Local and Systemic Peptide Therapies for Soft Tissue Regeneration: A Narrative Review.

Background: The musculoskeletal system, due to inherent structure and function, lends itself to contributing toward joint pain, whether from inflammatory disorders such as rheumatoid arthritis, degenerative diseases such as osteoarthritis, or trauma causing soft tissue injury. Administration of peptides for treatment of joint pain or inflammation is an emerging line of therapy that seeks to offer therapeutic benefits while remaining safe and relatively non-invasive. Purpose: The purpose of this study is to review the current literature on existing oral peptide agents, intra-articular peptide agents, and new developments in human trials to assess route of administration (RoA) for drug delivery in terms of soft tissue regeneration. Study Design: Narrative Review. Methods: A comprehensive literature search was conducted using the PubMed database. The search included medical subject headings (MeSH) terms related to peptide therapy, soft tissue regeneration, and RoA. Inclusion criteria comprised articles focusing on the mechanisms of action of peptides, clinical or biochemical outcomes, and review articles. Exclusion criteria included insufficient literature or studies not meeting the set evidence level. Conclusion: The review identified various peptides demonstrating efficacy in soft tissue repair. Oral and intra-articular peptides showed distinct advantages in soft tissue regeneration, with intra-articular routes providing localized effects and oral routes offering systemic benefits. However, both routes have limitations in bioavailability and absorption. Still in their infancy, further inquiries/research into the properties and efficacy of emerging peptides will be necessary before widespread use. As a viable alternative prior to surgical intervention, peptide treatments present as promising candidates for positive outcomes in soft tissue regeneration.

Carbidopa, an activator of aryl hydrocarbon receptor, suppresses IDO1 expression in pancreatic cancer and decreases tumor growth.

IDO1 is an immunomodulatory enzyme responsible for tryptophan catabolism. Its expression in immune cells, especially the DCs, has attracted attention because it leads to tryptophan depletion at the immunological synapse, thereby causing T-cell anergy and immune evasion by the tumor cells. Cancer cells also overexpress IDO1. Immunotherapy targeting IDO1 has been one of the focus areas in cancer biology, but lately studies have identified non-immune related functions of IDO1 leading to a paradigm shift with regard to IDO1 function in the context of tumor cells. In this study, we show that PDAC tissues and PDAC cells overexpress IDO1. The expression level is reciprocally related to overall patient survival. We further show that carbidopa, an FDA-approved drug for Parkinson's disease as well as an AhR agonist, inhibits IDO1 expression in PDAC cells. Using athymic nude mice, we demonstrate that carbidopa-mediated suppression of IDO1 expression attenuates tumor growth. Mechanistically, we show that AhR is responsible for carbidopa-mediated suppression of IDO1, directly as a transcription factor and indirectly by interfering with the JAK/STAT pathway. Overall, targeting IDO1 not only in immune cells but also in cancer cells could be a beneficial therapeutic strategy for PDAC and potentially for other cancers as well and that carbidopa could be repurposed to treat cancers that overexpress IDO1.

Large gastroduodenal artery pseudoaneurysm and arterioportal fistula in chronic pancreatitis.

Visceral artery pseudoaneurysms, particularly those in the gastroduodenal artery (GDA), are rare but serious complications associated with chronic pancreatitis, posing a significant risk of rupture due to their structural fragility. In this case, a 61-year-old male with a history of chronic pancreatitis, alcohol cirrhosis, duodenal ulcer, and COPD presented with persistent abdominal pain and recurrent fevers. Imaging revealed a 7 cm pseudoaneurysm between the GDA and superior mesenteric vein, which was successfully treated with coil embolization. This case highlights the importance of prompt recognition and intervention in managing GDA pseudoaneurysms, particularly when complicated by an arterioportal fistula, and demonstrates the efficacy of endovascular therapy as a minimally invasive treatment option that can significantly improve patient outcomes in complex vascular complications associated with chronic pancreatitis.

Complex management of concurrent lower extremity arteriovenous malformations: A case study and review of interventional techniques.

Arteriovenous malformations (AVMs) are rare vascular anomalies that present complex diagnostic and therapeutic challenges, particularly in uncommon locations such as the lower extremities. A 72-year-old female with chronic atrial fibrillation, hypertension, and peripheral vascular disease presented with severe lower extremity edema due to multiple AVMs below the knee. This case underscores the importance of a multidisciplinary, individualized approach in managing complex AVMs and highlights the need for advanced imaging and diverse interventional techniques to ensure effective treatment and long-term outcomes.

Access and reattachment of biliary tree anomaly through Roux-en-Y hepaticojejunostomy: A case report.

The right posterior segmental duct (RPSD) draining into the cystic duct is exceedingly rare. Ligation of the cystic duct in proximity to the junction of an aberrant right hepatic duct after a cholecystectomy can lead to life threatening complications. The present case study reveals a severed anomalous RPSD and subsequent Roux-en-Y hepaticojejunostomy procedure employed to fix biliary anomaly.

Unusual presentation of a splenic infarction.

A 41-year-old male with a history of tobacco and alcohol use presented to our clinic for a follow up of an incidentally diagnosed splenic mass. The patient was sent for further diagnostic evaluation, and computed tomography showed a large splenic mass with heterogenous enhancement raising concern for neoplasm. Due to the uncertain nature of the splenic lesion and high complication rate of percutaneous splenic biopsy, a splenectomy was performed. The specimen was sent to pathology, and the report favored neoplasm but was inconclusive. The samples were sent to another institution for a consult, where the patient's spleen was determined to be the result of a previously suffered hemorrhagic infarct. This case demonstrates the difficulty of diagnosing splenic lesions using diagnostic imaging and the discrepancy that may occur between radiology and pathology assessments. In the setting of uncertain pathology, the removal of what might be a functional spleen is often preferred over a percutaneous biopsy due to concerns of intraabdominal bleeding and tumor dissemination.