Single-staged retromuscular abdominal wall reconstruction with mesh at the time of ostomy reversal: are we crossing the line? An ACHQC Analysis.

INTRODUCTION: The most appropriate method of reconstructing the abdominal wall at the site of a simultaneous stoma takedown is controversial. The contaminated field, concomitant GI procedure being performed and presence of a hernia all complicate decision-making. We sought to describe the surgical approaches, mesh type and outcomes of concomitant abdominal wall reconstruction during stoma takedown in a large hernia registry. METHODS AND PROCEDURES: All patients who underwent stoma takedown with simultaneous hernia repair with retromuscular mesh placement from January 2014 to May 2022 were identified within the Abdominal Core Health Quality Collaborative (ACHQC). Patients were stratified by mesh type including permanent synthetic (PS), resorbable synthetic (RS) and biologic mesh. Association of mesh type with 30-day wound events and other complications and 1-year outcomes were evaluated. RESULTS: There were 368 patients who met inclusion criteria. Eighty-nine patients had ileostomies, 276 colostomies and 3 had both. Two hundred and seventy-nine (75.8%) patients received PS mesh, 46 (12.5%) biologic, and 43 (11.7%) RS. Seventy percent (259/368) had a parastomal hernia, 75% (285/368) had a midline incisional hernia, and 48% (178/368) had both. All groups had similar preoperative comorbidities and the majority had a transversus abdominus release. All mesh groups had similar thirty-day SSI (13.2-14.3%), SSO (10.5-17.8%) and SSOPI (7.9-14.1%), p = 0.6. Three patients with PS mesh developed infected synthetic mesh and one PS mesh required excision. Four patients with PS developed an enterocutaneous fistula. Of these, only one patient was recorded as having both an enterocutaneous fistula and mesh infection. Thirty-day reoperation and readmission were similar across all mesh groups. Recurrence at 1-year was similar between mesh groups. Quality of life measured using HerQLes scores were higher at one year compared to baseline in all groups indicating improvement in hernia-specific quality of life. CONCLUSION: Early complication rates associated with simultaneous stoma takedown and abdominal wall reconstruction are significant, regardless of mesh type utilized. Concomitant surgery should be weighed heavily and tailored to individual patients.

Epidural analgesia and post-operative ileus after incisional hernia repair with transversus abdominis release: Results of a 5-year quality improvement initiative.

INTRODUCTION: The optimal pain management strategy after open ventral hernia repair (VHR) with transversus abdominus release (TAR) is unknown. Opioids are known to have an inhibitory effect on the GI tract and cause postoperative ileus. Epidural analgesia is associated with lower postoperative ileus rates but may contribute to other postoperative complications. A propensity-matched retrospective review published by our group in 2018 found that epidural analgesia was associated with an increased length of stay and any postoperative complication after VHR. Epidural analgesia was therefore abandoned by our group following this publication. We aimed to determine if discontinuation of epidural analgesia affected ileus rates after open VHR. METHODS: Patients who underwent open VHR with TAR from August 2014 to January 2022 â€‹at Cleveland Clinic Foundation with at least 30-day follow-up were retrospectively identified using the Abdominal Core Health Quality Collaborative registry. Patients with and without epidural analgesia were compared. The primary outcome was post-operative ileus. Additional outcomes included length of stay, deep venous thrombosis (DVT), pneumonia, wound complications and pain requiring intervention. RESULTS: A total of 2570 patients were included: 420 had an epidural, 2150 did not. Preoperative patient and hernia characteristics were similar between both groups. Mean hernia width was 15.5 â€‹cm in the epidural group and 16.1 â€‹cm in the no epidural group. In the epidural group, ileus was seen in 9 of 420 (2.15%) of patients which was significantly less than in the no epidural group, 400 of 2150 (18.6%), p=>0.001. On multivariate analysis, epidurals were predictive of lower risk of ileus (OR 0.04, 95%CI 0.01-0.17, p â€‹= â€‹0.001) and pain requiring intervention (OR 0.02, 95%CI 0.00-0.71, p â€‹= â€‹0.02). Epidural analgesia was not associated with increased DVT rates, pneumonia, length of stay, SSI, or SSOPI. DISCUSSION: Discontinuation of epidural analgesia was associated with a 9-fold increase in ileus rates after VHR with TAR. Epidurals may play an important role in limiting postoperative opioid use and therefore reducing risk of ileus. Other postoperative complications including pneumonia and venous thrombosis were not impacted by epidurals. Further prospective studies are needed to further define a ventral hernia patient population who will benefit from epidural analgesia.

