bluuebunny/crossref_metadata_2025 huggingface dataset:
Pro-fibrinolytic potential of the third larval stage of Ascaris suum as a possible mechanism facilitating its migration through the host tissues
Authors: Diosdado Alicia , Simón Fernando , Morchón Rodrigo , González-Miguel Javier
Published: April 2020

Background

Ascaris roundworms are the parasitic nematodes responsible for causing human and porcine ascariasis. Whereas A. lumbricoides is the most common soil-transmitted helminth infecting humans in the world, A. suum causes important economic losses in the porcine industry. The latter has been proposed as a model for the study of A. lumbricoides since both species are closely related. The third larval stage of these parasites carries out an intriguing and complex hepatopulmonary route through the bloodstream of its hosts. This allows the interaction between larvae and the physiological mechanisms of the hosts circulatory system, such as the fibrinolytic system. Parasite migration has been widely linked to the activation of this system by pathogens that are able to bind plasminogen and enhance plasmin generation. Therefore, the aim of this study was to examine the interaction between the infective third larval stage of A. suum and the host fibrinolytic system as a model of the host-Ascaris spp. relationships.

Methods

Infective larvae were obtained after incubating and hatching fertile eggs of A. suum in order to extract their cuticle and excretory/secretory antigens. The ability of both extracts to bind and activate plasminogen, as well as promote plasmin generation were assayed by ELISA and western blot. The location of plasminogen binding on the larval surface was revealed by immunofluorescence. The plasminogen-binding proteins from both antigenic extracts were revealed by two-dimensional electrophoresis and plasminogen-ligand blotting, and identified by mass spectrometry.

Results

Cuticle and excretory/secretory antigens from infective larvae of A. suum were able to bind plasminogen and promote plasmin generation in the presence of plasminogen activators. Plasminogen binding was located on the larval surface. Twelve plasminogen-binding proteins were identified in both antigenic extracts.

Conclusions

To the best of our knowledge, the present results showed for the first time, the pro-fibrinolytic potential of infective larvae of Ascaris spp., which suggests a novel parasite survival mechanism by facilitating the migration through host tissues.
Exploring the relationship between susceptibility to canine leishmaniosis and anti-Phlebotomus perniciosus saliva antibodies in Ibizan hounds and dogs of other breeds in Mallorca, Spain
Authors: Burnham Alexis C. , Ordeix Laura , Alcover M. Magdalena , Martínez-Orellana Pamela , Montserrat-Sangrà Sara , Willen Laura , Spitzova Tatiana , Volf Petr , Solano-Gallego Laia
Published: April 2020

Background

Canine leishmaniosis caused byLeishmania infantumis a neglected zoonosis transmitted by sand flies likePhlebotomus perniciosus. Clinical signs and disease susceptibility vary according to various factors, including host immune response and breed. In particular, Ibizan hounds appear more resistant. This immunocompetence could be attributed to a more frequent exposure to uninfected sand flies, eliciting a stronger anti-sand fly saliva antibody response.

Methods

This study aimed to investigate the prevalence of anti-P. perniciosussaliva antibodies in Ibizan hounds and dogs of other breeds in theLeishmania-endemic area of Mallorca, Spain, and to correlate these antibody levels with clinical, immunological and parasitological parameters. Anti-sand fly saliva IgG was examined in 47 Ibizan hounds and 45 dogs of other breeds using three methods:P. perniciosuswhole salivary gland homogenate (SGH) ELISA; recombinant protein rSP03B ELISA; and rSP03B rapid tests (RT). Additionally, diagnostic performance was evaluated between methods.

Results

Results indicate significantly higher anti-SGH antibodies (P = 0.0061) and a trend for more positive SGH ELISA and RT results in Ibizan hounds compared to other breeds. General linear model analysis also found breed to be a significant factor in SGH ELISA units and a marginally significant factor in RT result. Although infection rates were similar between groups, Ibizan hounds included significantly more IFN-γ producers (P = 0.0122) and papular dermatitis cases (P< 0.0001). Older age andL. infantumseropositivity were also considered significant factors in sand fly saliva antibody levels according to at least one test. Fair agreement was found between all three tests, with the highest value between SGH and rSP03B RT.

Conclusions

To our knowledge, this is the first study elaborating the relationship between anti-P. perniciosussaliva antibodies and extensive clinical data in dogs in an endemic area. Our results suggest that Ibizan hounds experience a higher frequency of exposure to sand flies and have a stronger cellular immune response toL. infantuminfection than other breed dogs. Additional sampling is needed to confirm results, but anti-P. perniciosussaliva antibodies appear to negatively correlate with susceptibility toL. infantuminfection and could possibly contribute to the resistance observed in Ibizan hounds.
Fast multiplex real-time PCR assay for simultaneous detection of dog and human blood and Leishmania parasites in sand flies
Authors: Sales Kamila Gaudêncio da Silva , Miranda Débora Elienai de Oliveira , Paiva Marcelo Henrique Santos , Figueredo Luciana Aguiar , Otranto Domenico , Dantas-Torres Filipe
Published: April 2020

Background

The blood-feeding behaviour of female sand flies may increase their likelihood of acquiring and transmitting Leishmania parasites. Studies on the host usage by these insects may thus improve our understanding of the Leishmania transmission risk in leishmaniasis-endemic areas. Here, we developed a fast multiplex real-time PCR assay for simultaneous detection of dog, human and Leishmania DNA in sand flies.

Methods

Primers and TaqMan probes targeting the mitochondrial cytochrome c oxidase subunit 1 and cytochrome b genes of dog and human, respectively, were combined in a multiplex assay, which also includes primers and a TaqMan probe targeting the Leishmania minicircle kinetoplast DNA.

