Lethal Cases Research Articles

Minimally invasive adrenalectomy – Operative and perioperative results of transperitoneal and retroperitoneal adrenalectomies performed at the University of Szeged Department of Surgery during 23 years

Aim. Our goal was to evaluate operative and perioperative data of retroperitoneal (RP) and transperitoneal (TP) adrenalectomies performed at the University of Szeged Department of Surgery. Patients and method. During aretrospective cohort study including 174 adrenalectomies (28 RP; 146 TP) performed between 1998 and 2021, the following parameters were evaluated: rate of previous abdominal surgeries, conversion rate, operative time, intraoperative blood loss, tumor size, histology, hospital stay, early and late complications. Results. With significantly higher rate of previous abdominal surgeries [TP vs RP: 68 (46.57%) vs 4 (14%)P= 0.0021], there was no markable difference in conversion rate [TP vs RP: 7 (4.79%) vs 5 (18%),P= 0.312]. Significantly larger tumours were removed with TP (TP vs RP: 58.05 vs 34.8 mm,P= 0.016), with no markable difference in intraoperative blood loss (TP vs RP: 67.85 vs 50.2 ml,P= 0.157). Operative time was significantly shorter in TP (TP vs RP: 86.3 vs 134.5 min;P= 0.024). The most frequent histology was adenoma (TP vs RP:n= 95; 65.06% vs 64.3%). Pheochromocytoma occurred in 11 (7.53%) and 5 (17.8%) cases in TP and RP, respectively. We found no significant difference in hospital stay (TP vs RP: 5.125 vs 4.61 day;P= 0.413). Five- and 2 cases of early complications were seen in TP (splenic injury, postoperative fever, severe intraoperative bleeding, severe hypokalemia, surgical site infection) and RP (2 severe intraoperative bleeding), respectively. One lethal case of ventricular fibrillation and one delayed complication (postoperative abdominal wall hernia) were observed in TP. Conclusions. Both TP and RP are safe and simply reproducible minimally invasive techniques. According to our observation, RP adrenalectomy seems to be reserved for smaller lesions, while TP proves to be successful in removing enlarged and also malignant lesions with significantly shorter operative time.

SARS-CoV-2-Induced Pathology-Relevance to COVID-19 Pathophysiology.

In spite of intensive studies of different aspects of a new coronavirus infection, many issues still remain unclear. In a screening analysis of histopathology in l200 lethal cases, authors succeeded in performing a wide spectrum of immune histochemical reactions (CD2, CD 3, CD 4, CD 5, CD 7, CD 8, CD14, CD 20, CD 31, CD 34, CD 56, CD 57, CD 68, CD 163, collagen 1,3, spike protein SARS-CoV-2, caspase-3, MLCM; ACE2 receptor, occludin, and claudin-1 and -3) and electron microscopy. The results of the histological and IHC studies of deceased people with varying degrees of severity of coronavirus infection confirmed the ability of these pathogens to cause cytoproliferative changes, primarily in epithelial and endothelial cells. Lesions of various organs are possible, while the reasons for significant differences in organotropy remain unclear. Severe respiratory failure in COVID-19 in humans is associated with a very peculiar viral pneumonia. In the pathogenesis of COVID-19, the most important role is played by lesions of the microcirculatory bed, the genesis of which requires further study, but direct viral damage is most likely. Endothelial damage can be associated with both thrombosis in vessels of various calibers, leading to characteristic complications, and the development of DIC syndrome with maximal kidney damage. Such lesions can be the basis of clinically diagnosed septic shock, while usually there are no morphological data in favor of classical sepsis caused by bacteria or fungi. A massive infiltration of the lung tissue and other organs, mainly by T lymphocytes, including those with suppressor properties, makes it necessary to conduct a differential diagnosis between the morphological manifestation of the protective cellular immune response and direct viral lesions but does not exclude the hypothesis of an immunopathological component of pathogenesis. In many of the deceased, even in the absence of clear clinical symptoms, a variety of extrapulmonary lesions were also detected. The mechanism of their development probably has a complex nature: direct lesions associated with the generalization of viral infection and vascular disorders associated with endothelial damage and having an autoimmune nature. Many aspects of the pathogenesis of coronavirus infection require further comprehensive study.

