Diagnosis of Hereditary TTP Caused by Homozygosity for a Rare Complex ADAMTS13 Allele After Salmonella Infection in a 43-Year-Old Asylum Seeker
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ABSTRACT:
SUBMITTER: Wendt R
PROVIDER: S-EPMC7959797 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
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Project description:With timely and effective treatment, most patients with thrombotic thrombocytopenic purpura (TTP) survive the acute TTP episode. In addition to the risk of relapse, TTP survivors have higher all-cause mortality than the general population and increased rates of chronic morbidities, including hypertension, depression, and mild cognitive impairment. We conducted this retrospective-prospective cohort study to determine the incidence and prevalence of stroke after recovery from acute TTP and to test the hypothesis that lower ADAMTS13 activity after recovery from TTP is associated with an increased risk of stroke during remission. Of 170 consecutive patients treated for TTP at The Johns Hopkins Hospital from 1995 through 2018, 14 (8.2%) died during the index episode and 19 were observed for less than 1 month after recovery. Of the remaining 137 patients, 18 (13.1%) developed stroke unrelated to an acute TTP episode over a median observation period of 3.08 years, which is fivefold higher than the expected prevalence of 2.6% from an age- and sex-matched reference population (P = .002). ADAMTS13 activity during remission was measured in 52 patients and was >70% in 44.2%, 40% to 70% in 23.1%, 10% to 39% in 25%, and <10% in 7.7%. Stroke after recovery from acute TTP occurred in 0% (0 of 22) of patients with normal remission ADAMTS13 activity (>70%) and in 27.6% (8 of 29) of patients with low ADAMTS13 activity (?70%; P = .007). In conclusion, stroke is common after recovery from TTP and is associated with reduced ADAMTS13 activity during remission.
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Project description:This study sought correlates of relapse tendency in TTP by examining gene expression profiles in peripheral blood leukocytes from patients with acquired ADAMTS13-deficient TTP in remission and matched healthy controls for global gene expression and autoantibodies.
2013-03-07 | GSE36418 | GEO
Project description:This study sought correlates of relapse tendency in TTP by examining gene expression profiles in peripheral blood leukocytes from patients with acquired ADAMTS13-deficient TTP in remission and matched healthy controls for global gene expression and autoantibodies. Total RNA was isolated from PAXgene RNA tubes from 39 patients with with acquired ADAMTS13-deficient TTP (all patients had relapsed) and 39 healthy controls.
2013-03-07 | E-GEOD-36418 | biostudies-arrayexpress
Project description:Asylum seekers frequently experience potentially traumatic events (PTEs), but the type and frequency vary depending on the country of origin. The cumulative effect of multiple PTEs and other stressors expose asylum seekers to a significant risk of mental ill health. The aim of the study was to examine the prevalence of PTEs, depression and anxiety symptoms, risk for psychological trauma, psychotropic medication use and previous mental health diagnoses among adult asylum seekers in the Asylum Seekers Health and Wellbeing (TERTTU) Survey (n = 784 respondents, participation rate 78.6%). A substantial majority (88.7%, 95% CI 86.9-90.3) of asylum seekers reported one or more PTEs before arriving to Finland. PTEs during the asylum-seeking journey were reported at 12.0% (95% CI 10.7-13.4), however, when examined by region of origin, the proportion was 34.5% (95% CI 29.5-39.8) for asylum seekers from Africa (excluding North Africa). Significant symptoms of depression were reported by 41.7% (95% CI 39.6-43.9) of asylum seekers and symptoms of anxiety by 34.2% (95% CI 32.1-36.2). Half of the asylum seekers were assessed as having at least a medium-risk for psychological trauma. Prevalence rates were higher among females and asylum seekers from Africa. This study highlights the importance of using screening tools to identify asylum seekers with severe mental health problems that may need referral to further assessment and treatment. Asylum seekers from Africa (excluding North Africa) should be given additional attention in initial health screenings and examinations.
| S-EPMC8297147 | biostudies-literature
Project description:Primary hyperoxaluria (PH) Type 1 is a rare, genetic disorder caused by deficiency of the liver enzyme alanine-glyoxylate aminotransferase, which is encoded by AGXT gene. We report a 2-year-old South Indian Tamil child with nephrocalcinosis due to PH Type 1, in whom a homozygous genotype for two missense mutations in the AGXT gene was found: first, a C to G transversion (c. 32C>G) in exon 1 resulting in the amino acid substitution p.Pro11Arg; second, a T to A transversion (c. 167T>A) in exon 2 resulting in p.Ile56Asn. A therapy based on potassium citrate and pyridoxine was started. This is the first report of molecular testing-proven childhood onset-PH Type 1 from South India and is notable for the co-occurrence of two missense mutations in one AGXT allele, which might lead to different and more severe phenotype than each mutation alone. To the best of our knowledge, AGXT allele carrying two already known mutations has not been previously reported.
