Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway.

OBJECTIVES: This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival. METHODS: The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry. RESULTS: LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1ß signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells. CONCLUSION: LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival.

The rare complication of vascular malformations of the limb after sclerotherapy: a report of 3 cases and brief literature review.

BACKGROUND: Vascular malformations are common but complicated types of disease in infants, with unclear causes and lack of effective prevention. The symptoms usually do not disappear and tend to progress without medical intervention. It is extremely necessary to choose correct treatment options for different types of vascular malformations. A large number of studies have confirmed that sclerotherapy has a tendency to become the first-line treatment in near future, but it is also associated with mild or severe complications. Furthermore, to our knowledge, the serious adverse event of progressive limb necrosis has not been systematically analyzed and reported in the literature. CASE PRESENTATION: Three cases (two females and one male) were presented who were all diagnosed as vascular malformations and were treated by several sessions of interventional sclerotherapy. Their previous medical records showed the use of several sclerosants in different sessions including Polidocanol and Bleomycin. The sign of limb necrosis did not occur during the first sclerotherapy, but after the second and third sessions. Furthermore, the short-term symptomatic treatment could improve the necrosis syndrome, but could not change the outcome of amputation. CONCLUSION: Sclerotherapy undoubtedly tends to be the first-line treatment in near future, but the adverse reactions still remain major challenges. Awareness of progressive limb necrosis after sclerotherapy and timely management by experts in centers of experience of this complication can avoid amputation.

The free chimeric medial sural artery perforator flap for individualised and three-dimensional reconstruction of complex soft-tissue defects in extremities.

Trauma or lesion resection often causes complex wounds with deep soft tissue defects in extremities. Simply covering with a skin flap will leave a deep dead space resulting in infection, non-healing wounds, and poor long-term outcomes. Thus, effectively reconstructing complex wounds with dead space leaves a clinical challenge. This manuscript presents our experience using chimeric medial sural artery perforator (cMSAP) flap, to reconstruct complex soft tissue defects of the extremities, thereby exploring broader analysis and indications for future reference. Between March 2016 and May 11, 2022, patients (8 males and 3 females) with a mean age of 41 years (range from 26 to 55 years) underwent reconstructive surgery with the cMSAP flap. The cMSAP flap consists of an MSAP skin paddle and a medial sural muscle paddle. The size of the MSAP skin paddle ranged between 9 × 5 cm and 20 × 6 cm, and the size of the medial sural muscle paddle ranged between 2 × 2 cm and 14 × 4 cm. Primary closure of the donor site was achieved in all cases. Of the 11 patients, the cMSAP flap survived in 10 cases. The vascular compromise occurred in one special case and was treated with surgical procedures. The mean follow-up duration was 16.5 months (range of 5-25 months). Most patients present satisfactory cosmetic and functional results. The free cMSAP flap is a good option for reconstructing complex soft tissue defects with deep dead space in extremities. The skin flap can cover the skin defect, and the muscle flap can fill the dead space against infection. In addition, three types of cMSAP flaps can be used in a broader range of complex wounds. This procedure can achieve an individualised and three-dimensional reconstruction of the defects and minimise the donor site morbidities.

Surgery-associated acquired hemophilia A: a report of 2 cases and review of literature.

