bluuebunny/crossref_metadata_2025 huggingface dataset:
CD4+ T cell expression of the IL-10 receptor is necessary for facial motoneuron survival after axotomy
Authors: Runge Elizabeth M. , Iyer Abhirami K. , Setter Deborah O. , Kennedy Felicia M. , Sanders Virginia M. , Jones Kathryn J.
Published: April 2020

Background

After peripheral nerve transection, facial motoneuron (FMN) survival depends on an intact CD4+ T cell population and a central source of interleukin-10 (IL-10). However, it has not been determined previously whether CD4+ T cells participate in the central neuroprotective IL-10 cascade after facial nerve axotomy (FNA).

Methods

Immunohistochemical labeling of CD4+ T cells, pontine vasculature, and central microglia was used to determine whether CD4+ T cells cross the blood-brain barrier and enter the facial motor nucleus (FMNuc) after FNA. The importance of IL-10 signaling in CD4+ T cells was assessed by performing adoptive transfer of IL-10 receptor beta (IL-10RB)-deficient CD4+ T cells into immunodeficient mice prior to injury. Histology and qPCR were utilized to determine the impact of IL-10RB-deficient T cells on FMN survival and central gene expression after FNA. Flow cytometry was used to determine whether IL-10 signaling in T cells was necessary for their differentiation into neuroprotective subsets.

Results

CD4+ T cells were capable of crossing the blood-brain barrier and associating with reactive microglial nodules in the axotomized FMNuc. Full induction of central IL-10R gene expression after FNA was dependent on CD4+ T cells, regardless of their own IL-10R signaling capability. Surprisingly, CD4+ T cells lacking IL-10RB were incapable of mediating neuroprotection after axotomy and promoted increased central expression of genes associated with microglial activation, antigen presentation, T cell co-stimulation, and complement deposition. There was reduced differentiation of IL-10RB-deficient CD4+ T cells into regulatory CD4+ T cells in vitro.

Conclusions

These findings support the interdependence of IL-10- and CD4+ T cell-mediated mechanisms of neuroprotection after axotomy. CD4+ T cells may potentiate central responsiveness to IL-10, while IL-10 signaling within CD4+ T cells is necessary for their ability to rescue axotomized motoneuron survival. We propose that loss of IL-10 signaling in CD4+ T cells promotes non-neuroprotective autoimmunity after FNA.
Infant feeding guideline awareness among mothers living with HIV in North America and Nigeria
Authors: Phillips J. Craig , Etowa Josephine , Hannan Jean , Etowa Egbe B. , Babatunde Seye
Published: April 2020

Background

WHO guidelines recommend breastfeeding for mothers living with HIV adherent to antiretroviral therapy in countries where formula is not accessible. In Canada and the US, guidelines for mothers living with HIV recommend exclusive formula feeding. Awareness of national infant feeding guidelines and socio-cultural factors influence infant feeding choices that may result in an increased risk of vertical transmission of HIV. The purpose of this paper is to present factors associated with awareness of guidelines among Black mothers living with HIV. Data were derived from a survey conducted as part of a recent international study that examined infant feeding practices among Black women living with HIV in Ottawa, Canada; Port Harcourt, Nigeria; and Miami, Florida.

Methods

Participants (n = 690) from Port Harcourt (n = 400), Miami (n = 201), and Ottawa (n = 89) were surveyed on their awareness of infant feeding guidelines for mothers living with HIV. Data were collected between November, 2016 and March, 2018.

Results

Participants’ mean ages were 34.3 ± 5.9 years. Across all sites, 15.4% (95% CI 13.2, 7.7) of mothers were NOT aware of their country’s infant feeding guidelines. Cultural beliefs (OR = 0.133, p = 0.004, 95% CI 0.03, 0.53) and functional social support influenced infant feeding choices (OR = 1.1, p = 0.034, 95% CI 1.01, 1.20) and were statistically significant predictors of guideline awareness (Χ2 = 38.872, p < .05) after controlling for age, years of formal education, marital status, and country of residence. As agents of functional social support, family members and health workers (e.g., nurses, physicians, social workers, other health care workers) influenced participants’ awareness of infant feeding guidelines and guided them in their infant feeding choices.

Conclusions

Among participants, awareness of national infant feeding guidelines was associated with functional social support and cultural beliefs influenced infant feeding choices. Therefore, culturally adapted messaging via social supports already identified by mothers, including family relationships and health workers, is an appropriate way to enhance awareness of infant feeding guidelines. Ultimately, contributing to the global health goals of maternal health and reduced infant mortality.
Prenatal infant feeding intentions and actual feeding practices during the first six months postpartum in rural Rwanda: a qualitative, longitudinal cohort study
Authors: Ahishakiye Jeanine , Bouwman Laura , Brouwer Inge D. , Vaandrager Lenneke , Koelen Maria
Published: April 2020

Background

Exclusive breastfeeding (EBF) is advocated by the WHO for the first 6 months. In Rwanda, the percentage of infants who are exclusively breastfed decreases from 94% among infants aged 0–1 month to 81% among those aged 4–5 months. Little is known about what influences mothers’ breastfeeding practices. This study aimed to gain insights into expectant mothers’ prenatal feeding intentions, the underlying reasons, actual practices after birth, and factors facilitating or impeding EBF for the first 6 months of a child’s life in Muhanga District, Rwanda.

Methods

This qualitative longitudinal study, conducted between December 2016 and October 2017 as part of a larger study, recruited a purposive sample of 39 pregnant women attending prenatal consultations during their last trimester in two rural health centers. Women were interviewed during pregnancy, within the first week after birth and at 4 and 6 months postpartum to explore intentions, actual practices, critical transition points, and facilitating or impeding factors. Interviews were recorded, transcribed verbatim, and analyzed thematically.

