tbuckley/cabot-search huggingface dataset:
Genetic predisposition to childhood cancer: A retrospective cohort analysis in a multidisciplinary genetic cancer counseling Unit.
Authors: Nuria Rodriguez Salas, Adela Escudero, Naiara Blanco, Dolores Corral, Oliver Higuera, Leticia Ruiz Gimenez, Alejandro Gallego, Darío Sánchez Cabrero, Laura Rodriguez, Antonio Perez Martinez
Journal: Journal of Clinical Oncology (2020)

e13643 Background: The incidence of childhood cancer in Spain is 18, 2 cases per 100.000 inhabitants per year. The presence of predisposing genetic factors has been revealed in approximately 10% of patients, in them the detection of genetic mutations associated is essential in order to establish the correct clinical management of patients and their relatives. However, genetic counseling in this population is currently underestimated since, not all patients with pediatric malignancies have a family history of cancer or other clinical signs to suspect and inheritance syndrome. Methods: The Unit for Predisposition to Child and Adolescent Cancer of the University Hospital La Paz in Madrid, Spain, is composed by the Units of Clinical Oncology, Pediatric Hemathology-Oncology, and Genetics. Inclusion criteria are based on the characteristics of the individual's neoplasia, family characteristics and other phenotypic characteristics.The molecular study is carried out through Next Generation Sequencing, Direct Sequencing and / or MLPA. In the present study, a retrospective and descriptive analysis of the cases studied from September 2018 to December 2019 was carried out. Results: The Pediatric Cancer Predisposition Functional Unit of the La Paz University Hospital attended during the years 2018 and 2019 a 58 patients with suspected predisposition syndromes to childhood cancer belonging to 41 families. The following inheritance syndromes have been identified: hereditary retinoblastoma in 14 families with mutation in the RB1 gene, Li Fraumeni syndrome in 1 family with mutation in the TP53 gene, multiple endocrine neoplasia type 2A by RET gene mutation in 1 family, 1 hereditary melanoma syndrome with a CDKN2A mutation, and inheritance family leukemia in 1 family with a PAX5 gene mutation. Other cases studied have been negative-non informative, with the following neoplasms of the index cases: unilateral retinoblastoma, hepatoblastoma, hamartomatous colon polyposis, lymphoma, leukemia and soft tissue sarcoma. In addition to the molecular diagnosis of the index case, both cases and family members received genetic counseling and adequate clinical management, adapted to each syndrome. Conclusions: The multidisciplinary and specialized approach improves the diagnosis and monitoring of patients with suspected syndromes of predisposition to childhood cancer and allows the establishment of prevention strategies and early diagnosis individualized to each family.
Metabolic coessentiality mapping identifies C12orf49 as a regulator of SREBP processing and cholesterol metabolism
Authors: Erol C. Bayraktar, Konnor La, Kara Karpman, Gokhan Unlu, Ceren Ozerdem, Dylan J. Ritter, Hanan Alwaseem, Henrik Molina, Hans-Heinrich Hoffmann, Alec Millner, G. Ekin Atilla-Gokcumen, Eric R. Gamazon, Amy R. Rushing, Ela W. Knapik, Sumanta Basu, Kıvanç Birsoy
Journal: Nature Metabolism (2020)
血脂异常的临床评价
Authors: 韩小茜
Journal: BMJ (2007)

血脂是临床重要的诊断指标,广泛应用于动脉粥样硬化性心脑血管病的防治及其他诸多临床相关专业疾病中[1-2].对于血脂水平划分、影响因素、测定方法、临床意义等许多问题需要引起广大医疗技术人员的关注。
Breast cancer: The Indian scenario.
Authors: Ajay Gogia, Svs Deo, Dayanand Sharma, Sandeep Mathur
Journal: Journal of Clinical Oncology (2020)

