tbuckley/cabot-search huggingface dataset:
Selective Renal-Vein Renin Sampling in Hypertensive Patients with Segmental Renal Lesions
Authors: Morris Schambelan, Morton Glickman, Jan R. Stockigt, Edward G. Biglieri
Journal: New England Journal of Medicine (1974)

Abstract Selective intrarenal catheterization was used to obtain venous blood draining a lesion affecting only a segment of one kidney in nine hypertensive patients (four segmental infarcts, four renal-artery branch stenoses and one renin-secreting tumor). The main renal-vein renin ratio between the affected and contralateral kidneys (Ra/Rc) was > 1.5 in only four of nine patients (mean ratio ± S.E. 2.1 ± 0.5), whereas the ratio when the segmental sample (Rseg/Rc) was used was significantly higher: > 1.5 in all (4.5 ± 1.1). By contrast, neither plasma renin activity in segmental samples from normal areas of the affected kidney nor that in intrarenal samples of two patients with main renal-artery stenosis exceeded plasma renin activity of the affected kidney. Selective renal-vein renin sampling can specifically identify a localized source of renin that may be overlooked by main renal-vein sampling and facilitate the detection of patients with surgically remediable lesions. (N Engl J Med 290:1153–1157, 1974)
The Role of Sentinel Lymph Node Biopsy in the Management of Invasive Extramammary Paget'S Disease: Multi-Center, Retrospective Study of 151 Patients
Authors: Y. Fujisawa, K. Yoshino, K. Ohara, T. Kadono, T. Takenouchi, N. Hatta, H. Uhara, Y. Kiyohara, Y. Murata, S. Matsushita, T. Hayashi
Journal: Annals of Oncology (2014)
Underweight patients have higher risk of death after myocardial infarction, study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

After acute myocardial infarction (AMI) underweight patients have a higher risk of death than normal weight patients, even after adjustment for comorbidities and measures that assess cachexia and frailty, a US study has found.1

An increased risk of death among underweight patients after AMI has been observed before, but this was long thought to be from the effects of cachexia due to chronic disease and other comorbidities, not the effect of being underweight alone.

In a study published in PLOS Medicine the lead author, Emily Bucholz, and colleagues at Yale University in New Haven, Connecticut, analyzed medical records of patients enrolled from January 1994 to …
Increased fibrosis and impaired intratumoral accumulation of macromolecules in a murine model of pancreatic cancer co-administered with FGF-2
Authors: Satoshi Sakai, Caname Iwata, Hiroyoshi Y. Tanaka, Horacio Cabral, Yasuyuki Morishita, Kohei Miyazono, Mitsunobu R. Kano
Journal: Journal of Controlled Release (2016)
NMR-Based Metabolomics Analysis Reproducibly Identifies Unique Subject-Specific Profiles That Change during Peanut Oral Immunotherapy
Authors: Brian P. Vickery, Michael D. Kulis, Delisha Stewart, Wimal Pathmasiri, Deanna K. Hamilton, Susan McRitchie, Jason P. Burgess, Susan Sumner, A. Wesley Burks
Journal: Journal of Allergy and Clinical Immunology (2016)
Relationship Between Hemoglobin Levels and Quality of Life During Radiation Therapy Plus Concomitant or Sequential Chemotherapy in Patients With Cancer and Anemia Treated With Epoetin Alfa
Authors: Daniel Shasha, Pierre Cremieux, Louis Harrison
Journal: Journal of the National Comprehensive Cancer Network (2004)

