Clinical Observations Research Articles

Élever la bizarrerie à la dignité du style. Pour une éthique de l’accompagnement des patients autistes

ObjectivesThis article aims to identify how the analytical framework can lead an autistic subject to create an artisanal solution that allows him to enter the world. MethodThe Lacanian theoretical conceptualization is based on clinical observations collected during the treatment of a young autistic boy. ResultsWe argue that engaging in therapeutic work with an autistic patient can offer him a potential environment – which we distinguish from potential space – in which his particular quirks can be elevated to the dignity of a style that the autistic child will himself shape and that will allow him a certain social bond. DiscussionWe qualify the therapeutic space offered by the analytical framework as a potential environment, which we define as the coordinates of the encounter set up by the clinician bringing into existence a Stimmung from which the child can experience his or her instinctual movements. Stimmung is to be understood as the phenomenological quality of the potential environment, simultaneously including tuning, invocative address, disposition, and atmosphere, i.e. a possible relationship with the Other. Clinical intervention would allow the child not to represent himself in this potential environment – which is the nature of potential space –, but to present himself to the world. It is the clinician's responsibility to bring into existence an Other who can isolate and put into circulation the subject's oddity – which could be considered a failure – bringing forth a singularizing sign and elevating it to the dignity of style that the autistic child will shape. ConclusionThe style, thus obtained, corresponds to the possibility of a singular enunciative position – inscribing a presence in the world by tempering the weight of the subject –, which, in autism, always requires a certain amount of tinkering in order to arrive at a solution.

Cost-effectiveness analysis of routine computed tomography angiography (CTA) for lower extremity penetrating trauma

BackgroundRoutine evaluation with CTA for patients with isolated lower extremity penetrating trauma and normal ankle-brachial-indices (ABI) remains controversial. While prior literature has found normal ABI's (≥0.9) and a normal clinical examination to be adequate for safe discharge, there remains concern for missed injuries which could lead to delayed surgical intervention and unnecessary morbidity. Our hypothesis was that routine CTA after isolated lower extremity penetrating trauma with normal ABIs and clinical examination is not cost-effective. MethodsWe performed a decision-analytic model to evaluate the cost-effectiveness of obtaining a CTA routinely compared to clinical observation and ABI evaluation in hemodynamically normal patients with isolated penetrating lower extremity trauma. Our base case was a patient that sustained penetrating lower extremity trauma with normal ABIs that received a CTA in the trauma bay. Costs, probability, and Quality-Adjusted Life Years (QALYs) were generated from published literature. ResultsClinical evaluation only (no CTA) was cost-effective with a cost of $2056.13 and 0.98 QALYs gained compared to routine CTA which had increased costs of $7449.91 and lower QALYs 0.92. Using one-way sensitivity analysis, routine CTA does not become the cost-effective strategy until the cost of a missed injury reaches $210,075.83. ConclusionsPatients with isolated, penetrating lower extremity trauma with normal ABIs and clinical examination do not warrant routine CTA as there is no benefit with increased costs.

Acute watery diarrhoea cases during cholera outbreak in Syria: a cohort study

ObjectivesThe aim of this study is a descriptive presentation of cases of acute watery diarrhoea (AWD) that were presented to Aleppo University Hospital (AUH) during the recent cholera outbreak in...

Predicting Clinical Pharmacokinetics/Pharmacodynamics and Impact of Organ Impairment on siRNA-Based Therapeutics Using a Mechanistic Physiologically-Based Pharmacokinetic-Pharmacodynamic Model.