Results

The multiplex assay was 100% specific, with analytical sensitivities of 103 fg/reaction for dog and human and 1 fg for Leishmania. By testing field-collected engorged female sand flies (95 Migonemyia migonei and two Nyssomyia intermedia), 50 M. migonei were positive for one or two targets (positivity rates: 45.4% for human, 4.1% for dog and 12.4% for Leishmania DNA).

Conclusions

This multiplex real-time PCR assay represents a novel fast assay for detecting dog, human and Leishmania DNA in female sand flies and therefore a tool for assessing the risk of Leishmania transmission to these hosts in areas of active transmission.
Data quality predicts care quality: findings from a national clinical audit
Authors: Yates Mark , Bechman Katie , Dennison Elaine M. , MacGregor Alexander J. , Ledingham Jo , Norton Sam , Galloway James B.
Published: April 2020

Background

Missing clinical outcome data are a common occurrence in longitudinal studies. Data quality in clinical audit is a particular cause for concern. The relationship between departmental levels of missing clinical outcome data and care quality is not known. We hypothesise that completeness of key outcome data in a national audit predicts departmental performance.

Methods

The National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis (NCAREIA) collected data on care of patients with suspected rheumatoid arthritis (RA) from early 2014 to late 2015. This observational cohort study collected data on patient demographics, departmental variables, service quality measures including time to treatment, and the key RA clinical outcome measure, disease activity at baseline, and 3 months follow-up. A mixed effects model was conducted to identify departments with high/low proportions of missing baseline disease activity data with the results plotted on a caterpillar graph. A mixed effects model was conducted to assess if missing baseline disease activity predicted prompt treatment.

Results

Six thousand two hundred five patients with complete treatment time data and a diagnosis of RA were recruited from 136 departments. 34.3% had missing disease activity at baseline. Mixed effects modelling identified 13 departments with high levels of missing disease activity, with a cluster observed in the Northwest of England. Missing baseline disease activity was associated with not commencing treatment promptly in an adjusted mix effects model, odds ratio 0.50 (95% CI 0.41 to 0.61, p < 0.0001).

Conclusions

We have shown that poor engagement in a national audit program correlates with the quality of care provided. Our findings support the use of data completeness as an additional service quality indicator.
Correction to: Investigating psychometric properties of the Thai version of the Zarit Burden Interview using rasch model and confirmatory factor analysis
Authors: Pinyopornpanish Kanokporn , Pinyopornpanish Manee , Wongpakaran Nahathai , Wongpakaran Tinakon , Soontornpun Atiwat , Kuntawong Pimolpun
Published: April 2020

Following the publication of the original article [1], the authors unfortunately became aware of the following errors in Table 3:
AutoGrow4: an open-source genetic algorithm for de novo drug design and lead optimization
Authors: Spiegel Jacob O. , Durrant Jacob D.
Published: April 2020

We here present AutoGrow4, an open-source program for semi-automated computer-aided drug discovery. AutoGrow4 uses a genetic algorithm to evolve predicted ligands on demand and so is not limited to a virtual library of pre-enumerated compounds. It is a useful tool for generating entirely novel drug-like molecules and for optimizing preexisting ligands. By leveraging recent computational and cheminformatics advancements, AutoGrow4 is faster, more stable, and more modular than previous versions. It implements new docking-program compatibility, chemical filters, multithreading options, and selection methods to support a wide range of user needs. To illustrate both de novo design and lead optimization, we here apply AutoGrow4 to the catalytic domain of poly(ADP-ribose) polymerase 1 (PARP-1), a well characterized DNA-damage-recognition protein. AutoGrow4 produces drug-like compounds with better predicted binding affinities than FDA-approved PARP-1 inhibitors (positive controls). The predicted binding modes of the AutoGrow4 compounds mimic those of the known inhibitors, even when AutoGrow4 is seeded with random small molecules. AutoGrow4 is available under the terms of the Apache License, Version 2.0. A copy can be downloaded free of charge from http://durrantlab.com/autogrow4.
Influenza NG-34 T cell conserved epitope adjuvanted with CAF01 as a possible influenza vaccine candidate
Authors: Sisteré-Oró Marta , Pedersen Gabriel K. , Córdoba Lorena , López-Serrano Sergi , Christensen Dennis , Darji Ayub
Published: April 2020

Conserved epitopes are targets commonly researched to be part of universal vaccine candidates against influenza viruses (IV). These conserved epitopes need to be cross-protecting against distinct IV subtypes and to have a strong immunogenic potential. Nevertheless, subunit vaccines generally require a strong adjuvant to enhance their immunological effects. Herewith, we compare four different adjuvants differing in their immunological signatures that may enhance efficacy of a conserved hemagglutinin (HA)-epitope from IV, the NG-34, to define the most efficient combination of antigen/adjuvant to combat IV infections. Soluble NG-34 was mixed with adjuvants like aluminium hydroxide (AH) and AddaVax, known to induce Th2 and humoral responses; CAF01 which displays a biased Th1/Th17 profile and Diluvac Forte which augments the humoral response. Combinations were tested in different groups of mice which were subjected to immunological analyses. CAF01 + NG-34 induced a complete immune response with the highest IgG1, IgG2c titers and percentages of activated CD4 T cell promoting IFN-γ, IL-2 and TNF-α producing cells. Furthermore, in NG-34 stimulated mice splenocytes, cytokine levels of IFN-γ, IL-1β, IL-6, IL-10, IL-17 and TNF-α were also the highest in the CAF01 + NG-34 mouse group. This complete induced immune response covering the humoral and the cellular arms of the adaptive immunity promoted by CAF01 + NG-34 group suggests that CAF01 could be a good candidate as an adjuvant to combine with NG-34 for an efficacious vaccine against IV. However, more studies performed in IV hosts as well as studies with a challenge model are further required.
Semi-analytical solutions for the diffusive logistic equation with mixed instantaneous and delayed density dependence
Authors: Alfifi H. Y.
Published: April 2020

