bluuebunny/crossref_metadata_2025 huggingface dataset:
Vertebral artery dissection with cerebellar infarction due to sudden head turning: A case report
Authors: Huang Yu-Ting , Ou Chien-Yu
Published: June 2024

A 27-year-old man upon quickly turning his head experienced sudden dizziness, unilateral limb weakness, neck pain, and paralysis. He was transported to the emergency department by ambulance. Computed tomography, computed tomography angiography, and magnetic resonance imaging of the brain identified a left vertebral artery dissection with cerebellar infarction without subarachnoid hemorrhage. The patient's blood pressure was controlled, and he was placed on bed rest, but no surgical intervention was undertaken. A cerebral angiography performed 2 months after the dissection found the previously stenosed site fully patent with no further stenosis. Our case suggests that for extracranial vertebral dissection, the patient must be first checked for intracranial subarachnoid hemorrhage, and in its absence, conservative treatment can be considered. Many studies have examined surgical intervention to address vertebral artery dissection; however, our case report presents a literature review regarding suitability for surgery in these patients.
Aortic Valve Thrombus, Stroke, and Endovascular Thrombectomy in a Child With APML and Trisomy 21
Authors: Plant Gayathri , Kirton Adam , Guilcher Gregory M.T. , AlNajjar Mohammad , Mah Kandice , Mitha Alim P. , Riva-Cambrin Jay , Steele MacGregor
Published: June 2024

APML, a subtype of acute myeloid leukemia, is highly curable, with cure rates over 90%. Despite its therapeutic success, APML poses elevated bleeding risks due to frequent prior disseminated intravascular coagulation. Less commonly recognized but critical is the thrombotic risk. We document a unique pediatric case: a 13-year-old with trisomy 21 diagnosed with APML had an asymptomatic aortic valve thrombus leading to thromboembolic arterial ischemic stroke. Through endovascular thrombectomy, cerebral circulation was re-established, extracting a fibrin thrombus with APML cells. Neurological recovery was swift. This report underscores the importance of vigilance for thrombotic complications in APML, highlighting the potential severity of overlooked risks.
Benefits and Barriers of Using Virtual Reality in Teaching Undergraduate Nursing Students
Authors: George Ragi , Titus Sharon K.
Published: June 2024

Background:

Although studies have been conducted using virtual reality (VR) in nursing education, evidence distinguishing the benefits and barriers of adopting VR pedagogical methods to teach undergraduate nursing students is not well-defined in nursing literature.

Purpose:

To identify current evidence on the benefits and barriers of adopting VR as a pedagogical method in nursing education.

Methods:

A scoping review of 6 databases using PRISMA-ScR reporting guidelines. Data were managed using Covidence® software. Table of Evidence illustrates the themes.

Results:

Seventeen articles identified 5 thematic benefits of VR (knowledge acquisition, student engagement, improved self-confidence, teaching strategy, and cost factors) and 4 barriers (physical discomfort, learning outcome challenges, challenges to integrating into curricula, and technology challenges).

Conclusions:

VR is an effective teaching-learning strategy to reinforce nursing concepts and build competencies. It is not a substitute for clinical education.
Defining Nurse Practitioner Core Entrustable Professional Activities
Authors: Moore Jeanne , Chan Tracey , Doucette Julianne , Lipps Terri , Slager Dianne
Published: June 2024

Background:

Gaps between educational preparation and clinical practice readiness have led to innovative approaches to competence assessment. Entrustable professional activities (EPAs) show promise as a competence assessment framework in graduate nursing education.

Purpose:

This study sought to develop and validate a set of EPAs that reflect the core activities performed by all nurse practitioners (NPs).

Methods:

Eight EPAs were developed. A Delphi approach was used to validate the EPAs by NP practice experts located across the United States and representing most NP populations.

Results:

Consensus was reached after 2 Delphi rounds.

Conclusions:

The EPAs developed and validated in this study map multiple advanced-level NP competencies to workplace expectations and provide a shared framework for competency-based workplace assessment among NP preceptors from varied health care professions.
Periorbital Outcomes and Vision Risk Stratification in Treacher Collins Syndrome
Authors: Ng Jinggang J , Zhong Anny , Massenburg Benjamin B , Binenbaum Gil , Wu Meagan , Romeo Dominic J , Katowitz William R , Swanson Jordan W , Bartlett Scott P , Taylor Jesse A
Published: June 2024

Background:

We examined ophthalmologic outcomes and periorbital management in patients with Treacher Collins syndrome (TCS).

Methods:

A retrospective cohort study was performed of children with TCS treated from 2009 to 2023 at our center. Demographics and medical history were collected. Primary outcomes were periorbital findings, surgical burden, and visual acuity. Patients were stratified by risk of vision loss based on ophthalmologic findings.

Results:

Among 50 subjects, mean follow-up was 10.5±5.9 years. Periorbital findings included downslanting palpebral fissures (100%), eyelash deficiency (70%), eyelid coloboma (54%), and significant refractive error (50%). Twenty (40%) individuals underwent 86 periorbital procedures, including lateral canthopexy (n=23 operations) and malar/zygomatic reconstruction/augmentation (n=20). Lateral canthopexies accompanied by malar fat grafting were less likely to require reoperation (0% versus 72%, p=0.004). Subjects with eyelid coloboma were more likely to have exposure keratopathy (30% versus 4%, p=0.020). Grouped by risk of vision loss, 58% were “High” risk, 18% were “Moderate”, and 24% were “Low”. Among 78 eyes of 39 subjects, vision was “Good” in 90%, “Fair” in 5%, and “Poor” in 6%. Vision risk grading was associated with visual acuity outcomes (n=29) (p=0.050).

