Severe Infectious Complications Research Articles

Tannic acid and silicate functionalized polyvinyl alcohol-hyaluronic acid hydrogel for infected diabetic wound healing

Abstract Healing of chronic diabetic wound is challenging due to complications of severe inflammatory microenvironment, bacterial infection and poor vascular formation. Herein, a novel injectable polyvinyl alcohol (PVA)-hyaluronic acid (HA) based composite hydrogel was developed, with TA and silicate functionalization to fabricate a “all-in-one” hydrogel PTKH. On one hand, after local injection to wound site the hydrogel underwent a gradual sol-gel transition in situ to form adhesive and protective dressing for the wound. Manipulations of rheological characteristic, mechanical properties and swelling ability of PTKH could be performed via regulating tannic acid and silicate content in hydrogel. On the other hand, PTKH was capable of eliminating ROS overexpression, combating infection and generating a cell-favored microenvironment for wound healing acceleration in vitro. Subsequent animal studies demonstrated that PTKH could greatly stimulate angiogenesis and epithelization, accompanied with inflammation and infection risk reduction. Therefore, in consideration of its impressive in vitro and in vivo outcomes, this “all-in-one” multifunctional hydrogel may hold promise for chronic diabetic wound treatment.

Targeted rescue of synaptic plasticity improves cognitive decline in sepsis-associated encephalopathy

Sepsis-associated encephalopathy (SAE) is a frequent complication of severe systemic infection resulting in delirium, premature death, and long-term cognitive impairment. We closely mimicked SAE in a murine peritoneal contamination and infection (PCI) model. We found long-lasting synaptic pathology in the hippocampus including defective long-term synaptic plasticity, reduction of mature neuronal dendritic spines, and severely affected excitatory neurotransmission. Genes related to synaptic signaling, including the gene for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and members of the transcription-regulatory EGR gene family, were downregulated. At the protein level, ARC expression and mitogen-activated protein kinase signaling in the brain were affected. For targeted rescue we used adeno-associated virus-mediated overexpression of ARC in the hippocampus invivo. This recovered defective synaptic plasticity and improved memory dysfunction. Using the enriched environment paradigm as a non-invasive rescue intervention, we found improvement of defective long-term potentiation, memory, and anxiety. The beneficial effects of an enriched environment were accompanied by an increase in brain-derived neurotrophic factor (BDNF) and ARC expression in the hippocampus, suggesting that activation of the BDNF-TrkB pathway leads to restoration of the PCI-induced reduction of ARC. Collectively, our findings identify synaptic pathomechanisms underlying SAE and provide a conceptual approach to target SAE-induced synaptic dysfunction with potential therapeutic applications to patients with SAE.

Should we review our prophylaxis approach for increased antibiotic resistance in transrectal prostate biopsy?

This study aims to show the bacteriologic picture of acute prostatitis and bacteremia caused by infective agent after transrectal ultrasound-guided prostate biopsy (TRUSBx) and to determine the resistance rates of the infections in patients undergoing transrectal biopsy and to guide prophylaxis approach before biopsy. The retrospective data of 935 patients who underwent TRUSBx between January 2010 to January 2019 were reviewed. Pre-biopsy urine cultures and antimicrobial susceptibility were obtained. Subsequently, patients admitted to the hospital with any complaint after biopsy were examined for severe infection complications. Of the 430 (61.7%) patients who underwent urine culture before the procedure, 45 (10.5%) had growth; 30 (66.7%) of the growing microorganisms were Escherichia coli. Twenty (44.4%) of all Gram-negative agents in pre-biopsy urine culture were susceptible to quinolone. Post TRUSBx bacteremia was present in 18.2%, urinary system infection in 83.6%, and hospitalization in 61.8% of 55 patients who were admitted to the hospital. In the isolated gram-negative microorganisms, fluoroquinolones resistance in urinary system infections was seen in 40% and bacteremia was seen in 70% of the cases. ESBL-producing Gram-negative bacteria were determined in 40% of infections in blood and 38.5% of urinary system infections in the post biopsy period in the current study. These high antibiotic resistance rates suggest that we better review our pre-procedure prophylaxis approaches.

