bluuebunny/crossref_metadata_2025 huggingface dataset:
Response rate and survival for patients with metastatic colorectal cancer from right-sided versus left-sided tumors, treated with first-line triplet chemotherapy with bevacizumab.
Authors: Bazarbashi Shouki , Omar Ayman , Aljubran Ali Husain , Alzahrani Ahmed M
Published: March 2017

801

Background: Recent data have shown that right sided colonic cancer represent a molecularly different class of tumors from the left sided ones with worse survival in patients treated with doublets systemic chemotherapy. We report the result of response and survival on patients treated with triplet chemotherapy according to the primary tumor location. Methods: Medical records of patients treated with triplet chemotherapy (capecitabine, oxaliplatin and irinotecan) in combination with bevacizumab on a prospective clinical trial (clinicaltrial.gov: NCT01311050), were retrospectively reviewed for the location of primary tumor. Right sided tumors: from cecum to hepatic flexure. Left sided tumors: from splenic flexure to and including the rectum. Transverse colon were excluded. Patients who had multiple primaries were considered right sided if at least one of them was right sided. Results: Fifty-three patients treated with above triplet therapy. Eleven were right sided and 42 were left sided. Characteristics for right vs left sided tumors were as follow: Median age: 46 (range 24-55 years) vs 53 ( 32-74 years), male: 5 (46%) vs 23 (55%), performance status 0-1: 9 (82%) vs 37 (88%), KRAS wild: 3 (27) vs 12 (29%), single metastatic site: 5 (46%) vs 14 (33%) and Prior adjuvant chemotherapy: none vs 6 (14%). Response rate (complete and partial) were 6 (54%) in right sided tumors and 24(57%) in left sided tumors. Progression free and overall survival for right sided tumors was 22 (95% confidence interval (CI) 12.3-31.7) and 22 months (95% CI 16.6-27.4) and for left sided tumors were 12 (95% CI 3.5-20.5) and 28 months (95% CI 22.7-33.2) respectively. Conclusions: First-line triplet chemotherapy with bevacizumab may overcome the poor prognosis of metastatic right sided colonic cancer. Clinical trial information: NCT01311050.
A phase 1b/2, open label, dose-escalation study of margetuximab (M) in combination with pembrolizumab (P) in patients with relapsed/refractory advanced HER2+ gastroesophageal (GEJ) junction or gastric (G) cancer.
Authors: Catenacci Daniel V.T. , Kim Sunnie S. , Gold Philip Jordan , Philip Philip Agop , Enzinger Peter C. , Coffie Joe , Schmidt Emmett V. , Baldwin Malcolm , Nordstrom Jeffrey L. , Bonvini Ezio , Wigginton Jon M. , Hochster Howard S. , Denlinger Crystal Shereen , Uronis Hope Elizabeth , Bendell Johanna C. , Kelly Ronan Joseph , Davidson-Moncada Jan Kenneth , Lockhart Albert C.
Published: March 2017

TPS219

Background: Prognosis for advanced HER2+ GEJ and G cancers remains poor, with median survival just beyond one year. Trastuzumab (T) in combination with chemotherapy is the initial treatment of choice, but therapeutic options targeting HER2 beyond T are poorly defined. M is an Fc-enhanced monoclonal antibody (Mab) to HER2 that recognizes with similar affinity the same epitope as T and whose Fc domain, compared to T, binds with increased affinity to the activating CD16A Fc-receptor (FcR) and decreased affinity to the inhibitory CD32B FcR. Preliminary data shows that M monotherapy has clinical activity against HER2+ tumors in GEJ and G cancer patients previously treated with T or other anti-HER2 agents. P is a Mab that blocks the interaction of the immune checkpoint molecule, PD-1, with its ligands, facilitating tumor cell elimination by releasing tumor-associated T cells from exhaustion. Monotherapy P has demonstrated remarkable and durable clinical activity in a Phase I study. Safety profiles of M and P are acceptable and non-overlapping. Methods: This study advances a chemotherapy free combination of M + P treatment for advanced HER2+ GEJ and G cancer patients. Enrolled patients will have relapsed/refractory HER2+ GEJ or G adenocarcinoma with measurable disease that has progressed on T plus first line chemotherapy. HER2+ (IHC 3+ or ISH+) will be confirmed by central review. Two dose levels of M (10mg/kg and 15mg/kg) and a fixed dose of P (200mg) will be evaluated for safety and tolerability. Patients will receive combination treatment once every 21 days for up to 24 months, until confirmed disease progression or intolerable toxicity. Dose expansion will enroll up to 60 patients, with 20 undergoing pre- and on-treatment biopsy. Response will be assessed every 6 weeks for the first 6 months and every 12 weeks thereafter per RECIST v1.1 and immune RECIST to account for response patterns observed with immunotherapies. Primary endpoint is ORR and duration of response, and secondary endpoints include PFS and OS. The study was initiated on January 2016 and is ongoing in North America and Asia. Clinical trial information: NCT02689284.
Exploratory study of intraperitoneal paclitaxel plus mFOLFOX6 for gastric cancer patients with peritoneal metastasis and inadequate oral intake.
Authors: Yoshida Shuntaro , Ishigami Hironori , Muro Kei , Kadowaki Shigenori , Tsuji Yasushi , Ohta Yumiko , Yamashita Hiroharu , Yamaguchi Hironori , Kitayama Joji ,   Japan Intraperitoneal Chemotherapy Study Group (JIPG)
Published: March 2017

