bluuebunny/crossref_metadata_2025_split huggingface dataset:
The incidence of tuberculosis in patients treated with certolizumab pegol across indications: impact of baseline skin test results, more stringent screening criteria and geographic region
Authors: Mariette X , Vencovsky J , Lortholary O , Gomez-Reino J , de Longueville M , Ralston P , Weinblatt M , van Vollenhoven R 
Published: April 2015

ObjectivesWe report the incidence of tuberculosis (TB) across certolizumab pegol (CZP) clinical trials in rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), before and after the introduction of stricter TB screening.MethodsTB incidence rates (IRs) were assessed and stratified according to screening guidelines used at the time of CZP trials. Before 2007 (originaltrials), purified protein derivative (PPD) tuberculin skin test positivity varied according to local standards (induration ≥5 up to ≥20 mm). Since 2007, all CZP trial protocols have been amended, including trials spanning (intermediate) and initiated after 2007 (current), mandating that any patient with PPD≥5 mm receives treatment for latent TB infection (LTBI). All cases of suspected TB or PPD≥5 mm, in pooled data from 5402 CZP patients across all CZP trials up to 2012, underwent blinded central review by independent experts.Results44 TB cases were confirmed in pooled CZP RA trials (IR 0.47/100PY, patient-years) with no cases in Japanese RA trials (J-RAPID, HIKARI). Single TB cases were confirmed in psoriasis and axSpA trials (RAPID-axSpA), and no cases in the PsA trial (RAPID-PsA). IR of TB was 0.51/100PY acrossoriginalorintermediateRA trials and 0.18/100PY incurrenttrials. The majority of TB cases in RA occurred in Eastern (IR 1.02/100PY) and Central Europe (IR 0.58/100PY). Of 242/370 PPD≥5 mm patients who received 9 months isoniazid (INH) treatment for latent TB infection (LTBI), none developed TB, versus 7.8% of 128 untreated PPD≥5 mm patients.ConclusionsImplementation of more stringent LTBI screening, plus treatment for LTBI, reduced the IR of TB, even when INH was administered after starting CZP therapy.
Ipilimumab-Induced Encephalopathy with a Reversible Splenial Lesion
Authors: Conry Robert M. , Sullivan Joseph C. , Nabors Louis B. 
Published: April 2015

Abstract
Ipilimumab, an anticytotoxic T-lymphocyte antigen (CTLA)-4 monoclonal antibody, is a first-line therapy for stage IV melanoma. Although high-grade immune-related adverse events occur in 25% of patients receiving ipilimumab, serious neurologic toxicity, primarily consisting of transient sensory and motor neuropathies, affects less than 1% of patients. We present a case report of a patient with melanoma who received high-dose ipilimumab at 10 mg/kg as first-line therapy for metastatic disease. After the third dose, the patient developed “mild” encephalopathy with a reversible splenial lesion (MERS) of the corpus callosum by MRI and neurogenic bladder, two novel immune-related adverse events during checkpoint inhibition. In addition to headache, delirium, and altered consciousness commonly seen with MERS, the patient also developed tremor, gait instability, paresthesias, and neurogenic bladder. The latter two symptoms were thought to represent sensory and autonomic neuropathies, respectively. The syndrome gradually resolved following intravenous methylprednisolone at 2 mg/kg divided twice daily for 5 days and a slow taper of oral prednisone over 8 weeks. Cancer Immunol Res; 3(6); 598–601. ©2015 AACR.
Chronic Elevation of Tumor Necrosis Factor-α Mediates the Impairment of Leptomeningeal Arteriogenesis in db/db Mice
Authors: Yukami Toshiro , Yagita Yoshiki , Sugiyama Yukio , Oyama Naoki , Watanabe Akihiro , Sasaki Tsutomu , Sakaguchi Manabu , Mochizuki Hideki , Kitagawa Kazuo 
Published: April 2015

Background and Purpose—
Leptomeningeal collateral growth is a key factor that defines the severity of ischemic stroke. Patients with stroke generally have vascular risk factors, such as diabetes mellitus; however, consensus is lacking on how diabetes mellitus affects leptomeningeal arteriogenesis. We investigate the influence of diabetes mellitus on the leptomeningeal arteriogenesis.