A paediatric dysembryoplastic neuroepithelial tumour (DNET) with deregulated stem cell markers: a case report

BackgroundDysembryoplastic neuroepithelial tumours (DNETs) are rare, with only a few reported lethal cases. Currently, there are focused efforts by neuro-oncology professionals to reveal the molecular characterisations of individual central nervous system tumours (CNSTs). Here, we report the status of cancer stem cell (CSC) genes associated with resilience and drug resistance in a paediatric DNET, since the deregulations and variations of CSC genes may prove critical to these tumours’ molecular characterisations.Case DescriptionImmunofluorescence, clonogenic assay and whole exome sequencing (WES) were applied to the patient’s tissue and its corresponding cell line. The case is for of a 6-year-old boy with intractable epilepsy and unremarkable physical and neurological examinations. Following magnetic resonance imaging (MRI) and histopathological tests, the patient was diagnosed with DNET. The child underwent a right posterior temporoparietooccipital neuronavigation-assisted craniotomy. Several CSC markers were upregulated in situ, including the metastasis-related protein, anterior gradient 2 (AGR2; 67%), and the Wnt-signalling-related protein, frizzled class receptor 9 (FZD9; 79%). The cell line possessed a similar DNA profile as the original tissue, stained positive for the tumorigenic marker [BMI1 proto-oncogene (BMI)] and CSC markers, and displayed drug resistance. Variants identified in the tissue DNA, which are listed in the catalogue of somatic mutations in cancer (COSMIC) database for genes previously known to be necessary for the development of the embryonic brain, included variants in the cell division cycle 27 (CDC27) gene.Conclusionswe report the in situ and in vitro presence of CSCs in a paediatric DNET.

Suppression of Pituitary Hormone Genes in Subjects Who Died From COVID-19 Independently of Virus Detection in the Gland

ContextInvolvement of the pituitary gland in SARS-CoV-2 infection has been clinically suggested by pituitary hormone deficiency in severe COVID-19 cases, by altered serum ACTH levels in hospitalized patients, and by cases of pituitary apoplexy. However, the direct viral infection of the gland has not been investigated.ObjectivesTo evaluate whether the SARS-CoV-2 genome and antigens could be present in pituitary glands of lethal cases of COVID-19, and to assess possible changes in the expression of immune-related and pituitary-specific genes.MethodsSARS-CoV-2 genome and antigens were searched in the pituitary gland of 23 patients who died from COVID-19 and, as controls, in 12 subjects who died from trauma or sudden cardiac death. Real-time RT-PCR, in situ hybridization, immunohistochemistry and transmission electron microscopy were utilized. Levels of mRNA transcripts of immune-related and pituitary-specific genes were measured by the nCounter assay.ResultsThe SARS-CoV-2 genome and antigens were detected in 14/23 (61%) pituitary glands of the COVID-19 group, not in controls. In SARS-CoV-2 positive pituitaries, the viral genome was consistently detected by PCR in the adeno- and the neurohypophysis. Immunohistochemistry, in situ hybridization and transmission electron microscopy confirmed the presence of SARS-CoV-2 in the pituitary. Activation of type I interferon signaling and enhanced levels of neutrophil and cytotoxic cell scores were found in virus-positive glands. mRNA transcripts of pituitary hormones and pituitary developmental/regulatory genes were suppressed in all COVID-19 cases irrespective of virus-positivity.ConclusionOur study supports the tropism of SARS-CoV-2 for human pituitary and encourage to explore pituitary dysfunction post-COVID-19.