TPS222

Background: Systemic chemotherapy with oral fluoropyrimidine and platinum is recommended for the first-line treatment for unresectable or recurrent gastric cancer in Japan. However, some patients with severe peritoneal metastasis cannot take oral medications because of obstruction or dysfunction of the gastrointestinal tract. FOLFOX is regarded as one of the candidates for the standard of care for gastric cancer, and is now being evaluated in clinical trials. Intraperitoneal (IP) paclitaxel (PTX) provides sustained high local concentrations, and its efficacy has been shown in ovarian and gastric cancer. We developed a regimen combining IP PTX with S-1/PTX, and the phase III trial comparing with S-1/cisplatin suggested efficacy of this regimen. Therefore, we designed a regimen combining IP PTX with mFOLFOX6, and started an exploratory study in gastric cancer patients with peritoneal metastasis and inadequate oral intake. Methods: This is a prospective, multicenter, single-arm phase I/II study. Eligibility criteria include: pathologically proven unresectable or recurrent gastric adenocarcinoma; peritoneal metastasis; inadequate oral intake; adequate bone marrow function; acceptable liver and renal function; ECOG performance status of 0-2 and age between 20-80 years. Patients undergo diagnostic laparoscopy and are implanted with an IP port in the subcutaneous space of the lower abdomen, with a catheter placed in the pelvic cavity. mFOLFOX6 is administered bi-weekly, and IP PTX 20 mg/m2 is administered through an IP port on days 1, 8 and 15. The treatment course is repeated every 4 weeks until disease progression or unacceptable toxicity. The primary endpoint is the 1-year overall survival rate. Secondary endpoints are progression free survival, time to treatment failure, response rate, negative conversion rate on peritoneal cytology and safety. Twenty medical institutions from all over Japan participate in this study, and 34 patients are to be enrolled in two years. Toxicity will be evaluated in the early stage, and the protocol will be reconsidered and revised if all of the first 3 or more than 2 of the first 6 patients develop dose-limiting toxicities. Clinical trial information: UMIN000019206.
Phase I study of defactinib combined with pembrolizumab and gemcitabine in advanced cancer.
Authors: Wang-Gillam Andrea , Lockhart Albert C. , Tan Benjamin R. , Suresh Rama , Singh Preet Paul , Lim Kian-Huat , Pedersen Katrina , Amin Manik A. , Hawkins William G. , DeNardo David G
Published: March 2017

TPS505

Background: Focal adhesion kinase (FAK) is consistently hyperactivated in pancreatic ductal adenocarcinoma (PDAC), and FAK signaling is a key driver in forming its fibrotic and proinflammatory tumor microenvironment. Inhibition of FAK signaling leads to significant reduction of pancreatic tumor growth in animal models. Indeed, tumors treated with FAK inhibitors displayed markedly reduced tumor fibrosis and decreased immunosuppressive myeloid cells. Furthermore, our preclinical work has demonstrated that FAK- and PD-1 inhibitors elicit significant tumor regression, and the maximal response was achieved by combining FAK- and PD-1 inhibitors with gemcitabine, suggesting the need for a cytotoxic agent to bolster antigen presentation (Jiang H et al, Nature Medicine 2016). Defactinib is an orally available, potent ATP-competitive, FAK inhibitor with a recommended phase II dose (RP2D) of 400 mg twice daily. Methods: Eligible patients will be treated according to the dose escalation schema. A 3+3 design is used until the first occurrence of dose-limiting toxicity, and then switches to a continuous assessment design. The study has an expansion portion (group A and B) at the RP2D. Group A includes metastatic PDAC patients who are stable at least 4 months on front-line nab-paclitaxel/gemcitabine, and group B includes metastatic PDAC patients progressed on ≥ 1 chemotherapy line. Key eligibility criteria include patients with advanced solid tumors (dose escalation portion) or advanced PDAC (expansion cohort); age ≥18 years; ECOG score ≤1; normal organ function; and no history autoimmunity. The primary endpoint is to determine the RP2D. Secondary endpoints include objective response rate, progression-free survival and overall survival. The exploratory endpoints include developing a molecular and immune signature for treatment response. This trial is actively enrolling and funded by Precision Medicine Research Associate and Barnes Jewish Foundation. Clinical trial information: NCT02546531. [Table: see text]
An open-label, randomized, controlled clinical trial to explore the curative effects between the treatment of capecitabine and andrographolide and the single capecitabine in the patients with pathological and/or histologic diagnosed unresectable, advanced, recurrent, and metastatic colorectal cancer.
Authors: Shu Yongqian , Sun Jing , Cai Peifen , Wang Weicheng , Han Xiao , Gu Yanhong
Published: March 2017

