bluuebunny/crossref_metadata_2025 huggingface dataset:
Nietzschean Monism? A Pandispositionalist Proposal
Authors: Riccardi Mattia
Published: October 2020

I argue that Nietzsche puts forward a pandispositionalist view that can be seen as the conjunction of two basic claims: that powers are the basic constituents of reality, on the one hand, and that the only properties things possess are relational qua dispositional, on the other hand. As I believe that such a view is, at least in part, motivated by his rejection of Kant’s notion of things in themselves, I start by sketching the metaphysics of Kant’s transcendental idealism (section 2) and by presenting Nietzsche’s critical reaction to it (section 3). After that, I start to work out Nietzsche’s pandispositionalist view by considering first the case of physical reality (section 3) and second that of psychological reality (section 5). I then argue that in both cases that view does not conflict with Nietzsche’s naturalism (section 6). In the last part of the paper I explore how his notion of will to power fits into such a pandispositionalist picture. Here, I shall argue, some serious tension does arise, for the claim that Nietzsche sometimes makes to the effect that the will to power is a fundamental physical force seems to clash with central aspects of his mature thought (section 7). However, whereas he repeatedly entertains that claim in his unpublished notes, it is far from clear that he ever meant to endorse it in his published work. Thus, I conclude that the available textual evidence only justifies attributing to Nietzsche the kind of pandispositionalist view spelled out in the first sections of the present paper, and not also the further claim that the will to power is a fundamental physical force (section 8).
The role of VEGF receptor inhibitors in preventing cerebral radiation necrosis: a retrospective cohort study
Authors: Alnahhas Iyad , Rayi Appaji , Palmer Joshua D , Raval Raju , Folefac Edmund , Ong Shirley , Giglio Pierre , Puduvalli Vinay
Published: October 2020

Background

Radiation necrosis (RN) is a potential complication after radiation therapy for brain tumors. It is hypothesized that VEGF plays an important role in the pathophysiology of RN. Bevacizumab, a monoclonal antibody against VEGF-A, is often successful in the management of RN. The objective of this study is to assess whether VEGF receptor (VEGFR) inhibitors, a group of oral tyrosine kinase inhibitors (TKIs), can prevent or reverse RN.

Methods

We retrospectively studied a cohort of 102 patients with renal cell carcinoma and brain metastases seen at The Ohio State University James Cancer Center between January 1, 2011 and April 30, 2019. We identified those who developed RN and analyzed the temporal relationship between the use of VEGFR TKIs and the development of RN.

Results

The cumulative incidence of RN is 13.7% after radiation treatments that included LINAC-based stereotactic radiosurgery, fractionated stereotactic radiotherapy, or Gamma Knife radiosurgery. There was no statistically significant difference in the cumulative incidence of RN between patients taking TKIs and patients who were off TKIs (9.9% and 11.5% respectively, P = .741). The median time to development of RN was only numerically shorter in patients taking TKIs (151 vs 315 days, P = .315). One patient developed RN after stopping cabozantinib. Eight patients developed RN while on cabozantinib, pazopanib, or sunitinib. One patient was started on axitinib during active RN without significant improvement subsequently.

Conclusions

VEGFR TKIs do not consistently prevent RN. The therapeutic effects of VEGFR TKIs against RN warrant further research.
Field Evaluation of Cholkit Rapid Diagnostic Test forVibrio Cholerae O1During a Cholera Outbreak in Malawi, 2018
Authors: Chibwe Innocent , Kasambara Watipaso , Kagoli Mathews , Milala Harry , Gondwe Charity , Azman Andrew S
Published: October 2020

Rapid diagnostic tests (RDTs) for cholera are an important emerging tool for surveillance, yet the currently available tests have several limitations. We assess the performance of a new RDT, Cholkit, during a cholera outbreak in Malawi compared with culture and find a sensitivity of 93.0% (95% CI, 83.0%–98.1%) and a specificity of 95.7% (95% CI, 78.1%–100.0%).
Associations Between Relative Viral Load at Diagnosis and Influenza A Symptoms and Recovery
Authors: McKay Brian , Ebell Mark , Billings Wesley Zane , Dale Ariella Perry , Shen Ye , Handel Andreas
Published: October 2020

Background

Rapid point-of-care polymerase chain reaction (PCR) diagnostic tests generally provide a qualitative result of positive or negative only. Additional information about the relative viral load could be calculated. Such quantitative information might be useful for making treatment decisions.

Methods

We enrolled students at a university health center who presented with cough and 1 additional flu-like symptom from December 2016 to February 2017. Data were collected before, during, and 5 days after the clinic visit. All those enrolled in the study received a point-of-care PCR test (cobas Liat). For those patients that tested positive for influenza A, we investigated correlations between the relative viral load and measures of disease severity and recovery.

Results

One hundred thirty-five students tested positive for influenza A. We found a positive correlation between viral load and body temperature. Time since symptom onset seemed to have a negative correlation but was not statistically significant. We did not find any correlations between viral load and overall symptom severity or outcomes related to recovery.