Cost, Operative Delay, and X-Rays for Incorrect Surgical Counts.

At Cleveland clinic, an incorrect surgical count triggers Code Rust; a protocol that mandates an intraoperative patient X-ray, staff radiology read, and discussion with the surgeon before the incision is closed. Code Rust calls from November 2014 to December 2022 were retrospectively reviewed. Realtime workflow and operative details of Code Rust cases were analyzed.1277 Code Rusts were identified. Average time from ordering the X-ray to final radiology report was 50 minutes, totalling $2,362,450.00 spent on operating room time. Code Rust was called twice as frequently during urgent or emergent cases, compared to elective. There were more staff in Code Rust rooms compared to non-Code Rust rooms. A foreign body on X-ray was identified in 42/1277 (3.3%) cases. Code Rust is a resource intensive process that is more common in emergent cases that involve multiple staff. While retained foreign bodies are identified in a small percentage of cases, the current system should be revisited to reduce operating time and expense.

Revisiting femoral hernia diagnosis rates by patient sex in inguinal hernia repairs.

INTRODUCTION: Guidelines recommend MIS repairs for females with inguinal hernias, despite limited evidence. We investigated rates of femoral hernias intraoperatively noted during MIS and Lichtenstein repairs in females. METHODS: ACHQC was queried for adult females undergoing inguinal hernia repair between January 2014-November 2022. Outcomes included identified femoral hernia and size, hernia recurrence, quality of life, and sex-based recurrence. RESULTS: 1357 and 316 females underwent MIS and Lichtenstein inguinal repair respectively. Femoral hernias were identified more frequently in MIS than open repairs (27%vs12%; (p â€‹< â€‹0.001). Most femoral hernias in MIS (61%) and Lichtenstein repairs (62%) were <1.5 â€‹cm(p â€‹< â€‹0.001). Identification rates of femoral hernias >3 â€‹cm were 1% overall(p â€‹= â€‹0.09). Surgeon and patient-reported recurrences were similar between approaches at 1-5-years for females(p â€‹> â€‹0.05 for all) and similar between sexes(p â€‹> â€‹0.05). CONCLUSION: Most incidental femoral hernias are small and both repair approaches demonstrated similar outcomes. The recommendation for MIS inguinal hernia repairs in females is potentially overstated.

Tipping the scale in abdominal wall reconstruction: An analysis of short- and long-term outcomes by body mass index.

BACKGROUND: Morbid obesity, with a body mass index 35 kg/m2, is a commonly used cutoff for denying elective transversus abdominis release. Although obesity is linked to short-term wound morbidity, its effect on long-term outcomes remains unknown, calling into question if a cutoff is justified. We sought to compare 1-year recurrence rates after transversus abdominis release based on body mass index and to evaluate short- and long-term outcomes. METHODS: Patients undergoing open, clean transversus abdominis release from August 2014 to January 2022 at our institution with 1-year follow-up completed were identified. Univariate and multivariable analyses were performed to determine the association of body mass index with 90-day wound events, 1-year hernia recurrence, and hernia-specific quality of life. Covariates included body mass index, diabetes, recurrent hernia, hernia width, fascial closure, surgical site occurrence requiring procedural intervention, previous abdominal wall surgical site infection, inflammatory bowel disease, mesh weight, and mesh-to-hernia size ratio. RESULTS: A total of 1,089 patients were included. Increasing body mass index was associated with surgical site infection (adjusted odds ratio = 1.59; 95% confidence interval, 1.14-1.77; P < .01) and surgical site occurrence (adjusted odds ratio = 1.42; 95% confidence interval, 1.13-1.74; P < .01) but was not associated with surgical site occurrence requiring procedural intervention. Hernia width was associated with surgical site occurrence (adjusted odds ratio = 1.4; 95% confidence interval, 1.08-1.82; P < .01) and surgical site occurrence requiring procedural intervention (adjusted odds ratio = 1.4; 95% confidence interval, 1.08-1.82; P = .01). Hernia recurrence rate at 1 year was lower for the body mass index ≥35 kg/m2 group (7% vs 12%; P = .02). Hernia width (odds ratio = 1.33; 95% confidence interval, 1.02-1.74; P = .04) was associated with recurrence; body mass index was not (P = .11). Both groups experienced significant improvement in hernia-specific quality of life at 1 year. CONCLUSION: Morbid obesity is associated with 90-day wound morbidity; however, short-term complications did not translate to higher reoperation or long-term recurrence rates. The impact of body mass index on hernia recurrence is likely overstated. An arbitrary body mass index cutoff of 35 kg/m2 should not be used to deny symptomatic patients abdominal wall reconstruction.

