bluuebunny/crossref_metadata_2025 huggingface dataset:
Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial
Authors: Gullo Giuseppe , Eustace Alex J. , Canonici Alexandra , Collins Denis M. , Kennedy Michael J. , Grogan Liam , Breathhnach Oscar , McCaffrey John , Keane Maccon , Martin Michael J. , Gupta Rajnish , Leonard Gregory , O’Connor Miriam , Calvert Paula M. , Donnellan Paul , Walshe Janice , McDermott Enda , Scott Kathleen , Hernando Andres , Parker Imelda , Murray David W. , O’Farrell Alice C. , Maratha Ashwini , Dicker Patrick , Rafferty Mairin , Murphy Verena , O’Donovan Norma , Gallagher William M. , Ky Bonnie , Tryfonopoulos Dimitrios , Moulton Brian , Byrne Annette T. , Crown John
Published: July 2019

Background:

Combining bevacizumab and chemotherapy produced superior response rates compared with chemotherapy alone in metastatic breast cancer. As bevacizumab may cause hypertension (HTN) and increase the risk of cardiac failure, we performed a pilot study to evaluate the feasibility and toxicity of a non-anthracycline-containing combination of docetaxel with cyclophosphamide and bevacizumab in early stage breast cancer patients.

Methods:

Treatment consisted of four 3-weekly cycles of docetaxel and cyclophosphamide (75/600 mg/m2). Bevacizumab was administered 15 mg/kg intravenously on day 1, and then every 3 weeks to a total of 18 cycles of treatment. Serum biomarker concentrations of vascular endothelial growth factor (VEGF), cardiac troponin-I (cTnI), myeloperoxidase (MPO), and placental growth factor (PlGF) were quantified using enzyme-linked immunosorbent assay (ELISA) in 62 patients at baseline and whilst on treatment to determine their utility as biomarkers of cardiotoxicity, indicated by left ventricular ejection fraction (LVEF).

Results:

A total of 106 patients were accrued in nine sites. Median follow up was 65 months (1–72 months). Seventeen protocol-defined relapse events were observed, accounting for an overall disease-free survival (DFS) rate of 84%. The DFS rates for hormone receptor positive (HR+) and triple-negative (TN) patients were 95% versus 43%, respectively. The median time to relapse was 25 (12–54) months in TN patients versus 38 (22–71) months in HR+ patients. There have been 13 deaths related to breast cancer . The overall survival (OS) rate was 88%. The 5-year OS rate in HR+ versus TN was 95% versus 57%. None of the measured biomarkers predicted the development of cardiotoxicity.

Conclusions:

We observed a low relapse rate in node-positive, HR+ patients; however, results in TN breast cancer were less encouraging. Given the negative results of three large phase III trials, it is unlikely that this approach will be investigated further.

Trial Registration

ClinicalTrials.gov Identifier: NCT00911716.
Learnings From SAAHAS—A Queer Affirmative CBT-Based Group Therapy Intervention for LGBTQIA+ Individuals in Mumbai, India
Authors: Wandrekar Jagruti , Nigudkar Advaita
Published: July 2019

Background: There are few published research studies documenting intervention modalities used with LGBTQIA+ individuals in India. This is a pilot study documenting possibly the first of its kind therapy group named SAAHAS based in Mumbai.

Methodology: SAAHAS was a free, open group for therapy meant for queer individuals. The therapeutic approach used was queer affirmative cognitive behavior therapy. Facilitators were queer psychologists. A survey was conducted to assess the needs of potential participants. Recruitment protocol, group, and session formats and structures are described here. Evaluation was primarily through anonymous participant feedback.

Results: A total of 71 participants completed the intake survey, 28 participants attended at least one group session, and 78% of these were cis-gay men, with low representation of lesbian, bisexual women and transgender and gender nonconforming individuals. Over one year, 12 monthly sessions were conducted. Feedback suggested that the participants liked the group, found it to be a safe space, and reported an improvement in mental health, reduction of distress, reduction of feelings of isolation, and acquisition of knowledge and skills to tackle problems faced by queer people. Peer support, safe space, expert-cum-peer facilitator stance, and queer affirmative cognitive behavior therapy-based therapeutic approach may have contributed to group efficacy.

Conclusion: The SAAHAS therapy group experience provides a useful low-cost therapeutic framework for queer individuals in India.
Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial
Authors: Muss Hyman B. , Polley Mei-Yin C. , Berry Donald A. , Liu Heshan , Cirrincione Constance T. , Theodoulou Maria , Mauer Ann M. , Kornblith Alice B. , Partridge Ann H. , Dressler Lynn G. , Cohen Harvey J. , Kartcheske Patricia A. , Perez Edith A. , Wolff Antonio C. , Gralow Julie R. , Burstein Harold J. , Mahmood Ahmad A. , Sutton Linda M. , Magrinat Gustav , Parker Barbara A. , Hart Ronald D. , Grenier Debjani , Hurria Arti , Jatoi Aminah , Norton Larry , Hudis Clifford A. , Winer Eric P. , Carey Lisa
Published: July 2019

PURPOSE

Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years.

PATIENTS AND METHODS

Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician’s choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS.

RESULTS

The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer–specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor–negative patients (HR, 0.66; P = .02), but not among hormone receptor–positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients.

