Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN.

BACKGROUND: In the phase III CASPIAN study, first-line durvalumab in combination with etoposide plus either cisplatin or carboplatin (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small-cell lung cancer (ES-SCLC). Durvalumab plus tremelimumab plus EP numerically improved OS versus EP, but did not reach statistical significance. Here we report updated OS in censored patients after median follow-up of >3 years. PATIENTS AND METHODS: 805 patients with treatment-naïve ES-SCLC were randomized 1 : 1 : 1 to durvalumab plus EP, durvalumab plus tremelimumab plus EP, or EP. The two primary endpoints were OS for durvalumab plus EP versus EP and for durvalumab plus tremelimumab plus EP versus EP. RESULTS: As of 22 March 2021 (median follow-up 39.4 months, 86% maturity), durvalumab plus EP continued to demonstrate improved OS versus EP: hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.60-0.86; nominal P = 0.0003]; median OS was 12.9 versus 10.5 months, and 36-month OS rate was 17.6% versus 5.8%. Durvalumab plus tremelimumab plus EP continued to numerically improve OS versus EP: HR 0.81 (95% CI: 0.67-0.97; nominal P = 0.0200); median OS was 10.4 months, and 36-month OS rate was 15.3%. Twenty-seven and nineteen patients in the durvalumab plus EP and durvalumab plus tremelimumab plus EP arms, respectively, remained on durvalumab treatment at data cut-off. CONCLUSIONS: Three times more patients were estimated to be alive at 3 years when treated with durvalumab plus EP versus EP, with the majority still receiving durvalumab at data cut-off, further establishing durvalumab plus EP as first-line standard of care for ES-SCLC.

Application of W-band 19F electron nuclear double resonance (ENDOR) spectroscopy to distance measurement using a trityl spin probe and a fluorine label.

Recently, Marina Bennati and coworkers (M. Bennati et al., Angew. Chem., Int. Ed., 2020, 59, 373-379., M. Bennati et al., J. Magn. Reson., 2021, 333, 107091) proposed to use electron nuclear double resonance (ENDOR) spectroscopy in the W-band for a pair of labels, nitroxide and 19F, for measurements of short (0.5-1.0 nm) distances in biomolecules. In our paper, we investigated the suitability of high-field ENDOR spectroscopy in the W-band for pairs of triarylmethyl and fluorine labels using five newly synthesized model compounds. It is shown that the application of strong magnetic fields allows distinguishing nuclear frequencies of 19F and protons with sufficient resolution. On the one hand, in contrast to nitroxides, for triarylmethyl radicals, it is not necessary to obtain spectra in different orientations owing to low g-factor anisotropic and long electron spin relaxation times of triarylmethyls. On the other hand, the size of the triarylmethyl radical is substantially larger than that of nitroxide and comparable with measured distances. We theoretically analyzed the suitability of the dipole-dipole approach for triarylmethyl to be used in a 19F ENDOR experiment and determined limitations of this approach. Finally, for comparison, we performed paramagnetic relaxation enhancement (PRE) NMR on the same compounds. In addition, we applied this approach to study the process of a thiol exchange between molecules of triarylmethyl-labeled and 19F-labeled human serum albumin (HSA).

[The state of regional lymph nodes in chronic tonsillitis according to ultrasound]. / Sostoyanie regionarnykh limfaticheskikh uzlov pri khronicheskom tonzillite po dannym ul'trazvukovogo issledovaniya.

Despite the variety of chronic tonsillitis clinical symptoms, none of the known signs of this disease is typical for it. PURPOSE OF STUDY: Is development of a method for differential diagnosis of complicated (toxic-allergic) and uncomplicated (simple) forms of chronic tonsillitis. METHODS: 147 patients were divided into 2 groups: 1) 61 (42%) - with a simple form and 2) 86 (58%) - with a toxic-allergic form of chronic tonsillitis of the II degree. Patients underwent ultrasound examination of regional lymph nodes, to determine their localization, quantity (single, multiple), shape, size and structure. RESULTS: According to ultrasound data, it was revealed that for the simple form of chronic tonsillitis the following characteristics of the lymph nodes were typical - bean-like form, single, clear contours, homogeneous central parts and reduced vascularization; for the toxic-allergic form of chronic tonsillitis, the following characteristics of lymph nodes were revealed - oval shape, lymph nodes conglomerates, hypoechoic central parts, increased vascularization and irregular shape of the gates. CONCLUSION: The proposed method allows to quickly and efficiently conduct differential diagnosis of chronic tonsillitis. This technique is easily reproducible in the conditions of any (outpatient, inpatient) medical facility using standard equipment for ultrasound examination, does not require the use of any drugs.

Interfacial tensiometry and dilational surface visco-elasticity of biological liquids in medicine.

Dynamic surface tensions and dilational visco-elasticity are easy accessible parameters of liquids. For human body liquids, such as urine, blood serum, amniotic fluid, gastric juice, saliva and others, these parameters are very characteristic for the health status of people. In case of a disease the composition of certain liquids specifically changes and the measured characteristics of dynamic surface tension of the dilational surface elasticity and viscosity reflect these changes in a clear way. Thus, this kind of physico-chemical measurements represent sensitive tools for evaluating the severity of a disease and can serve as control tool for the efficiency of applied therapies. The overview summarises the results of a successful work over about 25years on this subject and gives specific insight into a number of diseases for which the diagnostics as well as the therapy control have been significantly improved by the application of physico-chemical experimental techniques.

Hyperfine interactions of narrow-line trityl radical with solvent molecules.

