tbuckley/cabot-search huggingface dataset:
Sex-based differences in gallbladder cancer: An analysis of 257 patients.
Authors: Vishal Gupta, Abhijit Chandra, Saket Kumar, Hunaid Hatimi, Rahul R, Vivek Gupta
Journal: Journal of Clinical Oncology (2014)

e15095 Background: Gallbladder cancer (GBC) predominantly affects females. This sex based preference may be due to cholelithiasis, sex hormones or genetic factors. Objective of this study was to assess the sex based differences in various clinicopathological parameters in GBC. Methods: Patients with GBC admitted to the hospital between January 2009 and December 2013 were included in the study while patients managed in outdoor clinic were excluded. Retrospective analysis of 257 patients (males 69, females 188) was performed with respect to various clinicopathological parameters to assess sex based differences. Statistical analysis was performed using t test and χ2 or Fisher’s test, and survival was estimated using Kaplan-Meir method and log-rank test was used to analyze the difference between survival curves. Results: At presentation 79.7% patients had abdominal pain (mean duration 4.65±9.32 months), 54.4% had jaundice (mean duration 2.07±2.79 months), 70 (27.3%) had metastatic disease and 73 (28.4%) had locally advanced unresectable (LAUR) disease. At surgical exploration (n=114) 36 patients had metastatic and 21 had LAUR disease. Finally 57 patients (22.1%) underwent curative resection. With respect to sex (males vs females), no significant difference was found in age (mean 52.12±12.55 vs 49.93±11.73 years, p=0.19), presence of pain (76.8% vs 80.9%, p= 0.58) or its duration (mean 5.0± 7.0 vs 4.53±10.05 months, p=0.78), jaundice (55.1% vs 55.3%, p=0.97) or its duration (mean 2.50±4.60 vs 1.91±1.76 months, p=0.33), anorexia (33.3% vs 29.3%, p=0.63), weight loss (26.1% vs 23.4%, p=0.77), gallstones (58% vs 68.1%, p=0.15), advanced (N1/T4) disease (15.4% vs 27.2%, p=0.48), resectability (18.8% vs 23.4%, p=0.54) and tumor grade (well vs moderate/poor, 80% vs 43.2%, p=0.07). Median survival was 38 months for both sexes with significant differences in survival curves (p=0.03) favoring females. Conclusions: Clinicopathological characteristics of GBC do not differ in male and female patients. However, females have better survival than males.
Quantification of T790M mutation in <i>EGFR</i>-mutant lung adenocarcinoma with nanofluidic digital PCR arrays.
Authors: Kazutoshi Isobe, Yoshinobu Hata, Naobumi Tochigi, Kyohei Kaburaki, Takashi Makino, Hahjime Otsuka, Keita Sato, Go Sano, Keishi Sugino, Susumu Sakamoto, Yujiro Takai, Akira Iyoda, Sakae Homma
Journal: Journal of Clinical Oncology (2014)

