[Prehospital management of acute coronary syndrome in patients on long-term direct oral anticoagulant treatment]. / Prähospitale Behandlung des akuten Koronarsyndroms unter DOAK-Dauertherapie.

BACKGROUND: Despite an increasing incidence of patients suffering from acute coronary syndrome (ACS) under simultaneous treatment with direct oral anticoagulants (DOAC), neither sufficient scientific data nor uniform guidelines for the anticoagulation treatment of these patients are currently available. OBJECTIVE: The aim of this study was to determine the current practice of preclinical treatment of ACS in patients under DOAC treatment. MATERIAL AND METHODS: An internet and paper-based survey of emergency physicians, specialists of internal medicine, anesthesiologists, emergency and intensive care physicians was performed concerning the prehospital treatment of ACS in patients under long-term DOAC treatment. RESULTS: Overall, 284 questionnaires were answered. Substantial differences in the current treatment of ACS under long-term DOAC therapy were identified. While 39% of the respondents stated that they administer a combination treatment of heparin and acetylsalicylic acid (ASA), 36% renounced the administration of heparin. If a dose reduction was performed, 71% answered that they reduce the heparin dosage. Also, in cases of ST-segment elevation myocardial infarction 48% of the physicians renounced the administration of heparin. CONCLUSION: In Germany there is currently a heterogeneous practice of emergency treatment of ACS patients under DOAC therapy with respect to the administration of heparin and ASA. Therefore, guidelines of the specialist medical societies should address the prehospital emergency anticoagulation management of ACS in patients under therapy with DOAC, which correspond to the needs of patients and emergency physicians.

[Skill retention using extraglottic airways in out-of-hospital emergencies: efficacy and long-term results of simulator-based medical education : A prospective follow-up study]. / Routineerhalt beim Umgang mit extraglottischen Atemwegen im Rettungsdienst: Effektivität und Nachhaltigkeit einer simulatorbasierten Ausbildung : Eine prospektive 2­zeitige Simulatorstudie.

OBJECTIVE: For emergency medicine personnel (EMP), there is little evidence concerning the adequate timing for refresher courses to maintain routine in the application of extraglottic airways. The aim of this study was to evaluate the efficacy and long-term results of a simulator-based education concept teaching the basic airway management skills with extraglottic airways for EMP and also to draw conclusions concerning the adequate time interval for refresher courses. METHODS: By use of an explorative, prospective simulator-study with nonphysician EMP, airway management skills using the Larynxmaske Supreme® (LMA­S) after an introduction lecture were examined. The application of an endotracheal tube (ETT) served as control. Time for preparation of the airway devices, insertion success, and resulting apnea time were assessed immediately after the first introduction lecture (t1) and unannounced 9-12 months thereafter (t2). RESULTS: Comparison of the times for preparation of the LMA­S at t1 and t2 demonstrated similar results. After the introduction lecture, all paramedics were able to insert the LMA­S successfully after maximal 2 attempts; 9-12 months later success rates with the LMA­S were unchanged. Apnea time during airway management was shorter with the LMA­S compared to the ETT (p < 0.01). Times needed for preparation of the airway devices were similar. CONCLUSION: The results of this simulator study indicate that a standardized introduction lecture is appropriate to ensure long-lasting procedural skills up to 12 months, so that subsequent refresher courses in basic airway management with the LMA­S once a year may be adequate. A simulator-based education in basic airway management skills with extraglottic airways is recommended for facilitation of further clinical education according to the current guidelines.

Vasomotion of mice mesenteric arteries during low oxygen levels.

