Tailoring postoperative management through sentinel lymph node biopsy in low- and intermediate-risk endometrial cancer - the SENTRY clinical trial.

BACKGROUND: While total hysterectomy and bilateral salpingo-oophorectomy without lymph node staging are standard for low- and intermediate-risk endometrial cancer, certain histopathologic factors revealed after surgery can necessitate additional interventions. Our study assessed the influence of sentinel lymph node biopsy on postoperative decision-making. MATERIALS AND METHODS: In the SENTRY trial (July 2021 - February 2023), we enrolled patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IA-IB low-grade endometrioid endometrial cancer. Laparoscopic sentinel lymph node mapping using indocyanine green was performed alongside total hysterectomy with bilateral salpingo-oophorectomy. Subsequent management changes based on sentinel lymph node biopsy results were evaluated. The trial was registered at ClinicalTrials.gov (NCT04972682). RESULTS: Of the 100 enrolled participants, a bilateral detection rate of 91% was observed with a median detection time of 10 min (interquartile range 8-13 min). Sentinel lymph node metastases were found in 8% (N = 8) of participants. Postoperative FIGO staging increased in 15% (N = 15) and decreased in 5% (N = 5) of patients. Sentinel lymph node biopsy results altered the adjuvant treatment plan for 20% (N = 20): external beam radiotherapy was omitted in 12% (N = 12) while 6% (N = 6) had external beam radiotherapy +/- systemic chemotherapy added due to sentinel lymph node metastases. In 2% (N = 2), the external beam radiotherapy field was expanded with the paraaortic region. No intraoperative complications were reported and no 30-day major morbidity and mortality occurred. Throughout a median follow-up of 14 (95% CI 12-15 months, neither patient-reported lymphedema nor pelvic recurrence surfaced in the cohort. CONCLUSIONS: Sentinel lymph node biopsy using indocyanine green is a safe procedure and allows tailoring adjuvant therapy in presumed low- and intermediate-risk endometrial cancer. It assists in avoiding external beam radiotherapy overtreatment and introducing additional modalities when necessary.

A single psychotomimetic dose of ketamine decreases thalamocortical spindles and delta oscillations in the sedated rat.

BACKGROUND: In patients with psychotic disorders, sleep spindles are reduced, supporting the hypothesis that the thalamus and glutamate receptors play a crucial etio-pathophysiological role, whose underlying mechanisms remain unknown. We hypothesized that a reduced function of NMDA receptors is involved in the spindle deficit observed in schizophrenia. METHODS: An electrophysiological multisite cell-to-network exploration was used to investigate, in pentobarbital-sedated rats, the effects of a single psychotomimetic dose of the NMDA glutamate receptor antagonist ketamine in the sensorimotor and associative/cognitive thalamocortical (TC) systems. RESULTS: Under the control condition, spontaneously-occurring spindles (intra-frequency: 10-16 waves/s) and delta-frequency (1-4 Hz) oscillations were recorded in the frontoparietal cortical EEG, in thalamic extracellular recordings, in dual juxtacellularly recorded GABAergic thalamic reticular nucleus (TRN) and glutamatergic TC neurons, and in intracellularly recorded TC neurons. The TRN cells rhythmically exhibited robust high-frequency bursts of action potentials (7 to 15 APs at 200-700 Hz). A single administration of low-dose ketamine fleetingly reduced TC spindles and delta oscillations, amplified ongoing gamma-(30-80 Hz) and higher-frequency oscillations, and switched the firing pattern of both TC and TRN neurons from a burst mode to a single AP mode. Furthermore, ketamine strengthened the gamma-frequency band TRN-TC connectivity. The antipsychotic clozapine consistently prevented the ketamine effects on spindles, delta- and gamma-/higher-frequency TC oscillations. CONCLUSION: The present findings support the hypothesis that NMDA receptor hypofunction is involved in the reduction in sleep spindles and delta oscillations. The ketamine-induced swift conversion of ongoing TC-TRN activities may have involved at least both the ascending reticular activating system and the corticothalamic pathway.

[Alternating hemiplegia]. / Al'terniruyushchaya gemiplegiya.

