http://ift.tt/2FhHigQ
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 5 Μαρτίου 2018
Psychometric Testing of the Fear of Cancer Recurrence Inventory- Caregiver Chinese Version in Cancer Family Caregivers in Taiwan
Abstract
Objective
The purposes of this study were to develop a Chinese version of the Fear of Cancer Recurrence Inventory-caregiver (FCRI-c Chinese) and assess the psychometrics of this test in the family caregivers (FCs) of Taiwanese patients with head and neck cancer (HNC).
Methods
An instrument testing study was conducted at a major medical center in Taiwan. HNC patients and their major FCs were recruited as dyads from the radiation outpatient department. The FCRI-c Chinese was tested for internal consistency reliability, test-retest reliability, and construct validity (including theoretically supported correlation, discriminant validity, and factor structure).
Results
We recruited 300 patient-caregiver dyads. The test had good internal consistency (Cronbach's alpha = 0.94) and a 2-week test-retest reliability of 0.88. Confirmatory factor analysis (CFA) indicated an acceptable fit of the model to the data. The construct validity was also satisfactory, as indicated by the significant positive correlations of the test with depression and anxiety in FCs, and the significant negative correlation of the test with patients' quality of life. A significantly higher test score was present in FCs caring for patients with metastasis and patients who completed treatment a longer time ago.
Conclusions
The FCRI-c Chinese is a valid instrument for examination of the FCR in the FCs of patients with HNC. Clinicians can use this multi-dimensional instrument to assess important clinical care issues and improve the quality of care provided by FCs.
http://ift.tt/2oX8FWH
Beyond using composite measures to analyze the effect of unmet supportive care needs on caregivers' anxiety and depression
Abstract
Objective
Caregiver research has relied on composite measures (e.g., count) of unmet supportive care needs to determine relationships with anxiety and depression. Such composite measures assume that all unmet needs have a similar impact on outcomes. The purpose of this study is to identify individual unmet needs most associated with caregivers' anxiety and depression.
Methods
219 Caregivers completed the 44-item Supportive Care Needs Survey and the Hospital Anxiety and Depression scale [minimal clinically important difference (MCID)=1.5] at 6-8 months, 1, 2, 3.5, and 5 years following the patients' cancer diagnosis. The list of needs was reduced using Partial Least Square regression and those with a Variance Importance in Projection > 1 were analyzed using Bayesian Model Averaging.
Results
Across time, eight items remained in the top 10 based on prevalence and were labelled "core". Three additional ones were labelled "frequent", as they remained in the top 10 from 1-year onwards. Bayesian Model Averaging identified a maximum of four significant unmet needs per time point – all leading to a difference greater than the MCID. For depression, none of the core unmet needs were significant, rather significance was noted for frequent needs and needs that were not prevalent. For anxiety, 3/8 core and 3/3 frequent unmet needs were significant.
Conclusions
Prevalent Those unmet needs that are most prevalent are not necessarily the most significant ones, and findings provide an evidence-based framework to guide the development of caregiver interventions. A broader contribution is proposing a different approach to identify significant unmet needs.
http://ift.tt/2I5a0Dt
Psychometric Testing of the Fear of Cancer Recurrence Inventory- Caregiver Chinese Version in Cancer Family Caregivers in Taiwan
Abstract
Objective
The purposes of this study were to develop a Chinese version of the Fear of Cancer Recurrence Inventory-caregiver (FCRI-c Chinese) and assess the psychometrics of this test in the family caregivers (FCs) of Taiwanese patients with head and neck cancer (HNC).
Methods
An instrument testing study was conducted at a major medical center in Taiwan. HNC patients and their major FCs were recruited as dyads from the radiation outpatient department. The FCRI-c Chinese was tested for internal consistency reliability, test-retest reliability, and construct validity (including theoretically supported correlation, discriminant validity, and factor structure).
Results
We recruited 300 patient-caregiver dyads. The test had good internal consistency (Cronbach's alpha = 0.94) and a 2-week test-retest reliability of 0.88. Confirmatory factor analysis (CFA) indicated an acceptable fit of the model to the data. The construct validity was also satisfactory, as indicated by the significant positive correlations of the test with depression and anxiety in FCs, and the significant negative correlation of the test with patients' quality of life. A significantly higher test score was present in FCs caring for patients with metastasis and patients who completed treatment a longer time ago.
Conclusions
The FCRI-c Chinese is a valid instrument for examination of the FCR in the FCs of patients with HNC. Clinicians can use this multi-dimensional instrument to assess important clinical care issues and improve the quality of care provided by FCs.
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Beyond using composite measures to analyze the effect of unmet supportive care needs on caregivers' anxiety and depression
Abstract
Objective
Caregiver research has relied on composite measures (e.g., count) of unmet supportive care needs to determine relationships with anxiety and depression. Such composite measures assume that all unmet needs have a similar impact on outcomes. The purpose of this study is to identify individual unmet needs most associated with caregivers' anxiety and depression.
Methods
219 Caregivers completed the 44-item Supportive Care Needs Survey and the Hospital Anxiety and Depression scale [minimal clinically important difference (MCID)=1.5] at 6-8 months, 1, 2, 3.5, and 5 years following the patients' cancer diagnosis. The list of needs was reduced using Partial Least Square regression and those with a Variance Importance in Projection > 1 were analyzed using Bayesian Model Averaging.
Results
Across time, eight items remained in the top 10 based on prevalence and were labelled "core". Three additional ones were labelled "frequent", as they remained in the top 10 from 1-year onwards. Bayesian Model Averaging identified a maximum of four significant unmet needs per time point – all leading to a difference greater than the MCID. For depression, none of the core unmet needs were significant, rather significance was noted for frequent needs and needs that were not prevalent. For anxiety, 3/8 core and 3/3 frequent unmet needs were significant.
Conclusions
Prevalent Those unmet needs that are most prevalent are not necessarily the most significant ones, and findings provide an evidence-based framework to guide the development of caregiver interventions. A broader contribution is proposing a different approach to identify significant unmet needs.
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Stigma and its influencing factors among Chinese patients with stoma
Abstract
Background
Although stomas are necessary for disease treatment, they unavoidably affect patients' lives from physical, psychological, social, spiritual and familial perspectives and contribute to feelings of embarrassment and shame. This study explored the current status and factors influencing stigma among Chinese patients with stoma.
Methods
A total of 209 patients with stoma at the stoma clinic of a tertiary cancer centre in Guangzhou, China, were recruited and investigated using the Social Impact Scale, the Coping Self-Efficacy Scale, the State Self-Esteem Scale, and a demographic questionnaire. Multivariate linear regression was used to identify the factors influencing stigma.
Results
The mean Social Impact Scale score was 69.65±13.18, which represents a moderate effect; specifically, 44% of the patients experienced high levels of stigma. Stoma patients with the following characteristics had high levels of stigma: young, low coping self-efficacy, low stoma acceptance by one's spouse or other family members, poor perceived body image, stool leakage, no experience of participating in activities with other stoma patients.
Conclusions
Medical staff members should pay more attention to stigma in stoma patients. Coping self-efficacy, family members' acceptance of the stoma and participation in activities with other stoma patients are influencing factors that protect these patients against stigma, whereas body image loss and stool leakage place them at higher risk for stigma. Interventions aimed at improving protective factors and decreasing risk factors should be considered to reduce the level of stigma in patients with stoma.
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Cover Image
The cover image, by Selene Xu et al., is based on the Paper Cognition, quality-of-life and symptom clusters in breast cancer: Using Bayesian networks to elucidate complex relationships, DOI 10.1002/pon.4571.
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Stigma and its influencing factors among Chinese patients with stoma
Abstract
Background
Although stomas are necessary for disease treatment, they unavoidably affect patients' lives from physical, psychological, social, spiritual and familial perspectives and contribute to feelings of embarrassment and shame. This study explored the current status and factors influencing stigma among Chinese patients with stoma.
Methods
A total of 209 patients with stoma at the stoma clinic of a tertiary cancer centre in Guangzhou, China, were recruited and investigated using the Social Impact Scale, the Coping Self-Efficacy Scale, the State Self-Esteem Scale, and a demographic questionnaire. Multivariate linear regression was used to identify the factors influencing stigma.
Results
The mean Social Impact Scale score was 69.65±13.18, which represents a moderate effect; specifically, 44% of the patients experienced high levels of stigma. Stoma patients with the following characteristics had high levels of stigma: young, low coping self-efficacy, low stoma acceptance by one's spouse or other family members, poor perceived body image, stool leakage, no experience of participating in activities with other stoma patients.
Conclusions
Medical staff members should pay more attention to stigma in stoma patients. Coping self-efficacy, family members' acceptance of the stoma and participation in activities with other stoma patients are influencing factors that protect these patients against stigma, whereas body image loss and stool leakage place them at higher risk for stigma. Interventions aimed at improving protective factors and decreasing risk factors should be considered to reduce the level of stigma in patients with stoma.
http://ift.tt/2H7BmaB
Cover Image
The cover image, by Selene Xu et al., is based on the Paper Cognition, quality-of-life and symptom clusters in breast cancer: Using Bayesian networks to elucidate complex relationships, DOI 10.1002/pon.4571.
http://ift.tt/2H7BerD
Pituitary height at magnetic resonance imaging in pediatric isolated growth hormone deficiency
Abstract
Background
Magnetic resonance imaging (MRI) is used for neuroradiologic evaluation of patients with idiopathic growth hormone deficiency (IGHD).
Objectives
To compare pituitary height and morphology at MRI between patients with IGHD and controls.
Materials and methods
This retrospective study was conducted in pediatric patients, 3 years–15 years old, who had had brain MRI with non-contrast-enhanced midsagittal T1-weighted images. These images were measured for pituitary height and morphology of the pituitary gland including shape, stalk and posterior pituitary bright spot was evaluated.
