bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Genes Periodically Expressed in the Human Cell Cycle and Their Expression in Tumors
Authors: Whitfield Michael L. , Sherlock Gavin , Saldanha Alok J. , Murray John I. , Ball Catherine A. , Alexander Karen E. , Matese John C. , Perou Charles M. , Hurt Myra M. , Brown Patrick O. , Botstein David
Published: September 2016

The genome-wide program of gene expression during the cell division cycle in a human cancer cell line (HeLa) was characterized using cDNA microarrays. Transcripts of >850 genes showed periodic variation during the cell cycle. Hierarchical clustering of the expression patterns revealed coexpressed groups of previously well-characterized genes involved in essential cell cycle processes such as DNA replication, chromosome segregation, and cell adhesion along with genes of uncharacterized function. Most of the genes whose expression had previously been reported to correlate with the proliferative state of tumors were found herein also to be periodically expressed during the HeLa cell cycle. However, some of the genes periodically expressed in the HeLa cell cycle do not have a consistent correlation with tumor proliferation. Cell cycle-regulated transcripts of genes involved in fundamental processes such as DNA replication and chromosome segregation seem to be more highly expressed in proliferative tumors simply because they contain more cycling cells. The data in this report provide a comprehensive catalog of cell cycle regulated genes that can serve as a starting point for functional discovery. The full dataset is available at http://genome-www.stanford.edu/Human-CellCycle/HeLa/ .
Dissociation of the Tubulin Dimer Is Extremely Slow, Thermodynamically Very Unfavorable, and Reversible in the Absence of an Energy Source
Authors: Caplow Michael , Fee Lanette
Published: September 2016

The finding that exchange of tubulin subunits between tubulin dimers (α-β + α′β′ ↔ α′β + αβ′) does not occur in the absence of protein cofactors and GTP hydrolysis conflicts with the assumption that pure tubulin dimer and monomer are in rapid equilibrium. This assumption underlies the many physical chemical measurements of the Kdfor dimer dissociation. To resolve this discrepancy we used surface plasmon resonance to determine the rate constant for dimer dissociation. The half-time for dissociation was ∼9.6 h with tubulin-GTP, 2.4 h with tubulin-GDP, and 1.3 h in the absence of nucleotide. AKdequal to 10−11M was calculated from the measured rate for dissociation and an estimated rate for association. Dimer dissociation was found to be reversible, and dimer formation does not require GTP hydrolysis or folding information from protein cofactors, because 0.2 μM tubulin-GDP incubated for 20 h was eluted as dimer when analyzed by size exclusion chromatography. Because 20 h corresponds to eight half-times for dissociation, only monomer would be present if dissociation were an irreversible reaction and if dimer formation required GTP or protein cofactors. Additional evidence for a 10−11M Kdwas obtained from gel exclusion chromatography studies of 0.02–2 nM tubulin-GDP. The slow dissociation of the tubulin dimer suggests that protein tubulin cofactors function to catalyze dimer dissociation, rather than dimer assembly. Assuming N-site-GTP dissociation is from monomer, our results agree with the 16-h half-time for N-site GTP in vitro and 33 h half-life for tubulin N-site-GTP in CHO cells.
TOR and paradigm change: cell growth is controlled
Authors: Hall Michael N.
Published: September 2016

This year marks the 25th anniversary of the discovery of target of rapamycin (TOR), a highly conserved kinase and central controller of cell growth. In this Retrospective, I briefly describe the discovery of TOR and the subsequent elucidation of its cellular role. I place particular emphasis on an article by Barbet et al. from 1996, the first suggesting that TOR controls cell growth in response to nutrients.
A mitotic nuclear envelope tether for Gle1 also affects nuclear and nucleolar architecture
Authors: Chemudupati Mahesh , Osmani Aysha H. , Osmani Stephen A.
Published: September 2016

During Aspergillus nidulans mitosis, peripheral nuclear pore complex (NPC) proteins (Nups) disperse from the core NPC structure. Unexpectedly, one predicted peripheral Nup, Gle1, remains at the mitotic nuclear envelope (NE) via an unknown mechanism. Gle1 affinity purification identified mitotic tether for Gle1 (MtgA), which tethers Gle1 to the NE during mitosis but not during interphase when Gle1 is at NPCs. MtgA is the orthologue of the Schizosaccharomyces pombe telomere-anchoring inner nuclear membrane protein Bqt4. Like Bqt4, MtgA has meiotic roles, but it is functionally distinct from Bqt4 because MtgA is not required for tethering telomeres to the NE. Domain analyses showed that MtgA targeting to the NE requires its C-terminal transmembrane domain and a nuclear localization signal. Of importance, MtgA functions beyond Gle1 mitotic targeting and meiosis and affects nuclear and nucleolar architecture when deleted or overexpressed. Deleting MtgA generates small, round nuclei, whereas overexpressing MtgA generates larger nuclei with altered nuclear compartmentalization resulting from NE expansion around the nucleolus. The accumulation of MtgA around the nucleolus promotes a similar accumulation of the endoplasmic reticulum (ER) protein Erg24, reducing its levels in the ER. This study extends the functions of Bqt4-like proteins to include mitotic Gle1 targeting and modulation of nuclear and nucleolar architecture.
Increased Dietary Salt Changes Baroreceptor Sensitivity and Intrarenal Renin–Angiotensin System in Goldblatt Hypertension
Authors: Shimoura Caroline G. , Lincevicius Gisele S. , Nishi Erika E. , Girardi Adriana C. C. , Simon Karin A. , Bergamaschi Cassia T. , Campos Ruy R.
Published: September 2016

BACKGROUND

Renovascular hypertension (2-kidney 1-clip model (2K1C)) is characterized by renin–angiotensin system (RAS) activation. Increased Angiotensin II (AngII) leads to sympathoexcitation, oxidative stress, and alterations in sodium and water balance.

