tbuckley/cabot-search huggingface dataset:
The Memorial Sloan-Kettering Cancer Center (MSKCC) experience with outpatient administration of high-dose methotrexate with leucovorin rescue
Authors: S. M. Zelcer, M. Kellick, L. H. Wexler, R. Gorlick, P. A. Meyers
Journal: Journal of Clinical Oncology (2005)

9003 Background: We describe the safety and feasibility and incidence of leucovorin (LCV) dose modification for an outpatient high dose methotrexate (HDMTX) regimen. Methods: HD-MTX (12 g/m2) is administered in a pediatric day hospital (PDH) intravenously (IV) over 4 hours. Urinary alkalinization is achieved using an IV bolus of sodium bicarbonate followed by scheduled oral bicarbonate tablets, with supplemental dosing for any urine pH less than 7. Daily visits to the PDH follow and include IV hydration and MTX level monitoring. Overnight hydration is administered via an ambulatory infusion pump. LCV is begun 24 hours after MTX at a standard dose of 10 mg po q6h. The LCV dose is escalated between a range of 20 mg po q6h to 1 gm as a continuous IV drip over 24 hours according to an institutional algorithm for levels above 10,1, and 0.1 μmol/L at 24, 48, and 72 hours post MTX. Patients at risk of methotrexate toxicity including MTX levels >50 μmol/L at 24 hours, nephrotoxicity, dehydration, severe mucositis, infection and poor compliance are admitted to hospital. To evaluate our approach, we conducted a retrospective review of all patients (n=89) who received HDMTX at MSKCC between 1996–2002. Results: A total of 761 courses of MTX were administered, of which 83% were successfully completed as an outpatient. 52% of patients received standard dose leucovorin with 48% requiring a dose escalation. 28% were escalated to 20 mg q6h, 10% 30 mg q6h, 5% 50 mg q6h, and 5% required 1 g over 24 hours. 22 patients had MTX levels > 50 μmol/L during one or more courses, and all but one were retreated successfully as outpatients. Hepatotoxicity (reversible transaminitis) was present in the majority of patients. Grade III-IV nephrotoxicity and hematologic toxicity was observed in ≤ 0.5 and 13% of MTX courses respectively. Conclusions: Outpatient administration of HDMTX and the required supportive therapy is safe, effective and feasible using the described approach. Approximately half of the patients will require LCV dose modification based on serial monitoring. Patients who experience toxic levels of MTX can be safely re-treated in an outpatient setting. No significant financial relationships to disclose.
Effect of use of immunosuppressive drugs in peripheral and respiratory muscle strength in patients undergoing kidney transplantation
Authors: Luciana Chiavegato, Ana Paula Pereira, Juliana Sagin Pinto, Lais Azevedo, Adriana Lunardi
Journal: European Respiratory Journal (2013)

Transplantation is the best treatment option in the long term compared with maintenance dialysis in patients with chronic kidney disease. This treatment requires the mandatory use of immunosuppressive drugs for positive effects, however, the side effects of these medications on peripheral and respiratory muscle strength remain unknown. Objective: To evaluate, over the course of a month, the impact of immunosuppression in peripheral and respiratory muscle strength in renal transplant recipients. Methods: 22 patients were evaluated from a University Hospital preoperatively, on the 7th postoperative day and one month after renal transplantation, for respiratory muscle strength (MIP and MEP), handgrip strength and dose of immunosuppressant. Results: The 22 patients had a mean age of 36.29±9.87 years, BMI 23.25±4.05kg/m2, MIP=61.38 ± 20.54, MEP=61.05 ± 36.60, handgrip strength= 29.71 ± 11.35 kgf and dosage of 11.7±7.95 mg of immunosuppressive medications (Tacrolimus). Although a decrease in respiratory muscle strenght and handgrip was shown over time, it was not statistically significant. Conclusion: Our results show that even during the first month post renal transplantation, immunosuppression had no negative impact on peripheral and respiratory muscle strength.
Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009
Authors: Zobair M. Younossi, Munkhzul Otgonsuren, Linda Henry, Chapy Venkatesan, Alita Mishra, Madeline Erario, Sharon Hunt
Journal: Hepatology (2015)