Conclusions

Although we found a correlation between relative viral load and body temperature, for our study population of young, overall healthy adults, we did not find that relative viral load provided additional information that could help in determining treatment and disease outcomes. It could be that viral load does provide useful additional information for other groups of patients, such as young children or older adults. Further studies on those populations are warranted.
Plant and Soil Drivers of Whole-Plant Microbiomes: Variation in Switchgrass Fungi from Coastal to Mountain Sites
Authors: Lee Marissa R. , Hawkes Christine V.
Published: October 2020

Plant-associated microbial diversity is regulated by dispersal from local and regional species pools, as well as filtering by the environment and plant host. However, few studies have simultaneously examined microbial community variation in multiple plant-associated habitats across multiple sites; thus, it is unclear what scales and filters are most important in shaping whole-plant microbiome diversity. To address this, we characterized fungal communities associated with switchgrass (Panicum virgatum L.) leaves, roots, and soils within and across 14 stands spanning mountain to coastal ecoregions of North Carolina. Niche differences at small scales (i.e., less than half a kilometer) best explained variation in fungal communities. However, the specific environmental drivers of fungal community composition differed for leaves, roots, and soils. Leaf and root fungi were both affected by plant height, whereas soil fungi were controlled by stand age. Different soil properties were important for fungi in all plant-associated habitats: K, P, and pH for leaves; clay, Mn, and pH for roots; and clay, dissolved organic carbon, total inorganic N, and Cu for soils. Climate and spatial variables were not significant, further supporting the key role of plant and soil properties. Advances such as these will help us explain, predict, and manipulate microbial assemblages that support plant growth in managed and natural systems.
Complete Genome Sequence Resource for the Necrotrophic Plant-Pathogenic Bacterium Dickeya dianthicola 67-19 Isolated From New Guinea Impatiens
Authors: Liu Yingyu , Helmann Tyler C. , Stodghill Paul , Filiatrault Melanie J.
Published: October 2020

New Guinea impatiens (NGI, Impatiens hawkeri) are popular bedding plants that can be affected by a number of pathogens. Using 16S rDNA sequencing and genus-specific PCR, we identified the first Dickeya dianthicola strain isolated from NGI presented with blackleg symptoms, herein designated as D. dianthicola 67-19. Here, we report a high-quality complete and annotated genome sequence of D. dianthicola 67-19. The 4,851,809 bp genome was assembled with Nanopore reads and polished with Illumina reads, yielding 422× and 105× coverage, respectively. This closed genome provides a resource for future research on comparative genomics and biology of D. dianthicola, which could translate to improved detection and disease management.
Surgery for Degenerative Cervical Myelopathy
Authors: Gembruch Oliver , Jabbarli Ramazan , Rashidi Ali , Chihi Mehdi , Hetze Susann , Barthel Lennart , Toplak Adrian , El Hindy Nicolai , Sure Ulrich , Dammann Philipp , Özkan Neriman
Published: October 2020

Study Design.

Retrospective study (data analysis).

Objective.

The purpose of this study was to assess the role of different factors on postoperative outcome of patients with degenerative cervical myelopathy (DCM).

Summary of Background Data.

Ongoing degenerative changes of DCM lead to progressive neurological deficits. The optimal timing of surgical treatment is still unclear, especially in patients with mild DCM.

Methods.

Patients with DCM treated in our clinic between 2007 and 2016 were retrospectively analyzed. Pre- and postoperative neurological function was assessed by the modified Japanese Orthopaedic Association Score (mJOA Score) at different stages. The minimum clinically important difference (MCID) was used to evaluate the improvement after surgery. The comorbidities were recorded using the Charlson Comorbidity Index (CCI). Possible associations between age, sex, CCI, preoperative symptoms duration, high signal intensity (SI) on T2-weighted magnetic resonance imaging (MRI) with mJOA Score and MCID were analyzed using univariate analysis and multivariate regression models. Additionally, subgroup analysis was performed according to the severity of DCM (mild: mJOA Score ≥15 points; moderate: mJOA Score of 12–14 points; and severe: mJOA Score <12 points).

Results.

The mean age of the final cohort (n = 411) was 62.6 years (range: 31–96 years), 36.0% were females. High SI on T2-weighted MRI was detected in 60.3% of the cases. In the multivariate analysis, patients’ age (P = 0.005), higher CCI (P = 0.001), and presence of high SI on T2-weighted MRI (P = 0.0005) were associated independently with lower pre- and postoperative mJOA Score and postoperative MCID. Subgroup analysis revealed age and high SI on T2-weighted MRI as predictors of pre- and postoperative mJOA. However, symptom duration did not influence neurological outcome according to the severity of DCM.

Conclusion.

Surgery for DCM leads to significant functional improvement. However, better outcome was observed in younger individuals with lower CCI and absence of radiographic myelopathy signs. Therefore, DCM surgery, particularly before occurrence of high SI on MRI, seems to be essential for postoperative functional improvement regardless the above-mentioned confounders.

Level of Evidence: 3
Cervical Spinal Fusion in Adult Patients With Rheumatoid Arthritis
Authors: Fields Michael W. , Lee Nathan J. , Hong Daniel Y. , Para Ashok , Boddapati Venkat , Mathew Justin , Kim Jun S. , Lombardi Joseph , Lehman Ronald A. , Riew K. Daniel
Published: October 2020

Study Design.

Retrospective cohort study.

Objective.

The purpose of this study was to utilize the National Readmission Database to determine the national estimates of complication and 90-day readmission rates associated with cervical spinal fusion in adult patients with rheumatoid arthritis (RA).

Summary of Background.

RA patients who undergo cervical spine surgery are known to be at high risk for readmissions, which are costly and may not be reimbursed by Medicare.

Methods.

The National Readmission Database was queried for adults (>18 years) diagnosed with RA undergoing cervical spine fusion. Patient, operative, and hospital factors were assessed in bivariate analyses. Independent risk factors for readmissions were identified using stepwise multivariate logistic regression.

