A Collagen10a1 mutation disrupts cell polarity in a medaka model for metaphyseal chondrodysplasia type Schmid.

Heterozygous mutations in COL10A1 lead to metaphyseal chondrodysplasia type Schmid (MCDS), a skeletal disorder characterized by epiphyseal abnormalities. Prior analysis revealed impaired trimerization and intracellular retention of mutant collagen type X alpha 1 chains as cause for elevated endoplasmic reticulum (ER) stress. However, how ER stress translates into structural defects remained unclear. We generated a medaka (Oryzias latipes) MCDS model harboring a 5 base pair deletion in col10a1, which led to a frameshift and disruption of 11 amino acids in the conserved trimerization domain. col10a1Δ633a heterozygotes recapitulated key features of MCDS and revealed early cell polarity defects as cause for dysregulated matrix secretion and deformed skeletal structures. Carbamazepine, an ER stress-reducing drug, rescued this polarity impairment and alleviated skeletal defects in col10a1Δ633a heterozygotes. Our data imply cell polarity dysregulation as a potential contributor to MCDS and suggest the col10a1Δ633a medaka mutant as an attractive MCDS animal model for drug screening.

Inpatient opioid use and pain control after robotic versus laparoscopic sleeve gastrectomy.

BACKGROUND: During the past decade, the proportion of bariatric surgery performed robotically has been rising. However, the clinical benefits of the robotic approach over laparoscopy are uncertain. One area in need of further investigation is pain control after robotic versus laparoscopic bariatric surgery. METHODS: A retrospective cohort study was conducted of bariatric surgery patients undergoing laparoscopic or robotic sleeve gastrectomy at a single institution from October 2019 to August 2022. Inpatient opioid use was measured in morphine milliequivalents. Pain scores were collected by the nursing staff. RESULTS: A total of 368 patients were included: 286 laparoscopic and 82 robotic surgery patients. The groups shared similar demographics. For the entire cohort, the mean age was 42 years, the body mass index was 50 kg/m2, and 79% were female. Mean operative time was significantly lower for laparoscopic surgeries (87.5 ± 47.3 minutes vs 109.3 ± 30.3 minutes; P < .01). The median total inpatient morphine milligram equivalents used was similar for both groups: 52.3 (31.5-77.0) for the laparoscopic group versus 40 (24-74.5) for robotic (P = .13). Mean postoperative pain scores (scale out of 10) were not significantly different between groups: 5.2 ± 1.7 (postoperative day 0) and 4.5 ± 1.7 (day 1) for laparoscopic patients versus 5.1 ± 2.0 (day 0) and 4.4 ± 1.8 (day 1) for robotic. The proportion of patients prescribed opioids at discharge was significantly higher for the laparoscopic group (75.2% vs 62.2%; P = .02). Other clinical outcomes, including duration of stay, 30-day readmissions, and visits to the emergency department, were not significantly different. CONCLUSION: There is no difference in inpatient opioid use or pain scores between patients undergoing laparoscopic and robotic sleeve gastrectomy.

Ultrasmall Bi/Cu Coordination Polymer Combined with Glucose Oxidase for Tumor Enhanced Chemodynamic Therapy by Starvation and Photothermal Treatment.

Multi-modal combination therapy for tumor is expected to have superior therapeutic effect compared with monotherapy. In this study, a super-small bismuth/copper-gallic acid coordination polymer nanoparticle (BCN) protected by polyvinylpyrrolidone is designed, which is co-encapsulated with glucose oxidase (GOX) by phospholipid to obtain nanoprobe BCGN@L. It shows that BCN has an average size of 1.8 ± 0.7 nm, and photothermal conversion of BCGN@L is 31.35% for photothermal imaging and photothermal therapy (PTT). During the treatment process of 4T1 tumor-bearing nude mice, GOX catalyzes glucose in the tumor to generate gluconic acid and hydrogen peroxide (H2 O2 ), which reacts with copper ions (Cu2+ ) to produce toxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and new fresh oxygen (O2 ) to supply to GOX for further catalysis, preventing tumor hypoxia. These reactions increase glucose depletion for starvation therapy , decrease heat shock protein expression, and enhance tumor sensitivity to low-temperature PTT. The in vitro and in vivo results demonstrate that the combination of CDT with other treatments produces excellent tumor growth inhibition. Blood biochemistry and histology analysis suggests that the nanoprobe has negligible toxicity. All the positive results reveal that the nanoprobe can be a promising approach for incorporation into multi-modal anticancer therapy.