BACKGROUND: Ischemia of intestinal organs is a main cause of complications in surgical intensive care patients. Changes in the tonus of arteries contributing to vascular resistance play an important role in the determination of blood flow and thus oxygen supply of various abdominal organs. It is generally acknowledged that hypoxia itself is able to alter arterial tonus and thus blood flow. METHODS: The present study compared the effects of various degrees of hypoxia on second-order mesenteric arteries from male C57BL/6J mice. After vessel isolation and preparation, we assessed vessel diameter using an arteriograph perfusion chamber. Investigating mechanisms promoting hypoxia-induced vasodilatation, we performed experiments in Ca2+-containing and Ca2+-free solutions, and furthermore, Ca2+-influx was inhibited by NiCl2, eNOS-/--, and TASK1-/--mice were investigated too. RESULTS: Mild hypoxia 14.4% O2 induced, in 50% of mesenteric artery segments from wild-type (wt) mice, a vasodilatation; severe hypoxia recruited further segments responding with vasodilatation reaching 80% under anoxia. However, the extension of dilatation of luminal arterial diameter reduced from 1.96% ± 0.55 at 14.4% O2 to 0.68% ± 0.13 under anoxia. Arteries exposed to hypoxia in Ca2+-free solution responded to lower oxygen levels with increasing degree of vasodilatation (0.85% ± 0.19 at 14.4% O2 vs. 1.53% ± 0.42 at 2.7% O2). Inhibition of voltage-gated Ca2+-influx using NiCl2 completely diminished hypoxia-induced vasodilatation. Instead, all arterial segments investigated constricted. Furthermore, we did not observe altered hypoxia-induced vasomotion in eNOS-/-- or TASK1-/- mice compared to wt animals. CONCLUSIONS: The present study demonstrated that hypoxic vasodilatation in mice mesenteric arteries is mediated by a NO-independent mechanism. In this experimental setting, we found evidence for Ca2+-mediated activation of ion channels causing hypoxic vasodilatation.

Susceptibility of Snails to Infection with Schistosomes is influenced by Temperature and Expression of Heat Shock Proteins.

The freshwater snail, Biomphalaria glabrata is the obligate intermediate host for the transmission of the parasitic trematode, Schistosoma mansoni the causative agent of the chronic debilitating neglected tropical disease, schistosomiasis. We showed previously that in juvenile snails, early and significant induction of stress manifested by the expression of stress proteins, Hsp 70, Hsp 90 and reverse transcriptase (RT) of the non- LTR retrotransposon, nimbus, is a characteristic feature of juvenile susceptible NMRI but not resistant BS-90 snails. These latter, however, could be rendered susceptible after mild heat shock at 32°C, revealing that resistance in the BS-90 resistant snail to schistosomes is a temperature dependent trait. Here we tested the hypothesis that maintenance of BS-90 resistant snails at the permissive temperature for several generations affects the resistance phenotype displayed at the non-permissive temperature of 25°C. The progeny of BS-90 snails bred and maintained through several generations (F1 to F4) at 32°C were susceptible to the schistosome infection when returned to room temperature, shedding cercariae at four weeks post-infection. Moreover, the study of expression levels of the heat shock protein (Hsp) 70 protein by ELISA and western blot analysis, showed that this protein is also differentially expressed between susceptible and resistant snails, with susceptible snails expressing more protein than their resistant counterparts after early exposure to wild-type but not to radiation-attenuated miracidia. These data suggested that in the face of global warming, the ability to sustain a reduction in schistosomiasis by using refractory snails as a strategy to block transmission of the disease might prove challenging since non-lethal elevation in temperature, affects snail susceptibility to S. mansoni.

[Patient with a Fontan circulation undergoing caesarean section: Anesthesiological management]. / Sectio caesarea bei einer Patientin mit Fontan-Zirkulation : Anästhesiologisches Management.

Adults suffering from congenital heart diseases (CHD) represent a challenge to anesthesiologists because of the diverse pathologies, complex pathophysiology and special treatment strategies. Due to improved therapeutic options for CHD, patient quality of life and life expectancy is increasing, leaving them as a growing population including pregnant patients with CHD. This article presents the main principles of the pathophysiology and anesthesiological management of pregnant patients living with a Fontan circulation based on a case report, which was complicated by an aortic coarctation and atonic uterine hemorrhage.

Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells.

BACKGROUND: In recent years, the rapidly advancing field of low-temperature atmospheric pressure plasmas has shown considerable promise for future translational biomedical applications, including cancer therapy, through the generation of reactive oxygen and nitrogen species. METHOD: The cytopathic effect of low-temperature plasma was first verified in two commonly used prostate cell lines: BPH-1 and PC-3 cells. The study was then extended to analyse the effects in paired normal and tumour (Gleason grade 7) prostate epithelial cells cultured directly from patient tissue. Hydrogen peroxide (H2O2) and staurosporine were used as controls throughout. RESULTS: Low-temperature plasma (LTP) exposure resulted in high levels of DNA damage, a reduction in cell viability, and colony-forming ability. H2O2 formed in the culture medium was a likely facilitator of these effects. Necrosis and autophagy were recorded in primary cells, whereas cell lines exhibited apoptosis and necrosis. CONCLUSIONS: This study demonstrates that LTP treatment causes cytotoxic insult in primary prostate cells, leading to rapid necrotic cell death. It also highlights the need to study primary cultures in order to gain more realistic insight into patient response.

DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation.

Prostate cancer (CaP) is mostly composed of luminal-like differentiated cells, but contains a small subpopulation of basal cells (including stem-like cells), which can proliferate and differentiate into luminal-like cells. In cancers, CpG island hypermethylation has been associated with gene downregulation, but the causal relationship between the two phenomena is still debated. Here we clarify the origin and function of CpG island hypermethylation in CaP, in the context of a cancer cell hierarchy and epithelial differentiation, by analysis of separated basal and luminal cells from cancers. For a set of genes (including GSTP1) that are hypermethylated in CaP, gene downregulation is the result of cell differentiation and is not cancer specific. Hypermethylation is however seen in more differentiated cancer cells and is promoted by hyperproliferation. These genes are maintained as actively expressed and methylation-free in undifferentiated CaP cells, and their hypermethylation is not essential for either tumour development or expansion. We present evidence for the causes and the dynamics of CpG island hypermethylation in CaP, showing that, for a specific set of genes, promoter methylation is downstream of gene downregulation and is not a driver of gene repression, while gene repression is a result of tissue-specific differentiation.

Hypercalcemia in renal transplant patients: prevalence and management in Canadian transplant practice.

Hypercalcemia, occurring in up to 25% of patients within 12 months following renal transplantation, and persistent hyperparathyroidism were evaluated following renal transplantation, by retrospective chart review of 1000 adult patients transplanted between January 1, 2003 and January 31, 2008 with at least six months follow-up. Serum calcium, parathyroid hormone, and phosphate levels were recorded at 12, 24, 36, and 48 months. Average follow-up was 766 (535) d (mean (SD); median 668 d). Majority were first transplants (85%); deceased donor 57%. Point prevalence of hypercalcemia (serum Ca(2+) > 2.6 mM) was 16.6% at month 12, 13.6% at month 24, 9.5% at month 36, and 10.1% at month 48. Point prevalence of serum parathyroid hormone (PTH) > 10 pM was 47.6% at month 12, 51.1% at month 24, 43.4% at month 36, and 39.3% at month 48. Estimated glomerular filtration rate (GFR) was maintained throughout and was not different between patients with or without hypercalcemia or elevated PTH. Cinacalcet was prescribed in 12% of patients with hypercalcemia and persistent hyperparathyroidism; parathyroidectomy was performed in 112/1000 patients, 15 post-transplant. Persistent hyperparathyroidism, often accompanied by hypercalcemia, is common following successful renal transplantation, but the lack of clear management suggests the need for further study and development of evidence-based guidelines.

HDAC inhibitor confers radiosensitivity to prostate stem-like cells.

BACKGROUND: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction. METHODS: Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2ß1integrin(hi)/CD133(+)), transit-amplifying (TA, α2ß1integrin(hi)/CD133(-)) and committed basal (CB, α2ß1integrin(lo)) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser. RESULTS: Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation. INTERPRETATION: Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction.

Retinoic acid represses invasion and stem cell phenotype by induction of the metastasis suppressors RARRES1 and LXN.

