bluuebunny/crossref_metadata_2025 huggingface dataset:
10249-PEDT-8 CURRENT STATUS AND ISSUES OF PEDIATRIC DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
Authors: Suzuki Tomonari , mizuno reina , shirahata mitsuaki , adachi junihci , nishikawa ryo , fujimaki takamitsu , mishima kazuhiko
Published: December 2023

that predominantly occurs in childhood, with a median survival of less than one year. Herein we present a recent case of DIPG and discuss the current status and future challenges. The patient was a 7-year-old boy who complained of tinnitus, headaches, and unstable gait. The MRI showed diffuse enlargement of the pons, and the contrast-enhanced T1-weighted image exhibited an irregular ring-like enhancement. Neurologically, he presented with left abducens nerve palsy, horizontal gaze nystagmus, significant left ataxia, and truncal ataxia. As the lesion extended to the left cerebellar peduncle, a stereotactic biopsy was performed. However, postoperative bleeding occurred, resulting in transient consciousness disturbance, left facial palsy, speech disturbance, and dysphagia, necessitating enteral nutrition management. The pathological diagnosis was high-grade glioma, IDH wild type, H3K27M mutation (-), TERTp wild type, BRAF V600E mutation (-), BRAF fusion (-), and MGMT unmethylated. After surgery, the patient received radiation therapy (54Gy/30fr), and his symptoms improved, allowing him to resume oral intake. Post-irradiation, the lesion shrank, and he was discharged home without assistance. However, six months later, his symptoms worsened, and he started taking temozolomide orally, but the effect was limited. Nine months later, he became unable to take oral medication, and a central venous port was placed. We coordinated with home care physicians to provide intravenous and palliative treatments, but respiratory and consciousness disturbances gradually worsened, and he died 10 months after the initial diagnosis. The median survival of DIPG patients treated at our hospital is currently 10.5 months, and this case followed a typical course. The development of novel treatments is desired, but due to the rarity of the disease, conducting comparative trials is challenging. Hence, registry data forming a control group are necessary. Additionally, transitioning to home-based palliative care and sharing information on supportive therapies are also critical tasks.
10255-BOT-5 EXOSOMAL MIRNAS RELEASED FROM GLIOBLASTOMA CELLS AFTER BNCT TARGET CELL PROLIFERATION AND SURVIVAL SIGNALS
Authors: Natsuko Kondo , Kinouchi Tadatoshi , Sakurai Yoshinori , Suzuki Minoru , Hirata Eishu , Okada Masayasu , Natsumeda Manabu
Published: December 2023

Boron neutron capture therapy (BNCT) is a tumor -selective particle radiation therapy. In BNCT, p-boronophenyl alanine, which is actively taken up by tumor cells through LAT1 transporter, a member of the system L family of heterodimeric, sodium-independent, amino acid transporters, is administrated to patients, and thermal or epithermal neutron is irradiated to tumor tissue of the patients. Nuclear capture and fission reactions between boron-10 and thermal neutron occurred only in tumor cells produce high- linear energy transfer (LET) alpha particles and recoiling lithium-7 (7Li). These high LET particles have very short pathlength (5-9 μmeter), and kill boron-10 containing tumor cells sparing adjacent normal tissue cells. BNCT was applied to malignant glioma, the most devastating tumor and has prolonged the survival of malignant glioma patients. In this study, we comprehensively investigated the micro RNAs (miRNAs) in exosomes derived from BNCT-treated glioblastoma U87 MG cells using microarray. Comparing with non-treated cells, more than 300 up-regulated miRNAs or 100 down-regulated miRNAs were detected in BNCT-treated cells. From the results of the prediction analysis of the target genes which interact with the miRNAs, the pathway analysis was performed. We found significantly associated pathways, such as Focal adhesion-PI3K-Akt-mTOR, Ras, MAPK, etc. miRNAs in exosomes released from BNCT-treated glioblastoma cells may suppress such essential pathways for cell proliferation and survival.
10259-NQPC-9 CONTROVERSY ON INVASIVE AIRWAY MANAGEMENT IN PATIENTS WITH BRAIN STEM MALIGNANT GLIOMA.
Authors: Ikeda Kensuke , Saito Kuniaki , Yamagishi Yuki , Sasaki Nobuyoshi , Kobayashi Keiichi , Nakatomi Hirofumi , Nagane Motoo
Published: December 2023

INTRODUCTION

The prognosis for patients with malignant gliomas of the brainstem is poor. As the tumor progresses into the medulla oblongata, the lower cranial nerves are affected, resulting in dysphagia and eventually respiratory paralysis. On the other hand, higher cerebral function is often preserved, making it a palliative medical issue whether to perform invasive procedures to secure the airway. We report here three characteristic cases treated at our hospital.

CASE 1

A-60-year-old male patient with diffuse midline glioma of the medulla oblongata was admitted to our hospital for radiation therapy and concomitant temozolomide. His consciousness level was clear, but dysphagia was noted. Although he was at risk for aspiration and choking, he did not wish to undergo surgery to prevent aspiration. After treatment was started, he died of choking.

CASE 2

A-50-year-old male patient with recurrent astrocytoma in the brainstem was admitted for bevacizumab monotherapy. Despite the treatment, his dysphagia gradually worsened, and he developed respiratory failure due to aspiration pneumonia, resulting in tracheal intubation. Subsequently, he underwent glottis closure, and as a result, he lost his speech but recurrence of aspiration pneumonia and choking were prevented.

