bluuebunny/crossref_metadata_2025 huggingface dataset:
ASSOCIATION BETWEEN THE VITREOMACULAR INTERFACE AND OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS IN WET AGE-RELATED MACULAR DEGENERATION
Authors: Ashraf Mohammed , Souka Ahmed , Adelman Ron A.
Published: December 2016

Purpose:

To study the effect of the vitreomacular interface on various wet age-related macular degeneration (AMD) characteristics including the size and type of choroidal neovascularization (CNV), choroidal thickness, and activity of the CNV.

Methods:

This was a retrospective observational cross-sectional study. The study included 43 patients (51 eyes) with treatment-naive age-related macular degeneration. Twenty-six patients with wet AMD in one eye and dry AMD in the other eye were included in a paired-eye analysis. Patients underwent optical coherence tomography examination using Heidelberg Spectralis (spectral domain optical coherence tomography) at presentation to determine the type of CNV and the vitreomacular status. In addition, various parameters were measured including the choroidal thickness and horizontal width and vertical height measurements of the CNV.

Results:

There was no correlation between the height, width, activity or type of the CNV, and the presence or absence of vitreomacular adhesion. The mean choroidal thickness (using enhanced depth imaging) in cases with vitreomacular adhesion was 272.57 μm compared with 197.32 μm in cases with no vitreomacular adhesion, a statistically significant difference (P = 0.003). In the paired-eye study (21 patients), there was no significant difference between the eyes with wet AMD and dry AMD with regard to vitreomacular status or the choroidal thickness. In a subgroup analysis, patients with Type 1 CNV had a significantly higher percentage of vitreomacular adhesion compared with the other eye with dry AMD (P = 0.034).

Conclusion:

In conclusion, the vitreomacular interface does seem to be associated with an increased choroidal thickness in cases of wet AMD. Furthermore, the association between the vitreomacular interface and wet AMD is more significant for Type 1 CNV.
TWENTY-FIVE-GAUGE CANNULA–ASSISTED FINE-NEEDLE ASPIRATION BIOPSY OF CHOROIDAL MELANOMA
Authors: Singh Arun D. , Aziz Hassan A. , Pelayes David , Biscotti Charles V.
Published: December 2016

Purpose:

To report cytopathological observations on the cells retrieved from the 25-G cannula used during prognostic transvitreal fine-needle aspiration biopsy of choroidal melanoma.

Methods:

Transvitreal fine-needle aspiration biopsy of choroidal melanoma was performed through a 25-G valved cannula. Twenty samples from 20 consecutive patients were obtained. Most tumors were treated with plaque radiation therapy (16/20, 80%) following standard clinical guidelines. Four enucleated globes (4/20, 20%) were subjected to a similar transvitreal biopsy before enucleation.

Results:

Cytopathological analysis of the cells retrieved from the cannula revealed the absence of any cells in 4 of 20 samples (20%). In the remaining 16 samples, definite melanoma cells and atypical cells (probable melanoma cells) were observed in 2 samples each (total 4, 25%). Histiocytes (4/16, 25%) and lymphocytes (1/16, 6%) were also observed. Thirteen samples (13/16, 81%) contained conjunctival epithelial epithelium. Prognostication could be performed on all fine-needle aspiration biopsy samples (20, 100%).

Conclusion:

Use of a 25-G valved cannula offers potential advantages by isolating the needle tract and by allowing retrieval of the contaminating cells without affecting the prognostic yield of the fine-needle aspiration biopsy sample.
UNILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION
Authors: Spaide Richard F.
Published: December 2016

Purpose:

To report a unilateral case of what is named bilateral diffuse uveal melanocytic proliferation and consider the consequences of this finding.

Methods:

The ocular findings were investigated with multimodal imaging to include color fundus photography, fluorescein angiography, autofluorescence imaging, and enhanced depth imaging optical coherence tomography.

Results:

A 66-year-old woman had a history of breast cancer 23 years previously that was treated and the patient was free of disease since. She developed a recent decrease in visual acuity in her left eye prompting referral. She was seen to have an alteration in the pigmentation of the posterior pole of the left eye with dispersed red placoid spots. Autofluorescence imaging showed nummular areas of absent autofluorescence signal, which corresponded to areas of hyperfluorescence during fluorescein angiography. The placoid spots were hyperautofluorescent and hypofluorescent in autofluorescence and fluorescein angiography, respectively. She had diffuse thickening and infiltration of the choroid in the left eye. Because of the ocular findings, the patient underwent a systemic evaluation and was found to have widely metastatic disease with an unknown primary cancer. No progression of disease was seen in the left eye over a 6-month follow-up, and the right eye never showed any abnormality, except for a modest cataract, by any means of examination.

Conclusion:

Bilateral uveal melanocytic proliferation has been attributed to a paraneoplastic process, allegedly from a factor in the IgG fraction of the serum. However, unilateral involvement suggests that there are other factors involved in disease manifestation.
Trimodality therapy for resectable gastric cancer: analysis of the benefit in radiation
Authors: Thind Balkarn S. , Mullen Thomas D. , Healy Erin , Serrano Nicholas , Christensen Diana M. , Miller Trevor T. , Zeng Jing , Oelschlager Brant K. , Patel Shilpen A.
Published: December 2016

Background:

Gastric cancer is a common cause of cancer mortality worldwide, and due to its often advanced stage at the time of diagnosis, surgery alone is often inadequate treatment. Both chemotherapy (CH) and chemoradiation therapy (CHR) are used in the adjuvant setting and are both supported by randomized clinical trials. In this report, we compare the overall survival (OS), disease-free survival (DFS), and treatment toxicities of multimodal therapy with and without radiation.

