Severe Clinical Forms Research Articles

Functionalized 1,2,3-triazolium salts as potential agents against visceral leishmaniasis.

Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, being fatal if untreated. In search of a more effective treatment for VL, one of the main strategies is the development and screening of new antileishmanial compounds. Here, we reported the synthesis of seven new acetyl functionalized 1,2,3-triazolium salts, together with four 1,2,3-triazole precursors, and investigated their effect against different strains of L. infantum from dogs and humans. The 1,2,3-triazolium salts exhibited better activity than the 1,2,3-triazole derivatives with IC50 range from 0.12 to 8.66μM and, among them, compound 5 showed significant activity against promastigotes (IC50 from 4.55 to 5.28μM) and intracellular amastigotes (IC50 from 5.36 to 7.92μM), with the best selective index (SI ~ 6-9) and reduced toxicity. Our findings, using biochemical and ultrastructural approaches, demonstrated that compound 5 targets the mitochondrion of L. infantum promastigotes, leading to the formation of reactive oxygen species (ROS), increase of the mitochondrial membrane potential, and mitochondrial alteration. Moreover, quantitative transmission electron microscopy (TEM) revealed that compound 5 induces the reduction of promastigote size and cytoplasmic vacuolization. Interestingly, the effect of compound 5 was not associated with apoptosis or necrosis of the parasites but, instead, seems to be mediated through a pathway involving autophagy, with a clear detection of autophagic vacuoles in the cytoplasm by using both a fluorescent marker and TEM. As for the in vivo studies, compound 5 showed activity in a mouse model of VL at 20mg/kg, reducing the parasite load in both spleen and liver (59.80% and 26.88%, respectively). Finally, this compound did not induce hepatoxicity or nephrotoxicity and was able to normalize the altered biochemical parameters in the infected mice. Thus, our findings support the use of 1,2,3-triazolium salts as potential agents against visceral leishmaniasis.

Maternal-Fetal Implications of SARS CoV-2 Infection during Pregnancy, Viral, Serological Analyses of Placenta and Cord Blood.

Objective: There are few data on the maternal–fetal transmission of SARS-CoV-2 and its outcomes. This study aimed to evaluate pregnancy outcomes of pregnant women infected by SARS-CoV-2, to detect SARS-CoV-2 in placenta and different newborns’ samples and search antibodies in cord blood. Methods: This was a prospective study of pregnant women diagnosed with SARS-CoV-2 infection from May 2020 to May 2021. At delivery, the placentas were investigated for SARS-CoV-2 using RT-PCR, cord blood. Mothers’ blood samples were tested by SARS-CoV-2 serology. PCR of nasopharyngeal, anal and gastric swabs (NPSs) of newborns was performed according to pediatric indications. Results: Among 3626 pregnant women presenting at maternity to deliver, 45 mothers had COVID-19 during their pregnancy or at delivery (32 ± 4.8 years). Most of them were multiparous and in the third trimester. There were 35 (77%) women who remained in ambulatory, while 10 (22%) were hospitalized for severe pneumonia, digestive symptoms, and/or fetal tachycardia. Thirty-eight delivered vaginally, and 7 had a cesarean delivery with normal Apgar scores (9 ± 1.6 at 5 min) and umbilical artery pH (7.22 ± 0.08). Two mothers required ICU admission after cesarean section for fetal and maternal distress. Of the 46 newborns, 6 were premature births (13%) and 5 IUGR (intra-uterine growth restriction,11%). RT-PCR SARS-CoV-2 was positive for 1/30 placental, and 1/33 neonatal anal swabs and negative in all other cases and in gastric swabs. SARS-CoV-2 IgG was positive in 20/41 cord blood samples (49%) and their mothers’ samples. IgM was negative in the 23 cord blood samples. Conclusions: Pregnancy outcomes in women diagnosed with COVID-19 during their pregnancy were favorable in most cases. However, some women with severe clinical forms required hospitalization and ICU admission. Preterm births and intrauterine growth retardations were relatively frequent. Vaginal delivery was possible in most cases. SARS-CoV-2 IgG antibodies were positive and elevated in most cord blood samples of newborns. They are possibly of maternal origin, suggesting a probable mechanism of fetal protection against SARS-CoV-2 infection. No SARS-CoV-2 IgM was found in the cord blood samples. Detection of SARS-CoV-2 in placenta is rare.