Clinical characteristics of SARS-COV-2 associated lethal pneumonia in pregnant women

Aim. To reduce maternal mortality by examining the clinical features of the course of lethal SARS-COV-2-associated pneumonia in pregnant women to further optimize diagnosis, obstetric management, and treatment.Material and Methods. 70 pregnant women were examined: 34 (48.6%) with moderate, 11 (15.7%) with severe, and 25 (35.7%) with extremely severe SARS-CoV-2. The scope of the study corresponded to the standard examination of pregnant women with SARS-CoV-2 coronavirus infection. Of the total number examined, 7 cases (1%) were fatal.Results and discussion. The main symptoms of lethal cases of pneumonia, which manifested from the first days of the disease and progressed rapidly were: an increase in body temperature to febrile values from the beginning of the disease - 7 (100%), marked weakness - 7 (100%), increasing dry and unproductive cough - 7 (100%). Increasing dyspnea and tachypnea on admission to the hospital were also determined in all pregnant women who died. Chest pain predominated in the majority, 4 (57.1±20.2%) of the pregnant women who died. The symptoms of intoxication were pronounced and manifested as arthralgia - 4 (57.1±20.2%), myalgia - 3 (42.9±20.2%), headache - 3 (42.9±20.2%). Toxic lesion of the cardiovascular system was manifested by tachycardia in 7(100%) and hypotension in 4 (57,1±20,2%) cases.Conclusion. The combination of febrile fever, low-productive cough, increasing dyspnea, and tachypnea should be considered as specific clinical symptoms of lethal SARS-CoV-2-associated pneumonia in pregnant women in the second half of gestation.

Analysis of the Epidemiological Situation on the Pneumonia with Signs of Coronavirus Infection among the Population of the Republic of Kazakhstan

New coronavirus infection caused by SARS-CoV-2 (COVID-19), as well as pneumonia with signs of coronavirus infection, continues to spread around the world, but the epidemiological situation is not the same in different countries.
 The aim of the study: to analyze the epidemiological situation of coronavirus infection and pneumonia with signs of coronavirus infection in the Republic of Kazakhstan.
 Material and methods of the research: retrospective epidemiological analysis of the incidence of coronavirus infection and pneumonia with signs of coronavirus infection in the republic according to official statistical reporting, as well as a statistical analysis of discharge records of patients diagnosed with coronavirus infection (no virus identified) in a small town of Karaganda region was carried out.
 Results: An increase in cases, sick persons, recovered persons and lethal cases in population with positive PCR for COVID-19, as well as pneumonia with signs of coronavirus infection in the Republic of Kazakhstan was registered for the period from 08/01/2020 to 12/31/2021. The number of cases of coronavirus increased in 10.93 time, those who recovered – in 15.78 times, deaths – in 16.4 time, respectively. The increase in the number of cases of pneumonia with signs of coronavirus infection also increased in 16.24 time, the number of those who recovered at the beginning of the observation was not established, by the end the number of recovered was 76,989 people, the number of deaths increased in 173.83 time.
 Conclusion: An analysis of the discharge records of patients with pneumonia with signs of coronavirus infection revealed that 54.2% of the patients were females and 45.8% were males. The disease was registered in 21.8% of patients older than 60 years in the presence of concomitant diseases. Concomitant diseases were represented in 42% by arterial hypertension, in 26% by ischemic heart disease, in 14% by pyelonephritis. The same percentage of cases (12%) were chronic obstructive pulmonary disease and iron deficiency anemia, 11%

MODERN PRINCIPLES FOR LOCAL MANAGEMENT OF PURULENT WOUNDS

At present, surgical infection is one of the most thorny, difficult and urgent issues in clinical practice and is a great social and ecological importance globally. Growing number of suppurative and necrotizing lesions, postoperative suppurative complications, cases of generalized infection and various toxic and allergic reactions are among the challenges the surgeons have to encounter in daily practice. Patients with suppurative inflammatory lesions, which occurrence rate is reaching out 35 – 40% of soft tissue inflammatory cases, constitute a considerable share of all surgical patients. And sometimes the treatment outcomes of such conditions are unsatisfactory. Under the body immune response, the number of postoperative suppurative complications is demonstrates a tendency toward the growth. The clinical course of such suppurative processes is usually acute and often causes systemic infection, sepsis, and even lethal outcomes. In the total number of the lethal cases in surgical inpatient departments, the number of acute surgical infection ranges from 40 to 60%. Moreover, there has been an increase in a number of chronic cases resulted from acute ones that require more time and expenses to manage them. Long hospital staying, insufficient treatment efficacy of existing techniques, considerable economic losses for rehabilitation evidence the range of questions unsolved. The literary review has shown that early detection and proper management of purulent foci is among the leading factors of successful management of surgical wounds. Despite the active implementation of new approaches and techniques for the treatment of purulent wounds, so called "under the bandage" wound management is of considerable clinical importance, therefore the right selection of wound dressing materials, different by their chemical nature, dressings techniques, medications is one of the most promising ways on local treatment of suppurative wounds that can significantly increase the effectiveness of the treatment outcomes.

