Hernia

We wish to use the images a mother would have done as part of her normal medical care and make both 3D animations and 3D models of the baby and it's CDH. This will both help the parents see what the problem is and also allow the surgeons, who will operate on the baby once it has been born, to see the size of the hole and what organs are in the wrong place.

The study rationale is that prior to conducting a multisite randomized trial, it is necessary to identify relevant outcomes, understand barriers to greater use of local anesthesia, test study procedures, and confirm our ability to adequately recruit and randomly assign participants. Additionally, the proposed study will provide the applicant with critical training in the design, conduct, and analysis of clinical trials. This will uniquely position the applicant to change surgical care for older adults. More specifically, the investigators plan to demonstrate the ability to successfully randomize Veterans aged 60 years and older to local versus general anesthesia for inguinal hernia surgery, and to validate processes and instruments to measure relevant outcomes. Although the original NIA-approved proposal involved only two arms, open hernia repair using local anesthesia and open repair using local anesthesia, the study team subsequently published a paper that showed using local anesthesia for open hernia repair may also be superior to laparoscopic or robotic hernia repair. Consequently, a third arm is added to our pilot study: laparoscopic or robotic hernia repair with general anesthesia (these surgical approaches cannot be done using local anesthesia). The rationale is that use of laparoscopic or robotic inguinal hernia surgery, while still less common than open repair, is becoming more common and no prior randomized trials have compared laparoscopic/robotic surgery versus open repair using local anesthesia. Local or general anesthesia are the primary methods of anesthesia for inguinal hernia surgery for most surgeons (though some perform the operation under spinal or regional anesthesia, this is rare). Both approaches are used in clinical practice with acceptable known risks and complications. General anesthesia is associated with risks of hypotension, venous thromboembolism, heart attack, stroke, pulmonary dysfunction, cognitive dysfunction, allergic reaction, urinary retention, and malignant hyperthermia. The main risks of local anesthesia include allergic reaction and hypotension (when the anesthetic is improperly injected into a blood vessel). The primary objective is to: 1. demonstrate ability to successfully recruit, randomize, and retain patients aged 60 years and older for a randomized trial of local versus general anesthesia for inguinal hernia surgery, and 2. establish the ability to measure relevant outcomes and test protocols and study instruments for measuring key outcomes. The secondary objective is to generate preliminary comparisons between the study arms, to inform effect size estimates for a larger multisite trial.

The goal of this observational study is to understand the utility of force feedback instruments in surgeries that are done using the da Vinci 5 robot.

Congenital diaphragmatic hernia (CDH) occurs in approximately 1 in 3000 US live births, similar to the incidence seen within the Utah Birth Defects cohort. An early developmental diaphragmatic defect leads to herniation of abdominal contents into the thoracic cavity. Such visceral herniation compromises lung growth and alters pulmonary vascular development. This is reflected postnatally as respiratory failure, pulmonary hypertension (PH) and overall cardiopulmonary dysfunction, particularly post-repair. Survival among all liveborn infants is approximately 70% and has not changed in the past 20 years. A major contributor to morbidity and mortality of this neonatal cohort is persistent PH. CDH-related PH is related to 1) arteriolar remodeling with increased vascular smooth muscularization leading to smaller diameters of the distal arterioles; 2) a hypodense vascular bed related to compromised lung growth; and 3) endothelial dysfunction resulting in increased vasoreactivity. Given this multifactorial nature of CDH-related PH, post-natal treatment is often challenging. Moreover, there is an increased risk of PH crises with post-operative inflammatory cascades and fluid shifts. Currently, optimal management of post-repair PH remains poorly investigated. An important pulmonary vasodilatory cascade includes the nitric oxide pathway, which acts via increases in cyclic guanosine monophosphate (cGMP). Sildenafil citrate is a highly selective phosphodiesterase-5 inhibitor that increases cGMP levels, leading to smooth muscle relaxation and an anti-proliferative effect within the pulmonary vasculature. It is used off-label for many neonatal PH disorders, including PH associated with bronchopulmonary dysplasia and idiopathic persistent PH. A multi-center trial evaluating the use of sildenafil in premature infants with bronchopulmonary dysplasia (NCT04447989) is currently underway. Pharmacokinetics of sildenafil in infants have previously been studied with a dosing range of 1mg/kg every 6-8 hours. In addition, sildenafil administration in the neonatal cohort appears safe and well-tolerated. Off-label use of sildenafil to treat CDH-related PH is increasing, despite limited evidence of efficacy in neonates with CDH. Use is based on the hypothesis that administering sildenafil post-hernia repair at a time when physiological changes are rapidly shifting may assist with pulmonary vascular relaxation to alleviate PH. Improvement in PH may ultimately benefit post-operative cardiorespiratory stability. Left ventricular eccentricity index (LVEI) is a non-invasive echocardiographic measure of such PH. LVEI is an objective measure that reflects the more subjective measure of left ventricular septal flattening. Its use decreases inter-observer variability and is a reliable assessment of neonatal PH. Elevated values of LVEI ≥ 1.4 are associated with right ventricular suprasystemic pressures. Normative values of LVEI in neonates without PH are ≤1. Most neonates with CDH born within the Mountain West referral basin are managed at a quaternary care center, Primary Children's Hospital (PCH). PCH neonatal intensive care unit (NICU) averages 19 infants of CDH per year (range 12-24). Preliminary data shows that between 2007 and 2020, 60-85% of neonates with CDH managed at PCH manifest post-operative PH with LVEI values averaging between 1.4 to 2 on the post-repair echocardiogram. Of these neonates with PH, approximately 25% have been treated with off-label sildenafil. However, neither the PCH clinical care group nor others have developed/published a standardized approach for either initiating or discontinuing sildenafil therapy in this group of patients. Equipoise exists within the PCH clinical care group as the effectiveness of sildenafil use in neonates with CDH has not been well studied. Thus, the aim of this study is to assess the safety and effectiveness of sildenafil therapy for PH in neonates with CDH within the Utah cohort. Given the relatively short-term outcome and small sample size for this trial, this data can be used to support a larger multicenter randomized trial targeting long-term cardiopulmonary outcomes of infants with CDH and post-repair PH.