Прогностические критерии развития тяжелых клинических форм COVID-19 у работников медицинской организации

Прогностические критерии развития тяжелых клинических форм COVID-19 у работников медицинской организации

Pediatric Clinical Features of Covid-19 in Cameroon

Introduction: The Covid-19 pandemic is a public health emergency characterized by severe acute respiratory distress syndrome. It has many clinical forms and affects all age groups. Despite the magnitude of this pandemic, data from pediatric cohorts in Cameroon remain sparse. Objective: The aim of this study was to describe the clinical presentation of Covid-19 in the pediatric population of the Nkolndongo health district. Materials and method: A cross-sectional study was conducted for a duration of 5 months from January to May 2021 and covered a period of 9 months (March to December 2020). All patients aged 0 to 19 years, suspected of having Covid-19, confirmed by real-time RT-PCR targeting the N and ORF1 ab viral genes and managed in the Nkolndongo health district were included. The results were analyzed using IBM SPSS.23.0 software and the data expressed as frequencies, percentages, and means. The threshold of statistical significance was set at 0.05. Results: This study revealed that 48 patients out of 154 suspected cases were tested positive. The most affected age group was adolescents aged 13 - 19 years (92.85%). The most frequent symptoms were cough (33%), fever (42%) and nasal discharge (25%). Infants were the least affected. 58% of patients were asymptomatic, 47.91% were in mild stage, 8.33% in moderate stage and 4.16% in severe stage. All the children tested positive survived. Patients with comorbidity were 20 times more likely to develop moderate to severe clinical forms, this being statistically significant. Conclusion: The clinical presentation reported mainly fever, cough and anterior nasal discharge. There was a significant association between the presence of comorbidity and the moderate to severe degrees of severity.

Etiological pattern of community-acquired pneumonia related to the new coronavirus infection COVID-19 pandemic in the Saratov Region

Community-acquired pneumonia is a polyetiological infectious disease of bacterial or viral nature. In most cases, it is caused by pathogens such as Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Staphylococcus aureus, Legionella spp. However, despite that a wide range of modern diagnostic methods have been introduced into laboratory practice, the etiology of the disease can be determined only in 40–60% of cases. Here, we analyzed the causative agents of community-acquired pneumonia and relevant markers samples of clinical material collected from patients undergoing treatment in the medical facilities of the city of Saratov and the Saratov Region during the period from July to August, 2020, coupled to increase number of cases of new coronavirus infection COVID-19. Clinical material (oropharyngeal swabs, saliva, sputum, blood and blood serum) was obtained from 129 patients and investigated by using microbiological, immunoserological and molecular genetic methods. For this, there were used transport and nutrient media, diagnostic drugs, reagents, discs with antibacterial domestic and foreign drugs registered in the Russian Federation. As a result, 82 (63.6%) patients were found to have markers of the pathogen COVID-19 (viral RNA or specific antibodies of IgM and/or IgG classes), whereas 42% of cases had overlapped RT-PCR and ELISA data. There was a predominance of severe clinical forms of the disease in the group of patients with pneumonia caused by SARS-CoV-2 virus (17.1%), compared with pneumonia of another etiology (12.8%). No marked differences in specific pattern of the accompanying microflora and its sensitivity to antibacterial agents were observed in persons with/without markers of COVID-19. While being examined by bacteriological methods, S. aureus, K. pneumoniae, S. pneumoniae, M. pneumoniae, Acinetobacter spp., both in monoculture and in associations, were isolated from samples of clinical material collected from the majority of patients. In 49.6% of cases, pathogenic microflora, including pathogens causing community-acquired pneumonia, has not been identified, which may be due to the use of antibacterial drugs before the collection of clinical material and treatment applied due to comorbid chronic diseases.

Diabetes as a predictive factor for severe form and high mortality risk of COVID-19: Retrospective cohort study of 188 cases

