Drop In Survival Research Articles

Bacterial Pesticidal Protein Mpp51Aa1 Delivered via Transgenic Citrus Severely Impacts the Fecundity of Asian Citrus Psyllid, Diaphorina citri.

The Asian citrus psyllid (ACP) Diaphorina citri vectors the causative agent of citrus greening disease that has the capacity to decimate citrus production. As an alternative and more sustainable approach to manage D. citri than repeated application of chemical insecticides, we investigated the potential use of the bacteria-derived pesticidal protein, Mpp51Aa1, when delivered by transgenic Citrus sinensis cv. Valencia sweet orange or Citrus paradisi cv. Duncan grapefruit. Following confirmation of transcription and translation of mpp51aa1 by transgenic plants, no impact of Mpp51Aa1 expression was seen on D. citri host plant choice between transgenic and control Duncan grapefruit plants. A slight but significant drop in survival of adult psyllids fed on these transgenic plants was noted relative to those fed on control plants. In line with this result, damage to the gut epithelium consistent with that caused by pore-forming proteins was only observed in a minority of adult D. citri fed on the transgenic Duncan grapefruit. However, greater impacts were observed on nymphs than on adults, with a 40% drop in the survival of nymphs fed on transgenic Duncan grapefruit relative to those fed on control plants. For Valencia sweet orange, a 70% decrease in the number of eggs laid by adult D. citri on transgenic plants was noted relative to those on control plants, with a 90% drop in emergence of progeny. These impacts that contrast with those associated with other bacterial pesticidal proteins and the potential for use of Mpp51Aa1-expressing transgenic plants for suppression of D. citri populations are discussed. IMPORTANCE Pesticidal proteins derived from bacteria such as Bacillus thuringiensis are valuable tools for management of agricultural insect pests and provide a sustainable alternative to the application of chemical insecticides. However, relatively few bacterial pesticidal proteins have been used for suppression of hemipteran or sap-sucking insects such as the Asian citrus psyllid, Diaphorina citri. This insect is particularly important as the vector of the causative agent of citrus greening, or huanglongbing disease, which severely impacts global citrus production. In this study, we investigated the potential of transgenic citrus plants that produce the pesticidal protein Mpp51Aa1. While adult psyllid mortality on transgenic plants was modest, the reduced number of eggs laid by exposed adults and the decreased survival of progeny was such that psyllid populations dropped by more than 90%. These results provide valuable insight for potential deployment of Mpp51Aa1 in combination with other control agents for the management of D. citri.

Out-of-Hospital Cardiac Arrest during the COVID-19 Pandemic: A Systematic Review.

Objective: Out-of-hospital cardiac arrest (OHCA) is a prominent cause of death worldwide. As indicated by the high proportion of COVID-19 suspicion or diagnosis among patients who had OHCA, this issue could have resulted in multiple fatalities from coronavirus disease 2019 (COVID-19) occurring at home and being counted as OHCA. Methods: We used the MeSH term "heart arrest" as well as non-MeSH terms "out-of-hospital cardiac arrest, sudden cardiac death, OHCA, cardiac arrest, coronavirus pandemic, COVID-19, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)." We conducted a literature search using these search keywords in the Science Direct and PubMed databases and Google Scholar until 25 April 2022. Results: A systematic review of observational studies revealed OHCA and mortality rates increased considerably during the COVID-19 pandemic compared to the same period of the previous year. A temporary two-fold rise in OHCA incidence was detected along with a drop in survival. During the pandemic, the community's response to OHCA changed, with fewer bystander cardiopulmonary resuscitations (CPRs), longer emergency medical service (EMS) response times, and worse OHCA survival rates. Conclusions: This study's limitations include a lack of a centralised data-gathering method and OHCA registry system. If the chain of survival is maintained and effective emergency ambulance services with a qualified emergency medical team are given, the outcome for OHCA survivors can be improved even more.

Sars Cov-2/COVID-19 in Multiple Myeloma Latin-American Patients COVID-Lamm Study on Behalf of Gelamm (Grupo de Estudio Latino- Americano de Mieloma Múltiple)

