Fatal Reactions Research Articles

Nonsteroidal anti-inflammatory drugs-associated vanishing bile duct syndrome: a real-world retrospective and disproportionality analysis

ABSTRACT Introduction Vanishing bile duct syndrome (VBDS) is a potentially fatal adverse reaction triggered by certain medications. The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and VBDS is based on case reports. We explored the reporting prevalence and evaluated the clinical features of NSAID-related VBDS. Research design and methods Adverse event reports of VBDS associated with NSAIDs from 2004 to 2023 in the FAERS database were retrieved, and disproportionality analyses were conducted to detect risk signals. Case reports from 2000 to 2023 on NSAID-induced VBDS were retrieved for retrospective analysis. Results We obtained 87 VBDS reports from the FAERS database. Ibuprofen had the greatest proportion of VBDS (63.2%), while loxoprofen had the highest positive signal value. Sixteen case reports showed evidence of VBDS, with 37.5% of children. The median age was 29 years; typical initial symptoms included rash (60.0%), jaundice (53.3%), fatigue/asthenia (33.3%), and SJS/TEN (53.3%). The median onset time of VBDS was 4 weeks. All cases had abnormal liver function tests, with the median level of TBIL being 20.0 mg/dl. The overall prognosis is poor, with 50% of patients achieving clinical remission. Conclusion Four NSAID agents had significant reporting associations with VBDS. Prescribers should be more aware of this risk and identify signs/symptoms earlier.

Spatial proteomics identifies JAKi as treatment for a lethal skin disease.

Toxic epidermal necrolysis (TEN) is a fatal drug-induced skin reaction triggered by common medications and is an emerging public health issue1-3. Patients with TEN undergo severe and sudden epidermal detachment caused by keratinocyte cell death. Although molecular mechanisms that drive keratinocyte cell death have been proposed, the main drivers remain unknown, and there is no effective therapy for TEN4-6. Here, to systematically map molecular changes that are associated with TEN and identify potential druggable targets, we utilized deep visual proteomics, which provides single-cell-based, cell-type-resolution proteomics7,8. We analysed formalin-fixed, paraffin-embedded archived skin tissue biopsies of three types of cutaneous drug reactions with varying severity and quantified more than 5,000 proteins in keratinocytes and skin-infiltrating immune cells. This revealed a marked enrichment of type I and type II interferon signatures in the immune cell and keratinocyte compartment of patients with TEN, as well as phosphorylated STAT1 activation. Targeted inhibition with the pan-JAK inhibitor tofacitinib in vitro reduced keratinocyte-directed cytotoxicity. In vivo oral administration of tofacitinib, baricitinib or the JAK1-specific inhibitors abrocitinib or upadacitinib ameliorated clinical and histological disease severity in two distinct mouse models of TEN. Crucially, treatment with JAK inhibitors (JAKi) was safe and associated with rapid cutaneous re-epithelialization and recovery in seven patients with TEN. This study uncovers the JAK/STAT and interferon signalling pathways as key pathogenic drivers of TEN and demonstrates the potential of targeted JAKi as a curative therapy.

Antipyretic effect of oral dipyrone (Metamizole) compared to oral ibuprofen in febrile children: a systematic review and meta-analysis

