bluuebunny/crossref_metadata_2025 huggingface dataset:
Epacadostat Plus Pembrolizumab and Chemotherapy for Advanced Solid Tumors: Results from the Phase I/II ECHO-207/KEYNOTE-723 Study
Authors: Powderly John D , Klempner Samuel J , Naing Aung , Bendell Johanna , Garrido-Laguna Ignacio , Catenacci Daniel V T , Taylor Matthew H , Lee James J , Zheng Fred , Zhou Feng , Gong Xiaohua , Gowda Hema , Beatty Gregory L
Published: September 2022

Background

Epacadostat, an oral, selective inhibitor of IDO1, has shown activity when administered with pembrolizumab. We evaluated the addition of chemotherapy to epacadostat and pembrolizumab in patients with advanced or metastatic solid tumors. One proposed mechanism of resistance to PD-1 checkpoint inhibition is through immunosuppression mediated by L-kynurenine. IDO1, indoleamine-2,3-dioxygenase 1 is the rate-limiting enzyme catalyzing the conversion of L-tryptophan to L-kynurenine. If IDO1 is a mechanism of tumor escape from checkpoint inhibition, then addition of an IDO1 inhibitor with a PD-1 checkpoint inhibitor could enable tumor response to immunotherapy.

Methods

Patients received one of 7 tumor-appropriate chemotherapy regimens. Pembrolizumab 200 mg was infused intravenously every 3 weeks. Epacadostat 100 mg was administered orally twice daily. The primary objectives of phase I were determining safety/tolerability and defining the maximum tolerated or pharmacologically active dose of epacadostat. Phase II of the study was designed to enroll efficacy-expansion cohorts and to assess changes in the tumor and tumor microenvironment via mandatory-biopsy cohorts.

Results

A total of 70 patients were enrolled. Twelve patients were enrolled in the phase II mandatory-biopsy cohorts. Due to early study closure, efficacy expansion did not enroll. Grades 3 and 4 treatment-emergent adverse events (TEAEs) occurred in 78.6% of patients. Neutropenia and disease progression were the only grades 3 and 4 TEAEs reported in ≥10.0% of patients. One treatment-related death was reported. The ORR was 31.4% across all treatment groups.

Conclusion

The combination of epacadostat 100 mg bid with pembrolizumab and chemotherapy had an acceptable safety profile. This regimen showed antitumor activity across multiple types of advanced or metastatic solid tumors (ClinicalTrials.gov Identifier: NCT03085914).
Through an Australian Lens: Exploring the Impact of Body-Worn Cameras on Police–Community Relations
Authors: Davies Amanda
Published: September 2022

As the police and law enforcement community globally continue to increase the implementation of body-worn cameras (BWCs), there is a building body of knowledge as to the advantages and disadvantages of this tool for policing. Corresponding to the more widespread use of BWCs by police officers is an increase in the areas and level of scrutiny that are caught in the cascading impact of their use. One of the much-lauded potential benefits for the BWCs was the expectation of building positive relationships between officers and the citizens of the community they police. This paper presents findings from a comprehensive research evaluation of the Australian New South Wales Police Force BWC initiative. The findings from the study related to understanding the perspective of the impact of BWCs on the relationship between community members and police officers are presented and discussed. The findings indicate a high level of optimism and positive experience with the impact of the use of BWCs, specifically as it relates to change of behaviour and transparency and accountability of police and members of the public. The study offers a contribution to understanding the role of BWCs in progressing police legitimacy, from both the public and police perspectives in a 21st-century democratic society.
Reproductive Development of Male Rats Exposed In Utero to Stress and/or Sertraline
Authors: Quiarato Lozano Ana Flávia , Marques Tavares Bruna , Villela e Silva Patrícia , Franco de Barros Jorge Willian , De Grava Kempinas Wilma
Published: September 2022

Despite increased prescription of sertraline during pregnancy, little is known about its action on reproductive development. Therefore, this study aimed to investigate the impact that stress, associated or not with sertraline, causes on the reproductive development of male rats. Pregnant Wistar rats were divided into 4 groups (n = 16/group): CO—received filtered water; SE—received 20 mg/kg sertraline; ST—submitted to restraint stress and received filtered water; SS—submitted to restraint stress and received sertraline. The treatment was carried out from gestational days (GDs) 13–20. The animals were euthanized on GD 20 (n = 8/group), postnatal day (PND) 45 (n = 8/group), and PND 110 (n = 8/group). The testes and epididymis were analyzed histologically, and immunohistochemistry was performed on the testes by proliferating cell nuclear antigen (PCNA) and the Wilms tumor protein (Wt1). Sperm quality was also analyzed on PND 110. The evolution of body weight, anogenital distance (AGD), and puberty installation day were also verified. Statistical analysis: 2-way ANOVA or Kruskal-Wallis test (p ≤ .05). Fetal testes presented a large number of acidophilic cells in the sertraline-exposed groups. The SS group also showed a decrease in the nuclear volume of Leydig cells. This same group showed low expression of PCNA and Wt1, decreased weight of the testes and epididymis, lower AGD, and delayed puberty installation. The adulthood groups exposed to sertraline presented alterations in sperm morphology and motility. The results demonstrated that prenatal exposure to sertraline compromises the development of the rat reproductive system.
Pain treatment and prophylaxis on pain
Authors: Raeder Johan
Published: September 2022

Purpose of review

Also in ambulatory surgery, there will usually be a need for analgesic medication to deal with postoperative pain. Even so, a significant proportion of ambulatory surgery patients have unacceptable postoperative pain, and there is a need for better education in how to provide proper prophylaxis and treatment.