Results
One hundred and nineteen patients were included, with 49 and 70 patients assigned to the study and control groups, respectively. Mean pituitary height was significantly less in the IGHD group than in the control group (3.81 mm±1.38 vs. 4.92 mm±1.13, retrospectively; P<0.001). Subgroup analysis revealed a significant difference in the pituitary height between groups in the prepubertal (8–10 years) and pubertal (11–13 years) periods (P=0.039 and P=0.006, respectively) and a trend toward significance in the postpubertal period (P=0.053). There was a significant difference in pituitary shape between IGHD and controls when combining grades III, IV and V (P=0.007). Other abnormal MRI findings of the pituitary stalk and posterior bright spot were significantly more often observed in the IGHD group (P<0.05).
Conclusion
Pituitary height was significantly smaller in patients with IGHD than in controls during prepuberty and puberty. Abnormal concave superior contour, hypoplastic stalk and absent/ectopic posterior bright spot were observed significantly more often among patients with IGHD.
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Long-term Outcomes After Stereotactic Radiosurgery for Spine Metastases: Radiation Dose-Response for Late Toxicity
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Diane C. Ling, John C. Flickinger, Steven A. Burton, Dwight E. Heron, Annette E. Quinn, Ghassan K. Bejjani, Johnathan A. Engh, Peter C. Gerszten, Nduka M. Amankulor, John A. Vargo
BackgroundWhile a large body of data supports the safety and efficacy of stereotactic radiosurgery (SRS) for the primary treatment and re-irradiation of spine metastases, concerns over late toxicity inherent to hypofractionation remain, as follow-up in most series is limited to 1-2 years.MethodsA retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction SRS to a median dose of 16Gy (range: 12-24), and 56% of sites had received prior external beam radiation therapy. Late toxicities and vertebral compression fractures (VCF) occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications.ResultsNine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8 months (range: 4.2-59.0). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative BED3 >200Gy (or EQD22Gy >130Gy) was associated with grade ≥2 late toxicity (p=0.036). Maximum point BED3 >110Gy (or EQD22Gy >70Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy (p=0.017). Nine (18%) VCFs occurred at a median time of 10.2 months (range: 3.2-57.2), with 5- and 10-year VCF rates of 17% and 17%, respectively.ConclusionSRS for primary treatment and re-irradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED3 >200Gy and spinal cord or cauda equina point BED3 >110Gy. Patients remain at moderate risk of VCF up to 5-years following treatment, with a plateau in incidence thereafter up to 10 years.
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Pituitary height at magnetic resonance imaging in pediatric isolated growth hormone deficiency
Abstract
Background
Magnetic resonance imaging (MRI) is used for neuroradiologic evaluation of patients with idiopathic growth hormone deficiency (IGHD).
Objectives
To compare pituitary height and morphology at MRI between patients with IGHD and controls.
Materials and methods
This retrospective study was conducted in pediatric patients, 3 years–15 years old, who had had brain MRI with non-contrast-enhanced midsagittal T1-weighted images. These images were measured for pituitary height and morphology of the pituitary gland including shape, stalk and posterior pituitary bright spot was evaluated.
Results
One hundred and nineteen patients were included, with 49 and 70 patients assigned to the study and control groups, respectively. Mean pituitary height was significantly less in the IGHD group than in the control group (3.81 mm±1.38 vs. 4.92 mm±1.13, retrospectively; P<0.001). Subgroup analysis revealed a significant difference in the pituitary height between groups in the prepubertal (8–10 years) and pubertal (11–13 years) periods (P=0.039 and P=0.006, respectively) and a trend toward significance in the postpubertal period (P=0.053). There was a significant difference in pituitary shape between IGHD and controls when combining grades III, IV and V (P=0.007). Other abnormal MRI findings of the pituitary stalk and posterior bright spot were significantly more often observed in the IGHD group (P<0.05).
Conclusion
Pituitary height was significantly smaller in patients with IGHD than in controls during prepuberty and puberty. Abnormal concave superior contour, hypoplastic stalk and absent/ectopic posterior bright spot were observed significantly more often among patients with IGHD.
http://ift.tt/2FWMwzM
Long-term Outcomes After Stereotactic Radiosurgery for Spine Metastases: Radiation Dose-Response for Late Toxicity
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Diane C. Ling, John C. Flickinger, Steven A. Burton, Dwight E. Heron, Annette E. Quinn, Ghassan K. Bejjani, Johnathan A. Engh, Peter C. Gerszten, Nduka M. Amankulor, John A. Vargo
BackgroundWhile a large body of data supports the safety and efficacy of stereotactic radiosurgery (SRS) for the primary treatment and re-irradiation of spine metastases, concerns over late toxicity inherent to hypofractionation remain, as follow-up in most series is limited to 1-2 years.MethodsA retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction SRS to a median dose of 16Gy (range: 12-24), and 56% of sites had received prior external beam radiation therapy. Late toxicities and vertebral compression fractures (VCF) occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications.ResultsNine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8 months (range: 4.2-59.0). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative BED3 >200Gy (or EQD22Gy >130Gy) was associated with grade ≥2 late toxicity (p=0.036). Maximum point BED3 >110Gy (or EQD22Gy >70Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy (p=0.017). Nine (18%) VCFs occurred at a median time of 10.2 months (range: 3.2-57.2), with 5- and 10-year VCF rates of 17% and 17%, respectively.ConclusionSRS for primary treatment and re-irradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED3 >200Gy and spinal cord or cauda equina point BED3 >110Gy. Patients remain at moderate risk of VCF up to 5-years following treatment, with a plateau in incidence thereafter up to 10 years.
http://ift.tt/2FlCSW0
A phase II trial to evaluate the efficacy of panitumumab combined with fluorouracil-based chemotherapy for metastatic colorectal cancer: the PF trial
Abstract
Purpose
Fluorouracil monotherapy, instead of the FOLFOX or FOLFIRI regimen, is administered to patients intolerant to oxaliplatin or irinotecan because of their adverse effects. A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan. Screening for potential serum biomarkers to predict early therapeutic responses was conducted.
Methods
This single-arm, open-label multicenter phase II trial recruited patients with KRAS WT mCRC from 16 institutes between January 2012 and October 2014. Panitumumab (6 mg/kg) was intravenously administered every 2 weeks, combined with fluorouracil monotherapy, in 2-week cycles. The primary objective was overall response rate, and secondary endpoints included disease-control rate, progression-free survival, overall survival, toxicity, and blood-test data.
Results
Forty patients (male, 65.0%; median age, 74 years; colon cancer, 72.5%) met eligibility criteria and received 7 cycles (median) of fluorouracil chemotherapy combined with panitumumab. There were no treatment-related deaths. Median time to treatment failure was 3.2 months. 23 (57.5%) patients experienced at least one adverse effect ≥ grade 3. The response rate was 10.0% (95% confidence interval 2.8–23.7%). Median progression-free survival and overall survival were 4.3 and 11.3 months, respectively. Total lactase dehydrogenase (LDH) levels and those of LDH-4 and LDH-5, quickly changed with disease reduction or progression.
Conclusions
Fluorouracil monotherapy combined with panitumumab was safely administered to patients with KRAS WT mCRC intolerant to oxaliplatin and irinotecan. Serum LDH levels may predict early responses.
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A phase II trial to evaluate the efficacy of panitumumab combined with fluorouracil-based chemotherapy for metastatic colorectal cancer: the PF trial
Abstract
Purpose
Fluorouracil monotherapy, instead of the FOLFOX or FOLFIRI regimen, is administered to patients intolerant to oxaliplatin or irinotecan because of their adverse effects. A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan. Screening for potential serum biomarkers to predict early therapeutic responses was conducted.
Methods
This single-arm, open-label multicenter phase II trial recruited patients with KRAS WT mCRC from 16 institutes between January 2012 and October 2014. Panitumumab (6 mg/kg) was intravenously administered every 2 weeks, combined with fluorouracil monotherapy, in 2-week cycles. The primary objective was overall response rate, and secondary endpoints included disease-control rate, progression-free survival, overall survival, toxicity, and blood-test data.
Results
Forty patients (male, 65.0%; median age, 74 years; colon cancer, 72.5%) met eligibility criteria and received 7 cycles (median) of fluorouracil chemotherapy combined with panitumumab. There were no treatment-related deaths. Median time to treatment failure was 3.2 months. 23 (57.5%) patients experienced at least one adverse effect ≥ grade 3. The response rate was 10.0% (95% confidence interval 2.8–23.7%). Median progression-free survival and overall survival were 4.3 and 11.3 months, respectively. Total lactase dehydrogenase (LDH) levels and those of LDH-4 and LDH-5, quickly changed with disease reduction or progression.
Conclusions
Fluorouracil monotherapy combined with panitumumab was safely administered to patients with KRAS WT mCRC intolerant to oxaliplatin and irinotecan. Serum LDH levels may predict early responses.
http://ift.tt/2Fh6uEc
4π plan optimization for cortical-sparing brain radiotherapy
Incidental irradiation of normal brain tissue during radiotherapy is linked to cognitive decline, and may be mediated by damage to healthy cortex. Non-coplanar techniques may be used for cortical sparing. We compared normal brain sparing and probability of cortical atrophy using 4π radiation therapy planning vs. standard fixed gantry intensity-modulated radiotherapy (IMRT).
http://ift.tt/2FgBNis
Antitumor and radiosensitizing effects of SKLB-163, a novel benzothiazole-2-thiol derivative, on nasopharyngeal carcinoma by affecting the RhoGDI/JNK-1 signaling pathway
SKLB-163 is a novel benzothiazole-2-thiol derivative with antitumor activities. This study investigated the effects of SKLB-163 on nasopharyngeal carcinoma (NPC) and its mechanisms.
http://ift.tt/2FdX5RD
More than a Conversation: the Power of Bringing Scientists and the Community Together to Change Perceptions About Cancer
Abstract
According to the Centers for Disease Control and Prevention, up to 40% of annual deaths are due to preventable, modifiable risk factors (Centers for Disease Control and Prevention 2014). Evidence in the literature suggests that increased knowledge and engagement is a critical step in preventing disease and improving health behaviors (Health Promotion International 15(3):259–267, 2000; Risk Manag Healthc Policy 3:61-72, 2010; Urology 61(2):308-313, 2003). Educational seminars, titled Conversations with Scientists, are offered twice per year by the Advancing a Healthier Wisconsin Endowment with the goal of helping community members, patients, and families inform themselves and others about science and health. In the first series, Cancer: Past, Present, and Future, the goals of increasing (1) knowledge, (2) intent to improve health behaviors, and (3) intent to disseminate information to friends and family were evaluated. Additionally, focus groups and interviews were conducted with speakers and audience members to explore strengths of the existing program format and opportunities to improve. The World Health Organization estimates that between 30 and 50% of all cancer cases are preventable, and has called for efforts to raise public awareness of cancer risks (World Health Organization 2017). Findings indicate that the existing seminar format achieved its intended goals, and provided additional value that can be leveraged to improve health outcomes for participants and their families.
