Postoperative Imaging of Endometriosis.

Endometriosis is a highly prevalent disease that affects 10%-15% of women of reproductive age worldwide and is mainly associated with chronic pelvic pain and infertility. With the widespread use of imaging for the diagnosis and monitoring of endometriosis, combined with the ability of surgery to eradicate the disease and address infertility, there has been a significant increase in recent years in imaging examinations for postoperative evaluation of endometriosis. US and MRI are used not only to help diagnose and map endometriosis but also to evaluate refractory symptoms, residual lesions, and complications at posttreatment assessment. Knowledge of surgical techniques and recognition of expected postoperative imaging findings are crucial to differentiate postoperative changes from residual disease and/or recurrence. The authors discuss imaging aspects of postoperative endometriosis, with an emphasis on the imaging approach, comprehension of surgical techniques, recognition of the expected findings, possible complications, and analysis of residual disease or recurrence. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by VanBuren in this issue. The slide presentation from the RSNA Annual Meeting is available for this article.

Axonal Tract Reconstruction Using a Tissue-Engineered Nigrostriatal Pathway in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) affects 1-2% of people over 65, causing significant morbidity across a progressive disease course. The classic PD motor deficits are caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in the loss of their long-distance axonal projections that modulate striatal output. While contemporary treatments temporarily alleviate symptoms of this disconnection, there is no approach able to replace the nigrostriatal pathway. We applied microtissue engineering techniques to create a living, implantable tissue-engineered nigrostriatal pathway (TE-NSP) that mimics the architecture and function of the native pathway. TE-NSPs comprise a discrete population of dopaminergic neurons extending long, bundled axonal tracts within the lumen of hydrogel micro-columns. Neurons were isolated from the ventral mesencephalon of transgenic rats selectively expressing the green fluorescent protein in dopaminergic neurons with subsequent fluorescent-activated cell sorting to enrich a population to 60% purity. The lumen extracellular matrix and growth factors were varied to optimize cytoarchitecture and neurite length, while immunocytochemistry and fast-scan cyclic voltammetry (FSCV) revealed that TE-NSP axons released dopamine and integrated with striatal neurons in vitro. Finally, TE-NSPs were implanted to span the nigrostriatal pathway in a rat PD model with a unilateral 6-hydroxydopamine SNpc lesion. Immunohistochemistry and FSCV established that transplanted TE-NSPs survived, maintained their axonal tract projections, extended dopaminergic neurites into host tissue, and released dopamine in the striatum. This work showed proof of concept that TE-NSPs can reconstruct the nigrostriatal pathway, providing motivation for future studies evaluating potential functional benefits and long-term durability of this strategy. This pathway reconstruction strategy may ultimately replace lost neuroarchitecture and alleviate the cause of motor symptoms for PD patients.

Pharmacokinetic and Pharmacological Aspects of a Papain-Based Enzyme Solution for Rescuing Clogged Enteral Feeding Tubes.

Successful enteral feeding depends on patent enteral feeding tubes to permit trouble-free entry of nutritional formula into the alimentary tract. However, tube clogs can be a challenging complication of enteral feeding. This report addresses questions about using a papain-based enzyme solution to unclog enteral feeding tubes, including any effects that papain may have on patients and if solution use should be contraindicated in patients on ketogenic diets. The gastrointestinal tract is not permissive for significant papain activity and papain absorbed into the blood would likely be neutralized by antiproteases. In vitro examinations do not suggest toxic effects of papain in vivo, and those recognized in the latter setting are due to papain loads that exceed those used to unclog enteral feeding tubes. Allergies to papain occur infrequently and are probably attributable to an immunoglobulin E-mediated reaction to this enzyme. Although the amount of carbohydrate consumed upon single use of the unclogging solution is very low, a provider should decide whether using the papain-based enzyme solution for enteral feeding purposes is appropriate in patients who practice ketogenic diets. The benefits of using the papain-based enzyme solution to unclog enteral feeding tubes appear to outweigh any risks associated with its use.

Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study.

