bluuebunny/crossref_metadata_2025 huggingface dataset:
The Sensitivity of the Electrically Stimulated Auditory Nerve to Amplitude Modulation Cues Declines With Advanced Age
Authors: Riggs William J. , Vaughan Chloe , Skidmore Jeffrey , Conroy Sara , Pellittieri Angela , Carter Brittney L. , Stegman Curtis J. , He Shuman
Published: April 2021

Objectives:

This study aimed to investigate effects of aging and duration of deafness on sensitivity of the auditory nerve (AN) to amplitude modulation (AM) cues delivered using trains of biphasic pulses in adult cochlear implant (CI) users.

Design:

There were 21 postlingually deaf adult CI users who participated in this study. All study participants used a Cochlear Nucleus device with a full electrode array insertion in the test ear. The stimulus was a 200-ms pulse train with a pulse rate of 2000 pulses per second. This carrier pulse train was sinusodially AM at four modulation rates (20, 40, 100, 200 Hz). The peak amplitude of the modulated pulse train was the maximum comfortable level (i.e., C level) measured for the carrier pulse train. The electrically evoked compound action potential (eCAP) to each of the 20 pulses selected over the last two AM cycles were measured. In addition, eCAPs to single pulses were measured with the probe levels corresponding to the levels of 20 selected pulses from each AM pulse train. There were seven electrodes across the array evaluated in 16 subjects (i.e., electrodes 3 or 4, 6, 9, 12, 15, 18, and 21). For the remaining five subjects, 4 to 5 electrodes were tested due to impedance issues or time constraints. The modulated response amplitude ratio (MRAR) was calculated as the ratio of the difference in the maximum and the minimum eCAP amplitude measured for the AM pulse train to that measured for the single pulse, and served as the dependent variable. Age at time of testing and duration of deafness measured/defined using three criteria served as the independent variables. Linear Mixed Models were used to assess the effects of age at testing and duration of deafness on the MRAR.

Results:

Age at testing had a strong, negative effect on the MRAR. For each subject, the duration of deafness varied substantially depending on how it was defined/measured, which demonstrates the difficulty of accurately measuring the duration of deafness in adult CI users. There was no clear or reliable trend showing a relationship between the MRAR measured at any AM rate and duration of deafness defined by any criteria. After controlling for the effect of age at testing, MRARs measured at 200 Hz and basal electrode locations (i.e., electrodes 3 and 6) were larger than those measured at any other AM rate and apical electrode locations (i.e., electrodes 18 and 21)

Conclusions:

The AN sensitivity to AM cues implemented in the pulse-train stimulation significantly declines with advanced age. Accurately measuring duration of deafness in adult CI users is challenging, which, at least partially, might have accounted for the inconclusive findings in the relationship between the duration of deafness and the AN sensitivity to AM cues in this study.
Longer Cochlear Implant Experience Leads to Better Production of Mandarin Tones for Early Implanted Children
Authors: Tang Ping , Yuen Ivan , Xu Rattanasone Nan , Gao Liqun , Demuth Katherine
Published: April 2021

Objectives:

Children with cochlear implants (CIs) face challenges in acquiring tones, since CIs do not transmit pitch information effectively. It has been suggested that longer CI experience provides additional benefits for children implanted early, enabling them to achieve language abilities similar to that of normal-hearing (NH) children (Colletti 2009). Mandarin is a tonal language with four lexical tones and a neutral tone (T0), characterized by distinct pitch and durational patterns. It has been suggested that early implantation (i.e., before 2 years) greatly benefits the acquisition of Mandarin tones by children with CIs (Tang et al. 2019c). In this study, we extend those findings to investigate the effect of CI experience on the acquisition of Mandarin tones for children implanted early. We asked the extent to which they were able to produce distinct pitch and durational patterns of both lexical tones and T0 as a function of CI experience, and the extent to which their tonal productions were acoustically like that of NH children.

Design:

Forty-four NH 3-year olds and 28 children implanted with CIs between 1 and 2 years, aged 3 to 7, were recruited. The children with CIs were grouped according to the length of CI experience: 3 to 6 years, 2 to 3 years, and 1 to 2 years. Lexical tone and T0 productions were elicited using a picture-naming task. Tonal productions from the children with CIs were acoustically analyzed and compared with those from the NH children.

Results:

Children with 3 to 6 years of CI experience were able to produce distinct pitch and durational patterns for both lexical tones and T0, with NH-like acoustic realizations. Children with 2 to 3 years of CI experience were also able to produce the expected tonal patterns, although their productions were not yet NH-like. Those with only 1 to 2 years of CI experience, however, were not yet able to produce the distinct acoustic patterns for either lexical tones or T0.

Conclusions:

These results provide acoustic evidence demonstrating that, when Mandarin-speaking children are implanted before the age of 2, only those with 3 to 6 years of experience were able to produce NH-like tones, including both lexical tone and T0. Children with shorter CI experience (less than 3 years) were unable to produce distinct acoustic patterns for the different tones. This suggests that at least 3 years of CI experience is still needed for early implanted children to acquire tonal distinctions similar to those of NH 3-year olds.
Association Between the Right Ear Advantage in Dichotic Listening and Interaural Differences in Sensory Processing at Lower Levels of the Auditory System in Older Adults
Authors: Ianiszewski Alejandro , Fuente Adrian , Gagné Jean-Pierre
Published: April 2021

Objective:

Current evidence suggests that an enhanced right ear advantage (REA) in dichotic listening (DL) among older adults may originate from age-related structural changes in the corpus callosum and age-related decline in cognitive processes. Less is known about the effect of information processing at lower portions of the auditory system on DL performance. The present study investigates whether interaural differences (ID) in sensory processing at lower levels of the auditory system are associated with the magnitude of the REA in DL among older adults.