Conclusions:

In assessing long-term ophthalmological outcomes, we noted good vision despite significant periorbital anomalies. Though most eyelid colobomas can be managed with lubrication, those threatening corneal integrity should be repaired in infancy. As timely intervention may prevent visual impairment, we recommend perinatal ophthalmologist evaluation for all children with TCS. Our proposed vision risk scale may serve as a helpful paradigm by which to contemplate vision-related issues.
Neuropathic Pain after Major Limb Amputation: A Cross-Sectional Study
Authors: Langeveld Mirte , Raasveld Floris V. , Hundepool Caroline A. , Hagenaars Tjebbe , Spijkerman Dorien C. M. , Eberlin Kyle R. , Zuidam J. Michiel
Published: June 2024

Background:

Residual limb pain (RLP) and phantom pain can arise following amputation and may require additional treatment or surgery. This study aimed to determine the prevalence of neuropathic RLP following limb amputation and identify prognostic factors for the development of neuropathic RLP.

Methods:

A cross-sectional study was performed of patients who underwent upper or lower extremity amputation between 1990 and 2021 with a minimum of 12 months’ follow-up. The primary outcome was the prevalence of neuropathic RLP, defined as a 0 to 10 numeric rating analog scale pain score in the residual limb of greater than or equal to 4, in combination with a score greater than or equal to 4 on the short-form Douleur Neuropathic 4 questionnaire, validated for discriminating between nociceptive and neuropathic pain. The secondary outcome was quality of life for amputation patients with and without (neuropathic) RLP. A multivariable linear regression model was used to identify prognostic factors for neuropathic RLP development.

Results:

A total of 121 patients were included: 87 with lower extremity amputations, 29 with upper extremity amputations, and 5 with both. Neuropathic RLP was experienced by 21.5%, whereas 10.7% reported nonneuropathic RLP. Smoking status and complex regional pain syndrome as indications for limb amputation were associated with more severe neuropathic pain symptoms. Patients experiencing neuropathic RLP reported a significantly lower quality of life compared with patients without neuropathic RLP.

Conclusions:

This study demonstrates that neuropathic RLP is common after limb amputation and impacts daily functioning. The absence of numerous manageable prognostic factors associated with neuropathic pain development emphasizes the importance of the consideration of prophylactic interventions at the time of amputation.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Satisfaction with Breasts following Autologous Reconstruction: Assessing Associated Factors and the Impact of Revisions
Authors: Kim Minji , Vingan Perri , Boe Lillian A. , Mehrara Babak J. , Stern Carrie S. , Allen Robert J. , Nelson Jonas A.
Published: June 2024

Background:

Autologous breast reconstruction (ABR) may confer higher patient-reported outcomes than implant breast reconstruction, but an in-depth examination of factors associated with satisfaction after ABR is lacking. The authors aimed to determine independent predictors of 1-year satisfaction with breasts after ABR and assess the importance of elective procedures on satisfaction.

Methods:

A retrospective analysis of patients who underwent abdominally based ABR between 2010 and 2021 and completed the BREAST-Q Satisfaction with Breasts module at 1 year was performed. Elective procedures consisted of breast revision and nipple-areola complex reconstruction.

Results:

A total of 959 patients were included. Satisfaction with Breasts score improved from 53 (interquartile range [IQR], 44 to 64) preoperatively to 64 (IQR, 53 to 78) at 1 year postoperatively (P < 0.001). Factors significantly associated with decreased postoperative score included lower preoperative scores (β = 0.19 [95% CI, 0.08 to 0.31]; P = 0.001), older age (β = −0.17 [95% CI, −0.34 to −0.01]; P = 0.042), Asian race (versus White, β = −6.7 [95% CI, −12 to −1.7]; P = 0.008), and a history of psychiatric diagnoses (β = −3.4 [95% CI, −6.2 to −0.66]; P = 0.015). Patients who received radiation therapy (β = −5.6 [95% CI, −9.0 to −2.3]; P = 0.001) or had mastectomy skin flap/nipple necrosis (β = −3.8 [95% CI, −7.6 to −0.06]; P = 0.046) also had significantly decreased scores. Satisfaction with Breasts scores improved significantly after breast revision procedures (from 54 [IQR, 42 to 65] to 65 [IQR, 54 to 78]; P < 0.001), and nipple-areola complex reconstruction (from 58 [IQR, 47 to 71] to 67 [IQR, 57 to 82]; P < 0.001).

Conclusions:

Multiple independent patient and treatment level factors are associated with lower 1-year Satisfaction with Breasts scores following ABR. Elective procedures have the potential to improve satisfaction. Understanding these findings is imperative for optimizing clinical decision-making and managing expectations.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Left Atrial Strain for Prediction of Left Ventricular Reverse Remodeling After ST-segment Elevation Myocardial Infarction by Cardiac Magnetic Resonance Feature Tracking
Authors: Yang Zhaoxia , Tang Yuanyuan , Sun Wenzhe , Wen Jinyang , Tang Dazhong , Luo Yi , Xiang Chunlin , Huang Lu , Xia Liming
Published: June 2024

Purpose:

The study aimed to investigate the potential utility of left atrial (LA) strain by using cardiac magnetic resonance feature-tracking (CMR-FT) to predict left ventricular reverse remodeling (LVRR) following ST-segment elevation myocardial infarction (STEMI).