Does selective intraoperative music reduce pain following abdominal wall reconstruction? A double-blind randomized controlled trial.

PURPOSE: Although intraoperative music is purported to mitigate postoperative pain after some procedures, its application has never been explored in abdominal wall reconstruction (AWR). We sought to determine whether intraoperative music would decrease early postoperative pain following AWR. METHODS: We conducted a placebo-controlled, patient-, surgeon-, and assessor-blinded, randomized controlled trial at a single center between June 2022 and July 2023 including 321 adult patients undergoing open AWR with retromuscular mesh. Patients received noise-canceling headphones and were randomized 1:1 to patient-selected music or silence after induction, stratified by preoperative chronic opioid use. All patients received multimodal pain control. The primary outcome was pain (NRS-11) at 24 ± 3 h. The primary outcome was analyzed by linear regression with pre-specified covariates (chronic opioid use, hernia width, operative time, myofascial release, anxiety disorder diagnosis, and preoperative STAI-6 score). RESULTS: 178 patients were randomized to music, 164 of which were analyzed. 177 were randomized to silence, 157 of which were analyzed. At 24 ± 3 h postoperatively, there was no difference in the primary outcome of NRS-11 scores (5.18 ± 2.62 vs 5.27 ± 2.46, p = 0.75). After adjusting for prespecified covariates, the difference of NRS-11 scores at 24 ± 3 h between the music and silence groups remained insignificant (p = 0.83). There was no difference in NRS-11 or STAI-6 scores at 48 ± 3 and 72 ± 3 h, intraoperative sedation, or postoperative narcotic usage. CONCLUSION: For patients undergoing AWR, there was no benefit of intraoperative music over routine multimodal pain control for early postoperative pain reduction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05374096.

Open Complex Abdominal Wall Reconstruction.

This article provides an approach to open complex abdominal wall reconstruction. Herein, the authors discuss the purpose of component separation as well as its relevant indications. The techniques and anatomical considerations of both anterior and posterior component separation are described. In addition, patient selection criteria, preoperative adjuncts that may assist with fascial or soft tissue closure, and complications of component separation will be discussed.

Distressed community index as a predictor of presentation and postoperative outcomes in ventral hernia repair.

BACKGROUND: We evaluated the impact of socioeconomic status on presentation, management, and outcomes of ventral hernias. METHODS: The Abdominal Core Health Quality Collaborative was queried for adult patients undergoing ventral hernia repair. Socioeconomic quintiles were assigned using the Distressed Community Index (DCI): prosperous (0-20), comfortable (21-40), mid-tier (41-60), at-risk (61-80), and distressed (81-100). Outcomes included presenting symptoms, urgency, operative details, 30-day outcomes, and one-year hernia recurrence rates. Multivariable regression evaluated 30-day wound complications. RESULTS: 39,494 subjects were identified; 32,471 had zip codes (82.2%).Urgent presentation (3.6% vs. 2.3%) and contaminated cases (0.83% vs. 2.06%) were more common in the distressed group compared to the prosperous group (p < 0.001). Higher DCI correlated with readmission (distressed: 4.7% vs prosperous: 2.9%,p < 0.001) and reoperation (distressed 1.8% vs prosperous: 0.92%,p < 0.001). Wound complications were independently associated with increasing DCI (p < 0.05). Clinical recurrence rates were similar at one-year (distressed: 10.4% vs prosperous: 8.6%, p = 0.54). CONCLUSIONS: Inequity exists in presentation and perioperative outcomes for ventral hernia repair and efforts should be focused on increasing access to elective surgery and improving postoperative wound care.

