Tissue Loss Research Articles

Association Between Wound Healing and the Japanese Below-the-Knee Chronic Total Occlusion Score in Patients With Chronic Limb-Threatening Ischemia After Endovascular Therapy

Introduction: In the current study, we hypothesized that the Japanese below-the-knee chronic total occlusion score could be used to stratify the lesion difficulty of endovascular therapy for below-the-knee chronic total occlusion through angiographic evaluation. We thus aimed to evaluate the prognostic impact of the Japanese below-the-knee chronic total occlusion score in patients with chronic limb-threatening ischemia after successful endovascular therapy for below-the-knee chronic total occlusion. Methods: This was a retrospective, single-center observational study. We enrolled 139 consecutive patients with chronic limb-threatening ischemia (149 limbs), who underwent successful endovascular therapy for chronic total occlusion between February 2008 and December 2017. The Japanese below-the-knee chronic total occlusion score was assessed based on the definition of the target arterial path. The evaluation items were the rate of amputation-free survival and wound healing at 1 year, and the association between wound healing at 1 year and the Japanese below-the-knee chronic total occlusion score. Results: The rates of amputation-free survival and wound healing at 1 year were 88.0 and 56.4%, respectively. Multivariate Cox proportional hazard analysis identified direct flow to the wound (hazard ratio: 2.34, 95% confidence interval: 1.28-4.66; p<0.01); Wound, Ischemia, and foot Infection stages 1-3 (hazard ratio: 2.81, 95% confidence interval: 1.63-5.18; p<0.01); and a Japanese below-the-knee chronic total occlusion score ≤1 (hazard ratio: 1.70, 95% confidence interval: 1.02-2.98; p=0.04) to be predictors of wound healing. Conclusions: A Japanese below-the-knee chronic total occlusion score ≤1, direct flow to the wound, and Wound, Ischemia, and foot Infection stages 1-3 were found to be associated with wound healing after successful endovascular therapy for below-the-knee chronic total occlusion in patients with chronic limb-threatening ischemia. Clinical Impact This study was conducted to evaluate the prognostic impact of the Japanese below-the-knee chronic total occlusion (J-BTK CTO) score in patients with chronic limb-threatening ischemia (CLTI) after successful endovascular treatment (EVT). The results showed that the J-BTK CTO score not only evaluates the difficulty of EVT but also can predict limb prognosis. Using the J-BTK CTO score, it seems possible to predict the limb prognosis and make it useful in clinical practice.

Otoplasty and Ear Reconstruction Complications

AbstractProminauris, often known as prominent ears, is one of the most frequent congenital deformities of the head and neck. Therefore, otoplasty has gained significant popularity and is now one of the most performed procedures in the field of facial plastic surgery.Reconstructing and correcting ear abnormalities remains a challenging procedure in facial plastic and reconstructive surgery. These deformities, whether congenital or acquired, have a substantial influence on patients' lives and inflict psychological harm. Addressing the deformity and tissue loss will improve the overall quality of life.Throughout history, various surgical techniques have been reported for treating external ear abnormalities. While most of these surgeries are considered safe, a comprehensive preoperative evaluation and understanding of the different techniques and risks can minimize potential complications.

Porcine ear necrosis in nursery piglets is preceded by oral manipulations of the ear

Abstract Background Porcine ear necrosis (PEN) is characterized by dry crusts on the ear tip. The crusts often progress to moist and bloody lesions and may lead to partial loss of the ear tissue. The cause and pathophysiology of PEN are unknown. Skin infections, systemic infections, or ear biting have been suggested as a cause of PEN, but no proper evidence has been shown. The behavioural factor has not yet been investigated, therefore this study evaluated the importance of oral manipulations in the occurrence of PEN in nursery pigs. Three farms affected by PEN were visited weekly, and the prevalence and severity were recorded. Video recordings of the animals were performed, and the behaviour was evaluated. The presence of pathogens in the lesions and histological alterations were also analysed. Results The highest percentage of pigs with PEN lesions in the farms ranged between 58 and 93%, with most lesions being of mild to moderate severity. The first ear lesions occurred about 1–2 weeks after an increase in the number of ear manipulations in the pens. The frequency of the ear manipulations clearly changed over time, and the number of oral ear manipulation behaviour significantly differed (P < 0.05) between pigs in pens with high and low PEN prevalence. Increased ear manipulation behaviour was significantly related to a subsequent increase in PEN lesions (OR = 4.3; P < 0.001). Metagenomic investigation of lesion scrapings revealed a variety of pathogens mostly with low abundance, where microscopic alterations were found mainly in the epidermis. Conclusions Oral manipulation of the ear pinnae by pen mates was followed by the development of PEN lesions one to two weeks later. This suggests that the behaviour played an important role in the PEN lesions formation in the nursery pigs of the three farms. Bacteria found in PEN lesions most probably were secondary to initial external skin damage, but their relevance needs to be investigated further.