Within this protocol we propose to perform abdominal wall transplantation in 5 subjects, either as an isolated abdominal wall or in combination with another organ transplant. Each subject will be followed for a study period of 18 months. Participants receiving an isolated abdominal wall or abdominal wall in combination with another organ transplant will receive the standard immunosuppression therapy as the non-vascularized composite allograft organ transplant. These patients will be studied to determine efficacy of the abdominal wall transplant to restore function of the defective abdominal wall for a study period of 18 months at Duke University Medical Center.

This study will evaluate lifting restrictions in the postoperative period after inguinal hernia repair. Patients will be consented to the study via in person and electronic methods. Patients will be asked to answer a questionnaire regarding their current pre-operative activity levels in order to establish a baseline. Patients will undergo surgery according to normal medical recommendations and patient preference. Patients will be randomized into one of two groups: a control group told to practice standard of care at Eastern Colorado VA with return to activity precautions (6 weeks for open surgery, 2 weeks for minimally invasive surgery) and a treatment group told to "return to activity as tolerated/comfortable and stop activity if pain present". Patients will be observed in post-operative clinics and asked clinical questions, as well as questionnaires to assess their surgical experience, when they returned to activity, and overall quality of life. Medical charts will be reviewed in order to compare differences in responses and behaviors between the two groups and these data points will be recorded in a password protected document for data analysis. This study aims to identify if lengthy recommendations for convalescence after inguinal hernia surgery are necessary and determine the impact of allowing the individual patient to have some autonomy in a recommendation to return to physical activity based on their own comfort level. This study could provide the surgical community with a more structured response after this common surgical procedure, as well as potentially reduce convalescence times for individual patients, leading to less economic burden on the individual and the community with returning to work precautions.

A prospective, post-market, multicenter, nonrandomized, single-arm, interventional clinical study of the MaxTack™ Motorized Fixation Device when used for fixation of prosthetic material to soft tissue in minimally invasive ventral hernia repair procedures. Subjects will be followed in the short term (1 and 3 months) and long term (12 months) to evaluate safety and performance of the device. The study is being conducted in two phases. Phase 1 will enroll approximately 33 subjects at up to 3 sites in the United States. Based on regulatory needs, Phase 2 may enroll additional subjects at approximately 10 US sites, for a total of up to 110 subjects across both phases.