In this work, the semi-analytical solution is studied for the diffusive logistic equation with both mixed instantaneous and delayed density. The domain of reaction–diffusion in one dimension is shown. Delay partial differential equation is approximated with a delay ordinary differential equation system by using the Galerkin technique method. Steady-state solutions and stability analysis as well as bifurcation diagrams are derived. The effect of diffusion parameter and delay values is comprehensively studied; as a result, both parameters can destabilize or stabilize the model. We obtained that the decrease in values of the Hopf bifurcations for growth rate is associated with an increase in delay values, whereas the diffusion parameter is increased. Furthermore, comparisons between the numerical simulations and semi-analytical results present a good agreement for all examples and figures of the Hopf bifurcations. Examples of limit cycle and phase-plane map are plotted to confirm the benefits and accuracy of semi-analytical solutions result. For periodic solutions, an asymptotic method is studied after the Hopf bifurcation point for both one- and two-term semi-analytical systems.
How far is FDI relevant to India’s foreign trade growth? An empirical investigation
Authors: Jana Shib Sankar , Sahu Tarak Nath , Pandey Krishna Dayal
Published: April 2020

The study seeks to foster fresh empirical evidence on how FDI is relevant to the foreign trade growth in India under a time-varying parameter model with vector autoregressive specification. The Johansen’s cointegration test documents a significant and positive long-run co-movement between FDI and foreign trade in India. The vector error correction model suggests a unidirectional long-run causality from foreign trade to FDI. However, the Granger causality test confirms a bidirectional short-run causal relationship between these variables. Further, the variance decomposition analysis approves strong exogeneity of foreign trade. Again, the impulse response function analysis reveals that the responses generated from a positive shock of foreign trade to FDI and vice versa are small and initially negative and thereafter remain persistently positive at a constant level. The study finally concludes that the absence of long-run causality from FDI to export is the result of much domestic market orientation of foreign investors and less emphasis on the export-oriented sectors in India.
Dual EGFR blockade with cetuximab and erlotinib combined with anti-VEGF antibody bevacizumab in advanced solid tumors: a phase 1 dose escalation triplet combination trial
Authors: Subbiah Vivek , Dumbrava Ecaterina Ileana , Jiang Yunfang , Thein Kyaw Z. , Naing Aung , Hong David S. , Fu Siqing , Piha-Paul Sarina A. , Tsimberidou Apostolia M. , Janku Filip , Meric-Bernstam Funda , Kurzrock Razelle , Falchook Gerald
Published: April 2020

Background

Angiogenesis and activation of the epidermal growth factor (EGFR) pathway play an essential role in tumor proliferation and metastasis. Targeting angiogenesis or EGFR alone does not yield adequate tumor control in most solid tumors. Overcoming intrinsic and/or acquired resistance may need a doublet or triplet therapy strategy. Herein, we report the safety and feasibility of dual EGFR blockade with EGFR monoclonal antibody and EGFR tyrosine kinase inhibitor combined with anti-VEGF antibody in advanced solid tumors.

Methods

We conducted a phase I study combining erlotinib, cetuximab, and bevacizumab. Patients with advanced or metastatic solid tumors (excluding colorectal and non-small cell lung cancers) were analyzed for safety, toxicity profile, and response. Anti-tumor activity was evaluated per response evaluation criteria in solid tumors (RECIST 1.0).

Results

Thirty-six patients received treatment on a range of dose-levels. The most frequent tumor types enrolled were cervical (n = 10), head and neck squamous cell (n = 10), and follicular thyroid (n = 4) cancers. The most common treatment-related grade ≥ 2 adverse events were rash (56%), hypomagnesemia (17%), pruritus (11%), diarrhea (8%), and tumor-related bleeding (8%). Seventeen of 19 patients (89%) treated at the maximum tolerated dose did not present treatment-related dose-limiting toxicity. Fifteen (63%) of the 24 evaluable patients achieved a disease control (stable disease ≥ 4 months (n = 14) and partial response (n = 1). The median number of prior lines of therapies was 3 (range 1–10).

Conclusions

The triplet combination of erlotinib, cetuximab, and bevacizumab was well tolerated, conferring clinical benefit in heavily pretreated patients. Future studies are warranted with second or third-generation EGFR tyrosine kinase triplet combinations in the EGFR pathway aberrant patients.

