Critical incident reporting over time: a retrospective, descriptive analysis of 5493 cases.

PURPOSE: As recommended by the WHO and many national healthcare authorities, health care institutions of most industrialised countries have employed a critical incident reporting system (CIRS). However, little is known about differences in critical incidents across clinical specialties, the use of CIRSs amongst different professional groups, the types, severity and risk of reoccurrence of critical incidents, their contributing factors and the preventive actions taken in response. METHODS: In this retrospective, descriptive study we critically reviewed all reports filed in the CIRS of our institution between 2013 and 2019 and analysed characteristics over time. RESULTS: Of the 5493 analysed incidents, the main types were related to medications (32.8%), clinical procedures (32.6%) or behaviour of employees (23.3%). Only 21.6% of reports were made by physicians, 51.3% were rated at least "high risk". Major contributing factors were personal factors (44.0%), lack of training and knowledge (43.7%) and communication errors (36.1%). Most actions taken to prevent similar events aimed at improving communications (23.6%); in 46.3% no actions whatsoever were taken. Longitudinal analysis revealed that reporting increased in internal medicine and obstetrics but collapsed in laboratory medicine / microbiology. Steady increases in medication-type incidents as well as lack of training and knowledge as contributing factors were observed. CONCLUSION: This study revealed that the efferent loop (feedback, preventive actions taken) was the weakest part of the CIRS in our institution, indicating that no learning may have resulted from a large number of reports. In particular, the actions taken appeared to not adequately address the major contributing factors. This highlights that special attention must be paid to the efferent loop of a CIRS to fulfil the purpose of such a reporting system and ultimately to improve patient safety.

Disentangling multiple chemical and non-chemical stressors in a lotic ecosystem using a longitudinal approach.

Meeting ecological and water quality standards in lotic ecosystems is often failed due to multiple stressors. However, disentangling stressor effects and identifying relevant stressor-effect-relationships in complex environmental settings remain major challenges. By combining state-of-the-art methods from ecotoxicology and aquatic ecosystem analysis, we aimed here to disentangle the effects of multiple chemical and non-chemical stressors along a longitudinal land use gradient in a third-order river in Germany. We distinguished and evaluated four dominant stressor categories along this gradient: (1) Hydromorphological alterations: Flow diversity and substrate diversity correlated with the EU-Water Framework Directive based indicators for the quality element macroinvertebrates, which deteriorated at the transition from near-natural reference sites to urban sites. (2) Elevated nutrient levels and eutrophication: Low to moderate nutrient concentrations together with complete canopy cover at the reference sites correlated with low densities of benthic algae (biofilms). We found no more systematic relation of algal density with nutrient concentrations at the downstream sites, suggesting that limiting concentrations are exceeded already at moderate nutrient concentrations and reduced shading by riparian vegetation. (3) Elevated organic matter levels: Wastewater treatment plants (WWTP) and stormwater drainage systems were the primary sources of bioavailable dissolved organic carbon. Consequently, planktonic bacterial production and especially extracellular enzyme activity increased downstream of those effluents showing local peaks. (4) Micropollutants and toxicity-related stress: WWTPs were the predominant source of toxic stress, resulting in a rapid increase of the toxicity for invertebrates and algae with only one order of magnitude below the acute toxic levels. This toxicity correlates negatively with the contribution of invertebrate species being sensitive towards pesticides (SPEARpesticides index), probably contributing to the loss of biodiversity recorded in response to WWTP effluents. Our longitudinal approach highlights the potential of coordinated community efforts in supplementing established monitoring methods to tackle the complex phenomenon of multiple stress.

Possible advantages of early stabilization of spinal fractures in multiply injured patients with leading thoracic trauma - analysis based on the TraumaRegister DGU®.

