RAPID IDENTIFICATION OF ETIOLOGICAL AGENTS OF RESPIRATORY TRACT INFECTIONS DURING THE COVID-19 PANDEMIC USING THE MULTIPLEX-PCR METHOD.

Objective. Most respiratory infections have similar symptoms, so it is clinically difficult to determine their etiology. This study aimed to show the importance of molecular diagnostics in identifying the etiological agent of respiratory infections, especially during the coronavirus disease 2019 (COVID-19) pandemic. Methods. A total of 849 samples from patients hospitalized at the University Clinical Center Kragujevac (from January 1 to August 1, 2022) were examined using automated multiplex-polymerase chain reaction (PCR) tests. The BioFire-FilmArray-Respiratory Panel 2.1 test was used for 742 nasopharyngeal swabs [identification of 19 viruses (including SARS-CoV-2) and four bacteria], while the BioFire-FilmArray-Pneumonia Panel was used [identification of 18 bacteria and nine viruses] (BioMerieux, Marcy l'Etoile, France) for 107 tracheal aspirates. The tests were performed according to the manufacturer's instructions, and the results were available within an hour. Results. In 582 (78.4%) samples, the BioFire-FilmArray-Respiratory Panel 2.1 plus test identified at least one pathogen. The rhinovirus (20.6%), SARS-CoV-2 (17.7%), influenza A (17.5%), respiratory syncytial virus (12.4%), and parainfluenza 3 (10.1%) were the most common. Other viruses were found less frequently, and Bordetella parapertussis was detected in one sample. In 85 (79.4%) samples, the BioFire-FilmArray-Pneumonia Panel test identified at least one bacterium or virus. The most prevalent bacteria were Staphylococcus aureus (42.4%), Haemophilus influenzae (41.2%), Streptococcus pneumoniae (36.5%), Moraxella catarrhalis (22.3%), and Legionella pneumophila (2.4%). Among viruses, rhinovirus (36.5%), adenovirus (23.5%), influenza A (11.8%), and the genus Coronavirus (4.7%), were detected. Conclusion. Multiplex-PCR tests improved the implementation of therapeutic and epidemiological measures, preventing the spread of the COVID-19 infection and Legionnaires' disease.Copyright © 2022, Serbian Medical Society. All rights reserved.

COVID-19: comparison lung CT signs and biochemical parameters in the groups of patients with three-time positive RT-PCR and with triple negative RT-PCR test during the period of hospitalization.