The electron nuclear dipolar interactions responsible for some dynamic nuclear polarization (DNP) mechanisms also are responsible for the presence formally in CW EPR spectra of forbidden satellite lines in which both the electron spin and a nuclear spin flip. Such lines arising from (1)H nuclei are easily resolved in CW EPR measurements of trityl radicals, a popular family of DNP reagents. The satellite lines overlap some of the hyperfine features from (13)C in natural abundance in the trityl radical, but their intensity can be easily determined by simple simulations of the EPR spectra using the hyperfine parameters of the trityl radical. Isotopic substitution of (2)H for (1)H among the hydrogens of the trityl radical and/or the solvent allows the dipolar interactions from the (1)H on the trityl radical and from the solvent to be determined. The intensity of the dipolar interactions, integrated over all the (1)H in the system, is characterized by the traditional parameter called reff. For the so-called Finland trityl in methanol, the reff values indicate that collectively the (1)H in the unlabeled solvent have a stronger integrated dipolar interaction with the unpaired electron spin of the Finland trityl than do the (1)H in the radical and consequently will be a more important DNP route. Although reff has the dimensions of distance, it does not correspond to any simple physical dimension in the trityl radical because the details of the unpaired electron spin distribution and the hydrogen distribution are important in the case of trityls.

Dynamic surface tension and surface rheology of biological liquids.

The paper presents results of dynamic and equilibrium surface tension measurements (using a maximum bubble pressure instrument) of serum and urine samples that were obtained from 80 healthy human of various sexes and ages. These data were compared with surface tension measurements of biological liquids obtained from patients suffering from malignant neoplasm of corpus uteri (n=5) and cervix uteri (n=31). In addition, surface dilatational rheology was determined on 32 samples using a drop shape method. The dilatational rheology data were compared with the dynamic surface tension data. Although some trends were found, no significant correlations exist between surface tension and rheology data and any of the disease states or stages. It is difficult to explain these findings in the framework of known mechanisms. However, our studies demonstrate that dynamic interface tensiometry of human biological liquids provide new insight into the biophysical behavior of these liquids, most likely reflecting compositional changes of them during ageing, the course of cancer and as a consequence of therapeutical interventions.

Studies on the application of dynamic surface tensiometry of serum and cerebrospinal liquid for diagnostics and monitoring of treatment in patients who have rheumatic, neurological or oncological diseases.

Human biological liquids comprise various surfactants, which adsorb at liquid interfaces and lead to a variation in surface tension. The adsorption processes involving low molecular weight surfactants, proteins and phospholipids play a vital role in the physiological functions of the human organism, especially if large surfaces are involved (e.g., gas exchange in lungs, metabolism of kidneys, liver and brain). Dynamic surface tensiometric studies of biological liquids like serum and cerebrospinal fluid provide surrogate parameters that reflect surface tension phenomena. We provide dynamic surface tension data of serum and cerebrospinal fluid that were collected from healthy volunteers and patients with rheumatic, neurological or oncological diseases. Our studies indicate that dynamic surface tension data are helpful for diagnostic purposes and for monitoring of therapeutic interventions.

[Dynamic middle-phase tensiometry of blood and urine in female patients with malignant tumors of the reproductive organs]. / Dinamicheskaia mezhfaznaia tenziometriia krovi i mochi pri zlokachestvennykh opukholiakh reproduktivnykh organov zhenshchin.

An improved version of the MPT2 (LAUDA) computerized tensiometer (Germany) was used to measure dynamic surface tension (ST) of blood and urine by the maximum bubble pressure method in patients with tumors of the uterus, vagina and cervical canal. Relatively low blood and urine ST values at t-->infinity and serum at t = 1 s were registered. Combined radiotherapy involved oppositely-directed changes in the equilibrium (static) ST of the biological fluids as well as a urine ST inhibition in the surface short-life range (t = 0.01 s). The slope of blood serumtension curves by the end of treatment was close to that in healthy females.

[Dynamic interphase tensiometry of the cerebrospinal fluid and blood serum in nervous system tumors]. / Dinamicheskaia mezhfaznaia tenziometriia spinnomozgovoi zhidkosti i syvorotki krovi pri opukholiakh nervnoi sistemy.

Dynamic superficial tension (ST) of spinal fluid (SF) and blood serum in patients with CNS tumors was investigated. The maximum bubble tension was measured by a MPT2 computer tensiometer (LAUDA). There were decreases in ST of blood serum at t = 1 and t-->infinity, increases in ST at t = 0.01 and decreases in the angle on SF tensiograms. The parameters of interphasic tensiometry of the biological fluids depend on content of biologically active substances severity of the neurological symptomatology and duration of disease. Successive surgical treatment is followed by normalization of SF and blood serum ST.

[The dynamic surface tension of the blood and urine in chronic glomerulonephritis]. / Dinamicheskoe poverkhnostnoe natiazhenie krovi i mochi pri khronicheskom glomerulonefrite.

Dynamic surface-tension (S-T) was investigated of blood and urine of healthy individuals and patients with chronic glomerulonephritis by the proposed method of maximum pressure in a bubble with the aid of the computer-assisted device tensometer MPT-1 (Lauda, Germany). Patterns of changes in dynamic and static S-T were found out as were those of the slope of the curve in patients with mesangioproliferative and mesangiocapillary variants of the condition, in nephrotic syndrome and chronic renal insufficiency. Correlation type comparison was performed of physical-and-chemical properties of biological fluids to parameters characterizing protein and fat exchange. Relationship between dynamic S-T and biochemical composition of blood and urine was revealed. Diagnostic value of results of the studies made is discussed.