Acute Clinical Manifestations Research Articles

Cardiac Myosin-binding Protein-C as a Biomarker in the Early Diagnosis of Acute Coronary Syndrome and Differentiation of Its Types

Abstract Background: Coronary heart disease (CHD) is primarily caused by atherosclerotic lesions within the intima of coronary arteries and acute coronary syndrome (ACS) is the main acute clinical manifestation of CHD. The ACS is manifested in one of three subtypes and it is the leading cause of mortality worldwide. The three subtypes of ACS include: acute myocardial infarction (MI) with the electrocardiogram (ECG) presenting ST-segment elevation (STEMI), MI with no ST-segment elevation on ECG (NSTEMI), and the third subtype is unstable angina (UA). The early diagnosis of is important in decreasing morbidity and mortality in ACS patients. Objective: To investigate the role of serum level of cardiac myosin-binding protein-C (cMyC), compared with high-sensitivity cardiac troponin-I (hsCTn-I) in the early diagnosis of ACS and differentiation of its subtypes. Materials and Methods: One hundred and twenty patients (72 males and 48 females), aged ≥30 years selected from those who were admitted to emergency department (ED) of Al-Yarmouk teaching hospital and diagnosed with ACS by cardiologists. The duration between the onset of chest pain and admission to ED should not exceed 3 h in any cohort. Apparenty healthy subjects as controls group for the study were recruited from those who had no current illness, particularly CHD, no other systemic disease and each had a normal ECG. For each study subject, cMybp-C and hsCT-I serum levels on admission were measured using the enzyme-linked immunosorbent assay kits. For each ACS patient, serum level of hsCTn-I level was measured 3 h after admission. Results: The comparison of cMybp-C levels among study groups revealed an overall significant difference and on paired comparison of study groups, the cMybp-C mean level was significantly higher in each ACS subgroup than in controls group (P < 0.001), except in UA subgroup versus controls group. The cMybp-C levels showed a significant positive correlation with hsCT-I levels on admission in STEMI and NSTEMI subgroups but not in UA subgroup. The cMybp-C levels also showed a significant positive correlation with hscT-I levels 3 h after admission in STEMI and NSTEMI subgroups but not in UA subgroup. On receiver operating characteristic curve analysis, the cMybp-C level had a better diagnostic accuracy than hscTn-I on admission in differentiation of patients with “STEMI or NSTEMI” from those with UA or from controls. Conclusion: Serum cMybp-C mean level is significantly higher in ACS patients with STEMI and NSTEMI than in controls and the increase was more significant than hsCTn-I mean level on admission, so it could help the early diagnosis of ACS patients. The serum levels of cMybp-C also had a better diagnostic accuracy than hsCTn-I on admission in differentiation of ACS patients with STEMI or NSTEMI from those with UA or from controls.

Evolving Concepts of the SCORE System: Subtracting Cholesterol from Risk Estimation: A Way for a Healthy Longevity?

The role of cholesterol, mainly low-density lipoproteins (LDL-C), as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) is now established and accepted by the international scientific community. Based on this evidence, the European and American guidelines recommend early risk stratification and "rapid" achievement of the suggested target according to the risk estimation to reduce the number of major cardiovascular events. Prolonged exposure over the years to high levels of LDL-C is one of the determining factors in the development and progression of atherosclerotic plaque, on which the action of conventional risk factors (cigarette smoking, excess weight, sedentary lifestyle, arterial hypertension, diabetes mellitus) as well as non-conventional risk factors (gut microbiota, hyperuricemia, inflammation), alone or in combination, favors the destabilization of the atherosclerotic lesion with rupture/fissuration/ulceration and consequent formation of intravascular thrombosis, which leads to the acute clinical manifestations of acute coronary syndromes. In the current clinical practice, there is a growing number of cases that, although extremely common, are emblematic of the concept of long-term exposure to the risk factor (LDL hypercholesterolemia), which, not adequately controlled and in combination with other risk factors, has favored the onset of major cardiovascular events. The triple concept of "go lower, start earlier and keep longer!" should be applied in current clinical practice at any level of prevention. In the present manuscript, we will review the current evidence and documents supporting the causal role of LDL-C in determining ASCVD and whether it is time to remove it from any score.

Hungarian general practice paediatricians’ antibiotic prescribing behaviour for suspected respiratory tract infections: a qualitative study

ObjectivesInappropriate antibiotic prescribing is a major cause of antimicrobial resistance (AMR). The aim of this study was to explore paediatric general practitioners’ (GP Peds) antibiotic prescription practice in suspected respiratory...