Results.

From 2013 to 2014, a total of 5597 RA patients (average age: 61.5 ± 11.2 years, 70.9% female) underwent cervical spine fusion. A total of 691 (12.3%) patients were readmitted within 90 days (Table 1). Index inpatient complications included dysphagia (readmitted: 7.9% vs. non-readmitted: 5.1%; P = 0.003), urinary tract infection (UTI) (8.8% vs. 3.7%; P < 0.001), respiratory-related complications (7.6% vs. 3.4%; P < 0.001), and implant-related complications (5.4% vs. 2.7%; P < 0.001). Multivariate logistic regression demonstrated the following as the strongest independent predictors for 90-day readmission: intraoperative bleeding (odds ratio [OR]: 3.6, P = 0.001), inpatient Deep Vein Thrombosis (DVT) (OR 4.1, P = 0.004), and patient discharge against medical advice (OR 33.5, P = 0.001).

Conclusion.

Readmission rates for RA patients undergoing cervical spine surgery are high and most often due to postoperative infection (septicemia, UTI, pneumonia, wound). Potential modifiable factors which may improve outcomes include minimizing intraoperative blood loses, postoperative DVT prophylaxis, and discharge disposition.

Level of Evidence: 3
Long-term Radiographic Outcome of Occipitocervical Fixation
Authors: Shimizu Takayoshi , Fujibayashi Shunsuke , Otsuki Bungo , Takemoto Mitsuru , Murata Koichi , Matsuda Shuichi
Published: October 2020

Study Design.

Retrospective case series

Objective.

The aim of this study was to investigate the long-term radiographic outcome of patients who underwent occipitocervical fixation (OCF) using a modern screw/rod system.

Summary of Background Data.

Few studies have reported fusion rates and radiographic alignment changes in unfused subaxial segments after OCF at a long-term follow-up.

Methods.

We retrospectively reviewed 22 patients who underwent OCF with a modern screw-based construct. The patients satisfied the minimum 2-year radiographic follow-up. Baseline demographics and the following pre- and postoperative sagittal alignment parameters were investigated. McGregor slope, O-C2 angle (OC2A), and C2-7 Cobb angle (CL). We grouped patients into those whose OC2A increased postoperatively (OC2A-increase group) and those whose OC2A decreased postoperatively (OC2A-decrease group). The postoperative sagittal alignment change was compared between the 2 groups at the final follow-up. The perioperative complications as well as fusion status based on computed tomography (CT) were investigated.

Results.

The average follow-up period was 89.7 months. The lowest instrumented vertebra was at C2 (63.6%), C3 (18.1%), or C4 (18.1%). The fusion rate at the final follow-up was 77.2%. Postoperative dysphasia occurred in two patients (16.6%) in the OC2A-decrease group, whereas distal junctional kyphosis was observed in two patients (20.0%) in the OC2A-increase group. The OC2A-increase group demonstrated a mean 4.8° decrease in CL as a compensation for the 5.1° increase in OC2A. In contrast, the OC2A-decrease group showed a mean 9.2° increase in CL as a compensation for the 6.3° decrease in OC2A.

Conclusion.

The CT-confirmed fusion rate of OCF was 77.2% over an average 89.7-month follow-up. Compensatory sagittal alignment change can occur in the unfused subaxial segments in conjunction with the alignment change in the instrumented OC segments, whereas the horizontal gaze was maintained. Strong consideration for the intraoperative measurement of the OC2A should be given during OCF to minimize both early and long-term complications.

Level of Evidence: 4
Clinical Pharmacists: An Invaluable Part of the Coronavirus Disease 2019 Frontline Response
Authors: Ferguson Nadia C. , Quinn Nicholas J. , Khalique Saira , Sinnett Mark , Eisen Lewis , Goriacko Pavel
Published: October 2020

Although coronavirus disease 2019 was first identified in December 2019, it rapidly spread and became a global pandemic. The number of patients infected with the novel coronavirus (severe acute respiratory syndrome coronavirus 2) rose rapidly in New York State, placing great stress on healthcare systems. The traditional roles and practices of healthcare providers were dramatically redefined to meet the demand to care for the large number of ill patients. While literature reports on the experiences of many frontline staff, there is a scarcity of reports on the role of clinical pharmacists during this crisis. We report the role of critical care clinical pharmacists at a large academic medical center in New York City during this pandemic. Effective crisis management required clinical pharmacists to employ a wide array of skills and knowledge. Areas included clinical expertise, education, data analysis, health informatics infrastructure, and inventory management in times of surging medication use and manufacturer shortages. Clinical pharmacists fulfilled an essential service during the coronavirus pandemic by working to ensure the best possible outcomes for the patients they served on the frontline.
Impact of CYP2D6, CYP3A5, and ABCB1 Polymorphisms on Plasma Concentrations of Donepezil and Its Metabolite in Patients With Alzheimer Disease
Authors: Kagawa Yoshiyuki , Yamamoto Yoshiaki , Ueno Ayami , Maeda Toshio , Obi Tomokazu
Published: October 2020

Background:

Donepezil is one of the most commonly prescribed drugs for the treatment of Alzheimer disease. It is predominantly metabolized through CYP2D6 and to a lesser extent by CYP3A4/5. There are conflicting reports regarding the influence of CYP2D6, CYP3A5, and ABCB1 polymorphisms on the plasma concentration of donepezil. This study investigated the influence of these polymorphisms and sex on the plasma concentrations of donepezil and its active metabolite, 6-O-desmethyl donepezil (6ODD), in 47 patients with Alzheimer disease.

