tbuckley/cabot-search huggingface dataset:
PF777 IMMUNOLOGICAL RECONSTITUTION AS A BASIS FOR THE EARLY INITIATION OF PNEUMOCOCCAL VACCINATION AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: I. Stoma, I. Iskrov, V. Smolnikova, I. Lendina, N. Milanovich, A. Uss
Journal: HemaSphere (2019)

Background: In the context of significant advances in the treatment of hematological diseases using the method of autologous hematopoietic stem cell transplantation (auto‐HSCT), the number of patients requiring early vaccination against pneumococcal infection increases worldwide. Current guidelines indicate the early initiation of pneumococcal vaccination starting from 3 months after HSCT. Still, the topical issue is the determination of the earliest optimal dates for the start of vaccination after transplantation, taking into account the dynamics of immunological recovery. Aims: The aim of this study was to determine the optimal timeline for the onset of vaccination with conjugated pneumococcal vaccine in patients with multiple myeloma after auto‐HSCT. Methods: The immune response to the conjugated pneumococcal vaccine is based on the T‐dependent (CD4+) activation of B‐cells, what was taken into account when estimating the timing of immune reconstitution after auto‐HSCT in candidates for vaccination. An immunological study using flow cytometry was performed in 37 adult patients with multiple myeloma prior to the auto‐HSCT procedure, as well as on days +30, +60, +90, +180 after transplantation. Results: After auto‐HSCT, the level of naive B‐cells returns to its original value by the 60th day from transplantation (Kruskal‐Wallis test 41.97; P &lt; 0.001), shown on Fig. 1. At the same time, the level of CD4 + cells did not fall below 200 cells/μl starting from day +30, what indicates the effectiveness of early vaccination with T‐dependent vaccines in this category of patients with immunosuppression. Dendritic cells (DC1 and DC2) are restored in parallel by the 30th day from auto‐HSCT (Kruskal‐Wallis test 25.78; P &lt;0.001 for DC‐1 cells and Kruskal‐Wallis test 11,17; P &lt;0.025, respectively), what confirms the basis for the early vaccination with conjugated pneumococcal vaccines in this category of patients. Summary/Conclusion: The obtained data allows planning the introduction of the first dose of the conjugated pneumococcal vaccine 60 days after autologous HSCT, with the perspective of introducing an individualized vaccination calendar based on immunological parameters. It is also necessary to further implement immunization programs for immunocompromised patients, especially in hematology and cancer setting with the participation of a multidisciplinary team of specialists. image
Structure–activity relationships of inverse agonists for G‐protein‐coupled receptors
Authors: Willem Soudijn, Ineke van Wijngaarden, Adriaan P. Ijzerman
Journal: Medicinal Research Reviews (2005)

Abstract It has been recently established that G‐protein‐coupled receptors (GPCRs) can be constitutively active, i.e., they can be active in the absence of an agonist. This activity can be inhibited by so‐called inverse agonists. For a number of GPCRs, such inverse agonists have been developed and studied, now enabling for the first time a study into their structure–activity relationships. © 2005 Wiley Periodicals, Inc.
Impact of point-of-care testing for respiratory viruses on antibiotic use in adults with exacerbation of airways disease
Authors: Nathan J. Brendish, Samuel Mills, Sean Ewings, Tristan W. Clark
Journal: Journal of Infection (2019)

The ResPOC study demonstrated that syndromic molecular point-of-care testing (POCT) for respiratory viruses was associated with early discontinuation of unnecessary antibiotics compared to routine clinical care. Subgroup analysis suggests these changes occur predominantly in patients with exacerbation of airways disease. Use of molecular POCT for respiratory viruses is becoming widespread but there is a lack of evidence to inform the choice between multiplex syndromic panels versus POCT for influenza only.We evaluated patients from the ResPOC study with exacerbation of asthma or COPD who were treated with antibiotics. The duration of antibiotics and proportion with early discontinuation were compared between patients testing positive and negative for viruses by POCT, and controls. Patients testing positive for viruses by POCT were compared according to virus types.118 patient with exacerbation of airways disease received antibiotics in the POCT group and 111 in the control group. In the POCT group 49/118 (42%) patients tested positive for viruses. Of those testing positive for viruses 17/49 (35%) had early discontinuation of antibiotics versus 9/69 (13%) testing negative and 7/111 (6%) of controls, p<0.0001. Of those positive for viruses by POCT 10/49 (20%) were positive for influenza, 21/49 (43%) for rhinovirus and 18/49 (37%) for other viruses. The proportion with early discontinuation of antibiotics was not different between the virus types (p = 0.34).This data suggests that syndromic molecular POCT for respiratory viruses should be favoured over POCT for influenza alone in adults with exacerbation of airways disease.