BackgroundDipyrone (Metamizole) is a potent pain reliever and fever reducer with muscle relaxant properties, most commonly used as an analgesic and antipyretic agent. Despite the fact that it has been banned in many high-income countries following confirmed studies of fatal agranulocytosis and adverse drug reactions, it is still widely used in various countries of the world. However, the antipyretic therapeutic indications of dipyrone in febrile children are currently unknown, and there is little information on the advantages and disadvantages of using dipyrone in febrile children. In febrile children, we expected that dipyrone’s antipyretic effectiveness wouldn’t be any more effective than ibuprofen. Therefore, the purpose of this research is to evaluate the effectiveness of oral dipyrone and oral ibuprofen as antipyretics in febrile children.MethodsSeveral databases, including PubMed, Scopus, Web of Science, and Cochrane Library, were searched thoroughly using a pre-established search strategy for potential research. The studies included in this analysis comprised randomized controlled trials that compared the antipyretic effects of oral ibuprofen and oral dipyrone in febrile children. Data analysis was carried out using RevMan 5.4 software.ResultsThree studies were selected among the 27 publications we discovered to be applicable, and they underwent qualitative and quantitative analysis. The pooled analysis revealed no discernible difference between oral dipyrone and oral ibuprofen in terms of their antipyretic effects (Mean difference (MD) = 0.06; 95% confidence interval (CI): -0.08, 0.20).ConclusionBoth oral dipyrone and ibuprofen are effective in reducing high-temperature levels in febrile children without any significant difference.

Drug-induced hypersensitivity syndrome due to phenytoin: Case report and review of the literature.

Drug hypersensitivity syndrome (DIHS) is a rare but potentially fatal adverse drug reaction characterized by fever, rash, and visceral organ damage, particularly affecting the liver. Early recognition and appropriate management are crucial to prevent serious complications. However, there is limited information on the clinical presentation and management of DIHS, especially in the context of antiepileptic drugs. This case report aims to highlight the importance of recognizing subtle clinical signs and symptoms of DIHS, which can be easily overlooked, particularly in the context of antiepileptic drug use. We report a case of a 15-year-old male patient who developed DIHS after being prescribed phenytoin sodium for epilepsy. The patient presented with symptoms of fever, sore throat, rash, jaundice, and liver dysfunction. Initially, the patient did not receive glucocorticoids and experienced additional reactions to cefoxitin and phosphatidylcholine, likely due to cross-reactivity. The diagnosis of DIHS was made based on the patient's clinical presentation, including fever, extensive rash, organ involvement, and hematological abnormalities. The temporal association with the use of phenytoin sodium, along with the exclusion of other causes of fever and rash, supported the diagnosis. Upon initiation of glucocorticoid therapy with dexamethasone, the patient's symptoms significantly improved. The rash and pruritus decreased, and laboratory values showed improvement, with a decrease in liver enzymes and normalization of white blood cell counts. The patient's fever resolved within 48 hours of starting corticosteroids, and there was no evidence of ongoing inflammation as indicated by a decrease in C-reactive protein levels. Furthermore, the patient's 30-month follow-up revealed no recurrence of rash, liver dysfunction, or organic damage, indicating the long-term effectiveness of the treatment administered. This case highlights the importance of recognizing the subtle clinical signs and symptoms of DIHS, especially in the context of antiepileptic drug use. It underscores the potential benefits of early initiation of glucocorticoid therapy in managing DIHS. The case also serves as a reminder of the potential for drug cross-reactivity in DIHS and the need for cautious drug selection during the acute phase of the syndrome.

Dog Blood Type DEA 1 in Two Municipalities of Luanda Province of Angola (Sub-Saharan Africa).

In dogs, the risk of an acute hemolytic transfusion reaction at the first transfusion is negligible; however, mismatched transfusions may produce alloimmunization. To avoid fatal acute hemolytic reactions in subsequent blood transfusions, it is important to recognize blood groups and to blood type both the donor and the recipient. Prevalence of dog blood groups varies geographically and between breeds. Our aim was to determine DEA 1 prevalence in a canine population in Luanda (Angola) and to assess alloimmunization risk after a mismatched blood transfusion. Blood samples were typed using an immunochromatographic strip technique. Of the 112 dogs tested (59 males; 53 females), 52.68% were DEA 1 positive and 47.32% DEA 1 negative. Females tended to be DEA 1 positive, and males DEA 1 negative (p = 0.0085). In a first-time mismatched blood transfusion, the calculated probability of a dog becoming sensitized was 24.9% and the probability of an acute hemolytic reaction following a second incompatible blood transfusion was 6.21%. DEA 1 prevalence obtained was similar to that reported worldwide, but differs from other African countries. The risk of alloimmunization and acute hemolytic transfusion reactions in mismatched blood transfusions is higher than that in other African regions. Blood typing is recommended prior to transfusion.

