bluuebunny/crossref_metadata_2025 huggingface dataset:
Sonographic assessment of cartilage damage at the metacarpal head in rheumatoid arthritis: qualitative versus quantitative methods
Authors: Cipolletta Edoardo , Mandl Peter , Di Matteo Andrea , Mashadi Mirza Riccardo , Passarini Giancarlo , Grassi Walter , Filippucci Emilio
Published: June 2021

Objective

To test the validity of the OMERACT semi-quantitative score by comparing with a quantitative method in the US assessment of hyaline cartilage at the metacarpal head (MH) in patients with RA and healthy controls (HCs).

Methods

The hyaline cartilage from the second to fifth MHs of both hands was scanned. Hyaline cartilage was scored semi-quantitatively and quantitatively by measuring cartilage thickness and comparing with reference values. In RA patients, radiographic joint space narrowing (JSN) was scored on the same joints using the Simple Erosion Narrowing Score (SENS).

Results

A total of 408 MHs in 51 RA patients and 320 MHs in 40 HSs were evaluated. The OMERACT semi-quantitative score was quicker to perform than the quantitative method [6.0 min (s.d. 0.5) vs 8.0 (1.5); P < 0.01]. A significant correlation between the US scores (R = 0.68) and between the US scores and the JSN-SENS (R = 0.61 and R = 0.63 for the semi-quantitative and quantitative method, respectively) was found. The frequency of cartilage abnormalities was similar between the two US methods in RA patients (58.8% and 51.0% of RA patients for the semi-quantitative and quantitative method, respectively; P = 0.46), while the former revealed more abnormalities in HCs (27.5% and 7.5% of HCs; P = 0.02).

Conclusion

The higher feasibility of the OMERACT semi-quantitative score suggests its use as a first-choice method in the evaluation of cartilage damage. However, despite its limits, the quantitative assessment of HCs, providing patient-tailored information with age- and sex-corrected cut-off values, may represent a valid supplement for optimizing the evaluation of cartilage damage in selected cases.
Altered functional connectivity during face processing in children born with very low birth weight
Authors: Sato Julie , Safar Kristina , Vandewouw Marlee M , Bando Nicole , O’Connor Deborah L , Unger Sharon L , Taylor Margot J
Published: June 2021

Structural brain alterations have been reported in key emotional face processing regions following preterm birth; however, few studies have investigated the functional networks underlying these processes in children born with very low birth weight (VLBW). Using magnetoencephalography (MEG), we examined the functional networks related to the implicit processing of happy and angry faces in 5-year-old VLBW (n = 28) and full-term (FT; n = 24) children. We found that VLBW children showed atypical recruitment of emotional face processing networks in theta (4–7 Hz) compared to FT children. VLBW children showed reduced theta connectivity during processing of angry faces only. This hypo-connected theta-band network was anchored in the left orbitofrontal and parietal regions, involved in the higher level processing of faces and emotion regulation. At the behavioural level, despite VLBW children performing within the normal range, FT children had significantly higher affect recognition scores. Our MEG results suggest a selective impairment in processing angry faces, which would negatively impact social functioning in VLBW children. In FT children, greater recruitment of this theta-band network was positively associated with improved affect recognition scores. Thus, our findings suggest an important role of theta oscillations in early face processing, deficits which may contribute to broader socio-emotional impairments in VLBW children.
Developmental Exposure to Domoic Acid Disrupts Startle Response Behavior and Circuitry in Zebrafish
Authors: Panlilio Jennifer M , Jones Ian T , Salanga Matthew C , Aluru Neelakanteswar , Hahn Mark E
Published: June 2021

Harmful algal blooms produce potent neurotoxins that accumulate in seafood and are hazardous to human health. Developmental exposure to the harmful algal bloom toxin, domoic acid (DomA), has behavioral consequences well into adulthood, but the cellular and molecular mechanisms of DomA developmental neurotoxicity are largely unknown. To assess these, we exposed zebrafish embryos to DomA during the previously identified window of susceptibility and used the well-known startle response circuit as a tool to identify specific neuronal components that are targeted by exposure to DomA. Exposure to DomA reduced startle responsiveness to both auditory/vibrational and electrical stimuli, and even at the highest stimulus intensities tested, led to a dramatic reduction of one type of startle (short-latency c-starts). Furthermore, DomA-exposed larvae had altered kinematics for both types of startle responses tested, exhibiting shallower bend angles and slower maximal angular velocities. Using vital dye staining, immunolabeling, and live imaging of transgenic lines, we determined that although the sensory inputs were intact, the reticulospinal neurons required for short-latency c-starts were absent in most DomA-exposed larvae. Furthermore, axon tracing revealed that DomA-treated larvae also showed significantly reduced primary motor neuron axon collaterals. Overall, these results show that developmental exposure to DomA targets large reticulospinal neurons and motor neuron axon collaterals, resulting in measurable deficits in startle behavior. They further provide a framework for using the startle response circuit to identify specific neural populations disrupted by toxins or toxicants and to link these disruptions to functional consequences for neural circuit function and behavior.
Complete Genome of Xanthomonas arboricola pv. corylina Strain A7 Isolated from Southern Chile
Authors: Núñez Pablo , Muster Cecilia , Lisperguer María José , Vargas Ester , Bustos Sofia
Published: June 2021

