bluuebunny/crossref_metadata_2025 huggingface dataset:
Consequences of Underestimating Impalement Bicycle Handlebar Injuries in Children
Authors: Ramos-Irizarry Carmen T. , Swain Shakeva , Troncoso-Munoz Samantha , Duncan Malvina
Published: December 2016

Impalement bicycle handlebar trauma injuries are rare; however, on initial assessment, they have the potential of being underestimated. We reviewed our prospective trauma database of 3,894 patients for all bicycle injuries from January 2010 to May 2015. Isolated pedal bike injuries were reported in 2.6% (N = 101) of the patients who were admitted to the trauma service. Fifteen patients suffered direct handlebar trauma. Patients were grouped into blunt trauma (n = 12) and impalement trauma (n = 3). We examined gender, age, injury severity score (ISS), Glasgow Coma Scale score, use of protective devices, need for surgical intervention, need for intensive care (ICU), and hospital length of stay. Mean age was 9.6 years. All children with penetrating injuries were males. Mean ISS was less than 9 in both groups. None of the children were wearing bicycle helmets. Three patients who sustained blunt injuries required ICU care due to associated injuries. All of the children with impalement injuries required several surgical interventions. These injuries included a traumatic direct inguinal hernia, a medial groin and thigh laceration with resultant femoral hernia, and a lateral deep thigh laceration. Impalement bicycle handlebar injuries must be thoroughly evaluated, with a similar importance given to blunt injuries. A high index of suspicion must be maintained when examining children with handlebar impalement injuries, as they are at risk for missed or underestimation of their injuries.
Impact of LVAD Implantation Site on Ventricular Blood Stagnation
Authors: Prisco Anthony R. , Aliseda Alberto , Beckman Jennifer A. , Mokadam Nahush A. , Mahr Claudius , Garcia Guilherme J. M.
Published: December 2016

Treatment of end-stage heart failure includes cardiac transplantation or ventricular assist device (VAD) therapy. Although increasingly prevalent, current VAD therapy has inherent complications, including thrombosis. Studies have demonstrated that VAD implantation alters intracardiac blood flow, creating areas of stagnation that predispose to thrombus formation. Two potential surgical configurations exist for VAD implantation: through the apical or diaphragmatic surfaces of the heart. We hypothesized that diaphragmatic implantation causes more stagnation than apical implantation. We also hypothesized that intermittent aortic valve (AV) opening reduces stagnation of blood inside the left ventricle (LV) when compared with a closed AV. To test these hypotheses, a human LV geometry was recreated in silico and a VAD inflow cannula was virtually implanted in each configuration. A computational indicator-dilution study was conducted where “virtually dyed blood” was washed out of the LV by injecting blood with no dye. Simulations demonstrated a substantial reduction in stagnation with intermittent AV opening. In addition, virtual dye was cleared slightly faster in the apical configuration. Simulations from our study demonstrate the clinical importance of VAD management to allow intermittent opening of the AV to prevent subvalvular stagnation, and also suggests that apical configuration might be more hemodynamically favorable.
Rehospitalization Patterns in Pediatric Outpatients with Continuous-Flow VADs
Authors: Hollander Seth A. , Chen Sharon , Murray Jenna M. , Lin Aileen , McBrearty Elizabeth , Almond Christopher S. , Rosenthal David N.
Published: December 2016

As continuous-flow ventricular assist devices (CF-VADs) are used increasingly in children and adolescents, more pediatric patients will be supported as outpatients. Herein we report the patterns of rehospitalization after CF-VAD implantation at a single center. We retrospectively reviewed the medical records of 19 consecutive patients who received CF-VADs between December 6, 2010 and November 5, 2016 and were discharged on device therapy. The frequency, duration, and indications for all hospitalizations between the time of implant hospitalization discharge and January 8, 2016 were analyzed. There were a total of 52 rehospitalization episodes in 16 (84%) patients over 5,101 (median 93, interquartile range [IQR] 38, 226) follow-up days. There were a median of two (IQR 1, 3) hospitalizations per patient. The median time to first hospitalization was 14 (IQR 7, 62) days. The most common admitting diagnoses were suspected infection 13 (28%) and suspected pump thrombosis in 8 (17%). Thirty-one (60%) hospitalizations included procedures, including seven (13%) requiring device-related surgery. Overall, 89% of postimplant discharge days were spent outside of the hospital. Children with CF-VADs can be discharged with acceptable readmission rates and significant time spent out of hospital. Most patients will be rehospitalized at least once between implant hospitalization and transplantation, often within 2 weeks of hospital discharge, with the most common indications for admission being suspected infection and suspected pump thrombosis. Device-related complications necessitating surgical intervention most frequently occur in destination therapy patients who are supported for longer periods of time.
Novel pathogenic variant in the HRAS gene with lethal outcome and a broad phenotypic spectrum among Polish patients with Costello syndrome
Authors: Pelc Magdalena , Ciara Elżbieta , Jezela-Stanek Aleksandra , Kugaudo Monika , Cieślikowska Agata , Jurkiewicz Dorota , Janeczko Magdalena , Chrzanowska Krystyna , Krajewska-Walasek Małgorzata , Skórka Agata
Published: December 2016