Patients and methods:

Data from 193 patients diagnosed with stage IB-III gastric cancer treated with surgery (S group), surgery plus chemotherapy (S+CH group), or surgery plus chemoradiation (S+CHR group) were retrospectively analyzed. OS, DFS, and toxicities were compared in the various treatment modalities.

Results:

The S+CH (N=69) and S+CHR group (N=92) both had significant reduction in hazard ratio (HR) of death (HR, 0.24; P<0.001; HR, 0.33; P<0.001, respectively) when compared with the S group (N=32). Although S+CHR showed no significant benefit in OS or DFS (P=0.73, 0.16, respectively) when compared with S+CH, in a subgroup of patients with clinically lymph node–positive disease, S+CHR had significant improvement in DFS (HR, 1.83; P=0.047). Significantly higher rates of esophagitis were observed in the S+CHR, but no significant difference in grade 3 to 4 hematologic toxicities. One treatment related death was recorded in S+CH from postsurgical grade 5 sepsis. The clinical nodal classification was borderline significantly different between the S+CH and S+CHR groups (P=0.05) with a greater percentage of the S+CHR group being node positive.

Conclusions:

Multimodal therapy was associated with improved OS in our report when compared with surgery alone. Although patients who received CHR along with surgery did not have a significant difference in OS or DFS when compared with those receiving only chemotherapy with surgery, there was a difference in DFS in those patients who were clinically lymph node positive.
Primary surgical treatment of locally advanced breast cancer with heavy nodal involvement: a case report
Authors: Weledji Elroy P. , Elong Felix A.
Published: December 2016

Introduction:

Locally advanced breast cancer remains an important clinical problem, particularly in resource-poor settings. The prevalence is high in developing countries because of minimal breast awareness programmes, neglect, and the limited use of the multidisciplinary approach in management. Neoadjuvant chemotherapy is the mainstay of management, but the question as to whether primary surgical care could be used in resource-poor settings is of certain value and interest.

Case presentation:

We present the case of a 42-year-old African woman with a locally advanced carcinoma of the right breast and heavy nodal involvement only (T3, N2, M0). She underwent a simple mastectomy with en bloc lymphadenectomy to level II (axillary vein) followed by adjuvant radiotherapy to the mastectomy bed and systemic chemotherapy. There was no clinical evidence of local recurrence or distant metastases at 2 years’ follow-up.

Conclusions:

Primary surgical treatment may be acceptable in selected patients with locally advanced breast cancer. Further studies in the form of a clinical trial would ascertain the beneficial role of surgery in locally advanced breast cancer, especially in resource-poor settings.
Relationship of the Middle Ear Effusion Microbiome to Secretory Mucin Production in Pediatric Patients With Chronic Otitis Media
Authors: Krueger Anna , Val Stéphanie , Pérez-Losada Marcos , Panchapakesan Karuna , Devaney Joe , Duah Vanessa , DeMason Christine , Poley Marian , Rose Mary , Preciado Diego
Published: December 2016

Background:

Acute otitis media, an infection of the middle ear, can become chronic after multiple episodes. Microbial influence on chronic otitis media remains unclear. It has been reported that mucin glycoproteins are required for middle ear immune defense against pathogens. We aim to characterize the middle ear effusion (MEE) microbiome using high-throughput sequencing and assess potential associations in microbiome diversity with the presence of the secretory mucins MUC5B and MUC5AC. We hypothesize that MEEs containing MUC5B will exhibit a microbiome largely devoid of typical acute otitis media bacteria.

Methods:

Fifty-five MEEs from children undergoing myringotomy at Children’s National Health System were recovered. Mucin was semiquantitatively determined through Western blot analysis. DNA was subjected to 16S rRNA amplicon sequencing using the Illumina MiSeq platform. Raw data were processed in mothur (SILVA reference database). Alpha- and beta-diversity metrics were determined. Abundance differences between sample groups were estimated.

Results:

MUC5B was present in 94.5% and MUC5AC in 65.5% of MEEs. Sequencing revealed 39 genera with a relative abundance ≥0.1%. Haemophilus (22.54%), Moraxella (11.11%) and Turicella (7.84%) were the most abundant. Turicella and Pseudomonas proportions were greater in patients older than 24 months of age. In patients with hearing loss, Haemophilus was more abundant, while Turicella and Actinobacteria were less abundant. Haemophilus was also more abundant in samples containing both secretory mucins.

Conclusions:

The microbiome of MEEs from children with chronic otitis media differs according to specific clinical features, such as mucin content, age and presence of hearing loss. These associations provide novel pathophysiologic insights across the spectrum of otitis media progression.
Clinical and Virus Surveillance After the First Wheezing Episode
Authors: Turunen Riitta , Vuorinen Tytti , Bochkov Yury , Gern James , Jartti Tuomas
Published: December 2016

Background:

Susceptibility to rhinovirus (RV)-induced early wheezing episode has been recognized as an important risk factor for asthma, but the data on different RV species are limited. Our aim was to investigate the risk for recurrences in first-time wheezing children with special focus on RV species.

