tbuckley/cabot-search huggingface dataset:
Physiological and psychosocial effects of a highly structured exercise program on breast cancer survivorship.
Authors: Judy A. Tjoe, Linda B. Piacentine, Jun Yin, Paula Papanek, Alexander V. Ng
Journal: Journal of Clinical Oncology (2019)

11558 Background: Exercise after breast cancer treatment improves cancer-related outcomes, although the mechanism of action is unclear. Engagement in healthy active lifestyles after cancer treatment may also impact overall survival. We aimed to determine effectiveness of a highly structured, clinically overseen, goal oriented, group triathlon training program on improving physiological and psychosocial outcomes in female breast cancer survivors (BCS). Methods: After stage appropriate local and systemic breast cancer treatment, 53 female BCS were recruited to participate in this study. The 14-week group triathlon training program was individually adjusted for treatment side effects. 28 similar BCS who did not participate in the training served as controls. Pre- and post-exercise training measures included: Functional endurance (Timed 6MWT), quality of life (QOL, FACT-B), cancer-related fatigue (CRF, FACIT-F), exercise self-efficacy (ESE) via questionnaires, estradiol, and inflammatory biomarkers (C-reactive protein, TNFr1, leptin and adiponectin). Results: Complete data were obtained from 41 [mean age 51 (7) yr, mean BMI 29.5 (6.2)] triathlon finishers and 16 [mean age 56 (10) yr, mean BMI 31.5 (8.0)] controls. 6MWT improved (26 m) more in the triathlon group (p &lt; 0.05). FACT-B, FACIT-F, and ESE all improved compared to controls (all p &lt; 0.05). Body mass and BMI decreased in the training group compared to controls (p = 0.01, p = 0.04 respectively). Arm circumference decreased in the trained group but increased in controls (p &lt; 0.05). Estradiol and leptin positively correlated with initial body weight in both groups but did not change after training. Adiponectin significantly decreased in the triathlon group (p = 0.01), perhaps due to selection bias of controls. No significant changes were seen in other serological markers. Conclusions: A highly structured, clinically overseen, moderate intensity exercise program can improve endurance, QOL, CRF, body mass, and possibly improve survival after breast cancer treatment. Furthermore, improvements in ESE may provide tools for patients to continue adherence to regular exercise guidelines that may lower obesity and its related comorbidities, including arm lymphedema.
10 minute consultation: Newly diagnosed type 2 diabetes mellitus
Authors: Susan M Smith
Journal: BMJ (2003)

A 62 year old woman has returned to you for the results of blood tests. She had attended for a well woman check up two weeks earlier and had mentioned that she was experiencing persistent fatigue. A random plasma glucose test that day showed a glucose concentration of 11.4 mmol/l, so you had arranged for her to have a fasting blood glucose test. Her fasting blood glucose was 8.5 mmol/l. She has no history of vascular disease or other serious medical conditions. Her aunt had diet controlled diabetes and died of a cerebrovascular event at the age of 68.​68.



Figure 1

Initial management of newly diagnosed type 2 diabetes
Tumor mutation burden and depression in lung cancer: Association with inflammation.
Authors: Daniel Curtis McFarland, Devika R Jutagir, Barry Rosenfeld, Andrew H. Miller, Christian J. Nelson, William Breitbart
Journal: Journal of Clinical Oncology (2019)

