Stress granule-mediated sequestration of EGR1 mRNAs correlates with lomustine-induced cell death prevention.

Some chemotherapy drugs modulate the formation of stress granules (SGs), which are RNA-containing cytoplasmic foci contributing to stress response pathways. How SGs mechanistically contribute to pro-survival or pro-apoptotic functions must be better defined. The chemotherapy drug lomustine promotes SG formation by activating the stress-sensing eIF2α kinase HRI (encoded by the EIF2AK1 gene). Here, we applied a DNA microarray-based transcriptome analysis to determine the genes modulated by lomustine-induced stress and suggest roles for SGs in this process. We found that the expression of the pro-apoptotic EGR1 gene was specifically regulated in cells upon lomustine treatment. The appearance of EGR1-encoding mRNA in SGs correlated with a decrease in EGR1 mRNA translation. Specifically, EGR1 mRNA was sequestered to SGs upon lomustine treatment, probably preventing its ribosome translation and consequently limiting the degree of apoptosis. Our data support the model where SGs can selectively sequester specific mRNAs in a stress-specific manner, modulate their availability for translation, and thus determine the fate of a stressed cell.

Immune profile of children diagnosed with multisystem inflammatory syndrome associated with SARS-CoV-2 infection (MIS-C).

Introduction: The pathophysiology of multisystem inflammatory syndrome associated with SARS-CoV-2 infection (MIS-C) remains poorly understood. This study aimed to define peripheral blood immune features in patients with MIS-C. Material and methods: We analyzed seven children diagnosed with MIS-C between April 1 and May 15, 2021, in St. Joseph's Children's Hospital in Poznan (Poland). Results: All patients had elevated inflammatory markers, IgG antibodies against SARS-CoV-2, and lymphopenia with a marked decrease in CD4+ and CD8+ T cells. The majority of CD4+ T cells were naive cells. Almost all (6/7) of the analyzed patients had a higher CD4+/CD8+ T cell ratio than average values. B cells were within the normal range - the majority were non-memory cells. Conclusions: Children with MIS-C do not resemble adults during COVID-19 recovery. The immune profile of the studied patients differs from that of children with Kawasaki disease (KD), but it is similar to that of adults with severe COVID-19. The proposed explanation is a profound lymphopenia caused by SARS-CoV-2 infection - which persists for weeks - as a result leading to uncontrolled inflammation. In COVID-19 patients the T cell level returns to normal after the second week of the disease. Our data suggest that in children prolonged lymphopenia after COVID-19 can be a practical marker for possible MIS-C alert. If there is a continuum from lymphopenia to MIS-C, there is room for screening and prevention. Further studies are needed to determine whether steroid treatment introduced in a child with prolonged lymphopenia could stop the inflammatory process.

Knowledge among the rural parents about the vaccinations and vaccination coverage of children in the first year of life in Papua New Guinea - analysis of data provided by Christian health services.

Knowledge among the rural parents about the vaccinations and vaccination coverage of children in the first year of life in Papua New Guinea - analysis of data provided by Christian Health Services. BACKGROUND: This analysis aimed to assess rural parents' knowledge about the diseases prevented by vaccinations and establish vaccination coverage in PNG. METHODS: Knowledge of vaccinations was checked through a standard questionnaire (five closed questions). We analyzed data on vaccination coverage from 2016 to 2018 from all Catholic health facilities. Analyzed vaccinations were the pentavalent vaccine (DTaP-HiB-HepB) and measles vaccine given in the first year of life. Coverage was calculated based on the number of vaccines used compared to the number of eligible children. Analyzed vaccinations were the pentavalent vaccine (DTaP-HiB-HepB) and measles vaccine given in the first year of life. RESULTS: Fifty-six parents, including 52 mothers and four fathers, participated in the interview. Many parents (46%) understood that the vaccine prevents diseases. During the analyzed period, 25,502 doses of measles vaccine were given, 31,428 children were vaccinated with the pentavalent vaccine. In 2016, the measles vaccine coverage rate was 26.6 and 33.4% for the pentavalent vaccine. In 2017, measles and pentavalent vaccines' coverage rate was 12.5 and 16.6%, respectively. There were significant differences in immunization coverage between provinces. A decreasing trend in the number of administered vaccinations was observed. CONCLUSION: The results of this analysis demonstrate that in PNG, the majority of children are not fully immunized. There are significant differences in the vaccination coverage between provinces. As protection from diseases is low, there is a very high risk of an outbreak of the vaccine-preventable disease in the community. Delivery of vaccinations in PNG encounters many barriers, from access to healthcare services to natural disasters and inter-tribial conflicts.