Опыт применения тоцилизумаба у стационарных пациентов со среднетяжелым течением COVID-19

Severe form of COVID 19 has been linked to the phenomenon of dysregulated inflammation with excessive cytokine release and elevated interleukin 6 (IL6) levels. Suppressive agents enabling specific inhibition of cytokines, notably monoclonal antibodies to IL6 and its receptors, have been applied as a rescue therapy in COVID 19 despite the underexplored clinical scope for these biologic medications. This study aimed to evaluate the clinical utility of IL6 receptor antagonist tocilizumab in moderate symptomatic COVID 19 prone to aggravation. The retrospective cohort study enrolled two groups of hospitalized patients (a total of n = 72) diagnosed with moderate COVID-19. The main group received a single 400 mg dose of tocilizumab (TCZ) on top of standard therapy. The comparative analysis included statistical evaluation for a number of clinical and laboratory parameters at reference time points and disease outcomes with regard to treatment strategy. Overall, TCZ administration provided no advantages in terms of oxygen supplementation status, disease progression, or survival. Lethal cases constituted 19.2% (10 pts) and 5% (1 pt) in TCZ and comparison groups, respectively. The results indicate that administration of monoclonal antibody drugs in hospital patients with COVID-19 must follow differential schemes with regard to the disease severity and comorbidities, as well as proper commencement schedules.

Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients

BackgroundSARS-CoV-2 infection portends a broad range of outcomes, from a majority of asymptomatic cases to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty, and co-morbidities such as obesity, diabetes, and cardiovascular disease. A precise knowledge of the molecular and biological mechanisms that may explain the association of severe disease with male sex is still lacking. Here, we analyzed the relationship of serum testosterone levels and the immune cell skewing with disease severity in male COVID-19 patients.MethodsBiochemical and hematological parameters of admission samples in 497 hospitalized male and female COVID-19 patients, analyzed for associations with outcome and sex. Longitudinal (in-hospital course) analyses of a subcohort of 114 male patients were analyzed for associations with outcome. Longitudinal analyses of immune populations by flow cytometry in 24 male patients were studied for associations with outcome.ResultsWe have found quantitative differences in biochemical predictors of disease outcome in male vs. female patients. Longitudinal analyses in a subcohort of male COVID-19 patients identified serum testosterone trajectories as the strongest predictor of survival (AUC of ROC = 92.8%, p < 0.0001) in these patients among all biochemical parameters studied, including single-point admission serum testosterone values. In lethal cases, longitudinal determinations of serum luteinizing hormone (LH) and androstenedione levels did not follow physiological feedback patterns. Failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and augmented circulating classical monocytes.ConclusionsRecovery or failure to reinstate testosterone levels is strongly associated with survival or death, respectively, from COVID-19 in male patients. Our data suggest an early inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by full recovery in survivors or a peripheral failure in lethal cases. These observations are suggestive of a significant role of testosterone status in the immune responses to COVID-19 and warrant future experimental explorations of mechanistic relationships between testosterone status and SARS-CoV-2 infection outcomes, with potential prophylactic or therapeutic implications.

Availability of specialized medical care in cases of severe head injuries during the COVID-19 pandemic

