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1.
Plast Reconstr Surg Glob Open ; 12(5): e5709, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38798933

RESUMO

Background: Due to variations in perforator vasculature, deep inferior epigastric artery perforator (DIEP) flap preoperative imaging can minimize operative time required to locate the most suitable perforators. Dedicated computed tomography angiography (CTA) has been the gold standard; however, many patients have already undergone a staging computed tomography (CT) per oncologic workup. The benefits from CTA may also be realized with a staging CT or CT with IV contrast. Methods: Ten patients who underwent DIEP flap reconstruction with staging CT and CTA within 3 years of one another were included in this study. Reviewers evaluated axial views of both imaging modalities separately to identify each visible perforator in reference to the pubic symphysis from the xiphoid to the pubic symphysis. An intraclass correlation coefficient (ICC) was used to determine agreement in location of perforators between the two imaging studies. Statistical analysis was performed using an ICC and Wilcoxon signed rank-tests. Results: The identified perforators within the patient cohort had an excellent correlation between their location on CT and CTA based upon ICC. The mean number of perforators identified in the CT group was 15.3 (SD 4.9) and in the CTA group was 18.8 (SD 6.4), which was not statistically different (P = 0.247). Conclusions: CT has similar efficacy in identifying number of perforators and perforator location to dedicated CTA for preoperative planning in DIEP flaps. This has the potential for decreased patient contrast and ionizing radiation exposure as well as improved patient and healthcare resource utilization.

3.
J Genet Couns ; 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907432

RESUMO

Germline genetic testing for cancer predisposition genes has become an essential component of cancer treatment and risk reduction. The National Comprehensive Cancer Network (NCCN) releases annual genetic testing guidelines that identify characteristics of patients that could be affected by a hereditary cancer syndrome. These guidelines have broadened over time and the implications for past patients of cancer genetics clinics are not well understood. This study is a retrospective chart review aimed at determining the percentage and characteristics of past patients that meet updated NCCN guidelines (Breast, Ovarian, and Pancreas [BOP] v1.2022 and Colorectal [CRC] v1.2021), patients that attended a follow-up appointment, and patients who went on to receive genetic testing. Clinical data and characteristics were compared between the study population as a whole and the cohort of patients that met updated NCCN guidelines BOP v1.2022 and CRC v1.2021. The study population consisted of 280 patients with 76 (27.1%) patients meeting updated NCCN guidelines BOP v1.2022 and CRC v1.2021. The year of initial cancer genetic counseling appointment was statistically significant (p = 0.023) with patients more likely to meet NCCN guidelines BOP v1.2022 and CRC v1.2021 with earlier initial cancer genetic counseling appointments. In the cohort that met updated NCCN guidelines BOP v1.2022 and CRC v1.2021, the most common reason was a change in the NCCN guidelines (BOP or CRC) (54/76, 71.1%) with triple-negative breast cancer diagnosed at any age being the most impactful guideline change (19/54, 35.2%). Twenty-one patients attended a follow-up appointment (7.5%) and of those that received genetic testing (17/21, 81%) most received negative results (13/17, 61.9%), with one pathogenic, low penetrance result (1/17, 5.9%, CHEK2 p.I157T). Provider-initiated follow-up was attributed to most follow-up appointments (16/21, 76.2%) implying patients do not tend to follow-up on their own. Education to non-genetics providers as well as targeted implementation of follow-up protocols possibly managed by genetic counseling assistants and utilizing electronic medical record (EMR) patient messaging could lead to improved patient follow-up.

