Preservation Of Function Research Articles

Preservation of coagulation function by normothermic machine perfusion in liver transplant as evidenced by thromboelastography parameters

The use of normothermic machine perfusion over static cold storage in liver transplantation has been shown to reduce post-transplant risks of early allograft dysfunction, primary nonfunction, and ischemic cholangiopathy, and its increasing use has played a role in the expanded utilization of marginal livers. While studies have demonstrated improved clinical outcomes utilizing normothermic machine perfusion over static cold storage preservation, real-time intraoperative data reflecting the quality and viability of normothermic machine perfusion livers is limited. This retrospective, single-center study compared normothermic machine perfusion vs static cold storage livers in first-time liver transplant recipients through the evaluation of synthetic coagulation function as measured by thromboelastography and conventional coagulation testing. Secondarily, transfusion utilization between the two cohorts were reviewed. 186 liver transplant recipients receiving allografts from donors after circulatory death were included in the study, of which 99 (53%) allografts were preserved in static cold storage, and 87 (47%) allografts were placed on the TransMedics Organ Care System. Study findings showed normothermic machine perfusion livers supported with the TransMedics Organ Care System were associated with increased synthetic coagulation function and less excess fibrinolysis in the post-reperfusion period compared to static cold storage livers, and that these findings were better reflected in real-time with thromboelastography monitoring vs conventional coagulation testing. Following reperfusion, there was a significant decrease in the transfusion of blood products in the normothermic machine perfusion group compared with that in the static cold storage group. Overall, we determined that the use of intraoperative thromboelastography can provide real-time data to assess one aspect of reperfusion liver quality and viability.

Reconstructive Techniques Following Malignant Eyelid Tumour Excision-Our Experience.

Background: Malignant eyelid tumours present a considerable challenge in the field of ophthalmic oncology, necessitating a combination of precision oncological care and meticulous reconstruction to ensure the preservation of eyelid functionality and the maintenance of facial aesthetics. Method: This study presents a review of the outcomes of 167 patients who underwent eyelid reconstruction following the excision of primary non-melanocytic malignant tumours. The choice of reconstruction technique was dependent on a number of factors, including the stage of the tumour, its location, and the characteristics of the patient. The most commonly used techniques included regional flaps, local flaps, and skin grafts. The most frequently employed reconstruction techniques were forehead flaps (59 cases), simple excisions (38 cases), and Mustarde cheek flaps (16 cases). Result: The postoperative complications, including ectropion, epiphora, and flap necrosis, were recorded. However, no significant correlation was found between the risk of complications and either the location of the tumour or the reconstruction method employed. Despite the complexity of medial canthal and lower eyelid reconstruction, satisfactory aesthetic and functional outcomes were generally achieved. Conclusions: This study emphasises the importance of individualised surgical planning, highlighting the advantages and limitations of various techniques to optimise both the functional and aesthetic results.

Modified infra-promontorium trans-channel approach to the petrous apex. Case report

This article describes the approach to the petrous pyramid developed at National Medical Research Center of Otorhinolaryngology, namely an endoscopy – microscopy-guided modified trans-channel infra-promontorium approach with internal carotid artery retraction maneuver in patients with lesions of the petrous pyramid but with preserved hearing. A clinical report describing the apical cholesteatoma of the petrous pyramid and the use of this approach are presented. Anatomical and functional features after the surgery are also described. The purpose of this paper is advancing of the surgical approach to the petrous pyramid with the possibility of hearing preservation. The results of surgical treatment in lesions of the petrous pyramid were evaluated in the immediate and distant periods. The functions of facial mimic muscles were evaluated immediately after the surgery, in 6 months, and in one year. The functions of facial mimic muscles remained at the baseline level during the whole follow-up period. The pure tone audiogram demonstrated the preserved hearing function in the postoperative period. Complete elimination of the pathological process was achieved in all cases (n=15); according to the MRI of the temporal bones, no relapses occurred in a year. The surgical approach proposed for patients with the lesions of the petrous pyramid enables complete removal of the pathological process from the petrous pyramid with the preservation of hearing and facial functions, based on the subjective examinations (audiometry, facial function diagnosis) and radiology (CT and MRI of temporal bones) at the preoperative stage.

