bluuebunny/crossref_metadata_2025 huggingface dataset:
Fiber cables in leaf blades of Typha domingensis and their absence in Typha elephantina: a diagnostic character for phylogenetic affinity
Authors: Witztum Allan , Wayne Randy
Published: January 2016

Vertical fiber cables anchored in horizontal diaphragms traverse the air-filled lacunae of the tall, upright, spiraling leaf blades of Typha domingensis, T. angustifolia, T. latifolia and T. × glauca. The fiber cables may make a mechanical contribution to leaf blade stiffness while allowing flexibility under windy conditions. We examined the very tall, upright, spiraling leaf blades of T. elephantina, which can be over 4 m long, for fiber cables. In the tall species of Typha, there are two alternative architectures for upright leaf blades. T. domingensis utilizes fiber cables to enhance stiffness in the tall, upright concavo-convex leaf blades, whereas T. elephantina may maintain their tall stature in the absence of fiber cables by having a different cross-sectional geometry. These alternative architectures can be used as a diagnostic character along with other morphological characters to assess phylogenetic affinity in Typha. The very tall T. elephantina which lacks fiber cables may be more closely related to the much shorter T. minima, which also has no cables, than to the tall T. domingensis and T. angustifolia, both of which have prominent fiber cables. T. elephantina and T. minima share other morphological characters as well.
My oh my(osin): Insights into how auditory hair cells count, measure, and shape
Authors: Pollock Lana M. , Chou Shih-Wei , McDermott Brian M.
Published: January 2016

The mechanisms underlying mechanosensory hair bundle formation in auditory sensory cells are largely mysterious. In this issue, Lelli et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201509017) reveal that a pair of molecular motors, myosin IIIa and myosin IIIb, is involved in the hair bundle’s morphology and hearing.
Muscle versus Snail: Muscle wins
Authors: Simoes Sergio , Tepass Ulrich
Published: January 2016

Epithelial–mesenchymal transitions (EMTs) are often governed by the transcription factor Snail and entail the loss of apical junctions from epithelial cells. In this issue, Weng and Wieschaus (2016. J Cell Biol. http://dx.doi.org/10.1083/jcb.201508056) report that actomyosin contractility can strengthen junctions to override Snail-dependent junctional disassembly and postpone EMT during Drosophila melanogaster gastrulation.
Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide
Authors: Madera Sharline , Rapp Moritz , Firth Matthew A. , Beilke Joshua N. , Lanier Lewis L. , Sun Joseph C.
Published: January 2016

Type I interferon (IFN) is crucial in host antiviral defense. Previous studies have described the pleiotropic role of type I IFNs on innate and adaptive immune cells during viral infection. Here, we demonstrate that natural killer (NK) cells from mice lacking the type I IFN-α receptor (Ifnar−/−) or STAT1 (which signals downstream of IFNAR) are defective in expansion and memory cell formation after mouse cytomegalovirus (MCMV) infection. Despite comparable proliferation, Ifnar−/− NK cells showed diminished protection against MCMV infection and exhibited more apoptosis compared with wild-type NK cells. Furthermore, we show that Ifnar−/− NK cells express increased levels of NK group 2 member D (NKG2D) ligands during viral infection and are susceptible to NK cell–mediated fratricide in a perforin- and NKG2D-dependent manner. Adoptive transfer of Ifnar−/− NK cells into NK cell–deficient mice reverses the defect in survival and expansion. Our study reveals a novel type I IFN–dependent mechanism by which NK cells evade mechanisms of cell death after viral infection.
Identification of CD112R as a novel checkpoint for human T cells
Authors: Zhu Yuwen , Paniccia Alessandro , Schulick Alexander C. , Chen Wei , Koenig Michelle R. , Byers Joshua T. , Yao Sheng , Bevers Shaun , Edil Barish H.
Published: January 2016

T cell immunoglobulin and ITIM domain (TIGIT) and CD226 emerge as a novel T cell cosignaling pathway in which CD226 and TIGIT serve as costimulatory and coinhibitory receptors, respectively, for the ligands CD155 and CD112. In this study, we describe CD112R, a member of poliovirus receptor–like proteins, as a new coinhibitory receptor for human T cells. CD112R is preferentially expressed on T cells and inhibits T cell receptor–mediated signals. We further identify that CD112, widely expressed on antigen-presenting cells and tumor cells, is the ligand for CD112R with high affinity. CD112R competes with CD226 to bind to CD112. Disrupting the CD112R–CD112 interaction enhances human T cell response. Our experiments identify CD112R as a novel checkpoint for human T cells via interaction with CD112.
IL-33 amplifies an innate immune response in the degenerating retina
Authors: Xi Hongkang , Katschke Kenneth J. , Li Yun , Truong Tom , Lee Wyne P. , Diehl Lauri , Rangell Linda , Tao Jianhua , Arceo Rommel , Eastham-Anderson Jeffrey , Hackney Jason A. , Iglesias Antonio , Cote-Sierra Javier , Elstrott Justin , Weimer Robby M. , van Lookeren Campagne Menno
Published: January 2016