BACKGROUND: Major trauma often comprises fractures of the thoracolumbar spine and these are often accompanied by relevant thoracic trauma. Major complications can be ascribed to substantial simultaneous trauma to the chest and concomitant immobilization due to spinal instability, pain or neurological dysfunction, impairing the respiratory system individually and together. Thus, we proposed that an early stabilization of thoracolumbar spine fractures will result in significant benefits regarding respiratory organ function, multiple organ failure and length of ICU / hospital stay. METHODS: Patients documented in the TraumaRegister DGU®, aged ≥16 years, ISS ≥ 16, AISThorax ≥ 3 with a concomitant thoracic and / or lumbar spine injury severity (AISSpine) ≥ 3 were analyzed. Penetrating injuries and severe injuries to head, abdomen or extremities (AIS ≥ 3) led to patient exclusion. Groups with fractures of the lumbar (LS) or thoracic spine (TS) were formed according to the severity of spinal trauma (AISspine): AISLS = 3, AISLS = 4-5, AISTS = 3 and AISTS = 4-5, respectively. RESULTS: 1740 patients remained for analysis, with 1338 (76.9%) undergoing spinal surgery within their hospital stay. 976 (72.9%) had spine surgery within the first 72 h, 362 (27.1%) later on. Patients with injuries to the thoracic spine (AISTS = 3) or lumbar spine (AISLS = 3) significantly benefit from early surgical intervention concerning ventilation time (AISLS = 3 only), ARDS, multiple organ failure, sepsis rate (AISTS = 3 only), length of stay in the intensive care unit and length of hospital stay. In multiple injured patients with at least severe thoracic spine trauma (AISTS ≥ 4) early surgery showed a significantly shorter ventilation time, decreased sepsis rate as well as shorter time spend in the ICU and in hospital. CONCLUSIONS: Multiply injured patients with at least serious thoracic trauma (AISThorax ≥ 3) and accompanying spine trauma can significantly benefit from early spine stabilization within the first 72 h after hospital admission. Based on the presented data, primary spine surgery within 72 h for fracture stabilization in multiply injured patients with leading thoracic trauma, especially in patients suffering from fractures of the thoracic spine, seems to be beneficial.

Spatial patterns of water quality impairments from point source nutrient loads in Germany's largest national River Basin (Weser River).

We employed the well-established Horton-Strahler, hierarchical, stream-order (ω) scheme to investigate scaling of nutrient loads (P and N) from ~845 wastewater treatment plants (WWTPs) distributed along the river network in urbanized Weser River, the largest national basin in Germany (~46K km2; ~8.4 million population). We estimated hydrologic and water quality impacts at the reach- and basin-scales, at two steady river discharge conditions (median flow, QR50; low-flow, QR90). Of the five WWTPs class-sizes (1 ≤ k ≤ 5), ~68% discharge to small low-order streams (ω < 3). We found large variations in capacity to dilute WWTP nutrient loads because of variability in (1) treated wastewater discharge (QU) within and among different class-sizes, and (2) river discharge (QR) within low-order streams (ω < 3) resulting from differences in drainage areas. For QR50, reach-scale water quality impairment assessed by nutrient concentration was likely at 136 (~16%) locations for P and 15 locations (~2%) for N. About 90% of these locations were lower-order streams (ω < 3). At QR50 and only with dilution, basin-scale cumulative nutrient loads from multiple upstream WWTPs increase impaired locations to 266 (~32% of total) for P. Considering in-stream uptake decreased P-impaired streams to 225 (~27%), suggesting the dominant role of dilution in the Weser River basin. Role of in-stream uptake diminished along the flow paths, while dilution in larger streams (4 ≤ ω ≤ 7) minimizes the impact of WWTP loads. Under QR90 conditions [(QR50/QR90) ~ 2.5], water quality impaired locations will likely double for the basin-scale analyses. Long-term water quality data suggested that diffuse sources are the primary contributors for water quality impairments in large streams. Our data-modeling synthesis approach is transferable to other urbanized river basins and extends understanding of point source impacts on water quality across spatial scales.

Longitudinal patterns and response lengths of algae in riverine ecosystems: A model analysis emphasising benthic-pelagic interactions.

