Impact of the COVID-19 Pandemic on Thyroid Cancer Surgery.

The COVID-19 pandemic caused major disruptions to healthcare services in 2020, delaying cancer diagnosis and treatment. While early-stage thyroid cancer often progresses slowly, it is crucial to determine whether treatment delays associated with the pandemic have impacted the clinical presentation and management of advanced-stage thyroid cancer. The purpose of our study was to determine the impact of the early COVID-19 pandemic on thyroid cancer presentation and treatment times. Utilizing the National Cancer Database, chi-squared tests and regression analyses were performed to compare patient demographic and clinical characteristics over time for 56,011 patients diagnosed with primary thyroid cancer who were treated at the Commission on Cancer-accredited sites in 2019 and 2020. We found that thyroid cancer diagnoses decreased between 2019 and 2020, with the biggest drop among patients with cT1 disease relative to other T stages. We also found that patients diagnosed with thyroid cancer in 2020 had similar treatment times to patients diagnosed in 2019, as measured by both the time between diagnosis and start of treatment and the time between surgery and start of radioactive iodine therapy. Overall, our study suggests that resources during the pandemic were allocated to patients with advanced thyroid disease, despite a decrease in diagnoses.

Patient perceptions underlying ctDNA molecular surveillance for HPV(+) oropharyngeal squamous cell carcinoma.

OBJECTIVE: Circulating tumor DNA assays have robust potential as molecular surveillance tools. They may also exacerbate patient distress without improving outcomes. We investigate patient acceptability of a validated ctHPVDNA assay (NavDx) during cancer surveillance for HPV(+) oropharyngeal cancer (OPC). METHODS: Consented HPV(+) OPC participants completed the NCCN Distress Thermometer, the Hospital Anxiety Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) scale both (1) before NavDx blood draw, and (2) after results were provided. Patients then completed a series of focused questions related to their perceptions of the assay. RESULTS: Overall, 55 patients completed the study, with 98.2 % showing no recurrence. For the NCCN Distress Thermometer, median patient distress decreased (2.0 (IQR 1-5) vs. 1.0 (IQR 0-3)) (p < 0.001) in association with NavDx. Using scores ≥ 4 as a cutoff point to define clinically elevated distress, scores also improved (36.4 % vs. 18.2 %, p = 0.031). For HADS, anxiety significantly improved (5.0 (IQR 2.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.037), but not depression (3.0 (IQR 1.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.870). FACT-G scores showed no substantial differences. On survey questionnaires, 95.5 % of patients believed the test to be helpful, and 100 % felt "somewhat" or "extremely" confident in the assay as a monitoring tool. While 59.1 % felt that it reduced anxiety, 88.4 % concordantly felt that it did not introduce anxiety. CONCLUSION: ctHPVDNA as a molecular surveillance tool reduced distress levels in HPV(+) OPC patients, with notably high patient confidence in the approach. Further investigation is warranted to judiciously incorporate this emerging modality in surveillance guidelines.

A Novel Gene Fusion YLPM1::PRKD1 Identified in a Cribriform Subtype of Polymorphous Adenocarcinoma.

Cribriform adenocarcinoma of the salivary gland (CASG) is an entity that is currently classified under polymorphous adenocarcinoma (PAC), cribriform subtype per the 2022 WHO classification of head and neck tumours. There is debate about whether CASG should be considered a separate diagnostic entity, as CASG differs from conventional PAC in anatomic site, clinical behaviors, and molecular patterns. Herein we describe a challenging and unique case which shares histologic and behavioral features between CASG and conventional PAC with a YLPM1::PRKD1 rearrangement not previously reported in the literature.

Ultrarapid Development of Ruptured Esophageal Varices in a Patient With a History of Heller Myotomy.

Esophageal varices commonly affect cirrhotic patients as a result of elevated portal system resistance. Blood pools within esophageal portosystemic collateral vessels, which can eventually rupture, leading to life-threatening hemorrhage. To prevent this, cirrhotic patients without a history of varices undergo endoscopic surveillance for varices every 2-3 years. We present an unusual case of variceal hemorrhage in a patient who was seen to have no varices on endoscopic evaluation only a month earlier.