http://ift.tt/2FY5iXC
More than a Conversation: the Power of Bringing Scientists and the Community Together to Change Perceptions About Cancer
Abstract
According to the Centers for Disease Control and Prevention, up to 40% of annual deaths are due to preventable, modifiable risk factors (Centers for Disease Control and Prevention 2014). Evidence in the literature suggests that increased knowledge and engagement is a critical step in preventing disease and improving health behaviors (Health Promotion International 15(3):259–267, 2000; Risk Manag Healthc Policy 3:61-72, 2010; Urology 61(2):308-313, 2003). Educational seminars, titled Conversations with Scientists, are offered twice per year by the Advancing a Healthier Wisconsin Endowment with the goal of helping community members, patients, and families inform themselves and others about science and health. In the first series, Cancer: Past, Present, and Future, the goals of increasing (1) knowledge, (2) intent to improve health behaviors, and (3) intent to disseminate information to friends and family were evaluated. Additionally, focus groups and interviews were conducted with speakers and audience members to explore strengths of the existing program format and opportunities to improve. The World Health Organization estimates that between 30 and 50% of all cancer cases are preventable, and has called for efforts to raise public awareness of cancer risks (World Health Organization 2017). Findings indicate that the existing seminar format achieved its intended goals, and provided additional value that can be leveraged to improve health outcomes for participants and their families.
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Clinical and economic burden associated with stage III to IV triple-negative breast cancer: A SEER-Medicare historical cohort study in elderly women in the United States
BACKGROUND
The current study was performed to describe patient characteristics, treatment patterns, survival, health care resource use (HRU), and costs among older women in the United States with advanced (American Joint Committee on Cancer stage III/IV) triple-negative breast cancer (TNBC) in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.
METHODS
Women who were aged ≥66 years at the time of diagnosis and diagnosed with advanced TNBC between January 1, 2007, and January 1, 2011, in the SEER-Medicare database and who were followed for survival through December 31, 2013, were eligible. Patient demographic and clinical characteristics at the time of diagnosis, subsequent treatment patterns, and survival outcomes were analyzed. HRU and costs for the first 3 months after diagnosis, the last 3 months of life, and the time in between are summarized. All analyses were stratified by American Joint Committee on Cancer stage of disease.
RESULTS
There were 1244 patients newly diagnosed with advanced TNBC; the majority were aged ≥75 years (61% with stage III disease and 57.4% with stage IV disease) and white (>70% of patients in both disease stage groups). The most common treatment approaches were surgery combined with chemotherapy for patients for stage III disease (50.6%) and chemotherapy alone or with radiotherapy for patients with stage IV disease (31.3%). Diverse chemotherapy regimens were administered for each line of therapy; nevertheless, the medications used were consistent with national guidelines. Patients with stage III and stage IV disease were found to have a similar mean number of hospitalizations and outpatient visits, but mean monthly costs were greater for patients with stage IV disease at all 3 time points. The mean cost per patient-month (in 2013 US dollars) was $4810 for patients with stage III disease and $9159 for patients with stage IV disease.
CONCLUSIONS
Among older women with advanced TNBC, significant treatment variations and considerable HRU and costs exist. Further research is needed to find effective treatments with which to reduce the clinical and economic burden of this disease. Cancer 2018. © 2018 American Cancer Society.
http://ift.tt/2I4X68D
Clinical and economic burden associated with stage III to IV triple-negative breast cancer: A SEER-Medicare historical cohort study in elderly women in the United States
BACKGROUND
The current study was performed to describe patient characteristics, treatment patterns, survival, health care resource use (HRU), and costs among older women in the United States with advanced (American Joint Committee on Cancer stage III/IV) triple-negative breast cancer (TNBC) in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.
METHODS
Women who were aged ≥66 years at the time of diagnosis and diagnosed with advanced TNBC between January 1, 2007, and January 1, 2011, in the SEER-Medicare database and who were followed for survival through December 31, 2013, were eligible. Patient demographic and clinical characteristics at the time of diagnosis, subsequent treatment patterns, and survival outcomes were analyzed. HRU and costs for the first 3 months after diagnosis, the last 3 months of life, and the time in between are summarized. All analyses were stratified by American Joint Committee on Cancer stage of disease.
RESULTS
There were 1244 patients newly diagnosed with advanced TNBC; the majority were aged ≥75 years (61% with stage III disease and 57.4% with stage IV disease) and white (>70% of patients in both disease stage groups). The most common treatment approaches were surgery combined with chemotherapy for patients for stage III disease (50.6%) and chemotherapy alone or with radiotherapy for patients with stage IV disease (31.3%). Diverse chemotherapy regimens were administered for each line of therapy; nevertheless, the medications used were consistent with national guidelines. Patients with stage III and stage IV disease were found to have a similar mean number of hospitalizations and outpatient visits, but mean monthly costs were greater for patients with stage IV disease at all 3 time points. The mean cost per patient-month (in 2013 US dollars) was $4810 for patients with stage III disease and $9159 for patients with stage IV disease.
CONCLUSIONS
Among older women with advanced TNBC, significant treatment variations and considerable HRU and costs exist. Further research is needed to find effective treatments with which to reduce the clinical and economic burden of this disease. Cancer 2018. © 2018 American Cancer Society.
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Development and Validation of a Prediction Model for Postoperative Peritoneal Metastasis After Curative Resection of Colon Cancer
Abstract
Background
Detection of peritoneal metastasis remains challenging due to the limited sensitivity of current examination methods. This study aimed to establish a prediction model for estimating the individual risk of postoperative peritoneal metastasis from colon cancer to facilitate early interventions for high-risk patients.
Methods
This study investigated 1720 patients with stages 1–3 colon cancer who underwent curative resection at the University of Tokyo Hospital between 1997 and 2015. The data for the patients were retrospectively retrieved from their medical records. The risk score was developed using the elastic net techniques in a derivation cohort (973 patients treated in 1997–2009) and validated in a validation cohort (747 patients treated in 2010–2015).
Results
The factors selected using the elastic net approaches included the T stage, N stage, number of examined lymph nodes, preoperative carcinoembryonic antigen level, large bowel obstruction, and anastomotic leakage. The model had good discrimination (c-index, 0.85) and was well-calibrated after application of the bootstrap resampling method. Discrimination and calibration were favorable in external validation (c-index, 0.83). The model presented a clear stratification of patients' risk for postoperative peritoneal recurrence, and decision curve analysis showed its net benefit across a wide range of threshold probabilities.
Conclusions
This study established and validated a prediction model that can aid clinicians in optimizing postoperative surveillance and therapeutic strategies according to the individual patient risk of peritoneal recurrence.
http://ift.tt/2tiSpVk
Development and Validation of a Prediction Model for Postoperative Peritoneal Metastasis After Curative Resection of Colon Cancer
Abstract
Background
Detection of peritoneal metastasis remains challenging due to the limited sensitivity of current examination methods. This study aimed to establish a prediction model for estimating the individual risk of postoperative peritoneal metastasis from colon cancer to facilitate early interventions for high-risk patients.
Methods
This study investigated 1720 patients with stages 1–3 colon cancer who underwent curative resection at the University of Tokyo Hospital between 1997 and 2015. The data for the patients were retrospectively retrieved from their medical records. The risk score was developed using the elastic net techniques in a derivation cohort (973 patients treated in 1997–2009) and validated in a validation cohort (747 patients treated in 2010–2015).
Results
The factors selected using the elastic net approaches included the T stage, N stage, number of examined lymph nodes, preoperative carcinoembryonic antigen level, large bowel obstruction, and anastomotic leakage. The model had good discrimination (c-index, 0.85) and was well-calibrated after application of the bootstrap resampling method. Discrimination and calibration were favorable in external validation (c-index, 0.83). The model presented a clear stratification of patients' risk for postoperative peritoneal recurrence, and decision curve analysis showed its net benefit across a wide range of threshold probabilities.
Conclusions
This study established and validated a prediction model that can aid clinicians in optimizing postoperative surveillance and therapeutic strategies according to the individual patient risk of peritoneal recurrence.
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Seven-month prostate-specific antigen (PSA) is prognostic in patients with prostate cancer initially diagnosed with distant metastases
Abstract
Recent research suggests that prostate-specific antigen (PSA) ≤ 0.2 ng/dl at 7 months is prognostic for better survival with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer regardless of chemotherapy with docetaxel. These results were derived from a group of clinical trial participants. Therefore, we performed a confirmatory analysis in patients treated outside of trials. Furthermore, we limited inclusion to those who presented with metastases at the initial diagnosis of prostate cancer (synchronous metastases). A retrospective analysis of a comprehensive regional database was performed. The oncology care in this region (Nordland County, Northern Norway) was provided by one center. Patients who were diagnosed between January 01, 2004 and December 31, 2016 were included. Of 101 patients, 90 were alive at 7 months and had their PSA value measured. Their median age was 68.5 years. Only six patients (7%) achieved PSA ≤ 0.2 ng/dl at 7 months. The median value was 4.05 ng/dl. Median overall survival was shortest in patients with PSA > 4.0 ng/dl (22 months). For patients with PSA between 0.3 and 4.0 ng/dl, median survival was 54 months (p = 0.0001). No further increase was seen in the small group with lower PSA. Statistical significance was also found for a cutoff of ≤ 1.0 ng/dl (55 vs. 32 months). PSA at 7 months predicts overall survival. Given that only 7% of patients achieved PSA ≤ 0.2 ng/dl, confirmation of this particular cutoff requires additional studies in other populations.
http://ift.tt/2FdMaYk
Seven-month prostate-specific antigen (PSA) is prognostic in patients with prostate cancer initially diagnosed with distant metastases
Abstract
Recent research suggests that prostate-specific antigen (PSA) ≤ 0.2 ng/dl at 7 months is prognostic for better survival with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer regardless of chemotherapy with docetaxel. These results were derived from a group of clinical trial participants. Therefore, we performed a confirmatory analysis in patients treated outside of trials. Furthermore, we limited inclusion to those who presented with metastases at the initial diagnosis of prostate cancer (synchronous metastases). A retrospective analysis of a comprehensive regional database was performed. The oncology care in this region (Nordland County, Northern Norway) was provided by one center. Patients who were diagnosed between January 01, 2004 and December 31, 2016 were included. Of 101 patients, 90 were alive at 7 months and had their PSA value measured. Their median age was 68.5 years. Only six patients (7%) achieved PSA ≤ 0.2 ng/dl at 7 months. The median value was 4.05 ng/dl. Median overall survival was shortest in patients with PSA > 4.0 ng/dl (22 months). For patients with PSA between 0.3 and 4.0 ng/dl, median survival was 54 months (p = 0.0001). No further increase was seen in the small group with lower PSA. Statistical significance was also found for a cutoff of ≤ 1.0 ng/dl (55 vs. 32 months). PSA at 7 months predicts overall survival. Given that only 7% of patients achieved PSA ≤ 0.2 ng/dl, confirmation of this particular cutoff requires additional studies in other populations.
