Frequency Of Infections Research Articles

Frequency of urinary infections related to urinary catheter use in the intensive care unit

Uvod: Kateterizacija je rutinski postupak kojim se omogućava drenaža urina iz mokraćnog sustava. Komplikacija vezana za kateterizaciju jest infekcija mokraćnog sustava koja uzrokuje značajan morbiditet. Cilj: Cilj je rada utvrditi učestalost urinarnih infekcija povezanih s upotrebom urinarnih katetera kod pacijenata koji su hospitalizirani u jedinici intenzivnog liječenja (JIL) tijekom 2009. i 2018. godine, koristeći se protokolom iz 2005. godine prema kojem se urinarni kateter mijenjao svaka dva tjedna i iz 2015. godine prema kojem se mijenjao svaka tri tjedna. Ispitanici i metode: U istraživanje su uključeni pacijenti koji su bili hospitalizirani u JIL-u Opće bolnice Šibensko-kninske županije od 1. 1. do 31. 12. 2009. godine i od 1. 1. do 31. 12. 2018. godine. Ukupan broj liječenih tijekom te dvije godine čini 761 pacijent, od kojih je 386 pacijenata liječeno u 2009. godini i 375 pacijenata u 2018. godini. Rezultati: Tijekom 2009. godine, od ukupno 386 pacijenata, uzorkovano je njih 114 (29,5 %), a od ukupno 375 pacijenata u 2018. godini, uzorkovano je 77 (20,5 %) pacijenata. Pacijenata s nesterilnim nalazom urinokulture značajno je više tijekom 2009. godine, njih 60 (52,6 %) (χ 2 test, P = 0,02), u odnosu na broj pacijenata s nesterilnim nalazom iz 2018. godine, njih 27 (35,1 %). Međutim, nema značajne razlike u nalazima u odnosu na promatrane godine. Zaključak: Primjena protokola kod pacijenata s urinarnim kateterom koji su liječeni u JIL-u nije imala statistički značajnu razliku na učestalost urinarnih infekcija u uspoređivanim godinama.

Prevalence and Risk Factors of Parasitic Gastrointestinal Nematode Infections of Donkeys in Southern Ethiopia

Gastrointestinal (GIT) parasites cause sickness and mortality in working donkeys, reducing their productivity. A cross-sectional study was done in the Damot Gale district of southern Ethiopia from November 2020 to June 2021 to determine the frequency of donkey GIT nematode parasite infection and to examine its related risk factors. Overall, 514 simple randomly selected donkeys from peasant associations were sampled for the coprological examination of gastrointestinal nematode infection. The flotation technique was employed to identify parasite eggs in feces. The total prevalence of parasitic gastrointestinal nematodes was 71.79% (95% CI: 67.73-75.52). The most prevalent nematodes were Strongyles (37.74%), Parascaris equorum (11.28%), Strongyloides (7.20%), and combined infections of Strongyles and Parascaris (14.01%) and Strongyles and Strongyloides (1.56%). The association between the prevalence of parasitic GIT nematode infections and body conditions score was statistically significant (p<0.05). Comparatively, donkeys with semi-intensified systems were five times (OR=5.36) and those with medium body condition were twice (OR=1.94) had a higher risk of infection than donkeys with intensive systems and good body condition scores, respectively. In conclusion, the current study indicated that gastrointestinal nematode parasites of donkeys are highly prevalent in the study area. Thus, regular deworming, proper housing, and feeding management were recommended to improve the health and productivity of donkeys in the research area.

Cutting Edge: First Lung Infection Permanently Enlarges Lymph Nodes and Enhances New T Cell Responses.