HPB SO14 - Surprise Inside: Gallbladder Herniation in a Parastomal Hernia - A Rare Case Report and Management Insight

Abstract Background Parastomal hernias are a common complication of stoma formation, affecting approximately 40% of patients within two years. Gallbladder herniation within a parastomal hernia is a rare phenomenon, with only 18 cases previously reported. Patients are typically elderly females, with the condition attributed to ageing factors such as loss of visceral fat and elastic tissue, liver shrinkage, and the increased length and loss of elasticity of the gallbladder mesentery. These factors contribute to visceroptosis of the gallbladder, increasing its mobility and the risk of herniation. Method We present the case of a 68-year-old female with a four-day history of severe parastomal hernia pain and swelling. She had an emergency left hemicolectomy and transverse colostomy in the right upper quadrant 10 years prior for ischaemic colitis and perforation. Her stoma was functioning well. Vital signs and biochemistry results were normal. On examination her hernia was severely tender but partially reducible. CT revealed a right upper abdominal parastomal hernia containing loops of colon and surprisingly the gallbladder with a long stretched cystic duct. There was no evidence of cholecystitis, bowel obstruction, or compromise within the hernial sac. Results With analgesia, the patient's pain improved, though her hernia remained irreducible. She was discharged after two days of conservative management and referred back to the hospital where she had the initial operation. On enquiry with that hospital it was reported that an elective parastomal hernia repair with completion right colectomy and end ileostomy was performed. The gallbladder was mobilised and reduced back into the peritoneal cavity, and the hernial defect was closed. The patient made an excellent recovery and was discharged home three days after surgery. Conclusion Cholecystic parastomal herniation is a very rare phenomenon and should be considered as a differential in similar cases. Management should be based on clinical presentation, radiological diagnosis, and a multidisciplinary team approach. No standardised classification or approach exists. We propose classifying gallbladder herniations as either being simple (without inflammatory sequelae) or complicated (with cholecystitis, gallbladder torsion, incarceration or perforation). Simple herniations, such as the case presented, can be managed electively with intra-operative reduction of the gallbladder sufficing. Complicated herniations during acute admissions indicate the need for emergency surgical intervention with combined cholecystectomy and parastomal hernia repair.

MANEJO DE FERIDAS EM COELHO ATRAVÉS DO USO DA PELE DE TILÁPIA LIOFILIZADA

The study addresses the importance of treating skin lesions in veterinary medicine, with an emphasis on wound healing in rabbits with pododermatitis, including the use of Nile tilapia skin as a therapeutic alternative for grafting after debridement of necrotic ulcers. Skin lesions can be caused by trauma, bites or other causes, compromising vital skin functions, such as protection and defense against infections. Tilapia skin is rich in type I collagen and has been highlighted as an accessible and effective biomaterial in the treatment of wounds, stimulating cell regeneration and healing. The work reports the case of a rabbit, named Paçoca, diagnosed with ulcerative pododermatitis in the left pelvic limb, a chronic condition that can lead to serious complications. The clinical signs of the pathology are pain, abdominal and limb alopecia, edema, ulcerative lesions, loss of joint mobility with the presence of osteolytic reactions. Pododermatitis in rabbits is often related to factors such as cage floor quality, excess weight, and sedentary lifestyle. The rabbit’s treatment included debridement of necrotic tissue and the application of tilapia skin as a graft. The tilapia skin was prepared through a rigorous sterilization and preservation process, involving immersion in specific solutions and the application of antibiotics. The use of this skin as an occlusive dressing helped stimulate growth factors essential for skin regeneration, such as fibroblasts and keratinocytes. The use of this biomaterial proved effective in the treatment of wounds with significant tissue loss, avoiding the need for sutures and promoting healing through the formation of new tissue. Postoperative follow-up included the use of antibiotics and anti-inflammatories, and treatment with tilapia skin contributed to the successful recovery. The study highlights the effectiveness of the biomaterial in the management of skin wounds in rabbits, especially in the recovery of lesions caused by ulcerative pododermatitis. Therefore, after treatment, the rabbit presented good healing, the wound evolved positively, with formation of granulation tissue and epithelialization.

