tbuckley/cabot-search huggingface dataset:
Low parathyroid hormone status induced by high dialysate calcium is an independent risk factor for cardiovascular death in hemodialysis patients
Authors: Emilie Merle, Hubert Roth, Gérard M. London, Guillaume Jean, Thierry Hannedouche, Jean-Louis Bouchet, Tilman Drüeke, Denis Fouque, Eric Daugas
Journal: Kidney International (2016)

Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24 months. Patients were classified according to their Kidney Disease: Improving Global Outcomes PTH status at baseline and at 12 months, and mortality evaluated at 12 to 24 months using adjusted Cox analysis. Factors potentially involved in PTH status variability between baseline and 12 months were analyzed. A decrease in serum PTH from normal or high to low values between baseline and 12 months was associated with significantly increased cardiovascular mortality at 12 to 24 months (hazard ratio, 2.03; 95% confidence interval, 1.22-3.36). For patients with high or normal baseline PTH levels, the main independent factor at 6 months for a decrease to low PTH levels at 12 months was high dialysate calcium (1.75 mmol/L), whereas prescription of non-calcium-based phosphate binders was associated with a lower risk of PTH decrease. In the high cardiovascular (CV) mortality risk subgroup of patients who acquired a low PTH status at 12 months, the main independent factor at 12 months associated with significant 12- to 24-month CV mortality was high dialysate calcium (odds ratio, 5.44; 95% CI, 2.52-11.75). Thus, patients with a serum PTH decrease to low values after 1 year of hemodialysis treatment are at high risk of short-term CV death. High dialysate calcium was an important contributor to PTH oversuppression, and continued use was associated with increased CV mortality.
Neoadjuvant chemotherapy with paclitaxel, 5-fluorouracil and cisplatin is effective in the management of locally advanced carcinoma of pyriform fossa
Authors: I. B. Ambulkar, S. Goyle, S. H. Advani
Journal: Journal of Clinical Oncology (2008)

17039 Background: Neoadjuvant chemotherapy has been used effectively in the treatment of locally advanced head and neck cancers. We conducted a study to evaluate the efficacy and adverse events associated with neoadjuvant chemotherapy schedule comprised of paclitaxel, 5-fluorouracil and cisplatin from January 2005 to December 2007. Methods: Thirty patients with locally advanced pyriform fossa cancer were enrolled to receive paclitaxel 135 mg/m2 on day 1, 5-fluorouracil 500 mg/m2 on day 1, 2, 3 and cisplatin 25 mg/m2 on day 1, 2, 3 every 3 weekly for 3 cycles followed by response evaluation. All patients after completion of neoadjuvant chemotherapy were evaluated by CT scan and direct laryngoscopy. Results: From January 2005 to December 2007, 30 patients were enrolled: 24 were male and 7 female; median age was 58.4 yrs (38–80 yrs). Five patients (16.66%) achieved a complete response, 23 pts (76.66%) had partial response. Stable and progressive disease was observed in 1 pt (3.33%) each. The overall response rate was 93.32%. A total of 90 cycles of chemotherapy was delivered with a median of 3 cycles per patient. Grade 3 neutropenia, anemia, and thrombocytopenia were observed in 10%, 6.66% and 3.33% of cycles, respectively. With regard to nonhematologic toxicity, grade 3–4 nausea and vomiting, stomatitis and diarrhea were observed in 10%, 6.66% and 6.66% of patients, respectively. Conclusions: In our experience, neoadjuvant chemotherapy with paclitaxel, 5-fluorouracil and cisplatin-RT may be a good choice in treating locally advanced supraglottic laryngeal cancer. The toxicity profile was also manageable. No significant financial relationships to disclose.
Abstract 12042: The "Obesity Paradox" in Ambulatory Patients With Heart Failure With Preserved Ejection Fraction
Authors: Sukhdeep S Basra, Umair Khalid, Salim S Virani, Vijay Nambi, David Aguilar, Hani Jneid, Biykem Bozkurt, Anita Deswal
Journal: Circulation (2013)