Background: The pandemic of COVID-19 caused an overload of national health care systems worldwide. The analyses of the ways the pandemic changed the availability of the medical care provided in emergency situations has been carried out based on cases of craniocerebral trauma treatment.Material and methods: Data for the period of 2019–2020 on each of 85 territorial subjects of the Russian Federation which are contained in forms of the state statistical observation and also data of Federal State Statistics Service on number of the deceased from head injuries (bone fractures of skull and face) in the period of 2019–2020 have been analyzed. For the measurement of medical care availability level we used the ratio of number of hospitalizations to the total number of deaths due to head injury in territorial subjects of the Russian Federation before COVID-19 pandemic (in 2019) and during the pandemic in 2020. The higher the ratio of admissions in the round-the-clock hospitals to total number of lethal cases due to head trauma, the higher the availability of the specialized emergency medical care. At the same time, we recognize that if the person with a severe head injury is brought to the hospital alive the chances to save his life increase.Results: In 2019 approximately half of the patients with cases of head injuries were admitted in the round-the-clock hospital (the ratio is 274.6 thousand cases of hospitalization to 566.6 thousand cases of the head injury – 48.5% of the total number of head injury cases). In 2020 the share of such cases decreased to 43.1% – 207.5 thousand cases of hospitalization to 481.3 thousand cases of head injury in a year total. On an average in territorial subjects of the Russian Federation the ratio coefficient of hospitalizations number to the total number of lethal outcomes due to head injury in 2019 was 11.6 ± 4.3, in 2020 – 8.8 ± 3.3. Feature variation coefficient is 37.5% and 37.6% in 2019 and 2020 respectively which demonstrates its high variability in territorial subjects of the Russian Federation. A share of the lethal outcomes due to a head injury increased from 3.8% in 2019 to 4.5% in 2020 of total number of patients that received this type of trauma, or by 1.2 times.Conclusion: Due to the decrease of the emergency specialized medical care availability because of the pandemic the excess mortality from severe head injuries in 2020 was not less than 3 thousand people or 15% of the total number of cases of death. Hospital repurposing, redistribution of temporary and physical healthcare resources during the pandemic shouldn’t be followed by the decrease of medical care in emergency cases. The relation indicator of the number of admissions in the round-the-clock hospitals of patients with severe injuries or diseases to total number of lethal outcomes due to the same reasons is the indicator showing the availability level of medical care that can’t be delayed.

Modified vaccinia Ankara expressing EEHV1A glycoprotein B elicits humoral and cell-mediated immune responses in mice.

Elephant endotheliotropic herpesvirus (EEHV) can cause lethal hemorrhagic disease (EEHV-HD) in Asian elephants and is the largest cause of death in captive juvenile Asian elephants in North America and Europe. EEHV-HD also has been documented in captive and wild elephants in their natural range countries. A safe and effective vaccine to prevent lethal EEHV infection would significantly improve conservation efforts for this endangered species. Recent studies from our laboratory suggest that EEHV morbidity and mortality are often associated with primary infection. Therefore, we aim to generate a vaccine, particularly for EEHV1 naïve animals, with the goal of preventing lethal EEHV-HD. To address this goal, we generated a Modified Vaccinia Ankara (MVA) recombinant virus expressing a truncated form of glycoprotein B (gBΔfur731) from EEHV1A, the strain associated with the majority of lethal EEHV cases. Vaccination of CD-1 mice with this recombinant virus induced robust antibody and polyfunctional T cell responses significantly above mice inoculated with wild-type MVA. Although the vaccine-induced T cell response was mainly observed in CD8+ T cell populations, the CD4+ T cell response was also polyfunctional. No adverse responses to vaccination were observed. Overall, our data demonstrates that MVA-gBΔfur731 stimulates robust humoral and cell-mediated responses, supporting its potential translation for use in elephants.

Looking for a Simplified Diagnostic Model to Identify Potentially Lethal Cases of Prostate Cancer at Initial Diagnosis: An ImGO Pilot Study.