Design:

Sixty-eight older adults participated in the study. Participants were assessed with a DL test using nonforced (NF) and forced attention paradigms. Hearing sensitivity, transient-evoked otoacoustic emission (TEOAE), contralateral suppression of TEOAE, a proxy measure of medial olivocochlear activation, and auditory brainstem response to speech stimuli (speech-ABR) were tested in both ears separately. The ID in sensory processing at lower levels of the auditory system was derived by calculating the difference between the RE and LE for each auditory measure. Bivariate and multivariate regression models were performed. One multivariate model for each DL paradigm (NF and forced attention) was independently constructed. Measures of cognitive speed of processing and cognitive flexibility were accounted for in the regression models.

Results:

For both multivariate regression models, ID in pure-tone thresholds and ID in MOC suppression of TEOAE were significantly associated with the magnitude of the REA for DL among older adults. Cognitive measures of speed of processing and cognitive flexibility also contributed to the magnitude of the REA.

Conclusion:

These results suggest that ID in sensory processing at lower levels of the auditory system account, at least in part, for the increased magnitude of the REA in DL among older adults.
Tinnitus and Its Central Correlates: A Neuroimaging Study in a Large Aging Population
Authors: Oosterloo Berthe C. , Croll Pauline H. , Goedegebure André , Roshchupkin Gennady V. , Baatenburg de Jong Robert J. , Ikram M. Arfan , Vernooij Meike W.
Published: April 2021

Objectives:

To elucidate the association between tinnitus and brain tissue volumes and white matter microstructural integrity.

Design:

Two thousand six hundred sixteen participants (mean age, 65.7 years [SD: 7.5 years]; 53.9% female) of the population-based Rotterdam Study underwent tinnitus assessment (2011 to 2014) and magnetic resonance imaging of the brain (2011 to 2014). Associations between tinnitus (present versus absent) and total, gray, and white matter volume and global white matter microstructure were assessed using multivariable linear regression models adjusting for demographic factors, cardiovascular risk factors, depressive symptoms, Mini-Mental State Examination score, and hearing loss. Finally, potential regional gray matter density and white matter microstructural volume differences were assessed on a voxel-based level again using multivariable linear regression.

Results:

Participants with tinnitus (21.8%) had significantly larger brain tissue volumes (difference in SD, 0.09; 95% confidence interval, 0.06 to 0.13), driven by larger white matter volumes (difference, 0.12; 95% confidence interval, 0.04 to 0.21) independent of hearing loss. There was no association between tinnitus and gray matter volumes nor with global white matter microstructure. On a lobar level, tinnitus was associated with larger white matter volumes in each lobe, not with gray matter volume. Voxel-based results did not show regional specificity.

Conclusions:

We found that tinnitus in older adults was associated with larger brain tissue volumes, driven by larger white matter volumes, independent of age, and hearing loss. Based on these results, it may be hypothesized that tinnitus potentially has a neurodevelopmental origin in earlier life independent of aging processes.
The Presence of Another Individual Influences Listening Effort, But Not Performance
Authors: Pielage Hidde , Zekveld Adriana A. , Saunders Gabrielle H. , Versfeld Niek J. , Lunner Thomas , Kramer Sophia E.
Published: April 2021

Objectives:

The aim of this study was to modify a speech perception in noise test to assess whether the presence of another individual (copresence), relative to being alone, affected listening performance and effort expenditure. Furthermore, this study assessed if the effect of the other individual’s presence on listening effort was influenced by the difficulty of the task and whether participants had to repeat the sentences they listened to or not.

Design:

Thirty-four young, normal-hearing participants (mean age: 24.7 years) listened to spoken Dutch sentences that were masked with a stationary noise masker and presented through a loudspeaker. The participants alternated between repeating sentences (active condition) and not repeating sentences (passive condition). They did this either alone or together with another participant in the booth. When together, participants took turns repeating sentences. The speech-in-noise test was performed adaptively at three intelligibility levels (20%, 50%, and 80% sentences correct) in a block-wise fashion. During testing, pupil size was recorded as an objective outcome measure of listening effort.

Results:

Lower speech intelligibility levels were associated with increased peak pupil dilation (PPDs) and doing the task in the presence of another individual (compared with doing it alone) significantly increased PPD. No interaction effect between intelligibility and copresence on PPD was found. The results suggested that the change of PPD between doing the task alone or together was especially apparent for people who started the experiment in the presence of another individual. Furthermore, PPD was significantly lower during passive listening, compared with active listening. Finally, it seemed that performance was unaffected by copresence.

Conclusion:

The increased PPDs during listening in the presence of another participant suggest that more effort was invested during the task. However, it seems that the additional effort did not result in a change of performance. This study showed that at least one aspect of the social context of a listening situation (in this case copresence) can affect listening effort, indicating that social context might be important to consider in future cognitive hearing research.
Wide Laminectomy, Segmental Bilateral Laminotomies, or Unilateral Hemi-Laminectomy for Lumbar Spinal Stenosis
Authors: Bouknaitir Jamal Bech , Carreon Leah Y. , Brorson Stig , Pedersen Casper Friis , Andersen Mikkel Østerheden
Published: April 2021

Study Design.

Propensity-matched retrospective study of patients prospectively enrolled in Danespine.

Objective.