Trial Registration: ClinicalTrials.gov Identifier: NCT00543504. Sponsor(s): National Cancer Institute (NCI), MD Anderson Cancer Center
Salvator Mundi: an investigation of the painting’s materials and techniques
Authors: Gutman Rieppi Nica , Price Beth A. , Sutherland Ken , Lins Andrew P. , Newman Richard , Wang Peng , Wang Ting , Tague Thomas J.
Published: April 2020

Before the start of its restoration in 2007, the Salvator Mundi was thought to be one of a number of copies of a long-lost Leonardo da Vinci painting, depicting Christ giving a blessing with his right hand while holding a crystal orb in his left. During the restoration treatment, a scientific examination of the painting was carried out to elucidate the painting’s materials and techniques. Microscopic sampling of the painting was necessarily limited, and nine out of ten samples were prepared and analyzed as cross-sections. A number of analytical methods were employed selectively, including stereomicroscopy, visible and fluorescent light microscopy, scanning electron microscopy with energy dispersive spectroscopy, Raman microspectroscopy, Fourier transform infrared microspectroscopy in transmission mode and with attenuated total reflection. The pigments characterized were lead white, vermilion, red iron oxide earth, red lake, natural ultramarine, lead–tin yellow, umber, and charcoal, carbon and bone blacks. Manganese-containing soda-lime glass was detected in the ground, imprimitura and paint layers, and a walnut oil medium was identified by pyrolysis gas chromatography-mass spectrometry. Cross-section studies revealed aspects of the painting’s stratigraphy: a size layer, white ground and off-white imprimitura, followed by a complex sequence of paint layers applied by the artist to achieve sophisticated visual effects.
Bochdalek hernia in an adult: two case reports and a review of perioperative cardiopulmonary complications
Authors: Akita Masayuki , Yamasaki Nobuaki , Miyake Taiichiro , Mimura Kazuya , Maeda Eri , Nishimura Tohru , Abe Koichiro , Kozuki Akihito , Yokoyama Kunio , Kominami Hiroaki , Tanaka Tomohiro , Takamatsu Manabu , Kaneda Kunihiko
Published: April 2020

Background

Bochdalek hernia in an adult is very rare and often needs an immediate surgical repair for the herniation. Although its etiology and surgical techniques have frequently been reported, perioperative complications, especially cardiopulmonary problems, remain unknown. We reported two adults with Bochdalek hernia and reviewed the published literatures with a focus on these issues.

Case presentation

We experienced two adult cases of Bochdalek hernia with gastrointestinal strangulation. One case had massive herniation of the stomach, colon, spleen, and pancreas in the left chest, causing repeated vomiting. The other had a right-side hernia with strangulation of the colon. We successfully performed emergency repairs of these diaphragmatic hernias without any postoperative complications.

Conclusions

Our literature review revealed that life-threatening cardiopulmonary complications, such as empyema or cardiac arrest caused by the tamponade effect of the herniated viscera, sometimes occurred in patients with Bochdalek hernia. These complications were found in Bochdalek hernia with gastrointestinal strangulation.
Free-breathing T2* mapping for MR myocardial iron assessment at 3 T
Authors: Nazarova E. E. , Tereshchenko G. V. , Kupriyanov D. A. , Smetanina N. S. , Novichkova G. A.
Published: April 2020

Background

Timely diagnosis of cardiac iron overload is important for children with transfusion-dependent anaemias and requires modern measure methods. Nowadays, myocardial iron quantification is performed by magnetic resonance (MR) breath-hold techniques, sensitive to respiratory motion and unfeasible in patients who are unable to hold their breath. Free-breathing T2* mapping sequences would allow to scan children who cannot hold their breath for a specified duration. Our aim was to test a free-breathing T2* mapping sequence, based on motion correction by multiple signal accumulation technique.

Methods

We used an electrocardiographically gated T2* mapping sequence based on multiple gradient echo at 3-T in 37 paediatric patients with haematologic disorders aged from 2 to 16. We compared T2* values of myocardium and signal-to-noise ratio of this new sequence with standard breath-holding T2* mapping sequence. T2* values were measured in the interventricular septum for both methods in studies with adequate image quality.

Results

All children were scanned without complications. Five patients were excluded from analysis because of the presence of respiratory artefacts on the T2* images with breath-holding technique due to patient’s inability to hold their breath. Breath-holding T2* was 19.5 ± 7.7 ms (mean ± standard deviation), free-breathing T2* was 19.4 ± 7.6 ms, with positive correlation (r = 0.99, R2 = 0.98; p < 0.001). The free-breathing sequence had a higher signal-to-noise ratio (median 212.8, interquartile range 148.5–566.5) than the breath-holding sequence (112.6, 71.1–334.1) (p = 0.03).

Conclusion

A free-breathing sequence provided accurate measurement of myocardial T2* values in children.
Formulation of Trichoderma asperellum TV190 for biological control of Rhizoctonia solani on corn seedlings
Authors: Herrera Wence , Valbuena Oscar , Pavone-Maniscalco Domenico
Published: April 2020

Environmental conditions affect biocontrol agents in a field, being appropriate formulations an alternative to overcome this problem. Formulations based on Trichoderma asperellum TV190 were prepared by emulsified mineral or vegetable oils, which protected spores from ultraviolet radiation, showing greater viability of 37–43% (mineral) and 56–63% (vegetable) than the control (8–12%). These formulations improved an antagonism of T. asperellum on Rhizoctonia solani under greenhouse conditions, reducing infected corn seedlings by 72% (mineral) and 59% (vegetable). Necrotic spot size was reduced by 90.04% (mineral) and 87.29% (vegetable). A granular formulation, prepared with degreased corn germ and T. asperellum spores, protected the corn seedlings from R. solani under greenhouse conditions, with 73% reduction of infected plants and 93% reduction of necrotic spot size. Both granular and liquid formulations were able to improve T. asperellum antagonism, suggesting that these formulations could be included in agricultural pest control strategies.
Phase II study of erlotinib given daily for patients with metastatic melanoma (MM)
Authors: Wyman K. , Kelley M. , Puzanov I. , Sanders K. , Hubbard F. , Krozely P. , Sturgeon D. , Viar V. , Sosman J. A.
Published: April 2020

