Saint Petersburg State Medical University Research Articles

Biomarkers of inflammation and neoangiogenesis in premature rupture of membranes

BACKGROUND: Premature rupture of membranes complicates up to 2–10% of full-term pregnancies and up to 40% of all premature pregnancies. It is believed that the main cause of premature rupture of membranes is inflammation caused by both infectious agents and autoimmune processes. Numerous studies are aimed at searching for biomarkers that can predict inflammation in premature rupture of membranes. AIM: The aim of this study was to determine the levels of pro-inflammatory cytokines such as interleukin-6, -18 and procalcitonin, as well as interferon-α and soluble endoglin, in the blood serum of pregnant women with premature rupture of membranes and women in labor with timely discharge of amniotic fluid and evaluate the possibility of using these parameters to optimize obstetric tactics. MATERIALS AND METHODS: This study included 69 patients delivered at the Clinic of Obstetrics and Gynecology of the Academician I.P. Pavlov First Saint Petersburg State Medical University from January 2022 to March 2023. The main study group consisted of 53 pregnant women with premature rupture of membranes, the control group included 16 women with term labor and timely discharge of amniotic fluid, or amniotomy performed in the first stage of labor. The levels of interleukin-6, -18, interferon-α, procalcitonin and soluble endoglin in maternal peripheral blood were assessed using enzyme-linked immunosorbent assay. Pregnancies complicated by severe preeclampsia, placenta abruption and chronic maternal diseases in the acute stage were excluded from the study. RESULTS: At the time of rupture, the minimum gestational age was 33+0 weeks and the maximum age — 41+3 weeks. The median duration of the anhydrous interval was 31.8 hours. No significant differences in interleukin-6, -18, procalcitonin and soluble endoglin concentrations were revealed in the main and control groups, interferon-α level being higher in the comparison group. The median concentration of interferon-α in pregnant women with premature rupture of membranes was 1.64 pg/ml and in women with timely discharge of amniotic fluid — 4.61 pg/ml (p = 0.001). A weak direct correlation was revealed between soluble endoglin and interleukin-18 concentrations (R = 0.26; p = 0.03), as well as a moderate direct correlation between soluble endoglin and procalcitonin levels (R = 0.4; p 0.001). CONCLUSIONS: The study did not reveal differences in the concentrations of interleukin-6, -18, procalcitonin and soluble endoglin in the comparison groups. A decrease in interferon-α level in the blood in pregnant women increases the risk of developing premature rupture of membranes. The correlations between soluble endoglin and interleukin-18 or procalcitonin concentrations may indicate an association between different mechanisms of the pathogenesis of premature rupture of membranes. In this regard, an integrated approach and analysis of a combination of several cellular bioregulators are eligible to predict infectious complications in premature rupture of membranes.

History of coronary surgery and the role of russian surgeons in its development

Ischemic heart disease is a common disease among the population. Due to the high mortality rate related to this disease, improving its treatment has always been a focal point. cardiologists, along with surgeons, have conducted multidirectional scientific researches for a long time to improve the treatment of acute coronary syndrome. Finally, in 1957, V. P. Demikhov’s experiments on dogs laid the foundation of the treatment of acute coronary syndromes.Taking advantage of this experience, in 1964, V. I. Kolesov managed to restore the impaired blood supply by connect ing the internal mammary artery to the lower part of the coronary artery from the blocked part of the coronary artery in a patient with acute coronary syndrome.This treatment method, which the author called mammary-coronary anastomosis, soon attracted the attention of a number of surgeons around the world who tried to restore the impaired blood supply to the myocardium using this method.The article provides information about researches conducted by distinguished scholars who have made significant contributions to the development of mammary-coronary anastomosis. Also, it offers more detailed information about the role of the renowned surgeon V. I. Kolesov and his school in the development of this treatment method.The refinement of the technique for performing mammary-coronary anastomosis is attributed specifically to the school of V. I. Kolesov. Under his guidance, researches conducted by his students led to the development of the technique for placing mammary-coronary anastomosis using a vascular sewing machine. This also gave rise and justified the idea of performing coronary artery surgery on a beating heart.The article also presents extensive information about a new myocardial infarction model that is suitable for demonstrat ing the dependence of myocardial blood supply restoration through mammary-coronary anastomosis on the duration of coronary artery occlusion. Even so, the article highlights the role of colleagues from the Department of Faculty Surgery № 1 at Pavlov First Saint Petersburg State Medical University in the creation and development of this method.