Translation Strategies of English Passive Constructions into Arabic: An Analysis of Google Translation Engine Produced Translations Using House’s TQA Model

This study explores the translation of English passive constructions into Arabic, focusing on the prevalent translation shifts and the preservation of the source functions within this process. Utilizing a qualitative methodology, it analyzes passive constructions from an English economic-political article based on House’s (2015) Translation Quality Assessment model. It reviews all passive participles classifying them into verbal and adjectival ones. The research aims to understand how these translation shifts cater to the syntactic and semantic needs of the Arabic language, particularly how machine translation tools like Google Translation engine handle these transformations. Data collected include various English passive constructions and their Arabic translations, providing a foundation for assessing either their adherence to the target language’s norms and preferences or to the literal approach that may lead to affect such preferences and norms. Key findings reveal how Google Translation engine tends to translate according to Arabic norms and produce a natural translation while preserving the source functions. The five translation strategies used by Google Translate when translating passive constructions from English to Arabic in economic-political texts are: 1) adjectival phrases, 2) active structures, 3) passive structures with internal vowel changes, 4) verbless structures with verbal nouns, and 5) verbal phrases with 'tamma'. However, the influence of such an approach may lead to manipulating the source function, which may lead to misunderstandings or to unbalanced power relations.

Optimizing the Preoperative Preparation of Sarcopenic Older People: The Role of Prehabilitation and Nutritional Supplementation before Knee Arthroplasty.

Age-related loss of skeletal muscle strength and mass is linked to adverse postoperative outcomes in older individuals with sarcopenia. Half of patients suffer from severe associated osteoarthritis requiring orthopedic interventions. Mitigating the onset and progression of sarcopenia before surgery is essential to improve the prognosis and reduce surgical complications. The aim of this research was to innovatively explore whether the preoperative period could be the appropriate timeframe to empower surgical resilience, through prehabilitation and dietary supplementation, in older sarcopenic patients undergoing knee arthroplasty. The current literature concerning the effectiveness of prehabilitation and dietary supplementation before knee arthroplasty in sarcopenic older individuals was reviewed, following the SANRA criteria, between December 2023 and February 2024. The study inclusion criteria were as follows: (1) prehabilitation and/or dietary supplementation interventions; (2) human participants aged 65 years and older; (3) relevant outcome reporting (functional status, postoperative complications, and patient-reported outcomes); and (4) articles written in English The extracted information included study characteristics, demographics, intervention details, outcomes, and the main findings. Merged prehabilitation and dietary supplementation strategies extrapolated from the current literature and involving strength, resistance, balance, and flexibility training, as well as essential amino acids, iron, vitamin D, adenosine triphosphate, and glucosamine sulphate supplementation, could improve the functional capacity, ability to withstand the upcoming surgical stressors, and postoperative outcomes in older people undergoing knee arthroplasty. Addressing complex links between knee osteoarthritis and sarcopenia in older individuals undergoing knee arthroplasty requires a multidimensional approach. Prehabilitation emerges as a crucial preliminary step, allowing the optimization of surgical outcomes. Nutraceutical integration, included in a comprehensive care plan, could have a synergic effect in achieving prehabilitation goals. Those interventions are essential for surgical resilience, in terms of muscle function preservation, recovery acceleration, and overall quality of life enhancement. Intensive collaboration among specialists could advance knowledge and the sharable consensus concerning the critical and evolutive field of perioperative care.

The effect of Amantadine on recovery, postoperative cognitive dysfunction and pain after propofol anesthesia in mice

