Positive Test Research Articles

Risk factors for and timing of presumptive recurrent TB.

<sec><title>INTRODUCTION</title>Understanding factors associated with increased risk for tuberculosis (TB) recurrence is essential in lowering the TB burden. We aimed to quantify the burden, risk factors, and timing of TB presumptive recurrence.</sec><sec><title>METHODS</title>We analyzed test results from 2013 to 2017 in the South African National Health Laboratory Service's database. We defined a person's TB episode to start with their first positive TB test. In the absence of treatment outcome data, we assumed the episode concluded 6 months later for rifampicin-susceptible TB (RS-TB) and 18 months later for rifampicin-resistant TB (RR-TB), provided that at least one negative smear or culture test was recorded within this period. We defined a presumptive recurrent TB episode to start with a positive TB test after the completion of a prior episode. We calculated recurrence measures stratified by various demographics and RR-TB status.</sec><sec><title>RESULTS</title>Of 574,316 people with RS-TB, 4.7% experienced at least one presumptive recurrent TB episode. Higher local TB notification rates, HIV coinfection, and males experienced higher recurrence rates. Most (89.4%) of the first RS-TB recurrences occurred within a year of the initial episode.</sec><sec><title>CONCLUSION</title>Our findings of when and among whom recurrent TB is more likely to occur can be used to assist early interventions and inform impact on patient care.</sec>.

Results of patch testing propolis in the European baseline series: A 4-year retrospective study.

Propolis was added to the European baseline series (EBS) in 2019. To investigate the frequency and relevance of positive patch tests to propolis in the EBS and to study co-reactivities. Retrospective study in patients patch tested between June 2019 and November 2023 in a university hospital in Amsterdam, The Netherlands. Of 3134 consecutive patients, 299 (9.5%) had a positive reaction to propolis 10% pet. Only nine reactions (3%) were judged to be clinically relevant. There were significant co-reactivities to Myroxylon pereirae resin (balsam of Peru), colophonium, fragrance mixes 1 and 2, and to limonene and linalool hydroperoxides. A steep increase in rates of positive reactions to propolis was observed from 2020 to 2023. This was highly likely the result of the replacement of Chinese propolis with Brazilian propolis by the manufacturer. Positive patch tests for propolis are very frequent in Amsterdam, but only a few of these reactions are relevant. Most are probably (pseudo-)cross-reactions in patients with fragrance allergies. Propolis in the EBS has very limited value for dermatologists and patients in The Netherlands. Changes in patch test materials should be provided to all users to avoid misinterpretation of patch test results.

Characteristics of Fungal Monosensitization in Turkey

Study ObjectiveFungi are recognized as allergenic sources and may play a role in the development, persistency, and severity of allergic diseases. Alternaria, Cladosporium, Penicillium, and Aspergillus, which belong to the Phylum Ascomycota, are well-characterized four genera among fungi species. To our knowledge, there is not enough data about monosensitization to fungi. We aimed to investigate the characteristics of monosensitized patients to fungal allergens. Patients-MethodsSixty-seven adult patients, who had a positive skin prick test reaction with fungal allergen out of a total of 4200 SPT results performed between January 2015 and June 2022 in two tertiary centers were included in the study. The clinical data of the patients were obtained retrospectively from the hospital medical records. ResultsFifty-six (83.6%) patients were sensitized to one type of fungal allergen (Female/Male: 38/18) and eleven (16.4%) (Female/Male: 9/2) were sensitized to two types of fungi. Aspergillus was the most prevalent fungal allergen, followed by Cladosporium and Alternaria. Allergic rhinitis was the most common allergic disease. ConclusionMonosensitization to fungal allergens is rare. Monosensitization to at least one fungal allergen may lead to significant allergic diseases by potentially impacting the immune system.

The effect of BCG revaccination on the response to unrelated vaccines in urban Ugandan adolescents (POPVAC C): an open-label, randomised controlled trial