AIM

The aim of this study was to evaluate whether a discrete increase in sodium chloride intake in 2K1C rats leads to changes in cardiovascular and autonomic function, oxidative stress, and renin angiotensin aldosterone system.

METHODS

After 4 weeks of induction of hypertension, rats were fed a normal sodium diet (0.4% NaCl) or a high-sodium diet (2% NaCl) for 2 consecutive weeks. Experiments were carried out for 6 weeks after clipping. Mean arterial pressure (MAP), renal sympathetic nerve activity (rSNA), arterial baroreflex control of rSNA, and heart rate (HR) were assessed. Thiobarbituric acid reactive substances and glutathione were measured as indicators of systemic oxidative stress. Angiostensin-converting enzyme (ACE), ACE2, and angiotensinogen were evaluated in clipped and unclipped kidneys as also urinary angiotensinogen and plasma renin activity. Angiotensinogen, plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) and ACE2 in clipped and unclipped kidneys were evaluated.

RESULTS

High-sodium diet did not change systemic oxidative stress, and basal values of MAP, HR, or rSNA; however, increased renal (−0.7±0.2 vs. −1.5±0.1 spikes/s/mm Hg) and cardiac (−0.9±0.14 vs. −1.5±0.14 bpm/mm Hg) baroreceptor reflex sensitivity in 2K1C rats. Although there was no alteration in PRA, a high-salt diet significantly decreased urinary angiotensinogen, ACE, and ACE2 expressions in the clipped and unclipped kidneys.

CONCLUSIONS

Increased arterial baroreceptor control associated with a suppression of the intrarenal RAS in the 2K1C rats on high-salt diet provide a salt-resistant effect on hypertension and sympathoexcitation in renovascular hypertensive rats.
Studies on Quality of Potato Flour Blends with Rice Flour for Making Extruded Noodles
Authors: Wang Li , Guo Jingxuan , Wang Ren , Shen Cunkuan , Li Yongfu , Luo Xiaohu , Li Yanan , Chen Zhengxing
Published: September 2016

The effects of rice flour on the physicochemical properties of the raw material system and the quality of extruded potato–rice noodles were studied. The results demonstrated that the amylose content, pasting viscosities, storage modulus (G′), and loss modulus (G″) gradually increased with the included levels of rice flour, whereas the swelling power, solubility, and pasting temperature decreased with increasing rice flour content. The extruded potato–rice noodles exhibited desirable cooking qualities and textural properties with rice flour contents of up to 40%. Additionally, sensory evaluations revealed that the scores for chewiness, firmness, slipperiness, elasticity, and overall acceptability increased gradually with increasing rice flour content in the blends. Additionally, the results indicated the possibility of replacing potato flour with rice flour at a ratio of 6:4 to produce extruded potato–rice noodles of acceptable quality.
Human Albumin Use in Adults in U.S. Academic Medical Centers
Authors: Suarez Jose I. , Martin Renee H. , Hohmann Samuel F. , Calvillo Eusebia , Bershad Eric M. , Venkatasubba Rao Chethan P. , Georgiadis Alexandros , Flower Oliver , Zygun David , Finfer Simon
Published: September 2016

Objective:

To determine rates and predictors of albumin administration, and estimated costs in hospitalized adults in the United States.

Design:

Cohort study of adult patients from the University HealthSystem Consortium database from 2009 to 2013.

Setting:

One hundred twenty academic medical centers and 299 affiliated hospitals.

Patients:

A total of 12,366,264 hospitalization records.

Interventions:

Analysis of rates and predictors of albumin administration, and estimated costs.

Measurements and Main Results:

Overall the proportion of admissions during which albumin was administered increased from 6.2% in 2009 to 7.5% in 2013; absolute difference 1.3% (95% CI, 1.30–1.40%; p < 0.0001). The increase was greater in surgical patients from 11.7% in 2009 to 15.1% in 2013; absolute difference 3.4% (95% CI, 3.26–3.46%; p < 0.0001). Albumin use varied geographically being lowest with no increase in hospitals in the North Eastern United States (4.9% in 2009 and 5.3% in 2013) and was more common in bigger (> 750 beds; 5.2% in 2009 and 7.3% in 2013) compared to smaller hospitals (< 250 beds; 4.4% in 2009 to 6.2% in 2013). Factors independently associated with albumin use were appropriate indication for albumin use (odds ratio, 65.220; 95% CI, 62.459–68.103); surgical admission (odds ratio, 7.942; 95% CI, 7.889–7.995); and high severity of illness (odds ratio, 8.933; 95% CI, 8.825–9.042). Total estimated albumin cost significantly increased from $325 million in 2009 to $468 million in 2013; (absolute increase of $233 million), p value less than 0.0001.

