tbuckley/cabot-search huggingface dataset:
Outcome of patients less than 55 years of age with high-risk acute leukemia who did not have an HLA-identical related donor: A long-term study of 97 consecutive patients
Authors: I. Yakoub-Agha, J. Cornillon, S. Depil, F. Bauters, J. P. Jouet, P. Fenaux
Journal: Journal of Clinical Oncology (2004)

6636 Background: In this analysis, our main objectives were (1) to study the probability and the time needed to find a suitable unrelated donor or cord blood (2) to evaluate the impact of the time from the unrelated donor search (UDS) initiation to positive result on patient outcome (3) to compare the survival of pts who underwent allo-SCT with the outcome of those who received other treatments. Patients: between Jan 93 and Dec 00, an UDS was initiated for 97 consecutive pts with high-risk acute leukemia (HR-AL) (46 ALL and 51 AML). AL was considered of poor prognosis because of relapsed or refractory disease (n=70), unfavorable cytogenetic abnormalities (n=22), secondary AML (n=2) miscellaneous (n=3). The median age was 25 yrs. Sex ratio was 1,6. All pts had received previously various CT and 9 had received in addition an auto-SCT. Results: The median time to identify a suitable living donor or cord blood was 60 days. After the UDS initiation, 33 pts received unrelated allo-SCT (including 9 CB), 12 an auto-SCT, 36 CT and 13 palliative treatment. At a median of 54 months after initiation of the UDS, 18 pts were alive including 15 in CR. 79 pts died of disease progression, TRM and toxicity of intensive CT. The estimated 4-year overall survival rates were 32% for allo-SCT recipients, 37% for auto-SCT and 15% and 0% for pts receiving intensive CT and palliative treatment, respectively. Thus, pts who received, after UDS initiation, either allo- or auto-SCT had better survival than those who received other treatments including high-dose CT and palliative treatment (p<.0001). Pts who received allo-SCT died less often of relapse than pts who received other treatments (p<.0001). Conclusion: This study shows that unrelated allo-SCT gives a substantial long-term survival in pts with HR-AL. Pts who achieve CR might be good candidates for auto-SCT while waiting a donor becomes available. In pts who fail to enter into CR, iterative high-dose CT seems to have limited effects as well as palliative treatment. Finally, in absence of “gold standard” salvage therapy, refractory pts with HR-AL should be considered for clinical trials. No significant financial relationships to disclose.
Inactivation of human keratin genes: the spectrum of mutations in the sequence of an acidic keratin pseudogene.
Authors: E S Savtchenko, I M Freedberg, I Y Choi, M Blumenberg
Journal: Molecular Biology and Evolution (1988)

Keratins are cytoskeletal proteins encoded by a multigene family. We have identified the first human keratin pseudogene and determined its complete nucleotide sequence. Sequence comparisons indicate that the pseudogene arose from a very recent duplication of the 50-kd keratin (K14) gene. The coding and the intron sequences of the two genes are 95% and 93% identical, respectively. Although the sequence of the regulatory region in the pseudogene is virtually identical to that in the 50-kd functional gene, several deleterious mutations have been identified in the pseudogene. There are three frameshifts in the coding regions, one of which is a perfect 8-bp duplication. A single-base-pair deletion in the first exon and a single-base-pair insertion in the penultimate exon also result in frameshifts. The three remaining deleterious mutations interfere with the mRNA processing signals: two alter the intron/exon boundaries, and the third disrupts the polyadenylation signal. These mutations clearly identify the sequence as a human keratin pseudogene.
A multistep randomized phase II/III trial comparing oxaliplatin (OXA)+5 fluorouracil (FU) to vinorelbine (VIN)+FU (FUN) after taxane (T)/anthracycline (A) failure in advanced/metastatic breast cancer (MBC) patients (pts): Final results
Authors: S. Delaloge, M. Tubiana-Hulin, A. Wardley, L. Del Mastro, A. Santoro, A. Zambelli, A. Bonetti, C. Boni, F. Habib, S. Brienza
Journal: Journal of Clinical Oncology (2004)

