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BACKGROUND: Primary biliary cholangitis is a rare, chronic cholestatic liver disease characterized by the destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. Whether elafibranor, an oral, dual peroxisome proliferator-activated receptor (PPAR) α and δ agonist, may have benefit as a treatment for primary biliary cholangitis is unknown. METHODS: In this multinational, phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients with primary biliary cholangitis who had had an inadequate response to or unacceptable side effects with ursodeoxycholic acid to receive once-daily elafibranor, at a dose of 80 mg, or placebo. The primary end point was a biochemical response (defined as an alkaline phosphatase level of <1.67 times the upper limit of the normal range, with a reduction of ≥15% from baseline, and normal total bilirubin levels) at week 52. Key secondary end points were normalization of the alkaline phosphatase level at week 52 and a change in pruritus intensity from baseline through week 52 and through week 24, as measured on the Worst Itch Numeric Rating Scale (WI-NRS; scores range from 0 [no itch] to 10 [worst itch imaginable]). RESULTS: A total of 161 patients underwent randomization. A biochemical response (the primary end point) was observed in 51% of the patients (55 of 108) who received elafibranor and in 4% (2 of 53) who received placebo, for a difference of 47 percentage points (95% confidence interval [CI], 32 to 57; P<0.001). The alkaline phosphatase level normalized in 15% of the patients in the elafibranor group and in none of the patients in the placebo group at week 52 (difference, 15 percentage points; 95% CI, 6 to 23; P = 0.002). Among patients who had moderate-to-severe pruritus (44 patients in the elafibranor group and 22 in the placebo group), the least-squares mean change from baseline through week 52 on the WI-NRS did not differ significantly between the groups (-1.93 vs. -1.15; difference, -0.78; 95% CI, -1.99 to 0.42; P = 0.20). Adverse events that occurred more frequently with elafibranor than with placebo included abdominal pain, diarrhea, nausea, and vomiting. CONCLUSIONS: Treatment with elafibranor resulted in significantly greater improvements in relevant biochemical indicators of cholestasis than placebo. (Funded by GENFIT and Ipsen; ELATIVE ClinicalTrials.gov number, NCT04526665.).
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Chalconas , Fármacos Gastrointestinais , Cirrose Hepática Biliar , Receptores Ativados por Proliferador de Peroxissomo , Propionatos , Humanos , Administração Oral , Fosfatase Alcalina/sangue , Bilirrubina/sangue , Chalconas/administração & dosagem , Chalconas/efeitos adversos , Chalconas/uso terapêutico , Colestase/sangue , Colestase/tratamento farmacológico , Colestase/etiologia , Método Duplo-Cego , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/tratamento farmacológico , Receptores Ativados por Proliferador de Peroxissomo/agonistas , PPAR alfa/agonistas , PPAR delta/agonistas , Propionatos/administração & dosagem , Propionatos/efeitos adversos , Propionatos/uso terapêutico , Prurido/tratamento farmacológico , Prurido/etiologia , Resultado do Tratamento , Ácido Ursodesoxicólico/efeitos adversos , Ácido Ursodesoxicólico/uso terapêutico , Colagogos e Coleréticos/administração & dosagem , Colagogos e Coleréticos/efeitos adversos , Colagogos e Coleréticos/uso terapêuticoRESUMO
The quantum spin properties of nitrogen-vacancy defects in diamond enable diverse applications in quantum computing and communications1. However, fluorescent nanodiamonds also have attractive properties for in vitro biosensing, including brightness2, low cost3 and selective manipulation of their emission4. Nanoparticle-based biosensors are essential for the early detection of disease, but they often lack the required sensitivity. Here we investigate fluorescent nanodiamonds as an ultrasensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity5 and frequency-domain analysis6 to separate the signal from background autofluorescence7, which typically limits sensitivity. Focusing on the widely used, low-cost lateral flow format as an exemplar, we achieve a detection limit of 8.2 × 10-19 molar for a biotin-avidin model, 105 times more sensitive than that obtained using gold nanoparticles. Single-copy detection of HIV-1 RNA can be achieved with the addition of a 10-minute isothermal amplification step, and is further demonstrated using a clinical plasma sample with an extraction step. This ultrasensitive quantum diagnostics platform is applicable to numerous diagnostic test formats and diseases, and has the potential to transform early diagnosis of disease for the benefit of patients and populations.