Síndrome Dress por uso de Trimetropin Sulfametoxazol

The term DRESS was introduced in 1996 to describe a drug reaction with eosinophilia, skin eruption and systemic symptoms. Potentially fatal drug reactions include three distinct entities: DRESS syndrome, acute generalized exanthem and Stevens-Johnson syndrome/toxic epidermal necrolysis. We report a case of DRESS syndrome in a female patient who attended Hospital de San José in Bogotá, for presenting a cutaneous reaction induced by trimethroprim/sulfamethoxazole. The physiopathology, diagnosis, clinical features and treatment, are outlined herein.

MET exon 14 skipping mutations in non-small-cell lung cancer: real-world data from the Italian biomarker ATLAS database

Mesenchymal-epithelial transition (MET) exon 14 (METex14) skipping mutation is a rare alteration in non-small-cell lung cancer (NSCLC), occurring in about 3%-4% of cases. Here we report disease and patient characteristics, and efficacy and tolerability of MET inhibitors among advanced METex14 NSCLC patients from the Italian real-world registry ATLAS. Clinical-pathological and molecular data, and treatment efficacy/tolerability outcomes were retrospectively collected from the ATLAS registry. From July 2020 to July 2023 a total of 146 METex14 advanced NSCLC patients were included across 27 Italian centers. Median age was 74 years, and most patients were male (52%), with an Eastern Cooperative Oncology Group performance status < 2 (72%) and adenocarcinoma subtype (83%). One hundred and twenty-five out of 146 (86%) patients received at least one line of systemic anticancer therapy. Fifty-six (38%) were treated with capmatinib and 34 (23%) with tepotinib. 29% and 52% of them received targeted treatment in the first and second line, respectively. In the cohort of patients treated with MET inhibitors, the response rate (RR) was 37% (33% in previously treated patients and 46% in treatment-naïve) with a disease control rate of 62%. With a median follow-up of 10.8 months, progression-free survival was 6.6 months [95% confidence interval (CI) 4.3-8.3 months] and overall survival was 10.7 months (95% CI 7.2-19.3 months). In patients with measurable brain metastases (17 cases), the intracranial RR was 41%. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 12% of patients with grade 3 peripheral edema in 7% of cases. A fatal adverse reaction occurred in one patient due to pneumonitis. TRAEs-related dose reduction and discontinuation were reported in 6% and 8% of cases, respectively. Capmatinib and tepotinib represent an effective treatment option in NSCLC patients with METex14. Real-world efficacy outcomes are worse than those reported in prospective clinical trials. Their activity is more pronounced in the treatment-naïve population, suggesting that this is the right setting in the management of patients with METex14.

Anaphylaxis after SonoVue: A Case Report and a Literature Review.

SonoVue (Bracco, Milan, Italy) is a drug used in ultrasonography for the purpose of increasing the echogenicity of blood or fluids by improving the signal-to-noise ratio. Background/Objectives/Methods: We described a case of anaphylaxis due to SonoVue and performed a literature review. Results and Conclusions: We reported a case of anaphylaxis secondary to the administration of SonoVue and described all the 13 literature cases. Given its widespread use and the potentially dangerous nature of the reactions it can cause, it is advisable to know how to promptly recognize fatal reactions.

