tbuckley/cabot-search huggingface dataset:
Популяційні зміни порожнинної мікробіоти товстої кишки хворих на хронічний вірусний гепатит С
Authors: D.V. Rotar, L.I. Sydorchuk, A.S. Sydorchuk, S.E. Dejneka, I.I. Sydorchuk
Journal: GASTROENTEROLOGY (2017)

Актуальність. Гепатит С залишається однією з провідних проблем внутрішньолікарняних інфекцій, пов’язаних із гемотрансфузіями, введенням препаратів крові, медичними інвазивними маніпуляціями з діагностичною та лікувальною метою. Мета дослідження: установити популяційний рівень таксонів мікробіоти порожнини товстої кишки хворих на хронічний гепатит С. Матеріали та методи. Мікробіологічному дослідженню підлягали 72 зразки вмісту порожнини товстої кишки хворих на хронічний гепатит С, із них жінок було 44, чоловіків — 28, вік хворих становив від 21 до 53 років (у середньому — 37,5 ± 1,7 року). Результати. На основі проведених досліджень установлено, що популяційний рівень бактерій роду Bifidobacterium у порожнині товстої кишки хворих на хронічний гепатит С знижується на 41,28 %, Lactobacillus spp. — на 41,15 %, коефіцієнт кількісного домінування зменшується у 2,07 і 2,22 раза, коефіцієнт значущості — у 3,25 та 3,36 раза відповідно, що сприяє підвищенню популяційного рівня, коефіцієнта кількісного домінування і значущості Bacteroides spp. на 65,01 та 24,94 % відповідно, підвищується на 52,21 % кількість бактерій Escherichia spp., на 26,48 % — Enterococcus spp., на 57,43 % — Peptostreptococcus spp., у 2,03 раза — бактерій роду Clostridium. Результати проведеного дослідження дають можливість практичному лікарю ефективно проводити етіотропну терапію та корекцію змін біотопу пробіотичними засобами з урахуванням кількісних змін даного мікробіоценозу. Висновки. У порожнині товстої кишки хворих на хронічний гепатит С формується виражений дефіцит автохтонних облігатних Bifidobacterium spp. на 41,28 %, Lactobacillus spp. — на 42,15 %, зростає концентрація в біотопі Bacteroides spp. на 65,01 %, Peptostreptococcus spp. — на 57,43 %, Clostridium spp. — у 2,03 раза, а також бактерій роду Escherichia — на 52,21 %, Enterococcus spp. — на 26,48 %. За змінами популяційного рівня головної, додаткової і випадкової мікробіоти порожнини товстої кишки в більшості хворих на хронічний гепатит С діагностований дисбіоз/дисбактеріоз ІІ і ІІІ ступенів (80,56 %).
A single-center study of cancer and chemotherapy-induced kidney disease.
Authors: Abu-Sayeef Mirza, Sarah Mushtaq, Revati Reddy, Mina Mousa, Chandrashekar Bohra, Kullatham Kongpakpaisarn, Sean Verma, Rahul Suresh Mhaskar, Michael Vishal Jaglal, Claude Bassil
Journal: Journal of Clinical Oncology (2017)

e13062 Background: It is clinically understood that chronic kidney disease (CKD) and cancer are interrelated. Yet, few studies measure how renal outcomes vary according to common malignancies and common therapeutic agents. We report the incidence and the nature of CKD among cancer patients from a single institution. Methods: A retrospective chart review of cancer patients managed in the onconephrology clinic at the Moffitt Cancer Center from 05/01/2015 to 07/31/2016 was conducted. Patients with acute or chronic kidney disease secondary to a malignancy or side effect of chemotherapy were included in this study. Renal function outcomes were recorded at three-month follow-up intervals from the 15-month duration. Results: Out of the total 88 patients with median age of 68 years, 63 patients were diagnosed with chronic kidney disease, whereas the remaining had acute kidney injury. Kidney cancer and multiple myeloma represented the largest proportion with 12 patients each. Patients with kidney cancer had a mean creatinine of (2.35, 1.74) mg/dl compared to patients without kidney cancer with creatinine (1.97, 1.07) mg/dl. Abdominal cancers had the highest proportion of chronic kidney disease (84.21%) whereas 81.48% of patients with genitourinary cancers had chronic kidney disease. Patients prescribed tyrosine kinase inhibitors had a lower average estimated glomerular filtration rate (28.37, 9.86) mL/min/1.73 m 2 compared to other chemotherapeutic agents, though this was a weakly significant relationship (p-value = 0.07). Similar renal outcomes according to malignancy and chemotherapy are reported. Conclusions: This group of patients demonstrated the frequency of chronic kidney disease differs depending on the type of malignancy or chemotherapy. A multidisciplinary approach involving oncologists and nephrologists should be adopted to prevent further renal damage from cancer and its therapies.
The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics
Authors: Kelly S. Swanson, Glenn R. Gibson, Robert Hutkins, Raylene A. Reimer, Gregor Reid, Kristin Verbeke, Karen P. Scott, Hannah D. Holscher, Meghan B. Azad, Nathalie M. Delzenne, Mary Ellen Sanders
Journal: Nature Reviews Gastroenterology & Hepatology (2020)