Chikungunya virus infection in human microglial C20 cells induces mitochondria-mediated apoptosis.

Chikungunya virus (CHIKV) infection is associated with acute clinical manifestations and chronic joint inflammation. CHIKV has emerged as a significant causative agent of central nervous system (CNS) complications, including encephalitis and related sequelae. Microglial cells, crucial for immune responses and tissue repair in the CNS, play a vital role in the host response to viral infections, with their activation potentially leading to either protection or pathology. In this study, the infection biology of CHIKV in the C20 human microglial cell line was investigated. The permissiveness of C20 cells to CHIKV infection was assessed, and viral replication kinetics were compared to Vero E6 cells. Cytopathic effects of CHIKV infection on C20 cells were examined, along with ultrastructural changes using transmission electron microscopy. Additionally, apoptosis induction, mitochondrial membrane potential, and alterations in cell surface marker expression were evaluated by flow cytometry. CHIKV infection demonstrated permissiveness in C20 cells, similar to Vero cells, resulting in robust viral replication and cytopathic effects. Ultrastructural analysis revealed viral replication, mature virion formation, and distinctive cytoplasmic and nuclear changes in infected C20 cells. CHIKV infection induced significant apoptosis in C20 cells, accompanied by mitochondrial membrane depolarization and altered expression of cell surface markers such as CD11c, CD14, and HLA-DR. Notably, decreased CD14 expression was observed in CHIKV-infected C20 cells. The study findings suggest that CHIKV infection induces apoptosis in C20 microglial cells via the mitochondrial pathway, with significant alterations in cell surface marker expression, particularly CD14 that is linked with apoptosis induction. These observations provide valuable insights into the role of human microglial cells in the host response to CHIKV infection and contribute to the knowledge on the neuropathogenesis of this virus.

Impending thyroid storm caused by hydatidiform mole

Introduction: Thyroid storm is a rare but life-threatening endocrine emergency. It is an acute exaggerated clinical manifestation of thyrotoxic state. We report an impending thyroid storm caused by a hydatidiform mole in a 14-year-old girl. This paper intends to describe hyperthyroidism secondary to molar pregnancy highlighting the rare but essential evaluation of hyperthyroidism. Case: A 14-year-old girl was consulted by the obstetric division to evaluate and manage hydatidiform mole with suspected hyperthyroidism. She had frequent palpitations and tremors for 1 week ago. She also complained of nausea and vomiting 1 week before admission to the hospital. We found a Burch-Wartofsky score of 25, which was categorized as an impending thyroid storm. Laboratory results showed mild anemia, low thyroid stimulating hormone (TSH) levels, high free thyroxine (T4) levels, and markedly elevated beta-human chorionic gonadotropin (beta-hCG) levels, normal Thyroid-stimulating hormone receptor antibodies (TRAb). Other laboratory parameters are mediocre. The ECG results showed sinus tachycardia. A mole tissue biopsy of the uterus confirms the morphology of the hydatidiform mole. These findings established the diagnosis of Impending Thyroid Storm caused by a hydatidiform mole. Conclusion: A hydatidiform mole can cause thyroid storm because the hormone hCG has similar structure to TSH. Doctors should always estimate the possibility of hyperthyroidism in a molar pregnancy.

Oral Chagas Disease in Colombia-Confirmed and Suspected Routes of Transmission.

Chagas disease (CD) remains endemic throughout many regions of Colombia despite implementing decades of vector control strategies in several departments. Some regions have had a significant decrease in vectorial transmission, but the oral ingestion of Trypanosoma cruzi through consumption of contaminated food and drink products is increasingly described. This form of transmission has important public health relevance in Colombia due to an increase in reported acute CD cases and clinical manifestations that often lead to significant morbidity and mortality. Oral CD in Colombia has been associated with the consumption of contaminated fruit juices, such as palm wine, sugar cane, or tangerine juice and water for consumption, or contaminated surfaces where food has been prepared. Another interesting route of oral transmission includes ingestion of unbeknownst infected armadillos' blood, which is related to a traditional medicine practice in Colombia. Some earlier reports have also implemented consumption of infected bush meat as a source, but this is still being debated. Within the Amazon Basin, oral transmission is now considered the principal cause of acute CD in these regions. Furthermore, new cases of acute CD are now being seen in departments where CD has not been documented, and triatomine vectors are not naturally found, thus raising suspicion for oral transmission. The oral CD could also be considered a food-borne zoonosis, and odoriferous didelphid secretions have been implemented in contaminating the human dwelling environment, increasing the risk of consumption of infectious metacyclic trypomastigotes. In this article, we will discuss the complex transmission dynamics of oral CD in Colombia and further examine the unique clinical manifestations of this route of infection. New insights into the oral transmission of Trypanosoma cruzi are being discovered in Colombia, which can help bring increased awareness and a better understanding of this neglected tropical disease to reduce the burden of CD throughout Latin America.