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Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) vs. cetuximab in combination with FOLFIRI in RAS wild-type metastatic colorectal cancer
Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. Experimental design: mCRC patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. Results: Of 134 randomized patients, 98 were RAS ex2/3 wild-type. Duligotuzumab provided no PFS or OR benefit compared to cetuximab; though there was a trend for lower ORR in the duligotuzumab arm. No relationship was seen between PFS or ORR and ERBB3, NRG1, or AREG expression. There were fewer skin rash events for duligotuzumab but more diarrhea. Although the incidence of grade ≥ 3 AEs was similar, the frequency of serious AEs was higher for duligotuzumab. Conclusions: Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with RAS exon 2/3 wild-type mCRC compared to cetuximab + FOLFIRI.
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Investigating novel resistance mechanisms to third-generation EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancer patients
Background: The third generation EGFR tyrosine kinase inhibitor osimertinib is approved to treat EGFR T790M-positive non-small cell lung cancer (NSCLC) patients who have developed resistance to earlier generation drugs. Acquired EGFR C797S mutation has been reported to mediate osimertinib-resistance in some patients. However, the remaining resistance mechanisms are largely unknown. Methods: We performed mutation profiling using targeted next-generation sequencing (NGS) for 416 cancer-relevant genes on 93 osimertinib-resistant lung cancer patients' samples, mainly cell-free DNAs (cfDNA), and matched pre-treatment samples of 12 patients. In vitro experiments were conducted to functionally study the secondary EGFR mutations identified. Results: EGFR G796/C797, L792 and L718/G719 mutations were identified in 24.7%, 10.8% and 9.7% of the cases, respectively, with certain mutations co-existing in one patient with different prevalence. L792 and L718 mutants markedly increased the half inhibitory concentration (IC50) of osimertinib in vitro, among which the L718Q mutation conferred the greatest resistance to osimertinib, as well as gefitinib-resistance when not co-existing with T790M. Further analysis of the 12 matched pre-treatment samples confirmed that these EGFR mutations were acquired during osimertinib treatment. Alterations in parallel or downstream oncogenes such as MET, KRAS and PIK3CA were also discovered, potentially contributing to the osimertinib-resistance in patients without EGFR secondary mutations. Conclusions: We present comprehensive mutation profiles of a large cohort of osimertinib-resistance lung cancer patients using mainly cfDNA. Besides C797 mutations, novel secondary mutations of EGFR L718 and L792 residues confer osimertinib resistance, both in vitro and in vivo, and are of great clinical and pharmaceutical relevance.
http://ift.tt/2FpfjyT
Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) vs. cetuximab in combination with FOLFIRI in RAS wild-type metastatic colorectal cancer
Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. Experimental design: mCRC patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. Results: Of 134 randomized patients, 98 were RAS ex2/3 wild-type. Duligotuzumab provided no PFS or OR benefit compared to cetuximab; though there was a trend for lower ORR in the duligotuzumab arm. No relationship was seen between PFS or ORR and ERBB3, NRG1, or AREG expression. There were fewer skin rash events for duligotuzumab but more diarrhea. Although the incidence of grade ≥ 3 AEs was similar, the frequency of serious AEs was higher for duligotuzumab. Conclusions: Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with RAS exon 2/3 wild-type mCRC compared to cetuximab + FOLFIRI.
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Investigating novel resistance mechanisms to third-generation EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancer patients
Background: The third generation EGFR tyrosine kinase inhibitor osimertinib is approved to treat EGFR T790M-positive non-small cell lung cancer (NSCLC) patients who have developed resistance to earlier generation drugs. Acquired EGFR C797S mutation has been reported to mediate osimertinib-resistance in some patients. However, the remaining resistance mechanisms are largely unknown. Methods: We performed mutation profiling using targeted next-generation sequencing (NGS) for 416 cancer-relevant genes on 93 osimertinib-resistant lung cancer patients' samples, mainly cell-free DNAs (cfDNA), and matched pre-treatment samples of 12 patients. In vitro experiments were conducted to functionally study the secondary EGFR mutations identified. Results: EGFR G796/C797, L792 and L718/G719 mutations were identified in 24.7%, 10.8% and 9.7% of the cases, respectively, with certain mutations co-existing in one patient with different prevalence. L792 and L718 mutants markedly increased the half inhibitory concentration (IC50) of osimertinib in vitro, among which the L718Q mutation conferred the greatest resistance to osimertinib, as well as gefitinib-resistance when not co-existing with T790M. Further analysis of the 12 matched pre-treatment samples confirmed that these EGFR mutations were acquired during osimertinib treatment. Alterations in parallel or downstream oncogenes such as MET, KRAS and PIK3CA were also discovered, potentially contributing to the osimertinib-resistance in patients without EGFR secondary mutations. Conclusions: We present comprehensive mutation profiles of a large cohort of osimertinib-resistance lung cancer patients using mainly cfDNA. Besides C797 mutations, novel secondary mutations of EGFR L718 and L792 residues confer osimertinib resistance, both in vitro and in vivo, and are of great clinical and pharmaceutical relevance.
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Cancer Awareness and Behavioral Determinants Associated with Cancer Prevention—a Quantitative Study Among Young Adults in Rural Settings
Abstract
Although college is a crucial time to establish healthy behaviors for cancer prevention, little is known about cancer awareness and behaviors among US college students in less economically developed, rural areas. The purpose of this study was to examine college students' cancer-preventative knowledge and health behaviors. This cross-sectional study was conducted at a large southeastern university in the USA, on a convenience sample of students attending a campus-wide health education class. Data were collected during April and May 2017. Pearson's chi-square tests, independent samples t test, and one-way ANOVA were used. Participants (n = 1511) were female (59.1%), non-Hispanic White (69.7%), first-year college students (76.7%), and either 18 (35.9%) or 19 (44.6%) years old. Participants recognized an average of 6.69 (SD = 3.08) out of 11 risk factors on the Cancer Awareness Measure (Cronbach's alpha = 0.874), with a statistically significant difference observed by gender (t(1471) = − 3.348, p = 0.001), but not by race ((F(2,1474) = 1.742, p = 0.176). Chi-square analyses revealed significant associations by gender for exercise (p < 0.001), tobacco use (p < 0.001), and alcohol use (p < 0.001). Significant associations were also found by race/ethnicity for exercise (p < 0.001), tobacco use (p < 0.001), alcohol use (p < 0.001), and fruit and vegetable consumption (p = 0.035). Findings indicate a need to educate college students to recognize and modify cancer-related behavioral risk factors, particularly dietary habits. Specifically, health campaigns to reduce gender and racial gaps in cancer-preventative knowledge and behavior among first-year students are recommended.
http://ift.tt/2FfVZko
Cancer Awareness and Behavioral Determinants Associated with Cancer Prevention—a Quantitative Study Among Young Adults in Rural Settings
Abstract
Although college is a crucial time to establish healthy behaviors for cancer prevention, little is known about cancer awareness and behaviors among US college students in less economically developed, rural areas. The purpose of this study was to examine college students' cancer-preventative knowledge and health behaviors. This cross-sectional study was conducted at a large southeastern university in the USA, on a convenience sample of students attending a campus-wide health education class. Data were collected during April and May 2017. Pearson's chi-square tests, independent samples t test, and one-way ANOVA were used. Participants (n = 1511) were female (59.1%), non-Hispanic White (69.7%), first-year college students (76.7%), and either 18 (35.9%) or 19 (44.6%) years old. Participants recognized an average of 6.69 (SD = 3.08) out of 11 risk factors on the Cancer Awareness Measure (Cronbach's alpha = 0.874), with a statistically significant difference observed by gender (t(1471) = − 3.348, p = 0.001), but not by race ((F(2,1474) = 1.742, p = 0.176). Chi-square analyses revealed significant associations by gender for exercise (p < 0.001), tobacco use (p < 0.001), and alcohol use (p < 0.001). Significant associations were also found by race/ethnicity for exercise (p < 0.001), tobacco use (p < 0.001), alcohol use (p < 0.001), and fruit and vegetable consumption (p = 0.035). Findings indicate a need to educate college students to recognize and modify cancer-related behavioral risk factors, particularly dietary habits. Specifically, health campaigns to reduce gender and racial gaps in cancer-preventative knowledge and behavior among first-year students are recommended.
