Expert consensus on the systemic treatment of atopic dermatitis in special populations.

With the increasing number of options for the treatment of moderate-to-severe atopic dermatitis, clinicians need guidance on a practical approach to selecting a systemic agent for specific patient populations. We convened an expert panel consisting of 12 members to conduct a literature review and summarize relevant data related to six scenarios of clinical interest: comorbid asthma, ocular surface disease, history of cancer, past and ongoing infections of interest (including herpes simplex virus, herpes zoster, hepatitis B, and tuberculosis), pregnancy and lactation, and the elderly. We performed a literature search and examined each clinical scenario with respect to three major categories of available systemic agents: traditional systemics (azathioprine, cyclosporine A, methotrexate, and mycophenolate mofetil), Janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib), and biologics (dupilumab, lebrikizumab, and tralokinumab). The expert panel and steering committee met virtually to review the data and discuss the drafted consensus statements. A modified Delphi process was used to arrive at a set of final consensus statements related to the systemic treatment of AD in these specific patient populations. To provide practical guidance on the choice of systemic therapy for atopic dermatitis in these six topics of clinical interest, 25 expert consensus statements and a summary of the supporting data are presented herein.

In vivo monitoring of vascularization and oxygenation of tumor xenografts using optoacoustic microscopy and diffuse optical spectroscopy.

The research is devoted to comparison of the blood vessel structure and the oxygen state of three xenografts: SN-12C, HCT-116 and Colo320. Differences in the vessel formation and the level of oxygenation are revealed by optoacoustic (OA) microscopy and diffuse optical spectroscopy (DOS) respectively. The Colo320 tumor is characterized by the highest values of vessel size and fraction. DOS showed increased content of deoxyhemoglobin that led to reduction of saturation level for Colo320 as compared to other tumors. Immunohistochemical (IHC) analysis for CD31 demonstrates the higher number of vessels in Colo320. The IHC for hypoxia was consistent with DOS results and revealed higher values of the relative hypoxic fraction in Colo320.

Combined Application of Dual-Wavelength Fluorescence Monitoring and Contactless Thermometry during Photodynamic Therapy of Basal Cell Skin Cancer.

The aim of the study was to assess the capabilities of combined application of dual-wavelength fluorescence visualization and contactless skin thermometry during photodynamic therapy monitoring (PDT) of basal cell cancer. MATERIALS AND METHODS: The study was performed at the University Clinic of Privolzhsky Research Medical University (Nizhny Novgorod). Nine clinically, dermatoscopically, and histologically verified foci of basal cell skin cancer were exposed to PDT sessions (wavelength of 662 nm, light dose density of 150 J/cm2) with systemic application of chlorin-based photosensitizer Fotoditazin. A semiconductor laser system Latus-T (Russia) was employed for irradiation. Dual-wavelength fluorescence visualization and contactless thermometry with an IR pyrometer were used to monitor the PDT sessions. RESULTS: The PDT sessions of nine foci of basal cell cancer were carried out under the control of fluorescence imaging and contactless thermometry. Photosensitizer photobleaching in all foci amounted to 40% signifying a percent of photosensitizer involved in the photodynamic reaction. It has been shown that the combined employment of dual-wavelength fluorescence monitoring and contactless thermometry during the PDT of basal cell skin cancer allows oncologists to control simultaneously the degree of photosensitizer photobleaching and the depth of the photodynamic effect in tissues, the extent of involving the mechanisms associated with hyperthermia as well as the correctness of the procedure conducting. In the course of 9-month dynamic follow-up after the treatment, no clinical and dermatoscopic signs of recurrence were found. CONCLUSION: A bimodal control of PDT enables the assessment of the correctness and efficacy of the procedure performance. The contactless control of tissue heating allows ensuring the temperature mode for hyperthermia realization, while the fluorescence monitoring makes it possible to evaluate the accumulation of the photosensitizer in the tumor and the depth of the PDT action as well as to predict the procedure efficacy based on the photobleaching data. The complementary use of these techniques allows the adjustment of the mode directly in the course of the PDT procedure. The acquisition of the sufficient statistical data on the combined monitoring will result in the development of a novel PDT protocol.

Diffuse optical spectroscopy assessment of rodent tumor model oxygen state after single-dose irradiation.

Modern radiation therapy of malignant tumors requires careful selection of conditions that can improve the effectiveness of the treatment. The study of the dynamics and mechanisms of tumor reoxygenation after radiation therapy makes it possible to select the regimens for optimizing the ongoing treatment. Diffuse optical spectroscopy (DOS) is among the methods used for non-invasive assessment of tissue oxygenation. In this work DOS was used forin vivoregistration of changes in oxygenation level of an experimental rat tumor after single-dose irradiation at a dose of 10 Gy and investigation of their possible mechanisms. It was demonstrated that in 24 h after treatment, tumor oxygenation increases, which is mainly due to an increase in the oxygen supply to the tissues. DOS is demonstrated to be efficient for study of changes in blood flow parameters when monitoring tumor response to therapy.