Humans experience frequent respiratory infections. Immunology and vaccinology studies in mice are typically performed in naive specific pathogen-free animals responding to their very first respiratory challenge. We found that the first respiratory infection induces lifelong enlargement of the lung-draining mediastinal lymph nodes (medLNs). Furthermore, infection-experienced medLNs supported better naive T cell surveillance and effector responses to new unrelated infections that exhibited more biased accumulation and memory establishment within the lung. Moreover, we observed that weight loss induced by influenza infection was substantially reduced in mice that had recovered from a previous unrelated respiratory viral challenge. These data show that the lack of infectious history and corresponding medLN hypoplasia in specific pathogen-free mice alter their immune response to lung infections. Preclinical vaccination and immunology studies should consider the previous infectious experience of the model organism.

Birmekizumab: Erweitert die Therapieoptionen besonders bei axialer Spondylarthritis

<b>Objectives:</b> Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) at Week 16. Here, the objective is to report the efficacy and safety of BKZ at Week 52. <b>Methods:</b> BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) comprised a 16-week, double-blind, placebo-controlled period, then a 36-week maintenance period. From Week 16, all patients received subcutaneous BKZ 160 mg every 4 weeks. <b>Results:</b> Improvements versus placebo in Assessment of SpondyloArthritis International Society ≥40% response (primary endpoint), Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels and MRI inflammation of the sacroiliac joints/spine at Week 16 were sustained to Week 52 in BKZ-randomised patients. At Week 52, responses of patients switching from placebo to BKZ at Week 16 were comparable to BKZ-randomised patients. At Week 52, ≥1 treatment-emergent adverse events (TEAEs) were reported in 183 (75.0%) and 249 (75.5%) patients with nr-axSpA and r-axSpA, respectively. Serious TEAEs occurred in 9 (3.7%) patients with nr-axSpA and 20 (6.1%) patients with r-axSpA. Oral candidiasis was the most frequent fungal infection (nr-axSpA: 18 (7.4%); r-axSpA: 20 (6.1%)). Uveitis occurred in three (1.2%) and seven (2.1%) patients with nr-axSpA and r-axSpA, and inflammatory bowel disease in two (0.8%) and three (0.9%).

SARS-CoV-2 Test-to-Stay in Daycare.

Test-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess the safety of a test-to-stay screening in daycare facilities. 714 daycare facilities and approximately 50 000 children ≤6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-polymerase chain reaction (PCR) screening from March 2021 to April 2022. The screening initially comprised post-exposure quarantine and was adapted to a test-to-stay approach during its course. To assess safety of the test-to-stay approach, we explored potential changes in frequencies of infections among children after the adaptation to the test-to-stay approach by applying regression discontinuity in time (RDiT) analyses. To this end, PCR-test data were linked with routinely collected data on reported infections in children and analyzed using ordinary least squares regressions. 219 885 Pool-PCRs and 352 305 Single-PCRs were performed. 6440 (2.93%) Pool-PCRs tested positive, and 17 208 infections in children were reported. We estimated that during a period of 30 weeks, the test-to-stay concept avoided between 7 and 20 days of quarantine per eligible daycare child. RDiT revealed a 26% reduction (Exp. Coef: 0.74, confidence interval 0.52-1.06) in infection frequency among children and indicated no significant increase attributable to the test-to-stay approach. This result was not sensitive to adjustments for 7-day incidence, season, SARS-CoV-2 variant, and socioeconomic status. Our analyses provide evidence that suggest safety of the test-to-stay approach compared with quarantine measures. This approach offers a promising option to avoid use of quarantine after exposure to respiratory pathogens in daycare settings.

Deficient glycan extension and endoplasmic reticulum stresses in ALG3-CDG.