The association between renal pelvis urine density and the risk of severe infectious complications in patient with symptom-free hydronephrosis after shock wave lithotripsy: a multi-center prospective study.

Finding reliable and easy-to-obtain predictors of severe infectious complications after shock wave lithotripsy (SWL) is a major clinical need, particular in symptom-free hydronephrosis. Therefore, we aim to prospectively investigate the predictive value of Hounsfield units (HU) in renal pelvis urine for the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL. This multi-center prospective study was conducted from June 2020 to December 2023. The HU of renal pelvis urine was measured by non-enhanced computed tomography. The severe infectious complications included systemic inflammatory response syndrome, sepsis, and septic shock. Binary logistic regression models assessed the odds ratios (ORs) and 95% confidence intervals (CIs). Finally, 1,436 patients with ureteral stones were enrolled in this study. 8.9% (128/1,436) of patients experienced severe infectious complications after SWL treatment. After adjusting confounding variables, compared with the patients in the lowest renal pelvis urine density quartile, the OR (95% CI) for the highest quartile was 32.36 (13.32, 78.60). There was a positive linear association between the HU value of renal pelvis urine and the risk of severe infectious complications after SWL (P for trend < 0.001). Furthermore, this association was also observed stratified by age, gender, BMI, stone size, stone location and hydronephrosis grade (all P for interaction > 0.05). Additionally, the nonlinear association employed by restricted cubic splines is not statistically significant (nonlinear P = 0.256). The AUROC and 95%CI of renal pelvis urine density were 0.895 (0.862 to 0.927, P value < 0.001). The cut-off value was 12.0 HU with 78.59% sensitivity and 85.94% specificity. This multi-center prospective study demonstrated a positive linear association between HU in renal pelvis urine and the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL, regardless of age, gender, BMI, stone size, stone location, and hydronephrosis grade. These findings might be helpful in the SWL treatment decision-making process.

Patients with aggressive B-cell lymphoma receiving CAR T-cell therapy have a low rate of severe infections despite lack of universal antibacterial and antifungal prophylaxis.

Our aim was to describe the frequency and severity of infectious complications after chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL). We retrospectively reviewed clinical records of LBCL patients treated with CD19-targeted CAR T-cell therapy from July/2018 to December/2021 at our institution, and identified all infectious episodes from CAR T-cell infusion until disease progression, death or last follow-up. Overall, 137 patients were included. Thirty six percent had received ≥3 previous lines of therapy and 26% an autologous hematopoietic cell transplantation (auto-HCT). Cytokine release syndrome occurred in 87 (64%) patients. Antibacterial prophylaxis was not used in any patient; only 38% received antifungal prophylaxis. Sixty three infectious events were observed in 41 (30%) patients. Fifty two (83%) of the infectious events had at least one pathogen identified (bacteria [n = 38], virus [n = 11], and fungi [n = 3]). Most of the infectious events occurred during hospitalization for CAR-T treatment. Infection-related mortality was observed in two patients. Independent risk factors for infection included male gender, previous auto-HCT, ≥3 lines of treatment and pre-lymphodepletion neutropenia. Infections after CAR T-cell therapy in patients with lymphoma are frequent but generally not severe. A conservative and tailored antimicrobial prophylaxis seems to be a safe approach.

An Emerging Threat: A Systematic Review of Endocarditis Caused by Gemella Species.

Infective endocarditis caused by Gemella species is increasingly recognized as an emerging clinical entity. Gemella species are fastidious gram-positive cocci that are typically commensal organisms but can become opportunistic pathogens. This systematic review aimed to provide a comprehensive overview of endocarditis due toGemellaspecies by synthesizing existing evidence. A total of 52 case reports were identified through a rigorous search and selection process. The most prevalent causative species were G. morbillorum (46.3%) and G. haemolysans (25.9%), with a striking male predominance (79.6%). The clinical presentation was largely nonspecific, mirroring typical infective endocarditis. However, the indolent nature of the illness and fastidious growth requirements of Gemella species often led to diagnostic delays. Echocardiography, particularly transesophageal echocardiography, played a crucial role in the diagnosis, enabling the detection of valvular vegetation and the assessment of complications. Management posed significant challenges, including the need for broad-spectrum empirical antibiotic therapy and increasing antimicrobial resistance among Gemella isolates. Surgical intervention was frequently required for severe valvular dysfunction, persistent infection, or embolic complications. Despite advances in diagnosis and treatment, endocarditis due toGemellaspeciesremains associated with significant morbidity and mortality, underscoring the importance of early recognition and multidisciplinary management. This review highlights the emerging clinical significance of Gemella species as causative agents of infective endocarditis and identifies areas for further research.