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Técnicas Biossensoriais/métodos , Diagnóstico Precoce , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/genética , Nanodiamantes/química , RNA Viral/sangue , Avidina/química , Técnicas Biossensoriais/instrumentação , Biotina/química , Fluorescência , Ouro/química , HIV-1/isolamento & purificação , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Microfluídica/instrumentação , Microfluídica/métodos , Micro-Ondas , Técnicas de Amplificação de Ácido Nucleico , Papel , Plasma/virologia , Teoria Quântica , Sensibilidade e Especificidade , Imagem Individual de Molécula , TemperaturaRESUMO
Carbon dioxide (CO2) supersaturation in lakes and rivers worldwide is commonly attributed to terrestrial-aquatic transfers of organic and inorganic carbon (C) and subsequent, in situ aerobic respiration. Methane (CH4) production and oxidation also contribute CO2 to freshwaters, yet this remains largely unquantified. Flood pulse lakes and rivers in the tropics are hypothesized to receive large inputs of dissolved CO2 and CH4 from floodplains characterized by hypoxia and reducing conditions. We measured stable C isotopes of CO2 and CH4, aerobic respiration, and CH4 production and oxidation during two flood stages in Tonle Sap Lake (Cambodia) to determine whether dissolved CO2 in this tropical flood pulse ecosystem has a methanogenic origin. Mean CO2 supersaturation of 11,000 ± 9,000 µatm could not be explained by aerobic respiration alone. 13C depletion of dissolved CO2 relative to other sources of organic and inorganic C, together with corresponding 13C enrichment of CH4, suggested extensive CH4 oxidation. A stable isotope-mixing model shows that the oxidation of 13C depleted CH4 to CO2 contributes between 47 and 67% of dissolved CO2 in Tonle Sap Lake. 13C depletion of dissolved CO2 was correlated to independently measured rates of CH4 production and oxidation within the water column and underlying lake sediments. However, mass balance indicates that most of this CH4 production and oxidation occurs elsewhere, within inundated soils and other floodplain habitats. Seasonal inundation of floodplains is a common feature of tropical freshwaters, where high reported CO2 supersaturation and atmospheric emissions may be explained in part by coupled CH4 production and oxidation.
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17α-estradiol (17α-E2) is a naturally occurring nonfeminizing diastereomer of 17ß-estradiol that has life span-extending effects in rodent models. To date, studies of the systemic and tissue-specific benefits of 17α-E2 have largely focused on the liver, brain, and white adipose tissue with far less focus on skeletal muscle. Skeletal muscle has an important role in metabolic and age-related disease. Therefore, this study aimed to determine whether 17α-E2 treatment has positive, tissue-specific effects on skeletal muscle during a high-fat feeding. We hypothesized that male, but not female, mice, would benefit from 17α-E2 treatment during a high-fat diet (HFD) with changes in the mitochondrial proteome to support lipid oxidation and subsequent reductions in diacylglycerol (DAG) and ceramide content. To test this hypothesis, we used a multiomics approach to determine changes in lipotoxic lipid intermediates, metabolites, and proteins related to metabolic homeostasis. Unexpectedly, we found that 17α-E2 had marked, but different, beneficial effects within each sex. In male mice, we show that 17α-E2 alleviates HFD-induced metabolic detriments of skeletal muscle by reducing the accumulation of diacylglycerol (DAG), and inflammatory cytokine levels, and altered the abundance of most of the proteins related to lipolysis and ß-oxidation. Similar to male mice, 17α-E2 treatment reduced fat mass while protecting muscle mass in female mice but had little muscle inflammatory cytokine levels. Although female mice were resistant to HFD-induced changes in DAGs, 17α-E2 treatment induced the upregulation of six DAG species. In female mice, 17α-E2 treatment changed the relative abundance of proteins involved in lipolysis, ß-oxidation, as well as structural and contractile proteins but to a smaller extent than male mice. These data demonstrate the metabolic benefits of 17α-E2 in skeletal muscle of male and female mice and contribute to the growing literature of the use of 17α-E2 for multi tissue health span benefits.NEW & NOTEWORTHY Using a multiomics approach, we show that 17α-E2 alleviates HFD-induced metabolic detriments in skeletal muscle by altering bioactive lipid intermediates, inflammatory cytokines, and the abundance of proteins related to lipolysis and muscle contraction. The positive effects of 17α-E2 in skeletal muscle occur in both sexes but differ in their outcome.
