tbuckley/cabot-search huggingface dataset:
Case report of multiple pustules of the bilateral lower limbs caused by a granulocyte colony-stimulating factor-producing solid pseudopapillary tumour of the pancreas
Authors: Y. Iwata, T. Kobayashi, M. Kuroda, Y. Mizoguchi, M. Arima, S. Numata, S. Watanabe, A. Yagami, K. Matsunaga, K. Sugiura
Journal: British Journal of Dermatology (2016)

Here we report a rare case of neutrophilic dermatoses related to a granulocyte colony‐stimulating factor (G‐CSF)‐producing solid pseudopapillary tumour (SPT). The patient was a 39‐year‐old woman presenting with scattered pustules and crusts of the palms, heels and thighs and plaques of the bilateral lower legs. The skin biopsy revealed dense neutrophil infiltration in the epidermis to the dermis. A pancreatic head tumour was detected using computed tomography. A pathological examination of the resected specimen suggested an SPT. As the skin eruption promptly disappeared after SPT resection, we hypothesized that SPT secretes growth factors including epidermal growth factor (EGF) and G‐CSF. The SPT cells stained positive for both EGF and G‐CSF tumour cells. The serum levels of interleukin (IL)‐6 and IL‐10 and tumour necrosis factor‐α were within normal limits before and after the SPT resection. In contrast, the serum IL‐8, EGF and G‐CSF levels decreased after the SPT resection. This is a rare case of neutrophilic dermatoses related to a G‐CSF‐producing SPT. The present case suggests that physicians should be aware that a G‐CSF‐producing tumour is a differential diagnosis to consider in patients with unusual aseptic pustulosis.
Meta-analysis of randomized phase II and phase III trials of gemcitabine with/without S-1 in Asian patients with advanced pancreatic cancer.
Authors: Geoffrey Yuyat Ku, Benjamin Haaland, Tatsuya Ioka, Hiroyuki Isayama, Yousuke Nakai, Ann-Lii Cheng, Takuji Okusaka, Gilberto de Lima Lopes
Journal: Journal of Clinical Oncology (2012)

311 Background: Advanced pancreatic cancer (PC) is a virulent disease, where gemcitabine is considered the standard-of-care. A recent phase III evaluation demonstrated superiority of FOLFIRINOX (bolus and infusional 5-fluorouracil (FU), irinotecan, oxaliplatin) in patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1. Recently, three studies were presented in abstract form, comparing gemcitabine/S-1 (GS) to gemcitabine. S-1 is a mixture of tegafur (an oral 5-FU prodrug), a dihydropyrimidine dehydrogenase inhibitor and an agent designed to reduce the gastrointestinal toxicity of 5-FU. All three trials demonstrated significant improvements in progression-free survival (PFS) while one study also showed a statistically significant improvement in overall survival (OS). Methods: We performed a meta-analysis of the three trials. Results: Seven hundred and seventy patients were randomized to receive GS vs. gemcitabine; 75% had metastatic disease and 65% had an ECOG PS of 0. GS was associated with superior RR (hazard ratio (HR) 0.348, p=3.06×10 -7 ), PFS (HR 0.64, p=7.26×10 -9 ) and OS (HR 0.79, p=2.47×10 -2 ) compared to gemcitabine. Patients receiving GS were more likely to experience nausea, diarrhea, rash and stomatitis (mostly grade 1/2); neutropenic fever occurred in &lt;2% of patients. One study demonstrated superior quality-of-life for GS. Conclusions: GS should be considered a first-line option for the treatment of advanced PC in Asian patients. This regimen should serve as the reference for future trials and comparison with FOLFIRINOX in patients with ECOG PS ≤1 is warranted.
Mathematical modeling of atopic dermatitis reveals “double-switch” mechanisms underlying 4 common disease phenotypes
Authors: Elisa Domínguez-Hüttinger, Panayiotis Christodoulides, Kosuke Miyauchi, Alan D. Irvine, Mariko Okada-Hatakeyama, Masato Kubo, Reiko J. Tanaka
Journal: Journal of Allergy and Clinical Immunology (2016)