Disseminated HIV-associated venous thrombosis (a case report)

Introduction. In 1983, Robert Gallo (USA) and Luc Montagnier (France) discovered the human immunodeficiency virus (HIV). Today, about 39 million people are living with HIV worldwide. Thanks to antiretroviral therapy (ART), HIV has become a manageable chronic condition for most patients. However, the number of associated complications, including cardiovascular disease and thrombosis, is increasing. HIV-associated venous thrombosis, such as deep vein thrombosis and pulmonary embolism, requires attention and research due to their serious consequences.&#x0D; The purpose was to summarize, analyze, and demonstrate the clinical sequence, diagnostic difficulties and treatment of a rare case of disseminated venous thrombosis in the setting of HIV infection.&#x0D; Materials and methods. Periodical medical publications, patient records, and materials of scientific and practical conferences were used. Research methods: historical, bibliographic, systematic approach, analytical, generalization.&#x0D; Results. The article analyses in detail the data on a severe complication of HIV infection - disseminated venous thrombosis. To establish the final diagnosis, differential diagnosis with infectious, rheumatological, and myeloproliferative diseases was performed. As a result of the differential diagnosis, a multidisciplinary team of doctors established homozygous carriage of the MTHFR 1298 gene, which determines an increased risk of thrombosis. The addition of HIV infection could be a trigger for the development of severe thrombosis with impaired internal organ function. &#x0D; Conclusions. All countries of the world continue to face the problem of HIV infection, which requires constant detection among the population, including military personnel. In the case of thrombosis under consideration, both HIV infection itself (reduced CD4 T-cell counts, late HIV detection) and genetic factors could be the cause. The patient's multidisciplinary management proved to be effective, which allowed him to achieve a positive result, and his fight against the disease will continue.

Caspase-8 activation regulates enterovirus D68 infection-induced inflammatory response and cell death

Enterovirus D68 (EV-D68) infection causes severe acute respiratory infection and severe neurological complications, such as acute flaccid myelitis (AFM), in children. However, although EV-D68 has pandemic potential, no effective drugs or vaccines are currently clinically available. Furthermore, EV-D68 infection-induced inflammatory response and cell death are not fully understood. In this study, we demonstrated that several inflammatory cytokines were upregulated in a multiplicity of infection (MOI) dependent manner in EV-D68-infected human rhabdomyosarcoma (RD) cells. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed that tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand-5 (CCL-5), and CXC motif chemokine ligand-5 (CXCL-5) mRNA levels were highly upregulated after EV-D68 infection. IL-1β processing and maturation mediated by caspase-8 was inhibited by the caspase-8 inhibitor Z-IETD-FMK. EV-D68 infection activates caspase-8 to mediate IL-1β maturation and secretion. Additionally, EV-D68 activated cell death-related proteins such as caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1), phosphorylation of Mixed Lineage Kinase domain-like protein (pMLKL), and gasdermin E (GSDME). Thus, EV-D68 infection activates caspase-8, which triggers the necroptosis and apoptosis pathways. Overall, our data suggest that caspase-8 activation is associated with the inflammatory response and cell death in EV-D68-infected RD cells. This mechanism represents a novel target for the treatment of EV-D68 infection by inhibiting caspase-8 activation.

