Nevin Manimala

BME Front. 2022 Jul 1;2022:9794321. doi: 10.34133/2022/9794321. eCollection 2022.

ABSTRACT

Objective. Initial performance evaluation of a system for simultaneous high-resolution ultrasound imaging and focused mechanical submillimeter histotripsy ablation in rat brains. Impact Statement. This study used a novel combination of high-resolution imaging and histotripsy in an endoscopic form. This would provide neurosurgeons with unprecedented accuracy in targeting and executing nonthermal ablations in minimally invasive surgeries. Introduction. Histotripsy is a safe and effective nonthermal focused ablation technique. However, neurosurgical applications, such as brain tumor ablation, are difficult due to the presence of the skull. Current devices are too large to use in the minimally invasive approaches surgeons prefer. We have developed a combined imaging and histotripsy endoscope to provide neurosurgeons with a new tool for this application. Methods. The histotripsy component had a 10 mm diameter, operating at 6.3 MHz. Affixed within a cutout hole in its center was a 30 MHz ultrasound imaging array. This coregistered pair was used to ablate brain tissue of anesthetized rats while imaging. Histological sections were examined, and qualitative descriptions of ablations and basic shape descriptive statistics were generated. Results. Complete ablations with submillimeter area were produced in seconds, including with a moving device. Ablation progress could be monitored in real time using power Doppler imaging, and B-mode was effective for monitoring post-ablation bleeding. Collateral damage was minimal, with a 100 μm maximum distance of cellular damage from the ablation margin. Conclusion. The results demonstrate a promising hardware suite to enable precision ablations in endoscopic procedures or fundamental preclinical research in histotripsy, neuroscience, and cancer.

PMID:37850178 | PMC:PMC10521722 | DOI:10.34133/2022/9794321

BME Front. 2022 Oct 25;2022:9786242. doi: 10.34133/2022/9786242. eCollection 2022.

ABSTRACT

The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies, and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this virtual HER2 staining framework was demonstrated by quantitative analysis, in which three board-certified breast pathologists blindly graded the HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs) to reveal that the HER2 scores determined by inspecting virtual IHC images are as accurate as their immunohistochemically stained counterparts. A second quantitative blinded study performed by the same diagnosticians further revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual HER2 staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory and can be extended to other types of biomarkers to accelerate the IHC tissue staining used in life sciences and biomedical workflow.

PMID:37850170 | PMC:PMC10521710 | DOI:10.34133/2022/9786242

BMC Res Notes. 2023 Oct 17;16(1):275. doi: 10.1186/s13104-023-06515-8.

ABSTRACT

OBJECTIVE: In epidemiological and experimental research, high folic acid intake has been demonstrated to accelerate tumor development among populations with genetic and/or molecular susceptibility to cancer. Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder predisposing affected individuals to tumorigenesis, including benign plexiform neurofibromas; however, understanding of factors associated with tumor risk in NF1 patients is limited. Therefore, we investigated whether pregestational folic acid intake modified plexiform-like peripheral nerve sheath tumor risk in a transgenic NF1 murine model.

RESULTS: We observed no significant differences in overall survival according to folate group. Relative to controls (180 days), median survival did not statistically differ in deficient (174 days, P = 0.56) or supplemented (177 days, P = 0.13) folate groups. Dietary folate intake was positively associated with RBC folate levels at weaning, (P = 0.023, 0.0096, and 0.0006 for deficient vs. control, control vs. supplemented, and deficient vs. supplemented groups, respectively). Dorsal root ganglia (DRG), brachial plexi, and sciatic nerves were assessed according to folate group. Mice in the folate deficient group had significantly more enlarged DRG relative to controls (P = 0.044), but no other groups statistically differed. No significant differences for brachial plexi or sciatic nerve enlargement were observed according to folate status.

PMID:37848948 | DOI:10.1186/s13104-023-06515-8

Harm Reduct J. 2023 Oct 17;20(1):150. doi: 10.1186/s12954-023-00888-6.

ABSTRACT

BACKGROUND: Recent policies have lessened restrictions around prescribing buprenorphine-naloxone (buprenorphine) for the treatment of opioid use disorder (OUD). The primary concern expressed by critics of these policies is the potential for buprenorphine diversion. However, the population-level effects of increased buprenorphine diversion are unclear. If replacing the use of heroin or fentanyl, use of diverted buprenorphine could be protective.