e12567 Background: This study was undertaken to evaluate the clinic-pathological characteristics and outcome of patients with female breast cancer at I.R.C.H, AIIMS, New Delhi, one of the largest tertiary-care cancer center in India. Methods: This ambispective study included patients with breast cancer in females, registered at our institute from January 1st, 2014 to December 31st, 2018.We retrieved data from prospectively maintained clinical case records. Results: We included 997 patients with median age of 47.5 years (21–90) The TNM (AJCC-7th edition) stage distribution was stage I, 40 (4.01%); stage II, 326 (32.70%); stage III, 419 (42.02%); and stage IV, 212 (21.26%). The median tumour diameter was 5 cm. Infiltrating ductal carcinoma (96%) was the most common histologic subtype. Fifty eight percent of cases were positive for ER or/ and PR whereas 30.89% patients were HER2/neu positive. Triple negativity was found in 29.88 % of cases. Patients underwent breast conserving surgery in 28.2% of cases, 41.7% were received neo-adjuvant chemotherapy and 9.5 % of patients offered palliative chemotherapy. The pathological complete response was seen in 20.5% of cases. Loco-regional recurrence occurred in 2.8%, and 23.2% of patients developed distant metastases. The discordance of receptor was present in 20.5% for ER, 25.1% for PR, and 15 % for HER2/neu on re-biopsy at the time of relapse . Only 37.83% of the eligible patients received trastuzumab upfront. For non- metastatic group, the median time of relapse was 36 months, 3 year relapse free survival (RFS) was 73.5% and overall survival (OS) was 82.1% . Clinical stage(stage III), triple negativity and HER2 neu positivity were associated inferior RFS however pathological node involvement (HR 1.4, 95% CI 1.01–2.18, p = 0.01) and triple negativity (HR 1.9, 95% CI 1.36–2.90, p = 0.001) were associated with poor OS . For metastatic group, the median time of progression was 18 months and 3 year progression free survival (PFS) was 35% and OS was 20%. More than 2 sites of metastasis, upfront brain metastasis, triple negativity, and poor performance status (ECOG III/IV) were associated with inferior survival. Conclusions: This is one of the largest comprehensive data from a single center. Majority of our patients are younger in age, advance in stage, aggressive in biology and unaffordability of targeted therapy on eligible patients might lead to poor overall outcome. Triple negativity is found in around 30% of cases and associated with poor survival.
"Does better understanding of cancer care needs impact outcomes...?" The experiences of the Kigali City Cancer Challenge innovation.
Authors: Christian Ruchaho Ntizimira
Journal: Journal of Clinical Oncology (2020)

e19016 Background: Launched in January 2017 at the World Economic Forum in Davos, Switzerland, City Cancer Challenge (C/Can) is a multisectoral initiative supporting cities to take the lead in the design, planning, and implementation of cancer treatment solutions. C/Can serves as a unique platform to increase the number of people with access to quality cancer care in cities through a truly multisectoral approach. With access to both technical and financial resources, cities are supported to strengthen their capacity, leadership, and accountability in the delivery of cancer care, and engage in the design and implementation of cancer treatment and care solutions that meet the needs of their population. In 2018 during the World Health Assembly, the City of Kigali has been selected as the first African City Cancer Challenge alongside with Porto-Alegre from Brazil. Methods: The Needs Assessment questionnaire was designed to provide in-depth information on the delivery of cancer treatment and care services in a city. The objective is to generate systematic and reliable data on the availability. Results: Conclusions: The Kigali C/Can has developed an innovative solution from adapted from Rwandan patients, by Rwandan patients and for Rwandan patients through a city process which include a multi-sectorial decision-makers that was not happened before. [Table: see text]
Relationship between insomnia and cognitive function in middle-aged and elderly patients
Authors: Yukun Hu, Ping Wang, Yue Jiang, Li Ma, Chen Wang
Journal: BMJ (2018)

Objective
To investigate the relationship between insomnia and cognitive function in middle-aged and elderly patients.


Methods
Patients aged ≥ 45 years visiting outpatient clinic of You′anmen Community Health Center from October 2016 to December 2016 were enrolled in the study. Among 850 participants there were 159 patients with persistent insomnia, 188 with paroxysmal insomnia (insomnia group) and 503 with normal sleep (normal sleep group) according to DSM-5 diagnostic criteria. The sleep quality and cognition were evaluated using Pittsburgh Sleep Quality Index(PSQI) and Montreal Cognitive Assessment(MoCA) and compared among 3 groups. Relationship between sleep quality and cognition, influencing factors of cognition were explored in this study.