Immune responses induced by several important vaccines differ between populations, with reduced responses in low-income and rural settings compared with high-income and urban settings. BCG immunisation boosts immune responses to some unrelated vaccines in high-income populations. We aimed to test the hypothesis that BCG revaccination can enhance responses to unrelated vaccines in Ugandan schoolchildren. We conducted an open-label, randomised controlled trial to compare the effects of BCG revaccination versus no BCG revaccination on the immunogenicity of subsequent unrelated vaccines among adolescents aged 13-17 years who are participants in an urban Ugandan birth cohort study, in which BCG vaccination was documented at birth. Participants were excluded if they had received any of the trial vaccines or related agents when aged 5 years or older. Computer-generated 1:1 randomisation was implemented in REDCap. Participants were excluded if they were concurrently enrolled in other trials; had a clinically significant history of immunodeficiency, or serious psychiatric conditions or moderate to severe acute illnesses; were taking immunosuppressive medications; had allergies to vaccine components, a predisposition towards developing keloid scarring; positive HIV tests or pregnancy tests; were female participants who were lactating; or if they planned to use investigational drugs, vaccines, blood products, or any combination thereof. Trial participants assigned to the BCG revaccination group received the live parenteral BCG-Russia vaccine (Serum Institute of India, Pune, India; 0·1 mL intradermally, right upper arm) at week 0. All participants received yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France; 0·5 mL intramuscularly, left upper arm), live oral typhoid vaccine (Ty21a; PaxVax, London, UK; one capsule per day taken for three alternate days), and quadrivalent virus-like particle human papillomavirus (HPV) vaccine (Merck, Rahway, NJ, USA; 0·5 mL intramuscularly, left upper arm) at week 4; and toxoid vaccines (tetanus-diphtheria; Serum Institute of India; 0·5 mL intramuscularly, left upper arm) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated. The primary outcomes were yellow fever neutralising antibody titres at 4 weeks post-YF-17D vaccination, Salmonella enterica serovar Typhi (henceforth S Typhi) O-lipopolysaccharide (O:LPS)-specific IgG concentration at 4 weeks post-Ty21a vaccination, and HPV-16 and HPV-18 L1 protein-specific IgG concentration at 4 weeks post-HPV vaccination. Primary outcome assays were conducted at week 8, and at week 52 for tetanus-diphtheria. We conducted an intention-to-treat analysis comparing log-transformed outcomes between trial groups, with results back-transformed to geometric mean ratios (GMRs). The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN10482904) and is complete. Between Aug 31 and Oct 12, 2020, we screened 376 potential participants for eligibility. We enrolled and randomly allocated 300 participants to the two groups (151 [50%] to the BCG group and 149 [50%] to the no BCG group). 178 (59%) of 300 participants were male and 122 (41%) were female. 142 (91%) of 151 participants in the BCG group and 139 (93%) of 149 in the no BCG group completed follow-up. There was no effect of BCG revaccination, compared with no BCG revaccination, on the response observed for any vaccine. Yellow fever plaque reduction neutralising reference tests (PRNT50) titres (the reciprocal of the last plasma dilution that reduced by 50%) had a GMR of 0·95 (95% CI 0·75-1·19; p=0·62) and PRNT90 (reciprocal of the last plasma dilution that reduced by 90%) had a GMR of 0·94 (0·74-1·19; p=0·60); IgG to S Typhi O:LPS was 0·99 (0·80-1·23; p=0·94); IgG to HPV-16 was 0·97 (0·69-1·35; p=0·85) and to HPV-18 was 1·03 (0·76-1·40; p=0·83); and toxoid-specific IgG for tetanus was 1·13 (0·87-1·47; p=0·36) and was 1·00 (0·87-1·16; p=0·97) for diphtheria. There were no serious adverse events in either group. We found no evidence that BCG revaccination is an effective strategy to improve immunogenicity of other vaccines in this low-income, urban setting. UK Medical Research Council. For the Luganda translation of the abstract see Supplementary Materials section.

COVID-19 testing and reporting behaviours in England across different sociodemographic groups: a population-based study using testing data and data from community prevalence surveillance surveys

Understanding underlying mechanisms of heterogeneity in test-seeking and reporting behaviour during an infectious disease outbreak can help to protect vulnerable populations and guide equity-driven interventions. The COVID-19 pandemic probably exerted different stresses on individuals in different sociodemographic groups and ensuring fair access to and usage of COVID-19 tests was a crucial element of England's testing programme. We aimed to investigate the relationship between sociodemographic factors and COVID-19 testing behaviours in England during the COVID-19 pandemic. We did a population-based study of COVID-19 testing behaviours with mass COVID-19 testing data for England and data from community prevalence surveillance surveys (REACT-1 and ONS-CIS) from Oct 1, 2020, to March 30, 2022. We used mass testing data for lateral flow device (LFD; data for approximately 290 million tests performed and reported) and PCR (data for approximately 107 million tests performed and returned from the laboratory) tests made available for the general public and provided by date and self-reported age and ethnicity at the lower tier local authority (LTLA) level. We also used publicly available data on mean population size estimates for individual LTLAs, and data on ethnic groups, age groups, and deprivation indices for LTLAs. We did not have access to REACT-1 or ONS-CIS prevalence data disaggregated by sex or gender. Using a mechanistic causal model to debias the PCR testing data, we obtained estimates of weekly SARS-CoV-2 prevalence by both self-reported ethnic groups and age groups for LTLAs in England. This approach to debiasing the PCR (or LFD) testing data also estimated a testing bias parameter defined as the odds of testing in infected versus not infected individuals, which would be close to zero if the likelihood of test seeking (or seeking and reporting) was the same regardless of infection status. With confirmatory PCR data, we estimated false positivity rates, sensitivity, specificity, and the rate of decline in detection probability subsequent to reporting a positive LFD for PCR tests by sociodemographic groups. We also estimated the daily incidence, allowing us to calculate the fraction of cases captured by the testing programme. From March, 2021 onwards, individuals in the most deprived regions reported approximately half as many LFD tests per capita as individuals in the least deprived areas (median ratio 0·50 [IQR 0·44-0·54]). During the period October, 2020, to June, 2021, PCR testing patterns showed the opposite trend, with individuals in the most deprived areas performing almost double the number of PCR tests per capita than those in the least deprived areas (1·8 [1·7-1·9]). Infection prevalences in Asian or Asian British individuals were considerably higher than those of other ethnic groups during the alpha (B.1.1.7) and omicron (B.1.1.529) BA.1 waves. Our estimates indicate that the England Pillar 2 COVID-19 testing programme detected 26-40% of all cases (including asymptomatic cases) over the study period with no consistent differences by deprivation levels or ethnic groups. Testing biases for PCR were generally higher than those for LFDs, in line with the general policy of symptomatic and asymptomatic use of these tests. Deprivation and age were associated with testing biases on average; however, the uncertainty intervals overlapped across deprivation levels, although the age-specific patterns were more distinct. We also found that ethnic minorities and older individuals were less likely to use confirmatory PCR tests through most of the pandemic and that delays in reporting a positive LFD test were possibly longer in populations self-reporting as "Black; African; Black British or Caribbean". Differences in testing behaviours across sociodemographic groups might be reflective of the higher costs of self-isolation to vulnerable populations, differences in test accessibility, differences in digital literacy, and differing perceptions about the utility of tests and risks posed by infection. This study shows how mass testing data can be used in conjunction with surveillance surveys to identify gaps in the uptake of public health interventions both at fine-scale levels and across sociodemographic groups. It provides a framework for monitoring local interventions and yields valuable lessons for policy makers in ensuring an equitable response to future pandemics. UK Health Security Agency.