Age-related macular degeneration (AMD), a leading cause of vision impairment in the ageing population, is characterized by irreversible loss of retinal pigment epithelial (RPE) cells and photoreceptors and can be associated with choroidal neovascularization. Mononuclear phagocytes are often present in AMD lesions, but the processes that direct myeloid cell recruitment remain unclear. Here, we identify IL-33 as a key regulator of inflammation and photoreceptor degeneration after retina stress or injury. IL-33+ Müller cells were more abundant and IL-33 cytokine was elevated in advanced AMD cases compared with age-matched controls with no AMD. In rodents, retina stress resulted in release of bioactive IL-33 that in turn increased inflammatory chemokine and cytokine expression in activated Müller cells. Deletion of ST2, the IL-33 receptor α chain, or treatment with a soluble IL-33 decoy receptor significantly reduced release of inflammatory mediators from Müller cells, inhibited accumulation of mononuclear phagocytes in the outer retina, and protected photoreceptor rods and cones after a retina insult. This study demonstrates a central role for IL-33 in regulating mononuclear phagocyte recruitment to the photoreceptor layer and positions IL-33 signaling as a potential therapeutic target in macular degenerative diseases.
Amyloid-β dimers in the absence of plaque pathology impair learning and synaptic plasticity
Authors: Müller-Schiffmann Andreas , Herring Arne , Abdel-Hafiz Laila , Chepkova Aisa N. , Schäble Sandra , Wedel Diana , Horn Anselm H. C. , Sticht Heinrich , de Souza Silva Maria A. , Gottmann Kurt , Sergeeva Olga A. , Huston Joseph P. , Keyvani Kathy , Korth Carsten
Published: January 2016

Despite amyloid plaques, consisting of insoluble, aggregated amyloid-β peptides, being a defining feature of Alzheimer’s disease, their significance has been challenged due to controversial findings regarding the correlation of cognitive impairment in Alzheimer’s disease with plaque load. The amyloid cascade hypothesis defines soluble amyloid-β oligomers, consisting of multiple amyloid-β monomers, as precursors of insoluble amyloid-β plaques. Dissecting the biological effects of single amyloid-β oligomers, for example of amyloid-β dimers, an abundant amyloid-β oligomer associated with clinical progression of Alzheimer’s disease, has been difficult due to the inability to control the kinetics of amyloid-β multimerization. For investigating the biological effects of amyloid-β dimers, we stabilized amyloid-β dimers by an intermolecular disulphide bridge via a cysteine mutation in the amyloid-β peptide (Aβ-S8C) of the amyloid precursor protein. This construct was expressed as a recombinant protein in cells and in a novel transgenic mouse, termed tgDimer mouse. This mouse formed constant levels of highly synaptotoxic soluble amyloid-β dimers, but not monomers, amyloid-β plaques or insoluble amyloid-β during its lifespan. Accordingly, neither signs of neuroinflammation, tau hyperphosphorylation or cell death were observed. Nevertheless, these tgDimer mice did exhibit deficits in hippocampal long-term potentiation and age-related impairments in learning and memory, similar to what was observed in classical Alzheimer’s disease mouse models. Although the amyloid-β dimers were unable to initiate the formation of insoluble amyloid-β aggregates in tgDimer mice, after crossbreeding tgDimer mice with the CRND8 mouse, an amyloid-β plaque generating mouse model, Aβ-S8C dimers were sequestered into amyloid-β plaques, suggesting that amyloid-β plaques incorporate neurotoxic amyloid-β dimers that by themselves are unable to self-assemble. Our results suggest that within the fine interplay between different amyloid-β species, amyloid-β dimer neurotoxic signalling, in the absence of amyloid-β plaque pathology, may be involved in causing early deficits in synaptic plasticity, learning and memory that accompany Alzheimer’s disease.

10.1093/brain/awv355_video_abstract awv355_video_abstract
Detection of Chlamydia infection in Peromyscus species rodents from sylvatic and laboratory sources
Authors: Ramsey Kyle H. , Sigar Ira M. , Schripsema Justin H. , Townsend Kathryn E. , Barry Randall J. , Peters Jan , Platt Kenneth B.
Published: January 2016

To determine if Chlamydia muridarum, or other chlamydiae, are enzootic in rodents, we probed a serum bank of wild Peromyscus spp. mice for immunoglobulin G-antibody reactivity to ultraviolet light-inactivated C. muridarum elementary bodies (EBs) using an enzyme-linked immunoassay. Applying a cut-off for a positive reaction of OD405 nm = 0.1 at a 1:20 dilution, we found titratable antibody reactivity in 190 of 247 specimens surveyed (77%, mean OD405 = 0.33 ± 0.26, range = 0.11–1.81, median = 0.25). In addition, serum samples were obtained from a colony of specific pathogen-free Peromyscus spp. maintained at the University of South Carolina and six of 12 samples were reactive (50%, mean OD405 = 0.19 +/− 0.08, range = 0.1–0.32, median = 0.18). Lastly, 40 additional wild Peromyscus spp. were captured in a disparate region of Midwestern USA and 22 serum specimens were reactive (55%, mean OD405 = 0.22 +/− 0.11, range = 0.1–0.48, median = 0.2). Specificity of selected reactive sera for chlamydial antigen was confirmed on Western blot using resolved purified EBs as the detecting antigen. From tissues removed from several mice at necropsy, the gene for chlamydial 16S ribosomal ribonucleic acid (rRNA) was amplified by polymerase chain reaction (PCR). Positive samples of 16S rRNA were subjected to additional PCR for the major outer membrane protein gene (ompA). The amplicons of three select ompA positive samples were sequenced with ≥99% homology with C. muridarum. Our findings indicate that chlamydial infection is enzootic for Peromyscus spp., and that C. muridarum, or a closely related species or strain, is likely the agent in the tested rodent species.
Missed Opportunities to Diagnose Tuberculosis Are Common Among Hospitalized Patients and Patients Seen in Emergency Departments
Authors: Miller Aaron C. , Polgreen Linnea A. , Cavanaugh Joseph E. , Hornick Douglas B. , Polgreen Philip M.
Published: January 2016

Background.  Delayed diagnosis of tuberculosis (TB) may lead to worse outcomes and additional TB exposures.

