reference for designers of underwater transducer.

Development of Multilayer Transducer and Omnidirectional Reflection Model for Active Reflection Control.

Underwater detection is accomplished using an underwater ultrasonic sensor, sound navigation and ranging (SONAR). Stealth to avoid detection by SONAR plays a major role in modern underwater warfare. In this study, we propose a smart skin that avoids detection by SONAR via controlling the signal reflected from an unmanned underwater vehicle (UUV). The smart skin is a multilayer transducer composed of an acoustic window, a double-layer receiver, and a single-layer transmitter. It separates the incident signal from the reflected signal from outside through the time-delay separation method and cancels the reflected wave from the phase-shifted transmission sound. The characteristics of the receiving and transmitting sensors were analyzed using a finite element analysis. Three types of devices were compared in the design of the sensors. Polyvinylidene fluoride (PVDF), which had little effect on the transmitted sound, was selected as the receiving sensor. A stacked piezoelectric transducer with high sensitivity compared to a cymbal transducer was used as the transmitter. The active reflection control system was modeled and verified using 2D 360° reflection experiments. The stealth effect that could be achieved by applying a smart skin to a UUV was presented through an active reflection-control omnidirectional reflection model.

Preoperative Carbohydrate Drink Intake Increases Glycemic Variability in Patients with Type 2 Diabetes Mellitus in Total Joint Arthroplasty: A Prospective Randomized Trial.

BACKGROUND: Preoperative carbohydrate treatment attenuates insulin resistance and improves metabolism to an anabolic state. Despite these benefits, impaired glycemic control and aspiration risk related to gastroparesis represent concerns for patients with diabetes undergoing surgery. This randomized controlled trial investigated the effects of oral carbohydrate therapy on perioperative glucose variability, metabolic responses, and gastric volume in diabetic patients undergoing elective total hip or knee arthroplasty. METHODS: Fifty diabetic patients scheduled to undergo elective total knee or hip arthroplasty during August 2019-October 2020 were randomly assigned to a control or carbohydrate therapy (CHO) group. CHO group of patients received a 400-mL carbohydrate drink 2-3 h before anesthesia; control group of patients underwent overnight fasting from midnight, one night before surgery. Blood glucose levels were measured before intake of the carbohydrate drink, before spinal anesthesia, preoperatively, immediately postoperatively, and 1 h postoperatively. Insulin level and gastric volume were measured before spinal anesthesia. RESULTS: The glucose variability of patients in the CHO group was significantly higher than that of those in the control group (16.5 vs. 10.1%, P = 0.008). Similarly, insulin resistance was higher in the CHO group than in the control group (8.5 vs. 2.7, P < 0.001). The gastric volume did not differ significantly between the groups (61.3 vs. 15.2 ml, P = 0.082). CONCLUSIONS: Preoperative oral carbohydrate therapy increases glucose variability and insulin resistance in diabetic patients. Therefore, carbohydrate beverages should be cautiously administered to diabetic patients, considering metabolic and safety aspects. Trial registration number ClinicalTrials.gov (No. NCT04013594).

Difference between medial and lateral tibia plateau in the coronal plane: importance of preoperative evaluation for medial unicompartmental knee arthroplasty.