Recent findings

Postoperative pain should be addressed both pre, intra- and postoperatively. The management should be with a multimodal nonopioid-based procedure specific guideline for the routine cases. In 10–20% of cases, there will be a need to adjust and supplement the basic guideline with extra analgesic measures. This may be because there are contraindications for a drug in the guideline, the procedure is more extensive than usual or the patient has extra risk factors for strong postoperative pain. Opioids should only be used when needed on top of multimodal nonopioid prophylaxis. Opioids should be with nondepot formulations, titrated to effect in the postoperative care unit and eventually continued only when needed for a few days at maximum.

Multimodal analgesia should start pre or per-operatively and include paracetamol, nonsteroidal anti-inflammatory drug (NSAID), dexamethasone (or alternative glucocorticoid) and local anaesthetic wound infiltration, unless contraindicated in the individual case. Paracetamol and NSAID should be continued postoperatively, supplemented with opioid on top as needed. Extra analgesia may be considered when appropriate and needed. First-line options include nerve blocks or interfascial plane blocks and i.v. lidocaine infusion. In addition, gabapentinnoids, dexmedetomidine, ketamine infusion and clonidine may be used, but adverse effects of sedation, dizziness and hypotension must be carefully considered in the ambulatory setting.
Transitioning From High-dose Methadone to Buprenorphine Using a Microdosing Approach: Unique Considerations at ASAM Level 3 Facilities
Authors: Anderson Carolyn , Cooley Rachel , Patil Dustin
Published: September 2022

Transitions from high-dose methadone to buprenorphine for treatment of opioid use disorder (OUD) present risk of precipitated withdrawal related to the introduction of a high-affinity partial agonist at the mu-opioid receptor after occupancy by a lower-affinity full agonist. Various strategies have been explored to maintain patient stability during this process, including microdosing buprenorphine. Current literature lacks consensus on an optimal setting and strategy for initiating a buprenorphine microdosing protocol and gives little detail on patients’ conditions after the acute transition period. We report a 6-day microdosing transition from methadone 100 mg directly to sublingual buprenorphine, followed by a 20-day period of monitoring and additional treatment. This patient tolerated a sublingual buprenorphine microdosing protocol while using supportive medications with a peak Clinical Opiate Withdrawal Scale score of 6. The patient’s most significant withdrawal symptoms occurred several days after completion of the microdosing process. This case demonstrates the feasibility of using a transmucosal buprenorphine formulation in microdosing transitions from high-dose methadone directly to buprenorphine, and highlights the utility of a medically monitored intensive inpatient setting (American Society of Addiction Medicine level 3.7) in providing appropriate monitoring and treatment during and after a microdosing transition.
Feasibility Pilot Study of an Opioid Helpline for Individuals at High Risk for Opioid Use Disorder
Authors: Ait-Daoud Tiouririne Nassima , Coley Justin , Kalelioglu Tevfik , Schorling Kelly
Published: September 2022

Background

Evidence suggests that educational interventions delivered by healthcare providers can be effective in altering patients’ attitudes toward pain management and in referral to addiction treatment when appropriate. Time constraints during visits limit the delivery of such important interventions.

Objective

This study aims to explore the feasibility and perceived value of an opioid helpline that provides resources to individuals suffering from or at risk for opioid use disorder.

Methods

We developed a helpline with a toll-free number “1-877 OPIOIDS (6437)” established through the University of Virginia, which runs Monday through Friday from 8:30 am to 5 pm and is answered by a live answering service after hours. The helpline offered a range of resources including opioid pain medication education, signs of overdose or withdrawal, addiction treatment options, and connection to treatment services. The helpline was supported by outreach efforts to surrounding counties in Virginia. Questionnaires on perceived usefulness were sent to callers and providers who used or offered the helpline in their clinics. Survey data were analyzed to identify trends.

Results

Thirty-one consented individuals of 166 contacts were included in the study. Although participants were referred to the helpline through a variety of sources, most were referred by a physician (38.7%). Most participants rated the helpline’s helpfulness with the highest satisfaction score (81.5%). Most individuals seeking addiction treatment found the helpline to be useful, whereas those referred by their respective physician to gain more information about their opioid use and prevent escalation to addiction felt it was an unnecessary step.

Conclusions

Our pilot study demonstrated that a helpline could be an additional tool to combat the opioid crisis. Individual callers rated the intervention favorably. Our study shows that the most substantial area of satisfaction for our participants is being able to reach a live person when in need.
Regulation of Innate and Adaptive Immunity using Herbal Medicine: Benefits for the COVID-19 Vaccination
Authors: Li Xuan , Wichai Nuttapong , Wang Jiabao , Liu Xiuping , Yan Huimin , Wang Yu , Luo Mingchi , Zhou Shengyuan , Wang Kai , Li Lin , Miao Lin
Published: September 2022