Materials and Methods:

Patients with a first STEMI treated by primary percutaneous coronary intervention were consecutively enrolled in the prospective study and underwent CMR scans at 5 days and 4 months. LA global longitudinal strain (reservoir strain [εs], conduit strain [εe], booster strain [εa]) and corresponding strain rate were assessed by CMR-FT using cine images. LVRR was defined as a reduction in the LV end-systolic volume index of >10% from baseline to follow-up. Logistic regression analyses were performed to determine the predictors of LVRR.

Results:

Of 90 patients analyzed, patients with LVRR (n=35, 39%) showed higher values of LA strain and strain rate and less extensive infarct size (IS) compared with patients without LVRR (n=55, 61%) at initial and second CMR. The LVRR group demonstrated significant improvements in LV and LA cardiac function over time, especially the obvious increase in LA strain and strain rate. In multivariate logistic regression analyses, εs and εe, together with IS, were independent predictors of LVRR. The combination of εs and IS could optimally predict the LVRR with the highest area under the curve of 0.743.

Conclusions:

Post-STEMI patients with LVRR presented better recovery from cardiac function and LA deformation compared with patients without LVRR. Assessment of εs and εe by using CMR-FT after STEMI enabled prediction of LVRR.
Discriminative Ability of Dye Injected Into a Meat Model to Determine Accuracy of Ultrasound-Guided Injection
Authors: Brownbridge Regan G. , Kiberd Mathew B. , Werry Daniel , Bailey Jonathan G.
Published: June 2024

Introduction

The utility of using meat models for ultrasound-guided regional anesthesia simulation training has been well established. Feedback is considered the most important element of successful simulation-based education, and simulation offers an opportunity for evaluation. The objective of this study was to establish the discriminative ability of dye injected into a meat model to determine whether injectate is properly placed in the perineural (PN) space, thus providing an additional tool for learner feedback and evaluation.

Methods

Meat models containing a beef tendon (simulating a nerve) were injected with dye in one of 3 locations: PN, intraneural, and intramuscular. Blinded assessors then independently interpreted the dye staining on the models, marked the interpreted injection location, ease of interpretation, and whether staining was present on the beef tendon.

Results

Thirty meat models were injected with dye and independently assessed. Determining the location of injection was deemed to be easy or very easy in 72% of the models. Assessors correctly identified PN, intraneural, and intramuscular injections 100%, 95%, and 85% of the time, respectively. Assessor agreement was 87%.

Conclusions

The location of dye injected into a meat model, simulating a peripheral nerve blockade, can be accurately and reliably scored to provide feedback to learners. This technique offers a novel means of providing feedback to trainees and assessing block success in ultrasound-guided regional anesthesia simulation.
Characteristics and Usefulness of Neurophysiological Monitoring in Corrective Procedures for Abnormally Curved Spine in Young Patients
Authors: Michaeli Avner , Miller Sara , Danto Joseph , Arzi Harel , Schroeder Josh E. , Ovadia Dror
Published: June 2024

Purpose:

To identify and characterize events of deterioration in intraoperative neuromonitoring data during correction procedures for thoracic and lumbar abnormal spinal curvature in young patients.

Methods:

Records of 1,127 cases were retrospectively reviewed to identify events with deterioration of the neuromonitoring data. General etiological and demographic variables were summarized, and neuromonitoring events were studied and characterized.

Results:

Adolescent idiopathic cases were associated with female dominance and older age. Nonadolescent idiopathic cases were associated with a higher rate of neuromonitoring events. The neuromonitoring events evolved during the different procedural stages, were primarily reflected in the motor-evoked potential data and affected a range of neural structures to varying degrees. Most of the events were resolved, partially or completely, following a corresponding intervention by the surgical team, before the end of the procedure. Significant immediate weakness of the lower extremities was demonstrated in patients with unresolved neuromonitoring events, most of them were nonadolescent idiopathic patients.

Conclusions:

Neurophysiological monitoring enables the intraoperative assessment of the integrity of neural pathways and allows the detection of surgery-related impending neural injuries. Neuromonitoring contributes to intraoperative decision making, either when data are uneventful and allow confident continuation or when data deteriorate and lead to corresponding intervention. Further awareness should be paid to the vulnerable characteristics of the patient, surgery course, and neuromonitoring data. Proper interpretation of the neuromonitoring data, together with corresponding intervention by the surgeon when necessary, has the potential to reduce postoperative neurological insults and improve clinical outcomes.
Reflex Responses in Muscles of the Lower Extremities Elicited by Transcutaneous Stimulation of Cauda Equina: Part 1. Methodology and Normative Data
Authors: Rimac Julija , Jančuljak Davor , Kovač Biserka , Jovičić Miloš , Forjan Josipa
Published: June 2024

Introduction:

Transcutaneous electrical stimulation is used to stimulate the dorsal roots of the cauda equina. Multiple elicited responses recorded in the lower extremity muscles are called posterior root muscle reflexes (PRMRs). Normal PRMR values in the muscles of healthy lower extremities have yet to be determined.