AB0826 OSTEODENSITOMETRIC PROFILE DURING JUVENILE CELIAC DISEASE
Authors: Cyrine Daldoul, Nejla El Amri, Sadok Laataoui, Khadija Baccouch, Hela Zeglaoui, Elyes Bouajina
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Bone mineralization abnormalities are often seen in children with chronic gastrointestinal disease. Among these pathologies, celiac disease (CD) is the most likely source of abnormalities of bone mineral density. These disorders are of multifactorial origin involving malabsorption, nutritional status, decreased physical activity and chronic inflammation. <h3>Objectives</h3> The purpose of this study was to determine the frequency and factors associated with lower bone mineral density in children with CD. <h3>Methods</h3> This is a retrospective study, over a period of 4 years (from January 2014 to December 2017) including children followed for CD who had a measurement of bone mineral density (BMD) by DEXA. Clinical, anthropometric and densitometry data (BMD at the femoral and vertebral site) were recorded. <h3>Results</h3> Thirty-six children were collected. Among them 29 were girls and 7 were boys. The average age was 11.94 years old. The average size was 137.8 cm. The average weight was 35.3 kg. The average body mass index (BMI) was 17.69 kg/m<sup>2</sup> [13.05-21.69 kg/m<sup>2</sup>]. The average vertebral BMD was 0.891 g/cm3. The average z-score was -1.08. BMD was normal in 26 cases. A decrease in bone mineral density with respect to chronological age was observed in 10 cases. A very significant correlation was observed between BMI and vertebral BMD (r = 0.75, p = 0.000). <h3>Conclusion</h3> The frequency and severity of the decline in BMD in children with CD requires regular monitoring. It seems to be favored by a low BMI, which is common during CD in relation with the associated malabsorption. <h3>Disclosure of Interests</h3> None declared
Doxebo (doxorubicin-free Doxil-like liposomes) is safe to use as a pre-treatment to prevent infusion reactions to PEGylated nanodrugs
Authors: Yaelle Bavli, Ilan Winkler, Bing Mae Chen, Steve Roffler, Rivka Cohen, Janos Szebeni, Yechezkel Barenholz
Journal: Journal of Controlled Release (2019)
The Role of Senescence in the Development of Nonalcoholic Fatty Liver Disease and Progression to Nonalcoholic Steatohepatitis
Authors: Alkistis‐Maria Papatheodoridi, Lampros Chrysavgis, Michael Koutsilieris, Antonios Chatzigeorgiou
Journal: Hepatology (2019)

In recent years, cellular senescence has generated a lot of interest among researchers because of its involvement in both the normal aging process and common human diseases. During senescence, cells undergo alterations that include telomere shortening, nuclear area enlargement, and genomic and mitochondrial DNA damage, leading to irreversible cell cycle arrest, and secretion of proinflammatory cytokines. Evidence suggests that the complex process of senescence is involved in the development of a plethora of chronic diseases including metabolic and inflammatory disorders and tumorigenesis. Recently, several human and animal studies have emphasized the involvement of senescence in the pathogenesis and development of liver steatosis including the progression to nonalcoholic steatohepatitis (NASH) as characterized by the additional emergence of inflammation, hepatocyte ballooning, and liver fibrosis. The development of nonalcoholic fatty liver disease (NAFLD) and its progression to NASH are commonly accompanied by several pathophysiological events including metabolic dysregulation and inflammatory phenomena occurring within the liver that may contribute to or derive from cellular senescence, implying that the latter may be both a stimulus and a consequence of the disease. Conclusion: In this review, we summarize the current literature on the impact of cellular senescence in NAFLD/NASH and discuss the effectiveness and safety of novel senolytic drugs and therapeutic options available to delay or treat the disease. Finally, we identify the open questions and issues to be addressed in the near future.