BackgroundThe SARS CoV-2 / COVID 19 pandemic has challenged the world's health systems, especially services that treat cancer. The first studies in China showed that cancer patients had a higher risk of becoming infected and dying. Other risk factors for mortality were age over 65 years, male sex, the presence of comorbidity, hypertension, cardiovascular disease, diabetes, and obesity. Data on the specific behavior of patients with multiple myeloma (MM) in the pandemic are scarce. The mechanisms by which MM patients may have a higher mortality are multiple, derived both from the disease itself due to cellular and humoral immunity deficiency as well as from anti-myeloma treatment. The present study aims to establish the behavior of the disease in the pandemic period in Latin America.MethodsThis is a retrospective case series of in and outpatients with a diagnosis of MM and COVID-19 reported from centers from Latin America between March and July 31, 2020. The analysis of demographic, clinical, laboratory, complications and therapy variables were done using descriptive statistics. A Kaplan Meier survival analysis was performed, with Log Rank statistic. Finally, a Cox regression was performed to identify independent risk factors of worse outcome. Pre-admission characteristics, MM status, and comorbidities constituted the reference model and were used to adjust the association of relevant MM characteristics with mortality. Program used for analysis was SPSS statistics 25.ResultsFifty-two patients with COVID-19 and MM from 7 countries were included. Demographic characteristics, comorbidities, infection baseline clinical conditions, treatment, and outcomes are shown in Table 1. The characteristics in terms of MM status are shown in Table 2.When performing the survival analysis, it is evidenced that the survival of the entire cohort at day 49 was 67% Figure 1. When we focus on patients with comorbidities, survival drops to 53.5% +/- 10.6 (CI 95% 53.4 - 99.4 and p value of 0.041) for the same day Figure 2. When performing the obesity analysis, a drop in survival of up to 39% was observed (95% CI 24.448 - 56.76, with p = 0.00001) Figure 3. Adjusted HR for obesity is 5,078 (95% CI 1,389-18,558, α0.014) and mechanical ventilation with a HR of 3,943 (95% CI - 1,296 - 11,998, α0.016)When comparing patients with controlled MM (> PR) versus uncontrolled, the mortality rate was 84% versus 58% respectively (p = 0.109). Comorbidities (presence of either diabetes, arterial hypertension, cardiovascular disease, or “others”), obesity, need of mechanical ventilation, and <VGPR at the time of infection were independent factors of lower survival Table 3.ConclusionsPatients with MM and COVID-19 has an overall mortality of approximately 30% and this is strongly influenced by the presence of comorbidities, uncontrolled disease and need of mechanical ventilation. Survival of patients without comorbidities and controlled disease is good, suggesting that this group of patients would not require modification of MM therapy. The main limitations of our study are its retrospective nature and the low number of patients. It must be highlighted that at the time of the analysis most of Latin American countries were still in the peak of the pandemic. Prospective studies are required to elucidate the behavior of these risk factors in mortality, to optimize the management of patients with MM in this period of the SARS CoV-2 / COVID-19 pandemic.DisclosuresPeña:BindingSite: Research Funding; Janssen: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity’s Board of Directors or advisory committees; Roche: Membership on an entity’s Board of Directors or advisory committees; Abbvie: Membership on an entity’s Board of Directors or advisory committees; Amgen: Speakers Bureau. Abello:Novartis: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Dr. Reddy’s: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Idrobo:Abbvie: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Rojas:Novartis: Consultancy; Roche: Honoraria; Sandoz: Honoraria; Abbvie: Honoraria. Remaggi:Takeda: Honoraria; Raffo Argentina: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gador Argentina: Research Funding; Amgen: Honoraria, Research Funding. Alvarado:Celgene: Speakers Bureau; Alexion: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau; Roche: Speakers Bureau. De la Peña-Celaya:Amgen: Speakers Bureau; Janssen: Speakers Bureau; Novartis: Speakers Bureau. Perez:Novartis: Speakers Bureau; Celgene: Speakers Bureau; Roche: Speakers Bureau.

Validation of the post-neoadjuvant staging system of the American joint committee on cancer, 8th edition, in patients treated with neoadjuvant chemoradiotherapy followed by curative esophagectomy for localized esophageal squamous cell carcinoma

ObjectiveThe American Joint Committee on Cancer 8th edition staging system presents separate classifications for pTNM and post-neoadjuvant ypTNM (ypTNM-8th) to enhance prognostic prediction after neoadjuvant therapy and surgery. We aimed to validate the ypTNM-8th staging system and to compare the prognostication performance of ypTNM-8th with that of pTNM-7th and pTNM-8th in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (nCRT). MethodsWe reviewed 207 ESCC patients treated with nCRT between January 2007 and December 2014 and compared the Akaike information criterion (AIC) and Harrell's C-index to determine the prognostic performance of each TNM system. ResultsSurvival curve analysis of pTNM-7th and -8th showed a stepwise drop in survival from ypT0N0 to advanced stages, whereas the survival outcome of ypStage III showed a better prognosis than that of ypStage II according to ypTNM-8th. Lymphovascular invasion, perineural invasion, and tumor regression grade were significantly associated with overall survival on univariate analysis. Each TNM system showed significant p-values for trend (p < 0.0001 each), but after adjusting for prognostic factors, ypTNM-8th did not significantly predict survival (p = 0.15), whereas pTNM-7th remained significant (p < 0.001). pTNM-7th incorporating ypT0N0M0 and ypT0 (is)N + M0 as separate groups was superior in prognostication as its AIC was smaller and its C-index was higher than those of pTNM-8th and ypTNM-8th, respectively. ConclusionsBecause ypTNM-8th did not provide sufficient prognostication for patients with ESCC treated with nCRT followed by esophagectomy, more sophisticated prognostic classification should be developed for the ypTNM staging system in these patients.

