tbuckley/cabot-search huggingface dataset:
Failure of Ovarian Suppression With Gonadotropin-Releasing Hormone Analogs to Preserve Fertility
Authors: Kutluk Oktay, Volkan Turan
Journal: JAMA Oncology (2015)

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A novel technique to determine dead space ventilation in ARDS
Authors: Joeke Nollet, Jonne Doorduin, Manon Vugts, Lisanne Roesthuis, Johannes van der Hoeven, Leo Heunks
Journal: European Respiratory Journal (2014)

Introduction:  Bohr9s dead space is the portion of tidal volume (V T ) not participating in gas exchange with pulmonary blood flow. This parameter is important in patients with acute respiratory distress syndrome (ARDS) for treatment follow-up, ventilator settings optimization and prognostication. However, dead space calculation is cumbersome using current techniques. Recently, a novel technique based on volumetric capnography (VC) was validated. Our aim was to compare VC with current techniques in ARDS patients and controls.   Methods:  In 15 ARDS patients and 15 controls (post-operative cardiac surgery) dead space (V D ) was calculated with VC using the Bohr equation: V D /V T  = (PACO 2 -PeCO 2 )/PACO 2 , where PACO 2  and PeCO 2  are alveolar and mixed expired CO 2  tension. Both variables were calculated from a mathematical fit of the volumetric capnogram. Dead space was also calculated using the Bohr-Enghoff modification (arterial CO 2  tension (PaCO 2 ) instead of PACO 2 ). PeCO 2  was measured in expired air using a Douglas bag (DB) and via indirect calorimetry with a metabolic monitor (MM).   Results:  In ARDS patients, dead space determined with VC (53±8%) was lower compared to DB (68±8%,  p  p  2  determined with MM (3.2±0.4 kPa) was higher compared to DB (2.5±0.3 kPa,  p  p  2  was higher with DB (2.1±0.4 kPa) compared to VC (1.8±0.4 kPa,  p  2  was higher than PACO 2  in the controls (5.2±0.5 vs. 4.3±0.5 kPa,  p  p    Conclusion:  Current techniques, using PaCO 2  instead of PACO 2,  overestimate dead space through pulmonary shunting. Volumetric capnography measures true Bohr9s dead space.
Abstract 2489: Left Ventricular Diastolic Functional Reserve during Exercise in Patients with Impaired Myocardial Relaxation at Rest
Authors: Jong-Won Ha, Eui-Young Choi, Chi-Young Shim, Se-Jung Yoon, Jin-Mi Kim, Jeong-Ah Ahn, Se-Wha Lee, Se-Joong Rim, Namsik Chung
Journal: Circulation (2007)
Utility of bronchoalveolar lavage in vasculitis patients
Authors: Joanne Heaton, Noshaba Naz, Sarah Hardy, Janice Harper
Journal: European Respiratory Journal (2014)

Introduction: Value of bronchoalveolar lavage(BAL) in evaluating patients with vasculitis is without any doubt. BAL is performed in patients with diffuse parenchymal opacities on CT to assess for alveolar haemorrhage and to obtain samples for cytological and microbiological analysis. There are currently no guidelines regarding how to approach immunosuppressed vasculitis patients presenting with respiratory symptoms.  AIM: To assess the percentage of positive BAL performed in immunosuppressed vasculitis patients who presented with respiratory symptoms.  Method: Retrospective analysis of patients diagnosed with vasculitis who underwent BAL between 2011 and 2013. Twenty patients were identified. Hospital electronic record system and clinic letters were used for data collection. Patients were assessed in terms of primary diagnosis, presenting complaints, CT chest indications and findings, BAL findings and further management.  Results: Overall, 50% of BALs were positive. 18 CT scans were abnormal and 2 CT scans were normal with negative BAL. The abnormal findings on BAL included CMV, PCP, HSV, influenza, rhinovirus and corona virus, with several patients having multiple pathogens. Patients with negative BAL were treated for a flare of their vasculitis, community acquired pneumonia or pulmonary oedema, based on clinical judgement.  Conclusion: Early BAL is crucial in diagnosis and management of vasculitis patients presenting with respiratory symptoms and CT abnormalities. Negative CT scan could possibly predict negative BAL. With the results from BAL, confident treatment plans can be made and prolonged hospital admissions can be avoided. There is a need to establish local/international consensus guidelines.
Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy.
Authors: P Fumoleau, F M Delgado, T Delozier, A Monnier, M A Gil Delgado, P Kerbrat, E Garcia-Giralt, R Keiling, M Namer, M T Closon
Journal: Journal of Clinical Oncology (1993)