In riverine ecosystems primary production is principally possible in two habitats: in the benthic layer by sessile algae and in the surface water by planktonic algae being transported downstream. The relevance of these two habitats generally changes along the rivers' continuum. However, analyses of the interaction of algae in these two habitats and their controlling factors in riverine ecosystems are, so far, very rare. We use a simplified advection-diffusion model system combined with ecological process kinetics to analyse the interaction of benthic and planktonic algae and nutrients along idealised streams and rivers at regional to large scales. Because many of the underlying processes affecting algal dynamics are influenced by depth, we focus particularly on the impact of river depth on this interaction. At constant environmental conditions all state variables approach stable spatial equilibria along the river, independent of the boundary conditions at the upstream end. Because our model is very robust against changes of turbulent diffusion and stream velocity, these spatial equilibria can be analysed by a simplified ordinary differential equation (ode) version of our model. This model variant reveals that at shallower river depths, phytoplankton can exist only when it is subsidised by detaching benthic algae, and in turn, at deeper river depths, benthic algae can exist only in low biomasses which are subsidised by sinking planktonic algae. We generalise the spatial dynamics of the model system using different conditions at the upstream end of the model, which mimic various natural or anthropogenic factors (pristine source, dam, inflow of a waste water treatment plant, and dilution from e.g. a tributary) and analyse how these scenarios influence different aspects of the longitudinal spatial dynamics of the full spatial model: the relation of spatial equilibrium to spatial maximum, the distance to the spatial maximum, and the response length. Generally, our results imply that shallow systems recover within significantly shorter distances from spatially distinct disturbances when compared to deep systems, independent of the type of disturbance.

Predictors of postoperative hemoglobin drop after laparoscopic myomectomy.

INTRODUCTION: Laparoscopic myomectomy (LM) can be associated with significant bleeding. AIM: To identify factors influencing the postoperative hemoglobin (Hb) drop after LM. MATERIAL AND METHODS: This is a retrospective, single-center study. We evaluated data of 150 consecutive patients undergoing LM due to intramural myomas between 2010 and 2015. RESULTS: The median age of the patients was 37 (23-53) years. The mean diameter of the largest myoma was 5.7 ±2.3 (1.5-12) cm. The mean surgical time was 83 ±38 (35-299) min. The median number of sutures was 3 (1-11). The mean postoperative Hb drop was 1.6 ±1.2 (0-6) g/dl, and the mean estimated blood loss was 261 ±159 (50-1700) ml. In the univariate analysis, the postoperative Hb drop correlated with the duration of surgery (p < 0.001), diameter of the largest myoma (p < 0.001), cumulative myoma weight (p < 0.001), and number of sutures (p < 0.001), but not with patients' age or number of intramural myomas. In the multivariable analysis, the surgical time (ß = 0.395, p < 0.001), diameter of the largest myoma (ß = 0.292, p = 0.03) and preoperative Hb concentration (ß = 0.299, p < 0.001) predicted the postoperative Hb change. CONCLUSIONS: Surgical time and dominant myoma diameter are independent predictors of the postoperative Hb drop after LM.

Improvement of Perioperative Outcomes in Major Gynecological and Gynecologic-Oncological Surgery with Hemostatic Gelatin-Thrombin Matrix.

