Spigelian Hernia: A Case report.

A Spigelian hernia is a hernia through the Spigelian fascia which are difficult to diagnose as they do not present with a subcutaneous swelling and can be dangerous as there is a high risk of incarceration. We report a case of a 51-year-old female who presented to our surgical unit with epigastric pain for 5 days. She was diagnosed with Spigelian hernia with esophagitis and antral gastritis with the help of a computed tomography scan and upper gastrointestinal endoscopy. The diagnosis was confirmed on diagnostic laparoscopy and transabdominal preperitoneal repair of the defect was performed using prolene mesh. Her post-operative period was uneventful. Spigelian hernias are rare and patients can present with atypical symptoms as in this case. Thus, imaging plays a vital role in diagnosis. Management is surgical and has good outcomes. Keywords: case reports; rectus abdominis; ventral hernia.

Hyaluronic acid-British anti-Lewisite as a safer chelation therapy for the treatment of arthroplasty-related metallosis.

Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects-including peri-implant toxicity, aseptic loosening, and pseudotumor-as well as systemic toxic effects-including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo (t1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint.

Epidemiology, Trends, Utilization Disparities, and Outcomes of Catheter Ablation and Its Association With Coronary Vasospasm Amongst Patients With Non-valvular Atrial Fibrillation: A Nationwide Burden of Last Decade.

BACKGROUND: Catheter ablation (CA) is an important curative treatment for non-valvular atrial fibrillation (NVAF), however, nationwide data on its utilization and disparities is limited. Coronary vasospasm is a rare, life-threatening, peri-operative complication of CA with limited literature in Caucasians. METHODS: We performed a retrospective study on adult hospitalizations in the USA from 2007 to 2017 by obtaining the data from National Inpatient Sample. The primary endpoints of our study were to identify the utilization rate of CA, disparities in utilization, and study the outcomes associated with CA. The secondary endpoints of the study were to identify the incidence of coronary vasospasm amongst patients who underwent CA, evaluate their association, and identify the predictors of coronary vasospasm. RESULTS: From 35,906,946 patients with NVAF, 343641 (0.96%) underwent CA. Its utilization decreased from 1% in 2007 to 0.71% in 2017. Patients who underwent CA, compared to those without CA, fared better in terms of hospital length of stay, mortality rate, disability rate, and discharge to the non-home facility. Patients in the 50-75 years age group, Native Americans, those with private insurance, and median household income of 76-100th percentile were associated with higher odds of CA utilization. Urban teaching hospitals and large-bedded hospitals performed more ablations, while the Mid-West region fared lower than the South, the West, and the Northeast. The prevalence of coronary vasospasm was higher amongst CA in comparison without CA, however, in regression analysis, no significant association was demonstrated between CA and coronary vasospasm. CONCLUSION: CA is an important treatment modality that is associated with improved clinical outcomes. Identification of factors associated with lower utilization of CA and its disparities will help to mitigate the burden associated with NVAF.

Stromal Vascular Fraction for Osteoarthritis of the Knee Regenerative Engineering.

Purpose: The knee joint is prone to osteoarthritis (OA) due to its anatomical position, and several reports have implicated the imbalance between catabolic and anabolic processes within the joint as the main culprit, thus leading to investigations towards attenuation of these inflammatory signals for OA treatment. In this review, we have explored clinical evidence supporting the use of stromal vascular fraction (SVF), known for its anti-inflammatory characteristics for the treatment of OA. Methods: Searches were made on PubMed, PMC, and Google Scholar with the keywords "adipose fraction knee regeneration, and stromal vascular fraction knee regeneration, and limiting searches within 2017-2020. Results: Frequently found interventions include cultured adipose-derived stem cells (ADSCs), SVF, and the micronized/microfragmented adipose tissue-stromal vascular fraction (MAT-SVF). Clinical data reported that joints treated with SVF provided a better quality of life to patients. Currently, MAT-SVF obtained and administered at the point of care is approved by the Food and Drug Administration (FDA), but more studies including manufacturing validation, safety, and proof of pharmacological activity are needed for SVF. The mechanism of action of MAT-SVF is also not fully understood. However, the current hypothesis indicates a direct adherence and integration with the degenerative host tissue, and/or trophic effects resulting from the secretome of constituent cells. Conclusion: Our review of the literature on stromal vascular fraction and related therapy use has found evidence of efficacy in results. More research and clinical patient follow-up are needed to determine the proper place of these therapies in the treatment of osteoarthritis of the knee. Lay Summary: Reports have implicated the increased inflammatory proteins within the joints as the main cause of osteoarthritis (OA). This has attracted interest towards addressing these inflammatory proteins as a way of treatment for OA. The concentrated cell-packed portion of the adipose product stromal vascular fraction (SVF) from liposuction or other methods possesses anti-inflammatory effects and has been acclaimed to heal OA. Thus, we searched for clinical evidence supporting their use, for OA treatment through examining the literature. Data from various hospitals support that joints treated with SVF provided a better quality of life to patients. Currently, there is at least one version of these products that are obtained and given back to patients during a single clinic visit, approved by the FDA.