PURPOSE This study investigated the therapeutic effects of single-agent intravenous (IV) weekly Navelbine (vinorelbine or 5'-nor-anhydro-vinblastine; Pierre Fabre Médicament, Boulogne, France), a semisynthetic vinca alkaloid, in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer. PATIENTS AND METHODS One hundred fifty-seven patients with assessable advanced or metastatic breast cancer who had received no prior chemotherapy were entered onto the study. They were stratified into five groups according to the main assessable tumor target: lung, liver, lymph nodes, skin, and others. One hundred forty-five patients were assessable for toxicity and response using World Health Organization (WHO) criteria; the 12 patients who were not evaluated were excluded because they were found not to meet the eligibility criteria. Navelbine was administered as a weekly 30-mg/m2 short IV infusion, and treatment was continued until disease progression. RESULTS The overall response rate (WHO criteria) was 41% (complete response [CR], 7%; partial response [PR], 34%; 95% confidence interval [CI], 33% to 49%). In addition, 30% of the patients had stable disease. The response rate according to target was lymph nodes (28 of 42), 67%; liver (nine of 39), 23%; lung (10 of 30), 33%; skin (21 of 30), 70%; primary tumor (10 of 16), 56%; and bone (three of 10), 30%. The median time to treatment failure was 6 months and the median survival was 18 months. A total of 1,673 cycles were given to 145 eligible patients. At least one episode of WHO grade 3 or 4 granulocytopenia was seen in 72% of the patients. Nausea and/or vomiting, anemia, and/or thrombocytopenia were seen in less than 1% of cycles. Other side effects were rare, and additional toxicities were documented in the following proportions of patients: grade 2 to 3 alopecia, 8%; infectious episodes, 6%; and peripheral neuropathy, 3%. CONCLUSION Our data confirm that Navelbine has major single-agent antitumor activity as front-line therapy in advanced breast cancer. Given its excellent tolerance profile and low toxicity, it should be considered for inclusion in first-line combination chemotherapy regimens.
KI67: Analysis of its expression and prognostic significance in a resected non small cell lung cancer population
Authors: Rocio Magdalena Diaz Campos, Ricardo Garcia Lujan, Eduardo de Miguel Poch, Rodrigo Alonso Moralejo, Fernando Lopez-Rios Moreno
Journal: European Respiratory Journal (2012)

Ki67 is a nuclear protein involved in the cellular proliferation regulation; its expression is associated with cancer and usually has a prognostic significance.

AIM.- To study Ki67 expression and its prognostic significance in a resected non small cell lung cancer (NSCLC) population, in general and by types.

POPULATION AND METHODS.- We included all the patients, with a completely resected NSCLC stage IAp to stage IIBp, seen at our hospital from 1998 to 2003. The Ki67 expression was studied by inmunohistochemistry techniques. We used the Chi square test to analyze the differences in the Ki67 expression between the squamous cell carcinoma and adenocarcinoma and a bivariate analysis to study the prognostic significance of Ki67 expression according to the 5 years survival using the Wilcoxon-Gehan (W-G) test and the log rank (L-R).

RESULTS.- We included 146 patients, 91% were men with a median age of 67 yo. 99 were squamous cell carcinoma, 37 adenocarcinoma and 10 large cell carcinoma. The Ki67 expression was positive in 56% cases, negative in 42% and no valid in 2%. The Ki67 positive expression found in the different types of NSCLC is shown in Table 1 and the prognostic significance of Ki67 expression, in NSCLC and its different types, is shown in Table 2.

![Figure][1] 



CONCLUSION.- In the population studied, the Ki67 expression was higher in the squamous cell carcinoma and was associated with a bad prognosis.