Allergies aux fientes d’oiseaux

The problems of human–bird cohabitation are not a recent phenomenon even if today their importance has taken on an indisputable extent. Their droppings contain significant concentrations of microorganisms and can cause allergic diseases, such as hypersensitivity pneumonitis (HSP), formerly called extrinsic allergic alveolitis, but also rhinitis, asthma or conjunctivitis. We report a rare case of allergy to bird droppings in a patient who raises chickens and canaries, having consulted for rhinoconjunctivitis whose allergological assessment found sensitization of these droppings with positive skin and specific IgE tests. Its management consisted of avoiding the risk with medical treatment. It is a rare pathology that must be considered in the event of exposure to birds.

Implementation and Performance of a Point-of-Care COVID-19 Test Program in 4,000 California Schools

To evaluate the feasibility and accuracy of an unprecedented COVID-19 antigen testing program in schools, which required a healthcare provider order, laboratory director, a Clinical Laboratory Improvement Amendments certificate of waiver, as well as training of school personnel. Descriptive report of a point-of-care, school-based antigen testing program in California from August 1st, 2021 through May 30, 2022, in which participants grades K-12 self-swabbed and school personnel performed testing. Participants included 944 009 students, personnel, and community members from 4022 California kindergarten through high schools. Outcomes measured include sensitivity and specificity (with polymerase chain reaction [PCR] as comparator) of the Abbott BinaxNOW antigen test, number of tests performed, and active infections identified. Of 102 022 paired PCR/antigen tests, the overall sensitivity and specificity for the antigen test was 81.2% (95% CI: 80.5%-81.8%) and 99.6% (95% CI: 99.5%-99.6%), respectively, using cycle threshold values<30. During January through March 2022, the highest prevalence period, the positive predictive value of antigen testing was 94.7% and the negative predictive value was 94.2%. Overall, 4022 school sites were enrolled and 3 987 840 million antigen tests were performed on 944 009 individuals. A total of 162 927 positive antigen tests were reported in 135 163 individuals (14.3% of persons tested). Rapidly implementing a school-based testing program in thousands of schools is feasible. Self-swabbing and testing by school personnel can yield accurate results. On-site COVID-19 testing is no longer necessary in schools, but this model provides a framework for future infectious disease threats.

CMV Retinitis in the Context of SARS-CoV-2 Infection: A Case Study and Comprehensive Review of Viral Interactions

Purpose: Cytomegalovirus (CMV) retinitis is a sight-threatening condition predominantly affecting immunocompromised individuals, such as those with Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS). We aimed to present an observational case report on CMV retinitis following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and to review the literature on the molecular and cellular changes in CMV and SARS-CoV-2 infections and how they may influence each other. Case Description: A 32-year-old man with a history of AIDS presented with decreased vision and ocular pain exacerbated by movement, beginning a day prior. Ocular examination revealed anterior uveitis, corneal endothelial edema, and retinal necrosis in the left eye. CMV retinitis was diagnosed based on positive serologic testing and a low cluster of differentiation 4 (CD4) count, with concurrent SARS-CoV-2 infection detected. Treatment included valganciclovir and topical agents, with a focus on managing CMV complications. This case highlights the potential role of SARS-CoV-2 in reactivating dormant CMV in severely immunocompromised individuals. We also discuss the implications of this interaction for immunocompromised patients, emphasizing the need for vigilant monitoring and personalized treatment strategies. Conclusions: Our case suggests that SARS-CoV-2 may trigger reactivation of CMV infection, leading to bilateral involvement in patients with low CD4 lymphocyte counts, which can result in severe visual impairment. The review discusses the molecular and cellular interactions between CMV and SARS-CoV-2, as well as risk factors, pathophysiology, and diagnostic methods for CMV retinitis, providing recommendations based on the literature findings.

Recreational drugs use as prognostic factor of major adverse cardiovascular and cerebrovascular events in patients hospitalised for acute cardiovascular events

Abstract Background Among patients admitted to the intensive cardiac care unit (ICCU), systematic screening for recreational drugs evidenced a significant prevalence of recent use and was associated with a higher rate in-hospital outcomes. However, long-term cardiovascular consequences of recreational drug use remain uncertain. Purpose We aimed to evaluate the prognostic impact of recreational drugs use at 1-year follow-up to predict major adverse cardiovascular and cerebrovascular events (MACCE) in consecutive patients admitted to ICCUs for acute cardiovascular events from the Addiction in Intensive Cardiac Care Units (ADDICT-ICCU) study. Methods In this prospective multicentric study, all consecutive patients admitted to ICCUs over two weeks in April 2021 at 39 centres across France were included. Screening for recreational drugs use was performed by systematic urinary testing. One-year follow-up consisted of a clinical visit or direct contact with the patient and the referring cardiologist. The primary composite outcome was the occurrence of one of the combined MACCE defined as cardiovascular death, nonfatal myocardial infarction (MI) or stroke. Subgroup analysis was performed in patients hospitalised at baseline for acute coronary syndrome. Results Of the 1499 consecutive patients screened, 1392 (93%) patients (63±15 years, 70% males) had a complete 1-year follow-up. Among them, 157 (11%) had an initial positive test for recreational drug use (cannabis, opioids, cocaine, amphetamines, 3,4-methylenedioxymethamphetamine [MDMA]). After 1-year of follow, 94 (7%) patients experimented MACCE. Patients with positive testing exhibited a higher rate of MACCE than non-users (13% vs 6%, respectively, p=0.002). After adjustment for traditional prognosticators, recreational drug use was independently associated with the occurrence of MACCE (HR=2.99; 95% CI: 1.73-5.16, p&amp;lt;0.001). In the subgroup analysis of 713 patients hospitalised at baseline for acute coronary syndrome, 96 (14%) had a positive recreational drug test and 50 (7%) experienced MACCE. Using a multivariable Cox analysis in this population, recreational drug use was still independently associated with MACCE after adjustment for traditional prognosticators (HR=2.98; 95% CI: 1.43-6.21, p=0.004). Conclusions In a large cohort of consecutive patients admitted to ICCUs for acute cardiovascular events, the prevalence of recreational drug use was 11%. Recreational drug use was strongly associated with the occurrence of 1-year MACCE even after adjustment for traditional prognosticators.Central illustrationPrognostic impact of drug use