Improving NICU outcomes–A worldwide endeavor

In this volume of The Journal, D’Apremont et al report on mortality and morbidity outcomes over 15 years (2001-2016) for nearly 14 000 very low birthweight infants (500-1500 grams) at NEOCOSUR centers (30 Neonatal Units from Argentina, Brazil, Chile, Paraguay, Peru, and Uruguay). While many national and international NICU collectives from the US, Canada, Europe, Australia, and Japan have published large scale NICU outcome data, D’Apremont et al provide the first substantial multi-year report from a similar NICU collaborative based in middle-income countries. Despite introducing many evidence-based practices, including increased use of antenatal corticosteroids and noninvasive ventilation, the NEOCOSUR centers did not observe a reduction in mortality in VLBW infants in NICUs. This was probably because of a drop in survival for the most premature babies born at ≤25 weeks gestational age. On the other hand, survival without major morbidity substantially improved for moderately preterm babies >29 weeks gestational age. The NEOCOSUR report demonstrates the ability to collect high quality data from middle-income countries, which is particularly meaningful as neonatal mortality remains stubbornly high in middle- and low-income countries and accounts for over 98% of neonatal mortality worldwide. We hope that NEOCOSUR finds novel ways to compare and contrast their findings with those of high income countries as they continue to improve care for their youngest NICU citizens—these are countries that have learned to walk and deserve to run. Article page 44 ▸ Trends in Perinatal Practices and Neonatal Outcomes of Very Low Birth Weight Infants during a 16-year Period at NEOCOSUR CentersThe Journal of PediatricsVol. 225PreviewTo describe trends in mortality, major morbidity, and perinatal care practices of very low birth weight infants born at NEOCOSUR Neonatal Network centers from January 1, 2001, through December 31, 2016. Full-Text PDF

Disseminated Histoplasmosis in HIV-Infected Patients: A Description of 34 Years of Clinical and Therapeutic Practice.

Disseminated histoplasmosis is the main AIDS-defining infection of French Guiana. We aim to describe our therapeutic experience for 349 patients with disseminated histoplasmosis between 1 January 1981 and 10 January 2014 in French Guiana. Survival, delays for treatment initiation, duration of induction therapy, and associated initial treatments are described. The death rate was 14.9 per 100 person-years, with an early drop in survival. Among those who died, >1/3 died within a year of HIV diagnosis, and ¾ of all patients with histoplasmosis had been diagnosed for HIV within a year. As induction treatment, 29% received liposomal amphotericin B, 12.9% received deoxycholate amphotericin B, 54% received itraconazole alone, and 21.8% received liposomal amphotericin B and itraconazole. The median delay between symptoms-onset and hospitalization was 19.5 days (IQR = 5–105). Liposomal amphotericin B or itraconazole was initiated shortly after admission. Treatment initiation was often presumptive for liposomal amphotericin B (27%) and itraconazole (20%). The median duration of liposomal amphotericin B treatment was 7 days (IQR = 5–11 days). The present study shows that ¾ of the patients were profoundly immunocompromised and had been diagnosed for HIV within the past year. Antifungal treatment was often initiated presumptively on admission. Over time there was a significant gradual decline in early death.

Minimizing Time Fed Rotifers Maximizes Hybrid Striped Bass Larval Growth in Recirculating Aquaculture Systems

AbstractHybrid Striped Bass (HSB; White Bass Morone chrysops × Striped Bass M. saxatilis) represent a valuable sector of the U.S. aquaculture industry. Despite their commercial importance, one factor limiting the growth of the HSB industry is the lack of refined methods to rear larvae in tanks, including the lack of knowledge about optimal rearing conditions, feeding behavior, and efforts to reduce the time larvae spend utilizing live foods. Four‐day‐old HSB larvae were stocked into two recirculating aquaculture systems (72.0–73.9 larvae/L) maintained at 18°C and 26°C. Larvae were fed three times daily with either rotifers Brachionus plicatilis (60 rotifers · mL−1 · tank−1 · d−1) or brine shrimp Artemia sp. (12 Artemia · mL−1 · tank−1 · d−1) according to the designated replicated treatment for 2–12 d in 2‐d increments where larvae were progressively weaned from rotifers onto Artemia. The number of days fed rotifers (DFR) had no significant effect on survival of larvae reared at either 18°C (46.6%) or 26°C (30.2%). However, there was a significant difference in larval survival between the two temperatures. Larvae were measured at the conclusion of the study, and those reared at 18°C were shorter (8.00 mm TL) than those reared at 26°C (9.59 mm TL); TL and body depth of larvae varied significantly among treatments by temperature, DFR, and their interaction. These results demonstrate that minimizing the time spent feeding on rotifers maximized the growth of HSB larvae. Results also indicate that Artemia is a suitable diet for 6‐d‐old larval HSB and that the fish can easily be weaned from rotifers at both optimum (26°C) and suboptimum (18°C) culture temperatures while maintaining suitable growth. Notably, this was achieved with no significant drop in survival. Additional research is needed to optimize Artemia nauplius feeding regimes to minimize the time for which HSB must be given live feeds in order to wean to a dry diet more quickly while optimizing growth and survival.