Costello syndrome (CS) is a rare congenital disorder from the group of RASopathies, characterized by a distinctive facial appearance, failure to thrive, cardiac and skin anomalies, intellectual disability, and a predisposition to neoplasia. CS is associated with germline mutations in the proto-oncogene HRAS, a small GTPase from the Ras family. In this study, a molecular and clinical analysis was carried out in eight Polish patients with the Costello phenotype. A molecular test showed two known heterozygous mutations in the first coding exon of the gene in seven patients: p.G12S (n=4) and p.G12A (n=3), and a novel pathogenic variant p.G60V in one child with an unusually severe, lethal course of the syndrome. In addition, a fatal course of CS was present in one patient with the p.G12A mutation and in another with p.G12S, there was a co-occurrence of Turner syndrome because of the distal Xp deletion. A severe clinical manifestation with a lethal outcome in an individual with p.G60V in HRAS and contrary observations of an attenuated phenotype in CS patients with other mutations at glycine-60 residue may suggest that the nature of the substituted amino acid plays a significant role in the clinical variability observed in some CS cases.
Outcomes With Fidaxomicin Therapy in Clostridium difficile Infection
Authors: Spiceland Clayton M. , Khanna Sahil , Pardi Darrell S.
Published: December 2016

Background and Goals:

Fidaxomicin is a new antibiotic used to treat Clostridium difficile infection (CDI). Given limited clinical experience with fidaxomicin, we assessed outcomes in a diverse cohort of patients with CDI treated with fidaxomicin.

Study:

All CDI cases treated with fidaxomicin at 3 referral centers over a 4-year period were included. Response was defined as resolution of diarrhea and recurrence was defined by recurrence of CDI within 8 weeks of the end of treatment.

Results:

Overall, 81 patients (median age 55.9 y; 53% female; 26% with inflammatory bowel disease) were included. Response occurred in 90%. Responders had fewer prior CDI episodes [median 1 (range, 0 to 8)] than nonresponders [median 2.5 (range, 1 to 8)], P=0.01. Response after a first CDI episode was 100%, 96% after 1 prior episode, and 82% after 2 or more, P=0.02. Recurrence occurred in 19%. Patients without recurrence had fewer prior episodes of CDI [median 1 (range, 0 to 6)] than patients who recurred [median 2 (range, 1 to 8)], P=0.005. Recurrence after a first episode was 0%, 23% after 1 prior episode, and 29% after 2 or more, P=0.005. All patients with inflammatory bowel disease responded either with improvement of symptoms or a negative C. difficile test; 19% recurred.

Conclusions:

All patients with a first CDI episode treated with fidaxomicin responded with no recurrences. Patients with prior CDI episodes were less likely to respond (especially with more than 1 prior episode) and more likely to recur, suggesting a greater clinical benefit of fidaxomicin earlier in the course of CDI.
Polycaprolactone Antimony Nanoparticles as Drug Delivery System for Leishmaniasis
Authors: Sousa-Batista Ariane de Jesus , Cerqueira-Coutinho Cristal , do Carmo Fagner Santos , Albernaz Marta de Souza , Santos-Oliveira Ralph
Published: December 2016

Background:

Leishmaniasis is a neglected disease endemic in tropical and subtropical areas, with an incidence about 1.6 million cases/year. The first-line treatment of this disease is pentavalent antimony, and the second-line are pentamidine and amphotericin B. All the treatments available cause severe side effects and often have difficulty in accessing parasites within infected cells.

Study Question:

This study aimed to determine if the use of nanoparticles loaded with meglumine antimoniate could reach and targeting infected organs with leishmaniasis, reducing the dosage used and promoting less adverse effects.

Study Design:

This study was performed comparing the meglumine nanoparticle in two experimental groups. The first one healthy mice and the second one inducted mice (leishmaniasis).

Measures and Outcomes:

The nanoparticles loaded with meglumine antimoniate (nanoantimony) were prepared by double-emulsion solvent evaporation method and showed a size of about 150–200 nm. BALB/c mice infected or not with Leishmania amazonensis (cutaneous leishmaniasis model) or Leishmania infantum (visceral leishmaniasis model) was used to access the biodistribution of nanoantimony and meglumine antimoniate labeled with technetium-99m.

Results:

The biodistribution profiles showed a preferential targeting of the nanoparticles to the liver, spleen, and lungs. Because these are the main organs infected, the nanoparticle may be used for this purpose. The results for cutaneous leishmaniasis showed a low uptake by the lesion (infected region).

Conclusions:

The results demonstrated the potential use of these nanoparticles to improve the efficacy of meglumine antimoniate in the treatment of visceral leishmaniasis, indicating their potential as an alternative therapeutic strategy for leishmaniasis infections.
Analysis of Immunogenetic Factors in Idiosyncratic Drug‐induced Liver Injury in the Pediatric Population
Authors: Ocete‐Hita Esther , Salmerón‐Fernández MaJ. , Urrutia‐Maldonado Emilia , Muñoz‐de‐Rueda Paloma , Salmerón‐Ruiz María , Martinez‐Padilla MaC. , Ruiz‐Extremera Angela
Published: December 2016

Objectives:

Idiosyncratic drug‐induced liver injury is a multifactorial complex disease, in which the toxic potential of the drug, together with genetic and acquired factors and deficiencies in adaptive processes, which limit the extent of damage, can determine susceptibility, and make individuals unique in their development of hepatotoxicity. The aim of the present study is to analyse the genetic factors (human leukocyte antigen [HLA], cytokine polymorphisms, and killer cell immunoglobulin‐like receptor [KIR] genotype) of children who experience an episode of drug‐induced liver injury.