Background:  The “obesity paradox”, wherein obesity is a risk factor for development of heart failure (HF) but is associated with better survival in HF, is well described in HF with reduced ejection fraction (HFrEF) and partly attributed to cardiac cachexia. However, cachexia is not usually associated with HF with preserved ejection fraction (HFpEF) and little is known about the existence of the paradox in HFpEF. Accordingly, we examined the prognostic significance of body mass index (BMI) on outcomes in HFpEF.   Methods:  We evaluated 2501 ambulatory patients with HFpEF from 153 VA healthcare facilities with 2-year follow-up. Kaplan Meier survival curves and Cox-proportional hazard models were used to examine the association of BMI with outcomes of mortality, HF hospitalization and all cause hospitalization.   Results:  In patients with HFpEF (age 71 ± 10 years, 91% males, 89% white), patients with higher BMI were significantly younger, had higher prevalence of hypertension, diabetes, and prior HF hospitalization, but lower prevalence of atrial fibrillation, anemia ((p≤0.001 for all) and chronic kidney disease (p=0.04). Compared to normal weight patients, patients with higher BMI had a lower risk of mortality (Log rank p≤0.001), but higher risk of HF hospitalization (p=0.038) (Figure), and similar risk of all cause hospitalization (p=0.77), which remained significant even after adjusting for baseline differences (Table).   Conclusions:  Our study suggests the presence of the “obesity paradox” even in patients with HFpEF, with higher BMI being independently associated with improved survival. However, higher BMI was also associated with a higher risk of HF hospitalizations.
Multicenter phase II study of liposomal doxorubicin (M) and docetaxel (T) as neoadjuvant treatment in patients with stage II - III breast cancer
Authors: A. Modolell, J. I. Mayordomo MD, J. M. Garcia-Bueno, I. Machengs, I. Alvarez, M. Centelles, H. Palombo, M. Burillo, A. Yubero, L. Murillo, R. Andrés
Journal: Journal of Clinical Oncology (2006)

10662 Background: T and M is a very active chemotherapy regimen for breast cancer. M has been shown to be as effective as doxorubicin at same doses while reducing the cardiotoxicity and causing less myelosuppression. This study was designed to evaluate clinical and pathological response rate (RR) and toxicity after induction chemotherapy in patient with breast cancer. Methods: Patients with histological confirmation of breast cancer (stage II-III and inflammatory), age &gt; 18 years, left ventricular eject fraction &gt; 45% and adequate bone marrow, renal and hepatic function were included in the study. Prior systemic therapy or radiotherapy and surgery for breast cancer were not allowed. Treatment: T (75 mg/m 2 ) iv and M (75 mg/m 2 ) iv, every 21 days during 4 cycles, followed by surgery. Results: To date 59 patients have been enrolled; 50 were included in this interim analysis, with a median age of 52 years old (28–76), ECOG PS 0, 88.0%; ECOG PS 1, 12.0%; breast location: right, 52.0%; peri-postmenopausal status, 44.9%. Positive hormonal receptor status was 63.3%. Histology was ductal carcinoma in 84.0%. Patients received a total of 188 cycles (median 4, range 2–4). Median relative dose intensity was 99% for T and for M. Efficacy: Nine patients were non-evaluable (7 on treatment, 1 consent withdrawal and 1 lost of follow-up). Of 41 evaluable patients, 5 achieved complete response (CR) (12.2%), 26 partial response (PR)(63.4%), 9 stable disease (SD) (22.0%) and 1 progressive disease (PD) (2.4%), resulting in a clinical response rate (RR) of 75.6% (95% CI: 62.5–88.7%). Surgery was performed in 40 patients: six (15.0%) of them had pathological (p) CR, 25 (62.5%) pPR, 9 (22.5%) pSD resulting in a pathological RR of 77.5% (95% CI: 64.6–90.4%). Median of time to progression and overall survival has not been achieved yet. Hematological toxicities grades III/IV per patient were neutropenia (14%), thrombocytopenia (4%), leukopenia (2%), anemia (2%) and febrile neutropenia (12%). Non-hematological grade III/IV toxicities per patient were asthenia (6%), nausea / vomiting (4%) and infection (4%). Conclusions: T and M every 21 days during 4 cycles as induction chemotherapy in stage II and III breast cancer is an active and well tolerated treatment. No significant financial relationships to disclose.
Phase I trial of docetaxel, carboplatin and lenalidomide in patients with advanced solid tumors
Authors: S. R. Kalmadi, M. Davis, A. Dowlati, S. O’Keefe, M. Cline-Burkhardt, R. J. Pelley, E. C. Borden, R. Dreicer, R. M. Bukowski, T. Mekhail
Journal: Journal of Clinical Oncology (2006)