Simple SummarySeveral genetic anomalies are recurrent in prostate cancer (PC) and allow this disease to be classified into distinct molecular subtypes; however, these anomalies have no predictive role and have limited relevance for clinical practice. Within this pilot study, metastatic castration-resistant PC (mCRPC) and metastatic castration-sensitive PC (mCSPC) were used for identifying and understanding lethal prostate tumor clones, from a genomic point of view. Some elements, such as a high Gleason Score and the presence of a cribriform pattern or intraductal carcinoma were evaluated as phenotypic markers of potentially lethal PC. Our results provide hypothesis-generating data, as the idea of evaluating mCSPC and mCRPC as a phenotypic/biologic model able to be translated in clinical practice. The confirmation of a high incidence of TP53 and BRCA2 mutations in larger trials may find a therapeutic implication through the choice of whether or not to use “more” therapy in respect to “selective” treatments approaches.The recurrent genetic anomalies used to classify prostate cancer (PC) into distinct molecular subtypes have limited relevance for clinical practice. In consideration of WHO 2016 histological classification, which includes the introduction of Gleason Score 4 for patients with cribriform component and the definition of intraductal carcinoma as a new entity, a retrospective pilot study was conducted to investigate, by histological review, if there were any variations of Gleason Score and the incidence of intraductal carcinoma and cribriform pattern, intended as “phenotypic” markers of potentially lethal PC, among metastatic castration-sensitive PC (mCSPC) and metastatic castration-resistant PC (mCRPC) samples. Potentially predictive factors were also assessed. Among 125 cases, a variation in the Gleason Score was reported in 26% of cases. A cribriform (36%) or intraductal (2%) pattern was reported in a higher percentage. Of them, a primary Gleason pattern 4 was reported in 80% of cases. All patients with intraductal carcinoma present a BRCA2 mutation, also found in 80% of cases with a cribriform pattern. This pilot study documented some hypothesis-generating data, as the evaluation of de novo mCSPC and mCRPC as phenotypic/biologic model to be translated in clinical practice. A cribriform pattern/intraductal carcinoma might be a marker of potentially lethal PC. The high incidence of TP53 and BRCA2 mutations in de novo mCSPC may also have a therapeutic implication.

A Lethal Case of Natural Infection with the H5N8 Highly Pathogenic Avian Influenza Virus of Clade 2.3.4.4 in a Mandarin Duck

Recent global outbreaks of highly pathogenic avian influenza viruses (HPAIVs) of the H5N8 subtype in poultry and wild birds have raised concerns about animal and human health, particularly after its first evidence of zoonotic transmission from birds to humans. Here, we report a lethal infection with the H5N8 HPAIV in a mandarin duck that had previously demonstrated resistance to the H5N8 HPAIV infection. In addition, we revealed that the isolated virus was a genetic reassortant between the existing H5N8 HPAIV and LPAIV(s). Although further studies are warranted to assess the impact of the genetic reassortment on virus pathogenicity, the potential role of mandarin ducks in HPAIV dissemination should be re-evaluated.

Spontaneous pneumomediastinum, pneumothorax, pneumoperitoneum and soft tissue emphysema as complication in patients with COVID-19, series of cases

Spontaneous pneumomediastinum, pneumothorax, pneumoperitoneum, and soft tissue emphysema have been recently described in several sources as possible complications in patients with severe COVID-19 and lung damage. This clinical case is dedicated to demonstrarte the development of these lesions in 3 male patients with comorbid conditions. The putative pathophysiological mechanism of these complications is air leakage due to extensive diffuse alveolar damage followed by rupture of the alveoli. All presented patients had a favorable outcome of the disease without lethal cases, their laboratory data and clinical dynamics were described.It should be noted that such conditions are not rare complications of COVID-19, and are observed mainly in male patients with severe form of the disease and the presence of comorbid conditions. Such complications are associated with long hospitalization and a severe prognosis. In some cases, with a mild course of the disease and positive dynamics in a decrease of the percentage of pulmonary lesions, the outcome is favorable, not requiring additional invasive interventions.

Urinary 6-sulfatoxymelatonin Levels and Prostate Cancer Risk among Men in the Multiethnic Cohort.

The circadian hormone melatonin has anticancer properties, and prior studies suggest a positive association between low melatonin and prostate cancer risk. The purpose of this study was to examine urinary melatonin levels and prostate cancer in a racially/ethnically diverse cohort. We conducted a nested case-control study, including 1,263 prostate cancer cases and 2,346 controls, sampled from participants in the Multiethnic Cohort Study with prediagnostic urine samples assayed for 6-sulfatoxymelatonin, the primary melatonin metabolite. Conditional logistic regression was used to examine the association between melatonin levels and the development of prostate cancer outcomes (all incident cases, advanced, lethal, high-grade, and aggressive), overall and by race/ethnicity. Among 1,263 cases, 135 were advanced stage, 101 were lethal cases, and 282 were high-grade disease. Median melatonin levels were similar in controls [17.12 ng/mL; interquartile range (IQR), 19.78] and cases (17.93 ng/mL; IQR, 19.76), and we found no significant association between urinary melatonin levels and prostate cancer risk overall or in any clinical or racial subgroup. In this diverse cohort, there was no significant association between melatonin and any prostate cancer outcome, nor were there any differences by racial/ethnic group. These results do not support a strong association between melatonin levels and risk of prostate cancer.