IntroductionPostoperative cognitive dysfunction (POCD) encompasses a spectrum of cognitive impairments following surgery, attributed to disruptions in brain homeostasis. The pathogenesis involves glutamate toxicity, GABA receptor dysfunction, and alterations in NMDA and AMPA receptors. This study aimed to investigate the impact of pre-anesthetic amantadine administration on postoperative recovery time, POCD, and stress-related pain levels when combined with propofol anesthesia. MethodsTwenty-four adult male BALB/C mice were divided into four groups: Control, Propofol, Amantadine, and Amantadine+Propofol. Amantadine and propofol doses were administered intraperitoneally based on previous literature. Recovery time, pain levels (assessed via tail pinch and hot plate tests), cognitive functions (evaluated through Morris Water Maze), and locomotor activity (measured via Open Field Test) were recorded. ResultsAmantadine administration significantly reduced recovery time from propofol anesthesia, prolonged pain perception, and preserved cognitive functions compared to propofol alone. The time spent in the target quadrant in the Morris Water Maze was significantly longer in groups receiving amantadine. Additionally, the distance covered until finding the platform was significantly shorter in the propofol-only group. DiscussionAmantadine's neuroprotective effects, attributed to its antagonistic action on glutamate and NMDA receptors, mitigate the detrimental effects of propofol on cognitive function and pain perception. This study highlights the potential of combining amantadine with propofol to enhance postoperative outcomes. ConclusionAmantadine administration before propofol anesthesia positively influenced postoperative recovery, cognitive function preservation, and stress-related pain perception in mice. These findings suggest a potential therapeutic strategy to mitigate POCD and pain associated with surgery.

Impact of the Preservation of Residual Kidney Function on Hemodialysis Survival: Results from the BISTRO Trial.

Preservation of residual kidney function (RKF) in dialysis patients has been associated with improved survival. RKF in the BISTRO trial was relatively well preserved and here we describe its association with survival during the trial and extended follow-up. RKF, measured as the average urea and creatinine clearance (GFR) or 24-hour urine volume was assessed at baseline, one, two and three months and three-monthly up to 2 years in incident haemodialysis patients. Time to event survival data or competing events (transplantation, modality change) were obtained for 50 months post enrolment via data linkage with the UK Renal Registry. Cox proportional hazards regression survival models, including those incorporating change in GFR from baseline as a time-varying variable and joint regression models for longitudinal and survival data (longitudinal models for GFR or urine volume) were used to explore the relationship of RKF preservation with survival. Analyses were adjusted for age, sex, comorbidity and ethnicity. 2919 measures of RKF were made in 387 patients from 32 UK dialysis units. Higher age and comorbidity score associated with increased mortality in all models. Baseline GFR reduced the risk of death (Hazard Ratio: 0.918 95%CI: 0.844, 0.999) per ml/min/1.73m2. A greater fall in GFR and urine volume from baseline was associated with a non-significant increased risk of death as visualised on spline plots. In the joint survival models higher GFR (adjusted HR: 0.88 95%CI 0.80, 0.97) or urine volume (adjusted HR: 0.75 95%CI 0.57, 0.95 per L) at any time point associated with better survival. Lower RKF during the first two years of haemodialysis is associated with an increased death risk for up to 50 months following dialysis initiation. This adds to a growing body of evidence that interventions to preserve RKF should be developed and tested in clinical trials.

Proximal Tubule Secretory Clearance, Injury, and Kidney Viability in Cirrhosis.

Cirrhosis affects all structures of the kidney, in particular the tubules which are responsible for secretion of protein-bound metabolites and electrolyte/water homeostasis. Yet, prevailing assessments of kidney function focus solely on glomerular filtration rate (GFR) which may incompletely reflect these processes. We sought to characterize markers of tubular function, injury, and viability in patients with and without cirrhosis. We recruited outpatients undergoing liver transplantation evaluation for a collection of plasma and 24-hour urine, matching by GFR to control participants without cirrhosis. We measured urinary kidney injury molecule-1 (KIM-1), a marker of proximal tubular injury, as well as epidermal growth factor (EGF), a marker of viability necessary for tubular epithelial cell proliferation after injury. We also estimated secretory clearance by measuring several highly secreted endogenous metabolites in urine and plasma. We recruited 39 patients with cirrhosis (mean MELD-Na 17±4, Child-Pugh 8±2, eGFR 66±20 ml/min/1.73m2) and 58 GFR-matched controls without cirrhosis (eGFR 66±21 ml/min/1.73m2). Urinary KIM-1 was 4.4-fold higher than controls (95% CI:2.9-6.5), and EGF averaged 7.41-fold higher than controls (95% CI:2.15-25.53). We found that of 8 solutes, 5 had significantly greater kidney clearance in cirrhosis (1.3-2.1-fold higher): indoxyl sulfate, p-cresol sulfate, pyridoxic acid, tiglylglycine, and xanthosine. Cirrhosis was characterized by molecular signs of tubular injury in stable outpatients without acute kidney injury, accompanied by largely preserved tubular secretory clearance and greater signs of tubular viability. Within the limitations of the study, this suggests a phenotype of chronic ischemic injury but with initial preservation of tubular function in cirrhosis.

