Preclinical Experience Research Articles

Assessing the Impact of a Preclinical Immersion on Nurse Practitioner Student Confidence for the Initial Clinical Experience.

It is important for faculty to prepare nurse practitioner students for their first clinical experiences to ensure student success. The purpose of this project was to implement a preclinical immersion and determine student perceptions about this experience. A half-day preclinical immersion was instituted at the beginning of the family nurse practitioner students' first clinical course. Demographic information and survey data were obtained before the preclinical immersion experience, after completion of the immersion experience, and during the last 2 weeks of the first clinical course. Students' ratings of their clinical skills and knowledge improved during the duration of the semester for 5 of the 7 items. Directed content analysis revealed 3 themes: understanding of clinical expectations, face-to-face interactions with faculty, and cognitive/emotional clinical perceptions. The use of preclinical immersion experiences may both practically and emotionally prepare students for graduate nursing clinical experiences.

GREASE II. A phase II randomized, 12-month, parallel-group, superiority study to evaluate the efficacy of a Modified Atkins Diet in Autosomal Dominant Polycystic Kidney Disease patients

IntroductionAutosomal Dominant Polycystic Kidney Disease (ADPKD) is a condition that causes progressive renal function decline. Preclinical data suggest the presence of a profound metabolic derangement in ADPKD. Cystic cells shift their energy metabolism from oxidative phosphorylation to aerobic glycolysis, show inhibition of fatty acid oxidation and become glutamine and arginine dependent. Recent preclinical experiences have suggested beneficial effect in terms of reduction of cystic size, interstitial fibrosis and disease progression, targeting these deregulated metabolic pathways by ketosis induction. The dietetic approach to ADPKD, because of low cost and absence of toxicity, represents an interesting therapeutic strategy. Methods and analysisThe protocol describes a phase II clinical trial that will evaluate the effect on Total Kidney Volume, safety and tolerability of a ketogenic diet in a selected ADPKD population. The trial will have, as secondary objective, the evaluation of the ability of the ketogenic diet to slow down the renal function decline. This will be a 12-month randomized, parallel group, two arm, superiority trial with 1:1 allocation to evaluate the efficacy of a Modified Atkins Diet protocol compared to a balanced normocaloric diet on 90 ADPKD patients. DisseminationThe study results will be released to the patients and the medical community.

Management of Drug Resistance in Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is a rare but aggressive B-cell hemopathy characterized by the translocation t(11;14)(q13;q32) that leads to the overexpression of the cell cycle regulatory protein cyclin D1. This translocation is the initial event of the lymphomagenesis, but tumor cells can acquire additional alterations allowing the progression of the disease with a more aggressive phenotype and a tight dependency on microenvironment signaling. To date, the chemotherapeutic-based standard care is largely inefficient and despite the recent advent of different targeted therapies including proteasome inhibitors, immunomodulatory drugs, tyrosine kinase inhibitors, relapses are frequent and are generally related to a dismal prognosis. As a result, MCL remains an incurable disease. In this review, we will present the molecular mechanisms of drug resistance learned from both preclinical and clinical experiences in MCL, detailing the main tumor intrinsic processes and signaling pathways associated to therapeutic drug escape. We will also discuss the possibility to counteract the acquisition of drug refractoriness through the design of more efficient strategies, with an emphasis on the most recent combination approaches.

Optimized lactoferrin as a highly promising treatment for intracerebral hemorrhage: Pre-clinical experience

Intracerebral hemorrhage (ICH) is the deadliest form of stroke for which there is no effective treatment, despite an endless number of pre-clinical studies and clinical trials. The obvious therapeutic target is the neutralization of toxic products of red blood cell (RBC) lysis that lead to cytotoxicity, inflammation, and oxidative damage. We used rigorous approaches and translationally relevant experimental ICH models to show that lactoferrin-(LTF)-based monotherapy is uniquely robust in reducing brain damage after ICH. Specifically, we designed, produced, and pharmacokinetically/toxicologically characterized an optimized LTF, a fusion of human LTF and the Fc domain of human IgG (FcLTF) that has a 5.8-fold longer half-life in the circulation than native LTF. Following dose-optimization studies, we showed that FcLTF reduces neurological injury caused by ICH in aged male/female mice, and in young male Sprague Dawley (SD) and spontaneously hypertensive rats (SHR). FcLTF showed a remarkably long 24-h therapeutic window. In tissue culture systems, FcLTF protected neurons from the toxic effects of RBCs and promoted microglia toward phagocytosis of RBCs and dead neurons, documenting its pleotropic effect. Our findings indicate that FcLTF is safe and effective in reducing ICH-induced damage in animal models used in this study.

