tbuckley/cabot-search huggingface dataset:
OC-034 Probiotics for the prevention of antibiotic associated diarrhoea in the older inpatient population; a systematic review and meta-analysis
Authors: CA Parisinos, JL Ooi, JO Lindsay, GC Parkes
Journal: Gut (2015)

<h3>Introduction</h3> Probiotics are live microorganisms intended to confer a health benefit when consumed,<sup>1</sup>and have been advocated for the prevention of antibiotic associated diarrhoea (AAD). Older patients are more susceptible to AAD compared to the general adult population. We conducted a systematic review and meta-analysis of the literature on probiotic use for the prevention of AAD in this patient group. <h3>Method</h3> Two independent reviewers identified and critically appraised randomised controlled trials (RCTs) of probiotics from electronic databases PubMed and EMBASE (from date of inception to Jan 2015) for the prevention and treatment of AAD in hospital patients with mean age &gt;60 years. <h3>Results</h3> Eleven RCTs met inclusion criteria. The pooled relative risk (RR) in a DerSimonian-Laird random-effects meta-analysis of 11 RCTs, which included 4292 participants, showed a reduction in AAD (RR 0.67, 95% confidence interval (CI), 0.48 to 0.95; p = 0.02; <i>I</i><sup>2</sup>= 64%). Subgroup genus analysis demonstrated a significant risk reduction with only Lactobacillus based probiotics (RR 0.51, CI 0.39 to 0.67, p &lt; 0.00001, <i>I</i><sup>2</sup>= 0%). Only 3/11 demonstrated adequate power. Adverse events were reported in only 6/11 RCTs, with no serious events attributed to probiotic use. <h3>Conclusion</h3> Pooled results demonstrate that probiotics are associated with a risk reduction in AAD in older inpatients. Subgroup analysis demonstrated that this benefit is derived from Lactobacillus-only probiotics, an attractive candidate for future research. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> FAO, WHO. Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. 2001. ftp://ftp.fao.org/ed/esn/food/probio_report_en.pdf
Use of Ras effector RASSF1A promoter gene methylation and chromosome 9p loss of heterozygosity (LOH) to predict progression-free survival (PFS) in perioperative chemotherapy (CT) phase III trial IFCT-0002 in resectable non-small cell lung cancer
Authors: G. Zalcman, M. Beau-Faller, C. Creveuil, F. de Fraipont, M. Mounawar, N. Richard, E. Bergot, M. Favrot, F. Morin, B. Milleron
Journal: Journal of Clinical Oncology (2008)

7500 Background: IFCT-0002 phase 3 trial compared two timings of CT in early lung cancer, all before surgery (PRE) versus PERIoperative, and two CT regimens, CDDP-Gem vs. CBDCA-Pac. 528 patients were randomized. Early results showed no difference between the two CT regimens for response rate or tolerance, but a better compliance in PRE vs. PERI arm. We hypothesized that molecular markers could help to define the subgroups that did not beneficiate from CT. Methods: Molecular alterations in key pathways regulating G1/S transition or apoptosis were screened. TP53, EGFR and K-RAS mutations, RASSF1A, DAPK, ECAD, FHIT, TIMP3 and p16 promoter gene methylation, 3p, 17p and 9p LOH were evaluated in 178 patients with snap-frozen tissue collected at time of surgery. Results: K-ras mutations identified in 16.3% of patients, was the only molecular alteration associated with the absence of tumor response to chemotherapy (crude RR = 2.13 95%CI [1.11–4.55], p=0.019). However, K-ras mutations were not associated with PFS (p=0.89). RASSF1A promoter gene methylation found in 22.2% of patients was not mutually exclusive with K-Ras mutations. Although not associated with tumor response, RASSF1A promoter gene methylation (adjusted HR = 2.34 95%CI [1.46–3.75], p=0.0013) and 9pLOH (adjusted HR = 2.28 95%CI [1.25–4.15], p=0.015) predicted a worse PFS independently of T, Stage, PS and histology, with respectively 14 vs. 64 months and 18 vs. 36 months of median PFS. Alterations of both RASSF1A and 3p LOH, or RASSF1A plus FHIT methylation or 3p LOH, also predicted a worse PFS (respective adjusted HR 2.46 and 2.22, p= 0.024 and 0.031). There only was a non significant trend for alterations of both p53 and 17p, predicting a worse PFS (18 vs. 36 months of median PFS, p=0.13), with a negative impact for disruptive p53 mutations. Conclusions: This study showed a negative prognostic impact for alterations of RASSF1A in early lung cancer. In resectable patients receiving neoadjuvant CT, a limited set of apoptosis or proliferation alterations could represent strong negative prognostic factors. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly France Eli Lilly
Group-Level Symptom Networks in Depression
Authors: Elisabeth H. Bos, Rob B. K. Wanders
Journal: JAMA Psychiatry (2016)