7770 Damage of Ovarian Vasculature by Chemotherapies induces Ovarian Dysfunction in Mice

Abstract Disclosure: W. So: None. R. Dong: None. Y. Luan: None. A. Abazarikia: None. S. Kim: None. Background: Chemotherapy demonstrates efficacy to destroying cancer cells; however, it can inadvertently impact normal healthy cells, leading to irreversible side effects, particularly affecting the ovaries in female patients. Female cancer survivors encounter endocrine dysfunction and infertility due to ovarian damage caused by gonadotoxic cancer therapies. The ovary, a vital organ responsible for producing oocytes and endocrine hormones, faces significant challenges following such treatment. A study with premenopausal breast cancer patients reported a significant reduction in ovarian blood flow and volume immediately following chemotherapy. The preservation of ovarian function depends on the ovarian vasculature in supporting the development and maintenance of ovarian follicles. Despite its importance, the relationship between ovarian vasculature and follicle following chemotherapy has not been studied. Results: To investigate the direct impacts of chemotherapy, ovaries from postnatal 5 CD-1 mice were subjected to testing with three chemotherapeutic agents: cisplatin (CDDP), cyclophosphamide (CPA), and doxorubicin (DOXO). The expression of CD31/PECAM-1 (platelet endothelial adhesion molecule) exhibited a significant decrase after 96 hours of culture with 4-HC, an active metabolite of CPA. This reduction implies that ovarian vasculature was also compromised when chemotherapy eliminated immature follicles. In order to evaluate the influence of vascular endothelial growth factor (VEGF) in safeguarding both vasculature and ovarian follicles, ovaries were co-cultured with VEGF165 or VEGF165b in combination with chemotherapy. Interestingly, pre-treatment with VEGF165 before 4-HC led to an increased expression of CD31 in the cortex area, while VEGF165b further diminished CD31 expression compared to treatment with 4-HC alone. Additionally, adolescent CD-1 mice were intraperitoneally injected with CDDP, CPA, or DOXO, and ovaries were harvested one week after injection. Ovaries treated with chemotherapeutic agents exhibited a reduction in ovary weight and decreased CD31 expression compared to control mice. Conclusions: We propose that these chemotherapeutic agents not only induced the loss of ovarian follicles but also affected ovarian vasculature in mice. This suggests a potential decrease in folliculogenesis within the ovary, coupled with the depletion of ovarian reserve, as the delivery of nutrients and oxygen to growing ovarian follicles may be compromised. VEGF165 may play a beneficial role in maintaining ovarian function by safeguarding ovarian vasculature following chemotherapy. Understanding these intricate dynamics is essential for developing strategies to mitigate the negative impact of cancer therapies on reproductive health in female cancer survivors, particularly in preserving endocrine function and reproductive lifespan. Presentation: 6/2/2024

Interstitial brachytherapy for periocular nonmelanoma skin cancers: Impact on organ and function preservation