Periprosthetic Joint Infection as a Socio-Economic Problem of Modern Orthopedics

Periprosthetic joint infection is the main social and economic problem of modern orthopedics with a recurrence rate of chronic forms of up to 23.2–31.5%. The aim of this review is to inform various specialties doctors about the features of pathogenesis, etiology and treatment of periprosthetic joint infection, which significantly differ it from of other surgical site infections. The severity of infectious complications is due to the suppression of the patient’s immune system and microbial biofilms. Surgical treatment of periprosthetic joint infection involves debridement with preservation or removal of the implants, resection arthroplasty and arthrodesis. Today, in the treatment of more than 80% of cases of chronic infection, a two-stage approach is used, which allows to restore joint function after an average of 1.0–1.5 years. An integral part of the treatment of patients is high-dose, long-term and combined antibiotic therapy, which allows you to effectively deal with the leading pathogens of periprosthetic infection Staphylococcus aureus and S. epidermidis, the share of which is 46.5–57.5%. In the conditions of growing resistance of bacteria to antibiotics, the interest of researchers in the possibilities of using bacteriophages in the complex therapy of infections of bones and joints has increased. The cost of treatment exceeds the cost of “aseptic” joint replacement by 2–24 times and is characterized by a high level of disability and mortality of patients. Taking into account the numerous factors affecting the course and effectiveness of complex treatment of patients with periprosthetic infection, a multidisciplinary approach is currently considered the main component of success. The medical and social significance and high financial costs of treating patients with periprosthetic infection indicate the need for further research and the active implementation of effective scientific developments in the practical healthcare system.

RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway.

Hepatic ischemia-reperfusion injury (HIRI) is a prevalent complication of liver transplantation, partial hepatectomy, and severe infection, necessitating the development of more effective clinical strategies. Receptor activity-modifying protein 1 (RAMP1), a member of the G protein-coupled receptor adapter family, has been implicated in numerous physiological and pathological processes. The study aimed to investigate the pathogenesis of RAMP1 in HIRI. We established a 70% liver ischemia-reperfusion model in RAMP1 knockout (KO) and wild-type mice. Liver and blood samples were collected after 0, 6, and 24 h of hypoxia/reperfusion. Liver histological and serological analyses were performed to evaluate liver damage. We also conducted in-vitro and in-vivo experiments to explore the molecular mechanism underlying RAMP1 function. Liver injury was exacerbated in RAMP1-KO mice compared with the sham group, as evidenced by increased cell death and elevated serum transaminase and inflammation levels. HIRI was promoted in RAMP1-KO mice via the induction of hepatocyte apoptosis and inhibition of proliferation. The absence of RAMP1 led to increased activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and yes-associated protein (YAP) phosphorylation, ultimately promoting apoptosis. SCH772984, an ERK/MAPK phosphorylation inhibitor, and PY-60, a YAP phosphorylation inhibitor, reduced apoptosis in in-vitro and in-vivo experiments. Our findings suggest that RAMP1 protects against HIRI by inhibiting ERK and YAP phosphorylation signal transduction, highlighting its potential as a therapeutic target for HIRI and providing a new avenue for intervention.

Valsalva Manoeuvre-Induced Pneumothorax and Pneumomediastinum in a Covid-19 Patient with ARDS: An Unusual Mechanism for this Complication.

Until now, only a few cases of Valsalva-induced barotraumas (pneumothorax, pneumomediastinum and subcutaneous emphysema) have been described, and none of them among COVID-19 patients. A man in his 50s was admitted for SARS-CoV-2-related acute respiratory distress syndrome (ARDS). Initial evolution was favourable with non-invasive ventilatory support, high-flow oxygen nasal cannula and the best supportive drugs available at the time. During the Valsalva manoeuvre while defecating, the patient reported sudden chest pain and showed a new acute hypoxemic respiratory failure due to a pneumothorax. It led to multiple complications (pulmonary embolism, haemoptysis, and cardiac arrest), and despite the best supportive care, led to the patient's death. The Valsalva manoeuvre can be an overlooked cause of pneumothorax in patients with COVID-19. Predisposition to barotrauma in COVID-19 patients could be explained by several factors, including the extensive use of non-invasive and invasive ventilation during the pandemic, and the histological changes observed in the lungs of those infected with COVID-19. We report the first description of a Valsalva-induced barotrauma in a COVID-19 infection. We emphasise the importance of treating constipation particularly in severe COVID-19 cases, to prevent complications such as barotrauma. Pneumothorax is a common complication of severe COVID-19 infection, but Valsalva manoeuvre-induced pneumothorax in COVID-19 patients has never been reported previously.Particular care should be taken to prevent and treat constipation in hospitalised patients as it may cause a wide range of complications, including barotraumatism.The extensive use of non-invasive and invasive ventilation may play a role in barotrauma, but causal association has not been proven.