TPS819

Background: Colorectal cancer (CRC) is one of the most commonly diagnosed solid tumors worldwide. Current therapies for the treatment of CRC mainly comprise fluoropyromidine-based chemotherapies that are used individually or in combination with oxaliplatin or/with target therapy. Andrographolide, a natural diterpenoid from Andrographispaniculata, has been reported to exert antibacterial, antiviral, anti-inflammation and neuroprotectiveactivities. Our previous studies have proved that Andrographolide can inhibit tumor growth in mice at a relatively high dose(about 200 mg/kg).The aim of the study is to make a comparison of PFS, RR, and OS of the elderly CRC between the treatment of xeloda and andrographolide and the signal xeloda.We look forward to these findings highlight the potential possibility of using this natural, safe and relatively inexpensivecompound as potential adjunctive treatments in improving the overall treatment response of patients with CRC in future. Methods: This is an open-label, randomized, controlled clinical trial. Patients older than or equal to 65, by pathological and/or histologic diagnosed unresectable, advanced, recurrent andmetastatic CRC, will be enrolled. These patients’ tumors must be clearly measured by radiographic technology. All cases of chemotherapy patients randomly divided into two groups, experimental group (xeloda with andrographolide): xeloda: 1250mg/m2 , po bid, d1–14, q3w; andrographolide: 500mg, ivd qd, d1–14, q3w; control group (xeloda): 1250mg/m2, po bid, d1–14, q3w, 21d/cycle. After each 2 cycles, patients will be examined by imageological tests (CT and/or MRI) or tumour biomarkers (CEA and CA199) to estimate the curative effects. Until the tumor progression or after 6 cycles, patients will be removed from this study. PFS is set as the primary endpoint while secondary endpoints include overall survival (OS), overall response rate (ORR), and health-related quality of life (HRQoL). Recruitment has begun in Jan 2014 and about 52 patients has joined this study. Clinical trial information: NCT01993472.
Metabolic syndrome (MetS) after platinum-based chemotherapy (CHEM): A multicenter study of North American testicular cancer survivors (TCS).
Authors: Abu Zaid Mohammad Issam , Gathirua-Mwangi Wambui G. , Williams AnnaLynn , Fung Chunkit , Monahan Patrick O. , Feldman Darren R. , Hamilton Robert James , Vaughn David J. , Beard Clair , Cook Ryan , Althouse Sandra K. , El Charif Omar , Sesso Howard D. , Ardeshirrouhanifard Shirin , Einhorn Lawrence H. , Fossa Sophie D. , Travis Lois B. ,   For the Platinum Study Group
Published: March 2017

102

Background: Testicular cancer has an excellent prognosis since the introduction of platinum-based CHEM. However, several European studies report an excess of cardiovascular disease (CVD) in TCS. MetS is a cluster of cardiovascular risk factors that doubles CVD risk, with several European series noting a prevalence ranging from 13-39% in TCS. In the first large multi-center North American study of TCS, we examine the prevalence of and potential risk factors for MetS after modern CHEM (NCI R01 CA157823). Methods: Eligible TCS were <50 y at diagnosis and treated with only first line CHEM after 1990. TCS underwent physical exams, completed questionnaires regarding co-morbidities and health behaviors and had lipid panels, testosterone, and serum soluble cell adhesion molecule-1 (sICAM-1) measured. A single nucleotide polymorphism, rs523349 (V89L), in 5-α-reductase gene ( SRD5A2) previously suggested to associate with MetS in TCS was genotyped. MetS was defined as ≥3 of the following: hypertension (HTN), waist circumference ≥102 cm, triglycerides ≥150 mg/dL, HDL ≤40 mg/dL, and diabetes (Alberti et al, Circulation 2009). Controls (1:1) derived from the National Health and Nutrition Examination Survey were matched on age, race, and educational status. Results: We evaluated 486 consecutively enrolled TCS. Median age at evaluation was 38 y (range: 19-68). TCS had higher prevalence of HTN compared to controls (43% vs 31%, P < .01) but lower prevalence of low HDL (24% vs 35%, P < .01) and abdominal obesity (28% vs 40%, P < .01). Prevalence of MetS was comparable (21% TCS; 22% controls, P = .59). In multivariate analysis, age at evaluation (P < .01), serum testosterone <3.0 ng/mL (OR = 2.0, P = .005), and elevated sICAM-1 (OR for quartiles 2, 3, 4 vs lowest quartile: 2.7 (P = .01), 3.1 (P < .01), and 3.6 (P < .01), respectively) significantly correlated with MetS. The variant rs523349 (VL/LL) did not associate with MetS. Conclusions: One in 5 TCS treated with CHEM developed MetS. Providers should screen for MetS, adequately treat hypogonadism, HTN and hyperlipidemia, and encourage TCS to maintain a healthy lifestyle. Significant elevations in sICAM-1 underscore a role for inflammation in MetS.
Brentuximab-induced peripheral neuropathy: Risk factors and patient experiences.
Authors: Nagle Sarah , Strelec Lauren E. , Loren Alison W. , Landsburg Daniel Jeffrey , Nasta Sunita , Mato Anthony R. , Schuster Stephen J. , Svoboda Jakub
Published: March 2017

120

Background: Brentuximab vedotin (BV) is an immunoconjugate used in Hodgkin lymphoma (HL) and other CD30+ lymphomas. The dose-limiting adverse effect is peripheral neuropathy (BIPN). Predictors of BIPN, effect on outcomes, and the biopsychosocial impact are not well defined. Methods: We conducted a single institution, mixed-methods study of lymphoma patients (pts) who received BV between 1/2010 and 5/2016. A retrospective analysis was conducted in all pts; an open-ended survey was given to pts seen in the prior year. A univariate analysis examined the association between BIPN and potential predictors. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan Meier method. Survey data were analyzed qualitatively via a framework approach. Results: Eighty-nine pts were eligible: 56% were male, 54% had HL, 71% had prior neurotoxic drugs, 93% received single agent BV. The median number of BV doses was 5. Forty-three (48%) pts developed BIPN. It resolved completely in 14 (33%) pts at a median follow-up of 12 mo. The median time to resolution was 13 wks. BV therapy was altered in 21 (24%) pts due to BIPN. There was no difference in PFS (6 vs. 12 mo., p = 0.09) or OS (NR vs. 26 mo., p = 0.11) in pts who had therapy altered due to BIPN. Table 1 lists significant risk factors for BIPN. No additional factors investigated (age, sex, prior neurotoxic agent, underlying neuropathy, diabetes mellitus or BMI) increased risk for BIPN. Fourteen of the 18 (78%) surveyed pts reported BIPN. At a median follow-up of 24 mo., 10 (71%) pts reported ongoing symptoms. BIPN affected quality of life in 50% and work in 20% of pts. Despite significant symptoms from BIPN, all pts were satisfied with their decision to receive BV regardless of disease response. Conclusions: BIPN is a significant adverse event and may fail to resolve in a large subset of pts. Surveyed pts reported that the benefits of BV outweigh the risks. Changes in therapy due to BIPN occur, but this did not affect outcomes in our cohort. Clinicians should be aware of the risk for BIPN and educate pts accordingly. [Table: see text]
Long-term side effects of high-risk neuroblastoma survivors in a referral center in central Illinois.
Authors: Speckhart Beth , Antony Reuben , Fernandez Karen S.
Published: March 2017

