Outcomes of a new slowly resorbable biosynthetic mesh (Phasix™) in potentially contaminated incisional hernias: A prospective, multi-center, single-arm trial.

BACKGROUND: Resorbable biomaterials have been developed to reduce the amount of foreign material remaining in the body after hernia repair over the long-term. However, on the short-term, these resorbable materials should render acceptable results with regard to complications, infections, and reoperations to be considered for repair. Additionally, the rate of resorption should not be any faster than collagen deposition and maturation; leading to early hernia recurrence. Therefore, the objective of this study was to collect data on the short-term performance of a new resorbable biosynthetic mesh (Phasix™) in patients requiring Ventral Hernia Working Group (VHWG) Grade 3 midline incisional hernia repair. MATERIALS AND METHODS: A prospective, multi-center, single-arm trial was conducted at surgical departments in 15 hospitals across Europe. Patients aged ≥18, scheduled to undergo elective Ventral Hernia Working Group Grade 3 hernia repair of a hernia larger than 10 cm2 were included. Hernia repair was performed with Phasix™ Mesh in sublay position when achievable. The primary outcome was the rate of surgical site occurrence (SSO), including infections, that required intervention until 3 months after repair. RESULTS: In total, 84 patients were treated with Phasix™ Mesh. Twenty-two patients (26.2%) developed 32 surgical site occurrences. These included 11 surgical site infections, 9 wound dehiscences, 7 seromas, 2 hematomas, 2 skin necroses, and 1 fistula. No significant differences in surgical site occurrence development were found between groups repaired with or without component separation technique, and between clean-contaminated or contaminated wound sites. At three months, there were no hernia recurrences. CONCLUSION: Phasix™ Mesh demonstrated acceptable postoperative surgical site occurrence rates in patients with a Ventral Hernia Working Group Grade 3 hernia. Longer follow-up is needed to evaluate the recurrence rate and the effects on quality of life. This study is ongoing through 24 months of follow-up.

Oral Administration of 99mTechnetium-Labeled Heparin in Eosinophilic Esophagitis.

OBJECTIVE: To determine if heparin labeled with 99mTechnetium (99mTc) could be an imaging probe to detect eosinophil-related inflammation in eosinophilic esophagitis and to determine the biodistribution and radiation dosimetry of 99mTc-heparin oral administration using image-based dosimetry models with esophageal modeling. METHODS: Freshly prepared 99mTc-heparin was administered orally to 5 research subjects. Radioactivity was measured by whole-body scintigraphy and single-photon emission computed tomography during the 24 hours postadministration. Following imaging, endoscopic examination was performed. The biodistribution of esophageal radioactivity was compared with endoscopic findings, eosinophil counts in biopsy tissues, and immunostaining for eosinophil granule major basic protein-1 (eMBP1). These studies were conducted from July 1, 2013, until April 22, 2017. RESULTS: Oral administration of 99mTc-heparin was well tolerated in all 5 subjects. The entire esophagus could be visualized dynamically during oral administration. Bound esophageal radioactivity marked areas of inflammation as judged by endoscopy scores, by eosinophils per high power field and by localization of eMBP1 using immunostaining. Ninety percent of the radioactivity did not bind to the esophagus and passed through the gastrointestinal tract. CONCLUSION: The biodistribution of ingested 99mTc-heparin is almost exclusively localized to the gastrointestinal tract. Radiation exposure was highest in the lower gastrointestinal tract and was comparable with other orally administered diagnostic radiopharmaceuticals. The use of swallowed 99mTc-heparin may aid in assessing eosinophil-related inflammation in the esophagus.

Immunotherapeutics for head and neck squamous cell carcinoma stem cells.

Cancer stem cell (CSC)-related therapy resistance has become a new obstacle to the successful application of cancer treatment and head and neck squamous cell carcinoma (HNSCC) is no exception to this finding. Head and neck squamous cell carcinoma is highly immune-suppressive, and recently the immune suppression and invasion of HNSCC-CSCs have been characterized. These characteristics have received research and clinical attention because they would enable the stratification of patients into specific cancer subtypes and, consequently, the establishment of new therapeutic approaches with improved efficacy. This review discusses the feasibility of CSC-targeted strategies and their incorporation with nanotechnology to improve the efficacy of cancer immunotherapy.

Zinc-Impregnated Mesh for Abdominal Wall Repair Reduces Infection in a Rat Model of Peritonitis.