COVID-19 outcome trends by vaccination status in Canada, December 2020-January 2022.

Background: The coronavirus disease 2019 (COVID-19) pandemic in Canada has evolved rapidly. Since late 2020, COVID-19 vaccines have been relied on to protect against severe outcomes in the presence of circulating variants of concern (VOC). Objective: This surveillance report provides a retrospective descriptive analysis of national trends in COVID-19 cases and severe outcomes by vaccination status, contextualizing trends against case demographics and circulating VOCs, from December 2020 to January 2022. Methods: Case and vaccination coverage surveillance data were obtained from the National COVID-19 Case Dataset and the Canadian COVID-19 Vaccination Coverage Surveillance System for 12 of 13 provinces and territories. Descriptive analyses were produced to describe trends over time among individuals aged 12 years and older by COVID-19 outcome, vaccination status, and demographics. Age-standardized and age-stratified incidence rates and incidence rate ratios were computed for cases, hospitalizations, and deaths. Results: From mid to late-2021, incidence rates for cases and severe outcomes were consistently lowest among those with a completed primary series and highest among those who were unvaccinated. Unvaccinated individuals were much more likely to be hospitalized or to die compared to those with a completed primary series in all variant periods. Age-specific rates of severe outcomes were consistently highest among those aged 80 years and older across all vaccination statuses. Conclusion: Vaccination remains one of the most important public health interventions, particularly among older adults, to protect against COVID-19 severe outcomes as the pandemic evolves. Routine monitoring of COVID-19 outcomes by vaccination status can identify changes in COVID-19 epidemiology and inform public health action and policy.

Digital Neuropsychology beyond Computerized Cognitive Assessment: Applications of Novel Digital Technologies.

Compared with other health disciplines, there is a stagnation in technological innovation in the field of clinical neuropsychology. Traditional paper-and-pencil tests have a number of shortcomings, such as low-frequency data collection and limitations in ecological validity. While computerized cognitive assessment may help overcome some of these issues, current computerized paradigms do not address the majority of these limitations. In this paper, we review recent literature on the applications of novel digital health approaches, including ecological momentary assessment, smartphone-based assessment and sensors, wearable devices, passive driving sensors, smart homes, voice biomarkers, and electronic health record mining, in neurological populations. We describe how each digital tool may be applied to neurologic care and overcome limitations of traditional neuropsychological assessment. Ethical considerations, limitations of current research, as well as our proposed future of neuropsychological practice are also discussed.

Ultrawide-field fluorescein angiography features in patients with anterior uveitis.

PURPOSE: To evaluate the utility of ultrawide-field fluorescein angiography (UWFFA) in patients with anterior uveitis by investigating the detection of retinal vascular leakage (RVL) and the subsequent implications on disease diagnosis and management. STUDY DESIGN/MATERIALS AND METHODS: Patients, who were referred to the National Eye Institute (NEI) for evaluation of anterior uveitis and underwent UWFFA imaging at the initial visit, were included in this study. The electronic medical records of eligible patients were reviewed. The UWFFA images were assessed for severity of retinal vascular leakage, presence of macular leakage, and optic disc leakage by a two-grader system, and intergrader agreement was calculated using the κ-value. Patients with altered diagnoses and management attributable to UWFFA results were noted. RESULTS: A total of 93 eyes of 63 patients were included in the study. Of 93 eyes, 31 (33.3%) eyes had RVL on UWFFA, with 26 (28.0%) eyes and 5 (5.4%) eyes showing mild and moderate-severe RVL, respectively. Twenty-five (26.9%) eyes showed macular leakage, and 7 (7.5%) eyes showed optic disc leakage. The κ-values ranged from 0.85 - 0.87 indicating excellent intergrader agreement. Of the 31 eyes with RVL, the diagnosis was changed to anterior/intermediate uveitis for 9 (29.0%) eyes and to panuveitis for 4 (12.9%) eyes. Systemic treatment was escalated in 5 patients. CONCLUSION: Our results suggest that UWFFA imaging is useful in detecting subclinical posterior involvement in patients with anterior uveitis. Moreover, UWFFA results in altered diagnosis and treatment approaches in a portion of patients.

