Histological Assessment of Wallerian Degeneration of the Rat Tibial Nerve Following Crush and Transection Injuries.

BACKGROUND: Wallerian degeneration (WD) following peripheral nerve injury (PNI) is an area of growing focus for pharmacological developments. Clinically, WD presents challenges in achieving full functional recovery following PNI, as prolonged denervation of distal tissues for an extended period of time can irreversibly destabilize sensory and motor targets with secondary tissue atrophy. Our objective is to improve upon histological assessments of WD. METHODS: Conventional methods utilize a qualitative system simply describing the presence or absence of WD in nerve fibers. We propose a three-category assessment that allows more quantification: A fibers appear normal, B fibers have moderate WD (altered axoplasm), and C fibers have extensive WD (myelin figures). Analysis was by light microscopy (LM) on semithin sections stained with toluidine blue in three rat tibial nerve lesion models (crush, partial transection, and complete transection) at 5 days postop and 5 mm distal to the injury site. The LM criteria were verified at the ultrastructural level. This early outcome measure was compared with the loss of extensor postural thrust and the absence of muscle atrophy. RESULTS: The results showed good to excellent internal consistency among counters, demonstrating a significant difference between the crush and transection lesion models. A significant decrease in fiber density in the injured nerves due to inflammation/edema was observed. The growth cones of regenerating axons were evident in the crush lesion group. CONCLUSION: The ABC method of histological assessment is a consistent and reliable method that will be useful to quantify the effects of different interventions on the WD process.

Extracorporeal Life Support for Cardiogenic Shock in Adult Congenital Heart Disease-An ELSO Registry Analysis.

There are minimal data on the use of venoarterial extracorporeal membrane life support (VA-ECLS) in adult congenital heart disease (ACHD) patients presenting with cardiogenic shock (CS). This study sought to describe the population of ACHD patients with CS who received VA-ECLS in the Extracorporeal Life Support Organization (ELSO) Registry. This was a retrospective analysis of adult patients with diagnoses of ACHD and CS in ELSO from 2009-2021. Anatomic complexity was categorized using the American College of Cardiology/American Heart Association 2018 guidelines. We described patient characteristics, complications, and outcomes, as well as trends in mortality and VA-ECLS utilization. Of 528 patients who met inclusion criteria, there were 32 patients with high-complexity anatomy, 196 with moderate-complexity anatomy, and 300 with low-complexity anatomy. The median age was 59.6 years (interquartile range, 45.8-68.2). The number of VA-ECLS implants increased from five implants in 2010 to 81 implants in 2021. Overall mortality was 58.3% and decreased year-by-year (ß= -2.03 [95% confidence interval, -3.36 to -0.70], p = 0.007). Six patients (1.1%) were bridged to heart transplantation and 21 (4.0%) to durable ventricular assist device. Complications included cardiac arrhythmia/tamponade (21.6%), surgical site bleeding (17.6%), cannula site bleeding (11.4%), limb ischemia (7.4%), and stroke (8.7%). Utilization of VA-ECLS for CS in ACHD patients has increased over time with a trend toward improvement in survival to discharge.

Compound Motor Action Potentials During a Modest Nerve Crush.

Nerve crush injury results in axonotmesis, characterized by disruption of axons and their myelin sheaths with relative sparing of the nerve's connective tissue. Despite the widespread use of crush injury models, no standardized method for producing these lesions has been established. We characterize a crush model in which a narrow forceps is used to induce a modest and controlled compressive injury. The instantaneous compound motor action potential (CMAP) is monitored in situ and in real-time, allowing the characterization of neuromuscular response during and after injury. The tibial nerves of 11 anesthetized rats were surgically isolated. After the placement of electrodes, CMAPs were elicited and registered using a modular-data-acquisition system. Dumont-#5 micro-forceps were instrumented with a force transducer allowing force measurement via a digital sensor. Baseline CMAPs were recorded prior to crush and continued for the duration of the experiment. Nerve crushing commenced by gradually increasing the force applied to the forceps. At a target decrease in CMAP amplitude of 70%-90%, crushing was halted. CMAPs were continually recorded for 5-20 min after the termination of the crushing event. Nerves were then fixed for histological assessment. The following post-crush mean values from 19 trials were reported: peak CMAP amplitude decreased by 81.6% from baseline, duration of crush was 17 sec, rate of applied force was 0.03 N/sec, and maximal applied force was 0.5 N. A variety of agonal phenomena were evident post-lesion. Following the initial decrease in CMAP, 8 of 19 trials demonstrated a partial and transient recovery, followed by a further decline. Thirteen trials exhibited a CMAP amplitude near zero at the end of the recording. Twelve trials demonstrated a superimposed EMG background response during and after the crush event, with disappearance occurring within 4-8 min. Qualitative histology assessment at the lesion site demonstrated a correspondence between CMAP response and partial sparing of nerve fibers. By using a targeted decline in CMAP amplitude as the endpoint, researchers may be able to produce controlled, brief, and reproducible crush injuries. This model can also be used to test interventions aimed at enhancing subsequent regeneration and behavioral recovery.

