tbuckley/cabot-search huggingface dataset:
Transarterial infusion chemotherapy alone versus transarterial chemoembolization for the treatment of hepatocellular carcinoma: Results of a multicenter randomized phase III trial
Authors: T. Okusaka, T. Sato, S. Hinotsu, Y. Shioyama, H. Kasugai, K. Tanaka, M. Kudo, T. Saisho, Y. Osaki, M. Sata, S. Fujiyama
Journal: Journal of Clinical Oncology (2007)

4643 Background: Transarterial chemoembolization (TAE) is widely used for patients (pts) with hepatocellular carcinoma (HCC) although evidence of a survival benefit remains controversial. A multicenter phase III trial was designed to compare the effects of TAE and transarterial infusion chemotherapy alone (TAI) on overall survival. Methods: Pts with newly diagnosed unresectable HCC were randomly assigned to either the TAE or the TAI group, stratified according to center and the serum alpha-fetoprotein level. Zinostatin stimalamer (SMANCS), up to a maximum of 6 mg, plus lipiodol emulsion with or without gelatin sponge was injected into the hepatic artery. Treatment was repeated when a follow-up computed tomography examination showed the appearance of new lesions in the liver or the regrowth of the treated tumors. Based on our previous phase II studies, reporting a 2-year survival rate of 80% in pts treated with TAE and of 60% in pts treated with TAI, 80 pts were needed in each group to achieve a level of statistical significance of 5% (2-sided) and a power of 80%. Results: From October 1999 to June 2003, 79 pts were assigned to the TAE group and 82 pts to the TAI group. The two groups were well balanced with regard to their baseline characteristics. The total number of treatment courses was 170 with a mean of 2.2 courses per patient (range, 1–9 courses) in the TAE group and 193 with a mean of 2.4 courses (range, 1–6 courses) in the TAI group. As of June 2005, 51 pts in the TAE group and 58 pts in the TAI group had died. The median overall survival time was 646 days in the TAE group and 679 days in the TAI group. No significant difference in survival was seen between the two groups (p=0.383). The mortality rate reduction for overall survival was 15.8% (95% CI, -24.1% to 42.9%) for the TAE relative to the TAI alone. Conclusions: This study suggests that treatment intensification as a result of embolization did not increase survival, compared with SMANCS transarterial chemotherapy alone, in pts with HCC. No significant financial relationships to disclose.
P85 Cognitive symptoms in chronic hepatitis C infection are associated with impaired cognitive test performance but are unrelated to peripheral markers of cellular immune activation
Authors: M Gess, D Forton
Journal: Gut (2010)

Introduction  Patients with hepatitis C virus (HCV) infection frequently complain of “brain fog” and impaired cognitive performance is well described in some patients. A direct virological effect of HCV on the CNS and a central effect of peripheral inflammation have both been hypothesised as mechanisms.  Aim  We aimed to determine whether cognitive symptoms are associated with markers of peripheral immune activation and objectively measured cognitive impairment.  Method  53 HCV patients with mild liver disease and 19 healthy controls, matched for age, sex, education and ethnicity, underwent computer-based cognitive testing (United BioSource, UK). The Medical Outcomes Survey Cognitive Function Scale (MOSCog) was used to assess cognitive symptoms. The Fatigue Impact Scale (FIS) and Beck Depression Inventory (BDI) were also employed. Serum neopterin was measured by ELISA, beta-2-microglobulin by nephelometric assay.  Results  19 (36%) HCV patients had MOSCog  Conclusion  In summary, important cognitive symptoms in over 1/3 of patients were associated with impaired performance on objective cognitive testing but were unrelated to markers of immune activation. It is unclear whether depression is a primary cause or occurs together with impaired cognition as a result of a direct effect of HCV on the brain.
How do I steer this thing? Using dendritic cell targeted vaccination to more effectively guide the antitumor immune response with combination immunotherapy
Authors: Stefanie N. Linch, William L. Redmond
Journal: Journal for ImmunoTherapy of Cancer (2016)