PurposeTo study the local control, toxicity, organ and functional preservation and cosmetic outcomes after interstitial brachytherapy for periocular nonmelanoma skin cancers. Methods and MaterialsPatients with skin cancers of upper and lower eyelid, medial and lateral canthus and the infra-orbital region treated with high dose rate (HDR) interstitial brachytherapy (ISBT) using 192-Iridium (192Ir) between December 2010 and July 2022 were included and data collected from a prospectively maintained database. Local control, survival outcomes, acute and late RTOG toxicity, functional and cosmetic outcomes were analysed. ResultsSixteen patients were included. Nine patients had lower eyelid tumors, 5 patients had tumors in canthi and two patients had skin tumor in the infra-orbital region. The median dose for definitive ISBT was 49 Gy in 14 fractions. After a median follow up of 73 months, all patients treated with definitive and adjuvant ISBT were locally controlled. Three of the four patients who received salvage ISBT for post-surgical failure had local recurrences and all were effectively managed with salvage re-surgery. Of the two deaths, none were disease related. Organ and function preservation was achieved in 15 (93.7 %) and 13 (81.2 %), respectively, with one patient being lost to follow up. Excellent, good, fair and poor cosmesis was seen in 6 (40 %) patients, 6 (40 %) patients, 2 (14 %) patients and 1(6 %) patient, respectively. ConclusionHDR-ISBT was safe and effective for skin tumors around the eye and resulted in excellent local control and survival outcomes preserving organ and function in majority of patients with good-excellent cosmesis.

Dexrazoxane prevents vascular toxicity in doxorubicin-treated mice

BackgroundDoxorubicin (DOX) is used for breast cancer and lymphoma, but can cause cardiotoxicity, arterial stiffness, and endothelial dysfunction. We recently reported SERPINA3N as biomarker of cardiovascular toxicity in patients and mice. Dexrazoxane (DEXRA) is an FDA-approved drug that prevents DOX-induced cardiac toxicity in high-risk patients. However, the effect of DEXRA on vascular dysfunction during DOX treatment has not been documented. Therefore, here we investigated whether DEXRA protects against DOX-induced arterial stiffness, endothelial dysfunction, and SERPINA3N upregulation in tissue and plasma from mice.MethodsMale C57BL6/J mice were treated with DOX (4 mg/kg), DEXRA (40 mg/kg), a combination (DEXRA + DOX), or VEHICLE (0.9% NaCl) weekly i.p. for 6 weeks (n = 8 per group). Cardiovascular function was measured in vivo by ultrasound imaging at baseline, weeks 2 and 6. Vascular reactivity was analyzed ex vivo in the thoracic aorta at week 6 and molecular analysis was performed.ResultsDEXRA prevented left ventricular ejection fraction decline by DOX (DEXRA + DOX: 62 ± 2% vs DOX: 51 ± 2%). Moreover, DEXRA prevented the increase in pulse wave velocity by DOX (DEXRA + DOX: 2.1 ± 0.2 m/s vs DOX: 4.5 ± 0.3 m/s) and preserved endothelium-dependent relaxation (DEXRA + DOX: 82 ± 3% vs DOX: 62 ± 3%). In contrast to DOX-treated mice, SERPINA3N did not increase in the DEXRA + DOX group.ConclusionOur results not only confirm the cardioprotective effects of DEXRA against DOX-induced cardiotoxicity but also add preservation of vascular endothelial cell function as an important mechanism. Moreover, the study demonstrates the potential of SERPINA3N as a biomarker for monitoring cardiovascular complications of DOX in high-risk patients.

Endoscopic En Bloc Resection of Giant Cell Tumor of Tendon Sheath of Anterior Ankle

Giant cell tumor of the tendon sheath (GCTTS) originates from the synovial cells of the tendon sheath. It is one of the most common benign soft-tissue tumors of the foot and ankle affecting the joints, bursae, and tendon sheaths and can behave in a locally aggressive manner. Complete surgical resection with long-term follow-up is the preferred treatment. Because GCTTS is a benign condition, the equilibrium between the quality of the surgical margins and functional preservation should be considered. If more aggressive resection is applied, the outcome may negatively affect quality of life, whereas incomplete resection may lead to recurrence. The purpose of this technical note is to describe the details of endoscopic en bloc resection of GCTTS of the anterior ankle. This endoscopic approach can provide a magnified view of the operative site, allowing accurate surgical assessment to ensure complete resection of the lesion without damage to the adjacent normal structures.

Photodynamic Therapy for Oral Squamous Cell Carcinoma: Current Status, Challenges, and Prospects.

