bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunomodulatory drugs in the treatment of multiple myeloma
Authors: Abe Yu , Ishida Tadao
Published: June 2019

The prognosis of multiple myeloma was quite poor in the last century, but it has significantly improved with the incorporation of novel agents, immunomodulatory drugs (IMiDs) and proteasome inhibitors. Thalidomide was first developed as a sedative in 1950s, but it was withdrawn from the market because of teratogenicity. In 1990s, however, thalidomide received attention due to the discovery of its anticancer potential derived from antiangiogenic and immunomodulatory activities, and its therapeutic effect on myeloma. In 2006, the U.S. Food and Drug Administration approved the use of thalidomide under strict control for the treatment of multiple myeloma. After that, two new IMiDs, lenalidomide and pomalidomide, were developed for the sake of more antitumor activity and less adverse events than thalidomide. The molecular mechanism of action of IMiDs remained unclear for a long time until 2010 when the protein cereblon (CRBN) was identified as a primary direct target. IMiDs binds to CRBN and alters the substrate specificity of the CRBN E3 ubiquitin ligase complex, resulting in breakdown of intrinsic downstream proteins such as IKZF1 (Ikaros) and IKZF3 (Aiolos). There are many clinical trials of multiple myeloma using IMiDs under various conditions, and most of them show the efficacy of IMiDs. Nowadays lenalidomide plays a central role in both newly diagnosed and relapsed/refractory settings, mainly in combination with other novel agents such as proteasome inhibitors and monoclonal antibodies. This review presents an overview of recent advances in immunomodulatory drugs in the treatment of multiple myeloma.
DNA Methylation Changes in the Sperm of Captive-Reared Fish: A Route to Epigenetic Introgression in Wild Populations
Authors: Rodriguez Barreto Deiene , Garcia de Leaniz Carlos , Verspoor Eric , Sobolewska Halina , Coulson Mark , Consuegra Sofia
Published: June 2019

Interbreeding between hatchery-reared and wild fish, through deliberate stocking or escapes from fish farms, can result in rapid phenotypic and gene expression changes in hybrids, but the underlying mechanisms are unknown. We assessed if one generation of captive breeding was sufficient to generate inter- and/or transgenerational epigenetic modifications in Atlantic salmon. We found that the sperm of wild and captive-reared males differed in methylated regions consistent with early epigenetic signatures of domestication. Some of the epigenetic marks that differed between hatchery and wild males affected genes related to transcription, neural development, olfaction, and aggression, and were maintained in the offspring beyond developmental reprogramming. Our findings suggest that rearing in captivity may trigger epigenetic modifications in the sperm of hatchery fish that could explain the rapid phenotypic and genetic changes observed among hybrid fish. Epigenetic introgression via fish sperm represents a previously unappreciated mechanism that could compromise locally adapted fish populations.
DNA-segment-capture model for loop extrusion by structural maintenance of chromosome (SMC) protein complexes
Authors: Marko John F , De Los Rios Paolo , Barducci Alessandro , Gruber Stephan
Published: June 2019

Cells possess remarkable control of the folding and entanglement topology of long and flexible chromosomal DNA molecules. It is thought that structural maintenance of chromosome (SMC) protein complexes play a crucial role in this, by organizing long DNAs into series of loops. Experimental data suggest that SMC complexes are able to translocate on DNA, as well as pull out lengths of DNA via a ‘loop extrusion’ process. We describe a Brownian loop-capture-ratchet model for translocation and loop extrusion based on known structural, catalytic, and DNA-binding properties of the Bacillus subtilis SMC complex. Our model provides an example of a new class of molecular motor where large conformational fluctuations of the motor ‘track’—in this case DNA—are involved in the basic translocation process. Quantitative analysis of our model leads to a series of predictions for the motor properties of SMC complexes, most strikingly a strong dependence of SMC translocation velocity and step size on tension in the DNA track that it is moving along, with ‘stalling’ occuring at subpiconewton tensions. We discuss how the same mechanism might be used by structurally related SMC complexes (Escherichia coli MukBEF and eukaryote condensin, cohesin and SMC5/6) to organize genomic DNA.
Structure and ligand binding of the glutamine-II riboswitch
Authors: Huang Lin , Wang Jia , Watkins Andrew M , Das Rhiju , Lilley David M J
Published: June 2019

We have determined the structure of the glutamine-II riboswitch ligand binding domain using X-ray crystallography. The structure was solved using a novel combination of homology modeling and molecular replacement. The structure comprises three coaxial helical domains, the central one of which is a pseudoknot with partial triplex character. The major groove of this helix provides the binding site for L-glutamine, which is extensively hydrogen bonded to the RNA. Atomic mutation of the RNA at the ligand binding site leads to loss of binding shown by isothermal titration calorimetry, explaining the specificity of the riboswitch. A metal ion also plays an important role in ligand binding. This is directly bonded to a glutamine carboxylate oxygen atom, and its remaining inner-sphere water molecules make hydrogen bonding interactions with the RNA.
Long-term Outcomes of Patients With Human Herpesvirus 6 Encephalitis
Authors: Fida Madiha , Hamdi Ahmed M , Bryson Alexandra , Razonable Raymund R , Abu Saleh Omar
Published: June 2019