660 Background: OXA is a new DACH platinum (Pt) with preclinical evidence of activity in vivo and in mammary cell lines. Previous clinical study has shown promising activity both for OXA alone (Ann Oncol 2001 Feb 12(2):179–82) and with FU (JCO 2002 15;20:2551–8) in pretreated MBC. Methods: In order to compare tolerance and activity of OXA/FU to reference regimen FUN in pts pretreated with both T and A, we conduct a randomized phase II-III trial. Pts are assigned either to OXA 130 mg/m2 2 hours IV on day (D) 1 plus FU 750 mg/m2 daily by continuous IV infusion D1 to D5 q 3 wks or VIN 25 mg/m2 IV bolus plus the same FU. Eligibility criteria included relapsing progressive MBC, at least one previous chemotherapy (CT) for MBC, no more than 3 prior CT, previous A, previous T therapy given for MBC in an appropriate dose and schedule, at least one measurable target lesion (RECIST criteria), WHO PS 0–2, adequate baseline organs functions. Stratification factors: institution, best response to T: PR or CR vs no response, visceral site: yes vs no, number of previous chemotherapy lines in metastatic disease: 1 vs 2. Efficacy was evaluated by radiological assessment every 6 wks; responses are confirmed at least 4 wks later. Results: Between 7/00 and 7/02 137 Pts have been randomized in 33 centers (68 in OXA arm and 69 in VIN arm). Main pts characteristics, safety (G 3–4 AE by pts) and efficacy (RR, PFS, OS) results are shown in the table below. The study was prematurely discontinued due to accrual difficulty related to competitive drugs introduced (Capecitabine®) in the same clinical setting. Conclusion: OXA-5FU combination achieve similar results in term of RR, PFS and OS and favorable safety profile when compared to VIN-5FU combination which is one of the most active CT regimen in post taxane MBC. No significant financial relationships to disclose.
Association of cardiovascular diseases, metabolic syndrome and obstructive sleep apnea: Data from 1,000 Japanease PSG cases
Authors: Akemi Matsuo, Makoto Kosaka, Nobumitsu Kobayashi, Toshimichi Horiuchi, Toshihiko Agatsuma, Atsuhito Ushiki, Shintaro Kanda, Keishi Keishi
Journal: European Respiratory Journal (2012)

Background: Obstructive sleep apnea (OSA) is usually associated with cardiovascular diseases and also metabolic syndrome including diabetes, lipid metabolism

Objectives: The aim of the study was to evaluate the prevalence of hypertension (HT), diabetes mellitus (DM), hyperlipidemia (HL), and cardiovascular diseases (CVD) in the Japanease with proven OSA.

Methods: We retrospectively analyzed the data accrued in 1,000 patients who underwent the first time polysomnography (PSG) in our hospital from June 2001. They were 836 males and 164 females, the mean age of 54.5 years, the mean body mass index (BMI) of 26.0kg/m2, and the mean apnea-hypopnea index (AHI) of 38.0. We examined the association between OSA and cardiovascular diseases, metabolic syndrome.

Results: 938 between 1,000 patients were diagnosed with OSA. 41.2% of patients with OSA had HT compared with 21.0% of patients with non-OSA. And the OSA patients had 18.6% of DM, 45.3% of HL, 25.2% of liver dysfunction, 7.6% of CVD, comparing with 6.5% of DM, 29.0% of HL, 19.4% of liver dysfunction, and 3.3% of CVD in the non-OSA patients. In addition, the OSA patients treated with continuous positive airway pressure (CPAP) had 69.7% of HT, 23.8% of DM, 77.1% of HL, 40.7% of Liver dysfunction, and 21.2% of CVD. The blood pressure was reduced significantly by CPAP.

Conclusions: The risk of HT, DM, and CVD in OSA patients was almost two times more than those of non-OSA patients. We suggested that the OSA patients with higher severity OSA patients tended with a higher rate of complications.
PET FES measures in vivo pharmacodynamics of endocrine therapy
Authors: H. M. Linden, D. A. Mankoff, K. A. Krohn, J. M. Link, S. Stekhova, R. B. Livingston, J. R. Gralow, G. K. Ellis, B. Kurland, L. Peterson, E. K. Schubert
Journal: Journal of Clinical Oncology (2007)