129

Background: Neuroblastoma (NBL) is the most common extra-cranial solid organ malignancy in children. Although low and intermediate-risk patients have a survival of close to 90%, the same cannot be said for patients with high risk (HR) disease. In the last decade multi-modality treatment of HR NBL patients has been intensified to include chemotherapy, surgery, radiation, bone marrow transplantation and immunotherapy and has resulted in improved survival (Yu, 2009). Data regarding the medium to long-term side effects of this intensive multi-modality therapy is now being collected as the population of HR neuroblastoma survivors continues to grow. Methods: We retrospectively reviewed the clinical data of survivors of HR NBL treated at the Children’s Hospital of Illinois diagnosed since 2009 and evaluated the long-term side effects of survivors through 2015. Results: We found 14 NBL patients of whom 10 had HR disease. Four patients died of progressive disease. Therapy-related, long-term side effects occurred in 6 patients: hearing loss (n = 6), adrenal insufficiency (n = 2), focal nodular hyperplasia of the liver (n = 2), linear growth retardation (n = 1). No patient in our cohort developed thyroid or cardiac problems and no patient was diagnosed with a second malignancy in the 5 years of observation. Conclusions: While the improved outcomes seen in HR NBL patients is encouraging, we found in our small cohort hat survivors of multimodality therapy for high-risk neuroblastoma experience significant long-term effects of treatment which impact their quality of life as well as growth and development. As the number of NBL survivors increases our understanding of the long-term therapy related side effects will continue to improve. Larger longitudinal studies are needed to monitor for other possible side effects that may manifest overtime such as cardiomyopathy, disturbances in sexual development, fertility, intellectual function, learning problems and therapy related second malignancies later in life.
Metabolic syndrome in childhood cancer survivors.
Authors: thanga Tamilselvan Santhini , Scott Julius Xavier , Sneha Latha , J Divyalakshmi
Published: March 2017

145

Background: Reavan in 1988 noted that several risk factors for cardiovascular diseases commonly cluster together, and he recognised them as a disease, named syndrome X, currently known as metabolic syndrome. Metabolic syndrome is a group of disorders related to insulin resistance, characterized clinically by central obesity, hyperglycemia, dyslipidemia and hypertension. There is a growing body of evidence indicating that pediatric cancer survivors are at a greater risk of developing metabolic syndrome. We studied the prevalence of metabolic syndrome in children with cancer who completed their treatment and on follow up. Methods: All relevant past medical data (of the disease, treatment and all events) were collected from the medical records. Tanner staging was perfomred, height was measured using a Harpenden stadiometer. Weight/WAIST circumference were measured. The body mass index (BMI) was calculated as weight (kg)/(height (m)²). BMI ≥90thcentile as per CDC chart was taken as abnormal. Blood pressure was measured on the right arm of the patient. Presence of family history of diabetes, cardiovascular diseases and hypercholesterolemia were taken. Fasting Blood sugar, insulin, HbA1C, lipid profile were done. We used IDF(International diabetes federation) criteria to assess the metabolic syndrome among cancer survivors. This study was approved by our university ethics comittee. Results: Seventy five children who fulfilled the inclusion criteria were included in this study. Out of which 48 were males and 27 were females. Among these, majority of children are treated for acute lymphoblastic leukemia. 8.25% of total population satisfied the criteria of metabolic syndrome. Age, gender, diagnosis, modality of treatment were not to be of statistical significance, however majority of children with metabolic syndrome are in adolescent group. Conclusions: With the better care committed to children with cancer even in developing country, the survival rates are greatly improving and so metabolic syndrome is becoming the major target for intervention in the follow up of cancer survivors. As metabolic syndrome cannot treated by a single drug therapy, it is necessary to have cancer survivors follow up screening.
Virtual weight loss program for African-American breast cancer survivors: Preliminary results.
Authors: Ferrante Jeanne M. , Doose Michelle , Bator Alicja , Devine Katie , Ohman Strickland Pamela , Angelino Alessandra , Lee Jennifer , Koransky Alison , Hwang Kevin , Bandera Elisa
Published: March 2017