Динамика выявления РНК вируса SARS-CoV-2 у пациентов и сотрудников ФГБУ «НМИЦ гематологии» Минздрава России в первые 2 года пандемии новой коронавирусной инфекции COVID-19

Background. COVID-19 required fundamental changes in healthcare management, also in medical care for oncological and hematological patients. Visits to healthcare organizations were minimized, 75 % of doctor appointments were converted to telemedicine consultations. The solutions aimed at preventing further spread of COVID-19 included establishing of observational units, distinguishing between patient and employee flows, regular SARS-CoV-2 RNA testing, reducing hospital stays and transferring patients with positive COVID-19 tests to the remodeled hospitals specializing in the novel coronavirus infection, as well as providing only emergency medical treatment and, as far as feasible, converting systemic chemotherapy to per os treatment, etc.&#x0D; Aim. To assess SARS-CoV-2 RNA detection dynamics at the National Research Center for Hematology from April 2020 to January 2022 during the implementation of epidemic control measures.&#x0D; Materials &amp; Methods. The study was based on SARS-CoV-2 RNA testing of naso- and oropharyngeal samples obtained from patients and employees of the National Research Center for Hematology (hereafter referred to as Center). Besides, bronchoalveolar lavage fluid, lung tissue biopsies, and sputum were examined for SARS-CoV-2 RNA. The study was performed at the Center’s Virusology Department with the use of Sintol reagent kit “ПЦР-РВ-2019-nCov”.&#x0D; Results. The study was based on 107,470 tests: 58,141 (54 %) of employees and 45,126 (46 %) of patients; 35,508 (33 %) of men and 71,962 (67 %) of women. In 1318 cases SARS-CoV-2 RNA was detected which accounted for 1.15 % of total test number. In the groups of employees/patients, virus detection rate was 1.42 %/1.09 % (p &lt; 0.001), and in male/female groups it was 1.3 %/1.2 %, respectively (p = 0.154). The rate of infection in the groups of tumor and non-tumor hematological patients, as proved by SARS-CoV-2 RNA testing, was 1.24 % and 0.92 %, respectively (p = 0.147). In employees and patients of the Center, a wave-like virus detection rate was observed. The largest number of infections was registered in April-June 2020 (79 patients and 170 employees), October-December 2020 (126 patients and 190 employees), and January 2022 (59 patients and 203 employees), which corresponded to the first, second, and fifth COVID-19 waves in Russia.&#x0D; Conclusion. The analysis of data obtained at the National Research Center for Hematology demonstrated a wave-like SARS-CoV-2 RNA detection rate in employees and patients of the Center, which corresponded to the general trend in Russia. The SARS-CoV-2 RNA detection rate did not depend on sex of subjects under study and was not significantly different in the groups of tumor and non-tumor hematological patients. Although the patients in hematological hospital are more exposed to the risk of severe infectious complications, they showed laboratory markers for COVID-19 less frequently than the Center employees.

Serum IgG and IgA level in children with acute lymphoblastic leukaemia and its relation with outcome in induction chemotherapy

