Optimizing mesenchymal stem cell extracellular vesicles for chronic wound healing: Bioengineering, standardization, and safety.

Chronic wounds represent a significant global burden, afflicting millions with debilitating complications. Despite standard care, impaired healing persists due to factors like persistent inflammation and impaired tissue regeneration. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer an innovative regenerative medicine approach, delivering stem cell-derived therapeutic cargo in engineered nanoscale delivery systems. This review examines pioneering bioengineering strategies to engineer MSC-EVs into precision nanotherapeutics for chronic wounds. Emerging technologies like CRISPR gene editing, microfluidic manufacturing, and biomimetic delivery systems are highlighted for their potential to enhance MSC-EV targeting, optimize therapeutic cargo enrichment, and ensure consistent clinical-grade production. However, key hurdles remain, including batch variability, rigorous safety assessment for potential tumorigenicity, immunogenicity, and biodistribution profiling. Crucially, collaborative frameworks harmonizing regulatory science with bioengineering and patient advocacy hold the key to expediting global clinical translation. By overcoming these challenges, engineered MSC-EVs could catalyze a new era of off-the-shelf regenerative therapies, restoring hope and healing for millions afflicted by non-healing wounds.

Analysis of reconstructed oropharynx shape after total glossolaryngectomy reconstruction using a free rectus abdominis musculocutaneous flap.

Introduction: Restoring oral intake through oropharyngeal reconstruction is vital for patients undergoing total glossolaryngectomy. Despite its importance, research in this area is limited, leaving clinicians with few guidelines. The debate regarding the optimal shape of the reconstructed oropharynx highlights the need for further research. Methods: This retrospective study analysed data from 16 consecutive patients who underwent primary reconstruction with a free rectus abdominis musculocutaneous flap after total glossolaryngectomy at the University of the Ryukyus Hospital between April 2015 and March 2022. Parameters assessed included reconstructed oropharynx shape (flat or funnel-shaped), demographics, flap characteristics, post-operative course and oral intake outcomes. Results: Among the 16 patients, 10 had flat oropharynx, whereas 6 had a funnel-shaped oropharynx. At 6 months post-surgery, 13 patients resumed oral feeding, whereas 3 did not. Significant differences were observed between the groups in preoperative body mass index (21.1 kg/m² vs 17.8 kg/m², Welch's t-test, p=0.035) and days until the first oral intake (34.2 days vs 19.2 days, Welch's t-test, p=0.01). However, no significant differences were found in the form of oral intake at 6 months after surgery (Fisher's exact test, p=0.518). Conclusion: This study suggests that the shape of the reconstructed oropharynx (flat or funnel-shaped) does not significantly impact long-term post-operative oral intake. These findings provide valuable insights into oropharyngeal reconstruction outcomes after total glossolaryngectomy and offer guidance for future research in this area. Nevertheless, further studies are warranted to elucidate the clinical implications of these findings and address any limitations of this study, particularly those regarding sample size constraints.

Autologous Rib Cartilage Reconstruction After Silicone Implant Removal in a Patient With Bilateral Cleft Lip and Palate: A Case Report.

Cleft lip rhinoplasty (CLR) corrects nasal deformities in cleft lip and palate patients. However, limitations exist in some countries like Japan regarding the use of silicone implants for CLR. While historical reports mention their use since the 1980s, long-term data is lacking. This case report describes a 53-year-old Japanese woman with bilateral cleft lip and palate who received a CLR with a silicone implant over 30 years ago. The implant calcified, causing nasal dorsum skin hardening and thinning, raising concerns of extrusion. To prevent potential extrusion, the implant was removed and replaced with autologous seventh rib cartilage grafts. Various grafting techniques were used for basal support, dorsal augmentation, and nasal tip refinement. The postoperative evaluation showed excellent results with no complications. This case highlights the importance of long-term follow-up after CLR with silicone implants and advocates for autologous rib cartilage as a reliable alternative. Reporting such cases is crucial for informing patient management and research on the long-term safety of silicone implants in CLR.

Sternocleidomastoid Muscle Flap in an Older Patient With Congenital Muscular Torticollis.

Congenital muscular torticollis (CMT) is caused by muscle damage during childbirth, tumors, or masses within the muscles and generally resolves with physical therapy during infancy. In this study, we performed reconstruction after resection of a parotid gland tumor using a sternocleidomastoid muscle (SCMM) flap in an older patient with neglected CMT. The patient was a 64-year-old woman who had had a left-sided oblique neck since infancy but had never received any treatment, including physical therapy. She underwent parotid tumor resection and SCMM flap transfer. The SCMM flap can be safely elevated using indocyanine green fluorescence angiography, with the middle pedicle serving as the feeding vessel to fill the parotid defect. Three months after surgery, the torticollis had improved and the cheek depression was not noticeable, indicating the effectiveness of surgical treatment for CMT in older patients and the possibility of using SCMM as a muscle flap.

Management of Axillary Contracture in Poland Syndrome: Differentiating Fibrous Band and Skin for Optimal Release.

Poland syndrome (PS), an uncommon congenital unilateral aplasia of chest wall muscles, may exhibit rare accompanying signs, such as axillary webbing or contractures. The existing literature on the specific management of axillary contractures is limited. In this report, we present the case of a 10-year-old girl with PS manifesting an axillary web containing a fibrous band, which was successfully surgically corrected by a double-opposing Z-plasty. Our surgical approach entailed a meticulous distinction between the deep fibrous band and the superficial cutaneous layer, guided by histopathological findings that indicated the presence of tendon-like tissue, ultimately yielding excellent outcomes. This report will help expand knowledge by highlighting the unique manifestation of PS and emphasizing the importance of employing appropriate treatment approaches. Moreover, addressing both tendon and skin components is essential for optimal contracture release in PS.