Passivating the Background of Living Microbes with a Zwitterionic Peptide for Therapies.

Living microbial therapies have been proposed as a course of action for a variety of diseases. However, problematic interactions between the host immune system and the microbial organism present significant clinical concerns. Previously, we developed a genetically encoded superhydrophilic zwitterionic peptide, termed EKP, to mimic low-immunogenic zwitterionic materials, which have been used for the chemical modification of biologics such as protein and nucleic acid drugs to increase their in vivo circulation time and reduce their immunogenicity. Herein, we demonstrate the protective effects of the EKP polypeptide genetically cloaking the surface of Saccharomyces cerevisiae as a model microbe in both in vitro and in vivo systems. First, we show that EKP peptide cloaking suppresses the interactions between yeast cells and their specific antibodies, thereby illustrating its cloaking behavior. Then, we examine the in vitro interactions between EKP peptide surface cloaked yeast cells and murine macrophage cells, which exhibit phagocytotic behavior in the presence of foreign microbes. Our results indicate that EKP cloaking suppresses macrophage interactions and thus reduces phagocytosis. Furthermore, EKP cloaked yeast cells demonstrate a prolonged circulation time in mice in vivo.

Sinonasal Tumors Masquerading as Invasive Fungal Sinusitis (IFS).

OBJECTIVES: Fungal tissue invasion in the setting of sinonasal malignancy has been rarely described in the literature. Only a handful of studies have discussed cases of suspected chronic and acute IFS (CIFS and AIFS, respectively), having an underlying undifferentiated sinonasal carcinoma, sinonasal teratocarcinosarcoma, and NK/T-cell lymphoma. METHODS: Here, we describe 3 cases of carcinoma mimicking IFS from a single institution. RESULTS: Each of our patients presented with sinonasal complaints as an outpatient in the setting of immunosuppression. Intranasal biopsies consistently were predominated by necrotic debris, with and without fungal elements, ultimately leading to a delay of oncologic care. The final pathologies included NK/T-cell lymphoma and SNEC. All patients were followed by radiation and chemotherapy, with 1 case of mortality. CONCLUSIONS: We aim to emphasize the importance of obtaining viable tissue as pathology specimens as the presence of necrosis with fungal elements may limit the diagnosis and ultimately delay the care of an underlying sinonasal carcinoma.

High Heart Rate Variability Buffers the Effect of Attachment Insecurity on Sleep Quality.

OBJECTIVE: Sleep quality is an important health-protective factor. Psychosocial factors, including attachment orientation, may be valuable for understanding who is at risk of poor sleep quality and associated adverse health outcomes. High attachment anxiety is reliably associated with adverse health outcomes, whereas high attachment avoidance is associated with adverse health outcomes when co-occurring with poor self-regulatory capacity, indexed by heart rate variability (HRV). We examined the associations between attachment anxiety, attachment avoidance, HRV, and sleep quality. METHODS: Using longitudinal data from a sample of 171 older adults measured four times over 1 year ( M = 66.18 years old; 67.83% women), we separated the between-person variance (which we call "trait") and within-person variance (which we call "state") for attachment anxiety, attachment avoidance, and HRV (via the root mean square of successive differences). Sleep quality was measured with the Pittsburgh Sleep Quality Index. RESULTS: Higher trait attachment anxiety was associated with poorer global sleep quality ( B = 0.22, p = .005). Higher state attachment avoidance was associated with poorer sleep quality ( B = -0.13, p = .01), except for those with higher trait HRV. Higher state attachment anxiety was associated with poorer sleep quality ( B = -0.15, p = .002), except for those with higher or mean trait HRV. Higher trait attachment anxiety was associated with poorer sleep quality ( B = -0.31, p = .02), except for those with higher trait HRV. CONCLUSIONS: High trait HRV mitigated the adverse effects of attachment insecurity on sleep quality. Our results suggest that people with high trait HRV had greater self-regulation capacity, which may enable them to enact emotion regulation strategies effectively.