 [1]: pending:yes
Chronic fatigue in prostate cancer patients after radical prostatectomy (RP) or high-dose radiotherapy (RAD)
Authors: A. E. Kyrdalen, E. Hernes, S. D. Fossa, A. A. Dahl
Journal: Journal of Clinical Oncology (2009)

5164 Background: Chronic fatigue (CF) is frequent in cancer patients, but has been less studied in prostate cancer patients (PCPs). This study compares CF in PCPs treated with RP or RAD(≥70Gy), who have never received any hormonal therapy. Methods: In 2006 we addressed all Norwegian PCPs who had been diagnosed in 2004 and were alive (N = 2,997). Among the 2,194 PCPs (73%) responding we identified 332 patients with RP and 183 with RAD 12–32 months before our survey. The PCPs returned a mailed questionnaire covering fatigue, quality of life, urinary and bowel bother, sexual function, comorbidity, and lifestyle. Hormonal therapy identified by the national prescription database or self-report, lead to exclusion. Caseness of CF was based on the Fatigue Questionnaire. Results: Caseness of CF was observed in 13.6% of men with RP (95%CI 9.9–17.2%) and in 25.7% after RAD (95%CI 19.4–32.0%) (p = 0.001). The prevalence in the RP group was similar to the norm observed in Norwegian men &gt;60 years. PCPs with RP or RAD had similar prevalence of bother regarding urinary symptoms (13 vs 16%, p = 0.13), while more RAD than RP patients reported bother due to bowel symptoms (24 vs 4%, p &lt; 0.001). Sexual functioning showed a better score in the RAD versus the RP group (p &lt; 0001). In multivariate regression analysis treatment modality did not show any significant association with CF (p = 0.25). In contrast, physical and mental quality of life (both p &lt; 0.001) and bother due to bowel problems (p = 0.005) were associated with CF caseness. No significant associations were found between urinary bother, sexual function and CF caseness. Conclusions: This national study of PCP treated with curative intention showed a much higher prevalence of CF after RAD compared to RP. In multivariate analysis treatment modality was not significantly associated with CF caseness. Bowel bother was more common after RAD, and showed a significant association with CF caseness, however, with a wide confidence interval. No significant financial relationships to disclose.
Abstract 5836: The Effect of Survivor Bias on Surgical Outcomes in Infective Endocarditis
Authors: Raymond Sy, Leonard Kritharides
Journal: Circulation (2008)

Introduction Recent studies have demonstrated conflicting results regarding the benefits of surgery in infective endocarditis (IE). In particular, studies have not accounted for potential survivor bias associated with surgery since patients who survive longer have more opportunities to undergo surgery. Hypothesis We explored the effect of survivor bias on surgical outcomes in IE. Methods We studied 223 consecutive patients admitted with left-sided IE to two centers between 1996–2006. All-cause mortality at one year was compared between medically-treated patients and those undergoing surgery using a Cox proportional-hazards model with adjustment for a patient’s propensity to surgery. To adjust for survivor bias, analyses were repeated with surgery as a time-dependent covariate. Results Compared to medically-treated patients (n= 161), patients undergoing surgery (n= 62) had significantly lower mortality at one year (21.0% vs 38.5%, p= 0.017) with an unadjusted hazard ratio of 0.47 (95%CI 0.26–0.86, p= 0.014). However, patients undergoing surgery were significantly younger (46.9± 15.1 yrs vs 57.9± 19.2 yrs, p&lt; 0.001) and had lower Charlson comorbidity scores (0.7± 1.5 vs 1.4± 1.9, p= 0.007), but were more likely to have severe heart failure (NYHA FC III-IV, 27% vs. 12%, p&lt; 0.001). Baseline differences between groups were taken into account by developing a regression model for surgery and assigning a propensity score for surgery to each patient based on this model. Significant predictors of surgery were NYHA class (p&lt; 0.001), aortic valve involvement (p&lt; 0.001), severe regurgitation (p= 0.016), and lower hemoglobin at baseline (p= 0.012). After adjustment for the propensity score, there remained a significant benefit for surgery (hazard ratio 0.24, 95%CI 0.11–0.52, p&lt; 0.001). However, the benefits of surgery were diminished and no longer significant when it was evaluated as a time-dependent covariate (hazard ratio 0.87, 95%CI 0.43–1.78, p= 0.87), suggesting that the apparent benefits of surgery may be related to survivor bias. Conclusions Survivor bias may have a significant effect on the evaluation of outcomes associated with surgery in IE and such bias can be reduced with the use of time-dependent covariate analysis.
The usefulness of high resolution computed tomography in burned patients with inhalation injury
Authors: Cheol-Hong Kim, In-Gyu Hyun
Journal: European Respiratory Journal (2012)