Approved and emerging siRNA therapeutics are primarily designed for targeted delivery to liver where the therapeutic gene silencing effects occurs. Impairment of hepatic/renal function and its impact on siRNA pharmacokinetics/pharmacodynamics (PKs/PDs) are yet to be mechanistically evaluated to describe the unanticipated clinical observations for this novel modality. We developed pathophysiologically relevant models for organ impairment within a physiologically-based PK-PD (PBPK-PD) modeling framework focusing on modality-specific mechanistic factors to evaluate impact on siRNA PKs and PDs. PBPK-PD models for two US Food and Drug Administration (FDA) approved siRNAs inclisiran and vutrisiran were developed as case studies leveraging available tissue-specific data and translated to humans. Key determinants of the clinical PK and PD of N-acetylgalactosamine conjugated siRNAs (GalNAc-siRNAs) with varying sequences were also identified to inform effective clinical translation strategies for emerging GalNAc-siRNA candidates. A 30-70% reduction in hepatic asialoglycoprotein receptors concentrations still allowed for sufficient amount of free cytoplasmic siRNA for RISC-loading to produce PD effects comparable in extent and duration to normal liver function. This included severe hepatic impairment for which no clinical data are available. Inclusion of other modality agnostic physiological changes relevant to organ impairment did not alter the findings. Changes in renal physiologies, including changes in GFR across various degrees of impairment, well predicted minimal changes in PD for inclisiran and vutrisiran. This work provides a quantitative mechanistic framework and insights on modality-specific factors that drive clinical translation and patient/disease-related factors that impact specific dosing considerations and clinical outcomes to help accelerate the optimal development of siRNA therapeutics.

Short report: Twins with 20p13 duplication. Case report and comprehensive literature review.

Trisomy 20p is a rare genetic condition caused by a duplication of the short arm of chromosome 20. We employed clinical observation and molecular genetic testing (SNP microarray), to study identical twin males with an unknown dysmorphic syndrome. We conducted a literature review of trisomy 20p and collated the clinical and molecular genetic findings on 20 affected subjects reported since 2000. Identical twin males, whose prenatal course was complicated by a twin-to-twin transfusion, manifested profound language and neurocognitive delays as well as distinctive facial dysmorphisms when evaluated at 2 years of age. SNP microarray identified identical duplications of 20p13 with no other chromosomal aberrations. A literature survey of 20p trisomy syndrome identified 20 other examples of this condition reported since 2000, which we collated with 33 summarized by Sidwell etal. (2000). Within the combined total of 55 affected individuals, we found a distinctive clinical phenotype that provides insight on the effects of abnormal dosage of genes in 20p13. These loci include FAM110A (OMIM 611393), ANGPT4 (OMIM 603705), RSPO4 (OMIM 610573), PSMF1 (OMIM 617858), SNPH (OMIM 604942), SDCBP2 (OMIM 617358), FKBP1A (OMIM 186945), TMEM74B, C20orf202, and RAD21L1 (OMIM 619533). Gene profiling highlighted that syntaphilin (SNPH) is highly expressed in mammalian brain, where it is considered critical for mitochondrial transport in neuronal axons, and to directly influence axonal morphogenesis and function. We propose that abnormal activity of syntaphilin engendered by the trisomy is primarily responsible for the language, neurocognitive, and gross motor delays reported in individuals with 20p trisomy. Additional studies, for example, characterization of cerebral organoids generated from affected patients may help to better understand this condition, and potentially suggest rational remedies to improve the lives of affected individuals and their families.

Breast cancer prognosis through the use of multi-modal classifiers: current state of the art and the way forward.

We present a survey of the current state-of-the-art in breast cancer detection and prognosis. We analyze the evolution of Artificial Intelligence-based approaches from using just uni-modal information to multi-modality for detection and how such paradigm shift facilitates the efficacy of detection, consistent with clinical observations. We conclude that interpretable AI-based predictions and ability to handle class imbalance should be considered priority.

Assessment of the dalargin effect on the level of vitamin D and melatonin in blood serum in patients with malignant bone tumors and polymorbidity