Patients and Methods:

Prospective multicentre case‐control study. The subjects included in the study were 30 paediatric patients—infants and children ages between 0 and 15 years and who presented possible liver disease associated with the intake of medicines, herbal products, drugs, or toxins. As a control group, 62 subjects were selected.

Results:

Although HLAC0401 and HLADQB0603 may provide a hepatoprotective mechanism in the paediatric population, HLADQA0102 and HLA‐DR*12 are more commonly found in sick children and their presence may be related to liver damage. The KIR inhibitor KIR3DL1 was not present in any child in the control group.

Conclusions:

Polymorphisms that are low producers of interleukin‐10 occur more frequently in children who have experienced hepatotoxicity.
The Ethical Use of Mobile Health Technology in Clinical Psychiatry
Authors: Torous John , Roberts Laura Weiss
Published: December 2016

The rapid rise of mobile health technologies, such as smartphone apps and wearable sensors, presents psychiatry with new tools of potential value in caring for patients. Novel diagnostic and therapeutic applications of these technologies have been developed in private industry and utilized in mental health, although these methods do not yet constitute standard of care. In this article, we provide an ethical perspective on the practical use of this novel modality by psychiatrists. We propose that in the present context of limited scientific research and regulatory oversight, mobile technologies should serve to enhance the psychiatrist-patient relationship, rather than replace it, to minimize potential clinical and ethical harm to vulnerable patients. We analyze areas of possible ethical tension between clinical practice and the consumer-driven mobile industry, and develop a decision-tree model for implementing ethical safeguards in practice, focused on managing risk to the therapeutic relationship, informed consent, confidentiality, and mutual alignment of treatment goals and expectations.
Autoimmune Encephalitides: A Broadening Field of Treatable Conditions
Authors: Kalman Bernadette
Published: December 2016

Background:

Neurology has been continuously transforming by the refinement of molecular diagnostics and the development of disease-modifying treatments. The discovery of new antibody markers has elucidated the pathogenesis, provided the means of diagnostics, and offered cure or treatment for several immune-mediated neurological and neuropsychiatric disorders. The identification of pathogenic and marker autoantibodies has also facilitated defining the associated phenotypic spectra and the overlap among the phenotypes linked to individual immune markers.

Review Summary:

This survey presents the list of currently known autoimmune encephalitis entities along with the associated marker autoantibodies, highlights the phenotypic and immune pathogenic relationships, calls attention to the recently described rare syndromes, discusses the biological significance of the autoantibodies and targeted molecules, points out the potential postinfectious origin of immune pathogenesis in several of the disorders, and directs the readers to the latest diagnostic guidelines as well as to the generally used treatment approaches.

Conclusions and Future Directions:

Owing to the successful and usually combined use of various methods to detect serum and cerebrospinal fluid autoantibodies on rodent brain sections, in primary neuronal cell culture, in immune precipitation, and cell-based assays, or in other antigen-specific immune assays (Western blot, enzyme-linked immunosorbent assay, and radioimmune assay), the subgroup of antibody marker-negative autoimmune encephalopathy syndromes is contracting, whereas the numbers of entities within the overall group are expanding. Recognition of the correct diagnosis is becoming increasingly rewarding not only for neurologists, but also for pediatric neurologists and psychiatrists.
Fatal Morvan Syndrome Associated With Myasthenia Gravis
Authors: Nagappa Madhu , Mahadevan Anita , Sinha Sanjib , Bindu Parayil S. , Mathuranath Pavagada S. , Bineesh Cheminikara , Bharath Rose D. , Taly Arun B.
Published: December 2016

Introduction:

Morvan syndrome is a rare and complex autoimmune disorder affecting multiple sites of neuraxis.

Case Report:

We present fulminant Morvan syndrome, developing on a background of chronic myasthenia gravis. A 54-year-old gentleman presented with fluctuating ophthalmoplegia and proximal muscles weakness of 7 years duration that remitted with pyridostigmine and prednisolone. He developed insomnia of 2 months duration, worsening of myasthenic symptoms and respiratory distress, dysautonomia, encephalopathy, and peripheral nerve hyperexcitability. Antibodies against contactin-associated protein (CASPR) 2 were detected in serum. Computed tomography of thorax showed a thymic mass. He received intravenous methyl prednisolone and plasmapheresis. Antibodies against CASPR and thymic lesion reduced with immunotherapy. However, he developed persistent hypotension and expired after 11 weeks of hospital stay.

Conclusions:

Clinical clues for diagnosis of Morvan syndrome and therapeutic changes faced by the treating team are highlighted in this report. Increased awareness and prompt testing for CASPR2 antibody is warranted so that early immunotherapy can be initiated.
Accommodation and Phoria in Children Wearing Multifocal Contact Lenses
Authors: Gong Celia R. , Troilo David , Richdale Kathryn
Published: December 2016

Purpose

To determine the effect of multifocal contact lenses on accommodation and phoria in children.