11054 Background: Patients with EGFR-mutant lung adenocarcinoma develop acquired resistance to EGFR-TKI (TKI) in 10-16 months. About 50% of patients with acquired resistance to TKI have T790M mutation (T790M). However, repeat biopsy to monitor mutation status is not practical. Digital PCR arrays limiting dilution of DNA and can detect single molecules, thus enabling extremely sensitive detection and quantification. We evaluated the usefulness of nanofluidic digital PCR arrays in EGFR-mutant lung adenocarcinoma. Methods: We enrolled 12 patients with primary lung adenocarcinoma and EGFR mutation (exon 19 deletion in 8; L858R in 4) at the pretreatment primary site who acquired resistance to gefitinib. Patients were divided into 2 groups according to T790M status after TKI resistance, as confirmed by rebiopsy. Nanofluidic digital PCR arrays (BioMark HD System, Fluidigm Japan K.K. Tokyo, Japan) were used to quantify T790M in genomic DNA from the pretreatment primary site and serum cell-free DNA (cfDNA) after TKI resistance. Numbers of mutant molecules were estimated by the number of positive chambers in the digital PCR chip and were corrected using the Poisson equation. We assessed the ratio of the number of positive T790M molecules to the number of positive exon 2 molecules. Results: The digital PCR array detected and quantified T790M (0.00-1.21%) in samples from the pretreatment primary site and serum cfDNA after TKI resistance. On digital PCR, the rebiopsy-positive T790M group (n=4) had a significantly higher quantified T790M at the pretreatment primary site than did the T790M-negative group (n=8) (0.59±0.58% vs 0.07±0.09%, p < 0.001). However, the results of analysis of serum cfDNA after TKI resistance did not significantly differ (0.09±0.14% vs 0.05±0.15%, respectively, p = 0.41). T790M at the pretreatment primary site as quantified by digital PCR significantly positively correlated with progression-free survival (PFS) after gefitinib therapy (r = 0.71, p < 0.001). Conclusions: Use of digital PCR to quantify T790M at the primary site of EGFR-mutant lung adenocarcinoma was useful for predicting T790M positivity in rebiopsies after TKI resistance and PFS after gefitinib therapy.
Efficacy and Safety of Spironolactone in Patients With HFpEF and Chronic Kidney Disease
Authors: Iris E Beldhuis, Peder L Myhre, Brian Claggett, Kevin Damman, James C Fang, Eldrin F Lewis, Eileen O'Meara, Bertram Pitt, Sanjiv J Shah, Adriaan A Voors, Marc A Pfeffer, Scott D Solomon, Akshay S Desai
Journal: JACC Heart Failure (2018)
Investigating Patient Characteristics and Outcomes of Myelofibrosis Patients with Hyperleukocytosis
Authors: Savan Shah, Chetasi Talati, Najla Al Ali, Eric Padron, David A Sallman, Kendra L. Sweet, Jeffrey E. Lancet, Alan F. List, Rami S. Komrokji, Andrew T Kuykendall
Journal: Blood (2018)
Hyperfiltration during early childhood precedes albuminuria in pediatric sickle cell nephropathy
Authors: Jeffrey D. Lebensburger, Inmaculada Aban, Brandi Pernell, Malgorzata Kasztan, Daniel I. Feig, Lee M. Hilliard, David J. Askenazi
Journal: American Journal of Hematology (2018)

Abstract Background In patients with diabetes mellitus, hyperfiltration precedes the development of albuminuria. Pediatric sickle cell anemia (SCA) patients have a high prevalence of hyperfiltration and albuminuria during early childhood and adolescence. We tested the hypothesis that hyperfiltration precedes the development of albuminuria in a longitudinal pediatric SCA cohort. Methods We identified 91 participants with HbSS or SB0 thalassemia 5‐21 years of age enrolled in a longitudinal sickle cell nephropathy cohort study who had a cystatin C measured during early childhood (4‐10 years of age). Early hyperfiltration was defined as a mean eGFR &gt;180 mL/min/1.73m 2 using cystatin C obtained from 4 to 10 years of age. Persistent albuminuria was defined as an albumin to creatinine ratio &gt; 30 mg/g on two of three untimed urine specimens. Time to event analysis estimated survival curves for participants with and without hyperfiltration using Kaplan‐Meier curves and used logrank test for categorical variables to assess the association with time to development of the first episode persistent albuminuria. Results Persistent albuminuria occurred more often and at an earlier age in participants with early hyperfiltration compared to those without early hyperfiltration (log‐rank, P = .004). Participants who developed albuminuria have a significant increase in their eGFR during childhood ( P = .003) as compared to participants who have not yet progressed to albuminuria ( P = .26). For every 1 g/dL increase in hemoglobin, the hazard ratio for developing persistent proteinuria decreased by 0.56 (95% CI: 0.3, 1.06, P = .07). Conclusion Hyperfiltration precedes the development of persistent proteinuria in pediatric SCA patients. Intervention strategies should target lowering eGFR during early childhood.
A phase 1b trial of PI3K inhibitor copanlisib (BAY 80-6946) combined with the allosteric-MEK inhibitor refametinib (BAY 86-9766) in patients with advanced cancer.
Authors: Ramesh K. Ramanathan, Daniel D. Von Hoff, Ferry Eskens, George R. Blumenschein, Donald A. Richards, Frank Gary Renshaw, Prabhu Rajagopalan, Andrea Kelly, Carol Elaine Pena, Klaus B. Mross
Journal: Journal of Clinical Oncology (2014)