ALG3-CDG is a rare congenital disorder of glycosylation (CDG) with a clinical phenotype that includes neurological manifestations, transaminitis, and frequent infections. The ALG3 enzyme catalyzes the first step of endoplasmic reticulum (ER) luminal glycan extension by adding mannose from Dol-P-Man to Dol-PP-Man5GlcNAc2 (Man5) forming Dol-PP-Man6. Such glycan extension is the first and fastest cellular response to ER stress, which is deficient in ALG3-CDG. In this study, we provide evidence that the unfolded protein response (UPR) and ER-associated degradation activities are increased in ALG3-CDG patient-derived cultured skin fibroblasts and there is constitutive activation of UPR mediated by the IRE1-α pathway. In addition, we show that N-linked Man3-4 glycans are increased in cellular glycoproteins and secreted plasma glycoproteins with hepatic or non-hepatic origin. We found that like other CDGs such as ALG1- or PMM2-CDG, in transferrin, the assembling intermediate Man5 in ALG3-CDG, are likely further processed into a distinct glycan, NeuAc1Gal1GlcNAc1Man3GlcNAc2, probably by Golgi mannosidases and glycosyltransferases. We predict it to be a mono-antennary glycan with the same molecular weight as the truncated glycan described in MGAT2-CDG. In summary, this study elucidates multiple previously unrecognized biochemical consequences of the glycan extension deficiency in ALG3-CDG which will have important implications in the pathogenesis of CDG.

Bronchiectasis-associated infections and outcomes in a large, geographically diverse electronic health record cohort in the United States

BackgroundBronchiectasis is a pulmonary disease characterized by irreversible dilation of the bronchi and recurring respiratory infections. Few studies have described the microbiology and prevalence of infections in large patient populations outside of specialized tertiary care centers.MethodsWe used the Cerner HealthFacts Electronic Health Record database to characterize the nature, burden, and frequency of pulmonary infections among persons with bronchiectasis. Chronic infections were defined based on organism-specific guidelines.ResultsWe identified 7,749 patients who met our incident bronchiectasis case definition. In this study population, the organisms with the highest rates of isolate prevalence were Pseudomonas aeruginosa with 937 (12%) individuals, Staphylococcus aureus with 502 (6%), Mycobacterium avium complex (MAC) with 336 (4%), and Aspergillus sp. with 288 (4%). Among persons with at least one isolate of each respective pathogen, 219 (23%) met criteria for chronic P. aeruginosa colonization, 74 (15%) met criteria for S. aureus chronic colonization, 101 (30%) met criteria for MAC chronic infection, and 50 (17%) met criteria for Aspergillus sp. chronic infection. Of 5,795 persons with at least two years of observation, 1,860 (32%) had a bronchiectasis exacerbation and 3,462 (60%) were hospitalized within two years of bronchiectasis diagnoses. Among patients with chronic respiratory infections, the two-year occurrence of exacerbations was 53% and for hospitalizations was 82%.ConclusionsPatients with bronchiectasis experiencing chronic respiratory infections have high rates of hospitalization.

[Oncological relevance of neuro-urological diseases].

Apart from a few exceptions, there is currently little scientific evidence on the oncological relevance of neuro-urological diseases. Most research has been conducted into the association between long-term spinal cord injury with its consequences for the lower urinary tract and the occurrence of bladder cancer. These cancers differ in many ways from bladder cancers in patients without spinal cord injury: patients are 20 years younger on average, tumours are very often already muscle-invasive and poorly differentiated with a high proportion of squamous cell carcinomas, and the prognosis is poor. These characteristics also occur in spinal cord injury patients without permanent catheter drainage of the urinary bladder. Although the pathophysiological association has not been clarified in detail, the presence of a neurogenic bladder appears to be the decisive link between spinal cord injury and the occurrence of bladder cancer. Pathological pressure conditions in the urinary bladder and frequent urinary tract infections or asymptomatic bacteriuria resulting from neurogenic lower urinary tract dysfunction could be the decisive pathophysiological factors. In this respect, urinary bladder cancer in persons with a chronic spinal cord injury represents a model tumour after denervation. The clinically important question of screening requires future interdisciplinary research approaches.

