bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structure of human IRAK1
Authors: Wang Li , Qiao Qi , Ferrao Ryan , Shen Chen , Hatcher John M. , Buhrlage Sara J. , Gray Nathanael S. , Wu Hao
Published: December 2017

Significance

Innate immune signaling has an essential role in inflammation, and dysfunction of signaling components in these pathways contributes to autoimmunity and cancer. Interleukin-1 receptor-associated kinase (IRAK) family members are key mediators of signal transduction by Toll-like receptors and Interleukin-1 receptors in innate immunity and therefore serve as potential therapeutic targets for these diseases. The crystal structure of the IRAK1 kinase domain in complex with a small molecule inhibitor reveals important structural details of the kinase that provide insights into the design of selective IRAK inhibitors. Characterization of IRAK1 heterodimerization with the upstream kinase IRAK4 suggests a mechanism of IRAK1 activation by IRAK4.
Molecular basis for the recognition of the human AAUAAA polyadenylation signal
Authors: Sun Yadong , Zhang Yixiao , Hamilton Keith , Manley James L. , Shi Yongsheng , Walz Thomas , Tong Liang
Published: December 2017

Nearly all eukaryotic messenger RNA precursors must undergo cleavage and polyadenylation at their 3′-end for maturation. A crucial step in this process is the recognition of the AAUAAA polyadenylation signal (PAS), and the molecular mechanism of this recognition has been a long-standing problem. Here, we report the cryo-electron microscopy structure of a quaternary complex of human CPSF-160, WDR33, CPSF-30, and an AAUAAA RNA at 3.4-Å resolution. Strikingly, the AAUAAA PAS assumes an unusual conformation that allows this short motif to be bound directly by both CPSF-30 and WDR33. The A1 and A2 bases are recognized specifically by zinc finger 2 (ZF2) of CPSF-30 and the A4 and A5 bases by ZF3. Interestingly, the U3 and A6 bases form an intramolecular Hoogsteen base pair and directly contact WDR33. CPSF-160 functions as an essential scaffold and preorganizes CPSF-30 and WDR33 for high-affinity binding to AAUAAA. Our findings provide an elegant molecular explanation for how PAS sequences are recognized for mRNA 3′-end formation.
The role and significance of traditional leadership in the governance of modern democratic South Africa
Authors: Koenane Mojalefa Lehlohonolo J.
Published: December 2017

The institution of traditional leadership in Africa pre-existed both the colonial and apartheid systems and was the only known system of governance among indigenous people. However, contrary to the current political trend of discrediting traditional leadership, Africans have their own understanding of democracy, which is sharply from the liberal democracy of the west. The institution of traditional rulership was democratic in its own unique way in what we nowadays refer to as ‘consensus’. This article argues that the institution of traditional/indigenous leadership is still relevant as a trusted institution for governance by the majority of people living in rural South Africa. The Basotho adage: mooa khotla ha a tsekisoe is the maxim in which my argument – that traditional rulership is a sine qua non in rural areas – is grounded. The South African democratic government has failed to decisively define and unambiguously clarify the role of traditional leadership in government. The article aims to demonstrate government’s strategy of rendering the institution of traditional leadership obsolete and thus erasing it from South African political landscape. The debate on the role of traditional leadership is mainly founded on two diverse viewpoints: traditionalism and modernism; these viewpoints will form part of this paper. In this paper, I will refer to the legal or political framework of South Africa on the institution of traditional leadership.
Short Aβ peptides attenuate Aβ42 toxicity in vivo
Authors: Moore Brenda D. , Martin Jason , de Mena Lorena , Sanchez Jonatan , Cruz Pedro E. , Ceballos-Diaz Carolina , Ladd Thomas B. , Ran Yong , Levites Yona , Kukar Thomas L. , Kurian Justin J. , McKenna Robert , Koo Edward H. , Borchelt David R. , Janus Christopher , Rincon-Limas Diego , Fernandez-Funez Pedro , Golde Todd E.
Published: December 2017

Processing of amyloid-β (Aβ) precursor protein (APP) by γ-secretase produces multiple species of Aβ: Aβ40, short Aβ peptides (Aβ37–39), and longer Aβ peptides (Aβ42–43). γ-Secretase modulators, a class of Alzheimer’s disease therapeutics, reduce production of the pathogenic Aβ42 but increase the relative abundance of short Aβ peptides. To evaluate the pathological relevance of these peptides, we expressed Aβ36–40 and Aβ42–43 in Drosophila melanogaster to evaluate inherent toxicity and potential modulatory effects on Aβ42 toxicity. In contrast to Aβ42, the short Aβ peptides were not toxic and, when coexpressed with Aβ42, were protective in a dose-dependent fashion. In parallel, we explored the effects of recombinant adeno-associated virus–mediated expression of Aβ38 and Aβ40 in mice. When expressed in nontransgenic mice at levels sufficient to drive Aβ42 deposition, Aβ38 and Aβ40 did not deposit or cause behavioral alterations. These studies indicate that treatments that lower Aβ42 by raising the levels of short Aβ peptides could attenuate the toxic effects of Aβ42.
Molecular moieties masking Ca2+-dependent facilitation of voltage-gated Cav2.2 Ca2+ channels
Authors: Thomas Jessica R. , Hagen Jussara , Soh Daniel , Lee Amy
Published: December 2017