Results

Of the 39 participants, 38 intended to breastfeed within the first hour after birth, and 32 intended to breastfeed exclusively for the first 6 months. In practice, 34 initiated breastfeeding within the first hour, and 12 breastfed exclusively for 6 months. Impeding factors include perceived breastmilk insufficiency, pressure from family members, past experiences, mothers’ concerns over their infants’ health, mothers’ heavy workload, poverty and food insecurity. Factors facilitating early initiation and EBF include mothers’ awareness of EBF’s advantages, confidence in their breastfeeding ability, and support from health professionals and family members.

Conclusion

Despite participants’ intentions about breastfeeding, there was a gap between intentions and actual practices. An interplay of barriers at individual, group and societal levels impeded women from EBF for the first 6 months. EBF promotion interventions should consider supporting and equipping breastfeeding mothers with skills to deal with perceived breastmilk insufficiency and to recognize the true signs of baby hunger cues. Furthermore, important influential family and community members should be targeted to support mothers to breastfeed. Interventions that consider addressing the issue of poverty-driven food insecurity should not be overlooked either.
Biomechanical study of C1 posterior arch crossing screw and C2 lamina screw fixations for atlantoaxial joint instability
Authors: Liu Chuang , Kamara Allieu , Yan Yunhui
Published: April 2020

Background

The biomechanics of C1 posterior arch screw and C2 vertebral lamina screw techniques has not been well studied, and the biomechanical performance of the constructs cannot be explained only by cadaver testing.

Methods

From computed tomography images, a nonlinear intact three-dimensional C1-2 finite element model was developed and validated. And on this basis, models for the odontoid fractures and the three posterior internal fixation techniques were developed. The range of motion (ROM) and stress distribution of the implants were analyzed and compared under flexion, extension, lateral bending, and axial rotation.

Results

All three kinds of fixation techniques completely restricted the range of motion (ROM) at the C1-2 operative level. The C1-2 pedicle screw fixation technique showed lower and stable stress peak on implants. The C1 posterior arch screw + C2 pedicle screw and C1 pedicle screw + C2 lamina screw fixation techniques showed higher stress peaks on implants in extension, lateral bending, and axial rotation.

Conclusions

As asymmetrical fixations, C1 posterior arch screw + C2 pedicle screw and C1 pedicle screw + C2 lamina screw fixations may offer better stability in lateral bending and axial rotation, but symmetrical fixation C1-2 pedicle screw can put the implants in a position of mechanical advantage.
Epidemiology of rheumatoid arthritis in sub-Saharan Africa: a systematic review and meta-analysis protocol
Authors: Essouma Mickael , Nkeck Jan René , Endomba Francky Teddy , Bigna Jean Joel , Ralandison Stéphane
Published: April 2020

Background

So far, only one meta-analysis has estimated the prevalence of rheumatoid arthritis (RA) in Africa. Out of 10 studies included in that meta-analysis, nine came from sub-Saharan African countries and had been published between 1968 and 1988. We will conduct a new systematic review and meta-analysis to update their estimates and provide more consistent prevalence data on RA in sub-Saharan Africa.

Methods

We will comprehensively search electronic databases to select observational studies addressing RA in sub-Saharan Africa and published as from 1 January 2000: PubMed, EMBASE, African Journals Online, Web of Science, and Global Index Medicus. Summary estimates will be derived through random-effects meta-analysis whenever possible. Alternatively, estimates will be reported through narrative synthesis when the random-effects meta-analysis will be impossible. The risk of bias will be assessed using standard methods.

Discussion

This systematic review and meta-analysis shall quantify the magnitude of RA morbidity and mortality in sub-Saharan Africa. Results from this review will be disseminated in peer-reviewed journals, conferences and on social media platforms.

Systematic review registration

PROSPERO CRD42020153483
Protocol for a systematic review of self-management interventions for older adults living with cancer
Authors: Haase Kristen R. , Puts Martine , Sattar Schroder , Gray Mikaela , Kenis Cindy , Donison Valentina , Hall Steven , McLean Bianca , Wills Aria , Howell Doris
Published: April 2020

Background

Cancer predominates in adults over age 65. Cancer treatments are known to create physical and psychosocial challenges, which may be amplified for older adults with cancer.

Learning and applying self-management behaviours and skills during treatment with cancer can help to manage/recover health and improve quality of life. In many other chronic illnesses, self-management interventions are known to improve health outcomes and lower healthcare costs. The purpose of this systematic review is to determine the effectiveness of self-management interventions for older adults with cancer on physical, psychosocial, and health system-related outcomes.

Methods

We are conducting a systematic review of self-management interventions for older adults (65+) diagnosed with cancer (solid tumour or haematological) in the active treatment phase of cancer. This systematic review is guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Studies are limited to experimental or quasi-experimental methods published in English, French, German, or Dutch. A search strategy was designed with a Health Sciences librarian and performed using the following electronic databases: Ageline, AMED, ASSIA, Cinahl, Cochrane, Embase, Medline, PsychINFO, and Sociological Abstracts. Approximately 14,000 titles and abstracts are being electronically screened by a minimum of 2 reviewers, with relevant studies to be screened for full text. The final sample of included studies will be assessed for quality using the Cochrane Risk of Bias tool and Down and Black for quasi-experimental studies, with data synthesized in a narrative and tabular format.

