tbuckley/cabot-search huggingface dataset:
Targeting Host Complement C3a/C5a Receptors to Control of Acute Graft-Versus-Host Disease in Mice
Authors: Hung Nguyen, Jessica Lauren Heinrichs, Jianing Fu, Yongxia Wu, David Bastian, Steven Schutt, Anusara Daenthanasanmak, Mohammmed Dany, Chen Liu, David Fairlie, Stephen Tomlinson, Xue-Zhong Yu
Journal: Blood (2015)
Challenging the medical student in a psychiatry clerkship
Authors: L S Linet
Journal: American Journal of Psychiatry (1977)

Medical students sometimes view their rotation in psychiatry as a less-than-optimal experience. The author focuses on the often-heard reference to the psychiatric clerkship as a vacation and the adverse consequences of this attitude on learning. He emphasizes that the medical student can be given a substantial quantity and quality of responsibility without making the clerkship either aggressively overwhelming or disadained as unchallenging.
Preoperative Membranous Urethral Length Measurement and Continence Recovery Following Radical Prostatectomy: A Systematic Review and Meta-analysis
Authors: Sean F. Mungovan, Jaspreet S. Sandhu, Oguz Akin, Neil A. Smart, Petra L. Graham, Manish I. Patel
Journal: European Urology (2016)

Membranous urethral length (MUL) measured prior to radical prostatectomy (RP) has been identified as a factor that is associated with the recovery of continence following surgery. To undertake a systematic review and meta-analysis of all studies reporting the effect of MUL on the recovery of continence following RP. A comprehensive search of PubMed, EMBASE, and Scopus databases up to September 2015 was performed. Thirteen studies comprising one randomized controlled trial and 12 cohort studies were selected for inclusion. Four studies (1738 patients) that reported hazard ratio results. Every extra millimeter (mm) of MUL was associated with a faster return to continence (hazard ratio: 1.05; 95% confidence interval [CI]: 1.02–1.08, p < 0.001). Eleven studies (6993 patients) reported the OR (OR) for the return to continence at one or more postoperative time points. MUL had a significant positive effect on continence recovery at 3 mo (OR: 1.08, 95% CI: 1.03–1.14, p = 0.004), 6 mo (OR: 1.12, 95% CI: 1.09–1.15, p < 0.0001). and 12 mo (OR: 1.12, 95% CI: 1.03–1.22, p = 0.006) following surgery. After adjusting for repeated measurements over time and studies with overlapping data, all OR data combined indicated that every extra millimeter of MUL was associated with significantly greater odds for return to continence (OR: 1.09, 95% CI: 1.05–1.15, p < 0.001). A greater preoperative MUL is significantly and positively associated with a return to continence in men following RP. Magnetic resonance imaging measurement of MUL is recommended prior to RP. We examined the effect that the length of a section of the urethra (called the membranous urethra) had on the recovery of continence after radical prostatectomy surgery. Our results indicate that measuring the length of the membranous urethra via magnetic resonance imaging before surgery may be useful to predict a longer period of urinary incontinence after surgery, or to explain a delay in achieving continence after surgery.
Phase 1 Study of MLN8237, an Aurora KinaseA (AURKA) Inhibitor, Combined with Vorinostat, a Histone Deacetylase (HDAC) Inhibitor, in Lymphoid Malignancies
Authors: Tanya Siddiqi, Paul Frankel, Chris Ruel, Robert W Chen, Kevin R. Kelly, Joseph Tuscano, Leslie Popplewell, Stephen J. Forman, Richard Piekarz, Edward Newman
Journal: Blood (2014)
A Phase 3 Study Evaluating the Efficacy and Safety of Lenalidomide Combined with Melphalan and Prednisone In Patients ≥ 65 Years with Newly Diagnosed Multiple Myeloma (NDMM): Continuous Use of Lenalidomide Vs Fixed-Duration Regimens
Authors: Antonio Palumbo, Michel Delforge, John Catalano, Roman Hajek, Martin Kropff, Maria Teresa Petrucci, Zhinuan Yu, Lindsey Herbein, Jay M. Mei, Christian J. Jacques, Meletios A. Dimopoulos
Journal: Blood (2010)
Pan-Selectin Antagonist Rivipansel (GMI-1070) Reduces Soluble E-Selectin Levels While Improving Clinical Outcomes in SCD Vaso-Occlusive Crisis
Authors: Ted Wun, Marilyn J. Telen, Lakshmanan Krishnamurti, Timothy L. McCavit, Laura M DeCastro, Henry Flanner, Frans A. Kuypers, Sandra K. Larkin, Seungshin Rhee, John L. Magnani, Helen M. Thackray
Journal: Blood (2014)
A randomized phase III study of trabectedin (T) or dacarbazine (D) for the treatment of patients (pts) with advanced liposarcoma (LPS) or leiomyosarcoma (LMS).
Authors: George D. Demetri, Margaret von Mehren, Robin Lewis Jones, Martee Leigh Hensley, Scott Schuetze, Arthur P. Staddon, Mohammed M. Milhem, Anthony D. Elias, Kristen N. Ganjoo, Hussein Abdul-Hassan Tawbi, Brian Andrew Van Tine, Alexander I. Spira, Andrew Peter Dean, Nushmia Z. Khokhar, Youn Choi Park, Roland Elmar Knoblauch, Trilok V. Parekh, Robert G. Maki, Shreyaskumar Patel
Journal: Journal of Clinical Oncology (2015)