Reactivation of cytomegalovirus, human herpes virus, and Epstein-Barr virus infections after hemapoietic stem cell transplantation in children

Study objective: to evaluate frequency of CMV, HHV-6, and EBV reactivation in children within 60 days after HSCT.Materials and methods: The study was carried out in Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology, and Transplantation of the Pavlov First Saint Petersburg State Medical University We analyzed 95 medical records of pediatric patients who underwent HSCT in 2021. Pretransplant serostatus for CMV, EBV, HHV-6 was studied, as well as the frequency and timing of virus reactivation after transplantation. In the prospective part, 35 children aged from 1 to 17 years were enrolled. The pretransplant evaluation included detection of anti-CMV, anti-HHV-6, and anti-EBV IgM and IgG by ELISA, and blood PCR for viremia. DNA of herpes viruses was identified by quantitative blood PCR on the day of HSCT, and then 10, 20, 30 and 60 days after HSCT. The number of viral DNA copies was calculated per 105 cells. Statistical analysis was carried out using SPSS Statistics 22 software package.Results: On pre-transplant evaluation, 47 of 95 pediatric patients were tested for CMV with positive result in 36 children, 27 patients were tested for EBV and 17 were positive. HHV-6 DNA was detected in 3 of 25 patientsMostly, reactivation of herpes viruses occurred in the early period up to 60 days. HHV-6 reactivation was observed on average 25±4 days after transplantation, significantly earlier than for CMV and EBV.In a prospective study, reactivation of CMV, HHV-6, and EBV was revealed in 28 (80%) patients within 60 days of transplantation, with a maximum number of patients in 20 days after HSCT.A trend toward an increase in CMV and HHV-6 concentration in blood was observed on days 10 and 20 after HSCT, with a maximum viral load of HHV-6 and minimal EBV replicative activity. Clinically significant manifestations of herpesvirus infection were diagnosed in 19 (54.3%) patients.Conclusion: High seropositivity for CMV and EBV was revealed in children before transplantation. Herpes viruses reactivation occurs early in post-transplant period, on the 20th day after HSCT, HHV-6 in forms of mono- and mixed infection predominates with a trend toward increasing viral load.

The 35th anniversary of the North-Western District center for AIDS prevention and control at the Saint Petersburg Pasteur Institute

The organization of the North-Western District Center for AIDS Prevention and Control (AIDS Center) originates from the onset of the HIV epidemic in the Russian Federation. Over the 35 years of work, the staff of the AIDS Center has made an invaluable contribution to the development of HIV diagnostics, the introduction of new clinical and preventive technologies, patient counseling, and training of qualified personnel. The anniversary article highlights the main stages regarding establishment of the AIDS Center as a structural unit of the Saint Petersburg Pasteur Research Institute. The versatile naturally multidisciplinary functions and tasks related to the AIDS Center organization, its major Russia-wide and global achievements are considered. Special attention is paid to the long-term international cooperation, the results of diverse implemented programs and projects supported by the World Health Organization (WHO) as well as the Joint United Nations Programme on HIV/AIDS. The AIDS Center continues to cooperate with the main scientific facilities such as the Pavlov First Saint Petersburg State Medical University, Institute of Experimental Medicine, N.P. Bekhtereva Institute of the Human Brain of the Russian Academy of Sciences, etc. The ongoing joint research invariably contributes to assessing the epidemiology and clinical course of various viral infections and comorbid conditions. The knowledge acquired becomes regularly summarized and published in a series of monographs, journal articles being presented demonstrated at conferences of various levels. Currently, the AIDS Center is represented by several structural divisions continuing to conduct practical and scientific activities on investigating HIV and viral hepatitis.

A successful second allogeneic hematopoietic stem cell transplantation from an alternative donor in a patient with loss of HLA heterozygosity relapse of juvenile myelomonocytic leukemia: case series analysis

Juvenile myelomonocytic leukemia (JMML) is a rare and aggressive myeloproliferative/myelodysplastic neoplasm of early childhood characterized by activation of the Ras signaling pathway. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only proven curative treatment for JMML. However, the 5-year overall survival is about 52–64%. In this work, we analyzed 4 clinical cases of patients with relapses of JMML with loss of heterozygosity in HLA (LoH) after allo-HSCT. The patients' parents gave their consent to the use of their children's data, including photographs, for research purposes and in publications. Two patients received a second allo-HSCT from an alternative donor, two patients – from the same donor. A positive result in the form of a durable remission was observed in one patient who underwent a second allo-HSCT from an alternative donor and restored HLA genetic heterozygosity. At the same time, immunotherapy with infusions of donor lymphocytes led to the development of graft-versus-host disease without potentiating the antileukemic effect. Thus, a second allo-HSCT from an alternative donor for the treatment of relapsed JMML with HLA LoH is necessary to restore the “graft-versus-JMML” response. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University of Ministry of Healthcare of the Russian Federation.