4.
Health Serv Res ; 58(6): 1256-1265, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700549

RESUMO

OBJECTIVE: To evaluate a health system-wide intervention distributing free home-disposal bags to surgery patients prescribed opioids. DATA SOURCES AND STUDY SETTING: We collected patient surveys and electronic medical record data at an academic health system. STUDY DESIGN: We conducted a prospective observational study. The bags were primarily distributed at pharmacies, though pharmacists delivered bags to some patients. The primary outcome was disposal of leftover opioids (effectiveness). Secondary outcomes were patient willingness to dispose and factors associated with disposal (effectiveness), recalling receipt of the bag (reach), and recalling receipt of bags and disposal over time (maintenance). We used a modified Poisson regression to evaluate the relative risk of disposal. Inverse probability of treatment weighting, based on propensity scores, was used to account for differences between survey responders and non-responders and reduce nonresponse bias. DATA COLLECTION/EXTRACTION METHODS: From August 2020 to May 2021, we surveyed patients 2 weeks after discharge (allowing for home opioid use). Eligibility criteria were age ≥18, English being primary language, valid email address, hospitalization ≤30 days, discharge home, and an opioid prescription sent to a system pharmacy. PRINCIPAL FINDINGS: We identified 5134 patients with 2174 completing the survey (response rate 42.3%). Among respondents, 1375 (63.8%) recalled receiving the disposal bag. Among 1075 respondents with leftover opioids, 284 (26.4%) disposed, 552 (51.3%) planned to dispose, 79 (7.4%) did not plan to dispose, 69 (6.4%) had undecided, and 91 (8.5%) had not considered disposal. Recalling receipt of the bag (incidence rate ratio [IRR] 1.25, 95% confidence interval [CI] 1.13-1.37) was positively associated with disposal. Patients who used opioids in the last year were less likely to dispose (IRR 0.82, 95% CI 0.73-0.93). Disposal rates remained stable over the study period while recalling receipt of bags trended up. CONCLUSIONS: A pragmatic implementation of a disposal intervention resulted in lower disposal rates than prior trials.


Assuntos
Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/uso terapêutico , Hospitalização , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Alta do Paciente , Estudos Prospectivos , Adolescente , Adulto
5.
Surg Open Sci ; 13: 27-34, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37351188

RESUMO

Background: Multimodal perioperative patient education and expectation-setting can reduce post-operative opioid use while maintaining pain control and satisfaction. As part of a quality-improvement project, we developed a standardized model for perioperative education built upon the American College of Surgeons (ACS) Safe and Effective Pain Control After Surgery (SEPCAS) brochure to improve perioperative education regarding opioid use and pain control. Material and methods: Our study was designed within the Define, Measure, Analyze, Improve, Control (DMAIC) quality-improvement framework. Patients were surveyed about the adequacy of their perioperative education regarding pain control and use of prescription opioid medication. After gathering baseline data, a multimodal educational intervention based on the SEPCAS brochure was implemented. Survey responses were then compared between groups. Results: Twenty-seven subjects were included from the pre-intervention period, and thirty-nine were included from the post-intervention period (n = 66). Those in the post-intervention period were more likely to report receiving the appropriate amount of education regarding recognizing the signs of opioid overdose and how to safely store and dispose of opioid medications. The majority of patients who received the SEPCAS brochure reported that it was useful in their post-operative recovery and that it should be given to every patient undergoing surgery. Conclusions: The ACS SEPCAS brochure is an effective tool for improving patient preparation to safely store and dispose of their opioid medication and recognize the signs of opioid overdose. The brochure was also well received by patients and perceived as an effective educational material.