To the Editor About 8 years ago, network models entered the field of psychiatry. 1 In this approach, psychiatric disorders are conceptualized as a dynamic interplay between symptoms over time, contrasting the traditional disease model of an underlying common cause.With the intention to describe how symptoms give rise to each other, the network approach would deal with processes taking place at the level of the individual. 1 Nevertheless, almost all studies on networks have investigated this phenomenon at the group level.The latest example is a study by van Borkulo et al. 2 This study showed that the sparse symptom network of a group of patients with persistent depression was more densely connected at baseline than the network of the remitted group.The authors argued that more strongly connected symptoms imply higher vulnerability to depression because of stronger feedback among the symptoms.Here they jump from the population to the individual level in their reasoning, without good arguments.Their group-level networks show whether symptoms co-occur across cases.The very fact that symptoms tend to co-occur does not imply that they influence each other over time within individuals.Symptoms may co-occur for several reasons including a common underlying cause.The fact that the difference in network connectivity largely disappeared when severity and level of functioning was partialled out is suggestive.Only in the minimally sparse networks was the difference preserved.The authors did mention the limitation that their networks are based on between-subject variance, but suggest this is not problematic as long as the groups are homogenous.We think the problem is more fundamental because associations at the population level may be radically different from associations at the individual level even in the case of homogeneity.This phenomenon, called the ecological fallacy or Simpson's paradox, 3 may occur rather often, as was shown in an excellent review 4 (with 2 authors of the van Borkulo et al 1 article as coauthors).Therefore, drawing inferences from patterns observed between people to processes that occur within people is unwarranted.However, we have a natural tendency to do so, and the visually attractive network graphs enhance this tendency.We think it is time to investigate networks at the proper level of investigation (ie, at the intraindividual level).As long as we keep investigating cross-sectional group-level networks, the results will remain compatible with a traditional disease model, will not be informative of symptom interactions within individuals, and will obscure scientific reasoning.
The role of radiation therapy in the management of hemangiomas of the liver
Authors: W. C. Park
Journal: JAMA (1970)

Five cases of nonresectable hemangioma of the liver were treated with radiation therapy. Four of the five patients had good results with both control of disease and preservation of normal liver function. We suggest that radiation therapy provides an effective method of managing nonresectable hemangiomas of the liver or those resectable hemangiomas where there is an appreciable operative risk.
Molecular evolution of mammalian lactate dehydrogenase-A genes and pseudogenes: association of a mouse processed pseudogene with a B1 repetitive sequence.
Authors: K M Fukasawa, W H Li, K Yagi, C C Luo, S S Li
Journal: Molecular Biology and Evolution (1986)

A mouse genomic clone containing a lactate dehydrogenase-A (LDH-A) processed pseudogene and a B1 repetitive element was isolated, and a nucleotide sequence of approximately 3 kb was determined. The pseudogene and B1 element are flanked by perfect 13-bp repeats, and the B1 sequence starts at 14 nucleotides 3' to the presumptive polyadenylation signal of the pseudogene. The nucleotide sequences of the LDH-A genes and processed pseudogenes from mouse, rat, and human were compared, and a phylogenetic tree was constructed. The rate and pattern of nucleotide substitutions in the LDH-A pseudogenes are similar to previously reported results (Li et al. 1984). The average rate of nucleotide substitutions in the LDH-A pseudogenes is 4.3 X 10(-9)/site/year. The substitutions of C----T and G----A are most frequent, and A----G substitutions are relatively high. The rate of synonymous substitutions in the LDH-A genes is 5.3 X 10(-9), which is not significantly higher than the average rate of 4.7 X 10(-9) for 35 mammalian genes. The rate of nonsynonymous substitutions in the LDH-A genes is 0.20 X 10(-9), which is considerably lower than the average rate of 0.88 X 10(-9) for 35 mammalian genes. Thus, the mammalian LDH-A gene appears to be highly conserved in evolution.
Origin of structural domains of the serum-albumin gene family and a predicted structure of the gene for vitamin D-binding protein.
Authors: P E Gibbs, A Dugaiczyk
Journal: Molecular Biology and Evolution (1987)