The mouse haematopoietic stem cell (SC) regulator Latexin (LXN) is the only known homologue of the retinoic acid receptor responder 1 (RARRES1) gene. Both genes lie adjacent on chromosome 3 and differ mostly by the presence of a transmembrane domain in RARRES1. Despite their homology, it is not known whether they possess similar regulatory mechanisms, cellular localization and function. Here, we identified RARRES1 and LXN as highly significantly downregulated genes in human prostate SCs, whose expression was induced by the pro-differentiation agent all-trans retinoic acid (atRA). AtRA induced expression in the most differentiated cells compared with the SC fraction, suggesting that this subpopulation was less responsive to atRA. Small interfering RNA suppression of RARRES1 and LXN enhanced the SC properties of primary prostate cultures, as shown by a significant increase in their colony-forming ability. Expression of both RARRES1 and LXN was co-ordinately repressed by DNA methylation in prostate cancer cell lines and inhibition of RARRES1 and LXN increased the invasive capacity of primary prostate cultures, which also fully rescued an inhibitory effect induced by atRA. Moreover, we showed that RARRES1 and LXN reside within different sub-cellular compartments, providing evidence that RARRES1 is not a plasma membrane protein as previously supposed but is located primarily in the endoplasmic reticulum; whereas LXN was detected in the nucleus of prostate epithelial cells. Thus, LXN and RARRES1 are potential tumour suppressor genes, which are co-ordinately regulated, SC-silenced genes functioning to suppress invasion and colony-forming ability of prostate cancer cells; yet the proteins reside within different sub-cellular compartments.

[Supraglottic airway devices in emergency medicine : impact of gastric drainage]. / Supraglottische Atemwegshilfen in der Notfallmedizin : Stellenwert der Magendrainage.

This case report describes a life-saving use of a supraglottic airway device (LT-D™-Larynxtubus, VBM Medizintechnik, Sulz, Germany) in an out-of-hospital emergency patient suffering from severe traumatic brain injury. Mechanical ventilation with the laryngeal tube was complicated by repeated airway obstructions and pronounced gastric distension with air as a consequence of oropharyngeal leakage. In this situation pulmonary ventilation of the patient was compromised so that emergency endotracheal intubation became necessary in the resuscitation area with vital indications. In this context the status of supraglottic airway devices in emergency medicine is discussed as well as the reasons for the gastric distension. Besides the immediate drastic consequences of gastric distension with respect to pulmonary ventilation, potential deleterious non-pulmonary consequences of this complication are highlighted. The clinical relevance of the described complications as well as the associated possibility of an optimized position control necessitate the recommendation only to use second generation supraglottic airway devices with integrated gastric access in (out-of-hospital) emergency medicine.

Assessment of a preclinical model for studying the survival and engraftment of human stem cell derived osteogenic cell populations following orthotopic implantation.

INTRODUCTION: Preclinical studies with osteoprogenitor cells derived from human embryonic stem cells (hESC) do not lead to substantial bone regeneration in vivo. The degree of survival following implantation might play a role in their long term efficiency. We investigated the initial engraftment of hESCs-derived cells during two weeks post-implantation and compared it to such response for adult bone marrow stromal cells (hBMSC)-derived osteoprogenitor cells. METHODS: hBMSC and H9-hES cells pre-treated with osteogenic factors were implanted into a calvarial defect in both adult WT and nude rats. At days 7 and 14 post-implantation, samples were analysed for persistence of implanted cells, initiation of regeneration of host bone, angiogenesis and apoptosis. RESULTS: At day 7, hESC and hBMSC were detected within defects in both rat strains. By day 14 human cells were only detected in immune-deficient rats whilst still maintaining an osteoblastic phenotype and engendered a significant increase in bone formation. In WT animals, the participation of implanted cells was very limited due to their poor survival. CONCLUSION: This study demonstrates the ability of hESC and hBMSC derived osteoprogenitor cells to survive transplantation, to engraft and to develop an osteogenic phenotype during the early stage following implantation, validating the appropriate preclinical model.

The effect of a cervical collar on the seal pressure of the LMA Supreme™: a prospective, crossover trial.

For personnel inexperienced in airway management, supraglottic airway devices may be the first choice in an emergency. Changing head position is known to reduce the seal pressure of a laryngeal mask airway. The aim of this study was to investigate whether the use of a cervical collar improves the stability of airways secured with the LMA Supreme™ (The Laryngeal Mask Company Limited, Mahé, Seychelles). In this crossover trial, the primary endpoint was the difference in the seal pressure of the LMA Supreme in anaesthetised patients in maximum passive extension of the neck, with and without a cervical collar. The median (IQR [range]) seal pressure was 18 (13.8-22.1 [0-30]) cmH(2) O in maximum passive extension without a cervical collar. With a cervical collar in place, the seal pressure increased to 28 (22.8-30 [17-30]) cmH(2) O (p<0.001). In the neutral head position, the seal pressure was 22 (17.6-24.5 [12-30]) cmH(2) O without and 27 (22-30 [12-30]) cmH(2) O with a cervical collar in place (p<0.001). We found that a cervical collar stabilises the airway with an LMA Supreme in place and we recommend this combination for (pre-hospital) emergency cases.