Background. Involved in many cascades of biological regulatory reactions, calcium, vitamin D and melatonin create a single metabolic pattern, maintaining the dynamic balance of bone tissue homeostasis. Nevertheless, these regulatory molecules, as structural and functional elements of bone tissue, play a crucial role in various cellular processes associated with oncogenesis and tumor progression. Synthetic peptide dalargin has wound healing, reparative, anti-inflammatory, antioxidant, immunomodulatory, anticarcinogenic, antitumor, and antimetastatic effects. The purpose of the study was to investigate the synthetic neuropeptide dalargin influence on the dynamics of vitamin D and melatonin blood serum le­vels as part of the treatment algorithm of patients with bone malignant tumors of the lower extremities and pelvis with polymorbidity and endoprosthetics. Materials and methods. The study inclu­ded a control (first) group and a main (second) group of clinical observation of patients with malignant bone lesions. The serum melatonin content was measured by enzyme immunoassay using reagent kits (No. RE54021) from IBL-Hamburg GmbH (Germany). Serum levels of 25-hydroxycalciferol (25(OH)D) were determined by the immunochemiluminescent method on an ARCHITECT 25-OH Vitamin D Controls automatic analyzer. Results. In patients who received dalargin, more pronounced positive dynamics were established in the normalization of 25(ОН)D and melatonin levels, and there was no exacerbation of concomitant diseases. In contrast to the data of patients who did not receive dalargin, in the group where it was used, there were no relapses or metastases of the tumor du­ring 14 months. A comparison of the 25(ОН)D and melatonin le­vels in patients 6–7 months and 12–14 months after treatment shows a tendency to recovery of indicators only in patients who were additionally treated with dalargin (p < 0.01). Conclusions. The study showed the possibility of using the neuropeptide dalargin to increase the effectiveness of the treatment of patients with primary malignant tumors with the burden of polymorbidity by influencing the levels of vitamin D and melatonin in the blood serum.

A case of Brucellosis with neurological and dermatological findings in a thoroughbred Arabian horse

Brucellosis, a zoonotic infection, exhibits varying prevalence across different geographical regions, with a notable incidence in Mediterranean countries, contributing to considerable economic losses. This study focuses on an 11-year-old purebred male Arabian horse, presenting symptoms including weight loss, weakness, environmental indifference, joint swelling, and diverse dermatological manifestations despite sufficient feed intake. A pivotal clinical observation from anamnesis and examination is the animal's inclination to lean its head against walls or fixed objects. In conjunction with hematological and biochemical analyses, the Brucella Rose Bengal plate test (RBPT) and serum agglutination test (SAT) were conducted, revealing seropositivity for brucellosis in the patient. Consequently, it is imperative for professionals in the equine breeding sector, particularly clinical veterinarians, to adhere to biosafety protocols concerning brucellosis cases exhibiting atypical clinical symptoms in horses. Proper diagnostic methods should be employed to assess suspicious cases, underscoring the significance of safeguarding both public and animal health.

СЛУЧАЙ ИЗ ПРАКТИКИ: ЭПИЗОДИЧЕСКАЯ ПАРОКСИЗМАЛЬНАЯ МОЗЖЕЧКОВАЯ АТАКСИЯ 2 ТИПА

Instability walking is a fairly common complaint made by patients who come to be examined by a neurologist in polyclinics and hospitals. From a medical point of view, this symptom is included in the concept of "ataxia". Neurologists distinguish four types of ataxia depending on the localization of the pathological process: cortical, cerebellar, vestibular, and sensitive. There are often combinations of different types of ataxia in the same patient, for example, cortical-vestibular, sensitive-cerebellar. In addition to establishing the variant of the atactic syndrome, there is an urgent question of verifying the etiological factor that led to this pathology. Pathological heredity becomes the least obvious. In this article, we draw attention to a similar case from practice in order to form the alertness of doctors regarding hereditary coordination disorders. Episodic ataxia is a group of rare hereditary diseases of the nervous system, the main clinical manifestation of which are paroxysms of cerebellar ataxia of varying duration and frequency. The most studied from a genetic and clinical point of view are episodic cerebellar ataxia of the first and second types. The authors present a clinical case of episodic paroxysmal cerebellar ataxia type 2 in a 22-year-old patient. The diagnosis of the disease was based on a typical clinical picture and confirmed by a molecular genetic study that revealed a mutation in the CACNA1A gene. The article discusses aspects of the pathogenesis of the main forms of episodic paroxysmal ataxia, age of onset, frequency and duration of seizures, features of the clinical picture, neurological status. This clinical observation draws the attention of practitioners to the possibilities of modern methods of molecular genetic diagnosis and treatment of these conditions.