Magnetic Resonance Spectroscopy (MRS) in Alzheimer's Disease.

MRS is a noninvasive technique to measure different metabolites in the brain. Changes in the levels of certain metabolites can be used as surrogate markers for Alzheimer's disease. They can potentially be used for diagnosis, prediction of prognosis, or even assessing response to treatment.There are different techniques for MRS acquisitions including STimulated Echo Acquisition Mode (STEAM) and Point Resolved Spectroscopy (PRESS). In terms of localization, single or multi-voxel methods can be used. Based on current data: 1. NAA, marker of neuronal integrity and viability, reduces in AD with longitudinal changes over the time as the disease progresses. There are data claiming that reduction of NAA is associated with tau accumulation, early neurodegenerative processes, and cognitive decline. Therefore, it can be used as a stage biomarker for AD to assess the severity of the disease. With advancement of disease modifying therapies, there is a potential role for NAA in the future to be used as a marker of response to treatment. 2. mI, marker of glial cell proliferation and activation, is associated with AB pathology and has early changes in the course of the disease. The NAA/mI ratio can be predictive of AD development with high specificity and can be utilized in the clinical setting to stratify cases for further evaluation with PET for potential treatments. 3. The changes in the level of other metabolites such as Chol, Glu, Gln, and GABA are controversial because of the lack of standardization of MRS techniques, current technical limitations, and possible region specific changes. 4. Ultrahigh field MRS and more advanced techniques can overcome many of these limitations and enable us to measure more metabolites with higher accuracy. 5. Standardization of MRS techniques, validation of metabolites' changes against PET using PET-guided technique, and longitudinal follow-ups to investigate the temporal changes of the metabolites in relation to other biomarkers and cognition will be crucial to confirm the utility of MRS as a potential noninvasive biomarker for AD.

Pearls & Oy-sters: KLHL11 IgG Paraneoplastic-Associated Hearing Loss and Rhombencephalitis in a Woman With Metastatic Müllerian Tumor.

Kelch-like protein-11 (KLHL11) immunoglobulin G (IgG) is a recently reported paraneoplastic autoantibody associated with rhombencephalitis, which commonly presents with ataxia, diplopia, vertigo, hearing loss, tinnitus, and gaze palsies. The association of this high-risk paraneoplastic autoantibody with testicular germ cell tumors is widely accepted, but it has not been associated with Müllerian tumors. In this study, we report a woman without a known germ cell tumor presenting with signs and symptoms suggesting autoimmune encephalitis. She was found to have metastatic ovarian serous carcinoma with KLHL11 immunoreactivity on histopathology. This case demonstrates a rare cancer association of KLHL11 IgG-seropositive rhombencephalitis with Müllerian tumor and highlights that this autoantibody can also be detected in female patients. Thus, this case expands on the current knowledge of KLHL11-related autoimmune encephalitis including the paraneoplastic presentation, associated tumor types, and management of this syndrome in women.

A Case Report on a Hybrid Approach to Managing Acute Large Bowel Obstruction Secondary to Spigelian Hernia.

Spigelian hernias are an uncommon type of primary ventral hernia and are defined as a defect in the Spigelian aponeurosis (fascia). Herein, we present an uncommon case of Spigelian hernia to highlight the potential complications of these hernias and the need for surgical management. This is a case report of an 86-year-old gentleman presenting post-fall with an acute rib fracture and an incidental Spigelian hernia seen on a CT trauma pan scan. The Spigelian hernia surgical treatment was planned for elective management due to the anesthetic risks associated with an elderly patient and acute rib fractures. Ultimately, the patient developed a large bowel obstruction secondary to the Spigelian hernia and required emergency operative management to relieve the obstruction. The patient had an uncomplicated recovery following his emergency surgery. This case report highlights the importance of assessing anesthetic risks versus surgical risks when it comes to surgical planning. Clinicians should recognize occult hernias and continue ongoing clinical reviews with a high index of suspicion, as symptoms of Spigelian hernia obstruction might be non-specific.