The aim of this study was to report 5-year patient reported outcome in lumbar spinal stenosis (LSS) patients who underwent wide laminectomy (WL), segmental bilateral laminotomies (SBL), or unilateral hemilaminectomy (UHL) with bilateral decompression.

Summary of Background Data.

The optimal procedure for LSS remains controversial. Studies have shown no difference in short term outcomes among micro-laminectomy, hemi-laminotomies, broad laminectomy, and laminectomy with instrumented fusion.

Methods.

Patients with spinal stenosis who were enrolled in DaneSpine at two spine centers from January 2010 until May 2014 and underwent WL0, SBL, or UHL with bilateral decompression were identified. Patients completed standard questionnaires preoperatively and 1, 2, and 5 years after surgery. Patients in the three cohorts were propensity-matched using age, sex, body mass index (BMI), smoking status, number of surgical levels, American Society of Anesthesiologists (ASA) score, and patient-reported outcome measures (PROMs).

Results.

Propensity matching produced 62 cases in each group. There were no differences in PROM among the three cohorts at five years follow up. Twelve patients were re-operated at the index level. The most frequent indication of reoperation was repeat decompression after SBL. Regression analysis revealed no statistical significant associations between the incidence of reoperation and age, sex, number of operated levels, ASA score, BMI, center, smoking status, or having a dural tear at index operation.

Conclusion.

This study revealed no significant difference PROMs, reoperation rates or time to reoperation at five years follow up between SBLs, UHL, or WL in patients operated for central LSS.

Level of Evidence: 4
Magnetically Controlled Growing Rods Graduation
Authors: Lebel David Eduard , Rocos Brett , Helenius Ilkka , Sigal Amit , Struder Daniel , Yazici Muharrem , Bekmez Senol , Hasler Carol-Claudius , Pesenti Sebastien , Jouve Jen-Luc , Ovadia Dror
Published: April 2021

Study Design.

A multicenter retrospective review of consecutive series of patients.

Objective.

Long-term experience with using the magnetically controlled growing rods (MCGR) to treat patients with deformity in the growing spine to the conclusion of treatment with posterior spine fusion.

Summary of Background Data.

MCGR treatment for growing spine gained popularity with paucity of long-term follow up data. We hypothesized that final fusion might be more effective in bringing additional correction of the spine deformity after treatment with MCGR than that reported after traditional growing rods (TGR) due to less scarring and auto-fusion.

Methods.

Retrospective review of 47 patients with varied etiology, treated between 2011 and 2017 which graduated treatment were followed in five academic medical centers for average of 50 months (range, 10–88).

Results.

The initial mean coronal deformity of 69.6° (95% CI 65–74) was corrected to 40° (95% CI 36–40) immediately after the MCGR implantation but progressed to 52.8° (95% CI 46–59) prior to the final surgery (P < 0.01). Nevertheless, thoracic spine growth (T1–T12 height) improved from 187.3 mm (95% CI 179–195) following index surgery to 208.9 mm (95% CI 199–218) prior to final fusion (P < 0.01). Significant correction and spinal length were obtained at final fusion, but metallosis was a frequent observation (47%, 22/47). The average growth rate was 0.5 mm/month (95% CI 0.3–0.6). The overall complication rate within our cohort was 66% (31/47) with 45% (21/47) of unplanned returns to the operating theater. 32% (15/47) of the patients had an implant related complication. Unplanned surgery was highly correlated with thoracic kyphosis greater than 40° (OR 5.42 95% CI 1.3–23).

Conclusion.

Treatment of growing spine deformities with MCGR provides adequate control of spine deformity it is comparable to previously published data about TGR. The overall high complications rate over time and specifically implant related complications.

Level of Evidence: 4
At What Point Should the Thoracolumbar Region Be Addressed in Patients Undergoing Corrective Cervical Deformity Surgery?
Authors: Passias Peter G. , Pierce Katherine E. , Naessig Sara , Ahmad Waleed , Passfall Lara , Lafage Renaud , Lafage Virginie , Kim Han Jo , Daniels Alan , Eastlack Robert , Klineberg Eric , Line Breton , Mummaneni Praveen , Hart Robert , Burton Douglas , Bess Shay , Schwab Frank , Shaffrey Christopher , Smith Justin S. , Ames Christopher P.
Published: April 2021

Study Design.

Retrospective cohort study.

Objective.

The aim of this study was to investigate the impact of cervical to thoracolumbar ratios on poor outcomes in cervical deformity (CD) corrective surgery.

Summary of Background Data.

Consideration of distal regional and global alignment is a critical determinant of outcomes in CD surgery. For operative CD patients, it is unknown whether certain thoracolumbar parameters play a significant role in poor outcomes and whether addressing such parameters is warranted.

Methods.

Included: surgical CD patients (C2-C7 Cobb >10°, cervical lordosis [CL] >10°, C2-C7 sagittal vertical axis (cSVA) >4 cm, or chin-brow vertical angle >25°) with baseline and 1-year data. Patients were assessed for ratios of preop cervical and global parameters including: C2 Slope/T1 slope, T1 slope minus C2-C7 lordosis (TS-CL)/mismatch between pelvic incidence and lumbar lordosis (PI-LL), cSVA/sagittal vertical axis (SVA). Deformity classification ratios of cervical (Ames-ISSG) to spinopelvic (SRS-Schwab) were investigated: cSVA modifier/SVA modifier, TS-CL modifier/PI-LL modifier. Cervical to thoracic ratios included C2-C7 lordosis/T4-T12 kyphosis. Correlations assessed the relationship between ratios and poor outcomes (major complication, reoperation, distal junctional kyphosis (DJK), or failure to meet minimal clinically important difference [MCID]). Decision tree analysis through multiple iterations of multivariate regressions assessed cut-offs for ratios for acquiring suboptimal outcomes.