Green-synthesized Metal Nanoparticles for Cancer Diagnosis and Treatment: A Critical Review

: The utilization of chemotherapy remains an established therapeutic strategy in the ongoing fight against cancer. Nevertheless, it has been impeded by the occurrence of several fatal adverse reactions caused by non-specific toxicity often associated with chemotherapy. Nanotechnology is an emerging field of research that is experiencing rapid growth and is widely recognized as a highly promising approach for advanced cancer therapy. Biosynthesized green nanomaterials are emerging as promising tools for cancer treatment and diagnosis. Metal nanoparticles have been developed for use in several applications, including magnetically sensitive medication delivery, photothermal treatment, and photoimaging. Nanomaterials containing metals, such as iron, cobalt, and silver, which are generated from various bio-sources, have been described. The boundless capabilities of nanoparticles have already had a profound impact on human existence. Nevertheless, the potential adverse effects of nanoparticles on human health have consistently instilled apprehension. A thorough investigation of the toxicity and intricate nature of nanomaterials has facilitated the emergence of nanotoxicology, a field that examines the fundamental origins of these problems. The introduction of green chemistry principles has aimed to provide safer techniques for the production and management of nanomaterials, resulting in the emergence of green nanotechnology. This review article highlights the potential uses of green nanotechnology for the detection and management of tumors, including the challenges they face in reaching clinical trials.

Bee Sting Injuries in Thailand's High Apicultural Area: Outcome, Risk and Treatment Patterns.

This study aims to assess the clinical outcomes and risk factors associated with severe systemic reactions following bee stings, focusing on patients treated at Pa-Sang Community Hospital, located in Lamphun Province, Thailand, which is recognized as one of the country's largest apicultural areas. A retrospective review was conducted, utilizing electronic medical records with ICD-10 coding, of patients treated for bee sting injuries at the Emergency Department of Pa-Sang Hospital from January 2015 to December 2019. This analysis included a total of 591 bee sting events involving 533 patients. The average incidence of bee sting injuries was 31.3 per 10,000 Emergency Department visits, with 55% being male. A significant majority (86%) of events occurred outside the patients' home area. Notably, the head or extremities (49%) were the most common anatomical sites stung. Systemic reactions were observed in 44% of cases, with 96 visits (16%) diagnosed as anaphylaxis. Epinephrine injection was administered in 77% of these cases, and fortunately, no fatal anaphylactic reactions were recorded. Protective factors for anaphylaxis and severe systemic reactions after bee stings included age less than 15 years old and stings on extremities. Conversely, having more than ten bee stings and seeking Emergency Department treatment within 60 minutes of being stung were identified as significant risk factors. Bee sting injuries were a common presentation at the hospital situated in the high apicultural area, and severe systemic reactions were observed. This study highlights the need for comprehensive interventions to mitigate the increased risk of bee-related accidents in communities with thriving apicultural industries.

Toxic Epidermal Necrolysis by Lamotrigine - A Case Report of Fatality

Toxic epidermal necrolysis (TEN) is an immune mediated fatal adverse muco-cutaneous drug reaction characterized by extensive exfoliation of the epidermis and mucous membrane. It may result in sepsis and death. In most cases, TEN is caused by certain drugs &amp; vaccines. TEN involves more than 30% of body surface area. Steven Johnson Syndrome also shows the same disease process and same spectrum of drug-induced epidermolysis. A 37-year-old patient who was on Lamotrigine, Escitalopram &amp; Clonazepam for multiple somatoform disorder developed generalized vesicular rash with fever after 2 weeks of initiation of lamotrigine. The patient was admitted to the hospital and Lamotrigine was taken off. Patient was given conservative management. Adverse drug reaction was reported to Adverse drug reaction monitoring centre (AMC) and severity was assessed by WHO-UMC Scale. Patient died after 5 days of admission. Score of Toxic epidermal necrolysis (SCORTEN Scale) is used to assess severity of the illness and to predict mortality rate. Early Diagnosis, withdrawal of offending agent, timely proper supportive management can help in lowering the mortality. Keywords: Toxic epidermal necrolysis, Lamotrigine, Adverse drug reaction, Multiple somatoform disorder, Steven Johnson Syndrome, Score of Toxic epidermal necrolysis

Association of thrombocytopenia with immune checkpoint inhibitors: a large-scale pharmacovigilance analysis based on the data from FDA adverse event reporting system database.