Staging and Survival of Colorectal Cancer (CRC) in Octogenarians: Nationwide Study of U.S. Veterans: 2017 Presidential Poster Award

Introduction: USPSTF recommends against continuing screening for colorectal cancer past 75 years in adequately screened individuals. Research has shown that one time screening for elderly who have never been screened appears to be cost effective until 86 years of age. Risk stratification should be made based on life expectancy and risk to benefit ratio. Survival and staging data that compares elderly vs younger populations has not been published. Objective:1)To compare staging(0-4) of CRC in groups of 60-69, 70-79 and 80-89 year olds. 2)To compare survival outcomes(5-10 years) in stages 0-2 for these age groups after treatment i.e. surgery. 3)To compare surgical and no treatment (i.e. no surgery) survival outcomes in these age groups.Figure: Image 1.Figure: Image 2.Figure: Image 3.Methods: In a retrospective study, male veterans were selected from Veterans Affairs National Cancer Cube Registry. 22,735 patients within 60-69, 18,390 within 70-79 and 10,057 within 80-89 years were diagnosed with CRC from year 2000-2015 with majority being stage 1& 2[Image1]. Surgical and survival data were obtained only for stage 0-2 as surgery is the current standard of treatment for these stages. Results: After surgery, 5-10 year survival for 60-69 age group averaged about 34.4%[95%CI 31.94, 36.85] for stage 0-2. Similarly, for 70-79 and 80-89 age group it was 30.86%[95%CI 29.54, 32.19] and 25.45%[95% CI 24.77, 25.69] respectively[Image2]. The 5-10 year survival data for patients without treatment i.e. not undergoing surgery was 1.03%[95%CI 0.32, 1.74], 0.81%[95% CI -0.10, 1.73], and 0.95%[95%CI 0.33, 1.56] for age groups 60-69, 70-79 and 80-89 respectively[Image3]. When compared to surgery vs. no treatment there was significant difference( P<0.05) in all age groups for survival 5-10 years. Conclusion: Highest number of CRC cases diagnosed across each age group were stage 1 with stage 2 being second. In the surgical treatment group survival was statistically different for 80-89 age group as compared to 60-69 and 70-79, though octogenarians did have a surprisingly high mean of 25.45% suggesting early detection and treatment will help survival. Survival data from surgery and no-treatment cases showed an immense drop in survival for non-treated patients suggesting these candidates may have other reasons or comorbid conditions leading to their demise. Overall data showing early stage at cancer diagnosis and comparable surgical survival in octogenarians suggest those who have life expectancy 5-10 years could benefit from continued screening and treatment.

Natural history and risk stratification of patients undergoing non-invasive ventilation in a non-ICU setting for severe COPD exacerbations.

Non-invasive ventilation (NIV) delivered in an intensive care unit (ICU) has become the cornerstone in the treatment of patients with severe chronic obstructive pulmonary disease (COPD) exacerbations. A trend towards managing these patients in non-ICU setting has emerged in recent years, although out-of-hospital survival by this approach and how to prognosticate it is unknown. We aimed to investigate these issues. We consecutively recruited 100 patients (49 males; median age 82years) who received NIV treatment for acute respiratory failure due to COPD exacerbation in non-ICU medical wards of our hospital, between November 2008 and July 2012. We assessed survival (both in-hospital and out-of-hospital) of all these patients, and analyzed baseline parameters in a Cox proportional hazards model to develop a prognostic score. The median survival in the study population was 383days (240-980). Overall survival rates were 71.0, 65.3, and 52.7% at 1, 3, and 12months, respectively. Age>85years, a history of heart disorders and a neutrophil count≥10×10(9) were associated with higher mortality at Cox's analysis (χ (2)=35.766, p=0.0001), and were used to build a prognostic score (NC85). The presence of two or more factors determined the deepest drop in survival (when NC85≥2, mortality at 1, 3, and 12 was 60.7, 70.4, and 77.2%, respectively, while when NC85=0 were 4.0, 4.0, and 14.0%). A simple model, based on three variables (age, neutrophil count and history of heart disease), accurately predicts survival of COPD patients receiving NIV in a non-ICU setting.