Establishment of health food safety evaluation method-In vivo genotoxicity evaluation by micronucleus assay

In recent years, various factors such as shifts in health consciousness, changes in lifestyle habits, increased focus on dietary intake, the promotion of alternative medical concepts, and advancements in life sciences and technology have propelled the robust growth of the health food industry. An increasing number of reports suggest that "functional foods," containing beneficial functional components, may enhance short-term well-being and are increasingly regarded as healthful. Building upon these findings, this study aims to enhance the production capacity of high-value agricultural products. However, for quality assurance, toxicity assessment of functional foods is imperative. There is a growing necessity to employ in vivo genotoxicity assays to evaluate the carcinogenic potential of these products. In this study, we tried to establish another in vivo genotoxicity evaluation platform via acridine orange induction. According to all results in this study, during the experiment, there were no statistically significant differences in BW between the negative control group and the normal control group (p > 0.05). Moreover, the clinical observations of the experimental mice showed that all mice survived until the end of the experiment, and no abnormal clinical symptoms were observed. The mouse’s food consumption in each group were monitored during the experiments. The food consumption of mice was recorded daily after the experiment. During the experiments, there were no significant difference between two groups on the food consumption. The percentage of RETs/1,000 RBCs in the negative control group was significantly decrease than the normal control group (p < 0.001). RETs/1,000 RBCs (‰) in ICR mice (n = 5/group) in the negative control group and the normal control group at 48th and 72th hours-experiment were respectively 18 ± 4.6 / 45.6 ± 4.0 (48th hours-experiment) and 19 ± 4.8 / 47.6 ± 4.8 (72th hours-experiment). The percentage of Mn-RETs/1,000 RETs in the negative control group was significantly increase than the normal control group (p < 0.001). Mn-RETs/1,000 RETs (‰) in ICR mice (n = 5/group) in the negative control group and the normal control group were 10.6 ± 2.1 / 0.4 ± 0.5 and 8.2 ± 1.8 / 0.4 ± 0.5, respectively. Taken all results of RET/RBCs (‰) and MN-RET/RETs (‰) together, the genotoxicity in the negative control group has been successfully induced. In light of these requirements, we propose utilizing the mammalian erythrocyte micronucleus assay to detect damage induced by test substances to erythroblast chromosomes. This study endeavors to establish a sensitive and stable method for quantifying micronuclei formation in erythrocytes in vivo. The resulting data will facilitate the evaluation of potential toxicity associated with agricultural functional products in the future.

ESKİ MISIRDA ARTERİOSKLEROZ

Aim; This study was planned to investigate the formation of arteriosclerosis in ancient times. Materials and Methods; The HORUS study, which investigated the vascular structures of mummified people in the ancient Egyptian civilization, was taken as a basis and the results of this study were evaluated with fractional tomography. These results, evaluated with virtual angiography, were evaluated non-parametrically with clinical observations. Results; Various degrees of atherosclerosis were observed in all vascular structures of the examined mummies. Significant mitral annular calcification was detected in one case. Conclusion; In the light of these studies, it was concluded that arthriosclerosis is a disease of all periods.

Beyond the fractures: A comprehensive Comparative analysis of Affordable and Accessible laboratory parameters and their coefficients for prediction and Swift confirmation of pulmonary embolism in high-risk orthopedic patients

