tbuckley/cabot-search huggingface dataset:
Effectively treating CIPN.
Authors: Peter M Carney
Journal: Journal of Clinical Oncology (2015)

e20659 Background: Chemotherapy Induced Peripheral Neuropathy (CIPN) occurs in ~ 20-100% of cancer patients receiving chemotherapy based on the dose and type of cancer receiving treatment.1,2 Currently symptom modification remains our only treatment option,3 but has a less than 50% chance of helping patients reduce their pain by 50% and may cause many “adverse side effects.” Thus, no accepted standard protocol exists for treating CIPN.4 In 1943 the Nobel Laureate Edwin Schrodinger offered an alternative to the pharmacologic model by proposing that “living matter at the cellular level can be thought of in terms of quantum mechanics – pure physics and pure chemistry.”5 This suggests that signaling cells with electrical currents and electromagnetic energy fields can induce and amplify subatomic particle movement and activity to create healing within cells.6 A sophisticated electronic signaling technique (EST) produces profound anti-inflammatory effects.7 When combined with a local anesthetic it is called Combined Electrochemical Therapy (CET) and combats the various mechanisms involved in producing CIPN.8 A recent study has shown that CET more effectively treats neuropathy than does pharmacology.9 AIM: To confirm the efficacy and safety in using CET to treat CIPN. Methods: After initially evaluating 118 patients with CIPN, 95 patients (80%) received up to two CET treatments a week for as many as 56 treatments. The patients were analyzed in terms of their age sex, cancer diagnosis, co-existing causes of neuropathy, and whether they had finished their chemotherapy or still received treatment. Their highest VAS pain/discomfort scores as well as their highest Neuropathy Function Index (NFI) were compared to their last VAS and NFI score. Results: Sixty eight of these patients (72%) reduced their pain/discomfort by at least 30% and fifty two patients (55%) reduced their pain by 50% or more. The average patient improved their NFI by at least 45%. None had any “adverse side effects”. Twenty-five percent of the patients on CET continued to receive chemotherapy because of good symptom control. Conclusions: CET offers patients suffering from CIPN a safe and effective way to reduce their pain/discomfort, improve their functioning and to continue to receive chemotherapy.
Zika Vaccine Enters Clinical Trials
Authors: Jennifer Abbasi
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
P0430 : Delta like ligand 4 drives liver damage through regulating chemokines
Authors: Z. Shen, Y. Liu, J. Hu, O. Park, T. Feng, B. Dewidar, C. Xu, C. Yu, H. Li, H.G. Augustin, P. ten Dijke, B. Gao, M.P.A. Ebert, S. Dooley, Y. Li, H. Weng
Journal: Journal of Hepatology (2015)
First-in-human, phase I dose-escalation study of investigational drug MLN9708, a second-generation proteasome inhibitor, in advanced nonhematologic malignancies.
Authors: E. T. Rodler, J. R. Infante, L. L. Siu, D. C. Smith, D. Sullivan, G. Vlahovic, J. Gomez-Navarro, G. Liu, S. Blakemore, J. A. Thompson
Journal: Journal of Clinical Oncology (2010)