Methods:

Thirty subjects without known lumbosacral spinal root illness were included in this study. Subsequently, they were subjected to transcutaneous electrical stimulation of the cauda equina. Posterior root muscle reflex was recorded in the four muscle groups of both lower extremities. We elicited multiple PRMR and examined their characteristics in order to establish normal electrophysiological parameter values.

Results:

Posterior root muscle reflex was successfully elicited in the tibialis anterior (96.7%), gastrocnemius (100%), quadriceps femoris (93.3%), and hamstring (96.7%). No statistically significant differences were found in the intensity of stimulation, latencies, or area under the PRMR between the right and left leg muscles. The area under PRMR varied significantly among the participants. Higher body weight and abdominal girth showed a significant positive correlation with stimulation intensity for eliciting PRMR, and a significant negative correlation with the area under PRMR. Older age showed a significant negative correlation with the success of eliciting PRMR and the area under the PRMR.

Conclusions:

Posterior root muscle reflex is a noninvasive and successful method for eliciting selective reflex responses of cauda equina posterior roots. Obtained values could be used in future studies to evaluate the utility of this methodology in clinical practice. This methodology could improve testing of the proximal lumbosacral nervous system functional integrity.
Adiponectin rescues synaptic plasticity in the dentate gyrus of a mouse model of Fragile X Syndrome
Authors: Thacker Jonathan S. , Bettio Luis , Liang Stanley , Shkolnikov Irene , Collingridge Graham L. , Christie Brian R.
Published: June 2024

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and is the leading known single-gene cause of autism spectrum disorder. Patients with FXS display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently, there is no cure for this condition; however, there is an emerging focus on therapies that inhibit mechanistic target of rapamycin (mTOR)-dependent protein synthesis owing to the clinical effectiveness of metformin for alleviating some behavioural symptoms in FXS. Adiponectin (APN) is a neurohormone that is released by adipocytes and provides an alternative means to inhibit mTOR activation in the brain. In these studies, we show that
Fmr1
knockout mice, like patients with FXS, show reduced levels of circulating APN and that both long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus (DG) are impaired. Brief (20 min) incubation of hippocampal slices in APN (50 nM) was able to rescue both LTP and LTD in the DG and increased both the surface expression and phosphorylation of GluA1 receptors. These results provide evidence for reduced APN levels in FXS playing a role in decreasing bidirectional synaptic plasticity and show that therapies which enhance APN levels may have therapeutic potential for this and related conditions.

This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Contributions of site- and sex-specific LTPs to everyday memory
Authors: Gall Christine M. , Le Aliza A. , Lynch Gary
Published: June 2024

Commentaries about long-term potentiation (LTP) generally proceed with an implicit assumption that largely the same physiological effect is sampled across different experiments. However, this is clearly not the case. We illustrate the point by comparing LTP in the CA3 projections to CA1 with the different forms of potentiation in the dentate gyrus. These studies lead to the hypothesis that specialized properties of CA1-LTP are adaptations for encoding unsupervised learning and episodic memory, whereas the dentate gyrus variants subserve learning that requires multiple trials and separation of overlapping bodies of information. Recent work has added sex as a second and somewhat surprising dimension along which LTP is also differentiated. Triggering events for CA1-LTP differ between the sexes and the adult induction threshold is significantly higher in females; these findings help explain why males have an advantage in spatial learning. Remarkably, the converse is true before puberty: Females have the lower LTP threshold and are better at spatial memory problems. A mechanism has been identified for the loss-of-function in females but not for the gain-of-function in males. We propose that the many and disparate demands of natural environments, with different processing requirements across ages and between sexes, led to the emergence of multiple LTPs.

This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Synapse-specific structural plasticity that protects and refines local circuits during LTP and LTD
Authors: Harris Kristen M. , Kuwajima Masaaki , Flores Juan C. , Zito Karen
Published: June 2024

Synapses form trillions of connections in the brain. Long-term potentiation (LTP) and long-term depression (LTD) are cellular mechanisms vital for learning that modify the strength and structure of synapses. Three-dimensional reconstruction from serial section electron microscopy reveals three distinct pre- to post-synaptic arrangements: strong active zones (AZs) with tightly docked vesicles, weak AZs with loose or non-docked vesicles, and nascent zones (NZs) with a postsynaptic density but no presynaptic vesicles. Importantly, LTP can be temporarily saturated preventing further increases in synaptic strength. At the onset of LTP, vesicles are recruited to NZs, converting them to AZs. During recovery of LTP from saturation (1–4 h), new NZs form, especially on spines where AZs are most enlarged by LTP. Sentinel spines contain smooth endoplasmic reticulum (SER), have the largest synapses and form clusters with smaller spines lacking SER after LTP recovers. We propose a model whereby NZ plasticity provides synapse-specific AZ expansion during LTP and loss of weak AZs that drive synapse shrinkage during LTD. Spine clusters become functionally engaged during LTP or disassembled during LTD. Saturation of LTP or LTD probably acts to protect recently formed memories from ongoing plasticity and may account for the advantage of spaced over massed learning.