Results.

A total of 110 CD patients were included (61.5 years, 66% F, 28.8 kg/m2). Mean preoperative radiographic ratios calculated: C2 slope/T1 slope of 1.56, TS-CL/PI-LL of 11.1, cSVA/SVA of 5.4, CL/thoracic kyphosis (TK) of 0.26. Ames-ISSG and SRS-Schwab modifier ratios: cSVA/SVA of 0.1 and TS-CL/PI-LL of 0.35. Pearson correlations demonstrated a relationship between major complications and baseline TS-CL/PI-LL, Ames TS-CL/Schwab PI-LL modifiers, and the CL/TK ratios (P < 0.050). Reoperation had significant correlation with TS-CL/PI-LL and cSVA/SVA ratios. Postoperative DJK correlated with C2 slope/T1 slope and CL/TK ratios. Not meeting MCID for Neck Disability Index (NDI) correlated with CL/TK ratio and not meeting MCID for EQ5D correlated with Ames TS-CL/Schwab PI-LL.

Conclusion.

Consideration of cervical to global alignment is a critical determinant of outcomes in CD corrective surgery. Key ratios of cervical to global alignment correlate with suboptimal clinical outcomes. A larger cervical lordosis to TK predicted postoperative complication, DJK, and not meeting MCID for NDI.

Level of Evidence: 4
Real-World Observational Review of Andexanet Alfa Prescribing and Utilization Outcomes at a Community Teaching Hospital
Authors: Sobolewski Kristine A. , Brophy Alison , Choi Seohyun (Claudia) , Opsha Yekaterina
Published: April 2021

Objectives:

Andexanet alfa is the first approved antidote in the management of life-threatening bleeds in patients treated with Xa inhibitors. The ANNEXA-4 study was successful in reducing factor Xa levels during time of administration but lacked correlation to improved patient outcomes. Given its novel mechanism of action, U.S. boxed warning, cost of up to $58,000 per dose, and limited efficacy data compared with standard of care, hospitals are faced with a dilemma with its addition to formulary and process for ensuring optimized use. The objective of this study was to evaluate adherence to institution restriction criteria and the clinical outcomes of treatment for patients for whom andexanet alfa is requested.

Design:

Retrospective cohort study of andexanet alfa requests within a 12-month time period.

Setting:

A 600-bed community teaching hospital.

Patients:

Patients whom pharmacists received request for dispensing andexanet alfa.

Interventions:

None.

MEASUREMENTS AND MAIN RESULTS:

Quality outcomes reviewed compliance to restriction criteria. Clinical outcomes evaluated use of adjunctive blood products, ICU length of stay, hospital length of stay, and hospital mortality. Safety outcomes evaluated incidence of thrombotic events.

Andexanet alfa was requested for 16 patients from November 2018 to November 2019. It was administered in nine patients, with compliance to restriction criteria of 66.6%, average ICU length of stay 5.6 days, hospital length of stay 8.6 days, hospital mortality in 44.4%, and thrombotic events in 33.3%. Orders were rejected in seven patients with compliance to restriction criteria of 100%, ICU length of stay 3.2 days, hospital length of stay 5.5 days, hospital mortality in 14%, and thrombotic events in 14%.

Conclusions:

A greater rate of adverse effects and mortality was identified with the use of andexanet alfa compared with clinical trials. This is potentially due to its use in a more severely ill patient population and lack of adherence to restriction criteria.
In Vitro–Administered Dexamethasone Suppresses T Cell Function With Reversal by Interleukin-7 in Coronavirus Disease 2019
Authors: Mazer Monty B. , Davitt Ethan , Turnbull Isaiah R. , Caldwell Charles C. , Brakenridge Scott C. , Remy Kenneth E. , Hotchkiss Richard S.
Published: April 2021

Objectives:

Corticosteroid therapy has become standard of care therapy for hospitalized patients infected with the severe acute respiratory syndrome coronavirus-2 global pandemic-causing virus. Whereas systemic inflammation is a notably important feature in coronavirus disease 2019 pathogenesis, adaptive immune suppression and the inability to eradicate effectively the virus remain significant factors as well. We sought to evaluate the in vitro effects of dexamethasone phosphate on T cell function in peripheral blood mononuclear cells derived from patients with acute, severe, and moderate coronavirus disease 2019.

Design:

Prospective in vitro laboratory study.

Setting:

Coronavirus disease 2019-specific medical wards and ICUs at a single-center, quaternary-care academic hospital between October 1, 2020, and November 15, 2020.

Patients:

Eleven patients diagnosed with coronavirus disease 2019 admitted to either the ICU or hospital coronavirus disease 2019 unit. Three patients had received at least one dose of dexamethasone prior to enrollment.

Interventions:

Fresh whole blood was collected, and peripheral blood mononuclear cells were immediately isolated and plated onto precoated enzyme-linked immunospot plates for detection of interferon-γ production. Samples were incubated with CD3/CD28 antibodies alone and with three concentrations of dexamethasone. These conditions were also stimulated with recombinant human interleukin-7. Following overnight incubation, the plates were washed and stained for analysis using Cellular Technology Limited ImmunoSpot S6 universal analyzer (ImmunoSpot by Cellular Technology Limited, Cleveland, OH).