3071 Background: The investigational drug MLN9708 has shown antitumor efficacy in a wide range of tumor xenografts. It dissociates from the proteasome faster and has greater tissue penetration than bortezomib, which may enhance its antitumor activity. Both IV and oral formulations are in clinical development. Methods: Patients (pts) ≥18 y with refractory nonhematologic malignancies received IV MLN9708 on days 1, 4, 8, and 11 for up to 12 21-day cycles. Starting dose of 0.125 mg/m2 was doubled (1 pt/dose) until 1.0 mg/m2 based on occurrence of DLT in cycle 1, followed by a standard 3+3 dose-escalation scheme. Primary objectives were to assess safety, determine maximum tolerated dose (MTD) and recommend phase 2 dose. Secondary objectives were to assess pharmacokinetics (PK), whole blood 20S proteasome inhibition, and tumor response. Results: As of 12/8/09, 18 pts (7 male, median age 59 y) were enrolled, 1 each at 0.125, 0.25, and 0.5 mg/m2, and 6, 3, 3, and 3 at 1.0, 1.33, 1.76, and 2.34 mg/m2, respectively. Diagnoses were colon cancer 4, melanoma 3, renal cell carcinoma 3, leiomyosarcoma 2, pancreatic cancer 2, and 1 each with chondrosarcoma, rectal, lung, and prostate cancer. Pts up to dose level 1.76 mg/m2 were evaluable for safety: 1 DLT of grade (G) 3 rash was seen at 1.0 mg/m2. Most common adverse events (AEs) were fatigue (8), nausea (7), and pyrexia (6). G3/4 AEs included anemia (3) and thrombocytopenia (3). Seven pts experienced SAEs (2/9 were pretreatment events). While MTD has not yet been reached, DLT was seen in all 3 pts at 2.34 mg/m2 (2 reversible thrombocytopenia, 1 reversible renal failure) after data cut-off. Preliminary PK data indicate half-life of ∼7 days post day 11 dose. Systemic exposure (Cmax and AUC) appears dose-proportional. Proteasome inhibition in blood is greatest immediately post dosing, with substantial return to baseline by 2–4 hr as predicted from preclinical PK/PD modeling. Conclusions: MLN9708 appears generally well tolerated up to 1.76 mg/m2; assessment of 2.34 mg/m2 is ongoing. Pts with NSCLC, head/neck cancer, soft tissue sarcoma, and prostate cancer will enter the expanded cohort at MTD. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Merck, Millennium Millennium, Takeda Bayer, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Millennium, Novartis, Pfizer, Roche
P1-070: Bronchioloalveolar cell carcinoma and Adenocarcinoma with bronchioloalveolar cell feature: radiologic-pathologic correlation
Authors: Hyae Young Kim, Kun Young Lim, Soo-Hyun Lee, Geon Kook Lee, Jae Yoon Rho, Jong Mok Lee, Jae Ill Zo
Journal: Journal of Thoracic Oncology (2007)
Mechanisms by which obesity impacts upon asthma
Authors: Dale T Umetsu
Journal: Thorax (2016)

Asthma, an inflammatory disease of the airways, is a common condition, currently affecting about 9% of adults. Obesity is another disease with high prevalence in adults, and asthma that develops in obese individuals appears to be distinct from other forms of asthma, in being particularly severe and difficult to control even with oral corticosteroids. Moreover, recent studies suggest that obesity may have a causal relationship with asthma. In this review, we discuss possible obesity-driven metabolic and immunological pathways that might lead to asthma that is associated with obesity. Our understanding of the mechanisms that underlie this association will likely lead in the future to improved treatments for this significant unmet medical need.
One in five with bowel cancer diagnosed as emergency had previous “red flag” symptoms
Authors: Susan Mayor
Journal: BMJ (2016)

Nearly one in five patients who have bowel cancer diagnosed after presenting as emergencies have experienced at least one “red flag” cancer symptom in the year before diagnosis, a UK study has found.1

Researchers analysed clinical records of patients who had colon or rectal cancer diagnosed in England in 2005-06, looking for signs and symptoms reported to primary care in the five years before diagnosis and comparing symptom patterns in patients whose cancers were diagnosed on an emergency or …
Lateral-based Anterior Vaginal Wall Flap in the Treatment of Female Urethral Stricture: Efficacy and Safety
Authors: Jesús Romero-Maroto, Lidia Verdú-Verdú, Luis Gómez-Pérez, Carla Pérez-Tomás, Juan-José Pacheco-Bru, Ana López-López
Journal: European Urology (2016)
Microbes and Cancer
Authors: Amiran Dzutsev, Jonathan H. Badger, Ernesto Perez-Chanona, Soumen Roy, Rosalba Salcedo, Carolyne K. Smith, Giorgio Trinchieri
Journal: Annual Review of Immunology (2017)