Discussion

This systematic review will expand the knowledge base of interventions supporting self-management for older adults with cancer. This study will inform future intervention development by identifying gaps and strengths in effective self-management interventions targeting the needs of older adults receiving active treatment for cancer.

Systematic review registration

PROPERO registry ID# CRD42019134113
Relative transmissibility of shigellosis among male and female individuals: a modeling study in Hubei Province, China
Authors: Zhao Ze-Yu , Chen Qi , Zhao Bin , Hannah Mikah Ngwanguong , Wang Ning , Wang Yu-Xin , Xuan Xian-Fa , Rui Jia , Chu Mei-Jie , Yu Shan-Shan , Wang Yao , Liu Xing-Chun , An Ran , Pan Li-Li , Chiang Yi-Chen , Su Yan-Hua , Zhao Ben-Hua , Chen Tian-Mu
Published: April 2020

Background

Developing countries exhibit a high disease burden from shigellosis. Owing to the different incidences in males and females, this study aims to analyze the features involved in the transmission of shigellosis among male (subscriptm) and female (subscriptf) individuals using a newly developed sex-based model.

Methods

The data of reported shigellosis cases were collected from the China Information System for Disease Control and Prevention in Hubei Province from 2005 to 2017. A sex-based Susceptible–Exposed–Infectious/Asymptomatic–Recovered (SEIAR) model was applied to explore the dataset, and a sex-age-based SEIAR model was applied in 2010 to explore the sex- and age-specific transmissions.

Results

From 2005 to 2017, 130 770 shigellosis cases (including 73 981 male and 56 789 female cases) were reported in Hubei Province. The SEIAR model exhibited a significant fitting effect with the shigellosis data (P <  0.001). The median values of the shigellosis transmission were 2.3225 × 108forSARmm(secondary attack rate from male to male), 2.5729 × 108forSARmf, 2.7630 × 10-8forSARfm, and 2.1061 × 10-8forSARff. The top five mean values of the transmission relative rate in 2010 (where the subscript 1 was defined as male and age ≤ 5 years, 2 was male and age 6 to 59 years, 3 was male and age ≥ 60 years, 4 was female and age ≤ 5 years, 5 was female and age 6 to 59 years, and 6 was male and age ≥ 60 years) were 5.76 × 10-8forβ61, 5.32 × 10-8forβ31, 4.01 × 10-8forβ34, 7.52 × 10-9forβ62, and 6.04 × 10-9forβ64.

Conclusions

The transmissibility of shigellosis differed among male and female individuals. The transmissibility between the genders was higher than that within the genders, particularly female-to-male transmission. The most important route in children (age ≤ 5 years) was transmission from the elderly (age ≥ 60 years). Therefore, the greatest interventions should be applied in females and the elderly.
Simultaneous detection of EGFR amplification and EGFRvIII variant using digital PCR-based method in glioblastoma
Authors: Fontanilles Maxime , Marguet Florent , Ruminy Philippe , Basset Carole , Noel Adrien , Beaussire Ludivine , Viennot Mathieu , Viailly Pierre-Julien , Cassinari Kevin , Chambon Pascal , Richard Doriane , Alexandru Cristina , Tennevet Isabelle , Langlois Olivier , Di Fiore Frédéric , Laquerrière Annie , Clatot Florian , Sarafan-Vasseur Nasrin
Published: April 2020

Epidermal growth factor receptor (EGFR) amplification and EGFR variant III (EGFRvIII, deletion of exons 2–7) are of clinical interest for glioblastoma. The aim was to develop a digital PCR (dPCR)-based method using locked nucleic acid (LNA)-based hydrolysis probes, allowing the simultaneous detection of the EGFR amplification and EGFRvIII variant. Sixty-two patients were included. An exploratory cohort (n = 19) was used to develop the dPCR assay using three selected amplicons within the EGFR gene, targeting intron 1 (EGFR1), junction of exon 3 and intron 3 (EGFR2) and intron 22 (EGFR3). The copy number of EGFR was estimated by the relative quantification of EGFR1, EGFR2 and EGFR3 amplicon droplets compared to the droplets of a reference gene. EGFRvIII was identified by comparing the copy number of the EGFR2 amplicon to either the EGFR1 or EGFR3 amplicon. dPCR results were compared to fluorescence in situ hybridization (FISH) and next-generation sequencing for amplification; and to RT-PCR-based method for EGFRvIII. The dPCR assay was then tested in a validation cohort (n = 43). A total of 8/19 EGFR-amplified and 5/19 EGFRvIII-positive tumors were identified in the exploratory cohort. Compared to FISH, the EGFR3 dPCR assay detected all EGFR-amplified tumors (8/8, 100%) and had the highest concordance with the copy number estimation by NGS. The concordance between RT-PCR and dPCR was also 100% for detecting EGFRvIII using an absolute difference of 10.8 for the copy number between EGFR2 and EGFR3 probes. In the validation cohort, the sensitivity and specificity of dPCR using EGFR3 probes were 100% for the EGFR amplification detection compared to FISH (19/19). EGFRvIII was detected by dPCR in 8 EGFR-amplified patients and confirmed by RT-PCR. Compared to FISH, the EGFR2/EGFR3 dPCR assay was estimated with a one-half cost value. These results highlight that dPCR allowed the simultaneous detection of EGFR amplification and EGFRvIII for glioblastoma.
Characterising cellular and molecular features of human peripheral nerve degeneration
Authors: Wilcox Matthew B. , Laranjeira Simão G , Eriksson Tuula M. , Jessen Kristjan R. , Mirsky Rhona , Quick Tom J. , Phillips James B.
Published: April 2020

Nerve regeneration is a key biological process in those recovering from neural trauma. From animal models it is known that the regenerative capacity of the peripheral nervous system (PNS) relies heavily on the remarkable ability of Schwann cells to undergo a phenotypic shift from a myelinating phenotype to one that is supportive of neural regeneration. In rodents, a great deal is known about the molecules that control this process, such as the transcription factors c-Jun and early growth response protein 2 (EGR2/KROX20), or mark the cells and cellular changes involved, including SOX10 and P75 neurotrophin receptor (p75NTR). However, ethical and practical challenges associated with studying human nerve injury have meant that little is known about human nerve regeneration.