Methods:

First-time wheezing children (88 inpatients and 23 outpatients) were prospectively followed at 2-week, 2-month and 12-month time-points, and at first recurrence within 12 months. The respiratory virus etiology was analyzed using polymerase chain reaction. RV-positive samples were sequenced. The primary outcomes were time to a new physician-confirmed wheezing episode, time to a new RV-induced wheezing episode and time to the initiation of regular controller medication for asthma symptoms.

Results:

The median age of the children was 12 months (standard deviation, 6.0), 67% were males and 23% were sensitized. RV dominated in symptomatic and asymptomatic infections. Different RV strains were observed in 97% (67/69) of consecutive samples during follow-up. First-time wheezing children with RV-C and RV-A had an increased risk for a new physician-confirmed wheezing episode and a new RV-associated wheezing episode than non-RV group (all P < 0.05). Also, the risk for the initiation of regular controller medication was increased in RV-A and RV-C groups when compared with non-RV group (both P < 0.05).

Conclusions:

RV causes reinfections with different strains in small children after the first wheezing episode. Both RV-A and RV-C affected children have an increased risk for recurrence, especially RV associated, and initiation of regular controller medication than those with other viruses.
Epidemiology and Outcomes of Hospitalized Children With Necrotizing Soft-Tissue Infections
Authors: Totapally Balagangadhar R.
Published: December 2016

Objective:

The purpose of this study was to evaluate the epidemiology and outcome of hospitalized children with a diagnosis of necrotizing soft-tissue infections (NSTIs).

Methods:

Demographic and outcome data of children 1 month to 18 years of age with a diagnosis of NSTI (International Classification of Diseases, 9th revision diagnosis codes 728.86 and 729.4) were extracted from the Kids’ Inpatient Database 2009 and 2012. Univariate and multivariate analyses were done to determine the factors affecting mortality. The sample data were weighted to get national estimates.

Results:

A total of 446 children with NSTI (prevalence of 1.12/10,000 discharges) were included. Males comprised 54%. The median age was 10 (interquartile range 4–16) years. The mortality rate was 6%. In addition, 29.3% of children with NSTI were discharged to either skilled nursing facilities or to home health care compared with 4.5% of children without NSTI (odds ratio 8.9; 95% confidence interval 7.3–10.9;P< 0001). A bacterial infection was reported in 72.1% of children. An infection withStaphylococcus,Streptococcus, Gram-negative bacteria, anaerobic bacteria, methicillin-resistantStaphylococcus areusand polymicrobia was present in 34.5%, 21.8%, 8.6%, 3.9%, 18.7% and 13.6% of cases, respectively. A compartment syndrome, severe sepsis/septic shock and toxic shock were documented in 4.4%, 22.2% and 3.2% of the cases, respectively. Severe sepsis/septic shock, the need for mechanical ventilation and Hispanic race were associated with increased mortality, whereas skin/muscle surgery was associated with lower mortality.

Conclusions:

NSTI in children is associated with high morbidity. The mortality is higher with the presence of severe sepsis/septic shock and among Hispanics and lower with surgical intervention.
Clinical and Bacterial Risk Factors for Mortality in Children With Carbapenem-resistant Enterobacteriaceae Bloodstream Infections in India
Authors: Nabarro Laura E. B. , Shankar Chaitra , Pragasam Agila K. , Mathew Georgekutty , Jeyaseelan Visali , Veeraraghavan Balaji , Verghese Valsan P.
Published: December 2016

Background:

Carbapenem-resistant Enterobacteriaceae (CRE) are an increasing cause of nosocomial infection in hospitalized children worldwide. Few studies have investigated risk factors for mortality in children with CRE bloodstream infection (BSI). Data are particularly scarce in areas where NDM and OXA carbapenemases predominate. Here, we investigate mortality rates, clinical and microbiologic risk factors for mortality in 50 pediatric patients with CRE BSI in India.

Methods:

Children younger than 17 years old with meropenem-resistant Klebsiella pneumoniae or Escherichia coli isolated from blood culture in 2014 and 2015 were identified from laboratory records. Clinical records were systematically reviewed for each child to establish mortality at 30 days and clinical details. Bacterial isolates were subjected to meropenem E test and multiplex polymerase chain reaction to determine carbapenemase gene. Data were analyzed to establish clinical and bacterial risk factors for mortality.

Results:

All CRE BSI were hospital-acquired or associated with healthcare. A total of 84% of children had an underlying comorbidity and 46% had a malignancy. K. pneumoniae was the most common bacteria isolated; NDM was the most common carbapenemase gene detected. The mortality rate was 52%. Significant risk factors for mortality included intensive care admission, intubation, inotropic support and respiratory source. Failure to clear bacteremia and a minimum inhibitory concentration > 8 mg/L for the isolate was associated with a statistically significant increase in mortality. Mortality rates were significantly lower when two or more effective drugs were used in combination.

Conclusions:

CRE BSI affects children with multiple comorbidities and repeated admissions to hospital. The mortality rate is high; combination therapy may be beneficial.
Nasal Airway Microbiota Profile and Severe Bronchiolitis in Infants
Authors: Hasegawa Kohei , Linnemann Rachel W. , Mansbach Jonathan M. , Ajami Nadim J. , Espinola Janice A. , Petrosino Joseph F. , Piedra Pedro A. , Stevenson Michelle D. , Sullivan Ashley F. , Thompson Amy D. , Camargo Carlos A.
Published: December 2016

Background:

Little is known about the relationship of airway microbiota with bronchiolitis in infants. We aimed to identify nasal airway microbiota profiles and to determine their association with the likelihood of bronchiolitis in infants.