Research goal. Comparative characteristics of the dynamics of CT semiotics and biochemical parameters of two groups of patients: with positive RT-PCR and with triple negative RT-PCR. Reflection of the results by comparing them with the data already available in the literature. The aim of the study is to compare the dynamics of CT semiotics and biochemical parameters of blood tests in two groups of patients: with positive RT-PCR and with triple negative RT-PCR. We also reflect the results by comparing them with the data already available in the literature. Materials and methods. We have performed a retrospective analysis of CT images of 66 patients: group I (n1 = 33) consists of patients who had three- time negative RT-PCR (nasopharyngeal swab for SARS-CoV-2 RNA) during hospitalization, and group II (n2 = 33) includes patients with triple positive RT-PCR. An important selection criterion is the presence of three CT examinations (primary, 1st CT and two dynamic examinations - 2nd CT and 3rd CT) and at least two results of biochemistry (C-reactive protein (CRP), fibrinogen, prothrombin time, procalcitonin) performed in a single time interval of +/- 5 days from 1st CT, upon admission, and +/- 5 days from 3st CT. A total of 198 CT examinations of the lungs were analyzed (3 examinations per patient). Results. The average age of patients in the first group was 58 +/- 14.4 years, in the second - 64.9 +/- 15.7 years. The number of days from the moment of illness to the primary CT scan 6.21 +/- 3.74 in group I, 7.0 (5.0-8.0) in group II, until the 2nd CT scan - 12.5 +/- 4, 87 and 12.0 (10.0-15.0), before the 3rd CT scan - 22.0 (19.0-26.0) and 22.0 (16.0-26.0), respectively. In both groups, all 66 patients (100%), the primary study identified the double-sided ground-glass opacity symptom and 36 of 66 (55%) patients showed consolidation of the lung tissue. Later on, a first follow-up CT defined GGO not in all the cases: it was presented in 22 of 33 (67%) patients with negative RT-PCR (group I) and in 28 of 33 (85%) patients with the positive one (group II). The percentage of studies showing consolidation increased significantly: up to 30 of 33 (91%) patients in group I, and up to 32 of 33 (97%) patients in group II. For the first time, radiological symptoms of "involutional changes" appeared: in 17 (52%) patients of the first group and in 5 (15%) patients of the second one. On second follow-up CT, GGO and consolidations were detected less often than on previous CT: in 1 and 27 patients of group I (3% and 82%, respectively) and in 6 and 30 patients of group II (18% and 91%, respectively), although the consolidation symptom still prevailed significantly . The peak of "involutional changes" occurred on last CT: 31 (94%) and 25 (76%) patients of groups I and II, respectively.So, in the groups studied, the dynamics of changes in lung CT were almost equal. After analyzing the biochemistry parameters, we found out that CRP significantly decreased in 93% of patients (p < 0.001) in group I;in group II, there was a statistically significant decrease in the values of C-reactive protein in 81% of patients (p = 0.005). With an increase in CT severity of coronavirus infection by one degree, an increase in CRP by 41.8 mg/ml should be expected. In group I, a statistically significant (p = 0.001) decrease in fibrinogen was recorded in 77% of patients;and a similar dynamic of this indicator was observed in group II: fibrinogen values decreased in 66% of patients (p = 0.002). Such parameters as procalcitonin and prothrombin time did not significantly change during inpatient treatment of the patients of the studied groups (p = 0.879 and p = 0.135), which may indicate that it is inappropriate to use these parameters in assessing dynamics of patients with a similar course of the disease. When comparing the outcomes of the studied groups, there was a statistically significant higher mortality in group II - 30.3%, in group I - 21.2% (p = 0.043). Conclusion. According to our data, a course of the disease does not significantly differ in the groups o patients with positive RT-PCR and three-time negative RT-PCR. A negative RT-PCR analysis may be associated with an individual peculiarity of a patient such as a low viral load of SARS-CoV-2 in the upper respiratory tract. Therefore, with repeated negative results on the RNA of the virus in the oro- and nasopharynx, one should take into account the clinic, the X-ray picture and biochemical indicators in dynamics and not be afraid to make a diagnosis of COVID-19.Copyright © 2021 ALIES. All rights reserved.

A Case of X-Linked Moesin-Associated Immune Deficiency in a Pediatric Patient

Background: X-Linked Moesin-Associated Immune Deficiency (X-MAID) is a rare severe combined immunodeficiency (SCID) subtype that can present at any age due to its variability. Depending on severity, patients demonstrate failure to thrive, recurrent bacterial and viral infections, and increased susceptibility to varicella zoster. It has been characterized by marked lymphopenia with hypogammaglobulinemia and impaired T-cell migration and proliferation. Case Presentation: This is a report of a Cuban 7-year-old male with poor weight gain and facial dysmorphia. He had a history of recurrent bacterial gastrointestinal infections and pneumonia beginning at 4 months of age. He additionally had 4-6 upper respiratory tract and ear infections annually. While still living in Cuba, he was admitted for a profound EBV infection in the setting of significant leukopenia. A bone marrow biopsy confirmed no malignancy. After he moved to the United States, his laboratory work-up revealed marked leukopenia with low absolute neutrophil and lymphocyte count with low T and B cells, very low immunoglobulin levels IgG, IgA, and IgM, and poor vaccination responses to streptococcus pneumonia, varicella zoster, and SARS-CoV-2. Genetic testing revealed a missense pathogenic variant c.511C>T (p.Arg171Trp) in the moesin (MSN) gene associated with X-MAID. He was managed with Bactrim and acyclovir prophylaxis, and immunoglobulin replacement therapy, and considered for hematopoietic stem cell transplantation. Discussion(s): Diagnosis of X-MAID should be considered in patients with recurrent infections and profound lymphopenia. As with SCID, early diagnosis and intervention is of utmost importance to prevent morbidity and mortality. This case demonstrates the importance of genetic testing in identifying this disease as it may prompt an immunologist to consider HSCT if conservative management is suboptimal. In the current literature, HSCT appears promising, but the long-term outcomes have yet to be described.Copyright © 2023 Elsevier Inc.