Abstract 4146316: Venous Remodeling and Occlusion Accompany Arterial Pathology in Patients with Chronic Limb Threatening Ischemia

Background: Chronic limb threatening ischemia (CLTI) is defined as the presence of peripheral artery disease (PAD) in combination with rest pain or tissue loss and represents advanced arterial occlusive disease. Little is known about associated venous pathology as prior pathologic reports were limited to evaluation of maximally diseased arterial lesions. Objectives: To characterize arterial and venous histopathology in patients with CLTI. Methods: Tissue containing peripheral arteries and veins from the femoropopliteal to distal tibial arteries was harvested from 10 patients who underwent amputation for CLTI (Fig 1). Vessels were sectioned at 0.5 cm intervals, and histopathologic features were catalogued across 535 arterial and 493 venous sections. Results: Consistent with PAD, atherosclerotic lesions were more prevalent in proximal than distal arteries; 81.8% (27/33) femoropopliteal sections compared to 26.6% (134/502) of tibial sections. Severe stenosis (>90%) was noted in 21.9% (117) of sections and was associated with atherosclerosis (pathological intimal thickening, fibroatheroma, fibrocalcific or fibro-osseous lesions) in 10.3% (12), luminal thrombi in 68.4% (80), or both in 21.4% (25) of arterial sections. In all patients and in 99.0% (488/493) of venous sections, irrespective of the degree of arterial luminal stenosis, adjacent large (≥1000µm) and small diameter veins revealed marked thickening of the vessel wall comprised of fibrosis and smooth muscle hyperplasia (Fig 2). While large veins retained luminal patency, small veins exhibited severe luminal stenosis or obliteration. Venous thrombosis was uncommon, occurring in 3.0% (15/493) of sections. Conclusions: Venous remodeling with stenosis and occlusion is highly prevalent and coincides with arterial disease pathology in patients with CLTI. This novel finding of previously underappreciated and severely altered venous pathology suggests a possible additional mechanism for limb ischemia in CLTI.

Abstract 4146306: Rural Urban Disparities in Inpatient Outcomes of Chronic Limb-Threatening Ischemia in the United States

Background: Chronic limb-threatening ischemia (CLTI) is a severe form of peripheral artery disease characterized by chronic ischemic rest pain, non-healing wounds, or gangrene in one or both legs. With prevalence rates of 1-2% in the United States (increasing with age, with over 20% of adults over 70 diagnosed with CLTI) and 1-year mortality rates approaching 20-25%, CLTI is a critical public health issue due to its significant impact on patient morbidity, mortality, and healthcare resources. Aims: To understand if disparities exist between rural and urban inpatient outcomes for patients with CTLI. Methods: A retrospective analysis of the National Inpatient Sample database from 2016 to 2021 was conducted to identify patients admitted with CLTI according to ICD-10 codes. Patients were stratified by rural and urban status, followed by propensity-matched analysis to compare inpatient outcomes between these groups. Results: A total of 2,667,279 patients with CLTI, with 445255 (16.7%) categorized as rural status and the remaining 83.3% categorized as urban status, were included in this study. Patients belonging to rural status had an increased odds of in-hospital mortality (aOR)=1.35; 95% CI 1.26-1.45; p<0.001), in-patient sudden cardiac arrest (aOR=1.27; 95% CI=1.13-1.43; p<0.001), cerebrovascular accidents (aOR=1.31; 95% CI=1.19-1.45; p<0.001), venous thromboembolism (aOR=1.18; 95% CI=1.09-1.27; p<0.001), surgical site infection (aOR=1.25; 95% CI=1.16-1.35; p<0.001), requirement for vasopressors (aOR=2.02; 95% CI=1.76-2.32; p<0.001), invasive (aOR=1.18; 95% CI=1.10-1.26; p<0.001) and non-invasive (aOR=1.37; 95% CI=1.25-1.50; p<0.001) mechanical ventilation, hemodialysis (aOR=1.11; 95% CI=1.06-1.15; p<0.001), major amputation (aOR=1.38; 95% CI=1.32-1.43; p<0.001), surgical revascularization (aOR=1.53; 95% CI=1.46-1.60; p<0.001), endovascular revascularization (aOR=1.53; 95% CI=1.46-1.60; p<0.001), and blood transfusion (aOR=0.92; 95% CI=0.88-0.97; p=0.001). No difference was observed in the odds of acute myocardial infarction (aOR=1.06; 95% CI=0.99-1.14; p=0.082) and risk of acute kidney injury (aOR=0.99; 95% CI=0.96-1.02; p=0.485). Conclusions: Disparities in CLTI outcomes are evident, with patients from rural areas experiencing worse outcomes than their urban counterparts. Future research should focus on understanding the underlying causes of these disparities and developing targeted interventions to bridge the gap between rural and urban health care outcomes.