CONCLUSION

With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease. Competing risks in this older population dilute overall survival benefits.
Preemptive and Preventive Pain Psychoeducation and Its Potential Application as a Multimodal Perioperative Pain Control Option: A Systematic Review
Authors: Horn Audrey , Kaneshiro Kelly , Tsui Ban C. H.
Published: July 2019

The common treatment for postoperative pain is prescription opioids. Yet, these drugs have limited effect in preventing chronic pain from surgical intervention and have in part contributed to the opioid epidemic. Recently, preemptive analgesia and multimodal analgesia have been proposed with widely gained acceptance in addressing the pain issues. However, both analgesic approaches have been focused on pharmacological means while completely neglecting the psychological aspect. To address this epidemic, we have conducted a systematic review of preoperative educational methods to explore its application as both a preemptive and a preventive psychological approach to decrease postsurgical pain and improve outcome. Preemptive psychoeducation occurs before surgery and would include information about regional or neuraxial analgesia, while preventive psychoeducation occurs throughout the perioperative period. The content and presentation of preemptive psychoeducation can help patients form accurate expectations and address their concerns of surgical outcome, leading to a significant decrease in patients’ anxiety levels. By addressing the psychological needs of patients through preoperative education, one can decrease postoperative recovery time and postsurgical acute pain. Reduced postsurgical acute pain results in fewer opioid prescriptions, which theoretically lowers the patient’s risk of developing chronic postsurgical pain (CPSP), and potentially offers a novel concept using preemptive pain psychoeducation as a part of multimodal pain management solution to the opioid epidemic.
Update on Congenital Diaphragmatic Hernia
Authors: Chatterjee Debnath , Ing Richard J. , Gien Jason
Published: July 2019

Congenital diaphragmatic hernia (CDH) is a rare developmental defect of the diaphragm, characterized by herniation of abdominal contents into the chest that results in varying degrees of pulmonary hypoplasia and pulmonary hypertension (PH). Significant advances in the prenatal diagnosis and identification of prognostic factors have resulted in the continued refinement of the approach to fetal therapies for CDH. Postnatally, protocolized approaches to lung-protective ventilation, nutrition, prevention of infection, and early aggressive management of PH have led to improved outcomes in infants with CDH. Advances in our understanding of the associated left ventricular (LV) hypoplasia and myocardial dysfunction in infants with severe CDH have allowed for the optimization of hemodynamics and management of PH. This article provides a comprehensive review of CDH for the anesthesiologist, focusing on the complex pathophysiology, advances in prenatal diagnosis, fetal interventions, and optimal postnatal management of CDH.
Ketamine Administration During Hospitalization Is Not Associated With Posttraumatic Stress Disorder Outcomes in Military Combat Casualties: A Matched Cohort Study
Authors: Highland Krista B. , Soumoff Alyssa A. , Spinks Elizabeth A. , Kemezis Patricia A. , Buckenmaier Chester C.
Published: July 2019

BACKGROUND:

Ketamine is routinely used within the context of combat casualty care. Despite early concerns that ketamine administration may be associated with elevated risk of posttraumatic stress disorder (PTSD), more recent evidence suggests no relationship. Because PTSD occurs with regular frequency in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Service Members (SMs) and combat-related injuries are associated with higher likelihood of PTSD, it is important to investigate the relationship between ketamine exposure during inpatient medical and surgical care and PTSD symptoms in OIF/OEF SMs.

METHODS:

Medical record data from OIF/OEF SMs medically evacuated from combat (N = 1158) included demographic characteristics, injury severity, body areas injured, and PTSD Checklist (PCL) scores. The primary analysis assessed the association between ketamine versus nonketamine exposure on positive PTSD screen (logistic regression) and PCL scores (linear regression) after using 1:1 propensity score matching to adjust for available potential confounding variables. Because there were 2 primary outcomes, the binary positive PTSD screen (yes/no) and continuous PCL score, the significance level was set at P ≤ .025. In sensitivity analyses, propensity scores were used to match ketamine to nonketamine records in a 1:4 ratio, as well as to conduct inverse probability treatment weighting (IPTW). Regressions examining the relationship between ketamine exposure and outcomes were repeated for unconditional, 1:4 matching, and IPTW models.

RESULTS:

In the sample, 107 received ketamine and 1051 did not. In the logistic regression, the probability of a positive PTSD screen was not significantly different between ketamine versus nonketamine patients (odds ratio [OR] = 1.28; 95% confidence interval [CI], 0.48–3.47; P = .62). In the linear regression, PCL scores were not significantly different between ketamine versus nonketamine patients (mean difference = 1.98 [95% CI, −0.99 to 4.96]; P = .19). The results were consistent in the unconditional, 1:4 matching, and IPTW models.