A qualitative analysis of the coping reservoir model of pre-clinical medical student well-being: human connection as making it \u2018worth it\u2019

BackgroundBy all indications, well-being among physicians is poor, which manifests in various outcomes, including burnout, depression/anxiety, low life satisfaction, alcohol/substance misuse, suicide ideation, and suicide. Despite the vast literature on physician burnout, there is relatively little research on how pre-clinical experiences in medical school may be an antecedent to subsequent poor health among physicians. Here we focus on two neglected areas within the literature by focusing on the pre-clinical stage of medical school and the positive, as opposed to exclusively the negative, aspects of the medical school experience as it affects well-being.MethodsThis study utilizes the metaphor of the Coping Reservoir Model as a theoretical and analytical framework for understanding medical student well-being by identify the ‘depleting’ and ‘replenishing’ inputs that are deposited into students’ coping reservoirs. We analyze 105 medical students’ reflective writings using a data analytic process consistent with an interpretive description approach, engaging in a hierarchical 3-step coding process to identify the main replenishing inputs deposited into students’ coping reservoirs.ResultsThe main depleting inputs that we identify are consistent with those identified by The Coping Reservoir Model. In addressing our main research question regarding the replenishing inputs, results show the main positive factors are psycho-social resources, intellectual stimulation, and social support/relationships. Most importantly, relationships with patients shape all three of these positive factors and provide the main source of hope that the stress of medical school will get better.ConclusionsWhat allows students to frame their experiences with hope and optimism are the connections they form with each other and with patients. The prolonged stress of medical school is made “worth it” in hopes that it will “get better” with more meaningful patient interaction in the future. These results that emphasize the positive aspects of medical school are discussed in context of their theoretical contributions to The Coping Reservoir Model and the practical implications for medical education to improve medical student well-being by facilitating human connection.

Reader response: Characteristics of graduating US allopathic medical students pursuing a career in neurology.

The article by Gutmann et al.1 provided an excellent overview of factors in transitioning allopathic medical students into clinical neurology careers. The authors addressed a major issue in neurology as the burden of neurologic disease increases across the world. Subjective assessment of preclinical and clinical neuroscience positive experiences and effective teaching by residents and faculty were unsurprising in their associations with increased rates of retention. However, these findings have been reported in many other medical specialties.2–4

The Student Navigator Project (SNaP): Preparing Students Through Longitudinal Learning.

Early medical school education has historically focused on teaching basic medical sciences. More recently, medical schools are encouraged to incorporate health systems science (HSS) into early curricula. Addressing all of these components in an overcrowded curriculum remains challenging. We report on the Student Navigator Project (SNaP), a pre-clinical experience where students engage longitudinally with medically and socially complex patients. SNaP is built on a foundation of trust, responsibility, and ownership in the student-patient relationship. Early learners take an active role in navigating, advocating, and coaching for their patients. In addition, students are integrated as medical assistants into a primary care clinic; complete a mentored, team-based quality improvement project; and engage in evidence-based medicine, teaching, and handoff activities. As a result of these activities, students learn firsthand about HSS, contribute meaningfully to their patients' care, and are immersed in a systems-based practice approach early in their medical school education. Preliminary outcomes (2016-2019) show satisfaction with the program and knowledge of program focus areas. The authors are engaged in improvement cycles to modify program structure and curriculum in order to promote dissemination in diverse clinical settings. Ultimately, we plan to measure longer-term outcomes, including clerkship and residency preparation, career choice, and practice setting.