Voltage-gated Cav2.1 (P/Q-type) Ca2+ channels undergo Ca2+-dependent inactivation (CDI) and facilitation (CDF), both of which contribute to short-term synaptic plasticity. Both CDI and CDF are mediated by calmodulin (CaM) binding to sites in the C-terminal domain of the Cav2.1 α1 subunit, most notably to a consensus CaM-binding IQ-like (IQ) domain. Closely related Cav2.2 (N-type) channels display CDI but not CDF, despite overall conservation of the IQ and additional sites (pre-IQ, EF-hand–like [EF] domain, and CaM-binding domain) that regulate CDF of Cav2.1. Here we investigate the molecular determinants that prevent Cav2.2 channels from undergoing CDF. Although alternative splicing of C-terminal exons regulates CDF of Cav2.1, the splicing of analogous exons in Cav2.2 does not reveal CDF. Transfer of sequences encoding the Cav2.1 EF, pre-IQ, and IQ together (EF-pre-IQ-IQ), but not individually, are sufficient to support CDF in chimeric Cav2.2 channels; Cav2.1 chimeras containing the corresponding domains of Cav2.2, either alone or together, fail to undergo CDF. In contrast to the weak binding of CaM to just the pre-IQ and IQ of Cav2.2, CaM binds to the EF-pre-IQ-IQ of Cav2.2 as well as to the corresponding domains of Cav2.1. Therefore, the lack of CDF in Cav2.2 likely arises from an inability of its EF-pre-IQ-IQ to transduce the effects of CaM rather than weak binding to CaM per se. Our results reveal a functional divergence in the CDF regulatory domains of Cav2 channels, which may help to diversify the modes by which Cav2.1 and Cav2.2 can modify synaptic transmission.
Drug knowledge bases and their applications in biomedical informatics research
Authors: Zhu Yongjun , Elemento Olivier , Pathak Jyotishman , Wang Fei
Published: December 2017

Recent advances in biomedical research have generated a large volume of drug-related data. To effectively handle this flood of data, many initiatives have been taken to help researchers make good use of them. As the results of these initiatives, many drug knowledge bases have been constructed. They range from simple ones with specific focuses to comprehensive ones that contain information on almost every aspect of a drug. These curated drug knowledge bases have made significant contributions to the development of efficient and effective health information technologies for better health-care service delivery. Understanding and comparing existing drug knowledge bases and how they are applied in various biomedical studies will help us recognize the state of the art and design better knowledge bases in the future. In addition, researchers can get insights on novel applications of the drug knowledge bases through a review of successful use cases. In this study, we provide a review of existing popular drug knowledge bases and their applications in drug-related studies. We discuss challenges in constructing and using drug knowledge bases as well as future research directions toward a better ecosystem of drug knowledge bases.
Outcome Measures Used in Pulmonary Rehabilitation in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review
Authors: Oliveira Ana L , Marques Alda S
Published: December 2017

Background

Conflicting results about the effects of community-based pulmonary rehabilitation in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) exist, possibly because the variety of outcome measures used and the lack of appropriate measurement properties hinder the development of pulmonary rehabilitation guidelines.

Purpose

The purpose of this study was to identify and review the measurement properties of patient-reported outcome measures (PROMs) and clinical outcome measures of AECOPD that are used in pulmonary rehabilitation and that can be easily applied in a community setting.

Data Sources

PubMed, Web of Science, Scopus, and CINAHL were searched up to July 1, 2016.

Study Selection

Phase 1 identified outcome measures used in pulmonary rehabilitation for AECOPD. Phase 2 reviewed the measurement properties of the identified outcome measures.

Data Extraction

One reviewer extracted the data and 2 reviewers independently assessed the methodological quality of the studies and the measurement properties of the outcome measures by using the Consensus-Based Standards for the Selection of Health Status Measurement Instruments (COSMIN) recommendations.

Data Synthesis

Twenty-three PROMs and 18 clinical outcome measures were found. The outcome measures most used were the St George Respiratory Questionnaire (n = 15/37 studies) and the 6-minute walk test (n = 21/37 studies). Thirty-two studies described the measurement properties of 22 PROMs and 7 clinical outcome measures. The methodological quality of the studies was mostly poor, and the measurement properties were mostly indeterminate. The outcome measure exhibiting more robust properties was the COPD Assessment Test.

Limitations

A number of studies were not found with the validated search strategy used and were included a posteriori; the fact that 3 studies presented combined results— for patients who were stable and patients with exacerbation—affected the conclusions that can be drawn.

Conclusions

A large variety of outcome measures have been used; however, studies on their measurement properties are needed to enhance the understanding of community pulmonary rehabilitation for AECOPD.
Ribotypes of Polymyxa graminis in Wheat Samples Infected with Soilborne Wheat Viruses in China
Authors: Xu Yu , Hu Lifeng , Li Linying , Zhang Yan , Sun Bingjian , Meng Xiangfeng , Zhu Tongquan , Sun Zongtao , Hong Gaojie , Chen Yang , Yan Fei , Yang Jian , Li Junmin , Chen Jianping
Published: December 2017