CONCLUSIONS:

No differences in PTSD screening risk or symptom levels between ketamine exposed and nonexposed were found. Given the small sample size, wide CIs of the effects, and additional confounds inherent to retrospective studies, future studies are needed to examine the complex relationships between ketamine and psychological symptoms.
Delaying Elective Surgery in Geriatric Patients: An Opportunity for Preoperative Optimization
Authors: Wong Serena P. , Zietlow Kahli M. , McDonald Shelley R. , Barbeito Atilio , Colon-Emeric Cathleen S. , Lagoo-Deenadayalan Sandhya A. , Loyack Nancy , Heflin Mitchell T.
Published: July 2019

Deciding whether to pursue elective surgery is a complex process for older adults. Comprehensive geriatric assessment (CGA) can help refine estimates of benefits and risks, at times leading to a delay of surgery to optimize surgical readiness. We describe a cohort of geriatric patients who were evaluated in anticipation of elective abdominal surgery and whose procedures were delayed for any reason. Themes behind the reasons for delay are described, and a holistic framework to guide preoperative discussion is suggested.
Major Neurologic Complications Associated With Postdural Puncture Headache in Obstetrics: A Retrospective Cohort Study
Authors: Guglielminotti Jean , Landau Ruth , Li Guohua
Published: July 2019

BACKGROUND:

Increased risks of cerebral venous thrombosis or subdural hematoma, bacterial meningitis, persistent headache, and persistent low back pain are suggested in obstetric patients with postdural puncture headache (PDPH). Acute postpartum pain such as PDPH may also lead to postpartum depression. This study tested the hypothesis that PDPH in obstetric patients is associated with significantly increased postpartum risks of major neurologic and other maternal complications.

METHODS:

This retrospective cohort study consisted of 1,003,803 women who received neuraxial anesthesia for childbirth in New York State hospitals between January 2005 and September 2014. The primary outcome was the composite of cerebral venous thrombosis and subdural hematoma. The 4 secondary outcomes were bacterial meningitis, depression, headache, and low back pain. PDPH and complications were identified during the delivery hospitalization and up to 1 year postdelivery. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using the inverse probability of treatment weighting approach.

RESULTS:

Of the women studied, 4808 (0.48%; 95% CI, 0.47–0.49) developed PDPH, including 264 cases (5.2%) identified during a readmission with a median time to readmission of 4 days. The incidence of cerebral venous thrombosis and subdural hematoma was significantly higher in women with PDPH than in women without PDPH (3.12 per 1000 neuraxial or 1:320 vs 0.16 per 1000 or 1:6250, respectively; P < .001). The incidence of the 4 secondary outcomes was also significantly higher in women with PDPH than in women without PDPH. The aORs associated with PDPH were 19.0 (95% CI, 11.2–32.1) for the composite of cerebral venous thrombosis and subdural hematoma, 39.7 (95% CI, 13.6–115.5) for bacterial meningitis, 1.9 (95% CI, 1.4–2.6) for depression, 7.7 (95% CI, 6.5–9.0) for headache, and 4.6 (95% CI, 3.3–6.3) for low back pain. Seventy percent of cerebral venous thrombosis and subdural hematoma were identified during a readmission with a median time to readmission of 5 days.

CONCLUSIONS:

PDPH is associated with substantially increased postpartum risks of major neurologic and other maternal complications, underscoring the importance of early recognition and treatment of anesthesia-related complications in obstetrics.
A Case Report of Surgical Entrapment and Catheter Embolization: A Rare Complication of Peripherally Inserted Central Catheters
Authors: More Shikhar , Mishra Seema , Garg Vishnu Kumar , Chandrashekhara S. H. , Bharti Sachidanand Jee
Published: July 2019

Peripherally inserted central catheters (PICCs) are a feasible alternative to conventional central venous access. PICCs are often used perioperatively for central venous pressure monitoring and administration of vasoactive drugs especially in cancer patients. Catheter breakage and embolization are rare but potentially fatal complications, and most of the reported literature pertains to pediatric patients after medium- to long-term use. In this report, we describe a rare scenario of catheter breakage, entrapment, and embolization in a patient caused by inadvertent surgical clip and suture placement.
Talking About Nothing
Authors: Vecsey Zoltán
Published: July 2019

Some singular terms are referentially empty by necessity. Oliver and Smiley have recently introduced the term ‘zilch’ for illustrating this kind of emptiness. The emptiness of ‘zilch’ is supposed to arise from the fact that its extension has been defined by a logically unsatisfiable condition. Casati and Fujikawa disagree with this explanation and claim that ‘zilch’ refers to some null thing. In this paper, I argue that neither of these positions is correct, since, for different reasons, they both misinterpret the phenomenon of referential emptiness. As an alternative, I propose a representationalist account of emptiness, which can explain the properties of ‘zilch’ and similar terms more effectively.
Beall-ing O
Authors: Joaquin Jeremiah Joven
Published: July 2019

In “A neglected reply to Prior’s dilemma” Beall [2012] presents a Weak Kleene framework where Prior’s dilemma for Hume’s no-ought-fromis thesis fails. It fails in the framework because addition, the inference rule that one of its horns relies on, is invalid. In this paper, we show that a more general result is necessary for the viability of Beall’s proposal –  a result, which implies that Hume’s thesis holds in the proposed framework. We prove this result and thus show that Beall’s proposal is indeed viable.
The Nature of Scientific Philosophy
Authors: Shramko Yaroslav
Published: July 2019

The goal of this paper is to explain the nature of philosophy as a distinct science with its own subject-matter. This is achieved through a comparative analysis of mathematical and philosophical knowledge that reveals a profound similarity between mathematics and philosophy as mutually complementary sciences exploring the field of abstract entities that can be comprehended only by purely a priori theoretical inquiry. By considering this complementarity, a general definition of philosophy can be obtained by dualizing the traditional Aristotelian definition of mathematics as the “science of quantity”. Philosophy should thus be interpreted as an a priori science of the pure qualitative attributes of being.
Explicit Conditionals in the Framework of Classical Conditional Logic
Authors: Pizzi Claudio E. A.
Published: July 2019