Conclusions:

The proportion of hospitalized adults in the United States receiving albumin has increased, with marked, and currently unexplained, geographic variability and variability by hospital size.
Human Sepsis Eicosanoid and Proresolving Lipid Mediator Temporal Profiles: Correlations With Survival and Clinical Outcomes
Authors: Dalli Jesmond , Colas Romain A. , Quintana Carolina , Barragan-Bradford Diana , Hurwitz Shelley , Levy Bruce D. , Choi Augustine M. , Serhan Charles N. , Baron Rebecca M.
Published: September 2016

Objective:

To identify and measure recently described chemical mediators, termed specialized pro-resolving mediators that actively regulate the resolution of acute-inflammation, and correlate measurements with clinical outcomes.

Design:

Herein, deidentified plasma was collected from sepsis patients (n = 22 subjects) within 48 hours of admission to the ICU and on days 3 and 7 thereafter and subjected to lipid mediator profiling.

Setting:

Brigham and Women’s Hospital Medical Intensive Care Unit.

Subjects:

Patients in the medical ICU with sepsis.

Measurements and Main Results:

In all patients, we identified more than 30 bioactive mediators and pathway markers in peripheral blood using established criteria for arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid metabolomes. These included inflammation initiating mediators leukotriene B4 and prostaglandin E2 and pro-resolving mediators resolvin D1, resolvin D2, and protectin D1. In sepsis nonsurvivors, we found significantly higher inflammation-initiating mediators including prostaglandin F2α and leukotriene B4 and pro-resolving mediators, including resolvin E1, resolvin D5, and 17R-protectin D1 than was observed in surviving sepsis subjects. This signature was present at ICU admission and persisted for 7 days. Further analysis revealed increased respiratory failure in nonsurvivors. Higher inflammation-initiating mediators (including prostaglandin F2α) and select proresolving pathways were associated with the development of acute respiratory distress syndrome, whereas other traditional clinical indices were not predictive of acute respiratory distress syndrome development.

Conclusions:

These results provide peripheral blood lipid mediator profiles in sepsis that correlate with survival and acute respiratory distress syndrome development, thus suggesting plausible novel biomarkers and biologic targets for critical illness.
Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia
Authors: Fitzgerald Julie C. , Weiss Scott L. , Maude Shannon L. , Barrett David M. , Lacey Simon F. , Melenhorst J. Joseph , Shaw Pamela , Berg Robert A. , June Carl H. , Porter David L. , Frey Noelle V. , Grupp Stephan A. , Teachey David T.
Published: September 2016

Objective:

Initial success with chimeric antigen receptor–modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnosis, prognosis, and therapy. We sought to characterize the timing, severity, and intensive care management of cytokine release syndrome after chimeric antigen receptor–modified T cell therapy.

Design:

Retrospective cohort study.

Setting:

Academic children’s hospital.

Patients:

Thirty-nine subjects with relapsed/refractory acute lymphoblastic leukemia treated with chimeric antigen receptor–modified T cell therapy on a phase I/IIa clinical trial (ClinicalTrials.gov number NCT01626495).

Interventions:

All subjects received chimeric antigen receptor–modified T cell therapy. Thirteen subjects with cardiovascular dysfunction were treated with the interleukin-6 receptor antibody tocilizumab.

Measurements and Main Results:

Eighteen subjects (46%) developed grade 3–4 cytokine release syndrome, with prolonged fever (median, 6.5 d), hyperferritinemia (median peak ferritin, 60,214 ng/mL), and organ dysfunction. Fourteen (36%) developed cardiovascular dysfunction treated with vasoactive infusions a median of 5 days after T cell therapy. Six (15%) developed acute respiratory failure treated with invasive mechanical ventilation a median of 6 days after T cell therapy; five met criteria for acute respiratory distress syndrome. Encephalopathy, hepatic, and renal dysfunction manifested later than cardiovascular and respiratory dysfunction. Subjects had a median of 15 organ dysfunction days (interquartile range, 8–20). Treatment with tocilizumab in 13 subjects resulted in rapid defervescence (median, 4 hr) and clinical improvement.

Conclusions:

Grade 3–4 cytokine release syndrome occurred in 46% of patients following T cell therapy for relapsed/refractory acute lymphoblastic leukemia. Clinicians should be aware of expanding use of this breakthrough therapy and implications for critical care units in cancer centers.
Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome
Authors: Mira Juan C. , Gentile Lori F. , Mathias Brittany J. , Efron Philip A. , Brakenridge Scott C. , Mohr Alicia M. , Moore Frederick A. , Moldawer Lyle L.
Published: September 2016

Objectives:

To provide an appraisal of the evolving paradigms in the pathophysiology of sepsis and propose the evolution of a new phenotype of critically ill patients, its potential underlying mechanism, and its implications for the future of sepsis management and research.

Design:

Literature search using PubMed, MEDLINE, EMBASE, and Google Scholar.

Measurements and Main Results:

Sepsis remains one of the most debilitating and expensive illnesses, and its prevalence is not declining. What is changing is our definition(s), its clinical course, and how we manage the septic patient. Once thought to be predominantly a syndrome of over exuberant inflammation, sepsis is now recognized as a syndrome of aberrant host protective immunity. Earlier recognition and compliance with treatment bundles has fortunately led to a decline in multiple organ failure and in-hospital mortality. Unfortunately, more and more sepsis patients, especially the aged, are suffering chronic critical illness, rarely fully recover, and often experience an indolent death. Patients with chronic critical illness often exhibit “a persistent inflammation-immunosuppression and catabolism syndrome,” and it is proposed here that this state of persisting inflammation, immunosuppression and catabolism contributes to many of these adverse clinical outcomes. The underlying cause of inflammation-immunosuppression and catabolism syndrome is currently unknown, but there is increasing evidence that altered myelopoiesis, reduced effector T-cell function, and expansion of immature myeloid-derived suppressor cells are all contributory.