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Dieta Hiperlipídica , Estradiol , Animais , Masculino , Feminino , Camundongos , Estradiol/farmacologia , Estradiol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Diglicerídeos/metabolismo , Citocinas/metabolismo , Músculo Esquelético/metabolismo , Camundongos Endogâmicos C57BLRESUMO
INTRODUCTION: Neuropathic pain (NP) conditions involve lesions to the somatosensory nervous system leading to chronic and debilitating pain. Many patients suffering from NP utilize pharmacological treatments with various drugs that seek to reduce pathologic neuronal states. However, many of these drugs show poor efficacy as well as cause significant adverse effects. Because of this, there is a major need for the development of safer and more efficacious drugs to treat NP. AREAS COVERED: In this review, we analyzed current treatments being developed for a variety of NP conditions. Specifically, we sought drugs in phase II/III clinical trials with indications for NP conditions. Various databases were searched including Google Scholar, PubMed, and clinicaltrials.gov. EXPERT OPINION: All the mentioned targets for treatments of NP seem to be promising alternatives for existing treatments that often possess poor side effect profiles for patients. However, gene therapy potentially offers the unique ability to inject a plasmid containing growth factors leading to nerve growth and repair. Because of this, gene therapy appears to be the most intriguing new treatment for NP.
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Ensaios Clínicos Fase II como Assunto , Neuropatias Diabéticas , Terapia Genética , Neuralgia Pós-Herpética , Neuralgia , Neuralgia do Trigêmeo , Humanos , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/fisiopatologia , Neuralgia/tratamento farmacológico , Neuralgia/terapia , Neuralgia Pós-Herpética/tratamento farmacológico , Terapia Genética/métodos , Animais , Neuralgia do Trigêmeo/tratamento farmacológico , Neuralgia do Trigêmeo/fisiopatologia , Neuralgia do Trigêmeo/terapia , Ensaios Clínicos Fase III como Assunto , Desenvolvimento de MedicamentosRESUMO
OBJECTIVE: To investigate whether preoperative body morphometry analysis can identify patients at risk of parastomal hernia (PH), which is a common complication after radical cystectomy (RC). PATIENTS AND METHODS: All patients who underwent RC between 2010 and 2020 with available cross-sectional imaging preoperatively and at 1 and 2 years postoperatively were included. Skeletal muscle mass and total fat mass (FM) were determined from preoperative axial computed tomography images obtained at the level of the L3 vertebral body using Aquarius Intuition software. Sarcopenia and obesity were assigned based on consensus definitions of skeletal muscle index (SMI) and FM index (FMI). PH were graded using both the Moreno-Matias and European Hernia Society criteria. Binary logistic regression and recursive partitioning were used to identify patients at risk of PH. The Kaplan-Meier method with log-rank and Cox proportional hazards models included clinical and image-based parameters to identify predictors of PH-free survival. RESULTS: A total of 367 patients were included in the final analysis, with 159 (43%) developing a PH. When utilising binary logistic regression, high FMI (odds ratio [OR] 1.63, P < 0.001) and low SMI (OR 0.96, P = 0.039) were primary drivers of risk of PH. A simplified model that only relied upon FMI, SMI, and preoperative albumin improved the classification of patients at risk of PH. On Kaplan-Meier analysis, patients who were obese or obese and sarcopenic had significantly worse PH-free survival (P < 0.001). CONCLUSION: Body morphometry analysis identified FMI and SMI to be the most consistent predictors of PH after RC.
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BACKGROUND: Mediumweight (40-60 g/m2) polypropylene (MWPP) mesh has been shown to be safe and effective in CDC class II-III retromuscular ventral hernia repairs (RMVHR). However, MWPP has the potential to fracture, and it is possible that heavyweight (> 75 g/m2) polypropylene mesh has similar outcomes in this context. However, there is limited data on HWPP mesh performance in clean-contaminated and contaminated scenarios. We aimed to compare HWPP to MWPP mesh in CDC class II-III wounds during open RMVHR. METHODS: The Abdominal Core Health Quality Collaborative database was retrospectively queried for a cohort of patients who underwent open RMVHR with MWPP or HWPP mesh placed in CDC class II/III wounds from 2012 to 2023. Mesh types were compared using a 3:1 propensity score-matched analysis. Covariates for matching included CDC classification, BMI, diabetes, smoking within 1 year, hernia, and mesh width. Primary outcome of interest included wound complications. Secondary outcomes included reoperations and readmissions at 30 days. RESULTS: A total of 1496 patients received MWPP or HWPP (1378 vs. 118, respectively) in contaminated RMVHR. After propensity score matching, 351 patients remained in the mediumweight and 117 in the heavyweight mesh group. There were no significant differences in surgical site infection (SSI) rates (13.4% vs. 14.5%, p = 0.877), including deep SSIs (0.3% vs. 0%, p = 1), surgical site occurrence rates (17.9% vs. 22.2%, p = 0.377), surgical site occurrence requiring procedural intervention (16% vs. 17.9%, p = 0.719), mesh removal (0.3% vs. 0%, p = 1), reoperations (4.6% vs. 2.6%, p = 0.428), or readmissions (12.3% vs. 9.4%, p = 0.504) at 30 days. CONCLUSION: HWPP mesh was not associated with increased wound morbidity, mesh excisions, reoperations, or readmissions in the early postoperative period compared with MWPP mesh in open RMVHR for CDC II/III cases. Longer follow-up will be necessary to determine if HWPP mesh may be a suitable alternative to MWPP mesh in contaminated scenarios.
