Correlation of High-Grade Osteosarcoma Response to Chemotherapy with Enhanced Tissue Immunological Response: Analysis of CD95R, IFN-γ, Catalase, Hsp70, and VEGF.

High-grade osteosarcoma, a primary malignant bone tumour, is experiencing a global increase in reported incidence with varied prevalence. Despite advances in management, which include surgery and neoadjuvant chemotherapy often an unsatisfactory outcome is found due to poor or heterogeneous response to chemotherapy. Our study delved into chemotherapy responses in osteosarcoma patients and associated molecular expressions, focusing on CD95 receptor (CD95R), interferon (IFN)-γ, catalase, heat-shock protein (Hsp)70, and vascular endothelial growth factor (VEGF). Employing immunohistochemistry and Huvos grading of post-chemo specimens, we analysed formalin-fixed paraffin-embedded (FFPE) osteosarcoma tissue of resected post-chemotherapy specimens from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia (DSGAH), spanning from 2016 to 2020. Results revealed varied responses (poor 40.38%, moderate 48.08%, good 11.54%) and distinct patterns in CD95R, IFN-γ, catalase, Hsp70, and VEGF expression. Significant differences among response groups were observed in CD95R and IFN-γ expression in tumour-infiltrating lymphocytes. The trend of diminishing CD95R expression from poor to good responses, accompanied by an increase in IFN-γ, implied a reduction in the count of viable osteosarcoma cells with the progression of Huvos grading. Catalase expression in osteosarcoma cells was consistently elevated in the poor response group, while Hsp70 expression was highest. VEGF expression in macrophages was significantly higher in the good response group. In conclusion, this study enhances our understanding of immune-chemotherapy interactions in osteosarcoma and identifies potential biomarkers for targeted interventions.

Patellofemoral functional outcome of gracilis sparing compared to gracilis sacrificing ACL reconstruction.

Introduction: The hamstring is the most popular autograft used for anterior cruciate ligament reconstruction (ACLR). Despite its excellent outcome, donor site morbidity is also irritating. Patellofemoral problems are reported to be one of the side effects after hamstring autograft harvesting, suggested to be due to both gracilis & semitendinosus sacrificing. Some experts propose retaining gracilis to decrease patellofemoral problems. The all-inside technique is an advantageous ACLR technique that can preserve the gracilis muscle while reducing muscle strength loss of affected limbs and the risk of knee joint instability under rotational load. This study aims to compare the patellofemoral functional outcome of both gracilis sparing and sacrificing using a validated Kujala score three months after ACLR. Methods: There was total of 20 subjects who underwent ACLR between December 2021 and May 2022 and met the inclusion criteria. They were then grouped into gracilis sparing group (n = 10) and gracilis sacrificing group (n = 10). Follow up assessment (Kujala Score) was conducted during phase II of the rehabilitation program. The assessed variables were surgery technique, time of surgery-to-evaluation, and Kujala Score. Result: There were no significant differences in Kujala Score between gracilis sparing and gracilis sacrificing groups (p = 0.809). There was a strong positive correlation between the time of surgery-to-evaluation and Kujala Score in each group (p = 0.942 and p = 0.910, respectively). Conclusion: There are no differences in patellofemoral functional outcomes between patients who undergo gracilis sparing and gracilis sacrificing ACLR with good scores of Kujala, which means both gracilis sparing and sacrificing show no harm to the patellofemoral after the ACLR.

Implant surface modifications as a prevention method for periprosthetic joint infection caused by Staphylococcus aureus: a systematic review and meta-analysis.

