STRONGHOLD first-year results of biomechanically calculated abdominal wall repair: a propensity score matching.

PURPOSE: Every year around 70,000 people in Germany suffer from an abdominal incisional hernia that requires surgical treatment. Five years after reconstruction about 25% reoccur. Incisional hernias are usually closed with mesh using various reconstruction techniques, summarized here as standard reconstruction (SR). To improve hernia repair, we established a concept for biomechanically calculated reconstructions (BCR). In the BCR, two formulas enable customized patient care through standardized biomechanical measures. This study aims to compare the clinical outcomes of SR and BCR of incisional hernias after 1 year of follow-up based on the Herniamed registry. METHODS: SR includes open retromuscular mesh augmented incisional hernia repair according to clinical guidelines. BCR determines the required strength (Critical Resistance to Impacts related to Pressure = CRIP) preoperatively depending on the hernia size. It supports the surgeon in reliably determining the Gained Resistance, based on the mesh-defect-area-ratio, further mesh and suture factors, and the tissue stability. To compare SR and BCR repair outcomes in incisional hernias at 1 year, propensity score matching was performed on 15 variables. Included were 301 patients with BCR surgery and 23,220 with standard repair. RESULTS: BCR surgeries show a significant reduction in recurrences (1.7% vs. 5.2%, p = 0.0041), pain requiring treatment (4.1% vs. 12.0%, p = 0.001), and pain at rest (6.9% vs. 12.7%, p = 0.033) when comparing matched pairs. Complication rates, complication-related reoperations, and stress-related pain showed no systematic difference. CONCLUSION: Biomechanically calculated repairs improve patient care. BCR shows a significant reduction in recurrence rates, pain at rest, and pain requiring treatment at 1-year follow-up compared to SR.

Standardized suturing can prevent slackening or bursting suture lines in midline abdominal incisions and defects.

PURPOSE: Incisional hernias often follow open abdominal surgery. A small-stitch-small-bite suture might close the incision durably. We analyzed specific details of this closure technique and assessed their influence on the closure stability. METHODS: The effects of cyclic loads, simulating coughs were investigated on a bench test. We prepared porcine bellies in the median line and bovine flanks parallel to the muscle fibers with 15 cm long incisions. Then we punched round or rhomboid defects with a diameter of 5-10 cm into the center of the incision. Monomax® 2-0 and Maxon® 1 and 2-0 were used as suture materials. We tested the durability of the closure with pressure impacts of 210 mmHg repeated 425 times. Throughout the experiments, we modified the suturing technique, the surgeon, the tissue tension, the defect size and shape and the suture diameter. RESULTS: Standardizing the suture technique improved the durability of the closure significantly. Any other variations showed minor influences after standardization. All incisions with round defects up to 7.5 cm width withstood 425 impacts using standardized suturing. Unstandardized sutures failed in all cases. When closing an incision with a 10 cm wide defect, the tissues ruptured frequently next to the suture line. We defined criteria to standardize this suturing technique. For the first time, we developed a suture factor related to the durability of a sutured tissue closure. We integrated the suture factor into the concept of biomechanically durable repairs. CONCLUSIONS: Suturing the abdominal wall with a standardized suturing technique improves its durability significantly.

Tolerability and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) for warfarin and non-warfarin reversals.

PURPOSE: Current guidelines favor 4F-PCC over plasma for warfarin reversal. Uncertainty remains on its thrombotic risk and hemostatic effectiveness when used for direct-acting oral anticoagulants (DOACs), transplants, massive transfusion protocols (MTP), and non-anticoagulated patients. This study sought to evaluate the tolerability and effectiveness of 4F-PCC in a real-world setting. MATERIALS AND METHODS: This was a retrospective study of adults who received 4F-PCC from March 2014 to December 2015. The primary outcome was thromboembolic events within 14 days. The secondary outcome was hemostatic effectiveness within 24 h. RESULTS: The final analysis included 212 patients. Primary reversal indication was major bleed in 165 patients (77.8%) and emergent surgery in 47 patients (22.2%). Thromboembolism occurred in 22 patients (10.4%), more in emergent surgery than major bleed reversals (17% and 8.5%, respectively). MTP and heart transplant patients had the highest thromboembolic event rates (44.4% and 28.6%, respectively). Hemostatic effectiveness was 65.8% (68% in major bleed and 58.1% in emergent surgery). DOAC patients achieved hemostasis most often (78.9%). Administration of any reversal agent, major surgery within 14 days, and MTP activation were significant predictors of thromboembolism. CONCLUSIONS: Use of 4F-PCC in this real-world setting was associated with variable thromboembolic and hemostatic effectiveness rates based on the indication for reversal.