Vaccination is a major achievement that has become an effective prevention strategy against infectious diseases and active control of emerging pathogens worldwide. In response to the coronavirus disease 2019 (COVID-19) pandemic, several diverse vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and deployed for use in a large number of individuals, and have been reported to protect against symptomatic COVID-19 cases and deaths. However, the application of vaccines has a series of limitations, including protective failure for variants of concern, unavailability of individuals due to immune deficiency, and the disappearance of immune protection for increasing infections in vaccinated individuals. These aspects raise the question of how to modulate the immune system that contributes to the COVID-19 vaccine protective effects. Herbal medicines are widely used for their immune regulatory abilities in clinics. More attractively, herbal medicines have been well accepted for their positive role in the COVID-19 prevention and suppression through regulation of the immune system. This review presents a brief overview of the strategy of COVID-19 vaccination and the response of the immune system to vaccines, the regulatory effects and mechanisms of herbal medicine in immune-related macrophages, natural killer (NK) cells, dendritic cells (DCs), and lymphocytes T and B cells, and how they help vaccines work. Later is the article, the potential role and application of herbal medicines in the most recent COVID-19 vaccination are discussed. This article provides new insights into herbal medicines as promising alternative supplements that may benefit from COVID-19 vaccination.
CLINICAL IMPLICATION OF RETINAL NERVE FIBER LAYER SCHISIS AND MACULAR FLUORESCEIN LEAKAGE IN PRIMARY IDIOPATHIC EPIRETINAL MEMBRANE
Authors: Kim Jonghyun , Kim Seong-Woo , Choi Mihyun , Yun Cheolmin , Oh Jaeryung
Published: September 2022

Purpose:

We evaluated the relationship between macular fluorescein leakage and retinal nerve fiber layer (RNFL) schisis and investigated the visual prognostic values after pars plana vitrectomy (PPV) and idiopathic epiretinal membrane removal.

Methods:

We analyzed the correlations between preoperative optical coherence tomography (OCT) parameters and macular leakage. The final best-corrected visual acuity and central macular thickness were compared according to the presence or absence of macular leakage and RNFL schisis.

Results:

In 80 eyes with idiopathic epiretinal membrane treated with PPV and membrane peeling, preoperative macular leakage was associated with the presence of preoperative RNFL schisis and inner nuclear layer microcysts. Eyes with both macular leakage and RNFL schisis showed worse postoperative best-corrected visual acuity than those without both factors.

Conclusion:

In the presence of macular fluorescein leakage and RNFL schisis, postoperative best-corrected visual acuity is worse, and improvements in the central macular thickness are greater than those in the absence of both factors.
FOCAL CHOROIDAL THICKNESS HEMODYNAMICS AS a SIGN OF MACULAR NEOVASCULARIZATION ACTIVITY IN PATHOLOGIC MYOPIA
Authors: Amoroso Francesca , Miere Alexandra , El Matri Khaled , Cohen Salomon Yves , Jung Camille , Pallone Carlotta , Bruyere Elsa , El Matri Leila , Souied Eric H.
Published: September 2022

Purpose:

To analyze the relationship between a focal increase of choroidal thickness (ChT) and exudative activity of macular neovascularization (MNV) secondary to pathologic myopia.

Methods:

Retrospective analysis including eyes with pathologic myopia presenting with a focally increased ChT underneath active MNV. All patients included were treated, and ChT was measured before and after each intravitreal injection by two experienced ophthalmologists.

Results:

Fifty-two eyes of 52 patients with myopic MNV (19 men and 33 women) were included in this analysis. ChT at T-1 averaged 51.09 ± 33.56 μm, whereas at the time of MNV activation (T0), ChT was significantly thicker: 85.11 ± 43.99 μm (P < 0.001). After a single intravitreal injection, the ChT significantly decreased to 53.23 ± 34.15 μm (P < 0.001).

Conclusion:

This study showed that focal ChT variations may be considered an interesting corollary sign of MNV in high myopic patients, indicating the activity of myopic neovascularization.
Peoples' beliefs about their chronic hip pain and its care: a systematic review of qualitative studies. “I'm just getting old and breaking down”
Authors: Haber Travis , Hinman Rana S. , Dobson Fiona , Bunzli Samantha , Hilton Adam , Hall Michelle
Published: September 2022

To enhance patient-centred care of people with hip pain, we need a comprehensive understanding of peoples' beliefs about their hip pain. This systematic review explored the beliefs and expectations of middle-aged and older adults about chronic hip pain and its care across different healthcare settings and contexts. This review was a synthesis of qualitative studies using a framework synthesis approach. We searched 5 databases: MEDLINE, CINAHL, The Cochrane Central Register of Controlled Trials, EMBASE, and PsycINFO. Two reviewers independently screened the studies for eligibility. We included qualitative studies that included people with a mean age of older than 45 years and 80% or more of the participants had chronic hip pain, or if they reported the data about participants with chronic hip pain who were 45 years or older separately. We excluded studies of people with systemic conditions and studies not published in English. We included 28 studies involving 352 participants with chronic hip pain. We generated 5 themes: (1) biomedical causes (subtheme 1: scary pathoanatomical labels, subtheme 2: information needs); (2) negative impacts on physical, social, and mental health; (3) activity avoidance or modification and rest; (4) treatment failures (subtheme: information and support were helpful); (5) surgery is inevitable. Middle-aged and older adults labelled their hip joint damaged and attributed their hip pain to age, and wear and tear. People coped with their hip pain by avoiding or modifying activity. People were not educated about treatments or used treatments that failed to improve their hip pain. People believed that surgery for their hip was inevitable.
Early Insights From a Pharmacogenomic-Enriched Comprehensive Medication Management Program Implementation in an Adult Employee Population
Authors: Keogh Murray , Fragala Maren S. , Peter Arul Prakasam , Lorenz Raymond A. , Goldberg Steven E. , Shaman Jeffrey A.
Published: September 2022

Objectives

The aims of the study are to assess adoption of a pharmacogenomic-enriched comprehensive medication management program in a self-insured employer setting and to better understand medication risks that affect employees.