10503 Background: This phase III multicenter trial compared T with D in pts with advanced LPS or LMS previously treated with an anthracycline and at least one additional systemic therapy. Methods: Pts were randomized to T or D in a 2:1 ratio. Dosing of T and D were q 3 wks IV infusion: T (1.5 mg/m2 over 24 hr) vs D (1 g/m2 over 20-120 min). The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), time to progression (TTP), objective response rate (ORR), duration of response (DOR), symptom severity and safety. Cross-over to T after disease progression (PD) on D was not allowed until revision after this planned interim analysis (IA) of OS (50% events). The study is ongoing for final OS. Final results of secondary endpoints are presented. Results: The IA included 518 pts (T = 345, D = 173), 73% with LMS and 27% with LPS. Treatment with T resulted in a 45% reduction in the risk of PD or death compared with D (hazard ratio [HR] = 0.550; P < 0.0001; Median [M] 4.2 vs 1.5 months [mo], respectively), with benefit observed across all subgroups, and validated by independent radiologists audit. Other end points demonstrated improved efficacy of T: TTP (HR = 0.522, p < 0.0001; M = 4.2 vs 1.5 mo), clinical benefit rate (CR+PR+SD ≥ 18wks) (34.2% vs 18.5%; Odds Ratio[OR] = 2.291; p = 0.0002), ORR (9.9% vs 6.9%; OR = 1.467; p = 0.3269), DOR (HR=0.471, p = 0.1415; M = 6.5 vs 4.2 mo). The IA of OS (64% censored) demonstrated a 13% reduction in risk of death in T arm compared with D (HR = 0.872, p = 0.3741; M = 12.4 vs 12.9 mo). 34% of T and 17% of D pts received ≥ 6 cycles. The safety profiles were consistent with the well-characterized toxicities of both agents, with the most common grade 3-4 toxicities in T vs. D arm being ANC (40% vs 25%), platelets (19% vs 20%), increased ALT (29% vs 1%), and drug-related death (2.1% vs 0%). Patient-reported outcomes were similar across the arms, with low symptom scores during treatment. Conclusions: This phase III trial demonstrates improved disease control with T vs. D in advanced LPS and LMS, and confirms the acceptable benefit-risk profile of T from the prior randomized Phase 2 study (STS-201). T is a meaningful treatment option for pts with advanced LPS and LMS. Clinical trial information: NCT01343277.
Phase I/II study of lenvatinib (E7080), a multitargeted tyrosine kinase inhibitor, in patients (pts) with advanced hepatocellular carcinoma (HCC): Phase I results.
Authors: Shuichi Mitsunaga, Masafumi Ikeda, Hideki Ueno, Kohei Nakachi, Chigusa Morizane, Shunsuke Kondo, Satoshi Shimizu, Yasushi Kojima, Takuya Suzuki, Toshiyuki Tamai, James P. O'Brien, Takuji Okusaka
Journal: Journal of Clinical Oncology (2013)