BACKGROUND: The objective of this study was to assess whether a zinc-impregnated polypropylene mesh (ZnMesh) has better antibacterial properties in a contaminated environment compared with a regular polypropylene mesh. MATERIALS AND METHODS: Thirty-eight Wistar Han rats underwent cecal ligation and puncture to induce peritonitis 24 h before implantation of an intraperitoneal ZnMesh or a regular polypropylene mesh. Primary outcome was the number of colony forming units (CFU) per sample (mesh and abdominal wall). Secondary outcomes were macroscopic (incorporation of mesh, abscesses, and adhesions on mesh surface) and histological (inflammatory cell reaction, mesh-specific parameters, and collagen deposition) parameters. All outcomes were evaluated after 30 and 90 d. RESULTS: After 30 d, no significant difference in CFU per sample was present between the ZnMesh and control groups. After 90 d, a lower number of CFU per sample was present in the ZnMesh group compared with the control group (trypticase soy agar with 5% sheep blood: 0 log10 CFU/sample IQR: 0-1.40 versus 1.58 log10 CFU/sample IQR: 0-4.30, P = 0.012; MacConkey: 0 log10 CFU/sample IQR: 0-2.65 versus 1.18 log10 CFU/sample IQR: 0-4.04, P = 0.438). After 90 d, the percentage of adhesions on mesh surface was significantly higher in the ZnMesh group (95% IQR: 60%-100% versus 50% IQR: 23%-75%, P = 0.029). No differences were seen in other macroscopic outcomes or histology. CONCLUSIONS: A significantly lower number of CFU per sample was found in the ZnMesh group after 90 d. After 30 d, no statistically significant differences in CFU per sample were seen. This result suggests that the ZnMesh group has better antibacterial properties in a contaminated environment. However, this is at the cost of a significantly higher percentage of adhesions.

Risk Factors for Incarceration in Patients with Primary Abdominal Wall and Incisional Hernias: A Prospective Study in 4472 Patients.

BACKGROUND: Incarceration of primary and incisional hernias often results in emergency surgery. The objective of this study was to evaluate the relation of defect size and location with incarceration. Secondary objectives comprised identification of additional patient factors associated with an incarcerated hernia. METHODS: A registry-based prospective study was performed of all consecutive patients undergoing hernia surgery between September 2011 and February 2016. Multivariate logistic regression was performed to identify risk factors for incarceration. RESULTS: In total, 83 (3.5%) of 2352 primary hernias and 79 (3.7%) of 2120 incisional hernias had a non-reducible incarceration. For primary hernias, a defect width of 3-4 cm compared to defects of 0-1 cm was significantly associated with an incarcerated hernia (OR 2.85, 95% CI 1.57-5.18, p = 0.0006). For incisional hernias, a defect width of 3-4 cm compared to defects of 0-2 cm was significantly associated with an incarceration (OR 2.14, 95% CI 1.07-4.31, p = 0.0324). For primary hernias, defects in the peri- and infra-umbilical region portrayed a significantly increased odds for incarceration as compared to supra-umbilical defects (OR 1.98, 95% CI 1.02-3.85, p = 0.043). Additionally, in primary hernias age, BMI, and constipation were associated with incarceration. In incisional hernias age, BMI, female sex, diabetes mellitus and ASA classification were associated with incarceration. CONCLUSION: For primary and incisional hernias, mainly defects of 3-4 cm were associated with incarceration. For primary hernias, mainly defects located in the peri- and infra-umbilical region were associated with incarceration. Based on patient and hernia characteristics, patients with increased odds for incarceration may be selected and these patients may benefit from elective surgical treatment.

Anatomical study comparing medialization after Rives-Stoppa, anterior component separation, and posterior component separation.