Methods:

Plasma donepezil and 6ODD concentrations were measured using liquid chromatography tandem mass spectrometry. Sex, the concomitant use of psychotropics, and CYP2D6, CYP3A5, and ABCB1 polymorphisms were analyzed as possible influencers.

Results:

The mean plasma concentrations of donepezil and 6ODD were well correlated (R2 = 0.418). The mean plasma concentration ratio of donepezil to 6ODD (metabolic ratio) was significantly lower in intermediate metabolizers of CYP2D6 than in extensive metabolizers. The metabolic ratio in patients receiving psychotropics was significantly lower than in those not receiving psychotropics. Among intermediate metabolizers, patients positive for CYP3A5 *3/*3 showed a significant increase in plasma mean 6ODD concentrations when compared with those who did not express this gene (CYP3A5 *1/*1 or *1/*3).

Conclusions:

Results indicate that the mean plasma concentration ratio of donepezil to 6ODD is associated with CYP2D6 polymorphism and the concomitant use of psychotropics in patients with Alzheimer disease. In intermediate metabolizers, CYP3A5 may play a significant role in the metabolism of donepezil.
Medical Cost of Workers’ Compensation Claims Related to Patient Handling and Mobility Tasks Within Skilled Nursing Facilities, Continuing Care Retirement Communities and Assisted Living Facilities
Authors: Pieretti Luis F. , Sylvester Robert A. , Siegfried Karl V.
Published: October 2020

Objective:

Evaluate the medical costs related to patient handling & mobility (PH&M) claims.

Methods:

Closed medical only and indemnity workers’ compensation claims were utilized for this exploratory study. In addition to the PH&M tasks, the claimants’ gender, age, tenure, and the claim lag time were also analyzed.

Results:

Generalized linear models indicated that variables related to tasks, claims’ number of open days and age of the claimants had meaningful effects on the adjusted medical costs for medical only claims. For indemnity claims, the number of open days of claims, age and tenure had meaningful effects. Gender had meaningful effects only for indemnity claims when classifying the claims by patient handling tasks versus non-patient handling tasks.

Conclusions:

Results showed that factors, other than the type of injury; meaningfully influenced the adjusted medical costs of indemnity claims.
PROBE Study: A Sentinel Surveillance System to Monitor Exposure of Belgian Employees to Hazardous Chemicals
Authors: Pauwels Sara , Swinnen Celien , Temmerman Anne-Marie , Ronsmans Steven , Rusu Dorina , De Schryver Antoon , Braeckman Lutgart , Godderis Lode
Published: October 2020

Objective:

To test the feasibility of collecting reliable and representative data on exposure of Belgian employees to a selection of hazardous chemicals by using a sentinel surveillance method.

Method:

In PROBE (Hazardous chemical Products Register for Occupational use in Belgium), 47 occupational physicians were recruited as a sentinel network. Employees answered a web-based survey assessing their past week exposure to 22 chemicals.

Results:

47% employees were exposed to at least one chemical. The most frequently reported exposures was to diesel exhaust (14%). The exposed employees were mostly older men, with most exposed during production and manufacturing, and working in smaller companies. For diesel exhaust, wood dust, and crystalline silica, 54%, 32%, and 20% of the exposed employees, did not use collective/personal protective equipment.

Conclusion:

Sentinel surveillance is a feasible method for obtaining high-quality data on the exposure of Belgian employees to hazardous chemicals.
Implementing Patient-Centered Trauma-Informed Care for the Perinatal Nurse
Authors: Kuzma Elizabeth K. , Pardee Michelle , Morgan Anna
Published: October 2020

Adverse childhood experiences and trauma significantly impact physical and mental health. Increased maternal perinatal depression/anxiety, preterm labor, and low birth weight, as well as infant morbidity and mortality, are some examples of the impact of trauma on perinatal health. Trauma-informed care begins with knowledge about trauma, the ability to recognize signs of a trauma response, responding to patients effectively, and resisting retraumatization. As holistic providers, perinatal nurses can create safe care environments, establish collaborative patient relationships based on trust, demonstrate compassion, offer patients options when possible to support patient autonomy, and provide resources for trauma survivors. This can prevent or reduce the negative impact of trauma and improve the health and well-being of infants, mothers, and future generations. This clinical article outlines key strategies for implementation of patient-centered trauma-informed perinatal nursing care.
Newborn Screening Knowledge and Attitudes Among Midwives and Out-of-Hospital-Birth Parents
Authors: Coupal Elena , Hart Kim , Wong Bob , Rothwell Erin
Published: October 2020

Midwifery and nursing are collaborative partners in both education and practice. Understanding needs and barriers to clinical services such as newborn screening is essential. This study examined knowledge and attitudes of midwives and out-of-hospital-birth parents about newborn blood spot screening (NBS). Descriptive and cross-sectional surveys were distributed to midwives and out-of-hospital-birth parents from birth center registries and the Utah Health Department of Vital Records. Seventeen midwife surveys (response rate: 17%) and 113 parent surveys (response rate: 31%) were returned. Most midwives and out-of-hospital-birth parents reported satisfactory knowledge scores about NBS. Only 5% of parents (n = 6) did not participate in NBS. Most midwives reported that NBS is important and encouraged patients to consider undergoing NBS. Some concerns included the lack of education for both midwives and out-of-hospital patients and the trauma and accuracy of the heel prick soon after birth. Both midwives and out-of-hospital-birth parents expressed a need for improved NBS education. Additional studies are needed to ascertain whether this trend is seen with similar populations throughout the United States, to further elucidate the factors that drive NBS nonparticipation, and to develop educational resources for midwives and their patients.
Decision Making in Patients With Concomitant Otosclerosis and Superior Semicircular Canal Dehiscence: A Systematic Review of the Literature
Authors: Fernandez Ignacio J. , Molinari Giulia , Presutti Livio
Published: October 2020