BACKGROUND: The ALEX study demonstrated significantly improved progression-free survival (PFS) with alectinib versus crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC) at the primary data cut-off (9 February 2017). We report mature PFS (cut-off: 30 November 2018) and overall survival (OS) data up to 5 years (cut-off: 29 November 2019). PATIENTS AND METHODS: Patients with stage III/IV ALK-positive NSCLC were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151) until disease progression, toxicity, withdrawal or death. Primary end point: investigator-assessed PFS. Secondary end points included objective response rate, OS and safety. RESULTS: Mature PFS data showed significantly prolonged investigator-assessed PFS with alectinib [hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.32-0.58; median PFS 34.8 versus 10.9 months crizotinib]. Median duration of OS follow-up: 48.2 months alectinib, 23.3 months crizotinib. OS data remain immature (37% of events). Median OS was not reached with alectinib versus 57.4 months with crizotinib (stratified HR 0.67, 95% CI 0.46-0.98). The 5-year OS rate was 62.5% (95% CI 54.3-70.8) with alectinib and 45.5% (95% CI 33.6-57.4) with crizotinib, with 34.9% and 8.6% of patients still on study treatment, respectively. The OS benefit of alectinib was seen in patients with central nervous system metastases at baseline [HR 0.58 (95% CI 0.34-1.00)] and those without [HR 0.76 (95% CI 0.45-1.26)]. Median treatment duration was longer with alectinib (28.1 versus 10.8 months), and no new safety signals were observed. CONCLUSIONS: Mature PFS data from ALEX confirmed significant improvement in PFS for alectinib over crizotinib in ALK-positive NSCLC. OS data remain immature, with a higher 5-year OS rate with alectinib versus crizotinib. This is the first global randomized study to show clinically meaningful improvement in OS for a next-generation tyrosine kinase inhibitor versus crizotinib in treatment-naive ALK-positive NSCLC. CLINICAL TRIALS NUMBER: NCT02075840.

Simulation System of Electric-Powered Wheelchairs for Training Purposes.

For some people with severe physical disabilities, the main assistive device to improve their independence and to enhance overall well-being is an electric-powered wheelchair (EPW). However, there is a necessity to offer users EPW training. In this work, the Simcadrom is introduced, which is a virtual reality simulator for EPW driving learning purposes, testing of driving skills and performance, and testing of input interfaces. This simulator uses a joystick as the main input interface, and a virtual reality head-mounted display. However, it can also be used with an eye-tracker device as an alternative input interface and a projector to display the virtual environment (VE). Sense of presence, and user experience questionnaires were implemented to evaluate this version of the Simcadrom in addition to some statistical tests for performance parameters like: total elapsed time, path following error, and total number of commands. A test protocol was proposed and, considering the overall results, the system proved to simulate, very realistically, the usability, kinematics, and dynamics of a real EPW in a VE. Most subjects were able to improve their EPW driving performance in the training session. Furthermore, all skills learned are feasible to be transferred to a real EPW.

Fibrin glue as a stabilization strategy in peripheral nerve repair when using porous nerve guidance conduits.

Porous conduits provide a protected pathway for nerve regeneration, while still allowing exchange of nutrients and wastes. However, pore sizes >30 µm may permit fibrous tissue infiltration into the conduit, which may impede axonal regeneration. Coating the conduit with Fibrin Glue (FG) is one option for controlling the conduit's porosity. FG is extensively used in clinical peripheral nerve repair, as a tissue sealant, filler and drug-delivery matrix. Here, we compared the performance of FG to an alternative, hyaluronic acid (HA) as a coating for porous conduits, using uncoated porous conduits and reverse autografts as control groups. The uncoated conduit walls had pores with a diameter of 60 to 70 µm that were uniformly covered by either FG or HA coatings. In vitro, FG coatings degraded twice as fast as HA coatings. In vivo studies in a 1 cm rat sciatic nerve model showed FG coating resulted in poor axonal density (993 ± 854 #/mm2), negligible fascicular area (0.03 ± 0.04 mm2), minimal percent wet muscle mass recovery (16 ± 1 in gastrocnemius and 15 ± 5 in tibialis anterior) and G-ratio (0.73 ± 0.01). Histology of FG-coated conduits showed excessive fibrous tissue infiltration inside the lumen, and fibrin capsule formation around the conduit. Although FG has been shown to promote nerve regeneration in non-porous conduits, we found that as a coating for porous conduits in vivo, FG encourages scar tissue infiltration that impedes nerve regeneration. This is a significant finding considering the widespread use of FG in peripheral nerve repair.

