tbuckley/cabot-search huggingface dataset:
Circulating tumor cells (CTC) and prostate specific antigen (PSA) as response indicator biomarkers in chemotherapy-naïve patients with progressive castration-resistant prostate cancer (CRPC) treated with MDV3100.
Authors: A. Anand, H. I. Scher, T. M. Beer, C. S. Higano, D. C. Danila, M. Taplin, E. Efstathiou, M. Hirmand, C. L. Sawyers, G. Heller
Journal: Journal of Clinical Oncology (2010)

4546 Background: The availability of reliable indicators of treatment efficacy is a critical unmet need in drug development for CRPC. MDV3100 is a second-generation oral androgen receptor antagonist that induces a prolonged apoptotic response in xenograft models and is active in men with progressive CRPC. We explored outcomes based on PSA and CTC number in relation to radiographic progression. Methods: 65 chemotherapy-naive patients with progressive CRPC were treated at doses of 30 to 360 mg/day. PSA levels were measured monthly, and CTC number at baseline, wks 4 and 12 using the CellSearch assay. A “PSA response” was defined as 3 consecutive declines within 12 wks of the start of treatment. Time to radiographic progression free survival (RPFS) was assessed by Prostate Cancer Working Group 2 criteria. The likelihood ratio test from the Cox proportional hazards model was used to determine the factors associated with RPFS, defined as being alive without progression. Results: The RPFS probability at 12 months was 0.56 (95% CI: 0.43, 0.73) with a median follow up of 13 months (2.4 to 26). 48 (74%) of the 65 pts were evaluable at the 12 wk landmark. CTC number, PSA, and PSA response, all assessed at 12 weeks, were all significant predictors of RPFS (p < 0.001). The joint model most predictive of RPFS time was CTC at 12 weeks and PSA response (3 consecutive declines). The concordance probability estimate (CPE) was used to measure the predictive accuracy of the model. The CPE for this joint model was 0.78, significantly higher than a model with each factor alone (CTC at 12 weeks – CPE= 0.63; PSA response- CPE=0.72). Conclusions: CTC at 12 weeks and PSA response provide independent predictive information for radiographic progression free survival time in chemotherapy-naive CRPC. Sustained PSA declines are consistent with the observed preclinical apoptotic response. Each biomarker may provide unique information. The results will be studied prospectively in an ongoing phase III randomized trial of MDV3100 with a survival endpoint. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Medivation Medivation Medivation Medivation Medivation, Veridex Medivation
Teens’ e-cigarette use rises as spending on advertising soars, says CDC
Authors: Michael McCarthy
Journal: BMJ (2016)

As spending on e-cigarette advertising has risen in the United States, there has been a nearly 10-fold increase in e-cigarette use by high school students, the Centers for Disease Control and Prevention said in a report released on 5 January.1

The report said that spending on e-cigarette advertising rose from $6.4m (£4.4m; €6m) in 2011 to an estimated $115m in 2014. Over the same period e-cigarette use among youth has risen. Reported use of e-cigarettes in the past 30 days among high school students increased from 1.5% in 2011 to 13.4% in 2014 and among middle school students from 1.6% to 3.9%, the report said.

The CDC’s director, Tom Frieden, said that advertisements used many of the same themes that were used to sell cigarettes, including “independence, rebellion, and sex.” …
Airway surface liquid homeostasis in cystic fibrosis: pathophysiology and therapeutic targets
Authors: Iram J Haq, Michael A Gray, James P Garnett, Christopher Ward, Malcolm Brodlie
Journal: Thorax (2015)

Cystic fibrosis (CF) is a life-limiting disease characterised by recurrent respiratory infections, inflammation and lung damage. The volume and composition of the airway surface liquid (ASL) are important in maintaining ciliary function, mucociliary clearance and antimicrobial properties of the airway. In CF, these homeostatic mechanisms are impaired, leading to a dehydrated and acidic ASL. ASL volume depletion in CF is secondary to defective anion transport by the abnormal cystic fibrosis transmembrane conductance regulator protein (CFTR). Abnormal CFTR mediated bicarbonate transport creates an unfavourable, acidic environment, which impairs antimicrobial function and alters mucus properties and clearance. These disease mechanisms create a disordered airway milieu, consisting of thick mucopurulent secretions and chronic bacterial infection. In addition to CFTR, there are additional ion channels and transporters in the apical airway epithelium that play a role in maintaining ASL homeostasis. These include the epithelial sodium channel (ENaC), the solute carrier 26A (SLC26A) family of anion exchangers, and calcium-activated chloride channels. In this review we discuss how the ASL is abnormal in CF and how targeting these alternative channels and transporters could provide an attractive therapeutic strategy to correct the underlying ASL abnormalities evident in CF.
Therapeutic and palliative benefit from single-agent irinotecan in multiply treated and highly refractory cases of lymphoma
Authors: D. D. Caces, J. Halaas, P. Hamlin, A. Noy, T. Kewalramani, C. S. Portlock, A. D. Zelenetz, O. A. O'Connor, J. F. Gerecitano
Journal: Journal of Clinical Oncology (2009)