Premature rupture of membranes: the current state of the problem and approaches to the rational tactics of labor management

Premature rupture of membranes occurs in 220% of all pregnancies. The possibility of identifying risk factors and pre dicting this complication are of great interest in practical obstetrics. This review article highlights the current state of the problem and presents approaches to the rational tactics of labor management in case of premature rupture of membranes. We also present the algorithms for the management of labor in the Obstetrics and Gynecology Clinic, Academician I.P. Pavlov First Saint Petersburg State Medical University.

Molecular genetic and cytofluorimetric prognostic factors in the development of acute myeloid leukemia relapse in children after allogeneic hematopoietic stem cell transplantation

Relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the main causes of reduced long-term survival. Modern methods for predicting the risk of AML relapse after allo-HSCT take into account the data on the pre-transplant level of minimal residual disease (MRD) determined by flow cytometry and molecular biological studies of recurrent genetic abnormalities, which are currently widespread in clinical practice. Recent studies of the expression of genes characteristic of leukemic stem cells (LSCs) have shown prognostic significance for children with AML in relation to treatment response and the risk of relapse. The study of LSC persistence in order to predict the risk of recurrence after allo-HSCT in children with AML in addition to standard MRD detection methods may be of great importance. The aim of the work was to evaluate the impact of MRD status, both using classic methods and taking into account the genes characteristic of LSC, on the results of allo-HSCT in children with AML. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University of Ministry of Healthcare of the Russian Federation. To assess MRD using standard diagnostic methods, we analyzed the data of 95 children with AML in their 1st–2nd remission (cohort 1). MRD status was negative in 67 (70.6 %) patients; in 28 (29.4 %) children, MRD status was positive according to molecular genetic studies and / or immunophenotyping results. For pre-transplant evaluation of the expression of genes characteristic of LSC, we investigated bone marrow samples of 50 patients (cohort 2) using real-time polymerase chain reaction. The DNMT3B, GPR56, CD34, SOCS2, SPINK2, FAM30A, and ABL genes were studied by real-time polymerase chain reaction, followed by calculation of the pLSC6 value using the formula: DNMT3b × 0.189 + GPR56 × 0.054 + CD34 × 0.0171 + SOCS2 × 0.141 + SPINK2 × 0.109 + FAM30A × 0.0516. At the time of allo-HSCT, 37 (74 %) children with AML were in their 1st or 2nd remission of the disease, 13 (26 %) were out of the 1st–2nd remission. With a median follow-up of 5 years in the group of patients with a positive MRD status, determined by standard methods (cohort 1), overall survival (OS) was 67.9 % vs 73.1 % for patients with a negative MRD status (p = 0.83). The cumulative incidence of relapse was 50 % and 22 %, respectively; p = 0.012. When assessing the level of expression of genes characteristic of LSC (cohort 2), a pLSC6 level was above the median in 18/37 (49 %) patients. The results of linear regression showed that the pre-transplant level of expression of genes characteristic of LSC was not associated with the number of blasts/MRD (odds ratio 1.002; 95 % confidence interval 0.979–1.025). One-year OS rates did not differ significantly in children in the 1st–2nd remission of AML, depending on pLSC6 level: 84.2% in patients with low pLSC6 and 72.2 % – with high pLSC6 (p = 0.4), event-free survival in the corresponding groups – 68.4 % and 61.1 %, respectively (p = 0.34). The cumulative incidence of early relapse after allo-HSCT in the group of AML patients with a high pLSC6 score was significantly higher than in children with a low pLSC6 score before allo-HSCT (22 % and 0 %, respectively; p = 0.03). MRD does not have a statistically significant effect on OS. However, MRD positivity before allo-HSCT increases cumulative incidence of relapse. The level of expression of genes characteristic of LSC, determined before allo-HSCT, showed a prognostic significance in relation to the development of early AML relapse after allo-HSCT.