Human herpesviruses 6 (HHV-6) A and B cause encephalitis in patients with hematologic malignancies, especially those undergoing allogeneic hematopoietic stem cell transplantation. In this cohort of 10 patients, persistent neurologic deficits associated with moderate to severe bilateral hippocampal atrophy were characteristic long-term findings, despite prolonged antiviral treatment.
Long-Acting Lipoglycopeptides: “Lineless Antibiotics” for Serious Infections in Persons Who Use Drugs
Authors: Morrisette Taylor , Miller Matthew A , Montague Brian T , Barber Gerard R , McQueen R Brett , Krsak Martin
Published: June 2019

Background

Injection drug use is associated with serious infections. Due to challenges with medical management of addiction, relapses and additional infections are common. Persons who use drugs (PWUD) are more likely to leave against medical advice before completing treatment, which could result in treatment failure. Prolonged intravenous (IV) antimicrobial therapy in PWUD may be complicated by concern for IV catheter misuse, sometimes requiring prolonged hospitalization. Ideal alternatives would provide the following: (1) high success rate; (2) reduced rate of medical complications; (3) improved safety profiles; and (4) improved cost-effectiveness. Long-acting lipoglycopeptides present such opportunity for treatment of serious Gram-positive infections.

Methods

We performed a system-wide, retrospective analysis of adults admitted to University of Colorado Health from September 2015 to June 2018 and treated with dalbavancin or oritavancin based on clinical judgment of their treating physicians.

Results

Fifty-six patients met inclusion criteria (17 PWUD vs 39 non-PWUD). The PWUD group were younger, healthier by Charlson comorbidity index, more likely insured by Medicaid, and admitted for conditions requiring longer treatment. Ten patients were lost to follow-up. Of the patients with follow-up, clinical failure was met in 1 PWUD patient (6%) and 6 non-PWUD patients (15%) (P = .413). The median hospital length-of-stay reduction was 20 days (interquartile range [IQR], 10–30 days) in PWUD vs 11 days (IQR, 9–14 days) in non-PWUD; P = .133. Estimated median savings were $40 455.08 (IQR, $20 900.00–$62 700.00) in PWUD vs $19 555.08 (IQR, $15 375.08–$23 735.08) in non-PWUD; P = .065.

Conclusions

Long-acting lipoglycopeptides may be equally effective as standard-of-care, present a safety advantage, and secure earlier discharge and significant cost-savings.
Partially Dissecting Electron Fluxes in Both Photosystems in Spinach Leaf Disks during Photosynthetic Induction
Authors: Zhang Meng-Meng , Fan Da-Yong , Murakami Keach , Badger Murray R , Sun Guang-Yu , Chow Wah Soon
Published: June 2019

Photosynthetic induction, a gradual increase in photosynthetic rate on a transition from darkness or low light to high light, has ecological significance, impact on biomass accumulation in fluctuating light and relevance to photoprotection in strong light. However, the experimental quantification of the component electron fluxes in and around both photosystems during induction has been rare. Combining optimized chlorophyll fluorescence, the redox kinetics of P700 [primary electron donor in Photosystem I (PSI)] and membrane inlet mass spectrometry in the absence/presence of inhibitors/mediator, we partially estimated the components of electron fluxes in spinach leaf disks on transition from darkness to 1,000 ï¿½mol photonsï¿½m−2ï¿½s−1 for up to 10 min, obtaining the following findings: (i) the partitioning of energy between both photosystems did not change noticeably; (ii) in Photosystem II (PSII), the combined cyclic electron flow (CEF2) and charge recombination (CR2) to the ground state decreased gradually toward 0 in steady state; (iii) oxygen reduction by electrons from PSII, partly bypassing PSI, was small but measurable; (iv) cyclic electron flow around PSI (CEF1) peaked before becoming somewhat steady; (v) peak magnitudes of some of the electron fluxes, all probably photoprotective, were in the descending order: CEF1 > CEF2 + CR2 > chloroplast O2 uptake; and (vi) the chloroplast NADH dehydrogenase-like complex appeared to aid the antimycin A-sensitive CEF1. The results are important for fine-tuning in silico simulation of in vivo photosynthetic electron transport processes; such simulation is, in turn, necessary to probe partial processes in a complex network of interactions in response to environmental changes.
IgM anti-phosphorylcholine antibodies associate with senescent and IL-17+ T cells in SLE patients with a pro-inflammatory lipid profile
Authors: López Patricia , Rodríguez-Carrio Javier , Martínez-Zapico Aleida , Pérez-Álvarez Ángel I , Benavente Lorena , Caminal-Montero Luis , Suárez Ana
Published: June 2019

Objective

The aim was to evaluate whether T cell subsets and the lipid profile could be linked to the cardioprotective effect of IgM anti-phosphorylcholine (PC) antibodies in SLE.

Methods

Anti-PC antibodies were quantified by ELISA in 197 patients and 99 controls and analysed in relationship to clinical features, treatments and serum lipids. Carotid atheromatosis was evaluated by ultrasonography; Th1, Th17, Treg and CD4+CD28null cells by flow cytometry; and cytokine serum levels by immunoassays, in a subgroup of 120 SLE patients and 33 controls.