Key clinical manifestations to differentiate Oropouche fever from dengue and other arboviral diseases: a living systematic reviewRevisão sistemática viva das manifestações clínicas da febre do Oropouche: características-chave para diferenciá-la da dengue e de outras arboviroses

To assess the frequency of symptoms in patients with Oropouche fever and compare them with those observed in patients with dengue and other arboviral diseases. A systematic review was conducted following the MOOSE and PRISMA reporting guidelines. The review included studies on acute clinical manifestations in patients with Oropouche fever. Searches were conducted in PubMed, Virtual Health Library, Cochrane Library, and Google Scholar up to September 2024. The symptoms of Oropouche fever were compared to those of dengue and other arboviral diseases. Certainty of evidence was assessed using the GRADE approach. A total of 23 studies covering 3648 patients with Oropouche fever were included. The most frequent symptoms in patients with Oropouche virus infection were fever (97%) and headache (86%). There was no difference in frequency of fever or headache between patients with Oropouche and dengue. However, odynophagia (28%) and abdominal pain (15%) were more frequent in Oropouche than in dengue, with odds ratios (ORs) of 3.20 and 2.50, respectively. Myalgia (69%) and arthralgia (57%) were less frequent in Oropouche fever than in dengue. Fever and headache are common in Oropouche virus infection, but do not help discriminate it from dengue. However, odynophagia and abdominal pain are more frequent in patients with Oropouche fever, while myalgia, arthralgia, and rash are more prevalent in dengue. These findings may aid in differential diagnosis in areas of arboviral co-circulation. Further studies on the recurrence and duration of symptoms are needed to improve diagnostic strategies.

Levels of Serum and Urine Catecholaminergic and Apelinergic System Members in Acute Ischemic Stroke Patients

Objective: To compare levels of catecholaminergic system members, renalase, cerebellin, and their substrates, epinephrine, norepinephrine, and dopamine, and apelinergic system members, apelin, elabela, and nitric oxide in the blood and urine of patients with acute ischemic stroke and healthy controls. Materials and Methods: 42 patients with acute ischemic stroke and 42 age and sex-matched healthy controls were included in the study. Blood and urine samples were collected simultaneously and within the first 24 hours after the onset of acute stroke clinical manifestations and were measured using an ELISA method. Results: The levels of serum and urine cerebellin, renalase, epinephrine, norepinephrine, dopamine, apelin, elebela, and nitric oxide were similar in ischemic stroke and in control groups (P>0.05). Strong correlations were found between renalase, cerebellin, and catecholamine levels in serum and urine (p <0.001) both in stroke patients and controls. There were also strong correlations between apelin, elabela, and NO levels in serum and urine (p <0.001) in the two groups. Conclusion: Serum and urine cerebellin, renalase, epinephrine, norepinephrine, dopamine, apelin, elebela, and nitric oxide levels do not significantly change in the acute phase of ischemic stroke. Strong correlations among renalase, cerebellin, and catecholamines emphasize that these substances act together in healthy individuals and ischemic stroke patients. Similarly, strong correlations between apelin, elabela, and NO indicate that these agents act together in healthy subjects and patients with ischemic stroke.