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I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma
Abstract
Background
I-124 codrituzumab (aka GC33), an antibody directed at Glypican 3, was evaluated in patients with hepatocellular carcinoma (HCC). Fourteen patients with HCC underwent baseline imaging with I-124 codrituzumab (~ 185 MBq, 10 mg). Seven of these patients undergoing sorafenib/immunotherapy with 2.5 or 5 mg/kg of cold codrituzumab had repeat imaging, with co-infusion of I-124 codrituzumab, as part of their immunotherapy treatment. Three patients who progressed while on sorafenib/immunotherapy were re-imaged after a 4-week washout period to assess for the presence of antigen. Serial positron emission tomography (PET) imaging and pharmacokinetics were performed following I-124 codrituzumab. An ELISA assay was used to determine "cold" codrituzumab serum pharmacokinetics and compare it to that of I-124 codrituzumab. Correlation of imaging results was performed with IHC. Short-term safety assessment was also evaluated.
Results
Thirteen patients had tumor localization on baseline I-124 codrituzumab; heterogeneity in tumor uptake was noted. In three patients undergoing repeat imaging while on immunotherapy/sorafenib, evidence of decreased I-124 codrituzumab uptake was noted. All three patients who underwent imaging after progression while on immunotherapy continued to have I-124 codrituzumab tumor uptake. Pharmacokinetics of I-124 codrituzumab was similar to that of other intact IgG. No significant adverse events were observed related to the I-124 codrituzumab.
Conclusions
I-124 codrituzumab detected tumor localization in most patients with HCC. Pharmacokinetics was similar to that of other intact iodinated humanized IgG. No visible cross-reactivity with normal organs was observed.
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I-124 codrituzumab imaging and biodistribution in patients with hepatocellular carcinoma
Abstract
Background
I-124 codrituzumab (aka GC33), an antibody directed at Glypican 3, was evaluated in patients with hepatocellular carcinoma (HCC). Fourteen patients with HCC underwent baseline imaging with I-124 codrituzumab (~ 185 MBq, 10 mg). Seven of these patients undergoing sorafenib/immunotherapy with 2.5 or 5 mg/kg of cold codrituzumab had repeat imaging, with co-infusion of I-124 codrituzumab, as part of their immunotherapy treatment. Three patients who progressed while on sorafenib/immunotherapy were re-imaged after a 4-week washout period to assess for the presence of antigen. Serial positron emission tomography (PET) imaging and pharmacokinetics were performed following I-124 codrituzumab. An ELISA assay was used to determine "cold" codrituzumab serum pharmacokinetics and compare it to that of I-124 codrituzumab. Correlation of imaging results was performed with IHC. Short-term safety assessment was also evaluated.
Results
Thirteen patients had tumor localization on baseline I-124 codrituzumab; heterogeneity in tumor uptake was noted. In three patients undergoing repeat imaging while on immunotherapy/sorafenib, evidence of decreased I-124 codrituzumab uptake was noted. All three patients who underwent imaging after progression while on immunotherapy continued to have I-124 codrituzumab tumor uptake. Pharmacokinetics of I-124 codrituzumab was similar to that of other intact IgG. No significant adverse events were observed related to the I-124 codrituzumab.
Conclusions
I-124 codrituzumab detected tumor localization in most patients with HCC. Pharmacokinetics was similar to that of other intact iodinated humanized IgG. No visible cross-reactivity with normal organs was observed.
http://ift.tt/2D2oRup
CD137L dendritic cells induce potent response against cancer-associated viruses and polarize human CD8 + T cells to Tc1 phenotype
Abstract
Therapeutic tumor vaccination based on dendritic cells (DC) is safe; however, its efficacy is low. Among the reasons for only a subset of patients benefitting from DC-based immunotherapy is an insufficient potency of in vitro generated classical DCs (cDCs), made by treating monocytes with GM-CSF + IL-4 + maturation factors. Recent studies demonstrated that CD137L (4-1BBL, TNFSF9) signaling differentiates human monocytes to a highly potent novel type of DC (CD137L-DCs) which have an inflammatory phenotype and are closely related to in vivo DCs. Here, we show that CD137L-DCs induce potent CD8+ T-cell responses against Epstein–Barr virus (EBV) and Hepatitis B virus (HBV), and that T cells primed by CD137L-DCs more effectively lyse EBV+ and HBV+ target cells. The chemokine profile of CD137L-DCs identifies them as inflammatory DCs, and they polarize CD8+ T cells to a Tc1 phenotype. Expression of exhaustion markers is reduced on T cells activated by CD137L-DCs. Furthermore, these T cells are metabolically more active and have a higher capacity to utilize glucose. CD137L-induced monocyte to DC differentiation leads to the formation of AIM2 inflammasome, with IL-1beta contributing to CD137L-DCs possessing a stronger T cell activation ability. CD137L-DCs are effective in crosspresentation. PGE2 as a maturation factor is required for enhancing migration of CD137L-DCs but does not significantly reduce their potency. This study shows that CD137L-DCs have a superior ability to activate T cells and to induce potent Tc1 responses against the cancer-causing viruses EBV and HBV which suggest CD137L-DCs as promising candidates for DC-based tumor immunotherapy.
http://ift.tt/2FexurS
CD137L dendritic cells induce potent response against cancer-associated viruses and polarize human CD8 + T cells to Tc1 phenotype
Abstract
Therapeutic tumor vaccination based on dendritic cells (DC) is safe; however, its efficacy is low. Among the reasons for only a subset of patients benefitting from DC-based immunotherapy is an insufficient potency of in vitro generated classical DCs (cDCs), made by treating monocytes with GM-CSF + IL-4 + maturation factors. Recent studies demonstrated that CD137L (4-1BBL, TNFSF9) signaling differentiates human monocytes to a highly potent novel type of DC (CD137L-DCs) which have an inflammatory phenotype and are closely related to in vivo DCs. Here, we show that CD137L-DCs induce potent CD8+ T-cell responses against Epstein–Barr virus (EBV) and Hepatitis B virus (HBV), and that T cells primed by CD137L-DCs more effectively lyse EBV+ and HBV+ target cells. The chemokine profile of CD137L-DCs identifies them as inflammatory DCs, and they polarize CD8+ T cells to a Tc1 phenotype. Expression of exhaustion markers is reduced on T cells activated by CD137L-DCs. Furthermore, these T cells are metabolically more active and have a higher capacity to utilize glucose. CD137L-induced monocyte to DC differentiation leads to the formation of AIM2 inflammasome, with IL-1beta contributing to CD137L-DCs possessing a stronger T cell activation ability. CD137L-DCs are effective in crosspresentation. PGE2 as a maturation factor is required for enhancing migration of CD137L-DCs but does not significantly reduce their potency. This study shows that CD137L-DCs have a superior ability to activate T cells and to induce potent Tc1 responses against the cancer-causing viruses EBV and HBV which suggest CD137L-DCs as promising candidates for DC-based tumor immunotherapy.
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Associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white women diagnosed with breast cancer: the Breast Cancer Health Disparities Study
Abstract
Purpose
ALDH1A1, one of the main isotopes of aldehyde dehydrogenase-1 is involved in the differentiation and protection of normal hematopoietic stem cells and functions in alcohol sensitivity and dependence. We evaluated the associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white (NHW) breast cancer (BC) cases from the Breast Cancer Health Disparities Study.
Methods
Nine SNPs in ALDH1A1 were evaluated in 920 Hispanic and 1372 NHW women diagnosed with incident invasive BC. Adjusted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were stratified by Native American (NA) ancestry and alcohol consumption.
Results
A total of 443 deaths occurred over a median follow-up time of 11 years. After adjusting all results for multiple comparisons, rs7027604 was significantly associated with all-cause mortality (HRAA = 1.40; 95% CI 1.13–1.73, P adj = 0.018). The rs1424482 CC genotype (HRCC = 1.69; 95% CI 1.20–2.37, P adj = 0.027) and the rs7027604 AA genotype (HRAA = 1.65; 95% CI 1.21–2.26, P adj = 0.018) were positively associated with non-BC mortality. Among long-term light drinkers, rs1888202 was associated with decreased all-cause mortality (HRCG/GG = 0.36; 95% CI 0.20–0.64), while associations were not significant among non-drinkers or moderate/heavy drinkers (P interation = 0.218). The increased risk of all-cause mortality associated with rs63319 was limited to women with low NA ancestry (HRAA = 1.53; 95% CI 1.19–1.97).
Conclusions
Multiple SNPs in ALDH1A1 were associated with increased risk of mortality after BC. Future BC studies examining the relationship between ALDH1A1 and mortality should consider the modifying effects of alcohol consumption and NA ancestry.
http://ift.tt/2FrOTMY
Characterization of a novel germline BRCA1 splice variant, c.5332+4delA
Abstract
Purpose
Germline mutations in BRCA1 and BRCA2 confer a significant increase in risk for cancer, and determining pathogenicity of a BRCA variant can guide the clinical management of the disease. About 1/3 of BRCA1 variants reported in the public databases have uncertain clinical significance due to lack of conclusive evidence. This study aims to characterize a novel BRCA1 deletion affecting the + 4 splice donor site identified in an individual with early-onset breast cancer.
Methods
The effect of BRCA1 c.5332+4delA variant on RNA splicing was evaluated by amplifying regions of BRCA1 from cDNA derived from the patient. The proportion of abnormal transcript in the total transcripts was quantified. Loss of heterozygosity (LOH) in tumor tissue was investigated using Sanger sequencing and fragment analysis.
Results
BRCA1 c.5332+4delA caused skipping of exon 21 in patient-derived samples. Semi-quantitative analysis indicated that this aberrant RT-PCR product accounts for about 40% of the total transcript levels. Loss of heterozygosity (LOH) was observed in patient's tumor tissue.
Conclusions
Our results indicate that the BRCA1 c.5332+4delA variant contributes to cancer predisposition through disruption of normal mRNA splicing. We classify this variant as likely pathogenic.
http://ift.tt/2H5BaZt
Trends in progression-free survival (PFS) and time to progression (TTP) over time within first-line aromatase inhibitors trials in hormone receptor-positive advanced breast cancer
Abstract
Background
Over the last 20 years, aromatase inhibitors (AI) have been tested in clinical trials as first-line therapy for hormone receptor-positive (HR-positive) advanced breast cancer (ABC), firstly as experimental arms, when they proved to be effective, and recently as control arms. This analysis aims to evaluate trends in progression-free survival (PFS) and time to progression (TTP) over time.