Diagnostic potential of relative changes in high-sensitivity troponin levels during intracoronary acetylcholine provocation testing

Abstract Background Intracoronary acetylcholine (ACh) provocation testing is useful for the diagnosis of vasospastic angina (VSA). However, the positive or negative diagnosis of ACh testing is often challenging when lacking typical anginal symptoms and electrocardiographic changes during provocation tests. We hypothesized that relative changes in cardiac troponin levels during ACh provocation testing may be suggestive of myocardial ischemia and would be helpful for the VSA diagnosis. Purpose To evaluate the diagnostic potential of relative changes in high sensitivity troponin I (hs-TnI) levels during intracoronary ACh provocation test. Methods This preliminary study included a total of 29 patients undergoing invasive coronary angiography with or without ACh provocation tests. Patients were divided into three groups; no ACh provocation tests (i.e. angiography alone), negative ACh tests, and positive ACh tests. Blood samples were obtained twice, before and after angiography, through the arterial sheath to evaluate hs-TnI. The primary measure was relative changes in hs-TnI (i.e. Δhs-TnI). Positive ACh provocation test was defined as total or subtotal coronary occlusion accompanied by chest pain and/or ischemic electrocardiographic changes. Results Of the 29 patients, 10 (34.5%) underwent coronary angiography alone, while ACh provocation testing was performed in 19 (65.5%) patients, of whom 7 (36.8%) and 12 (63.2%) had negative and positive ACh test results. Overall, the mean time interval between the blood sample collections was 76 minutes. Levels of hs-TnI before angiography did not differ significantly in the no, negative, and positive ACh test groups (5.3 [2.8, 8.6] vs. 2.9 [1.3, 8.8] vs. 3.3 [1.6, 8.5] pg/ml, p=0.76), while Δhs-TnI was highest in the positive ACh test group, followed by the negative and no ACh test groups (4.2 [0.5, 8.1] vs. 0.8 [0.4, 4.6] vs. −0.3 [−0.6, 0.3], p=0.002) (Figure). Conclusions In patients undergoing intracoronary ACh testing for the VSA diagnosis, a relative increase in Δhs-TnI during angiography was observed than in those who did not undergo the provocation tests, particularly when the ACh test diagnosis was positive. Our findings suggest that Δhs-TnI has the potential to aid in the positive or negative diagnosis of ACh provocation testing.

Enhancement of the Mayo Clinic Genotype Predictor Score using Cardiac MRI

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy typically transmitted in an autosomal dominant fashion. There is growing importance in identifying genetic test positive patients given its prognostic value. The Mayo HCM Genotype Predictor Score has been extensively validated for assessment of patient’s pre-test probability for genotype positive HCM and helps guide clinical decision-making based on clinical and echocardiographic variables. Herein, we evaluated the role of cardiac magnetic resonance (CMR) to enhance the genotype predictor score. Purpose Evaluate performance of the Mayo Clinic HCM Genotype Predictor Score using CMR variables, and develop an updated, CMR incorporated score. Methods Retrospective analysis was conducted on 175 unrelated HCM patients with at least 1 MRI and a HCM genetic testing seen at the Mayo Clinic between April 2004 and April 2018. Phenotyping information was obtained through review of electronic medical records. The original Mayo HCM Genotype Predictor Score was calculated using both echocardiography and clinical variables. An updated score was created incorporating CMR-specific variables. Diagnostic accuracy of the models was assessed thought Receiver Operating Characteristic (ROC) curves. Results Overall, 108 (62%) were males with a mean age at CMR of 51 ± 18 years. The yield of positive genetic test for the echocardiogram-derived Mayo HCM Genotype Predictor Score ranged from 38% for patients with -1 point to 100% for patients with 4 or 5 points. There was a significant incremental increase in diagnostic yield between score subgroups (p &amp;lt; 0.01) with an AUC of 0.659 (Figure 1A). Similar findings were observed using CMR variables (AUC of 0.697; Figure 1B). Univariate and multivariate analysis identified late gadolinium enhancement (LGE) as a strong predictor of a positive genetic test (OR 3.72; p=0.002), and it was added to the original score to create a new version. The Updated Mayo HCM Genotype Predictor Score predicted a positive genetic test ranging from 25% for patients with -1 point to 100% for patients with 5 or 6 points (p &amp;lt; 0.01). There was a significant increase in diagnostic accuracy when compared to the original score (AUC 0.724 vs 0.679; p=0.03; Figure 1C). Conclusion Using LGE, the updated CMR-based Mayo HCM Genotype Predictor score provides a simple and improved tool to aid in genetic counseling for HCM patients.