Transcranial Doppler Ultrasound Role for Patients with Traumatic Brain Injury

Neurologists, neurosurgeons, and neurointensivists, including military, have a large armamentarium of diagnostic and monitoring devices available to detect primary and secondary brain injury and guide therapy in patients with acute traumatic brain injury (TBI) to avoid cerebral ischemia due to the posttraumatic vasospasm (PTV) and intracranial hypertension (ICH). This review summarizes the advantages and the specific roles of transcranial Doppler (TCD) ultrasonography for patients with acute and longterm effects of TBI. In critical care setting numerous publications showed that TCD is predictive of angiographic PTV and onset of ICH. The post TBI status of cerebrovascular reactivity and cerebral hemodynamics also has important implications with regard to the treatment of long-term effects of mild TBI (mTBI). Today it is abundant evidence that TCD is an important tool for monitoring the natural course of acute moderate and severe TBI, for evaluating the effect of medical treatment or intervention, for forecasting, and for identifying high-risk patients for onset of cerebral ischemia after TBI. TCD makes good clinical and economic sense as it is a reliable, quantitative, non-invasive and non-expensive “biomarker” to the acute clinical manifestations of TBI. TCD clinical utilization holds promise for better detection, characterization, and monitoring of objective cerebral hemodynamics changes in symptomatic patients with TBI not readily apparent by standard CT or conventional MRI techniques. TCD utilization will improve the sensitivity of neuroimaging to subtle brain perturbations and combining these objective measures with careful clinical characterization of patients may facilitate better understanding of the neural bases and treatment of the signs and symptoms of TBI. This review summarizes the advantages and the specific roles of TCD ultrasonography for patients with acute and long-term effects of TBI.

Antioxidant Genetic Variants Modify Echocardiography Indices in Long COVID.

Although disturbance of redox homeostasis might be responsible for COVID-19 cardiac complications, this molecular mechanism has not been addressed yet. We have proposed modifying the effects of antioxidant proteins polymorphisms (superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPX1), glutathione peroxidase 3 (GPX3) and nuclear factor erythroid 2-related factor 2, (Nrf2)) in individual susceptibility towards the development of cardiac manifestations of long COVID-19. The presence of subclinical cardiac dysfunction was assessed via echocardiography and cardiac magnetic resonance imaging in 174 convalescent COVID-19 patients. SOD2, GPX1, GPX3 and Nrf2 polymorphisms were determined via the appropriate PCR methods. No significant association of the investigated polymorphisms with the risk of arrhythmia development was found. However, the carriers of variant GPX1*T, GPX3*C or Nrf2*A alleles were more than twice less prone for dyspnea development in comparison with the carriers of the referent ones. These findings were even more potentiated in the carriers of any two variant alleles of these genes (OR = 0.273, and p = 0.016). The variant GPX alleles were significantly associated with left atrial and right ventricular echocardiographic parameters, specifically LAVI, RFAC and RV-EF (p = 0.025, p = 0.009, and p = 0.007, respectively). Based on the relation between the variant SOD2*T allele and higher levels of LV echocardiographic parameters, EDD, LVMI and GLS, as well as troponin T (p = 0.038), it can be proposed that recovered COVID-19 patients, who are the carriers of this genetic variant, might have subtle left ventricular systolic dysfunction. No significant association between the investigated polymorphisms and cardiac disfunction was observed when cardiac magnetic resonance imaging was performed. Our results on the association between antioxidant genetic variants and long COVID cardiological manifestations highlight the involvement of genetic propensity in both acute and long COVID clinical manifestations.

Heart involvement in multisystem inflammatory syndrome in children correlated with SARS-CoV-2 infection: a review by ANMCO/SICP

Acute clinical manifestations of COVID-19 are generally less severe in childhood, however a proportion of them can develop a severe systemic hyperinflammatory syndrome after SARS-CoV-2 infection, known as the multisystem inflammatory syndrome (multisystem inflammatory syndrome in children, MIS-C). Cardiovascular manifestations in MIS-C are frequent (34-82%), including myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. The most affected cases can develop cardiogenic shock needing intensive care unit admission, inotropic support and sometimes even mechanical circulatory support. The elevation of myocardial necrosis markers, the frequently transient left ventricular systolic dysfunction and the presence of changes on magnetic resonance imaging, support the hypothesis of an immune-mediated post-viral pathogenesis similar to myocarditis. Although MIS-C shows excellent short-term survival, further studies are needed to demonstrate complete reversibility of residual subclinical heart damage.