Objective:

Concomitant otosclerosis (OTS) and superior semicircular canal dehiscence (SSCD) is a rare, but difficult-to-identify and treat diagnosis. A systematic review of the literature was performed to analyze the diagnostic and therapeutic approaches of concurrent OTS and SSCD cases and to identify possible factors that may help in predicting the surgical outcome.

Data Sources:

PubMed, Scopus, Medscape, Ovid databases.

Study Selection:

Studies showing diagnosis of OTS documented by audiometric test with or without associated radiological signs (computed tomography), and concomitant diagnosis of SSCD, documented at least by high-resolution computed tomography (and possibly supported by neurophysiological testing) were included. Both surgically treated and untreated patients were considered for data analysis.

Data Extraction:

The general characteristics of each study were recorded, when available. Clinical, audiological, vestibular testing, surgical, and radiological data were extracted from the published case reports and series, and recorded on a database. For each case, the diagnostic steps that confirmed OTS and concomitant SSCD in the same ear were extracted.

Data Synthesis:

Twelve studies were included in the review and 18 cases affected simultaneously by the 2 conditions were extracted and analyzed. Seven of 12 ears (58.3%) undergoing stapes surgery experienced a hearing improvement. In four (33.3%) cases, vestibular symptoms (with or without associated acoustic symptoms) of SSCD were unmasked or worsened by stapes surgery.

Conclusions:

A reliable preoperative diagnosis of the two concomitant conditions is possible with a proper interpretation of clinical signs, audiometric, and vestibular testing, in association with the radiologic assessment. Despite that the length and the location of the dehiscence may guide the surgical decision, definitive conclusions regarding the appropriate indications for surgical treatment cannot be drawn due to the limited number of cases with adequate data reported in the literature.
Carbon Dioxide Elimination During Veno-Venous Extracorporeal Membrane Oxygenation Weaning: A Pilot Study
Authors: Belliato Mirko , Cremascoli Luca , Epis Francesco , Ferrari Fiorenza , Quattrone Maria G. , Malfertheiner Maximilian V. , Broman Lars M. , Aliberti Anna , Taccone Fabio S. , Iotti Giorgio A. , Lorusso Roberto
Published: October 2020

Veno-venous extracorporeal membrane oxygenation (V-V ECMO) represents a component of the treatment strategy for severe respiratory failure. Clinical evidence on the management of the lung during V-V ECMO are limited just as the consensus regarding timing of weaning. The monitoring of the carbon dioxide (CO2) removal (V′CO2TOT) is subdivided into two components: the membrane lung (ML) and the native lung (NL) are both taken into consideration to evaluate the improvement of the function of the lung and to predict the time to wean off ECMO. We enrolled patients with acute respiratory distress syndrome (ARDS). The V′CO2NL ratio (V′CO2NL/V′CO2TOT) value was calculated based on the distribution of CO2 between the NL and the ML. Of 18 patients, 15 were successfully weaned off of V-V ECMO. In this subgroup, we observed a significant increase in the V′CO2NL ratio comparing the median values of the first and last quartiles (0.32 vs. 0.53, p = 0.0045), without observing any modifications in the ventilation parameters. An increase in the V′CO2NL ratio, independently from any change in ventilation could, despite the limitations of the study, indicate an improvement in pulmonary function and may be used as a weaning index for ECMO.
Veno-Venous Extracorporeal Membrane Oxygenation to Treat Acute Respiratory Distress Syndrome in an Adult with Fontan Palliation
Authors: Fandre Charles , Khairy Paul , Serri Karim , Bouchard Denis , Lamarche Yoan
Published: October 2020

In patients with Fontan palliation, the systemic and pulmonary circulation is in series and supported by a single ventricle, resulting in fragile hemodynamics. Cardiac output is driven by low pressure nonpulsatile pulmonary flow and is highly dependent on pulmonary vascular resistance. An acute respiratory distress syndrome (ARDS) can rapidly alter this physiology and lead to severe cardiogenic shock. Herein, we describe the case of a 40 year old man with a classic modified Fontan procedure and bidirectional Glenn shunt who developed ARDS with cardiogenic shock following a resuscitated cardiac arrest with presumed aspiration pneumonia. In light of poorly tolerated positive end-expiratory pressure ventilation and underlying anatomical complexities, a multidisciplinary team was convened to optimize care. In part owing to the lack of femoral venous access, a veno-venous extracorporeal membrane oxygenation circuit was devised using bilateral internal jugular venous access. Under fluoroscopic guidance in a hybrid operating room, one cannula was placed in the inferior vena cava by means of the right internal jugular venous access, with the second cannula positioned in the right pulmonary artery through the left internal jugular vein. Oxygenation and hemodynamic status promptly improved, allowing the patient to recover from ARDS.
Provider Documentation of Tinnitus in Childhood Cancer Survivors
Authors: Macaruso Natalie , Campbell Kristen , Cost Carrye , Sopfe Jenna
Published: October 2020