The present study addresses this issue, analysing 34 denervated and five healthy nerve samples from 27 patients retrieved during reconstructive nerve procedures. Using immunohistochemistry and Real-Time quantitative Polymerase Chain Reaction (RT-qPCR), the expression of SOX10, c-Jun, p75NTR and EGR2 was assessed in denervated samples and compared to healthy nerve. Nonparametric smoothing linear regression was implemented to better visualise trends in the expression of these markers across denervated samples.

It was found, first, that two major genes associated with repair Schwann cells in rodents, c-Jun and p75NTR, are also up-regulated in acutely injured human nerves, while the myelin associated transcription factor EGR2 is down-regulated, observations that encourage the view that rodent models are relevant for learning about human nerve injury. Second, as in rodents, the expression of c-Jun and p75NTR declines during long-term denervation. In rodents, diminishing c-Jun and p75NTR levels mark the general deterioration of repair cells during chronic denervation, a process thought to be a major obstacle to effective nerve repair. The down-regulation of c-Jun and p75NTR reported here provides the first molecular evidence that also in humans, repair cells deteriorate during chronic denervation.
Analgesic, anti-inflammatory and antipyretic activities of ethanolic extract of stem bark of Anogeissus latifolia Roxb
Authors: Sharma Vikas Chandra , Kaushik Atul , Dey Yadu Nandan , Srivastava Bhavana , Wanjari Manish , Jaiswal Bhagat
Published: April 2020

Background

Stem bark ofAnogeissus latifoliaRoxb (family: Combretaceae) is used traditionally and ethnomedicinally to alleviate pain, inflammation and fever conditions. The current study investigates the analgesic, anti-inflammatory and antipyretic activities of ethanolic extract of stem bark ofAnogeissus latifoliaRoxb.

Method

The HPLC studies were carried out to standardize the stem bark ethanolic extract ofAnogeissus latifolia(ALEE) using ellagic acid as a marker. ALEE was screened for analgesic (formalin-induced pain and acetic acid induced writhing) and anti-inflammatory (formalin and carrageenan-induced paw oedema) activities in Wistar rats. Before 1 h of acetic acid or formalin or carrageenan injection, rats were orally fed with ALEE (100, 200 and 400 mg/kg), Aspirin (100 mg/kg) or Indomethacin (10 mg/kg). Antipyretic effect was studied in brewer’s yeast-induced pyrexia model in rats using Paracetamol (100 mg/kg) as a standard drug.

Results

HPLC analysis of ALEE revealed the presence of ellagic acid. ALEE treatment (200 and 400 mg/kg) significantly inhibited pain response in both models. ALEE treatments prevented the raise of paw volume in both in-vivo models with percent inhibition of 44.40 and 46.21, respectively at 5 h. ALEE also showed a significant reduction of yeast-induced pyrexia till 4 h of treatment.

Conclusion

ALEE exhibited analgesic, anti-inflammatory and antipyretic property in experimental models and validates traditional use of ALEE in pain, inflammation and fever.
“PROUD to have been involved”: an evaluation of participant and community involvement in the PROUD HIV prevention trial
Authors: Gafos Mitzy , South Annabelle , Hanley Bec , Brodnicki Elizabeth , Hodson Matthew , McCormack Sheena , Witzel T. Charles , Harbottle Justin , Vale Claire
Published: April 2020

Background

The PROUD trial, a HIV prevention trial in men who have sex with men and trans women, set out to involve community representatives and trial participants in several ways. PROUD also aimed to evaluate participant involvement, to learn lessons and make recommendations for future clinical trials.

Methods

Two structured surveys, one of participant and community representatives involved in the PROUD study, and the other of researchers from the PROUD team, were carried out in 2017. The results from the surveys were reviewed quantitatively and qualitatively, and themes emerging from the data identified and synthesised.

Results

Survey invitations were sent to 88 involved participants, 11 community representatives and 10 researchers. The overall response rate was 55% (60/109). Overall, participants were younger than community representatives, and the majority were from Greater London. As expected, participants were predominantly involved in participant involvement meetings and community representatives in management committees.

Participants and community representatives cited different motivations for getting involved in PROUD. Overall, participants were positive about their involvement; only two participants rated their experience unfavourably. Community representatives were also broadly positive. Most participants and all community representatives felt their involvement made a difference to the trial, themselves and / or the organisations they represented. However, some participant answers reflected the impact of participation in the trial rather than involvement in PPI activities.

Researchers felt that PPI had positive impact across the entire trial cycle. Half felt they would have liked there to have been more PPI activity in PROUD. Researchers noted some challenges and recommendations for the future, including need for adequate funding, more engagement in PPI by all researchers, the need for PPI expertise to facilitate involvement activities and training and mentoring in PPI.