A Systematic Review of Intervention Trials Utilizing Biomarkers Among Informal Caregivers of People with Alzheimer's Disease & Related Dementias.

Informal caregivers of people with Alzheimer's Disease and Related Dementias (ADRD) experience unique stressors, reduced quality of life, and report poorer health, compared to non-caregivers. Throughout the last thirty years, researchers have developed and tested various psychosocial interventions and their ability to improve caregiver health. Due to an exclusive focus on self-report methods, however, no existing systematic literature reviews specifically examine intervention studies employing biomarkers; this systematic review aims to address this gap in the literature. In each database (PubMed and Web of Science, respectively), a title search was conducted with the following keywords: "alzheimer*" OR "dementia" AND "caregiv*" AND "intervention", followed by a second search using identical keywords except "intervention" was replaced with "program." Study or intervention protocol articles, exclusively qualitative studies, cultural applicability papers, dissemination studies, descriptive articles or program reports, acceptability/feasibility studies, studies utilizing formal caregiving samples, commentaries, review papers, and meta-analyses, erratums/corrections, measure development articles, factor analyses, and case reports were excluded from the final pool of studies. In this systematic review, the findings of 14 studies are summarized, and are organized based on specific types of biomarkers: neuroendocrine, immune, and autonomic physiological. Overall, the review yielded mixed results, which may, in part, be due to differences in the types of interventions tested, as well as differing biomarker measurement, methodology, and analysis. More biobehavioral intervention trials are needed among ADRD caregivers. Including biological parameters as pre- and post-measures can shed insight into the extent to which interventions may help caregivers heal from the stress of caregiving.

Spatial transcriptomics reveal neuron-astrocyte synergy in long-term memory.

Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala is a centre of salience networks that underlie emotional experiences and thus has a key role in long-term fear memory formation1. Here we used spatial and single-cell transcriptomics to illuminate the cellular and molecular architecture of the role of the basolateral amygdala in long-term memory. We identified transcriptional signatures in subpopulations of neurons and astrocytes that were memory-specific and persisted for weeks. These transcriptional signatures implicate neuropeptide and BDNF signalling, MAPK and CREB activation, ubiquitination pathways, and synaptic connectivity as key components of long-term memory. Notably, upon long-term memory formation, a neuronal subpopulation defined by increased Penk and decreased Tac expression constituted the most prominent component of the memory engram of the basolateral amygdala. These transcriptional changes were observed both with single-cell RNA sequencing and with single-molecule spatial transcriptomics in intact slices, thereby providing a rich spatial map of a memory engram. The spatial data enabled us to determine that this neuronal subpopulation interacts with adjacent astrocytes, and functional experiments show that neurons require interactions with astrocytes to encode long-term memory.

Development of a measure for assessing malingered incompetency in criminal proceedings: Denney competency related test (D-CRT).

INTRODUCTION: Experts frequently assess competency in criminal settings where the rate of feigning cognitive deficit is demonstrably elevated. We describe the construction and validation of the Denney Competency Related Test (D-CRT) to assess feigned incompetency of defendants in the criminal adjudicative setting. It was expected the D-CRT would prove effective at identifying feigned incompetence based on its two alternative, forced-choice and performance curve characteristics. METHOD: Development and validation of the D-CRT occurred in described phases. Items were developed to measure competency based upon expert review. Item analysis and adjustments were completed with 304 young teenage volunteers to obtain a proper spread of item difficulty in preparation for eventual performance curve analysis (PCA). Test-retest reliability was assessed with 44 adult community volunteers. Validation included an analog simulation design with 101 jail detainees using MacArthur Competency Assessment Test-Criminal Adjudication and Word Memory Test as criterion measures. Effects of racial/ethnic demographic differences were examined in a separate study of 208 undergraduate volunteers. D-CRT specificity was identified with 46 elderly clinic referrals diagnosed with mild cognitive impairment and dementia. RESULTS: Item development, adjustment, and repeat analysis resulted in item probabilities evenly spread from .28 to 1.0. Test-retest correlation was good (.83). Internal consistency of items was excellent (KR-20 > .91). D-CRT demonstrated convergent validity in regard to measuring competency related information and as well as malingering. The test successfully differentiated between jail inmates asked to perforfm their best and inmates asked to simulate incompetency (AUC = .945). There were no statistically significant differences found in performance across racial/ethnic backgrounds. D-CRT specificity remained excellent among elderly clinic referrals with significant cognitive compromise at the recommended total score cutoff. CONCLUSIONS: D-CRT is an effective measure of feigned criminal incompetency in the context of potential cognitive deficiency, and PCA is assistive in the determination. Additional validation using knowns groups designs with various mental health-related conditions are needed.

