[Challenges of expert assessment of injury to health in the case of iatrogenic mastectomy due to erroneous histological verification of an oncological condition]. / Problemy ekspertnoi otsenki vreda zdorov'yu v sluchae yatrogennogo udaleniya molochnykh zhelez vsledstvie oshibochnoi gistologicheskoi verifikatsii onkologicheskoi patologii.

A case of commission forensic medical examination in the St. Petersburg Bureau of Forensic Science of a civil case due to an unfavorable treatment outcome is presented. Patient T., 45 years old; due to erroneous histological verification of oncological pathology, she had both breasts removed and received antitumor treatment. It has been shown that defects in histological diagnosis can lead to errors by clinicians and become the subject of lawsuits by patients accusing healthcare professionals of adverse treatment outcomes. It is emphasized that the current legislation lacks medical criteria and an algorithm for assessing the severity of injury to health in women with one or both breasts removed.

[Problems of expert assessment of a case of fatal rupture of the wall of the rudimentary horn of the uterus in ectopic pregnancy]. / Problemy ekspertnoi otsenki sluchaya fatal'nogo razryva stenki rudimentarnogo roga matki pri ektopicheskoi beremennosti.

Recently in the Russian Federation there has been a significant increase in the number of commissions of forensic medical examinations on «medical cases¼ associated with inappropriate provision of medical care to the population. The problem of investigating such crimes is one of the most difficult tasks facing law enforcement agencies. A special place among them is occupied by examinations related to maternal mortality. Bleeding is one of the main causes of maternal mortality, the share of which in Russia in 2019 was 14.5%. An illustrative example of conditionally preventable death is the case of an unfavorable outcome of a pathological pregnancy in patient A., 25 years old, which ended in a sudden spontaneous rupture of the rudimentary horn of the uterus with massive intra-abdominal bleeding. The underestimation of the results of MRI and ultrasound diagnostics led to a medical error in establishing the variant of an anomaly in the development of the uterus in patient A. and entailed the wrong tactics for managing her pregnancy under observation in a private medical organization.

Cause of death based on systematic post-mortem studies in patients with positive SARS-CoV-2 tissue PCR during the COVID-19 pandemic.

IMPORTANCE: Assessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD). METHODS: Consecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post-mortem SARS-CoV-2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels. RESULTS: COVID-19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID-19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID-19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID-19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis. CONCLUSIONS: Vast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.

[Tropical malaria with a fatal outcome]. / Tropicheskaya malyariya s letal'nym iskhodom.

Tropical malaria is an acute infectious disease from a group of parasitic diseases transmitted by the vector-borne route. Russia registers deaths due to imported malaria. The paper gives brief information on the epidemiology, etiology, and clinical manifestations of the disease and describes the fatal outcome of cerebral tropical malaria, as well as morphological changes in organs and tissues. The K76T mutation associated with drug resistance in parasites was identified in the structure of the plasmodium gene.

[Anatomical pathology of novel coronavirus (COVID-19) infection. First impressions]. / Patologicheskaya anatomiya novoi koronavirusnoi infektsii COVID-19. Pervye vpechatleniya.

To date, descriptive results of a clinical and morphological study of novel coronavirus COVID-19 infection, mainly of the lungs, have appeared. However, in other organs, primarily in the cardiovascular system, there are substantial structural changes that lead to multiple organ dysfunction and contribute to death. OBJECTIVE: To analyze the thanatogenetic significance of novel coronavirus COVID-19 infection in different age and gender groups and to describe the main morphopathological manifestations in various organs. MATERIAL AND METHODS: The investigators carried out a comprehensive analysis of 700 autopsies of people disease from the novel coronavirus COVID-19 infection, which included an examination of gross changes reflected in the autopsy protocols and forensic medical examination reports, as well as that of microscopic changes detected during histological examination of organs. Immunohistochemistry (IHC) using mouse or rabbit antibodies to CD34, CD68, EMA, Ki67, caspase-3, and VEGF was employed in some observations. RESULTS: The novel coronavirus COVID-19 infection was the primary cause of death. Acute respiratory and pulmonary heart failure and multiple organ dysfunction became the leading thanatogenetic mechanisms in COVID-19. Cardiovascular disease, diabetes mellitus, and obesity were the most common diseases in patients with COVID-19. The most pronounced lung changes in COVID-19 were determined with a predominance of multiple total bilateral lesions of the lower lobes of the lungs, which was manifested by virus-induced changes in the parenchyma and stroma, as well as by microcirculation disorders. Acute dyscirculatory and ischemic changes in the parenchymal organs dominated in tissue damage caused by the virus. CONCLUSION: The changes in different organs of those who have died from the new coronavirus COVID-19 infection are stereotyped and include the manifestations of virus-induced action and a systemic inflammatory response with mainly microvasculature alteration, which leads to the development of coagulopathies and, accordingly, to total hypoxia.

