A comparison of non-absorbable polymeric clips and staplers for laparoscopic appendiceal stump closure: analysis of 618 adult patients.

PURPOSE: The aim of this long-term study was the comparison of appendiceal stump closure with polymeric clips or staplers with respect to perioperative costs and surgical outcome under routine conditions in a university centre. METHODS: For this retrospective chart review, a total of 618 patients undergoing laparoscopic appendectomy for suspected acute appendicitis between 2010 and 2017 were reviewed: 410 patients in the stapler group and 208 patients in the clip group. The database contained demographic data, operation time, inflammation parameters, closure method of the stump, surgeon status, length of hospital stay, and complications as well as histology reports. The costs were also compared. RESULTS: Clip application was more likely among younger patients (mean age 33.6 years vs. 41.7 years). Histopathological evidence for appendiceal pathology was found in 96.6% of patients in the clip group and 99.5% of patients in the stapler group. Laparoscopic appendectomy in the clip group was more frequently performed by resident physicians (69.2%) than in the stapler group (57.8%). The mean postoperative stay was 2.9 days in the clip group and 3.7 days in the stapler group. The use of the polymeric clip resulted in considerable cost savings (19.94€ vs. 348.70€). CONCLUSIONS: The use of polymeric clips for appendiceal stump closure during appendectomy is safe and effective. The base of the appendix is amenable to clipping in 32% of appendectomies in adult patients. This study supports the use of polymeric clips over staplers to decrease cost and environmental impact.

Single ingestion of di-(2-propylheptyl) phthalate (DPHP) by male volunteers: DPHP in blood and its metabolites in blood and urine.

Di-(2-propylheptyl) phthalate (DPHP) is used as a plasticizer for polyvinyl chloride products. A tolerable daily intake of DPHP of 0.2 mg/kg body weight has been derived from rat data. Because toxicokinetic data of DPHP in humans were not available, it was the aim of the present work to monitor DPHP and selected metabolites in blood and urine of 6 male volunteers over time following ingestion of a single DPHP dose (0.7 mg/kg body weight). Concentration-time courses in blood were obtained up to 24 h for DPHP, mono-(2-propylheptyl) phthalate (MPHP), mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPHP), and mono-(2-propyl-6-oxoheptyl) phthalate (oxo-MPHP); amounts excreted in urine were determined up to 46 h for MPHP, OH-MPHP, oxo-MPHP, and mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP). All curves were characterized by an invasion and an elimination phase the kinetic parameters of which were determined together with the areas under the concentration-time curves in blood (AUCs). AUCs were: DPHP > MPHP > oxo-MPHP > OH-MPHP. The amounts excreted in urine were: oxo-MPHP > OH-MPHP> > cx-MPHP > MPHP. The AUCs of MPHP, oxo-MPHP, or OH-MPHP could be estimated well from the cumulative amounts of urinary OH-MPHP or oxo-MPHP excreted within 22 h after DPHP intake. Not considering possible differences in species-sensitivity towards unconjugated DPHP metabolites, it was concluded from a comparison of their AUCs in DPHP-exposed humans with corresponding earlier data in rats that there is no increased risk of adverse effects associated with the internal exposure of unconjugated DPHP metabolites in humans as compared to rats when receiving the same dose of DPHP per kg body weight.

El Niño and coral larval dispersal across the eastern Pacific marine barrier.

More than 5,000 km separates the frequently disturbed coral reefs of the Eastern Tropical Pacific (ETP) from western sources of population replenishment. It has been hypothesized that El Niño events facilitate eastward dispersal across this East Pacific Barrier (EPB). Here we present a biophysical coral larval dispersal model driven by 14.5 years of high-resolution surface ocean current data including the extreme 1997-1998 El Niño. We find no eastward cross-EPB connections over this period, which implies that ETP coral populations decimated by the 1998 bleaching event can only have recovered from eastern Pacific sources, in congruence with genetic data. Instead, rare connections between eastern and central Pacific reefs are simulated in a westward direction. Significant complexity and variability in the surface flows transporting larvae mean that generalized upper-ocean circulation patterns are poor descriptors of inter-regional connectivity, complicating the assessment of how climate change will impact coral gene flow Pacific wide.

Di-(2-propylheptyl) phthalate (DPHP) and its metabolites in blood of rats upon single oral administration of DPHP.