IntroductionSince the appearance of the first case of the SARS CoV 2 infection, several studies have been conducted to identify the predictive factors of mortality in patients with COVID-19. According to previous reports, diabetes seems to be associated with severe clinical forms of the new coronavirus (SARS CoV 2).Our study aimed to identify the epidemiological, clinical, radiological and prognostic profile of diabetic patients with COVID-19. MethodsThis retrospective study included diabetic patients diagnosed with COVID-19 and admitted to the Resuscitation Department of our university hospital center From Mars 1st 2020, to December 31st, 2020. Results and discussionIn this study, we collected the data of 600 patients admitted to the Anesthesia and Resuscitation Department of the Mohammed VI University Hospital of Oujda, a group of 188 (31.3%) had diabetes.The median age of our patients was 67 [25–75]. Were noted in the majority, of patients 69.6% with diabetes have developed a severe or critical injuries in the Chest CT Scan. Furthermore, we found that the mortality rate in this category of patients was higher 65/188 (34.60%) compared to non-diabetic patients, 130/412 (31.60%) (34.60%vs 31.60%; p: 0.464). ConclusionBased on the results of this retrospective study, we concluded that diabetes is predictive factor for the need of an intensive care as well as a high risk of mortality related to COVID-19.Practically speaking, diabetic patients should be monitored more closely and need an aggressive preventive management protocols in order to prevent severe forms of the disease and a drastic evolution.More research is direly needed to identify patients of a higher risk of developing severe forms of COVID-19.

Chromomycosis: literature review and clinical case

A clinical case of leg skin chromomycosis is described, a review of the literature is given, the main modern medical methods, as well as methods of historical significance are briefly described. The individual links of the pathogenesis of chromomycosis (CM) are described, a list of nosologies to which chromomycosis should be differentiated is presented.Materials and methods. A clinical case of chromomycosis in a 63-year-old patient is presented. The process developed as a result of systematic frequent injury of the shins with sharp parts of plants.Results. The diagnosis of chromomycosis was established on the basis of anamnesis, clinic data, detection of the pathogen in the biopsy material.Conclusions. Thus, CM is a serious deep skin mycosis, which still causes an epidemiologically significant morbidity in workers of agricultural and related fields! It is difficult to treat it, especially in more severe clinical forms. Treatment usually consists of long periods of treatment with antifungal drugs, often associated with physical procedures and immunotherapy. This publication is intended to extract HMM from the list of ′forgotten diseases′ at least for a short time!

Protective Efficacy in a Hamster Model of a Multivalent Vaccine for Human Visceral Leishmaniasis (MuLeVaClin) Consisting of the KMP11, LEISH-F3+, and LJL143 Antigens in Virosomes, Plus GLA-SE Adjuvant.

Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, fatal if untreated. Vaccination is the most cost-effective approach to disease control; however, to date, no vaccines against human VL have been made available. This work examines the efficacy of a novel vaccine consisting of the Leishmania membrane protein KMP11, LEISH-F3+ (a recombinant fusion protein, composed of epitopes of the parasite proteins nucleoside hydrolase, sterol-24-c-methyltransferase, and cysteine protease B), and the sand fly salivary protein LJL143, in two dose ratios. The inclusion of the TLR4 agonist GLA-SE as an adjuvant, and the use of virosomes (VS) as a delivery system, are also examined. In a hamster model of VL, the vaccine elicited antigen-specific immune responses prior to infection with Leishmania infantum. Of note, the responses were greater when higher doses of KMP11 and LEISH-F3+ proteins were administered along with the GLA-SE adjuvant and/or when delivered within VS. Remarkably, hamsters immunized with the complete combination (i.e., all antigens in VS + GLA-SE) showed significantly lower parasite burdens in the spleen compared to those in control animals. This protection was underpinned by a more intense, specific humoral response against the KMP11, LEISH-F3+, and LJL143 antigens in vaccinated animals, but a significantly less intense antibody response to the pool of soluble Leishmania antigens (SLA). Overall, these results indicate that this innovative vaccine formulation confers protection against L. infantum infection, supporting the advancement of the vaccine formulation into process development and manufacturing and the conduction of toxicity studies towards future phase I human clinical trials.

Steroid-resistant Acute Generalized Exanthematous Pustulosis Mimicking Generalized Pustular Psoriasis Successfully Treated by Methotrexate

Acute generalized exanthematous pustulosis is a rare drug-induced eruption that is characterized by sterile non-follicular pustules arising on an often edematous diffuse erythematous background. Generalized pustular psoriasis is an acute and severe clinical form of psoriasis presenting as pustular eruption with erythematous base. Differentiating both diseases is often challenging because of their clinical and histopathological similarities. A 62-year-old woman presented with pustular eruption and fever three days after taking propyphenazone. Laboratory findings revealed leukocytosis and neutrophilia. Histopathological findings revealed a subcorneal spongiform pustule filled with neutrophils and perivascular inflammatory cell infiltration with neutrophils in the dermis. She was initially treated with systemic steroids, however, the lesions showed insignificant improvement. Treatment was then shifted to methotrexate which resulted in a dramatic clinical improvement.