AIM: To assess the impact of the use of intraoperative hemostatic gelatin-thrombin matrix (HM) (Floseal®, Baxter Healthcare) on transfusion rates and short-term perioperative outcomes in gynecological surgery. PATIENTS AND METHODS: In this retrospective, single-center study, we evaluated data of 215 patients (83 cases and 132 controls) undergoing extensive gynecological surgery (e.g. oncological procedures) with and without intraoperative HM application. RESULTS: Cases and controls did not differ according to age, preoperative hemoglobin (Hb) concentration, and Hb or C-reactive protein (CRP) levels at discharge. Patients receiving HM had significantly reduced operative (168 vs. 199 min, p=0.02) and hospitalization (9 vs. 14 days, p<0.001) times. The mean postoperative Hb drop (3.33 vs. 4.51 g/dl, p<0.001), and the mean postoperative increase in CRP (94.9 vs. 149.1 mg/l, p<0.001) were significantly less pronounced within the HM group. Despite more prevalent coagulopathy (48 vs. 31%, p=0.02), e.g. due to anticoagulant use (15.7 vs. 3%, p<0.001), patients treated using HM needed less frequent transfusions of packed red blood cells [odds ratio (OR)= 0.13, 95% confidence interval (CI)=0.07-0.24) and fresh frozen plasma (OR=0.51, 95% CI=0.24-1.05). In comparison to controls, the need for surgical revisions (OR 0.1, CI 95% 0.02-0.42) and intensive-care unit admissions (OR 0.15, 95% CI=0.08-0.30) was lower in patients treated with HM. CONCLUSION: To our knowledge, our study is the largest case-control study focusing on Floseal® use in gynecology. The use of HM was associated with significantly better short-term perioperative outcomes. Due to its local action, HM seems to be particularly useful in patients in which anticoagulant medication cannot be paused.

Can nutrient pathways and biotic interactions control eutrophication in riverine ecosystems? Evidence from a model driven mesocosm experiment.

Ecological theory predicts that the relative importance of benthic to planktonic primary production usually changes along the rivers' continuum from a predomination of benthic algae in lower stream orders to a predomination of planktonic algae at higher orders. Underlying mechanisms driving the interaction between algae in these habitats, its controlling factors and consequences for riverine ecosystems are, however, only partly understood. We present a mechanistic analysis of the governing ecological processes using a simplified, numerical model and examine how abiotic factors and biotic interactions influence benthic and planktonic algae by changing resource competition. We compare the outcome of the model with the results of a factorial mesocosm experiment mimicking the parameter spaces of the model. The results show a remarkable similarity with regard to the temporal development of benthic and pelagic algal biomass and shifting dominance patterns. In particular we analyse the effects of the pathways of nutrient supply (upwelling from the hyporheic zone, direct supply to the surface water, or via both pathways) and grazing in a gradient of river depths. Our results show that detachment of benthic algae, sinking of planktonic algae and the pathway of nutrient supply are key processes determining the respective algal biomass distributions particularly in shallow and intermediate deep systems. Increasing nutrient supply increases algal biomasses, but does not change the general pattern of the interactions. Decreasing light supply decreases the dominance of planktonic algae, but increases dissolved nutrients. At intermediate to high grazing rates algal biomass can be controlled by grazers, but however, at high grazing rates, dissolved nutrients accumulate in the surface water. Our results indicate that nutrient pathways, resource competition and internal control by grazing need to be considered explicitly for the understanding and explanation of eutrophication phenomena in riverine ecosystems. As a consequence, ecologically effective eutrophication management of running water systems has to go beyond the control of nutrient emissions or the achievement of limiting threshold values in the receiving waters, but requires the consideration of the nutrient pathways (surface water versus groundwater) and the shifting biological controls from lower to higher order stream ecosystems.

Uterine rupture after balloon inflation of the intrauterine Foley catheter during laparoscopic chromopertubation.

Laparoscopic chromopertubation is considered "gold standard" for checking the tubal patency. Foley catheter is frequently used for blue dye during chromopertubation. Complications associated with the intra-uterine use of Foley catheter are infrequent. The mean normal capacity of the uterine cavity is about 9 ml, and an inflation of up to 30 ml (e. g. during thermal balloon ablation procedures) is considered safe. We report a uterine rupture in a 36-year-old woman undergoing laparoscopic chromopertubation due to primary infertility. Thirteen years ago, the patient had three consecutive laparotomies because of appendicitis, peritonitis and retroperitoneal abscess. For the present laparoscopy, the Foley catheter (Nelaton, charier 10, balloon 5 ml) was used. The first blocking of the balloon with 3.5 ml saline was insufficient; however after inflating with 5 ml, a rupture of the uterine fundus occurred. The balloon remained intact and both tubes appeared patent. The myometrium was sutured and the postoperative course was uneventful. We presume that-in the present case-the expansive capacity of the uterine wall may have been reduced after the series of severe pelvic inflammations. Nevertheless, if using a Foley catheter for the chromopertubation, the optimal pressure for its intrauterine fixation needs still to be determined.

