AMPK/autophagy-mediated alleviation of tendinopathy by IL-38: A novel strategy for the treatment of obesity-related tendinopathy.

The effect of interleukin-38 (IL-38), a recently identified member of the IL-1 family with potential applications in various inflammation-related conditions, on ER stress has not been explored. Furthermore, its role in obesity-associated tendinopathy has not been investigated. In this study, human primary tenocytes were treated with palmitate (200 or 400 µM) and palmitate plus IL-38 (0-50 ng/mL) for 24 h. Western blotting was used to assess ER stress and tendinopathogenic markers in tenocytes. Monodansylcadaverine (MDC) staining was used to evaluate autophagosomes. Apoptosis was determined by cell viability assays, caspase 3 activity assays and TUNEL assays. Cell migration was evaluated by a cell scratch assay. Small interfering (si) RNA transfection was used for target gene silencing. Treatment of tenocytes with IL-38 attenuated apoptosis, restored the balance between MMPs and TIMP-1, and alleviated ER stress under palmitate conditions. IL-38 treatment enhanced AMPK phosphorylation and promoted the expression of autophagy markers related to LC3 conversion, p62 degradation, and autophagosome formation in cultured tenocytes. The effects of IL-38 on ER stress, apoptosis, and MMP-9, MMP-13, and TIMP-1 expression in palmitate-treated tenocytes were abrogated by AMPK siRNA or 3-methyladenine (3MA). These results suggest that IL-38 alleviates ER stress through the AMPK/autophagy pathway, thereby reducing apoptosis and preventing extracellular matrix (ECM) degradation in tenocytes under hyperlipidemic conditions. This study provides a promising therapeutic avenue for treating obesity-related tendinopathy using an endogenous compound such as IL-38.

Orthopedic postoperative infection profile and antibiotic sensitivity of 2038 patients across 24 countries - Call for region and institution specific surgical antimicrobial prophylaxis.

Purpose: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care. Methods: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East). Patients who developed orthopedic surgical site infection between January 2021 and December 2022 were included. Demographic details, bacterial profile of surgical site infection, and antibiotic sensitivity pattern were documented. Results: 2038 patients from 24 countries were included. Among them 69.7 % were male patients and 64.1 % were between 20 and 60 years. 70.3 % patients underwent trauma surgery and instrumentation was used in 93.5 %. Ceftriaxone was the most common preferred in 53.4 %. Early SSI was seen in 55.2 % and deep SSI in 59.7 %. Western Africa (76 %) and Asia-Pacific (52.8 %) reported a higher number of gram-negative infections whereas gram-positive organisms were predominant in other regions. Most common gram positive organism was Staphylococcus aureus (35 %) and gram-negative was Klebsiella (17.2 %). Majority of the organisms showed variable sensitivity to broad-spectrum antibiotics. Conclusion: Our study strongly proves that every institution has to analyse their surgical site infection microbiological profile and antibiotic sensitivity of the organisms and plan their surgical antimicrobial prophylaxis accordingly. This will help to decrease the rate of surgical site infection, prevent the emergence of multidrug resistance and reduce the economic burden of treatment.

Effectiveness of vancomycin powder for preventing postoperative spinal infection.

OBJECTIVE: This study aimed to assess the effectiveness of Vancomycin Power (VP) and the occurrence of resistant organisms after four-year of routine VP use. METHODS: The study included 1063 patients who underwent posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) between January 2010 and February 2020. Intrawound VP was applied to all instrumented fusions starting in January 2016. The patients were divided into two groups: those who did not apply VP (non-VP) (n = 605) between 2010 and 2015, and those who did apply VP (VP) (n = 458) between 2016 and 2020. The baseline characteristics, clinical symptoms, infection rate, and causative organisms were compared between the two groups. RESULTS: The rate of PSI was not significantly different between the non-VP group (1.32 %, n = 8) and the VP group (1.09 %, n = 5). Although adjusted by diabetes mellitus, VP still did not show statistical significance (OR = 0.757 (0.245-2.345), p = 0.630). There were no critical complications that were supposed to relation with vancomycin powder. In the 13 cases of PSI, seven pathogens were isolated, with a gram-negative organism identified in the non-VP group. However, the type of organism was not significantly different between the two groups. CONCLUSIONS: The use of intrawound VP may not affect the PSI and occurrence of resistant organism and may not cause critical complications. Therefore, clinicians may decide whether to use VP for preventing PSI not worrying about its safety.