Abstract 4130368: Outcomes of Patients with Critical Limb Ischemia and Chronic Kidney Disease: A National Perspective

Background: Studies exploring the relationship between peripheral arterial disease (PAD), critical limb ischemia (CLI), and chronic kidney disease (CKD) and its effect on in-hospital outcomes are limited. Objectives: We aimed to analyze the outcomes of patients with CKD and PAD who are admitted for CLI. Methods: We utilized the National Inpatient Sample (NIS) to capture hospitalizations for CLI from 2016-2020 and then identified cases with concomitant CKD. The primary outcome was mortality, and secondary outcomes were cerebrovascular accident, major bleeding, vasopressor requirement, percutaneous coronary intervention, cardiac arrest, acute respiratory failure, transfusion, length of stay (LOS), and total hospital charges. Multivariable logistic regression was performed to adjust for covariates. Results: A total of 441,245 patients with CLI were identified, of which 122,370 (27.7%) reported concomitant CKD. Patients with CKD had a higher in-patient mortality (OR 1.68, CI, 1.17-1.68, p < 0.001), vascular complications (OR 1.31, 95% CI, 1.17-1.48, p<0.001), acute kidney injury requiring hemodialysis (OR 3.17, 95% CI, 2.64-3.80, p< 0.001) and major bleeding (OR 1.12, 95% CI 1.05-1.19, p<0.001). Patients with CKD underwent conservative (31.08% vs 36.73%, p<0.0001) and invasive procedures (14.73% vs 23.55%, p<0.0001) less often. PAD-CLI with CKD was associated with major (20.54% vs. 16.17%, OR 1.04; p<0.0001) and minor (26.87% vs. 19.53%, OR 1.2, p<0.0001) amputations more often. Conclusion: Patients admitted for PAD-CLI with concomitant CKD have significantly higher in-hospital mortality as compared to patients without CKD. Moreover, patients with CKD and PAD-CLI are less likely to receive revascularization and more likely to undergo amputation

Abstract 4135092: Prolonged Procedure Time and Its Association with Peri-Procedural Complications in Endovascular Therapy for Symptomatic Lower Extremity Arterial Disease

Background: Prolonged operative times in surgical procedures have been significantly associated with an increased risk of complications. However, the impact of prolonged procedure time of peri-procedural complications in patients undergoing endovascular therapy (EVT) for symptomatic lower extremity arterial disease (LEAD) has not been systematically evaluated. Aims: To determine the association between prolonged procedure time and peri-procedural complications in patients undergoing EVT for symptomatic LEAD. Methods: Data from a nationwide EVT registry in Japan (J-EVT) between 2021 and 2022 were analyzed. The outcome measure was peri-procedural complications defined as a composite of perioperative death, major bleeding, contrast nephropathy, myocardial infarction, ischemic stroke, and major amputation. Procedure time was categorized into four clinically relevant groups (≤59, 60–119, 120–179, and ≥180 minutes). The logistic regression model was developed to investigate the risk of peri-procedural complications across subgroups of procedure time with the shortest subgroup (≤59 minutes) set as the reference category. Results: A total of 47,301 patients (average age: 75±9 years, male: 69.0%, chronic limb-threatening ischemia [CLTI]: 51.0%) undergoing EVT for symptomatic LEAD were analyzed. Notable comorbidities included diabetes mellitus at 60.6% and dialysis at 29.9%, respectively. A history of coronary artery disease was noted in 40.7% of the participants. The median procedure time (interquartile range) was 110 (74–161) minutes. A total of 431 patients (0.9%) experienced perioperative complications. The perioperative complications included 48 deaths, 277 cases of major bleeding, 28 cases of contrast nephropathy, 10 myocardial infarctions, 16 ischemic strokes and 72 major amputations. After adjusting for patient and limb characteristics, and hospital and operator volumes, the odds ratios for perioperative complications were 1.21 (P=0.45) for 60–119 minutes, 2.36 (P=0.001) for 120–179 minutes, and 5.31 (P<0.001) for ≥180 minutes with the shortest subgroup (<59 min) set as the reference. Conclusions: Prolonged procedure time of EVT for symptomatic LEAD was significantly associated with an increased risk of perioperative complications.