A Review of the Current Status of Anesthetic Management of Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic connective tissue disease of immunological etiology. In the course of the disease, symptoms of the musculoskeletal system predominate, but other systems can also be affected. The disease may require long-term treatment, and patients often require surgery on damaged joints. Complications of the disease and drug interactions may contribute to difficulties in perioperative care; therefore, knowledge is required to provide appropriate care. When anesthetizing a patient with RA, we should pay special attention to preoperative evaluation, taking a medical history, risk of difficult intubation or cardiac incidents, respiratory insufficiency, and frequent pulmonary infections. It is important to be aware of perioperative glucocorticoids supplementation, especially in patients with suspected adrenal insufficiency. Postoperative management, such as pain management, early rehabilitation, and restart of pharmacotherapy play, an important role in the patient's recovery. Special attention should be paid to perioperative management in pregnant women, as the disease is a significant risk factor for complications, and some anesthetic procedures can be noxious to the fetus. Due to the nature of the disease, it can be challenging for the anesthesiologist to provide good and appropriate pain medications, symptom management, and other necessary techniques that are done to anesthetize the patient properly. This work is based on the available literature and the authors' experience. This article aims to review the current status of anesthetic management of patients with rheumatoid arthritis.

Long-Term Treatment With Selective PI3Kδ Inhibitor Leniolisib in Adults With Activated PI3Kδ Syndrome

Activated phosphoinositide 3-kinase delta syndrome (APDS) is an inborn error of immunity that manifests as immune deficiency and dysregulation; symptoms include frequent infections and lymphoproliferation. In our dose-finding and phase 3 placebo-controlled trials, treatment with the selective PI3Kδ inhibitor leniolisib reduced lymphoproliferation and normalized lymphocyte subsets. Here, we present 6 years of follow-up from the 6 adult patients in the original dose-finding trial receiving leniolisib. We used data from the ongoing open-label extension study, which was supplemented at later time points by investigators, including health-related quality of life assessed through a clinician-reported questionnaire. We observed improvements in health-related quality of life: 5/6 patients experienced an increase in physical capabilities and socialization and a decrease in prescribed medications. Immune subsets improved in all patients: mean transitional B-cell levels decreased from 38.17% to 2.47% and the CD4:CD8 T-cell ratio normalized to 1.11. Manifestations seen before and within the first year of leniolisib exposure, such as infections and gastrointestinal conditions, attenuated following year 2 with few new conditions emerging out to year 6. Thrombocytopenia or lymphopenia remained present in half of patients at year 6. Of 83 adverse events through year 5, 90.36% were grade 1; none were grade 4-5 nor deemed leniolisib-related. Collectively, we saw an enhancement in health-related quality of life as well as durable changes in lymphocyte subsets and clinical manifestations, further supporting the use of leniolisib as a long-term therapeutic option for the treatment of APDS. (Funded by Novartis Pharmaceuticals Corporation and Pharming Group NV; ClinicalTrials.gov identifier: NCT02859727.)

Molecular Characterisation and Antibody Response to Bovine Respiratory Syncytial Virus in Vaccinated and Infected Cattle in Turkey

Bovine respiratory syncytial virus (BRSV) is one of the most important respiratory pathogens of cattle. In this study, frequency of infection, analysis of variants, and the immune status of vaccinated and non-vaccinated cattle were studied. Blood (n = 162) and nasal/oropharyngeal (n = 277) swabs were collected from 62 cattle herds in Turkey. Lung samples (n = 37) were also taken from dead animals and abattoirs. Antibodies to BRSV were detected in 76 (46%) out of 162 sera. The antibody levels in the vaccinated and non-vaccinated groups were statistically significant. Among 277 nasal/oropharyngeal swabs and 37 lungs, ten nasal/oropharyngeal and four lung samples were positive for BRSV-RNA. BRSV-G gene sequences of 5 out of 14 RT-PCR positive samples showed that all viruses clustered as Group-III in phylogenetic analysis with 88–100% homology. Similarity with previous Turkish BRSVs was 89–98%, and that with BRSVs detected in the USA and Czechia was 89.47–93.12%. BRSV continues to circulate in Turkish cattle, and vaccination seems beneficial in preventing BRSV. The diversity of the BRSVs found in this study needs be considered in vaccination strategies.