231 Background: Lenvatinib is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFR-beta. Maximum tolerated dose (MTD) of lenvatinib for solid tumor pts was determined to be 25 mg once daily dosing (qd). The current study was planned to determined MTDs and pharmacokinetic profiles of lenvatinib in HCC pts with Child-Pugh grade (CP) A and B. Methods: Between Aug. 2009 and Nov. 2011, a total of 20 pts with advanced HCC were enrolled in phase I part (Ph I). Ph I consists of a standard dose escalation design in separate cohorts of CP-A (6 pts per cohort) and CP-B (3+3 pts). The initial dose level of lenvatinib for CP-A and for CP-B was 12 mg qd. Tumor response was assessed by RECIST 1.1. Results: Nine pts with CP-A and 11 pts with CP-B were enrolled and evaluable for safety and efficacy. Pt characteristics: median age: 63.5 years, Male: 85%, HBV: 35% / HCV: 45%. 1/6 pt in 12 mg qd and 2/3 pts in 16 mg qd experienced DLTs (fever/vomiting, hepatic encephalopathy and proteinuria) in the CP-A group. In the CP-B group 2/5 pts in 12 mg qd and 0/6 pt in 8 mg qd experienced DLTs (hepatic encephalopathy and AST increased/hyperbilirubinaemia/creatinine increased). The most common toxicities were hypertension (all grade (Gr):75%, Gr3:50%), diarrhea (all Gr:70%, Gr3:0%), anorexia (all Gr:65%, Gr3:0%), palmar-plantar erythrodysaesthesia syndrome (all Gr:65%, Gr3:5%), fatigue (all Gr:65%, Gr3:0%) and hyperbilirubinaemia (all Gr:50%, Gr3:15%). Confirmed partial responses were observed in 4 pts and stable disease were in 9 pts. Median time to progression was 3.7 mo. Following administration of 12 mg lenvatinib, trough plasma concentrations (Ctrough) of the CP-A (n=5), CP-B (n=2), and pts with other solid tumors were 49.7 ± 23.6 (mean ± standard deviation), 73.7 and 22.8 ± 9.8 ng/mL respectively. Conclusions: The MTD for lenvatinib in advanced HCC pts with CP-A and CP-B are 12 mg qd and 8 mg qd, respectively. Ctrough is substantially higher than in HCC pts than in pts with other solid tumors. Lenvatinib 12 mg qd in HCC pts with CP-A and 8 mg qd in HCC pts with CP-B were associated with manageable toxicity and preliminary evidence of antitumor activity. Clinical trial information: NCT00946153.
An Instrument for Gastric Biopsy of the Rhesus Monkey
Authors: K SETALA, P ERMALA, M SIURALA
Journal: JNCI Journal of the National Cancer Institute (1953)

An Instrument for Gastric Biopsy of the Rhesus Monkey Get access Kai Setälä, Kai Setälä Search for other works by this author on: Oxford Academic PubMed Google Scholar Pentti Ermala, Pentti Ermala Search for other works by this author on: Oxford Academic PubMed Google Scholar Max Siurala Max Siurala Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 14, Issue 1, August 1953, Pages 141–147, https://doi.org/10.1093/jnci/14.1.141 Published: 01 August 1953 Article history Received: 19 March 1953 Published: 01 August 1953
Safety Profile Of Bortezomib Impacts Survival Of Cardiac AL Amyloidosis
Authors: Zoé Van de Wyngaert, Greg Vanoutryve, Charles Herbaux, Guillemette Fouquet, Helene Demarquette, Sarah Bonnet, David Beauvais, Stéphanie Guidez, Nicolas Lamblin, Eric Hachulla, David Launay, Louis Terriou, Bénédicte Hivert, Mathieu Wemeau, Xavier Leleu
Journal: Blood (2013)
Hip morphology in elite golfers: asymmetry between lead and trail hips
Authors: Edward Dickenson, Philip O'Connor, Philip Robinson, Robert Campbell, Imran Ahmed, Miguel Fernandez, Roger Hawkes, Hutchinson Charles, Damian Griffin
Journal: British Journal of Sports Medicine (2016)

