[Association of cardiovascular disease with hospital mortality in COVID-19 patients].

AIM: To evaluate the relationship between the in-hospital mortality of patients with COVID-19 and the history of cardiovascular disease (CVD) using data from the Russian registry of patients with COVID-19. MATERIAL AND METHODS: This study included 758 patients with COVID-19 (403 men, 355 women) aged from 18 to 95 years (median, 61 years), successively hospitalized in the COVID hospital of the Chazov National Medical Research Center of Cardiology from April through June 2020. Death predictors were studied using single- and multivariate regression analyses with the SPSS Statistics, Version 23.0 software. RESULTS: During the stay in the hospital, 59 (7.8 %) patients with COVID-19 died, 677 (89.3 %) were discharged, and 22 (2.9 %) were transferred to other hospitals. The univariate regression analysis showed that the increase in age per decade was associated with a 92% increase in the risk of death [relative risk (RR), 1.92; 95% confidence interval (CI), 1.58-2.34; p <0.001], and an increase in the number of CVDs increases the risk of death by 71% (RR 1.71; 95% CI 1.42-2.07; p<0.001). The presence of one or more CVDs or specific diseases [atrial fibrillation, chronic heart failure (CHF), ischemic heart disease, myocardial infarction, history of cerebrovascular accidents], as well as diabetes mellitus were associated with a higher risk of fatal outcome during the hospitalization for COVID-19. The presence of any CVD increased the risk of in-hospital death by 3.2 times. However, when the model was adjusted for age and sex, this association lost its strength, and only the presence of CHF was associated with a 3-fold increase in the risk of death (RR, 3.16; 95 % CI, 1.64-6.09; p=0.001). Age was another independent predictor of death (RR, 1.05; 95 % CI, 1.03-1.08; p < 0.001). CONCLUSION: A history of CVD and the CVD number and severity are associated with a higher risk of death during the hospitalization for COVID-19; the independent predictors of in-hospital death are an age of 80 years and older and CHF.

[Vaginal leiomyosarcoma in pregnancy]. / Leiomiosarkoma vlagalishcha u beremennoi.

The article presents a rare clinical observation of a vaginal tumor detected during pregnancy, which prevented delivery through the natural birth canal and caused a cesarean section at full term. According to the primary biopsy at 34 weeks, neurofibroma was diagnosed. In the postpartum period, due to profuse bloody discharge, the patient was admitted to the Moscow Regional Research Institute of Obstetrics and Gynecology for surgical treatment, where, according to the results of a morphological study of the removed tumor, vaginal leiomyosarcoma was diagnosed.

[Fetal mediastinal teratomas. Report of two cases]. / Teratomy sredosteniya ploda. Opisanie dvukh nablyudenii.

Teratomas are one of the most common tumors diagnosed in fetuses and newborns. In this age group, extragonadal teratomas predominate, among which the mediastinum ones accounts for up to 15% of teratomas of the perinatal period. They may be associated with the thymus or thyroid gland; in some cases a clear connection with adjacent organs cannot be identified. Teratomas of the heart, also localized in the mediastinum, are often considered separately from the mediastinal ones; most often the tumor affects the pericardium. The article describes two cases of mediastinal teratomas detected by ultrasound in the second trimester of pregnancy, with signs of rapid growth and compression symptoms typical for this localization of the tumor - hydropericardium and other manifestations of non-immune fetal hydrops. In both cases, immature teratomas (grade 2 and 3) were diagnosed with a predominance of immature neuroectodermal tissue, as well as with the presence of endoderm derivatives, including areas of the hepatoid structure, microglandular structures and cysts lined with mucus-forming epithelium. The mesodermal component was represented by hyaline cartilage. An immunohistochemical study revealed an extremely high proliferative activity in the immature neuroectodermal component - more than 90% of positive nuclei were detected in the neuroepithelium upon reaction with Ki67 antibodies. In all other tissue elements, proliferative activity was low.

[Twin gestation with regressive partial hydatidiform mole and coexisting live fetus]. / Nerazvivayushchiisya chastichnyi puzyrnyi zanos v slitnoi dikhorial'noi platsente s normal'nym razvitiem vtorogo bliznetsa.