The paper proposes a first approach to systems whose language includes two primitives (>+ and >-) as symbols for factual and counterfactual conditionals which are explicit, i.e. that are stated jointly with the truth or falsity of the antecedent clause. In systems based on this language, here called 2-conditional, the standard corner operator may be defined by (Def>) A > B := (A >+ B)∨(A >- B), while in classical conditional systems one could introduce the two symbols for explicit conditionals by the definitions (Def>+) A >+ B := A∧(A>B) and (Def>-) A>- B := ¬A∧(A>B). Two 2-conditional systems, V² and VW², are axiomatized and proved to be definitionally equivalent to the monoconditional systems V and VW. A third system VWTr² is characterized by an axiom stating the transitivity of factual conditionals and is shown to be distinct from V², from VW² and from the 2-conditional version of Lewis’ well-known system VC, here named VC². The same may be said for a fourth system VW²◊ ±, based on an axiom inderivable in VC²: ◊(A >+ B) ⊃ ◊( ¬A >- ¬B). VC² contains what is here called a “semi-collapse” of the operator >+ and it is argued that it is inadequate as a logic for both factual and counterfactual conditionals. The last section shows that several different definitions of the corner operators in terms of >+ and >- may be introduced as an alternative to (Def>).
On a multilattice analogue of a hypersequent S5 calculus
Authors: Grigoriev Oleg , Petrukhin Yaroslav
Published: July 2019

In this paper, we present a logic MMLS5n which is a combination of multilattice logic and modal logic S5. MMLS5n is an extension of Kamide and Shramko’s modal multilattice logic which is a multilattice analogue of S4. We present a cut-free hypersequent calculus for MMLS5n in the spirit of Restall’s one for S5 and develop a Kripke semantics for MMLS5n, following Kamide and Shramko’s approach. Moreover, we prove theorems for embedding MMLS5n into S5 and vice versa. As a result, we obtain completeness, cut elimination, decidability, and interpolation theorems for MMLS5n. Besides, we show the duality principle for MMLS5n. Additionally, we introduce a modification of Kamide and Shramko’s sequent calculus for their multilattice version of S4 which (in contrast to Kamide and Shramko’s original one) proves the interdefinability of necessity and possibility operators. Last, but not least, we present Hilbert-style calculi for all the logics in question as well as for a larger class of modal multilattice logics.
Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19
Authors: Xie Xiaoyan , Liu Miao , Meng Qiang
Published: July 2019

Objectives

Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation.

Methods

MSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, in vivo experimentation explored bone mineral density, bone mineral content, and the ash weight and dry weight of femoral bone.

Results

The results revealed that AP significantly promoted cell viability, upregulated cyclin D1 and increased RUNX2, OCN, ALP, and BMP-2 protein levels in MSCs. Moreover, we found that AP notably activated PI3K/AKT and Wnt/β-catenin signalling pathways in MSCs. Additionally, the relative expression level of H19 was upregulated by AP in a dose-dependent manner. The promoting effects of AP on cell proliferation and osteoblast differentiation were reversed by H19 knockdown. Moreover, in vivo experimentation further confirmed the promoting effect of AP on bone formation.

Conclusion

These data indicate that AP could promote MSC proliferation and osteoblast differentiation by regulating H19. Cite this article: X. Xie, M. Liu, Q. Meng. Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone Joint Res 2019;8:323–332. DOI: 10.1302/2046-3758.87.BJR-2018-0223.R2.
Yersinia enterocolitica: Prevalence, virulence, and antimicrobial resistance from retail and processed meat in Egypt
Authors: Younis Gamal , Mady Mona , Awad Amal
Published: July 2019

Aim: The objectives of this study were to investigate the prevalence of Yersinia enterocolitica in retail chicken meat, ground and processed beef meat, determine their virulence-associated genes, antimicrobial susceptibility pattern, molecular detection of extended-spectrum β-lactamases, and their capability of biofilm formation in vitro. Materials and Methods: A total of 210 samples (120 retail chicken meat, 30 ground beef, 30 beef burger, and 30 sausage samples) were collected from different retail chicken outlets and markets located at Mansoura city between December 2016 and April 2017. Meat samples were examined bacteriologically for the existence of Y. enterocolitica; bacterial colonies that displayed positive biochemical properties were subjected to polymerase chain reaction targeting 16 rRNA gene. Y. enterocolitica isolates were tested for their susceptibility to six antimicrobial agents using disk diffusion method. Uniplex PCR was used for screening Y. enterocolitica isolates for the presence of two virulence chromosome-associated genes (ail and yst), and β-lactamases (blaTEM and blaSHV). The capability of Y. enterocolitica to form biofilms was detected by tube method. Results: Thirty Y. enterocolitica isolates (14.29%) were recovered including 19 (15.83%) isolates from chicken meat, 3 (10%) from ground beef, 5 (16.67%) from beef burger, and 3 (10%) from sausage samples. Regarding ail gene, it was detected in 6.67% (2/30), while yst gene detected in 20% (6/30) Y. enterocolitica isolates. About 80%, 70%, 63.33%, and 50% of Y. enterocolitica isolates were sensitive to ciprofloxacin, gentamicin, cefotaxime, and streptomycin, respectively, while 83.33% of Y. enterocolitica isolates were resistant to both ampicillin and cephalothin. Interestingly, 21 (70%) isolates had the capability of biofilms formation in vitro. Among the multidrug-resistant (MDR) strains, a significant difference (p<0.05) was found between MDR and biofilm formation. However, biofilm formation was correlated with the resistance of the isolates to β-lactam antimicrobials and the presence of β-lactam-resistant genes. Conclusion: The presence of Y. enterocolitica in chicken meat, ground and processed beef meat represents a significant health risk for meat consumers, which reflects the contamination of slaughterhouses and processing operations, therefore, strict hygienic measures should be applied to minimize carcasses contamination.
Risk factors associated with cows' lying time, stall and cows' own cleanliness in smallholder dairy farms in Kenya
Authors: Kathambi E. K. , VanLeeuwen J. A. , Gitau G. K. , Kamunde C.
Published: July 2019