A modern approach to the diagnosis of tuberculous spondylitis (literature review)

Objective — provide a systematic analysis of the scientific literature on the current state of diagnosis of patients with tuberculous spondylitis (TS), and identify prospects for improving the diagnosis of this disease. Materials and methods. To carry out this work, we analyzed 118 literature sources from the Pub Med database on the records of Diagnosis of extrapulmonary tuberculosis. Diagnosis of tuberculous spondylitis, and 26 of them tacked for detailed study. Results and discussion. It was found that TS is the most severe clinical form of osteoarticular tuberculosis (OATB), which is a serious medical and social problem. The percentage of diagnostic errors in TS is very high and its level in recent decades has a clear tendency to increase. The diagnostic pause in this disease usually lasts at least three months. Clinico-radiological examinations are the most accessible and widely used in the world, being the basis for the diagnosis of OATB. From the standpoint of evidence-based medicine, a verified (proven) diagnosis of OATB should be based on data from bacteriological and histological examination of pathological material. Quite often the course of the TS is accompanied by the phenomena of pathomorphosis, which significantly complicates the differential diagnosis. In scientific publications, insufficient attention is paid to the issue of etiological diagnosis of the disease, but traditional methods of clinical and radiological studies have a significant percentage of diagnostic errors. Conclusions. Diagnosis of TS in modern conditions in the vast majority of cases occurs at a later stage (in the advanced form), which causes significant difficulties in the treatment this category of patients.It is important to improve the methods of etiological diagnosis of TS with the following studies sensitivity of the pathogen to antibacterial drugs, which is one of the main conditions for successful treatment.

Diagnosis and Causative Species of Visceral Leishmaniasis in Southwest Saudi Arabia.

Visceral leishmaniasis (VL) is the most severe clinical form of the disease and has been reported in the Jazan region of southwest Saudi Arabia. This study aimed to diagnose VL by real-time polymerase chain reaction (PCR) and the direct agglutination test (DAT) and to identify the causative Leishmania species. A total of 80 participants, including 30 suspected VL patients, 30 healthy endemic control individuals, and 20 malaria disease controls, were enrolled in this study. Blood samples were collected and tested for Leishmania DNA by real-time PCR and for antibody by the DAT. Sequencing of some amplified PCR products was used to identify the causative Leishmania species. The diagnosis of VL was successfully achieved by both real-time PCR and by DAT with 100% sensitivity. Leishmania donovani and Leishmania infantum species were detected by sequencing both by the kDNA and ITS1 target genes, followed a BLASTn search. The detection of VL antibody by the DAT followed by the confirmatory detection of Leishmania DNA in patient blood by PCR could promote the adoption of the much less invasive and more sensitive methods for the routine diagnosis of VL. Further study with high sample volume to evaluate the PCR and the DAT are needed, to generate more robust evidence. Based on the sequencing results, emerging studies on VL should focus on the causative Leishmania species, reservoirs, and vectors that are important in the study area.

Is Antibody-Dependent Enhancement of Trypanosoma cruzi Infection Contributing to Congenital/Neonatal Chagas Disease?

The newborns of women infected with the parasite Trypanosoma cruzi (the agent of Chagas disease) can be infected either before birth (congenitally), or after birth (as e.g., by vector route). Congenital Chagas disease can induce high levels of neonatal morbidity and mortality. Parasite-infected pregnant women transmit antibodies to their fetus. Antibodies, by opsonizing parasites, can promote phagocytosis and killing of T. cruzi by cells expressing FcγR, on the mandatory condition that such cells are sufficiently activated in an inflammatory context. Antibody-dependent enhancement (ADE) is a mechanism well described in viral infections, by which antibodies enhance entry of infectious agents into host cells by exploiting the phagocytic FcγR pathway. Previously reported Chagas disease studies highlighted a severe reduction of the maternal-fetal/neonatal inflammatory context in parasite-transmitting pregnant women and their congenitally infected newborns. Otherwise, experimental observations brought to light ADE of T. cruzi infection (involving FcγR) in mouse pups displaying maternally transferred antibodies, out of an inflammatory context. Herein, based on such data, we discuss the previously unconsidered possibility of a role of ADE in the trans-placental parasite transmission, and/or the development of severe and mortal clinical forms of congenital/neonatal Chagas disease in newborns of T. cruzi-infected mothers.