Unstable Vancouver B1 periprosthetic femoral fracture fixation: A biomechanical comparison between a novel C-shaped memory alloy implant and cerclage wiring.

BACKGROUND: To compare the biomechanical stability of a novel, C-shaped nickel-titanium shape memory alloy (SMA) implant (C-clip) with traditional cerclage wiring in the fixation of a Vancouver B1 (VB1) periprosthetic femoral fracture (PFF). METHODS: In total, 18 synthetic femoral fracture models were constructed to obtain unstable VB1 fracture with an oblique fracture line 8 cm below the lesser trochanter. For each model, the distal portion was repaired using a 10-hole locking plate and four distal bi-cortical screws. The proximal portion was repaired using either three, threaded cerclage wirings or three, novel C-shaped implants. Specimens underwent biomechanical testing using axial compression, torsional and four-point bending tests. Each test was performed on three specimens. RESULTS: The C-clip was statistically significantly stronger (i.e., stiffer) than cerclage wiring in the three biomechanical tests. For axial compression, medians (ranges) were 39 (39-41) and 35 (35-35) N/mm, for the C-clip and cerclage wiring, respectively. For torsion, medians (ranges) were, 0.44 (0.44-0.45) and 0.30 (0.30-0.33) N/mm for the C-clip and cerclage wiring, respectively. For the four-point bending test, medians (ranges) were 39 (39-41) and 28 (28-31) N/mm; for the C-clip and cerclage wiring, respectively. CONCLUSION: Results from this small study show that the novel, C-shaped SMA appears to be biomechanically superior to traditional cerclage wiring in terms of stiffness, axial compression, torsion and four-point bending, and may be a valuable alternative in the repair of VB1 PFF. Further research is necessary to support these results.

DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells.

BACKGROUND: Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects of developmental endothelial locus-1 (DEL-1), a myokine upregulated during exercise, on endoplasmic reticulum (ER) stress-induced injury in retinal pigment epithelial cells. METHODS: We evaluated the levels of AMPK phosphorylation, autophagy markers, and ER stress markers in DEL-1-treated human retinal pigment epithelial cells (hRPE) using Western blotting. We also performed cell viability, caspase 3 activity assays, and autophagosome staining. RESULTS: Our findings showed that treatment with recombinant DEL-1 dose-dependently reduced the impairment of cell viability and caspase 3 activity in tunicamycin-treated hRPE cells. DEL-1 treatment also alleviated tunicamycin-induced ER stress markers and VEGF expression. Moreover, AMPK phosphorylation and autophagy markers were increased in hRPE cells in the presence of DEL-1. However, the effects of DEL-1 on ER stress, VEGF expression, and apoptosis in tunicamycin-treated hRPE cells were reduced by AMPK siRNA or 3-methyladenine (3-MA), an autophagy inhibitor. CONCLUSIONS: Our study suggests that DEL-1, a myokine, may have potential as a treatment strategy for AMD by attenuating ER stress-induced injury in retinal pigment epithelial cells.

Musclin Mitigates the Attachment of HUVECs to THP-1 Monocytes in Hyperlipidemic Conditions through PPARα/HO-1-Mediated Attenuation of Inflammation.

Musclin, a myokine, undergoes modulation during exercise and has demonstrated anti-inflammatory effects in cardiomyocytes and glomeruli. However, its role in atherosclerotic responses remains unclear. This study aimed to explore the impact of musclin on inflammatory responses and the interaction between endothelial cells and monocytes under hyperlipidemic conditions. The attachment levels of THP-1 monocytes on cultured HUVECs were examined. Inflammation and the expression of cell adhesion molecules were also evaluated. To explore the molecular mechanisms of musclin, PPARα or heme oxygenase 1 (HO-1) siRNA transfection was performed in HUVECs. The results revealed that treatment with recombinant musclin effectively suppressed the attachment of palmitate-induced HUVECs to THP-1 cells and reduced the expression of cell adhesion proteins (ICAM-1, VCAM-1, and E-selectin) in HUVECs. Furthermore, musclin treatment ameliorated the expression of inflammation markers (phosphorylated NFκB and IκB) in both HUVECs and THP-1 monocytes, as well as the release of TNFα and MCP-1 from HUVECs and THP-1 monocytes. Notably, musclin treatment augmented the expression levels of PPARα and HO-1. However, when PPARα or HO-1 siRNA was employed, the beneficial effects of musclin on inflammation, cell attachment, and adhesion molecule expression were abolished. These findings indicate that musclin exerts anti-inflammatory effects via the PPARα/HO-1 pathway, thereby mitigating the interaction between endothelial cells and monocytes. This study provides evidence supporting the important role of musclin in ameliorating obesity-related arteriosclerosis and highlights its potential as a therapeutic agent for treating arteriosclerosis.