Methods

This was a prospective, non-dispensing, randomized, crossover, single-visit study. Myopic children with normal accommodation and binocularity and no history of myopia control treatment were enrolled and fitted with CooperVision Biofinity single vision (SV) and multifocal (MF, +2.50D center distance add) contact lenses. Accommodative responses (photorefraction) and phorias (modified Thorington) were measured at four distances (>3 m, 100 cm, 40 cm, 25 cm). Secondary measures included high- and low-contrast logMAR acuity, accommodative amplitude, and facility. Differences between contact lens designs were analyzed using repeated measures regression and paired t-tests.

Results

A total of 16 subjects, aged 10 to 15 years, completed the study. There was a small decrease in high (SV: −0.08, MF: +0.01) and low illumination (SV: −0.03, MF: +0.08) (both P < .01) visual acuity, and contrast sensitivity (SV: 2.0, MF: 1.9 log units, P = .015) with multifocals. Subjects were more exophoric at 40 cm (SV: −0.41, MF: −2.06 Δ) and 25 cm (SV: −0.83, MF: −4.30 Δ) (both P < .01). With multifocals, subjects had decreased accommodative responses at distance (SV: −0.04; MF: −0.37D, P = .02), 100 cm (SV: +0.37; MF: −0.35D, P < .01), 40 cm (SV: +1.82; MF: +0.62D, P < .01), and 25 cm (SV: +3.38; MF: +1.75D, P < .01). There were no significant differences in accommodative amplitude (P = .66) or facility (P = .54).

Conclusions

Children wearing multifocal contact lenses exhibited reduced accommodative responses and more exophoria at increasingly higher accommodative demands than with single vision contact lenses. This suggests that children may be relaxing their accommodation and using the positive addition or increased depth of focus from added spherical aberration of the multifocals. Further studies are needed to evaluate other lens designs, different amounts of positive addition and aberrations, and long-term adaptation to lenses.
Penicillin-Induced Fulminant Myocarditis
Authors: Ben Khelil Mehdi , Chkirbene Youssef , Mlika Mona , Haouet Slim , Hamdoun Moncef
Published: December 2016

Drug-induced eosinophilic myocarditis is uncommon with few cases reported in the literature. It is a rare but potentially life-threatening disease.

We report the case of an 11-year-old girl without medical history who developed an acute malaise and chills, followed by severe shortness of breath and a cardiopulmonary arrest 1 hour after an intramuscular injection of penicillin.

At autopsy, we observed in the external examination nonspecific asphyxia signs, an injection mark, and the absence of traumatic signs. The organs examination showed a heart with a normal shape and a transmural, diffuse, tannish discoloration of the myocardium. The lungs were severely congested with a diffuse edema. Histological examination of the ventricular walls and septum revealed suggestive signs of eosinophilic myocarditis. Immunohistochemical analysis for the phenotypic characterization of the inflammatory cells revealed the positivity of the CD3 antibody without any stain for CD20.

The diagnosis of fulminant myocarditis with an eosinophilic infiltrate was established as the cause of death. The manner of death was stated as natural.
Precision Medicine Starts With Preanalytics: Real-Time Assessment of Tissue Fixation Quality by Ultrasound Time-of-Flight Analysis
Authors: Lerch Melissa L. , Bauer Daniel R. , Chafin David , Theiss Abbey , Otter Michael , Baird Geoffrey S.
Published: December 2016

Personalized medicine promises diagnosis and treatment of disease at the individual level and relies heavily on clinical specimen integrity and diagnostic assay quality. Preanalytics, the collection and handling steps of a clinical specimen before immunohistochemistry or other clinical assay, are critically important to enable the correct diagnosis of disease. However, the effects of preanalytics are often overlooked due to a lack of standardization and limited assessment tools to quantify their variation. Here, we report a novel real-time ultrasound time-of-flight instrument that is capable of monitoring and imaging the critical step in formalin fixation, diffusion of the fixative into tissue, which provides a quantifiable quality metric for tissue fixation in the clinical laboratory ensuring consistent downstream molecular assay results. We analyzed hundreds of tissue specimens from 34 distinct human tissue types and 12 clinically relevant diseased tissues for diffusion and fixation metrics. Our measurements can be converted into tissue diffusivity constants that correlate with the apparent diffusion constant calculated using magnetic resonance imaging (R
2=0.83), despite the differences in the approaches, indicating that our approach is biophysically plausible. Using data collected from time-of-flight analysis of many tissues, we have therefore developed a novel rapid fixation program that could ensure high-quality downstream assay results for a broad range of human tissue types.
Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene
Authors: Williamson Sean R. , Grignon David J. , Cheng Liang , Favazza Laura , Gondim Dibson D. , Carskadon Shannon , Gupta Nilesh S. , Chitale Dhananjay A. , Kalyana-Sundaram Shanker , Palanisamy Nallasivam
Published: December 2016

Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients’ ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K. Novel TFEB fusions were reported by TCGA in 2; however, due to a small composition of fusion transcripts compared with full-length transcripts (0.5/174 and 3.3/132 FPKM), we hypothesize that these represent secondary fusions due to amplification. Five specimens (4 TCGA, 1 fluorescence in situ hybridization) had concurrent chromosome 3p copy number loss or VHL deletion. However, these did not resemble clear cell RCC, had negative carbonic anhydrase IX labeling, lacked VHL mutation, and had papillary or unclassified histology (2/4 had gain of chromosome 7 or 17). One tumor each had somatic FH mutation and SMARCB1 mutation. Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology. The combined constellation of features does not fit cleanly into an existing tumor category (unclassified), most closely resembling papillary or translocation RCC. The tendency for high tumor stage, varied tubulopapillary morphology, and a subset with melanocytic marker positivity suggests the possibility of a unique tumor type, despite some variation in appearance and genetics.
Hobnail Variant of Papillary Thyroid Carcinoma
Authors: Cameselle-Teijeiro José M. , Rodríguez-Pérez Irene , Celestino Ricardo , Eloy Catarina , Piso-Neira Magalí , Abdulkader-Nallib Ihab , Soares Paula , Sobrinho-Simões Manuel
Published: December 2016

The hobnail variant (HV) of papillary thyroid carcinoma (PTC) is an unusual entity recently proposed as an aggressive variant of PTC. We describe the pathologic and molecular features of 2 cases of HV of PTC. Both tumors presented in stage III (pT3 pN1a M0). The first case was diagnosed in a 62-year-old man, whereas the second was in a 53-year-old woman. Both patients were treated with total thyroidectomy and radioactive iodine. The primary tumors showed a hobnail/micropapillary pattern in ≥50% of the neoplasm, and positivity for TTF-1, TTF-2, thyroglobulin (TG), cyclin D1, and p53. The Ki-67 index was 4.6% and 5%, respectively. In case 1, the tumor disclosed BRAFV600E and TERT C228T (124:G>A) promoter gene mutation, negativity for NRAS, HRAS, and KRAS mutations, and negativity for RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements. After 11 years the patient died with cervical lymph node, bone, and liver metastases. In the liver metastasis, the tumor displayed columnar cell PTC areas (positive for TTF-1, TG, and BRAFV600E) merging with undifferentiated carcinoma (UC) areas (positive for TTF-1 and BRAFV600E; negative for TG). In case 2, the patient died 6 years after treatment with local recurrence and disseminated metastases to the lung, pleura, bone, and liver. The tumor recurrence showed a UC component (positive for cyclin D1 and p53; negative for TTF-1 and TG) with a residual HV of PTC (positive for cyclin D1, p53, TTF-1, and TG). No BRAF, TERT, NRAS, HRAS, nor KRAS mutations were detected in the primary tumor or recurrence in case 2. Our findings suggest that p53-positive HV is a very aggressive form of PTC prone to progression to UC.
Alveolar Soft Part Sarcoma of the Female Genital Tract
Authors: Schoolmeester J. Kenneth , Carlson Joseph , Keeney Gary L. , Fritchie Karen J. , Oliva Esther , Young Robert H. , Nucci Marisa R.
Published: December 2016

Alveolar soft part sarcoma (ASPS) is a morphologically distinctive neoplasm of unknown differentiation that bears a characteristic gene fusion involving ASPSCR1 and TFE3. ASPS can occur in the female genital tract, but is rare. Eleven cases with an initial diagnosis of ASPS at female genital tract sites were evaluated for their morphologic features and immunoprofile using a panel of antibodies (TFE3, HMB45, melan-A, smooth muscle actin, desmin, and h-Caldesmon). In addition, the presence of TFE3 rearrangement and subsequent ASPSCR1-TFE3 fusion were determined by fluorescence in situ hybridization. Ten tumors retained their classification as ASPS based on their morphologic appearance, immunohistochemical profile, and demonstration of ASPSCR1-TFE3 fusion. The remaining case was reclassified as conventional-type PEComa due to its pattern of HMB45, melan-A, and desmin positivity as well as absence of TFE3 rearrangement. Sites of the 10 ASPS were uterine corpus (3), cervix (2), uterus not further specified (2), vagina (2), and vulva (1). The age of the patients ranged from 15 to 68 years (mean 34 y, median 32 y). The tumors demonstrated a spectrum of morphologic features, but all had a consistent immunophenotype of strong TFE3 nuclear expression and lack of muscle (smooth muscle actin, desmin, h-Caldesmon) and melanocytic (melan-A, HMB45) markers, except focal positivity for HMB45 in 1. Follow-up was available for 4 patients ranging from 1 to 35 months (mean 15 mo, median 25 mo) and they were alive and had no evidence of recurrence or metastasis at last follow-up. Distinguishing ASPS from its morphologic mimics, particularly PEComa, is important due to increasingly efficacious targeted agents such as MET-selective and VEGF signaling inhibitors in the former and mTOR inhibition therapy in the latter.
The Importance of Patient Satisfaction: A Blessing, a Curse, or Simply Irrelevant?
Authors: Cohen Justin B. , Myckatyn Terence M. , Brandt Keith
Published: December 2016

