tbuckley/cabot-search huggingface dataset:
Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses
Authors: Mattias Brunström, Bo Carlberg
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To assess the effect of antihypertensive treatment on mortality and cardiovascular morbidity in people with diabetes mellitus, at different blood pressure levels. <b>Design</b>&nbsp;Systematic review and meta-analyses of randomised controlled trials. <b>Data sources</b>&nbsp;CENTRAL, Medline, Embase, and BIOSIS were searched using highly sensitive search strategies. When data required according to the protocol were missing but trials were potentially eligible, we contacted researchers, pharmaceutical companies, and authorities. <b>Eligibility criteria</b>&nbsp;Randomised controlled trials including 100 or more people with diabetes mellitus, treated for 12 months or more, comparing any antihypertensive agent against placebo, two agents against one, or different blood pressure targets. <b>Results</b>&nbsp;49 trials, including 73 738 participants, were included in the meta-analyses. Most of the participants had type 2 diabetes. If baseline systolic blood pressure was greater than 150 mm Hg, antihypertensive treatment reduced the risk of all cause mortality (relative risk 0.89, 95% confidence interval 0.80 to 0.99), cardiovascular mortality (0.75, 0.57 to 0.99), myocardial infarction (0.74, 0.63 to 0.87), stroke (0.77, 0.65 to 0.91), and end stage renal disease (0.82, 0.71 to 0.94). If baseline systolic blood pressure was 140-150 mm Hg, additional treatment reduced the risk of all cause mortality (0.87, 0.78 to 0.98), myocardial infarction (0.84, 0.76 to 0.93), and heart failure (0.80, 0.66 to 0.97). If baseline systolic blood pressure was less than 140 mm Hg, however, further treatment increased the risk of cardiovascular mortality (1.15, 1.00 to 1.32), with a tendency towards an increased risk of all cause mortality (1.05, 0.95 to 1.16). Metaregression analyses showed a worse treatment effect with lower baseline systolic blood pressures for cardiovascular mortality (1.15, 1.03 to 1.29 for each 10 mm Hg lower systolic blood pressure) and myocardial infarction (1.12, 1.03 to 1.22 for each 10 mm Hg lower systolic blood pressure). Patterns were similar for attained systolic blood pressure. <b>Conclusions</b>&nbsp;Antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic blood pressure more than 140 mm Hg. If systolic blood pressure is less than 140 mm Hg, however, further treatment is associated with an increased risk of cardiovascular death, with no observed benefit.
Differential Extraction of Tumor-Specific Transplantation Antigen and Embryonic Antigen From Simian Virus 40-and Adenovirus 7-Induced Sarcoma Cells of Hamsters With 1-Butanol and 3 &lt;italic&gt;M&lt;/italic&gt; Potassium Chloride&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J H Coggin, L D Gillis, W J Payne
Journal: JNCI Journal of the National Cancer Institute (1984)

Simian virus 40 (SV40)-induced sarcomas and adenovirus 7-induced sarcomas (Adv-7) exhibit both specific tumor-specific transplantation antigens (TSTA) and cross-protective embryonic antigens at the cell surface in the LAK:LVG(SYR) strain of Syrian golden hamsters. Specific SV40 TSTA could be released from the surfaces of living hamster sarcoma cells in a 2.5% crude 1-butanol extract (CBE) and served as immunogen to protect syngeneic recipients against subsequent homologous but not heterologous tumor cell challenge. The CBE-extracted SV40-induced TSTA (tumor-specific) was observed to be free of detectable, cross-protective embryonic antigens (EA) by tumor transplantation assays. The induction of cytotoxic lymphocyte-mediated immunity with the CBE-released TSTA was dependent on the administration of a single sensitizing injection of 12-20 micrograms antigen protein. Higher concentrations (50-1,000 micrograms) of the CBE tumor cell extract, given in a single injection, enhanced tumor growth as did two injections of 12.5 micrograms CBE-extracted SV40-induced TSTA at 1-week intervals. A cross-protective antigen(s), not detected in the CBE tumor extracts, was retained in the intact, 1-butanol-extracted SV40 and Adv-7-induced tumor cell lines after completion of the CBE extraction procedure and in similarly extracted 10-day hamster fetal cells. Some alterations in the normal immunogenicity of EA extracted with CBE followed by KCI from SV40-induced sarcoma cells could be detected in the transplantation assays and lymphocyte transformation assays, whereas EA extracted from CBE-KCI-treated Adv-7 cells or 10-day hamster fetal cells retained normal immunogenicity in vivo and in vitro. These procedures provide a means for successful separation of immunogenic SV40- and Adv-7-induced TSTA from detectable, biologically active, cross-protective EA from the surfaces of these sarcoma cells.
Low Level Laser Therapy for the Management of Cancer Therapy-Induced Oral Mucositis: a Retrospective Analysis in Patients with Cancer Other Than Head and Neck Cancer
Authors: L. Holvoet, S. Censabella, A. Maes, L. Noé, D. Luyten, E.J.R. Joosens, M. Brosens, P. Bulens, J. Mebis
Journal: Annals of Oncology (2014)
Impact of dose density of adjuvant chemotherapy for locally advanced urothelial cancer.
Authors: T. B. Dorff, J. Cai, G. Miranda, E. C. Skinner, A. Schuckman, S. G. Groshen, D. I. Quinn
Journal: Journal of Clinical Oncology (2010)