13027 Lenalidomide (LEN) is an immunomodulatory derivative of thalidomide with significantly greater in vitro activity and different toxicity. It may interfere with the expression of angiogenic factors (TNF-alpha &amp; IL-6), vascular endothelial growth factor (VEGF) and induce apoptosis in resistant cell lines. In preclinical trials it has shown synergy with chemotherapy. Primary objective of this study was to determine the maximum tolerated doses (MTD) of docetaxel (D) and carboplatin (Cb), combined with oral LEN. Secondary objectives were toxicity and activity. Eligibility included pathologically proven solid tumors, ≤ 2 prior chemotherapy regimens, performance status ECOG 0/1, and adequate organ function. Patients (Pts) with active brain metastases, or prior treatment with D, Cb, or LEN, were excluded. Treatment was continued for a maximum of 6 cycles, followed by optional continuation of LEN until disease progression or toxicity. MTD was defined as the dose level (dl) immediately lower than that producing dose limiting toxicity (DLT) during cycle 1 in ≥ 2 of 3–6 pts. DLT were ≥ grade (G) 3 non-hematological, or G 4 hematological toxicity. No growth factors were used during cycle 1. Four pts were treated at dl I, D 60 mg/m2, and Cb AUC 6 on Day 1, and LEN 10 mg orally daily for 14 of a 21d cycle. Dose de-escalation was done following the first cohort due to DLT. 10 pts were treated at lower dl -1, D 60 mg/m2, and Cb AUC 6 on Day 1, and LEN 5 mg orally daily for 14 of a 21d cycle. 3 of 14 pts had prior chemotherapy. Tumors included non small cell lung cancer (NSCLC) (9), and one each with thymic, rectal, apocrine carcinoma, angiosarcoma and unknown primary. The median number of cycles was 4 (range 1–6). DLTs occurred in 3 of 4 pts at dl I (G 3 electrolyte (E) (2), G 4 neutropenia (N) (1) and 1 of 10 pts at dl-1 (G 4 N). Overall G 3/4 toxicities were: N (7), thrombocytopenia (2), and E (2). There were no treatment-related deaths or irreversible toxicities. Of the evaluable pts, 5 had a partial response (5/9 NSCLC), &amp; 5 had stable disease. D 60 mg/m2, and Cb AUC 6 on Day 1, and LEN 5 mg orally daily for 14 days of a 21 d cycle is the MTD without use of prophylactic growth factors. This combination is active and further evaluation in a phase II trial is warranted. [Table: see text]
Expression patterns of IL-1 receptor 1 in COPD lungs
Authors: Anders Bergqvist, Cecilia Andersson, Michiko Mori, Chris Van Hove, Leif Bjermer, Jonas Erjefält
Journal: European Respiratory Journal (2011)