Prediction of Survival Benefit of Filgrastim in Adult and Pediatric Patients With Acute Radiation Syndrome

Acute exposure to high doses of radiation leads to severe myelosuppression, but few treatments are currently available to treat hematopoietic syndrome of acute radiation syndrome. Granulocyte colony stimulating factors (e.g., filgrastim) stimulate proliferation of neutrophil precursors and enhance mature neutrophil function. Owing to ethical constraints on conducting clinical research in lethally irradiated humans, we developed a model‐based strategy to integrate preclinical experience in irradiated nonhuman primates (NHPs) and other clinical myelosuppressive conditions to inform filgrastim dosing to treat hematopoietic syndrome of acute radiation syndrome. Models predicting neutrophil counts and overall survival based on drug exposures were calibrated and scaled from NHPs to adult and pediatric human subjects. Several scenarios were examined investigating variations in filgrastim doses, dose frequency, treatment initiation, and duration, as well as the effect of age and radiation dose rate. Model‐based simulations and established safety profiles supported that a subcutaneous filgrastim dose of 10 µg/kg once daily provides a significant survival benefit (50%) over placebo in both adults and children, provided that the treatment is initiated within 1–14 days after radiation exposure and lasts 2–3 weeks. For treatment durations of longer than 3 weeks, filgrastim treatment is not expected to provide significantly greater benefit. This survival benefit is expected to hold for the wide range of radiation doses and dose rates (0.01–1,000 Gy/hours) examined.

"Double-Lumen Valve-Controlled Intra-Operative Pyeloplasty Stent (VIPs)": A New Technology for Post-Pyeloplasty Stenting - Proof of Concept Study in a Preclinical Large Animal Model.

BackgroundPyeloplasty is a common surgical operation with a high success rate. However, significant challenges are to be optimized in the design of stenting systems in order to improve perioperative monitoring of urine drainage and enhance patient and family comfort through easier post-operative care.Materials and MethodsIn a preliminary study in six pigs, handling, mechanical and functional features of this stent system were tested. In our main study, six double-lumen stents (230 mm long each) and 6F/9F external diameter were implanted through the ureteric walls of six domestic pigs to allow postoperative drainage and monitoring following ureteroureterostomy. After a 7-day survival period, monitoring with intravenous antibiotic coverage, and pain control, contrast antegrade pyelogram, under valve control, and renal ultrasonography were conducted and stents explanted and the animals were then euthanized.ResultsThe double-lumen valve-controlled stent supported the healing of the neo anastomoses and helped to monitor perioperative urine drainage and perianastomotic leakage accurately. It also guided a well-controlled more informative radiological contrast-supported imaging before removal of the stents that confirmed the healing of the neo anastomotic site and no leak formation. The double-lumen system demonstrated high feasibility regarding its insertion, functionality, and removal capacities. The excellent flexibility of the individual stents allowed exact anatomically controlled implantation.ConclusionThe double-lumen valve-controlled stent system was studied in a porcine model, which demonstrated its feasibility. Preclinical experience revealed favorable results concerning stent implantation, operability and functionality, in the perioperative management of pyeloplasty or ureteric surgery.

"Becoming Proximal" in Preclinical Medical Education: Community Engaged Learning Addressing Disparities in Care.

As the COVID-19 pandemic and national reckoning with racism reveal social disparities and their connection to health outcomes, we consider medical education's role in addressing pervasive health inequities and the labor of students, faculty, and community members who have come together to engage with these issues. We encourage institutions to consider a more socially-grounded model where all medical students-regardless of background, specialty, and career trajectory-participate in community-engaged and health equity-focused learning opportunities and curricula. As non-physician newcomers to medical education who are experienced in community-engaged work, in this commentary we consider how institutions might develop preclinical proximity-focused learning experiences. Reimagining academic medicine-community experiences has the potential to support medical students and community partnerships in fostering health equity in times of crisis and normalcy.