Development and Verification of a 480 nm Blue Light Enhanced/Reduced Human-Centric LED for Light-Induced Melatonin Concentration Control.

With the inherent sleep and wake cycle regulated by natural sunlight, the human body has evolved over millennia to be active during the day and to rest at night. However, maintaining an optimal 24 h cycle has become increasingly problematic in modern society as more people spend the majority of the day indoors. Many research groups have reported that inadequate artificial lighting interferes with melatonin production and disrupts the circadian rhythm. This study considered biological functions for light-emitting diodes (LEDs) of next-generation illumination, and LED packages and spectra suitable for both daytime and nighttime applications were designed. The prepared daytime human-centric (HC)-LEDs had a melanopic/photopic (M/P) ratio that was up to 26% higher than that of conventional (c)-LEDs, whereas the nighttime HC-LEDs exhibited up to a 26% lower M/P ratio compared to the c-LEDs. Nevertheless, because the HC-LED is designed to have almost the same color coordinates as the c-LED having the same correlated-color temperature (CCT), there is no change in the perceived color. To substantiate the biological effect, melatonin level data were obtained from 22 voluntary participants in c- and HC-LED lighting environments. In the HC-LED lighting environment, melatonin was suppressed by 21.9% after waking, and nocturnal melatonin secretion was increased by up to 12.2%. As human-centric lighting, our HC-LEDs are expected to become an essential element for modern life, where people spend most of their time indoors.

CTRP4 attenuates apoptosis and epithelial-mesenchymal transition markers in podocytes through an AMPK/autophagy-dependent pathway.

Hyperglycemia, characterized by high blood glucose levels resulting from pancreatic beta cell dysfunction or impaired insulin signaling, is a contributing factor in the development of diabetic nephropathy. This study aimed to investigate the effects of C1q/TNF-related protein 4 (CTRP4), known for its anti-obesity and anti-inflammatory properties in various disease models, on podocyte apoptosis and endoplasmic reticulum (ER) stress in the presence of elevated glucose levels. The expression levels of various proteins in podocytes and adipocytes were evaluated by Western blotting. Autophagosomes in podocytes were stained by MDC. Chromatin condensation in podocytes was examined by Hoechst staining. The research revealed increased expression of CTRP4 in 3T3-L1 adipocytes and CIHP-1 podocytes exposed to high glucose (HG) conditions. Treatment with CTRP4 effectively mitigated HG-induced apoptosis and ER stress and normalized epithelial-to-mesenchymal transition (EMT) markers in CIHP-1 cells. Furthermore, elevated levels of AMPK phosphorylation and autophagy were observed in CIHP-1 cells treated with CTRP4. Silencing of AMPK or the use of 3-methyl adenine (3 MA) reduced the impacts of CTRP4 on apoptosis, EMT markers and ER stress in CIHP-1 cells. In conclusion, these findings suggest that CTRP4 alleviates ER stress in podocytes under hyperglycemic conditions, leading to the suppression of apoptosis and the restoration of EMT through AMPK/autophagy-mediated signaling. These insights provide valuable information for the development of therapeutic strategies for diabetic nephropathy.

Fundamental boundary matrices for 36 elementary boundary value problems of finite beam deflection on elastic foundation.

We consider the boundary value problem of finite beam deflection on elastic foundation with two point boundary conditions of the form $ u^{(p)}(-l) = u^{(q)}(-l) = u^{(r)}(l) = u^{(s)}(l) = 0 $, $ p < q $, $ r < s $, which we call elementary. We explicitly compute the fundamental boundary matrices corresponding to 7 special elementary boundary conditions called the dwarfs, and show that the fundamental boundary matrices for the whole 36 elementary boundary conditions can be derived from those for the seven dwarfs.