Acute phase clinical manifestations of patients with Vogt-Koyanagi-Harada disease in Southern China

BackgroundsTo characterize the acute phase clinical manifestations and visual outcomes of the patients with Vogt-Koyanagi Harada (VKH) disease in southern China.MethodsIn total, 186 patients with acute-onset VKH disease were recruited. The demographic data, clinical signs, ophthalmic examinations, and visual outcomes were analyzed.ResultsAmong the 186 VKH patients, 3 were diagnosed as complete VKH, 125 as incomplete VKH, and 58 as probable VKH. All patients visited the hospital within 3 months of onset and complained of decreased vision. For the extraocular manifestations, 121 patients (65%) referred neurological symptoms. Anterior chamber activity was negative in most eyes within an onset of 7 days, which increased slightly with onset beyond 1 week. Exudative retinal detachment (366 eyes, 98%) and optic disc hyperaemia (314 eyes, 84%) were commonly observed at presentation. A typical ancillary examination helped with the diagnosis of VKH. Systemic corticosteroid therapy was prescribed. The logMAR best-corrected visual acuity improved significantly from 0.74 ± 0.54 at baseline to 0.12 ± 0.24 at the 1-year follow-up visit. The recurrence rate was 18% in the follow-up visits. Erythrocyte sedimentation rate and C-reactive protein were significantly correlated to VKH recurrences.ConclusionPosterior uveitis, followed by mild anterior uveitis, is the typical initial manifestation in the acute phase of Chinese VKH patients. Visual outcome improvement is promising in most patients receiving systemic corticosteroid therapy in the acute phase. Detection of the clinical features at the initial onset of VKH could facilitate early treatment and better vision improvement.

Tick-borne encephalitis: Acute clinical manifestations and severity in 581 cases from Germany, 2018–2020

Tick-borne encephalitis (TBE) is a growing public health problem with an average of 361 cases notified annually to Germany's passive surveillance system since 2001. We aimed to assess clinical manifestations and identify covariates associated with severity. We included cases notified 2018-2020 in a prospective cohort study and collected data with telephone interviews, questionnaires to general practitioners, and hospital discharge summaries. Covariates' causal associations with severity were evaluated with multivariable logistic regression, adjusted for variables identified via directed acyclic graphs. Of 1220 eligible cases, 581 (48%) participated. Of these, 97.1% were not (fully) vaccinated. TBE was severe in 20.3% of cases (children: 9.1%, ≥70-year-olds: 48.6%). Routine surveillance data underreported the proportion of cases with central nervous system involvement (56% vs. 84%). Ninety percent required hospitalization, 13.8% intensive care, and 33.4% rehabilitation. Severity was most notably associated with age (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02-1.05), hypertension (OR: 2.27, 95%CI: 1.37-3.75), and monophasic disease course (OR: 1.67, 95%CI: 1.08-2.58). We observed substantial TBE burden and health service utilization, suggesting that awareness of TBE severity and vaccine preventability should be increased. Knowledge of severity-associated factors may help inform patients' decision to get vaccinated.

Myocardial infarction and viral triggers: what do we know by now?

Myocardial infarction (MI) is an acute clinical manifestation ischaemic heart disease, which is the leading cause of death worldwide. Infections also have an important burden worldwide, with lower respiratory infections being the worldwide leading cause of death due to communicable diseases. The relationship of MI with viral respiratory infections (including influenza and SARS-CoV-2) as a trigger has been well documented with significant associations. These infections can lead to Type 1 MI, where inflammation and vascular dysfunction, as well as the increased prothrombotic environment lead to atherothrombosis. Type 2 MI may also occur due to an imbalance of oxygen/blood supply and myocardial demand (hypoxaemia, fever, and tachycardia). The data from randomized controlled trials showing a potential benefit of influenza vaccination in coronary artery disease patients should not be ignored. This can be considered a further argument for the association of viral infections (influenza in particular) and MI.

Massive Gastrointestinal Bleeding as a clinical manifestation of Miliary Tuberculosis

Tuberculosis is still a public health problem today and can have acute and chronic manifestations challenging clinics for various medical specialties. Because it’s a disease of multisystem potential, it is often overlooked when outside the respiratory clinical context. As a result, a clinical case report was carried out at the Hospital de Clínicas de Porto Alegre, in 2020, of a patient with voluminous gastrointestinal bleeding as severe acute clinical manifestation of Miliary and Intestinal Tuberculosis. Due to the potential severity of undiagnosed and untreated tuberculosis, high suspicion is suggested at all levels of health systems (whether public or private) with a view to early diagnosis, treatment and prevention of complications resulting from the disease.