Conclusions:

Although newer therapeutic interventions are targeting the inflammatory, the immunosuppressive, and the protein catabolic responses individually, successful treatment of the septic patient with chronic critical illness and persistent inflammation-immunosuppression and catabolism syndrome may require a more complementary approach.
Evaluation of RBC Transfusion Practice in Adult ICUs and the Effect of Restrictive Transfusion Protocols on Routine Care
Authors: Seitz Kevin P. , Sevransky Jonathan E. , Martin Greg S. , Roback John D. , Murphy David J.
Published: September 2016

Objective:

Research supports the efficacy and safety of restrictive transfusion protocols to reduce avoidable RBC transfusions, but evidence of their effectiveness in practice is limited. This study assessed whether admission to an ICU with an restrictive transfusion protocol reduces the likelihood of transfusion for adult patients.

Design:

Observational study using data from the multicenter, cohort Critical Illness Outcomes Study. Patient-level analyses were conducted with RBC transfusion on day of enrollment as the outcome and admission to an ICU with a restrictive transfusion protocol as the exposure of interest. Covariates included demographics, hospital course (e.g., lowest hematocrit, blood loss), severity of illness (e.g., Sequential Organ Failure Assessment score), interventions (e.g., sedation/analgesia), and ICU characteristics (e.g., size). Multivariable logistic regression modeling assessed the independent effects of restrictive transfusion protocols on transfusions.

Setting:

Fifty-nine U.S. ICUs.

Patients:

A total of 6,027 adult ICU patients.

Interventions:

None.

Measurements and Main Results:

Of the 59 study ICUs, 24 had an restrictive transfusion protocol; 2,510 patients (41.6%) were in an ICU with an restrictive transfusion protocol. The frequency of RBC transfusion among patients with severe (hematocrit, < 21%), moderate (hematocrit, 21–30%), and mild (hematocrit, > 30%) anemia in restrictive transfusion protocol ICUs was 67%, 19%, and 4%, respectively, compared with 60%, 14%, and 2% for those in ICUs without an restrictive transfusion protocol. Only 27% of transfusions were associated with a hematocrit less than 21%. Adjusting for confounding factors, restrictive transfusion protocols independently reduced the odds of transfusion in moderate anemia with an odds ratio of 0.59 (95% CI, 0.36–0.96) while demonstrating no effect in mild (p= 0.93) or severe (p= 0.52) anemia.

Conclusions:

In this sample of ICU patients, transfusions often occurred outside evidence-based guidelines, but admission to an ICU with an restrictive transfusion protocol did reduce the risk of transfusion in moderately anemic patients controlling for patient and ICU factors. This study supports the effectiveness of restrictive transfusion protocols for influencing transfusions in clinical practice.
Opening the Door: The Experience of Chronic Critical Illness in a Long-Term Acute Care Hospital
Authors: Lamas Daniela J. , Owens Robert L. , Nace R. Nicholas , Massaro Anthony F. , Pertsch Nathan J. , Gass Jonathon , Bernacki Rachelle E. , Block Susan D.
Published: September 2016

Objective:

Chronically critically ill patients have recurrent infections, organ dysfunction, and at least half die within 1 year. They are frequently cared for in long-term acute care hospitals, yet little is known about their experience in this setting. Our objective was to explore the understanding and expectations and goals of these patients and surrogates.

Design:

We conducted semi-structured interviews with chronically critically ill long-term acute care hospital patients or surrogates. Conversations were recorded, transcribed, and analyzed.

Setting:

One long-term acute care hospital.

Subjects:

Chronically critically ill patients, defined by tracheotomy for prolonged mechanical ventilation, or surrogates.

Intervention:

Semi-structured conversation about quality of life, expectations, and planning for setbacks.

Measurements and Main Results:

A total of 50 subjects (30 patients and 20 surrogates) were enrolled. Thematic analyses demonstrated: 1) poor quality of life for patients; 2) surrogate stress and anxiety; 3) optimistic health expectations; 4) poor planning for medical setbacks; and 5) disruptive care transitions. Nearly 80% of patient and their surrogate decision makers identified going home as a goal; 38% were at home at 1 year.

Conclusions:

Our study describes the experience of chronically critically ill patients and surrogates in an long-term acute care hospital and the feasibility of patient-focused research in this setting. Our findings indicate overly optimistic expectations about return home and unmet palliative care needs, suggesting the need for integration of palliative care within the long-term acute care hospital. Further research is also needed to more fully understand the challenges of this growing population of ICU survivors.
Single Session Treatment of Rolling Acne Scars Using Tumescent Anesthesia, 20% Trichloracetic Acid Extensive Subcision, and Fractional CO2 Laser
Authors: Taylor Mark B. , Zaleski-Larsen Lisa , McGraw Timothy A.
Published: September 2016

BACKGROUND

Successful treatment of acne scars is challenging. Many modalities have been used with marginal success.

OBJECTIVE

The authors describe a combination of a superficial chemical peel, subcision, and fractional carbon dioxide (CO2) laser resurfacing in a single-treatment session as a novel treatment approach for rolling acne scars.

METHODS

A total of 114 patients (75 women and 39 men) with predominantly rolling acne scars were treated with a 20% trichloracetic acid chemical peel, subcision with a novel dissecting instrument, and the CO2laser under tumescent anesthesia. This was a retrospective, uncontrolled, unblinded study.