BackgroundPulmonary embolism (PE) poses a significant challenge in diagnosis and treatment, particularly in high-risk patient populations such as those hospitalized for orthopedic reasons. This study explores the predictive and diagnostic potential of laboratory parameters in identifying PE among orthopedic patients. ObjectivesThe purpose of this study was to determine whether selected (inexpensive and readily available) laboratory parameters and their coefficients can be used to diagnose pulmonary embolism and whether they are applicable in predicting its occurrence. Material and methodsSelected laboratory parameters were determined twice in 276 hospitalized orthopedic patients with suspected PE: PLT, MPV, NEU, LYM, D-dimer, troponin I, age-adjusted D-dimer and their coefficients. Depending on the angio-CT results, patients were divided into groups. Selected popular laboratory coefficients were calculated and statistically analyzed. Optimal cutoff points were determined for the above laboratory tests and ROC curves were plotted. ResultsD-dimer/troponin I [p = 0.008], D-dimer [p = 0.001], age-adjusted D-dimer [p = 0.007], NLR/D-dimer [p = 0.005] and PLR [p = 0.021] are statistically significant predictors of PE. D-dimer/troponin I [p < 0.001], troponin I [p = 0.005] and age-adjusted D-dimer [p = 0.001] correlated with the diagnosis of PE after the onset of clinical symptoms. ConclusionsIn the context of orthopedic patients, cost-effective laboratory parameters, particularly the D-dimer/troponin I ratio and age-adjusted D-dimer, exhibit considerable potential in predicting and diagnosing PE. These findings suggest that combining readily available laboratory tests with clinical observation can offer a viable and cost-effective diagnostic alternative, especially in resource-constrained settings. Further studies with larger and diverse patient populations are recommended to validate these results.

Duchenne Muscular Dystrophy-Associated Neurobehavioral Difficulties: Insights from Clinical Practice

Background: Emerging evidence underscores the high prevalence of neurobehavioral difficulties like ADHD, ASD and OCD, in patients with Duchenne muscular dystrophy (DMD). The substantial impact of these complex behavioral challenges in addition to motor function decline on the well-being of affected individuals and their families is increasingly evident. However, a uniform approach for effective screening, assessment and management of the neurobehavioral symptoms remains elusive. Objective: We explored strategies used by healthcare professionals with clinical expertise in DMD to address neurobehavioral symptoms, in order to uncover diverse practices and to identify potential directions for clinical approaches in managing DMD neurobehavioral symptoms. Methods and results: Twenty-eight respondents from 16 different countries completed an online survey. Only 35% of the centers systematically screened for neurobehavioral difficulties in their DMD population. Predominant screening methods included history taking and clinical observation. Common neurobehavioral difficulties encompassed learning challenges, dependency from adults, anxiety, concentration difficulties, and social deficits. The participating centers frequently employed parental counseling and liaison with psychosocial healthcare professionals for psychosocial intervention. Conclusion: This study underscores the complex behavioral landscape in DMD, highlighting the need for validated screening, assessment and management strategies and collaborative efforts in implementing these. We advocate for international consensus recommendations for screening, assessment and management of neurobehavioral difficulties in DMD to enhance patient care and communication across healthcare settings.

Variability in Intracranial Vessel Diameters and Considerations for Neurovascular Models: A Systematic Review and Meta‐Analysis

BACKGROUND In vitro experiments are critical for understanding the impact of medical devices and techniques on blood vessels and blood flow. However, their interpretation is often limited by anatomical models’ inability to capture the wide range of vessel sizes observed in real‐world practice. The current study aims to address this limitation by describing the distribution of vessel diameters in a real‐world population. METHODS This systematic literature review using the PubMed database analyzed cerebral vessel diameters in patients from 2000 to 2022. The diameter measurements of various vessels within the neurovasculature were extracted. Random‐effects meta‐analyses were performed to synthesize vessel diameters across studies. Predicted distributions were generated from the meta‐analytical results. RESULTS Seventy‐six studies were included in the analysis. The M1 segment, internal carotid artery (cervical and communicating segments), A1 segment, V2 segment, V4 segment, and basilar artery had sufficient data for generating predicted distributions of vessel diameters. Predicted mean diameters were as follows: M1 segment, 2.55 ± 0.42 mm (95th interpercentile range [IPR]: 1.71–3.38); internal carotid artery‐cervical segment, 4.74 ± 0.64 mm (95th IPR: 3.49–5.99); internal carotid artery‐communicating segment, 3.40 ± 0.64 mm (95th IPR: 2.15–4.66); A1 segment, 1.89 ± 0.34 mm (95th IPR: 1.23–2.55); V2 segment, 3.36 ± 0.67 mm (95th IPR: 2.05–4.67); V4 segment, 2.42 ± 0.74 mm (95th IPR: 0.98–3.86); and basilar artery, 2.96 ± 0.52 mm (95th IPR: 1.94–3.97). CONCLUSION Cerebral vessel diameter measurements can vary substantially due to patient‐specific factors and imaging techniques. This literature review highlights the diverse range of vessel sizes observed in different patient populations, emphasizing the need for anatomical models that accurately represent clinical observations.