The complete genome sequence of Xanthomonas arboricola pv. corylina A7 was obtained by a hybrid approach combining PacBio and Illumina HiSeq sequence data. A single circular chromosome of 5.1 mb with 65.47% G + C content was obtained, including 4,344 coding sequences identified as well as some genes involved in copper resistance. The information obtained corresponds to the first report of a high-quality whole genome of X. arboricola pv. corylina, isolated from infected hazelnut trees in southern Chile.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Prevalence and Genetic Diversity of Viruses Associated with Rugose Wood Complex in Greek Vineyards
Authors: Orfanidou C. G. , Moraki K. , Panailidou P. , Lotos L. , Katsiani A. , Avgelis A. , Katis N. I. , Maliogka V. I.
Published: June 2021

Rugose wood is one of the most important disease syndromes of grapevine, and it has been associated with at least three viruses: grapevine rupestris stem pitting-associated virus (GRSPaV), grapevine virus A (GVA), and grapevine virus B (GVB). All three viruses show a worldwide distribution pattern, and their genetic composition has been the focus of extensive research in past years. Despite their first record in Greece almost 20 years ago, there is a lack of knowledge on the distribution and genetic variability of their populations in Greek vineyards. In this context, we investigated the distribution of GRSPaV, GVA, and GVB in rootstocks, self-rooted vines, and grafted grapevine cultivars originating from different geographic regions that represent important viticultural areas of Greece. Three new reverse transcription-PCR assays were developed for the reliable detection of GRSPaV, GVA, and GVB. Our results indicated that GVA is the most prevalent in Greek vineyards, followed by GRSPaV and GVB. However, virus incidence differed among self-rooted and grafted grapevine cultivars or rootstocks tested. Selected isolates from each virus were further molecularly characterized to determine their phylogenetic relationships. All three viruses exhibited high nucleotide diversity, which was depicted in the constructed phylogenetic trees. Isolates from Greece were placed in various phylogroups, reinforcing the scenario of multiple introductions of GVA, GVB, and GRSPaV in Greece and highlighting the effect of different transmission modes in the evolutionary course of the three viruses.
Living with Lyme disease
Authors: Adams Lucy , Evans Michael M. , Riley Kiernan , Kowalchik Kaléi , Lucey Megan , DeSanto Logan
Published: June 2021

Learn how to recognize posttreatment Lyme disease syndrome, which occurs when Lyme disease symptoms last for more than 6 months after the infection is gone.
Seeing Past the Sentence
Authors: McCormick Robin , Painter Leslie
Published: June 2021

The number of women who are incarcerated in the United States has grown significantly since 1980. Caring for pregnant women who are in the correctional system requires special knowledge and the skills of advocacy and compassion. The purpose of this article is to discuss strategies to provide compassionate, sensitive, and trauma-informed care that demonstrates the love of Christ to incarcerated pregnant women.
Designing a Short-Term Healthcare Service-Learning Mission Trip for Impact and Sustainability
Authors: Adam Jamie , Greene Elisa
Published: June 2021

Educators creating healthcare service-learning mission trips for students recognize that success is measured in benefit to students, the community served, and in sustainability. Partnering in Guatemala with a nonprofit ministry, Belmont University faculty describe their experience with service-learning trips and how impact was measured, particularly on students' faith and service. Useful steps for overcoming barriers to sustainability for the university and local community served are provided.
Surgical Treatment of Abdominal Wall Neuromas
Authors: Chappell Ava G. , Yang Christopher S. , Dumanian Gregory A.
Published: June 2021

Background:

Neuromas are an under-recognized contributor to chronic abdominal pain. Other than after mesh inguinal hernia repair, surgical management of painful abdominal wall neuromas has not been well established in the literature.

Methods:

All patients who underwent surgical treatment for painful abdominal wall neuromas by the senior author at Northwestern Memorial Hospital were reviewed. Patients were treated with neuroma excision and allograft nerve reconstruction and/or with targeted muscle reinnervation (TMR). Follow-up pain surveys were issued to assess pain levels, activities of daily living, and pain medication usage.

Results:

Twenty patients met inclusion criteria. Eighteen (90%) patients reported improvement in neuropathic pain postoperatively. Two (10%) patients had TMR following failed nerve allograft reconstruction, which led to complete pain resolution. Twenty-seven nerves were treated surgically, the majority of which were abdominal intercostal (13), followed by ilioinguinal (10), genitofemoral (3), and iliohypogastric (1). Nerve allograft reconstruction was used alone for 18 procedures, in combination with TMR for 2, and TMR was used alone in 8. In all cases of TMR, the freshened nerve ending after neuroma excision was coapted to a motor nerve of the internal oblique. The mean length of follow-up was 18.9 months (SD ±14.5).