Di-(2-propylheptyl) phthalate (DPHP) does not act as a reproductive toxicant or endocrine disruptor in contrast to other phthalates. Considering adverse effects of phthalates to be linked to their metabolism, it was the aim of the present study to investigate in the rat the blood burden of DPHP and its metabolites as a basis for understanding the toxicological behavior of DPHP. Rats were administered single oral doses of DPHP of 0.7 and 100mg/kg body weight. Concentration-time courses of DPHP and metabolites were monitored in blood. The areas under the concentration-time curves in blood (AUCs), normalized for the dose of DPHP, showed the following order: DPHP

[Pathophysiology of peritonitis]. / Pathophysiologie der Peritonitis.

Despite intensive research efforts peritonitis leading to subsequent sepsis remains associated with a high mortality. The initial effector cells are the locally residing cells of the peritoneum, such as mesothelial cells, mast cells, macrophages and lymphocytes. Through the secretion of chemokines, an influx of neutrophils initially takes place followed by monocytes. The latter can differentiate into inflammatory macrophages. The non-directed activity of neutrophilic granulocytes is limited by the induction of apoptotic programs. Through the breaching of cytokines, bacteria and microbial products into the circulation, a systemic reaction in the sense of systemic inflammatory response syndrome (SIRS) or sepsis arises. This is viewed as a concomitant derailing of inflammatory as well as anti-inflammatory responses, which leads to extensive apoptosis of lymphocytes. The presentation of apoptotic cells leads to a strong immunosuppression. Due to the coexistence of hyperinflammation and immunosuppression, exact knowledge of the current immune status of the patient is a prerequisite in the development of immunotherapies for the treatment of sepsis.

Process design and control of a twin screw hot melt extrusion for continuous pharmaceutical tamper-resistant tablet production.

Hot melt extrusion (HME) is a well-known process within the plastic and food industries that has been utilized for the past several decades and is increasingly accepted by the pharmaceutical industry for continuous manufacturing. For tamper-resistant formulations of e.g. opioids, HME is the most efficient production technique. The focus of this study is thus to evaluate the manufacturability of the HME process for tamper-resistant formulations. Parameters such as the specific mechanical energy (SME), as well as the melt pressure and its standard deviation, are important and will be discussed in this study. In the first step, the existing process data are analyzed by means of multivariate data analysis. Key critical process parameters such as feed rate, screw speed, and the concentration of the API in the polymers are identified, and critical quality parameters of the tablet are defined. In the second step, a relationship between the critical material, product and process quality attributes are established by means of Design of Experiments (DoEs). The resulting SME and the temperature at the die are essential data points needed to indirectly qualify the degradation of the API, which should be minimal. NIR-spectroscopy is used to monitor the material during the extrusion process. In contrast to most applications in which the probe is directly integrated into the die, the optical sensor is integrated into the cooling line of the strands. This saves costs in the probe design and maintenance and increases the robustness of the chemometric models. Finally, a process measurement system is installed to monitor and control all of the critical attributes in real-time by means of first principles, DoE models, soft sensor models, and spectroscopic information. Overall, the process is very robust as long as the screw speed is kept low.

Encapsulated Brucella ovis Lacking a Putative ATP-Binding Cassette Transporter (ΔabcBA) Protects against Wild Type Brucella ovis in Rams.

This study aimed to evaluate protection induced by the vaccine candidate B. ovis ΔabcBA against experimental challenge with wild type B. ovis in rams. Rams were subcutaneously immunized with B. ovis ΔabcBA encapsulated with sterile alginate or with the non encapsulated vaccine strain. Serum, urine, and semen samples were collected during two months after immunization. The rams were then challenged with wild type B. ovis (ATCC25840), and the results were compared to non immunized and experimentally challenged rams. Immunization, particularly with encapsulated B. ovis ΔabcBA, prevented infection, secretion of wild type B. ovis in the semen and urine, shedding of neutrophils in the semen, and the development of clinical changes, gross and microscopic lesions induced by the wild type B. ovis reference strain. Collectively, our data indicates that the B. ovis ΔabcBA strain is an exceptionally good vaccine strain for preventing brucellosis caused by B. ovis infection in rams.

Rationale for the update of the European Pharmacopoeia general chapter 2.2.48. Raman spectroscopy.

Raman spectroscopy technique is widely used for the identification and characterisation of materials in the laboratory environment and, increasingly, for off-line, at-line, in-line and online Process Analytical Technologies (PAT) applications. The wide range of currently available Raman technologies had led to the requirement to update the existing General Chapter 2.2.48. The purpose of this reflection paper is to explain the rationale behind the establishment of the new wavenumber scale standards and peak position tolerances resulting from a multi-site, multi-instrument, inter-laboratory study of standards and, in particular, to discuss the results obtained with microscopes (including multi-point calibration) by the PAT Working Party.