Could platelet mass index (PMI) be a new prognostic biomarker for COVID-19?

Aim: Although most patients with COVID-19 experience respiratory tract infections, severe reactions to the virus may cause coagulation abnormalities that mimic other systemic coagulopathies associated with severe infections, such as disseminated intravascular coagulation and thrombotic microangiopathy. Fluctuations in platelet markers, which are an indicator of the acute phase response for COVID-19, are of clinical importance. The aim of this study is to evaluate the relationship between disease severity and Platelet Mass Index (MPI) parameters in COVID-19 patients. Material(s) and Method(s): This retrospective observational study was conducted with patients who were diagnosed with COVID-19 in a tertiary hospital. The study was continued with the remaining 280 patients. All laboratory data were scanned retrospectively from patient files and hospital information system. Result(s): A very high positive correlation was found between PMI and PLT. The PMI value in women was significantly higher than in men. It was observed that PMI did not differ significantly in terms of mortality, intubation, CPAP and comorbidity. PMI vs. Pneumonia Ct Severity Score, biochemistry parameters (AST, CRP), hemogram parameters (WBC, HGB, HCT, MCV, LYM, MPV EO) and coagulation factors (aPTT and FIB) at various levels of positive/negative, weak and strong, and significant relationship was found. There was no significant relationship between hormone and D-dimer when compared with PMI. Discussion(s): Although platelet count alone does not provide information about the prognosis of the disease, PMI may guide the clinician as an indicator of lung damage in seriously ill patients.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Fulminant varicella infection complicated by disseminated intravascular coagulation following influenza-A case report

Objectives: Varicella is common infectious disease mainly in childhood, usually is a mild, self-limited illness and complications are usually rare. The incubation period for this disease is generally 14- 16 days but may vary from 7 to 21 days. Varicella in the adults with comorbidities or immunosuppressed children may be severe and prolonged with complications. Method(s): A case report of a 6-year-old girl hospitalized for new-onset manifestations of disseminated vesicular exanthema, the manifestations of which occurred mainly on the chest, back, capillitium, oral cavity, and genital area. The child was suffering from abdominal, knee and lumbosacral pain at that time. The patient's history revealed that 10 days prior to the cutaneous manifestations, she had influenza with bronchopneumonia requiring oxygen therapy, steroids and antibiotics. Result(s): The condition progressed within 48 h, complicated by the development of multi-organ failure, coagulopathy with the development of disseminated intravascular coagulopathy over the course of antiviral, antibiotic and antifungal therapy. Laboratory parameters included high elevation of C-reactive protein, il-6, leukocytosis, neutrophilia and highly elevated liver enzymes. Varicella infection was confirmed by detection of herpes zoster virus - polymerase chain reaction (PCR) from vesicles. The patient received intravenous immunoglobulin therapy at a dose of 2 g/L and fresh frozen plasma, thrombocyte concentrate. The girl was intubated with analogization. Laboratory parameters subsequently revealed high anti CoV-2 positivity, high CoV-2 IgG positivity and negative CoV-2 IgM. The patient's condition did not preclude the course of multisystem inflammatory syndrome in children (MIS-C) corticosteroids were added to the treatment at a dose of 1 mg/kg weight. Patient's condition stabilized after 1 month. Discussion(s): Our case report presents an example of fulminant complicated life-threatening course of varicella. Even in common respiratory infections, we must think about the risk and consequences of coinfections and post-infectious complications such as in our case especially influenza and COVID-19.