Ceramide-Induced Lysosomal Biogenesis and Exocytosis in Early-Onset Preeclampsia Promotes Exosomal Release of SMPD1 Causing Endothelial Dysfunction.

Aberrant ceramide build-up in preeclampsia, a serious disorder of pregnancy, causes exuberant autophagy-mediated trophoblast cell death. The significance of ceramide accumulation for lysosomal biogenesis in preeclampsia is unknown. Here we report that lysosome formation is markedly increased in trophoblast cells of early-onset preeclamptic placentae, in particular in syncytiotrophoblasts. This is accompanied by augmented levels of transcription factor EB (TFEB). In vitro and in vivo experiments demonstrate that ceramide increases TFEB expression and nuclear translocation and induces lysosomal formation and exocytosis. Further, we show that TFEB directly regulates the expression of lysosomal sphingomyelin phosphodiesterase (L-SMPD1) that degrades sphingomyelin to ceramide. In early-onset preeclampsia, ceramide-induced lysosomal exocytosis carries L-SMPD1 to the apical membrane of the syncytial epithelium, resulting in ceramide accumulation in lipid rafts and release of active L-SMPD1 via ceramide-enriched exosomes into the maternal circulation. The SMPD1-containing exosomes promote endothelial activation and impair endothelial tubule formation in vitro. Both exosome-induced processes are attenuated by SMPD1 inhibitors. These findings suggest that ceramide-induced lysosomal biogenesis and exocytosis in preeclamptic placentae contributes to maternal endothelial dysfunction, characteristic of this pathology.

Minimally invasive approach to low-velocity penetrating extraperitoneal rectal trauma.

Unlike intraperitoneal colorectal injuries, the standard of care for extraperitoneal rectal trauma includes a diverting colostomy due to relative inaccessibility of these injuries for primary repair. New technologies to enhance access to the extraperitoneal rectum have gained increasing use in benign and malignant rectal disease. We present two cases of low-velocity penetrating extraperitoneal rectal trauma. In both cases, a transanal minimally invasive surgery (TAMIS) approach was used to access, and primarily repair, full-thickness rectal lacerations. These patients were successfully managed without a colostomy and without complication. TAMIS enables access to distal rectal injuries, facilitating primary repair and bringing the management of extraperitoneal rectal injuries in line with intraperitoneal injuries, with the potential to avoid fecal diversion.

A Single Sphingomyelin Species Promotes Exosomal Release of Endoglin into the Maternal Circulation in Preeclampsia.

Preeclampsia (PE), an hypertensive disorder of pregnancy, exhibits increased circulating levels of a short form of the auxillary TGF-beta (TGFB) receptor endoglin (sENG). Until now, its release and functionality in PE remains poorly understood. Here we show that ENG selectively interacts with sphingomyelin(SM)-18:0 which promotes its clustering with metalloproteinase 14 (MMP14) in SM-18:0 enriched lipid rafts of the apical syncytial membranes from PE placenta where ENG is cleaved by MMP14 into sENG. The SM-18:0 enriched lipid rafts also contain type 1 and 2 TGFB receptors (TGFBR1 and TGFBR2), but not soluble fms-like tyrosine kinase 1 (sFLT1), another protein secreted in excess in the circulation of women with PE. The truncated ENG is then released into the maternal circulation via SM-18:0 enriched exosomes together with TGFBR1 and 2. Such an exosomal TGFB receptor complex could be functionally active and block the vascular effects of TGFB in the circulation of PE women.

Disruption of sphingolipid metabolism augments ceramide-induced autophagy in preeclampsia.