Abstract 4138488: Association Between Guideline-directed Medical Therapy and Reintervention Risk at 2 Years Following Peripheral Vascular Interventions

Introduction: Patients with peripheral artery disease (PAD) undergoing peripheral vascular interventions (PVI) face frequent reinterventions. The association between the use of guideline-directed medical therapy (GDMT) and reintervention risk is unclear, we therefore aimed to study the association between GDMT and 2-year reintervention risk using the largest national vascular registry. Methods: PVI procedures in patients with claudication or chronic limb-threatening ischemia between 2017-2018 were abstracted from the Vascular Quality Initiative (VQI) registry. GDMT was defined as statin, antiplatelet, and ACE/ARB if hypertensive prescribed at discharge. Reintervention was obtained from Medicare claims data. Propensity score of no GDMT vs. GDMT was calculated using 22 preprocedural variables followed by 1:1 matching of patients. The 2-year cumulative incidence of reintervention and subhazard ratios (sHR) for 2-year reintervention risk in no GDMT vs. GDMT were assessed using Aalen-Johansen method and Fine-Gray model, respectively, to account for the competing risk of death. Results: A total of 13,244 patients (6,622 by GDMT group) were included after 1:1 matching (mean age 72.0 ± 9.9, female 38.9%, white 79.4% Black or African American 15.3%) . At 2 years, the cumulative incidence of reintervention was 43.0% (95% CI 41.0%-44.9%) for patients with no GDMT vs. 41.2% (95%CI 39.4-43.0) for the GDMT group (P=0.293). Not receiving GDMT was not associated with 2-year risk of reintervention (sHR: 1.03 95%CI 0.97-1.10; P=0.293). Conclusion: Around 40% of patients undergoing a PVI will have a reintervention at 2 years. The receipt of GDMT at discharge was not associated with a lower reintervention risk at 2 years, as currently assessed. Further granular measures of GDMT should integrate adherence information, as well as information on other lifestyle and cardiovascular risk management to obtain a more complete assessment of a potential association with reintervention risk.

Abstract 4147628: A Mixed Methods Analysis of Patient Knowledge in Peripheral Artery Disease

Introduction: Patient knowledge of lower extremity peripheral artery disease (PAD) is low compared to other cardiovascular diseases. Research Questions/Hypothesis: We hypothesize that demographic and socioeconomic factors impact patient knowledge of PAD. Goals/Aims: To obtain qualitative description of and identify factors associated with patient knowledge of PAD. Methods/Approach: We performed a convergent parallel mixed methods study of participants with an established PAD diagnosis. Participants completed an 87-item survey assessing demographics, awareness of PAD diagnosis, and PAD knowledge. Functional health literacy (FHL) was measured using the short Test of Functional Health Literacy Assessment. Multivariable linear regression was used to identify factors associated with PAD knowledge scores. Semi-structured interviews were used to describe understanding of PAD. Transcripts were analyzed with inductive and deductive coding, and a constant comparative approach was used to identify themes. Results/Data: There were 91 participants (77.2% response rate, 49.5% female, 29.7% Black, mean age 68.6 years). Most participants (51.7%) had chronic limb-threatening ischemia and 17.6% had a previous major amputation. While 21.3% had poor FHL and 24.4% were unaware of their PAD diagnosis, the average knowledge score was 79.1%. On bivariate analysis, non-White race, non-ambulatory status, poor FHL, lack of awareness of PAD diagnosis, and not knowing the chronicity of diagnosis were inversely associated with knowledge score. Multivariate linear regression showed that poor FHL, non-White race, and not knowing the chronicity of PAD diagnosis were independently associated with low PAD knowledge. Qualitative analysis of 22 participants revealed that patients have difficulty understanding the name “PAD”, confuse PAD with other comorbidities, and have incorrect beliefs about PAD despite high knowledge scores. Conclusions: Knowledge of PAD is associated with health literacy. However, patients have incorrect beliefs and difficulty understanding the terminology associated with PAD despite a high average knowledge score. Knowledge scores may not adequately reflect understanding. Future research will focus on optimizing patient education, identifying strategies to appropriately gauge patient understanding, and understanding the association between knowledge and behavior in PAD.

Enhancing vascular surgery outcomes through geriatric co-management: a study on the impact of the POPS team

Introduction Peripheral arterial disease (PAD) involves atherosclerotic stenosis and occlusion of lower leg arteries, leading to significant disability, high cardiovascular and cerebrovascular morbidity and mortality. Critical limb ischemia (CLI) is the most severe form of PAD. With the UK's aging population set to increase, the prevalence of PAD and the burden on vascular teams are expected to rise. This study evaluates the impact of regular input from the Proactive Care of Older People Undergoing Surgery (POPS) team on vascular surgery outcomes. Methods This prospective cohort study examined the impact of Care of the Elderly (CoE) input on predefined parameters, focussing primarily on the length of stay (LoS) over 12 months. Data included baseline demographics, comorbidities, frailty scores (assessed using the Rockwood frailty score), LoS and referrals to medical specialties. A retrospective pilot study of 50 consecutive patients indicated a need for CoE input, showing higher local LoS compared with the national average. Results Patients in both pilot and project groups were matched for comorbidities, frailty scores and interventions. Despite higher mean age and a greater proportion of patients aged 75+ years in the project group, the study aimed to reduce LoS. Post-quality improvement project implementation, LoS beyond fit-for-discharge decreased from 11.7 days to 9 days in 6 months and to 6 days after 12 months. Referrals to medical specialties decreased from 77% to 40%, and new diagnoses on discharge increased from 28% to 37%. Conclusions CoE team input in vascular surgery patient care significantly improved outcomes, reducing LoS and medical specialty referrals, demonstrating cost-effectiveness and suggesting a feasible multidisciplinary approach for other regions.