Introduction: An increasing number of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been reported during clinical treatment. We aimed to explore the clinical characteristics of patients with ICIs-induced ITP under different therapeutic strategies based on the FAERS database and explore the potential biological mechanisms in combination with TCGA pan-cancer data. Methods: Data from FAERS were collected for ICIs adverse reactions between January 2012 and December 2022. Disproportionality analysis identified ICIs-induced ITP in the FAERS database using the reporting odds ratio (ROR), proportional reporting ratio (PRP), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker algorithms (MGPS). The potential biological mechanisms underlying ITP induced by ICIs were examined using TCGA transcriptome data on cancers. Results: In the FAERS, 345 ICIs-induced ITP reports were retrieved, wherein 290 (84.06%) and 55 (15.94%) were reported as monotherapy and combination therapy, respectively. The median age of the reported patients with ICIs-induced ITP was 69 years (IQR 60-76), of which 62 (18%) died and 47 (13.6%) had a life-threatening outcome. The majority of reported indications were lung, skin, and bladder cancers, and the median time to ITP after dosing was 42 days (IQR 17-135), with 64 patients (43.5%) experiencing ITP within 30 days of dosing and 88 patients experiencing ITP in less than 2months (59.9%). The occurrence of ICIs-induced ITP may be associated with ICIs-induced dysregulation of the mTORC1 signaling pathway and megakaryocyte dysfunction. Conclusion: There were significant reporting signals for ITP with nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab/ipilimumab, and pembrolizumab/ipilimumab. Patients treated with anti-PD-1 in combination with anti-CTLA-4 are more likely to have an increased risk of ICIs-induced ITP. Patients with melanoma are at a higher risk of developing ITP when treated with ICI and should be closely monitored for this risk within 60 days of treatment. The potential biological mechanism of ICIs-induced ITP may be related to the dysfunction of megakaryocyte autophagy through the overactivation of the mTOR-related signaling pathway. This study provides a comprehensive understanding of ICIs-induced ITP. Clinicians should pay attention to this potentially fatal adverse reaction.

Evidence for sodium valproate toxicity in mitochondrial diseases: a systematic analysis

BackgroundWe aimed to determine whether sodium valproate (VPA) should be contraindicated in all mitochondrial diseases, due to known VPA-induced severe hepatotoxicity in some mitochondrial diseases.MethodsWe systematically reviewed the published literature...

Knowledge, Attitude, and Perception regarding antibiotic use and its associated resistance among the general public in Lahore, Pakistan.

BACKGROUND &amp; OBJECTIVE: Increasing misuse and irrational prescribing of antibiotics by physicians has led to antimicrobial resistance (AMR) posing a major global threat. Furthermore, only a few studies have been conducted to evaluate this domain in Pakistan. The objective of this study is to assess the general public’s knowledge, attitude, and perception towards antibiotic use and its resistance, and to determine positive associations between the various socio-demographic variables. METHODOLOGY: A descriptive cross-sectional study was conducted from October 2022 to March 2023. A convenient sampling technique was employed, selecting participants ≥ 18 years of age (n= 339). Structured questionnaires were distributed on different study sites and random participants were asked to respond immediately. RESULTS: Results showed that assessing antibiotics use among these 342 participants in the last year, it was determined that the majority of them had only used antibiotics once 108(31.6%). A closer number of individuals had used antibiotics more than thrice 101(29.5%) shows no significant association between rural and urban with a p-value=0.941&gt;0.05. The majority were also aware of fatal allergic reactions produced by some antibiotics and agreed to stop antibiotic use if any adverse reaction were to occur 277(81.0%)p-value=0.674&gt;0.05. No significance was observed, although some near-significant values of importance were noted and discussed. CONCLUSION: Antibiotic usage is commonly observed among all individuals; however, views contain many deviations. Constraints, including sample bias, Lahore’s urban dominance, and the omission of doctor-prescribing evaluations, highlight the study's limitations and have further skewed our results.