BACKGROUND: Setting bone cutting levels for different joint line orientations of the medial and lateral tibia plateaus in individual patients is not clear. We aimed to evaluate the difference between joint line orientation of the medial and lateral tibia plateaus relative to the horizontal line of mechanical axis of tibia as tibial plateau difference (TPD) for an optimal tibial bone cut in medial unicompartmental knee arthroplasty (UKA) and determine which factors could influence TPD. We aimed to investigate the effect of preoperative TPD on polyethylene liner size in medial UKA. METHODS: TPD in the coronal plane were measured in 181 female patients (181 knees). To determine the morphology of proximal tibia according to the severity of osteoarthritis, the patients were classified into three groups based on diagnosis and treatment: 80 who underwent robot-assisted medial UKA, 45 who underwent total knee arthroplasty (TKA), and 56 with early-stage osteoarthritis (OA) who had conservative management. Also, we divided the medial UKA group into two groups according to TPD (greater than or less than 5 mm) and compared polyethylene liner sizes. RESULTS: No significant difference was observed in TPD (p = 0.662), difference between the medial and lateral femoral condyle levels (p = 0.54), medial proximal tibial angle (p = 0.169), or posterior tibial slope (p = 0.466) among the three groups. Increased TPD was significantly associated with increased mechanical femorotibial angle(mFTA) (p < 0.01). The medial UKA group was divided into two groups according to TPD greater or less than 5 mm. Thicker polyethylene liners were used for groups with TPD greater than 5 mm (8.5 ± 0.7 mm versus 8.2 ± 0.3 mm, p = 0.01). Additionally, the proportion of patients using the thinnest polyethylene (8 mm) in each TPD group (greater or less than 5 mm) was higher in patients with TPD less than 5 mm (82.4% versus 58.7%, p = 0.038). CONCLUSIONS: Preoperative measurement of TPD is important to help surgeons predict the most appropriate bone cutting level in the coronal plane in primary medial UKA. Tibial bone resection would be likely to be thicker than needed in patients with increased TPD in medial UKA.

Increasing the transmission efficiency of transcranial ultrasound using a dual-mode conversion technique based on Lamb waves.

Transcranial focused ultrasound (FUS) is a noninvasive treatment for brain tumors and neuromodulation. Based on normal incidence, conventional FUS techniques use a focused or an array of ultrasonic transducers to overcome the attenuation and absorption of ultrasound in the skull; however, this remains the main limitation of using FUS. A dual-mode conversion technique based on Lamb waves is proposed to achieve high transmission efficiency. This concept was validated using the finite element analysis (FEA) and experiments based on changes in the incident angle. Aluminum, plexiglass, and a human skull were used as materials with different attenuations. The transmission loss was calculated for each material, and the results were compared with the reflectance function of the Lamb waves. Oblique incidence based on dual-mode conversion exhibited a better transmission efficiency than that of a normal incidence for all of the specimens. The total transmission losses for the materials were 13.7, 15.46, and 3.91 dB less than those associated with the normal incidence. A wedge transducer was designed and fabricated to implement the proposed method. The results demonstrated the potential applicability of the dual-mode conversion technique for the human skull.

Acetabular labral tear is associated with high pelvic incidence with or without femoroacetabular impingement morphology.

PURPOSE: The aim of this study was to investigate the association between pelvic sagittal parameters and acetabular labral tears. METHODS: Three-hundred and sixty-five patients (449 hips) who underwent magnetic resonance imaging (MRI) or magnetic resonance arthrogram (MRA) for hip pain were enrolled in this study. Pelvic sagittal parameters, including the pelvic incidence, pelvic tilt, and sacral slope, were measured with a standing lumbosacral lateral radiograph. All subjects were divided into two groups according to the presence or absence of radiologic acetabular labral tears and compared. Furthermore, the two groups were divided into subgroups according to whether femoroacetabular impingement (FAI) morphology was present or not and compared. RESULTS: Pelvic incidence was greater in the labral tear group than in the non-labral tear group (52.3° ± 8.2° versus 47.1° ± 6.8°, p < 0.001). After accounting for potentially confounding variables, we found that higher age (odds ratio 1.04, 95% confidence interval [CI] 1.02 to 1.06, p = 0.001), FAI (odds ratio 15.11, 95% CI 7.43 to 30.75, p < 0.001), and high pelvic incidence (odds ratio 1.13, 95% CI 1.09 to 1.17, p < 0.001) were independently associated with acetabular labral tear. When only the patients without FAI (308 hips) were divided into groups with and without acetabular labral tear, we found that higher age (odds ratio 1.03, 95% CI 1.01 to 1.06, p = 0.008) and high pelvic incidence (odds ratio 1.15, 95% CI 1.11 to 1.19, p < 0.001) were independently associated with acetabular labral tear. CONCLUSION: Acetabular labral tear is associated with high pelvic incidence with or without FAI morphology. LEVEL OF EVIDENCE: III.