Bioactive sphingolipids including ceramides are involved in a variety of pathophysiological processes by regulating cell death and survival. The objective of the current study was to examine ceramide metabolism in preeclampsia, a serious disorder of pregnancy characterized by oxidative stress, and increased trophoblast cell death and autophagy. Maternal circulating and placental ceramide levels quantified by tandem mass spectrometry were elevated in pregnancies complicated by preeclampsia. Placental ceramides were elevated due to greater de novo synthesis via high serine palmitoyltransferase activity and reduced lysosomal breakdown via diminished ASAH1 expression caused by TGFB3-induced E2F4 transcriptional repression. SMPD1 activity was reduced; hence, sphingomyelin degradation by SMPD1 did not contribute to elevated ceramide levels in preeclampsia. Oxidative stress triggered similar changes in ceramide levels and acid hydrolase expression in villous explants and trophoblast cells. MALDI-imaging mass spectrometry localized the ceramide increases to the trophophoblast layers and syncytial knots of placentae from pregnancies complicated by preeclampsia. ASAH1 inhibition or ceramide treatment induced autophagy in human trophoblast cells via a shift of the BOK-MCL1 rheostat toward prodeath BOK. Pharmacological inhibition of ASAH1 activity in pregnant mice resulted in increased placental ceramide content, abnormal placentation, reduced fetal growth, and increased autophagy via a similar shift in the BOK-MCL1 system. Our results reveal that oxidative stress-induced reduction of lysosomal hydrolase activities in combination with elevated de novo synthesis leads to ceramide overload, resulting in increased trophoblast cell autophagy, and typifies preeclampsia as a sphingolipid storage disorder.

Placental autophagy regulation by the BOK-MCL1 rheostat.

Autophagy is the catabolic degradation of cellular cytoplasmic constituents via the lysosomal pathway that physiologically elicits a primarily cytoprotective function, but can rapidly be upregulated in response to stressors thereby inducing cell death. We have reported that the balance between the BCL2 family proteins BOK and MCL1 regulates human trophoblast cell fate and its alteration toward cell death typifies preeclampsia. Here we demonstrate that BOK is a potent inducer of autophagy as shown by increased LC3B-II production, autophagosomal formation and lysosomal activation in HEK 293. In contrast, using JEG3 cells we showed that prosurvival MCL1 acts as a repressor of autophagy via an interaction with BECN1, which is abrogated by BOK. We found that MCL1-cleaved products, specifically MCL1c157, trigger autophagy while the splicing variant MCL1S has no effect. Treatment of JEG3 cells with nitric oxide donor SNP resulted in BOK-MCL1 rheostat dysregulation, favoring BOK accumulation, thereby inducing autophagy. Overexpression of MCL1 rescued oxidative stress-induced autophagy. Of clinical relevance, we report aberrant autophagy levels in the preeclamptic placenta due to impaired recruitment of BECN1 to MCL1. Our data provided the first evidence for a key role of the BOK-MCL1 system in regulating autophagy in the human placenta, whereby an adverse environment as seen in preeclampsia tilts the BOK-MCL1 balance toward the build-up of isoforms that triggers placental autophagy.

Where polarity meets fusion: role of Par6 in trophoblast differentiation during placental development and preeclampsia.

Trophoblast cell fusion is a prerequisite for proper human placental development. Herein we examined the contribution of Par6 (Partitioning defective protein 6), a key regulator of cell polarity, to trophoblast cell fusion in human placental development. During early placentation, Par6 localized to nuclei of cytotrophoblast cells but with advancing gestation Par6 shifted its localization to the cytoplasm and apical brush border of the syncytium. Exposure of primary isolated trophoblasts to 3% O(2) resulted in elevated Par6 expression, maintenance of tight junction marker ZO-1 at cell boundaries, and decreased fusogenic syncytin 1 expression compared with cells cultured at 20% O(2). Treatment of choriocarcinoma BeWo cells with forskolin, a known inducer of fusion, increased syncytin 1 expression but decreased that of Par6 and ZO-1. Par6 overexpression in the presence of forskolin maintained ZO-1 at cell boundaries while decreasing syncytin 1 levels. In contrast, silencing of Par6 disrupted ZO-1 localization at cell boundaries and altered the expression and distribution of acetylated α-tubulin. Par6 expression was elevated in preeclamptic placentas relative to normotensive preterm controls and Par6 located to trophoblast cells expressing ZO-1. Together, our data indicate that Par6 negatively regulates trophoblast fusion via its roles on tight junctions and cytoskeleton dynamics and provide novel insight into the contribution of this polarity marker in altered trophoblast cell fusion typical of preeclampsia.