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Hérnia Ventral , Herniorrafia , Polipropilenos , Telas Cirúrgicas , Infecção da Ferida Cirúrgica , Humanos , Hérnia Ventral/cirurgia , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos , Masculino , Feminino , Herniorrafia/métodos , Herniorrafia/efeitos adversos , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Idoso , Resultado do Tratamento , Readmissão do Paciente/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
INTRODUCTION: Intraperitoneal onlay mesh (IPOM) placement for small to medium-sized hernias has garnered negative attention due to perceived long-term risk of mesh-related complications. However, sparse data exists supporting such claims after minimally invasive (MIS) IPOM repairs and most is hindered by the lack of long-term follow-up. We sought to report long-term outcomes and mesh-related complications of MIS IPOM ventral hernia repairs. METHODS AND PROCEDURES: Adult patients who underwent MIS IPOM ventral hernia repair at our institution were identified in the Abdominal Core Health Quality Collaborative database from October 2013 to October 2020. Outcomes included hernia recurrence and mesh-related complications or reoperations up to 6 years postoperatively. RESULTS: A total of 325 patients were identified. The majority (97.2%) of cases were elective, non-recurrent (74.5%), and CDC class I (99.4%). Mean hernia width was 4.16 ± 3.86 cm. Median follow-up was 3.6 (IQR 2.8-5) years. Surgeon-entered or patient-reported follow-up was available for 253 (77.8%) patients at 3 years or greater postoperatively. One patient experienced an early small bowel obstruction and was reoperated on within 30 days. Two-hundred forty-five radiographic examinations were available up to 6 years postoperatively. Twenty-seven patients had hernia recurrence on radiographic examination up to 6 years postoperatively. During long-term follow-up, two mesh-related complications required reoperations: mesh removed for chronic pain and mesh removal at the time of colon surgery for perforated cancer. Sixteen additional patients required reoperation within 6 years for the following reasons: hernia recurrence (n = 5), unrelated intraabdominal pathology (n = 9), obstructed port site hernia (n = 1), and adhesive bowel obstruction unrelated to the prosthesis (n = 1). The rate of reoperation due to intraperitoneal mesh complications was 0.62% (2/325) with up to 6 year follow-up. CONCLUSION: Intraperitoneal mesh for repair of small to medium-sized hernias has an extremely low rate of long-term mesh-related complications. It remains a safe and durable option for hernia surgeons.
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Procedimentos Cirúrgicos do Sistema Digestório , Hérnia Ventral , Hérnia Incisional , Obstrução Intestinal , Laparoscopia , Adulto , Humanos , Telas Cirúrgicas/efeitos adversos , Hérnia Ventral/cirurgia , Herniorrafia/efeitos adversos , Próteses e Implantes , Obstrução Intestinal/cirurgia , Hérnia Incisional/cirurgia , RecidivaRESUMO
INTRODUCTION: Fixation of mesh during minimally invasive inguinal hernia repair is thought to contribute to chronic post-herniorrhaphy groin pain (CGP). In contrast to permanent tacks, absorbable tacks are hypothesized to minimize the likelihood of CGP. This study aimed to compare the rates of CGP after laparoscopic inguinal hernia repair between absorbable versus permanent fixation at maximum follow-up. METHODS: This is a post hoc analysis of a randomized controlled trial in patients undergoing laparoscopic inguinal hernia repair (NCT03835351). All patients were contacted at maximum follow-up after surgery to administer EuraHS quality of life (QoL) surveys. The pain and restriction of activity subdomains of the survey were utilized. The primary outcome was rate of CGP, as defined by a EuraHS QoL pain domain score ≥ 4 measured at ≥ 1 year postoperatively. The secondary outcomes were pain and restriction of activity domain scores and hernia recurrence at maximum follow-up. RESULTS: A total of 338 patients were contacted at a mean follow-up of 28 ± 11 months. 181 patients received permanent tacks and 157 patients received absorbable tacks during their repair. At maximum follow-up, the rates of CGP (27 [15%] vs 28 [18%], P = 0.47), average pain scores (1.78 ± 4.38 vs 2.32 ± 5.40, P = 0.22), restriction of activity scores (1.39 ± 4.32 vs 2.48 ± 7.45, P = 0.18), and the number of patients who reported an inguinal bulge (18 [9.9%] vs 15 [9.5%], P = 0.9) were similar between patients with permanent versus absorbable tacks. On multivariable analysis, there was no significant difference in the odds of CGP between the two groups (OR 1.23, 95% CI [0.60, 2.50]). CONCLUSION: Mesh fixation with permanent tacks does not appear to increase the risk of CGP after laparoscopic inguinal hernia repair when compared to fixation with absorbable tacks. Prospective trials are needed to further evaluate this relationship.