PB1909 HYPOGAMMAGLOBULINEMIA AS A PREDICTOR OF SURVIVAL IN OLDER PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: E. Umit, M. Baysal, V. Bas, S. Gulsaran, U. Demirci, O. Kirkizlar, A.M. Demir
Journal: HemaSphere (2019)

Background: chronic lymphocytic leukemia (CLL) is the most frequent leukemia of adults and has a median age of 71 years at diagnosis. Approach to CLL patients may include watchful waiting as well as chemotherapy and recently, immunotherapy and small molecules. As life expectancy in general population increases, a significant increase in patients who are accepted as old is also expected. As fitness is not a simple concept, explained with chronological age alone, older patients are suggested to be assessed individually and thoroughly in terms of cognition, comorbidity and mental health. Aims: We aimed to investigate the factors which may be related with survival and should be improved in older patients with CLL. Methods: 104 patients who were 65 years and older diagnosed and treated for CLL were enrolled in the study in a retrospective manner. Demographic and survival data were recorded from files. Results: Mean age of our patients was 76,69 years (65‐91). 45 patients were female (43,3%) while 59 were male (56,7%). Median duration of watchful waiting period was 18 months (0‐74). 13 patients were Rai Stage 0 (12,5%) while 36 were Stage I (34,6%), 40 were Stage II (38,5%), 5 were Stage III (4,8%) and 10 were Stage IV (9,6%). Median lymphocyte count was 19.750/μL, median hemoglobin level 12,7 g/dL and median platelet count was 193 x10 6 /L. Median survival was 46 months (2‐86 months). 40 patients had hypogammaglobulinemia (38,5%). 23 patients have developed a secondary malignancy (22,1%). 40 patients had immune thrombocytopenia (ITP) (38,5%) and 5 patients had autoimmune hemolytic anemia (AHA)(4,8%). Regarding the relation of complications during the course of disease, only hypogammaglobulinemia was observed to be related with survival. In patients who had hypogammaglobulinemia, mean survival was 42,25 months while in patients who did not have hypogammaglobulinemia, mean survival was 61,3 months (p &lt; 0,05). Summary/Conclusion: Hypogammaglobulinemia should be sought in every older CLL patient and be supported if found. Survival of patients who have hypogammaglobulinemia is shorter, which may be explained with increased rates of infections as well as secondary malignancies due to the immune compromisation status.