Usefulness of the preoperative platelet count in the diagnosis of adnexal tumors.

Platelets seem to play a role in the development of ovarian cancer. Platelet count (PLT) is an ubiquitous available parameter. We analyzed retrospectively data of 756 patients with primary adnexal tumors: 584 benign and 172 malignant (148 invasive and 24 borderline) cases. We compared the diagnostic accuracy of CA125, PLT, and a combination of CA125 and PLT. The cutoff values for CA125 and PLT were 35 U/ml and 350/nl, respectively. The median age of patients with benign and malignant tumors was 45 and 64 years, respectively. A total of 77/172 (44.8 %) malignant and 50/584 (8.6 %) benign cases presented with thrombocytosis (PLT ≥350/nl). The median PLT differed between benign and malignant cases (257/nl vs. 330/nl; p < 0.001), similarly as CA125 did (17 vs. 371 U/ml; p < 0.001). In the multivariate analysis, age, CA125, and thrombocytosis predicted independently the presence of malignancy. The results of CA125 were false positive in 21 % and false negative in 13 %. If considered together, thrombocytosis + CA125 were false positive only in 9 %, whereas the false negative rate was 12 %. The sensitivity and specificity of CA125, thrombocytosis, and thrombocytosis + CA125 for detecting adnexal malignancy were 0.88/0.78, 0.45/0.91, and 0.81/0.94, respectively. The positive predictive value (PPV) of CA125, thrombocytosis, and thrombocytosis + CA125 was 0.79, 0.61, and 0.91, respectively. In conclusion, PLT is an ubiquitously available parameter that could be useful in the diagnostic evaluation of pelvic mass. Considering thrombocytosis additionally to CA125 improves the specificity and PPV and reduces the false positive rate in detecting adnexal malignancy.

Hysteroscopic treatment of uterine tumor resembling ovarian sex cord-like tumor (UTROSCT).

The decision to preserve the uterus in a young nulliparous woman with an extremely rare tumor is challenging. Uterine tumor resembling ovarian sex cord-like tumor (UTROSCT) belongs to the rarest uterine pathologies. A 22-year-old nulligravida with uterine bleeding underwent a hysteroscopic resection of an intrauterine mass presumed as grade-1 submucous myoma. According to the presence of sex cord-like differentiation and positivity for calretinin, CD99, estrogen receptor, vimentin, WT1 and Melan-A, the tumor was diagnosed as UTROSCT. After 28 months, without any adjuvant therapy, the patient is still free of recurrence. This is the youngest patient with UTROSCT reported so far, with the longest follow-up among all five cases treated via hysteroscopy. Although UTROSCT has been traditionally treated with hysterectomy (with or without bilateral salpingo-oophorectomy), no established treatment protocol for UTROSCT exists. UTROSCT shows a low-malignant potential, but metastasizing and recurrent cases occur. In light of the probably less aggressive tumor biology and with respect to the patient's autonomy, a conservative, uterus preserving treatment appears to be justified in selected cases in which close follow-up can be guaranteed. Further case reports are needed to prove the safety of organ-preserving strategy in UTROSCT.

Anaplastic pelvic carcinoma secondary to low-grade endometrial carcinoma.