Relapsing polychondritis (clinical observations)

Relapsing polychondritis (RPC) is an autoimmune disease manifested by both repeated attacks and a persistent inflammatory process with progressive destruction of cartilaginous structures, in particular, chondritis of the ears, nose, larynx, bronchi, and joints. RPC is a rare disease (about 1000 cases have been described worldwide). Diagnosis of RPC and the choice of treatment tactics are very difficult, which is associated with the rarity of the pathology, undulating, unpredictable course, and the lack of specific laboratory markers.The clinical observations presented in the article confirm the complexity of diagnosing RPC. Before the disease was verified, both patients repeatedly consulted different specialists: the first patient was diagnosed 3 months after the onset of characteristic symptoms of RPC, and the second patient – 1.5 years later. Late diagnosis and the lack of a unified approach to treatment were the reason for the development of prognostically unfavorable lesions in the second patient – chondritis and perichondritis of the larynx.

SAFETY ASSESSMENT OF AYURVEDIC GOLD MEDICATION SUVARNA BHASMA, IN WISTAR RATS

Suvarna bhasma (SB) contains gold and lead, which are highly potent metals and are toxic in their crude form. This study evaluated the safety profile of the medication. Suvarna bhasma was administered for 90 consecutive days orally at three doses (10.23 mg kg-1, 40.92 mg kg-1 and 102.3 mg kg-1 body weight) to wistar rats. Clinical observations, feed and water consumption, and body weight changes were noted during the study period. On the 91st day, hematological, biochemical and histopathological changes were studied. There was a significant decrease in body weight of rats at a low dose (10.23 mg kg-1) at fourth week, which could not be correlated with feed and water consumption findings. Thus, change was not considered as a treatment-related effect. Suvarna bhasma showed no evident untoward effect in haematological, biochemical and histopathological parameters in the 90 day-subchronic toxicity study (OECD 408 guidelines) and was safe in Wistar rats.

Proposal of a classification of cannulation damage in vascular access grafts based on clinical, ultrasound, and microscopic observations.

Arteriovenous grafts (AVGs) serve as an alternative to native arteriovenous fistulas (AVFs) in the context of hemodialysis patient life planning. AVGs are more susceptible to developing outflow stenosis (due to intimal hyperplasia), thrombosis, and infections. However, an often overlooked contributor to AVG failure is cannulation damage. The objective of this paper is to assess the impact of cannulations on AVGs. We aim to establish a classification of AVG damage by comparing clinical data and ultrasound images with microscopic morphological findings obtained from explanted grafts. This study is conducted at a single center. We included all patients who underwent AVG creation between 2011 and 2019. Comprehensive data on clinical history, follow-up, and complications were collected and reviewed. Duplex ultrasound (DUS) characteristics were documented, and all grafts explanted during the analysis period underwent optical microscopy evaluation. Finally, clinical data, along with DUS and microscopic findings, were integrated to derive a damage classification. During the study period, 247 patients underwent 334 early cannulation AVGs. The median follow-up duration was 714 days (IQR 392, 1195). One hundred eleven (33%) grafts were explanted. Clinical data and DUS findings were utilized to formulate a four-grade classification system indicating increasing damage. Cannulation damage alone does not solely account for AVG failure. It results from a biological host-mediated process that promotes the growth of intimal hyperplasia at the cannulation sites. This process is not clinically significant within the initial 2 years after AVG creation.

A Systematic Review and Case Illustrations of Misdiagnosing Intracranial Aneurysms.