Dual-Component Gelatinous Peptide/Reactive Oligomer Formulations as Conduit Material and Luminal Filler for Peripheral Nerve Regeneration.

Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility. Second, cGEL was reformulated as injectable shear thinning filler for established NGCs, here tyrosine-derived polycarbonate-based braided conduits. Thereby, the formulation contained the small molecule LM11A-31. The biofunctionalized cGEL filler was assessed regarding building block integration, mechanical properties, in vitro cytotoxicity, and growth permissive effects on human adipose tissue-derived stem cells. A positive in vitro evaluation motivated further application of the filler material in a sciatic nerve defect. Compared to the empty conduit and pristine cGEL, the functionalization performed superior, though the autologous nerve graft remains the gold standard. In conclusion, LM11A-31 functionalized cGEL filler with extracellular matrix (ECM)-like characteristics and specific biochemical cues holds great potential to support PNR.

Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance.

OBJECTIVE: Notch signaling has been identified as a critical regulator in cartilage development and joint maintenance, and loss of Notch signaling in all joint tissues results in an early and progressive osteoarthritis (OA)-like pathology. This study investigated the targeted cell population within the knee joint in which Notch signaling is required for normal cartilage and joint integrity. METHODS: Two loss-of-function mouse models were generated with tissue-specific knockout of the core Notch signaling component, RBPjκ. The AcanCre(ERT2) transgene specifically removed Rbpjκ floxed alleles in postnatal joint chondrocytes, while the Col1Cre(2.3kb) transgene deleted Rbpjκ in osteoblast populations, including subchondral osteoblasts. Mutant and control mice were analyzed via histology, immunohistochemistry (IHC), real-time quantitative polymerase chain reaction (qPCR), X-ray, and microCT imaging at multiple time-points. RESULTS: Loss of Notch signaling in postnatal joint chondrocytes results in a progressive OA-like pathology, and triggered the recruitment of non-targeted fibrotic cells into the articular cartilage potentially due to mis-regulated chemokine expression from within the cartilage. Upon recruitment, these fibrotic cells produced degenerative enzymes that may lead to the observed cartilage degradation and contribute to a significant portion of the age-related OA-like pathology. On the contrary, loss of Notch signaling in subchondral osteoblasts did not affect normal cartilage development or joint maintenance. CONCLUSIONS: RBPjκ-dependent Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance.

Imaging Manifestations of Hematologic Diseases with Renal and Perinephric Involvement.

The kidneys and perinephric tissues can be affected by a variety of hematologic disorders, which usually occur in the setting of multisystem involvement. In many of these disorders, imaging is used to evaluate the extent of disease, guide biopsy, and/or monitor disease activity and patient response to therapy. Lymphoma, leukemia, and multiple myeloma commonly manifest as multiple parenchymal or perinephric lesions. Erdheim-Chester disease and Rosai-Dorfman disease, rare forms of multisystemic histiocytosis, are often identified as perinephric and periureteral masses. Renal abnormalities depicted at imaging in patients with sickle cell disease include renal enlargement, papillary necrosis, and renal medullary carcinoma. Sickle cell disease, along with other causes of intravascular hemolysis, can also lead to hemosiderosis of the renal cortex. Thrombosis of renal veins is sometimes seen in patients with coagulation disorders but more often occurs in association with certain malignancies and nephrotic syndrome. Immunoglobulin G4-related sclerosing disease is another multisystem process that often produces focal renal lesions, seen along with involvement of more characteristic organs such as the pancreas. Perinephric lesions with calcifications should raise the possibility of secondary amyloidosis, especially in patients with a history of lymphoma and multiple myeloma. Although the imaging patterns of renal and perinephric involvement are usually not specific for a single entity, and the same entity can manifest with different or overlapping patterns, familiarity with these patterns and key clinical and histopathologic features may help to narrow the differential diagnosis and determine the next step of care. (©)RSNA, 2016.