Ethnic, racial and migrant inequalities in respiratory health

Disparities in the incidence, prevalence, and morbidity and mortality rates of many respiratory diseases are evident among ethnic groups. Biological, cultural and environmental factors related to ethnicity can all contribute to the differences in respiratory health observed among ethnic minority groups, but the inequalities observed are most commonly due to lower socioeconomic position. People who migrate within a country or across an international border may experience an improvement in respiratory health associated with improvements in socioeconomic position. However, migrants may also experience worse health outcomes in destination countries, as they are faced by barriers in language and culture, discrimination, exclusion and limited access to health services. While some high-quality studies investigating ethnicity and respiratory health are available, further research into ethnic differences is needed. Improving the recording of ethnicity in health records, addressing barriers to accessing respiratory healthcare and improving cultural literacy more generally are some of the ways that inequalities can be tackled.Copyright © ERS 2023.

Housing and respiratory health: Exposures, health effects and interventions

Housing quality and affordability are well established as social determinants of health through direct and indirect mechanisms. Respiratory illnesses related to housing are nearly all the result of housing disrepair that allows intrusion into the home of environmental agents that are directly or indirectly associated with disease. Structural deficiencies such as leaks, cracks in the foundation or holes in the home's exterior can facilitate the presence of mould, which is causally linked to the development of asthma and is associated with exacerbation of asthma symptoms in children and adults. Indoor cleanliness can also contribute to the presence of mice and cockroaches. Proper ventilation can improve air quality, reducing exposure to PM, VOCs and infectious respiratory agents. Disparities in exposure to the housing conditions associated with respiratory disease are readily apparent across socioeconomic lines. Low-income families are less likely to be able to afford the costs of maintaining a home, which prevents them from making repairs that could improve respiratory health.Copyright © ERS 2023.

Teclistamab in combination with daratumumab and lenalidomide in multiple myeloma (MajesTEC-2 study)

Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.

Physical and mental condition and medicine consumption of frontline medical staff of shelter hospitals in Shanghai during the fight against the epidemic of coronavirus disease 2019.

Objective To investigate the physical and mental condition and medicine consumption of medical staff of shelter hospitals in Shanghai during the fight against the epidemic of coronavirus disease 2019 (COVID-19). Methods A total of 144 frontline medical staff who fighting against the COVID-19 epidemic from a tertiary first-class hospital from Apr. 4 to May 12, 2022 were surveyed by questionnaires online. Their physical condition including body weight change before the medical work and one month later, sleep quality and the medicine consumption during the medical work were collected and analyzed. Results The mean body weight of frontline doctors before the medical work and one month later were (69.80+/-8.35) kg and (68.60+/-7.37) kg, while those of nurses were (55.36+/-8.27) kg and (53.80+/-7.38) kg, both showing a decreasing trend but without significant difference (all P0.05). A total of 63.89% (92/144) frontline medical staff suffered from insomnia, of which 27.08% (39/144) needed drug intervention. The top 5 common diseases among frontline medical staff were sleep disorder (63.89%, 92/144), skin injury (25.69%, 37/144), body pain (23.61%, 34/144), oral ulcer (13.19%, 19/144), and acute upper respiratory tract infection (9.72%, 14/144). A total of 155 medical staff used drugs, and the top 5 common drugs were skin application (16.77%, 26/155), Ganmao'an granule (12.26%, 19/155), zolpidem tartrate tablets (11.61%, 18/155), Kangfuxin liquid (11.61%, 18/155), and celecoxib capsules (8.39%, 13/155). Conclusion Frontline medical staff in shelter hospitals are prone to have body weight change, sleep disorder, skin injury, body pain, oral ulcer, acute upper respiratory tract infection and so on, which suggests that in future similar large-scale medical support, it is necessary to pay sufficient attention to the physical condition of frontline medical staff and provide them sufficient medicine.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Boosting the Immune System with Vitamin D: Special Focus on Prevention of COVID-19 and Complications