e19554 Background: Multiple reports corroborate a role for irinotecan in the treatment of lymphoma. This study describes the Memorial Sloan Kettering experience with single-agent irinotecan in the management of heavily pretreated and highly refractory cases of lymphoma. Methods: Adult patients with histologically diagnosed relapsed or refractory lymphoma treated with irinotecan between 1/2001 and 8/2008 were identified. Treatment responses were evaluated based on the Revised Response Criteria for Malignant Lymphoma. Adverse reactions were evaluated based on the NCI Common Terminology Criteria for Adverse Events. Results: 30 patients were identified, 27 (90%) of whom received irinotecan after 3 or more prior regimens. 4 patients had Hodgkin Lymphoma (HL) and 26 had Non-Hodgkin lymphoma (NHL): 17 DLBCL, 6 transformed follicular lymphoma, 1 mantle cell lymphoma, 1 T-cell lymphoma and 1 Burkitt's. 25 patients were evaluable for response. 5 achieved an objective response (overall response rate 20%); 2 achieved complete remission (CR) and 3 partial remissions (PR). 8 patients (32%) had stable disease and 12 (48%) progressed on treatment. The median duration of response was 2.8 months (2.6–3.2), the median progression-free survival was 1.3 months (0.36 to 7.67) and the median overall survival was 3.9 months (0.30–63.4). Of the total cohort, 11 (36.6%) attained a clinically demonstrable improvement in symptomatology; 3 had resolution of pain syndromes, 5 had a reduction in the size or quantity of palpable masses, 2 had diminished fluid retention and 1 had an overall improvement in functional status. Adverse events occurring in more than 20% of cases included diarrhea (80%), leukopenia (67%), fatigue (36.6%) and thrombocytopenia (26.7%). Less common reactions included fever, febrile neutropenia, neuropathy, nausea and vomiting. Conclusions: Irinotecan has utility even in multiply treated and highly refractory cases of lymphoma. It can mitigate symptoms resulting from bulky disease and shows potential as a palliative treatment option. Although ORR was only 20%, two CRs were achieved suggesting benefit in select patients. Strategies that limit adverse reactions may enhance the agent's effectiveness in refractory lymphoma. No significant financial relationships to disclose.
Respiratory response to histamine- and methylcholine-induced bronchospasm in nonsmokers and asymptomatic smokers
Authors: J Savoy, M Louis, MH Kryger, A Forster
Journal: European Respiratory Journal (1988)

The respiratory response to bronchospasms of the same magnitude induced by inhalation of histamine or methylcholine was measured non-invasively, using bellow pneumographs, in nonsmokers and asymptomatic smokers. In each subject, tidal volume (VT), breathing frequency (f) and inspiratory time (TI) were obtained on two different days, in a randomized crossover fashion, with the following sequence: basal conditions, after inhalation of buffered saline as a control and after histamine or methylcholine inhalation. Basal and control conditions did not differ from each other and were the same for both groups. The respiratory responses to both bronchoconstrictors did not differ from each other and were also the same in both groups: VT increased, f and TI remained unchanged. Thus, VT/TI, an index of respiratory drive, also increased. In nonsmokers the increased VT/TI and the associated increase in minute ventilation were both correlated to the decrease in FEV1. These correlations were not found in smokers. Although they have different effects on airway irritant receptors, inhaled histamine and methylcholine induce the same respiratory response in nonsmokers and smokers. Thus, the presumed smoking-related changes in airway mucosa permeability do not seem to influence the direct stimulating effect of histamine on these endings. The absence of correlation between FEV1 and VT/TI changes in smokers suggest that smoking might affect the respiratory drive in acute drug-induced bronchospasm.
A inmunohistochemical expression profile as prognostic factor in locally advanced gastric cancer relapse
Authors: J. de Castro, M. Sereno, M. A. Garcia Cabezas, E. Casado, C. Belda-Iniesta, P. Cejas, J. Barriuso, J. A. Fresno, J. Feliu, M. Nistal, M. Gonzalez-Baron
Journal: Journal of Clinical Oncology (2005)