BACKGROUND: Large incisional hernias require medialization of the rectus abdominis muscles to facilitate tension-free closure. Medialization may be achieved by Rives-Stoppa, anterior component separation, or posterior component separation. This study aims to compare medialization achieved by these techniques in postmortem human specimens. METHODS: First, the Rives-Stoppa procedure was performed. Subsequently, anterior and posterior component separation were performed on one side in each specimen, with each specimen functioning as its own control. Medialization was measured at three levels of the linea alba with three 1-kg weights. Both medialization obtained in addition to initial medialization after opening the linea alba and total medialization were measured. Results are presented as median and interquartile range. RESULTS: A total of 13 postmortem human specimens were included (Rives-Stoppa n = 13, component separation n = 10). Additional medialization after Rives-Stoppa was 1.2 cm (IQR: 0.3-2.2) for the anterior rectus sheath and 2.2 cm (IQR: 1.6-3.0) for the posterior rectus sheath (total medialization: 3.9 and 4.5 cm). For the anterior rectus sheath, additional medialization was 2.6 cm (IQR: 1.2-3.6) after anterior component separation and 1.9 cm (IQR: 0.4-3.4) after posterior component separation (P = .125, total medialization: 6.5 and 5.7 cm). For the posterior rectus sheath, additional medialization was 3.0 cm (IQR: 2.2-3.7) after anterior component separation and 5.2 cm (IQR: 4.2-5.9) after posterior component separation (P < .001, total medialization: 5.8 and 9.4 cm). CONCLUSION: Posterior component separation yielded significantly more medialization of the posterior rectus sheath compared with Rives-Stoppa and anterior component separation. Anterior component separation may provide marginally more medialization of the anterior rectus sheath.

Suppression of SIRT1 in Diabetic Conditions Induces Osteogenic Differentiation of Human Vascular Smooth Muscle Cells via RUNX2 Signalling.

Vascular calcification is associated with significant morbidity and mortality within diabetes, involving activation of osteogenic regulators and transcription factors. Recent evidence demonstrates the beneficial role of Sirtuin 1 (SIRT1), an NAD+ dependant deacetylase, in improved insulin sensitivity and glucose homeostasis, linking hyperglycaemia and SIRT1 downregulation. This study aimed to determine the role of SIRT1 in vascular smooth muscle cell (vSMC) calcification within the diabetic environment. An 80% reduction in SIRT1 levels was observed in patients with diabetes, both in serum and the arterial smooth muscle layer, whilst both RUNX2 and Osteocalcin levels were elevated. Human vSMCs exposed to hyperglycaemic conditions in vitro demonstrated enhanced calcification, which was positively associated with the induction of cellular senescence, verified by senescence-associated ß-galactosidase activity and cell cycle markers p16 and p21. Activation of SIRT1 by SRT1720 reduced Alizarin red staining by a third, via inhibition of the RUNX2 pathway and prevention of senescence. Conversely, inhibition of SIRT1 via Sirtinol and siRNA increased RUNX2 by over 50%. These findings demonstrate the key role that SIRT1 plays in preventing calcification in a diabetic environment, through the inhibition of RUNX2 and senescence pathways, suggesting a downregulation of SIRT1 may be responsible for perpetuating vascular calcification in diabetes.

[Evolution of clinical practices in the surgical management of pelvic organ prolapse in a "vaginalist" team over the period 2010-2015: A paradigm shift towards pluripotency]. / Évolution des pratiques dans la chirurgie du prolapsus au sein d'une école vaginaliste sur la période 2010­2015.

OBJECTIVES: To determine whether the 2011 FDA alert and French Guidelines have impacted the routine surgical practice in the management of pelvic organ prolapse in a "vaginalist" team over the period 2010-2015. METHODS: Retrospective study involving all patients undergoing surgical management of anterior and/or apical symptomatic pelvic organ prolapse during the civil years 2010 and 2015. Both naive and relapsed prolapses were eligible. RESULTS: Overall, 338 patients were included: 187 in 2010 and 151 in 2015. Among patients with naive prolapse, we observed a significant increase in the number of laparoscopic sacrocolpopexies (11.1% in 2010 versus 34.4% in 2015, P=0.001) and a significant decline in the use of native tissue repair (67.6% in 2010 versus 39% in 2015, P=0.001). While the number of transvaginal meshes did not decline over the study period, their indications displayed a significant evolution towards a restricted use to advanced stages. We did not observe any difference regarding the treatment of recurred pelvic organ prolapse. Vaginal route remained the preferred approach in this indication. CONCLUSION: In our "vaginalist" team, routine practice has significantly evolved over the period 2010-2015, resulting in a diversification of the healthcare offer. This paradigm shift towards pluripotency is mandatory, since patients' preference should also drive the choice of both surgical route and technique.

William Bradley Coley, MD, and the phenomenon of spontaneous regression.