Hemşirelik Birinci Sınıf Öğrencilerinde Bilinçli Fakındalık Nefes Egzersizinin İlk Klinik Uygulama Stresine Etkisi

Aim: Clinical practices, which are an integral part of nursing education, create serious stress especially in first year nursing students. It is important to control the pre-clinical stress that nursing students experience. This study aimed to examine whether breath therapy is effective on the pre-clinical experience stress levels of first year nursing students. Methods: Semi-experimental in single group pre- post-test study design. 42 nursing first year students were included in the study. Before the application, Student Information Form, Visual Analog Scale and Pagana Clinical Stress Questionnaire were applied to all students. Then 30 minutes by expert researcher. breath therapy was applied and questionnaires were applied again. This process is performed once a week for a total of 3 times 30 minutes. repeated as. Results: The average age of the students was 19.13±.92. According to VAS, the stress level experienced by the students before the clinical practice was 6.77 ± 1.64, whereas it was determined as 2.64±2.06 after the third application. The mean clinical stress score before the application was 28.60±10.13 and after the third application it was 16.37±9.08. When the mean scores of the Clinical Stress Questionnaire of the students were compared separately according to the measurements, it was seen that their stress decreased in all measurements made before the application of breath therapy. Conclusion: With this study, conscious breathing therapy application was found to be effective in reducing the stress of nursing students who will go to the clinic for the first time.

Fractionated Dosing of CLR 131 in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

Background: CLR 131 is a novel targeted radiotherapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Based on initial preclinical and clinical experience and the radiosensitivity of MM, fractionated dosing of CLR 131 is being examined in RRMM in a Phase 1 trial (NCT02278315) and a Phase 2 trial, CLOVER-1 (NCT02952508). Methods: Both the Phase 1 and Phase 2 trials of CLR 131 aim to determine efficacy and safety in RRMM. Eligibility criteria include progressive or relapsed MM that is refractory to at least 1 proteasome inhibitor (PI) and 1 immunomodulatory (IMiD) drug with no upper limit to the number of prior lines of therapy. Prior autologous stem cell transplant (ASCT) and external beam radiation therapy are allowed (< 20% of total marrow irradiated). The Phase 1 trial was a single and fractionated ascending dose escalation safety study and the Phase 2 trial is evaluating 3 doses: a bolus dose and 2 fractionated doses. The fractionated doses of CLR 131 included infusion of either 31.25 mCi/m2 CLR 131 or 37.5 mCi/m2 CLR 131 (administered as 15.625 mCi/m2 or 18.75 mCi/m2, respectively, on day 1 and day 7 (± 1 day)) administered as a 30-minute intravenous infusion is reported here. Adverse events (AEs) are graded by NCI-CTCAE v4.03. Responses were determined using IMWG criteria as assessed by the investigator. Results: As of 30Jul2019, 10 subjects have received fractionated 31.25 mCi/m2 and 6 subjects fractionated 37.5 mCi/m2 CLR 131. In addition, 1 subject was scheduled to receive fractionated 37.5 mCi/m2 CLR 131 but died due to progressive disease prior to administration of the second dose; this subject is not included in the analyses below as they did not receive both fractionated doses. There is no upper age limit for enrollment and the median age for the 16 RRMM patients was 71 (range 51-83), including 6 females and 10 males with a median of 4 prior therapies (range 2 to 13). Seven patients had prior ASCT. CLR 131 demonstrated 100% disease control rate in subjects receiving either fractionated dose of CLR 131. The overall response rate (ORR) in the fractionated 37.5 mCi/m2 cohort is 50%. Three subjects in the cohort experienced a partial responses (PR), median time to response 43 days, and the other three had minimal responses (MR) with an average 39% reduction in m-protein. In this cohort, 80% of the subjects were either quad- or penta-refractory; all 80% were refractory to daratumumab. There were two subjects in the 31.25 mCi/m2 cohort with non-secretory disease and their status was followed by FDG-PET imaging. Both have been excluded from the evaluation of efficacy as their disease does not meet with IMWG criteria for response. No patients in this cohort achieved a PR or better however a majority of the subjects experienced a minimal response. The primary AEs include thrombocytopenia, anemia, neutropenia, and fatigue (Table 2). The hematologic AEs were expected, manageable and followed a predictable timeline to nadir (average. 40 days) and subsequent recovery (average 17 days post nadir). Conclusions: CLR 131 is a unique, first in class targeted radiotherapeutic for RRMM. Preliminary data for CLR 131 administered as a fractionated dose shows an acceptable and expected safety profile in this patient population. Fractionated dosing at 37.5 mCi/m2 has shown an efficacy signal and has been adopted as the standard for CLR 131 dosing in ongoing and future trials. Dose escalation to determine the highest tolerated dose is ongoing in the Phase 1 study and is currently examining a fractionated infusion of 40 mCi/m2 administered as 20 mCi/m2 CLR 131 on day 1 and day 7 (± 1 day). Based upon these data enrollment to the fractionated 37.5 mCi/m2 cohort of the Phase 2 trial continues. Disclosures Ailawadhi: Celgene: Consultancy; Amgen: Consultancy, Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy. Stiff:Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Unum: Research Funding. Ibrahim:Cellectar: Honoraria, Research Funding; Incyte: Research Funding; Pfeizer: Research Funding; Puma: Research Funding; Eli Lilly: Research Funding; Hoffman-LaRoche: Research Funding; Spectrum: Research Funding; Takeda: Research Funding. Cull:Celgene: Speakers Bureau; ADC Therapeutics: Research Funding. Green:GSK: Consultancy; Seattle Genetics: Research Funding; Juno Therapeutics: Consultancy, Patents & Royalties, Research Funding; Celgene: Consultancy; Cellectar: Research Funding. Oliver:Cellectar Biosciences: Employment. Longcor:Cellectar Biosciences: Employment, Equity Ownership.

