tbuckley/cabot-search huggingface dataset:
Acute changes in physiological parameters and pulmonary function during and after fibreoptic bronchoscopy
Authors: Anant Mohan, Randeep Guleria, Ashraf Ali, Ajit Kumar
Journal: European Respiratory Journal (2011)

Background: The short term effects of fibreoptic bronchoscopy (FOB) on physiological and pulmonary function parameters are not well known.

Method: Pulmonary function test was performed in patients before and within 30 minutes after bronchoscopy. Heart rate, blood pressure and oxygen saturation were recorded at the start of procedure and 5 and 10 minutes later.

Results: 55 patients were studied [39 males, mean (SD) age, 45.89 (13.77) years]. Mean (SD) BMI was 21.3 (3.82). 76.4% patients were non smokers and 16.4% were current smokers. Most patients were being evaluated for suspected carcinoma lung (27.3%), pneumonia (14.5%), interstitial lung disease (9.1%), Mediastinal lymphadenopathy (9.1%), carcinoma esophagus (7.3%) and fibrocavitary lesions (7.3%). The commonest complaints were cough (45.5%), shortness of breath (30.9), chest pain (12.7%), wheezing (7.3%), hoarseness of voice (7.3%), Hemoptysis (1.8%) and fever (1.8%). During the procedure there was significant increase in heart rate, systolic blood pressure and diastolic blood pressure while oxygen saturation declined. Post procedure there was a significant decline in FEV1, FVC, PEFR and FEF25-75 (Table).

View this table:

Table 1. Changes in pulmonary function before and after bronchoscopy





Conclusion: Bronchoscopy causes a significant acute decline in pulmonary functions. There may be thus, a justification for prophylactic use of inhaled bronchodilators prior to performing bronchoscopy.
Cetuximab reversal of resistance to chronomodulated chemotherapy in heavily-pretreated patients with metastatic colorectal cancer (MCC) without amplification of epidermal growth factor receptor (EGFR) gene
Authors: F. A. Lévi, A. Karaboué, M. Bralet, P. Innominato, M. O. Herelle, S. Giacchetti, R. Adam, C. Jasmin, C. Guettier, M. Bouchahda
Journal: Journal of Clinical Oncology (2006)

13104 Background Skin toxicity and EGFR amplification reportedly predicted for Cetux-reversal of MCC resistance to standard chemotherapy. We explored these relations for Cetux reversal of resistance to chronomodulated chemotherapy (Chrono) with irinotecan (CPT11, peak at 5 am), 5-fluorouracil-leucovorin (FU-LV, peak at 4 am) and oxaliplatin (l-OHP, peak at 4 pm). Methods: 40 pts with progressive MCC on 3 prior chemotherapy lines received weekly Cetux (250 mg/m 2 ) and q2–3 wks CPT11-based (30 pts) or oxaliplatin-based (10 pts) Chrono. Toxicities and response were assessed q2–3 wks and q2 months (mo) respectively. Tumor EGFR expression was determined by immunohistochemistry for all pts and gene copies by fluorescent in situ hybridization (FISH) for 25 pts. Results: All pts had prior progression on CPT11, FU-LV and l-OHP. Median age: 61 yo; M/F: 24/16; WHO PS 0/1/2: 27/9/4; colon/rectum: 21/19; M sites 1/2/≥ 3: 12/15/13; liver/lung: 32/29; pre-existing peripheral sensory neuropathy grade ≥ 2: 11 pts. A median of 8 courses of Cetux-Chrono was given (1 to 22). Three pts withdrew for grade 4 allergy. 37 pts were assessable for other toxicities and 36 for response (1 too early). Gr 2–3 acneiform skin rash occurred in 27 pts (73%), with gr3 in 11 pts (29.7%). Other main gr 3–4 toxicities were diarrhea (27% of the pts), neutropenia (24.3%) and neuropathy (21.6%). Disease progressed in 12 pts (33.3%) and was controlled in 24 pts (66.7%) including 13 stable disease (36.1%) and 10 objective responses (8 PR and 2 CR) - 27.8% [95% C.L. 12.9 to 42.7]. EGFR was expressed in 32 pts (80%), with &gt;10% + tumor cells for 14 pts (35%). 3/6 EGFR- pts (50%) and 7/32 EGFR+ pts (21.9%) responded. No gene amplification was documented in the 25 tumors (7 responders). A positive correlation between skin rash and disease control was suggested (p from χ 2 = 0.08). Median progression free and overall survival (mo) are 5.3 [2.9–8.4] and 11.1 [8.6–13.6] respectively. Conclusions: Cetux partly alleviated MCC resistance to Chrono, independently of tumor EGFR protein expression or gene amplification, possibly through interfering with TGFα. This EGFR ligand carries poor prognosis for MCC and alters circadian clock function. [Table: see text]
Late Effects of Low-Dose Adjuvant Chemotherapy in Colorectal Cancer
Authors: John D. Boice
 3, Mark H. Greene, Robert J. Keehn, George A. Higgins, Joseph F. Fraumeni, Jr.
Journal: JNCI Journal of the National Cancer Institute (1980)