Background: Immunosuppression in children with Acute Lymphoblastic Leukaemia (ALL) escalates vulnerability to severe infectious complications which leads to higher morbidity and mortality rates among patients. Immunoglobulins are important part of defence mechanism of the body contributing to the humoral immunity. Of all the immunoglobulins, IgG and IgA represents most common type of antibody in blood circulation and provides most long-lived antibody-based immunity against invading pathogens. In earlier years, studies have shown that, serum immunoglobulins are found to be decreased during chemotherapy and this reduction is related with severe sepsis and death in patients. Early identification of immune status can be much useful for assessment of severity and better risk stratification of the patients. Objective: Evaluation of serum IgG and IgA levels in children with ALL and its relationship with sepsis in induction phase of chemotherapy. Method: This prospective observational study was conducted in the Departments of Paediatric Haematology &amp; Oncology and Department of General Paediatrics, Bangabandhu Sheikh Mujib Medical University, Dhaka. During January 2022 to December 2022, a total 60 paediatric patients of newly diagnosed ALL were included as study population. As control, 30 patients were included in this study from General paediatrics and Paediatric Haematology &amp; Oncology, BSMMU to compare baseline immunoglobulin levels with the study group. Complete history and physical examination of all patients were undertaken, and all prior reports were collected. Serum IgG and IgA level assay was done before starting chemotherapy and at the end of induction chemotherapy in the study group. Patients diagnosed with ALL received chemotherapy modified UK-ALL 2003 protocol. History and data of any event of sepsis, along with the symptoms of complications were taken from all patients during the course of induction chemotherapy. Results: The mean age of the cases were 5.49±3.15 (mean ± SD) years, which ranged from 1.9 to 15 years. Among the cases, 41 patients (68.3%) were male and 19 (31.7%) females. Seven (11.7%) subjects expired during induction chemotherapy. In comparison to the control group the mean IgG level in the study group was lower at baseline and even lower at the end of induction and it was statistically significant (p&lt;0.05). The mean IgG level was low in patients with septic events in comparison with the patients with no septic events. Difference of mean of IgG between septic and aseptic patients was significant only at the end of induction chemotherapy (p&lt;0.05). The mean IgA level was low in study group in comparison with the control group and it was statistically significant (p&lt;0.05) only at the end of induction chemotherapy. The mean IgA level was low in patients with septic events in comparison with the patients with no septic events. Difference of mean of IgA between septic and aseptic patients was significant (p&lt;0.05). Based on the receiver-operator characteristic (ROC) curves of change of S. IgG, with a cut off value 50% decreased from baseline having 68.8% sensitivity and 29.7% specificity for prediction of sepsis. Considering change of S. IgA with a cut off value 50% decreased from baseline having 67.6% sensitivity and 27.5% specificity for prediction of sepsis. Conclusion: In our study, the mean IgG and IgA level of the cases were low in comparison to the control group. The mean IgG and IgA level of the patients were lower who had infectious complications, and it was more marked after induction chemotherapy. Therefore, evaluation of immunoglobulin profiles is recommended to be considered in patients with ALL in further studies.

Exploring adjunctive therapies for cerebral malaria.

Cerebral malaria (CM) is one of the most severe complications of malaria infection characterized by coma and neurological effects. Despite standardized treatment of malaria infection with artemisinin-based combination therapies (ACT), the mortality rate is still high, and it primarily affects pediatric patients. ACT reduces parasitemia but fails to adequately target the pathogenic mechanisms underlying CM, including blood-brain-barrier (BBB) disruption, endothelial activation/dysfunction, and hyperinflammation. The need for adjunctive therapies to specifically treat this form of severe malaria is critical as hundreds of thousands of people continue to die each year from this disease. Here we present a summary of some potential promising therapeutic targets and treatments for CM, as well as some that have been tested and deemed ineffective or, in some cases, even deleterious. Further exploration into these therapeutic agents is warranted to assess the effectiveness of these potential treatments for CM patients.

Multiple Cold Abscesses of a Chest Wall with Ribs Destruction in a Hemodialysis Patient

Cold abscess of the chest wall is an uncommon disease that is mainly caused by tuberculous infection. Staphylococcal cold abscesses of the chest wall are extremely rare and usually clinically occult, frequently leading to a delay in diagnosis and consequently severe infectious complications. We report an 88-year-old woman with end-stage renal disease, who presented with an exit site infection of a cuffed tunneled dialysis catheter caused by methicillin-resistant Staphylococcus aureus (MRSA). Despite the removal of the catheter and administration of antibiotics, she developed refractory MRSA bacteremia. Computed tomography (CT) of the chest revealed septic thrombophlebitis with metastatic cold abscesses of the chest wall and ribs destruction. Although CT-guided drainage and vancomycin therapy eliminated MRSA bacteremia, the chest wall abscesses did not resolve. Patients fitted with a central venous dialysis catheter are at risk of septic thrombophlebitis with metastatic cold abscesses of the chest wall that are resistant to antibiotic therapy. Early identification is based on serial blood cultures and prompt CT scans. Surgical management coupled with antibiotic therapy can eradicate the source of infection and improve patients’ outcomes.

