RESUMO
INTRODUCTION: The aim of this study was to assess the safety of bronchoscopic microwave ablation (MWA) of peripheral lung parenchyma using the NEUWAVE™ FLEX Microwave Ablation System, and robotic-assisted bronchoscopy (RAB) using the MONARCH™ Platform in a swine model. METHODS: Computed tomography (CT)-guided RAB MWA was performed in the peripheral lung parenchyma of 17 Yorkshire swine (40-50 kg) and procedural adverse events (AEs) documented. The acute group (day 0, n = 5) received 4 MWAs at 100 W for 1, 3, 5, and 10 min in 4 different lung lobes. Subacute and chronic groups (days 3 and 30, n = 6 each) received one MWA (100 W, 10 min) per animal. RESULTS: The study was completed without major procedural complications. No postprocedural AEs including death, pneumothorax, bronchopleural fistula, hemothorax, or pleural effusions were observed. No gross or histological findings suggestive of thromboembolism were found in any organ. One 3-Day and one 30-Day swine exhibited coughing that required no medication (minor AEs), and one 30-Day animal required antibiotic medication (major AE) for a suspected lower respiratory tract infection that subsided after two weeks. CT-based volumetric estimates of ablation zones in the acute group increased in an ablation time-dependent (1-10 min) manner, whereas macroscopy-based estimates showed an increasing trend in ablation zone size. CONCLUSION: The NEUWAVE FLEX and MONARCH devices were safely used to perform single or multiple RAB MWAs. The preclinical procedural safety profile of RAB MWA supports clinical research of both devices to investigate efficacy in select patients with oligometastatic disease or primary NSCLC.
Assuntos
Ablação por Cateter , Neoplasias Pulmonares , Procedimentos Cirúrgicos Robóticos , Animais , Suínos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Broncoscopia , Micro-Ondas/uso terapêutico , Segurança de Equipamentos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Pulmão/patologia , Neoplasias Pulmonares/cirurgia , Ablação por Cateter/métodosRESUMO
Management of pain in the treatment of rheumatoid arthritis (RA) is a priority that is not fully addressed by the conventional therapies. In the present study, we evaluated the efficacy of cannabinoid receptor 2 (CB2) agonist JWH-015 using RA synovial fibroblasts (RASFs) obtained from patients diagnosed with RA and in a rat adjuvant-induced arthritis (AIA) model of RA. Pretreatment of human RASFs with JWH-015 (10-20 µM) markedly inhibited the ability of pro-inflammatory cytokine interleukin-1ß (IL-1ß) to induce production of IL-6 and IL-8 and cellular expression of inflammatory cyclooxygenase-2 (COX-2). JWH-015 was effective in reducing IL-1ß-induced phosphorylation of TAK1 (Thr184/187) and JNK/SAPK in human RASFs. While the knockdown of CB2 in RASFs using siRNA method reduced IL-1ß-induced inflammation, JWH-015 was still effective in eliciting its anti-inflammatory effects despite the absence of CB2, suggesting the role of non-canonical or an off-target receptor. Computational studies using molecular docking and molecular dynamics simulations showed that JWH-105 favorably binds to glucocorticoid receptor (GR) with the binding pose and interactions similar to its well-known ligand dexamethasone. Furthermore, knockdown of GR using siRNA abrogated JWH-015's ability to reduce IL-1ß-induced IL-6 and IL-8 production. In vivo, administration of JWH-015 (5 mg/kg, daily i.p. for 7 days at the onset of arthritis) significantly ameliorated AIA in rats. Pain assessment studies using von Frey method showed a marked antinociception in AIA rats treated with JWH-015. In addition, JWH-015 treatment inhibited bone destruction as evident from micro-CT scanning and bone analysis on the harvested joints and modulated serum RANKL and OPG levels. Overall, our findings suggest that CB2 agonist JWH-015 elicits anti-inflammatory effects partly through GR. This compound could further be tested as an adjunct therapy for the management of pain and tissue destruction as a non-opioid for RA.