CASE 3

A-50-year-old male patient with cerebellar glioma invading brainstem was admitted due to aspiration pneumonia. He was disoriented and required heavy care. He did not wish to undergo surgery to prevent aspiration, but with antimicrobial therapy and frequent oral suctioning, his aspiration pneumonia was cured.

DISCUSSION

Although invasive procedures are generally avoided in terminal-stage cancer patients, anti-aspiration procedures such as tracheostomy and glottis closure may be considered for the conscious patients with malignant glioma in the brainstem. These procedures might be an option at the end of life to avoid painful death due to choking and to prevent deterioration of the patient's condition due to repeated aspiration pneumonia.
10264-NQPC-10 ACTIVITY RECORD OF THE JAPAN BRAIN TUMOR ALLIANCE, AND THE NEEDS OF BRAIN TUMOR PATIENTS AND FAMILIES
Authors: Nomura Keiko , Tagawa Hisato , Yamaguchi Shuji , Gatellier Laureline
Published: December 2023

Brain tumor is a major shock at diagnosis for patients and their families, and is likely to have physical, emotional, financial, and social impacts to them. These impacts are not limited to during treatment, but affect their lives even after the treatment is over. Therefore, continuous support is a must for brain tumor patients and their families. The Japan Brain Tumor Alliance (JBTA) was established in 2006 and provides nationwide patient support. Our main activities are 1) support for patients and their families, 2) provision of the latest information and networking, 3) contribution to advocacy and science, and 4) awareness-raising activities. In (1), we hold monthly social gatherings where patients and their families can share their daily problems and challenges. In (2), JBTA actively collaborated with other patient groups in Japan and abroad, and in (4), continues to provide up-to-date information via website and social media. JBTA has been particularly active in 3) by holding the seminars by health care professionals and the meetings with neurosurgeons in Japan Clinical Oncology Group to discuss newly planned clinical trials. Our cooperation with rehabilitation therapists and nurses resulted in a brochure for patients, "Brain Tumor Support Book". As members of the committee of supportive care for brain tumor patients which was established in the Japan Society of Neuro-Oncology, collaboration with various health care professionals was made to prepare leaflets for supportive care including advance care planning. Since April 2023, a survey to find out the needs of patients and caregivers is on-going. The interim report as of June 2023 showed that patients and their caregivers have difficulties to share their concerns and problems, and that they have few opportunities to receive support from multidisciplinary professionals. Therefore, more supports for brain tumor patients and their families are needed in their daily lives.
Network targeting combination therapy of synthetic lethal vulnerabilities in 9p21-deficient glioblastoma: A case report
Authors: Castro Michael P , Dittmar Kristin
Published: December 2023

Background

Patients with relapsed or progressive glioblastoma only rarely respond to salvage therapies. Nevertheless, comprehensive genomic profiling can provide insight that can identify promising approaches. Signaling pathway analyses have revealed synthetic lethal partnerships, which create the possibility of targeting vulnerabilities arising from the loss of tumor suppressor genes. For synthetic lethal vulnerabilities that are not present in normal tissues, lethal cytotoxicity against cancer cells can be achieved without the necessity of causing normal tissue toxicity. This case report describes a patient with progressive glioblastoma with homozygous deletion of chromosome 9p21.

Methods and Results

Vulnerabilities created by CDKN2A and MTAP loss were exploited with pemetrexed, bevacizumab, and candesartan to achieve a clinically meaningful remission by targeting multiple synthetic lethal nodes.

Conclusion

Synthetic lethality can reveal the basis for exceptional responsiveness, thus extending the utility of molecular profiling and fulfilling the promise of precision medicine.
Lived experience of work and long COVID in healthcare staff
Authors: Torrance N , MacIver E , Adams N N , Skåtun D , Scott N , Kennedy C , Douglas F , Hernandez-Santiago V , Grant A
Published: December 2023

Background

Healthcare workers (HCWs) had a greater occupational risk of exposure to coronavirus disease 2019 (COVID-19) and reported higher rates of long COVID (LC). This has implications for the provision of health care in already stretched health services.

Aims

This study explored the impact of LC on a range of UK National Health Service (NHS) HCWs, their health and well-being, the effect on work patterns, and occupational support received.

METHODS

Mixed-methods study, online survey and qualitative interviews. Participants self-reporting LC symptoms were recruited through social media and NHS channels. Interviews used maximum variation sampling of 50 HCWs including healthcare professionals, ancillary and administration staff. Thematic analysis was conducted using NVivo software.

RESULTS

A total of 471 HCWs completed the online survey. Multiple LC symptoms were reported, revealing activity limitations for 90%. Two-thirds had taken sick leave, 18% were off-work and 33% reported changes in work duties. There were few differences in work practices by occupational group. Most participants were working but managing complex and dynamic symptoms, with periods of improvement and exacerbation. They engaged in a range of strategies: rest, pacing, planning and prioritizing, with work prioritized over other aspects of life. Symptom improvements were often linked to occupational medicine, managerial, colleague support and flexible workplace adjustments.

Conclusions

LC has a significant impact on the lives of HCWs suffering prolonged symptoms. Due to the variability and dynamic nature of symptoms, workplace support and flexible policies are needed to help retain staff.
Occupational effects in patients with post-COVID-19 syndrome
Authors: Green C E , Leeds J S , Leeds C M
Published: December 2023

Background

It is well recognized that some individuals experience persistent symptoms following an initial SARS-CoV-2 infection. Symptoms affect physical, cognitive and mental well-being and can adversely impact activities of daily living, including the ability to work.