14110 Background: Many clinical options are available for management of hormone sensitive breast cancer, including agents which lower estrogen levels such as aromatase inhibitors (AIs) and agents with block ligand binding to receptor such as tamoxifen (TAM) or fulvestrant (FUL). Estrogen receptor (ER) function is essential for sensitivity to hormonal manipulation in breast cancer treatment. We and others have previously shown that functional ER imaging using PET FES predicts response to hormonal therapy using a quantitative threshold of SUV &gt;1.5. Herein we report that FES PET provides a unique insight into in vivo pharmacodynamics of ER therapy. We hypothesized that the impact of therapy on estradiol binding to ER, measured by FES PET, differs between AIs and ER antagonists, and that early changes in receptor expression/occupancy show efficacy of drug at the tumor target. Methods: Patients undergoing treatment with AI, TAM, or FUL underwent baseline PET FDG and FES, and follow-up PET FES imaging at 2–8 weeks post initiation of therapy. Results: We observed the following changes in FES uptake on hormonal therapy: Mean percent change in FES SUV were 54% decline for TAM and FUL vs. 14% decline for AI treated patients (p&lt;.001). Patients on TAM showed complete blockade of tumor FES uptake on therapy (5/5 with residual SUV &lt;1.5), whereas patients on FUL had variable uptake and incomplete blockade at tumor sites in most patients (4/11 with residual SUV &lt;1.5) (p &lt; .05 FUL vs. TAM), despite consistent blockade of uterine FES uptake in patients where the uterus was visualized pre-FUL. Patients on AI therapy (n=14) had variable tumor uptake following treatment initiation. Conclusions: PET FES effectively monitors the in vivo activity of therapy. Estrogen blocking therapies result in a greater change in tumoral estradiol binding than in ligand depletion. TAM effectively blocks uptake of FES as would be predicted by the mechanism of action of this agent. However, FUL (while blocking uterine uptake) incompletely blocks tumor uptake, providing a mechanism to explain reduced activity of this agent in some patients. Ongoing analysis is designed to assess whether early changes in FES predict response or clinical benefit. No significant financial relationships to disclose.
Isolation of NDM-1-producing Klebsiella pnemoniae in Ireland, July 2011
Authors: H McDermott, D Morris, E McArdle, G O'Mahony, S Kelly, M Cormican, R Cunney
Journal: Eurosurveillance (2012)

We report the identification of New Delhi metallo-betalactamase 1 (NDM-1)-producing Klebsiella pnemoniae in Ireland. The organism was resistant to multiple antibiotic classes, including carbapenems, and PCR and sequencing confirmed the presence of the blaNDM-1 gene, carried on a 98 kb plasmid. The organism was isolated from an infant, who was born in India and moved to Ireland at the age of four months. This is the first reported isolation of an NDM-1-producing Enterobacteriaceae strain in Ireland.
The Prevention of Epilepsy
Authors: Mark Agostini
Journal: JAMA Neurology (2016)

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The effect of pegylated liposomal doxorubicin plus bortezomib in multiple myeloma patients with renal insufficiency
Authors: J. Blade, P. Sonneveld, J. San Miguel, H. Sutherland, R. Hajek, A. Nagler, A. Spencer, T. Robak, J. L. Harousseau, R. Z. Orlowski
Journal: Journal of Clinical Oncology (2008)

8562 Background: Renal dysfunction (RD) is common in patients with multiple myeloma (MM) and has been associated with poor outcomes. Orlowski et al, 2007, demonstrated that pegylated liposomal doxorubicin (PLD) + bortezomib (B) for pts with relapsed/refractory MM who have received at least one prior therapy significantly increased median time to progression (TTP) (9.3 vs. 6.5 months, p = 0.00004) compared with B alone. We wished to determine the efficacy and feasibility of PLD + B in relapsed/refractory MM patients with renal insufficiency (RI) (creatinine clearance (CrCl) < 60 ml/min). Methods: Eligible pts who were randomized received bolus IV B 1.3 mg/m2 on days 1, 4, 8 and 11 of each 3-week cycle (n = 322) or the same B regimen plus IV PLD 30 mg/m2 on day 4 (n = 324) of each cycle. 193 pts with RI from this trial were analyzed retrospectively to determine the impact of RI on the efficacy and safety of PLD + B, as well as the effect on renal function. Pts with severe RI (CrCl ≤ 30 ml/min) were excluded. Results: The mean number of PLD + B cycles administered was comparable between the two subgroups (5.1 in the RI subgroup vs. 5.0 in the non-RI subgroup). For the RI subgroup, median TTP was 10.9 (95% CI: 9.1, n/a) and 6.5 (95% CI: 5.3, 7.2) months in the PLD + B and B arms, respectively (p = 0.002). These results are consistent with the benefit of PLD + B demonstrated in the overall study population. There was a steady improvement in renal function over the course of treatment in both the PLD + B and B treatment arms. The incidence of grade 3/4 anemia, diarrhea and pneumonia were more common than in the RI subgroup compared to the non-RI group. Conclusion: RI does not compromise the efficacy or tolerability of PLD + B in relapsed/refractory MM pts. Treatment with PLD + B or B alone appears to improve renal function in relapsed/refractory MM pts with RI. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene, Centocor, Inc, Janssen-Cilag (Spain), Johnson & Johnson, Millennium, Ortho Biotech Celgene, Janssen-Cilag, Janssen-Cilag (Spain), Johnson & Johnson, Millennium, Ortho Biotech, Pharmion Janssen-Cilag, Janssen-Cilag (Spain), Johnson & Johnson, Ortho Biotech
Prognosis of lung cancer patients with high preoperative carcinoembryonic antigen (CEA) level: Are they surgical candidates
Authors: R. Kawachi, K. Suzuki, H. Kunitoh, S.-I. Watanabe, H. Asamura, R. Tsuchiya
Journal: Journal of Clinical Oncology (2004)