New regulations require that physician performance must be evaluated and graded in both objective and subjective ways. This represents a novel factor in American health care delivery driven by the reality that the United States spends more than any other nation on health care yet still lags behind in key outcome measures. Patient satisfaction has been established as a core component of physician rankings and reimbursement. In fact, it already has acted as both a powerful motivator and stressor. Patient feedback has driven hospital administrators’ agendas to improve facilities and provide relative luxuries to inpatients, and individual providers have been tempted to ignore sound medical judgment by relenting to patient requests to increase their satisfaction scores. Unfortunately, there is little high-level evidence to support that patient satisfaction will improve medical outcomes, and there are plenty of contradictory data in smaller studies. Part of the difficulty of these studies may lie in the diversity of patient expectations, which are dependent on the disease process and the inherently subjective and labile nature of people’s responses. Reliable tools are needed that will take into account what constitutes a superior quality of patient care in a more systematic, meaningful, and validated way.
Establishment of an Acquired Lymphedema Model in the Mouse Hindlimb: Technical Refinement and Molecular Characteristics
Authors: Iwasaki Daisuke , Yamamoto Yuhei , Murao Naoki , Oyama Akihiko , Funayama Emi , Furukawa Hiroshi
Published: December 2016

Background:

The pathophysiology of secondary lymphedema remains poorly understood. This study aimed to establish a consistent mouse hindlimb lymphedema model for further investigation of the mechanism and treatment of lymphedema.

Methods:

The authors developed a novel postsurgical lymphedema model in the mouse hindlimb by modifying previously described methods. Lymphedema in the hindlimb was created by removing both the inguinal and popliteal lymph nodes together with the surrounding fat pads, followed by silicone splint placement in the inguinal region. Using this modified mouse model, the authors analyzed lymphatic function, histologic changes, and the expression of lymphangiogenic factors including vascular endothelial growth factor C at various time points.

Results:

The splinted lymphedema model showed a significant increase of edema formation in the hindlimb compared with the sham surgery control animals. Indocyanine green lymphography revealed lymphatic drainage impairment shown by dermal backflow and rerouting of lymph flow in the lymphedema model. Histopathologic and immunohistochemical examinations showed a significant increase of skin thickness and abnormally dilated lymphatics in the lymphedema model. The expression of lymphangiogenic factors in lymphedematous tissues of the splinted lymphedema model was significantly increased compared with controls, depending on the degree of lymphedema.

Conclusions:

This splinted lymphedema model closely simulates the volume response, histopathology, and lymphography characteristics of human acquired lymphedema. Given these similarities to human lymphedema, this refinement of a mouse hindlimb model of acquired lymphedema represents a promising platform for the study of lymphatic vascular insufficiency and for the evaluation of new therapeutic modalities.
Anatomy of the Facial Danger Zones: Maximizing Safety during Soft-Tissue Filler Injections
Authors: Scheuer Jack F. , Sieber David A. , Pezeshk Ronnie A. , Campbell Carey F. , Gassman Andrew A. , Rohrich Rod J.
Published: December 2016

With limited downtime and immediate results, facial filler injections are becoming an ever more popular alternative to surgical rejuvenation of the face. The results, and the complications, can be impressive. To maximize safety during injections, the authors have outlined general injection principles followed by pertinent anatomy within six different facial danger zones. Bearing in mind the depth and the location of the vasculature within each zone, practitioners can tailor their injection techniques to prevent vessel injury and avoid cannulation.
The Impact of Subjective Well-being on Mortality: A Meta-Analysis of Longitudinal Studies in the General Population
Authors: Martín-María Natalia , Miret Marta , Caballero Francisco Félix , Rico-Uribe Laura Alejandra , Steptoe Andrew , Chatterji Somnath , Ayuso-Mateos José Luis
Published: December 2016

Objective

The aims of the study were to assess whether subjective well-being is a protective factor for mortality in the general population and to analyze the differential impact of evaluative, experienced, and eudaimonic well-being.

Methods

Systematic review of articles in the PsycINFO, Web of Science, and PubMed databases. Data on the studies' characteristics, quality, and the effects of variables were extracted. A meta-analysis was conducted on the studies included in the systematic review.

Results

A total of 62 articles that investigated mortality in general populations, involving 1,259,949 participants, were found, and added to those considered in a previously published review (n = 14). The meta-analysis showed that subjective well-being was a protective factor for mortality (pooled hazard ratio = 0.920; 95% confidence interval = 0.905–0.934). Although the impact of subjective well-being on survival was significant in both men and women, it was slightly more protective in men. The three aspects of subjective well-being were significant protective factors for mortality. The high level of heterogeneity and the evidences of publication bias may reduce the generalizability of these findings.

Conclusions

Our results suggest that subjective well-being is associated with a decreased risk of mortality. Longitudinal studies examining changing levels of well-being and their relationship to longevity would be required to establish a cause–effect relationship. Establishing such a causal relationship would strengthen the case for policy interventions to improve the population subjective well-being to produce longevity gains combined with optimizing quality of life.
The Detection, Analysis, and Significance of Physician Clustering in Medical Malpractice Lawsuit Payouts
Authors: Oshel Robert E. , Levitt Philip
Published: December 2016

Objectives

There is evidence that most adverse events result from individual errors and that most malpractice suits with payouts reflect both patient injury and error. Hypothesis: There are outlier physicians with regard to the frequency and total amount of malpractice payouts.

Methods

Using the public use file of the National Practitioner Data Bank (NPDB), we sought the percentage of physicians who lay above several cutoff points with regard to total amounts of payments and number of payments. We looked at the frequency with which outliers were likely to have additional paid claims and to be disciplined by their hospitals and state boards.