A clinical case of viral myocarditis associated with sars-cov-2 in a health worker

The study of various pathological conditions associated with COVID-19 remains an urgent task. In occupational medicine, COVID-19 is considered as a new biological factor that can occur not only in the environment, but also in production conditions. Medical workers are at an increased risk of infection with the SARS-CoV-2 virus when performing their professional duties, while a new coronavirus infection can be considered as an occupational disease. The presence of severe complications of a new coronavirus infection leading to disability gives relevance to the analysis of the features of occupational diseases of medical workers in order to improve their diagnosis, improve prevention, treatment and rehabilitation. The most important manifestation of a new coronavirus infection is a lesion of the cardiovascular system, one of the possible variants of which may be the development of myocarditis. In the Samara region in 2021–2022, 10 cases of chronic occupational diseases associated with a new coronavirus infection that caused permanent disability were identified to medical workers. Of these, viral myocarditis was diagnosed in four cases and inflammatory dilated cardiomyopathy in one case. The presented clinical case reflects one of the possible serious complications of coronavirus infection – myocarditis, which led to the development of cardiac arrhythmias. The article presents the principles and results of a medical examination conducted in order to establish a causal relationship of the disease with the professional activity of a medical worker. The need for a multidisciplinary approach to the diagnosis of manifestations, treatment of COVID-19 and its complications, with the mandatory participation of a cardiologist, improvement of the examination of the connection of COVID-19 with the profession and admission to work in conditions of high risk of infection with SARS-CoV-2 medical workers is emphasized.

Liver, renal, genitourinary and diabetic ketoacidosis risks among new users of empagliflozin versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Post-authorization safety study based on multinational cohorts.

To estimate risks of diabetic ketoacidosis (DKA), acute liver injury (ALI), acute kidney injury (AKI), chronic kidney disease (CKD), severe complications of urinary tract infection (UTI) and genital infection (GI) among patients with type 2 diabetes initiating empagliflozin versus those initiating a dipeptidyl peptidase-4 (DPP-4) inhibitor. In this large multinational, observational, new-user cohort study in UK, Danish and US healthcare data sources, patients initiated empagliflozin or a DPP-4 inhibitor between August 2014 and August 2019, were aged ≥18 years, and had ≥12 months' continuous health plan enrolment. Incidence rates by exposure and incidence rate ratios, adjusted for propensity-score deciles, were calculated. In total, 64 599 empagliflozin initiators and 203 315 DPP-4 inhibitor initiators were included. There was an increased risk [pooled adjusted incidence rate ratios (95% confidence interval)] of DKA [2.19 (1.74-2.76)] and decreased risks of ALI [0.77 (0.50-1.19) in patients without predisposing conditions of liver disease; 0.70 (0.56-0.88) in all patients] and AKI [0.54 (0.41-0.73)]. In the UK data, there was an increased risk of GI [males: 4.04 (3.46-4.71); females: 3.24 (2.81-3.74)] and decreased risks of CKD [0.53 (0.43-0.65)] and severe complications of UTI [0.51 (0.37-0.72)]. The results were generally consistent in subgroup and sensitivity analyses. Compared with DDP-4 inhibitor use, empagliflozin use was associated with increased risks of DKA and GI and decreased risks of ALI, AKI, CKD and severe complications of UTI. These associations are consistent with previous studies and known class effects of sodium-glucose cotransporter 2 inhibitors, including renoprotective effects and beneficial effects on alanine aminotransferase levels.