163

Background: Obesity is associated with higher breast cancer recurrence and death, and poorer health and quality of life. African-American (AA) women have the highest prevalence of obesity, obesity-related comorbidities, and breast cancer mortality compared with other racial/ethnic groups. Weight loss after breast cancer diagnosis may lower rates of recurrence and improve fitness, fatigue, and quality of life. Methods: This 6-month randomized controlled trial pilot-tests the use of a Fitbit activity tracker (Fitbit only group) versus Fitbit plus SparkPeople, a free web-based weight loss program (combined group) among 70 AA breast cancer survivors. Paired t-tests assess changes from baseline to 6-months among each participant in primary (weight, body mass index [BMI], percent body fat) and secondary (24-hour caloric intake, daily number of steps, quality of life, self-monitoring strategies, self-efficacy) outcomes. Two-group t-tests assess differences in outcomes between the two groups. Results: Currently, 36 of 46 (78.3%) eligible participants have enrolled and completed baseline assessments. Mean age of participants is 61.7 years (SD 8.7) and mean BMI is 36.9 (SD 7.0). Analyses of the first 25 participants who completed 3-month assessments (Fitbit only N = 12; combined group N = 13) show significant weight loss in both groups; Fitbit only: mean weight change -6.73 pounds, SD 4.61, p < 0.001; mean BMI change -0.96 kg/m2, SD 0.84, p = 0.002; combined group: mean weight change -5.95 pounds, SD 5.84, p = 0.003; mean BMI change -1.03 kg/m2, SD 0.77, p < 0.001. All participants significantly increased tracking of diet (Fitbit only p = 0.016; combined group p < 0.001) and physical activity (Fitbit only p < 0.001; combined group p = 0.001). Though not significant, combined group participants showed greater increases in self-efficacy for eating healthy and reducing fat and calories, and increases in daily steps (+1308 vs. +285 for Fitbit only group). Preliminary analyses show no statistically significant difference in changes in outcomes from baseline to 3 months between the two groups. Conclusions: Both programs show potential as convenient and efficient weight loss methods for African-American breast cancer survivors. Clinical trial information: NCT02699983.
Exercise, metabolic syndrome, and cardiovascular fitness in breast cancer survivors.
Authors: Knobf M. Tish , Sinusas Albert , Holland Margaret , Jeon Sangchoon
Published: March 2017

165

Background: Metabolic syndrome (MetS) has been reported higher in breast cancer survivors (BCS) compared to age-matched postmenopausal women. The risk for cardiovascular disease and diabetes is significantly increased in women with MetS. Lifestyle behaviors are recommended first line interventions to reduce risk for MetS. Methods: From a 12 month randomized controlled trial (RCT) of a fitness center exercise intervention compared to a home physical activity group, the criteria for MetS (3 of 5 components: waist circumference [WC] ≥ 80cm, triglycerides ≥ 150mg/dL, HDL cholesterol < 40 mg/dL, blood pressure [BP] ≥ 130/85 mmHg, fasting blood sugar [FBS] > 100mg/dL) were used to identify BCS with MetS. General estimating equation was employed for longitudinal changes. Heart rate recovery (reduction in heart rate from peak heart rate at one minute after exercise stress test) was used as a measure of cardiovascular fitness. Pearson correlation coefficients assessed associations between heart rate recovery and metabolic outcomes. Results: Of 148 subjects in the RCT, 21.6% (N = 32) met the criteria for MetS, with a higher baseline incidence in the home (30.1%) versus fitness center (13.3%) groups (p = 0.01). Of subjects on Tamoxifen, 30.9% had MetS, compared to 17.1% on an aromatase inhibitor and 20.7% not on endocrine therapy; these were not significantly different (p = .28). Among those with MetS at baseline, we observed a significant decrease in MetS (p < .01) with significant changes in HDL (p = 0.02) and FBS (p = .01) after the 12 month intervention. The fitness center and home physical activity groups both resulted in fewer subjects meeting MetS criteria at 12 months, but only the home group had a significant change over time (OR = 0.66 (0.44, 0.98) p = .04). Heart recovery rate at 6 months was significantly associated with all 5 MetS components: WC (-0.28 p < .01), triglycerides (-0.32 p < .01), HDL (0.20 p = .04), systolic BP (-0.38 p < .01), diastolic BP (-0.27 p < .01) and FBS (-0.35 p < .01). Conclusions: All-cause mortality now exceeds breast cancer specific mortality. MetS identifies a unique vulnerable population of BCS at high risk for cardiovascular disease. Lifestyle behaviors represent critical risk reduction strategies.
Development and pilot test of a dyadic psychosocial intervention for couples coping with head and neck cancer.
Authors: Badr Hoda
Published: March 2017

187

Background: Patients receiving radiotherapy for head and neck cancers (HNCs) experience significant persistent side effects such as abnormally reduced salivation, difficulty swallowing, and taste changes. To control these side effects and minimize discomfort, intensive self-care protocols are prescribed, but adherence is poor. Spouses/partners play a critical role in supporting adherence, but often lack knowledge, experience high rates of distress, and display poor communication that can interfere with patient self-management and self-care. Methods: We developed and pilot-tested a skills-training intervention comprised of tailored manuals and 6 counseling sessions delivered over the telephone to HNC patients and their partners. The goal is to reduce healthcare utilization and improve patient and partner quality of life (QOL). To guide the development and content of the intervention, qualitative interviews with 6 HNC patients (83% male) and 6 spouses were analyzed using a grounded theory approach. For the pilot test, couples completed surveys prior to initiating radiotherapy and were randomized to the intervention or usual medical care. Eight weeks later, they completed follow-up surveys. Results: Based on the qualitative findings, we developed the intervention to teach: 1) self-management skills; 2) communication skills; and 3) strategies to improve communal coping and confidence in the ability to work as a team. To date, 20 couples (Mean Age = 57 years; SD = 8) have participated. Solid recruitment (83%) and low attrition rates demonstrate feasibility. Strong program evaluations (Mean = 8.7 out of 10) and homework completion rates (85%) support acceptability. Conclusions: This is the first program in HNC that actively involves both members of the couple to address barriers in the home environment in which self-management occurs. By empowering couples with the skills to coordinate care and support, the program holds great promise for improving self-management behaviors, reducing costly hospitalizations and treatment interruptions, and improving patient and partner QOL.
Evaluation of the psychosocial needs of cancer survivors.
Authors: Pabbathi Smitha , Abid Ariana , Mehta Kanan , Martinez Dinorah Tyson , Hall Carrie , McMillan Susan
Published: March 2017