7181 Background: Elevated preoperative serum carcinoembryonic antigen (CEA) level has been reported to be a poor prognostic factor in non-small cell lung cancer (NSCLC). Surgical indication remains controversial in clinical (c-) stage I NSCLC patients with very high CEA levels. Methods: Between Jan. 1985 and Dec. 2000, 1502 patients with c-stage I NSCLC underwent surgical resection at the National Cancer Center Hospital, Tokyo, Japan. They were retrospectively analyzed for preoerative CEA level, pathologic (p-) stage and postoperative prognosis. Patients were divided into three groups according to CEA levels: Group A (n=1077, CEA< 5.0ng/ml), Group B (n=394, 5.0 ≤ CEA < 50ng/ml), and Group C (n=31, 50ng/ml ≤ CEA). Results: The p-stages of the 1502 patients were: stage I in 909 patients (60.5%), stage II in 464 (30.9%), stage III in 52 (3.5%) and stage IV in 64(4.3%). Group C patients were significantly (P < 0.0001) upstaged post-operatively; among the 31 patients in Group C, 4 (12.9%) had p-stage II disease, 12 (38.7%) stage III, and 4 (12.9%) stage IV. Among the 1077/394 patients in Group A/B, 259 (24.0%) /175 (44.4%) were upstage to p-stage II or more, respectively. The 5-year survival was 81.8% in Group A (n=1077), 63.5% in Group B (n=394) and 28.2% in Group C (P < 0.0001). There were 7 long-term survivors (> 5 years) in Group C. Conclusions: Patients with high CEA levels (50ng/ml ≤) significantly had advanced disease in terms of p-stage. High CEA level was a poor prognostic factor. However, we did observe long term survivors in this group, and high CEA per se is not a contraindication for surgical resection after intensive preoperative evaluation. No significant financial relationships to disclose.
GERD and anxiety in patients with severe COPD
Authors: Sherif Alsayed
Journal: European Respiratory Journal (2011)

Objectives:  To detect the impact of anxiety on shaping the prevalence of gastro-intestinal reflux disease (GERD) in patients with severs chronic obstructive pulmonary disease (COPD).   Methods:  We examined the prevalence of symptomatic GERD, using the Vigneri score, in 29 male patients with COPD. Esophageal 24 h pH monitoring was used to document the diagnosis of GERD in symptomatic group. Beck Anxiety inventory was used to detect the impact of anxiety on expressing GERD symptoms.   Results:  Reflux disease symptoms were recorded in eighteen patients of the studied group (62%). GERD was diagnosed, based on esophageal 24 h PH monitoring, in only 11 patients of those who expressing symptoms of GERD. Mean of Anxiety score was correlated significantly with the number and frequency of symptom presentation in patient with symptoms of GERD reflecting the attribution of differnt symptoms of anxiety to the GERD syndrom. Also Anxiety scores correlated positively with time (total) PH reflecting the effect of anxiety on the sverity of GERD syndrom.   Conclusion:  Patients with severe chronic obstructive pulmonary disease have a high prevalence of symptomatic gastro-oesophageal reflux. However True GERD was documented in a fewer number of them. Psychological factors, such as anxiety and somatisation may play a role, particularly in those patients without esophageal inflammation.
Safety and efficacy of tirapazamine (TPZ) combined with cyclophosphamide (C) and doxorubicin (D) in rhabdomyosarcoma (RMS) at first relapse/disease progression
Authors: P. P. Breitfeld, L. Mascarenhas, E. R. Lyden, C. N. Paidas, S. S. Donaldson, D. M. Parham, D. S. Hawkins, W. H. Meyer
Journal: Journal of Clinical Oncology (2008)

