tbuckley/cabot-search huggingface dataset:
Use of Restrictive Transfusion in Abdominal Surgery
Authors: Danny Chu
Journal: JAMA Surgery (2015)

Ejaz et al1 elegantly demonstrated in a single-institution study that significant monetary savings may be realized if surgeons were to adhere to a restrictive transfusion policy based on concrete intraoperative and postoperative hemoglobin values. There is little doubt that blood transfusion exposes patients to potential risks of bloodborne pathogens.2 Studies have also demonstrated worse short-term outcomes attributable to blood transfusion itself in critically ill patients.3 Recently, a multicenter, prospective, randomized clinical trial demonstrated no long-term mortality difference between liberal and restrictive transfusion strategies.4 In light of the current controversy and changing climate of health care reform, Ejaz and colleagues are to be commended for spearheading this timely and provocative study. However, many such studies are retrospective in nature, using administrative databases, and have thus suffered from selection bias and lack of clinical granularity.While the transfusion trigger usinghemoglobin levelsmayguide theneed for transfusion, these guidelines should be takenwith some caution and surgeons must use all clinical data to make the final determination on the need for transfusion. At the same time, liberal transfusion strategies based solely on relatively lowhemoglobin levels in completely asymptomatic healthy patients may expose them to unnecessary risks and possibly worse outcomes. Because it is nearly impossible to design a prospective randomizedclinical trial of blood transfusion triggers incorporating all possible clinical scenarios owing to ethical concerns, surgeons should carefullyweighall the risks and benefits of blood transfusionguidedbyevidenceanduse their best clinical judgment. Ultimately, evidence-basedmedicine should complement, not replace, the art of medicine.
Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral-blood stem-cell transplantation: a prospective, randomized trial.
Authors: T R Klumpp, K F Mangan, S L Goldberg, E S Pearlman, J S Macdonald
Journal: Journal of Clinical Oncology (1995)

PURPOSE It is well-established that the infusion of hematopoietic growth factors (HGF) accelerates neutrophil recovery in patients undergoing high-dose therapy followed by autologous bone marrow infusion. In addition, there is evidence that the infusion of autologous peripheral-blood stem cells (PBSC) accelerates engraftment in comparison to patients who receive bone marrow alone. However, few data are available regarding the ability of HGF to accelerate engraftment further in patients who receive PBSC following high-dose therapy. PATIENTS AND METHODS Forty-one patients undergoing high-dose therapy followed by infusion of autologous PBSC with or without bone marrow were randomized to receive granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg/d beginning on day + 1 following transplant or standard posttransplant supportive care without HGF. RESULTS The median time to a neutrophil count &gt; or = 500/microL was 10.5 days in the G-CSF group versus 16 days in the control group (P = .0001). G-CSF was associated with statistically significant reductions in the time to neutrophil engraftment among patients who received PBSC alone (11 v 17 days, P = .0003) and in patients who received PBSC in conjunction with bone marrow (10 v 14 days, P = .02). The median duration of posttransplant hospitalization (18 v 24 days, P = .002) and the median number of days on nonprophylactic antibiotics (11 v 15, P = .03) were also significantly reduced. CONCLUSION Administration of G-CSF in the posttransplant period accelerates the rate of neutrophil engraftment, shortens the duration of hospitalization, and reduces the number of days on nonprophylactic antibiotics in patients who receive autologous PBSC with or without autologous bone marrow following high-dose therapy.
Optimizing Systemic Therapy for Bladder Cancer
Authors: Sumanta K. Pal, Matthew I. Milowsky, Elizabeth R. Plimack
Journal: Journal of the National Comprehensive Cancer Network (2013)

Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.
Phase I trial of carboplatin and infusional cyclosporin in advanced malignancy.
Authors: R J Morgan, K Margolin, J Raschko, S Akman, L Leong, G Somlo, K Scanlon, C Ahn, M Carroll, J H Doroshow
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine the maximal-tolerated dose (MTD) of infusional cyclosporine (CSA) with fixed-dose carboplatin (CBDCA). PATIENTS AND METHODS Clonogenic cytotoxicity assays were performed to assess the effect of CSA on reversal of resistance to CBDCA. The phase I study was performed in three phases. In phases 1 and 2, escalating-dose CSA (5, 7.5, 8.8, or 9.5 mg/kg/d) with fixed-dose CBDCA 300 or 250 mg/m2 were administered. Phase 3 required an initial cycle of CBDCA 250 mg/m2 alone, followed by combination therapy with CBDCA 250 mg/m2 and CSA (8.8, 9.5, or 10.0 mg/kg/d). RESULTS Preincubation of platinum-resistant A2780 human ovarian cancer cells with CSA 2 micrograms/mL significantly enhanced CBDCA cytotoxicity in clonogenic assays. Fifty-one patients received 130 courses of therapy. The phase 1 MTD was thrombocytopenia (CSA 7.5 mg/kg/d and CBDCA 300 mg/m2) attributable to the effects of CBDCA alone. The phase 2 MTD was reversible nephrotoxicity (serum creatinine elevations to 3.6 and 4.4 mg/dL) and neutropenia (CSA 9.5 mg/kg/d and CBDCA 250 mg/m2). In phase 3, headache was observed in five patients and hypertension in one patient at CSA 10 mg/kg/d. The expected change in platelet count predicted for CBDCA alone was compared with the actual change; no excessive thrombocytopenia was observed with addition of CSA. Steady-state CSA levels of 2 micrograms/mL capable of reversing platinum resistance in vitro were observed. Four objective responses were observed. CONCLUSION CSA is effective in reversing CBDCA resistance in A2780 ovarian cancer cells. Short-term infusions of CSA &lt; or = 8.8 mg/kg/d in combination with CBDCA are well-tolerated for heavily pretreated patients and result in CSA levels known to reverse CBDCA resistance in vitro.
Serum vitamin D, magnesium and calcium on lung function and QoL in COPD: A cross-sectional study
Authors: Sarah Hashim Ali Hussein, Lars Peter Nielsen, Mette Konow Bogebjerg Dolberg, Ronald Dahl
Journal: European Respiratory Journal (2014)

Background:  Serum vitamin D-, magnesium- and calcium deficiency may be associated with an increased exacerbation risk in chronic obstructive pulmonary disease (COPD). However, associations with other aspects of COPD, e.g. lung function and quality of life (QoL), have been studied less extensively.   Aim:  To investigate serum vitamin D, magnesium and calcium in COPD and the associations between these three parameters and FEV 1  and QoL.   Methods:  FEV 1  and serum vitamin D, magnesium and calcium were measured during summer 2012. Generic and health related QoL were characterized.   Results:  This cross-sectional study included 143 patients with COPD. Women had a significantly higher serum vitamin D than men (P=0.0028), and 27 % of participants were vitamin D insufficient.  Lung function, measured as FEV 1 , was not correlated with serum vitamin D3, magnesium or calcium in COPD. Magnesium insufficiency group reported significantly impaired mobility, usual activitis, pain/discomfort and COPD-related QoL. Vitamin D and calcium were not associated with QoL.   Discussion:  Serum levels of vitamin D, magnesium and calcium were not related to FEV 1 . Most patients in this study were serum vitamin D-, magnesium- and calcium sufficient. Women had higher serum vitamin D than men.  Serum magnesium was associated with QoL in COPD. No associations were seen between QoL and serum vitamin D and calcium.  Prospective randomized studies are needed to substantiate these findings.
Treatment of intractable hiccups with intramuscular haloperidol
Authors: T. J. Ives, M. F. Fleming, C. W. Weart, D. Bloch
Journal: American Journal of Psychiatry (1985)

Two patients with intractable hiccups were treated with intramuscular haloperidol; remission occurred within 1 hour. With its rapid action and low incidence of adverse effects, intramuscular haloperidol should be considered a therapeutic alternative in the treatment of intractable hiccups.
Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI. In vivo evidence for a role of factor XI as an anti-fibrinolytic factor.
Authors: M C Minnema, P W Friederich, M Levi, P A von dem Borne, L O Mosnier, J C Meijers, B J Biemond, C E Hack, B N Bouma, H ten Cate
Journal: Journal of Clinical Investigation (1998)