Management of Rheumatoid Arthritis: Possibilities and Challenges of Mesenchymal Stromal/Stem Cell-Based Therapies.

Rheumatoid arthritis (RA) is a highly prevalent, chronic, and progressive autoimmune disorder primarily affecting joints and muscles. The associated inflammation, pain, and motor restriction negatively impact patient quality of life (QOL) and can even contribute to premature mortality. Further, conventional treatments such as antiinflammatory drugs are only symptomatic. Substantial progress has been made on elucidating the etiopathology of overt RA, in particular the contributions of innate and adaptive immune system dysfunction to chronic inflammation. Although the precise mechanisms underlying onset and progression remain elusive, the discovery of new drug targets, early diagnosis, and new targeted treatments have greatly improved the prognosis and QOL of patients with RA. However, a sizable proportion of patients develop severe adverse effects, exhibit poor responses, or cannot tolerate long-term use of these drugs, necessitating more effective and safer therapeutic alternatives. Mounting preclinical and clinical evidence suggests that the transplantation of multipotent adult stem cells such as mesenchymal stromal/stem cells is a safe and effective treatment strategy for controlling chronic inflammation and promoting tissue regeneration in patients with intractable diseases, including RA. This review describes the current status of MSC-based therapies for RA as well as the opportunities and challenges to broader clinical application.

Peritonsillar abscess subsequently complicated by Ludwig's angina.

The images of this article are clinical pictures of peritonsillar abscess subsequently complicated by Ludwig's angina of a 68-year-old man.

Screening and ecological risk of 1200 organic micropollutants in Yangtze Estuary water.

The Yangtze River, the third largest river in the world, has been polluted by various organic chemicals. In 2018, China decided to implement ecological restoration of the Yangtze River to protect the river. However, except for some conventional pollution indices such as COD (Chemical Oxygen Demand) and NH4+-N, the overall levels and risks of a wide variety of organic micropollutants (OMPs) in the Yangtze Estuary is not clear. Herein, results from a wide-range screening on levels and risks of OMPs in the Yangtze Estuary water were reported. 36 water samples were collected at 9 sites in the Yangtze Estuary in 2012 and 2013. Approximately 1200 OMPs were screened. A total of 131 OMPs were detected with total concentrations ranging from 1.8×103 to 9.7×103 ng/L. A tiered strategy was proposed to simplify the assessment of multi-substance ecological risks. Results showed that risk quotient (RQ) for 77% of the OMPs was less than 0.1. For 20 OMPs with RQ ≥ 0.1, joint probabilistic risks were assessed by species sensitivity distribution models. The joint risks as expressed by multi-substance potentially affected fractions are > 5%, and are not insignificant. The results may serve as a benchmark for protecting biodiversity in the Yangtze Estuary, as China motivated to have a fundamental improvement on the environmental quality by 2035.

Method to prevent cheek depression using an island sternocleidomastoid muscle flap with the middle pedicle as a feeding vessel in immediate reconstruction of the facial nerve with the sural nerve following resection of a parotid gland tumor.

Many surgeons have demonstrated the validity of sternocleidomastoid muscle flaps for the reconstruction of head and neck tumors. We present a case in which we used an island sternocleidomastoid muscle flap to reconstruct a cheek depression after excision of a malignant parotid tumor. A 44-year-old woman presented with a right malignant parotid tumor. We performed total resection of the parotid gland and facial nerve with the sural nerve and reconstructed the facial nerve and cheek depression with an island sternocleidomastoid muscle flap. The sternal head of the right sternocleidomastoid muscle was cut at the cranial and caudal segments to elevate it as an island flap. We used the superior thyroid artery as the sole pedicle for the island muscle flap. At 1 year and 3 months after the operation, the mimic muscles had gradually recovered and progressed without complications such as Frey syndrome, cervical motor dysfunction, or concave deformation of the neck and cheeks.

The Internal Oblique Muscle Flap with Synthetic Mesh Reinforcement for a Large, Contaminated Abdominal Wall Defect.

We report a case of a large mediocaudal abdominal defect in contaminated circumstances with no residual rectus abdominis muscle that was reconstructed using an internal oblique muscle flap with large-pore polypropylene mesh reinforcement. The internal oblique muscle flap can reconstruct the lower abdominal midline without leaving any additional conspicuous scar. Previous studies showed that large-pore polypropylene mesh in contaminated wounds has a minimal difference in terms of infection rate, and less frequent occurrence of hernia, compared even with biological meshes. We believe that this method could be a strong and cosmetically satisfying option for large mediocaudal abdominal wall reconstruction.

A case of fulminant type 1 diabetes masquerading acute pancreatitis.

Fulminant type 1 diabetes is a novel and life-threatening subtype of type 1 diabetes characterized by its markedly abrupt onset and hyperglycemia with a relatively low glycated hemoglobin level at the onset. We herein describe a typical case of fulminant type 1 diabetes who presented with abdominal pain and vomiting, and whose laboratory test revealed elevated pancreatic enzymes. He was initially diagnosed with acute pancreatitis, but occult and prolonged hyperglycemia eventually led to a diagnosis of fulminant type 1 diabetes.