AB0804 OSTEOARTHRITIS (OA) PATIENTS WITH LOW BASELINE MULTIDIMENSIONAL HEALTH ASSESSMENT QUESTIONNAIRE/ROUTINE ASSESSMENT OF PATIENT INDEX DATA (MDHAQ/RAPID3) SCORES FOR PAIN, PATIENT GLOBAL ASSESSMENT AND MORNING STIFFNESS ARE SIGNIFICANTLY MORE LIKELY TO IMPROVE OVER THE NEXT 6 MONTHS
Authors: Isabel Castrejon, Mariam Riad, Joel Block, Theodore Pincus
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The course of osteoarthritis (OA) is highly variable; up to 50% of patients show little progression over many years, while other patients show rapid progression. Relatively little is known about the clinical variables that might affect prognosis for progression. <h3>Objectives</h3> To analyze OA patient status in routine care at baseline according to baseline candidate prognostic multidimensional health assessment questionnaire (MDHAQ) variables, and 6 months later as improved, worsened or similar according to the same variables. <h3>Methods</h3> All patients complete an MDHAQ/RAPID3 (routine assessment of patient index data) at all visits prior to seeing the rheumatologist at an academic site. The 2-page MDHAQ/RAPID3 includes 0-10 scores for physical function (FN), and visual analog scales (VAS) for pain (PN) and patient global assessment (PATGL), compiled into a 0-30 RAPID3, as well as a 0-10 fatigue VAS, 0-48 self-report painful joint count, 0-60 symptom checklist, and minutes of morning stiffness. OA patients were classified into 3 groups, based on change in RAPID3 ≥3.8, the minimal clinically important improvement (MCII), from baseline to 6-month follow-up (range 3-9 months), as &gt;3.8, &lt;3.8, or within 3.8 units. Statistical significance was studied with one-way analysis of variance (ANOVA) and chi square. <h3>Results</h3> Among 173 OA patients, 22 (13%) were improved, 95 (55%) unchanged, and 56 (32%) worsened 6 months later. The 3 groups did not differ significantly in age, gender, ethnicity, educational level or BMI (Table). Patients who improved compared to those who were unchanged or worsened had significantly lower baseline RAPID3, pain and patient global VAS, and morning stiffness. The patients who improved also had lower, but not statistically significant, physical function score and fatigue VAS. No differences were seen among the 3 groups in numbers of symptoms or self-report painful joint counts (Table). <h3>Conclusion</h3> OA patients who were improved over 6 months according to RAPID3 had significantly lower baseline scores for RAPID3, pain, patient global assessment, and morning stiffness. It may be of value to stratify patients in clinical trials, other clinical research, and routine clinical care according to these variables. <h3>Disclosure of Interests</h3> None declared
PS1157 EFFECT OF DOSE MODIFICATIONS ON RESPONSE TO DUVELISIB IN PATIENTS WITH RELAPSED/REFRACTORY CLL/SLL IN THE DUO TRIAL
Authors: P. Ghia, I. Flinn, N. Lamanna, M. Montillo, Á. Illés, G. Etienne, J. Delgado, B. Kuss, C. Tam, F. Offner, F. Bosch, M. Davids, U. Jäger, F. Cymbalista, D. Weaver, S. Lustgarten, H. Youssoufian, S. Stilgenbauer
Journal: HemaSphere (2019)

Background: Duvelisib (DUV), a first‐in‐class oral dual PI3K‐δ,γ inhibitor, is approved for treatment of relapsed/refractory (R/R) CLL/SLL after ≥ 2 prior therapies. In the phase 3 DUO trial, DUV 25 mg BID significantly improved efficacy vs ofatumumab (OFA; mPFS, 13.3 vs 9.9 mo; HR, 0.52 [ P &lt; .0001]; ORR, 74% vs 45% [ P &lt; .0001]) in pts with R/R CLL/SLL (Flinn et al. Blood 2018). Treatment‐emergent AEs (TEAEs) of special interest (AESIs) such as infections, diarrhea, colitis, neutropenia, rash, ALT/AST elevation, and pneumonitis, were moderate and manageable with early intervention and dose modification. Aims: To examine dose‐modification patterns and their impact on response to DUV in the DUO trial. Methods: TEAEs were assessed according to the NCI CTCAE v4.03. Dose interruptions (DI) or reductions (DR) to 15, 10, or 5 mg BID were permitted per study protocol to manage TEAEs. Responses were assessed by an independent review committee before and after dose modifications and were analyzed using descriptive statistics. Results: Among 158 DUV‐treated pts, median duration of DUV exposure was 11.6 mo (vs 5.3 mo, OFA). DI and DR occurred in 80% (126/158) and 27% (43/158) of pts, respectively. The most common cause of DI was diarrhea (23%), followed by neutropenia (12%) and pneumonia or colitis (11% each). Among responders (n = 118), median time to