6.
J Surg Educ ; 80(6): 786-796, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36890045

RESUMO

OBJECTIVE: In order to effectively create and implement an educational program to improve opioid prescribing practices, it is important to first consider the unique perspectives of residents on the frontlines of the opioid epidemic. We sought to better understand resident perspectives on opioid prescribing, current practices in pain management, and opioid education as a needs assessment for designing future educational interventions. DESIGN: This is a qualitative study using focus groups of surgical residents at 4 different institutions. SETTING: We conducted focus groups using a semistructured interview guide in person or over video conferencing. The residency programs selected for participation represent a broad geographic range and varying residency sizes. PARTICIPANTS: We used purposeful sampling to recruit general surgery residents from the University of Utah, University of Wisconsin, Dartmouth-Hitchcock Medical Center, and the University of Alabama at Birmingham. All general surgery residents at these locations were eligible for inclusion. Participants were assigned to focus groups by residency site and their status as junior (PGY-2, PGY-3) or senior resident (PGY-4, PGY-5). RESULTS: We completed 8 focus groups with a total of 35 residents included. We identified 4 main themes. First, residents relied on clinical and nonclinical factors when making decisions about opioid prescribing. However, hidden curricula based on unique institutional cultures and attending preferences heavily influenced residents' prescribing practices. Second, residents acknowledged that stigma and biases towards certain patient groups influenced opioid prescribing practices. Third, residents encountered barriers within their health systems to evidence-based opioid prescribing. Fourth, residents did not routinely receive formal education on pain management or opioid prescribing. Residents recommended several interventions to improve the current state of opioid prescribing, including standardized prescribing guidelines, improved patient education, and formal training during the first year of residency. CONCLUSIONS: Our study highlighted several areas of opioid prescribing that can be improved upon through educational interventions. These findings can be used to develop programs aimed at improving residents' opioid prescribing practices, both during and after training, and ultimately the safe care of surgical patients. ETHICS STATEMENT: This project was approved by the University of Utah Institutional Review Board, ID # 00118491. All participants provided written informed consent.


Assuntos
Cirurgia Geral , Internato e Residência , Humanos , Analgésicos Opioides/uso terapêutico , Epidemia de Opioides , Padrões de Prática Médica , Prescrições de Medicamentos , Inquéritos e Questionários , Currículo , Cirurgia Geral/educação
7.
Sci Adv ; 9(8): eade7864, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36827367

RESUMO

Thermogenesis by uncoupling protein 1 (UCP1) is one of the primary mechanisms by which brown adipose tissue (BAT) increases energy expenditure. UCP1 resides in the inner mitochondrial membrane (IMM), where it dissipates membrane potential independent of adenosine triphosphate (ATP) synthase. Here, we provide evidence that phosphatidylethanolamine (PE) modulates UCP1-dependent proton conductance across the IMM to modulate thermogenesis. Mitochondrial lipidomic analyses revealed PE as a signature molecule whose abundance bidirectionally responds to changes in thermogenic burden. Reduction in mitochondrial PE by deletion of phosphatidylserine decarboxylase (PSD) made mice cold intolerant and insensitive to ß3 adrenergic receptor agonist-induced increase in whole-body oxygen consumption. High-resolution respirometry and fluorometry of BAT mitochondria showed that loss of mitochondrial PE specifically lowers UCP1-dependent respiration without compromising electron transfer efficiency or ATP synthesis. These findings were confirmed by a reduction in UCP1 proton current in PE-deficient mitoplasts. Thus, PE performs a previously unknown role as a temperature-responsive rheostat that regulates UCP1-dependent thermogenesis.


Assuntos
Fosfatidiletanolaminas , Prótons , Camundongos , Animais , Proteína Desacopladora 1/metabolismo , Fosfatidiletanolaminas/metabolismo , Mitocôndrias/metabolismo , Termogênese , Obesidade/metabolismo , Trifosfato de Adenosina/metabolismo , Camundongos Knockout
8.
Health Educ Behav ; 50(2): 281-289, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-34963358