Tinnitus is a known complication of treatment for childhood cancer and potentially reduces the quality of life for childhood cancer survivors (CCS). Although current guidelines recommend annual surveillance in CCS at risk for tinnitus, current screening practices among pediatric oncology survivorship providers are unknown. The authors performed a retrospective cohort study to assess the adequacy of current tinnitus screening in survivorship care. The 5.6% prevalence of tinnitus reported by the Childhood Cancer Survivorship Study, the largest ongoing follow-up cohort of CCS, served as the baseline for comparison for our rate of documented positive screening for tinnitus. Survivorship providers identified tinnitus in 3 of 624 (0.48%) eligible CCS, which was significantly lower than the prevalence in the Childhood Cancer Survivorship Study (P<0.0001). Survivorship providers documented any screening for tinnitus (positive or negative) in 15 of 624 (2.4%) CCS. Screening practices significantly differed by ototoxic exposure history and age at follow-up. This study demonstrates that screening and detection of tinnitus are underdocumented by survivorship providers, raising concern for inadequate screening practices. Improved screening may facilitate the recognition and treatment of this late effect, improving the quality of life for CCS.
Family Bereavement Adaptation After Death of a Loved One in an Intensive Care Unit
Authors: La In Seo , Scharf Barbara , Zhu Shijun , Mooney-Doyle Kim , Friedmann Erika , Wiegand Debra L.
Published: October 2020

Limited longitudinal studies have hindered the understanding of family adaptation after loss of a loved one in an intensive care unit (ICU). Based on the Double ABCX Model, this study examined changes in adaptation to bereavement for family members in the first year after the ICU death, with special attention to the effects of race/ethnicity. A repeated-measures design was used to conduct the investigation using 3 time points (1-3, 6, and 12 months) after the ICU death. Data were analyzed using linear mixed modeling. Family members (n = 30) consisted of 60% non-Hispanic Whites and 40% African Americans (AAs). During the first 1 to 3 months, moderate to severe symptoms of posttraumatic stress disorder, depression, anxiety, and stress were found (60%, 40%, 30%, and 26.7%, respectively). Initially, non-Hispanic Whites had higher depression scores than African Americans. The change in depression and posttraumatic stress disorder symptoms over 1 year differed by race/ethnicity. Many family members tended to be at risk of psychological sequelae in the early months after a patient's death in an ICU. Racial/ethnic differences in bereavement process need further exploration to understand the broader context within family members grieve and effectively offer support over the course of the first year.
Nociceptive Flexion Reflex Threshold in Chronic Pain Patients
Authors: Amiri Mohammadreza , Esmaili Hamid , Hamad Abdul Hamid , Alavinia Mohammad , Masani Kei , Kumbhare Dinesh
Published: October 2020

Background

The nociceptive flexion reflex is a physiological, polysynaptic reflex triggered by a nociceptive stimulus activating a withdrawal response. In chronic musculoskeletal-related pain conditions, a decreased nociceptive flexion reflex threshold has been suggested as a possible recognition evidence for central sensitization that may cause alteration of central nervous system processing.

Objective

The aim of the study was to systematically review reported comparisons of the nociceptive flexion reflex threshold in chronic pain patients and healthy individuals.

Methods

Electronic databases covering studies published between January 1990 and December 2019 were systematically searched. After application of exclusion criteria, 20 studies including 28 trials were included in this review. For meta-analysis, we used a random-effects model and funnel plot for publication bias. This research was registered at PROSPERO (CRD42019140354).

Results

Compared with healthy controls, standardized mean differences in nociceptive flexion reflex threshold were significantly lower in the total sample of chronic pain patients. Subgroup analysis indicated a homogenous decreased nociceptive flexion reflex threshold in studies reporting fibromyalgia, chronic pain, and joint pain while heterogeneity existed in other included pain conditions.

Conclusions

A lower nociceptive flexion reflex threshold in patients experiencing chronic pain conditions may imply hyperexcitability in central nervous system processing. As a preliminary study, the findings would act as a basis for developing a methodology assisting current clinical practices
New Insights Into Systemic Lupus Erythematosus Therapies
Authors: Wang Danielle H. , Wallace Daniel J.
Published: October 2020

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that may affect every organ. The multiple pathogenic mechanisms and heterogeneous phenotypes of SLE present unique challenges in the management of this complex disease. This article discusses new SLE therapies from the last 10 years. We will address new information in the realms of lifestyle interventions, antimalarials, nonsteroidal anti-inflammatory drugs, glucocorticoids, immunosuppressive disease modifying antirheumatic drugs, biological therapies, and other modalities as they pertain to SLE.
Tonsillar Metastasis From Colon Cancer Detected on 18F-FDG PET/CT Imaging
Authors: Baghdadi Yaser M. , Valdivia Ana Y.
Published: October 2020

A 54-year-old woman with smoking history who was diagnosed with invasive adenocarcinoma of the rectosigmoid colon with subsequent surgical resection and chemotherapy was presented. The patient developed local recurrence and pulmonary metastases that required further chemotherapy and surgical resection. During follow-up, the patient had 18F-FDG PET/CT scan showing asymmetric hypermetabolic tonsils with activity greater on the right compared with the left. The patient underwent bilateral tonsillectomy, and pathology revealed moderately to poorly differentiated adenocarcinoma in the right tonsil, consistent with metastasis from known colonic primary.
18F-FDG PET/CT in the Diagnosis and Follow-up of Balint Syndrome
Authors: Dondi Francesco , Albano Domenico , Paghera Barbara , Bertagna Francesco , Giubbini Raffaele
Published: October 2020