Pharmacist perspectives and considerations for implementation of therapeutic oncology biosimilars in practice.

An overview of therapeutic oncology biosimilars, the U.S. biosimilars regulatory pathway, and the clinical development of selected biosimilar products is provided, including discussion of considerations in adopting biosimilars into oncology practice. Biosimilars are biologic agents that are highly similar to and have no clinically meaningful differences from an approved reference product in terms of safety, purity, and potency. There is a large market for cancer biologics, and approval of biosimilars has the potential to increase access to care and reduce costs. An abbreviated regulatory pathway for the development and approval of biosimilars defines a stepwise approach to demonstrating biosimilarity and conducting clinical comparative trials to confirm equivalent pharmacokinetics, efficacy, safety, and immunogenicity to the reference product. Three therapeutic biologics (bevacizumab, trastuzumab, and rituximab) have been used extensively in the treatment of a variety of cancers and are targets for biosimilar product development. Preclinical and clinical experience with 2 recently approved biosimilars to bevacizumab and trastuzumab is reviewed. Challenges faced by pharmacy and therapeutics committees when considering oncology biosimilars for formulary inclusion are discussed. Increased adoption of biosimilars could potentially lower treatment costs and improve access to biologics for patients with cancer. Key considerations in formulary review of biosimilars include the quality and quantity of data from comparative clinical trials, economic factors, manufacturer reliability, and challenges associated with incorporating biosimilars into practice.

Single Port Robotic Extra-peritoneal Dual Kidney Transplantation: Initial Preclinical Experience and Description of the Technique

ObjectiveTo describe the surgical technique for single-port robotic extraperitoneal dual kidney transplantation (DKT) using the SP surgical system (Intuitive Surgical, Sunnyvale, CA, USA) in a preclinical model. MethodsIn 1 male cadaver, the SP Surgical System was used to perform an extraperitoneal DKT. Kidney grafts were obtained from the local organ procurement organization, after being declined by all transplant centers. Kidneys were benched and wrapped in cold sponges. A periumbilical midline incision was performed. A kidney-shaped balloon was inserted through the incision to create the extraperitoneal space. SP robot was docked followed by dissection of iliac vessels bilaterally. The robot was undocked and the first graft was inserted through the wound retractor. The robot was re-docked and the renal vein anastomosis to external iliac vein was performed followed by renal artery anastomosis to external iliac artery using 5-0 monofilament sutures. Ureteroneocystostomy was performed using the Lich-Gregoir technique over a trasplant stent. Same steps were replicated for the left kidney transplant. Once procedures were done, kidneys were then harvested with the iliac vessels to examine the quality of the anastomosis. ResultsThe surgical procedure was completed successfully without the need of additional port or conversion to standard approach. Total bench kidney time was 30 minutes with overall transplantation time of 130 and 115 minutes of the right and left kidney, respectively. ConclusionWe demonstrated the feasibility of single-port extraperitoneal DKT using the novel SP robotic platform. Limitations include the preclinical model. Further assessment is necessary in a truly clinical setting.