Methods:

A case-control study was conducted. As a part of a multicenter prospective study, we collected nasal airway samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 110 age-matched healthy controls. By applying 16S ribosomal RNA gene sequencing and an unbiased clustering approach to these 150 nasal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis.

Results:

Overall, the median age was 3 months and 56% were male. Unbiased clustering of airway microbiota identified 4 distinct profiles: Moraxella-dominant profile (37%), Corynebacterium/Dolosigranulum-dominant profile (27%), Staphylococcus-dominant profile (15%) and mixed profile (20%). Proportion of bronchiolitis was lowest in infants with Moraxella-dominant profile (14%) and highest in those with Staphylococcus-dominant profile (57%), corresponding to an odds ratio of 7.80 (95% confidence interval, 2.64–24.9; P < 0.001). In the multivariable model, the association between Staphylococcus-dominant profile and greater likelihood of bronchiolitis persisted (odds ratio for comparison with Moraxella-dominant profile, 5.16; 95% confidence interval, 1.26–22.9; P = 0.03). By contrast, Corynebacterium/Dolosigranulum-dominant profile group had low proportion of infants with bronchiolitis (17%); the likelihood of bronchiolitis in this group did not significantly differ from those with Moraxella-dominant profile in both unadjusted and adjusted analyses.

Conclusions:

In this case-control study, we identified 4 distinct nasal airway microbiota profiles in infants. Moraxella-dominant and Corynebacterium/Dolosigranulum-dominant profiles were associated with low likelihood of bronchiolitis, while Staphylococcus-dominant profile was associated with high likelihood of bronchiolitis.
Virologic Response to First-line Efavirenz- or Nevirapine-based Antiretroviral Therapy in HIV-infected African Children
Authors: Kekitiinwa Adeodata , Szubert Alexander J. , Spyer Moira , Katuramu Richard , Musiime Victor , Mhute Tawanda , Bakeera-Kitaka Sabrina , Senfuma Oscar , Walker Ann Sarah , Gibb Diana M.
Published: December 2016

Background:

Poorer virologic response to nevirapine- versus efavirenz-based antiretroviral therapy (ART) has been reported in adult systematic reviews and pediatric studies.

Methods:

We compared drug discontinuation and viral load (VL) response in ART-naïve Ugandan/Zimbabwean children ≥3 years of age initiating ART with clinician-chosen nevirapine versus efavirenz in the ARROW trial. Predictors of suppression <80, <400 and <1000 copies/mL at 36, 48 and 144 weeks were identified using multivariable logistic regression with backwards elimination (P = 0.1).

Results:

A total of 445 (53%) children received efavirenz and 391 (47%) nevirapine. Children receiving efavirenz were older (median age, 8.6 vs. 7.5 years nevirapine, P < 0.001) and had higher CD4% (12% vs. 10%, P = 0.05), but similar pre-ART VL (P = 0.17). The initial non-nucleoside-reverse-transcriptase-inhibitor (NNRTI) was permanently discontinued for adverse events in 7 of 445 (2%) children initiating efavirenz versus 9 of 391 (2%) initiating nevirapine (P = 0.46); at switch to second line in 17 versus 23, for tuberculosis in 0 versus 26, for pregnancy in 6 versus 0 and for other reasons in 15 versus 5. Early (36–48 weeks) virologic suppression <80 copies/mL was superior with efavirenz, particularly in children with higher pre-ART VL (P = 0.0004); longer-term suppression was superior with nevirapine in older children (P = 0.05). Early suppression was poorer in the youngest and oldest children, regardless of NNRTI (P = 0.02); longer-term suppression was poorer in those with higher pre-ART VL regardless of NNRTI (P = 0.05). Results were broadly similar for <400 and <1000 copies/mL.

Conclusion:

Short-term VL suppression favored efavirenz, but long-term relative performance was age dependent, with better suppression in older children with nevirapine, supporting World Health Organization recommendation that nevirapine remains an alternative NNRTI.
Despite Access to Antiretrovirals for Prevention and Treatment, High Rates of Mortality Persist Among HIV-infected Infants and Young Children
Authors: Abrams Elaine J. , Woldesenbet Selamawit , Soares Silva Juliana , Coovadia Ashraf , Black Viviane , Technau Karl-Günter , Kuhn Louise
Published: December 2016

Background:

Outcomes of HIV-infected children before widespread use of antiretroviral therapy (ART) for treatment and prevention of mother-to-child transmission (PMTCT) have been well characterized but less is known about children who acquire HIV infection in the context of good ART access.

Methods:

We enrolled newly diagnosed HIV-infected children ≤24 months of age at 3 hospitals and 2 clinics in Johannesburg, South Africa. We report ART initiation and mortality rates during 6 months from enrollment and factors associated with mortality.

