High-Frequency Irreversible Electroporation Using 5,000-V Waveforms to Create Reproducible 2- and 4-cm Ablation Zones-A Laboratory Investigation Using Mechanically Perfused Liver.

PURPOSE: To investigate if high-frequency irreversible electroporation (H-FIRE) treatments can be delivered at higher voltages and with greater energy delivery rates than currently implemented in clinical irreversible electroporation protocols. MATERIALS AND METHODS: Treatments using 3,000 V and 5,000 V were administered to mechanically perfused ex vivo porcine liver via a single applicator and grounding pad (A+GP) as well as a 4-applicator array (4AA). Integrated energized times (IET) 0.01-0.08 seconds and energy delivery rates 25-300 µs/s were investigated. Organs were preserved at 4°C for 10-15 hours before sectioning and gross analysis using a metabolic stain to identify the size and shape of ablation zones. RESULTS: A+GP ablations measured between 1.6 cm and 2.2 cm, which did not increase when IET was increased from 0.02 seconds to 0.08 seconds (P > .055; range, 1.9-2.1 cm). Changes in tissue color and texture consistent with thermal damage were observed for treatments with energy delivery rates 50-300 µs/s, but not for treatments delivered at 25 µs/s. Use of the 4AA with a 3-cm applicator spacing resulted in ablations measuring 4.4-4.9 cm with energy delivery times of 7-80 minutes. CONCLUSIONS: H-FIRE treatments can rapidly and reproducibly create 2-cm ablations using an A+GP configuration. Treatments without thermal injury were produced at the expense of extended treatment times. More rapid treatments resulted in ablations with varying degrees of thermal injury within the H-FIRE ablation zone. Production of 4-cm ablations is possible using a 4AA.

Prognostic value of colonic and peripheral venous lactate measurements in horses with large colon volvulus.

OBJECTIVE: To determine the prognostic value of (1) colonic venous lactate or peripheral lactate values obtained before and after manual correction of a large colon volvulus and (2) a combination of variables including pelvic flexure biopsy. STUDY DESIGN: Prospective clinical study. ANIMALS: Forty adult horses in which large colon volvulus was diagnosed intraoperatively. METHODS: Colonic venous, peripheral venous, and arterial blood samples were collected to measure lactate values before and after manual correction. Mucosal biopsy samples were obtained in cases that underwent enterotomy or colonic resection and anastomosis. Interstitium to crypt (I:C) ratio and hemorrhage scores were measured. Optimal cutoff values were determined by receiver operator curve analysis, and associations between variables and short-term outcome were determined by univariable regression. Short-term survival was defined as horses being discharged from the hospital. P ≤ .05 was considered significant. RESULTS: No association was found between colonic venous lactate values before (P = .011) or after (P = .201) manual correction of large colon volvulus and determination of short-term outcome. Peripheral venous lactate at admission ≥3.2 mmol/L and after manual correction ≥5 mmol/L, arterial lactate postmanual correction ≥3.53 mmol/L, and histomorphometric measurements of mucosal hemorrhage ≥3 and I:C ratio > 1 were associated with poor short-term outcome. CONCLUSION: Peripheral lactate values, histomorphometric measures of I:C ratio, and hemorrhage score provided prognostic information that could help guide recommendations made to owners. CLINICAL SIGNIFICANCE: Peripheral lactate values after manual correction provide important intraoperative diagnostic information to assist in predicting case outcome in the operative and immediately postoperative period.

Duty hours restriction for our surgical trainees: An ethical obligation or a bad idea?

