bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemophagocytic Lymphohistiocytosis in a Patient With Advanced HIV and Cytomegalovirus Infection
Authors: Anabtawi Amir , Alkilany Reem , Lacy Mary E.
Published: February 2020

Hemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive, and, if not treated, fatal disorder that is characterized by excessive immune system activation. This disorder can be precipitated by different triggers including malignancies, infections, and autoimmune disorders. Diagnosis is made by fulfilling criteria that was last updated in 2004, and treatment frequently includes management of the underlying trigger but can also include chemotherapy. In this article, we report a case of HLH in a 27-year-old male, who had been diagnosed with advanced untreated HIV, who presented to the hospital with fever and generalized fatigue with no obvious etiology. Infectious workup revealed cytomegalovirus viremia, and the patient met HLH criteria with impressive hyperferritinemia of 15 432 ng/mL. The patient was started on treatment for cytomegalovirus infection that led to resolution of HLH. Our report highlights the importance of early detection of HLH in special populations, and that treating the presumptive trigger can lead to resolution of HLH.
Cocaine-Induced Ventilation/Perfusion Mismatch Mimicking Pulmonary Embolism
Authors: Surapaneni Phani Keerthi , Abe Temidayo , Fas Norberto
Published: February 2020

Pulmonary complications from cocaine use can range from bronchospasm to vasospasm leading to pulmonary infarction. Profound vasospasm may also lead to perfusion defects presenting as pulmonary embolism on ventilation-perfusion scan. A 65-year-old patient with a past medical history of substance abuse and chronic kidney disease presents to the emergency department with sudden-onset chest pain and shortness of breath. Ventilation-perfusion scan revealed filling defect most notably in the lingual lobe. He was later discharged on warfarin for the management of pulmonary embolism. The patient presented to the emergency department 2 weeks later with similar complaints; the international normalized ratio was subtherapeutic, and urine drug screen was positive for cocaine. Repeat ventilation-perfusion scan revealed no filling defects. Follow-up bilateral venous Doppler of lower extremities and D-dimer were within normal limits.
The Hidden Costs of Teacher Turnover
Authors: Sorensen Lucy C. , Ladd Helen F.
Published: February 2020

High teacher turnover imposes numerous burdens on the schools and districts from which teachers depart. Some of these burdens are explicit and take the form of recruiting, hiring, and training costs. Others are more hidden and take the form of changes to the composition and quality of the teaching staff. This study focuses on the latter. We ask how schools respond to spells of high teacher turnover and assess organizational and human capital effects. Our analysis uses two decades of administrative data on math and English language arts middle school teachers in North Carolina to determine school responses to turnover across different policy environments and macroeconomic climates. Based on models controlling for school contexts and trends, we find that turnover has marked, and lasting, negative consequences for the quality of the instructional staff and student achievement. Our results highlight the need for heightened policy attention to school-specific issues of teacher retention.
Evaluation and Treatment of Chronic Plantar Fasciitis
Authors: Latt L. Daniel , Jaffe David Eric , Tang Yunting , Taljanovic Mihra S.
Published: February 2020

Plantar fasciitis is the most common cause of chronic heel pain in adults, affecting both young active patients and older sedentary individuals. It results from repetitive stress to the plantar fascia at its origin on the medial tubercle of the calcaneus and is often associated with gastrocnemius tightness. The diagnosis can be made clinically with a focused history and physical examination; imaging is reserved for atypical presentations and those that do not respond to initial treatment. The most common presenting symptom is aching plantar heel pain, which is worst with first step in the morning or after periods of rest. Diagnosis is confirmed with point tenderness at the origin of the plantar fascia on the medial tubercle of the calcaneus. Initial treatment consists of activity modification, anti-inflammatory medication, gastrocnemius and plantar fascia stretching, and an in-shoe orthosis that lifts and cushions the heel. These nonoperative treatments lead to complete resolution of pain in 90% of patients but can take 3-6 months. Patients who remain symptomatic despite a 6-month trial of nonoperative therapy may be considered for minimally invasive treatment or surgery. Platelet-rich plasma injections and therapeutic ultrasound are among a number of minimally invasive treatments that stimulate the body’s healing response. Corticosteroid injections temporarily relieve pain, but may increase the risk of plantar fascia rupture and fat pad atrophy. Botulinum toxin injections relax the calf muscles, which decreases the stress in the plantar fascia. Operative treatments include gastrocnemius recession and medial head of gastrocnemius release, which decrease the stress on the plantar fascia and partial planter fasciotomy, which stimulates a healing response.

Level of Evidence:

Level V, expert opinion.
Fractures of the Talus: Current Concepts
Authors: Schwartz Andrew M. , Runge William O. , Hsu Andrew R. , Bariteau Jason T.
Published: February 2020

Talus fractures continue to represent a challenging and commonly encountered group of injuries. Its near-complete articular cartilage surface, and its role in force transmission between the leg and foot, makes successful treatment of such injuries a mandatory prerequisite to regained function. Familiarity with the complex bony, vascular, and neurologic anatomy is crucial for understanding diagnostic findings, treatment indications, and surgical techniques to maximize the likelihood of anatomic bony union. This review details the structure and function of the talus, a proper diagnostic workup, the treatment algorithm, and post-treatment course in the management of talus fractures.

