tbuckley/cabot-search huggingface dataset:
P216 Duration of total and exclusive breastfeeding, timing of solid food introduction and risk of allergic diseases: a systematic review and meta-analysis
Authors: V Garcia-Larsen, D Ierodiakonou, J Leonardi-Bee, T Reeves, J Chivinge, Z Robinson, K Jarrold, N Geoghegan, E Andreou, N Tagiyeva-Milne, U Nurmatov, S Cunha, RJ Boyle
Journal: Thorax (2015)

<h3>Background</h3> Allergic diseases are the leading causes of chronic illness in children and young adults in the UK. <h3>Aim</h3> To undertake a comprehensive review of the evidence on the effect of breastfeeding (BF) duration and timing of solid food introduction (SFI), on the risk of wheeze, atopic dermatitis, rhino-conjunctivitis, food allergy, allergic sensitisation and measures of lung function or bronchial hyper-responsiveness. <h3>Methods</h3> We carried out a systematic review following the PRISMA guidelines (International Prospective Register of Systematic Reviews [PROSPERO] CRD42013003802). We included intervention, cohort, case-control and cross-sectional studies. Following literature searches (July 2013), study eligibility, data extraction and risk of bias assessments were conducted independently by two investigators. Random effects meta-analyses were used to pool results. Five levels of comparison of total or exclusive BF duration were used to assess disease risk in children at age 0–4 yrs, 5–15 yrs or 15+yrs: ‘never vs ever’,’≥1–2 months vs. &lt;1–2 months’, ‘≥3–4 months vs. &lt;3–4 months’, ‘≥5–7 months vs. &lt;5–7 months’, and ‘≥8–12 months vs. &lt;8–12 months’. Exclusive BF (EBF; BF without formula or solid food supplementation) was categorised as ‘≥0–2 months vs. &lt;0–2 months’, ‘≥3–4 months vs. &lt;3–4 months’ and ‘≥5+ months vs. &lt;5+ months’, and SFI as ‘≥3–4 months vs. &lt;3–4 months’. Publication bias was assessed using Egger’s asymmetry test. <h3>Results</h3> Of 16,289 identified studies, 564 met the inclusion criteria and were eligible for analysis. We found reduced risk of wheezing in children aged 5–14 yrs with longer BF or EBF duration, which was dose-dependent, but there was evidence of publication bias (BF and odds of recurrent wheezing P = 0.007). Similar results were found for recurrent wheeze at age 5–14 yrs but not in other ages. Measures of lung function were also increased with increased BF or EBF duration. We found no evidence that BF duration influences other allergic outcomes, and no evidence that timing of SFI influences any of the outcomes assessed. <h3>Conclusion</h3> Longer breastfeeding duration may protect against wheezing later in childhood. Any effect is likely to be through effects on lung function rather than allergic sensitisation. Other allergic outcomes do not appear to be influenced by breastfeeding duration.
Prevention of Necrotizing Enterocolitis in Low-Birth-Weight Infants by IgA–IgG Feeding
Authors: Martha M. Eibl, Hermann M. Wolf, Heinz Fürnkranz, Alfred Rosenkranz
Journal: New England Journal of Medicine (1988)

In a randomized clinical trial, we evaluated the efficacy of an oral immunoglobulin preparation (73 percent IgA and 26 percent IgG) in reducing the incidence of necrotizing enterocolitis in infants of low birth weight for whom breast milk from their mothers was not available. A total of 434 infants weighing between 800 and 2000 g were eligible for entry in the study. Of these, 255 were withdrawn — 234 during the first week of the study because breast milk from their mothers became available (123 in the treatment group and 111 in the control group), and 21 because of violations of protocol or because breast milk became available after the first week. The duration of follow-up was 28 days. Among the infants for whom breast milk did not become available during the study, there were no cases of necrotizing enterocolitis among the 88 receiving oral IgA–IgG, as compared with six cases among the 91 control infants (P = 0.0143). Of the infants withdrawn from the study, two assigned to the control group had necrotizing enterocolitis. We conclude that the oral administration of IgA–IgG may prevent the development of necrotizing enterocolitis in low-birth-weight infants. (N Engl J Med 1988; 319:1–7.)
ATCT-21A PROSPECTIVE PHASE II CLINICAL TRIAL OF 5-AMINOLEVULINIC ACID TO CORRELATE INTRAOPERATIVE FLUORESCENCE INTENSITY WITH HISTOLOGIC CELLULARITY
Authors: Darryl Lau, Shawn Hervey-Jumper, Susan Chang, Annette Molinaro, Michael McDermott, Joanna Phillips, Mitchel Berger
Journal: Neuro-Oncology (2015)