In addition to the classical functions of the musculoskeletal system and calcium homeostasis, the function of vitamin D as an immune modulator is well established. The vitamin D receptors and enzymes that metabolize vitamin D are ubiquitously expressed in most cells in the body, including T and B lymphocytes, antigen-presenting cells, monocytes, macrophages and natural killer cells that trigger immune and antimicrobial responses. Many in vitro and in vivo studies revealed that vitamin D promotes tolerogenic immunological action and immune modulation. Vitamin D adequacy positively influences the expression and release of antimicrobial peptides, such as cathelicidin, defensin, and anti-inflammatory cytokines, and reduces the expression of proinflammatory cytokines. Evidence suggestss that vitamin D's protective immunogenic actions reduce the risk, complications, and death from COVID-19. On the contrary, vitamin D deficiency worsened the clinical outcomes of viral respiratory diseases and the COVID-19-related cytokine storm, acute respiratory distress syndrome, and death. The study revealed the need for more preclinical studies and focused on well-designed clinical trials with adequate sizes to understand the role of vitamin D on the pathophysiology of immune disorders and mechanisms of subduing microbial infections, including COVID-19.Copyright © 2023 Bentham Science Publishers.

Should Young Covid-19 Patients be Suplemented with Vitamin D?

It is well known that vitamin D's general immunomodulatory actions are helpful in viral infections and that a shortage is linked to a more serious prognosis for Covid-19. In this sistematic review, we examined the existing literature on evidence as to whether there is also link between vitamin D range levels in pediatric population and the outcome of the Covid-19 infection. We looked for studies that measured vitamin D blood concentrations and examined the effects of vitamin D supplementation in young infected patients. Vitamin D may decrease the risk of respiratory infections in a number of ways through its interactions with numerous cells, including by decreasing viral survival and replication, reducing the cytokine storm, raising angiotensin-converting enzyme 2 concentrations (ACE2) while not damaging the endothelial integrity. The incidence or severity of Covid-19 is linked with blood 25-hydroxyvitamin D concentrations, according to many observational studies. However experimental verification is still needed. Given their safety and broad therapeutic window, vitamin D supplements seem to be an effective way for individuals and doctors to prevent or treat Covid-19. Nonetheless, the outcomes of significant vitamin D randomized controlled trials are further needed.Copyright © 2022 Maria Nicolae et al., published by Sciendo.

The influence of the Covid-19 pandemic on the shunt revision rate

Introduction: During the first year of the Covid-19 pandemic we observed a decrease of our shunt revision rate. In order to investigate a possible correlation with an assumingly lower general infection rate in children in times of lock down and homeschooling, we performed a detailed analysis of our shunt and general pediatric patient population. Method(s): Electronic patient charts retrieval for children admitted for shunt revision or infectious diseases was performed for four time periods (study period April 2020 - March 2021, control periods from three previous years). A detailed analysis of all shunt revision and infectious cases including age and season specific evaluation followed. Possible correlations were investigated. Result(s): A total of 318 shunt revision and 13,919 pediatric cases have been evaluated. The shunt revision rate during the study period was 29% less compared to the average rate of three previous years (p 0.061), the number of pediatric cases with main diagnosis infection dropped significantly (p < 0.05), whereas other pediatric admissions remained stable. Significant age or seasonal influences did not exist. The number of shunt revisions in association with a documented systemic infection or a primary shunt infection dropped significantly during the study period (p<0.05 each). This was not the case for underdrainage, overdrainage (p>0.05 each) or other indications. In general, infections of upper and lower airways, the gastrointestinal and nervous system decreased during the pandemic, urinary infection rates remained stable. Conclusion(s): The decreased shunt revision rate during the first year of the pandemic seems correlate with a decrease of the general infection rate in children and adolescents at the same time. Infectionassociated shunt failures showed a significant decrease during this period compared to previous years.

Potential targets and traditional Chinese medicine treatment strategy of cough after SARS-CoV-2 infection.