Effects of Apamin on MPP+-Induced Calcium Overload and Neurotoxicity by Targeting CaMKII/ERK/p65/STAT3 Signaling Pathways in Dopaminergic Neuronal Cells.

Parkinson's disease (PD), a neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons. The pathogenesis of PD is associated with several factors including oxidative stress, inflammation, and mitochondrial dysfunction. Ca2+ signaling plays a vital role in neuronal signaling and altered Ca2+ homeostasis has been implicated in many neuronal diseases including PD. Recently, we reported that apamin (APM), a selective antagonist of the small-conductivity Ca2+-activated K+ (SK) channel, suppresses neuroinflammatory response. However, the mechanism(s) underlying the vulnerability of DA neurons were not fully understood. In this study, we investigated whether APM affected 1-methyl-4-phenyl pyridinium (MPP+)-mediated neurotoxicity in SH-SY5Y cells and rat embryo primary mesencephalic neurons. We found that APM decreased Ca2+ overload arising from MPP+-induced neurotoxicity response through downregulating the level of CaMKII, phosphorylation of ERK, and translocation of nuclear factor NFκB/signal transducer and activator of transcription (STAT)3. Furthermore, we showed that the correlation of MPP+-mediated Ca2+ overload and ERK/NFκB/STAT3 in the neurotoxicity responses, and dopaminergic neuronal cells loss, was verified through inhibitors. Our findings showed that APM might prevent loss of DA neurons via inhibition of Ca2+-overload-mediated signaling pathway and provide insights regarding the potential use of APM in treating neurodegenerative diseases.

Anti-Fibrotic Effect of Synthetic Noncoding Decoy ODNs for TFEB in an Animal Model of Chronic Kidney Disease.

Despite emerging evidence suggesting that autophagy occurs during renal interstitial fibrosis, the role of autophagy activation in fibrosis and the mechanism by which autophagy influences fibrosis remain controversial. Transcription factor EB (TFEB) is a master regulator of autophagy-related gene transcription, lysosomal biogenesis, and autophagosome formation. In this study, we examined the preventive effects of TFEB suppression on renal fibrosis. We injected synthesized TFEB decoy oligonucleotides (ODNs) into the tail veins of unilateral ureteral obstruction (UUO) mice to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and collagen was decreased by TFEB decoy ODN. Additionally, TEFB ODN administration inhibited the expression of microtubule-associated protein light chain 3 (LC3), Beclin1, and hypoxia-inducible factor-1α (HIF-1α). We confirmed that TFEB decoy ODN inhibited fibrosis and autophagy in a UUO mouse model. The TFEB decoy ODNs also showed anti-inflammatory effects. Collectively, these results suggest that TFEB may be involved in the regulation of autophagy and fibrosis and that regulating TFEB activity may be a promising therapeutic strategy against kidney diseases.

Bee Venom and Its Major Component Melittin Attenuated Cutibacterium acnes- and IGF-1-Induced Acne Vulgaris via Inactivation of Akt/mTOR/SREBP Signaling Pathway.

Acne vulgaris is the most common disease of the pilosebaceous unit. The pathogenesis of this disease is complex, involving increased sebum production and perifollicular inflammation. Understanding the factors that regulate sebum production is important in identifying novel therapeutic targets for the treatment of acne. Bee Venom (BV) and melittin have multiple effects including antibacterial, antiviral, and anti-inflammatory activities in various cell types. However, the anti-lipogenic mechanisms of BV and melittin have not been elucidated. We investigated the effects of BV and melittin in models of Insulin-like growth factor-1 (IGF-1) or Cutibacterium acnes (C. acnes)-induced lipogenic skin disease. C. acnes or IGF-1 increased the expression of sterol regulatory element-binding protein-1 (SREBP-1) and proliferator-activated receptor gamma (PPAR-γ), transcription factors that regulate numerous genes involved in lipid biosynthesis through the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/SREBP signaling pathway. In this study using a C. acnes or IGF-1 stimulated lipogenic disease model, BV and melittin inhibited the increased expression of lipogenic and pro-inflammatory factor through the blockade of the Akt/mTOR/SREBP signaling pathway. This study suggests for the first time that BV and melittin could be developed as potential natural anti-acne agents with anti-lipogenesis, anti-inflammatory, and anti-C. acnes activity.

Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model.

The global burden of chronic kidney disease is increasing, and the majority of these diseases are progressive. Special site-targeted drugs are emerging as alternatives to traditional drugs. Oligonucleotides (ODNs) have been proposed as effective therapeutic tools in specific molecular target therapies for several diseases. We designed ring-type non-coding RNAs (ncRNAs), also called mTOR ODNs to suppress mammalian target rapamycin (mTOR) translation. mTOR signaling is associated with excessive cell proliferation and fibrogenesis. In this study, we examined the effects of mTOR suppression on chronic renal injury. To explore the regulation of fibrosis and inflammation in unilateral ureteral obstruction (UUO)-induced injury, we injected synthesized ODNs via the tail vein of mice. The expression of inflammatory-related markers (interleukin-1ß, tumor necrosis factor-α), and that of fibrosis (α-smooth muscle actin, fibronectin), was decreased by synthetic ODNs. Additionally, ODN administration inhibited the expression of autophagy-related markers, microtubule-associated protein light chain 3, Beclin1, and autophagy-related gene 5-12. We confirmed that ring-type ODNs inhibited fibrosis, inflammation, and autophagy in a UUO mouse model. These results suggest that mTOR may be involved in the regulation of autophagy and fibrosis and that regulating mTOR signaling may be a therapeutic strategy against chronic renal injury.

Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal Injury.

Renal fibrosis is a common process of various kidney diseases. Autophagy is an important cell biology process to maintain cellular homeostasis. In addition, autophagy is involved in the pathogenesis of various renal disease, including acute kidney injury, glomerular diseases, and renal fibrosis. However, the functional role of autophagy in renal fibrosis remains poorly unclear. The mammalian target of rapamycin (mTOR) plays a negative regulatory role in autophagy. Signal transducer and activator of transcription 3 (STAT3) is an important intracellular signaling that may regulate a variety of inflammatory responses. In addition, STAT3 regulates autophagy in various cell types. Thus, we synthesized the mTOR/STAT3 oligodeoxynucleotide (ODN) to regulate the autophagy. The aim of this study was to investigate the beneficial effect of mTOR/STAT3 ODN via the regulation of autophagy appearance on unilateral ureteral obstruction (UUO)-induced renal fibrosis. This study showed that UUO induced inflammation, tubular atrophy, and tubular interstitial fibrosis. However, mTOR/STAT3 ODN suppressed UUO-induced renal fibrosis and inflammation. The autophagy markers have no statistically significant relation, whereas mTOR/STAT3 ODN suppressed the apoptosis in tubular cells. These results suggest the possibility of mTOR/STAT3 ODN for preventing renal fibrosis. However, the role of mTOR/STAT3 ODN on autophagy regulation needs to be further investigated.

Fall Patterns Predict Mortality After Hip Fracture in Older Adults, Independent of Age, Sex, and Comorbidities.

Falls are the most frequent cause of hip fracture. We aimed to investigate whether specific fall patterns have predictive value for mortality after hip fracture. In this cohort study, data of individuals presented to the Severance Hospital, Seoul, Korea, between 2005 and 2019 due to fragility hip fracture (n = 1986) were analyzed. Fall patterns were defined as causes, activities leading to falls, and a combination of both, based on electronic medical records using pre-specified classification from a prior study on video-captured falls. Mean age of study subjects were 77 years (71% women) and 211 patients (10.6%) died during follow-up (median 544 days). Indoor falls at home had a higher mortality than outdoor falls (11.9 vs. 8.0%, p = 0.009). Among 16 fall patterns, incorrect weight shift while sitting down (adjusted hazard ratio [aHR] 4.03) or getting up (aHR 2.01), collapse during low-risk activity (aHR 2.39), and slipping while walking (aHR 2.90, p < 0.01 for all) were associated with increased mortality compared to outdoor falls, after adjustment for age, sex, and Charlson comorbidity index (CCI), constituting a high-risk pattern. High-risk fall patterns were associated with a higher risk of mortality (aHR 2.56, p < 0.001) than low-risk patterns (aHR 1.37, p = 0.080) and outdoor falls (referent; log rank p < 0.001), which improved mortality prediction when added to a base model including age, sex, and CCI (integrative area under receiver-operating characteristics curve 0.675 to 0.698, p < 0.001). Specific fall patterns were associated with higher mortality in older adults with hip fracture, independent of age, sex, and comorbidities.