Self-reported confidence and anxiety over endodontic procedures in undergraduate students-Quantitative and qualitative study.

The current literature shows a growing interest to assess the feelings and perceptions of students associated with the performance of elective endodontic procedures. This study aimed to evaluate the students' anxiety and self-perceptions related to performing such treatments. Forty-five students participated in the research (G1=22 beginners students; G2=23 senior students). Demographic data, STAI-State and Numerical Rating Scale (NRS) for pre-operative anxiety were completed before the appointment with patient. The STAI-Trait; NRS for post-operative anxiety; previous experiences in endodontics; and level of confidence in each stage of endodontic treatments were collected after appointment. Focal groups for qualitative data collection were performed on separate occasion. Both groups showed higher scores in STAI-State than for STAI-Trait scale. G1 showed higher levels of anxiety in the pre-operative, compared with post-operative moment in the NRS scale. G2 reported feeling more confidence to insert intracanal medication and to restore teeth between appointments than G1. In both focus groups, participants reported insecurity in performing endodontic procedures due to difficulty in visualisation and to anatomic complexities. G1 reported that all the confidence they had was based in pre-clinical experience, and G2 mentioned concern about the end of graduation. The participants' anxiety diminishes as they gain more experience in performing endodontic procedures. However, as they approach the end of the course anxiety levels increase. Greater availability of elective courses in endodontics could be a valuable alternative to provide students with more exposure to and experience with these procedures.

Splenic artery denervation: target micro-anatomy, feasibility, and early preclinical experience

This study sought to evaluate perisplenic artery nerve distribution and the feasibility of splenic artery denervation (SDN). The NEXION radiofrequency catheter was used to perform SDN in healthy and inflammatory arthritis pigs. Splenic artery anatomy, nerve distribution, and splenic norepinephrine (NEPI) levels were evaluated before and after SDN. Perisplenic artery nerves were primarily distributed within 2.5 mm of the arterial lumen and were largely sympathetic on the basis of tyrosine hydroxylase expression. The pancreas, tended to be circumferentially positioned around the proximal splenic artery, typically >2.5 mm from the lumen, ensuring that most of the nerves could be targeted without affecting this sensitive organ. The mid segment of the splenic artery was relatively free of contact with the adjacent pancreas. Splenic NEPI levels and nerve abundance followed a decreasing gradient from the proximal to distal splenic artery. SDN resulted in significant reductions in splenic NEPI levels at day 14 (60.7%, P = 0.024) in naïve pigs and day 45 (100%, P = 0.001) in inflammatory arthritis pigs. There was no significant effect of SDN on joint soft tissue injury or circulating inflammatory markers in the inflammatory arthritis model. The majority of perisplenic arterial nerves are within close proximity of the lumen and are primarily sympathetic efferent fibers. Nerves in the mid-segment may be the preferred SDN target given their proximity to the artery and paucity of periarterial off-target organs. SDN appears safe and effective at reducing splenic NEPI levels.

Assessing likelihood of using the Bruininks-Oseretsky test of motor proficiency to predict preclinical performance of dental students.

ObjectiveThe acquisition of motor skills is a key competency for the practice of dentistry, and innate abilities have been shown to influence motor performance. Thus, finding the most efficient manual dexterity tests may predict performance of dental students. The current study used the Bruininks–Oseretsky Test of Motor Proficiency, to assess motor skills of first year (D1) and second year (D2) dental students.Materials and methodsThree fine motor subsets of the BOT‐2—fine motor precision, fine motor integration, and manual dexterity—were administered to D1 and D2 dental students in 2017 and 2018. The BOT‐2 subset scores of D1 students were compared with those of D2 students, who had preclinical dental experiences. For D2 students, we tested for correlations between BOT‐2 subset scores and performance scores in a preclinical operative dentistry course.ResultsNo differences were found between D1 and D2 students for any BOT‐2 subtest scores (all Ps > .09). No correlations were found between total scores of each BOT‐2 subtest and the operative dentistry course for D2 students (all Ps > .20).ConclusionsOur results suggested the BOT‐2 was not predictive of manual skills of dental applicants or preclinical dental students. Although we assumed students would perform well with instruction, practice, and feedback, we were unable to determine whether innate abilities influenced acquisition of manual dexterity skills. More research about the acquisition of technical clinical skills in dentistry is required.