Measurements AND MAIN RESULTS:

Functional cytokine production was assessed by quantitation of cell spot number and total well intensity after calculation for each enzyme-linked immunospot well using the Cellular Technology Limited ImmunoSpot Version 7.0 professional software (CTL Analyzers, Shaker Heights, OH). Comparisons were made using t test and using a nonparametric analysis of variance Friedman test. The number of functional T cells producing interferon-γ and the intensity of the response decrease significantly with exposure to 1.2-µg/mL dexamethasone. About 0.12 µg/mL does not significantly affect the functional immune response on enzyme-linked immunospot. Interleukin-7 increases the overall number of activated T cells, including those exposed to dexamethasone.

Conclusions:

Further evaluation of the effect of immunomodulatory therapies is warranted in coronavirus disease 2019. A refined functional, precision medicine approach that evaluates the cellular immune function of individual patients with coronavirus disease 2019 is needed to better define which therapies could have benefit or cause harm for specific patients.
The Characterization of the Toll of Caring for Coronavirus Disease 2019 on ICU Nursing Staff
Authors: Laudanski Krzysztof , Moon Ken , Singh Amandeep , Chen Ying , Restrepo Mariana
Published: April 2021

Objectives:

Coronavirus disease 2019 pandemic exercised a significant demand on healthcare workers. We aimed to characterize the toll of caring for coronavirus disease 2019 patients by registered nurses.

Design:

An observational study of two registered nurses cohorts.

Setting:

ICUs in a large academic center.

Subjects:

Thirty-nine ICU registered nurses assigned to coronavirus disease 2019 versus noncoronavirus disease 2019 patients.

Interventions:

None.

Measurements and Main Results:

Skin temperature (t [°C]), galvanic skin stress response (GalvStress), blood pulse wave, energy expenditure (Energy [cal]), number of steps (hr–1), heart rate (min–1), and respiratory rate (min–1) were collected using biosensors during the shift. National Aeronautics and Space Administration Task Loading Index measured the subjective perception of an assignment load. Elevated skin temperatures during coronavirus disease 2019 shifts were recorded (ΔtCOVID vs tnon-COVID = +1.3 [°C]; 95% CI, 0.1–2.5). Registered nurses staffing coronavirus disease patients self-reported elevated effort (ΔEffortCOVID vs Effortnon-COVID = +28.6; 95% CI, 13.3–43.9) concomitant with higher energy expenditure (ΔEnergyCOVID vs Energynon-COVID = +21.5 [cal/s]; 95% CI, 4.2–38.7). Galvanic skin stress responses were more frequent among coronavirus disease registered nurse (ΔGalStressCOVID vs GalvStressnon-COVID = +10.7 [burst/hr]; 95% CI, 2.6–18.7) and correlated with self-reported increased mental burden (ΔTLXMentalCOVID vs ΔTLXMentalnon-COVID = +15.3; 95% CI, 1.0–29.6).

Conclusions:

There are indications that registered nurses providing care for coronavirus disease 2019 in the ICU reported increased thermal discomfort coinciding with elevated energy expenditure and a more pronounced self-perception of effort, stress, and mental demand.
Patient Adherence in an Academic Medical Center’s Low-dose Computed Tomography Screening Program
Authors: Mortman Keith D. , Devlin Joseph , Giang Brian , Mortman Ryan , Sparks Andrew D. , Napolitano Michael A.
Published: April 2021

Objectives:

Low-dose computed tomography (LDCT) screening is an important tool for reducing lung cancer mortality. This study describes a single center’s experience with LDCT and attempts to identify any barriers to compliance with standard guidelines.

Materials and Methods:

This is a retrospective review of a single university-based hospital system from 2015 to 2019. All individuals who met eligibility for lung cancer screening were entered into a database. The definition of adherence with the screening program was determined by the recommended timeline for the follow-up LDCT. Cohorts were split by adherence and demographics were compared.

Results:

A total of 203 LDCTs were performed in 121 patients who met eligibility for LDCT and had appropriate surveillance from 2015 to 2019. The average age was 64 years old. The overall adherence rate for prescribed LDCTs was 59.1%. Patients with Lung-RADS score 2 had 2.43 times higher odds of adherence relative to patients with Lung-RADS score 1 (odds ratio [OR]=2.43; 95% confidence interval [CI]: 1.23-4.83; P=0.011). African American patients had 42% lower odds of adherence relative to white patients (OR=0.58; 95% CI: 0.32-1.06; P=0.076). Patients with non–District of Columbia zip codes had 57% higher odds of adherence relative to those with District of Columbia zip codes, although this did not reach statistical significance (OR=1.57; 95% CI: 0.87-2.82; P=0.136).

Conclusions:

Despite the implementation of a multidisciplinary, academic LDCT screening program, overall adherence rate to prescribed follow-up scans was suboptimal. Socioeconomic disparities and African American race may negatively affect adherence to lung cancer screening LDCT guidelines. Patients with concerning findings on initial LDCT had a higher association of adherence to guidelines.
Impact of Integrase inhibitors and tenofovir alafenamide on weight gain in people with HIV
Authors: Lake Jordan E. , Trevillyan Janine
Published: April 2021

Purpose of review

Obesity is increasing in people with HIV (PWH). This review aims to summarise the recent evidence investigating the associations between the use of integrase inhibitors and tenofovir alafenamide (TAF) with weight gain and the mechanisms by which this may occur. Understanding the role that antiretroviral therapies play in promoting weight gain is critical in making informed treatment decisions.