There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. A phase II clinical trial was undertaken to correlate the intensity of 5-aminolevulinic acid (ALA) fluorescence with degree of tumor cellularity during resection of high grade gliomas. A single-center, single arm, phase II clinical trial of ALA fluorescence-guided resection of high grade gliomas was held from 2010 to 2014. Biopsies were graded on a 4 point scale (0-none to 3-highest) based on ALA fluorescence intensity by the neurosurgeon and independently based on tumor cellularity by a neuropathologist. Outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity and adverse events. A total of 211 biopsies from 59 patients were included: 79.7% glioblastoma. ALA intensity 3 correlated with tumor presence 97.4% of cases and ALA intensity 0 correlated with tumor absence only 37.7% of cases. For all tumor types, glioblastoma, high grade, and recurrent tumors, ALA fluorescence intensity 3 correlated strongly with cellularity grade 3; correlation coefficients were 0.65, 0.66, 0.65, and 0.62, respectively. Specificity and PPV of ALA intensity 3-cellularity grade 3 match ranged from 95% to 100% and 86% to 100%, respectively. In samples without tumor, 35.4% had ALA fluorescence. Of those, 90.9% contained reactive astrocytes and atypical cells; 8.1% were normal brain. In non-fluorescent samples, 62.3% had tumor cells present. ALA associated complication was 3.4%. ALA demonstrated high PPV and ALA intensity 3 correlated strongly with cellularity grade 3. However, ALA had low NPV for excluding tumor presence. In addition, even in the absence of tumor cells, reactive changes including inflammation may lead to ALA fluorescence.
Nonconcurrence in Abstracted Diagnoses of Non-Hodgkin's Lymphoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F R Dick, S F VanLier, K McKeen, G D Everett, A Blair
Journal: JNCI Journal of the National Cancer Institute (1987)

The availability of two independent sets of abstracted diagnoses on 289 cases of non-Hodgkin's lymphoma (NHL), one from the Iowa Surveillance, Epidemiology, and End Results (SEER) Program and the other from an epidemiologic study in Iowa of factors affecting rural males (FARM), allowed us to determine the disagreement between abstracted diagnoses. For both sets the reported diagnosis was translated to International Classification of Disease for Oncology terminology and then to the Working Formulation (WF). Comparison of the WF diagnoses between the FARM study and the SEER Program showed disagreement in 68 of 290 cases (23.4%). Apparent causes of disagreement were as follows: coding errors-9 cases, unconventional or ambiguous terminology on reports resulting in different interpretation of the NHL subtype--30 cases, differences in coding rules for the FARM study and SEER Program--9 cases, acquisition of different reports with different diagnoses on the same case by the FARM study and SEER Program--20 cases. Several corrective measures that might successfully decrease the incidence of disagreement include: education of pathologists in the use of conventional terminology, and use of the category "unclassifiable" when abstracting reports with unconventional or ambiguous terminology. This 23.4% disagreement rate in the abstracting method adds to the known problem of nonconcurrence in the pathologic diagnosis of subtypes of NHL.
Case 35-2010
Authors: William A. Kormos, Carol C. Wu, John A. Branda, Adriano Piris
Journal: New England Journal of Medicine (2010)

A 56-year-old man was admitted to the hospital because of cough, hypoxemia, and rash. Nine days before admission, myalgias, chills, sweats, fatigue, and a dry cough developed, with a rash over the chest and flanks.
Survival, safety, and response patterns in a phase 1b multicenter trial of talimogene laherparepvec (T-VEC) and ipilimumab (ipi) in previously untreated, unresected stage IIIB-IV melanoma.
Authors: Igor Puzanov, Mohammed M. Milhem, Robert Hans Ingemar Andtbacka, David R. Minor, Omid Hamid, Ai Li, Jeffrey Chou, Howard Kaufman
Journal: Journal of Clinical Oncology (2015)