An analysis of the efficacy of graft-versus-host disease prophylaxis with post-transplant cyclophosphamide in children with acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation from HLA-matched and partially-matched unrelated donors

An analysis of the efficacy of graft-versus-host disease prophylaxis with post-transplant cyclophosphamide in children with acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation from HLA-matched and partially-matched unrelated donors

The prognostic value of HLA loss of heterozygosity after allogeneic hematopoietic stem cell transplantation in children with relapsed acute leukemia

The loss of a patient-specific HLA haplotype on the surface of the blast cell population is one of the ways a tumor can evade the immune surveillance of donor cells. This phenomenon is observed in approximately 30 % of relapses in patients with hematologic malignancies who underwent partially mismatched allogeneic hematopoietic stem cell transplantation (HSCT). In this study, for the first time, a large cohort of pediatric patients (n = 80) with relapsed acute myeloid (AML) or acute lymphoblastic (ALL) leukemia after allogeneic HSCT was analyzed with the help of the STR method (highlypolymorphic microsatellite marker analysis) using 6 HLA haplotype markers. The study was approved by the Independent Ethics Committee and the Scientific Council of the I. P. Pavlov First Saint Petersburg State Medical University of Ministry of Healthcare of the Russian Federation. Loss of heterozygosity (LOH) was observed in 18 / 80 (22 %) relapsed patients with various types of acute leukemia: out of these, 8 / 44 (18 %) patients had B-cell ALL, 4 / 10 (40 %) patients – T-cell ALL and 6 / 25 (24 %) patients – AML. All relapses with LOH were observed in patients who had undergone haploidentical HSCT, and were found to occur later than relapses without loss of the HLA haplotype (median time to relapse: 8.8 months vs 6.2 months, p = 0.043). In the patients treated with haploidentical HSCT (n = 61), we assessed factors increasing the risk of LOH at relapse. The number of previous therapy lines in the patients with AML (n = 17) and acute or chronic graft-versus-host disease in the patients with ALL (n = 44) were associated with an increasedrisk of genetic loss of the HLA haplotype (p = 0.008 and p = 0.015 respectively). A relapse following the second allogeneic HSCT was associated with LOH in 4 / 5 (80 %) patients, p = 0.008. The prognosis of the patients with LOH was extremely poor. At a median follow-up of 6 months, the overall survival from relapse was 22 % in the LOH group and 37 % in the non-LOH group. The median overall survival was 4.5 months (95 % confidence interval 3–NA) and 10.3 months (95 % confidence interval 5.7–16.1) respectively, p = 0.063. Among the patients with LOH, the best survival rates were observed in those who had undergone a repeat allogeneic HSCT from a different donor. Thus, the analysis of LOH is an important tool for determining the prognosis and further treatment in pediatric patients with acute leukemias. We strongly recommend that this diagnostic test should be included into standard testing of patients after partially-mismatched allogeneic HSCT.

Best practices in the use of human immunoglobulin preparations for intravenous administration in the treatment of rare neurological diseases

Aim. To describe best practices in using human normal immunoglobulin in patients with immune-mediated neurological disorders according to the data of one clinical center.Materials and methods. From 2016 to 2021, 20 patients with various autoimmune disorders of the peripheral and central nervous system were treated with human normal immunoglobulin at the Neurology Unit No.1 of Pavlov First Saint Petersburg State Medical University. Treatment efficacy was assessed by changes in the neurological examination data according to specialized scales for specific diseases or clinical manifestations (INCAT, QMGS, MoCA, EDSS). Safety of the therapy was assessed considering the instructions to the drug.Results. In the vast majority of patients, treatment allowed to stabilize the course of the disease or was accompanied by pronounced regression.Conclusion. The considered clinical cases of the use of human normal immunoglobulin preparations demonstrate the possibility of their use in the treatment of a number of autoimmune neurological diseases for unregistered indications.

Роль стационарного отделения скорой медицинской помощи в условиях массового поступления пострадавших в техногенных чрезвычайных ситуациях

Summary. Investigation purpose – a planning of stationary department of urgent medical treatment (SDUMT) work in conditions of massive influx of technogenic emergencies (ES) victims. Methods and materials of the investigation. To make the virtual models of (SDUMT) the Flexsim HealthCare software was chosen. The software allows to conduct a processive modeling of predictable work. A work of two stationary urgent medical treatment departments was recreated. The first was SDUMT of university clinic of the First Saint-Petersburg state medical university (FSPAMU) named after academic I.P. Pavlov of Ministry of Health of Russia (model-1) with average (23±2 patients per day) patient influx. The second was SDUMT of city urgent medical treatment hospital №25 of the city of Volgograd (model 2) with average (145±3 patients per day) patient influx. In addition, a retrospective analysis of technogenic ES happened in 45 Russian subjects in 2017-2022 was conducted. A prognosis of specified SDUMT work in conditions of massive emergency victims influx was planned to conduct basing on the up written analysis. Investigation results and their analysis. As a result of the experiments an optimal SDUMT staff was defined. The role of this staff in conditions of massive technogenic emergency victims influx was assessed.