The standard definition of spontaneous regression (SR) of cancer is as follows, "…when a malignant tumor partially or completely disappears without treatment or in the presence of therapy which is considered inadequate to exert a significant influence on neoplastic disease." SR is also known as Saint Peregrine tumor, the name taken from a young priest, Peregrine Laziosi (1260 [5]-1345, exact date is unknown), who had been diagnosed with a tumor of the tibia. The mass eventually grew so large that it broke through the skin and became severely infected. The available treatment for this condition was limited to amputation. Historical records report that on the day of surgery, physicians found that the tumor had disappeared and reportedly never returned. To date, the medical literature consists only of individual case studies and overviews of this phenomenon. The most cited work on the subject was done by surgeons Tilden Everson and Warren Cole who reviewed 176 published cases of SR from 1900 to 1960. While a percentage of these were found not to be cases of SR, there remained a number of unexplained cases. A frequent theme in many cases of SR is the co-occurrence of infection. Given the current interest in immunotherapy in the treatment of cancer, this article discusses one of the very early pioneers of this theory, William Bradley Coley, MD, a surgeon who was clearly ahead of his time. Ostracized by colleagues for his belief that stimulation of the immune system could in fact produce a regression of cancer, Coley remained convinced that his theory was right and, while he was not familiar with cytokines such as tumor necrosis factor (TNF), interferons, and streptokinase, he knew instinctively that an innate immune response was taking place.

Direct monitoring of spin transitions in a dinuclear triple-stranded helicate iron(ii) complex through X-ray photoelectron spectroscopy.

A dinuclear helical iron(ii) complex of a new ditopic thiazolylimine ligand (L) has been synthesised via supramolecular assembly. The resulting dinuclear helical cylinder [Fe2L3]·4BF4 was investigated by variable temperature X-ray crystallography, ESI high resolution mass spectrometry, CHN analysis, FT-IR and UV-Vis spectroscopy. The nature of the spin transition was investigated by magnetic susceptibility measurements, and confirmed by VT-SCXRD and X-ray photoelectron spectroscopy. [Fe2L3]·4BF4 displays a complete spin transition with a gradual-abrupt character at T1/2 = 348 K and represents a new example of a dinuclear iron(ii) complex exhibiting a spin transition at high temperature. Both VT-SCXRD and XPS measurements show excellent correlation with the magnetic susceptibility experiments, demonstrating the power of XPS not just to confirm, but also to clearly follow the spin-state transition in Fe(ii) SCO complexes.

Primary and incisional ventral hernias are different in terms of patient characteristics and postoperative complications - A prospective cohort study of 4,565 patients.

BACKGROUND: Primary and incisional hernias are often pooled in publications studying hernia symptoms, treatment, or surgical outcomes. The question rises whether this is justified or if primary and incisional hernia should be considered as two separate entities. The aim of this prospective cohort study is to compare primary and incisional ventral hernias regarding patient characteristics, hernia characteristics, surgical characteristics, and postoperative complications. MATERIALS AND METHODS: A registry-based, prospective cohort study was performed. All patients undergoing primary or incisional hernia repair surgery between September 1st, 2011 and February 29th, 2016 were included. Patient baseline characteristics, hernia characteristics, surgical characteristics, and postoperative outcomes were collected and analyzed. RESULTS: A total of 4565 patients were included, of whom 2374 had a primary hernia and 2191 had an incisional hernia. All patient, hernia, and surgical characteristics were statistically significantly different between primary and incisional hernias except for corticosteroid use, history of inguinal hernia, incarceration, and emergency surgery. Overall complication rates (wound, surgical, and medical) were significantly different (105/2374 (4.4%) for primary hernia versus 323/2191 (15%) for incisional hernia, p < 0.001). CONCLUSION: Primary and incisional hernia are statistically significantly different for almost all patient, hernia, surgical, and postoperative characteristics analyzed. Given these differences, data on primary hernias and incisional hernias should not be pooled in studies reporting on hernia repair.

[Laparoscopic sacrocolpopexy for exteriorized pelvic organ prolapse: Mid-term functional results]. / Promontofixation cœlioscopique pour les prolapsus extériorisés: qualité de vie et résultats fonctionnels à moyen terme.