[Modern treatment of an appendiceal mass]. / Moderne Therapie perityphlitischer Abszesse.

BACKGROUND: The recommendations for the treatment of an appendiceal mass are still controversial. The need for staged appendectomy is still under discussion. PATIENTS AND METHODS: In a retrospective study all patients with the diagnosis appendiceal mass (ICD 10 K35.32) treated in the surgical clinic of the University Clinic in Greifswald between June 1999 and June 2011 were analyzed. RESULTS: A total of 38 patients were included in the study whereby 17 patients (9 male and 8 female) were treated with drainage and antibiotics (group A) and 21 (14 male and 7 female) were treated by immediate surgery (group B). Nonsurgical therapy with drainage of the abscess was found to be efficient. Immediate surgical treatment was also effective and should be performed when signs of peritonitis exist. Interval appendectomy is not indicated.

[Disease-adapted closure of the appendicular stump in laparoscopic appendectomy]. / Stadiengerechte Versorgung der Appendixbasis im Rahmen der laparoskopischen Appendektomie.

The frequency of laparoscopic appendectomy has dramatically increased with it now being the standard procedure for acute appendicitis in many hospitals in Germany. Hence, these hospitals require the personnel, the technique as well as the expertise to guarantee a top standard and quality of appendectomies at all times. Only this will meet the requirements of the high case load and the socio-economical importance of appendectomies. The closure of the appendicular stump is a critical step of this procedure. The three most commonly used techniques consist of the endo-loop, the clip and the endo-stapler. The endo-stapler has the advantage of offering closure and transection of the appendix in one step; it can be employed in all cases of appendicular inflammation; and it allows a partial caecal resection. However, it is quite expensive. The clip and the endo-loop offer the same cost-effectiveness, yet the clip appears to be simpler in use compared to the loop. Also, sharing this feature with the stapler, it offers the possibility of closing and transecting the appendix before dissecting the mesoappendix. A disadvantage of the clip not being shared with the loop is the limitation of clips to appendicular diameters of only up to 16 mm. In summary, we propose a cost-effective disease-adapted closure of the appendicular stump employing the clip in standard appendectomies, with the endo-loop being a good alternative. If clip or loop cannot be applied the stapler is the technique of choice. In particular, it should be used if the base of the appendix is inflamed. Adopting this pathway helps to control the still somewhat higher costs of laparoscopic appendectomies compared to classical open appendectomies.

Surgical trauma and postoperative immune dysfunction.

BACKGROUND: In postoperative sepsis, mortality is increased due to the surgically induced immune dysfunction. Further causes of this traumatic effect on the immune system include burn injuries and polytrauma, as well as endogenous traumata like stroke. Several animal models have been defined to analyse the characteristics of trauma-induced immune suppression. This article will correlate our results from animal studies and clinical observations with the recent literature on postoperative immune suppression. METHODS: The previously described model of surgically induced immune dysfunction (SID) was performed in mice by laparotomy and manipulation of the small intestine in the antegrade direction. Blood samples were collected 6 and 72 h following SID to analyse the white blood cell count and corticosterone levels. To assess the postoperative immune status in humans, we analysed expression of HLA-DR on monocytes of 118 patients by flow cytometry prior to and 24, 48 and 72 h after surgery. RESULTS: The postoperative immune suppression in our SID model is characterised by lymphocytopenia and significantly increased corticosterone levels in mice dependent on the degree of surgical trauma. This is comparable to the postoperative situation in humans: major and especially long-lasting surgery results in a significantly reduced expression of HLA-DR on circulating monocytes. Previous studies describe a similar situation following burn injury and endogenous trauma, i.e. stroke. CONCLUSIONS: We suggest the completion of our previously published sepsis classification due to the immune status at the onset of sepsis: type A as the spontaneously acquired sepsis and type B as sepsis in trauma-induced pre-existing immune suppression.

Postoperative immune suppression in visceral surgery: characterisation of an intestinal mouse model.