Background: Smoke inhalation may affect both airway and lung parenchyma. Then, airway injury can be easily assessed by bronchoscopy, but lung parenchymal injury might be evaluated by other imaging modalities. The aim of this study is to assess lung parenchymal injury by high resolution computed tomography (HRCT) in burned patients who had been identified inhalation injury bronchoscopically.  Methods: The bronchoscopy with biopsy at carina or 2 nd  carina and HRCT were performed in burned patients with inhalation injury initially after admission. Positive HRCT findings include peribronchial ground glass appearance with/or without consolidation, bronchial wall thickening, branching linear attenuation, atelectasis, interlobular septal thickening and bronchiectasis. We analyzed APACHE II scores, PF ratio, the need for mechanical ventilation care, pneumonia and degrees of airway injury according to HRCT findings.  Results: 22 burned patients were enrolled. Bronchoscopy was performed in all and HRCT in 19. Of those, 10 patents (52.6%) showed positive HRCT findings. Between positive and negative HRCT, age, burn size and initial COHb were not significant different (43±17.3 vs. 37±13.8, p > 0.05; 14.9±21.76% vs. 0.56±0.73%, p > 0.05; 6.2±7.68% vs. 11.5±8.64%, p > 0.05). Positive HRCT findings were closely associated with more frequencies of mechanical ventilation care and pneumonia, and higher APACHE II scores and PF ratio, and more severe airway injury.  Conclusions: HRCT in burned patients with inhalation injury may be useful to assess lung parenchymal injury and to guide further therapy because radiographic evidence for lung parenchymal injury may predict the severity of inhalation injury.
Population pharmacokinetics (PK) and association of PK and clinical outcomes of rituximab in patients with non-Hodgkin's lymphoma.
Authors: A. Yin, J. Li, D. Hurst, J. Visich
Journal: Journal of Clinical Oncology (2010)

e13108 Background: Rituximab is effective and widely used in NHL. To increase our understanding of its PK characteristics and relation to clinical outcomes, we analyzed data from the rituximab pivotal trial (IDEC102-05) in patients with relapsed low-grade or follicular B-cell NHL who were treated with 4 weekly rituximab doses. Methods: Population PK (POP-PK) of rituximab was performed based on 1,848 serum samples from 161 patients using nonlinear mixed-effects modeling (NONMEM VI) software. The association of rituximab PK with response and time to progression (TTP) in the follicular lymphoma (FL) subgroup was evaluated by logistic and Cox regression, respectively. Results: Rituximab clearance was best described by a two-compartment model with time varying clearance comprised of two terms—a target-independent pathway as with other endogenous IgG antibodies, which is unchanged throughout treatment, and a target-mediated pathway that decreases from its initial value following infusion at a constant decay rate related to the extent of B cell/tumor-burden at baseline. In the FL subgroup (N=111), a positive association of rituximab serum concentrations pre-second infusion with overall response rate and TTP was observed among patients with low concentrations (< 35 ug/ml): odds ratio =1.72 (95% CI: 1.14-2.60, p=0.009) for response and HR=0.75 (95% CI: 0.64-0.91, p=0.0032) for TTP (per 5 ug/ml). In contrast, no association with TTP or OR was seen for the FL patients with higher serum concentrations (≥ 35 ug/ml). Similar results were observed for timpoints at 1 and 3 mo post-treatment, and the association is not qualitatively affected by baseline characteristics or disease factors. Conclusions: POP-PK studies suggest that the lower rituximab serum levels are associated with the larger tumor burden and/or antigen load. Among FL patients, higher rituximab concentrations are associated with better clinical outcomes only on those with serum concentrations in a low range. Further studies would be necessary to identify the threshold of rituximab level sufficient to override the effects of tumor burden for FL patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Roche
Low biologic aggressiveness in breast cancer in women using hormone replacement therapy.
Authors: K Holli, J Isola, J Cuzick
Journal: Journal of Clinical Oncology (1998)