RESULTS

The mean improvement after a single treatment was 2.9 on a scale of 1 to 4 with few complications. Ninety percent of the patients were satisfied with their final result and desired no additional treatment.

CONCLUSION

The combination of a trichloracetic acid 20% chemical peel, subcision, and fractional CO2laser resurfacing combined with tumescent anesthesia is both safe and effective in the treatment of rolling acne scars.
Variable Linezolid Exposure in Intensive Care Unit Patients—Possible Role of Drug–Drug Interactions
Authors: Töpper Christoph , Steinbach Cathérine L. , Dorn Christoph , Kratzer Alexander , Wicha Sebastian G. , Schleibinger Michael , Liebchen Uwe , Kees Frieder , Salzberger Bernd , Kees Martin G.
Published: September 2016

Background:

Standard doses of linezolid may not be suitable for all patient groups. Intensive care unit (ICU) patients in particular may be at risk of inadequate concentrations. This study investigated variability of drug exposure and its potential sources in this population.

Methods:

Plasma concentrations of linezolid were determined by high-performance liquid chromatography in a convenience sample of 20 ICU patients treated with intravenous linezolid 600 mg twice daily. Ultrafiltration applying physiological conditions (pH 7.4/37°C) was used to determine the unbound fraction. Individual pharmacokinetic (PK) parameters were estimated by population PK modeling. As measures of exposure to linezolid, area under the concentration–time curve (AUC) and trough concentrations (Cmin) were calculated and compared with published therapeutic ranges (AUC 200–400 mg*h/L, Cmin 2–10 mg/L). Coadministered inhibitors or inducers of cytochrome P450 and/or P-glycoprotein were noted.

Results:

Data from 18 patients were included into the PK evaluation. Drug exposure was highly variable (median, range: AUC 185, 48–618 mg*h/L, calculated Cmin 2.92, 0.0062–18.9 mg/L), and only a minority of patients had values within the target ranges (6 and 7, respectively). AUC and Cmin were linearly correlated (R = 0.98), and classification of patients (underexposed/within therapeutic range/overexposed) according to AUC or Cmin was concordant in 15 cases. Coadministration of inhibitors was associated with a trend to higher drug exposure, whereas 3 patients treated with levothyroxine showed exceedingly low drug exposure (AUC ∼60 mg*h/L, Cmin <0.4 mg/L). The median unbound fraction in all 20 patients was 90.9%.

Conclusions:

Drug exposure after standard doses of linezolid is highly variable and difficult to predict in ICU patients, and therapeutic drug monitoring seems advisable. PK drug–drug interactions might partly be responsible and should be further investigated; protein binding appears to be stable and irrelevant.
A RESCUE THERAPY FOR PERSISTENT OPTIC DISK PIT MACULOPATHY IN PREVIOUSLY VITRECTOMIZED EYES
Authors: Figueroa Marta S. , Nadal Jeroni , Contreras Inés
Published: September 2016

Purpose:

To report the results of vitrectomy with platelet-rich plasma (PRP) application and gas tamponade as a rescue therapy in previously vitrectomized eyes with optic disk pit (ODP) maculopathy.

Methods:

Three patients with visual loss due to persistent or recurrent ODP maculopathy who had undergone previous vitrectomy were offered application of PRP. Platelet-rich plasma was obtained by centrifugation of a blood sample from each patient. Surgery consisted of vitrectomy and internal limiting membrane peeling if the membrane had not been already removed (in two eyes). After fluid/air exchange, three drops of PRP were applied on the ODP followed by 8% C3F8 tamponade. Immediately after surgery, the patient remained supine for 30 minutes and then kept a face-down position for 2 weeks.

Results:

Optic disk pit maculopathy improved as soon as two weeks after surgery and resolved in all eyes between six and eight months after PRP application. Patients were followed up for three years, with no recurrences. Visual acuity remained stable in one eye and improved in two eyes.

Conclusion:

Vitrectomy with PRP application may be useful as a rescue therapy in patients with refractory ODP maculopathy. Platelet-rich plasma may act by promoting the closure of the communication between the vitreous and the intraretinal/subretinal space at the pit. This treatment may avoid potentially harmful maneuvers that have been used to treat ODP maculopathy.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF A29 BIRDSHOT CHORIORETINOPATHY COMPLICATED BY RETINAL NEOVASCULARIZATION
Authors: Phasukkijwatana Nopasak , Iafe Nicholas , Sarraf David
Published: September 2016

Purpose:

To describe the quantitative optical coherence tomography angiography analysis of the superficial and deep retinal capillary plexus in a case of A29 birdshot chorioretinopathy (BCR) complicated by retinal neovascularization.

Methods:

Multimodal retinal imaging, including optical coherence tomography angiography with quantitated vessel density analysis of the superficial and deep retinal capillary plexus, was performed in a case of A29 BCR. Capillary density (mm−1) was defined as the total vessel length (mm) per area (mm2).

Results:

A 39-year-old healthy white man presented with vitreous hemorrhage and retinal neovascularization at baseline. Clinical presentation was consistent with BCR and human leukocyte antigen testing confirmed A29 positivity. Optical coherence tomography angiography was performed 6 years after the diagnosis and revealed capillary density reduction in the superficial and especially in the deep retinal capillary plexus. Quantitative vessel density analysis was compared with the mean capillary density of 11 age-matched normal eyes and demonstrated 6% and 18% reduction of the superficial plexus in the right and left eyes of our patient, respectively. For the deep plexus, a reduction of 25% and 32% was found in the right and left eyes, respectively.