METHODS: Our study aim was to estimate the impact of buprenorphine diversion on opioid overdose using an agent-based model calibrated to North Carolina. We simulated the progression of opioid misuse and opioid-related outcomes over a 5-year period. Our status quo scenario assumed that 50% of those prescribed buprenorphine diverted at least one dose per week to other individuals with OUD and 10% of individuals with OUD used diverted buprenorphine at least once per week. A controlled prescription only scenario assumed that no buprenorphine would be diverted, while an increased diversion scenario assumed that 95% of those prescribed buprenorphine diverted and 50% of individuals with OUD used diverted buprenorphine. We assumed that use of diverted buprenorphine replaced the use of other opioids for that day. Sensitivity analyses increased the risk of overdose when using diverted buprenorphine, increased the frequency of diverted buprenorphine use, and simulated use of diverted buprenorphine by opioid-naïve individuals. Scenarios were compared on opioid overdose-related outcomes over the 5-year period.

RESULTS: Our status quo scenario predicted 10,658 (credible interval [CI]: 9699-11,679) fatal opioid overdoses. A scenario simulating controlled prescription only of buprenorphine (i.e., no diversion) resulted in 10,741 (9895-11,650) fatal opioid overdoses versus 10,301 (9439-11,244) within a scenario simulating increased diversion. Compared to the status quo, the controlled prescription only scenario resulted in a similar number of fatal overdoses, while the scenario with increased diversion of buprenorphine resulted in 357 (3.35%) fewer fatal overdoses. Even when increasing overdose risk while using diverted buprenorphine and incorporating use by opioid naïve individuals, increased diversion did not increase overdoses compared to a scenario with no buprenorphine diversion.

CONCLUSIONS: A similar number of opioid overdoses occurred under modeling conditions with increased rates of buprenorphine diversion among persons with OUD, with non-statistical trends toward lower opioid overdoses. These results support existing calls for low- to no-barrier access to buprenorphine for persons with OUD.

PMID:37848945 | DOI:10.1186/s12954-023-00888-6

Neurology. 2023 Oct 17:10.1212/WNL.0000000000207766. doi: 10.1212/WNL.0000000000207766. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Neonatal brain injury is a common and devastating diagnosis conferring lifelong challenges for children and families. The role of mechanical forces applied to the head, often referred to as “birth trauma”, are often considered though evidence for this association is lacking. The objective of this study was to investigate the association between common types of neonatal brain injury and scalp swelling using a novel method to quantify scalp swelling as an unbiased proxy for mechanical forces applied to the head.

METHODS: Case-control study using population-based, prospectively collected tertiary care center databases and healthy controls from the Human Connectome Development Project.

INCLUSION: infants born 32-42 weeks gestational age and MRI in the first 9 days.

OUTCOMES: healthy neonates, hypoxic ischemic encephalopathy (HIE) with or without brain injury, or stroke (ischemic or hemorrhagic). Volume of scalp swelling was objectively quantified by a novel imaging method blinded to brain injury. Variables included mode of delivery and use of instrumentation.

STATISTICAL TESTS: Kruskal-Wallis test, chi square, multivariable and multinomial logistic regression.

RESULTS: There were 309 infants included (55% male): 72 healthy controls, 77 HIE without brain injury on MRI, 78 HIE with brain injury, and 82 with stroke (60 ischemic, 22 hemorrhagic). Scalp swelling was present in 126 (40.8%, 95% CI 35.2-46.5%) with no difference in proportions between outcome groups. Median volume was lower in healthy controls (2.4mL, IQR 1.1-5.6) than those with HIE with brain injury (RRR 1.1, 95% CI 1.05-1.2), HIE without brain injury (RRR 1.1, 95% CI 1.06-1.2) and hemorrhagic stroke (RRR 1.1, 95% CI 1.05-1.2), but not ischemic stroke (RRR 1.1, 95% CI 0.99-1.2). Scalp swelling was associated with instrumented delivery (OR 2.1, 95% CI 1.0-4.1), but not associated with increased odds of brain injury in those with HIE (OR 1.5, 95% CI 0.76-3.30). Scalp swelling measures were highly reliable (ICC=0.97).

DISCUSSION: “Birth trauma” quantified by scalp swelling volume was more common in infants with difficult deliveries but not associated with greater odds of brain injury due to hypoxia or stroke. These results may help parents and practitioners to dissociate the appearance of trauma with the risk of brain injury.

PMID:37848334 | DOI:10.1212/WNL.0000000000207766

Neurology. 2023 Oct 17:10.1212/WNL.0000000000207750. doi: 10.1212/WNL.0000000000207750. Online ahead of print.

ABSTRACT

BACKGROUND: Deep brain stimulation (DBS) of the ventral tegmental area (VTA) is a surgical treatment option for selected patients with refractory chronic cluster headache (CCH). We aimed to identify clinical and structural neuroimaging factors associated with response to VTA DBS in CCH.