The skin barrier acts as the first line of defense against constant exposure to biological, microbial, physical, and chemical environmental stressors. Dynamic interplay between defects in the skin barrier, dysfunctional immune responses, and environmental stressors are major factors in the development of atopic dermatitis (AD). A systems biology modeling approach can yield significant insights into these complex and dynamic processes through integration of prior biological data.We sought to develop a multiscale mathematical model of AD pathogenesis that describes the dynamic interplay between the skin barrier, environmental stress, and immune dysregulation and use it to achieve a coherent mechanistic understanding of the onset, progression, and prevention of AD.We mathematically investigated synergistic effects of known genetic and environmental risk factors on the dynamic onset and progression of the AD phenotype, from a mostly asymptomatic mild phenotype to a severe treatment-resistant form.Our model analysis identified a "double switch," with 2 concatenated bistable switches, as a key network motif that dictates AD pathogenesis: the first switch is responsible for the reversible onset of inflammation, and the second switch is triggered by long-lasting or frequent activation of the first switch, causing irreversible onset of systemic TH2 sensitization and worsening of AD symptoms.Our mathematical analysis of the bistable switch predicts that genetic risk factors decrease the threshold of environmental stressors to trigger systemic TH2 sensitization. This analysis predicts and explains 4 common clinical AD phenotypes from a mild and reversible phenotype through to severe and recalcitrant disease and provides a mechanistic explanation for clinically demonstrated preventive effects of emollient treatments against development of AD.
Phase I trial sunitinib plus everolimus in patients with metastatic renal cell carcinoma (mRCC).
Authors: A. M. Molina, D. R. Feldman, M. S. Ginsberg, P. Fischer, M. J. Trinos, S. Patil, R. J. Motzer
Journal: Journal of Clinical Oncology (2011)

311 Background: Sunitinib a targeted tyrosine kinase inhibitor and everolimus an mTOR inhibitor both inhibit hypoxia-induced factor-dependent signaling and have activity in advanced renal cell carcinoma (RCC). The safety and maximum tolerated dose (MTD) of sunitinib in combination with everolimus was assessed in this phase I trial. Methods: Cohorts of 3–6 patients with mRCC received sunitinib at 37.5 or 50 mg daily for 4 weeks followed by 2 weeks off with everolimus administered either daily (2.5 or 5 mg) or weekly (20 or 30 mg). Dose-limiting toxicities (DLTs) were assessed in the first 6-week cycle to determine MTD. Results: 20 patients (13 clear cell and 7 non-clear cell RCC) were enrolled in five cohorts. Both patients in the 2 nd dose level (everolimus 5 mg daily, sunitinib 37.5mg) experienced grade 3 DLT (thrombocytopenia and mucositis; vomiting). With weekly everolimus dosing, the MTD was everolimus 30 mg /sunitinib 37.5 mg (4 th dose level). However, only one of six patients at this dose level tolerated treatment beyond 4 cycles. Grades 3 and 4 toxicities observed with chronic treatment included infection, gastrointestinal hemorrhage, and pulmonary embolism. A total of six patients were treated with everolimus 20b mg weekly/37.5 mg sunitinib (3 rd dose level) with better tolerance as chronic therapy. Overall, 5 out of 20 patients achieved a partial response including 3 patients with non-clear cell histology. Conclusions: Partial responses were observed in both clear cell and non-clear cell histologies. However, due to toxicity the combination of sunitinib and everolimus could not be administered at full doses. [Table: see text]
Early evidence of increasing national mastectomy rates for the treatment of breast cancer.
Authors: U. Mahmood, A. L. Hanlon, M. Koshy, R. Buras, S. Chumsri, K. H. Tkaczuk, S. Cheston, W. Regine, S. J. Feigenberg
Journal: Journal of Clinical Oncology (2011)