Polymyxa graminis is an obligate parasite and important vector of more than 14 soilborne plant viruses that pose a significant threat to cereal crops in Europe, North America, and Asia. Different ribotypes or formae speciales of P. graminis have been recognized and these may be associated with different cereal hosts or with transmission of different viruses. Two soilborne viruses infecting winter wheat in China have been reported and well studied (Wheat yellow mosaic virus [WYMV, genus Bymovirus] and Chinese wheat mosaic virus [CWMV, genus Furovirus]) but there has been no reported characterization of P. graminis isolates associated with them. In this study, the ribosomal DNA internal transcribed spacer (ITS) regions of P. graminis were examined from 63 wheat samples with apparent virus symptoms obtained from 16 sites within six Chinese provinces. Their associations with soilborne viruses were investigated. Ribotype I (P. graminis f. sp. temperata) and ribotype II (P. graminis f. sp. tepida) were confirmed in winter wheat regions of China for the first time. All 63 wheat root samples were infected with ribotype I of P. graminis and 11 were also infected with ribotype II. There was no obvious association between the ribotypes and infection by either WYMV or CWMV (or double infection). Phylogenetic analysis of the P. graminis ITS1-5.8S-ITS2 sequences revealed that ribotype I in China belongs to previously reported subgroup Ib, whereas ribotype II belongs to IIa. There was considerable sequence variation (pairwise distances from 0.0219 to 0.0319) between Chinese ribotype I isolates of different regions and previously reported ribotype I isolate Ken5 (accession number HE860055.1).
The Use of Features from Fluorescence, Thermography, and NDVI Imaging to Detect Biotic Stress in Lettuce
Authors: Sandmann Martin , Grosch Rita , Graefe Jan
Published: December 2017

Fluorescence, normalized difference vegetation index, and thermal imaging are three frequently used nondestructive methods to detect biotic stress in plants. Due, in part, to the inconsistent results reported in the literature and the lack of measurements on the whole-plant scale, we tested the suitability of a wide variety of variables obtained using these three imaging methods to classify young plants into biotically stressed and nonstressed plants. To this end, we applied the model plant–pathogen system lettuce–Rhizoctonia solani. The relevant data from each image and plant (healthy and diseased) was extracted semiautomatically using sophisticated image processing algorithms. This method enabled us to identify the most appropriate variables via discriminant function and logistic regression analysis: photosystem II maximum quantum yield (Fv/Fm) and fluorescence decline ratio can be used to classify variables with an error ≤0.052. Lettuce seedlings with an Fv/Fm ratio > 0.73 were consistently healthy. In some cases, it was possible to detect infection prior to the appearance of symptoms. Possibilities to transfer the method to horticultural practice are discussed.
Pushing Critical Thinking Skills With Multiple-Choice Questions: Does Bloom’s Taxonomy Work?
Authors: Zaidi Nikki L. Bibler , Grob Karri L. , Monrad Seetha M. , Kurtz Joshua B. , Tai Andrew , Ahmed Asra Z. , Gruppen Larry D. , Santen Sally A.
Published: December 2017

Medical school assessments should foster the development of higher-order thinking skills to support clinical reasoning and a solid foundation of knowledge. Multiple-choice questions (MCQs) are commonly used to assess student learning, and well-written MCQs can support learner engagement in higher levels of cognitive reasoning such as application or synthesis of knowledge. Bloom’s taxonomy has been used to identify MCQs that assess students’ critical thinking skills, with evidence suggesting that higher-order MCQs support a deeper conceptual understanding of scientific process skills. Similarly, clinical practice also requires learners to develop higher-order thinking skills that include all of Bloom’s levels. Faculty question writers and examinees may approach the same material differently based on varying levels of knowledge and expertise, and these differences can influence the cognitive levels being measured by MCQs. Consequently, faculty question writers may perceive that certain MCQs require higher-order thinking skills to process the question, whereas examinees may only need to employ lower-order thinking skills to render a correct response. Likewise, seemingly lower-order questions may actually require higher-order thinking skills to respond correctly. In this Perspective, the authors describe some of the cognitive processes examinees use to respond to MCQs. The authors propose that various factors affect both the question writer and examinee’s interaction with test material and subsequent cognitive processes necessary to answer a question.
Why Open-Ended Survey Questions Are Unlikely to Support Rigorous Qualitative Insights
Authors: LaDonna Kori A. , Taylor Taryn , Lingard Lorelei
Published: December 2017

Health professions education researchers are increasingly relying on a combination of quantitative and qualitative research methods to explore complex questions in the field. This important and necessary development, however, creates new methodological challenges that can affect both the rigor of the research process and the quality of the findings. One example is “qualitatively” analyzing free-text responses to survey or assessment instrument questions. In this Invited Commentary, the authors explain why analysis of such responses rarely meets the bar for rigorous qualitative research. While the authors do not discount the potential for free-text responses to enhance quantitative findings or to inspire new research questions, they caution that these responses rarely produce data rich enough to generate robust, stand-alone insights. The authors consider exemplars from health professions education research and propose strategies for treating free-text responses appropriately.
Feasibility and Accuracy of Thoracolumbar Minimally Invasive Pedicle Screw Placement With Augmented Reality Navigation Technology
Authors: Elmi-Terander Adrian , Nachabe Rami , Skulason Halldor , Pedersen Kyrre , Söderman Michael , Racadio John , Babic Drazenko , Gerdhem Paul , Edström Erik
Published: December 2017

Study Design.

Cadaveric laboratory study.

Objective.

To assess the feasibility and accuracy of minimally invasive thoracolumbar pedicle screw placement using augmented reality (AR) surgical navigation.

Summary of Background Data.

Minimally invasive spine (MIS) surgery has increasingly become the method of choice for a wide variety of spine pathologies. Navigation technology based on AR has been shown to be feasible, accurate, and safe in open procedures. AR technology may also be used for MIS surgery.

Methods.