The case of dichorionic twin pregnancy is described, with a fused placenta, one part of which is represented by a tissue of partial hydatidiform mole (PHM) with signs of regression, the second part is a placenta of a common structure with a normal development of the second twin. The delivery took place at the term of 38 weeks with a live healthy girl weighing 3250 g. A single placental disc consisted of two fused placentas with a clear boundary between them. The placenta of a live-born girl was mature, with focal chorangiosis, the second part of the disc was represented by the PHM tissue with avascular giant bizarre villi, some of them with central cisterns, with stromal fibrosis, low proliferative activity of the villous trophoblast and a significant narrowing of the intervillous space. A genetic study was carried out on the material of paraffin blocks from two parts of the placental disc containing the tissue of the villous chorion, and the blood of the parents. Comparative analysis of DNA isolated from the paraffin block of PHM with the DNA of the parents revealed the presence of diandric dispermic triploidy. No chromosomal pathology was found in the placenta of a living girl. For hydatidiform mole in the case of multiple pregnancy, an increase in the volume of the affected placenta is characteristic compared to the normal placenta of the twin. In our observation, the presence in the placenta with PHM signs characteristic of placentas with antenatal fetal death, stromal fibrosis of the villi and low proliferative activity of the trophoblast suggests a regression of PHM.

[Uterine vascular abnormalities]. / Sosudistye anomalii matki.

Congenital and acquired vascular abnormalities of the uterus are quite rarely, but they are given much attention in the scientific literature due to the risk of life-threatening bleeding. In the uterus, as in any other organs, malformations can involve vessels of any caliber and type. The review summarizes the materials by clinical characteristics, pathogenesis, diagnostic methods, morphological features and management tactics of patients with uterine arteriovenous malformations. Enhanced myometrial vascularity in the puerperium due to retained placental tissue are also considered. The issues of terminology and differential diagnosis of these conditions are discussed, which is important in connection with significantly different approaches to treatment.

[Perinatal lethal Gaucher disease. Case report]. / Perinatal'nyi letal'nyi variant bolezni Goshe. Opisanie nablyudeniya.

The paper describes a case of a perinatal lethal Gaucher disease in a 29-week-old fetus with non-immune hydrops, facial dysmorphia, hepatosplenomegaly, and hypoplasia of cerebellum and pons. Gaucher cells were found in the lymph nodes, spleen, lungs, thymus, cerebellum, and bone marrow. No storage cells have been detected in the placenta. There was a significant placental weight increase due to swelling. The diagnosis of Gaucher disease was confirmed by biochemical analysis (deficiency of glucocerebrosidase activity and sharply increased hexanoylsphingosine concentration) and molecular genetic techniques (the presence of two mutations of the GBA gene). Our observation shows that characteristic histologic signs of disease can be detected at early stages of development.

[Uterine adenosarcoma. Report of 5 cases and review of literature]. / Adenosarkoma matki. Opisanie pyati nablyudenii i obzor literatury.

Uterine adenosarcoma is an uncommon biphasic tumor with benign epithelial and malignant mesenchymal components, often presenting difficulties for morphological diagnosis. We describe 5 cases of adenosarcoma of the uterine corpus and cervix, and vaginal stump in patients aged 46-76 years. Clinical data, ultrasound results, morphological data, including immunohistochemical studies with antibodies to CD10, estrogen and progesterone receptors, desmin, smooth muscle actin, and Ki-67 are presented. Large polypoid mass of the epithelial-mesenchymal structure within the uterine cavity in women of peri - and postmenopausal age require the exclusion of malignancy of the mesenchymal component with searchig for diagnostic criteria - periglandular cuffing of the stromal cells and mitoses.

Clinical Characteristics and Factors Associated with Poor Outcomes in Hospitalized Patients with Novel Coronavirus Infection COVID-19.