BACKGROUND: Low-grade endometrial carcinoma has an excellent prognosis. The risk of secondary cancer after endometrial carcinoma is moderately increased and is mostly related to the field of postoperative radiation (small intestine, colon, vagina, and urinary bladder). Anaplastic (undifferentiated) pelvic carcinoma (APC) is rare and probably under-reported. To date, only one publication has reported six cases of APC that were secondary to low-grade endometrial carcinoma. CASE REPORT: We have analyzed the fulminant course of APC-preceded by paraneoplastic arthritis-four months after hysterectomy and adnexectomy for low-grade endometrial carcinoma (endometrioid type, moderately differentiated, tumor diameter: 2 cm, infiltration depth 3 of 15 mm). The 73-year-old patient died five weeks after the diagnosis of the second malignancy. CONCLUSION: The prognosis of APC is poor and the limitations of the therapy result from aggressive tumor biology and rapid deterioration of the patients' general condition. Rheumatological symptoms can precede cancer diagnosis. Immunohistochemistry facilitates the differentiation between primary and secondary carcinoma.

Hymenal anomalies in twins--review of the literature and case report.

UNLABELLED: Subocclusive hymenal variants, such as microperforate or septate hymen, impair somatic functions (e.g., vaginal intercourse or menstrual hygiene) and can negatively impact the quality of life of young women. We know little about the prevalence and inheritance of subocclusive hymenal variants. So far, eight cases of familial occurrence of occlusive hymenal anomalies (imperforate hymen) have been reported. In one of these cases, monozygotic twins were affected. We are reporting the first case of subocclusive hymenal variants (microperforate hymen and septate hymen) in 16-year-old white dizygotic twins. In addition, we review and discuss the current evidence. CONCLUSION: The mode of inheritance of hymenal variants has not been determined so far. Because surgical corrections of hymenal variants should be carried out in asymptomatic patients (before menarche), gynecologists and pediatricians should keep in mind that familial occurrences may occur.

Biogeochemical patterns in a river network along a land use gradient.

The Bode catchment (Germany) shows strong land use gradients from forested parts of the National Park (23% of total land cover) to agricultural (70%) and urbanised areas (7%). It is part of the Terrestrial Environmental Observatories of the German Helmholtz association. We performed a biogeochemical analysis of the entire river network. Surface water was sampled at 21 headwaters and at ten downstream sites, before (in early spring) and during the growing season (in late summer). Many parameters showed lower concentrations in headwaters than in downstream reaches, among them nutrients (ammonium, nitrate and phosphorus), dissolved copper and seston dry mass. Nitrate and phosphorus concentrations were positively related to the proportion of agricultural area within the catchment. Punctual anthropogenic loads affected some parameters such as chloride and arsenic. Chlorophyll a concentration and total phosphorus in surface waters were positively related. The concentration of dissolved organic carbon (DOC) was higher in summer than in spring, whereas the molecular size of DOC was lower in summer. The specific UV absorption at 254 nm, indicating the content of humic substances, was higher in headwaters than in downstream reaches and was positively related to the proportion of forest within the catchment. CO2 oversaturation of the water was higher downstream compared with headwaters and was higher in summer than in spring. It was correlated negatively with oxygen saturation and positively with DOC concentration but negatively with DOC quality (molecular size and humic content). A principle component analysis clearly separated the effects of site (44%) and season (15%), demonstrating the strong effect of land use on biogeochemical parameters.

Papillary-serous adenocarcinoma of the uterine cervix during tamoxifen therapy after bilateral breast cancer.