Level of Evidence:

Level V, expert opinion.
Which Cardiac Structure Is Being Captured by Pacing: Atrium, Ventricle, or Something Else?
Authors: Bhargava Kartikeya
Published: February 2020

An interesting electrocardiogram obtained during a cardiac pacing procedure is presented and discussed.
Reversible LV Dysfunction After TAVR
Authors: Arramraju Sreenivas Kumar , Janapati Rama Krishna , Pathakota Sudhakar Reddy , Kumar E Sanjeeva , Mandala Gokul Reddy
Published: February 2020

Aortic stenosis (AS) is characterized by gradual thickening, fibrosis, and calcification leading to reduced opening of aortic valve leaflets. Aortic valve narrowing increases the afterload on left ventricle (LV), which consequently leads to hypertrophy and myocardial fibrosis which over a period of time leads to diastolic dysfunction. LV diastolic dysfunction is an independent predictor of heart failure rehospitalization and mortality in post-aortic valve replacement patients. Chronic pressure overload leads to development of systolic dysfunction due to afterload mismatch. Patients with severe symptomatic AS and depressed LV function without significant myocardial scarring will derive maximum benefit after percutaneous valve replacement and thus show immediate improvement after reduction of LV afterload. We report two such cases which had good LV function recovery immediately after transcatheter aortic valve replacement (TAVR).
Cell quality measurement using cloud computing in case of NiCd/NiMH battery study
Authors: Lin Hsiung-Cheng , Wei Chao-Wei , Chen Hong-Ming
Published: February 2020

Currently, 3.6 V 700 mAh NiCd/NiMH battery is the most popular one used in emergency lights or other devices. It is well known that the state of health is related to the battery internal resistance and charging/discharging characteristics. However, the information needed may not be unveiled sufficiently from the manufactory although some certain specifications are provided. To provide users more accurate information, this system proposes an online battery quality measurement system based on two-pulse approach for internal resistance estimation along with long-term charging/discharging life cycle test. The measurement tasks are carried out using the microprocessor that connects with the computer via universal serial bus. Through the data acquisition system, every measured data from the microprocessor can be immediately transmitted to the data server via transmission control protocol/internet protocol. Accordingly, all testing results can be viewed online from the website, and their history record can be also tracked in the database. The experimental results verify that the proposed scheme can perform the quality measurement effectively and accurately.
What Are the Causes and Cures of Poor Megaproject Performance? A Systematic Literature Review and Research Agenda
Authors: Denicol Juliano , Davies Andrew , Krystallis Ilias
Published: February 2020

This systematic literature review explores the megaproject management literature and contributes by improving our understanding of the causes and cures of poor megaproject performance. The review analyzes 6,007 titles and abstracts and 86 full papers, identifying a total of 18 causes and 54 cures to address poor megaproject performance. We suggest five avenues for future research that should consider examining megaprojects as large-scale, inter-organizational production systems: (1) designing the system architecture; (2) bridging the gap with manufacturing; (3) building and leading collaborations; (4) engaging institutions and communities; and (5) decomposing and integrating the supply chain.
An Authentic Murine Model of Fetal/Neonatal Alloimmune Thrombocytopenia
Authors: Zhi Huiying , Ahlen Maria Therese , Rasmussen Trude , Skogen Bjørn , Newman Peter J.
Published: February 2020

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal antibodies directed against paternally-inherited antigens present on the surface of fetal platelets. The human platelet alloantigen, HPA-1a (also known as the PlA1 alloantigen), is the most frequently implicated HPA for causing FNAIT in Caucasians. A single Leu33Pro amino acid polymorphism residing within the ~50 amino acid plexin/semaphorin/integrin (PSI) domain near the N-terminus of the integrin β3 subunit (platelet membrane glycoprotein (GP)IIIa), is responsible for generating the HPA-1a and HPA-1b epitopes in human GPIIIa. Neither human polyclonal nor mouse monoclonal anti-HPA-1a antibodies, however, recognize murine GPIIIa due to amino acid differences both within and surrounding the HPA-1a alloepitope. As a result, there are currently no authentic mouse models of FNAIT capable of recapitulating the human alloimmune response to this clinically important platelet alloantigen. We have recently shown that humanizing residues 30, 32, 33, and 39 within the PSI domain, as well as amino acid 470 within the linearly distant but conformationally close Epidermal Growth Factor (EGF) 1 domain, of murine GPIIIa, is sufficient to re-create the epitope recognized by most maternal anti-HPA-1a alloantibodies. We therefore used CRISPR/Cas9 gene editing technology to generate transgenic mice whose platelets express human residues A30P32L33D39Q470 on a murine GPIIIa backbone - hereafter referred to as APLDQ mice. Intraperitoneal injection of an anti-HPA-1a mAb induced severe thrombocytopenia in these APLDQ, but not wild-type, mice. Furthermore, platelets from APLDQ mice, when introduced into wild-type mice, elicited a strong polyclonal immune response that was specific for, and importantly restricted to, the epitopes created by these humanized residues, demonstrating that the APLDQ humanized form of murine GPIIIa is immunogenic in mice. Wild-type female mice pre-immunized with APLDQ platelets, when bred with APLDQ male mice, gave birth to severely thrombocytopenic pups, many of whom exhibited an accompanying bleeding phenotype. Notably, administration of intravenous immunoglobulin G (IVIG) into pregnant female mice at days 10 and 17 lowered the concentration of anti-APLDQ alloantibodies in both the maternal and fetal circulation, and importantly normalized the platelet count in the pups. Taken together, these data establish a novel murine model of FNAIT that recapitulates many of the clinically important features of FNAIT. Availability of APLDQ humanized transgenic mice should pave the way for the pre-clinical development and testing of novel therapeutic and prophylactic modalities to treat or prevent FNAIT in humans.