Abstract In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept.
Echographie de contraste avec Sonovue: apport dans la caractérisation des lésions hépatiques
Authors: H Trillaud, JF Blanc, C Laurent, JB Galtier, M Bouzgarrou, C Balabaud
Journal: Endoscopy (2005)

échographie, TDM et IRM. Le but de cette étude a été d'évaluer chez 117 patients consécutifs l'apport de l'échographie de contraste dans la caractérisation de tumeurs hépatiques en comparaison avec le TDM et/ou l'IRM.
Comparison of CEF (C: cyclophosphamide, E: epirubicin, and 5FU) and EC (E: epirubicin and C: cyclophosphamide) therapy in neoadjuvant setting for axillary lymph node metastasis-positive breast cancer.
Authors: Yuko Kawai, Takashi Ishikawa, Kimito Yamada, Hiroshi Kaise, Eiichi Sato, Mari Hosonaga, Saeko Teraoka
Journal: Journal of Clinical Oncology (2016)

e12520 Background: It is not clear which anthracycline regimen for breast cancer is most effective in the neoadjuvant chemotherapy. We compared CEF therapy with EC therapy in neoadjuvant setting for axillary lymph nodes metastasis-positive breast cancer in our hospital in order to examine which anthracycline regimen is more effective. Methods: We treated 221 cases (cT1-4 N1-3 M0) of breast cancers, performed operation after neoadjuvant chemotherapy (anthracycline and taxanes) in May 2003 to July 2014. The average observation period was 5.5 years. We separated 2 groups, CEF and EC. CEF group were patients performed CEF therapy (C: 500mg/m², E: 100mg/m², 5FU: 500mg/m² every 3 weeks intravenous drip) followed by taxanes. EC group were patients performed EC therapy (E: epirubicin 90mg/m², C: cyclophosphamide 600mg/m² every 3 weeks intravenous drip) followed by taxanes. Some patients received zoledronic acid or denosumab in clinical trials. We examined the percentage of pCR (pathological complete response), the death rate and the recurrence rate in each group. Results: CEF group were 57 cases, the median age was 51, the percentage of patients with hormone-receptor (HR) positive & HER2 negative was 59.6%, HR positive & HER2 positive 12.3%, HR negative & HER2 positive 12.3%, and triple negative 15.8%. The pCR rate was 19.3%. The death rate was 12.3%. The recurrence rate was 15.6%. The cases received zoledronic acid were 11. EF group were 164 cases, the median age was 52, the percentage of patients with HR positive & HER2 negative was 47.0%, HR positive & HER2 positive 25.6%, HR negative & HER2 positive 15.2%, and triple negative 13.4%. The pCR rate was 25.0%. The death rate was 9.1%. The recurrence rate was 17.1%. The case received zoledronic acid was 1. The cases received denosumab were 3.There were no discontinuations of treatment by side effect of anthracycline and other diseases. Conclusions: Inspite of a bias in the number of cases in the CEF group and the EC group, there was no significant difference in the death rate and recurrence rate.
Clonality and X-inactivation patterns in hematopoietic cell populations detected by the highly informative M27 beta DNA probe [see comments]
Authors: MF Fey, S Liechti-Gallati, A von Rohr, B Borisch, L Theilkas, V Schneider, M Oestreicher, S Nagel, A Ziemiecki, A Tobler
Journal: Blood (1994)
The effect of age on symptom reporting on the adult and child post concussion symptom scale in youth ice hockey players
Authors: Amanda M Black, Kathryn J Schneider, Luz Palacios-Derflingher, Willem H Meeuwisse, Carolyn A Emery
Journal: British Journal of Sports Medicine (2017)