Methods.  To estimate the potential number of misdiagnosed TB cases, we linked all hospital and emergency department (ED) visits in California′s Healthcare Cost and Utilization Project (HCUP) databases (2005–2011). We defined a potential misdiagnosis as a visit with a new, primary diagnosis of TB preceded by a recent respiratory-related hospitalization or ED visit. Next, we calculated the prevalence of potential missed TB diagnoses for different time windows. We also computed odds ratios (OR) comparing the likelihood of a previous respiratory diagnosis in patients with and without a TB diagnosis, controlling for patient and hospital characteristics. Finally, we determined the correlation between a hospital′s TB volume and the prevalence of potential TB misdiagnoses.

Results.  Within 30 days before an initial TB diagnosis, 15.9% of patients (25.7% for 90 days) had a respiratory-related hospitalization or ED visit. Also, within 30 days, prior respiratory-related visits were more common in patients with TB than other patients (OR = 3.83; P < .01), controlling for patient and hospital characteristics. Respiratory diagnosis-related visits were increasingly common until approximately 90 days before the TB diagnosis. Finally, potential misdiagnoses were more common in hospitals with fewer TB cases (ρ = −0.845; P < .01).

Conclusions.  Missed opportunities to diagnose TB are common and correlate inversely with the number of TB cases diagnosed at a hospital. Thus, as TB becomes infrequent, delayed diagnoses may increase, initiating outbreaks in communities and hospitals.
Knowledge, Attitude, and Practices of Healthcare Personnel Regarding the Transmission of Pathogens via Fomites at a Tertiary Care Hospital in Karachi, Pakistan
Authors: Aftab Hassaan Bin , Zia Bushra , Zahid Mohammad Faizan , Raheem Ahmed , Beg Mohammad Asim
Published: January 2016

Background.  Fomites are objects that can become colonized and serve as vectors in the transmission of pathogenic microorganisms. Literature examining the knowledge of healthcare personnel about this method of spread of infection is lacking. We conducted a study to assess the knowledge, attitude, and practices of healthcare personnel across different areas of patient care regarding the spread of infections at a tertiary care hospital in Karachi, Pakistan.

Methods.  A descriptive, cross-sectional study was conducted among healthcare personnel using a self-administered questionnaire. The questionnaire contained sections pertaining to demographic details and knowledge, attitude, and practices regarding fomites and their role in the transmission of pathogens.

Results.  Three hundred and fifty-three participants completed the questionnaire: 168 were male and 185 were female. Laboratory coats, stethoscopes, and bedside curtains were most frequently identified as fomites by the participants. Medical students had significantly lower mean scores in the knowledge and attitude sections than consultant physicians, resident physicians, and nurses. Nurses scored higher than consultant physicians, resident physicians, and medical students regarding practices that minimize fomite-borne spread of infections. 95% of the participants scored above 50% on the knowledge component of the questionnaire, but only 32.3% scored above 50% in the practices section.

Conclusions.  Our results show a large gap between the knowledge about fomites acting as vectors in the spread of pathogens and practices done to minimize this spread. Possessing adequate knowledge is ineffectual until and unless it is translated into the proper application of infection control practices. Incorporating awareness sessions and exercises into curricula are a reasonable way to raise awareness regarding this subject.
A Case of Long-Term Seronegative Human Immunodeficiency Virus (HIV) Infection: The Importance of the Humoral Response to HIV
Authors: Siemieniuk Reed A. C. , van der Meer Frank , van Marle Guido , Gill M. John
Published: January 2016

Background.  Seronegative human immunodeficiency virus (HIV) infections are exceedingly rare but might inform HIV-host physiology.

Methods.  We investigate the cause and consequences of a patient infected with HIV who did not mount a humoral response to HIV for 4 years.

Results.  The patient was confirmed HIV-uninfected by nucleic acid testing 4 months before rapidly progressing to acquired immune deficiency syndrome. The patient's humoral deficit was specific to HIV: he mounted robust humoral responses to all challenge vaccines including influenza A(H1N1)pdm09 and all T cell-dependent and -independent serotypes in the 23-valent pneumococcal polysaccharide vaccine. The virus had similar gp120 antigenicity to HIV-positive control serum as NL4-3 and YU2 prototype strains. Two human leukocyte antigen alleles associated with rapid progression were identified (B*08 and B*35), and a cytotoxic T-lymphocyte epitope site variant was noted: E277K. Viral decay (t1/2 ≈ 39 weeks) suggested that relatively long-lived cells were the source of ongoing viremia. Human immunodeficiency virus viremia was not suppressed until after the patient developed a humoral immune response, despite therapeutic antiretroviral levels. No resistance was detected by virtual phenotyping of virus obtained from serum or from gastrointestinal biopsies despite considerable antiretroviral selection pressure.