The study is a prospective observational, physiological study running across the two trust that form the Liverpool Neonatal Partnership; Liverpool Women's Hospital NHS Foundation Trust and Alder Hey Children's Hospital Foundation Trust. There is no study intervention and therefore all participants will be managed in accordance with existing local protocols and current accepted clinical practice. Participants will receive standard neonatal and surgical care as per the local clinical guidelines. The participant will have routine blood tests taken as part of their routine care. No additional blood or blood tests will be taken for the SuNDiAL study. The study will involve the analysis of any blood left over from samples taken routinely pre and postoperatively in infants who have undergone abdominal surgery. Residual serum samples will be analysed from the blood samples taken for routine blood monitoring in the infants enrolled in the study. Biochemical samples will undergo Enzyme-linked immunosorbent assay (ELISA) analysis for ADMA and arginine. The study period is from preoperatively until 30 days post operatively or until the baby fully recovers from surgery, marked by being fully fed with milk into their stomach. The aim is to obtain at least 1 measurement preoperatively, and a minimum of 4 measurements in the post-operative period. The expectation is that 3-5 measurements first 10 postoperative days should be achievable. The SuNDiAL study will aim to determine if the level of ADMA and/or Arginine and/or the Arginine to ADMA ratio is associated with the time taken to recover following major abdominal surgery in neonates born after 35 weeks gestation. Recovery will be measured as the time taken to no longer require intravenous nutrition following surgery as the primary objective. The secondary objectives include: 1. To develop a mathematical model of postoperative ADMA and/or ARG/ADMA ratio. This will allow future randomised controlled trial designs investigating postoperative recovery time to include ADMA and ARG/ADMA in the study protocol. This modelling has the potential to develop future arginine supplementation protocols to target and/or refine arginine dosage and duration based on the trajectory of the ADMA levels or arginine:ADMA ratio. This approach includes specific post operative complications following surgery that may delay recovery (such as mortality, wound healing, sepsis, parenteral nutrition cholestasis) 2. To compare ADMA and/or ARG/ADMA ratio in specific gastrointestinal conditions that require major abdominal surgery. 3. To assess ADMA and the ARG/ADMA ratio in specific gastrointestinal conditions that require major abdominal surgery, pre and postoperatively. 4. To identify whether amino acid (protein) and/or arginine intake affect plasma ADMA levels in the post-operative period and to incorporate this outcome in future randomised controlled trials investigation arginine supplementation and other nutritional interventions. Parents of potential participants will be approached preoperatively or up to 5 days postoperatively to complete the informed consent process. Once the parents of potential participants have had sufficient time to read and process the information regarding the study (minimum 2 hours), and sufficient time to ask questions regarding the study, written consent will be obtained. Blood samples will be taken by the clinical team routinely as part of their clinical care. Patients will be managed as per accepted clinical practice and local clinical guidelines by the clinical team. There will be no changes from routine practice due to the SuNDiAL study. No extra blood tests will be taken for the SuNDiAL study. If an infant is eligible and the parents have given consent to participate in the SuNDiAL study, at the time of ordering routine clinical blood tests the clinical team will order an additional dummy blood test 'SUNDIAL store sample'. If there is any remaining serum following routine clinical blood tests, the 'SUNDIAL store sample' will alert the lab to store the blood sample for the SuNDiAL study. The sample will frozen and be stored in the SuNDiAL area of the research laboratory freezer in Alder Hey Children's Hospital. All samples with serum remaining will be stored. Samples will stop being stored once the patient is fully recovered or after 30 days post operatively which ever occurs first. The sample will be available for the clinical team to do further tests if these are required and this will take priority over testing the blood for research purposes. Once there is sufficient samples to run an analysis the samples with be transported to the research laboratory. The samples will then be analysed by the ELISA technique, to measure Arginine and ADMA. Samples will be anonymised by the research team prior to being transported to the Research Laboratory in the Institute in the park at Alder Hey Children hospital. The data will be anonymised prior to analysis. Data will be analysed for both the primary and secondary outcomes outlined above by the University of Liverpool Computational Biological Facility.

The study is aimed to clinically assess the AnovoTM Surgical System in ventral hernia procedures. Extensive preclinical testing of the system's integrity and safety has been performed to assure adequate safety for this trial.

Worldwide there is a lot of commotion about the effects and complications of various implants. In analogy to patients with silicone breast implants, some patients report various systemic complaints following inguinal polypropylene (PP) mesh implantation, suggesting 'Autoinflammatory/Autoimmunity Syndrome Induced by Adjuvants' (ASIA; Shoenfeld's syndrome) or some other suspected systemic auto-immune/inflammatory response. Although an evidence-based and causal relationship is lacking, patients report serious complaints. Therefore, the investigators recently started seeing these patients at the outpatient clinic and developed a diagnostic workup, including an elaborate anamnesis, conventional immunologic analyses and mesh allergy testing (MAT). Further, in case the implant is removed as part of the treatment due to a persistent wish of the patient, the PP explant will be histologically examined to find additional cues for an auto-immune/inflammatory response (and thus ASIA). So far, evidence on the optimal diagnostic workup for patients with suspected ASIA syndrome is lacking completely.