Oral squamous cell carcinoma (OSCC) is the most prevalent and deadly malignancy of the head and neck. The standard treatments for OSCC are surgery, radiotherapy, and chemoradiotherapy, which can cause severe cosmetic and functional damage to the oral cavity and impair the patients' quality of life. Photodynamic therapy (PDT) is a promising alternative that uses light-activated photosensitizers to induce selective phototoxicity and necrosis in the target tissues. PDT has several advantages over conventional treatments, such as minimal invasion, low side effects, high selectivity and preservation of the oral function and appearance. This review explores the principles, mechanisms, and current applications of PDT for OSCC. We address the challenges, such as the depth of light penetration and tissue hypoxia, and underscore the progressive innovations in photosensitizer enhancement, nanotechnological integration, and precision therapy. The exploration of biomarkers for refining patient selection and tailoring individualized treatment regimens is also undertaken. PDT holds promise as a secure and efficacious modality for OSCC management. Nonetheless, additional investigation is imperative to refine treatment protocols and validate sustained therapeutic success.

Meta-analysis of clinical outcomes of robot-assisted partial nephrectomy and classical open partial nephrectomy.

Robotic-assisted partial nephrectomy (RAPN) has emerged as a promising alternative to classical partial nephrectomy (CPN). This study aimed to compare the outcomes of RAPN and CPN for treating localized renal tumors through a meta-analysis of available literature. Chinese databases, such as CNKI, Chinese Science and Technology Periodicals Database (VIP), and Wanfang Full-text Database, were searched using Chinese search terms, and all published articles on PubMed and Web of Science were searched using English search terms. Articles on Localized Renal Tumors were included. RevMan5.3 software was used for meta-analysis. The funnel plots were drawn using Stata software to assess publication bias. This study aimed to identify the differences between robotic-assisted partial nephrectomy and classic partial nephrectomy in patients with localized renal tumors. In total, 67 articles with 17677 patients were included. The results demonstrate the advantages of RAPN over CPN for localized renal tumors. Compared to CPN and RAPN had significant differences in intraoperative blood loss, hospital stay duration, incidence of perioperative complications, and proportion of patients requiring blood transfusion. Regarding surgical outcomes, RAPN showed more favorable results regarding the incidence of positive resection margins, postoperative decline in glomerular filtration rate (GFR), postoperative local recurrence rate, and proportion of Trifecta achieved. However, there was no significant difference between RAPN and CPN regarding 5-year tumor-specific survival rates. The study suggests that robotic-assisted partial nephrectomy is a viable alternative to classic surgery for renal tumors. The strengths of this study are the use of a comprehensive search strategy and the inclusion of studies published in both English and Chinese. The limitations of this study are the small sample size and the need for long-term follow-up data. RAPN and CPN have similar overall survival outcomes for treating localized renal tumors. However, RAPN may offer advantages in terms of perioperative outcomes and preservation of renal function. Further studies are needed to confirm these findings and to identify the optimal surgical approach for individual patients.

Effect of Expanded Hemodialysis with Theranova Dialyzer on Preservation of Residual Kidney Function in Incident Hemodialysis Patients: THREAD Randomized Controlled Trial

Effect of Expanded Hemodialysis with Theranova Dialyzer on Preservation of Residual Kidney Function in Incident Hemodialysis Patients: THREAD Randomized Controlled Trial

Initial adjustments in the dosage and rest period of gemcitabine plus cisplatin therapy for patients with incurable biliary tract cancer based on baseline estimated glomerular filtration rate (eGFR) values may be crucial for treatment outcomes and the preservation of renal function

Initial adjustments in the dosage and rest period of gemcitabine plus cisplatin therapy for patients with incurable biliary tract cancer based on baseline estimated glomerular filtration rate (eGFR) values may be crucial for treatment outcomes and the preservation of renal function

Targeting PAR2-mediated inflammation in osteoarthritis: a comprehensive in vitro evaluation of oleocanthal’s potential as a functional food intervention for chondrocyte protection and anti-inflammatory effects