Madecassoside ameliorates hepatic steatosis in high-fat diet-fed mice through AMPK/autophagy-mediated suppression of ER stress.

Hepatic endoplasmic reticulum (ER) stress is a contributing factor in the development of hepatic steatosis in obesity. Madecassoside (MA), a pentacyclic triterpene derived from Centella asiatica, is known for its anti-inflammatory properties in the treatment of skin wounds. However, the impact of MA on hepatic ER stress and lipid metabolism in experimental obesity models has not been investigated. In this study, we examined the effects of MA on primary hepatocytes treated with palmitate and the livers of mice fed a high-fat diet (HFD). Our findings demonstrated that MA treatment reduced lipogenic lipid accumulation, apoptosis, and ER stress in hepatocytes. Additionally, MA treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and markers of autophagy. Importantly, when AMPK was inhibited by small interfering RNA (siRNA) or autophagy was blocked by 3-methyladenine (3MA), the protective effects of MA against ER stress, lipogenic lipid deposition, and apoptosis in palmitate-treated hepatocytes were abolished. These results suggest that MA mitigates hepatic steatosis in obesity through an AMPK/autophagy-dependent pathway. The present study highlights the potential of MA as a promising therapeutic candidate for hepatic steatosis.

Musclin attenuates lipid deposition in hepatocytes through SIRT7/autophagy-mediated suppression of ER stress.

Musclin, an exercise-responsive myokine, has the ability to attenuate inflammation, oxidative stress, and apoptosis in cardiomyocytes under pathogenic conditions. While the potential benefits of musclin in the cardiovascular system have been well documented, its effects on hepatic endoplasmic reticulum (ER) stress and lipid metabolism are not fully understood. The present study showed that musclin treatment reduced lipid accumulation and lipogenic protein expression in primary hepatocytes exposed to palmitate. Palmitate treatment led to an increase in markers of ER stress, which was reversed by musclin treatment. Musclin treatment increased SIRT7 expression and markers of autophagy in a dose-dependent manner. Small interfering (si) RNA of SIRT7 or 3-methyladenine (3 MA) reduced the effects of musclin on lipogenic lipid deposition in hepatocytes under hyperlipidemic conditions. These findings suggest that musclin can suppress palmitate-induced ER stress by upregulating SIRT7 and autophagy signaling, thereby alleviating lipid accumulation in primary hepatocytes. The current study provides a potential therapeutic strategy for the treatment of liver diseases characterized by lipid accumulation and ER stress, such as nonalcoholic fatty liver disease (NAFLD).

Adipokine gremlin-1 promotes hepatic steatosis via upregulation of ER stress by suppressing autophagy-mediated signaling.

Gremlin-1 (GR1) is a novel adipokine that is highly expressed in human adipocytes and has been shown to inhibit the BMP2/4-TGFb signaling pathway. It has an effect on insulin sensitivity. Elevated levels of Gremlin have been shown to lead to insulin resistance in skeletal muscle, adipocytes, and hepatocytes. In this study, we investigated the effect of GR1 on hepatic lipid metabolism under hyperlipidemic conditions and explored the molecular mechanisms associated with GR1 by in vitro and in vivo studies. We found that palmitate increased GR1 expression in visceral adipocytes. Recombinant GR1 increased lipid accumulation, lipogenesis, and ER stress markers in cultured primary hepatocytes. Treatment with GR1 increased EGFR expression and mTOR phosphorylation and reduced autophagy markers. EGFR or rapamycin siRNA reduced the effects of GR1 on lipogenic lipid deposition and ER stress in cultured hepatocytes. Administration of GR1 via the tail vein induced lipogenic proteins and ER stress while suppressing autophagy in the livers of experimental mice. Suppression of GR1 by in vivo transfection reduced the effects of a high-fat diet on hepatic lipid metabolism, ER stress, and autophagy in mice. These results suggest that the adipokine GR1 promotes hepatic ER stress due to the impairment of autophagy, ultimately causing hepatic steatosis in the obese state. The current study demonstrated that targeting GR1 may be a potential therapeutic approach for treating metabolic diseases, including metabolic-associated fatty liver disease (MAFLD).