Modeling the Insertion Mechanics of Flexible Neural Probes Coated with Sacrificial Polymers for Optimizing Probe Design.

Single-unit recording neural probes have significant advantages towards improving signal-to-noise ratio and specificity for signal acquisition in brain-to-computer interface devices. Long-term effectiveness is unfortunately limited by the chronic injury response, which has been linked to the mechanical mismatch between rigid probes and compliant brain tissue. Small, flexible microelectrodes may overcome this limitation, but insertion of these probes without buckling requires supporting elements such as a stiff coating with a biodegradable polymer. For these coated probes, there is a design trade-off between the potential for successful insertion into brain tissue and the degree of trauma generated by the insertion. The objective of this study was to develop and validate a finite element model (FEM) to simulate insertion of coated neural probes of varying dimensions and material properties into brain tissue. Simulations were performed to predict the buckling and insertion forces during insertion of coated probes into a tissue phantom with material properties of brain. The simulations were validated with parallel experimental studies where probes were inserted into agarose tissue phantom, ex vivo chick embryonic brain tissue, and ex vivo rat brain tissue. Experiments were performed with uncoated copper wire and both uncoated and coated SU-8 photoresist and Parylene C probes. Model predictions were found to strongly agree with experimental results (<10% error). The ratio of the predicted buckling force-to-predicted insertion force, where a value greater than one would ideally be expected to result in successful insertion, was plotted against the actual success rate from experiments. A sigmoidal relationship was observed, with a ratio of 1.35 corresponding to equal probability of insertion and failure, and a ratio of 3.5 corresponding to a 100% success rate. This ratio was dubbed the "safety factor", as it indicated the degree to which the coating should be over-designed to ensure successful insertion. Probability color maps were generated to visually compare the influence of design parameters. Statistical metrics derived from the color maps and multi-variable regression analysis confirmed that coating thickness and probe length were the most important features in influencing insertion potential. The model also revealed the effects of manufacturing flaws on insertion potential.

Coating flexible probes with an ultra fast degrading polymer to aid in tissue insertion.

We report a fabrication process for coating neural probes with an ultrafast degrading polymer to create consistent and reproducible devices for neural tissue insertion. The rigid polymer coating acts as a probe insertion aid, but resorbs within hours post-implantation. Despite the feasibility for short term neural recordings from currently available neural prosthetic devices, most of these devices suffer from long term gliosis, which isolates the probes from adjacent neurons, increasing the recording impedance and stimulation threshold. The size and stiffness of implanted probes have been identified as critical factors that lead to this long term gliosis. Smaller, more flexible probes that match the mechanical properties of brain tissue could allow better long term integration by limiting the mechanical disruption of the surrounding tissue during and after probe insertion, while being flexible enough to deform with the tissue during brain movement. However, these small flexible probes inherently lack the mechanical strength to penetrate the brain on their own. In this work, we have developed a micromolding method for coating a non-functional miniaturized SU-8 probe with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)). Coated, non-functionalized probes of varying dimensions were reproducibly fabricated with high yields. The polymer erosion/degradation profiles of the probes were characterized in vitro. The probes were also mechanically characterized in ex vivo brain tissue models by measuring buckling and insertion forces during probe insertion. The results demonstrate the ability to produce polymer coated probes of consistent quality for future in vivo use, for example to study the effects of different design parameters that may affect tissue response during long term chronic intra-cortical microelectrode neural recordings.

The overwhelming use of rat models in nerve regeneration research may compromise designs of nerve guidance conduits for humans.