18002

Background: Erlotinib is a small molecule tyrosine kinase inhibitor (TKI) that targets epidermal growth factor receptor (EGFr). The EGFr is a potential therapeutic target because it is expressed by a number of malignancies, including melanocytic lesions, and in some plays an important role in the biology of the cancer. Our aim was to conduct a phase II study evaluating erlotinib in patients (pts) with measurable metastatic melanoma. Methods: Eligibility criteria included measurable disease, ECOG PS = 0–1, and adequate organ function. Pts were eligible if they received up to one prior therapy for metastatic disease. Pts received a daily dose of erlotinib 150 mg. The primary outcomes were overall response rate and response duration. The study had a two-stage design with closure at 14 pts if there were no objective RECIST responses. Secondary outcomes included overall safety and tolerability of erlotinib. Results: Between August 2003 and August 2004, a total of 14 pts with MM were accrued. The majority of pts were male 12:2 = M, median age = 57.5 yrs (range 38 to 80 yrs). Stage of disease included M1a (n = 7), M1b (n = 5), M1c (n = 2) and performance status was equally divided between 0 and 1 (7 pts each). Seven pts (50%) had prior adjuvant therapy and six pts (43%) had at least one prior therapy for metastatic disease. Four pts (29%) had no prior therapy. No objective responses were observed. Four pts (29%) had stable disease at their initial 8-week evaluation of which only 2 had SD>6 months (228 and 365 days). One pt with SD withdrew from the study on day 68 for grade II toxicities. There were no Grade III/IV hematological or biochemical toxicities. Grade III toxicities were diarrhea and anorexia, each in a single patient. Most pts (n = 12) experienced at least a grade I dermatological toxicity manifested as an acneiform rash and/or pruritis. The median progression free survival (PFS) of all 14 pts was approximately 60 days with a range of 35 to 365 days. The median PFS of those with SD was 192.5 days. Conclusions: Erlotinib given daily at 150 mg is well tolerated in pts with MM. However, it has minimal to no single agent activity. Any further investigation of this drug should be pursued in combination with other agents only if a strong scientific/clinical rationale exists.

No significant financial relationships to disclose.
DAB(389)IL2 (denileukin diftitox) suppresses growth of melanoma metastases
Authors: Chesney J. , Guarnaschelli J. , Telang S. , Miller D.
Published: April 2020

18010

Background: CD4+CD25high regulatory T (Treg) cells have been found to suppress the activation of anti-tumor effector T cells. Depletion of Treg cells using anti-CD25 antibodies can induce a CD8+ T cell dependent rejection of melanoma in mice. Furthermore, Treg cells are increased in human lymph nodes containing melanoma metastases relative to adjacent benign lymph nodes. Taken together, these observations provide rationale for an examination of the effect of Treg cell depletion on the progression of metastatic melanoma in humans. Recombinant interleukin 2/diphtheria toxin conjugate (DAB[389]IL2; also termed ONTAK or denileukin diftitox) binds to CD25 and, following internalization, causes cell death. DAB(389)IL2 was recently reported to selectively deplete peripheral blood Treg cells in patients with renal cell carcinoma. Methods: The effect of DAB(389)IL2 on tumor growth was examined in 4 patients with Stage IV melanoma who had either progressed after biochemotherapy and/or high dose IL-2 or were ineligible for these treatments. DAB(389)IL2 (9 or 12 μg/kg) was administered daily x 4 days every three weeks for two cycles. FDG-PET/CT imaging was obtained just prior to DAB(389)IL2 administration and within 2 weeks of completion of the second cycle. In the setting of stable disease or tumor regression, DAB(389)IL2 was continued for two more cycles and a subsequent FDG-PET/CT imaging study was obtained. Results: Two patients received 9 μg/kg DAB(389)IL2 and, after two cycles, experienced overt progression consisting of a combination of tumor growth and newly detectable tumors. Two patients received 12 μg/kg DAB(389)IL2 and, after two cycles, experienced a combination of stable disease and marked regression of several metastatic tumors. In one patient, tumor volume of right and left axillary metastases shrunk by 33% and 43%, respectively, after two cycles of DAB(389)IL2. The second responding patient experienced resolution of several dermal metastases, reduction in the tumor volume of a left adrenal mass, and the complete regression of two hepatic metastases. Conclusions: We conclude that DAB(389)IL2 may provide a safe and effective treatment for stage IV melanoma. A phase II clinical trial is now underway to examine the efficacy of DAB(389)IL2 in this patient population.

No significant financial relationships to disclose.
Effect of age on treatment and survival among patients with non-small cell lung cancer
Authors: Owusu O. , Owusu C. , Hankins M.
Published: April 2020