Objective To determine symptom reporting differences for children completing the adult and child version of the Post-Concussion Symptom Scale (PCSS) on the Sport Concussion Assessment Tool 3 (SCAT3). Design Cross-Sectional study. Setting Community ice hockey teams, Alberta, Canada. Participants Youth hockey players (n=891; 91.58% male, 10–14 years) who completed the PCSS on the Adult and Child version of the SCAT3 during a preseason baseline assessment. Assessment of risk factors Adult versus child PCSS stratified by categorical age (10–12, 13–14). Outcome measures Total number of symptoms, symptoms reported, and proportion equally reporting symptoms (0, ≥1) on both PCSS scales. Main results Participants reported a median of 2 symptoms [Interquartile Range (IQR):0–21] on the adult scale (/22) and 5 (IQR:0-20) on the child scale (/20). There was no evidence of a difference in the proportion of participants reporting symptoms (0, ≥1) on both scales between age groups 10–12 (525/729, 72.02%) and 13–14 (121/160, 75.63%) (difference: −3.61% (95% confidence interval (−11.40%, 4.18%)). The most frequent symptoms reported on the adult PCSS by participants with no symptoms on the child PCSS were nervousness (11.27%) and neck pain (10.56%). Participants with no symptoms on the adult PCSS most commonly reported being easily distracted (45.29%) and forgetful (39.49%) on the Child PCSS. Conclusions A greater number of symptoms were endorsed for all 10-14 year old subjects when using the Child SCAT3 PCSS. Neck pain was a commonly reported symptom for all age groups on the Adult SCAT3 PCSS, but this symptom is absent from the Child SCAT3. Competing interests None.
Indicators of clinical response to abiraterone acetate (AA) in men with metastatic castration-resistant-prostate-cancer (mCRPC).
Authors: Martin Boegemann, Phillip Mikah, Okyaz Eminaga, Edwin Herrmann, Philipp Marius Papavassilis, Axel Semjonow, Laura-Maria Krabbe
Journal: Journal of Clinical Oncology (2014)

e16066 Background: AA prolongs survival in men with mCRPC in the pre- and postchemotherapy (CTX) setting. Surrogate biomarkers of clinical response (CR) are scarcely established. PSA- and LDH-changess on its own, especially in the beginning of therapy, are often misleading and circulating tumor cells (CTCs) are not routinely available. This retrospective study was conducted to identify and analyze possible indicators of response to AA in men with mCRPC. Methods: All men with mCRPC receiving AA between December 2009 and June 2012 at the University Hospital of Muenster were included and analyzed. PSA response rate (RR) was monitored according to PCWG2 criteria and assessed 12 weeks after start of treatment. Potential indicators of CR were analyzed using uni- and multivariate (UV/MV) logistic regression models. Initial increase of ALP after the beginning of AA treatment with a subsequent clinically significant decline below baseline was defined as ALP-bouncing. Results: 43 patients were evaluable for analysis: 36 men were CTX naïve, 7 preteated with CTX. The median PSA RR was 44%. In UV ALP-bouncing, normalization of LDH and PSA-decline of ≥50% during the first 12 weeks of AA therapy as well as initially normal LDH were all significantly associated with CR. In MV LDH normalization and coincidental AP-bouncing were associated with better CR (risk for no response to AA: Hazard Ratio (HR) of 0.037 (0.004-0.391), p=0.005). In the cases of initially increased LDH that remained elevated under AA, AP-bouncing was associated with CR as well (risk for no response to AA HR: 0.048 (0.004-0.515), p=0.010). For patients with no PSA-decline of ≥50% AP-bouncing did not indicate CR (odds ratio (OR) 0.7 (0.078-6.223), p=0.749). Initially normal, continuously normal or normalization of LDH were associated with a better response than rising LDH (risk for no CR to AA: OR 0.048 (0.003 – 0.712, p=0.0274). Conclusions: A normal LDH prior to AA treatment or LDH normalization during treatment, PSA-decline of ≥50% and bouncing of ALP during the first 12 weeks of therapy are strongly associated with better CR. Continuously rising ALP after 12 weeks of therapy indicated no further clinical benefit when therapy was continued.
Differential effects on gene transcription and hematopoietic differentiation correlate with GATA2 mutant disease phenotypes
Authors: C-E Chong, P Venugopal, P H Stokes, Y K Lee, P J Brautigan, D T O Yeung, M Babic, G A Engler, S W Lane, M Klingler-Hoffmann, J M Matthews, R J D'Andrea, A L Brown, C N Hahn, H S Scott
Journal: Leukemia (2017)