Rationale:  Recent research in murine models suggests an important role of Interleukin-1 receptor 1 (IL-1R1) signalling in the pathogenesis of COPD. Yet, the features of IL-1R1 expression in human COPD patients remain poorly investigated. This study characterizes the expression of IL-1R1 in lung tissues from COPD patients and control subjects.   Methods:  Lung resections were obtained from 27 COPD patients; GOLD I (n=6), GOLD II-III (n=13) and GOLD IV (n=8). Never smoking controls (n=7) and smoking controls (n=6) served as controls. IL-1R1 expression was studied by immunohistochemistry and computerized image analysis. A double staining immunofluorescence protocol visualized IL-1R1 expressing cell populations.   Results:  The expression of IL-1R1 in small airway epithelium was significantly higher in GOLD IV vs. GOLD II-III patients (p=0.03). In the small airway lamina propria, there was no overall statistical difference between the groups (p=0.12), but there was a tendency towards a higher IL-1R1 expression in GOLD IV vs. GOLD II-III patients (uncorrected p=0.02). In the endothelium, IL-1R1 expression was similar between the groups (overall p=0.8). IL-1R1 was found to be expressed on multiple leukocyte populations such as T-cells, dendritic cells, macrophages and NK-cells.   Conclusions:  Our data suggest that at baseline conditions IL-1R1 is expressed in the airway epithelium, endothelial cells, and on multiple subepithelial leukocyte populations. Severe stages of COPD appear to be associated with increased IL-1R1 expression in small airway epithelium and in infiltrating cells in the lamina propria, a phenomenon that may participate in the abnormal immune reactions in advanced COPD.
Abstract 18378: Comparsion of Cerebral Protection Strategies on Immediate And Longterm Outcome of Patients With Stanford Type a Aortic Dissection
Authors: Marie-Elisabeth Stelzmueller, Dominik Wiedemann, Philipp Ogrodny, Michael Urban, Paul Obrovsky, Stephane Mahr, Alfred Kocher, Guenther Laufer, Marek Ehrlich
Journal: Circulation (2015)

Introduction: The optimal protection strategy for use during acute type A aortic dissection surgery is controversial. Hypothesis: To assess the efficacy and immediate and long-term results of different cerebral protection techniques in the treatment of acute type A aortic dissection. Methods: Between April 1987 and January 2015, 400 patients (270 male patients; mean age 58 years; range 15-88) with acute type A dissection underwent surgical aortic repair with an open distal anastomosis. Either hypothermic circulatory arrest alone at 18 °C (n = 111; 28%) or combined with retrograde cerebral perfusion (n = 117; 29%) or antegrade cerebral perfusion at 25 °C (n = 172; 43%) was used for cerebral protection. Results: The median circulatory arrest time was 35 minutes. The overall 30-day mortality was 16% (63 of 400). The 30-day mortality stratified by group was 20% (22 patients) in the hypothermic circulatory arrest group, 17% in the retrograde cerebral perfusion group (20 patients), and 12% (21 patients) in the antegrade cerebral perfusion group (P = .021). Permanent neurologic dysfunction occurred in 53 patients (14%), with statistically significant differences among the 3 groups (25% for hypothermic circulatory arrest, 13% for retrograde cerebral perfusion, and 7% for antegrade cerebral perfusion; P = 0.01). Univariate analysis showed a significant effect of the cerebral protection strategies on 30-day mortality and neurologic outcome. Kaplan-Meier analysis showed differences among the 3 groups with a 1-, 2-, and 5-year survival rate of 85%, 82%, and 77% with antegrade cerebral perfusion, 75%, 72%, and 66% with retrograde cerebral perfusion, and 65%, 64%, and 62% with hypothermic circulatory arrest alone (p=0.19). Conclusion: Antegrade cerebral perfusion group had a superior 30 day as well as midterm survival and inferior rate of PND. During the study period, several significant improvements in surgical as well anaesthesiological in treatment and management of acute type A aortic dissection were achieved. However, postoperative outcome of patients with type A dissection is multifactorial and independent predictors of mortality and permanent neurologic dysfunction were difficult to identify
Tobacco smoking: Still an important lifestyle component for adolescents and adults
Authors: Simona Apetrei
Journal: European Respiratory Journal (2012)