Conclusions.  Ineffective antibody production may be associated with a subgroup of extremely rapid HIV progressors. Although antiretroviral therapy may be sufficient to slow propagation of infection, it appears to be ineffective for HIV viral clearance in the absence of a humoral response.
Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1
Authors: Béguelin C. , Vázquez M. , Bertschi M. , Yerly S. , de Jong D. , Gutbrod K. , Rauch A. , Cusini A.
Published: January 2016

In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug-resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptoms.
Management of Multiple Myeloma Complicated by Hepatitis C Virus Reactivation: The Role of New Antiviral Therapy
Authors: Mahale Parag , Thomas Sheeba K. , Kyvernitakis Andreas , Torres Harrys A.
Published: January 2016

Reactivation of chronic hepatitis C virus (HCV) infection has been reported in cancer patients receiving chemotherapy. In this study, we report the first case, to our knowledge, of thalidomide-induced acute exacerbation and reactivation of chronic HCV infection complicating management of multiple myeloma. Sofosbuvir-based antiviral therapy helped achieve viral clearance and normalization of liver enzymes, thus allowing access to future potentially life-saving chemotherapy agents.
Senior Center-Based Hepatitis C Screening in Baltimore
Authors: Falade-Nwulia Oluwaseun , Irvin Risha , McAdams-Mahmoud Ayesha , Mehta Shruti H. , Niculescu Alexander , Lasola Jackline , Baker Dorcas , Eppel Arnold , Chaulk Patrick , Page Kathleen R. , Sulkowski Mark , Thomas David
Published: January 2016

Despite significant advancements in hepatitis C virus (HCV) treatments, the majority of individuals infected with HCV remain undiagnosed. We report on senior citizen center-based HCV testing in Baltimore, which revealed a 9.4% prevalence of infection. Our data suggest that community-based HCV testing and linkage to care in appropriate settings is feasible and high yield.
Embryo Localization Enhances the Survival of Acidovorax citrulli in Watermelon Seeds
Authors: Dutta Bhabesh , Schneider Raymond W. , Robertson Clark L. , Walcott Ronald R.
Published: January 2016

Acidovorax citrulli, the causal agent of bacterial fruit blotch (BFB) of cucurbits has been observed to survive for >34 years in stored melon and watermelon seeds. To better understand this remarkable longevity, we investigated the bacterium’s tolerance to desiccation and the effect of bacterial localization in different watermelon seed tissues on its survival. We compared the ability of A. citrulli to tolerate desiccation on filter paper discs and on host (watermelon) and nonhost (cabbage, corn and tomato) seeds to two seedborne (Xanthomonas campestris pv. campestris and Pantoea stewartii subsp. stewartii) and one soilborne (Ralstonia solanacearum) plant-pathogenic bacteria. A. citrulli survival on dry filter paper (>12 weeks) was similar to that of X. campestris pv. campestris but longer than P. stewartii subsp. stewartii. Ralstonia solanacearum survived longer than all other bacteria tested. On all seeds tested, A. citrulli and X. campestris pv. campestris populations declined by 5 orders of magnitude after 12 weeks of incubation at 4°C and 50% relative humidity, while R. solanacearum populations declined by 3 orders. P. stewartii subsp. stewartii was not recovered after 12 weeks of incubation. To determine the effect of tissue localization on bacterial survival, watermelon seeds infested with A. citrulli by flower stigma inoculation (resulting in bacterial localization in the embryo/endosperm) or by ovary pericarp inoculations (resulting in bacterial localization under the testa) were treated with peroxyacetic acid or chlorine (Cl2) gas. Following these treatments, a significantly higher reduction in BFB seed-to-seedling transmission was observed for seeds generated by ovary pericarp inoculation (≥89.5%) than for those generated by stigma inoculation (≤76.5%) (P < 0.05). Additionally, higher populations of A. citrulli survived when the bacteria were localized to the embryo/endosperm versus the seed coat, suggesting that tissue localization is important for bacterial survival in seed. This observation was confirmed when P. stewartii subsp. stewartii survived significantly longer in stigma-inoculated (embryo/endosperm-localized) watermelon seeds than in vacuum-infiltrated (testa-localized) seeds. Based on these results we conclude that A. citrulli cells are not intrinsically tolerant to desiccation and that localization of the bacterium to testa tissues does not enhance A. citrulli survival. In contrast, it is likely that embryo/endosperm localization enhances the survival of A. citrulli and other bacteria in seeds.
Genetically Divergent Types of the Wheat Leaf Fungus Puccinia triticina in Ethiopia, a Center of Tetraploid Wheat Diversity
Authors: Kolmer J. A. , Acevedo M. A.
Published: January 2016

Collections of Puccinia triticina, the wheat leaf rust fungus, were obtained from tetraploid and hexaploid wheat in the central highlands of Ethiopia, and a smaller number from Kenya, from 2011 to 2013, in order to determine the genetic diversity of this wheat pathogen in a center of host diversity. Single-uredinial isolates were derived and tested for virulence phenotype to 20 lines of Thatcher wheat that differ for single leaf rust resistance genes and for molecular genotypes with 10 simple sequence repeat (SSR) primers. Nine virulence phenotypes were described among the 193 isolates tested for virulence. Phenotype BBBQJ, found only in Ethiopia, was predominantly collected from tetraploid wheat. Phenotype EEEEE, also found only in Ethiopia, was exclusively collected from tetraploid wheat and was avirulent to the susceptible hexaploid wheat ‘Thatcher’. Phenotypes MBDSS and MCDSS, found in both Ethiopia and Kenya, were predominantly collected from common wheat. Phenotypes CCMSS, CCPSS, and CBMSS were found in Ethiopia from common wheat at low frequency. Phenotypes TCBSS and TCBSQ were found on durum wheat and common wheat in Kenya. Four groups of distinct SSR genotypes were described among the 48 isolates genotyped. Isolates with phenotypes BBBQJ and EEEEE were in two distinct SSR groups, and isolates with phenotypes MBDSS and MCDSS were in a third group. Isolates with CCMSS, CCPSS, CBMSS, TCBSS, and TCBSQ phenotypes were in a fourth SSR genotype group. The diverse host environment of Ethiopia has selected and maintained a genetically divergent population of P. triticina.
RNA1-Independent Replication and GFP Expression from Tomato marchitez virus Isolate M Cloned cDNA
Authors: Ferriol I. , Turina M. , Zamora-Macorra E. J. , Falk B. W.
Published: January 2016