Peritoneal dissemination from high-grade appendiceal cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown variability in survival outcomes when used to treat peritoneal surface disease (PSD) from appendiceal and colorectal cancers. The primary goal of this study was to examine outcomes for high-grade appendiceal (HGA) and high-grade colonic primaries after CRS-HIPEC to determine if a significant difference exists between the two groups. A retrospective analysis of patients with peritoneal dissemination from appendiceal and colonic primaries were identified in a prospectively maintained database of 1,223 CRS-HIPEC procedures performed between 1991 and 2015. Patient demographics, performance status resection status, tumor grade, nodal status, morbidity, mortality, and survival were reviewed with biopsy-proven PSD being classified according to primary site. Univariate and multivariate analyses were performed, and outcomes compared. The study identified 171 CRS-HIPEC procedures for 165 patients: 110 (66.7%) for HGA and 55 (33.3%) for high-grade colonic lesions. Observed median disease-free survival (DFS) and overall survival (OS) for both groups were the same at14.4 and 18 months, respectively. Median survival according to resection status for R0/R1, R2a, and R2b/c were 36, 15.6, and 8.4 months (P<0.0001). Median OS for those who received preoperative chemotherapy versus those who did not were 14.4 and 20.4 months, respectively (P=0.01). For those who received preoperative chemotherapy, no difference was apparent in the DFS interval (P=0.34). Multivariate predictors of OS included resection status (P<0.0001) and lymph node involvement (P=0.0005). Preoperative chemotherapy offered no clear DFS or OS benefit, for HGA or high-grade colon cancer patients. Complete cytoreduction offered the greatest survival benefit to both groups with a correlating drop in survival to resection status. Outcomes for high grade appendiceal cancer are remarkably similar to colon cancer.

Development of larval culture methods for blue-legged gold coral banded shrimp Stenopus cyanoscelis: effects of prey type and prey density

The blue-legged gold coral banded shrimp, Stenopus cyanoscelis, is among the most popular marine ornamental shrimp; however, no information on its larval culture is available. A 40-day experiment was performed to evaluate effects of prey type and prey density on survival and development of early S. cyanoscelis larvae. Newly hatched larvae were fed rotifers at densities of 5, 25 or 50/ml or Artemia nauplii at densities of 2, 5 or 10/ml. In all treatments, larval survival up to 6 days after hatch (DAH) was high (≥80 %). However, larvae fed rotifers at 5/ml suffered a steep drop in survival after 6 DAH, and total mortality occurred by 14 DAH, when survival in all other treatments ranged from 30 to 50 %. Between 15 and 30 DAH, S. cyanoscelis larvae fed 25 or 50 rotifers/ml showed consistently higher survival than Artemia-fed larvae. However, this situation reversed after 25 DAH, when survival of rotifer-fed larvae decreased sharply while the initial high mortalities of Artemia-fed S. cyanoscelis larvae stabilized around 17 DAH and those fed 5 Artemia/ml showed the highest survival. Meanwhile, linear regression of larval molting rates and DAH showed a negative relationship for rotifer-fed larvae and a positive relationship for Artemia-fed larvae with time. In summary, our findings suggest that an appropriate feeding regime for S. cyanoscelis larvae is provision of rotifers at 50/ml for the first 20−25 DAH, then introducing Artemia nauplii at 5/ml from 17 DAH. This study is a first important step towards developing appropriate larval culture techniques for S. cyanoscelis.

Laboratory investigation of high pressure survival in Shewanella oneidensis MR-1 into the gigapascal pressure range.

The survival of Shewanella oneidensis MR-1 at up to 1500 MPa was investigated by laboratory studies involving exposure to high pressure followed by evaluation of survivors as the number (N) of colony forming units (CFU) that could be cultured following recovery to ambient conditions. Exposing the wild type (WT) bacteria to 250 MPa resulted in only a minor (0.7 log N units) drop in survival compared with the initial concentration of 108 cells/ml. Raising the pressure to above 500 MPa caused a large reduction in the number of viable cells observed following recovery to ambient pressure. Additional pressure increase caused a further decrease in survivability, with approximately 102 CFU/ml recorded following exposure to 1000 MPa (1 GPa) and 1.5 GPa. Pressurizing samples from colonies resuscitated from survivors that had been previously exposed to high pressure resulted in substantially greater survivor counts. Experiments were carried out to examine potential interactions between pressure and temperature variables in determining bacterial survival. One generation of survivors previously exposed to 1 GPa was compared with WT samples to investigate survival between 37 and 8°C. The results did not reveal any coupling between acquired high pressure resistance and temperature effects on growth.

Annexin-A2 as predictor biomarker of recurrent disease in endometrial cancer.

Endometrial carcinomas, the most common malignant tumour of the female genital tract, are usually diagnosed at an early stage with uterine-confined disease and an overall favourable prognosis. However, up to 20% of endometrial carcinomas will end up in recurrent disease, associated with a drop in survival and representing the major clinical challenge. Management of this group of risk patients relies on robust biomarkers that may predict which endometrial carcinomas will relapse. For this, we performed a proteomic analysis comparing primary lesions with recurrences and identified ANXA2 as a potential biomarker associated with recurrent disease that we further validated in an independent series of samples by immunohistochemistry. We demonstrated in vitro a role for ANXA2 in the promotion of metastasis rather than interfering with sensitivity to radio/chemotherapy. In addition, ANXA2 silencing resulted in a reduced metastatic pattern in a mice model of endometrial cancer dissemination, with a limited presence of circulating tumor cells. Finally, a retrospective study in a cohort of 93 patients showed that ANXA2 effectively predicted those endometrioid endometrial carcinomas that finally recurred. Importantly, ANXA2 demonstrated a predictive value also among low risk Stage I endometrioid endometrial carcinomas, highlighting the clinical utility of ANXA2 biomarker as predictor of recurrent disease in endometrial cancer. Retrospective and prospective studies are ongoing to validate ANXA2 as a potential tool for optimal stratification of patients susceptible to receive radical surgery and radio/chemotherapy.