Background: Periprosthetic joint infection is the most common infection due to joint replacement. It has been reported that, over a 5-year time span, 3.7 % of cases occurred annually. This statistic has increased to 6.86 % over 16 years. Thus, an effective method is required to reduce these complications. Several strategies such as coating methods with various materials, such as antibiotics, silver, and iodine, have been reported. However, the best preventive strategy is still undetermined. Therefore, this systematic review aims to evaluate the outcome of coating methods on joint arthroplasty as a treatment or preventive management for infection complications. Methods: Eligible articles were systematically searched from multiple electronic databases (PubMed, Cochrane library, and ScienceDirect) up to 2 June 2022. Based on the criterion inclusion, eight articles were selected for this study. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the study, and the meta-analysis test was conducted with Review Manager 5.4. Results: The quality of the articles in this study is in the range of moderate to good. It was found that the application of modified antibiotic coatings significantly reduced the occurrence of periprosthetic joint infection (PJI) ( p 0.03), and silver coating could not significantly ( p 0.47) prevent the occurrence of PJI. However, according to the whole aspect of coating modification, the use of antibiotics, silver, and iodine can minimize the occurrence of PJI ( p   < 0.0001 ). Conclusion: Coating methods using antibiotics are an effective method that could significantly prevent the occurrence of PJI. On the other hand, coating with non-antibiotic materials such as silver could not significantly prevent the incidence of PJI.

Plating technique outcome evaluation in calcaneal fracture based on American orthopaedics foot and ankle score and Böhler-Gissane angle: A case series.

INTRODUCTION: Intraarticular Calcaneal fracture treatment nowadays is still up for debate. Surgical plating treatment is favorable because of the rapid healing process and better anatomical reduction despite the invasive intervention. Hence, clinical evaluation is needed to assess the quality-of-life index from foot and ankle by the American orthopaedics Foot and Ankle Society (AOFAS) score postoperatively. Then, the outcome evaluation of reduction in calcaneal plating of intraarticular calcaneal fracture with Böhler angle and Gissane angle to see if the calcaneal plating technique is a recommended treatment for the calcaneal fracture. METHODS: We treated six patients from December 2020-July 2021 with a calcaneal fracture that underwent surgical plating, mainly by one surgeon. A calcaneal fracture is classified according to sanders classification. In this study, four patients are above the age of 40, and two are under 25. Pre-operative Böhler angle ranged from 8 to 65°, and Gissane angle ranged from 134 to 158°. OUTCOMES: Surgical plating was performed on all six patients. From clinical evaluation using the AOFAS score, we got satisfactory results on all patients who underwent calcaneal plating surgery. Three patients achieved excellent range outcomes with 95% and 99% of AOFAS Scores, and three patients reported AOFAS score good range outcomes with the lowest score of 88%. From the radiological outcome, most of the patient's Böhler and Gissane angles achieved normal value after surgical plating. CONCLUSION: The calcaneal plating technique gives better anatomical reduction depending on Bohler and Gissane angle. These results promise that anatomical reduction can improve clinical outcomes based on the AOFAS score. Thus, the plating method can be used effectively to treat an intraarticular calcaneal fracture.

Superconstructs in reconstruction surgery of Charcot foot Brodsky 1: A case report.

INTRODUCTION: Charcot neuropathic osteoarthropathy (CN) is a chronic, progressive condition of joints, soft tissues, and bones. CN causes considerable high mortality and morbidity. A common issue is early diagnosis and appropriate treatment. Thus, the operative treatment is indicated when patients have progressive deformities, infection and ulceration. The superconstructs method for Charcot foot (CF) is considered giving better clinical outcome than other methods. PRESENTATION OF CASE: A 61-year-old male admitted to an outpatient clinic with chief complaint of swelling and pain on a left foot with history of diabetes mellitus type 2. From the physical examination, left foot revealed a swelling with rocker bottom deformity and limited range of motion. The radiological examination showed sclerotic appearance of bone deformity metatarsal joint of midfoot of toe. The patients were diagnosed with left Charcot foot Brodsky Type 1, Eichenholtz grade III with diabetes mellitus type 2. DISCUSSION: We made superconstructs rather than standard fixation which is frequently inadequate due to changes accompanying the Charcot process. Thus, we performed an adequate reduction of deformity, reduce soft tissue tension, fixation extension beyond a zone of injury, then use of strongest fixation devices that are applied to maximize mechanical function. CONCLUSION: This study showed that superconstructs provide satisfactory clinical and outcomes. This method is useful for achieving construct and stable fixation especially for Charcot foot.