Multi-hospital analysis of antimicrobial usage and resistance trends.

We report a pilot study comparing antimicrobial usage and antimicrobial resistance trends for prominent nosocomial pathogens between 1994-1996. A convenience sample of ten hospitals participated in this retrospective review. We found a large variation in antimicrobial use and resistance trends and that many hospitals did not have data readily available to evaluate drug usage and resistance rates. A significant strong positive correlation was observed between the usage of ceftazidime and the prevalence of ceftazidime resistant Pseudomonas aeruginosa (r = 0.8, p = 0.005) and of ceftazidime resistant Enterobacter species (r = 0.8, p = 0.02). The presence of antibiotic control policies correlated with lower rates of some resistant strains and less antibiotic use. Our findings can be a useful starting point for hospitals that want to systematically measure antimicrobial use and resistance. Hospital laboratories, pharmacies, and infection control departments must work together to develop databases that will facilitate such measurements.

[Effect of common head gear on horses]. / Uber die Wirkung gebräuchlicher Zäumungen auf das Pferd.

The functions of the most common head-gears for horses are analysed from a biomechanical point of view. With the exception of the stable halter are all of them designed to enlarge the tensile forces transmitted through the reins or the longe, and to concentrate the enlarged forces on sensitive parts of the horse's head: the nose, or the lips, mandible and tongue. Since the direction, duration and size of these tensile forces are the essential factors to modulate signals for controlling the horse, a device has been developed to measure, or at least roughly quantify these forces. The mechanical characteristics of bosal, caveçon, serreta, kappzaum and hackamore are demonstrated and compared with those of the two major types of bits: those with and without levers.

Lack of beneficial effect of COX-2 inhibitors in an experimental model of colitis.

Expression of the COX-2 enzyme has been reported in animal models of inflammatory bowel disease (IBD) as well as in patients affected by ulcerative colitis and Crohn's disease. Recently, selective inhibitors of COX-2 have become available. In this study we have evaluated three highly selective COX-2 inhibitors, NS-398, SC-58125 and PD-138387, on the trinitro-benzene sulfonic acid (TNBS) model of colitis in rats. Daily oral administration of the three compounds evaluated up to a dose of 100 mg/kg failed to significantly modify any of the parameters evaluated. Our data show that despite their potent extraintestinal antiinflammatory activity, COX-2 inhibitors do not seem to have any beneficial effect in TNBS colitis and raise the question whether this therapeutic approach would be beneficial in patients with IBD.

Effects of novel anti-inflammatory compounds on healing of acetic acid-induced gastric ulcer in rats.

Nonsteroidal anti-inflammatory drugs often cause development of significant GI lesions. Selective inhibitors of prostaglandin G/H synthase/cyclooxygenase-2 (PGHS-2) enzyme and some dual inhibitors of PGHS/5-lipoxygenase (5-LO) enzymes have been reported to be potent anti-inflammatory compounds that carry a much lower risk of having GI irritating effects. We have evaluated the anti-inflammatory effect and the GI safety profile of three new anti-inflammatory compounds: the selective PGHS-2 inhibitors NS-398 and PD 138387 and the PGHS/5-LO dual inhibitor PD 137968. All the compounds tested showed an anti-inflammatory activity in the carragenan footpad edema test in rats. None of these compounds caused either gastric damage 4 h after p.o. administration of 100 mg/kg in rats or inhibition of PGE2 synthesis in the stomach. However, when administered p.o. at an effective anti-inflammatory dose to rats with pre-existing acetic acid-induced gastric ulcer, NS-398 caused a statistically significant delay of ulcer healing. No impairment of the ulcer healing was observed with the other compounds evaluated. Derivatives of 2,6-di-tert-butylphenol, whose members may act as PGHS-1/PGHS-2 inhibitors, selective PGHS-2 inhibitors or PGHS/5-LO dual inhibitors, are novel anti-inflammatory compounds that are devoid of GI irritating effects and do not affect the rate of pre-existing gastric ulcer healing.

Role of metalloproteinases in the development and healing of acetic acid-induced gastric ulcer in rats.