Assuntos
Artrite Experimental/tratamento farmacológico , Fibroblastos/imunologia , Indóis/farmacologia , Interleucina-1beta/imunologia , Receptor CB2 de Canabinoide/agonistas , Receptores de Esteroides/imunologia , Membrana Sinovial/imunologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Artrite Experimental/patologia , Feminino , Fibroblastos/patologia , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Ratos , Ratos Endogâmicos Lew , Receptor CB2 de Canabinoide/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Membrana Sinovial/patologiaRESUMO
BACKGROUND: Local anesthesia is an important skill and a prerequisite for most dental treatments. However, the step from theory to application on the patient is huge for the novice. Hence, a mannequin training model course was developed and implemented into the existing local anesthesia curriculum in undergraduate dental students. It was the aim of this study to evaluate the relation between training-model and real-life anesthesia performance and to measure whether a gain in skill on the model translates to the actual patient situation. METHODS: Thirty-six third-year students (14 males, 22 females, age 24 years±2.98) attended the four-day course comprising each 4 h of lectures and practical training. The student cohort gave subjective ratings about the didactical components of the course after attendance by using the TRIL questionnaire (TRIL-mod; University of Trier). At the end of the course the performance of each student in administering an inferior alveolar nerve (IAN) block on the training model as well as on a fellow dental student was investigated using a standardized checklist. To evaluate the successful performance, the in vivo IAN-block was assessed using subjective patient-feeling, the sharp-blunt test and an objective pain- and thermal sensitivity tester (PATH). RESULTS: The course was rated with an average score of 5.25 ± 0.44 (range 1-6; 6 = best). On the training model, 69.4% of the students successfully performed an IAN-block. The in vivo assessment, objectified by the PATH test, showed a successful anesthesia in 36.9% of the cases. The assessment of local anesthesia by using the sharp blunt test and the subjective patient feeling significantly correlated with these findings (k = 0.453-0.751, p < 0.05). The model performance did not correlate with the performance on the patient (k = 0.137, p = 0.198). CONCLUSIONS: Although subjective ratings of the course were high, the anesthesia success rate on mannequin models did not imply an equal performance on the in vivo setting. As local anesthesia training models are a valuable didactic complement, the focus of the training should be on to the actual real life situation. Chair side feedback should be offered to the students using one of the presented evaluation methods.
Assuntos
Anestesia Dentária/métodos , Anestesia Local/métodos , Anestesiologia/educação , Competência Clínica/normas , Educação em Odontologia , Estudantes de Odontologia , Pontos de Referência Anatômicos , Atitude do Pessoal de Saúde , Estudos de Coortes , Currículo , Feminino , Humanos , Injeções , Masculino , Manequins , Inquéritos e Questionários , Ensino , Adulto JovemRESUMO
Fibrin Pad is a hemostatic pad designed to control surgical-related bleeding. It consists of a fully absorbable composite matrix scaffold coated with human-derived active biologics that immediately form a fibrin clot upon contact with targeted bleeding surfaces. Studies were conducted to investigate the effect of Fibrin Pad and its biologics-free composite matrix component (Matrix) on the wound healing process in in vitro and in vivo models. Fibrin Pad was evaluated in solid organ, soft tissue defects, and subcutaneous tissues. Immunocompromised rodents were used to avoid xeno-mediated responses. Extracts created from both materials were evaluated for biological activity using in vitro cell culture assays. Neither Fibrin Pad nor Matrix alone showed any inhibition of the wound healing of treated defect sites. An apparent accelerated healing was noted in the soft tissue and subcutaneous tissue defects with Fibrin Pad as compared to Matrix. Both materials showed desirable properties associated with tissue scaffolds. The in vitro study results show that Fibrin Pad extract can induce dose-dependent increases in fibroblast proliferation and migration. These studies confirm that the biologic components of Fibrin Pad can enhance wound healing processes in in vitro assays and fully support wound healing at the site of in vivo application.
Assuntos
Fibrina/farmacologia , Hemostáticos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Nádegas/patologia , Proliferação de Células/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Humanos , Imuno-Histoquímica , Implantes Experimentais , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos SCID , Músculos/efeitos dos fármacos , Músculos/patologia , Ratos , Ratos Nus , Tela Subcutânea/irrigação sanguínea , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/patologiaRESUMO
BACKGROUND: Watertight repair of the dura is imperative after neurosurgical procedures involving the brain or spinal cord because inadequately treated leakage of cerebrospinal fluid (CSF) from punctured dura can have serious consequences such as meningitis, arachnoiditis, or epidural abscess. OBJECTIVE: To assess the efficacy of Evicel Fibrin Sealant (Human) to prevent CSF leakage using a 2.0-cm durotomy mongrel dog repair model and to compare the tissue response with Tisseel (a fibrin sealant) and Duraseal (a synthetic polyethylene glycol [PEG] hydrogel sealant). METHODS: The canine durotomy repair model was used. This well-characterized model assesses the ability of sealants to achieve intraoperative watertight seals of the dura mater, as well as long-term safety and efficacy. This study included 27 mongrel dogs and had a 28-day duration. RESULTS: The 3 sealants were 100% effective in preventing CSF leakage intraoperatively at 15 mm Hg. The 2 fibrin sealants were 100% effective in postoperative sealing; the PEG hydrogel was not. Microscopically, the tissue changes induced by Evicel at the durotomy site were similar in nature except for foamy macrophages seen only with the PEG hydrogel. The extent and severity of adhesions at 28 days were less with the fibrin sealants than with the PEG hydrogel. CONCLUSION: Evicel, a fibrin sealant, was safe and effective in achieving and maintaining a watertight seal of the dura. The performance of the fibrin sealants was similar to that of the synthetic PEG hydrogel sealant with the exception of a Duraseal seal, which leaked.