Disclosures

No relevant conflicts of interest to declare.
International consensus guideline for reporting transmission electron microscopy results in the diagnosis of primary ciliary dyskinesia (BEAT PCD TEM Criteria)
Authors: Shoemark Amelia , Boon Mieke , Brochhausen Christoph , Bukowy-Bieryllo Zuzanna , De Santi Maria M. , Goggin Patricia , Griffin Paul , Hegele Richard G. , Hirst Robert A. , Leigh Margaret W. , Lupton Alison , MacKenney Karen , Omran Heymut , Pache Jean-Claude , Pinto Andreia , Reinholt Finn P. , Schroeder Josep , Yiallouros Panayotis , Escudier Estelle
Published: February 2020

Primary ciliary dyskinesia (PCD) is a heterogeneous genetic condition. European and North American diagnostic guidelines recommend transmission electron microscopy (TEM) as one of a combination of tests to confirm a diagnosis. However, there is no definition of what constitutes a defect or consensus on reporting terminology. The aim of this project was to provide an internationally agreed ultrastructural classification for PCD diagnosis by TEM.

A consensus guideline was developed by PCD electron microscopy experts representing 18 centres in 14 countries. An initial meeting and discussion were followed by a Delphi consensus process. The agreed guideline was then tested, modified and retested through exchange of samples and electron micrographs between the 18 diagnostic centres.

The final guideline a) provides agreed terminology and a definition of Class 1 defects which are diagnostic for PCD; b) identifies Class 2 defects which can indicate a diagnosis of PCD in combination with other supporting evidence; c) describes features which should be included in a ciliary ultrastructure report to assist multidisciplinary diagnosis of PCD; and d) defines adequacy of a diagnostic sample.

This tested and externally validated statement provides a clear guideline for the diagnosis of PCD by TEM which can be used to standardise diagnosis internationally.
α1Antitrypsin therapy modulates the neutrophil membrane proteome and secretome
Authors: Murphy Mark P. , McEnery Thomas , McQuillan Karen , McElvaney Oisín F. , McElvaney Oliver J. , Landers Sarah , Coleman Orla , Bussayajirapong Anchalin , Hawkins Padraig , Henry Michael , Meleady Paula , Reeves Emer P. , McElvaney Noel G.
Published: February 2020

Obstructive pulmonary disease in patients with α1antitrypsin (AAT) deficiency (AATD) occurs earlier in life compared with patients without AATD. To understand this further, the aim of this study was to investigate whether AATD presents with altered neutrophil characteristics, due to the specific lack of plasma AAT, compared with non-AATD COPD.

This study focussed on the neutrophil plasma membrane and, by use of label-free tandem mass spectrometry, the proteome of the neutrophil membrane was compared in forced expiratory volume in 1 s (FEV1)-matched AATD, non-AATD COPD and in AATD patients receiving weekly AAT augmentation therapy (n=6 patients per cohort). Altered protein expression in AATD was confirmed by Western blot, ELISA and fluorescence resonance energy transfer analysis.

The neutrophil membrane proteome in AATD differed significantly from that of COPD as demonstrated by increased abundance and activity of primary granule proteins including neutrophil elastase on the cell surface in AATD. The signalling mechanism underlying increased degranulation involved Rac2 activation, subsequently resulting in proteinase-activated receptor 2 activation by serine proteinases and enhanced reactive oxygen species production.In vitroandex vivo, AAT reduced primary granule release and the described plasma membrane variance was resolved post-AAT augmentation therapyin vivo, the effects of which significantly altered the AATD neutrophil membrane proteome to that of a non-AATD COPD cell.