136 Background: The use of mastectomy for the treatment of breast cancer has declined since initial randomized trials demonstrated equivalent survival with breast conservation therapy. Recent single institution series, however, have reported increasing mastectomy rates within the past decade. Methods: In order to verify these findings at the national level, we analyzed data from the Surveillance, Epidemiology, and End Results database, including women diagnosed with T1-2 N0-3 M0 breast cancer from 2000 to 2007. We evaluated therapeutic mastectomy rates by the year of diagnosis and performed a multivariable logistic regression analysis to determine predictors of mastectomy as the treatment choice. Results: A total of 228,240 patients met the entry criteria. The proportion of women treated with mastectomy decreased from 40.3% to 35.6% between 2000 and 2005. Subsequently, the mastectomy rate increased to 37.9% in 2007 (p &lt; 0.0001). The mastectomy rate in 2007 was the highest since 2002 (38.6%). A reversal in previously declining mastectomy rates was noted in nearly all cohorts, but was most pronounced among younger women. Multivariable analysis found that age, race, marital status, geographic location, involvement of multiple regions of the breast, lobular histology, increasing tumor size, lymph node positivity, increasing grade, negative hormone receptor status, and synchronous diagnosis of an ipsilateral or contralateral breast cancer were independent predictors of mastectomy. Additionally, multivariable analysis confirmed that women diagnosed in 2007 were more likely to undergo mastectomy than women diagnosed in 2005 (HR = 1.14, CI: 1.09 to 1.18, p &lt; 0.0001). Conclusions: There is evidence of a reversal in the previously declining national mastectomy rates, with the mastectomy rate reaching a nadir in 2005 and subsequently rising. Further follow-up to confirm this trend and investigation to determine the underlying cause of this trend and its impact on outcomes are warranted.
Treatment-related changes in neurobehavioral symptoms.
Authors: S. K. Patel, E. Beier, A. Davtyan, A. Meier, M. R. Palomares, A. Hurria, S. Bhatia
Journal: Journal of Clinical Oncology (2011)

167 Background: Neurobehavioral outcomes, such as fatigue and neurocognitive dysfunction, are disabling side effects in a subgroup of breast cancer (BC) patients. Longitudinal studies with appropriate controls to dissociate treatment-related effects from those experienced by healthy post-menopausal women are sparse, and virtually all define “pre-treatment” baseline as prior to adjuvant therapy, but following surgery. Given the phenomenon of “postoperative cognitive dysfunction” reported in older patients undergoing major surgery, we are evaluating treatment-related impact using pre-surgery assessment as the baseline. Methods: Eligible post-menopausal BC patients are assessed prior to any local or systemic treatment and one month after completion of treatment (surgery, radiation and/or chemotherapy). Healthy controls (HC) are age-matched 1:2-3 and tested at similar time intervals. Currently 130 BC and 60 HC are enrolled; results for 80 BC and 30 HC who have reached Time 2 are available (Mean time between assessments = 143 days, SD = 93). Results: Interim analyses using repeated measures ANOVA, controlling for age and education differences, show that the BC group declined in verbal memory functioning post-treatment relative to baseline, while the HC group improved due to practice effects (F(1, 102) = 3.43, p = .061). A similar interaction effect is observed for executive functioning, where the BC group failed to benefit from practice effects to the same degree as did HC (F(1, 102) = 6.04, p = .016). Anxiety but not depression was significantly elevated at baseline and decreased post treatment in BC patients treated with and without chemotherapy (F (1, 102) = 6.85, p = .010). Fatigue did not significantly change for the BC group; however, it was significantly higher than HC at baseline (t =2.77, p = .01) and remained high at the post-treatment measurement. Conclusions: Significant declines in neurocognitive functioning soon after completion of BC treatment were observed compared to healthy post-menopausal women. This observation did not appear to be due to mood disturbance, as anxiety and depression decreased following treatment. Our data also suggest that fatigue is present even prior to any cancer treatment.
A Phase I Trial of Pomalidomide, Bortezomib (Velcade), and Dexamethasone (PVD) As Initial Treatment of AL Amyloidosis and Light Chain Deposition Disease
Authors: Jeffrey Zonder, Christiane Houde, Sascha Tuchman, Vishal Kukreti, Vaishali Sanchorawala, Silva Pregja, Kathy A Reichel, Steven M Burt, Colleen Neveux, Jeffrey Matous
Journal: Blood (2014)
Intraprostatic vaccine administration in patients with locally recurrent prostate cancer.
Authors: C. Heery, P. A. Pinto, J. Schlom, K. Y. Tsang, R. A. Madan, D. Poole, M. Vergati, B. Walter Rodriguez, M. Merino, J. L. Gulley
Journal: Journal of Clinical Oncology (2011)