2588 Background: Dual inhibition of the PI3K and MAPK signaling pathways is a promising strategy for optimal anticancer therapy. In this phase 1b trial we determined the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of the combination of the pan-PI3K inhibitor copanlisib (C) and the allosteric-MEK inhibitor refametinib (R). Methods: Eight dose cohorts combining increasing doses and varying schedules of C (0.2-0.8 mg/kg IV; 3W on/1W off and QW) and R (30 mg and 50 mg bid po; continuous or 4 days on/3 days off) on 28-day cycles were studied. PK of C was assessed on Days 1 and 15 and PK of R on Days 14 and 15. In a 15-patient mutation-selected expansion cohort in mixed solid tumors, plasma samples are being assessed for tumor mutations (N-RAS, K-RAS, B-RAF, and PI3KCA) in circulating DNA by BEAMing and paired tumor biopsies undergoing biomarker analyses (including pERK and pAKT). Results: The study has completed accrual, with 49 patients treated in the dose escalation part of this study, of which 44 were evaluable for safety and efficacy. DLT’s included Grade 3 AST or ALT elevation (n=2), hyperglycemia (1); hypertension (2); diarrhea (2), mucositis (2) and rash (1). The most common drug-related adverse events (>20%) in the dose escalation part were: diarrhea, nausea, hyperglycemia, fatigue, rash, anorexia, and hypertension. The MTD and RP2D for the C + R combination were: C 0.4 mg/kg IV QW and R 30 mg bid po. These doses are below the MTDs of either compound alone: C 0.8 mg/kg IV 3wks on/1 wk off and R 50 mg bid or 100 mg qd po. PK exposures of R and C were not affected by concomitant administration. Clinical activity included one PR in a patient with endometrial cancer, and stable disease lasting >4 cycles in 9 patients. Treatment discontinuations were due to disease progression (n=13), drug or tumor-related adverse events (n=24), or patient/physician discretion (n=12). Preliminary signals of antitumor activity have been observed in the fully accrued expansion cohort. Conclusions: The C+R combination was generally well tolerated with the MTD and RP2D below the individual tolerated doses of either compound. Preliminary evidence of clinical efficacy has been observed. Clinical trial information: NCT01392521.
Palliative outpatient care in rural Germany: Assessment of efficiency and statistics of a single center institution in Bavaria.
Authors: Tobias Weiglein, Ursula Vehling-Kaiser, Daniela Illig, Florian Kaiser
Journal: Journal of Clinical Oncology (2014)

e20549 Background: According to recent studies, Germany will face 14% more cases of cancer in 2020 than in 2008. Especially rural areas will have severe further problems due to the already existent lack of oncologists and palliative care specialists. This is in particular problematic for rural Bavaria. Palliative outpatient services (POS) for terminally ill patients have grown in numbers over the last years, but the ever increasing demand, especially in regions lacking infrastructure, is not met. Statistical data specifying the exact need of services and personnel are yet not established. To define the demands more closely, we prospectively reviewed the initial activity of a new POS attached to a European Society for Medical Oncology-designated oncologic center in rural Bavaria, Landshut. Methods: We prospectively assessed patient statistics from January till December 2013 of the POS Landshut, the only professional institution catering to palliative patients at home in this area. Data was collected centrally, e.g. number of patients, demographic characteristics, survival and initial symptom burden were evaluated. Also, quality of life assessment of family members are undergoing. Results: In 2013, the POS Landshut cared for an overall of 212 Patients (48% female, 52% male) referred by a total of 35 different health practitioners. Most patients were referred by oncologic practices, followed by general practitioners and hospitals. 90% had a malignant disease, 6% neurologic and 4% other illnesses. The median age at inclusion was 72 years (Range 30 to 96). The average distance covered was 23 km per patient one way, ranging from 3 to 78 km. Most patients (82%) were able to die at home while included in the POS after a median time of 23 days (2 till NR). The monthly capacity of 20 patients was constantly reached with a median 19,5 patients in care at all times. Conclusions: The POS is an important institution for critically ill patients with or without malignant diseases and has become an important link between in- and outpatient palliative health care. More and bigger POS are needed in rural Bavaria to meet the increasing demand of palliative care at home.
One-view breast tomosynthesis vs two-view mammography: a methodological issue – Authors' reply
Authors: Sophia Zackrisson, Kristina Lång, Aldana Rosso, Kristin Johnson, Magnus Dustler, Daniel Förnvik, Hannie Förnvik, Hanna Sartor, Pontus Timberg, Anders Tingberg, Ingvar Andersson
Journal: The Lancet Oncology (2019)
Comparison of the Transcriptomic Signature of Pediatric Vs. Adult CML and Normal Bone Marrow Stem Cells
Authors: Hee-Don Chae, Lara C. Murphy, Michele Donato, Alex G. Lee, E. Alejandro Sweet-Cordero, Parveen Abidi, Henrique Bittencourt, Norman J. Lacayo, Gary Van Houten Dahl, Catherine Aftandilian, Kara L. Davis, Min Huang, Nathan Sumarsono, Michele Redell, Cecilia H. Fu, I-Ming L. Chen, Todd A Alonzo, Elizabeth A. Eklund, Jason R. Gotlib, Purvesh Khatri, Nobuko Hijiya, Kathleen M. Sakamoto
Journal: Blood (2018)
The Impact of Lenalidomide, Bortezomib, and Dexamethasone Treatment on Health-Related Quality of Life in Transplant-Eligible Patients with Newly-Diagnosed Multiple Myeloma: Results from the IFM/DFCI 2009 Trial
Authors: Murielle Roussel, Benjamin Hebraud, Cyrille Hulin, Aurore Perrot, Denis Caillot, Margaret Macro, Bertrand Arnulf, Karim Belhadj, Laurent Garderet, Thierry Facon, Shien Guo, Arman Altincatal, Sujith Dhanasiri, Xavier Leleu, Philippe Moreau, Michel Attal
Journal: Blood (2018)
Treatment of HIV-associated plasmablastic lymphoma: A single-center experience with 25 patients.
Authors: Ibrahim Fuad Ibrahim, Gabriel A. Shapiro, Harris V. K. Naina
Journal: Journal of Clinical Oncology (2014)