Rats are not the best model for the evolving complexities we face in designing nerve repair strategies today. The development of effective nerve guidance conduits for nerve regeneration is severely limited by the rat sciatic nerve model as the almost exclusive research model in academia. An immense effort is underway to develop an alternative to autologous nerve grafts for the repair of nerve defects, aiming particularly at larger gap repairs of 5-30 cm or more. This must involve combinations of ever more complex components, which in the vast majority of cases begin their testing in the rat model. Three major problems are at play: (1) The majority of nerve regeneration data is now being generated in the rat, which is likely to skew treatment outcomes and lead to inappropriate evaluation of risks and benefits. (2) The rat is a particularly poor model for the repair of human critical gap defects due to both its small size and its species-specific neurobiological regenerative profile. (3) Translation from rat to human has proven unreliable for nerve regeneration, as for many other applications. We explore each of these facets and their implications, in order to highlight the need for appropriate awareness in animal model selection when translating nerve regeneration modalities of ever-increasing complexity-from relatively simple devices to drug-device-biologic combinations.

Benign and malignant tumors of the rectum and perirectal region.

Although most rectal masses are histologically characterized as adenocarcinomas, the rectum and perirectal region can be affected by a wide variety of tumors and tumor-like conditions that can mimic the symptoms caused by rectal adenocarcinoma, including mucosal or submucosal rectal tumors such as lymphoma, gastrointestinal stromal tumor, leiomyosarcoma, neuroendocrine tumor, hemangioma, and melanoma, as well as tumors of the perirectal region such as developmental cyst, neurogenic tumor, osseous tumor, and other miscellaneous conditions. As a group, tumors of the rectum are considerably different from the group of tumors that arise in the perirectal region: they are most often neoplastic, symptomatic, and malignant, whereas tumors arising in the perirectal region are most commonly congenital, asymptomatic, and benign. Proctoscopy with biopsy is the most important method for the diagnosis of rectal tumors, but this procedure cannot determine the precise intramural extension of a rectal tumor and cannot accurately distinguish submucosal and intramural tumors from extramural tumors. Cross-sectional imaging, especially transrectal ultrasound and magnetic resonance imaging, allows evaluation of the entire bowel wall thickness and the perirectal tissues, helping further characterize these tumors. Recognition of the existence of these masses and their key clinical and imaging features is crucial for clinicians to accurately diagnose and appropriately manage these conditions.

Clinical trial outcomes of high- and extra high-profile breast implants.

BACKGROUND: Clinical data concerning potential risks and benefits associated with the use of high- and extra high-profile breast implants are lacking. OBJECTIVES: The authors assess the risk of adverse events (AE) with high- and extra high-profile breast implants compared with low- to moderate-profile breast implants in patients enrolled in long-term clinical studies. METHODS: Relative risks (RR) of capsular contracture (CC), moderate to severe malposition, and secondary procedure were calculated using Cox proportional hazards regression, adjusting for patient, procedure, and device characteristics among patients enrolled in the primary augmentation cohorts of the Core (NCT00689871; round, silicone-filled implants) and 410 (NCT00690339; shaped, highly cohesive silicone-filled implants) clinical studies. Study pooling provided comparisons of implant shape and fill, as well as contributed to relative outcome. Analyses were also stratified by preoperative breast measures. RESULTS: In the Core study (N = 454; 907 implants; mean follow-up 7.2 years; 3669 person-years), and the combined Core and 410 studies (N = 4412; 8811 implants; mean follow-up 3.0 years; 14 528 person-years), risk of CC, secondary procedures, and mastopexy as a secondary procedure were reduced in high-profile versus low- to moderate-profile breast implants (P < .05). The risk of moderate to severe malposition was not significantly different between high-profile and low- to moderate-profile breast implants in the Core or combined studies (RR, 0.58 [95% confidence interval (CI), 0.22-1.51] and RR, 0.72 [95% CI, 0.31-1.70], respectively). Analyses stratified by preoperative breast measures did not indicate higher risk of CC, malposition, or secondary procedure among patients with either smaller (<17 cm) or larger (≥17 cm) preoperative measures. CONCLUSIONS: Among primary augmentation patients with round, silicone-filled, or shaped, highly cohesive silicone-filled implants, high- and extra high-profile implants were associated with lower risks of CC, secondary procedures, and mastopexy and were not associated with greater risks of moderate to severe malposition versus low- to moderate-profile implants. LEVEL OF EVIDENCE: 3.