Conclusions:

This retrospective review demonstrated that 90% (18) of the patients had significant improvement in abdominal neuroma pain postoperatively. These results may help guide providers toward effective management of abdominal wall neuropathic pain.
Treatment for Relapsed/Refractory Acute Myeloid Leukemia
Authors: Thol Felicitas , Heuser Michael
Published: June 2021

Patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) have a poor prognosis and treatment remains challenging. For the majority of r/r patients, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment approach. Salvage therapy is given in order to reduce the leukemia load prior to transplantation. Patients achieving complete remission prior to allogeneic HSCT have a more favorable outcome. Intensive salvage regimens commonly consist of an anthracycline and high-dose cytarabine backbone. Donor lymphocyte infusions have shown efficacy in patients relapsing after allogeneic HSCT. For patients who cannot be intensively treated (eg, elderly AML patients), outcome is generally very poor and combinations with novel agents are currently under investigation. Mutational analysis should be repeated at the time of relapse to identify aberrations that can be targeted with new agents. For r/r AML patients with mutated fms-related tyrosine kinase 3 (FLT3), gilteritinib has shown superior results to intensive salvage regimens. The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved gilteritinib for FLT3 mutated r/r AML patients. Ivosidenib and enasidenib, inhibitors for mutated isocitrate dehydrogenase (IDH) 1 and 2, respectively, have received approval for IDH1/IDH2 mutated r/r AML by the FDA (not EMA). APR-246 restores the function of mutated TP53 and early study results are promising. Other agents targeting CD47, menin, neural-precursor-cell-expressed developmentally down-regulated 8, as well as bispecific antibodies or chimeric antigen receptor T cells are under investigation. Further trials are needed to understand how to best combine novel agents with each other or with chemotherapy.
Innovative Treatments for Rare Anemias
Authors: Cappellini Maria Domenica , Marcon Alessia , Fattizzo Bruno , Motta Irene
Published: June 2021

Rare anemias (RA) are mostly hereditary disorders with low prevalence and a broad spectrum of clinical severity, affecting different stages of erythropoiesis or red blood cell components. RA often remains underdiagnosed or misdiagnosed, and treatment options have been limited to supportive care for many years. During the last decades, the elucidation of the molecular mechanisms underlying several RA paved the way for developing new treatments. Innovative treatments other than supportive care and allogeneic bone marrow transplantation are currently in clinical trials for β-thalassemias, sickle cell disease (SCD), and congenital hemolytic anemias. Recently, luspatercept, an activin receptor ligand trap targeting ineffective erythropoiesis, has been approved as the first pharmacological treatment for transfusion-dependent β-thalassemia. L-glutamine, voxelotor, and crizanlizumab are new drugs approved SCD, targeting different steps of the complex pathophysiological mechanism. Gene therapy represents an innovative and encouraging strategy currently under evaluation in several RA and recently approved for β-thalassemia. Moreover, the advent of gene-editing technologies represents an additional option, mainly focused on correcting the defective gene or editing the expression of genes that regulate fetal hemoglobin synthesis. In this review, we aim to update the status of innovative treatments and the ongoing trials and discuss RA treatments’ future directions. Interestingly, several molecules that showed promising results for treating one of these disorders are now under evaluation in the others. In the near future, the management of RA will probably consist of polypharmacotherapy tailored to patients’ characteristics.
Functional Consequences of Mutations in Myeloproliferative Neoplasms
Authors: Constantinescu Stefan N. , Vainchenker William , Levy Gabriel , Papadopoulos Nicolas
Published: June 2021

Driver mutations occur in Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), and calreticulin (CALR) in BCR-ABL1 negative myeloproliferative neoplasms (MPNs). From mutations leading to one amino acid substitution in JAK2 or MPL, to frameshift mutations in CALR resulting in a protein with a different C-terminus, all the mutated proteins lead to pathologic and persistent JAK2-STAT5 activation. The most prevalent mutation, JAK2 V617F, is associated with the 3 entities polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), while CALR and MPL mutations are associated only with ET and MF. Triple negative ET and MF patients may harbor noncanonical mutations in JAK2 or MPL. One major fundamental question is whether the conformations of JAK2 V617F, MPL W515K/L/A, or CALR mutants differ from those of their wild type counterparts so that a specific treatment could target the clone carrying the mutated driver and spare physiological hematopoiesis. Of great interest, a set of epigenetic mutations can co-exist with the phenotypic driver mutations in 35%–40% of MPNs. These epigenetic mutations, such as TET2, EZH2, ASXL1, or DNMT3A mutations, promote clonal hematopoiesis and increased fitness of aged hematopoietic stem cells in both clonal hematopoiesis of indeterminate potential (CHIP) and MPNs. Importantly, the main MPN driver mutation JAK2 V617F is also associated with CHIP. Accumulation of several epigenetic and splicing mutations favors progression of MPNs to secondary acute myeloid leukemia. Another major fundamental question is how epigenetic rewiring due to these mutations interacts with persistent JAK2-STAT5 signaling. Answers to these questions are required for better therapeutic interventions aimed at preventing progression of ET and PV to MF, and transformation of these MPNs in secondary acute myeloid leukemia.
Immunomodulatory Therapies for the Treatment of Graft-versus-host Disease
Authors: Braun Lukas M. , Zeiser Robert
Published: June 2021