Bariatric Surgeon Ergonomics: A Comparison of Laparoscopy and Robotics.

INTRODUCTION: Bariatric surgery is routinely performed using laparoscopic and robotic approaches. Musculoskeletal injuries are prevalent among both robotic and laparoscopic bariatric surgeons. Studies evaluating ergonomic differences between laparoscopic and robotic bariatric surgery are limited. This study aims to analyze the ergonomic, physical, and mental workload differences among surgeons performing robotic and laparoscopic bariatric surgery. MATERIALS AND METHODS: All primary laparoscopic and robotic bariatric surgeries, Roux-en-Y gastric bypass, and sleeve gastrectomy between May and August 2022 were included in this study. Objective ergonomic analysis was performed by an observer evaluating each surgeon intraoperatively according to the validated Rapid Entire Body Assessment tool, with a higher score indicating more ergonomic strain. After each operation, surgeons subjectively evaluated their physical workload using the body part discomfort scale, and their mental workload using the surgery task load index. RESULTS: Five bariatric surgeons participated in this study. In total, 50 operative cases were observed, 37 laparoscopic and 13 robotic. The median total Rapid Entire Body Assessmentscore as a primary surgeon was significantly higher in laparoscopic (6.0) compared to robotic (3.0) cases (P < 0.01). The laparoscopic and robotic approaches had no significant differences in the surgeons' physical (body part discomfort scale) or mental workload (surgery task load index). CONCLUSIONS: This study identified low-risk ergonomic stress in surgeons performing bariatric surgery robotically compared to medium-risk stress laparoscopically. Since ergonomic stress can exist even without the perception of physical or mental stress, this highlights the importance of external observations to optimize ergonomics for surgeons in the operating room.

Characterization of Fibrodysplasia Ossificans Progessiva relevant Acvr1/Acvr2 Activin receptors in medaka (Oryzias latipes).

Activin and Bone Morphogenetic Protein (BMP) signaling plays crucial roles in vertebrate organ formation, including osteo- and angiogenesis, and tissue homeostasis, such as neuronal maintenance. Activin and BMP signaling needs to be precisely controlled by restricted expression of shared receptors, stoichiometric composition of receptor-complexes and presence of regulatory proteins. A R206H mutation in the human (hs) BMP type I receptor hsACVR1, on the other hand, leads to excessive phosphorylation of Sons of mothers against decapentaplegic (SMAD) 1/5/8. This in turn causes increased inflammation and heterotopic ossification in soft tissues of patients suffering from Fibrodysplasia Ossificans Progressiva (FOP). Several animal models have been established to understand the spontaneous and progressive nature of FOP, but often have inherent limitations. The Japanese medaka (Oryzias latipes, ola) has recently emerged as popular model for bone research. To assess whether medaka is suitable as a potential FOP animal model, we determined the expression of Activin receptor type I (ACVR1) orthologs olaAcvr1 and olaAcvr1l with that of Activin type II receptors olaAcvr2ab, olaAcvr2ba and olaAcvr2bb in embryonic and adult medaka tissues by in situ hybridization. Further, we showed that Activin A binding properties are conserved in olaAcvr2, as are the mechanistic features in the GS-Box of both olaAcvr1 and olaAcvr1l. This consequently leads to FOP-typical elevated SMAD signaling when the medaka type I receptors carry the R206H equivalent FOP mutation. Together, this study therefore provides experimental groundwork needed to establish a unique medaka model to investigate mechanisms underlying FOP.

Implementation of a standardized multimodal pain regimen significantly reduces postoperative inpatient opioid utilization in patients undergoing bariatric surgery.