Results

IgM anti-PC serum levels were reduced in SLE patients compared with controls (P < 0.001) and were associated with age (β= −0.252; P = 0.002), high-density lipoprotein (HDL; β = 0.271; P = 0.001), low-density lipoprotein (LDL; β= −0.192; P = 0.017) and glucocorticoid treatment (β= −0.201; P = 0.012), whereas the IgG-to-IgM anti-PC ratio was increased (P = 0.007) and associated with age (β = 0.194; P = 0.028) and SLEDAI (β = 0.250; P = 0.005). Also, patients with clinical or subclinical cardiovascular disease exhibited reduced IgM anti-PC levels compared with their cardiovascular disease-free counterparts, regardless of glucocorticoid usage (P = 0.001). CD4+CD28null and Th17 cells were increased in SLE patients compared with controls (P < 0.01) and correlated inversely with IgM anti-PC levels. These associations were observed in patients displaying high triglyceride or low HDL levels, even after adjusting for clinical parameters and treatments (CD4+CD28null: β = −0.455, P = 0.001; Th17: β= −0.280, P = 0.035), but not in those with a normal lipid profile. High triglyceride and low HDL profiles were related to low IgM anti-PC and Treg levels, respectively, whereas both lipid profiles were associated with inflammatory markers and cytokines.

Conclusion

The present study provides evidence for an association of IgM anti-PC antibodies with pro-atherogenic T cell subsets in SLE, with a high triglyceride/low HDL lipid profile playing a facilitating major role.
MONITORING AND CHARACTERISATION OF NEW EVIDENCE OF NATURAL RADIONUCLIDES IN ROCK OUTCROPS IN PARAÍBA—BRAZIL
Authors: do Nascimento Santos Josineide Marques , dos Santos Júnior José Araújo , dos Santos Amaral Romilton , Fernández Zahily Herrero , Bezerra Jairo Dias , Cavalcanti Freire Bezerra Mariana Brayner , da Silva Arykerne Nascimento Casado , de Araújo Eduardo Eudes Nóbrega , Rojas Lino Angel Valcárcel , Milan Marvic Ortueta , de Barros Correia Filipe Lopes
Published: June 2019

The radiometric monitoring carried out in the present study allowed the discovery of anomalous granite outcrops in natural radionuclides in the rural area of São Mamede in the state of Paraíba, Brazil. The characterisation study made it possible to determine maximum specific concentrations of approximately 199 kBq kg−1 of 238U, 85 kBq kg−1 of 226Ra, 26 kBq kg−1 of 232Th and 24 kBq kg−1 of 40K. Models for environmental dosimetry were applied, which resulted in obtaining the following quantities: radium equivalent (Raeq), indices of external (Hex), internal (Hin) and representative (Iyr) damage, and the effective outdoor dose (HE). The maximum results presented were approximately 123 kBq kg−1, 332, 562, 832, and 68 mSv y−1, respectively. Consequently, it was possible to define the region as of high radioactive background due to isolated rocky outcrops located in the rural area of the mentioned municipality.
‘No Man’s Land’: Disability, Rehabilitation, Welfare Policy and the British Ex-Service Migrant in Australia, 1918–39
Authors: Robinson Michael
Published: June 2019

An inter-war analysis of the British and Australian departments charged with compensating disabled First World War veterans and the British ex-service migrant in inter-war Australia illustrates how nation-states have failed to unify welfare and disability rehabilitation. Contemporary welfare states continue to codify and establish categories of prioritisation regarding communities with disabilities for public finance administered by national government departments. This binational case study identifies reoccurring type one and type two error problems: policy can deny legitimate claims for state assistance while also validating and financing potentially illegitimate claims. This underlines the factors that dictate which error type is ruled to be the least significant and the impact the resulting model has on individual claimants. This study reinforces the thesis of David Gerber who stresses the ahistorical centrality of ‘biopolitics’ or the relationship between societal and political perceptions of a conflict on state policy, in the treatment of veteran communities.
XI The Eighteenth Century
Authors: Dye Jill , Glover Danni , Scott Robert , Harriman-Smith James
Published: June 2019

This chapter has four sections: 1. General and Prose; 2. The Novel; 3. Poetry; 4. Drama. Section 1 is by Jill Dye; section 2 is by Danni Glover; section 3 is by Robert Scott; section 4 is by James Harriman-Smith.
Extended Hopanoid Loss Reduces Bacterial Motility and Surface Attachment and Leads to Heterogeneity in Root Nodule Growth Kinetics in a Bradyrhizobium-Aeschynomene Symbiosis
Authors: Belin Brittany J. , Tookmanian Elise M. , de Anda Jaime , Wong Gerard C. L. , Newman Dianne K.
Published: June 2019

Hopanoids are steroid-like bacterial lipids that enhance membrane rigidity and promote bacterial growth under diverse stresses. Hopanoid biosynthesis genes are conserved in nitrogen-fixing plant symbionts, and we previously found that the extended (C35) class of hopanoids in Bradyrhizobium diazoefficiens are required for efficient symbiotic nitrogen fixation in the tropical legume host Aeschynomene afraspera. Here, we demonstrate that the nitrogen-fixation defect conferred by extended hopanoid loss can be fully explained by a reduction in root nodule sizes rather than per-bacteroid nitrogen-fixation levels. Using a single-nodule tracking approach to quantify A. afraspera nodule development, we provide a quantitative model of root nodule development in this host, uncovering both the baseline growth parameters for wild-type nodules and a surprising heterogeneity of extended hopanoid mutant developmental phenotypes. These phenotypes include a delay in root nodule initiation and the presence of a subpopulation of nodules with slow growth rates and low final volumes, which are correlated with reduced motility and surface attachment in vitro and lower bacteroid densities in planta, respectively. This work provides a quantitative reference point for understanding the phenotypic diversity of ineffective symbionts in A. afraspera and identifies specific developmental stages affected by extended hopanoid loss for future mechanistic work.
An overview of reactive arthritis
Authors: Pennisi Megan , Perdue Jacqueline , Roulston Tessa , Nicholas Joyce , Schmidt Eric , Rolfs Jenna
Published: June 2019