Background and Aim: The welfare of animals kept in livestock production systems has raised concerns around the world. Adult dairy cattle require adequate rest and spend approximately 12 h/day lying down. This cross-sectional study aimed to determine the stall factors and management practices affecting cows' lying time, stall cleanliness, and cows' cleanliness (udder and upper leg), in smallholder dairy cows in Meru County of Kenya.

Materials and Methods: A total of 106 milking cows from 73 farms were assessed for daily lying time and cleanliness. Data loggers were used to record the lying time of cows for 3 days. Stall, udder, and upper leg cleanliness were assessed using a 5-score system: 1 (very clean) to 5 (very dirty). Management information was acquired using a questionnaire that was administered face-to-face to the farmers in their native Kimeru language. Univariable and multivariable linear and logistic regression models were fit to determine factors associated with cows' lying time and dichotomized stall and cows' own cleanliness, respectively.

Results: The mean daily lying time was 10.9±2.2 h, and the mean stall cleanliness score was 2.4±1.0. The mean average cleanliness scores of the udder and upper legs were 1.9±0.7 and 2.5±1.1, respectively. Overall, 35% of the stalls were categorized as dirty (>2.5), whereas 13% and 47% of the cows had udder and leg cleanliness scores >2.5, respectively. From the final multivariable models (p<0.05), daily lying time increased by 1.0 h for cows older than 5.25 years versus younger cows. Conversely, lying time decreased by 1.0 h with stall cleanliness scores >2.5 and by 1.6 h with poorly positioned neck rails. In an interaction term, addition of new bedding at least once a day without removing stall manure at least once a day decreased the daily lying time of the cows by 1.5 h, whereas failure to add new bedding at least once a day but removing stall manure at least once a day decreased the lying time of the cows by 1.2 h. Farm-level risk factors for stall dirtiness (>2.5) included delayed cleaning of the alley (odds ratio [OR]=6.6, p=0.032), lack of bedding (OR=4.9, p=0.008), and standing idle and/or backward in the stall (OR=10.5, p=0.002). Stalls categorized as dirty (OR=2.9, p=0.041) and lack of bedding (OR=2.7, p=0.065) were cow- and farm-level risk factors for dirtiness of the udder (>2.5), respectively, whereas the stall being dirty (OR=2.3, p=0.043) was the only risk factor (cow level) for dirtiness of the upper legs (>2.5).

Conclusion: It was recommended that farmers should pay attention to the specific factors identified regarding the stall design (e.g., neck rail position) and bedding/manure management that impact the cleanliness of cows and their lying time.
P003 Young Investigator The role of probiotics in primary and secondary prevention of pouchitis: A systematic review and meta-analysis
Authors: Shadi Hamdeh , Osama Altayar , Jihan Fathallah , Leonard Baidoo , Stephen Hanauer
Published: July 2019

BACKGROUND:

Pouchitis is the most common long-term complication after ileal pouch anal anastomosis (IPAA) surgery. Its cumulative incidence is approximately 50% after a 10-year follow up. Several trials have looked at the use of probiotics in prevention of pouchitis, and showed a significant decrease in the development of pouchitis, but other showed no difference. Our data is very limited and the most recent Cochrane review in 2015 showed a possible benefit of probiotics in maintaining the remission, but it's not widely used in practice, especially in primary prevention. In this systematic review and meta-analysis, we aimed to discern whether probiotics are actually beneficial in primary and secondary prevention of pouchitis.

METHODS:

A comprehensive search of MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews was conducted from each database's inception to May 20, 2017 to search for comparative studies of probiotics use in the prevention of primary (first episode) and secondary (recurrent episodes) pouchitis. The outcome of interest was the development of pouchitis.

RESULTS:

Nine studies with a total of 376 patients were included. The use of probiotics in the primary prevention was associated with a decreased incidence of pouchitis (RR, 0.18; 95% CI, 0.08–0.39; P < 0.01; heterogeneity I2: 0%) with a NNT of 3.2, and their use in the secondary prevention was associated with a decreased incidence of recurrent pouchitis compared to placebo (RR, 0.20; 95% CI, 0.11–0.36; P < 0.01; heterogeneity I2: 0%). Overall risk of developing pouchitis was decreased with the use of probiotics use (RR, 0.19; 95% CI, 0.12–0.30; P < 0.01; heterogeneity I2: 0%) with a NNT of 2. Sub-group analysis included only studies that used VSL#3 showed a significant decrease in pouchitis in both primary prevention (RR, 0.23; 95% CI, 0.10–0.50; P < 0.01; heterogeneity I2: 0%), secondary prevention (RR, 0.17; 95% CI, 0.09–0.31; P < 0.01; heterogeneity I2: 0%), and overall risk (RR, 0.19; 95% CI, 0.12–0.36; P < 0.01; heterogeneity I2: 0%).