As part of a systematic program to evaluate the late effects of antineoplastic therapy in randomized clinical trials, patients enrolled in the low-dose thio-TEPA (TSPA) and 5-fluoro-2'-deoxyuridine (FdUrd) adjuvant colorectal cancer protocols of the Veterans Administration (VA) Surgical Oncology Group between 1958 and 1964 were studied. All patients received surgery with curative intent; 470 also received TSPA, 176 received FdUrd, and 867 received surgery only. The unique VA system permitted complete follow-up through 1977, with 10,902 person-years of observation accrued among 1,613 male patients (mean survival = 6.8 yr). Expected mortality and cancer incidence were computed by applying U.S. Mortality Statistics and Connecticut Tumor Registry age-, race-, sex-, and calendar time-specific rates to the person-years of observation. The mortality experience of the 3 groups was similar. Overall, there was a significant excess in total mortality (observed/expected = 1,359/553) attributable mainly to colorectal cancer (584/14), arteriosclerotic heart disease (258/215.9), pneumonia (41/17), gastric and duodenal ulcers (15/4), and cirrhosis (14/6). No excess mortality from noncolorectal cancers was apparent, nor were there significant differences by treatment: TSPA (22/22), FdUrd (9/12), and surgery only (50/42). Among 1,402 white patients, no significant excess of incident noncolorectal cancers were observed among patients treated with TSPA (30/31, FdUrd (14/15), or surgery only (63/58). Seven incident cases of leukemia developed (4.1 expected) among all patients of various groups: TSPA (3/1.3), FdUrd (1/0.6), and surgery only (3/2.2). No excess of new primary cancers was observed among 211 nonwhite patients. An inverse relationship between the occurrence of second primary cancer and age at diagnosis, irrespective of therapy, was suggested. The results demonstrated the feasibility of this approach for assessment of late complications of anticancer therapy and suggested no measurable carcinogenic effect following very low doses of TSPA and FdUrd in a population of this size.
Choice of immunosuppressant should be reviewed in patients who develop diabetes after transplantation.
Authors: David Spurgeon
Journal: BMJ (2003)

A panel of experts from Europe, the United States, and Canada have published the first international consensus guidelines on the diagnosis, treatment, and management of new onset diabetes after transplantation, which affects up to 53% of transplant patients (Transplantation 2003;75:S1-22). The condition increases the risk of organ rejection, organ loss, and infections by as much as 63% and the risk of death by 87%.

As transplantation has become more successful in terms of survival of patients and of grafts, the management of complications has become more important. The risk of cardiovascular complications among transplant patients is 6.4 times the risk in the healthy population. New onset diabetes after transplantation increases this risk to 20 times.