e23159 Background: Depression and inflammation are both associated with lung cancer. Tumor Mutation Burden (TMB) can be used to predict immunotherapy response which relies on tumor immunogenicity, a form of inflammation. This study evaluated whether higher TMB was associated with increased depression and various forms of inflammation. Methods: Patients with metastatic Non-small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) receiving anticancer treatments were evaluated for depression severity using the Hospital Anxiety and Depression Scale (HADS). TMB was measured using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). Inflammation was evaluated using C - reactive protein (CRP) and the Neutrophil to Lymphocyte Ratio (NLR). Results: Ninety-six out of 140 participants with adequate TMB testing were evaluated (68.6%). The average number of mutations was 10.8 (SD 10.8). Twenty-four percent met screening criteria for depression. TMB correlated with depression severity (r = .34, p = .001) and NLR (r = .37, p = .002) and absolute neutrophil count (r = .3, p = .006) but not CRP (r = .193, p = .06). TMB was higher in patients receiving chemotherapy (12.0) and immunotherapy (14.4) over targeted therapy (4.8). A multivariate model found that TMB (β = .25, p = .032) and CRP (β = .36, p = .003) predicted for depression severity. Conclusions: TMB is an independent predictor of depression. Inflammatory indices suggest a possible relationship but the exact mechanism should be further evaluated and the results warrant replication. Ultimately, these findings may help identify lung cancer patients at risk for depression. [Table: see text]
Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer
Authors: Panagiotis A. Konstantinopoulos, Weixiu Luo, Joyce F. Liu, Doga C. Gulhan, Carolyn Krasner, Jeffrey J. Ishizuka, Allison A. Gockley, Mary Buss, Whitfield B. Growdon, Heather Crowe, Susana Campos, Neal I. Lindeman, Sarah Hill, Elizabeth Stover, Susan Schumer, Alexi A. Wright, Jennifer Curtis, Roxanne Quinn, Christin Whalen, Kathryn P. Gray, Richard T. Penson, Stephen A. Cannistra, Gini F. Fleming, Ursula A. Matulonis
Journal: Journal of Clinical Oncology (2019)

Despite the tissue-agnostic approval of pembrolizumab in mismatch repair deficient (MMRD) solid tumors, important unanswered questions remain about the role of immune checkpoint blockade in mismatch repair-proficient (MMRP) and -deficient endometrial cancer (EC).This phase II study evaluated the PD-L1 inhibitor avelumab in two cohorts of patients with EC: (1) MMRD/POLE (polymerase ε) cohort, as defined by immunohistochemical (IHC) loss of expression of one or more mismatch repair (MMR) proteins and/or documented mutation in the exonuclease domain of POLE; and (2) MMRP cohort with normal IHC expression of all MMR proteins. Coprimary end points were objective response (OR) and progression-free survival at 6 months (PFS6). Avelumab 10 mg/kg intravenously was administered every 2 weeks until progression or unacceptable toxicity.Thirty-three patients were enrolled. No patient with POLE-mutated tumor was enrolled in the MMRD cohort, and all MMRP tumors were not POLE-mutated. The MMRP cohort was closed at the first stage because of futility: Only one of 16 patients exhibited both OR and PFS6 responses. The MMRD cohort met the predefined primary end point of four ORs after accrual of only 17 patients; of 15 patients who initiated avelumab, four exhibited OR (one complete response, three partial responses; OR rate, 26.7%; 95% CI, 7.8% to 55.1%) and six (including all four ORs) PFS6 responses (PFS6, 40.0%; 95% CI, 16.3% to 66.7%), four of which are ongoing as of data cutoff date. Responses were observed in the absence of PD-L1 expression. IHC captured all cases of MMRD subsequently determined by polymerase chain reaction or genomically via targeted sequencing.Avelumab exhibited promising activity in MMRD EC regardless of PD-L1 status. IHC for MMR assessment is a useful tool for patient selection. The activity of avelumab in MMRP/non-POLE-mutated ECs was low.
Urinary incontinence in women with gynecologic malignancies before and after primary therapy
Authors: L. S. Downs, Z. Li, J. F. Wyman
Journal: Journal of Clinical Oncology (2007)