141 Background: PSA-TRICOM is a cancer vaccine consisting of recombinant poxviruses with transgenes for PSA and 3 T cell costimulatory molecules (TRICOM). A multicenter randomized vector controlled phase II study showed an 8.5 month improvement in median survival in men with metastatic CRPC. Preclinical studies showed intratumoral administration of TRICOM vaccines may improve anti-tumor outcomes. This study was intended to show safety of intraprostatic (i.p.) vaccine administration. 2° goals included immunologic and tumor response. Methods: 21 pts were enrolled with locally recurrent prostate cancer after radiation into 5 cohorts and received initial vaccination with s.c. recombinant vaccinia (rV)-PSA-TRICOM and booster i.p. recombinant fowlpox (rF)-PSA-TRICOM. Cohorts 3-5 also received i.p. rF-GM-CSF. Cohort 5 received concurrent s.c. and i.p. boosters. Priming was given on day 1, and boosters were given on days 29, 57, and 85. Pts had pre- and post-treatment prostate biopsies. Tumor infiltrate was evaluated when adequate tissue was available. PBMCs were analyzed by ELISPOT for response to PSA and 3-color flow cytometry to characterize regulatory T cells (Treg) or effector T cells. Treg suppression function was assayed by suppression of the CD4 + effector T cell proliferation. Results: Only 1 grade 3 toxicity occurred, a transient fever. Most common grade 2 adverse events for all doses were fever (14.5%) and injection-site reactions (21%). 15 of 21 pts had stable or improved PSA on study, and 16 of 21 pts had stable or improved PSA doubling time. Post-vaccination, 4 of 8 evaluable pts had immunological response by ELISPOT assay and 11 of 15 pts had decreased (n=8) or stable (n=3) Treg function. A paired t-test of 13 biopsies pre- and post- vaccination showed significant increases in immune infiltrates within tumors after vaccination. CD4 + cells increased from 1.3 → 13.1/high power field (hpf). CD8 + cells rose from 6.4 → 14/hpf. Conclusions: I.p. administration of PSA-TRICOM is safe, feasible and can generate a substantial immunologic response. Improved PSA kinetics and intense post-vaccination immune infiltrates were seen in the majority of pts. Trials of i.p. PSA-TRICOM examining clinical endpoints are warranted. No significant financial relationships to disclose.
Cladribine (CdA) Gives Longer Response Duration Than Fludarabine (F) and High-Dose Intermittent Chlorambucil (Chl) as First-Line Treatment of Symptomatic Chronic Lymphocytic Leukemia (CLL). First Results from the International Randomized Phase III Trial.
Authors: Karin A. Karlsson, Mats Strömberg, Viggo Jönsson, Stephen P. Mulligan, Jan Liliemark, Gunnar Juliusson
Journal: Blood (2007)
How does consciousness for action relate to attention for action?
Authors: Elizabeth A. Franz
Journal: Behavioral and Brain Sciences (2016)

