bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter, randomized comparison between 2, 5, and 8 mg of perineural dexamethasone for ultrasound-guided infraclavicular block
Authors: Bravo Daniela , Aliste Julian , Layera Sebastián , Fernández Diego , Leurcharusmee Prangmalee , Samerchua Artid , Tangjitbampenbun Amornrat , Watanitanon Arraya , Arnuntasupakul Vanlapa , Tunprasit Choosak , Gordon Aida , Finlayson Roderick J , Tran De Q 
Published: January 2019

Background and objectivesThis multicenter, randomized trial compared 2, 5, and 8 mg of perineural dexamethasone for ultrasound-guided infraclavicular brachial plexus block. Our research hypothesis was that all three doses of dexamethasone would result in equivalent durations of motor block (equivalence margin=3.0 hours).MethodsThree hundred and sixty patients undergoing upper limb surgery with ultrasound-guided infraclavicular block were randomly allocated to receive 2, 5, or 8 mg of preservative-free perineural dexamethasone. The local anesthetic agent (35 mL of lidocaine 1%-bupivacaine 0.25% with epinephrine 5 µg/mL) was identical in all subjects. Patients and operators were blinded to the dose of dexamethasone. During the performance of the block, the performance time, number of needle passes, procedural pain, and complications (vascular puncture, paresthesia) were recorded. Subsequently a blinded observer assessed the success rate (defined as a minimal sensorimotor composite score of 14 out of 16 points at 30 min), onset time as well as the incidence of surgical anesthesia (defined as the ability to complete surgery without local infiltration, supplemental blocks, intravenous opioids, or general anesthesia). Postoperatively, the blinded observer contacted patients with successful blocks to inquire about the duration of motor block, sensory block, and postoperative analgesia. The main outcome variable was the duration of motor block.ResultsNo intergroup differences were observed in terms of technical execution (performance time/number of needle passes/procedural pain complications), onset time, success rate, and surgical anesthesia. Furthermore, all three doses of dexamethasone provided similar durations of motor block (14.9–16.1 hours) and sensory block. Although 5 mg provided a longer analgesic duration than 2 mg, the difference (2.7 hours) fell within our pre-established equivalence margin (3.0 hours).Conclusions2, 5, and 8 mg of dexamethasone provide clinically equivalent sensorimotor and analgesic durations for ultrasound-guided infraclavicular block. Further trials are required to compare low (ie, 2 mg) and ultra-low (eg, 0.5–1 mg) doses of perineural dexamethasone for brachial plexus blocks.Trial registration numberTCTR20150624001.
Counting graded lattices of rank 3 that have few coatoms
Authors: Kohonen Jukka 
Published: January 2019

We consider the problem of computing [Formula: see text], the number of unlabeled graded lattices of rank [Formula: see text] that contain [Formula: see text] coatoms and [Formula: see text] atoms. More specifically, we do this when [Formula: see text] is fairly small, but [Formula: see text] may be large. For this task, we describe a computational method that combines constructive listing of basic cases and tools from enumerative combinatorics. With this method, we compute the exact values of [Formula: see text] for [Formula: see text] and [Formula: see text]. We also show that, for any fixed [Formula: see text], there exists a quasipolynomial in [Formula: see text] that matches with [Formula: see text] for all [Formula: see text] above a small value. We explicitly determine these quasipolynomials for [Formula: see text], thus finding closed form expressions of [Formula: see text] for [Formula: see text].
Elevated Vitamin B12 Levels and Cancer Risk in UK Primary Care: A THIN Database Cohort Study
Authors: Arendt Johan F.H. , Sørensen Henrik T. , Horsfall Laura J. , Petersen Irene 
Published: January 2019

Abstract

Background:
Elevated vitamin B12 levels (B12) are associated with increased short-term cancer risk. However, the implications for early cancer detection in primary care have not been assessed.

Methods:
Individuals with plasma B12 measurements were sampled from The Health Improvement Network primary care database, UK. Persons with low B12 levels were excluded together with persons with cancer or B12 treatment before date of B12 measurement. Incident cancer was the outcome of interest and was identified through Read codes. Individuals were disaggregated according to plasma B12 levels (unit: pmol/L): 150–600 (reference range values), 601–800, 801–1,000, and &gt;1,000.