9063 Background: T-VEC is an HSV-derived oncolytic immunotherapy designed to induce systemic antitumor immunity. In a phase 3 melanoma study, T-VEC monotherapy significantly improved durable response rate (DRR, ≥ 6 month response) vs GM-CSF (16% vs 2%, P < 0.0001; Andtbacka et al. ASCO 2013), and median OS was 4.4 months longer for T-VEC vs GM-CSF (23.3 vs 18.9 months; HR = 0.79, 95% CI: 0.62-1.00; P= 0.051; Kaufman et al, ASCO 2014). Combining T-VEC to promote tumor-derived antigen release with an immune checkpoint inhibitor may enhance efficacy compared to either agent alone. The phase 1b portion of this phase 1b/2 combination study (NCT01740297) completed enrollment and met its primary objective with no dose-limiting toxicities (DLTs) and an objective response rate (ORR) of 56% (Puzanov et al. ASCO 2014). Methods: Key inclusion criteria included stage IIIB-IV melanoma; no prior systemic treatment; measurable disease; and ≥ 1 injectable cutaneous, subcutaneous, or nodal lesion. T-VEC was given intralesionally at ≤ 4 mL of 106 PFU/mL at week 1, then 108 PFU/mL at week 4, and then Q2W. Ipi 3 mg/kg Q3W was given as 4 infusions starting week 6. T-VEC continued until DLT, intolerance, all injectable tumors disappeared, or disease progression (PD) per immune-related response criteria (irRC). Results: The data cutoff was Dec 22, 2014 with all patients at least 17 months from start of treatment. 18 patients received T-VEC+ipi; grade 3/4 treatment-emergent AEs occurred in 32% and grade 3/4 immune-related AEs occurred in 2 patients with no treatment-related deaths. Per irRC, ORR was 56% (33% CR) and DRR was 44%. Median time to response was 5.3 months (range 2.6-5.7). Median progression-free survival (PFS) was 10.6 months (2.6-19.3+). Median overall survival (OS) was not reached; 12-month and 18-month survival were 72.2% and 67%. On a lesion level, 24 and 11 of 35 injected index lesions and 8 and 5 of 16 uninjected index lesions regressed ≥ 50% and 100%, respectively. Conclusions: At > 17 months, T-VEC+ipi continued to demonstrate durable responses with 2/3 of patients alive at 18 months and no new safety signals. Phase 2 (ipi vs T-VEC+ipi) is ongoing. Clinical trial information: NCT01740297.
8P EGFR, KRAS, BRAF, and PI3K mutations and ALK rearrangement in 327 consecutive Spanish non-squamous NSCLC patients
Authors: P. Martin Martorell, M. Huerta, A. Compañ Quilis, M. Abellán, S. Blesa, F. Chaves, D. Dualde Beltrán, A. Fernández Do Nascimento, A. Insa
Journal: Journal of Thoracic Oncology (2016)
P46 Frequency of COPD exacerbations in the German DACCORD Registry
Authors: P Kardos, R Buhl, C-P Criée, C Vogelmeier, C Mailaender, H Worth
Journal: Thorax (2015)

<h3>Introduction</h3> In patients with COPD, exacerbations are among the most relevant safety measures. In this analysis of data from the observational DACCORD study, we report the frequency of exacerbations in a COPD population. <h3>Methods</h3> To get insights into occurrence and frequency of exacerbations, data from 4,123 patients were obtained from 349 primary and secondary care centres in Germany. To be eligible for entry into DACCORD, all patients had to have a COPD diagnosis (consistent with the German Disease Management Programme definition), and had to have a change in bronchodilator maintenance medication, prior to entry. Data collected included history and treatment of exacerbations 6 months prior to inclusion, and for the duration of follow-up. Exacerbations were defined based on prescription of oral corticosteroids and/or antibiotics or on hospitalisation. <h3>Results</h3> Mean age of the patients was 65.7 years; 36.9% of patients had severe or very severe airflow limitation (GOLD 2010). In the 6 month period prior to study inclusion, 26.4% of the patients had at least one exacerbation. Fewer patients in the subgroup with CAT30 (16.7% vs 47.9%). Interestingly, 45% of all exacerbators received inhaled corticosteroids (ICS) compared to 38.7% of the non-exacerbators. ICS treatment in patients with an exacerbation history in the 6 months prior to study inclusion was more frequent in patients with a duration of disease &gt;1 year compared to those with disease duration In the interim-analysis of 4,123 patients that have completed the 1st year of the observational period, 25.5% had at least one exacerbation during follow-up. In the subgroups CAT30, 22.0% and 40.2% of the patients had at least one exacerbation, respectively. A hospital stay was required for 3.5% of the patients who experienced an exacerbation of the total cohort during 12 months follow-up compared to 4.3% in the 6 month prior to the study. <h3>Conclusion</h3> At baseline, the prevalence of patients reporting at least one exacerbation in this large real life COPD cohort was low and seems to be unchanged during 1 year follow-up.
Civil commitment standards and patient mix in England/Wales, Italy, and the United States
Authors: S P Segal
Journal: American Journal of Psychiatry (1989)