Computed Tomography Evaluation of Percutaneous Pedicle Screws Inserted during Minimally Invasive Transforaminal Lumbar Interbody Fusion: Long-term Follow-up Results of Screw Violation.

Background: To evaluate the accuracy of percutaneous pedicle screw (PPS) insertion in degenerative lumbar disease treated with minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) and to analyze risk factors and long-term clinical outcomes of screw violation. Methods: Sixty-two consecutive patients (262 screws) were included. Based on postoperative computed tomography (CT) axial images, a PPS that perforated out of the pedicle was classified into a violation group, while screws surrounded by pedicular cortical bone were classified into a correct group. A logistic regression model was used for risk factor analysis of violation. We also observed the long-term clinical outcomes using the Oswestry disability index and visual analog scale. Results: Of the 262 screws, 14 (5.3%) were considered to be violated (10 medial violations and 4 lateral violations). All violations of S1 and L5 were in the medial direction. In contrast, entire violations of L4 were always lateral and of the 2 violations of L3, one was lateral and the other was medial. There were no cases of superior or inferior violation. The mean pedicle convergence angle (CA) was significantly higher in the violation group (mean ± standard deviation, 27.0° ± 6.2°) than in the correct group (21.7° ± 5.4°). There were no significant differences according to vertebral rotational angle, body mass index, bone mineral density, and surgical timing (learning curve) between the two groups. Logistic regression analyses demonstrated that a high CA was a significant risk factor for pedicle wall violation (p = 0.002). There were no significant differences in clinical or radiographic results between the two groups in 60 patients who were followed up for more than 1 year and in 40 patients who were followed up for more than 5 years. There were 2 patients who required reoperation to replace a screw due to leg pain. Conclusions: With PPS insertion during MI-TLIF, the rate of pedicle violation was 5.3% (14/262). An understanding of the anatomical characteristics of each vertebra and the unique structures of the patient is essential to prevent pedicle violations. Even in the violation group, PPS fixation was found to be a safe and useful procedure with successful long-term radiographic and clinical outcomes.

Oroxylin-A alleviates hepatic lipid accumulation and apoptosis under hyperlipidemic conditions via AMPK/FGF21 signaling.

Oroxylin-A (OA) is an O-methylated flavone that has been demonstrated to have anti-inflammatory properties in various disease models. However, the roles of OA in hepatic lipid metabolism and the specific molecular mechanisms by which it exerts these effects are not yet fully understood. In the current study, we aimed to investigate the effects of OA on hepatic lipid deposition and apoptosis, which play a pivotal role in the development of nonalcoholic fatty liver disease (NAFLD) in obesity in vitro models. We found that treatment with OA attenuated lipid accumulation, the expression of lipogenesis-associated proteins and apoptosis in palmitate-treated primary mouse hepatocytes. OA treatment suppressed phosphorylated NFκB and IκB expression in as well as TNFα and MCP-1 release from hepatocytes treated with palmitate. Treatment of hepatocytes with OA augmented AMPK phosphorylation and FGF21 expression. siRNA of AMPK or FGF21 abolished the effects of OA on inflammation as well as lipid accumulation and apoptosis in hepatocytes under palmitate treatment conditions. In conclusion, OA improves inflammation through the AMPK/FGF21 pathway, thereby attenuating lipid accumulation and apoptosis in hepatocytes. This study may help identify new targets for developing treatments for NAFLD.

Myokine musclin alleviates lipid accumulation in 3T3-L1 adipocytes through PKA/p38-mediated upregulation of lipolysis and suppression of lipogenesis.

Musclin (MUS), an exercise-responsive myokine, has been documented to attenuate inflammation and enhance physical endurance. However, the effects of MUS on differentiation and related molecular mechanisms in adipocytes have not yet been studied. In this study, we found that treatment with MUS attenuated lipid accumulation in fully differentiated 3T3-L1 cells. Furthermore, MUS treatment enhanced lipolysis assessed by glycerol release, and caused apoptosis, whereas it reduced the expression of lipogenic proteins, such as PPARγ and processed SREBP1. Treatment with MUS augmented phosphorylated PKA expression, whereas suppressed p38 phosphorylation in 3T3-L1 adipocytes. H89, a selective PKA inhibitor reduced the effects of MUS on lipogenic lipid accumulation as well as lipolysis except for apoptosis. These results suggest that MUS promotes lipolysis and suppresses lipogenesis through a PKA/p38-dependent pathway, thereby ameliorating lipid deposition in cultured adipocytes. The current study offers the potential of MUS as a therapeutic approach for treating obesity with few side effects.