Mounting an immune response sufficient to eradicate a tumor is the goal of modern immunotherapy. Single agent therapies with checkpoint inhibitors or costimulatory molecule agonists are effective only for a small portion of all treated patients. Combined therapy, e.g., CTLA-4 and PD-1 checkpoint blockade, is a more effective treatment modality, but in preclinical studies OX40 agonism with CTLA-4 blockade using monoclonal antibodies (aOX40/aCTLA-4) failed to induce tumor regression of larger, more established tumors. We hypothesized that administration of a vaccine with a tumor-associated antigen targeted to the appropriate antigen presenting cell could make combined aOX40/aCTLA-4 therapy more effective. We administered an antibody-based vaccine targeting HER2 to the DEC-205 endocytic receptor on cross-presenting dendritic cells (anti-DEC-205/HER2; aDEC-205/HER2) and a potent adjuvant (poly (I:C)) to assist with maturation, along with aOX40/aCTLA-4 therapy. This therapy induced complete regression of established tumors and a pronounced infiltration of effector CD8 and CD4 T cells, with no effect on regulatory T cell infiltration compared to aOX40/aCTLA-4 alone. To be maximally effective, this therapy required expression of both OX40 and CTLA-4 on CD8 T cells. These data indicate that vaccination targeting cross-presenting dendritic cells with a tumor-associated antigen is a highly effective immunization strategy that can overcome some of the limitations of current systemic immunotherapeutic approaches that lack defined tumor-directed antigenic targets.
Clinical Features and Prognostic Factors in Adults with Bacterial Meningitis
Journal: New England Journal of Medicine (2005)

BACKGROUND: We conducted a nationwide study in the Netherlands to determine cl inical features and prognostic factors in adults with community acquired acute bacterial meningitis. METHODS: From October 1998 to April 2002, all Dutch patien ts with community acquired acute bacterial meningitis, confirmed by cerebrospin al fluid cultures, were prospectively evaluated. All patients underwent a neurol ogic examination on admission and at discharge, and outcomes were classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discha rge) or favorable (a score of 5). Predictors of an unfavorable outcome were iden tified through logis tic regression analysis. RESULTS: We evaluated 696 episod es of community acquired acute bacterial meningitis. The most common pathogens were Streptococcus pneumoniae (51 percent of pisodes) and Neisseria meningitidis (37 percent). The classic triad of fever, neck stiffness, and a change in menta l status was present in only 44 percent of episodes; however, 95 percent had at least two of the four symptoms of headache, fever, neck stiffness, and altered m ental status. On admission, 14 percent of patients were comatose and 33 percent had focal neurologic abnormalities. The overall mortality rate was 21 percent. T he mortality rate was higher among patients with pneumococcal meningitis than am ong those with meningococcal meningitis (30 percent vs. 7 percent, P 0.001). Th e outcome was unfavorable in 34 percent of episodes. Risk factors for an unfavor able outcome were advanced age, presence of otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on admission , tachycardia, a positive blood culture, an elevated erythrocyte sedimentation r ate, thrombocytopenia, and a low cerebrospinal fluid white cell count. In adult s presenting with community acquired acute bacterial meningitis, the sensitivit y of the classic triad of fever, neck stiffness, and altered mental status is lo w, but almost all present with at least two of the four symptoms of headache, fe ver, neck stiffness, and altered mental status. The mortality associated with ba cterial meningitis remains high, and the strongest risk factors for an unfavorab le outcome are those that are indicative of systemic compromise, a low level of consciousness, and infection with S. pneumoniae.
Chorioamnionitis complicated by an intrauterine device.
Authors: Jewett Jf
Journal: New England Journal of Medicine (1973)