Results:

Of 272 children enrolled, median age 6.1 months, 69.5% were diagnosed during hospitalization. By 6 months postenrollment, 53 (19.5%) died and 73 (26.8%) were lost-to-follow-up. Using Kaplan–Meier analysis, the probability of death by 6 months after enrollment was 23.5%. The median age of death was 9.1 months [95% confidence interval (CI): 8.6–12.0]. Overall, 226 (83%) children initiated ART which was associated with a 71% reduction in risk of death [hazard ratio (HR) = 0.29 (95% CI: 0.15–0.58)]. In multivariable analysis of infant factors, weight-for-age Z score < −2 standard deviation (SD) [HR = 2.43 (95% CI: 1.03–5.73)], CD4 <20% [HR = 3.29 (95% CI: 1.60–6.76)] and identification during hospitalization [HR = 2.89 (95% CI: 1.16–7.25)] were independently associated with mortality. In multivariable analysis of maternal factors, CD4 ≤350/no maternal ART was associated with increased mortality risk [HR = 2.57 (95% CI: 1.19–5.59)] versus CD4 >350/no maternal ART; exposure to maternal/infant antiretrovirals for PMTCT was associated with reduced mortality risk [HR = 0.53 (95% CI: 0.28–0.99)] versus no PMTCT.

Conclusions:

ART initiation is highly protective against death in young children. However, despite improved access to ART, young children remain at risk for early death; innovative approaches to rapidly diagnose and initiate treatment as early in life as possible are needed.
Highlights From the 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society on Management of Adults With Hospital-Acquired and Ventilator-Associated Pneumonia
Authors: File Thomas M.
Published: December 2016

Hospital-acquired pneumonia and ventilator-associated pneumonia are among the most serious hospital-associated infections. The Infectious Diseases Society of America and the American Thoracic Society have published an update of guidelines for these infections. This updated guideline provides new recommendations for appropriate management. Important highlights include elimination of health care–associated pneumonia; continued recommendation of a clinical diagnosis as compared with surveillance definition for decision to initiate antimicrobial therapy for suspected infection; specific antimicrobial recommendations for empiric and pathogen-directed therapy; use of pharmacodynamic dosing; and use of procalcitonin to assist with duration decision with 7 days as general recommendation for all pathogens.
Enhanced delivery of IL-1 receptor antagonist to the central nervous system as a novel anti–transferrin receptor-IL-1RA fusion reverses neuropathic mechanical hypersensitivity
Authors: Webster Carl I. , Hatcher Jon , Burrell Matthew , Thom George , Thornton Peter , Gurrell Ian , Chessell Iain
Published: December 2016

Neuropathic pain is a major unmet medical need, with only 30% to 35% of patients responding to the current standard of care. The discovery and development of novel therapeutics to address this unmet need have been hampered by poor target engagement, the selectivity of novel molecules, and limited access to the relevant compartments. Biological therapeutics, either monoclonal antibodies (mAbs) or peptides, offer a solution to the challenge of specificity as the intrinsic selectivity of these kinds of molecules is significantly higher than traditional medicinal chemistry–derived approaches. The interleukin-1 receptor system within the spinal cord has been implicated in the amplification of pain signals, and its central antagonism provides relief of neuropathic pain. Targeting the IL-1 system in the spinal cord with biological drugs, however, raises the even greater challenge of delivery to the central compartment. Targeting the transferrin receptor with monoclonal antibodies has proved successful in traversing the endothelial cell–derived blood–brain barrier and delivering proteins to the central nervous system. In this study, we describe a novel construct exemplifying an engineered solution to overcome these challenges. We have generated a novel anti–transferrin receptor-interleukin-1 receptor antagonist fusion that transports to the central nervous system and delivers efficacy in a model of nerve ligation–induced hypersensitivity. Approaches such as these provide promise for novel and selective analgesics that target the central compartment.
Light-Driven Contact Hearing Aid for Broad-Spectrum Amplification: Safety and Effectiveness Pivotal Study
Authors: Gantz Bruce J. , Perkins Rodney , Murray Michael , Levy Suzanne Carr , Puria Sunil
Published: December 2016

Objective:

Demonstrate safety and effectiveness of the light-driven contact hearing aid to support FDA clearance.

Study Design:

A single-arm, open-label investigational-device clinical trial.

Setting:

Two private-practice and one hospital-based ENT clinics.

Patients:

Forty-three subjects (86 ears) with mild-to-severe bilateral sensorineural hearing impairment.

Intervention:

Bilateral amplification delivered via a light-driven contact hearing aid comprising a Tympanic Lens (Lens) with a customized platform to directly drive the umbo and a behind-the-ear sound processor (Processor) that encodes sound into light pulses to wirelessly deliver signal and power to the Lens.

Main Outcome Measures:

The primary safety endpoint was a determination of “no change” (PTA4 < 10 dB) in residual unaided hearing at the 120-day measurement interval. The primary efficacy endpoint was improvement in word recognition using NU-6 at the 30-day measurement interval over the baseline unaided case. Secondary efficacy endpoints included functional gain from 2 to 10 kHz and speech-in-noise improvement over the baseline unaided case using both omnidirectional and directional microphones.

Results:

The results for the 86 ears in the study determined a mean change of −0.40 dB in PTA4, indicating no change in residual hearing (p < 0.0001). There were no serious device- or procedure-related adverse events, or unanticipated adverse events. Word recognition aided with the Earlens improved significantly (p < 0.0001) over the unaided performance, by 35% rationalized arcsine units on average. Mean functional gain was 31 dB across 2 to 10 kHz. The average speech-recognition threshold improvement over the unaided case for the Hearing in Noise Test was 0.75 dB (p = 0.028) and 3.14 dB (p < 0.0001) for the omnidirectional and directional microphone modes, respectively.