Theoretical considerations and empirical predictions of the pharmaco- and population dynamics of heteroresistance

Antibiotics are considered one of the most important contributions to clinical medicine in the last century. Due to the use and overuse of these drugs, there have been increasing frequencies of infections with resistant pathogens. One form of resistance, heteroresistance, is particularly problematic; pathogens appear sensitive to a drug by common susceptibility tests. However, upon exposure to the antibiotic, resistance rapidly ascends, and treatment fails. To quantitatively explore the processes contributing to the emergence and ascent of resistance during treatment and the waning of resistance following cessation of treatment, we develop two distinct mathematical and computer-simulation models of heteroresistance. In our analysis of the properties of these models, we consider the factors that determine the response to antibiotic-mediated selection. In one model, heteroresistance is progressive, with each resistant state sequentially generating a higher resistance level. In the other model, heteroresistance is non-progressive, with a susceptible population directly generating populations with different resistance levels. The conditions where resistance will ascend in the progressive model are narrower than those of the non-progressive model. The rates of reversion from the resistant to the sensitive states are critically dependent on the transition rates and the fitness cost of resistance. Our results demonstrate that the standard test used to identify heteroresistance is insufficient. The predictions of our models are consistent with empirical results. Our results demand a reevaluation of the definition and criteria employed to identify heteroresistance. We recommend that the definition of heteroresistance should include a consideration of the rate of return to susceptibility.

Letermovir prophylaxis reduced cytomegalovirus reactivation and resistance post umbilical cord blood transplantation.

To explore the impact of letermovir (LET) prophylaxis on cytomegalovirus (CMV) reactivation and resistance in both adult and paediatric umbilical cord blood transplantation (UCBT) patients, we retrospectively compared 43 UCBT patients who received LET as CMV prophylaxis with a historical cohort of 207 UCBT patients without LET usage. LET was administered from Day +1 to Day +100. The 180-day cumulative incidence of CMV reactivation (47.3% vs. 74.4%, p < 0.001) and the proportion of refractory CMV reactivation (15.0% vs. 42.9%, p = 0.016) were significantly lower than those in the control group. However, more frequent late CMV infection (31.0% vs. 4.3%, p = 0.002) and the 180-day cumulative incidence of Epstein-Barr virus (EBV) reactivation (9.3% vs. 3.4%, p = 0.087) were observed in UCBT patients with LET prophylaxis. Meanwhile, older age (>15 years old) and the occurrence of pre-engraftment syndrome were identified as the significant risk factors for CMV reactivation, and in patients at high risk, the incidence of CMV reactivation in the LET group was lower than that in the control group (46.7% vs. 86.5%, p < 0.001), while this decline was less pronounced among patients at low risk (47.8% vs. 62.1%, p = 0.120).

Low-risk Staphylococcus aureus bacteremia patients do not require routine diagnostic imaging: A multicenter retrospective cohort study.

Risk stratification to categorize patients with Staphylococcus aureus bacteremia (SAB) as low- or high-risk for metastatic infection may direct diagnostic evaluation and enable personalized management. We investigated the frequency of metastatic infections in low-risk SAB patients, their clinical relevance, and whether omission of routine imaging is associated with worse outcomes. We performed a retrospective cohort study in seven Dutch hospitals among adult patients with low-risk SAB, defined as hospital-acquired infection without treatment delay, absence of prosthetic material, short duration of bacteremia, and rapid defervescence. The primary outcome was the proportion of patients whose treatment plan changed due to detected metastatic infections, as evaluated by both the actual therapy administered and by linking a retrospectively adjudicated diagnosis to guideline-recommended treatment. Secondary outcomes were 90-day relapse-free survival, and factors associated with performing of diagnostic imaging. Of 377 patients included, 298 (79%) underwent diagnostic imaging. In 15 of these 298 patients (5.0%) imaging findings during patient admission had been interpreted as metastatic infections that should extend duration of treatment. Using the final adjudicated diagnosis, 4 patients (1.3%) had clinically relevant metastatic infection. In a multilevel multivariable logistic regression analysis, 90-days relapse-free survival was similar between patients without imaging and those who underwent imaging (81.0% versus 83.6%; aOR 0.749 (95% CI 0.373-1.504). Our study advocates risk stratification for the management of patients with SAB. Prerequisites are follow-up blood cultures, bedside ID consultation, along with critically reviewing disease evolution. Using this approach, routine imaging could be omitted in low-risk patients.