A case report of chorioanmionitis complicated by an IUD and resulting in death is presented.  A 27-year-old para 2 conceived during the amenorrhea of lactation despite an IUD which was inserted 6 weeks postpartum.  The identifying filament was not seen when the patient was examined in the first trimester but the pregnancy was uneventful until spontaneous rupture of the membranes at 22 weeks.  The patient was sent home after amniotic-fluid leakage was confirmed.  She returned within 24 hours with an elevated temperature.  Cultures revealed Escherichia coli and the syndrome of gram-negative endotoxin became evident.  A macerated fetus and the placenta were delivered but not the IUD.  The patient was treated with oxygen and chloramphenicol.  Surgical intervention was instituted 26 hours after admission and 20 hours postpartum.  Panhysterectomy was performed.  Homeostasis was reestablished but the patient remained cyanotic and hypoxic.  Death from respiratory failure occurred on the 12th day.  The author stated that simple adherence to established obstetric principles could have prevented this death especially the serious error to send this patient home after amniotic-fluid leakage was confirmed.  Other possible errors are discussed.
Targeted Therapy for Metastatic Urothelial Cancer: A Work in Progress
Authors: Elizabeth R. Plimack, Daniel M. Geynisman
Journal: Journal of Clinical Oncology (2016)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 64-year-old man presented to the clinic to discuss treatment options for progressive metastatic urothelial carcinoma (UC). At age 57 years, he underwent cystoprostatectomy for bacillus Calmette-Guérin-refractory, high-grade noninvasive UC. He was well until age 61 years, when he developed a left upper-tract UC. He underwent left nephroureterectomy, revealing locally advanced high-grade UC invading the renal parenchyma (pT3). Postoperatively, his renal function precluded adjuvant cisplatin-based chemotherapy. He enrolled onto a clinical trial of autologous cellular immunotherapy targeting human epidermal growth factor receptor 2, for which he was eligible on the basis of human epidermal growth factor receptor 2 positivity (≥ 1+ by immunohistochemistry) in his nephrectomy tumor specimen. He was randomly assigned to observation. Two years later, he developed a left pelvic mass. Biopsy confirmed metastatic high-grade UC. He was briefly treated with gemcitabine and carboplatin, but this was discontinued as a result of rapid symptomatic and radiographic progression at 8 weeks. He underwent palliative radiation to the left pelvic mass to relieve symptoms of pain and leg edema and subsequently elected to enroll onto a clinical trial of a programmed death 1 inhibitor. Concurrently, his previously obtained pelvic mass biopsy sample was sent for panel-based genomic profiling. He now returns for his first restaging evaluation. Imaging shows marked progression on study with new metastases to the liver as well as progressive edema and pain in the left leg, limiting ambulation. Review of his now-available genomic testing results reveals alterations in HRAS (G12D) and ATR (S296, Q257). He elected to enroll onto a single-arm, open-label trial of a farnesyl transferase inhibitor for patients with HRAS mutations.
Prospective Analysis of Oncogenic Driver Mutations and Environmental Factors: Japan Molecular Epidemiology for Lung Cancer Study
Authors: Tomoya Kawaguchi, Yasuhiro Koh, Masahiko Ando, Norimasa Ito, Sadanori Takeo, Hirofumi Adachi, Tsutomu Tagawa, Seiichi Kakegawa, Motohiro Yamashita, Kazuhiko Kataoka, Yukito Ichinose, Yukiyasu Takeuchi, Masakuni Serizawa, Akihiro Tamiya, Shigeki Shimizu, Naoki Yoshimoto, Akihito Kubo, Shun-ichi Isa, Hideo Saka, Akihide Matsumura
Journal: Journal of Clinical Oncology (2016)

Oncogenic driver mutations are critical for lung cancer development and serve as therapeutic targets. However, their associations with environmental factors are not fully understood. We aimed to elucidate the relationship between tumor developmental biology and exposure to environmental factors.This was a prospective, multicenter, molecular epidemiology study. Eligible patients were those with newly diagnosed stages I to IIIB non-small-cell lung cancer (NSCLC) who underwent surgery. The tumors were examined for somatic mutations in 72 cancer-associated genes by targeted deep sequencing, estrogen receptor β (ERβ) expression using immunohistochemical staining, and infection with any of 37 types of human papillomavirus (HPV) using a polymerase chain reaction-based microarray system. Detailed information on patient demographics and environmental factors was obtained from a comprehensive questionnaire.From July 2012 to December 2013, 957 patients were enrolled, and molecular analyses were performed on 876 samples (from 441 ever- and 435 never-smokers). Oncogenic driver mutations in P53 and KRAS increased proportionally with smoking status, whereas mutations in EGFR and SMAD4 decreased. KRAS mutations in smokers and SMAD4 mutations were observed more frequently in proportion to body mass index. TP53 and NFE2L2 mutations were observed more frequently in advanced NSCLC stages. As for never-smokers, no environmental factors were significantly associated with mutational changes. EGFR mutations and TP53 mutations were observed more frequently in women and in men, respectively. Mutations in these two genes were also potentially associated with ERβ expression. Only three patients (0.3%) were HPV positive.The mutational spectrum is associated with smoking, body mass index, and other environmental factors, as well as with ERβ expression. Little association was observed between HPV and NSCLC.
Overcoming multidrug resistance in Dox-resistant neuroblastoma cell lines via treatment with HPMA copolymer conjugates containing anthracyclines and P-gp inhibitors
Authors: Eva Koziolová, Olga Janoušková, Lucie Cuchalová, Zuzana Hvězdová, Jan Hraběta, Tomáš Eckschlager, Ladislav Sivák, Karel Ulbrich, Tomáš Etrych, Vladimír Šubr
Journal: Journal of Controlled Release (2016)
Modification of the Sengstaken–Blakemore Balloon Tube
Authors: H. Worth Boyce
Journal: New England Journal of Medicine (1962)