Improving the yield of genetic testing in dilated cardiomyopathy using late gadolinium enhancement

Abstract Background Genetic testing has become an important tool in the work-up of dilated cardiomyopathy (DCM), aiding in family screening and providing information about prognosis and arrhythmic risk. Nonetheless, a significant proportion of patients with DCM present negative genetic test results. The "Madrid Score" was created to evaluate the likelihood of positive genetic tests and increase their yield in DCM patients. Purpose To determine if late gadolinium enhancement (LGE) assessment can improve the Madrid Score accuracy and increase the yield of genetic tests for DCM. Methods A single-centre retrospective study of patients diagnosed with DCM who underwent cardiac magnetic resonance (CMR) and genetic test between January 2017 and October 2023. The CMR imaging included the assessment of LGE. Multivariate logistic regression was performed and the model’s change in performance was evaluated when adding LGE. Results A total of 90 patients with the diagnosis of DCM underwent CMR and genetic test during the study period. Patient’s mean age was 51.0±14.6 years, and 57.1% were male. The genetic test was positive (G+) in 42 (46.7%), and negative (G-) in 48 (53.3%) patients. A variant of uncertain significance was present in 31 (34.4%), and these were included in the G- group. Most of the known independent predictors of a G+ given by the Madrid Score were significant in our cohort: Family history of DCM (OR: 4.82; CI: 1.73-11.60; p &amp;lt; 0.001), absence of hypertension (OR: 0.19; CI: 0.06-0.58; p &amp;lt; 0.001), absence of left bundle branch block (OR: 0.22; CI: 0.05-0.98; p = 0.047), and low electrocardiogram voltage in peripheral leads (OR: 3.13; CI: 0.87-11.26; p = 0.081). When analyzing the effect of LGE in the regression model (R2 = 0.622, p &amp;lt; 0.001), we found that the number of LGE segments (OR: 2.54; CI: 1.10-5.90; p = 0.031), and the presence of LGE in the anterior wall (OR: 3.01; CI: 1.42-12.04; p = 0.041), were associated with a higher rate of positive genetic tests. When comparing both regression models, the incorporation of LGE increased the prediction power of the standard Madrid Score, correctly predicting 82.0% of the tests in our sample, with a probability of a G+ result ranging from 2% when all predictors were absent to 84% when ≥6 predictors, including LGE, were present. Conclusion Our study suggests that LGE assessment may enhance the Madrid Score performance and consequently improve genetic testing decisions in DCM, potentially leading to better use of the limited resources in our health care system.

Prognostic role of gene variants in sudden cardiac death risk associated to paediatric hypertrophic cardiomyopathy

Abstract Introduction Genetic testing plays an important role in diagnosis of hypertrophic cardiomyopathy (HCM), being sarcomeric genes commonly involved, particularly MYBPC3. However, arrhythmic risk related to genotype remains unclear in adults and almost unexplored in children. Hence, current sudden cardiac death (SCD) risk calculators do not include genetic information. Purpose To analyse risk of arrhythmic events associated with causal variants in MYBPC3 respecting to other genes in a paediatric cohort with non-syndromic HCM from a cardiomyopathy referral centre. Methods This retrospective study included patients with non-syndromic HCM 0-18 years old between 2009-2022. Demographic, clinical, and genetic data were collected. Genetic variants pathogenicity followed American College of Medical Genetics criteria. A positive genetic test was considered if a likely pathogenic or pathogenic variant in HCM related genes was found. Considered outcomes were SCD or a major arrhythmic cardiac event (MACE) within 5 years follow-up: recovered SCD, appropriate ICD therapy, or sustained ventricular tachycardia. Some SCD-risk estimation models (in 5 years) as HCM Risk-SCD model for patients &amp;gt;=15 y.o and/or 55 kg, ESC Guidelines paediatric algorithm, and HCM Risk-Kids model were applied. Results 77 patients were diagnosed with non-syndromic HCM. A causal variant was found in 45/73 (62%). No significant differences in cardiac phenotype were found related to genes. 10/77 patients (13%) presented a MACE in 5 years follow-up. A positive genetic study was significantly associated with having an event (p=0.011). Most patients with a positive genetic test harboured MYBPC3 variants (21/45, 47%), however only 2 patients who suffered a MACE had a causal variant in MYBPC3. Those with causal variants in genes other than MYBPC3 presented more and earlier events (p=0.022). Risk of having a MACE during follow-up was higher when presenting causal variants in genes other than MYBPC3: Hazard Ratio 18.5 (95% CI 2.31, 148), p=0.006. Applying HCM Risk-SCD calculator, model had better predictive discrimination when variable "causal variant in gene other than MYBPC3" was added in multivariate analysis, with high-risk category &amp;gt;=6% (C-statistic =0.931 vs 0.844) and intermediate-risk category 4-6% (C-statistic =0.845 vs 0.514). Same occurred with ESC Guidelines algorithm, adding that variable to 2 risk factors category (C-statistic =0.881 vs 0.742) or 1 risk factor (C-statistic =0.844 vs 0.635). HCM Risk-Kids also improved its predictive discrimination adding the genetic value to high-risk category &amp;gt;=6% (C-statistic =0.896 vs 0.796) and intermediate-risk (C-statistic =0.821 vs 0.506). Conclusions Genotype may have prognostic value in SCD risk in HCM in children. Our results suggests that causal genetic variants in genes other than MYBPC3 can lead to higher risk of SCD. Genetic information might be considered for future models of arrhythmic risk in children with HCM.