To ensure patient safety and protect the well-being of interns and residents, the Accreditation Council for Graduate Medical Education (ACGME) issued guidelines in 2003 limiting the working hours of physician trainees. Although many supported the goals of the ACGME, institutions struggled to restructure their programs and hire staff required by this unfunded mandate. Numerous studies have analyzed the effects of duty hours restrictions on patient outcomes and physician training over the past 15 years. Most agree that duty hours restrictions improved well-being of house officers, but these improvements came at the expense of continuity, and patient hand-offs led to medical errors. Effects on resident training are program specific, with duty hours restrictions having the most deleterious effects on surgical disciplines. Because veterinary specialists assume a similar role in providing 24-hour patient care, interns and residents face work-related stress as a result of extended working hours, on-call duty, and an increasingly complex caseload. The North Carolina State Veterinary Hospital is staffed by approximately 100 house officers representing almost every veterinary specialty group. We surveyed departing house officers regarding their quality of life and training experience. Sixty-six percent of interns and residents reported that they do not have time to take care of personal needs, and 57%-62% felt neutral or dissatisfied with their mental and physical well-being. Most trainees believed that decreased duty hours would improve learning, but 42% believed that decreased caseload would be detrimental to training. Veterinary educators must consider post-DVM veterinary training guidelines that maintain patient care with a good learning environment for interns and residents.

Effects of hyaluronate-carboxymethylcellulose membranes on the clinical outcome of horses undergoing emergency exploratory celiotomy.

OBJECTIVE: To determine the influence of hyaluronate-carboxymethylcellulose (HA-CMC) membranes applied to intestinal anastomoses or enterotomies on postoperative complications after emergency exploratory celiotomy. STUDY DESIGN: Multicenter retrospective case-controlled series. ANIMALS: Adult horses (59 in the HA-CMC group and 91 controls). METHODS: Medical records from 4 referral hospitals were searched for horses ≥1 year of age, treated between 2008 and 2014 with emergency exploratory celiotomy, and surviving at least 24 hours postoperatively. Horses receiving repeat celiotomy during the same hospitalization were excluded. Horses who received HA-CMC were matched with controls who did not receive HA-CMC but had similar intestinal lesions and procedures at the same referral hospital. Postoperative complications (colic, nasogastric reflux, fever, incisional infection, and septic peritonitis), duration of hospitalization, and survival were compared between groups. Data were compared between horses by t test, Wilcoxon signed rank test, and χ2 test. RESULTS: The volume of nasogastric reflux at admission (P = .02) and the duration of administration of lidocaine after surgery (P = .02) were greater in horses with HA-CMC membranes than in controls. No difference in postoperative complications or survival was detected between groups: 48 of 59 (81%) horses treated with HA-CMC survived until discharge from the hospital compared with 80 of 91 (88%) horses in the control group (P = .27). Fifteen of 21 horses treated with HA-CMC and 30 of 43 horses in the control group survived >12 months after hospital discharge. CONCLUSION: Application of HA-CMC membranes to anastomoses or intestinal incisions did not influence postoperative complications or survival after emergency celiotomy compared with controls. CLINICAL SIGNIFICANCE: The safety and efficacy of HA-CMC membrane application to intestinal sites during colic surgery in horses is equivocal.

Opinions regarding equine veterinarian attire and attributes: results of a horse owner survey.

OBJECTIVE: To investigate potential equine clients' perceptions of equine veterinarians based on attire. SAMPLE: 763 horse owners/lessees. METHODS: Participants were invited to complete a survey shared mainly via equestrian social media pages between August and October 2022.1-3 Survey participants were shown pictures of a male veterinarian and a female veterinarian in 7 outfits ranging from casual to business attire and were asked to score the veterinarian on 7 traits: easygoing attitude, friendliness, compassion, trustworthiness, professionalism, competence, and cost of services. The survey asked which of the traits were most valued in an equine veterinarian, as well as whether various aspects of appearance including tattoos, piercings, and hair dyed a nonorganic color were acceptable for equine veterinarians. RESULTS: Of the 2,655 individuals who opened the survey, 763 responses were included. Respondents were predominantly female (743/763 [97.4%]) from rural areas (493/763 [64.6%]). Only 37.1% (283/763) of respondents agreed that what a veterinarian wears influences their confidence in them. The highest-ranked traits in an equine veterinarian were knowledge/competency (mean ± SD, 1.46 ± 0.98), followed by trustworthiness (2.34 ± 1.08) and compassion (3.50 ± 1.20), with coveralls and scrubs being the preferred attire clients associated with these attributes (with the exception of compassion, for which polo shirt/jeans was the preferred attire). T-shirt/jeans was consistently ranked lowest by respondents in association with these attributes, except in the area of compassion, where polo shirt/black pants was ranked lowest. CLINICAL RELEVANCE: Our findings suggested the attire and appearance of equine veterinarians can impact client perceptions, with veterinarians wearing scrubs and coveralls associated with higher competency and trustworthiness.