Incarcerated diaphragmatic hernia with intrathoracic bowel obstruction after right liver donation.

Liver transplantation has become an acceptable surgical procedure with the advancement of the technical and rejection considerations involved. Initially nonliving donors were used for transplantation procedures. However, with improved techniques, living donor procedures have become much more frequent. With this, complications involving the transplant organ donor may occur. We present 2 patients with intrathoracic bowel obstruction due to herniation of the small intestine and colon through a defect in the dome of the diaphragm with development of chest pain and gastrointestinal symptoms. Both patients were diagnosed by computerized tomography scan and had a right thoracotomy with lysis of the adhesions, reduction of the hernia, repair of the diaphragm, and mesh reinforcement of the diaphragm. Neither patient had a prior diaphragm defect. These patients, on review of the literature, represent the first 2 such reported cases and suggest the need to be aware of any potential diaphragm defects before closure of the abdomen after resection of the donor liver or if they develop appropriate symptomatology.

Advances in the Formulation and Assembly of Non-Cationic Lipid Nanoparticles for the Medical Application of Gene Therapeutics.

Lipid nanoparticles have become increasingly popular delivery platforms in the field of gene therapy, but bench-to-bedside success has been limited. Many liposomal gene vectors are comprised of synthetic cationic lipids, which are associated with lipid-induced cytotoxicity and immunogenicity. Natural, non-cationic PEGylated liposomes (PLPs) demonstrate favorable biocompatibility profiles but are not considered viable gene delivery vehicles due to inefficient nucleic acid loading and reduced cellular uptake. PLPs can be modified with cell-penetrating peptides (CPPs) to enhance the intracellular delivery of liposomal cargo but encapsulate leakage upon CPP-PLP assembly is problematic. Here, we aimed to identify parameters that overcome these performance barriers by incorporating nucleic acid condensers during CPP-PLP assembly and screening variable ethanol injection parameters for optimization. CPP-PLPs were formed with R8-amphiphiles via pre-insertion, post-insertion and post-conjugation techniques and liposomes were characterized for size, surface charge, homogeneity, siRNA encapsulation efficiency and retention and cell associative properties. Herein we demonstrate that pre-insertion of stearylated R8 into PLPs is an efficient method to produce non-cationic CPP-PLPs and we provide additional assembly parameter specifications for a modified ethanol injection technique that is optimized for siRNA encapsulation/retention and enhanced cell association. This assembly technique could provide improved clinical translation of liposomal based gene therapy applications.

Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions.

Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. Here, we present the progress in the development of targeted liposomal nanocarriers designed for preferential collagen IV binding under simulated static vascular flow conditions. PEGylated liposomes (PLPs), previously established as effective delivery systems in vascular cells types, served as non-targeting controls. Collagen-targeting liposomes (CT-PLPs) were formed by conjugating established collagen-binding peptides to modified lipid heads via click chemistry (CTL), and inserting them at varying mol% either at the time of PLP assembly or via micellar transfer. All groups included fluorescently labeled lipid species for imaging and quantification. Liposomes were exposed to collagen IV matrices statically or via hemodynamic flow, and binding was measured via fluorometric analyses. CT-PLPs formed with 5 mol% CTL at the time of assembly demonstrated the highest binding affinity to collagen IV under static conditions, while maintaining a nanoparticle characterization profile of ~50 nm size and a homogeneity polydispersity index (PDI) of ~0.2 favorable for clinical translation. When liposomes were exposed to collagen matrices within a pressurized flow system, empirically defined CT-PLPs demonstrated significant binding at shear stresses mimetic of physiological through pathological conditions in both the venous and arterial architectures. Furthermore, when human saphenous vein explants were perfused with liposomes within a closed bioreactor system, CT-PLPs demonstrated significant ex vivo binding to diseased vascular tissue. Ongoing studies aim to further develop CT-PLPs for controlled targeting in a rodent model of vascular injury. The CT-PLP nanocarriers established here show promise as the framework for a spatially controlled delivery platform for future application in targeted vascular therapeutics.

Cactus Spine Wounds: A Case Report and Short Review of the Literature.