Double Refractory Myeloma: Analysis Of Clinical Outcomes and Medical-Resource Utilisation In a Single Centre

BackgroundIntroduction of proteasome inhibitors and immunomodulatory agents over the last decade has improved survival for multiple myeloma (MM) patients. A retrospective analysis of patients who developed resistance/intolerance to these agents showed a median overall survival (OS) and progression-free survival (PFS) of 9 months and 5 months, respectively (Kumar et al. 2012). Recent clinical trials have focused on improving outcomes for these double-refractory (DR) patients. However very limited published data from real world clinical practice is available on clinical outcomes and medical-resource utilisation (MRU) costs for this cohort of patients. We have analysed clinical outcomes and patient-level MRU costs of double-refractory/intolerant patients in a single centre. MethodsData on clinical outcomes, anti-myeloma therapies prescribed and MRU were obtained from a single centre in Oxford, UK, for 36 MM patients who have received four lines of treatment between 2011 and 2013. Six patients had not received prior bortezomib due to neuropathy. For ease of comparison and uniformity, thirty patients pre-treated with lenalidomide and bortezomib who had progressed on last therapy were included in this analysis (83% of the cohort). Clinic attendances, inpatient admissions, supportive therapies, transfusions and blood tests from start of fourth-line therapy until death or last follow-up were retrieved from health care records. Survival analysis was performed; Kaplan–Meier survival plots were generated to evaluate OS and PFS following initiation of fourth-line therapy. The occurrences of MRU were extracted to estimate the use and cost of each, using the UK NHS schedule of reference costs 2011-12 and published sources. ResultsPatients were selected for analysis on the basis of having received/receiving four lines of anti-MM therapy. Patient characteristics are summarised in Figure 1. Median age at diagnosis was 65.3 years (48–83 years). When offered a choice of therapy 77% of patients preferred an active treatment to care with palliative intent. The mean age of those who chose palliative care was 75.8 years compared to 63.7 for active therapy (p = 0.003). Treatment regimens were typically bendamustine based (53%), retreatment with bortezomib (10%) or lenalidomide based (27%). Patients were treated for a mean of 15.3 weeks (SD: 11.3).There were 42 hospital admissions reported during fourth-line, lasting 8 days on average. Patients required 6.8 red blood cell units and 2.9 platelet units on average. At least one RBC and platelet transfusion was required by 22 and 13 patients respectively. Median PFS in this cohort was 11 weeks and median OS was 23 weeks; however, the sample size was too small to obtain definitive PFS or OS conclusions. There was steep drop in survival early on (Figure 2), with a small number of patients surviving over a longer period. The most common Grade 3-4 adverse events were anaemia (60%), thrombocytopaenia (57%) and bone pain (37%). Eighteen out of the 30 patients had died by the end of follow-up, of whom 78% died in hospital. Prolonged inpatient stays, frequent adverse events and high transfusion requirements suggest poor quality of life (QoL) among these patients.Outpatient and day therapy unit attendances occurred frequently, with 4.3 and 12.6 per patient respectively over the mean treatment duration of 15.3 weeks. Investigations including CT and MRI scans were performed in 33% of patients. Blood tests were frequent, with mean full blood count testing of 21.6 per patient.The mean drug cost of fourth-line anti-MM therapy was £5,101 per patient. The mean MRU cost during fourth-line therapy was £11,160: clinical attendances £5,015 (45%); inpatient admissions £2,999 (27%); transfusions £2,479 (22%); supportive therapy £498 (4%); blood tests £169 (2%). The mean total cost of treatment plus MRU was therefore £16,260 [£9,201–23,320]; £1,066 per week on treatment. ConclusionOver 75% of myeloma patients in the fourth-line setting want to be treated with an active intent to improve survival. PFS and OS in our cohort were similar to published estimates. These patients, due to the nature of their disease, have high MRU costs. Therapies that induce higher response rates or reduce disease progression could lower MRU costs and improve QoL. Our data will provide an optimal comparison when formal cost-effectiveness evaluation is performed with new therapies for this DR cohort. [Display omitted] [Display omitted] Disclosures:Gooding:Celgene: Unrestricted Educational Grant Other. Lau:Celgene: Unrestricted Educational Grant Other. Sheikh:Celgene: Unrestricted Educational Grant Other. Roberts:Celgene: Unrestricted Educational Grant Other. Wong:Celgene: Unrestricted Educational Grant Other. Dickens:Celgene: Unrestricted Educational Grant Other. Elvidge:Celgene: Consultancy. Lee:Celgene: Consultancy. Ramasamy:Celgene: Honoraria, Unrestricted Educational Grant Other.