Cerebrovascular complications of hematopoetic stem cell transplantation in patients with hematologic malignancies

Introduction. Modern transplantation and biological therapy methods are associated with a wide range of adverse events and complications. Incidence and variety of neurological complications mostly depend on myelo- and immunosuppression severity and duration as well as on donor's and recipient's characteristics. The most frequent complications involving the nervous system include neurotoxic reactions, infections, autoimmune and lymphoproliferative diseases, and dysmetabolic conditions as well as cerebrovascular complications that potentially affect transplantation outcomes.
 Objective. To evaluate the impact of post-transplantation cerebrovascular events (CVEs) on transplantation outcomes in patients with hematologic malignancies.
 Materials and methods. We analyzed 899 transplantations performed at the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology, and Transplantation, Pavlov First Saint Petersburg State Medical University, from 2016 to 2018. We assessed transplantation parameters and donor's and recipient's characteristics by intergroup comparison, pseudo-randomization (propensity score matching), KaplanMeier survival analysis, and log-rank tests.
 Results. Post-transplantatively, CVEs developed in 2.6% (n = 23) of cases: 13 (1.4%) ischemic strokes and 11 (1.2%) hemorrhagic strokes or intracranial hemorrhages were diagnosed. CVEs developed on days 99.5 39.2 post hematopoetic stem cell transplantation (HSCT). There were more patients with non-malignant conditions in the CVE group as compared to the non-CVE group (21.7% vs 7.9%; p = 0.017). Patients with CVE had a significantly lower Karnofsky index (75.6 21.3 vs 85.2 14.9; p = 0.008). Statistically, we also note some non-significant trends: patients with CVE more often underwent allogenic HSCT (82.6% vs 64.0%; p = 0.077) while donors were more often partially (rather than totally) HLA compatible for recipients (39.1% vs 21.1%; p = 0.33). Patients with CVE more often had a history of venous thromboses (13.3% vs 4.2%; p = 0.077). Post-HSCT stroke decreased post-transplantation longevity by approximately 3 times (331.8 81.6 vs 897.9 25.4 post HSCT; p = 0.0001). In the CVE group, survival during first 180 days post HSCT (landmarks post-HSCT Day+60 and Day+180) was significantly lower as compared to that in the CVE-free group. If CVE developed during first 30 days and 100 days post HSCT, vascular catastrophe did not affect post-HSCT survival significantly.
 Conclusion. Whereas ischemic stroke is a long-term HSCT complication (beyond D+100 post transplantation), hemorrhagic stroke is a short-term complication (D0D+100 post HSCT). CVEs affect survival in patients with hematologic malignancies, especially those developed between D+60 and D+180 post HSCT. History of venous abnormalities, low Karnofsky index at HSCT initiation, and the type of allogenic HSCT, especially from half-matched donors, can be considered as negative outcome risk factors in post-HSCT CVE.

Immunotherapy of high-risk infant acute lymphoblastic leukemia using blinatumomab and infusion of donor lymphocytes

Pleuropulmonary blastoma (PPB) is a very rare tumor of childhood that arises from the mesenchyme of the lung and is associated Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. Despite intensified therapy protocols, infant ALL remains a difficult-to-treat disease, with a high relapse rate. Allogeneic bone marrow transplantation is the only curative method aimed to curing the disease. Over the last decades, donor lymphocyte infusion (DLI) has been used as a salvage therapy after post-transplant relapses in B-ALL patients with a proven antileukemic effect. The combination of blinatumomab and DLI is a promising immunoadoptive therapy for resistant ALL based on the induction of “graft versus leukemia” effect by activating donor T-lymphocytes. We analyzed the results of combined immunoadoptive therapy with a bispecific T-cell activator blinatumomab and DLI in 3 infants with ALL, as well as the outcome of monotherapy with a bispecific T-cell activator in one infant. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University. All infants initially had the KMT2A gene rearrangement and were classified as high-risk. The indication for immunoadoptive therapy was an early combined relapse of the disease after haploidentical hematopoietic stem cell transplantation in one patient and minimal residual disease (MRD) in three patients. All patients achieved long term hematological remission of the disease, 3 (75%) patients – MRD negative remission. The median duration of bone marrow response was 24 (8–63) months. One patient developed a bone marrow relapse in 8 months after therapy, two patients developed isolated extramedullary relapse. We did not see toxic complications and induction of graft-versus-host disease during immunoadoptive therapy. At the time of the follow up, all patients are alive, three remains in lasting hematological remission.