Abstract CT001: Linvoseltamab, a B-cell maturation antigen-targeted T-cell-engaging bispecific antibody, induces deep and durable responses in patients with relapsed or refractory multiple myeloma including difficult-to-treat subgroups

Abstract Background We report pivotal results from the registrational filing data cut-off (DCO) of the 200 mg dose used in the LINKER-MM1 (NCT03761108) clinical trial, testing the safety and efficacy of linvoseltamab (a B-cell maturation antigen × CD3 antibody [Ab]) as treatment for relapsed/refractory multiple myeloma (RRMM). Methods Eligible patients had RRMM that either progressed on/after ≥3 lines of therapy that included a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 Ab or that was ≥double- (Phase 1) or triple- (Phase 2) class (PI/IMiD/anti-CD38 Ab) refractory. Phase 2 patients received intravenous linvoseltamab once a week through week 14, then once every 2 weeks (Q2W). Phase 2 patients achieving ≥very good partial response (VGPR) who have received treatment for ≥24 weeks transitioned to Q4W dosing. Primary endpoint was objective response rate (ORR) per Independent Review Committee (IRC). Secondary endpoints included duration of response (DOR), progression free survival (PFS), overall survival (OS), and safety. Results At DCO of Sep 8, 2023, median duration of follow-up for the 117 patients enrolled into the 200 mg dosing cohorts (phase 1+2) was 11.1 months (interquartile range 2.9-14.1). Median age was 70 years (26% ≥75), 17% were African American, 18% had International Staging System (ISS) stage III disease, 16% had extramedullary (excluding paramedullary) plasmacytomas (EMPs) ≥2 cm, 39% had high-risk cytogenetics, and 82% were ≥triple-class refractory. Linvoseltamab induced high rates of deep responses with an ORR of 71% including ≥complete response (CR) rate of 46%. Among all patients with ≥CR, 39% were documented minimal residual disease negative. These frequent and deep responses were observed across prespecified high-risk subgroups including patients with ISS stage III (ORR 62%; ≥CR 43%), and EMPs (ORR 53%; ≥CR 26%). Kaplan-Meier (KM) estimated median DOR was not reached (NR); estimated probability of ongoing response at 12 months was 78% (95% confidence interval [CI] 65-86). KM estimated PFS and OS were NR; and probability of PFS and OS at 12 months were 69% (95% CI 58-77) and 75% (65-82), respectively. The most common treatment emergent adverse event (TEAE) was cytokine release syndrome (CRS; any grade [Gr] 46%, Gr2 10%, Gr3 1%, Gr≥4 0%), which occurred mostly during step-up dosing of linvoseltamab with a median time to onset of 11 hours. Other common TEAEs were neutropenia (any Gr 41%, Gr 3-4 40%), anemia (39%, 31%), cough (36%, 0%), and diarrhea (35%, 2%). Infections occurred in 73% (Gr 3-4 34%) of patients. The frequency and severity of infections decreased after 6 months coincident with Q4W dosing. Conclusions Linvoseltamab induced high rates of deep and durable responses in patients with RRMM including those in high-risk subgroups. Linvoseltamab is associated with a generally predictable timing of CRS, and the Q4W response adapted schedule in patients with ≥VGPR may provide a substantial benefit for patient convenience and is associated with a reduced infection rate. Citation Format: Sundar Jagannath, Joshua Richter, Madhav V. Dhodapkar, James E. Hoffman, Hans C. Lee, Attaya Suvannasankha, Mansi R. Shah, Suzanne Lentzsch, Jeffrey A. Zonder, Rachid Baz, Joseph J. Maly, Swathi Namburi, Ka Lung Wu, Matthew Pianko, Rebecca Silbermann, Chang-Ki Min, Marie-Christiane Vekemans, Markus Munder, Ja Min Byun, Joaquín Martínez Lopez, Michelle DeVeaux, Dhruti Chokshi, Anita Boyapati, Anasuya Hazra, Karen Rodriguez Lorenc, Glenn S. Kroog, Yariv Houvras, Naresh Bumma. Linvoseltamab, a B-cell maturation antigen-targeted T-cell-engaging bispecific antibody, induces deep and durable responses in patients with relapsed or refractory multiple myeloma including difficult-to-treat subgroups [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT001.