Reactive arthritis, also known as Reiter syndrome, is a spondyloarthropathy that typically follows a urogenital or gastrointestinal infection, and is characterized by conjunctivitis, urethritis, and arthritis. The frequency of reactive arthritis in the United States is estimated at 3.5 to 5 patients per 100,000. Physician assistants (PAs) can manage the condition; therefore, they should be familiar with the disease's signs and symptoms, diagnostic criteria, and treatment regimens. Without proper management, reactive arthritis can progress to a chronic destructive arthritis. Prompt recognition of the condition is key to early intervention and a better patient outcome with fewer complications.
The Impact of Positive Space Training on Students’ Communication With LGBTTQ+ Communities
Authors: Haghiri-Vijeh Roya , McCulloch Tara , Atack Lynda , Bedard Gabriel
Published: June 2019

The lesbian, gay, bisexual, transgender, two-spirit, and queer (LGBTTQ+) communities have experienced discrimination from nurses and other health care professionals, resulting in health inequity. The purpose of this study was to examine the impact of positive space training on students’ knowledge and comfort level with LGBTTQ+ communities. A quasi-experimental study with surveys and focus groups was conducted with 160 students. All participants perceived an increase in knowledge and comfort in communicating with LGBTTQ+ people after training. Positive space training can be part of the bank of learning strategies we offer students to increase their knowledge and comfort when interacting with LGBTTQ+ communities.
Biological treatments for severe asthma
Authors: Assaf Sara M. , Hanania Nicola A.
Published: June 2019

Purpose of review

Asthma is a heterogenous disease associated with different phenotypes and endotypes. The unmet needs with severe asthma have led to the emergence of potential therapeutic targets beyond the existing therapies. Recently, several biologics were examined and some have now been approved to target T2 airway inflammation in patients with severe disease. We provide an overview of recently approved biologic, those which are emerging and highlight unmet needs in this area.

Recent findings

Multiple biologics targeting T2 high asthma are now available for clinical use in the appropriate groups of severe asthma. These target overlapping phenotypes, which include allergic and eosinophilic asthma. Available biologics were shown to improve outcomes that include the reduction of exacerbations and improvement of lung function. Some have also demonstrated improvement in patient-reported outcomes. Some of these biologics have also demonstrated beneficial effects on associated asthma comorbidities. Biomarkers help predict response to certain biologics, although only few currently exist. Emerging biologics blocking other pathways of airway inflammation are under development. Several small molecule antagonists and inhibitors are also in development. Biologics and therapies targeting T2 low or non-T2 asthma are needed.

Recently approved biologic therapies improve asthma outcomes in subset of patients. Future research to uncover better predictors of response can improve the precise approach to therapy of patients with severe disease.
Common and different roles of IL-4 and IL-13 in skin allergy and clinical implications
Authors: Roesner Lennart M. , Zeitvogel Jana , Heratizadeh Annice
Published: June 2019

Purpose of review

This review summarizes the mode of action of IL-4 and IL-13 in skin allergy, upcoming therapeutics and depicts key outcomes of the latest clinical trials.

Recent findings

Atopic dermatitis is considered to be one of the most common inflammatory skin disease in industrialized countries. Accompanied by strong pruritus, atopic dermatitis has a significant impact on quality of life in severely affected individuals. Aside from unspecific immunosuppressant medications, therapeutics targeting the key cytokines IL-4 and IL-13 and their downstream mediators are under development or have been approved just recently with outstanding potential.

The recent development of several biologics and small compounds has the potential to revolutionize the treatment of atopic dermatitis, and applying this set of state-of-the-art drugs will provide a unique chance to gain insights into this skin disorder, patient subgroups, and key inflammatory mediators.
Impact of infections in autoimmune rheumatic diseases and pregnancy
Authors: Jara Luis J. , Cruz-Dominguez Maria del Pilar , Saavedra Miguel A.
Published: June 2019

Purpose of review

To provide an update about the impact of infections in autoimmune rheumatic diseases (ARDs), from the analysis of the role of infections in pregnant women without ARDs, to the identification of maternal–fetal infections and their role in the maternal–fetal outcome of women with ARDs.

Recent findings

Recent studies indicate that patients with ARDs and pregnancy are also susceptible to presenting infections of varying degrees, including serious infections, which contribute to the morbidity and mortality observed in pregnancy and postpartum of these patients.

Any type of infectious agent will interact with a hormonal, immunological and metabolic environments modified by ARD, treatments, and by the changes inherent in pregnancy. Therefore, infections in the pregnancy of patients with ARDs should be considered as a risk factor for an unfavorable maternal–fetal outcome.

