Necrotizing Fasciitis of the Thigh as Unusual Colonoscopic Polypectomy Complication: Review of the Literature with Case Presentation

Necrotizing fasciitis (NF) is an infection characterized by necrosis of the superficial muscle fascia and surrounding soft tissues. It usually occurs following skin breaches from penetrating traumas or high-degree burns. Less frequently, it could be related to major abdominal surgery. However, no cases of thigh NF after minor abdominal procedures have ever been reported. A previously healthy 59-year-old male patient underwent a colonoscopic polypectomy. After the procedure, the patient developed an increasing right groin pain. The CT scan showed a gas collection in the right retroperitoneum space and in the right thigh soft tissues. Thus, a right colon perforation was hypothesized, and the patient was moved to the nearest surgery department and underwent a right hemicolectomy procedure. During surgery, the right thigh was also incised and drained, with gas and pus leakage. Nevertheless, the right lower limb continued to swell, and signs of systemic infection appeared. Afterward, clinical conditions continued to worsen despite the drainage of the thigh and antibiotic therapy, and the patient died of septic shock after just two days. This case shows that, although rare, lower limb NF should be considered among the causes of early post-operative local painful symptoms.

Genome-Wide CRISPR/Cas9-Based Screening for Deubiquitinase Subfamily Identifies Ubiquitin-Specific Protease 11 as a Novel Regulator of Osteogenic Differentiation

The osteoblast differentiation capacity of mesenchymal stem cells must be tightly regulated, as inadequate bone mineralization can lead to osteoporosis, and excess bone formation can cause the heterotopic ossification of soft tissues. The balanced protein level of Msh homeobox 1 (MSX1) is critical during normal osteogenesis. To understand the factors that prevent MSX1 protein degradation, the identification of deubiquitinating enzymes (DUBs) for MSX1 is essential. In this study, we performed loss-of-function-based screening for DUBs regulating MSX1 protein levels using the CRISPR/Cas9 system. We identified ubiquitin-specific protease 11 (USP11) as a protein regulator of MSX1 and further demonstrated that USP11 interacts and prevents MSX1 protein degradation by its deubiquitinating activity. Overexpression of USP11 enhanced the expression of several osteogenic transcriptional factors in human mesenchymal stem cells (hMSCs). Additionally, differentiation studies revealed reduced calcification and alkaline phosphatase activity in USP11-depleted cells, while overexpression of USP11 enhanced the differentiation potential of hMSCs. These results indicate the novel role of USP11 during osteogenic differentiation and suggest USP11 as a potential target for bone regeneration.

Metastatic Progression of Osteosarcomas: A Review of Current Knowledge of Environmental versus Oncogenic Drivers

Metastases of osteosarcomas are heterogeneous. They may grow simultaneously with the primary tumor, during treatment or shortly after, or a long time after the end of the treatment. They occur mainly in lungs but also in bone and various soft tissues. They can have the same histology as the primary tumor or show a shift towards a different differentiation path. However, the metastatic capacities of osteosarcoma cells can be predicted by gene and microRNA signatures. Despite the identification of numerous metastasis-promoting/predicting factors, there is no efficient therapeutic strategy to reduce the number of patients developing a metastatic disease or to cure these metastatic patients, except surgery. Indeed, these patients are generally resistant to the classical chemo- and to immuno-therapy. Hence, the knowledge of specific mechanisms should be extended to reveal novel therapeutic approaches. Recent studies that used DNA and RNA sequencing technologies highlighted complex relations between primary and secondary tumors. The reported results also supported a hierarchical organization of the tumor cell clones, suggesting that cancer stem cells are involved. Because of their chemoresistance, their plasticity, and their ability to modulate the immune environment, the osteosarcoma stem cells could be important players in the metastatic process.