9087 Background: There is limited data on the impact of treatment for gynecologic cancer on future urinary incontinence. Our objective is to determine degree of urinary incontinence in women previously treated for gynecologic cancer and women not yet treated. Methods: With IRB approval gynecologic cancer patients that had completed therapy over 1 year prior and those not yet receiving therapy were asked to participate. Consenting subjects completed the Incontinence Impact Questionnaire (IIQ) and Urogenital Distress Inventory (UDI). Both are scored from 0–100 with higher scores representing more incontinence. We also assessed general health. Mean scores were calculated and compared with adjustments for covariates. In established patients Kruskal-Wallis was used to test overall equality of IIQ and UDI across various diagnoses and treatments. Results: Ninety new patients and 104 established patients were enrolled. Age, parity, tobacco use and use of incontinence medications were similar between the groups. General health status was worse in the new patients (p&lt;0.0001). Mean (± S.E.) IIQ scores were similar between new (6.87 ± 1.4) and established patients (4.76 ± 0.96), p=0.56. Mean UDI scores were also similar for new (17.2 ± 9.0) and established (13.2 ± 9.8) patients, p=0.20. After adjusting for health status, parity, age, tobacco use, prior use of incontinence medications there was no significant difference in either score. There was a significant positive association between age and incontinence as assessed by IIQ (p=0.02). We compared scores for established patients diagnosed with cervical, ovarian, uterine and vulvar cancer and found no significant difference in either IIQ (p=0.55) or UDI (p=0.76). Similarly there was no significant difference in scores for patients receiving hysterectomy, radical hysterectomy, BSO, vulvectomy, tumor debulking, chemotherapy or radiation therapy. Although not significant there was a trend toward more incontinence in patients having received radical hysterectomy. Conclusions: Urinary incontinence as measured by IIQ and UDI dose not appear to be different at the time of diagnosis of gynecologic cancer and a year from the completion of therapy. There is no apparent difference in urinary incontinence across diagnoses. No significant financial relationships to disclose.
Diseases of the Heart and Aorta.
Journal: JAMA (1906)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Clinical outcome of patients managed for late relapse of germ cell tumor
Authors: D. S. Sharp, B. S. Carver, S. E. Eggener, G. V. Kondagunta, R. J. Motzer, G. J. Bosl, J. Sheinfeld
Journal: Journal of Clinical Oncology (2006)

4550 Background: The significance of late relapse (LR) of germ cell tumor (GCT) and its association with poor survival is becoming increasingly recognized. Methods: Between 1990 and 2004, 75 patients (pts) were managed for LR of GCT at MSKCC. Using our prospective databases and following IRB approval, clinical and pathologic parameters were reviewed. Estimates of cancer-specific survival were generated using the Kaplan-Meier method and Cox-proportional hazards model was used to assess for predictors of outcome. Results: Clinical stage (CS) at initial presentation was I in 15 (21%), II in 32 (44%), and III in 26 (36%) of pts. Management prior to LR included surveillance in 10 (13%) pts, RPLND only in 8 (11%) pts, chemotherapy only in 19 (25%) pts, and both chemotherapy (induction or adjuvant) and RPLND in 38 (51%) pts. The median time to LR was 6.8 (2.1–37.7) years. Overall, 56/75 (75%) of pts had LR in the retroperitoneum (RP), including 25 of 27 (93%) initially managed without RPLND prior to LR. At LR, 45/75 (60%) of pts were symptomatic and 46/75 (61%) pts had elevated serum tumor markers (STM) (78% AFP and 39% βHCG). Overall 5 year cancer-specific survival (CSS) was 59% (95% CI 47%–72%). Pts who underwent complete resection (with or without salvage chemotherapy) at time of LR (n = 44) had a 5 year CSS of 77% (95% CI 62%–92%). In contrast, 5 year CSS for patients treated without complete surgical resection (n = 31) was 39% (95% CI 21%–57%) (p = 0.0001). The pathology of 69 pts at LR revealed viable GCT in 39 (57%), only teratoma in 13 (19%), malignant transformation in 14 (20%), and fibrosis in 3 (4%). A multivariable analysis of pretreatment parameters showed that at time of LR, a solitary site of metastasis (HR 2.6, 95% CI 1.1–6.2, p = 0.03) and no prior chemotherapy (HR 4.2, 95% CI 1.2–14.2, p = 0.02) were predictive of improved cancer-specific survival. Elevated STM and presence of symptoms did not impact survival independently in this model. Conclusions: Although LR of GCT is associated with poor survival, pts who are chemotherapy naïve and have a solitary metastatic site at LR experience improved survival. The data suggest that meticulous control of the RP is critical to prevent LR in the RP. Survival is greatly improved if complete surgical excision of disease at LR is attained, highlighting the critical role for surgery in these patients. No significant financial relationships to disclose.
Polymorphism Data Assist Estimation of the Nonsynonymous over Synonymous Fixation Rate Ratio ω for Closely Related Species
Authors: Carina F Mugal, Verena E Kutschera, Fidel Botero-Castro, Jochen B W Wolf, Ingemar Kaj
Journal: Molecular Biology and Evolution (2019)