This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Interplay of hippocampal long-term potentiation and long-term depression in enabling memory representations
Authors: Hagena Hardy , Manahan-Vaughan Denise
Published: June 2024

Hippocampal long-term potentiation (LTP) and long-term depression (LTD) are Hebbian forms of synaptic plasticity that are widely believed to comprise the physiological correlates of associative learning. They comprise a persistent, input-specific increase or decrease, respectively, in synaptic efficacy that, in rodents, can be followed for days and weeks
in vivo
. Persistent (>24 h) LTP and LTD exhibit distinct frequency-dependencies and molecular profiles in the hippocampal subfields. Moreover, causal and genetic studies in behaving rodents indicate that both LTP and LTD fulfil specific and complementary roles in the acquisition and retention of spatial memory. LTP is likely to be responsible for the generation of a record of spatial experience, which may serve as an associative schema that can be re-used to expedite or facilitate subsequent learning. In contrast, LTD may enable modification and dynamic updating of this representation, such that detailed spatial content information is included and the schema is rendered unique and distinguishable from other similar representations. Together, LTP and LTD engage in a dynamic interplay that supports the generation of complex associative memories that are resistant to generalization.

This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
The plasticity of pyramidal neurons in the behaving brain
Authors: Regele-Blasco Elena , Palmer Lucy M.
Published: June 2024

Neurons are plastic. That is, they change their activity according to different behavioural conditions. This endows pyramidal neurons with an incredible computational power for the integration and processing of synaptic inputs. Plasticity can be investigated at different levels of investigation within a single neuron, from spines to dendrites, to synaptic input. Although most of our knowledge stems from the
in vitro
brain slice preparation, plasticity plays a vital role during behaviour by providing a flexible substrate for the execution of appropriate actions in our ever-changing environment. Owing to advances in recording techniques, the plasticity of neurons and the neural networks in which they are embedded is now beginning to be realized in the
in vivo
intact brain. This review focuses on the structural and functional synaptic plasticity of pyramidal neurons
,
with a specific focus on the latest developments from
in vivo
studies.

This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on'.
Incremental induction of NMDAR-STP and NMDAR-LTP in the CA1 area of ventral hippocampal slices relies on graded activation of discrete NMDA receptors
Authors: Ingram Rachael , Volianskis Rasa , Georgiou John , Jane David E. , Michael-Titus Adina T. , Collingridge Graham L. , Volianskis Arturas
Published: June 2024

N
-methyl-
d
-aspartate receptor (NMDAR)-dependent short- and long-term types of potentiation (STP and LTP, respectively) are frequently studied in the CA1 area of dorsal hippocampal slices (DHS). Far less is known about the NMDAR dependence of STP and LTP in ventral hippocampal slices (VHS), where both types of potentiation are smaller in magnitude than in the DHS. Here, we first briefly review our knowledge about the NMDAR dependence of STP and LTP and some other forms of synaptic plasticity. We then show in new experiments that the decay of NMDAR-STP in VHS, similar to dorsal hippocampal NMDAR-STP, is not time- but activity-dependent. We also demonstrate that the induction of submaximal levels of NMDAR-STP and NMDAR-LTP in VHS differs from the induction of saturated levels of plasticity in terms of their sensitivity to subunit-preferring NMDAR antagonists. These data suggest that activation of distinct NMDAR subtypes in a population of neurons results in an incremental increase in the induction of different phases of potentiation with changing sensitivity to pharmacological agents. Differences in pharmacological sensitivity, which arise due to differences in the levels of agonist-evoked biological response, might explain the disparity of the results concerning NMDAR subunit involvement in the induction of NMDAR-dependent plasticity.

This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Retrospective Characterization of Bone Histomorphometric Findings in Clinical Patient Specimens
Authors: Sellman Linnea , Tong Xiaoyu , Burton Inari S , Kröger Heikki
Published: June 2024

Background: Bone histomorphometry provides comprehensive information on bone metabolism and microstructure. In this retrospective study, we aimed to obtain an overview of the typical indications, referring hospitals, and histomorphometric quantification-based diagnoses of the bone tissue in our histomorphometry laboratory, the only laboratory in Finland carrying out histomorphometric examination of clinical bone biopsies.Methods: Between January 1, 2005 and December 31, 2020, 553 clinical bone biopsies were sent to our histomorphometry laboratory for histomorphometric examination. The median age of the patients was 55 years (range, 0.2–89.9 years), 51% of them were males, and 18% comprised pediatric patients. We received bone biopsy specimens from 23 hospitals or healthcare units. The majority of the samples we sent by nephrologists.Results: The most common bone biopsy indications were suspicion of renal osteodystrophy (ROD), unknown bone turnover status in osteoporosis, and several or untypical fractures. The most common quantitative bone histomorphometry-based diagnosis was ROD. Conclusions: This study provides information on the clinical application of bone histomorphometry in Finland. Precise and quantitative ROD evaluation is the most common indication for bone histomorphometry, being crucial in clinical decision-making and targeted treatment of this patient group.
Two-Year Outcomes of Daily and Twice-Weekly Teriparatide Treatment in Postmenopausal Women with Severe Osteoporosis: A Randomized Non-Blinded Prospective Study
Authors: Mochizuki Takeshi , Yano Koichiro , Ikari Katsunori , Okazaki Ken
Published: June 2024