BACKGROUND: Routine opioid use in surgical patients has received attention given the opioid epidemic and a renewed focus on the dangers and drawbacks of opioids in the postoperative setting. Little is known about opioid use in bariatric surgery, especially in the inpatient setting. We hypothesize that a standardized opioid-sparing protocol reduces postoperative inpatient opioid use in bariatric surgery patients. METHODS: A retrospective cohort study was conducted of bariatric surgery patients at a single institution. From March to September 2019, a standardized intraoperative and postoperative opioid-sparing protocol was designed and implemented along with an educational program for patients regarding safe pain management. Inpatient opioid utilization in patients undergoing surgery in the preintervention phase between April and March 2019 was compared to patients from a postintervention phase of October 2019 to December 2020. Opioid utilization was measured in morphine milliequivalents (MME). RESULTS: A total of 359 patients were included; 192 preintervention and 167 postintervention. Patients were similar demographically. For all patients, mean age was 44.1 years, mean BMI 49.2 kg/m2, and 80% were female. Laparoscopic sleeve gastrectomy was performed in 48%, laparoscopic gastric bypass in 34%, robotic sleeve gastrectomy in 17%, and robotic gastric bypass in 1%. In the postintervention phase inpatient opioid utilization was significantly lower [median 134.8 [79.0-240.8] MME preintervention vs. 61.5 [35.5-150.0] MME postintervention (p < 0.001)]. MME prescribed at discharge decreased from a median of 300 MME preintervention to 75 MME postintervention (p < 0.001). In the postintervention phase, 16% of patients did not receive an opioid prescription at discharge compared to 0% preintervention (p < 0.001). When examining by procedure, statistically significant reductions in opioid utilization were seen for each operation. CONCLUSION: Implementation of a standardized intraoperative and postoperative multimodal pain regimen and educational program significantly reduces inpatient opioid utilization in patients undergoing bariatric surgery.

A non-disruptive and efficient knock-in approach allows fate tracing of resident osteoblast progenitors during repair of vertebral lesions in medaka.

During bone development and repair, osteoblasts are recruited to bone deposition sites. To identify the origin of recruited osteoblasts, cell lineage tracing using Cre/loxP recombination is commonly used. However, a confounding factor is the use of transgenic Cre drivers that do not accurately recapitulate endogenous gene expression or the use of knock-in Cre drivers that alter endogenous protein activity or levels. Here, we describe a CRISPR/Cas9 homology-directed repair knock-in approach that allows efficient generation of Cre drivers controlled by the endogenous gene promoter. In addition, a self-cleaving peptide preserves the reading frame of the endogenous protein. Using this approach, we generated col10a1p2a-CreERT2 knock-in medaka and show that tamoxifen-inducible CreERT2 efficiently recombined loxP sites in col10a1 cells. Similar knock-in efficiencies were obtained when two unrelated loci (osr1 and col2a1a) were targeted. Using live imaging, we traced the fate of col10a1 osteoblast progenitors during bone lesion repair in the medaka vertebral column. We show that col10a1 cells at neural arches represent a mobilizable cellular source for bone repair. Together, our study describes a previously unreported strategy for precise cell lineage tracing via efficient and non-disruptive knock-in of Cre.

Microbiologic risk factors of recurrent choledocholithiasis post-endoscopic sphincterotomy.

BACKGROUND: Choledocholithiasis is a severe disorder that affects a significant portion of the world's population. Treatment using endoscopic sphincterotomy (EST) has become widespread; however, recurrence post-EST is relatively common. The bile microbiome has a profound influence on the recurrence of choledocholithiasis in patients after EST; however, the key pathogens and their functions in the biliary tract remain unclear. AIM: To investigate the biliary microbial characteristics of patients with recurrent choledocholithiasis post-EST, using next-generation sequencing. METHODS: This cohort study included 43 patients, who presented with choledocholithiasis at the Guangdong Second Provincial General Hospital between May and June 2020. The patients had undergone EST or endoscopic papillary balloon dilation and were followed up for over a year. They were divided into either the stable or recurrent groups. We collected bile samples and extracted microbial DNA for analysis through next-generation sequencing. Resulting sequences were analyzed for core microbiome and statistical differences between the diagnosis groups; they were examined using the Kyoto Encyclopedia of Genes and Genomes pathway hierarchy level using analysis of variance. Correlation between the key genera and metabolic pathways in bile, were analyzed using Pearson's correlation test. RESULTS: The results revealed distinct clustering of biliary microbiota in recurrent choledocholithiasis. Higher relative abundances (RAs) of Fusobacterium and Neisseria (56.61% ± 14.81% vs 3.47% ± 1.10%, 8.95% ± 3.42% vs 0.69% ± 0.32%, respectively) and the absence of Lactobacillus were observed in the bile of patients with recurrent disease, compared to that in stable patients. Construction of a microbiological co-occurrence network revealed a mutual relationship among Fusobacterium, Neisseria, and Leptotrichia, and an antagonistic relationship among Lactobacillales, Fusobacteriales, and Clostridiales. Functional prediction of biliary microbiome revealed that the loss of transcription and metabolic abilities may lead to recurrent choledocholithiasis. Furthermore, the prediction model based on the RA of Lactobacillales in the bile was effective in identifying the risk of recurrent choledocholithiasis (P = 0.03). CONCLUSION: We demonstrated differences in the bile microbiome of patients with recurrent choledocholithiasis compared to that in patients with stable disease, thereby adding to the current knowledge on its microbiologic etiology.