8583 Background: Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of B-cell lymphoma with a predominant occurrence in patients with HIV and other immune compromised states. It commonly affects the jaw and oral cavity but has also been described involving the gastrointestinal tract, bone, bone marrow, and lymph nodes. The historical treatment regimens have typically included CHOP, but more recently dose-adjusted EPOCH has become the standard for HIV-associated lymphomas. It is unclear if regimens other than CHOP can significantly improve the outcome in patients with PBL. Methods: We identified 25 patients with PBL at Parkland Hospital treated between 2000 to 2012. Data regarding patient age, gender, HIV status, initiation of antiretroviral therapy, immunophenotype, EBV status, administration of radiotherapy and primary site of presentation were recorded. Log-rank test was used to assess differences in survival by treatment regimen. Results: The median age at presentation was 44 years with a 4:1 male predominance. Most (92%) were infected with HIV and had a median CD4+ count of 87 cells/mm3. A minority of patients (32%) were on antiretroviral therapy at the time of diagnosis. The most common primary sites of disease were oral/maxillofacial sites and the gastrointestinal tract with most patients presenting with stage III or IV disease (64%). EBV was detected in the majority of cases (91%) and HHV-8 was detected in none of the cases. CD20 positivity was rare (12%). MYC rearrangements were described in 32% of the cases. Chemotherapy was used to treat most patients (76%) with EPOCH being the most common treatment choice (56%). Radiotherapy was administered in 28% of patients. Primary refractory disease was observed in 16% of the patients. The median overall survival observed in all patients who received chemotherapy was 11.6 months (range 2-63 months). Those who were treated with EPOCH demonstrated a better median overall survival (17 months) compared to those treated with CHOP and CHOP-like regimens (7 months, p=0.04). Conclusions: This retrospective single center study suggests that EPOCH may improve survival in PBL.
Should Viscous Fiber Supplements Be Considered in Diabetes Control? Results From a Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Elena Jovanovski, Rana Khayyat, Andreea Zurbau, Allison Komishon, Nourah Mazhar, John L. Sievenpiper, Sonia Blanco Mejia, Hoang Vi Thanh Ho, Dandan Li, Alexandra L. Jenkins, Lea Duvnjak, Vladimir Vuksan
Journal: Diabetes Care (2019)