Nijmegen syndrome in childhood: a clinical case

Nijmegen syndrome is a rare monogenic pathology with an autosomal recessive type of inheritance. The disease is manifested by congenital developmental anomalies and microcephaly, primary immunodeficiency, frequent recurrent viral and bacterial infections, retardation in physical and neuropsychic development. In the medical literature, 150 cases of the syndrome are described; pathology occurs more often among the Slavic population. Nijmegen syndrome belongs to a group of diseases with chromosomal instability. The pathogenetic feature of the syndrome is congenital immunodeficiency of the humoral (B-lymphocytes) and cellular (T-lymphocytes) components. According to statistics, 40 % of children with Nijmegen syndrome are diagnosed with malignant neoplasms. lymphoid tissue is more often affected (non-Hodgkin’s B and T-cell lymphomas, acute lymphoblastic leukemia), and the development of solid neoplasia is also possible. To diagnose Nijmegen syndrome, in addition to assessing the patient clinical status, it is necessary to conduct an extended immunological examination with the determination of immunoglobulins A, M, G and molecular genetic studies.The article presents a clinical case of diagnosis and treatment of Nijmegen syndrome in childhood.

A novel termination site in a case of Stüve–Wiedemann syndrome: case report and review of literature

Stüve–Wiedemann syndrome (SWS) is a rare autosomal recessive disorder that is characterized by bowing of long bones, dysautonomia, temperature dysregulation, swallowing and feeding difficulties, and frequent respiratory infections. Respiratory distress and hyperthermic events are the leading causes of early neonatal death, and most patients are not expected to survive past infancy. Here, we report on the survival of a 5-year-old male with SWS, discussing his case presentation, providing a brief clinical course, and discussing the outcome. This case adds to the literature surrounding rare instances of childhood survivors of SWS and raises awareness for this syndrome to facilitate an earlier recognition, intervention, and genetic counseling for the families, thereby improving understanding of this disease and the health outcomes for the children affected by this condition.

Do early-life allergic sensitization and respiratory infection interact to increase asthma risk?

Objective The ‘two-hit’ hypothesis theorizes that early life allergic sensitization and respiratory infection interact to increase asthma risk. Methods We sought to determine in a high allergy risk birth cohort whether interactions between early life allergic sensitization and respiratory infection were associated with increased risk for asthma at ages 6–7 years and 18 years. Allergic sensitization was assessed at 6, 12, and 24 months by skin prick testing to 3 food and 3 aeroallergens. Respiratory infection was defined as reported “cough, rattle, or wheeze” and assessed 4-weekly for 15 months, at 18 months, and age 2 years. Regression analysis was undertaken with parent-reported asthma at age 6–7 years and doctor diagnosed asthma at 18 years as distinct outcomes. Interactions between allergic sensitization and respiratory infection were explored with adjustment made for potential confounders. Results Odds of asthma were higher in sensitized compared to nonsensitized children at age 6–7 years (OR = 14.46; 95% CI 3.99–52.4), There was no evidence for interactions between allergic sensitization and early life respiratory infection, with a greater frequency of respiratory infection up to 2 years of age associated with increased odds for asthma at age 6–7 years in both sensitized (OR = 1.13; 95% CI 1.02–1.25, n = 199) and nonsensitized children (OR = 1.31; 1.11–1.53, n = 211) (p interaction = 0.089). At age 18 years, these associations were weaker. Conclusions Our findings do not support ‘two-hit’ interactions between early life allergic sensitization and respiratory infection on asthma risk. Both early life respiratory infections and allergic sensitization were risk factors and children with either should be monitored closely for development of asthma.