The AR surgical navigation was installed in a hybrid operating room (OR). The hybrid OR includes a surgical table, a motorized flat detector C-arm with intraoperative 2D/3D imaging capabilities, integrated optical cameras for AR navigation, and patient motion tracking using optical markers on the skin. Navigation and screw placement was without any x-ray guidance. Two neurosurgeons placed 66 Jamshidi needles (two cadavers) and 18 cannulated pedicle screws (one cadaver) in the thoracolumbar spine. Technical accuracy was evaluated by measuring the distance between the tip of the actual needle position and the corresponding planned path as well as the angles between the needle and the desired path. Time needed for navigation along the virtual planned path was measured. An independent reviewer assessed the postoperative scans for the pedicle screws’ clinical accuracy.

Results.

Navigation time per insertion was 90 ± 53 seconds with an accuracy of 2.2 ± 1.3 mm. Accuracy was not dependent on operator. There was no correlation between navigation time and accuracy. The mean error angle between the Jamshidi needles and planned paths was 0.9° ± 0.8°. No screw was misplaced outside the pedicle. Two screws breached 2 to 4 mm yielding an overall accuracy of 89% (16/18).

Conclusion.

MIS screw placement directed by AR with intraoperative 3D imaging in a hybrid OR is accurate and efficient, without any fluoroscopy or x-ray imaging during the procedure.

Level of Evidence: N/A
Postoperative Opioid Use, Complications, and Costs in Surgical Management of Lumbar Spondylolisthesis
Authors: Vail Daniel , Azad Tej D. , O’Connell Chloe , Han Summer S. , Veeravagu Anand , Ratliff John K.
Published: December 2017

Study Design.

Retrospective analysis on a national longitudinal database (2007–2014).

Objective.

To determine the association between arthrodesis and complication rates, costs, surgical revision, and postoperative opioid prescription.

Summary of Background Data.

Arthrodesis in patients receiving laminectomy for lumbar spondylolisthesis remains controversial. However, population-level evidence to support the use of arthrodesis remains limited.

Methods.

We identified 73,176 patient records and used coarsened exact matching to create comparable populations of patients who received laminectomy or laminectomy with arthrodesis. We use linear and logistic regression models to analyze the relationship between arthrodesis and postoperative complications, length of stay, costs, readmissions, surgical revisions, and postoperative opioid prescribing.

Results.

Patients who underwent arthrodesis spent 1 more day in the hospital on average (P < 0.01), and had higher costs of care at their index visit ($24,126, P < 0.01), which were partially offset by lower costs of care over the 2 years following their procedure ($14,667 less in arthrodesis patients, P = 0.01). Patients with arthrodesis were less likely to have a surgical revision (odds ratio = 0.66, P < 0.01). Patients with arthrodesis used more opioids in the first 2 months following their procedure, but had comparable opioid use to patients undergoing laminectomy without arthrodesis in all other postoperative months over the next 2 years, and were not more or less likely to convert to chronic opioid use. Postoperative opioid prescription varied dramatically across states (P < 0.01); geographic variation in opioid use is substantially greater than differences in opioid use based on procedure performed.

Conclusion.

Arthrodesis is associated with reduced likelihood of surgical revision and increased use of opioids in the first 2 months following surgery, but not associated with greater or lesser opioid use beyond the initial 2 postoperative months. Geographic variation in opioid use is substantial even after accounting for patient characteristics and for whether patients underwent arthrodesis.

Level of Evidence: 3
Sex Differences for Anterior Cervical Fusion
Authors: Basques Bryce A. , Hijji Fady Y. , Khechen Benjamin , Haws Brittany E. , Mayo Benjamin C. , Massel Dustin H. , Louie Philip K. , Cardinal Kaitlyn L. , Guntin Jordan A. , Singh Kern
Published: December 2017

Study Design.

Retrospective cohort.

Objective.

To assess differences in baseline characteristics between sexes of patients undergoing anterior cervical discectomy and fusion (ACDF) and risk factors for adverse outcomes according to sex.

Summary of Background Data.

ACDF is a common treatment for cervical spine disease. To reduce the rate of complications, risk factors associated with adverse events have been identified. However, few studies have examined the risk for inferior outcomes or complications after ACDF by sex.

Methods.

The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients who underwent ACDF from 2005 through 2014. Data collected included demographics, comorbidities, operative characteristics, and postoperative adverse events. Demographic and comorbidity variables were compared between men and women using chi-squared analysis. Perioperative outcomes were compared between groups using multivariate linear regression or Poisson regression with robust error variance controlling for preoperative characteristics.

Results.

In the 20,383 patients who met inclusion criteria, the male cohort was slightly older, less likely to be normal weight or morbidly obese, and had a higher incidence of diabetes and hypertension (P < 0.001 for each). Male sex was associated with a greater risk of any adverse event (relative risk = 1.2; P = 0.043), as well as any severe adverse event (relative risk  = 1.4; P = 0.001). Moreover, male sex exhibited longer operative times compared to the female group (127 vs. 117 min; β = 10; P < 0.001).

Conclusion.

The results of the current study suggest male sex is associated with an increased risk of adverse events following ACDF. Male sex has previously been demonstrated to correlate with medical comorbidities, which may be partly responsible for the increased morbidity. Because of the contrasting evidence throughout the literature, further studies are required to better elucidate this effect.

Level of Evidence: 3
PET-CT in Critically Ill Patients: Diagnosing the Unsuspected
Authors: Fort Romain , Ledochowski Stanislas , Friggeri Arnaud
Published: December 2017

Objective:

Quick identification of septic source is fundamental in patients with severe sepsis of unknown origin. The purpose of this case report was to assess the benefit and feasibility of an early PET-CT in critically ill patients with undiagnosed sepsis.