Evidence from randomized controlled trials (RCTs) suggests that viscous dietary fiber may offer beneficial effects on glycemic control and, thus, an improved cardiovascular disease risk profile. Our purpose was to conduct a systematic review and meta-analysis of RCTs to synthesize the therapeutic effect of viscous fiber supplementation on glycemic control in type 2 diabetes.MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through 15 June 2018. We included RCTs ≥3 weeks in duration that assessed the effects of viscous fiber on markers of glycemic control in type 2 diabetes. Two independent reviewers extracted data. Data were pooled using the generic inverse variance method and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall certainty of the evidence.We identified 28 eligible trial comparisons (n = 1,394). Viscous fiber at a median dose of ∼13.1 g/day significantly reduced HbA1c (MD -0.58% [95% CI -0.88, -0.28]; P = 0.0002), fasting blood glucose (MD -0.82 mmol/L [95% CI -1.32, -0.31]; P = 0.001), and HOMA-insulin resistance (IR) (MD -1.89 [95% CI -3.45, -0.33]; P = 0.02) compared with control and in addition to standard of care. The certainty of evidence was graded moderate for HbA1c, fasting glucose, fasting insulin, and HOMA-IR and low for fructosamine.Viscous fiber supplements improve conventional markers of glycemic control beyond usual care and should be considered in the management of type 2 diabetes.
Response to: ‘Catching the falling star: points to consider when using propensity scores’ by Ouyang <i>et al</i>
Authors: Sytske Anne Bergstra, Cornelia F Allaart, Robert B M Landewé
Journal: Annals of the Rheumatic Diseases (2018)

We would like to thank Dr Ouyang1 for his thoughtful response to our article, including additional suggestions regarding the use of the multiple (or generalised) propensity score (PS), which we are sure will be helpful for other researchers who plan to use this technique.2 We agree with the mentioned suggestions and will provide some additional clarifications.

Like virtually every method used to adjust for bias in observational data, a multiple PS is dependent on the ignorability assumption and assumes that all important confounders are measured and included. Although in practice it is probably impossible to know all confounders, this emphasises the importance of …
Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial
Authors: Rachel B Jones, Thomas F Hiemstra, Jose Ballarin, Daniel Engelbert Blockmans, Paul Brogan, Annette Bruchfeld, Maria C Cid, Karen Dahlsveen, Janak de Zoysa, Georgína Espigol-Frigolé, Peter Lanyon, Chen Au Peh, Vladimir Tesar, Augusto Vaglio, Michael Walsh, Dorothy Walsh, Giles Walters, Lorraine Harper, David Jayne
Journal: Annals of the Rheumatic Diseases (2019)

Cyclophosphamide induction regimens are effective for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but are associated with infections, malignancies and infertility. Mycophenolate mofetil (MMF) has shown high remission rates in small studies of AAV.We conducted a randomised controlled trial to investigate whether MMF was non-inferior to cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients were randomly assigned to MMF or pulsed cyclophosphamide. All patients received the same oral glucocorticoid regimen and were switched to azathioprine following remission. The primary endpoint was remission by 6 months requiring compliance with the tapering glucocorticoid regimen. Patients with an eGFR <15 mL/min were excluded from the study.At baseline, ANCA subtype, disease activity and organ involvement were similar between groups. Non-inferiority was demonstrated for the primary remission endpoint, which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in the cyclophosphamide group (risk difference 5.7%, 90% CI -7.5% to 19%). Following remission, more relapses occurred in the MMF group (23 patients, 33%) compared with the cyclophosphamide group (13 patients, 19%) (incidence rate ratio 1.97, 95% CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and 48% of the MMF group. Serious infections were similar between groups (26% MMF group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3).MMF was non-inferior to cyclophosphamide for remission induction in AAV, but resulted in higher relapse rate.NCT00414128.
T Cells Engineered with a Novel Chimeric Receptor Demonstrate Durable In Vivo Efficacy Against Disseminated Multiple Myeloma
Authors: Ksenia Bezverbnaya, Vivian Lau, Craig Aarts, Galina Denisova, Arya Afsahi, Carole Evelegh, Derek Cummings, Christopher Helsen, Jonathan Bramson
Journal: Blood (2018)
A Phase 1b Study of Intravenous Vedolizumab Plus Standard of Care for Graft-Versus-Host Disease Prophylaxis in Subjects Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies: 6-Month Results
Authors: Yi-Bin Chen, Nirav N Shah, Anne S. Renteria, Corey S. Cutler, Johan Jansson, Mona Akbari, Chunlin Chen, Syed Quadri, Andrejus Parfionovas, Steven Devine
Journal: Blood (2018)