Tomato marchitez virus (ToMarV; synonymous with Tomato apex necrosis virus) is a positive-strand RNA virus in the genus Torradovirus within the family Secoviridae. ToMarV is an emergent whitefly-transmitted virus that causes important diseases in tomato (Solanum lycopersicum) in Mexico. Here, the genome sequence of the ToMarV isolate M (ToMarV-M) was determined. We engineered full-length cDNA clones of the ToMarV-M genomic RNA (RNA1 and RNA2), separately, into a binary vector. Coinfiltration of both triggered systemic infections in Nicotiana benthamiana, tomato, and tomatillo (Physalis philadelphica) plants and recapitulated the biological activity of the wild-type virus. The viral progeny generated from tomato and tomatillo plants were transmissible by the whitefly Bemisia tabaci biotype B. Also, we assessed whether these infectious clones could be used for screening tomato cultivars for resistance to ToMarV and our results allowed us to differentiate resistant and susceptible tomato lines. We demonstrated that RNA1 of ToMarV-M is required for the replication of RNA2, and it can replicate independently of RNA2. From this, ToMarV-M RNA2 was used to express the green fluorescent protein in N. benthamiana plants, which allowed us to track cell-to-cell movement. The construction of full-length infectious cDNA clones of ToMarV-M provides an excellent tool to investigate virus–host–vector interactions and elucidate the functions of torradovirus-encoded proteins or the mechanisms of replication of torradovirus genomic RNA.
Surgical Correction of Scoliosis in Patients With Duchenne Muscular Dystrophy: 30-Year Experience
Authors: Scannell Brian P. , Yaszay Burt , Bartley Carrie E. , Newton Peter O. , Mubarak Scott J.
Published: January 2016

Background:

The natural history of scoliosis in Duchenne muscular dystrophy (DMD) is progressive and debilitating if neglected. The purpose of this study was to evaluate outcomes related to spinal deformity surgery in patients with DMD over a 30-year period.

Methods:

This was a single center retrospective study of all operatively treated scoliosis in DMD patients over 30 years. Minimum follow-up was 2 years. Owing to changes in instrumentation over time, patients were divided into 2 groups: Luque or pedicle screws (PS) constructs. Radiographic, perioperative variables, pulmonary function test (preoperatively and postoperatively), and complication data were evaluated.

Results:

There were 60 subjects (Luque: 47, PS: 13). The Luque group was on average 13 years old, 53 kg, and had 7 years of follow-up. Coronal Cobb was 31±12 degrees preoperatively, 16±11 degrees at first postoperatively, and 21±15 degrees at final follow-up (P≤0.001). Pelvic obliquity was 7±6 degrees preoperatively, 5±5 degrees at first postoperatively (P=0.43), and 5±4 degrees at final follow-up (P=0.77). The majority of this group was fused to L5 (45%) or the sacrum (49%). The PS group was on average 14 years old, 65 kg, and had 4 years of follow-up. Coronal Cobb was 43±19 degrees preoperatively, 12±9 degrees at first postoperatively (P≤0.001), and 12±8 degrees at final follow-up. Pelvic obliquity was 6±5 degrees preoperatively, 3±3 degrees at first postoperatively (P=0.06), and 2±2 degrees at final follow-up (P=0.053). The majority were fused to the pelvis (92%). Both groups’ pulmonary function declined with time. Both groups had high complication rates (Luque 68%; PS group 54%). The Luque group had more implant-related complications (26%); the PS group had a higher rate of early postoperative infections (23%).

Conclusions:

Over a 30-year period of operative treatment of scoliosis in DMD, both PS constructs and Luque instrumentation improved coronal Cobb. The PS group had improved and maintained pelvic obliquity. Both groups had high complication rates.

Level of Evidence:

Level IV—therapeutic.
Sacral Alar Iliac (SAI) Screws Fail 75% Less Frequently Than Iliac Screws in Neuromuscular Scoliosis
Authors: Shabtai Lior , Andras Lindsay M. , Portman Mark , Harris Liam R. , Choi Paul D. , Tolo Vernon T. , Skaggs David L.
Published: January 2016

Background:

Despite recent popularity of sacral alar iliac (SAI) screws for fusion to the pelvis for neuromuscular scoliosis, there are little data regarding the failure rate of this technique compared with traditional modes of iliac fixation. Theoretical advantages of the SAI screws are obviating the need for a rod to iliac screw connector and a lower implant profile. The purpose of this study is to determine whether SAI screws have fewer failures than iliac screws in neuromuscular scoliosis.

Methods:

Review of neuromuscular patients treated with posterior spinal fusion with pelvic fixation from 2004 to 2012 with minimum 2-year follow-up was conducted. Medical records and imaging studies were reviewed. Patients were divided into 2 groups based on the type of pelvic fixation (SAI or iliac screws), and implant failures were compared between the groups.

Results:

A total of 101 patients were reviewed, including 55 patients with iliac screws and 46 patients with SAI screws. Implant failures included: disengagement of the rod to iliac screw connector (10%, 10/101), separation of screw head from screw shaft (4%, 4/101), and set screw disengagement (2%, 2/101). The SAI group had a lower implant failure rate (7%, 3/46) compared with the iliac screw group (24%, 13/55) (P=0.031). Rod to iliac screw connectors failed in 18% (10/55) of patients. There were significantly less surgical revisions in the SAI group (2%, 1/46) for pelvic screw prominence compared with the iliac screw group (11%, 6/55) (P=0.027).