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative therapy for patients suffering from hematological malignancies, and its therapeutic success is based on the graft-versus-leukemia (GvL) effect. Severe acute and chronic graft-versus-host disease (GvHD) are life-threatening complications after allo-HCT. To date, most of the approved treatment strategies for GvHD rely on broadly immunosuppressive regimens, which limit the beneficial GvL effect by reducing the cytotoxicity of anti-leukemia donor T-cells. Therefore, novel therapeutic strategies that rely on immunomodulatory rather than only immunosuppressive effects could help to improve patient outcomes. Treatments should suppress severe GvHD while preserving anti-leukemia immunity. New treatment strategies include the blockade of T-cell activation via inhibition of dipeptidyl peptidase 4 and cluster of differentiation 28-mediated co-stimulation, reduction of proinflammatory interleukin (IL)-2, IL-6 and tumor necrosis factor-α signaling, as well as kinase inhibition. Janus kinase (JAK)1/2 inhibition acts directly on T-cells, but also renders antigen presenting cells more tolerogenic and blocks dendritic cell-mediated T-cell activation and proliferation. Extracorporeal photopheresis, hypomethylating agent application, and low-dose IL-2 are powerful approaches to render the immune response more tolerogenic by regulatory T-cell induction. The transfer of immunomodulatory and immunosuppressive cell populations, including mesenchymal stromal cells and regulatory T-cells, showed promising results in GvHD treatment. Novel experimental procedures are based on metabolic reprogramming of donor T-cells by reducing glycolysis, which is crucial for cytotoxic T-cell proliferation and activity.
New Developments in Diagnosis and Management of Acquired Hemophilia and Acquired von Willebrand Syndrome
Authors: Leebeek Frank W. G.
Published: June 2021

Acquired hemophilia A and acquired von Willebrand syndrome are rare, but life-threatening bleeding disorders that require prompt diagnosis and treatment by hematologists. Acquired hemophilia A is defined as an acquired severe bleeding tendency caused by autoantibody formation against coagulation factor VIII. Acquired von Willebrand syndrome is characterized by a new onset bleeding tendency caused by a reduced concentration and/or function of von Willebrand factor. These disorders are associated with a variety of underlying disorders, including various hematological malignancies, for example, plasma cell disorders, lymphoproliferative disorders, monoclonal gammopathy of undetermined significance, and myeloproliferative neoplasms. It is of utmost important to recognize these acquired bleeding disorders in these patients who are at risk for severe bleeding, and to perform additional diagnostic hemostasis laboratory evaluation. This will enable immediate diagnosis of the acquired bleeding disorder and management of both the bleeding episodes and the causative underlying disorder. In recent years, several new etiological factors for acquired hemophilia A, such as treatment with immune checkpoint inhibitors or DPP-4 inhibitors and SARS-CoV2 infection, and for acquired von Willebrand syndrome, for example, left ventricular assist devices, have been identified and also new treatment options have become available. In this concise review, the most recent data on etiology, diagnosis, and treatment of acquired bleeding disorders are presented and discussed.
Granuloma Faciale Involving the Tarsoconjunctival Surface of the Eyelid
Authors: Kolovos Antonia , Juniat Valerie , Allin Jonathan , Slattery James , Selva Dinesh
Published: June 2021

We present the case of a Caucasian woman with a histology-confirmed granuloma faciale of the tarsoconjunctival surface of the eyelid. A 66-year-old female patient presented with a 1-week history of painless left upper eyelid mass without history of allergy, trauma, or ocular surgery. There was an elevated well-demarcated flesh-colored lesion within the tarsus. Diagnosis was confirmed by history of wedge biopsy, which demonstrated a mixed inflammatory cell infiltrate on a background of fibrosis with subtle focal leucocytoclasis. The lesion was fully excised without evidence of recurrence at follow up. Granuloma faciale is a rare disease often misdiagnosed clinically. Our case report is the first-documented granuloma faciale on the tarsoconjunctival surface of the eyelid and could suggest alternative pathogenesis in granuloma faciale development. Awareness of granuloma faciale as a nonmalignant for differential for tarsal lesions is important for treating clinicians.
Association of Age-adjusted Charlson Comorbidity Index With Orbital Fungal Disease Outcomes
Authors: Kupcha Anna C. , Simmons Brittany A. , Law James J. , Liu Yuhan , Chen Qingxia , Shriver Erin M. , Brown Eric N. , Mawn Louise A.
Published: June 2021

Purpose:

To determine whether the age-adjusted Charlson comorbidity index (age-CCI) in sino-orbital fungal disease patients correlates with disease-specific mortality.

Methods:

Hospital billing systems at 2 academic institutions were queried for patients with ICD-9, ICD-10, and CPT codes used in fungal disease who also had orbital disease and significant visual loss. Thirty-two patients at Institution A and 18 patients at Institution B met the inclusion criteria of microbiologic or pathologic confirmation of fungal infection and completion of inpatient ophthalmology evaluation. Patients without radiographic abnormality in the sinus or orbit were excluded. Demographic, diagnostic, treatment, and outcome variables were recorded. Our primary outcome was death due to fungal disease.

Results:

Of the 50 medical records examined, 44 patients met the criteria for fungal-related death outcome on multivariate analysis. The regression coefficient for age-CCI and fungal-related mortality was 0.242 (95% CI, 0.012–0.779) with a p value of 0.038.