207

Background: Even after enduring successful treatment of their cancer, the late physical and psychosocial effects of treatment often continue to haunt as many as 50% of survivors. Furthermore, the needs of cancer survivors differ from those undergoing active treatment. However, there is a lack of comprehensive assessment for providers caring for survivors. Therefore, there is a need for one tool to assess the physical and psychosocial needs as well as evaluate their severity when initially establishing care in general survivorship clinic. In this study, we determine the most commonly identified of these needs as well as the degree to which they impact overall health of this population. Methods: A retrospective chart review of 220 patient records from the past six years in General Survivorship Clinic using Moffitt Cancer Center’s EHR was performed. All patients (ages 18-85 years) diagnosed with cancer without evidence of current disease and who had complete Clinical Needs Assessment Tool for Cancer Survivors (CNAT-CS) were eligible for inclusion. The CNAT- CS is a questionnaire of 36 items on which survivors identify as “not a concern”, “is a concern but I am managing”, or “I need help”. Results: A majority (65.5%) was female and white (81.3%); African Americans made up 11.4%. The mean age was 57.6 (SD = 11.3). Subjects had survived a variety of types of cancer with more than half (57%) having breast cancer. Their mean distress score was 2.75 (SD = 2.86). Fear of recurrence was the concern most often identified (56%), followed by feeling of high stress (50%), sleep disturbances (49%) and memory/ attention difficulties (40%). Highest scores were found on items about fear of the cancer returning (Mean = 0.71; SD = .55), information needed for follow-up care (mean = .64; SD = .59), stress in my life (mean = .60; SD = .65) and trouble with my memory/attention (mean = 0.52; SD = .69). Conclusions: These results indicate a relatively low mean distress score from the distress thermometer. Areas identified most frequently as a concern also tended to be the areas with the highest mean scores. Although almost 20% of survivors were in minority groups, ethnic minorities were underrepresented in this sample. Thus, future studies should focus on increasing the representativeness of the sample.
Perceptions and consequences of cancer-related weight loss among patients with cancer and caregivers.
Authors: Buzaglo Joanne S , Zaleta Alexandra K , Miller Kayla M , Kennedy Victoria , Charap Ellyn Specker
Published: March 2017

224

Background: Cancer-related weight loss affects up to 50% of individuals with cancer, yet our understanding of psychosocial consequences of this weight loss is limited. This study examined patient and caregiver perceptions of symptoms and consequences of cancer-related weight loss. Methods: Patients with self-reported weight loss (n = 15; 26% non-mBC, 13% colorectal, 13% MM, 13% ovarian, 35% other; mean BMI = 22.9) and caregivers of people experiencing weight loss (n = 15) were recruited through the online Cancer Experience Registry. Participants completed a one-hour phone interview about views about weight loss; transcribed responses underwent content and thematic analysis by three coders (agreement = 89%). Results: Across participants, the most commonly reported weight loss-related symptoms included appetite changes (80% of participants), nausea (73%), and taste changes (60%). Most bothersome consequences of weight loss for patients included fear of disease progression (53%), loss of identity (47%), caregiver burden worries (40%), anxiety (27%), and body image concerns/embarrassment about physical appearance (27%). Most bothersome consequences for caregivers were burden of providing care (80%), distress about physical appearance of the patient (80%), changed sense of patient identity (60%), fear of illness progression (53%), and family impact (40%). Weight loss acceptance varied by BMI; obese/overweight patients reported greater acceptance, citing improvements in body image and better physical fitness as reasons for acceptance. Only 33% of patients and 22% of caregivers reported that their healthcare team addressed cancer-related weight loss during medical visits. Conclusions: With respect to cancer-related weight loss, patients and caregivers most often identified psychosocial concerns as bothersome; concerns about weight loss causing changes in physical appearance were more prevalent among caregivers. These results support development of a psychometric measure to evaluate cancer-related weight loss and suggest the need for better integration of cancer-related weight loss concerns into survivorship care plans.
Systemic Lupus Erythematosus Is Associated With Increased Adverse Postoperative Renal Outcomes and Mortality: A Historical Cohort Study Using Administrative Health Data
Authors: Babazade Rovnat , Yilmaz Huseyin Oguz , Leung Steve M. , Zimmerman Nicole M. , Turan Alparslan
Published: March 2017

BACKGROUND:

Systemic lupus erythematosus (SLE) is a common autoimmune connective tissue disease that mainly harms kidneys, heart, lungs, and nervous system. Effects of surgical stimulus and anesthesia combined with SLE-related pathologies may increase morbidity and mortality. Therefore, we aimed to evaluate the association between SLE (versus none) and postoperative renal, cardiac, and in-hospital mortality complications among patients undergoing major surgeries.

METHODS:

We obtained censuses of 2009 to 2011 inpatient hospital discharges across 7 states and conducted a retrospective cohort study by using International Classification of Diseases and Injuries, Version 9, diagnosis codes, procedure codes, and present-on-admission indicators. We included patients who had major surgery and matched each SLE discharge up to 4 control discharges for potential confounders. We assessed the association between matched SLE patients and controls on in-hospital renal complications, cardiovascular complications, and in-hospital mortality using separate logistic regression models.