We have recently determined complete DNA sequences for the human albumin and alpha-fetoprotein [AFP] genes and thus have identified their detailed structures. Each is composed of three domains of four exons, three of which are internal and one of which is a domain-linking exon. Equivalent exons in each domain show sufficient sequence and structural similarity to be considered homologous; additional unique exons at each end of the gene show no similarity to the internal triplicated structures. Since earlier, conflicting evolutionary models were based on analysis of single gene structures, we derived from five genes a series of consensus sequences representing the three internal exons as well as the domain-linking exon. The five genes were human and rat albumin and human, mouse, and rat AFP genes. Structurally equivalent exons of the different domains are shown to have arisen from a single exon in a one-domain precursor. Exons that bridge the domains arose from an unequal crossover that fused two exons of the precursor. Our model suggests that part of the coding sequence of the one-domain precursor may have been derived from an intron, by way of loss of a splice site. The consensus sequences were used to propose an intron-exon structure for the related gene encoding the serum vitamin D-binding protein (DBP). DBP is truncated relative to albumin and AFP, and we submit that this results from deletion of two internal exons in the third domain of the gene rather than from premature termination of the coding sequence.
Natural Killer Cell Licensing Delineates NK “Helper/Repair” and NK “Effector/Suppressor” Subsets During Viral Infections
Authors: Can M. Sungur, Anthony E. Zamora, Ethan G. Aguilar, Yajarayma Tang-Feldman, Juan Du, Nicole Baumgarth, Mingyi Chen, Claire Pomeroy, Jeffrey M. Venstrom, William J. Murphy
Journal: Blood (2013)
Interactions Between PD-1 and PD-L1 and PD-L2 Promote Malignant B-Cell Growth in Waldenstrom Macroglobulinemia
Authors: Deanna M. Grote, Steven C. Ziesmer, Lucy S. Hodge, Tammy L. Price-Troska, Anne J. Novak, Zhi-Zhang Yang, Stephen M Ansell
Journal: Blood (2013)
Differences in Bone Quality between High versus Low Turnover Renal Osteodystrophy
Authors: Daniel S. Porter, David Pienkowski, Marie-Claude Faugere, Hartmut H. Malluche
Journal: Journal of the American Society of Nephrology (2012)

Abnormal bone turnover is common in chronic kidney disease (CKD), but its effects on bone quality remain unclear. This study sought to quantify the relationship between abnormal bone turnover and bone quality. Iliac crest bone biopsies were obtained from CKD-5 patients on dialysis with low (n=18) or high (n=17) turnover, and from volunteers (n=12) with normal turnover and normal kidney function. Histomorphometric methods were used to quantify the microstructural parameters; Fourier transform infrared spectroscopy and nanoindentation were used to quantify the material and mechanical properties in bone. Reduced mineral-to-matrix ratio, mineral crystal size, stiffness and hardness were observed in bone with high turnover compared to bone with normal or low turnover. Decreased cancellous bone volume and trabecular thickness were seen in bone with low turnover compared to bone with normal or high turnover. Bone quality, as defined by its microstructural, material, and mechanical properties, is related to bone turnover. These data suggest that turnover related alterations in bone quality may contribute to the known diminished mechanical competence of bone in CKD patients, albeit from different mechanisms for bone with high (material abnormality) vs. low (microstructural alteration) turnover. The present findings suggest that improved treatments for renal osteodystrophy should seek tomore » avoid low or high bone turnover and aim for turnover rates as close to normal as possible.« less
Abstract 48: A Multicenter Prospective Cohort Study on a Novel Neurological Prognostic Index, Regional Brain Oxygen Saturation, in Patients with Out-of-Hospital Cardiac Arrest
Authors: Noritoshi Ito, Tatsuro Kai, Ayumu Tsuruoka, Yosuke Honma, Hideto Yasuda, Masahiro Mizobuchi, Noriaki Yamada, Masafumi Otsuka, Masayuki Fujioka, Tomoyuki Endo, Tomohiko Orita, Takashi Unoki, Kei Hayashida, Takaya Morooka, Kei Nishiyama, Yasuji Doi, Issei Komuro
Journal: Circulation (2012)