Abstract 4129523: MicroRNA-1282 Rescues Diabetic Limb Ischemia Via a SERF2-Protein Aggregation Pathway

Introduction: Patients with diabetes are at higher risk of chronic limb-threatening ischemia (CLTI), a severe form of peripheral artery disease (PAD) causing restricted blood flow to the lower limbs due, in part, to impaired angiogenesis. However, the role of microRNAs (miRNAs) in diabetic CLTI remains poorly understood. By integrating plasma miRNA sequencing data from PAD patients with diabetes with a diabetic CLTI mouse model, we have recently identified the conserved miRNA miR-1282 that is in cis-antisense orientation to SERF2, a gene associated with amyloid aggregation. Therefore, we hypothesize that miR-1282 orchestrates endothelial angiogenesis and proteostasis during diabetic CLTI. Methods: Using miR-1282 overexpression or SERF2 knockdown studies, we characterized mouse orthologs of human miR-1282 and SERF2 for angiogenesis, apoptosis, protein aggregation, and oxidative stress in diabetic mouse skeletal muscle endothelial cells (ECs). In vivo, miR-1282 mimics were delivered intramuscularly to assess their impact on blood flow recovery, angiogenesis, and protein aggregation. Mechanistic insights in ECs were gained via RNA-seq, predictive algorithms, and proteomic analyses. Results: miR-1282 inhibited the expression of its cis-antisense target SERF2 by 98%. miR-1282 is a hypoxia-induced endothelial-enriched miRNA, and its expression was inversely correlated with SERF2 expression. miR-1282 levels were markedly reduced after femoral artery ligation (FAL) in diabetic db/db mice. Overexpression of miR-1282 or SERF2 knockdown enhanced angiogenesis and reduced protein aggregation, apoptosis, and oxidative stress in both normal and hypoxic conditions in vitro. Delivery of miR-1282 mimics in db/db mice improved blood flow recovery by 108% and angiogenesis by 98%, and reduced protein aggregation by 48% and tissue necrosis. Coupling RNA-seq profiling and prediction algorithms of ECs upon miR-1282 overexpression or SERF2 knockdown revealed EREG, BAG5, CASP3, ARG1, and HSP90AA1 as potential downstream regulators. Pathway enrichment analysis implicated inhibition of endothelial apoptosis, ER stress, and protein stability among the most dysregulated processes. Conclusion: A novel mouse ortholog of human miR-1282 augments endothelial functions and diminishes protein aggregation in diabetic CLTI via suppression of its cis-antisense target SERF2. These findings uncover new potential therapeutic targets in treating diabetic CLTI.

Role of DDR1 in Regulating MMPs in External Root Resorption

Human periodontal ligament cells (hPDLCs) express matrix metalloproteinases (MMPs), a group of enzymes responsible for the destruction of most extracellular matrix proteins in dental tissues, especially MMP-1, MMP-2, and MMP-13. Exploring the regulatory mechanism of MMPs is crucial for understanding external root resorption (ERR), one of the most severe complications, along with substantial loss of dental tissue, induced by trauma, pulpal infection, tooth bleaching, and orthodontic treatment, etc. Discoidin domain receptor 1 (DDR1), a cell surface receptor binding to collagen, has the potential to regulate the expression of MMP-1, MMP-2, and MMP-13, but the mechanism remains unclear. Thus, the present study aimed to investigate the connection and underlying mechanism between MMP-1, MMP-2, MMP-13, and DDR1 in hPDLCs. Our post-replantation ERR model revealed that Mmp-1, Mmp-2, Mmp-13, and Ddr1 all increased in the sites of ERR. hPDLCs with DDR1 knockdown exhibited a substantial reduction in MMP-1, MMP-2, and MMP-13 expression. To further confirm the underlying mechanism, we conducted further in vitro experiments, including RNA sequencing, RNA interference, RT-qPCR, Western blotting, and ELISA. Based on our results, MMP-1 was positively regulated by the Smad2/3 and MEK-ERK1/2 pathways and negatively regulated by the PI3K-Akt pathway through CCN2. MMP-2 and MMP-13 were positively regulated by the Smad2/3 pathway. MMP-13 was positively regulated by the MEK-ERK1/2 and PI3K/Akt signaling pathways. Collectively, DDR1 is a potent regulator of MMP-1, MMP-2, and MMP-13 expression through the Smad2/3, MEK-ERK1/2, and PI3K/Akt signaling pathways. Clarifying the significance and underlying mechanism by which DDR1 is involved in ERR might bring the chances to hinder the pathogenic process of ERR, hence reducing its incidence rate.