Analysis of Factors Contributing to the Occurrence of Systemic Toxicity in Patients with Hydrofluoric Acid Skin Exposure Injury: An Individual Participant Data Meta-Analysis of 125 Clinical Cases from 1979 to 2020.

The purpose of this study is to analyze the factors contributing to the occurrence of systemic toxicity in patients injured after skin exposure to hydrofluoric acid (HFA) and to present guidelines for active treatment intervention based on this analysis. Data were acquired from EMBASE, PubMed, and Cochrane library for individual participant data (IPD) meta-analysis. Key searching terms included calcium gluconate (CAG), hydrofluoric acid, and case. This research consisted of case studies published between 1979 and 2020. Systemic toxicity was set as the main outcome. Data sets from 50 case studies (N = 125 participants) were analyzed. Multivariate binary logistic regression analyses of IPD found significant association effect of the total body surface area (TBSA) burned, indicating systemic toxicity [Regression coefficient estimate, 0.82; SE, 0.41; Odds ratio, 2.28; [95% confidence interval, 1.03-5.06], and p = 0.0424]. The optimal cutoff point (sensitivity; specificity) of the receiver operating characteristic curve of the total body surface area (TBSA) burned for contributing occurrence of systemic toxicity was 2.38(0.875; 0.959). IPD meta-analysis indicates that existing evidence supports the positive proportional association of the TBSA burned for systemic toxicity. If the TBSA burned (%) in patients exposed to hydrofluoric acid is greater than 2.38, early aggressive treatment intervention, including decontamination and various CAG application, should be recommended as the guideline.

Is Routine Use of Drain Really Necessary for Posterior Lumbar Interbody Fusion Surgery? A Retrospective Case Series with a Historical Control Group.

STUDY DESIGN: A retrospective case-control study. OBJECTIVES: The usefulness of a drain in spinal surgery has always been controversial. The purposes of this study were to determine the incidence of hematoma-related complications after posterior lumbar interbody fusion (PLIF) without a drain and to evaluate its usefulness. METHODS: We included 347 consecutive patients with degenerative lumbar disease who underwent single- or double-level PLIF. The participants were divided into 2 groups by the use of a drain or not; drain group and no-drain group. RESULTS: In 165 cases of PLIF without drain, there was neither a newly developed neurological deficit due to hematoma nor reoperation for hematoma evacuation. In the no-drain group, there were 5 (3.0%) patients who suffered from surgical site infection (SSI), all superficial, and 17 (10.3%) patients who complained of postoperative transient recurred leg pain, all treated conservatively. Days from surgery to ambulation and length of hospital stay (LOS) of the no-drain group were faster than those of the drain group (P < 0.001). In a multiple regression analysis, a drain insertion was found to have a significant effect on the delayed ambulation and increased LOS. No significant differences existed between the 2 groups in additional surgery for hematoma evacuation, or SSI. CONCLUSIONS: No hematoma-related neurological deficits or reoperations caused by epidural hematoma and SSI were observed in the no-drain group. The no-drain group did not show significantly more frequent postoperative complications than the drain use group, hence the routine insertion of a drain following PLIF should be reconsidered carefully.

Management of Osteoporotic Vertebral Fracture: Review Update 2022.