18504

Background: Lung cancer is a disease of the elderly. Yet older patients are underrepresented in clinical trials resulting in scanty efficacy data. We sought to assess the relationship between age, treatment and overall survival in a cohort of patients with non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective cohort study of patients with consecutively diagnosed NSCLC between 1999 and 2003 at the Boston Veterans Administration Medical Center (BVAMC). All patients with a biopsy proven NSCLC were included. Patients diagnosed at autopsy were excluded. Data sources included the BVAMC tumor registry and medical records. Deaths were ascertained from the Social Security Administration and VA databases. All patients were right censored at death from any cause or at 12/31/2004, whichever came first. Our primary endpoints were 1) receipt of surgery; 2) receipt of chemotherapy; and 3) three-year overall survival. Our independent variable was age, operationalized as 70 years and older versus less than 70 years. We used logistic regression analysis to assess the relationship between age and treatment and Kaplan-Meier curves and Cox proportional hazards modeling to determine the effect of age on survival. Results: We studied 410 patients. 211 (51%) of the cohort were ≥70 years and 199 (49%) were <70 years. Among those with localized disease (stages I and II) there was no significant difference in the odds of receiving surgery between the two age categories, (OR = 1.54, 95% CI, 0.72, 3.28). Among those with non-localized disease (stages III and IV) those who were ≥ 70 years were less likely to receive chemotherapy (OR = 0.46, 95% CI, 0.27, 0.79). There were 308 deaths from all causes: 167 in the ≥ 70 year group and 141 in the <70 year group. The three-year overall survival was 20.4% (95% CI, 14.5%, 26.3%) and 32.7% (95% CI, 25.3%, 39.5%) for the ≥70 and <70 year groups, respectively. The adjusted hazard ratio was 0.72 (95% CI, 0.57, 0.92), P = 0.03 by the log rank test in favor of those less than 70 years. Other significant predictors of overall survival included stage at diagnosis and treatment. Comorbidity was not a significant predictor of overall survival. Conclusion: The poorer survival outcome among older NSCLC patients at the BVAMC may be improved by more aggressive treatment with chemotherapy.

No significant financial relationships to disclose.
Evaluation of predictive factors for response to darbepoetin alfa (DA): A prospective study
Authors: Steinmetz H. T. , Fandel F. , Hellmich M. , Neise M. , Aldaud A. , Lerchenmüller C. , Tsamaloukas A. , Weiligmann C. , Schmitz S.
Published: April 2020

18514

Background: Therapy with erythropoiesis-stimulating factors (ESF) can ameliorate the anaemia associated with cancer and chemotherapy, reduce the need for transfusions and improve quality of life. However, as many as 30–50% of pts. do not respond, even to very high doses of ESF. Methods: In January 2003, we commenced a prospective phase-2 study to evaluate the value of predictive factors for response to DA. The following 5 factors, which had been previously determined as predictive factors in several retrospective studies, were investigated: serum erythropoietin < 100 mU/ml before therapy (Epo-d0); increase in reticulocytes > 40,000/μl (Reti-d14) and in soluble transferrin receptor ≥ 25% (sTfR-d14), both after 2 weeks; increase in reticulocytes > 40,000/μl (Reti-d28) and in Hb > 1 g/dl (Hb-d28), both after 4 weeks. Response was defined as Δ Hb > 2 g/dl or Hb ≥ 12 g/dl within 8–12 weeks. Pts. with solid tumours receiving chemotherapy, ECOG < 2 and Hb < 11g/dl or significant decrease in Hb > 1.5 g/dl within 4 weeks received DA 150 μg/QW or 300 μg/Q2W sc. and 300 μg/QW if Hb < 1 g/dl at d28. Results: Between 01/03 and 09/05 196 pts., 112 female and 84 male, median age 66 years, were treated and evaluated for response. 119 pts. (60.7%) had a response as defined (PP analysis: 68.3%). The predictive value of the 5 factors are given in the Table . In a multiple logistic regression analysis of all 5 factors the ROC has an AUC of 0.78 (95% CI 0.71–0.84). The reduced logistic classification rule (with cutoff 0.5) based on an increase in sTfR > 25% on day14, reticulocytes > 40,000/μl and Hb > 1 g/dl, both on day 28, had the same AUC and its positive / negative predictive value was 88.1% (=74/84) and 59.8% (=67/112) respectively. Conclusions: In contrast to observations made in pts. with lymphoproliferative malignancies, the pretherapeutic serum erythropoietin level has no or very little predictive value for response to DA in anaemic pts. with solid tumours. Supported by AMGEN, Germany with an unrestricted grant.

[Table: see text]

[Table: see text]
Depression, immunity, and survival in patients diagnosed with hepatobiliary carcinoma
Authors: Steel J. L. , Geller D. A. , Olek M. C. , Carr B. I.
Published: April 2020

18525

Background: Depression has been found to be associated with increased morbidity and mortality in healthy adults. The prevalence of depression in patients diagnosed with cancer, and in particular hepatobiliary carcinoma (HBC), is significantly higher than the general population. The aims of the present study were to: (1) examine the prevalence of depressive symptoms in patients with HBC, (2) test the relationship between depressive symptoms and survival, and (3) begin to explore underlying mechanisms that explain the relationship between depression and survival in patients with HBC. Methods: 101 patients diagnosed with HBC were administered a battery of questionnaires which included the Center for Epidemiological Studies-Depression (CES-D) questionnaire. Disease-specific data was gathered from medical charts and survival was measured from the date of diagnosis to death. Immune markers (NK cell, IL-4 and 5, TNF, and IFN) were collected in 24 patients. Results: At diagnosis, 39% of the sample reported a score of 16 or greater (clinical range). Using Cox Regression, demographic (age, gender, ethnicity) and disease specific variables (diagnosis, treatment, hepatitis, cirrhosis, tumor location, tumor number, tumor size, vascularity of lesion, and portal vein invasion) variables, as well as CES-D score at diagnosis were analyzed. CES-D scores >16 [Wald = 4.0, p = 0.05] and portal vein invasion (PVI) [Wald = 9.0, p = 0.003] significantly predicted survival. Using Kaplan Meier Survival analysis (Breslow test) and stratifying for PVI, a trend was found [Chi-Square = 3.1, p = 0.08] in which patients with PVI and CES-D scores >16, survived 7.4 months whereas patients with CES-D scores <16 survival 13 months. Patients without PVI and CES-D scores >16 survived 18.2 months whereas those with CES-D scores <16 survived 24.7 months. In a sample of 24 patients, those who reported CES-D scores >16 had significantly lower Natural Killer cell numbers than patients with CES-D scores <16 while covarying age, gender, stress, social support, and coping style [F(1,21) = 9.39, p = 0.003]. Conclusions: Depression may be an important prognostic factor for patients diagnosed with HBC.