Conclusions:

Age-CCI is significantly associated with fungal-related mortality. This relationship remains significant when controlling for 5 covariates of fungal organism phylum, presence or absence of CNS disease, exenteration, local treatment use, and presence or absence of an immunosuppressive diagnosis. Age-CCI shows promise as a clinical and research tool in the evaluation of invasive fungal disease involving the orbit.
Teprotumumab and Hearing Loss: Case Series and Proposal for Audiologic Monitoring
Authors: Belinsky Irina , Creighton Francis X. , Mahoney Nicholas , Petris Carisa K. , Callahan Alison B. , Campbell Ashley A. , Kazim Michael , Lee H. B. Harold , Yoon Michael K. , Dagi Glass Lora R.
Published: June 2021

Purpose:

To present a protocol for audiologic monitoring in the setting of teprotumumab treatment of thyroid eye disease, motivated by 4 cases of significant hearing loss, and review the relevant literature.

Methods:

Cases of hearing loss in the setting of teprotumumab were retrospectively elicited as part of a multi-institutional focus group, including oculoplastic surgeons, a neurotologist and an endocrinologist. A literature review was performed.

Results:

An aggregate of 4 cases of teprotumumab-associated hearing loss documented by formal audiologic testing were identified among 3 clinicians who had treated 28 patients.

Conclusions:

Teprotumumab may cause a spectrum of potentially irreversible hearing loss ranging from mild to severe, likely resulting from the inhibition of the insulin-like growth factor-1 and the insulin-like growth factor-1 receptor pathway. Due to the novelty of teprotumumab and the lack of a comprehensive understanding of its effect on hearing, the authors endorse prospective investigations of hearing loss in the setting of teprotumumab treatment. Until the results of such studies are available, the authors think it prudent to adopt a surveillance protocol to include an audiogram and tympanometry before, during and after infusion, and when prompted by new symptoms of hearing dysfunction.
Globe Subluxation After Proning in a Coronavirus Disease 2019 Patient
Authors: Karani Rabia , Valenzuela Ives A. , Tran Ann Q. , North Victoria S. , Kazim Michael
Published: June 2021

A 79-year-old male was hospitalized for respiratory failure secondary to coronavirus disease 2019 pneumonia. Approximately 6 hours after initiating proning, left globe subluxation with darkening of the superior sclera consistent with tache noir was noted. The left globe was thought to be hypotonus secondary to ciliary body shut down after a prolonged period of high intraocular pressure. The globe was reduced in the supine position with gentle traction of the eyelids. Over the next 24 hours, the left intraocular pressure improved to 10 mm Hg, and the tache-noir de la sclérotique resolved. The authors report the first known case of globe subluxation secondary to proning.
Central Processing in Tinnitus: fMRI Study Outlining Patterns of Activation Using an Auditory Discrimination Task in Normal Versus Tinnitus Patients
Authors: Zenke Julianna K. , Rahman Samiha , Guo Qi , Leung Ada W. S. , Gomaa Nahla A.
Published: June 2021

Objective:

Elucidate brain activity differences between patients with tinnitus and controls.

Study Design:

Cross-sectional cohort study.

Setting:

Outpatient Otolaryngology clinic.

Patients:

Three cohorts; 8 controls, 12 with subjective idiopathic tinnitus (tinnitus without hearing loss), and 12 with both tinnitus and hearing loss.

Intervention:

An auditory oddball identification task was performed in fMRI scanner.

Main Outcome Measures:

Task performance and Tinnitus Handicap Inventory (THI) scores were recorded. Brain activation maps were generated comparing deviant and standard tones as well as at rest. One-way and two-way T-contrasts were generated in addition to multiple regression modeling which identified significant brain regions predicting tinnitus, disease severity, duration, and task performance.

Results:

Task performance worsened in tinnitus patients with increased auditory workload, in terms of additional hearing loss. THI score and grade correlated with false alarms. The limbic system, heschel's gyrus, angular gyrus and cerebellum have a significant effect on both brain behavior in patients with tinnitus, and predictability of tinnitus and its behavioral implications.

Conclusion:

Increased auditory workload resulted in poorer task performance. Moreover, it is possible to predict auditory task performance in patients with tinnitus by looking at the activity of specific regions of interest. Heschl's gyrus, angular gyrus, cerebellar, and limbic system activity are important contributors to neurological activity associated with tinnitus. Finally, predictive modeling may influence further research surrounding tinnitus treatment.
Whole blood hemostatic resuscitation in pediatric trauma: A nationwide propensity-matched analysis
Authors: Anand Tanya , Obaid Omar , Nelson Adam , Chehab Mohamad , Ditillo Michael , Hammad Ahmad , Douglas Molly , Bible Letitia , Joseph Bellal
Published: June 2021

BACKGROUND

Whole blood (WB) has shown promise in pediatric trauma resuscitation following its prominent role in the resuscitation of adult trauma patients. Although WB in children has been shown to be feasible, its effectiveness has yet to be explored. The aim of this study was to examine the outcomes of WB transfusion as an adjunct to component therapy (CT) compared with CT only as early resuscitation for pediatric trauma patients.