Results:
Among the 757,185 persons who met the inclusion criteria, we identified 33,367 incident cancers during 2,874,059 years of follow-up. We found a higher 1-year cancer risk among the 25,783 (3.4%) persons with elevated B12 levels compared with those with normal B12 levels. After multivariable adjustment for lifestyle factors and social deprivation, persons with B12 &gt;1,000 pmol/L had a 1-year incidence rate ratio of 4.72 (95% confidence interval: 3.99–5.58). The association showed a nonlinear dose–response pattern, and it remained robust in stratified analyses, including when reducing the risk of confounding by indication in subanalyses. The risks were particularly elevated for liver cancer, pancreas cancer, and myeloid malignancies among persons with elevated B12 levels.

Conclusions:
Elevated plasma B12 levels were associated with a higher 1-year cancer risk than normal B12 levels among persons seen in UK primary care, suggesting that some cancers may affect B12 metabolism.

Impact:
Elevated B12 may mark occult cancer.
Targeted Resequencing of the Coding Sequence of 38 Genes Near Breast Cancer GWAS Loci in a Large Case–Control Study
Authors: Decker Brennan , Allen Jamie , Luccarini Craig , Pooley Karen A. , Shah Mitul , Bolla Manjeet K. , Wang Qin , Ahmed Shahana , Baynes Caroline , Conroy Don M. , Brown Judith , Luben Robert , Ostrander Elaine A. , Pharoah Paul D.P. , Dunning Alison M. , Easton Douglas F. 
Published: January 2019

Abstract

Background:
Genes regulated by breast cancer risk alleles identified through genome-wide association studies (GWAS) may harbor rare coding risk alleles.

Methods:
We sequenced the coding regions for 38 genes within 500 kb of 38 lead GWAS SNPs in 13,538 breast cancer cases and 5,518 controls.

Results:
Truncating variants in these genes were rare, and were not associated with breast cancer risk. Burden testing of rare missense variants highlighted 5 genes with some suggestion of an association with breast cancer, although none met the multiple testing thresholds: MKL1, FTO, NEK10, MDM4, and COX11. Six common alleles in COX11, MAP3K1 (two), and NEK10 (three) were associated at the P &lt; 0.0001 significance level, but these likely reflect linkage disequilibrium with causal regulatory variants.

Conclusions:
There was no evidence that rare coding variants in these genes confer substantial breast cancer risks. However, more modest effect sizes could not be ruled out.

Impact:
We tested the hypothesis that rare variants in 38 genes near breast cancer GWAS loci may mediate risk. These variants do not appear to play a major role in breast cancer heritability.
Weighting Nonprobability and Probability Sample Surveys in Describing Cancer Catchment Areas
Authors: Iachan Ronaldo , Berman Lewis , Kyle Tonja M. , Martin Kelly J. , Deng Yangyang , Moyse Davia N. , Middleton Deirdre , Atienza Audie A. 
Published: January 2019

Abstract

Background:
The Population Health Assessment initiative by NCI sought to enhance cancer centers’ capacity to acquire, aggregate, and integrate data from multiple sources, as well as to plan, coordinate, and enhance catchment area analysis activities.

Methods:
Key objectives of this initiative are pooling data and comparing local data with national data. A novel aspect of analyzing data from this initiative is the methodology used to weight datasets from sites that collected both probability and nonprobability samples. This article describes the methods developed to weight data, which cancer centers collected with combinations of probability, and nonprobability sampling designs.

Results:
We compare alternative weighting methods in particular for the hybrid probability and nonprobability sampling designs employed by different cancer centers. We also include comparisons of local center data with national survey data from large probability samples.

Conclusions:
This hybrid approach to calculating statistical weights can be implemented both within cancer centers that collect both probability and nonprobability samples with common measures. Aggregation can also apply to cancer centers that share common data elements, and target similar populations, but differ in survey sampling designs.