Clostridium difficile-ассоциированный колит: обзор литературы, клинический случай

В статье приведены современные представления об инфекции Clostridium difficile (C. difficile): приводится современная классификация, разбираются вопросы эпидемиологии, этиологии, патогенеза кишечных нарушений, клинические аспекты этого заболевания, а также лабораторные, эндоскопические, морфологические проявления. Представлены современные международные подходы к лечению C. difficile-инфекции. C. difficile-ассоциированный колит — заболевание, развивающееся при нарушении кишечного микробиома с избыточной колонизацией C. difficile, токсины которой вызывают воспаление и повреждение слизистой оболочки толстой кишки и диарею. Прием антибиотиков приводит к угнетению эндогенной микрофлоры и размножению C. difficilе благодаря плазмидам спорообразования; после отмены препаратов споры переходят в вегетативную форму бактерий и начинают вырабатывать токсины; в результате повреждения эндотелия, обширных воспалительных изменений в слизистой оболочке толстой кишки формируются участки некроза на поверхности эпителия с образованием псевдомембран (экссудативных бляшек). Клостридиальная инфекция приводит к широкому спектру клинических проявлений — от бессимптомного носительства, умеренной, неосложненной диареи до угрожающего жизни псевдомембранозного колита — тяжелой клинической формы C. difficile-ассоциированного колита, вызванной токсигенной формой C. difficile, характерным признаком которого являются фибринозные наложения на слизистой оболочке толстой кишки (псевдомембраны), выявленные при эндоскопическом исследовании. Золотым стандартом и наиболее информативным методом верификации диагноза является обнаружение токсинов C. difficile в кале. В диагностике C. difficile-ассоциированного колита важную роль играют также оценка лабораторных показателей, эндоскопическое и морфологическое исследования. При постановке диагноза псевдомембранозного колита лечение необходимо начинать незамедлительно. Первый шаг — отмена антибиотика, вызвавшего диарею. Неотъемлемой частью стандартной терапии пациентов с C. difficile-ассоциированным колитом является антибактериальная терапия, которая должна ограничить колонизацию кишечника C. difficile и оказать противовоспалительное действие. C. difficile наиболее чувствительны к ванкомицину и метронидазолу. Обязательным условием является энтеральное назначение антибиотиков, так как при парентеральном их введении в кишечнике не всегда создается достаточная их концентрация, в связи с чем может не наступить полная санация от C. difficile. В статье показан и проанализирован клинический случай у пациента с данным заболеванием, проходившего лечение в Институте гастроэнтерологии НАМН Украины.

Brain MRI volumetric changes in the follow-up of patients with anti-NMDAr encephalitis

IntroductionAutoimmune anti-NMDAr encephalitis is an antibody-mediated disorder characterized by psychiatric symptoms followed by decreased consciousness, dysautonomia and seizures. The pathophysiology of the disease is related to the internalization of NR1 subtype NMDA receptors and the dysfunction of structures where they are abundant (frontotemporal and insular regions). Some reports suggest the existence of cerebral atrophy in the follow-up of these patients, with conflicting evidence regarding its presence and usefulness as a marker of prognosis. MethodsIn a longitudinal, observational study, all patients with the diagnosis of definite anti-NMDAr autoimmune encephalitis with initial and control MRI studies were included. Conventional MR Brain acquisition was performed using a 3-Tesla Skyra MRI System. Automated brain segmental analysis was performed using the Volbrain volumetry system. The differences between baseline MRI volumetric characteristics and volumetric measures at follow-up was assessed. Results25 patients were included (mean age 26.6, SD 9.6). 44% were females. The mean time between the studies was 24 (SD 21.4, 3–24) months. Significant volume loss was identified in the total brain volume (− 0.02%, p = 0.029), cerebellar volume (− 0.27%, p = 0.048) and brainstem volume (− 0.16%, p = 0.021). ConclusionsThis study supports previous observations regarding volume loss in several brain regions of patients with antiNMDAr encephalitis. Further analyses are required to understand the role of treatment and severe clinical forms, as well as the relationship between volume loss and functional outcome.