Aims

To examine the impact of post-COVID-19 syndrome with respect to effects on quality of life and impact on work in a cohort of people referred to a ‘Long COVID’ service.

METHODS

All triaged patients (over 18 years with symptoms more than 12 weeks since the initial infection) completed a symptom assessment questionnaire. Occupation and working status (at work, at work struggling with symptoms and off work) were also recorded. Impact on function and quality of life was assessed using the EQ5D5L questionnaire.

RESULTS

A total of 214 patients (median age 51.0 years, 135 females) were seen from January to September 2021. Analysis of occupational status showed: 18% were working, 40% were working but struggling and 35% had stopped working due to symptoms. Those unable to work reported significantly more fatigue, a greater perception of the need for support and lower quality-of-life scores.

Conclusions

This study shows the extensive impact of post-COVID-19 syndrome on the ability to return to work. Specific return-to-work guidance is needed to support a large proportion of those struggling with the condition. The involvement of the Occupational Health team should form part of the multidisciplinary, collaborative approach to support rehabilitation and improve long-term outcomes for this condition.
The experience of youth on the waitlist for gender-affirming care in Manitoba
Authors: Bhatla Jennifer L , James Kristin , Lamb Kaylen (Kay) A E , Neault-Lount Chrystal , Protudjer Jennifer L P , Reitmeier Shayne D , Cooney Megan , Wicklow Brandy
Published: December 2023

Objectives

Waitlist times for adolescents to be seen for initial assessment for gender-affirming hormone therapy in Manitoba, Canada are often 2 years. The purpose of this study was to understand the experiences of waitlisted youth and to assess the impact of social work contact for accessing relevant resources.

Methods

A qualitative, semi-structured interview study was conducted. Youth aged 14 to 17 years on the provincial transgender clinic waitlist for 12 to 24 months for gender-affirming hormone therapy assessment and their caregivers were recruited. Eight youth and nine caregivers were interviewed. Separate interviews were conducted for youth and their caregivers. All interviews were virtual, recorded, and transcribed prior to thematic analysis.

Results

Three themes and eight subthemes were identified. Youth (n = 8) and caregivers (n = 9) described barriers to supported transition in the following three themes: (1) ‘In a Black Hole’: Describing the lack of communication, relevant resources, and mental health supports, (2) ‘Structural Transphobia’: A summary term outlining the attitudinal, technological, physical, and architectural barriers faced by the participants, and (3) ‘Manitoba: An Information Desert’: describing the systemic barriers faced including lack of knowledgeable providers and reliable information within the province.

Conclusions

Although delays in gender-affirming therapy were noted, youth socially transitioned and accessed existing resources. However, mental health concerns persisted, and participants felt frustrated and unsupported during their extensive wait times. Improved experiences may be achieved by additional communication from the clinic, hands-on assistance with accessing relevant resources, and an improved online presence.
Does higher education matter in policing? An examination of the promotional process to sergeant
Authors: Chavez Enrique , Torres Christopher E , Lee-Silcox Joelle
Published: December 2023

The police sergeant is often regarded as the most influential position in any law enforcement agency, given their direct effect on officer behaviour. As the gateway to police management, the promotion to sergeant offers an opportunity to examine the importance of the growing role of higher education in policing. In analysing the relationship between different levels of higher education and the sergeant promotional examinations, this study found that those with graduate degrees are more likely to become sergeants. While this relationship is striking, the most crucial predictor of the promotion to sergeant belongs to the dominant ethnic group in the agency. Whether in the written exam or interview components of the sergeant’s promotion process, police agencies do not appear to have captured the benefits of higher education in the first rung of the promotion to senior management. Policy implications and avenues for future research are discussed.
Phase diagram near the quantum critical point in Schwinger model at θ = π: analogy with quantum Ising chain
Authors: Ohata Hiroki
Published: December 2023

The Schwinger model, 1D quantum electrodynamics, has CP symmetry at θ = π due to the topological nature of the θ term. At zero temperature, it is known that as the fermion mass increases, the system undergoes a second-order phase transition to the CP broken phase, which belongs to the same universality class as the quantum Ising chain. In this paper, we obtain the phase diagram near the quantum critical point (QCP) in the temperature and fermion mass plane using first-principle Monte Carlo simulations, while avoiding the sign problem by using the lattice formulation of the bosonized Schwinger model. Specifically, we perform a detailed investigation of the correlation function of the electric field near the QCP and find that its asymptotic behavior can be described by the universal scaling function of the quantum Ising chain. This finding indicates the existence of three regions near the QCP, each characterized by a specific asymptotic form of the correlation length, and demonstrates that the CP symmetry is restored at any nonzero temperature, entirely analogous to the quantum Ising chain. The range of the scaling behavior is also examined and found to be particularly wide.
Examining the relationship between autism spectrum disorder in children whose mother had labour epidural analgesia for their birth
Authors: Zamstein Omri , Sheiner Eyal , Binyamin Yair , Pariente Gali , Wainstock Tamar
Published: December 2023

BACKGROUND

Controversy exists regarding the association between autism spectrum disorder (ASD) in children whose mother had labour epidural analgesia for their birth, as the few existing investigations have reported mixed findings.

OBJECTIVE

This study aims to evaluate the possibility of an association in our heterogeneous population.

DESIGN

A retrospective population-based cohort study.

SETTING

Vaginal deliveries that took place between the years 2005 and 2017 at Soroka University Medical Center, a tertiary referral hospital in Israel, and a follow-up on the incidence of ASD in the children.