Commensal microorganisms (the microbiota) live on all the surface barriers of our body and are particularly abundant and diverse in the distal gut. The microbiota and its larger host represent a metaorganism in which the cross talk between microbes and host cells is necessary for health, survival, and regulation of physiological functions locally, at the barrier level, and systemically. The ancestral molecular and cellular mechanisms stemming from the earliest interactions between prokaryotes and eukaryotes have evolved to mediate microbe-dependent host physiology and tissue homeostasis, including innate and adaptive resistance to infections and tissue repair. Mostly because of its effects on metabolism, cellular proliferation, inflammation, and immunity, the microbiota regulates cancer at the level of predisposing conditions, initiation, genetic instability, susceptibility to host immune response, progression, comorbidity, and response to therapy. Here, we review the mechanisms underlying the interaction of the microbiota with cancer and the evidence suggesting that the microbiota could be targeted to improve therapy while attenuating adverse reactions.
Platelet CD40L: a powerful leukocyte and endothelial cell activator in atherosclerosis
Authors: Dirk Lievens, Alma Zernecke, Roke Munnix, Linda Beckers, Erwin Wijnands, Randy J Noelle, Johan W Heemskerk, Christian Weber, Mat J Daemen, Esther Lutgens
Journal: Circulation (2007)
Characterisation of the faecal microbiota in Japanese patients with paediatric-onset primary sclerosing cholangitis
Authors: Kentaro Iwasawa, Wataru Suda, Tomoyuki Tsunoda, Manari Oikawa-Kawamoto, Shuichiro Umetsu, Ayano Inui, Tomoo Fujisawa, Hidetoshi Morita, Tsuyoshi Sogo, Masahira Hattori
Journal: Gut (2016)

Dear Sir,

Primary sclerosing cholangitis (PSC) is a liver disease often associated with IBD.1 Dysbiosis of the gut microbiota is implicated in PSC aetiology in adults,2–4 but less is known about paediatric-onset PSC.

We analysed the faecal microbiota of 27 Japanese patients with paediatric-onset PSC as well as 16 age-matched patients with UC and 23 healthy controls (HCs) (see online supplementary table S1) with pyrosequencing data of 16S rRNA gene V1-V2 region (accession #DRA004773). We assessed the influence of medications on the gut microbiota and found that salazosulfapyridine (SASP) treatment affected the microbiota structure with significant changes in the abundance of six major genera between the treated and untreated patients with PSC, perhaps due to its bactericidal property (see online supplementary figure S1). We thus report the analysis of 13 patients with PSC and 15 patients with UC and 23 HCs, all SASP untreated (see online supplementary table S2).

### Supplementary tables

[gutjnl-2016-312533supp_tables.pdf] 

### Supplementary figure

[gutjnl-2016-312533supp_figure.pdf] 

Clustering analysis of the 16S reads revealed that the microbiota in the PSC and HC groups had significantly high species richness compared with the UC group, and the species richness of PSC samples was lower than that of HCs. The PSC group also exhibited an intermediate trend in the Shannon's index between the UC and HC groups (figure 1A). The unweighted UniFrac metric revealed a significant difference in the overall microbiota structure among the three groups, in which the PSC samples tended to aggregate between the HC and UC samples (figure 1B, C). Collectively, the data suggested that the patients with …
Filaggrin failure - from ichthyosis vulgaris to atopic eczema and beyond
Authors: W.H.I. McLean
Journal: British Journal of Dermatology (2016)

The main proteinaceous component of the keratohyalin granules within the granular layer keratinocytes of the epidermis is the giant, repetitive polyprotein profilaggrin. When granular layer cells commit to terminal differentiation to form the flattened squames of the stratum corneum, profilaggrin is rapidly cleaved into multiple copies of the 37 kDa filaggrin monomer, which binds to and condenses the keratin cytoskeleton, thereby facilitating cellular compression. Within the stratum corneum, filaggrin is broken down to form natural moisturising factor, a pool of amino acids and derivatives thereof that exerts multiple effects. Filaggrin is therefore essential for normal stratum corneum biogenesis and physiology. In 2006, the McLean group identified the first loss-of-function mutations in the filaggrin gene (FLG) as the cause of the common monogenic genodermatosis ichthyosis vulgaris (IV). In parallel, they showed by multiple methods that these mutations, carried by up to 10% of various human populations are the major genetic predisposing factor for atopic dermatitis (eczema) and all of the associated allergic phenotypes that constitute the atopic diathesis. This paradigm-shifting work showed that skin barrier deficiency is a major early event in the pathophysiology of eczema and allergy.
P0800 : Effectiveness and safety of combination new regimens based on Sofosbuvir (SOFO) with Ribavirin (RBV), Daclatasvir (DAC) or Simeprevir (SIM) in difficult patients to treat infected with chronic hepatitis C (CHC)
Authors: B. Kutala, F. Mourri, N. Boyer, V. Sitruk, N. Giuily, C. Castelnau, P. Marcellin, T. Asselah
Journal: Journal of Hepatology (2015)
P0696 : Proteasome subunit alpha type-6 regulates the expression of proviral host genes in hepatitis C virus infection
Authors: R. Broering, M. Trippler, M. Lutterbeck, C.I. Real, D.A. Megger, T. Bracht, V. Schweinsberg, B. Sitek, M. Eisenacher, H.E. Meyer, H.A. Baba, F. Weber, A.-C. Hoffmann, G. Gerken, J.F. Schlaak
Journal: Journal of Hepatology (2015)
Does CTCAE toxicity symptom reporting by patients or clinicians predict clinical outcomes?
Authors: E. M. Basch, X. Jia, A. Barz, G. Heller, A. Culkin, M. Appawu, T. Barnett, F. Jason, M. G. Kris, D. Schrag
Journal: Journal of Clinical Oncology (2008)