Diagnostic Accuracy Performance of Fluorescence In Situ Hybridization (FISH) for Biliary Strictures: A Systematic Review and Meta-Analysis

Background and Aims: This systematic review and meta-analysis aims to compare the performance of UroVysion® FISH based on the different definitions of a positive result used in published literature with the goal of determining the optimal FISH definition for detecting pancreaticobiliary malignancy. Methods: A systematic literature search identified studies from database inception to Sept 2024 that evaluated the diagnostic performance of FISH in determining malignancy among patients with biliary strictures. All thresholds for positive FISH, as defined by the individual study, were included in this review. Subgroup analysis was performed based on the definitions of positive FISH as follows: (1) polysomy only; (2) polysomy, tetrasomy, or trisomy; and (3) polysomy or 9p deletion. Results: Eighteen studies comprising 2516 FISH specimens were analyzed, including 1133 (45.0%) with malignancy. Using a threshold for positivity as defined in individual studies, the overall sensitivity of FISH was 57.6% (95% confidence interval [CI], 49.4–65.4%), and the overall specificity was 87.8% (95% CI, 79.2–93.2%). Subgroup analysis showed that polysomy as the threshold for positive FISH yielded a sensitivity of 49.4% (95% CI, 43.2–55.5%), with an increased specificity of 96.2% (95% CI, 92.7–98.1%), while polysomy + tetrasomy/trisomy as positive FISH resulted in an increased sensitivity of 64.3% (95% CI 55.4–72.2%) but a decreased specificity of 78.9% (95% CI 64.4–88.5%). The addition of 9p deletion to polysomy as the criteria for a positive test resulted in a non-significant increase in sensitivity (54.7% (95% CI 42.4–66.5%) while maintaining specificity (95.1% (95% CI 84.0–98.6%). Conclusions: Based on these findings, polysomy only or polysomy/9p deletion should be considered as the criterion for defining a positive FISH test to improve diagnostic sensitivity while maintaining high specificity.

The prognostic value of contrast stress echocardiography in a real-world population of symptomatic patients without known coronary artery disease

Abstract Background Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. In addition to diagnosis, non-invasive tests may also provide prognostic information useful in the risk stratification and management of CAD patients. Stress echocardiography (SE) is an accurate, non-invasive method for the detection of obstructive CAD. However, in real-world clinical practice the test performance may vary among different centres, depending on availability, local protocols, and operator expertise. Purpose To evaluate the prognostic value of contrast SE in a real-world population of symptomatic patients without known CAD. Methods This was a cohort follow-up study of patients without known CAD and symptoms of atypical chest pain, unexplained dyspnoea or palpitations who were referred to the echocardiography lab of a tertiary hospital for SE between January 2020 and December 2021. Patients with resting regional wall motion abnormalities were excluded. All patients underwent treadmill exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) if unable to exercise. Contrast agents were used in almost all patients (99%). The study population was followed-up for at least 2 years after SE by phone and/or electronic hospital records. Cardiac outcome was defined as anatomically or functionally significant stenosis on angiography, revascularization, acute coronary syndrome (ACS), or cardiac-related death. Results The study comprised 266 patients (mean age 58±12 years, 63% male) who underwent either ESE (58%) or DSE (42%). The patients' details are reported in Table 1. The most common indication for the exam was atypical chest pain, with a prevalence of 73%. SE exams were positive for inducible ischaemia in 14 (5%) patients. Symptoms during the exam were present in 3 (21%) patients with positive SE and 4 patients (2%) with negative SE (p=0.004). No serious complications (sustained ventricular tachycardia, myocardial infarction, or death) were recorded. During the follow-up (median 30, IQR 23–38 months), 264 patients (99%) were successfully contacted. Cardiac outcome occurred in 10 patients. Among 14 patients with positive SE, 8 underwent revascularization due to significant coronary artery stenosis. Among 250 patients with negative SE, 1 underwent revascularization due to significant coronary artery stenosis and 1 presented with ACS 13 months after the test (both patients underwent DSE). Negative predictive value was 99% over a median follow-up of 30 months, corresponding to an annualized event rate of 0.32% per year. A positive SE was significantly associated with cardiac outcome (log-rank test p&amp;lt;0.0001, Figure 1). Conclusion Contrast SE carries significant prognostic implications in symptomatic patients without known CAD. A positive test is strongly associated with the need for revascularization, while a normal test result has an excellent negative predictive value regarding cardiovascular morbidity and mortality.Figure 1

Participation rate and yield of indirect cascade genetic screening for familial hypercholesterolemia using a web-based communication platform (CATCH): a randomized multicenter implementation trial

Abstract Introduction Cascade genetic screening for familial hypercholesterolemia (FH) is poorly performed when direct contact with relatives by health professionals is not allowed. We aimed to compare the effectiveness of implementing a web-based communication platform in a large-scale cascade genetic screening program for FH, while maintaining the confidentiality of indirect family contacts. Methods The CATCH study is a prospective randomized open-label multicenter implementation trial that promotes family cascade genetic screening in Swiss adults older than 16 years with a newly diagnosed pathogenic variant for FH. Each family was randomly assigned to a multigenerational indirect cascade genetic screening (1:1) either via the possibility to use of a web-based platform designed to send pre-prepared text messages or emails, and allowing to connect to a specialized clinical center, or a cascade genetic screening via the local recommended procedure. The primary outcome was the 6-month participation rate of relatives, defined as the number of genetic tests performed within 6 months after referral, over the number of eligible relatives for screening, i.e. living first-degree relatives aged 5 years or older. The secondary outcome was the 6-month yield of positive genetic tests, defined as the number of positive tests over the number of eligible relatives. Both outcome estimates were obtained after accounting for family clusters. Results Between 11/20 and 12/23, we enrolled 221 adults with a phenotype of FH for genetic testing, with 87 of them having confirmed genetic FH, corresponding to a total of 401 eligible relatives for cascade screening, with 102 relatives eventually undergoing genetic testing. Among the 87 index cases with genetic FH, 44 were randomly assigned to the web-based platform screening, and 43 were assigned to the local procedure screening. The 6-month participation rate of relatives was 71 of the 218 eligible relatives (29% [95% CI 21–38]) for the web-based platform screening, and 31 of the 183 eligible relatives (14% [95% CI 8–23]) for the local procedure screening (odds ratio (OR) 2.46 [95% CI 1.22–4.98]), p=0.012) (Figure). Similarly, the yield of detection of positive relatives was higher for the web-based platform screening, (16% [95% CI 11–23]) compared to the local procedure screening (7% [95% CI 4–13]), with OR of 2.43 [95% CI 1.11–5.30], p=0.026. Among the 55 positive relatives identified with genetic FH within 6-months, 13.0% were younger than 18 years, 25.5% were current smokers, and 56.0% were not using any lipid-lowering drugs. Conclusions The effectiveness of cascade genetic screening for FH was approximately doubled by integrating a web-based platform that facilitates family communication and access to specialized clinical centers. Modern communication technology is well suited to be integrated in large-scale indirect genetic screening programs to increase the early identification of patients at high cardiovascular risk.