Characteristics of genetic changes in the <i>SMN1</i> gene in spinal muscular atrophy 5q

Background. Proximal spinal muscular atrophy 5q (5q‑SMA) is one of the most common neuromuscular diseases, which is caused by mutations of the SMN1 gene. Despite the fact that most studies consider SMN1 “deletion” as the most common cause of 5q‑SMA, gene loss is in fact associated with both classical deletions and conversions of SMN1 and SMN2, as well as with formation of chimeric structures. Up to now, far too little attention has been paid to the prevalence of types of SMN1 loss. However, different types of mutations can have different influence on the clinical findings and the effectiveness of therapy. A deeper study of the structure of these genes will allow us to determine the predictors of response to treatment and bring us closer to understanding the reasons for the instability of the SMN region.Aim. To study genetic changes in the SMN1 gene, as well as the number of copies of the SMN1 and SMN2 genes in 5q‑SMA.Materials and methods. The study involved 703 patients, for whom the analysis of the number of copies of SMN1 and SMN2 was performed in the center of molecular medicine of I.P. Pavlov First Saint Petersburg State Medical University for 2018–2021. Gene copy number analysis was performed by multiplex ligation‑dependent probe amplification (MLPA) using the SALSA MLPA P021 SMA kit (MRC Holland).Results. Among 703 participants, a homozygous SMN1 deletion was found in 167 (24 %), 76 (11 %) were carriers of the deletion and no aberrations were found in the remaining 460 (65 %). Among patients with a homozygous deletion, 41 (24 %) cases of a true deletion were identified. Also, 11 (7 %) cases of partial deletion with a homozygous loss of the 7th exon and heterozygous of the 8th exon of SMN1 were identified. The most common type of aberration was the conversion of SMN1 to SMN2 – 94 (56 %) cases, which is characterized by a homozygous loss of SMN1 and a reciprocal increase in SMN2 copies. In addition, 21 (13 %) cases of the formation of hybrid genes were found.Conclusion. Types of genetic aberrations in 5q‑SMA have not been studied enough yet. A search of the literature revealed very few studies which results are comparable with ours. However, further research of genetic changes in SMN1 and SMN2 might bring more clarity on the causes and mechanisms of this disease, and get us closer to finding the most effective method of treatment.

About the first gastric surgeries performed in Saint Petersburg in the ХIХ century

The article is devoted to the history of gastric surgery in Saint Petersburg (Russia) in the XIX century. In the last decades of the 19th century, there was a breakthrough in surgery - surgeons from all over the world began to operate on the stomach. For the first time in Saint Petersburg and in Russia, Russian surgeons M.K. Kitaevsky, D.M. Monastyrsky and N.V. Ekk performed stomach resection for cancer by Billroth I method (M.K. Kitaevsky, 16.07.1881) and gastroenteroanastomosis for cicatrical pyloric stenosis (N.D. Monastyrsky, 13.03.1882), and at the meeting of the Society of Russian Doctors in Saint Petersburg in May 1882, V. Ekk proposed to overlap an anastomosis between the stump of the resected stomach and the loop of the small intestine that was realized by the Viennese surgeon T. Billroth only 3 years later in 1885, and got the name of the modification of gastric resection by the Billrot II method. It should be noted that M.K. Kitaevsky and N.D. Monastyrsky worked at Petropavlovsky Hospital - on the basis of which the Women's Medical Institute was established in 1897 (now the Pavlov First Saint Petersburg State Medical University).

Stroke before a haematopoietic stem cell transplantation is a potential risk factor for poor response to therapy in patients with blood cancer

Introduction. More than 50,000 haematopoietic stem cell transplantations (HSCTs) are performed worldwide each year to treat malignant blood cancers, solid tumours, bone marrow aplasia, primary immunodeficiency conditions, autoimmune disorders, and storage disorders. The success of HSCTs depends on many factors, including patient's past medical history.
 Purpose. To assess the effect of an acute cerebrovascular accident (CVA) that occurred before the HSCT on the transplantation outcome in patients with blood cancer.
 Materials and methods. We examined the results of 899 transplantations conducted between 2016 and 2018 at the R.M. Gorbacheva Research Institute for Pediatric Oncology, Haematology and Transplantation of the Pavlov First Saint Petersburg State Medical University. We analysed transplantation parameters, as well as donor and recipient characteristics. Apart from intergroup comparisons, pseudo-randomization was performed using the Propensity Score Matching method. The survival rate analysis was conducted using the KaplanMeier estimate and the log rank test.
 Results. Sixteen patients (1.8%) had cerebrovascular events in their past history before the HSCT: ischaemic stroke in 0.4% of cases and haemorrhagic stroke or intracerebral haemorrhage in 1.4% of cases. Patients with a history of cerebrovascular events included more people with leukaemia (p = 0.02), had more often received an allogenic transplant (р = 0.01), the donors more often had a partial rather than a full HLA match with the recipient (р = 0.06), had a lower body mass index (р = 0.02), and a lower Karnofsky/Lansky score (р = 0.01) than patients in the control group. The presence of a cardiovascular event had a statistically significant association with reduced overall survival rate of HSCT recipients (р = 0.0012).
 Conclusion. Patients with blood cancer and stroke preceding the transplantation do not typically have any 'classical' risk factors (diabetes mellitus, venous system disorders, decreased cardiac output, significant atherosclerotic changes in precerebral arteries), therefore, secondary prevention guidelines for CVA during treatment of the main disease may not be effective and cannot be relied on. This article discusses the most likely causes of CVA in patients with blood cancer. A history of CVA before HSCT may have a significant effect on the transplantation outcome, but is not a contraindication for this treatment method. Recipient selection is a very important stage in HSCT planning. A multidisciplinary team should find a balance between the indications and contraindications for performing HSCT from an unrelated donor.