Methods—
We measured the vessel diameter of the leptomeningeal anastomoses 14 days after the common carotid artery occlusion in db/db, db/+, and streptozotocin-induced hyperglycemic mice. In another set of these mice, we measured the infarct volume attributed to subsequent middle cerebral artery occlusion 14 days after the common carotid artery occlusion. Mac-2–positive cells on the dorsal brain surface and the mRNA expression of several macrophage-related factors in the cerebral cortex were examined. Finally, we tested whether the leptomeningeal arteriogenesis could be restored by pharmaceutical intervention in the db/db mice.

Results—
Cerebral hypoperfusion led to significant ipsilateral leptomeningeal collateral growth in db/+ mice and streptozotocin-induced hyperglycemic mice. The collateral growth contributed to reduced infarct volume. In contrast, leptomeningeal arteriogenesis was impaired in the db/db mice. The number of Mac-2–positive cells was increased and tumor necrosis factor-α mRNA expression was induced after common carotid artery occlusion in the db/+ mice. However, these responses were not observed in the db/db mice. Administration of the tumor necrosis factor-α inhibitor etanercept before common carotid artery occlusion restored the hypoperfusion-induced leptomeningeal collateral growth in db/db mice.

Conclusions—
These results indicate that leptomeningeal arteriogenesis is impaired in db/db mice and that suppression of the tumor necrosis factor-α response to hypoperfusion is the major contributing factor.
Myeloperoxidase Is Increased in Human Cerebral Aneurysms and Increases Formation and Rupture of Cerebral Aneurysms in Mice
Authors: Chu Yi , Wilson Katina , Gu He , Wegman-Points Lauren , Dooley Sarah A. , Pierce Gary L. , Cheng Guangjie , Pena Silva Ricardo A. , Heistad Donald D. , Hasan David 
Published: April 2015

Background and Purpose—
Cerebral aneurysm (CA) affects 3% of the population and is associated with hemodynamic stress and inflammation. Myeloperoxidase, a major oxidative enzyme associated with inflammation, is increased in patients with CA, but whether myeloperoxidase contributes to CA is not known. We tested the hypotheses that myeloperoxidase is increased within human CA and is critical for formation and rupture of CA in mice.

Methods—
Blood was drawn from the lumen of CAs and femoral arteries of 25 patients who underwent endovascular coiling of CA, and plasma myeloperoxidase concentrations were measured with ELISA. Effects of endogenous myeloperoxidase on CA formation and rupture were studied in myeloperoxidase knockout mice and wild-type (WT) mice using an angiotensin II–elastase induction model of CA. In addition, effects of myeloperoxidase on inflammatory gene expression in endothelial cells were analyzed.

Results—
Plasma concentrations of myeloperoxidase were 2.7-fold higher within CA than in femoral arterial blood in patients with CA. myeloperoxidase-positive cells were increased in aneurysm tissue compared with superficial temporal artery of patients with CA. Incidence of aneurysms and subarachnoid hemorrhage was significantly lower in myeloperoxidase knockout than in WT mice. In cerebral arteries, proinflammatory molecules, including tumor necrosis factor-α, cyclooxygenase-2 (COX2), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C motif) ligand (XCL1), matrix metalloproteinase (MMP) 8, cluster of differentiation 68 (CD68), and matrix metalloproteinase 13, and leukocytes were increased, and α-smooth muscle actin was decreased, in WT but not in myeloperoxidase knockout mice after induction of CA. Myeloperoxidase per se increased expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in endothelial cells.

Conclusions—
These findings suggest that myeloperoxidase may contribute importantly to formation and rupture of CA.
Cancer in Young Adults With Ischemic Stroke
Authors: Aarnio Karoliina , Joensuu Heikki , Haapaniemi Elena , Melkas Susanna , Kaste Markku , Tatlisumak Turgut , Putaala Jukka 
Published: April 2015

Background and Purpose—
Cancer is a risk factor for ischemic stroke. Little is known about cancer among young adults with ischemic stroke. We studied the frequency of cancer and its association with long-term risk of death among young patients with first-ever ischemic stroke.

Methods—
1002 patients aged 15 to 49 years, registered in the Helsinki Young Stroke Registry, and with a median follow-up of 10.0 years (interquartile range 6.5–13.8) after stroke were included. Historical and follow-up data were derived from the Finnish Care Register and Statistics Finland. Survival between groups was compared with the Kaplan–Meier life-table method, and Cox proportional hazard models were used to identify factors associated with mortality.