Impact:
Researchers interested in local versus national comparisons for cancer surveillance and control outcomes should consider various weighting approaches, including hybrid approaches, when analyzing their data.
Autophagy Inhibition to Augment mTOR Inhibition: a Phase I/II Trial of Everolimus and Hydroxychloroquine in Patients with Previously Treated Renal Cell Carcinoma
Authors: Haas Naomi B. , Appleman Leonard J. , Stein Mark , Redlinger Maryann , Wilks Melissa , Xu Xiaowei , Onorati Angelique , Kalavacharla Anusha , Kim Taehyong , Zhen Chao Jie , Kadri Sabah , Segal Jeremy P. , Gimotty Phyllis A. , Davis Lisa E. , Amaravadi Ravi K. 
Published: January 2019

Abstract

Purpose:
Everolimus inhibits the mTOR, activating cytoprotective autophagy. Hydroxychloroquine inhibits autophagy. On the basis of preclinical data demonstrating synergistic cytotoxicity when mTOR inhibitors are combined with an autophagy inhibitor, we launched a clinical trial of combined everolimus and hydroxychloroquine, to determine its safety and activity in patients with clear-cell renal cell carcinoma (ccRCC).

Patients and Methods:
Three centers conducted a phase I/II trial of everolimus 10 mg daily and hydroxychloroquine in patients with advanced ccRCC. The objectives were to determine the MTD of hydroxychloroquine with daily everolimus, and to estimate the rate of 6-month progression-free survival (PFS) in patients with ccRCC receiving everolimus/hydroxychloroquine after 1–3 prior treatment regimens. Correlative studies to identify patient subpopulations that achieved the most benefit included population pharmacokinetics, measurement of autophagosomes by electron microscopy, and next-generation tumor sequencing.

Results:
No dose-limiting toxicity was observed in the phase I trial. The recommended phase II dose of hydroxychloroquine 600 mg twice daily with everolimus was identified. Disease control [stable disease + partial response (PR)] occurred in 22 of 33 (67%) evaluable patients. PR was observed in 2 of 33 patients (6%). PFS ≥ 6 months was achieved in 15 of 33 (45%) of patients who achieved disease control.

Conclusions:
Combined hydroxychloroquine 600 mg twice daily with 10 mg daily everolimus was tolerable. The primary endpoint of &gt;40% 6-month PFS rate was met. Hydroxychloroquine is a tolerable autophagy inhibitor in future RCC or other trials.
Vaccine-Induced Memory CD8+ T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study
Authors: Crosby Erika J. , Gwin William , Blackwell Kimberly , Marcom Paul K. , Chang Serena , Maecker Holden T. , Broadwater Gloria , Hyslop Terry , Kim Sungjin , Rogatko Andre , Lubkov Veronica , Snyder Joshua C. , Osada Takuya , Hobeika Amy C. , Morse Michael A. , Lyerly H. Kim , Hartman Zachary C. 
Published: January 2019

AbstractPurpose:Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T-cell infiltration of tumors include vaccines targeting established oncogenic drivers such as the genomic amplification of HER2. We constructed a vaccine based on a novel alphaviral vector encoding a portion of HER2 (VRP-HER2).Patients and Methods:In preclinical studies, mice were immunized with VRP-HER2 before or after implantation of hHER2+ tumor cells and HER2-specific immune responses and antitumor function were evaluated. We tested VRP-HER2 in a phase I clinical trial where subjects with advanced HER2-overexpressing malignancies in cohort 1 received VRP-HER2 every 2 weeks for a total of 3 doses. In cohort 2, subjects received the same schedule concurrently with a HER2-targeted therapy.Results:Vaccination in preclinical models with VRP-HER2 induced HER2-specific T cells and antibodies while inhibiting tumor growth. VRP-HER2 was well tolerated in patients and vaccination induced HER2-specific T cells and antibodies. Although a phase I study, there was 1 partial response and 2 patients with continued stable disease. Median OS was 50.2 months in cohort 1 (n = 4) and 32.7 months in cohort 2 (n = 18). Perforin expression by memory CD8 T cells post-vaccination significantly correlated with improved PFS.Conclusions:VRP-HER2 increased HER2-specific memory CD8 T cells and had antitumor effects in preclinical and clinical studies. The expansion of HER2-specific memory CD8 T cells in vaccinated patients was significantly correlated with increased PFS. Subsequent studies will seek to enhance T-cell activity by combining with anti-PD-1.
Anatomical Connections Between the Papillary Muscles and the Ventricular Myocardium
Authors: Rivera Santiago , Vecchio Nicolás , Ricapito Paz 
Published: January 2019

Background:
Papillary muscles (PM) ventricular arrhythmias (VAs) exhibit QRS variability, attributed to anisotropy. ECG inconsistencies such as late precordial transition (TZ) and discordant QRS axis may not be solely explained by anisotropic conduction. We sought to determine the presence of anatomic connections of the PM and correlate them with ECG inconsistencies and ablation results.