| S-EPMC5590421 | biostudies-literature
Project description:Purpose: The coronavirus disease 2019 (COVID-19) pandemic presents health care challenges to asylum seekers living in congregate encampments, including those along the U.S.-Mexico border. It is necessary to understand the impact of the pandemic among this population to address health care needs, reduce transmission, and diminish COVID-19-related morbidity. Methods: Thirty interviews were conducted with asylum seekers and health care professionals in a temporary camp in Matamoros, Mexico to determine challenges, perceptions, and effects of the COVID-19 pandemic. Interviews were coded in NVivo12 by using a team-based approach. Results: The pandemic caused significant mental health burdens but no perceived adverse physical effects, with the U.S. border closure and health care access barriers as more pressing concerns. Participants reported access to information about COVID-19 but had varied levels of knowledge and adherence to disease reduction strategies due to camp conditions. Most participants believed that they had special protection from COVID-19, including strong immune systems or from God. The nongovernmental organizations providing health care and sanitation faced multiple challenges to implement new policies to manage COVID-19. The institution of required temperature checks and quarantine of COVID-19 positive patients led to distrust, decreased seeking of health care services among asylum seekers, and possible underreporting of COVID-19 cases. Conclusion: Our findings among asylum seekers in a Matamoros camp highlight the challenges to implementing disease reduction policies in low-resource congregate camps. Policies to address disease outbreaks focusing on the social determinants of health, health care access barriers, and community engagement may be more acceptable to asylum seekers, suggesting the need for effective strategies to provide prevention information that complements such measures.
| S-EPMC8080921 | biostudies-literature
Project description:Absent or severely diminished activity of ADAMTS13 (A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13) resulting in the intravascular persistence and accumulation of highly thrombogenic ultra large von Willebrand factor (UL-VWF) multimers is the pathophysiological mechanism underlying thrombotic thrombocytopenic purpura. Reduced VWF-cleaving protease levels, however, are not uniquely restricted to primary thrombotic microangiopathy (TMA), e.?g. thrombotic thrombocytopenic purpura, but also occur in other life-threatening thrombocytopenic conditions: severely decreased ADAMTS13 activity is seen in severe sepsis, disseminated intravascular coagulation (DIC) and complicated malarial infection. The clinical relevance of these secondary thrombotic microangiopathies is increasingly recognised, but its therapeutic implications have not yet been determined. The presence of a secondary TMA in certain diseases may define patient groups which possibly could benefit from ADAMTS13 replacement or a VWF-targeting therapy. This short-review focuses on the role of UL-VWF multimers in secondary TMA and discusses the potential of investigational therapies as candidates for the treatment of TTP. In conclusion, prospective clinical trials on the effectiveness of protease replacementin vivo seem reasonable. Carefully selected patients with secondary TMA may benefit from therapies primarily intended for the use in patients with TTP.
| S-EPMC4745134 | biostudies-literature
Project description:Infection or inflammation may precede and trigger formation of microvascular thrombosis in patients with acquired thrombotic thrombocytopenic purpura (TTP). However, the mechanism underlying this clinical observation is not fully understood. Here, we show that human neutrophil peptides (HNPs) released from activated and degranulated neutrophils inhibit proteolytic cleavage of von Willebrand factor (VWF) by ADAMTS13 in a concentration-dependent manner. Half-maximal inhibitory concentrations of native HNPs toward ADAMTS13-mediated proteolysis of peptidyl VWF73 and multimeric VWF are 3.5 μM and 45 μM, respectively. Inhibitory activity of HNPs depends on the RRY motif that is shared by the spacer domain of ADAMTS13. Native HNPs bind to VWF73 (KD = 0.72 μM), soluble VWF (KD = 0.58 μM), and ultra-large VWF on endothelial cells. Enzyme-linked immunosorbent assay (ELISA) demonstrates markedly increased plasma HNPs1-3 in most patients with acquired autoimmune TTP at presentation (median, ∼170 ng/mL; range, 58-3570; n = 19) compared with healthy controls (median, ∼23 ng/mL; range, 6-44; n = 18) (P < .0001). Liquid chromatography plus tandem mass spectrometry (LC-MS/MS) reveals statistically significant increases of HNP1, HNP2, and HNP3 in patient samples (all P values <.001). There is a good correlation between measurement of HNPs1-3 by ELISA and by LC-MS/MS (Spearman ρ = 0.7932, P < .0001). Together, these results demonstrate that HNPs1-3 may be potent inhibitors of ADAMTS13 activity, likely by binding to the central A2 domain of VWF and physically blocking ADAMTS13 binding. Our findings may provide a novel link between inflammation/infection and the onset of microvascular thrombosis in acquired TTP and potentially other immune thrombotic disorders.