Adipose tissue in COVID-19: detection of SARS-CoV-2 in adipocytes and activation of the interferon-alpha response

ObjectiveObesity is a recognized risk factor for the progression to severe forms of COVID-19, yet the mechanisms of the association are unclear.MethodsSubcutaneous abdominal adipose tissue specimens of subjects deceased from COVID-19 (n = 23) were compared to those of controls dying abruptly from causes other than infectious (accidental trauma, sudden cardiac death). Alterations of lung parenchyma consistent with moderate to severe disease were detected in all COVID-19 cases, not in controls. Investigations included: histopathologic features, detection of virus antigens and genome, characterization of infiltrating leukocytes, transcription levels of immune-related genes.ResultsBy RT-PCR, the SARS-CoV-2 genome was detected in the adipose tissue of 13/23 (56%) cases of the COVID-19 cohort. The virus nucleocapsid antigen was detected in the cytoplasm of 1–5% adipocytes in 12/12 COVID-19 cases that were virus-positive by PCR in the adipose tissue (one case could not be assessed due insufficient tissue). The adipose tissue of COVID-19 cases showed leukocyte infiltrates and upregulation of the interferon-alpha pathway. After adjusting for age and sex, the activation score of IFN-alpha was directly related with transcription levels of the ACE2 gene, a key entry factor of SARS-CoV-2.ConclusionsIn lethal COVID-19 cases, the SARS-CoV-2 nucleocapsid antigen has been detected in a sizeable proportion of adipocytes, showing that the virus may directly infect the parenchymal cells of subcutaneous fat. Infection appears to activate the IFN alpha pathway and to attract infiltrating leukocytes. Due to the huge numbers of adipocytes in adults, the adipose tissue represents a significant reservoir for SARS-CoV-2 and an important source of inflammatory mediators.

Spontaneous pneumomediastinum, pneumothorax, pneumoperitoneum and soft tissue emphysema as complication in patients with COVID-19, series of cases

Spontaneous pneumomediastinum, pneumothorax, pneumoperitoneum, and soft tissue emphysema have been recently described in several sources as possible complications in patients with severe COVID-19 and lung damage. This clinical case is dedicated to demonstrarte the development of these lesions in 3 male patients with comorbid conditions. The putative pathophysiological mechanism of these complications is air leakage due to extensive diffuse alveolar damage followed by rupture of the alveoli. All presented patients had a favorable outcome of the disease without lethal cases, their laboratory data and clinical dynamics were described.It should be noted that such conditions are not rare complications of COVID-19, and are observed mainly in male patients with severe form of the disease and the presence of comorbid conditions. Such complications are associated with long hospitalization and a severe prognosis. In some cases, with a mild course of the disease and positive dynamics in a decrease of the percentage of pulmonary lesions, the outcome is favorable, not requiring additional invasive interventions.

Clinical Application of Tocilizumab in Covid-19 Patients

Over these previous years, clinicians dealing with patients with COVID infection 2019 have discovered that the abundant inflammatory response induced by the virus serves as a significant cause of the acute respiratory distress syndrome (ARDS) and multi-organ dysfunction, which happen in majority of the lethal cases. Presently, there is not a single drug available as an approved and genuine medication for corona infection, in this sphere of time immunomodulatory agents has exhibited encouraging response against coronavirus infection. The initial finding that interleukin-6 (IL-6) levels are raised in serious COVID-19 and independently foresee the risk of developing ARDS and finally death, such results had centered the clinical investigations on this pro-incendiary and pleiotropic cytokine. Tocilizumab (TCZ) is humanized anti-interleukin 6 receptor monoclonal immunizer and has been endorsed for different rheumatological ailments. Currently, many steroids as they act as an immunomodulatory agent have shown fantastic therapeutic effects while used in COVID infected peoples, such clinical data advocated the application of tocilizumab to combat corona infection. Patients who were in life threatening condition because of COVID-19 initiated pneumonia developed hyper aggravation. This medication lessens the further decay of the patient caused because of agglomeration of lymphocytic cells and diminishes the degree of high CRP (C-responsive protein). Nevertheless, several clinical investigations have been in progress to ascertain the drug profile. So that TCZ may be used in COVID patients with optimal effectiveness associated with minimum risk of adverse events. In this article, we have tried to encompass all relevant information about the pharmacology of TCZ, which will surely help to understand clinical behaviour of the drug.