The interesting target article by Morsella et al. addresses critical issues that impact our understanding of consciousness. It is surprising, however, to see no treatment of the relationship between attention and consciousness, particularly given available models. Whether olfaction is most suitable as a model system to study consciousness for action also seems questionable. These issues are elaborated in the present commentary.
Can PSA doubling time exactly predict the candidates for active surveillance in patients with low-risk prostate cancer?
Authors: Satoru Maruyama, Nobuo Shinohara, Takashige Abe, Ataru Sazawa, Katsuya Nonomura
Journal: Journal of Clinical Oncology (2012)

65 Background: Currently, there are few well-validated data of PSA kinetics (PSA doubling time [PSADT] and PSA velocity) in active surveillance protocols. The objective of the study was to elucidate whether PSADT could predict patients with low-risk prostate cancer suitable for active surveillance (AS). Methods: The study included 149 consecutive patients treated with radical prostatectomy (RP). We selected patients who could be candidates for AS (PSA≤10ng/ml and Gleason score (GS)≤3+3 and cT1-2N0M0). PSA had been measured two times at least in a year before surgery. After all, from April 2000 to March 2008, we retrospectively reviewed a total of 47 patients (median age were 64 years, range: 53-75). Patients were divided into the following two groups: patients whose PSADT&lt;36 months (Rapid group) and the others (Non-rapid group). We determined the respective rates of upgrading, upstaging and biochemical relapse-free survival (bRFS) in each group. Risk factors were evaluated using a Cox proportional hazards model. Results: In the whole specimen of 47 pts, upgraded to Gleason score 7-8, extracapsular extension (ECE: pT3a disease), seminal vesicle involvement and upstaged were 23 (49%), 7 (15%), none (0%) and 7 (15%), respectively. No statistical significance was observed in occurrence rates of upgrading and upstaging between Rapid group (56%, 19%) and Non-rapid group (45%, 13%). There was no significant difference in biochemical-free survival rates in two groups (5-year bRFS were 71% and 77%, respectively). The Cox proportional hazards analysis demonstrated that any pre-operative factors including PSADT were not significant risk factors for biochemical relapse. Conclusions: Our findings revealed that pre-opeative PSADT did not reliably predict pathology and prognosis after RP in those who were candidates for AS. PSADT is not suitable for selection criteria and for monitoring on active surveillance.
Effect of G-CSF prophylaxis on the occurrence of neutropenia in men receiving cabazitaxel plus prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in the TROPIC study.
Authors: M. Ozguroglu, S. Oudard, A. O. Sartor, S. Hansen, J. H. Machiels, L. Shen, J. S. De Bono
Journal: Journal of Clinical Oncology (2011)

144^ Background: The phase III TROPIC study showed that cabazitaxel plus prednisone (CbzP) improves survival compared with mitoxantrone plus prednisone (MP) in men with mCRPC who progressed after docetaxel-based therapy (HR 0.70; p&lt;0.001; Lancet 2010;376:1147). In this study, a higher percentage of men in the CbzP group had grade ≥3 neutropenia (81.7% versus 58.0%). We analyzed the effect of G-CSF use on the occurrence of grade ≥3 neutropenia. Methods: 755 men with mCRPC who progressed during or after a docetaxel-containing regimen were randomized to receive 10 mg of oral prednisone daily and either 12 mg/m 2 of mitoxantrone or 25 mg/m 2 of cabazitaxel every 3 weeks. Primary prophylaxis with G-CSF was not permitted at cycle 1, but was allowed after the first occurrence of neutropenia either lasting ≥7 days or complicated by fever &gt;38.5°C, or fever &gt;38.1°C for three observations during a 24- hour period, or infection. We analyzed the effect of G-CSF use on the occurrence of neutropenia in cycles 2–10. G-CSF use was defined as either prophylactic (administered within 3 days of chemotherapy dose) or therapeutic (administered more than 3 days after chemotherapy dose). Results: A total of3246 cycles (1881 CbzP; 1365 MP) were administered from cycle 2 onward. No G-CSF was used in 2,322 cycles (1144 CbzP; 1178 MP) and the percentage of these cycles with grade ≥3 neutropenia was similar between the groups (44.6% CbzP; 38.4% MP). G-CSF was used in more cycles in the CbzP group as prophylaxis (588 CbzP; 118 MP; chi-square P&lt;0.0001) and therapeutically (149 CbzP; 69 MP; P=0.0013). The percentage of CbzP cycles with grade ≥3 neutropenia was lower when G-CSF was used early as prophylaxis versus using it later as a therapeutic modality (24.7% versus 57.7%; P&lt;0.0001). A reduction in grade ≥3 neutropenia favoring prophylactic versus therapeutic G-CSF was also observed in the MP group (9.3% versus 33.3%; P&lt;0.0001). Conclusions: The appropriate and timely use of G-CSF as prophylaxis reduces the occurrence of neutropenia in men receiving CbzP for mCRPC. Adherence to current guidelines on the use of G-CSF is recommended to manage this predictable side effect. [Table: see text]
Screening for<i>Babesia microti</i>in the U.S. Blood Supply
Authors: Erin D. Moritz, Colleen S. Winton, Laura Tonnetti, Rebecca L. Townsend, Victor P. Berardi, Mary-Ellen Hewins, Karen E. Weeks, Roger Y. Dodd, Susan L. Stramer
Journal: New England Journal of Medicine (2016)