NK Cell Subpopulations and Receptor Expression in Recovering SARS-CoV-2 Infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic of coronavirus disease (COVID-19). Whereas in most cases COVID-19 is asymptomatic or pauci-symptomatic, extremely severe clinical forms are observed. In this case, complex immune dysregulations and an excessive inflammatory response are reported and are the main cause of morbidity and mortality. Natural killer cells are key players in the control of viral infection, and their activity is regulated by a tight balance between activating and inhibitory receptors; an alteration of NK activity was suggested to be associated with the development of severe forms of COVID-19. In this study, we analyzed peripheral NK cell subpopulations and the expression of activating and inhibitory receptors in 30 patients suffering from neurological conditions who recovered from mild, moderate, or severe SARS-CoV-2 infection, comparing the results to those of 10 SARS-CoV-2-uninfected patients. Results showed that an expansion of NK subset with lower cytolytic activity and an augmented expression of the 2DL1 inhibitory receptor, particularly when in association with the C2 ligand (KIR2DL1-C2), characterized the immunological scenario of severe COVID-19 infection. An increase of NK expressing the ILT2 inhibitory receptor was instead seen in patients recovering from mild or moderate infection compared to controls. Results herein suggest that the KIR2DL1-C2 NK inhibitory complex is a risk factor toward the development of severe form of COVID-19. Our results confirm that a complex alteration of NK activity is present in COVID-19 infection and offer a molecular explanation for this observation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12035-021-02517-4.

Adaptive immune responses to SARS-CoV-2 in recovered severe COVID-19 patients.

BackgroundThere is an imperative need to determine the durability of adaptive immunity to SARS-CoV-2. We enumerated SARS-CoV-2-reactive CD4+ and CD8+ T cells targeting S1 and M proteins and measured RBD-specific serum IgG over a period of 2–6 months after symptoms onset in a cohort of subjects who had recovered from severe clinical forms of COVID-19.Patients and MethodsWe recruited 58 patients (38 males and 20 females; median age, 62.5 years), who had been hospitalized with bilateral pneumonia, 60% with one or more comorbidities. IgG antibodies binding to SARS-CoV-2 RBD were measured by ELISA. SARS-CoV-2-reactive CD69+-expressing-IFNγ-producing-CD4+ and CD8+ T cells were enumerated in heparinized whole blood by flow cytometry for ICS.ResultsDetectable SARS-CoV-2-S1/M-reactive CD69+-IFN-γ CD4+ and CD8+ T cells were displayed in 17 (29.3%) and 6 (10.3%) subjects respectively, at a median of 84 days after onset of symptoms (range, 58–191 days). Concurrent comorbidities increased the risk (OR, 3.15; 95% CI, 1.03–9.61; P = 0.04) of undetectable T–cell responses in models adjusted for age, sex and hospitalization ward. Twenty-one out of the 35 patients (60%) had detectable RBD-specific serum IgGs at a median of 118 days (range, 60–145 days) after symptoms onset. SARS-CoV-2 RBD-specific IgG serum levels were found to drop significantly over time.ConclusionA relatively limited number of subjects who developed severe forms of COVID-19 had detectable SARS-CoV-2-S1/M IFNγ CD4+ and CD8+ T cells at midterm after clinical diagnosis. Our data also indicated that serum levels of RBD-specific IgGs decline over time, becoming undetectable in some patients.

Частота формирования синдрома «сухого глаза» в зависимости от длительности применения гипотензивных капель у пациентов с первичной открытоугольной глаукомой

Aim. To conduct a clinical assessment of the incidence of dry eye syndrome (DES) in patients with primary open-angle glaucoma (POAG), depending on the timing of the use of local antihypertensive therapy. Methods. The main group included 45 patients (45 eyes) with POAG. Inclusion criteria - use of local antihypertensive therapy for at least one month; absence of previous laser and microsurgery operations, systemic pathology that can cause DES (thyroid lesions, diabetes mellitus, autoimmune and rheumatoid diseases). The patients’ age averaged 61.2±8.7 years (from 47 to 82 years). There were 29 men and 16 women. The design of the work consisted of a comparative assessment of the frequency of DES formation in the studied groups and subgroups, as well as the degree of its severity. Results. The results of the study showed that with an increase in the duration of the use of local antihypertensive drugs by patients with POAG the incidence of DES development increases. Moderate changes in the studied functional parameters of the ocular surface were recorded as early as 1-3 years from the start of antihypertensive therapy. Especially often DES was formed in the 3rd subgroup and proceeded in more severe clinical forms. Conclusion. The initial statistically insignificant changes in the indicators of the state of the ocular surface in patients with POAG using local antihypertensive therapy took place at the time of their instillation from 1 to 3 years. Most often, according to our data, DES developed in patients with POAG after three years of using antihypertensive drugs (9 out of 15 patients). Key words: dry eye syndrome; glaucoma; antihypertensive therapy.