PATIENTS

A hundred and thirty-nine thousand, nine hundred and eighty-one labouring patients and their offspring.

MAIN OUTCOME MEASURES

The incidence of children diagnosed with ASD (both hospital and community-based diagnoses) was compared based on whether their mothers had received labour epidural analgesia during their labour. A Kaplan–Meier survival curve compared cumulative incidence of ASD. A Cox proportional hazards model was used to control for relevant confounders.

RESULTS

Labour epidural analgesia was administered to 33 315 women. Epidural analgesia was more common among high-risk pregnancy groups (including pregnancies complicated with diabetes mellitus, hypertensive disorders, intrauterine growth restriction, and oligohydramnios; P < 0.001). In a Cox proportional hazards model, the association between epidural analgesia during labour and ASD in the children lost statistical significance following adjustment for confounders such as maternal age, gestational age, hypertensive disorders, diabetes mellitus, and ethnicity [adjusted hazard ratio = 1.13, 95% confidence interval (CI), 0.96 to 1.34, P = 0.152].

CONCLUSION

In our population, after adjusting for confounders, epidural analgesia is not independently associated with autism spectrum disorder in the children. These findings enhance our knowledge regarding the safety of epidural analgesia and enable patients to make informed decisions about their pain relief techniques during labour.
Comparison of visual outcomes of bilateral dual-technology diffractive intraocular lens vs blended enhanced monofocal with dual-technology intraocular lens
Authors: Hida Wilson Takashi , Moscovici Bernardo Kaplan , Cortez Cesar Martins , Colombo-Barboza Guilherme Novoa , Tzelikis Patrick Frensel de Moraes , Motta Antonio Francisco Pimenta , De Medeiros Andre Lins , Nose Walton , Carricondo Pedro Carlos
Published: December 2023

Purpose:

To compare clinical outcomes after implantation of TECNIS Synergy (ZFR00V) intraocular lenses (IOLs) in both eyes and implantation of the TECNIS Synergy and TECNIS Eyhance (ICB00) combination in patients undergoing cataract surgery.

Setting:

Department of Cataract, Hospital Oftalmológico de Brasilia (HOB), Brasília, Brazil.

Design:

Prospective, interventional, randomized, parallel-group study.

Methods:

Patients were categorized into 2 groups: Group 1: ZFR00V IOL was implanted in both eyes. Group 2: An ICB00 IOL was implanted in the dominant eye, and a ZFR00V IOL was implanted in the nondominant eye.

Results:

Visual acuity was similar between the 2 groups (95% CI <0.1 logMAR). A superior visual acuity of ≥ 20/25 (at −2.00 to −2.50 diopters [D]) was achieved in Group 1 (bilateral ZFR00V) than in Group 2 (combination of ZFR00V/ICB00). The binocular defocus curve demonstrated better visual acuity at 40 cm (−2.00 D) and 50 cm (−2.50 D) in Group 1 than in Group 2 (P < .05). Similar contrast sensitivity values were observed between the 2 groups. Patients in Group 1 reported higher satisfaction (completely satisfied) than those in Group 2 (P < .05). However, halos and glare were more pronounced in Group 1 than in Group 2 (P < .05).

Conclusions:

Both presbyopia-correcting IOL combinations showed similar binocular visual acuity results. Group 1 demonstrated enhanced visual acuity in the defocus curve at 40 cm (−2.00 D) and 50 cm (−2.50 D). Comparable contrast sensitivity outcomes were observed in both groups. Patients were more completely satisfied in Group 1 than in Group 2, despite the higher frequency of postoperative nighttime halos and glare.
Surgical outcomes of intraocular lens iris suture fixation in eyes with residual capsule support
Authors: Alsetri Hasan , Masket Samuel , Fram Nicole , Schoen Marisa , Cabang Julieanne , Pagal Jared , Kwong Stephen , Fram Ashlyn , Sandoval Hector
Published: December 2023

Purpose:

To evaluate the safety and refractive outcomes of eyes after intraocular lens (IOL) iris suture fixation (ISF).

Setting:

Private practice, Los Angeles, California.

Design:

Nonrandomized and unmasked retrospective chart review.

Methods:

Eyes that underwent IOL exchange or repositioning with ISF with at least 270 degrees of capsular support were included. Eyes with less than 270 degrees of capsular support and eyes with iris damage were excluded. The primary outcome measures included incidence of cystoid macular edema (CME), IOL dislocation requiring refixation, and chronic inflammation. Secondary outcome measures included worsening intraocular pressure (IOP) control, retinal tear or detachment, worsening of corrected distance visual acuity (CDVA), and corneal decompensation. Refractive outcomes for 26 subgrouped eyes included mean and median spherical equivalent refraction accuracy (SERA), and percentage of eyes within 0.5 diopter (D) and 1 D of the refractive target.

Results:

The study included 53 eyes of 50 patients. CME: 2/53 (3.8%), IOL dislocation requiring refixation: 2/53 (3.8%), chronic inflammation: 1/53 (1.9%), worsening IOP control: 5/53 (9.4%), retinal tear or detachment: 2/53 (3.8%). No patient experienced worsening of CDVA from baseline or corneal decompensation. Mean SERA ± SD −0.35 ± 0.29 D, median SERA −0.37 D. Of the 26 eyes subgrouped for refractive analysis, 73% were within 0.5 D and 100% were within 1 D of the desired refractive outcome.