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Implantes Absorvíveis , Dor Crônica , Virilha , Hérnia Inguinal , Herniorrafia , Laparoscopia , Dor Pós-Operatória , Telas Cirúrgicas , Humanos , Hérnia Inguinal/cirurgia , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Herniorrafia/métodos , Herniorrafia/efeitos adversos , Masculino , Dor Pós-Operatória/etiologia , Pessoa de Meia-Idade , Feminino , Virilha/cirurgia , Dor Crônica/etiologia , Idoso , Qualidade de Vida , Seguimentos , AdultoRESUMO
BACKGROUND: The healthcare system plays a pivotal role in environmental sustainability, and the operating room (OR) significantly contributes to its overall carbon footprint. In response to this critical challenge, leading medical societies, government bodies, regulatory agencies, and industry stakeholders are taking measures to address healthcare sustainability and its impact on climate change. Healthcare now represents almost 20% of the US national economy and 8.5% of US carbon emissions. Internationally, healthcare represents 5% of global carbon emissions. US Healthcare is an outlier in both per capita cost, and per capita greenhouse gas emission, with almost twice per capita emissions compared to every other country in the world. METHODS: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and the European Association for Endoscopic Surgery (EAES) established the Sustainability in Surgical Practice joint task force in 2023. This collaborative effort aims to actively promote education, mitigation, and innovation, steering surgical practices toward a more sustainable future. RESULTS: Several key initiatives have included a survey of members' knowledge and awareness, a scoping review of terminology, metrics, and initiatives, and deep engagement of key stakeholders. DISCUSSION: This position paper serves as a Call to Action, proposing a series of actions to catalyze and accelerate the surgical sustainability leadership needed to respond effectively to climate change, and to lead the societal transformation towards health that our times demand.
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Pegada de Carbono , Mudança Climática , Salas Cirúrgicas , Salas Cirúrgicas/organização & administração , Humanos , Estados Unidos , Desenvolvimento SustentávelRESUMO
BACKGROUND: Surgical care in the operating room (OR) contributes one-third of the greenhouse gas (GHG) emissions in healthcare. The European Association of Endoscopic Surgery (EAES) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) initiated a joint Task Force to promote sustainability within minimally invasive gastrointestinal surgery. METHODS: A scoping review was conducted by searching MEDLINE via Ovid, Embase via Elsevier, Cochrane Central Register of Controlled Trials, and Scopus on August 25th, 2023 to identify articles reporting on the impact of gastrointestinal surgical care on the environment. The objectives were to establish the terminology, outcome measures, and scope associated with sustainable surgical practice. Quantitative data were summarized using descriptive statistics. RESULTS: We screened 22,439 articles to identify 85 articles relevant to anesthesia, general surgical practice, and gastrointestinal surgery. There were 58/85 (68.2%) cohort studies and 12/85 (14.1%) Life Cycle Assessment (LCA) studies. The most commonly measured outcomes were kilograms of carbon dioxide equivalents (kg CO2eq), cost of resource consumption in US dollars or euros, surgical waste in kg, water consumption in liters, and energy consumption in kilowatt-hours. Surgical waste production and the use of anesthetic gases were among the largest contributors to the climate impact of surgical practice. Educational initiatives to educate surgical staff on the climate impact of surgery, recycling programs, and strategies to restrict the use of noxious anesthetic gases had the highest impact in reducing the carbon footprint of surgical care. Establishing green teams with multidisciplinary champions is an effective strategy to initiate a sustainability program in gastrointestinal surgery. CONCLUSION: This review establishes standard terminology and outcome measures used to define the environmental footprint of surgical practices. Impactful initiatives to achieve sustainability in surgical practice will require education and multidisciplinary collaborations among key stakeholders including surgeons, researchers, operating room staff, hospital managers, industry partners, and policymakers.