Results—
One or more cancer diagnosis was made in 77 (7.7%) patients, of whom 39 (3.9%) had cancer diagnosed prestroke. During the poststroke follow-up, 41 (53.2%) of the cancer patients died. Median time from prestroke cancer to stroke was 4.9 (1.0–9.5) years and from stroke to poststroke cancer was 6.7 (2.7–10.9) years. Poststroke cancer was associated with age >40 years, heavy drinking, and cigarette smoking. The cumulative mortality was significantly higher among the cancer patients (68.6%, 95% confidence interval 52.0%–85.3%) compared with patients without cancer (19.7%, 95% confidence interval 16.3%–23.2%). Active cancer at index stroke, melanoma, and lung/respiratory tract cancer had the strongest independent association with death during the follow-up when adjusted for known poststroke mortality prognosticators.

Conclusions—
Cancer, and especially active cancer and no other apparent cause for stroke, is associated with unfavorable survival among young stroke patients.
Dying in the hospital setting: A systematic review of quantitative studies identifying the elements of end-of-life care that patients and their families rank as being most important
Authors: Virdun Claudia , Luckett Tim , Davidson Patricia M , Phillips Jane 
Published: April 2015

Background: The majority of expected deaths occur in hospitals where optimal end-of-life care is not yet fully realised, as evidenced by recent reviews outlining experience of care. Better understanding what patients and their families consider to be the most important elements of inpatient end-of-life care is crucial to addressing this gap. Aim and design: This systematic review aimed to ascertain the five most important elements of inpatient end-of-life care as identified by patients with palliative care needs and their families. Data sources: Nine electronic databases from 1990 to 2014 were searched along with key internet search engines and handsearching of included article reference lists. Quality of included studies was appraised by two researchers. Results: Of 1859 articles, 8 met the inclusion criteria generating data from 1141 patients and 3117 families. Synthesis of the top five elements identified four common end-of-life care domains considered important to both patients and their families, namely, (1) effective communication and shared decision making, (2) expert care, (3) respectful and compassionate care and (4) trust and confidence in clinicians. The final domains differed with financial affairs being important to families, while an adequate environment for care and minimising burden both being important to patients. Conclusion: This review adds to what has been known for over two decades in relation to patient and family priorities for end-of-life care within the hospital setting. The challenge for health care services is to act on this evidence, reconfigure care systems accordingly and ensure universal access to optimal end-of-life care within hospitals.
Anatomical Reconstruction of Lateral Ankle Ligaments Using Free Tendon Allografts and Biotenodesis Screws
Authors: Jung Hong-Geun , Shin Min-Ho , Park Jong-Tae , Eom Joon-Sang , Lee Dong-Oh , Lee Sang-Hun 
Published: April 2015

Background: Lateral ankle instability is one of the most common musculoskeletal disorders and can result in ankle damage. This study reports on the results of the anatomical reconstruction of ligaments using semitendinosus tendon allograft and bioabsorbable tenodesis screws for chronic lateral ankle instability, as well as the functional and radiological results of this procedure. Methods: From February 2007 to January 2013, 70 patients (72 ankles) underwent this procedure. Six patients were lost to follow-up, and ultimately 64 patients (66 ankles) were evaluated. Visual Analog Scale (VAS) pain scores, American Orthopaedic Foot & Ankle Society (AOFAS) scores, Karlsson-Peterson ankle scores, and patient satisfaction were evaluated at a mean of 22.1 months (range, 12-68 months) postoperatively. The talar tilt angle and anterior translation were assessed radiographically in pre- and postoperative ankle stress views. The mean patient age at surgery was 30.1 years (range, 16-59 years). Results: The mean VAS pain score decreased from 5.5 to 1.3 ( P < .05), and the mean AOFAS improved from 71.0 to 90.9 ( P < .05). The mean Karlsson-Peterson score improved from 55.1 to 90.3, whereas talar tilt decreased from 14.8 degrees to 3.9 degrees. There was no significant difference in clinical outcomes between the pretensioned and nonpretensioned groups. Conclusion: This procedure yielded successful results, including satisfactory ankle stability and clinical outcomes, in ankles with poor lateral ligament tissues. Level of Evidence: Level IV, case series.
Treatment of acute relapses in neuromyelitis optica: Steroids alone versus steroids plus plasma exchange
Authors: Abboud Hesham , Petrak Alex , Mealy Maureen , Sasidharan Sarana , Siddique Laila , Levy Michael 
Published: April 2015