Aim During a golf swing, the lead hip (left hip in a right-handed player) rotates rapidly from external to internal rotation, while the opposite occurs in the trail hip. This study assessed the morphology and pathology of golfers’ hips comparing lead and trail hips. Methods A cohort of elite golfers were invited to undergo MRI of their hips. Hip morphology was evaluated by measuring acetabular depth (pincer shape=negative measure), femoral neck antetorsion (retrotorsion=negative measure) and α angles (cam morphology defined as α angle &gt;55° anteriorly) around the axis of the femoral neck. Consultant musculoskeletal radiologists determined the presence of intra-articular pathology. Results 55 players (mean age 28 years, 52 left hip lead) underwent MRI. No player had pincer morphology, 2 (3.6%) had femoral retrotorsion and 9 (16%) had cam morphology. 7 trail hips and 2 lead hips had cam morphology (p=0.026). Lead hip femoral neck antetorsion was 16.7° compared with 13.0° in the trail hip (p&lt;0.001). The α angles around the femoral neck were significantly lower in the lead compared with trail hips (p&lt;0.001), with the greatest difference noted in the anterosuperior portion of the head neck junction; 53° vs 58° (p&lt;0.001) and 43° vs 47° (p&lt;0.001). 37% of trail and 16% of lead hips (p=0.038) had labral tears. Conclusions Golfers’ lead and trail hips have different morphology. This is the first time side-to-side asymmetry of cam prevalence has been reported. The trail hip exhibited a higher prevalence of labral tears.
Prediction of Response to Treatment with Lenalidomide in Patients with Non-Del 5q Myelodysplastic Syndrome by Gene Expression Profiling Remains Difficult.
Authors: Wolf-Karsten Hofmann, Florian Nolte, Ouidad Benlasfer, Eckhard Thiel, Gerhard Ehninger, Uwe Platzbecker
Journal: Blood (2009)
Brain-computer interfaces in end-of-life decision-making
Authors: Walter Glannon
Journal: Brain-Computer Interfaces (2016)

Brain-computer interfaces (BCIs) may enable some patients with brain injuries preventing verbal or gestural communication to communicate through brain activity alone. Cognitive impairment in the minimally conscious state (MCS), however, would appear to preclude patients in this state from meeting the requirements of informed consent and decision-making about life-sustaining care. Yet some patients at the higher end of the MCS spectrum may have enough awareness to understand their condition, experience pleasure or pain and suffering and enough cognitive capacity to express wishes through a BCI to continue or end their experience. A weaker concept of informed consent and decisional capacity confirmed through a repeated and consistent pattern of affirmative or negative responses to questions about quality of life and artificial nutrition and hydration (ANH) may justify these responses as sufficiently informed decisions about care. Failure to take these responses as autonomous decisions may harm these patients by failing to respect their autonomy and act in their best interests. It could also be unfair to deny them the right to make these decisions just because they are unable to express them through ordinary means.
Preliminary results of a phase II trial with continuous intravenous infusion of rh-endostatin in combination with dacarbazine as the first-line therapy for metastatic acral melanoma.
Authors: Chuanliang Cui, Lu Si, Zhihong Chi, Xi Nan Sheng, Li Li Mao, Xuan Wang, Bixia Tang, BIN LIAN, Xieqiao Yan, Jun Guo
Journal: Journal of Clinical Oncology (2015)