Anti-fibrotic effects of synthetic TGF-ß1 and Smad oligodeoxynucleotide on kidney fibrosis in vivo and in vitro through inhibition of both epithelial dedifferentiation and endothelial-mesenchymal transitions.

Kidney fibrosis is a common process of various kidney diseases leading to end-stage renal failure irrespective of etiology. Myofibroblasts are crucial mediators in kidney fibrosis through production of extracellular matrix (ECM), but their origin has not been clearly identified. Many study proposed that epithelial and endothelial cells become myofibroblasts by epithelial dedifferentiation and endothelial-mesenchymal transition (EndoMT). TGF-ß1/Smad signaling plays a crucial role in partly epithelial-mensencymal transition (EMT) and EndoMT. Thus, we designed the TGF-ß1/Smad oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequence for Smad transcription factor and TGF-ß1 mRNA. Therefore, this study investigated the anti-fibrotic effect of synthetic TGF-ß1/Smad ODN on UUO-induced kidney fibrosis in vivo model and TGF-ß1-induced in vitro model. To examine the effect of TGF-ß1/Smad ODN, we performed various experiments to evaluate kidney fibrosis. The results showed that UUO induced inflammation, ECM accumulation, epithelial dedifferentiation and EndoMT processes, and tubular atrophy. However, synthetic TGF-ß1/Smad ODN significantly suppressed UUO-induced fibrosis. Furthermore, synthetic ODN attenuated TGF-ß1-induced epithelial dedifferentiation and EndoMT program via blocking TGF-ß1/Smad signaling. In conclusion, this study demonstrated that administration of synthetic TGF-ß1/Smad ODN attenuates kidney fibrosis, epithelial dedifferentiation, and EndoMT processes. The findings propose the possibility of synthetic ODN as a new effective therapeutic tool for kidney fibrosis.

Anatomical tibial component is related to more medial tibial stress shielding after total knee arthroplasty in Korean patients.

PURPOSE: This study aimed to investigate stress shielding of anatomical tibial components (ATCs) in comparison to conventional symmetric tibial components (STCs) in Korean patients which may be related to medial tibial bone loss. METHOD: 78 knees in 59 patients with ATCs (Persona™) and 74 knees in 58 patients with STCs (NexGen LPS-Flex™) were retrospectively reviewed. Radiographic parameters and clinical outcomes in both groups were compared. Logistic regression analysis was performed to identify risk factors for medial tibial bone loss. RESULTS: Medial tibial bone loss was significantly greater in the ATC group (1.6 ± 1.3 mm) than in the STC group (0.4 ± 0.8 mm) (p < 0.001). The ATC group showed a shorter distance between the distal metal tip and anteromedial cortex and higher invading into the sclerotic bone lesion (ISBL) than the STC group (p = 0.034 and p = 0.044, respectively). Multiple logistic regression analysis suggested ATC, a shorter distance to the anteromedial cortex, and the presence of ISBL as risk factors for medial tibial bone loss. The odds ratios of medial tibial bone loss according to type of prosthesis, distance to anteromedial cortex, and presence of ISBL were 6.25 (range 2.86-13.63, p < 0.001), 0.69 (range 0.51-0.93, p = 0.015), and 3.79 (range 1.56-9.21, p = 0.003), respectively. Notwithstanding, there was no difference in clinical outcomes between the two groups. CONCLUSION: In Korean patients, ATCs potentially causes greater medial tibial bone loss due to stress shielding than STCs. The design, however, does not yet appear to affect clinical outcomes at mid-term follow-up. LEVEL OF EVIDENCE: Retrospective cohort study, level III.