Background: The long-term effects of daily teriparatide (D-TPTD) and twice-weekly TPTD (W-TPTD) injections are compared among postmenopausal women with severe osteoporosis.Methods: A total of 102 patients were enrolled and randomly allocated into two groups for the administration of either D-TPTD or W-TPTD. Treatment efficacy was measured as the percentage change in bone mineral density (ΔBMD) from baseline in the lumbar spine, total hip, and femoral neck. The findings were compared between the two groups.Results: At 24 months after treatment, the persistence rates and medication possession ratios in the D-TPTD and W-TPTD groups were 68.6% and 56.9%, and 87.8% and 92.0%, respectively. The ΔBMD in the lumbar spine, total hip, and femoral neck were 15.6%±10.2%, 5.3%± 6.3%, and 5.5%±6.2%, respectively, in the D-TPTD group; and 9.5%±7.9%, 2.3%±6.2%, and 3.1%±7.4%, respectively, in the W-TPTD group following 24 months of treatment. The ΔBMD of the lumbar spine (p=0.008) at 24 months and total hip (p=0.024) at 18 months differed significantly between the two groups.Conclusions: D-TPTD administration resulted in a significantly higher BMD in the lumbar spine and total hip, supporting this therapeutic regimen for postmenopausal women with severe osteoporosis.
Exploring the Interplay between Vitamin D, Insulin Resistance, Obesity and Skeletal Health
Authors: Abed Mohammed N. , Alassaf Fawaz A. , Qazzaz Mohannad E.
Published: June 2024

Vitamin D (ViD), plays an important role in calcium absorption and bone mineralization, is associated with bone mineral density. Severe deficiency in ViD has long been linked to conditions such as rickets in children and osteomalacia in adults, revealing its substantial role in skeletal health. Additionally, investigations show an existing interconnection between ViD and insulin resistance (Ins-R), especially in patients with type 2 diabetes mellitus (T2DM). Obesity, in conjunction with Ins-R, may augment the risk of osteoporosis and deterioration of skeletal health. This review aims to examine recent studies on the interplay between ViD, Ins-R, obesity, and their impact on skeletal health, to offer insights into potential therapeutic strategies. Cochrane Library, Google Scholar, and Pubmed were searched to investigate relevant studies until December 2023. Current research demonstrates ViD’s impact on pancreatic β-cell function, systemic inflammation, and insulin action regulation. Our findings highlight an intricate association between ViD, Ins-R, obesity, and skeletal health, providing a perspective for the prevention and/or treatment of skeletal disorders in patients with obesity, Ins-R, and T2DM.
Tocilizumab Reduces Hypercoagulation in COVID-19 – Perspectives from The Coagulation and Immunomodulation Covid Assessment (Coag- ImmCovA) Clinical Trial
Authors: Almskog Lou M. , Sjöström Anna , Sundén-Cullberg Jonas , Taxiarchis Apostolos , Ågren Anna , Freyland Sara , Börjesson Madeleine , Wikman Agneta , Wahlgren Carl Magnus , Wanecek Michael , van der Linden Jan , Antovic Jovan , Lampa Jon , Magnusson Maria
Published: June 2024

Background

Despite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood.

Methods

In this clinical trial conducted in Stockholm, Sweden, interleukin inhibitors, namely anakinra (ANA) or tocilizumab (TOCI), were randomly administered in addition to standard care (SC) to hospitalized patients with COVID-19. A control group received only SC. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential (OHP), visualized through scanning electron microscopy images. Secondary outcomes included effects on conventional coagulation laboratory tests.

Results

The study enrolled 74 patients who were randomized to receive either ANA or TOCI in addition to SC, or SC alone. In the TOCI group, ROTEM variables exhibited less hypercoagulation after 29 days compared with ANA or SC treatment groups, characterized by prolonged clot formation time and decreased clot firmness. OHP decreased, but there were no significant differences among the three treatment groups. Plasma fibrinogen levels, initially elevated, decreased significantly in TOCI recipients over time.

Conclusion

Tocilizumab treatment demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, by improvements in both global coagulation tests and conventional laboratory tests, in comparison with anakinra or SC alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to decrease thrombosis incidence.
Neurophysiology of Resilience in Juvenile Fibromyalgia
Authors: Suñol Maria , Pascual-Diaz Saül , Dudley Jon , Payne Michael , Jackson Catherine , Tong Han , Ting Tracy , Kashikar-Zuck Susmita , Coghill Robert , López-Solà Marina
Published: June 2024

Objective

Juvenile fibromyalgia (JFM) is a chronic pain syndrome predominantly affecting adolescent girls. Resilience may be a protective factor in coping with pain, reducing affective burden, and promoting positive outlooks. Brain regions affected in JFM overlap with those linked to resilience, particularly in the default-mode network (DMN). We investigate the role of resilience on core somatic and affective symptoms in JFM and assess the neurophysiological substrates for the first time.

Methods

Forty-one girls with JFM and 40 pain-free adolescents completed a resting-state fMRI assessment and self-report questionnaires. We used clustering analyses to group JFM participants based on resilience, and principal component analyses to summarize core somatic and affective symptoms. We estimated whole-brain and within-DMN connectivity and assessed differences between higher and lower resilience JFM groups and compared their connectivity patterns to pain-free participants.

Results

The higher resilience JFM group had less affective (T=4.03; p<.001) but similar core somatic symptoms (T=1.05; p=.302) than the lower resilience JFM group. They had increased whole-brain (T’s>3.90, pFDR’s<.03) and within-DMN (T=2.20, p=.03) connectivity strength, and higher connectivity between DMN nodes and self-referential, regulatory, and reward-processing regions. Conversely, higher DMN-premotor connectivity was observed in the lower resilience group.