This study in patients with cancer and anemia, who were receiving chemoradiation and were treated with epoetin alfa, examined the relationship between hemoglobin level and quality of life (QOL), change in hemoglobin and change in QOL, and incremental (1 g/dL) increase in hemoglobin and related incremental improvement in QOL. Data from a multicenter, open-label, prospective study of once-weekly epoetin alfa therapy in anemic cancer patients receiving chemoradiation were used to retrospectively evaluate the relationship between hemoglobin changes and QOL changes via correlation and longitudinal analyses. A sample selection correction method was used to ensure unbiased results. QOL (energy, activity, overall QOL) was measured using the Linear Analog Scale Assessment. An incremental analysis determined the greatest incremental increase in QOL associated with a 1 g/dL increase in hemoglobin level. Of the 777 patients enrolled, 464 met chemotherapy and radiotherapy eligibility criteria. Of these, 359 (77%) underwent two QOL assessments and were eligible for analysis. A nonlinear and statistically significant positive correlation was found between hemoglobin levels and Linear Analog Scale Assessment QOL scores ( r = 0.32 [energy], 0.33 [activity], and 0.29 [overall QOL]; P &lt; .0001). An incremental analysis used regression methods to characterize the changes in hemoglobin levels and QOL scores. Hemoglobin change was found to be a statistically significant determinant of QOL changes ( P &lt; .05). The greatest incremental QOL gain associated with a 1-g/dL change in hemoglobin occurred around hemoglobin 12 g/dL (range, 11–13 g/dL). A direct relationship exists between hemoglobin increases and corresponding QOL increases. Maximal incremental gain in QOL occurred when hemoglobin was approximately 12 g/dL (range, 11–13 g/dL).
Vancomycin and Priapism
Authors: John S. Czachor, Piero Garzaro, John R. Miller
Journal: New England Journal of Medicine (1998)

To the Editor: A 37-year-old man who had had severe diabetes since the age of 7, including complications of retinopathy, nephropathy, neuropathy, macroangiopathy, and microangiopathy, and who had received a cadaveric kidney–pancreas transplant three years earlier was hospitalized for acute infectious prepatellar bursitis of the left knee. Since receiving his transplant, he had taken 125 mg of cyclosporine orally twice daily, 10 mg of prednisone daily, 1 g of mycophenolate mofetil orally daily, and a single tablet of double-strength trimethoprim–sulfamethoxazole daily. Intravenous treatment with 2 g of cefazolin every eight hours and 2 g of aztreonam every eight hours was . . .
TMOD-12THE FUNCTION OF ACHAETE-SCUTE HOMOLOG 1 (ASCL1) IN GLIOBLASTOMA MULTIFORME
Authors: Tou Yia Vue, Mark Borromeo, Rahul Kollipara, Tomoyuki Mashimo, Tyler Smith, Robert Bachoo, Jane Johnson
Journal: Neuro-Oncology (2015)

Glioblastoma multiforme (GBM) are incurable brain tumors that account for the majority of high-grade gliomas in the central nervous system (CNS). Currently, therapeutic approaches targeted at genomic alterations are ineffective in stopping these tumors and prognosis for GBM patients remains poor. Interestingly, many of the genes that are upregulated in GBM are transcription factors that are normally expressed in neural progenitor or stem cells. One such factor is the proneural factor Achaete-Scute Homolog 1(ASCL1), which plays a crucial role in cell fate specification, differentiation, and progenitor cell maintenance. It is possible that the aberrant expression of ASCL1 in GBM may bestowed upon tumor cells with “stem cell-like” property and the ability to develop resistance to chemotherapy and radiation. Indeed, ASCL1 has been shown to be required for the survival of a number of lung cancers with neuroendocrine features. Yet, to date the direct contribution and requirement of ASCL1 in GBM development in vivo remains unclear. In this study, we showed that ASCL1 is expressed in early stage as well as terminal stage brain tumors of a GBM mouse model. ChIP-seq shows that ASCL1 binds to about 9,800 sites within the genome associated with genes known to regulate diverse biological processes such as those involved in neural stem cell maintenance, inhibition of neural stem cell differentiation, and cellular response to vascular endothelial growth factor (VEGF). Conditional knock-out of ASCL1 (ASCL1-CKO) significantly improved the survival time of the GBM mouse model. Uniquely, RNA-seq gene expression profiling revealed that ASCL1+ tumors of the GBM mouse model closely resemble the proneural human GBM subtype, whereas ASCL1-CKO tumors resemble that of the mesenchymal GBM subtype. Collectively, these findings demonstrate a critical role for ASCL1, a single factor, in regulating GBM development and subtype, and may serve as a potential target for therapeutic purposes.
Identical-Twin (Syngeneic) Marrow Transplantation for Hematologic Cancers&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Fefer, M A Cheever, P D Greenberg
Journal: JNCI Journal of the National Cancer Institute (1986)