Impact of G6pd Deficiency on Sickle Cell Disease in Children in Kinshasa Hospitals: A Case-Control Study

Background and aim: Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency and sickle cell disease are two genetic diseases of the red blood cell that both cause hemolytic anemia. The objective of this study is to determine the clinico- biological impact of G6PD deficiency on sickle cell disease in childrenin Kinshasa. Materials and method: This is a case-control analytical study of 103 G6PD-deficient sickle cell patientsand 309 non-G6PD- deficientsickle cell patients. Analysis of G6PD activitywas performed by ELISA, and hemoglobin electrophoresis by capillaris to confirm sickle cell disease.For all children, sociodemographic, clinical and biological variables were analyzed. Results: The mean age of sickle cell deficient and non-deficient patients was 9.82±4.5 years and 9.48±3.8 years respectively. There were slightly more female sickle cell deficient patients (55.2%) while in the non- deficient group, there was a male predominance (51.8%) but no statistically significant difference (p>0.05). All morbid events occurring in sickle cell patients were greater in the G6PD deficiency group (p˂0.05). Evaluated antecedent complications occurringin sickle cell patients wereassociated with G6PD deficiency (p˂0.05),except for stroke.No statistically significant difference was noted in physicalsigns between sicklecell deficient and non-deficient groups(p>0.05). The hemogramshowed no difference between the two groups in steady state and the hemolysis markers evaluated also showed no significant differences in steady state (p>0.05) between the two groups. Conclusion: G6PD deficiency aggravates the acute clinical manifestations and complications of sickle cell disease withoutaffecting the occurrence of stroke. And has no impact on the hematological parameters of sickle cell disease children in stationary phase.

Risk of malignancy following exposure to Epstein-Barr Virus associated infectious mononucleosis: A nationwide population-based cohort study.

Epstein-Barr virus (EBV) infection has been shown to contribute to oncogenesis and often causes acute clinical manifestation of Infectious mononucleosis (IM). It is unknown whether IM could increase the risk of subsequent malignancies. We aimed to evaluate the association of IM caused by EBV (EBV-IM) with overall and subtypes of malignancy in a large population-based cohort study. This study included 1,419,407 individuals born in Denmark between 1973 and 2016 identified from national registers and 23,057 individuals had IM. The 5,394 of them had confirmed EBV-IM and they were birth date- and sex- matched (1:63) to 1,396,350 non-IM individuals. Cox regression was used to examine the associations of EBV-IM with malignancy. Individuals with a history of confirmed EBV-IM had an 88% increased overall risk of malignancy (hazard ratio [HR]:1·88, 95% confidence interval [CI]: 1·42-2·49) and a five-fold risk of hematologic malignancies (HR 5·04, 95% CI: 3·07-8·25), compared to those without IM. Similar estimates were observed in the sibling analysis. The overall risk of malignancy was greater for EBV-IM with complications (HR 8·93, 95% CI: 3·35-23·81) than that for EBV-IM without complications (HR 1·35, 95% CI: 1·20-1·53). EBV-IM duration was related to increased risk of malignancy in a dose-response way. Notably, the significant elevated risk of overall malignancy was observed in the first two years after EBV-IM onset (rate ratio [RR] 4·44, 95% CI: 2·75-7·17) and attenuated thereafter. EBV-IM was associated with an increased risk in malignancy, particularly hematologic malignancies and in the first two years following IM exposure. Our findings suggest an important time-window for early screening of the EBV-attributed malignancy.

An unexpected effect of teleworking: acute clinical manifestations of a hypersensitivity pneumonitis to home parrots

Abstract Hypersensitivity pneumonitis (HP) is a complex inflammatory and/or fibrotic immune-mediated disease that involves lung parenchyma and small airways caused by an inhaled antigen in susceptible individuals. It is currently the third most frequent interstitial lung disease (ILD) after idiopathic pulmonary fibrosis (IPF) and connective tissue disease with ILD. Diagnosis of HP is often challenging as identifying a causative agent is one of the main arguments in diagnosis along with specific serum IgG testing, suggestive HRCT and/or BAL, and in some cases histopathological findings. However, in up to 60 % of cases, exposure is not identified despite a thorough exposure history. HP is more frequent associated with occupational exposures, up to 20%, but non-occupational environmental exposure remains an important cause. We present a case of bird fancier’s lung that illustrates the challenges and the importance of identifying the culprit antigen as the elimination of exposure in combination with corticosteroids can lead to improvement in lung function, symptoms and leads to a better prognosis and may stop of evolving in sever fibrotic forms of HP.