OBJECTIVES: To assess feasibility and postoperative outcomes associated with laparoscopic sacrocolpopexy in patients presenting with exteriorized pelvic organ prolapse (stage>3). METHODS: Prospective study involving patients undergoing laparoscopic sacrocolpopexy for advanced stage pelvic organ prolapse. Symptoms and quality of life were evaluated at baseline and at 1, 4 and 18 months after surgery using validated questionnaires (PFDI-20 and PFIQ-7). RESULTS: Sixty-three patients were included between September 2012 and January 2014. Sub-total hysterectomy and sub-urethral sling were performed at the time of surgery in 36% and 34% of patients, respectively. We observed 1 per-operative complication (bladder wound). De novo stress urinary incontinence and de novo dyspareunia persisting at 18 months occurred in 10% and 3% of cases, respectively. Recurrence rate was 1.6% at 18 months. The follow-up also revealed a significant and prolonged improvement in PFDI-20 and PFIQ-7 scores: from 98.8 at baseline to 33.9 at 18 months (P<0.01) and from 89.6 to 26.5 (P<0.001), respectively. CONCLUSION: Laparoscopic sacrocolpopexy seems feasible and safe in patients suffering from exteriorized pelvic organ prolapse, leading to high anatomic success rate. It is also associated with a prolonged improvement in quality of life and a positive impact on symptoms related to prolapse.

External Validation of the European Hernia Society Classification for Postoperative Complications after Incisional Hernia Repair: A Cohort Study of 2,191 Patients.

BACKGROUND: Incisional hernia is a frequent complication after midline laparotomy. Surgical hernia repair is associated with complications, but no clear predictive risk factors have been identified. The European Hernia Society (EHS) classification offers a structured framework to describe hernias and to analyze postoperative complications. Because of its structured nature, it might prove to be useful for preoperative patient or treatment classification. The objective of this study was to investigate the EHS classification as a predictor for postoperative complications after incisional hernia surgery. STUDY DESIGN: An analysis was performed using a registry-based, large-scale, prospective cohort study, including all patients undergoing incisional hernia surgery between September 1, 2011 and February 29, 2016. Univariate analyses and multivariable logistic regression analysis were performed to identify risk factors for postoperative complications. RESULTS: A total of 2,191 patients were included, of whom 323 (15%) had 1 or more complications. Factors associated with complications in univariate analyses (p < 0.20) and clinically relevant factors were included in the multivariable analysis. In the multivariable analysis, EHS width class, incarceration, open surgery, duration of surgery, Altemeier wound class, and therapeutic antibiotic treatment were independent risk factors for postoperative complications. Third recurrence and emergency surgery were associated with fewer complications. CONCLUSIONS: Incisional hernia repair is associated with a 15% complication rate. The EHS width classification is associated with postoperative complications. To identify patients at risk for complications, the EHS classification is useful.

Oxygen therapies and their effects on wound healing.

Oxygen is an important factor for wound healing. Although several different therapies investigated the use of oxygen to aid wound healing, the results of these studies are not unequivocal. This systematic review summarizes the clinical and experimental studies regarding different oxygen therapies for promoting wound healing, and evaluates the outcomes according the methodological details. A systematic literature search was conducted using Embase, Medline, Web of Science, Cochrane, PubMed publisher, and Google Scholar libraries. Clinical and experimental studies investigating oxygen for wound healing were selected. Included articles were categorized according to the kind of therapy, study design, and wound type. The methodological details were extracted and analyzed. Sixty-five articles were identified and divided in three different oxygen therapies: Local oxygen therapy, hyperbaric oxygen therapy, and supplemental inspired oxygen therapy. More than half of the included local oxygen and hyperbaric oxygen studies had one or more significant positive outcomes, 77 and 63%, respectively. Supplemental inspired oxygen therapy during gastrointestinal and vascular surgery was more likely to have a positive result than during other surgical interventions reducing surgical site infections. These many positive outcomes promote the use of oxygen treatment in the stimulation of wound healing. However, the lack of clinical studies and vast methodological diversity made it impossible to perform a proper comparison within and between the different therapies. Further randomized clinical studies are warranted to examine the value of these therapies, especially studies that investigate the more patient-friendly oxygen dressings and topical wound oxygen therapies. Also, to achieve more solid and consistent data, studies should use more standardized methods and subjects.

Long term results of open complex abdominal wall hernia repair with self-gripping mesh: A retrospective cohort study.

