Progressive bronchiectasis and CMC in a patient with STAT1 GOF — a rare case of primary immunodeficiency

Bronchiestasis is a common complication developing in patients with primary immunodeficiency disorders. AD GOF STAT1 defi-ciency is characterized by CMC, repeated infections, and autoimmunity. It is the most frequently diagnosed entity in a group of PIDs with CMC. Here, we present the first Polish case of a female patient with early-onset bronchiestasis accompanied by CMC and a severe course of infections who was genetically diagnosed with AD GOF1 STAT1 mutation at the age of 15

The "Wholesome Contact" non-pharmacological, volunteer-delivered multidisciplinary programme to prevent hospital delirium in elderly patients : study protocol for a randomised controlled trial

Background: In hospital settings, delirium affects as many as 50% of older patients, aggravating their symptoms and worsening their condition, and therefore increasing the risk of in-hospital complications and death. The aim of this study is to assess the efficacy of structured, non-pharmacological care, delivered to older hospitalised patients by trained volunteers (students of medical fields), on the reduction of incidence of adverse health-related outcomes. Methods/design: This trial will be a randomised, investigator-blind, controlled trial conducted in an internal medicine and geriatric ward in Poland. We aim to include 416 patients who are 70 years of age and have been hospitalised for medical reasons. Eligible patients will be randomised 1:1 to receive structured, non-pharmacological care delivered by students of medicine, psychology and nursing, together with standard medical treatment or standard medical care alone. The protocol of interventions has been designed to cover nine main risk factors for delirium, with the scope of multidisciplinary interventions being individualised and tailored. The protocol will be aimed at immobilisation, vision and hearing impairment, cognitive impairment and disorientation, stress and anxiety, sleep–wake cycle disturbances, dehydration and malnutrition, and pain. A structured evaluation of patients’ cognition, mood, anxiety and functional performance is planned to be carried out twice, on the day of group allocation and at discharge; structured screening assessment for delirium will be conducted daily using the Confusion Assessment Method. The primary outcome will be the incidence of delirium in hospital; secondary outcomes will be in-hospital changes in cognition, mood and anxiety, and functional status, occurrence of falls and death. Discussion: Delirium prevention programmes are being introduced worldwide. A particular novelty of our project, however, is that invitations for voluntary work with older patients at risk for delirium will be addressed to medical students. With the use of the service learning method, the students will shape their attitudes, increase their knowledge and understanding of hospital care, and master competencies to work within interdisciplinary teams, which establishes the originality and practicality of the project

SARS-CoV-2 antibody response after mRNA vaccination in healthcare workers with and without previous COVID-19, a follow-up study from a university hospital in Poland during 6 months 2021

IntroductionHealthcare workers (HCWs) from the beginning of the pandemic have been at risk of exposure to SARS-CoV-2, so they were vaccinated as first.ObjectivesThe purpose of the study was to determine the level of antibodies against SARS-CoV-2 in HCWs before and after vaccination with mRNA preparations according to previous COVID- 19.Patients and methodsThe HCWs from the University Hospital in Krakow completed two surveys: the baseline survey before receiving the first dose of vaccine (in January 2021) and the follow-up survey in June 2021. In parallel, two blood samples were collected from each participant at baseline and at follow-up. Total anti-SARS-CoV-2 antibody levels were measured using the ECLIA technique.ResultsAt baseline, 41.1% of HCWs had positive antibody test results, and at follow-up, the vaccinated HCWs had almost 100 times higher antibody levels than the unvaccinated HCWs. Participants under 30 years of age had significantly higher antibody levels in June than older HCWs. Among participants with positive antibody test results in January, HCWs who had experienced asymptomatic COVID-19 had more than five times higher antibody levels in June than HCWs self-reported severe COVID-19. In total, 86.9% of HCWs received Comirnaty or Spikevax. The incidence rate of COVID-19 in the unvaccinated vs. vaccinated group was 13 times higher, 20.5% and 1.9% respectively.ConclusionsThese results confirm the effectiveness of vaccination in the prevention of COVID-19 in HCWs. It is worth getting vaccinated regardless of previous infection. Furthermore, vaccination among HCWs under 30 years of age induced more effective antibody production compared to older individuals

National experience with adenosine deaminase deficiency related SCID in Polish children

IntroductionDeficiency of adenosine deaminase (ADA) manifests as severe combined immunodeficiency (SCID), caused by accumulation of toxic purine degradation by-products. Untreated patients develop immune and non-immune symptoms with fatal clinical course. According to ESID and EBMT recommendations enzyme replacement therapy (ERT) should be implemented as soon as possible to stabilize the patient’s general condition, normalize transaminases, treat pulmonary proteinosis, bone dysplasia, and protect from neurological damage. Hematopoietic stem cell transplantation (HSCT) from a matched related donor (MRD) is a treatment of choice. In absence of such donor, gene therapy (GT) should be considered. HSCT from a matched unrelated donor (MUD) and haploidentical hematopoietic stem cell transplantation (hHSCT) are associated with worse prognosis.Material and methodsWe retrospectively evaluated the clinical course and results of biochemical, immunological and genetic tests of 7 patients diagnosed in Poland with ADA deficiency since 2010 to 2022.ResultsAll patients demonstrated lymphopenia affecting of T, B and NK cells. Diagnosis was made on the basis of ADA activity in red blood cells and/or genetic testing. Patients manifested with various non-immunological symptoms including: lung proteinosis, skeletal dysplasia, liver dysfunction, atypical hemolytic-uremic syndrome, and psychomotor development disorders. Five patients underwent successful HSCT: 3 patients from matched unrelated donor, 2 from matched sibling donor, and 1 haploidentical from a parental donor. In 4 patients HSCT was preceded by enzyme therapy (lasting from 2 to 5 months). One patient with multiple organ failure died shortly after admission, before the diagnosis was confirmed. None of the patients had undergone gene therapy.ConclusionsIt is important to diagnose ADA SCID as early as possible, before irreversible multi-organ failure occurs. In Poland HSCT are performed according to international immunological societies recommendations, while ERT and GT are less accessible. Implementation of Newborn Screening (NBS) for SCID in Poland could enable recognition of SCID, including ADA-SCID

EuroFlow Standardized Approach to Diagnostic Immunopheneotyping of Severe PID in Newborns and Young Children

The EuroFlow PID consortium developed a set of flow cytometry tests for evaluation of patients with suspicion of primary immunodeficiency (PID). In this technical report we evaluate the performance of the SCID-RTE tube that explores the presence of recent thymic emigrants (RTE) together with T-cell activation status and maturation stages and discuss its applicability in the context of the broader EuroFlow PID flow cytometry testing algorithm for diagnostic orientation of PID of the lymphoid system. We have analyzed peripheral blood cells of 26 patients diagnosed between birth and 2 years of age with a genetically defined primary immunodeficiency disorder: 1

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood : An individual participant data meta-analysis

Background Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. Methods and findings We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestylerelated characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p <0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. Conclusions In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.Peer reviewe

Gestational weight gain charts for different body mass index groups for women in Europe, North America, and Oceania

BackgroundGestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies.MethodsWe used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape.ResultsWe observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40weeks was 14.2kg (11.4-17.4) for underweight women, 14.5kg (11.5-17.7) for normal weight women, 13.9kg (10.1-17.9) for overweight women, and 11.2kg (7.0-15.7), 8.7kg (4.3-13.4) and 6.3kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications.ConclusionsGestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.Peer reviewe