LI-RADS: a case-based review of the new categorization of liver findings in patients with end-stage liver disease.

Hepatocellular carcinoma (HCC) is a global health problem, with the burden of disease expected to increase in the coming years. Patients who are at increased risk for developing HCC undergo routine imaging surveillance, and once a focal abnormality is detected, evaluation with multiphasic contrast material-enhanced computed tomography or magnetic resonance imaging is necessary for diagnosis and staging. Currently, findings at liver imaging are inconsistently interpreted and reported by most radiologists. The Liver Imaging-Reporting and Data System (LI-RADS) is an initiative supported by the American College of Radiology that aims to reduce variability in lesion interpretation by standardizing report content and structure; improving communication with clinicians; and facilitating decision making (eg, for transplantation, ablative therapy, or chemotherapy), outcome monitoring, performance auditing, quality assurance, and research. Five categories that follow the diagnostic thought process are used to stratify individual observations according to the level of concern for HCC, with the most worrisome imaging features including a masslike configuration, arterial phase hyperenhancement, portal venous phase or later phase hypoenhancement, an increase of 10 mm or more in diameter within 1 year, and tumor within the lumen of a vein. LI-RADS continues to evolve and is expected to integrate a series of improvements in future versions that will positively affect the care of at-risk patients.

A method for assessing and monitoring consistency of nonclinical ECG analysis.

Cardiovascular safety is a key area of concern for new drugs in development, and the collection and analysis of electrocardiograms (ECGs) is a standard and major component of nonclinical testing. Digital data capture technology allows for high-throughput and long-duration ECG collections, resulting in large volumes of data. Consistent analysis of these ECG data is critical for detecting meaningful changes during nonclinical drug development. We developed a method to assess the consistency of nonclinical ECG analysis for a group of analysts over time. Eight­lead ECGs were collected from conscious dogs using Ponemah (v5.2, DSI). Analysts placed Pstart, Qstart, Rpeak, Send, and Tend marks on six waveforms for each animal. The ECG files were randomized and re-marked under blinded conditions 4 to 14 days following initial mark placement. Averages of each parameter measured (RR interval, QRS duration, PR interval, and QT interval) were compiled for each marking session and analyst. A Gage R&R evaluation was completed. Graphical output from the Gage R&R evaluation showed distinct variability on group and individual analyst levels. Differences in inter- and intra-analyst variability (reproducibility and repeatability, respectively) were observed between trained analysts and analysts in training. The Gage R&R method is an effective tool for assessing consistency of digital ECG mark placement at a group level. Furthermore, it is able to identify areas of improvement for individual ECG analysts and to assess ECG analyst consistency during their training period. The assessment results are useful for facilitating discussions on best practices and maintaining consistency of mark placement.

Tissue-engineered grafts exploit axon-facilitated axon regeneration and pathway protection to enable recovery after 5-cm nerve defects in pigs.

Functional restoration following major peripheral nerve injury (PNI) is challenging, given slow axon growth rates and eventual regenerative pathway degradation in the absence of axons. We are developing tissue-engineered nerve grafts (TENGs) to simultaneously "bridge" missing nerve segments and "babysit" regenerative capacity by providing living axons to guide host axons and maintain the distal pathway. TENGs were biofabricated using porcine neurons and "stretch-grown" axon tracts. TENG neurons survived and elicited axon-facilitated axon regeneration to accelerate regrowth across both short (1 cm) and long (5 cm) segmental nerve defects in pigs. TENG axons also closely interacted with host Schwann cells to maintain proregenerative capacity. TENGs drove regeneration across 5-cm defects in both motor and mixed motor-sensory nerves, resulting in dense axon regeneration and electrophysiological recovery at levels similar to autograft repairs. This approach of accelerating axon regeneration while maintaining the pathway for long-distance regeneration may achieve recovery after currently unrepairable PNIs.

Beyond appendicitis: common and uncommon gastrointestinal causes of right lower quadrant abdominal pain at multidetector CT.