These results provide strong insight into the mechanism of neutrophil driven airways disease associated with AATD. Therapeutic AAT augmentation modified the membrane proteome to that of a typical COPD cell, with implications for clinical practice.
Acute exacerbation of idiopathic pulmonary fibrosis: international survey and call for harmonisation
Authors: Kreuter Michael , Polke Markus , Walsh Simon L.F. , Krisam Johannes , Collard Harold R. , Chaudhuri Nazia , Avdeev Sergey , Behr Jürgen , Calligaro Gregory , Corte Tamera , Flaherty Kevin , Funke-Chambour Manuela , Kolb Martin , Kondoh Yasuhiro , Maher Toby M. , Molina Molina Maria , Morais Antonio , Moor Catharina C. , Morisset Julie , Pereira Carlos , Quadrelli Silvia , Selman Moises , Tzouvelekis Argyrios , Valenzuela Claudia , Vancheri Carlo , Vicens-Zygmunt Vanesa , Wälscher Julia , Wuyts Wim , Wijsenbeek Marlies , Cottin Vincent , Bendstrup Elisabeth
Published: February 2020

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an often deadly complication of IPF. No focussed international guidelines for the management of AE-IPF exist. The aim of this international survey was to assess the global variability in prevention, diagnostic and treatment strategies for AE-IPF.

Pulmonologists with ILD expertise were invited to participate in a survey designed by an international expert panel.

509 pulmonologists from 66 countries responded. Significant geographical variability in approaches to manage AE-IPF was found. Common preventive measures included antifibrotic drugs and vaccination. Diagnostic differences were most pronounced regarding use of Krebs von den Lungen-6 and viral testing, while high-resolution computed tomography, brain natriuretic peptide and D-dimer are generally applied. High-dose steroids are widely administered (94%); the use of other immunosuppressant and treatment strategies is highly variable. Very few (4%) responders never use immunosuppression. Antifibrotic treatments are initiated during AE-IPF by 67%. Invasive ventilation or extracorporeal membrane oxygenation are mainly used as a bridge to transplantation. Most physicians educate patients comprehensively on the severity of AE-IPF (82%) and consider palliative care (64%).

Approaches to the prevention, diagnosis and treatment of AE-IPF vary worldwide. Global trials and guidelines to improve the prognosis of AE-IPF are needed.
Potential therapeutic targets for lung repair during humanex vivolung perfusion
Authors: Wong Aaron , Zamel Ricardo , Yeung Jonathan , Bader Gary D. , Dos Santos Claudia C. , Bai Xiaohui , Wang Yubo , Keshavjee Shaf , Liu Mingyao
Published: February 2020

Introduction

Theex vivolung perfusion (EVLP) technique has been developed to assess the function of marginal donor lungs and has significantly increased donor lung utilisation. EVLP has also been explored as a platform for donor lung repair through injury-specific treatments such as antibiotics or fibrinolytics. We hypothesised that actively expressed pathways shared between transplantation and EVLP may reveal common mechanisms of injury and potential therapeutic targets for lung repair prior to transplantation.

Materials and methods

Retrospective transcriptomics analyses were performed with peripheral tissue biopsies from “donation after brain death” lungs, with 46 pre-/post-transplant pairs and 49 pre-/post-EVLP pairs. Pathway analysis was used to identify and compare the responses of donor lungs to transplantation and to EVLP.

Results

22 pathways were enriched predominantly in transplantation, including upregulation of lymphocyte activation and cell death and downregulation of metabolism. Eight pathways were enriched predominantly in EVLP, including downregulation of leukocyte functions and upregulation of vascular processes. 27 pathways were commonly enriched, including activation of innate inflammation, cell death, heat stress and downregulation of metabolism and protein synthesis. Of the inflammatory clusters, Toll-like receptor/innate immune signal transduction adaptor signalling had the greatest number of nodes and was central to inflammation. These mechanisms have been previously speculated as major mechanisms of acute lung injury in animal models.

Conclusion

EVLP and transplantation share common molecular features of injury including innate inflammation and cell death. Blocking these pathways during EVLP may allow for lung repair prior to transplantation.
Fluctuations in local and widespread mechanical sensitivity throughout the migraine cycle: a prospective longitudinal study
Authors: Scholten-Peeters Gwendolyne G. M. , Coppieters Michel W. , Durge Tom S. C. , Castien René F.
Published: February 2020

Background

People with migraine have localised (i.e., cephalic) mechanical sensitivity. There is uncertainty regarding widespread (i.e., extra-cephalic) mechanical sensitivity and variations in mechanical sensitivity throughout the migraine cycle. Therefore, this study aimed (1) to comprehensively assess mechanical sensitivity in both cephalic and extra-cephalic regions during the preictal, ictal, postictal and interictal phases; and (2) to compare these findings with mechanical sensitivity at corresponding time-points and locations in healthy participants.

Methods

According to sample size calculations, 19 people with migraine and 19 matched healthy volunteers participated in a prospective longitudinal study. Pressure pain thresholds were evaluated in three cephalic regions (temporalis, upper trapezius and C1 paraspinal muscles) and two extra-cephalic regions (extensor carpi radialis and tibialis anterior muscle) with a digital algometer during the four phases of the migraine cycle in people with migraine and at corresponding intervals and locations in healthy participants. Linear mixed model analyses with a random intercept were used.