Heterozygous GATA2 mutations underlie an array of complex hematopoietic and lymphatic diseases. Analysis of the literature reporting three recurrent GATA2 germline (g) mutations (gT354M, gR396Q and gR398W) revealed different phenotype tendencies. Although all three mutants differentially predispose to myeloid malignancies, there was no difference in leukemia-free survival for GATA2 patients. Despite intense interest, the molecular pathogenesis of GATA2 mutation is poorly understood. We functionally characterized a GATA2 mutant allelic series representing major disease phenotypes caused by germline and somatic (s) mutations in zinc finger 2 (ZF2). All GATA2 mutants, except for sL359V, displayed reduced DNA-binding affinity and transactivation compared with wild type (WT), which could be attributed to mutations of arginines critical for DNA binding or amino acids required for ZF2 domain structural integrity. Two GATA2 mutants (gT354M and gC373R) bound the key hematopoietic differentiation factor PU.1 more strongly than WT potentially perturbing differentiation via sequestration of PU.1. Unlike WT, all mutants failed to suppress colony formation and some mutants skewed cell fate to granulocytes, consistent with the monocytopenia phenotype seen in GATA2-related immunodeficiency disorders. These findings implicate perturbations of GATA2 function shaping the course of development of myeloid malignancy subtypes and strengthen complete or nearly complete haploinsufficiency for predisposition to lymphedema.
Results from the biomarker-driven basket trial of RO5126766 (CH5127566), a potent RAF/MEK inhibitor, in RAS- or RAF-mutated malignancies including multiple myeloma.
Authors: Maxime Chenard-Poirier, Martin Kaiser, Kevin Boyd, Priya Sriskandarajah, Anastasia Constantinidou, Samuel John Harris, Sonia Serrano Fandos, Alison Ryan, Karolina Witt, Joanna C Dawes, Mona Parmar, Alison Joanne Turner, Holly Tovey, Emma Hall, Raquel Perez Lopez, Nina Tunariu, Juanita Suzanne Lopez, Johann S. De Bono, Udai Banerji
Journal: Journal of Clinical Oncology (2017)

2506 Background: RO5126766 is a potent RAF and MEK inhibitor with activity in xenografts models of RAS and RAF-mutated cancers. We present data from the RAS/RAF-mutated advanced solid tumor cohort and the initial results for the multiple myeloma (MM) cohort. Methods: Patients with KRAS, NRAS or BRAF-mutant tumours were treated with RO5127566 using a novel schedule:4mg twice weekly in 4-week cycles. For MM patients, it was given 3 weeks out of 4 and co-administration of weekly dexamethasone was authorised. Response assessment was completed using RECIST 1.1 criteria for solid tumours and the International Myeloma Working Group (IMWG) criteria were used for MM. Results: A total of 20 patients with solid tumours (10 NSCLC, 5 gynaecological cancers and 5 miscellaneous cancers) and 1 MM patients were evaluable. Among the 10 KRAS-mutant NSCLC patients, tumour regression was seen in 6/10 (60 %), of which 3/10 (30 %) were partial responses. Two of these patients had maintained response for over 1 year and one patient is still on study after 30 cycles. Of the gynaecological cancers, 3/5 patients (60%) achieved a partial response ( KRAS-mutant endometrial and ovarian cancer and BRAF-mutant ovarian). Of these patients, 1 of the KRAS mutants had received 2 previous lines of MEK inhibitors and the BRAF mutant had previously received a BRAF inhibitor. In the miscellaneous group, 4 patients with colorectal cancer (2 BRAF and 2 NRAS) and 1 patient with NRAS-mutant melanoma were treated and none responded. Two patients with MM have been treated so far (1 KRAS, 1 KRAS+NRAS). The one evaluable patient has had an IMWG partial response (PR) after 1 cycle (FLC-λ from 324 mg/L to 161mg/L, ratio 0.03 to 0.08) without concomittant dexamethasone. This patient was previously treated with an immunomodulatory drug, a proteasome inhibitor and two ASCTs. Conclusions: RO5126766 has shown exciting preliminary activity across a wide range of RAS- and RAF-mutated malignancies, with significant response rates in lung and gynaecological cancers. To our knowledge, the PR seen in our MM patient represents one of the first responses to a single-agent RAF/MEK inhibitor in multiple myeloma in a trial context. Clinical trial information: NCT02407509.
Viral Hepatitis: Epidemiology and Diagnosis
Journal: Hepatology (2013)