The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) Omicron variants BA.5.2 and BF.7 have become the main epidemic strains in China since the quarantine policy was lifted in 7th December 2022. Cough is one of the main symptoms induced by SARS-CoV-2 infection. SARS-CoV-2 infection-associated cough injuries the lung and upper respiratory tract, while the infected people cough out virus and liquid which forms virus-containing aerosols, a medium for quickly spreading. Furthermore, cough is one of primary sequelae of discharged patients in corona virus disease 2019 (COVID-19). By now, there are no efficacious drugs for treatment of upper respiratory tract infection associated cough induced by omicron. Traditional Chinese medicine (TCM) has a long history on treating cough. By reviewing the mechanisms of the occurrence of cough after SARS-CoV-2 infection, potential therapeutic targets and cough suppressant herbs with significant efficacy in clinical and basic research, we provide a reference for the treatment of cough after SARS-Cov-2 infection and a basis for the majority of infected patients to select appropriate herbs for cough relief under guidance of physicians.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Unexpected Severe Bocavirus Infections among Hospitalized Children during the COVID-19 Pandemic

Objective: Acute respiratory tract infections are one of the leading causes of morbidity and mortality in children. Although human bocavirus (HBoV) infections are not as common as other seasonal respiratory viruses, children who are infected with HBoV are more likely to suffer from a variety of respiratory conditions, including the common cold, acute otitis media, asthma exacerbations, bronchiolitis pneumonia, some of the affected children require pediatric intensive care unit stay. Here, we aimed to evaluate pediatric bocavirus (HBoV) cases presenting with severe respiratory tract symptoms during the coronavirus disease 2019 (COVID-19) pandemic. Method(s): This retrospective study evaluated the medical records of children diagnosed with respiratory infections, followed up at the Faculty of Medicine, Eskisehir Osmangazi University between September 2021 and March 2022. In this study, patients with HBoV identified using nasopharyngeal polymerase chain reaction (PCR) were considered positive. Cases were analyzed retrospectively for their clinical characteristics. Result(s): This study included 54 children (29 girls and 25 boys) with HBoV in nasopharyngeal PCR samples. The cases ranged in age from 1 month to 72 months (median 25 months). At the time of presentation, cough, fever, and respiratory distress were the most prevalent symptoms. Hyperinflation (48%), pneumonic consolidation (42%), and pneumothorax-pneumomediastinum (7%) were observed on the chest X-ray;54% of the children required intensive care unit stay. The median length of hospitalization was 6 days. Bacterial coinfection was detected in 7 (17%) children, while HBoV and other viruses were present in 20 (37%) children;57% of children received supplemental oxygen by mask, 24% high-flow nasal oxygen, 7% continuous positive airway pressure, and 9% invasive mechanical ventilation support. Antibiotics were given to 34 (63%) cases, and systemic steroid treatment was given to 41 (76%) cases. Chest tubes were inserted in three out of the four cases with pneumothorax-pneumomediastinum. All patients were recovered and were discharged from the hospital. Conclusion(s): The COVID-19 pandemic changed the epidemiology of seasonal respiratory viruses and the clinical course of the diseases. Although it usually causes mild symptoms, severe respiratory symptoms can lead to life-threatening illnesses requiring intensive care admission.Copyright © 2023. The Author(s).

New definition of RIME: Mucocutaneous eruptions, bullous lesions and multi-mucosal involvement

Objectives: A 14-year-old female patient presents with marked haemorrhagic, adherent crusting of the upper and lower lip and enoral vesicles and erosions. Two weeks before, she had suffered from a respiratory tract infection. She did not take antibiotics but ibuprofen. One week later, she described a swelling and crusting of the upper and lower lips. Urogenital mucosa was also erosive. There was no ocular involvement. Another week later, cocard-like single lesions with partly central blister formation developed. A flaccid blister of 15 mm in diameter was detected in the left ear helix. In total, there was a limited cutaneous involvement of <10% BSA. The girl was admitted to the paediatric clinic. Method(s): Due to mucocutaneous eruptions, bullous lesions and multimucosal involvement, we assumed a Steven-Johnson syndrome or reactive infectious mucocutaneous eruption (RIME). Intravenous rehydration and prophylactic administration of cefotaxime and aciclovir were given. She was balanced and given analgesia with novalgin. The recent increased intake of ibuprofen was discontinued. Local therapy included mometasone cream and serasept dressings. During the inpatient stay, the general condition stabilised and the skin efflorescence's showed a clear regression. Result(s): The microbiological smears for COVID-19, HSV, VZV, mycoplasma, and chlamydia were negative. Discussion(s): As adult classifications for blistering severe cutaneous adverse reactions are limited applicable in children, Ramien et al. proposed revised paediatric-focused clinical criteria 2021. They leave traditional definitions of EEM, SJS and TEN. But they distinguish erythema multiforme (EM) for classic targets with/without mucosal involvement, RIME for cases with mucosal predominance and a respiratory infection trigger, and drug-induced epidermal necrolysis (DEN) for cases caused by medications. (Ramien BJD 2021) There are no current guidelines for RIME therapy. A reasonable management approach includes symptomatic therapy, treatment of identifiable infectious triggers (if possible), consulting urologists, ophthalmologists and gynaecologists (if necessary), immunosuppression, and psychological support. (Ramien ClinExpDermatol 2021).