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BACKGROUND: Surgical care significantly contributes to healthcare-associated greenhouse gas emissions (GHG). Surgeon attitudes about mitigation of the impact of surgical practice on environmental sustainability remains poorly understood. To better understand surgeon perspectives globally, the Society of American Gastrointestinal and Endoscopic Surgeons and the European Association for Endoscopic Surgery established a joint Sustainability in Surgical Practice (SSP) Task Force and distributed a survey on sustainability. METHODS: Our survey asked about (1) surgeon attitudes toward sustainability, (2) ability to estimate the carbon footprint of surgical procedures and supplies, (3) concerns about the negative impacts of sustainable interventions, (4) willingness to change specific practices, and (5) preferred educational topics and modalities. Questions were primarily written in Likert-scale format. A clustering analysis was performed to determine whether survey respondents could be grouped into distinct subsets to inform future outreach and education efforts. RESULTS: We received 1024 responses, predominantly from North America and Europe. The study revealed that while 63% of respondents were motivated to enhance the sustainability of their practice, less than 10% could accurately estimate the carbon footprint of surgical activities. Most were not concerned that sustainability efforts would negatively impact their practice and showed readiness to adopt proposed sustainable practices. Online webinars and modules were the preferred educational methods. A clustering analysis identified a group particularly concerned yet willing to adopt sustainable changes. CONCLUSION: Surgeons believe that operating room waste is a critical issue and are willing to change practice to improve it. However, there exists a gap in understanding the environmental impact of surgical procedures and supplies, and a sizable minority have some degree of concern about potential adverse consequences of implementing sustainable policies. This study uniquely provides an international, multidisciplinary snapshot of surgeons' attitudes, knowledge, concerns, willingness, and preferred educational modalities related to mitigating the environmental impact of surgical practice.
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PURPOSE OF REVIEW: Patients often experience a significant degree of knee pain following total knee replacement (TKR). To alleviate this pain, nerve blocks may be performed such as the adductor canal block (ACB). However, ACBs are unable to relieve pain originating from the posterior region of the knee. A new type of nerve block known as the IPACK block may be used in conjunction with ACBs as it is designed to inhibit nerve branches innervating this area. In this article, we examine the rationale behind the IPACK procedure, how it is performed, and clinical trials examining its efficacy. RECENT FINDINGS: 5 of the 7 clinical trials examined in this article showed the IPACK + ACB block to show superior efficacy in treating pain following TKR compared to other blocks. These blocks included PMDI+ACB, SPANK+ACB, PAI+ACB, ACB alone, and SCAB. 2 of the 7 clinical trials showed the IPACK + ACB to be less effective in managing patients pain following TKR compared to other blocks which included the CACB and 4 in 1 block. In most instances, the IPACK + ACB showed superior efficacy in managing patients' pain following TKR when compared to other types of nerve blocks. This was determined by measuring usage of opioids, reported postoperative pain, and length of hospital stays following TKR. Thus, we suppose the IPACK block may be used in conjunction with the ACB to effectively reduce patient's pain following TKR.
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Artroplastia do Joelho , Bloqueio Nervoso , Manejo da Dor , Dor Pós-Operatória , Humanos , Artroplastia do Joelho/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Manejo da Dor/métodos , Dor Aguda/tratamento farmacológico , Dor Aguda/etiologia , Resultado do TratamentoRESUMO
INTRODUCTION: As hospitals strive to reduce their environmental footprint, there is an ongoing debate over the environmental implications of reusable versus disposable linens in operating rooms (ORs). This research aimed to compare the environmental impact of reusable versus single-use OR bed covers and lift sheets using life cycle assessment (LCA) methodology. METHODS: LCA is an established tool with rigorous methodology that uses science-based processes to measure environmental impact. This study compared the impacts of three independent system scenarios at a single large academic hospital: reusable bed covers with 50 laundry cycles and subsequent landfill disposal (System 1), single-use bed covers with waste landfill disposal (System 2), and single-use bed covers with waste disposal using incineration (System 3). RESULTS: The total carbon footprint of System 1 for 50 uses was 19.83 âkg carbon dioxide equivalents (CO2-eq). System 2 generated 64.99 âkg CO2-eq. For System 3, the total carbon footprint was 108.98 âkg CO2-eq. The raw material extraction for all the material to produce an equivalent 50 single-use OR bed cover kits was tenfold more carbon-intensive than the reusable bed cover. Laundering one reusable OR bed cover 50 times was more carbon intensive (12.12 âkg CO2-eq) than landfill disposal of 50 single-use OR bed covers (2.52 âkg CO2-eq). DISCUSSION: Our analysis demonstrates that one reusable fabric-based OR bed cover laundered 50 times, despite the carbon and water-intensive laundering process, exhibits a markedly lower carbon footprint than its single-use counterparts. The net difference is 45.16 âkg CO2-eq, equivalent to driving 115 miles in an average gasoline-powered passenger vehicle. This stark contrast underscores the efficacy of adopting reusable solutions to mitigate environmental impact within healthcare facilities.