METHODS

Children aged 1 to 17 years, who were transfused within 4 hours of presentation, were identified in the Trauma Quality Improvement Program 2017 database. Patients were stratified into those receiving WB-CT versus CT alone. Propensity score matching in a 1:2 ratio was performed based on patient demographics, injury characteristics, hemorrhage control interventions, and trauma center level. The primary outcome measure was patient transfusion requirement. Secondary outcome measures were mortality, hospital length of stay, ventilation days, and major complications.

RESULTS

A total of 135 children receiving WB-CT were matched to 270 patients receiving CT only. Mean (SD) age was 12 (5) years, 66% were male, and the median Injury Severity Score was 32 (range, 20–43). A total of 51% of patients were in shock, 34% had penetrating injuries, and 41% required surgical intervention for hemorrhage control. Total blood products transfused were significantly decreased in children receiving WB, both at 4 hours (35 [22–73] vs. 48 [33–95] mL/kg; p = 0.013) and 24 hours (39 [24–97] vs. 53 [36–119] mL/kg; p < 0.001). Mortality rate at 24 hours (19.3% vs. 21.9%; p = 0.546) and in-hospital mortality (31.1% vs. 34.4%; p = 0.502) were not different. Similarly, no difference in hospital length of stay and rates of major complications was found. Patients in the WB group required significantly less ventilation days (2 [2–6] vs. 3 [2–8] days; p = 0.021).

CONCLUSION

Using WB as an adjunct to CT was associated with decreased transfusion requirements and ventilation days in pediatric trauma patients.

LEVEL OF EVIDENCE

Therapeutic, level III.
Evaluation of statewide utilization of helicopter emergency medical services for interfacility transfer
Authors: Udekwu Pascal , Stiles Anquonette , Tann Kimberly , McIntyre Sarah , Roy Sara , Schiro Sharon
Published: June 2021

BACKGROUND

Helicopter emergency medical services (HEMSs) are used with increasing frequency for the transportation of injured patients from the scene and from treatment facilities to higher levels of care. Improved outcomes have been difficult to establish, and reports of overutilization and financial harm have been published. Our study was performed to evaluate statewide utilization for interfacility transfers (IFTs).

METHODS

Data from the North Carolina state trauma registry from 2013 to 2017 were evaluated and ground, and helicopter IFTs were compared.

RESULTS

Overall interfacility use of HEMSs peaked at 7,861 patient transports in 2016, and the percent of all IFTs fell from 17% to 13.3% over the study period. Helicopter emergency medical services patients were more likely to be male (69.8%) and younger (48.0 vs. 56.2 years), and have higher Injury Severity Scores (14.6 vs. 9.0) and higher mortality (10.5% vs. 2.8%) than ground emergency medical services (GEMSs) patients. When adjusted for age, sex, Injury Severity Score, and transport distance, HEMSs survival was significantly higher (odds ratio, 0.353; 95% CI, 0.308–0.404; p < 0.0001). Normal prehospital vital signs (VSs) and Glasgow Coma Scale score motor component (GCS-M) were associated with low mortality rates in both groups. Abnormal prehospital VSs and GCS-M were associated with an 11.8% mortality rate in HEMSs patients and 3.1% in GEMSs patients. Normal referring facility VSs and GCS-M did not confer similar protection with a mortality rate of 10.0% in HEMSs patients and 2.8% in GEMSs. Changes in prehospital to referring facility VSs did not demonstrate a low mortality group. Abbreviated Injury Scale and changes in VSs did not identify HEMSs transport benefit groups.

CONCLUSION

The proportion of HEMSs transfers fell over the study period and, while associated with a 10.5% mortality rate, had an outcome benefit compared with GEMSs. These patients could not be sorted into risk categories for transportation choice based on VSs or GCS-M derangement or by changes thereof, and opportunities for system improvement were not identified.

LEVEL OF EVIDENCE

Prognostic/epidemiological study, level III; Care Management, level IV.
Opportunities and challenges when using record linkage of routinely collected electronic health care data to evaluate outcomes of systemic anti-cancer treatment in clinical practice
Authors: Mueller Tanja , Laskey Jennifer , Baillie Kelly , Clarke Julie , Crearie Christine , Kavanagh Kimberley , Graham Janet , Graham Kathryn , Waterson Ashita , Jones Robert , Kurdi Amanj , Morrison David , Bennie Marion
Published: June 2021

Objectives

To discuss the opportunities and challenges when applying an electronic record linkage methodology with respect to systemic anti-cancer therapy, and to highlight some of the potential pitfalls spanning the entire breadth and depth of the research process.

Design

Retrospective cohort studies using routinely collected, administrative health data. Setting: Scotland

Results

Studies conducted to-date have indicated that record linkage of routinely collected data to determine outcomes of treatment with cancer medicines is feasible, albeit currently within certain limits. While the general description of patient populations and the calculation of median overall survival are well supported, prevailing issues with combining data across regional boundaries and the limited availability of some variables (including molecular pathology data and information regarding toxicities) may restrict the extent of analyses feasible.

Conclusion

There is scope to conduct large cohort studies to generate results from clinical practice using linkage of routinely collected health care data within a reasonable time frame; however, close collaboration between researchers, data controllers, and clinicians is required in order to obtain valid and meaningful results.