Aim      To evaluate the clinical picture and factors associated with unfavorable outcomes in admitted patients with COVID-19.Material and methods This study included all patients admitted to the COVID Center of the National Research Center of Cardiology of the Russian Ministry of Health Care from May 1 through May 31, 2020. Clinical demographic, laboratory, and instrumental indexes and associated factors were studied with one-way and multivariate logistic regression analysis.Results This study included 402 patients aged 18 to 95 years (mean age, 62.9±14.6 years); 43.0 % of them were older than 65 years. COVID-19 was frequently associated with chronic comorbidities, including arterial hypertension (74.4 %), obesity (41.6 %), history of ischemic heart disease (12.9 %), atrial fibrillation (18.9 %), type 2 diabetes mellitus (DM) (13.0 %), and oncological diseases (9.2 %). 13.0 % of patients were smokers; less than 10% had chronic lung diseases. 3.9% of patients had a combination of COVID-19 and acute coronary pathology, including acute myocardial infarction (MI) in 3.2 % (13) and unstable angina in 0.7 % (3). The most frequent clinical manifestation of COVID-19 were four symptoms: cough (81.1 %), weakness (80.3 %), shortness of breath (71.6 %), and fever (62.7 %). 46.5% of patients had shortage of breath and chest pain/compression, 40.3% had headache, 31.1% had myalgia, 28.8% had anosmia, and 25.5% had ageusia. Arterial oxygen saturation was <93.0 % in 55.7 % of cases. According to laboratory blood tests the patients had anemia (58.2 %), lymphopenia (34.8 %), neutropenia (19.2 %), thrombocytopenia (11.9 %), and increased levels of high-sensitivity C-reactive protein (hsCRP, 87.3 %), interleukin-6 (89.3 %), ferritin (62.1 %), and D-dimer (49.2 %). 56.2% of patients required various regimens of oxygen support. 83 (20.6%) patients were admitted to intensive care and resuscitation units; invasive artificial ventilation was performed only for 34 (8.5 %) patients. In-hospital mortality was 7.7 % (31 / 402). One-way regression analysis identified major factors associated with death during the stay in the hospital: age >55 years, NEWS scale score >4.0, oxygen saturation <92.0 %, blood glucose >5.4 mmol/l, hs-CRP >25.7 mg/l, and creatinine clearance <72.0 ml/min. Furthermore, the risk increased with increasing degree of changes in each factor. According to results of the multivariate regression analysis, three most significant predictors of the hard endpoint, all-cause death during the stay in the hospital, were more than 5-fold increases in aspartate aminotransferase and/or alanine aminotransferase compared to normal levels (relative risk (RR) 16.8 at 95 % confidence interval (CI) 5.0-56.3, р<0.001), pronounced changes in the lungs consistent with a CT-4 picture as shown by computed tomography (CT) (RR 13.4; 95 % CI 3.9-45.5, р<0.001), and MI/unstable angina during the stay in the hospital (RR 11.3; 95 % CI 1.4-90.6, р=0.023). The probability of death was also considerably increased by chronic obstructive pulmonary disease, impaired kidney function (creatinine clearance estimated by Cockcroft-Gault <60.0 ml/min), type 2 DM, oncological diseases, and dementia.Conclusion      This study established factors associated with unfavorable outcomes in admitted patients with COVID-19. This will allow identifying in advance patients with a high risk of complications that require increased attention to take more active diagnostic and therapeutic measures at prehospital and hospital stages.

[Persistent gestational trophoblastic disease following ectopic molar pregnancy]. / Persistiruyushchaya gestatsionnaya trofoblasticheskaya bolezn' posle polnogo puzyrnogo zanosa pri ektopicheskoi sheechnoi beremennosti.

A case of persistent gestational trophoblastic disease that developed after ectopic (cervical) pregnancy with complete hydatidiform mole (CHM) in a 56-year-old patient is presented. The diagnosis of CHM was made retrospectively based on immunohistochemical analysis of archival material using p57 and Ki67 antibodies. Observation shows the difficulty of objective diagnosis of hydatidiform mole in early pregnancy due to the lack of typical cystic transformation of the stroma of villi, focal proliferation of villous trophoblast. Application of the p57 marker for the differential diagnosis of CHM and other variants of cystic villi transformation may be especially important in cases of ectopic pregnancy, in which morphological changes in the chorion do not always correspond to the classical picture. The presence of ectopic pregnancy with CHM in a 56-year-old patient requires special attention of clinicians.

[Metastatic leiomyoma or synchronous lesion of the uteri corpus and vulva?] / Metastaziruiushchaia leiomioma ili sinkhronnoe porazhenie tela matki i vul'vy?