Tobacco use remains still,unfortunately,an important component of lifestyle for all ages Romanian people.The aim of this study was to highlight features of tobacco from different generations,adolescents and adults.Study groups:A-student smokers aged 14-18 years,B-smoking adults aged over 19.All subjects completed anonymous questionnaires about tobacco use.The prevalence of smoking was 21.8% for group A,35.6% for group B.The prevalence of smoking was relatively similar for males and females for group A-23.6% /20.3%,while for group B was more prevalent for males increased(52.4% /19.6%).Smoking prevalence was also similar for rural/urban areas for group A;for group B slightly increased in rural areas-62.3%.We obtained a low nicotine dependence in 70.2%of adolescents and high dependence in only 6.0% of them; in adults the medium dependence prevailed 49.1%,and high dependence occurred in 34.9% of cases.The mean age at wich they start smoking was13.8 years for group A and 15.2 for group B.In both groups we found a significant percentage of cases having at least one other smoker in their family-33.3% for adolescents and 20.8% for adults.In this study we found that the new generation is better informed about health risks of smoking(79.8%),but ignore that information,knowingly exposing themselves to risks.Although groups of study subjects were included only smokers in the two categories, it is worth mentioning that the percentage of ex-smokers was a significant(12.5%,respectively 23.8%).It should therefore promote a healthy lifestyle,without tobacco consumption,both adolescents and adults,in order to increase quality of life by preventing multiple pathology caused by tobacco.
Skin color parameters and Fitzpatrick phototypes in estimating the risk of skin cancer: A case-control study in the Polish population
Authors: Aneta Sitek, Iwona Rosset, Elżbieta Żądzińska, Anna Kasielska-Trojan, Aneta Neskoromna-Jędrzejczak, Bogusław Antoszewski
Journal: Journal of the American Academy of Dermatology (2016)
Gastrointestinal stromal tumor (GIST): Our experience
Authors: L. Tozzi, M. Di Bisceglie, A. De Bonis, M. Bisceglia, S. Ronga, M. P. Romano, P. Di Sebastiano, E. Maiello
Journal: Journal of Clinical Oncology (2008)

21513 Background: GISTs are mesenchymal neoplasms of the GI tract and represent 0.1–3% of GI neoplasms. Surgical resection is the first-line intervention for operable GISTs and remains the only effective treatment. However, more than half of all GIST patients present locally advanced, recurrent, or metastatic disease. Methods: From October 2001 at present, 42 pts (CD117-positivity) were detected in our hospital. Clinical presentation, treatment and outcomes were also examined in these pts. The main characteristics of these pts were as follows: median age: 58 yrs (range 29–83); sex (F/M): 22/20; primary tumor localization: stomach 25 (59.5%), small intestine 10 (24%), colon- rectum 2 (5%), retroperitoneum 4 (9.5%), liver 1 (2%); first symptoms: epigastric pain 16 (38%); abdominal pain 8 (19%); hematemesis 2 (5%); melena 4 (9.5%); grave anemia 7 (16%); palpable abdominal mass 2 (5%); defecation disorders 2 (5%); rectal bleeding 1 (2%); ascites 1 (2%). Radical surgical resection was performed in 35 pts (83%), 3 pts received a debulking surgery, and 4 pts showed advanced or metastatic disease. No postoperative mortality or major complications were observed. Results: Four pts with advanced/metastatic disease, received imatinib at the standard dose and we observed 1 PR (lasting 33 months), and 3 PD. With a median follow-up of 28 months, all but one of these pts are died. Eight pts (23%), classified in the high-risk class, developed recurrence: the median time to relapse was 8 months (range 2–11). In these pts, treated in first line with imatinib at standard dose, we achieved 2 PR, 4 SD (range 17+−43+ months), and 2 PD. In one pt with only liver relapsed disease, who obtained PR after an initial response induced by imatinib therapy, radical surgery was performed obtaining a CR lasting 35 months. Conclusions: Complete surgical resection remains in our experience also the standard treatment for GISTs. Histologic and immunohistochemical examinations appear essential for a definitive diagnosis and to assess the risk of aggressive behavior. However, in pts with advanced or relapsed disease treatment with imatinib achieve a high disease control rate. No significant financial relationships to disclose.
Abstract 247: Heparanase-overexpressed Mesenchymal Stem Cells Enhances Angiogenesis Via Hypoxia-inducible Factor-2α/Vascular Endothelial Growth Factor Receptor-2 Pathway
Authors: Xin Yang Hu, Ling Zhang, Jing Jin, Huiqiang Cheng, Han Chen, Jian-an Wang
Journal: Circulation Research (2014)