Hepatocellular carcinoma (HCC) is increasingly reported in patients with nonalcoholic fatty liver disease (NAFLD). Our aim was to assess the prevalence and mortality of patients with NAFLD-HCC. We examined Surveillance, Epidemiology and End Results (SEER) registries (2004-2009) with Medicare-linkage files for HCC, which was identified by the International Classification of Diseases for Oncology, third edition codes using topography and morphology codes 8170-8175. Medicare-linked data was used to identify NAFLD, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease (ALD), and other liver disease using International Classification of Diseases, Ninth Revision, Clinical Modification codes. NAFLD was also defined by clinical diagnosis (cryptogenic cirrhosis, obese-diabetics with cryptogenic liver disease). A logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HCC. In addition, adjusted hazard ratios for 1-year mortality were estimated by Cox's proportional hazard regression. A total of 4,929 HCC cases and 14,937 controls without HCC were included. Of the HCC cases, 54.9% were related to HCV, 16.4% to ALD, 14.1% to NAFLD, and 9.5% to HBV. Across the 6-year period (2004 to 2009), the number of NAFLD-HCC showed a 9% annual increase. NAFLD-HCC were older, had shorter survival time, more heart disease, and were more likely to die from their primary liver cancer (all P < 0.0001). Of those who received a transplant after HCC (n = 488), only 5% were related to NAFLD-HCC. In multivariate analysis, NAFLD increased the risk of 1-year mortality (OR, 1.21; 95% CI: 1.01-1.45). Additionally, older age, lower income, unstaged HCC increased risk of 1-year mortality while receiving a liver transplant (LT), and having localized tumor stage were protective (all P < 0.05).NAFLD is becoming a major cause of HCC in the United States. NAFLD HCC is associated with shorter survival time, more advanced tumor stage, and lower possibility of receiving a LT.
Ultrasound evaluation of mediastinal lymphadenopathy in patients with sarcoidosis
Authors: Tim O. Hirche, Herbert Hirche, Xin-Wu Cui, Thomas O. Wagner, Christoph F. Dietrich
Journal: European Respiratory Journal (2014)

Purpose: Mediastinal lymphadenopathy is a typical feature of pulmonary sarcoidosis and an important parameter for diagnosis and follow-up. The present feasibility study is the first to elucidate the role of transthoracic mediastinal sonography for evaluation and staging of lymphadenopathy in patients with sarcoidosis.  Methods: 50 patients with sarcoidosis were subjected to high-definition mediastinal ultrasound. The sonographic lymph node status was compared with the radiologic staging – the prevailing gold standard.  Results: Mediastinal regions and landmarks could reliably be assessed by ultrasound in 45/50 (90%) of sarcoidosis patients. Lymphadenopathy was sonographically documented in 29/50 (58%) of the patients (sensitivity 89%, specificity 76%, PPV 86%, NPV 81%, accuracy 84%). There was a marked concordance between sonographic confirmation of lymphadenopathy and radiologic staging (k=0.67, p  Conclusion: Transthoracic sonography qualifies for the demonstration of the mediastinal regions and lymphadenopathy in patients with sarcoidosis. The procedure is facilitated by frequent and distinct mediastinal lymph node enlargement due to sarcoidosis. It will take prospective studies to find out whether mediastinal sonography adds value to conventional radiologic staging and provides a clinically advantage, particularly in the follow-up of patients with sarcoidosis.
P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil.
Authors: T P Miller, T M Grogan, W S Dalton, C M Spier, R J Scheper, S E Salmon
Journal: Journal of Clinical Oncology (1991)