Data Sources:

Clinical observations of two patients.

Study Selection:

Case reports.

Data Extraction:

Data extracted from medical records, after patient’s consent. Illustrations were collected from the imaging software.

Data Synthesis:

We admitted two critically ill patients for suspected sepsis and altered mental state. As all bacteriological samples were initially sterile, diagnostic workups in both patients led us to suspect underlying malignant hemopathy. In fact, the lumbar puncture of the first patient revealed a large B-cell lymphoma, and an acquired thrombotic thrombocytopenic purpura was suspected in the second patient. However, PET-CTs performed in both patients displayed infra-clinical underlying infectious foci. Within 48 hours, both patients developed a clearly identified sepsis linked to the described focus, and favorable outcome thanks to the precious information delivered by the PET-CT.

Conclusions:

PET-CT precisely detected the deep foci of infection about 48 hours prior to the diagnosis of sepsis. The cases reports suggested the use of this image technique in ICU for patients with sepsis of unknown origin.
Prevention of Ventilator-Associated and Early Postoperative Pneumonia Through Tapered Endotracheal Tube Cuffs: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Maertens Bert , Blot Koen , Blot Stijn
Published: December 2017

Objective:

Microaspiration of subglottic secretions is considered a major pathogenic mechanism of hospital-acquired pneumonia, either early postoperative or ventilator-associated pneumonia. Tapered endotracheal tube cuffs have been proposed to provide a better seal of the extraluminal airway, thereby preventing microaspiration and possibly hospital-acquired pneumonia. We performed a systematic review and meta-analysis to assess the value of endotracheal tubes with tapered cuffs in the prevention of hospital-acquired pneumonia.

Data Sources:

A systematic search of MEDLINE, EMBASE, CENTRAL/CCTR, ClinicalTrials.gov, and ICTRP was conducted up to March 2017.

Study Selection:

Eligible trials were randomized controlled clinical trials comparing the impact of tapered cuffs versus standard cuffs on hospital-acquired pneumonia.

Data Extraction:

Random-effects meta-analysis calculated odds ratio and 95% CI for hospital-acquired pneumonia occurrence rate between groups. Secondary outcome measures included mortality, duration of mechanical ventilation, length of hospital and ICU stay, and cuff underinflation.

Data Synthesis:

Six randomized controlled clinical trials with 1,324 patients from intensive care and postoperative wards were included. Only two studies concomitantly applied subglottic secretion drainage, and no trial performed continuous cuff pressure monitoring. No significant difference in hospital-acquired pneumonia incidence per patient was found when tapered cuffs were compared with standard cuffs (odds ratio, 0.97; 95% CI, [0.73–1.28]; p = 0.81). There were likewise no differences in secondary outcomes.

Conclusions:

Application of tapered endotracheal tube cuffs did not reduce hospital-acquired pneumonia incidence among ICU and postoperative patients. Further research should examine the impact of concomitant use of tapered cuffs with continuous cuff pressure monitoring and subglottic secretion drainage.
Trends in Surgeon-Level Utilization of Sacral Nerve Stimulator Implantation for Fecal Incontinence in New York State
Authors: Xu Zhaomin , Fleming Fergal J. , Justiniano Carla F. , Becerra Adan Z. , Boodry Courtney I. , Aquina Christopher T. , Temple Larissa K. , Speranza Jenny R.
Published: December 2017

BACKGROUND:

There is a paucity of real-world data regarding surgeon utilization of sacral nerve stimulation for fecal incontinence compared with anal sphincteroplasty.

OBJECTIVE:

This study aims to examine trends in sacral nerve stimulation use compared with sphincteroplasty for fecal incontinence and surgeon-level variation in progression to implantation of the pulse generator.

DESIGN:

This is a population-based study.

PATIENTS:

Patients with fecal incontinence between 2011 and 2014 in New York who underwent stage 1 of the sacral nerve stimulation procedure were selected. For the comparison with sphincteroplasty, patients with fecal incontinence who underwent anal sphincteroplasty between 2008 and 2014 were included.

MAIN OUTCOME MEASURES:

The main outcomes after sacral nerve stimulation generator placement were unplanned 30-day admission, emergency department visit within 30 days, revision or explant of leads or generator, and 30-day mortality.

RESULTS:

Six hundred twenty-one patients with fecal incontinence underwent a stage 1 procedure with 79.7% progressing to stage 2. There has been an increase in the number of sacral nerve stimulation cases per year as well as the number of surgeons performing the procedure. The rate of progression to stage 2 among patients treated by colorectal surgeons was 80.2% compared with 77.0% among those treated by noncolorectal surgeons. Among those who completed stage 2, there were 3 (0.5%) unplanned 30-day admissions, 24 (4.4%) emergency department visits within 30 days, and 0 mortalities within 30 days. Thirty-two (6.5%) patients had their leads or pulse generator revised or explanted. There was a significant decrease in annual sphincteroplasty cases and the number of providers performing the procedure starting in 2011.

LIMITATIONS:

We lacked data regarding patient and physician decision making and the severity of disease.