Patients and methods
A literature review was conducted using the MEDLINE database to identify randomized controlled phase II or III trials which reported PFS or TTP of at least one arm using first-line AI HR-positive ABC patients. A linear correlation was used to access the association between the year of the first patient enrolled and the observed PFS/TTP.
Results
The search retrieved 19 trials, accounting for 4552 postmenopausal patients divided into 21 separate AI treatment arms. The PFS/TTP increased from 6 to 9 months in the earlier trials to 13–16 months in the current era, representing an absolute gain of approximately 7 months, without the addition of any other drug. Our analysis showed a positive correlation between the year of the first patient enrolled in these trials and median PFS/TTP reported (R 2 = 0.34; p < 0.01). No correlation was found between the year of the first patient included in these trials and other potential prognostic factors such as visceral metastasis at baseline (R 2 = 0.26; p = 0.20) or exposure to adjuvant therapy (R 2 = 0.05; p = 0.18).
Conclusion
Patients treated with first-line AIs in the more recently conducted trials have longer PFS/TTP when compared to their counterparts treated with the same drugs in older studies. These findings have important implications for the estimation of sample size and follow-up periods for the planning of future trials as well as in the translation of the results into clinical practice decisions.
http://ift.tt/2FsudEy
PRMT5 determines the sensitivity to chemotherapeutics by governing stemness in breast cancer
Abstract
Purpose
Acquired resistance to chemotherapeutic agents in breast cancer is a major clinical challenge. Recent studies have shown that the emergence of cancer stem cells contributes to the development of drug resistance, and the protein arginine methyltransferase 5 (PRMT5) was crucial for the maintenance of stemness. However, the roles of PRMT5 in breast cancer cell stemness and the development of cancer drug resistance have not been clarified. In this study, we investigated the effect of PRMT5 on the sensitivity to doxorubicin and cell stemness in breast cancer.
Methods
PRMT5 expression was assessed in a panel of breast cancer cell lines (MDA-MB-231, MCF7, T-47D, BT-474, Au-565) and normal mammal epithelial cells (MCF10A). For knockdown of PRMT5 expression, two pairs of shRNAs as well as a control shRNA were utilized. Meanwhile, the wild-type PRMT5 and its catalytically dead counterpart (R368A) were stably overexpressed in MDA-MB-231 and MCF7 cells. The sensitivity to doxorubicin was determined by MTT assays, TUNEL assays, and Western blot analyses. To evaluate the degree of cell stemness, CD24/CD44-sorting and mammosphere formation experiments were performed.
Results
We demonstrated that PRMT5 regulates OCT4/A, KLF4, and C-MYC in breast cancer to govern stemness and affects the doxorubicin resistance of breast cancer.
Conclusion
Our study suggests that PRMT5 may play an important role in the doxorubicin resistance of breast cancer.
http://ift.tt/2H2vdfZ
Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer
Abstract
Purpose
Although adjuvant polychemotherapy improves outcomes for early breast cancer, the significant variability in terms of pharmacokinetics results in differences in efficacy and both short and long-term toxicities. Retrospective studies support the use of dose tailoring according to the hematologic nadirs.
Methods
The SBG 2004-1 trial was a randomized feasibility phase II study which assessed tailored dose-dense epirubicin and cyclophosphamide (EC) followed by docetaxel (T) (group A), the same regimen with fixed doses (group B) and the TAC regimen (group C). Women aged 18–65 years, ECOG PS 0-1 with at least one positive axillary lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term toxicity have been previously published. Here, we report safety and efficacy data after 10 years of follow-up.
Results
A total of 124 patients were included in the study. After a median follow-up of 10.3 years, the probability for 10-year survival was 78.5, 75.1, and 63.4% and for relapse free survival 64.1, 71.0, and 59.5% for groups A, B, and C, respectively. There were no cases of clinically diagnosed cardiotoxicity or hematologic malignancies. No patient was lost to follow-up.
Conclusions
In this randomized phase II trial, tailored dose adjuvant chemotherapy was feasible, without an increased risk for long-term adverse events after a median follow-up of 10 years.
http://ift.tt/2FrOFFC
Trastuzumab combined with doublet or single-agent chemotherapy as first-line therapy for HER2-positive metastatic breast cancer
Abstract
Purpose
To investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC).
Methods
We searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766.
Results
The results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63–0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88–0.92, P < 0.0001). However, moderate-quality evidence revealed no significant difference between the two regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98–1.17, P = 0.157), which was confirmed by TSA, indicating that the cumulative Z-curve entered the futility area. Moderate-quality evidence indicated that treatment-related grade 3 or 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002), diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were observed more frequently with doublet CT+H than with single-agent CT+H.
Conclusions
Compared with single-agent CT, the combination of doublet CT with trastuzumab as first-line therapy for HER2-positive MBC is associated with longer PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore, doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good performance status.
http://ift.tt/2H85Fy5
The effect of post-progression survival on overall survival among patients with sensitive relapse of small cell lung cancer
Abstract
Recent studies have suggested that, among patients with advanced lung cancer, subsequent treatment after failure of first-line or second-line chemotherapy has a greater effect on overall survival (OS) than tumor shrinkage or progression-free survival (PFS). However, no studies have examined this issue among patients with sensitive relapse of small cell lung cancer (SCLC). We retrospectively evaluate 77 patients with sensitive relapse of SCLC who received second-line chemotherapy after first-line platinum doublet chemotherapy between January 1999 and November 2013. The analyses included patient characteristics, treatment parameters, tumor shrinkage, PFS, post-progression survival (PPS), and OS. Spearman rank correlation analysis and linear regression analysis revealed that PPS was strongly correlated with OS (r = 0.91, p < 0.01, R2 = 0.96), PFS was moderately correlated with OS (r = 0.58, p < 0.01, R2 = 0.28), and tumor shrinkage was weakly correlated with OS (r = 0.34, p < 0.01, R2 = 0.12). A multivariate Cox proportional hazards model with a stepwise regression procedure revealed that PPS was significantly associated with age at the start of second-line chemotherapy, best response to second-line and third-line chemotherapy, and the number of regimens after progression beyond second-line chemotherapy (p < 0.05). These findings suggest that PPS has a stronger effect than PFS on OS among patients with sensitive relapse of SCLC. Thus, response to second-line chemotherapy and subsequent treatment for disease progression after second-line chemotherapy may be important factors that influence OS.
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CD137L dendritic cells induce potent response against cancer-associated viruses and polarize human CD8 + T cells to Tc1 phenotype
Abstract
Therapeutic tumor vaccination based on dendritic cells (DC) is safe; however, its efficacy is low. Among the reasons for only a subset of patients benefitting from DC-based immunotherapy is an insufficient potency of in vitro generated classical DCs (cDCs), made by treating monocytes with GM-CSF + IL-4 + maturation factors. Recent studies demonstrated that CD137L (4-1BBL, TNFSF9) signaling differentiates human monocytes to a highly potent novel type of DC (CD137L-DCs) which have an inflammatory phenotype and are closely related to in vivo DCs. Here, we show that CD137L-DCs induce potent CD8+ T-cell responses against Epstein–Barr virus (EBV) and Hepatitis B virus (HBV), and that T cells primed by CD137L-DCs more effectively lyse EBV+ and HBV+ target cells. The chemokine profile of CD137L-DCs identifies them as inflammatory DCs, and they polarize CD8+ T cells to a Tc1 phenotype. Expression of exhaustion markers is reduced on T cells activated by CD137L-DCs. Furthermore, these T cells are metabolically more active and have a higher capacity to utilize glucose. CD137L-induced monocyte to DC differentiation leads to the formation of AIM2 inflammasome, with IL-1beta contributing to CD137L-DCs possessing a stronger T cell activation ability. CD137L-DCs are effective in crosspresentation. PGE2 as a maturation factor is required for enhancing migration of CD137L-DCs but does not significantly reduce their potency. This study shows that CD137L-DCs have a superior ability to activate T cells and to induce potent Tc1 responses against the cancer-causing viruses EBV and HBV which suggest CD137L-DCs as promising candidates for DC-based tumor immunotherapy.
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The effect of post-progression survival on overall survival among patients with sensitive relapse of small cell lung cancer
Abstract
Recent studies have suggested that, among patients with advanced lung cancer, subsequent treatment after failure of first-line or second-line chemotherapy has a greater effect on overall survival (OS) than tumor shrinkage or progression-free survival (PFS). However, no studies have examined this issue among patients with sensitive relapse of small cell lung cancer (SCLC). We retrospectively evaluate 77 patients with sensitive relapse of SCLC who received second-line chemotherapy after first-line platinum doublet chemotherapy between January 1999 and November 2013. The analyses included patient characteristics, treatment parameters, tumor shrinkage, PFS, post-progression survival (PPS), and OS. Spearman rank correlation analysis and linear regression analysis revealed that PPS was strongly correlated with OS (r = 0.91, p < 0.01, R2 = 0.96), PFS was moderately correlated with OS (r = 0.58, p < 0.01, R2 = 0.28), and tumor shrinkage was weakly correlated with OS (r = 0.34, p < 0.01, R2 = 0.12). A multivariate Cox proportional hazards model with a stepwise regression procedure revealed that PPS was significantly associated with age at the start of second-line chemotherapy, best response to second-line and third-line chemotherapy, and the number of regimens after progression beyond second-line chemotherapy (p < 0.05). These findings suggest that PPS has a stronger effect than PFS on OS among patients with sensitive relapse of SCLC. Thus, response to second-line chemotherapy and subsequent treatment for disease progression after second-line chemotherapy may be important factors that influence OS.
http://ift.tt/2D0huUn
Chronic lymphocytic leukaemia and spontaneous rupture of spleen
Pathological or spontaneous splenic rupture is a rare but well-recognised complication of haematological malignancies. The authors present a clinical report of a 78-year-old woman with known clinical history of chronic lymphocytic leukaemia and atrial fibrillation under anticoagulation with apixaban which has spontaneous splenic rupture. Pathological examination revealed lymph node and splenic infiltration due to chronic lymphocytic leukaemia. The diagnosis of splenic rupture must be considered in all patients with haematological malignancies who experience acute abdomen. Given the severity, it requires a correct and timely diagnosis.