BACKGROUND: Acquired Hemophilia A (AHA) is a rare bleeding diathesis in patients with no previous personal or family bleeding history. The diagnosis of this disease often delays due to unfamiliarity of physicians with it, which leads to its high mortality rate. CASE PRESENTATION: Two cases (one 12 years old female and another 18 years old male) were admitted for right upper abdominal mass and right upper abdominal pain respectively at different times. Pre-operative diagnosis of both cases was congenital choledochal cyst. They suffered continuous gastrointestinal bleeding (hematemesis and melena) with reduced hemoglobin to 54 g/L and 60 g/L after Roux-en-Y anastomosis respectively. To investigate the exact bleeding site, Digital subtraction angiography (DSA) of case 1 showed contrast overflow at small branch of proper hepatic artery but had unremarkable result for case 2, whereas gastroscopy of both cases showed unremarkable results. Multiple surgeries were also performed for hemostatic purpose but each time no active bleeding site was found. Finally, hematologists consultation was mandated in both cases and they were diagnosed as acquired haemophilia A. However, unfortunately case 1 patient could not survive because of sever hemorrhage and infection while Case 2 of 18 years old male survived after proper haemophilia treatment catalog. CONCLUSION: Awareness about surgery associated acquired haemophilia A (SAHA) can facilitate quick diagnosis and lifesaving management because the mortality rate in SAHA is high due to lake of knowledge or late recognition of the disease. Bleeding always occurs at surgical sites and it can occur immediately within few hours after surgery in some cases. Hemorrhage may be severe or even life threatening and it presents a special challenge for diagnosis and treatment in a patient who has just undergone a surgical procedure. The treatment strategies for AHA include resumption of hemostasis with either recombinant porcine factor VIII (rpFVIII) or bypassing agents and immunosuppressive therapy to suppress the production of the factor VIII inhibitor.

Successful management of a rare radius schwannoma mimicking malignant bone tumors: A case report and literature review.

Background: Schwannomas are benign tumors originating from Schwann cells, frequently occurring in the spinal cord and peripheral nerves. Intraosseous schwannomas, a rare subset, account for approximately 0.2% of schwannomas. Intraosseous schwannomas commonly impinge the mandible, followed by the sacrum and the spine. By far, only three cases of radius intraosseous schwannomas have been reported in PubMed. The tumor was treated differently in all three cases, resulting in different outcomes. Case presentation: A 29-year-old male construction engineer who complained of a painless mass on the radial aspect of the right forearm was diagnosed with an intraosseous schwannoma of the radius based on radiography, three-dimensional computed tomography reconstruction, magnetic resonance imaging, pathological examination, and immunohistochemistry. A different surgical approach was employed to reconstruct the radial graft defect using bone microrepair techniques, resulting in more reliable bone healing and early functional recovery. Meanwhile, no clinical and radiographic findings suggestive of recurrence were observed at the 12-month follow-up. Conclusion: Vascularized bone flap transplantation combined with three-dimensional imaging reconstruction planning might yield better results for repairing small segmental bone defects of the radius caused by intraosseous schwannomas.

Improving the ischemia-reperfusion injury in vascularized composite allotransplantation: Clinical experience and experimental implications.

Long-time ischemia worsening transplant outcomes in vascularized composite allotransplantation (VCA) is often neglected. Ischemia-reperfusion injury (IRI) is an inevitable event that follows reperfusion after a period of cold static storage. The pathophysiological mechanism activates local inflammation, which is a barrier to allograft long-term immune tolerance. The previous publications have not clearly described the relationship between the tissue damage and ischemia time, nor the rejection grade. In this review, we found that the rejection episodes and rejection grade are usually related to the ischemia time, both in clinical and experimental aspects. Moreover, we summarized the potential therapeutic measures to mitigate the ischemia-reperfusion injury. Compare to static preservation, machine perfusion is a promising method that can keep VCA tissue viability and extend preservation time, which is especially beneficial for the expansion of the donor pool and better MHC-matching.

Minimally invasive left internal mammary artery harvesting techniques during the learning curve are safe and achieve similar results as conventional LIMA harvesting techniques.