BACKGROUND: Papillary-serous adenocarcinoma (PSCC) is a very rare subtype of cervical cancer. To our knowledge, this is the first report on PSCC of the uterine cervix following bilateral breast cancer. CASE REPORT: A 61-year-old Caucasian woman underwent conserving surgery of both breasts at the age of 57 years, because of bilateral invasive ductal carcinoma. Radiation and tamoxifen treatment followed. Routine surveillance examinations, including pelvic examination, Papanicolaou (Pap) smear, and transvaginal ultrasound, were uneventful. Recently, a small contact-bleeding mass of the cervix was found. The Pap smear was II (reactive); HPV-DNA test was negative. The biopsy of the mass revealed PSCC with a high expression of p53, carcinoembryonic antigen (CEA), and Ki67 (50%). Staining for estrogen receptor (ER), progesterone receptor (PR), and vimentin was negative. The serum carbohydrate antigen 125 (CA-125) reached 159 U/ml. The patient was treated with radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy. A poorly-differentiated papillary-serous, non-secretory adenocarcinoma, pT1b1, pN0 (0/44), pM0, G3, R0, V0, L0, was confirmed. According to the German recommendations for early-stage cervical cancer, the patient received no adjuvant treatment. Currently, the patient is free of relapse 38 months after the diagnosis of cervical cancer and 87 months after that of breast cancer. CONCLUSION: Immunohistochemistry is helpful in diagnosing rare entities. This case adds further evidence that the prognosis for early-stage PSCC is probably not poorer than that for other cervical adenocarcinomas.

Neuroendocrine carcinoma of the breast--diagnostic and clinical implications.

BACKGROUND: Neuroendocrine breast carcinomas (NEC) are rare. Carcinomas with mixed composition often behave differently from 'pure' histological types, and the prognosis is determined by the proportion of the more aggressive tumour. The molecular classification helps in making therapeutic decisions. CASE REPORT: A 56-year-old Caucasian woman with palpable and preoperatively biopsied breast tumour was treated with breast-conserving surgery. The histological specimen revealed a 17-mm invasive carcinoma with an equal proportion of neuroendocrine and invasive-ductal differentiation, accompanied by peritumoural ductal carcinoma in situ. TNM classification was pT1c(is), pN0 (0/1sn), G3, L0, V0, Pn0, R0. The diagnosis was enhanced by immunohistochemistry: high positivity for synaptophysin, neuron-specific enolase (NSE), neural cell adhesion molecule (CD56), Ki-67 (proliferation index 46%), estrogen receptor (ER) and progesterone receptor (PR), negative for Her-2-neu and cytokeratin 5/6, resulting in diagnosis of the molecular 'luminal B' subtype. Radiation and adjuvant chemotherapy with six cycles of 5-fluorouracil, epirubicin and cyclophosphamide, followed by tamoxifen and subsequent exemestane for five years, were recommended. CONCLUSION: Immunohistochemistry plays a crucial role in the diagnosis of rare cancer subtypes. NEC is characterized by high biological aggressiveness. Molecular classification facilitates therapeutic decisions.

Physical determinants of phytoplankton production, algal stoichiometry, and vertical nutrient fluxes.

Most phytoplankters face opposing vertical gradients in light versus nutrient supplies but have limited capacities for vertical habitat choice. We therefore explored a dynamical model of negatively buoyant algae inhabiting a one-dimensional water column to ask how water column depth and turbulence constrain total (areal) phytoplankton biomass. We show that the population persistence boundaries in water column depth-turbulence space are set by sinking losses and light limitation but that nutrients are most limiting to total biomass in water columns that are neither too shallow or too weakly mixed (where sinking losses prevail) nor too deep and turbulent (where light limitation prevails). In shallow waters, the most strongly limiting process is nutrient influx to the bottom of the water column (e.g., from sediments). In deep waters, the most strongly limiting process is turbulent upward transport of nutrients to the photic zone. Consequently, the highest total biomasses are attained in turbulent waters at intermediate water column depths and in deep waters at intermediate turbulences. These patterns are insensitive to the assumption of fixed versus flexible algal carbon-to-nutrient stoichiometry, and they arise irrespective of whether the water column is a surface layer above a deep water compartment or has direct contact with sediments.

Phytomedicines prepared from Arnica flowers inhibit the transcription factors AP-1 and NF-kappaB and modulate the activity of MMP1 and MMP13 in human and bovine chondrocytes.