The recognition of infections in the pregnancy of ARDs as a risk factor is the first step to prevent, identify, and treat them in a timely manner, and thus contribute to the favorable course of pregnancy in these patients. Patients with ARDs and major organ involvement, use of high doses of steroids, immunosuppressant and biological therapies, adolescence, and obesity are populations susceptible to developing infections.
Are Routine Postoperative Computer Tomography Scans Warranted for All Patients After Operative Fixation of Pelvic Ring Injuries?
Authors: Cronin Kevin J. , Hockensmith Lindsay , Hayes Christopher B. , Zuelzer David , Jacobs Cale A. , Moghadamian Eric S.
Published: June 2019

Objective:

To evaluate the efficacy of routine postoperative computed topography (CT) scan after percutaneous fixation of unstable pelvic ring injuries.

Design:

Retrospective chart review.

Setting:

Level I Trauma Center.

Patients/Participants:

A total of 362 consecutive patients underwent operative fixation of unstable pelvic ring injuries during the study period.

Intervention:

Postoperative CT scan of the pelvis was obtained in 331 (91%) of the 362 patients treated operatively for unstable pelvic ring injuries.

Main Outcome Measurements:

Revision surgery based on routine postoperative CT scan.

Results:

Two patients (0.55%) returned to the operating room on the basis of postoperative CT scans due to malpositioned implants. There were no significant differences of age, sex, body mass index, Injury Severity Score, mechanism of injury, smoking status, or diabetes status between those who did and did not undergo revision surgery. A dysmorphic pelvis was identified in 154 (47%) patients. Both patients undergoing revision surgery were determined to have a dysmorphic pelvis while no patients with normal pelvic anatomy returned to the operating room based on postoperative CT (2/154, 1.3% vs. 0/177, 0%, P = 0.22).

Conclusions:

Although there remains a role for postoperative CT scans in the appropriately selected patient, in the hands of experienced orthopaedic traumatologists, patients with adequate intraoperative fluoroscopy and a nondysmorphic pelvis may not require routine postoperative three-dimensional imaging.

Level of Evidence:

Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
The Importance of Natural History
Authors: Weinstein Stuart L.
Published: June 2019

In a traditional view, the natural history of a condition or a disease tells us of the adult consequences of that entity, be it benign or otherwise. This knowledge then provides guidance as to who needs treatment, and allows us to assess whether our treatments alter an otherwise adverse natural history in a positive way without introducing iatrogenic complications. However, in the new paradigm for health care delivery of value-based care, we need to be able to express natural history in additional terms of burden of disease. This is something that lawmakers and people who pay for health care can understand and has a comparative value. It also serves as a benchmark to show the effectiveness of interventions aimed at reducing disease burden. In this paper, I will discuss why this POSNA symposium is important and make some recommendations on directions where we as individuals and as a professional society should be putting in our efforts and resources.
The Natural History of Early-onset Scoliosis
Authors: Karol Lori A.
Published: June 2019

Background:

Early-onset scoliosis (EOS) is defined as the diagnosis of a spinal deformity before the age of 5 years. It can be divided into idiopathic, neuromuscular/syndromic, and congenital etiologies.

Methods:

The literature on the natural history of EOS was summarized.

Results:

The natural history varies with the etiology of EOS. Idiopathic curves may benefit from early serial casting. The natural history of neuromuscular and syndromic scoliosis is highly dependent on the natural history of the underlying disorder. Congenital scoliosis has a variable prognosis depending on the location and extent of the congenital malformations.

Conclusions:

Treatment of children with EOS is customized to the particular disorder. While lack of treatment has been shown to lead to increased mortality, extensive early definitive fusion may lead to thoracic insufficiency. Delaying definitive surgery and the use of growing instrumentation may provide benefit in maintaining pulmonary health.

Clinical Relevance:

Potential disturbance of growth must be considered in the treatment of young children with scoliosis.
How Good is the Evidence Linking Acetabular Dysplasia to Osteoarthritis?
Authors: Cooperman Daniel R.
Published: June 2019

Background:

A common claim in the orthopaedic literature is that acetabular dysplasia (AD) exists when the center-edge angle of Wiberg (CE angle) is <20 degrees and that AD leads to osteoarthritis (OA). Our purpose is to evaluate the validity of the linkage between AD and OA.

Methods:

We assess and discuss the theories and the empirical evidence relating AD to OA. Moreover, we test the rule that hips with a CE angle <20 degrees will develop OA by 65 years of age, by looking for exceptions to this rule.

Results:

Wiberg and Cooperman and colleagues present 30 ideal patients for assessing the relationship between AD and OA. Each was arthritis free, with stable AD, CE angle <20 degrees, without signs of subluxation. They were all followed and all developed OA. In the studies by Stulberg and colleagues, and Jacobsen and colleagues, every patient presented with OA, making it difficult to be certain about the appearance of the hip before the onset of OA. In the study by Murphy and colleagues, we have the same problem, as an unknown number of patients already had OA at first assessment. All of these studies used different schemes for diagnosing OA, making the studies difficult to compare. Most of the patients in the studies were of Northern European ancestry, making the results difficult to generalize to other populations. Four patients had CE angles <20 degrees and did not develop severe arthritis by 65 years of age.

Conclusions:

Our conclusions apply directly to patients of Northern European ancestry. A few patients with stable, mild AD (CE angle 15 to 19 degrees) will be arthritis free at 65 years of age. Almost all patients with stable AD develop OA by 65 years of age. Unstable AD (CE angle <20 degrees, with subluxation) always leads to OA by 65 years of age. It is probably reasonable to extend these conclusions to other populations, but the reader must be prepared to re-evaluate them, as more data accumulates.
Utility of Patient-reported Symptoms and Health Conditions for Predicting Surgical Candidacy and Utilization of Surgery via an Outpatient Spine Clinic Nomogram
Authors: Pennington Zach , Lubelski Daniel , Tanenbaum Joseph , Ahmed A. Karim , Rosato Marissa , Passias Peter , Sciubba Daniel M.
Published: June 2019

Study Design:

Retrospective cohort.