Quantitative Assessment of 3D Printed Blood Vessels Produced with J750™ Digital Anatomy™ for Suture Simulation

Blood vessels anastomosis is one of the most challenging and delicate tasks to learn in many surgical specialties, especially for vascular and abdominal surgeons. Such a critical skill implies a learning curve that goes beyond technical execution. The surgeon needs to gain proficiency in adapting gestures and the amount of force expressed according to the type of tissue he/she is dealing with. In this context, surgical simulation is gaining a pivotal role in the training of surgeons, but currently available simulators can provide only standard or simplified anatomies, without the chance of presenting specific pathological conditions and rare cases. 3D printing technology, allowing the manufacturing of extremely complex geometries, find a perfect application in the production of realistic replica of patient-specific anatomies. According to available technologies and materials, morphological aspects can be easily handled, while the reproduction of tissues mechanical properties still poses major problems, especially when dealing with soft tissues. The present work focuses on blood vessels, with the aim of identifying – by means of both qualitative and quantitative tests – materials combinations able to best mimic the behavior of the biological tissue during anastomoses, by means of J750™ Digital Anatomy™ technology and commercial photopolymers from Stratasys. Puncture tests and stitch traction tests are used to quantify the performance of the various formulations. Surgical simulations involving anastomoses are performed on selected clinical cases by surgeons to validate the results. A total of 37 experimental materials were tested and 2 formulations were identified as the most promising solutions to be used for anastomoses simulation. Clinical applicative tests, specifically selected to challenge the new materials, raised additional issues on the performance of the materials to be considered for future developments.

Seropositivity for CMV, EBV, HBV, HCV, and HIV in Leukemia Patients and Its Relationship with Cytogenetic Changes

Introduction: Leukemias are involving the bone marrow and the soft tissues in inner parts of the bones, where new blood cells are formed. This malignancy is the most common pediatric cancer, which its etiologic causes are not well understood. This multifactorial disease is believed to linked with genetic and non-hereditary environmental factors. Cytogenic analyses of chromosomal abnormalities provide diagnostic and prognostic values in leukemia patients. Given the high prevalence of viral diseases and clinical suspicions on the relationship between certain viral infections and leukemia, it is necessary to investigate this possible relationship, especially in third-world countries. The present study recruited 65 children with leukemia (AML, CML, or ALL) who were presented to two tertiary hospitals. At first, all the patients underwent testing for HBV, HCV, CMV, EBV, and HIV. Bone marrow specimens were studied for identifying possible chromosomal abnormalities in cytogenic investigations. According to our findings, there was a relationship between incidence of leukemia, the 12:21 chromosomal translocation and CMV infection. Therefore, preventing CMV infection can lead to a reduced incidence of leukemia. It is expected that the findings of this study enlighten the scientists to conduct more extensive research on the relationship between viral diseases and leukemia in third-world countries.Method:The present study recruited 65 children with leukemia (AML, CML, or ALL) who were presented to two tertiary hospitals. At first, all the patients underwent testing forHBV, HCV, CMV, EBV, and HIV. Bone marrow specimens were studied for identifying possible chromosomal abnormalities in cytogenic investigations.Result:According to our findings,there was a relationship between the incidence of leukemia,the 12:21 chromosomal translocation, and CMV infection.Therefore, preventing CMV infection can lead to a reducedincidence of leukemia.Conclusion:In this study, we demonstrated that leukemia is relevant to the 12:21 chromosomal translocation and CMV virus infections, So the reduction in leukemia prevalence is dependent on the prevention of CMV disease. It is expected that the findings ofthis studyenlighten the scientists to conduct more extensive researchon the relationship between viral diseasesand leukemia in third-world countries.Trial registrations:Clinical trial registration code:IR.AJAUMS.REC.1399.161Evaluated by: AJA UNIVERSITY OF MEDICAL SCIENCESApproval Date:2020-11-15Approval statement: The project was found to be in accordance with the ethical principles and the national norms and standards for conducting Medical Research in Iran.

Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort

Purpose: We aimed to report the clinical and immunological characteristics of variant type X91+ CGD in a Chinese cohort.Methods: The clinical manifestations and immunological phenotypes of X91+ CGD patients were collected. Dihydrorhodamine (DHR) analysis was performed to evaluate neutrophil function. Gp91phox protein expression was determined by flow cytometry-based extracellular staining with the monoclonal antibody (mAb) 7D5. Results: X91+CGD patients accounted for 8% (7/85) of all patients with GCD. The median onset age in the 7 X91+ CGD patients was 4 months. Six patients received the same BCG vaccine strain, and three had probable BCG infections. Moreover, 4 patients were highly suspected of having Mycobacterium tuberculosis infection. Recurrent infections of the lungs and soft tissues (3/7) were the most common symptoms. Two patients had noninfectious recurrent oral ulcers and received interferon gamma (IFN-γ) treatment afterward. In our cohort, the stimulation index (SI) of the 7 X91+ CGD patients ranged widely from 1.9 to 67.5, while the SI ranged from 1.2 to 35.7 in patents with X910 CGD. The level of SI between these two groups was statistically significant (P<0.05). CYBB mutations associated with X91+CGD were usually located in or near the FAD and NADPH binding domains. Three new X91+ CGD related mutations (c.1462-2 A>T, c.1243C>T and c.925G>A) were identified. Conclusions: Variant type X91+ CGD may have varied severities of clinical manifestations. Moreover, the laboratory findings of X91+ CGD could present with a moderate neutrophil stimulation index. We should deepen our understanding of the X91+ variant CGD to prevent missed diagnosis.

3β,23-Dihydroxy-12-ene-28-ursolic Acid Isolated from Cyclocarya paliurus Alleviates NLRP3 Inflammasome-Mediated Gout via PI3K-AKT-mTOR-Dependent Autophagy

Gout is regarded as a painful inflammatory arthritis induced by the deposition of monosodium urate crystals in joints and soft tissues. Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-mediated IL-1β production plays a crucial role in the pathological process of gout. Cyclocarya paliurus (CP) tea was found to have an effect on reducing the blood uric acid level of people with hyperuricemia and gout. However, its medicinal ingredients and mechanism for the treatment of gout are still unclear. Thus, this study was designed to investigate the effects of the active triterpenoids isolated from C. paliurus on gout and explore the underlying mechanism. The results showed that compound 2 (3β,23-dihydroxy-12-ene-28-ursolic acid) from C. paliurus significantly decreased the protein expression of IL-1β, caspase-1, pro-IL-1β, pro-caspase-1, and NLRP3. Furthermore, the production of ROS in the intracellular was reduced after compound 2 treatment. However, ROS agonist rotenone remarkably reversed the inhibitory effect of compound 2 on the protein expression of NLRP3 inflammasome. Additionally, the expression level of LC3 and the ratio of LC3II/LC3I were increased, but the expression level of p62 was suppressed by compound 2 whereas an autophagy inhibitor 3-methyladenine (3-MA) significantly abolished the inhibitory effects of compound 2 on the generation of ROS and the protein expression of NLRP3 inflammasome. Moreover, compound 2 could ameliorate the expression ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Interestingly, mTOR activator MHY-1485 could block the promotion effect of compound 2 on autophagy regulation and inhibitory effect of compound 2 on induction of ROS and IL-1β. In conclusion, these findings suggested that compound 2 may effectively improve NLRP3 inflammasome-mediated gout via PI3K-AKT-mTOR-dependent autophagy and could be further investigated as a potential agent against gout.

A Review on Damage and Rupture Modelling for Soft Tissues

Computational modelling of damage and rupture of non-connective and connective soft tissues due to pathological and supra-physiological mechanisms is vital in the fundamental understanding of failures. Recent advancements in soft tissue damage models play an essential role in developing artificial tissues, medical devices/implants, and surgical intervention practices. The current article reviews the recently developed damage models and rupture models that considered the microstructure of the tissues. Earlier review works presented damage and rupture separately, wherein this work reviews both damage and rupture in soft tissues. Wherein the present article provides a detailed review of various models on the damage evolution and tear in soft tissues focusing on key conceptual ideas, advantages, limitations, and challenges. Some key challenges of damage and rupture models are outlined in the article, which helps extend the present damage and rupture models to various soft tissues.