Recent findings

Weight gain is common with antiretroviral therapies and can lead to significant medical complications for PWH. Antiretroviral regimens containing an integrase inhibitor in conjunction with TAF are associated with the greatest degree of weight gain. This weight gain is greatest with dolutegravir and bictegravir compared with other integrase inhibitors. Some of the measured weight gain attributed to TAF may actually reflect a loss of weight suppressant effects of tenofovir disoproxil fumarate, and thus the exact proportional contribution of TAF remains to be seen. The mechanisms by which advent of antiretroviral therapy may be promoting weight gain is still being determined but underlying genetic risks factors and gender are very important determinants of the degree of weight gained.

Integrase inhibitors and TAF contribute to weight gain in PWH. This places them at risk for potentially serious medical complications.
Heparin-Induced Bullous Hemorrhagic Dermatosis: A Report of an Exceptionally Exuberant Case and Literature Review
Authors: Cortez de Almeida Rita Fernanda , Vita Campos Clarissa , Daxbacher Egon Luiz , Jeunon Thiago
Published: April 2021

Introduction:

Heparin-induced bullous hemorrhagic dermatosis (HBHD) is an unusual cutaneous adverse reaction to heparin characterized by acute onset of hemorrhagic bullae.

Methodology:

An exuberant case of HBHD is reported, and a revision of previously reported cases indexed on PubMed is provided. Cases were tabulated to the following parameters: sex, age, type of heparin and route of administration, associated medical procedure, number of days between heparin start and onset of lesions, site of the lesions, level of blister on histopathology, inflammatory infiltrate on histopathology, direct immunofluorescence findings, heparin-related intervention, number of days to resolution of skin lesions, associated hemorrhagic event, and outcome.

Case report:

A 21-year-old woman with end-stage renal disease was receiving intravenous unfractioned heparin (UFH) during hemodialysis section for the past 3 months. Four hours after using for the first time an arteriovenous fistula punctured on her right wrist, the patient noticed the onset of vesicles and blisters on the right forearm containing citrus or serohemorrhagic exudate, which became overt hemorrhagic in 24 hours. Histopathology depicted a nonacantholytic subcorneal blister containing erythrocytes and plasma without any significant dermal inflammatory infiltrate.

Results:

Sixty cases of HBHD were included. HBHD affected predominantly men, with a male/female rate of 2.75. The age range was from 21 to 94 years, with an average of 70.8 and a median of 72 years. Nine patients used UFH, and 54 patients used low molecular weight heparins (3 patients used both). The lapse of time between the start of heparin and the onset of skin lesion varied from 6 hours to 240 days, with an average of 17.3 days and a median of 7 days. Limbs were affected in most of the cases. The level of the blister was subcorneal in 10 patients, intraepidermal in 30, subepidermal in 8, and both intraepidermal and subepidermal in 1. In 33 cases, there was no significant dermal inflammatory infiltrate. Pure lymphocytic inflammatory infiltrate was present in 10 cases. Eosinophils were found within the dermal inflammatory infiltrate in 2 cases, neutrophils in 2, and a mixture of eosinophils and neutrophils in other 2. Direct immunofluorescence was performed in 18 cases, all of them with negative results.

Discussion:

We hypothesize that mechanical trauma, skin fragility, and the anticoagulation effect of heparin might contribute concomitantly to the development of the lesions and speculate that subepidermal blisters in HBHD could be formed by rupture of the floor of a former intraepidermal blister.
Eruptive Xanthoma With Dermal Mucin Deposition
Authors: Kim So Min , Lee Heera , Kim You Chan
Published: April 2021

Xanthomas present clinically as eruptive, tuberoeruptive, tuberous, tendinous, or planar forms. Among these, eruptive xanthoma (EX) is characterized by sudden development of multiple, red-to-yellow papules, each less than 5 mm in diameter, on the extensor surface of the extremities and the buttock area. EX is often associated with severe hypertriglyceridemia, underlying diabetes, obesity, or excessive alcohol intake. Histologically EX is characterized by foamy cells, which are lipid-laden macrophages surrounded by lymphoid cells, histiocytes, and neutrophils; however, mucin deposition is not a typical feature. Herein, we report a rare case of xanthoma with diffuse, abundant mucin deposition.
Rate of Immunohistochemistry Utilization in the Diagnosis of Cutaneous Melanocytic Lesions
Authors: Chen Tony C. , Hitchcock Michael G.
Published: April 2021

Melanocytic lesions represent a large portion of the workload in many laboratories. Although many melanocytic nevi can be confidently diagnosed based on routine hematoxylin and eosin light microscopy, ancillary testing is often warranted. Various immunohistochemical (IHC) stains are routinely used in the diagnosis of melanocytic lesions. Because melanocytic lesions are frequently encountered in skin specimens, the use of IHC is likely to represent a significant area of resource utilization in dermatopathology laboratories. Our study investigates the rate of IHC utilization in the diagnosis of melanocytic lesions in a high-volume, government-funded, not-for-profit laboratory. Of the 1230 cases of melanocytic lesions investigated, including benign as well as malignant entities, 300 cases involved the utilization of IHC. IHC was used in a larger percentage of melanomas than nevi and in a larger percentage of melanoma in situ cases than invasive melanomas. SOX10 was overwhelmingly the most frequently used IHC.
Focal Synovial Inflammation Versus Enthesitis Theory in Distal Psoriatic Arthritis: A Pioneer Histopathologic Study
Authors: Perrin Christophe
Published: April 2021