BACKGROUND: In case of complex ventral hernias, Rives-Stoppa and component separation technique are considered as favourable treatment techniques. However, mesh-related complications like recurrence, infection and chronic pain are still a common problem after mesh repair. Previous studies have reported promising results of the use of a self-gripping mesh (ProGrip™) in incisional hernia repair. This study aimed to evaluate the long term results of this mesh for complex ventral hernia treatment. MATERIALS AND METHODS: Patients with complex ventral hernia undergoing repair between June 2012 and June 2015, using the ProGrip™-mesh in retromuscular position, were included. All patients visited the outpatient clinic to evaluate short term complications and recurrence. After at least one year, telephone interviews were conducted to evaluate long term results. RESULTS: A total of 46 patients (median age 59 years) were included. 40 patients (87%) were diagnosed with incisional hernia. Seven patients (18%) had incisional hernia combined with another hernia. Four patients (8.7%) had an umbilical hernia, one patient (2.2%) had an epigastric hernia and one patient (2.2%) had rectus diastasis. 39 patients completed follow-up. Median follow-up was 25 months (IQR: 19-35 months). 28 patients (72%) did not report any complaints. Nine patients reported pain (average VAS of 1.7). Two patients developed a recurrence requiring reoperation. One patient developed mesh infection requiring reoperation. CONCLUSION: Long term results of the use of a self-gripping mesh for complex abdominal wall hernias show a low recurrence rate, even in complex hernia cases. This makes the mesh a good choice in this difficult patient group.

Syntheses, structures and magnetic properties of tetranuclear cubane-type and heptanuclear wheel-type nickel(ii) complexes with 3-methoxysalicylic acid derivatives.

Two ferromagnetic multinuclear Ni(ii) clusters, [Ni4L14(µ3-OMe)4(CH3OH)4] (1) and [Ni7(HL2)6(µ3-OMe)6]Cl2 (2), and a mononuclear complex [NiL3]·2H2O (3) (HL1 = benzyl 2-hydroxy-3-methoxybenzoate; H2L2 = 1-(2-hydroxy-3-methoxybenzamido)-2-(benzylideneamino)ethane; H2L3 = 1-(2-hydroxy-3-methoxybenzamido)-2-(pyridylmethyleneamino)ethane) were synthesised, and their structures and magnetic behaviours were investigated in detail. 1 has a [Ni4O4] cubane structure while 2 has a wheel-like [Ni@Ni6] arrangement. The temperature-dependent magnetic susceptibilities for 1 and 2 are in accord with the presence of dominating intra-cluster ferromagnetic interactions between Ni(ii) ions. The best fits for their behaviours gave the following parameters: J1 = 11.06 cm-1, J2 = 1.43 cm-1, g = 2.29 for 1, and J1 = 6.87 cm-1, J2 = -3.41 cm-1, g = 2.24 for 2.

Sutureless closure of colonic defects with tissue adhesives: an in vivo study in the rat.

BACKGROUND: Tissue adhesives (TAs) in gastrointestinal surgery are gradually gaining acceptance. Before implementation as colonic sealants, an evaluation of the sealing capability of a TA when in contact with fecal matter, as in a leaking anastomosis, is needed. In this study, we used clinically available TAs for the sutureless closure of colonic defects evaluating mechanical strength and tissue healing. METHODS: A total of 160 rats were divided into 8 groups. Two .5-cm incisions were created, one in the proximal and another in the distal colon. Incisions were sealed with a TA: Histoacryl Flex, Bioglue, Dermabond, Tissucol, Duraseal Xact, gelatin-resorcinol-formaldehyde or Glubran 2. A control group was included in which the colonic defects were not sealed. Follow-up time was 3 or 10 days. Clinical complication rate, bursting pressure, and histopathologic analysis was included. RESULTS: Leakage rates in the TA groups were highest for Duraseal Xact, Bioglue, and gelatin-resorcinol-formaldehyde at 3 and 10 days. The cyanoacrylates Glubran 2, Histoacryl Flex, and Omnex, and the fibrin glue Tissucol showed the lowest overall clinical complication rates while maintaining the highest bursting pressure at day 10. Histoacryl Flex exhibited significantly higher collagen formation at day 10 than the other TAs. CONCLUSIONS: This experimental model evaluates the protective effect of a TA seal on a leaking colonic defect. We found large differences in leakage rates and inertness of the tested TAs. The cyanoacrylates Histoacryl Flex, Omnex, and Glubran 2 as well as the fibrin glue Tissucol demonstrated the lowest leakage rates and the most inert histopathologic profile while maintaining high mechanical strength.