SARS-CoV-2 testing and infection control strategies in European paediatric emergency departments during the first wave of the pandemic.

Between February and May 2020, during the first wave of the COVID-19 pandemic, paediatric emergency departments in 12 European countries were prospectively surveyed on their implementation of SARS-CoV-2 disease (COVID-19) testing and infection control strategies. All participating departments (23) implemented standardised case definitions, testing guidelines, early triage and infection control strategies early in the outbreak. Patient testing criteria initially focused on suspect cases and later began to include screening, mainly for hospital admissions. Long turnaround times for test results likely put additional strain on healthcare resources.Conclusion: Shortening turnaround times for SARS-CoV-2 tests should be a priority. Specific paediatric testing criteria are needed. What is Known: • WHO and public health authorities issued case definitions, testing and infection control recommendations for COVID-19 in January. • SARS-CoV-2 testing was made available across Europe in February. What is New: • Paediatric emergency departments implemented COVID-19-specific procedures rapidly, including case definitions, testing guidelines and early triage. • A third of surveyed departments waited more than 24 h for SARS-CoV-2 test to be reported, resulting in additional strain on resources.

Mutation in the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene in a patient with acute lymphoblastic leukemia.

Autoinflammatory syndromes are disorders characterized by recurrent or chronic inflammation caused by the dysregulation of the innate immune system. Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of overactivation of the immune system. We present a case of a 20-month-old boy who was referred to an oncology clinic because of HLH suspicion. In the preceding time, our patient suffered from a severe form of chickenpox with prolonged fever. Tests including myelogram, cerebrospinal fluid, and magnetic resonance (MR) of the brain gave a diagnosis of acute lymphoblastic leukemia from B lymphocyte precursors, without occupying the central nervous system. To exclude inherited HLH in our patient, next-generation sequencing was performed, which revealed a heterozygous missense mutation in exon 15 of the PSTPIP1 gene (c.1213C>T, R405C). No mutations of genes associated with familial HLH syndrome were found. Our patient may be evidence that autoinflammatory diseases caused by PSTPIP1 gene mutations are not limited to the classical pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) phenotype but may have a different clinical presentation, and the spectrum of the PSTPIP1-associated inflammatory diseases (PAID) syndrome is more extensive than previously thought.

The Profile of Microorganisms Responsible for Port-Related Bacteremia in Pediatric Hemato-Oncological Patients.

Patients with pediatric cancer face an increased risk of infections. In most cases, these infections are associated with the use of a long-term central venous catheter. This study describes the epidemiology of a port-associated bacteremia as well as a profile of microorganisms responsible for port-associated bloodstream infections (PABSIs) in pediatric patients with cancer treated in a single center. The retrospective analysis included patients with cancer who had implanted a port, hospitalized between 2010 and 2015 at the Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences. The medical records of patients were reviewed for demographic characteristics, diagnosis, port-related complications, and their management. Data were collected from patients' electronic medical records containing complete information on medical examinations and supplementary tests, diagnosis, timing, and type of port-associated complications. In a study period, 277 ports were inserted to 241 patients. A total of 183 094 catheter days were analyzed. Sixteen patients had more than 1 insertion of a port. The commonest observed complication was PABSI (40.07%) and the incidence density was 0.6 per 1000 port-days. Staphylococcus was the most commonly isolated organisms from patients with PABSI. From all port-associated complications, bloodstream infections and mechanical complications were the most often observed complications. The commonest pathogens responsible for PABSI were coagulase-negative staphylococci. Pathogens resistant to standard antibiotic treatment play an important role in PABSI, with methicillin-resistant Staphylococcus epidermidis being the predominant pathogen. Port-associated bloodstream infections are a common reason for preterm removal of a port.