Abstract The ratio of nonsynonymous over synonymous sequence divergence, dN/dS, is a widely used estimate of the nonsynonymous over synonymous fixation rate ratio ω, which measures the extent to which natural selection modulates protein sequence evolution. Its computation is based on a phylogenetic approach and computes sequence divergence of protein-coding DNA between species, traditionally using a single representative DNA sequence per species. This approach ignores the presence of polymorphisms and relies on the indirect assumption that new mutations fix instantaneously, an assumption which is generally violated and reasonable only for distantly related species. The violation of the underlying assumption leads to a time-dependence of sequence divergence, and biased estimates of ω in particular for closely related species, where the contribution of ancestral and lineage-specific polymorphisms to sequence divergence is substantial. We here use a time-dependent Poisson random field model to derive an analytical expression of dN/dS as a function of divergence time and sample size. We then extend our framework to the estimation of the proportion of adaptive protein evolution α. This mathematical treatment enables us to show that the joint usage of polymorphism and divergence data can assist the inference of selection for closely related species. Moreover, our analytical results provide the basis for a protocol for the estimation of ω and α for closely related species. We illustrate the performance of this protocol by studying a population data set of four corvid species, which involves the estimation of ω and α at different time-scales and for several choices of sample sizes.
Longitudinal diffusion tensor magnetic resonance imaging analysis at the cohort level reveals disturbed cortical and callosal microstructure with spared corticospinal tract in the TDP-43G298S ALS mouse model
Authors: Hans-Peter Müller, David Brenner, Francesco Roselli, Diana Wiesner, Alireza Abaei, Martin Gorges, Karin M. Danzer, Albert C. Ludolph, William Tsao, Philip C. Wong, Volker Rasche, Jochen H. Weishaupt, Jan Kassubek
Journal: Translational Neurodegeneration (2019)

In vivo diffusion tensor imaging (DTI) of the mouse brain was used to identify TDP-43 associated alterations in a mouse model for amyotrophic lateral sclerosis (ALS).Ten mice with TDP-43G298S overexpression under control of the Thy1.2 promoter and 10 wild type (wt) underwent longitudinal DTI scans at 11.7 T, including one baseline and one follow-up scan with an interval of about 5 months. Whole brain-based spatial statistics (WBSS) of DTI-based parameter maps was used to identify longitudinal alterations of TDP-43G298S mice compared to wt at the cohort level. Results were supplemented by tractwise fractional anisotropy statistics (TFAS) and histological evaluation of motor cortex for signs of neuronal loss.Alterations at the cohort level in TDP-43G298S mice were observed cross-sectionally and longitudinally in motor areas M1/M2 and in transcallosal fibers but not in the corticospinal tract. Neuronal loss in layer V of motor cortex was detected in TDP-43G298S at the later (but not at the earlier) timepoint compared to wt.DTI mapping of TDP-43G298S mice demonstrated progression in motor areas M1/M2. WBSS and TFAS are useful techniques to localize TDP-43G298S associated alterations over time in this ALS mouse model, as a biological marker.
Relationship between time to onset of relief and total pain relief of breakthrough pain in patients with cancer using fentanyl pectin nasal spray.
Authors: John D. Conroy, Luis M. Torres, Julia Revnic, Ravi Tayi, Michael Sidney Perelman, Alastair D. Knight
Journal: Journal of Clinical Oncology (2012)