Brain Abscess Causes Brain Damage With Long-Lasting Focal Cerebral Hypoactivity that Correlates With Abscess Size: A Cross-Sectional 18F-Fluoro-Deoxyglucose Positron Emission Tomography Study

BACKGROUND AND OBJECTIVES: Bacterial brain abscesses may have long-term clinical consequences, eg, mental fatigue or epilepsy, but long-term structural consequences to the brain remain underexplored. We asked if brain abscesses damage brain activity long term, if the extent of such damage depends on the size of the abscess, and if the abscess capsule, which is often left in place during neurosurgery, remains a site of inflammation, which could explain long-lasting symptoms in patients with brain abscess. METHODS: 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), electroencephalography, and MRI were performed 2 days to 9 years after neurosurgery for bacterial brain abscess. RESULTS: FDG-PET/CT revealed hypometabolism in the neocortex or cerebellum overlying the previous bacterial abscess in 38 of 40 patients. The larger the abscess, the greater was the extent of the subsequent hypometabolism (r = 0.63; p = 3 × 10−5). In 9 patients, the extent of subsequent hypometabolism seemed to coincide with the extent of peri-abscess edema in the acute phase. Follow-up MRI after ≥1 year in 9 patients showed focal tissue loss and gliosis. In 13 patients with abnormal electroencephalography recordings, abnormalities extended beyond the cerebral lobe affected by the abscess, indicating damage to wider brain networks. The abscess capsule had an FDG signal indicating inflammation only during the first week after neurosurgical pus drainage. CONCLUSION: The bigger a brain abscess is allowed to grow, the more extensive is the long-term focal reduction in brain activity. This finding emphasizes the need for rapid neurosurgical intervention. The abscess capsule does not display long-lasting inflammation and probably does not explain long-term symptoms after brain abscess.

Neuromuscular Regeneration of Volumetric Muscle Loss Injury in Response to Agrin‐Functionalized Tissue Engineered Muscle Grafts and Rehabilitative Exercise

AbstractNeuromuscular deficits compound the loss of contractile tissue in volumetric muscle loss (VML). Two avenues for promoting recovery are neuromuscular junction (NMJ)‐promoting substrates (e.g., agrin) and endurance exercise. Although mechanical stimulation enhances agrin‐induced NMJ formation, the two modalities have yet to be evaluated combinatorially. It is hypothesized that the implantation of human myogenic progenitor‐seeded tissue‐engineered muscle grafts (hTEMGs) in combination with agrin treatment and/or exercise will enhance neuromuscular recovery after VML. The hTEMGs alone transplant into VML defects promote significant regeneration with minimal scarring. A sex‐appropriate, low‐intensity continuous running exercise paradigm increases acetylcholine receptor (AChR) cluster density in male mice twofold relative to hTEMG alone after 7 weeks of treadmill training (p < 0.05). To further promote neuromuscular recovery, agrin is incorporated into the scaffolds via covalent tethering. In vitro, agrin increases the proliferation of hMPs, and trends toward greater myogenic maturity and AChR clustering. Upon transplantation, both hTEMGs + agrin and hTEMGs + exercise induce near 100% recovery of muscle mass and increase twitch and tetanic force output (p > 0.05). However, agrin treatment in combination with exercise produces no additional benefit. These data highlight the unprecedented regenerative potential of using hTEMGs together with either agrin or exercise supplementation to treat VML injuries.