Conclusions:

SAI screws had a lower rate of implant failure and revision surgery compared with iliac screws. If rod to screw connector failures are excluded, the failure rate of SAI screws of 6.5% (3/46) is similar to that of iliac screws 5.5% (3/55); therefore, the most important advantage of the SAI technique may be obviating the need for a screw to rod connector.

Level of Evidence:

Level III.
Primary Debulking Surgery Versus Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer
Authors: Siesto Gabriele , Cavina Raffaele , Romano Fabrizio , Vitobello Domenico
Published: January 2016

Aims:

To compare the surgical and survival outcomes of patients undergoing primary debulking surgery (PDS) versus neoadjuvant chemotherapy (NACT) plus interval debulking surgery (IDS) for advanced epithelial ovarian cancer (EOC).

Materials and Methods:

Consecutive patients managed for advanced EOC since 2009 were matched through a propensity score analysis, defined as the probability of a woman having PDS or NACT plus IDS.

Results:

The study group consisted of 100 propensity-matched women receiving PDS or NACT plus IDS. Groups resulted homogeneous in terms of baseline characteristics and pathologic findings. Patients undergoing PDS had longer operative time (P=0.032) and more blood loss (P=0.011) than the counterpart receiving NACT. No differences were found in terms of residual disease (P=0.11), as well as in terms of hospitalization, intraoperative, and postoperative complications. The mean progression-free survival was 23.0 and 27.7 months (P=0.67), whereas the overall survival (OS) was 44.5 and 43.2 months (P=0.48) for the PDS and NACT plus IDS group, respectively. Residual disease (P<0.0001) was the only independent predictor of progression-free and OS at multivariate analysis.

Conclusions:

PDS and NACT plus IDS achieved comparable results in terms of progression-free and OS in patients with advanced EOC.
Albumin and Neutrophil-Lymphocyte Ratio (NLR) Predict Survival in Patients With Pancreatic Adenocarcinoma Treated With SBRT
Authors: Alagappan Muthuraman , Pollom Erqi L. , von Eyben Rie , Kozak Margaret M. , Aggarwal Sonya , Poultsides George A. , Koong Albert C. , Chang Daniel T.
Published: January 2016

Purpose:

To determine if pretreatment nutritional status and inflammatory markers correlate with survival in patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiotherapy (SBRT).

Materials and Methods:

We retrospectively reviewed 208 patients with newly diagnosed, locally advanced pancreatic adenocarcinoma treated with SBRT at our institution from 2002 to 2014. Laboratory values were collected before SBRT, including hemoglobin, platelets, albumin, red blood cell, white blood cell, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and tumor markers CA 19-9 and CEA. Patients were followed every 3 months with computed tomography (CT) and/or positron emission tomography-CT imaging to monitor for local recurrence and overall survival (OS).

Results:

Median follow-up after SBRT was 7.5 months (interquartile range, 4.6 to 12.0 mo) for all patients. Median OS for patients with NLR>5 compared with NLR≤5 was 6.9 and 8.5 months, respectively (P=0.0057). On univariate analysis, receipt of chemotherapy (P=0.05, hazard ratio [HR]=0.69), increased albumin (P=0.002, HR=0.64), increased red blood cell (P=0.05, HR=0.75), increased lymphocyte count (P=0.002, HR=0.66), decreased CEA (P=0.01, HR=0.96), and NLR≤5 (P=0.01, HR=0.65) correlated with improved OS. On multivariate analysis, higher albumin (P=0.03, HR=0.70), receipt of chemotherapy (P=0.007, HR=0.56), and NLR≤5 (P=0.02, HR=0.66) correlated with better survival.

Conclusions:

Preradiotherapy low albumin levels and NLR>5 correlate with decreased survival in patients with locally advanced pancreatic adenocarcinoma treated with SBRT, indicating the prognostic value of systemic inflammatory markers (such as NLR) and a role of nutritional supplementation to improve outcomes in these patients. Further investigation is warranted.
INTRAARTERIAL CHEMOTHERAPY FOR RETINOBLASTOMA IN A 2-MONTH-OLD INFANT
Authors: Magan Tejal , Khoo Chloe T.L. , Jabbour Pascal M. , Shields Carol L.
Published: January 2016

Purpose:

Intraarterial chemotherapy for retinoblastoma is usually reserved for infants aged 3 months or older because of the intricacy of the newborn vascular anatomy making the procedure technically challenging. The authors report a successful case of intraarterial chemotherapy performed in a 2-month-old infant using a minimal exposure approach.

Methods:

Case report.

Results:

A 2-month-old infant presented with leukocoria and was subsequently diagnosed with an exophytic Group D retinoblastoma in the right eye. The infant received melphalan 3 mg delivered into the ostium of the ophthalmic artery of the right eye under fluoroscopic guidance. Examination under anesthesia a month later showed complete tumor regression to a calcified Type I scar. After a second cycle of intraarterial chemotherapy, no further treatment was necessary. There were no complications.

Conclusion:

Intraarterial chemotherapy is generally used for retinoblastoma in infants aged 3 months or older. The patient was successfully catheterized and treated at 2 months of age, with complete tumor regression after a single chemotherapy dose. Thus, in expert hands, intraarterial chemotherapy can be considered in such young infants.
High-resolution Anorectal Manometry in Parkinson Disease With Defecation Disorder
Authors: Yu Ting , Wang Yun , Wu Gaojue , Xu Qinrong , Tang Yurong , Lin Lin
Published: January 2016

Goal:

To investigate the characteristics of high-resolution anorectal manometry (HR-ARM) in Parkinson disease (PD) patients with defecation disorder (DD) compared with patients with functional defecation disorder (FDD).