No significant financial relationships to disclose.
The most troublesome aspects of quality of life for people with advanced cancer in a supportive care trial
Authors: Nowak A. K.
Published: April 2020

18527

Background: ZEST is a placebo-controlled trial of sertraline for people with advanced cancer who feel depressed, anxious or tired but do not have a clear indication for antidepressants. We describe here the aspects of quality of life (QL) rated most troublesome at baseline by the first 150 subjects. Methods: Subjects completed a battery of QL questionnaires including the CES-D, HADS, FACT-G, FACT-Fatigue, and the Patient Disease and Treatment Assessment Form (Pt DATA Form). The Pt DATA Form assesses pertinent symptoms and concerns using 40 single items with a uniform response scale from 0 (no trouble at all) to 10 (worst I can imagine). Test-retest reliability was assessed with the intraclass correlation coefficient (ICC). Convergent validity was assessed by testing correlations between single items from the PT DATA Form and the corresponding, validated, multi-item scales. Results: The median age was 66 (IQR 59 to 73); median Karnofsky Perfomance Status was 80 (IQR 70 to 90); 63% were male; commonest primaries were colorectal (17%), lung (16%), prostate, (14%), breast (13%), and gynaecologic (10%). The aspects rated worst (mean score, proportion scoring >3) were: Fatigue (5.5, 90%), Problems with sex (4.1, 51%), Trouble sleeping (3.6, 49%), Drowsiness (3.5, 54%), Not feeling myself (3.5, 51%), Pain (3.4, 45%), Shortness of breath (3.4, 47%), Problems doing what I wanted (3.1, 45%), Anxiety (3.0, 40%), Depression (2.7, 36%), Dry mouth (2.7, 38%), Trouble concentrating (2.7, 30%), Irritability (2.6, 32%), Altered sense of taste (2.5, 34%), Difficulty walking (2.4, 32%), and Constipation (2.1, 24%). Mean scores were higher in men than women for Problems with sex (5.0 v 2.4, p < 0.001); and, in subjects aged 65 or younger for Hair loss (2.4 v 1.1, p = .01). There were no other significant differences by gender or age. Correlations supported the validity of the single item scales for depression, anxiety, fatigue; and for physical, emotional and overall well-being. The test-retest reliability of the Pt DATA Form was good (ICC >0.5 for 34 of 40 items). Conclusions: Pertinent aspects of QL were validly measured with single item scales. Insomnia, dry mouth, altered sense of taste and irritability were more troublesome than many other, better studied symptoms.

No significant financial relationships to disclose.
Tumor-specific response rates to erythropoietin in chemotherapy-induced anemia in a community practice setting
Authors: Vasu S. , Seidler C. , Field T. , Emani S.
Published: April 2020

18528

Background: Erythropoietin [Epo] is widely used in the management of Chemotherapy-Induced Anemia [CIA] with reported response rates of 70% in the setting of clinical trials. To evaluate overall response rates and tumor specific response rates a retrospective study was performed. Methods: Chart reviews of 109 consecutive patients with chemotherapy-induced anemia were conducted from 2001–2004. Inclusion criteria were: age > 18 yrs, solid or non-myeloid hematological malignancy, receiving concurrent chemotherapy. Patients who received at least one dose of epo were also included, under the intention-to-treat principle. Hb, HCT and MCV during the course of chemotherapy and epo treatment were also collected. Transfusion requirements were also noted. Rise of 1gm Hb after receiving at least 8 weeks of epo was considered as evidence of responsiveness. Epoetin alpha was administered as 40,000 units weekly or darbepoietin at 200mcg q2 weeks and appropriate dose adjustments were made depending on responses. A PRBC transfusion after Day 29 was considered to be evidence of non-responsiveness. Results: Of 109 patients, 108 were considered eligible to be studied. The table shows the distribution of patients according to cancer type. Among the patients who received epo for 8 weeks, the epo response rate was 46%. 21 patients required transfusions after Day 29. Conclusions: Our data suggests that the community response rates to erythropoietin are lower than that reported in the literature. Tumor specific response rates were not statistically significantly (p > 0.05), although this may reflect the small number of patients in the study. A multivariate analysis is being performed to determine if there are predictive factors for response.

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Ondansetron (O) with or without dexamethasone (D) for the prevention of chemotherapy (C)-induced nausea and vomiting (CINV)
Authors: Bonicatto S. , Mainella A. , Troncoso E. , Barbero A. , Lavezzaro M. , Zapata G.
Published: April 2020

18558

Background: Adition of D to the standard antiemetic treatment for CINV prevention is frequent, despite the lack of benefit evidence in controlled clinical trials. In this study we compare the impact of O treatment with or without D on daily life, in patients (pts) under treatment with high or moderately emetogenic C. Methods: Longitudinal, randomized and prospective study. All pts who received anticancer treatment with high or moderately emetogenic C were included, and randomly assigned to group A (O 8 mg iv and D 8 mg iv) or group B (O 8 mg iv). Evaluable pts did not have to receive any medication which could modify the antiemetic effect of treatment within the 24 hours following the administration of CH and had to be able to answer an autoadministered questionnaire. After 24 hours, the Functional Living Index- Emesis (FLIE), a daily life index which consists of 18 questions divided into two domains: nausea and vomiting, had to be completed. Data were analyzed by independent mean sample t-test, and ANOVA One-Way, with a 0.05 significance level. Results: Between December/04 and November/05 233 patients (age average: 59.24; range 21–87) were randomly assigned to antiemetic treatment with (n = 125) or without D (n = 108). Both groups were well balanced as regards the type of chemotherapy, sex and age, and all patients were evaluable. No significant effects were observed between both groups when the global data were analyzed. However, when the sample was stratified by type of chemotherapy, a significantly lower impairment (55.1 vs 51.3; p < .05) was detected in the nausea domain in those patients who received moderately emetogenic chemotherapy. Conclusion: In our sample of patients we observed benefits in the impact on daily life, by the addition of D to the O as preventive treatment of CINV, in those patients that received moderately emetogenic chemotherapy.