4567 Background: To investigate the importance of dose density for two chemotherapy regimens, gemcitabine and cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) during the adjuvant treatment of patients (pts) with locally advanced urothelial cancer after radical cystectomy. Methods: The USC Urology cystectomy database yielded 187 pts who received adjuvant chemotherapy from Apr. 1985 to Nov. 2007. Exact chemo doses and dates administered were available for 94 pts treated at USC (49 GC, 45 MVAC). Median age for the cohort is 65 years (range: 41-87), 83% male, 67% LN+. With median follow-up of 7.4 years (median 3.8 for GC, 12.7 for MVAC) there have been 23 deaths in the GC group and 28 in the MVAC group. In an exploratory analysis, we calculated the dose density for cisplatin, doxorubicin and gemcitabine as mg/m2/week. Using Cox regression the effect of chemo density on survival and recurrence was modeled as a continuous variable after adjusting for age, gender, and lymph node status. Results: For MVAC, full cisplatin density is 17.5 mg/m2/week and for GC given as a 21 day cycle it is 25.0 mg/m2/week. In our pts the median cisplatin density was 13.6 for MVAC and 23.3 for GC; the number of dose reductions and delays did not differ among the two groups. Cisplatin density correlated significantly with density of doxorubicin (r=0.84, p<0.001) and gemcitabine (r=0.90, p<0.001). Higher cisplatin density standardized by intended dose density had modest effect with improved recurrence-free survival (HR=0.95, p=0.058) and overall survival (HR=0.96, p=0.088). The effect was observed to be stronger in the GC group. The time from cystectomy to start of adjuvant chemo was significantly associated with recurrence and survival after controlling for age, gender, lymph node involvement, and treatment group. For pts with time to adjuvant chemo start >100 days the hazard ratio for death was 3.27 times higher (p=0.002) and for recurrence it was 3.23 times higher (p=0.002) than those starting adjuvant chemo within 100 days. Conclusions: These data yield a hypothesis that initiating treatment within 100 days of surgery, and maintaining or increasing the density of cisplatin during adjuvant chemotherapy, may be important for outcomes. No significant financial relationships to disclose.
Safety and efficacy trial of preoperative sequential chemo-radiation therapy for the nonsurgical treatment (NST) in early breast cancer (EBC): Japan Clinical Oncology Group trial (JCOG0306)
Authors: H. Mukai, T. Watanabe, M. Mitsumori, H. Tsuda, S. Nakamura, N. Masuda, N. Yamamoto, T. Shibata, A. Sato, K. Aogi
Journal: Journal of Clinical Oncology (2008)