The Seattle Marrow Transplant Team treated about 130 patients (age 4-68 yr) for hematologic cancer with supralethal chemoradiotherapy and bone marrow transplantation (BMT) from the normal genetically identical twin. The procedure was well tolerated. The principal problem was tumor resistance. Nevertheless, BMT for acute leukemia in relapse still cured about 20% of the patients. Moreover, BMT performed while in complete remission cured about 50% of patients with acute lymphocytic leukemia or acute nonlymphocytic leukemia. Sixteen patients received transplantation in the chronic phase of Ph1+ chronic granulocytic leukemia (CGL). All showed disappearance of all Ph1+ cells. Two died of pneumonitis. Of the 14 who are alive, 3 continue to have CGL 37-76 months after BMT and 11 remain in complete hematologic and cytogenetic remission without any Ph1+ metaphases at 31-108 months (median = 68) after BMT. Thus the Ph1-positive clone can be ablated and blast crisis prevented. BMT in the accelerated or blastic phase was far less effective. Syngeneic BMT also benefited or cured patients with lymphoma, hairy-cell leukemia, and multiple myeloma. Therefore, BMT should be considered for every patient who has a hematologic cancer and an identical twin.
Prevention of Infection in Surgical Wounds
Authors: Ralph Adams
Journal: New England Journal of Medicine (1957)

WOUND infection has become one of the most difficult surgical problems of the current decade.1 Widespread bacterial resistance and crossinfection of the hospital population have been observed repeatedly,2 , 3 and alleged by some to be penalties of indiscriminate use of antibiotics.4 , 5 Until eight months ago, it was believed at this hospital that these problems were limited to metropolitan areas and large hospitals, for only 7 infections had been encountered as complications in 1740 operations done in the preceding four years. Then, in 1955, there were 8 infections after 603 operations, 7 of which occurred within a single week. Critical review and . . .
Acute myeloid leukemia (AML) after a prior diagnosis of other hematological malignancies (HM), breast cancer (BC), and other cancers (OC) in the Australian female population between 1982 and 2002
Authors: G. Beadle, P. Baade, L. Fritschi
Journal: Journal of Clinical Oncology (2007)

7052 Background: AML is a widely reported complication of chemotherapy for HM and BC but few population based studies have investigated the nature and magnitude of AML risk after a diagnosis of cancer. Methods: This retrospective study examined 3 cohorts of female patients 30 years and over reported to state and territory cancer registries in Australia between 1982 and 2002. The cohorts comprised 40,030 women with HM, 162,142 with BC and 379,347 with OC. Results: The AML incidence rate/100,000 (IR) was 4.1 for all Australian females. The rate was much higher in the cohort with HM (IR 36.2; CI 25.3 –51.7), and slightly higher among those with BC (IR 11.7; CI 9.4 –14.9) and OC (IR 7.7; CI 6.4 –9.2). Standardized incidence ratio (SIR) estimates confirmed that women in the 3 cohorts had higher risks of subsequent AML than the general female population. These ranged from 5.5 times higher for those with HM (p &lt;0.001), 2.7 for BC (p &lt;0.001) and 1.7 for OC (p &lt;0.001). Although the IR for AML rose sharply with age, the SIR estimates for HM and BC, but not OC, were highest in the young age group and decreased with increasing age (30–49 years HM 21.6, BC 5.1; 50–69 years HM 10.4, BC 2.9; 70 years and older HM 1.8, BC 1.9; all p values &lt; 0.001). There was no evidence that time to diagnosis curves for AML were different for the 3 cohorts (53% within 5 years for HM, 60% for BC and 59% for OC). Conclusion: AML risk was higher for female cancer survivors than for the non-cancer population and was a continuing risk for long term survivors. Although the absolute risk increased with age, the relative risk was highest in young survivors of HM and BC, and decreased with age. There was no evidence of a disproportionate increase of AML risk for cancer survivors during this era of expansion of the evidence base for more extensive chemotherapy, although there was a significant increase in the risk of AML for the Australian female population. No significant financial relationships to disclose.
Temozolomide (TMZ) for progressive primitive brain tumors: safety at 75 mg/m<sup>2</sup> a day for 21 days every 28: A GICNO (Italian Neuro-Oncology Group) study
Authors: A. A. Brandes, G. Cavallo, A. Tosoni, M. Ermani, E. Franceschi, L. Scopece, C. Ghimenton, V. Blatt, L. Nicolardi, L. Crinò
Journal: Journal of Clinical Oncology (2005)