Conclusion:

In this patient with BCR, capillary density reduction was most marked at the deep retinal capillary plexus level and may explain the development of retinal neovascularization in this case. Quantitative optical coherence tomography angiography may be a useful tool to study and to monitor retinal microvascular changes in patients with BCR and should be further explored as a biomarker of therapeutic response.
PANRETINAL DEGENERATION ASSOCIATED WITH LONG-TERM HYDROXYCHLOROQUINE USE AND HETEROZYGOUS USH2A MUTATION
Authors: Katsman Diana , Sanfilippo Christian , Sarraf David
Published: September 2016

Purpose:

To report a case of bilateral panretinal degeneration in a patient with long-term hydroxychloroquine exposure and positive for a heterozygous mutation in the USH2A gene.

Methods:

Retrospective case report. Multimodal imaging including spectral-domain optical coherence tomography, fundus autofluorescence, and fluorescein angiography was performed and the results are presented. Electroretinography findings are also described.

Results:

The authors report a 39-year-old patient with a history of hydroxychloroquine therapy for 20 years (cumulative dose of 2,774 g). Multimodal retinal imaging demonstrated bilateral paracentral outer retinal atrophy with spectral-domain optical coherence tomography and characteristic of hydroxychloroquine toxicity. Full-field electroretinography showed bilateral panretinal depression of the rod and cone responses. Mutational analysis revealed that the patient was a carrier for an autosomal recessive mutation in the USH2A gene.

Conclusion:

We report a case of panretinal degeneration but with features characteristic of hydroxychloroquine retinopathy in a patient who was found to be a heterozygous carrier of the USH2A gene, a cause of recessive retinitis pigmentosa without hearing loss. Carrier status for a retinal degenerative mutation may have rendered this patient more susceptible to the retinotoxic effects of long-term hydroxychloroquine therapy.
New Small-Diameter Forceps for Thoracoscopic Surgery: Technical Adaptations and Initial Experiences
Authors: Tamura Masaya , Shimizu Yosuke
Published: September 2016

In this report, we describe the use of new small-diameter forceps (Endo Relief forceps) for port-reduced thoracoscopic surgery. Forceps were designed with end that were the same size and shape as conventional 5-mm forceps, except that the diameter of the shaft was decreased to 2.4 mm. Endo Relief forceps were used for thoracoscopic surgery in 18 patients. We retrospectively compared the frequency of grasping error between conventional small-diameter forceps and Endo Relief group. The mean surgical time was 57.5 minutes (range, 45–75 minutes). There were no complications, no recurrences of pneumothorax and lung cancer, and no deaths after surgery. There were no intraoperative complications and no need for a second surgery to open additional ports. The frequency of grasping error was significantly lower in the Endo Relief group compared to the conventional small-diameter forceps group (0.17 ± 0.23 vs 1.33 ± 0.22; P = 0.022). Our experience thus far indicates that this technique has cosmetic benefit and is as effective as the classic 3-port technique for experienced thoracoscopic surgeons. Endo Relief forceps has a safety comparing conventional small-diameter forceps.
Identifying Subgroups of Adult Superutilizers in an Urban Safety-Net System Using Latent Class Analysis
Authors: Rinehart Deborah J. , Oronce Carlos , Durfee Michael J. , Ranby Krista W. , Batal Holly A. , Hanratty Rebecca , Vogel Jody , Johnson Tracy L.
Published: September 2016

Background:

Patients with repeated hospitalizations represent a group with potentially avoidable utilization. Recent publications have begun to highlight the heterogeneity of this group. Latent class analysis provides a novel methodological approach to utilizing administrative data to identify clinically meaningful subgroups of patients to inform tailored intervention efforts.

Objective:

The objective of the study was to identify clinically distinct subgroups of adult superutilizers.

Research Design:

Retrospective cohort analysis.

Subjects:

Adult patients who had an admission at an urban safety-net hospital in 2014 and 2 or more admissions within the preceding 12 months.

Measures:

Patient-level medical, mental health (MH) and substance use diagnoses, social characteristics, demographics, utilization and charges were obtained from administrative data. Latent class analyses were used to determine the number and characteristics of latent subgroups that best represented these data.

Results:

In this cohort (N=1515), a 5-class model was preferred based on model fit indices, clinical interpretability and class size: class 1 (16%) characterized by alcohol use disorder and homelessness; class 2 (14%) characterized by medical conditions, MH/substance use disorders and homelessness; class 3 (25%) characterized primarily by medical conditions; class 4 (13%) characterized by more serious MH disorders, drug use disorder and homelessness; and class 5 (32%) characterized by medical conditions with some MH and substance use. Patient demographics, utilization, charges and mortality also varied by class.

Conclusions:

The overall cohort had high rates of multiple chronic medical conditions, MH, substance use disorders, and homelessness. However, the patterns of these conditions were different between subgroups, providing important information for tailoring interventions.
Is the Road to Mental Health Paved With Good Incentives? Estimating the Population Impact of Physician Incentives on Mental Health Care Using Linked Administrative Data
Authors: Puyat Joseph H. , Kazanjian Arminee , Wong Hubert , Goldner Elliot M.
Published: September 2016

Objectives:

The use of physician incentives to improve health care, in general, has been extensively studied but its value in mental health care has rarely been demonstrated. In this study the population-level impact of physician incentives on mental health care was estimated using indicators for receipt of counseling/psychotherapy (CP); antidepressant therapy (AT); minimally adequate counseling/psychotherapy; and minimally adequate antidepressant therapy. The incentives’ impacts on overall continuity of care and of mental health care were also examined.

