[The first russian experience of use of siponimod in real clinical practice]. / Pervyi rossiiskii opyt primeneniya siponimoda v real'noi klinicheskoi praktike.

Despite significant success in the treatment of multiple sclerosis achieved in the recent years, the issues of therapy for progressive forms of the disease are far from being resolved. The first medication with proven efficiency at SPMS is the oral selective sphingosine 1 phosphate (S1P) receptor modulator siponimod. Before the registration of siponimod in Russia, Novartis company organized a «Managed access program to enable siponimod in patients with secondary progressive multiple sclerosis without satisfactory alternative therapy¼. For the period from September 2020 to May 2021, 10 patients with SPMS with exacerbations were included in the programme by RAS. The results of the treatment of the patients under the programme were similar to the results of previously controlled studies. The medication was well tolerated and the expected side effects (mainly lymphopenia and Elevated transaminases) were not more severe than moderate and were stopped by temporary cancel of the current treatment or concomitant therapy. During 1 year of therapy, the stabilization of condition of all patients and positive dynamics was noticed, including a decrease in the EDSS score in 44% of patients. Despite the limited number of patients and time of observation, the safety and efficacy of siponimod in patients with SPMS are quite high. The use of the medication in routine clinical practice does not require extraordinary methods of observation and control, but nevertheless includes genetic examination before the prescription of therapy, regular monitoring of clinical blood and biochemical parameters.

SNCA variants and alpha-synuclein level in CD45+ blood cells in Parkinson's disease.

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. Impaired metabolism of alpha-synuclein (SNCA) and its aggregation are implicated in PD pathogenesis. SNCA has been identified as a highly significant genetic risk loci associated with the sporadic form of PD in across populations in GWAS and replicative studies. In this study we conducted a genetic analysis of five SNCA single nucleotide polymorphisms (SNPs) (rs356219, rs2619364, rs11931074, rs2583988, rs356168) in 458 PD patients and 353 from North-West region of Russia. We also assessed an association of studied SNPs with alpha-synuclein levels in homogeneous cell fraction of CD45+ blood cells in PD patients and controls. An association with PD was shown for SNPs rs356219, rs11931074, rs356168. After correction for covariates the significant association with the disease only for rs11931074 and rs356168 was shown. Alpha-synuclein level in peripheral blood CD45+ cells was significantly increased in PD patients compared to control subjects (р = 0.02). The effect of SNCA rs356219 and rs356168 on CD45+ alpha-synuclein level in PD patients and control groups was shown. At the same tame the increase of CD45+ alpha-synuclein level in PD patients was revealed only in risk allele carriers as for rs356219 and rs356168 SNPs. Therefore, our study was the first that demonstrated the increased level of alpha-synuclein in CD45+ blood cells in PD patients and showed that it could be influenced by SNCA rs356168 and rs356219. In conclusion we confirmed the significance of the SNCA locus in the PD development.

[Neuroprotection therapy of multiple sclerosis with high doses of ethylmethylhydroxypyridine succinate]. / Vozmozhnosti neiroprotektsii pri rasseyannom skleroze: opyt primeneniya vysokikh doz preparata etilmetilgidroksipiridina suktsinat.

AIM: To study the therapeutic action of ethylmethylhydroxypyridine succinate (mexidol) on the neurodegeneration in multiple sclerosis (MS). MATERIAL AND METHODS: Fifty-two MS patients and 24 healthy controls were examined using DTI MRI with tractography. RESULTS AND CONCLUSION: Ethylmethylhydroxypyridine succinate can prevent the progression of neurodegenerative processes in MS. However, further clinical trials are needed to confirm the results obtained in this study.

[Regional metabolic changes of supraventricular tissue in patients with relapsing-remitting and secondary-progressive multiple sclerosis]. / Regionarnye osobennosti metabolizma strukturno neizmenennogo veshchestva supraventrikuliarnykh prostranstv golovnogo mozga pri remittiruiushchem i vtorichno-progressiruiushchem tipakh techeniia rasseiannogo skleroza.

AIM: To evaluate and compare the intensity of changes in a regional meta-analysis in relapsing-remitting and secondary-progressive multiple sclerosis (RRS and SPMS). MATERIAL AND METHODS: The results of longitudinal studies of multiple sclerosis (MS) using positron emission tomography, magnetic resonance spectroscopy and diffusion tensor imaging are presented. RESULTS: In MS, metabolic changes precede the structural ones. The markers of neuronal and axonal dysfunction (a decrease in NAA/Cr ratios in the white and grey matters, without the structural changes) are recorded in the early stages. The metabolic changes in the grey matter were recorded mostly in the middle frontal gyrus and posterior cingulate cortex. With the increase of duration and severity of MS, the metabolic changes spread to the other regions of supraventricular areas. The distribution of degeneration zones is related to MS course. CONCLUSION: There is substantial evidence on the irreversible damage of neurons in the medial prefrontal cortex in SPMS that confirms the vulnerability of the frontal cingulate gyrus in MS.