http://ift.tt/2H8EzXv
Multiorgan failure associated with severe ovarian hyperstimulation syndrome due to inadequate protocol optimisation: a rare but avoidable complication
Ovarian hyperstimulation syndrome (OHSS) is a well-recognised iatrogenic complication following controlled ovarian stimulation (COS). Mild to moderate cases are mostly managed conservatively. Severe cases of OHSS can be potentially fatal. For this reason, UK clinics providing licensed fertility treatment are obliged to follow Human Fertilisation and Embryology Authority guidelines for reporting severe incidents. We present an unusually severe complication of OHSS resulting in significant morbidity. A nulligravida woman aged 25, with a 4-year history of subfertility and multiple risk factors for the development of OHSS, underwent COS. Immediately following oocyte retrieval, the patient developed symptoms of early-onset severe OHSS. The subsequent clinical deterioration of the patient precipitated multiple organ failure, including renal and hepatic dysfunction. Despite supportive management in an intensive care unit, the patient required transfer to a tertiary liver centre for specialist treatment. OHSS is a preventable complication; therefore, such an uncommon presentation of the syndrome provides important clinical lessons to be discussed.
http://ift.tt/2FsvawZ
Uncommon cause for chest pain
Description
A man aged 26 years presented with pain in the left side of the chest for 9 months, which was increasing on respiration and movement. However, patient did not have exertional dyspnoea, fever, skin lesions, history of trauma, weight loss or loss of appetite. On examination, patient had localised tender swelling on the lower part of left side of the chest with no other bony deformity or facial asymmetry. Chest X-ray posteroanterior view (figure 1) revealed radioluscent expansile lytic lesion in the left eighth rib. Clinical biochemistry revealed an elevated alkaline phosphatase at 224 U/L (normal: 40–125), calcium 9.5 mg/dL (normal: 8.3–10.4), phosphate 4 mg/dL (normal: 2.5–4.6) and 25-hydroxyvitamin-D 28 ng/mL (normal: 30–75). Tc99m-labelled methylene diphosphonate bone scan (figure 2) revealed increased tracer uptake only in the left eighth rib. The biopsy of the affected rib was performed which on histopathological examination (figure 3) showed irregular...
http://ift.tt/2H3jr56
Eyes that cannot be seen: a rare case of ankyloblepharon filiforme adnatum (AFA) in a neonate
Description
An infant aged 17 days was presented to our clinic with inability to open both eyes along with facial deformity. The vitals were found to be normal and no other systemic abnormality was recorded. On ocular examination, the child was found to have bilateral ankyloblepharon along with cleft lip and cleft palate. An urgent examination was done under general anaesthesia which revealed ankyloblepharon involving bilateral eye (figure 1A) barring a small area on the medial aspect of both eyelids. A probe was passed from the small opening on both sides which revealed no adhesions between the lids and the underlying ocular structures (figure 1B). The patient was diagnosed as having ankyloblepharon filiforme adnatum (AFA) and the lids were separated gently with the help of Westcott scissors. The bare lid margins (figure 1C) were apposed using continuous 8-0 Vicryl sutures. At the...
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Uncommon skin cancer: pleomorphic dermal sarcoma
Descriptions
An 86-year-old man presented to the dermatology clinic with a 10-week history of lesion on the vertex of his scalp. This had been intermittently crusting and bleeding but was non-tender and not enlarging. The patient had a background of two previous squamous cell skin carcinomas of his right shoulder and left ear. With regards to his sun exposure, he had previously served in the armed forces and had been posted to hot countries. On physical examination there was a 9x13 mm raised lesion with an overlying crust and rolled edges on the scalp vertex (see figure 1A,B). There was no evidence of cervical lymphadenopathy. Clinical suspicion was that of a keratoacanthoma or squamous cell carcinoma, given the patient's background. A 4 mm cutaneous punch biopsy was organised on the fast-track pathway.
Figure 1
(A, B) Close-up of the scalp lesion.
Histological...
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The mass effect of a slowly growing GIST
Gastrointestinal stromal tumours (GISTs) are typically defined as solid masses arising from the GI tract, most commonly from the stomach and small intestine. They seldom present in a cystic form. Management of cystic masses arising from the GI tract may pose a diagnostic predicament. We had one such case that presented itself with complaints of a slow growing intra-abdominal mass. An ultrasound scan demonstrated a thick-walled cystic lesion arising from the pelvis. Further imaging evaluations in the form of a CT scan revealed a complex large cystic mass arising from left upper quadrant (see Figure 1). Due to the uncertainty of origin of this mass and lack of invasion or lymphadenopathy, it was thought to be benign. After a multidisciplinary meeting, it was concluded that an urgent surgical excision of this benign mass was the best treatment. The surgical treatment of which entailed a 10 hours surgery to resect this 10 kg lesion, which comprised 7 L fluid and 3 kg solid mass. Histopathology aided in the diagnosis of this lesion as a CD117-positive and DOG1-positive GIST.
http://ift.tt/2FpC99z
IgG4-related autoimmune pancreatitis complicated by splenic artery pseudoaneurysm
Description
A 65-year-old man presented with a 1-year history of swelling of the submandibular salivary glands bilaterally. Blood tests revealed C-reactive protein (CRP) level of 0.28 mg/L, leucocyte count of 5.22x109/L (neutrophil count 3.07x109/L), haemoglobin level of 13.1 g/dL and platelet count of 234x109/L. Serum IgG and IgG4 levels were 2054 mg/dL (normal 861–1747) and 540 mg/dL (4.8–105), respectively. Biopsy of the right submandibular gland revealed a dense lymphoplasmacytic infiltrate and storiform fibrosis with increased IgG4-positive plasma cells (IgG4:IgG ratio 67%). Contrast-enhanced CT (CE-CT), which was performed to evaluate other sites of involvement, showed diffuse enlargement of the pancreas with a capsule-like rim (figure 1A). A diagnosis of IgG4-related sialadenitis and autoimmune pancreatitis was made. The patient had no abdominal complaints or jaundice, and he was followed up with careful observation.
Figure 1
Contrast-enhanced CT on presentation (A) and after 1 year of observation (B) showing diffuse enlargement of...
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Metastatic MSSA infection of the spine and extremities
Here, we present a rare case of metastatic methicillin sensitive Staphylococcus aureus (MSSA) infection arising from an unknown focus and spreading throughout the lumbar spine with associated pyomyositis of the paraspinal musculature, and septic arthritis of the knee, ankle and sternoclavicular joint. This case highlights the potential for missed aspects and delay in diagnosis in the care of metastatic S. aureus and the need for multispecialty intervention. Treatment of S. aureus infections requires a high index of suspicion and careful examination of multiple organ systems to identify the full extent of the disease. A discussion on metastatic S. aureus infection follows the report.
http://ift.tt/2FrImSs
Beating the odds: a rare case of supracardiac total anomalous pulmonary venous return (TAPVR) in an adult patient
Total anomalous pulmonary venous return (TAPVR) is a rare congenital heart defect, and patients are usually symptomatic at a very young age. Survival to adulthood without surgical correction is extremely rare. We report a 33-year-old woman with a heart murmur and a history of a successful pregnancy. Echocardiogram revealed a large atrial septal defect with suspicious pulmonary vein anomaly. Chest radiograph demonstrated classical 'snowman' configuration. Cardiac catheterisation was consistent with anomalous pulmonary venous drainage. Cardiac CT confirmed supracardiac TAPVR, whereby all the pulmonary veins drain into the anomalous vein and finally to the superior vena cava. She remained asymptomatic and underwent a successful surgical repair.
http://ift.tt/2H5GMmA
Blue nails: window to micronutrient deficiency
Description
A 12-year-old boy presented with progressive darkening of nails of both hands and feet for the past 3 months. He noticed the blue-black pigmentation of all the fingernails and toenails (figure 1A,B). Pigmentation was more marked in fingernails, particularly over thumbnails (figure 1C,D). The pigmentation started proximally and progressed distally. It was associated with hyperpigmentation of distal phalanges and nail bed. There was no history of any exposure to dyes or work in factory, trauma or exposure to any other agents. There was no history of dermatitis or rash prior to this complaint. He was a non-vegetarian. Other systemic examination was unremarkable.
Figure 1
Hyperpigmentation of nails. Blue-black pigmentation of all the fingernails and toenails (A,B) with associated hyperpigmentation of nail bed, distal phalanges and knuckles. It is more marked on thumbs and great toes (C,D).
Lab...
http://ift.tt/2Fr1AYv
Unusual cause of neck pain
Description
A 69-year-old man with hyperlipidaemia presented to the emergency department with a 4-day history of new onset pain in the neck. The pain was severe (rated 9/10 in severity), constant, localised to the base of the skull and was associated with significant restriction of neck motion; any movements resulted in dramatic worsening of the pain. He also reported subjective fevers at home. He did not report trauma, photophobia, phonophobia, nausea, vomiting, insect bites, visual disturbances, trouble swallowing or speaking, jaw claudication or morning stiffness. There were no sick contacts. He did not have pain at any other sites. He had tried some topical diclofenac gel for the past 2 days without much relief. His only scheduled medication was atorvastatin.