A vertebral fracture is the most common type of osteoporotic fracture. Osteoporotic vertebral fractures (OVFs) cause a variety of morbidities and deaths. There are currently few "gold standard treatments" outlined for the management of OVFs in terms of quantity and quality. Conservative treatment is the primary treatment option for OVFs. The treatment of pain includes short-term bed rest, analgesic medication, anti-osteoporotic medications, exercise, and a brace. Numerous reports have been made on studies for vertebral augmentation (VA), including vertebroplasty and kyphoplasty. There is still debate and controversy about the effectiveness of VA in comparison with conservative treatment. Until more robust data are available, current evidence does not support the routine use of VA for OVF. Despite the fact that the majority of OVFs heal without surgery, 15%-35% of patients with an unstable fracture, persistent intractable back pain, or severely collapsed vertebra that causes a neurologic deficit, kyphosis, or chronic pseudarthrosis frequently require surgery. Because no single approach can guarantee the best surgical outcomes, customized surgical techniques are required. Surgeons must stay current on developments in the osteoporotic spine field and be open to new treatment options. Osteoporosis management and prevention are critical to lowering the risk of future OVFs. Clinical studies on bisphosphonate's effects on fracture healing are lacking. Teriparatide was intermittently administered, which dramatically improved spinal fusion and fracture healing while lowering mortality risk. According to the available literature, there are no standard management methods for OVFs. More multimodal approaches, including conservative and surgical treatment, VA, and medications that treat osteoporosis and promote fracture healing, are required to improve the quality of the majority of guidelines.

Netrin-1 attenuates hepatic steatosis via UNC5b/PPARγ-mediated suppression of inflammation and ER stress.

AIMS: The current study investigated whether netrin-1 can attenuate hepatic steatosis through PPARγ/autophagy-mediated suppression of inflammation and endoplasmic reticulum (ER) stress in experimental animal models. MAIN METHODS: Hepatic steatosis was induced by a high-fat diet in experimental mice. Recombinant mouse netrin-1 was administered via the tail vein (1 µg/mouse, once every two days). Serum inflammatory cytokines and hepatic inflammatory and ER stress markers were determined in mice using ELISA and western blotting protocol. KEY FINDINGS: We found that netrin-1 expression was significantly increased (P < 0.05) in cultured macrophages treated with supernatants of subcutaneous adipocytes in the presence of palmitate and subcutaneous fat of obese mice. Recombinant netrin-1 treatment promoted PPARγ expression and autophagy, thereby attenuating inflammation and ER stress, lipid accumulation, and the expression of lipogenic proteins in mouse primary hepatocytes. High-fat diet (HFD) treatment increased hepatic inflammation and ER stress, causing hepatic steatosis in experimental mice. However, administration of netrin-1 reversed the effects of HFD on hepatic ER stress and lipid deposition. SIGNIFICANCE: These results suggest that subcutaneous adipose macrophage-derived netrin-1 ameliorates inflammation and ER stress in the liver, which in turn alleviates hepatic steatosis by enhancing basal PPARγ/autophagy-dependent signaling. The current study sheds light on the pathogenesis of hepatic steatosis in obesity and provides a promising therapeutic approach for treating metabolic-associated fatty liver disease (MAFLD).

Clinical differences between delayed and acute onset postoperative spinal infection.

ABSTRACT: Spine surgeons often encounter cases of delayed postoperative spinal infection (PSI). Delayed-onset PSI is a common clinical problem. However, since many studies have investigated acute PSIs, reports of delayed PSI are rare. The purpose of this study was to compare the clinical features, treatment course, and prognosis of delayed PSI with acute PSI.Ninety-six patients diagnosed with postoperative spinal infection were enrolled in this study. Patients were classified into 2 groups: acute onset (AO) within 90 days (n = 73) and delayed onset (DO) after 90 days (n = 23). The baseline data, clinical manifestations, specific treatments, and treatment outcomes were compared between the 2 groups.The history of diabetes mellitus (DM) and metallic instrumentation at index surgery were more DO than the AO group. The causative organisms did not differ between the 2 groups. Redness or heat sensation around the surgical wound was more frequent in the AO group (47.9%) than in the DO group (21.7%) (P = .02). The mean C-reactive protein levels during infection diagnosis was 8.9 mg/dL in the AO and 4.0 mg/dL in the DO group (P = .02). All patients in the DO group had deep-layer infection. In the DO group, revision surgery and additional instrumentation were required, and the duration of parenteral antibiotic use and total antibiotic use was significantly longer than that in the AO group. Screw loosening, disc space collapse, and instability were higher in the DO group (65.2%) than in the AO group (41.1%) (P = .04). However, the length of hospital stay did not differ between the groups.Delayed-onset PSI requires more extensive and longer treatment than acute-onset surgical site infection. Clinicians should try to detect the surgical site infection as early as possible.