Results
The total score and all sub-scores of PSQI in persistent insomnia group were higher than those in the normal sleep group. The total score of PSQI and all sub-scores (except hypnotic drugs and daytime dysfunction) of paroxysmal insomnia group were higher than those of normal sleep group. The total PSQI score and all sub-scores (except sleep disorders) of the persistent insomnia group were higher than those of the paroxysmal insomnia group. The total score of MoCA and the sub-scores of naming, attention, language, abstract thinking, delayed recall and orientation ability of the persistent insomnia group were lower than those of the normal sleep group (P<0.05). The language ability of paroxysmal insomnia group was lower than that of normal sleep group (P<0.05). The language ability of persistent insomnia group was lower than that of paroxysmal insomnia group (P<0.05). The total score of MoCA was negatively correlated with the total score of PSQI and sub-scores of sleep time and sleep efficiency (r=-0.162, -0.131, -0.190; P<0.05). Logistic regression analysis showed that age was a risk factor for cognitive impairment (β=0.038, P=0.000) and sleep efficiency was a protective factor for cognitive function (β=0.260, P=0.000).


Conclusion
The overall cognitive function of middle-aged and elderly patients with persistent insomnia is poor, the abilities of naming, attention, language, abstract thinking, delayed recall and orientation are decreased; and the cognitive function is associated with age and sleep efficiency.


Key words: 
Community health center; Insomnia; Cognitive function; Middle-aged and elderly people
Diagnosis and management of splenomegaly
Authors: 金玲娟, 吴天勤, 陈海飞
Journal: BMJ (2011)

脾肿大判断的金指标是脾脏的重量,正常成人的脾脏50～250 g,随着年龄的增长趋于减轻.但这种方法仅限于脾切除术后及尸检的患者,因此临床实用性不强.以前把左肋下可触及脾脏作为脾脏增大的一个依据,并广被认可;但有16%的可触及脾脏在影像上却评估为正常大小[1].尽管如此,因其存在一定的主观性,仅凭影像学依据诊断脾脏大小尚未被采纳[2]。
US oncologists' perception of the efficacy, safety, and willingness to prescribe biosimilar cancer therapies.
Authors: Cesar Galan, Kjel Andrew Johnson, Elisea Avalos-Reyes
Journal: Journal of Clinical Oncology (2020)

e15213 Background: Biosimilars are the fastest-growing class of therapeutic products in the United States and can offer treatment options that can potentially lower healthcare-related costs in cancer care. It is essential to know if an oncologist will use such products. Therefore, we assessed the expected biosimilar prescribing behaviors of practicing oncologists for the originator products Avastin, Herceptin, Rituxan and Neulasta. Methods: We conducted an online cross-sectional survey of 75 hospital affiliated (46.7%) and community-based (53.3%) oncologists in July 2019 and used a Likert scale rating of “Never,” “Seldom,” “Sometimes,” “Often” and Always.” Descriptive statistics and percentages are reported; the Chi-square test was used for between-group comparisons. Results: The majority of oncologists (62.7%) worked in a for-profit practice, with 38.7% of primary practices offering exclusive in-office dispensing. Physicians currently reported prescribing branded drugs often or always 76% of the time. When asked to rate biosimilars by quality, safety and effectiveness, over 70% of providers perceived these four biosimilars to be the same or near equivalent to the branded drug. When asked to report their expected likelihood of prescribing a biosimilar in the future, 60% of providers believed they would often or always prescribe a biosimilar. There was no difference in the providers’ current biosimilar prescription pattern by type of insurance plan. Provided financial equivalence, oncologists reported being more likely to prescribe a biosimilar to new patients (85.3%) compared to existing patients (69.3%) (p = 0.019). The top 3 drivers of using biosimilar cancer therapies are the patient’s out of pocket cost, value of reimbursement and cost to the practice; 61%, 51% and 52%, respectively for fee-for-service reimbursement and 69%, 44% and 61%, respectively for value-based reimbursement. When asked why providers would not switch from buy-and bill to white-bagging, control of the drug (41.3%) and financial benefit to the providers’ practice (40%) were the top 2 reasons. Conclusions: Biosimilars are expected to reduce drug expenditures in cancer care. While providers in this study found biosimilars to be safe and effective, they reported being less likely to prescribe these drugs when there is a potential for their practice to lose money and control of the drug. Payment models for biosimilars in cancer care must support practice economics.
Enhanced coping and self-efficacy in caregivers of hematopoietic stem cell transplant (HCT) recipients: Identifying mechanisms of a multimodal psychosocial intervention.
Authors: Madeleine Elyze, Jamie M. Jacobs, Ashley Nelson, Lara Traeger, Annemarie Jagielo, Joseph A. Greer, Jennifer S. Temel, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2020)