Background: Although adding plasma exchange (PLEX) to steroids in severe neuromyelitis optica (NMO) attacks is common practice in steroid-resistant cases, the benefit of this strategy has not been previously quantified. Objective: The objective of this paper is to compare the efficacy of high-dose intravenous methylprednisolone (IVMP) versus IVMP+PLEX in treatment of acute NMO relapses. Methods: We conducted a retrospective review of the last 83 NMO admissions to the Johns Hopkins Hospital treated with IVMP alone versus IVMP+PLEX (for steroid-resistant cases). Extended Disability Status Scale (EDSS) score was calculated at baseline, at presentation, at discharge, and on follow-up. Results: Eighteen NMO relapses (16 patients, 87% female, mean age at relapse: 33.9±23.8, median baseline EDSS 2.5) were treated with IVMP alone and 65 relapses (43 patients, 95% female, mean age at relapse: 43.8±15.7, median baseline EDSS 5.75) were treated with IVMP + PLEX. Sixty-five percent of IVMP + PLEX patients achieved an EDSS equal or below their baseline at follow-up while only 35% of the IVMP-only patients achieved their baseline EDSS on follow-up (odds ratio=3.36, 95% CI 1.0657 to 10.6004, p = 0.0386). PLEX was more effective in improving EDSS in patients on preventive immunosuppressive medications at time of relapse. Conclusions: PLEX+IVMP are more likely to improve EDSS after NMO relapses compared to IVMP alone, especially in patients taking preventive medications.
HLA associations in South Asian multiple sclerosis
Authors: Pandit Lekha , Malli Chaithra , Singhal Bhim , Wason James , Malik Omar , Sawcer Stephen , Ban Maria , D’Cunha Anitha , Mustafa Sharik 
Published: April 2015

Background: Previous efforts to identify Human Leukocyte Antigen (HLA) gene associations with multiple sclerosis (MS) in the South Asian population have been underpowered. Aim: To identify the primary HLA class II alleles associated with MS in Indians. Methods: We typed HLA-DRB1, -DQA1 and -DQB1 in 419 patients and 451 unrelated controls by polymerase chain reaction using sequence specific oligonucleotide probes (PCR-SSOP). Results: At the gene level DRB1 showed significant evidence of association ( p=0.0000012), DQA1 showed only marginal evidence of association ( p=0.04) and there was no evidence for association at DQB1 ( p=0.26). At the DRB1 locus association is confirmed with the *15:01 ( p=0.00002) and the *03 ( p=0.00005) alleles. Conclusion: Our study confirms that the risk effects attributable to the HLA- DRB1*15:01and DRB1*03 alleles seen in Europeans are also seen in Indians. The absence of any evidence of association with DQB1 alleles reflects the lower linkage disequilibrium between DQB1 alleles and DRB1 risk alleles present in this population, and illustrates the potential value of fine mapping signals of association in different ethnic groups.
Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia
Authors: Hadjixenofontos A , Gourraud PA , Bakthavachalam V , Foco L , Ticca A , Bitti P , Pastorino R , Bernardinelli L , McCauley JL 
Published: April 2015

Background: The list of genomic loci associated with multiple sclerosis (MS) susceptibility outside the major histocompatibility complex (MHC) in patients of Northern European (NE) ancestry has increased to 103. Despite the extraordinarily high MS prevalence in the isolated Sardinian population, the contribution of genetic risk factors to MS in Sardinia is largely not understood. Objective: The objective of this paper is to examine the relevance of non-MHC MS susceptibility variants in Sardinia. Methods: We examined a log-additive MS-specific genetic burden score (MSGB) using 110 NE-derived risk alleles in a dataset of 75 Sardinian cases, 346 Sardinian controls and 177 cases and 1967 controls from the United States (US). Results: Sardinian cases demonstrate a heavier non-MHC MSGB load than Sardinian controls and US cases ( p = 2E-06, p = 1E-06, respectively). Furthermore, Sardinian controls carry a heavier burden than US controls ( p = 2E-14). Our results confirm the limited ability of the 110-SNP MSGB to predict disease status in Sardinia (AUROC = 0.629). Conclusions: Risk alleles discovered in samples of NE ancestry are relevant to MS in Sardinia. Our results suggest a general enrichment of MS susceptibility alleles in Sardinians, encouraging the pursuit of further studies of MS in this population.
Feasibility of Day Surgery in Patients With Breast Conservation and Sentinel Node Biopsy: A Randomized Controlled Trial
Authors: Ojala K. , Vironen J. H. , Mattila K. , Eklund A. M. , Leidenius M. H. K. , Meretoja T. J. 
Published: April 2015