Conclusion

JFM participants with higher resilience were protected affectively but not in core somatic symptoms. Greater resilience was accompanied by higher signal integration within the DMN, a network central to internally oriented attention and flexible attention shifting. Crucially, the connectivity pattern in highly resilient patients resembled that of pain-free adolescents, which was not the case for the lower resilience group.
Restriction Spectrum Imaging as a quantitative biomarker for prostate cancer with reliable positive predictive value
Authors: Rojo Domingo Mariluz , Do Deondre D , Conlin Christopher C , Bagrodia Aditya , Barrett Tristan , Baxter Madison T , Cooperberg Matthew , Feng Felix , Hahn Michael E , Harisinghani Mukesh , Hollenberg Gary , Javier-Desloges Juan , Kallis Karoline , Kamran Sophia , Kane Christopher J , Kessler Dimitri , Kuperman Joshua , Lee Kang-Lung , Levine Jonathan , Liss Michael A , Margolis Daniel JA , Matthews Ian , Murphy Paul M , Nakrour Nabih , Ohliger Michael , Ollison Courtney , Osinski Thomas , Pamatmat Anthony James , Pompa Isabella R , Rakow-Penner Rebecca , Roberts Jacob L , Santhosh Karan , Shabaik Ahmed S , Song Yuze , Song David , Tempany Clare M. , Wehrli Natasha , Weinberg Eric P. , Woolen Sean , Xu George , Zhong Allison Y , Dale Anders M , Seibert Tyler M
Published: June 2024

Background and Objective

Positive predictive value of PI-RADS for clinically significant prostate cancer (csPCa, grade group [GG]≥2) varies widely between institutions and radiologists. The Restriction Spectrum Imaging restriction score (RSIrs) is a metric derived from diffusion MRI that could be an objectively interpretable biomarker for csPCa.

Methods

In patients scanned for suspected or known csPCa at 7 centers, we calculated patient-level csPCa probability based on maximum RSIrs in the prostate, without relying on subjectively defined lesions. We used area under the ROC curve (AUC) to compare patient-level csPCa detection for RSIrs, ADC, and PI-RADS. Finally, we combined RSIrs with clinical risk factors via multivariable regression, training in a single-center cohort and testing in an independent, multi-center dataset.

Key Findings and Limitations

Among all patients (n=1892), probability of csPCa increased with higher RSIrs . GG≥4 csPCa was most common in patients with very high RSIrs. Among biopsy-naïve patients (n=877), AUCs for GG≥2 vs. non-csPCa were 0.73 (0.69-0.76), 0.54 (0.50-0.57), and 0.75 (0.71-0.78) for RSIrs, ADC, and PI-RADS, respectively. RSIrs significantly outperformed ADC (p<0.01) and was comparable to PI-RADS (p=0.31). The combination of RSIrs and PI-RADS outperformed either alone. Combining RSIrs with PI-RADS, age, and PSA density in a multivariable model achieved the best discrimination of csPCa.

Conclusions and Clinical Implications

RSIrs is an accurate and reliable quantitative biomarker that performs better than conventional ADC and comparably to expert-defined PI-RADS for patient-level detection of csPCa. RSIrs provides objective estimates of probability of csPCa that do not require radiology expertise.
KAN-EEG: Towards Replacing Backbone-MLP for an Effective Seizure Detection System
Authors: Herbozo Contreras Luis Fernando , Cui Jiashuo , Yu Leping , Huang Zhaojing , Nikpour Armin , Kavehei Omid
Published: June 2024

The landscape of artificial intelligence (AI) research is witnessing a transformative shift with the emergence of the Kolmogorov-Arnold Network (KAN), presenting a novel architectural paradigm aimed to redefine the structural foundations of AI models, which are based on Multilayer Perceptron (MLP). Through rigorous experimentation and meticulous evaluation, we introduce the KAN-EEG model, a tailored design for efficient seizure detection. Our proposed network is tested and successfully generalized on three different datasets, one from the USA, one from Europe, and one from Oceania, recorded with different front-end hardware. All datasets are scalp Electroencephalogram (EEG) in adults and are from patients living with epilepsy. Our empirical findings reveal that while both architectures demonstrate commendable performance in seizure detection, the KAN model exhibits high-level out-of-sample generalization across datasets from diverse geographical regions, underscoring its inherent adaptability and efficacy at the backbone level. Furthermore, we demonstrate the resilience of the KAN architecture to model size reduction and shallow network configurations, highlighting its versatility and efficiency by preventing over-fitting insample datasets. This study advances our understanding of innovative neural network architectures and underscores the pioneering potential of KANs in critical domains such as medical diagnostics.
Al-Powered classification of Ovarian cancers Based on Histopathological lmages
Authors: Kussaibi Haitham , Alibrahim Elaf , Alamer Eman , Alhaji Ghada , Alshehab Shrooq , Shabib Zahraa , Alsafwani Noor , Meneses Ritesh G.
Published: June 2024

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Abstract

Background

Ovarian cancer is the leading cause of gynecological cancer deaths due to late diagnosis and high recurrence rates. While histopathological analysis is the gold standard for diagnosis, artificial intelligence (AI) models have shown promise in accurately classifying ovarian cancer subtypes from his-topathology images. Herein, we developed an AI pipeline for automated identification of epithelial ovar-ian cancer (EOC) subtypes based on histopathology images and evaluated its performance compared to the pathologists’ diagnosis.