Background:

DD is a common gastrointestinal symptom in PD. HR-ARM is a relatively new and reliable method for detecting DD.

Study:

A cohort of PD patients with DD was matched with FDD patients. Defecatory symptoms were investigated by questionnaire. Anorectal motility and sensation were evaluated by HR-ARM. Differences in defecatory symptoms, sensorimotor parameters, and DD type were analyzed. Defecatory symptoms and manometric variables obtained in early-stage PD were compared with advanced stage, and relationships between manometric parameters and evacuatory symptoms explored.

Results:

Straining and sensation of blockage was experienced significantly more in PD than FDD, and stool consistency more severely affected. Maximum squeeze and intrarectal pressure during defecation in PD was lower than in FDD. Anal resting and residual pressures, duration of sustained squeeze, threshold volumes for first sensation, urgency, and maximum discomfort were similar between groups. PD patients presented predominantly with inadequate propulsive forces, whereas FDD patients showed dyssynergic defecation. Defecatory symptoms and manometric parameters did not differ between stages of PD.

Conclusions:

PD patients with DD experienced more straining and sensation of blockage than FDD patients, possibly related to inadequate anorectal motility and paradoxical anal contraction of pelvic floor. Impaired squeeze response and inadequate propulsive forces are specific to anorectal function of PD patients with DD, compared with FDD, with abnormalities unchanged between early and advanced PD.
Systemic Prophylactic Antibiotics for the Modified Introducer Method for Percutaneous Endoscopic Gastrostomy
Authors: Adachi Yasushi , Akino Kimishige , Mita Hiroaki , Kikuchi Takefumi , Yamashita Kentaro , Sasaki Yasushi , Arimura Yoshiaki , Endo Takao
Published: January 2016

Background:

Percutaneous endoscopic gastrostomy (PEG) is the most common method of enteral nutrition in patients who require long-term tube feeding. According to meta-analyses, administration of systemic prophylactic antibiotics for PEG reduces peristomal infection. However, with several recent developments in the procedure and instruments, the risk of infection might have been reduced. The aim of this study was to evaluate the use of systemic antibiotic prophylaxis for a modified introducer method of PEG.

Methods:

This prospective, randomized, double-blind trial assessed 278 patients undergoing PEG for inclusion. Ninety-one patients with an indication for PEG who gave informed consent to participate were randomized. Forty-six patients received prophylactic ampicillin and 45 patients received a placebo. A modified introducer method of PEG using a Seldinger PEG kit was performed. The primary outcome was the occurrence of clinically evident wound infection within 3 days after PEG.

Results:

Wound infection within 3 days was observed in none in the prophylaxis group and in 1 patient in the control group (P=0.4945). There was no significant difference between 2 groups in the other parameters, including peristomal infection within 7 days, overall infection, white blood cell counts, C-reactive protein level, and successive rate of finishing antibiotics.

Conclusions:

For wound infection within 3 days, noninferiority of the placebo group to the antibiotics group was preliminarily suggested with our criteria, but not for peristomal infection within 7 days. More strict criteria for noninferiority should be examined in a further large sample study.
Characteristics of Rib Fractures in Child Abuse—The Role of Low-Dose Chest Computed Tomography
Authors: Sanchez Thomas R. , Grasparil Angelo D. , Chaudhari Ruchir , Coulter Kevin P. , Wootton-Gorges Sandra L.
Published: January 2016

Objectives

Our aim is to describe the radiologic characteristics of rib fractures in clinically diagnosed cases of child abuse and suggest a complementary imaging for radiographically occult injuries in highly suspicious cases of child abuse.

Methods

Retrospective analysis of initial and follow-up skeletal surveys and computed tomography (CT) scans of 16 patients younger than 12 months were reviewed after obtaining approval from our institutional review board. The number, location, displacement, and age of the rib fractures were recorded.

Results

Out of a total 105 rib fractures, 84% (87/105) were detected on the initial skeletal survey. Seventeen percent (18/105) were seen only after follow-up imaging, more than half of which (11/18) were detected on a subsequent CT. Majority of the fractures were posterior (43%) and anterior (30%) in location. An overwhelming majority (96%) of the fractures are nondisplaced.

Conclusions

Seventeen percent of rib fractures analyzed in the study were not documented on the initial skeletal survey. Majority of fractures are nondisplaced and located posteriorly or anteriorly, areas that are often difficult to assess especially in the acute stage. The CT scan is more sensitive in evaluating these types of fractures. Low-dose chest CT can be an important imaging modality for suspicious cases of child abuse when initial radiographic findings are inconclusive.
Applying to Integrated Plastic Surgery Residency Programs: Trends in the Past 5 Years of the Match
Authors: Tadisina Kashyap Komarraju , Orra Susan , Bassiri Gharb Bahar , Kwiecien Grzegorz , Bernard Steven , Zins James E.
Published: January 2016

Background:

The average integrated plastic surgery applicant spends over $6000 for interviews. The average program director reviews over 200 applications per cycle. It is important to make the application process efficient and cost effective for both applicants and programs. The authors analyzed recent trends and the literature in an attempt to increase the likelihood that applicants match, suggest means of reducing applicants’ costs, and improve the process.