Balint syndrome is a rare neurological disorder characterized by simultanagnosia, optic ataxia, and ocular apraxia, and its etiology can be very heterogeneous. Diagnosis is based on neuropsychological evaluation, but brain radiological and nuclear medicine imaging also plays an important role. Because few case reports have been published in literature, in this work, we present 2 patients affected by Balint syndrome in which 18F-FDG PET/CT helped in the diagnosis and follow-up.
Integrated Plasma and Tissue Proteomics Reveals Attractin Release by Intraluminal Thrombus of Abdominal Aortic Aneurysms and Improves Aneurysm Growth Prediction in Humans
Authors: Lee Regent , Cassimjee Ismail , Huang Honglei , Lapolla Pierfrancesco , Ngetich Elisha , Chandrashekar Anirudh , Charles Philip , Kessler Benedikt , Fischer Roman , Handa Ashok
Published: October 2020

Objective:

Discovery of novel biomarkers for AAA growth prediction.

Background:

Novel biomarker of AAA growth is a recognized priority in research. Our prior work implicated intraluminal thrombus (ILT) in AAAs to be a potential source of systemic mediators during AAA progression. Here we applied a mass spectrometry proteomics pipeline to discover novel biomarkers for AAA growth prediction.

Methods:

Patients were prospectively recruited. Plasma samples were collected at baseline (n = 62). AAA growth was recorded at 12 months. In Experiment 1, plasma samples from the fastest and slowest growth patients (n = 10 each) were compared. In Experiment 2, plasma samples were collected before and at 10–12 weeks after surgery (n = 29). In Experiment 3, paired ILT and omental biopsies were collected intra-operatively during open surgical repair (n = 3). In Experiment 4, tissue secretome was obtained from ex-vivo culture of these paired tissue samples. Samples were subjected to a liquid chromatography tandem mass spectrometry workflow to discover novel biomarkers.

Results:

We discovered 3 proteins that are: (i) present in ILT; (ii) released by ILT; (iii) reduced in circulation after AAA surgery; (iv) differs between fast and slow growth AAAs. One of these is Attractin. Plasma Attractin correlates significantly with future AAA growth (Spearman r = 0.35, P < 0.005). Using Attractin and AAA diameter as input variables, the area under receiver operating characteristics for predicting no growth and fast growth or AAA at 12 months is 85% and 76%, respectively.

Conclusion:

We show that ILT of AAAs releases mediators during the natural history of AAA growth. These are novel biomarkers for AAA growth prediction in humans.
Multicenter Randomized Phase 2 Trial Comparing Chemoradiotherapy and Docetaxel Plus 5-Fluorouracil and Cisplatin Chemotherapy as Initial Induction Therapy for Subsequent Conversion Surgery in Patients With Clinical T4b Esophageal Cancer
Authors: Sugimura Keijiro , Miyata Hiroshi , Tanaka Koji , Makino Tomoki , Takeno Atsushi , Shiraishi Osamu , Motoori Masaaki , Yamasaki Makoto , Kimura Yutaka , Hirao Motohiro , Fujitani Kazumasa , Yasuda Takushi , Mori Masaki , Eguchi Hidetoshi , Yano Masahiko , Doki Yuichiro
Published: October 2020

Objective:

We conducted a multicenter randomized prospective phase 2 trial of chemoradiotherapy (CRT) versus chemotherapy (CT) as initial induction therapy for conversion surgery (CS) in clinical T4b esophageal cancer. We compared treatment effects and adverse events (AEs).

Summary Background Data:

Although induction followed by CS is potentially curative for T4b esophageal cancer, the optimal initial induction treatment is unclear.

Methods:

Ninety-nine patients with T4b esophageal cancer were randomly allocated to chemoradiotherapy (Group A, n = 49) or CT (Group B, n = 50) as initial induction treatment. CRT consisted of radiation (50.4 Gy) with cisplatin and 5-fluorouracil. CT consisted of 2 cycles of docetaxel plus cisplatin and 5-fluorouracil (DCF). CRT or CT was followed by CS if resectable. If unresectable, the patient received the other treatment as secondary treatment. CS was performed if resectable after secondary treatment. The primary end point was 2-year overall survival.

Results:

In Group A, CS was performed in 34 (69%) and 7 patients (14%) after initial and secondary treatment. In Group B, CS was performed in 25 (50%) and 17 patients (34%) after initial and secondary treatment. The R0 resection rate after initial and secondary treatment was similar (78% vs 76%, P = 1.000). AEs including leukopenia, neutropenia, febrile neutropenia, and diarrhea were significantly more frequent in Group B. Group A had better histological complete response of the primary tumor (40% vs 17%, P = 0.028) and histological nodal status (P = 0.038).

Conclusion:

Upfront CRT was superior to upfront CT in terms of pathological effects and AEs. The Japan Registry of Clinical Trials (s051180164).
Clinical Outcomes After Liver Transplantation in Patients With Portopulmonary Hypertension
Authors: Cartin-Ceba Rodrigo , Burger Charles , Swanson Karen , Vargas Hugo , Aqel Bashar , Keaveny Andrew P. , Heimbach Julie , Taner Timucin , Nyberg Scott , Rosen Charles , Cajigas Hector , DuBrock Hilary , Krowka Michael J.
Published: October 2020

Background.