The aim of this analysis was to re-examine the classical concept of distal interphalangeal joint (DIP) psoriatic arthritis (PsA) as an entheseal-driven disease. Two cadaveric fingers with severe psoriatic arthritis were analyzed. Our results demonstrate that inflammation of DIP PsA is multifocal without interconnection between entheses and articular cartilage of the DIP. We found a clear association between synovitis and focal loss of articular cartilage at the head of the intermediate phalanx. By contrast, the articular cartilage adjacent to the zone of severe enthesitis did not show notable damage. Fibrocartilaginous destructions of enthesis were characterized by either a multifocal lymphocytic inflammation, accompanied by osteoclastic resorption, beginning on the interface between the uncalcified and calcified fibrocartilage and then extending into the bone or a subchondral bone inflammation which insidiously destroyed first the bone and then the fibrocartilage. Some sections well showed an inflammation either mild or prominent starting at the level of vascular foramina of flexor enthesis, with secondary invading into the interface between bone and enthesis. The different anatomic sites examined showed a slight predominance of CD8+ T cells over CD4+ T cells: 52% up to 63% for CD8+ T cells vs. to 36% up to 48% for CD4+ T cells. Sparse interspersed CD1a+cells and PS100+cells were also seen with a predominance of PS100+ cells on CD1a+ cells. CD20+ B cells, plasmocytes, neutrophils, and mastocytes were absent or rare. CD123 positive cells were not observed. In DIP PsA, 3 findings predominate: (1) cartilage invasion by the thin pannus offers a more rational explanation for the focal joint destruction than does inflammation of the enthesis which is independent from articular cartilage, (2) the thick ventral plate and to a lesser extend the thin dorsal plate constitute a barrier between the inflamed entheses and the articular cartilage, and (3) an unusual form of minute vascular foramen contributes to the early stage of enthesitis. This small study suggests that DIP PsA is a complex disease. It affects anatomical micro sites which, although close, are in fact relatively independent of each other. Further studies are needed to test this hypothesis.
Recurrence Rates Following Reconstruction Strategies After Wide Excision of Hidradenitis Suppurativa: A Systematic Review and Meta-analysis
Authors: Ovadja Zachri N. , Zugaj Mislav , Jacobs Wilco , van der Horst Chantal M.A.M. , Lapid Oren
Published: April 2021

BACKGROUND

Wide excision (WE) is generally considered to be the most common treatment for recurrent hidradenitis suppurativa. When performed, excision is followed by decisions regarding best options for management of the surgical defect. Different reconstructive strategies (RSs) have been used, with varying rates of recurrence.

OBJECTIVE

To provide an up-to-date systematic review of the complete literature for different RS after WE and their recurrence rates.

METHODS

A systematic literature search of the complete available literature and a meta-analysis of proportions were performed on the included studies.

RESULTS

Of a total of 1,813 retrieved articles, 79 were included in the analysis. Most were retrospective analyses, with only one randomized controlled trial (RCT) and 7 prospective analyses. The RS described were divided into primary closure (PC), secondary intention healing (SIH), skin graft (SG), and fasciocutaneous flaps (FCF). The average estimated recurrence for PC was 22.0% (95% confidence interval [CI], 8.0%–40.0%), for SIH 11.0% (95% CI, 5.0%–20.0%), for SG 2.0% (95% CI, 0.0%–5.0%), and for FCF 2.0% (95% CI, 1.0%–5.0%) (p < .001). Hidradenitis suppurativa below the umbilicus was significantly associated with overall recurrence (p = .006). Quality of evidence was poor, and the reporting of results was mostly heterogeneous.

CONCLUSION

After WE, PC has the highest recurrence rates, whereas SG and FCF have the lowest rates. There is a need for more RCTs and guidelines, to be able to report uniformly on treatment outcomes.
A Histopathologic Scoring System for Perineural Invasion Correlates With Adverse Outcomes in Patients With Cutaneous Squamous Cell Carcinoma
Authors: Totonchy Mariam B. , McNiff Jennifer M. , Suozzi Kathleen C. , Leffell David J. , Christensen Sean R.
Published: April 2021

BACKGROUND

Perineural invasion (PNI) is a known risk factor for recurrence, metastasis, and death in cutaneous squamous cell carcinoma (cSCC). Current staging systems include PNI, but none define its extent or severity.

OBJECTIVE

To identify histopathologic features of cSCC with PNI that may be associated with adverse outcomes.

MATERIALS AND METHODS

This is a retrospective cohort study that included 45 patients with cSCC and PNI treated with surgical excision. Histopathologic slides were analyzed for 5 features of PNI: largest affected nerve diameter, number of nerves affected, depth of nerve involvement, intra- versus extratumoral PNI, and focal versus circumferential PNI.

RESULTS

The median largest affected nerve diameter was 0.13 mm, and the median number of nerve structures involved was 4. After a median follow-up time of 24 months, 6 patients developed adverse outcomes, including 2 local recurrences, 4 metastases, and 2 tumor-related deaths. Univariate logistic regression analysis revealed that nerve diameter and number of affected nerves were significantly associated with adverse outcome. A composite PNI score, calculated from 5 histopathologic features, was the strongest predictor of adverse outcome (p = .020).