Background and Aims: The aim of this study was to analyze feasibility of day surgery in breast cancer patients with breast conserving surgery and sentinel node biopsy. Material and Methods: The study was a randomized controlled trial comparing day surgery with one night hospital stay in breast cancer patients with breast conserving surgery and sentinel node biopsy. A total of 40 patients with ⩽3-cm tumor and clinically N0 were randomized to one night stay group and 38 patients to day surgery group. Within discharge, patients and their relatives were given questionnaires in order to evaluate their experience regarding the duration of hospital stay. Results: Randomized groups were similar regarding patient age and tumor stage. A total of 18 (47%) day surgery group patients were discharged the same day. The most common reason for overnight hospital stay was axillary clearance, 9 (24%). None of the patients in the day surgery group, but 2 patients in the overnight hospital stay group had re-operation due to complications. Perception and preference results were analyzed both according to randomization and actual treatment groups. Patients in both groups had rather similar experiences on the first postoperative day. Also, spouse’s or relative’s perception after discharge was similar in both groups. Conclusion: Day surgery was well received by the patients and their relatives. Day surgery appears as feasible in patients with breast conservation and sentinel node biopsy.
Feasibility study of minimal prepared hydroflush screening colonoscopy
Authors: Moshkowitz Menachem , Fokra Ahmad , Itzhak Yoseph , Arber Nadir , Santo Erwin 
Published: April 2015

BackgroundAlthough screening colonoscopy is effective for early detection of colorectal cancer (CRC), screening rates remain low. Multiple factors are thought to be responsible for the low rates of screening colonoscopy, but bowel preparation appears to be a key deterrent. Tolerability issues with bowel preparations may lead to poor patient compliance, inadequate colon cleansing, and reduced detection of colonic polyps.AimThe aim of this article is to evaluate the feasibility, safety, and outcomes of minimally prepared intra‐procedural hydroflush technique as an alternative to traditional bowel preparation in screening colonoscopy.DesignWe conducted a prospective feasibility study of intraprocedural hydroflush technique aided by water‐jet pumps and a mechanical suction novel device following minimal bowel preparation for CRC screening.Patients and methodsNine procedures were performed in nine healthy individuals scheduled for routine screening colonoscopy. Preparation included mild diet restriction, laxative tablets two to three days prior to the procedure and two Fleet enemas one to two hours before the colonoscopy. The cleanliness of the colon was assessed by using the Boston bowel preparation scale. Insertion and withdrawal times were recorded.ResultsComplete colonoscopy to the cecum was performed in all patients (100%). Mean time to the cecum was 5.78 ± 2.68 minutes, and mean withdrawal time was 15.33 ± 3.94 minutes. Endoscopic visualization of the entire mucosa was achieved in all cases with no colonoscopy repeated because of inadequate preparation. Four polyps have been detected and removed in three patients. Mild mucosal erosions were seen in some areas where the suction was used extensively, similar to those that can be seen during conventional colonoscopy. Mild stiffness of the shaft of the scope was noted.LimitationsThis was an uncontrolled feasibility study of selected patients.ConclusionsMinimally prepared colonoscopy with the intra‐procedural hydroflush technique for colorectal screening is feasible. The water exchange technology compensates for the mild stiffness of the scope. This technique might increase patients’ compliance for CRC screening.
Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study
Authors: Linkins Lori-Ann , Bates Shannon M. , Lee Agnes Y. Y. , Heddle Nancy M. , Wang Grace , Warkentin Theodore E. 
Published: April 2015

Key Points
A negative PaGIA test in a patient with low/intermediate 4Ts score excludes HIT with a high level of confidence. A low 4Ts score was insufficient to exclude HIT in some cases because the posttest probability of HIT with a positive PaGIA was moderate.