On physical examination, his temperature was 38.1°C, blood pressure was 128/82 mm Hg, heart rate was 82/min and respiratory rate was 14/min. He was visibly trying not to move...
http://ift.tt/2H5ackI
The forgotten electrolyte, when hypercalcaemia manifest as gait instability and altered mental status
An altered mental status presents a diagnostic challenge for many clinicians. Described here is a case of primary hyperparathyroidism not initially suspected until after a thorough neurological and infectious cause were excluded. A 60-year-old woman presented with altered mental status and gait instability. Her family noticed progressive gait instability and mood swings for the past 4 months. Initial imaging and laboratory values were unable to explain her symptoms. On transfer out of the intensive care unit, her corrected calcium was found to be 13.3 mg/dL with an elevated parathyroid hormone. Her hypercalcaemia was refractory to medical management. Ultrasound found a 2 cm nodule, which was surgically removed and found to be a parathyroid adenoma. Her calcium normalised and neurological deficits subsided. Hypercalcaemia can lead to a constellation of symptoms that include the classical 'stones, bones, abdominal moans and psychic groans' and electrolyte derangements should be considered in the differential of altered mental status.
http://ift.tt/2Fr1m3B
'Pseudo-calcifications: detection of perfluorocarbon residue on a computed tomography scan 15 years after liquid ventilation therapy at 3 months of age
Partial liquid ventilation using perfluorocarbons is a therapy that was once frequently used in paediatric populations for patients with severe respiratory distress. Perfluorocarbon is a non-toxic, insoluble and radiopaque vector through which improved gas exchange can occur. Two previous cases have been reported of persistent perfluorocarbon residua, identified on imaging years after receiving liquid ventilation therapy. We report a case of perfluorocarbon detection on a CT scan 15 years after liquid ventilation at 3 months of age, and propose the probable mechanism of its appearance. The importance of considering the imaging appearances of 'pseudo-calcifications' as a long-term sequela to perfluorocarbon liquid ventilation is emphasised.
http://ift.tt/2H5MiFM
Following leads: connecting dysphagia to mixed connective tissue disease
Mixed connective tissue disease (MCDT) is a rare condition characterised by the presence of high titres of anti-U1 ribonucleoprotein antibodies and selected clinical features of systemic lupus erythematosus, systemic sclerosis and polymyositis/dermatomyositis. Early symptoms are non-specific, including easy fatigability, myalgia, arthralgia and Raynaud's phenomenon. Some reports emphasised the favourable outcome and excellent response to glucocorticoids, but there are contradictory studies reporting worse prognosis. Also, a subset of patients evolve into a clinical picture more consistent with a major diffuse connective tissue disease. We present the case of a 50-year-old black woman whose inaugural presentation of MCDT was oropharyngeal dysphagia, symmetrical proximal muscle weakness, tongue atrophy and skin sclerosis. High-dose corticosteroids and methotrexate were given with little improvement, maintaining disabling dysphagia leading to a percutaneous endoscopic gastrostomy tube placement. She was then started on intravenous immunoglobulin with progressive remission of symptoms.
http://ift.tt/2FoB0iF
Methylprednisolone-induced acute liver injury in a patient treated for multiple sclerosis relapse
Drug-induced liver injury is the fourth most common cause of liver disease in industrialised countries. Methylprednisolone is often considered to be a treatment with a low hepatotoxicity. We report a case of methylprednisolone-induced liver injury in a 35-year-old woman. She was admitted to our department for acute liver injury 2 months after a treatment with high dose of methylprednisolone (1 g/day) for a multiple sclerosis relapse. No other cause of liver injury could be found (screening for hepatotropic viruses, autoimmune antibodies, ceruloplasmin, abdominal ultrasonography and liver biopsy). Liver function tests spontaneously improved and returned to normal range within 6 weeks. We also performed a brief review of the literature and identified 12 other cases of methylprednisolone-induced liver injury in patients treated for multiple sclerosis relapse. An immune rebound phenomenon could be responsible for rare but true hepatotoxicity of high-dose methylprednisolone therapy.
http://ift.tt/2H5Mc0S
Delayed diagnosis of chronic postoperative sternal infection: a rare case of sternal tuberculosis
Sternal osteomyelitis secondary to mycobacterium tuberculosis (TB) is rare, with <1% of musculoskeletal TB cases reported. The recurrent scenario is unresolving infection and delayed diagnosis. A 75-year-old woman presented with a persistently discharging sternal wound 10 months after coronary artery bypass grafting. Multiple antibiotics, wound debridement and removal of sternal wires was attempted; however, progression to local osteomyelitis and sternoclavicular joint destruction occurred. Tissue biopsies were finally sent for mycobacterial culture testing positive for Mycobacterium tuberculosis. High index of suspicion is necessary for diagnosis of sternal tuberculosis, confirmed through timely microbiological investigations. MRI may identify soft-tissue and bone oedema characteristic of TB osteomyelitis. This patient had no TB risk factors. The source of infection is unclear and warrants further investigation. Sternal TB osteomyelitis is uncommon and largely reported through case reports, thus management and indications for surgery remain undefined. If sensitive, standard TB four-drug regimen may be trialled.
http://ift.tt/2FqZs2S
Encephalopathy in an adult with cat-scratch disease
We report the case of a 53-year-old healthy man, presenting with confusion. The patient had been clinically diagnosed with cat-scratch disease (CSD) and prescribed a 10-day course of doxycycline orally. Approximately a week after he had completed the treatment, he was admitted to our department with confusion. Neurological examination revealed expressive dysphasia with no motor or sensory deficits. Cerebrospinal fluid (CSF) examination showed only increased content. Imaging with CT and MRI of the brain did not reveal any abnormalities, and funduscopy was normal. Serology confirmed Bartonella henselae infection. CSD-associated encephalopathy was confirmed based on the clinical manifestations, CSF findings and positive serology. The patient was treated with a combination of doxycycline and rifampin and he rapidly improved with complete neurological recovery within 7 days. Encephalopathy is an unusual manifestation of CSD in adults with excellent prognosis.
http://ift.tt/2H6b4FU
Stroke thrombolysis complicated by ST elevation myocardial infarction (STEMI)
An 84-year-old male Jehovah's Witness presented to the emergency department 1 hour after onset of left facial droop and left upper limb weakness. Thrombolytic stroke treatment was commenced as per local thrombolytic protocol with intravenous recombinant tissue plasminogen activator (rtPA) at 2 hours and 25 min following onset of symptoms. Almost immediately after rtPA infusion the patient reported chest pain and had ECG changes consistent with a diagnosis of anterior ST elevation myocardial infarction. At angiogram, a graft study showed severe native coronary artery disease. The left internal mammary artery graft was patent to the left anterior descending artery (LAD); however, the apical LAD was occluded, with the appearance suggestive of embolic occlusion.
http://ift.tt/2FpjBXa
Placental abruption after amnioreduction for polyhydramnios caused by chorioangioma
Placental chorioangioma is the most common type of a benign placental tumour that occurs in 1% of pregnancies. A large chorioangioma is associated with adverse pregnancy outcomes. We present a case of placental abruption necessitating preterm delivery after multiple amnioreductions for polyhydramnios caused by a large chorioangioma. If antenatal diagnosis of a significant chorioangioma is made as the cause of polyhydramnios, caution should be taken when performing rapid amnioreductions.
http://ift.tt/2H5LSPI
More, less or both?
A 67-year-old Caucasian woman with no prior medical history was admitted to our hospital with complaints of generalised weakness, nausea, diarrhoea and weight loss. The patient suffered from tachycardia and hypotension. Blood tests revealed Graves' thyrotoxicosis and the patient was treated accordingly. However, patient's health continued to decline rapidly and further tests revealed a concomitant Addisonian crisis. Additional treatment with corticosteroids led to a full recovery. It is well known that autoimmune endocrine disorders tend to cluster. However, the presentation is usually sequential in time. This case reports the highly rare simultaneous presentation of Addison's disease and Graves' thyrotoxicosis. It also provides several suggestions to help establish the diagnoses.
http://ift.tt/2Fr04Wn
Crosstalk between VEGFR and other receptor tyrosine kinases for TKI therapy of metastatic renal cell carcinoma
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and is frequently accompanied by the genetic features of von Hippel–Lindau (VHL) loss. VHL loss increases the expression of hypoxia-inducible factors (HIFs) and their targets, including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). The primary treatment for metastatic RCC (mRCC) is molecular-targeted therapy, especially anti-angiogenic therapy. VEGF monoclonal antibodies and VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are the main drugs used in anti-angiogenic therapy. However, crosstalk between VEGFR and other tyrosine kinase or downstream pathways produce resistance to TKI treatment, and the multi-target inhibitors, HIF inhibitors or combination strategies are promising strategies for mRCC. HIFs are upstream of the crosstalk between the growth factors, and these factors may regulate the expression of VEGR, EGF, PDGF and other growth factors. The frequent VHL loss in ccRCC increases HIF expression, and HIFs may be an ideal candidate to overcome the TKI resistance. The combination of HIF inhibitors and immune checkpoint inhibitors is also anticipated. Various clinical trials of programmed cell death protein 1 inhibitors are planned. The present study reviews the effects of current and potential TKIs on mRCC, with a focus on VEGF/VEGFR and other targets for mRCC therapy.
http://ift.tt/2I75PHm
Brain Connectivity and Cognitive Flexibility in Nonirradiated Adult Survivors of Childhood Leukemia
Abstract
Background
This study aimed to assess functional and structural brain connectivity in adult childhood leukemia survivors and the link with cognitive functioning and previously identified risk factors such as intrathecal methotrexate dose and age at start of therapy. Methods
Thirty-one nonirradiated adult childhood leukemia survivors and 35 controls underwent cognitive testing and multimodal magnetic resonance imaging (resting state functional MRI, T1-weighted, diffusion-weighted, and myelin water imaging [MWI]). Analyses included dual regression, voxel-based morphometry, advanced diffusion, and MWI modeling techniques besides stepwise discriminant function analysis to identify the most affected executive cognitive domain. Correlations with discrete intrathecal MTX doses and (semi)continuous variables were calculated using Spearman's rank and Pearson's correlation, respectively. All correlation tests were two-sided. Positive and negative T-contrasts in functional and structural MRI analysis were one-sided. Results
Survivors demonstrated lower functional connectivity between the default mode network (DMN) and inferior temporal gyrus (ITG; P < .008). Additionally, we observed higher fractional anisotropy (FA; P = .04) and lower orientation dispersion index (ODI; P = .008) at the left centrum semiovale, which could—given that several fiber bundles cross this region—suggest selective reduced integrity of the respective white matter tracts. Set shifting reaction time, a measure of cognitive flexibility, was mostly impaired and correlated with lower FA (r = –0.53, P = .003) and higher ODI (r = 0.40, P = .04) in survivors but not with DMN-ITG connectivity. There were no statistically significant differences between survivors and controls in WM or GM volume, nor was there a statistically significant correlation between imaging measurements and age at start of therapy or intrathecal methotrexate dose. Conclusions
Adult, nonirradiated childhood leukemia survivors show altered brain connectivity, which is linked with cognitive flexibility.http://ift.tt/2thQaSa
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