Hormone replacement therapy (HRT) has been associated with an increased risk for breast cancer. Cancers in women who use HRT are often less advanced, and lower mortality has been reported in those who use HRT than in nonusers. We sought to explain this by a comparison of indicators of tumor aggressiveness in patients who received HRT with those in patients who did not.A population-based cohort of 477 postmenopausal women with breast cancer were interviewed for the use, type, and duration of HRT. Clinical variables and indicators of tumor aggressiveness (histologic grade, hormone receptors, DNA ploidy, S-phase fraction, and c-erbB-2 oncoprotein overexpression) were analyzed.Breast tumors from HRT users were smaller (odds ratio, 0.47; P=.005), had better histologic differentiation (P=.04), and had a lower proliferation rate (S-phase fraction, P=.009) than tumors from nonusers. These differences persisted after adjustments for age and method of diagnosis (mammography screening v self-referral) by multiple logistic regression. No significant differences were observed in the estrogen (ER) or progesterone receptor content, c-erbB-2 oncogene overexpression, or axillary node involvement. A subgroup analysis showed that the tumor proliferation rates among HRT users were significantly lower only if HRT had been used at the time of diagnosis (P=.001). The type of HRT (estrogen v combination of estrogen and progesterone) was not associated with any clinical parameter or tumor phenotype. The association of HRT with lower proliferation rate and smaller tumor size was exclusively caused by ER-positive tumors (P=.0001 and P=.0035 v P > .1, respectively).The results indicate that breast cancer in women who receive HRT is biologically less aggressive than those without previous HRT. The lower cell-proliferation rate and smaller tumor size found in ER-positive tumors from current HRT users suggest a direct ER-mediated growth inhibitory effect of HRT on established breast tumors. This may at least partly explain why breast cancer in HRT users has a more favorable clinical course.
Monitor tells NHS providers to “look again” at year’s financial plans
Authors: Ingrid Torjesen
Journal: BMJ (2015)

Monitor, the regulator of health services in England, has ordered NHS service provider organisations to take emergency action to help stave off the “unprecedented” financial crisis facing the NHS.

A letter from David Bennett, Monitor’s chief executive, sent on 3 August, orders “all providers—even those planning for a surplus this year—to look again at their plans to see what more can be done.” The NHS was facing “an almost unprecedented financial challenge,” he …
Abstract 262: Slight Therapeutic Hypothermia (35°C to 36°C) for Post--Cardiac Arrest Syndrome Due to Ventricular Fibrillation with Low Left Cardiac Function Is a Feasible and Safe Possibility
Authors: Tomohiko Orita, Kenichirou Sasao, Yukitoshi Toyoda, Koichi Mukai, Mitsuhide Kitano, Yoshiaki Ito, Hiroshi Ishimori, Keisuke Hirano, Masatsugu Nakano, Masahiro Yamawaki, Motoharu Araki, Tamon Kato, Hideyuki Takimura, Yasunari Sakamoto, Ikki Komatsu, Takurou Takama, Kanai Nunoya, Reiko Tsukahara, Toshiya Muramatsu
Journal: Circulation (2011)

Background: Mild therapeutic hypothermia (32-34°C, 24-48 hours: mild TH) for post cardiac arrest syndrome (PCAS) due to ventricular fibrillation (VF) had been recommended in the American Heart Association (AHA) Guidelines 2005 (class IIa) and the International Liaison Committee on Resuscitation (ILCOR). In the AHA guidelines 2010, it has been recommended more strongly (class I). But it is still unknown what temperature is best for low cardiac function patients including acute myocardial infarction (AMI) cases. Sometimes executing mild TH for patients with severe left ventricular dysfunction are not so easy and safe because of hypotension, arrhythmias, unstable vital signs and so on. So we studied whether slight therapeutic hypothermia (35-36°C: Slight TH) was effective and safe compare with mild TH for PCAS due to VF. Methods: Consecutive PCAS patients who were witnessed, done by-stander cardiopulmonary resuscitation (CPR), confirmed VF caused by cardiac or coronary events and introduced therapeutic hypothermia for the latest 45 months were sorted into the GroupM (Mild TH, 34°C, 24-72 hours) and the GroupS (Slight TH, 35-36°C, 24-72 hours).The primary end point was a favorable neurologic outcome (cerebral performance category: CPC 1 or 2) in 28th days after cardiac arrest. Secondary end points were the changes of cardiac index (CI) after introducing therapeutic hypothermia, the time required to reach target temperature and the rate of complications (infections, bleeding, arrhythmias etc.) within fourteen days. Results: Thirty-five patients (twenty AMI cases) were studied (GroupM 20 patients and GroupS 15 patients). The rate of favorable neurologic outcome was available and did not differ significantly between the two groups (50% vs. 53%, p=0.85). The time to reach target temperature was significantly shorter in the GroupS (5.9h vs. 0.9h, p&lt;0.01). The decrease of CI was remarkable in the groupM (before TH/during TH, GroupM 2.8/2.2, GroupS 1.9/2.1, the changes of them were Δ32% vs. +0.05%, p&lt;0.01). The rate of complications did not differ significantly between them and there were no major complications. Conclusion: Slight therapeutic hypothermia for PCAS due to VF with low cardiac function is possibility feasible and safe.