Outcomes of light and midweight synthetic mesh use in clean-contaminated and contaminated ventral incisional hernia repair: an ACHQC comparative analysis.

BACKGROUND: Use of macroporous synthetic mesh in contaminated ventral hernia repair has become more frequent. The objective of this study is to compare the outcomes of ventral incisional hernia repair with permanent synthetic mesh in contaminated fields to those in a clean field. METHODS: The Abdominal Core Health Quality Collaborative registry, a prospectively updated longitudinal hernia-specific national database, was retrospectively queried for adults who underwent open ventral incisional hernia repair using light or medium-weight synthetic mesh and classified as clean (CDC Class I) or contaminated (CDC Class II/III). Univariate analysis was used to compare demographic information, hernia characteristics, and operative details. Odds ratios (OR) were calculated using multivariable logistic regression for the primary outcome of 30-day surgical site infection (SSI) and secondary outcomes of 30-day surgical site occurrence (SSO), SSO requiring procedural intervention (SSO-PI), and clinical recurrence at one year. RESULTS: 7219 cases met criteria for inclusion; 13.2% of these were contaminated. 83.4% of patients had follow-up data at 30 days and 20.8% at 1 year. The adjusted OR for 30-day SSI in contaminated fields compared to clean was 2.603 (95% CI 1.959-3.459). OR for 30-day SSO was 1.275 (95% CI 1.017-1.600) and 2.355 (95%CI 1.817-3.053) for 30-day SSO-PI. OR for recurrence at one year was 1.489 (95%CI 0.892-2.487). Contaminated cases had higher rates of mesh infection (3.9% vs 0.8%, p < 0.001) and mesh removal (7.3 vs 2.5%, p < 0.001) at 1 year. CONCLUSIONS: After adjusting for baseline differences, patients undergoing ventral incisional hernia repair using light or midweight synthetic mesh in contaminated fields have higher odds of 30-day SSI, SSO, and SSO-PI than those performed in clean wounds. The odds of recurrence did not statistically differ and further studies with long-term outcomes are needed to better evaluate the best treatment options for this patient population.

Evaluation of Treatment Differences Between Men and Women Undergoing Ventral Hernia Repair: An Analysis of the Abdominal Core Health Quality Collaborative.

BACKGROUND: Sex is emerging as an important clinical variable associated with surgical outcomes and decision making. However, its relevance in regard to baseline and treatment differences in primary and incisional ventral hernia repair remains unclear. STUDY DESIGN: This is a retrospective cohort study using the Abdominal Core Health Quality Collaborative database to identify elective umbilical, epigastric, or incisional hernia repairs. Propensity matching was performed to investigate confounder-adjusted treatment differences between men and women. Treatments of interest included surgical approach (minimally invasive or open), mesh use, mesh type, mesh position, anesthesia type, myofascial release, fascial closure, and fixation use. RESULTS: A total of 8,489 umbilical, 1,801 epigastric, and 16,626 incisional hernia repairs were identified. Women undergoing primary ventral hernia repair were younger (umbilical 46.4 vs 54 years, epigastric 48.7 vs 52.7 years), with lower BMI (umbilical 30.4 vs 31.5, epigastric 29.2 vs 31.1), and less likely diabetic (umbilical 9.9% vs 11.4%, epigastric 6.8% vs 8.8%). Women undergoing incisional hernia repair were also younger (mean 57.5 vs 59.1 years), but with higher BMI (33.1 vs 31.5), and more likely diabetic (21.4% vs 19.1%). Propensity-matched analysis included 3,644 umbilical, 1,232 epigastric, and 12,480 incisional hernias. Women with incisional hernia were less likely to undergo an open repair (60.2% vs 63.4%, p < 0.001) and have mesh used (93.8% vs 94.8%, p = 0.02). In umbilical and incisional hernia repairs, women had higher rates of intraperitoneal mesh placement and men had higher rates of preperitoneal and retro-muscular mesh placement. CONCLUSIONS: Small but statistically significant treatment differences in operative approach, mesh use, and mesh position exist between men and women undergoing ventral hernia repair. It remains unknown whether these treatment differences result in differing clinical outcomes.

Therapeutic MK2 inhibition blocks pathological vascular smooth muscle cell phenotype switch.

Vascular procedures, such as stenting, angioplasty, and bypass grafting, often fail due to intimal hyperplasia (IH), wherein contractile vascular smooth muscle cells (VSMCs) dedifferentiate to synthetic VSMCs, which are highly proliferative, migratory, and fibrotic. Previous studies suggest MAPK-activated protein kinase 2 (MK2) inhibition may limit VSMC proliferation and IH, although the molecular mechanism underlying the observation remains unclear. We demonstrated here that MK2 inhibition blocked the molecular program of contractile to synthetic dedifferentiation and mitigated IH development. Molecular markers of the VSMC contractile phenotype were sustained over time in culture in rat primary VSMCs treated with potent, long-lasting MK2 inhibitory peptide nanopolyplexes (MK2i-NPs), a result supported in human saphenous vein specimens cultured ex vivo. RNA-Seq of MK2i-NP-treated primary human VSMCs revealed programmatic switching toward a contractile VSMC gene expression profile, increasing expression of antiinflammatory and contractile-associated genes while lowering expression of proinflammatory, promigratory, and synthetic phenotype-associated genes. Finally, these results were confirmed using an in vivo rabbit vein graft model where brief, intraoperative treatment with MK2i-NPs decreased IH and synthetic phenotype markers while preserving contractile proteins. These results support further development of MK2i-NPs as a therapy for blocking VSMC phenotype switch and IH associated with cardiovascular procedures.