THE Sengstaken–Blakemore1 balloon tube has been modified by the attachment of a standard plastic nasogastric tube. The tip of the plastic tube is secured at a point just above the proximal end of the esophageal balloon by passage of a piece of No. 0000 blacksilk suture through the wall of the nasogastric tube, and a tie is made around the circumference of the rubber tube (Fig. 1). Four or five similar attachments are made between the tubes proximally at 7.6cm. intervals, as shown in Figure 2. The addition of this plastic tube has not caused any difficulty to date with either . . .
Supervoltage X-Ray Therapy: A Report for the Years 1937–1942 on The Mozelle Sassoon Supervoltage X-Ray Therapy Department, St. Bartholomew's Hospital. By Ralph Phillips, with the technical assistance of G. S. Innes. With a Foreword by The Rt. Hon. The Lord Horder. London: H. K. Lewis and Company, Ltd., 1944, vii-142 pages. Price 16s
Authors: Edith H. Quimby
Journal: Cancer Research (1945)
Early Response to Everolimus Therapy Detected on 68Ga-DOTATATE PET/CT in a Patient With Pancreatic Neuroendocrine Tumor
Authors: Elgin Ozkan, Cigdem Soydal, Sibel Ucak Semirgin, Oktay Yapici, Aysegul Atmaca, Guzin Demirag
Journal: Clinical Nuclear Medicine (2016)

Everolimus is a mammalian target of rapamycin inhibitor that has been recently approved for the treatment of patients with advanced progressive pancreatic neuroendocrine tumor. Here, we present a case in which an early therapy response to everolimus was effectively demonstrated by Ga-DOTATATE PET/CT.
Treatment of AL Amyloidosis with 4′-Iodo-4′-Deoxydoxorubicin: An Update
Authors: Giampaolo Merlini, Ernesto Anesi, Pietro Garini, Vittorio Perfetti, Laura Obici, Edoardo Ascari, Maria J. Lechuga, Giuseppe Capri, Luca Gianni
Journal: Blood (1999)
Fine-Needle Aspiration Biopsy of Palpable Breast Masses: Patterns of Clinical Use and Patient Experience
Authors: Amy Ly, Jill C. Ono, Kevin S. Hughes, Martha B. Pitman, Ronald Balassanian
Journal: Journal of the National Comprehensive Cancer Network (2016)

Timeliness is an important and recognized measure of health care quality. Multiple health organizations worldwide have published timeliness targets for breast cancer care. We performed the first comparison of patient wait times and utilization patterns for palpable breast mass diagnosis and treatment with regard to biopsy method.Palpable breast masses in women biopsied via a fine-needle aspiration (FNA) or core biopsy at 2 affiliated academic medical centers in 2009 were analyzed if subsequently treated with excision or neoadjuvant therapy. Patient demographics, mass size and radiologic features, pathology diagnoses, and wait times to diagnosis and treatment were recorded.Patients diagnosed by FNA biopsy received their biopsy diagnosis more than 8 days sooner than those diagnosed by core biopsy. Most FNA biopsies occurred the same day the patient clinically presented. Time to treatment did not differ significantly between groups. Both biopsy methods demonstrated comparable diagnostic accuracy. Breast masses diagnosed by FNA biopsy had Breast Imaging Reporting and Data System (BI-RADS) scores ranging from 1 through 5, whereas nearly all core biopsy cases had a BI-RADS score of 4 or greater. All patient groups were demographically comparable and presented with similar breast mass sizes.Wait times for breast biopsies were significantly shorter for patients diagnosed by FNA compared with core biopsy. FNA biopsy was often used to evaluate breast masses of low clinical suspicion. In light of health care goals for practice improvement and cost containment, breast FNA biopsy may be an underused resource.
Radiation-induced esophagitis: A double-blind randomized clinical trial of aluminum hydroxide plus magnesium hydroxide plus oxetacaine suspension versus aluminum hydroxide plus magnesium hydroxide suspension
Authors: F. Bruns, D. Riesenbeck, R. Muecke, M. Klasser, N. Willich
Journal: Journal of Clinical Oncology (2007)