Irreversible electroporation for catheter-based cardiac ablation: a systematic review of the preclinical experience.

Irreversible electroporation (IRE) utilizing high voltage pulses is an emerging strategy for catheter-based cardiac ablation with considerable growth in the preclinical arena. A systematic search for articles was performed from three sources (PubMed, EMBASE, and Google Scholar). The primary outcome was the efficacy of tissue ablation with characteristics of lesion formation evaluated by histologic analysis. The secondary outcome was focused on safety and damage to collateral structures. Sixteen studies met inclusion criteria. IRE was most commonly applied to the ventricular myocardium (n = 7/16, 44%) by a LifePak 9 Defibrillator (n = 9/16, 56%), NanoKnife Generator (n = 2/16, 13%), or other custom generators (n = 5/16, 31%). There was significant heterogeneity regarding electroporation protocols. On histological analysis, IRE was successful in creating ablation lesions with variable transmurality depending on the electric pulse parameters and catheter used. Preclinical studies suggest that cardiac tissue ablation using IRE shows promise in delivering efficacious, safe lesions.

Rationale for Biologic Augmentation of Rotator Cuff Repairs.

The structural integrity of rotator cuff repair (RCR) has been a primary focus for shoulder surgeons seeking long-term clinical and functional success. Improvements in surgical techniques have allowed for superior initial biomechanical fixation. However, tendon healing remains a significant clinical problem even after rigid time-zero repair. The lack of long-term healing has led to increased interest in biologic augmentation to improve tendon-to-bone healing. This interest has led to a rise in the investigation of small molecular therapies, cell-based strategies, and tissue-derived treatments offering surgeons a new therapeutic toolbox for potentially improving RCR long-term outcomes. However, the delivery, efficacy, and safety of these treatments remain under investigation. Additional well-designed, high-level studies are of paramount importance in creating evidence-based guidelines for the implementation of new biologic solutions. This review article discusses the current preclinical, translational, and clinical experience with and rationale for biologic augmentation in RCR.

Early Preclinical Experience with a Novel Endobronchial Radiofrequency Ablation System for Lung Cancer Treatment.

This paper introduces a novel technology for treating early-stage non-small cell lung cancer using an endobronchial approach via a flexible radiofrequency ablation (RFA) catheter. Methods - The RFA system consisted of an ablation catheter, radiofrequency generator, irrigation pump for infusion of hypertonic saline (HS) and a laptop. The catheter carried an occlusion balloon, a 5 mm long RF electrode, with irrigation holes, and a 1 mm long electrode for bipolar impedance measurements. The outer diameter was 1.4 mm for compatibility with current bronchoscopes, navigation systems and radial EBUS. The RFA system was extensively bench tested on fresh heart, liver and lung animal tissues using power levels of 30 - 60 W, RF energy delivery durations of 3 - 15 min and HS concentrations of 5% and 23.4%. Two swine were then treated at 60 W for 15 min per bronchus. Several bronchi were involved. For both animals and for all treatment sites, 20% HS was used. Animals were survived for six weeks. Results - Bench studies showed that 60 W, 7 - 15 min ablations can produce large ablation volumes, in excess of 3 - 4 cm diameter. In the chronic animal study, no clinically adverse events occurred. There was no evidence of hemorrhage. Animals vital signs, breathing patterns and their behavior were normal throughout the six-week period. Their appetite was normal and they gained weight according to expectations. The RF ablation created discrete volumes of thermal coagulative necrosis which were subsequently encapsulated ("walled off") by zones of organized fibrosis. The dimensions of coagulative necrotic sequestra met expectations, as at six weeks they exceeded volumes corresponding to 2 cm nodules, the size of tumors normally addressed in the peripheral lung by localized therapy. Conclusion - This therapy showed promise. Appropriate energy settings combined with suitable treatment locations safely produced large ablation volumes of uniform thermal coagulative necrosis. Further studies and optimization of treatment parameters can develop it into a mainstream therapy for treating early-stage lung tumors in humans.