601 Background: The combination of preoperative anthracycline-containing regimen and taxane can obtain a good pathologic complete response (pCR) rate for patients (pts) with EBC. To pursue higher pCR rate with maintaining good systemic control may lead to the NST in the future. The objective of this trial is to determine whether the addition of radiation therapy (RT) to chemotherapy (CT) can surpass the pCR rate of 50% as the first step of turning the NST into reality. Methods: We conducted a safety and efficacy trial of CT (4 courses of doxorubicin and cyclophosphamide [60/600mg/m2] followed by 12 courses of weekly paclitaxel [80mg/m2]) and RT (whole breast 45Gy + boost 10Gy) sequentially as a primary therapy in pts with stage I- IIIA (5.0cm > tumor size > 2.0cm) breast cancer (BC). All pts received mastectomy or lumpectomy 12–16 weeks after completion of RT to maximize the effect of RT. Primary endpoint was %pCR. pCR was assessed by the central pathological review board. Results: Between June 2004 and April 2005, 108 pts were enrolled in this trial. Median age was 50 years (range 23–69). 60%(65/108) were ER+, and 31%(34/108) had HER2 overexpression. The planned interim analysis after completion of accrual was carried out in Nov 2005. None of pCR was observed in first 7pts and study was terminated. In case of the pts had not undergone RT at the time, surgery without preoperative RT was recommended. A clinical response rate was 76%. 39(36%) had pCR+DCIS and 27(25%) had pCR. The rate of breast conserving surgery was 89%. 1 pt received debridement for radiation associated necrosis 3 months after lumpectomy and 3 pts needed antibiotics for postoperative wound infection. Other toxicities were mild to moderate. Conclusions: Preoperative sequential chemo-radiation therapy didn't increase the risk of operative complications and could achieve high rate of breast conserving surgery, even though expected % pCR was not achieved. Further therapeutic development is needed to realize NST for BC. No significant financial relationships to disclose.
Dual mechanistic function of MDSC subsets in melanoma resistance.
Authors: E. C. Borden, J. Ko Smith, P. A. Rayman, B. Jacobs, J. Ireland, D. Lindner, J. Finke
Journal: Journal of Clinical Oncology (2010)

8590 Background: Myeloid-derived suppressor cells (MDSC) accumulate in tumor-bearing hosts, suppress T-cell function and promote tumor-driven angiogenesis. Melanoma represents a resistant tumor type that is nevertheless highly immunogenic. Angiogenesis, closely linked to ulceration in primary tumors, plays a particularly important role in melanoma progression. The role of MDSC in promoting immune suppression and angiogenesis in melanoma is not fully understood. Methods: T-cell function (IFNγ production), MDSC subset frequencies (CD15+ neutrophilic, n-MDSC, CD14+ monocytic, m-MDSC, and CD15-CD14- immature, i-MDSC) and MDSC production of proangiogenic factors were measured in stage III/IV melanoma patients. n-MDSC and m-MDSC were induced from healthy donor blood by melanoma conditioned media (MCM). Induced n-MDSC and m-MDSC were compared in their ability to impact growth and vascularity in melanoma xenografts. Results: T- cells derived from melanoma patients were significantly deficient in Type-1 function compared to those from age-matched healthy donors (5.91±0.9%,n = 15 versus 18.01±1.4%, n = 21 IFNγ+CD3+ p < 0.0000002), and this was linked to elevations in all MDSC subsets (1.66±0.37% n-MDSC p = 0.001, 1.51±0.20% i-MDSC p = 0.2, 0.14±.025% m-MDSC p = 0.015; 3.3±0.46 total-MDSC p = 0.01, n = 15) compared to healthy donors (0.19±0.14% n-MDSC, 1.12±0.36% i-MDSC, 0.06±.019% m-MDSC; 1.37±0.46 total-MDSC, n = 5). Proteome array showed patient- derived MDSC produced several proangiogenic factors (IL-8, MMP8/9, platelet factor and VEGF). MCM bestowed healthy donor-derived neutrophils and monocytes with phenotypic and functional n- and m-MDSC identities. Studies examining enhancement of growth and blood vessel formation in xenografted melanoma tumors by induced n- and m-MDSC are ongoing. Conclusions: Tumor-driven n-MDSC and m-MDSC induction diminishes the potential effectiveness of antitumor immunity and promotes angiogenesis in melanoma. Further identification of those factors involved in this induction, as well as strategies aimed at reversing MDSC in melanoma using drugs such as sunitinib, could have potential therapeutic impact in melanoma. No significant financial relationships to disclose.
Association between comorbidities and lack of surgical therapy for elderly women with endometrial cancer
Authors: A. Ahmed, T. Buekers
Journal: Journal of Clinical Oncology (2008)