BackgroundOsteoarthritis (OA) is a prevalent degenerative joint disease characterized by chronic inflammation and progressive cartilage degradation, ultimately leading to joint dysfunction and disability. Oleocanthal (OC), a bioactive phenolic compound derived from extra virgin olive oil, has garnered significant attention due to its potent anti-inflammatory properties, which are comparable to those of non-steroidal anti-inflammatory drugs (NSAIDs). This study pioneers the investigation into the effects of OC on the Protease-Activated Receptor-2 (PAR-2) mediated inflammatory pathway in OA, aiming to validate its efficacy as a functional food-based therapeutic intervention.MethodsTo simulate cartilage tissue in vitro, human bone marrow-derived mesenchymal stem cells (BMSCs) were differentiated into chondrocytes. An inflammatory OA-like environment was induced in these chondrocytes using lipopolysaccharide (LPS) to mimic the pathological conditions of OA. The therapeutic effects of OC were evaluated by treating these inflamed chondrocytes with various concentrations of OC. The study focused on assessing key inflammatory markers, catabolic enzymes, and mitochondrial function to elucidate the protective mechanisms of OC. Mitochondrial function, specifically mitochondrial membrane potential (ΔΨm), was assessed using Rhodamine 123 staining, a fluorescent dye that selectively accumulates in active mitochondria. The integrity of ΔΨm serves as an indicator of mitochondrial and bioenergetic function. Additionally, Western blotting was employed to analyze protein expression levels, while real-time polymerase chain reaction (RT-PCR) was used to quantify gene expression of inflammatory cytokines and catabolic enzymes. Flow cytometry was utilized to measure cell viability and apoptosis, providing a comprehensive evaluation of OC’s therapeutic effects on chondrocytes.ResultsThe results demonstrated that OC significantly downregulated PAR-2 expression in a dose-dependent manner, leading to a substantial reduction in pro-inflammatory cytokines, including TNF-α, IL-1β, and MCP-1. Furthermore, OC attenuated the expression of catabolic markers such as SOX4 and ADAMTS5, which are critically involved in cartilage matrix degradation. Importantly, OC was found to preserve mitochondrial membrane potential (ΔΨm) in chondrocytes subjected to inflammatory stress, as evidenced by Rhodamine 123 staining, indicating a protective effect on cellular bioenergetics. Additionally, OC modulated the Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL)/Receptor Activator of Nuclear Factor Kappa-Β (RANK) pathway, suggesting a broader therapeutic action against the multifactorial pathogenesis of OA.ConclusionsThis study is the first to elucidate the modulatory effects of OC on the PAR-2 mediated inflammatory pathway in OA, revealing its potential as a multifaceted therapeutic agent that not only mitigates inflammation but also protects cartilage integrity. The preservation of mitochondrial function and modulation of the RANKL/RANK pathway further underscores OC’s comprehensive therapeutic potential in counteracting the complex pathogenesis of OA. These findings position OC as a promising candidate for integration into nutritional interventions aimed at managing OA. However, further research is warranted to fully explore OC’s therapeutic potential across different stages of OA and its long-term effects in musculoskeletal disorders.

Characteristics, treatment, and outcomes of spontaneous renal artery dissection: a 10-year retrospective single-center experience.

Spontaneous renal artery dissection (SRAD) is a rare cause of renal failure and renovascular hypertension, with the diagnosis often being delayed and treatment varying across different centers. The objective of this retrospective cohort study was to scrutinize the characteristics, treatment modalities, and outcomes of patients with SRAD at our center over the past ten years. Furthermore, the study sought to identify the most suitable treatment options for different categories of patients with SRAD. Data from 21 consecutive patients who presented with symptoms of SRAD from December 2013 to December 2023 were collected. Lesion characteristics, treatment options, blood pressure (BP) control, serum creatinine and estimated glomerular filtration rate (eGFR) were analyzed. A paired t-test was used for comparisons of BP, serum creatinine, and eGFR. An independent samples t-test was used to analyze baseline BP and BP change in different treatment groups. The mean age, weight, and height of patients with SRAD was 49.2±13.0 (range, 18-69) years, 69.0±9.7 (range, 50-80) kg, and 1.7±0.1 (range 1.6-1.8) m, respectively. New-onset hypertension was found in 8 (38.1%) patients. Renal artery dissecting aneurysm and renal artery stenosis were found in 1 (4.8%) and 4 (19.0%) patients, respectively. Supportive medical treatment alone, endovascular intervention, and nephrectomy were required in 15, 4 and 2 cases, respectively. Stable renal function and satisfactory hypertension control were obtained in all treatment groups, with a median follow-up of 18.1 (range, 12-32) months. Medical management is a reasonable choice in most patients with SRAD. Interventional management is an efficacious strategy for the management of renovascular hypertension and the preservation of renal function.