Methods:
Patients with prior PM VAs catheter ablation (N=33/66 PMs) were prospectively evaluated with cardiac resonance for the presence of muscular connection (PMCs) away from the PM base. Specific ECG characteristics including early (consistent TZ) and late (inconsistent-ITZ) TZ or inconsistent (IQA) or consistent QA QRS axis were correlated with PMCs.

Results:

Thirty-five PMs exhibited clinical VAs (N=29 posteromedial PM and N=6 anterolateral PM). PM VAs with ITZ and IQA were observed in 11 and 9 PMs, respectively. In total, 41 PMs (62%) exhibited 90 PMCs. Arrhythmogenic PMs (N=35) exhibited higher number of PMCs (72 versus 18;
P
=0.01). Patients with ITZ and IQA exhibited 100% prevalence of PMCs. Those with consistent TZ and consistent QA showed 40% and 26% prevalence of PMCs, respectively. ITZ and IQA predicted the presence of PMCs with 59% of 28% sensitivity; and 100% of 100% specificity, respectively. Type-specific PMCs were more prevalent in patients with ECG inconsistencies. Those PMs are exhibiting clinical recurrence after ablation presented higher prevalence of PMCs (91% versus 60%;
P
=0.04).

Conclusions:
PMCs are highly prevalent in patients with PM VAs. A direct correlation exists between PM VAs ECG inconsistencies and type-specific PMCs. Patients with ITZ or IQA exhibited PMC 100% prevalence. Recurrence was higher among patients with PMCs.
Characteristics of Acute Heart Failure Hospitalizations Based on Presenting Severity
Authors: Parikh Kishan S. , Sheng Shubin , Hammill Bradley G. , Yancy Clyde W. , Fonarow Gregg C. , Hernandez Adrian F. , DeVore Adam D. 
Published: January 2019

Background:
Hospitalizations for acute heart failure (HF) are significant events with downstream implications for patients, as well as healthcare systems and payers. However, from anecdotal experience, both hospitalization and postdischarge courses vary significantly based on severity of presenting decompensation.

Methods and Results:
We compared patient and hospitalization characteristics, resource utilization, and associated outcomes, among modern era acute HF patients enrolled in the GWTG–HF (Get With the Guidelines–Heart Failure) registry between 2011 and 2016, by varying severity of their acute HF. Among over 165 000 hospitalizations included in our analysis, 2% were considered high-risk and 32% intermediate-risk for in-hospital mortality, similar to findings from 15 years prior. Further, the 1-year mortality rate was 40% among Medicare beneficiaries in GWTG–HF who survived to hospital discharge.

Conclusions:
The long-term outcomes among acute HF survivors remain poor and, in the context of an increasing HF burden, warrant further study of postdischarge management strategies including inpatient-to-clinic transitions and ambulatory HF systems-based care.
Description of the Southern swamp leech Philobdella floridana (Verrill, 1874) (Annelida: Hirudinea) from the Outer Banks, North Carolina, USA, with a revision of the species
Authors: SAWYER ROY T. 
Published: January 2019

The jawed leech Philobdella floridana (Verrill, 1874) occurs widely in swamps of the southeastern United States. The discovery of a population of P. floridana in Lake Phelps, an isolated lake in the Albemarle Peninsula in the Outer Banks region of North Carolina, is by far the northernmost record for this species. Description of the Lake Phelps leech in this paper is the first comprehensive account of the internal anatomy of P. floridana. Comparable internal descriptions of P. floridana from other geographic regions are also presented for the first time. This new understanding of the internal features of this species is the basis of a taxonomic revision of P. floridana. All specimens examined in this study possessed remarkably similar jaws and teeth within the range of 22–26 per jaw, regardless of the size or origin of the leech. All mature specimens possessed external copulatory slits and pores which uniquely characterise the genus Philobdella. This study shows for the first time that these external features are attributable to a complex internal network of gastropores emanating from the crop caeca of the genital segments. Nonetheless, the reproductive anatomy of this species is by far the most rudimentary of any Hirudinidae in North America. A major finding of this study is that the Lake Phelps population differs significantly from other known P. floridana in one significant respect. Specifically, the gut has an intimate anatomical association with the nephridia, an enteronephric feature previously unknown within the Hirudinea. At least in this study, enteronephry may be confined to Lake Phelps, leaving open the possibility that this population of P. floridana may be endemic to this relict lake which has a history of endemicity.
Tenoxicam IV in Major Gynaecological Surgery— Pharmacokinetic, Pain Relief and Haematological Effects
Authors: Jones R. D. M. , Miles W. , Prankerd R. , Lang C. , Chilvers M. , Lo S. K. 
Published: January 2019