Conclusions

Involving clinical trial participants and wider community representatives as active partners in PPI is feasible and valuable in trials. Researchers are encouraged to consider and appropriately resource participant involvement and prospectively evaluate all PPI within their trials.
Deep learning detection and quantification of pneumothorax in heterogeneous routine chest computed tomography
Authors: Röhrich Sebastian , Schlegl Thomas , Bardach Constanze , Prosch Helmut , Langs Georg
Published: April 2020

Background

Automatically detecting and quantifying pneumothorax on chest computed tomography (CT) may impact clinical decision-making. Machine learning methods published so far struggle with the heterogeneity of technical parameters and the presence of additional pathologies, highlighting the importance of stable algorithms.

Methods

A deep residual UNet was developed and evaluated for automated, volume-level pneumothorax grading (i.e., labelling a volume whether a pneumothorax was present or not), and pixel-level classification (i.e., segmentation and quantification of pneumothorax), on a retrospective series of routine chest CT data. Ground truth annotations were provided by radiologists. The fully automated pixel-level pneumothorax segmentation method was trained using 43 chest CT scans and evaluated on 9 chest CT scans with pixel-level annotation basis and 567 chest CT scans on a volume-level basis.

Results

This method achieved a receiver operating characteristic area under the curve (AUC) of 0.98, an average precision of 0.97, and a Dice similarity coefficient (DSC) of 0.94. This segmentation performance resulted to be similar to the inter-rater segmentation accuracy of two radiologists, who achieved a DSC of 0.92. The comparison of manual and automated pneumothorax quantification yielded a Pearson correlation coefficient of 0.996. The volume-level pneumothorax grading accuracy was evaluated on 567 chest CT scans and yielded an AUC of 0.98 and an average precision of 0.95.

Conclusions

We proposed a deep learning method for the detection and quantification of pneumothorax in heterogeneous routine clinical data that may facilitate the automated triage of urgent examinations and enable treatment decision support.
Presence of VEGF-R3 in the serum of metastatic malignant melanoma patients: Relationship with clinicobiological parameters
Authors: Mouawad R. , Meric J. , Spano J. , Khayat D. , Auclerc G. , Rixe O. , Soubrane C.
Published: April 2020

18004

Background: The presence of metastases is a strong indicator of poor survival in many types of cancer. It has recently been shown that vascular endothelial growth factor-C (VEGF-C), and its receptor Flt-4 (VEGF-R3) are increased in a variety of tumours and may play a pivotal role in the promotion of metastasis. We previously demonstrated that high soluble VEGF-C level was correlated to high tumor burden. Objectives: This study was designed to i) detect and evaluate whether soluble VEGF-R3 play a role in metastatic malignant melanoma patients ii) to determine if they have any relationship with clinicobiological parameters, clinical response and survivals. Methods: Using a sensitive enzyme-linked immunosorbent assays, VEGF-R3 was retrospectively measured in sera of 60 patients with a fully documented history of melanoma disease in comparison with 30 healthy controls. Disease free survival (DFS) and overall survival (OS) were calculated from the beginning of treatment until either the progression (DFS) or death (OS) and analyzed using the Kaplan-Meier method. Results: Pretreatment circulating VEGF-R3 was detectable in all samples from either melanoma patients or healthy donors. Furthermore, median level of sVEGF-R3 was significantly higher (p = 0.000015) in melanoma patients as compared to healthy donors. (38890 vs 30773 pg/ml respectively). No significant association was noted between sVEGF-R3 levels and gender, age or LDH level. Median serum VEGF-R3 level was significantly higher in patients with high tumor burden as compared to patients with low tumor burden (p = 0.045). The pretreatment sVEGF-R3 level was significantly different (p = 0.025) between responder (n = 27) and non-responding patients (n = 33). Lastly, the relapse-free survival was higher in the group with low sVEGF-R3 concentration compared to the high one’s (14.1 vs 11,9 months) as well as for OS (14.3 Vs 12.6 months) but theses differences were not significant (χ2 = 2,30, p = 0.12 & χ2 = 0.74, p = 0.37 respectively). Conclusion: these results suggest that high pretreatment sVEGF-R3 level is related to bad prognosis in melanoma patients.

No significant financial relationships to disclose.
Health-care utilization and cost for the treatment of melanoma in the six months following diagnosis
Authors: Taylor D. C. , Zhou Z. , Haider S. , Thompson D.
Published: April 2020

18005

Background: The objective of this study was to use a 5% sample of Medicare claims data to estimate health-care utilization and cost for the treatment of melanoma. Methods: Data for this study were obtained from national administrative Medicare files. Adult patients were selected for the analysis if they were newly diagnosed with melanoma between July 1, 1999 and June 30, 2001. Patients with diagnoses of other cancers prior to melanoma as well as those who did not have data available for at least six months of continuous follow-up were excluded from the analysis. Patients were identified as having Stage 0-II or Stage III-IV melanoma based on the absence or receipt, respectively, of lymph node dissection, chemotherapy, and/or radiation therapy. Study measures included the type, cost, and duration of melanoma treatment. Results: A total of 1,465 patients were identified for the study, including 1,291 with Stage 0-II melanoma and 174 with Stage III-IV melanoma. The mean age was 73.9 years, 54% were female. Overall, 98.3% of patients underwent a surgical procedure, 3.1% underwent chemotherapy, 2.3% had inpatient treatment, 1.2% received radiation, and 1.5% had home health treatment for melanoma in the first six months after diagnosis. Corresponding percentages by disease stage were 100%, 0%, 1.2%, 0%, and 0.9% for Stage 0-II patients, and 85.6%, 25.9%, 10.9%, 10.3%, and 6.3% for Stage III-IV patients. The average total six-month Medicare cost of care was $2,395 ($2,065 outpatient, $330 inpatient) per patient; the average per-patient cost of care was $1,402 ($1,292 outpatient, $110 inpatient) for Stage 0-II patients and was $9,756 ($7,800 outpatient, $1,956 inpatient) for Stage III-IV patients. Conclusions: Treatment costs for melanoma are substantial in the first six months following diagnosis, especially for those patients with Stage III-IV disease.