RESULTS:

Among 8 million qualifying discharges, our sample contained 28,269 SLE patients matched with 13,269 controls. SLE was associated with a significantly higher risk of postoperative renal complications, with an estimated odds ratio (99% CI) of 1.33 (1.21, 1.46);P< .001. In addition, SLE was significantly associated with a higher risk of in-hospital mortality, with an estimated odds ratio (99% CI) of 1.27 (1.11, 1.47);P< .001. However, we found no significant association between SLE and cardiac complications, with an estimated odds ratio (99% CI) of 0.98 (0.83, 1.16),P= .79.

CONCLUSIONS:

This is, by far, the largest clinical study for postoperative outcomes of SLE patients with adequately powered statistical analyses. We concluded that SLE was associated with a higher risk of renal complications and in-hospital mortality but not cardiac events after major surgery. In SLE patients, more aggressive measures should be taken to prevent renal injury in the perioperative period.
Continuous Transversus Abdominis Plane Nerve Blocks: Does Varying Local Anesthetic Delivery Method—Automatic Repeated Bolus Versus Continuous Basal Infusion—Influence the Extent of Sensation to Cold?: A Randomized, Triple-Masked, Crossover Study in Volunteers
Authors: Khatibi Bahareh , Said Engy T. , Sztain Jacklynn F. , Monahan Amanda M. , Gabriel Rodney A. , Furnish Timothy J. , Tran Johnathan T. , Donohue Michael C. , Ilfeld Brian M.
Published: March 2017

BACKGROUND:

It remains unknown whether continuous or scheduled intermittent bolus local anesthetic administration is preferable for transversus abdominis plane (TAP) catheters. We therefore tested the hypothesis that when using TAP catheters, providing local anesthetic in repeated bolus doses increases the cephalad-caudad cutaneous effects compared with a basal-only infusion.

METHODS:

Bilateral TAP catheters (posterior approach) were inserted in 24 healthy volunteers followed by ropivacaine 2 mg/mL administration for a total of 6 hours. The right side was randomly assigned to either a basal infusion (8 mL/h) or bolus doses (24 mL administered every 3 hours for a total of 2 bolus doses) in a double-masked manner. The left side received the alternate treatment. The primary end point was the extent of sensory deficit as measured by cool roller along the axillary line at hour 6 (6 hours after the local anesthetic administration was initiated). Secondary end points included the extent of sensory deficit as measured by cool roller and Von Frey filaments along the axillary line and along a transverse line at the level of the anterior superior iliac spine at hours 0 to 6.

RESULTS:

Although there were statistically significant differences between treatments within the earlier part of the administration period, by hour 6 the difference in extent of sensory deficit to cold failed to reach statistical significance along the axillary line (mean = 0.9 cm; SD = 6.8; 95% confidence interval –2.0 to 3.8; P = .515) and transverse line (mean = 2.5 cm; SD = 10.1; 95% confidence interval –1.8 to 6.8; P = .244). Although the difference between treatments was statistically significant at various early time points for the horizontal, vertical, and estimated area measurements of both cold and mechanical pressure sensory deficits, no comparison remained statistically significant by hour 6.

CONCLUSIONS:

No evidence was found in this study involving healthy volunteers to support the hypothesis that changing the local anesthetic administration technique (continuous basal versus hourly bolus) when using ropivacaine 0.2% and TAP catheters at 8 mL/h and 24 mL every 3 hours significantly influences the cutaneous effects after 6 hours of administration. Additional research is required to determine whether changing variables (eg, local anesthetic concentration, basal infusion rate, bolus dose volume, and/or interval) would provide different results.
Writing the Lives of Saints
Authors: Curtis Sarah A.
Published: March 2017

This article discusses the difficulty of access to the archives of women's religious orders in France based on the author's experiences and research. It argues that the reluctance that these orders often show in allowing outside researchers access to their records results from four overlapping and interlocking contexts: the impact of French culture wars during the Third Republic, the role of gender, the canonization policies of John Paul II, and the self-identification of religious orders as families whose history must remain private. Taken together, they strike at the heart of issues of trust, identity creation and reinforcement, and the relationship between private and public in the past and in the present. The purpose of this article is to reflect on the encounter between sister archivists and lay researchers as a way of thinking about archival practice and also of interrogating how the history of women religious has been conceptualized and studied.

Cet article examine les problèmes d'accès aux archives des congrégations religieuses féminines à partir de l'expérience et des recherches de l'auteur. Il constate que la réticence que montrent souvent ces congrégations auprès des chercheurs non-congréganistes s'ensuit de quatre contextes liés : les conséquences des conflits entre l'Etat et l'Eglise pendant la Troisième République ; les rôles des sexes ; la politique de canonisation de Jean-Paul II ; et l'auto-identification des congrégations comme des familles pour lesquelles l'histoire doit rester privée. Ensemble, ces contextes vont au cœur des questions de la confiance, de la création et du renforcement des identités, et des rapports historiques et contemporains entre les sphères privée et publique. L'objectif de cet article est de réfléchir sur la rencontre entre les sœurs-archivistes et les chercheurs laïcs pour penser le problème des archives et aussi pour interroger la manière dont l'histoire des religieuses a été conçue et étudiée.
Regulation of DNA replication and chromosomal polyploidy by the MLL-WDR5-RBBP5 methyltransferases
Authors: Lu Fei , Wu Xiaojun , Yin Feng , Chia-Fang Lee Christina , Yu Min , Mihaylov Ivailo S. , Yu Jiekai , Sun Hong , Zhang Hui
Published: March 2017