Methods

Employees were identified to be at high risk of medication mismanagement and were subsequently provided with a program and process to improve their health. DNA testing, a clinical decision support system, and pharmacists were used to identify medication safety and effectiveness issues and to recommend appropriate changes.

Results

A total of 10.6% of the invited employees enrolled in the program. Actionable recommendations were suggested by pharmacists for 85.8% of employees who completed the program, averaging 5.2 recommendations per person.

Conclusions

Implementation of a PGx + CMM program in a self-insured employer setting is feasible, detects risks in prescription regimens, and offers opportunities to improve medication management and reduce the burden of healthcare expenses.
Clinical Outcomes after One-day or Two-day Intervals in Conditioning Regimens for allo-HCT
Authors: Matsushima Satoru , Kobayashi Ryoji , Sano Hirozumi , Hori Daiki , Yanagi Masato , Kobayashi Kunihiko
Published: September 2022

One-day or two-day intervals are generally inserted into scheduled conditioning regimens for allogeneic hematopoietic cell transplantation, primarily due to various social circumstances, such as unexpected natural adversities, abrupt deterioration of patient health, and delays in graft source arrival. We compared the clinical outcomes of patients with interrupted conditioning with those with ordinarily scheduled conditioning. We analyzed 83 patients (children and adolescents) with oncologic disease who underwent myeloablative conditioning with total body irradiation. Overall and event-free survival were similar between the groups (P=0.955, P=0.908, respectively). Non-relapse mortality and relapse rates were similar between the groups (P=0.923, P=0.946, respectively). The engraftment rate was not affected by interruption (P=1.000). In contrast, the incidence of chronic graft-versus-host disease (GVHD) was higher in the interrupted group compared with the scheduled group, although there was no statistical significance (42% vs. 19%, P=0.063). Conditioning interruption was identified to be an independent risk factor for chronic GVHD by multivariate analysis (odds ratio: 3.72; 95% CI: 1.04 to 13.3; P=0.043). In conclusion, apart from the incidence of chronic GVHD, clinical outcomes were not affected by one-day or two-day intervals during conditioning.
Ruxolitinib in a Child With JAK2 Exon 12 Mutant Polycythemia Vera
Authors: Stoops Katie , Kuril Sandeepkumar
Published: September 2022

Background:

Polycythemia Vera (PV) is a well-defined disorder of erythroid hyperproliferation that can result in life-threatening thromboembolic and hemorrhagic events. It is most prevalent in adults and is caused by mutations in Janus Kinase 2 (JAK2). Predominantly, PV is caused by a JAK2V617F mutation on exon 14.

Observations:

A rare case of PV in a 9-year-old, driven by an uncommon, p.Glu543_Asp544del, JAK2 exon 12 mutation. Despite management with phlebotomy, aspirin and hydroxyurea, the patient suffered a dural sinus venous thrombosis, prompting a change in therapy to Ruxolitinib.

Conclusions:

This is the first description of the successful use of ruxolitnib to treat a pediatric patient with PV caused by a JAK2 exon 12 mutation.
Examining the Psychometric Properties of the Taiwanese Version of the Hospice Quality of Life Index
Authors: Longcoy Li-Ting H. , Tai Chun-Yi , Dai Hung-Da , McMillan Susan C. , Doorenbos Ardith Z.
Published: September 2022

Quality of life is an important outcome for people with cancer throughout their cancer trajectory. Having a valid and reliable instrument to measure the quality of life is critical. This cross-sectional study examined the psychometric properties of the Taiwanese version of the Hospice Quality of Life Index among patients with advanced cancer in Taiwan. There were 3 phases: (1) translation of the Hospice Quality of Life Index from English to Mandarin, (2) pilot testing among 30 targeted participants, and (3) field testing to examine validity and reliability. The results of confirmatory factor analysis indicated that the original factor structure of the Hospice Quality of Life Index did not fit the data. After 5 items were deleted from the original questionnaire, principal factor extraction with oblique rotation for exploratory factor analysis yielded 3 subscales: Social/Spiritual Well-Being, Psychological Well-Being, and Functional/Physiological Well-Being. For convergent validity, the small to moderate strength of associations showed shared variance with the Memorial Symptom Assessment Scale. The internal consistency was supported by Cronbach α ranging from 0.77 to 0.86. This study shows early evidence that the quality of life of people with advanced cancer can be appropriately assessed by the Taiwanese Hospice Quality of Life Index.
STING Agonists in Head and Neck Squamous Cell Carcinoma
Authors: Wallington David G. , Contessa Joseph N. , Hayman Thomas J.
Published: September 2022