No significant financial relationships to disclose.
Oblimersen in combination with dacarbazine prolongs prognostic factor-adjusted overall survival
Authors: Haluska F. G. , Bedikian A. Y. , Pavlick A. C. , Millward M. , Gore M. , Pehamberger H. , Trefzer U. , Eggermont A.
Published: April 2020

18006

Backgound: In a stratified randomized study comparing dacarbazine (DTIC) and oblimersen (Obl) with DTIC alone in metastatic melanoma, overall survival (OS) was increased in the Obl+DTIC group (P = .077). We report results from a multivariate analysis, including prognostic factors. Methods: The study enrolled 771 patients; 2.2% data were missing. Stratification factors included elevated LDH (>1.1 ULN), performance status (PS) >0, and metastatic site (MET): MET A = liver, MET B = other visceral, MET C = skin, subcutaneous, or lymph nodes only. Each stratification factor was evaluated using monovariate analysis for treatment interaction. Cox model included treatment, any identified factor, gender, or interaction term for OS and progression-free survival (PFS), and a logistic regression for response rate (RR). Results: The stratification factor with the greatest impact on survival was elevated LDH (HR 2.212, P < .0001), followed by PS > 0 (HR 1.497, P < .0001), MET A (HR 1.456, P < .0001), and MET C (HR 0.670, P < .0004). Interaction significance between treatment and LDH, PS, MET A, and MET C were 0.023, NS (0.279), NS (0.419), and NS (0.329), respectively. MET B was used as the reference category for MET A and MET C. Conclusion: As expected, all stratification factors were prognostic, with LDH being the most important factor (HR 2.2). The addition of Obl to DTIC treatment improved outcomes for all efficacy end points. A statistical interaction between Obl treatment and LDH was found for survival. Multivariate analysis was significant in all efficacy end points. Patients with abnormal baseline LDH, already understood to have a poor prognosis, were unlikely to benefit from this therapy and should not be included in future trials of combination oblimersen treatments.

[Table: see text]

No significant financial relationships to disclose.
YKL-40 expression in naevocellular naevi, carcinomas and melanomas of the skin
Authors: Schmidt H. , Roslind A. , Johansen J. S. , Nielsen D. L. , Price P. A. , Balslev E.
Published: April 2020

18019

Background: Elevated serum levels of the protein YKL-40 are associated with a poor prognosis in several solid tumors including melanoma (H. Schmidt, JCO 2006, Cancer 2006 in press). YKL-40 is secreted by cancer cells, macrophages and neutrophils. The function of YKL-40 is only poorly understood. It may be a growth or differentiation factor, play a role in angiogenesis or protect against apoptosis. The aim was to describe the tissue expression of YKL-40 in naevocellular naevi, carcinomas and melanomas of the skin by immunohistochemistry. Methods: Paraffin-embedded tissue sections from 40 patients with different naevocellular naevi, carcinomas and melanomas of the skin were developed with EnVision+ System-HRP K4007 (DakoCytomation) using a monoclonal antibody against YKL-40. The intensity of YKL-40 staining was scored using a semi-quantitative method. Results: YKL-40 protein expression appeared as a cytoplasmic, granular staining with no staining of membranes, nuclei or extracellular matrix. In normal skin the basal epithelial layer stained weakly positive. Melanocytes and melanophages stained negative. Macrophages and leucocytes stained positive. Hair follicles, sebaceous glands and sweat glands stained positive. Three basal cell carcinomas all stained positive. In 10 squamous cell carcinomas, the epidermal components stained positive and the invasive tumor islands were negative. In 3 keratoacanthomas, the epithelial components as well as the infiltrative tumor islands stained positive. In naevi (2 junctional, 5 compound and 1 intradermal) the epithelial components stained positive, the intradermal components stained negative. In melanomas the tumor cells stained positive in 9 of 10 specimens. Both the epidermal and the invasive components of melanomas stained positive. Three melanoma metastases all stained positive. Conclusions: YKL-40 is expressed in normal skin and in benign and malignant lesions of the skin. Generally, YKL-40 expression is increased in cells of high activity, although the invasive tumor islands of squamous cell carcinomas stain negative. In melanomas, the tumor cells may be a source of the elevated YKL-40 serum levels observed in these patients.

No significant financial relationships to disclose.
Elderly patients with advanced non-small cell lung cancer (nsclc). Results of chemotherapy and comparison with younger patients
Authors: Rubio I. , Martínez-Bueno A. , López-Vivanco G. , Fuente N. , Barceló R. , Gil-Negrete A. , Carrera S. , López-Argumedo G. , Fernández R. , Muñoz A.
Published: April 2020