Genomic and Bioinformatics Analysis of Familial Partial Lipodystrophy Type 3 Identified in a Patient with Novel PPARγ Mutation and Robust Response to Pioglitazone

Familial partial lipodystrophies (FPLDs) are very rare inherited disorders characterized by partial loss of adipose tissue from the upper and lower extremities. At least seven subtypes of FPLD have been identified and are mostly dominantly inherited. FPLD type 3 is caused by mutations in the PPARγ gene, which encodes for the protein peroxisome proliferator-activated receptor gamma (PPARγ). We identified a Saudi female with PFLD3 presented with partial lipoatrophy, uncontrolled diabetes, severe hypertriglyceridemia, and recurrent pancreatitis. The clinical and biochemical findings in this proband were described before and after treatment with Pioglitazone in addition to the conventional treatment. DNA extraction and whole exome sequencing (WES) were performed to detect the variant. The mutant gene was subjected to Sanger analysis to confirm the results. We applied five specific computational prediction tools to assess the pathogenicity of variation, namely the MT, DANN, CADD, BayesDel, and fitCons tools. We assessed protein modeling and stability with the AlphaFold-generated structures for both wild-type and mutant proteins. Finally, we conducted molecular docking using the AutoDock Vina virtual docking. Upon whole exome sequencing, a c.1024C>T p.(Gln342Ter) missense mutation was detected in the PPARγ gene associated with FPLD3. This variant is a novel mutation that has not been described in all genome databases. Sanger analysis confirmed the heterogenicity and pathogenicity of this variant. All five computational prediction tools indicate that this variant is considered highly pathogenic. Our patient showed a dramatic response to Pioglitazone, a synthetic PPARγ agonist. From structural modeling, we found that the enhanced binding affinity of the mutant PPARγ protein to Pioglitazone likely improves the activation of PPARγ, enhancing its transcriptional activity and resulting in better clinical outcomes. These findings extend the spectrum of PPARγ mutations responsible for FPLD3 and highlight the potential for personalized treatment strategies based on genetic mutations.

The effects of disease lesions and amoxicillin treatment on the physiology of SCTLD-affected corals

Metrics of coral physiology can be used to identify changes in coral health due to environmental stressors or management actions. One of the most unprecedented stressors to Caribbean corals is the spread of stony coral tissue loss disease (SCTLD), which also resulted in the novel management action of in-water amoxicillin treatments on active disease lesions. Though highly effective at halting lesions and preventing coral mortality, possible unintended consequences of topical application of amoxicillin to coral tissue were unknown. We used in-water instrumentation to measure and compare photosynthesis (P), respiration (R), P/R ratios, and calcification of corals that were visually healthy, actively diseased, and diseased but treated with amoxicillin paste. Measurements occurred across three time points and two species – Orbicella faveolata and Montastraea cavernosa. Across all metrics, treatment type did not cause significant differences, indicating that neither SCTLD lesions nor amoxicillin treatments impacted the physiology of adjacent tissues. There were significant variations among time points, which may have resulted from changes to coral health across the reef, variations due to environmental variables, or other unknown factors. We suggest that physiological metrics could be an interesting way to fate track coral health across short- and long-term timeframes. We also conclude that amoxicillin treatments as a tool to halt SCTLD are not detrimental to respiration, photosynthesis, or calcification rates of adult corals.

Laparoscopic versus open lumbar sympathectomy in critical limb threatening ischemia patients in Egypt

PurposeThe treatment of critical limb-threatening ischemia (CLTI) is revascularization. Lumbar sympathectomy (LS) could be attempted when this is not amenable. Using laparoscopic techniques to perform LS adds the advantages of minimally invasive surgery.MethodsTwenty-four patients, presenting with non-reconstructable CLTI and rest pain, were randomly divided into group I (14 patients) who underwent retroperitoneoscopic lumbar sympathectomy (RPLS) and group II (10 patients) who had conventional open lumber sympathectomy (COLS).ResultsRPLS patients had shorter hospital stays, fewer intraoperative complications, and less postoperative pain. However, the mean operative time was significantly longer (86.4 ± 9.1 min, p-value: 0.02) in the RPLS group but decreased with each subsequent case after that. The differences in post-operative capillary refill time, ABI, TBI, and TcPO2 were not statistically significant between both groups (p-values: 0.97, 0.13, 0.32, 0.10, respectively). However, the difference in the quality-of-life score was statistically significant; the mean (± SD) SF-36 score increased from 48 ± 6.8 to 81 ± 4.4 (p-value < 0.001) in RPLS group compared to 52 ± 8.8 to 59 ± 1.2 (p-value: 0.52) in COLS group.ConclusionRPLS is feasible, safe, and has the advantages of minimally invasive surgery: minimal blood loss, less intraoperative complications, shorter hospital stay, and less postoperative pain. However, the operative time in RPLS cases is longer than in the COLS; training on the procedure is recommended to improve the learning curve.

Current Advances and Challenges in Stem Cell-Based Regenerative Therapy for Chronic Limb-Threatening Ischemia

Current Advances and Challenges in Stem Cell-Based Regenerative Therapy for Chronic Limb-Threatening Ischemia