The condition is underdiagnosed because of a lack of consensus in defining it. The commonest definition—a requirement for insulin treatment—fails to take account of patients with impaired glucose tolerance who are treated with diet and exercise and patients treated with oral drugs.

The new guidelines recommend adopting the definitions most recently proposed by the World Health Organization, the American Diabetes Association, the International Diabetes Federation, and the American College of Endocrinology.

The guidelines say that risk factors associated with new onset diabetes after transplantation include a family history of diabetes; being from a particular ethnic group (among US patients, black and Hispanic people are more predisposed), greater age, greater body weight, and previous hepatitis C infection.

The main modifiable risk factors are body weight and immunosuppression treatment. Measures that should be taken to reduce the risk of cardiovascular complications include a low fat diet, lipid lowering drugs, tighter glycaemic control, and blood pressure control.

The most common immunosuppressing drugs are ciclosporin and other corticosteroids, such as tacrolimus. A meta-analysis of studies that compared the incidence of new onset diabetes after transplantation showed a fivefold higher incidence of the condition in patients treated with tacrolimus than in patients treated with ciclosporin. And a recent study using Medicare data showed the incidence of new onset diabetes to be about 70% higher in patients treated with tacrolimus than in patients treated with ciclosporin.

Professor Alan Wilkinson, director of the kidney and pancreas transplant programmes at the University of California at Los Angeles and co-chairman of the expert panel, said: I strongly urge transplant clinicians to adopt the management strategies that these guidelines recommend.
MEK inhibitor, TAK-733 reduces proliferation, affects cell cycle and apoptosis, and synergizes with other targeted therapies in multiple myeloma
Authors: P de la Puente, B Muz, A Jin, F Azab, M Luderer, N N Salama, A K Azab
Journal: Blood Cancer Journal (2016)

MEK inhibitor, TAK-733 reduces proliferation, affects cell cycle and apoptosis, and synergizes with other targeted therapies in multiple myeloma
Double depression and episodic major depression: demographic, clinical, familial, personality, and socioenvironmental characteristics and short- term outcome
Authors: D N Klein, E B Taylor, K Harding, S Dickstein
Journal: American Journal of Psychiatry (1988)

The authors compared 31 outpatients with double depression to 50 outpatients with episodic major depression. Patients with double depression exhibited significantly greater impairment, more severe depressive symptoms, greater comorbidity, more personality disturbance, lower levels of social support, more chronic strains, and higher rates of bipolar II and nonbipolar affective disorders in first-degree relatives. In addition, in a 6-month follow-up, the patients with double depression were significantly less likely to recover, and a higher proportion experienced hypomanic episodes than did patients with episodic major depression. These data provide strong support for the clinical significance of double depression.
Pathology concordance levels for meningioma classification and grading in NRG Oncology RTOG Trial 0539
Authors: C Leland Rogers, Arie Perry, Stephanie Pugh, Michael A Vogelbaum, David Brachman, William McMillan, Joseph Jenrette, Igor Barani, Dennis Shrieve, Andy Sloan, Joseph Bovi, Young Kwok, Stuart H Burri, Samuel T Chao, Aaron C Spalding, Mitchell S Anscher, Beatrice Bloom, Minesh Mehta
Journal: Neuro-Oncology (2015)