Article Summary

Strengths and limitations of this study

This is the first description of a comprehensive programme aimed at evaluating the feasibility of linking routinely collected health data to evaluate the outcomes of systemic anti-cancer treatment in clinical practice.

The multi-disciplinary study team comprised both academics and clinicians, with a wide range of skills, expertise, and experience.

While a number of studies focusing on different cancers have successfully been conducted, not all research questions of interest could be fully answered due to some existing data gaps.

Nevertheless, study findings have been discussed with health care professionals across Scotland, and have started to have an impact on shared patient-clinical decision making.
Genomic analyses in a large clinical cohort reveal high prevalence of MECP2 variants associated with neuropsychiatric phenotypes in adulthood
Authors: Gonzaga-Jauregui Claudia , Kurolap Alina , Walsh Lauren , Staples Jeffrey , Van Hout Cristopher , Oetjens Matthew , Liu Daren ,   Regeneron Genetics Center, Samaco Rodney , Weiss Karin , Feldman Hagit Baris , Martin Christa L.
Published: June 2021

This manuscript has been withdrawn as it was submitted without full consent of all the authors.
Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder
Authors: Mattioli Francesca , Darvish Hossein , Paracha Sohail Aziz , Tafakhori Abbas , Firouzabadi Saghar Ghasemi , Chapi Marjan , Azhar Baig Hafiz Muhammad , Reymond Alexandre , Antonarakis Stylianos E. , Ansar Muhammad
Published: June 2021

Intellectual disability (ID) is a highly heterogeneous disorder with hundreds of associated genes. Despite progress in the identification of the genetic causes of ID following the introduction of high-throughput sequencing, about half of affected individuals still remain without a molecular diagnosis. Consanguineous families with affected individuals provide a unique opportunity to identify novel recessive causative genes.

In this report we describe a novel autosomal recessive neurodevelopmental disorder. We identified two consanguineous families with homozygous variants predicted to alter the splicing of ATP9A which encodes a transmembrane lipid flippase of the class II P4-ATPases. The three individuals homozygous for these putatively truncating variants presented with severe ID, motor and speech impairment, and behavioral anomalies. Consistent with a causative role of ATP9A in these patients, a previously described Atp9a-/-mouse model showed behavioral changes.
Association between motor task acquisition and hippocampal atrophy across cognitively unimpaired, amnestic Mild Cognitive Impairment, and Alzheimer’s disease individuals
Authors: Schaefer Sydney Y. , Malek-Ahmadi Michael , Hooyman Andrew , King Jace B. , Duff Kevin
Published: June 2021

Hippocampal atrophy is a widely used biomarker for Alzheimer’s disease (AD), but the cost, time, and contraindications associated with magnetic resonance imaging (MRI) limit its use. Recent work has shown that a low-cost upper extremity motor task has potential in identifying AD risk. Fifty-four older adults (15 cognitively unimpaired, 24 amnestic Mild Cognitive Impairment, and 15 AD) completed six motor task trials and a structural MRI. Motor task acquisition significantly predicted bilateral hippocampal volume, controlling for age, sex, education, and memory. Thus, this motor task may be an affordable, non-invasive screen for AD risk and progression.
Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 and ALYREF as new candidate risk genes
Authors: Qiao Lu , Xu Le , Yu Lan , Wynn Julia , Hernan Rebecca , Zhou Xueya , Farkouh-Karoleski Christiana , Krishnan Usha S. , Khlevner Julie , De Aliva , Zygmunt Annette , Crombleholme Timothy , Lim Foong-Yen , Needelman Howard , Cusick Robert A. , Mychaliska George B. , Warner Brad W. , Wagner Amy J. , Danko Melissa E. , Chung Dai , Potoka Douglas , Kosiński Przemyslaw , McCulley David J. , Elfiky Mahmoud , Azarow Kenneth , Fialkowski Elizabeth , Schindel David , Soffer Samuel Z. , Lyon Jane B. , Zalieckas Jill M. , Vardarajan Badri N. , Aspelund Gudrun , Duron Vincent P. , High Frances A. , Sun Xin , Donahoe Patricia K. , Shen Yufeng , Chung Wendy K.
Published: June 2021

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (Lon Peptidase 1, Mitochondrial) and ALYREF (Aly/REF Export Factor) as novel candidate CDH genes based on de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 cases and 11,220 ancestry-matched population controls and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in familial cases. Approximately 3% of our CDH cohort was heterozygous with ultra-rare predicted damaging variants in LONP1 who have a range of clinical phenotypes including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium specific deletion of Lonp1 die immediately after birth and have reduced lung growth and branching that may at least partially explain the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.
Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19
Authors: Wang Junzheng , Levi Jacob , Ellis Leah , Hill Andrew
Published: June 2021

Background

Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. Safe and effective treatments will need to be both affordable and widely available globally to be used alongside vaccination programmes. This analysis will estimate and compare potential generic minimum costs of a selection of approved COVID-19 drug candidates with available international list prices.

Methods

We searched for repurposed drugs that have been approved by at least one of the WHO, FDA or NICE, or at least given emergency use authorisation or recommended for off-label prescription. Drug prices were searched for, for dexamethasone, budesonide, baricitinib, tocilizumab, casirivimab and imdevimab, and sarilumab using active pharmaceutical ingredients (API) data extracted from global shipping records. This was compared with national pricing data from a range of low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug.