OBJECTIVE: To reveal the morphological characteristics of simultaneously diagnosed leiomyoma of the corpus uteri and vulva. SUBJECT AND METHODS: The paper describes a case of multiple uterine leiomyomas concurrent with vulvar leiomyoma in a 39-year-old patient with progressive tumor nodule growth over 2 years. Vulvar tumor was biopsied simultaneously with extirpation of the uterus; vulvar leiomyoma was removed six months later. Histological and immunohistochemical studies: such as hematoxylin and eosin staining, the expression of smooth muscle actin, desmin, and progesterone and estrogen receptors, S100, CD10, and determination of Ki-67 proliferation index, were conducted. RESULTS: The largest (14-cm) multiple tumor nodule in the corpus uteri had the structure of leiomyoma of uncertain malignant potential; the large (8-cm) vulvar tumor was a leiomyoma with hyalinosis. The immunohistochemical profile of uterine and vulvar leiomyoma (smooth muscle actin+, desmin+, progesterone+, estrogen+ receptors, CD117-, and Ki-67) was the same (1-3%). The vulvar leiomyoma was assumed to be a tumor of metastatic origin. CONCLUSION: Vulvar leiomyoma is rare; it can arise from smooth muscle tissue of various anatomical structures of the skin and soft tissues. The pathogenesis of the so-called metastatic leiomyoma is unclear; there are concepts of a metaplastic transformation of subcelomic mesenchyme and multifocal smooth muscle proliferation. The presented case demonstrates the synchronous development of uterine and vulvar leiomyoma.

[Placental mesenchymal dysplasia]. / Mezenkhimal'naia displaziia platsenty.

OBJECTIVE: To carry out a clinical and morphological analysis of 6 cases of placental mesenchymal dysplasia (PMD) that is not associated with Beckwith-Wiedemann syndrome. MATERIAL AND METHODS: Medical records, placental macroscopic and microscopic changes, histochemical (MSB staining) and immunohistochemical studies of placental tissue with antibodies against p57, CD34, smooth muscle actin, desmin, and Ki-67 were analyzed. RESULTS: Vascular anomalies in the chorionic plate and stem villi, the increased size and edema of the stem villi during normal formation of the terminal branches of the villous tree, the lack of proliferation of villous trophoblast were the typical signs of PMD and were noted in all cases. Comparison of the results of ultrasonography with the morphological pattern of the disease suggested that there were ultrasound signs that were typical of PMD. The characteristics of the course and outcomes of pregnancy in PMD were given. The features of morphological changes in the presence of PMD concurrent with preeclampsia were found. Significant variability in p57 expression in PMD was shown and variants of changes given. There were no substantial features of the expression of desmin and smooth muscle actin in PMD. CONCLUSION: MDP has typical morphological and ultrasound signs. The significant variability in the levels of chorionic gonadotropin and alpha-fetoprotein and in the expression of p57 does not allow their use in the differential diagnosis of PMD. The high incidence of thrombotic events in the intervillous space and fetal vessels, as well as intrauterine growth restriction, intrauterine hypoxia, and an impaired neonatal adaptation period in PMD should be taken into account when determining the management tactics for female patients and newborns.

[Features of the pathogenesis of the placenta growing in the scar after cesarean section]. / Osobennosti patogeneza vrastaniia platsenty v rubets posle kesareva secheniia.

OBJECTIVE: to investigate the structural and pathogenetic features of pathological placental attachment in the scar after cesarean section. MATERIAL AND METHODS: The investigators explored 12 uteri; 11 of which were removed with placentas at 9 to 38 weeks' gestation (one in the first trimester, three at 18-22 weeks, two at 32-35 weeks, and five at 37-38 weeks); one uterus was removed after an artificial abortion at 12 weeks' gestation in the scar, as well as the scars excised in the first trimester in non-developing (n=4) and progressive (n=2) pregnancies. For histological examination, fragments of the full-thickness uterine wall were taken from the placental bed in different areas. The sections were stained for fibrin with hematoxylin and eosin, van Gieson stain, and the Martius scarlet/blue (MSB) technique. Decidual tissue, trophoblast, vascular component, and smooth muscle tissue were identified by an immunohistochemical assay using antibodies to vimentin, pan-cytokeratin, vascular endothelium (СD31), and smooth muscle actin. RESULTS: In most cases, placental localization in the scar after cesarean section was accompanied by abnormal placental attachment: almost always placenta accreta, less frequently in combination with its ingrowth (placenta accreta/increta). The morphological substrate of placenta increta was a change in the content and ratio of normal histological components in the uterine wall, such as the mucosa, smooth muscle tissue, and vessels (the absence or thinning of decidual tissue and the myometrium, as well as its cicatricial changes). The structural criterion for placenta increta was necrosis of the walls of the large veins in the myometrium due to the replacement of their intermediate trophoblast and fibrin and to the destruction of vessel walls, leading to prolapse of the chorionic villi into the veins. CONCLUSION: In most cases, placental localization in the scar after cesarean section is accompanied by abnormal placental attachment: placenta accreta, less frequently in combination with its ingrowth (placenta accreta/increta).