e20087 Background: A phase II study has revealed that rh-Endostatin (Endostar) was effective, when combined with dacarbazine (DTIC), for metastatic melanoma patients (pts), especially for pts with acral melanoma. Preclinical data suggest that continuous infusion of endostatin is more potent than intermittent dosing. A phase II study is performed to evaluate the efficacy and safety of continuous intravenous infusion (CIV) of Endostar in combination with DTIC as 1stline therapy for pts with metastatic acral melanoma. Methods: Twenty treatment-naive pts with metastatic acral melanoma and without C-Kit/BRAF mutation were enrolled in this study. The efficacy and safety of DTIC (250 mg/m2 d1-5) plus Endostar CIV (Baxter infusion pump 2 ml/h; 7.5mg/m2/d or 15mg/m2/d d1-14) were evaluated. The regimens continued in a 28-day cycle until disease progression (PD) or intolerable toxicity occurred. The primary endpoint was progression free survival (PFS), and the secondary endpoints included disease control rate (DCR) and safety. Results: From Dec 2013 to Oct 2014, 10 pts were enrolled in 7.5mg/m2/d Endostar group (group A), and another 10 pts were enrolled in the 15mg/m2/d group (group B). In group A, M1a disease was 30%, M1b 50% and M1c 20%; In group B, M1a 20%, M1b 30% and M1c 50%. Mean treatment cycle was 3.1 (range: 1-6) in group A and 2.6 (range: 1-6) in group B. Until last follow-up in Jan. 2015, 9 pts achieved PD. The estimated mPFS was 3.0 months (95% CI: 0.86~5.14) in group A and 6.0 months in group B (95% CI: 1.69~10.31, P = 0.178, log-rank test). DCR in group B (80%; 8 SD and 2 PD) was higher than that in group A (50%; 5 SD and 5 PD) without statistical significance. This combination was well tolerated without grade 3-4 toxicity; the most common side effect was intermittent palpitation in group B (2/10), with sinus tachycardia but without ST-T change by ECG monitoring. Conclusions: Endostar administered by continuous infusion was safe, and 15mg/m2/d Endostar combining with DTIC might cause better estimated PFS and DCR than 7.5mg/m2/d Endostar plus DTIC in pts with metastatic acral melanoma. A controlled study with a larger sample size is still needed.
Chlorhexidine bathing to reduce CLABSI in hematopoietic stem cell transplant and hematologic malignancy patients.
Authors: Christina Reeber, Kelly Bailey, Carrie Nemec, Robert A. Salata, Kathleen Gonzalez
Journal: Journal of Clinical Oncology (2012)

119 Background: At University Hospitals Seidman Cancer Center (UHSCC), adult patients with hematologic malignancies (HM) and those undergoing hematopoietic stem cell transplant (HSCT) require a central venous catheter nearly 100% of the time. According to the National Health Safety Network (NSHN), for permanent and temporary line days, the pooled mean infection rate in 2009 was 3.5 and 4.1, respectively. Catheter-associated bloodstream infections (CLABSI) lead to increased morbidity, mortality, length of stay, and cost. At UHSCC, the CLABSI rate for patients on the HM service from August 2010 through August 2011 was 8.0. Methods: It has been demonstrated that the use of Chlorhexidine (CHG) wipes has decreased the CLABSI rate in ICU and long term care patients. We were unable to identify literature evidence or medical centers currently using CHG bathing wipes in their cancer patients, specifically HSCT. A quality improvement project on the effectiveness of CHG bathing on the HSCT and HM populations commenced on April 2, 2012, at UHSCC. This study is also monitoring skin integrity to determine if there are adverse effects. Patient satisfaction is also being assessed. Results: Early results demonstrate a reduction in overall CLABSI rate to 4.3%, and no vancomycin resistant enterococcus (VRE) infections were observed since early April. Adverse effects on skin integrity have not been noted. An unanticipated obstacle is related to the “culture of bathing.” Specifically, caregivers and patients often do not understanding the importance of daily bathing as a key clinical intervention despite repeated education. The team continues to investigate this issue. Conclusions: CHG bathing appears to be an effective, well-tolerated, and minimally invasive intervention in preventing CLABSI in severely immunocompromised cancer patients. Unanticipated obstacles to implementing daily bathing have been encountered and are being addressed. During the course of this project, we also began tracking our CLABSI rate for the entire patient population on the HM HSCT nursing unit along with the service-based rate noted above.
Slowing Progress in Cardiovascular Mortality Rates
Authors: Donald M. Lloyd-Jones
Journal: JAMA Cardiology (2016)