[COMPLEXITIES IN THE DIFFERENTIAL DIAGNOSIS OF MULTIPLE SCLEROSIS AND HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (CLINICAL CASE)].

Demyelinating diseases of the central nervous system in children are characterized by the complexity of differential diagnosis and require an integrated approach using laboratory and instrumental studies. The clinical observation of a child with gradually progressing neurological symptoms and the presence of focal changes in the brain demonstrates the difficulty of differential diagnosis between demyelinating disease, neuroinfection and hematologic disease (hemophagocytic lymphohistiocytosis), which initialized with CNS damage. The article presents the tactics of etio-pathogenetic treatment of a patient during differential diagnosis with the use of cytoflavin in complex therapy as a multi-factor drug that allows to stabilize the patient's condition.

[Difficulties of differential diagnosis of organic injury of the nervous system in children]. / Trudnosti differentsial'noi diagnostiki organicheskogo porazheniia nervnoi sistemy u detei.

The growth of organic lesions of the central nervous system (CNS) in children, clinical polymorphism, the similarity of clinical and laboratory parameters in inflammatory, demyelinating and oncological diseases necessitate careful differential diagnosis. The clinical case presented in the article confirms the difficulties of differential diagnosis of organic CNS lesion in children, and therefore it is urgent to expand the indications for a brain biopsy, which will allow to timely diagnose correctly, avoid an erroneous diagnostic search and develop adequate tactics.

[Clinical and morphological correlations in occult hepatitis B]. / Kliniko-morfologicheskie sopostavleniia pri okkul'tnom gepatite B.

Occult hepatitis B (ОHB) characterized by the absence of blood HBsAg attracts the attention of specialists of different profiles; however, its clinical morphological aspects have not been practically studied. AIM: to estimate the proportion of OHB in the structure of fatal outcomes in chronic viral hepatitis (CVH) and to characterize its clinical course and structural changes on autopsy materials. MATERIAL AND METHODS: A total of 455 autopsy cases of CVH were examined for its etiology in the S.P. Botkin Clinical Hospital of Infectious Diseases in 2014-2016. An in-depth prospective clinical analysis was made to investigate 28 cases of OHB in the stage of decompensated liver cirrhosis, which had subsequently culminated in death. The criteria of inclusion were history data and clinical symptoms of CVH in the detection of markers for hepatitis A, C, and D and HIV in serum HBcAb in the absence of HBsAg. HBsAbs were also determined. Along with the traditional morphological examination, immunohistochemistry (IHC) for HBsAg and HBcAg was carried out. RESULTS: There were 108 CVHB cases (23.7% of the total cases of CVH), including 77 OHB cases (71.3% of those of CVHB) while HBsAg was not determined. HBsAb-negative patients were more often observed to have clinical signs of jaundice (p<0.05) and skin itching (p<0.05). Dyspepsia and hemorrhagic manifestations prevailed in patients with HBsAb (more than 10 IU/l) (p<0.05). All the cases were found to have characteristic morphological signs of CVH, including intranuclear inclusions and nuclear polymorphism in 10.7% of deaths. There was an IHC-positive reaction to VHB antigens in 28.6% of the patients and a doubtful reaction in 25.0%. CONCLUSION: Serum НВсAb may serve as a diagnostic marker for HBV infection. Clinical and morphological correlations enabled the authors to state that CVHB was present in all cases in the absence of serum HBsAg in the patients.

[CLINICAL AND MORPHOLOGICAL CHARACTERISTICS OF INTESTINAL LESIONS IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS].