BACKGROUND: Postoperatively acquired immune dysfunction is associated with a higher mortality rate in case of septic complications. As details of this severe clinical problem are still unknown, animal models are essential to characterise the mechanisms involved. METHODS: Mice were laparotomised and the small intestine was pressed smoothly in antegrade direction. For extension of trauma, the intestine was manipulated three times consecutively. Following this, the ex vivo cytokine release of splenocytes was determined. The degree of surgical trauma was analysed by detection of HMGB1 and IL-6 in serum and by neutrophil staining in the muscularis mucosae. RESULTS: We adapted the previously described animal model of intestinal manipulation to provide a model of surgically induced immune dysfunction. Following intestinal manipulation, the mice showed elevated serum levels of HMGB1 and IL-6 and increased infiltration of granulocytes into the muscularis mucosae. Ex vivo cytokine release by splenocytes was suppressed in the postoperative period. The degree of suppression correlated with the extent of surgical trauma. CONCLUSIONS: In this study, we describe a surgically induced immune dysfunction animal model, in which a significant surgical trauma is followed by an immune dysfunction. This model may be ideal for the characterisation of the postoperative immune dysfunction syndrome.

A quantitative assessment of the risks and cost savings of forgoing histologic examination of diminutive polyps.

BACKGROUND AND AIMS: Endoscopic prediction of polyp histology is rapidly improving to the point where it may not be necessary to submit all polyps for formal histologic assessment. This study aimed to quantify the expected costs and outcomes of removing diminutive polyps without subsequent pathologic assessment. METHODS: Cross-sectional analysis of a colonoscopy database for polyp histology; decision models that quantify effects on guideline-recommended surveillance and subsequent costs and consequences. The database was composed of consecutive colonoscopies from 1999 to 2004 at a single-institution tertiary care center. Patients were those found to have at least one diminutive polyp removed during colonoscopy, irrespective of indication. The main outcome measurements include up-front cost savings resulting from forgoing pathologic assessment; frequency and cost of incorrect surveillance intervals based on errors in histologic assessment; number needed to harm (NNH) for perforation and/or interval cancer. RESULTS: Incorrect surveillance intervals were recommended in 1.9% of cases when tissue was submitted for pathologic assessment and 11.8% of cases when it was not. Based on the annual volume of colonoscopy in the US, the annual up-front cost savings of forgoing the pathologic assessment would exceed a billion dollars. An upper estimate on the downstream costs and consequences of forgoing pathology suggests that less than 10% of the up-front savings would be offset and the NNH exceeds 11000. CONCLUSION: Endoscopic diagnosis of polyp histology during colonoscopy and forgoing pathologic examination would result in substantial up-front cost savings. Downstream consequences of the resulting incorrect surveillance intervals appear to be negligible.

Stimulation of TLR7 prior to polymicrobial sepsis improves the immune control of the inflammatory response in adult mice.

OBJECTIVE: The role of Toll-like receptor 7 (TLR7), so far regarded as a receptor for viral RNA, was evaluated in a murine sepsis model. MATERIAL: We used the colon ascendens stent peritonitis model (CASP) in female C57B/6 mice. R-848 (1.5 µg/g body weight) was injected intravenously prior to sepsis induction. METHODS: We determined levels of cytokines by CBA detection kit. Different cell populations were isolated from the spleen by magnetic cell separation and the expression of TLR7 was visualized by immunofluorescence staining. Bacterial load of organs was quantified by incubating suspensions on agar in colony forming units. RESULTS: R-848 application per se led to elevated cytokine levels in serum, spleen and peritoneal cavity. Expression of TLR7 on splenocytes was upregulated following CASP. Bacterial clearance in polymicrobial sepsis was significantly increased in spleen and peritoneum of mice pre-treated with the TLR7-agonist. Cytokine release was regulated in the peritoneum and spleen. Furthermore, apoptosis in thymus and spleen during polymicrobial sepsis was significantly decreased following TLR7 agonist application. CONCLUSIONS: TLR7 seems to be essential for pathogen defence not only in viral but also in bacterial infections. Pharmacological stimulation of this receptor prior to induction of sepsis improves the host's capacity to cope with pathogens.

Cs 894.3 nm laser pumped by photoassociation of Cs-Kr pairs: excitation of the Cs D(2) blue and red satellites.

Lasing on the D(1) transition (6P1/22-->6S1/22) of Cs has been observed by photoassociating Cs-Kr atomic pairs with a tunable, pulsed dye laser. Pumping of the blue or red satellites of the Cs D(2) line (62P3/2<==>62S1/2), peaking at approximately 841.1 nm and approximately 853 nm (respectively) in Cs/Kr/C(2)H(6) gas mixtures, provides a photodissociation laser in which the CsKr excimer parent molecule is not, at any point in the pumping process, in a bound electronic state. Relative to the absorbed pump pulse energy, laser slope efficiencies greater than or approximately 5% have been measured when the Cs number density is in the range of 5x10(14)-1.5x10(15) cm(-3) and the pump wavelength is 841.1 nm. Direct photoexcitation of the Cs 6P3/22 state at 852.1 nm under these conditions is a less efficient pathway for pumping the 894.3 nm laser, presumably as a result of competing nonlinear optical processes such as 1+2 resonantly enhanced multiphoton ionization of the alkali atom.