Stephen Sidney, MD, MPH; Charles P. Quesenberry Jr, PhD; Marc G. Jaffe, MD; Michael Sorel, MPH; Mai N. Nguyen-Huynh, MD; Lawrence H. Kushi, ScD; Alan S. Go, MD; Jamal S. Rana, MD, PhD
Abstract 039: Natural Killer T Cells Play Protective Roles in Cardiovirus-Induced Myocarditis by Inducing Anti-Viral and Regulatory Cytokines
Authors: Fumitaka Sato, Seiichi Omura, Nicholas E Martinez, Eiichiro Kawai, Sadie F Pearson, Viromi Fernando, Madan M Acharya, Ganta V Chaitanya, J. Steven Alexander, Maureen N Ajuebor, Masaru Taniguchi, Ikuo Tsunoda
Journal: Circulation Research (2013)

Picornavirus infections have been known as a leading cause of viral myocarditis in humans. Theiler’s murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus, the family Picornaviridae, and can cause myocarditis in susceptible mice. In viral myocarditis, viral replication in the heart and/or immune responses against virus as well as cardiac antigens (autoimmunity) can contribute to the pathogenesis. Natural killer T (NKT) cells can play a regulatory role in viral infections by producing anti-viral and anti-inflammatory cytokines; interferon (IFN)-γ can contribute to either viral clearance or tissue damage (immunopathology), while anti-inflammatory interleukin (IL)-10 has been suggested to regulate viral clearance or immunopathology. To determine the role of NKT cells in TMEV-induced myocarditis, we infected wild-type (WT) and NKT knockout (NKT KO, Jα18 KO) mice with TMEV. Myocarditis was monitored by echocardiography using the Vevo 770 system. During the acute (day 7) or chronic phase (day 60) of TMEV infection, cardiac pathology was evaluated by hematoxylin and eosin staining, and production of cytokines, including IFN-γ and IL-10, from spleen cells was measured by enzyme-linked immunosorbent assays. During the acute phase, the levels of left ventricular ejection fraction were significantly lower in NKT KO mice than in WT mice. Immunologically, NKT KO mice had lower levels of IFN-γ production than WT mice [IFN-γ (pg/ml): WT, 768 ± 533; NKT KO, 293 ± 190]. During the chronic phase, high intensity cardiac lesions were observed by echocardiography in NKT KO mice, but not in WT mice. Histologically, NKT KO mice developed moderate inflammation with basophilic degeneration and calcification in the heart, while WT mice had only mild inflammation in the heart. Immunologically, NKT KO mice had lower levels of IL-10 production compared with WT mice [IL-10 (pg/ml): WT, 1771 ± 381; NKT KO, 1199 ± 160]. These results suggest that NKT cells play a protective role in viral myocarditis by producing IFN-γ and IL-10, which contribute to viral clearance during the acute phase and the suppression of immunopathology during the chronic phase of disease, respectively.
Cutaneous alternariosis in a renal transplant recipient
Authors: Nawel Essabbah, Imen Gorsane, Monia Youssef, Rym Hadhri, Sabra Aloui, Mohamed Gorcii, Hichem Bel Hadj Ali, Zeineb Chemli, Hammouda Babba, Mezri El May, Jameleddine Zili, Abdelfatteh Zakhama, Habib Skhiri
Journal: Journal of the American Academy of Dermatology (2012)