Hemodynamic Parameters in the Assessment of Fluid Status in a Porcine Hemorrhage and Resuscitation Model.

BACKGROUND: Measuring fluid status during intraoperative hemorrhage is challenging, but detection and quantification of fluid overload is far more difficult. Using a porcine model of hemorrhage and over-resuscitation, it is hypothesized that centrally obtained hemodynamic parameters will predict volume status more accurately than peripherally obtained vital signs. METHODS: Eight anesthetized female pigs were hemorrhaged at 30 ml/min to a blood loss of 400 ml. After each 100 ml of hemorrhage, vital signs (heart rate, systolic blood pressure, mean arterial pressure, diastolic blood pressure, pulse pressure, pulse pressure variation) and centrally obtained hemodynamic parameters (mean pulmonary artery pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac output) were obtained. Blood volume was restored, and the pigs were over-resuscitated with 2,500 ml of crystalloid, collecting parameters after each 500-ml bolus. Hemorrhage and resuscitation phases were analyzed separately to determine differences among parameters over the range of volume. Conformity of parameters during hemorrhage or over-resuscitation was assessed. RESULTS: During the course of hemorrhage, changes from baseline euvolemia were observed in vital signs (systolic blood pressure, diastolic blood pressure, and mean arterial pressure) after 100 ml of blood loss. Central hemodynamic parameters (mean pulmonary artery pressure and pulmonary capillary wedge pressure) were changed after 200 ml of blood loss, and central venous pressure after 300 ml of blood loss. During the course of resuscitative volume overload, changes were observed from baseline euvolemia in mean pulmonary artery pressure and central venous pressure after 500-ml resuscitation, in pulmonary capillary wedge pressure after 1,000-ml resuscitation, and cardiac output after 2,500-ml resuscitation. In contrast to hemorrhage, vital sign parameters did not change during over-resuscitation. The strongest linear correlation was observed with pulmonary capillary wedge pressure in both hemorrhage (r2 = 0.99) and volume overload (r2 = 0.98). CONCLUSIONS: Pulmonary capillary wedge pressure is the most accurate parameter to track both hemorrhage and over-resuscitation, demonstrating the unmet clinical need for a less invasive pulmonary capillary wedge pressure equivalent.

Non-Invasive Venous waveform Analysis (NIVA) for volume assessment during complex cranial vault reconstruction: A proof-of-concept study in children.

BACKGROUND: Non-Invasive Venous waveform Analysis (NIVA) is novel technology that captures and analyzes changes in venous waveforms from a piezoelectric sensor on the wrist for hemodynamic volume assessment. Complex cranial vault reconstruction is performed in children with craniosynostosis and is associated with extensive blood loss, potential life-threatening risks, and significant morbidity. In this preliminary study, we hypothesized that NIVA will provide a reliable, non-invasive, quantitative assessment of intravascular volume changes in children undergoing complex cranial vault reconstruction. OBJECTIVE: To present proof-of-concept results of a novel technology in the pediatric population. METHODS: The NIVA prototype was placed on each subject's wrist, and venous waveforms were collected intraoperatively. Estimated blood loss and fluid/blood product administration were recorded in real time. Venous waveforms were analyzed into a NIVA value and then correlated, along with mean arterial pressure (MAP), to volume changes. Concordance was quantified to determine if the direction of change in volume was similar to the direction of change in MAP or change in NIVA. RESULTS: Of 18 patients enrolled, 14 had usable venous waveforms, and there was a significant correlation between change in NIVA value and change in volume. Change in MAP did not correlate with change in volume. The concordance between change in MAP and change in volume was less than the concordance between change in NIVA and change in volume. CONCLUSION: NIVA values correlate more closely to intravascular volume changes in pediatric craniofacial patients than MAP. This initial study suggests that NIVA is a potential safe, reliable, non-invasive quantitative method of measuring intravascular volume changes for children undergoing surgery.

The Role of Vitamin A in Wound Healing.

Vitamin A is an essential micronutrient that comes in multiple forms, including retinols, retinals, and retinoic acids. Dietary vitamin A is absorbed as retinol from preformed retinoids or as pro-vitamin A carotenoids that are converted into retinol in the enterocyte. These are then delivered to the liver for storage via chylomicrons and later released into the circulation and to its biologically active tissues bound to retinol-binding protein. Vitamin A is a crucial component of many important and diverse biological functions, including reproduction, embryological development, cellular differentiation, growth, immunity, and vision. Vitamin A functions mostly through nuclear retinoic acid receptors, retinoid X receptors, and peroxisome proliferator-activated receptors. Retinoids regulate the growth and differentiation of many cell types within skin, and its deficiency leads to abnormal epithelial keratinization. In wounded tissue, vitamin A stimulates epidermal turnover, increases the rate of re-epithelialization, and restores epithelial structure. Retinoids have the unique ability to reverse the inhibitory effects of anti-inflammatory steroids on wound healing. In addition to its role in the inflammatory phase of wound healing, retinoic acid has been demonstrated to enhance production of extracellular matrix components such as collagen type I and fibronectin, increase proliferation of keratinocytes and fibroblasts, and decrease levels of degrading matrix metalloproteinases.