e19544 Background: Breakthrough pain in cancer (BTPc) is typified by a rapid onset of severe pain with a limited duration. Treatment for BTPc requires rapid onset of pain relief. The main purpose of this analysis was to assess the relationship between time to onset of pain relief and overall pain relief in patients treating BTPc with fentanyl pectin nasal spray (FPNS, Lazanda, PecFent). Methods: Data were pooled from FPNS-treated episodes of 2 randomized, double-blind, crossover studies assessing efficacy of FPNS in adults who experienced BTPc despite background pain that was adequately controlled with at least 60 mg/day morphine (or equivalent). Patients initially entered a dose-titration phase to establish dose of FPNS (100 to 800 mcg) to be used during the treatment phase of each study. Pain intensity (PI) was assessed at baseline and scheduled time points on an 11-point scale (0=no pain, 10=worst possible pain). This analysis assessed the relationship of time to onset of pain relief (≥1 point reduction in PI from baseline) to total pain relief (Summed Pain Intensity Difference [SPID] at 30 and 60 min postdose [SPID30 and SPID60]) by ANOVA. Responses are also provided for the placebo-treated episodes during the placebo-controlled trial. Results: There were 831 episodes of BTPc that were treated with FPNS. Mean SPID was highest when pain relief was earliest (p&lt;0.001). When PI difference (PID) ≥1 was attained by 5, 10, and 15 min postdose, mean (SD) SPID30 scores were 13.1 (6.7), 7.6 (4.0), and 3.5 (1.8). In the placebo-controlled trial, a similar overall response (p&lt;0.001) was observed during the 200 placebo-treated episodes: among those attaining PID ≥1 by 5, 10, and 15 min postdose, SPID30 was 12.2 (7.0), 5.3 (3.3), and 2.5 (1.0), respectively. Similarly, significant differences were observed for SPID60 with both treatments. Conclusions: Earlier time to onset of pain intensity reduction in BTPc treatment resulted in higher SPID at 30 and 60 minutes postdose of FPNS and placebo. Results suggest that early onset of relief may be associated with a greater overall degree of relief for episodes of BTPc, which emphasizes the need for rapid-acting agents in the management of breakthrough pain.
Characteristics and Outcome of Multiple Myeloma Patients Presenting with Anemia Only: a Retrospective Multi-Center Study
Authors: Tamir Shragai, Moshe E. Gatt, Adir Shaulov, Eirini Katodritou, Theodora Triantafyllou, Noa Lavi, Anastasia Pouli, Anastasia Sioni, Iuliana Vaxman, Miri Zektser, Chezi Ganzel, Noam Benyamini, Svetlana Trestman, Tomer ziv Baran, Yael C Cohen, Irit Avivi
Journal: Blood (2018)
Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial
Authors: Thomas Lung, Stephen Jan, H Asita de Silva, Rama Guggilla, Pallab K Maulik, Nitish Naik, Anushka Patel, Arjuna P de Silva, Senaka Rajapakse, Gotabhaya Ranasinghe, Dorairaj Prabhakaran, Anthony Rodgers, Abdul Salam, Vanessa Selak, Sandrine Stepien, Simon Thom, Ruth Webster, Tracey Lea-Laba
Journal: The Lancet Global Health (2019)

BackgroundElevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy.MethodsWe did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years.FindingsThe triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (−28·67 to 5714·24) per DALY averted over a 10-year period.InterpretationCompared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension management in Sri Lanka should be supported to address the high population burden of cardiovascular disease.FundingAustralian National Health and Medical Research Council.