Assuntos
Rinorreia de Líquido Cefalorraquidiano/prevenção & controle , Craniotomia/métodos , Dura-Máter/cirurgia , Adesivo Tecidual de Fibrina/farmacologia , Fibrina/uso terapêutico , Animais , Vazamento de Líquido Cefalorraquidiano , Modelos Animais de Doenças , Cães , Masculino , Aderências Teciduais/prevenção & controle , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND: Current management of severe surgical or traumatic bleeding is often achieved by manual tamponade or occlusion using devices such as tourniquets or ligatures. There are some clinical scenarios where these options are either marginally effective or impractical. The present study evaluates a new combination device (Fibrin pad) consisting of biologically active components (human thrombin and fibrinogen) delivered to the targeted site by an absorbable synthetic matrix (oxidized regenerated cellulose and polyglactin 910) in a swine severe bleeding model. In this model, severe bleeding can be managed by concurrent use of several currently available treatments, or a more convenient option that offers performance and safety advantages. MATERIALS AND METHODS: Partial nephrectomies were performed on swine and treated with either Fibrin pad (FP) or conventional therapy (CTR)-temporary occlusion of renal artery, electrocautery, SURGIFLO, EVITHROM, SURGICEL NU-KNIT, and PDS II suture). After intraoperative hemostasis was confirmed, the animals were closed and recovered, then survived for 2, 14, or 56 d. RESULTS: Hemostasis was achieved at surgery and maintained in all FP and CTR treated animals. FP was as effective as CTR at establishing durable hemostasis. Treatment with FP did not require temporary occlusion of the renal artery and decreased the total treatment time by half. No animals in either group had complications related to postoperative bleeding at any time during the study. There was no evidence of pulmonary thrombi or evidence of thrombotic complications. No biologically significant adverse local tissue response was present in association with the Fibrin pad at any study interval, and no biologically relevant or consistent changes in blood parameters were identified. CONCLUSIONS: Fibrin pad was as effective as CTR for the primary management of severe bleeding without occlusion of the renal artery and a shorter surgical time. No evidence of a systemic or local adverse response was identified due to exposure to the Fibrin pad.
Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Hemostasia Cirúrgica/métodos , Hemostáticos/uso terapêutico , Nefrectomia , Hemorragia Pós-Operatória/prevenção & controle , Animais , Feminino , Adesivo Tecidual de Fibrina/efeitos adversos , Adesivo Tecidual de Fibrina/farmacologia , Hemostasia/efeitos dos fármacos , Hemostáticos/efeitos adversos , Hemostáticos/farmacologia , Rim/patologia , Rim/cirurgia , Imageamento por Ressonância Magnética , Modelos Animais , Suínos , Resultado do TratamentoRESUMO
Many surgical methods and hemostatic agents can be used to achieve and maintain hemostasis in surgical fields. Numerous clinical situations exist where current treatment modalities are neither effective nor practical. Assessment of new hemostats primarily targets efficacy. However, the biocompatibility and healing properties associated with hemostats are crucial for regulatory approval and product acceptance. Standard biocompatibility and healing studies may not be appropriate for hemostats containing active biologics. Liver defects in NTac:NIH-Whn (athymic) and Sprague Dawley Outbred (immunocompetent) rats were treated with Fibrin Pad (absorbable matrix containing human-derived biologics) or the matrix only. Defects were evaluated at 14 and 28 days post-implantation. As expected, Fibrin Pad in immunocompetent rats induced a cellular immune response. Unexpectedly, biologically significant decreases in healing, material absorption, and local fibrin degradation were also present. Evaluation of Fibrin Pad in immunocompetent animal models must consider potentially significant alterations in healing, material absorption, and local fibrin degradation, in addition to the expected immune response; none of which may be relevant when Fibrin Pad is used in the clinical setting. These considerations are essential when standard efficacy and biocompatibility studies assessing Fibrin Pad are submitted for regulatory consideration or utilized as pre-clinical translational studies.