BACKGROUND: Internal thoracic arteries (ITAs) are considered to be the standard conduits used for coronary revascularization. Recently minimally invasive procedures are performed to harvest ITAs. The aim of this retrospective cohort study is to observe the effect and safety of less invasive LIMA harvesting approaches in the learning curve compared to conventional harvesting. METHODS: We retrospectively analyzed the data of 138 patients divided into three different groups based on the LIMA harvesting techniques: conventional sternotomy LIMA harvesting, CSLH (n: 64), minimally invasive direct LIMA harvesting, MIDLH (n: 42), and robotic-assisted LIMA harvesting, RALH (n: 32). The same 138 patients were also divided into sternotomy (n: 64), and non-sternotomy (n: 74) groups keeping both MIDLH and RALH in the non-sternotomy category. Parameters associated with LIMA's quality and some other perioperative parameters such as harvesting time, LIMA damage, perioperative myocardial infarction, ventilation time, 24 h drainage, ICU stay, hospital mortality, computed tomographic angiography (CTA) LIMA patency on discharge, and after one year were recorded. RESULTS: The mean LIMA harvesting time was 36.9 ± 14.3, 74.4 ± 24.2, and 164.7 ± 51.9 min for CSLH, MIDLH, and RALH groups respectively (p < 0.001). One patient 1/32 (3.1%) in the RALH group had LIMA damage while the other two groups had none. One-month LIMA CTA patency was 56/57 (98.2%), 34/36 (94.4%), and 27/27 (100%) (p = 0.339), while 1 year CTA patency was 47/51 (92.1%), 30/33 (90.9%), and 24/25 (96%) for CSLH, MIDLH, and RALH groups respectively (p = 0.754). In the case of sternotomy vs non-sternotomy, the LIMA harvesting time was 36.9 ± 14.3 and 113.6 ± 59.3 min (p < 0.001). CTA patency on discharge was 56/57 (98.2%) and 61/63 (96.8%) (p = 0.619), while 1 year CTA patency was 47/51 (92.1%) and 54/58 (93.1%) (p = 0.850) for sternotomy vs non-sternotomy groups. CONCLUSION: Minimally invasive left internal mammary artery harvesting techniques during the learning curve are safe and have no negative impact on the quality of LIMA. Perioperative outcomes are comparable to conventional procedures except for prolonged harvesting time. RALH is the least invasive and most time-consuming procedure during the learning curve. These procedures are safe and can be performed for selected patients even during the learning curve.

Effect of bilateral internal thoracic artery harvesting on deep sternal wound infection in diabetic patients: Review of literature.

Instead of its documented superiority of patency and long-term outcomes, the bilateral internal thoracic artery grafts are underused in the general population, and its use is controversial and debatable in diabetic patients due to long surgery duration, post-surgical bleeding, and sternal wound complications such as sternal wound infection, mediastinitis, and sternal wound dehiscence. This review article is particularly focused on deep sternal wound infection (DSWI) of bilateral internal thoracic artery (BITA) grafts in diabetic patients with comparison to single internal thoracic artery (SITA) graft.

Solitary extramedullary plasmacytoma presenting as an adrenal tumor: case report and literature review.

Solitary extramedullary plasmacytoma, an extremely rare case which accounts for about 3% of all plasma cell neoplasms, often occurs in the head and neck region such as para nasal sinuses, nasal cavity and oral cavity, it also occurs in the lymph nodes, lungs, thyroid, intestine, liver, pancreas, testis, breast, or skin. Isolated primary plasmacytoma of adrenal is extremely rare and only nine documented cases have been reported in the literature. We are presenting the 10th case which is the youngest patient until now with symptoms of fever and hepatosplenomegaly. A 19-year-old female was admitted with an irregular fever for 20 days. After a series of investigations were carried out there were no CRAB symptoms (hypercalcemia, renal failure, anemia and bone lesions), no free light chain and no more than 10% increase in plasma cell on bone marrow examination. Computed tomography (CT) scan revealed a tumor in the left adrenal region, and it was diagnosed to be a solitary extramedullary plasmacytoma on biopsy. She underwent the tumor resection one month after admission and recovered well after operation without fever and was discharged from hospital on the thirteenth post-operative day. She has been followed up for 5 years without any sign and symptom of tumor recurrence. Extramedullary plasmacytoma of adrenal gland in an extremely rare disease and usually diagnosed late in life but it can present in younger patients with variable symptoms. However, the surgical treatment yields excellent long-term results. So, complete surgical resection of the lesion is not only a good diagnostic measure, but also an intent-for-cure treatment for solitary adrenal extramedullary plasmacytoma.