With advances in the understanding of histopathology on outcome, accurate meningioma grading becomes critical and drives treatment selection. The 2000 and 2007 WHO schema greatly increased the proportion of grade II meningiomas. Although associations with progression-free survival (PFS) and overall survival (OS) have been independently validated, interobserver concordance has not been formally assessed. Once mature, NRG Oncology RTOG-0539 will report PFS and OS in variably treated low-, intermediate-, and high-risk cohorts. We address concordance of histopathologic assessment between enrolling institutions and central review, performed by a single pathologist (AP), who is also involved in developing current WHO criteria. The trial included 170 evaluable patients, 2 of whom had 2 eligible pathology reviews from different surgeries, resulting in 172 cases for analysis. Upon central review, 76 cases were categorized as WHO grade I, 71 as grade II, and 25 as grade III. Concordance for tumor grade was 87.2%. Among patients with WHO grades I, II, and III meningioma, respective concordance rates were 93.0%, 87.8%, and 93.6% (P values < .0001). Moderate to substantial agreement was encountered for individual grading criteria and were highest for brain invasion, ≥20 mitoses/10 high-powered field [HPF], and spontaneous necrosis, and lowest for small cells, sheeting, and ≥4 mitoses/10 HPF. In comparison, published concordance for gliomas in clinical trials have ranged from 8%–74%. Our data suggest that current meningioma classification and grading are at least as objective and reproducible as for gliomas. Nevertheless, reproducibility remains suboptimal. Further improvements may be anticipated with education and clarification of subjective criteria, although development of biomarkers may be the most promising strategy.
Central nervous system (CNS) leukemia after imatinib mesylate therapy for chronic myelogenous leukemia (CML)
Authors: M. M. Solh, H. Kantarjian, S. O'Brien, F. Giles, S. Faderl, G. Garcia-Manero, M. Rios, J. Shan, J. Cortes, F. Ravandi-Kashani
Journal: Journal of Clinical Oncology (2007)

7042 Background: Imatinib is the standard first line treatment for CML. Imatinib penetrates the CSF poorly. We examined the incidence and outcome of CNS disease in pts with CML treated with imatinib at our institution. Methods: The clinical data for pts with early or late chronic phase and accelerated phase CML treated with imatinib between 1999 and 2006 were reviewed. Pts who were started on imatinib elsewhere and progressed to blast phase were also included. CNS disease was defined as a pathologically proven enhancing lesion (leptomeningeal or parenchymal) or presence of CSF leukemic cells. Results: Nine hundred and ten pts with chronic or accelerated phase CML were treated with imatinib. Fifty five developed blast crisis while on imatinib; another 28 pts had blast transformation while receiving imatinib elsewhere, making up a total of 83 pts. At diagnosis, their median age was 51 yrs, median Hgb, WBC and PLT counts were 10.6 g/dl, 59.7×10 9 /L and 307×10 9 /L, respectively. Median time from diagnosis to starting imatinib was 45.4 mts and the median duration of imatinib therapy was 17.9 mts. Fifteen pts had achieved a complete cytogenetic response and 47 had a complete hematologic response before progressing to blast phase. Their median overall survival from diagnosis was 73.2 mts. Thirty pts developed extramedullary disease; they had similar baseline characteristics as the rest with a median survival of 68.3 mts. Fifteen pts developed CNS disease (5 leptomenigeal, 5 CSF, 3 parenchymal, and 2 spinal cord); 14 had concomitant medullary blast crisis. They had a statistically significant younger age at diagnosis (41.9 vs 52.4 yrs), lower platelet counts (186 vs 334×10 9 /L), and shorter overall survival (66.7 vs 73.2 mts) compared to the other pts with blast phase. Conclusions: CNS disease occurs infrequently in pts receiving imatinib for CML but should be suspected in pts with relevant symptoms. Pts developing CNS leukemia had a worse prognosis; this may be secondary to an inherently worse disease, poor CSF penetration of imatinib, and subsequent difficulty in eradicating CNS disease using available therapies. More potent tyrosine kinase inhibitors, such as nilotinib and dasatinib, and new agents with the ability to cross the blood-brain barrier should be evaluated in this setting. No significant financial relationships to disclose.
Phylogenetic relationships and unusual diversity in histone H4 proteins within the Tetrahymena pyriformis complex.
Authors: L A Sadler, C F Brunk
Journal: Molecular Biology and Evolution (1992)