Impact of asthma on severe food-induced allergic reactions: a systematic review and meta-analysis.

Background. Food allergy can range from mild to severe, life-threatening reactions with various symptoms and organ involvement. The impact of asthma on severe food-induced allergic reactions is not completely understood. In the hypothesis that asthma increases the risk of severe food-induced allergic reactions, the aim of this study is to compare the incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma. Methods. We performed a systematic research on electronic databases, including PubMed, Scopus, and Web of Science. Observational studies, studies reporting medical characteristics of patients diagnosed with food allergy, and studies reporting medical history of patients with allergic reactions were included. The primary outcome was the incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma. The protocol of this review was registered in PROSPERO (CRD42023448293). Results. Eight studies with a total of 90,367 patients met the inclusion criteria and were included, with a total population of 28,166 of patients with food allergy. The incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma was increased (OR = 1.28; 95% CI 1.03-1.59; p = 0.03; I2 = 59%). Conclusions. Individuals with both food allergy and asthma are at high risk of severe, potentially fatal allergic reactions. Healthcare professionals should prioritize prevention and management strategies for these subjects.

Immune checkpoint inhibitor associated epidermal necrosis, beyond SJS and TEN: a review of 98 cases.

Immune checkpoint inhibitor (ICI) therapies carry the risk of major immune-related adverse events (irAEs). Among the most severe irAEs is epidermal necrosis that may clinically mimic Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The aim of this study was to provide a summary of the clinical and histological features of ICI-associated epidermal necrosis, with a special focus on factors associated with fatal outcomes in cases of extensive disease. A total of 98 cases, 2 new cases and 96 reported on PubMed and in the literature, of ICI-associated epidermal necrosis were assessed. Development of epidermal necrosis occurred between 1day and 3 years after starting ICI therapy, with an average onset of 13.8 weeks for patients with limited (< 30% BSA) and 11.3 weeks for those with extensive (≥ 30% BSA) involvement, and a median onset of 5.8 weeks and 4 weeks respectively. A preceding rash was seen in 52 cases and was more common in extensive cases. Mucosal involvement was only reported in 65% of extensive cases but was significantly associated with fatal reactions. Co-administration of cytotoxic chemotherapy was associated with more extensive disease. Recovery was observed in 96% and 65% of those with limited and extensive involvement respectively and no specific therapy was associated with improved survival. Young age was significantly associated with poor outcomes in extensive disease, the average age of surviving patients was 64.5 years old versus 55.1 years old for deceased patients, p < 0.01. Both superficial perivascular and interface/lichenoid inflammatory infiltrates were commonly seen. These findings suggest that ICI-associated epidermal necrosis should be considered a distinct clinical entity from drug-induced SJS/TEN.

Short developmental milestone risk assessment tool to identify Duchenne muscular dystrophy in primary care

BackgroundIn patients without a family history, Duchenne muscular dystrophy (DMD) is typically diagnosed at around 4–5 years of age. It is important to diagnose DMD during infancy or toddler stage in order to have timely access to treatment, opportunities for reproductive options, prevention of potential fatal reactions to inhaled anesthetics, awareness of a child’s abilities needed for good parenting, and opportunities for enrolment in clinical trials.MethodWe aimed to develop a short risk assessment tool based on developmental milestones that may contribute to the early detection of boys with DMD in primary care. As part of the case-control 4D-DMD study (Detection by Developmental Delay in Dutch boys with DMD), data on developmental milestones, symptoms and therapies for 76 boys with DMD and 12,414 boys from a control group were extracted from the health records of youth health care services and questionnaires. Multiple imputation, diagnostic validity and pooled backward logistic regression analyses with DMD (yes/no) as the dependent variable and attainment of 26 milestones until 36 months of age (yes/no) as the independent variable were performed. Descriptive statistics on symptoms and therapies were provided.ResultsA tool with seven milestones assessed at specific ages between 12 and 36 months resulted in a sensitivity of 79% (95CI:67–88%), a specificity of 95.8% (95%CI:95.3–96.2), and a positive predictive value of 1:268 boys. Boys with DMD often had symptoms (e.g. 43% had calf muscle pseudohypertrophy) and were referred to therapy (e.g. 59% for physical therapy) before diagnosis.DiscussionThis tool followed by the examination of other DMD-related symptoms could be used by youth health care professionals during day-to-day health assessments in the general population to flag children who require further action.ConclusionsThe majority of boys (79%) with DMD can be identified between 12 and 36 months of age with this tool. It increases the initial a priori risk of DMD from 1 in 5,000 to approximately 1 in 268 boys. We expect that other neuromuscular disorders and disabilities can also be found with this tool.