Results

Approximately 1.8% of physicians were responsible for half of the $83,368,588,200 reported to the NPDB over 25 years. Within that group, 12.6% had an adverse licensure action reported to the NPDB, and 6.3% had a clinical privileges action reported. Physicians who were in the high dollar payout category and had one malpractice claim payout had a 74.5% chance of another payout, more than twice the rate for all physicians who had a single payout (chi-square, P < 0.0001). The likelihood that that physician would have additional payments increased as the number of previous payments increased. Total dollar payouts per physician better predicted future payouts than numbers of payouts. (For 1, 2, and 3 payouts, the P value was less than 0.0001 for each category.) Limitations: Neither a prospective nor a randomized study was feasible. Sorting by specialty was not done. Malpractice cases are an indirect measure of adverse events.

Conclusions

There is a clustering of payments in medical malpractice cases among a small group of physicians. These findings point up the need to oppose the negative impact of such outlier physicians on the safety of patients.
Antibiotic dosing for multidrug-resistant pathogen pneumonia
Authors: Abdul-Aziz Mohd. H. , Lipman Jeffrey , Roberts Jason A.
Published: December 2016

Purpose of review

Nosocomial pneumonia caused by multidrug-resistant pathogens is increasing in the ICU, and these infections are negatively associated with patient outcomes. Optimization of antibiotic dosing has been suggested as a key intervention to improve clinical outcomes in patients with nosocomial pneumonia. This review describes the recent pharmacokinetic/pharmacodynamic data relevant to antibiotic dosing for nosocomial pneumonia caused by multidrug-resistant pathogens.

Recent findings

Optimal antibiotic treatment is challenging in critically ill patients with nosocomial pneumonia; most dosing guidelines do not consider the altered physiology and illness severity associated with severe lung infections. Antibiotic dosing can be guided by plasma drug concentrations, which do not reflect the concentrations at the site of infection. The application of aggressive dosing regimens, in accordance to the antibiotic's pharmacokinetic/pharmacodynamic characteristics, may be required to ensure rapid and effective drug exposure in infected lung tissues.

Conventional antibiotic dosing increases the likelihood of therapeutic failure in critically ill patients with nosocomial pneumonia. Alternative dosing strategies, which exploit the pharmacokinetic/pharmacodynamic properties of an antibiotic, should be strongly considered to ensure optimal antibiotic exposure and better therapeutic outcomes in these patients.
Does Appearance Matter? Current Issues and Formulation of a Research Agenda for Moulage in Simulation
Authors: Stokes-Parish Jessica B. , Duvivier Robbert , Jolly Brian
Published: December 2016

Summary Statement

The use of moulage is assumed to add realism and authentic context in simulation. Despite the expense required to utilize moulage effectively, there is little exploration in the literature as to both its necessity and its accuracy of portrayal. We explore engagement, authenticity, and realism theories in the context of moulage and highlight the need for more evidence on moulage in simulation-based education, including suggestions for future research. In particular, we urge the simulation community to move beyond descriptive papers to investigate moulage in terms of justification and clarification.
The Effects of High-Concentration Oxygen on Inflammatory Markers in Laparoscopic Cholecystectomy: A Randomized Controlled Trial
Authors: Schietroma Mario , Colozzi Sara , Pessia Beatrice , Carlei Francesco , Amicucci Gianfranco
Published: December 2016

Background:

This study assessed effect of administration of high-concentration supplemental perioperative oxygen on systemic inflammatory and immune response in patients undergoing elective laparoscopic cholecystectomy.

Materials and Methods:

One hundred seventy-seven patients were assigned randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of 30% (n=88) or 80% (n=89). White blood cells, peripheral lymphocytes subpopulation, human leukocyte antigen-DR, neutrophil elastase, interleukin (IL)-1 and IL-6, and C-reactive protein were investigated.

Results:

Significantly higher concentration of neutrophil elastase, IL-1, IL-6 and C-reactive protein was detected postoperatively in the 30% FiO2 group patients in comparison with the 80% FiO2 group (P<0.05). Statistically significant change in human leukocyte antigen-DR expression was recorded postoperatively at 24 hours, as a reduction of this antigen expressed on monocyte surface in patients from 30% FiO2 group.

Conclusions:

This study demonstrated that high-concentration (80%) supplemental perioperative oxygen can lead to a reduction in postoperative inflammatory response and avoid postoperative immunosuppression.
Application of Operational Tolerance Signatures Are Limited by Variability and Type of Immunosuppression in Renal Transplant Recipients: A Cross-Sectional Study
Authors: Bottomley Matthew J. , Chen Mian , Fuggle Sue , Harden Paul N. , Wood Kathryn J.
Published: December 2016

Background

Renal transplant recipients (RTR) frequently develop complications relating to chronic immunosuppression. Identifying RTR who could safely reduce immunosuppression is therefore highly desirable. We hypothesized that “signatures” described in RTR who have stopped immunosuppression but maintained stable graft function (“operational tolerance”) may enable identification of immunosuppressed RTR who are candidates for immunosuppression minimization. However, the effect of immunosuppression itself on these signatures and circulating B-cell populations is currently unknown.