Methods:

A cross-sectional study of the National Residency Matching Program Charting Outcomes and results and data for the years 2009 to 2014 was performed. Applicant profile elements were examined for differences between matched/unmatched U.S. senior medical students. In addition, a literature review was performed.

Results:

The number of integrated plastic surgery positions rose from 69 in 2010 to 130 in 2014. Both matched and unmatched U.S. senior medical students have higher Step 2 scores, research and volunteer experiences, than 5 years ago. The likelihood of matching into an integrated plastic surgery residency has increased (2009, 52 percent; 2011, 44 percent; and 2014, 71 percent). Successful match rates were associated with Alpha Omega Alpha status and graduating from a top-40 ranked medical school (p < 0.05). Applicants with a lower number of ranked programs had increased match rates in 2014 than in previous years. Literature review revealed that program directors also value strong recommendation letters, publications, persistent work ethic (“grit”), away rotations, and an accurate curriculum vitae.

Conclusions:

Within the setting of increased applicant competitiveness, the authors recommend maximizing subjective qualities in order to differentiate themselves from a highly eligible applicant pool. In addition, applicants should diversify the types of programs at which they interview to maximize their chances of matching.
The Potential of Twitter as a Data Source for Patient Safety
Authors: Nakhasi Atul , Bell Sarah G. , Passarella Ralph J. , Paul Michael J. , Dredze Mark , Pronovost Peter J.
Published: January 2016

Background

Error-reporting systems are widely regarded as critical components to improving patient safety, yet current systems do not effectively engage patients. We sought to assess Twitter as a source to gather patient perspective on errors in this feasibility study.

Methods

We included publicly accessible tweets in English from any geography. To collect patient safety tweets, we consulted a patient safety expert and constructed a set of highly relevant phrases, such as “doctor screwed up.” We used Twitter’s search application program interface from January to August 2012 to identify tweets that matched the set of phrases. Two researchers used criteria to independently review tweets and choose those relevant to patient safety; a third reviewer resolved discrepancies. Variables included source and sex of tweeter, source and type of error, emotional response, and mention of litigation.

Results

Of 1006 tweets analyzed, 839 (83%) identified the type of error: 26% of which were procedural errors, 23% were medication errors, 23% were diagnostic errors, and 14% were surgical errors. A total of 850 (84%) identified a tweet source, 90% of which were by the patient and 9% by a family member. A total of 519 (52%) identified an emotional response, 47% of which expressed anger or frustration, 21% expressed humor or sarcasm, and 14% expressed sadness or grief. Of the tweets, 6.3% mentioned an intent to pursue malpractice litigation.

Conclusions

Twitter is a relevant data source to obtain the patient perspective on medical errors. Twitter may provide an opportunity for health systems and providers to identify and communicate with patients who have experienced a medical error. Further research is needed to assess the reliability of the data.
Does Physician's Training Induce Overconfidence That Hampers Disclosing Errors?
Authors: Brezis Mayer , Orkin-Bedolach Yael , Fink Daniel , Kiderman Alexander
Published: January 2016

Purpose

Although transparency is critical for reducing medical errors, physicians feel discomfort with disclosure. We explored whether overconfidence relates to physician's reluctance to admit that an error may have occurred.

Method

At 3 university medical centers, a survey presented a clinical vignette of a girl with urinary infection and penicillin allergy to medical students and physicians, asking them to rate their level of confidence for each step of the diagnosis and management. After anaphylaxis develops after cephalosporin administration, respondents were asked about their willingness to admit that an error might have occurred and to rate their level of discomfort in doing so. We analyzed levels of confidence, accuracy, willingness to admit mistake, and discomfort.

Results

Respondents reported high levels of confidence for their answers to the questions of diagnosis and management, even when wrong—indicating miscalibration of confidence and accuracy. Compared with students, physicians had significantly higher levels of confidence, lower accuracy, and lower willingness to admit mistake. Although most respondents agreed in principle that errors should be disclosed, in the presented case, significantly less agreed to admit that a mistake might have occurred or to say so explicitly to the family. An association was found between overconfidence and discomfort with disclosure.

Conclusions

Our study shows overconfidence associated with clinician's training and with reluctance to admit mistake, suggesting a contributing role to the difficulty in leveraging safety events into quality improvement. Training physicians to have both knowledge and adequate self-doubt is an educational challenge.
A Systems Approach to Analyzing and Preventing Hospital Adverse Events
Authors: Leveson Nancy , Samost Aubrey , Dekker Sidney , Finkelstein Stan , Raman Jai
Published: January 2016

Objective

This study aimed to demonstrate the use of a systems theory-based accident analysis technique in health care applications as a more powerful alternative to the chain-of-event accident models currently underpinning root cause analysis methods.

Method

A new accident analysis technique, CAST [Causal Analysis based on Systems Theory], is described and illustrated on a set of adverse cardiovascular surgery events at a large medical center. The lessons that can be learned from the analysis are compared with those that can be derived from the typical root cause analysis techniques used today.

Results

The analysis of the 30 cardiovascular surgery adverse events using CAST revealed the reasons behind unsafe individual behavior, which were related to the design of the system involved and not negligence or incompetence on the part of individuals. With the use of the system-theoretic analysis results, recommendations can be generated to change the context in which decisions are made and thus improve decision making and reduce the risk of an accident.

Conclusions

The use of a systems-theoretic accident analysis technique can assist in identifying causal factors at all levels of the system without simply assigning blame to either the frontline clinicians or technicians involved. Identification of these causal factors in accidents will help health care systems learn from mistakes and design system-level changes to prevent them in the future.