Recent in vitro studies have shown that fibrinolytic activity may be attenuated by a thrombin-activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin, generated via the intrinsic pathway of coagulation in a factor XI-dependent way. Thus factor XI may play a role in the regulation of endogenous fibrinolysis. The aim of this study was to investigate the effect of in vivo inhibition of factor XI and TAFI in an experimental thrombosis model in rabbits. Incorporation of anti-factor XI antibodies in jugular vein thrombi resulted in an almost twofold increase in endogenous thrombolysis compared with a control antibody. A similar effect was observed when the anti-factor XI antibody was administered systemically. Inhibition of TAFI activity also resulted in a twofold increase in clot lysis whereas inhibition of both factor XI and TAFI activity had no additional effect. Thus, we provide the first in vivo evidence for enhanced thrombolysis through inhibition of clotting factor XI, demonstrating a novel role for the intrinsic pathway of coagulation. Furthermore we demonstrate that inhibition of TAFI had a similar effect on thrombolysis. We postulate that inhibition of factor XI activity enhances thrombolysis because of diminished indirect activation of TAFI.
Antibiotic Allergy
Authors: Rebecca S. Gruchalla, Munir Pirmohamed
Journal: New England Journal of Medicine (2006)

A 55-year-old woman presents to the hospital with cellulitis. She reports a history of urticaria 30 years earlier associated with taking penicillin for a respiratory infection. Should cephalosporins be avoided? More generally, how should patients with a history of antibiotic allergy be evaluated and treated?
Associations between bronchiolitis and respiratory outcomes at 18 years in the PIAF birth cohort
Authors: Desmond Cox, David Mullane, Steven Turner, Guigeng Zhang, Catherine Hayden, Jack Goldblatt, Lou Landau, Peter Le Souef
Journal: European Respiratory Journal (2011)

Introduction:  The Perth infant asthma follow-up (PIAF) study is a birth cohort of unselected subjects who have undergone longitudinal respiratory assessments from birth to 18 years. We previously reported that individuals with bronchiolitis had reduced lung function and increased wheeze in later childhood. We also found that there was reduction in lung function in individuals both before bronchiolitis and at 11 years of age.   Aim:  To investigate the relationship between bronchiolitis and respiratory outcomes in early adulthood.   Methods:  Children had prospective assessments performed at 1, 6 and 12 months and again at 6, 11 and 18 years. They included a questionnaire, lung function, airway responsiveness and skin prick testing.   Results:  The initial recruitment population was 253. We followed up 150 children at 18 years, of which 20 had current asthma and 13 had persistent asthma. There were 16 cases of confirmed bronchiolitis previously identified. We found a significant association between bronchiolitis and “ever being diagnosed with asthma” (p=0.01, OR 7.35, 95%CI 1.5 to 35.0) and “ever being diagnosed with asthma” (p=0.03, OR 5.1, 95%CI 1.1 to 23.2) at 18 years. Children diagnosed with bronchiolitis had a mean reduced FEF of 16% (95% CI;-1.4 to -0.8, p=0.03) when compared to rest of the cohort at 18 years.   Conclusion:  These data confirm that the reduced flows at 1 month and 11 years were not fortuitous and suggests that this group have airways that predisposed to bronchiolitis in infancy, increased asthma in childhood, no increase in active symptoms in early adult life but will need follow up to see if they are prone to conditions such as COPD or tobacco related lung disease.
Detection of FGF15 in Plasma by Stable Isotope Standards and Capture by Anti-peptide Antibodies and Targeted Mass Spectrometry
Authors: Takeshi Katafuchi, Daria Esterházy, Andrew Lemoff, Xunshan Ding, Varun Sondhi, Steven A. Kliewer, Hamid Mirzaei, David J. Mangelsdorf
Journal: Cell Metabolism (2015)
Predictive value of the Theros Breast Cancer Index (TBCI) for distant recurrence and overall survival (OS) in comparison to Adjuvant! Online and clinicopathologic characteristics in women with lymph node (LN)-negative, ER-positive breast cancer (BCa).
Authors: R. C. Jankowitz, M. Chivukula, X. Ma, M. G. Erlander, L. L. Mock, L. S. Mazur, H. Li, R. Salunga, S. Sereika, A. Brufsky
Journal: Journal of Clinical Oncology (2010)