Objective:

Identify the nonradiographic predictors of a patient’s decision to undergo elective spine surgery.

Summary of Background Data:

Up to 132 million people seek elective evaluation by spine surgeons annually, though 55%–82% of specialty referrals may be inappropriate. We sought to determine which clinical and psychosocial factors are associated with surgical utilization by patients seeking surgical evaluation for degenerative spine pathologies.

Materials and Methods:

Consecutive elective outpatient visits seen in a single clinic between May 2016 and April 2017 for degenerative spine pathologies were reviewed. Data were collected on presenting symptoms, baseline medical illness, demographics, and previous spine care. Multivariable logistic regressions were performed to determine which factors were associated with surgical candidacy and surgical utilization.

Results:

A total of 353 patients were seen during the period reviewed, of which 144 had complete medical records. Our cohort included 90 nonsurgical candidates, 25 surgical candidates who declined surgery, and 29 patients who underwent surgery. In multivariable analysis, factors negatively associated with surgical candidacy were age, a history of smoking, and osteoporosis, where those positively associated with surgical candidacy were reports of spine-specific pain, higher Charlson Comorbidity Index, pain medication use, number of neurological symptoms, and being myelopathic. Factors positively associated with surgical utilization included proportion of all complaints that were neurological in nature, being myelopathic, higher Charlson Comorbidity Index, and report of pain as chronic, whereas being osteoporotic was negatively associated with surgical use. A receiver operating curve constructed for these models produced c-statistics of 0.75 and 0.80, respectively.

Conclusions:

Our results suggest that the results of standard clinic intake questions, such as review of systems, medical history, and chief complaints, may be predictive of surgical candidacy before evaluation by a surgeon. The present pilot study suggests a preliminary algorithm that can be further validated and expanded upon to help decide on optimal patient referrals to spine surgery specialists.
Interprofessional Shared Decision-Making in the ICU: A Systematic Review and Recommendations From an Expert Panel*
Authors: Michalsen Andrej , Long Ann C. , DeKeyser Ganz Freda , White Douglas B. , Jensen Hanne I. , Metaxa Victoria , Hartog Christiane S. , Latour Jos M. , Truog Robert D. , Kesecioglu Jozef , Mahn Anna R. , Curtis J. Randall
Published: June 2019

Objectives:

There is growing recognition that high-quality care for patients and families in the ICU requires exemplary interprofessional collaboration and communication. One important aspect is how the ICU team makes complex decisions. However, no recommendations have been published on interprofessional shared decision-making. The aim of this project is to use systematic review and normative analysis by experts to examine existing evidence regarding interprofessional shared decision-making, describe its principles and provide ICU clinicians with recommendations regarding its implementation.

Data Sources:

We conducted a systematic review using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases and used normative analyses to formulate recommendations regarding interprofessional shared decision-making.

Study Selection:

Three authors screened titles and abstracts in duplicate.

Data Synthesis:

Four papers assessing the effect of interprofessional shared decision-making on quality of care were identified, suggesting that interprofessional shared decision-making is associated with improved processes and outcomes. Five recommendations, largely based on expert opinion, were developed: 1) interprofessional shared decision-making is a collaborative process among clinicians that allows for shared decisions regarding important treatment questions; 2) clinicians should consider engaging in interprofessional shared decision-making to promote the most appropriate and balanced decisions; 3) clinicians and hospitals should implement strategies to foster an ICU climate oriented toward interprofessional shared decision-making; 4) clinicians implementing interprofessional shared decision-making should consider incorporating a structured approach; and 5) further studies are needed to evaluate and improve the quality of interprofessional shared decision-making in ICUs.

Conclusions:

Clinicians should consider an interprofessional shared decision-making model that allows for the exchange of information, deliberation, and joint attainment of important treatment decisions.
Complex Reconstruction of a Pelvic Marjolin’s Ulcer Arising from Hidradenitis Suppurativa
Authors: Buchanan Lauren E. , Campbell Chris A.
Published: June 2019

The chronic inflammation of hidradenitis suppurativa can cause painful nodules, draining abscesses, sinus tracts, and fibrous scars. This long-term cutaneous inflammation in rare circumstances can lead to malignant transformation producing an aggressive cutaneous malignancy referred to as a Marjolin’s ulcer. Particularly when a Marjolin’s ulcer involves the sacral region, resection and reconstruction can be challenging. We present the case of a patient with a recurrent Marjolin’s ulcer originating from a hidradenitis wound bed overlying and involving the sacrum. Previous radiation, large defect size, and sacral and perianal involvement necessitated the use of a multiflap approach. An extended transpelvic vertical rectus abdominis myocutaneous flap, bilateral gluteal advancement flaps, and a delayed transverse back flap were used to reconstruct the defect after abdominoperineal resection and nerve-sparing partial sacrectomy. Flap choice was derived by dividing the defect into anatomic subunits and considering intrapelvic defect volume, creating a systematic approach that led to successful reconstruction and functional restoration.
Establishing and Maintaining a Quality and Safety Program on Labor and Delivery
Authors: MEHLHAFF KRISTA M. , PETTKER CHRISTIAN M.
Published: June 2019