P-glycoprotein is a transmembrane protein thought to function as an efflux pump to detoxify cells. It is associated with multidrug resistance in laboratory systems and has recently been found in human tumors associated with in vitro and clinical drug resistance. We used an immunohistochemical method employing two monoclonal antibodies, JSB-1 and C-219, to detect expression of P-glycoprotein in lymphoma patients. One of 42 newly diagnosed and untreated lymphoma patients (2%) and seven of 11 previously treated and drug-resistant patients (64%) had detectable levels of P-glycoprotein (P less than .001). Based on prior reports suggesting that verapamil sensitizes drug-resistant cancer cells to chemotherapy by competitive inhibition of the P-glycoprotein, we tested the efficacy of verapamil as a chemosensitizer in 18 patients with drug-refractory disease. All patients had previously failed or relapsed within 3 months of a doxorubicin-vincristine-containing drug regimen. Patients received day-1 cyclophosphamide, and 4-day continuous infusion doxorubicin and vincristine and oral dexamethasone (CVAD). CVAD was combined with 5-day continuous infusion verapamil given at maximally tolerated dose. Overall, 13 of 18 patients (72%) responded to treatment including five complete remissions (CRs; 28%). The median duration of response was 200 days and median survival was 242 days. The dose-limiting toxicity of the verapamil infusion was temporary cardiac dysfunction including hypotension, congestive heart failure, and cardiac arrhythmia. We conclude that the P-glycoprotein is uncommonly expressed in untreated lymphomas and frequently expressed in clinically drug-resistant disease, and that chemotherapy using CVAD plus maximally tolerated doses of verapamil results in a high response rate in patients carefully selected for clinical drug resistance.
Abstract 4220: A cell-penetrating nucleolytic lupus autoantibody damages DNA and is toxic to BRCA2-deficient cancer cells
Authors: Philip W. Noble, Melissa R. Young, Richard H. Weisbart, James E. Hansen
Journal: Cancer Research (2014)

Abstract Identification of therapeutic agents that are more toxic to malignant cells than normal cells is a key goal in cancer research. Many tumor cells harbor genetic defects that distinguish them from normal cells, and some of these defects have the potential to be exploited in the development of targeted therapies for cancer. Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging. A subset of lupus autoantibodies is associated with nucleolytic activity, and some of these antibodies are capable of nuclear penetration. We hypothesized that such antibodies might be capable of damaging DNA in cell nuclei and therefore have potential as therapeutic agents targeted towards DNA repair-deficient malignancies, such as tumors that are BRCA2-deficient. To test this hypothesis we screened a panel of cell-penetrating lupus autoantibodies for nucleolytic activity, and we identified 5C6 as an antibody of interest. 5C6 catalyzes degradation of single and double-stranded DNA in vitro and induces phospho-H2AX formation in BRCA2-deficient cells. When tested on a matched pair of BRCA2-proficient and deficient cancer cells, 5C6 selectively suppressed the growth of and was significantly more toxic to the BRCA2-deficient cells. These findings demonstrate the potential utility of 5C6 in targeted therapy for DNA repair-deficient malignancies and strengthen the rationale for studies of additional lupus autoantibodies in order to identify the best candidates for development as therapeutic agents. In addition, the toxicity of 5C6 for BRCA2-deficient cells provides further support for the hypothesis that some lupus autoantibodies contribute to the unusual cancer risk profile associated with systemic lupus erythematosus. Citation Format: Philip W. Noble, Melissa R. Young, Richard H. Weisbart, James E. Hansen. A cell-penetrating nucleolytic lupus autoantibody damages DNA and is toxic to BRCA2-deficient cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4220. doi:10.1158/1538-7445.AM2014-4220
Clinical and epidemiological characterization of a lymphogranuloma venereum outbreak in Madrid, Spain: co-circulation of two variants
Authors: M. Rodríguez-Domínguez, T. Puerta, B. Menéndez, J.M. González-Alba, C. Rodríguez, T. Hellín, M. Vera, F.J. González-Sainz, P. Clavo, M. Villa, R. Cantón, J. Del Romero, J.C. Galán
Journal: Clinical Microbiology and Infection (2013)
what's in a heuristic?
Authors: ulrike hahn, john-mark frost, greg maio
Journal: Behavioral and Brain Sciences (2005)

the term “moral heuristic” as used by sunstein seeks to bring together various traditions. however, there are significant differences between uses of the term “heuristic” in the cognitive and the social psychological research, and these differences are accompanied by very distinct evidential criteria. we suggest the term “moral heuristic” should refer to processes, which means that further evidence is required.
Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin.
Authors: H Xiao, M Mazumdar, D F Bajorin, M Sarosdy, V Vlamis, J Spicer, J Ferrara, G J Bosl, R J Motzer
Journal: Journal of Clinical Oncology (1997)