Results

People with migraine had increased mechanical sensitivity in cephalic and extra-cephalic regions in all phases of the migraine cycle compared to healthy participants. Furthermore, this mechanical sensitivity was more severe in the preictal, ictal and postictal phase compared to the interictal phase in cephalic and extra-cephalic regions.

Conclusion

People with migraine have localised as well as widespread mechanical sensitivity compared to healthy participants. This sensitivity is even more pronounced immediately before, during and after a migraine attack.
QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with coronary heart disease (QUEL): protocol for a 24-month cluster randomised controlled trial in primary care
Authors: Redfern Julie , Hafiz Nashid , Hyun Karice , Knight Andrew , Hespe Charlotte , Chow Clara K. , Briffa Tom , Gallagher Robyn , Reid Christopher , Hare David L. , Zwar Nicholas , Woodward Mark , Jan Stephen , Atkins Emily R. , Laba Tracey-Lea , Halcomb Elizabeth , Billot Laurent , Johnson Tracey , Usherwood Timothy
Published: February 2020

Background

Cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, is the leading cause of death and disability globally. A large proportion of mortality occurs in people with prior CHD and effective and scalable strategies are needed to prevent associated deaths and hospitalisations. The aim of this study is to determine if a practice-level collaborative quality improvement program, focused on patients with CHD, reduces the rate of unplanned CVD hospitalisations and major adverse cardiovascular events, and increases the proportion of patients achieving risk factor targets at 24 months.

Methods

Cluster randomised controlled trial (cRCT) to evaluate the effectiveness of a primary care quality improvement program in 50 primary care practices (n~ 10,000 patients) with 24-month follow-up. Eligible practices will be randomised (1:1) to participate in either the intervention (collaborative quality improvement program) or control (standard care) regimens. Outcomes will be assessed based on randomised allocation, according to intention-to-treat. The primary outcome is the proportion of patients with unplanned CVD hospitalisations at 2 years. Secondary outcomes are proportion of patients with major adverse cardiovascular events, proportion of patients who received prescriptions for guideline-recommended medicines, proportion of patients achieving national risk factor targets and proportion with a chronic disease management plan or review. Differences in the proportion of patients who are hospitalised (as well as binary secondary outcomes) will be analysed using log-binomial regression or robust Poisson regression, if necessary.

Discussion

Despite extensive research with surrogate outcomes, to the authors’ knowledge, this is the first randomised controlled trial to evaluate the effectiveness of a data-driven collaborative quality improvement intervention on hospitalisations, CVD events and cardiovascular risk amongst patients with CHD in the primary care setting. The use of data linkage for collection of outcomes will enable evaluation of this potentially efficient strategy for improving management of risk and outcomes for people with heart disease.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) numberACTRN12619001790134(dated 20th December 2019).
Gastric schwannoma with giant ulcer and lymphadenopathy mimicking gastric cancer: a case report
Authors: Tang Caihua , Pan Qiyong , Xu Zeqing , Zhou Xuan , Wang Ying
Published: February 2020

Background

Gastric schwannomas are rare benign tumors originating from the intramuscular plexus of the stomach and account for just 2.6% of gastric mesenchymal tumors. Gastric schwannoma (GS) with a surface ulcer is very rare. Herein, we report a rare case of an ulcer-bearing GS, which in conjunction with multiple enlarged regional lymph nodes, readily mimicked gastric cancer (GC).

Case presentation

A 79-year-old female presented with poor appetite and intermittent vomiting of gastric contents during the past month. Gastroscopy revealed a giant crateriform ulcer within the stomach body (at the angular notch). Its raised and indurated border was fragile and bled easily. GC was thus suspected. Contrast-enhanced computer tomography (CT) revealed a mild enhancement of the corresponding irregularly thickened gastric wall, and an annular zone of mucosal discontinuity. Enlarged regional lymph nodes were also found, making GC with metastases of lymph nodes our primary concern. 18F-fluorodeoxyglueose position emission tomography (18F-FDG PET)/CT was then performed for further staging. Obviously increased FDG uptake was shown in the gastric lesion ((maximum standardized uptake value (SUVmax) 14.6), but no FDG uptake was observed in the enlarged regional lymph nodes. Given the strong suspicion of GC, subtotal gastrectomy was performed. GS was revealed by postoperative pathology, with no evidence of metastasis in the 13 resected lymph nodes.

Conclusions

This was a rare case of GS with a giant surface ulcer and multiple enlarged regional lymph nodes. The uptake of 18F-FDG in the tumor was substantially higher than previously published literature reports. Under these circumstances, it is difficult to be differentiated from GC.
The diagnosis “failure to thrive” and its impact on the care of hospitalized older adults: a matched case-control study
Authors: Tsui Clara , Kim Kristine , Spencer Martha
Published: February 2020

Background

“Failure to thrive” and associated diagnoses are non-specific terms applied to older adults when there is lack of diagnostic clarity and imply an absence of medical acuity. We investigated the effect of such admission diagnoses on delivery of patient care in a cohort of older adults admitted to a tertiary care teaching hospital.