1541 Background: The activity of TMZ, at a standard schedule of 200 mg/m2 for five-days every 28, appears encouraging in patients with relapsed and newly diagnosed malignant gliomas. A continuous dose schedule of TMZ leads to DNA repair enzyme AGAT level depletion in tumor cells. AGAT, by removing TMZ-produced methyl adducts, contributes to the development of resistance to alkylating agents. The aim of the present study was therefore to determine the safety of continuous low-dose TMZ administration. Methods: From November 2003 to October 2004, 55 patients (34 male; mean age 52, range 28–71 years) with progressive brain tumors had oral TMZ 75 mg/m2 for 21 consecutive days, every 28. Forty-six pts (83.6%) had prior RT; 46 were chemo-naïve. Results: A total of 237 (median 4; range, 1–13) cycles were delivered. G2 and G3 toxicity were: lymphopenia, 27.5 and 17.6%; neutropenia, 1.9 and 3.9%; thrombocytopenia, 5.9% and 0; nausea, 3.6 and 3.6%; hepatic 3.6 and 1.8%, respectively. Two patients (3.6%) had reversible renal toxicity G1, and one, (1.8%) G2; one (1.8%) had prolonged G4 neutropenia; none had pneumocisti carinii pneumonia. TMZ was discontinued in 1 case (1.8%) due to G2 skin allergy. Seven (12.7%) patients converted to standard schedule TMZ: 1 had G2 renal toxicity which resolved and did not recur with standard schedule TMZ; 2, prolonged G2 thrombocytopenia and G3 neutropenia, respectively; 4 refused to continue with the continuous schedule. Conclusions: Continuous low-dose TMZ has an acceptable safety profile, but can incur renal reversible G1-G2 toxicity and cumulative lymphopenia. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough
Agents Make “Preferred List” in Metastatic Melanoma
Authors: John A. Thompson
Journal: Journal of the National Comprehensive Cancer Network (2014)

The 2014 version of the NCCN Guidelines for Melanoma lists 6 preferred regimens, most with a category 1 recommendation, and 8 "other active regimens." Effective new agents include ipilimumab, a monoclonal anti-CTLA4 antibody, and agents targeted against mutated BRAF and MEK. Researchers are now focused on the optimal way to combine or sequence these agents, while exploring other new classes.
Case 12-2016
Authors: Madhusmita Misra, Pallavi Sagar, Alison M. Friedmann, Daniel P. Ryan, Dennis C. Sgroi
Journal: New England Journal of Medicine (2016)