Conclusion:

The safety and effectiveness data supported a de novo 510(k) submission that received clearance from the FDA.
Surgical Technique for Ventricular Device Exchange: From HeartMate II to HVAD
Authors: Gallo Michele , Trivedi Jaimin R. , Sobieski Michael A. , Massey Todd H. , Cheng Allen , Slaughter Mark S.
Published: December 2016

Implantable continuous-flow left ventricular assist devices (LVADs) have improved the survival of end-stage heart failure patients. Recent studies have shown an increased occurrence of device replacement in the axial flow pumps particularly for thrombosis. In some patients, to try and avoid recurrent pump thrombosis, it might be advantageous to switch from the axial flow LVAD to a newer generation centrifugal flow LVAD. Technically, this requires some adaption of the LVAD inflow and outflow connections. We describe our technique and outcomes in patients who underwent the conversion from an axial flow LVAD to a centrifugal flow LVAD.
Worldwide Experience with the Syncardia Total Artificial Heart in the Pediatric Population
Authors: Morales David L. S. , Lorts Angela , Rizwan Raheel , Zafar Farhan , Arabia Francisco A. , Villa Chet R.
Published: December 2016

Individual centers have documented the use of the Syncardia Total Artificial Heart (TAH) in adolescents with heart failure; however, the number of patients at any given center is small. Herein, we describe the worldwide experience for all patients ≤21 years old supported with the TAH between May 2005 and May 2015 (n = 43). The number of patients experiencing a positive outcome at 60, 90, and 120 days were 30 (70%), 27 (63%), and 25 (58%), respectively. Successful bridge to transplantation varied by diagnosis, but outcomes reported are similar to adults supported with the TAH or biventricular assist devices.
Outcomes and Trends of Ventricular Assist Device Selection in Children with End-Stage Heart Failure
Authors: Miller Jacob R. , Lancaster Timothy S. , Epstein Deirdre J. , DuPont Nicholas C. , Simpson Kathleen E. , Castleberry Chesney , Canter Charles E. , Eghtesady Pirooz , Boston Umar S.
Published: December 2016

We aimed to examine trends in ventricular assist device (VAD) selection, continuous flow devices (CFD) versus pulsatile flow devices (PFD), and their associated outcomes in children eligible for both device types. To accomplish this, the United Network for Organ Sharing database was reviewed for pediatric patients listed for heart transplant (HT) from January 2007 to June 2014. Patients were included if a durable VAD was present at wait listing or when removed from the waiting list and who met size eligibility for a CFD (BSA > 1.0 m2). In total, 253 patients met inclusion criteria, 144 (57%) CFD and 109 (43%) PFD. Device type varied significantly based on year with CFD increasing from 11% in 2007 to 88% in 2014 (p < 0.01). PFD patients were younger, had a lower BSA, and an increased rate of extracorporeal membrane oxygenation and biventricular assist device support at listing. Survival to transplant or recovery was similar for CFDs and PFDs (96 vs. 94%; p = 0.57), as was the post-HT survival, 95% for both device types. Despite PFD patients having more risk factors for a poor outcome, survival was similar between device types. Even so, there is a dramatic trend toward CFD utilization in patients who are large enough to support one.
The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders
Authors: Farmer Adam D. , Ruffle James K. , Aziz Qasim
Published: December 2016

The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.
Covert Hepatic Encephalopathy
Authors: Shaw Jawaid , Bajaj Jasmohan S.
Published: December 2016

Liver cirrhosis is a public health problem and hepatic encephalopathy is one of its main complications, which can be either overt meaning thereby evident and readily diagnosed, or covert/minimal (covert hepatic encephalopathy—CHE) needing psychometric testing for diagnosis. Patients with CHE hepatic encephalopathy have deficits in multiple domains including visuospatial assessment, attention, response inhibition, working memory, along with psychomotor speed to name a few areas. These patients have poor navigational skills, get fatigued easily, and demonstrate poor insight into their driving deficits. The combination of all these leads them to have poor driving skills leading to traffic violations and crashes as demonstrated not only on the simulation testing but also in real-life driving events. There are multiple psychometric tests for CHE testing but these are not easily available and there is no uniform consensus on the gold standard testing as of yet. It does not automatically connote that all patients who test positive on driving simulation testing are unfit to drive. The physicians are encouraged to take driving history from the patient and the caregivers on every encounter and focus their counseling efforts more on patients with recent history of traffic crashes, with abnormal simulation studies and history of alcohol cessation within last year. As physicians are not trained to determine fitness to drive, their approach toward CHE patients in regards to driving restrictions should be driven by ethical principles while as respecting the local laws.
Within-Stool and Within-Day Sample Variability of Fecal Calprotectin in Patients With Inflammatory Bowel Disease
Authors: Du Lillian , Foshaug Rae , Huang Vivian W. , Kroeker Karen I. , Dieleman Levinus A. , Halloran Brendan P. , Wong Karen , Fedorak Richard N.
Published: December 2016

Background and Goals:

The use of fecal calprotectin (FC) as a stool biomarker for differentiating inflammatory bowel disease (IBD) from IBS has been well validated, and there is a strong correlation between FC and the presence of endoscopic inflammatory lesions. However, recent studies have demonstrated intraindividual sample variability in patients with IBD, possibly limiting the reliability of using a single sample for monitoring disease activity. Our aim was to assess the within-stool and within-day sample variability of FC concentrations in patients with IBD.