Examination of abdominal wall perfusion using varying suture techniques for midline abdominal laparotomy closure.

BACKGROUND: With a growing interest in the primary prevention of incisional hernias, it has been hypothesized that different suturing techniques may cause various levels of tissue ischemia. Using ICG laser-induced fluorescence angiography (ICG-FA), we studied the effect of different suture materials and closure techniques on abdominal wall perfusion. METHODS: Fifteen porcine subjects underwent midline laparotomy, bilateral skin flap creation, and three separate 7 cm midline fascial incisions. Animals underwent fascial closure with 5 different techniques: (1) Running 0-PDS® II (polydioxanone) Suture with large bites; (2) Running 0-PDS II Suture with small bites; (3) Interrupted figure-of-eight (8) PDS II Suture, (4) Running 0-barbed STRATAFIX™ Symmetric PDS™ Plus Knotless Tissue Control Device large bite; (5) Running 0-STRATAFIX Symmetric PDS Plus Device small bites. ICG-FA signal intensity was recorded prior to fascial incision (baseline), immediately following fascial closure (closure), and at one-week (1-week.). Post-mortem, the abdominal walls were analyzed for inflammation, neovascularity, and necrosis. RESULTS: PDS II Suture with small bites, fascial closure at the caudal 1/3 of the abdominal wall, and the 1-week time period were all independently associated with increased tissue perfusion. There was also a significant increase in tissue perfusion from closure to 1-week when using small bites PDS II Suture compared to PDS II Suture figure-of-8 (p < 0.001) and a trend towards significance when compared with large bites PDS II Suture (p = 0.056). Additionally, the change in perfusion from baseline to 1 week with small bites was higher than with figure of 8 (p = 0.002). Across all locations, small bite PDS II Suture has greater total inflammation than figure of 8 (p < 0.001). CONCLUSIONS: The results suggest that the small bite technique increases abdominal wall perfusion and ICG-FA technology can reliably map abdominal wall perfusion. This finding may help explain the reduced incisional hernia rates seen in clinical studies with the small bite closure technique.

Assessment of postoperative opioid stewardship using a novel electronic-based automated text and phone messaging platform.

BACKGROUND: Practices of opioid prescribing vary widely across general surgery providers. The goal of this study was to use a text-based platform to assess postdischarge opioid utilization. METHODS: A prospective, cohort study enrolled adult patients undergoing operations across the following 3 general surgery sections: minimally invasive surgery, colorectal, and surgical oncology. Using Epharmix, an electronic text-based platform, short message service text messages were sent to enrolled patients on postdischarge days 1 to 7, 14, 2, and 28 inquiring about the number of opioid pills taken since discharge and pain medication refills. RESULTS: A total of 253 patients enrolled and completed the intervention. Patient participation was robust, with 80% of patients responded to >50% of all text-based questions, and 64% responded to >80% of all questions. Patients undergoing bariatric surgery were prescribed the most narcotic pain medications (average milligram of morphine equivalents: 250.8), and those undergoing endocrine neck surgery the least (average milligram of morphine equivalent: 53.5). All surgical categories studied consumed ≤25% of their total prescribed milligram of morphine equivalents. Only 8 patients (3.2%) requested an opioid refill by postdischarge days 28. CONCLUSION: A text-based platform can track reliably patients' opioid usage postdischarge. Such platforms may facilitate the development of data-driven, standardized practices of opioid prescribing matched to patients' anticipated opioid usage postdischarge.