Unusual combination of posterior cruciate ligament tibial avulsion fracture and Segond fracture: A case report.

INTRODUCTION AND IMPORTANCE: Posterior cruciate ligament (PCL) avulsion fracture is an uncommon entity, but it poses significant morbidity to patient's knee and activities. A combination of PCL avulsion fracture with Segond fracture is rare and has not been described much before in known literature. In this case report, we present a rare case of a combination of these two injuries. CASE PRESENTATION: A 16-year-old cyclist who sustained left knee injury after a high-velocity fall while cycling. He fell with his anteromedial side of his left knee hitting the ground in flexion. After the fall, he felt excruciating pain and unable to bear weight. Examination revealed severe joint effusion, tenderness on posterior and lateral side of the left knee, no vascular injury and neurological deficit present. Radiographic examination revealed PCL avulsion fracture and Segond fracture. Five days after the injury, the avulsed PCL fragment and the lateral tibial plateau fragment were reduced and fixed with 3.5 mm cortical screw and washers. On the follow up, the patient stated that there is no pain on weightbearing position and after evaluated with Knee injury and Osteoarthritis Outcome Score (KOOS), the result is 90%. CLINICAL DISCUSSION: Although the combination of PCL avulsion fracture and Segond fracture is rare, this pattern of injury could happen and could be considered when evaluating knee injuries. CONCLUSION: Both fractures need to be addressed and managed adequately to restore knee stability and prevent early joint degeneration.

Double posterior lateral plating arthrodesis for charcot ankle: A case series.

INTRODUCTION: Ankle arthrodesis is one of the managements for a significantly unstable Charcot ankle. Some of the methods of internal fixation for ankle arthrodesis include the use of intramedullary nails, screws, and plates. Ankle arthrodesis using intramedullary nails has become more popular. However, studies evaluating the use of plate fixation, particularly double posterior lateral plating, are limited. We report the clinical and radiological outcomes of double posterior lateral plating ankle arthrodesis in three diabetic Charcot ankle patients. PRESENTATION OF CASE: Three patients, aged 73, 67, and 65 years old, complained of ankle pain and with a history of type 2 diabetes mellitus. The physical examination revealed swelling and erythema without a sign of active infection. The radiological examination showed ankle deformity, and the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot scores were 5, 10, and 0, respectively. All patients were diagnosed with a diabetic Charcot ankle and underwent ankle arthrodesis using double posterior lateral plating. Four months and six months follow up revealed talus union, improved ankle deformity, and improved AOFAS Ankle-Hindfoot scores to 70, 76, and 73, respectively. DISCUSSION: Various methods of ankle arthrodesis are retrograde intramedullary nails, screws, and plates. In this report, we opt for plate fixation because it allows for stable internal fixation, adequate compression, high angular stability, and a lower irreversible deformation in osteoporotic bone. CONCLUSION: Double posterior lateral plating ankle arthrodesis provided satisfactory clinical and radiological outcomes. This method can be an alternative for patients with Charcot ankle requiring ankle arthrodesis.

Validity and Reliability of the Indonesian Version of the Kujala Score for Patients With Patellofemoral Pain Syndrome.

BACKGROUND: The Kujala score is a useful diagnostic tool to evaluate patellofemoral pain syndrome (PFPS). However, no validated Indonesian version of the Kujala score has been available. PURPOSE: To develop and validate an Indonesian version of the Kujala score. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: This was a cross-sectional study to develop an Indonesian version of the Kujala score by using a forward-backward translation protocol. The resulting questionnaire was given to 51 patients diagnosed with PFPS. The validity of the questionnaire was evaluated by correlating the final score with the Indonesian version of the 36-Item Short Form Health Survey (SF-36). Reliability was measured by evaluating the internal consistency (Cronbach alpha) and test-retest reliability (intraclass correlation coefficient [ICC]). RESULTS: The Indonesian version of the Kujala score had a positive correlation with the physical components of the SF-36. The internal consistency was fairly high (α = .74), and the test-retest reliability was excellent (ICC, 0.996). CONCLUSION: The Indonesian version of the Kujala score was proven to be a valid and reliable tool to diagnose PFPS. Future epidemiological studies could implement this score to find the prevalence of PFPS in Indonesia. Further, ensuing studies could explore the application of this scoring system in posttreatment and postoperative settings.