BACKGROUNDS: A reliable and readily available neurological prognostic index for the cerebral resuscitation of out-of-hospital cardiac arrest (OHCA) patients (pts) is required. We have previously reported in a single center cohort study of OHCA pts that regional brain oxygen saturation (rSO 2 ) measured on hospital arrival may help predict neurological outcomes. OBJECTIVE: To compare the power of rSO 2 and conventional indexes−lactate, base excess (BE), and ammonia (NH 3 )−measured on hospital arrival to prognose neurological outcomes at 30 days after cardiac arrest that are assessed according to the cerebral performance category (CPC) criteria in a multicenter prospective cohort study. METHODS: The database of the J-POP registry (conducted at 14 tertiary emergency hospitals in Japan) has prospectively enrolled 764 OHCA pts. Of these pts, 596 (77.5%) who were examined for rSO 2 , lactate, BE, and NH 3 were analyzed in the present study. The exclusion criteria included 1) trauma, 2) accidental hypothermia, 3) age under 18, 4) do not attempt resuscitation order, 5) Glasgow Coma Scale &gt; 8 on hospital arrival, and 6) missing data. Immediately after hospital arrival, rSO 2 was measured using a near-infrared spectroscopy device (INVOS; Covidien, USA) placed on the forehead, along with the measurement of lactate, BE, and NH 3 . Regardless of the rSO 2 readings, all pts received the best available therapy. RESULTS: Among 596 OHCA pts, 31 (5.2%) had good neurological outcome. The areas under the curve (AUCs) for the prognostic indexes-rSO 2 , lactate, BE, and NH 3 −were 0.912, 0.794, 0.773 and 0.853, respectively (Table). The AUC was significantly greater for rSO 2 than for lactate ( p = 0.0001) or BE ( p = 0.0057) and tended to be greater for NH 3 ( p = 0.0844). CONCLUSIONS: Compared with the conventional neurological prognostic indexes, rSO 2 may be more reliable for neurological prognostication based on its specificity, positive predictive value, and AUC.
The NCIC CTG and AGITG CO.23 trial: A phase III randomized study of BBI608 plus best supportive care (BSC) versus placebo (PBO) plus BSC in patients (Pts) with pretreated advanced colorectal carcinoma (CRC).
Authors: Derek J. Jonker, Louise M. Nott, Takayuki Yoshino, Chiang Li, Sharlene Gill, Jeremy David Shapiro, Atsushi Ohtsu, John Raymond Zalcberg, Michael M. Vickers, John Simes, Alice Chia-chi Wei, Nicole Mittmann, Nadine M Magoski, Yvonne Murray, Eric Tsobanis, Dongsheng Tu, David Kerstein, Christopher J. O'Callaghan
Journal: Journal of Clinical Oncology (2014)

TPS3660 Background: BBI608 is an orally-administered first-in-class cancer stemness inhibitor which blocks cancer stem cell (CSC) self-renewal and induces cell death in CSCs as well as non-stem cancer cells by inhibition of the Stat3, β-catenin and Nanog pathways. Encouraging signs of anti-cancer activity, particularly in colorectal carcinoma (CRC), were observed in a phase I dose escalation study: disease control in 8/12 (67%) evaluable patients (pts); median progression free survival (PFS) equals 14 weeks; median overall survival (OS) equals 47 weeks (Langleben et al. J Clin Oncol 2013; 31 suppl; abstr 2542). Similar activity in CRC pts was observed in a subsequent phase I/II extension study. On the basis of these data, a phase III trial was designed and is being conducted by the National Cancer Institute of Canada (NCIC) Clinical Trials Group and the Australasian Gastrointestinal Trials Group under special protocol assessment with the FDA. Methods: This randomized, double-blind, placebo (PBO)-controlled study (ClinicalTrials.gov NCT01830621) will assess the efficacy and safety of BBI608+best supportive care (BSC) versus PBO+BSC in pts with metastatic or advanced, unresectable, refractory CRC (target n=650). Pts have no remaining approved therapies available, having failed standard chemotherapy based regimens containing a fluoropyrimidine, irinotecan and oxaliplatin (and an EGFR inhibitor, if KRAS wild type). Pts are randomized in a 1:1 ratio to receive BBI608 480 mg or matching PBO twice daily continuously. Treatment will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Primary endpoint is OS; secondary endpoints include disease control rate, PFS, safety, and quality of life. Analysis will be according to randomized group stratified by Eastern Cooperative Oncology Group performance status (0 vs. 1), KRAS status (wild type vs. mutant), prior anti-vascular endothelial growth factor therapy (yes vs .no), and time from diagnosis of metastatic disease to randomization (<18 vs. ≥18 months). In addition blood, plasma, and archival tissue will be assessed for pharmacokinetic and biomarker analyses and health utility will be measured. As of February 2014, 130 pts were randomized and recruitment is ongoing in Canada, Australia, New Zealand and Japan. Clinical trial information: NCT01830621.
Sister Chromatid Exchange Frequency in Asbestos Workers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: W N Rom, G K Livingston, K R Casey, S D Wood, M J Egger, G L Chiu, L Jerominski
Journal: JNCI Journal of the National Cancer Institute (1983)