Immediate hypersensitivity reactions to iodinated contrast media despite drug prophylaxis-a comparative retrospective cohort study of breakthrough reactions in Bern (Switzerland) and Seoul (South Korea).

Although several studies deal with breakthrough reactions (BTRs) in patients with contrast media (CM) hypersensitivity reactions, the phenomenon is still unclear. Therefore, this study aimed to analyse in depth patients with BTR in two countries. We retrospectively analysed the electronic medical records of in- and outpatients (random sample enrolment) from two academic hospitals of tertiary care (Seoul/South Korea, with a special monitoring system exclusively for CM hypersensitivity, and Bern/Switzerland, manually operated) with respect to basic epidemiological data, number of BTRs per patient, and severity grades of severity in follow-up analyses. The study period lasted from 2013 (2000 Bern) to 2017. We identified 445 BTR-patients (91.5% from Seoul) with 691 BTRs (94.5% from Seoul). Most reactions were mild, 11% moderate and 3.9% severe. In Seoul, we found patients with up to 10 BTRs, and in Bern, there were only patients with one BTR. Fatal reactions or deaths did not occur. In most cases, the severity of the BTRs and of the index reactions were identical (80.8%). Mild index reactions remained constant in 90.6%. In contrast, in moderate index reactions the severity decreased/remained identically in 86.8% and increased in 13.2%. In severe index reactions, 55.6% of BTR reactions were severe again, in 44.4% the severity decreased. In 158 BTRs (22.9%) the culprit iodinated contrast medium (ICM) of the index reaction induced the BTR. In the other 482 BTRs (69.8%) the culprit ICM was changed to another non-culprit ICM. To the best of our knowledge, this is the largest study on patients with BTRs, and the first study showing BTRs in two centers in two countries of two continents. The main differences between the two centers result from the different hospital size, the number of patients, and the different documentation [manual (Bern) vs. electronical screening (Seoul)]. BTRs are no contraindications for further ICM-application. We recommend performing an allergy skin test as basis for the decision-making process of the next contrast-enhanced image-guided examination.

Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood.

Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics and prevent ABO-mismatched transfusions. The gut symbiont Akkermansia muciniphila can degrade mucin O-glycans including ABO epitopes. Here we biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions. Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analyses of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module. This study demonstrates the potential utility of mucin-degrading gut bacteria as valuable sources of enzymes for production of universal blood for transfusions.

Drug reaction with eosinophilia and systemic symptoms (DRESS) caused by sulfasalazine: a case report and literature review

Drug-induced hypersensitivity syndrome (DIHS) or drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially fatal systemic reaction characterized by multiorgan damage involving the liver, hematopoietic system and skin, and heterogeneous manifestations of fever, rash, lymphadenopathy and eosinophilia with unpredictable course.We describe a 41-year-old female patient who developed DRESS syndrome after taking sulfasalazine prescribed for non-radiographic axial spondyloarthritis. Treatment with intravenous and then oral glucocorticoids was effective. A review of the literature on this topic is presented.