The 29 species of the Tetrahymena pyriformis complex are morphologically identical while being quite diverse at the molecular level. These species are also diverse relative to other eukaryotes. Phylogenetic relationships within the complex have been difficult to determine, because there are groups of closely related species, as well as individual species, that are highly divergent. We have sequenced portions of two highly conserved histone genes and the more rapidly evolving intergenic region between them. These sequences have been used to construct a phylogeny for the complex. A comparison of the amino-terminal portion of the histone H4 proteins from the species of the complex reveals a high degree of sequence diversity relative to that of other organisms. In contrast, the amino-terminal portions of the histone H3 proteins of the species in the complex are identical to each other. We also find that the pattern of nucleotide substitution in the intergenic region differs from that described for higher eukaryotes.
Histone-Associated Thrombocytopenia in Patients Who Are Critically Ill
Authors: Yasir Alhamdi, Simon T. Abrams, Steven Lane, Guozheng Wang, Cheng-Hock Toh
Journal: JAMA (2016)

Histone-Associated Thrombocytopenia in Patients Who Are Critically Ill c P values are presented for thrombocytopenia group (total) vs control group with no thrombocytopenia (total).d Statistical significance determined by Mann-Whitney U test. e Percentages are calculated as [number of patients in a particular diagnosis/56 (total number of patients) × 100].
The Growth &lt;italic&gt;in Vitro&lt;/italic&gt; of Massive Cultures of Liver Cells
Authors: V J EVANS, W R EARLE, E P WILSON, H K WALTZ, C J MACKEY
Journal: JNCI Journal of the National Cancer Institute (1952)

The Growth in Vitro of Massive Cultures of Liver Cells Get access Virginia J. Evans, Virginia J. Evans Tissue Culture Unit, Laboratory of Biology, National Cancer Institute2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Wilton R. Earle, Wilton R. Earle Tissue Culture Unit, Laboratory of Biology, National Cancer Institute2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth P. Wilson, Elizabeth P. Wilson Tissue Culture Unit, Laboratory of Biology, National Cancer Institute2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Helen K. Waltz, Helen K. Waltz Tissue Culture Unit, Laboratory of Biology, National Cancer Institute2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Constance J. Mackey Constance J. Mackey Tissue Culture Unit, Laboratory of Biology, National Cancer Institute2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 6, June 1952, Pages 1245–1265, https://doi.org/10.1093/jnci/12.6.1245 Published: 01 June 1952 Article history Received: 11 February 1952 Published: 01 June 1952
Sorafenib (SOR) plus chemotherapy (CRx) for patients (pts) with advanced (adv) breast cancer (BC) previously treated with bevacizumab (BEV).
Authors: C. Hudis, K. W. Tauer, R. C. Hermann, G. Makari-Judson, C. Isaacs, J. T. Beck, V. G. Kaklamani, E. J. Stepanski, H. S. Rugo, W. Wang, K. M. Bell-McGuinn, H. Chera, B. Zaugg, S. K. Ro, S. Li, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2011)