BACKGROUND/AIMS: Matrix metalloproteinases (MMPs) are believed to be active in connective tissue remodeling associated with various physiological processes and in pathological conditions such as cancer and arthritis. However, the role of MMPs in gastrointestinal ulceration has not been clearly established. Therefore, the aim of this study was to examine the role of collagenase and gelatinases A and B in the development and healing of acetic acid-induced gastric ulcer in rats. METHODS: Gastric ulcer was induced by injecting 20 microliters glacial acetic acid into gastric wall of rat stomachs. To examine whether changes in the ulcer formation and healing phase correlate with MMP activity, Triton X-100/CaCl2 and Tris/CaCl2 (60 degrees C) extracts of stomachs were prepared from controls and animals killed 24 h (formation phase) and 7 days (healing phase) after acetic acid administration. Total collagenase and gelatinase activities were measured using (H3)labeled-acetylated type I collagen or gelatin as substrate, respectively, prepared from rat skin. RESULTS: Twenty-four hours after administration of acetic acid, the mean area of ulcer crater was 51.2 mm2. By day 7, the mean size of ulcer crater was reduced to 35.9 mm2. The mean activity of collagenase in gastric tissue from controls animals was 0.007 U/g tissue. In acetic acid-treated rats, this activity increased to 2.18 U/g at 24 h and declined to 0.69 U/g by day 7. Similarly, total gelatinase activity increased from 20.5 U/g tissue (controls) to 28.8 U/g at 24 h and declined to 23.9 U/g at day 7. Gelatinzymography revealed that gelatinase B levels were greatly increased at 24 h and declined by day 7, whereas the gelatinase A levels remained constant. CONCLUSIONS: The data showed that the formation of acetic acid-induced ulcer in rats is accompanied by an elevation of collagenase and gelatinase B that gradually tend to return to control values during the healing phase.

Is elastic energy storage of quantitative relevance for the functional morphology of the human locomotor apparatus?

Elastic storage of energy in the vertebrate locomotor apparatus is supposed to be an important functional factor in cyclic and acyclic movements. In terms of physics, for humans a proof for the occurrence and quantitative relevance of this phenomenon in vivo and under physiological conditions has been missing until now. In addition to the large amount of plausible, but inconclusive information about elasticity in humans and animals, we describe a simple experiment to prove the existence of quantitatively relevant elastic energy storage in the human locomotor apparatus. Ten volunteers (5 female, 5 male) each assumed a relaxed, upright posture on a steel platform. After the release of a support, the volunteers and the platform fell for a defined distance of 33 mm. Loaded with the volunteers, the platform fell significantly (p < 0.001) faster than predicted by the laws of stiff body mechanics (50 vs. 82 ms). For a minimum time of 50 ms, the human locomotor apparatus is able to support an average external power output of more than 400 W by means of an energy transfer of more than 20 J. During the fall, no EMG activities of the ankle flexors could be recorded. We conclude that the acceleration of the platform fall is induced by elastic elements serving as energy sources. Elastic energy storage is of quantitative relevance for the functional morphology and biomechanics of the human locomotor apparatus.

Increased gastroduodenal concentrations of transforming growth factor alpha in adaptation to aspirin in monkeys and rats.

BACKGROUND & AIMS: The mechanism by which gastric mucosa becomes more resistant to damage by repeated aspirin administration is not known. Transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) prevent drug-induced gastric injury. The aim of this study was to determine whether gastroduodenal tissue levels of TGF-alpha and EGF protein were altered during adaptation to aspirin-induced injury in monkeys and rats in vivo. METHODS: Animals were given aspirin daily for up to 28 days. Gross mucosal injury was assessed by computerized image analysis in rats and by endoscopy in monkeys. Mucosal concentrations of TGF-alpha and EGF were quantitated by radioimmunoassays from endoscopic biopsy samples in monkeys and from scraped mucosa in rats. RESULTS: Long-term administration of aspirin caused a significant increase in gastric and duodenal tissue levels of TGF-alpha in monkeys and rats; the increased levels of TGF-alpha significantly correlated with the decrease in aspirin-induced injury. No change in the gastroduodenal tissue levels of EGF was observed. Adaptation was not associated with any significant change in basal gastric acid secretion in monkeys and occurred despite a significant decrease in gastric mucin in rats. CONCLUSIONS: Adaptation of the gastric mucosa to the damaging effect of aspirin is associated with a significant and specific increase in TGF-alpha protein in the gastroduodenum.

BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats.