10582 Background: Gene expression profiles may have higher predictive power for relapse over traditional clinicopathologic prognostic factors. TBCI combines the 2-gene index HOXB13:IL17BR and a 5-gene Molecular Grade Index (MGI) and is a continuous predictor of individual risk of distant recurrence. Adjuvant! Online (AO), a web-based actuarial tool, predicts 10-year BCa recurrence and OS based on clinical patient and tumor characteristics. We sought to determine if TBCI provided additional predictive power for recurrence and OS over AO. Methods: This was a single-institution, retrospective study.Tumor tissue from 262 patients with ER(+), LN(-) BCa with at least 10 year follow up was assessed by a pathologist (for verification of histologic grade and ER status) and then evaluated using the TBCI assay. AO was used to predict risk of relapse for each patient. Results were correlated to distant recurrence and overall survival. Statistical analysis to compare prognostic utility of TBCI and AO was conducted according to a pre-specified analysis plan using pre-determined models and cutoffs. Results: In univariate analysis, both TBCI and AO were highly significant predictors of recurrence and death, and the association remained significant after adjusting for other standard variables (age, tumor size, and grade). In a multivariate model of TBCI and AO together, TBCI predicted recurrence with a hazard ratio (HR) of 2.47 [1.51-4.03] (p < 0.001), and AO predicted recurrence with an HR of 1.44 [1.13-1.82] (p < 0.01).TBCI predicted overall survival with a hazard ratio (HR) of 2.82 [1.694-4.708] (p < 0.0001), and AO predicted survival with a HR of 1.24 [0.950-1.630] (p = 0.11). Conclusions: TBCI predicted BCa recurrence and OS more accurately than AO and traditional clinical and pathologic features. TBCI and AO both retained predictive significance in a multivariate analysis of recurrence and death, indicating that they can provide complementary information. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration bioTheranostics bioTheranostics bioTheranostics
MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia
Authors: Courtney L. Jones, Christy M. Gearheart, Susan Fosmire, Cristina Delgado-Martin, Nikki A. Evensen, Karen Bride, Angela J. Waanders, Faye Pais, Jinhua Wang, Teena Bhatla, Danielle S. Bitterman, Simone R. de Rijk, Wallace Bourgeois, Smita Dandekar, Eugene Park, Tamara M. Burleson, Pillai Pallavi Madhusoodhan, David T. Teachey, Elizabeth A. Raetz, Michelle L. Hermiston, Markus Müschen, Mignon L. Loh, Stephen P. Hunger, Jinghui Zhang, Michael J. Garabedian, Christopher C. Porter, William L. Carroll
Journal: Blood (2015)
The use of dermatoscopy to monitor therapeutic response of Bowen disease: a dermatoscopic pathological study
Authors: J.‐H. Mun, J.‐M. Park, M. Song, S.‐W. Jwa, H.‐S. Kim, H.‐C. Ko, B.‐S Kim, M.‐B. Kim
Journal: British Journal of Dermatology (2012)

Dermatoscopy is a noninvasive technique that can be helpful in the diagnosis of pigmented and nonpigmented skin tumours. The dermatoscopic evaluation of Bowen disease (BD) improves diagnostic accuracy.To evaluate the usefulness of dermatoscopy as a tool for assessing responses to therapy and recurrence of BD.Patients with histopathologically diagnosed BD were prospectively enrolled. In all lesions, 3 months after the end of treatment (photodynamic therapy or 5% imiquimod cream), dermatoscopic and histopathological examinations were repeated to evaluate and correlate changes in dermatoscopic features and histopathological results. Cured lesions were monitored using dermatoscopy during the follow-up period.A total of 23 patients with 29 histopathologically diagnosed BD lesions were included in this study. After treatment, dermatoscopic examination revealed the disappearance of pre-existing vascular structures in 16 lesions, and remaining vascular structures in 13 lesions. Histopathological evaluation of the treated lesions showed remnant intraepithelial neoplasms and increased dermal vascularity in lesions with persistent dermatoscopic vascular structures. However, normal epidermis and decreased dermal vascularity were observed in all but one of the lesions without previous dermatoscopic vascular structures. During the follow-up period, one lesion showed reappearance of previous vascular structures on dermatoscopy 9 months after treatment. Histopathological examination confirmed the recurrence of BD.Our study demonstrates that the persistence of dermatoscopic vascular structures of BD appears to be associated with residual disease, and disappearance of vascular structures suggests that the disease has been cured. In addition, reappearance of previous dermatoscopic vascular structures indicates the recurrence of BD. Therefore, we suggest that dermatoscopy can be a useful, reliable and noninvasive tool in the therapeutic follow-up of BD.
Professionals should not collude with abusive systems
Authors: J. Menage
Journal: BMJ (1995)