Despite the development of new treatment paradigms and improved biologic understanding of head and neck squamous cell carcinoma (HNSCC), therapeutic resistance remains a substantial problem, and novel treatment approaches are needed. Stimulator of interferon genes (STING) is a critical regulator of the antitumor response through regulation of both immune-dependent and tumor-intrinsic mechanisms. As such, the STING pathway has emerged as a rational pharmacologic target leading to the development of multiple STING agonists. These compounds have impressive preclinical efficacy as single agents and with PD-1 (programmed death-1) axis agents. However, clinical evaluation in this context has yet to show substantial efficacy. In contrast to monotherapy approaches, activation of STING in combination with DNA-damaging agents has been shown to enhance the effect of these agents in preclinical models and represents a promising approach to improve outcomes in patients with HNSCC. In this review, we will discuss the preclinical and clinical data supporting the use of STING agonists and highlight potential avenues of exploration to unlock the potential of these agents in HNSCC.
Human Papillomavirus–Directed Therapeutics for Human Papillomavirus–Associated Oropharyngeal Cancer
Authors: Campbell Jean S. , Pai Sara I.
Published: September 2022

Despite the availability of prophylactic human papillomavirus (HPV) vaccines, there is a growing incidence of HPV-associated head and neck squamous cell carcinomas (HPV-HNSCC) worldwide. The viral etiology of HPV-HNSCC provides an opportunity to develop personalized immune-based therapies, which target the unique viral- or tumor-specific proteins. Novel HPV-targeted immunotherapeutic approaches in clinical development are reviewed. Early results from these trials highlight new opportunities and potential challenges ahead. Immunotherapies for HPV-associated HNSCCs will require a tailored combinatorial approach based on preexisting mechanisms of host immune resistance. As the field continues to identify the relevant HPV types 16 and 18 immunogenic epitopes that are presented by diverse HLA class I alleles, improved HPV-targeted biologics and clinical monitoring tools can be developed and applied to a broader cancer patient population.
Migraine Headaches in Patients with Upper Extremity Compressive Neuropathy
Authors: Gfrerer Lisa , Lans Jonathan , Chartier Christian , Wenzinger Eric , Austen William G. , Eberlin Kyle R.
Published: September 2022

Background:

Upper extremity nerve compression syndromes and migraines caused by nerve entrapment have many similarities including patient presentation, anatomic findings, and treatment by surgical decompression of affected nerves. Parallels between the two conditions point towards the possibility of shared predisposition. The aim of this study was to evaluate the relationship between migraine and upper extremity nerve compression.

Methods:

9,558 patients that underwent nerve decompression surgery of the upper extremity (median, ulnar, radial and thoracic outlet) as identified by Current Procedural Terminology and International Classification of Diseases (ICD) codes were included in the analysis. ICD codes for migraine and comorbidities included as part of the Elixhauser comorbiditiy index were identified. Bivariate and multivariable logistic regression was performed.

Results:

Median nerve decompression (OR: 1.3, 95% CI: 1.0-1.8, p=0.046) and multiple nerve decompressions (OR: 1.7, 95% CI: 1.2-2.5, p=0.008) were independently associated with higher rates of migraine compared to ulnar nerve decompression and thoracic outlet syndrome. Older age and male gender had a negative association with migraine. History of psychiatric disease, rheumatoid arthritis/collagen vascular diseases, hypothyroidism, hypertension, and chronic pulmonary disease were independently associated with migraine headache.

Conclusion:

Patients who undergo median and multiple nerve decompression are more likely to suffer from migraine headache. It is important to recognize this overlap and provide comprehensive patient screening for both conditions. This shared predisposition and better understanding of a common disease mechanism and genetics, may provide greater insight into the pathogenesis, and therefore treatment of these clinical problems.
Utilization of a Guideline-recommended Imaging Paradigm for Pregnant Patients With Suspicion of Pulmonary Embolism
Authors: McCandlish John A. , Naidich Jason J. , Feizullayeva Chinara , Makhnevich Alexander , Barish Matthew A. , Sanelli Pina C. , Cohen Stuart L.
Published: September 2022

Purpose:

A dose reduction imaging paradigm utilizing chest x-ray (CXR) to triage between computed tomography pulmonary angiography (CTPA) and lung scintigraphy (LS) was introduced in 2001 and adopted in 2012 by the American Thoracic Society/Society of Thoracic Radiology (ATS) guideline for the evaluation of pulmonary embolism in pregnancy. We aimed to assess the utilization of this imaging paradigm preadoption and postadoption by the ATS guideline, and identify factors associated with its utilization.

Materials and Methods:

This retrospective cohort study evaluated consecutive pregnant patients who received CTPA or LS for the evaluation of pulmonary embolism in pregnancy at 2 tertiary hospitals between September 2008 and March 2017, excluding 2012 for guideline release washout. Utilization of the imaging paradigm was defined per patient by the use of CXR before advanced imaging, with CTPA performed following positive CXR and LS performed following negative CXR. Multivariate analyses were performed to assess factors associated with utilization of the imaging paradigm. P<0.05 is considered significant.

Results:

Overall, 9.8% (63/643) of studies utilized the dose reduction imaging paradigm, 13.3% (34/256) before the guidelines, and 7.5% (29/387) after. Multivariable analysis showed that the dose reduction imaging paradigm utilization was higher for inpatients (odds ratio [OR]: 4.5) and outpatients (OR: 3.1) relative to the emergency department patients, and lower for second (OR: 0.3) and third (OR: 0.2) trimester patients, without significant differences by study priority, patient age, or patient race.