Genes and their single nucleotide polymorphism involved in innate immune response in central nervous system in bacterial meningitis: review of literature data.

BACKGROUND: There are many studies analysing the effect of SNPs in genes coding proteins which are involved in innate immune response on susceptibility to invasive bacterial disease. Many of them gave inconclusive results. Regarding the complexity of immune response and cooperation between particular elements, number of SNPs may have a cumulative effect on the susceptibility to bacterial meningitis. FINDINGS: In most studies cooccurrence of several SNPs was not analysed. These studies were performed on small groups of patients and usually only few SNPs were checked simultaneously. Additionally, comparison of the results across the studies is hard to conduct. We hypothesise that the number of variants of genes involved in innate immune response plays a role in susceptibility to bacterial meningitis. However, the role of toll-like receptors and other part of innate immune response in the eradication of bacteria, and initiation of the inflammatory response in CNS need further studies. CONCLUSION: Large multicentre studies assessing multiple SNPs in patients with microbiologically proven pneumococcal or meningococcal meningitis are needed to find real genetic risk factors for developing bacterial meningitis. This is necessary to design more effective treatment and prevention strategies for severe infections.

Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still's disease.

A 17-year-old female patient was referred to the Infectious Diseases Ward because of fever lasting for 14 days. On admission to the hospital the patient was in a generally good state, without any abnormalities on physical examination. Laboratory investigation revealed elevated inflammatory markers. Diagnostic imaging comprising chest X-ray, abdominal ultrasonography, and echocardiography showed no abnormalities. During the hospitalization, there occurred episodes of fever with skin rash and musculoskeletal pain of the lower limbs. Procalcitonin concentrations continued to increase. C-reactive protein concentrations decreased during therapy, starting from 191 mg/l. On the 23rd day of the disease, edema of the feet, ankles, and knees appeared. On the basis of the clinical picture and after excluding other possible causes of fever, the patient was diagnosed with adult onset Still's disease. The procalcitonin concentration was normalized after 5 days of steroid therapy. The patient was discharged under ambulatory rheumatologic supervision.

Vaccine-Derived Immunity in Children With Cancer-Analysis of Anti-Tetanus and Anti-Diphtheria Antibodies Changes after Completion of Antineoplastic Therapy.

BACKGROUND: Cancer survival rates and longevity of patients after therapy have significantly improved during the last decades. Thus durable protection against infections should be provided. The aim of the study was to compare the levels of vaccine-derived antibodies in children with cancer compared to those of healthy children and to investigate how therapy influences the levels of specific antibodies. PROCEDURE: A group of 40 children, diagnosed with acute lymphoblastic leukemia (ALL) or solid tumor (ST), followed in Poznan University of Medical Sciences Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, were recruited for evaluation of humoral immunity. Antibody levels were checked before treatment and 3, 6, and 12 months after treatment. RESULTS: In patients with ALL or ST, levels of IgG against tetanus and diphtheria were significantly lower than in the control group. Among ALL patients, 9% remained negative for tetanus and diphtheria antibodies 12 months after therapy. Among patients with ST 3 months after chemotherapy, there were no protective antibodies in 12% against tetanus, and in 18% against diphtheria. All patients reconstituted immunity 6 and 12 months after therapy. CONCLUSIONS: Our data show that a considerable number of cancer patients lose immunity against diphtheria and tetanus after therapy. Compared to ST, patients with ALL lose protective antibody levels more often. Patients with ST reconstituted antibodies after the treatment cessation, while levels in ALL patients remained low.

Pneumocystis pneumonia in children - the relevance of chemoprophylaxis in different groups of immunocompromised and immunocompetent paediatric patients.