Coronavirus infection after blood stem cell transplantation

Background. In March 2020, oncohematologists faced the problem of severe COVID-19 coronavirus infection in patients after a high-dose chemotherapy and autologous or allogeneic bone marrow transplantation. This required a review of issues related to the selection of patients for blood stem cell transplantation (HSCT), the development of new preventive and therapeutic tactics aimed at treating infectious and immunological complications in patients of this category, depending on the nature and status of the underlying disease and the timing of treatment.Aim. To assess the severity, most typical complications and course of COVID-19 in patients during early and late posttransplant periods.Materials and methods. We analyzed the data of patients after HSCT with active coronavirus infection hospitalized in the hematology department from 2020 to 2021. A total of 25 patients were hospitalized: 4 after allogeneic transplantation, 21 after autologous transplantation. According to the timing of HSCT, patients were divided into 2 groups: early period (ETP) (2-90 days after HSCT) - 14 patients, late period (LTP) (3-24 months after HSCT) - 11 patients.Results. Severe coronavirus infection (grades III-IV according to computed tomography) was more often observed in patients in the ETP group (65 %) than in the LTP group (18 %). The incidence of respiratory failure was 70 and 36 % in the ETP and LTP groups, respectively. In the ETP group, agranulocytosis and the development of severe infectious complications (bacterial, fungal and viral) were observed significantly more often than in the LTP group, which required the appointment of reserve groups antibacterial therapy and antifungal therapy. Mortality in the ETP group was 35 %, while no deaths were recorded in the LTP group. The median duration of hospitalization for patients in the ETP and LTP groups was 20 and 13 days, respectively.Conclusion. Patients early after HSCT are at higher risk of developing lower respiratory tract infections, are more likely to require hospitalization in the intensive care unit, and have a greater risk of death from COVID-19. Therapy with genetically engineered biological drugs is not contraindicated in the case of leukopenia and agranulocytosis in this group of patients.

Overview of COVID-19 Infection, Treatment, and Prevention in Children.

Coronavirus disease 2019 (COVID-19), caused by the novel respiratory virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-was declared a global pandemic by the World Health Organization on 11 March 2020. Since then, substantial gains have been made in our understanding of COVID-19 epidemiology, disease presentation, and management. While children tend to have less severe disease courses compared to adults, children can still develop severe COVID-19 infections, particularly in those with underlying medical conditions such as obesity, chronic lung disease, or prematurity. In addition, children are at risk of severe complications of COVID-19 infection, such as multisystem inflammatory syndrome in children (MIS-C) or long COVID. The case definitions of MIS-C and long COVID have continued to evolve with the increased understanding of these new entities; however, improved methods of diagnosis and determination of the optimal management are still needed. Furthermore, with the continued circulation of SARS-CoV-2 variants, there remains a need for clinicians to remain up-to-date on the latest treatment and prevention options. The purpose of this review is to provide an evidence-based review of what we have learned about COVID-19 in children since the start of the pandemic and how best to counsel children and their families on the best methods of prevention.

Applying the EHA/EBMT grading for ICAHT after CAR-T: comparative incidence and association with infections and mortality

AbstractCytopenias represent the most common side effect of CAR T-cell therapy (CAR-T) and can predispose for severe infectious complications. Current grading systems, such as the Common Terminology Criteria for Adverse Events (CTCAE), neither reflect the unique quality of post–CAR-T neutrophil recovery, nor do they reflect the inherent risk of infections due to protracted neutropenia. For this reason, a novel EHA/EBMT consensus grading was recently developed for Immune Effector Cell-Associated HematoToxicity (ICAHT). In this multicenter, observational study, we applied the grading system to a large real-world cohort of 549 patients treated with BCMA- or CD19-directed CAR-T for refractory B-cell malignancies (112 multiple myeloma [MM], 334 large B-cell lymphoma [LBCL], 103 mantle cell lymphoma [MCL]) and examined the clinical sequelae of severe (≥3°) ICAHT. The ICAHT grading was strongly associated with the cumulative duration of severe neutropenia (r = 0.92, P < .0001), the presence of multilineage cytopenias, and the use of platelet and red blood cell transfusions. We noted an increased rate of severe ICAHT in patients with MCL vs those with LBCL and MM (28% vs 23% vs 15%). Severe ICAHT was associated with a higher rate of severe infections (49% vs 13%, P < .0001), increased nonrelapse mortality (14% vs 4%, P < .0001), and inferior survival outcomes (1-year progression-free survival: 35% vs 51%, 1-year overall survival: 52% vs 73%, both P < .0001). Importantly, the ICAHT grading demonstrated superior capacity to predict severe infections compared with the CTCAE grading (c-index 0.73 vs 0.55, P < .0001 vs nonsignificant). Taken together, these data highlight the clinical relevance of the novel grading system and support the reporting of ICAHT severity in clinical trials evaluating CAR-T therapies.