20681 Background: Comorbidity in cancer has been shown to be a major determinant in treatment selection and survival. Elderly women with endometrial carcinoma are less likely to undergo cancer-directed surgery. Associated comorbidities may be one factor to explain withholding cancer-directed surgery for elderly women with endometrial carcinoma. Methods: Women, ages 50 years and older, with endometrial carcinoma who were treated at the University of Iowa from 1990–2002 and did not receive cancer-directed surgery were identified and their medical records were reviewed. Comorbidity was measured with the Charlson Comorbidity Index (CCI) and the Adult Comorbidity Evaluation-27 (ACE-27). The CCI score is the most widely used comorbidity index in oncology; the CCI measures the presence or absence of 19 medical conditions with total scores ranging from 0–37. The ACE-27 is a newer 27 item comorbidity index which takes into account the severity of a given comorbid condition with grade score from 0–3, with 3 representing severe comorbidity. Physician rationale for not performing hysterectomy was recorded. Comparisons were made between the two age categories in regards to CCI, ACE-27 scores and recorded physician rationale. Results: Twenty-two patients were included in the analysis, with 10 in the 50–64 years category (group 1) and 12 in the 65 and older age category (group 2). The mean age in group 1 was 58.2 years with a range of 51–64 years. The mean age in group 2 was 77 years with a range of 71–89 years. Physician rationale for not performing hysterectomy differed between the two age groups; in group 1, 40% had comorbid conditions which precluded surgical intervention versus 75% of women in group 2. The ACE-27 and CCI scores were similar in the two groups. The average scores for the CCI for groups 1 and 2 were 2.0 and 3.3 respectively and the ACE-27 grade for groups 1 and 2 were 1.7 and 2.2 respectively. Conclusions: Elderly women with endometrial carcinoma who did not undergo cancer-directed surgery had more observed comorbid conditions as stated by treating physicians which precluded surgical intervention. However, validated comorbidity indices such as the Adult Comorbidity Evaluation-27 and the Charlson Comorbidity Index do not support this observation. No significant financial relationships to disclose.
Kent GPs commission surgical services from France
Authors: Helen Mooney
Journal: BMJ (2015)

NHS patients in Kent will have the option of travelling to France for surgery, after the Centre Hospitalier de Calais won a contract to provide treatment to NHS patients of the South Kent Coast clinical commissioning group (CCG).

The CCG recently invited organisations across Europe to tender to provide general surgery, gynaecology, cataract surgery, pain management, and orthopaedics.

Hazel Carpenter, accountable officer for the CCG, …
The Risk of Major Hemorrhage with CKD
Authors: Amber O. Molnar, Sarah E. Bota, Amit X. Garg, Ziv Harel, Ngan Lam, Eric McArthur, Gihad Nesrallah, Jeffrey Perl, Manish M. Sood
Journal: Journal of the American Society of Nephrology (2016)

New staging systems for CKD account for both reduced eGFR and albuminuria; whether each measure associates with greater risk of hemorrhage is unclear. In this retrospective cohort study (2002–2010), we grouped 516,197 adults ≥40 years old by eGFR (≥90, 60 to &lt;90, 45 to &lt;60, 30 to &lt;45, 15 to &lt;30, or &lt;15 ml/min per 1.73 m 2 ) and urine albumin-to-creatinine ratio (ACR; &gt;300, 30–300, or &lt;30 mg/g) to examine incidence of hemorrhage. The 3-year cumulative incidence of hemorrhage increased 20-fold across declining eGFR and increasing urine ACR groupings (highest eGFR/lowest ACR: 0.5%; lowest eGFR/highest ACR: 10.1%). Urine ACR altered the association of eGFR with hemorrhage ( P &lt;0.001). In adjusted models using the highest eGFR/lowest ACR grouping as the referent, patients with eGFR=15 to &lt;30 ml/min per 1.73 m 2 had adjusted relative risks of hemorrhage of 1.9 (95% confidence interval [95% CI], 1.5 to 2.4) with the lowest ACR and 3.7 (95% CI, 3.0 to 4.5) with the highest ACR. Patients with the highest eGFR/highest ACR had an adjusted relative risk of hemorrhage of 2.3 (95% CI, 1.8 to 2.9), comparable with the risk for patients with the lowest eGFR/lowest ACR. The associations attenuated but remained significant after adjustment for anticoagulant and antiplatelet use in patients ≥66 years old. The risk of hemorrhage differed by urine ACR in high risk subgroups. Our data show that declining eGFR and increasing albuminuria each independently increase hemorrhage risk. Strategies to reduce hemorrhage events among patients with CKD are warranted.
A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765, a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced solid tumors
Authors: P. LoRusso, B. Markman, J. Tabernero, R. Shazer, L. Nguyen, E. Heath, A. Patnaik, K. Papadopoulos
Journal: Journal of Clinical Oncology (2009)