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Project description:This article describes how one trial site of the Refugee Emergency: Defining and Implementing Novel Evidence-based psychosocial interventions (RE-DEFINE) study, designed to evaluate a Self Help+ intervention with Arabic-speaking refugees and asylum seekers currently living in the UK and experiencing stress, was adapted to accommodate social distancing rules and working from home during the COVID-19 restrictions. Digital divide, risk and safety management, acceptability of remote data collection and practical considerations are described. The adaptions to methods have practical implications for researchers looking for more flexible approaches in response to continuing restrictions resulting from COVID-19, and the authors believe that others could adopt such an approach. The need for a further acceptability study focusing on human and economic costs and benefits of telephone and video as an alternative to face-to-face data collection is indicated. TRIALS REGISTRATION: Refugee Emergency - Defining and Implementing Novel Evidence-based psychosocial interventions RE-DEFINE. (Trials registration numbers NCT03571347 , NCT03587896 ) https://doi.org/10.1136/bmjopen-2019-030259 (2019).
| S-EPMC7863031 | biostudies-literature
Project description:BackgroundTemporal patterns in the frequency and characteristics of self-harm episodes across the Australian asylum seeker population may have implications for self-harm prevention and public health policy. The aim of this study was to examine how the distribution of self-harm episodes and method(s) of self-harm used across the Australian asylum seeker population vary according to the 24-hour cycle, day, and month, and to establish a basis for further research.Methods and findingsWe conducted an observational study of all 949 self-harm incidents reported across the Australian asylum seeker population (representing a monthly average of 28,992 adults) between 1 August 2014 and 31 July 2015, obtained by Freedom of Information (FOI) from the Department of Immigration. Time of self-harm, day, and month of occurrence were investigated across all five Australian asylum seeker populations (i.e., community-based arrangements, community detention, onshore immigration detention, offshore immigration detention [Nauru], and offshore immigration detention [Manus Island]). Significant variations in distributions over the 24-hour cycle were observed by processing arrangements. Compared with the average distribution across all other processing arrangements, self-harm more commonly occurred among community-based asylum seekers (36.3%) between 12:00 AM and 3:59 AM (p < 0.001), in asylum seekers on Manus Island (36.4%) between 4:00 PM and 7:59 PM (p = 0.02), and among asylum seekers in onshore detention (20.4%) between 8:00 PM and 11:59 PM (p < 0.001). Compared with the average distribution across all other methods, self-poisoning (by medication) (25%) was significantly more likely to occur between 12:00 AM and 3:59 AM (p = 0.009), and self-battery (42%) between 8:00 AM and 11:59 AM (p < 0.001). The highest and lowest monthly self-harm episode rates for the whole asylum seeker population were in August (2014) (5 episodes per 1,000 asylum seekers; 95% confidence interval [CI] 1-11) and in both January and February (2015) (2.1 episodes per 1,000 asylum seekers; 95% CI 0.6-7.2), respectively; however, the overlapping CIs indicate no statistically significant differences across the months. When examining monthly trends by processing arrangements, we observed that self-harm was significantly more likely to occur in August (2014) than other months of the year among asylum seekers in onshore detention (19%) (p < 0.001), in January (2015) on Manus Island (18%) (p = 0.002), and in October (2014) on Nauru (15%) (p < 0.001). The main study limitations were that we could not investigate certain characteristics associated with self-harm (e.g., gender, country of origin), as the Department of Immigration did not routinely collect such data. There was also the potential risk of making a type 1 error, given the exploratory nature of the comparisons we undertook; we minimised this by lowering our significance threshold from 0.05 to 0.01.ConclusionsSelf-harm in the Australian asylum seeker population was found to vary according to time of day and month of the year, by processing arrangements. A series of procedure-related and detention-related factors were observed to be associated with the temporal variations in self-harm. These findings should form the basis for further investigation into temporal variations in self-harm among asylum seekers, which may in turn lead to effective self-harm prevention strategies.
| S-EPMC7410206 | biostudies-literature