Materials and Methods:

Monthly cohorts of individuals diagnosed with major depression were identified between January 2005 and December 2012 and their use of mental health services tracked for 12 months following initial diagnosis. Linked health administrative data were used to ascertain cases and measure health service use. Pre-post changes associated with the introduction of physician incentives were estimated using segmented regression analyses, after adjusting for seasonal variation.

Results:

Physician incentives reversed the downward and upward trends in CP and AT. Five years postintervention, the estimated impacts in percentage points for CP, AT, minimally adequate counseling/psychotherapy, and minimally adequate antidepressant therapy were +3.28 [95% confidence interval (CI), 2.05–4.52], −4.47 (95% CI, −6.06 to −2.87), +1.77 (95% CI, 0.94–2.59), and −2.24 (95% CI, −4.04 to −0.45). Postintervention, the downward trends in continuity of care failed to reverse, but were disrupted, netting estimated impacts of +7.53 (95% CI, 4.54–10.53) and +4.37 (95% CI, 2.64–6.09) for continuity of care and of mental health care.

Conclusions:

The impact of physician incentives on mental health care was modest at best. Other policy interventions are needed to close existing gaps in mental health care.
Psychosocial difficulties of individuals with multiple sclerosis: the PARADISE-24 questionnaire
Authors: Giovannetti Ambra M. , Schiavolin Silvia , Raggi Alberto , Quintas Rui , Cerniauskaite Milda , Confalonieri Paolo , Mantegazza Renato , Torri Clerici Valentina , Antozzi Carlo , Brenna Greta , Leonardi Matilde
Published: September 2016

The aim of this study is to identify the most relevant psychosocial difficulties (PSDs) experienced by persons with multiple sclerosis (PwMS); to evaluate the relation between an overall level of PSDs measured with the PARADISE-24 and other variables; to assess which factors may predict PARADISE-24 overall score. Adults PwMS were consecutively enrolled and completed a battery of eight self-reported instruments (i.e. SCQ, EUROHIS-QOL 8, BRS, BFI-10, JSPE, OSS-3, WHODAS-12, PARADISE-24). A clinical evaluation was performed for each patient and the Expanded Disability Status Scale (EDSS) score was determined by neurologists. A total of 80 PwMS, mean age 41.0, 65% women, 62% married, and 76.3% working, 86.3% relapsing-remitting MS, with an EDSS median score of 1.5, took part in the study. The mean disease duration was 7.7 years. The most frequently reported PSDs involved motor and emotional functioning. Free of charge access to medicines; health treatments and family, friends and health professionals’ assistance represented the most important facilitators. WHODAS-12 and EUROHIS-QOL 8 were excluded from regression because of their strong correlation with PARADISE-24. EDSS, BRS, OSS-3, and neuroticism were the main predictors of the PARADISE-24 score. Despite MS heterogeneity, a common pattern of PSDs can be observed among PwMS. The level of physical impairment and personal resilience were the main predictors of the overall level of PSDs in PwMS, with a lower but significant additional role played by social support and personality traits. Attention to PSDs and their predictors, using PARADISE-24, can help clinicians to plan tailored and personalized rehabilitation programs.
Caregiver Activation and Home Hospice Nurse Communication in Advanced Cancer Care
Authors: Dingley Catherine E. , Clayton Margaret , Lai Djin , Doyon Katherine , Reblin Maija , Ellington Lee
Published: September 2016

Background:

Activated patients have the skills, knowledge, and confidence to manage their care, resulting in positive outcomes such as lower hospital readmission and fewer adverse consequences due to poor communication with providers. Despite extensive evidence on patient activation, little is known about activation in the home hospice setting, when family caregivers assume more responsibility in care management.

Objective:

We examined caregiver and nurse communication behaviors associated with caregiver activation during home hospice visits of patients with advanced cancer using a prospective observational design.

Methods:

We adapted Street’s Activation Verbal Coding tool to caregiver communication and used qualitative thematic analysis to develop codes for nurse communications that preceded and followed each activation statement in 60 audio-recorded home hospice visits.

Results:

Caregiver communication that reflected activation included demonstrating knowledge regarding the patient/care, describing care strategies, expressing opinions regarding care, requesting explanations of care, expressing concern about the patient, and redirecting the conversation toward the patient. Nurses responded by providing education, reassessing the patient/care environment, validating communications, clarifying care issues, updating/revising care, and making recommendations for future care. Nurses prompted caregiver activation through focused care-specific questions, open-ended questions/statements, and personal questions.

Conclusions:

Few studies have investigated nurse/caregiver communication in home hospice, and, to our knowledge, no other studies focused on caregiver activation. The current study provides a foundation to develop a framework of caregiver activation through enhanced communication with nurses.

Implications for Practice:

Activated caregivers may facilitate patient-centered care through communication with nurses in home hospice, thus resulting in enhanced outcomes for patients with advanced cancer.
Trajectories of Symptom Clusters, Performance Status, and Quality of Life During Concurrent Chemoradiotherapy in Patients With High-Grade Brain Cancers
Authors: Kim Sang-hee , Byun Youngsoon
Published: September 2016

Background:

Symptom clusters must be identified in patients with high-grade brain cancers for effective symptom management during cancer-related therapy.