CONCLUSIONS:

Sacral nerve stimulation for fecal incontinence is increasing in popularity with an increasing number of surgeons utilizing sacral nerve stimulation for fecal incontinence rather than sphincteroplasty. See Video Abstract at http://links.lww.com/DCR/A450.
Tranexamic Acid for Lower GI Hemorrhage: A Randomized Placebo-Controlled Clinical Trial
Authors: Smith Stephen R. , Murray David , Pockney Peter G. , Bendinelli Cino , Draganic Brian D. , Carroll Rosemary
Published: December 2017

BACKGROUND:

Lower GI hemorrhage is a common source of morbidity and mortality. Tranexamic acid is an antifibrinolytic that has been shown to reduce blood loss in a variety of clinical conditions. Information regarding the use of tranexamic acid in treating lower GI hemorrhage is lacking.

OBJECTIVE:

The aim of this trial was to determine the clinical efficacy of tranexamic acid when used for lower GI hemorrhage.

DESIGN:

This was a prospective, double-blind, placebo-controlled, randomized clinical trial.

SETTINGS:

The study was conducted at a tertiary referral university hospital in Australia.

PATIENTS:

Consecutive patients aged >18 years with lower GI hemorrhage requiring hospital admission from November 2011 to January 2014 were screened for trial eligibility (N = 265).

INTERVENTIONS:

A total of 100 patients were recruited after exclusions and were randomly assigned 1:1 to either tranexamic acid or placebo.

MAIN OUTCOME MEASURES:

The primary outcome was blood loss as determined by reduction in hemoglobin levels. The secondary outcomes were transfusion rates, transfusion volume, intervention rates for bleeding, length of hospital stay, readmission, and complication rates.

RESULTS:

There was no difference between groups with respect to hemoglobin drop (11 g/L of tranexamic acid vs 13 g/L of placebo; p = 0.9445). There was no difference with respect to transfusion rates (14/49 tranexamic acid vs 16/47 placebo; p = 0.661), mean transfusion volume (1.27 vs 1.93 units; p = 0.355), intervention rates (7/49 vs 13/47; p = 0.134), length of hospital stay (4.67 vs 4.74 d; p = 0.934), readmission, or complication rates. No complications occurred as a direct result of tranexamic acid use.

LIMITATIONS:

A larger multicenter trial may be required to determine whether there are more subtle advantages with tranexamic acid use in some of the secondary outcomes.

CONCLUSIONS:

Tranexamic acid does not appear to decrease blood loss or improve clinical outcomes in patients presenting with lower GI hemorrhage in the context of this trial. see Video Abstract at http://links.lww.com/DCR/A453.
Optimal Surveillance Protocols After Curative Resection in Patients With Stage IV Colorectal Cancer: A Multicenter Retrospective Study
Authors: Kishiki Tomokazu , Lapin Brittany , Matsuoka Hiroyoshi , Watanabe Takeshi , Takayasu Kohei , Kojima Koichiro , Sugihara Kenichi , Masaki Tadahiko
Published: December 2017

BACKGROUND:

After patients with stage IV colorectal cancer undergo curative surgical resection, there is a large risk for recurrence. To establish optimal surveillance guidelines, an understanding of the temporal risk factors for recurrence is necessary.

OBJECTIVE:

The primary aim of our study was to determine predictors for early (within 1 year), middle (1–2 years), and late (2 years or later) recurrence following curative resection in patients with stage IV colorectal cancer.

DESIGN:

This was a retrospective cohort study.

SETTINGS:

The study was conducted at multiple institutions.

PATIENTS:

The retrospective cohort study comprised 1070 patients with stage IV colorectal cancer after an R0 resection for the primary and metastatic lesions in 19 institutions from January 1997 to December 2007.

MAIN OUTCOME MEASURES:

Risk factors for early, middle, and late recurrence were determined by logistic regression and Cox proportional hazards models.

RESULTS:

The overall recurrence rate was 73% (784/1070). Cancer-specific survival was 29.5 months, and recurrence-free survival was 8.9 months. Early recurrence occurred in 488 (62%), middle recurrence in 184 (24%), and late recurrence in 112 (14%). In multivariable analysis, early recurrence risk factors included rectum site, depth of tumor invasion (T4), increasing N-staging, venous invasion, and liver metastasis. Late recurrence risk factors were tumor size ≤50 mm, and peritoneal dissemination.

LIMITATIONS:

Because of the retrospective nature of this study, postoperative therapy was not standardized.

CONCLUSIONS:

Risk factors differ for early, middle, and late recurrences of stage IV colorectal cancer following curative resection. Early (within 1 year) recurrence factors were rectum site, T4, N-staging, venous invasion, and liver metastasis, whereas late (2 years or later) recurrence risk factors were small tumor size and peritoneal dissemination. Our study provides important data to guide a surveillance protocol following stage IV colorectal cancer curative resection. See Video Abstract at http://links.lww.com/DCR/A460.
The cross-sectional association between chemerin and bone health in peri/pre and postmenopausal women: results from the EPIC-Potsdam study
Authors: Menzel Juliane , Biemann Ronald , Aleksandrova Krasimira , Schulze Matthias B. , Boeing Heiner , Isermann Berend , Weikert Cornelia
Published: December 2017

Objective:

Recent in vitro data suggested that the novel adipokine chemerin may influence bone health. However, only limited evidence of the relationship between chemerin and bone health in humans is available. Therefore, this study aimed to investigate the association between chemerin and broadband ultrasound attenuation (BUA) in peri/premenopausal and postmenopausal women.