DNA replication licensing occurs on chromatin, but how the chromatin template is regulated for replication remains mostly unclear. Here, we have analyzed the requirement of histone methyltransferases for a specific type of replication: the DNA re-replication induced by the downregulation of either Geminin, an inhibitor of replication licensing protein CDT1, or the CRL4CDT2 ubiquitin E3 ligase. We found that siRNA-mediated reduction of essential components of the MLL-WDR5-RBBP5 methyltransferase complexes including WDR5 or RBBP5, which transfer methyl groups to histone H3 at K4 (H3K4), suppressed DNA re-replication and chromosomal polyploidy. Reduction of WDR5/RBBP5 also prevented the activation of H2AX checkpoint caused by re-replication, but not by ultraviolet or X-ray irradiation; and the components of MLL complexes co-localized with the origin recognition complex (ORC) and MCM2-7 replicative helicase complexes at replication origins to control the levels of methylated H3K4. Downregulation of WDR5 or RBBP5 reduced the methylated H3K4 and suppressed the recruitment of MCM2-7 complexes onto replication origins. Our studies indicate that the MLL complexes and H3K4 methylation are required for DNA replication but not for DNA damage repair.
Walking economy at simulated high altitude in human healthy young male lowlanders
Authors: Horiuchi Masahiro , Handa Yoko , Abe Daijiro , Fukuoka Yoshiyuki
Published: March 2017

We measured oxygen consumption during walking per unit distance (Cw) values for 12 human healthy young males at six speeds from 0.667 to 1.639 m s−1 (four min per stage) on a level gradient under normobaric normoxia, moderate hypoxia (15% O2), and severe hypoxia (11% O2). Muscle deoxygenation (HHb) was measured at the vastus lateralis muscle using near-infrared spectroscopy. Economical speed which can minimize the Cw in each individual was calculated from a U-shaped relationship. We found a significantly slower economical speed (ES) under severe hypoxia [1.237 (0.056) m s−1; mean (s.d.)] compared to normoxia [1.334 (0.070) m s−1] and moderate hypoxia [1.314 (0.070) m s−1, P<0.05 respectively] with no differences between normoxia and moderate hypoxia (P>0.05). HHb gradually increased with increasing speed under severe hypoxia, while it did not increase under normoxia and moderate hypoxia. Changes in HHb between standing baseline and the final minute at faster gait speeds were significantly related to individual ES (r=0.393 at 1.250 m s−1, r=0.376 at 1.444 m s−1, and r=0.409 at 1.639 m s−1, P<0.05, respectively). These results suggested that acute severe hypoxia slowed ES by ∼8%, but moderate hypoxia left ES unchanged.
Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy
Authors: Ghazi Lama , Drawz Paul
Published: March 2017

The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the physiology of blood pressure control and the pathophysiology of hypertension (HTN) with effects on vascular tone, sodium retention, oxidative stress, fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents have been available to treat HTN since the 1970s and newer medications are being developed. In this review, we will (1) examine new anti-hypertensive medications affecting the RAAS, (2) evaluate recent studies that help provide a better understanding of which patients may be more likely to benefit from RAAS blockade, and (3) review three recent pivotal randomized trials that involve newer RAAS blocking agents and inform clinical practice.
The Time Window Assignment Vehicle Routing Problem with Time-Dependent Travel Times
Authors: Spliet Remy , Dabia Said , Van Woensel Tom
Published: March 2017

In this paper, we introduce the time window assignment vehicle routing problem (TWAVRP) with time-dependent travel times. It is the problem of assigning time windows to customers before their demand is known and creating vehicle routes adhering to these time windows after demand becomes known. The goal is to assign the time windows in such a way that the expected transportation costs are minimized. We develop a branch-price-and-cut algorithm to solve this problem to optimality. The pricing problem that has to be solved is a new variant of the shortest path problem, which includes a capacity constraint, time-dependent travel times, time window constraints on both the nodes and on the arcs, and linear node costs. For solving the pricing problem, we develop an exact labeling algorithm and a tabu search heuristic. Furthermore, we present new valid inequalities, which are specifically designed for the TWAVRP with time-dependent travel times. Finally, we present results of numerical experiments to illustrate the performance of the algorithm.
Self-harm among ostomates: confronting a hidden issue
Authors: Bird Andrew
Published: March 2017

Andrew Bird, Stoma Care Nurse Specialist, Nottingham University Hospitals, looks at self-harm among people with a stoma, offering advice on identifying the triggers and signs of this behaviour, as well as strategies for how to be prepared to help
The prevalence of psychological problems among ostomy patients: a cross-sectional study from Iran
Authors: Rafiei Hossein , Hoseinabadi-Farahani Mohammad Javad , Aghaei Sedigheh , Hosseinzadeh Kazem , Naseh Ladan , Heidari Mohammad
Published: March 2017

Background and aims:

Patients with chronic conditions often develop psychiatric disorders, most commonly depression, stress and anxiety, which may worsen the disease. This study examines the prevalence of depression, stress and anxiety among ostomy patients.

Methods:

A descriptive cross-sectional study was carried out, with participants selected using convenience sampling from all those who presented for follow up for routine stoma care in a wound clinic in Isfahan, Iran. Data were collected using a demographic variables checklist and the Depression, Anxiety, Stress Scale 21 (DASS-21).

Results:

Of the 70 participants, 51% were women and the rest were men. The mean age was 62.6 ± 14.1 years (range: 32–91 years). The mean scores for depression, anxiety and stress were 10.9 ± 5.4, 13.1±4.8 and 10.6 ± 5.8 respectively. In total, some level of depression, anxiety and stress was reported by 87%, 92.1% and 71% of patients respectively. Factors such as patients' sex, age, type of stoma and duration of living with stoma appeared to affect patients' levels of depression, anxiety and stress.

Conclusion:

The rate of psychological problems among ostomy patients is high. Health-care providers should be aware of this and plan for prevention. Further study in this regard is strongly recommended.