Portopulmonary hypertension (POPH) is the presence of pulmonary arterial (PA) hypertension in patients with portal hypertension and is associated with significant morbidity and mortality. In a cohort of POPH patients, we describe the clinical outcomes of POPH patients who underwent liver transplantation (LT).

Methods.

Retrospectively collected data from a prospectively assembled cohort of all consecutive POPH adults evaluated in 3 transplant centers from 1996 to 2019.

Results.

From a cohort of 228 POPH patients, 50 patients underwent LT. Significant hemodynamic improvement after PA-targeted therapy was observed, with 58% receiving only monotherapy pretransplant. After LT, 21 (42%) patients were able to discontinue and remained off PA-targeted therapy. The 1-, 3-, and 5-y unadjusted survival rates after LT were 72%, 63%, and 60%, respectively. An elevated pulmonary vascular resistance (PVR) before LT was associated with worse survival rate (HR, 1.91; 95% CI, 1.07-3.74, P = 0.04). No survival difference was observed in those granted MELD exception or transplants performed before or after the year 2010.

Conclusions.

Significant number of POPH patients discontinued PA-targeted therapy after LT. Higher PVR before LT was associated with worse survival, as was monotherapy use. Despite effective PA-targeted therapies, POPH survival outcomes after LT in our cohort were modest and may reflect the need for more aggressive therapy.
Coronin-1 is necessary for enteric pathogen-induced transcytosis across human ileal enteroid monolayers expressing M cells
Authors: Staab Janet F. , Doucet Michele , Latanich Rachel , Lee Sun , Estes Mary K. , Kaper James B. , Zachos Nicholas C.
Published: October 2020

In the intestine, luminal sampling by microfold (M) cells is crucial for inducing protective mucosal immune responses but can also serve as an entry pathway for pathogens, including bacteria and viruses. Enteric pathogens can influence intestinal M cell function; however, the molecular mechanisms involved in the regulation of uptake and transcytosis of gut cargo by human M cells remain to be determined. Understanding the mechanisms responsible for regulating human M cell function requires a relevant human model. In this study, human ileal enteroids established from healthy donors were grown as confluent monolayers on permeable supports and differentiated to express mature M cells. Enteric pathogens including enteropathogenicE. coli(EPEC), adherent invasive E. coli (AIEC), and human rotavirus were apically exposed to M cell enteroid monolayers. M cell-mediated uptake and transcytosis was compared in enteroids infected by pathogenic or commensal bacteria (HS strain). EPEC and AIEC, but not HS, stimulated M cell uptake and transcytosis. We discovered that this pathogenspecific effect was dependent on expression of coronin 1a, a cytoskeletal remodeling protein. Using stable coronin 1a knockdown (KD) enteroids, we observed that EPEC-stimulated transcytosis of fluorescent beads was lost and associated with a significant decrease in the number of glycoprotein-2 positive (Gp-2+ve) M cells. The results of these studies demonstrate that coronin 1a is required for uptake and transcytosis of luminal cargo across human M cells and that coronin 1a is necessary for differentiation of mature M cells that actively transcytose luminal gut antigens in response to pathogenic, but not commensal, microbes.
Polybrominated diphenyl ether serum concentrations and depressive symptomatology in pregnant African American women
Authors: Mutic A. , Barr D. , Hertzberg V. , Dunlop A. , Brennan P. , McCauley L.
Published: October 2020

Background

Polybrominated diphenyl ethers (PBDEs) are lipophilic, persistent endocrine disrupting chemicals often used as flame retardants in products that were widely produced in the United States until 2004. The potential for environmental toxicants such as PBDEs to disrupt normal neuroendocrine pathways resulting in depression and other neurological symptoms has been largely understudied. This study examined whether PBDE exposure in pregnant women was associated with antenatal depressive symptomatology.

Methods

This study is part of a larger longitudinal pregnancy and birth cohort study. Data were collected from 193 African American pregnant women at 8-14 weeks gestation. Serum PBDEs were analyzed using gas chromatography-tandem mass spectrometry. The Edinburgh Depression Scale (EDS) was used to identify depressive symptoms experienced in the last seven days prior to biosampling. The dichotomous depression variable was used to explore varying high-risk EDS cutoffs and illustrated with receiver operating characteristic curves. Logistic regression models were constructed to investigate associations with antenatal depression and a weighted quantile sum (WQS) index was calculated to account for the mixture of PBDE congeners.

Results

Of the total sample, 52 women (26.9%) were categorized as having a high risk of depression. PBDE congeners −47, −99, and −100 were detected in 50% or more of the samples tested. BDE-47 was positively associated with depressive symptoms (β =2.36, p=0.05). The risk of being mild to moderately depressed increased by a factor of 4.52 for BDE-47 (CI 1.50, 13.60) and 1.58 for BDE-99 (CI 1.08, 2.29). The WQS index, a weighted estimate of the body burden of the congener mixture was positively associated with a higher risk of mild to moderate depression using an EDS cutoff ≥10 (OR=2.93; CI 1.18, 7.82).

Conclusion

BDE-47 and −99 exposures are significantly associated with depressive symptomatology in a pregnant cohort. These exposures will likely continue for years due to slow chemical degradation. Interventions should focus on PBDE mitigation to reduce toxic neuroendocrine effects on vulnerable pregnant women.