Laparoscopic-assisted colpotomy for ovariectomy in the mare.

OBJECTIVE: To describe a technique for ovariectomy through a colpotomy using a chain écraseur with laparoscopic guidance and report outcome in 4 mares. STUDY DESIGN: Case series. METHOD: After insertion of a laparoscope into the abdomen through the left flank, colpotomy was performed to allow introduction of an écraseur into the caudal aspect of the abdomen. Grasping and removal of the ovary and evaluation of the pedicle was observed via the laparoscope. The laparoscope was then inserted in the right flank for right ovariectomy. The colpotomy was closed in a continuous suture pattern using laparoscopic or long needle holders. RESULTS: Insertion of a laparoscope allowed ready identification of the ovaries and capture within an écraseur, including assurance that no other tissues were contained within écraseur chain. The mesovarial pedicles were easily be examined for hemorrhage. Surgical time for ovariectomy was 10-15 minutes with no postsurgical complications. Closure of the colpotomy healed without complications. CONCLUSION: Laparoscopic-assisted écraseur ovariectomy is inexpensive, rapid, and a safe alternative to other methods of open and laparoscopic ovariectomy.

Development and Formative Evaluation of a Low-Fidelity Equine Castration Model for Veterinary Education.

Entrustable Professional Activities (EPAs) are units of activity that early-stage professionals perform in the workplace that necessitate simultaneous integration of multiple competencies. EPA #6 requires students to perform a common surgical procedure on a stable patient, including pre-operative and post-operative management. Castration is one of the most common surgeries performed by equine primary care practitioners and is considered an "entry-level competency" for veterinary graduates entering equine private practice, however, to our knowledge there are no equine castration models available for veterinary student education. Therefore, we developed an inexpensive, low-fidelity model of equine field castration and evaluated it using a mixed-methods approach. Two different groups of students, with or without model experience, completed surveys before and after live horse castration. Students who used the model also completed model specific surveys. Videos of the students completing the model were evaluated by at least two different equine veterinary faculty using a 15-point rubric, and inter-rater reliability of the rubric was determined. After completing the model, students reflected on strengths and weaknesses of their performance. From our student survey results, we determined that student attitudes toward the model were mostly positive. Interestingly, there were several student attitudes toward the model that became significantly more favorable after live horse castration. Prior to live horse castration, there was no significant difference in confidence in model vs. no-model groups. Following live horse castration, students who used the model had higher confidence in procedure preparation and hand-ties than students who did not use the model, but they had lower scores for confidence during patient recovery. When reflecting on model castration, students most commonly cited preparation and surgical description as strengths, and ligature placement and hand-ties as weaknesses. Experts provided several suggestions to improve the model, including incorporation of emasculators and the need for better model stabilization. Our findings suggest that both students and veterinary educators feel that this low-fidelity model has educational value. Rubric performance metrics were favorable, but additional steps are needed to improve grading consistency among educators. Future research will determine whether student performance on the model is predictive of competence score during live-horse castration.

Comparison of histomorphometric characteristics of dorsal colon and pelvic flexure biopsy specimens obtained from horses with large colon volvulus that underwent resection.