Arnica preparations have long been used for the symptomatic treatment of rheumatic complaints and recent clinical trials have demonstrated the beneficial effects of Arnica preparations in the treatment of osteoarthritis (OA). The efficacy of Arnica is presumed to be mainly due to its anti-inflammatory properties and inhibition of the transcription factor NF-kappaB. Here we provide further insights into its molecular mode of action. Arnica preparations suppress MMP1 and MMP13 mRNA levels in bovine and human articular chondrocytes in a concentration-dependent manner and in a low concentration range. This suppression may be due to inhibition of DNA binding of the transcription factors AP-1 and NF-kappaB. Interestingly, sesquiterpene lactones present in the preparations were always more active than the pure compounds, demonstrating the advantage of using plant preparations.

Transient dynamics of pelagic producer-grazer systems in a gradient of nutrients and mixing depths.

Phytoplankton-grazer dynamics are often characterized by long transients relative to the length of the growing season. Using a phytoplankton-grazer model parameterized for Daphnia pulex with either flexible or fixed algal carbon:nutrient stoichiometry, we explored how nutrient and light supply (the latter by varying depth of the mixed water column) affect the transient dynamics of the system starting from low densities. The system goes through an initial oscillation across nearly the entire light-nutrient supply space. With flexible (but not with fixed) algal stoichiometry, duration of the initial algal peak, timing and duration of the subsequent grazer peak, and timing of the algal minimum are consistently accelerated by nutrient enrichment but decelerated by light enrichment (decreasing mixing depth) over the range of intermediate to shallow mixing depths. These contrasting effects of nutrient vs. light enrichment are consequences of their opposing influences on food quality (algal nutrient content): algal productivity and food quality are positively related along a nutrient gradient but inversely related along a light gradient. Light enrichment therefore slows down grazer growth relative to algal growth, decelerating oscillatory dynamics; nutrient enrichment has opposite effects. We manipulated nutrient supply and mixing depth in a field enclosure experiment. The experimental results were qualitatively much more consistent with the flexible than with the fixed stoichiometry model. Nutrient enrichment increased Daphnia peak biomass, decreased algal minimum biomass, decreased the seston C:P ratio, and accelerated transient oscillatory dynamics. Light enrichment (decreasing mixing depth) produced the opposite patterns, except that Daphnia peak biomass increased monotonously with light enrichment, too. Thus, while the model predicts the possibility of the "paradox of energy enrichment" (a decrease in grazer biomass with light enrichment) at high light and low nutrient supply, this phenomenon did not occur in our experiment.

Water temperature and mixing depth affect timing and magnitude of events during spring succession of the plankton.

In many lakes, the most conspicuous seasonal events are the phytoplankton spring bloom and the subsequent clear-water phase, a period of low-phytoplankton biomass that is frequently caused by mesozooplankton (Daphnia) grazing. In Central European lakes, the timing of the clear-water phase is linked to large-scale climatic forcing, with warmer winters being followed by an earlier onset of the clear-water phase. Mild winters may favour an early build-up of Daphnia populations, both directly through increased surface temperatures and indirectly by reducing light limitation and enhancing algal production, all being a consequence of earlier thermal stratification. We conducted a field experiment to disentangle the separate impacts of stratification depth (affecting light supply) and temperature on the magnitude and timing of successional events in the plankton. We followed the dynamics of the phytoplankton spring bloom, the clear-water phase and the spring peak in Daphnia abundance in response to our experimental manipulations. Deeper mixing delayed the timing of all spring seasonal events and reduced the magnitudes of the phytoplankton bloom and the subsequent Daphnia peak. Colder temperatures retarded the timing of the clear-water phase and the subsequent Daphnia peak, whereas the timing of the phytoplankton peak was unrelated to temperature. Most effects of mixing depth (light) and temperature manipulations were independent, effects of mixing depth being more prevalent than effects of temperature. Because mixing depth governs both the light climate and the temperature regime in the mixed surface layer, we propose that climate-driven changes in the timing and depth of water column stratification may have far-reaching consequences for plankton dynamics and should receive increased attention.