1009 Background: SOR, a multikinase inhibitor targeting tumor growth and angiogenesis, is indicated for adv renal and hepatocellular cancer. The Trials to Investigate the Efficacy of SOR (TIES) program is four double-blind, randomized, placebo (PL)-controlled, phase IIb screening trials assessing SOR+CRx for HER2-negative locally adv or metastatic (met) BC. Two TIES studies (SOLTI-0701, NU07B1) reported activity for SOR+CRx vs PL+CRx in pts with no prior BEV. As inhibition of receptor tyrosine kinase activity may overcome BEV resistance, we conducted AC01B07, a TIES study in pts with progression on/after BEV. Methods: Pts were randomized to CRx +SOR (400 mg po twice daily [BID]) or +PL. The only CRx initially used was gemcitabine (GEM 1000 mg/m2 IV, days 1, 8 of 21) but later capecitabine (CAP 1,000 mg/m2 po BID, days 1−14 of 21) was added as an alternative at the physician’s discretion. The primary endpoint was progression-free survival (PFS). Planned sample size was 160 pts with analysis after 120 PFS events (1-sided α=.14). With 120 events, an observed hazard ratio (HR) of 0.70 corresponds to 1-sided false positive error of .025. Results: As expected, more pts received GEM than CAP. SOR was associated with statistically significant improvements in PFS and time to progression (TTP). Hand-foot skin reaction/syndrome (HFSR/HFS) was the most common G3/4 adverse event (AE) with SOR+CRx. Conclusions: The addition of SOR to CRx provided a PFS benefit in pts with previous BEV tx. These results are consistent with other TIES studies and support a potential role for SOR+CRx in adv BC even after BEV tx. Findings will need to be confirmed in a phase III trial. SOR+CRx N=81 PL+CRx N=79 CRx GEM, % 83 82 CAP, % 17 18 Baseline characteristics Age, mean, y 53.5 54.2 AJCC stage IV, % 95 95 Met sites, % Visceral 85 84 No. >3 20 25 Prior non-met tx, % BEV 3 1 CRx 81 67 Taxane 43 47 Anthracycline 51 49 Prior met tx, % BEV 96 99 CRx 94 96 Taxane 64 61 Anthracycline 0 3 Efficacy PFS, median, mo 3.4 2.7 HR (95% CI) 0.65 (0.45, 0.95) 1-sided p .01 TTP, median, mo 3.6 2.7 HR (95% CI) 0.64 (0.44, 0.93) 1-sided p .009 Overall response, % 19.8 12.7 1-sided p .12 Overall survival Pending AEs Tx-emergent G3/4, % 87 64 HFSR/HFS 39 5 Neutropenia 21 27 Stomatitis 10 0
Effect of the combination of pegylated liposomal doxorubicin and bortezomib on time to progression (TTP) and overall survival of patients with relapsed/refractory multiple myeloma compared with bortezomib alone
Authors: J. L. Harousseau, A. Nagler, P. Sonneveld, J. Bladé, R. Hajek, A. Spencer, T. Robak, L. Xiu, S. H. Zhuang, R. Z. Orlowski
Journal: Journal of Clinical Oncology (2007)

8002 Background: Proteasome inhibition with bortezomib is a standard of care for patients with relapsed/refractory multiple myeloma (MM). Recently, we reported the results of an interim analysis for the DOXIL-MMY-3001 study, a large multi-national, phase III, randomized study of patients with previously treated MM demonstrating that the combination of pegylated liposomal doxorubicin (PLD) and bortezomib resulted in a 45% risk reduction of experiencing disease progression over bortezomib alone (Orlowski et al, 2006 ASH Meeting, Abstract #404). The improvement in TTP was associated with an overall survival (OS) trend favoring the combination therapy (P=0.113; hazard ratio[HR], 1.48, 95% Confidence Interval [CI], 0.91 to 2.41). We now present an updated survival analysis with a median follow up of 11 months. Methods: 646 patients at 123 centers in 18 countries received either intravenous bortezomib, 1.3 mg/m 2 , on days 1, 4, 8, and 11 of every 21-day cycle, or the same bortezomib regimen with PLD, 30 mg/m 2 , on day 4. Results: As previously reported, median TTP was improved from 6.5 months for bortezomib alone to 9.3 months for the PLD+bortezomib combination (P=0.000004; HR, 1.82; 95% CI, 1.41 to 2.35). The complete+partial response rate was 43% for bortezomib and 48% for PLD+bortezomib (P=0.251). Median duration of response was increased from 7.0 months (95% CI, 5.9 to 8.3) to 10.2 months (95% CI, 10.2 to 12.9) with combination therapy (p=0.0008). Updated OS analysis showed PLD+bortezomib significantly improved OS (p&lt;0.05; HR, 1.41, 95% CI, 1.002 to1.97). Both groups received a median of 5 cycles of treatment. The safety profile of the combination was consistent with the known toxicities of the two agents. Grade 3/4 adverse events were more frequent in the combination group primarily due to increase in myelosuppression and GI toxicities. Conclusions: PLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed/refractory MM. [Table: see text]