[Noninvasive estimation of the oxygen state of experimental tumor by diffuse optical spectroscopy].

The potentialities of diffuse optical spectroscopy for the noninvasive estimation of the oxygen state of experimental tumors have been demonstrated. The distribution of total, oxygenated and deoxygenated hemoglobin, as well as the level oxygen saturation of blood have been shown using two tumor models differing in the histological structure and functional characteristics. The results obtained by the optical method have been verified by immunohistochemical examination of tissue specimens with the exogenous hypoxia marker pimonidazole.

[Differences in the functional activity of human neutrophilic granulocytes in their interactions with semiconductor quantum dots].

The uptake of quantum dots (QD-5 nm particles of CdSe/ZnS-mercaptoacetic acid) by human neutrophilic granulocytes was studied using the methods of scanning laser and scanning probe microscopy. The results show that the neutrophilic granulocytes may be subdivided into three subpopulations: (1) the cells with no uptake of QD (10.0 +/- 2.0%); (2) cells that accumulate QD in their volume (28.0 +/- 1.9%), and (3) cells, surrounded by a halo of QD (59.0 +/- 2.2%). The dispersion of these characteristics may suggest the differences in neutrophilic granulocyte plasma membrane permeability.

Complementary use of cross-polarization and standard OCT for differential diagnosis of pathological tissues.

An experimental standard optical coherence tomography (OCT) setup that can be easily modified for cross-polarization OCT (CP OCT) operation has been developed to perform differential diagnosis of pathological tissues. The complementary use of CP OCT, a technique that provides a map of cross-polarization backscattering properties of an object being studied by means of low-coherence interferometry, and standard OCT imaging improves the specificity of diagnostics of pathological changes occurring in tissues. It is shown that healthy, neoplastic and scar tissues of the esophagus have different cross-polarization backscattering properties. A comparative analysis of CP OCT, OCT and histological images from one and the same tissue area has been made. A close correlation between the location of collagen fibers in biological tissue and signal intensity in CP OCT images is found.

[Transplantation of organic culture of adrenal grand cortical substance in the treatment of post-adrenalectomy hypocorticoidism]. / Transplantatsiia organnoi kul'tury korkovogo veshchestva nadpochechnikov v lechenii postadrenaléktomicheskogo gipokortitsizma.

The organ culture transplantation of the adrenals cortical substance of a newborn piglets was applied while 94 patients treatment to whom total adrenalectomy for Itsenko--Cushing disease was done. Significant lowering of the substitutional hormonal therapy (steroid preparations) dosage was permitted due to the noted improvement of hypocorticism clinical course and an organism hormonal security indexes. The clinical effect duration is 6-9 months. The methods physiologically substantiated, technically simple, economically advantageous, do not cause the side effects.

[Auto- and xenotransplantation of testicular organ culture to castrated rats and rats with experimental hypogonadism]. / Auto- i ksenotransplantatsiia organnykh kultur simíannykiv kastrovanym shchuram ta shchyram iz eksperymentalnym hipohonadizmom.

The organ culture from the testes of newborn pigs able to produce the basic androgens such as testosterone, dehydroepiandrosterone, androstenedione and androstenediol has been obtained. CdCl2 administration to the rats in a dose of 0.055 mg/100 g of body weight and gonadectomy resulted in the development of two experimental models of hypogonadism. Autotransplantation of organ culture from the rat testes and xenotransplantation of the testes from newborn pigs to the rats with experimental hypogonadism provoked an increase in blood plasma testosterone for 1.5 and 3 months, respectively. Organ cultures from the testes of newborn pigs can be recommended for clinical purposes.

[The transplantation of beta-cell cultures in the treatment of insulin-dependent diabetes mellitus in children]. / Transplantatsiia kul'tur beta-kletok v lechenii insulinzavisimogo sakharnogo diabeta u detei.

Over 100 transplantations were performed in 86 children and adolescents with a severe course of insulin dependent diabetes mellitus. A good effect was achieved in 81 +/- 6%, in other cases the effect was uncertain. Therapy resulted in a significantly higher rate of cases of stable compensation with a lesser number of injections and a stable dose of insulin, in stabilization and regression of some complications. Transplantation was followed by an increase in the level of C-peptide 3-4 times as compared to the basal one for a period of 6 mos. A better effect was noted in a group of patients with a high residual secretion of C-peptide. An assumption was made of simultaneous secretory activity of a graft and residual beta-cell-stimulated endogenous production of insulin.

[The cytological and hormonal characteristics of cell cultures from the testes of newborn piglets]. / Tsitologicheskaia i gormonal'naia kharakteristika kletochnykh kul'tur iz semennikov novorozhdennykh porosiat.