[Twin pregnancy with complete hydatidiform mole]. / Polnyi puzyrnyi zanos pri beremennosti dvoinei.

The paper describes a case of twin pregnancy with complete hydatidiform mole (CHM). According to the data available in the literature, the concurrence of CHM with a normal placenta and a viable fetus occurs in 1 per 20,000-100,000 pregnancies, requires a differential diagnosis with partial hydatidiform mole and placental mesenchymal dysplasia, and is characterized by a high rate of complications. In this concurrence, the frequency of persistent trophoblastic disease is as high as 50%. In this case, the pregnancy ended in a spontaneous abortion at 16-17 weeks of pregnancy. A morphological examination determined the fetus without congenital malformations with normal placental weight and structure and the adjacent intact placental tissue with the macro- and microscopic signs of CHM. The diagnosis was confirmed by the lack of р57 expression in the villous trophoblast and stroma in the tissue of the hydatidiform mole. The patient was diagnosed with persistent trophoblastic disease at 2 months after the abortion.

[Placental alterations in pregnant women with autoimmune polyglandular endocrinopathy].

The paper gives the results of a morphological study of 13 placentas from patients with rare autoimmune polyglandular syndrome and adrenal insufficiency, a disease history of 2 to 14 years, receiving corticosteroid replacement therapy. All pregnancies were full-term; labors were term surgical. The clinical and morphological associations suggest the placental alterations characteristic of diabetes mellitus, autoimmune diseases, uteroplacental and placentofetal ischemia.

[Osteoporosis and arterial stiffness: study of 103 women with mild to moderate risk of cardiovascular disease].

OBJECTIVE: to evaluate the relationship between arterial stiffness and bone metabolism in women with mild to moderate risk of cardiovascular disease (CVD). METHODS: In 103 postmenopausal women (mean age 57.0 years, 95% CI 50.0-64.0) with mild to moderate risk of CVD (SCORE<5), no more than mild hypertension, normal function of thyroid gland, without coronary artery disease, diabetes mellitus and secondary causes of osteoporosis pulse wave velocity between carotid and femoral sites (cfPWV, by applanation tonometry) and ankle and brachial sites (baPWV, by volume sphygmography) as well as bone mineral density at lumbar spine and femoral neck (by dual-energy X-ray absorptiometry) and blood serum levels of markers of bone turnover (total procollagen type I amino-terminal propeptide (PINP), osteocalcin, collagen type 1 cross-linked C-telopeptide (-CTX) by electrochemilumininescence immunoassay) were assessed. RESULTS: Compared with patients with normal mineral bone density (BMD) (n=27), patients with osteoporosis (n=31) had higher cfPWV and baPWV values (p<0.05). Patients with osteopenia did not differ from other groups (p>0.05). In osteoporosis group there were greater years since menopause, less body mass index than in normal BMD (in all cases p<0.05; ns between osteoporosis and osteopenia groups). Between all three groups there were no significant differences in age, smoking status, visit blood pressure, lipid levels and medication. CfPWV and baPWV values significantly positively correlated with age, systolic arterial pressure, years since menopause, procollagen type I N propeptide (all p<0.05), and significantly negatively correlated with BMD at hip neck (all p<0.05). Relationship between cfPWV and BMD at lumbar spine did not reach significant value (r=-0.18, p=0.068). No relationship was found between parameters of arterial stiffness and CTX and osteocalcin (all p>0.05). In the multivariate analysis cfPWV was significantly and independently associated with systolic blood pressure (=1.03, 95% CI 1.00-1.06, p=0.03) and BMD at hip neck (=0.01, 95% CI 0.001-0.07, p=0.003). CONCLUSION: Revealed association between arterial stiffness and bone metabolism may probably explain general mechanisms of arterial and bone damage in postmenopausal women with mild to moderate risk of cardiovascular disease.