Modern neuroimaging methods do not completely rule out false diagnoses of intracranial aneurysms which can lead to an unwarranted operation associated with risks of complications.However,surgical interventions for falsely diagnosed aneurysms are quite rare. The purpose of this study is to demonstrate two clinical cases of false-positive aneurysms and a systematic review of the literature dedicated to the incidence and etiology of false-positive aneurysms, identifying risk factors associated with false-positive aneurysms. A literature search in two databases (PubMed and Web of Science) using keywords "mimicking an intracranial aneurysm", "presenting as an intracranial aneurysm", "false positive intracranial aneurysms", and "neurosurgery" was conducted. A total of 243 papers were found in the initial search in two databases. Sixteen papers (including 20 patients) were included in the final analysis. There were 10 women and 10 men. The most common location of false-positive aneurysms was the bifurcation of the middle cerebral artery (MCA). In the posterior circulation, false-positive aneurysms were identified either on the basilar artery, or at the vertebro-basilar junction. The main causes of false intracranial aneurysm diagnosis included artery occlusion with vascular stump formation, infundibular widening, fenestration, arterial dissection, contrast extravasation, and venous varix.In conclusion, summarizing the results of our analysis, we can say that surgical interventions for false-positive aneurysms are an underestimated problem in vascular neurosurgery. Despite extremely rare published clinical observations, the actual frequency of erroneous surgical interventions for false-positive aneurysms is unknown.

CNN-Based Pattern Classifiers for Precise Identification of Perinatal EEG Biomarkers of Brain Injury in Preterm Neonates

Electroencephalographic (EEG) monitoring is important for the diagnosis of hypoxic-ischemic (HI) brain injury in high-risk preterm infants. EEG monitoring is limited by the reliance on expert clinical observation. However, high-risk preterm infants often do not present observable symptoms due to their frailty. Thus, there is an urgent need to find better ways to automatically quantify changes in the EEG these high-risk babies. This article is a first step towards this goal. This innovative study demonstrates the effectiveness of deep Convolutional Neural Networks (CNN) pattern classifiers, trained on spectrally-detailed Wavelet Scalograms (WS) images derived from neonatal EEG sharp waves—a potential translational HI biomarker, at birth. The WS-CNN classifiers exhibit outstanding performance in identifying HI sharp waves within an exclusive clinical EEG recordings dataset of preterm infants immediately after birth. The work has impact as it demonstrates exceptional high accuracy of 99.34 ± 0.51% cross-validated across 13,624 EEG patterns over 48 h raw EEG at low 256 Hz clinical sampling rates. Furthermore, the WS-CNN pattern classifier is able to accurately identify the sharp-waves within the most critical first hours of birth (n = 8, 4:36 ± 1:09 h), regardless of potential morphological changes influenced by different treatments/drugs or the evolutionary ‘timing effects’ of the injury. This underscores its reliability as a tool for the identification and quantification of clinical EEG sharp-wave biomarkers at bedside.

Computational modeling reveals key factors driving treatment-free remission in chronic myeloid leukemia patients

Patients with chronic myeloid leukemia (CML) who receive tyrosine kinase inhibitors (TKIs) have been known to achieve treatment-free remission (TFR) upon discontinuing treatment. However, the underlying mechanisms of this phenomenon remain incompletely understood. This study aims to elucidate the mechanism of TFR in CML patients, focusing on the feedback interaction between leukemia stem cells and the bone marrow microenvironment. We have developed a mathematical model to explore the interplay between leukemia stem cells and the bone marrow microenvironment, allowing for the simulation of CML progression dynamics. Our proposed model reveals a dichotomous response following TKI discontinuation, with two distinct patient groups emerging: one prone to early molecular relapse and the other capable of achieving long-term TFR after treatment cessation. This finding aligns with clinical observations and underscores the essential role of feedback interaction between leukemic cells and the tumor microenvironment in sustaining TFR. Notably, we have shown that the ratio of leukemia cells in peripheral blood (PBLC) and the tumor microenvironment (TME) index can be a valuable predictive tool for identifying patients likely to achieve TFR after discontinuing treatment. This study provides fresh insights into the mechanism of TFR in CML patients and underscores the significance of microenvironmental control in achieving TFR.