METHODS: This prospective observational cohort study examines consecutive patients with refractory CCH treated with VTA DBS by a multidisciplinary team in a single tertiary neuroscience centre as part of usual care. Headache diaries and validated questionnaires were completed at baseline and regular follow up intervals. All patients underwent T1-weighted structural MRI prior to surgery. We compared clinical features using multivariable logistic regression, and neuroanatomical differences using voxel-based morphometry (VBM) between responders and non-responders.

RESULTS: Over a ten-year period, 43 patients (mean age 53 years, SD 11.9), including 29 males, with a mean duration of CCH 12 years (SD 7.4), were treated and followed up for at least one year (mean follow-up duration 5.6 years). Overall, there was a statistically significant improvement in median attack frequency from 140 to 56 per month (Z = -4.95, p <0.001), attack severity from 10/10 to 8/10 (Z = -4.83, p <0.001) and duration from 110 to 60 minutes (Z = -3.48, p <0.001). Twenty-nine (67.4%) patients experienced ≥50% improvement in attack frequency and were therefore classed as responders. There were no serious adverse events. The most common side effects were discomfort or pain around the battery site (seven patients) and transient diplopia and/or oscillopsia (six patients). There were no differences in demographics, headache characteristics, or comorbidities between responders and non-responders. VBM identified increased neural density in non-responders in several brain regions, including the orbitofrontal cortex, anterior cingulate cortex, anterior insula, and amygdala which were statistically significant (p <0.001).

DISCUSSION: VTA DBS showed no serious adverse events, and, although there was no placebo control, was effective in approximately two-thirds of patients at long-term follow up. This study did not reveal any reliable clinical predictors of response. However, non-responders had increased neural density in brain regions linked to processing of pain and autonomic function, both of which are prominent in the pathophysiology of CCH.

PMID:37848331 | DOI:10.1212/WNL.0000000000207750

BMJ Open. 2023 Oct 17;13(10):e074571. doi: 10.1136/bmjopen-2023-074571.

ABSTRACT

INTRODUCTION: The relationship of acute right heart dysfunction (RHD) with long-term cardiopulmonary dysfunction and its’ associated morbidity has not been clearly elucidated. We propose a prospective, observational study to assess the natural history of acute RHD using a combination of imaging, functional and qualitative assessment methods, including the recently described combination of simultaneous maximal effort cardiopulmonary exercise testing and stress echocardiography.

METHODS AND ANALYSIS: We propose a single-centre study of patients ≥18 years admitted to either the intensive care or respiratory close observation units with RHD on transthoracic echocardiography (TTE). Participants will undergo a repeat TTE ~72 hours after the initial study, with a final TTE performed prior to discharge in patients who have a prolonged (>1 week) stay. Inpatient clinical, biochemical and therapeutic indices will be collected contemporaneously. At ~6 months postdischarge, participants will undergo evaluation with validated symptom assessment tools (Dyspnoea-12 and PAH-SYMPACT Questionnaires) and a combined maximal effort cardiopulmonary exercise test and stress echocardiogram. This study is an observational, hypothesis-generating study with a recruitment target of 100 patients established based on typical admission rates of the relevant hospital departments. Measures of central tendency and dispersion will be used to describe the cohort. Inferential statistics will be used to compare the two a priori defined groups of those whose RHD had resolved prior to hospital discharge and those whose dysfunction persisted at time of discharge.

ETHICS AND DISSEMINATION: This study has received ethics approval from the local ethics committee (Nepean and Blue Mountains Local Health District approval, project 2021/ETH12111). Written informed consent will be sought from all patients prior to recruitment. The results will be submitted for publication in a relevant peer-reviewed journal and presented at an appropriate national/international conference.

STUDY REGISTRATION: Australian New Zealand Clinical Trials Registry, ANZCTR12623000309684.

PMID:37848309 | DOI:10.1136/bmjopen-2023-074571

BMJ Open. 2023 Oct 17;13(10):e072187. doi: 10.1136/bmjopen-2023-072187.

ABSTRACT

INTRODUCTION: The goal of this study is to gain firsthand insights from individuals with a history of opioid use disorder (OUD) using medication for OUD on their experiences with postoperative pain care. This study also seeks to describe the experiences of nurses caring for individuals with OUD, and the challenges they may face managing complaints of pain in this population. Research suggests that hospitals can significantly enhance the quality of the care they deliver by investigating an individual’s experience in the care setting. These insights will allow for the development of strategies for nurses to deepen their understanding of and, therefore, advocate and improve care for, this vulnerable and often stigmatised population.