10035 Background: Patients with RMS in first relapse/disease progression have a poor prognosis. TPZ, a hypoxic cell toxin, has been shown to enhance activity of traditional cytotoxic chemotherapy. Methods: Eligible patients comprised those with biopsy proven RMS, < 21 years of age at original diagnosis, and unfavorable prognosis at first relapse/progression; those who had stable or progressive disease (n=53) on an upfront randomized Phase II window utilizing two schedules of irinotecan/vincristine (CPT-11/VCR); and those who refused (n=2) or were ineligible (n=29) for the randomized trial, TPZ 330 mg/m2 IV followed by C 1.2 g/m2 IV and D 75 mg/m2 IV were administered at weeks 1, 4, 10 19 and 28 alternating with ifosfamide and etoposide at weeks 7, 13, 16, 22, 25 and 31. The primary endpoint was safety. DLT was defined as Grade 4 infection, any hearing loss ≥ 40 db at 2000 MHz > 5days, and any ≥ Grade 3 vomiting, stomatitis, cardiotoxicity or other non-hematopoietic toxicity. Post-recurrence survival was the secondary endpoint. Results: 83 patients were exposed to TPZ combined with CD. Grade 3 or greater toxicities experienced, included vomiting (26.8%), stomatitis (12%), myalgia (8.5%), infection (5%), heart failure (6%) and ototoxicity (2.4%). There was one death due to congestive heart failure. All other toxicities were expected from the known toxicity profile of TPZ and were less than the a priori determined boundaries requiring TPZ dose de-escalation. The 1-year FFS (95% CI) and OS (95% CI) following TPZ-CD for those who had stable or progressive disease on CPT-11/VCR were 12% (3%, 28%) and 33% (18%, 48%), respectively. The 1-year FFS and OS for those that did not receive the CPT-11/VCR window were 36% (16%, 57%) and 74% (53%, 83%), respectively. Conclusions: The combination of TPZ- CD chemotherapy has an acceptable toxicity profile. This combination can now be investigated in target cancers in children. No significant financial relationships to disclose.
Abstract 514: Metabolomic Analysis of the Transition from Cardiac Hypertrophy to Failure
Authors: Takao Kato, Tetsuo Shioi, Shinichiro Niizuma, Yodo Tamaki, Yasutaka Inuzuka, Tsuneaki Kawashima, Yoshitaka Iwanaga, Toru Kita, Tomoyoshi Soga
Journal: Circulation (2007)
Factors influencing efficacy of BiPAP therapy in severe obstructive sleep apnea
Authors: Vratislav Sedlák, Ondrej Kudela, Michal Kopecký, Michal Svarc, Petr Smolík, Vít Havel
Journal: European Respiratory Journal (2013)

Introduction and background:  Severe obstructive apnea is current medical problem associated with obesity epidemic. There is frequently observed failure of bi-level positive pressure support therapy in patient with obesity and comorbidities as bronchial obstruction, cardiac failure. Aims and objectives:  Our hypothesis was that comorbidities, excessive daytime sleepiness (EDS, Epworth Sleep Scale), obesity and bronchial obstruction influences failure of BiPAP as a first choice therapy and requires volume assisted non-invasive ventilation (AVAPS). We compared these parameters in 32 consecutively examined patients reffered for obstructive sleep apnea syndrom to sleep lab and recieved BiPAP (n=17) or AVAPS (n=15) due to insufficent efffect of BiPAP.  Results:  BiPAP and AVAPS groups did not differ in gender, age, BMI, comorbidities (stroke, coronary, hearth, disease, obstructive lung disease) and smoking history (all p>0.05). In AVAPS group was higher t90% (percentage of time below 90% oxygen saturation) (66.6 vs 46.1, p=0.03), EDS (p=0.03), apnea/hyponea index were compareble (58.7 vs 48.9, p=0.17). In AVAPS group were lower FEV1% (51.4% vs 67.8%, p=0.01).  Conclusion:  Severe obstructive sleep apnea is frequently associated with comorbidities. Presence of higher bronchial obstruction plays a role in a potential failure of BiPAP as a first line therapy. Future studies are needed to assess efficacy of bronchodilatation therapy in improvement of efficacy and adherence to BiPAP.