The Impact of an Interventional Pulmonary Program on Nontherapeutic Lung Resections.

BACKGROUND: Pulmonary resection can concurrently diagnose and treat known or suspected lung cancer, but is not without risk. Benign resection rates range widely (9% to 40%). We evaluated the impact of an Interventional Pulmonology (IP) program and dedicated Pulmonary Nodule Clinic on surgical benign resection rates at a single institution. METHODS: An IP program was initiated in August 2010 that offered advanced diagnostic techniques and a dedicated Pulmonary Nodule Clinic was opened in August 2013. We retrospectively reviewed all patients who underwent resection for known or suspected lung cancer between 2005 and 2015 at our tertiary referral hospital. Demographics, preoperative tissue diagnoses, surgical procedure, final pathology, and staging were collected. Quarterly benign resection rates were calculated and plotted on a statistical quality control chart (P-Chart) to determine the impact of the IP program and Pulmonary Nodule Clinic on benign resection rates over time. RESULTS: Of 1112 resections, 209 (19%) were benign. Variation in quarterly benign resection rates decreased after introduction of the IP program in 2010, and a significant (P<0.05) sustained decrease in the quarterly benign resection rate occurred after introduction of the pulmonary nodule clinic in 2013 to a new baseline of 12% compared with 24% before 2010. After introduction of the IP program, mean quarterly preoperative tissue diagnostic rates increased from 45% to 58% (P<0.01). CONCLUSION: Integration of an IP program employing advanced diagnostic bronchoscopic techniques has improved preoperative diagnostic rates of suspicious pulmonary nodules and in combination with a pulmonary nodule clinic has resulted in fewer benign resections.

Increased IL-6 detection in adult and pediatric lymphoid tissue harboring parvovirus B19.

BACKGROUND: Parvovirus B19 (B19V) is a common pathogenic virus infecting humans. Previous studies have shown evidence of B19V infection in patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma using ELISA and PCR on serum specimens. B19V nonstructural protein is known to alter the expression of cellular factors including interleukin-6 (IL-6), which can increase the risk for and worsen the prognosis of lymphomas. OBJECTIVE: The objective of this study was to detect B19V capsid protein and IL-6 expression in normal and malignant lymphoid tissue, as well as any correlation between the two. STUDY DESIGN: IHCs for B19V capsid protein, IL-6, and B19V co-receptors P-antigen and α5ß1 integrin were performed on a tissue array containing 70 duplicated pediatric and adult lymphoma tissues and 5 duplicated benign lymph node sections. Cases were identified as normal, B-cell NHL, diffuse large B-cell NHL, Hodgkin's lymphoma, extranodal NK/T cell lymphoma, anaplastic large cell lymphoma, or mantle cell lymphoma. IL-6 and B19V capsid staining were quantified using a positive pixel count algorithm, and P-antigen and α5ß1 staining using a membrane quantification algorithm. RESULTS: B19V capsid protein was detected in both benign and malignant lymphoid tissue. The Spearman rank correlation coefficient analysis was performed to determine the relationship between the level of positivity for B19V and IL-6 staining, yielding an overall correlation coefficient of 0.679 (p-value<0.0001). CONCLUSIONS: Our results show a moderate correlation between the levels of positive B19V and IL-6 staining by IHC, indicating a possible role for B19V in the pathogenesis of lymphomas.

Detection of parvovirus B19 capsid proteins in testicular tissues.

OBJECTIVE: To detect B19 capsid proteins, VP1 and VP2, in testicular tissues, both normal and tumor, using immunohistochemistry. METHODS: Samples of normal, fetal, and tumor testicular tissue (n = 31) and normal testicular DNA (n = 1) were tested for the presence of B19. Immunohistochemistry staining was used for the detection of viral capsid proteins VP1 and VP2. Polymerase chain reaction with 4 primer sets was used to test for the presence of B19 DNA in a normal testicular sample. RESULTS: B19 capsid protein VP1 and VP2 was detected by immunohistochemistry in 6 (85.7%) of 7 normal testicular samples and 17 (73.9%) of 23 tumor samples. The findings from a normal fetal testicular sample were equivocal. B19 DNA was detected in normal testicular DNA with 4 of the 4 primer sets used. CONCLUSION: In contrast to previous reports, B19 capsid proteins VP1 and VP2 have now been detected in both normal and tumor testicular tissue. The persistence of B19 in a diverse range of tissues, including the testes, requires more research into the molecular mechanisms by which B19 can enter these cells, as well as the possible etiologic roles in chronic diseases, including cancer.