Background:  Heparanase is an endoglycosidase involved in the cleavage of the heparin sulfate and plays important role in tumor metastasis and angiogenesis. Here we showed heparanase - overexpressed mesenchymal stem cells (MSCs) promoted angiogenesis in rat model after femoral artery ligation, and its underlying mechanism was via endothelial cells migration by Hypoxia-Inducible Factor-2α (HIF-2α) / vascular endothelial growth factor receptor-2 (Flk-1) pathway and collateral formation.   Methods:  MSCs were transduced with heparanase (MSC  heparanase ), control cells were either nontransduced (MSC WT ) or transduced with empty vector (MSC Null ). The effect of human umbilical vein endothelial cells (HUVECs) migration, tube formation and the role for heparanase were determined by transwell, matrigel and arterial rings asaay after co-culture with MSC heparanase , MSC Null  and MSC WT  conditioned medium. Moreover, right femoral artery was occluded in rats receiving PBS or MSC Null  or MSC heparanase , blood flow recovery was assessed by laser-Doppler imaging (LDI) before surgery, immediately after operation, as well as 3, 7 and 14 days after occlusion, capillary density was measured at 14 days after occlusion.   Results:  In vivo , the group receiving MSC heparanase  had a fast recovery of blood flow at 7 days after occlusion and more capillary densities at 14 days after occlusion.  In vitro,  HUVECs treated with MSC heparanase  conditioned medium exhibited increased formation of capillary-like structures and promoted migration, compared with HUVECs treated with MSC Null  conditioned medium. All effects of MSC heparanase  conditioned medium were abolished by knockdown of HIF-2α and flk-1 with a selective shRNA and were absent in HUVECs. Mechanism studies revealed that heparanase increased the cellular accumulation of HIF-2α protein and affects its nuclear translocation, which regulates flk-1 and its downstream proteins: p38 and HSP27 expression.   Conclusions:  These findings identify heparanse as a key regulator in MSCs induced angiogenesis and collateral formation. Heparanse up-regulates HIF-2α and mediates Flk-1/p38/HSP27 pathway, which is necessary for angiogenesis and collateral artery network.
Extensive tumoral melanosis associated with ipilimumab-treated melanoma
Authors: K. Staser, D. Chen, J. Solus, I.S. Rosman, A. Schaffer, L. Cornelius, G.P. Linette, R.C. Fields
Journal: British Journal of Dermatology (2016)

Tumoral melanosis describes a pigmented lesion clinically similar to melanoma but on histology reveals dense aggregates of melanin-laden, benign macrophages without malignant cells. In the few reported cases so far, tumoral melanosis has arisen in the skin or lymph node of a patient with a regressed melanoma or an epithelioid tumour. As a marker of regressed primary melanoma, its discovery may prompt investigation and surveillance for undiagnosed local or metastatic disease. Here, we present a unique case of extensive tumoral melanosis arising during ipilimumab treatment of in-transit metastases from a previously excised melanoma.