RESUMO

BACKGROUND: Patients rarely dispose of left-over opioids after surgery. Disposal serves as a primary prevention against misuse, overdose, and diversion. However, current interventions promoting disposal have mixed efficacy. Increasing disposal in rural communities could prevent or reduce the harms caused by prescription opioids. AIMS: Identify barriers and facilitators to disposal in the rural communities of the United States Mountain West region. METHODS: We conducted a qualitative description study with 30 participants from Arizona, Idaho, Montana, Nevada, Oregon, Utah, and Wyoming. We used a phronetic iterative approach combining inductive content and thematic analysis with deductive interpretation through the Precaution Adoption Process Model (PAPM). RESULTS: We identified four broad themes: (a) awareness, engagement, and education; (b) low perceived risk associated with nondisposal; (c) deciding to keep left-over opioids for future use; and (d) converting decisions into action. Most participants were aware of the importance of disposal but perceived the risks of nondisposal as low. Participants kept opioids for future use due to uncertainty about their recovery and future treatments, breakdowns in the patient-provider relationship, chronic illness or pain, or potential future injury. The rural context, particularly convenience, cost, and environmental contamination, contributes to decisional burden. CONCLUSIONS: We identified PAPM stage-specific barriers to disposal of left-over opioids. Future interventions should account for where patients are along the spectrum of deciding to dispose or not dispose as well as promoting harm-reduction strategies for those who choose not to dispose.


Assuntos
Analgésicos Opioides , Overdose de Drogas , Estados Unidos , Humanos , Analgésicos Opioides/efeitos adversos , População Rural , Pesquisa Qualitativa , Arizona
9.
J Surg Res ; 281: 155-163, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36155272

RESUMO

INTRODUCTION: Successful recovery after surgery is complex and highly individual. Rural patients encounter greater barriers to successful surgical recovery than urban patients due to varying healthcare and community factors. Although studies have previously examined the recovery process, rural patients' experiences with recovery have not been well-studied. The rural socioecological context can provide insights into potential barriers or facilitators to rural patient recovery after surgery. METHODS: We conducted semi-structured qualitative interviews with a purposeful sample of 30 adult general surgery patients from rural areas in the Mountain West region of the United States. We used the socioecological framework to analyze their responses. Interviews focused on rural participants' experiences accessing healthcare and the impact of family and community support during postoperative recovery. Interviews were transcribed verbatim and coded using content and thematic analysis. RESULTS: All participants commented on the quality of their rural healthcare systems and its influence on postoperative care. Some enjoyed the trust developed through long-standing relationships with providers in their communities. However, participants described community providers' lack of money, equipment, and/or knowledge as barriers to care. Following surgery, participants recognized that there are advantages and disadvantages to receiving family and community support. Some participants worried about being stigmatized or judged by their community. CONCLUSIONS: Future interventions aimed at improving access to and recovery from surgery for rural patients should take into account the unique perspectives of rural patients. Addressing the socioecological factors surrounding rural surgery patients, such as healthcare, family, and community resources, will be key to improving postoperative recovery.


Assuntos
Acessibilidade aos Serviços de Saúde , População Rural , Adulto , Humanos , Pesquisa Qualitativa
10.
Surg Pract Sci ; 152023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38222465

RESUMO

Background: Surgeon-prescribed opioids contribute to 11% of prescription drug overdoses in the United States (US). With prescription opioids involved in 24% of all opioid-related overdose deaths in 2020, the US Centers for Disease Control and Prevention (CDC) recommends naloxone co-prescribing to patients at high-risk of overdose and death as a harm reduction strategy. We sought to 1) examine naloxone co-prescribing rates to surgical patients (using common post-surgical prescribing amounts) and those with potential risk factors for opioid-related overdoses or adverse events, and 2) identify the factors associated with patients receiving naloxone co-prescriptions. Methods: We conducted a single-institution, retrospective study using the electronic medical records of all patients undergoing surgery at an academic institution between August 2020 and May 2021. We included post-surgical adults prescribed opioids that were sent to a pharmacy in our health system. The primary outcome was the percentage of co-prescribed naloxone in patients prescribed opioids. Results: The overall naloxone co-prescription rate was low (1.7%). Only 14.6% of patients prescribed ≥350 morphine milligram equivalents (MME, equivalent to 46.7 oxycodone 5 mg tablets) and 8.6% of patients using illicit drugs were co-prescribed naloxone. On multivariable analysis, patients who were prescribed >350 MME, used illicit drugs or tobacco, underwent an elective or emergent general surgery procedure, self-identified as Hispanic, or had ASA scores of 2-4 were more likely to receive a naloxone co-prescription. Conclusions: Naloxone co-prescribing after surgery remains low, even for high-risk patients. Harm reduction strategies such as naloxone, safe storage, and disposal of leftover opioids could reduce surgeons' iatrogenic contributions to the worsening US opioid crisis.