Although England/Wales, Italy, and the United States share a common policy of deinstitutionalization, their mental health systems differ considerably. Each country's civil commitment standards define patient eligibility criteria along one of two primary dimensions--need for treatment or degree of dangerousness. These differential selection criteria result in mental health systems serving different subgroups of the total population. The criteria in England/Wales target older women; in the United States, younger men; and in Italy, a group balanced in age and sex. Implications for the current debate on civil commitment policies are considered.
Methotrexate: Distribution in Cerebrospinal Fluid after Intravenous, Ventricular and Lumbar Injections
Authors: William R. Shapiro, Dean F. Young, Bipin M. Mehta
Journal: New England Journal of Medicine (1975)

The kinetics and distribution of methotrexate in intraventricular and intrathecal cerebrospinal-fluid spaces were studied in patients with meningeal leukemia and meningeal carcinomatosis after drug administration by intravenous infusion, indwelling intraventricular subcutaneous reservoir (Ommaya), or standard lumbar puncture. Negligible ventricular concentrations followed a single intravenous dose. During an intravenous infusion (500 mg per square meter for 24 hours) the ventricular cerebrospinal-fluid concentration rose to 6 times 10-minus 7 M. Methotrexate administered by Ommaya reservoir, at a dose of 6.25 mg per square meter, rapidly distributed in the subarachnoid space; the peak ventricular concentration of 2 times 10-minus 4 M declined exponentially over 48 hours. Lumbar cerebrospinal-fluid concentration reached a maximum of 5 times 10-minus 5 M four hours after injection and then fell exponentially. Administration by lumbar puncture occasionally produced epidural and subdural leakage; even with successful lumbar puncture, ventricular methotrexate concentration varied considerably from patient to patient despite similar doses. Administration by Ommaya reservoir more reliably produced adequate cerebrospinal fluid distribution than administration by lumbar puncture.
Vocal-Cord Dysfunction Presenting as Asthma
Authors: Kent L. Christopher, Raymond P. Wood, R. Christa Eckert, Florence B. Blager, Roy A. Raney, Joseph F. Souhrada
Journal: New England Journal of Medicine (1983)

We identified five patients with a functional disorder of the vocal cords that mimicked attacks of bronchial asthma. Paroxysms of wheezing and dyspnea were refractory to standard therapy for asthma. During episodes of wheezing, the maximal expiratory and inspiratory flow–volume relationship was consistent with a variable extrathoracic obstruction. Laryngoscopy confirmed that wheezing was due to adduction of the true and false vocal cords throughout the respiratory cycle. During asymptomatic periods the maximal flow–volume relationship and laryngoscopic examination were normal. Provocation tests for bronchial asthma were negative. A variety of personality styles and psychiatric diagnoses were represented; patients were not aware of the vocal-cord dysfunction, which uniformly and dramatically responded to speech therapy and psychotherapy. This syndrome may be a form of conversion reaction. (N Engl J Med 1983; 308:1566–70.)
miR-141-Mediated Regulation of Brain Metastasis From Breast Cancer
Authors: Bisrat G. Debeb, Lara Lacerda, Simone Anfossi, Parmeswaran Diagaradjane, Khoi Chu, Arvind Bambhroliya, Lei Huo, Caimiao Wei, Richard A. Larson, Adam R. Wolfe, Wei Xu, Daniel L. Smith, Li Li, Cristina Ivan, Pamela K. Allen, Wenhui Wu, George A. Calin, Savitri Krishnamurthy, Xiang H. Zhang, Thomas A. Buchholz, Naoto T. Ueno, James M. Reuben, Wendy A. Woodward
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Brain metastasis poses a major treatment challenge and remains an unmet clinical need. Finding novel therapies to prevent and treat brain metastases requires an understanding of the biology and molecular basis of the process, which currently is constrained by a dearth of experimental models and specific therapeutic targets. Methods: Green Fluorescent Protein (GFP)-labeled breast cancer cells were injected via tail vein into SCID/Beige mice (n = 10-15 per group), and metastatic colonization to the brain and lung was evaluated eight weeks later. Knockdown and overexpression of miR-141 were achieved with lentiviral vectors. Serum levels of miR-141 were measured from breast cancer patients (n = 105), and the association with clinical outcome was determined by Kaplan-Meier method. All statistical tests were two-sided. Results: Novel brain metastasis mouse models were developed via tail vein injection of parental triple-negative and human epidermal growth factor receptor 2 (HER2)–overexpressing inflammatory breast cancer lines. Knockdown of miR-141 inhibited metastatic colonization to brain (miR-141 knockdown vs control: SUM149, 0/8 mice vs 6/9 mice, P = .009; MDA-IBC3, 2/14 mice vs 10/15 mice, P = .007). Ectopic expression of miR-141 in nonexpressing MDA-MB-231 enhanced brain metastatic colonization (5/9 mice vs 0/10 mice, P = .02). Furthermore, high miR-141 serum levels were associated with shorter brain metastasis–free survival (P = .04) and were an independent predictor of progression-free survival (hazard ratio [HR] = 4.77, 95% confidence interval [CI] = 2.61 to 8.71, P < .001) and overall survival (HR = 7.22, 95% CI = 3.46 to 15.06, P < .001). Conclusions: Our study suggests miR-141 is a regulator of brain metastasis from breast cancer and should be examined as a biomarker and potential target to prevent and treat brain metastases.
A study to assess the pharmacokinetics (PK) of a single infusion of cetuximab (IMC-C225)
Authors: E. H. Rubin, J. Doroshow, M. Hidalgo, M. Wojtowicz, L. Leong, R. Donehower, S. Bai, D. Mauro
Journal: Journal of Clinical Oncology (2004)