18505

Background: Lung cancer is increasingly diagnosed in elderly patients and is the first cause of cancer death. Treatment of this subset represents a challenge to medical oncologists. Methods: We retrospectively reviewed clinical characteristics, co-morbidity (Charlson Index), toxicity and results of all patients ≥ 65 years (y) old, diagnosed of advanced NSCLC. We compared these results with younger patients’. Results: From January-95 to June-02, we treated 477 patients (pt), 176 ≥ 65 years, 301 < 65 y. Treatment: 177 pt, MIC (mitomycine + ifosfamide + cisplatin), 60 ≥ 65 y and 117 < 65 y; 156, CG (Cisplatin + Gemcitabine), 52 > 65 y and 104 < 65 y; 144, CP (Cisplatin + Paclitaxel), 64 ≥ 65 y and 120 < 65 y. Characteristics: median age 60 (31–78); 428 male, 49 female; ECOG 0/1/2/3: 83/312/71/5, Stage IIIA, IIIB and IV: 72/199/206, Histology: squamous carcinoma 215, adenocarcinoma 190, large cell 19, bronchioloalveolar 7, undifferentiated 45 pt. No significant differences between the two groups. Overall response rate: 39% (CR, 32.9%, PR, 6.1%), Stable disease 26.4% and Progressive disease, 26.4%. Patients ≥ 65 y: CR 5.7%, PR 45.5%, SD 23.3% and PD 18.2%. Patients < 65 y: CR 6.3% PR 25.6%, SD 28.2% and PD 31.2%. Predictive factors for response: ECOG and stage. Response rate was superior in patients ≥ 65 y and in patients ≥ 70 y. Overall survival: 38.29 weeks (w): < 65 y, 38.57 w; 65–70 y, 37.71 w and ≥ 70 y, 37 w. Multivariate analysis: ECOG, stage and sex were prognostic factors; age, histology, Charlson index and schedule treatment were not significant. Grade 3/4 episodes of toxicity: ≥ 65 y, 184/17, and < 65 y, 232/8. Treatment delays: ≥ 65 y, 115 and < 65 y, 100. Hospitalization due to toxicity: >≥ 65 y, 34 and < 65 y, 23. Treatment was stopped in 13 pt >≥ 65 y and in 7 pt < 65 y. Conclusions: Age is not a predictive factor for response to chemotherapy, neither a prognostic factor for survival. Charlson index does not seem to be useful for these patients. Although toxicity is superior, cisplatin-based schedules are safe and active.

No significant financial relationships to disclose.
Regional cooling significantly reduces liposomal doxorubicin-induced palmar-plantar erythrodysesthesias (PPE) in patients with recurrent ovarian cancer
Authors: Sayer R. A. , Apte S. , Tedjarati S. S.
Published: April 2020

18507

Objective: To evaluate the effect of regional cooling on the incidence and severity of liposomal doxorubicin-induced PPE in patients with recurrent ovarian cancer. Methods: Following IRB-approval, a retrospective chart review identified all patients treated with liposomal doxorubicin for recurrent ovarian cancer from 7/00 through 7/05. It was then determined whether patients received a regional cooling protocol, which involved placing hands and feet in ice water during chemotherapy infusion. Information was collected including patient demographics, prior chemotherapy, and grade and severity of PPE. Results: 73 women were treated for recurrent ovarian cancer with liposomal doxorubicin over the 5-year period. The median age was 58 years (range 24 to 82). The number of cycles ranged from 2 to 27 (median of 5). Liposomal doxorubicin dosages were available for 69 patients. Of the 69 patients, 4 patients were treated at 30 mg/m2, 64 patients were treated at 40mg/m2, and 1 patient was treated at 50mg/m2. The number of prior chemotherapy regimens ranged from 1 to 6 (median of 2.4) and the total number of all prior cycles ranged from 6 to 57 (median of 10). 25 of 73 patients (34%) were treated using the regional cooling protocol, while 48 of 73 (66%) were not. All incidences of PPE occurred in patients treated at the 40mg/m2 dosing. The overall incidence of PPE in the regional cooling group was 24% compared to 54% in the non-regional cooling group (p = 0.0067). In the regional cooling group, 12% had grade 1 PPE, 8% had grade 2 PPE, 4% had grade 3, and none developed grade 4 PPE. Of the 48 patients without regional cooling, 19% had grade 1 PPE, 15% had grade 2 PPE, 15% had grade 3, and 2 of 4% had grade 4 PPE. Of the 25 patients receiving regional cooling, 1 patient (4%) required discontinuation of liposomal doxorubicin due to grade 3 PPE while 11 patients of the 48 patients who did not receive regional cooling (23%) required discontinuation due to PPE (p = 0.048). The incidence of PPE was not associated with age at diagnosis or total number of previous chemotherapy cycles. Conclusions: Regional cooling is effective in significantly reducing the incidence and severity of liposomal doxorubicin-induced PPE in patients with recurrent ovarian cancer.

No significant financial relationships to disclose.
Darbepoetin alfa administered at varying intervals compared with weekly epoetin alfa for treating chemotherapy-induced anemia: A pooled analysis of 20 clinical trials
Authors: Glaspy J. , Henry D. , Canon J. L. , Lam H. , Lillie T.
Published: April 2020

18508

Background: Cancer patients (pts) often develop chemotherapy-induced anemia (CIA), resulting in an increased risk for transfusions and fatigue. The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) can reduce transfusion requirements, raise hemoglobin (Hb) levels, and decrease fatigue in pts with CIA. The 74-hour half-life of DA allows for flexible dosing with weekly (QW), every-2-week (Q2W), or every-3-week (Q3W) administration. This study evaluated if the dosing interval used to administer DA affected its efficacy. Methods: Data from 20 clinical trials in the CIA setting were pooled, including single-arm, active-controlled, and placebo-controlled trials (a full description of these studies will be presented). Six studies contributed data for DA QW, 7 studies for DA Q2W, and 5 studies for DA Q3W. Controlled studies used either a placebo or EA as the comparator. Logistic regression with treatment as a random effect was used to analyze the clinical trials. Endpoints included the percentage of pts requiring transfusions (from week 1 to end of the treatment period [EOTP] and from week 5 to EOTP), reaching a target Hb of ≥ 11 g/dL, and achieving ≥ 3 point change in FACT-F score from baseline (BL). Percentages were adjusted for BL Hb levels (< 10 vs ≥ 10 g/dL), whether pts received platinum chemotherapy (no vs yes), and for dosage adjustments. Results: The type of ESA used (EA or DA) did not appear to affect the percentage of study pts who achieved clinically meaningful endpoints (see Table ). The results from these analyses also suggest that the dosing interval at which DA was administered did not affect its efficacy in study pts (see Table ). Conclusions: DA administered at dosing intervals of QW, Q2W, or Q3W has comparable efficacy to EA QW. This flexibility allows DA administration to be synchronized with common chemotherapy schedules, which may increase pt convenience by reducing the number of clinic visits.