PURPOSE To assess the durability of response and overall survival for patients with good-risk metastatic germ cell tumors (GCT) treated with four cycles of etoposide and cisplatin (EP). PATIENTS AND METHODS Two hundred fourteen patients treated with EP on two consecutive randomized trials for good-risk metastatic GCT were the subject of this retrospective study. The response to therapy, relapse and survival status, and results of salvage therapy are reported. RESULTS One hundred ninety-five patients (91%) achieved a complete response (CR). This included 182 patients (85%) who achieved a CR to chemotherapy alone and 13 patients (6%) who achieved a CR to chemotherapy plus surgical resection of viable GCT. Seventeen patients (9%) have relapsed from CR. The median time to relapse was 10 months, and the longest duration from treatment to relapse was 36 months in a patient who received three of four planned courses of therapy. Eight patients who either achieved an incomplete response (IR) or relapsed were rendered continuously disease-free by salvage therapy and are alive. One hundred eighty-three patients (86%) are alive at a median follow-up of 7.6 years. CONCLUSION Four cycles of EP constitute effective therapy and can be offered to patients with good-risk GCT. In patients with intermediate- and poor-risk GCT, clinical trials remain a priority to identify more effective treatment.
Treatment of disseminated Mycobacterium simiae infection in AIDS
Authors: Marie-Pierre Steineur, André Boibieux, Thierry Zenone, Gilles Chaumentin, Bénédicte Contamin, Bénédicte Druel, Sylvestre Tigaud, Véronique Vincent, Dominique Peyramond
Journal: Clinical Microbiology and Infection (1997)
Impact of postoperative radiation therapy and other perioperative factors on outcome after orthopedic stabilization of impending or pathologic fractures due to metastatic disease.
Authors: P W Townsend, H G Rosenthal, S R Smalley, S C Cozad, R E Hassanein
Journal: Journal of Clinical Oncology (1994)

PURPOSE AND METHODS We reviewed 64 orthopedic stabilization procedures in 60 consecutive patients diagnosed with metastatic disease to previously unirradiated femurs, acetabula, and humeri with pathologic or impending pathologic fracture. Thirty-five patients who received adjuvant postoperative radiation therapy were compared with 29 patients who were treated with surgery alone. Many potential perioperative and tumor prognostic variables were evaluated. RESULTS On univariate analysis, surgery plus radiation therapy and prefracture functional status were the only significant predictors of patients who achieved normal use of the extremity (with or without pain) after surgery; on Cox multivariate analysis, only postoperative radiation therapy was significant (P = .02). Surgery-related factors such as use of methylmethacrylate, location of fracture, and type of surgery were not associated with improved functional status. The estimated probability of achieving normal use of the extremity (with or without pain) any time was 53% for postoperative radiation therapy versus 11.5% for surgery alone (P &lt; .01). Second orthopedic procedures to the same site were more frequent in the group that received surgery alone. The actuarial median survival duration of the surgery-alone group was 3.3 months, compared with 12.4 months for the postoperative radiation therapy group (P = .02). CONCLUSION While this study is limited by possible unaccountable selection biases, only postoperative radiation therapy was associated with patients regaining normal use of their extremity (with or without pain) and undergoing fewer reoperations to the same site. The improved overall survival associated with postoperative radiation therapy may represent selection bias.
Depression and posttraumatic stress disorder in Southeast Asian refugees
Authors: J Kroll, M Habenicht, T Mackenzie, M Yang, S Chan, T Vang, T Nguyen, M Ly, B Phommasouvanh, H Nguyen
Journal: American Journal of Psychiatry (1989)

The authors report on 404 Southeast Asian refugees seen at a community clinic. Approximately three-quarters of these patients met DSM-III criteria for major depressive episode, and 14% had posttraumatic stress disorder. Complaints of pain and sleep disturbances were the predominant presenting symptoms. Most of the men were married, but more than 40% of the women were widowed. Between 15% and 30% of the patients reported specific traumatic experiences either in their homeland or during their escape. Widowhood and such traumatic experiences were positively correlated with more symptoms of depression and anxiety.
Heterogeneity of blood flow and metabolism in exercising normal human muscle assessed by near infrared spectroscopy
Authors: Ioannis Vogiatzis, Helmut Habazettl, Zafeiris Louvaris, Vasileios Andrianopoulos, Harrieth Wagner, Spyros Zakynthinos, Peter Wagner
Journal: European Respiratory Journal (2014)