[Gastric schwannoma: a "typical" clinical course?]. / Abdominelles Schwannom : Ein "klassischer" Fallbericht?

Intra-abdominal schwannoma is a rare tumor entity. Although often detected incidentally, its diagnosis and surgical planning are difficult-as with all intramural intra-abdominal tumors. Puncturing is often not satisfying due to the inhomogeneous proliferation rates of different regions of the tumor. We describe the procedure using the example of a gastric schwannoma that was found incidentally. The leading symptom was perforation of a peptic stomach ulcer.

[Surgical trauma and postoperative immunosuppression]. / Operatives Trauma und postoperative Immunsuppression.

Abdominal surgery is regularly followed by immune dysfunction that can last for several days. In case of septic complications during this period, there is imminent danger of mortality due to reduced immune function. This fact leads to classification of sepsis in regard to its genesis: spontaneously acquired sepsis type A is distinguishable from sepsis type B, which is acquired postoperatively. The main difference between these types is the immunologic condition at the time point of sepsis development. Postoperative immune dysfunction can be described by several parameters, i.e. reduction of HLA-DR expression on monocytes and increased apoptosis of T lymphocytes. A direct correlation exists between magnitude of immune dysfunction and complexity of the previous surgical trauma. For the first time it is now possible to study this phenomenon of postoperative immune dysfunction by use of an adequate animal model. Intestinal manipulation in mice fulfils the necessary criteria to serve as a model of surgically induced immune dysfunction.

Online UV-visible spectroscopy and multivariate curve resolution as powerful tool for model-free investigation of laccase-catalysed oxidation.

The laccase-catalysed transformation of indigo carmine (IC) with and without a redox active mediator was studied using online UV-visible spectroscopy. Deconvolution of the mixture spectra obtained during the reaction was performed on a model-free basis using multivariate curve resolution (MCR). Thereby, the time courses of educts, products, and reaction intermediates involved in the transformation were reconstructed without prior mechanistic assumptions. Furthermore, the spectral signature of a reactive intermediate which could not have been detected by a classical hard-modelling approach was extracted from the chemometric analysis. The findings suggest that the combined use of UV-visible spectroscopy and MCR may lead to unexpectedly deep mechanistic evidence otherwise buried in the experimental data. Thus, although rather an unspecific method, UV-visible spectroscopy can prove useful in the monitoring of chemical reactions when combined with MCR. This offers a wide range of chemists a cheap and readily available, highly sensitive tool for chemical reaction online monitoring.

[Optical performance of multifocal intraocular lenses. Investigation of the Array SA40N vs. Acri. Twin at the "physical eye" according to Reiner and Jacobi]. / Abbildungseigenschaften multifokaler Intraokularlinsen. Untersuchung der Array SA40N vs. Acri.Twin am "physikalischen Auge" nach Reiner und Jacobi.

BACKGROUND: Reduced contrast sensitivity, glare disability and insufficient bifocality are the main drawbacks of multifocal intraocular lenses (IOL). The bilateral implantation of diffractive IOL with an asymmetrical light distribution for distance and near focus is an alternative concept that aims to improve the contrast sensitivity and bifocality of conventional multifocal IOL. PATIENTS AND METHODS: The optical performance of monofocal (PhacoFlexII SI40) and multifocal IOL (Array SA40N; Acri. Twin 737D/733D) was quantitatively assessed in 18 healthy probands and qualitatively determined by digital photographic recording using an optical apparatus, the "physical eye", according to Reiner and Jacobi. Vision examination included standard tests of distance and near visual acuity, contrast sensitivity and low contrast visual acuity testing under varying pupil size using a video acuity tester. RESULTS: Distance visual acuity was significantly superior with the SI40 and distant-dominant 737D compared to the SA40N and near-dominant 733D. At near, the 733D had the best performance. Contrast sensitivity was better with the 737D than the SA40N when both were compared with the SI40. No normal contrast sensitivity could be determined with the 733D because of the optical phenomenon of 'spurious resolution'. Variation in pupil size had less impact on contrast acuity with the Acri. Twin IOL compared to the SI40 and SA40N. Photographic testing revealed better edge contrast with the Acri. Twin than the SA40N. CONCLUSIONS: The optical performance of multifocal IOL correlates with the properties of physical light distribution. Differences in edge contrast may be discerned using photographic recording.