An 8-year-old boy presented with a mass in the right breast that had been present for 18 months and had enlarged during the previous 6 months. On examination, a firm, mobile mass (2 cm by 2 cm) was present under the right areola. Diagnostic procedures were performed.
Azacitidine front-line in 339 patients with myelodysplastic syndromes and acute myeloid leukaemia: comparison of French-American-British and World Health Organization classifications
Authors: Lisa Pleyer, Sonja Burgstaller, Reinhard Stauder, Michael Girschikofsky, Heinz Sill, Konstantin Schlick, Josef Thaler, Britta Halter, Sigrid Machherndl-Spandl, Armin Zebisch, Angelika Pichler, Michael Pfeilstöcker, Eva-Maria Autzinger, Alois Lang, Klaus Geissler, Daniela Voskova, Dietmar Geissler, Wolfgang R. Sperr, Sabine Hojas, Inga M. Rogulj, Johannes Andel, Richard Greil
Journal: Journal of Hematology & Oncology (2016)

The MDS-IWG and NCCN currently endorse both FAB and WHO classifications of MDS and AML, thus allowing patients with 20-30 % bone marrow blasts (AML20-30, formerly MDS-RAEB-t) to be categorised and treated as either MDS or AML. In addition, an artificial distinction between AML20-30 and AML30+ was made by regulatory agencies by initially restricting approval of azacitidine to AML20-30. Thus, uncertainty prevails regarding the diagnosis, prognosis and optimal treatment timing and strategy for patients with AML20-30. Here, we aim to provide clarification for patients treated with azacitidine front-line.The Austrian Azacitidine Registry is a multicentre database (ClinicalTrials.gov: NCT01595295). For this analysis, we selected 339 patients treated with azacitidine front-line. According to the WHO classification 53, 96 and 190 patients had MDS-RAEB-I, MDS-RAEB-II and AML (AML20-30: n = 79; AML30+: n = 111), respectively. According to the FAB classification, 131, 101 and 111 patients had MDS-RAEB, MDS-RAEB-t and AML, respectively.The median ages of patients with MDS and AML were 72 (range 37-87) and 77 (range 23-93) years, respectively. Overall, 80 % of classifiable patients (≤30 % bone marrow blasts) had intermediate-2 or high-risk IPSS scores. Most other baseline, treatment and response characteristics were similar between patients diagnosed with MDS or AML. WHO-classified patients with AML20-30 had significantly worse OS than patients with MDS-RAEB-II (13.1 vs 18.9 months; p = 0.010), but similar OS to patients with AML30+ (10.9 vs 13.1 months; p = 0.238). AML patients that showed MDS-related features did not have worse outcomes compared with patients who did not (13.2 vs 8.9 months; p = 0.104). FAB-classified patients with MDS-RAEB-t had similar survival to patients with AML30+ (12.8 vs 10.9 months; p = 0.376), but significantly worse OS than patients with MDS-RAEB (10.9 vs 24.4 months; p < 0.001).Our data demonstrate the validity of the WHO classification of MDS and AML, and its superiority over the former FAB classification, for patients treated with azacitidine front-line. Neither bone marrow blast count nor presence of MDS-related features had an adverse prognostic impact on survival. Patients with AML20-30 should therefore be regarded as having 'true AML' and in our opinion treatment should be initiated without delay.
Bevacizumab (BV) related adverse events among various age groups of elderly patients with advanced colorectal cancer
Authors: A. K. Raman, J. C. Lombardo, R. Chandrasekhar, M. G. Fakih
Journal: Journal of Clinical Oncology (2007)