Conclusions:

ISF can offer stability for sulcus-fixated IOLs provided there is some residual capsule support. Although there are measurable complications, there is a relatively low side effect profile. The refractive error tended to be myopic, indicating the need for further refinement of IOL power predictive formulas.
The Stapes Head Coupler—A Flexible and Safe Option for Vibroplasty
Authors: Spahn Bjoern , Koestler Carolina , Herrmann David , Voelker Johannes , Engert Jonas , Kurz Anja , Hagen Rudolf , Cebulla Mario , Rak Kristen
Published: December 2023

Objective

To investigate the surgical approach and the audiological outcome of a stapes head coupler in active middle ear implant surgery.

Study design

Retrospective data analysis.

Setting

Tertiary referral center with a large active middle ear implant program.

Patients

Twelve patients with active middle ear implant surgery.

Interventions

Therapeutic surgical approach for hearing rehabilitation in human subjects.

Main Outcome Measure(s)

Auditory brainstem response, sound field thresholds, vibrogram, speech perception in the Freiburger monosyllabic word test.

Results

The stapes head was attached safely in different coupling situations. Audiological outcomes were similar to the audiological performance of established vibroplasty couplers presented in the literature.

Conclusion

The stapes head coupler is a new and safe tool for vibroplasty with a good audiological outcome.
Comparison of Transcutaneous and Percutaneous Implantable Hearing Devices for the Management of Congenital Aural Atresia: A Systematic Review and Meta-Analysis
Authors: Gutierrez Jorge A. , Shannon Christian M. , Nguyen Shaun A. , Meyer Ted A. , Lambert Paul R.
Published: December 2023

Objective

To compare audiometric outcomes, complications, and revisions required for percutaneous (pBCD) versus transcutaneous (tBCD) implantable bone-conduction devices for the treatment of hearing loss associated with congenital aural atresia (CAA).

Databases Reviewed.

PubMed, Scopus, CINAHL.

Methods

A systematic review was performed searching for English language articles from inception to December 14, 2022. Studies reporting audiometric outcomes or complications for either pBCDs or tBCDs for the treatment of CAA were selected for inclusion. A meta-analysis of single means and meta-analysis of proportions with comparison (Δ) of weighted proportions was conducted.

Results

A total of 56 articles with 756 patients were selected for inclusion. One hundred ninety patients were implanted with pBCDs, whereas the remaining 566 were implanted with tBCDs. Mean pure-tone audiometry improvement in the pBCD group (39.1 ± 1.1 dB) was significantly higher than in the tBCD group (34.6 ± 1.6 dB; Δ4.5 dB; 95% confidence interval, 4.2–4.7 dB; p < 0.0001). The average improvement in speech reception threshold was 38.6 ± 2.5 dB in the percutaneous group as compared with 32.7 ± 1.6 dB in the transcutaneous group (Δ5.9 dB [5.3–6.5 dB], p < 0.0001). Overall complication rates for patients implanted with pBCDs and tBCDs were 29.0% (15.7–44.4%) and 9.4% (6.5%–13.0%), respectively (Δ19.6% [12.0–27.7%], p < 0.0001).

Conclusions

Patients with CAA implanted with pBCDs had significantly better audiometric outcomes than those implanted with tBCDs. However, complication rates were significantly higher among the pBCD group.
A New Way of Learning
Authors: Roznik Maria
Published: December 2023

The growing use of quick response (QR) codes has become a way to engage learners and promote critical thinking. QR codes are incorporated into a table top activity with codes placed onto a body map to guide users through a patient scenario. The codes are scanned to identify patient problems and anticipate care and a debrief session following the activity. This technology offers unlimited learning experiences and can be used in any disciplines of nursing.
An Interruption Management Education Bundle
Authors: Schroers Ginger , Pfieffer Jill , Andersen Bridget , O'Rourke Jenny
Published: December 2023

Background:

Interruptions and distractions are pervasive in health care settings, increase risks for errors, and decrease task efficiency. Researchers recommend the use of strategies to mitigate their negative effects.

Purpose:

The purpose was to assess the feasibility and acceptability of (1) an education bundle that included an interruption management strategy and (2) simulated scenarios with embedded interruptions and distractions.

Methods:

Nineteen undergraduate nursing students participated in this repeated-measures, multimethods feasibility study. Data on interruption management behaviors were collected across 3 timepoints via direct observation of individual-simulated medication administration. Participants’ perceptions of the education bundle were explored via semistructured interviews.

Results:

Participants described the simulated scenarios as realistic and interruption management strategy as easy to use and remember. Participants voiced increased confidence in handling interruptions after learning the strategy. The strategy averaged 4 seconds to apply.

Conclusions:

Findings support the feasibility and acceptability of the bundle and need for studies to investigate the impact of the strategy on errors and task durations.
Student Perception of Diversity, Equity, and Inclusion Curricular Threads on Nursing Practice
Authors: Dowling Tomeka , Toll Crystal , Whitlow Malinda , Hicks Frank D.
Published: December 2023

Background:

Compassionate, inclusive, and equitable nursing care begins with integrating concepts of diversity, equity, and inclusion (DEI) and social determinants of health (SDOH) into curricula.

Problem:

Little is known about RN to BSN students' perception of applying these concepts in practice. The purpose of this pilot project was to assess RN to BSN students' perceptions of DEI-SDOH curricular threads in their nursing practice.

Approach:

Students were surveyed to assess their perceptions about the impact DEI-SDOH curricular content had on their ability to assess and address DEI-SDOH in practice, level of confidence in talking about DEI-SDOH, addressing breaches in DEI, and the influence of DEI-SDOH in nursing.