Right lower quadrant abdominal pain is one of the most common causes of a patient visit to the emergency department. Although appendicitis is the most common condition requiring surgery in patients with abdominal pain, right lower quadrant pain can be indicative of a vast list of differential diagnoses and is thus a challenge for clinicians. Other causes of right lower quadrant pain beyond appendicitis include inflammatory and infectious conditions involving the ileocecal region; diverticulitis; malignancies; conditions affecting the epiploic appendages, omentum, and mesentery; and miscellaneous conditions. Multidetector computed tomography (CT) has emerged as the modality of choice for evaluation of patients with several acute traumatic and nontraumatic conditions causing right lower quadrant pain. Multidetector CT is an extremely useful noninvasive method for diagnosis and management of not only the most common causes such as appendicitis but also less common conditions.

Tyrosine-derived polycarbonate nerve guidance tubes elicit proregenerative extracellular matrix deposition when used to bridge segmental nerve defects in swine.

Promising biomaterials should be tested in appropriate large animal models that recapitulate human inflammatory and regenerative responses. Previous studies have shown tyrosine-derived polycarbonates (TyrPC) are versatile biomaterials with a wide range of applications across multiple disciplines. The library of TyrPC has been well studied and consists of thousands of polymer compositions with tunable mechanical characteristics and degradation and resorption rates that are useful for nerve guidance tubes (NGTs). NGTs made of different TyrPCs have been used in segmental nerve defect models in small animals. The current study is an extension of this work and evaluates NGTs made using two different TyrPC compositions in a 1 cm porcine peripheral nerve repair model. We first evaluated a nondegradable TyrPC formulation, demonstrating proof-of-concept chronic regenerative efficacy up to 6 months with similar nerve/muscle electrophysiology and morphometry to the autograft repair control. Next, we characterized the acute regenerative response using a degradable TyrPC formulation. After 2 weeks in vivo, TyrPC NGT promoted greater deposition of pro-regenerative extracellular matrix (ECM) constituents (in particular collagen I, collagen III, collagen IV, laminin, and fibronectin) compared to commercially available collagen-based NGTs. This corresponded with dense Schwann cell infiltration and axon extension across the lumen. These findings confirmed results reported previously in a mouse model and reveal that TyrPC NGTs were well tolerated in swine and facilitated host axon regeneration and Schwann cell infiltration in the acute phase across segmental defects - likely by eliciting a favorable neurotrophic ECM milieu. This regenerative response ultimately can contribute to functional recovery.

Tissue engineered axon-based "living scaffolds" promote survival of spinal cord motor neurons following peripheral nerve repair.

Peripheral nerve injury (PNI) impacts millions annually, often leaving debilitated patients with minimal repair options to improve functional recovery. Our group has previously developed tissue engineered nerve grafts (TENGs) featuring long, aligned axonal tracts from dorsal root ganglia (DRG) neurons that are fabricated in custom bioreactors using the process of axon "stretch-growth." We have shown that TENGs effectively serve as "living scaffolds" to promote regeneration across segmental nerve defects by exploiting the newfound mechanism of axon-facilitated axon regeneration, or "AFAR," by simultaneously providing haptic and neurotrophic support. To extend this work, the current study investigated the efficacy of living versus nonliving regenerative scaffolds in preserving host sensory and motor neuronal health following nerve repair. Rats were assigned across five groups: naïve, or repair using autograft, nerve guidance tube (NGT) with collagen, NGT + non-aligned DRG populations in collagen, or TENGs. We found that TENG repairs yielded equivalent regenerative capacity as autograft repairs based on preserved health of host spinal cord motor neurons and acute axonal regeneration, whereas NGT repairs or DRG neurons within an NGT exhibited reduced motor neuron preservation and diminished regenerative capacity. These acute regenerative benefits ultimately resulted in enhanced levels of functional recovery in animals receiving TENGs, at levels matching those attained by autografts. Our findings indicate that TENGs may preserve host spinal cord motor neuron health and regenerative capacity without sacrificing an otherwise uninjured nerve (as in the case of the autograft) and therefore represent a promising alternative strategy for neurosurgical repair following PNI.