Objective: To compare the clinical, endoscopic picture and morphological changes of the intestinal mucosa in patients with primary sclerosing cholangitis (PSC). Materials and methods: 31 patients with PSC (women - 15 men - 16) were included in study group. The diagnosis of ulcerative colitis (UC) was established in 8 patients, Crohn's disease (CD) - in 5, unclassified colitis (UCC) - in 7, and 11 patients had no clinical and endoscopic signs of IBD. The control group consisted of 30 patients with IBD: UC - 20 patients, CD - 10 persons. All the patients performed ileocolonoscopy (ICS) with multiple biopsy and histological examination of material. Results: The prevalence of IBD in patients with PSC was 64.5%. IBD with PSC was characterized by extensive colitis with mild clinical activity. Morphological activity of IBD associated with PSC was usually moderate and severe. Morphological activity of disease in IBD/PSC group was lower than in UC alone (p < 0.05). IBD onset came before PSC symptoms (p < 0.05). Distal gradient of inflammation in colon predominated in IBD/PSC group when disease starts with IBD symptoms, in case of PSC symptoms - proximal gradient was more frequent. In IBD/PSC group affected ileum were detected in a third of cases, including CD ileitis - 60%, backwash ileitis in UC (NCC) in 26.7%, that was significantly frequently than in UC alone (p = 0.02). Within the IBD/PSC group 30% of patients with colitis were without damaging of rectum. In all the patients with PSC without clinical, endoscopic signs of colitis polymorphocellular infiltration of mucosa were founded. Eosinophilic infiltration of mucosa in group of PSC met significantly more frequently than in other study groups. Fibrosis of intestinal mucosa was founded significantly more frequently in group of PSC without IBD compared with UC/PSC and UC patients, but not with CD group. Conclusions: For IBD in PSC extensive colitis without lesions of the rectum, backwash ileitis are common. There are some morphological differences in the intestinal lesions within the IBD/PSC patients depending on the type of disease onset. There is a dissociation between low clinical activity and intensive morphological inflammation. When PSC had no clinical features of IBD, a microscopic ileocolitis (characterized by eosinophilic infiltration and fibrosis of the intestinal mucosa) without nosological classification was founded in all patients.

[Morphological diagnosis of tuberculosis under present-day conditions].

The paper presents general statistical data on morbidity and mortality rates of tuberculosis, which show positive trends in recent years, with exception of those of its concurrence with HIV infection. The tasks of the morphological diagnosis of tuberculosis are divided into 4 groups: 1) to refine approaches to detecting mycobacteria in tissues; 2) to optimize the postmortem diagnosis of tuberculosis; 3) to optimize the lifetime differential diagnosis of tuberculosis and to develop methods for predicting its course; 4) to study the pathogenesis of tuberculosis from the standpoint of modern views on an infectious process. The data suggesting that the tissue forms of mycobacteria, the types of inflammatory responses, and the specific features of the pathogenesis of tuberculosis call for further investigations are given. To establish the real role of nontuberculous mycobacteria, to study the likelihood that the patient will be superinfected with other M. tuberculosis genotypes, and to elaborate a uniform (clinical, pathogenetic, and morphological) classification of tuberculosis should be also regarded as the most important tasks in its morphological examination.

[Generalized pneumocystosis in HIV infection].

The paper describes a rare case of rapidly progressive generalized pneumocystosis in HIV infection in a 43-year-old patient who died 4.5-5 months after disease onset. The specific feature of the case is that in pneumocystosis there was multiple organ dysfunction, as well as infiltrate decay to form small and large lung cavities similar to tuberculosis ones. Autopsy disclosed Pneumocystis-induced changes in the liver, spleen, lymph nodes, and the wall of the ileum. Pneumocystosis and HIV infection were diagnosed only posthumously. The specificity of organ diseases was immunohistochemically verified.

[Fas, FasL, and bcl-2 expression on hepatic intralobar lymphocytes in different variants of the natural course of chronic HBV and HCV infection and in its outcomes].

The investigation revealed the specific features of cell-mediated hepatocyte damage in different variants of the natural course of chronic HBV and HCV infection and in its outcomes (chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma), by determining the expression of proapoptotic (Fas, FasL) and antiapoptotic (bcl-2) factors on the surface of intralobular lymphocytes. Comparative analysis of the magnitude and pattern of cell infiltration in the liver parenchyma, the functional activity of intralobular lymphocytes showed significant differences in the above indicators in relation to the etiology and stage of the pathological process, suggesting that there were different pathogenetic mechanisms of their natural course. There was a varying potential readiness of intralobular lymphocytes for apoptosis, giving rise to different clinical manifestations in the similar morphological picture.

[Evaluation of the placental morphofunctional state in perinatal HIV transmission].

The paper presents the results of investigating the mechanisms of placental insufficiency and transplacental infection of infants born to HIV-infected mothers who have received specific antiretroviral therapy mothers and who have not.

[Role of transforming growth factor-beta in the development of some liver diseases].