Primary Grynfeltt Lumbar Hernia: A Case Report.

A weakening or defect in posterolateral abdominal wall can lead to development of lumbar hernia. These defects are particularly common in Petit's inferior triangle or Grynfeltt-Lesshaft superior triangle. There are very few cases of primary lumbar hernias that have been described in literature till date. As it is a rare entity, it is often misdiagnosed, leading to delay in management. We present a case of a 66-year-old male with no previous surgery who presented with a mass in left lumbar region for last ten years. The mass gradually increased in size and caused vague dragging pain. On Computed tomography, the diagnosis of Grynfeltt hernia was made. The patient underwent a laparoscopic mesh repair and had an uneventful postoperative hospital stay. Although a rare entity, there should be a high degree of suspicion of a lumbar hernia when evaluating a case of a lumbar mass. Early diagnosis by computed tomography and management with open or minimally invasive techniques can prevent complications.

Injectable amnion hydrogel-mediated delivery of adipose-derived stem cells for osteoarthritis treatment.

Current treatment strategies for osteoarthritis (OA) predominantly address symptoms with limited disease-modifying potential. There is a growing interest in the use of adipose-derived stem cells (ADSCs) for OA treatment and developing biomimetic injectable hydrogels as cell delivery systems. Biomimetic injectable hydrogels can simulate the native tissue microenvironment by providing appropriate biological and chemical cues for tissue regeneration. A biomimetic injectable hydrogel using amnion membrane (AM) was developed which can self-assemble in situ and retain the stem cells at the target site. In the present study, we evaluated the efficacy of intraarticular injections of AM hydrogels with and without ADSCs in reducing inflammation and cartilage degeneration in a collagenase-induced OA rat model. A week after the induction of OA, rats were treated with control (phosphate-buffered saline), ADSCs, AM gel, and AM-ADSCs. Inflammation and cartilage regeneration was evaluated by joint swelling, analysis of serum by cytokine profiling and Raman spectroscopy, gross appearance, and histology. Both AM and ADSC possess antiinflammatory and chondroprotective properties to target the sites of inflammation in an osteoarthritic joint, thereby reducing the inflammation-mediated damage to the articular cartilage. The present study demonstrated the potential of AM hydrogel to foster cartilage tissue regeneration, a comparable regenerative effect of AM hydrogel and ADSCs, and the synergistic antiinflammatory and chondroprotective effects of AM and ADSC to regenerate cartilage tissue in a rat OA model.

The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering.

Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications.

Hyperactive MEK1 Signaling in Cortical GABAergic Neurons Promotes Embryonic Parvalbumin Neuron Loss and Defects in Behavioral Inhibition.

Many developmental syndromes have been linked to genetic mutations that cause abnormal ERK/MAPK activity; however, the neuropathological effects of hyperactive signaling are not fully understood. Here, we examined whether hyperactivation of MEK1 modifies the development of GABAergic cortical interneurons (CINs), a heterogeneous population of inhibitory neurons necessary for cortical function. We show that GABAergic-neuron specific MEK1 hyperactivation in vivo leads to increased cleaved caspase-3 labeling in a subpopulation of immature neurons in the embryonic subpallial mantle zone. Adult mutants displayed a significant loss of parvalbumin (PV), but not somatostatin, expressing CINs and a reduction in perisomatic inhibitory synapses on excitatory neurons. Surviving mutant PV-CINs maintained a typical fast-spiking phenotype but showed signs of decreased intrinsic excitability that coincided with an increased risk of seizure-like phenotypes. In contrast to other mouse models of PV-CIN loss, we discovered a robust increase in the accumulation of perineuronal nets, an extracellular structure thought to restrict plasticity. Indeed, we found that mutants exhibited a significant impairment in the acquisition of behavioral response inhibition capacity. Overall, our data suggest PV-CIN development is particularly sensitive to hyperactive MEK1 signaling, which may underlie certain neurological deficits frequently observed in ERK/MAPK-linked syndromes.