Prognosis of COVID-19 outcomes and risk prediction for the development of post-COVID syndrome

At the present time, the new laboratory diagnostic markers are required which may predict complications over the post-COVID period, as well as improve diagnostics of post-COVID syndrome in the patients who underwent COVID-19. Despite the fact that changes in respiratory system are the most common manifestations of COVID-19, extrapulmonary manifestations followed by the wide range of persistent symptoms and/or delayed complications may lead to multiple organ lesions of varying severity: from symptomless to fatal forms. A number of symptoms in the developed post-COVID syndrome may persist for 3 weeks, or to be prolonged up to 6 months and later. The purpose of the study was to investigate the informativity of an early integrative diagnostic index developed by us, enabling prediction of the COVID-19 outcome, and potential development of early post-COVID syndrome.
 Peripheral blood samples were examined in 60 patients (38-82 years old) diagnosed with COVID-19 of moderate severity (CT-2.3) during their inpatient treatment; 30 patients (38-62 years old) in the early post-COVID period and 34 patients (38-65 years old) with early post-COVID syndrome. The comparison group consisted of 100 healthy sex- and age-matched volunteers. The IDP, an integrative diagnostic index, was calculated as a marker including the ratio of the relative neutrophil-to-lymphocyte numbers, as well as the levels of C-reactive protein (CRP), by the following formule: IDP = (% neutrophilic granulocytes CRP) / % lymphocytes.
 We have found that, during the inpatient treatment, upon acute clinical manifestations, IDP in study group 1 was increased 12.5 times against the comparison group. It should be noted that all patients were discharged from the hospital in compliance with official criteria, according to Temporary Guidelines. In the study group 2, during early postcovid period, IDP remained 3.4-fold elevated against the comparison group. According to the chest CT data, the patients had signs of a fibrous component, organizing stage of pneumonia and consolidation foci in the lung tissue. Among the group 3 patients (early post-COVID syndrome), IDP was increased three-fold against the comparison group, accompanied by the documented signs of chronic fatigue syndrome and cognitive impairment.
 The IDP can be used as a marker for the prognosis of clinical outcome and a predictor of the evolving complications during the early post-COVID period and upon development of early post-COVID syndrome in the patients who have undergone COVID-19.

Profiles of interferon-gamma and interleukin-2 in patients after allogeneic hematopoietic stem cell transplantation.

BACKGROUNDAllogeneic hematopoietic stem cell transplantation (allo-HSCT) may be related to the occurrence of complications, including graft-versus-host disease (GvHD) and infections. The pathogenesis of acute GvHD is connected with T lymphocytes, which identify alloantigens on host's antigen-presenting cells, activate production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), and act on the immune effector cells and damage tissues and organs.AIMThe aim of the study was to investigate and distinguish serum concentration profiles of IFN-gamma and IL-2 within a 30-d period after allo-HSCT.METHODSWe enrolled 62 patients, i.e., 30 (48%) male and 32 (52%) female subjects [median age 49.5 (19-68) years], after allo-HSCT from siblings (n = 12) or unrelated donors (n = 50) due to acute myeloid leukemia with myeloablative conditioning (n = 26; 42%) and with non-myeloablative conditioning (n = 36; 58%). All patients were given standard immunosuppressive therapy with cyclosporin-A and methotrexate and pre-transplant antithymocyte globulin in the unrelated setting. Blood samples were collected pre-transplant before and after (on day -1) the conditioning therapy and on days +2,+4, +6, +10, +20, and +30 after allo-HSCT. Serum levels of IL-2 and IFN-gamma were determined using ELISA. RESULTSPatients were divided into four groups depending on the presence of acute GvHD and clinical manifestations of infection. Group I included patients with neither acute GvHD nor infections [n = 15 (24%)], group II consisted of patients with infections without acute GvHD [n = 17 (27%)], group III was comprised of patients with acute GvHD without infections [n = 9 (15%)], and group IV included patients with both acute GvHD and infections [n = 21 (34%)]. IFN-gamma concentrations were higher in Group II than in other groups on days +20 (P = 0.014) and +30 (P = 0.008). Post-hoc tests showed lower concentrations of IFN-gamma on day +30 in groups I (P = 0.039) and IV (P = 0.017) compared to group II. The levels of IL-2 were mostly undetectable.CONCLUSIONSerum levels of IFN-gamma following allo-HSCT progressively escalate. High serum levels of IFN-gamma are related to infectious complications rather than acute GvHD. Serum concentrations of IL-2 in most patients are undetectable.