12122 Background: A brief multimodal psychosocial intervention (BMT-CARE) for caregivers of HCT recipients demonstrated promising efficacy for improving caregiver quality of life (QOL), mood, coping skills, and self-efficacy. We examined whether improvements in coping and self-efficacy mediated the intervention effects on QOL and mood. Methods: We conducted a randomized clinical trial of BMT-CARE for caregivers of patients undergoing autologous or allogeneic HCT at a single institution. Caregivers were randomly assigned to BMT-CARE or usual care. BMT-CARE was tailored to the HCT trajectory and integrated treatment-related education and self-care with cognitive-behavioral skills and caregiving-specific strategies to promote coping. Caregivers completed self-report measures of QOL (CareGiver Oncology QOL), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), coping skills (Measure of Current Status), and self-efficacy (Cancer Self-Efficacy Scale-Transplant) at enrollment and 60 days post-HCT. We used causal mediation regression models to examine whether changes in coping and self-efficacy mediated intervention effects on QOL, depression and anxiety symptoms. Results: Caregivers randomized to BMT-CARE reported improved self-efficacy (adjusted means: 156.20 vs. 147.06, P=0.023) and coping skills (adjusted means: 36.54 vs. 25.41, P&lt;0.001). Improved coping and self-efficacy partially mediated the intervention effects on 60-day QOL (indirect effect=6.93, SE=1.85, 95% CI [3.71, 11.05]). Similarly, improved coping and self-efficacy partially mediated reductions in 60-day depression and anxiety symptoms (indirect effect depression=-1.19, SE=0.42, 95% CI [-2.23, -0.53]; indirect effect anxiety=-1.46, SE=0.55, 95% CI [-2.52, -0.43]). Combined improvements in coping and self-efficacy accounted for 67%, 80%, and 39% of the total intervention effect on QOL and depression and anxiety symptoms, respectively. Conclusions: A brief multimodal intervention for caregivers of HCT recipients may improve QOL and mood by enhancing coping skills and self-efficacy. These findings offer important insights into the mechanisms by which caregiver-directed interventions may enhance caregiver QOL and reduce their psychological distress.
Mutation profile differences in younger and older patients with advanced breast cancer using circulating tumor DNA (ctDNA).
Authors: Katherine Clifton, Jingqin Luo, Yu Tao, Jennifer Saam, Thereasa A. Rich, Anna Roshal, Ashley Elizabeth Frith, Caron E. Rigden, Foluso Olabisi Ademuyiwa, Katherine N. Weilbaecher, Leonel Fernando Hernandez-Aya, Lindsay Leuthen Peterson, Nusayba Ali Bagegni, Rama Suresh, Mateusz Opyrchal, Ron Bose, Tanya Marya Wildes, Cynthia X. Ma
Journal: Journal of Clinical Oncology (2020)