The effect of BPC-15 (Booly Protection Compound-15) was evaluated in a rat model of colonic injury. A single intracolonic administration of trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol induces severe colonic damage, which is characterized by areas of necrosis surrounded by areas of acute inflammation. The damage is associated with high myeloperoxidase (MPO) activity, mainly as a reflection of neutrophilic infiltration into the damaged tissue. In this study, 1 hr before a single intracolonic administration of 50 mg/kg of TNBS in 50% ethanol, the animals were treated with one of the following doses of BPC-15: 0.0001, 0.001, 0.01, 0.1, 1 or 10 nmol/kg administered i.p. or with a dose of 10 nmol/kg administered intracolonically. The animals were sacrificed 3 days later and the extent of colonic necrosis and hyperemia was measured with an image analyzer. The i.p. administration of BPC-15 significantly reduced the extent of TNBS-induced colonic damage in a dose-dependent manner. This was associated with a statistically significant and dose-dependent reduction in colonic tissue MPO activity. At the dose tested (10 nmol/kg), intracolonic administration of BPC-15 did not significantly reduce either the extent of the colonic damage or the increase in MPO activity induced by TNBS. In conclusion, this study showed that i.p. administration of BPC-15 reduced TNBS-induced colonic damage in rats.

Langerhans cell density in normal human oral mucosa and skin: relationship to age, smoking and alcohol consumption.

The immune function of skin has been studied extensively and it has been suggested that epidermal Langerhans cell (LC) density and function decreases with increasing age. Little is known, however, about the effect of age on oral mucosal LC. Cryostat sections from biopsies of buccal mucosa, lip, hard palate, lateral border of tongue, floor of mouth and abdominal skin, obtained from 91 subjects (aged 16-96 yr), were reacted immunocytochemically with a monoclonal antibody against CD1a and then LC density was expressed as LC/mm epithelial surface length. No significant effect of age on mucosal or skin LC density was found, whilst a history of smoking was associated with an increase in LC density in lateral border of tongue and in biopsies of labial mucosa taken from men (P < 0.05). There was no significant difference between LC density in men and women in oral mucosa. Oral mucosal LC may therefore form a relatively stable population in the adult and thus the increased incidence of mucosal disease in the elderly may be the result of subtle changes in cell mediated immune function rather than changes in LC density.

Effect of transforming growth factor-alpha on gastric acid secretion in rats and monkeys.

The effect of transforming growth factor-alpha was studied in histamine-stimulated gastric acid secretion in monkeys and in pylorus-ligated rats. In monkeys, transforming growth factor-alpha given intravenously in a stepwise manner gradually reduced gastric acid secretion. A dose of 0.1 mmol/kg induced about a 50% inhibition of gastric acid output, while about 100% inhibition of the same parameter, was observed after a dose of 1 nmol/kg. Following a single administration of 1 nmol/kg intravenously in monkey, the maximum inhibitory effect on gastric acid output was reached 60 min after the administration of the drug, when a 91.8% inhibition was observed. Pretreatment values were reached 210-240 min after transforming growth factor-alpha administration. In pylorus-ligated rats, transforming growth factor-alpha, at doses of 9 and 18 nmol/kg produced an almost complete inhibition of gastric acid secretion. In this model, the ED50 was calculated to be 4.5 nmol/kg. Comparison with epidermal growth factor on the same models of gastric acid secretion showed that these two compounds have similar inhibitory potency. However, the effect of transforming growth factor-alpha on gastric acid secretion in monkeys was shorter lasting than that of epidermal growth factor.

Effect of h-EGF and h-EGF 1-48 on histamine-stimulated gastric acid secretion in rats and monkeys.

The effect of human epidermal growth factor (h-EGF) and its derivative human epidermal growth factor 1-48 (h-EGF 1-48) on histamine-stimulated gastric acid secretion was studied in monkeys and rats. In monkeys, both h-EGF and h-EGF 1-48 given intravenously (i.v.) in a stepwise manner and in doses ranging from 0.01 to 10 nmol/kg, gradually suppressed gastric acid secretion. At the highest dose tested, both compounds essentially abolished gastric acid output. In the same animals, i.v. administration of 1 nmol/kg of h-EGF or h-EGF 1-48 caused an inhibition of gastric acid output that reached a peak at 90 and 60 min after the administration of h-EGF or h-EGF 1-48 respectively. After this maximum gastric inhibitory effect, a gradual return toward pre-injection values was observed. In rats, after subcutaneous (sc) administration, both h-EGF and h-EGF 1-48 dose-dependently inhibited histamine-stimulated gastric acid output as measured 60 min after the administration of the compounds. The maximum inhibitory activity on gastric acid output, observed at a dose of 100 nmol/kg, was 74.4% and 76.0% for h-EGF and h-EGF 1-48 respectively. The same dose of both compounds, however, failed to significantly inhibit gastric acid secretion when administered orally. In all the studies h-EGF 1-48 showed activity and potency comparable to h-EGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of platelet-derived growth factor-BB on indomethacin-induced gastric lesions in rats.