3084
Vitamin A Intoxication in Adults
Authors: William H. Stimson
Journal: New England Journal of Medicine (1961)

PREVIOUS summaries have considered the symptoms of vitamin A excess in children and adults together. Most of them have been published in pediatric journals. Because of the striking uniformity of the major symptoms in adults it seems worth while to analyze them alone even though only 6 cases have previously been reported. Although the symptoms are quite troubling to the patient they are often so mundane that the physician does not readily pursue them to a diagnosis. It is hoped that with broader awareness the phenomenon may be recognized earlier and its future occurrence prevented. Two distinct types exist, acute . . .
Cytogenetic Analysis of a Gossypol-Induced Murine Myxosarcoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M K Dhaliwal, J O Norman, S Pathak, D L Busbee
Journal: JNCI Journal of the National Cancer Institute (1987)

Cytogenetic analysis of gossypol acetate-induced murine myxosarcoma demonstrated a stemline of 78 chromosomes and the presence of three marker (M) chromosomes produced by robertsonian translocation. Tumor cells at passage 1 that contain chromosomes M1 and M2 were nontumorigenic, whereas cells at passage 3 were tumorigenic in syngeneic mice and showed M1, M2, and M3. The presence of M3 has been implicated to be responsible for the tumorigenic phenotype.
Impaired Forearm Vasodilator Reserve in Patients with Microvascular Angina
Authors: Frederic L. Sax, Richard O. Cannon, Carroll Hanson, Stephen E. Epstein
Journal: New England Journal of Medicine (1987)

In previous work, we described a group of patients with angina-like chest pain and normal coronary arteries. These patients had impaired coronary vasodilator responses to the stress of rapid atrial pacing and to the administration of dipyridamole, a potent vasodilator of coronary arterioles. This abnormality appears to be localized to the prearteriolar microvascular bed. To determine whether these patients have a more generalized abnormality of vasodilator reserve, we used mercury-in-Silastic strain-gauge plethysmography to compare their hyperemic responses to forearm ischemia with those of normal controls. After 10 minutes of ischemia, peak forearm flow was 39.9 +/- 5.0 ml per minute per deciliter in the controls [corrected] and 31.7 +/- 10.5 in the patients [corrected] (21 percent reduction; 95 percent confidence interval, 4 percent to 37 percent). Flow responses were also significantly reduced after three and five minutes of ischemia. Correspondingly, the vascular resistance after ischemia was also consistently higher in the patients with microvascular angina. The degree of vasodilator impairment in the peripheral circulation correlated well with the degree of vasodilator impairment in the coronary circulation (r = 0.74; P less than 0.004). Thus, patients with microvascular angina appear to have an impairment of vasodilator reserve that affects not only their coronary circulation but also their peripheral arterial bed.
The Small Molecule Nobiletin Targets the Molecular Oscillator to Enhance Circadian Rhythms and Protect against Metabolic Syndrome
Authors: Baokun He, Kazunari Nohara, Noheon Park, Yong-Sung Park, Bobby Guillory, Zhaoyang Zhao, Jose M. Garcia, Nobuya Koike, Cheng Chi Lee, Joseph S. Takahashi, Seung-Hee Yoo, Zheng Chen
Journal: Cell Metabolism (2016)