OBJECTIVE: To determine the degree of histomorphometric damage in dorsal colon and pelvic flexure biopsy specimens (DCBSs and PFBSs, respectively) obtained from horses with large colon volvulus (LCV) and assess the accuracy of predicting short-term outcome for those horses on the basis of DCBS or PFBS characteristics. ANIMALS: 18 horses with ≥ 360° LCV that underwent large colon resection. PROCEDURES: During surgery, biopsy specimens from the dorsal colon resection site and the pelvic flexure (when available) were collected from each horse. Interstitial-to-crypt (I:C) ratio (ratio of the lamina propria space occupied by the interstitium to that occupied by crypts), hemorrhage within the lamina propria (mucosal hemorrhage score [MHS] from 0 to 4), and percentage losses of glandular and luminal epithelium were determined in paired biopsy specimens and compared to determine optimal cutoff values for calculating the accuracy of DCBS and PFBS characteristics to predict short-term outcome (survival or nonsurvival after recovery from surgery). RESULTS: Paired biopsy specimens were obtained from 17 of the 18 horses. The I:C ratio and percentage glandular epithelial loss differed between DCBSs and PFBSs. For DCBSs, an I:C ratio ≥ 0.9 and MHS ≥ 3 each predicted patient nonsurvival with 77.8% accuracy. For PFBSs, an I:C ratio ≥ I and MHS ≥ 3 predicted patient nonsurvival with 70.6% and 82.4% accuracy, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Although different, histomorphometric measurements for either DCBSs or PFBSs could be used to accurately predict short-term outcome for horses with LCV that underwent large colon resection, and arguably PFBSs are easier to collect.

Electro-thermal therapy: Microsecond duration pulsed electric field tissue ablation with dynamic temperature control algorithms.

Electro-thermal therapy (ETT) is a new cancer treatment modality which combines the use of high voltage pulsed electric fields, dynamic energy delivery rates, and closed loop thermal control algorithms to rapidly and reproducibly create focal ablations. This study examines the ablative potential and profile of pulsed electric field treatments delivered in conjunction with precise temperature control algorithms. An ex vivo perfused liver model was utilized to demonstrate the capability of 5000 V 2 µs duration bipolar electrical pulses and dynamic temperature control algorithms to produce ablations. Using a three applicator array, 4 cm ablation zones were created in under 27 min. In this configuration, the algorithms were able to rapidly achieve and maintain temperatures of 80 °C at the tissue-electrode interface. A simplified single applicator and grounding pad approach was used to correlate the measured ablation zones to electric field isocontours in order to determine lethal electric field thresholds of 708 V/cm and 867 V/cm for 45 °C and 60 °C treatments, respectively. These results establish ETT as a viable method for hepatic tumor treatment with ablation profiles equivalent to other energy based techniques. The single applicator and multi-applicator approaches demonstrated may enable the treatment of complex tumor geometries. The flexibility of ETT temperature control yields a malleable intervention which gives clinicians robust control over the ablation modality, treatment time, and safety profile.

Temperature Dependence of High Frequency Irreversible Electroporation Evaluated in a 3D Tumor Model.

Electroporation is a bioelectric phenomenon used to deliver target molecules into cells in vitro and irreversible electroporation (IRE) is an emerging cancer therapy used to treat inoperable tumors in situ. These phenomena are generally considered to be non-thermal in nature. In this study, a 3D tumor model was used to investigate the correlation between temperature and the effectiveness of standard clinical IRE and high frequency (H-FIRE) protocols. It was found for human glioblastoma cells that in the range of 2 to 37 °C the H-FIRE lethal electric field threshold value, which describes the minimum electric field to cause cell death, is highly dependent on temperature. Increasing the initial temperature from 2 to 37 °C resulted in a significant decrease in lethal electric field threshold from 1168 to 507 V/cm and a 139% increase in ablation size for H-FIRE burst treatments. Standard clinical protocol IRE treatments resulted in a decrease in lethal threshold from 485 to 453 V/cm and a 7% increase in ablation size over the same temperature range. Similar results were found for pancreatic cancer cells which indicate that tissue temperature may be a significant factor affecting H-FIRE ablation size and treatment planning in vivo while lower temperatures may be useful in maintaining cell viability for transfection applications.