Cardiac Evaluation in Children With Chronic Renal Failure and Effect of Kidney Transplant.

Cardiovascular diseases are an important cause of mortality and morbidity in children with chronic renal failure. Cardiac evaluation and followup are crucial for these patients before and after renal transplant. Echocardiography is a noninvasive imaging modality that allows for the assessment of cardiac structure and function. We retrospectively investigated pretransplant and posttransplant echocardiography findings for 55 pediatric patients who had underwent kidney transplant. We recorded patient characteristics before and after transplant, including age, sex, follow-up period, etiology of renal failure, left ventricular systolic and diastolic diameters and the associated z scores, left ventricular mass indexes and z scores, ejection fraction and fractional shortening, aortic valve and atrioventricular valve insufficiencies, presence of pulmonary hypertension, and pericardial effusion (if any) in echocardiography. All participants underwent echocardiography at baseline and after 6 months following the transplant procedure. Posttransplant echocardiography evaluations showed that the z scores of left ventricular systolic and diastolic diameters decreased significantly, mitral regurgitation decreased, and left ventricular systolic functions and left ventricular mass index increased. Our study revealed that kidney transplant has a beneficial effect on the cardiovascular status of patients with end-stage renal disease, as shown by improvements in both structural and functional echocardiographic features. Cardiac functions must be monitored regularly before and after transplant. Transplantation is the optimal treatment option for preservation and improvement of cardiovascular functions.

ReCLAIM-2: A Randomized Phase 2 Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation

ObjectiveThis study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with non-central geographic atrophy (GA). DesignReCLAIM-2 was a prospective, phase 2, randomized, placebo-controlled, double-masked, multicenter trial (NCT03891875). SubjectsPatients aged ≥55 years with at least one eye with dry AMD with GA were enrolled. MethodsAdministration of daily subcutaneous elamipretide 40 mg was investigated in subjects for 48 weeks followed by a 4-week follow-up period. Main Outcome MeasuresThe primary efficacy endpoints were the mean change from baseline in low-luminance best-corrected visual acuity (LL BCVA) and the change in square root converted GA area from baseline as measured by optical coherence tomography (OCT). Additional predefined endpoints included ellipsoid zone (EZ) integrity preservation assessment and categorical changes in LL BCVA. The primary safety endpoint was the incidence and severity of adverse events. ResultsOf the 176 patients randomized, there were 117 and 59 patients in the elamipretide and placebo groups, respectively. Although elamipretide did not meet statistical significance for the primary endpoints (mean change in LL BCVA and mean change in square root converted GA area), elamipretide produced a 43% reduction in the mean progression from baseline in the macular percentage of total EZ attenuation/loss (i.e., complete loss of EZ band; nominal P=0.003) and 47% reduction in the mean progression of macular percentage of partial EZ attenuation/degradation (i.e., EZ-RPE thickness of 20 microns or less; nominal P=0.004) versus placebo at week 48. Elamipretide treatment was also associated with significantly more patients experiencing a ≥10 letter gain in LL-BCVA versus placebo (14.6% vs 2.1%; nominal P=0.0404). Adverse events were reported in 86% of those receiving elamipretide and 71% of the placebo group with the most common events being injection site reactions (e.g., pruritus, injection site pain, bruising, erythema). ConclusionsWhile the primary endpoints were not met in this phase 2 study, elamipretide treatment was associated with a slowing of progressive EZ degradation/loss, a surrogate for photoreceptor damage. These findings have important clinical relevance since EZ attenuation/photoreceptor loss precedes and predicts the progressive pathological changes associated with vision loss and AMD. The EZ attenuation/loss endpoint will serve as the regulatory-approved primary endpoint in the elamipretide Phase 3 clinical development program.