INTRODUCTION: Cactus plants are commonly seen in arid southwestern regions of the United States. Due to their ready availability, they have become a popular houseplant. The spines or glochidia can easily puncture the skin with only minor pressure (ie, bumping or touching the cactus). Removal of the offending spine is difficult, even with tweezers. CASE: An 18-year-old woman initially self-removed the spines, and marked discomfort and intense erythematous reaction developed within 8 to 10 hours. Patient presented to the emergency room at Mercy Hospital and Trauma Center (Janesville, Wisconsin), where spine removal was unsuccessful. RESULTS: Following emergency room discharge, she had difficulty walking from pain and swelling and was advised to use heat packs, take amoxicillin/clavulanic acid, and rest with her leg elevated for another 7 days along with using eye drops for eye irritation. The lesions slowly improved over the next several months. CONCLUSION: The case of multiple barrel cactus spine injuries with severe pain and swelling is presented herein as well as a review of the treatment options and complications of cactus spine injuries.

Malignant and benign thoracic tumors during pregnancy.

Eight female patients 23-38 years of age are presented who were pregnant and had concomitant thoracic tumors. The tumors were of a variety of cell types, both malignant and benign, causing chest pain, dyspnea, shock, hemoptysis, and mass formation. Surgical intervention, cobalt radiation, and chemotherapy led to survival and cure of both the mothers and the children. An aggressive approach is recommended.

Remote surgicenter experience with hernia repair.

A remote outpatient surgicenter was planned and constructed with three partner groups-76 physicians and two competing hospitals. The CFS was opened in July 1994 and has since performed a large volume of procedures: >124,800 total and, in 2003, 14,900 cases. This multispecialty center during that same period of time (1994 to date) has performed 2659 hernia operations. Patients were discharged home in 1-2 hours after surgery to be followed as outpatients in the physician's office. Only six patients were admitted to the hospital. This efficient and economic model is well suited for hernia repair in the selected adult and pediatric patient population without a significant number of adverse events. The community has readily accepted this program for adult and pediatric hernia repair. Patients, family members, referring physicians, and participating physicians have endorsed and recommended the program.

Tracheobronchial tumor resection.

Primary tracheobronchial nonbronchogenic carcinoma tumors are uncommon. The presence of these tumors may cause asthmatic-like symptoms and marked respiratory distress. When seen, the patients are usually very apprehensive and present difficult decisions regarding treatment and surgery, especially with regard to anesthetic considerations. We are reporting our experience with these tumors in the community hospital. A number of patients are presented, including 1) a tracheal tumor during pregnancy, 2) a tracheobronchial tumor cast, and 3) a carinal resection. All resected patients did well with long-term survival.

Giant mediastinal parathyroid adenoma with hypercalcemia.

Parathyroid disease is uncommon, but when found it is always of interest to the physician. Most patients with parathyroid disease also have hypercalcemia. Benign adenomatous disease is the most frequent surgical parathyroid lesion seen. Most of these lesions occur in the neck and are usually <2 cm in diameter. We report the case of a 50-year-old patient with familial neurofibromatosis, a serum calcium of 19 mg/dl, nephrocalcinosis, and renal failure. Evaluation revealed a large (5.7 x 4.5 x 2.9-cm) mediastinal adenoma. At resection, the tumor weighed 39.5 g. Symptomatology rapidly improved postoperatively.

Endovascular repair of aortojejunal fistula.

A 64-year-old male with vascular occlusive disease involving multiple vessels is presented with a history of aortobifemoral bypass grafting and bilateral femoral false aneurysm surgery. More recently, he had cystectomy for bladder carcinoma and repeated urinary stents and sepsis. Gastrointestinal bleeding developed due to the aortic graft anastomotic false aneurysm eroding into the distal jejunum. Endograft placement stabilized the critical situation and served as a bridge to a safer, more elective resection of the previous graft, the false aneurysm, and the endograft with closure of the jejunum.

Prosthetic heart valve thrombosis: an overview.

BACKGROUND: Valvular heart disease represents a significant burden to patients with cardiovascular diseases. Surgical treatment of diseased heart valves represents a significant advancement for these patients. However, there are specific complications related to prosthetic valves, including valve thrombosis. METHODS: Review article. RESULTS: Thrombosis of a prosthetic heart valve can present with gradual cardiac decline, embolic phenomena, or frank cardiogenic shock. The diagnosis of prosthetic valve thrombosis is by history, physical examination, and by an imaging modality. Treatment of the thrombosed valve is either surgical or with thrombolysis. Both modalities have significant morbidity and mortality. CONCLUSION: Treatment of valvular heart disease does not remove the patient from significant risks. Inherent to a prosthetic heart valve is the risk for valvular thrombosis. Prompt recognition and treatment of prosthetic valve thrombosis is important.