Multicenter Placebo-Controlled Randomized Study of Ethyl Pyruvate in Horses Following Surgical Treatment for ≥ 360° Large Colon Volvulus.

Identifying therapies that mitigate ischemic colonic injury and improve mucosal healing and intestinal viability are crucial to improving survival in horses with ≥360° large colon volvulus (LCV). Ethyl pyruvate is the ethyl ester of pyruvate with diverse pharmacologic effects that limit ischemic injury and hasten intestinal mucosal repair in preclinical rodents, sheep and swine models. The objective of this study was to determine the effects of ethyl pyruvate on systemic indices of colon viability, expression of inflammatory genes in whole blood, morbidity and survival after surgical correction of LCV compared to controls. Horses received either 150 mg/kg ethyl pyruvate in 1 liter lactated Ringer's solution (LRS) or 1 liter LRS intravenously (IV) every 6 h for 24 h following surgical recovery for correction of LCV. Colic duration, perioperative heart rate (HR), packed cell volume (PCV), total solids (TS), blood L-lactate concentration, surgical time, intraoperative episodes of hypoxemia and hypotension, expression of inflammatory cytokine genes, fecal consistency and survival to hospital discharge were compared between ethyl pyruvate treated horses and controls. Twenty-two horses, 12 receiving ethyl pyruvate and 10 controls, were enrolled in the study. Ethyl pyruvate was safely administered to horses following surgical correction of LCV. No significant effects of ethyl pyruvate on post-operative variables, including survival, were found. Seven of 12 ethyl pyruvate treated horses and 5/10 controls survived to hospital discharge. Higher HR, PCV and blood L-lactate concentration at the time of hospital admission, P = 0.005, 0.01, 0.04, respectively, 24 h after surgery, P = 0.001, 0.03, 0.02, respectively, were associated with death. Heart rate, P = 0.005, 48 h after surgery was associated with death. Ethyl pyruvate was safely administered to horses following correction of LCV with no apparent adverse events but was not associated with improved post-operative outcomes including survival. A larger, randomized control trial is needed to fully evaluate the effectiveness of ethyl pyruvate. A major limitation of this investigation is the small sample size, making the study underpowered and creating a high possibility of type II error.

Analysis of sodium carboxymethylcellulose administration and related factors associated with postoperative colic and survival in horses with small intestinal disease.

OBJECTIVE: To analyze the effect of the intraoperative use of sodium carboxymethylcellulose (CBMC) and related perioperative factors on postoperative colic and survival in horses that had abdominal surgery for colic. STUDY DESIGN: Retrospective study. ANIMALS: Horses (n=203) that had surgery for small intestinal disease; 33 horses had intraoperative administration of CBMC. METHODS: Information was obtained from medical records for 170 horses that had surgery for colic before use of CBMC and 33 horses that had intraoperative CBMC. Kaplan-Meier survival curves were used to estimate median survival time and a Cox proportional hazards model was used to estimate the hazard ratio for the effect of CBMC and other perioperative variables on survival. RESULTS: Seventy-five percent of horses administered CBMC survived to 180 days, whereas 75% of untreated horses survived 8 days (median survival time=18 days). Horses not administered CBMC were twice as likely to die compared with horses administered CBMC. Horses that had postoperative ileus (POI) were 1.4 times more likely to die than horses without ileus. Similarly, horses with signs of colic after surgery were 1.3 times more likely to die than horses without postoperative signs of colic. CONCLUSIONS: CBMC administration is seemingly protective against death and prolongs survival when used intraoperatively in horses with small intestine disease, particularly horses with postoperative colic or POI. Both POI and colic increased risk of death after surgery. CLINICAL RELEVANCE: Intraoperative administration of CBMC in horses that have surgery for small intestinal disease may improve survival, possibly by reducing early adhesion formation.