Conclusions:

Guideline-recommended dose reduction imaging paradigm utilization was low, and decreased after guideline publication. Utilization varied by patient setting and trimester, which are potential targets for interventions to improve guideline compliance.
Multiple Schwannomas Arising in the Midline Space Between the Bilateral Genioglossus Muscles and Left Submandibular Space
Authors: Iwai Toshinori , Minamiyama Shuhei , Mitsudo Kenji
Published: September 2022

Schwannomas mostly occur as solitary tumors, and multiple schwannomas are very rare. Schwannomas in the submandibular space are extremely rare. Furthermore, schwannomas in the midline space between the bilateral genioglossus muscles are even rarer. We report multiple schwannomas arising in the midline space between the bilateral genioglossus muscles and left submandibular space. Because the common differential diagnosis of the midline deep sublingual lesions does not include schwannoma for the rarity, surgeons should consider schwannoma in the differential diagnosis.
Luminal Preservation Protects the Small Intestine in a Brain-dead Rat Model
Authors: Trentadue Guido , Vecchio Leandro , Kats-Ugurlu Gursah , Vernengo Julieta , Haveman Jan Willem , Ivanoff Ivana , Faber Klaas Nico , Rumbo Martín , Dijkstra Gerard
Published: September 2022

Background.

Intestinal transplantation depends on donation after brain death (DBD). Luminal preservation (LP) has been beneficial against preservation injury in previous studies in animal models, but none include DBD. This study aims to investigate whether these benefits occur also with DBD.

Methods.

Wistar rats (male, N = 9) underwent brain death for 2 h. Thereafter, vascular perfusion was done with University of Wisconsin solution (UW). The small intestine was then explanted and randomized into 3 groups: control (empty segment), LP+PEG (with polyethylene glycol 3350 solution), or LP+UW (with UW), treated and tied shut. Ice-cold UW was used for cold storage. Samples were taken at procurement and after 4 (t = 4) and 8 h (t = 8) of preservation. Histopathological scorings were performed for intestinal preservation injury, subepithelial space, absence of epithelial lining, and hemeoxygenase-1 expression.

Results.

There was low-level mucosal injury (median intestinal preservation injury score 2) at procurement. At t = 4, bowels treated without LP had more damage than LP-treated samples (control score 4, LP+PEG 2 and LP+UW 2, P < 0.001 control versus LP+UW). At t = 8, no benefit of LP was observed (control 2, LP+PEG 3, LP+UW 2). Subepithelial space increased with time and the presence of LP; epithelial lining was better conserved in LP-treated samples. Hemeoxygenase-1 staining showed increased intensity with increased damage, irrespective of treatment.

Conclusions.

Luminal perfusion of the small intestine with UW or PEG protects the mucosa in brain-dead rats for up to 4 h. Fewer benefits of LP were found than previously described in non-DBD models. To mimic the clinical situation, DBD should be included in future animal studies on intestinal preservation.
Cilostazol Administration for Subarachnoid Hemorrhage: A Meta-analysis of Randomized Controlled Trials
Authors: Chen Hongshen , Luo Wenqing , Cai Xianfu , Cai Jing
Published: September 2022

Introduction

The efficacy of cilostazol administration to treat subarachnoid hemorrhage remains controversial. We conduct a systematic review and meta-analysis to explore the influence of cilostazol administration on treatment efficacy for subarachnoid hemorrhage.

Methods

We have searched PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases through July 2020 for randomized controlled trials assessing the effect of cilostazol administration in patients with subarachnoid hemorrhage. This meta-analysis is performed using the random-effect model.

Results

Four randomized controlled trials involving 405 patients were included in the meta-analysis. Overall, compared with control group for subarachnoid hemorrhage, cilostazol intervention can significantly reduce symptomatic vasospasm (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.21–0.60; P = 0.0001) and cerebral infarction (OR, 0.40; 95% CI, 0.22–0.73; P = 0.003) and improve no or mild angiographic vasospasm (OR, 2.01; 95% CI, 1.19–3.42; P = 0.01) and an mRS score of 2 or less (OR, 2.70; 95% CI, 1.09–6.71; P = 0.03), but revealed no obvious influence on severe angiographic vasospasm (OR, 0.53; 95% CI, 0.27–1.02; P = 0.06). There were no increase in adverse events (OR, 1.17; 95% CI, 0.54–2.52; P = 0.69), hemorrhagic events (OR, 0.62; 95% CI, 0.06–6.27; P = 0.69), and cardiac events (OR, 2.14; 95% CI, 0.44–10.27; P = 0.34) after the cilostazol intervention than control intervention.

Conclusions

Cilostazol treatment may be effective to treat subarachnoid hemorrhage in the terms of symptomatic vasospasm, cerebral infarction, no or mild angiographic vasospasm, and an mRS score of 2 or less.
Pneumonia in Sudan; Systematic Scoping Review of Literature and Meta Analysis
Authors: Mohamed D M , SalahEldin M A , Idris A B , Idris E B , Mohamed S G , Badawi M M
Published: September 2022