Alternating hemiplegia, a rare neurological disease that manifests in children under the age of 18 months, is characterized by transient episodes of hemiparesis of an alternating nature in the waking period. In addition to transient hemiparesis, neurological symptoms in the form of choreoathetosis, ataxia, dystonia, autonomic dysfunction, ocular apraxia, nystagmus, seizures, dysarthria and intellectual disorders may develop. Mutation in the ATP1A3 gene is the cause of the disease in more than 75% of patients. In some cases, the use of flunarizine, adenosine triphosphate and a ketogenic diet can reduce the frequency and duration of hemiplegic attacks. The authors report a case of a patient with alternating hemiplegia caused by a heterozygous mutation in exon 8 of the ATP1A3 gene (chr19: 42489098A>T, rs606231428), resulting in an amino acid substitution at position 335 (p.Val335Asp, NM_001256214.1). The use of flunarizin in a dose of 5 mg/day significantly reduces the number and duration of seizures, while oral adenosine-5-triphosphoric acid in a dose of 20 mg/kg/day is not effective.

Multi-parametric evaluation of the white matter maturation.

In vivo evaluation of the brain white matter maturation is still a challenging task with no existing gold standards. In this article we propose an original approach to evaluate the early maturation of the white matter bundles, which is based on comparison of infant and adult groups using the Mahalanobis distance computed from four complementary MRI parameters: quantitative qT1 and qT2 relaxation times, longitudinal λ║ and transverse λ⊥ diffusivities from diffusion tensor imaging. Such multi-parametric approach is expected to better describe maturational asynchrony than conventional univariate approaches because it takes into account complementary dependencies of the parameters on different maturational processes, notably the decrease in water content and the myelination. Our approach was tested on 17 healthy infants (aged 3- to 21-week old) for 18 different bundles. It finely confirmed maturational asynchrony across the bundles: the spino-thalamic tract, the optic radiations, the cortico-spinal tract and the fornix have the most advanced maturation, while the superior longitudinal and arcuate fasciculi, the anterior limb of the internal capsule and the external capsule have the most delayed maturation. Furthermore, this approach was more reliable than univariate approaches as it revealed more maturational relationships between the bundles and did not violate a priori assumptions on the temporal order of the bundle maturation. Mahalanobis distances decreased exponentially with age in all bundles, with the only difference between them explained by different onsets of maturation. Estimation of these relative delays confirmed that the most dramatic changes occur during the first post-natal year.

The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants.

Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the baby's brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio.

[A clinical test for diagnosis of myasthenic ptosis].

A clinical test for diagnosis of ptosis in myasthenia is described. We studied the effect of antiorthostatic posture with head-down position on the degree of ptosis in myasthenia, ocular myopathy of von Graefe, lesions of the oculomotor nerve and pseudoptosis. The antiorthostatic posture significantly (p<0,05) decreased the degree of ptosis only in patients with myasthenia The degree of ptosis remained unchanged in myopathy of von Graefe, lesions of the oculomotor nerve and pseudoptosis.

[Diffusion-tensor magnetic resonance tomography and tractography in multiple sclerosis: a review].

Multiple sclerosis is the most common chronic progressive inflammatory demyelinating disease of the central nervous system characterized by different clinical phenotypes, degrees of central nervous system damage and disease progression. Conventional magnetic resonance imaging has become a useful tool for diagnosis, differential diagnosis and monitoring disease progression. Recent innovations in magnetic resonance imaging give an opportunity to specify certain aspects of multiple sclerosis pathogenesis. This article is a review of diffusion-tensor magnetic resonance tomography and tractography usage in the brain and spinal cord of patients with different clinical phenotypes of multiple sclerosis. Main features of pathologically damaged white and grey matter observed using diffusion-tensor magnetic resonance tomography and tractography, correlations between different diffusion indices and disability are described. The problems of pathogenesis are discussed.

[The strategy of a parasite is to preserve and continue its species; some trends for achieving the goal].

The authors show that the strategy of parasites, which is to preserve and continue its species is accomplished mainly by providing of a trophic substrate. Opisthorichiasis is used as an example to show that the nutriceutic biomass of cholangiocytes may be increased due to gene mutations, induced proliferation of liver stem cells, their differentiation to committed ones and cholangiocellular differon elements; moreover, the proliferative processes of mesenchymal components become active in other organs of a host. During their ontogenesis in the intermediate and final hosts, the parasites work out the mechanisms for prolonging their life span to complete a full development cycle (Margaritifera margaritifera glochidia); however, predominantly the parasite-host symbiosis is attended by the latter's lameness. Predation is one of the types of symbiotic relations.

[Intraoperative monitoring of cerebral blood-flow and condition of cerebral at open and endovascular interventions in carotid system].