9100 Background: To assess whether oral administered oxetacaine-containing suspension is effective in treating acute radiation- induced esophagitis in cancer patients. Methods: A double-blind, prospective-randomized clinical trial was conducted across 20 radiotherapy institutions in Germany. Patients [pts.] with head and neck or thoracic cancer without dysphagia/odynophagia received definitive or postoperative radiotherapy [RT] with or without chemotherapy including at least 5 cm of the esophagus in the high dose volume. Pts. were randomized to receive oral aluminum hydroxide plus magnesium hydroxide plus oxetacaine (Tepilta [T]) suspension or aluminum hydroxide plus magnesium hydroxide suspension without oxetacaine (Magaldrat [M]) as first-line treatment for acute radiation-induced esophagitis. Primary endpoint was the interval between begin of RT and failure of first-line treatment of esophagitis defined as need for additional systemic analgesics. Data on pts.’ symptoms were collected during and for at least 2 weeks after treatment. Results: A total of 158 pts. were randomized, of whom 103 had take at least one dose of the study medication for acute esophagitis = grade 2 (CTC). Of the 105 pts., 51 were randomized to receive T and 52 M. The cumulative incidence of acute esophagitis = grade 2 (CTC) was 25% for the T and 22% for the M arm. Kaplan-Meier analysis showed a statistically significant difference between the two groups regarding the need for systemic analgesics under consideration of the intake time in favor of T (p = 0.032). No statistically significant difference was found between the two groups regarding the secondary endpoints need respective delay of additional parenteral nutrition (p = 0.28 respective p = 0.12), and pts.`s and investigator`s estimation of global effectivity of the study medication (0.08 and 0.12). Conclusions: This trial demonstrated a statistically significant delay of the intake time for systemic analgesics in pts. randomized to receive oral aluminum hydroxide plus magnesium hydroxide plus oxetacaine suspension. No significant financial relationships to disclose.
Gait Speed and Operative Mortality in Older Adults Following Cardiac Surgery
Authors: Jonathan Afilalo, Sunghee Kim, Sean O’Brien, J. Matthew Brennan, Fred H. Edwards, Michael J. Mack, James B. McClurken, Joseph C. Cleveland, Peter K. Smith, David M. Shahian, Karen P. Alexander
Journal: JAMA Cardiology (2016)

Prediction of operative risk is a critical step in decision making for cardiac surgery. Existing risk models may be improved by integrating a measure of frailty, such as 5-m gait speed, to better capture the heterogeneity of the older adult population.To determine the association of 5-m gait speed with operative mortality and morbidity in older adults undergoing cardiac surgery.A prospective cohort study was conducted from July 1, 2011, to March 31, 2014, at 109 centers participating in the Society of Thoracic Surgeons Adult Cardiac Surgery Database. The 5-m gait speed test was performed in 15 171 patients aged 60 years or older undergoing coronary artery bypass graft, aortic valve surgery, mitral valve surgery, or combined procedures.All-cause mortality during the first 30 days after surgery; secondarily, a composite outcome of mortality or major morbidity during the index hospitalization.Among the cohort of 15 171 patients undergoing cardiac surgery, the median age was 71 years and 4622 were female (30.5%). Compared with patients in the fastest gait speed tertile (>1.00 m/s), operative mortality was increased for those in the middle tertile (0.83-1.00 m/s; odds ratio [OR], 1.77; 95% CI, 1.34-2.34) and slowest tertile (<0.83 m/s; OR, 3.16; 95% CI, 2.31-4.33). After adjusting for the Society of Thoracic Surgeons predicted risk of mortality and the surgical procedure, gait speed remained independently predictive of operative mortality (OR, 1.11 per 0.1-m/s decrease in gait speed; 95% CI, 1.07-1.16). Gait speed was also predictive of the composite outcome of mortality or major morbidity (OR, 1.03 per 0.1-m/s decrease in gait speed; 95% CI, 1.00-1.05). Addition of gait speed to the Society of Thoracic Surgeons predicted risk resulted in a C statistic change of 0.005 and integrated discrimination improvement of 0.003.Gait speed is an independent predictor of adverse outcomes after cardiac surgery, with each 0.1-m/s decrease conferring an 11% relative increase in mortality. Gait speed can be used to refine estimates of operative risk, to support decision-making and, since incremental value is modest when used as a sole criterion for frailty, to screen older adults who could benefit from further assessment.