Alterations in milk metabolome and coagulation ability during the lactation of dairy cows.

Milk composition has been known to change during lactation. To help understand the changes in metabolic profile throughout the whole lactation, liquid chromatography mass-spectrometry was used to analyze 306 milk samples from 82 primi- and multiparous dairy cows. Changes in metabolic profile common to all cows throughout lactation were ascertained based on principal component and general linear model analysis. Sets of specific markers; for instance, 225, 397, and 641-642 m/z (positive mode), and 186, 241, and 601-604 (negative mode), with at least a 1.5-fold higher intensity during the first 60 d compared with the last 60 d of lactation were observed. The metabolome was affected by parity and milking time. Markers, identified as peptides differentiating parity, were observed. A significant increase for citrate was observed in evening milk. Milk coagulation traits were strongly animal specific. The curd firmness values were influenced by milking time. Sets of markers were associated with curd firmness in positive (197 m/z) and negative (612, 737, 835, 836, 902, 1000, 1038, and 1079 m/z) ion mode.

Alterations in milk and blood metabolomes during the first months of lactation in dairy cows.

The molecular composition of milk is influenced by various genetic and environmental factors. Time is one important factor, and the fact that certain milk components change over the course of lactation is widely accepted. Untargeted global metabolomics is an approach to study hundreds of low molecular weight compounds simultaneously. In this study, mass spectrometry-based global metabolomics was used to follow the course of changes in milk (n=133) and blood plasma (n=133) during the early stage of lactation. Little correlation was found between the molecular composition of blood plasma and milk. Blood showed a higher dependence on animal individuality than did milk, in which common evolutions in time resolved. Citrate and lactose had the greatest effect on these changes; however, the most significant changes in milk during the first months of lactation were associated with phosphorylated saccharide levels, whereas the most significant changes in blood plasma were associated with levels of polyunsaturated fatty acids containing phosphatidylcholine. In conclusion, a new systemic approach was used to search for minor metabolites whose concentrations were significantly altered in milk and blood during the first months of lactation.

Surgical treatment of pleural empyema--changing priorities.

The surgical management of pleural empyema and post-traumatic clotted haemothorax is described. The study included 15 cases of post-thoracotomy empyema, 23 of empyema of other aetiology and five of post-traumatic haemothorax. Chest-tube drainage was the first measure in most cases. Post-pneumonectomy empyema was treated with partial thoracoplasty plus omentoplasty (8 cases) or plus myoplasty (1 case). Empyema after lobectomy or bilobectomy (4 cases) or after failed decortication (1 case) was managed with thoracoplasty or, in cases of concomitant wound infection, with open-window thoracostomy followed by thoracoplasty. Empyema after subclavian artery reconstruction (1 case) was cleared by removal of a previously unrecognized foreign body. For early empyema of other aetiology or haemothorax (10 cases in total), treatment comprised debridement by video-assisted thoracoscopic surgery (VATS). VATS was also used to establish suitable pleural drainage prior to elective thoracotomy (2 cases). Decortication and partial parietal pleurectomy were performed for organizing-stage empyema (16 cases). Three of the 15 patients with post-thoracotomy empyema died perioperatively, one died two months postoperatively and one had recurrence of bronchopleural fistula during follow-up. One patient with VATS debridement subsequently required thoracotomy and lobectomy for lung abscess. All the others with VATS or decortication recovered without complications. During follow-up there was no mortality or recurrence of empyema.

Omentoplasty together with partial thoracoplasty: a one-stage operation for postpneumonectomy pleural empyema.

BACKGROUND AND AIMS: Postpneumonectomy pleural empyema is a rare but life-threatening complication in thoracic surgery. This article describes our treatment strategy of this condition with omentoplasty plus partial thoracoplasty. MATERIAL AND METHODS: During a 2-year period 5, patients were treated. Three patients had clinical signs of bronchial stump fistula confirmed by bronchoscopy and during thoracotomy. Four patients were preoperatively treated with tube thoracostomy and pleural irrigation (median 21 days). In one case no preoperative drainage procedure was used. All patients were treated by partial thoracoplasty and omental transfer as a single-stage operation. Thoracoplasty was performed extrapleurally according to CT findings to reduce the volume of the empyema cavity. Subsequently, the empyema cavity was opened and cleaned. Upper midline incision was used to mobilize omentum majus and transfer it through the diaphragm into the thoracic cavity. RESULTS AND CONCLUSIONS: In 3 patients, the omentum filled the cavity only partially but that did not influence the results. All patients recovered without major complications. Two patients had nausea during the first postoperative days. No recurrence of pleural empyema occurred. Omentoplasty together with partial thoracoplasty is a safe and effective method in the treatment of postpneumonectomy pleural empyema both with and without broncial stump fistula. It can be performed as a single-stage operation without a pre- or postoperative open-window thoracostomy.