12.
Exp Gerontol ; 163: 111804, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35405248

RESUMO

BACKGROUND AND AIMS: Metformin is the most commonly prescribed medication to treat diabetes. Emerging evidence suggests that metformin could have off target effects that might help promote healthy muscle aging, but these effects have not been thoroughly studied in glucose tolerant older individuals. The purpose of this study was to investigate the short-term effects of metformin consumption on skeletal muscle mitochondrial bioenergetics in healthy older adults. METHODS: We obtained muscle biopsy samples from 16 healthy older adults previously naïve to metformin and treated with metformin (METF; 3F, 5M), or placebo (CON; 3F, 5M), for two weeks using a randomized and blinded study design. Samples were analyzed using high-resolution respirometry, immunofluorescence, and immunoblotting to assess muscle mitochondrial bioenergetics, satellite cell (SC) content, and associated protein markers. RESULTS: We found that metformin treatment did not alter maximal mitochondrial respiration rates in muscle compared to CON. In contrast, mitochondrial H2O2 emission and production were elevated in muscle samples from METF versus CON (METF emission: 2.59 ± 0.72 SE Fold, P = 0.04; METF production: 2.29 ± 0.53 SE Fold, P = 0.02). Furthermore, the change in H2O2 emission was positively correlated with the change in type 1 myofiber SC content and this was biased in METF participants (Pooled: R2 = 0.5816, P = 0.0006; METF: R2 = 0.674, P = 0.0125). CONCLUSIONS: These findings suggest that acute exposure to metformin does not impact mitochondrial respiration in aged, glucose-tolerant muscle, but rather, influences mitochondrial-free radical and SC dynamics. CLINICAL TRIAL REGISTRATION: NCT03107884, clinicaltrials.gov.


Assuntos
Metformina , Idoso , Glucose/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Mitocôndrias/metabolismo , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo
14.
Am J Surg ; 224(1 Pt A): 58-63, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34973685

RESUMO

BACKGROUND: Leftover pills from postoperative opioid prescriptions place patients and members of their communities at risk for opioid misuse. We aimed to better understand patients' post-discharge opioid consumption patterns to inform new methods of postoperative opioid prescribing. METHODS: We assessed post-discharge opioid consumption of general surgery patients and assessed the adequacy of discharge opioid prescriptions. We then compared patient opioid consumption to a number of theoretical discharge prescriptions based on different opioid prescribing guidelines and a proposed discharge prescription based on the metric 24-h pre-discharge opioid consumption (PDOC). RESULTS: 62/99 patients (62.6%) returned an opioid log book. Median 24-h PDOC was 22.5 MME (IQR 5.0-45.0) and median discharge prescription size was 15 pills (IQR:10-20). Prescriptions were adequate for 83.7% of patients. The median number of pills used was 3 (IQR:0-11) and median time to opioid cessation was 3 days (IQR:0-5). Actual prescriptions were consistent with national opioid prescribing guidelines. Prescriptions based on the formula 2 × 24-h PDOC would have decreased the number of leftover pills by 7.5 per patient. CONCLUSIONS: Despite prescribing opioids consistent with national opioid prescribing guidelines, patients still receive too many pills. Improved opioid prescribing could be accomplished by use of the formula 2 × 24-h PDOC.


