East Tallinn Central Hospital

This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA2LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Germline genetic testing (GT) of cancer-associated genes enables the identification of hereditary risk in breast (BC) and ovarian cancer (OC) patients, supporting early diagnosis and personalized treatment strategies. In this study, we analyzed data from 3,537 patients who underwent routine clinical GT in Estonia between 2007–2023, including 2,856 BC and 759 cases of OC. A total of 78 individuals in the study were diagnosed with both BC and OC. The mean age at diagnosis and GT was 50.4 ± 12.0 and 54.0 ± 12.5 years for BC, and 56.1 ± 14.1 and 59.4 ± 13.3 years for OC, respectively. Non-genetic medical specialists ordered most GT (66.1%). GT increased nine-fold over the course of the study period. Altogether, 687 pathogenic/likely pathogenic variants (PV) were identified in 668 individuals (17.4% in BC, 26.0% in OC), with an overall combined PV detection rate of 18.9%. The most frequently mutated genes were BRCA1 (6.9% BC; 16.3% OC), BRCA2 (3.8%; 4.5%), and CHEK2 (3.5%; 1.7%). Two BRCA1 PV, c.5266dup and c.4035del, accounted for 29.1% of all PV detected. In addition to BRCA1/2, we identified 19 non-BRCA cancer susceptibility genes in 243 individuals and 25 novel PV, which demonstrates the importance of multi-gene NGS-based GT in Estonia for identifying hereditary cancer risk.

BackgroundHereditary angioedema (HAE) is a rare, potentially life-threatening disorder characterised by recurrent episodes of localised oedema caused by bradykinin overproduction. Accurate epidemiological data are essential for optimising diagnosis and treatment, particularly in underrepresented regions such as the Baltic states. This study aimed to examine the prevalence, clinical characteristics, genetic variants, and treatment accessibility for patients with HAE in the Baltic states of Estonia, Latvia, and Lithuania.MethodsThis retrospective study included HAE patients diagnosed according to the WAO/EAACI 2021 criteria between 2004 and 2024. Demographic, clinical, and genetic data were collected and evaluated. Descriptive statistical analysis was performed using Jamovi (version 2.3).ResultsA total of 78 patients were identified in Estonia (n=30), Latvia (n=12) and Lithuania (n=36) from 2004 till 2024. In Lithuania, 7 patients had died and 3 were lost to follow-up, resulting in 26 patients remaining under active observation. While the total number of HAE cases identified across the three countries was reported, detailed clinical data and analyses were limited to the 68 patients who were alive and actively followed at the time of data collection. Estonia exhibited the highest point prevalence (2.19 per 100, 000), while Latvia had the lowest (0.65). The median diagnostic delay was longest in Latvia (24 years) and shortest in Estonia (9.5 years). SERPING1 gene pathogenic variants predominated. Estonia had the broadest availability of treatments, whereas Latvia had restricted access to modern therapies.ConclusionConsiderable variation exists in HAE prevalence, diagnosis, and treatment across the Baltic states. Estonia exemplifies best practices, while Latvia remains underserved. Regional collaboration and standardised care protocols are urgently needed.

Importance:Controversies persist about management of the ductus arteriosus by nonsteroidal anti-inflammatory drugs in extremely preterm infants. Acetaminophen (paracetamol) appears to be a promising alternative with possibly fewer adverse effects. Objective:To evaluate whether prophylactic intravenous acetaminophen started within 12 hours of birth increases survival without neonatal severe morbidities at 36 weeks' postmenstrual age. Design, Setting, and Participants:A double-blind, randomized, placebo-controlled clinical trial was conducted among preterm infants born between 23 weeks 0 days and 28 weeks 6 days of gestation in 43 neonatal intensive care units of 14 European countries between October 2020 (October 2021 for infants born at 23-26 weeks' gestation, after the phase 2 study identified the optimal dose of acetaminophen) and April 2024. Data analysis was conducted from January to June 2025. Intervention:In the acetaminophen group, patients born at 27 to 28 weeks' gestation received a 20-mg/kg loading dose of acetaminophen followed by 7.5 mg/kg every 6 hours for 5 days, and patients born at 23 to 26 weeks' gestation received a 25-mg/kg loading dose of acetaminophen followed by 10 mg/kg every 6 hours for 5 days. In the placebo group, isotonic sodium chloride was administered. Main Outcomes and Measures:The primary outcome was survival without neonatal morbidity evaluated at 36 weeks' postmenstrual age. The secondary exploratory outcome was ductus arteriosus closure, assessed by echocardiography on day 7. Results:A total of 778 patients (median [IQR] gestational age, 26 [25-27] weeks; 375 [48.2%] female) were included in the study, with 391 in the acetaminophen group and 387 in the placebo group. Survival without severe morbidities at 36 weeks' postmenstrual age occurred in 259 infants (66.2%) in the acetaminophen group and 246 (63.6%) in the placebo group (absolute risk difference [ARD], 2.7 [95% CI, -4.0 to 9.3] percentage points; relative risk [RR], 1.04 [95% CI, 0.94 to 1.16]). The ductus arteriosus was considered closed on day 7 in 264 of 371 infants (71.2%) assigned to acetaminophen and 191 of 366 infants (52.2%) assigned to placebo (ARD, 19.0 [95% CI, 12.0 to 25.7] percentage points; RR, 1.36 [95% CI, 1.21 to 1.53]). In the safety analysis, adverse events were not different except for a higher cholestasis rate in the acetaminophen group (25 of 392 infants [6.4%]) vs the placebo group (10 of 386 infants [2.6%]) (ARD, 3.8 [95% CI, 0.9 to 6.9]) percentage points. Conclusions and Relevance:This study found that prophylactic acetaminophen treatment for patent ductus arteriosus did not increase survival without neonatal morbidities. Trial Registration:ClinicalTrials.gov Identifier: NCT04459117.

Peripheral arterial disease (PAD) affects millions of people worldwide and often goes undetected until advanced stages. Electrical bioimpedance spectroscopy (EIS) offers a potential non-invasive, low-cost, and continuous monitoring modality for peripheral perfusion. This paper presents the first feasibility results of a custom, portable EIS system measuring wrist and foot tissue impedance during controlled, transient cuff-occlusion ischemia (brachial cuff on the arm, thigh cuff on the leg) in a single healthy volunteer. The study evaluates equipment performance and protocol feasibility rather than diagnostic accuracy or clinical validation; the results are descriptive and do not support statistical inference. Spectra were acquired across 12 logarithmically spaced frequencies from 1 kHz to 560 kHz at a rate of approximately one spectrum per 6 s. During arm ischemia (≈2.9 min occlusion) the impedance magnitude at 100 kHz increased by 1.6%, consistent with a reduction in blood volume in the measurement zone. During foot ischemia (≈5.1 min occlusion) the impedance decreased by 0.6% at 100 kHz, suggesting venous pooling dominates the response at that site. Phase changes up to 1° were observed. The reperfusion phase additionally yielded site-specific exponential recovery time constants ( vascular-reactivity τ ≈ 7 to 11 min) and reactive overshoots, providing candidate markers for future study in PAD. These results demonstrate that the custom EIS system is sensitive to ischemia-induced tissue changes and reperfusion dynamics, and motivate a larger clinical study in PAD patients.