trypsin disease, Wilson's disease, and hemochromatosis were negative.Abdo ultrasound demonstrated diffuse, extensive steatosis in all the patients and nodules consistent with hepatocellular carcinoma (HCC) in two patients.RESULTS:BMI for all patients was over 30, and alcohol consumption was not significant.In all liver biopsies diffuse, macrovesicularsteatosis involved 40 to 70% of samples.The lobular hepatocytes showed prominent ballooning degeneration.Mallory Denk-hyaline bodies (MDBs) in four patients along with foci of lobular inflammation.The MDBs were observed by electron microscopy and stained by cytokeratin 18.The trichrome stain revealed bridging fibrosis.In family #1, there was a three-fold increase in Kupffer Cells in the eldest sibling with NASH compared to livers of the younger siblings.In addition, lipid droplets were more numerous and larger in the hepatocytes and the collagen deposits were 5 times larger compared to the siblings.In family #2, the older brother had cirrhosis, minimal inflammation and mild fatty infiltration while the younger had fatty infiltration with no inflammation or fibrosis.In family #3, large lipid droplets and collagen deposition were observed in the siblings, one of whom had HCC.Over 2-4 year follow up, all patients had progressive severity of NASH one of whom developed HCC.CONCLUSION: The special finding in livers of patients with NASH was accumulation of groups of Kupffer Cells, which was not associated with focal necrosis.It is postulated that collections of these perisinusoidal macrophages in NASH are a unique response to chronic portal endotoxemia or bacteremia.The persistent activation of these macrophages could lead to the chronic release of cytokines and contribute to chronic inflammation, fibrosis and cirrhosis leading to HCC.
Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin's lymphoma--a randomized multicenter study. The European Study Group of Erythropoietin (Epoetin Beta) Treatment in Multiple Myeloma and Non-Hodgkin's Lymphoma
Authors: A Osterborg, MA Boogaerts, R Cimino, U Essers, J Holowiecki, G Juliusson, G Jager, A Najman, D Peest
Journal: Blood (1996)
Patient-derived tumor xenografts in humanized NSG-SGM3 mice: A new immuno-oncology platform.
Authors: Li-Chin Yao, Jonathan Riess, Mingshan Cheng, Minan Wang, Jacques Banchereau, Lenny Shultz, Karolina Palucka, James G. Keck
Journal: Journal of Clinical Oncology (2016)

3074 Background: Humanized mice engrafted with tumors enable in vivo investigation of the interactions between the human immune system and human cancer. We have recently found that humanized NOD-scid IL2Rγnull(NSG) mice bearing patient-derived xenografts (PDX) allow efficacy studies of check-point inhibitors. Next generation NSG strains include triple transgenic NSG mice expressing human cytokines KITLG, CSF2, and IL-3 (NSG-SGM3). Methods: We provide a direct comparison of check-point inhibitors evaluation in NSG and NSG-SGM3 mice engrafted with CD34+ human hematopoietic progenitor cells (HPCs) from the same donor and implanted with PDX tumors. PDX tumors were engrafted into partially HLA-matched hu-NSG-SGM3 mice at 9 weeks post engraftment. Tumor-infiltrating myeloid cells were examined. Two PDX models and one cancer cell line with high PDL1 levels were used to test respond to anti-PD1 therapy in hu-NSG-SGM3 mice. Results: Reconstitution of human immune system in the blood was faster and more robust in NSG-SGM3 compared to NSG recipients throughout the course of the study (18 weeks). Human CD45+ cells reached 25% of total blood cells at week 4 in hu-NSG-SGM3 mice and at week 9 in hu-NSG mice. A majority of blood hCD45+ cells (55%) in hu-NSG-SGM3 at week 4 were CD33+ myeloid cells. By comparison, efficiency of human CD33+ cells (15%) in the circulation was poor in hu-NSG mice. Moreover, circulating hCD3+ T cells reached 10% at week 9 and included regulatory T cells (Tregs). Hu-NSG mice displayed comparable hCD3+ T cells in the blood only at 12-15 weeks and did not contain Tregs. Tumor-infiltrating myeloid cells will be discussed. High PD-1 expression by CD8+T cells and Tregs were present within the breast cancer microenvironment suggesting anergy and immunosuppression in hu-NSG-SGM3 mice. Treatment with the anti-PD-1 receptor antibody pembrolizumab significantly reduced tumor growth and the PD-1 expression level on lymphocytes. Conclusions: PDX-bearing hu-NSG-SGM3 mice might serve as a new and improved platform for preclinical immuno-oncology efficacy studies.
Race and Socioeconomic Factors Influencing Treatment Disparities and Comparative Effectiveness in Very Elderly Patients with Diffuse Large B-Cell Lymphoma
Authors: Gregory S. Calip, Sruthi Adimadhyam, Pritesh R. Patel, Karen Sweiss, Ashley B. Cha, Benjamin J. Nagy, Kellyn M. Moran, Sonali M. Smith, Brian C.-H. Chiu
Journal: Blood (2016)