Methods

Retrospective matched cohort study conducted at a tertiary care hospital in Vancouver, BC. Cases identified were adults aged ≥65 years admitted to acute medical wards with an admission diagnosis of “failure to thrive”, “FTT”, “failure to cope”, or “FTC”, between January 1, 2016 and November 1, 2017 (n = 60, median age 80 years). Age-matched controls met the same inclusion criteria with admission diagnoses other than those of interest (n = 60, median age 79 years).

Results

The primary outcome was time to admission, measured from time points in the emergency room that spanned from triage to completion of admission orders. Secondary outcomes were concordance of admission and discharge diagnoses and length of stay in hospital.

The total time from triage to admission for older adults admitted with FTT and associated diagnoses was 10 h 40 min, compared to 6 h 58 min for controls (p = .02). Concordance of admission and discharge diagnoses was only 12% for the “failure to thrive” cohort, and 95% for controls. Notably, 88% of the “failure to thrive” cohort had an acute medical diagnosis at the time of discharge. Patients in this cohort stayed 18.3 days in hospital compared to 10.2 days (p = .001).

Conclusions

Patients with an admission diagnosis of FTT or other associated diagnoses had significant delays in care when presenting to the emergency room, despite often having acute medical conditions on presentation. The use of this non-specific label can lead to premature diagnostic closure and should be avoided in clinical practice.
Comorbidities associated with HPV infection among people living with HIV-1 in the southeastern US: a retrospective clinical cohort study
Authors: Ye Yuanfan , Burkholder Greer A. , Wiener Howard W. , Griffin Russell , Aslibekyan Stella , Fry Karen , Khan Ashraf , Shrestha Sadeep
Published: February 2020

Background

The southeastern US is an epicenter for incident HIV in the US with high prevalence of human papillomavirus (HPV) co-infections. However, epidemiologies of HPV-associated clinical conditions (CC) among people living with HIV-1 infection (PLWH) are not fully known.

Methods

Electronic medical records (EMR) of PLWH attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analyzed. The retrospective study was nested within the University of Alabama at Birmingham HIV clinical cohort, which has electronically collected over 7000 PLWH’s clinical and sociobehavioral data since 1999. Incidence rates of HPV-related CC including anogenital warts, penile, anal, cervical, and vaginal/vulvar low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) were estimated per 10,000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of incident CC. All rates and trends were stratified by gender and race.

Results

Of the 4484 PLWH included in the study (3429 men, 1031 women, and 24 transgender), we observed 1038 patients with HPV-related CC. The median nadir CD4 count (cells/uL) was higher in the HPV-condition free group than the case groups (P < 0.0001). Anogenital warts, anal LSIL, HSIL, and cancer were more likely to be diagnosed among HIV-infected men than women. White men presented more frequently with anal LSIL and anal and penile cancers than black men (P < 0.03). White women were also more likely to be diagnosed with cervical HSIL (P = 0.023) and cancer (P = 0.037) than black women.

Conclusions

There were significant differences between gender and race with incidence of HPV-related CC among HIV patients. EMR-based studies provide insights on understudied HPV-related anogenital conditions in PLWH; however, large-scale studies in other regions are needed to generalize current findings and draw public health attention to co-infection induced non-AIDS defining comorbidities among PLWH.
Fatal acute Chagas disease by Trypanosoma cruzi DTU TcI, Ecuador
Authors: Calvopina Manuel , Segovia Gabriela , Cevallos William , Vicuña Yosselin , Costales Jaime A. , Guevara Angel
Published: February 2020

Background

Chagas disease is caused by the haemoflagellate protozoan Trypanosoma cruzi. Currently, T. cruzi recognizes seven discrete typing units (DTUs): TcI to TcVI and Tcbat. The genetic diversity of T. cruzi is suspected to influence the clinical outcome. Acute clinical manifestations, which include myocarditis and meningoencephalitis, are sometimes fatal; occur most frequently in children and in immunocompromised individuals. Acute disease is often overlooked, leading to a poor prognosis.

Case presentation

A 38-year-old man from a subtropical area of the Andes mountains of Ecuador was hospitalized after 3 weeks of evolution with high fever, chills, an enlarged liver, spleen, and lymph nodes, as well as facial edema. ECG changes were also observed. T. cruzi was identified in blood smears, culture and amplification of DNA by PCR. Tests for anti-T. cruzi IgG and IgM and HIV were negative. Molecular typing by restriction fragment length polymorphism (PCR-RFLP) determined the parasite to DTU TcI. In the absence of a timely anti-T. cruzi medication, the patient died.

Conclusions

This is a case of severe pathogenicity and the virulence of a DTU TcI strain in an adult patient. The severe acute Chagas disease was probably overlooked due to limited awareness and its low incidence. Our findings suggest that T. cruzi DTU TcI strains circulating in Ecuador are capable of causing fatal acute disease. Early diagnosis and prompt treatment is of paramount importance to avoid fatalities in acute infections.
Prevalence and mortality of cryptococcal disease in adults with advanced HIV in an urban tertiary hospital in Sierra Leone: a prospective study
Authors: Lakoh Sulaiman , Rickman Hannah , Sesay Momodu , Kenneh Sartie , Burke Rachael , Baldeh Mamadu , Jiba Darlinda F. , Tejan Yusuf S. , Boyle Sonia , Koroma Comfort , Deen Gibrilla F. , Beynon Fenella
Published: February 2020

Background

The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/μl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone.