We used near-infrared spectroscopy (NIRS) to measure the regional distribution of blood flow and VO 2  in six trained cyclists at rest and during constant load exercise (unloaded pedaling, 20%, 50% and 80% of peak watts) in both normoxia and acute hypoxia (FIO 2 =0.12). From each of six optodes on the skin over the upper, middle and lower vastus lateralis, we recorded: a) indocyanine green dye (ICG) inflow after intravenous injection to measure blood flow (Q), and b) fractional tissue O 2  saturation (StO 2 ). Varying both exercise intensity and FIO 2  provided a (directly measured) femoral venous O 2  saturation (SfvO 2 ) range of about 10 to 70%, and a correspondingly wide range in StO 2 . A linear relationship was found between mean Q-weighted StO 2  over the 6 optodes and SfvO 2  in each subject. We used this relationship to compute local muscle venous blood O 2  saturation from StO 2  recorded at each optode, from which local VO 2 /Q ratios could be calculated by the Fick principle. Multiplying regional VO 2 /Q by Q yielded the corresponding local VO 2 . Assuming that the six optodes adequately surveyed the extent of heterogeneity, which must be tested in the future, relative dispersion of both Q and VO 2  was about 0.5 under all conditions, while that for VO 2 /Q was minimal (only about 0.1), indicating in fit young subjects: a) a strong capacity to regulate blood flow according to regional metabolic need from rest to heavy exercise in both normoxia and hypoxia, and b) a likely minimal impact of heterogeneity on muscle O 2  availability. Future application of this novel approach should clarify the extent and importance of heterogeneity in muscle of patients with chronic lung diseases.
Abstract 32: Cardiac Arrest: Who Goes to the Catheterization Lab?
Authors: Kalie Y Kebed, Robert S Schwartz, Marc C Newell, Joseph A Browning, Scott W Sharkey, Robert G Hauser, Barbara T Unger, Victoria R Pink, Wesley R Pedersen, Ivan J Chavez, Yale L Wang, Michael R Mooney
Journal: Circulation (2011)

Introduction: Therapeutic hypothermia (TH) is neuroprotective and increases survival in resuscitated cardiac arrest patients. Approximately 70% of sudden cardiac deaths are caused by coronary heart disease. For patients requiring angiography/PCI, TH can occur simultaneously. Methods: “Cool It” is a comprehensive TH protocol integrated into a regional STEMI network. From Feb 2006 to July 2010, 192 consecutive cardiac arrest patients who remained unresponsive following return of spontaneous circulation were enrolled in the Cool It protocol. Those patients with suspicion for ischemic etiology or evidence of STEMI were transferred directly to the cath lab. Results: On the 192 patients, angiogram was performed in 144 (75.0%). Patients sent for angiography had higher prevalence of initial rhythm VF/VT 116 (80.6%) vs. 19 (39.6%), cardiogenic shock 66 (45.8%) vs. 11 (22.9%), and ST elevation 54 (37.5%) vs. 1 (2.1%) than the 48 patients not undergoing angiography. PCI was performed in 73 (50.7% of patients undergoing angiogram, 38.0% all patients). Of these 73 patients, 64 (87.7%) had initial rhythm VF/VT, 38 (52.1%) were in cardiogenic shock, and 39 (53.4%) had ST elevation. Identified culprit arteries were LAD n=30 (41.1%), RCA n=24 (32.9%), CMX n=12 (16.4%), left main n=4 (5.5%), and none n=3 (4.1%). Mean pre-PCI TIMI flow was 1.36, and post-PCI TIMI flow was 2.91. BMS was used in 31 (42.5%), DES in 40 (54.8%), and one had balloon angioplasty only. Three were referred for CABG. Survival to hospital discharge was 43/73 (58.9%), and survival with favorable neurologic outcome (cerebral performance category 1 or 2) was 39/73 (53.4%). Patients who underwent angiography but did not receive PCI had the similar outcomes: survival was 46/71 (64.8%) and favorable neurologic outcome was seen in 44/71 (62.0%). Patients who did not undergo angiography had the poorest outcome: survival was 11/48 (22.9%) and with favorable neurologic outcome was seen in 9/48 (18.8%). Conclusion: The majority of unresponsive cardiac arrest survivors underwent angiography. Patients who underwent angiography with PCI had the similar outcomes to those with angiography alone. Favorable baseline patient characteristics appear to account for the improved outcomes in the angiography group.