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Pegada de Carbono , Reutilização de Equipamento , Salas Cirúrgicas , Humanos , Roupas de Cama, Mesa e Banho , Equipamentos Descartáveis , Meio Ambiente , ReciclagemRESUMO
Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 µV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.
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Fibrilação Atrial , Cardiopatias , AVC Isquêmico , Pirazóis , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Método Duplo-Cego , Canadá , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações , Aspirina/efeitos adversos , Piridonas/efeitos adversos , Piridonas/administração & dosagem , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Cardiopatias/complicações , AVC Isquêmico/tratamento farmacológico , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Hemorragias Intracranianas/induzido quimicamenteRESUMO
Protein-protein interactions are fundamental to life processes. Complementary computational, structural, and biophysical studies of these interactions enable the forces behind their specificity and strength to be understood. Antibody fragments such as single-chain antibodies have the specificity and affinity of full antibodies but a fraction of their size, expediting whole molecule studies and distal effects without exceeding the computational capacity of modeling systems. We previously reported the crystal structure of a high-affinity nanobody 59H10 bound to HIV-1 capsid protein p24 and deduced key interactions using all-atom molecular dynamics simulations. We studied the properties of closely related medium (37E7) and low (48G11) affinity nanobodies, to understand how changes of three (37E7) or one (48G11) amino acids impacted these interactions; however, the contributions of enthalpy and entropy were not quantified. Here, we report the use of qualitative and quantitative experimental and in silico approaches to separate the contributions of enthalpy and entropy. We used complementary circular dichroism spectroscopy and molecular dynamics simulations to qualitatively delineate changes between nanobodies in isolation and complexed with p24. Using quantitative techniques such as isothermal titration calorimetry alongside WaterMap and Free Energy Perturbation protocols, we found the difference between high (59H10) and medium (37E7) affinity nanobodies on binding to HIV-1 p24 is entropically driven, accounted for by the release of unstable waters from the hydrophobic surface of 59H10. Our results provide an exemplar of the utility of parallel in vitro and in silico studies and highlight that differences in entropic interactions between amino acids and water molecules are sufficient to drive orders of magnitude differences in affinity.
Assuntos
Infecções por HIV , Anticorpos de Domínio Único , Humanos , Termodinâmica , Entropia , Aminoácidos/metabolismo , Ligação Proteica , CalorimetriaRESUMO
Estrogen signaling is protective against chronic liver diseases, although men and a subset of women are contraindicated for chronic treatment with 17ß-estradiol (17ß-E2) or combination hormone replacement therapies. We sought to determine if 17α-estradiol (17α-E2), a naturally occurring diastereomer of 17ß-E2, could attenuate liver fibrosis. We evaluated the effects of 17α-E2 treatment on collagen synthesis and degradation rates using tracer-based labeling approaches in male mice subjected to carbon tetrachloride (CCl4)-induced liver fibrosis. We also assessed the effects of 17α-E2 on markers of hepatic stellate cell (HSC) activation, collagen cross-linking, collagen degradation, and liver macrophage content and polarity. We found that 17α-E2 significantly reduced collagen synthesis rates and increased collagen degradation rates, which was mirrored by declines in transforming growth factor ß1 (TGF-ß1) and lysyl oxidase-like 2 (LOXL2) protein content in liver. These improvements were associated with increased matrix metalloproteinase 2 (MMP2) activity and suppressed stearoyl-coenzyme A desaturase 1 (SCD1) protein levels, the latter of which has been linked to the resolution of liver fibrosis. We also found that 17α-E2 increased liver fetuin-A protein, a strong inhibitor of TGF-ß1 signaling, and reduced proinflammatory macrophage activation and cytokines expression in the liver. We conclude that 17α-E2 reduces fibrotic burden by suppressing HSC activation and enhancing collagen degradation mechanisms. Future studies will be needed to determine if 17α-E2 acts directly in hepatocytes, HSCs, and/or immune cells to elicit these benefits.