Methods

A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm3 from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher’s exact test was used to compare categorical variables.

Results

A total of 170 patients, with median age of 36 (IQR 30–43) and median CD4 count of 45 cells/mm3 (IQR 23–63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4–9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks.

Conclusion

A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.
Salivary epigenetic biomarkers as predictors of emerging childhood obesity
Authors: Rushing Amanda , Sommer Evan C. , Zhao Shilin , Po’e Eli K. , Barkin Shari L.
Published: February 2020

Background

Epigenetics could facilitate greater understanding of disparities in the emergence of childhood obesity. While blood is a common tissue used in human epigenetic studies, saliva is a promising tissue. Our prior findings in non-obese preschool-aged Hispanic children identified 17 CpG dinucleotides for which differential methylation in saliva at baseline was associated with maternal obesity status. The current study investigated to what extent baseline DNA methylation in salivary samples in these 3–5-year-old Hispanic children predicted the incidence of childhood obesity in a 3-year prospective cohort.

Methods

We examined a subsample (n = 92) of Growing Right Onto Wellness (GROW) trial participants who were randomly selected at baseline, prior to randomization, based on maternal phenotype (obese or non-obese). Baseline saliva samples were collected using the Oragene DNA saliva kit. Objective data were collected on child height and weight at baseline and 36 months later. Methylation arrays were processed using standard protocol. Associations between child obesity at 36 months and baseline salivary methylation at the previously identified 17 CpG dinucleotides were evaluated using multivariable logistic regression models.

Results

Among the n = 75 children eligible for analysis, baseline methylation of Cg1307483 (NRF1) was significantly associated with emerging childhood obesity at 36-month follow-up (OR = 2.98, p = 0.04), after adjusting for child age, gender, child baseline BMI-Z, and adult baseline BMI. This translates to a model-estimated 48% chance of child obesity at 36-month follow-up for a child at the 75th percentile of NRF1 baseline methylation versus only a 30% chance of obesity for a similar child at the 25th percentile. Consistent with other studies, a higher baseline child BMI-Z during the preschool period was associated with the emergence of obesity 3 years later, but baseline methylation of NRF1 was associated with later obesity even after adjusting for child baseline BMI-Z.

Conclusions

Saliva offers a non-invasive means of DNA collection and epigenetic analysis. Our proof of principle study provides sound empirical evidence supporting DNA methylation in salivary tissue as a potential predictor of subsequent childhood obesity for Hispanic children. NFR1 could be a target for further exploration of obesity in this population.
Testicular expression of TDRD1, TDRD5, TDRD9 and TDRD12 in azoospermia
Authors: Babakhanzadeh Emad , Khodadadian Ali , Rostami Saadi , Alipourfard Iraj , Aghaei Mohsen , Nazari Majid , Hosseinnia Mehdi , Mehrjardi Mohammad Yahya Vahidi , Jamshidi Yalda , Ghasemi Nasrin
Published: February 2020

Background

Tudor domain-containing proteins (TDRDs) play a critical role in piRNA biogenesis and germ cell development. piRNAs, small regulatory RNAs, act by silencing of transposons during germline development and it has recently been shown in animal model studies that defects in TDRD genes can lead to sterility in males.

Methods

Here we evaluate gene and protein expression levels of four key TDRDs (TDRD1, TDRD5, TDRD9 and TDRD12) in testicular biopsy samples obtained from men with obstructive azoospermia (OA, n = 29), as controls, and various types of non-obstructive azoospermia containing hypospermatogenesis (HP, 28), maturation arrest (MA, n = 30), and Sertoli cell-only syndrome (SCOS, n = 32) as cases. One-way ANOVA test followed by Dunnett’s multiple comparison post-test was used to determine inter-group differences in TDRD gene expression among cases and controls.

Results

The results showed very low expression of TDRD genes in SCOS specimens. Also, the expression of TDRD1 and TDRD9 genes were lower in MA samples compared to OA samples. The expression of TDRD5 significantly reduced in SCOS, MA and HP specimens than the OA specimens. Indeed, TDRD12 exhibited a very low expression in HP specimens in comparison to OA specimens. All these results were confirmed by Western blot technique.

Conclusion

TDRDs could be very important in male infertility, which should be express in certain stages of spermatogenesis.
Immunogenomic pathways associated with cytotoxic lymphocyte infiltration and survival in colorectal cancer
Authors: Shen Yuanyuan , Guan Yue , Hummel Justin J. , Shyu Chi-Ren , Mitchem Jonathan B.
Published: February 2020

Background

Colorectal cancer (CRC) is the second leading cancer killer in the US today and patients with metastatic disease have only a 14% 5-year survival. One of the most impactful recent advances in cancer therapy, immune checkpoint inhibition, has not been shown to be effective for the majority of these patients. In this study, we use The Cancer Genome Atlas (TCGA) and recently developed informatic-based tools to identify targets for immune based therapy in colorectal cancer patients.