Post-coronavirus disease 2019 children in Sarajevo-Lessons learnt?

Introduction: A new disease coronavirus disease 2019 (COVID-19) is with insufficiently known epidemiological characteristics and spectrum of clinical expression in childhood. Children have a lower incidence of this disease with a predominance of mild forms but severe clinical forms, such as among others, acute respiratory distress syndrome, and multisystem inflammatory syndrome may occur, according to current findings. In children with atypical symptomatology and positive or suspicious epidemiological survey, practitioners should consider the possibility of COVID-19.Methods: This study formed the group of 70 children previously healthy or with no pre-existing heart disease from Sarajevo with positive post-COVID history. Following the history of disease and epidemiological data, establishing the 1st day of disease or contact, a detailed cardiovascular examination was performed, including parameters of body weight, height, oxygen saturation, pulse, blood pressure, 12 leads electrocardiogram (ECG) done on Schiller machine, values of polymerase chain reaction (PCR), or serological test on corona: Immunoglobulin (Ig) G and IgM. Echocardiographic examination was done using M, B mode, color, continuous wave, and pulse wave Doppler in standard views. Laboratory blood tests included: Full blood count, creatinine phosphokinase myofibril, creatinine phosphokinase, lactate dehydrogenase; liver enzymes, D dimer, C reactive protein, and urine.Results: Majority of children (64.3%) were asymptomatic. ECG was normal in relation to patients’ age except in eight patients (intermittent palpitations on exertion) who had short PR interval 0.120–0.140 ms, with no delta wave, with heart rate within the normal range according to age, so 24 h ECG Holter was performed without any significant arrhythmias, incomplete right branch block has been documented in 12%, monofocal ventricular ectopic extrasistoly in 15%. Mean IgG, as a marker of infection, showed a statistical significance when compared between age Groups I and II (<5) and older groups: III, IV, and V (>5) (p < 0.05; p = 0.043). PCR test was negative in 9 (70 children), although they showed symptoms, COVID-19 infection clinical data, and positive laboratory findings. Echocardiogram was normal in all patients with normal ejection fraction of the left ventricle.Conclusion: The possibility of COVID-19 in children with atypical symptomatology and positive or suspicious epidemiological survey should be in the focus of every pediatrician at primary care institutions nowadays. Cardiovascular assessment should always be an option in post-COVID patients. Immunological assessment is necessary in post-COVID patients in order to gain a further understanding of PTS status. With more serological testing for severe acute respiratory syndrome coronavirus 2 physicians would be able to make a diagnosis of COVID-19 timely and more accurately, as well as to evaluate the role of asymptomatic children in disease transmission and to assess the importance of protective antibodies and the distribution of COVID-19.

New possibilities of systemic therapy of plaque psoriasis with the IL23p19 inhibitor risankizumab