EDITOR,--J A Black and G D Debelle do not go far enough in their article on female genital mutilation.1 They state, “genital mutilation is a form of child abuse, though this term should not be used when discussing the procedure with families as it would be greatly resented.” This suggests that the feelings of the families and doctors should be given precedence over the feelings of the child(ren) being …
Cerebral infarct and adult respiratory distress syndrome in a patient with postanginal sepsis
Authors: M.N. Marangos, D.A. Fnchs-Ertman, H.P. Konrea, K.J. Menrer, P.A. Lerwick, S.H. Zimmerman, A.J. Valenti
Journal: Clinical Microbiology and Infection (2000)
Reform of medical regulation is left off the Queen's speech for a second time
Authors: G. Iacobucci
Journal: BMJ (2015)

The General Medical Council (GMC) has said that it is “deeply disappointed” that the Queen’s speech did not include new legislation to change the regulation of healthcare professionals to give greater protection to patients.

The Law Commissions of the UK published draft legislation in 20141 to modernise current professional regulations and give regulators such as the GMC greater freedom to certificate the knowledge, skills, and competence of doctors in particular areas of practice.

In the wake of the PIP breast implant scandal and the review of cosmetic surgery by Bruce Keogh, NHS medical director,2 a law change could tighten current rules that allow …
Rectal Cancer after Pelvic Irradiation
Authors: M D Levitt, D M Millar, J O Stewart
Journal: Journal of the Royal Society of Medicine (1990)

During a 6 month period in 1988 five women were treated at Colchester General Hospital for carcinoma of the rectum, each more than 10 years after undergoing pelvic irradiation. Although irradiation has not been proven to induce human colorectal cancer, considerable circumstantial and experimental evidence supports this belief. Features suggestive of radiation-induced colorectal cancer are the presence of radiation-damaged bowel adjacent to the carcinoma and a mucus-secreting ('colloid') histological pattern. The increasing number of women being exposed to rectal irradiation in the course of treatment of gynaecological malignancy may result in an increase in the incidence of radiation-induced rectal cancer. Awareness of this potential long-term complication is important when planning follow-up of patients subjected to pelvic radiotherapy.
Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors
Authors: Stuart A. Grossman, Susannah Ellsworth, Jian Campian, Aaron T. Wild, Joseph M. Herman, Dan Laheru, Malcolm Brock, Ani Balmanoukian, Xiaobu Ye
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: The immune system plays an important role in cancer surveillance and therapy. Chemoradiation can cause severe treatment-related lymphopenia (TRL) (<500 cells/mm3) that is associated with reduced survival. Materials and Methods: Data from 4 independent solid tumor studies on serial lymphocyte counts, prognostic factors, treatment, and survival were collected and analyzed. The data set included 297 patients with newly diagnosed malignant glioma (N=96), resected pancreatic cancer (N=53), unresectable pancreatic cancer (N=101), and non–small cell lung cancer (N=47). Results: Pretreatment lymphocyte counts were normal in 83% of the patient population, and no patient had severe baseline lymphopenia. Two months after initiating chemoradiation, 43% developed severe and persistent lymphopenia (P=.001). An increased risk for death was attributable to TRL in each cancer cohort (gliomas: hazard rate [HR], 1.8; 95% CI, 1.13–2.87; resected pancreas: HR, 2.2; 95% CI, 1.17–4.12; unresected pancreas: HR, 2.9; 95% CI, 1.53–5.42; and lung: HR, 1.7; 95% CI, 0.8–3.61) and in the entire study population regardless of pathologic findings (HR, 2.1; 95% CI, 1.54–2.78; P<.0001). Severe TRL was observed in more than 40% of patients 2 months after initiating chemoradiation, regardless of histology or chemotherapy regimen, and was independently associated with shorter survival from tumor progression. Conclusions: Increased attention and research should be focused on the cause, prevention, and reversal of this unintended consequence of cancer treatment that seems to be related to survival in patients with solid tumors.
Abstract 825: Translocation of p27 to the Mitochondria Links Mitochondrial Energy Metabolism with Endothelial Cell Migration
Authors: Ioakim Spyridopoulos, Rudiger Popp, Vicente Andres, Stefanie Dimmeler, Judith Haendeler
Journal: Circulation (2006)

The migratory capacity of endothelial cells (EC) is a key prerequisite for the growth of new blood vessels during neovascularisation of ischemic and/or tumor tissues. Recently, mitochondria have be...