6507 Background: During chemotherapy treatment and trials, it is standard for clinicians to report symptoms using the NCI Common Terminology Criteria for Adverse Events (CTCAE), which assigns grades via a 5-point scale. Patient-reporting has been proposed to supplement this information. It is not known if clinician or patient CTCAE grading predicts clinically meaningful outcomes. Methods: Lung cancer patients receiving chemotherapy and their paired clinicians reported 7 CTCAE symptoms and Karnofsky Performance Status (KPS) longitudinally as part of a prior feasibility study. To determine how patient and clinician-reported CTCAE symptoms compare in terms of predicting outcomes, a time-dependent Cox proportional hazards regression model was used to measure the association between reaching particular CTCAE grade thresholds (eg, grade 2 nausea) with risk of death or ER visits. Kendall's Tau correlation coefficients were calculated to measure concordance over time between each symptom and patient-reported EuroQoL EQ-5D health status index scores. Results: From June 2005, 163 patients were followed for an average of 12 months (range 1–28) with a mean of 11 visits and 67 (41%) deaths. Significant associations with survival and ER visits were seen for clinician-reported fatigue, nausea, pain, and KPS, but only for patient-reported pain, when either grade 2 or 3 was used as a threshold (Table). No associations were seen for vomiting, diarrhea, or constipation. Significant concordance with EQ-5D scores was seen for clinician and patient-reported fatigue, nausea, constipation, pain, and KPS. Higher relative Tau values for patient-reported symptoms demonstrated stronger associations with global health status vs. clinicians. Conclusions: Clinician symptom assessments better predict end-stage events, while patient self-assessments better indicate health status day-to-day. Care models should integrate patient and clinician reported data to inform clinical decisions and toxicity documentation in trials. Predictor Reporter (P=patient; C=clinician) Hazard Ratio for Death P-value Kendall's Tau with EQ-5D (all P<0.0001) Fatigue P 1.46 0.23 0.39 ′ C 3.13 0.0005 0.29 Nausea P 1.27 0.38 0.22 ′ C 1.98 0.01 0.11 KPS P 1.48 0.13 0.52 ′ C 5.14 <0.0001 0.29 Pain P 2.18 0.008 0.54 ′ C 1.86 0.02 0.37 No significant financial relationships to disclose.
Cardiomyocyte-specific overexpression of type 5 phosphodiesterase impairs postinfarction myocardial function and left ventricular remodeling
Authors: Peter Pokreisz, Marijke Pellens, An Van Den Bergh, Hilde Gillijns, Virginie Bito, Ilse Lenaers, Liesbeth Biesmans, Glenn Marsboom, Pieter Vermeersch, Jan D'hooge, Karin Sipido, Paul Herijgers, Luc Schoonjans, Kenneth D Bloch, Stefan Janssens
Journal: Circulation (2007)
Large‐scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis
Authors: Géraldine Dahlqvist, Farid Gaouar, Fabrice Carrat, Sofia Meurisse, Olivier Chazouillères, Raoul Poupon, Catherine Johanet, Christophe Corpechot
Journal: Hepatology (2016)