[Table: see text]

[Table: see text]
Toxicity in elderly breast cancer patients treated by a taxane based chemotherapy as adjuvant or neoadjuvant therapy for primary breast cancer
Authors: Loibl S. , Von Minckwitz G. , Elling D. , Janni W. , Kaufmann M. , Vescia S. , Eggemann H. , Harbeck N. , Nekljudova V. , Kuemmel S.
Published: April 2020

18509

Background: Elderly patients (pts) are more likely to develop haematological toxicity with anthracycline based regimen. There are no sufficient data available on toxicities especially in elderly pts who are treated by taxane containing regimen. Methods: Four prospective randomised trials in the treatment of primary breast cancer have been combined retrospectively to evaluate the toxicity in pts ≥ 60 treated by a taxane. Pts received either 1: docetaxel/adriamycin/cyclophosphamide (TAC 75/50/600 mg/m2), 2: adriamycin(epirubicin)/cyclophosphamide (A(E)/C: 60(90)/600 mgm2) followed by docetaxel (T: 100 mg/m2) or paclitaxel (P: 175mg/m2), or 3: dose-dense adriamycin/docetaxel (AT dd: 50/75 mg/m2) or 4: epirubicin-paclitaxel in sequence (E-P dd: 90–175 mg/m2). A descriptive analysis was performed in regards to pts and per cycles. In the sequential regimen cycles without taxanes were not considered evaluable. Results: 917 pts median age of 64 (range 60–80) years were included in this pooled analysis. 59 were older than 70 years. In total 3852 cycles of a taxane containing chemotherapy were administered. 378 pts (41.2%) received therapy 1, 332 (36.2%) therapy 2, 121 (13.2%) therapy 3, and 86 (9.4%) therapy 4. A total of 16 % of the pts did not complete treatment. Grade 3–4 neutropenia occurred in 46.2% and febrile neutropenia in 6.1% of the pts, severe anemia (0.8%) and thrombopenia (1.1%) was infrequent. Main non hematological toxicities were (% pts with grade I-IV): fatigue 86; loss of appetite 74; nausea and vomiting 68; mucositis 60; sensory neuropathy; conjunctivitis 45; skin 38; nail 39; fluid retention 36; dyspnea 32. Conclusion: Toxicity of taxanes in pts older than 60 years does not significantly differ from younger pts. Therefore, taxanes as adjuvant or neoadjuvant treatment for primary breast cancer could also be considered in otherwise fit pts in the age group of 60–70.

[Table: see text]
The effectiveness of darbepoetin alfa administered at 300 mcg every 3 weeks on clinical outcomes in elderly patients with chemotherapy-induced anemia
Authors: Boccia R. V. , Silberstein P. , Tchekmedyian S. , Tomita D. , Lillie T. , Otterson G.
Published: April 2020

18511

Background: Chemotherapy-induced anemia (CIA) is common in patients (pts) receiving chemotherapy, and reduces health-related quality of life. The primary objective of this exploratory analysis was to describe the effectiveness of darbepoetin alfa administered at 300 mcg every 3 weeks (Q3W) in elderly (≥ 65 years old) and younger pts (< 65 years old) with CIA. Methods: We analyzed data on 1493 pts, enrolled in a multicenter, open-label, 16-week study and who received ≥ 1 dose of darbepoetin alfa. Eligible pts were ≥ 18 years old, had a non-myeloid malignancy, and were anemic (hemoglobin [Hb] < 11 g/dL). Pts were analyzed stratified by age (≥ 65 and < 65 years old) and baseline (BL) Hb (< 10 or ≥ 10 g/dL). Hb-based endpoints were analyzed using 2 approaches: the last value carried forward (LVCF) method, where missing Hb values or values within 28 days of a red blood cell (RBC) transfusion were imputed, or an available data approach, where missing Hb values were not imputed. Pt-reported outcomes were assessed using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) scale. Results: Pt demographics and disease characteristics varied between the age strata: in the ≥ 65-stratum (mean age = 73.7, n = 724), 52% of pts were women and the most common cancer was gastrointestinal (27%); in the < 65-stratum (mean age = 52.1, n = 769), 69% of pts were women and the most common cancer was breast (41%). Mean (SD) BL FACT-F scores for pts ≥ 65 and < 65 were 27.5 (12.8) vs 27.2 (12.1) for the < 10-g/dL strata and 29.0 (12.5) vs 27.5 (12.0) for the ≥ 10-g/dL strata. Study endpoints are shown in the table. The safety profile was as expected for each age group. Conclusions: Darbepoetin alfa 300 mcg Q3W appears to be as effective in achieving and maintaining Hb between 11 to 13 g/dL in elderly pts as in younger pts with CIA. Since chemotherapy is often administered Q3W, synchronizing darbepoetin alfa treatment with pts’ chemotherapy schedules may simplify the treatment of CIA in this pt population.

[Table: see text]

[Table: see text]