Study:

We examined a cross-sectional cohort of 50 adult IBD patients. Eligible patients were instructed to collect 3 samples from different parts of the stool from their first bowel movement of the day and 3 samples from each of up to 2 additional bowel movements within 24 hours. FC concentrations were measured by a rapid, quantitative point-of-care test using lateral flow technology (Quantum Blue). Descriptive statistics were used to assess FC variability within a single bowel movement and between different movements at different FC positivity cutoffs.

Results:

Within a single bowel movement, there was clinically significant sample variability ranging from 8% to 23% depending on the time of the day or on the FC positivity cutoff value. Between bowel movements, there was clinically significant sample variability ranging from 13% to 26% depending on the FC positivity cutoff.

Conclusions:

Considering a single FC sample, the first sample of the day with an FC positivity cutoff of 250 μg/g provided the most reliable indication of disease activity.
There is Significant Practice Pattern Variability in the Management of the Hospitalized Ulcerative Colitis Patient at a Tertiary Care and IBD Referral Center
Authors: Shah Shailja C. , Naymagon Steven , Cohen Benjamin L. , Sands Bruce E. , Dubinsky Marla C.
Published: December 2016

Background and Goals:

Despite published clinical guidelines, substantive data underlying the approach to the management of hospitalized ulcerative colitis (UC) patients failing outpatient therapy are lacking. Variability in practice is therefore not uncommon and may impact clinical outcomes. The degree of variability, however, is not well-studied. Our aim was to evaluate variability in management of the hospitalized UC patient to inform future efforts targeting care optimization for this high-risk population.

Study:

An internet survey was distributed among inflammatory bowel disease providers, which included: (1) nonvignette-based questions assessing provider demographics, experience, and practice setting; (2) diagnostic and therapeutic practice patterns based on a vignette of a hospitalized UC patient. Descriptive and univariate analyses were performed.

Results:

Ninety-one percent of eligible individuals were included. Nearly 97% endorsed confidence in management of hospitalized UC patients. In general, 83% initiate intravenous corticosteroids (IVCS) as initial therapy, whereas 17% initiate infliximab (IFX) (+/−IVCS). At IVCS failure in the vignette, 74% initiated IFX, 15% increased IVCS dose, 7% initiated cyclosporine, and 4% chose colectomy. Of those choosing IFX, 65% chose 5 mg/kg as the initial dose, whereas the remainder chose 10 mg/kg. Twenty-eight percent gave an additional IFX 5 mg/kg and 7% gave an additional 10 mg/kg dose to the patient in the vignette not responding to 5 mg/kg.

Conclusions:

Even among experienced inflammatory bowel disease providers, there is significant practice pattern variability in the management of hospitalized UC patients. Future efforts should target this variability. Adjunctively, prospective trials are needed to guide appropriate therapeutic algorithms, especially with respect to positioning and optimally dosing IFX in this population.
Etiology and Pathogenesis of Idiopathic Achalasia
Authors: Pressman Amanda , Behar Jose
Published: December 2016

This review examines the etiology and pathogenesis of idiopathic achalasia. This disease is clinically characterized by dysphagia of solids and liquids due to the presence of simultaneous or absent esophageal contractions and impaired or absent relaxation of the lower esophageal sphincter. It includes a review of (a) etiology and pathogenesis of this inflammatory process that damage the ganglion cells of the Auerbach plexus that is limited to the esophagus; (b) genetic abnormalities and polymorphisms associated with this disease that may help explain its heterogeneity expressed by the different motility abnormalities of its phenotypes as well as differences in its clinical progression. These different genetic abnormalities may be responsible for the slow progression of types I or II phenotypes; (c) indirect evidence of viruses present in these patients that may initiate its development; (d) the abnormalities of the muscle layer that may be responsible for the dilation of the body of the esophagus that ultimately causes the sigmoid-like esophagus in the very last phase of this disease. This progression to the end-stage phase tends to occur in about 5% of patients. And, (e) the chronic inflammatory abnormalities in the squamous mucosa that may be the cause of the dysplastic and neoplastic changes that may lead to squamous cell carcinoma whose incidence in this disease is increased. These mucosal abnormalities are usually present in patients with markedly dilated body of the esophagus and severe food stasis.
Diabetes Mellitus is Associated With Mortality in Acute Pancreatitis
Authors: Huh Ji Hye , Jeon Hosung , Park Sun Min , Choi EunHee , Lee Geun Sook , Kim Jae Woo , Lee Kyong Joo
Published: December 2016

Background and Aim:

Predicting severe pancreatitis is important for early aggressive management of patients with acute pancreatitis (AP). Despite the established role of diabetes mellitus (DM) in the risk of AP, the impact of DM on the clinical outcome in AP has not been fully elucidated. The objective of this study was to assess the risk of mortality and severity in AP among patients with type-2 DM.

Methods:

Patients diagnosed with first attacks of AP were enrolled from January 2013 to June 2015.

Results:

A total of 201 patients (63.2% male, mean age, 59.4 y) with AP were included. Etiologies included gallstones (51.2%), alcohol (37.3%), hypertriglyceridemia (2%), and idiopathic causes (9.5%). There were 54 AP patients (26.9%) with type-2 DM. Severity indices in AP, such as Atlanta Classification (severe), Ranson score, and Bedside Index of Severity in Acute Pancreatitis, were higher in subjects with DM than those without DM. Prevalence of intensive care unit admission and mortality were higher in AP patients with DM compared with those without DM. The association between DM and increased risk of mortality in AP remained statistically significant even after adjustments for confounding factors and Atlanta Classification (odds ratio, 7.76, 95% confidence interval, 1.26-47.63, P=0.027).