The effect of platelet-derived growth factor-BB (PDGF-BB) was evaluated in rats with indomethacin-induced gastric lesions. Animals were treated with either saline solution or several doses of PDGF-BB given orally. Rats treated with 0.1 nmol/kg PDGF-BB showed a statistically significant reduction of gastric damage. Higher doses did not produce any further reduction of gastric damage, and a return toward control values was observed. The effect on lesions was independent of inhibition of gastric acid secretion, since a dose of 0.1 nmol/kg of this growth factor failed to modify gastric acid secretion stimulated by pylorus ligation.

Regional variation in Langerhans cell distribution and density in normal human oral mucosa determined using monoclonal antibodies against CD1, HLADR, HLADQ and HLADP.

The distribution, density and activation of Langerhans cells (LC) has been established in biopsies of normal human buccal mucosa, hard palate, lateral border and dorsum of tongue, floor of mouth and lip taken from sudden death post mortems. LC were identified in cryostat sections with monoclonal antibodies against CD1, HLADR, HLADQ and HLADP using an immunoalkaline phosphatase technique. The use of post mortem material was validated by comparison with biopsies taken from volunteers. LC were predominantly situated in the basal and immediately suprabasal layers of the epithelium. In floor of mouth, lip, lateral border and dorsum of tongue the cells were found along the length of the epithelium. In buccal mucosa, although LC showed fundamentally a similar distribution, a tendency to cluster around the connective tissue papillae was also noted. In hard palate LC were found parallel to the surface in the mid zone of the epithelium. No evidence of LC free areas was found. Dorsum of tongue had the highest density of LC per mm epithelial surface length (28.3 cells per mm) which was significantly greater (P less than 0.05) than buccal mucosa (25.2) which in turn had significantly more cells (P less than 0.05) than lip (22.4). The lowest density of LC was found in lateral border of tongue (17.6), hard palate (17.6) and floor of mouth (16.7). These sites had significantly fewer cells than lip, buccal mucosa and dorsum of tongue (P less than 0.05). Class II MHC molecules are necessary for antigen presentation and in all sites except buccal mucosa there was no significant difference between the number of cells expressing CD1, HLADR, HLADQ and HLADP.(ABSTRACT TRUNCATED AT 250 WORDS)

The permeability of human oral mucosa and skin to water.

Specimens from four regions of oral mucosa (palate, buccal mucosa, lateral border of the tongue, and the floor of the mouth) and of abdominal skin were taken from 58 individuals at autopsy, for determination of permeability constants (Kp) to tritium-labeled water. Comparisons between fresh specimens and those stored at -80 degrees C revealed no significant effect on Kp as a result of freezing; similar results were found with use of specimens from corresponding regions of the pig. Values for Kp were significantly different for all of the tissue regions examined and ranged from 44 +/- 4 x 10(-7) cm/min for skin to 973 +/- 33 x 10(-7) cm/min for the floor of the mouth, which was the most permeable region. Similar differences were evident among corresponding regions of porcine oral mucosa and skin. Moreover, the Kp values obtained for human tissues were not significantly different from those of the pig, except for the floor of the mouth, which was more permeable in human than in pig tissue. The results reveal interesting differences in the permeability of human oral mucosa that might be related to susceptibility to mucosal disease in those conditions where local extrinsic etiological agents are implicated.

Penetration pathways of different compounds through epidermis and oral epithelia.

The permeability of skin and oral mucosa to various compounds has been measured but the actual pathways substances take in traversing the epithelia have not been identified. In this study, radiolabelled cholesterol, ethanol or water were placed on the surface of porcine skin, keratinized gingiva, or nonkeratinized floor of mouth mucosa, and incubated at 37 degrees C for 2 h. The tissue was then snap-frozen, and sectioned in a cryostat, picked up on precoated slides and exposed at -20 degrees C for 40 days for light microscopic autoradiography. Some tissues were freeze-dried and directly embedded in low viscosity resin and prepared for electron microscopic autoradiography. Examination of autoradiographs revealed silver grains over, or adjacent to, intercellular spaces. Counts of the grains over the extra- and intracellular compartments were made in random light and electron microscope fields. For all compounds and tissue regions, there were significantly more (p less than 0.05) grains over the intercellular spaces than over the cells. The results indicate that the intercellular compartment is the predominant route for compounds moving across the superficial barrier layer of epidermis and oral epithelia. The nature of the intercellular material is, thus, a primary determinant of epithelial permeability.