CONCLUSION(S):

The current systematic review and meta-analysis showed that probiotics are superior to placebo in the primary and secondary prevention of pouchitis with a very significant NNT. These findings suggest the use of probiotics in patients after ileal pouch anal anastomosis (IPAA) surgery for primary prevention, or in patients with recurrent pouchitis.
P005 Trends of hospitalization in ulcerative colitis in patients in the United States from 2000 to 2014
Authors: Prashanth Rawla , Tagore Sunkara
Published: July 2019

BACKGROUND:

The prevalence of ulcerative colitis (UC) has increased over time and is one of the most important gastrointestinal causes of frequent admissions to hospital in the United States. The cost burden of UC has been steadily increasing. The primary objective of our study was to analyze patient demographics, cost burden, mortality and length of stay associated with UC hospital admissions.

METHODS:

Nationwide inpatient sample (NIS) database was used to identify UC discharges in all patients from 2000 to 2014 using ICD-9-CM Codes (ICD9), Principal Diagnosis: 556.0 Ulcerative Enterocolitis, 556.1 Ulcerative Ileocolitis, 556.2 Ulcerative Proctitis, 556.3 Ulcerative Proctosigmoidtis, 556.4 Pseudopolyposis Colon, 556.5 Left sided Ulcerative Colitis, 556.6 Universal Ulcerative Colitis, 556.8 Other Ulcerative Colitis, 556.9 Ulcerative Colitis Unspecified as the principal discharge diagnosis. NIS is the largest all-payer inpatient care database in the United States, containing data on more than 7 million hospital stays. It has a large sample size which is ideal for developing national and regional estimates.

RESULTS:

A total of 517,191,644 discharges with a diagnosis of UC were analyzed from 2000 to 2014 from the NIS database. The number of hospitalizations increased from 27,452 in 2000 to 37,565 in 2014, a 36.8% increase. In-hospital mortality decreased from 0.94% in 2000 to 0.39% in 2014, a decrease of 58.5%. Mean length of hospital stay has decreased from 6.9 days to 5.8 days (15.9% decrease) during the same period, but the mean hospital charges increased from $18,552 in 2000 to $45,465 in 2014 (145% increase). The proportion of males to females with UC is slowly trending up from 2000 to 2014. Aggregate charges increased from 0.51 billion dollars to 1.70 billion dollars.

CONCLUSION(S):

Overall in-hospital mortality associated with UC has decreased but the number of hospitalizations and mean cost has increased over the years. This represents a significant cost burden on the healthcare system and patients. The decrease in mortality can be attributed to early diagnosis and early institution of newer and aggressive treatments. The number of hospitalizations due to UC has been steadily increasing, and further research needs to be done on finding out the reasons for increased causes of hospitalization and ways to decrease the cost burden on patients and hospitals.
P006  Probiotics treatment in Crohn's disease: A systematic review and meta-analysis of randomized clinical trial
Authors: Muhammed Elfaituri , Alkomos Mina Fransawy , Ammar Kalo , Nguyen Thi Linh Hue , Abdulmoate Alshareef , Mai Nhu Y. , Nada Gaballa , Tran Loc , Bisher Sawaf , Saed Enabi , Sherihan E. Galal , Tarek Ahmed , Thai Le Ba Nghia , Nguyen Tien Huy
Published: July 2019

BACKGROUND:

Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD) is chronic idiopathic, relapsing nonspecific inflammatory characterized by transmural inflammation can involve any element of the gastrointestinal tract, although its etiology is unclear yet, the recent studies have shown the associations between the alteration of gut microbiota and CD, furthermore, several studies suggest using probiotic, prebiotic, and synbiotic agents to manipulate the gut microbiota in the management of Crohn's disease. This study aims to bring together the evidence available on the clinical effect of probiotics in Crohn's disease patients.

METHODS:

To identify all relevant studies, PubMed, MEDLINE, Scopus, Web of Science, and other databases were searched. Randomized clinical trials (RCTs) compared probiotic treatment with placebo were included in this meta-analysis. Primary outcomes were clinical remission and maintenance of remission. Secondary outcomes were adverse events, relapse rate, and endoscopic recurrence rate.

RESULTS:

Eight randomized clinical trials (RCTs) studies were included for meta-analysis. In the probiotic group, there was no significant difference in term of clinical remission compared to placebo, with an odds ratio of 0.89 (95% CI, 0.33–2.35; P > 0.05). Also, there was no significant difference in terms of adverse events rate between the 2 groups with 62 out of 162 (38.2%) in the probiotic group compared with 59 out of 162 (36.4%) in placebo groups; odds ratio 1.08 (95% CI, 0.08–1.78; P > 0.05). On the other hand, there was no significant difference in terms of relapse rate between 2 groups with 52 out of 124 (41.9%) in the probiotic group compared with 52 out of 121 (42.9%) in placebo groups; odds ratio 0.99 (95% CI, 0.58–1.69; P > 0.5). Regarding endoscopic recurrence rate, there was no significant difference in 2 groups of patients who underwent postoperative follow-up with 76 out of 137 (55.4%) in the probiotic group compared with 88 out 147 (59.8%) in placebo groups; odds ratio 0.86 (95% CI, 0.52–1.42; P > 0.05).