Recurrent Dermatofibrosarcoma Protuberance: A Case Report.

Dermatofibrosarcoma protuberance represents less than 0.1% of all tumors, treatment of which requires wide local excision (≥5cm) but recurrence is not rare. Here we present a 32-year male presented with a swelling of 15 x 6cm over the left lumbar region for which he underwent excision three years ago, the histopathological examination of the swelling, showed a malignant mesenchymal tumor and Immunohistochemistry features were suggestive of Dermatofibrosarcoma protuberance. After three years of interval, he again presented with complaints of swelling in the previously operated site for nine months and underwent excision of the mass with Split Thickness Skin Graft. Although the tumor was confined to the skin and subcutaneous tissue in the present case, the patient didn't undergo any adjuvant radiotherapy to avoid a possible relapse that would infiltrate deeper structures for the first time. Being a recurrent tumor, long-term follow-up is strongly recommended.

Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits.

The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a "tiger graft." The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix.

Systemic Therapy and Sequencing Options in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-analysis.

Importance: The treatment landscape for advanced hepatocellular carcinoma (HCC) has recently changed and become relatively confusing. Head-to-head comparisons between most of the available agents have not been performed and are less likely to be examined in a prospective fashion in the future. Therefore, a network meta-analysis (NMA) is helpful to compare different agents from across different trials. Objective: To evaluate comparative effectiveness of different systemic treatments in advanced patients with HCC across lines of therapy. Data Sources: We searched various databases for abstracts and full-text articles published from database inception through March 2020. Study Selection: We included phase 3 trials evaluating different vascular endothelial growth factor inhibitors (VEGFis), checkpoint inhibitors (CPIs), or their combinations in advanced HCC, in the first-line or refractory setting. Data Extraction and Synthesis: The reporting of this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The overall effect was pooled using the random effects model. Main Outcomes and Measures: Outcomes of interest included overall (OS) and progression-free survival (PFS). Findings: Fourteen trials (8 in the first-line setting and 6 in the second-line setting) at low risk of bias were included. The 8 trials in the first-line setting encompassed a total of 6290 patients, with an age range of 18 to 89 years. The 5 trials included in the second-line analysis encompassed a total of 2653 patients, with an age range of 18 to 91 years. Network meta-analysis showed the combination of atezolizumab and bevacizumab was superior in patients with HCC treated in the first-line setting compared with lenvatinib (HR, 0.63; 95% CI, 0.44-0.89), sorafenib (HR, 0.58; 95% CI, 0.42-0.80), and nivolumab (HR, 0.68; 95% CI, 0.48-0.98). In the refractory setting, NMA showed that all studied drugs had PFS benefit compared with placebo. However, this only translated into OS benefit with regorafenib (HR, 0.62; 95% CI, 0.51-0.75) and cabozantinib (HR, 0.76; 95% CI, 0.63-0.92) compared with placebo. In the NMA of patients with α-fetoprotein (AFP) levels of 400 ng/mL or greater, regorafenib, cabozantinib, and ramucirumab showed PFS and OS benefit compared with placebo with no superiority of an active drug compared with any others. Conclusions and Relevance: This systematic review and NMA of 14 trials found that atezolizumab and bevacizumab in combination is now considered the standard of care in the first-line setting in patients with advanced HCC. Regorafenib and cabozantinib are preferred options in refractory patients, with ramucirumab as an additional option in those with levels of AFP of 400 ng/mL or higher. Future trials should focus on other potential combinations and best treatment strategy in patients with prior VEGFi/CPI exposure.

Emergence of the Stem Cell Secretome in Regenerative Engineering.

The secretome is defined as the set of molecules and biological factors that are secreted by cells into the extracellular space. In the past decade, secretome-based therapies have emerged as a promising approach to overcome the limitations associated with cell-based therapies for tissue and organ regeneration. Considering the growing number of recent publications related to secretome-based therapies, this review takes a step-by-step engineering approach to evaluate the role of the stem cell secretome in regenerative engineering. We discuss the functional benefits of the secretome, the techniques used to engineer the secretome and tailor its therapeutic effects, and the delivery systems and strategies that have been developed to use the secretome for tissue regeneration.