No significant financial relationships to disclose.
Health related quality of life (HRQoL) and demographic characteristics of long term head and neck cancer survivors submitted to concomitant chemoradiation in Brazil
Authors: Santos D. V. , Kiyota K. M. , Snitcovsky I. , Leitão G. M. , Federico M. H.
Published: April 2020

18572

Background: Head and neck cancer (HNC) is a stigmatizing disease. In order to identify special needs in these patients (pts), we evaluated HRQoL and the demographic characteristics of HNC pts who had survived at least one year after chemoradiation. Methods: Our survey, done in may 2005, identified 42 pts alive (from 527 admitted from May 2002 to May 2004 treated with either exclusive (n = 19) or adjuvant (n = 23) chemoradiation. These pts as well 16 normal controls, were interviewed and invited to complete EORTC-QLQ-C30 and HN35. These questionnaires had already been validated for Brazilian Portuguese. Primary site was 12 oral cavity, 14 pharynx, 13 larynx, 3 not determined. Age 60.3 ± 9.0 y, 36 male and 6 female; 39 were squamous cell carcinoma and 3 other type; 28 were stage III or IV; 40 had no evidence of disease and two had recurrent disease at the time of survey. Comparison between groups were done by using the Mann-Whitney test and differences of at least 10 points was considered of clinical significance. Simple correlations were conducted between HRQoL variables and clinical correlates and demographics. The level of significance was established at p < 0.05. This work was conducted according to Helsinki declaration and Brazilian law. Results: Scores relative to global QoL (p = 0.18) and emotional function (p = 0.59) did not differ in pts as compared to controls. Pts presented worse scores in swallowing, senses, speech, pain, dental problems, xerostomia and mouth opening (all p < 0.05). Emotional function (r = 0.316, p = 0.041) and financial worries (r = −0.509, p = 0.001) impacted on global QoL, what did not happen with marital status, income and level of education, age or previous surgery. Chronic pain was more prevalent in oral cavity tumors than in other sites such as pharynx or larynx tumors (p = 0.046 and p = 0.030, respectively). Pts with larynx tumors presented worse cough score as compared to those with pharynx tumors (p = 0.009). Conclusions: Providing continuous oral and dental care seems to be important to address survivors’ concerns. Financial distress could be ameliorated by a better social support system. Tumor site seem to affect differently some domains of HRQoL, in contrast to organ preservation.

No significant financial relationships to disclose.
Assessment of nutritional status and prognosis in advanced metastatic cancer (AMC) of gastrointestine (GI)
Authors: Choi K. , Kim H. J. , Cho H. J. , Oh S. J. , Lee S. S.
Published: April 2020

18573

Background: Depletion of nutritional reserves and significant weight loss can lead to an increased risk of morbidity, reduced chemotherapy response, and shorter survival in patients (pts) with cancer. Numerous methodologies are used for the assessment of nutritional status. However, it remains unclear which of these tools is the most appropriate in the setting of cancer chemotherapy. The PINI (prognostic inflammatory nutritional index) is a simple scoring system that has been used to evaluate nutritional status and prognosis in critically ill pts. The aim of this study was designed to investigate the relationship between nutritional status after the palliative chemotherapy and prognosis in AMC of GI. Methods: This study included 130 pts with ECOG PS 1∼3 in AMC of GI following the palliative chemotherapy. ECOG PS, body mass index (BMI), alpha 1-acid glycoprotein (AGP), C-reactive protein (CRP), albumin (ALB), prealbumin (PALB), transferrin, protein, lactate dehydrogenase (LDH), PINI ratio [PINI = (AGP × CRP)/(ALB × PALB)], and survival time were evaluated. Results: In 130 patients, the median age was 57 years. The ECOG PS was 1: 68 patients, 2: 43 patients, 3: 19 patients. The mean value of PINI was PS 1: 16.0 ± 47.8, PS 2: 55.6 ± 106.9, PS 3: 106.3 ± 141.6. The mean survival was PS 1: 144.0 ± 71.8, PS 2: 68.9 ± 41.2, PS 3: 32.0 ± 6.9 days. In the PS 3 group, the mean values of AGP, CRP, and LDH were significantly higher than in the PS 1 group. In the PS 3 group, the mean values of ALB, PALB, and transferrin were significantly lower than in the PS 1 group. The survival time was correlated with the ECOG PS (r = −0.602, p < 0.001,), PINI (r = −0.318, p < 0.001,), AGP (r = −0.265, p = 0.002), CRP (r = −0.345, p < 0.001), ALB (r = 0.324, p < 0.001), PALB (r = 0.260, p = 0.003) and transferrin (r = 0.377, p = 0.001). Conclusions: The PINI should be considered nutritional status and prediction of prognosis in AMC of GI following palliative chemotherapy.

[Table: see text]

No significant financial relationships to disclose.