Novel "starburst" mesh configuration for paraesophageal and recurrent hiatal hernia repair: comparison with keyhole mesh configuration.

BACKGROUND: Controversy exists over the use of mesh, its type and configuration in repair of hiatal hernia. We have used biological mesh for large or recurrent hiatal hernias. We have developed a mesh configuration to better enhance the tensile strength of the hiatus by folding the mesh over the edge of the hiatus-entitled the "starburst" configuration. We report our experience with the starburst configuration, comparing it to our results with the keyhole configuration. METHODS: Medical records of all patients undergoing either the keyhole or starburst mesh configuration hiatal hernia repair were reviewed between 2017 and 2021. Data gathered included age, sex, type of hernia (sliding, paraesophageal, or recurrent), fundoplication type (none, Nissen, Toupet, Dor, Collis-Nissen, Collis-Toupet, or magnetic sphincter augmentation [MSA]), 30-day complications, and long-term outcomes (hiatal hernia recurrence, reflux-symptom recurrence, dysphagia, dilations, reoperations). RESULTS: From 7/2017 to 8/2019, 51 cases using the keyhole mesh were completed. Sliding hiatal hernia comprised 4%, paraesophageal hernia (PEH) 64% and recurrent hiatal hernia (RHH) 34% of cases. Distribution of fundoplication type: 2% none, 41% Nissen, 41% Toupet, 8% Dor, 2% Collis-Nissen, and 6% Collis-Toupet. 30-day complication rate 31%. Long-term outcomes: recurrent hiatal hernia 16%, dysphagia 12%, dysphagia requiring dilation(s) 10%, recurrent GERD symptoms 4%, and reoperation 14%. From 10/2020 to 8/2021, 58 cases using the starburst configuration were completed. PEH comprised 60% and RHH 40%. Distribution of fundoplication type: 10% none, 40% Nissen, 43% Toupet, 5% MSA, 2% Collis-Toupet. 30-day complication rate 16%. Long-term outcomes: recurrent hiatal hernia 19%, dysphagia 14%, dilations 5%, recurrent GERD symptoms 9%, and reoperations 3%. CONCLUSION: The starburst mesh configuration compares favorably with the keyhole configuration with respect to postoperative dysphagia, need for esophageal dilation, and GERD symptom recurrence, with similar recurrence rates. We are continuing to further refine this technique and study the long-term outcomes.

Autoantibodies targeting TRIM72 compromise membrane repair and contribute to inflammatory myopathy.

Idiopathic inflammatory myopathies (IIM) involve chronic inflammation of skeletal muscle and subsequent muscle degeneration due to an uncontrolled autoimmune response; however, the mechanisms leading to pathogenesis are not well understood. A compromised sarcolemmal repair process could promote an aberrant exposure of intramuscular antigens with the subsequent initiation of an inflammatory response that contributes to IIM. Using an adoptive transfer mouse model of IIM, we show that sarcolemmal repair is significantly compromised in distal skeletal muscle in the absence of inflammation. We identified autoantibodies against TRIM72 (also known as MG53), a muscle-enriched membrane repair protein, in IIM patient sera and in our mouse model of IIM by ELISA. We found that patient sera with elevated levels of TRIM72 autoantibodies suppress sarcolemmal resealing in healthy skeletal muscle, and depletion of TRIM72 antibodies from these same serum samples rescues sarcolemmal repair capacity. Autoantibodies targeting TRIM72 lead to skeletal muscle fibers with compromised membrane barrier function, providing a continuous source of autoantigens to promote autoimmunity and further amplifying humoral responses. These findings reveal a potential pathogenic mechanism that acts as a feedback loop contributing to the progression of IIM.

Multiple poloxamers increase plasma membrane repair capacity in muscle and nonmuscle cells.

Various previous studies established that the amphiphilic tri-block copolymer known as poloxamer 188 (P188) or Pluronic-F68 can stabilize the plasma membrane following a variety of injuries to multiple mammalian cell types. This characteristic led to proposals for the use of P188 as a therapeutic treatment for various disease states, including muscular dystrophy. Previous studies suggest that P188 increases plasma membrane integrity by resealing plasma membrane disruptions through its affinity for the hydrophobic lipid chains on the lipid bilayer. P188 is one of a large family of copolymers that share the same basic tri-block structure consisting of a middle hydrophobic propylene oxide segment flanked by two hydrophilic ethylene oxide moieties [poly(ethylene oxide)80-poly(propylene oxide)27-poly(ethylene oxide)80]. Despite the similarities of P188 to the other poloxamers in this chemical family, there has been little investigation into the membrane-resealing properties of these other poloxamers. In this study we assessed the resealing properties of poloxamers P181, P124, P182, P234, P108, P407, and P338 on human embryonic kidney 293 (HEK293) cells and isolated muscle from the mdx mouse model of Duchenne muscular dystrophy. Cell membrane injuries from glass bead wounding and multiphoton laser injury show that the majority of poloxamers in our panel improved the plasma membrane resealing of both HEK293 cells and dystrophic muscle fibers. These findings indicate that many tri-block copolymers share characteristics that can increase plasma membrane resealing and that identification of these shared characteristics could help guide design of future therapeutic approaches.

NMR-Based Urinary Metabolomics Applications.

The field of metabolomics has been growing tremendously over the recent years and, consistent with that growth, a number of investigators have been looking at the potential of NMR-based urinary metabolomics for several applications. While such applications have shown promising results, there still remains an enormous amount of work to be done before this approach becomes accepted and widely used in clinical diagnostics and other biomedical applications. To achieve such goals, optimization of parameters and standardization of protocols are of paramount importance. In view of this, in this chapter, we present some recommended methods and procedures that can help researchers in the field. Furthermore, we have highlighted some of the challenges encountered in such applications and suggested some possible ways to overcome those challenges.

Diagnostic Applications of Nuclear Magnetic Resonance-Based Urinary Metabolomics.

Metabolomics is a rapidly growing field with potential applications in various disciplines. In particular, metabolomics has received special attention in the discovery of biomarkers and diagnostics. This is largely due to the fact that metabolomics provides critical information related to the downstream products of many cellular and metabolic processes which could provide a snapshot of the health/disease status of a particular tissue or organ. Many of these cellular products eventually find their way to urine; hence, analysis of urine via metabolomics has the potential to yield useful diagnostic and prognostic information. Although there are a number of analytical platforms that can be used for this purpose, this review article will focus on nuclear magnetic resonance-based metabolomics. Furthermore, although there have been many studies addressing different diseases and metabolic disorders, the focus of this review article will be in the following specific applications: urinary tract infection, kidney transplant rejection, diabetes, some types of cancer, and inborn errors of metabolism. A number of methodological considerations that need to be taken into account for the development of a clinically useful optimal test are discussed briefly.