Methods

We undertook a cross-sectional study of 117 RTR to assess the effect of immunosuppression upon circulating B cell populations, humoral alloresponse and 2 previously published “signatures” of operational tolerance.

Results

Immunosuppression associated with alterations in both published “signatures.” Azathioprine associated with a decrease in transitional and naive B-cell numbers and calcineurin inhibition associated with an increase in the number of circulating plasmablasts. However, only azathioprine use associated with the presence of donor-specific anti-HLA IgG antibodies. Calcineurin inhibition associated with an increase in total serum IgM but not IgG. Data were corrected for age, time since last transplant, and other immunosuppression.

Conclusions

Current signatures of operational tolerance may be significantly affected by immunosuppressive regimen, which may hinder use in their current form in clinical practice. Calcineurin inhibition may prevent the development of long-lasting humoral alloresponses, whereas azathioprine therapy may be associated with donor specific antibody development.
Analysis of copy number variants on chromosome 21 in Down syndrome-associated congenital heart defects
Authors: Rambo-Martin Benjamin L. , Mulle Jennifer G. , Cutler David J. , Bean Lora J.H. , Rosser Tracie C. , Dooley Kenneth J. , Cua Clifford , Capone George , Maslen Cheryl L. , Reeves Roger H. , Sherman Stephanie L. , Zwick Michael E.
Published: December 2016

One in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2,000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: 1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and 2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 198 case individuals with DS+AVSD and 211 control individuals with DS and a normal heart using a custom microarray with dense probes tiled on chromosome 21 for array CGH. We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. Pathway analyses indicated copy number perturbations of genes involved in protein heterotrimerization and histone methylating proteins. Finally, we showed that previously DS+AVSD-associated common CNVs on chromosome 21 are likely false positives. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population.
Assembly of photoactive Orange Carotenoid Protein from its domains unravels a carotenoid shuttle mechanism
Authors: Moldenhauer Marcus , Sluchanko Nikolai N. , Buhrke David , Zlenko Dmitry V. , Tavraz Neslihan N. , Schmitt Franz-Josef , Hildebrandt Peter , Maksimov Eugene G. , Friedrich Thomas
Published: December 2016

The Orange Carotenoid Protein (OCP) is indispensable for cyanobacterial photoprotection by quenching phycobilisome fluorescence upon photoconversion from the orange OCPOto the red OCPRform. Cyanobacterial genomes frequently harbor, besides genes for Orange Carotenoid Proteins (OCPs), several genes encoding homologs of OCP’s N- or C-terminal domains (NTD, CTD). Unlike the well-studied NTD homologs, called Red Carotenoid Proteins (RCPs), the role of CTD homologs remains elusive. We show how OCP can be reassembled from its functional domains. Expression ofSynechocystisOCP-CTD in carotenoid-producingEscherichia coliyielded violet-colored proteins, which, upon mixing with the RCP-apoprotein, produced an orange-like photoswitchable form that further photoconverted into a species spectroscopically indistinguishable from RCP, thus demonstrating a unique carotenoid shuttle mechanism. The CTD itself is a novel, dimeric carotenoid-binding protein, which effectively quenches singlet oxygen and interacts with the Fluorescence Recovery Protein, assigning physiological roles to CTD homologs and explaining the evolutionary process of OCP formation.

One Sentence Summary

The C-domain of cyanobacterial OCP dimerizes, binds a carotenoid, and delivers it to the N-domain forming photoactive OCP.
Ecological speciation within thePhytophthoragenus
Authors: Mideros M. F. , Turissini D. A. , Guayazán N. , Danies G. , Cárdenas M. , Myers K. , Tabima J. , Goss E. M. , Bernal A. , Lagos L. E. , Grajales A. , Gonzalez L. N. , Cooke D. E. L. , Fry W. E. , Grünwald N. , Matute D. R. , Restrepo S.
Published: December 2016

Over the past few years, symptoms akin to late blight disease have been reported on a variety of crop plants in South America. Despite the economic importance of these crops, the causal agents of the diseases belonging to the genusPhytophthorahave not been completely characterized. In this study, we used an integrative approach that leveraged morphological, ecological, and genetic approaches to explore cryptic speciation withinP. infestans sensu lato. We described a newPhytophthoraspecies collected in Colombia from tree tomato (Solanum betaceum), a semi-domesticated fruit. All morphological traits and population genetic analyses, using microsatellite data and a reduced representation of single nucleotide polymorphism (SNP) data, support the description of the new species,Phytophthora betaceisp. nov. We have demonstrated that ecological differences are important in the persistence ofP. infestansandP. betaceias genetically isolated units across an overlapping area in the northern Andes.
HILAQ: A Novel Strategy for Newly Synthesized Protein Quantification
Authors: Ma Yuanhui , McClatchy Daniel B. , Barkallah Salim , Wood William W. , Yates John R.
Published: December 2016

Here we describe a new strategy, HILAQ (HeavyIsotopeLabeledAzidohomoalanineQuantification), to rapidly quantify the molecular vulnerability profile to oxytosis. HILAQ quantified more than 1,900NewlySynthesizedProteins (NSP) after 1h pulse labeling in HEK293T cell line. Compared with the previous published QuaNCAT protocol, the HILAQ strategy simplifies newly synthesized proteome analysis and achieves higher sensitivity.