Introduction. There is a trend towards rising incidence of psoriasis and increase in the degree of incidence of severe, atypical and treatment-resistant clinical forms of psoriasis in the Russian Federation. In this regard, cases of early disability of patients and deterioration of their quality of life are recorded, which determines the medical and social significance of this disease. In the last few years, a much deeper understanding of the pathogenesis of psoriasis has been gained. This is especially true of the role of T-helper 17 cells, the role of the IL-23 cytokine in the development of the disease, which has resulted in the development of new classes of biological drugs, which creation introduced significant changes in the treatment of psoriasis that has become more effective, safer and convenient for patients. More new biologics undergo clinical trials and receive approvals with each passing year. Among them is risankizumab, interleukin-23 inhibitor, which is a safe and effective drug for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis in adult patients. Interleukin-23 inhibitors are not required to be administered as often as interleukin-17 inhibitors and may have a more favourable safety profile without an increased risk of candidiasis or inflammatory bowel disease. Overall, these highly effective drugs contribute to the improvement of the long-term efficacy of psoriasis therapy due to relief of skin lesions and joint symptoms, as well as to the enhancement of patients’ quality of life and lengthening of remissions.Purpose. To analyse key information about risankizumab using the results of clinical trials published in the current scientific literature.Materials and methods. This analysis used literature sources from the international medical databases: PubMed, Cochrane Library, MEDLINE.Results. Presently, a number of phase III registrational trials of risankizumab in 2,109 patients with plaque psoriasis have been published: UltIMMa-1, UltIMMa-2, IMMvent and IMMhance, as well as an additional side by side comparative study of risankizumab with secukinumab (IMMerge) in 327 patients with plaque psoriasis. The results of these studies were used as the grounds for approval of risankizumab for the treatment of patients with moderate to severe plaque psoriasis and psoriatic arthritis by the Russian Ministry of Health on September 14, 2020. There have also been several reports of interim results of the open-label enhanced LIMMitless study, which included patients from pivotal studies. Our records show that the percentage of patients receiving risankizumab for 3 years (172 weeks) and maintaining PASI 90 and PASI 100 was 88 and 63%, respectively, and the percentage of those maintaining sPGA 0/1 was 88%.Conclusion. The analysed data showed that risankizumab is one of the most effective target drugs for the treatment of psoriasis and psoriatic arthritis, it has a favourable safety profile and a more convenient dosage regimen as compared with other genetically engineered biologic drugs (GEBD) (the recommended dose of Skyrizi is 150 mg (two 75 mg injections) administered by subcutaneous injection at week 0, week 4, and every 12 weeks thereafter).

IMPACT OF DISEASE TREATMENT ON THE OUTCOME OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) WITH COVID‐19: A MULTICENTER STUDY ON BEHALF OF GELLC

Introduction: Patients (pts) with CLL are at risk of more severe COVID-19 clinical forms and worse survival compared to general population. Besides age and comorbidities, CLL treatments can aggravate an immune status otherwise impaired by the disease itself, which could also influence COVID-19 outcome. The aim of our study was to focus on COVID-19 outcomes according to CLL treatment at the time of COVID-19. Patients and Methods: 321 pts with CLL and COVID-19 from 52 Spanish centers were included. Pts were classified in two cohorts according to time of COVID. First cohort were pts from the first wave (1W) of COVID and included 166 pts infected from March 1 to May 31, 2020; the second wave (2W) included 155 patients infected from August 1 to January 31, 2021. Clinical characteristics, CLL treatment status and COVID outcomes were analyzed and reported from the whole series, and from the two cohorts separately. Finally, we collected data referred to SARS-CoV-2 infection status and response, including Polymerase Chain Reaction (PCR) negativity for COVID19 and presence of serum neutralizing antibodies. Results: Median age was 73 years (37-94) and 65% (n = 210) were male. A total of 160 (50%) were on watch and wait (W&W) approach, 61 (19%) were previously treated [26 of them (43%) ended treatment <12 months before COVID], and 100 (31%) were on active CLL treatment at the time of COVID diagnosis (72 BTKi, 16 BCL-2i, 9 alkylating drugs and 3 others). 1W cohort presented with more pneumonia (87% vs. 72%, p = 0.001), supplemental oxygen requirements (82% vs. 70%, p = 0.018) and admissions (92% vs 71%, p < 0.01) than those from 2W. Conversely, no significant differences in overall survival (OS) were found between the two cohorts. Considering the whole series, age and D-dimer levels were statistically associated with OS (p < 0.01). In addition, W&W patients presented better OS compared to patients on active or previous CLL treatment finished <12 months prior COVID infection (HR 1.7 [95% CI 1.09-2.81], p = 0.02). Finally, median time to PCR negativity was 33 days for W&W patients compared to 55 days for treated patients (p = 0.01) (Figure 1). Serological test was performed in 84 out of 321 cases (26%), with 47 patients (56%) becoming positive (IgG+). No significant differences in terms of seroconversion were found according to CLL treatment status. With a median follow-up of 60 days (range 0-320), no SARS-CoV-2 reinfections were reported and, among IgG+ cases, none of the patients became seronegative. Conclusions: CLL remains a high-risk disease for COVID-19 regardless of best understanding of SARS-CoV-2 management and improved health-care conditions during the 2W. Of note, patients in W&W have better OS compared to those previously treated or in active treatment at COVID diagnosis, suggesting that CLL treatment is worsening COVID-19 outcomes. Finally, PCR clears earlier in W&W patients than in treated cases. Time to PCR negativity according to CLL status Keywords: Chronic Lymphocytic Leukemia (CLL) No conflicts of interest pertinent to the abstract.