[Massive subchorial thrombosis].

Massive subchorial thrombosis (MSCT) is a placental abnormality, the etiology and pathogenesis of which remain inadequately studied. MSCT is characterized by a clinical symptom complex comprising marked intrauterine growth retardation, oligohydramnios, and fetal distress due to placental circulatory problems. Perinatal outcomes are appreciably determined by the term of pregnancy, the degree of placental insufficiency, and neonatal status. Prolonged MSCT makes it possible to diagnose this pathology by echographic and magnetic resonance imaging studies and to attempt to treat placental dysfunction through tocolytic therapy and correction of oligohydramnios, to prolong pregnancy, and to have a viable newborn infant. The clinical and morphological diagnosis of MSCT calls for its differential diagnosis with other focal placental lesions, such as subamniotic, intraplacental, and retroplacental hematomas, cytotrophoblastic cyst, umbilical cord cysts, and chorangioma.

[The problem of study of unexplainable antenatal fetal death].

The paperpresents the data on the causes ofperinatal mortality. Particular emphasis is placed on unexplainable antenatal fetal death, the absence of uniform terminology or a consensus classification of the causes of antenatal fetal death, and the principles in placental studies and stillborn baby autopsy. Various aspects of sophisticated relations in the mother-placenta-fetus system are considered. It is pointed out that the number of unexplainable antenatal fetal deaths can be reduced when the placenta is meticulously studied. A conventional protocol for stillborn baby autopsy and placental studies is noted to be elaborated.

[Diabetic fetopathy in gravida with autoimmune hemolytic anemia complicated by steroid diabetes].

The authors made a clinicoanatomic analysis of fetal death in a 32-year-old diabetic gravida at 34-35 weeks gestational age. Fetal autopsy identified the characteristic signs of fetopathy: macrosomy, cardiomegaly, hepatomegaly, and brain weight reduction. Histological analysis revealed minute foci of leukomalacia with glial proliferation in the cerebral hemispheres; adipose and hyaline drop degeneration of cardiomyocytes in the heart, that of hepatocytes in the liver, the proximal renal tubular epithelial cells; hemorrhages in the respiratory portions of the lung. The pancreas displayed inflammation foci, hypertrophy and hyperplasia of the islets of Langerhans. Immunohistochemical studies identified cells with enlarged nuclei among the beta and alpha-cells. The placenta showed a large mass with pronounced changes. It has been demonstrated that steroid diabetes may lead to the development of diabetic fetopathy and placental changes, which are typical of maternal diabetes.

[Assessment of major artery stiffness: new perspectives of noninvasive diagnosis of coronary atherosclerosis].

AIM: Arterial stiffness is a predictor of atherosclerosis. This study was conducted to develop a method of coronary atherosclerosis severity assessment by means of brachial-ankle pulse wave velocity (baPWV). MATERIAL AND METHODS: We measured baPWV in 119 males (age 51.67 +/- 7.25) who received coronary angiographic examination (CAG). The baPWV was measured by Vasera VS-1000 (Fukuda Denshi). RESULTS: The patients were divided into two groups by severity of stenosis (group 1--less than 50% stenosis, group 2 > 50%). The baPWV value was significantly greater in group 2 (n = 98, baPWV 13.15 +/- 2.14 m/s, p = 0.004) than that in group 1 (n = 21, baPWV 12.13 +/- 1.17 m/s). ROC-curve demonstrated that the best cut-off point of the baPWV for predicting occlusive atherosclerosis was 12.2 m/s. The area under ROC-curve was 0.66 (p = 0.034). An univariate binary logistic regression model demonstrated that only baPWV had a significant odds ratio for coronary stenosis > 50%: 2.68 (95% CI = 1.01-7.15), p = 0.043. Other risk factors were not significantly associated with severity of stenosis. CONCLUSION: The baPWV significantly reflects the severity of stenosis in middle-aged males opening new perspectives of noninvasive detection of coronary artery atherosclerosis in middle-aged males.