Surgical treatment for cystic lesions of the pancreas

During the period 2011–2021, 45 patients with pancreatic cysts were treated at the AlexanderMariinsky Regional Clinical Hospital in Astrakhan. All patients were divided into 2 groups. 20 patients of the first group (45%) underwent external drainage of cysts, 7 out of them underwent obliteration of residual cavities by the method developed by us. To do this, the drug Povidone – Iodine 10% was used. The second group included 25 (55%) patients with internal drainage of cysts: in 5 patients (11%) pancreacystogastrostomy was performed; in 9 patients (20%) — pancreatocystoejunostomy; in 5 patients (11%) — pancreatic drainage; in 5 (11%) — laparoscopic cystectomy; and open echinococcectomy was performed in 1 patient (2%). Clinical, laboratory, instrumental and statistical research methods were carried out. A comparative evaluation of two methods of drainage operations for pancreatic cysts showed the advantage of internal drainage over external. 7 (16%) patients had a variety of complications. The recurrence of cysts was 4 (9%) cases. All the patients recovered. There were no cases of lethality.

ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ МИНИИНВАЗИВНОЙ ЭПИКАРДИАЛЬНОЙ ВИДЕОАССИСТИРОВАННОЙ РАДИОЧАСТОТНОЙ ИЗОЛЯЦИИ ЛЕГОЧНЫХ ВЕН ПРИ ИЗОЛИРОВАННОЙ ФИБРИЛЛЯЦИИ ПРЕДСЕРДИЙ

Aim. To analyze long-term results of the use of minimally invasive epicardial video-assisted radiofrequency ablation (RFA) of the pulmonary veins (PV) in patients with various forms of isolated atrial fibrillation (AF). Materials and methods. Since February 2011 to December 2014, 22 patients (male/female – 21/1) with paroxysmal / persistent / long-standing persistent idiopathic form of AF were operated on the basis of the Republican Scientific and Practical Center “Cardiology”, 7 (31.8%) / 9 (41%) / 6 (27.2%) cases respectively. Mean age was 48.33 ± 9.37 (31–66) years old. The average duration of the history of AF before the operation was 58.6 ± 32.5 months. RFA was performed through a bilateral mini-thoracotomy approach using video endoscopy with the application of bipolar irrigated Gemini X ablative clamp electrodes. All patients underwent bilateral antral RFA isolation of the PVs. In 100% of patients it was possible to achieve a conduction block from the PV collectors. Results. During the hospital period, there were not no lethal cases, conversions to sternotomy, and neurological complications. The long-term period was studied in 100% of patients, the average follow-up period was 7.4+0.5 years. The final rhythm was assessed using Holter monitoring in 3, 6, and 12 months after surgery, then annually. In 6 (28%) cases in patients with initial non-paroxysmal AF, endocardial RFA of the isthmus of the right atrium or PV orifices was performed at different times after surgery due to the presence of atrial flutter (4/19%) or AF (2/9.5%). Implantation of the pacemaker was required in 2 cases (9.0%). The ef fectiveness of bipolar antral RFA isolation of the PV using the Gemini X device, depending on the initial form of AF in the long-term period: paroxysmal – 100%, persistent – 66.7%, long-term persistent – 33.3%. Conclusion. Epicardial minimally invasive bipolar antral PV isolation is a highly effective treatment for paroxysmal AF. In non-paroxysmal forms of AF, it is necessary to expand isolation of arrhythmogenic zones in the atria.