Union of Brodsky type 1/Eichenholtz stage III Charcot neuroarthropathy after forefoot arthrodesis.

INTRODUCTION: One of the surgical intervention options for Charcot neuroarthropathy (CN) is arthrodesis. The arthrodesis procedure for the foot and ankle joint have been widely used in previous studies. This study aimed to evaluate the functional and radiological outcomes after arthrodesis procedure for the CN patient with Brodsky type 1/Eichenholtz stage III. PRESENTATION OF CASE: A 49-years-old diabetic woman presented with alteration of her right foot's shape and a cracking sensation while walking in the last six months. Rocker-bottom deformity and a decreased sensation on the right foot were found, and the initial American Orthopaedic Foot & Ankle Society (AOFAS) score was 45. Subsequently, forefoot arthrodesis of the right foot was performed. DISCUSSION: Several studies state that arthrodesis procedure is often used for CN management in order to achieve a plantigrade and stable foot. This study presents an improvement of the foot arch, AOFAS score, and union of the talus six months after surgery. CONCLUSION: The arthrodesis procedure by using screws and Kirschner wire (K-wire) fixation is an effective method in CN management if the patient is compliant. This study showed a good result, anatomically restored the foot arch, and excellent radiological union, but different tools to analyze foot functional status and longer follow up period are needed for a better analysis.

Effect of nickel, cobalt, and iron on methanogenesis from methanol and cometabolic conversion of 1,2-dichloroethene by Methanosarcina barkeri.

Methanogens are responsible for the last step in anaerobic digestion (AD), in which methane (a biofuel) is produced. Some methanogens can cometabolize chlorinated pollutants, contributing for their removal during AD. Methanogenic cofactors involved in cometabolic reductive dechlorination, such as F430 and cobalamin, contain metal ions (nickel, cobalt, iron) in their structure. We hypothesized that the supplementation of trace metals could improve methane production and the cometabolic dechlorination of 1,2-dichloroethene (DCE) by pure cultures of Methanosarcina barkeri. Nickel, cobalt, and iron were added to cultures of M. barkeri growing on methanol and methanol plus DCE. Metal amendment improved DCE dechlorination to vinyl chloride (VC): assays with 20 µM of Fe3+ showed the highest final concentration of VC (5× higher than in controls without Fe3+ ), but also in assays with 5.5 µM of Co2+ and 5 µM of Ni2+ VC formation was improved (3.5-4× higher than in controls without the respective metals). Dosing of metals could be useful to improve anaerobic removal of chlorinated compounds, and more importantly decrease the detrimental effect of DCE on methane production in anaerobic digesters.

Primary single stage Total Hip Arthroplasty in a patient 40 years post traumatic Hip dysplasia, a case report.

INTRODUCTION: Hip dysplasia refers to an abnormal development of size, shape, or organization of the femoral head, acetabulum, or both. Managing acetabular dysplasia is very challenging in arthroplasty especially in traumatic hip dysplasia case. Mostly, hip dysplasia cases need a special implant, procedure and techniques. CASE PRESENTATION: We performed primary Total Hip Arthroplasty (THA) + partial tenotomy of hamstring, iliotibial band, hip abductor in a 73 year old male. His main complaint was that he was unable to sit due to an increasingly intense pain since 3 months ago and he has been unable to walk properly since 40 years ago when he had a major traffic accident and received inadequate treatment. The procedure had been successfully done using a well press-fit cementless acetabular cup and a cementless narrow stem application 1 cm on leg length discrepancy (LLD). CONCLUSION: Preoperative planning, surgical techniques and a post-surgery rehabilitation are the key to a successful management in this case.

Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice.

BACKGROUND: Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice. METHODS: Plasmodium berghei ANKA infection in male ICR mice was used as a model for malaria infection. Modulation of IL-18 release was carried out by treatment of malarial mice with recombinant mouse IL-18 (rmIL-18) and recombinant mouse IL-18 Fc chimera (rmIL-18Fc) intravenously. Histopathological study and analysis were performed on major organs including brain, liver, spleen, lungs and kidney. RESULTS: Treatment with rmIL-18Fc resulted in significant improvements on the histopathological conditions of the organs in malaria-infected mice. CONCLUSION: IL-18 is an important mediator of malaria pathogenesis and targeting IL-18 could prove beneficial in malaria-infected host.

The combination of mitragynine and morphine prevents the development of morphine tolerance in mice.

Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine.

Therapeutic potential of Moringa oleifera extracts against acetaminophen-induced hepatotoxicity in rats.

CONTEXT: Moringa oleifera Lam. (Moringaceae) is a rich source of essential minerals and antioxidants; it has been used in human and animal nutrition. The leaves and flowers are being used by the population with great dietary importance. OBJECTIVE: The present study was to investigate the therapeutic effects of the hydroethanolic extract of Moringa oleifera (MO) leaves and flowers against hepatotoxicity induced by acetaminophen (APAP) in rats. MATERIALS AND METHODS: In the hepatoprotective study, either flowers or leaves of hydroethanolic extract (200 or 400 mg/kg bw through IP injection) were administered an hour after APAP administration. N-Acetylcysteine (NAC) was used as the positive control for this study. Liver and kidney function tests including lipid peroxidation levels were analyzed and histopathological changes of liver and kidney were also observed. RESULTS: Acetaminophen-induced hepatotoxicity increased the activities of liver marker enzymes. Histologically, the liver was observed to have inflammation and bridging necrosis. Liver marker enzymes were significantly reduced when treated with flower and leaf extracts of MO in animals with APAP induced toxicity. In addition, there were no significant changes observed in clinical markers of kidney function. Histological observation on liver tissue from the rats treated with MO flower and leaf extract showed reduction in the severity of the liver damage. DISCUSSION AND CONCLUSION: These results indicated the possible therapeutic action of flower and leaf extract from MO in protecting liver damage in rats given an over dosage of APAP.

Antinociceptive action of isolated mitragynine from Mitragyna Speciosa through activation of opioid receptor system.

Cannabinoids and opioids systems share numerous pharmacological properties and antinociception is one of them. Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system. In the present study, the action of MG was investigated as the antinociceptive agent acting on Cannabinoid receptor type 1 (CB1) and effects on the opioids receptor. The latency time was recorded until the mice showed pain responses such as shaking, licking or jumping and the duration of latency was measured for 2 h at every 15 min interval by hot plate analysis. To investigate the beneficial effects of MG as antinociceptive agent, it was administered intraperitoneally 15 min prior to pain induction with a single dosage (3, 10, 15, 30, and 35 mg/kg b.wt). In this investigation, 35 mg/kg of MG showed significant increase in the latency time and this dosage was used in the antagonist receptor study. The treated groups were administered with AM251 (cannabinoid receptor-1 antagonist), naloxone (non-selective opioid antagonist), naltrindole (δ-opioid antagonist) naloxonazine (µ(1)-receptor antagonist) and norbinaltorpimine (κ-opioid antagonist) respectively, prior to administration of MG (35 mg/kg). The results showed that the antinociceptive effect of MG was not antagonized by AM251; naloxone and naltrindole were effectively blocked; and norbinaltorpimine partially blocked the antinociceptive effect of MG. Naloxonazine did inhibit the effect of MG, but it was not statistically significant. These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.