There is no single framework for a successful obstetric patient safety program. However, there are ample resources for the important components needed to create a patient safety program. All labor and delivery units should formulate their own quality and safety program that is individualized to the patients and staff that they serve. Here we will lay out the infrastructure as has been supported by the literature and reinforced in our experience.
Culturing Discarded Peripheral Human Corneal Endothelial Cells From the Tissues Deemed for Preloaded DMEK Transplants
Authors: Parekh Mohit , Romano Vito , Ruzza Alessandro , Kaye Stephen B. , Ponzin Diego , Ahmad Sajjad , Ferrari Stefano
Published: June 2019

Purpose:

To investigate if the peripheral corneal endothelium that is discarded after the preparation of preloaded Descemet membrane endothelial keratoplasty (DMEK) grafts for transplantation could be successfully used for corneal endothelial cell culture.

Methods:

Complete Descemet membrane–endothelial complex (11.00 mm) was peeled from research-grade tissues (n = 15). The periphery (2.75 mm) of clinical-grade tissues (n = 15) deemed for preloaded DMEK transplants was gently peeled and preserved for 48 hours in tissue culture media, followed by centrifugation at 1000 rpm for 5 minutes. After enzymatic digestion, the cells from each group were plated in 2 different wells of an 8-well chamber slide. Media were refreshed and the confluence rate was monitored every alternate day. Live/dead staining and the expression of ZO-1, Tag1A3, Tag2A12, and Ki-67 markers were used to assess the viability, morphology, tight-junctions, cell area, and number of proliferative cells. The Wilcoxon and Student's t test were applied, where P < 0.05 was deemed statistically significant.

Results:

Average endothelial cell density at confluence was 2,352 cells/mm2 from complete endothelium and 2,510 cells/mm2 from peripheral endothelium (P = 0.0351). The confluence rate (%), hexagonality (%), polymorphism (%), cell area (μm2), and Ki-67 positivity (%) did not differ between both groups (P > 0.05). All the antibodies were expressed in both groups at confluence.

Conclusions:

The discarded peripheral endothelial cells obtained after preparing a preloaded DMEK graft for clinical application has a huge reservoir of healthy endothelial cells having proliferative potential. Using these discarded tissue pieces from donor tissues will significantly increase the primary source of healthy donor endothelial cells for regenerative treatments, which are otherwise difficult to obtain.
Six-Month Outcomes After High Hyperopia Correction Using Laser-Assisted In Situ Keratomileusis With a Large Ablation Zone
Authors: Gauthier-Fournet Laurent , Penin Franck , Arba Mosquera Samuel
Published: June 2019

Purpose:

To evaluate refractive and visual outcomes of laser-assisted in situ keratomileusis (LASIK) to treat high hyperopia using an aberration-neutral profile and large ablation zone.

Methods:

This was a retrospective, consecutive observational case series at Helios Ophtalmologie, St. Jean-de-Luz, France. One hundred forty-six consecutive eyes of 77 patients who underwent LASIK with mechanical microkeratome to correct hyperopia with correction in the maximum hyperopic meridian strictly higher than +5 D (mean + 6.6 ± 1.0 D) were included. Procedures were performed with an Amaris 750S excimer laser (Schwind eye-tech-solutions GmbH, Kleinostheim, Germany) using an aberration-neutral profile, a 6.7 ± 0.1 mm optical zone, and a 9.2 ± 0.1 mm total ablation zone. Refractive results, predictability, safety, and efficacy were evaluated at 6 months postoperatively.

Results:

At 6 months postsurgery, the mean manifest refraction spherical equivalent was −0.06 ± 0.83 D and the mean cylinder was 0.42 ± 0.35 D. Sixty-six percent of eyes were within ±0.50 D of the attempted spherical equivalent correction. Six months postoperatively, 60% of eyes achieved an uncorrected distance visual acuity of 20/20 or better. Ten percent of eyes lost 1 line of corrected distance visual acuity and 4% gained a line. No eyes lost more than 2 Snellen lines of corrected distance visual acuity at any follow-up.

Conclusions:

High hyperopia correction with LASIK using an aberration-neutral profile and large ablation zone provides good efficacy, safety, predictability, and visual outcomes.
Community Health Workers as Organizational Actors in Community Health Centers in 4 Gulf Coast States
Authors: Sherman Mya , Covert Hannah , Lichtveld Maureen
Published: June 2019

Community health workers (CHWs) are recognized for bridging communities and health care systems; yet, there is limited discussion of CHWs' roles as organizational actors within and outside clinics. Individual semistructured interviews (n = 21) were conducted in 4 Gulf Coast states with CHWs and supervisors to examine the bridging function of CHWs from a community health center's perspective. Results highlight that CHWs can function as gatekeepers and ambassadors who extend the clinics' reach in the community, enhance patient access to resources, and improve organizational efficiency. This study demonstrates the value that CHWs can bring for clients and clinics as organizational actors.
Developing Emerging Leaders to Support Team-Based Primary Care
Authors: Coleman Katie , Wagner Edward H. , Ladden Maryjoan D. , Flinter Margaret , Cromp DeAnn , Hsu Clarissa , Crabtree Benjamin F. , McDonald Sarah
Published: June 2019

Teams are increasingly used to deliver high-quality, accessible primary care, yet few leadership programs support the development of team-based care leadership capabilities. The 12-month Emerging Leaders program presents a prototype for how interdisciplinary training targeting frontline staff might be implemented. Emerging Leaders training included didactic content, mentorship, applied peer-to-peer learning, and personal leadership development components delivered in person and virtually. Attendance at training events was high. Nominators and Emerging Leaders noted improvements in knowledge, skills, and attitudes of program participants. Forty percent of participants went on to promotions or new jobs.
Five-Year Trends in Reported National Football League Injuries
Authors: Bedard Gillian , Wyndham Lawrence David
Published: June 2019

Objective:

To determine the incidence of all-cause injury and concussion in the National Football League (NFL) over a 5-season time span (2012-2016).