Macrophages Switch to an Osteo-Modulatory Profile Upon RANKL Induction in a Medaka (Oryzias latipes) Osteoporosis Model.

In mammals, osteoclasts differentiate from macrophages in the monocyte lineage. Although many factors driving osteoclast formation are known, the detailed processes underlying precursor recruitment, differentiation, and interaction of macrophages with other cell types involved in bone remodeling are poorly understood. Using live imaging in a transgenic medaka osteoporosis model, where ectopic osteoclasts are induced by RANKL expression, we show that a subset of macrophages is recruited to bone matrix to physically interact with bone-forming osteoblast progenitors. These macrophages subsequently differentiate into cathepsin K- (ctsk-) positive osteoclasts. One day later, other macrophages are recruited to clear dying osteoclasts from resorbed bone by phagocytosis. To better understand the molecular changes underlying these dynamic processes, we performed transcriptome profiling of activated macrophages upon RANKL induction. This revealed an upregulation of several bone-related transcripts. Besides osteoclast markers, we unexpectedly also found expression of osteoblast-promoting signals in activated macrophages, suggesting a possible non-cell autonomous role in osteogenesis. Finally, we show that macrophage differentiation into osteoclasts is dependent on inflammatory signals. Medaka deficient for TNFα or treated with the TNFα-inhibitor pentoxifylline exhibited impaired macrophage recruitment and osteoclast differentiation. These results show the involvement of inflammatory signals and the dynamics of a distinct subset of macrophages during osteoclast formation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Cxcl9l and Cxcr3.2 regulate recruitment of osteoclast progenitors to bone matrix in a medaka osteoporosis model.

Bone homeostasis requires continuous remodeling of bone matrix to maintain structural integrity. This involves extensive communication between bone-forming osteoblasts and bone-resorbing osteoclasts to orchestrate balanced progenitor cell recruitment and activation. Only a few mediators controlling progenitor activation are known to date and have been targeted for intervention of bone disorders such as osteoporosis. To identify druggable pathways, we generated a medaka (Oryzias latipes) osteoporosis model, where inducible expression of receptor-activator of nuclear factor kappa-Β ligand (Rankl) leads to ectopic formation of osteoclasts and excessive bone resorption, which can be assessed by live imaging. Here we show that upon Rankl induction, osteoblast progenitors up-regulate expression of the chemokine ligand Cxcl9l. Ectopic expression of Cxcl9l recruits mpeg1-positive macrophages to bone matrix and triggers their differentiation into osteoclasts. We also demonstrate that the chemokine receptor Cxcr3.2 is expressed in a distinct subset of macrophages in the aorta-gonad-mesonephros (AGM). Live imaging revealed that upon Rankl induction, Cxcr3.2-positive macrophages get activated, migrate to bone matrix, and differentiate into osteoclasts. Importantly, mutations in cxcr3.2 prevent macrophage recruitment and osteoclast differentiation. Furthermore, Cxcr3.2 inhibition by the chemical antagonists AMG487 and NBI-74330 also reduced osteoclast recruitment and protected bone integrity against osteoporotic insult. Our data identify a mechanism for progenitor recruitment to bone resorption sites and Cxcl9l and Cxcr3.2 as potential druggable regulators of bone homeostasis and osteoporosis.

Lineage tracing of col10a1 cells identifies distinct progenitor populations for osteoblasts and joint cells in the regenerating fin of medaka (Oryzias latipes).