Outcomes:

Respondents indicated DEI-SDOH curricula promoted self-examination, critical examination of health care systems, and increased DEI-SDOH competence.

Conclusion:

DEI-SDOH curricula build upon professional experiences, strengthen assessment and application competence, and equip nurses with confidence to address DEI-SDOH as an effective strategy to reduce health disparities.
Medical and Surgical Management of the Failed Pancreas Transplant
Authors: Casey Michael J. , Murakami Naoka , Ong Song , Adler Joel T. , Singh Neeraj , Murad Haris , Parajuli Sandesh , Concepcion Beatrice P. , Lubetzky Michelle , Pavlakis Martha , Woodside Kenneth J. , Faravardeh Arman , Basu Arpita , Tantisattamo Ekamol , Aala Amtul , Gruessner Angelika C. , Dadhania Darshana M. , Lentine Krista L. , Cooper Matthew , Parsons Ronald F. , Alhamad Tarek
Published: December 2023

Despite the continued improvements in pancreas transplant outcomes in recent decades, a subset of recipients experience graft failure and can experience substantial morbidity and mortality. Here, we summarize what is known about the failed pancreas allograft and what factors are important for consideration of retransplantation. The current definition of pancreas allograft failure and its challenges for the transplant community are explored. The impacts of a failed pancreas allograft are presented, including patient survival and resultant morbidities. The signs, symptoms, and medical and surgical management of a failed pancreas allograft are described, whereas the options and consequences of immunosuppression withdrawal are reviewed. Medical and surgical factors necessary for successful retransplant candidacy are detailed with emphasis on how well-selected patients may achieve excellent retransplant outcomes. To achieve substantial medical mitigation and even pancreas retransplantation, patients with a failed pancreas allograft warrant special attention to their residual renal, cardiovascular, and pulmonary function. Future studies of the failed pancreas allograft will require improved reporting of graft failure from transplant centers and continued investigation from experienced centers.
Relationship of Social Deprivation Among Living Kidney Donor–Recipient Pairs
Authors: Bilen Yara , Schold Jesse D. , Arrigain Susana , Buchalter R. Blake , Huml Anne M.
Published: December 2023

Background.

Living kidney transplant is the most effective renal replacement therapy for patients with end-stage kidney disease. Community-level factors contribute to pervasive socioeconomic and racial disparities in access to living donor kidney transplantation. Little is known about social and environmental conditions between living donors and recipients. Further understanding of these relationships may enhance opportunities for transplantation.

Methods.

From 2010 to 2020, 59 575 living kidney donor–recipient pairs (≥18 y old) were identified using the Scientific Registry of Transplant Recipients. Living donors and recipients were geocoded to area-level social deprivation index (SDI). The primary outcome was difference between recipient and donor SDI. We used multivariable logistic regression to examine recipient and donor characteristics association with residence in different SDI communities.

Results.

Living kidney donation occurs across all strata of social deprivation; including when donors, recipients or both reside in more disadvantaged communities. Donor–recipient race combination and biological relationship are associated with differences in SDI. When compared with White recipients of White donors, Black and Hispanic recipients were more likely to reside in more disadvantaged areas (odds ratio = 2.41 [2.19-2.66] and 1.97 [1.78-2.19]). Recipients in anonymous and paired donations were more likely to reside in areas of more disadvantage than their donors (odds ratio = 1.27 [1.15-1.40] and 1.32 [1.23-1.41] compared with biological); attenuating socioeconomic disparities in access to living donor transplantation.

Conclusions.

Findings illustrate the social and environmental relationships between living kidney donor–recipient pairs that are important to develop targeted approaches and address barriers to living kidney transplantation. Best practices from areas of high deprivation with successful living kidney transplantation can be shared.
Early Metabolic Measures Predict Long-term Insulin Independence in Recipients of Total Pancreatectomy and Islet Autotransplantation
Authors: Nanno Yoshihide , Hodges James S. , Freeman Martin L. , Trikudanathan Guru , Schwarzenberg Sarah J. , Downs Elissa M. , Ramanathan Karthik , Pruett Timothy L. , Beilman Gregory J. , Chinnakotla Srinath , Hering Bernhard J. , Bellin Melena D.
Published: December 2023

Background.

Although diabetes after total pancreatectomy and islet autotransplantation (TP-IAT) is one of the biggest concerns for TP-IAT recipients and physicians, reliable prediction of post-TP-IAT glycemic control remains unestablished. This study was conducted to identify early predictors of insulin independence and goal glycemic control by hemoglobin A1c (HbA1c) ≤ 6.5% after TP-IAT.

Methods.

In this single-center, retrospective study, patients who underwent TP-IAT (n = 227) were reviewed for simple metabolic markers or surrogate indices of β-cell function obtained 3 mo after TP-IAT as part of standard clinical testing. Long-term metabolic success was defined as (1) insulin independence and (2) HbA1c ≤ 6.5% 1, 3, and 5 y after TP-IAT. Single- and multivariate modeling used 3-mo markers to predict successful outcomes.

Results.

Of the 227 recipients, median age 31 y, 30% male, 1 y after TP-IAT insulin independence, and HbA1c ≤ 6.5% were present in 39.6% and 72.5%, respectively. In single-predictor analyses, most of the metabolic markers successfully discriminated between those attaining and not attaining metabolic goals. Using the best model selected by random forests analysis, we accurately predicted 1-y insulin independence and goal HbA1c control in 77.3% and 86.4% of the patients, respectively. A simpler “clinically feasible” model using only transplanted islet dose and BETA-2 score allowed easier prediction at a small accuracy loss (74.1% and 82.9%, respectively).