CONCLUSION(S):

Probiotic is potentially useful in Crohn's disease management. However, it appears to be effective for induction of remission, but with no significant major short-term benefits compared to the placebo group. Finally, there remain many unanswered questions that require further studies before probiotic can be considered for use in the treatment of Crohn's disease.
P007 Treatment of IBD with proton pump inhibitors: Implications for periodontal disease
Authors: Lisa Yerke , Michael Levine , Robert Cohen
Published: July 2019

BACKGROUND:

Previous studies have shown that an increased risk of complications from Crohn's disease and ulcerative colitis (IBD) is associated with the use of proton pump inhibitors (PPI). PPI can reduce the clinical manifestations of gastrointestinal reflux disease, but also may affect the gastrointestinal and oral microbiota as well as influence bone metabolism. IBD has been positively associated with an inflammatory host response following bacterial infection characteristic of periodontal disease (PD). Consequently, we hypothesized that the severity of PD might be related to the use of PPI. Such a relationship in a patient taking PPI might affect treatment decisions related to both IBD and periodontitis.

METHODS:

This retrospective study was reviewed and approved by the State University of New York at Buffalo (SUNYAB) Institutional Review Board. To test our hypothesis, we examined medical and dental history records of patients aged ≥35 years old that were referred to the SUNYAB School of Dental Medicine postgraduate periodontics program for periodontal evaluation from 2010 to 2017 (N = 1,017). From that group, patients diagnosed with generalized, chronic, moderate-to-severe periodontitis were used in this study (N = 581). To measure PD severity, we calculated the number of teeth with periodontal pocket depths ≥6 mm for each patient. Use of PPI medications was confirmed by review of patient medical records. Populations were adjusted for smoking and diabetes. Significance was measured via computation of the 95% confidence interval and P-value of the difference between the means of each group using IBM SPSS Statistics v25.

RESULTS:

We found that there was an inverse relationship between use of PPI and severity of PD. Specifically, 15.7% of teeth from PD patients taking PPI had periodontal pocket depths ≥6 mm, vs 22.6% of teeth in PD patients not taking PPI (mean difference, 6.9%, 30.5% decrease; 95% confidence interval, 2.2%–11.5%; P = 0.004). After adjusting for diabetes and smoking, this relationship persisted: The prevalence of pocket depths ≥6 was 12.7% in PD patients taking PPI, vs 19.7% for PD patients not taking PPI (mean difference, 7.0%; 35.5% decrease; 95% confidence interval, 3.0%–11.0%; P = 0.0008).

CONCLUSION(S):

In patients with chronic, generalized, moderate-to-severe periodontitis, our results suggest that use of PPI is associated with smaller periodontal pocket depths, implying less severe PD. The data indicate that more conservative periodontal therapy might initially be considered for IBD patients with advanced periodontal disease for whom PPI are prescribed as a component of their IBD treatment. Prospective studies currently are being developed to determine if PPI can directly modify the course of PD, or if the association between PPI and PD is related to immunologic or microbiologic factors associated with IBD. This study was supported in part by the W.M. Feagans Endowed Chair Fund, and the Department of Periodontics and Endodontics, SUNY Buffalo.
P009 A comparison of pediatric vs adult onset IBD in Puerto Rican Hispanics
Authors: Karelys Burgos , Anna Blanco , Natalie Emanuelli , Esther Torres
Published: July 2019

BACKGROUND:

The IBD Registry collects demographic and medical information of patients with confirmed ulcerative colitis (UC) and Crohn's disease (CD). The 4-fold increase in IBD in Puerto Rico including children warrants exploration of this population. The aim is to describe clinical features of IBD in pediatric vs adult onset Puerto Ricans.

METHODS:

This is a cross-sectional study in where registry entries from 1995 to 2018 were analyzed for demographics, medical information, family history, extra-intestinal manifestations, surgery, duration of disease and interval between symptom onset and diagnosis using ANOVA. Data was divided into pediatric onset (age of onset ≤18 years old), and adult onset IBD (≥19 years old), then each group was subdivided by disease, CD and UC. The IBD Registry is approved by the Medical Sciences Campus IRB.

RESULTS:

Nine hundred Seven Puerto Ricans with IBD, 541 (59.7%) with CD and 366 (40.3%) with UC, were included. Three hundred fifty-five (39.1%) were pediatric onset and 552 (60.9%) adult onset IBD. Mean age of onset was 31.6 ± 11.6 in adult onset and 14.1 ± 3.8 in pediatric onset patients. Two hundred ninety-five patients had at least one extra-intestinal manifestation, 40.5% in the adult onset and 20% in the pediatric onset group. Arthritis was the most common extra-intestinal manifestation in both groups. Family history of IBD was present in 33.5% and 18.7% of pediatric and adult onset, respectively (P = 0.2). Pediatric onset subjects had a higher prevalence of remote relatives with IBD (21.3% vs 13.2% of the adults, P < 0.05). 71.4% of the adult onset IBD patients and 36.6% of the pediatric had ≤5 years with disease. Interval less than 1 year between onset of symptoms and diagnosis in the pediatric group was 55% for UC and 45.1% for CD. For the adult group, 64.2% and 51.5% of UC and CD respectively were diagnosed within a year. Prevalence of surgery was 30.9% and 55.8% for all UC and CD respectively (P = 0.002); and 47.3% for pediatric and 44.7% for adults (P = 0.6).