Methods

A dataset of over 2 million image tiles from 82 whole slide images (WSIs) of the major EOC subtypes (clear cell, endometrioid, mucinous, serous) was curated from public and institutional sources. A convolutional neural network (ResNet50) was used to extract features which were then input to 2 classifiers (CNN, and LightGBM) to predict the cancer subtype.

Results

Both AI classifiers achieved patch-level accuracy (97-98%) on the test set. Furthermore, adding a class-weighted cross-entropy loss function to the pipeline showed better discriminative performance between the subtypes.

Conclusion

AI models trained on histopathology image data can accurately classify EOC subtypes, potentially assisting pathologists and reducing subjectivity in ovarian cancer diagnosis.
Workplace transmission of SARS-CoV-2 among health-care workers in Malaysia
Authors: Chan Yean Yean , Md Zoqratt Muhammad Zarul Hanifah , Lau Nyok-Sean , Musa Nurfadhlina , Khalid Muhammad Fazli , Lim Shu Yong , Wan Mohammad Wan Mohd Zahiruddin , Rahman Sadequr , Eng Wilhelm Wei Han , Hussin Zaini , Muhammad Abdul Haris , Mohd Zain Maizun , Sulaiman Suhaiza , Mohd Fuzi Nik Mohd Hafiz , Mat Salleh Noor Hafizan , Omar Syahida , Halim Ahmad Sukari , Deris Zakuan Zainy , Banga Singh Kirnpal Kaur , Harun Azian , Samsudin Muhammad Nashrul Farhan , Chua Wei Lian , Azmi Nazmi Liana , Engku Abd Rahman Engku Nur Syafirah , Ahmed Naveed , Yaacob Nor Azwany , Hamidun Aliff Ridzwan , Baharuddin Mohd Hazwan , Nik Ab. Kadir Mohd Nasrullah , Hj Mahmud Munira , Suliman Mohd Azmi , Ayub Qasim , Hassan Rosline
Published: June 2024

COVID19 genomic surveillance is instrumental to better understand transmission dynamics in a setting, detect emergence of new variants and monitor spread of variants at the national, regional and global levels. Complete viral genome sequences are powerful enough to approximate epidemiology and enable informed public health response policies and determine their success. Between 24th November to 9th December 2020, a workplace COVID-19 outbreak, assigned as the Hilir cluster, occurred among healthcare workers (HCWs) in a northeast Malaysian university teaching hospital that was not designated for COVID-19 treatment. Mass screening of 1,292 individuals based on case interviews, contact tracings and nucleic acid testing detected 17 cases from various hospital wards and units. To investigate how COVID19 transmission occurred we whole genome sequenced 14 samples collected from healthcare workers and 5 samples from the concurrent community outbreaks. The genomes of these samples were compared with closely-related publically available genomes from GISAID to gain insights into COVID19 transmission in the hospital and at the local and global scale. The 14 viral sequences obtained from the Hilir cluster were assigned to Pango lineages B.1.524 (7 samples) and B.1.36.16 (7 samples) whereas the community samples were assigned as either B.1.524 and B.1. Phylogenetics revealed multiple introduction of B.1.524 into the workplace, while close relatedness of all B.1.36.16 samples suggested that the introduction of these lineages into the workplace likely stemmed from a single introduction. These lines of genomic evidences contradicted with the proposed transmission route, underlining the central role of genomics in COVID-19 or any future pandemics surveillance. The study also highlight the difficulty in enforcing and maintaining isolation methods in a hospital setting.
Rapidly deployable mobile BSL-3 laboratory: A response to nipah virus outbreak in Kozhikode, Kerala, India 2023
Authors: Sahay Rima R. , Patil Deepak Y. , Shete Anita M. , Mohandas Sreelekshmy , Gupta Nivedita , Mourya Devendra T. , Yadav Pragya D.
Published: June 2024

The Nipah virus (NiV) outbreak was declared in Kozhikode district, Kerala state, India on September 12, 2023. The local, state, and national authorities worked in an integrated way to tackle and control the outbreak. Indian Council of Medical Research (ICMR) deployed a team from ICMR-National Institute of Virology (NIV), Pune, India along with an indigenously developed and validated Mobile BSL-3 (MBSL-3) laboratory for providing onsite NiV diagnosis. The Kozhikode district of Kerala state has been an epicenter of three NiV outbreaks in May 2018, August 2021, and recently in September 2023. The Ernakulam district, Kerala also reported NiV outbreak in June 2019. In the 2023 outbreak, six confirmed NiV cases were detected with two deaths. During previous outbreaks in 2019 and 2021, the team from ICMR-NIV, Pune had successfully established the field laboratory utilizing the BSL-2 facility for NiV onsite diagnosis. The BSL-3 personnel protective equipment and standard operative procedures were used to handle the clinical specimens. Post COVID-19 pandemic, under the pioneering initiative of the Government of India, ICMR and Klenzaids Contamination Control Pvt Ltd, Mumbai developed a rapidly deployable, pragmatic, access control and containment laboratory on bus chassis. This MBSL-3 laboratory was utilized for the NiV onsite diagnosis for early containment of outbreak reducing the turnaround time to diagnosis to just 4 hours. MBSL-3 laboratory played a significant role in NiV outbreak response and could be utilized in the future also reaching the remotest areas of the country.