1089 Background: Although the noninvasive nature of ctDNA testing is attractive in an older adult population, less is known regarding the mutation profiles of ctDNA in the older adult breast cancer population as this population is often excluded from studies. Previous tissue testing has shown differences in mutation profiles between older and younger adults with breast cancer. The objective of this study is to assess differences in mutation profiles in the older and younger adult breast cancer population using a ctDNA assay. Methods: Patients (pts) with advanced breast cancer underwent molecular profiling using a plasma-based ctDNA NGS assay (Guardant360) between 5/2015-10/2019 at Siteman Cancer Center. Clinicopathological histories were obtained from the medical record. The results of a multicenter database of pts with advanced breast cancer who had undergone molecular profiling using Guardant360 were obtained. Associations between mutations and age were measured using a Fisher’s exact test. Results: In the single institution cohort, of the 214 patients who underwent testing, 148 (69.16%) were &lt; 65 and 66 (30.84%) ≥ 65 years-old. The most frequently mutated genes in age &lt; 65 pts were TP53 (48.65%), PIK3CA (35.81%), and ESR1 (30.41%) while the most frequently mutated genes in age≥65 pts were PIK3CA (56.06%), TP53 (51.52%), ESR1 (25.76%), and ATM (21.21%). ATM, BRAF and PIK3CA mutations were found more frequently in age≥ 65 pts with ER+ HER2- breast tumors (p &lt; 0.01). MYC and ESR1 mutations were not significantly associated with age, overall or within subtype. Overall ctDNA resulted in change in management in 19.8% pts (40/202). In the larger multicenter cohort, of the 8803 pts who underwent testing, 5367 (61.0%) were &lt; 65 and 3417 (38.8%) ≥ 65 years-old. ATM, ESR1 and PIK3CA mutations were more common in age≥65 pts (p &lt; 0.0001) and MYC mutations were less common in age≥65 pts (p &lt; 0.0001). Conclusions: This study found that ctDNA is a feasible, attractive alternative to traditional biopsies and may identify actionable mutations in older adults with breast cancer. When controlling for subtype, results from a single institution were similar to the larger multicenter cohort showing ATM and PIK3CA were more common in the older adult population. This data suggests there may be additional molecular differences between breast cancer in older compared to younger adults that warrants further investigation.
Risk stratified multidisciplinary ambulatory management of malignant bowel obstruction (MAMBO) program for women with gynecological cancers: Preliminary results from a prospective single-center study.
Authors: Shiru Lucy Liu, Yeh Chen Lee, Nazlin Jivraj, Valerie Bowering, Lisa Wang, Gita Bhat, Ainhoa Madariaga, Lawrence Kasherman, Kashish Nathwani, Azieb Tesfu, Sarah Lee, Sarah E. Ferguson, Jennifer M. Croke, Catherine O'Brien, Jenny Lau, Tanya Chawla, Eran Schlomovitz, Amit M. Oza, Stephanie Lheureux
Journal: Journal of Clinical Oncology (2020)

6062 Background: Malignant Bowel Obstruction (MBO) is one of the most common and devastating complications in women with gynecological cancer (GC). There is currently no consensus guideline to improve patient (pt) care in this setting. MAMBO (NCT03260647) is an ongoing prospective study evaluating the clinical implementation of a novel management algorithm for multidisciplinary management of MBO in GC pts. We report preliminary patient outcomes. Methods: All GC pts at Princess Margaret Cancer Centre with a confirmed diagnosis of or are at risk of MBO are eligible for enrollment. Participants follow a low fiber diet titrated by severity of symptom and their monthly weight and albumin levels are recorded, along with standardized patient-reported outcome measures (PROMs) at different time points. For pts who develop MBO, inpatient and ambulatory management algorithms are applied using a multidisciplinary and interprofessional care model consisting of nurses, surgeons, oncologists, radiologists, nutritionists, total parenteral nutrition team, social work, and palliative care. Decisions regarding most optimal management strategies are made by this team with regular MAMBO rounds. A retrospective analysis of pts hospitalized with MBO between 2012 and 2017 was performed in order to have a historical comparison for outcome and survival analysis using Kaplan Meier methods. Results: Since August 2017, 70 pts have been enrolled in MAMBO. Most had high-grade serous ovarian carcinoma (75%), of whom 68% are platinum-resistant. So far, 36 (51%) developed MBO, 6 of whom had multiple sequential episodes. Mean number of days in hospital with MBO was 10 days (median 7, range 0-45), compared to 18 days (median 9, range 0-134) for historical control (p = 0.009). There was no significant loss in weight 6 months from MBO diagnosis but a significant reduction in albumin level by 2.75 g/L after 3 months (p = 0.005). PROMs suggest fatigue and general lack of wellbeing were the symptoms with highest distress. Most patients (78%) received chemotherapy following MBO and most received weekly paclitaxel (36%). Median time from first MBO to death was 219 days (95% CI: 101-not reached) for all-comers in MAMBO and 174 days (95% CI: 98-363) for MBO requiring hospitalization, compared to 108 days (95% CI: 79-160) for historical controls (p = 0.007 and p = 0.062, respectively). Conclusions: Patient care and outcomes from MBO seem to be improved in GC pts enrolled in MAMBO compared to historical controls. Clinical trial information: NCT03260647.