The aim of our research is to study hemodynamic and embolic situation during the carotid endarterectomy (CEA), carotid angioplastic and stenting (CAS), and to reveal the prognostic significance of the data provided by intraoperative monitoring of the brain blood flow in exposing acute ischemic lesions in brain. Intraoperative monitoring of blood flow in artery ophthalmic vas carried out with 60% of patients, in the middle cerebral artery-with 40% during the main stages of CEA, and with 64 patients in the middle cerebral artery during CAS. The comparison of the data of intraoperative monitoring of blood flow in middle cerebral artery with the result of brain diffusion-weighted magnetic resonance imaging (DW-MRI) 24 hours after the operation shows, that solid microembolic signals and vasospasm are prognostic signals (sensibility and specifics make up 95%) in the development of acute ischemic cerebral lesions. The monitoring of blood flow in artery ophthalmic is of the greatest diagnostic value in estimation of the hemodynamic situation, but it is of the lowest practical value in detecting microembolic signals. According to the data of the intraoperative blood flow monitoring in middle cerebral artery in group CEA the development of acute ischemic cerebral lesions were predicted with 11,1% of patients and the cause of postoperative stroke, developed by 2,9% of the patients, was specified. According to the result of DW-MRI, acute ischemic cerebral lesions were diagnosed with 21% of patients, that is, 18% of ischemic cerebral lesions were asymptomatic. In group CAS ischemic cerebral lesions were prognosed with 30% of patients, actually they were later detected with 40,6% of cases by means of DW-MRI. According to the data of intraoperative of blood flow monitoring the cause of the development of postoperative stroke was specified in 6,2% of cause; in 34,4% of cause the acute ischemic cerebral lesions were asymptomatic.

[Complicated forms of superinvasion opisthorchiasis: pathogenetic aspects].

Superinvasion opisthorchiasis is characterized by host growth retardation and weight reduction, which are due to the cleptoeffect of Opisthorchis felineus; metabolic disturbances, proliferative processes, accelerated collagen biosynthesis and biodegradation in the organs reflect parasite-host interactions as components of the system. The productive reactions of visceral pathology are initiated by the parasite's metabolites located in the liver, lung, heart, and testes.

[Morphogenesis of the structural changes of the internal organs in superinvasive opisthorchiasis].

The study of the model of superinvasive opisthorchiasis (SO) in Syrian hamsters and autopsy material obtained from patients with SO, it was shown that during the early period of pulmonary disease, the lungs underwent changes developing on the basis of delayed-type hypersensitivity reactions. In the chronic phase of SO, exudative and predominant productive reactions were revealed leading to the interstitial lung disease, fibrosing alveolitis. In the heart in SO, eosinophilic cell myocarditis was found with subsequent diffuse cardiosclerosis. In the testes, sclerotic processes with atrophy of glandulocytes (Leydig cells) and sustentocytes (Sertoli cells) were detected. The structural changes in the lungs, heart and testes were induced by parasite metabolites, that are deposited in tissues in the form of granules and conglomerates.

[Cytomorphological features of the neocortex in rats with genetic predisposition to absence epilepsy].

The aim of the study was to examine putative microstructural changes in the neocortex which accompany absence epilepsy. Rat strains WAG/Rij as a genetic model of absence epilepsy and ACI (control) were examined. Brain slices were stained after Nissl; neuronal and glial cells were identified and counted in the somatosensory, motor, and cingular cortices (in layers II/III, V, and VI, individually). In WAG/Rij rats, the density of neurons in the superficial layers (II/III) of the motor cortex appeared to be lower than in healthy control rats, whereas the density ofglial cells in WAG/Rij rats was higher. In the deep layers of the somatosensory and cingular areas, the density ofglial cells in WAG/Rijrats rats was lower as compared to control rats. The results demonstrate that absence epilepsy is associated with cytomorphological changes in the neocortex.

[A new case of trisomy in cattle]. / Novyi sluchai trisomii u krupnogo rogatogo skota.

The new type of trisomy (2n = 61, XX, +19) was found in the heifer with prognathia inferior syndrome. Correlations between trisomy of different types and phenotypic abnormalities are discussed.

[Mechanisms of early light and dark adaptation]. / Izuchenie mekhanizmov rannei svetovoi i temnovoi adaptatsii.

A possible role of transient and sustained mechanisms of vision in early light and dark adaptation was studied using the adaptive fields with different rates of luminance changes. The curve forms of early light and dark adaptation and time integration at different rates of switching on and off the adaptive field were studied as well as the changes of contrast sensitivity related to rates of background luminance changes. The data obtained confirm participation of transient and sustained mechanisms of vision in early light and dark adaptation. The contribution of each mechanism depends on the rate and direction of the luminance changes.