Babesia microti, a tickborne intraerythrocytic parasite that can be transmitted by means of blood transfusion, is responsible for the majority of cases of transfusion-transmitted babesiosis in the United States. However, no licensed test exists for screening for B. microti in donated blood. We assessed data from a large-scale, investigational product-release screening and donor follow-up program.
Preliminary results of a factorial phase II randomized trial of continuous (C) or intermittent (I) docetaxel (DOC) with or without estramustine (E) as first-line treatment for castration-resistant prostate cancer (CRPC) (HOPLITE trial).
Authors: Orazio Caffo, Giovanni Lo Re, Teodoro Sava, Sebastiano Buti, Cosimo Sacco, Umberto Basso, Fable Zustovich, Thomas Martini, Alessandra Perin, Antonello Veccia, Lucianna Russo, Gaetano Facchini, Carmen Barile, Angela Gernone, Rocco De Vivo, Giovanni L. Pappagallo, Enzo Galligioni
Journal: Journal of Clinical Oncology (2012)

220 Background: DOC given for 8 consecutive courses is considered a standard first line treatment for CRPC pts and I administration could reduce its impact on quality of life (QL). E is considered synergistic with DOC. Aim of this study was to evaluate in a 2 × 2 factorial design, if I DOC could improve QL compared to C DOC and whether E added to DOC could improve its activity. Methods: CRPC pts were randomized to: C DOC 70 mg/m 2 i.v. q 3 wks for 8 courses, alone (arm A) or with E 280 mg/TID p.o. for 5 days starting on -1 day (arm B), or the same treatments given with a 3-month rest period after the first 4 courses (arm C and D, respectively). The primary end points were QL (EORTC QLQ C30 and BPI) of A+B vs C+D and 1-y PFS (according to PCWG2) of A+C vs B+D. Results: From 11/06 to 10/10, 148 CRPC pts were enrolled and 124 pts are presently evaluable (24 too early). The median age was 69 (range 42–81) and the median baseline PSA was 55.6 (range 0.33–4212). The major hematological toxicities were: anemia G3 (3 pts), neutropenia G3 (4 pts) – G4 (5 pts), febrile neutropenia (5 pts). QL outcomes of C and I groups, were not statistically different in terms of general QL items. 1-y PFS was also superimposable (10% and 13.5%, respectively) for DOC and DOC+E groups. The 2-y overall survival was also evaluated with no differences between I and C groups (42.5% and 53.7% respectively) and between DOC and DOC+E groups (42.8% and 53.5% respectively). Conclusions: These preliminary results seem to indicate that I treatment may not improve QL compared to C treatment. Moreover, the addition of E to DOC did not improve 1-y PFS of CRPC pts. Updated data with the complete sample analysis will be presented.