Polybrominated diphenyl ethers (PBDE) in blood of children in Baden-Württemberg between 2002/03 and 2008/09.

Polybrominated diphenyl ethers (PBDE) are used in high amounts as flame retardants in plastic materials and textiles. Due to their persistence, their accumulation in the food chain and their toxic properties they have been integrated in the human biomonitoring program of the Baden-Württemberg State Health Office since 2002. In repeated cross-sectional studies in winter 2002/03 (n=162), 2004/05 (n=194), 2005/06 (n=411) and 2008/09 (n=770) blood samples of 9-11-year-old pupils were taken, pooled and analysed for PBDE after extraction and purification by silica gel using HRGC/HRMS. Samples were pooled according to region, gender, and breast feeding. PBDE in the pooled samples ranged from 1.9 to 12.5 ng/g blood fat (sum of all PBDE). Mean concentrations of PBDE, calculated for the four investigation periods, were 6.2 ng/g (2002/03), 5.4 ng/g (2004/05), 7.8 ng/g (2005/06) and 6.7 ng/g (2008/09). While the concentration of the decabrominated diphenyl ether (BDE-209) increased, the concentration of other congeners (BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183) decreased slightly or remained at the same level. Consistent differences with respect to gender and breast-feeding were not recognizable. Concentrations of PBDE in children range on the same level as in adults and do not seem to be critical from the toxicological point of view. Because of the slight increase of BDE 209, the internal concentrations of BDE should be monitored in the future. The strong variations in PBDE concentration between the different pooled samples indicate that, apart from ingestion, other routes of exposure (dermal, inhalation) and additional sources (textiles, building materials) must be taken into consideration.

[Continuous local wound infusion with local anesthetics : For thoracotomy and major abdominal interventions]. / Kontinuierliche lokale Wundinfusion mit Lokalanästhetika : Bei Thorakotomien und großen abdominellen Eingriffen.

Wound infusion with local anesthetics is a nearly 100 years old proven and secure analgesic method. Recently special wound infusion catheters have become available which can be placed intraoperatively into the wound under direct supervision of the surgeon to infuse local anesthetics and optimize postoperative analgesia. For thoracotomy this method was modified to improve its efficacy and the catheters are used to establish a continuous paravertebral intercostal nerve block (PVB). Many studies have confirmed the analgesic power of PVB which results in a pain reduction comparable to thoracic epidural analgesia (TEA) but without TEA-specific side-effects, in particular hypotension. The efficacy of continuous local wound infusion (CLWI) is less obvious for laparotomy. If fundamental preconditions for this loco-regional method are considered (indications, choice of catheter, local anesthetic dose) the laparotomy wound could also be suitable for the use of CLWI. According to the literature currently available CLWI is not associated with an increased risk of wound infections.

Blunting of adaptive responses to resistance exercise training in women over 75y.

BACKGROUND: It is unclear how aging affects adaptive responses to resistance exercise training (RET), especially in women. We hypothesized that (i) increases in muscle mass and function after RET would be blunted in older women, and (ii) reduced 'pro-anabolic' changes in gene expression after a single bout of RE may underlie the blunting. METHODS: Muscle biopsies were obtained from 9 older (76-82y) and 16 younger (19-30y) women at rest and 2.5h after RE (6×20 quadriceps maximal voluntary contractions (MVCs)) for measurement of select anabolic (e.g. IGFs, MyoD) and catabolic (e.g. MAFBx, MuRF-1) transcripts by RT-PCR. Thereafter participants undertook a supervised program of RET (4×15 MVCs 3× wk/12wk). We measured knee extensor muscle volume, fatty infiltration, and mechanical muscle quality before and after RET. RESULTS: Before RET, older women were ~30% weaker (MVC 208 vs. 297N) and had ~40% less quadriceps muscle (0.97 vs. 1.54L) with greater fatty infiltration (14% vs. 10%). The most notable difference in mRNA expression after RE was for regulated in development and DNA damage response 1 (REDD1) (an endogenous suppressor of mammalian target of rapamycin (mTOR) signaling), which was depressed (-80%), but only in young women. Moreover, adaptive responses to RET were blunted in older women with respect to increases in muscle volume (+2.5% (old) vs. +6.2% (young)) and strength (+16% (old) vs. +27% (young)). CONCLUSIONS: Adaptations to RET are markedly blunted in older women, perhaps in-part due to the inability to downregulate REDD1 and thus upregulate mTOR signaling after RE.