Real world experience of the burden of infection in myeloma

The treatment landscape in myeloma has rapidly changed over the last few years with the advent of an ever increasing number of funded novel therapies. At the same time, the COVID-19 pandemic has caused a paradigm shift in the burden of infection within the community. Clinical trials often exclude older and more comorbid patients and so there is a paucity of data of the effect of infection on patients with myeloma in the 'real world'. We performed a restrospective audit of all patients with myeloma admitted with infection to our level 2b haematology centre over a 3-year period from November 2019 to November 2022. We collected data on patient demographics and characteristics, infection status, microbiology results, length of stay and outcome of admission. During the audit period there were 87 admissions from 52 patients. The median number of admissions per patient was 1 (range 1-6). The median age at admission was 72 (range 41-90). Patients had a median of two major comorbidities (range 0-8). Performance status was <2 in 63% of patients (33/52). In terms of disease characteristics, International Staging Score (ISS) was stage 1 in 12% of patients, stage 2 in 38%, stage 3 in 38% and unavailable in 12%. Revised ISS (R-ISS) was stage 1 in 2% of patients, stage 2 in 44%, stage 3 in 17% and unavailable in 37%. The median line of treatment was 2 (range 0-6). Respiratory tract infection was the most common site of infection in 51% of admissions. Microbiology was negative in over half of infection admissions (50/87). Fifteen per cent (13/87) had a positive COVID-19 PCR. A positive blood culture result was identified in 8% (7/87). The median length of stay was 9 days (range 1-58). The mortality rate of admissions with infection was 17% (15/87). Overall, our real-world results show the continuing burden of infection in myeloma in the era of modern treatment. Despite the omnipresence of the COVID-19 pandemic over the last 2 and a half years, this contributed to only a small number of admissions. Infections happened in patients of all ages and many patients had good performance status, limited comorbidities and intermediate risk disease. The mortality rate of our cohort was surprisingly high at 17%. In summary, infection remains a major complication of myeloma. Given our results we now plan a trial of prophylactic antibiotics for patients on active treatment.

Development of warm autoimmune hemolytic anemia after initiation of Ruxolitinib in a patient with STAT1 gain-of-function mutation