The caudal fin of teleost fish regenerates fully within two weeks of amputation. While various cell lineages have been identified and characterized in the regenerating fin, the origin of bone cells remains debated. Here, we analysed collagen10a1 (col10a1) expressing cells in the regenerating fin of the medaka (Oryzias latipes) and tested whether they represent an alternative progenitor source for regenerating osteoblasts. Under normal conditions, col10a1 cells are positioned along fin ray segments and in intersegmental regions. Lineage tracing in the amputated fin revealed that col10a1 cells from the stump contribute to the regenerating bony fin rays. However, ablation of col10a1 cells did not abolish fin regeneration suggesting that col10a1 expressing osteoblast progenitors are dispensable for regeneration. Intriguingly, however, after ablation of osterix (osx)/sp7-col10a1 double-positive osteoblasts, col10a1 cells exclusively gave rise to joint cells in the intersegmental region thus identifying a pool of lineage-restricted joint progenitor cells. To identify additional sources for regenerating osteoblasts, we performed clonal lineage analysis. Our data provide the first evidence that after ablation of mature osteoblasts in medaka, transdifferentiation does not account for de novo osteoblast generation. Instead, our findings suggest the presence of lineage restricted progenitor pools in medaka, similar to the situation in zebrafish. After osteoblast ablation, these pools become activated and give rise to fin ray osteoblasts and intersegmental joint cells during regeneration. In summary, we conclude that col10a1-positive cells do not represent an exclusive source for osteoblasts but are progenitors of joint cells in the regenerating fin.

Postoperative opioid prescribing practices and the impact of the hydrocodone schedule change.

BACKGROUND: In 2014, hydrocodone was moved from Schedule III to II, thus it could no longer be "called in" to a pharmacy. We analyzed current postoperative opioid prescribing patterns and the impact of the schedule change on the type and amount prescribed. METHODS: Opioid prescriptions for common surgeries at 1 medical center from 2013 to 2016 were analyzed retrospectively. Milligram morphine equivalents prescribed before and after the schedule change were compared by t tests, and interrupted time series models and drug frequencies were compared by χ2 and Fisher exact tests. RESULTS: Data from 7,046 patients (7,361 prescriptions) after 29 different operations were analyzed. Milligram morphine equivalents prescribed for minor open procedures ranged from 211 to 342 milligram morphine equivalents, from 323 to 1297 for major open procedures, from 238 to 359 for basic laparoscopic procedures, and from 221 to 868 for complex laparoscopic procedures. Mean milligram morphine equivalents prescribed were not affected for most procedures, but over the entire population, milligram morphine equivalents prescribed began decreasing after the rule change. The percentage of hydrocodone prescriptions decreased after the rule change (from 33.8% down to 27.0%) and oxycodone and tramadol prescriptions increased. CONCLUSION: Before versus after the rule change, hydrocodone prescriptions decreased and oxycodone and tramadol prescriptions increased. Milligram morphine equivalents prescribed varied considerably across and within classes of procedures, but the schedule change did not affect mean milligram morphine equivalents prescribed for most procedures.

Opioid Medication Use in the Surgical Patient: An Assessment of Prescribing Patterns and Use.

BACKGROUND: With the epidemic of prescription opioid abuse in the US, rates of opioid-related unintentional deaths have risen dramatically. However, few data exist comparing postoperative opioid prescriptions with patient use. We sought to better elucidate this relationship in surgical patients. STUDY DESIGN: A prospective cohort study was conducted of narcotic-naïve patients undergoing open and laparoscopic abdominal procedures on a minimally invasive surgery service. During the first 14 post-discharge days and at their first postoperative clinic visit, patients recorded pain scores and number of opioid pills taken. Clinical data were extracted from the medical record. Descriptive statistics were used in data analysis. RESULTS: From 2014 through 2017, one hundred and seventy-six patients completed postoperative pain surveys. Mean age was 60.4 ± 14.9 years and sex was distributed equally. Most patients (69.9%) underwent laparoscopic procedures. Hydrocodone-acetaminophen was the most commonly prescribed postoperative pain medication (118 patients [67.0%]), followed by oxycodone-acetaminophen (26 patients [14.8%]). Patients were prescribed a median of 150 morphine milligram equivalents (MME) (interquartile range [IQR] 150 to 225 MME), equivalent to twenty 5-mg oral oxycodone pills (IQR 20 to 30 pills). However, by their first postoperative visit, they had only taken a median 30 MME (IQR 10 to 90 MME), or 4 pills (IQR 1.3 to 12 pills). Eight (4.5%) patients received a refill or an additional prescription for pain medications. At the first postoperative visit, 76.7% of respondents were satisfied or very satisfied with their overall postoperative pain management. CONCLUSIONS: Postoperative patients might consume less than half of the opioid pills they are prescribed. More research is needed to standardize opioid prescriptions for postoperative pain management while reducing opioid diversion.

Combined in vivo and ex vivo analysis of mesh mechanics in a porcine hernia model.