Assuntos
Analgésicos Opioides , Dor Pós-Operatória , Assistência ao Convalescente , Analgésicos Opioides/uso terapêutico , Humanos , Dor Pós-Operatória/tratamento farmacológico , Alta do Paciente , Padrões de Prática Médica
15.
Am J Hosp Palliat Care ; 39(4): 406-412, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34047202

RESUMO

BACKGROUND: Advance care planning (ACP) is recommended for older patients undergoing surgery. ACP consists of creating advance directives (ADs), identifying surrogate decision makers (SDMs), and documenting goals of care. We identified factors associated with documentation of preoperative ACP to identify opportunities to optimize ACP for older surgical patients. METHODS: This was a retrospective study of surgical patients ≥70 years old who underwent elective, high-risk abdominal procedures between 01/2015-08/2019. Clinical data were obtained from our institution's National Surgical Quality Improvement Project database. ACP metrics were extracted from the electronic medical record. We analyzed the data to identify patient factors associated with ACP metrics. We also analyzed whether ACP was more frequent for patients who experienced postoperative complications or death. RESULTS: 267/1,651 patients were included. 97 patients (36%) had an AD available on the day of surgery, 57 (21%) had an SDM identified, and 31 (12%) had a documented goals of care conversation. On multivariable analysis, older age and white race were associated with an increased likelihood of having an AD available on the day of surgery. Women were 1.7 times more likely to have an SDM (p = 0.02). No patient or surgeon factors were significantly associated with goals of care documentation. ACP was not performed more frequently in patients who experienced postoperative complications or death. CONCLUSION: In this series, ACP was not routinely documented for older patients undergoing major surgery. ACP was not more frequent in patients who experienced complications or death, demonstrating the importance of universal preoperative ACP in older patients.


Assuntos
Planejamento Antecipado de Cuidados , Diretivas Antecipadas , Idoso , Comunicação , Documentação , Feminino , Humanos , Estudos Retrospectivos
16.
Ann Surg Open ; 3(4): e223, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36590888

RESUMO

We examined how convenience and financial incentives influence patient willingness to dispose of leftover prescription opioids after surgery. We also identified additional barriers and facilitators to disposal. Background: In the United States, up to 70% of surgical patients are prescribed opioids and up to 92% will have leftover tablets. Most do not dispose of leftover opioids, increasing the risk for opioid-related harm. Current interventions promoting opioid disposal have shown mixed success. Methods: We conducted a mixed methods study using a standard gamble survey and semi-structured interviews. Participants estimated willingness to dispose in 16 scenarios with varying convenience (time requirements of <5, 15, 30, and 60 minutes) and financial incentives ($0, $5, $25, $50). We estimated the likelihood of disposal using a multivariable mixed effects modified Poisson regression model. Semi-structured interviews explored how convenience, financial incentives, and other barriers and facilitators influenced decisions to dispose. Results: Fifty-five participants were surveyed and 42 were interviewed. Most were willing to dispose when the time required was <15 minutes. Few were willing to dispose if the process required 60 minutes, although a $50 financial incentive increased rates from 9% to 36%. Anxiety about future pain, opioid scarcity, recreational use, family safety, moral beliefs, addiction, theft, and environmental harm also influenced decision-making. Conclusions: Interventions promoting opioid disposal should focus on convenience, but the selective use of financial incentives can be effective. Tailoring interventions to individual barriers and facilitators could also increase disposal rates.

18.
JBJS Case Connect ; 11(3)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449451

RESUMO

CASE: A 21-year-old male division I collegiate athlete presented for right knee pain, effusion, and mechanical symptoms. The patient was found to have 2.4 × 2-cm medial patellar facet, 1 × 0.8-cm central trochlea, and 2.5 × 3-cm lateral femoral condyle articular cartilage defects on arthroscopy. The patient was treated with a matrix-induced autologous chondrocyte implantation (MACI) procedure for all 3 lesions. At 9 months postoperatively, the patient returned to full American football activities and remains asymptomatic 16 months postoperatively. CONCLUSION: Multiple lesions and lesions involving the patellofemoral joint can be treated with a MACI procedure with short-term promising results in high-demand athletes.