Introduction: STAT1 gain-of-function (GOF) disease is associated with chronic mucocutaneous candidiasis (CMC) and a broad spectrum of infectious, inflammatory, and vascular manifestations. The Janus Kinase inhibitor ruxolitinib has been used successfully for CMC and autoimmune phenomena. We describe a case of warm autoimmune hemolytic anemia (WAIHA) in a patient with STAT1 GOF disease after initiating ruxolitinib. Case report: A 36-year-old man with STAT1 c.850G>A (p.Glu284Lys) mutation presented with CMC as well as recurrent viral and bacterial infections, lymphadenopathy, enteritis, nodular regenerative hyperplasia (NRH) and splenomegaly. Immune workup confirmed a combined immunodeficiency with hypogammaglobulinemia and T-cell lymphopenia. Ruxolitinib was initiated at 5 mg twice daily (due to pre-existing thrombocytopenia) with up titration over 3 months to 20 mg twice daily. He improved with weight gain, increased energy, resolution of chronic anemia, and improved lymphadenopathy and splenomegaly on imaging. Serum CXCL9 only minimally decreased from 4660 pg/ml to 3990 pg/ml. Soon after reaching ruxolitinib 20 mg twice daily, he developed JC viremia, prompting dose reduction to 15 mg BID. Within two weeks, he developed a non-COVID upper respiratory tract infection followed by fatigue, shortness of breath with ambulation, and dark urine. Emergency evaluation revealed warm antibody positive hemolytic anemia with a hemoglobin of 5 g/dL, and worsened thrombocytopenia. He was treated with blood transfusions, pulse steroids, and high-dose IVIG with stabilization but continued hemolysis. Due to the JC viremia, there was concern to give rituximab with increased PML risk. Bone marrow showed trilineage hematopoiesis, a mild increase in megakaryocytes and RBC precursors, and a loss of B-cell progenitors with retention of mature B cells. His B and T lymphocyte numbers had increased since prior to ruxolitinib, with a predominance of Tfh1-cells (58.7% of total Tfh-cells). He was started on sirolimus with a slow taper of prednisone with continued stable hemoglobin and platelets, and resolution of hemolysis after 3 months. Conclusion(s): To our knowledge, this is the first case of a STAT1 GOF patient developing WAIHA while receiving ruxolitinib therapy. Treatment choices were complicated by the risks of PML. Sirolimus combined with ruxolitinib allowed wean of corticosteroid and subsequent resolution of hemolysis.Copyright © 2023 Elsevier Inc.

Systematic computer analysis of the pharmacology of bioflavonoids in the context of increasing the body's antiviral defenses.

Background. The rapidly developing resistance of viruses to synthetic antiviral drugs indicates the need to use substances with multitarget action (to avoid polypharmacy and to improve the safety of treatment). Objective(s): systematic analysis of the scientific literature on the pharmacology of bioflavonoids with an emphasis on their antiviral action. Material and methods. More than 150,000 references of primary sources were found in the PubMed/MEDLINE database of biomedical publications, including 3282 references on the antiviral effects of bioflavonoids. A systematic computerized analysis of this array of publications was carried out in order to identify the main directions in the pharmacology of bioflavonoids with an emphasis on their antiviral, antibacterial and immunomodulatory effects. The literature analysis was carried out using modern methods of topological and metric analysis of big data. Results. The molecular mechanisms of action of baicalin, hesperidin, rutin, quercetin, leukodelphinidin bioflavonoids and epigallocatechin-3gallate, curcumin polyphenols, their anti-inflammatory, antioxidant, antiviral, bactericidal, angioprotective, regenerative effects, and their prospects in therapy, prevention and rehabilitation of patients with COVID-19 and other respiratory viral infections were described in detail. Conclusion. Bioflavonoids and synergistic polyphenols exhibit not only multitarget antiviral effects by inhibiting the main protease, spike proteins, and other target proteins, but also pronounced anti-inflammatory, hepatoprotective, and immunomodulatory effects.Copyright © 2023 Modern Medical Technology. All rights reserved.

Respiratory syncytial virus: desperately seeking solutions

Respiratory syncytial virus (RSV) infection remains a major public health problem, especially in younger children and the elderly. But several monoclonal antibodies, antivirals and vaccines, either recently launched or in development, offer new hope for RSV prevention and treatment.Copyright © 2023 Wiley Interface Ltd.

Stem cells used in infectious diseases like pneumonia, respiratory infections and Covid-19: A study based on doctor's opinion

Worldwide, infectious diseases have contributed significantly to morbidity and mortality;among the leading causes of death are pneumonia, respiratory infections and Covid-19. Stem cell therapy will be used to treat virus-infected patients in an effective and safe manner. A cross-sectional questionnaire was used to collect data from doctors. Most doctors are aware of the applications of stem cells, but they do not confirm their usage because clinical trials are ongoing. Instead, they show support for using stem cells to treat patients. Stem cells have been hoping to help repair damaged tissues in the respiratory system to promote faster recovery. Stem Cells are being studied in current clinical trials for their efficacy and safety in virus severe pneumonia and respiratory infections. The doctors suggested that stem cells have been used in infectious diseases to improve their health.Copyright © 2023 Health Biotechnology And Biopharma. All rights reserved.