14546 Background: Hypertension (HTN), arterial thrombosis (ATE), venous thrombosis (VTE), and gastrointestinal perforation (P) are known BV related adverse events. The incidence of these events in different age groups of elderly patients (= 65 years) has not been well described. This study aimed at identifying the incidence of HTN, ATE, VTE, and P among three age groups: 65–69, 70–74 and =75 years. Methods: A retrospective chart review of CRC patients = 65 yrs treated with BV based chemotherapy during the period of January 2004 - July 2006 at Roswell Park Cancer Institute was performed. The incidence of grade (G) 3–4 HTN, ATE, VTE, and P was calculated. Results: Sixty patients = 65 yrs received BV during the study period: 20 patients were 65–69, 19 were 70–74, and 21 were = 75 years of age. The median age was 73 (range 65–90). Eight (13.3%) patients developed G3–4 arterial thromboembolic events, 7 (11.6%) developed G3–4 venous thromboembolic events, 10 (16.6%) developed G3 HTN, and 2 (3.3%) had a bowel perforation. The incidence of ATE was the highest in the = 75 age group (4/21, 19%) when compared to the 70–74 age group (2/19, 11%) and the 65–69 age group (2/20, 10%). Similarly, G3 HTN was more common in the = 75 years age group (6/21, 29%) when comparison to the 70–74 (2/19, 11%) and the 65–69 (2/20, 10%) age groups. VTE were evenly distributed in all 3 age groups while one P occurred in the 70–74 and = 75 age groups respectively. The trend of increasing incidence of ATE and HTN did not reach statistical significance using Odds Ratio analysis (SAS exact logistic regression method), likely due to the small sample size. Conclusion: The incidence of ATE and HTN is increased in the elderly population, especially in patients = 75 yrs. BV based therapy needs to be investigated further in this population to determine if BV clinical benefits outweigh the associated risks. No significant financial relationships to disclose.
A phase II study of YM155, a novel survivin suppressant, administered by 168 hour continuous infusion in patients with unresectable stage III or stage IV melanoma
Authors: R. Gonzalez, K. Lewis, W. Samlowski, L. Cranmer, J. Catlett, J. Kirkwood, E. Whitman, D. Lawson, P. Bartels, T. Drake
Journal: Journal of Clinical Oncology (2007)

8538 Background: In cell line studies, YM155 showed markedly potent antiproliferative activity against melanoma with 50% growth inhibition (GI 50 ) values ranging from 0.35 nM to 910 nM. In melanoma tumor-bearing mouse xenograft models, YM155 showed significant antitumor activity including regression of tumors, at doses ranging from 1 to 10 mg/kg/day. Methods: Chemotherapy naive patients with unresectable Stage III or IV melanoma were eligible. The primary endpoint was tumor response defined by RECIST criteria. Secondary endpoints included progression-free survival and toxicity. A Simon's two stage minimax design was utilized with the first stage requiring 1 response (N=27) and a total of 2 responses required at the conclusion of stage II (N=29). Patients were considered evaluable if they completed 2 cycles. YM155 was given as a 168-hour (7-day) continuous infusion every three weeks (1 cycle) at a dose of 4.8 mg/m 2 /day. Results: Enrollment is complete at 34 pts in order to reach 29 evaluable with treatment ongoing. Results are available for the first 26 pts. Median age was 59 y/o, (range 29 - 88) with ECOG PS of 0–1. There is one objective response of intrabdominal lymph nodes based on Investigator assessment at Cycle 2 confirmed at Cycle 4; another patient had a minor response (24% reduction) at Cycle 6 (currently at Cycle 8). Two subjects have shown stable disease after 6 cycles and remain on study. The median number of cycles is 3 (range 1 - 9). Two of 26 pts reported a grade 3 AE considered possibly related to YM155 (chest pain - nos and catheter related thrombosis). Nineteen of 26 pts have discontinued the study (18 PD, 1 withdrew consent). Conclusions: YM155 induced responses in 2 pts and was generally well tolerated. Given this encouraging response as a single agent, studies of YM155 combined with other agents are under consideration. [Table: see text]
Reconstitution of Hematopoiesis after High-Dose Chemotherapy by Autologous Progenitor Cells Generated ex Vivo
Authors: Wolfram Brugger, Shelly Heimfeld, Ronald J. Berenson, Roland Mertelsmann, Lothar Kanz
Journal: New England Journal of Medicine (1995)

Autologous peripheral-blood progenitor cells can restore hematopoiesis after high-dose chemotherapy in patients with solid tumors or hematologic cancers. We investigated the ability of peripheral-blood progenitor cells generated ex vivo to restore hematopoiesis in patients with cancer who have undergone high-dose chemotherapy.