Methods:

Data from the German population-based European Prospective Investigation into Cancer and Nutrition-Potsdam cohort comprising 404 peri/premenopausal and 279 postmenopausal women were analyzed. Multivariable-adjusted analysis of covariance including age, body mass index, waist circumference, smoking status, education, physical activity, alcohol consumption, and hormone use was used to investigate potential relationships between the adipokine and BUA levels in peri/premenopausal and postmenopausal women, respectively.

Results:

The concentrations of chemerin were lower in peri/premenopausal women (median 118.0 ng/mL, interquartile range [IQR] 99.2-135.0), compared with postmenopausal women (median 140.0 ng/mL, IQR 121.0-167.0). In peri/premenopausal women chemerin was inversely associated with BUA levels; after multivariable adjustment, a 10% increase in the chemerin concentration was significantly associated with 0.83 dB/MHz lower BUA levels (P = 0.0006). In postmenopausal women chemerin was not related to BUA levels (P = 0.8).

Conclusion:

The present study provides evidence for an inverse association between chemerin and BUA in peri/premenopausal women. Therefore, the study suggests that high chemerin concentrations may minimize peak bone mass and thereby may promote age-related bone loss. Further studies are needed to investigate the role of chemerin in bone homeostasis in peri/premenopausal and postmenopausal women.
Novel Pressure-Sensing Smart Insole System Used for the Prevention of Pressure Ulceration in the Insensate Foot
Authors: Alfonso Allyson R. , Rao Smita , Everett Breanne , Chiu Ernest S.
Published: December 2017

Wounds of the foot challenge reconstructive surgeons to manage multiple factors: sensibility, stability, and durability. In this article, we focus on the insensate foot, which poses challenges to wound prevention with its propensity to develop pressure ulceration. The authors present the innovative use of a pressure-sensing smart insole system (SurroSense Rx, Orpyx Medical Technologies Inc., Calgary, Canada) in the management of the insensate foot in a patient following foot reconstruction. The pressure-sensing smart insole system provided unique feedback to both patient and provider in ways that contributed to the prevention of pressure ulcer recurrence, as well as highlight the importance of prescribed footwear in both the affected and unaffected foot. Wearable real-time monitoring and feedback faces the challenge of patient adherence. Future studies are indicated to examine the specific behaviors that are associated with favorable outcomes and long-term behavior changes.
Trends in Urodynamic Procedures, Surgical Procedures, and Overall Health Resource Utilization in the Adult Taiwanese Population With Urinary Incontinence: A Secondary Data Analysis
Authors: HSU Lan-Fang , CHANG Ling-Yin , LIAO Yuan-Mei , YEH Shauh-Der , TSAI Pei-Shan
Published: December 2017

Background:

The prevalence and incidence of the main risk factors for urinary incontinence (UI) have both increased over time. In addition, official statistics indicate that Taiwan is on course to evolve from an aging society into an aged society within the next decade. However, most of the studies in the literature that address the natural history of UI target Western and other non-Asian populations. Taiwan lacks knowledge of the natural history of UI.

Purpose:

The aims of this research were to study the trends in the use of urodynamic and surgical procedures for various subtypes of UI and to investigate the relationship between UI and healthcare resource utilization.

Methods:

The data on 1 million, randomly selected people who were enrolled in the Taiwan National Health Insurance program between 2000 and 2008 were extracted from the Longitudinal Health Insurance Database. The population and all procedures were identified based on the International Classification of Disease, Ninth Revision, Clinical Modification codes. Annual incidence of UI was calculated on an annual basis, and trend analysis was performed using logistic regression models. The association between UI and healthcare utilization was examined using generalized linear models in a gamma distribution with a log link function.

Results:

Overall, the trend in the annual incidence for all types of UI increased significantly (p < .01). Significantly increasing trends in the use of urodynamic procedures over time were observed for mixed and other types of UI (p < .01). In addition, a significantly increasing trend was observed in the annual rates of surgical procedures that were received by patients with urge or stress UI (p < .05). Patients with UI showed significantly higher healthcare resource utilization, including number of ambulatory visits, number of hospitalizations, average ambulatory care expenditures, and average days of hospitalization, than those without UI. However, limited information is available on the conservative treatment of UI in the database.

Conclusions:

UI symptoms may lead to increased healthcare resource utilization in patients with UI.
The Effects of Sleep on the Commensal Microbiota
Authors: Parekh Parth J. , Oldfield Edward C. , Johnson David A.
Published: December 2017

Sleep dysfunction is an epidemic, the implications of which have a profound impact on a variety of gastrointestinal disease. Recent data suggests a relationship between sleep dysfunction and intestinal dysbiosis, a known proinflammatory driver. This article evaluates the interplay between sleep dysfunction and gastrointestinal health and disease, with a focus on the impact of circadian rhythm disruption on the commensal microbiota.
The importance of the microbiome in pediatrics and pediatric infectious diseases
Authors: Gaufin Thaidra , Tobin Nicole H. , Aldrovandi Grace M.
Published: December 2017

Purpose of review

Emerging research on the pediatric microbiome implicates the importance of the microbiome on the development of the immune system, nervous system, and growth. Changes to the microbiome during infancy are associated with the development of chronic illnesses such as asthma and inflammatory bowel disease. Additionally, the microbiome provides protection against certain pathogens, affects vaccine responses, and alters drug metabolism. This review highlights what is known about the microbiome, the establishment of a healthy microbiome and the significance that changes to the microbiome composition have on growth and health of children and adolescents.

Recent findings

Vaginal delivery, breastfeeding, maternal health, and nutrition help shape a healthy microbiome. Caesarian delivery, formula feeding, and antibiotic use perturb the microbiome and are associated with the development of type II diabetes, asthma, allergic diseases, and obesity later in life. Specific interventions using pre and probiotics in multiple settings are under investigation with limited success.