Objectives:

The aims of this study were to identify symptom clusters in patients with high-grade brain cancers and to determine the relationship of each cluster with the performance status and quality of life (QOL) during concurrent chemoradiotherapy (CCRT).

Methods:

Symptoms were assessed using the Memorial Symptom Assessment Scale, and the performance status was evaluated using the Karnofsky Performance Scale. Quality of life was assessed using the Functional Assessment of Cancer Therapy–General. This prospective longitudinal survey was conducted before CCRT and at 2 to 3 weeks and 4 to 6 weeks after the initiation of CCRT.

Results:

A total of 51 patients with newly diagnosed primary malignant brain cancer were included. Six symptom clusters were identified, and 2 symptom clusters were present at each time point (ie, “negative emotion” and “neurocognitive” clusters before CCRT, “negative emotion and decreased vitality” and “gastrointestinal and decreased sensory” clusters at 2–3 weeks, and “body image and decreased vitality” and “gastrointestinal” clusters at 4–6 weeks). The symptom clusters at each time point demonstrated a significant relationship with the performance status or QOL.

Conclusions:

Differences were observed in symptom clusters in patients with high-grade brain cancers during CCRT. In addition, the symptom clusters were correlated with the performance status and QOL of patients, and these effects could change during CCRT.

Implications for Practice:

The results of this study will provide suggestions for interventions to treat or prevent symptom clusters in patients with high-grade brain cancer during CCRT.
Proposal of a Provisional Classification of Sebaceous Carcinoma Based on Hormone Receptor Expression and HER2 Status
Authors: Na Hee Young , Choe Ji-Young , Shin Seon Ah , Choung Ho-kyung , Oh Sohee , Chung Jin-haeng , Park Mira , Kim Ji Eun
Published: September 2016

Despite recent progress in comprehensive genetic analysis, little is known about the molecular pathogenesis of sebaceous carcinoma. On the basis of the ontogenic proximity of sebaceous and mammary glands, we designed an intrinsic classification for sebaceous carcinoma adapted from that of breast cancer and evaluated its clinical significance. We investigated 42 cases of sebaceous carcinoma, including 32 ocular and 10 extraocular cases. Immunohistochemical analyses for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), HER2, Ki67, and CK5/6 and fluorescence in situ hybridization for the HER2 gene were performed. The immunohistochemistry for ER, PR, and AR showed positivity in 18 (42.9%), 11 (26.2%), and 34 (81.0%) cases, respectively. Expression of the HER2 protein was found in 10 (33.8%) cases, whereas extra copies were found in 3 (7.1%). According to our system, there were 16 (38.1%) cases of the luminal 1 subtype, 4 (9.5%) of the luminal 2 subtype, and 7 (16.7%) of the HER2 subtype, respectively. Fifteen cases (35.7%) belonged to the triple-negative group. In univariable analysis, loss of AR was significantly associated with shorter disease-free survival (P=0.020), whereas the expression of HER2 was associated with a better outcome with borderline significance (P=0.060). The luminal 2 subtype showed the best survival, and the all-negative subtype showed the worst (P=0.001). In multivariable analysis, negativity of PR or AR, low CK5/6, and female sex were independent poor prognostic factors (all P<0.05). This is the first study to categorize sebaceous carcinoma on the basis of the possible link between its molecular pathogenesis and future therapeutic applications.
Secretory Carcinoma of the Skin Harboring ETV6 Gene Fusions
Authors: Bishop Justin A. , Taube Janis M. , Su Albert , Binder Scott W. , Kazakov Dmitry V. , Michal Michal , Westra William H.
Published: September 2016

Mammary analogue secretory carcinoma is a low-grade salivary gland carcinoma that exhibits analogous features to secretory carcinoma of the breast including the presence of a t(12;15) translocation resulting in the ETV6-NTRK3 gene fusion. Rare cases of purported secretory carcinoma of the skin adnexa have been reported, but their relationship to true secretory carcinoma of the breast and salivary glands is unclear, as they generally do not harbor ETV6 rearrangements. Cases of cutaneous neoplasms with histologic features identical to secretory carcinoma of the breast and salivary glands were identified from the consultation files of 3 academic medical institutions. Immunohistochemistry was performed for S100 protein, mammaglobin and STAT5a. Break-apart fluorescence in situ hybridization was used evaluate for disruption of the ETV6 gene. Six cases of cutaneous secretory carcinoma were identified. The tumors arose in 4 women and 2 men, ranging from 24 to 71 years in age (mean, 47 y). The carcinomas presented in the skin of the axilla (n=4), ventral neck (n=1), and cheek (n=1). The tumors arose in the superficial dermis in association with adnexal structures. None of the patients had a prior or concurrent breast or salivary gland tumor. They were histologically characterized by well-circumscribed but unencapsulated proliferations of bland, eosinophilic cells arranged in microcysts and follicles with intraluminal secretions. Ectopic breast or salivary gland tissue was not identified. The cases were diffusely positive for S100 protein (6 of 6), mammaglobin (6 of 6), and STAT5a (5 of 5). All 6 cases harbored rearrangements of ETV6. All tumors were treated by simple excision alone. No recurrences or metastases developed in the 2 cases with follow-up. Secretory carcinoma of the skin represents a phenotypic, immunohistochemical, and genetic counterpart to secretory carcinoma of the breast and salivary glands. This tumor entity is less anatomically restricted than previously supposed.