first response on DUV was 1.9 mo and estimated median duration of response was 11.1 mo. Median time to first DI was 3.9 mo and median duration of DI was 15 d (range, 1–133 d). Response to DUV was improved or maintained in most pts evaluated for response who had ≥ 1 DI for &gt; 1 wk (84% [42/50]) or &gt; 2 wk (82% [31/38]) followed by ≥ 3 wk on DUV. In a landmark analysis, median PFS was similar in pts with DI and those without DI for &gt; 1 wk (17.8 vs 16.3 mo) or &gt; 2 wk (17.8 vs 16.3 mo) within the first 3 mo. The median time to DR after CR/PR was 5.6 mo (n = 25) and median duration was 3.4 mo. Median time to onset across AESIs after starting DUV ranged from 2.2 to 4.3 mo; median time to resolution was within 4 wk across AESIs. Proportions of pts experiencing AESIs were stable or decreased over time after 3–6 mo: 0–3 mo, 64% (101/158); &gt; 3–6 mo, 63% (86/137); &gt; 6–9 mo, 47% (54/114); &gt; 9–12 mo, 52% (52/100), and seldom led to discontinuation of DUV (≤ 10%). Summary/Conclusion: DI/DR can contribute to the effective management of TEAEs with DUV. These findings suggest that DI of &gt; 1–2 weeks or more do not appear to significantly impact response to DUV or PFS.
AB0933 ANALYSIS OF THE STATE OF IMMUNITY IN PATIENTS WITH JIA IN TREATMENT
Authors: Inmaculada Concepcion Aranda-Valera, Ladehesa Pineda Lourdes, Font Ugalde Pilar, Fernández de la Puebla Lechuga Elena, Copete Marín Sara, Eduardo Collantes Estevez, Roldán Molina Rosa
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The correct indication of the suspension of treatment with FAMES and biological therapy in pediatric patients, in the presence of a mild infectious disease or vaccination is a common problem in children's rheumatology. In patients with juvenile idiopathic arthritis (JIA), joint or extra-articular clinical reactivation during these "pauses" is not uncommon, however, there are not enough studies in the pediatric population to show the influence of treatments on the immune system., and therefore, that justify this clinical practice. <h3>Objectives</h3> To analyze the levels of T, B and NK lymphocyte subpopulations in patients diagnosed with JIA treated with FAMES and biological therapy. <h3>Methods</h3> A descriptive and cross-sectional study in which 39 patients from the Pediatric Rheumatology Unit of the Reina Sofía University Hospital were recruited, diagnosed with JIA according to the ILAR 2001 criteria. The patients were divided into four groups: 8 controls in clinical remission without treatment, 17 in treatment with DMARD in monotherapy, 7 in biological treatment in monotherapy and 7 in treatment with DMARD-biological. Patients with systemic JIA were excluded because they had a pathogenic mechanism different from the rest of the JIA categories. By flow cytometry, the levels of CD3, CD4, CD8 and CD19 cells were measured for acquired immunity and from NK for innate, the CD4/CD8 index was also calculated. <h3>Results</h3> The mean age of the 39 patients was 10 ± 5.7 years, 29 were girls (74.3%), 4 patients had arthritis related to enthesitis, 16 patients had oligoarticular involvement ANA +, 6 subjects polyarticular involvement FR- and 13 they were psoriatic arthritis. Although no statistically significant differences were found when contracting cellular levels among the 4 groups evaluated, it was observed that the group treated with DMARD monotherapy had the highest percentage of children with alterations in cellular levels CD3, CD4, CD8 and CD19 (41.17% of the patients of the group); the group treated in monotherapy with biological treatment (28%) presented alteration in the levels of CD8 and CD19 and the group treated in combination of DMARD and biological (14.28%) in CD19. On the other hand, the NK cells and the CD4/CD8 index were not altered in any of the groups. Only 6 cases of serious infections were registered in patients in combination therapy (DMARD-biologic) who had received corticosteroids by clinical activity. There were no statistical differences between patients who had received corticosteroids and those who did not. <h3>Conclusion</h3> Patients in treatment with DMARD monotherapy had a tendency to decrease cellular levels. On the other hand, alterations in innate immunity or CD4/CD8 index were not observed. <h3>Disclosure of Interests</h3> None declared
Abstract 19221: Inter Shock Changes of the Ventricular Fibrillation Waveform in Relation to Return of Spontaneous Circulation: Amplitude or Frequency Driven?