3502 Background: XL765 is a potent and selective inhibitor of Class I PI3K isoforms, TORC1, and TORC2. XL765 has shown dose-dependent target modulation and tumor growth inhibition or shrinkage in multiple human xenografts. Methods: Pts receive XL765 bid or qd for 28-day cycles. PK and pharmacodynamic analyses are performed. Tumor response is assessed by RECIST every 8 weeks. Results: To date, 34 pts have been dosed with XL765; 26 pts on a bid regimen (15–120mg) and 8 pts on a qd regimen (70–100 mg). Maximum administered doses are 120 mg bid and 100 mg qd. Dose-limiting toxicities (DLTs) occurred at 120 mg bid and 60 mg bid and included elevated hepatic transaminases (2), anorexia/hypophosphatemia (1), rash (1), and nausea/vomiting (1). Grade &gt; 2 increase in transaminases, including one possibly related serious adverse event of Grade 4, occurred in 3 of 7 pts at 120 mg bid. Non-specific neurological complaints (1) and rash (1) were the DLTs that occurred at 100 mg qd. The most common (&gt; 10% of pts) related adverse events were elevated liver enzymes, nausea and diarrhea. XL765 exposure increased with increasing doses (15–120 mg bid). Median t max was 1–3 h post-dose. Mean t 1/2,z ranged from 3 to 9 h at steady-state. Repeat dosing (bid or qd) resulted in moderate to no drug accumulation. XL765 augmented food-induced increases in plasma insulin, but not glucose, in an exposure-dependent fashion. Robust pharmacodynamic modulation of PI3K pathway signaling in PBMCs, hair follicles, skin, and tumors was evident following administration of XL765. These effects were exposure-dependent for some biomarkers in PBMCs and hair. Five pts had durable stable disease (&gt; 3 months): appendiceal cancer (15 mg bid) 8 cycles; RCC (15 mg bid) 4 cycles; NSCLC (30 mg bid) 4 cycles; mesothelioma (60 mg bid) 10 cycles; CRC (100 mg qd) 6 cycles. Conclusions: In this phase I study, XL765 has exhibited potent pharmacodynamic activity at generally well tolerated doses. PI3K pathway inhibition of ∼60–90% in hair and skin was seen at multiple tolerable doses. [Table: see text]
Abstract 18977: Trends in Use of Thrombolytic Therapy Among Fee-For-Service Medicare Beneficiaries With Acute Pulmonary Embolism
Authors: Behnood Bikdeli, Yun Wang, Karl Minges, Brahmajee K Nallamothu, Nancy Kim, Mayur Desai, Frederick A Masoudi, John A Spertus, Samuel Z Goldhaber, Harlan M Krumholz
Journal: Circulation (2013)

Background: Thrombolytic therapy may improve the outcomes of select patients with acute pulmonary embolism (PE); however, it has historically rarely been used in older adults. Contemporary national trends in use of thrombolytic therapy among elderly patients with PE are not known. Methods: Using the inpatient Medicare Standard Analytic Files, we identified all Fee-For-Service patients aged ≥65 years old with a principal discharge diagnosis of PE between 1999 and 2010 and also identified those who received thrombolytic therapy. We used the Vital Status Files to determine rates of 30-day and 1-year mortality and fitted mixed-effects models to calculate adjusted mortality. Results: During the study period, there were 545,131 patients with a principal discharge diagnosis of PE, of whom 7158 (1.3%) received thrombolysis. The number of PE patients undergoing thrombolysis increased from 380 in 1999 to 840 in 2010 (P&lt;0.001 for linear trend), in large part owing to increased utilization among patients 65-74 years. The proportion of patients with PE receiving thrombolysis changed from 12 per 1000 in 1999 to 16 per 1000 in 2010 (p=0.09 for linear trend). In-hospital mortality rates among patients receiving thrombolysis ranged between 15% and 21.2% in the study period. Adjusted 30-day and 1-year mortality rates ranged between 17.9% to 23% and 26.1% to 31.4% across the years. Conclusions: Recent trials (e.g., PEITHO) suggest thrombolysis may confer benefits in PE, even among older adults. We observed more widespread use in older age groups in recent years, but thrombolysis is still rarely applied for elderly patients compared with other age groups.