Prevalence of Antibiotic Use in Hospitalized COVID-19 Patients: An Observational Study in Secondary Healthcare Hospitals in Kosovo

INTRODUCTION: Globally, the high use of antibiotics among hospitalized patients diagnosed with COVID-19 has been reported despite evidence that bacterial coinfections are uncommon. This issue raised our concerns, as there was a report on high frequency of antibiotic resistant bacterial infections in COVID-19 patients admitted to the intensive care unit. Thus, we conducted a study to determine the prevalence of antibiotic use for hospitalized acute COVID-19 infection in secondary healthcare hospitals in Kosovo. MATERIALS AND METHODS: A cross sectional study was conducted among patients with acute COVID-19 admitted to secondary healthcare hospitals in Kosovo. A modified Infectious Diseases International Research Initiative (ID-IRI) questionnaire was used to collect information in 460 COVID-19 PCR positive patients. RESULTS: All studied patients (100%) were treated with antibiotics. An empirical antibiotics were used to cover Methicillin-resistant Staphylococcus aureus (MRSA) infections in 136 cases (29.6%), methicillin-susceptible Staphylococcus aureus (MSSA) infections in 86 cases (18.7%), atypical pathogen in 174 cases (37.8%), and Pseudomonas infections in 48 cases (10.4%). The most frequently used antibiotics were ceftriaxone/cefotaxime plus macrolide (149 cases; 31%), ceftriaxone/cefotaxime plus quinolone (85 cases; 17.7%), and co-amoxiclav plus fluoroquinolone (78 cases; 16.3%). Imipenem was most frequently used in the ICU (64 cases; 13.3%). CONCLUSION: Despite the antibiotic guidelines clearly stated that antibiotics should only be used in confirmed case of secondary bacterial infections including the COVID-19 patients, our study revealed that the overused of antibiotics remained unchanged. As the misused and overused of antibacterial has been shown to accelerate the emergence and spread of antibacterial resistant, the inappropriate practice should be changed.

Hospitalization and Mortality due to Infection among United States Children and Adolescents with Systemic Lupus Erythematosus.

We aimed to determine the frequency and types of infections in hospitalized children with childhood-onset systemic lupus erythematosus (cSLE), and to identify risk factors for intensive care unit (ICU) admission and mortality. We conducted a retrospective study of youth 2-21 years of age with ICD codes for SLE during admission to a hospital participating in the Pediatric Health Information System, a database of United States children's hospitals, from 2009-2021. Generalized linear mixed effect models were used to identify risk factors for ICU admission and mortality among children hospitalized with infection. We identified 8,588 children with cSLE and ≥ 1 hospitalization. Among this cohort, there were 26,269 hospitalizations, of which 13% had codes for infections, a proportion which increased over time (p = 0.036). Bacterial pneumonia was the most common hospitalized infection. In-hospital mortality occurred in 0.4% (n=103) of cSLE hospitalizations for any indication and 2% of hospitalizations for infection (n=60). The highest mortality rates occurred with pneumocystis jirovecii pneumonia (21%) and other fungal infections (21%). Lupus nephritis and end-stage renal disease (ESRD) were associated with increased odds of ICU admission (OR [95% CI] 1.47 [1.2- 1.8]) and 2.4 [1.7-3.4]) among children admitted for serious infection. ESRD was associated with higher mortality, OR 2.34 [1.1-4.9]. Hospitalizations with codes for for infection comprised a small proportion of cSLE admissions but accounted for the majority of mortality. The proportion of hospitalizations for infection increased over time. Lupus nephritis and ESRD were risk factors for poor outcomes.