Conclusions.

Metabolic testing measures performed 3 mo after TP-IAT were highly associated with later diabetes outcomes and provided a reliable prediction model, giving valuable prognostic insight early after TP-IAT and help to identify recipients who require early intervention.
Evaluation of mycotoxins in grains sold in Idah, Ajaka and Ogbogbo areas of Nigeria
Authors: Ukwuru M.U. , Muritala A.
Published: December 2023

Mycotoxin contamination in grains is a significant concern due to its adverse effects on human and animal health. Understanding the levels and patterns of mycotoxin contamination in different regions and storage conditions is crucial for developing effective control strategies. This study aimed to assess mycotoxin levels in stored and recently harvested grains in three regions (Idah, Ajaka, and Ogbogbo) and investigate the implications for food safety. The study involved the analysis of mycotoxin levels in maize, rice, sorghum, and millet using appropriate mycotoxin extraction method based on the mycotoxins of interest and a suitable HPLC system. The findings revealed the presence of mycotoxins such as aflatoxins (1±0.2–5±0.4 µg kg−1), deoxynivalenol (520±0.8–700±1.2 µg kg−1), zearalenone (200±0.4–370±0.6 µg kg−1), ochratoxins (2±0.2–4±0.3 µg kg−1), and fumonisin (0±0.0–4±0.3 µg kg−1) in both recently harvested and stored grains. Patulin was absent in most of the samples. Variations in mycotoxin levels were observed among different grains and regions, highlighting the need for targeted interventions. The European Commission mycotoxin standards in grains for human consumption are: aflatoxins 4 µg kg−1 in maize, millet and sorghum while rice is 8 µg kg−1, deoxynivalenal 1750 µg kg−1, zearalenone 100 µg kg−1, ochratoxin A 5 µg kg−1 for maize, rice and millet, then 10 µg kg−1 for sorghum. Fumonisin is 4000 µg kg−1 but no level for rice and patulin is 50 µg kg−1 for rice and none for the other grains. This study demonstrates the persistence of mycotoxin contamination in stored grains and the importance of considering specific crop types and geographical locations when addressing mycotoxin contamination. The findings underscore the significance of implementing effective control measures to mitigate mycotoxin contamination and enhance food safety. The study provides valuable insights into mycotoxin contamination and emphasizes the need for comprehensive risk assessment studies and appropriate regulatory measures.
Safety and efficacy of orally administered full-spectrum medicinal cannabis plant extract 0.08% THC (NTI-164) in children with autism spectrum disorder: An open-label study
Authors: El-Sukkari Dima , Sharma Kanan , Fleiss Bobbi , Braganza Dion L. , Crichton Alison , Fahey Michael C.
Published: December 2023

Autism spectrum disorder (ASD) is commonly associated with debilitating comorbidities impacting the well-being of affected children and their families. Some children with ASD experience behavioural difficulties that do not respond well to current medications and may also experience unwanted side effects. Therefore, it is crucial to develop alternative, safe and effective therapies. The improved understanding of the endocannabinoid system, together with emerging evidence for the therapeutic effects of cannabis derivatives in neurodevelopment disorders, has led to an exploration of their use in ASD.

This open-label study assessed the efficacy and safety of a novel oil-based full-spectrum medicinal cannabis plant extract 0.08% THC (NTI-164) in treating 14 children with ASD symptoms (13.4 years, range 10-17). Data on the safety profile of NTI-164 was collected through biochemical analysis, vital signs, and parent and participant reports. The efficacy was assessed through a dose-escalation protocol using a broad range of validated clinical behavioural assessments and parent and child-reported questionnaires.

Following four weeks of treatment with NTI-164, 93% of participants demonstrated significant overall improvement in ASD-related symptoms compared to baseline with transient side effects that did not interfere with their general functioning. In addition, targeted behavioural problems were rated as much improved or very much improved in 46% of the treated patients. More than half of caregivers and children also reported decreased anxiety symptoms.

The findings from this study suggest that NTI-164 is well-tolerated and safe, with potential clinical benefits in improving disruptive behaviours and reducing anxiety in children with ASD-related symptoms. Future longitudinal and well-controlled studies are warranted to develop evidence-based clinical therapies and further evaluate the therapeutic benefit of full- spectrum cannabis extracts in managing ASD core and associated comorbid symptoms in this group of children.

Trial registration numberACTRN12621000760875
The immunosuppressive Tuberculosis-associated microenvironment inhibits viral replication and promotes HIV-1 latency in CD4+ T cells
Authors: Cronin Samantha , de Vries-Egan Anneke , Vahlas Zoï , Czernikier Alejandro , Melucci Claudia , Gerber Pehuén Pereyra , O’Neil Thomas , Gloss Brian , Sharabas Mayssa , Turk Gabriela , Verollet Christel , Balboa Luciana , Palmer Sarah , Duette Gabriel
Published: December 2023

Author Summary

Mycobacterium tuberculosis(Mtb), the causative agent of tuberculosis (TB), is the most common coinfection among people living with HIV-1. This coinfection alters the efficacy of the immune response against both HIV-1 andMtb, and is associated with accelerated HIV-1 disease progression and reduced survival. Enhanced HIV-1 replication in macrophages induced byMtbcoinfection may contribute to the worsened clinical outcomes observed in HIV-1/TB coinfected individuals. However, the impact of the HIV-1/TB coinfection on HIV-1 replication and latency in CD4+ T cells remains poorly studied.