A prospective study of the factors affecting outcomes of nonsurgical root canal treatment: part 1: periapical health.

AIM: To investigate the probability of and factors influencing periapical status of teeth following primary (1°RCTx) or secondary (2°RCTx) root canal treatment. METHODOLOGY: This prospective study involved annual clinical and radiographic follow-up of 1°RCTx (1170 roots, 702 teeth and 534 patients) or 2°RCTx (1314 roots, 750 teeth and 559 patients) carried out by Endodontic postgraduate students for 2-4 (50%) years. Pre-, intra- and postoperative data were collected prospectively on customized forms. The proportion of roots with complete periapical healing was estimated, and prognostic factors were investigated using multiple logistic regression models. Clustering effects within patients were adjusted in all models using robust standard error. RESULTS: proportion of roots with complete periapical healing after 1°RCTx (83%; 95% CI: 81%, 85%) or 2°RCTx (80%; 95% CI: 78%, 82%) were similar. Eleven prognostic factors were identified. The conditions that were found to improve periapical healing significantly were: the preoperative absence of a periapical lesion (P = 0.003); in presence of a periapical lesion, the smaller its size (P ≤ 0.001), the better the treatment prognosis; the absence of a preoperative sinus tract (P = 0.001); achievement of patency at the canal terminus (P = 0.001); extension of canal cleaning as close as possible to its apical terminus (P = 0.001); the use of ethylene-diamine-tetra-acetic acid (EDTA) solution as a penultimate wash followed by final rinse with NaOCl solution in 2°RCTx cases (P = 0.002); abstaining from using 2% chlorexidine as an adjunct irrigant to NaOCl solution (P = 0.01); absence of tooth/root perforation (P = 0.06); absence of interappointment flare-up (pain or swelling) (P =0.002); absence of root-filling extrusion (P ≤ 0.001); and presence of a satisfactory coronal restoration (P ≤ 0.001). CONCLUSIONS: Success based on periapical health associated with roots following 1°RCTx (83%) or 2°RCTx (80%) was similar, with 10 factors having a common effect on both, whilst the 11th factor 'EDTA as an additional irrigant' had different effects on the two treatments.

A prospective study of the factors affecting outcomes of non-surgical root canal treatment: part 2: tooth survival.

AIM: To investigate the probability of and factors influencing tooth survival following primary (1°RCTx) or secondary (2°RCTx) root canal treatment. METHODOLOGY: This prospective study involved annual follow-up of 2 (100%) to 4 years (50%) of 1°RCTx (759 teeth, 572 patients) and 2°RCTx (858 teeth, 642 patients) carried out by Endodontic postgraduate students. Pre-, intra- and post-operative data were collected prospectively from consented patients. Information about extraction of the root filled tooth was sought from the patient, the referring dentist or derived from the patient's records and included the timing and reasons for extraction. Tooth survival was estimated and prognostic factors were investigated using Cox regression. Clustering effects within patients were adjusted in all models using robust standard error. RESULTS: The 4-year cumulative tooth survival following 1°RCTx [95.4% (93.6%, 96.8%)] or 2°RCTx [95.3% (93.6%, 96.5%)] was similar. Thirteen prognostic factors were identified. Significant patient factors included history of diabetes and systemic steroid therapy. Significant pre-operative factors included narrow but deep periodontal probing depth; pain; discharging sinus; and iatrogenic perforation (for 2°RCTx cases only). Significant intra-operative factors included iatrogenic perforation; patency at apical terminus; and extrusion of root fillings. Significant post-operative restorative factors included presence of cast restoration versus temporary restoration; presence of cast post and core; proximal contacts with both mesial and distal adjacent teeth; and terminal location of the tooth. The presence of pre-operative pain had a profound effect on tooth loss within the first 22 months after treatment [hazard ratio (HR) = 3.1; P = 0.001] with a lesser effect beyond 22 months (HR = 2.4; P = 0.01). Patency at the apical terminus reduced tooth loss (HR = 0.3; P < 0.01) within the first 22 months after treatment but had no significant effect on tooth survival beyond 22 months. Extrusion of gutta-percha root filling did not have any effect on tooth survival (HR = 1.1; P = 0.2) within the first 22 months but significantly increased the hazard of tooth loss beyond 22 months (HR = 3.0; P = 0.003). CONCLUSIONS: The 4-year tooth survival following primary or secondary root canal treatment was 95%, with thirteen prognostic factors common to both.

