Vastus Lateralis Muscle Flap for High-Risk Patients Undergoing Orthopaedic Hip Surgery.

INTRODUCTION: Chronic infections and soft-tissue defects are serious complications after total hip arthroplasties (THAs) that may require hip disarticulation (HD). HD is a relatively high-risk procedure with poor long-term outcomes and survival. This is the first study to analyze the effect of an ipsilateral, pedicled vastus lateralis (VL) muscle flap in preventing HD in patients with recurrent complications after THA. METHODS: This retrospective case review analyzed the 6-month postoperative outcomes of 14 patients who underwent soft-tissue hip reconstruction with a VL muscle flap by a single surgeon. RESULTS: Most (86%) patients fully recovered after 6 months with preserved hip range of motion, no pain, and no weakness on ambulation. Two (14%) patients ultimately required HD despite introducing a VL flap. DISCUSSION: A VL muscle flap is an effective treatment of nonhealing THA and prophylactic intervention for patients at high risk for HD. The VL muscle is optimal because of its large size allowing reduction of soft-tissue dead space, its local anatomical location to the hip, and its exceptional vascularity. Additional prospective studies are necessary to determine the most appropriate population for this technique.

A Novel Orthoplastic Reconstruction of Relapsed Clubfoot With Total Ankle Arthroplasty.

Congenital clubfoot is addressed in infancy and rarely persists into adulthood. Ankle arthroplasty is an increasingly popular surgical intervention for patients with ankle arthritis since it allows a natural ankle range of motion and completely replaces a degenerative hindfoot. Here, we describe the first successful total ankle arthroplasty (TAA) for a patient with previously treated congenital clubfoot that reverted later in life. To address the patient's poor soft-tissue integument and reduce the likelihood of post-surgical complications, a perioperative latissimus muscle-free flap was performed. This two-staged, novel orthoplastic intervention addressed our patient's ankle issues and appears to be a viable option for clubfoot patients.

Recent Trends and Future Directions for the Integrated Plastic Surgery Match.

The integrated plastic surgery residency match has risen to be the most competitive specialty in the 2022 match. This reality has prompted medical students to reach a high level of personal achievements, including pursuing research fellowships to boost research productivity. The competitive nature of this specialty has highlighted several barriers for applicants, such as those from groups underrepresented in surgery, of lower socioeconomic backgrounds, or without a home program. In recent years, there have been several changes to the match that stand to attenuate disparities among applicants, such as the transition to virtual interviews and the shift of the United States Medical Licensing Examination Step 1 score to pass-fail. The introduction of the Plastic Surgery Common Application and standardized letters of recommendation has altered the application process for the plastic surgery match. Given these recent trends, evaluating the current landscape and looking toward future directions for the integrated plastic surgery match becomes necessary. Understanding these changes will not only benefit medical students by giving them a transparent look into the match process but also provide a framework for other specialties to follow to increase accessibility to their specific specialty.

α,ω-Diacyl-Substituted Analogues of Natural and Unnatural Polyamines: Identification of Potent Bactericides That Selectively Target Bacterial Membranes.

In this study, α-ω-disubstituted polyamines exhibit a range of potentially useful biological activities, including antimicrobial and antibiotic potentiation properties. We have prepared an expanded set of diarylbis(thioureido)polyamines that vary in central polyamine core length, identifying analogues with potent methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Acinetobacter baumannii and Candida albicans growth inhibition properties, in addition to the ability to enhance action of doxycycline towards Gram-negative bacterium Pseudomonas aeruginosa. The observation of associated cytotoxicity/hemolytic properties prompted synthesis of an alternative series of diacylpolyamines that explored aromatic head groups of varying lipophilicity. Examples bearing terminal groups each containing two phenyl rings (15a-f, 16a-f) were found to have optimal intrinsic antimicrobial properties, with MRSA being the most susceptible organism. A lack of observed cytotoxicity or hemolytic properties for all but the longest polyamine chain variants identified these as non-toxic Gram-positive antimicrobials worthy of further study. Analogues bearing either one or three aromatic-ring-containing head groups were either generally devoid of antimicrobial properties (one ring) or cytotoxic/hemolytic (three rings), defining a rather narrow range of head group lipophilicity that affords selectivity for Gram-positive bacterial membranes versus mammalian. Analogue 15d is bactericidal and targets the Gram-positive bacterial membrane.

Investigation of α,ω-Disubstituted Polyamine-Cholic Acid Conjugates Identifies Hyodeoxycholic and Chenodeoxycholic Scaffolds as Non-Toxic, Potent Antimicrobials.

With the increased incidence of antibiotic resistance, the discovery and development of new antibacterials is of increasing importance and urgency. The report of the natural product antibiotic squalamine in 1993 has stimulated a lot of interest in the study of structurally simplified cholic acid-polyamine derivatives. We report the synthesis of a focused set of deoxycholic acid-polyamine conjugates and the identification of hyodeoxycholic acid derivatives as being potently active towards S. aureus MRSA and some fungal strains, but with no attendant cytotoxicity or hemolytic properties. Analogue 7e exhibited bactericidal activity towards a range of Gram-positive bacteria, while preliminary investigation of its mechanism of action ruled out the bacterial membrane as being a primary cellular target as determined using an ATP-release bioluminescence assay.

PGC-1ß and ERRα Promote Glutamine Metabolism and Colorectal Cancer Survival via Transcriptional Upregulation of PCK2.

BACKGROUND: Previous studies have shown that Peroxisome Proliferator-Activated Receptor Gamma, Coactivator 1 Beta (PGC-1ß) and Estrogen-Related Receptor Alpha (ERRα) are over-expressed in colorectal cancer and promote tumor survival. METHODS: In this study, we use immunoprecipitation of epitope tagged endogenous PGC-1ß and inducible PGC-1ß mutants to show that amino acid motif LRELL on PGC-1ß is responsible for the physical interaction with ERRα and promotes ERRα mRNA and protein expression. We use RNAsequencing to determine the genes regulated by both PGC-1ß & ERRα and find that mitochondrial Phosphoenolpyruvate Carboxykinase 2 (PCK2) is the gene that decreased most significantly after depletion of both genes. RESULTS: Depletion of PCK2 in colorectal cancer cells was sufficient to reduce anchorage-independent growth and inhibit glutamine utilization by the TCA cycle. Lastly, shRNA-mediated depletion of ERRα decreased anchorage-independent growth and glutamine metabolism, which could not be rescued by plasmid derived expression of PCK2. DISCUSSION: These findings suggest that transcriptional control of PCK2 is one mechanism used by PGC-1ß and ERRα to promote glutamine metabolism and colorectal cancer cell survival.