In this study, we used the acellular fraction of tuberculous pleural effusion (TB-PE) as a proxy for the microenvironment generated byMtbinfection. Using this physiologically relevant fluid, we investigated whether viral replication and HIV-1 latency in CD4+ T cells are affected by a TB-associated microenvironment. Interestingly, our results revealed that TB-PE shaped the transcriptional profile of CD4+ T cells impairing T cell receptor-dependent cell activation and decreased HIV-1 replication. Moreover, this immunosuppressive TB microenvironment promoted viral latency and inhibited HIV-1 reactivation in CD4+ T cells from people living with HIV-1. This study indicates that the immune response induced by TB may contribute to the persistence of the viral reservoir by silencing HIV-1 expression in individuals coinfected with both pathogens, allowing the virus to persist undetected by the immune system and increasing the size of the HIV-1 latent reservoir in cells at the site of the coinfection.
Predictors of abnormal Thompson score in term neonates in a tertiary hospital in Zimbabwe
Authors: Khan N. , Mugwagwa E. , Cortina-Borja M. , Catherall E. , Fitzgerald F. , Chimhuya S. , Chimhini G. , Gannon H. , Crehan C. , Mangiza M. , Heys M.
Published: December 2023

Background

Neonatal encephalopathy, abnormal neurological function in a baby born at term is a key cause of neonatal death. In the absence of adequate training and brain imaging or monitoring in low-resource settings, clinical risk scores, such as Thompson score, have been useful to predict risk of neonatal encephalopathy. A clearer understanding of the clinical and maternal predictors of abnormal values of Thompson score would be beneficial to identify term neonates with suspected neonatal encephalopathy.

Methods

A scoping review of the literature identified a set ofa priorineonatal and maternal variables associated with neonatal encephalopathy in low-resource settings. Next, a prospective study of all neonates born at term admitted to Sally Mugabe Central Hospital in Zimbabwe between October 2020 and December 2022 (n=6,054) was conducted. A predictive statistical model for abnormal (>10) Thompson score (range 0-22) was developed.

Results

In total 45 articles were identified from three databases and 10 articles were selected. 45 candidate predictors were identified −36 from the available literature and 9 from clinical data and experience. 4.06% (n=246) of neonates had an abnormal Thompson score of 10 or more on admission and 90.65% (n=223) of these neonates had an Apgar score less than 7 at 5 mins (p<0.001). 24 possible predictors were selected as the most important of which nine factors were identified as the most useful in predicting which neonates are at risk of abnormal Thompson score. These predictors and their adjusted odds ratios are: low Apgar score at 5min (OR= 0.46, 95%CI=(0.42, 0.51)), low neonatal heart rate at admission (OR=0.977, 95%CI=(0.97, 0.985)), temperature lower than 36.5°C (OR=1.64, 95%CI=(1.18, 2.28)), abnormal head shape (OR=2.12, 95%CI=(1.51, 2.97)), resuscitation received (OR=3.95, 95%CI=(1.69, 11.01)), neonatal encephalopathy as an admission reason (OR= 2.47, 95%CI=(1.37, 4.32)), risk factors of sepsis other than premature rupture of membrane and offensive liquor (OR=2.04, 95%CI=(1.1, 3.67)), respiratory distress as an admission reason (OR=2.48, 95%CI=(1.59, 3.96)), and other admission reasons (OR=1.81, 95% CI=(1.12, 2.97)). The main admission reasons in ‘Other’ category include low birthweight, meconium aspiration and hypoxic ischaemic encephalopathy and congenital abnormality.

Conclusion

In resource-poor settings where it may be not possible to clinically assess all admitted neonates, those with the identified risk factors should be prioritised for a Thompson score assessment. Local clinical guidelines should incorporate these factors into the clinical management of at-risk neonates and assess their impact on clinical care and neonatal outcomes.
Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL
Authors: Zhao Yaqi , Short Nicholas J , Kantarjian Hagop M , Chang Ti-Cheng , Ghate Pankaj S , Qu Chunxu , Macaron Walid , Jain Nitin , Thakral Beenu , Phillips Aaron H , Khoury Joseph , Garcia-Manero Guillermo , Zhang Wenchao , Fan Yiping , Yang Hui , Garris Rebecca S , Nasr Lewis F , Kriwacki Richard W , Roberts Kathryn G , Konopleva Marina , Jabbour Elias J , Mullighan Charles G
Published: December 2023

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of response to InO. AcquiredCD22mutations were observed in 11% (3/27) of post-InO relapsed tumor samples. There were multipleCD22mutations per sample and the mechanisms of CD22 escape included protein truncation, protein destabilization, and epitope alteration. Hypermutation by error-prone DNA damage repair (alternative end-joining, mismatch repair deficiency) drove CD22 escape. Acquired loss-of-function mutations inTP53,ATMandCDKN2Awere observed, suggesting compromise of the G1/S DNA damage checkpoint as a mechanism of evading InO-induced apoptosis. In conclusion, genetic alterations modulating CD22 expression and DNA damage response influence InO efficacy. The escape strategies within and beyond antigen loss to CD22-targeted therapy elucidated in this study provide insights into improving therapeutic approaches and overcoming resistance.

KEY POINTS

We identified multiple mechanisms of CD22 antigen escape from inotuzumab ozogamicin, including protein truncation, protein destabilization, and epitope alteration.

Hypermutation caused by error-prone DNA damage repair was a driver of CD22 mutation and escape.

VISUAL ABSTRACT