In addition to excessive burden of non-communicable diseases, natural and manmade disasters and internal conflicts, Sudan is predominantly susceptible to communicable diseases such as Malaria, Tuberculosis, and Pneumonia, which bring about a burden of infectious diseases and demand for high quality health care. According to the WHO as well as the Sudan Health Observatory, Pneumonia is one of the leading causes of death in Sudan. This study therefore aimed to determine pneumonia infection prevalence among Sudanese as well as its related risk factors. A systematic review of the literature was conducted in the 1stof December 2020. The review was regulated in accordance with PRISMA. After abstract and full text screening only seventeen articles met our inclusion criteria and passed the quality assessment procedure. Seven included studies determined prevalence of pneumonia; the overall pooled prevalence was around 30%. Furthermore, twelve research articles investigated risk factors related to pneumonia among Sudanese population. Further research with larger sample sizes targeting risk factors of pneumonia among Sudanese population is needed to be conducted.
Impact of COVID-19 on lifestyle and mental wellbeing in a drought-affected rural Australian population: A mixed method approach
Authors: Carlson Jack , Chan Kevin , Gray Jonah , Xue Houston , Reed Krista , Bailey Jannine K , Dutton Tegan , Osuagwu Uchechukwu Levi , Vines Robyn
Published: September 2022

Background

The Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented social and economic disruption, accompanied by the enactment of a multitude of public health measures to restrain disease transmission. These public health and social measures have had a considerable impact on lifestyle and mental wellbeing, which has been well-studied in metropolitan populations, but very little in rural populations. Additionally, the development and use of a standardised scoring system for an overall assessment of patient lifestyle management, and monitoring of changes in these, may be warranted in clinical practice.

Methods

The associations between psychological distress and changes in SNAPS health behaviours (smoking, nutrition, alcohol, physical activity, sleep) since the onset of COVID-19 in rural Australia were examined. A cross-sectional anonymous online survey was distributed among adults in the Western New South Wales Primary Health Network in August 2020. The survey included measures of psychological distress, income, disposition, lifestyle factors and behaviours during the pandemic, as well as changes in lifestyle due to COVID-19. A novel Global Lifestyle Score (GLS) was generated as a holistic assessment of lifestyle across multiple domains.

Results

The survey was completed by 308 individuals (modal age group: 45-54 years old, 86.4% female). High distress on the K5 scale was present in over one-third of respondents (n=98, 34.3%). Negative change was reported for sleep (24.4%), nutrition (14.3%), alcohol (17.8%), physical exercise (33.8%) and smoking (26.6%) since the onset of the pandemic. Additionally, changes in sleep, nutrition, physical activity and smoking were associated with distress. Respondents with a poor lifestyle (GLS) during the pandemic were significantly more distressed. Perceived COVID-19 impact was associated with high distress, level of drought impact and loss of income.

Conclusion

High rates of distress amongst rural Australians during the COVID-19 pandemic was linked, worsening lifestyles as measured by the GLS and loss of income. Lifestyle promotion strategies should be considered by health professionals for the management of crisis-related distress. Further research may explore the impact of COVID-19 on a larger population, including a greater proportion of male respondents, and the impact of modifying lifestyle factors on the reduction of distress in the context of a stressor such as this pandemic.
Synapsin autoantibodies during pregnancy are associated with fetal abnormalities
Authors: Bünger Isabel , Kreye Jakob , Makridis Konstantin , Höltje Markus , Rasmussen Helle Foverskov , van Hoof Scott , Ullrich Tim , Sedlin Eva , Hoffmann Christian , Milovanovic Dragomir , Paul Friedemann , Meckies Jessica , Verlohren Stefan , Henrich Wolfgang , Chaoui Rabih , Kaindl Angela , Prüss Harald
Published: September 2022

Anti-neuronal autoantibodies can be transplacentally transferred during pregnancy and may cause detrimental effects on fetal development. It is unclear whether autoantibodies against synapsin-I, one of the most abundant synaptic proteins, are associated with developmental abnormalities in humans. We prospectively recruited a cohort of 263 pregnant women and detected serum synapsin-I IgG autoantibodies in 13.3%. Seropositivity was strongly associated with abnormalities of fetal development including intrauterine growth retardation. This finding indicates that these autoantibodies may be clinically useful developmental biomarkers and/or even directly participate in the disease process, thus being amenable to antibody-targeting interventional strategies in the future.
Development of Q-LAAD, an allonamer-based antigen test for the rapid detection of SARS-CoV-2
Authors: Overgaard Elise , Li Shiwei , Covert Hunter J. , Tawara Ken , Poe Aidan M. , Shults N. Hagan , Chernish Aliona A. , Sweet Brandi , Gonzales Cara R. , Gibard Clémentine F.N. , Burden Steven J.
Published: September 2022

The SARS-CoV-2 virus has spread globally causing coronavirus disease 2019 (COVID-19). Rapidly and accurately identifying viral infections is an ongoing necessity. We used the systematic evolution of ligands by exponential enrichment (SELEX) technique to produce a DNA allonamer with two distinct binding domains made allosteric through a linker section; one domain binds SARS-CoV-2 spike (S) protein, inducing a conformational change that allows the reporter domain to bind a fluorescent reporter molecule. We used bead-based fluorescence and immunofluorescence assays to confirm the allonamer’s affinity and specificity for S-protein and confirmed that the allonamer can bind to S-proteins with mutations corresponding to those of the alpha, beta, gamma, and delta variants. We then developed the allonamer-based Quantum-Logic Aptamer Analyte Detection (Q-LAAD) test, a rapid, high-throughput antigen test for qualitative detection of SARS-CoV-2 in clinical settings. We validated Q-LAAD against retrospective and prospective clinical anterior nasal swab samples collected from symptomatic patients suspected of having COVID-19. Q-LAAD showed 97% sensitivity and 100% specificity compared to the RT-qPCR assay. Q-LAAD has a limit of detection (LOD) of 1.88 TCID50/mL, is cost-effective and convenient, and requires only a common fluorescence plate reader. Q-LAAD may be a useful clinical diagnostic tool in the fight against SARS-CoV-2.