Coronary artery disease screening in renal transplant candidates: insights from a large prospective cohort

Abstract Background There is currently no specific consensus regarding the screening strategy for CAD in renal transplant candidates. Purposes To describe in renal transplant candidates 1/ Strategies and results of CAD screening and 2/ renal and cardiovascular outcomes in this population Methods All patients registered on kidney transplant waiting list in our tertiary centre were classified into no screening for CAD (unscreened), screened, or with prior CAD. Unscreened was defined as no ischemia or anatomic testing while on waiting list or within the year prior to listing. Screening was considered as "positive" when it led to diagnostic of obstructive CAD (stenosis &amp;gt; 50%). Primary outcome was a composite outcome defined as [death or unplanned revascularization]. Primary outcome and renal transplant were analysed using multivariable Cox model. Results From 2005 to 2023, 3248 patients were registered as candidates for kidney transplantation, 228 (7.0%) patients had a history of CAD, 1987 (61.2%) patients were screened for CAD and 1033 (31.8%) were unscreened. Initial screening investigation were mainly stress cardiovascular MRI (33.7%), stress TTE (27.7%) or myocardial perfusion imaging (26.4%). Among screened patients, 133 (6.7%) patients had a positive screening for obstructive CAD. Within 4.7 [1.2 – 7.2] years, using patients with a negative screening as a reference, patients with positive screening and known CAD were less likely to receive renal transplant (aHR 0.70 [0.53 ; 0.93] and 0.64 [0.49 ; 0.84] respectively), while patients without screening were similarly transplanted (aHR 1.01 [0.89 ; 1.15]). Patients without screening or with a prior history of CAD were at higher risk of primary outcome compared with patients with negative screening (aHR 1.49 [1.16; 1.91]) and aHR 1.97 [1.48; 2.62] respectively), along with patients on dialysis at registration (1.37 [1.13; 1.66]), diabetic patients (1.79 [1.47; 2.18]) and smokers (1.25 [1.03; 1.53]). Age was an interaction factor between unscreening and primary outcome, as there was no association in younger patients (aHR 1.21 [0.81; 1.81]). Conclusion Among candidates for kidney transplantation, 2 out of 3 patients underwent non-invasive testing for obstructive CAD resulting in less than 10 % of positive cases. Positive testing and history of CAD were associated with a lower opportunity for kidney transplantation compared with negative testing or absence of screening. Nonetheless, absence of screening was associated with a higher risk of [death + unplanned revascularization], especially in older patients.Central illustration

Machine learning methods for diagnostic disease prediction and treatment decisions in parvovirus B19 positive viral cardiomyopathy

Abstract Background Parvovirus B19 (B19V) is the most common type of virus found in endomyocardial biopsies (EMB) from patients with inflammatory heart disease. However, the detection of genomic B19V-DNA appears to have little clinical significance and is often considered an incidental finding. Recent analyses of a large cohort of B19V-positive patients revealed that the detection of RNA transcripts rather than DNA is of clinical importance, as B19V-RNA-positive patients have a significantly worse cardiovascular outcome. Here, we applied machine learning (ML) methods to assess the impact of B19V transcriptional activity on cardiac inflammation and patient clinical outcome. Methods and results A total of 305 patients with a known clinical course and a positive endomyocardial B19V-DNA test were included in this study. Follow-up measurements of the B19V-specific transcripts VP1/2 and NS1 revealed significantly worse clinical courses than in patients without B19V-RNA detection (P=0.019, hazard ratio (95% CI)=1.62 (1.10-2.57)). LVEF at follow-up was significantly lower in patients with detected B19V-RNA (P=0.007), and adverse events such as worsening LV function (P=0.003) or stable systolic dysfunction (P=0.013) were more frequent in this group. Importantly, analysis of inflammatory markers in EMB showed no difference in patients with and without RNA detection (P=0.432), suggesting that the deterioration in clinical outcome was related to B19V transcriptional activity rather than an increase in inflammation. The analysis of area under the receiver operating characteristic curve (AUROC) of B19V-RNA-negative patients revealed that the macrophage marker MAC-1 (AUROC=0.66, P=0.002) was the single most prognostically relevant parameter, while the T cell marker CD3 (AUROC=0.73, P&amp;lt;0.001) was identified as the most prognostically relevant marker in B19V-RNA-positive patients. The linear combination of several inflammatory markers increased the AUROC value to 0.67 in B19V-RNA-negative patients and to 0.74 in B19V-RNA-positive patients. To further increase prognostic accuracy, we trained ML models on features derived from EMB inflammatory markers. For the prediction of major adverse cardiac events within 60 months, the best ML-models achieved an AUROC of 0.87 in B19V-RNA-positive and of 0.86 in B19V-RNA-negative patients, while models that neglect the differentiation of patients with regard to the presence of B19V RNA transcripts only achieved an AUROC of up to 0.76. Conclusions These results show that B19V transcriptional activity is an independent risk marker for adverse cardiac events in patients with viral cardiomyopathy and thus confirm the clinical-therapeutic importance of myocardial biopsy. Furthermore, we present an ML-based algorithm that accurately indicates disease progression in B19V-positive cardiomyopathy patients and is thus helpful for appropriate therapy recommendation.