9697 Background: Surgical resection of gastric adenocarcinoma is curative in less than 40% of patients, so local regional or distance recurrence occurs in 40–60% of cases. New prognostic and predictive factors are needed to define the best candidates to receive adjuvant treatment. Methods: Expression of Bcl-2,p53,Cox-2,HER-2,Epo-R,β-catenin and E-cadherin proteins were evaluated by immunohistochemistry on 45 selected parafin-embedded gastrectomy specimens of gastric adenocarcinomas using an indirect inmunoperoxidase technique. All patients had received adjuvant treatment according to McDonald’s protocol(NEJM,2001;345:725). Inmunohistochemical staining for these proteins was correlated with clinico-pathological features: stage, histological subtype, differentiation, macroscopic appearance and recurrence. Results: Correlation with clinico-pathological features:p53 overexpression was higher in III-IVA vs IB-II (81%vs53%,p<0.049).In the intestinal type vs diffuse type we found p53 (91%vs51%,p<0.002) and Cox-2 (86%vs66%,p<0.001) overexpression, strong staining for Epo-R (95%vs72%,p <0.04)and lack of staining for expression of HER-2 (95%vs45%,p<0.0001). Normal inmunohistochemical expression of β-catenin occurred in 95%(p<0,02)of protruding gastric carcinoma(typeI in Borman classification)and in 91% intestinal subtype,as seen with E-cadherin.None expression changes were observed between differentiated vs undifferentiated gastric cancer. Recurrence expression profile:45 cases were studied and we found 15 recurrences(33.3%)at 2 years of follow-up.The inmunohistochemical profile was similar in 9 of the 15 cases(60%):Lack of staining for Bcl-2 and HER-2,normal expression of β-catenin and E-cadherin and overexpression of for p53,Cox-2 and Epo-R.Conversely, this inmunophenotype appeared only in 3 of 30(10%) cases that didn’t relapse after 2 years of follow-up,(p<0.01). Conclusions: These findings suggest that it could be possible to identify a pattern expression of p53, Bcl-2, Cox-2,HER-2,Epo-R,β-catenin and E-cadherin proteins to select gastric cancer resected patients with a worse prognosis who could benefit from an adjuvant treatment. No significant financial relationships to disclose.
Influence of surgery on metachronous distant metastases and survival in rectal cancer.
Authors: F Köckerling, M A Reymond, A Altendorf-Hofmann, O Dworak, W Hohenberger
Journal: Journal of Clinical Oncology (1998)

PURPOSE Total mesorectal excision (TME) and other technical surgical factors reduce local recurrence rate in rectal cancer. Scientific evidence of the positive effect of optimal surgery on survival is locking. Whether a reduction in the incidence of distant metastases can be achieved with optimal surgery is uncertain. We examine the effects of the quality of surgery, as reflected by local recurrence rate, on survival and the incidence of initial distant metastases. PATIENTS AND METHODS Between 1974 and 1991, 1,581 consecutive patients who underwent curative resection (RO) for rectal carcinoma were monitored for recurrence and survival. TME was introduced in 1985. No patient received adjuvant radiotherapy or chemotherapy. The median follow-up time was greater than 13 years. RESULTS The local recurrence rate decreased from 39.4% to 9.8% during the study period (P &lt; .0001). The observed 5-year survival rate improved from 50% to 71% (P &lt; .0001). Three hundred six patients with local recurrence had a significantly lower observed 5-year survival rate (P &lt; .0001). A total of 1,285 patients had no local recurrence, but 275 of them developed distant metastases (International Union Against Cancer [UICC] stage I, 8%; stage II, 16%; stage III, 40%). Better-quality surgery had no effect on the incidence of initial distant metastases, which remained constant (P = .44). CONCLUSION Quality of surgery is an independent prognostic factor for survival in rectal cancer, but has no influence on initial occurrence of distant metastases. Local recurrence cannot be considered an outcome criterion of adjuvant treatment without consideration of the surgeon as a risk factor.
Phase III study of docetaxel weekly (DW) versus every 3 weeks (D) in patients with metastatic breast cancer: Final results
Authors: E. Rivera, J. A. Mejia, B. Arun, R. Adinin, R. Walters, A. Brewster, K. Broglio, G. Yin, F. J. Esteva, G. N. Hortobagyi, V. Valero
Journal: Journal of Clinical Oncology (2006)