A better understanding of the microbiome and the interaction with the immune system may help guide interventions to alter the microbiome toward a state of lifelong health.
Treatment Patterns and Clinical Outcomes in Patients With Metastatic Gastroenteropancreatic Neuroendocrine Tumors Treated in the Community Practice Setting in the United States
Authors: Jiao Xiaolong , Pulgar Sonia , Boyd Marley , Braiteh Fadi , Mirakhur Beloo , Pitman Lowenthal Susan , Fox Patricia , Frytak Jennifer , Cox David , Paulson A. Scott
Published: December 2017

Objective

This study was conducted to understand treatment patterns and clinical outcomes in metastatic gastroenteropancreatic neuroendocrine tumor patients treated in a large community oncology network.

Methods

This retrospective study used the McKesson Specialty Health/US Oncology Network iKnowMed electronic health record database with supplemental chart review. Eligibility criteria included a metastatic neuroendocrine tumor diagnosis between January 1, 2008, and to December 31, 2012; at least 2 US Oncology Network visits; and age at least 18 years. Follow-up was through October 31, 2014.

Results

Among the 229 patients identified, median age was 64.0 years, 52.4% were male, 69.4% were white, and 62.9% were overweight/obese. Primary tumor sites included small bowel (47.6%), pancreas (31.4%), and stomach/colorectum (21.0%). There were 16.2% under observation without treatment, 52.4% received only somatostatin analogs (SSAs), and 31.4% received chemotherapy/targeted therapy during treatment. In the first-line setting (n = 192), 77% received SSAs, 12% received chemotherapy, and 10.9% received targeted therapy. Fifty percent of patients receiving octreotide had a relative dose intensity of less than 85%, and 16.7% received above-label dose. Toxicities of SSAs included diarrhea (18.2%), abdominal pain (16.9%), and fatigue (13.5%). Median overall survival from diagnosis was 68.0 months (95% confidence interval, 57.1 to not reached).

Conclusions

Most metastatic gastroenteropancreatic neuroendocrine tumor patients received systemic treatment with SSAs. Patient treatment used an individualized dosing approach. Overall survival and toxicity were consistent with the published literature.
Biliary Stenting in Patients With Pancreatic Cancer
Authors: Payne Madeleine , Burmeister Elizabeth A. , Waterhouse Mary , Jordan Susan J. , O'Connell Dianne L. , Merrett Neil D. , Goldstein David , Wyld David , Beesley Vanessa L. , Gooden Helen , Janda Monika , Neale Rachel E.
Published: December 2017

Objective

We aimed to describe management of biliary obstruction (BO) in the context of pancreatic cancer within a population-based cohort.

Methods

We examined management of BO in 1863 patients diagnosed as having pancreatic cancer in 2010/2011. We used descriptive statistics and logistic regression to describe patterns of biliary stent usage, complications and duration of patency, associations between preoperative stenting and surgical outcomes, and between patient factors and management of jaundice.

Results

Almost half of the people in the cohort (n = 909) were jaundiced within 12 months of diagnosis. Two-thirds of these had at least 1 stent inserted. Preoperative stenting, mostly with plastic stents, occurred for 72% of patients who experienced jaundice prior to an attempted resection but was not associated with surgical outcomes. Seventy percent of the jaundiced patients who did not have an attempted resection were stented. Metal stents were less frequently replaced within 30 days than plastic (9% vs 42%). Living in a rural area was associated with reduced likelihood of having jaundice managed.

Conclusions

Plastic stents were still used frequently, despite guidelines recommending metal in most contexts. Patients living in rural areas were less likely to have BO managed. This work highlights the need to monitor current practice.
Cortisol Outperforms Novel Cardiovascular, Inflammatory, and Neurohumoral Biomarkers in the Prediction of Outcome in Acute Pancreatitis
Authors: Nebiker Christian A. , Staubli Sebastian , Schäfer Juliane , Bingisser Roland , Christ-Crain Mirjam , Dell-Kuster Salome , Mueller Christian , Scamardi Karla , Viehl Carsten T. , Kolleth Dieter , von Holzen Urs , Oertli Daniel , Rosenthal Rachel
Published: December 2017

Objectives

The aims of this study were to assess whether copeptin, pro–atrial natriuretic peptide, proadrenomedullin, and cortisol are associated with disease severity in patients with acute pancreatitis (AP) and to compare their ability in predicting organ failure or death.

Methods

From April 2011 to January 2015, 142 patients with AP were included in this prospective single-center study and observed for 4 days. Disease severity was rated by the Atlanta 1992 and 2012 criteria and organ failure by the modified Marshall score. The aforementioned laboratory markers, C-reactive protein, and procalcitonin were measured.

Results

Patients with moderate to severe AP showed significantly higher plasma concentrations of all biomarkers than did those with mild AP. Overall, 30 organ failures or deaths occurred. All biomarkers except cortisol had only modest discriminatory ability, with areas under the receiver operating characteristic curve (AUCs) between 0.44 and 0.66. Cortisol showed an AUC of 0.78 compared with the Acute Physiology and Chronic Health Evaluation II score with an AUC of 0.75.

Conclusions

Cortisol was the best predictor of organ failure or death. All biomarkers were associated with disease severity to a similar degree as C-reactive protein, the criterion-standard marker in AP. Further studies are warranted to define their clinical role.