INTRODUCTION: Pneumocystis jirovecii is an opportunistic pathogen causing pneumocystis pneumonia (PCP), a life-threatening infection, in immunocompromised patients. In this study, retrospective analysis of the presence of P. jirovecii DNA in different samples collected from children with suspected PCP was carried out. MATERIAL AND METHODS: Three hundred and six specimens [152 bronchoalveolar lavage (BAL) specimens, 80 blood specimens, 18 bronchial secretions (BS), 34 induced sputum samples, 10 endotracheal aspirates (ETA), and 12 other type samples] obtained from patients with suspected PCP were examined by real-time PCR. RESULTS: Forty (13.1%) patients were positive for P. jirovecii: 4 (7.7%) patients with malignancies, 3 (6.8%) transplant recipients, 15 (23.1%) other immunocompromised patients, and 18 (12.4%) immunocompetent patients. Pneumocystis jirovecii DNA was detected in 20.4% of BAL specimens, 11.1% of BS samples, 10% of ETA sample, 8.8% of induced sputum samples, and in 3.7% of blood samples. Comparing the frequency of the presence of P. jirovecii DNA between the group of children treated with PCP chemoprophylaxis (malignancy patients and transplant recipients) and a group of children not receiving this prophylaxis (other immunocompromised and immunocompetent children), we found that the occurrence of PCP was twice as high in the latter group of children (7.3% and 15.7%, respectively). CONCLUSIONS: Respiratory samples, such as BS, BAL, or ETA specimens, are the material of choice for the diagnosis of PCP. Due to high incidence of PCP in certain groups of immunocompetent and immunocompromised patients, besides cancer patients and transplant recipients, consideration of PCP prophylaxis is required in these groups as well.

Management of respiratory tract infections in primary care in Poland--results of the happy audit 2 project.

OBJECTIVE: The Polish results of the international Happy Audit 2 project are reported which objective was to present therapeutic decisions made by general practitioners (especially antibiotics prescribed) and diagnostic methods applied to patients with respiratory tract infections (RTI). MATERIAL AND METHODS: [corrected] Following each visit of patient with respiratory tract infection, general practitioners participating in the study completed the questionnaire. The questionnaire included patient's data (age, gender), the duration of disease, clinical symptoms, diagnosis, prescribed antibiotics, additional testing as well as the influence of various factors on therapeutic decision. RESULTS: Having considered the results of HappyAudit in Poland, a total of 5,137 office visits of patients reporting symptoms of RTIs were analyzed. The average duration of symptoms before visiting GP was 4.8 days (compared to average 4.4 in other countries). Worth noting is that additional testing in diagnosis of RTIs was performed less frequently in Poland: rapid streptococcal test was conducted in 0.4% of cases (European average: 4.45%), CRP--in 2.2% of patients (average from other countries: 14.2%) and chest X-ray in 2.3% of cases compared to 14% in other project's participants. In Poland, the most frequently applied antibiotic was amoxicillin, which was used in 28.9% of cases ended with antibiotic prescribing (amoxicillin/pivampicillin were also predominant in other countries, excluding Sweden). In Poland, macrolides (22.4% of all prescriptions for antibiotic) and cephalosporins (12.1%) were frequently used. The results indicate that narrow-spectrum antibiotics are prescribed in Poland less frequently, with the example being penicillin V which was prescribed in 6.7% of patients with RTIs who were given antibiotic. CONCLUSIONS: Comparing the results of Happy Audit 2 in Poland and other project's participants, the major differences consist in rare use of phenoxymethylpenicillin in favour of amoxicillin and macrolides as well as infrequent use of additional testing in diagnosis of RTIs in Poland.

Detection of drug active ingredients by chemometric processing of solid-state NMR spectrometry data -- the case of acetaminophen.

This paper presents a preliminary study in building discriminant models from solid-state NMR spectrometry data to detect the presence of acetaminophen in over-the-counter pharmaceutical formulations. The dataset, containing 11 spectra of pure substances and 21 spectra of various formulations, was processed by partial least squares discriminant analysis (PLS-DA). The model found coped with the discrimination, and its quality parameters were acceptable. It was found that standard normal variate preprocessing had almost no influence on unsupervised investigation of the dataset. The influence of variable selection with the uninformative variable elimination by PLS method was studied, reducing the dataset from 7601 variables to around 300 informative variables, but not improving the model performance. The results showed the possibility to construct well-working PLS-DA models from such small datasets without a full experimental design.

The Role of Glucocorticoids in the Treatment of Multisystem Inflammatory Syndrome (MIS-C)-Data from POLISH MIS-C Registry.