METHODS AND ANALYSIS: A qualitative descriptive study will be conducted consisting of a prescreening and demographics questionnaire, and individual semistructured interviews with approximately 10-15 individuals with OUD having recently undergone surgery and 10-15 nurses providing care for this population for a total of 20-30 interviews. This approach involves the collection of separate but complementary data (ie, perceptions of individuals with OUD and nurses) concerning the phenomena of postoperative pain management. Sampling will continue until data saturation is reached. Descriptive statistics and thematic analysis will then be used. Reporting will adhere to the Standards for Reporting Qualitative Research checklist.

ETHICS AND DISSEMINATION: This study received approval from the Institutional Review Board at Northeastern University. Alongside peer-reviewed journal publications, the findings will be presented at relevant conferences, and a plain language summary will be distributed to the study participants.

PMID:37848308 | DOI:10.1136/bmjopen-2023-072187

BMJ Open. 2023 Oct 17;13(10):e072462. doi: 10.1136/bmjopen-2023-072462.

ABSTRACT

OBJECTIVES: To investigate trends in the incidence rate and main indication for revision hip replacement (rHR) over the past 15 years in the UK.

DESIGN: Repeated national cross-sectional study from 2006 to 2020.

SETTING/PARTICIPANTS: rHR procedures were identified from the National Joint Registry for England, Wales, Northern Ireland, the Isle of Man and the States of Guernsey. Population statistics were obtained from the Office for National Statistics.

MAIN OUTCOME MEASURES: Crude incidence rates of rHR.

RESULTS: The incidence rate of rHR doubled from 11 per 100 000 adults in 2006 (95% CI 10.7 to 11.3) to a peak of 22 per 100 000 adults (95% CI 22 to 23) in 2012, before falling to 17 per 100 000 adults in 2019 (95% CI 16 to 17) (24.5% decrease from peak). The incidence rate of rHR reduced by 39% in 2020 compared with 2019 (during the COVID-19 pandemic). The most frequent indications for rHR between 2006 and 2019 were loosening/lysis (27.8%), unexplained pain (15.1%) and dislocation/instability (14.7%). There were incremental increases in the annual number and incidence rates of rHR for fracture, infection, dislocation/instability and a decrease in rHR for aseptic loosening/lysis.

CONCLUSIONS: The incidence rate of rHR doubled from 2006 to 2012, likely due to high early failure rates of metal-on-metal hip replacements. The incidence of rHR then decreased by approximately 25% from 2012 to 2019, followed by a large decrease during the COVID-19 pandemic. The decrease in the number of rHR performed for aseptic loosening/lysis may reflect improved wear and implant longevity. Increased healthcare resource will be required to care for the increasing numbers of patients undergoing rHR for fracture and infection.

PMID:37848303 | DOI:10.1136/bmjopen-2023-072462

BMJ Open. 2023 Oct 17;13(10):e079407. doi: 10.1136/bmjopen-2023-079407.

ABSTRACT

INTRODUCTION: Preschoolers and school-aged children with congenital heart disease (CHD) are at higher risk of attention deficit hyperactivity disorder (ADHD) compared with the general population. To this day, no randomised controlled trial (RCT) aiming to improve attention has been conducted in young children with CHD. There is emerging evidence indicating that parent-child yoga interventions improve attention and reduce ADHD symptoms in both typically developing and clinical populations.

METHODS AND ANALYSIS: This is a single-blind, two-centre, two-arm trial during which 24 children with CHD and their parents will be randomly assigned to (1) a parent-child yoga intervention in addition to standard clinical care or (2) standard clinical care alone. All participants will undergo standardised assessments: (1) at baseline, (2) immediately post-treatment and (3) 6 months post-treatment. Descriptive statistics will be used to estimate the feasibility and neurodevelopmental outcomes. This feasibility study will evaluate: (1) recruitment capacity; (2) retention, drop-out and withdrawal rates during the yoga programme and at the 6-month follow-up; (3) adherence to the intervention; (4) acceptability of the randomisation process by families; (5) heterogeneity in the delivery of the intervention between instructors and use of home-based exercises between participants; (6) proportion of missing data in the neurodevelopmental assessments and (7) SD of primary outcomes of the full RCT in order to determine the future appropriate sample size.

ETHICS AND DISSEMINATION: Ethical approval has been obtained by the Research Ethics Board of the Sainte-Justine University Hospital. The findings will be disseminated in peer-reviewed journals and conferences and presented to the Canadian paediatric grand round meetings.

TRIAL REGISTRATION NUMBER: NCT05997680.

PMID:37848299 | DOI:10.1136/bmjopen-2023-079407