Epidemiological, clinical, paraclinical, evolutionary, and therapeutic aspects of hypertensive patients infected by COVID-19: about 702 patients in our city

Abstract Introduction Hypertension (HT) is a major cardiovascular risk factor frequently observed in COVID-19 patients. This study aimed to determine the frequency of hypertensive patients infected with COVID-19 at a national hospital, describe their epidemiological, clinical, paraclinical, and therapeutic profile, their disease progression, and identify factors associated with death. Methodology A retrospective, descriptive, and analytical study was conducted over 24 months and 4 days, from 27 March 2020 to 30 March 2022, at national hospital. Included were hospitalized patients at a hospital with a confirmed COVID-19 diagnosis, known hypertensives, regardless of gender, and with a hospitalization record. COVID-19 diagnosis was based on a positive SARS-CoV-2 RT-PCR or a positive COVID Rapid Diagnostic Test. Data were collected using a survey form, with a p-value less than 0.05 considered statistically significant for bivariate analysis. Results The study enrolled 702 patients, a hospital frequency of 23.95%. The average age was 65.14 ± 12.24 years with a sex ratio of 0.81. Comorbidities were predominantly diabetes (40.5%) and dyslipidemia (4.8%). Common symptoms included cough (65%), dyspnea (42.3%), fever (47.4%), and asthenia (35.9%). Blood pressure was normal in 15.2%, high-normal in 16.8% of patients. HT was Grade I in 12.1%, Grade II in 10%, and Grade III in 6.8% of the population, with blood pressure unmeasurable in 0.3% of known hypertensive patients. SARSCOV2 infection was mild in 34.2% and moderate in 42.8% of cases. CT scans showed extensive (31.8%), severe (25.9%), moderate (25.6%), critical (8.5%), and minimal (7.9%) lung damage. Treatment mainly consisted of ACE inhibitors (29%), ACE inhibitors in combination with another antihypertensive (8.4%), and ARBs in combination with an antihypertensive (). The average hospital stay was 12.85 days with a favorable outcome in 81% and a mortality rate of 15.5%. Factors associated with death included not being vaccinated against COVID-19 (HR: 11.70; 95% CI: 1.324-103.519), critical clinical form (HR: 11.70; 95% CI: 1.324-103.519), pulmonary consolidation (HR: 8.87; 95% CI: 7.539-24.207), high creatinine (HR: 4.69; 95% CI: 1.360-16.181), critical CT thoracic level (HR: 2.42; 95% CI: 1.020-5.745), and not taking ARBs (HR: 6.02; 95% CI: 2.812-12.889). Conclusion HT can be associated with COVID-19, impacting the disease's prognosis with significant mortality. Preventing its incidence and morbidity/mortality is crucial.

Iron status in children with acute COVID-19 and paediatric inflammatory multisystem syndrome during infection and after recovery

BackgroundCOVID-19 has significant effects on organ function, particularly on lung function and iron metabolism. Studies have shown increased levels of ferritin, an iron storage protein, in COVID-19 patients, indicating potential changes in iron utilization. Research has focused primarily on adults, with limited studies on paediatric patients and a lack of comparisons with MIS-C patients. This study aimed to assess iron status in paediatric COVID-19 patients using traditional and new biomarkers, soluble transferrin receptors (sTfR) and Reticulocyte hemoglobin equivalent (RET-He), to improve diagnosis and prognosis. Additionally, we sought to compare iron status between acute COVID-19 patients and MIS-C patients and evaluate the relationships among iron dysmetabolism, disease severity, and prognosis in paediatric patients. The study also involved monitoring iron status during and after infection to understand its impact on patient severity and prognosis.MethodsA cohort study involving 49 patients aged 1 month to 18 years was conducted at the isolation department of Mansoura University Children's Hospital. The study included 36 patients with acute COVID-19 and 13 with multisystem inflammatory syndrome of childhood (MIS-C). Diagnosis was based on PCR from a deep nasopharyngeal swab or a positive antibody test. Follow-up of survivors was conducted 3 months after recovery. Blood samples were obtained during infection and at follow-up for CBC, Ret-He, iron kinetics, and sTfR analyses.ResultsSignificant iron deficiency anaemia was observed in all patients during infection, with improvement after 3 months of recovery in survivors. The improvement was more obvious in MIS-C patients, with Hb and iron kinetics not significantly affected by disease severity. The STfR was significantly lower in nonsurvivors than in survivors. The ROC curve showed that a baseline sTfR ≤ 18 nmol/L was a statistically significant difference between nonsurvivors and survivors (area under the curve (AUC) = 0.810, p < .001), with 66.7% sensitivity and 82.5% specificity. Regression analysis revealed that patients with baseline sTfRs ≤ 18 nmol/L were 5.9 times more susceptible to death.ConclusionThis study revealed that COVID-19 in children caused iron deficiency anaemia, which improved within 3 months after recovery. Haemoglobin and sTfRs were identified as reliable indicators of IDA in these patients, unlike iron kinetics and RET-He.