Giant adrenocortical carcinoma with 27-month disease-free survival by surgical resection alone: A case report

Adrenocortical cancer (ACC) is a rare disease with an estimated incidence of 1-2/million/year. The tumour stage and completeness of surgical resection have the biggest impact on survival. Whereas stage I-II patients survive in 55-64% of cases, only 0-5% of patients with stage IV disease are still alive at 5 years. A median survival of 33 months can be expected after curative surgery. Incomplete surgery leads to a significant drop in survival. We present a 40-year-old man who underwent a technically demanding complete surgical excision of a giant (26 cm, 2372 g) ACC and experienced a 27-month disease-free survival without any systemic treatment. Detailed description of the surgical anatomy in relation to tumour size and patient body constitution is provided. The surgical strategy and exposure pitfalls under such extreme circumstances are discussed. To achieve R0 resection in locally advanced disease, en bloc resection with neighbouring organs is widely recommended. Giant tumours may however pose a technical challenge due to space constraints.

Effect ofCotesia rubecula(Hymenoptera: Braconidae) on Survival of Larval Cohorts ofPieris rapae(Lepidoptera: Pieridae) on Collards: Evaluation of an Introduced Biological Control Agent

Survival of artificial cohorts of larvae of the imported cabbageworm, Pieris rapae (L.), was assessed in a collard (Brassica oleracea L., var. acephala) patch on an organic vegetable farm in western Massachusetts. We recorded a significant drop in survival of larvae between the 4th and 5th instar due to parasitism by the parasitoid Cotesia rubecula (Marshall), which was introduced to New England from China in 1988. This was a large change from the survivorship pattern of P. rapae observed in the same area in 1985–1986, in which there was a significant drop in survival between 5th instars and pupae due to Cotesia glomerata (L.), the dominant parasitoid of P. rapae in New England at the time. In our study, parasitism by C. rubecula averaged 62.4 ± 8.6%, while no parasitism by C. glomerata was observed. The introduction of C. rubecula is now very likely to be benefitting organic vegetable producers in western Massachusetts, killing more larvae and at an earlier life stage than the previous parasitoid, reducing the potential for damage to cole crops.

2. Roles of intracellular ice formation, vitrification of cell water, and recrystallization of intracellular ice on the survival of mouse embryos and oocytes

Although sperm were successfully cryopreserved in 1950, another 22 years elapsed before the successful preservation of a mammalian embryo. In 1963, I had carried out physical–chemical analyses indicating that if cells were cooled too rapidly, they would undergo lethal intracellular ice formation (IIF), and defined what is meant by “too rapidly” for a particular cell. To avoid IIF, the cell had to dehydrate during cooling, and the required rate of cooling depended chiefly on the permeability of a particular cell to water and on the temperature coefficient of that permeability. Between 1968 and 1972, Stanley Leibo and I turned our attention to the survival of yeast, mouse marrow stem cells, and Chinese Hamster tissue culture cells as functions of cooling rate and temperature. We found that plots of survival vs. cooling rate formed an inverted “U”, with high survivals at a medium rate, and lower survivals after very slow and very rapid cooling. We proposed a “Two-Factor” hypothesis which stated that the right hand arm of the inverted U was a result of IIF at high cooling rates. Interestingly, the optimum cooling rate for maximum survival varied over a wide range for the different cells. This was chiefly because the cells differed widely in water permeability and the temperature coefficient of that permeability. In fact if the known values of these parameters were used to generate the theoretical curves, the predicted relation between IIF and cooling rate agreed quite closely with the observed drop in survival vs. cooling rate. In 1971 David Whittingham reported the successful cryopreservation of mouse 8-cell embryos cooled at 50 °C/min in PVP. Leibo and I were excited but perplexed about these results – perplexed because our computations indicated that mouse embryos would undergo lethal IIF when cooled at that rate. We calculated that the cooling rate would have to be about 1 °C/min.. That turned out to be the case. With that change and the substitution of Me 2 SO for PVP, David, Stanley and I obtained very good in vitro and in vivo survival of 8-cell embryos cooled to −196 °C (or −269 °C). The ability to cryopreserve mouse embryos quickly had important applied consequences and important fundamental consequences. Perhaps, the most important direct application was that it permitted the long-term maintenance of thousands of mutant lines of mice in the form of preimplantation embryos in a few liquid nitrogen tanks. The indirect applications stemmed from the fact that essentially the same procedures worked for early embryos of over 20 other mammals, including humans. In the last decade, clinical interest has been emphasizing the cryopreservation of human oocytes. They have proved more difficult to freeze and so interest has shifted somewhat to cryopreserving them by vitrification. As discussed, one way to avoid lethal IIF is to cool cells slowly enough so that the freezable water in the cell flows out of the cell and freezes externally. An alternative approach is to avoid intracellular ice by vitrifying cellular water. Vitrification involves converting water into a non-crystalline or amorphous glass. To achieve this conversion, it has been the strong belief that cells have to be in solutions containing a very high concentration of glass-inducing solutes and have to be cooled very rapidly. In recent work, however, we have found that neither of these is true for mouse oocytes. The important factor is not the cooling rate – it is the warming rate, and the warming rate has to be very high. Furthermore, if the warming rate is very high, one can cut in half the concentration of solutes in the vitrification solution and still obtain high survivals.