Authors: Jos Thannhauser, Joris Nas, Judith L Bonnes, Gjerrit Meinsma, Pierre M van Grunsven, Joep L Smeets, Menko J de Boer, Marc A Brouwer
Journal: Circulation (2016)

Introduction: Recent studies on ventricular fibrillation (VF) waveform characteristics described that an increasing amplitude spectrum area (AMSA) is associated with return of spontaneous circulati...
Randomized phase II study of recombinant human endostatin in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer (NCT00912392).
Authors: Shun Lu, Lu Li, Yi Luo, Li Zhang, Zhiwei Chen, Wu Gang, Ping Chen, Cheng Huang, Shuliang Guo, Yiping Zhang, Xiangqun Song, Meijun Lv, Wei Li, Chunhong Hu, Cheng-ping Hu
Journal: Journal of Clinical Oncology (2012)

7091 Background: Endostar (recombinant human endostatin) is a novel antiangiogenesis drug developed in China for non-small cell lung cancer (NSCLC). Because of promising efficacy signals, we performed a randomized phase II trial to assess the efficacy and safety of adding endostar to first-line standard chemotherapy for treatment of chemonaive extensive-stage small-cell lung cancer (SCLC). Methods: Extensive-stage SCLC patients with a performance status 0-2 were randomly assigned to endostar group (endostar 7.5mg/m 2 D1-D14 with carboplatin AUC=5 plus etoposide 60mg/m 2 D1-D5 of a 21-day cycle for six cycles) or the control group (the same dose of carboplatin plus etoposide). Patients in endostar treatment group with CR, PR and SD were treated with single-agent endostar until progression or unacceptable toxicity. The primary end point is progression-free survival (PFS). The secondary end points are overall survival (OS) and response rate (RR). Results: 140 patients were enrolled from June 2009 to June 2011, and 137 patients were included in full analysis set. 68 patients were randomly assigned to the endostar treatment and 69 patients to the control group. Median age was 57 years and 80.9% for male in the endostar group while median age was 58 years and 85.5% for male in the control group. Median PFS was similar for endostar and control group (6.2 v 5.9 months, P=0.163, HR 0.762; 95%CI 0.519-1.119). Median overall survival (OS) was also similar for both groups (12.4 v 12.3 months, P=0.475, HR 0.835; 95%CI 0.508-1.371). Overall RR were 76.5% for endostar group and 68.1% for the control group (p=0.275). 20 patients in the endostar group completed six cycles of therapy and subsequently treated with single-agent endostar as maintenance therapy and the median PFS and OS were 6.8 and 12.4 months respectively. The rate of ≥ 3 grade adverse events occurred in both groups was similar and no new or unexpected safety signals for endostar were observed. Conclusions: The addition of endostar to carboplatin plus etoposide for treatment of extensive stage SCLC didn’t improve the PFS significantly, with an acceptable toxicity profile. And no improvement in OS was observed.
Rammya Mathew: Infant feeding, informed choice, and shared decisions
Authors: Rammya Mathew
Journal: BMJ (2019)

Earlier this year Channel 4’s Dispatches shone a light on misleading marketing practices used by multinational companies to promote infant formula.1 That same week The BMJ went public with its decision to stop accepting advertising for infant formula.2 Its announcement received a mixed reception on social media and reignited discussions among the public and medical professionals around infant feeding.

Both as a GP and as a mother, I want to see more being done to promote shared decision making around infant feeding. There’s a strong public health imperative to improve breastfeeding rates, but as …