Autologous hematopoietic stem cell transplantation in children with relapsed or refractory Hodgkin lymphoma

The majority of patients with Hodgkin lymphoma (HL) are cured, which represents one of the best cure rates in oncology. However, the prognosis is not as favorable in case of relapsed or refractory (RR) disease. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective way to consolidate remission in patients with RR HL. Despite the many years of experience and the availability of results of randomized trials confirming the efficacy of high-dose chemotherapy in adults, the role of auto-HSCT in children with HL has not been studied as extensively, and there are only a limited number of publications on the subject. As is the case with the majority of other pediatric tumors, RR HL is a rare entity, which is why it is so difficult to study it. Here we share the experience of the R. M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation in auto-HSCT in children and adolescents with HL. The study was approved by an Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint-Petersburg State Medical University. We included 54 patients with RR HL who had undergone auto-HSCT during the period from 2007 to 2021. Refractory disease (n = 29; 54 %) was diagnosed in case of HL progression either during first-line therapy or in the first 3 months after the completion of the treatment. Relapsed disease was diagnosed in 25 (46 %) children. Early HL relapse (< 12 months since the start of therapy) was evident in 18 (72 %) patients, while late HL relapse (≥ 12 months since the start of therapy) occurred in 7 (28 %) children. The median number of lines of therapy before auto-HSCT was 3 (1–6). The first line of treatment was chemotherapy in accordance with the GPOH-HD (n = 27; 50 %), BEACOPP (n = 19; 35 %), or other protocols (n = 8; 15 %); the second line involved the use of IEP/ABVD (n = 14; 27 %), DHAP (n = 12; 23%), ICE (n = 13; 25 %), or other combinations (n = 13; 25%); and third-line treatment consisted of DHAP (n = 9; 29 %), a combination of brentuximab vedotin and bendamustine (n = 8; 26%), immune checkpoint inhibitors (ICIs) (n = 7; 22.5 %) or other regimens (n = 7; 22.5 %). ICIs were used for remission induction prior to auto-HSCT in 14 (26 %) patients. Response was assessed using the Lugano classification. Status before transplantation: complete remission (CR) – 21 (39 %) patients, partial remission (PR) – 30 (56 %), disease stabilization – 2 (3.5 %), disease progression – 1 (1.5 %). The BEAM conditioning regimen was used in 17 (31 %) patients, and the BeEAM regimen – in 32 (59 %) patients. The 3-, 5- and 10-year overall survival (OS) was 88% (95 % confidence interval (CI) 74–95), 80% (95 % CI 62–90) and 63% (95 % CI 34–81) respectively. The 10-year progression-free survival (PFS) was 46% (95 % CI 24–65). The median follow-up was 3.3 (0.1–12.3) years. The long-term PFS in children with CR and PR was 72% (95 % CI 41–89) and 33 % (95 % CI 8–61) respectively (p = 0.067). A total of 9 (16.7 %) patients died during follow-up. The main cause of death was progressive HL (n = 6), while some patients died in the early post-transplant period due to infections (n = 3; 5.6 %). The median time to relapse or progression after auto-HSCT was 6 (1–77) months. Out of 17 (31 %) patients with relapsed or progressive HL after auto-HSCT, 9 (53 %) children are alive at a median follow-up of 2.3 (0.7–9) years. Considering that our study included patients who had been more extensively pre-treated (the median number of lines of therapy – 3) than patients in the majority of other studies (the median number of lines of therapy – 2), it can be assumed that our results are superior to historical data. The improvement of transplantation outcomes observed over time can be attributed to better supportive treatment and probably, to the use of immunotherapy. According to the Center for International Blood and Marrow Transplant Research (CIBMTR), it is crucially important that long-term survival in children with RR HL be monitored closely since it can be drastically different from results obtained during the first years of follow-up - due to late relapses and complications of the received treatment. The 10-year survival rates show that the RR HL problem is yet to be resolved. With the help of auto-HSCT, approximately half of children and adolescents with RR HL can be cured. One of the most important favorable prognostic factors in these patients is the achievement of CR before transplantation. The use of immunotherapy for remission induction before auto-HSCT is also promising.