Methods

Open access, pre-processed (level 3) mRNA data and clinical data from colorectal patients from the TCGA was downloaded from FireCloud. Using the Microenvironment Cell Populations-Counter method (MCP-Counter), cytotoxic lymphocyte scores were calculated for all patients. Patients were then grouped by cytotoxic lymphocyte score (High vs Low), pathologic stage, and location to identify differentially expressed genes. Pathway enrichment analysis was performed using Reactome to determine differentially expressed genes associated with immune pathways. Survival analysis was performed with identified differentially expressed genes.

Results

In the TCGA dataset, there are 461 colon and 172 rectal cancer patients. After stratifying patients by cytotoxic lymphocyte score, anatomical location, and stage, we found a significant number of differentially expressed genes. We identified one pathway, “immunoregulatory interactions between a lymphoid and non-lymphoid cell”, that was highly enriched and included in all tumor locations and stages. Survival analysis performed with differentially expressed genes in this pathway identified 21 different genes associated with survival and cytotoxic lymphocyte infiltration, with ~ 70% of these genes occurring in the metastatic right-sided CRC group. Specifically, all genes associated with survival in the metastatic right-sided colorectal cancer group with low cytotoxic lymphocyte scores positively impacted survival.

Conclusions

Utilizing the TCGA, a publicly available dataset, and informatics-based analyses, we identified potential targets to improve immune based therapy in colorectal cancer. Additionally, we note the most targets in metastatic right-sided CRC patients, the patient group with the worst predicted survival. The results from this study demonstrate the ability of informatics-based analytic techniques to identify new therapeutic targets as well as improve patient selection for intervention, helping us to achieve the goals of precision-based oncology.
Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial
Authors: Nichols Anthony C. , Lang Pencilla , Prisman Eitan , Berthelet Eric , Tran Eric , Hamilton Sarah , Wu Jonn , Fung Kevin , de Almeida John R. , Bayley Andrew , Goldstein David P. , Eskander Antoine , Husain Zain , Bahig Houda , Christopoulous Apostolos , Hier Michael , Sultanem Khalil , Richardson Keith , Mlynarek Alex , Krishnan Suren , Le Hien , Yoo John , MacNeil S. Danielle , Mendez Adrian , Winquist Eric , Read Nancy , Venkatesan Varagur , Kuruvilla Sara , Warner Andrew , Mitchell Sylvia , Corsten Martin , Rajaraman Murali , Johnson-Obaseki Stephanie , Eapen Libni , Odell Michael , Chandarana Shamir , Banerjee Robyn , Dort Joseph , Matthews T. Wayne , Hart Robert , Kerr Paul , Dowthwaite Samuel , Gupta Michael , Zhang Han , Wright Jim , Parker Christina , Wehrli Bret , Kwan Keith , Theurer Julie , Palma David A.
Published: February 2020

Background

Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches.

Methods

This is a multicenter phase II study randomizing one hundred and forty patients with T1–2 N0–2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50–60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity.

Discussion

This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials.

Trial Registration

Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.
Laboratory evaluation of the optical properties of two extended-depth-of-focus intraocular lenses
Authors: Chae Sue Hey , Son Hyeck Soo , Khoramnia Ramin , Lee Kyung Heon , Choi Chul Young
Published: February 2020

Background

To experimentally compare the optical performance of two different Extended-Depth-of-Focus (EDOF) intraocular lenses (IOLs) using a standardized optical bench set-up.

Methods

In this experimental study, following IOLs were assessed: the TECNIS® Symfony ZXR00 (Johnson&Johnson, Santa Ana, USA) and the AT LARA 829MP (Carl Zeiss Meditec, Jena, Germany) IOLs. The through-focus modulation transfer function (MTF) values were measured at a spatial frequency of 50 lp/mm and at aperture sizes of 2, 3, and 4.5 mm. Each IOL was measured while centered using ISO 11979-2 Model 1 (aberration-free) and Model 2 (+ 0.28 μm spherical aberration) corneas. United States Air Force (USAF) target images were also recorded for a qualitative evaluation.

Results

At 2 mm pupil with ISO1 cornea, the primary and secondary foci of both IOLs appeared to merge, providing an elongated depth of focus. At 3 and 4.5 mm pupil sizes, the through-focus MTF curves of both IOLs showed a bifocal-like V-pattern. While the Symfony IOL showed an overall superior MTF values when measured with the ISO2 cornea, the opposite propensity could be observed with the AT LARA IOL. This optical behavior could be qualitatively confirmed by the USAF target images.

Conclusions

Although the two EDOF IOLs share similarities in their optical properties, the main difference lies in their optical design and performance with respect to spherical aberration. Such characteristics should be taken into account during IOL and patient selection.