BACKGROUND: Multisystem inflammatory syndrome (MIS-C) is a condition related to COVID-19. It's most significant feature is cardiac involvement. METHODS: We have analyzed data from 42 hospitals in the Polish MIS-C Registry. To compare the effect of GCS on fever, we formed two groups: the first treated with IVIG and the second treated with IVIG+GCS. RESULTS: There were 111 boys and 56 girls; the mean age was 8.57 years. All the patients were treated with IVIG: 76 patients with IVIG only, and 91 patients with IVIG+GCS. There were no statistically significant differences between the groups regarding age, gender, BMI, or inflammatory markers. Methylprednisolone was the most common drug (80%). Echocardiographic abnormalities on admission were more prevalent in the IVIG+GCS group. Mean time from IVIG infusion to subsidence of fever was 1.1 days, and 1.5 for those in the IVIG+GCS group. CONCLUSIONS: GCS are commonly used in the treatment of MIS-C patients in Poland. Various GCS regimens are used, from a single dose to a month-long therapy. Children with lower lymphocyte levels and cardiac abnormalities on an echocardiographic examination performed on admission were more likely to receive GCS+IVIG. The effect of GCS is difficult to access as patients were not randomly assigned to receive the treatment.

To vaccinate or not to vaccinate - BNT162b2 seroconversion rate and side effects among Polish healthcare workers.

OBJECTIVES: The study aimed to analyze the effect of BNT162b2 vaccination among Polish healthcare workers in terms of serologic response and adverse events. MATERIAL AND METHODS: A questionnaire survey covered data in the period January 1-March 31, 2021 gathered in 2 hospitals in Wielkopolska, Poland. Additionally, serological analysis (SARS-CoV-2 anti-S protein IgG) was performed. RESULTS: A total of 617 medical workers were vaccinated with BNT162b2 (Comirnaty, Pfizer). Data from the questionnaires were received from all of the staff after the first and the second dose. No severe side effects were observed. The most common side effect following the first and second doses of vaccination was pain at the injection site. After the first dose, 3 (1.4 %) women aged 18-55 years, 5 women (3.9 %), and 3 men (8.3 %) aged >55 years had negative SARS-CoV-2 anti-S protein IgG result. After the second dose, all those who agreed to have antibodies tested responded to vaccination with positive SARS-CoV-2 anti-S protein IgG results. CONCLUSIONS: Vaccination tolerance was good in the studied population; no severe side effects were observed. After the second dose, all tested healthcare workers responded to vaccination with antibody production. Int J Occup Med Environ Health. 2022;35(6):761-66.

Clinical characteristics of children with MIS-C fulfilling classification criteria for macrophage activation syndrome.

Background: Macrophage activation syndrome (MAS) is a potentially life-threatening complication of various inflammatory disorders, including multisystem inflammatory syndrome in children (MIS-C). MIS-C refractory to treatment should raise suspicion of MAS, which can be fatal if a definitive diagnosis is delayed. Unfortunately, there is a lack of data on MAS in children with MIS-C. Objective: Our study aims to analyze the risk factors for the development of MAS in MIS-C, its clinical course and response to treatment, and identify predictive factors for pediatric intensive care. Material and methods: We analyzed data from the Polish MIS-C registry of the MultiOrgan Inflammatory Syndromes COVID-19 Related Study. Patients were diagnosed according to the WHO MIS-C definition and treated according to national guidelines (Polish Pediatric Society) based on international consensus. MAS definition was based on 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis. Results: Two-hundred and seventy four children met the study inclusion criteria. Fifty-nine patients fulfilled MAS classification criteria, nine of which required admission to the pediatric intensive care unit (PICU). MIS-C patients with MAS were significantly older than patients without MAS (median 11.2 vs. 8.1 years). Multivariable analysis showed that age, symptoms characteristic of atypical Kawasaki disease, and skin erosions were significant factors associated with MAS in MIS-C patients. Analysis of laboratory parameters showed that on admission, MIS-C patients with MAS had significantly lower median lymphocyte and platelet counts, albumin and sodium levels, and higher median levels of C-reactive protein, procalcitonin, ferritin, D-dimers, triglycerides, serum creatinine, urea, and γ-glutamyl transpeptidase, and neutrophil count. Multivariate analysis showed that higher procalcitonin, ferritin, and fibrinogen levels at admission were predictive of MAS. Only elevated troponin level was a factor indicating a requirement of PICU hospitalization for children with MAS. MIS-C patients fulfilling MAS criteria were treated more often with intravenous immunoglobulins and steroids than children without MAS. Children with MAS more often required mechanical ventilation. None of the patients required biological agents. Conclusions: The clinical course of MAS in MIS-C seems milder, treatment less aggressive, and the prognosis better than expected based on the current knowledge on MAS complicating other rheumatological diseases.