BACKGROUND: Hernia meshes exhibit variability in mechanical properties, and their mechanical match to tissue has not been comprehensively studied. We used an innovative imaging model of in vivo strain tracking and ex vivo mechanical analysis to assess effects of mesh properties on repaired abdominal walls in a porcine model. We hypothesized that meshes with dissimilar mechanical properties compared to native tissue would alter abdominal wall mechanics more than better-matched meshes. METHODS: Seven mini-pigs underwent ventral hernia creation and subsequent open repair with one of two heavyweight polypropylene meshes. Following mesh implantation with attached radio-opaque beads, fluoroscopic images were taken at insufflation pressures from 5 to 30 mmHg on postoperative days 0, 7, and 28. At 28 days, animals were euthanized and ex vivo mechanical testing performed on full-thickness samples across repaired abdominal walls. Testing was conducted on 13 mini-pig controls, and on meshes separately. Stiffness and anisotropy (the ratio of stiffness in the transverse versus craniocaudal directions) were assessed. RESULTS: 3D reconstructions of repaired abdominal walls showed stretch patterns. As pressure increased, both meshes expanded, with no differences between groups. Over time, meshes contracted 17.65% (Mesh A) and 0.12% (Mesh B; p = 0.06). Mesh mechanics showed that Mesh A deviated from anisotropic native tissue more than Mesh B. Compared to native tissue, Mesh A was stiffer both transversely and craniocaudally. Explanted repaired abdominal walls of both treatment groups were stiffer than native tissue. Repaired tissue became less anisotropic over time, as mesh properties prevailed over native abdominal wall properties. CONCLUSIONS: This technique assessed 3D stretch at the mesh level in vivo in a porcine model. While the abdominal wall expanded, mesh-ingrown areas contracted, potentially indicating stresses at mesh edges. Ex vivo mechanics demonstrate that repaired tissue adopts mesh properties, suggesting that a better-matched mesh could reduce changes to abdominal wall mechanics.

Synthetic versus Biologic Mesh in Single-Stage Repair of Complex Abdominal Wall Defects in a Contaminated Field.

BACKGROUND: Synthetic meshes have been used with varying rates of success in a contaminated setting, although their use is not widely accepted because of concerns for infection. A biologic mesh (BM) is assumed to be more resistant to infection than a synthetic mesh; however, sparse clinical data support this theory. The hypothesis for this study: Uncoated polypropylene synthetic mesh (USM) can be used to obtain a durable repair in the setting of a contaminated abdominal wall reconstruction (AWR) in a single-stage procedure with comparable infectious outcomes to a biologic mesh repair. PATIENTS AND METHODS: We performed a retrospective chart review on contaminated AWR, comparing 34 BM with 24 USM with infection as the primary outcome of interest. Secondary outcomes were re-admission and re-operation. We also investigated the microbial isolates that were cultured. RESULTS: Mesh groups were similar in their demographics, duration of surgery, previous mesh, surgical site class, and source of contamination. Length of stay was 4 d longer in BM, p = 0.01. Overall infection rate was 50% for BM vs. 29.2% for USM, p = 0.18. Treatment in case of infection was similar across both groups. Gram positive bacteria comprised 39% of BM microbiology vs. 63% for USM. Re-admission rate was 52.9% for BM versus 45.8% for USM, p > 0.5. The BMs re-admitted for surgical site infection/abdominal abscess were 38.9% versus 55.6% for USM. No USM were re-admitted for seroma versus 33.3% of BM, p = 0.06. Re-operation rate was 26.5% for BM versus 33.3% for USM, p > 0.5. Procedures performed at re-operation were similar between groups. Regression analysis did not demonstrate an association between mesh type and our outcomes. CONCLUSION: Our results show that synthetic meshes are not inferior to biologic meshes in contaminated AWR. This is important in view of the tremendous cost disparity between these two products and the questionable ability of biologic mesh to offer a durable hernia repair.

Adipose tissue location and contribution to postinjury hypercoagulability.