A cell culture of neonatal pig testes has been studied. Leydig cells, Sertoli cells, sex cells and fibroblasts have been identified by cytologic and cytochemical research methods, Gonadotropin concentration (0.1 U/ml) of nutritional medium, increases proliferation of the Leydig cells and increases their 3-beta-ol-steroiddehydrogenase activity as well as increases amount of lipid inclusions and stimulates testosterone production. The cell culture can be used to treat some forms of hypogonadism.

[The histochemical detection of insulin in a culture of pancreatic endocrine tissue by using the pseudoisocyanine and immunofluorescence methods]. / Gistokhimicheskoe vyiavlenie insulina v kul'ture éndokrinnoi tkani podzheludochnoi zhelezy s pomoshch'iu psevdoizotsianinovogo i immunofliuorestsentnogo metodov.

Histochemical pseudoisocyanin and immunofluorescent methods were employed to investigate the level of insulin in cultivated pancreatic islet tissue (PIT) using two techniques: 1) staining of isolated PIT, cultivated on mica sheets; 2) staining of cultivated PIT sections. Stained sections ensure better results of microscopic and photometric investigations. On the whole, the most optimum method for histochemical analysis of the state of cultivated PIT is the combination of the above two techniques.

[Experience in xenografts of pancreatic islet cell cultures after surgical treatment of chronic pancreatitis]. / Opyt ksenotransplantatsii kul'tur kletok pankreaticheskikh ostrovkov posle khirurgicheskogo lecheniia khronicheskogo pankreatita.

Xenotransplantation of the pancreatic islet cells was performed in 8 patients with chronic pancreatitis and concomitant diabetes mellitus, operated on the pancreas. In 2 patients, the rejection of the cells transplanted occurred. The causes of failure and possibilities for improving the technique are analysed.

[Effect of the transplantation of cultured pancreatic islet cell on the status of diabetic microangiopathy]. / Vliianie transplantatsii kul'tury ostrovkovykh kletok podzheludochnoi zhelezy na sostoianie diabeticheskikh mikroangiopatii.

Investigation of the effect of allo- and xenotransplantation of pancreatic tissue cultures on the hemodynamic indices of 85 patients with diabetes mellitus using ophthalmoscopy, biomicroophthalmoscopy, integral rheography, capillaroscopy and clinical biochemical tests at varying time (from 3 mos to 4 yrs.) showed a gradual improvement of the ophthalmological picture of the fundus of the eye in 58 patients (86%) during the first 9 mos with further stabilization of a process. Lower limb improvement was noted in 18% of the patients, stabilization of a process--in 74%. The improvement of the renal clinico-biochemical indices was noted in 47-67%. Contraindications for beta = culture transplantation were diabetic glomerulosclerosis with stage III chronic renal insufficiency and retinopathy of diabetorenal type.

[Ultrastructural characterization of organ cultures of adrenal glands of newborn pigs]. / Ul'trastrukturnaia kharakteristika organnykh kul'tur nadpochechnikov novorozhdennykh porosiat.

Electron microscopic investigation of newborn pig adrenal organ cultures performed for determination of optimum time for xenotransplantation, has shown that the most viable and functional adrenocorticocytes preserving signs of zonal specificity are revealed on the 5th day of cultivation. Later on (the 15th-30th day) morphological changes indicate increasing dedifferentiation of most secretory cells, the capacity to corticosteroidogenesis (judging by the state of steroid-synthesizing organelles) in some adrenocorticocytes being preserved up to 25-30 days. Thus, the most suitable time for xenotransplantation of adrenal organ cultures is the 5th day.

[Effect of a number of cryoprotective agents on the structure and function of cultured pancreatic islet cells of newborn piglets]. / Izuchenie vliianiia riada krioprotektorov na strukturu i funktsiiu kul'tur ostrovkovykh kletok podzheludochnoi zhelezy novorozhdennykh porosiat.

The paper is concerned with the results of a direct effect of widely used cryoprotectors on the structure and function of cell culture in pancreatic islet cells. It has been concluded that PEO-400 (polyethylene oxide) concentration up to 10% and DMSO (dimethyl silfoxide) concentration up to 7.5% do not influence the toxic effect of morphofunctional features of pancreatic cells.

[Morphofunctional changes in a culture of pancreatic islet cells from newborn piglets as affected by Coxsackie B3 viruses]. / Morfofunktsional'nye izmeneniia v kul'ture ostrovkovykh kletok podzheludochnoi zhelezy novorozhdennykh porosiat pod vliianiem virusov Koksaki B3.

The direct influence of Coxsackie virus B-3 and its selected variants Abent+ and Abent- on the function and structure of neonatal pig pancreatic islet cells in monolayer cultures was studied. The viruses under study possessed cytopathogenic activity and were capable of reproduction. The Abent- variant of Coxsackie virus B-3 possessed the most pronounced cytopathogenic activity. Direct correlation between virus reproduction and insulin concentration in a culture medium was established.