High temperature and dehydration tolerance of the red velvet mite, Balaustium sp. (Erythraeidae), permit the exploitation of extremely hot, dry microhabitats

Red velvet mites Balaustium sp. nr. putmani, a mite commonly associated with landscaping projects throughout the Midwestern United States, show a particular affinity for warm, sunny locations. Adults display a remarkable tolerance for high temperature, capable of actively crawling on extremely hot surfaces for extended periods. To determine the upper thermal tolerance of this mite, we compared short-term 1-hour heat-shock responses, coupled with a behavioural scoring system, among all mobile instars (larva, deutonymph and adult) that occur on hot surfaces. Maximum heat shock for 50% survival was 48°C for larvae, 52°C for deutonymphs and 52–54°C for adults, which is high for an acarine and indicates that the active instars of this mite are generally resistant to heat stress. Larvae experienced their first major drop in survival of ≥20% between 42°C and 44°C; this drop occurred at 48–50°C for deutonymphs and 50–52°C for adults. A distinguishing feature of deutonymphs and adults is their ability to recover from heat-induced injury, something that larvae apparently lack. This recovery is characterized by an abrupt injury/mortality at 52°C (nearly all survive heat shocks of 40–48°C) for adults and deutonymphs, whereas the response in larvae is graded following a dose–response from 42°C to 50°C. Our conclusion is that enhanced high-temperature tolerance coincides with heat-shock recovery in deutonymphs and adults that are active for longer periods of time during the hottest periods each year. The larval season occurs early during the cooler spring, which facilitates the establishment of populations. Balaustium sp. nr. putmani requires a dry habitat to function properly. It seems reasonable to suggest that sunny sites create ideal dry habitats for B. sp. nr. putmani to thrive, and increased sun exposure at these preferred dry sites simultaneously requires that these mites are heat tolerant.

Accumulation and Effects of Natural Mixtures of Persistent Organic Pollutants (POP) in Zebrafish after Two Generations of Exposure

Effects of exposure to environmentally realistic mixtures of persistent organic pollutants (POP) harvested from aquatic ecosystems in Norway were studied in an in vivo zebrafish model. POP were extracted from burbot (Lota lota) liver from two separate lakes, Lake Losna and Lake Mjøsa, and exposed to zebrafish through the diet in a two-generation study. Effects on survival, growth, sex ratio, and timing of puberty were investigated. In addition, the biomarkers 7-ethoxyresorufin O-deethylase (EROD) and vitellogenin (Vtg) were measured. The ratios of contaminant levels in extracts collected from Lake Mjøsa:Lake Losna were 6, 10, and 270 for polychlorinated biphenyls (PCB), dichlorodiphenyltrichloroethanes (DDT), and polybrominated diphenyl ethers (PBDE), respectively. The concentration range of POP measured in zebrafish was lower than in burbot originating from Lake Mjøsa, but comparable to concentrations previously reported in humans and wildlife. The results showed that exposure to environmentally realistic mixtures of POP exerted a negative effect on survival of fish in both generations. The marked drop in survival during 9–20 days post fertilization (dpf) suggested that this period may be a critical window for development. In both generations an earlier onset of puberty was observed and a higher proportion of males than females was noted in exposed fish compared to controls. Suprising effects of exposure were found on body weight. In the first generation (F0), body weight was significantly higher in both exposure groups compared to controls, while in the next generation (F1) the same exposures were associated with a decrease in body weight. Zebrafish exposed to relatively low quantities of POP showed a significant induction of biomarkers (EROD and Vtg), while fish exposed to higher exposure doses did not demonstrate induction.

Steep past and future population decline in an arctic wader: dynamics and viability of Baltic Temminck's stints Calidris temminckii

Decline of migrant wader populations worldwide implies that their demography may be affected by phenomena occurring in a large geographical scale. Knowledge about vital rates affecting population growth and viability helps in finding the processes behind the declines. We estimated the rate of population growth (λ) of a dramatically declined population of Temminck's stints Calidris temminckii using a ten year capture–recapture data. We assessed the viability of the population by projections based on λ and its variation. We also studied sensitivity of λ to changes in vital rates (breeding success, recruitment and adult survival). Both adult and juvenile survival and breeding success were lower than c. 30 years earlier. Adult survival seemed to have dropped during the study period. Population growth appeared strongly negative and viability analyses predicted an almost certain extinction within a few decades. Adult survival formed the main component of the growth rate suggesting that population crash is mainly caused by a drop in adult survival. Still, sensitivity analyses showed that a moderate rise in adult survival or any other single vital rate would not make the population viable. Most probably, survival has dropped due to factors operating along migration routes and wintering areas, at sites shared by birds from other parts of the breeding range. Therefore, the observed population crash and decline in adult survival may indicate parallel changes in poorly monitored arctic populations. Migration habits (continental wide flyways and scattered wintering areas) imply that factors responsible for the drop in survival have a wide geographical range.