In vitro cytogenetic studies of amosite, chrysotile, and crocidolite asbestos have shown that these fibers may induce chromosome abnormalities and an elevated sister chromatid exchange (SCE) rate in mammalian cells. Twenty-five asbestos insulators (6 with radiographic asbestosis) were compared to 14 controls frequency matched for age and were found to have a marginally increased SCE rate in circulating lymphocytes with increasing years of exposure (P= 0.057). There was a significant association between SCE rate and smoking (P=0.002) after controlling for years of asbestos exposure and age. Smoking asbestos insulators had the highest SCE rate. Sister chromatid exchanges in chromosomes of group A, i.e., the group with the longest chromosomes, were significantly associated with asbestos exposure and cigarette smoking, with an interaction between the two.
Outbreaks of gastroenteritis linked to lettuce, Denmark, January 2010
Authors: S Ethelberg, M Lisby, B Böttiger, A C Schultz, A Villif, T Jensen, K E Olsen, F Scheutz, C Kjelsø, L Muller
Journal: Eurosurveillance (2010)

At least 11 linked outbreaks of gastroenteritis with a total of 260 cases have occurred in Denmark in mid January 2010. Investigations showed that the outbreaks were caused by norovirus of several genotypes and by enterotoxigenic Escherichia coli. Lettuce of the lollo bionda type grown in France was found to be the vehicle.
Clinico-Biological Characteristics of Patients Surviving More Than Two Years with Recurrent and/or Metastatic (R/M) Cancer: Results of a Transversal National Multicentric Survey
Authors: D. Loirat, C. Tlemsani, F. Legouté, C. Renaudin-Fonsegrive, J. Arrondeau, D. Lopez-Trabada, M. Cabart, M. Alt, C. Helissey, E. Boissier, L. Verlingue, E. Grignano, A. Bellesoeur, C. Le Tourneau, B.J. Rousseau
Journal: Annals of Oncology (2014)
Autoimmune inner ear disease in a melanoma patient treated with pembrolizumab
Authors: Matthew Zibelman, Natasha Pollak, Anthony J Olszanski
Journal: Journal for ImmunoTherapy of Cancer (2016)

Immune related adverse events affecting various organ systems are a recognized potential consequence of immune checkpoint inhibition. However, autoimmune inner ear disease is one complication not previously associated with the use of checkpoint inhibitors, though it has been reported after adoptive cell immunotherapy.Here we present what we believe is the first case of autoimmune inner ear disease resulting from treatment with an immune checkpoint inhibitor in a patient with metastatic melanoma. An 82 year old male presented with widespread metastatic mucosal melanoma and was initially treated with the CTLA-4 inhibitor ipilimumab but had progression of disease after four doses. He was subsequently treated with the PD-1 inhibitor pembrolizumab and after two doses the patient noted bilateral hearing loss. Otology evaluation was significant for the development of bilateral sensorineural hearing loss and the patient was started on treatment with bilateral intratympanic dexamethasone injections. He experienced significant recovery of his hearing deficit with the intratympanic injections and restaging imaging after 12 weeks of pembrolizumab demonstrated a dramatic reduction in tumor burden.Autoimmune inner ear disease has been previously associated with the therapeutic transfer of genetically engineered lymphocytes as an on-target effect of donor T-cells recognizing antigens on cells in the inner ear. It is important for physicians to have a high clinical index of suspicion for the appropriate recognition and management of any potential autoimmune toxicity with checkpoint inhibitors given the variability of presentation and unique aspects of toxicity.