Assuntos
Metaloproteinase 2 da Matriz , Fator de Crescimento Transformador beta1 , Masculino , Camundongos , Feminino , Animais , Fator de Crescimento Transformador beta1/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Estradiol/farmacologia , Estradiol/metabolismo , Longevidade , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Fígado/metabolismo , Colágeno/metabolismoRESUMO
Structurally coloured materials that change their colour in response to mechanical stimuli are uniquely suited for optical sensing and visual communication1-4. The main barrier to their widespread adoption is a lack of manufacturing techniques that offer spatial control of the materials' nanoscale structures across macroscale areas. Here, by adapting Lippmann photography5, we report an approach for producing large-area, structurally coloured sheets with a rich and easily controlled design space of colour patterns, spectral properties, angular scattering characteristics and responses to mechanical stimuli. Relying on just a digital projector and commercially available photosensitive elastomers, our approach is fast, scalable, affordable and relevant for a wide range of manufacturing settings. We also demonstrate prototypes for mechanosensitive healthcare materials and colorimetric strain and stress sensing for human-computer interaction and robotics.
Assuntos
Elastômeros , Robótica , Cor , Elastômeros/química , HumanosRESUMO
BACKGROUND: Regional lymph node metastasis (RLNM) occurs infrequently in patients with soft tissue sarcoma (STS), although certain STS subtypes have a higher propensity for RLNM. The identification of RLNM has significant implications for staging and prognosis; however, the precise impact of node-positive disease on patient survival remains a topic of controversy. Although the benefits of sentinel lymph node biopsy (SLNB) are well documented in patients with melanoma and breast cancer, whether this procedure offers a benefit in STS is controversial. METHODS: A systematic literature search was performed and articles reviewed to determine if SLNB in patients with extremity/truncal STS impacts disease-free or overall survival. RESULTS: Six studies were included. Rates of sentinel lymph node positivity were heterogeneous (range 4.3-50%). The impact of SLNB on patient outcomes remains unclear. The overall quality of available evidence was low, as assessed by the Grading of Recommendations, Assessment, Development, and Evaluation system. CONCLUSIONS: The literature addressing the impact of nodal basin evaluation on the staging and management of patients with extremity/truncal STS is confounded by heterogeneous patient cohorts and clinical practices. Multicenter prospective studies are warranted to determine the true incidence of RLNM and whether SLNB could benefit patients with clinically occult RLNM at diagnosis.
Assuntos
Sarcoma , Linfonodo Sentinela , Neoplasias Cutâneas , Neoplasias de Tecidos Moles , Humanos , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Estadiamento de Neoplasias , Sarcoma/cirurgia , Sarcoma/patologia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias de Tecidos Moles/patologia , Extremidades/cirurgia , Extremidades/patologia , Linfonodo Sentinela/patologia , Linfonodos/patologia , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Injuries during initial port placement in minimally invasive abdominal surgery are rare but can cause major morbidity. We aimed to characterize the incidence, consequence, and risk factors for injury occurring on initial port placement. METHODS: This is a retrospective review of a General Surgery quality collaborative database with supplementary input from the Morbidity and Mortality conference database at our institution between 6/25/2018 and 6/30/2022. Patient characteristics, operative details, and postoperative course were assessed. Cases with an injury on entry were compared to cases without an injury to identify risk factors for injury. RESULTS: 8844 minimally invasive cases were present between the two databases. Thirty-four injuries (0.38%) occurred during initial port placement. Seventy-one percent of injuries were bowel injuries (full or partial thickness) and the majority (79%) of injuries were recognized during the index operation. Median surgeon experience for the cases with an injury was 9 years (IQR 4.25-14.5) compared to 12 years of experience for all surgeons contributing to the database (p = 0.004). Previous laparotomy was also significantly correlated with the rate of injury on entry (p = 0.012). There was no significant difference in the rate of injury based on method of entry (cut-down: 19 (55.9%), optical entry without Veress: 10 (29.4%), Veress followed by optical entry: 5 (14.7%), p = 0.11). BMI > 30 kg/m2 (injury: 16/34 vs no injury: 2538/8844, p = 0.847) was not associated with an injury. Fifty-six percent (19/34) of patients with an injury on initial port placement required laparotomy at some point in their hospital course. CONCLUSIONS: Injuries are rare during initial port placement for minimally invasive abdominal surgery. In our database, history of a previous laparotomy was a significant risk factor for an injury and appears to be more consequential than commonly implicated factors such as technique, patient body habitus, or surgeon experience.