Reflections on resilience.

Resilience research has long sought to understand how factors at the child, family, school, community, and societal levels shape adaptation in the face of adversities such as poverty and war. In this article we reflect on three themes that may prove to be useful for future resilience research. First is the idea that mental and physical health can sometimes diverge, even in response to the same social process. A better understanding of explanations for this divergence will have both theoretical and public health implications when it comes to efforts to promote resilience. Second is that more recent models of stress suggest that stress can accelerate aging. Thus, we suggest that research on resilience may need to also consider how resilience strategies may need to be developed in an accelerated fashion to be effective. Third, we suggest that if psychological resilience interventions can be conducted in conjunction with efforts to enact system-level changes targeted at adversities, this may synergize the impact that any single intervention can have, creating a more coordinated and effective set of approaches for promoting resilience in young people who confront adversity in life.

Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial.

INTRODUCTION: Sarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective interventions is in need. Previous studies showed that ß-hydroxy ß-methylbutyrate (HMB) supplement and vibration treatment (VT) enhanced muscle quality, while the coapplication of the two interventions had further improved muscle mass and function in sarcopenic mice model. This study aims to investigate the efficacy of this combination treatment in combating sarcopenia in older people. The findings of this study will demonstrate the effect of combination treatment as an alternative for managing sarcopenia. METHODS AND ANALYSIS: In this single-blinded randomised controlled trial, subjects will be screened based on the Asian Working Group for Sarcopenia (AWGS) 2019 definition. 200 subjects who are aged 65 or above and identified sarcopenic according to the AWGS algorithm will be recruited. They will be randomised to one of the following four groups: (1) Control+ONS; (2) HMB+ONS; (3) VT+ONS and (4) HMB+VT + ONS, where ONS stands for oral nutritional supplement. ONS will be taken in the form of protein formular once/day; HMB supplements will be 3 g/day; VT (35 Hz, 0.3 g, where g=gravitational acceleration) will be received for 20 mins/day and at least 3 days/week. The primary outcome assessments are muscle strength and function. Subjects will be assessed at baseline, 3-month and 6-month post treatment. ETHICS AND DISSEMINATION: This study was approved by Joint CUHK-NTEC (The Chinese University of Hong Kong and New Territories East Cluster) Clinical Research Management Office (Ref: CRE-2022.223-T) and conformed to the Declaration of Helsinki. Trial results will be published in peer-reviewed journals and disseminated at academic conferences. TRIAL REGISTRATION NUMBER: NCT05525039.

Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes.

The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications. Here, we report results generated using a recently streamlined pipeline approach for the evaluation of the effects of chemical compounds on lifespan and health. We studied five compounds previously shown to extend C. elegans lifespan or thought to promote mammalian health: 17α-estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. We found that green tea extract and nordihydroguaiaretic acid extend Caenorhabditis lifespan in a species-specific manner. Additionally, these two antioxidants conferred assay-specific effects in some studies-for example, decreasing survival for certain genetic backgrounds in manual survival assays in contrast with extended lifespan as assayed using automated C. elegans Lifespan Machines. We also observed that GTE and NDGA impact on older adult mobility capacity is dependent on genetic background, and that GTE reduces oxidative stress resistance in some Caenorhabditis strains. Overall, our analysis of the five compounds supports the general idea that genetic background and assay type can influence lifespan and health effects of compounds, and underscores that lifespan and health can be uncoupled by chemical interventions.