HIGHLIGHTS

Allonamers are allosterically-regulated DNA aptamers with multiple binding pockets

Q-LAAD uses allonamers to detect SARS-CoV-2 spike protein in clinical samples

Q-LAAD has high sensitivity and specificity and a low limit of detection

Q-LAAD can detect spike proteins from multiple SARS-CoV-2 variants

Q-LAAD is a dynamic, cost-effective rapid antigen test for detection of SARS-CoV-2
Preponderant Myosin Super-Relaxed State In Skeletal Muscle From Endurance Athletes
Authors: Lewis Christopher T. A. , Tabrizian Lee , Nielsen Joachim , Laitila Jenni , Beck Thomas N. , Aagaard Per , Hokken Rune , Laugesen Simon , Ingersen Arthur , Andersen Jesper L. , Soendenbroe Casper , Helge Jørn W. , Dela Flemming , Larsen Steen , Sahl Ronni E. , Rømer Tue , Hansen Mikkel T. , Frandsen Jacob , Suetta Charlotte , Ochala Julien
Published: September 2022

It has recently been established that myosin, the molecular motor protein, is able to exist in two conformations in relaxed skeletal muscle. These conformations are known as super-relaxed (SRX) and disordered-relaxed (DRX) states and are finely balanced to optimize skeletal muscle metabo-lism. Indeed, SRX myosins are thought to have a 10-fold reduction in ATP turnover compared to DRX myosins. Here, we investigated whether chronic physical activity in humans would be associated with changes in the proportions of SRX and DRX skeletal myosins. For that, we isolated mus-cle fibres from various athletic and sedentary populations and ran a loaded Mant-ATP chase proto-col. We observed that, in endurance-trained athletes, the amounts of myosin molecules in the SRX state was significantly greater than in age-matched sedentary individuals or than in strength athletes. To further assess whether this change would have an impact on the potency of a SRX-inducing pharmacological compound, Mavacamten, we performed similar analyses as above with and without the drug in muscle fibres from endurance athletes. Surprisingly, we found that 0.3 μM of Mava-camten had only marginal effects. Altogether, our results indicate that chronic endurance training-status influences resting skeletal myosin conformations, and Mavacamten potency. Our findings also emphasize that environmental stimuli such as exercise can re-wire the molecular metabolism of human skeletal muscle through myosin.

Lewiset al., investigate how training-status influences myosin conformations involved in the resting metabolism of skeletal muscle. They find that, in endurance-trained athletes, skeletal myosin preferentially adopts an energy-saving conformation known as super-relaxed state, lowering the metabolic rate and affecting the potency of a super-relaxed state-inducing drug, Mavacamten.
Marginal Zone B Cells are Necessary for the Formation of Anti-Donor IgG After Allogeneic Sensitization
Authors: Kallarakal Melissa A. , Cohen Gregory , Ibukun Francis I. , Krummey Scott M.
Published: September 2022

The formation of anti-MHC antibody is a significant barrier to improved outcomes in organ transplantation. Patients with pre-formed anti-HLA antibodies have limited options for suitable donors, and the formation of donor-specific anti-HLA antibodies after transplantation is a harbinger of graft rejection. Despite the recognized importance of anti-HLA antibodies, the mechanisms responsible for the differentiation of B cells after exposure to allogeneic antigen are poorly understood. In order to evaluate the differentiation of B cells in response to allogeneic antigen, we used a model of H-2bC57/Bl6 sensitization with H-2dantigen. We found that although the formation of anti-H-2dIgG was robust, few class switched B cells and germinal center B cells were formed. Sensitization induced weak expression of classical memory B cell markers, but we observed populations of CD21+and IRF4+B cells, that corresponded to an increase in the frequency of marginal zone phenotype B cells after sensitization. Depletion of marginal zone B cells prior to sensitization resulted in a significant dimunition of anti-H-2dIgG and also fewer germinal center B cells. These results demonstrate a previously unappreciated role for marginal zone B cells as a reservoir of alloreactive B cells that are activated by allogeneic antigen.
Leveraging vision to understand curiosity
Authors: Cohanpour Michael , Aly Mariam , Gottlieb Jacqueline
Published: September 2022

Humans are immensely curious and motivated to reduce uncertainty. Inspired by studies of sensory uncertainty, we hypothesized that visual areas provide multivariate representations of uncertainty, which are read out by higher-order areas that encode confidence and, ultimately, translated into curiosity. During fMRI, participants rated their confidence in identifying distorted images of animals and objects and their curiosity to see the clear image. We found that curiosity peaked at low confidence. To link sensory certainty and curiosity, we estimated “OTC Certainty” as the product of absolute and relative evidence for animals vs. object categories in occipitotemporal cortex (OTC) while participants viewed the distorted image. OTC Certainty negatively correlated with curiosity, while univariate activity in two frontal regions – vmPFC and ACC – positively correlated with confidence. The relationship between OTC certainty and curiosity was mediated by the vmPFC but not ACC. The results reveal neural mechanisms that generate curiosity from representations of uncertainty.