CONCLUSION

Histopathologic features of PNI can be quantified with a composite PNI score that is significantly associated with adverse outcomes in cSCC.
The mediation effect of placental weight change in the association between prenatal exposure to selenium and birth weight
Authors: Wang Jiaqi , Qian Rui , Wang Yiding , Dong Moran , Liu Xin , Zhou He , Ye Yufeng , Chen Guimin , Chen Dengzhou , Yuan Lixia , Xiao Jianpeng , He Guanhao , Hu Jianxiong , Zeng Weilin , Rong Zuhua , Zhang Qianqian , Zhou Mengya , Jin Juan , Fan Jingjie , Sun Jiufeng , Ma Wenjun , Zhang Bo , Liu Tao
Published: April 2021

Background:

Selenium (Se) is an essential element and also toxic at an excessive level for human body. However, few studies have investigated adverse effects of Se exposure on birth weight and placental weight.

Methods:

All participants were selected from the Prenatal Environment and Offspring Health cohort conducted in 2016 in Guangzhou, China. Se in each participant was measured by inductively coupled plasma mass spectrometry in their urine samples. The urinary Se concentrations were corrected by creatinine and transformed by natural logarithm (ln-Se). Multiple-linear regression models were applied to estimate the associations among Se exposure levels, placenta weight, and birth weight.

Results:

A total of 2758 mother-newborn pairs were included in this study. Each interquartile range (0.53 μg/g creatinine) increment in urine ln-Se concentration during the first trimester was associated with a mean 21.7 g (95% CI = −41.3g to −2.1g) decrease in birth weight and 3.6g (95% CI = −6.3g to −0.9g) decrease in placental weight. Compared with the lowest quartile (Q1) of ln-Se concentrations during the first trimester, significantly lower birth weight was found in the highest quartile (Q4) (β = −45.7g; 95% CI = −90.7g to −0.7g). Similar dose-response associations with birthweight and placental weight were found for Se exposure during the third trimester. Mediation analyses showed that 44.2% and 18.2% of the effects of Se exposure in first and third trimester on birth weight were mediated by decreased placental weight, respectively.

Conclusion:

Maternal Se exposure during pregnancy was negatively associated with birth weight, the reduction of placental weight may partially mediate the association of prenatal Se exposure with birth weight.
The impact of image resolution on power, bias, and confounding
Authors: McIsaac Michael A. , Sanders Eric , Kuester Theres , Aronson Kristan J. , Kyba Christopher C. M.
Published: April 2021

Background:

Studies of the impact of environmental pollutants on health outcomes can be compromised by mismeasured exposures or unmeasured confounding with other environmental exposures. Both problems can be exacerbated by measuring exposure from data sources with low spatial resolution. Artificial light at night, for example, is often estimated from low-resolution satellite images, which may result in substantial measurement error and increased correlation with air or noise pollution.

Methods:

Light at night exposure was considered in simulated epidemiologic studies in Vancouver, British Columbia. First, we assessed statistical power and bias for hypothetical studies that replaced true light exposure with estimates from sources with low resolution. Next, health status was simulated based on pollutants other than light exposure, and we assessed the frequency with which studies might incorrectly attribute negative health impacts to light exposure as a result of unmeasured confounding by the other environmental exposures.

Results:

When light was simulated to be the causal agent, studies relying on low-resolution data suffered from lower statistical power and biased estimates. Additionally, correlations between light and other pollutants increased as the spatial resolution of the light exposure map decreased, so studies estimating light exposure from images with lower spatial resolution were more prone to confounding.

Conclusions:

Studies estimating exposure to pollutants from data with lower spatial resolution are prone to increased bias, increased confounding, and reduced power. Studies examining effects of light at night should avoid using exposure estimates based on low-resolution maps, and should consider potential confounding with other environmental pollutants.
Urgent Need of Continuing Medical Education: The Key for Patient Awareness of Labor Epidural Analgesia – A Survey of Chinese Perinatal Care Providers
Authors: Zhao Peishan , Hu Ling-Qun , Liu Chunyuan , Li Huiling , Huang Anna , Yang Shuwei , Cai Zhenyu
Published: April 2021

Objective:

This survey was designed to understand the misconceptions about labor epidurals.

Methods:

This voluntary and anonymous online survey on wenjuan.com was conducted from September 1st, 2015 to January 1st, 2016 via mainly WeChat groups dedicated to perinatal healthcare providers in China. The questionnaire included items inquiring the knowledge and opinions about labor epidural analgesia related to maternal complications, baby safety, and effect on laboring. Incomplete surveys were excluded from the data analysis. The data was presented as percentages and a Chi-square test or Fisher's exact test, as appreciate, was used to quantitatively compare the results.

Results:

A total of 1412 respondents completed surveys with 42.9% (606/1412) of them being anesthesiologists, 35.1% (495/1412) being obstetricians, 11.8% (167/1412) being midwives, 3.7% (52/1412) being labor and delivery nurses, and 6.5% (92/1412) being hospital administrators and unspecified. The study revealed a lack of knowledge in labor pain control. Although 82.4% (1164/1412) of respondents were familiar with labor epidural analgesia, 8.9% (126/1412) did not know how it works, and 1.1% (15/1412) never heard it in a multiple-choice question. The three main groups (anesthesiologists, obstetricians, and midwives/labor and delivery nurses) were chosen for comparisons. Opinions among these three groups concerning five questions in the three main concerns were evaluated using a statistical significance of P < 0.05.

Conclusion:

The results in our survey indicated an urgent need of continuing medical education to multidisciplinary specialties to improve evidence-based medical practices as these misconceptions have existed for over 10 years in the medical professionals. Lack of public awareness fueled by misconceptions related to labor epidural analgesia may be associated with a lack of professional knowledge. Correct knowledge in professionals needs to be disseminated to the public in order to dispel possible misconceptions and rumors about labor epidural analgesia. This would not only enhance patient understanding of their care but also improve maternal, fetal, and neonatal outcomes.