Spin-State Patterning in an Iron(II) Tripodal Spin-Crossover Complex.

A mononuclear iron(II) complex that displays a gradual two-step spin-crossover (SCO) transition is reported. The intermediate plateau (IP) occurs between HS0.40LS0.60 and HS0.30LS0.70 (HS = high spin; LS = low spin) ratios over the region of ca. 190-170 K. A phase change occurs at the IP, breaking the symmetry, resulting in six independent SCO sites compared to one at the 100% HS and LS plateau regions, respectively. Variable-temperature X-ray photoelectron spectroscopy shows that the SCO behavior is completely reversible among the HS, IP, and LS regions. The results both confirm and extend the related results for the above system described by Halcrow et al. (Kulmaczewski R.; Cespedes O.; Halcrow M. A.Gradual Thermal Spin-Crossover Mediated By a Reentrant Z' = 1 → Z' = 6 → Z' = 1 Phase Transition, Inorg. Chem. 2017, 56, 3144-3148) in a recent report.

Clinical, mechanical, and immunohistopathological effects of tissue adhesives on the colon: An in-vivo study.

BACKGROUND: Tissue adhesives may be useful for sealing bowel anastomoses by preventing anastomotic leakage. Prior to clinical implementation, an in-depth analysis of the clinical and immunohistopathological effects of tissue adhesives on the target tissue and of the mechanical strength of the adhesive bond in an in vivo model is needed. MATERIALS AND METHODS: In 84 rats, two bowel segments were glued using one of the following tissue adhesive: Bioglue, Gelatin-resorcinol-formaldehyde (GRF), Glubran 2, Histoacryl Flex, Omnex, Duraseal Xact, or Tissucol. Rats were followed for 7 or 28 days. Endpoints were clinical complication rate, mechanical strength, and immunohistopathological reactions. RESULTS: Of the seven tissue adhesives, GRF and Bioglue showed the highest rates of bowel wall destruction and ileus and the most severe immunohistopathological tissue reactions at 7 and 28 days. Cyanoacrylates (Histoacryl Flex, Omnex, Glubran 2) showed high mechanical strength and mild immunohistopathological reactions at 7 and 28 days. Duraseal Xact and Tissucol were the most inert tissue adhesives, but exhibited low mechanical strength. At 28 days, mechanical strength was significantly correlated to CD8, CD68, and Ki67 cell counts. CONCLUSION: Based on the clinical and immunohistopathological outcomes, GRF and Bioglue were found to be the least suitable tissue adhesives for colonic use. Duraseal Xact and Tissucol were inert but also showed low mechanical strength. Cyanoacrylates exhibited mild clinical and immunohistopathological effects while maintaining high strength, which makes them promising as colonic sealants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 846-854, 2017.

The phosphorylated form of FTY720 activates PP2A, represses inflammation and is devoid of S1P agonism in A549 lung epithelial cells.

Protein phosphatase 2A (PP2A) activity can be enhanced pharmacologically by PP2A-activating drugs (PADs). The sphingosine analog FTY720 is the best known PAD and we have shown that FTY720 represses production of pro-inflammatory cytokines responsible for respiratory disease pathogenesis. Whether its phosphorylated form, FTY720-P, also enhances PP2A activity independently of the sphingosine 1-phosphate (S1P) pathway was unknown. Herein, we show that FTY720-P enhances TNF-induced PP2A phosphatase activity and significantly represses TNF-induced interleukin 6 (IL-6) and IL-8 mRNA expression and protein secretion from A549 lung epithelial cells. Comparing FTY720 and FTY720-P with S1P, we show that unlike S1P, the sphingosine analogs do not induce cytokine production on their own. In fact, FTY720 and FTY720-P significantly repress S1P-induced IL-6 and IL-8 production. We then examined their impact on expression of cyclooxygenase 2 (COX-2) and resultant prostaglandin E2 (PGE2) production. S1P did not increase production of this pro-inflammatory enzyme because COX-2 mRNA gene expression is NF-κB-dependent, and unlike TNF, S1P did not activate NF-κB. However, TNF-induced COX-2 mRNA expression and PGE2 secretion is repressed by FTY720 and FTY720-P. Hence, FTY720-P enhances PP2A activity and that PADs can repress production of pro-inflammatory cytokines and enzymes in A549 lung epithelial cells in a manner devoid of S1P agonism.