Conclusions:

Type-2 DM was associated with severity and increased mortality in patients with AP. Our findings provide evidence of the potential role of DM in the pathogenesis and management of severe AP.
EUS-guided Versus Percutaneous Gallbladder Drainage
Authors: Tyberg Amy , Saumoy Monica , Sequeiros Enrique V. , Giovannini Marc , Artifon Everson , Teoh Anthony , Nieto Jose , Desai Amit P. , Kumta Nikhil A. , Gaidhane Monica , Sharaiha Reem Z. , Kahaleh Michel
Published: December 2016

Background and Aims:

Endoscopic ultrasound–guided drainage (EUS-GLB) is a minimally invasive option for patients with cholecystitis who are poor surgical candidates. Compared with percutaneous drainage (PC-GLB), earlier studies have demonstrated similar efficacy with improved quality of life. We present a multicenter, international experience comparing PC-GLB and EUS-GLB in nonsurgical patients with cholecystitis.

Methods:

All patients who underwent either PC-GLB drainage or EUS-GLB drainage from 7 centers between January 2010 and December 2015 were included. Technical success was defined as successful placement of a catheter or stent into the gallbladder. Clinical success was defined as resolution of clinical symptoms after intervention. Adverse events, length of stay, and the need for repeat interventions and/or hospitalizations were recorded for all patients.

Results:

A total of 155 patients were included (mean age 74±14.24 y; range, 31 to 96; 56% male). Forty-two patients underwent EUS-GLB and 113 patients underwent PC-GLB. Technical success was achieved in 40 patients (95%) in the EUS-GLB group and 112 patients (99%) in the PC-GLB group (P=0.179). Clinical success was achieved in 40 patients (95%) in the EUS-GLB group and 97 patients (86%) in the PC-GLB group (P=0.157). There was no difference in hospital readmission rates between the 2 groups (14% vs. 24%; P=0.194). However, there was significantly higher number of patients requiring repeat interventions in the PC-GLB group (n=28, 24%) compared with the EUS-GLB group (n=4, 10%) (P=0.037). There was no difference in adverse events between the 2 groups.

Conclusions:

EUS-GLB is safe and efficacious, with comparable technical and clinical success rates and no difference in adverse events. In addition, EUS-GLB offers a potential cost-saving benefit and morbidity benefit by demonstrating a decreased number of repeat interventions.
Precursors of pancreatic cancer
Authors: Frič Přemysl , Škrha Jan , Šedo Aleksi , Bušek Petr , Laclav Martin , Bunganič Bohuš , Zavoral Miroslav
Published: December 2016

Pancreatic cancer (PC) behaves very differently in comparison with other malignancies. Its incidence has been increasing continuously; mortality has not decreased, the diagnosis is frequently late, radical surgery is performed only in 15–20% of patients, and chemotherapy is only palliative. PC occurs in three different forms. Sporadic PC accounts for 90% of all PCs. Its most frequent form is the pancreatic ductal adenocarcinoma. The remaining 10% constitute two minority groups: familial PC (7%) and PC as a manifestation of a genetic cancer syndrome (3%). PCs are preceded by a precancerous lesion (precursor). At present, six different precursors are known. They have different histomorphological characteristics and malignant potential. The recognition and correct interpretation of individual precursors influences adequate clinical decision-making. The publication surveys the present knowledge of individual precursors and their role in the early pancreatic carcinogenesis.
Insulin resistance is associated with elevated transaminases and low aspartate aminotransferase/alanine aminotransferase ratio in young adults with normal weight
Authors: Simental-Mendía Luis E. , Rodríguez-Morán Martha , Gómez-Díaz Rita , Wacher Niels H. , Rodríguez-Hernández Heriberto , Guerrero-Romero Fernando
Published: December 2016

Objective

The aim of this study is to determine whether insulin resistance is associated with elevation of transaminases levels and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio in normal-weight healthy young adults.

Participants and methods

Apparently healthy nonpregnant women and men, aged 18–23 years, were enrolled in a cross-sectional study. According to the homeostasis model assessment of insulin resistance, the participants were allocated into groups of patients with (>2.5) and without (≤2.5) insulin resistance. Normal weight was defined by BMI of at least 18.5 and less than 25.0 kg/m2. A multiple logistic regression analysis was carried out to determine the association between insulin resistance and elevated transaminases and AST/ALT ratio of 1 or less.

Results

A total of 1732 young adults were enrolled and allocated into groups with (n=287) and without (n=1445) insulin resistance. The prevalence of insulin resistance was 16.6% in the overall population. The multivariate logistic regression analysis adjusted by age, sex, waist circumference, and BMI indicated that the odds ratio (OR) between insulin resistance and elevated ALT concentrations is 1.65 [95% confidence interval (CI): 1.04–2.62, P=0.03], for AST/ALT ratio lower than 1 OR is 1.69 (95% CI: 1.27–2.26, P<0.001), and for elevated AST levels OR is 1.31 (95% CI: 0.71–2.43, P=0.377).

Conclusion

The results of the present study suggest that insulin resistance is significantly associated with elevated ALT levels and AST/ALT ratio of lower than 1, but not with elevated AST levels.