Assuntos
Futebol Americano , Adulto , Artroscopia , Atletas , Condrócitos , Humanos , Masculino , Transplante Autólogo , Adulto Jovem
19.
J Am Heart Assoc ; 10(1): e016696, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33327730

RESUMO

Background Expression of receptor for advanced glycation end products (RAGE) plays an important role in diabetic peripheral artery disease. We proposed to show that treatment with an antibody blocking RAGE would improve hind limb perfusion and muscle viability in diabetic pig with femoral artery (FA) ligation. Methods and Results Purpose-bred diabetic Yucatan minipigs with average fasting blood sugar of 357 mg/dL on insulin to maintain a glucose range of 300 to 500 mg/dL were treated with either a humanized monoclonal anti-RAGE antibody (CR-3) or nonimmune IgG. All pigs underwent intravascular occlusion of the anterior FA. Animals underwent (201Tl) single-photon emission computed tomography/x-ray computed tomography imaging on days 1 and 28 after FA occlusion, angiogenesis imaging with [99mTc]dodecane tetra-acetic acid-polyethylene glycol-single chain vascular endothelial growth factor (scVEGF), muscle biopsies on day 7, and contrast angiogram day 28. Results showed greater increases in perfusion to the gastrocnemius from day 1 to day 28 in CR-3 compared with IgG treated pigs (P=0.0024), greater uptake of [99mTc]dodecane tetra-acetic acid-polyethylene glycol-scVEGF (scV/Tc) in the proximal gastrocnemius at day 7, confirmed by tissue staining for capillaries and vascular endothelial growth factor A, and less muscle loss and fibrosis at day 28. Contrast angiograms showed better reconstitution of the distal FA from collaterals in the CR-3 versus IgG treated diabetic pigs (P=0.01). The gastrocnemius on nonoccluded limb at necropsy had higher 201Tl uptake (percentage injected dose per gram) and reduced RAGE staining in arterioles in CR-3 treated compared with IgG treated animals (P=0.04). Conclusions A novel RAGE-blocking antibody improved hind limb perfusion and angiogenesis in diabetic pigs with FA occlusion. Contributing factors are increased collaterals and reduced vascular RAGE expression. CR-3 shows promise for clinical treatment in diabetic peripheral artery disease.


Assuntos
Indutores da Angiogênese/farmacologia , Anticorpos Monoclonais/farmacologia , Angiopatias Diabéticas , Doença Arterial Periférica , Receptor para Produtos Finais de Glicação Avançada , Angiografia/métodos , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/metabolismo , Descoberta de Drogas/métodos , Produtos Finais de Glicação Avançada/metabolismo , Membro Posterior/irrigação sanguínea , Músculo Esquelético/irrigação sanguínea , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/metabolismo , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Receptor para Produtos Finais de Glicação Avançada/imunologia , Suínos , Porco Miniatura , Resultado do Tratamento
20.
J Orthop Case Rep ; 11(9): 86-89, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35415176

RESUMO

Introduction: There are reports which describe multiple lytic lesions seen on X-ray resulting from a non-tuberculous Mycobacterium skeletal infection in immunocompetent adults and children. AdditionallyIn addition, similar multifocal lesions have also been described in chronic recurrent multifocal osteomyelitis (CRMO) which is more common in children but has have rarely been reported in adults. We present a case of a 47-year-old female who presented with multiple osteolytic lesions and discuss how her diagnosis overlaps with CRMO and multifocal non-tuberculous osteomyelitis associated with Mycobacterium avium complex (MAC). Case Report: A 47-year-old female presented with a mass at her left sternoclavicular joint. Biopsy of the lesion showed acute and chronic inflammation suggesting osteomyelitis. The patient was on intravenousIV antibiotics with some improvement. After three 3 ½ and a half months, she was having knee pain and imaging showed another lesion and a bone scan found a third. Delayed cultures grew Mycobacterium avium complexMAC but ultimately the patient improved when she was taking naproxen for multifocal osteomyelitis. Conclusion: Multifocal lytic lesions on imaging in an adult can be multifocal osteomyelitis that, like in pediatric patients, may be treated best with nonsteroidal anti-inflammatory medications as with the patient in this case.

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