OBJECTIVES: Obesity is associated with a hypercoagulable state at baseline and following injury. The anatomic location of adipose deposition may influence the type of thrombotic event, with visceral adipose tissue (VAT) associated with arterial thrombosis and subcutaneous adipose tissue (SAT) predisposing to venous thrombosis. We sought to determine whether adipose tissue amount and location correlated with measures of coagulation. METHODS: All adult Level I trauma activations at our institution between January 2013 and August 2014 who underwent admission abdominal computed tomography scan and had admission rotational thromboelastometry measurements were included. Patients were excluded for history of anticoagulant use and known coagulopathy/hypercoagulable state. Admission computed tomography was used to obtain cross-sectional VAT and SAT areas at the umbilicus utilizing a novel software system; VAT and SAT measurements were associated with markers of coagulation utilizing Spearman correlation and stepwise linear regression with significance set at p < 0.05. RESULTS: Two hundred forty-two patients met inclusion and exclusion criteria. Sixty-nine percent of patients sustained blunt injury, 79% were male, mean age was 40 years, 25% were obese or morbidly obese, and mean Injury Severity Scale score was 17. Seventeen percent of patients had acute deep venous thrombosis or pulmonary embolism during hospitalization. Neither SAT nor VAT correlated with prothrombin time, international normalized ratio, or partial thromboplastin time. Subcutaneous adipose tissue correlated positively with platelet count. Visceral adipose tissue and SAT correlated negatively with clot formation time and positively with TEM fibrinogen, α angle, maximum clot firmness, and lysis at 30 minutes; stronger correlations and greater significance were seen between SAT and these measures except for lysis at 30 minutes. Stepwise linear regression confirmed significant relationships between SAT and clot formation time, AA, and maximum clot firmness; VAT showed a significant relationship with TEM fibrinogen. CONCLUSIONS: Increased adipose tissue correlates with relative hypercoagulability following trauma. Subcutaneous adipose tissue shows a stronger relationship with functional measures of coagulation, suggesting that SAT may be associated with hemorrhage resistance and hypercoagulability after injury. LEVEL OF EVIDENCE: Prognostic study, level IV.

Perioperative risk and complications of revisional bariatric surgery compared to primary Roux-en-Y gastric bypass.

INTRODUCTION: Growing number of patients requires revisional bariatric surgery. This study compares perioperative course and outcomes of revisional versus primary bariatric surgery. METHODS: Patients who underwent revisional bariatric surgery from Jan 1997 to Sept 2012 were reviewed retrospectively. Every revisional patient with BMI >35 and age <70 was matched with a primary Roux-en-Y gastric bypass control patient based on preoperative BMI, age, sex, and year of surgery. Patients' preoperative indications, intraoperative/postoperative course, and complications were analyzed. RESULTS: Two hundred and fifty five patients underwent revisional bariatric surgery with resulting Roux-en-Y gastric bypass anatomy while 1,674 patients underwent primary gastric bypass in the same time interval. Of 255 patients, 172 patients were paired with 172 primary gastric bypass patients. Revisional bariatric group had preoperative BMI 48 ± 9, age 52 ± 9 years, 93 % female, 44 % laparoscopic, 30 % diabetic, 60 % hypertensive. Primary bypass patients had preoperative BMI 49 ± 8, age 52 ± 9 years, 93 % female, 97 % laparoscopic, 49 % diabetic, 67 % hypertensive. Compared to primary bypass patients, revisional patients had significantly higher estimated blood loss (463.7 vs. 113.3 mL), longer operative time (272.5 vs. 175.5 min), greater risk for ICU stay (N = 24, 14 % vs. N = 2, 1 %), and longer hospital stay (5.6 vs. 2.5 days). There were significantly more intraoperative liver (N = 13, 8 % vs. N = 1, 1 %) and spleen (N = 18, 10 % vs. N = 0) injuries, and more enterotomies (N = 9, 5 % vs. N = 0) in the revisional group. There were also significantly more postoperative complications (N = 94, 55 % vs. N = 48, 28 %), readmissions (N = 27, 16 % vs. N = 12, 7 %), and reoperations (N = 16, 9 % vs. N = 3, 2 %) within 30 days of surgery. Mean percentage weight loss at 1 year was significantly less for revisional patients (27 vs. 37 %). There was no significant difference in 30 day mortality between the two groups (N = 6 vs. 0). CONCLUSION: Even in experienced hands, complex revisional bariatric surgery should be approached with significant caution, especially given that weight loss is less substantial.