The prevalence, clinical characteristics, and outcomes of patients with antimitochondrial antibodies (AMAs), but no clinical evidence of primary biliary cholangitis (PBC), are largely unknown. A prospective study of AMA incidence was conducted through a nation-wide network of 63 French immunology laboratories. Clinical data from 720 of 1,318 AMA-positive patients identified in 1 year were collected. Patients were categorized as either newly diagnosed with PBC (n = 275), previously diagnosed with PBC (n = 216), or with nonestablished diagnosis of PBC (n = 229). The latter group was specifically evaluated. Follow-up data were collected for up to 7 years after detection of AMAs. Prevalence of AMA-positive patients without evidence of PBC was 16.1 per 100,000. These patients had the following characteristics: 78% female; median age 58 years; median AMA titer 1:160; extrahepatic autoimmune disorders 46%; normal serum alkaline phosphatases (ALP) 74%; ALP above 1.5 times the upper limit of normal 13%; and cirrhosis 6%. Compared to those newly diagnosed with PBC, the patients were slightly younger, had lower AMA titers, and lower sex-ratio imbalance. Among the patients with normal ALP and no evidence of cirrhosis, the 5-year incidence rate of PBC was 16%. Whereas no patients died from PBC, the 5-year survival rate was 75%, as compared to 90% in a control, standardized population matched for age and sex (P < 0.05). Conclusion: Nearly half of the newly detected AMAs in clinical practice does not lead to a diagnosis of PBC. PBC is unrecognized in 13% of those cases. Only 1 in 6 patients with AMAs and normal ALP will develop PBC after 5 years. The mortality of AMA-positive patients without PBC is increased irrespective of the risk of PBC development. (Hepatology 2017;65:152-163).
Phase Ib trial of cabazitaxel and tasquinimod in men with heavily pretreated metastatic castration resistant prostate cancer (mCRPC): The CATCH trial.
Authors: Andrew J. Armstrong, Patrick Healy, Russell Zelig Szmulewitz, Carolyn Winters, Michael Roger Harrison, Elia Martinez, Kelly Mundy, Susan Halabi, Daniel J. George
Journal: Journal of Clinical Oncology (2016)

190 Background: Cabazitaxel resistance develops within a few months of treatment initiation in most men with mCRPC in post-docetaxel, and thus combination therapy with other active agents may improve outcomes. Tasquinimod is an oral immunomodulatory agent with anti-angiogenic and anti-tumor in preclinical models of PC and clinical activity in phase II and III trials. Methods: We conducted a phase I dose escalation trial of cabazitaxel plus tasquinimod in men with mCRPC. Cabazitaxel was dosed at 25 mg/m2 every 3 weeks with low dose prednisone and PEG-filgrastim support, and tasquinimod dose levels included 0.25, 0.5, and 1.0 mg, using a 3 week within-patient dose escalation for dose levels 2 and 3, starting all patients at 0.25 mg once daily. The primary objective was to define the recommended phase II dose (RP2D) based on safety and dose limiting toxicity. Preliminary efficacy (PSA decline, PFS) and pharmacokinetic interactions were key secondary objectives. Results: We enrolled 25 men with mCRPC who had failed docetaxel across 3 dose levels. Median PSA at entry was 220 ng/dl. The RP2D was 0.5 mg tasquinimod based on excess DLTs (2 of 3 men) observed at dose level 3 (1.0 mg) including grade 3 sensory neuropathy and grade 3 atrial fibrillation). Dose level 2 was expanded to 14 men, where 3 DLTs were observed: grade 3 fatigue, grade 4 febrile neutropenia, and grade 3 liver function test abnormalities. The proportion of men with a &gt; 30% PSA decline was 63% (95% CI: 41%, 81%). The median composite PFS was 8.5 months (95% CI 4.2-16.4 months) based on 12 PFS events. The median number of cycles of cabazitaxel was 6 (range 1-13), with 6 men receiving &gt; 10 cycles. Best overall RECIST responses (CR+PR) were observed in 3 men (12%), stable disease in 12 (48%). No unexpected adverse events were observed and no pharmacokinetic interactions were observed. Conclusions: The RP2D was cabazitaxel 25 mg/m2 with prednisone and PEG-filgrastim every 3 weeks with tasquinimod 0.25 mg once daily for 3 weeks followed by 0.5 mg. Preliminary evidence of efficacy over cabazitaxel alone is based on observed PSA response and PFS data, and a substantial number of men were progression free beyond 10 cycles with good tolerability. Clinical trial information: NCT01513733.