[Treatment of polytrauma in the intensive care unit]. / Polytraumaversorgung auf der Intensivstation.

The treatment of severely injured trauma patients (polytrauma) is one of the outstanding challenges in medical care. Early in the initial course the patient's diagnostics have to be scrupulously reevaluated by an interdisciplinary team (tertiary trauma survey) to reduce deleterious sequelae of missed injuries after the initial assessment. Severely injured patients stay in intensive care for an average of 11 days. During this time the patient's therapy has to ensure a high quality evidence-based intensive care treatment and simultaneously has to be tailored to the current individual injuries. Because of the fact that the damage control strategy is gaining increasing acceptance, the intensive care unit plays a pivotal role in the critical time between emergency and elective surgery. Therefore a close cooperation between physicians of the intensive care unit and all surgical disciplines involved is essential to reach the aim of therapeutic efforts. After survival of emergency treatment patients with severe trauma should be reintegrated into social and occupational life as soon as possible.

Tooth survival following non-surgical root canal treatment: a systematic review of the literature.

AIMS: To investigate (i) the effect of study characteristics on reported tooth survival after root canal treatment (RCTx) and (ii) the effect of clinical factors on the proportion of root filled teeth surviving after RCTx. METHODOLOGY: Longitudinal human clinical studies investigating tooth survival after RCTx which were published up to the end of 2007 were identified electronically (MEDLINE and Cochrane database 1966-2007 December, week 4). In addition, four journals (Dental Traumatology, International Endodontic Journal, Journal of Endodontics, Oral Surgery Oral Medicine Oral Pathology Oral Radiology & Endodontics), bibliographies of all relevant articles and review articles were hand searched. Two reviewers (Y-LN, KG) assessed and selected the studies based on specified inclusion criteria and extracted the data onto a pre-designed proforma, independently. The criteria were as follows: (i) clinical study on RCTx; (ii) stratified analysis of primary and secondary RCTx available; (iii) sample size given and larger than 10; (iv) at least 6-month postoperative review; (v) success based on survival of tooth; and (vi) proportion of teeth surviving after treatment given or could be calculated from the raw data. Three strands of evidence or analyses were used to triangulate a consensus view. The reported findings from individual studies, including those excluded for quantitative analysis, were utilized for the intuitive synthesis, which constituted the first strand of evidence. Secondly, the pooled weighted proportion of teeth surviving and thirdly the combined effects of potential prognostic factors were estimated using the fixed and random effects meta-analyses on studies fulfilling all the inclusion criteria. RESULTS: Of the 31 articles identified, 14 studies published between 1993 and 2007 were included. The majority of studies were retrospective (n = 10) and only four prospective. The pooled percentages of reported tooth survival over 2-3, 4-5 and 8-10 years following RCTx were 86% (95% CI: 75%, 98%), 93% (95% CI: 92%, 94%) and 87% (95% CI: 82%, 92%), respectively. Substantial differences in study characteristics were found to hinder effective direct comparison of findings. Evidence for the effect of prognostic factors on tooth survival was weak. Based on the data available for meta-analyses, four conditions were found to significantly improve tooth survival. In descending order of influence, the conditions increasing observed proportion of survival were as follows: (i) a crown restoration after RCTx; (ii) tooth having both mesial and distal proximal contacts; (iii) tooth not functioning as an abutment for removable or fixed prosthesis; and (iv) tooth type or specifically non-molar teeth. Statistical heterogeneity was substantial in some cases but its source could not be investigated because of insufficient available information. CONCLUSIONS: The pooled proportion of teeth surviving over 2-10 years following RCTx ranged between 86% and 93%. Four factors (listed above) were identified as significant prognostic factors with concurrence between all three strands of evidence.