Review on the monograph of Doctor of Medical Sciences Professor V.I. Strashnova «Development of the anesthesiology and intensive care at the Pavlov First Saint Petersburg State Medical University, Saint Petersburg, 2021

The monograph is devoted to the history of anesthesiology at the Pavlov First Saint Petersburg State Medical University. In the first chapter titled The beginning of the epoch of anesthesia, the author emphasized the role of coryphaeus. Russian world surgeon and anesthesiologist, Nikolay I Pirogov, enumerated the merits of Vasily von Anrep, the first rector of the womens medical institute who discovered the local anesthetic property of cocaine. The second chapter, Development of anesthesia: from 1918 to 1950, shows the role of Professors V.A. Shaak, L.A. Andreev, K.K. Skrobansky, and A.A. Zykov. The third chapter, Development of Anesthesiology: from 1945 till 1970, describes the beginning of the application of the apparatus method of general anesthesia and the first dissertations in anesthesiology. The fourth chapter, Development of Anesthesiology and Intensive Care since 1971, describes the establishment of the Department of Anesthesiology and Intensive Care in 1974 and the results of its scientific work, particularly the role of epidural anesthesia in the anesthesiological support of lung surgery, the development of combined spinalepidural anesthesia, and the establishment of a new direction - adrenergic analgesia. The fifth chapter, Development of Anesthesiology and Intensive Care since 2001, includes data about monographs and is written by the department staff. The sixth chapter, Development of Anesthesiology since 2013, shows the changes in the educational activities of the department and the challenges of providing emergency care to individuals with various qualifications. The monograph will be useful for students, clinical residents, practical physicians, and historians of medicine.

Past 7th All-Russian Congress of Manual Medicine

The All-Russian Congress of Manual Medicine has been held in St. Petersburg in April 8-10, 2022. The thematic scientific forum has been held in accordance with the charter of the All-Russian Association of Manual Medicine and has been dedicated to the most important dates in Russian medicine. The Congress has celebrated the 100th anniversary of the birth of Viola Fraiman, the founder of osteopathy in the Russian Federation, and the 85th anniversary of Aleksandr Anisimovich Skoromets, head of the Department of Neurology, Pavlov First Saint-Petersburg State Medical University, honorary president of the All-Russian Association of Manual Medicine, member of the Russian Academy of Sciences.

History and prospects of perinatal mortality rate in Russia

Population reproduction is a priority task of social policy and a factor of Russias national security. The review presents the stages of recording the perinatal mortality indicator, which is closely related to the frequency of preterm birth. In the first stage, the criteria for registering preterm birth were 28 weeks of pregnancy, and in the second, since 2012, 22 weeks. At both stages, due to underreporting of low birth weight babies (their transfer to the miscarriage group), stillbirths, including full-term babies, prevailed in the preterm birth indicator structure. The authors of the article stressed that the main cause of preterm birth (including iatrogenic) is the formation of endotoxemia syndrome, or systemic effects of aggressive metabolites in the mother placenta fetus system. In this etiopathogenetic therapeutic means are methods of efferent therapy in the form of plasmapheresis, etc. These technologies in many obstetric pathologies (thrombophilia, preeclampsia, Rh-conflict, isthmic-cesmic and chronic placental insufficiency, etc.) sanitize the mother placenta fetus system and allow to prolong pregnancy with a reduction of perinatal mortality index. The authors cite their own data on the use of efferent therapy methods in 102 women presenting at 2228 weeks of pregnancy to the Perinatal Center of Saint Petersburg State Medical University from other institutions after unsuccessful treatment according to the Protocols for various obstetric complications. Pregnancies were prolonged by 215 weeks; all 123 children (20 twins, 1 triplet) were born alive, did not require long-term intensive care, survived and were not disabled. Six newborns died and the perinatal mortality rate was 48 : 1000, which is an order of magnitude lower than that quoted in the literature for similar pathologies and gestational ages. In conclusion of the article, it is suggested that in order to reduce perinatal mortality in Russia, all large institutions should arrange efferent therapy rooms to treat sick pregnant women using the safe, low-cost technologies developed by the authors, using domestic equipment.