AIM: To investigate the expression of transforming growth factor-beta 1 (TGF-beta1) in the liver tissue of patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and chronic hepatitis C (CHC). MATERIALS AND METHODS: Liver biopsy specimens were histologically and immunohistologically examined in 37 patients with verified liver diseases (12 with AIH, 15 with PBC, and 10 with CHC). RESULTS: The expression of TGF-beta1 in the non-parenchymal liver cells of the patients with AIH and PBC with liver cirrhosis was statistically significantly higher than in those without the latter (p = 0.01 and p = 0.04, respectively). There was a positive relationship between the stage of fibrosis and the absolute content TGF-beta1 and CD68+ cells in the portal tracts (r = 0.51). The higher expression of TGF-beta1 was found in the patients with HCV and AIH than in those with PBC (p = 0.03 and p < 0.05, respectively). There were no differences in the expression of TGF-beta1 in the patients with AIH as compared to those with CHC (p = 0.55). The number of CD68-positive macrophages was higher in CHC than in AIH and PBC (p = 0.004 and p = 0.01, respectively). In autoimmune liver diseases, TGF-beta1 was mainly expressed by the macrophages located in the portal tracts and, in CHC, within the hepatic lobules. CONCLUSION: The enhanced TGF-beta1 expression in the nonparenchymal liver cells in AIH and PBC with liver cirrhosis confirms the role of this cytokine in development of fibrosis in autoimmune liver diseases. That in hepatitis of various etiologies versus PBC suggests that the TGF-beta1 signaling pathway may play an important role in an inappropriate immune response in hepatitides; and the variations found in the location of the macrophages expressing TGF-beta1 reflect a difference in the mechanisms of lesions.

[Mesenchymal dysplasia of heart valves, cystic medianecrosis of the aorta and herpetic infection].

Histologic and immunohistochemical studies (use of antibodies for viruses of herpes simplex type 1 and 2, desmin, vimentin, SMA as well as polymerase chain reaction to DNA of viruses of herpes simplex) were made on the material of the valves taken from 1326 patients with valvular heart disease, the ascending aorta of 30 patients with aneurysm, valves of 35 deceased patients without cardiovascular pathology. As a result, expression of viruses of herpes simplex type 1 and/or 2 was found in all cases with mesenchymal dysplasia and cystic medianecrosis in endotheliocytes, fibroblasts, smooth muscle cells of valves and aorta. This indicates the role of these viruses in the pathogenesis of these diseases and their common etiology.

[Clinical and molecular correlation between chronic hepatitis and hepatocellular carcinoma induced by hepatitis B virus].

The role of X-gene of hepatitis B virus (HBV), telomerase gene, structural HBV proteins is considered. Both factors of the virus and those of the host are involved in hepatocarcinogenesis. The duration of chronic B hepatitis may influence mitogenic and mutagenic conditions for accumulation of occasional genetic and chromosomal damage and result in hepatocarcinoma development.

[Pathological anatomy of HIV infection according to data in Saint-Petersburg]. / Patologicheskaia anatomiia VICh-infektsii po materialam Sankt-Peterburga.

The results of postmortem investigation of 101 cases of HIV infection at its different stages in Saint-Petersburg are analyzed. The challenges to a pathologist performing the autopsy are discussed. There has been an increase in the number of deaths since 2000, among drug users in particular. Macrophacytic transformation and specific HIV-related encephalitis are among the most important changes directly associated with immunodeficiency virus. Among secondary infections, cryptococcosis, cytomegaly, pneumocystosis, and tuberculosis are most common and significant.

[Mesodiencephalic modulation (transcranial electrostimulation of the brain) in neurology and psychiatry]. / Mezodiéntsefal'naia moduliatsiia (transkranial'naia élektrostimuliatsiia golovnogo mozga) v nevrologii i psikhiatrii.

The paper outlines the results of mesodiencephalic modulation (MDM) as therapy in adults and children with neurological and mental diseases in the out- and inpatient setting. MDM is a method of transcranial electric therapy that normalizes the performance of the hypothalamohypophyseal and opioid systems of the brain, which ultimately improves the body's adaptive response in disease.

[Relationship between chronic viral hepatitis and hepatocellular carcinoma]. / Sviaz' khronicheskogo virusnogo gepatita i gepatotselliuliarnogo raka.

Recent years have seen a correlation between the rise in morbidity and lethality from chronic viral hepatitis and that of hepatocellular carcinoma. Present-day methods of hepatotropic viruses (HBV and HCV) identification point to a growing role of chronic viral hepatitis in etiology of cirrhosis which gives rise to hepatocellular cancers. A study of 49 cases based on sectional material established hepatocellular carcinoma development in smoldering chronic viral hepatitis caused by B or C virus or their combination. An immunohistochemical investigation (29) identified differences in hepatitis B and C virus antigen expression in tumor and adjacent hepatic tissue.