British and Polish general practitioners' opinions on the importance of preventive medicine.

The delivery of preventive services in GPs' surgeries falls below recommended levels. Different attempts are performed to change the situation. The introduction in the UK in 2004 of a new GP contract based on a QOF fundamentally changed the way that primary practitioners are paid. Success of this intervention caused international interest in using financial incentives as a method of improving general practice. Polish primary care is still under development. In contemplating reform and the possible introduction of some of these British solutions in Poland, it would be valuable to compare what British and Polish GPs' think about prevention and see how their opinions can be affected by context in which they work. The aim of the survey involving 65 British and 65 Polish GPs was to compare what are their views of health promotion. The questionnaire solicited information on doctors' demographic characteristics, attitudes toward prevention, time they think they spend on preventive procedures and perceptions of the importance of 13 selected preventive procedures. Most British and Polish GPs answered that prevention is very important and they spend 10-30% of each consultation on it. Almost all doctors rated blood pressure measurement as important. For British GPs BMI, blood glucose, lipid profile, anti-alcohol and anti-smoking advice were important, in contrast to Polish doctors. In the presence of clear clinical guidelines, age and gender do not affect doctors' opinion on the importance of preventive procedures. Procedures in which GPs are directly involved are more important for them.

Can AI Help Pediatricians? Diagnosing Kawasaki Disease Using DRSA.

The DRSA method (dominance-based rough set approach) was used to create decision-making rules based on the results of physical examination and additional laboratory tests in the differential diagnosis of Kawasaki disease (KD), infectious mononucleosis and S. pyogenes pharyngitis in children. The study was conducted retrospectively. The search was based on the ICD-10 (International Classification of Diseases) codes of final diagnosis. Demographic and laboratory data from one Polish hospital (Poznan) were collected. Traditional statistical methods and the DRSA method were applied in data analysis. The algorithm formed 45 decision rules recognizing KD. The rules with the highest sensitivity (number of false negatives equals zero) were based on the presence of conjunctivitis and CRP (C-reactive Protein) ≥ 40.1 mg/L, thrombocytosis and ESR (Erythrocyte Sedimentation Rate) ≥ 77 mm/h; fair general condition and fever ≥ 5 days and rash; fair general condition and fever ≥ 5 days and conjunctivitis; fever ≥ 5 days and rash and CRP ≥ 7.05 mg/L. The DRSA analysis may be helpful in diagnosing KD at an early stage of the disease. It can be used even with a small amount of clinical or laboratory data.

Arterial constriction after resection of neuroblastic tumors in children: Two-center retrospective study.

BACKGROUND/PURPOSE: Neuroblastic tumors are the most common pediatric extracranial solid tumors in infants and very young children. Although, especially in newborns, there is an increasing number of situations in which observation alone is used, surgery remains an important step in the treatment of neuroblastoma but can be complicated by arterial vasospasm in the surgical field. The aim of this two-center retrospective study was to analyze the occurrence of arterial constriction as a complication of neuroblastic tumors resection. METHODS: Medical records of patients who were treated surgically for neuroblastic tumors in the years 2012-2019 were reviewed. RESULTS: For 8 years, 113 children were treated for neuroblastic tumors. The treatment included both primary and delayed surgery after initial chemotherapy carried out according to SIOPEN protocols. In 11 out of 113 cases (9.7%) local arterial constriction was observed. In 6 out of 11 cases an attempt was made to save the organ, however, two patients suffered from kidney atrophy, two other partial kidney infarctions, one child suffered from partial limb paresis, and another from brain ischemia and death. CONCLUSIONS: Local arterial constriction constitutes a relatively common (10% of cases) and severe complication of neuroblastic tumors resection. Efficacy of local application of papaverine based on our experience remains unproven hence further research is warranted.