Results

Repurposed therapies can be generically manufactured for some treatments at very low per-course costs, ranging from $2.58 for IV dexamethasone (or $0.19 orally) and $4.34 for inhaled budesonide. No export price data was available for baricitinib, tocilizumab, casirivimab and imdevimab or sarilumab, but courses of these treatments are priced highly, ranging from $6.67 for baricitinib to $875.5 for sarilumab. When comparing international list prices, we found wide variations between countries.

Conclusions

Successful management of COVID-19 will require equitable access to treatment for all populations, not just those able to pay high prices. Dexamethasone and budesonide are widely available and affordable, whilst monoclonal antibodies and IV treatment courses are more expensive.

Key Points

Re-purposed drugs must be affordable worldwide to compliment COVID-19 vaccine programmes.

Estimated costs/course were: dexamethasone (Oral $0.22, IV $2.58), budesonide ($4.34), baricitnib ($6.67), tocilizumab ($410.59), sarilumab ($875.70). Casirivimab and imdevimab = no data available.

High drug prices will limit access.
Insecticide resistance outpaces behavioural adaptation, as a response to Long-Lasting Insecticidal Net distribution, in malaria vectors in Burkina Faso
Authors: Sanou Antoine , Nelli Luca , Guelbéogo W. Moussa , Cissé Fatoumata , Tapsoba Michel M. , Ouédraogo Pierre , Sagnon N’falé , Ranson Hilary , Matthiopoulos Jason , Ferguson Heather M.
Published: June 2021

The decline in malaria across Africa has been largely attributed to vector control using Long-Lasting Insecticidal Nets (LLINs). However, this intervention has prompted widespread insecticide resistance (IR) and been associated with changes in mosquito behaviour that reduce their contact with LLINs. The relative importance and rate at which IR and behavioural adaptations emerge are poorly understood. We conducted surveillance of mosquito behaviour and IR at 12 sites in Burkina Faso to assess the magnitude and temporal dynamics of insecticide and behavioural resistance in vectors in the 2-year following mass LLIN distribution. Insecticide resistance was present in all vector populations and increased rapidly over the study. In contrast, no longitudinal shifts in LLIN-avoidance behaviours (earlier or outdoor biting and resting) were detected. There was a moderate shift in vector species composition fromAnopheles coluzziitoAnopheles gambiaewhich coincided with a reduction in the proportion of bites preventable by LLINs; possibly driven by between-species variation in behaviour. These findings indicate that adaptations based on insecticide resistance arise and intensify more rapidly than behavioural shifts within mosquito vectors. However, longitudinal shifts in mosquito vector species composition were evident within 2 years following a mass LLIN distribution. This ecological shift was characterized by a relative increase in the moderately more exophagic species (An. gambiae) and coincided with a predicted decline in the degree of protection expected from LLINs. Although human exposure fell through the study period due to reducing vector densities and infection rates, such ecological shifts in vector species along with insecticide resistance were likely to have eroded the efficacy of LLINs. While both adaptations impact malaria control, the rapid increase of the former indicates it is the most rapid strategy but interventions targeting both will be needed.
Why is non-suicidal self-injury more prevalent among women? Mediation and moderation analyses of psychological distress, emotion dysregulation, and impulsivity
Authors: Lutz Nina M. , Neufeld Sharon A.S. , Hook Roxanne W. , Jones Peter B. , Bullmore Ed T. , Goodyer Ian M. , Chamberlain Samuel R. , Wilkinson Paul O.
Published: June 2021

Objective

Non-suicidal self-injury (NSSI) appears to be more common among women than men, though the underlying reasons for this remain unclear. In a community sample of young adults (n=996, aged 18-30) assessed during the COVID-19 pandemic, we investigated gendered patterns in NSSI etiology.

Methods

Mediation and moderation analyses considered associations between past-year NSSI prevalence, gender, and putative mechanistic variables: self-reported psychological distress (K10), emotion dysregulation (DERS), and impulsivity (UPPS-P).

Results

Nearly twice as many women as men reported past-year NSSI (14.47% versus 7.78%). Women reported significantly higher psychological distress and significantly lower sensation seeking and positive urgency than men. Psychological distress partially statistically mediated the relationship between gender and past-year NSSI. Gender did not significantly moderate associations between self-reported distress, emotion dysregulation, or impulsivity and past-year NSSI. Past-year NSSI prevalence did not significantly decrease with age and we found no significant age by gender interaction.

Conclusions

Greater levels of NSSI in young women are explained by their greater levels of emotional distress. Women do not appear to be more likely than men to report NSSI due to differences in how they manage emotional distress: gender did not moderate the association between psychological distress and past-year NSSI, and there were no gender differences in emotion dysregulation or negative urgency. Furthermore, we show that NSSI remains prevalent beyond adolescence. Early interventions which reduce distress or improve distress tolerance, strengthen emotion regulation skills, and provide alternative coping strategies merit investigation for NSSI.

Highlights

Young women were significantly more likely to report past-year NSSI than young men

Psychological distress partially mediated the relationship between gender and NSSI

Gender did not moderate associations between putative mechanistic variables and NSSI