This study compared postoperative analgesic dispensation and measures relating to haemostasis following intravenous administration, in a randomized double-blinded manner, of either placebo or tenoxicam 20 mg to 30 women presenting for major gynaecological oncology surgery under a standardized, combined epidural/general anaesthetic technique. Pharmacokinetic disposition of tenoxicam in this patient cohort was also described. There was no objective or subjective alteration in haemostatic function or increase in blood loss, nor any deviation from the normal range of values. Postoperative analgesia during the first 48 hours was delivered to achieve a VAS endpoint of less than five on leg-raising, by a combination of a nurse-controlled low-dose background epidural infusion and patient-administered epidural bolus. Greater VAS variability was observed during the first four postoperative hours (P=0.08). The tenoxicam group self-administered significantly fewer epidural bolus doses to maintain satisfactory analgesia compared with the placebo group during the first 24 hours (P=0.004) and 48 hours (P=0.01) post-operatively. Similar differences between the groups in the total dose of the epidural bupivacaine/fentanyl mixture delivered were described (4 h: P=0.148; 24h: P=0.033; 48 h: P=0.001) (Figure 2). Despite surgery, transfusion and the use of a renal protective fluid administration strategy, tenoxicam disposition was not greatly different from that widely described for healthy volunteers. There were no significant side-effects and no adverse events attributable to tenoxicam. In this small study we have shown that tenoxicam administered preoperatively reduced the epidural analgesic requirements during the first 48 hours following major gynaecological surgery. There was no clinical or pathological evidence of haematological impairment following a single IV administration of tenoxicam 20 mg.
The Effect of Adding Fentanyl to Ropivacaine 0.125% on Patient-Controlled Epidural Analgesia during Labour
Authors: Ruban P. , Sia A. T. H. , Chong J. L. 
Published: January 2019

The use of patient-controlled epidural analgesia (PCEA) for labour analgesia is rapidly gaining acceptance. However, the ideal PCEA solution and PCEA program remains uncertain. We studied the effect of adding fentanyl 2 μg/ml on demand-only PCEA using ropivacaine 0.125% for labour analgesia. With the approval of the Hospital Ethics Committee, this prospective randomized controlled trial was conducted on 36 nulliparous ASA 1/2 parturients in early, but established, labour. Upon written consent, epidural analgesia was started with 10 ml ropivacaine 0.2%. The parturients subsequently were randomized to receive either ropivacaine 0.125% (n=18) or ropivacaine 0.125% with fentanyl 2 μg/ml (n=18). The PCEA was programmed to a demand-only mode with bolus of 5 ml, lockout time of 10 minutes and maximum volume per hour of 20 ml. The degree of pain relief was similar in both groups. However, the total amount of ropivacaine used per hour was lower in the group that received fentanyl (median 7.1 vs 10.1 mg, P<0.05). This was not associated with a decrease in motor blockade or a decrease in instrumental deliveries. The ratio of successful PCEA demand to total number of demands, the satisfaction score and the maternal-fetal outcome were similar in both groups. In conclusion, the addition of fentanyl had a dose-sparing effect on the requirement of ropivacaine. This PCEA regimen produced a low incidence of motor block, good labour pain relief and excellent patient satisfaction.
Fire during Thoracic Surgery
Authors: Lai A. , Ng K. P. 
Published: January 2019

A 67-year-old male with bilateral lung lesions presented for median sternotomy. One-lung ventilation was complicated by arterial desaturation. Continuous positive airway pressure with oxygen was applied to the non-ventilated lung to relieve the hypoxaemia. However, the cotton gauze packed inside the operative site was ignited by the electrocautery. The burning gauze was immediately removed without any complication. We report a case of electrocautery-induced fire during thoracic surgery done in supine position and discuss its implication on the choice of oxygen enrichment therapy during one-lung ventilation.