574 Background: D is a semi-synthetic taxane with significant activity in breast cancer. D is usually administered on an every 3-weeks schedule, however, studies have demonstrated drug efficacy and a different toxicity profile when administered on a weekly basis. In this study we compared the weekly schedule versus every 3-weeks to define the safest schedule with the highest efficacy. Methods: Patients (Pts) were enrolled if they had stage IV breast cancer and had received no more than one prior chemotherapy regimen for metastatic disease. Prior treatment with D was not allowed but adjuvant paclitaxel (P) was allowed if &gt; 12 months since the last dose. Pts were randomized to receive D at a starting dose of 75mg/m 2 on day 1 or DW at a dose of 35 mg/m 2 /week for 3 weeks followed by 1 week of rest every 28 days. Doses could be escalated to 100 mg/m 2 and 40mg/m 2 , respectively at the discretion of the investigator. Premedication with dexamethasone was given with each regimen. Results: From 1/2001 until 9/2004, a total of 125 pts were enrolled, 63 in the DW arm and 62 in the D arm. Thirty-nine and 10 pts had received prior anthracycline (A) and P respectively in the D arm while 32 and 11 pts had A and P in the DW arm. Median ages were 56 and 54 years in the D and DW arm, respectively. 118 pts were eligible for an efficacy analysis with a response rate of 35.6%; (95% CI, 23.6%, 49.1%) for the D arm vs 20.3%; (95% CI, 11.0%, 32.8%) for DW. There was no difference between D and DW in median PFS and OS, 5.7 vs 5.5 months (p = 0.46) and 18.3 vs 18.6 months (p = 0.34), respectively. There was a higher overall toxicity rate (grade 3 and 4) in the D arm vs DW, 88.1% vs 55.9% (p = 0.0001). There were 48 (81%) and 6 (10%) pts with grade ¾ granulocytopenia with 6 (10%) and 2 (3%) episodes of neutropenic fever in D vs DW, respectively. Grade 3/4 fatigue and myalgias were reported more often in D than DW, 15 (25%) and 8 (13.5%), and 16 (27%) and 2 (3%), respectively. Grade 3 epiphora was similar in both arms, 4 (7%) and 5 (8%) for D and DW, respectively. Conclusions: D has a higher response rate compare to DW but with a more pronounced toxicity profile. This needs to be kept in mind when making a treatment recommendation for patients with metastatic breast cancer. No difference in PFS or OS was observed between both arms. No significant financial relationships to disclose.
Effects of soy isoflavenes (genistein) on chemotherapy and radiotherapy toxicities in childhood cancer patients.
Authors: N. Tacyildiz, D. Ozyoruk, G. Yavuz, E. Unal, H. Dincaslan, F. Dogu, K. Sahin, O. Kucuk
Journal: Journal of Clinical Oncology (2010)

e20008 Background: Genistein, a soy isoflavone, has been shown to induce apoptosis and sensitize cancer cells to chemotherapy and radiotherapy in a variety of cancer cell types. However, there is no previous report regarding its protective effect on side effects of chemotherapy or radiotherapy in children with cancer. Methods: This study was designed to assess the effect of genistein on clinical or laboratory adverse effects of chemotherapy and radiotherapy in children with cancer. Cinical and laboratory findings were recorded for each child's no genistein first chemo cycle followed by chemotherapy cycles given with 8 mg/day genistein po. Six patients (ages 6-13 years) have been followed for 12-19 months. Diagnosis were: 2 neuroblastomas, one with metastatic Wilms' tumor, 1 patient with recurrent malignant mesenchimal tumor, 1 patient adrenocortical tumor and one patient with pons glioma. Cycles of chemo with OR no genistein have been analysed for mucositis, days with fever, duration of neutropenia, liver and kidney function tests, number of blood products suplementations. Results: Genistein is well tolerated in 57 chemo cycles in children with cancer. Serum genistein levels of patients during soy isoflavon supplementation (range: 0.215-0.411; median: 0.258 mg/L) were almost 2 times to 6 times higher than no supplementation genistein levels (range: 0.058–0.111; median 0.061 mg/L). Conclusions: These preliminary results suggest genistein may protect against chemotherapy and radiotherapy side effects in children with cancer. Comparison of the chemo cycles with or no genistein groups No genistein group(9 cycles) With genistein group (57 cycles) ANC Min-max(days) Median (days) Min-max(days) Median (days) ≤ 1500 0-14 8 0-17 4.5 ≤ 500 0-13 4 0-12 0 ≤ 100 0-6 3 0-8 0 Mucositis (grade I-IV) 0-4 3 0-3 0 Days with fever 0-5 2 0-4 0 Liver toxicity - 1 kolestasis Kidney toxicity - - Electrolite imbalance Hypopotasemia 3 4 Hyponatremia 2 Erithrocyte suppl. (unit) 0-4 1 0-5 0 Platelet suppl. (unit) 0-4 2 0-7 0 Antibiotic duration (days) 0-20 14 0-24* 0 GCSF supp. (days) 10-23 14 10-22 12 No significant financial relationships to disclose.
Dying with friends: implications for the psychotherapist
Authors: J M Lewis
Journal: American Journal of Psychiatry (1982)