CONCLUSION(S):

Significant differences between pediatric and adult onset Puerto Ricans with IBD were a higher prevalence of EIM in adults and a higher proportion of non-first-degree relatives with IBD in pediatrics. As expected, the prevalence of surgery was higher in patients with CD than in patients with UC in both groups. The majority of patients had 5 years or less of disease and were diagnosed within 1 year of the onset of symptoms. This study contributes to a better understanding of the epidemiology of IBD in Puerto Rican Hispanics.
P010 Results from a new anti-vedolizumab antibody assay
Authors: Maria Rosario , Lili Yang , Timothy Wyant
Published: July 2019

BACKGROUND:

Immunogenicity was assessed in GEMINI I (NCT00783718) and II (NCT00783692) using an enzyme-linked immunosorbent assay (ELISA).
1,2
It was later determined that the presence of ∼0.5 μg/mL of vedolizumab interferes with the ELISA, which potentially might have underestimated on-drug immunogenicity. Therefore, a new acid dissociation electrochemiluminescence (ECL) anti-vedolizumab antibody (AVA) assay was developed with a drug tolerance of ≥50 μg/mL. In addition, a more drug-tolerant ECL assay was developed to quantify the ability of AVAs to neutralize vedolizumab (neutralizing assay). The current study reassessed vedolizumab immunogenicity using banked serum samples from GEMINI I and II with the ECL assays.

METHODS:

Positive or negative AVA status was determined according to the previous ELISA assay definitions, and overall AVA positivity was summarized using descriptive statistics. The effect of AVA on vedolizumab pharmacokinetics (PK) was assessed using a previously reported population PK model 1 that was updated with data from the ECL assay. Serum samples from 1,427 of 1,434 patients who received continuous treatment with vedolizumab for 52 weeks were available for reanalyses. Samples confirmed as AVA positive were further characterized using the neutralizing assay.

RESULTS:

With the ECL assay, 6% (86/1,427) of patients were AVA positive at any time during the study. Of these, 20 patients were considered persistently positive (confirmed AVA positive in ≥2 consecutive AVA samples) and 56 had neutralizing antibodies. With the ELISA, 4% (56/1,434) of patients were AVA positive at any time. Of these, 9 patients were considered persistently positive and 33 had neutralizing antibodies.
2
Parameter estimates, precision of PK structural parameters, interindividual and residual variabilities, and covariate effects (including AVA effects) were comparable between the previous and updated final population PK models. Therefore, inferences regarding the clinical relevance of covariates were also similar between the 2 PK models. In the updated PK model, AVA presence was estimated to increase vedolizumab linear clearance (CLL) by a factor of 1.10 (95% credible interval [CDI]: 1.03, 1.17), consistent with the previous final model where AVA was estimated to increase CLL by a factor of 1.12 (95% CDI: 1.05, 1.2). With the ECL assay, of the 61 patients who had an adverse event assessed by the investigator as an infusion-related reaction, 6 (10%) were AVA positive, 2 of whom were persistently positive. With the prior ELISA, 3 of 61 (5%) patients were AVA positive, all 3 of whom were persistently positive.
2

CONCLUSION(S):

Vedolizumab immunogenicity rates and PK were similar between the ECL and ELISA assays. Compared to the ELISA assay, the ECL assay detected slightly more AVA-positive patients among patients with infusion reactions.
P013 Fecal calprotectin predicts relapse in UC patients with histological remission
Authors: Sung Jung , Bum Kim Dae , Kang-Moon Lee , Min Lee Ji
Published: July 2019

BACKGROUND:

Histological remission has been recognized as the treatment goal of ulcerative colitis (UC). We aim to investigate the factors that predict relapse in UC patients with histological remission.

METHODS:

We performed a prospective study of patients with UC from March 2014 to February 2016. If patients have mucosal healing during endoscopy, several biopsy specimens were collected from sigmoid colon and rectum. An expert pathologist evaluated colonic biopsies for histological activity (Geboes score). Histological remission was defined as a Geboes score <3.1. Demographic data, serological data including hemoglobin, hematocrit, white blood cell and platelet counts, albumin, C-reactive protein, and fecal calprotectin (FC) within a week of endoscopy were collected.

RESULTS:

Of the 36 patients in histological remission, 9/36 (25%) relapsed after a median follow-up of 29 months (range 2-45 months). FC was significantly higher in patients who relapsed compared with patients who maintained clinical remission (153.7 μg/g vs 103.4 μg/g; p = 0.047). In multivariate analysis, the FC was only independent predictors of relapse. A receiver operating characteristic analysis estimated a cutoff level of >134.6 μg/g for FC (area under the curve, 0.758 and confidence interval 95%, 0.579–0.937) for predicting relapse during follow-up with 77.8% sensitivity, 74.1% specificity.

CONCLUSION(S):

High FC levels can predict relapse in patients with UC. Therefore, regular measurement of FC should be considered in UC patients, even if they have histological remission.