Design:

Prospective descriptive epidemiological study.

Setting:

National Football League Injury Report data from 2012 to 2016.

Participants:

National Football League players.

Interventions:

None (descriptive study).

Main Outcome Measures:

Injury report data were collected prospectively for all NFL injuries from 5 seasons (2012-2016). The incidences of reported concussions, knee injuries, and all-cause injury were compared across the 5 seasons using the Kruskal–Wallis rank-sum test.

Results:

A total of 10 927 injuries were identified across the 5 seasons, including 752 (6.9%) concussions. The top 3 most injured areas included the knee (17.2%), ankle (13.6%), and shoulder (8.8%). Defensive backs consistently had the highest number of all-cause injuries per season. When comparing across years, there was a significant decrease in all-cause injury in 2016 compared with 2015, a significant decrease in knee injuries in 2016 compared with 2015, and a significant increase in concussion in 2015 compared with 2014 (P < 0.05).

Conclusions:

Reported all-cause injury incidence and knee injury incidence is currently on the decline. However, reported concussion incidence has recently increased, perhaps due to increased awareness and rule changes implemented to aid in the detection and treatment of concussion. Strategies to reduce injury and improve injury awareness should continue to be explored.
Recent Advances in Cognitive Behavioral Therapy For Digestive Disorders and the Role of Applied Positive Psychology Across the Spectrum of GI Care
Authors: Feingold Jordyn , Murray Helen B. , Keefer Laurie
Published: June 2019

Background:

Although cognitive behavior therapies (CBTs) have shown great promise in the reduction of symptom burden from as well as anxiety around various gastrointestinal (GI) disorders, there are substantial issues involving the scalable delivery of such interventions within the clinical setting of a gastroenterology practice, leaving most patients without access to psychological care.

Goals:

This paper discusses the application of positive psychology principles and techniques for adoption by various GI providers to initiate early, effective psychological care for patients with GI disorders, saving CBTs for more complex cases.

Study/Results:

Authors provide a comprehensive framework of patient well-being known as REVAMP, which is consistent with CBT principles, and elaborate on research and interventions that can be adopted within the gastroenterology practice setting. Building positive resources can bolster patients with GI disorders against comorbid psychological and psychiatric distress.

Conclusions:

Positive psychology interventions can be implemented within gastroenterology practice. Research is necessary to evaluate the efficacy and acceptability of positive psychology interventions among patients with different digestive disorders and baseline psychological characteristics, as well as the feasibility of administration by different clinicians in the gastroenterology practice setting.
A Comprehensive Analysis of Liver Transplantation Outcomes Among Ethnic Minorities in the United States
Authors: Kaswala Dharmesh H. , Zhang Julia , Liu Andy , Sundaram Vinay , Liu Benny , Bhuket Taft , Wong Robert J.
Published: June 2019

Goals:

The aim of this study was to perform a comprehensive assessment of liver transplant (LT) outcomes among US adults with a specific focus on understanding race/ethnicity-specific disparities.

Background:

Despite improvements in the liver allocation and LT-related care, disparities in LT outcomes persist.

Study:

Using data from the 2005 to 2016 United Networks for Organ Sharing LT registry, we evaluated waitlist survival, probability of receiving LT, and post-LT survival among US adults stratified by race/ethnicity and liver disease etiology. Kaplan-Meier methods evaluated unadjusted waitlist and post-LT outcomes, and multivariate regression models evaluated adjusted waitlist and post-LT outcomes.

Results:

Among 88,542 listed for LT patients (41.3% hepatitis C virus, 25.3% alcoholic liver disease, 22.3% nonalcoholic steatohepatitis, 11.1% hepatitis C virus/alcoholic liver disease), significant race/ethnicity-specific disparities were observed. Compared with non-Hispanic whites, Hispanics had a significantly lower risk of waitlist death [hazard ratio (HR)=0.84, 95% confidence interval (CI): 0.79-0.90, P<0.001]. Compared with non-Hispanic whites, significantly lower likelihood of receiving LT was observed in African Americans (HR=0.94, 95% CI: 0.91-0.98, P<0.001), Hispanics (HR=0.70, 95% CI: 0.68-0.73, P<0.001) and Asians (HR=0.74, 95% CI: 0.69-0.80, P<0.001). Compared with non-Hispanic whites, African Americans had a significantly higher risk of 5-year post-LT death (HR=1.31, 95% CI: 1.23-1.39, P<0.001).

Conclusion:

Among US adults awaiting LT, significant race/ethnicity-specific disparities in LT outcomes were observed. Despite evaluating an era after implementation of the Model for End-Stage Liver Disease, ethnic minorities continue to demonstrate a lower probability of receiving LT, and significantly higher risk of death post-LT in African Americans.