The processes that augment the continued development of psychotherapeutic competence are little understood. One readily available source of learning is the life experiences of the therapist, particularly those situations which invoke intense affects and may increase empathic capacity. Some life experiences, however, lead to defenses against affect. In particular, situations in which the therapist feels helpless and those which confront the therapist with his or her own death may precipitate intense defenses. Several periods of such defensiveness resulting from discussions with four dying friends are explored and their implications for psychotherapeutic competence are analyzed.
Evaluation of neoadjuvant “window of opportunity” trials with targeted therapy in patients with surgically resectable non-small cell lung cancer.
Authors: B. M. Stiles, F. Mirza, Y. Chiu, J. L. Port, P. C. Lee, S. Paul, N. K. Altorki
Journal: Journal of Clinical Oncology (2010)

7060 Background: “Window of opportunity” trials administer a short course of targeted therapy (TT) prior to surgical resection. The purpose of this study was to assess the perioperative safety of this approach compared to standard therapy in early stage non-small cell lung cancer (NSCLC) patients. Methods: Patients (cstage I/II) enrolled in two clinical trials received either preoperative EGFR tyrosine kinase inhibitor (erlotinib, n=22) or VEGFR inhibitor (pazopanib, n=18), followed by surgical resection. These patients were propensity matched (1:2) using a logistic regression model to patients undergoing surgical resection alone. Preoperative time to resection, operative data, and postoperative complications were compared. Results: Patients were treated with neoadjuvant TT for a median of 21 days (range 11- 28). Time from first clinic visit to resection was significantly longer in this group than in control patients (48 vs. 25 days, p<0.0001). Despite the time delay, there was no significant increase in pathologic upstaging in the TT group compared to control (33% vs. 24%, p=0.38). There was no difference in operative time, blood loss, or thoracoscopic conversion rates between the TT and control groups (Table). There was no significant difference in the percentage of patients experiencing any complication (45% in TT group vs. 34% in control group, p=0.24) or in the overall rates of major complications (Table). There were no 30-day mortalities in either group. Conclusions: “Window of opportunity” trials are a powerful tool to assess response to TT in NSCLC patients, allowing for radiologic and pathologic assessment of treatment effects. Such trials can be safely undertaken prior to surgery in early stage NSCLC patients, with no increase in pathologic upstaging. Surgery can be performed safely in these patients with no increase in major complications. TT (N=40) Control (N=80) p value (Fisher's exact test) Operative factors Operative time (min.) 144 157 0.24 Estimated blood loss (cc) 205 195 0.79 Complications Any 45% 34% 0.24 Cardiovascular 20% 25% 0.65 Respiratory 23% 19% 0.64 Renal failure 0% 1% 1.0 Infectious 13% 8% 0.50 Operative 5% 1% 0.26 No significant financial relationships to disclose.
Caring for Older People: Launching the Nigerian edition of the BMJ: implications for Nigeria's health care
Authors: J. Ana
Journal: BMJ (1996)

The Nigerian Medical Forum sees the BMJ's Nigerian edition as a unique opportunity to fulfil one of its main objectives—the relief of sickness by advancing and sustaining medical education, training, and public health in Nigeria and other west African countries.

The forum was formed in 1991 to operate and serve as a medium for sending much-needed books, journals, equipment, and expertise to medical institutions all over Nigeria. The pioneer members realised that while the military political problems of Nigeria remained unsolved, vital social services such as healthcare delivery will regrettably be starved of financial and other resources. Every health statistic continues to deteriorate. The shelves in the medical libraries are empty or harbour outdated texts. Doctors, health professionals, and planners have little access to current literature and miss being part of the ongoing global revolution in science and technology which has made possible the advances in healthcare delivery that a decade ago were beyond the wildest dreams of society.

Historically, Nigerian doctors returned home by the first available transport after specialisation in Europe or America, but today there is no return home by these highly skilled and devoted professionals. The reason for this emigration varies, but perhaps the most widely cited is the lack of …